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Find video protocols related to scientific articles indexed in Pubmed.
CHILD syndrome with mild skin lesions: histopathologic clues for the diagnosis.
J. Cutan. Pathol.
PUBLISHED: 04-07-2014
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CHILD syndrome is an acronym signifying congenital hemidysplasia with ichthyosiform nevus and limb defects. A 27-year-old woman presented with chronic verrucous and hyperkeratotic skin lesions involving the left genital area, left hand and left foot since childhood. The histopathologic findings were consistent with verruciform xanthoma. In correlation with the clinical picture of a linear lesion, the diagnosis of CHILD nevus was made. Subsequent genetic analysis identified a germline c.324C>T (p.A105V) NSDHL mutation and confirmed a diagnosis of CHILD syndrome. This syndrome can be associated with only minimal clinical symptoms. The anatomical distribution of the lesions, a static clinical course and the typical histopathologic features of a CHILD nevus can serve as the clue to a diagnosis of CHILD syndrome in such cases.
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Luminescent dual sensors reveal extracellular pH-gradients and hypoxia on chronic wounds that disrupt epidermal repair.
Theranostics
PUBLISHED: 01-01-2014
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Wound repair is a quiescent mechanism to restore barriers in multicellular organisms upon injury. In chronic wounds, however, this program prematurely stalls. It is known that patterns of extracellular signals within the wound fluid are crucial to healing. Extracellular pH (pHe) is precisely regulated and potentially important in signaling within wounds due to its diverse cellular effects. Additionally, sufficient oxygenation is a prerequisite for cell proliferation and protein synthesis during tissue repair. It was, however, impossible to study these parameters in vivo due to the lack of imaging tools. Here, we present luminescent biocompatible sensor foils for dual imaging of pHe and oxygenation in vivo. To visualize pHe and oxygen, we used time-domain dual lifetime referencing (tdDLR) and luminescence lifetime imaging (LLI), respectively. With these dual sensors, we discovered centripetally increasing pHe-gradients on human chronic wound surfaces. In a therapeutic approach, we identify pHe-gradients as pivotal governors of cell proliferation and migration, and show that these pHe-gradients disrupt epidermal barrier repair, thus wound closure. Parallel oxygen imaging also revealed marked hypoxia, albeit with no correlating oxygen partial pressure (pO2)-gradient. This highlights the distinct role of pHe-gradients in perturbed healing. We also found that pHe-gradients on chronic wounds of humans are predominantly generated via centrifugally increasing pHe-regulatory Na+/H+-exchanger-1 (NHE1)-expression. We show that the modification of pHe on chronic wound surfaces poses a promising strategy to improve healing. The study has broad implications for cell science where spatial pHe-variations play key roles, e.g. in tumor growth. Furthermore, the novel dual sensors presented herein can be used to visualize pHe and oxygenation in various biomedical fields.
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Black tattoos entail substantial uptake of genotoxicpolycyclic aromatic hydrocarbons (PAH) in human skin and regional lymph nodes.
PLoS ONE
PUBLISHED: 01-01-2014
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Hundreds of millions of people worldwide have tattoos, which predominantly contain black inks consisting of soot products like Carbon Black or polycyclic aromatic hydrocarbons (PAH). We recently found up to 200 ?g/g of PAH in commercial black inks. After skin tattooing, a substantial part of the ink and PAH should be transported to other anatomical sites like the regional lymph nodes. To allow a first estimation of health risk, we aimed to extract and quantify the amount of PAH in black tattooed skin and the regional lymph nodes of pre-existing tattoos. Firstly, we established an extraction method by using HPLC-DAD technology that enables the quantification of PAH concentrations in human tissue. After that, 16 specimens of human tattooed skin and corresponding regional lymph nodes were included in the study. All skin specimen and lymph nodes appeared deep black. The specimens were digested and tested for 20 different PAH at the same time.PAH were found in twelve of the 16 tattooed skin specimens and in eleven regional lymph nodes. The PAH concentration ranged from 0.1-0.6 ?g/cm2 in the tattooed skin and 0.1-11.8 ?g/g in the lymph nodes. Two major conclusions can be drawn from the present results. Firstly, PAH in black inks stay partially in skin or can be found in the regional lymph nodes. Secondly, the major part of tattooed PAH had disappeared from skin or might be found in other organs than skin and lymph nodes. Thus, beside inhalation and ingestion, tattooing has proven to be an additional, direct and effective route of PAH uptake into the human body.
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Contact-free inactivation of Trichophyton rubrum and Microsporum canis by cold atmospheric plasma treatment.
Future Microbiol
PUBLISHED: 09-12-2013
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Cold atmospheric plasma (CAP) has already proven efficient at disinfection of microorganisms including biofilms. The objective of the present study is to assess the efficacy of CAP against the dermatophytes Trichophyton rubrum and Microsporum canis in vitro.
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Randomized placebo-controlled human pilot study of cold atmospheric argon plasma on skin graft donor sites.
Wound Repair Regen
PUBLISHED: 06-02-2013
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Cold atmospheric plasma has already been shown to decrease the bacterial load in chronic wounds. However, until now it is not yet known if plasma treatment can also improve wound healing. We aimed to assess the impact of cold atmospheric argon plasma on the process of donor site healing. Forty patients with skin graft donor sites on the upper leg were enrolled in our study. The wound sites were divided into two equally sized areas that were randomly assigned to receive either plasma treatment or placebo (argon gas) for 2 minutes. Donor site healing was evaluated independently by two blinded dermatologists, who compared the wound areas with regard to reepithelialization, blood crusts, fibrin layers, and wound surroundings. From the second treatment day onwards, donor site wound areas treated with plasma (n?=?34) showed significantly improved healing compared with placebo-treated areas (day 1, p?=?0.25; day 2, p?=?0.011; day 3, p?
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Adverse reactions after tattooing: review of the literature and comparison to results of a survey.
Dermatology (Basel)
PUBLISHED: 05-14-2013
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The number of tattooed people has substantially increased in the past years. Surveys in different countries reveal this to be up to 24% of the population. The number of reported adverse reactions after tattooing has also increased including infections, granulomatous and allergic reactions and tumors. However, the case reports do not reflect the frequency of adverse reactions. This review compares the medically documented adverse reactions published in 1991-2011 with the findings of a nation-wide survey that recently revealed the features and health problems associated with tattoos. To compare the data with the survey, the sex of patients was reported and the location and color of tattoos were evaluated. The results show clearly that colored tattoo inks are mainly responsible for adverse skin reactions and that tattoos on the extremities are involved most.
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Evidence-based topical management of chronic wounds according to the T.I.M.E. principle.
J Dtsch Dermatol Ges
PUBLISHED: 04-24-2013
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The number of patients suffering from chronic wound healing disorders in Germany alone is estimated to be 2.5-4 million. Therapy related expenses reach 5-8 billion Euros annually. This number is partially caused by costly dressing changes due to non-standardized approaches and the application of non-evidence-based topical wound therapies. The purpose of this paper is to elucidate a straightforward principle for the management of chronic wounds, and to review the available evidence for the particular therapy options. The T.I.M.E.-principle (Tissue management, Inflammation and infection control, Moisture balance, Epithelial [edge] advancement) was chosen as a systematic strategy for wound bed preparation. Literature was retrieved from the PubMed and Cochrane Library databases and subjected to selective analysis. Topical wound management should be carried out according to a standardized principle and should further be synchronized to the phases of wound healing. Despite the broad implementation of these products in clinical practice, often no benefit exists in the rate of healing, when evaluated in meta-analyses or systematic reviews. This insufficient evidence is additionally limited by varying study designs. In case of non-superiority, the results suggest to prefer relatively inexpensive wound dressings over expensive alternatives. Arbitrary endpoints to prove the effectiveness of wound dressings, contribute to the random use of such therapies. Defining rational endpoints for future studies as well as the deployment of structured therapy strategies will be essential for the economical and evidence-based management of chronic wounds.
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An Internet-based survey on characteristics of laser tattoo removal and associated side effects.
Lasers Med Sci
PUBLISHED: 04-16-2013
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Tattoo removal by laser therapy is a frequently performed procedure in dermatological practices. Quality-switched ruby, alexandrite, or Nd:YAG lasers are the most suitable treatment devices. Although these techniques are regarded as safe, both temporary and permanent side effects might occur. Little has been published on the frequency of complications associated with laser tattoo removal. We performed an Internet survey in German-speaking countries on characteristics of laser tattoo removal and associated side effects. A total number of 157 questionnaires entered the final analysis. Motivations for laser tattoo removal were mainly considering the tattoo as youthful folly (29 %), esthetic reasons (28 %), and 6 % indicated medical problems. One third of participants were unsatisfied with the result of laser tattoo removal, and a complete removal of the tattoo pigment was obtained in 38 % only. Local transient side effects occurred in nearly all participants, but an important rate of slightly visible scars (24 %) or even important scarring (8 %) was reported. Every fourth participant described mild or intense tan when the laser treatment was performed, and the same number of people indicated UV exposure following laser therapy, which should normally be avoided in these circumstances. As reported in the literature, nearly half of the participants experienced hypopigmentation in the treated area. Our results show that from the patients point of view there is an important rate of side effects occurring after laser tattoo removal. Appropriate pretreatment counseling with regard to realistic expectations, possible side effects, and the application of test spots is mandatory to ensure patient satisfaction. Laser treatment should be performed by appropriately trained personnel only.
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Diet-induced pigmented purpuric dermatosis.
Australas. J. Dermatol.
PUBLISHED: 04-10-2013
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Pigmented purpuric dermatoses (PPD) are chronic and relapsing disorders characterised by a localised or generalised purpuric rash. Even though the clinical presentation of PPD subtypes varies, they have a similar histopathology. The aetiology is largely unknown, but trigger factors, such as drugs, infections and systemic illnesses have been described. To our knowledge, this is the only case showing widespread PPD lesions not only induced but also rapidly provoked by dietary factors, namely Coca Cola and apple-cherry fruit spritzer.
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A randomized controlled trial to optimize indocyanine green-augmented diode laser therapy of capillary malformations.
Lasers Surg Med
PUBLISHED: 03-15-2013
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Indocyanine green (ICG)-augmented diode laser therapy (ICG?+?DL) represents a new treatment modality for capillary malformations (CM). However, an increase of the ICG-concentration or the use of an intense pulsed light (IPL) device as light source may further optimize treatment outcomes in CM.
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Phacomatosis pigmentokeratotica is caused by a postzygotic HRAS mutation in a multipotent progenitor cell.
J. Invest. Dermatol.
PUBLISHED: 01-21-2013
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Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus syndrome characterized by the co-occurrence of a sebaceous nevus and a speckled lentiginous nevus. The coexistence of an epidermal and a melanocytic nevus has been explained by two homozygous recessive mutations, according to the twin spot hypothesis, of which PPK has become a putative paradigm in humans. However, the underlying gene mutations remained unknown. Multiple tissues of six patients with PPK were analyzed for the presence of RAS, FGFR3, PIK3CA, and BRAF mutations using SNaPshot assays and Sanger sequencing. We identified a heterozygous HRAS c.37G>C (p.Gly13Arg) mutation in four patients and a heterozygous HRAS c.182A>G (p.Gln61Arg) mutation in two patients. In each case, the mutations were present in both the sebaceous and the melanocytic nevus. In the latter lesion, melanocytes were identified to carry the HRAS mutation. Analysis of various nonlesional tissues showed a wild-type sequence of HRAS, consistent with mosaicism. Our data provide no genetic evidence for the previously proposed twin spot hypothesis. In contrast, PPK is best explained by a postzygotic-activating HRAS mutation in a multipotent progenitor cell that gives rise to both a sebaceous and a melanocytic nevus. Therefore, PPK is a mosaic RASopathy.
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Treatment of leg veins with indocyanine green and lasers investigated with mathematical modelling.
Int J Hyperthermia
PUBLISHED: 11-22-2011
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The treatment of leg veins is routinely performed in clinical practice using near infrared (NIR) lasers. However, due to low absorption of NIR light in blood vessels, the clinical results are still suboptimal. The absorption of the NIR light can be significantly increased with intravenous introduction of an indocyanine green (ICG) dye. In this work a mathematical model was used to delineate clinically valid settings for ICG and NIR lasers for the treatment of leg veins.
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Laser thermal therapy of benign skin tumours: review and update.
Int J Hyperthermia
PUBLISHED: 10-03-2011
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The goal of this review is to provide an overview on laser treatment of benign skin tumours and recent developments in this field. Ablational laser systems are established treatment devices for benign skin tumours. They obtain good cosmetic results with mostly minimal side-effects. Recently, fractional laser devices or combination of laser therapy with photodynamic therapy has gained attention in this field. However, there is a lack of randomised, controlled trials for laser treatment of benign skin tumours.
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Kyrle disease and acquired perforating collagenosis secondary to chronic renal failure and diabetes mellitus.
Case Rep Dermatol
PUBLISHED: 09-29-2011
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A 59-year-old man with chronic renal failure and diabetes mellitus presented with pruritic crusted lesions which histologically were perforating disorders, showing features of both Kyrle disease and acquired perforating collagenosis. The mechanisms of transepidermal elimination and the classification of perforating disorders are briefly discussed. Additionally, we question the concept of perforation, as epidermal damage and exposure of subepidermal substances may artificially present as perforation.
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Whole-body UVB irradiation during allogeneic hematopoietic cell transplantation is safe and decreases acute graft-versus-host disease.
J. Invest. Dermatol.
PUBLISHED: 08-18-2011
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Depletion of host Langerhans cells (LCs) prevents cutaneous graft-versus-host disease (GvHD) in mice. We analyzed whether UVB irradiation is tolerated during the course of human allogeneic hematopoietic cell transplantation and whether depletion of LCs by broadband UVB could improve GvHD outcome. A total of 17 patients received six whole-body UVB irradiations with 75% of the individually determined minimal erythemal dose after conditioning with a reduced intensity protocol. LCs, dermal dendritic cells (DCs), and macrophages were analyzed before and after UVB irradiation by immunohistochemical analysis. Circulating blood cells and serum factors were analyzed in parallel. In striking contrast to previous data, our irradiation protocol was well tolerated in all patients. UVB treatment decreased the number of LCs and also affected dermal DCs. UVB-treated patients also had significantly higher 25-hydroxyvitamin D3 serum levels and higher numbers of circulating CD4+ FoxP3+ regulatory T cells. Strikingly, nine out of nine patients with complete LC depletion (<1 LC per field) developed only grade I GvHD or no GvHD up to day 100. Our results strongly suggest that prophylactic UVB irradiation post transplant is safe and should be further explored as a clinical strategy to prevent acute (skin) GvHD.
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Dermatitis herpetiformis presenting as digital petechiae.
Pediatr Dermatol
PUBLISHED: 08-16-2011
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We present a 15-year-old female patient with a 6-month history of recurrent painful petechiae on the fingers and feet. Trauma or pressure were denied, but she reported recurrent tonsillitis and urinary tract infections and a single event of bilateral scotoma. Extensive investigations (e.g., echocardiography) for a suspected diagnosis of septic emboli were unremarkable. Routine histopathology, direct and indirect immunofluorescence, and esophagogastroduodenoscopy led to the diagnosis of dermatitis herpetiformis. The therapeutic strategy comprised gluten-free diet and dapsone to alleviate the symptoms. Dermatitis herpetiformis should be included in the differential diagnosis of palmar or plantar petechiae, especially when occurring in children or young adults.
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Low incidence of EGFR and HRAS mutations in cutaneous squamous cell carcinomas of a German cohort.
Exp. Dermatol.
PUBLISHED: 07-19-2011
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Epidermal growth factor receptor (EGFR) is highly expressed in squamous cell carcinoma (SCC). The response of patients with lung cancer to EGFR inhibitors is significantly associated with the presence of EGFR mutations. Although these drugs have already been used for the treatment of advanced cutaneous SCC, the knowledge about EGFR mutations in this cancer is limited to one previous study in the US population. We analysed the presence of EGFR and concomitant HRAS mutations in a German cohort of 31 patients with cutaneous SCC by direct sequencing of EGFR and SNaPshot analysis of concomitant RAS mutations. We found a low prevalence of EGFR mutations (1/31; 3%) and HRAS mutations (1/31; 3%). The detected P741L EGFR mutation was proven to be somatic. Our results indicate that both EGFR and HRAS mutations are rare events in the carcinogenesis of cutaneous SCC, and therefore, only a small subgroup of patients will benefit from the screening for EGFR mutations in the run-up to targeted therapies with EGFR inhibitors.
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Black tattoo inks are a source of problematic substances such as dibutyl phthalate.
Contact Derm.
PUBLISHED: 07-03-2011
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Tattooing has recently become increasingly popular. Using tiny needles, tattooists place the tattoo ink in the dermis along with numerous unknown ingredients. Most tattoos consist of black inks, which are predominantly composed of soot products (carbon black with polycyclic aromatic hydrocarbons).
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Skin alterations due to illegal drug abuse.
J Dtsch Dermatol Ges
PUBLISHED: 05-25-2011
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Drug abuse is associated with a wide variety of skin alterations. Being aware of the typical signs and symptoms of the drug addicts skin is of special importance to dermatologists, even though dermatologists are commonly not involved in the treatment of these patients. There is yet a chance for dermatologists to identify drug abusers early by to some extent specific cutaneous signs and after exclusion of several other etiological factors, so that this will lead to further treatment through the respective specialists. The objective of this paper is to draw particular attention to typical skin lesions and diseases which may be associated with drug abuse.
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2D luminescence imaging of physiological wound oxygenation.
Exp. Dermatol.
PUBLISHED: 03-28-2011
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In cutaneous wound healing, the role of oxygen in vivo is poorly understood. We studied wound surface pO(2) during physiological wound healing in humans. Split-thickness skin graft donor sites (n=12) served as standardized wound models. Wound surface pO(2) was measured at 1, 6 and 14days after split-skin harvesting using two-dimensional luminescence lifetime imaging (2D-LLI) of palladium(II)-meso-tetraphenyl-tetrabenzoporphyrin (Pd-TPTBP) in polystyrene-co-acrylonitrile (PSAN) particles on transparent foils. In another experiment, we removed the stratum corneum (SC) on the volar forearm (n=10) by tape strippings to study the impact of the SC on the epidermal oxygen barrier. Split-skin donor site pO(2) significantly decreased during the time course of physiological healing. Regional differences in pO(2) within donor site wounds were visualized for the first time in literature. No difference was found in pO(2) before and after SC removal, showing that the SC is not a major constituent of the epidermal oxygen barrier.
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A rare allergy to a polyether dental impression material.
Clin Oral Investig
PUBLISHED: 03-17-2011
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Polyether impression materials have been used in dentistry for more than 40 years. Allergic reactions to these materials such as reported in the 1970s ceased after replacement of a catalyst. Very recently, however, patients have started to report symptoms that suggest a new allergic reaction from polyether impression materials. Here, we report on the results of allergy testing with polyether impression materials as well as with its components. Eight patients with clinical symptoms of a contact allergy (swelling, redness or blisters) after exposure to a polyether impression material were subjected to patch tests, two of them additionally to a prick test. A further patient with atypical symptoms of an allergy (nausea and vomiting after contact with a polyether impression material in the oral cavity) but with a history of other allergic reaction was also patch tested. The prick tests showed no immediate reactions in the two patients tested. In the patch tests, all eight patients with typical clinical symptoms showed positive reactions to the mixed polyether impression materials, to the base paste or to a base paste component. The patient with the atypical clinical symptoms did not show any positive patch test reactions. Polyether impression materials may evoke type IV allergic reactions. The causative agent was a component of the base paste. In consideration of the widespread use of this impression material (millions of applications per year) and in comparison to the number of adverse reactions from other dental materials, the number of such allergic reactions is very low. In very scarce cases, positive allergic reactions to polyether impression materials are possible.
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Identification of new genes associated with melanoma.
Exp. Dermatol.
PUBLISHED: 03-16-2011
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Repeated failures in melanoma therapy made clear that the molecular mechanisms leading to melanoma are still poorly understood. In this study, we aim to provide a more comprehensive understanding of the transcriptional profiles and signalling pathways associated with melanoma.
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A new star on the H?O?rizon of wound healing?
Exp. Dermatol.
PUBLISHED: 02-18-2011
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A breakthrough finding has shown that hydrogen peroxide (H(2)O(2)) gradients contribute to recruit leucocytes to the wound site during the inflammatory phase of healing. It was in 1992 that NO was awarded molecule of the year because of the discovery that such a tiny chemical may act as an important signalling molecule, thereby influencing research over decades. We speculate that H(2)O(2) also has the potential to have a broad impact on research over years, especially in mammalian wound healing. To justify our hypothesis, we provide evidence from the literature on (i) how H(2)O(2) gradients are created, (ii) how H(2)O(2) acts in the physiological phases of wound healing and (iii) a possible role of H(2)O(2) in bacterial defense - bacterial colonization being one of the major problems in chronic wounds. Based on this, we provide the first overview on how H(2)O(2) acts during the different wound healing phases.
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Laser and IPL treatment of port-wine stains: therapy options, limitations, and practical aspects.
Lasers Med Sci
PUBLISHED: 01-26-2011
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Port-wine stains (PWS) are congenital, progressive vascular malformations of the dermis that are often disfiguring, particularly when located in a cosmetically relevant area. Thus, the successful clearance of PWS is of highest medical relevance, and laser therapy is the treatment of choice for this indication. Numerous trials have shown the effectiveness of both lasers and incoherent light sources. Laser or IPL treatments achieve good clearance in the majority of PWS, but complete clearance is rare. Thus, new therapeutic options are urgently required. Photodynamic therapy is a relatively new approach in the treatment of PWS. Our review aims to summarize therapy options of port-wine stains, depending on treatment area, patient age, and vessel architecture. Recent developments in this field and new insights into the pathogenesis of PWS are discussed. The review also highlights practical aspects, complications that can occur, and how to prevent them.
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Distinct profile of the mitochondrial DNA common deletion in benign skin lesions.
Exp. Dermatol.
PUBLISHED: 01-25-2011
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Mutations of mitochondrial (mt) DNA, particularly the 4977 bp long common deletion, are increased in aging tissues and preferentially found in chronologically and photoaged skin. Mutations of human mitochondrial DNA (mtDNA) have also been identified in malignant tumors of the skin and of other organs. However, benign skin lesions have not yet been investigated. We analyzed the frequency of the common deletion in 27 benign skin lesions [8 seborrheic keratoses (SK), 5 epidermal nevi (EN), 14 solar lentigos (SL)] by quantitative real-time PCR, because SK and especially SL have been related to (photo)aged skin. All SK and four of five EN displayed reduced common deletion levels compared with adjacent normal skin. In contrast, 50% of SL revealed a higher percentage of the common deletion than the adjacent normal skin, and some SL showed very high absolute common deletion levels up to 14% of total mtDNA. Our results show that the amount of the common deletion is significantly different in benign skin lesions and raise further questions regarding the pathogenesis of SL and its possible role as a precursor lesion of SK.
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2D luminescence imaging of pH in vivo.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 01-24-2011
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Luminescence imaging of biological parameters is an emerging field in biomedical sciences. Tools to study 2D pH distribution are needed to gain new insights into complex disease processes, such as wound healing and tumor metabolism. In recent years, luminescence-based methods for pH measurement have been developed. However, for in vivo applications, especially for studies on humans, biocompatibility and reliability under varying conditions have to be ensured. Here, we present a referenced luminescent sensor for 2D high-resolution imaging of pH in vivo. The ratiometric sensing scheme is based on time-domain luminescence imaging of FITC and ruthenium(II)tris-(4,7-diphenyl-1,10-phenanthroline). To create a biocompatible 2D sensor, these dyes were bound to or incorporated into microparticles (aminocellulose and polyacrylonitrile), and particles were immobilized in polyurethane hydrogel on transparent foils. We show sensor precision and validity by conducting in vitro and in vivo experiments, and we show the versatility in imaging pH during physiological and chronic cutaneous wound healing in humans. Implementation of this technique may open vistas in wound healing, tumor biology, and other biomedical fields.
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Experience with non-ablative fractional photothermolysis with a dual-mode laser device (1,440/1,320 nm): no considerable clinical effect on hypertrophic/acne scars and facial wrinkles.
Lasers Med Sci
PUBLISHED: 01-18-2011
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In the literature, non-ablative fractionated photothermolysis (nFP) is accredited with improvement of wrinkles and scars combined with a reduced downtime. The purpose of this work was to evaluate the impact of a combination laser (1,320/1,440 nm) for nFP on hypertrophic scars, acne scars, and facial wrinkles. Thirty-six patients suffering from hypertrophic scars (n?=?7), acne scars (n?=?9), and wrinkles (n?=?20) were treated using a combination Nd:YAG laser [?(em)?=?1,320 and 1,440 nm, pulse duration: 3-ms single pulse, fluence: 8.0-9.0 J/cm(2) (1,320 nm); 2.0-2.5 J/cm(2) (1,440 nm)]. The appearance of the treated condition was evaluated in a retrospective study by two blinded investigators based on follow-up photographs and by patient self-assessment. The frequency of side-effects was also assessed. Both patients and blinded observers rated the treatment results for hypertrophic scars and acne scars as slight improvement, and for wrinkles as equal as compared to baseline. No serious side-effects were reported. The light device used did not lead to a considerable clinical improvement of hypertrophic scars, acne scars, or wrinkles in this study.
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Photodynamic inactivation of multi-resistant bacteria (PIB) - a new approach to treat superficial infections in the 21st century.
J Dtsch Dermatol Ges
PUBLISHED: 11-26-2010
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The increasing resistance of bacteria against antibiotics is one of the most important clinical challenges of the 21(st) century. Within the gram-positive bacteria the methicillin-resistant Staphylococcus aureus and Enterococcus faecium represent the major obstacle to successful therapy. Apart from the development of new antibiotics it requires additional differently constituted approaches, like photodynamic inactivation in order to have further effective treatment options against bacteria available. Certain dyes, termed photosensitizers, are able to store the absorbed energy in long-lived electronic states upon light activation with appropriate wavelengths and thus make these states available for chemical activation of the immediate surroundings. The interaction with molecular oxygen, which leads to different, very reactive and thus cytotoxic oxygen species, is highlighted. In this review the application of the photodynamic inactivation of bacteria will be discussed regarding the possible indications in dermatology, like localized skin and wound infections or the reduction of nosocomial colonization with multi-resistant bacteria on the skin. The crucial advantage of the local application of photosensitizers followed by irradiation of the area of interest is the fact that independent of the resistance pattern of a bacterium a direct inactivation takes place similarly as with an antiseptic. In this review the physical-chemical and biological basics of photo-dynamic inactivation of bacteria (PIB) will be discussed as well as the possible dermatological indications.
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Multiple oncogenic mutations and clonal relationship in spatially distinct benign human epidermal tumors.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-15-2010
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Malignant tumors result from the accumulation of genetic alterations in oncogenes and tumor suppressor genes. Much less is known about the genetic changes in benign tumors. Seborrheic keratoses (SK) are very frequent benign human epidermal tumors without malignant potential. We performed a comprehensive mutational screen of genes in the FGFR3-RAS-MAPK and phosphoinositide 3-kinase (PI3K)-AKT pathways from 175 SK, including multiple lesions from each patient. SK commonly harbored multiple bona fide oncogenic mutations in FGFR3, PIK3CA, KRAS, HRAS, EGFR, and AKT1 oncogenes but not in tumor suppressor genes TSC1 and PTEN. Despite the occurrence of oncogenic mutations and the evidence for downstream ERK/MAPK and PI3K pathway signaling, we did not find induction of senescence or a DNA damage response. Array comparative genomic hybridization (aCGH) analysis revealed that SK are genetically stable. The pattern of oncogenic mutations and X chromosome inactivation departs significantly from randomness and indicates that spatially independent lesions from a given patient share a clonal relationship. Our findings show that multiple oncogenic mutations in the major signaling pathways involved in cancer are not sufficient to drive malignant tumor progression. Furthermore, our data provide clues on the origin and spread of oncogenic mutations in tissues, suggesting that apparently independent (multicentric) adult benign tumors may have a clonal origin.
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Antiproliferative effects of rapamycin and celecoxib in angiosarcoma cell lines.
Anticancer Res.
PUBLISHED: 11-02-2010
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Beyond their primary field of application some well-established drugs exhibit antitumour effects in a variety of cancers. The aim of this study was to investigate the effects of the COX2 inhibitor celecoxib and the mTOR antagonist rapamycin on angiosarcoma cell lines.
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Quality of life in health care of non-melanoma skin cancer - results of a pilot study.
J Dtsch Dermatol Ges
PUBLISHED: 10-28-2010
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Modern patient-oriented medicine increasingly involves psychosocial aspects of disease processes in therapy evaluations. We conducted a pilot study on the implementation of a suitable device assessing the quality of life of patients with non-melanoma skin cancer (NMSC) in clinical routine.
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Skin rejuvenation with intense pulsed light.
Acta Dermatovenerol Croat
PUBLISHED: 10-05-2010
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Skin rejuvenation has developed into one of the most popular indications for laser and intense pulsed light (IPL) treatment in dermatology. During the past few years, nonablative skin rejuvenation with infrared lasers has become ever more popular. The results for hyperpigmentation, telangiectasias and erythema are very good, whereas the results in treating wrinkles are not as good as with ablative therapy.
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Split-face comparison of intense pulsed light with short- and long-pulsed dye lasers for the treatment of port-wine stains.
Lasers Surg Med
PUBLISHED: 10-02-2010
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So far, pulsed dye lasers have been regarded as the gold standard in the treatment of port-wine stains (PWS). Recently, intense pulsed light (IPL) has been reported to achieve more pronounced fading in some patients.
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Management of split-thickness donor sites with synthetic wound dressings: results of a comparative clinical study.
Ann Plast Surg
PUBLISHED: 09-16-2010
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This prospective, randomized, single-blinded, clinical study aimed at evaluating 3 different synthetic wound dressings for treating split-thickness skin graft donor sites. Seventy-seven patients were randomly assigned to 3 study groups: Suprathel, Biatain-Ibu, Mepitel. Wounds were inspected daily until complete reepithelization. Ease of care, treatment costs, and scar development after a 6 months follow-up were evaluated. Suprathel showed significant (P ? 0.001) pain reduction after 24 hours but increasing pain scores on the 5th day of treatment. Biatain-Ibu showed significant pain relief immediately after application and during the entire treatment period (P < 0.05). Mepitel did not show any significant pain reduction. No differences were seen with regard to healing time, quality of reepithelization, and scar development. Biatain-Ibu had the lowest overall treatment costs (P ? 0.001). The investigated materials did not differ with regard to quality and acceleration of the healing process, but Biatain-Ibu seems to be the most appropriate dressing material in terms of cost-effectiveness.
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Permanent make-up colorants may cause severe skin reactions.
Contact Derm.
PUBLISHED: 09-14-2010
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In recent years, cosmetic tattoos [permanent make-up (PMU)] on eyelids, eyebrows and lips have become increasingly popular. However, most colorants are manufactured for non-medical purposes, without any established history of safe use in humans.
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Amyloid in skin and brain: whats the link?
Exp. Dermatol.
PUBLISHED: 08-27-2010
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For too long, amyloids have been under general suspicion to merely cause diseases. In recent years, we have learned that these interesting proteins may also fulfill important biological tasks. Moreover, recent publications show emerging evidence for a so-called brain-skin axis. This viewpoint paper aims to address the question what is known about the link between brain and skin based on the literature available for two diseases caused by amyloid formation: Alzheimers disease (AD) and cutaneous amyloidoses. In addition, we acquaint the reader with a different perspective on the role of amyloid in skin and brain.
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Cyclosporin combined with methotrexate in two patients with recalcitrant subacute cutaneous lupus erythematosus.
Australas. J. Dermatol.
PUBLISHED: 08-24-2010
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The treatment of subacute cutaneous lupus erythematosus is a therapeutic challenge. Frequently, patients are resistant to or intolerant towards single selected immunosuppressants. In combination, lower doses of methotrexate and cyclosporin A might be used to minimize toxicity. This is the first report of a successful combination of these drugs in two patients suffering from subacute cutaneous lupus erythematosus refractory to standard treatment.
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Plasma medicine: possible applications in dermatology.
J Dtsch Dermatol Ges
PUBLISHED: 08-13-2010
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As a result of both the better understanding of complex plasma phenomena and the development of new plasma sources in the past few years, plasma medicine has developed into an innovative field of research showing high potential. While thermal plasmas have long been used in various medical fields (for instance for cauterization and sterilization of medical instruments), current research mainly focuses on application of non-thermal plasmas. Experiments show that cold atmospheric plasmas (CAPs) allow efficient, contact-free and painless disinfection, even in microscopic openings, without damaging healthy tissue. Plasmas influence biochemical processes and offer new possibilities for the selective application of individually designable medically active substances. In dermatology, new horizons are being opened for wound healing, tissue regeneration, therapy of skin infections, and probably many more diseases. First clinical trials show the efficacy and tolerability of plasma in treating infected chronic wounds. A major task will be the introduction of plasma into clinical medicine and, simultaneously, the further investigation of the mechanisms of action of plasma at the cellular level.
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Photodynamic therapy in dermatology: state-of-the-art.
Photodermatol Photoimmunol Photomed
PUBLISHED: 06-30-2010
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Photodynamic therapy (PDT) has become an established treatment modality for dermatooncologic conditions like actinic keratosis, Bowens disease, in situ squamous cell carcinoma and superficial basal cell carcinoma. There is also great promise of PDT for many non-neoplastic dermatological diseases like localized scleroderma, acne vulgaris, granuloma anulare and leishmaniasis. Aesthetic indications like photo-aged skin or sebaceous gland hyperplasia complete the range of applications. Major advantages of PDT are the low level of invasiveness and the excellent cosmetic results. Here, we review the principal mechanism of action, the current developments in the field of photosensitizers and light sources, practical aspects of topical PDT and therapeutical applications in oncologic as well as non-oncologic indications.
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Wound healing in the 21st century.
J. Am. Acad. Dermatol.
PUBLISHED: 06-23-2010
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Delayed wound healing is one of the major therapeutic and economic issues in medicine today. Cutaneous wound healing is an extremely well-regulated and complex process basically divided into 3 phases: inflammation, proliferation, and tissue remodeling. Unfortunately, we still do not understand this process precisely enough to give direction effectively to impaired healing processes. There have been many new developments in wound healing that provide fascinating insights and may improve our ability to manage clinical problems. Our goal is to acquaint the reader with selected major novel findings about cutaneous wound healing that have been published since the beginning of the new millennium. We discuss advances in areas such as genetics, proteases, cytokines, chemokines, and regulatory peptides, as well as therapeutic strategies, all set in the framework of the different phases of wound healing.
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Activation of the PI3K/AKT signalling pathway in non-melanoma skin cancer is not mediated by oncogenic PIK3CA and AKT1 hotspot mutations.
Exp. Dermatol.
PUBLISHED: 06-19-2010
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Non-melanoma skin cancer represents the most frequent human cancer entity. Activation of the PI3K/AKT signalling pathway has been reported both in squamous cell carcinoma (SCC) of the skin and in basal cell carcinoma (BCC). In many cancers, including SCC of the head and neck, the oesophagus and the penis, activation of this pathway is mediated by oncogenic PIK3CA and AKT1 mutations. We therefore screened 61 non-melanoma skin cancer samples (30 SCC and 31 BCC) for the presence of activating PIK3CA and AKT1 mutations. PIK3CA hotspot mutations were analysed using a highly sensitive SNaPshot assay, and exon 4 of AKT1 was sequenced directly. In addition, immunohistochemistry was performed for phosphorylated AKT protein. Immunohistochemical expression of pAkt was observed both in SCC and in BCC samples, indicating an activation of the PI3K/AKT pathway. Although SCC showed higher expression levels than BCC, this difference was not significant. However, none of the 61 non-melanoma skin cancer samples revealed any PIK3CA and AKT1 hotspot mutations at the investigated loci. We conclude that PIK3CA and AKT1 hotspot mutations do not contribute to the activation of the PI3K/AKT signalling pathway in non-melanoma skin cancer. The distinct PIK3CA mutation spectrum between SCC of the skin and SCC of other tissues may reflect the different carcinogens which are involved into the mutagenesis of these cancers. PIK3CA and AKT1 hotspot mutations are obviously not caused by UV light exposure, the main risk factor in non-melanoma skin cancer.
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Tattoo inks contain polycyclic aromatic hydrocarbons that additionally generate deleterious singlet oxygen.
Exp. Dermatol.
PUBLISHED: 06-16-2010
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In the past years, tattoos have become very popular worldwide, and millions of people have tattoos with mainly black colours. Black tattoo inks are usually based on soot, are not regulated and may contain hazardous polycyclic aromatic hydrocarbons (PAHs). Part of PAHs possibly stay lifelong in skin, absorb UV radiation and generate singlet oxygen, which may affect skin integrity. Therefore, we analysed 19 commercially available tattoo inks using HPLC and mass spectrometry. The total concentrations of PAHs in the different inks ranged from 0.14 to 201 microg/g tattoo ink. Benz(a)pyrene was found in four ink samples at a mean concentration of 0.3 +/- 0.2 microg/g. We also found high concentrations of phenol ranging from 0.2 to 385 microg/g tattoo ink. PAHs partly show high quantum yields of singlet oxygen (Phi(Delta)) in the range from 0.18 to 0.85. We incubated keratinocytes with extracts of different inks. Subsequent UVA irradiation decreased the mitochondrial activity of cells when the extracts contained PAHs, which sufficiently absorb UVA and show simultaneously high Phi(Delta) value. Tattooing with black inks entails an injection of substantial amounts of phenol and PAHs into skin. Most of these PAHs are carcinogenic and may additionally generate deleterious singlet oxygen inside the dermis when skin is exposed to UVA (e.g. solar radiation).
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Dysplastic melanocytic nevi of the lower leg: sex- and site-specific histopathology.
Am J Dermatopathol
PUBLISHED: 06-11-2010
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Site-specific histopathology features have been reported for acral, auricular, flexural, and genital melanocytic nevi, however, to the best of our knowledge, site- and sex-specific histology of dysplastic nevi on the lower leg (between knee and ankle) of women (DN-LW) has not been reported. In this retrospective histopathology study, we compared DN-LW (N = 42) with appropriate control groups of (1) DN of the lower leg of men (N = 20; DN-LM), (2) DN from the back of women (N = 20), (3) common nevi of the lower leg of women (N = 40), and (4) levels 1-2 superficial spreading melanoma of the lower leg of women (N = 20). Compared with dysplastic nevi on the back, DN-LW were smaller in diameter and exhibited a significantly higher score for pagetoid spread (P < 0.05). DN-LW compared with DN-LM showed sex-specific differences with (1) pagetoid spread (P < 0.05), (2) cytologic atypia (P < 0.05), (3) presence of large melanocytes (P < 0.05), and (4) band-like pigmentation in the dermis underlying the nevus (54% in DN-LW vs. 15% in DN-LM). As with other body sites, the dermatopathologist should be aware that dysplastic nevi occurring on the lower leg in women have site- and sex-specific features. Knowing this profile may lower the risk of misdiagnosing DN-LW and melanoma of the lower leg of women.
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Methylthioadenosine phosphorylase represents a predictive marker for response to adjuvant interferon therapy in patients with malignant melanoma.
Exp. Dermatol.
PUBLISHED: 05-27-2010
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Using tissue microarrays assembling 465 nevi, primary melanomas and metastases, we investigated whether expression of methylthioadenosine phosphorylase (MTAP), a recently suggested biomarker of malignant melanoma, has prognostic significance and may predict responsiveness to adjuvant interferon therapy in patients with melanoma. Because of its association with MTAP activity and interferon signalling pathways, signal transducer and activator of transcription 1 (STAT1) immunohistochemistry was analysed, too. MTAP expression was significantly reduced in melanomas and metastases compared with nevi (P < 0.001); STAT1 expression significantly increased. In melanomas, loss of MTAP expression was significantly related to Clark level (P < 0.05) and tumor thickness (P < 0.01); whereas STAT1 immunoreactivity was significantly related to gender (p < 0.05) and tumor thickness (P < 0.05). Interestingly, subgroup analysis of patients with a tumor thickness of 1.5-4.0 mm revealed a significant survival benefit from adjuvant interferon treatment regarding recurrence-free survival (RFS; P < 0.05) if MTAP expression was observed in the primary melanoma. Patients with STAT1-positive melanomas also tended to benefit from interferon concerning RFS (P = 0.074) and showed a significant benefit concerning overall survival (OS; P < 0.05). According to Cox analysis, MTAP expression in contrast to STAT1 was an independent positive prognostic marker for RFS and OS. In conclusion, MTAP represents a highly promising immunohistochemical marker for prognosis and interferon response of patients with malignant melanoma.
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Incidence of health problems associated with tattooed skin: a nation-wide survey in German-speaking countries.
Dermatology (Basel)
PUBLISHED: 03-09-2010
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Millions of people are tattooed. However, the frequency of health problems is unknown.
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Generalized solar lentigines in a patient with a history of radon exposure.
Dermatology (Basel)
PUBLISHED: 03-02-2010
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A woman with generalized lentigines without associated non-cutaneous abnormalities is described. The patient showed brownish-pigmented flat or slightly elevated spots with a diameter of 1–5 mm. The histopathology of the lesions was compatible with a diagnosis of solar lentigines (SLs) or flat seborrhoeic keratosis. Unlike SLs, which develop typically on sun-damaged skin of the face, the dorsum of the hands and forearms, this patient showed the lentigines most prominently on the thighs and lower legs. Besides increased recreational UV exposure, the patient had a history of occupational radon exposure in a spa with radon-containing water. Genetic analysis identified a p.S249C FGFR3 hotspot mutation in 1 lesion, supporting the diagnosis of SLs. It remains elusive whether the occupational exposure to radon-containing water in addition to the recreational UV light exposure caused the unusual distribution of the SLs in this patient.
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Pityriasis rubra pilaris: a review of diagnosis and treatment.
Am J Clin Dermatol
PUBLISHED: 02-27-2010
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Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis of unknown etiology, and finding a successful therapy can be challenging. PRP occurs equally in men and women. In some patients, associated autoimmune diseases, infections, or malignancies are possible trigger factors. PRP shows a bimodal age distribution, peaking in the first as well as in the fifth to sixth decade. Its classification into five subgroups is based on age at onset, clinical course, morphologic features, and prognosis. More than 50% of patients are best classified as type I with adult-onset PRP. This form is also characterized by high spontaneous remission rates (80%) within 1-3 years. Clinically, the classical adult (type I) and classical juvenile (type III) forms appear to be the same except for the patients age. Recently, the designation of a new category of PRP (type VI) has been proposed that is characterized by the presence of HIV infection with different clinical features and a poorer prognosis. Typical morphologic features of PRP are erythematosquamous salmon-colored plaques with well demarcated islands of unaffected skin. Often, keratoderma of the palms and soles is present. In patients with extensive disease, ectropion is a dreaded complication. Histology shows hyperkeratosis, alternating orthokeratosis and parakeratosis in a checkerboard pattern, and focal acantholytic dyskeratosis. Descriptions and therapeutic experiences are mainly based on case reports. Mostly, systemic retinoids, methotrexate, and other immunosuppressive agents as well as UV light therapy are applied, with varying response rates. In recent years, treatment with so-called biologics is becoming more and more popular for treating recalcitrant PRP. We present a review of the clinical features, histopathologic findings, classification, differential diagnoses, and treatment of PRP.
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FGFR3 mutation affects cell growth, apoptosis and attachment in keratinocytes.
Exp. Cell Res.
PUBLISHED: 02-22-2010
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FGFR3 mutations have recently been identified in several benign epidermal skin lesions such as seborrheic keratosis, epidermal nevus and solar lentigo. The functional consequences of these mutations in human skin are as yet unknown. In this study we analyzed the functional effects of the most common FGFR3 mutation in benign skin tumors, the R248C FGFR3 hotspot mutation, in human HaCaT keratinocytes. The cells were stably transduced with either the R248C or wildtype FGFR3 IIIb cDNA using a retroviral vector system. FGFR3 mutant and wildtype cells showed similar growth rates at subconfluence. However, at confluence FGFR3 mutant keratinocytes revealed a significantly higher cell number than wildtype cells. Furthermore, FGFR3 mutant cells showed significantly lower levels of apoptosis and decreased attachment to fibronectin compared with FGFR3 wildtype cells. Expression of mutant FGFR3 did not alter migration and senescence. Microarray analysis revealed only a few differentially expressed genes between FGFR3 mutant and wildtype keratinocytes. Enhanced phosphorylation of ERK1/2 was observed in confluent R248C mutant HaCaT cells compared with wildtype keratinocytes. Our results suggest that an increased cell number at confluence along with a decreased apoptosis may contribute to the development of acanthotic tumors in FGFR3 mutant skin in vivo.
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Intense pulsed light (IPL): a review.
Lasers Surg Med
PUBLISHED: 02-19-2010
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Intense pulsed light (IPL) devices use flashlamps and bandpass filters to emit polychromatic incoherent high-intensity pulsed light of determined wavelength spectrum, fluence, and pulse duration. Similar to lasers, the basic principle of IPL devices is a more or less selective thermal damage of the target. The combination of prescribed wavelengths, fluences, pulse durations, and pulse intervals facilitates the treatment of a wide spectrum of skin conditions.
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Photodynamic therapy in dermatology.
J Dtsch Dermatol Ges
PUBLISHED: 02-03-2010
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Photodynamic therapy (PDT) is a modern therapy modality, based upon the application of a photosensitizing agent like aminolevulinic acid, a physiological precursor of porphyrins, onto the tissue followed by illumination with light of the visible wavelength spectrum. During this oxygen-dependent reaction, reactive oxygen species (ROS) are generated that have immunomodulatory or cytotoxic effects. PDT shows excellent cosmetic results especially for its key indication in dermatology - the treatment of non-melanoma skin cancer. The associated pain and the low tissue penetration are the most frequent limiting factors of PDT. We review basic principles and recent developments in photosensitizers and light sources. Key oncological and non-oncological indications are presented as well.
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Cutaneous amyloidoses and systemic amyloidoses with cutaneous involvement.
Eur J Dermatol
PUBLISHED: 01-14-2010
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Extracellular deposition of altered autologous protein (amyloid protein) within the dermis is the hallmark of cutaneous amyloidoses and systemic amyloidoses with cutaneous involvement. Amyloidoses may be acquired or hereditary in nature and subclassification differentiates between primary amyloidosis (no obvious predisposing disease) and secondary amyloidosis (specific underlying disease). More than 26 different proteins and peptides have been identified as amyloid precursors and these proteins are used to subclassify this heterogeneous group of diseases. The amyloid proteins show an anti-parallel beta-sheet conformation and form non-branching linear filaments of variable lengths and diameters of approximately 7.5 to 10 nm. However, the exact etiopathogenesis of amyloid formation still remains unclear. Depending on histoanatomical distribution and amount, amyloid may cause progressive and life-threatening organ dysfunction. Clinical presentation, histology, electron microscopy, and biochemical-immunological differentiation represent decisive tools for an accurate diagnosis.
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Phototoxic reactions in healthy volunteers following photodynamic therapy with methylaminolevulinate cream or with cream containing 5-aminolevulinic acid: a phase II, randomized study.
Photodermatol Photoimmunol Photomed
PUBLISHED: 09-15-2009
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Photodynamic therapy (PDT) is the selective destruction of abnormal cells through activation of a photosensitizer in the presence of oxygen. Local phototoxic reactions and pain are the most common limiting side effects.
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Tattooing of skin results in transportation and light-induced decomposition of tattoo pigments--a first quantification in vivo using a mouse model.
Exp. Dermatol.
PUBLISHED: 08-23-2009
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Millions of people are tattooed with inks that contain azo pigments. The pigments contained in tattoo inks are manufactured for other uses with no established history of safe use in humans and are injected into the skin at high densities (2.5 mg/cm(2)). Tattoo pigments disseminate after tattooing throughout the human body and although some may photodecompose at the injection site by solar or laser light exposure, the extent of transport or photodecomposition under in vivo conditions remains currently unknown. We investigated the transport and photodecomposition of the widely used tattoo Pigment Red 22 (PR 22) following tattooing into SKH-1 mice. The pigment was extracted quantitatively at different times after tattooing. One day after tattooing, the pigment concentration was 186 microg/cm(2) skin. After 42 days, the amount of PR 22 in the skin has decreased by about 32% of the initial value. Exposure of the tattooed skin, 42 days after tattooing, to laser light reduced the amount of PR 22 by about 51% as compared to skin not exposed to laser light. A part of this reduction is as a result of photodecomposition of PR 22 as shown by the detection of corresponding hazardous aromatic amines. Irradiation with solar radiation simulator for 32 days caused a pigment reduction of about 60% and we again assume pigment decomposition in the skin. This study is the first quantitative estimate of the amount of tattoo pigments transported from the skin into the body or decomposed by solar or laser radiation.
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Topical photodynamic therapy with porphyrin precursors--assessment of treatment-associated pain in a retrospective study.
Photochem. Photobiol. Sci.
PUBLISHED: 06-10-2009
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Photodynamic therapy (PDT) with aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) is an approved modality for the non-invasive treatment of actinic keratoses (AK) and basal cell carcinoma (BCC) offering excellent cosmetic outcome. However, pain during and after illumination is the most frequent and limiting side effect. The aim of this study was to precisely assess how reported pain during PDT is influenced by sex, age, treatment site, disease (AK/BCC) as well as the photosensitizer used. 467 lesions consisting of AK (primary treatments: n=158; follow-up: n=47) or BCC (primary treatments: n=138; follow-up: 124) were treated by ALA- or MAL-PDT using metal halide lamps (580-750 nm). Pain was assessed during illumination using a continuous visual analogue scale (VAS). Factors predictive for higher pain levels during PDT are treatment of the head, treating AK and using ALA. The observed results may improve patient management and predict which level of pain to expect, and what kind of pain relief to prepare.
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Crohns disease: an important differential diagnosis of granulomatous skin diseases.
Eur J Dermatol
PUBLISHED: 05-14-2009
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Metastatic Crohns disease is a very rare skin manifestation of Crohns disease. Its time of occurrence and severity do not necessarily correlate with the intestinal disease. The main characteristic is that the granulomatous skin changes occur at sites distant from the bowel. We report the case of a 65-year-old woman with metastatic Crohns disease on her right lower leg without clinical intestinal signs at the time of diagnosis. The inflammatory pustulating skin lesions resolved after systemic and topical treatment with corticosteroids. After reducing immunosuppressive therapy, fistulating lesions reappeared on the lower legs and at the mons pubis. Coloscopy now, more than five years after the onset of the first skin lesions, showed an intestinal Crohns disease. Metastatic Crohns disease and its differential diagnoses with granulomatous reaction pattern are discussed in this manuscript.
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Melanoma promotion after photodynamic therapy of a suspected Bowens disease lesion.
Dermatology (Basel)
PUBLISHED: 04-11-2009
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We report on a 61-year-old male patient who developed a melanoma at the site of a suspected Bowens lesion on the right cheek. This lesion had evolved for years and had been treated using photodynamic therapy (PDT) in an outpatient facility. Only a couple of months after a single PDT treatment, a melanoma was histologically diagnosed. After excision, multiple metastases were found. The therapeutic strategy comprised re-excision, neck dissection and lateral parotidectomy - due to a metastasis - as well as subsequent alpha-interferon injections. The possible role of PDT in the promotion of melanoma is discussed.
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Adjuvant photodynamic therapy does not prevent recurrence of condylomata acuminata after carbon dioxide laser ablation-A phase III, prospective, randomized, bicentric, double-blind study.
Dermatol Surg
PUBLISHED: 03-23-2009
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Recurrence after therapy for anogenital warts, or condylomata acuminata (CA), is common. Topical photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) is efficient in the treatment of CA, but one problem with PDT is the limited penetration depth of photosensitizer and light. Pre-PDT vaporization of CA using a carbon dioxide (CO(2)) laser may enhance efficacy.
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Cyclooxygenase 2 (COX2) and Peroxisome Proliferator-Activated Receptor Gamma (PPARG) Are Stage-Dependent Prognostic Markers of Malignant Melanoma.
PPAR Res
PUBLISHED: 03-10-2009
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Using tissue microarrays (TMAs) we studied COX2/PPARG immunoreactivity in a broad spectrum of tumors focussing on clinicopathological correlations and the outcome of patients with malignant melanoma (MM). TMA-1 contained normal and tumor tissues (n = 3448) from 47 organs including skin neoplasms (n = 323); TMA-2 88 primary MM, 101 metastases, and 161 benign nevi. Based on a biomodulatory approach combining COX/PPAR-targeting with metronomic low-dose chemotherapy metastases of 36 patients participating in a randomized trial with metastatic (stage IV) melanoma were investigated using TMA-3. COX2/PPARG immunoreactivity significantly increased from nevi to primary MM and metastases; COX2 positivity was associated with advanced Clark levels and shorter recurrence-free survival. Patients with PPARG-positive metastases and biomodulatory metronomic chemotherapy alone or combined with COX2/PPARG-targeting showed a significantly prolonged progression-free survival. Regarding primary MM, COX2 expression indicates an increased risk of tumor recurrence. In metastatic MM, PPARG expression may be a predicitive marker for response to biomodulatory stroma-targeted therapy.
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Confocal laser scanning microscopy--evaluation of native tissue sections in micrographic surgery.
Lasers Med Sci
PUBLISHED: 01-15-2009
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Micrographic surgery is mainly used for excising basal cell carcinomas in high-risk body sites. The time-consuming process of frozen histopathology could be potentially accelerated by the application of ex vivo confocal laser scanning microscopy (CM). We examined the margins of 52 excised basal cell carcinomas by means of CM, and compared the results to conventional histological findings. For contrast enhancement, tissues were treated with 10% citric acid. The morphologic features of tumors seen in CM corresponded well to conventional light microscopy. Confocal assessment and light microscopical findings were consistent in 84.6%. If a tumor is clearly detectable by means of CM, the procedure of micrographic surgery can be accelerated. Negative confocal findings have yet to be confirmed by conventional microscopy. Applicability of CM is limited because of an inconsistent image quality that does not allow a reliable detection of small tumor nests. Further research into the handling of the samples and into specific contrast enhancement is necessary for CM to become a widely accepted procedure in micrographic surgery.
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Clonality of basal cell carcinoma arising in an epidermal nevus. New insights provided by molecular analysis.
Dermatology (Basel)
PUBLISHED: 01-06-2009
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Non-organoid non-epidermolytic (keratinocytic) epidermal nevi are benign congenital skin lesions following the lines of Blaschko. The occurrence of epithelial tumors in epidermal nevi of this type is very rare, and it remains elusive whether these lesions are clonally related or represent a simple collision of independent tumors. We report a case of a patient who developed 2 basal cell carcinomas in an extensive epidermal nevus on the trunk. Molecular analysis of a biopsy containing both basal cell carcinoma and epidermal nevus revealed a PIK3CA mutation. Further analysis suggested that this mutation is present in the basal cell carcinoma rather than in the epidermal nevus. The results favour an independent origin of the basal cell carcinoma, although a possible clonal relationship between both lesions cannot be completely excluded on the basis of the molecular genetic findings.
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A sprayable luminescent pH sensor and its use for wound imaging in vivo.
Exp. Dermatol.
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Non-invasive luminescence imaging is of great interest for studying biological parameters in wound healing, tumors and other biomedical fields. Recently, we developed the first method for 2D luminescence imaging of pH in vivo on humans, and a novel method for one-stop-shop visualization of oxygen and pH using the RGB read-out of digital cameras. Both methods make use of semitransparent sensor foils. Here, we describe a sprayable ratiometric luminescent pH sensor, which combines properties of both these methods. Additionally, a major advantage is that the sensor spray is applicable to very uneven tissue surfaces due to its consistency. A digital RGB image of the spray on tissue is taken. The signal of the pH indicator (fluorescein isothiocyanate) is stored in the green channel (G), while that of the reference dye [ruthenium(II)-tris-(4,7-diphenyl-1,10-phenanthroline)] is stored in the red channel (R). Images are processed by rationing luminescence intensities (G/R) to result in pseudocolor pH maps of tissues, e.g. wounds.
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Adjuvant therapy with pegylated interferon alfa-2b (36 months) versus low-dose interferon alfa-2b (18 months) in melanoma patients without macrometastatic nodes: an open-label, randomised, phase 3 European Association for Dermato-Oncology (EADO) study.
Eur. J. Cancer
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Both low-dose interferon (IFN) alfa-2b and pegylated interferon (Peg-IFN) alfa-2b have been shown to be superior to observation in the adjuvant treatment of melanoma without macrometastatic nodes, but have never been directly compared. Peg-IFN facilitates prolongation of treatment, which could provide additional benefit. This multicentre, open-label, randomised, phase 3 trial compared standard low-dose interferon IFN and prolonged treatment with Peg-IFN.
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A seven-marker signature and clinical outcome in malignant melanoma: a large-scale tissue-microarray study with two independent patient cohorts.
PLoS ONE
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Current staging methods such as tumor thickness, ulceration and invasion of the sentinel node are known to be prognostic parameters in patients with malignant melanoma (MM). However, predictive molecular marker profiles for risk stratification and therapy optimization are not yet available for routine clinical assessment.
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Postzygotic HRAS and KRAS mutations cause nevus sebaceous and Schimmelpenning syndrome.
Nat. Genet.
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Nevus sebaceous is a common congenital cutaneous malformation. Affected individuals may develop benign and malignant secondary tumors in the nevi during life. Schimmelpenning syndrome is characterized by the association of nevus sebaceous with extracutaneous abnormalities. We report that of 65 sebaceous nevi studied, 62 (95%) had mutations in the HRAS gene and 3 (5%) had mutations in the KRAS gene. The HRAS c.37G>C mutation, which results in a p.Gly13Arg substitution, was present in 91% of lesions. Nonlesional tissues from 18 individuals had a wild-type sequence, confirming genetic mosaicism. The HRAS c.37G>C mutation was also found in 8 of 8 associated secondary tumors. Mosaicism for HRAS c.37G>C and KRAS c.35G>A mutations was found in two individuals with Schimmelpenning syndrome. Functional analysis of HRAS c.37G>C mutant cells showed constitutive activation of the MAPK and PI3K-Akt signaling pathways. Our results indicate that nevus sebaceous and Schimmelpenning syndrome are caused by postzygotic HRAS and KRAS mutations. These mutations may predispose individuals to the development of secondary tumors in nevus sebaceous.
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Keratinocytic epidermal nevi are associated with mosaic RAS mutations.
J. Med. Genet.
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Activating RAS mutations in the germline cause rare developmental disorders such as Costello syndrome. Somatic RAS mutations are found in approximately 30% of human cancers. Keratinocytic epidermal nevi (KEN) represent benign congenital skin lesions arranged along Blaschkos lines. A subgroup of KEN is caused by hotspot oncogenic FGFR3 and PIK3CA mutations in mosaicism, but the majority lack these mutations.
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Indocyanine green-augmented diode laser therapy of telangiectatic leg veins: a randomized controlled proof-of-concept trial.
Lasers Surg Med
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Telangiectatic leg veins, which affect about 40-50% of adults, represent a frequent cosmetic rather than a medical problem. Besides sclerotherapy, various laser devices are common treatment options. However, complete clearance rates can only be achieved in a small number of patients.
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Impact of age and body site on adult female skin surface pH.
Dermatology (Basel)
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pH is known as an important parameter in epidermal barrier function and homeostasis.
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Activation of the PI3K/AKT pathway in Merkel cell carcinoma.
PLoS ONE
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Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with an increasing incidence. The understanding of the molecular carcinogenesis of MCC is limited. Here, we scrutinized the PI3K/AKT pathway, one of the major pathways activated in human cancer, in MCC. Immunohistochemical analysis of 41 tumor tissues and 9 MCC cell lines revealed high levels of AKT phosphorylation at threonine 308 in 88% of samples. Notably, the AKT phosphorylation was not correlated with the presence or absence of the Merkel cell polyoma virus (MCV). Accordingly, knock-down of the large and small T antigen by shRNA in MCV positive MCC cells did not affect phosphorylation of AKT. We also analyzed 46 MCC samples for activating PIK3CA and AKT1 mutations. Oncogenic PIK3CA mutations were found in 2/46 (4%) MCCs whereas mutations in exon 4 of AKT1 were absent. MCC cell lines demonstrated a high sensitivity towards the PI3K inhibitor LY-294002. This finding together with our observation that the PI3K/AKT pathway is activated in the majority of human MCCs identifies PI3K/AKT as a potential new therapeutic target for MCC patients.
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Fatty acids and vitamins generate singlet oxygen under UVB irradiation.
Exp. Dermatol.
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UVB radiation is already known as initiator and promoter of carcinogenesis in skin. UVB is well absorbed in proteins and DNA leading to products such as cyclobutane pyrimidine dimers. In contrast, UVA radiation generates reactive oxygen species such as singlet oxygen, which can initiate a variety of cellular damages and cellular signalling. It was the goal to investigate whether and to which extent UVB radiation is additionally able to cause oxidative damages via singlet oxygen. Potential endogenous photosensitizers such as vitamin B molecules or unsaturated fatty acids were irradiated in solution using monochromatic UVB radiation at 308 nm. Singlet oxygen was directly detected and quantified by its luminescence at 1270 nm. All investigated endogenous photosensitizers showed clear singlet oxygen signals with a quantum yield ranging from 5 to 40%. UVB radiation altered the photosensitizer molecules during irradiation yielding a change of absorption in the entire ultraviolet spectrum (280-400 nm). UVB irradiation of endogenous photosensitizers produced singlet oxygen that in turn changes the absorption of those molecules. Being an important prerequisite, the changed absorption may either reduce or increase singlet oxygen production. An increase in singlet oxygen generation may initiate a vicious cycle that has the potential to amplify UVB- or UVA-mediated effects in skin cells.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.