Thioredoxin Reductase Activity in Hermansky-Pudlak Syndrome: A Method for Identification of Putative Heterozygotes

Recent studies indicate that membrane-associated thioredoxin reductase (TR) is a possible regulator of melanin biosynthesis via the inhibition of tyrosinase by reduced thioredoxin. In normal individuals, the levels of TR activity in skin correlate linearly to the Fitzpatrick classification of skin type, being lowest in type I skin and highest in skin type VI. In this study, TR was measured in 3-mm skin biopsies in Hermansky-Pudlak syndrome (HPS) patients and their relatives. Forty-five individuals from seven Puerto Rican kindreds were tested, including 12 homozygotes, nine obligate heterozygotes, and 24 unclassified individuals. In addition, seven separate nonkindred HPS patients were tested. With one exception, TR activity was markedly decreased in 18 homozygotes. TR activity was decreased in eight obligate heterozygotes and in 12 unclassified kindred members, whereas 10 subjects had normal TR activity when compared to the expected activity of their skin type. Four individuals were excluded from the analysis because of inadequate controls for their age group or immunosupressive treatment for kidney transplant. The results indicate that decreased TR activity assayed in 3-mm skin punch biopsies is a useful method for detecting carriers of the HPS gene

Q10-triggered facial vitiligo.

noBackground Generation and accumulation of reactive oxygen/nitrogen species in the epidermis of patients with vitiligo has been widely documented. Moreover, semiquinone radical-mediated sensitivity has been shown in blood lymphocytes of these patients. Objectives To determine the possible mechanism behind Q10-induced facial vitiligo. Methods This was a clinical assessment supported by in vivo Fourier transform–Raman spectroscopy and repigmentation. Results Topical Q10 application generated hydrogen peroxide (H2O2) leading in turn to facial vitiligo in susceptible individuals. Proof of the basic result stemmed from reduction of epidermal H2O2 by using narrowband ultraviolet B-activated propseudocatalase PC-KUS in association with cessation of depigmentation and repigmentation of the lost skin colour. Conclusions Over-the-counter availability of Q10-containing topical formulations can be harmful to individuals susceptible to vitiligo

Cumulative life course impairment in vitiligo.

noVitiligo is an acquired, idiopathic skin disease characterized by the mostly progressive loss of the inherited skin color leading to white patches and in some cases to total depigmentation. The course of this ancient disease is still unknown. The worldwide prevalence range is 0.5-1%. The disease burden includes stigmatization, depression, impaired quality of life, lack of self-confidence, embarrassment and self-consciousness. To the best of our knowledge, the extent to which this chronic disease may exert an influence upon the life course of affected individuals has, to date, not been investigated. The material presented herein is the result of an accurate analysis of published literature. Moreover, we included our own data collected in two studies. To apply the concept of cumulative life course impairment in vitiligo, we looked at possible trigger factors, role of patient's age and the age at disease onset, disease duration and stigmatization. Stigmatization had the strongest impact. It is common in patients with an early disease onset, often leading to other disturbances. Our data revealed that older patients or those with a disease onset later in life adjust better to this chronic skin disorder and that they are less socially avoidant. However, long disease duration can also lead to impaired quality of life and obsession, while this group seems to be less depressed or embarrassed. Results from our own work with peer groups of these patients strongly support a positive long-lasting effect of treatment on quality of life of children, adolescents and adults. To which extent vitiligo may contribute to a cumulative life course impairment remains to be shown

Modelling the hair follicle dermal papilla using spheroid cell cultures.

noVitiligo occurs in Northern Europe in one of 200 people. The disease can cause significant psychological stress for the affected individual. These patients generate and accumulate massive amounts of H2O2- and peroxynitrite in the epidermal compartment. Consequently many proteins are oxidized or nitrated, leading in turn to partial or complete loss of functionality. Moreover, presence of DNA damage in the skin as well as in plasma has been shown, while apoptosis is not enhanced. Induction of DNA repair is associated with up-regulated functioning p53 protein. Considering possible genetic predisposition and /or spontaneous mutations, autoimmune reactions in the disease are put forward in the context of oxidative stress. In addition a review of recent and novel treatment modalities including the role of oxidative stress reduction and combined climatotherapy at the Dead Sea in a group are discussed