Baby care product development: artificial urine in vitro assay is useful for cosmetic product assessment.

As a result of infants' inability to control urination, the skin of the diaper area has special needs for protection from irritating effects of urine and prevention of diaper dermatitis such as products for cleansing and protection of the skin. Several in vitro models are currently available to assess tolerance. In vitro testing using artificial urine allows the protective effects of diaper-region cosmetics to be ascertained. Thus, a new model defined as "artificial urine in vitro assay" has been added to our traditional pre-clinical in vitro testing program. IL1-α is a highly active and pleiotropic pro-inflammatory cytokine. It plays a key role in inflammation and is the biological mirror of irritation induced by diaper dermatitis. This study determines, on human skin explants, if a cosmetic formula is (1) tolerated equally as well in the presence of artificial urine as in its absence and (2) is able to decrease IL1-α production induced by artificial urine or Sodium Dodecyl Sulfate. 31 tests including 17 in-house formulas, 10 bench-markers and 4 combinations of products were performed and data obtained are represented on a simple four-point scale (from practically non protective to very protective). It allows determination of formula-type groups that will have predictable protective properties in subsequent clinical trials and comparison with competitors' products. It is a useful aid in the formulation stage and provides readily-useable data for the cosmetic risk assessment.

Association between collagen production and mechanical stretching in dermal extracellular matrix: in vivo effect of cross-linked hyaluronic acid filler. A randomised, placebo-controlled study.

BACKGROUND: The effects of hyaluronic acid (HA) injection on tissue collagen anabolism are suggested to be related to the induction of mechanical stress, causing biochemical changes in skin physiology. OBJECTIVES: To ascertain the association between dermal mechanics modulated by a hyaluronic acid-based filler effect and metabolism. METHODS: Sixty females were randomised to receive a 0.5mL injection of HA gel or isotonic sodium chloride (control) in the arm. Skin biopsies were taken at baseline and after 1, 3 and 6 months. Protein and gene expression of procollagen, matrix metalloproteinases (MMP) and MMP tissue inhibitors (TIMP1) were measured blind by ELISA and qPCR, respectively. Injected volumes were measured by high-frequency ultrasound and radiofrequency analysis. Skin layer effects of injections were analysed by finite element digital modelling. RESULTS: One month after injection, the filler induced an increase in procollagen (p=0.0016) and TIMP-1 (p=0.0485) levels and relative gene expression of procollagen III and I isoforms compared with the controls. After 3 months, procollagen levels remained greater than in the controls (p=0.0005), whereas procollagen expression and TIMP-1 and MMP content were no longer different. Forty-three percent of the injected filler volume was found at 1 month, 26% after 3 months and 20% after 6 months. LIMITATIONS: The ultrasound imaging technique limited the scope of the investigation and precluded an evaluation of the action of the filler at the hypodermic level. CONCLUSIONS: Integrating both mechanical and biological aspects, our results suggest that mechanical stress generated by cross-linked HA plays a role in dermal cell biochemical response.

Quantification of Demodex folliculorum by PCR in rosacea and its relationship to skin innate immune activation.

The aim of this study is to quantify D. folliculorum colonisation in rosacea subtypes and age-matched controls and to determine the relationship between D. folliculorum load, rosacea subtype and skin innate immune system activation markers. We set up a multicentre, cross-sectional, prospective study in which 98 adults were included: 50 with facial rosacea, including 18 with erythematotelangiectatic rosacea (ETR), and 32 with papulopustular rosacea (PPR) and 48 age- and sex-matched healthy volunteers. Non-invasive facial samples were taken to quantify D. folliculorum infestation by quantitative PCR and evaluate inflammatory and immune markers. Analysis of the skin samples show that D. folliculorum was detected more frequently in rosacea patients than age-matched controls (96% vs 74%, P < 0.01). D. folliculorum density was 5.7 times higher in rosacea patients than in healthy volunteers. Skin sample analysis showed a higher expression of genes encoding pro-inflammatory cytokines (Il-8, Il-1b, TNF-a) and inflammasome-related genes (NALP-3 and CASP-1) in rosacea, especially PPR. Overexpression of LL-37 and VEGF, as well as CD45RO, MPO and CD163, was observed, indicating broad immune system activation in patients with rosacea. In conclusion, D. folliculorum density is highly increased in patients with rosacea, irrespective of rosacea subtype. There appears to be an inverse relationship between D. folliculorum density and inflammation markers in the skin of rosacea patients, with clear differences between rosacea subtypes.

Pharmacological properties of Myrtacine® and its potential value in acne treatment.

This study aimed at evaluating the antiproliferative, antibacterial, and anti-inflammatory properties of an ethanolic myrtle extract (Myrtacine®) in vitro, characterising its potential active compounds (myrtucommulones A and B') by structural analysis, and evaluating their biological activity. Antiproliferative activity was assessed by the BrdU incorporation assay in HaCat keratinocytes and inhibitory and bactericidal activities against P. ACNES strains by measuring the minimal inhibitory concentration (MIC) and D value. Anti-inflammatory effect was evaluated by measuring 6-keto-prostaglandin F1 α and [³H]-arachidonic acid metabolite production in keratinocytes stimulated for inflammation. Myrtacine® inhibited keratinocyte proliferation by 27 % and 76 % at 1 and 3 µg/mL, respectively (p < 0.001). A comparable effect, though less marked, was observed with 5 µg/mL myrtucommulones A and B' (-36 % and -28 %, respectively). Myrtacine® inhibited erythromycin-sensible and -resistant P. ACNES strains growth with MICs of 4.9 µg/mL and 2.4 µg/mL, respectively. Myrtucommulone B' and myrtucommulone A displayed a similar inhibitory activity against both strains (for both strains, MIC = 1.2 µg/mL and about 0.5 µg/mL, respectively). At 3 and 10 µg/mL, Myrtacine® significantly decreased all metabolite production from cyclooxygenase (81 % and 107 %, p < 0.0001) and lipoxygenase (52 % and 95 %, p < 0.001) pathways. Finally, Myrtacine® exhibited a concentration-dependent anti-lipase activity at 100 µg/mL and 1 mg/mL, as it decreased lipase activity by respectively 53 % and 100 % (p < 0.01 for both). In conclusion, in vitro, Myrtacine® demonstrated antiproliferative, antibacterial, and anti-inflammatory properties that may be of value to exert a global action in the treatment of acne lesions.

Assessment of the clinical efficacy of a hyaluronic acid-based deep wrinkle filler using new instrumental methods.

BACKGROUND: The efficacy of numerous hyaluronic acid (HA)-based fillers has been demonstrated by semi-quantitative and qualitative methods, useful in clinical practice, but poorly reliable. OBJECTIVE: To objectively evaluate the efficacy of a HA gel in treating nasolabial folds (NLFs) over a 9-12-month follow-up period. METHODS: A total of 47 adult patients with moderate to severe NLFs received one or two injections of HA gel. Efficacy was assessed by measuring NLF depth at time intervals up to 12 months subjectively by blind and open clinical scoring using the Lemperle scale, and objectively using skin replicas and in vivo 3D imaging methods. Tissue characterization and dermal thickness were also assessed using radiofrequency ultrasonography and high-resolution ultrasound imaging, respectively. RESULTS: The filler injection highly significantly decreased the depth of NLFs (p < 0.0001) at all time points, with an improvement of at least 1 grade in the Lemperle score in 77% and 89% of the subjects at 9 and 12 months, respectively. NLF volume measured on replicas and 3D images significantly decreased after injection and this improvement was maintained over 12 months. CONCLUSION: This HA gel is well tolerated and provides a significant and long-lasting correction of moderate to severe NLFs, as objectively demonstrated by instrumental methods.

Comparison of perceived itch induced by skin prick-tests with histamine and codeine.

The role of personal factors makes it difficult to correlate subjective data, such as those obtained with the use of a visual analogue scale, and objective data, such as a quantity of injected histamine. In this study, prick tests with histamine and codeine on the forearms allowed a coherent variation in itch scores to be obtained over time, with highly significant differences from controls and with a peak at 4 minutes. These tests are therefore valuable for screening anti-pruritic agents. A significant difference between initial scores and scores for new prick tests after 7 days suggest that tachyphylaxis persists.

Geometrical capillary network analysis.

BACKGROUND: Skin microcirculation, especially the superficial network, can be assessed by a computer capillary video microscope system. The study of morphology and dynamics of microcirculation must include all dynamic and cooperative processes between the capillaries. For characterizing capillary ensembles, the statistical and geometrical properties of the network need to be explored. METHODS: The microvaculature of the skin and the microcirculation were investigated by combining videocapillaroscopy (VCP) and image processing techniques based on computational geometry and graph theory. Our goal was to characterize the capillary network in noisy pictures of the scalp. Different geometric methods were developed, based on proximity parameters (distance and surface) in order to circumscribe and construct this network. RESULTS: By studying the distribution of these parameters, extreme values or outliers, which usually correspond to artifact subregions in the pictures could be eliminated. Different algorithms were developed and has been implemented in an image processing software (Capilab Toolbox). CONCLUSION: This computerized system is capable of real-time processings, increasing the quality of videocapillaroscope images and minimizing the disturbance of artifacts. The algorithms presented here are easy to implement and can process any kind of images of the skin, even in the scalp. In association with an example-based detection system, this method can be generalized to other stimuli in the same conditions.