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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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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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Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, HSD11B2, cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, defective HSD11B2 enzyme activity results in overstimulation of the mineralocorticoid receptor (MR) by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension. Here, we have studied whether genetic variations in HDS11B2 are implicated in essential hypertension in Japanese hypertensives and the general population. By sequencing the entire coding region and the promoter region of HDS11B2 in 953 Japanese hypertensives, we identified five missense mutations in 11 patients (L14F, n = 5; R74H, n = 1; R147H, n = 3; T156I, n = 1; R335H, n = 1) and one novel frameshift mutation (4884Gdel, n = 1) in a heterozygous state, in addition to 19 genetic variations. All genetic variations identified were rare, with minor allele frequencies less than 0.005. Four of 12 patients with the missense/frameshift mutations showed renal failure. Four missense mutations, L14F, R74H, R147H, and R335H, were successfully genotyped in the general population, with a sample size of 3,655 individuals (2,175 normotensives and 1,480 hypertensives). Mutations L14F, R74H, R147H, and R335H were identified in hypertensives (n = 6, 8, 3, and 0, respectively) and normotensives (n = 8, 12, 5, and 0, respectively) with a similar frequency, suggesting that these missense mutations may not strongly affect the etiology of essential hypertension. Since the allele frequency of all of the genetic variations identified in this study was rare, an association study was not conducted. Taken together, our results indicate that missense mutations in HSD11B2 do not substantially contribute to essential hypertension in Japanese.  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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This paper describes the use of a composite graft from the mastoid area consisting of full-thickness skin peripherally and selectively localised fascia-fat tissue underneath the skin centrally for immediate reconstruction of moderate defects of the nasal tip including the columella and soft triangle. Mastoid composite grafting is a simple and safe procedure that avoids partial graft loss and provides adequate augmentation of soft tissue, easy reshaping of the new nostril rim, minimal post-operative shrinkage, and no donor-site morbidity. Then, it results in a satisfactory nasal appearance with adequate tip projection and symmetry. This procedure may represent a preferred method of nasal tip reconstruction.  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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