Hugo Corstjens

Structural and functional differences in barrier properties of African American, Caucasian and East Asian skin

BACKGROUND Differences in structural and functional skin characteristics have been linked with ethnical background. But racial differences in skin have not been thoroughly investigated by objective methods and the data are often contradictory. OBJECTIVES This study was undertaken to compare skin barrier-related parameters of the stratum corneum on African American, Caucasian and East Asian skin by objective measurements. METHODS Baseline values of trans epidermal water loss were collected on the face. Consecutive stratum corneum D-squame tape strippings were collected on the panelists ventral forearm and face to evaluate skin barrier strength and cohesion. Stratum corneum ceramides, maturation, measured as the transglutaminase-mediated cross-linking of stratum corneum proteins, and stratum corneum trypsin like enzyme activity were measured on the D-squame tape strippings. RESULTS East Asian and to some extent Caucasian skin was characterized by low maturation and relatively weak skin barrier. African American skin was characterized by low ceramide levels and high protein cohesion in the uppermost layers of the stratum corneum. These data can be interpreted in terms of the high prevalence of xerosis in black skin and increased skin sensitivity in East Asian skin. CONCLUSION These results demonstrate that skin properties at the level of the stratum corneum vary considerably among these ethnic groups. This contributes to an improved understanding of physiological differences between these study populations.

Glycation associated skin autofluorescence and skin elasticity are related to chronological age and body mass index of healthy subjects

Glycation is the non-enzymatic reaction between reducing sugars and proteins that leads to the formation of advanced glycation end products (AGEs). In vivo skin autofluorescence (lambda(ex)/lambda(em)=370/440 nm) was used as a non-invasive clinical tool to study skin AGE accumulation in healthy panellists. Using multiple linear regression analysis, it was shown that for panellists below the age of 40, glycation associated in vivo skin fluorescence intensity increased as a function of chronological age and body mass index (BMI). Above the age of 40, the fluorescence was associated to age but not to BMI, suggesting that the effect of age became dominant over BMI. Since the accumulation of AGEs is expected to affect the biomechanical properties of the skin, in vivo skin elasticity data were gathered on a second panel. It was found that skin elasticity depended on age and BMI in a similar fashion as to what we observed for the skin fluorescence data. It is hypothesised that skin AGE accumulation contributes to the loss of skin elasticity in aged and/or overweight people.

Use of the synthetic superoxide dismutase/catalase mimetic EUK-134 to compensate for seasonal antioxidant deficiency by reducing pre-existing lipid peroxides at the human skin surface

The generation of reactive oxygen species (ROS) in UV‐exposed skin is believed to contribute to the photoaging process. The stratum corneum (SC) contains a variety of enzymatic and non‐enzymatic antioxidants to protect against various environmental sources of free radicals. We have previously shown a seasonal variation in SC catalase activity with strong deactivation in sun‐exposed skin in the summer, whereas SC superoxide dismutase (SOD) activity remained intact in those conditions. This potentially leads to the local overproduction of H2O2. The oxidized lipid squalene hydroperoxide accumulates at the surface of sun‐exposed skin in the summer and upon exposure to ultravoilet A (UVA) doses as low as 0.1 J cm−2 and adequate protection against excessive lipid peroxidation at times of UV exposure should be aimed for. We have been using the induction of lipid hydroperoxides at the skin surface by a single dose of UVA (1 J cm−2) as a model system to evaluate the protective effect of antioxidants in vivo. Topical treatment with the synthetic SOD/catalase mimetic molecule (EUK‐134) 1 h before UVA exposure reduced the level of lipid peroxides at the surface of UVA‐exposed skin but also baseline peroxide levels on non‐irradiated skin were reduced in a dose‐dependent fashion. In contrast to alpha‐tocopherol, EUK‐134 even reduced the level of lipid peroxides at the surface of UVA‐exposed skin when it was applied after irradiation. We confirmed that this salen–manganese complex was able to reduce squalene hydroperoxide levels in vitro, suggesting peroxidase‐like activity towards organic peroxides. These data support the concept that the synthetic SOD/catalase mimetic EUK‐134 might be able to compensate for seasonal deficiencies in antioxidant defense capacity at the skin surface, thereby contributing to an optimal protection of the skin against the accumulation of oxidative damage.

Prevention of oxidative damage that contributes to the loss of bioenergetic capacity in ageing skin

Skin ageing is a complex biological process related to a decline in physiological and biochemical performance. A decline in the mitochondrial energy production is a feature of ageing at the cellular level. This is partially attributed to excessive production of reactive oxygen species such as superoxide and hydrogen peroxide in aged individuals. We have investigated the effect of (glyc)oxidative stress on two biochemical targets relevant for the energy metabolism of the skin. First, we showed an age dependent decline in the activity of the hydrogen peroxide detoxifying antioxidant catalase in stratum corneum on a chronically sun-exposed site. Furthermore catalase was sensitive to peroxynitrite-induced in vitro inactivation. Catalase mimetics as well as peroxynitrite scavengers are proposed to maintain hydrogen peroxide detoxification pathways. The second target was creatine kinase, an enzyme that controls the creatine-creatine phosphate shuttle. Creatine kinase lost activity after in vitro glycation by methylglyoxal. This activity loss could be prevented by antiglycation actives. These data suggest that biomolecules involved in energy homeostasis become damaged by different sources of stress. Actives specifically selected for optimal protection against these stress situations will decrease skin vulnerability and prevent the premature loss of skin function.

Morphological characterization of solar lentigines by in vivo reflectance confocal microscopy: a longitudinal approach.

Solar lentigines are benign hyperpigmented skin lesions. Despite their widespread distribution, knowledge on the mechanisms of development is largely unknown. A clinical study was designed in which solar lentigines were characterized using various non‐invasive clinical techniques. A subset of solar lentigines was followed over a 5‐year time period. One hundred and twenty‐eight solar lentigines were evaluated using in vivo reflectance confocal microscopy (RCM) for the evaluation of the length and density of their dermal papillae as well as the deformation of the alignment pattern of hyperrefractive basal cells. Skin colour, colour contrast, the size of the solar lentigo, epidermal proliferation rate, melanin and haemoglobin content were quantified. RCM imaging of solar lentigines revealed a profound structural deformation of the dermal papillae, as the alignment pattern of hyperrefractive basal cells shifted from a circle in non‐lesional skin to an irregular non‐circular shape in solar lentigines. There was a rise in the number of dermal papillae, and these dermal papillae were significantly longer. Solar lentigines had increased melanin and haemoglobin levels and a higher rate of epidermal proliferation. For a subset of nineteen solar lentigines, a longitudinal study was set‐up in which these measurements were repeated 5 years after the first evaluation. The deformation and the number of the hyperrefractive dermal papillary rings increased significantly over the 5‐year time span. The size of the lesion increased, and the skin colour became darker. RCM is a useful non‐invasive clinical tool for the characterization of solar lentigines, in particular the compressive deformation of the dermal papillae. This deformation became more severe over a time period of 5 years. To our knowledge, this is the first time that the in vivo time‐dependent progression of solar lentigines was supported by RCM images, contributing to an improved understanding of the formation and progression of solar lentigines.

Modification of skin discoloration by a topical treatment containing an extract of Dianella ensifolia: a potent antioxidant

Skin hyperpigmentation, and the reactions that precipitate it, have been linked to free radicals by the fact that free radical scavengers or antioxidants can slow that hyperpigmentation. We have screened several hundred plant extracts for antioxidants and discovered one that is both a strong antioxidant and can reduce skin hyperpigmentation. Extracts of Dianella ensifolia contain 1‐(2,4‐dihydrophenyl)‐3‐(2,4‐dimethoxy‐3‐methylphenyl) propane (DP), which was found to inhibit the free radical 1‐1‐diphenyl‐2‐picryl‐hydrazyl (DPPH) with an EC50 value of 78 μm. DP was also found to inhibit Ultraviolet (UV)C‐induced lipid oxidation with an EC50 of about 30 μm. We next investigated the effects of this antioxidant on skin hyperpigmentation. The reduction of discoloration by different topical treatments has been assessed in human volunteers using an in vivo assay for the rate of fading of UVB‐induced tan. Two pharmaceutical formulas containing 4% hydroquinone (HQ) were used as positive controls, and we tested the ability of DP, a plant‐derived amphoteric antioxidant, to increase performance of non‐HQ cosmetic formulations. We found that the cosmetic formula containing DP produced an increase in the rate of fading compared to the two pharmaceutical treatments containing HQ.