• Title/Summary/Keyword: LD 50

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Experimental Studies on Korean Snake Venoms (한국산(韓國産) 사독(蛇毒)에 관(關)한 실험적(實驗的) 연구(硏究))

  • Kim, W.J.;Ahn, Y.S.;Kim, J.D.;Kim, S.W.;Hong, S.S.
    • The Korean Journal of Pharmacology
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    • v.12 no.2 s.20
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    • pp.33-41
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    • 1976
  • Agkistrodon halys (Crotalidae) is the only species of poisonous snakes in Korea, and is divided into three subspecies; Agkistrodon bromhoffii brevicaudus, Agkistrodon calaginosus and Agkistrodon saxatilis. With the three venoms, the pharmacological actions on the cardiovascular system and intestine as well as some toxicological characteristics were studied. In addition, the precipitin test in an agar gel medium was employed for immunological comparison of the venoms and the sera of envenomed patients. The results obtained were as follows: Lyophilized venoms contained solids of $211{\sim}273mg/ml$, and LD50 to mice were 1.73 and 0.86 mg/kg in venoms of Agkistrodon bromhoffii brevicaudus obtained on July and October respectively, and 0.40 and 0.32 mg/kg in Agkistrodon calaginosus and the venoms of Agkistrodon saxatilis obtained on October was 2.29 mg/kg. Isoelectric focusing of lyophilized snake venoms showed 19 to 22 protein fractions and 2 to 3 isoamylase fractions. Acute irreversible hypotension was caused by the intravenous injection of large doses of venoms in rabbits and cats, but at the small doses, acute hypotension followed by slow recovery. Little changes of cardiac movements by the venom injection despite of marked hypotension were showed except bradycardia and arrhythmia prior the death. Also no changes on the isolated rabbit atria by the snake venoms were noted. The hypotensive effect of the snake venoms was prevented by the bilateral vagotomy or atropine pretreatment (1 mg/kg), but they did not affect when already the hypotension has undergone. In the isolated rabbit duodenum, small doses of venom increased the phasic movement, while large doses decreased after spastic contraction. With the injection of venoms in dog, strong contraction of gall-bladder was caused and it was not blocked by the pretreatment with phenoxybenzamine (10 mg/kg) or atropine (1.4 mg/kg). In the venoms of Agkistrodon bromhoffii brevicaudus and Agkistrodon calaginosus, at least 5 antigenic components were detected, and four of them were shared in common with each other. Polyvalent antivenin (Wyeth Lab. USA) had three common precipitating antibodies with the venom of Agkistrodon bromhoffii brevicaudus and Akistrodon calaginosus. In the serum of envenomed patients, no precipitating antibodies were seen to the venoms and little changes in serum protein, GOT and GPT were observed. In conclusion, the snake venoms obtained in Korea were highly toxic and caused chiefly the vascular collapse leading to death. This vascular collapse was resulted largely by cholinergic effects, and not cardiotoxin of venoms. In human, it is likely that precipitating antibodies to venom were not produced by an envenomed incidence to poisonous snakes.

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Anti-fatigue and Hepatoprotective Activities of Nokyangbotang (녹양보탕의 항피로 및 항산화작용)

  • 김창종;김현준;이윤혜;이연아;이정근;문성원;박진형;장용운;조중형
    • YAKHAK HOEJI
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    • v.44 no.3
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    • pp.224-231
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    • 2000
  • $Nokyangbotang^{TM}$ (NYBT) is a kind of powerful food for health and have been drunk at a oral dose of 80 ml (99.5 mg) three times per day: It has not been well studied about the anti-fatigue and hepatoprotective activity. In this experiments, we evaluated pathophysiologically the effect of NYBT on swimming time in mouse and hepatoprotective activity in rats intoxicated with carbon-tetrachloride. NYBT was nontoxic in orally acute toxicity test ($LD_{50}$, 320 ml/60 kg): a nontoxic food in more four times of one-shoot dosage (80 ml) to human. Weight-loaded forced swimming test was carried out to measure the swimming time of mice with a 4% load of body weight in plastic cylinder (diameter $10{\;}cm{\;}{\times}{\;}height{\;}20{\;}cm$) on water bath at $25^{\circ}C$, and the anti-fatigue activity represented the ratio of swimming time of experimental group to that of control group. NYBT had dose-dependent anti-fatigue activity Mice administered NYBT at a dose of 320 ml/60 kg once daily for 5 days could swim about two times more than control. Hepatoprotective activities of NYBT were examined by the determination of malonedialdehyde (MDA) and pathological survey in liver and liver function test of rat intoxicated with $CCl_4$ at i.m. dose of 2 ml/kg once daily for 7days. NYBT decreased dose-dependently thiobarbituric acid reactive substance: Oral administration of NYBT at a dose of 20 ml/60 kg was $38.51{\;}{\pm}{\;}3.02$ nmol MDA/g of tissue, that of 80 ml/60 kg was $33.76{\;}{\pm}{\;} 1.84$ nmol MDA/g of tissue, and that of 320 ml/60 kg was $32.87{\;}{\pm}{\;}1.90$ nmol MDA/g of tissue as compared with control group ($43.61{\;}{\pm}{\;}2.85$ nmol MDA/g of tissue). All rats administered NYBT at a dose of 320 ml/60 kg were survival as compared with 40% survival of control animals, and GPT activity of rats administered NYBT at a dose of 80 ml/60 kg was decreased as compared with control. In histopathological survey, NYBT improved slightly the fatty changes of hepatocytes around centrilobular area. These results suggest that NYBT has anti-fatigue and hepatoprotective activity in rats and mice.

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A Study on Single Oral Dose Toxicity of Highly-Developed Anthocyanin-Pigmented Rice Varieties (생리활성이 우수한 고품질 유색미의 단회 경구투여 안전성 연구)

  • Han, Hye-Kyoung;Choi, Sung-Sook;Shin, Jin-Chul;Chung, Ha-Sook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.36 no.5
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    • pp.527-533
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    • 2007
  • The present study was carried out to investigate the potential toxicity of highly-developed rice varieties, Oryza sativa cvs. Jukjinjubyeo, Heuginjubyeo and Heughyangbyeo by a single oral dose in ICR mice. The test article was orally administered once by gavage at dose levels of 0, 2.5, 5.0, and 10.0 g/kg body weight (n=10 for male and female mice for each dose). We examined the number of deaths, general clinical signs, body weights and biochemical analysis for sexes and doses of mice between control and experimental groups. As a result all of the groups were alive during experimental periods and none of the significant clinical symptom and body weight changes were shown in all of the groups. Plasma glucose levels were valued for both control and experimental groups and there were no significant differences between the groups. The activities of aminotransferase were not increased in all experimental groups compared to control groups. The results suggest that the toxicity of the aleurone layer of Oryza sativa cvs. Jukjinjubyeo, Heugjinjubyeo and Heughyangbyeo are low and its $LD_{50}$ is over 10.0 g/kg body weight in both male and female mice.

Anti-Obesity Activity, Anti-Cancer Activity and Single Oral Dose Toxicity of Inonotus xeranticus Extracts (기와층버섯 추출물의 항비만활성, 항암활성 및 단회경구독성시험)

  • Kang, Eun-Hee;Lee, In-Kyoung;Hwang, Mi-Hyun;Choi, Jae-Young;Chang, Zhi-Qiang;Rhee, Man-Hee;Yun, Bong-Sik;Jiang, Cheng-Zhe;Kim, Kil-Soo;Park, Seung-Chun
    • Toxicological Research
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    • v.23 no.3
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    • pp.253-261
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    • 2007
  • In this study, we investigated the in vitro anti-obesity, anti-cancer activity and single oral dose toxicity of Inonotus xeranticus extracted by methanol (INXM) or ethyl acetate (INXE). In order to investigate anti-obestity effect of Inonotus xeranticus extracts, the 3T3-L1 cells were treated with these extracts at various concentrations(1, 10, 100 and $300{\mu}g/ml$). It was observed that 3T3-L1 cells treated with $100{\mu}g/ml$ of Inonotus obliquus ethyl acetate extract (INOE), INXM and INXE, in the absence of differentiation cocktail (0.5mM isobutylmethylxanthine (IBMX) $1{\mu}M$ dexamethasone, $1{\mu}M$ insulin), differentiated at a rate of 78.5, 80.9, and 76.4% respectively. Differentiation rates of 86.6% and 83.4% were observed in 3T3-L1 cells which were treated with differentiation cocktail at $100{\mu}g/ml$ of INXM and INXE, respectively. The anti-cancer effect of Inonotus xeranticus extracts was investigated using a method of sulforhodamine B in sarcoma 180 cell line. The cells were treated with these extracts (1, 10, 100 and $300{\mu}g/ml$) for 48 hours. The growth of cells which were treated with $300{\mu}g/ml$ of INXM was inhibited by 80.1%. The growth of sarcoma 180 cells which were treated with 100 and $300{\mu}g/ml$ of INXE was inhibited by 74.7% and 64.5%, respectively. In single oral dose toxicity study, no differences were observed between control and treated groups in clinical signs, body weight gains, and feed and water consumptions. The results indicated that Inonotus xeranticus extracts did not show any toxic effects at 2,000mg/kg in mice, and the $LD_{50}$ of these extracts was found to be higher than 2,000 mg/kg in this experiment. From the above results, Inonotus xeranticus methanol and ethyl acetate extracts might have useful clinical applications in the management of cancer and obesity and may also be useful as a medicinal food.

Pathogenicity of Salmonella gallinarum isolated from chickens in Korea (국내 분리주 Salmonella gallinarum의 닭에 대한 병원성)

  • Lee, Hee-soo;Kim, Soon-jae;Kim, Ki-seuk;Mo, In-pil;Kim, Tae-jong
    • Korean Journal of Veterinary Research
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    • v.37 no.3
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    • pp.569-576
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    • 1997
  • Fowl typhoid(FT) caused by Salmonella gallinarum is an infectious, egg-transmitted disease and characterized by swollen bronze liver, greenish-yellow diarrhea and high mortality in growing and adult chickens. Since 1992 the outbreak of FT has been increased. Several problems have been occurred such as absence of appropriate vaccines and lack of useful therapeutic methods. In these studies we investigated the pathogenicity of S gallinarum isolated in chickens. To compare the pathogenicity among the species of chickens, all chickens were challenged intramuscularly or orally with $1{\times}10^7$ CFU of S gallinarum. The brown-colored layers were more susceptible and white leghone chickens were more resistant than other species. In the brown layer chickens orally challenged, lethal doses ($LD_{50}$) of the isolates were inoculated at 1 day, 2 weeks, 4 weeks and 8 weeks old chickens with amount of $10^{4.2}$, $10^{4.7}$, $10^{7.0}$ and $10^{7.6}$ CFU, respectively. The chickens which were intramuscularly challenged with the less amount than $10^2$ CFU showed higher mortality than that of the chickens orally inoculated with same dose. Also, we investigated the recovery rates of bacteria from various organs of survival chickens which were challenged orally with $5{\times}l0^7$ CFU of S gallinarum. The bacteria was more frequently and isolated earlier from the liver and spleen than from any other ogans. In the pathogenicity test, the white-leghorn chickens which were known as resistant-strain against Salmonella were artificially immunosuppressed using bursectomy and/or dexamethasone treatment. Mortality of chickens with both bursectomized and treated with dexamethasone was higher(90%) than that of the control group(10%), the bursectomized chickens(10%) and the dexamethasone only treated group(20%). It was suggested that the protective mechanism in chickens against S gallinarum may be required both the functions of B-cells and T-cells.

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Identification and Characterization of the Vibrio vulnificus malPQ Operon

  • LIM MOON SUB;LEE MYUNG HEE;LEE JEONG HYUN;JU HYUN-MOK;PARK NA YOUNG;JEONG HYE SOOK;RHEE JEE EUN;CHOI SANG HO
    • Journal of Microbiology and Biotechnology
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    • v.15 no.3
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    • pp.616-625
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    • 2005
  • It is likely that maltose could provide a good substrate for the bacteria in the intestine, when the pathogenic bacteria invade and colonize in human gut. For better understanding of this organism's maltose metabolism, a mutant that was not able to grow with maltose as a sole carbon source was screened from a library of mutants constructed by a random transposon mutagenesis. By a transposon-tagging method, malPQ genes encoding a maltodextrin phosphorylase and a 4-${\alpha}$-glucanotransferase, were identified and cloned from Vibrio vulnificus. The deduced amino acid sequences of malPQ from V. vulnificus were 48 to $91\%$ similar to those of MalP and MalQ reported from other Enterobacteriaceae. Functions of malPQ genes were assessed by the construction of mutants whose malPQ genes were inactivated by allelic exchanges. When maltose was used as the sole carbon source, neither malP nor malQ mutant was able to grow to a substantial level, revealing that the MalP and MalQ are the only enzymes for metabolic utilization of maltose. The malQ mutant exhibited decreased adherence toward intestinal epithelial cells in vitro, but there was no difference in the $LD_{50}s$ of the wild-type and the malQ mutant in mice. Therefore, it appears that MalQ is less important in the pathogenesis of V. vulnificus than would have been predicted by considering maltose as a most common sugar in the intestine, but not completely dispensable for virulence in mice.

Examinations on sedation, anaesthetic and toxic effect of Isoeugenol for olive-flounder (Paralichthys olivaceus) (Isoeugenol의 넙치(Paralichthys olivaceus)에 대한 진정, 마취 및 독성효과 검토)

  • Shin, Gee-wook;Shin, Yong-seung;Kim, Young-rim;Lee, Eun-young;Yang, Hyang-hee;Palaksha, K.J.;Huh, Nam-eung;Yeon, Seong-chan;Lee, Hee-chun;Oh, Myung-ju;Joh, Seong-joon;Kang, Seung-won;Jung, Tae-sung
    • Korean Journal of Veterinary Research
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    • v.45 no.2
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    • pp.303-309
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    • 2005
  • Olive flounder (Paralichthys olivaceus) is the major mariculture fish in Korea. The annual aquaculture production of olive flounder in Korea during the period of 2003 was 300,000 ton (2002 Statistics, Ministry of Maritime Affairs & Fisheries, Korea Government). Anesthetics is very necessary in aquaculture to minimize stress and damage during harvesting, grading, transportation, spawning induction and handling to fish. In the present study, isoeugenol as new anesthetic in marine fish, especially olive flounder, was examined to know the efficacy and proper concentration. As a result, olive flounder adult was exhibited sedation at 5 ppm at 10 and $15^{\circ}C$, and 7.5 ppm at $20^{\circ}C$, respectively. Anesthesia was required at least 10, 7.5 and 10 ppm at $10^{\circ}C$, $15^{\circ}C$ and at $20^{\circ}C$, respectively. In case of fry, the effect of sedation was observed from 2.5 ppm at $10^{\circ}C$ and 5 ppm at 15 and $20^{\circ}C$, respectively. Anesthesia was observed from 2.5 ppm at $10^{\circ}C$, 5 ppm at 15 and $20^{\circ}C$, respectively. In acute toxicity test, it was impossible to explore $LD_{50}$ with the concentration of isoeugenol adult at $15^{\circ}C$ used, but over immersion volume of 15 ppm at $15^{\circ}C$ was observed mortality in fry. Based on the present study, isoeugenol was identified as a safe and active anesthetic to olive flounder.

Improving Stability and Characteristic of Circuit and Structure with the Ceramic Process Variable of Dualband Antenna Switch Module (Dual band Antenna Switch Module의 LTCC 공정변수에 따른 안정성 및 특성 개선에 관한 연구)

  • Lee Joong-Keun;Yoo Joshua;Yoo Myung-Jae;Lee Woo-Sung
    • Journal of the Microelectronics and Packaging Society
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    • v.12 no.2 s.35
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    • pp.105-109
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    • 2005
  • A compact antenna switch module for GSM/DCS dual band applications based on multilayer low temperature co-fired ceramic (LTCC) substrate is presented. Its size is $4.5{\times}3.2{\times}0.8 mm^3$ and insertion loss is lower than 1.0 dB at Rx mode and 1.2 dB at Tx mode. To verify the stability of the developed module to the process window, each block that is diplexer, LPF's and bias circuit is measured by probing method in the variation with the thickness of ceramic layer and the correlation between each block is quantified by calculating the VSWR In the mean while, two types of bias circuits -lumped and distributed - are compared. The measurement of each block and the calculation of VSWR give good information on the behavior of full module. The reaction of diplexer to the thickness is similar to those of LPF's and bias circuit, which means good relative matching and low value of VSWR, so total insertion loss is maintained in quite wide range of the thickness of ceramic layer at both band. And lumped type bias circuit has smaller insertion itself and better correspondence with other circuit than distributed stripline structure. Evaluated ceramic module adopting lumped type bias circuit has low insertion loss and wider stability region of thickness over than 6um and this can be suitable for the mass production. Stability characterization by probing method can be applied widely to the development of ceramic modules with embedded passives in them.

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Effects of Lycii fructus extract on Experimentally Induced Liver Damage and Alloxan Diabetes in Rabbits (구기자(枸杞子) 추출물(抽出物)이 가토(家兎)의 실험적(實驗的) 간장장애(肝臟障碍) 및 alloxan당뇨병(糖尿病)에 미치는 영향(影響))

  • Sheo, Hwa-Joong;Jun, Sung-Joo;Lee, Myung-Yul
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.15 no.2
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    • pp.136-143
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    • 1986
  • These studies were carried out to investigate effects of Lycii fructus extract on experimentally CC14-induced liver damage and alloxan-induced diabetes in rabbits and acute toxicity using mice. $LD_{50}(mg/kg)$ of Lycii fructus extract(L.F.E.) was 12.17g/kg by intraperitoneal administration in mice. L.F.E. showed more rapid recuperation compared to the control group in CC14-intoxicated rabbits and 800mg/kg was the most effective. Especially GPT activity and total bilirubin level showed an apparant decreasing effect within 6 days and 8 days, respectively in 800mg/kg. But any differences were not observed in alkaline phosphatase and total cholesterol between sample and control group. Large amount administered group exhibited more excellent hypoglycemic effect in alloxan-induced diabetes of rabbits, that is, it was significant to the control group after 4 days and adjacent to the normal level on 12th day. And GPT activity was gradually decreased and showed clear decreasing effect after 6 days. It is suggested that L.F.E. can be administered not only as therapeutic agents (such as liver tonics or antidiabetetics) but also a natural food to shorten the recovery time of hepatic function in liver diseases and decrease the abnormally elevated blood glucose such as Diabetes Mellitus.

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Acute Toxicity of Leuconostoc Citreum GR1 Isolated from Kimchi in Mice (김치로부터 분리한 Leuconostoc citreum GR1의 마우스에 대한 급성독성)

  • Lee, Hwan;Cha, Seon-Suk;Lee, Myung-Yul;Chang, Hae-Choon;Lee, Jae-Joon
    • Food Science and Preservation
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    • v.20 no.1
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    • pp.121-126
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    • 2013
  • The present study was carried out to investigate the in vivo single-dose acute toxicity of Leuconostoc citreum GR1 (Leuc. citreum GR1), a lactic acid bacteria isolated from kimchi, in ICR male and female mice. The test article was orally administered once to both sexes of mice. The mortalities, clinical findings, autopsy findings, and body weight changes were monitored daily for two weeks. The male and female mice were gavaged with Leuc. kimchi GR1 of four doses (625, 1,250. 2,500 and 5,000 mg/kg). The oral $LD_{50}$ of Leuc. citreum GR1 was considered higher than 5,000 mg/kg. No significant changes in the general conditions, body weights, clinical signs and presence of gross lesions were observed in both sexes of mice to whom Leuc. citreum GR1 was administered orally. The results indicated that the 5,000 mg/kg dose of Leuc. citreum GR1 showed no adverse effect.