[Sun protection factor 50+ : Pro and contra]. / Lichtschutzfaktor 50+ : Pro und Kontra.

The use of sunscreens with sun protection factors beyond 50 is controversial. In order to avoid misleading the consumer, several countries have already decided not to declare SPF beyond 50 on sunscreen products. Arguments against high SPF include the following: the risk of imbalanced protection, which could increase the risk of damage caused by longer-wave ultraviolet radiation; imparting a false sense of safety, which could lead to the extension of sun exposure times; health risks from higher concentrations of filter substances; and the only marginally higher blockade provided by high SPF sunscreens. On the other hand, it has been realized that the functional SPF of sunscreens remains far behind the declared SPF in the practical application and, therefore, the use of higher SPF in sensitive individuals and during strong UV exposure could make sense.

The hand eczema proteome: imbalance of epidermal barrier proteins.

BACKGROUND: Chronic hand eczema (CHE) is a common skin disease with a high socioeconomic impact. While some light has been shed on the genetic factors that predispose individuals to the disease, little is known about its actual pathogenesis. OBJECTIVES: We aimed to carry out a systematic and comprehensive analysis of the differential protein expression in CHE using modern mass spectrometry. METHODS: We performed liquid chromatography with tandem mass spectrometry analyses and label-free quantification to analyse the proteomic profile of palmar skin from 12 individuals (six patients with hand eczema and six healthy volunteers). Immunohistochemistry of the palmar skin from seven different patients with hand eczema and seven different healthy volunteers was performed in a second step. RESULTS: With this method we were able to identify 185 candidate proteins with a significantly different abundance in the hand eczema samples. Among them we found several barrier proteins: filaggrin (FLG), FLG-2 and hornerin were all downregulated in the hand eczema samples, as were the desquamation-related enzymes kallikrein-related peptidase (KLK)5 and KLK7 and cystatin E/M. The antimicrobial peptides S100A7 and S100A8/A9 and the small proline-rich protein 2B and S100A11 were upregulated in the diseased skin. Immunohistochemistry confirmed these findings. CONCLUSIONS: Our results corroborate the assumption that skin barrier dysfunction plays an essential role in the pathogenesis of CHE.

Smoking is associated with combined allergic and irritant hand eczema, contact allergies and hyperhidrosis.

BACKGROUND: The pathogenesis of chronic hand eczema (CHE) is multifactorial. Certain life-style factors have been suggested as potential triggers of the disease, among them tobacco smoking. However, the few studies addressing the influence of smoking on CHE have been more or less limited to occupational hand eczema. OBJECTIVE: The aim of our study was to investigate the association of smoking status with clinical features like contact sensitization, irritant exposure, atopy and hyperhidrosis in a thoroughly characterized cohort of CHE patients. METHODS: A total of 153 patients with CHE underwent clinical examination and an interview about their history and course of disease. RESULTS: Significantly more smokers suffered from combined allergic and irritant hand eczema (25/86) than non-smokers (7/67; P < 0.05). Nickel sensitization and palmar hyperhidrosis tended to be more frequent among smokers than among non-smokers (nickel: 17/86 smokers, 6/67 non-smokers; hyperhidrosis: 21/84 smokers, 8/64 non-smokers). Among the smoking CHE patients with palmar hyperhidrosis, a significant proportion had contact allergies relevant contact allergies (16/21, P < 0.05). CONCLUSION: Our results reveal a predominance of smokers among patients with combined allergic and irritant hand eczema as well as with hyperhidrosis and relevant contact sensitizations.

Treatment of cutaneous T-cell lymphoma with oral alitretinoin.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is a potentially life-limiting malignant disease. Treatment strategies in CTCL aim at disease control and remission with the lowest possible side-effects. OBJECTIVE: Recent reports suggest that the new vitamin A derivative alitretinoin might be a well-tolerated treatment option. METHODS: We analysed the files of 11 CTCL patients with mycosis fungoides (n = 10) or Sézary syndrome (n = 1), who were treated with oral alitretinoin alone or in combination with standard treatment based on individual off-label treatment decisions. Patients had been monitored every 4-8 weeks with skin examination and laboratory analyses. RESULTS: Ten of 11 patients (90.9%) showed a marked improvement of their CTCL skin lesions and no progress of the disease during treatment with alitretinoin, one patient showed no response to the treatment (9.1%). Four of the responding patients (40.0%) had a complete response and 6 (60.0%) had a partial response. Average time to response was 2.5 months. Duration of treatment varied depending on whether patients had reached complete or partial remission. In general, alitretinoin was well tolerated. One of 11 patients developed high non-fasting average serum cholesterol (>300 mg/dL) and 1/11 a mean non-fasting triglyceride value >500 mg/dL. In 3/11 patients, thyroid-stimulating hormone declined without clinical symptoms during treatment, with one of the patients also showing a decreased thyroxin level. CONCLUSION: In our group of CTCL patients we noticed a low rate of side-effects and an overall good clinical response to treatment with alitretinoin. Further studies are required to substantiate this early clinical observation.

Silencing of the cell cycle checkpoint gene 14-3-3σ in basal cell carcinomas correlates with reduced expression of IKK-α.

BACKGROUND: 14-3-3σ is down-regulated in a large proportion of basal cell carcinomas (BCC). IkappaB kinase α (IKK-α), one of the two catalytic subunits of the IKK complex involved in NF-kappaB-activation, also functions as a modulator of epidermal development and differentiation. Down-regulation of IKK-α causes hyperplasia and promotes skin cancer. IKK-α has been found to regulate the expression of 14-3-3σ by shielding its promoter from hypermethylation and thereby preventing its silencing in mouse keratinocytes. OBJECTIVES: To evaluate the potential role of IKK-α in the silencing of 14-3-3σ in basal cell carcinoma. MATERIALS AND METHODS: Expression of 14-3-3σ and IKK-α was studied by immunohistochemistry in 33 sporadic BCCs and 26 BCCs from patients with basal cell nevus syndrome (BCNS). RESULTS: Marked reduction or absence of 14-3-3σ was found in 24 (92%) BCCs from BCNS patients, and in 29 (88%) sporadic BCCs. Marked reduction or absence of IKK-α was found in 22 (85%) BCCs from patients with BCNS, and in 27 (82%) sporadic BCCs. Expression levels for 14-3-3σ and IKK-α correlated positively in 92% of BCCs from BCNS patients, and in 85% of sporadic BCCs. CONCLUSIONS: Our findings suggest that down-regulation of IKK-α is required for 14-3-3σ promoter methylation and silencing in the pathogenesis of BCC. Besides, our observation that 14-3-3σ silencing is also frequently found in BCC from patients with BCNS suggests a possible link between the sonic hedgehog/patched and 14-3-3σ/IKK-α pathways.

Efficacy of bath psoralen plus ultraviolet A (PUVA) vs. system PUVA in psoriasis: a prospective, open, randomized, multicentre study.

BACKGROUND: Plaque psoriasis is an inflammatory disease affecting approximately 2% of the population. The clinical hallmarks of psoriasis are sharply demarcated, erythematous plaques with thick scales. Photochemotherapy (psoralen plus ultraviolet A, PUVA) is one of the most effective therapies of psoriasis. The photosensitizer 8-methoxypsoralen (8-MOP) can be applied either orally (system PUVA) or topically in a warm water bath (bath PUVA). OBJECTIVES: To compare bath PUVA and system PUVA in the treatment of plaque psoriasis. METHODS: This was a randomized, open, prospective, multicentre trial. We included 74 patients with moderate-to-severe plaque psoriasis during a 6-week treatment and a 4-week follow-up period. Of the patients enrolled in the study, 38 received bath PUVA and 36 system PUVA. RESULTS: Both treatment modalities significantly reduced the median Psoriasis Area and Severity Index (PASI) score in the intention-to-treat population. Within 6 weeks bath PUVA reduced the median PASI by 74% (16·4 to 4·2) while system PUVA did so by 62% (15·3 to 5·8). The difference between the two modalities was not significant with regard to treatment efficacy (P = 0·389). CONCLUSION: There is no difference between bath PUVA and system PUVA in the treatment of psoriasis.

Treatment of Darier disease with oral alitretinoin.

Darier disease (DD) is an autosomal dominant skin disease. Treatment is often difficult and unsatisfactory because of the chronic nature of the condition and the irritant potential of various therapeutic agents. Systemic vitamin A derivatives such as acitretin and isotretinoin are the treatment of choice, but their use is often limited by class-specific side-effects. Alitretinoin (9-cis-retinoic acid), has antiproliferative and anti-inflammatory potential, and is licensed for the systemic treatment of chronic hand eczema in a number of countries. Unlike acitretin, alitrenoin requires contraception in women of childbearing age to be extended for only 1 month after the end of treatment. There is evidence that alitretinoin might be a well-tolerated alternative for the systemic treatment of various retinoid-responsive skin diseases. We present two cases of women with refractory DD successfully treated with alitretinoin without marked side-effects, who both obtained near-complete remission of their skin lesions.

Knowledge of sexually transmitted HPV infection, genitoanal warts, cancer and their prevention among young females after vaccine introduction in Germany.

BACKGROUND: Sexually transmitted human papillomavirus (HPV) high-risk types cause carcinoma and low-risk types lead to warts of genitoanal area. Since the HPV vaccine has been introduced, awareness of HPV infection, prevention and health-related behaviour have not been studied in a large sample of young women in Germany. OBJECTIVES: Assessment of awareness and health-related behaviour regarding HPV infection and prevention among young German females. METHODS: In 2010, a postal cross-sectional survey was conducted with a random representative sample size (n = 2000) of females aged 19-35 attending Germany's largest (comprehensive) university, which was designed to obtain data about socio-demographics, the awareness of sexually transmitted HPV, genitoanal neoplasms and their prevention, HPV vaccine, immunisation and cervical cancer screening. RESULTS: Of the 547 (27.3%) participants, 69.1% had heard of HPV, 62.5% were aware of the vaccine, 14.4% were vaccinated and 6.9% reported a history of sexually transmitted infection, including HPV (2.7%). The HPV-related knowledge among those who had heard of it was high (75.1-99.7%), except of that HPV affects men (52.9%) and HPV's causative role in genital (54.2%) and anal (35.6%) warts, and smoking (11.3%) as an HPV risk factor. The lower HPV knowledge score (

IgE-mediated hypersensitivity reactions to cannabis in laboratory personnel.

BACKGROUND: There have been sporadic reports of hypersensitivity reactions to plants of the Cannabinaceae family (hemp and hops), but it has remained unclear whether these reactions are immunologic or nonimmunologic in nature. OBJECTIVE: We examined the IgE-binding and histamine-releasing properties of hashish and marijuana extracts by CAP-FEIA and a basophil histamine release test. METHODS: Two workers at a forensic laboratory suffered from nasal congestion, rhinitis, sneezing and asthmatic symptoms upon occupational contact with hashish or marijuana, which they had handled frequently for 25 and 16 years, respectively. Neither patient had a history of atopic disease. Serum was analyzed for specific IgE antibodies to hashish or marijuana extract by research prototype ImmunoCAP, and histamine release from basophils upon exposure to hashish or marijuana extracts was assessed. Results were matched to those of 4 nonatopic and 10 atopic control subjects with no known history of recreational or occupational exposure to marijuana or hashish. RESULTS: Patient 1 had specific IgE to both hashish and marijuana (CAP class 2), and patient 2 to marijuana only (CAP class 2). Controls proved negative for specific IgE except for 2 atopic individuals with CAP class 1 to marijuana and 1 other atopic individual with CAP class 1 to hashish. Stimulation of basophils with hashish or marijuana extracts elicited histamine release from basophils of both patients and 4 atopic control subjects. CONCLUSIONS: Our results suggest an IgE-related pathomechanism for hypersensitivity reactions to marijuana or hashish.

The pRb-related protein p130 is a possible effector of transforming growth factor beta 1 induced cell cycle arrest in keratinocytes.

Transforming growth factor beta 1 (TGF-beta 1) is known to inhibit epithelial cell growth by inducing a G1 cell cycle arrest. We have studied the effect of TGF-beta 1 on protein binding to a transcription factor E2F consensus element in extracts from early passage human keratinocytes (HFKs) and a permanent human keratinocyte cell line (HaCaT). Treatment of these cells with TGF-beta 1 resulted in the formation of a DNA binding complex between the pRb-related protein p130 and E2F. Formation of the E2F-p130 complex correlated with inhibition of cell cycle progression in G1 and suppression of the E2F-regulated cdc2 gene. While p130 mRNA and protein levels were not influenced by TGF-beta 1, the activity of cyclin-dependent kinase 2 (Cdk2) towards p130 in vitro was inhibited. The results identify p130 as a downstream target of TGF-beta 1 and a possible mediator of the G1 cell cycle arrest.

A complex between E2F and the pRb-related protein p130 is specifically targeted by the simian virus 40 large T antigen during cell transformation.

The p130 protein is a recently cloned member of the retinoblastoma protein family. We show here that transformation of NIH3T3-L1 fibroblasts (L1 cells) by the simian virus 40 large T antigen (LTAg) depends on the disruption of DNA binding complexes between transcription factor E2F and p130. LTAg binds to the pocket region of p130 in vivo and disrupts the E2F-p130 complexes. E2F-p130 complexes are present only in quiescent L1 cells and disappear at the G1/S phase boundary concomitantly to induction of DNA synthesis and expression of the E2F-regulated cdc2 gene. p130 is a substrate of cyclin-dependent kinase 2 (Cdk2) in vitro and associates with a Cdk in vivo which is activated upon serum stimulation in late G1. Overexpression of p130 inhibits cdc2 promoter activity and entry of quiescent L1 cells into S phase. The results demonstrate that p130 is negative regulator of cell cycle progression which is specifically targeted by LTAg during cell transformation.

Ultraviolet B irradiation-induced G2 cell cycle arrest in human keratinocytes by inhibitory phosphorylation of the cdc2 cell cycle kinase.

In response to genotoxic stress, cell cycle progression can be arrested at certain checkpoints which serve to maintain genomic integrity. We have investigated the mechanism of ultraviolet B (UVB) irradiation-induced cell cycle arrest in normal human keratinocytes and in the HaCaT keratinocyte cell line which carries mutant p53 tumour suppressor protein. While only normal keratinocytes showed a delay in G1 following sublethal UVB irradiation both cell types exhibited prolonged G2 arrest attributable to rapid inhibition of cyclin B-associated cdc2 kinase activity. This inhibition coincided with increased tyrosine phosphorylation of cdc2 and was reversed by the cdc25C phosphatase in vitro. The data indicate that UVB-induced G2 arrest in mammalian cells is mediated by inhibitory tyrosine phosphorylation of cdc2 and acts as a defense mechanism against DNA damage irrespective of the cells' p53 status.

Transcriptional and posttranscriptional regulation of human androgen receptor expression by androgen.

Autoregulation is a control mechanism common to several proteins of the steroid/thyroid hormone receptor superfamily. In this work, the effect of androgens and antiandrogens on the expression of the human androgen receptor (hAR) in prostate and breast cancer cell lines was studied. Northern blot analysis revealed a decrease in hAR steady state RNA levels in LNCaP cells by 3.3 nM of the synthetic androgen mibolerone. Maximal down-regulation of hAR RNA to 30% of control levels occurred 48 h after hormone addition. T47D breast cancer cells showed a similar effect with mibolerone, while hAR expression in normal skin fibroblasts did not respond to androgen treatment. As shown by nuclease S1 analysis, hAR transcripts initiate at three principal start sites, all of which are equally sensitive to androgen. Steroidal as well as nonsteroidal antiandrogens were capable of partially antagonizing androgen-mediated hAR RNA down-regulation in LNCaP and T47D cells, while not exerting a significant effect when administered alone. While hAR RNA stability was increased by hormone, nuclear run-on analysis revealed a 4-fold reduction of hAR gene transcription 96 h after androgen treatment. Although decreased hAR RNA levels did not coincide with a parallel decrease in AR protein levels, analysis of androgen-inducible reporter constructs demonstrated that prolonged androgen administration to cells results in a progressively impaired sensitivity of the intracellular androgen response mechanism. These results show that prolonged androgen exposure leads, besides its effect on hAR RNA levels, to functional inactivation of the AR. Thus, in vivo, posttranslational control of AR activity appears to be a novel mechanism of negative autoregulation of androgen effects on gene expression.