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Objective: This study assessed the distribution of "lethal dose/pharmaceutical product strength" in high-risk drugs.Methods: In 707 pharmaceutical products (312 ingredients) that had been defined as high-risk drugs in Japan, we collected acute toxicity information from these products on single dose toxicity studies conducted in mice, including median lethal dose (LD50) and approximate lethal dose (aLD). The LD50 and aLD were then divided by the strength (quantity of active ingredients) of the pharmaceutical product, after which the LD50or aLD values having an inequality sign was excluded.Results: We collected data on the acute lethal dose of 707 products (312 ingredients) from high-risk drugs. Data with an inequality sign, which was 143 of 495 products (28.9%) in tablets and capsules, then 43 of 212 items (20.3%) in injections, were excluded from the analysis. As observed, median (Q1, Q3) of "LD50/pharmaceutical product strength" and "aLD/pharmaceutical product strength" for tablets or capsules was 36.8 tablet/kg (11.5 tablet/kg, 144 tablet/kg) and 16.7 tablet/kg (6.9 tablet/kg, 65 tablet/kg), respectively. However, median (Q1, Q3) of "LD50/pharmaceutical product strength" and "aLD/pharmaceutical product strength" for injections were 1.3 bottle/kg (0.6 bottle/kg, 4.7 bottle/kg) and 0.8 bottle/kg (0.4 bottle/kg, 15 bottle/kg), respectively. In both cases, injections were distributed at a lower value than oral products.Conclusion: From this study, the distribution of "lethal dose/pharmaceutical product strength" in high-risk drugs was clarified. This information will therefore help pharmacists assess risks associated with individual pharmaceutical products.
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Aims: The objective of this study is to identify S. suis type 2 and evaluate the virulence of ZHJ01 strain isolation, and verity the clinical and pathological outcome of a systemic infection caused by one serotype 2 when simultaneously inoculated with ZHJ01 strain. We also want to clarify the epidemiologic, clinical, microbiologic characteristics and the pathogenesis mechanism of S. suis type 2 in Hubei province, China. Study Design: Pigs suspected of being infected with S. suis in Jingzhou regions of Hubei province, China were studied. S. suis type 2 isolation was obtained from the suspicion of diseased pig. The case of S. suis type 2 was detected by the virulence factor amplification based on PCR detection and bacterial isolation, identification in the laboratory. According to the experimental infections of mice and piglets, pathogenicity of this S. suis type 2 isolation to mice and swine was monitored. This study was conducted in the key laboratory of pathogenic microbiology, College of Animal Science of Yangtze University, and Institute of Black Pigs Research, Yangtze University. Methodology: Proper serological typing can be performed using a co-agglutination test. The typical colonies purificated and cultured were inoculated with Glucose, Lactose, Raffinos, Sorbitol, D (+)-sucrose, Trehalose, 6.5%NaCl, D (-)-Salicin, Hippurate, Esculin hydrate, V-p, etc., then the test results were recorded. Detection of virulence factors were performed using PCR amplification and DNA sequencing. S.suis type 2 isolation was inoculated to mice and piglets for the virulence test, and the observation of the clinical signs and pathological changes. Results: The virulence factor of extracellular protein factor (EF) was determined from ZHJ01 strain based on PCR detection. Sequence analysis indicated that the isolate was very similar to nucleotide homology with others SS2 strains from different county or contries, and there was not much variation. LD50 of S. suis type 2 for mice was 2.5 x 107cfu. LD50 of S. suis type 2 for piglets was 3.92 x 109cfu. Conclusion: The results show that Swine S. suis type 2 has a relatively strong pathogenicity to pigs in Hubei province, China. This study can be, in part, sufficient to explain the pathogenicity for ZHJ01 strain in area of Zhijing, Jingzhou city, China, which may provide insights into the pathogenesis SS2 and more valid data to support the development of S. suis vaccine as well as the epidemiological investigation, further monitoring and effective prevention to S. suis.
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Objective • To investigate the effect of Toll-like receptor 4 (TLR4) in the pathological injury in fat embolism mice model. Methods • One hundred and twenty male C57BL/6 mice were randomly divided into 10 groups. One group was set as blank control group, and others were injected separately with 1, 2…9 μL/g of allogeneic perirenal fat via tail vein, respectively. The mortality of each group was counted, median lethal dose (LD50) of fat injection in mice was calculated by Bliss method, and the fat embolism LD50 mice model was established. The TLR4 protein expression in the pulmonary tissue of surviving mice was detected by Western blotting. Sixty male C57BL/6 mice were randomly divided into the control group (the same dose of saline was given via tail vein) and the experimental groups (group 2 h, group 8 h, group 24 h and group 48 h, the LD50 fat was given via tail vein). The TLR4 protein expression at different time after fat injection was detected by Western blotting. The mortality of 20 TLR4 gene-knockout mice (TLR4-/- mice) was recorded and compared with 60 wild-type mice after LD50 fat injection. Results • The LD50 of fat embolism mice model was (3.93±0.78) μL/g. After the injection of 1-7 μL/g fat, the expressions of TLR4 protein in the pulmonary tissue of all seven groups were significantly increased, compared with the control group (all P=0.000). In the fat embolism LD50 mice model, compared with the control group, the expressions of TLR4 protein in group 2 h were significantly increased (P=0.005). Then, expression level of TLR4 protein was gradually reduced after 2 h, and there was no significant difference between the control group and group 48 h. The mortality of TLR4-/- mice injected with LD50 fat was lower than that of wild-type mice (P=0.043). Conclusion • TLR4 protein involves in the pathologic process of fat embolism syndrome. The knockout of TLR4 gene can reduce the mortality of fat embolism mice. TLR4 and its correlated non-infectious inflammatory response may be an important molecular mechanism of biochemical injury in fat embolism syndrome. Blocking the activation of TLR4-mediated signaling pathway can significantly improve the prognosis, which provides new basis for the prevention, evaluation and treatment of fat embolism syndrome.
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Objective · To investigate the effect of Toll-like receptor 4 (TLR4) in the pathological injury in fat embolism mice model. Methods · One hundred and twenty male C57BL/6 mice were randomly divided into 10 groups. One group was set as blank control group, and others were injected separately with 1, 2…9 μL/g of allogeneic perirenal fat via tail vein, respectively. The mortality of each group was counted, median lethal dose (LD50) of fat injection in mice was calculated by Bliss method, and the fat embolism LD50 mice model was established. The TLR4 protein expression in the pulmonary tissue of surviving mice was detected by Western blotting. Sixty male C57BL/6 mice were randomly divided into the control group (the same dose of saline was given via tail vein) and the experimental groups (group 2 h, group 8 h, group 24 h and group 48 h, the LD50 fat was given via tail vein).The TLR4 protein expression at different time after fat injection was detected by Western blotting. The mortality of 20 TLR4 gene-knockout mice (TLR4-/-mice) was recorded and compared with 60 wild-type mice after LD50 fat injection. Results · The LD50 of fat embolism mice model was (3.93±0.78) μL/g.After the injection of 1-7 μL/g fat, the expressions of TLR4 protein in the pulmonary tissue of all seven groups were significantly increased, compared with the control group (all P=0.000). In the fat embolism LD50 mice model, compared with the control group, the expressions of TLR4 protein in group2 h were significantly increased (P=0.005). Then, expression level of TLR4 protein was gradually reduced after 2 h, and there was no significant difference between the control group and group 48 h. The mortality of TLR4-/- mice injected with LD50 fat was lower than that of wild-type mice (P=0.043).Conclusion · TLR4 protein involves in the pathologic process of fat embolism syndrome. The knockout of TLR4 gene can reduce the mortality of fat embolism mice. TLR4 and its correlated non-infectious inflammatory response may be an important molecular mechanism of biochemical injury in fat embolism syndrome. Blocking the activation of TLR4-mediated signaling pathway can significantly improve the prognosis, which provides new basis for the prevention, evaluation and treatment of fat embolism syndrome.