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21.

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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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   
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目的 初步探讨应用艾尔巴韦/格拉瑞韦治疗慢性丙型肝炎(CHC)患者的疗效。方法 2017年3月~2018年3月仙桃市第一人民医院感染病科收治的CHC患者82例,被随机分为对照组41例和观察组41例,分别给予聚乙二醇干扰素-α联合利巴韦林治疗和艾尔巴韦/格拉瑞韦治疗,两组均连续治疗24周。采用RT- PCR法检测血清 HCV RNA,采用全基因序列测定法行病毒基因分型。比较两组早期病毒学应答(EVR)、治疗结束时病毒学应答(ETVR)和持续病毒学应答(SVR)。结果 在治疗结束时,观察组血清丙氨酸氨基转移酶(ALT)水平为(47.9±19.7)U/L,显著低于对照组【(63.5±21.2)U/L,P<0.05】,天冬氨酸氨基转移酶(AST)水平为(55.5±22.3)U/L,显著低于对照组【(81.3±25.8)U/L,P<0.05】;观察组EVR、ETVR和SVR分别为48.8%、63.4%和70.7%,与对照组的41.5%、53.7%和65.8%比,无统计学差异(P>0.05);18例观察组非HCV Ⅰ型感染者EVR、ETVR和SVR分别为88.9%、94.4%和88.9%,显著高于同组23例HCV Ⅰ型感染者(分别为52.2%、60.9%和52.2%, P<0.05),而与对照组15例非HCV Ⅰ型感染者比,无统计学差异(分别为86.7%、93.3%和73.3%, P>0.05);观察组SVR12为87.8%(36/41),显著高于对照组的73.2%(30/41,P<0.05)。结论 应用直接抗病毒(DAA)药物艾尔巴韦/格拉瑞韦治疗CHC患者近期疗效达到,但远期疗效似优于标准治疗方案, 值得临床进一步验证。  相似文献   
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The purpose of the work was to set‐up a simple method to evaluate the contribution of Mn2+ ions in the intra‐ and extracellular tumor compartments in a MEMRI experiment. This task has been tackled by “silencing” the relaxation enhancement arising from Mn2+ ions in the extracellular space. In vitro relaxometric measurements allowed assessment of the sequestering activity of DO2A (1,4,7,10‐tetraazacyclododecane‐1,7‐diacetic acid) towards Mn2+ ions, as the addition of Ca‐DO2A to a solution of MnCl2 causes a drop of relaxivity upon the formation of the highly stable and low‐relaxivity Mn‐DO2A. It has been proved that the sequestering ability of DO2A towards Mn2+ ions is also fully effective in the presence of serum albumin. Moreover, it has been shown that Mn‐DO2A does not enter cell membranes, nor does the presence of Ca‐DO2A in the extracellular space prompt migration of Mn ions from the intracellular compartment. On this basis the in vivo, instantaneous, drop in SE% (percent signal enhancement) in T1‐weighted images is taken as evidence of the sequestration of extracellular Mn2+ ions upon addition of Ca‐DO2A. By applying the method to B16F10 tumor bearing mice, T1 decrease is readily detected in the tumor region, whereas a negligible change in SE% is observed in kidneys, liver and muscle. The relaxometric MRI results have been validated by ICP‐MS measurements. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   
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Over the years, the number of total hip replacements has been steadily increasing. Despite the improvement in surgical results, the number of claims for malpractice is higher. The primary endpoint of this work is to provide an analysis of litigation after hip replacement, to outline what are the instigating causes and costs. The secondary endpoint is to propose a possible preventive strategy for an improved care and a reduction in legal proceedings. The data of this study were collected from medical and legal files and from professional liability insurance of our institution from January 2005 to December 2016. Out of a total of 4770 THA, 40 claims were received. Peripheral nerve injuries represent the first cause of litigation (37%), followed by infectious complications, leg length discrepancy, metallosis, dislocations of the implant and a case of deep vein thrombosis. From the analysis of the past trial judgment, complications such as nerve lesions and infections are almost always recognized, as a medical error, with a high percentage of claims settled. This study shows the necessity of preventive strategies to reduce the higher number of claims for malpractice in total hip arthroplasty. Some complications such as nerve injuries and infection are frequently considered directly dependent on physician’s errors. Litigations can be reduced providing evidence of a diligent execution of the surgical procedure and of a proper postoperative management: the correct compilation of a specific informed consent and adequate doctor–patient communication.  相似文献   
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