Table of Contents

Volume 1, Issue 4

  July/August 2009

  Pages 195 - 245

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EDITOR'S CORNER

Open Access Article

The skin is a fascinating endocrine organ

Jörg Reichrath
Pages 195 - 196
http://dx.doi.org/10.4161/derm.1.4.9653
PDF




REVIEWS

Open Access Article

Nanoparticles and their interactions with the dermal barrier

Marc Schneider, Frank Stracke, Steffi Hansen and Ulrich F. Schaefer
Pages 197 - 206
http://dx.doi.org/10.4161/derm.1.4.9501
Abstract | PDF

The dermal application of drugs is promising due to the ease of application. In this context nano-scale carrier systems were already evaluated in several studies with respect to the skin interaction and the impact on drug penetration. At the same time the upcoming production of engineered nano-scale materials requires a thorough safety evaluation. Drug delivery as well as risk assessment depends crucially on the ability of such carriers to overcome the skin barrier and reach deeper tissue layers. Therefore, the interaction of nanoparticles with skin and especially skin models is an intriguing field. However, the data obtained do not show a clear image on the effect of nano-carriers. Especially the penetration of such particles is an open and controversially discussed topic. The literature reports different results mainly on pig or murine skin showing strong penetration (pig and mouse) or the opposite. Looking only at the sizes of the particles also no conclusive picture can be obtained. Nevertheless, size is regarded to play an important role for skin penetration. Furthermore, the state of the skin influences penetration (hydration) and the mechanical stress is of outmost importance.

Open Access Article

In defense of the sun: An estimate of changes in mortality rates in the United States if mean serum 25-hydroxyvitamin D levels were raised to 45 ng/mL by solar ultraviolet-B irradiance


William B. Grant
Pages 207 - 214
http://dx.doi.org/10.4161/derm.1.4.9841
Abstract | PDF

Emerging scientific evidence strongly supports the beneficial role of vitamin D in reducing the risk of incidence and death from many chronic and infectious diseases. This study estimates increases in melanoma and nonmelanoma skin cancer mortality rates and decreases in chronic and infectious disease mortality rates in the United States from the standpoint of approximately doubling population doses of solar UVB to increase mean serum 25-hydroxyvitamin D levels from 16 ng/mL for black Americans and 25 ng/mL for white Americans to 45 ng/mL. The primary benefits are expected to come from reductions in cancer and cardiovascular diseases. Although a few thousand excess deaths per year might occur from melanoma and skin cancer, the avoided premature death rate could be near 400,000/year, with most of the avoided deaths coming late in life. While oral sources of vitamin D could be used instead of UVB or when UVB irradiance is not available, public health policies do not yet recommend the 3000-4000 IU/day required to raise serum 25-hydroxyvitamin D levels to the levels required for optimal health, which would be required before vitamin D fortification levels in food can be raised. Until then, moderate solar UVB irradiance remains an import source, and the health benefits greatly outweigh the risks.




REPORTS

Open Access Article

The possible roles of solar ultraviolet-B radiation and vitamin D in reducing case-fatality rates from the 1918–1919 influenza pandemic in the United States

William B. Grant and Edward Giovannucci
Pages 215 - 219
http://dx.doi.org/10.4161/derm.1.4.9063
Abstract | PDF

Deaths during the 1918–1919 influenza pandemic have been linked to both the influenza virus and secondary bacterial lung infections. Case fatality rates and percentage of influenza cases complicated by pneumonia were available from survey data for twelve United States locations in the 1918–1919 pandemic. This study analyzes case fatality rates and cases complicated by pneumonia with respect to estimated summertime and wintertime solar ultraviolet-B (UVB) doses as indicators of population mean vitamin D status. Substantial correlations were found for associations of July UVB dose with case fatality rates (r = -0.72, p = 0.009) and rates of pneumonia as a complication of influenza (r = -0.77, p = 0.005). Similar results were found for wintertime UVB. Vitamin D upregulates production of human cathelicidin, LL-37, which has both antimicrobial and antiendotoxin activities. Vitamin D also reduces the production of proinflammatory cytokines, which could also explain some of the benefit of vitamin D since H1N1 infection gives rise to a cytokine storm. The potential role of vitamin D status in reducing secondary bacterial infections and loss of life in pandemic influence requires further evaluation.

Open Access Article

Recurring mixed-type neurothekeoma of the face

Cornelia S.L. Müller, Wolfgang Tilgen, H. Kutzner and Claudia Pföhler
Pages 220 - 222
http://dx.doi.org/10.4161/derm.1.4.9442
Abstract | PDF

Background: Neurothekeomas are rare, benign neoplasms, typically occurring in younger patients with a remarkable predilection for the female population. The nomenclature and derivation of these tumors is controversial. The rarity of this unusual skin tumor in daily routine histopathologic findings prompted the following report.

Observation: We report a 17-year-old girl with an asymptomatic nodule at the inner angle of the left eye with slow progression in size within 12 months to 1 cm in diameter. Multiple treatments with laser surgery were performed and yielded no persistent remission of the tumor. Histopathologic examination revealed a non-encapsulated dermal tumor, composed of multiple, closely situated medium-sized nodules, separated by a myxoid collagen-rich stroma, without epidermal alteration. In summary, due to the histoarchitecture and immunoprofile of the tumor, a mixed-type cellular neurothekeoma was diagnosed.

Conclusion:
We think that it is important to be aware of these uncommon soft tissue lesions and the pitfalls of mixed-type neurothekeomas that often cause diagnostic problems. The aim of this report is to help to avoid misdiagnoses of malignant mesenchymal tumors with serious consequences, including extensive surgical therapy or radiation.

Open Access Article

Epidemiologic evidence for supporting the role of maternal vitamin D deficiency as a risk factor for the development of infantile autism


William B. Grant and Connie M. Soles
Pages 223 - 228
http://dx.doi.org/10.4161/derm.1.4.9500
Abstract | PDF

This study examines whether maternal vitamin D deficiency is a risk factor for infantile autism disease (IAD). We used epidemiologic data seasonal variation of birth rates and prevalence of IAD for cohorts born before 1985. For seven studies reporting spring-to-summer excess birth rates for IAD, the season progressed from broad near 30° N latitude, spring/summer in midlatitudes, to winter at the highest latitude. Also, using data from 10 studies, we found a strong effective latitudinal (related to wintertime solar ultraviolet B radiation) increase in IAD prevalence. These findings are consistent with maternal vitamin D deficiency’s being a risk factor for IAD, possibly by affecting fetal brain development as well as possibly by affecting maternal immune system status during pregnancy,.  Further investigation of this hypothesis is warranted.

Open Access Article

Leucocytoclastic vasculitis associated with acquired reactive perforating collagenosis: A diagnostic mimicry

Cornelia S.L. Müller, Wolfgang Tilgen and Knuth Rass
Pages 229 - 231
http://dx.doi.org/10.4161/derm.1.4.9555
Abstract | PDF

Reactive perforating collagenosis is a rare dermatosis, firstly described in 1967 and known to manifest as an inherited autosomal recessive form occurring in childhood and a sporadic, acquired form. There is no report of an association between perforating collagenosis and cutaneous vasculitis until now. The case presented shows the association of these two disease entities and discusses in detail histopathologic and clinical features, differential diagnoses and pathomechanisms of these entities.

Open Access Article

Activation of vitamin D receptor (VDR)- and peroxisome proliferator-activated receptor (PPAR)-signaling pathways through 1,25(OH)₂D₃ in melanoma cell lines and other skin-derived cell lines


Pit Sertznig, Markus Seifert, Wolfgang Tilgen and Jörg Reichrath
Pages 232 - 238
http://dx.doi.org/10.4161/derm.1.4.9629
Abstract | PDF

We have investigated expression of vitamin D receptor (VDR) and peroxisome proliferator-activated receptors (PPAR)a,d,g in primary cultured normal melanocytes (NHM), melanoma cell lines (MeWo, SK-Mel-5, SK-Mel-25, SK-Mel-28), a cutaneous squamous cell carcinoma cell line (SCL-1) and an immortalized sebocyte cell line (SZ95). LNCaP prostate cancer cells, MCF-7 breast cancer cells and embryonic kidney cells (HEK-293) were used as controls. VDR and PPAR mRNA were detected, quantitated and compared in these cell lines using real-time quantitative polymerase chain reaction (RTqPCR). The expression patterns of these nuclear receptors (NRs) varied strongly between the different cell lines according to their origin. PPARd and PPARg were less strongly expressed in the melanoma cell lines and in the other skin-derived cell lines as compared to the control cell lines. PPARa and VDR were stronger expressed in the 1,25(OH)₂D₃-sensitive melanoma cells (MeWo and in SK-Mel-28) than in the 1,25(OH)₂D₃-resistent melanoma cell lines (SK-Mel-5 and SK-Mel-25) or in NHM. Interestingly, VDR expression was increased by the treatment with 1,25(OH)₂D₃ in 1,25(OH)₂D₃-sensitive melanoma cells but not in 1,25(OH)₂D₃-resistent melanoma cell lines. 1,25(OH)₂D₃ increased the expression of PPARa in almost all cell lines analysed. Our results indicate a cross-talk between VDR- and PPAR-signaling pathways in various cell types including melanoma cells. Further investigations are required to investigate the physiological and pathophysiological relevance of this cross-talk. Because VDR- and PPAR-signaling pathways regulate a multitude of genes that are of importance for a multitude of cellular functions including cell proliferation, cell differentiation, immune responses and apoptosis, the provided link between VDR and PPAR may open important new perspectives for treatment and prevention of melanoma and other diseases.

Open Access Article

1,25-dihydroxyvitamin D3 protects human keratinocytes against UV-B-induced damage: in vitro analysis of cell viability/proliferation, DNA-damage and repair


Lea Trémezaygues, Markus Seifert, Wolfgang Tilgen and Jörg Reichrath
Pages 239 - 245
http://dx.doi.org/10.4161/derm.1.4.9705
Abstract | PDF

The skin is the only organ that has the capacity to photosynthesize the biological active vitamin D metabolite 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] from 7-dehydocholesterol (7-DHC), following exposure to ultraviolet (UV)-B irradiation. The aim of the present work was to investigate the capacity of 1,25(OH)₂D₃ to protect human keratinocytes (HaCaT) and squamous cell carcinoma cell lines (SCL-1) against the hazardous effects of UV-B irradiation. Human keratinocytes (HaCaT) and squamous cell carcinoma cell lines (SCL-1) were pretreated with 1,25(OH)₂D₃ over 48 hours and then irradiated once with UVB-radiation. We evaluated the results of several assays (colony-forming-unit-culture assay, WST-1-assay and crystal violet assay), comparing viability/proliferation in 1,25(OH)₂D₃-pretreated cells with controls that were pretreated with the carrier substance ethanol alone. Additionally, we analyzed the effects of 1,25(OH)₂D₃ on UV-induced DNA damage in HaCaT-keratinocytes by detection of cyclobutane pyrimidine dimers (CPDs) via dot blot analysis. We prove that 1,25(OH)₂D₃, in a concentration of 10^-7M, protects human keratinocytes (HaCaT) as well as squamous cell carcinoma cell lines (SCL-1) against the hazardous effects of UV-B-radiation (100J/cm²-1000J/cm²) in vitro. Moreover, we demonstrate that the number of CPDs induced in HaCaT-keratinocytes after irradiation with UV-B (100J/cm²-1000J/cm²) was decreased after pretreatment with 1,25(OH)₂D₃, as compared to carrier-treated controls. Analysis of the time course revealed that the elimination of UV-B-induced DNA-damage in HaCaT-keratinocytes occurs quicker when cells are pretreated with 1,25(OH)₂D₃ (as compared to controls). To put it in a nutshell, our data support the hypothesis that 1,25(OH)₂D₃ protects cultured human keratinocytes against the hazardous effects of UV-B radiation.