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常见溶剂在小鼠烧伤部位感染模型中对抗铜绿假单胞菌诱导的致病性的作用。

The Role of Common Solvents against Pseudomonas aeruginosa-Induced Pathogenicity in a Murine Burn Site Infection Model.

机构信息

Department of Surgery, Harvard Medical School and Massachusetts General Hospitalgrid.32224.35, Boston, Massachusetts, USA.

Shriners Hospitals for Children Boston, Boston, Massachusetts, USA.

出版信息

Microbiol Spectr. 2021 Sep 3;9(1):e0023321. doi: 10.1128/Spectrum.00233-21. Epub 2021 Aug 4.

DOI:10.1128/Spectrum.00233-21
PMID:34346751
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8552656/
Abstract

Dimethyl sulfoxide (DMSO) and polyethylene glycols (PEGs) are frequently used as potent excipients in pharmaceutical formulations. However, these agents also have an interesting antimicrobial and anti-inflammatory profile that could interfere with the efficacy testing of anti-infective compounds when the latter are solubilized in DMSO or PEGs. Here, we demonstrate the antimicrobial and anti-inflammatory effects of DMSO-PEG400 in a murine Pseudomonas aeruginosa infection model, aiming to draw attention to the appropriate selection of solvents for difficult-to-solubilize anti-infectives. Our study demonstrates the antimicrobial and anti-inflammatory effects of the combination of DMSO and PEG400 against Pseudomonas aeruginosa and in a murine infection model of heightened intestinal permeability. The aim of this study is to draw attention to the appropriate selection of solvents for difficult-to-solubilize anti-infective compounds, to avoid interference with the assay or system tested. This is an extremely important consideration, since potential antimicrobial and anti-inflammatory effects of the solvent vehicle are detrimental to research studies on the efficacy of new anti-infective agents, given that the vehicle effect can mask the effect of the tested compounds. Our results can therefore be of great value to the scientific community, as they can guide researchers in the future to avoid this significant pitfall that can cost substantial amounts of money and valuable time during investigations of the effects of novel, difficult-to-solubilize antimicrobial compounds.

摘要

二甲基亚砜(DMSO)和聚乙二醇(PEG)经常被用作药物制剂中的有效赋形剂。然而,这些试剂也具有有趣的抗菌和抗炎特性,如果将抗感染化合物溶解在 DMSO 或 PEG 中,可能会干扰其疗效测试。在这里,我们在铜绿假单胞菌感染模型中证明了 DMSO-PEG400 的抗菌和抗炎作用,旨在引起人们对难以溶解的抗感染药物选择合适溶剂的关注。

我们的研究表明,DMSO 和 PEG400 的组合对铜绿假单胞菌具有抗菌和抗炎作用,并且在肠道通透性增加的小鼠感染模型中也具有这种作用。本研究的目的是引起人们对难以溶解的抗感染化合物的溶剂选择的关注,以避免对测定或测试系统产生干扰。这是一个极其重要的考虑因素,因为溶剂载体的潜在抗菌和抗炎作用会损害新抗感染药物疗效的研究,因为载体效应会掩盖测试化合物的作用。因此,我们的研究结果对于科学界具有重要价值,因为它们可以指导未来的研究人员避免这种重大陷阱,这可能会在研究新型、难以溶解的抗菌化合物的效果时花费大量的金钱和宝贵的时间。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea6/8552656/ad03eae93c6a/spectrum.00233-21-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea6/8552656/2d0fe90e0efb/spectrum.00233-21-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea6/8552656/2d80ebeb3806/spectrum.00233-21-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea6/8552656/53b1b78b7cd3/spectrum.00233-21-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea6/8552656/ad03eae93c6a/spectrum.00233-21-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea6/8552656/2d0fe90e0efb/spectrum.00233-21-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea6/8552656/2d80ebeb3806/spectrum.00233-21-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea6/8552656/53b1b78b7cd3/spectrum.00233-21-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ea6/8552656/ad03eae93c6a/spectrum.00233-21-f004.jpg

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本文引用的文献

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Adverse reactions of dimethyl sulfoxide in humans: a systematic review.二甲基亚砜在人体中的不良反应:一项系统评价。
F1000Res. 2018 Nov 5;7:1746. doi: 10.12688/f1000research.16642.2. eCollection 2018.
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Targeting bacterial quorum sensing shows promise in improving intestinal barrier function following burn‑site infection.靶向细菌群体感应有望改善烧伤部位感染后的肠道屏障功能。
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Low dose dimethyl sulfoxide driven gross molecular changes have the potential to interfere with various cellular processes.
低剂量二甲基亚砜驱动的总分子变化有可能干扰各种细胞过程。
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Dimethyl Sulfoxide (DMSO) Decreases Cell Proliferation and TNF-α, IFN-γ, and IL-2 Cytokines Production in Cultures of Peripheral Blood Lymphocytes.二甲基亚砜(DMSO)降低外周血淋巴细胞培养物中的细胞增殖和 TNF-α、IFN-γ 和 IL-2 细胞因子的产生。
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Pharmacological Inhibition of the Pseudomonas aeruginosa MvfR Quorum-Sensing System Interferes with Biofilm Formation and Potentiates Antibiotic-Mediated Biofilm Disruption.抑制铜绿假单胞菌 MvfR 群体感应系统的药理学干预会干扰生物膜的形成,并增强抗生素介导的生物膜破坏。
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