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测试抗菌肽在大鼠诱导性骨髓炎局部治疗中的疗效。

Testing the efficacy of antimicrobial peptides in the topical treatment of induced osteomyelitis in rats.

作者信息

Melicherčík Pavel, Čeřovský Václav, Nešuta Ondřej, Jahoda David, Landor Ivan, Ballay Rastislav, Fulín Petr

机构信息

Department of Orthopaedics, First Faculty of Medicine, Charles University in Prague and Motol University Hospital, V Úvalu 84, 150 06, Prague 5, Czech Republic.

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo náměstí 2, 166 10, Prague 6, Czech Republic.

出版信息

Folia Microbiol (Praha). 2018 Jan;63(1):97-104. doi: 10.1007/s12223-017-0540-9. Epub 2017 Aug 2.

Abstract

Joint replacement infections and osteomyelitis are among the most serious complications in orthopaedics and traumatology. The risk factors for these infections are often bacterial resistance to antimicrobials. One of the few solutions available to control bacterial resistance involves antimicrobials, which have a different mechanism of action from traditional antibiotics. Antimicrobial peptides (AMP) appear to be highly promising candidates in the treatment of resistant infections. We have identified several AMP in the venom of various wild bees and designed analogues that show potent antimicrobial activity and low toxicity against eukaryotic cells. The aim of the present study was to test the efficacy of one of those synthetic peptide analogues for the treatment of acute osteomyelitis invoked in laboratory rats. Femoral cavities of 20 laboratory Wistar rats were infected with Staphylococcus aureus. After 1 week, eight rats received an injectable calcium phosphate carrier alone, another eight rats were treated with a calcium phosphate mixed with AMP, and four rats were left without any further treatment. After another week, all rats were euthanized and radiographs were made of both the operated and healthy limbs. The animals with the carrier alone exhibited more severe acute osteomyelitis on radiographs in comparison to the recipients of the calcium phosphate carrier loaded AMP and untreated infected individuals. Based on the results of the above mentioned experiment, it was concluded that when injected directly into the site of femoral acute osteomyelitis, the calcium phosphate carrier mixed with AMP reduced osteomyelitis signs visible on radiographs.

摘要

关节置换感染和骨髓炎是骨科和创伤学中最严重的并发症之一。这些感染的危险因素通常是细菌对抗菌药物的耐药性。控制细菌耐药性的少数可用解决方案之一涉及抗菌药物,其作用机制与传统抗生素不同。抗菌肽(AMP)似乎是治疗耐药性感染的极有前景的候选药物。我们在各种野生蜜蜂的毒液中鉴定出了几种抗菌肽,并设计了对真核细胞具有强大抗菌活性和低毒性的类似物。本研究的目的是测试其中一种合成肽类似物治疗实验室大鼠急性骨髓炎的疗效。将20只实验用Wistar大鼠的股骨腔感染金黄色葡萄球菌。1周后,8只大鼠仅接受可注射的磷酸钙载体,另外8只大鼠用与抗菌肽混合的磷酸钙治疗,4只大鼠不进行任何进一步治疗。再过一周后,对所有大鼠实施安乐死,并对手术肢体和健康肢体进行X光摄影。与接受负载抗菌肽的磷酸钙载体的大鼠和未治疗的感染个体相比,仅接受载体的动物在X光片上表现出更严重的急性骨髓炎。基于上述实验结果,得出的结论是,当直接注射到股骨急性骨髓炎部位时,与抗菌肽混合的磷酸钙载体可减少X光片上可见的骨髓炎迹象。

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