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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   
3.
Abstract

This study is a single-center, retrospective analysis of postmenopausal women presenting with dyspareunia and vulvar pain, aiming to evaluate relative effectiveness of vestibular CO2 laser therapy as a treatment. Three monthly sessions of laser were performed to each patient and thereafter a three-months follow-up was stablished. A total number of 72 patients undergoing vestibular laser treatment were recruited from patient files in the period between 2016 and 2018. Among these, 39 women also received a concomitant treatment with ospemifene (60?mg/day) during the study period. There was a statistically significant reduction of all the symptoms in both groups up to the three month follow-up. Regarding dryness and dyspareunia, the relief tent to be more prominent in the ospemifene?+?laser group at all follow-ups and remained statistically significant at three-month follow-up. Specifically, vestibular dryness was significantly lower in the ospemifene?+?laser group compared with the laser treatment group (?87% vs???34%, respectively), and the vestibular health score started declining faster in the ospemifene?+?laser group. Although, additional research is needed to understand the mechanism of action, our data shows that a combination regimen of laser and ospemifene may improve clinical effectiveness for long-term treatment of symptoms associated with the under-recognized genitourinary syndrome of menopause.  相似文献   
4.
OBJECTIVES: To evaluate a novel method for localization of subdural electrodes in presurgical assessment of patients with drug-resistant focal epilepsy. METHODS: We studied eight consecutive patients with posterior epilepsy in whom subdural electrodes were implanted for presurgical evaluation. Electrodes were detected on post-implantation brain CT scans through a semiautomated procedure based on a MATLAB routine. Then, post-implantation CT scans were fused with pre-implantation MRI to localize the electrodes in relation to the underlying cortical structures. The reliability of this procedure was tested by comparing 3D-rendered MR images of the electrodes with electrode position as determined by intraoperative digital photography. RESULTS: In each patient, all electrodes could be correctly localized and visualized in a stereotactic space, thus allowing optimal surgery planning. The agreement between the procedure-generated images and the digital photographs was good according to two independent raters. The mean mismatch between the 3D images and the photographs was 2 mm. CONCLUSIONS: While our findings need confirmation on larger samples including patients with anterior epilepsy, this procedure allowed to localize subdural electrodes and to establish the spatial relationship of each electrode to the underlying brain structure, either normal or damaged, on brain convessity, basal and medial cortex. SIGNIFICANCE: Being simple, rapid, unexpensive, and reliable, this procedure holds promise to be useful to optimize epilepsy surgery planning.  相似文献   
5.
BACKGROUND/PURPOSE: Sensitive skin is a condition associated with reduced tolerance to environmental factors and/or the application of topical products, such as cosmetics. Its pathophysiology has not been fully elucidated and few data are available on its prevalence. The aim of this study was to investigate possible correlation between objective sensitivity and skin surface microrelief. METHODS: During an epidemiological survey conducted for a campaign promoted by International Society of Plastic Dermatology in Italy, 243 adult healthy subjects of both sexes with no evident dermatological disorder but positive to the lactic acid stinging test, were submitted to cyanoacrylate stratum corneum stripping from the volar forearm for the determination of the irregularity of the skin surface microrelief (irregularity skin index (ISI)). RESULTS: A significant correlation was found between intensity of symptoms in stingers and ISI (r(s)=-0.47; P<0.001). CONCLUSION: Sensitive skin is common in the healthy population. ISI can contribute towards the identification of subjects with sensitive skin and the development of more specific skin treatments for this prevalent condition.  相似文献   
6.
阿格雷(Peter Agre)博士,美国杜克大学医学院细胞生物学系教授,约翰斯霍普金斯大学医学院生物化学系客座教授。阿格雷教授其研究成果在于分离出了长期以来所搜寻的特定输送水分子的通道。这一发现开启了针对细菌、植物和哺乳动物水通道的系列生化、生理和遗传研究之门,从而使得研究人员可以仔细跟踪水分子通过细胞膜的过程,并了解为何只有水分子而不是其他小分子能够通过细胞膜,阿格雷博士也因此获得了2003年诺贝尔化学奖。  相似文献   
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8.
目的:观察体质监测身体功能指标——血压、肺活量/体质量、安静脉搏、台阶指数,了解经济不发达地区女性农民心血管功能现状。方法:于2004-07/08采用随机整群抽样的方法,在湘中地区4个县(市)中随机抽取50~54岁和55~59岁女性农民共400人作为研究对象,用体质测量仪对反映心血管功能的指标进行测定,包括血压、肺活量、安静脉搏、台阶指数。并将所获数据分别与全国同龄女性农民及湖南省城市体力、非体力劳动人群心血管功能指标进行差异性比较。测试同时对测试对象进行询问访谈,内容包括生活环境和经济收入、劳动生活方式、饮食营养习惯、体育锻炼现状、疾病情况等。要求测试者根据自己的实际情况如实回答。结果:400人均完成指标测试,全部进入结果分析。①湘中女性农民50~54岁高血压患病率为31.09%,55~59岁为40.13%,以1级、2级高血压为主。55~59岁年龄组,湘中女性农民收缩压和舒张压均高于全国农民及省内城市人群(P<0.05)。两年龄组比较,55~59岁年龄组高于50~54岁年龄组。②湘中55~59岁女性农民肺活量/体质量低于湖南省城市体力、非体力劳动人群(P<0.01,0.05)。③湘中50~54岁女性农民安静心率高于湖南省城市非体力人群(P<0.01)。④湘中55~59岁女性农民台阶指数低于湖南省城市体力劳动人群(P<0.05)。⑤湘中女性农民的心血管功能受体育锻炼、饮食习惯、经济等因素的影响。结论:湘中地区50~59岁女性农民心血管功能整体低于全国农民和湖南城市体力、非体力人群。影响湘中女性农民身体功能的主要因素有缺乏体育锻炼、饮食习惯、落后经济等因素。  相似文献   
9.
肾移植术后并发尿路上皮肿瘤的临床分析   总被引:8,自引:0,他引:8  
目的 分析肾移植患者并发尿路上皮肿瘤的特点,探讨其诊治方法。方法 自1998~2003年肾移植患者1293例,术后发生尿路上皮恶性肿瘤21例(1.6%)。男4例,女17例。17例原发病为慢性问质性肾炎。发生尿路上皮肿瘤距肾移植6~62个月,平均26个月。其中膀胱癌6例,单侧肾盂或输尿管癌6例,单侧肾盂或输尿管、膀胱癌8例,双侧肾盂输尿管癌1例。10例上尿路肿瘤发生部位与移植肾同侧,4例发生于移植肾对侧。临床症状以无痛性肉服血尿和反复泌尿系感染为主。19例行手术治疗,术后所有患者免疫抑制剂用量减少1/3并辅以局部灌注化疗。结果 2例行姑息性治疗的晚期肿瘤患者分别于发现肿瘤5、8个月死亡。余19例现已随访2~5年。13例肿瘤复发,复发部位为膀胱或对侧原。肾、输尿管。所有患者在免疫抑制剂减量期间均未出现急性排斥。2例因切除移植肾恢复透析,17例肾功能正常。结论 慢性间质性。肾炎导致。肾功能衰竭的。肾移植患者和女性肾移植患者易发生移植后尿路上皮肿瘤;移植肾同侧上尿路较对侧好发肿瘤;对移植肾对侧为首发的上尿路发生肿瘤者可预防性行双侧上尿路根治性切除。  相似文献   
10.
BACKGROUND: In the central nervous system, several neuropeptides are believed to be involved in the pathophysiology of Alzheimer's disease (AD). Indeed, previous studies have documented that glucagon-like peptide 1 (GLP-1) possesses neurotropic properties and can reduce amyloid-beta peptide levels in the brain in vivo. Moreover, the concentrations of neuropeptide Y (NPY) seem to be altered in the cerebrospinal fluid of patients with AD and in subjects with major depression. Finally, among the modifications induced by aging, a dysregulation of the ghrelin-growth hormone (GH) system has been reported. METHODS: We investigated the plasma concentrations of these neuropeptides in 14 subjects with AD. Data obtained from these patients were compared with data from an age- and weight-matched healthy group. RESULTS: No significant differences were found between the two groups in relation to plasma levels of GLP-1, NPY, ghrelin and GH. Peripheral NPY concentrations were positively correlated with ghrelin levels in both groups, and with plasma GLP-1 concentration only in controls. CONCLUSION: On the basis of our results, peripheral levels of these neuropeptides seem not to serve as biochemical markers of AD.  相似文献   
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