• Title/Summary/Keyword: Dose-response Relationship

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A comparison of metabolomic changes in type-1 diabetic C57BL/6N mice originating from different sources

  • Lee, Seunghyun;Kwak, Jae-Hwan;Kim, Sou Hyun;Yun, Jieun;Cho, Joon-Yong;Kim, Kilsoo;Hwang, Daeyeon;Jung, Young-Suk
    • 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.

Effects of NaF Contents on the NEFA and Uric Acid Concentrations in Rats (NaF 첨가량이 흰쥐의 NEFA 및 Uric Acid 농도에 미치는 영향)

  • Kim, Han-Soo
    • Journal of the Korean Applied Science and Technology
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    • v.38 no.5
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    • pp.1282-1291
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    • 2021
  • The aim of this study was to investigate the hematology and serum chemistry values on Sprague-Dawley rats, used sodium fluoride (NaF) for 5 weeks. Seven-week-old male rats were divided into nine groups and fed experimental diets with oral NaF treatment, basal diet group (BG), basal diet plus oral NaF groups (NF3~NF50). Concentrations of non-esterified fatty acid (NEFA), blood urea nitrogen (BUN), creatinine, uric acid in serum were significantly higher in the oral NaF groups than BG (𝛼=0.05). Total calcium (T-Ca) and phosphorus (Pi) concentrations was observed to be significant difference, it was decreased with an increase in the NaF levels (𝛼=0.05). Accordingly, sodium fluoride exposures and dose-response relationship, which was found on the bad influences in hematology. Such association is considered that the long-term fluoride exposure caused nephrotoxicity.

Relationship between psychological distress and the adherence to the Korean healthy eating index (KHEI): the Korea National Health and Nutrition Examination Survey (KNHANES) 2013 and 2015

  • Yoon, Yeong Sook;Oh, Sang Woo
    • Nutrition Research and Practice
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    • v.15 no.4
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    • pp.516-527
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    • 2021
  • BACKGROUND/OBJECTIVES: This study examined the association of depressive symptoms, stress perception, and suicidal ideation with overall dietary quality using the newly developed Korean healthy eating index (KHEI). SUBJECTS/METHODS: This study included 9,607 adults (3,939 men and 5,668 women, ≥ 19 years) who participated in the 6th Korea National Health and Nutrition Examination Survey 2013 and 2015. The KHEI scores were calculated using the food frequency questionnaire data. Survey logistic regression analyses were performed to analyze the association between psychiatric distress and dietary quality. RESULTS: The percentage of subjects with experience of depressive mood, higher stress perception, and suicidal ideation was 8.2%, 25.0%, and 3.7% in men and 15.4%, 27.3%, and 6.0% in women, respectively. The mean KHEI score was 61.5 ± 0.29 in men and 64.8 ± 0.24 in women (P < 0.001). The present study found a difference in the adherence to specific dietary components of the KHEI between sexes. Men experiencing depressive symptoms were less likely to eat meat, fish, eggs, and beans, while depressed women showed lower vegetable intake. Both men and women with suicidal ideation showed a lower intake of vegetables. The men with stress had a lower breakfast eating score than those without stress (7.21 vs. 6.77, P = 0.016). The multivariate-adjusted odds ratios for depressive symptoms, stress perception, and the suicidal idea in women with the highest quartile of KHEI scores compared to the lowest quartile was 0.69 (95% confidence interval, 0.51-0.92), 0.73 (0.58-0.82), and 0.52 (0.33-0.82), respectively and significant dose-response associations were observed (P for trends < 0.05 for all). On the other hand, these associations were not observed in men after adjusting for the confounding variables (P for trends > 0.05 for all). CONCLUSIONS: Poor adherence to dietary recommendations is associated with psychological distress, especially in women.

The Association Between PM2.5 Exposure and Diabetes Mellitus Among Thai Army Personnel

  • Apisorn Laorattapong;Sarun Poobunjirdkul;Thanapoom Rattananupong;Wiroj Jiamjarasrangsi
    • Journal of Preventive Medicine and Public Health
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    • v.56 no.5
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    • pp.449-457
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    • 2023
  • Objectives: This study investigated the association between baseline exposures to particulate matter with a diameter <2.5 microns (PM2.5) and subsequent temporal changes in PM2.5 exposure with the incidence of type 2 diabetes among Royal Thai Army personnel. Methods: A retrospective cohort study was conducted using nationwide health check-up data from 21 325 Thai Army personnel between 2018 and 2021. Multilevel mixed-effects parametric survival statistics were utilized to analyze the relationship between baseline (i.e., PM2.5-baseline) and subsequent changes (i.e., PM2.5-change) in PM2.5 exposure and the occurrence of type 2 diabetes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were employed to assess this association while considering covariates. Results: There was a significant association between both PM2.5 baseline and PM2.5-change and the incidence of type 2 diabetes in a dose-response manner. Compared to quartile 1, the HRs for quartiles 2 to 4 of PM2.5-baseline were 1.11 (95% CI, 0.74 to 1.65), 1.51 (95% CI, 1.00 to 2.28), and 1.77 (95% CI, 1.07 to 2.93), respectively. Similarly, the HRs for quartiles 2 to 4 of PM2.5-change were 1.41 (95% CI, 1.14 to 1.75), 1.43 (95% CI, 1.13 to 1.81) and 2.40 (95% CI, 1.84 to 3.14), respectively. Conclusions: Our findings contribute to existing evidence regarding the association between short-term and long-term exposure to PM2.5 and the incidence of diabetes among personnel in the Royal Thai Army.

Presenteeism and Traffic Accident Among Taxi Drivers: A Prospective Cohort Study in Japan

  • Makoto Okawara;Kei Tokutsu;Keiki Hirashima;Tomohiro Ishimaru;Yoshihisa Fujino
    • Safety and Health at Work
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    • v.15 no.2
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    • pp.208-212
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    • 2024
  • Background: Traffic accidents involving professional drivers have serious societal repercussions. Unique occupational stressors and health risks exacerbate the likelihood of traffic accidents among professional drivers. This study explores the association between presenteeism-impaired work performance due to working while unwell-and traffic accident risk among professional taxi drivers in Japan. Methods: A prospective cohort study was conducted from June 2022 to February 2023, involving taxi drivers from a single company in Fukuoka Prefecture, Japan. Presenteeism was assessed using the Work Functioning Impairment Scale (WFun). Primary outcome involved the number of self-reported minor traffic accidents. The incidence rate ratio (IRR) of minor traffic accident occurrences was estimated using a Poisson regression analysis, adjusted for confounders including sex, age, and driving experience. Results: Of 838 targeted drivers, 435 were included in the analysis. Higher baseline work functioning impairment was associated with a significant trend of increasing IRR of minor traffic accidents (p for trend = 0.045). A dose-response relationship was seen between the degree of presenteeism and incidence rate of minor traffic accidents. Conclusion: Higher levels of presenteeism were associated with an increased risk of traffic accidents among taxi drivers. The findings underscore the need for socio-economic support and prioritized health management to mitigate traffic accident risk among professional drivers. This study highlights the importance of managing non-critical health issues alongside serious health conditions for safer driving practices among professional drivers in Japan.

Dosimetric and Clinical Predictors of Acute Esophagitis in Lung Cancer Patients in Turkey Treated with Radiotherapy

  • Etiz, Durmus;Bayman, Evrim;Akcay, Melek;Sahin, Bilgehan;Bal, Cengiz
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.7
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    • pp.4223-4228
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    • 2013
  • Background: The purpose of this study was to determine the clinical and dosimetric factors associated with acute esophagitis (AE) in lung cancer patients treated with conformal radiotherapy (RT) in Turkey. Materials and Methods: In this retrospective review 104 lung cancer patients were examined. Esophagitis grades were verified weekly during treatment, and at 1 week, and 1 and 2 months afterwards. The clinical parameters included patient age, gender, tumor pathology, number of chemotherapy treatments before RT, concurrent chemotherapy, radiation dose, tumor response to RT, tumor localization, interruption of RT, weight loss, tumor and nodal stage and tumor volume. The following dosimetric parameters were analyzed for correlation of AE: The maximum ($D_{max}$) and mean ($D_{mean}$) doses delivered to the esophagus, the percentage of esophagus volume receiving ${\geq}10$ Gy ($V_{10}$), ${\geq}20$ Gy ($V_{20}$), ${\geq}30$ Gy ($V_{30}$), ${\geq}35$ Gy ($V_{35}$), ${\geq}40$ Gy ($V_{40}$), ${\geq}45$ Gy ($V_{45}$), ${\geq}50$ Gy ($V_{50}$) and ${\geq}60$ Gy ($V_{60}$). Results: Fifty-five patients (52.9%) developed AE. Maximum grades of AE were recorded: Grade 1 in 51 patients (49%), and Grade 2 in 4 patients (3.8%). Clinical factors had no statistically significant influence on the incidence of AE. In terms of dosimetric findings, correlation analyses demonstrated a significant association between AE and $D_{max}$ (>5117 cGy), $D_{mean}$ (>1487 cGy) and $V_{10-60}$ (percentage of volume receiving >10 to 60 Gy). The most significant relationship between RT and esophagitis were in $D_{max}$ (>5117 cGy) (p=0.002) and percentage of esophageal volume receiving >30 Gy ($V_{30}$ >31%) (p=0.008) in the logistic regression analysis. Conclusions: The maximum dose esophagus greater than 5117 cGy and approximately one third (31%) of the esophageal volume receiving >30 Gy was the most statistically significant predictive factor associated with esophagitis due to RT.

Four-week Repeated Oral Toxicity Study of the Extract of Aralia elata in Rats (랫드에서 두릅 추출물의 4주 반복투여 독성시험)

  • Jin, Ju-Youn;Yang, Hee-Kyoung;Kim, Ji-Min;Ko, Mun-Su;Hong, Hyun-Ju;Jin, Young-Gun;Kim, Dong-Gun;Kim, Sang-Chul;Lee, Il;Hyon, Min-Kyong;Kang, Sang-Chul;Kim, Jae-Hoon;Lee, Young-Jae
    • Toxicological Research
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    • v.22 no.4
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    • pp.445-452
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    • 2006
  • Aralia elata, a common medicinal and culinary herb, has beer consumed for centuries without any reported adverse effects. However, due to its limited safety information, we decided to investigate the repeated-dose toxicity of ethanolic extract of Aralia elata. The test was administered once daily by the gavage to male and female rats at doses of 0, 250, 500 and 1,000 mg/kg/day for four weeks. Throughout the study, no treatment-related deaths or clinical signs were observed. Also, no apparent changes were detected in ophthalmoscopy, urinalysis, serum biochemistry, hematology and gross necropsy. The test result showed a significant decrease in body and heart weight of males treated with 250 mg/kg of extract of Aralia elata compared to normal control, a significant increase in relative brain weight and adrenal weight in females treated with 250 mg/kg of extract compared to normal control. However, all these changes were not considered toxicologically important due to irrelevant dose-response relationship to gross and microscopic findings. Histopathologically, abnormal changes were not observed in any target organs. On the basis of these results, the NOAEL of extract of Aralia elata was estimated to be more than 1,000 mg/kg/day under the tested conditions.

The Effects of Alkaloid Fraction of Korean Ginseng on the Radiation-Induced DNA Strand Breaks (방사선 조사에 의한 DNA Double Strand Breaks의 생성 및 회복에 미치는 인삼 알칼로이드 분획의 효과)

  • Cho Chul Koo;Kim Tae Hwan;Yoo Seong Yul;Koh Kyoung Hwan;Kim Mi Sook;Kim Jeong Hee;Kim Seong Ho;Yoon Hyung Keun;Ji Young Hoon
    • Radiation Oncology Journal
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    • v.13 no.2
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    • pp.113-120
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    • 1995
  • Purpose : To investigate the effect of alkaloid fraction from Korean ginseng on radiation-induced DNA double strand breaks (dsb) formation and repair in murine lymphocytes Materials and Methods : We used the neutral filter elution technique to assay $^{60}Co\;{\gamma}$ ray-induced DNA double strand breaks formation and repair in C57BL/6 mouse spleen lymphocytes for evaluating the dose-response relationship in the presence of alkaloid fraction as a radioprotective agent. The lymphocytes were stimulated with Phytohemagglutinin (PHA, 2 u g/ml) to label $^3[H]-thymidine.$ Isotope-labelled lymphocytes in suspension were exposed to 100 Gy at $0^{\cdot}C$ in the alkaloid fraction-treated group and elution procedure was performed at PH 9.6. The extents of formation of radiation-induced DNA double strand breaks and repair were compared respectively via strand scission factor (SSF) and relative strand scission factor (RSSF). Results: Alkaloid fraction reduced the formation of double strand breaks with dose modification factor of 2 15, compared to control group Rejoining of DNA dsb appeared to take place via two components. The first fast component was completed within 20.4 minutes, but the second slow component was not completed until 220.2 minutes after irradiation. About $30\%$ of dsb formed by irradiation was ultimately unrejoined despite the administration of alkaloid fraction. The administration of alkaloid fraction had a great effect on the second slow component of repair; the half-time of fast component repair was not changed, but that of slow component was 621.8 minutes. Conclusion: Neutral filter elution assay Proved to be a very effective method to quantitate the extents of DNA dsb formation and its repair. By using this technique, we were able to evaluate the efficiency of alkaloid fraction from Korean ginseng as a valuable radioprotector. Alkaloid fraction can be used prophylactically to prevent or ameliorate the severe radiation damages in workers and neighbors around the atomic power plants. For more refined study, however, more advanced purification of alkaloid fraction wil be needed in the near future.

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A Parametric Study of Pulsed Gamma-ray Detectors Based on Si Epi-Wafer (실리콘 에피-웨이퍼 기반의 펄스감마선 검출센서 최적화 연구)

  • Lee, Nam-Ho;Hwang, Young-Gwan;Jeong, Sang-Hun;Kim, Jong-Yeol;Cho, Young
    • Journal of the Korea Institute of Information and Communication Engineering
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    • v.18 no.7
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    • pp.1777-1783
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    • 2014
  • In this paper, we designed and fabricated a high-speed semiconductor sensor for use in power control devices and analyzed the characteristics with pulsed radiation tests. At first, radiation sensitive circular Si PIN diodes with various diameters(0.1 mm ~5.0 mm) were designed and fabricated using Si epitaxial wafer, which has a $42{\mu}m$ thick intrinsic layer. The reverse leakage current of the diode with a radius of 2 mm at a reverse bias of 30 V was about 20.4 nA. To investigate the characteristic responses of the developed diodes, the pulsed gamma-radiation tests were performed with the intensity of 4.88E8 rad(Si)/sec. From the test results showing that the output currents and the rising speeds have a linear relationship with the area of the sensors, we decided that the optimal condition took place at a 2 mm diameter. Next, for the selected 2 mm diodes, dose rate tests with a range of 2.47E8 rad(Si)/sec to 6.21E8 rad(Si)/sec were performed. From the results, which showed linear characteristics with the radiation intensity, a large amount of photocurrent over 60mA, and a high speed response under 350ns without saturation, we can conclude that the our developed PIN diode can be a good candidate for the sensor of power control devices.

Effect of remifentanil on intraoperative fluid balance: a retrospective statistical examination of factors contributing to fluid balance

  • Ohara, Sayaka;Nishimura, Akiko;Tachikawa, Satoshi;Iijima, Takehiko
    • Journal of Dental Anesthesia and Pain Medicine
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    • v.20 no.3
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    • pp.129-135
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    • 2020
  • Background: Postoperative fluid retention is a factor that causes delay in recovery and unexpected adverse events. It is important to prevent intraoperative fluid retention, which is putatively caused by intraoperative release of stress hormones, such as ADH (anti-diuretic hormone) or others. We hypothesized that intraoperative analgesia may prevent pathological fluid retention. We retrospectively explored the relationship between analgesics and in-out balance in surgical patients from anesthesia records. Methods: Anesthetic records of 80 patients who had undergone orthognathic surgery were checked in this study. Patients were anesthetized with either TIVA (propofol and remifentanil) or inhalational anesthesia (sevoflurane and remifentanil). During surgery, acetated Ringer's solution was infused for maintenance at a rate of 3-5 ml/kg/h at the discretion of the anesthetist. The perioperative parameters, including the amount of crystalloid and colloid infused, and the amount of urine and bleeding were checked. Furthermore, we checked the amount and administration rate of remifentanil during the surgical procedure. The correlation coefficient between the remifentanil dose and the in-out balance or the urinary output was analyzed using the Pearson correlation coefficient. The contributing factor to fluid retention, including urinary output, was statistically examined by means of multivariate logistic regression analysis. Results: A significant positive correlation was found between remifentanil dose and urinary output. Urinary output less than 0.04 ml/kg/min was suggested to cause positive fluid balance. Although in-out balance approaches zero balance with increase in remifentanil administration rate, no contributing factor for near-zero fluid balance was statistically picked up. The remifentanil administration rate was statistically picked up as the significant factor for higher urinary output (> 0.04 ml/kg/min) (OR, 2,644; 95% CI, 3.2-2.2 × 106) among perioperative parameters. Conclusions: In conclusion, remifentanil contributes in maintaining the urinary output during general anesthesia. Although further prospective study is needed to confirm this hypothesis, it was suggested that fluid retention could be avoided through suppressing intraoperative stress response by means of appropriate maintenance of remifentanil infusion rate.