• 제목/요약/키워드: Safe dose

검색결과 542건 처리시간 0.026초

Effects of dietary supplementation of high-dose folic acid on biomarkers of methylating reaction in vitamin $B_{12}$-deficient rats

  • Min, Hye-Sun
    • Nutrition Research and Practice
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    • 제3권2호
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    • pp.122-127
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    • 2009
  • Folate is generally considered as a safe water-soluble vitamin for supplementation. However, we do not have enough information to confirm the potential effects and safety of folate supplementation and the interaction with vitamin $B_{12}$ deficiency. It has been hypothesized that a greater methyl group supply could lead to compensation for vitamin $B_{12}$ deficiency. On this basis, the present study was conducted to examine the effects of high-dose folic acid (FA) supplementation on biomarkers involved in the methionine cycle in vitamin $B_{12}$-deficient rats. Sprague-Dawley rats were fed diets containing either 0 or $100{\mu}g$ (daily dietary requirement) vitamin $B_{12}/kg$ diet with either 2 mg (daily dietary requirement) or 100 mg FA/kg diet for six weeks. Vitamin $B_{12}$-deficiency resulted in increased plasma homocysteine (p<0.01), which was normalized by dietary supplementation of high-dose FA (p<0.01). However, FA supplementation and vitamin $B_{12}$ deficiency did not alter hepatic and brain S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) concentrations and hepatic DNA methylation. These results indicated that supplementation of high-dose FA improved homocysteinemia in vitamin $B_{12}$-deficiency but did not change SAM and SAH, the main biomarkers of methylating reaction.

CJ-50005(A형 간염백신)의 Rat 및 Dog에서의 단회투여독성 (Single Dose Toxicity Studies of C.1-50005 (Hepatitis A virus Vaccine) in Rats and Dogs)

  • 김종호;이성학;최재목;김달현;김현석;정용주
    • Toxicological Research
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    • 제17권4호
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    • pp.297-301
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    • 2001
  • The acute toxicity of CJ-50005, an inactivated whole virus vaccine derived from hepatitis A virus (HM175) grown in human MRC-5 diploid fibroblast culture, was tested in Sprague Dawley (SD) rats and beagle dogs. CJ-50005 was orally and intramuscularly administered up to the maximum dose of 81$\mu\textrm{g}$/kg. as much as 3,000 times of the expected clinical dose, in SD rats and was intramuscularly administered up to 27 $\mu\textrm{g}$/kg, as much as 1,000 times of the expected clinical dose, in beagle dogs. In these experiments, there were no death and clinical changes which were related to CJ-50005 administration. In addition, there were no significant changes between control and treated groups in body weights and autopsy findings. In conclusion, the administration of CJ-50005 over 81$\mu\textrm{g}$/kg in SD rats and over 27$\mu\textrm{g}$/kg in beagle dogs was proved to be safe, and it is thought that CJ-50005 may not show any toxicity in its clinical use.

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사용후핵연료 처리를 위한 ACP 핫셀의 정상운영 및 사고시 방사선 환경영향평가 (Radiation Dose Assessment of ACP Hotcell for Spent Fuel Treatment in Normal Operation & Accident Case)

  • 국동학;정원명;구정회;조일제;이은표;유길성
    • 방사성폐기물학회지
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    • 제2권3호
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    • pp.155-164
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    • 2004
  • 사용후핵연료의 효율적인 관리를 위하여 원자력연구소에서 개발중인 사용후핵연료 차세대관리 종합공정(ACP)은 공정타당성연구 단계를 마치고 이의 실증을 위한 $\alpha$-${\gamma}$ type핫셀 건설 단계에 이르렀다. 핫셀의 설계에 앞서 사용후핵 연료를 취급하게 되는 과정에서 발생할 수 있는 방사능에 대한 환경영향평가를 정상운전 시와 사고발생 시로 나누어 수행하였다. 평가에 필요한 자료들은 공정의 개념설계 보고서와 최근 연구소부지 기상 테이터 및 부지특성 자료를 바탕으로 하였으며 기존의 유사한 시설에 대한 평가방법을 참조하였다. 각 핵종별 발생량과 방출량을 계산하여 피폭선량을 계산하였으며 평가결과 원자력법관련 규제기준과 핫셀이 위치하게 되는 IMEF 건물의 안전성분석 기준보다 매우 안전한 결과를 얻어 시설 운영에 대한 안전성을 확보하였다.

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A Smart Setup for Craniospinal Irradiation

  • Peterson, Jennifer L.;Vallow, Laura A.;Kim, Siyong;Casale, Henry E.;Tzou, Katherine S.
    • 한국의학물리학회지:의학물리
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    • 제24권4호
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    • pp.230-236
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    • 2013
  • Our purpose is to present a novel technique for delivering craniospinal irradiation in the supine position using a perfect match, field-in-field (FIF) intrafractional feathering, and simple forward-optimization technique. To achieve this purpose, computed tomography simulation was performed with patients in the supine position. Half-beam, blocked, opposed, lateral, cranial fields with a collimator rotation were matched to the divergence of the superior border of an upper-spinal field. Fixed field parameters were used, and the isocenter of the upper-spinal field was placed at the same source-to-axis distance (SAD), 20 cm inferior to the cranial isocenter. For a lower-spinal field, the isocenter was placed 40 cm inferior to the cranial isocenter at a constant SAD. Both gantry and couch rotations for the lower-spinal field were used to achieve perfect divergence match with the inferior border of the upper-spinal field. A FIF technique was used to feather the craniospinal and spinal-spinal junction daily by varying the match line over 2 cm. The dose throughout the target volume was modulated using the FIF simple forward optimization technique to obtain homogenous coverage. Daily, image-guided therapy was used to assure and verify the setup. This supine-position, perfect match craniospinal irradiation technique with FIF intrafractional feathering and dose modulation provides a simple and safe way to deliver treatment while minimizing dose inhomogeneity.

Single Oral Dose Toxicity Studies of PGB-2, a Novel Polyglucosamine Polymer Produced from Citrobacter sp. BL-4 in Mice

  • Lee, Yong-Hyun;Son, Mi-Kyung;Jung, Young-Mi;Kim, Tae-Kwon;Park, Dong-Chan;Kim, Pan-Soo;Ku, Sae-Kwang
    • Toxicological Research
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    • 제23권1호
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    • pp.65-72
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    • 2007
  • This study was conducted to obtain information of the oral dose acute toxicity of PGB-2, a novel polyglucosamine polymer produced from Citrobacter sp. BL-4 (a new strain) in male and female mice. Mortality, body weight changes, clinical signs were monitored during 14 days after single oral dose of test article at dose levels of 2000, 1000, 500, 250 and 125 ml/kg. Gross lesions, organ weight and histopathology of principal organs were examined after necropsy. As the results, we could not find any mortalities, clinical signs, changes in the body weight and gross findings except for white foci in the liver. In addition, no PGB-2-treatment related abnormal changes on the organ weight and histopathology of principle organs were detected except for atypical signs of liver. White liver foci were confirmed as focal infiltration of inflammatory cells. The results suggest that the PGB-2 is relatively safe in mice but the possibility of hepatotoxicity could not be excluded. The $LD_{50}$ and approximate LD in mice after single oral dose of PGB-2 were considered over 2000 mg/kg, respectively. In future, the potential hepatotoxicity of PGB-2 should be evaluated through the repeat dose toxicity test prior to develop as a new agent.

Single Oral Dose Toxicity Study of Water Extracts of Picrorrhiza Rhizoma In ICR Mice

  • Lee Hyeung-Sik;Lee Ik-Gu;Ku Sae-Kwang
    • Toxicological Research
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    • 제22권2호
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    • pp.117-126
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    • 2006
  • This study was conducted to obtain the acute information of the oral dose toxicity of lyophilized water extract of Picrorrhiza Rhizoma (PR) - dried underground stem of Picrorrhiza kurroa, having various pharmacological effects, in male and female mice. In order to calculate 50% lethal dose ($LD_{50}$), approximate lethal dose and target organs, test article was administered once by oral gavage to male and female ICR mice at 2000, 1000, 500 and 250 mg/kg. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing with organ weight and histopathology of 12 types of principle organs. As the results, we could not find any mortality, clinical signs, changes in the body weight and gross findings except for hair loss, a significantly (p<0.05) increase of body weight gains in 2000mg/kg of PR extracts-dosing male group and some sporadic gross findings. In addition, no meaningful changes on the organ weight and histopathology of 12 types of principle organs were detected in the present study except for significantly (p<0.05) but dose independent changes on thymus, spleen and popliteal lymph nodes weights, and some sporadic accidental histopathological findings. The results obtained in this study suggest that the PR extract is non-toxic in mice and is therefore likely to be safe for clinical use. The $LD_{50}$ and approximate lethal dose of PR extracts in both female and male mice were considered as over 2000 mg/kg.

Efficacy and Safety of an Increased-dose of Dexamethasone in Patients Receiving Fosaprepitant Chemotherapy in Japan

  • Kumagai, Hozumi;Kusaba, Hitoshi;Okumura, Yuta;Komoda, Masato;Nakano, Michitaka;Tamura, Shingo;Uchida, Mayako;Nagata, Kenichiro;Arita, Shuji;Ariyama, Hiroshi;Takaishi, Shigeo;Akashi, Koichi;Baba, Eishi
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권1호
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    • pp.461-465
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    • 2014
  • Background: Antiemetic triplet therapy including dexamethasone (DEX) is widely used for patients receiving highly emetogenic chemotherapy (HEC). In Japan, the appropriate dose of DEX has not been established for this combination. Materials and Methods: To assess the efficacy and safety of increased-dose DEX, we retrospectively examined patients receiving HEC with antiemetic triplet therapy. Results: Twenty-four patients (fosaprepitant group) were given an increased-dose of DEX (average total dose: 45.8mg), fosaprepitant, and 5-HT3 antagonist. A lower-dose of DEX (33.6mg), oral aprepitant, and 5-HT3 antagonist were administered to the other 48 patients (aprepitant group). The vomiting control rates in the fosaprepitant and aprepitant groups were 100% and 85.4% in the acute phase, and were 75.0% and 64.6% in the delayed phase. The incidences of toxicity were similar comparing the two groups. Conclusions: Triplet therapy using an increased-dose of DEX is suggested to be safe and effective for patients receiving HEC.

Mouse Single Oral Dose Toxicity Studies of PGB-1, a Novel Polyglucosamine Polymer Produce from Enterobacter sp. BL-2

  • Lee, Yong-Hyun;Son, Mi-Kyung;Jung, Young-Mi;Kim, Tae-Kwon;Park, Dong-Chan;Lee, Hyeung-Sik;Kim, Pan-Soo;Ku, Sae-Kwang
    • Toxicological Research
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    • 제23권4호
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    • pp.373-382
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    • 2007
  • This study was conducted to obtain acute information of the oral dose toxicity of PGB-1, a novel polyglucosamine polymer produced from a new strain Enterobacter sp. BL-2 in male and female mice. In order to calculated 50% lethal dose ($LD_{50}$) and approximate lethal dose (LD), test material was once orally administered to male and female ICR mice at dose levels of 2000, 1000, 500, 250, 125 and 0 (vehicle control) ml/kg (body wt.). The mortality and changes on body weight, clinical signs, gross observation and organ weight and histopathology of principle organs were monitored 14 days after dosing with PGB-1. We could not find any mortalities, clinical signs, body weight changes and gross findings. In addition, significant changes in the organ weight and histopathology of principal organs were not observed except for some sporadic findings. The results obtained in this study suggest that PGB-1 may not be toxic in mice and may be therefore safe for clinical use. The $LD_{50}$ and approximate LD in mice after single oral dose of PGB-1 were considered over 2000 mg/kg in both female and male mice.

Single-dose Intravenous Injection Toxicity of Water-soluble Danggui Pharmacopuncture (WDP) in Sprague-Dawley Rats

  • Park, Sunju;Park, Hae-Mo;Sun, Seung-Ho
    • 대한약침학회지
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    • 제21권2호
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    • pp.104-111
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    • 2018
  • Objective:This study is to evaluate both the single-dose intravenous injection toxicity and the approximate lethal dose of Water-soluble Danggui Pharmacopuncture (WDP) in Sprague-Dawley (SD) rats. Methods: Toxicity experiments were conducted at Good Laboratory Practice (GLP) laboratory in Biotoxtech Co., according to the regulations of GLP. WDP injection of dose 0.125, 0.25, and 0.5 mL/animal were experimental groups and normal saline injection group was control group. WDP and normal saline were injected once to 6- week old 5 male and 5 female SD rats at the tail veins at approximately 2 mL/min. During 14 days after the injection, general symptoms were observed and weight were measured. After the observation period, hematological and blood biochemical examination, macroscopic autopsy, topical resistance test at the injection area were performed. Results: RThe WDP 0.5 mL/animal injection group in 4 cases of male rats and all cases of female rats showed hematuria 30 minutes after the administration. However, after 1 hour, no more abnormal general symptoms were observed. The WDP did not affect weight, hematological and blood biochemical examination, macroscopic autopsy, and topical resistance test at the injection area. Conclusion: WDP single dose intravenous injection results showed that WDP have no toxic effects and a lethal dose of WDP should be over 0.5 mL/animal in male and female rats under the study condition. So WDP may be safe.

Toxicity of Single-dose Intramuscular Injection of Samjeong Pharmacopuncture in Sprague-Dawley Rats

  • Kwon, Kang;Kim, Chul-Yun;Kim, Nam-Kwen;Sun, Seung-Ho;Seo, Hyung-Sik
    • 대한약침학회지
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    • 제18권2호
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    • pp.60-66
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    • 2015
  • Objectives: This study was carried out in order to find both the single-dose intramuscular injection toxicity and the approximate lethal dose of samjeong pharmacopuncture (SP) in Sprague-Dawley (SD) rats. Methods: The SD rats in this study were divided into four groups, one control group (1.0 mL/animal, normal saline) and three experimental groups (0.25, 0.5, and 1.0 mL/animal, SP). All groups consisted of five male and five female rats. SP was injected as a single-dose intramuscularly at the thigh. After the injection, general symptoms and weight were observed for 14 days. After the observations had ended, hematologic and serum biochemical examinations, necropsy and a local tolerance test at the injection site were performed. The experiments were carried out at the Good Laboratory Practice firm, Biotoxtech Co. (Cheongwon, Chungbuk). Animal experiments were approved by the Ethics Committee (Approval Number: 130379). Results: No deaths occurred in any of the three experimental groups. The injection of SP had no effects on the general symptoms, body weights, results of the hematologic, and serum biochemical examinations, and necropsy findings. In local tolerance tests at the injection sites, mild inflammation was observed in the experimental group, but it did not appear to be a treatment related effect. Conclusion: Under the conditions of this test, the results from the injection of SP suggest that the approximate lethal dose of SP is above 1.0 mL/animal for both male and female SD rats. Therefore, the clinical use of SP is thought to be safe.