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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.
Cooking processes that gelatinize granules or disrupt structure might increase the glucose and insulin responses because a disruption of the structure of starch by gelatinization increases its availability for digestion and absorption in the small intestine. We hypothesized that the uncooked form of rice, which has a relatively low degree of gelatinization even though in powder form, would result in lower metabolic glucose and insulin responses compared with cooked rice (CR). To assess the effects of the gelatinization of rice on metabolic response of glucose and insulin, we investigated the glucose and insulin responses to 3 rice meals of different gelatinization degree in female college students (n = 12): CR (76.9% gelatinized), uncooked rice powder (UP; 3.5% gelatinized), and uncooked freeze-dried rice powder (UFP; 5.4% gelatinized). Uncooked rice powders (UP and UFP) induced lower glucose and insulin responses compared with CR. The relatively low gelatinization degree of UPs resulted in low metabolic responses in terms of the glycemic index (CR: 72.4% vs UP: 49.7%, UFP: 59.8%) and insulin index (CR: 94.8% vs UP: 74.4%, UFP: 68.0%). In summary, UPs that were less gelatinized than CR induced low postprandial glucose and insulin responses.  相似文献   
3.
The authors describe a very rare case of choreoathetotic movements which appeared in an epileptic in strict relationship to a toxic concentration of diphenylhydantoin in the serum. These movements were reversible and disappeared after reduction of drug dose and its serum concentration falling to the therapeutic range.  相似文献   
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Reduction mammaplasty by central pedicle flap with short submammary scar   总被引:2,自引:0,他引:2  
Reduction mammaplasty was performed in 30 patients by combining the central pedicle flap method with the short submammary scar (3-S) technique to avoid the common drawbacks of currently popular dermoglandular procedures. Reduction was accomplished by using perforating vascular branches from the pectoralis major muscle and its fascia supplying the nipple and breast parenchyme instead of the subdermal plexus. The central vascular pedicle supplying the nipple-areola complex was preserved. Only the periphery of the breast parenchyme was resected circumferentially, with the exception of the inferolateral portion, so as not to injure the sensory nerve. The remaining breast parenchyme was preserved in an inverted cone shape. The nipple-areola complex was safely transposed with great freedom, and the amount of resection was accurately adjusted for symmetry. No cases of nipple-areola complex sensory change occurred postoperatively, and lactation is possible because of preservation of the lactiferous ducts. The length of postoperative scars was reduced by using the short submammary scar technique. We believe this combined method is ideal in patients requiring resections ranging from 200 to 600 g per breast with good skin elasticity and moderate degree of ptosis.Presented at the Sixth Asian Pacific Congress of the International Confederation for Plastic and Reconstructive Surgery, in Seoul, Korea, October 1993.  相似文献   
8.
1‐Benzyl‐4‐hydroxy[2‐14C]piperidine, a useful intermediate in labeled compound synthesis, was prepared from [14C]formaldehyde in high yield. The distribution pattern of 14C in the product is consistent with a mechanism involving reversible iminium ion formation and rapid equilibration of the iminium ion through a cationic aza‐Cope rearrangement. These steps precede the rate‐determining intramolecular cyclization step. SCH 351125 is a potent, selective CCR5 receptor antagonist with potential as a treatment for HIV infection. [14C]SCH 351125, required for metabolism studies, was prepared from 1‐benzyl‐4‐hydroxy[2‐14C]piperidine in six steps. [14C]SCH 351125 is a mixture of four atropisomers. Preparation of [14C]SCH 351125 besylate salt of the desired atropisomer pair is also described. Copyright © 2007 John Wiley & Sons, Ltd.  相似文献   
9.
Muscularis mucosa of urinary bladder. Importance for staging and treatment   总被引:1,自引:0,他引:1  
We report the results of a histologic evaluation of muscle (muscularis mucosa) in the lamina propria of the urinary bladder performed on 100 consecutive cystectomy specimens. Muscle fibers were found in the lamina propria lying parallel to the mucosa and forming a distinct muscularis mucosa in three cases; they were interrupted or discontinuous in 20 cases, and dispersed or scattered, forming thin bundles, in 71 cases. In six cases, there were no muscle fibers in the lamina propria. In addition, we noticed that the lamina propria contains large vessels that run along the length of the lamina propria in a continuous or interrupted fashion. When muscle fibers are present, they are associated with these vessels. Since prognosis and management of muscle invasive carcinomas (stage B) is different from that of lamina propria-invasive tumors (stage A), pathologists and urologists should be aware of the presence of a muscularis mucosa in the urinary bladder.  相似文献   
10.
We present a case of benign osteoblastoma of the occipital bone. Benign osteoblastoma is an uncommon primary bone tumor, which usually involves the vertebrae and the long bones. This tumor rarely develops in the calvaria, showing a preference for the temporal and frontal bones when it does. To the best of our knowledge, this case is only the eighth reported case of benign osteoblastoma confined to the occipital bone. A 20‐year‐old male presented with a mild tender mass lesion of the occipital area, just below the lambda. Plain X‐ray films and CT scans demonstrated an osteolytic mass surrounded by the sclerotic rim within the diploic space. MRI proved to be effective for the evaluation of the intracranial and intraosseous extensions of the tumor. However, it was very difficult to formulate a differential diagnosis against other osteoblastic tumors, or osteoid osteoma, in view of its radiological appearance. The final diagnosis was obtained by careful consideration of the histopathological characteristics of the tumor combined with its clinical and radiological features. Although generally regarded as benign, a complete resection is preferred over conventional curettage as this can guard against possible recurrence and malignant transformation.  相似文献   
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