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局部皮质类固醇和利多卡因对鼠皮肤中伯氏疏螺旋体的影响:对人体临床试验的潜在影响。

Effects of topical corticosteroids and lidocaine on Borrelia burgdorferi sensu lato in mouse skin: potential impact to human clinical trials.

机构信息

Fédération de Médecine Translationnelle - UR7290, Virulence bactérienne précoce-groupe Borrelia, Université de Strasbourg, 67000, Strasbourg, France.

Laboratoire de Spectrométrie de Masse BioOrganique, CNRS, IPHC UMR 7178, Université de Strasbourg, 67000, Strasbourg, France.

出版信息

Sci Rep. 2020 Jun 29;10(1):10552. doi: 10.1038/s41598-020-67440-5.

Abstract

Lyme borreliosis is the most prevalent vector-borne disease in northern hemisphere. Borrelia burgdorferi sensu lato spirochetes are transmitted by Ixodes species ticks. During a blood meal, these spirochetes are inoculated into the skin where they multiply and often spread to various target organs: disseminated skin sites, the central nervous system, the heart and large joints. The usual diagnosis of this disease relies on serological tests. However, in patients presenting persistent clinical manifestations, this indirect diagnosis is not capable of detecting an active infection. If the serological tests are positive, it only proves that exposure of an individual to Lyme spirochetes had occurred. Although culture and quantitative PCR detect active infection, currently used tests are not sensitive enough for wide-ranging applications. Animal models have shown that B. burgdorferi persists in the skin. We present here our targeted proteomics results using infected mouse skin biopsies that facilitate detection of this pathogen. We have employed several novel approaches in this study. First, the effect of lidocaine, a local anesthetic used for human skin biopsy, on B. burgdorferi presence was measured. We further determined the impact of topical corticosteroids to reactivate Borrelia locally in the skin. This local immunosuppressive compound helps follow-up detection of spirochetes by proteomic analysis of Borrelia present in the skin. This approach could be developed as a novel diagnostic test for active Lyme borreliosis in patients presenting disseminated persistent infection. Although our results using topical corticosteroids in mice are highly promising for recovery of spirochetes, further optimization will be needed to translate this strategy for diagnosis of Lyme disease in patients.

摘要

莱姆病是北半球最常见的虫媒传染病。伯氏疏螺旋体属螺旋体通过硬蜱属的蜱传播。在吸血时,这些螺旋体被接种到皮肤中,在那里它们繁殖并经常传播到各种靶器官:弥漫性皮肤部位、中枢神经系统、心脏和大关节。这种疾病的通常诊断依赖于血清学检测。然而,对于出现持续临床症状的患者,这种间接诊断无法检测到活动性感染。如果血清学检测呈阳性,仅证明个体已经接触过莱姆螺旋体。尽管培养和定量 PCR 可检测到活动性感染,但目前使用的检测方法不够灵敏,无法广泛应用。动物模型表明,伯氏疏螺旋体在皮肤中持续存在。我们在这里展示了使用感染小鼠皮肤活检的靶向蛋白质组学结果,这些结果有助于检测这种病原体。在这项研究中,我们采用了几种新方法。首先,测量了局部麻醉剂利多卡因对伯氏疏螺旋体存在的影响。我们进一步确定了局部皮质类固醇对局部重新激活 Borrelia 的影响。这种局部免疫抑制化合物有助于通过对皮肤中存在的 Borrelia 进行蛋白质组分析来跟踪检测螺旋体。这种方法可以作为一种新的诊断测试,用于检测出现弥漫性持续性感染的患者中的活动性莱姆病。尽管我们在小鼠中使用局部皮质类固醇的结果对恢复螺旋体非常有希望,但需要进一步优化才能将这种策略转化为患者莱姆病的诊断。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3490/7324597/225a314c9fc7/41598_2020_67440_Fig1_HTML.jpg

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