Thiamidol containing treatment regimens in facial hyperpigmentation: An international multi-centre approach consisting of a double-blind, controlled, split-face study and of an open-label, real-world study.

OBJECTIVE: Tyrosinase is the rate-limiting enzyme in melanogenesis. Thiamidol is the most potent inhibitor of human tyrosinase out of 50 000 tested compounds. In clinical studies, it was shown to improve facial hyperpigmentation, post-inflammatory hyperpigmentation and age spots significantly. To identify the optimal number of daily Thiamidol applications, we conducted a split-face study comparing the efficacy and tolerability of four-times with two-times daily application. Subsequently, we evaluated the efficacy and tolerability of a typical face care regimen containing Thiamidol in a real-world study. METHODS: The split-face study was double-blind, randomized, controlled, including two Thiamidol containing products (serum and day care SPF 30). The serum was applied twice daily on one half of the face and the day care SPF30 twice-daily on the whole face. The real-world study was open-label, observational, including three Thiamidol containing products (day care SPF 30 in the morning, serum and night care in the evening). In both studies, subjects with mild-to-moderate facial hyperpigmentation applied the products over 12 weeks. Assessments included clinical and subjective grading of hyperpigmentation, skin condition, hemi-/modified MASI, chromameter and clinical photography. RESULTS: In the split-face study (n = 34), hyperpigmentation, skin roughness and hMASI improved all significantly (P < 0.001) versus baseline, with first visible results after two weeks of twice-daily application. The four-times daily application led to significant improvement versus the two-times daily application. In the real-world study (n = 83), all evaluated parameters, including skin condition and chromametry (n = 30), improved significantly (P < 0.001) in comparison with baseline and the corresponding preceding visits. The subjects judged the cosmetic properties of the products positively. In both studies, the products were well tolerated. CONCLUSION: Four-times daily Thiamidol improves facial hyperpigmentation significantly more than two-times daily and is well tolerated by the subjects. The real-world study with a typical face care regimen containing Thiamidol shows improvement of facial hyperpigmentation and confirms tolerability. Furthermore, the data provide evidence for the suitability of this three-product Thiamidol regimen for day-to-day life.

OBJECTIF: La tyrosinase est l'enzyme qui limite le taux de mélanogénèse. Le Thiamidol est le plus puissant inhibiteur de la tyrosinase humaine parmi les 50 000 composés testés. Lors d'études cliniques, il a été démontré qu'il améliore de manière significative l'hyperpigmentation du visage, l'hyperpigmentation post-inflammatoire et les taches de vieillesse. Afin d'identifier le nombre optimal d'applications quotidiennes de Thiamidol, nous avons mené une étude hémi-visage comparant l'efficacité et la tolérance d'une application quatre fois par jour à une application deux fois par jour. Par la suite, nous avons évalué l'efficacité et la tolérance d'un régime de soins du visage typique contenant du Thiamidol dans le cadre d'une étude en situation réelle. MÉTHODES: L'étude hémi-visage était en double aveugle, randomisée et contrôlée, incluant deux produits contenant du Thiamidol (sérum et soin de jour SPF 30). Le sérum a été appliqué deux fois par jour sur une moitié du visage, et le soin de jour SPF30 deux fois par jour sur l'ensemble du visage. L'étude en situation réelle était ouverte, observationnelle, et comprenait trois produits contenant du Thiamidol (soin de jour SPF 30 le matin, sérum et soin de nuit le soir). Dans les deux études, les sujets présentant une hyperpigmentation faciale légère à modérée ont appliqué les produits pendant 12 semaines. Les évaluations comprenaient une évaluation clinique et subjective de l'hyperpigmentation, de l'état de la peau, du hémi/modifié MASI, du chromamètre et de la photographie clinique. RÉSULTATS: Dans l'étude hémi-visage (n = 34), l'hyperpigmentation, la rugosité de la peau et l'hMASI se sont tous améliorées de manière significative (P < 0.001) par rapport à la ligne de base, avec des effets devenus visibles aprés deux semaines d'application deux fois par jour. L'application quatre fois par jour a apporté une amélioration significative par rapport à l'application deux fois par jour. Dans l'étude en situation réelle (n = 83), tous les paramѐtres évalués, y compris l'état de la peau et la chromamètrie (n = 30) se sont améliorés significativement (P < 0.001) par rapport à la ligne de base et aux visites précédentes correspondantes. Les sujets ont jugé positivement les propriétés cosmétiques des produits. Dans les deux études, les produits ont été bien tolérés. CONCLUSION: L'application de Thiamidol quatre fois par jour, améliore l'hyperpigmentation du visage de maniѐre plus significative que deux fois par jour et est bien toléré par les sujets. L'étude en situation réelle avec un régime de soins du visage typique contenant du Thiamidol montre une amélioration de l'hyperpigmentation faciale et confirme la tolérance. En outre, les données fournissent des preuves de l'adéquation de ce régime de trois produits à base de Thiamidol pour le soin quotidien.

Prevention of follicular penetration: barrier-enhancing formulations against the penetration of pollen allergens into hair follicles.

The hair follicles could be a reservoir for topically applied substances. They are not only surrounded by a close network of blood capillaries, which makes them interesting for drug delivery, but they are also the host of dendritic cells, which are important for immunomodulation. Previously, pollen allergens were shown to penetrate into the hair follicles. The application of barrier-enhancing formulations might represent an effective strategy to prevent pollen protein penetration into the hair follicle. In the present study, porcine skin areas were pretreated with 4 barrier-enhancing emulsions. One skin area served as control and remained without pretreatment. Afterwards, fluorescein-isothiocyanate-labeled grass pollen proteins were applied to the porcine skin samples, and their penetration was investigated via fluorescent laser scanning microscopy. It was shown that the barrier-enhancing formulations were able to significantly reduce the penetration of exogenous proteins into the hair follicles, the extent of such reduction depending on the formulation.

Hepatic gene expression patterns in thyroid hormone-treated hypothyroid rats.

Thyroid hormone (T3) is essential for normal development, differentiation and metabolic balance. We have performed DNA microarray experiments using hepatic RNA from hypothyroid and T3-treated hypothyroid rats in order to characterize T3-induced gene expression patterns after various time points (6, 24 and 48 h after the administration of the hormone). Sixty-two of 4608 different genes displayed a reproducible T3-response, and cluster analysis divided these differentially regulated genes into six expression patterns. Thirty-six genes were not significantly regulated within the first 24 h. Transient transfection experiments of eight late-induced gene promoters failed to detect a thyroid hormone response element within their regulatory elements, suggesting an indirect activation mechanism(s). In search for an intermediate factor of T3 action, we examined whether various rather ubiquitous transcription factors, peroxisome proliferator-activated receptors (PPARs) and coactivators of the PPARgamma coactivator 1 family (PGC-1) are regulated by T3. Only PPARgamma and PERC/PGC-1beta exhibit a significant T3-response within the first 6 h after treatment, identifying these factors as candidate components for mediating the late-induced expression pattern. Regulation of early-induced genes within the first 6 h after administration of T3 on transcript levels correlates with altered protein levels after 24 and 48 h in vivo.

Anti-inflammatory efficacy of topical preparations with 10% hamamelis distillate in a UV erythema test.

In 40 volunteers the efficacy of three lotions with 10% hamamelis distillates from different suppliers, two vehicles, dimethindene maleate 0.1% gel, hydrocortisone 1% cream and hydrocortisone 0.25% lotion were investigated in a modified UV erythema test with three UV dosages (1.2, 1.4 and 1.7 MED). The test preparations were applied occlusively over a 48-hour period following irradiation. Chromametric measurement of redness and visual assessment were performed 24, 48 and 72 h after induction of erythema. The hydrocortisone formulations were most effective in erythema suppression. An anti- inflammatory effect was noted for all three hamamelis lotions as well as for the vehicles. A significantly greater suppression of erythema than seen with the vehicles was noted for one of the hamamelis lotions at 1.4 MED. The efficacy of the antihistamine dimethindene maleate did not surpass the hamamelis lotions or the vehicles. Even though the differences between the hamamelis lotions were slight, it was possible to make an objective selection of the best hamamelis distillate for aftersun purposes.

Topical activity of ascorbic acid: from in vitro optimization to in vivo efficacy.

We present here a new cosmetic formula system containing 3% ascorbic acid based on an optimized oil-in-water (O/W) emulsion. This formulation demonstrated a good long-term stability of the active ingredient and also of the emulsion itself. It could be deduced from in vitro release studies that this O/W emulsion enabled a better release of the hydrophilic active agent than an alternative W/O emulsion. By measuring the ultraweak photon emission, which is a well-established parameter for the oxidative stress in the skin, the high in vivo antioxidant capacity of 3% ascorbic acid was demonstrated after 1 week of product application. This placebo-controlled study also proved that ascorbic acid in an O/W cream reduced oxidative stress in human skin significantly better than the derivative sodium ascorbyl-2-phosphate, a more stable vitamin C replacement commonly used in cosmetic formulations. With increasing age, the number of papillae in the epidermal-dermal junction zone in human skin are reduced. This implies a possible consequence of reduced mechanical resistance of the skin and impaired supply of the epidermis with nutrients. In a 1-month placebo-controlled study on 25 human volunteers, a significant increase in the number of dermal papillae after application of the 3% ascorbic acid cream was demonstrated, using a confocal laser scanning microscope. Fine lines and wrinkles are a characteristic sign of aged and especially photo-aged skin. Application of 3% ascorbic acid in a 12-week placebo-controlled usage study indicated a significant reduction of facial wrinkles. Altogether, 3% ascorbic acid in a cosmetic O/W emulsion has been shown to be appropriately stable and to enable a good release of the active agent in vitro as a precondition for a high efficacy in vivo. Application in vivo resulted in a significant reduction of oxidative stress in the skin, an improvement of the epidermal-dermal microstructure and a reduction of fine lines and wrinkles in aged skin. These results were received within a relatively short period of time of product application.