Nuclear and Urinary Measurements Show the Efficacy of Sun-Protection Factor 50+ Sunscreen against DNA Photoproducts upon Real-Life Recreational Exposure.

Sunscreens have been shown to protect against UVR-induced DNA damage in human skin under laboratory conditions. We presently extended these observations to real-life conditions in volunteers after their ordinary exposure habits during summer holidays. Volunteers were randomly assigned to a control group and an educated group supplied with a SPF ≥50 sunscreen and receiving instructions for use. A questionnaire was used to determine the extent of exposure. No difference in average solar UVR exposure was found between the two groups. DNA photoprotection was first assessed by, to our knowledge, a previously unreported noninvasive assay on the basis of the quantification of pyrimidine dimers released by DNA repair in urine. Damage was also quantified in the nuclear DNA extracted from the roof of suction blisters collected after recreational exposure. The urinary concentration of photoproducts was significantly higher in the control than in the educated group. The same trend was observed for the level of photoproducts in the DNA from suction blisters. The unambiguous observation of an efficient photoprotection against DNA damage afforded by sunscreen under real-life conditions provides strong support for the efficiency of the sunscreens. In addition, the results validate the use of urinary DNA photoproducts as a noninvasive assay applicable to photoprotection.

Efficacy of Avène Hydrotherapy on Chronic Pruritus in Patients with Plaque Psoriasis.

INTRODUCTION: Pruritus is a prevalent symptom, described as one of the most bothersome of psoriasis. Specific itch management remains a challenge, for which hydrotherapy could be used as adjunct care to medical treatment. Therefore, we assessed the immediate and longer-term benefit of 3 weeks of Avène thermal spring water hydrotherapy on chronic pruritus in patients in addition to their usual psoriasis and/or pruritus management. METHODS: Twenty-six patients suffering from chronic pruritus due to psoriasis were evaluated before and after 3 weeks of hydrotherapy with a 3 and 6 month follow-up. A control group (18 patients) did not undergo hydrotherapy and continued to follow their usual skin management. Pruritus was assessed according to the numeric rating scale (NRS, pruritus intensity), the visual dynamic pruritus score (vDPS, change in pruritus intensity), and the 5-D itch scale (pruritus characteristics). Psoriasis severity was measured using the psoriasis area and severity index (PASI) score. The "itchy quality of life" (ItchQoL) scale was used to assess quality-of-life (QoL) impact related to itch. Pruritus and psoriasis gene and protein biomarkers were measured in lesional and nonlesional skin. RESULTS: Pruritus measurements (NRS, vDPS, and 5-D itch scale) indicated an immediate and long-lasting positive effect of hydrotherapy compared with control patients. The psoriasis area and severity index (PASI) was decreased by 40.0% by hydrotherapy, which was sustained over 6 months. The ItchQoL also improved directly after hydrotherapy, which was still much improved even 6 months later. Analysis of gene and/or protein biomarkers revealed a significant decrease of inflammation biomarkers (IL-8, IL-1α, IL-1RA, and RANTES), of psoriasis biomarkers (PI3, S100A7, and IL-17), and of pruritus biomarkers (IL-31, TRPV1, and CGRP1). CONCLUSIONS: These findings demonstrated an immediate and long-lasting improvement of pruritus in patients with psoriasis who underwent Avène thermal spring water hydrotherapy, indicating that this would be a good complementary therapy in the management of this disease. TRIAL REGISTRATION: NCT03023254.

In vivo evaluation of sunscreen application by multispectral imaging: A new tool for educating sunscreen users.

BACKGROUND: The sun protection factor (SPF) of sunscreens is evaluated using standardized protocols based on the application of 2 mg/cm2 of product. However, the amount of product applied by sunscreen users in real life is likely to be much lower. OBJECTIVES: To evaluate a new multispectral imaging approach for determining the actual quantity of sunscreen applied by users and to assess the benefits of an application guide for the use of an SPF 50+ sunscreen. MATERIALS AND METHODS: Analyses of the reflectance spectra obtained from multispectral images were used to determine the actual dose of sunscreen that 26 healthy volunteers applied to their face following three application modalities: a single application, reapplication after 30 min, and application according to an instruction guide. RESULTS: Without the application guide, volunteers applied an average of 1.04 mg/cm2 of sunscreen during the single application and 1.23 mg/cm2 during the repeated application. With the application guide, the amount of sunscreen applied was 1.45 mg/cm2 : around 40% higher than during the single application. Spreading of the sunscreen was also less uniform with the unguided single application than with the other application modalities. CONCLUSIONS: This study showed that the multispectral imaging approach can be used to measure the amount of sunscreen applied in vivo. Our findings confirmed that the standard dose used for SPF measurements and other sunscreen tests is far higher than that applied by users in practice. Providing users with precise guidelines could increase the amount of sunscreen applied, resulting in more adequate photoprotection.

The usefulness of a dermocosmetic containing Myrtus communis extract and azelaic acid for maintenance phase of adult female acne: Results from a randomized exploratory investigator-blinded comparative study.

BACKGROUND: Acne is a very common condition. Currently, there are relatively few studies available to help guidance-based decisions for its long-term management, especially studies with cosmetic care products. We have developed a skin care product dedicated to adult female acne. OBJECTIVES: Evaluate the efficacy and tolerance of the test product containing Myrtus communis extract and azelaic acid compared with a light moisturizing cream (LCM) in adult females in the acne maintenance phase. METHODS: A clinical study was conducted as a Brazilian, multicentre, randomized, investigator-blinded trial in adult females with clear or almost clear facial acne after anti-acne treatment. The test group (26 subjects) applied the test product and the comparative product group (27 subjects) applied LCM. Both groups applied the products twice daily on the whole face. Subjects were evaluated every 4 weeks over 16 weeks. Efficacy was evaluated according to acne relapse; Investigator's Global Assessment (IGA); acne lesions counting; AcneQoL questionnaire; Subject Global change Assessment (SGA) of acne severity; and the number of Post-Inflammatory Hyperpigmentation (PIH) and Post-Inflammatory Erythema (PIE) lesions. Tolerance was assessed according to a 5-point scale. RESULTS: Over 16 weeks, the number of acne relapse was more than double in the comparator compared to the test product group (eight subjects vs. three subjects respectively). There was no statistical difference in the evolution of the mean IGA from baseline between the two groups; however, 85% of subjects were assessed as clear or almost clear in the test product group and 67% in the comparative group. CONCLUSIONS: This study demonstrated the effectiveness topical application of the test product compared to LCM on acne severity in the maintenance phase of adult female acne. Efficacy results after 16 weeks suggested a trend to limit acne relapses and a benefit of the test product in maintaining long-term remission.

Assessment of wound healing efficacy and tolerability using CicatrylTM cream based on a suction blister model in healthy subjects

Background: CicatrylTM cream, a topical medical device, is indicated for the treatment of superficial wounds and small skin injuries. Objectives: To assess the efficacy and tolerability of CicatrylTM cream by measuring the recovery of the skin barrier after inducing wounds. Materials & Methods: A suction blister of about 6-mm diameter was induced on the inner side of each forearm of 44 healthy subjects. Using a process of randomisation, CicatrylTM cream was then applied to one wound for a maximum duration of 14 days, while the other wound was left untreated. The primary objective was to evaluate the effect of the test product on wound healing at Day 6, by comparing treated versus untreated wound areas measured by macrophotography. Secondary objectives were to evaluate healing, cutaneous barrier restoration and subjective efficacy of the cream as well as tolerability. Results: The mean wound area (± SD) at Day 6 was significantly smaller for treated wounds compared with untreated wounds (1.76±4.71 vs 15.76±7.61 mm2; p < 0.0001). For treated wounds, wound healing between Days 1 and 6 was 1.6-fold faster compared with untreated wounds (-7.90 vs-4.79 mm2/day; p < 0.0001), and the wounds healed in approximately half the time (6.8 vs 12.2 days for untreated wounds). Cutaneous barrier restoration occurred earlier for treated wounds (Day 6 vs Day 8 for untreated wounds). The cream was well tolerated, and no serious adverse events were observed. Conclusion: CicatrylTM cream improves wound healing, especially within the first six days, if applied in accordance with the manufacturer's instructions.

Long-Term Use of Silybum marianum fruit extract Contributes to Homeostasis in Acne-Prone Skin-A 12-Month Follow-Up International "Real Life" Cohort Study.

BACKGROUND: Homeostasis in the differentiation programme of sebaceous stem cells has been identified as a key step in comedogenesis and should be a target for acne-prone skin care. OBJECTIVE: To report on a multicentre, year-long/real-life use study of a patented natural product containing S. marianum fruit extract proven to modulate molecular actors in the initial steps of comedogenesis. METHODS: An open-label multicentric international study, with a 12 month follow-up, included 54 teenage and young adult subjects with mild to moderate facial acne. The study was aimed at reproducing a real-life use context. RESULTS: Total lesion count mean was 88.3 at inclusion. There was a sustained, highly significant decrease over the months of clinical lesion counts (45.6% improvement after 6 months and 59.6% at 12 months) and on other efficacy markers, associated with a significant decrease in global microcomedone quantity on cyanoacrylate superficial skin surface biopsies. Importantly, the study protocol allowed the dermatologist to prescribe, if needed as in real life, any of the acne drugs registered in the acne guidelines. The exposure to these acne drugs during the whole year was calculated as a percentage of S. marianum fruit extract/352 days of use and happened to be very limited at less than 4%, which indicates a marginal contribution to the sustained clinical improvement. (Oral and local acne treatments: Lymecycline 1.46%; Doxycycline 0.24%; Adapalene 0.16% or gel association with Benzoyl peroxide 1.17%; Clindamycin 0.04%; Benzoyl peroxide 1.5%; Erythromycin 0.75%). The tolerance with daily S. marianum fruit extract long-term use was good. LIMITATIONS: The association with routine prescription acne drugs when needed, even if limited, does not allow a full evaluation of the intrinsic quantitative efficacy of S. marianum fruit extract in lesion reduction. CONCLUSION: This open, real-life, year-long multicentre study confirms a previous 48-week proof of concept study and qualifies the use of S. marianum fruit extract as a "field-dermo cosmetic" contributing to homeostasis of acne-prone skin in association with acne drugs.

Lipid Droplet Proteins in Acne Skin: A Sound Target for the Maintenance of Low Comedogenic Sebum and Acne-Prone Skin Health.

In adipocytes and sebocytes, lipid droplet proteins control the storage of lipids in organized droplets and their release on demand. The contribution of lipid droplet proteins to the pathogenesis of acne is plausible because they control the levels of comedogenic free fatty acids. The expression of two lipid droplet proteins, CIDEA and PLIN2, was analyzed in the skin of patients with acne by immunohistochemistry and western blotting. The design of clinical protocols allowed correlating the expression of CIDEA and PLIN2 with both comedogenesis and the release of free fatty acids. Both proteins were detected by immunohistochemistry in the sebaceous glands of patients with acne, with a disturbed expression pattern of PLIN2 compared with that in the controls. Higher levels of PLIN2 and CIDEA, as detected by western blotting in the infundibulum, significantly correlated with lower ongoing comedogenesis over 48 weeks of Silybum marianum fruit extract application. Accordingly, free fatty acid release from sebum triglycerides was significantly decreased, as shown with two distinct methods. The data are consistent with the expected role of PLIN2 and CIDEA in the prevention of comedogenic free fatty acid release. Modulation of PLIN2 and CIDEA expression appears as a sound target for the maintenance of low comedogenic sebum and acne-prone skin health.

Dermal fiber structures and photoaging.

The use of multiphoton imaging has become a standard technique to visualize the dermis fibers as it requires no specific staining. The density and organization of collagen and elastin are common markers of skin intrinsic aging and photoaging; thus, there is a need of grading this skin aging with quantitative indicators able to provide a robust evaluation of the dermis fibers' state. We propose a systematic analysis of multiphoton images of skin biopsies taken on the buttock and the forearm of patients of different ages. The intensity histograms of images were analyzed through their moments, a wavelet decomposition was done, and the wavelet coefficients distribution was fitted by a generalized Gaussian distribution. Different parameters relative to the collagen or elastin densities, organizations, and structures were calculated and exhibit phenomena specific to intrinsic or extrinsic aging. Those indicators could become a standard method to analyze the degree of skin aging (intrinsic or extrinsic) through multiphoton imaging.

Clinical and biochemical assessment of maintenance treatment in chronic recurrent seborrheic dermatitis: randomized controlled study.

INTRODUCTION: Few studies have investigated the long-term effects of a maintenance regimen in the prevention of relapses in scalp seborrheic dermatitis (SD), in particular following biomarker changes. MATERIALS AND METHODS: A new shampoo containing beta-glycyrrhetinic acid (18ßGA) in addition to cyclopiroxolamine (CPO) and zinc pyrithione (ZP) was tested in 67 subjects suffering from SD with moderate to severe erythema and itching in a biphasic study. After a first common intensive treatment phase (investigational product thrice a week × 2 weeks), subjects randomly received the investigational product once a week × 8 weeks (maintenance) or a neutral shampoo (discontinuation) in a comparative, parallel group maintenance phase. Efficacy was assessed clinically (overall clinical dandruff score, erythema, overall efficacy, self-evaluation), biochemically and microbiologically by quantitative polymerase chain reaction (qPCR), high performance liquid chromatography (HPLC) or enzyme-linked immunoabsorbent assay (ELISA) analysis of scale samples (Malassezia species (restricta and globosa), cohesion proteins (plakoglobins), inflammation (Interleukin (IL)-8, IL-1RA/IL-1α) and pruritus (histamine, cathepsin S) markers). RESULTS: During the intensive treatment phase, SD improved significantly (p < 0.0001) with a decrease in clinical signs as well as Malassezia species, cohesion proteins, inflammation and pruritus markers. During the maintenance phase, the improvement persisted in the 'maintenance' group only, with a significant intergroup difference. A consistently positive relationship was found between dandruff, itching, erythema and Malassezia populations, histamine levels and IL-1RA/IL-1α ratio. CONCLUSION: The effectiveness of this maintenance regimen was objectively demonstrated at the clinical, biochemical and microbiological level. Correlations between clinical signs and biomarkers could provide clues to explain the resolution of SD and confirm the interest of biomarkers for SD treatment assessment.

In vivo quantification of epidermis pigmentation and dermis papilla density with reflectance confocal microscopy: variations with age and skin phototype.

Reflectance confocal microscopy (RCM) may help to quantify variations of skin pigmentation induced by different stimuli such as UV radiation or therapeutic intervention. The objective of our work was to identify RCM parameters able to quantify in vivo dermis papilla density and epidermis pigmentation potentially applicable in clinical studies. The study included 111 healthy female volunteers with phototypes I-VI. Photo-exposed and photo-protected anatomical sites were imaged. The effect of age was also assessed. Four epidermis components were specifically investigated: stratum corneum, stratum spinosum, basal epidermal layer and dermo-epidermal junction. Laser power, diameter of corneocytes and upper spinous keratinocytes, brightness of upper spinous and interpapillary spinous keratinocytes, number of dermal papillae and papillary contrast were systematically assessed. Papillary contrast measured at the dermo-epidermal junction appeared to be a reliable marker of epidermis pigmentation and showed a strong correlation with skin pigmentation assessed clinically using the Fitzpatrick's classification. Brightness of upper spinous and interpapillary spinous keratinocytes was not influenced by the skin phototype. The number of dermal papillae was significantly lower in subjects with phototypes I-II as compared with darker skin subjects. A dramatic reduction in the number of dermal papillae was noticed with age, particularly in subjects with fair skin. The method presented here provides a new in vivo investigation tool for quantification of dermis papilla density and epidermal pigmentation. Papillary contrast measured at the dermo-epidermal junction may be selected as a marker of skin pigmentation for evaluation in clinical studies.

Adhesiveness of a new testosterone-in-adhesive matrix patch after extreme conditions.

The objective of the study was to evaluate the adhesiveness of a new thin, transparent and comfortable testosterone-in-adhesive matrix patch, Testopatch, after extreme conditions. The study was a single-centre, open-label with randomization of sites (upper arms, lower back, thighs) and sides (left, right) of two 45 cm(2) patches, in 24 healthy subjects. Patches were symmetrically applied on one of the three sites. One patch was removed after 2.0 h, under resting conditions and the other patch was removed at 3.5 h, after extreme conditions (physical exercise, sauna, whirl bath). Adhesiveness was assessed of the area stuck and the measure of the forces necessary for patch removal using a Peel Patch Tester. Local safety was assessed at 2.0 and 3.5 h. After physical exercise and after sauna, patch adhesiveness was excellent (95%) when applied on the thigh and very good (90%) on the upper arm. Forces of patch removal were significantly lower at 3.5 h than 2.0 h, and at the lower back compared to the other application sites. There were no adverse effects. Slight erythema was observed that was considered to be clinically insignificant. Testopatch was safe and displayed adhesiveness, compatible with physical activities.