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前列地尔血管扩张剂能否预防糖尿病患者的骨科植入物相关感染?小鼠模型的初步结果。

Does PGE₁ vasodilator prevent orthopaedic implant-related infection in diabetes? Preliminary results in a mouse model.

作者信息

Lovati Arianna B, Romanò Carlo L, Monti Lorenzo, Vassena Christian, Previdi Sara, Drago Lorenzo

机构信息

Cell and Tissue Engineering Laboratory, IRCCS Galeazzi Orthopaedic Institute, Milan, Italy.

Dipartimento di Chirurgia Ricostruttiva e delle Infezioni Osteo-articolari, IRCCS Galeazzi Orthopaedic Institute, Milan, Italy.

出版信息

PLoS One. 2014 Apr 9;9(4):e94758. doi: 10.1371/journal.pone.0094758. eCollection 2014.

Abstract

BACKGROUND

Implant-related infections are characterized by bacterial colonization and biofilm formation on the prosthesis. Diabetes represents one of the risk factors that increase the chances of prosthetic infections because of related severe peripheral vascular disease. Vasodilatation can be a therapeutic option to overcome diabetic vascular damages and increase the local blood supply. In this study, the effect of a PGE₁ vasodilator on the incidence of surgical infections in diabetic mice was investigated.

METHODOLOGY

A S. aureus implant-related infection was induced in femurs of diabetic mice, then differently treated with a third generation cephalosporin alone or associated with a PGE₁ vasodilator. Variations in mouse body weight were evaluated as index of animal welfare. The femurs were harvested after 28 days and underwent both qualitative and quantitative analysis as micro-CT, histological and microbiological analyses.

RESULTS

The analysis performed in this study demonstrated the increased host response to implant-related infection in diabetic mice treated with the combination of a PGE₁ and antibiotic. In this group, restrained signs of infections were identified by micro-CT and histological analysis. On the other hand, the diabetic mice treated with the antibiotic alone showed a severe infection and inability to successfully respond to the standard antimicrobial treatment.

CONCLUSIONS

The present study revealed interesting preliminary results in the use of a drug combination of antibiotic and vasodilator to prevent implant-related Staphylococcus aureus infections in a diabetic mouse model.

摘要

背景

植入物相关感染的特征是细菌在假体上定植并形成生物膜。糖尿病是因相关严重外周血管疾病而增加假体感染几率的危险因素之一。血管舒张可能是克服糖尿病血管损伤并增加局部血液供应的一种治疗选择。在本研究中,研究了一种前列腺素E₁血管舒张剂对糖尿病小鼠手术感染发生率的影响。

方法

在糖尿病小鼠的股骨中诱导金黄色葡萄球菌植入物相关感染,然后分别单独用第三代头孢菌素或与前列腺素E₁血管舒张剂联合治疗。将小鼠体重变化作为动物健康指标进行评估。28天后取出股骨,进行微计算机断层扫描(micro-CT)、组织学和微生物学分析等定性和定量分析。

结果

本研究进行的分析表明,在接受前列腺素E₁和抗生素联合治疗的糖尿病小鼠中,宿主对植入物相关感染的反应增强。在该组中,通过微计算机断层扫描和组织学分析确定感染迹象得到抑制。另一方面,单独接受抗生素治疗的糖尿病小鼠表现出严重感染且无法成功应对标准抗菌治疗。

结论

本研究揭示了在糖尿病小鼠模型中使用抗生素和血管舒张剂的药物组合预防植入物相关金黄色葡萄球菌感染方面有趣的初步结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d864/3981866/81a9dd67f59d/pone.0094758.g001.jpg

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