• 제목/요약/키워드: repeated dose

검색결과 494건 처리시간 0.026초

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

  • 최형준;임수정;박해리;이성미;김철응;류승형
    • 생물정신의학
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    • 제27권1호
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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
    • 대한약침학회지
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    • 제18권2호
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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
    • 한국임상수의학회지
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    • 제38권1호
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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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    • 제39권4호
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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.

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

  • 김현주
    • 한국방사선학회논문지
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    • 제17권6호
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    • pp.819-825
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    • 2023
  • 흉부 CT 검사 조건 중 관전압을 100, 80 kVp, 재구성 알고리즘을 FBP, ASIR-V, DLIR로 변화 적용하여 검사 선량과 화질 변화를 비교 분석해 보았다. 그 결과 기존 관전압 보다 낮은 관전압인 100 kVp 에서 ASIR-V, DLIR 적용 시 선량을 낮추면서 120 kVp, FBP 적용 시와 가장 유사한 화질로 구현. 특히, DLIR 재구성 영상은 모든 관전압에서 SNR, CNR이 우수하였다. 또한, SSIM 지수가 1에 가장 근사하게 분석되어 원본 영상과 가장 유사도가 높은 것을 알 수 있었다. 따라서 반복적으로 흉부 CT 검사를 시행하는 경우 DLIR 적용은 검사 선량을 약 29.7% 감소시킬 수 있어 CT 검사의 가장 큰 문제점인 검사로 인한 피폭을 일부 해결하는 데 도움을 줄 수 있을 것으로 사료된다.

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

  • 한수철;김금배;최상현;박승우;정해조;지영훈
    • 한국의학물리학회지:의학물리
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    • 제27권2호
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    • pp.98-104
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    • 2016
  • 본 연구는 고선량으로 인한 광자극발광선량계의 방사선 민감도 변화에 관하여 분석하기 위하여 60-Co 감마선에서 상용화된 광자극발광선량계(Landauer, Inc., Glenwood, IL)를 이용하였다. 고선량으로 인한 방사선 민감도 변화를 분석하기 위하여 한번도 사용하지 않은 소자들을 이용하여 상대적 방사선 민감도 변화 경향을 확인하였으며, 7번째까지 3% 정도 증가하다가 그 이후 1 Gy의 조사 횟수에 따라 0.35%씩 감소하는 것을 확인하였다. 그리고 30회까지 조사하였을 때 7% 감소하였다. 고 선량을 받은 소자들의 경우, 15 Gy가 조사된 그룹은 한번도 사용하지 않은 소자들의 방사선 민감도에 비해 6% 감소하였으며, 30 Gy가 조사된 그룹은 12% 감소하였다. 감소되는 경향은 지수함수에 곡선 맞춤 하였다. 고선량을 받은 소자들을 다시 재 사용할 경우 측정에 대한 큰 불확도를 가지고 있으며, 이를 인지 하고 소자에 대한 조사 이력 관리를 하면서 사용해야 할 것이다.

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

  • 김형욱;강경선;신동진;조재진;김배환;서광원;남기환;이영순
    • Toxicological Research
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    • 제8권2호
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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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복부 일반촬영시 초점-필름간거리 변화가 피폭선량 및 화질에 미치는 영향 (Effects on Patient Exposure Dose and Image Quality by Increasing Focal Film Distance in Abdominal Radiography)

  • 김유현;권수일
    • 대한방사선기술학회지:방사선기술과학
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    • 제21권1호
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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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김치에서 분리한 Leuconostoc Citreum GR1의 흰쥐에 대한 반복투여독성 (Four-Week Repeated Oral Toxicity Study of Leuconostoc citreum GR1 in Rats)

  • 김아라;이명렬;장해춘;이재준
    • 한국식품영양과학회지
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    • 제42권4호
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    • pp.600-607
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    • 2013
  • 본 연구는 김치 유래 유산균인 Leuc. citreum GR1의 안정성을 평가하고자 Leuc. citreum GR1을 SD 계통의 흰쥐에게 4주간 반복 경구투여를 통하여 장기투여에 의한 안전성을 확인하고자 식품의약품안전청의 의약품 등의 독성시험기준에 따라 실시하였다. SD 계열의 암수 흰쥐에 시험물질을 0, 500, 1,000 및 2,000 mg/kg/day의 용량으로 4주간 반복 경구투여 한 후 사망률, 일반증상, 체중변화, 사료섭취량, 수분섭취량, 부검소견, 장기무게의 변화, 혈액학적, 혈액생화학적 및 병리조직학적 검사를 실시하였다. 모든 시험군에서 시험기간 시험물질로 인한 일반증상 및 사망동물이 관찰되지 않았다. 전 시험기간 동안 Leuc. citreum GR1의 4주간의 경구투여 결과 체중이 지속적으로 증가되었지만 대조군과 유의성 있는 변화가 관찰되지 않았다. 또한 장기의 육안적 관찰, 장기 중량변화, 혈액학적, 혈액생화학적 및 병리조직학적 검사에서도 모든 시험물질 투여군이 대조군과 유의성이 있는 차이를 보이지 않았으며, 모두 정상 범위를 벗어나지 않아 시험물질에 기인하는 이상 소견을 발견할 수 없었다. 이상의 결과로 보아 4주 반복투여 독성시험 결과 김치 유산균인 Leuc. citreum GR1은 저독성의 안전한 물질로 판정되며, 본 시험물질의 무독성량은 암수 모두 2,000 mg/kg/day 이상을 상회하는 것으로 판단되었다.

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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    • 제26권4호
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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.