Table of Contents

Volume 4, Issue 1

  January/February/March 2012

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EDITOR'S CORNER

Open Access Article

The skin: A powerful hormone factory

Jörg Reichrath
Full Text | PDF




FOR DEBATE

Open Access Article

Does Rosuvastatin increase serum levels of 25-hydroxy-vitamin D?

Hartmut H. Glossmann and Mario Blumthaler
Abstract | Full Text | PDF

An observational study and a “clinical trial” seem to prove that rosuvastatin (but not fluvastatin) dramatically increases serum levels of 25-(OH)-D3 (three-fold above starting values). A critical analysis of the two publications, presented below, raises serious concerns. Conclusions from these two studies have already been drawn in the scientific literature.It is argued that claiming or believing in a “novel pleiotropic effect of rosuvastatin” may be misleading and premature.

Open Access Article

Statins and vitamin D: A hot topic that will be discussed for a long time

Bunyamin Yavuz and Derun Taner Ertugrul
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Open Access Article

The Statin D-lemma

Michael F. Holick
Full Text

Open Access Article

On the roles of solar UV irradiance and smoking on the diagnosis of second cancers after diagnosis of melanoma

William B. Grant
Abstract | Full Text | PDF

Several recent papers have reported standardized incidence ratios (SIRs) for second cancers after diagnosis of cutaneous malignant melanoma. This review divides the types of cancer into five types: (1) those for which UV-B (UVB) irradiance and vitamin D reduces risk; (2) those for which UVB/vitamin D reduces risk and smoking increases risk; (3) smoking related; (4) unknown UVB/vitamin D and smoking sensitivity; and (5) those for which UV irradiance increases risk. For those in category 1, SIRs were either significantly elevated or not significantly different from 1.0. For those in category 2, the SIR for kidney cancer was significantly elevated, whereas the SIRs for cervical, laryngeal and rectal cancer were significantly reduced. For those in category 3, all SIRs were significantly reduced. For those in categories 4 and 5, SIRs for all types except lip cancer were significantly elevated. A registry linkage study found significantly reduced SIRs for second cancers after diagnosis of nonmelanoma skin cancer in sunny countries but found increased SIRs in less sunny countries. The SIRs for second cancer for melanoma were elevated in both sunny and less sunny countries. This review concludes that sun exposure without sufficient vitamin D production may explain the elevated SIRs for vitamin D-sensitive cancers, whereas smoking—through production of skin elastosis, thereby reducing the risk of melanoma—probably explains the findings for smoking-related cancers. Thus, guidelines on UV irradiance should emphasize regular moderate UVB irradiance rather than avoidance for those who can tan.

Open Access Article

How do solar UV irradiance and smoking impact the diagnosis of second cancers after diagnosis of melanoma?: No answer yet

Marianne Berwick
Abstract | Full Text | PDF

It may be useful to look at the risk patterns for developing a second primary malignancy after a first primary melanoma diagnosis in order to understand the etiology and mortality due to melanoma. In this volume, WB Grant has proposed the interesting hypothesis that solar UV radiation and smoking may be inversely associated with the development of melanoma through the presence of dermal or solar elastosis. However, this association is inconsistent and may be explained by confounding by outdoor activity, physical exercise, obesity, diet and underlying immune or genetic factors.




REVIEW

Open Access Article

Dietary intervention in acne: Attenuation of increased mTORC1 signaling promoted by Western diet

Bodo Melnik
Abstract | Full Text

The purpose of this paper is to highlight the endocrine signaling of Western diet, a fundamental environmental factor involved in the pathogenesis of epidemic acne. Western nutrition is characterized by high calorie uptake, high glycemic load, high fat and meat intake, as well as increased consumption of insulin- and IGF-1-level elevating dairy proteins. Metabolic signals of Western diet are sensed by the nutrient-sensitive kinase, mammalian target of rapamycin complex 1 (mTORC1), which integrates signals of cellular energy, growth factors (insulin, IGF-1) and protein-derived signals, predominantly leucine, provided in high amounts by milk proteins and meat. mTORC1 activates SREBP, the master transcription factor of lipogenesis. Leucine stimulates mTORC1-SREBP signaling and leucine is directly converted by sebocytes into fatty acids and sterols for sebaceous lipid synthesis. Over-activated mTORC1 increases androgen hormone secretion and most likely amplifies androgen-driven mTORC1 signaling of sebaceous follicles. Testosterone directly activates mTORC1. Future research should investigate the effects of isotretinoin on sebocyte mTORC1 activity. It is conceivable that isotretinoin may downregulate mTORC1 in sebocytes by upregulation of nuclear levels of FoxO1. The role of Western diet in acne can only be fully appreciated when all stimulatory inputs for maximal mTORC1 activation, i.e., glucose, insulin, IGF-1 and leucine, are adequately considered. Epidemic acne has to be recognized as an mTORC1-driven disease of civilization like obesity, type 2 diabetes, cancer and neurodegenerative diseases. These new insights into Western diet-mediated mTORC1-hyperactivity provide a rational basis for dietary intervention in acne by attenuating mTORC1 signaling by reducing (1) total energy intake, (2) hyperglycemic carbohydrates, (3) insulinotropic dairy proteins and (4) leucine-rich meat and dairy proteins. The necessary dietary changes are opposed to the evolution of industrialized food and fast food distribution of Westernized countries. An attenuation of mTORC1 signaling is only possible by increasing the consumption of vegetables and fruit, the major components of vegan or Paleolithic diets. The dermatologist bears a tremendous responsibility for his young acne patients who should be advised to modify their dietary habits in order to reduce activating stimuli of mTORC1, not only to improve acne but to prevent the harmful and expensive march to other mTORC1-related chronic diseases later in life.




REPORTS

Open Access Article

Advanced glycation end products measured by skin autofluorescence in a population with central obesity

Corine den Engelsen, Maureen van den Donk, Kees J. Gorter, Philippe L. Salome´ and Guy E. Rutten
Abstract | Full Text | PDF

Accumulation of advanced glycation end products (AGEs) is enhanced by chronic hyperglycemia and oxidative stress and this process may contribute to the pathogenesis of vascular disease. Skin autofluorescence (AF), a measure of accumulation of AGEs in skin collagen, is associated with vascular disease in patients with diabetes.

Because central obesity enhances oxidative stress people with central obesity might already have increased accumulation of AGEs before diabetes or cardiovascular disease become manifest. To test this hypothesis, we compared the distribution of skin AF and its association with clinical and biochemical parameters in individuals with and without central obesity.

Skin AF was measured by a validated AGE Reader in 816 persons with and 431 persons without central obesity, aged 20–70 y.

Mean skin AF increased with age and smoking and was higher in centrally obese individuals compared with non-obese individuals (p = 0.001, after adjustment for age and smoking p = 0.13). Mean skin AF in the subgroups without central obesity and without other risk factors (n = 106), central obesity without other risk factors (n = 74) and central obesity with other risk factors (n = 742) was 1.63 ± 0.37, 1.74 ± 0.44 and 1.87 ± 0.43 AU, respectively (p for trend < 0.001, after adjustment for age and smoking p for trend = 0.12).

In the group with central obesity age, current smoking, alcohol consumption, waist circumference, creatinine clearance and hs-CRP were independently associated with skin AF (R² = 29.4%). Waist circumference hardly contributed to the explained variance. The relationship between waist circumference and skin AF is not as obvious as we hypothesized.

Open Access Article

Vitamin D and calcium status in urban children attending an ambulatory clinic service in the United Arab Emirates

Jaishen Rajah, Afrozul Haq and John M Pettifor
Abstract | Full Text | PDF

Background: Maintaining a normal vitamin D status is important for both skeletal and extra-skeletal health. Recent data show that vitamin D deficiency is endemic in women residing in the Arabian Gulf and is common in pregnant women and their newborns. The purpose of this study was to establish the vitamin D and calcium status of children in an urban ambulatory pediatric clinic in Abu Dhabi to determine for the prevalence of vitamin D deficiency in this cohort.

 

Methods: Patients were recruited prospectively from the pediatric outpatient clinic visits, if they were having blood taken for laboratory investigations other than those related to vitamin D and calcium status. The vitamin D status was compared between 4 age groups (0–0.9 y, 1–1.9 y, 2–7.9 y and 8 -14 y) using the following definitions: deficiency < 25 nmol/l, insufficiency 25–50 nmol/l and sufficiency > 50 nmol/l.

Results: A total of 183 children were included in the study. The percentage of females and males in the deficient range was 21% and 16% respectively, while 32% and 46% of females and males respectively were vitamin D sufficient. The highest prevalence of vitamin D deficiency occurred in the 8–14 y old age group with 31.2% being deficient.

Conclusions: The study highlights that in an ambulatory pediatric clinic population, peri-pubescent children are most at risk of vitamin D deficiency. This age group is often not considered in the discussion for the need for vitamin D supplementation. Serious consideration should be given to including vitamin D supplementation in a school public health program in the UAE.

Open Access Article

No evidence for induction of key components of the Notch signaling pathway (Notch-1, Jagged-1) by treatment with UV-B, 1,25(OH)₂D₃, and/or epigenetic drugs (TSA, 5-Aza) in human keratinocytes in vitro

Sandra Reichrath and Jörg Reichrath
Abstract | Full Text | PDF

Notch signaling is of high importance for growth and survival of various cell types. We now analyzed the protein expression of two key components of the Notch signaling pathway (Notch-1, Jagged-1) in spontaneously immortalized (HaCaT) and in malignant (SCL-1) human keratinocytes, using western analysis. We found that Notch-1 and its corresponding ligand Jagged-1 are expressed in both cell lines, with no marked change following UV-B treatment. Moreover, treatment of both cell lines before or after UV-B irradiation with 1,25-dihydroxyvitamin D₃, the biologically active form of vitamin D, and/or epigenetic modulating drugs (TSA; 5-Aza) did not result in a marked modulation of the protein expression of Notch-1 or Jagged-1. Under the experimental conditions of this study, treatment with 1,25(OH)₂D₃ protected human keratinocytes in part against the antiproliferative effects of UV-B-radiation. In conclusion, our findings do not point at a differential expression of these two key components of Notch signaling in non-malignant as compared to malignant human keratinocytes, indicating that alterations in their expression are not of importance for the photocarcinogenesis of human squamous cell carcinomas. Moreover, our findings do not support the hypothesis that modulation of Notch signaling may be involved in the photoprotective effect of 1,25-dihydroxyvitamin D₃, that we and others reported previously. Additionally, we demonstrate that epigenetic modulating drugs (TSA, 5-Aza) do not markedly modulate the expression Notch-1 or Jagged-1 in UV-B-treated human keratinocytes in vitro.

Open Access Article

When are laboratory tests indicated in patients with vitiligo?

Marina Rodriguez-Martin, Miguel Sáez, Nayra Merino de Paz, Patricia Contreras Ferrer, Mar Pestana Eliche, Beatriz Rodríguez-Martín and Antonio Noda Cabrera
Abstract | Full Text | PDF

Background: Vitiligo has been associated with multiple endocrine and immune conditions. Several laboratory tests have been assessed in this disease with controversial results.

 

Objective: The aim of this study is to analyze the levels autoantibodies, basal glycaemia, vitamin B12, folic acid and thyroid function and its association with the diagnosis and outcome of vitiligo patients through a case-control study.

Material and methods: This case-control study was performed on 196 consecutive patients with vitiligo referred to our Dermatology Department. As a control group, 160 healthy individuals without vitiligo or known history of immunologic/endocrine disease were included. Data were analyzed using the SPSS 17.0 statistical software package.

Results: Clinical, analytical and demographic data have been recorded. Our results showed that anti-thyroid peroxidase antibody and anti-parietal gastric cell antibody could be useful laboratory markers in a subpopulation of vitiligo patients. However, testing anti-nuclear antibody, anti-thyroglobulin antibody, folic acid and vitamin B12 seems to have limited clinical implication and diagnostic relevance in our routine clinical practice.

Limitations: This study addressed a selected population of vitiligo patients in Spain and may not generalize to different clinical settings or regions. The study of a wider sample would confirm these findings and allow a detailed analysis of the above factors as a function of the clinical subtype of vitiligo.

Conclusion: We have determined the more efficient serological markers to order in vitiligo patients. Our findings suggest that anti-thyroid peroxidase antibody and anti-parietal gastric cell could be useful tests for the characterization of specific subpopulations of vitiligo patients in terms of severity and co-morbidity, so their determination could have a prognostic value.

Open Access Article

Age and skin site related differences in steroid metabolism in male skin point to a key role of sebocytes in cutaneous hormone metabolism

Markus Haag, Tina Hamann, Alexandra E. Kulle, Felix G. Riepe, Thomas Blatt, Horst Wenck, Paul-Martin Holterhus and Reto Ivo Peirano
Abstract | Full Text | PDF

Hormone concentrations decline with aging. Up to now it was not clear, whether the decrease of hormone concentrations in blood samples are also present in cutaneous suction blister fluids, and whether skin from different anatomical sites shows different hormone concentrations.

 

Analysis of suction blister fluids and paired blood samples from young (mean 27.8 y) and old (mean 62.6 y) male subjects by UPLC-MS/MS showed that DHEA concentration in blood samples was age-dependently significantly reduced, but increased in suction blister fluids, while androstenedione behaved in an opposite manner to DHEA. Testosterone decreased age-dependently in blood samples and in suction blister fluids. Regarding skin sites, DHEA was lower in samples from upper back compared with samples from the forearm. In contrast, the concentrations of androstenedione and testosterone were higher in samples from upper back.

In vitro analyses showed that SZ95 sebocytes, but neither primary fibroblasts nor keratinocytes, were able to use DHEA as precursor for testosterone biosynthesis, which was confirmed by expression analysis of 3β-hydroxysteroiddehydrogenase in skin biopsies.

In conclusion, we show an inverse pattern of DHEA and androstenedione concentrations in blood vs. suction blister fluids, highlighting age-dependent changes of dermal testosterone biosynthesis, and a stronger metabolism in young skin. Furthermore, sebocytes play a central role in cutaneous androgen metabolism.

Open Access Article

Hair loss and hyperprolactinemia in women

Gerhard Lutz
Abstract | Full Text | PDF

In the literature of the past 30 years there are only some publications concerning with hair loss and hyperprolactinemia in women. Therefore, the relevance of hyperprolactinemia was evaluated in 40 women with diffuse alopecia.

 

Hair loss was assessed by clinical appearance and the pluck trichogram. 82.5% of the female patients had diffuse hair loss and 17.5% had androgenetic alopecia.

The highest prolactin values measured were 1390 ng/ml and 255 ng/ml. Six patients had values between 150–80.4 ng/ml and 10 between 79.1–51.7 ng/ml. All others had prolactin values below 50 ng/ml. Fifteen untreated patients with elevated prolactin levels could be followed up. Without any prolactin-inhibiting drugs, reductions and normalizations beside moderate fluctuations could be detected.

Thyroid-specific diagnostics showed in 95% of the patients a normal thyroid function. 2.5% had a slight hyperthyreoidism and 2.5% had a slight hypothyreoidism. No female patient had clinical signs of androgenization and the determined androgens testosterone, androstendione and dihydroepiandrostendione were in the normal range.

According to these results, moderate elevated prolactin levels in association with diffuse or androgenetic hair loss can be neglected as causative for the hair loss, because there is no evidence that they have an influence to the pattern, the extent or the duration of the hair loss. These results are supported by investigations of other authors who described only in high doses of prolactin an inhibiting effect on human hair follicles in vitro. Nevertheless, moderate constantly elevated prolactin levels should induce further diagnostics to exclude a prolactin-producing tumor of the pituitary gland.

Open Access Article

Vitamin D-insufficiency: An estimate of the situation in Germany

Johann Diederich Ringe and Christoph Kipshoven
Abstract | Full Text | PDF

Background: Vitamin D insufficiency is increasingly recognized as an important risk factor in the pathogenesis of falls and fractures and may increase the risk of other diseases. The aim of this study was to obtain information about the vitamin D supply from a representative cohort of the German population.

Methods: 264 General practitioners participated in the DeViD-Trial (D-vitamin in Deutschland) by taking blood samples from their consenting daily ambulant patients regardless of the actual reason for consultation. In these blood samples vitamin D [25(OH)D] and other related parameters were measured at a central laboratory. The patients filled in a simple questionnaire (i.e., age, sex, etc.). The trial was performed between February 26 and May 25, 2007.

Results: Laboratory and personal data were documented for 1343 individuals (615 men, 728 women). The age distribution ranged from 20 to 99 y, the mean age of the whole cohort was 57.6 y (men 58.2, women 57.2). The mean 25-OH-D-value for the whole cohort was 16.2 ng/ml (range: 6.0 to 66.8, median 14.1 ng/ml). Ten percent of the patients had 25(OH)D-values below 7 ng/ml, 65% below 20 ng/ml and 92% showed values below 30 ng/ml.

In the more recent literature, 25(OH)D values below 30 ng/ml are regarded as sub-optimal for bone, muscle and general health. Correspondingly it can be stated that in this representative population there is a high prevalence of moderate to severe vitamin D-insufficiency regardless of young or old age.