• Title/Summary/Keyword: repeated dose

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Ketamine-Induced Behavioral Effects Across Different Sub-Anesthetic Dose Ranges in Adolescent and Adult Mice (다양한 마취하 용량에서 케타민에 의해 유발된 청소년기 및 성체 마우스의 행동학적 변화)

  • Choi, Hyung Jun;Im, Soo Jung;Park, Hae Ri;Lee, Seong Mi;Kim, Chul-Eung;Ryu, Seunghyong
    • Korean Journal of Biological Psychiatry
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    • v.27 no.1
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    • pp.27-35
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    • 2020
  • Objectives Ketamine has been reported to have antidepressant effects or psychotomimetic effects. The aim of this study was to investigate the behavioral effects of ketamine treatment at various sub-anesthetic doses in adolescent and adult naïve mice. Methods In each experiment for adolescent and adult mice, a total of 60 male Institute of Cancer Research mice were randomly divided into 6 groups, which were intraperitoneally treated with physiological saline, 10, 20, 30, 40, and 50 mg/kg ketamine for consecutive 3 days. At 1 day after last injection, the locomotor and depressive-like behaviors were evaluated in mice, using open field test (OFT) and forced swim test (FST), respectively. Results In case of adolescent mice, ketamine dose was negatively correlated with total distance traveled in the OFT (Spearman's rho = -0.27, p = 0.039). In case of adult mice, we found significant positive correlation between ketamine dose and duration of immobility in the FST (Spearman's rho = 0.45, p < 0.001). Immobility time in the 50 mg/kg ketamine-treated mice was significantly higher compared to the saline-treated mice (Dunnett's post-hoc test, p = 0.012). Conclusions We found that the repeated treatment with ketamine could decrease the locomotor or prolong the duration of immobility in mice as the dose of ketamine increased. Our findings suggest that sub-anesthetic doses of ketamine might induce schizophrenia-like negative symptoms but not antidepressant effects in naïve laboratory animals.

Single-dose Toxicity of Water-soluble Ginseng Pharmacopuncture Injected Intramuscularly in Rats

  • Yu, Junsang;Sun, Seungho;Lee, Kwangho;Kwon, Kirok
    • Journal of Pharmacopuncture
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    • v.18 no.2
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    • pp.76-85
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    • 2015
  • Objectives: Radix Ginseng has been traditionally used as an adaptogen that acts on the adrenal cortex and stimulates or relaxes the nervous system to restore emotional and physical balance and to improve well-being in cases of degenerative disease and/or old age. Radix Ginseng has been used for a long time, but the safety of ginseng pharmacopuncture needs testing. This study was done to analyze the single-dose toxicity of water- soluble ginseng pharmacopuncture (GP) intramuscular injections in rats. Methods: All experiments were performed at Biotoxtech, an institution authorized to perform non clinical studies under the regulations of Good Laboratory Practice (GLP). Each group contained 10 Sprague-Dawley rats, 5 males and 5 females. GP was prepared in a sterile room at the Korean Pharmacopuncture Institute under regulations of Good Manufacturing Practice (GMP). GP dosages were 0.1, 0.5 and 1.0 mL for the experimental groups; normal saline was administered to the control group. The animals general condition was examined daily for 14 days, and the rats were weighed on the starting day and at 3, 7 and 14 days after administration of the pharmacopuncture. Hematological and biochemistry tests and autopsies were done to test the toxicological effect of GP after 14 days. This study was performed with approval from the Institutional Animal Ethics Committee of Biotextech. Results: No deaths were found in this single-dose toxicity test of intramuscular injections of GP, and no significant changes in the general conditions, body weights, hematological and biochemistry tests, and autopsies were observed. The local injection site showed no changes. Based on these results, the lethal dose was assumed to be over 1.0 mL/animal in both sexes. Conclusion: These results suggest that GP is relatively safe. Further studies, including a repeated toxicity test, are needed to provide more concrete evidence for the safety of GP.

Safety Evaluation of Kyungokgo-gamibang Administration Based on Hematological, Biochemical, Protein, and Lipid Profiles in Dogs

  • Song, Doo-won;Lee, Ga-won;Ro, Woong-bin;Kim, Heyong-seok;Kang, Hyun-min;Kim, Jong-won;Park, Soo-bin;Moon, Yang-seon;Na, Chang-su;Park, Hee-myung
    • Journal of Veterinary Clinics
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    • v.38 no.1
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    • pp.7-15
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    • 2021
  • Kyungokgo-gamibang, Kyungokgo with Iksuyongjingo and Sparassis crispa, is a traditional Korean medicine used for restorative effects. This study aimed to evaluate the safety of Kyungokgo-gamibang in healthy beagle dogs. In the single-dose oral toxicity study, three beagle dogs were orally administered 2,000, 1,000, and 500 mg/kg of Kyungokgo-gamibang and were observed for 14 days. In the repeated-dose oral toxicity study, nine healthy dogs were orally administered 0.2g/kg of Kyungokgo-gamibang (n = 3, low-dose group), 1 g/kg of Kyungokgo-gamibang (n = 3, high-dose group), or normal saline (n = 3, control group) twice a day for 8 weeks. The hematological, serum biochemical, urine, protein, and lipid profiles were evaluated to investigate the adverse effects of the Kyungokgo-gamibang. During the study period, the dogs demonstrated no clinical signs and the hematological, serum biochemical, urine, protein, and lipid analyses revealed unremarkable findings. The study results suggest that Kyungokgo-gamibang can be safely administered to dogs without any adverse effects.

The Evaluation of the Acute Toxicity and Safety of Verbenalin in ICR Mice

  • Hyejeong, Shin;Yigun, Lim;Jisu, Ha;Gabsik, Yang;Taehan, Yook
    • Journal of Acupuncture Research
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    • v.39 no.4
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    • pp.310-316
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    • 2022
  • Background: Verbenalin is an iridoid glucoside, which is among the active components of some medicinal herbs such as Verbena officinalis Linn, and Cornus officinalis Siebold and Zucc. Previous studies have confirmed the antioxidant activity and neuroprotective potential of verbenalin. To confirm the safety of verbenalin, an approximate lethal dose was determined based on a single oral dose toxicity study. Methods: Institute of Cancer Research mice were randomly assigned to three verbenalin exposure groups (250, 500, and 1,000 mg/kg) and a control group (5% methylcellulose solution). There were (5 male and 5 female mice per group). Mortality, clinical signs, and body weight were monitored for 14 days, and necropsies were conducted. Results: No mortalities were observed in the control group or the verbenalin 250 mg/kg group, whereas mortalities were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups. During the observation period, stool abnormalities such as mucous stools were observed. Clinical signs such as loss of locomotor activity were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups. During the study period, significant changes in body weight were observed in the 500 mg/kg and 1,000 mg/kg verbenalin groups; however, no gross abnormalities were observed at necropsy. Overall, no toxicity was found in the 250 mg/kg group. Conclusion: The approximate lethal dose of verbenalin was estimated to be 500 mg/kg. For a more accurate assessment of the safety of verbenalin, other types of studies such as repeated-dose toxicity studies should also be conducted.

Analysis of Image Quality and Scan Dose when Applying Reconstruction Algorithm Changes to Chest CT Scans (흉부 CT 스캔에서 재구성 알고리즘 변화적용 시 화질과 스캔 선량 분석)

  • Hyeon-Ju Kim
    • Journal of the Korean Society of Radiology
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    • v.17 no.6
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    • pp.819-825
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    • 2023
  • In this study, among chest CT examination conditions, the tube voltage was changed to 100 and 80 kVp and the reconstruction algorithm was changed to FBP, ASIR-V, and DLIR to compare and analyze changes in examination dose and image quality. As a result, when applying ASIR-V and DLIR at a tube voltage of 100 kVp, which is lower than the existing tube voltage, the dose is lowered while achieving image quality most similar to that when applying 120 kVp and FBP. especially, DLIR reconstructed images had excellent SNR and CNR at all tube voltages. In addition, the SSIM index was analyzed to be closest to 1, showing the highest similarity to the original image. Therefore, when performing repeated chest CT examinations, the application of DLIR can reduce the examination dose by about 29.7%, which is expected to help solve some of the biggest problems with CT examinations, namely radiation exposure due to the examination.

Changes of Optically Stimulated Luminescence Dosimeter Sensitivity with High Dose (고선량에 대한 광자극발광선량계의 방사선 민감도 변화 연구)

  • Han, Su Chul;Kim, Kum Bae;Choi, Sang Hyoun;Park, Seungwoo;Jung, Haijo;Ji, Young Hoon
    • Progress in Medical Physics
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    • v.27 no.2
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    • pp.98-104
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    • 2016
  • We investigated the effect of high dose on the sensitivity of optically stimulated luminance dosimeters (OSLDs) on Co-60 gamma rays and used a commercial OLSD (Landauer, Inc., Glenwood, IL). New OSLDs were chosen arbitrarily and were irradiated with 1 Gy repeatedly. We confirmed the change in the radiation sensitivity after repeated irradiation. The OSLD sensitivity increased up to 3% after irradiating for seven times and decreased continuously after the eighth time. It dropped by approximately 0.35 Gy per irradiation. Finally, after irradiating for 30 times, the OSLD sensitivity decreased by approximately 7%. When the OSLDs were irradiated 10 times with 1 Gy after their irradiation using a high dose of 15 Gy and 30 Gy, their sensitivity decreased by 6% and 12%, respectively, compared to that before high-dose irradiation. The change in the OSLD sensitivity with a high dose could be modeled by an exponential equation. We confirmed the radiation sensitivity variation caused by a high dose, and the irradiation history of dosimeters was considered to reuse OSLDs irradiated with a high dose.

Subacute Toxicity of cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R) in rats (랫드에서 cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II)(SKI 2053R)의 아급성독성시험에 관한 연구)

  • Kim, Hyoung-Ook;Kang, Kyung-Sun;Shin, Dong-Jin;Cho, Jae-Jin;Kim, Bae-Hwan;Seo, Kwang-Won;Nam, Ki-Hoan;Lee, Yong-Soon
    • Toxicological Research
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    • v.8 no.2
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    • pp.217-233
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    • 1992
  • This study was performed to determine the toxic effects of graded dose levels of SKI 2053R after repeated administration. Three groups of Sprague-Dawley rats(10M and 10F per group) were given a total of 25 i.v. injections of SKI 2053R (1.50,3.75,9.38mg/kg/day). In order to compare the toxic effects of SKI 2053R with those of cisplatin, one group of Sprague-Dawley rats (10M and 10F per group) were given a total of 25 i.v.injections of cisplatin (1.70mg/kg/day). The dosing schedule was divided into five courses of 5 consecutive days with 16-day dose-free intervals between each course. No drug-related toxicity occurred in low dose level group (1.50mg/kg/day) of SKI2053R. From the results of hematological examination, peripheral WBC counts, RBC counts and hemoglobin of high dose level group(9.38mg/kg/day)of SKI 2053R were significantly lower than those of no-treated group. Other toxicities including reduced final body weight, proteinuria and hematuria were observed in high dose level group of SKI 2053R. But, no change was detected in serum biochemical values of SKI 2053R treated groups. All of the rats in cisplatin treated group were died between 3 and 13 weeks, while rats treated with SKI2053R survived to the end except one rat of middle dose level group(3.75mg/kg/day). In histopathological examinations, rats that received cisplatin manifested severe tubular damage in kidney and hemosiderosis in spleen, but no critical pathological lesion was observed in rats of other groups. Considering the results of this study, it was concluded that non-toxic dose of SKI 2053R in this treatment schedule was estimated to be 3.75 mg/kg/day and the maximum tolerated dose was to be higher than 9.38mg/kg/day. The toxic profiles fo SKI 2053R were different from those of cisplatin, and its toxicity was considerably lower than that of cisplatin.

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Effects on Patient Exposure Dose and Image Quality by Increasing Focal Film Distance in Abdominal Radiography (복부 일반촬영시 초점-필름간거리 변화가 피폭선량 및 화질에 미치는 영향)

  • Kim, You-Hyun;Kwon, Soo-Il
    • Journal of radiological science and technology
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    • v.21 no.1
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    • pp.52-58
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    • 1998
  • We can and must improve the diagnostic images using available knowledge and technology. At the same time we must strive to reduce the patient's integral and entrance radiation dose. Reducing the integral dose to the patient during the radiologic procedure is a primary concern of the patient, especially the pediatric patient, the radiologist and the technologist. A 100cm focal film distance generally is used for most over-table radiography. The early x-ray tubes and screen film combinations required long exposures, which often resulted in motion artifacts. But nowaday, we have the generators and x-ray tubes that can deliver the energy necessary in a very short time and the receptors that can record the information just as rapidly. And, we performed this studies to evaluate the patient exposure dose and the image quality by increasing focal film distance in diagnostic radiography. There are many factors which affected to exposure factor, but we studied to verify of FFD increase, only. Effect of increasing the focal film distance to a 140 cm distance was tested as follows; 1. The focal film distances were set at 100, 120, and 140cm. 2. A 18cm acryl(tissue equivalent) phantom was placed on the table top. 3. An Capintec 192 electrometer with PM 05 ion chamber was placed at the entrance surface of the phantom, and exposure were made at each focal film distances. 4. The procedure was repeated in the same manner as above except the ion chamber was placed beneath the phantom at the film plane. 5. Exit exposure were normalize to 8mR for each portions of the experiment. Based on the success of the empirical measurements, a detailed mathematical analysis of the dose reduction was performed using the percent depth dose data. The results of this study can be summerized as followings ; 1) Increasing FFD from 100 cm to 140 cm, we would create a situation that would have a significant effect on the overall quality of radiograph and achive the 17.42% reduction of entrance dose and the 18.95% reduction of integral dose that the patient receives. 2) Thickness of Al step wedge for equal film density increased with the long distance. 3) Increasing FFD, Magnification of image was lowered. 4) Resolution of image also increased with the FFD. As the results described above, we strongly recommend using the long FFD to provide better information for our patients and profession in abdomen radiographic studies.

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Four-Week Repeated Oral Toxicity Study of Leuconostoc citreum GR1 in Rats (김치에서 분리한 Leuconostoc Citreum GR1의 흰쥐에 대한 반복투여독성)

  • Kim, Ah-Ra;Lee, Myung-Yul;Chang, Hae-Choon;Lee, Jae-Joon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.4
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    • pp.600-607
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    • 2013
  • This study was performed to investigate the repeated-dose toxicity of Leuconostoc citreum GR1 (Leuc. citreum GR1), a lactic acid bacterium isolated from kimchi, in male and female rats. Sprague-Dawley male and female rats were divided into four group (ten animals in each group) and Leuc. citreum GR1 was administered daily by gavage to rats at dosage levels of 0, 500, 1,000, or 2,000 mg/kg/day for four weeks. There were no bacterial-related deaths or abnormal clinical signs in either gender of rats during the observation period. Furthermore, no differences were found between the control and treatment groups in terms of body weight, food intake, and water consumption. Hematological parameters, serum biochemical analysis, and histopathological examination also showed insignificant dose-dependent alterations. There were also no alterations in organ weights upon administration of Leuc. citreum GR1 alone. These results suggest the oral application of Leuc. citreum GR1, up to a dosage level of 2,000 mg/kg, causes no adverse effects in both male and female rats.

Ovarian Follicular Dynamics, Ovarian Follicular Growth, Oocyte Yield, In vitro Embryo Production and Repeated Oocyte Pick Up in Thai Native Heifers Undergoing Superstimulation

  • Chasombat, J.;Nagai, T.;Parnpai, R.;Vongpralub, T.
    • Asian-Australasian Journal of Animal Sciences
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    • v.26 no.4
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    • pp.488-500
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    • 2013
  • The objective of this study was to compare the effectiveness of the protocols for superstimulation of follicular growth in Thai native heifers. Heifers (n = 20) were randomly divided into four groups of five heifers/group. Heifers were given a single dose by i.m. administration of 100 mg Follicle Stimulating Hormone dissolved in polyvinylpyrrolidone (FSHp) at 24 h. Ovum pick up (OPU) occurred at 72 h ($F_{24}O_{72}$ protocol; Group 1) or 96 h ($F_{24}O_{96}$ protocol; Group 2), and at 36 h and OPU at 72 h ($F_{36}O_{72}$ protocol; Group 3) or 96 h ($F_{36}O_{96}$ protocol; Group 4) after follicular ablation. The dynamics of ovarian follicular growth were monitored by twice-daily ultrasonographic examinations. Blood sample collections were performed every 12 h after initiation of treatment for assessment of FSH, E2 and P4 profiles. All heifers were subjected to eight repeated sequential sessions of OPU. The follicular deviation commenced $24{\pm}5.32$ h after follicular ablation in all groups. The circulatory FSH surged quickly from 24 to 36 h (>0.8 ng/ml) after follicular ablation and circulatory estrogen levels steadily increased from 36 h until OPU in all groups. At the end of the OPU sessions, the mean number of aspirated follicles/heifer/session in $F_{36}O_{72}$ protocol (Group 3) and $F_{36}O_{96}$ protocol (Group 4) were higher than in the two other groups (p<0.05). The number of cumulus-oocyte complexes (COCs), cleaved and day 8 blastocysts rates in the $F_{36}O_{72}$ protocol (Group 3) were higher than in the other groups (p<0.05). It can be concluded that a single dose i.m. administration of 100 mg FSHp at 36 h and OPU at 72 h after follicular ablation ($F_{36}O_{72}$ protocol; Group 3) was the most effective protocol for superstimulation of follicular growth for repeated OPU and subsequent in vitro embryo production in Thai native heifers.