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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.
This study evaluated the effect of new motions of the motor TriAuto ZX2 on the cyclic fatigue of endodontic instruments. Vortex Blue 35.06 instruments were divided into four groups (n = 10) and tested for fatigue in a curved artificial canal (90° and 2 mm radius) using the following motions: continuous rotation (CR), Optimum Torque Reverse (OTR) set at 180° and the Optimum Glide Path (OGP), which was tested at 90° and 240°. The time to fracture (TTF) and the lengths of the fractured fragments were recorded. The mean TTF was significantly different among the groups (anova , P < 0.05): OGP 90° (213.39 ± 27.45), OTR 180° (121.24 ± 17.03), OGP 240° (45.24 ± 5.61) and CR (8.43 ± 1.27). Weibull analysis confirmed the shortest life expectancy for CR and the longest survival for OGP at 90°. The resistance to fatigue was affected by motions and pre‐set angles. The proprietary movements that are currently available for endodontic instruments were classified according to their kinematics.  相似文献   
3.
4.
The epsilon-sarcoglycan gene (SGCE) on human chromosome 7q21 has been reported to be a major locus for inherited myoclonus-dystonia. Linkage to the SGCE locus has been detected in the majority of families tested, and mutations in the coding region have been found recently in families with autosomal dominant myoclonus-dystonia. To evaluate the relevance of SGCE in myoclonus-dystonia, we sequenced the entire coding region of the epsilon-sarcoglycan gene in 16 patients with either sporadic or familial myoclonus-dystonia. No mutations were found. This study suggests that epsilon-sarcoglycan does not play an important role in sporadic myoclonus-dystonia and supports genetic heterogeneity in familial cases.  相似文献   
5.
The safety of awake tracheal intubation in cervical spine injury   总被引:4,自引:0,他引:4  
As a referral centre for cervical spine injuries, we have routinely performed awake tracheal intubation when intubation was indicated. A retrospective case control study was undertaken to review the frequency of neurological deterioration and aspiration associated with our approach. Neurological deterioration was assessed by a change in level of injury or neurological grade at admission and discharge. Four hundred and fifty-four patients with critical cervical spine and/or cord injuries were reviewed over an eight-year period. A case group of 165 patients underwent tracheal intubation awake within two months of injury. A control group of 289 remained unintubated during the same period. A comparison of spinal neurological status between admission and discharge revealed no statistically significant difference in neurological deterioration between the two groups. This occurred despite a greater injury severity score in the case group. No evidence of aspiration during intubation was documented. We conclude that awake tracheal intubation is a safe method of airway management in patients with cervical spine injuries.  相似文献   
6.
7.
Background: The differential tolerability profile of various interferon (IFN)-α preparations used in combination with ribavirin for the treatment of chronic hepatitis C needs to be elucidated. Approximately 8% of patients receiving recombinant IFNα-2b plus ribavirin discontinue treatment because of adverse events. Human leucocyte IFNα is deemed to have a better safety profile than recombinant IFNα. We therefore compared the safety profile and efficacy of ribavirin combined with leucocyte IFNα or with recombinant IFNα-2b in treatment-naive patients with chronic hepatitis C. Study design: We randomised 423 patients to either leucocyte IFNα 3MU three times weekly plus ribavirin (210 patients) or the same dose of recombinant IFNα-2b plus ribavirin (213 patients). Patients were treated for 24 weeks and followed-up for a further 48 weeks. The primary endpoint was the safety profile of the two therapies; the secondary endpoint was the rate of sustained response. Results: In patients receiving leucocyte IFNα, the total number of adverse events was lower than in the group receiving recombinant IFNα (259 vs 441 patients), and the percentage of patients discontinuing treatment because of adverse events or laboratory abnormalities was significantly reduced (4% vs 11%; p = 0.013). Sustained response was observed in 47% of patients receiving leucocyte IFNα plus ribavirin and in 44% of patients receiving IFNα-2b plus ribavirin. Conclusions: Both therapeutic regimens were effective in inducing a sustained response in naive patients. However, the safety profile of leucocyte IFNα plus ribavirin was more favourable than that observed with the administration of recombinant IFNα-2b plus ribavirin, suggesting that leucocyte IFNα may be an alternative option in patients with reduced tolerability to other IFNs.  相似文献   
8.
Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are two hereditary disorders in which photosensitivity is associated with distinct clinical and cellular phenotypes and results from genetically different defects. We have identified the primary molecular alteration in two patients in whom clinical manifestations strongly reminiscent of a severe form of XP were unexpectedly associated with the CS cellular phenotype and with a defect in the CSB gene. Sequencing of the CSB -coding region in both cDNA and genomic DNA showed that these patients had identical alterations to those in a patient with the clinical features of the classical form of CS. These data, together with fluorescence in situ hybridization analysis, demonstrated that the two siblings with XP as well as the CS patient were homozygous for the same CSB mutated allele, containing a silent C2830T change and a nonsense mutation C2282T converting Arg735 to a stop codon. The finding that the same inactivating mutation underlies different pathological phenotypes indicates that there is no simple correlation between the molecular defect and the clinical features. Therefore, alterations in the CSB gene give rise to the same repair defect at the cellular level but other genetic and/or environmental factors determine the pathological phenotype.  相似文献   
9.
Experimental research has recently shown that acupuncture induces the formation of o-pioid-like peptides in animals.The role ofβ-endorphin in the mechanism of acupuncture is discussed:some authors maintain the hormonal hypothesis,others the role of neurotransmltters and,up to thepresent,no convincing evidence for either hypothesis has been demonstrated.In order to provide fur-ther evidence,we tested the β-endorphin levels and other parameters(VLP,lymphocyte subsets,NKcells and phagocyte activity of monocytes)in a group of 90 patients suffering from various painful dis-orders treated with acupuncture.Zusanli(ST 36)and Hegu(LI 4)acupoints were selected.A homo-geneous group of 30 subjects was used as control.Evaluation of the above parameters was made with3 series of blood tests;before treatment,30 minutes and 24 hours after acupuncture treatment.In theacupuncture group,the following results were achieved: a)A considerable increase in β-endorphin levels,which remained high even 24 hours afteracup  相似文献   
10.
BACKGROUND: Broad is the spectrum of congenital chest wall deformities. Fortunately the severe life-threatening deformities (i.e. ectopia cordis and Jeune's disease) are rarer than the more frequent pectus excavatum and carinatum. Funnel chest is the most common anterior chest wall deformity, it results from posterior depression of the sternum and cartilages, from the third to the eighth; it occurs more frequently in boys than in girls (4:1 ratio). While the deformity may be recognizable at birth, especially during crying spells, it progressively worsens during childhood, producing, sometimes, respiratory and cardiac impairment. METHODS: The authors report their experience, from April 1970 to December 1998, in correction of Pectus Excavatum using a single surgical technique, at the Borgo Roma Hospital of Verona. During this period 51 patients (mean age 14 years) affected by this deformity, were treated performing a sterno-chondroplasty with internal fixation. Most of the patients (94%) required operation for the esthetic and psychological reasons only. The grade of funnel chest (according to the Chin Classification) was: type I in 59.6% of patients, type II in 31.4% and type III in 11.7%. The surgical technique consisted in the modification of the Ravitch's technique (subperichondrial cartilage resection, transverse osteotomy with internal stainless steel strut fixation). We considered the intervention advisable to correct an existing defect or to prevent its progression. We don't think, in fact, that spontaneous recession of the deformity may occur. RESULTS: The follow-up varied from 4 to 18 years. The result was classified according to the classification of Humphreys and it was excellent in 64.7%, good in 17.7%, fair in 9.8% and poor in 7.8%. CONCLUSIONS: This technique proved to be safe and effective, it can be performed with no mortality, very low complication rate and satisfactory results.  相似文献   
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