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1.
Jae Eun Choi Tyler Werbel Zhenping Wang Chia Chi Wu Tony L. Yaksh Anna Di Nardo 《Journal of dermatological science》2019,93(1):58-64
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.
3.
Andreas Karatsaidis Olav Schreurs Kristen Helgeland Tony Axéll Karl Schenck 《Journal of oral pathology & medicine》2003,32(5):275-281
BACKGROUND: Common clinical forms of oral lichen planus (OLP) and oral lichenoid reactions (OLR) are erythematous (ERY) or reticular (RET). The purpose of this study was to find histopathological changes that differ between these forms. METHODS: Epithelial thickness, epithelial proliferation rate, apoptosis, and HLA-DR expression were compared among 10 reticular and 12 erythematous lesions, and 11 normal oral mucosa samples (NOM). RESULTS: The epithelium in ERY was thinner than in NOM, whereas RET showed values between ERY and NOM. Cell proliferation increased significantly in ERY as compared with RET and NOM, with no difference between RET and NOM. Relative numbers of epithelial cell nuclei displaying visible chromatin condensation were reduced in ERY form. CONCLUSIONS: The markedly increased cell proliferation in ERY supports the notion that this form displays a higher disease activity as compared to RET. It can therefore be important to study each disease form separately. 相似文献
4.
Tony R Cucuzzella Elva G Delport Nancy Kim Julie Marley Christine Pruitt Anton G Delport 《The spine journal》2006,6(4):364-369
BACKGROUND CONTEXT: Substantial variation exists regarding the use of sedation before interventional spine techniques. Patient preference should play an important role in decision making regarding the need for sedation. However, little is known about patients' anxiety levels before spinal injections and their perceptions about the necessity of sedation. PURPOSE: To determine patient perception for need for sedation before epidural steroid injections and zygapophyseal joint injections. STUDY DESIGN/SETTING: Survey of consecutive spinal injection patients in an outpatient spine center. PATIENT SAMPLE: 500 consecutive lumbar, thoracic, and cervical patients receiving spinal injections. OUTCOME MEASURES: A 12-item questionnaire assessing patients' perceived anxiety before to a spinal injection. METHODS: Subjects were given the questionnaire after their spinal injection. Percentages requesting sedation for a first and potential second procedure were assessed. Additionally, anxiety level and pain rating, location of injection, age, sex, and other medication use were analyzed to determine the effect on the request for sedation. RESULTS: 17% of patients questioned requested sedation before an injection, and 28% would request sedation if they were to have a second injection. CONCLUSIONS: Routine sedation before diagnostic and therapeutic injections is not necessary as the majority of patients would not request sedation before the procedure when given the option. However, in some patients sedation is indicated, and all patients would benefit from educational material on sedation before the injection. 相似文献
5.
Release of cholecystokinin from rat cerebral cortex in vivo: role of GABA and glutamate receptor systems 总被引:1,自引:0,他引:1
Using cortical cups in chloralose-urethanized rats, the in vivo release of cholecystokinin-like immunoreactivity (CCK-LI) from cerebral cortex was examined. Resting levels of cholecystokinin-like immunoreactivity ranged from 20 to 30 pg/20 min sample. The addition of potassium (40 mM) in excess, resulted in a highly significant elevation in the levels of CCK-LI in the cortical superfusate. Deletion of calcium and the substitution of cobalt (10 mM), resulted in a significant reduction in both resting release and the release otherwise evoked by the addition of potassium. Focal electrical stimulation of the cortex (20 Hz), resulted in a significant (1.9 +/- 0.2-fold, n = 8) increase in the levels of CCK-LI. The addition of glutamate (10(-6)-10(-4) M) of kainic acid (10(-8)-10(-6) M), also resulted in significant elevations in the levels of CCK-LI. The co-administration of a putative glutamate receptor antagonist, kynurenic acid (10(-4) M) resulted in a significant reduction in the levels of release otherwise evoked by the addition of glutamate, but not by electrical stimulation. The addition of GABA (10(-5)-10(-3) M) resulted in a dose-dependent decrease in the resting release of CCK-LI, and the release evoked by glutamate. Picrotoxin (10(-6)-10(-4) M), resulted in a highly significant increase in the levels of CCK-LI in the cortical effluent. These results are consistent with a tonic GABAergic inhibition of CCK-releasing neurons. The treatment of the animal with diazepam (30 mg/kg, i.p.) also resulted in a significant reduction in resting release and the release otherwise evoked by focal cortical stimulation. 相似文献
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8.
Immunity after treatment of human schistosomiasis mansoni. III. Long-term effects of treatment and retreatment 总被引:1,自引:0,他引:1
R F Sturrock R Bensted-Smith A E Butterworth P R Dalton H C Kariuki D Koech M Mugambi J H Ouma T K arap Siongok 《Transactions of the Royal Society of Tropical Medicine and Hygiene》1987,81(2):303-314
Group mean Schistosoma mansoni reinfection patterns are presented for 2 years after treatment with oxamniquine in 1981 of over 100 9- to 16-year-old Kenyan schoolchildren, and for one year after retreatment in 1983 with either oxamniquine or praziquantel when most (nearly 700) infected people in the whole community were treated. Quality control confirmed comparable Kato egg counts throughout the study. Continuing transmission after 1981 raised prevalence to nearly its original level within 6 months, but intensity remained suppressed throughout the 2 year follow-up and very few children reacquired heavy infections (greater than 400 eggs/g). Age and sex had significant effects: reinfection diminished with age, especially among boys--a pattern not apparently attributable to differential water contact. Children with heavy pretreatment infections tended to develop heavy reinfections but this trend was not statistically significant on a group basis, nor were similar trends during the period of less pronounced transmission following the 1983 community treatment. Oxamniquine was equally effective in children receiving it in both 1981 and 1983, and the efficacy of praziquantel resembled that of oxamniquine. In this area of Kenya, repeated chemotherapy will be needed to contain transmission, probably annually or biennially, unless supplemented with other, effective control measures. These findings confirm the beneficial effects of treating even a limited segment of a community at intervals of a year or more without necessarily stopping transmission. They are also compatible with recent findings on potential immune mechanisms in man. 相似文献
9.
M Vijaya Lakshmi MRCP G V Sridharan MRCP D Butterworth MRCP 《International journal of clinical practice》1993,47(3):164-165
Gallstones are common and their incidence increases with age.1 Fifty per cent of these stones are in the common bile duct (CBD) in the elderly.2 Most of them are silent but with time there is an increasing chance of developing symptoms which are more likely to be serious in the elderly.3 Failure to relieve mechanical obstruction of bile flow may lead to secondary biliary cirrhosis.4 It has been estimated that on average secondary biliary cirrhosis develops some seven years after the onset of obstruction from a stricture, four and half years after gallstone obstruction and 10 months after the onset of malignant stricture.5 The characteristic features are the pathological findings of portal-portal linkages, with a pattern of monolobular cirrhosis and the preservation of normal vascular relationships.6 Secondary biliary cirrhosis may lead to hepatic insufficiency and portal hypertension with the resultant complications, such as bleeding oesophageal varices, hypersplenism with pancytopenia, ascites and encephalopathy. We describe a patient in whom the diagnosis was not suspected until laparotomy and confirmed only at autopsy. 相似文献
10.
Ladenstein Ruth; Pearce Rachel; Hartmann Olivier; Patte Catherine; Goldstone Tony; Philip Thierry 《Blood》1997,90(8):2921-2930