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Background

Rosacea is a chronic inflammatory skin condition whose etiology has been linked to mast cells and the antimicrobial peptide cathelicidin LL-37. Individuals with refractory disease have demonstrated clinical benefit with periodic injections of onabotulinum toxin, but the mechanism of action is unknown.

Objectives

To investigate the molecular mechanism by which botulinum toxin improves rosacea lesions.

Methods

Primary human and murine mast cells were pretreated with onabotulinum toxin A or B or control. Mast cell degranulation was evaluated by β-hexosaminidase activity. Expression of botulinum toxin receptor Sv2 was measured by qPCR. The presence of SNAP-25 and VAMP2 was established by immunofluorescence. In vivo rosacea model was established by intradermally injecting LL-37 with or without onabotulinum toxin A pretreatment. Mast cell degranulation was assessed in vivo by histologic counts. Rosacea biomarkers were analyzed by qPCR of mouse skin sections.

Results

Onabotulinum toxin A and B inhibited compound 48/80-induced degranulation of both human and murine mast cells. Expression of Sv2 was established in mouse mast cells. Onabotulinum toxin A and B increased cleaved SNAP-25 and decreased VAMP2 staining in mast cells respectively. In mice, injection of onabotulinum toxin A significantly reduced LL-37-induced skin erythema, mast cell degranulation, and mRNA expression of rosacea biomarkers.

Conclusions

These findings suggest that onabotulinum toxin reduces rosacea-associated skin inflammation by directly inhibiting mast cell degranulation. Periodic applications of onabotulinum toxin may be an effective therapy for refractory rosacea and deserves further study.  相似文献   
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Journal of Neuro-Oncology - Practice patterns vary for adjuvant treatment of 1p/19q-codeleted oligodendroglioma patients. This study evaluates the outcomes of adjuvant (aRT) versus salvage...  相似文献   
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BackgroundThe American Radium Society (ARS) Appropriate Use Criteria brain malignancies panel systematically reviewed (PRISMA [Preferred Reporting Items for Systematic Reviews and Meta-Analyses]) published literature on neurocognitive outcomes after stereotactic radiosurgery (SRS) for patients with multiple brain metastases (BM) to generate consensus guidelines.MethodsThe panel developed 4 key questions (KQs) to guide systematic review. From 11 614 original articles, 12 were selected. The panel developed model cases addressing KQs and potentially controversial scenarios not addressed in the systematic review (which might inform future ARS projects). Based upon quality of evidence, the panel confidentially voted on treatment options using a 9-point scale of appropriateness.ResultsThe panel agreed that SRS alone is usually appropriate for those with good performance status and 2–10 asymptomatic BM, and usually not appropriate for >20 BM. For 11–15 and 16–20 BM there was (between 2 case variants) agreement that SRS alone may be appropriate or disagreement on the appropriateness of SRS alone. There was no scenario (among 6 case variants) in which conventional whole-brain radiotherapy (WBRT) was considered usually appropriate by most panelists. There were several areas of disagreement, including: hippocampal sparing WBRT for 2–4 asymptomatic BM; WBRT for resected BM amenable to SRS; fractionated versus single-fraction SRS for resected BM, larger targets, and/or brainstem metastases; optimal treatment (WBRT, hippocampal sparing WBRT, SRS alone to all or select lesions) for patients with progressive extracranial disease, poor performance status, and no systemic options.ConclusionsFor patients with 2–10 BM, SRS alone is an appropriate treatment option for well-selected patients with good performance status. Future study is needed for those scenarios in which there was disagreement among panelists.  相似文献   
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