Publications (10)24.16 Total impact
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Article: Ineffective topical treatment of vitiligo with Cucumis melo extracts.
International journal of dermatology 03/2011; 50(3):374-5. · 1.18 Impact Factor -
Article: Significant immediate and long-term improvement in quality of life and disease coping in patients with vitiligo after group climatotherapy at the Dead Sea.
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ABSTRACT: Quality of life in patients with vitiligo is impaired. This study explored the immediate effect of 20 days of climatotherapy at the Dead Sea on quality of life, coping with the disease, general well-being and individual stress levels in a group of 71 patients with vitiligo and 42 matched controls. The long-term effect was assessed after 12 months in 33/71 patients and 12/42 controls. Study instruments were Dermatology Life Quality Index, Beck Depression Inventory and the Adjustment to Chronic Skin Disorders Questionnaire. Stress measurements were based on cortisol and β-endorphin concentrations in saliva samples. Quality of life was significantly improved at day 20 at the Dead Sea compared with day 1, and this was still significant after 12 months. Moreover, social anxiety/avoidance, anxious-depressive mood and helplessness as measured by the Adjustment to Chronic Skin Disorders Questionnaire were significantly reduced. There was no difference in levels of cortisol and β-endorphin between patients and controls, indicating that stress per se is not a significant contributor in vitiligo. In conclusion, therapy in patient groups offers an effective tool for long-lasting improvement in quality of life and patients' well-being.Acta Dermato-Venereologica 01/2011; 91(2):152-9. -
Article: From basic research to the bedside: efficacy of topical treatment with pseudocatalase PC-KUS in 71 children with vitiligo.
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ABSTRACT: The epidermal accumulation of hydrogen peroxide (H(2)O(2)) has been documented in vitiligo. To assess the effect on disease cessation and repigmentation of the reduction/removal of H(2)O(2) using low-dose, narrow-band, ultraviolet-B (UV-B)-activated pseudocatalase PC-KUS in 71 children with vitiligo. This uncontrolled and retrospective study included 45 girls and 26 boys (mean age, 10.3 years) who applied topical PC-KUS twice daily to the entire body surface without narrow-band UV-B dose increments. The affected body areas were documented by special photography at the first visit and after 8-12 months. The response was evaluated by two independent physicians as > 75% vs. < 75% total repigmentation of the face/neck, trunk, extremities, and hands/feet. Generalized (n = 61) and segmental (n = 10) vitiligo were evaluated as different entities. The effect of total-body, low-dose, narrow-band UV-B (0.15 mJ/cm(2)) monotherapy once daily without any increments and without application of PC-KUS was tested over 6 months in 10 children with vitiligo vulgaris (mean age, 8.4 years). One hundred per cent cessation was observed in 70 of the 71 children. More than 75% repigmentation was achieved in 66 of 71 patients on the face/neck, 48 of 61 on the trunk, and 40 of 55 on the extremities; however, repigmentation on the hands/feet was disappointing (five of 53). The response was independent of skin color, age of onset, duration of disease, other demographic features, and previous treatments. The follow-up after narrow-band UV-B monotherapy showed no significant repigmentation in all areas. Seven of 10 patients showed progression of their vitiligo. A reduction in epidermal H(2)O(2) using low-dose, narrow-band UV-B-activated pseudocatalase PC-KUS is an effective treatment for childhood vitiligo which can be safely performed at home.International journal of dermatology 07/2008; 47(7):743-53. · 1.18 Impact Factor -
Article: Basic research confirms coexistence of acquired Blaschkolinear Vitiligo and acrofacial Vitiligo.
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ABSTRACT: We report about a female patient with bilateral and unilateral blaschkolinear depigmentation on the extremities and coexistence of acrofacial vitiligo, who initially presented her first signs of depigmentation at the age of 32 years. The patient was otherwise healthy. The correct diagnosis was based on the latest up to date technology utilizing in vivo FT-Raman and Fluorescence spectroscopy, Wood's light examination of the depigmented skin and immunoreactivity of epidermal catalase expression in 3 mm punch biopsies from the linear depigmented area. The results yielded decreased catalase protein expression compared to healthy controls as well as complete absence of melanocytes. FT-Raman spectroscopy identified the presence of hydrogen peroxide (H(2)O(2)) in the mM range and Fluorescence spectroscopy demonstrated H(2)O(2)-mediated oxidation of tryptophan residues in the depigmented area. The results were in agreement with vitiligo. Repigmentation of the linear lesion was initiated after reduction/removal of epidermal H(2)O(2) with pseudocatalase PC-KUS further supporting the correct diagnosis. To the best of our knowledge this is the first case documented with vitiligo following Blaschko lines in coexistence with classical acrofacial vitiligo. This observation raises the question whether besides H(2)O(2)-mediated stress in association with genomic mosaicism could play a role in some cases with vitiligo.Archives for Dermatological Research 08/2007; 299(5-6):225-30. · 2.28 Impact Factor -
Article: Estrogens can contribute to hydrogen peroxide generation and quinone-mediated DNA damage in peripheral blood lymphocytes from patients with vitiligo.
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ABSTRACT: To date there is ample in vivo and in vitro evidence for increased epidermal and systemic hydrogen peroxide (H(2)O(2)) levels in vitiligo, which can be reduced with a topical application of a pseudocatalase-K.U. Schallreuter (PC-KUS) leading to the recovery of epidermal catalase levels as well as other enzymes in peripheral blood cells. Recently, the generation of H(2)O(2) by oxidative metabolism of estrogens and other aromatic steroids was documented. Therefore, it was tempting to follow estrogen-generated H(2)O(2) and its possible effect on DNA damage in peripheral blood lymphocytes from patients with vitiligo before and after the reduction of epidermal H(2)O(2) with pseudocatalase PC-KUS compared to controls. For this purpose, 20 Caucasian patients were grouped in treated responders (group A, n=11) and untreated active/acute disease (group B, n=9) and compared to Caucasian healthy controls (group C, n=7). Consequently, epidermal catalase protein expression in full skin biopsies was assessed using immunofluorescence labelling together with determination of basal H(2)O(2) levels in peripheral blood lymphocytes. To test the influence of estrogen on H(2)O(2) generation and DNA damage, freshly prepared peripheral blood lymphocytes from all three groups were used for the alkaline comet assay in the presence and absence of catalase. The results of this study demonstrated that reduction of epidermal H(2)O(2) leads to both increased epidermal catalase protein expression as well as decreased H(2)O(2) concentrations in lymphocytes. Moreover, a direct estrogen-mediated DNA damage was identified in both patient groups, which was absent in healthy controls. This effect was not abolished by catalase pointing to direct quinone-mediated DNA damage by estrogens in peripheral blood lymphocytes in vitiligo.Journal of Investigative Dermatology 06/2006; 126(5):1036-42. · 6.31 Impact Factor -
Article: Decreased phenylalanine uptake and turnover in patients with vitiligo.
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ABSTRACT: The human epidermis has the full machinery for autocrine L-phenylalanine turnover to L-tyrosine in keratinocytes and melanocytes. Phenylalanine hydroxylase (PAH) activities increase linearly with inherited skin colour (skin phototype I-VI, Fitzpatrick classification) yielding eightfold more activities in black skin compared to white skin. Moreover, UVB irradiation (1 MED) significantly increases epidermal PAH activities 24 h after exposure. Importantly, L-phenylalanine uptake and turnover in the pigment forming melanocytes is vital for initiation of melanogenesis. In this context it was shown that the uptake of this amino acid is regulated by calcium. The depigmentation disorder vitiligo provides a unique model to follow impaired L-phenylalanine turnover in the skin as well as in serum because affected individuals hold an impaired epidermal 6BH4 de novo synthesis/recycling and regulation including low epidermal PAH activities. After overnight fasting and oral loading with L-phenylalanine (100 mg/kg body weight), 29.6% of 970 patients tested (n=287/970) yielded serum phenylalanine/tyrosine ratios >or=4 and 35.3% (n=342/970) had mild to moderate hyperphenylalaninaemia (HPA), while 9.3% (n=90/970) had both serum L-phenylalanine levels >or=2.0 mg/dl and phe/tyr ratios >or=4.0. Isolated HPA was found in 26% (n=252/970), whereas 20.3% had only increased ratios (n=197/970). None of the patients had phenylketonuria and the family history for this metabolic disease was negative. The IQ followed normal Gaussian distribution. In vitro L-phenylalanine uptake/turnover studies on primary epidermal melanocytes originating from these patients demonstrated a significantly decreased calcium dependent L-phenylalanine uptake and turnover compared to healthy control cells. Based on our observation, we would like to propose that phenylalanine uptake/turnover is under tight control by calcium which in turn could offer an additional novel mechanism in the aetiology of HPA.Molecular Genetics and Metabolism 01/2006; 86 Suppl 1:S27-33. · 3.19 Impact Factor -
Article: Rapid initiation of repigmentation in vitiligo with Dead Sea climatotherapy in combination with pseudocatalase (PC-KUS).
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ABSTRACT: Low catalase levels and cellular vacuolation in the epidermis of patients with vitiligo support major oxidative stress in this compartment. There is now in vivo evidence for increased epidermal hydrogen peroxide (H(2)O(2)) accumulation in this patient group by utilizing noninvasive Fourier Transform Raman spectroscopy (FT Raman). Epidermal H(2)O(2) can be removed with a topical application of narrow band UVB activated pseudocatalase cream (PC-KUS). (Mn/EDTA-bicarbonate complex, patent No. EPO 58471 1 A), yielding initiation of repigmentation. Dead Sea climatotherapy is another successful treatment modality for vitiligo, but the mode of action has escaped definition so far. Epidermal hydrogen peroxide (H(2)O(2)) was assessed in vivo before and after 21 days treatment at the Dead Sea using noninvasive Fourier-Transform Raman spectroscopy. The effectiveness of repigmentation was followed in 59 patients with vitiligo by comparing Dead Sea climatotherapy alone with the combination of Dead Sea climatotherapy/pseudocatalase cream (PC-KUS) as well as Dead Sea climatotherapy/placebo cream. Clinical repigmentation was documented by standardized black/white photography using non-UV coated bulbs as flashlight and by color photography. This study on 59 patients who had vitiligo for an average time of 17 years (range 3-53 years) confirmed in vivo H(2)O(2) accumulation in mM concentrations in the epidermis of untreated patients. Furthermore, we demonstrated a pseudocatalase activity after 15 min of Dead Sea bathing, but the decrease of epidermal H(2)O(2) levels was significantly less compared to narrowband UVB activated pseudocatalase cream (PC-KUS). Initiation of repigmentation was already observed between day 10 and day 16 after a combination of Dead Sea climatotherapy/pseudocatalase cream compared to conventional pseudocatalase monotherapy (8-14 weeks) and Dead Sea climatotherapy alone (5-6 weeks). 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.International Journal of Dermatology 09/2002; 41(8):482-7. · 1.14 Impact Factor -
Article: In vitro and in vivo identification of ‘pseudocatalase’ activity in Dead Sea water using Fourier transform Raman spectroscopy
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ABSTRACT: Balneotherapy with Dead Sea water has been reported as a successful treatment modality for psoriasis, atopic eczema and vitiligo, but the precise mode of action has escaped definition so far. The saturating salt concentration (346 g/litre) together with the unique UV spectrum have been suggested to trigger the release of pro-inflammatory and chemotactic mediators. The results of our study show for the first time a high content of transition metal ions (manganese, iron and copper) in Dead Sea water. Using in vitro Fourier transform (FT) Raman spectroscopy, we were able to identify ‘pseudocatalase’ activity by observing the decomposition of hydrogen peroxide (H2O2) over time by Dead Sea water. Since patients with vitiligo accumulate millimolar levels of H2O2 in their skin, we followed the degradation of H2O2in vivo again utilizing the same technique. The results of this in vitro and in vivo study show for the first time a ‘pseudocatalase’ activity of Dead Sea water and provide evidence that the antioxidant properties of Dead Sea water bathing could play an important role in this unique treatment modality. Furthermore, the use of non-invasive in vivo FT-Raman spectroscopy introduces an excellent biomedical application in investigative dermatology. Copyright © 2002 John Wiley & Sons, Ltd.Journal of Raman Spectroscopy 07/2002; 33(7):586 - 592. · 3.09 Impact Factor -
Article: Decreased photodamage and low incidence of non-melanoma skin cancer in 136 sun-exposed caucasian patients with vitiligo.
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ABSTRACT: It is well established that ultraviolet radiation is related to non-melanoma skin cancer (NMSC) in Caucasians. Considering that patients with vitiligo have often no protective pigment in sun-exposed depigmented/white skin together with severe oxidative stress due to accumulation of millimolar epidermal hydrogen peroxide (H(2)O(2)), it would be expected that these patients develop a higher risk for early photodamage and NMSC. However, scattered reports on low patient numbers documented no increased risk for sun-induced skin cancers in this disease. The aim of this study was to validate the possible photodamage and the development of epidermal neoplasia in a randomly selected larger patient group with emphasis on each patient's sun sensitivity and the history of solar habits. Furthermore we wished to compare histological signs for epidermal photodamage in a random representative patient group (mean age >30 years) and age-matched healthy controls. One hundred and thirty-six randomly selected patients (females n = 93; males n = 43; mean age 42.4 years, range 14-70 years) were included in this study. To assess signs of photodamage and skin cancer, all patients underwent a thorough full-body examination by Wood's light and dermatoscopy. In order to learn about each patient's individual sun sensitivity and solar habits, a direct questionnaire was used. In addition full skin punch biopsies of sun-exposed depigmented/pigmented skin were taken under local anaesthesia and evaluated by light microscopy. There was no evidence for sun-related damage in the entire patient group, despite a significant number of positive cases with a history of sunburns in early childhood and continuous accumulation of epidermal H(2)O(2). Histological examination of the epidermis showed no signs of increased photo-ageing and confirmed the absence of apoptosis in these patients. Furthermore surprisingly there was no increased risk for photosensitivity disorders, i.e. polymorphous light reaction, solar urticaria and acute actinic dermatitis. The results of this study confirm in a large group of patients with vitiligo the absence of an expected high risk for sun-induced damage and skin cancer. Based on these results together with a recent report on increased functional wild-type p53 expression in these patients we would like to propose that in vitiligo there may be a direct association between this important tumour suppressor and the absence of photodamage and NMSC.Dermatology 01/2002; 204(3):194-201. · 2.05 Impact Factor -
Article: In Vivo and In Vitro Evidence for Hydrogen Peroxide (H2O2) Accumulation in the Epidermis of Patients with Vitiligo and its Successful Removal by a UVB-Activated Pseudocatalase
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ABSTRACT: 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 IIIEDTA-(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.Keywords: oxidative stress, tetrahydrobiopterin, repigmentationJournal of Investigative Dermatology Symposium Proceedings 08/1999; 4(1):91-96. · 3.73 Impact Factor
Top co-authors
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Institutions
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2006–2008
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University of Bradford
- Bradford School of Medical Sciences
Bradford, ENG, United Kingdom
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1999–2002
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Ernst-Moritz-Arndt-Universität Greifswald
Greifswald, Mecklenburg-Vorpommern, Germany
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