Cytokines as therapeutic targets in skin inflammation

This review focuses on treatment targets for the most common inflammatory skin diseases, eczema and psoriasis with an emphasis on cytokines expressed in the uppermost layer of the skin which is easily accessible for diagnostic and therapeutic approaches. Recently, a significant body of research has highlighted the influence of the skin barrier and the patients’ microbiome on skin inflammatory responses and we will comment on their impact on mediator regulation. Itch is a prominent dermatology symptom which is influenced by cytokines and can via itch–scratch cycle impact on the skin barrier and mediator expression associated with damage. Taking the contribution of pruritus and superficial skin damage into account, we address cytokines as targets for stratified treatment approaches in subgroups of eczema and psoriasis.     

尿毒症皮肤瘙痒患者采取腹膜透析与血液透析治疗的效果探究

目的：探究尿毒症皮肤瘙瘁患者采取腹膜透析与血液透析治疗的临床效果,并为该病的临床治疗提供经验积累。方法：选取我院肾内科于2005年1月-2012年12月收治的52例尿毒症皮肤瘙痒患者,利用随机数字表法进行分组,分别设为研究组和对照组。其中对照组实施血液透析治疗,而研究组开展腹膜透析治疗。记录两组在治疗前和治疗后第8周末血生化客观指标及皮肤瘙痒程度,并做好对比。结果：两组在治疗前的皮肤瘙痒评分、β2-MG、PTH、p3,BUN、SCr值差异无统计学意义（P〉0．05）;治疗后,研究组皮肤瘙瘁评分为（3．4±0．8）分,对照组为（5．8±0．9）分,差异有统计学意义（P〈0．05）。治疗后,研究组β2-MG、PTH及Ps．均低于对照组,差异有统计学意义（P〈0．05）。结论：尿毒症皮肤瘙痒患者的主要致敏因子为大中分子,采取腹膜透析能够有效清除大分子物质,进而达到瘙痒程度的有效改善。     

血府逐瘀汤与赛庚啶治疗瘢痕成熟期瘙痒的比较研究

目的：比较血府逐瘀汤与赛庚啶治疗瘢痕成熟期瘙痒的效果。方法：将患者随机分为治疗组和对照组,治疗组口服血府逐瘀汤治疗瘢痕瘙痒,对照组口服赛庚啶,比较两组患者服药后的瘙痒评分及P物质浓度。结果：治疗组服药后的瘙痒评分及P物质浓度均低于对照组,差异有统计学意义（P〈0．05）.结论：血府逐瘀汤治疗瘢痕成熟期瘙痒的效果优于赛庚啶。     

盐酸非索非那定片联合胸腺肽对慢性荨麻疹患者风团及瘙痒情况的影响

目的:研究盐酸非索非那定片联合胸腺肽对慢性荨麻疹患者风团及瘙痒情况的影响分析。方法:选择2012年7月至2013年7月在我院接受治疗的慢性荨麻疹患者108例作为研究对象。以数字法随机分成观察组(54例)和对照组(54例)。对照组患者单纯服用盐酸非索非那定片,观察组在此基础上加用胸腺肽。对比两组疗效,风团和瘙痒症状总积分情况及不良反应。结果:观察组的总有效率为72.22%(39/54),显著高于对照组的53.70%(29/54),差异有统计学意义(P0.05)。两组治疗后的症状总积分均显著下降,但观察组治疗2,4周后的症状总积分均显著小于对照组,差异均有统计学意义(P0.05)。观察组的总不良反应率为9.26%(5/54),与对照组的22.22%(12/54)相比,差异无统计学意义(P0.05)。结论:盐酸非索非那定与胸腺肽联合治疗慢性荨麻疹疗效较好,值得推荐。     

Selective CB2 agonists with anti-pruritic activity: Discovery of potent and orally available bicyclic 2-pyridones

The CB2 receptor has emerged as a potential target for the treatment of pruritus as well as pain without CB1-mediated side effects. We previously identified 2-pyridone derivatives 1 and 2 as potent CB2 agonists; however, this series of compounds was found to have unacceptable pharmacokinetic profiles with no significant effect in vivo. To improve these profiles, we performed further structural optimization of 1 and 2, which led to the discovery of bicyclic 2-pyridone 18e with improved CB2 affinity and selectivity over CB1. In a mouse pruritus model, 18e inhibited compound 48/80 induced scratching behavior at a dose of 100 mg/kg. In addition, the docking model of 18e with an active-state CB2 homology model indicated the structural basis of its high affinity and selectivity over CB1.     

Enhancement of experimental pruritus and mechanically evoked dysesthesiae with local anesthesia

Pain reduces itch - a commonly known effect of scratching the skin. Experimentally produced itch from histamine is sometimes accompanied by secondary sensations of pain. The present study investigated the effects of eliminating this pain, by means of a local anesthetic, on the itch and the enhanced mechanically evoked itch and pain that occur after an intradermal injection of histamine. In ten human subjects, the volar forearm was injected with either 20 mul of 2% chloroprocaine (experimental arm), or 20 mul of saline (control arm). Histamine 10 mul was injected into each bleb, and the resulting magnitude of itch estimated. The borders of three cutaneous areas were mapped within which mechanical stimulation of the skin surrounding the bleb elicited abnormal sensations (dysesthesiae): alloknesis, defined as itch evoked by innocuous stroking, and hyperalgesia and hyperknesis, characterized, respectively, by enhanced pain and enhanced itch evoked by pricking the skin with a fine tipped filament. The magnitude and duration of itch were significantly greater and the areas of dysesthesia significantly larger for the experimental than for the control arm. It is hypothesized that there exist two classes of histamine-sensitive primary afferent neurons. One class is 'pruritic', and mediates itch whereas the other is 'antipruritic', and evokes a centrally mediated reduction in histamine-evoked itch and dysesthesiae. It is further suggested that the anesthetic blocked the discharges of the antipruritic afferents, preventing the central inhibition from occurring and thereby unmasking the effects of the pruritic afferents.     

HD、HD+ HDF及PD对老年尿毒症患者皮肤瘙痒症的疗效比较

目的:对比分析血液透析(HD)、血液透析联合血液透析滤过(HD+HDF)、腹膜透析(PD)三种方式对老年尿毒症患者皮肤瘙痒症的疗效,为老年尿毒症患者皮肤瘙痒症的治疗提供参考。方法:选取2010年3月至2014年3月来我院就诊的老年尿毒症皮肤瘙痒症患者共100例作为研究对象,采用随机数表法随机分为HD组(33例)、联合组(33例)、PD组(34例),在初次透析前后、透析后1个月、透析后2个月记录患者皮肤瘙痒评分,并检测患者全段甲状旁腺激素(i PTH)、β2-微球蛋白(β2-MG)的水平。透析2个月后比较三组对皮肤瘙痒症的疗效。结果:联合组和PD组透析2月后β2-MG水平、i PTH水平、瘙痒症评分明显低于HD组,差异具有统计学意义(P<0.05)。PD组透析2月后β2-MG水平低于联合组,但差异不具有统计学意义(P>0.05)。PD组透析2月后i PTH水平明显低于联合组,差异具有统计学意义(P<0.05)。PD组透析2月后评分明显低于联合组,差异具有统计学意义(P<0.05)。PD组、联合组有效率明显高于HD组,差异具有统计学意义(P<0.05);PD组有效率高于联合组,但差异怒具有统计学意义(P>0.05)。结论 :血液透析联合血液透析滤过与腹膜透析均可以明显降低患者全段甲状旁腺激素、β2-微球蛋白的水平,缓解患者瘙痒症状,提升患者生活质量,值得临床推广。     

Parasitic mites of medical and veterinary importance – is there a common research agenda?

There are an estimated 0.5–1 million mite species on earth. Among the many mites that are known to affect humans and animals, only a subset are parasitic but these can cause significant disease. We aim here to provide an overview of the most recent work in this field in order to identify common biological features of these parasites and to inform common strategies for future research. There is a critical need for diagnostic tools to allow for better surveillance and for drugs tailored specifically to the respective parasites. Multi-‘omics’ approaches represent a logical and timely strategy to identify the appropriate mite molecules. Recent advances in sequencing technology enable us to generate de novo genome sequence data, even from limited DNA resources. Consequently, the field of mite genomics has recently emerged and will now rapidly expand, which is a particular advantage for parasitic mites that cannot be cultured in vitro. Investigations of the microbiota associated with mites will elucidate the link between parasites and pathogens, and define the role of the mite in transmission and pathogenesis. The databases generated will provide the crucial knowledge essential to design novel diagnostic tools, control measures, prophylaxes, drugs and immunotherapies against the mites and associated secondary infections.     

Sex-related differences in SLIGRL-induced pruritus in mice

Aims

Pruritus is a common symptom of skin diseases, and is associated with impaired sleep quality and a considerable reduction in the patient's quality of life. Recently, it was reported that there are sex-specific differences in scratching behavior in chronic pruritus patients. Namely, female chronic pruritus patients scratch more and have significantly more scratch lesions than male patients. However, few animal studies have examined sex-related differences in scratching behavior. Thus, the present work investigated sex-related differences in animal pruritus using pruritogens, which are often used to create experimental animal models of itching.

Main methods

Acute pruritus was induced in ICR mice by a single intradermal injection of histamine, 4-methylhistamine, serotonin, compound 48/80, substance P (SP), or the proteinase-activated receptor-2 (PAR-2)-activating peptide SLIGRL-NH₂. Chronic pruritus was induced by 5 weeks of the repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB) to BALB/c mice.

Key findings

Female mice showed significantly higher scratching counts in SLIGRL-NH₂-induced pruritus than male mice. Conversely, there was no obvious sex-related difference in scratching behavior for the other pruritogens examined.

Significance

These results indicate that sex-related differences may exist in the pruritogen-responsive neurons that transmit the itch signal induced by SLIGRL-NH₂, but not by histamine or 5-HT.