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Jae Eun Choi Tyler Werbel Zhenping Wang Chia Chi Wu Tony L. Yaksh Anna Di Nardo 《Journal of dermatological science》2019,93(1):58-64
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13.
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Clinical usefulness of intraductal ultrasonography for the management of acute biliary pancreatitis
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Recent studies have reported an association between gastroesophageal reflux disease (GERD) and atrial fibrillation (AF). The objective of the present study was to evaluate whether AF is one of the risk factors for GERD occurrence.In this hospital-based, retrospective, case–control study, the patients were classified into 2 groups. The patients diagnosed with new AF were assigned to the AF group (n = 1612); those diagnosed without AF and GERD were assigned to the control group (n = 1612). The subjects in the control group were selected from outpatients of total healthcare center without a history of AF or GERD, and matched for age and gender. We evaluated the incidence of GERD and risk factors for GERD occurrence between the 2 groups.The number of patients experiencing occurrence of GERD during the follow-up period was significantly higher in the AF group than those in the control group, respectively (129 patients vs 98 subjects, P = 0.037). The incidence of GERD was significantly higher in the AF group than in the control group by Kaplan–Meier analysis with log-rank test (P = 0.008). The AF group''s adjusted hazard ratio of GERD occurrence against that of the control group was 1.37 (95% confidence interval [CI]: 1.16–1.57; P = 0.009) according to Cox''s proportional hazard model.The presence of AF appears to increase the incidence of GERD and may be considered a risk factor for the development of GERD. Further, large prospective and cohort studies will be required to better establish the correlation of GERD with AF. 相似文献
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The cingulum, connecting the orbitofrontal cortex to the medial temporal lobe, involves in diverse cognition functions including attention, memory, and motivation. To investigate the relationship between the cingulum injury and cognitive impairment in patients with chronic mild traumatic brain injury, we evaluated the integrity between the anterior cingulum and the basal forebrain using diffusion tensor tractography in 73 patients with chronic mild traumatic brain injury(39 males, 34 females, age 43.29 ± 11.42 years) and40 healthy controls(22 males, 18 females, age 40.11 ± 16.81 years). The patients were divided into three subgroups based on the integrity between the anterior cingulum and the basal forebrain on diffusion tensor tractography: subgroup A(n = 19 patients)-both sides of the anterior cingulum were intact; subgroup B(n= 36 patients)-either side of the anterior cingulum was intact; and subgroup C(18 patients)-both sides of the anterior cingulum were discontinued. There were significant differences in total Memory Assessment Scale score between subgroups A and B and between subgroups A and C. There were no significant differences in diffusion tensor tractography parameters(fractional anisotropy, apparent diffusion coefficient, and fiber volume) between patients and controls. These findings suggest that the integrity between the anterior cingulum and the basal forebrain, but not diffusion tensor tractography parameter, can be used to predict the cognitive function of patients with chronic mild traumatic brain injury. This study was approved by Yeungnam University Hospital Institutional Review Board(approval No. YUMC-2014-01-425-010) on August 16, 2017. 相似文献