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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.
《Clinical neurophysiology》2020,131(1):213-224
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
3.
目的:探讨活性氧(ROS)对人类精子线粒体tRNALeuUUR基因的氧化损伤。方法:采用Percoll梯度离心法筛选具有正常生理功能的精子,作为正常精子模型,并分为损伤组20例和对照组20例,分别加入次黄嘌呤-黄嘌呤氧化酶体系或不予处理,37℃有氧环境中孵育60min。分别提取精子DNA,以Fpg酶切损伤碱基并采用接头介导PCR(LM-PCR)检测线粒体tRNALeuUUR基因的氧化损伤。采用Rhodamine(Rh123)荧光探针标记精子,通过流式细胞仪检测线粒体膜电位,观察精子的功能。结果:与对照组相比,损伤组精子孵育后线粒体膜电位明显降低[(116.27±11.72)%vs(64.00±4.88)%,P<0.05]。Fpg酶切和LM-PCR显示精子线粒体tRNALeuUUR基因损伤。结论:ROS可能通过对精子线粒体tRNALeuUUR基因氧化损伤而影响精子功能(线粒体膜电位明显降低),从而引起不育。 相似文献
4.
Michele Clark Margaret Steinberg Noelene Bischoff 《Australian Occupational Therapy Journal》1997,44(3):132-141
This study examined the interface between acute hospital care and return to home in relation to elderly patients' perceived ability and preparedness to cope at home. Seventy-six (n = 76) elderly patients aged 60 years and over were randomly recruited from a large Queensland hospital and interviewed prior to discharge about their perceived health, functional status and their ‘readiness’ to cope at home. They were followed up at home 7–10 days post-discharge. Comparisons were made between a number of measures at discharge and post-discharge. Although the majority of patients indicated that they would cope very well upon discharge, a large number of patients reported experiencing considerable difficulty with activities of daily living, particularly instrumental activities of daily living prior to and especially after discharge. The self-reported health status of patients similarly deteriorated between discharge and follow-up. Despite a large number of patients experiencing functional limitations, few were referred to hospital or community-based therapy services. Some policy implications are explored. 相似文献
5.
W. Nörenberg Ernst Schöffel Bela Szabo Klaus Starke 《Naunyn-Schmiedeberg's archives of pharmacology》1997,356(2):159-165
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 K
d values of phentolamine were 17 nM (against UK 14,304) and 20 nM (against noradrenaline). Apparent K
d 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
6.
Nuttan K. Tanna 《Pharmacy World & Science》2005,27(1):4-6
The evaluation of healthcare practice and service delivery is fraught with difficulties. Service development and / or delivery occurs within socially dynamic settings which are in a continual state of change. Service development also often involves large elements of improvisation. The action research approach is useful for health service research, as it supports collaboration between researchers and practitioners, and not only allows but makes explicit that the action researcher has both roles within the setting being studied. This paper discusses action research methodology and offers insight into principles that favor its use for service delivery development. This includes consideration of the interactive variables within studies of health care systems and the importance of
evaluating relationships between stakeholders to understand how these factors or variables, which cannot be controlled for, are responsible for successful development of the service. Action research facilitates change and helps bridge the heory--practice gap. With the current dynamic changes within both the pharmacy profession and national health services, researchers may find the action research technique of value
when considering new roles and innovative ways of engaging in collaborative, multi-disciplinary working to improve delivery of patient care.Accepted july 2004 相似文献
7.
8.
目的 探讨实验性内听动脉阻断与术后听力改变的关系及术中听觉监控的方法。方法 实验兔乙状窦后进路暴露小脑桥脑角,下压小脑暴露内听道及第Ⅷ神经复合体,分辨出内听动脉,予阻断不同时间,分别行蜗神经直接复合动作电位(DCAP)和畸变产物耳声发射记录(DPOAE)。结果对照组DCAPN1波潜伏期值无明显改变。内耳血供阻断10s和30s组在压迫开始后3min,DCAPN1波潜伏期值均恢复为初始值。内耳血供阻断1min组在压迫开始后3h,DCAPN1波潜伏期值未恢复为初始值假手术组DPOAE幅值无明显改变,内耳血供阻断10s、30s对DPOAE幅值无影响,内耳血供阻断1min使得DPOAE幅值下降结论兔内耳血供阻断1min可能造成兔听觉不可逆损伤。DCAP、DPOAE能有效、持续地监控内耳血供阻断,是耳神经外科手术中实用的听觉监测手段。 相似文献
9.
目的探讨乳头溢液的渗断和治疗方法,为合理的治疗提供科学依据。方法回顾分析手术治疗的207例乳头溢液病例资料。结果(1)在非哺乳期间发生乳头溢液多属病理性溢液;(2)通过美蓝法或平针头指示法行区段切除术,安全准确。结论(1)乳头溢液特别足血性溢液应手术治疗.对早期发现和早期治疗乳腺癌有鼋要的临床意义。(2)乳头溢液伴肿块者,不沧年龄大小、溢液性质均应手术治疗。 相似文献
10.
Receiver operating characteristic curves and accuracy parameters were computed for traditional sperm characteristics (concentration, motility, morphology) and the number of peroxidase negative cells, and the concentration of adenosine triphosphate (ATP) in semen from populations of fertile and infertile men, and men who achieved a pregnancy after varicocele treatment. The percentage and concentration per millilitre of spermatozoa with rapid linear progressive motility, and the ATP concentration, provided the best discrimination between fertile and treated fertile from infertile men. The misclassification rate was higher for sperm morphology, total progressive motility and viability, whereas sperm concentration and the total sperm count per ejaculate had the worst discriminating power. The number of peroxidase negative cells per 100 spermatozoa was highly specific in identifying men who achieved pregnancy after varicocele treatment. The lower limit of normality of sperm characteristics was remarkably different between fertile men and men achieving pregnancy after treatment or during infertility work-up. 相似文献