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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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3.
The efficacy of radiology in evaluating dysphagia was studied in 86 patients by comparison to endoscopic findings. In the 66 patients with endoscopic abnormalities radiology was correct in 54, for a sensitivity of 82%. Sensitivity of radiology improved to 95% if mild esophagitis was excluded. In the 20 patients with normal endoscopy, radiology was normal in 18 (90%). Thus radiology proved to be a reliable means of evaluating the esophagus in patients with dysphagia.  相似文献   
4.
We investigate the controlled release of lidocaine hydrochloride from the doped silica-based xerogels. In the xerogel preparation, tetraethoxysilane (TEOS), methyltriethoxysilane (MTES), and propyltriethoxysilane (PTES) are used as precursors, and a nonionic surfactant Igepal CO 720 is used as a dopant. The experimental results suggest that the release of lidocaine hydrochloride can be easily controlled by partially substituting TEOS with the organosilanes, and/or by adding the dopant. Adding the organosilane precursors lowers the release of both the drug and the surfactant in the order of TEOS, MTES/TEOS, and PTES/TEOS xerogels. The release from the PTES/TEOS xerogels is much lower than that from the other xerogels. The release of lidocaine hydrochloride is obviously suppressed by the addition of Igepal CO 720, while the release of Igepal CO 720 is slightly promoted by the addition of the drug. The overall release process is found to be diffusion-controlled, and the release behaviors can be well explained by considering the effects of the textual properties of the xerogels and the interactions among the drug, the surfactant, and the xerogel matrices.  相似文献   
5.
BACKGROUND AND PURPOSE: Thyroidectomy is a common treatment for thyroid disorders in Taiwan, and constitutes a significant percentage of medical expenses. This study investigated the characteristics of thyroidectomy in Taiwan. METHODS: A total of 21 senior general surgeons from 16 medical centers and 5 regional hospitals participated. One surgeon from each hospital reviewed the hospital's medical records of thyroid operations performed in the year 2001. Medical records for 3846 thyroidectomies were retrospectively analyzed, including surgical indications and modalities, complications, pathology reports, and the use of antibiotics. RESULTS: Most of the patients were women (85%). Indications for surgery included proven malignancy (9%), suspicious malignancy (30%), evident compression symptoms (20%), hyperthyroidism (20%), and cosmetic reasons (12%). The majority of patients (78%) underwent a surgical procedure with lobectomy or bilateral thyroidectomy; 13% had unilateral partial thyroidectomy. Prophylactic antibiotics were administered in 46% of procedures, and continued postoperatively in 12%. Postoperative complications occurred in 12% of patients. Hypocalcemia was the most common complication (8%), and its incidence was significantly correlated with the frequency of total thyroidectomy (p < 0.01). Complete pathology reports for the thyroidectomized specimens were available in only 65% of the cases. The frequency of cosmetic reasons for surgery, unilateral subtotal resection, routine antibiotic administration, and incomplete pathology reports were significantly higher in regional hospitals than in medical centers. CONCLUSIONS: Reduction in the high rates of cosmetic reasons for surgery, unilateral partial thyroidectomy, incomplete pathology reports, and use of antibiotic prophylaxis are needed to improve the quality of thyroidectomy in Taiwan.  相似文献   
6.
Pneumocephalus is a very rare complication of video-assisted thoracoscopic surgery (VATS). A 66-year-old man developed pneumocephalus secondary to thoracoscopic excision of a neurogenic tumor in the posterior mediastinum. Pneumocephalus was diagnosed by brain computed tomography. Neurosurgical intervention was performed after conservative therapy had failed. The patient's condition had resolved without any neurologic sequelae 2 years later. When a patient has a relatively large amount of chest tube drainage and neurologic symptoms after VATS, the possibility of pneumocephalus due to cerebrospinal fluid leakage must be considered.  相似文献   
7.
Bradyarrhythmia requiring permanent pacing after heart transplantation remains a common problem. Sinus node dysfunction is the most common indication, and late onset of atrioventricular (AV) block has rarely been reported. We report the case of a patient who developed advanced AV block at 41 months after transplantation. Right bundle branch block with progressive increase of QRS complex duration was noted in serial electrocardiograms. At the time of late AV block development, the patient did not have acute rejection and coronary angiogram was normal. The mechanism of late onset of AV block is unclear, but it may be caused by progressive conduction.  相似文献   
8.
The growth hormone(GH), produced by the growth hormone cell in pars distalis of the adenohypophysis, acts on the sugar, protein and fat metabolism in various degrees. After trauma, the GH has relations with the energy supply, the maintenance of nitrogen balance, the tissue repair and the body resistance. However, pathological study on the GH cell after burn injury is rare in the literature so far. The purpose of the present investigation is to take a dynamic observation on the ultrastructural changes of the rabbit GH cell after napalm burn within one week. 46 male rabbits were used and divided into two groups, napalm burn group (N = 36) and control group (N = 10). The former is inflicted with 3rd degree burn covering 30% TBSA. The animals of former group were sacrificed at 3, 6, 12, 24, 48, 72, 96, 120, 168 hours postburn respectively. Using the light and electron microscopy and stereological method, the results revealed that: (1) the synthesis activity in GH cell was enhanced, the process of secretion was rapid, and the rate of granule maturation was increased; (2) the nude GH granules were found both in the sinusoids and the endothelial cells; (3) the newly formed mitochondria may be originated from the Golgi complex, and the newly formed Golgi complex from the reutilization of the plasma membrane components; (4) some endothelial cells manifested degeneration, and the others showed in active condition; (5) under the light microscopy, the distribution of the lower tint-phil GH cells had its regional-characteristics.  相似文献   
9.
Prolongation of the action potential duration of dorsal root ganglion (DRG) neurons by low (nM) concentrations of opioids occurs through activation of excitatory opioid receptors that are positively coupled via Gs regulatory protein to adenylate cyclase. Previous results suggested GM1 ganglioside to have an essential role in regulating this excitatory response, but not the inhibitory (APD-shortening) response to higher (μM) opioid concentrations. Furthermore, it was proposed that synthesis of GM1 is upregulated by prolonged activation of excitatory opioid receptor functions. To explore this possibility we have utilized cultures of hybrid F11 cells to carry out closely correlated electrophysiological and biochemical analyses of the effects of chronic opioid treatment on a homogeneous population of clonal cells which express many functions characteristic of DRG neurons. We show that chronic opioid exposure of F11 cells does, in fact, result in elevated levels of GM1 as well as cyclic adenosine monophosphate (AMP), concomitant with the onset of opioid excitatory supersensitivity as manifested by naloxone-evoked decreases in voltage-dependent membrane K+ currents. Such elevation of GM1 would be expected to enhance the efficacy of excitatory opioid receptor activation of the Gs/adenylate cyclase/cyclic AMP system, thereby providing a positive feedback mechanism that may account for the remarkable supersensitivity of chronic opioid-treated neurons to the excitatory effects of opioid agonists as well as antagonists. These in vitro findings may provide novel insights into the mechanisms underlying naloxone-precipitated withdrawal syndromes and opioid-induced hyperalgesia after chronic opiatf addiction in vivo. © 1995 Wiley-Liss, Inc.  相似文献   
10.
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