Ceramide composition of the psoriatic scale

This paper investigates the ceramide composition of the psoriatic scale compared with that of normal human SC. A method was optimalized, based on TLC separation followed by densitometry, allowing the provision of good resolution and quantification of ceramide fractions from both normal and pathological specimens. Seven ceramide fractions were isolated and submitted to compositional analysis. The obtained results suggested a revisitation of previous ceramide designation. Therefore a simple classification is suggested, based on grouping ceramides carrying structural similarities under common codes. According to these rules, ceramides were grouped into five classes designated as: (1) Cer[EOS], which contains ester-linked fatty acids, ω-OH fatty acids and sphingosines; (2) Cer[NS], which contains non-OH fatty acids and sphingosines; (3) Cer[NP], which contains non-OH fatty acids and phytosphingosines; (4) Cer[AS], which contains α-OH fatty acids and sphingosines; (5) Cer[AP], which contains α-OH fatty acids and phytosphingosines. Analysis of ceramides from the psoriatic scale, compared to those from normal human SC, resulted in an impairment of the Cer[EOS] content as well as of the ceramides containing phytosphingosine, with concurrent increase in ceramides containing sphingosine, being the total amount maintained identical. Since one of the suggested pathways for phytosphingosine biosynthesis involves the water addition to the corresponding sphingosine double bond, we can speculate that the observed alterarion is due to a deranged water bioavailability, associated with psoriaris.     

低能量He—Ne激光血管内照射治疗银屑病21例报告

21例寻常型银屑病患者,经用He－Ne激光血管内照射,功率3．5－5mw,每日照射一次,每次1小时,10次一疗程,同时伴用vitc2givq．d及鼻吸氧,二疗程间休息4－7天,经5－35次治疗,近期疗效：近期痊愈5例（23．81％）,显效6例（28．57％）,好转10例（47．62％）,总有效率100％,复发1例（4．76％）。     

Conformational insights into the inhibitory mechanism of phyto-compounds against Src kinase family members implicated in psoriasis

Abstract

Psoriasis is a chronic immune mediated disorder of the skin. There is growing evidence that the Src family tyrosine kinases (SFK) are highly upregulated in psoriasis. The SFK are the key components of the signaling pathways triggering cell growth and differentiation in addition to the immune cascades. In the current work, the interactions between SFK and selective phyto-compounds were studied using molecular docking approach. Based on the results of docking and binding energy calculations quercetin was identified as potential lead compound. To get a deeper insight into the binding of quercetin with the SFK, a combined molecular dynamics and binding free energy calculations were performed. The binding of quercetin disrupted the intra-molecular contacts making the SFK compact except Src kinase. The MM/PBSA free energy decomposition analysis highlighted the significance of hydrophobic and polar residues which are involved in the binding of quercetin. An experimental validation was carried out against the activated forms of Fyn, Lyn and Src kinases, the top three proteins which showed high preference for quercetin. The flow cytometry analysis showed that the expression levels of Fyn, Lyn and Src kinases were dramatically increased in HaCaT cells. However, the treatment of quercetin at the concentration of 51.65 µM for 24?h markedly decreased their expression in HaCaT cells. Besides, similar results were also observed when the HaCaT cells were treated with the kinase inhibitor Ponitinib (1.43 µM) for 24?h.

Communicated by Ramaswamy H. Sarma     

凉血活血汤联合阿维A胶囊治疗银屑病的临床疗效及其机制研究

目的:探讨凉血活血汤联合阿维A胶囊治疗银屑病的临床疗效及其可能作用机制。方法:选择2012年7月~2015年11月于我院就诊的银屑病患者60例,按照就诊先后顺序分为实验组与对照组,每组各30例,实验组患者使用凉血活血汤联合阿维A胶囊进行治疗,对照组患者仅给予阿维A胶囊进行治疗。比较治疗前后两组患者血清白细胞介素17(IL-17)、白细胞介素22(IL-22)、白细胞介素23(IL-23)及血管内皮因子(VEGF)水平,同时比较两组患者的不良反应发生率及临床总有效率。结果:与治疗前相比,两组患者血清IL-17、IL-22、IL-23及VEGF水平均降低;治疗结束后与对照组相比,实验组患者血清IL-17、IL-22、IL-23及VEGF水平较低(P0.05);且与对照组相比,实验组患者的不良反应发生率较低(P0.05);临床总有效率较高(P0.05)。结论:凉血活血汤联合阿维A胶囊能明显提高银屑病患者的临床疗效,且安全性较高,可能与其降低血清IL-17、IL-22、IL-23及VEGF水平有关。     

Biological roles of APP in the epidermis

The amyloid precursor protein (APP) was initially detected in cells of the central nervous system where it is considered to be involved in the pathogenesis of Alzheimer's disease. However, APP is also found in peripheral organs with exceptionally strong expression in the mammalian epidermis where it fulfils a variety of distinct biological roles. Full length APP appears to facilitate keratinocyte adhesion due to its ability to interact with the extracellular matrix. The C-terminus of APP also serves as adapter protein for binding the motor protein kinesin thereby mediating the centripetal transport of melanosomes in epidermal melanocytes. By the action of alpha-secretase sAPPalpha, the soluble N-terminal portion of APP, is released. sAPPalpha has been shown to be a potent epidermal growth factor thus stimulating proliferation and migration of keratinocytes as well as the exocytic release of melanin by melanocytes. The release of sAPPalpha can be almost completely blocked by inhibiting alpha-secretase with hydroxamic acid-based zinc metalloproteinase inhibitors. In hyperproliferative keratinocytes from psoriatic skin this inhibition results in normalized growth.     

吴茱萸次碱软膏对小鼠尾部鳞片银屑病模型的治疗作用

目的：吴茱萸次碱（Rutaecarpa RUT）是芸香科植物吴茱萸的主要成分,它可激活辣椒素受体促进降钙素基因相关肽（CGRP） 等神经递质的释放来发挥药理作用。本实验的目的为观察吴茱萸次碱软膏对小鼠银屑病模型治疗作用。方法：通过药剂学方法制 成了不同浓度（2%, 5%, 10%）RUT 软膏,在小鼠尾部与背部银屑病模型给药14 天,观察小鼠尾部颗粒层形成的变化,给药结束后 取小鼠背部皮肤组织匀浆后采用放射免疫方法检测CGRP水平变化,并且取小鼠血浆检测CGRP水平变化。结果：不同浓度的吴 茱萸次碱软膏均能促进小鼠尾部颗粒层形成（P<0.05）,并且浓度为5%与10%的RUT 软膏能显著降低小鼠背部CGRP 含量（P<0. 05）,但是其对小鼠血浆的CGRP 没有影响。结论：吴茱萸次碱外用对小鼠银屑病模型有一定的治疗作用,这种作用与其促进小鼠 皮肤CGRP 释放而导致其含量降低有关。     

Effects of a mixture of fatty acids from sugar cane (Saccharum officinarum L.) wax oil in two models of inflammation: Zymosan-induced arthritis and mice tail test of psoriasis

A mixture of fatty acids obtained from sugar cane (Saccharum officinarum L.) wax oil (FAM), in which the main constituents are palmitic, oleic, linoleic, and linolenic acids, was evaluated in two models of inflammation: zymosan-induced arthritis and in the tail test for psoriasis, both on mice. In the first model, FAM significantly reduced zymozan-induced increase of beta glucuronidase (DE(50) 90+/-7 mg/kg). Histopathological studies showed inhibition in cellular infiltration and reduction of synovial hyperplasia and synovitis, whereas in the second test, histopathological and ultrastructural studies showed that topical application of FAM induced orthokeratosis with the presence of keratohyalin granules in the previously parakeratotic adult mouse tail, and without effects on epidermal thickness. The ED(50) of FAM in this model was 155+/-10 mg. The results of our studies showed that topical application of FAM exerts an important anti-inflammatory activity in both tests without evidence of irritant effects. The anti-inflamatory effects exerted by FAM may be due to its inhibitory effects on arachidonic acid metabolism. To our knowledge, this is the first report on the anti-inflammatory effect of sugar cane by-products in experimental models of arthritis and psoriasis.