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1.

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   
2.
Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) of the human motor cortex produce a silent period (SP) following motor evoked potentials (MEPs). The early part of the SP can be explained by decreased alpha motor neuron excitability, whereas the late part is presumably due to suprasegmental mechanisms. In order to determine the level of the suprasegmental contribution to the generation of SPs, we recorded excitatory and inhibitory responses to TMS, TES, and percutaneous electrical brainstem stimulation (PBS) in the voluntarily activated first dorsal interosseous muscle of the hand. Stimulus intensities were set so that PBS and TES induced MEPs with areas equal to or larger than those of MEPs obtained with TMS. This procedure revealed that SPs were 49% and 83% shorter with TES and PBS, respectively, than with TMS. As TMS is more effective than TES or PBS in activating cortical interneurons, these findings support the idea that a significant component of the SP arises from intracortical mechanisms.  相似文献   
3.
Multimodality evoked potentials and early prognosis in comatose patients   总被引:1,自引:0,他引:1  
In 112 comatose patients somatosensory, visual and auditory evoked potentials were registered within 36 hours after the onset of coma or admission. Main causes of coma were head injury, and intracerebral and subarachnoid haemorrhage. The initial bilateral loss of any evoked potential was associated with a mortality of 98%. Normal somatosensory evoked potentials were associated with a survival rate of 74%, while normal visual and normal auditory evoked potentials had a survival rate of 60% and 66%, respectively. It is concluded that SEPs can be valuable for the prognosis of coma after primary brain lesions.  相似文献   
4.
1. Postmortem neurochemical investigations revealed interhemispheric asymmetry in the mediofrontal region of human brain. Significantly higher right hemisphere serotonin metabolite (5HIAA) content as well as increased maximal imipramine binding (IB) were found in the right hemisphere than in the left side.

2. IB did not show a gender difference in the mediofrontal area. However, women had higher IB in the right orbital frontal cortex than did men.

3. In vivo pharmaco-EEG results tend to support the postmortem neurochemical data. Intravenous chlorimipramine resulted in an asymmetric topographic distribution of the P300 auditory evoked potential, peak amplitudes were shifted to the right hemisphere.  相似文献   

5.
目的 评价控制性降压是否增加脊髓对牵拉损伤的易感性。材料与方法健康成年杂种犬6只,随机分为常压和控制性降压脊髓牵拉损伤组。观察常压及控制性降压水平下相同程度牵拉损伤后脊髓血流(SCBF)、体感诱发电位(SEP)、神经源性运动诱发电位(NMEP)改变的差异。结果 外周血有创动脉压(MABP)平均下降幅度为40.5%。经SSPS统计软件独立样本t检验,不同牵拉水平下,常压组及低压组的SCBF(%)、SEP波幅(Asep)(%)及NMEP波幅(%)无显著差异。结论 尼卡地平控制性降压不增加脊髓对牵拉损伤的易感性。  相似文献   
6.
Electrical stimulation of the phrenic nerve afferents evoked excitatory responses in the right inferior cardiac sympathetic nerve in chloralose-anaesthetized cats. The reflex was recorded in intact and spinal cats. The latency and threshold of the volley recorded from the phrenic nerve as well as of the cord dorsum potentials evoked by electrical stimulation of the phrenic nerve indicated that group III afferents were responsible for this reflex. The phrenicocardiac sympathetic reflex recorded in intact cats was followed by a silent period. The maximum amplitude of the reflex discharges was 800 microV, the latency was 83 ms and the central transmission time 53 ms. Duration of the silent period lasted up to 0.83 s. In spinal cats the reflex was recorded 5.5-8 h after spinalization. The maximum amplitude of the spinal reflex discharges ranged from 22 to 91 microV and the latency from 36 to 66 ms.  相似文献   
7.
8.
Abstract The aim was to measure the effect of gastric electrical stimulation on the frequency of canine antral pacesetter potentials (PPs), the strength of antral contractions, and the rate of gastric emptying while fasting, after feeding and with pentagastrin stimulation. Four conscious dogs with a stimulating electrode placed 10 cm proximal to the pylorus and recording electrodes and strain gauges placed 7, 5 and 3 cm proximal to the pylorus underwent myoelectric and strain gauge recordings while fasting, after feeding (250 ml 5% dextrose labelled with polyethylene glycol), and during pentagastrin infusion (0.5 μg kg?1 min?1) on four separate days. On each day, electrical stimulation was done using one of four stimulation frequencies (0, 6, 30 and 1200 stimuli per minute ***[s.p.m.]). Stimulation at 6 and 30 s.p.m. increased the fasting and fed PP frequency, whereas 1200 s.p.m. stimulation did not. Feeding decreased the maximum driven frequency, and pentagastrin increased it. Neither the motility index nor the gastric emptying rate were consistently changed by stimulation at any frequency. In conclusion, canine proximal antral stimulation at 6 and 30 s.p.m. sped PP frequency during fasting and after feeding, but stimulation over a wide range of frequencies had little effect on gastric contractions and emptying.  相似文献   
9.
Movement-related potentials were recorded preceding self-paced voluntary movements in patients with Parkinson's disease and in healthy subjects of the same age group. We compared the Readiness Potential preceding joystick movements in a fixed direction and preceding joystick movements in freely selected directions. In normal subjects the Readiness Potential amplitude was higher preceding freely selected movements than preceding movements in a fixed direction. The Readiness Potential in Parkinson patients failed to be modified by the different modes of movement selection. The modulation of the Readiness Potential by different ways of preparing for movement might be due to the supplementary motor area (SMA) being more strongly engaged by tasks requiring internal control of movements than by tasks that are externally structured. The results suggest that this task-dependent variation of SMA activity is reduced in Parkinson's disease. A failing capacity to adapt SMA activity to different task demands has previously been suggested by evidence from positron emission tomography studies using similar tasks.  相似文献   
10.
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