• Title/Summary/Keyword: Low Dose

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Single Oral Dose Toxicity Study of Black Raspberry Extract in Sprague-Dawley Rats (복분자 추출물의 Sprague-Dawley rat를 이용한 단회 경구 투여 독성시험)

  • Lee, Joo Young;Ji, Kon-Young;Song, Kwang Hoon
    • The Korea Journal of Herbology
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    • v.35 no.4
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    • pp.45-50
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    • 2020
  • Objective : This study was performed to evaluate the toxicity after a single oral administration of black raspberry extract to male and female Sprague-Dawley (SD) rats and to determine the approximate lethal dose (ALD). Methods : We previously showed that the black raspberry extract repressed the simvastatin-mediated expression of Proprotein convertase subtilisin/kexin type 9 (PCSK9) and improved Low-Density Lipoprotein cholesterol (LDL-C) uptake by hepatocytes through the induction of the Low-Density Lipoprotein Receptor expression in hepatocytes. The groups consisted of black raspberry extract groups, as an oral dose of 2,000 mg/kg and a control group. 5 weeks SD rats were randomly assigned to 4 groups of 5 rats. Each male and female SD rats were administered orally once. For 14 days after the administration, mortality, clinical signs, changes in body weight, and necropsy findings were observed according to the "Standard for Toxicity Study of Pharmaceuticals" of Korea Food and Drug Administration (KFDA) guideline and "Acute Oral Toxicity- Fixed Dose Procedure" of OECD Test Guideline. Results : There were no cases of mortality in the group administered with 2,000 mg/kg of male and female, and no abnormalities in body weight change and clinical signs. Also, no gross abnormalities were observed at the autopsy. Conclusions : As a result of a single oral administration of the black raspberry extract to SD rats, the ALD was determined to exceed 2,000 mg/kg for both male and female SD rats.

Hershberger Assays for Bisphenol-A and Its Substitute Candidates

  • Kim, Hee-Su;Kim, Yong-Bin;Choi, Donchan;Cheon, Yong-Pil;Lee, Sung-Ho
    • Development and Reproduction
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    • v.21 no.4
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    • pp.441-448
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    • 2017
  • Bisphenol-A(BPA) is a member of alkylphenol family, and shows adverse effects including reduced fertility, reproductive tract abnormalities, metabolic disorder, cancer induction, neurotoxicity and immunotoxicity. In the present study, we conducted Hershberger assay to evaluate whether the two candidates to replace BPA have androgenic or antiandrogenic activity. The assay was carried out using immature castrated Sprague-Dawley male rats. After 7 days of the surgery, testosterone propionate (TP, 0.4 mg/kg/day) and test materials (low dose, 40 mg/kg/day; high dose, 400 mg/kg/day) were administered for 10 consecutive days by subcutaneous (s.c.) injection and oral gavage, respectively. Test materials were BPA, isosorbide (ISO) and cyclohexanedimethanol (CHDM). The rats were necropsied, and then the weights of five androgen-dependent tissues [ventral prostate, seminal vesicle, levator ani-bulbocavernosus (LABC) muscle, paired Cowper's glands, and glans penis] and three androgen-insensitive tissues (kidney, spleen and liver) were measured. All test materials including BPA did not exhibit any androgenic activity in the assay. On the contrary, antiandrogen-like activities were found in all test groups, and the order of the intensity was CHDM > BPA > ISO in the five androgen-sensitive tissues. There was no statistical difference between low dose treatment and high dose treatment of BPA group as well as ISO group. In CHDM group, high dose treatment exhibited most severe weight reduction in all measured tissues. There was no statistical difference in androgen-insensitive tissue measurements, except BPA groups. Since the effects of ISO treatment on the accessory sex organs were much less or not present at all when compared to those of BPA, ISO could be a strong candidate to replace BPA. CHDM treatment brought most severe weight reduction in all of androgen-sensitive tissues, so this material should be excluded for further screening of BPA substitute selection.

Hershberger Assays for Di-2-ethylhexyl Phthalate and Its Substitute Candidates

  • Kim, Hee-Su;Cheon, Yong-Pil;Lee, Sung-Ho
    • Development and Reproduction
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    • v.22 no.1
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    • pp.19-27
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    • 2018
  • In the present study, we employed Hershberger assay to determine possible androgenic or antiandrogenic activities of three di-2-ethylhexyl phthalate (DEHP) substitute candidates. The assay was carried out using immature castrated Sprague-Dawley male rats. After 7 days of the surgery, testosterone propionate (TP, 0.4 mg/kg/day) and test materials (low dose, 40 mg/kg/day; high dose, 400 mg/kg/day) were administered for 10 consecutive days by subcutaneous (s.c.) injection and oral gavage, respectively. Test materials were DEHP, 2-ethylhexyl oleate (IOO), 2-ethylhexyl stearate (IOS) and triethyl 2-acetylcitrate (ATEC). The rats were necropsied, and then the weights of five androgen-dependent tissues [ventral prostate, seminal vesicle, coagulating glands, levator ani-bulbocavernosus (LABC) muscle, paired Cowper's glands, and glans penis] and four androgen-insensitive tissues (kidney, adrenal glands, spleen and liver) were measured. All test materials including DEHP did not exhibit any androgenic activity in the assay. On the contrary, antiandrogen-like activities were found in all test groups, and the order of the intensity was ATEC < DEHP < ISO < IOO in the five androgen-sensitive tissues. There was no statistical difference between low dose treatment and high dose treatment of all replacement candidate groups. In DEHP groups, high dose treatment exhibited significant weight gains in LABC and Glan Penis. There was no statistical difference in androgen-insensitive tissue measurements. Since the effects of ATEC treatment on the accessory sex organs were much less or not present at all when compared to those of DEHP, ATEC could be a strong candidate to replace DEHP. IOO treatment brought most severe weight reduction in all of androgen-sensitive tissues, so this material should be excluded for further screening of DEHP substitute selection.

Effects of the Scattered Radiation on Image Quality and Exposure Dose in Chest Radiography (흉부X선촬영시(胸部X線撮影時) 산란선(散亂線)이 화질(畵質)과 피폭선량(被曝線量)에 미치는 영향(影響))

  • Iino, Yu;Hayashi, Taro;Ishida, Yuji;Maeda, Mika;Sakurai, Tatsua;Lee, Man-Koo;An, Bong-Sun;Kim, Jung-Min
    • Journal of radiological science and technology
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    • v.16 no.2
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    • pp.27-38
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    • 1993
  • To investigate relationships between image guality and exposure dose, Chest X-ray films were evaluated for the following points:how much scattered radiation can affect reduction in image quality and can be permissible diagnostically? For this purpose using a test charts and Burger's phantoms. The visual evaluation of their X-ray films and the measurements of scattered radiation were carried out. The dose of scattered radiation ranging from 20 to 25% was found to be for nothing in any diagnostic obstacle. In this range, surface doses were low of 17, 21, and $25{\mu}Gy$ for The thickness of the chest of 15, 20 and 25 cm respectively. Comparison of these high voltage X-ray films with low voltage ones showed a surface dose rate of 1:11.7. Therefore, X-ray quality, photosensitive materials(film and screen) and grid should be selected very carefully for the purpose of reduction in exposure dose.

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Chronic and Low Dose Exposure to Nonlyphenol or Di(2-Ethylhexyl) Phthalate Alters Cell Proliferation and the Localization of Steroid Hormone Receptors in Uterine Endometria in Mice

  • Kim, Juhye;Cha, Sunyeong;Lee, Min Young;Hwang, Yeon Jeong;Yang, Eunhyeok;Choi, Donchan;Lee, Sung-Ho;Cheon, Yong-Pil
    • Development and Reproduction
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    • v.23 no.3
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    • pp.263-275
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    • 2019
  • Based on our preliminary results, we examined the possible role of low-dose and chronic-exposing of the chemicals those are known as endocrine disrupting chemical (EDC), on the proliferation of uterine endometrium and the localization of steroid receptors. Immunohistochemical or immunofluorochemical methodology were employed to evaluate the localization of antigen identified by monoclonal antibody Ki 67 protein (MKI67), estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2), and progesterone receptor (PGR). In $133{\mu}g/L$ and $1,330{\mu}g/L$ di(2-ethylhexyl) phthalate (DEHP) and $50{\mu}g/L$ nonylphenol (NP) groups, the ratio of MKI67 positive stromal cells was significantly increased but not in $500{\mu}g/L$ NP group. The ratios of MKI67 positive glandular and luminal epithelial cells were also changed by the chronic administration of NP and DEHP in tissue with dose specific manner. ESR1 signals were localized in nucleus in glandular and luminal epithelia of control group but its localization was mainly in cytoplasm in DEHP and NP administered groups. On the other hand, it was decreased at nucleus of stromal cells in $1,330{\mu}g/L$ DEHP group. The colocalization patterns of these nuclear receptors were also modified by the administration of these chemicals. Such a tissue specific and dose specific localization of ESR2 and PGR were detected as ESR1 in all the uterine endometrial tissues. These results show that the chronic lows-dose exposing of NP or DEHP modify the localization and colocalization of ESRs and PGR, and of the proliferation patterns of the endometrial tissues.

Calculation of Shielding Rate and Dose Distribution of Space of L-Block-Type Protective Equipment for Radioactive Fluorine using the Monte Carlo Method (몬테칼로 방법을 이용한 방사성 불소에 대한 L-블럭형 방호장비의 차폐율 및 공간의 선량분포 계산)

  • Han, Dong-Hyun
    • Journal of the Korean Society of Radiology
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    • v.15 no.6
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    • pp.813-819
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    • 2021
  • In this study, the shielding rate of L-block-type shielding equipment used for radiation protection when radioactive fluorine is injected into the human body and the dose distribution of the space in the injection room were calculated using the Monte Carlo method. The shielding rate of the body and window parts of the L-block-type shielding equipment was 99.99%. The dose distribution calculated at a distance of 1 m was relatively high at 135°, 45°, 225°, 315°, and 180° of the XZ plane, and was calculated to be very low at 0°, 90°, and 270°. In the YZ plane, it was relatively high at 135°, 180°, and 225°, and was calculated very low at the remaining angles. The AZ and BZ planes also showed similar results to the YZ plane. In addition, it was confirmed that the shielding rate was the best in the range of 225° to 315° through the dose distribution in the horizontal direction of the source and the 45° direction above the source. These results can be used as basic data necessary for radiation protection of radiation workers.

Metabolomics Approach to Explore the Effects of Rebamipide on Inflammatory Arthritis Using Ultra Performance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry

  • Moon, Su-Jin;Lee, Soo Hyun;Jung, Byung-Hwa;Min, Jun-Ki
    • Journal of Rheumatic Diseases
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    • v.24 no.4
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    • pp.192-202
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    • 2017
  • Objective. Rebampide is a gastroprotective agent used to treat gastritis. It possesses anti-inflammatory and anti-arthritis effects, but the mechanisms of these effects are not well understood. The objective of this study was to explore mechanisms underlying the therapeutic effects of rebamipide in inflammatory arthritis. Methods. Collagen-induced arthritis (CIA) was induced in DBA/1J mice. DBA/1J mice were immunized with chicken type II collagen, then treated intraperitoneally with rebamipide (10 mg/kg or 30 mg/kg) or vehicle (10% carboxymethylcellulose solution) alone. Seven weeks later, plasma samples were collected. Plasma metabolic profiles were analyzed using ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry-based metabolomics study and metabolite biomarkers were identified through multivariate data analysis. Results. Low dose rebamipide treatment reduced the clinical arthritis score compared with vehicle treatment, whereas high dose rebamipide in CIA aggravated arthritis severity. Based on multivariate analysis, 17 metabolites were identified. The plasma levels of metabolites associated with fatty acids and phospholipid metabolism were significantly lower with rebamipide treatment than with vehicle. The levels of $15-deoxy-^{{\Delta}12,14}$ prostaglandin J2 and thromboxane B3 decreased only in high dose-treated groups. Certain peptide molecules, including enterostatin (VPDPR) enterostatin and bradykinin dramatically increased in rebamipide-treated groups at both doses. Additionally, corticosterone increased in the low dose-treated group and decreased in the high dose-treated group. Conclusion. Metabolomics analysis revealed the anti-inflammatory effects of rebamipide and suggested the potential of the drug repositioning in metabolism- and lipid-associated diseases.

Improved postoperative recovery profile in pediatric oral rehabilitation with low-dose dexmedetomidine as an opioid substitute for general anesthesia: a randomized double-blind clinical trial

  • Naveen, Naik B;Jaiswal, Manoj Kumar;Ganesh, Venkata;Singh, Ajay;Meena, Shyam Charan;Amburu, Vamsidhar;Soni, Shiv Lal
    • Journal of Dental Anesthesia and Pain Medicine
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    • v.22 no.5
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    • pp.357-367
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    • 2022
  • Background: Low-dose dexmedetomidine may be a suitable alternative to opioids for pediatric ambulatory procedures under general anesthesia (GA). However, the recovery profile remains unclear. Herein, we aimed to evaluate the effects of low-dose dexmedetomidine on the recovery profile of children. Methods: Seventy-two children undergoing ambulatory oral rehabilitation under GA were randomly and equally distributed into two groups (D and F). Group D received an infusion of dexmedetomidine 0.25 ㎍/kg for 4 min for induction, followed by maintenance of 0.4 ㎍/kg/h. Group F received an infusion of fentanyl 1 ㎍/kg over 4 min for induction, followed by maintenance at 1 ㎍/kg/h. The primary outcome was the extubation time. The secondary outcomes were awakening time, end-tidal sevoflurane (ET-Sevo) requirement, change in hemodynamic parameters, Richmond Agitation-Sedation Scale (RASS), Children's Hospital of Eastern Ontario pain scale (CHEOPS) score, length of PACU stay, and incidence of adverse events. Results: Statistically significant differences were observed in the recovery profile between the groups: the median time for extubation was 3.65 (3.44-6.2) vs. 6.25 (4.21-7) minutes in groups D vs. F (P=0.001), respectively, while the corresponding awakening times were 19 (18.75-21) and 22.5 (22-24) minutes, respectively (P < 0.001). The mean ET-Sevo was low in group D (1.1 vs. 1.2; P < 0.001). The heart rate was significantly low across all time points in group D, without resulting in bradycardia. The median RASS and CHEOPS scores were also significantly lower in group D. No significant differences were observed in the mean arterial pressure, incidence of adverse events, or length of PACU stay. Conclusion: Low-dose dexmedetomidine was more effective than fentanyl as an opioid substitute at providing a better recovery profile in pediatric ambulatory oral rehabilitation under GA. Dexmedetomidine also significantly reduced sevoflurane consumption without causing adverse events or prolonging hospital stay.

Evaluation of Skin Dose and Image Quality on Cone Beam Computed Tomography (콘빔CT 촬영 시 mAs의 변화에 따른 피부선량과 영상 품질에 관한 평가)

  • Ahn, Jong-Ho;Hong, Chae-Seon;Kim, Jin-Man;Jang, Jun-Young
    • The Journal of Korean Society for Radiation Therapy
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    • v.20 no.1
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    • pp.17-23
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    • 2008
  • Purpose: Cone-beam CT using linear accelerator attached to on-board imager is a image guided therapy equipment. Because it is to check the patient's set-up error, correction, organ and target movement. but imaging dose should be cause of the secondary cancer when taking a image. The aim of this study is investigation of appropriate cone beam CT scan mode to compare and estimate the image quality and skin dose. Materials and Methods: Measurement by Thermoluminescence dosimeter (TLD-100, Harshaw) with using the Rando phantom are placed on each eight sites in seperately H&N, thoracic, abdominal section. each 4 methods of scan modes of are measured the for skin dose in three time. Subsequently, obtained average value. Following image quality QA protocol of equipment manufacturers using the catphan 504 phantom, image quality of each scan mode is compared and analyzed. Results: The results of the measured skin dose are described in here. The skin dose of Head & Neck are measured mode A: 8.96 cGy, mode B: 4.59 cGy, mode C: 3.46 cGy mode D: 1.76 cGy and thoracic mode A: 9.42 cGy, mode B: 4.58 cGy, mode C: 3.65 cGy, mode D: 1.85 cGy, and abdominal mode A: 9.97 cGy, mode B: 5.12 cGy, mode C: 4.03 cGy, mode D: 2.21 cGy. Approximately, dose of mode B are reduced 50%, mode C are reduced 60%, mode D are reduced 80% a point of reference dose of mode A. the results of analyzed HU reproducibility, low contrast resolution, spatial resolution (high contrast resolution), HU uniformity in evaluation item of image quality are within the tolerance value by recommended equipment manufacturer in all scan mode. Conclusion: Maintaining the image quality as well as reducing the image dose are very important in cone beam CT. In the result of this study, we are considered when to take mode A when interested in soft tissue. And we are considered to take mode D when interested in bone scan and we are considered to take mode B, C when standard scan. Increasing secondary cancer risk due to cone beam CT scan should be reduced by low mAs technique.

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Utility Evaluation of Split VMAT Treatment Planning for Nasopharyngeal cancer (비인두암 Split VMAT 치료계획 유용성 평가)

  • Tae Yang Park;Jin Man Kim;Dong Yeol Kwon;Jun Taek Lim;Jong Sik Kim
    • The Journal of Korean Society for Radiation Therapy
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    • v.34
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    • pp.13-20
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    • 2022
  • Purpose : IMRT using Tomotherapy during nasopharyngeal cancer radiation therapy irradiate an accurate dose to tumor tissues and is effective to reduce a dose rapidly in normal tissues. However, this has high MU and long Beam On Time. This study aims to analyze differences in tumors, normal tissues and low-dose distributions and the efficiency of Split VMAT after applying Helical IMRT (Tomotherapy), VMAT (Linac : 2Arc) and Split VMAT (Linac : 4Arc) plans. Materials and Methods : This study targeted ten nasopharyngeal cancer patients of this hospital and compared three treatment plans (Helical IMRT, VMAT, Split VMAT). For Helical IMRT planning, Precision® (Version 1.1.1.1, Accuray, USA) was used, and for VMAT and Split VMAT planning, Pinnacle (Version 9.10, Philips, USA) was used. The total dose applied was 38.4 Gy / 32 Gy (Daily Dose 2.4 Gy (GTV + 0.3 cm) / 2 Gy (CTV + 0.3 cm) 16Fx), and for GTV + 0.3 cm (P_GTV), 95% of V38.4Gy was prescribed. VMAT with an angle of 360° 2Arc was applied, and for Split VMAT, the field was divided into the right, the left, the top and the bottom and an angle of 360° 4Arc, 6MV was set. For evaluating the quality of the treatment plans, differences in tumors, normal tissues and low-dose area were compared, and Beam On Time was measured to analyze the efficiency. Results : When calculating the mean values of evaluation items of the three treatment plans (Helical IMRT, VMAT, Split VMAT) for the patients, the H.I (Homogeneity Index) of P_GTV was 1.04, 1.11 and 1.1 respectively, and the C.I (Confomity Index) of P_CTV was 1.03, 0.99 and 1.00 respectively. The mean dose of RT Parotid Gland (Gy) was 14.54, 17.06 and 14.76 respectively, the mean dose of LT Parotid Gland (Gy) was 14.32, 17.32 and 15.09 respectively, the maximum dose of P_Cord (Spinal Cord + 0.3 cm) (Gy) was 20.57, 22.59 and 21.06 respectively, and the maximum dose of Brain Stem (Gy) was 22.35, 23.99 and 21.68 respectively. The 50% isodose curve (cc) was 1332, 1132.5 and 1065.2 respectively. Beam On Time (sec) was 373.7, 130.7 and 254.4 respectively. Conclusion : Displaying a similar treatment plan quality to Helical IMRT, which is used a lot for head and neck treatment, Split VMAT reduced the low-dose area and Beam On Time and produced a better result than VMAT. Therefore, it is considered that Split VMAT is effective not only for nasopharyngeal cancer but also for other head and neck cancers.