Thresholds for the presence of glacial megafauna in central Europe during the last 60,000 years.

Lake sediment records from Holzmaar and the infilled maar of Auel (Eifel, Germany) are used to reconstruct landscape changes and megafauna abundances. Our data document a forested landscape from 60,000 to 48,000 yr b2k and a stepwise vegetation change towards a glacial desert after 26,000 yr b2k. The Eifel landscape was continuously inhabited from 48,000 to 9000 yr b2k by large mammals, documented by the presence of spores of coprophilous fungi from Sordaria and Sporormiella fungi that grow on fecal remains of the megafauna. Megafauna reached higher numbers during cold stadial climates but was present also during the warmer interstadials. Highest abundance was at 56,500/48,500/38,500/33,000/27,000/21,000/16,200/14,000 yr b2k, i.e. under different climate regimes. Some of these dates were associated with clear human presence, which indicates that megafauna was not overkilled by humans. In contrast, human presence could quite likely have been stimulated by the abundant food supply. Megafauna presence decreased significantly when tree abundance increased during interstadials. The Megafauna disappeared finally at 11,400 yr b2k with the development of the early Holocene forest cover, which appears to be the most important threshold for megafauna presence.

A Novel Matrikine-Like Micro-Protein Complex (MPC) Technology for Topical Skin Rejuvenation.

This randomized, controlled, investigator-blinded study performed by an independent research organization evaluated the appearance of periorbital and perioral wrinkles following twice-daily application of a specific blend of matrikines and matrikine-like synthetic peptides for skin rejuvenation over a 6-month period. Fine lines and wrinkles of 133 women, aged 38 years to 65 years, were assessed by an independent expert evaluator using a 5-point visual analogue score. Subjects were divided into 3 groups and randomized to receive either the matrikine-based technology (MPC) or 1 of the 2 materials containing traditional growth factors. Test materials were well tolerated, and all 3 significantly reduced the appearance of periorbital and perioral wrinkles after 3 and 6 months. In the group receiving the matrikine-based technology, periorbital wrinkles improved (≥ 1 unit) in 28% of subjects after 1 month, in 65% after 3 months, and in 81% after 6 months. Perioral wrinkles improved (≥ 1 unit) in 39% of subjects after 1 month, in 41% after 3 months, and in 59% after 6 months. Improvements in skin firmness, tactile roughness, and pore appearance were also observed with each test material. Use of MPC was associated with significantly improved skin elasticity after 2 months (20%) and at 6 months (16%), whereas the comparator materials had no significant effects on elasticity. This study demonstrates that topical use of a specific blend of matrikines and matrikine-like peptides is suitable for skin rejuvenation. It also provides evidence that topical use of this novel technology provides comparable results to other technologies that use traditional growth factors for skin rejuvenation, with an additional potential benefit of improved skin elasticity.

Comparison of a skin-lightening cream targeting melanogenesis on multiple levels to triple combination cream for melasma.

The safety and efficacy of a novel skin-lightening cream (SLC) with 4% hydroquinone (HQ), which additionally contains 4 skin-brightening actives, was compared with a triple combination cream (TCC) with 4% HQ, 0.05% tretinoin, and 0.01% fluocinolone acetonide for the treatment of melasma under measures of sun protection. The study was a randomized, investigator-blinded, split-face study including 20 Caucasian females with at least mild epidermal or mixed melasma. Evaluations were made before treatment, after 4 and 8 weeks, and after 12 weeks at the end of the once-daily treatment period with the creams. The evaluations included the investigator's tolerability assessments, the Investigator's Global Assessment, the Melasma Area and Severity Index (MASI), and a participant questionnaire. Under the conditions of the present study, the SLC was comparable in both efficacy and tolerability with the well-established TCC treatment for facial melasma. The MASI reduction became significant for both creams after 4 weeks and reached -77% for SLC and -79% for TCC cream after 12 weeks of once-daily use under measures of sun protection. None of the subjects discontinued treatment because of an intolerability or adverse event. About one-third of the subjects experienced at least one local intolerability (eg, erythema, dryness, or peeling) with both creams over the entire study period, while the remaining subjects did not experience any intolerabilities.

Efficacy of hydroquinone-free skin-lightening cream for photoaging.

BACKGROUND: Hyperpigmentation and solar damage remains a difficult problem to treat with topical agents. AIMS: To evaluate a novel skin-lightening complex (SLC) comprising four actives targeting melanin formation at multiple levels, namely disodium glycerophosphate, L-leucine, phenylethyl resorcinol, and undecylenoyl phenylalanine, in an oil-in-water emulsion cream. PATIENTS/METHODS: Skin-lightening complex was evaluated in 80 female subjects of skin types I-III with at least moderate mottled hyperpigmentation. After a wash-out period of 1 month with a sunscreen, the subjects added a cream containing the SLC for 12 weeks twice daily to entire face and continued the sunscreen use. RESULTS: Whereas there was no significant change during the wash-out period, the primary endpoint mottled hyperpigmentation decreased by 32% after the 12-week treatment period with the SLC cream. Secondary endpoints such as severity and number of lentigines, skin tone, and skin brightness also improved. In all, 57% of the subjects showed at least a moderate response, 17% did not improve, and 3% got worse after the treatment. CONCLUSIONS: The SLC cream was well tolerated, in particular when comparing with exfoliating or peeling agent containing skin-lightening products. When used with a daily sunscreen, this study confirms that the SLC represents an alternative to hydroquinone, retinoids, and many other skin-lightening actives.

Human skin penetration of a copper tripeptide in vitro as a function of skin layer.

OBJECTIVE AND DESIGN: Skin retention and penetration by copper applied as glycyl-L-histidyl-L-lysine cuprate diacetate was evaluated in vitro in order to assess its potential for its transdermal delivery as an anti-inflammatory agent. MATERIALS AND METHODS: Flow-through diffusion cells with 1 cm(2) exposure area were used under infinite dose conditions. 0.68% aq. copper tripeptide as permeant was applied on isolated stratum corneum, heat-separated epidermis and dermatomed skin and receptor fluid collected over 48 h in 4 h intervals using inductively coupled plasma mass spectrometry to analyze for copper in tissues and receptor fluid. RESULTS: The permeability coefficient of the compound through dermatomed skin was 2.43 ± 0.51 × 10(-4) cm/h; 136.2 ± 17.5 µg/cm(2) copper permeated 1 cm(2) of that tissue over 48 h, while 97 ± 6.6 µg/cm(2) were retained as depot. CONCLUSIONS: Copper as tripeptide was delivered in potentially therapeutically effective amounts for inflammatory disease.

Human skin retention and penetration of a copper tripeptide in vitro as function of skin layer towards anti-inflammatory therapy.

OBJECTIVE AND DESIGN: The skin retention and penetration characteristics of copper applied as glycyl-L-histidyl-L-lysine cuprate diacetate were evaluated in vitro in order to assess the potential for its transdermal delivery as anti-inflammatory agent. MATERIALS AND METHODS: Flow-through diffusion cells with 1 cm(2) exposure area were used under infinite dose conditions. 0.68% aq. Copper as a tripeptide was applied on isolated stratum corneum, on heat-separated epidermis and on dermatomed skin. Receptor fluid collected over 48 h in 4 h intervals was analyzed by inductively coupled plasma mass spectrometry for copper in tissues and receptor fluid. RESULTS: The permeability coefficient of the compound through dermatomed skin was 2.43 ± 0.51 × 10(-4) cm/h; 136.2 ± 17.5 µg/cm(2) copper permeated 1 cm(2) of that tissue over 48 h, while 82 ± 8.1 µg/cm(2) of copper were retained there as depot. CONCLUSIONS: Applied tansdermally as the tripeptide on human skin ex vivo, copper permeated the skin and was also retained in skin tissue in amounts potentially effective for the treatment of inflammatory diseases.

Human stratum corneum penetration by copper: in vivo study after occlusive and semi-occlusive application of the metal as powder.

Aim of the study was to shed light on the long-standing controversy whether wearing copper bangles benefits patients suffering from inflammatory conditions such as arthritis. Sequential tape stripping was implemented on healthy volunteers to examine the diffusion of copper through human stratum corneum in vivo following application of the metal as powder on the volar forearm for periods of up to 72 h. Exposure sites were stripped 20 times and the strips analyzed for metal content by inductively coupled plasma-mass spectroscopy with a detection limit for copper of 0.5 ppb. Untreated skin was stripped in the same fashion, to determine baseline copper levels for comparison with exposure values resulting from exposure in respective volunteers. Under occlusion with exclusion of air, up to 72 h copper values decreased from the superficial to the deeper layers of the stratum corneum with gradients increasing commensurately with occlusion time, characteristic of passive diffusion processes. From the tenth strip on, however, levels reverted to background values. Under semi-occlusion allowing access of air by covering the skin with "breathable" tape, initial copper values lay significantly above baseline values and concentration gradients increased proportionally with occlusion time. At 72 h, from the tenth to the twentieth strip reaching the glistening epidermal layer, copper values continued at constant levels, significantly above baseline values. The results indicate that, in contact with skin, copper will oxidize and may penetrate the stratum corneum after forming an ion pair with skin exudates. The rate of reaction seems to depend on contact time and availability of oxygen. A marked inter-individual difference was observed in baseline values and amounts copper absorbed.

Comparison of cutaneous bioavailability of cosmetic preparations containing caffeine or alpha-tocopherol applied on human skin models or human skin ex vivo at finite doses.

The use of human skin models for performing cutaneous bioavailability studies has been little investigated. For instance, only few studies have been reported on human skin models dealing with vehicle effects on percutaneous penetration. The present study aimed at evaluating the influence on caffeine's and alpha-tocopherol's cutaneous bioavailability of cosmetic vehicles such as a water-in-oil emulsion, an oil-in-water emulsion, a liposome dispersion and a hydrogel applied at finite dose using the reconstructed human skin models EpiDerm and Episkin. The results were compared with those obtained in human skin ex vivo using similar experimental conditions. It was demonstrated that the rank order of solute permeability could be correctly predicted when the preparation was applied at a finite dose in human skin models, at least when solutes with far different physicochemical properties such as caffeine and alpha-tocopherol were used. If only slight effects of cosmetic vehicle on skin bioavailability were observed in human skin ex vivo, they were less predictable using skin models. Especially, alcohol-containing vehicles seemed to behave differently in EpiDerm as well as in Episkin than on human skin ex vivo. Stratum corneum intercellular lipid composition and organization of human skin models differ to some extent from that of human stratum corneum ex vivo, which contributes to less pronounced barrier properties, together with the increased hydration of the outermost stratum corneum layers of the models. These features, as well as still unknown factors, may explain the differences observed in vehicle effects in human skin ex vivo versus human skin models.