• Title/Summary/Keyword: LD$^{50}$

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The Purification and Immunogenicity of Pneumococcal Surface Protein (PspA) from Invasive Streptococcus pneumoniae KNIH1156 Isolated in Korea (국내 임상 분리주 Streptococcus pneumoniae KNIH1156으로부터 PspA 단백 항원의 정제 및 면역원성 확인)

  • 정경석;배송미
    • Korean Journal of Microbiology
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    • v.38 no.1
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    • pp.38-44
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    • 2002
  • Pneumococcal surfacce protein A (PspA) is an important virulence factor and an antigenically variable surface protein of the pneumococci. To purify the PspA from S. pneumoniae KNIH1156 , a clinical isolate (type 19F), we have taken advantage of the fact that PspA is released from the surface of pneumococci into the medium by growing in a CDM-ET medium and PspA is capable of binding human lactoferrin, the iron carrier protein. PspA of S. pneumoniae KNIH1156 was purified from culture supernatant by human lactoferrin (hLf) affinity chromatography. The purified PspA was confirmed with anti-PspA antiserum and also had the binding capacity to hLf specifically. To determine whether the purified PspA could elicit protection in mice against pneumococcal inflection, we immunized the mice with purified PspA and subsequently challenged with S. pneumoniae KNIH1156. Immunization with purified PspA protected mice from 500 times the $LD^{50}$ of S. pneumoniae KNIH1156. Therefore, it has been shown that purified PspA fromS. pneumoniae KNIH1156 (type 19F) is a protective immunogen.

Stability and Bioavailability on Prodrug of 5-Flurouracil (I). Synthesis, Physicochemical Properties, Stabilities and Antitumor Activities of 1-Glycyloxymethyl-5-fluorouracil Hydrochloride (5-Fluorouracil의 Prodrug에 대한 안정성 및 생체이용율에 관한 연구(I). 1-Glycyloxymethyl-5-fluorouracil HCl의 제조, 물리화학적 성질, 안정성 및 항암효과)

  • Jee, Ung-Kil;Lee, Gye-Won;Park, Mork-Soon
    • Journal of Pharmaceutical Investigation
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    • v.22 no.3
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    • pp.185-196
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    • 1992
  • To assess its suitability as a prodrug of 5-fluorouracil (5-FU), 1-glycyloxymethyl-5-FU HCl (GFU), a 5-fluorouracil derivative having a glycyloxymethyl group at the N-l position was synthetized. Its physicochemical properties and hydrolysis kinetics, in aqueous solution of pH $1{\sim}10$ and in the presence of human plasma or rat liver homogenate were studied. Its acute toxicity and antitumor activity against sarcoma 180 were also examined, GFU showed higher lipid/water partition coefficient than 5-FU. The calculated $pK_{\alpha}$ values of 5-FU and GFU were 8.02 and 7,20, respectively. The decomposition rates of GFU in aqueous solution showed a pH-dependence over the pH range used, which could be ascribed to solvent catalysed hydrolysis reaction at pH lower than 4,16 and to specific hydroxide ion hydrolysis reaction at pH higher than 4,16, The half-life of GFU was 6,9 min in 80% human plasma solution and less than 3 min in rat liver homogenate at $37^{\circ}C$, The $LD_{50}$ value of 5-FU was 240 mg/kg while that of GFU was 440.6 mg/kg (226 mg as 5-FU). Both of 5FU and GFU showed a strong antitumor activity, Therapeutic ratios of 5-FU and GFU were 3.07 and 3.55, respectively.

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Acute Toxicity Study of Poly(sodium acrylic acid-acrylic acid) in Rats and Mice (랫드와 마우스에서 폴리(아크릴산 소다-아크릴산)의 급성 경구 독성 시험에 관한 연구)

  • 박기숙;서경원;김효정
    • Journal of Food Hygiene and Safety
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    • v.8 no.2
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    • pp.97-103
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    • 1993
  • The acute toxicity of orally administered poly(sodium acrylic acid-acrylic acid), powerfully water-absorbent polymer, was el'aluated in Sprague-Dawley rats and feR mice. Rats and mice aging 6 weeks were gavaged with 0, 2.0, 3.0, 4.4, 6.7, or 10 g of poly(sodium acrylic acidacrylic acid)/kg in com oil. No animal died by treatment and any toxic symptom was not observed in the treated animals during 2 weeks. The body weight of the treated animals was not significantly different from the controls. The results of macroscopic examination on the organs of the treated animals revealed no abnormal findings. Therefore, it was concluded that poly(sodium acrylic acidacrylic acid) was practically non-toxic when it was orally administrated to rats and mice up to 10 g/kg, and its $LD_{50}$ was evaluated more than 10 g/kg in rats and mice.

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Acute Toxicity Study of the Hwangryunhaedok-tang Extract in ICR Mice (황련해독탕(黃連解毒湯) 열수 추출물의 급성독성 연구)

  • Lee, Ji-Hye;Eum, Hyun-Ae;Chung, Tae-Ho;Lee, Yoon-Hee;Um, Young-Ran;Yim, Nam-Hui;Kim, Dong-Seon;Ma, Jin-Yeul
    • Herbal Formula Science
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    • v.18 no.2
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    • pp.159-166
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    • 2010
  • Objective : The objective of this study was to evaluate the single dose oral toxicity of Hwangryundaedok-tang extract in ICR mice. Methods : 0(control group), 1250, 2500 and 5000 mg/kg of Hwangryundaedok-tang extracts were orally administered to 20 male and 20 female ICR mice. After single oral administration of Hwangryundaedok-tang extract to ICR mice, we observed number of the death, clinical signs, changes of body weights for 14 days. After 14 day of Hwangryundaedok-tang extract administration, all mice were sacrificed and major organs were observed. Results : Compared with the control group, we could not find any toxic signs in the mortalities, clinical signs, body weight changes, necropsy findings and hematological values in all treated groups(1250, 2500 and 5000 mg/kg). Conclusions : $LD_{50}$ value of Hwangryundaedok-tang extracts may be over 5000 mg/kg and it may have no side toxic effect to ICR mice.

Acute Toxicity Study on Socheongryong-Tang and Fermented Socheongryong-Tang extracts in Mice (소청룡탕 및 발효 소청룡탕 추출물의 단회투여 독성에 관한 연구)

  • Lee, Ji-Seon;Hwang, Youn-Hwan;Lee, Ji-Hye;Oh, Su-Young;Kim, Tae-Soo;Ma, Jin-Yeul
    • The Korea Journal of Herbology
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    • v.26 no.4
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    • pp.101-107
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    • 2011
  • Objectives : Socheongryong-Tang (小靑龍湯, SCRT) has been widely used to treat respiratory disease. In this study, we investigate the acute toxicity and safety of fermented Socheongryong-Tang extract. Methods : To evaluate the acute toxicity and safety, 0 (control group), 1250, 2500 and 5000 mg/kg of Socheongryong-Tang and fermented Socheongryong-Tang extracts were orally administered to male and female ICR mice. After single administration, we observed survival rates, general toxicity, changes of body weight for the 14 days and autopsy. Results : Compared with the control group, we could not find any toxic alteration in all treated group (1250, 2500 and 5000 mg/kg). Conclusions : $LD_{50}$ of Socheongryong-Tang and fermented Socheongryong-Tang extracts might be over 5000 mg/kg and it is safe to ICR mice.

Acute Oral Toxicity of Alismatis Rhizoma in SD Rats (택사(Alismatis Rhizoma) 추출물의 급성 경구투여 독성 연구)

  • Seok, Ji-Hyun;Roh, Hang-Sik;Jeong, Ja-Young;Ha, Hun-Yong
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.26 no.4
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    • pp.15-25
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    • 2013
  • Objectives : This study was carried out to evaluate the acute oral toxicity of Alismatis Rhizoma in Sprague-Dawley(SD) rats. Methods : male and female rats were administered orally with Alismatis Rhizoma water extract of 1,000 mg/kg (low dosage group), 2,000 mg/kg(middle dosage group) and 4,000 mg/kg(high dosage group). We daily observed number of deaths, clinical signs and gross findings for 7 days. After 7 days, we measured body and organs weight. Also we analyzed hematological changes. Results : No dead SD rats and no clinical signs were found during the experiment period. Also other specific changes were not found between control and treated groups in hematology and serum biochemistry. In addition no significant changes of gross body and individual organs weight. Conclusions : These results suggest that water soluble extract of Alismatis Rhizoma has not acute oral toxicity and oral $LD_{50}$ value was over 4,000 mg/kg in SD rats.

Acute Toxicity of Palatinose and Palatinose Syrup in Rats (팔라티노스 및 팔라티노스 시럽의 Rat 에서 급성 독성)

  • Lim, Dong-Moon;Lee, Seong-Hak;Kim, Dal-Hyun;Cho, Hyo-Jin;Kim, Jeong-Hwan;Chun, Young-Jung;Kim, Je-Hak
    • Korean Journal of Food Science and Technology
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    • v.29 no.4
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    • pp.800-803
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    • 1997
  • The acute toxicity of palatinose and palatinose syrup was assessed in Sprague-Dawley rats. Palatinose and palatinose syrup, when administered orally at the doses of 27 g/kg, did not cause any death. Although the decrease in weight gain was observed in males treated with palatinose syrup, it did not have any toxicological importance. There were no significant changes in hematological and biochemical parameters. From these results, it was concluded that palatinose and palatinose syrup did not induce any remarkable toxicological symptoms and the $LD_{50}$ is >27 g/kg by oral administration in Sprague-Dawley rats.

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In Vivo Immunotoxicities of Butylated Hydroxyanisole (BHA) and Butylated Hydroxytoluene (BHT) in Male Mice

  • Moon, Chang-Kiu;Lee, Soo-Hwan;Park, Kwang-Sik;Hwang, Gwi-Seo;Mock, Myung-Soo;Chung, Dong-Seok;Kim, Dae-Dok;Min, Seok-Ki
    • Archives of Pharmacal Research
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    • v.10 no.4
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    • pp.223-227
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    • 1987
  • The effects of butylated hydroxyanisole and butylated hydroxytoluene on the immune status in normal male were evaluated. They exhibited significant decrease in the circulating leukocyte counts. Relative spleen and thymus weights were slightly decreased, but not stratistically significant. These were, however, significant liver hypertrophies in theier exposed mice. Splenic IgM PFCs per one million cells in 1/20 LD50 BHA and BHT exposed mice were significantly reduced IgM PFCs per spleen were similar tothose of control, except in 1/20 LD50 BHA exposed mice, where they were significantly suppressed. The precise nature of the inhibition is not clear. Direct cytotoxicity is not responsible for the depressed antibody response, even following relatively high doses of them, because the changes in spleen cellularity are not significant. Both substances, however, did not show any effects on the arthus reaction and delayed hypersensitivity reaction induced by heat aggreagted bovine serum albumin, and in vivo phagocytosis of colloidal carbon. In the light of the present results, in vivo antibody response as well as in vitro, may be sensitive to BHA of the present results, in vivo antibody response as well as in vitro, amy be sensitie to BHA and BHT. Further elucidation of the precise nature of antibody suppression in their exposed mice, is warranted.

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Syntheses of Biologically Active Phosphinate Derivatives with a Pendant Monoazacrown Ether (모노아자크라운에테르 기능기를 가진 생리활성 포스피네이트 유도체의 합성)

  • Nam Chong-Woo;Chung Yeong-Jin;Yang Il-Woo
    • Journal of the Korean Chemical Society
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    • v.37 no.1
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    • pp.154-161
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    • 1993
  • Four kinds of new phosphinate derivatives with a pendant monoazacrown ether were synthesized and their biological activities were tested. These biologically active phosphinates were synthesized in relatively good yields (61∼72%) by one step reactions of phenylphosphinate with aldehyde and monoazacrown ether. Toxicity of these compounds was tested by intraperitoneal injection of the compounds to male mouse and revealed $LD_{50}$ value of 65∼90 mg/kg, which showed enhanced toxicity by attachment of a pendant azacrown ether to a simple phenylphosphinate structure. Although the ring size effect of the pendant crown ethers, (monoaza-15-crown-5 and monoazo-18-crown-6), beening negligible, the identity of the ester functional group in the phosphinate structure exerted sizable influence on toxicity. Thus, phosphinate derivative with octyl or propyl ester group showed somewhat higher toxicity than that with ethyl ester group.

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Inhibition of Tumor Growth and Angiogenesis by KJ3, Betulinic Acid, and Fumagillin in Mouse Neuroblastoma (신생혈관 억제제 KJ3, Betulinic acid, Fumagillin의 혈관형성억제 및 신경모세포종에 대한 치료효과)

  • Choi, Seung-Hoon;Lee, Jung-Hee;Hwang, Eui-Ho
    • Advances in pediatric surgery
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    • v.8 no.2
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    • pp.101-106
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    • 2002
  • The antiangiogenic effects of novel agent KJ3, Betulinic acid, and Fumagillin on the neovascularization were studied by examining ultrastructural alterations in the vasculature of synthetic gelform and mouse neuroblastoma C1300. Small pieces of gelform with 0.4% agar were introduced subcutaneously (s.c.) in 7 week old male CH3/HeJ mice. After the $LD_{50}s$ were determined by FACS analysis, a third of $LD_{50}$ of three drugs were injected either locally or intraperitoneally every other day for 14 days. A/J mice were inoculated s.c. with the C1300 neuroblastoma cell line, then either saline or three drugs were injected in the same manner. The antiangiogenic effects of three drugs were studied by measuring the histologic changes in tumors, and immunostaining for CD34, VIII/vWF, CD105, and thymidine phosphorylase. In the drug treated groups, the number of vessels in gelform experiments and C1300 neuroblastoma experiments were lower than the corresponding values in the control. The histologic findings were significantly different in drug treated groups on day 7, but these were not significant on day 14. These results imply that antiangiogenic agents were effective when the tumor burden is minimal.

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