• Title/Summary/Keyword: Preclinical research

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A 90-day repeated-dose oral toxicity study on Flos lonicerae extract in Fischer 344/N rats (금은화(Flos lonicerae) 추출물의 Fischer 344/N 랫드를 이용한 90일간 반복 경구투여 독성시험)

  • Han, Zhong-Ze;Zhang, Hu-Song;Kang, Sang-Chul;Gil, Ki-Hyun;Kong, Kwang-Han;Kim, Do-Hyung;Ahn, Tae-Hwan;Bae, Jin-Sook;Go, Hyeon-Kyu;Han, Myoung-Kyu;Kim, Hak-Soo;Heo, Hyun-Suk;Park, Eun-Mi;Song, Si-Whan;Kim, Kap-Ho;Park, Chan-Koo;Lee, Hyun-Kul
    • Korean Journal of Veterinary Research
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    • v.48 no.4
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    • pp.401-411
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    • 2008
  • This study was performed to evaluate repeated-dose oral toxicities of Flos lonicerae extract in Fischer 344/n rats. Flos lonicerae was administered orally to rats at dose levels of 0, 37, 111, 333, 1,000 and 2,000 mg/kg/day. Each group consisted of 10 rats of each gender. The Flos lonicerae extract was given once a day, 5 times a week, for 90 day repeatedly. This study was conducted in accordance with the Protocol of Korea National Toxicology Program and The Standards of Toxicity Study for Medicinal Products. In the present study, there were no toxicologically significant changes in mortality, clinical signs, body weight gains, ophthalmoscopy, urine analysis, hematology, serum biochemistry, necropsy findings, organ weights, histopathology, estrus cycle and sperm examination of all animals treated with Flos lonicerae extract. These results suggest that the oral no observed adverse-effect level of the test item, Flos lonicerae extract, in rats is higher than 2,000 mg/kg/day in both genders. The target organs were not established.

A 90-day repeated-dose oral toxicity study on Chelidonium majus extract in Fischer 344/N rats (백굴채(Chelidonium majus) 추출물의 Fischer 344/N 랫드를 이용한 90일간 반복 경구투여 독성시험)

  • Kim, Do-Hyung;Zhang, Hu-Song;Kim, Kwang-Ho;Kang, Sang-Chul;Kim, Hak-Soo;Gil, Ki-Hyun;Kong, Kwang-Han;Ahn, Tae-Hwan;Bae, Jin-Sook;Go, Hyeon-Kyu;Kim, Kap-Ho;Park, Chan-Koo;Lee, Hyun-Kul;Song, Si-Whan;Han, Zhong-Ze
    • Korean Journal of Veterinary Research
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    • v.49 no.1
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    • pp.23-34
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    • 2009
  • This study was performed to evaluate repeated-dose oral toxicities of Chelidonium majus extract in Fischer 344/N rats. Chelidonium majus extract was administered orally to rats at dose levels of 0, 25, 74, 222, 666 and 2,000 mg/kg/day. Each group consisted of 10 rats of each gender. The Chelidonium majus extract was given once a day, 5 times a week, for 90 day repeatedly. This study was conducted in accordance with the Protocol of Korea National Toxicology Program (issued by National Institute of Toxicological Research) and The Standards of Toxicity Study for Medicinal Products (issued by Korea Food and Drug Administration). In the present study, There were no toxicologically significant changes in mortality, clinical signs, body weight gains, ophthalmoscopy, urine analysis, hematology, serum biochemistry, necropsy findings, organ weights, histopathology, estrus cycle and sperm examination of all animals treated with Chelidonium majus extract. These results suggest that the oral no observed adverse-effect level of the test item, Chelidonium majus extract, in rats is higher than 2,000 mg/kg/day in both genders. The target organs were not established.

Reproductive Toxicity Study of CONP01, a New Antiarthritic Agent: Developmental Study in Rats (새로운 관절염 치료제 CONP01의 생식독성연구: 랫드 배 · 태자 발생시험)

  • Lee June-Suk;Hong Dong Ho;Kim Kwang-Ho;Zhang Hu-Song;Gil Gi Hyun;Han Myong Kyu;Yang Hyun Ju;Bae Jin-Sook;Kim Nam Du;Song Si Whan
    • Toxicological Research
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    • v.21 no.1
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    • pp.23-29
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    • 2005
  • A developmental study of CONP01, a new antiarthritic agent, was conducted in Sprague-Dawley rats. Dosage of CONP01 0, 111, 333, and 1000 mg/kg/day were administered to dams orally from day 6 to day 16 of gestation. Two-third of dams per group were subjected to caesarean section on day day 20 of pregnancy for examination of their fetuses, and the remaining one-third of dams per group were allowed to deliver naturally for postnatal examination of their offspring. There was no change in the dams body weights, food consumptions, specific clinical sings and gross findings. There was significant decrease only in the absolute and relative weights of right ovary in 111 mg/kg treatment group, when compared with the vehicle control, whereas other organ weights were not changed. Moreover, no increase in the frequencies of external, visceral and skeletal malformation of fetuses were observed in the treated groups. These results suggest that the oral NOAEL (no observed adverse effect level) of CONP01 may be over 1,000 mg/kg in dams and fetuses of rats.

Initial Dosimetry of a Prototype Ultra-High Dose Rate Electron-Beam Irradiator for FLASH RT Preclinical Studies

  • Hyun Kim;Heuijin Lim;Sang Koo Kang;Sang Jin Lee;Tae Woo Kang;Seung Wook Kim;Wung-Hoa Park;Manwoo Lee;Kyoung Won Jang;Dong Hyeok Jeong
    • Progress in Medical Physics
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    • v.34 no.3
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    • pp.33-39
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    • 2023
  • Purpose: FLASH radiotherapy (RT) using ultra-high dose rate (>40 Gy/s) radiation is being studied worldwide. However, experimental studies such as preclinical studies using small animals are difficult to perform due to the limited availability of irradiation devices and methods for generating a FLASH beam. In this paper, we report the initial dosimetry results of a prototype electron linear accelerator (LINAC)-based irradiation system to perform ultra-high dose rate (UHDR) preclinical experiments. Methods: The present study used the prototype electron LINAC developed by the Research Center of Dongnam Institute of Radiological and Medical Sciences (DIRAMS) in Korea. We investigated the beam current dependence of the depth dose to determine the optimal beam current for preclinical experiments. The dose rate in the UHDR region was measured by film dosimetry. Results: Depth dose measurements showed that the optimal beam current for preclinical experiments was approximately 33 mA, corresponding to a mean energy of 4.4 MeV. Additionally, the average dose rates of 80.4 Gy/s and 162.0 Gy/s at a source-to-phantom surface distance of 30 cm were obtained at pulse repetition frequencies of 100 Hz and 200 Hz, respectively. The dose per pulse and instantaneous dose rate were estimated to be approximately 0.80 Gy and 3.8×105 Gy/s, respectively. Conclusions: Film dosimetry verified the appropriate dose rates to perform FLASH RT preclinical studies using the developed electron-beam irradiator. However, further research on the development of innovative beam monitoring systems and stabilization of the accelerator beam is required.

Sex as an important biological variable in biomedical research

  • Lee, Suk Kyeong
    • BMB Reports
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    • v.51 no.4
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    • pp.167-173
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    • 2018
  • Experimental results obtained from research using only one sex are sometimes extrapolated to both sexes without thorough justification. However, this might cause enormous economic loss and unintended fatalities. Between years 1997 and 2000, the US Food and Drug Administration suspended ten prescription drugs producing severe adverse effects on the market. Eight of the ten drugs caused greater health risks in women. Serious male biases in basic, preclinical, and clinical research were the main reason for the problem. This mini-review will describe why and how funding organizations such as the European Commission, the Canadian Institutes of Health Research, and the US National Institutes of Health have tried to influence researchers to integrate sex/gender not only in clinical research, but also in basic and preclinical research. Editorial policies of prominent journals for sex-specific reporting will also be introduced, and some considerations in integrating sex as a biological variable will be pointed out. To produce precise and reproducible results applicable for both men and women, sex should be considered as an important biological variable from basic and preclinical research.

Body Weight Changes of Laboratory Animals during Transportation

  • Lee, Sung-Hak;Nam, Hyun-Sik;Kim, Jin-Sung;Cho, Hye-Jung;Jang, Yu-Mi;Lee, Eun-Jung;Choi, Eun-Sung;Jin, Dong-Il;Moon, Hong-Sik
    • Asian-Australasian Journal of Animal Sciences
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    • v.25 no.2
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    • pp.286-290
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    • 2012
  • The majority of laboratory animals were transported from commercial breeders to a research facility by ground transportation. During the transportation, many biological functions and systems can be affected by stress. In this experiment, the change of body weight during the transportation was measured and the recovery periods from the transportation stress established based on the body weight changes. Total 676 laboratory animals which were aged between 3 to 9 wk old were studied. The transportation time taken from container packing to unpacking the container was approximately 24 h. The temperature of animal container was constantly maintained by air-conditioning and heating equipment. Rats were found to be more sensitive than mice. The body weight of rats was significantly decreased 3.71% (p<0.05) compared to the body weight of mice which decreased 0.9% There was no significant difference between the strains in the same species. When the changes of body weights were compared between delivery days, C57BL/6 mice showed the most variable changes compared to other species and strains. Consequently, C57BL/6 was more sensitive to stress than the other strains and the transportation process needs to be standardized to reduce between day variability. To establish the recovery periods from transportation stress, the body weight changes were measured during the acclimation period. Although the body weight of animals decreased during transportation, animals recovered their weight loss after the next day.

Electron beam scattering device for FLASH preclinical studies with 6-MeV LINAC

  • Jeong, Dong Hyeok;Lee, Manwoo;Lim, Heuijin;Kang, Sang Koo;Lee, Sang Jin;Kim, Hee Chang;Lee, Kyohyun;Kim, Seung Heon;Lee, Dong Eun;Jang, Kyoung Won
    • Nuclear Engineering and Technology
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    • v.53 no.4
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    • pp.1289-1296
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    • 2021
  • In this study, an electron-scattering device was fabricated to practically use the ultra-high dose rate electron beams for the FLASH preclinical research in Dongnam Institute of Radiological and Medical Sciences. The Dongnam Institute of Radiological and Medical Sciences has been involved in the investigation of linear accelerators for preclinical research and has recently implemented FLASH electron beams. To determine the geometry of the scattering device for the FLASH preclinical research with a 6-MeV linear accelerator, the Monte Carlo N-particle transport code was exploited. By employing the fabricated scattering device, the off-axis and depth dose distributions were measured with radiochromic films. The generated mean energy of electron beams via the scattering device was 4.3 MeV, and the symmetry and flatness of the off-axis dose distribution were 0.11% and 2.33%, respectively. Finally, the doses per pulse were obtained as a function of the source to surface distance (SSD); the measured dose per pulse varied from 4.0 to 0.2 Gy/pulse at an SSD range of 20-90 cm. At an SSD of 30 cm with a 100-Hz repetition rate, the dose rate was 180 Gy/s, which is sufficient for the preclinical FLASH studies.

Veterinary management protocol for non-human primates: quarantine, anesthesia, and postoperative care for mastoidectomy at animal research institutions

  • Yoon Beom Lee;Woori Jo;Eui-Suk Jeong;Tae Ku Kang;Gwang-Hoon Lee
    • Korean Journal of Veterinary Research
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    • v.63 no.4
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    • pp.35.1-35.10
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    • 2023
  • Non-human primate (NHP) research faces challenges due to zoonosis risk and complex veterinary management yet lacks standardized guidelines for animal care. Therefore, we developed an advanced veterinary management protocol for NHP quarantine, anesthesia, and postoperative care. Three female 4 to 5-year-old cynomolgus monkeys were anesthetized and underwent various tests, including body weight, temperature, blood tests, urinalysis, microbiological monitoring, and physical and dental examinations. Ivermectin and medicated baths were administered to eradicate ectoparasites and endoparasites, and testing was repeated 30 days later. Following quarantine, we performed computed tomography and anesthesia maintenance for mastoidectomy. To relieve pain and maintain body weight, we administered tramadol intramuscularly 4 times/day for 3 days and meloxicam subcutaneously twice daily for 14 days. Feed replacements were provided. During the 33-day quarantine period, physical examinations revealed no abnormalities indicative of infectious diseases, and no specific clinical symptoms were observed. Through a preliminary test of anesthesia time, we selected ketamine 4 mg/kg + medetomidine 50 ㎍/kg for short experiments such as computed tomography, and ketamine 8 mg/kg + medetomidine 50 ㎍/kg for intubation. Ten days after mastoidectomy, NHPs consumed 100 kcal/kg and recovered their body weight. This study offers advanced veterinary management guideline for NHP research. Such protocols can lead to more standardized and ethical practices in NHP research, thereby enhancing the quality of studies on NHPs and the translation of findings to human health and disease.