A new in vitro method to predict in vivo photoprotection of skin hyperpigmentation induced by visible light.

BACKGROUND: Ultraviolet radiation is the main cause of skin pigmentation, but more recently visible light has been shown to be an important contributor especially in melano-competent subjects. Photoprotection from visible light can improve several hyperpigmentation disorders. Recently, a visible light photoprotection assessment method has been proposed based on in vivo pigmentation; the visible light photoprotection factor (VL-PF) is determined by assessment of the change in colorimetry parameter ITA over several days measured using a chromameter. Although in vivo methods remain the most representative of real life, in vitro methods are more suited to screening sunscreen formulations. OBJECTIVE: The aim of this study was to evaluate the correlation between in vivo and in vitro methods in assessing protection against visible light induced pigmentation. METHODS: We first analysed the in vitro protective properties of the 10 commercially available sunscreens using transmission measurements in the visible spectrum. Then, we performed a monocentric, double-blind, randomized controlled study with intra-individual comparisons in 20 healthy subjects and measure the VL-PF in vivo of those sunscreens. The correlation between the VL-PF and the percentage of blocked light was evaluated using the coefficient of determination R2 . RESULTS: A strong significant correlation was demonstrated between in vivo visible light protection factor and in vitro transmittance measurements, with the highest correlation factor at 420 nm and in the spectrum covering from 400 to 469 nm. CONCLUSION: Transmittance measurements were found to be a good predictive tool to evaluate sunscreen visible light photoprotection efficacy and could be used to select formulations for final in vivo testing.

Vasoconstrictor potency of fixed-dose combination calcipotriol (50 µg/g) and betamethasone dipropionate (0.5 mg/g) cutaneous foam versus other topical corticosteroids used to treat psoriasis vulgaris.

Background: It is important to determine the vasoconstrictor potencies of topical corticosteroids used to treat psoriasis to ensure appropriate clinical use. Objective: To compare the vasoconstrictive potencies of fixed-dose combination calcipotriol (50 µg/g) and betamethasone dipropionate (0.5 mg/g) (Cal/BD) cutaneous foam with other topical corticosteroids. Methods: In this Phase I, single-center, healthy volunteer study, Cal/BD foam, clobetasol propionate 0.05% cream (CP; very potent), BD 0.05% ointment (potent), mometasone furoate 0.1% cream (MF; potent), hydrocortisone-17-butyrate 0.1% ointment (HB; moderately potent), and foam vehicle were applied, then removed after 16 h. Skin blanching was visually assessed 2 h later (scale of 0-4). Results: Thirty-six volunteers were randomized. Skin blanching with Cal/BD foam (median [range], 2.00 [0.75-3.00]) was significantly lower than CP cream (3.00 [1.75-4.00]; p < .001), was not significantly different from BD ointment (1.75 [0.75-3.00]; p = .30) and MF cream (2.00 [1.00-3.75]; p = .22), and was significantly greater than HB ointment (1.25 [0.50-3.00]; p < .001) and vehicle (0 [0-0.50]; p < .001). There were no local tolerability reactions or adverse events. Conclusions: The corticosteroid potency of Cal/BD foam was not significantly different from BD ointment and MF cream, significantly stronger than HB ointment, but weaker than CP cream in healthy volunteers.

Noninvasive proteome analysis of psoriatic stratum corneum reflects pathophysiological pathways and is useful for drug profiling.

BACKGROUND: Protein expression is disturbed in the psoriatic stratum corneum (SC). Noninvasive methods for the description of pathophysiological changes and drug profiling in psoriasis are desirable. OBJECTIVES: Undertake large-scale noninvasive protein expression studies in psoriatic SC to identify biomarkers of pathophysiological processes and use them for drug profiling. METHODS: Psoriatic SC was harvested through repetitive tape-stripping. Nonlesional and lesional SC, as well as vehicle-treated and drug-treated lesional SC samples were collected. Protein extracts from nonlesional and lesional skin biopsies were used for comparison. Calcipotriol-betamethasone (CB) was used as a reference medication. Proteins extracted from pooled tape strips were quantified using mass spectrometry (MS), Western blotting, enzyme-linked immunosorbent assay and Luminex technologies. RESULTS: MS-based methods identified 140 proteins differentially expressed in psoriatic SC. Epidermis development, glycolysis, regulation of apoptosis, cytoskeleton organization and peptide cross-linking were modulated, all reflecting perturbed epidermal differentiation. Using antibody-based techniques, increased levels of sICAM1, of CXCL1- and CXCL8-attracting neutrophils, of CXCL10- and CCL4-attracting T helper (Th) 1 cells, and of CCL2- and CCL4-attracting monocytes and dendritic cells were observed. Quantification of the Th1 and Th17 markers tumour necrosis factor, interleukin (IL) 12B, IL17A and IL17F in lesional SC was successful, while the Th2 cytokines IL4, IL5 and IL13, not involved in the disease process, were not detected. The pruritic cytokine IL31 was detected in lesional SC. CXCL1, CXCL8, CXCL10 and sICAM were used to investigate disease remission, ranking three topical treatments according to their known clinical efficacy. CONCLUSIONS: Protein biomarker quantification in psoriatic SC detects key pathophysiological mechanisms and enables noninvasive drug profiling in translational medicine settings.

Enhanced vasoconstrictor potency of the fixed combination calcipotriol plus betamethasone dipropionate in an innovative aerosol foam formulation vs. other corticosteroid psoriasis treatments.

BACKGROUND: An aerosol foam formulation of fixed combination calcipotriol 50 µg/g (Cal) and betamethasone 0.5 mg/g (as dipropionate; BD) has been developed for psoriasis vulgaris treatment. OBJECTIVE: To compare Cal/BD aerosol foam pharmacodynamic activity with Cal/BD ointment and with other topical corticosteroids of different potencies by assessing vasoconstrictor potential. METHODS: A Phase I, single-centre, investigator-blinded, vehicle-controlled, intra-individual comparison vasoconstriction study. Healthy volunteers received a single application on selected sites of: Cal/BD aerosol foam, clobetasol propionate 0.5 mg/g cream (CP; very potent), Cal/BD ointment (potent), fluocinolone acetonide 0.25 mg/g ointment (FA; moderately potent), BD aerosol foam and aerosol foam vehicle. A seventh untreated site acted as a negative control. Skin blanching was assessed by visual (primary response criterion) and colorimetric a* and L* measurements (secondary criteria), and was analysed over time (6-32 h post-application). RESULTS: Thirty-five healthy volunteers were included. All active treatments led to significantly greater skin blanching than control. By visual assessment, skin blanching with Cal/BD aerosol foam was significantly less compared with CP cream [mean AUC0-32 2560 vs. 3831; mean difference = -1272; 95% confidence interval (CI): -1598, -945; P < 0.001], similar to BD aerosol foam (mean AUC0-32 2560 vs. 2595; mean difference = -35; 95% CI: -362, 292; P = 0.83) and significantly greater than Cal/BD ointment (mean AUC0-32 2560 vs. 2008; mean difference = 552; 95% CI: 225, 878; P = 0.001) and FA ointment (mean AUC0-32 2560 vs. 1981; mean difference = 578; 95% CI: 251, 905; P < 0.001). Colorimetric assessments a* and L* also indicated significantly reduced skin blanching with Cal/BD aerosol foam compared with CP cream. No adverse events (AEs) were reported. CONCLUSION: Cal/BD aerosol foam can be considered a more potent formulation than Cal/BD ointment and the moderately potent FA ointment, but less potent than the very potent corticosteroid, CP cream.

Clinical evidence of benefits of a dietary supplement containing probiotic and carotenoids on ultraviolet-induced skin damage.

BACKGROUND: Lactobacillus johnsonii (La1) has been reported to protect skin immune system homeostasis following ultraviolet (UV) exposure. OBJECTIVES: To assess the effects of a dietary supplement (DS) combining La1 and nutritional doses of carotenoids on early UV-induced skin damage. METHODS: Three clinical trials (CT1, CT2, CT3) were performed using different UV sources: nonextreme UV with a high UVA irradiance (UV-DL, CT1), extreme simulated solar radiation (UV-SSR, CT2) and natural sunlight (CT3). All three clinical trials were carried out in healthy women over 18 years of age with skin type II-IV. In CT1, early markers of UV-induced skin damage were assessed using histology and immunohistochemistry. In CT2, the minimal erythemal dose (MED) was determined by clinical evaluation and by chromametry. Chromametry was also used to evaluate skin colour. Dermatologists' and subjects' assessments were compiled in CT3. RESULTS: A 10-week DS intake prevented the UV-DL-induced decrease in Langerhans cell density and the increase in factor XIIIa+ type I dermal dendrocytes while it reduced dermal inflammatory cells. Clinical and instrumental MED rose by 20% and 19%, respectively, and skin colour was intensified, as shown by the increase in the ΔE* parameter. The efficacy of DS was confirmed by dermatologists and subjects under real conditions of use. CONCLUSIONS: Nutritional supplementation combining a specific probiotic (La1) and nutritional doses of carotenoids reduced early UV-induced skin damage caused by simulated or natural sun exposure in a large panel of subjects (n=139). This latter result might suggest that DS intake could have a beneficial influence on the long-term effects of UV exposure and more specifically on skin photoageing.

Cellulite and skin ageing: is there any interaction?

OBJECTIVE: This study aimed to identify the characteristics of cellulite in women of different age and to appreciate whether cellulite could interfere with skin ageing or not. METHODS: 94 Healthy females, divided into three age groups (21-30yrs; 31-40yrs; 51-60yrs) and two grade groups of cellulite (grade 2; grade 0 or control group), were investigated using non invasive techniques. The "orange peel appearance" was quantified by measuring the shadowed surfaces under low angle light. The biomechanichal properties were measured (extensibility-retractability-elasticity). The thicknesses of the skin structures were also evaluated using ultrasound. Echogenicity of the dermis was recorded and dermis density determined in two bands (superficial and low dermis). RESULTS: In grade 2, the shadowed surfaces are significantly different according to age; i.e. smaller and more numerous after age of 30; the total skin thickness including hypodermis is increased of about 30% irrespective to age, compared to control group. The biomechanical properties of the skin are significantly modified as age increases without any grade effect. In grade 2, retractability and elasticity parameters are altered from age 30 whilst only from age 50 in the control group. Echogenicities of the superficial and deep dermis also decrease from age 30 and become significantly lower than the ones of grade 0. CONCLUSION: Population with cellulite presents earlier skin ageing characteristics than the control population. Two sub-populations may exist: the under 30 age with large dimpled surfaces, normal biomechanical and density properties; and the over 30 age with smaller and numerous dimpled surfaces and already altered dermis properties. This premature skin ageing should be prevented accordingly.

Evaluation of the effect of Dardia Lipo Line on skin inflammation induced by surfactants using the repeated open-application test.

BACKGROUND: Medical skin care products are topical preparations with mainly moisturizing properties. A new line of medical skin products with an excellent tolerability profile and improved hydration for dry skin has been developed, but beneficial effects have not yet been investigated on damaged skin. AIM: To investigate if these products maintain barrier function and hydration status, improve subjective symptoms due to irritant contact dermatitis and to prove their tolerability on damaged skin. DESIGN AND METHODS: Single-centre, blinded, randomized, controlled study in 20 healthy Caucasian women. 5% sodium lauryl sulphate solution was used to induce skin irritation. Two sites on the inside surface of both forearms of each subject were treated daily for 5 days (irritation period). Lipo Cream, Lipo Milk (water-in-oil emulsions) and Lipo Ointment (water-free formulation) were applied twice daily to three of the four test sites on days 1-5. The fourth site was used as a control. Visual readings, subjective symptom assessments, transepidermal water loss (TEWL) and colorimetric measurements, corneometry and skin microrelief macrophotographies were done on days 1-6. RESULTS: On day 6, TEWL was increased vs baseline on all sites; however, TEWL with Lipo Cream or Lipo Ointment was significantly lower than control. At day 6, skin capacitance was 94%, 100% and 85% of baseline value for the cream, milk and ointment, respectively, versus 72% for control. All test products were well tolerated. CONCLUSIONS: Lipo Line products showed both protective properties against epidermal dysfunction and significant hydrating effect.

Stratum corneum pharmacokinetics of the anti-fungal drug, terbinafine, in a novel topical formulation, for single-dose application in dermatophytoses.

OBJECTIVE: The stratum corneum (SC) pharmacokinetics of terbinafine following single-dose administration of a novel cutaneous solution (film-forming solution, FFS) containing terbinafine hydrochloride and a film-forming agent, was investigated in three studies. Terbinafine 1% cream (Lamisil) was included as a benchmark in two of these studies. RESEARCH DESIGN AND METHODS: Drugs were applied to areas of the back, and skin strips were taken from defined areas at baseline and from 1 to 312 h after application. Samples were analysed using validated liquid chromatography/mass spectrometry. RESULTS: The residence time of the film on the skin was up to 72 h after application (up to 12 h for the 1% cream). After application of terbinafine FFS, 30% of the total amount of drug delivered into the SC occurred during the first 2 h, 31% from 2-12 h, and 39% thereafter. The C(max) was observed as early as 1.5 h (t(max)). SC levels were still detected after 13 days (24 ng/cm(2)) (t(1/2)) was 162 h). Terbinafine 1% cream showed a similar t(max) (2 h) with a lower C(max) than terbinafine 1% FFS, and mean SC levels after 7 days of treatment were 46 ng/cm(2) (day 13). The t(1/2) was 68 h. Washing at 30 min removed 86% of the film still present on the surface; the decrease of terbinafine concentration in the SC was 84%. A later washing at 12 h removed 73% of the film in comparison to non-washed skin and induced a decrease in the terbinafine content in the SC of 27%. CONCLUSIONS: The SC pharmacokinetic profile of terbinafine 1% FFS indicates that this novel formulation is efficient in delivering high amounts of terbinafine to the skin for a prolonged time and supports its use in the treatment of dermatophytoses with a single application.

Evaluation of efficacy and safety of rucinol serum in patients with melasma: a randomized controlled trial.

BACKGROUND: Melasma is a hyperpigmentation disorder predominantly affecting sun-exposed areas in women, which is often refractory to treatment. Most commercially available treatments incorporate inhibitors of tyrosinase, a key enzyme in melanin production within the melanocyte. In general, however, the efficacy of these therapies is somewhat limited. Recent studies have identified other enzymes that play an important role in melanogenesis, including tyrosinase-related protein-1 (TRP-1), which catalyses the oxidation of the melanogenetic intermediate 5,6-dihydroxyindole-2-carbolylic acid. Rucinol (4-n-butylresorcinol) has been shown to inhibit the activity of both tyrosinase and TRP-1. OBJECTIVES: To assess the efficacy of rucinol serum 0.3% vs. the corresponding vehicle as a treatment for melasma. Secondary objectives were to evaluate local and general tolerability and to assess the skin acceptability of rucinol serum in the target population. METHODS: In this prospective, single-centre, double-blind, randomized, vehicle-controlled, bilateral (split-face) comparative trial, 32 women with melasma were provided with two identical tubes containing rucinol serum 0.3% or vehicle. The products were each applied to one-half of the face, according to the randomization scheme, twice daily for 12 weeks (phase 1). A broad-spectrum sunscreen (sun protection factor 60) was also applied daily. Assessments at baseline, 4, 8 and 12 weeks included clinical evaluations by a dermatologist, chromametry, ultraviolet and standard photography, and assessments of skin acceptability and tolerability. After 12 weeks, patients were given the option of an additional 3-month treatment period of open full-face rucinol treatment, with reviews at 16, 20 and 24 weeks (phase 2). RESULTS: Twenty-eight patients completed phase 1 and 26 patients completed phase 2. After 12 weeks, the clinical pigmentation score for rucinol-treated skin was significantly lower than for vehicle-treated skin (P = 0.027). During phase 2, rucinol induced a significant reduction in mean pigmentation score on the half of the face previously treated with vehicle. There was also a further, significant improvement on the rucinol-treated side of the face. Chromametry measurements showed that skin was significantly lighter and less yellow, with a strong trend towards reduced redness, following rucinol therapy compared with vehicle. Rucinol serum showed good tolerability and acceptability and was considered to have good or fair efficacy by 78% of the patient population. CONCLUSIONS: Rucinol serum was shown to have significant efficacy compared with vehicle alone in improving melasma after 3 months of treatment, according to clinical and objective assessments of skin colour.

[Assessment of the photosensitization potential of zinc gluconate]. / Evaluation du potentiel photosensibilisant du gluconate de zinc.

INTRODUCTION: Tolerance and clinical efficacy of zinc gluconate are well documented, however, no study have evaluated its photosensitizing potential. It is well known that many treatments of acne are photosensitizing. Evaluation of the photosensitizing potential of zinc gluconate was the aim of this study. PATIENTS AND METHOD: Two open, monocentric studies were carried out with acneic volunteers. The methodology used in this study was an adaptation from that existing for the evaluation of the photosensitizing potential of topical products. In the study of phototoxic potential, volunteers were exposed to 20 J/cm2 UVA and to 0.75 times MED, before and after administration of zinc gluconate. Clinical and colorimetric evaluations of reactions were then carried out 1, 24, 48 and 72 hrs after exposure. In the photoallergic potential study, during the first week of the induction phase, the volunteers were exposed to 2 times MED, and to 3 times the MED during the second and third week. Then during the challenge phase, they were exposed t o4 J/cm2 UVA and to 0.75 times MED. Zinc gluconate was administered throughout the study. Clinical and colorimetric evaluations of reactions were carried out 24, 48 and 72 hrs after exposure, only during the challenge phase. RESULTS: The majority of clinical scores measured on scales at 6 and 5 levels were equal to 0 and 0.5 (evaluation of the phototoxic potential) or all equal to 0 (evaluation of the photoallergic potential). Thus zinc gluconate did not induce phototoxic or photosensitive reactions, whatever the ultraviolet type used. DISCUSSION: Since zinc gluconate does not induce any photosensitive reaction, it could be prescribed during periods of exposure to sun.

Diclofenac-Na gel is effective in reducing the pain and inflammation associated with exposure to ultraviolet light - results of two clinical studies.

The potential of a diclofenac-Na Emulgel (diclofenac gel) to alleviate the pain and associated symptoms caused by sunburn has been evaluated versus vehicle. Sunburn was induced on the buttock skin of healthy adult male subjects by irradiation with UVA + UVB rays. Investigational products were applied 6 and 10 h after irradiation, and efficacy was assessed on the basis of spontaneous and provoked pain, erythema, oedema, skin colour and temperature. The minimal efficacious concentration evaluated in an extension (0.1 vs. 0.25% diclofenac gel) of a previous concentration-finding study (1, 0.5 and 0.25% diclofenac gel) was 0.1% and was efficacious in alleviating pain (spontaneous and provoked) as well as reducing erythema, oedema and skin temperature. In a single- versus 2-application comparison study, a single application of 0.1% gel was sufficient to alleviate the pain and accompanying symptoms of sunburn with an onset of action 2 h after application. A second application of gel 4 h after the first maintained the analgesia and reduction of other symptoms for a period of up to 48 h after irradiation.

A randomized, controlled study of the safety and efficacy of topical corticosteroid treatments of sunburn in healthy volunteers.

Topical glucocorticosteroids are frequently used for the treatment of sunburn despite the scarcity of randomized, double-blind controlled trials to support this indication. This randomized, intra-individually controlled trial compared the efficacy and safety of two topical glucocorticosteroids, 0.1% methylprednisolone aceponate milk (MPA) and 0.1% hydrocortisone 17-butyrate emulsion (HCB), for treatment of sunburn in 24 healthy volunteers of skin type III. After irradiation of the skin by simulated sunlight, treatments were blinded and randomly allocated to 36 cm2 test areas on both sides of the spine. Volunteers were treated twice daily for 7 days and assessed daily with 1-day follow-up. The untreated area was not blinded. Primary efficacy measures were sum score and sunburn reaction based on erythema, oedema, burning and itching. Secondary efficacy measures were physician's global assessment, individual signs/symptoms, colorimetry, dermatological improvement, and time to healing. Intra-individual comparisons were made. Differences in sum score were apparent on days 3-4 and significant on days 4-5 for corticosteroids compared with nontreatment. Treated areas had significantly lower sunburn reaction than untreated areas (P = 0.1% and P = 0.5% for MPA and HCB, respectively). Differences between treatments were not significant. Secondary efficacy measures were in line with these findings. None of the three adverse events reported were considered to be related to treatment. We conclude that MPA and HCB are safe and effective in the treatment of sunburn.