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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   
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4.

Introduction

In the United States there has been a large increase in participation in lacrosse for both males and females. The purpose of this study was to analyze the number of head injuries, injury rates (calculated using the reported number of participants) and types of head injuries that are seen in emergency departments in the United States.

Methods

We compared injuries between male and female lacrosse participants. This was a retrospective study using a publicly available database produced by the US Consumer Product Safety Commission and information about lacrosse participation from US Lacrosse.

Results

A linear regression was performed and showed a positive correlation between number of head injuries to males and time from 2002 to 2010 (R2?=?0.823; p?=?0.001). While the number of injuries to the head in female lacrosse participants was not significant. There was a negative correlation between the number of head injuries to males from 2010 to 2016 (R2?=?0.800; p?=?0.007), but again, there was no significance for female injury count (R2?=?0.417; p?=?0.117). Other significant differences between head injuries in males and females included the mechanism of injury and the type of injury recorded.

Conclusion

The most recent data from 2010 to 2016, suggest that both males and females have had a decrease in injury rate. However the total number of female head injuries is not significantly decreasing and as the sport continues to grow there will likely be more total head injuries and visits to the emergency department.  相似文献   
5.
The numbers of free flap donor site as well as their indications are constantly increasing. Despite increasing popularity of microvascular reconstructive procedures, literature lacks clear and objective outcome criteria. This paper reports on a simple outcome classification that has become a routine part of the unit's large workload of microvascular outcome recording. The classification was formed through a retrospective analysis of 241 consecutive cases from 2000 to 2001 and is a five graded numerical classification. Grade 1 equates to total success without co-morbidity and grade 5 to a major complication such as amputation, etc., whatever the status of the flap itself. From 2002 to 2005 the classification was prospectively used on 527 consecutive cases with ease of integration into routine clinical practice. The Classification would enable a more objective record keeping thus analysis of the outcome. It would allow a more realistic comparison of different techniques or donor types as well set a benchmarking level for further improvement of the results.  相似文献   
6.
Endoscopic clips have been used mainly for control of gastrointestinal (GI) bleeding and occasionally for closure of GI perforations. However, closure of spontaneous esophageal perforation (Boerhaave's syndrome) by clipping has not been reported. We described successful non-surgical closure of spontaneous esophageal perforation by endoscopic clipping in a patient with bilateral pyopneumothorax and septicemia.  相似文献   
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Molecular characterization of Wuchereria bancrofti is essential to develop suitable anti-filarial drugs and vaccines. We describe here isolation, sequence analysis and cloning of a partial cDNA of an enzyme superoxide dismutase from this parasite. The immunoscreening of a lambda zap W. bancrofti microfilarial (Mf) cDNA library with microfilaremic sera had resulted in the isolation of several seroreactive clones including, WbSOD. This clone contained a 309 bp insert and showed significant nucleotide and deduced amino acid sequence homologies to the superoxide dismutases of other nematode parasites. The antioxidant property of this enzyme may have important contribution in the defense mechanism of the parasite against host immune response.  相似文献   
9.
OBJECTIVES: to examine the management and outcome of patients with traumatic popliteal artery pseudoaneurysms with delayed presentation. MATERIALS: over a 2-year period 7 patients with traumatic popliteal pseudoaneurysms presenting to a tertiary referral unit after a delay of 1 month were reviewed. METHODS: a retrospective review of clinical records. RESULTS: the median interval between injury and presentation was 1.5 months (range 1-24 months). Penetrating trauma from gunshot wounds was the cause of the initial vascular injury in 6 patients and a stab wound in one. All patients had large pseudoaneurysms of more than 8 cm filling the popliteal fossa with variable degrees of fixed flexion deformity (FFD) of the knee. Severe FFD of more than 40 degrees was noted in 2 patients and 3 others had mild flexion deformities of 10 to 20 degrees. Six patients underwent repair of the pseudoaneurysm. One patient required an above knee amputation due to an infected false aneurysm. There were no deaths or graft related complications. Despite aggressive post-operative physiotherapy only 2 patients were able to completely straighten the leg at the time of discharge. CONCLUSIONS: in patients with neglected popliteal artery pseudoaneurysms, morbidity is associated with the pre-operative degree of fixed flexion deformity of the knee.  相似文献   
10.
The impact of recombinant human tumour necrosis factor-alpha (1 microgram kg-1 to 1 mg kg-1; 6.6 x 10(6) U mg protein-1) on blood flow, oxygen consumption and growth of a moderately TNF-sensitive rat tumour (DS-carcinosarcoma) was studied. Tumour growth was stimulated at low TNF doses (1 and 10 micrograms kg-1) and significantly retarded at higher TNF dose levels (0.1 and 1 mg kg-1). Growth changes were concomitant with variations in oxygen consumption, lactate release and acidification of the metabolic micromilieu. Both single and repeated application of low TNF doses (1-10 micrograms kg-1 i.v.) increased tumour perfusion whereas single administration of high TNF dose levels (0.1-1 mg kg-1 i.v.) reduced tumour blood flow. After repeated application of high TNF doses tumours shrank to such small sizes that perfusion measurements could not be performed within the observation period of two weeks. It is concluded that TNF effects on solid tumours are at least partially mediated by changes in tumour perfusion. Thus, an altered tumour sensitivity towards other treatment modalities, e.g. irradiation, chemotherapy or hyperthermia, can be expected after TNF therapy. A beneficial TNF effect would critically depend on the dose level employed and on the sequence and timing of various combination regimes.  相似文献   
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