To date there is compelling in vitro and in vivo evidence for epidermal H2O2 accumulation in vitiligo. This paper reviews the literature and presents new data on oxidative stress in the epidermal compartment of this disorder. Elevated H2O2 levels can be demonstrated in vivo in patients compared with healthy controls by utilizing Fourier-Transform Raman spectroscopy. H2O2 accumulation is associated with low epidermal catalase levels. So far, four potential sources for epidermal H2O2 generation in vitiligo have been identified: (i) perturbed (6R)-L-erythro 5,6,7,8 tetrahydrobiopterin (6BH4) de novo synthesis/recycling/regulation; (ii) impaired catecholamine synthesis with increased monoamine oxidase A activities; (iii) low glutathione peroxidase activities; and (iv) "oxygen burst" via NADPH oxidase from a cellular infiltrate. H2O2 overproduction can cause inactivation of catalase as well as vacuolation in epidermal melanocytes and keratinocytes. Vacuolation was also observed in vitro in melanocytes established from lesional and nonlesional epidermis of patients (n = 10) but was reversible upon addition of catalase. H2O2 can directly oxidize 6BH4 to 6-biopterin, which is cytotoxic to melanocytes in vitro. Therefore, we substituted the impaired catalase with a "pseudocatalase". Pseudocatalase is a bis-manganese III-EDTA-(HCO3-)2 complex activated by UVB or natural sun. This complex has been used in a pilot study on 33 patients, showing remarkable repigmentation even in long lasting disease. Currently this approach is under worldwide clinical investigation in an open trial. In conclusion, there are several lines of evidence that the entire epidermis of patients with vitiligo is involved in the disease process and that correction of the epidermal redox status is mandatory for repigmentation.

It has been shown in vivo that patients with the depigmentation disorder vitiligo accumulate hydrogen peroxide (H(2)O(2)) accompanied by low catalase levels and high concentrations of 6- and 7-biopterin in their epidermis. Earlier it was demonstrated that epidermal 4a-OH-tetrahydrobiopterin dehydratase, an important enzyme in the recycling process of 6(R)-L-erythro 5,6,7,8 tetrahydrobiopterin (6BH(4)), has extremely low activities in these patients concomitant with a build-up of the abiogenic 7-isomer (7BH(4)), leading to competitive inhibition of epidermal phenylalanine hydroxylase. A topical substitution for the impaired epidermal catalase with a pseudocatalase effectively removes epidermal H(2)O(2), yielding a recovery of epidermal 4a-OH-tetrahydrobiopterin dehydratase activities and physiologic 7BH(4) levels in association with successful repigmentation demonstrating recovery of the 6BH(4) recycling process. Examination of recombinant enzyme activities, together with 4a-OH-tetrahydrobiopterin dehydratase expression in the epidermis of untreated patients, identifies H(2)O(2)-induced inactivation of this enzyme. These results are in agreement with analysis of genomic DNA from these patients yielding only wild-type sequences for 4a-OH-tetrahydrobiopterin dehydratase and therefore ruling out the previously suspected involvement of this gene. Furthermore, our data show for the first time direct H(2)O(2) inactivation of the important 6BH(4) recycling process. Based on this observation, we suggest that H(2)O(2) derived from various sources could be a general mechanism in the regulation of all 6BH(4)-dependent processes.

Hyperbranched amine polymers (HAS) grown from the mesoporous silica SBA-15 (hereafter "SBA-15-HAS") exhibit large capacities for CO2 adsorption. We have used static in situ and magic-angle spinning (MAS) ex situ (13)C nuclear magnetic resonance (NMR) to examine the adsorption of CO2 by SBA-15-HAS. (13)C NMR distinguishes the signal of gas-phase (13)CO2 from that of the chemisorbed species. HAS polymers possess primary, secondary, and tertiary amines, leading to multiple chemisorption reaction outcomes, including carbamate (RnNCOO(-)), carbamic acid (RnNCOOH), and bicarbonate (HCO3(-)) moieties. Carbamates and bicarbonate fall within a small (13)C chemical shift range (162-166 ppm), and a mixture was observed including carbamic acid and carbamate, the former disappearing upon evacuation of the sample. By examining the (13)C-(14)N dipolar coupling through low-field (B0 = 3 T) (13)C{(1)H} cross-polarization MAS NMR, carbamate is confirmed through splitting of the (13)C resonance. A third species that is either bicarbonate or a second carbamate is evident from bimodal T2 decay times of the ∼163 ppm peak, indicating the presence of two species comprising that single resonance. The mixture of products suggests that (1) the presence of amines and water leads to bicarbonate being present and/or (2) the multiple types of amine sites in HAS permit formation of chemically distinct carbamates.

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The results of this study show a significantly faster initiation of repigmentation in vitiligo after a combination of short-term climatotherapy (21 days) at the Dead Sea in combination with a pseudocatalase cream (PC-KUS) compared to either conventional climatotherapy at the Dead Sea alone or with placebo cream in combination with climatotherapy. This combined therapy is significantly faster in repigmentation than narrowband UVB activated pseudocatalase cream (PC-KUS) treatment alone. The results of this study support the necessity of epidermal H2O2 removal as well as the influence of solar UV-light in the successful treatment of vitiligo.