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In Vitro Regulatory Mechanism To Inflammatory Reaction Of Tulathromycin And Its Postantibiotic Effect (PAE) Against Actinobacillus Pleuropneumonia

Posted on:2009-06-21Degree:MasterType:Thesis
Country:ChinaCandidate:L ZhouFull Text:PDF
GTID:2143360245499150Subject:Prevention of Veterinary Medicine
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Tulathromycin is a novel macrolides antibiotic used in veterinary. Relative researches indicate that macrolides may exert immunomodulation effect through actions other than its antimicrobial properties. In order to understand whether the tulathromycin also does have the similar role, in vitro, we make use of the model that is LPS-induced porcine peripheral blood mononuclear cells (PBMC) overexpressed pro-inflammation factors, then apply the real-time Q-PCR to study the effect of different concentrations of tulathromycin and erythromycin on the generation of NO and PGE2 involved in the inflammatory process on the level of molecule. Compared to the concentration of 5μg/ml, 10 and 20μg/ml of tulathromycin significantly decreased the production of NO and PGE2, a similar pattern was also observed about the cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) gene transcription. However, all 5, 10 and 20μg/ml of erythromycin significantly decreased the production of NO and PGE2 at the transcription and expression level. These results support the opinion that macrolides may exert anti-inflammatory effect through modulating the synthesis of NO and PGE2 in inflammatory process. By com- pared with tulathromycin and erythromycin anti-inflammation efficacy, the rationality of 14-member ring macrolide antibiotics having stronger anti-inflammation activities than 15-member ring macrolide antibiotics have been proved. The results suggest that the atom number in Iactone ring is more important factor which influence the anti-inflammatory efficacy of macrolides. Porcine contagious pleuropneumonia (PCP) is an infectious procine respiratory tract disease causing severe economic losses worldwide in the swine industry, caused by Actinobacillus Pleuropneumoniae (APP). But with the widly long-term use of antibacterials, in many places of the world, the data showed that APP was different degree of resistance to commonly used antibiotics, such asβ-lactan and leucomycin and kanamycin etc. In recent years, an new theory: post-antibiotic effect (PAE) about pharmacodynamics of antibacterial agents has been proposed, it is for significance parameter which the reasonable design of dosage regimen of antiseptic drug needs. In this paper, from the determination of minimal inhibitory concentrations (MIC) of erythromycin and tulathromycin against APP by microdilution, and the determination of postantibiotic effects (PAE) of erythromycin and tulathromycin against APP by micro-inocualation colony counting, the results showed that the PAE of erythromycin against APP at the concentration of 1/2MIC, 1MIC, 2MIC and 4MIC was 0h, 0.15h, 0.20h and 0.40h, respectively; and the PAE of tulathromycin against APP at the concentration of 1/2MIC, 1MIC, 2MIC, 4MIC and 8MIC was 0.25h, 0.62h, 1.53h, 2.70h and 4.50h, respectively. It showed that postantibiotic effect induced by tulathromycin was obvious. It can be pointed out that when preparing a prescription of therapy by tulathromycin, we can prolong the medicine-administered interval time and reduce the number of times of administration, and the antibiotic effect can still maintain. These results indicate that the APP shows drug resistance to erythromycin, the PAE of erythromycin is not conspicuous; however, the APP is sensitive to tulathromycin, the PAE of tulathromycin is significant and has concentration-dependent manner. The results also show that PAE of tulathromycin is positively related to the drug concentrations in 4MIC and the time exposure to the bacteria, but negetively to the inoculum size. It can be pointed out that when preparing a prescription of therapy by tulathromycin, we can prolong the medicine-administered interval time and reduce the number of times of administration, and the antibiotic effect can still maintain.
Keywords/Search Tags:Tulathromycin, Inflammation factors, Regulatory mechanism, Postantibiotic effect (PAE)
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