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1.
A case of Rubinstein‐Taybi syndrome associated with growth hormone deficiency in childhood 下载免费PDF全文
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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5.
Flavia Temperilli Aldona Rina Isabella Massimi Anna Lisa Montemari Maria Luisa Guarino Alessandra Zicari 《Platelets》2015,26(8):783-787
Serum thromboxane-B2 (TxB2), together with arachidonic acid (AA)-induced platelet aggregation, are, at the moment, the most used tests to identify patients displaying high on-aspirin treatment platelet reactivity (HAPR). Both tests are specific for aspirin action on cyclooxygenase-1. While the correlation between serum TxB2 assay and clinical outcome is established, data are conflicting with regard to aspirin treatment and a possible association with AA-stimulated platelet markers and clinical outcome. To understand such discrepancy, we performed a retrospective study to compare both assays. We collected data from 132 patients receiving a daily dose of aspirin (100?mg/day) and data from 48 patients receiving aspirin on alternate days. All Patients who received a daily dose of aspirin were studied for AA-induced platelet aggregation together with serum TxB2 levels and AA-induced TxB2 formation was also studied in 71 patients out of entire population. Consistent with recommendations in the literature, we defined HAPR by setting a cut-off point at 3.1?ng/ml for serum levels of thromboxane B2 and 20% for AA-induced platelet aggregation. According to this cut-off point, we divided our overall population into two groups: (1) TxB2?<?3.1?ng/ml and (2) TxB2?>?3.1?ng/ml. We found low agreement between such tests to identify patients displaying HAPR. Our results show that AA-induced platelet aggregation >20% identify a smaller number of HAPR patients in comparison with TxB2. A good correlation between serum TxB2 and arachidonic acid-induced TxB2 production was found (r?=?0.76619). 相似文献
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Inflammation but not obesity or insulin resistance is associated with increased plasma fibroblast growth factor 23 concentration in the elderly 下载免费PDF全文
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Jan Jozef Braszko Anna Walesiuk Przemyslaw Wielgat 《Journal of the renin-angiotensin-aldosterone system》2006,7(3):168-174
This study tests the hypothesis that the facilitation of learning and improvement of memory observed after an intracerebroventricular (i.c.v.) injection of angiotensin II (Ang II) is, in fact, caused by its derivative angiotensin IV (Ang IV). We ran two memory tests as well as an auxiliary test assessing motor performance in rats injected (i.c.v., 1 nmol in 2 microl saline) with Ang II or Ang IV. There were separate groups receiving peptide or saline five, 10 and 15 minutes before testing. Ang IV significantly increased step-through latencies in a passive avoidance paradigm as well as improved discrimination between familiar and unfamiliar objects in an object recognition test in all groups showing better retrieval of memory of aversive as well as appetitive stimuli in the peptide-treated groups regardless of the time of its injection. In contrast, rats treated with Ang II demonstrated significant improvement of memory of aversive and appetitive stimuli in the same tests only 15 minutes after its i.c.v. injection, with no effect in the groups injected five minutes before testing and slight efficacy in those injected 10 minutes before the test. Numbers of crossings, rearings and bar approaches in an open field were similar both in the peptide-treated and control groups making it unlikely that changes in motor performance affected the memory tests. In line with the present views on the intracellular metabolism of Ang II, these results suggest degradation to Ang IV by aminopeptidases A and N is necessary before the cognitive effects can occur. 相似文献
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Anna Maria Lavezzi Giulia Ottaviani Lorella Terni Luigi Matturri 《International journal of developmental neuroscience》2006,24(6):365-371
The aim of this study was to investigate the histological and biological features of the human cerebellar cortex development and differentiation. We analyzed 52 brains of fetal and infant death victims, aged from 17 gestational weeks to 12th postnatal month. In particular, in the cerebellar cortex at different ages we evaluated, besides the structural aspects, the expression of several biomarkers implicated in proliferative processes (c-fos, PCNA and apoptosis). We observed morphological patterns progressively evolving every month, from the indefinite structure of the second gestational trimester to the four-layered structure (external granular layer, molecular layer, Purkinje cell layer, internal granular layer) of the late fetal cortex and subsequently to the three-layered postnatal definitive morphology, due to involution of the external granular layer. The evaluation of the biological features of the cerebellar cortex showed high proliferative activity mainly confined to the transient external granular layer in prenatal life, and high apoptotic index after birth. Thus, the histological examination, better with the support of biomarker investigations, allows with accuracy to describe the dynamic sequence of steps that occur in human cerebellar cortex development and to establish in each case the age, namely the pre- or postnatal month of life. Consequently, we can diagnose delayed or altered processes of differentiation during the development of the human cerebellar cortex. 相似文献
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