Reduction in ultraviolet B light–induced erythema by oxymetazoline and brimonidine is mediated by different α‐adrenoceptors

When applied topically, oxymetazoline and brimonidine reduce the persistent facial erythema of rosacea; this effect is mediated by cutaneous vasoconstriction induced by postsynaptic activation of α‐adrenoceptors. We investigated the α‐adrenergic pharmacology of oxymetazoline and brimonidine. Functional activity on α‐adrenoceptors was evaluated in vitro in HEK293 cells stably expressing single receptor subtypes using a fluorometric imaging plate reader Ca²⁺ influx assay. Oxymetazoline was an α₁‐adrenoceptor agonist with partial α₂‐adrenoceptor activity, whereas brimonidine was a highly selective full α₂‐adrenoceptor agonist. In vivo pharmacology was investigated in a mouse model of ultraviolet B light (UVB)‐induced skin erythema. To selectively inhibit α‐adrenoceptor subtypes, mice were injected with prazosin (an α₁‐selective antagonist) or rauwolscine (an α₂‐selective antagonist) following UVB exposure. Oxymetazoline cream 1.0%, brimonidine gel 0.33% or vehicle control was applied topically, and erythema was measured using a chromameter. Oxymetazoline and brimonidine reduced UVB–induced erythema compared with vehicle control (P < .01). The effect of oxymetazoline was impaired in prazosin‐pretreated but not rauwolscine‐pretreated mice. Conversely, the effect of brimonidine was impaired in rauwolscine‐pretreated but not prazosin‐pretreated mice. These data suggest that while oxymetazoline and brimonidine produce cutaneous vasoconstriction, they do so through different α‐adrenergic mechanisms, with oxymetazoline primarily acting via α₁‐adrenoceptors and brimonidine acting via α₂‐adrenoceptors.     

Treatment of moderate and severe adult chronic atopic dermatitis with narrow‐band UVB and the combination of narrow‐band UVB/UVA phototherapy

The phototherapy is a safe and effective technique for the treatment of adult patients with atopic dermatitis (AD). The treatment of chronic forms of the disease is most often done with narrow‐band UVB (NB‐UVB). There also exist effective phototherapy options against the AD. The aim of this study was to asses if the combination of NB‐UVB with UVA was more effective than the treatment with only NB‐UVB against adult chronic AD. We carried out a prospective and observational study. Adult patients with chronic AD with more than 50% of the total body surface area affected (TBSA) were included. The affected TBSA was calculated using the so‐called “rule of nines.” Patients with a clearance rate >75% of the initial affected TBSA or complete clearance rate were considered as complete response (CR). An analogue scale from 0 to 10 was used to measure the improvement grade of the pruritus. The treatments were repeated three times a week. The initial doses of NB‐UVB and UVA were determined by patient's phototype. The treatments were performed using a phototherapy booth (UV7002, Walmann, Villingen‐Schwenningen, Germany^®) with TL01 and UVA fluorescent lamps. Statistical analysis was performed with SPSS^® (IBM, New York, NY) for Windows 21.0. A total of 26 patients with adult chronic AD were included in the study, 16 patients were treated with UVB‐BE and 10 patients with the combined treatment option NB‐UVB/UVA. The mean value of cumulative doses and the mean number of performed treatments were similar between both groups of patients (p > 0.05). The mean value of duration of response was significantly higher in the patients treated only with NB‐UVB, 101 versus 6.8 months (p ≥ 0.05). No differences were observed for the patients that showed complete response (p = 0.42) and in the analogue scale of pruritus (p > 0.005). In our study, the patients treated with the combination of NB‐UVB and UVA were similar to the patient that were only treated with NB‐UVB e. Further prospective and controlled studies have to be performed in order to determine the dosing regimens of phototherapy in adult patients with AD.     

Baicalein inhibits matrix metalloproteinase 1 expression via activation of TRPV1‐Ca‐ERK pathway in ultraviolet B–irradiated human dermal fibroblasts

Increased matrix metalloproteinase 1 (MMP‐1) expression is a feature of photo‐aged skin. We investigated the effects of baicalein and sulphoraphane on ultraviolet B (UVB) irradiation–induced MMP‐1 expression and apoptosis using human dermal fibroblasts. UVB irradiation not only increased MMP‐1 expression, but also caused apoptosis. Both baicalein and sulphoraphane protected cells from UVB irradiation–induced apoptosis, but only baicalein inhibited MMP‐1 expression. UVB irradiation activated 12‐lipoxygenase, and its product, 12‐hydroxyeicosatetraenoic acid, activated TRPV1 channels. The resulting UVB irradiation–induced Ca²⁺ increase was blocked by the 12‐lipoxygenase inhibitor baicalein and the TRPV1 blocker capsazepine, but not by the Nrf2 inducer sulphoraphane. UVB irradiation also increased ROS generation and decreased Nrf2 protein levels. UVB irradiation–induced MMP‐1 expression was blocked by the Ca²⁺ chelator BAPTA, by capsazepine and by TRPV1 silencing. However, induction was unaffected by the antioxidant N‐acetylcysteine. ERK phosphorylation and JNK phosphorylation were induced by UVB irradiation, but only ERK phosphorylation was Ca²⁺ sensitive. Increased MMP‐1 expression was blocked by PD98059, but not by SP600125. Thus, increased MMP‐1 expression is mediated by increased cytosolic Ca²⁺ and ERK phosphorylation. UVB irradiation–induced ROS generation is also Ca²⁺ sensitive, and UVB irradiation–induced apoptosis is caused by increased ROS. Thus, baicalein, by blocking the UVB irradiation–induced cytosolic Ca²⁺ increase, protects cells from UVB irradiation–induced MMP‐1 expression and apoptosis. In contrast, sulphoraphane, by decreasing cellular ROS, protects cells from only UVB‐induced apoptosis. Thus, targeting 12‐lipoxygenase may provide a therapeutic approach to improving the health of photo‐aged human skin.     

NADPH oxidase is a novel target of delphinidin for the inhibition of UVB‐induced MMP‐1 expression in human dermal fibroblasts

We investigated the reported antiphotoaging effects of the major anthocyanidin delphidin and sought to identify its specific molecular target during UVB‐induced MMP‐1 expression. Delphinidin treatment significantly inhibited UVB‐induced MMP‐1 expression in primary cultured human dermal fibroblasts (HDF), an effect associated with the suppression of MKK4‐JNK1/2, MKK3/6‐p38 and MEK‐ERK1/2 phosphorylation. Further investigation revealed that delphinidin significantly inhibited UVB‐induced ROS production and NOX activity. Interestingly, the inhibitory effect of delphinidin on UVB‐induced NOX activity was stronger than that of apocynin, a pharmaceutical NOX inhibitor. Fractioned cell analysis results using a Western blot assay showed that this effect occurred through the inhibition of UVB‐induced P47^phox (a NOX subunit) translocation from the cytosol to the membrane. Pull down assays demonstrated that delphinidin binds directly to P47^phox in vitro. Collectively, our results suggest that delphinidin targets NOX, resulting in the suppression of UVB‐induced MMP‐1 expression in human dermal fibroblasts.     

Loss of INK4a/Arf gene enhances ultraviolet radiation‐induced cutaneous tumor development

The CDKN2A locus encodes for tumor suppressor genes p16^INK4a and p14^Arf which are frequently inactivated in human skin tumors. The purpose of this study was to determine the relationship between loss of INK4a/Arf activity and inflammation in the development of ultraviolet (UV) radiation‐induced skin tumors. Panels of INK4a/Arf^‐/? mice and wild‐type (WT) mice were treated with a single dose of UVB (200 mJ/cm²). For long‐term studies, these mice were irradiated with UVB (200 mJ/cm²) three times weekly for 30 weeks. At the end of the experiment, tissues were harvested from mice and assayed for inflammatory biomarkers and cytokines. A single dose of UVB resulted in a significant increase in reactive oxygen species (ROS) and 8‐dihydroxyguanosine (8‐oxo‐dG) lesions in INK4a/Arf^?/? mice compared to WT mice. When subjected to chronic UVB, we found that 100% of INK4a/Arf^?/‐ mice had tumors, whereas there were no tumors in WT controls after 24 weeks of UVB exposure. The increase in tumor development correlated with a significant increase in nuclear factor (NF)‐κB, cyclooxygenase‐2 (COX‐2), prostaglandin E₂ (PGE₂) and its receptors both in UVB‐exposed skin and in the tumors. A significant increase was seen in inflammatory cytokines in skin samples of INK4a/Arf^‐/‐ mice following treatment with chronic UVB radiation. Furthermore, significantly more CD11b⁺Gr1⁺ myeloid cells were present in UVB‐exposed INK4a/Arf^‐/‐ mice compared to WT mice. Our data indicate that by targeting UVB‐induced inflammation, it may be possible to prevent UVB‐induced skin tumors in individuals that carry CDKN2A mutation.     

P38 and JNK signal pathways are involved in the regulation of phlorizin against UVB‐induced skin damage

Phlorizin is well known to inhibit sodium/glucose cotransporters in the kidney and intestine for the treatment of diabetes, obesity and stress hyperglycaemia. However, the effects of phlorizin against ultraviolet B (UVB) irradiation and its molecular mechanism are still unknown. We examined the effects of phlorizin on skin keratinocyte apoptosis, reactive oxygen species (ROS) production, pro‐inflammatory responses after UVB irradiation and the changes of some signal molecules by in vitro and in vivo assay. We observed that phlorizin pretreatments inhibited HaCaT cell apoptosis and overproduction of ROS induced by UVB. Phlorizin also decreased the expression of UVB‐induced pro‐inflammatory cytokines, such as interleukin‐1 beta (IL‐1β), interleukin‐6 (IL‐6) and interleukin‐8 (IL‐8) at the mRNA level. Topical application of phlorizin on UVB‐exposed skin of nude mice prevented the formation of scaly skin and erythema, inhibited the increase of epidermal thickness and reduced acute inflammation infiltration in skin. Additionally, PCR, Western blot and immunohistochemical data showed that phlorizin reversed the overexpression of cyclooxygenase‐2 (Cox‐2) induced by UVB irradiation both in vitro and in vivo. The activation of p38 and JNK mitogen‐activated protein kinases (MAPK) after UVB irradiation was also inhibited by phlorizin. These findings suggest that phlorizin is effective in protecting skin against UVB‐induced skin damage by decreasing ROS overproduction, Cox‐2 expression and the subsequent excessive inflammation reactions. It seemed that p38 and JNK MAPK signal pathways are involved in the regulation of the protective function of phlorizin.     

A new therapeutic option for facial seborrhoeic dermatitis: indole‐3‐acetic acid photodynamic therapy

Background Indole‐3‐acetic acid (IAA) is a newly introduced photosensitizer of photodynamic therapy (PDT) for acne, presenting sebum‐reducing, anti‐inflammatory and antimicrobial activity. Objective This study was designed to evaluate the efficacy and safety of IAA‐PDT in the treatment of facial seborrhoeic dermatitis. Method In this prospective, single‐blinded, 6‐week trial, 23 patients with facial seborrhoeic dermatitis were treated with IAA‐PDT with green light (520 nm) three times with 1‐week intervals. Patients were evaluated at baseline, week 1, 2, 3 and week 6 (3 weeks after last treatment). Efficacy was determined by Seborrhoeic dermatitis Area and Severity Index (SASI), patient’s assessment of the symptoms (4‐point scale of itchiness, burning, erythema, scale and tightness), sebum secretion rate (measured with Sebumeter^®), Erythema Index (EI, measured with Mexameter^®) and physician’s photographic assessment. Safety was evaluated by questionnaire at each visit. Result For the 22 subjects completing the trial, SASI and total symptom significantly improved at week 2, which lasted until week 6. Sebum excretion was significantly reduced at week 2 and stayed reduced until week 6. EI presented continuous reduction throughout the study. Photographic assessment showed significant improvement at each visit. The procedure was painless, and no adverse event was observed during and after the treatment. Conclusion IAA‐PDT is a safe and effective therapeutic option for facial seborrhoeic dermatitis.     

Sunscreens containing the broad-spectrum UVA absorber, Mexoryl SX, prevent the cutaneous detrimental effects of UV exposure: a review of clinical study results

Background: UVA exposure of human skin mainly produces reactive oxygen species (ROS) leading to DNA, cell and tissue damage. It alters immune function, pigmentation and it is certainly responsible for a large part of photoaging changes. Moreover UVA is implicated in the etiology of several photodermatoses. As a consequence, to provide adequate protection, sunscreens or skin care products for daily use protective products need UVA absorbers combined with UVB ones. Aim: To assess the efficacy of sunscreens containing a broad‐spectrum UVA absorber the Mexoryl^® SX or ecamsule and to compare formulations with and without it through a large number of clinical studies in human volunteers and patients. Methods: The following assessments were conducted:

• ? Prevention of excessive pigmentation induced by UV exposure in Caucasian and Asian skins using a method that measures pigmentation protection factors (PPF).
• ? Efficacy against DNA damage by measurement of pyrimidine dimer formation and p53 protein accumulation.
• ? Protection of immune system using delayed type hypersensitivity (DTH) reactions to recall antigens, isomerization of urocanic acid (UCA), alteration of Langerhans cells (LC) density, morphology and function.
• ? Reduction of epidermal and dermal alterations induced by repeated UVA or UV solar simulated radiation (SSR) using histology or immunohistology.
• ? Prevention of the polymorphous light eruption (PMLE) in patients prone to develop this disease.

Results: Mexoryl^® SX‐containing formulations showed a dose‐dependent level of protection against pigmentation. For a same sun protection factor (SPF) the higher the UVA protection was, the higher was the PPF. Pyrimidine dimer formation and p53 accumulation were significantly reduced by formulations with Mexoryl^® SX. In the studies looking at the suppression of DTH reactions to recall antigens by the different UV spectra, the LC alterations and the cis UCA formation, Mexoryl^® SX formulations always showed a higher protective potency than sunscreen without it even when the protection against erythema was similar (products with same SPF). Mexoryl^® SX formulations also prevented or significantly decreased to minimal, ferritin, tenascin and lysozyme expression induced by repeated UVA or SSR exposure. It also reduced the enhancement of collagenase 2 mRNA expression induced by SSR exposure. Finally PMLE study demonstrated that UVA protection was essential for the prevention of this photodermatose. Conclusion: Mexoryl^® SX formulated in sunscreens or daily use products have been shown to be an effective UV absorber, leading to an increased efficacy of these products against a large number of biological damage induced by UVA, SSR or sun exposure.     

Intercellular pathway through hyaluronic acid in UVB‐induced inflammation

Ultraviolet B (UVB) radiation induces inflammation in the skin specifically at the site of exposure. We unexpectedly found that UVB‐induced inflammation was not induced in gp91phox‐depleted mice. To test whether gp91phox is directly involved in UVB‐induced inflammation, neutrophil‐ and hyaluronic acid–depleted mice were also irradiated and examined for their response. Hyaluronic acid–depleted mice showed strongly inhibited UVB‐induced inflammation, but the neutrophil‐depleted mice did not exhibit any suppressed UVB‐induced inflammation. To elucidate the pathway by which UVB irradiation induced inflammation, we examined the expression of nucleotide‐binding domain, leucine‐rich‐containing family, pyrin domain‐containing‐3 (NLRP3) and caspase‐1 in the mouse skin. An increase in the expression of NLRP3 and caspase‐1 was seen following the UVB irradiation of C57BL mice; however, the UVB‐irradiated gp91phox‐knockout (gp91phox^?/?) mice did not have this increase in expression. Furthermore, the plasma IL‐1β level increased after the UVB irradiation in C57BL mice, but there was no change in the gp91phox^?/? mice. These results clearly indicate that nicotinamide adenine dinucleotide phosphate oxidase is activated by gp91phox, which is expressed on the surface in response to the increased expression of hyaluronic acid induced by UVB irradiation, and as result, the generation of reactive oxygen species (ROS) increases. This ROS activate NLRP3, and NLRP3 leads to the production of caspase‐1, which subsequently increases IL‐1β, thereby finally inducing inflammation. It is thought that this system may play an important role in the damage and ageing of skin, and further studies are necessary to confirm these finding.     

A randomized, double-blind, negatively controlled pilot study to determine whether the use of emollients or calcipotriol alters the sensitivity of the skin to ultraviolet radiation during phototherapy with narrowband ultraviolet B

Background There is contradictory evidence suggesting that emollients increase, decrease or have no effect on minimal erythema dose (MED) or minimal phototoxic dose values prior to phototherapy. Few studies have looked at the in vivo use of emollients or calcipotriol prior to narrowband ultraviolet (UV) B (NB‐UVB) treatment. Objectives To investigate whether emollients or calcipotriol alter MED readings of skin on the back of healthy subjects prior to NB‐UVB irradiation. Methods Topical agents were applied to the backs of 20 healthy volunteers for 30 min prior to MED testing. These agents were aqueous cream, 50 : 50 white soft paraffin and liquid paraffin, Diprobase^® (Schering‐Plough, Welwyn Garden City, U.K.), Epaderm^® (Medlock, Oldham, U.K.) and calcipotriol ointment and cream. A control MED strip was used with no topical agent applied prior to testing. MED readings were recoded as integer steps between 1 and 9 (one is lowest MED dose for skin type; eight is highest; nine is no response, i.e. a higher MED). Results The median MED was between step 5 and 6 for all treatments and control. There was no significant difference at the 5% level between control and each topical agent. The study was powered to detect a median difference of approximately 0·4–0·6 steps. Conclusions This has important implications at a practical level when advising patients not to apply creams prior to treatment with NB‐UVB. Studies where agents are applied immediately prior to phototherapy have been more likely to show that emollients block transmission of UV radiation. If they are applied at least 30 min prior to treatment, they have no effect.     

Z‐ligustilide ameliorated ultraviolet B‐induced oxidative stress and inflammatory cytokine production in human keratinocytes through upregulation of Nrf2/HO‐1 and suppression of NF‐κB pathway

Ultraviolet B (UVB), a harmful environmental factor, is responsible for a variety of skin disorders including skin inflammation through reactive oxygen species (ROS) and inflammatory mediator production. Here, we investigated the effect of Z‐ligustilide (Z‐lig), an active ingredient isolated from the medicinal plants Cnidium officinale and Angelica acutiloba, on UVB‐induced ROS generation and inflammatory mediator production in normal human epidermal keratinocytes (NHEKs) as well as its underlying mechanisms. Z‐lig significantly rescued UVB‐induced NHEKs damage in a dosage‐dependent manner. Pretreatment of NHEKs with Z‐lig inhibited UVB‐induced ROS production in NHEKs. Both silencing the nuclear factor E2‐related factor 2 (Nrf2) and the supplement of tin protoporphyrin IX (SnPP), a haeme oxygenase‐1 (HO‐1) inhibitor, cancelled the inhibitory effect of Z‐lig on UVB‐induced ROS upregulation in NHEKs. Moreover, pretreatment of NHEKs with Z‐lig reduced UVB‐induced nuclear factor kappa B (NF‐κB)‐dependent inflammatory mediators (IL‐6, IL‐8 and MCP‐1) production at both mRNA and protein level. In the presence of Z‐lig, UVB‐induced NF‐κB subunit p65 nuclear translocation was abolished, and the IκBα degradation was suppressed. Taken together, these findings suggest that Z‐lig can suppress UVB‐induced ROS generation through Nrf2/HO‐1 upregulation and inflammation by suppressing the NF‐κB pathway, suggesting that Z‐lig may be beneficial in protecting skin from UVB exposure.     

A diffuse reflectance spectroscopic study of UV‐induced erythematous reaction across well‐defined borders in human skin

Introduction: The colour of tissue is often of clinical use in the diagnosis of tissue homeostasis and physiological responses to various stimuli. Determining tissue colour changes and borders, however, often poses an intricate problem and visual examination, constituting clinical praxis, does not allow them to be objectively characterized or quantified. Demands for increased inter‐ and intra‐observer reproducibility have been incentives for the introduction of objective methods and techniques for tissue colour (e.g. erythema) evaluation. The aim of the present paper was to study the border zone of a UVB‐provoked erythematous response of human skin in terms of blood volume and oxygenation measured by means of diffuse reflectance spectroscopy using a commercial probe. Material and methods: A provocation model, based on partial masking of irradiated skin areas, defines two erythema edges at every skin site responding to the UV irradiation. In every subject, five test sites were exposed with a constant UV light irradiance (14 mW/cm²), but with different exposure times (0, 3, 6, 9 and 12 s). An analysis of the spectral data measured across the two edges was performed for every scan line. The oxygenized and deoxygenized haemoglobin contents were estimated in every measurement point, using a modified Beer–Lambert model. Results: The fit of the experimental data to the model derived by the modified Beer–Lambert law was excellent (R²>0.95). Analysing data for the chromophore content showed that the erythematous response in the provoked areas is dominated by the increase in oxyhaemoglobin. The widths for the left and right border zone were estimated to be 1.81±0.93 and 1.90±0.88 mm, respectively (mean±SD). The unprovoked area between the two edges was estimated to be 0.77±0.68 mm. Conclusion: While the chosen data analysis performed satisfactorily, the ability of the probe design to differentiate the spatial aspects of a reaction with abrupt borders was found to be suboptimal resulting in a probable overestimation of the erythematous edge slope. Probe modification or imaging techniques are possible solutions.     

Ultraviolet B‐induced apoptosis of human skin fibroblasts involves activation of caspase‐8 and ‐3 with increased expression of vimentin

Background: After irradiation with a high dose of ultraviolet B (UVB), cells undergo apoptosis. Caspase‐8 and ‐3 are key mediators of apoptosis in many cells. Vimentin, an important cytoskeleton component, can be cleaved by caspase‐3, ‐6, ‐7 and ‐8. Cell apoptosis is promoted via caspase‐triggered proteolysis of vimentin. In this study, we explored the roles of caspase‐8 and ‐3 and the changes in vimentin expression in UVB‐induced apoptosis of human dermal fibroblasts. Methods: Skin fibroblasts were irradiated with 150 mJ/cm² UVB and cell death was monitored by the 3‐(4,5)‐dimethylthiahiazo(‐z‐y1)‐3,5‐diphenytetrazoliumromide assay and Hoechst staining. Caspase‐8 and ‐3 activities were detected by the caspase activity assay. Vimentin expression was assessed by immunofluorescence and Western blot. Results: Caspase‐8 and ‐3 were activated by 150 mJ/cm² UVB irradiation. Caspase‐8 and ‐3 activities changed in a time‐dependent way after UVB irradiation to induce apoptosis of fibroblasts, and caspase‐8 and ‐3 interacted with each other in this process. However, their substrate, vimentin, showed an enhanced expression over time after UVB irradiation. Conclusions: UVB‐triggered apoptosis of fibroblasts was dependent on the activation of caspase‐8 and ‐3 with an increased expression of vimentin.     

Effects of lotioned disposable handkerchiefs on skin barrier recovery after tape stripping

Background/purpose: In the present work, it was studied whether repeated use of lotioned disposable handkerchiefs on tape‐stripped forearm skin was able to improve skin barrier recovery. Methods: Skin assessments included scoring of visual erythema and dryness/scaliness; and measuring of skin redness (Chromameter^® CR300), skin hydration (Corneometer^® CM825), and transepidermal water loss (Tewameter^® TM300). Four different lotioned paper handkerchiefs – randomly assigned to one of two subject groups (n=20) – were tested vs. the non‐lotioned control handkerchief. The results were also compared with those obtained using a topically applied oil‐in‐water barrier cream (Dermalex^®). Results: The three‐day lasting protocol revealed that handkerchief wiping itself delayed skin recovery, but a significantly better performance was seen for the lotioned handkerchiefs containing fatty alcohols and mineral oils. This shows that the use of lotioned tissues helps to prevent skin damage inevitably caused by the wiping process. Conclusion: The controlled pre‐damaged forearm method with tape stripping appears to be a suitable model to study the effects of repetitive wiping on irritated skin with disposable handkerchiefs of different quality. More specifically, the model seems applicable to mimic the nasolabial skin damage observed during a common cold associated with frequent use of disposable handkerchiefs.     

Topical ceramides neither enhance UVB‐induced apoptosis in normal human keratinocytes nor affect viability in UVB‐irradiated reconstructed human epidermis

Ceramides are the major lipid of lamellar sheets present in intercellular spaces of the stratum corneum contributing to epidermal barrier properties. Therefore, ceramides and their analogues have been studied for barrier enhancing and water‐holding properties for decades. In vitro studies have indicated cytotoxic potential for cell‐permeable ceramides thereby raising the question whether topical ceramide application might contribute to UVB‐induced apoptosis. Phytosphingosine, N‐hexanoyl‐phytosphingosine and N‐stearoylphytosphingosine (ceramide III) in concentrations ≤5 μm have been used for co‐stimulation with low (160 J/m²) or high (600 J/m²) UVB doses in subconfluent basal and confluent differentiating keratinocytes. Significantly, increased caspase‐3 activity was observed in basal keratinocytes irradiated with 600 J/m² UVB and in differentiating keratinocytes with both UVB doses. Co‐stimulation with the named ceramides did not further increase (i) caspase‐3 activity and (ii) nucleosomal fragmentation in differentiating keratinocytes. Moreover, co‐stimulation with 1‐mm ceramides did not further affect viability/lactate dehydrogenase release in UVB‐irradiated reconstructed human epidermis corroborating the safety of these ceramides.     

NB‐UVB irradiation attenuates inflammatory response in psoriasis

Psoriasis is a chronic inflammatory disease characterized by immunological imbalance and vasodilation. Many triggering factors for psoriasis initiate inflammation via the activation of NF‐κB. Narrow‐band ultraviolet B (NB‐UVB) irradiation can be used as a general treatment for psoriasis, although the molecular mechanism has not yet been determined. The aim of this study was to elucidate the potential molecular mechanism of NB‐UVB irradiation therapy on psoriasis. We collected serum samples from patients with psoriasis and healthy control, and detected the expression of inflammatory factors by ELISA. In addition, we established mouse model of psoriasis. After different doses of NB‐UVB irradiation, the proportion of CD4⁺, CD8⁺, and CD11c⁺ cells in mouse spleen was detected by flow cytometry. Meanwhile, the expression of inflammatory factors in the damaged skin of mice was detected by RT‐PCR and Western blot analysis, and mouse serum levels of inflammatory factors were detected by ELISA. Our results showed that NB‐UVB irradiation regulated the expression of inflammatory factors in psoriasis patients. In mice, high‐dose NB‐UVB irradiation effectively eliminated IMQ‐induced psoriasis‐like dermatitis and inhibited the expression of pro‐inflammatory factors. In conclusion, our results indicate that NB‐UVB irradiation could regulate the expression of inflammatory factors and attenuate psoriasis plaques.     

Intralesional therapy of metastatic spreading melanoma with beta‐interferon

A 74‐year‐old female patient developed multiple local metastases after excision of a nodular melanoma of the left cheek. There was no regression after treatment with dacarbazine (DTIC^®) and radiotherapy. After treatment with intralesional interferon‐β, the metastases regressed completely. The dosage was 5 million IU interferon‐β (Fiblaferon^®) three times weekly with courses of two and four weeks, separated by a month. Except for local swelling and inflammation, no side effects occurred. Five years after completing therapy, the patient is still tumor‐free.     

Topical sodium cromoglicate relieves allergen‐ and histamine‐induced dermal pruritus

Background Sodium cromoglicate (SCG) has long been used in the management of allergic diseases, including as an ointment for atopic dermatitis. Although mast cell stabilization was initially considered as its mechanism of action, anti‐inflammatory actions and modulation of sensory nerve function have also been suggested. Objectives To investigate the mechanism(s) by which SCG relieves allergen‐ and histamine‐induced dermal inflammation by assessing its effects on pruritus, flare, skin temperature and weal volume. Methods Aqueous cream containing 0·2%, 1% or 4% SCG or no SCG (placebo) was applied in a randomized single‐blind manner to four areas on each forearm (two sites per arm) and covered with an occlusive dressing. One hour later, skin‐prick tests were performed in 20 allergic subjects with allergens to which they had previously shown sensitization, and in 40 nonallergic subjects with codeine (9 mg mL^?1, 20 subjects) and histamine (10 mg mL^?1, 20 subjects). Weal volume, skin temperature increase, erythema area and pruritus intensity were assessed at 0, 5, 10 and 15 min. Results SCG significantly (P < 0·05 to P < 0·001) reduced pruritus induced by all stimuli, with 4% SCG being most effective. Significant (P < 0·05 to P < 0·01) reductions of erythema area were also seen but there was no inhibition of weal volume or temperature increase. Conclusions SCG is effective in reducing pruritus but has no effect on weals, supporting the proposition that, in the skin, SCG inhibits sensory C‐fibre nerve activation rather than preventing mast cell degranulation. We suggest that topical SCG treatment, delivered in an appropriate vehicle, may be beneficial for symptomatic relief of pruritus in patients with cutaneous mastocytosis and other pruritic dermatoses.