Melanocyte destruction and repigmentation in vitiligo: A model for nerve cell damage and regrowth

Melanocytes (MCs) are melanin-producing cells of the skin that are derived from neural crest cells. Vitiligo vulgaris is a common depigmentation disorder resulting from the destruction of functional MCs in the affected skin. The three prevailing pathomechanisms of vitiligo are the immune hypothesis, the neural hypothesis and the autocytotoxic hypothesis. None of these mechanisms has been conclusively proven. Melanoblasts (MBs) in the outer root sheath of the hair follicles are the reservoir cells for repigmentation. Recovery from vitiligo is initiated by activation and proliferation of these MBs, followed by upward migration to the nearby epidermis that forms perifollicular pigmentation islands. Migration, proliferation and differentiation of MCs and MBs are regulated by keratinocyte-derived factors and some coat color genes. Any therapy for vitiligo must explain not only the repopulation of MCs but also their functional development. In patients with vitiligo, MCs are destroyed in the skin, the eyes, and possibly the ears. However, the concept of vitiligo as a systemic disease will be clearly established only when the mechanisms involved in vitiligo are identified. Recent advances in the fields of neural crest cell culture and molecular genetics have opened new perspectives in the understanding of vitiligo. Not only will this result in better treatments for vitiligo patients, but possibly will also provide a key to triggering nerve cell regrowth in other nervous diseases.     

自体吸疱表皮移植术结合搔刮术治疗白癜风的临床评价

目的:观察和比较搔刮术结合负压吸疱术和传统负压吸疱术对白癜风复色的疗效。方法:将90例稳定期白癜风患者随机分成搔刮术结合负压吸疱术组(45例)和传统负压吸疱术组(45例),分别给予搔刮术结合负压吸疱术和传统负压吸疱术治疗。治疗后,比较两组的复色情况,是否留有白斑缝隙,并进行白癜风疗效评价。进一步分析皮损部位、性别、临床类型对搔刮术结合负压吸疱术和传统负压吸疱术临床疗效的影响。结果:治疗后,搔刮术结合负压吸疱术组和传统负压吸疱术组在整体疗效无显著性差异(P0.05)。搔刮术结合负压吸疱术组术后获得成片复色比例显著高于传统负压吸疱术组(88.9%vs. 4.4%,P0.001)。不同性别患者接受搔刮术结合负压吸疱术和传统负压吸疱术的疗效比较均无统计学差异(P0.05)。表皮移植术结合搔抓术组和单一表皮移植术组中,皮损发生在颈部、面部相比于躯干部、四肢、手足部的疗效明显更佳,局限型和节段型相比于散发型、肢端型的疗效更佳。结论:自体吸疱表皮移植术结合搔刮术用于稳定期白癜风的复色效果相比于传统自体吸疱表皮移植术疗效更佳。     

白癜风患者求医行为的调查研究

目的:本文的目的是研究白癜风患者的求医行为及男女性别之间的差异,分析患者选择医疗机构的原因并指导他们正确就医.方法:我们对210例白癜风患者进行问卷调查分析.访谈问卷内容包括人口统计学特征、白癜风知识、求医行为及原因、疾病的发展及心理状态的调查等.结果:仅14.3％的患者对自身疾病的基本知识回答正确,并且患者主要通过医生获得疾病知识;81.0％的患者首诊时选择公立综合医院,医疗技术水平(占69.9％)是患者在首诊时选择医疗机构的主要考虑方面,50.5％的患者存在多处求医的现象;81 4％的患者存在不同程度的心理压力.结论:白癜风患者普遍存在多处求医及不良求医行为,公立医院是目前白癜风患者的主要流向;白癜风患者的认知程度、心理状态等不容乐观;我们应针对白癜风患者多次求医和乱求医的行为及其原因开展白癜风健康教育,正规医疗机构应通过改善服务质量、提高疗效、加强宣传等促进白癜风患者正确求医.     

Melanin-concentrating hormone and melanin-concentrating hormone receptors in mammalian skin physiopathology

To date, there is a dearth of evidence to support functions for melanin-concentrating hormone (MCH) and melanin-concentrating hormone receptors (MCH-R) in mammalian skin physiology including pigmentation, inflammation and immune responses and skin cell proliferation. Much research is therefore still needed to define the roles of the hormone and its receptors in mammalian skin. This will be a crucial step to identifying pathogenic mechanisms that may involve the MCH/MCH-R system in the context of inflammatory and autoimmune skin diseases as well as skin cancers. The following review summarizes the studies which have been carried out to examine the expression and function of MCH and MCH-R in mammalian skin. Recent findings with regard to humoral immune responses to the MCH-R1 in patients with the skin depigmenting disease vitiligo are also discussed.     

Synthesis and bioactivity of novel isoxazole chalcone derivatives on tyrosinase and melanin synthesis in murine B16 cells for the treatment of vitiligo

A new series of chalcone derivatives 1–18, bearing isoxazole moieties were designed and synthesized, and biologically evaluated for their activity on mushroom tyrosinase and melanin synthesis in murine B16 cells. The result indicated that most of prepared compounds 1–18 showed potent activating effect on tyrosinase, especially for 1–2, 4, 6–7, 9 and 15. Among them, compounds 2, 4 and 9 demonstrated the best activity with EC₅₀ = 1.3, 2.5 and 3.0 μmol·L⁻¹ respectively, much better than the positive control 8-methoxypsoralan (8-MOP, EC₅₀ = 14.8 μmol·L⁻¹); In B16 cells, all the tested compounds exhibited a stronger activity on melanogenesis than 8-MOP (with the value of 115%). It was interesting that derivatives substituted with halogen (1, 2, 4, 5, 7, 9) were generally more potent. Compounds 2 (463%) and 18 (438%) with 3 and 4-fold potency compared with 8-MOP respectively, were recognized as the most promising candidate hits for further pharmacological study of anti-vitiligo.     

Analysis of allelic variants in the catalase gene in patients with the skin depigmenting disorder vitiligo

Vitiligo is an acquired hypomelanotic skin disorder characterised by circumscribed depigmented macules resulting from the loss of functional melanocytes from the cutaneous epidermis. Conditions that might result in epidermal oxidative stress and consequently damage to pigment cells have been reported in the skin of vitiligo patients, including low catalase activity and increases in hydrogen peroxide levels. However, the cause of the decrease in catalase activity has not been equivocally determined. Several allelic variants in the catalase gene, a number of which have deleterious effects upon the expression or function of the enzyme, have been described and the aim of the present work was to assess the relevance of catalase gene variants in patients with vitiligo. Associations between ten separate allelic variants in the catalase gene and a predisposition to vitiligo were investigated in case-control studies with 166 English patients and 169 ethnically-matched controls using DNA sequencing and restriction fragment length polymorphism-polymerase chain reaction methods. Of the ten allelic variants analysed, only a C/T single nucleotide polymorphism in exon 9 of the catalase gene was associated with vitiligo. The C/T genotype was significantly over-represented in the vitiligo patient group compared with the control cohort. Of 166 vitiligo genotypes, 66 (39.8%) had the C/T variant compared to 45/169 (26.6%) control genotypes (P = 0.030). No evidence for an association between other allelic variants in the catalase gene and vitiligo susceptibility was found. The low catalase activity in vitiligo patient epidermis is more likely to result from environmental conditions such as inhibitory levels of hydrogen peroxide rather than allelic variations in the catalase gene which affect either expression or function of the enzyme.     

Different Populations of Melanocytes Are Present in Hair Follicles and Epidermis

Melanocytes in human skin reside both in the epidermis and in the matrix and outer root sheath of anagen hair follicles. Comparative study of melanocytes in these different locations has been difficult as hair follicle melanocytes could not be cultured. In this study we used a recently described method of growing hair follicle melanocytes to characterize and compare hair follicle and epidermal melanocytes in the scalp of the same individual. Three morphologically and antigenically distinct types of melanocytes were observed in primary culture. These included (1) moderately pigmented and polydendritic melanocytes derived from epidermis; (2) small, bipolar, amelanotic melanocytes; and (3) large, intensely pigmented melanocytes; the latter two were derived from hair follicles. The three sub-populations of cells all reacted with melanocyte-specific monoclonal antibody. Epidermal and amelanotic hair follicle melanocytes proliferated well in culture, whereas the intensely pigmented hair follicle melanocytes did not. Amelanotic hair follicle melanocytes differed from epidermal melanocytes in being less differentiated, and they expressed less mature melanosome antigens. In addition, hair follicle melanocytes expressed some antigens associated with alopecia areata, but not antigens associated with vitiligo, whereas the reverse was true for epidermal melanocytes. Thus, antigenically different populations of melanocytes are present in epidermis and hair follicle. This could account for the preferential destruction of hair follicle melanocytes in alopecia areata and of epidermal melanocytes in vitiligo.     

Synthesis and biological evaluation of furocoumarin derivatives on melanin synthesis in murine B16 cells for the treatment of vitiligo

Furocoumarins, isolated from Psoralen corylifolia L., were found to be the most effective drug in the treatment of vitiligo nowadays. Twenty-five furocoumarin derivatives were thus designed and synthesized in order to improve the melanogenesis in B16 cells for the first time. Among them, twenty-three compounds were more potent than the positive control (8-MOP), the commonly used drug for vitiligo in clinic. Noticeably, compounds 6m (350.5%) and 6p (313.1%) based on the scaffold of 6k (2H-benzofuro[2,3-h]chromen-2-one) were nearly 3-fold stronger than 8-MOP (114.50%). The in vitro melanin synthesis evaluation of these structurally diverse analogues had also led to an outline of structure–activity relationship.     

Polymorphisms in the Melanocortin‐1 Receptor (MC1R) and Agouti Signaling Protein (ASIP) Genes in Korean Vitiligo Patients

We have examined the frequency of SNP polymorphisms within the melanocortin‐1 receptor (MC1R) and agouti signaling protein (ASIP) genes in 114 Korean vitiligo patients and 111 normal controls to assess the association of these loci with vitiligo risk. Using direct sequencing techniques, we found the following five MC1R coding region SNPs: Arg67Gln (G200A), Val92Met (G274A), Ile120Thr (T359C), Arg160Arg (C478A), and Gln163Arg (A488G). Of these, the most common were Val92Met at 14% in patients vs. 9% in controls (P = 0.17) and Gln163Arg at 17% in patients vs. 17% in controls (P = 0.84). Presence of the A allele of Val92Met (G274A) was higher in vitiligo patients {P = 0.12, odds ratio (OR) [95% confidence interval (CI)] = 1.68 (0.86–3.25)}. The other three variants showed a frequency <5% of both patients and controls. The ASIP 3′UTR genotype (g.8818A‐G) was also assessed in the same subjects. The frequency of the G allele of 3′UTR in ASIP was 17% in vitiligo and 12% in controls [P = 0.14, OR (95% CI) = 1.49 (0.87–2.54)]. Carriage of the G allele was higher in vitiligo patients [P = 0.17, OR (95% CI) = 1.50 (0.83–2.72)], and those who also carried MC1R Val92Met were more prone to vitiligo [eight of 111 patients vs. four of 111 in controls, P = 0.14, OR (95% CI) = 2.75 (0.71–8.69)]. None of these associations, however, reached statistical significance.     

他克莫司乳膏联合治疗白癜风的疗效评价

目的:通过比较自体表皮移植术联合他克莫司和传统自体表皮移植术治疗白癜风的疗效,明确他克莫司乳膏对白癜风复色率的影响。方法:回顾性分析自体表皮移植术联合他克莫司和传统自体表皮移植术治疗的稳定期白癜风患者共90例,比较其均匀复色时间和疗效。结果:表皮移植术联合他克莫司组起效时间显著性短于单一表皮移植术组(P<0.05),1月、3月的显效率和痊愈率均明显高于单一表皮移植术组(P<0.05)。单一表皮移植术组颈部的疗效相比于头面部、躯干部、四肢更佳(P<0.05),表皮移植术联合0.1%他克莫司软膏外用治疗(相对于单一表皮移植术)可显著性提高位于四肢的皮损的疗效(P<0.05)。相较于单一表皮移植术而言,表皮移植术联合他克莫司对提高节段型和局限型白癜风疗效显著(P<0.05)。然而,他克莫司联合治疗可提高散发型和肢端型白癜风的疗效,但无统计学意义(P>0.05)。表皮移植术联合他克莫司组和单一表皮移植术组中,男性疗效均高于女性,但无显著性差异(P>0.05)。结论:自体表皮移植术联合0.1%他克莫司软膏治疗白癜风的疗效优于单一自体表皮移植术,他克莫司可有效提高白癜风复色。