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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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目的分析托珠单抗的安全性风险,为临床合理用药提供参考。方法对世界卫生组织药品不良反应监测数据库、我国药品不良反应监测数据库、国内文献数据库中的不良反应报告情况及国外药监机构风险控制措施等相关资料进行整理与分析。结果应重视托珠单抗临床使用中可能发生的肝功能异常、皮肤损害、过敏反应、胃肠道损害、感染、血液系统损害等不良反应。结论托珠单抗临床使用中,应加强对严重感染及肝功能损害等严重不良反应的安全性监测,促进药品的临床合理使用。  相似文献   
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全国名中医天津中医药大学第一附属医院针灸科武连仲教授用多年的临床经验总结概括出针刺的理、法、方、穴、术,其创立的"通经止痛"针刺疗法在临床中疗效佳,武老在治疗坐骨神经痛时,取足太阳膀胱经和足少阳胆经具有走窜针感的经穴为主穴,其配伍精确,组方严密,手法独特,可供临床参考。本文将武老运用"痛经止痛"针刺法治疗坐骨神经痛的经验从"理、法、方、穴、术"方面做浅述。  相似文献   
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石颖  吴玲  李林苇 《中国临床康复》2006,10(48):151-153
目的:综述运动系统软组织损伤引起慢性疼痛的各种治疗方法的研究进展。资料来源:应用计算机检索Medline1980—01/2006—04与运动系统软组织损伤引起慢性疼痛的治疗相关文章,检索词“Soft tissue injury,pain.chronic,comprehensive therapy”,并限定文章语言种类为“English”;同时计算机检索中国期刊全文数据库1994—01/2006-04期间的相关文章,检索词“软组织损伤、慢性疼痛、治疗方法”,并限定语言种类为中文。同时手工查阅相关书籍。资料选择:对资料进行初审,所选文献内容符合:①软组织损伤引起的慢性疼痛药物治疗的研究。②软组织损伤引起的慢性疼痛微创治疗的研究。③软组织损伤引起的慢性疼痛运动疗法的研究。④软组织损伤引起的慢性疼痛心理治疗的研究。⑤软组织损伤引起的慢性疼痛其他疗法的研究。排除重复性研究的文献。资料提炼:共收集到40篇关于软组织损伤引起的慢性疼痛治疗方法的文献,均为全文,23篇符合纳入标准,排除17篇重复性研究。同时录入书籍3本。资料综合:软组织损伤引起的慢性疼痛的产生是生理、心理及社会因素复杂结合的结果,个体表现差异较大,目前尚无特效治疗方法,常用的治疗方法有:药物治疗、微创治疗、运动疗法、心理治疗、物理疗法及其他疗法。结论:对于软组织损伤引起的慢性疼痛的治疗必须以整体的观点对其进行合理的评估和个体化治疗,才能收到良好的效果。  相似文献   
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Objective To investigate effect of reduced glutathione and diammonium glycyrrhizinate on the treatment of hepatic damage in experimental dogs following open abdominal injuries coupled with seawater immersion. Methods Twenty-four dogs with open abdominal injuries were randomly divided into 3 groups: the control group (given with simple observation after 1.5 h seawater immersion); the routine treatment group (given routine care and fluid transfusion after 1.5 h seawater immersion) ; the hepatic treatment group (given routine are, fluid transfusion and hepatic treatment as well, after 1.5 h seawater immersion). Each group consisted of 8 dogs. Blood samples were taken at different time points to measure total bilirubin (TB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), prothromin time (PT), endotoxin, tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), and pathological examination was also made at the same time. Results For the control group, contents of TB, ALT, AST and LDH increased significantly and survival time was less than 24 hours. Contents of TB, ALT, AST and LDH of the routine treatment group also increased significantly, but survival time of all the experimental animals was mere than 24 hours. Reduced glutathione and diammonium glycyrrhizinate could reduce the extent of lesion quite significantly 12~24 hours following open abdominal injuries. Conclusions Reduced glutathione and diammonium glycyrrhizinate seemed to have good effects on the treatment and prevention against hepatic damage induced by trauma coupled with seawater immersion. It could be used as a primary means for the treatment of such kind of hepatic damage.  相似文献   
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Signaling of RANK (receptor activator of nuclear factor kappa B) through its ligand RANKL appears critical in osteolysis associated with aseptic loosening (AL). The purpose of this study was to investigate the role of RANK in a murine osteolysis model developed in RANK knockout (RANK(-/-)) mice. Ultra high molecular weight polyethylene (UHMWPE) debris was introduced into established air pouches on RANK(-/-) mice, followed by implantation of calvaria bone from syngeneic littermates. Wild type C57BL/6 (RANK(+/+)) mice injected with either UHMWPE or saline alone were included in this study. Pouch tissues were collected 14 days after UHMWPE inoculation for molecular and histology analysis. Results showed that UHMWPE stimulation induced strong pouch tissue inflammation in RANK(-/-) mice, as manifested by inflammatory cellular infiltration, pouch tissue proliferation, and increased gene expression of IL-1beta, TNFalpha, and RANKL. However, the UHMWPE-induced inflammation in RANK(-/-) mice was not associated with the osteoclastic bone resorption observed in RANK(+/+) mice. In RANK(+/+) mice subjected to UHMWPE stimulation, a large number of TRAP(+) cells were found on the implanted bone surface, where active osteoclastic bone resorption was observed. No TRAP(+) cells were found in UHMWPE-containing pouch tissues of RANK(-/-) mice. Consistent with the lack of osteoclastic activity shown by TRAP staining, no significant UHMWPE particle-induced bone resorption was found in RANK(-/-) mice. A well preserved bone collagen content (Van Gieson staining) and normal plateau surface contour [microcomputed tomography (microCT)] of implanted bone was observed in RANK(-/-) mice subjected to UHMWPE stimulation. In conclusion, this study provides the evidence that UHMWPE particles induce strong inflammatory responses, but not associated with osteoclastic bone resorption in RANK(-/-) mice. This indicates that RANK signaling is essential for UHMWPE particle-induced osteoclastic bone resorption, but does not participate in UHMWPE particle-induced inflammatory response.  相似文献   
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目的:综合分析近年来国内外神经修复用导管材料以及制备方法的研究近况。资料来源:应用计算机检索ElsevierScience1996-01/2005-12有关神经修复及神经导管方面的文献,检索词分别为“nerveconduit,nerveguide,nerveregeneration”,限定文献语言种类为English。同时计算机检索清华数字期刊库、万方数据库1996-01/2005-12有关神经修复及神经导管方面的文献,检索词为“神经修复,导管”,限定语言种类为中文。资料选择:对检索到的神经再生、神经修复及神经导管方面的相关信息进行整理,选取针对性强的文章。同一领域的文献则选择近期发表或权威杂志的文章。资料提炼:共收集120篇关于神经修复、神经导管的文献,纳入23篇符合标准的文献。资料综合:用神经导管桥接断离神经是神经修复的重要方法之一,制备神经导管的材料按其降解性能分为生物不可降解材料和生物可降解材料,任何一种材料都有其优缺点,发展复合材料将是制备导管的主要方向。结论:虽然影响神经再生的因素还有许多,如神经生长因子、雪旺细胞等,但是新型的导管及制备方法将会有利于神经修复进一步发展。  相似文献   
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