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
ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology. 相似文献
Objective: To report a case of labour induction during extracorporeal membrane oxygenation (ECMO) support in a patient with acute respiratory distress syndrome (ARDS) caused by influenza and review of the literature.
Methods: Case report and the literature search of all English articles on delivery while on ECMO in patients with ARDS caused by influenza.
Results: A 25-year-old pregnant woman was initiated with ECMO due to severe ARDS caused by influenza A (H1N1) virus. When the patient had symptoms of colporrhagia and uterine contractions, the medical team decided to start labour induction while on ECMO. There were in total five case reports identified. Maternal oxygenation was improved after delivery and ECMO was successfully discontinued.
Conclusions: Maternal oxygenation was improved after delivery, which may be beneficial to reduce the duration of ECMO. Caesarean section (CS) may be the most used mode and labour induction could be another option. The procedure should be performed by an experienced ECMO team, cooperating with the obstetrician, anaesthesiologist, and ICU doctors. 相似文献
BACKGROUND: Three dimensional skin equivalents are widely used in dermatopharmacological and toxicological studies and as autologous transplants in wound healing. In pharmacology, there is tremendous need for monitoring the response of engineered skin equivalents to external treatment. Transplantation of skin equivalents for wound healing requires careful verification of their quality prior to transplantation. Optical coherence tomography (OCT) is a non-contact, non-destructive imaging technique for living tissues offering the potential to fulfill these needs. This work presents an analysis of OCT for high-resolution monitoring of skin equivalents at different stages during the culture process. METHODS: We developed a high-resolution OCT imaging setup based on a commercially available OCT system. A broadband femtosecond laser light source replaces the original superluminescence diode. Tomograms of living skin equivalents were recorded with an axial resolution of 3 mum and correlated with histology and immunofluorescence images. Comparison with standard low-resolution OCT is presented to emphasize the advantages of high-resolution OCT for this application. RESULTS: OCT is particularly able to distinguish between different layers of skin equivalents including stratum corneum, epidermal and dermal layer as well as the basement membrane zone. The high-resolution OCT scans correlate closely with two key benchmarks, histology and immunofluorescence imaging. CONCLUSIONS: This study clearly demonstrates the benefits of high-resolution OCT for identifying living tissue structure and morphology. Compared with the current gold standard histology, OCT offers non-destructive tissue imaging, enabling high-resolution evaluation of living tissue morphology and structure as it evolves. 相似文献
The aim of this study was to design a new intravenous blood–gas exchange device and to estimate the design characteristics
of the device with a dimensionless function by using a substance that can be used instead of bovine blood. In addition, the
characteristics of oxygen transfer were estimated using empirical formulas and the reliability of the equations was ascertained
by comparing their output with an experiment performed using bovine blood. The dimensionless function was derived using distilled
water and bovine blood to estimate the oxygen transfer rate. Using the derived equations, the calculated oxygen transfer rates
for bovine blood and distilled water were similar for Reynolds numbers ranging from 0.7 to 7.0. Therefore, it is possible
to estimate the oxygen transfer rate in bovine blood, which is a non-Newtonian fluid, using distilled water, which is a Newtonian
fluid. Moreover, it was possible to verify the related equations because the oxygen transfer rate could be estimated using
the derived equations, according to the diameters of the various device modules. 相似文献
The aim of the study was to subclassify the soma-dendritic α2-autoreceptors in the locus coeruleus (LC) of the rat by means of antagonists. To this end, the frequency of spontaneous action
potentials was recorded extracellularly from single LC neurones in brain slices. The neurones fired spontaneously at an average
rate of 1 Hz. The selective α2-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) and noradrenaline decreased the action potential
discharge with IC50 values of 5 and 510 nM, respectively. The concentration-inhibition curves of UK 14,304 and noradrenaline were shifted to the
right by phentolamine (0.15 μM) and rauwolscine (0.15 μM) but not by prazosin (1 μM). Apparent Kd values of phentolamine were 17 nM (against UK 14,304) and 20 nM (against noradrenaline). Apparent Kd values of rauwolscine were 47 nM (against UK 14,304) and 70 nM (against noradrenaline). (+)-Oxaprotiline (1 μM) suppressed
the firing of the neurones within 10 to 33 min. In the continued presence of oxaprotiline, phentolamine and rauwolscine restored
firing with EC50 values of 120 and 250 nM, respectively. Prazosin (1 μM) again was ineffective. All three antagonist affinity estimates –
against UK 14,304, exogenous noradrenaline and endogenous noradrenaline (that accumulates in the extracellular space in the
presence of oxaprotiline) – yield an affinity order phentolamine > rauwolscine >> prazosin, prazosin being ineffective even
at a concentration of 1 μM. These findings identify the soma-dendritic α2-autoreceptors of the LC as the rat variant of the α2A/D-adrenoceptor, i.e. α2D. Not only presynaptic but also soma-dendritic α2-autoreceptors may at least predominantly be α2A/D throughout the nervous system.
Received: 3 March 1997 / Accepted: 21 April 1997 相似文献
Several cell lines secreting monoclonal antibodies (Mabs) against a major forebrain synaptic membrane (SM) glycoprotein, gp 50, have been raised. Western blots show that the Mabs react with a polypeptide doublet of Mrs 49 and 45 kDa. These polypeptides exist solely in a concanavalin A (Con A) binding form. Removal of the Con A receptors by digestion with endo-beta-N-acetylglucosaminidase H (endo H) lowers the Mrs of the glycoprotein doublet to 36.5 and 34 kDa. Western blots of 2D polyacrylamide gels indicate that gp 50 exists in several isoforms. Solid phase radioimmunoassay (RIA) and Western blots of brain subcellular fractions show the antigenic material to be concentrated in the SM fraction, but to be present in much lower amounts in synaptic junctions and postsynaptic densities. Gp 50 appears to be brain specific. Regional distribution studies show that it is present in all brain regions but is two-fold concentrated in cerebellum, brainstem and midbrain compared to forebrain. Immunocytochemical studies of several brain regions show that gp 50-like immunoreactivity is neuron specific and is concentrated in selected neuronal species, particularly granule cells. In both cerebellar and hippocampal granule cells gp 50-like immunoreactivity is localized in the perikarya and primary dendrites. Though immunocytochemistry did not show staining of synaptic regions this may be due to masking of the reactive epitope. The results are discussed in terms of the molecular properties of gp 50 and its subcellular localization in brain tissue. 相似文献