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局部应用几丁质凝胶-去铁酮-原卟啉镓在绵羊模型中的安全性和有效性

Safety and Efficacy of Topical Chitogel- Deferiprone-Gallium Protoporphyrin in Sheep Model.

作者信息

Ooi Mian L, Richter Katharina, Drilling Amanda J, Thomas Nicky, Prestidge Clive A, James Craig, Moratti Stephen, Vreugde Sarah, Psaltis Alkis J, Wormald Peter-John

机构信息

Department of Surgery- Otolaryngology, Head and Neck Surgery, Basil Hetzel Institute for Translational Health Research, The University of Adelaide, Adelaide, SA, Australia.

Adelaide Biofilm Test Facility, Sansom Institute for Health Research, University of South Australia, Adelaide, SA, Australia.

出版信息

Front Microbiol. 2018 May 11;9:917. doi: 10.3389/fmicb.2018.00917. eCollection 2018.

DOI:10.3389/fmicb.2018.00917
PMID:29867828
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5958210/
Abstract

Increasing antimicrobial resistance has presented new challenges to the treatment of recalcitrant chronic rhinosinusitis fuelling a continuous search for novel antibiofilm agents. This study aimed to assess the safety and efficacy of Chitogel (Chitogel®, Wellington New Zealand) combined with novel antibiofilm agents Deferiprone and Gallium Protoporphyrin (CG-DG) as a topical treatment against biofilms . To assess safety, 8 sheep were divided into two groups of 7 day treatments ( = 8 sinuses per treatment); (1) Chitogel (CG) with twice daily saline flush, and (2) CG-DG gel with twice daily saline flush. Tissue morphology was analyzed using histology and scanning electron microscopy (SEM). To assess efficacy we used a sheep sinusitis model. Fifteen sheep were divided into three groups of 7 day treatments ( = 10 sinuses per treatment); (1) twice daily saline flush (NT), (2) Chitogel (CG) with twice daily saline flush, and (3) CG-DG gel with twice daily saline flush. Biofilm biomass across all groups was compared using LIVE/DEAD BacLight stain and confocal scanning laser microscopy. Safety study showed no cilia denudation on scanning electron microscopy and no change in sinus mucosa histopathology when comparing CG-DG to CG treated sheep. COMSTAT2 assessment of biofilm biomass showed a significant reduction in CG-DG treated sheep compared to NT controls. Results indicate that CG-DG is safe and effective against biofilms in a sheep sinusitis model and could represent a viable treatment option in the clinical setting.

摘要

日益增加的抗菌药物耐药性给顽固性慢性鼻窦炎的治疗带来了新挑战,促使人们不断寻找新型抗生物膜药物。本研究旨在评估壳聚糖凝胶(Chitogel®,新西兰惠灵顿)联合新型抗生物膜药物去铁酮和原卟啉镓(CG-DG)作为局部治疗生物膜的安全性和有效性。为评估安全性,将8只绵羊分为两组,进行为期7天的治疗(每次治疗 = 8个鼻窦);(1)壳聚糖凝胶(CG),每日用生理盐水冲洗两次,以及(2)CG-DG凝胶,每日用生理盐水冲洗两次。使用组织学和扫描电子显微镜(SEM)分析组织形态。为评估有效性,我们使用了绵羊鼻窦炎模型。将15只绵羊分为三组,进行为期7天的治疗(每次治疗 = 10个鼻窦);(1)每日用生理盐水冲洗两次(NT),(2)壳聚糖凝胶(CG),每日用生理盐水冲洗两次,以及(3)CG-DG凝胶,每日用生理盐水冲洗两次。使用LIVE/DEAD BacLight染色和共聚焦扫描激光显微镜比较所有组的生物膜生物量。安全性研究表明,与CG治疗的绵羊相比,CG-DG治疗的绵羊在扫描电子显微镜下未出现纤毛剥脱,鼻窦黏膜组织病理学也无变化。COMSTAT2对生物膜生物量的评估显示,与NT对照组相比,CG-DG治疗的绵羊生物膜生物量显著减少。结果表明,CG-DG在绵羊鼻窦炎模型中对生物膜安全有效,可能是临床环境中一种可行的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4e/5958210/214cdd3f2aed/fmicb-09-00917-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4e/5958210/81ea15a55a9d/fmicb-09-00917-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4e/5958210/e79fc10b70f9/fmicb-09-00917-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4e/5958210/0b85f317f0ce/fmicb-09-00917-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4e/5958210/b0747c1e44bc/fmicb-09-00917-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4e/5958210/558a2d5b1d49/fmicb-09-00917-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4e/5958210/214cdd3f2aed/fmicb-09-00917-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4e/5958210/81ea15a55a9d/fmicb-09-00917-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4e/5958210/e79fc10b70f9/fmicb-09-00917-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4e/5958210/0b85f317f0ce/fmicb-09-00917-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4e/5958210/b0747c1e44bc/fmicb-09-00917-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4e/5958210/558a2d5b1d49/fmicb-09-00917-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4e/5958210/214cdd3f2aed/fmicb-09-00917-g0006.jpg

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Innovative approaches to treat biofilm-related infections.
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