• Title/Summary/Keyword: repeated dose

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The Toxicological Pathologic Study of Amanita muscaria in Sprague-Dawley Rat (Amanita muscaria 경구투여 시 Sprague-Dawley Rat에서의 독성병리 연구)

  • Kim, Jin;Kim, Hyeong-Jin;Kim, So-Jung;Kim, Byeong-Soo;Kim, Sang-Ki;Park, Byung-Kwon;Park, Young-Seok;Cho, Sung-Dae;Jung, Ji-Won;Nam, Jeong-Seok;Choi, Chang-Sun;Lee, Seung-Ho;Jung, Ji-Youn
    • Journal of Life Science
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    • v.19 no.8
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    • pp.1152-1158
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    • 2009
  • For the toxicological pathologic study of amanita muscaria, we have investigated single and repeated dose toxicity in Sprague-Dawley (SD) rats. Single dose toxicity study was identified as catalepsy, incline and tail pinch methods (control 0 mg/kg, low 3.3 mg/kg, middle 16.5 mg/kg, high 33.0 mg/kg). Repeated dose toxicity study was carried out in blood tests, serum tests and histopathological methods. Neurotoxicity - muscle paralysis, and convulsion and loss of movement - was observed at 33.0 mg/kg group in the single dose toxicity study. Dysfunction of liver and kidney were shown in the repeated oral administration of the amanita muscaria at 3${\sim}$4 weeks. Serum chemistry results revealed a marked increase of LDH [Lactate Dehydrogenase (3181.5 IU/L; normal 230-460 IU/l)], ALT [Alanine transaminase (124.0 IU/l; normal <40 IU/l)] but the kidney was normal. Histopathological results show interstitial edema and tubular epithelial necrosis in the kidney. These results suggest that amanita muscaria has a neurotoxic effect and causes dysfunction of liver and kidney in the SD rat.

Evaluation of Usefulness on In-vivo Diode Dosimetry for Measuring the Tumor Dose of Oral Cancer Patient (구강암 환자의 종양 선량 측정을 위한 In-vivo Diode Dosimetry의 유용성 평가)

  • Na Kyung-Su;Lee Je-Hee;Park Heung-Deuk
    • The Journal of Korean Society for Radiation Therapy
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    • v.17 no.2
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    • pp.133-140
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    • 2005
  • Purpose : This test is designed to identify the validity of treatment plan by implementing real-time dosimetry by means of dose that is absorbed into PTV and OAR when preparing doses of 3D and POP plans. Materials and Methods : In treatment. error can be calculated be comparing Exp. Dose with the actual dose, which has been converted from 'the reading value obtained by placing diode detector on the area to be measured'. Same test can be repeated using Alderson-Rando phantom. Results : Errors were found: A patient(POP plan): 197.6/199=-1.2%, B patient(3D-plan): 199.9/198.7=+0.6%, C patient: 196/200=-1.5%. In addition, considering the resulted value of measuring OAR besides target-dose for C patient showed 96/200, representing does of 47%, the purpose of protection was judged to be duly accomplished. Also it was acknowledged the resulted value of -3.7% met the targeted dose within the range of ${\pm}5%$. Conclusion : Aimed for identifying the usefulness of pre-treatment dose measurement using diode detector, this test was useful to evaluate the validity of curing because it resulted in the identification of category to be protected as well as t dose. Moreover, it is thought to have great advantage in ascertaining the dose of target, dose of which is not calculated yet. Similar to L-gram before treatment, this test is thought to be very effective so that it can bring great advantages in the aspects such as validity of curing method and post-treatment plan as well.

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Study on the Toxicity of Jihwangbakhotang in Rats (지황백호탕(地黃白虎楊)의 독성효과(毒性效果)에 관(關)한 연구(硏究))

  • Na, Dal-Rye;Kim, Kyung-Yo;Lee, Jong-Duck
    • Journal of Sasang Constitutional Medicine
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    • v.9 no.2
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    • pp.203-225
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    • 1997
  • Jihwangbakhotang(地黃白虎楊) is made by Li Je Ma, the creator of the Four Constitutional Medicine. Single and 13 weeks oral repeated dose toxicity studies were conducted in Sprague Dawley rats of both sexes to elucidate the potential acute and subchronic toxicity of JBT extract and reversibility of any effects. In the single dose study, JBT extract was administered orally to rats with the dose of 2 g/kg and 8 g/kg. In the long term administration of 13 weeks, the JBT extract of 125 mg/kg/day, 500 mg/kg/day, 2000 mg/kg/day was administered to rats. The change of blood weight, urine volume, electrolyte in urine, hematological change, the change of blood chemistry, autopsy finding, and histological observation were researched, the results were as follows; 1. The lethal dose of JBT extract seems to be over 10 g/kg, the single administration of JBT extract 8 g/kg showed no toxical signs except little increase of urine volume. 2. The change of body weight had the trend of decrease in the group of, but has no significance, and also the consumption of food and water had no changes. 3. The hematological changes induced by the 13 weeks administration of JBT extract showed the significance in the item of Hb, MCH, MCV, WBC in the group of 125 mg/kg/day. 4. In the test of blood chemistry, total cholesterol showed little decrease and A/G ratio showed little increase, but the change was not clear, and the standard error was large. So the result was obtained insignificantly and the toxicity of JBT extract was not observed. 5. In the male group after recovery period, the level of cholesterol and triglyceride decreased slightly, but the result was not significant. 6. In the urine test, the little change of electrolyte was appeared, but it seemed not to be the result induced by the toxicity of JBT extract. 7. In each group of male and female rats, the weight change of organ and the serum histological changes was observed, but the result did not showed the dose dependent toxicity. So the toxicity of JBT extract was not regarded. In the conclusion, the toxicity of JBT extract was not observed in the single dose treatment and long term repetitive administration of JBT extract.

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Single Dose Toxicity Test of Mahwangyounpae-tang Extract in Male SD Rats (마황윤폐탕(麻黃潤肺湯) 추출물의 수컷 SD Rats에서 경구 단회투여 독성 평가)

  • Cho, Dong-Hee;Park, Mee-Yeon;Choi, Hae-Yun;Kim, Jong-Dae;Jeon, Kwi-Ok
    • The Journal of Internal Korean Medicine
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    • v.27 no.1
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    • pp.102-113
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    • 2006
  • Objectives & Methods : To obtain the 50% lethal dose(LD50), approximated lethal dose(ALD) and approximated target organs of 'Mahwangyounpae-tang' for further study into such things as repeated dose toxicity, genotoxicity and reproductive toxicity, single dose toxicity was tested in male SD rats according to KFDA Guideline 1999-61[KFDA, 1999] at dosage levels of 2,000, 1,000, 500, 250 and 125 mg/kg/$10m{\ell}$. In this study, mortalities, clinical signs, body weight changes and body weight gains, gross findings and weight of principal organs were detected during and/or after 14 days of single dosing. Results & Conclusions : After 2 or 3 days of dosing, 1 or 2 animals in 2,000 mg/kg-dosing groups died. Excitation and leaping response were observed as test article-treatment related clinical signs. These abnormal signs were restricted to 2,000 and 1,000 mg/kg-dosing groups and survivors recovered to normal within 3 or 4 days after dosing. Significant decrease in body weight were observed in some periods of observation in 2,000 and 1,000 mg/kg-dosing group, from 1 days after dosing compared to those of vehicle control group. Significantly diminished body weight gains were observed in observation periods in 2,000 and 1,000 mg/kg-dosing group compared to those of vehicle control group. Hypertrophy and hemorrhage of heart and decoloration of kidney were observed as test article-treatment related gross findings. These abnormal findings were restricted to 2,000 and 1,000 mg/kg-dosing groups. A significant increase of absolute and relative heart and kidney weight were demonstrated in 2,000 mg/kg-dosing groups. The value for LD50 found in this study was 2,218.57 mg/kg. ALD in this study was 2,000 mg/kg, and the target organs are considered to be the heart and the kidney.

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Low-Dose Bisphenol A Increases Bile Duct Proliferation in Juvenile Rats: A Possible Evidence for Risk of Liver Cancer in the Exposed Population?

  • Jeong, Ji Seong;Nam, Ki Taek;Lee, Buhyun;Pamungkas, Aryo Dimas;Song, Daeun;Kim, Minjeong;Yu, Wook-Joon;Lee, Jinsoo;Jee, Sunha;Park, Youngja H.;Lim, Kyung-Min
    • Biomolecules & Therapeutics
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    • v.25 no.5
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    • pp.545-552
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    • 2017
  • Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females. Notably, proliferative changes with altered cell foci and focal inflammation were observed around bile ducts in the liver of all BPA-dosed groups in males, which achieved statistical significance from 0.5 mg/kg (ANOVA, Dunnett's test, p<0.05). Toxicokinetic analysis revealed that systemic exposure to BPA was greater at early age (e.g., 210-fold in $C_{max}$, and 26-fold in AUC at 50 mg/kg in male on day 1 over day 90) and in females (e.g., 4-fold in $C_{max}$ and 1.6-fold in AUC at 50 mg/kg vs. male on day 1), which might have stemmed from either age- or gender-dependent differences in metabolic capacity. These results may serve as evidence for the association between risk of cancer and exposure to low-dose BPA, especially in young children, as well as for varying toxicity of xenobiotics in different age and gender groups.

Subacute Inhalation Toxicity Study of Dimethyl Disulfide in F344 Rats (F344 랫드를 이용한 이황화메틸의 아급성 흡입독성연구)

  • Kim Hyeon-Yeong;Lee Sung-Bae;Han Jung-Hee;Chung Yong-Hyun;Kim Hyoung-Chin;Shin Jin-Young;Shin Dong-Ho;Kim Jong-Choon;Lee Young-Mook
    • Journal of Life Science
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    • v.15 no.1 s.68
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    • pp.1-8
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    • 2005
  • The purpose of this study was to investigate the potential subacute toxicity of dimethyl disulfide by 3 weeks inhalation in F344 rats. The test article, dimethyl disulfide was exposed by inhalation to male and female rats at dose levels of 0, 5, 25, or 125 ppm/6 hrs/ day for 3 weeks. Five rats/ sex/ group were sacrificed on day 4 after the initiation of treatment, while 5 rats/ sex/ group were sacrificed at the end of treatment period. During the test period, clinical signs, mortality, body weights, food consumption, hematology, serum biochemistry, and gross findings were examined. Slight decreases in body weight gain were noted in both sexes of the highest dose group in a dose dependent manner but were only statistically different from the control animals in males of the group. A slight non-significant reduction in food consumption were also noted in the both sexes of the highest dose group. There were no adverse effects on mortality, clinical signs, hematology, serum biochemistry, and necropsy findings at any dose tested. Based on these results, it was concluded that the 3 weeks repeated dose of dimethyl disulfide by inhalation resulted in suppressed body weight gain and decreased food consumption at 125 ppm of both sexes. In the present experimental conditions, the target organ was not determined in rats. The no­observed-adverse-effect level (NOAEL) was considered to be 25 ppm/6 hrs/day for both sexes.

Dose and Image Assessment according to Radiologic Factors Variation at Digital Humerus X-ray Examination (디지털 환경에서 Humerus 검사 시 촬영인자 변화에 따른 선량 및 화질 평가)

  • Kim, Seong Min;Hong, Seon Sook;Lee, Kwan Sup;Ha, Dong Yun
    • Korean Journal of Digital Imaging in Medicine
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    • v.14 no.2
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    • pp.1-8
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    • 2012
  • Purpose : We aim at presenting the optimum radiologic factor through the evaluation of dose variation and of image quality through the use of a grid in Humerus examination and the change of dose because of the change of radiologic factor. Materials and Methods : We divided it in 3 cases: when using a grid or not and when using IP(Image Plate) in a digital system. Also, as fixing kVp to 70kVp it changed mAs, and fixing mAs to 10 it changed kVp, we put up resolution chart and Burger rose phantom on the acrylic phantom of 7cm (the same level of Humerus) to evaluate the dose and image. We used Image J program to evaluate the quantitative resolution of the obtained image, and made the qualitative evaluation and statistical analysis of the image saved in PACS for 20 radiologic technologist with more than 10 years of experience in order of evaluate its contrast. We used SPSS10(SPSS Inc. Chicago, Illinois) for statistical analysis. Results : We observed the analytic result of resolution by the change of kVp that it was $4.539dGycm^2$ in 60kVp and $757.472dGycm^2$ in 75kVp, which increased about 64.6% of dose, while for the resolution it had the pixel value 30.7% better with 851 in 60kVp than 651 in 75kVp. Also, we analyzed the result of resolution by the change of mAs that it was $3.106dGycm^2$ in 5mAs, and $12.470dGycm^2$ in 20mAs, which increased about 400% of dose, while for the resolution DR had 678 in 5mAs, and 724 in 20mAs that increased about 6.8% of resolution. We made the qualitative evaluation of contrast by the change of kVp that DR showed the higher quality than CR, but the contrast by the change of kVp had no special different at the moment of visual evaluation, nor statistically significant difference(P>0.05). We observed the qualitative evaluation of contraste by the change of mAs that the contrast increased as DR increased mAs, and had statistically significant difference(P<0.05). On the other hand, CR had no significant difference for more than 10mAs nor statistically significant difference(P>0.05). Conclusion : In case of some patients with radiographic exposure by the repeated examination such as emergent patient or Follow up patient, they are considered to try to limit the use of a grid, to set kVp under 65kVp in fixed mode, to select less than 10mAs and to reduce the possibility of patient being bombed.

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Direct Measurement of Chamber Response Function and Its Application to Radiation Dose Distribution Dosimetry (전리함 반응 함수의 직접 측정과 이를 이용한 방사선의 실제선량 분포측정)

  • Lee Sang Hoon;Cho Byung Chul;Kim Jong Hoon;Choi Eun Kyung;Kwon Soo Il;Chang Hyesook;Yi Byong Yong
    • Radiation Oncology Journal
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    • v.15 no.1
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    • pp.65-69
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    • 1997
  • Purpose : To obtain the actual dose distribution from measured data by doconvolution method using the measured ion chamber response function. Materials and Methods : The chamber response functions for 2 ionization chambers (diameter 5mm, 6.4mm) were measured. and dose Profiles were measured for $10{\times}20cm^2$ field size using two different detectors. The deconvolution of chamber response function from the measured data were performed for these Profiles. The same procedures were repeated for 4MV, 6MV and 1 SMV photon energies. Results : Different dose Profiles were obtained for the same field with the chambers which have the different response functions. Nearly the same results could be obtained with deconvolution for the profiles from various detectors. Conclusion : The effect of the chamber response function can be extracted by deconvolution method. Deconvolved dose profile using various ionization chambers gave better dose distributions. Technical improvements are needed for practical application.

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Identification of an effective and safe bolus dose and lockout time for patient-controlled sedation (PCS) using dexmedetomidine in dental treatments: a randomized clinical trial

  • Seung-Hyun Rhee;Young-Seok Kweon;Dong-Ok Won;Seong-Whan Lee;Kwang-Suk Seo
    • Journal of Dental Anesthesia and Pain Medicine
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    • v.24 no.1
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    • pp.19-35
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    • 2024
  • Background: This study investigated a safe and effective bolus dose and lockout time for patient-controlled sedation (PCS) with dexmedetomidine for dental treatments. The depth of sedation, vital signs, and patient satisfaction were investigated to demonstrate safety. Methods: Thirty patients requiring dental scaling were enrolled and randomly divided into three groups based on bolus doses and lockout times: group 1 (low dose group, bolus dose 0.05 ㎍/kg, 1-minute lockout time), group 2 (middle dose group, 0.1 ㎍/kg, 1-minute), and group 3 (high dose group, 0.2 ㎍/kg, 3-minute) (n = 10 each). ECG, pulse, oxygen saturation, blood pressure, end-tidal CO2, respiratory rate, and bispectral index scores (BIS) were measured and recorded. The study was conducted in two stages: the first involved sedation without dental treatment and the second included sedation with dental scaling. Patients were instructed to press the drug demand button every 10 s, and the process of falling asleep and waking up was repeated 1-5 times. In the second stage, during dental scaling, patients were instructed to press the drug demand button. Loss of responsiveness (LOR) was defined as failure to respond to auditory stimuli six times, determining sleep onset. Patient and dentist satisfaction were assessed before and after experimentation. Results: Thirty patients (22 males) participated in the study. Scaling was performed in 29 patients after excluding one who experienced dizziness during the first stage. The average number of drug administrations until first LOR was significantly lower in group 3 (2.8 times) than groups 1 and 2 (8.0 and 6.5 times, respectively). The time taken to reach the LOR showed no difference between groups. During the second stage, the average time required to reach the LOR during scaling was 583.4 seconds. The effect site concentrations (Ce) was significantly lower in group 1 than groups 2 and 3. In the participant survey on PCS, 8/10 in group 3 reported partial memory loss, whereas 17/20 in groups 1 and 2 recalled the procedure fully or partially. Conclusion: PCS with dexmedetomidine can provide a rapid onset of sedation, safe vital sign management, and minimal side effects, thus facilitating smooth dental sedation.

Effect of Diazinon, an Organophosphate Insecticide, on Plasma Lipid Constituents in Experimental Animals

  • Ibrahim, Nagi A.;El-Gamal, Basiouny A.
    • BMB Reports
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    • v.36 no.5
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    • pp.499-504
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    • 2003
  • There has been increasing interest in studying the various effects of organophosphate insecticides in humans and experimental animals. Only a few data are available on the effect of the organophosphate insecticide, diazinon, on lipid metabolism. The aim of this study was to evaluate the effect of diazinon on plasma lipid constituents in mammalian animals. The plasma levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and phospholipids (PL) were measured in albino rats that were orally treated with a single dose of diazinon at a level of $LD_{50}$ or with repeated daily doses at the levels of $\frac{1}{2}$, $\frac{1}{8}$, and $\frac{1}{32}$ $LD_{50}$ for 2, 8, and 32 days, respectively. After a 24 h post-treatment with a single $LD_{50}$ dose of diazinon, TC was not significantly changed, the HDL-C and PL levels were significantly decreased, but the LDL-C and TG levels were significantly increased. Separate daily oral administrations of diazinon at $\frac{1}{2}$ $LD_{50}$, $\frac{1}{8}$ $LD_{50}$, and $\frac{1}{32}$ $LD_{50}$ doses resulted in a significant decrease in HDL-C and PL, with no significant change in TG. The LDL-C levels were significantly increased and TC showed no significant change with $\frac{1}{2}$ $LD_{50}$ and $\frac{1}{32}$$LD_{50}$ doses of diazinon, whereas a significant decrease in the levels of TC, HDL-C, as well as LDL-C, was observed with the $\frac{1}{8}$ $LD_{50}$ dose. These data suggest that diazinon may interfere with lipid metabolism in mammals.