Distinct locational differences observable in biophysical functions of the facial skin: with special emphasis on the poor functional properties of the stratum corneum of the perioral region

The face is composed of complicated anatomical components, presenting unique portions, such as the eyes, nose and mouth in a relatively narrow area. Moreover, the facial skin is densely populated by the pilosebaceous units and sweat glands, and its stratum corneum (SC) is much thinner than that of the trunk and limbs, although it is always exposed to the environment. Among various portions of the facial skin, some are more easily irritated than others by environmental stimuli, or are more often affected by certain dermatoses. However, the functional aspects of the different portions of the facial skin have not been studied in detail under a strictly controlled environment in sufficiently large numbers of subjects covering different age groups. Thus, we conducted studies in winter with various biophysical techniques, such as transepidermal water loss (TEWL), as a parameter for SC barrier function, high-frequency conductance as that for skin surface hydration state, skin surface lipids, pH, blood flow and skin surface temperature on the forehead, mid-portion of the cheek (cheek in short), nasal tip (nose in short), nasolabial fold and chin of 20 healthy Japanese females aged 22-37 years (average 25 years) in a climate chamber adjusted to 21 degrees C and 50% relative humidity. Thereafter, we studied the influence of ageing on these biophysical parameters by collecting data of TEWL, high-frequency conductance and size of superficial corneocytes on the cheek, nasolabial fold and chin of 303 healthy Japanese female volunteers of different ages. The obtained results showed that the barrier function of the SC was best on the cheek, presenting the lowest TEWL, which was significantly higher on the nasolabial fold and chin than on the cheek. TEWL showed a decrease with age. In contrast, skin hydration state was higher on the nose, but it tended to be lower on the nasolabial fold, showing a mild age-related increase. The corneocytes on the nasolabial fold and chin were smaller than those on the cheek. They revealed a clear increase in size with age. Skin surface lipids were richest on the nose, whereas the superficial pH on the nose was the lowest among the regions tested. The skin temperature was lowest on the cheek than on other areas of the face; although, together with the nose, its blood flow was higher than that of the others. These data indicate great regional differences observable in SC functions on the face. In general, the SC barrier function increases with age, probably because of a decreased epidermal turnover rate as recognized by the increase in corneocyte size. Among the various sites, the skin of the nasolabial fold and chin, whose SC consisted of the smallest corneocytes, showed poorest SC properties in barrier function, suggesting the presence of mild invisible inflammation. It is understandable that this area easily develops not only the complaint of sensitive skin to cosmetics but also dermatitis because of various external agents.     

In vivo barrier challenge and long‐term recovery in human facial skin

Recently, we developed a biophysical approach to characterize in vivo facial cheek skin as a function of stratum corneum (SC) depth, barrier function and during a 24‐h recovery period. The current study extends this work and characterizes the human facial cheek after barrier challenge and, for the first time, facial SC barrier recovery over a 4‐week period. Changes in the corneocyte size over the 4‐week recovery period, and correlations with changes in Trans‐Epidermal Water Loss (TEWL) were monitored. This approach allows complete characterization of SC barrier function after a full biological regeneration of the SC barrier following tape stripping. The structural and compositional changes in facial cheek were investigated using Attenuated Total Reflectance‐Fourier Transform Infra Red (ATR‐FTIR) spectroscopy, tape stripping, TEWL measurements and image analysis combined with optical microscopy to characterize the SC depth profile during the tape stripping stress and over 4‐week recovery period. TEWL increased significantly from baseline after sequential tape stripping. Corneocyte size decreased with successive tape stripping. An inverse direct correlation was determined between TEWL and corneocyte surface area. After 4 weeks, the corneocyte size and TEWL for the facial cheek recovered 100% from the tape stripping procedure. The in vivo ATR‐FTIR data demonstrated that lipid and sebum components on the surface of the facial cheek SC recovered within 24 h post tape stripping, whereas protein (Amide II) and water components recovered after 1 week.     

Profiling of serine protease activities in human stratum corneum and detection of a stratum corneum tryptase-like enzyme

Seasonal variation in stratum corneum (SC) biophysical and biological characteristics has been described previously. In particular, the winter season has been shown to affect more severely the properties of facial skin compared with forearm skin. Moreover, when compromised, such as in dry skin conditions, facial SC has been shown to contain increased inflammatory cytokines and proteases. Nevertheless, there have been no comparative studies of the activities and depth activity of several proteases in the SC on different body sites and at different times of the year. In this study, we examined the distribution of key serine protease activities (kallikrein 5, kallikrein 7, urokinase, plasmin and a tryptase-like enzyme) in different layers of the SC on the cheek and the forearm by analysis of consecutive tape strippings of healthy Caucasian subjects during winter and summer. The protein content of the tape strippings was quantified by absorption measurements with a recently developed and novel infrared densitometer SquameScan 850A while the SC enzyme activities were determined using fluorogenic peptide substrates. Transepidermal water loss (TEWL), skin pH and skin hydration were higher on the cheek than on the forearm. In the same way, the activity of the inflammatory-related proteases plasmin, urokinase and tryptase was approximately five to eight times and the activity of the desquamatory-related proteases kallikrein 5 and kallikrein 7 approximately two to four times higher on the cheek than on the forearm. There were no gender-related differences in these enzyme activities except for the increased kallikrein 7 in the forearm skin of the female subjects in winter. Reduced kallikrein 5 was associated with increased SC cohesion, as judged by increased protein removal, in forearm skin in the winter months of the year although the skin was clinically normal. It can be concluded that (i) protected skin areas show lower TEWL, skin pH and skin hydration and less protease activities than skin areas that are exposed to the environment, possibly indicating subclinical inflammation on these body sites, (ii) in normal healthy forearm skin, the outer SC exhibits greater serine protease activity than its deeper layers, (iii) compared with the forearm, urokinase- and plasmin-like activities are elevated on SC strippings from the cheek, confirming activation of the plasminogen cascade, and (iv) tryptase-like activity in the SC is also elevated in samples from the cheek, possibly indicating involvement of mast cells in these barrier-compromised body sites or the synthesis of a novel tryptase-like enzyme by keratinocytes. Although elevation of the activities of urokinase, plasmin, kallikrein 5, kallikrein 7 and now a tryptase-like enzyme was observed on SC derived from skin of clinically normal cheeks, we anticipate even higher activities in skin conditions where the epidermal barrier is further impaired.     

Age‐related changes in skin barrier function – Quantitative evaluation of 150 female subjects

The protection against water loss and the prevention of substances and bacteria penetrating into the body rank as the most important functions of the skin. This so‐called ‘skin barrier function’ is the natural frontier between the inner organism and the environment, and is primarily formed by the epidermis. An impairment of the skin barrier function is often found in diseased and damaged skin. An influence of ageing on skin barrier function is widely accepted, but has not been conclusively evaluated yet. Therefore, the aim of this clinical study was to assess the potential influence of ageing on skin barrier function, including transepidermal water loss (TEWL), stratum corneum hydration, sebum content and pH value. One hundred and fifty healthy women aged 18–80, divided into five age groups with 30 subjects each, were evaluated in this study. TEWL, hydration level, sebum secretion and pH value of hydro‐lipid acid film were measured with worldwide acknowledged biophysical measuring methods at cheek, neck, décolleté, volar forearm and dorsum of hand. Whereas TEWL and stratum corneum hydration showed only very low correlation with subject's age, the sebum production decreased significantly with age, resulting in the lowest skin surface lipids levels measured in subjects older than 70 years. The highest skin surface pH was measured in subjects between 50 and 60 years, whereas the eldest age group had the lowest mean pH. The dorsum of the hand was the location with the highest TEWL and lowest stratum corneum hydration in all age groups. The results show that only some parameters related to skin barrier function are influenced by ageing. Whereas sebum production decreases significantly over lifetime and skin surface pH is significantly increased in menopausal woman, TEWL and stratum corneum hydration show only minor variations with ageing.     

Increased basal transepidermal water loss leads to elevation of some but not all stratum corneum serine proteases

There are indications of elevation of some inflammatory serine proteases in barrier damaged skin (e.g. plasmin and urokinase). Moreover, many other serine protease activities are present such as desquamatory enzymes as well as a newly detected tryptase‐like serine protease. However, the activities of these proteases have never been correlated with stratum corneum (SC) barrier function. The activity of extractable key serine proteases (SC trypsin‐like kallikreins, SC chymotrypsin‐like kallikreins, SC tryptase‐like serine protease, urokinase and plasmin) was measured from the outermost layers of SC obtained from facial tape strippings in clinically normal subjects. The protein content of the tape strippings was quantified by absorption measurements with the novel infrared densitometer SquameScan^TM 850A and the protease activities by the use of fluorogenic peptide substrates. SC barrier function, SC hydration and skin surface pH were measured using AquaFlux^TM, NOVA dermal phase meter and Skin‐pH‐Meter^®, respectively. As expected, SC hydration was reduced with increased transepidermal water loss (TEWL) values indicative of barrier impairment. Surprisingly, SC chymotrypsin‐like activity showed no correlation with hydration or TEWL, whereas all other enzymes positively correlated with impaired barrier function and some were statistically significant: SC trypsin‐like kallikreins (R² = 0.66, P < 0.01), SC tryptase‐like enzyme (R² = 0.95, P < 0.001), plasmin (R² = 0.86, P < 0.001) and urokinase (R² = 0.50, P < 0.05). All enzymes except urokinase also negatively correlated with SC hydration. Elevated levels of SC serine proteases have been associated with some dermatological disorders, such as atopic dermatitis, psoriasis and rosacea but these results indicate that these enzymes are also elevated with milder forms of barrier disruption, which is not clinically evident as irritated skin. As these proteases are elevated in the SC, they will also be elevated in the epidermis where they can be involved in neurogenic inflammation and epidermal barrier impairment via activation of the protease‐activated receptors. These results highlight the need for using serine protease inhibitors especially for urokinase and plasmin, SC tryptase‐like serine protease and possibly SC trypsin‐like kallikreins even in milder forms of barrier damage.     

Closed-chamber transepidermal water loss measurement: microclimate, calibration and performance

The importance of transepidermal water loss (TEWL) as a measure of the skin barrier is well recognized. Currently, the open-chamber method is dominant, but it is increasingly challenged by newer closed-chamber technologies. Whilst there is familiarity with open-chamber characteristics, there is uncertainty about the capabilities of the challengers. The main issues are related to how microclimate affects TEWL measurements.
The aim of this paper is to provide a framework for understanding the effects of microclimate on TEWL measurement. Part of the problem is that TEWL measurement is indirect. TEWL is the diffusion of condensed water through the stratum corneum (SC), whereas TEWL methods measure water vapour flux in the air above the SC. This vapour flux depends on (i) the rate of supply of water to the skin surface and (ii) the rate of evaporation of water from the skin surface. Rate (i) is a skin property (TEWL), rate (ii) is a microclimate property. The controlling rate for the combined process is the lower of the above two rates. Therefore, TEWL instruments measure TEWL only when TEWL is the rate-limiting process.
Another problem is that SC barrier property and SC hydration are affected by the microclimate adjacent to the skin surface. This is discussed insofar as it affects the measurement of TEWL. The conclusion is that such changes occur on a timescale that is long compared with TEWL measurement times.
An important aspect of TEWL measurement is calibration. We present an analysis of the traditional wet-cup method and a new droplet method that is traceable and has been independently verified by a standards laboratory.
Finally, we review performance indicators of commercial closed-chamber instruments with reference to open-chamber instruments. The main findings are that TEWL readings correlate well, but there are significant differences in the other aspects of performance.     

Facial skin mapping: from single point bio‐instrumental evaluation to continuous visualization of skin hydration,barrier function,skin surface pH,and sebum in different ethnic skin types

Dry skin is one of the most important concerns of consumers worldwide. Despite huge efforts over several decades, the personal care industry still does not offer a perfect solution to satisfy the unmet needs of consumers for moisturising treatments in different ethnic groups. The paucity of data for the underlying cellular and biochemical problems in, and the effects of moisturisers on photodamaged facial skin may partly explain this. Mainly, single point measurements are used to understand the effects of products on skin physiology even on surrogate skin sites such as the non‐photodamaged volar forearm. Some groups have developed discontinuous facial maps of skin biophysical properties, however, in 2014 a continuous facial analysis of bio‐instrumental evaluations was developed using a heat map approach. These maps enabled a continuous visualization of features that not only revealed an unexpected complexity of facial skin but also indicated that use of surrogate skin sites for facial skin is inappropriate. We have demonstrated that remarkable gradients of skin hydration, TEWL, skin surface pH and sebum exist within short distances across the face and the gradients are distinctive among different ethnic groups. In addition, these studies have demonstrated that darkly‐pigmented individuals do not necessarily have a better skin barrier function than their less‐pigmented counterparts and that Caucasians have a lower facial skin surface pH compared with more pigmented subjects. Overall, there are no correlations between capacitance, TEWL and skin surface pH including individual topology angle values. Novel 3D camera approaches have also been used to facilitate a more precise assignment of measurement sites and visualisation. The 3D facial colour mappings illustrated precisely the local moisturising effects of a moisturising cream. There were subtle ethnic differences in efficacy that may be related to underlying skin biochemistry and/or ethnic differences in product application. A placebo‐controlled study using conductance measurements in Chinese subjects is also reported. Finally, a new whole face statistical approach has been taken to prove differences in skin parameters but also of moisturiser treatment that adds further to our understanding of the ethnic differences in skin physiology and product application. This paper reviews the background of the development and application of this methodology.     

Pores in the epidermis: aquaporins and tight junctions

Water homeostasis of the epidermis is important for the appearance and physical properties of the skin, as well as for water balance in the body. It depends on several factors, e.g. barrier quality, uptake of water into the epidermis, concentration of water-retaining humectants, and external humidity. Aquaporins (AQPs) are pores in the plasmamembranes of cells. Monomeric AQPs form barrel-like structures that are primarily water selective, some AQPs also transport glycerol and possibly other small solutes. In the epidermis, AQP3 is the predominant AQP. It is localized mainly in basal but also in suprabasal layers of the epidermis and is permeable for water as well as for glycerol, a humectant. Mice deficient in AQP3 exhibit reduced stratum corneum (SC) hydration and impaired SC barrier recovery after SC removal. In skin diseases associated with elevated transepidermal water loss (TEWL) and reduced SC hydration, altered expression of AQP3 was shown. Tight junctions (TJ) are cell-cell junctions, which play a central role in sealing the intercellular space of cell sheets and thereby establishing a paracellular barrier. Within the TJ, pores are postulated to exist, which allow the controlled diffusion of water and solutes via the paracellular pathway. In the epidermis, TJ structures were demonstrated in the stratum granulosum whereas TJ proteins were found in all viable layers. Mice which overexpress or are deficient of key-proteins of TJ die soon after birth because of a tremendous TEWL. In various skin diseases that are accompanied by elevated TEWL and reduced skin hydration, staining patterns of TJ proteins are altered. This review will summarize our current knowledge of the involvement of AQPs and TJ in the water homeostasis of the epidermis.     

Significance of hair‐dye base‐induced sensory irritation

Oxidation hair ‐ dyes, which are the principal hair ‐ dyes, sometimes induce painful sensory irritation of the scalp caused by the combination of highly reactive substances, such as hydrogen peroxide and alkali agents. Although many cases of severe facial and scalp dermatitis have been reported following the use of hair ‐ dyes, sensory irritation caused by contact of the hair ‐ dye with the skin has not been reported clearly. In this study, we used a self‐assessment questionnaire to measure the sensory irritation in various regions of the body caused by two model hair‐dye bases that contained different amounts of alkali agents without dyes. Moreover, the occipital region was found as an alternative region of the scalp to test for sensory irritation of the hair‐dye bases. We used this region to evaluate the relationship of sensitivity with skin properties, such as trans‐epidermal water loss (TEWL), stratum corneum water content, sebum amount, surface temperature, current perception threshold (CPT), catalase activities in tape‐stripped skin and sensory irritation score with the model hair‐dye bases. The hair‐dye sensitive group showed higher TEWL, a lower sebum amount, a lower surface temperature and higher catalase activity than the insensitive group, and was similar to that of damaged skin. These results suggest that sensory irritation caused by hair ‐ dye could occur easily on the damaged dry scalp, as that caused by skin cosmetics reported previously.     

Original semiologic standardized evaluation of stratum corneum hydration by Diagnoskin stripping sample

In a normal and healthy skin, the regular elimination of the superficial corneocytes, called desquamation, is a fundamental physiologic process intended to protect the barrier function of the skin. This invisible loss of corneocytes, individually or in small groups, is incessantly compensated by the divisions of the proliferative layer and the upward cellular maturation in order to maintain the harmonious renewal of the epidermis and the integrity of the stratum corneum. The harmony of this desquamation process is intimately conditioned by a sufficient hydration of the stratum corneum: (i) an abnormal desquamation leads to a disruption of the water barrier function and consequently to a dehydration tendency of the stratum corneum, and (ii) a cutaneous dryness (whatever the cause) is able to disturb the desquamation process. Protecting the water content of the stratum corneum has always been a major preoccupation of the cosmetic industry scientists. Consequently, the moisturizing properties of a cosmetic product are objectively measured by various explorations directly targeted on the hydration (corneometry) and on the level of the water barrier function (transepidermal water loss (TEWL) measurements), which depends directly on the skin hydration state. This intimate linkage of the desquamation process and the water content of the stratum corneum enable us to suggest an indirect assessment of the hydration from a direct study of the desquamation by examining a skin-stripping sample (D-Squames) by an optical microscope (linked to a computer). We will describe this already known technique and mainly its new and unpublished semiologic exploitation, named Diagnoskin, whose advantages are its simplicity and its reproducibility particularly interesting in the case of sequential appraisal of dermatologic or cosmetic treatments.     

The influence of a cream containing 20% glycerin and its vehicle on skin barrier properties

Glycerin is widely used in cosmetics and well as in pharmaceutical formulations, mainly as humectant. In vitro studies have shown glycerin to prevent crystallization of stratum corneum model lipid mixture at low room humidity. Whether this may affect the skin barrier function during repeated application of glycerin in a cream base to normal skin is not known. Therefore, the influence of a cream containing 20% glycerin was compared with its placebo cream in a bilateral, double-blind study on 17 healthy volunteers. The effect was evaluated as influence on hydration with a corneometer and on skin barrier function. Skin barrier function was assessed as permeability to water with an evaporimeter (transepidermal water loss; TEWL) and as sensitivity to an irritating surfactant by measuring the biological response (measured as TEWL and skin blood flow). Ten days treatment of normal skin with 20% glycerin significantly increased skin corneometer values, indicating an increased hydration. However, our study failed to show an influence of glycerin on human skin, in terms of TEWL and skin sensitivity to SLS-induced irritation.     

Material design using genetic algorithms and preparation of innovative UV-reflecting composite

The neck is a sun-exposed area. It seems to show the symptoms of photo-ageing as well as facial skin in the elderly. However, the physiological study of neck skin has hardly been reported. We examined the change of skin physiological properties at a neck site with ageing for 61 women (18—69 years old) compared with a cheek site. Water content in stratum corneum (SC) was higher, transepidermal water loss (TEWL) was lower and the turnover rate of SC judged from corneocyte area was slower at the neck site compared with the cheek site. Skin thickness was thinner, skin extensibility and elasticity were higher, skin grooves were deeper, and anisotropy of skin furrows was lower at the neck site than those at the cheek site. It was shown that the neck was also affected by sunlight but not so much as the cheek from the result of gelatinase activity detected in the tape stripped SC. Skin elasticity decreased with ageing at the neck site as well as the cheek site. Fine wrinkles were remarkably increased in the direction of Langer's line with ageing at the neck. Most skin physiological parameters at the neck showed the value between the cheek (heavily sun-exposed area) and back (not sun-exposed area). From these results, it was considered that not only intrinsic ageing but also photo-ageing affected the neck skin. We developed the prototype of cosmetics corresponding to neck skin physiology based on these results, and evaluated the effectiveness of the prototype product by a consumer test including skin measurement for 4 weeks. After treatment, water content increased, and it gave satisfaction in the skin colour brightness, skin elasticity and skin texture improvements for almost all volunteers. It was concluded that the prototype product was useful in neck skin treatment.     

In vivo transepidermal water loss and skin surface hydration in assessment of moisturization and soap effects

Transepidermal water loss (TEWL), skin surface water loss (SSWL) and water content of the stratum corneum are utilized to assess the hydration effects of moisturizers and soaps. The relationship among these parameters may help differentiating hydration obtained via occlusion or by water-holding in the stratum corneum. Furthermore, skin function (hydration, dehydration, barrier damage) can be studied comparing the data obtained with these techniques. In this study, the effects of glycerol, petrolatum, soaps and commercial moisturizers on the skin are investigated and discussed.     

A clinical, biometrological and ultrastructural study of xerotic skin

The purpose of this in vivo study was to investigate, non-invasively on human subjects, xerotic skin and its physiological evolution over time, compared to normal skin. Two groups of 17 female subjects were studied during the winter season, one made up of subjects with normal skin and the other subjects with xerotic skin. A clinical assessment and biometrological measurements of hydration and transepidermal water loss (TEWL) were performed on the same area of the external antero-lateral surface of the leg at the start of the study then after three weeks. At the end of the study, the ultrastructure of stratum corneum samples taken from the same area was examined by transmission electron microscopy. Subjects with xerotic skin were selected according to their impaired cutaneous barrier function, reflected in a TEWL higher than 12 g/m ; 2/h. Compared to normal subjects, they presented a hydration level more than 25% lower. After an interval of 21 days, no significant change in the hydration level or clinical appearance of the xerotic skin was observed. In contrast, the TEWL had decreased significantly (D _ 21- D _ 0=-3.6 g/m ; 2/h; p < 0.001) but still stayed higher than normal values. Changes in the ultrastructure of the stratum corneum were also observed in the subjects with xerotic skin. Unlike normal skin, corneosomes could be detected right up to the surface layers, accompanied by intercellular lipids in an amorphous form. These observations confirm the important roles played by both corneosomes and lipid organization in the cohesion/desquamation processes. In the subjects with normal skin, the hydration level and barrier function remained unchanged during the three week study but an onset of skin dryness was observed, the mean clinical score increasing by +1.3 (p = 0.01). These results confirm that there is no direct relationship between TEWL and the severity of skin dryness. It appears that a clinical evaluation is more sensitive than biometrological measurement for describing early state of cutaneous dryness. This study highlights the importance of a regular cosmetic or dermopharmaceutical treatment during the winter to prevent xerosis apparition on legs.     

Relationship between the average projected area of corneocytes and the onset age of atopic dermatitis in childhood

In childhood, atopic dermatitis typically begins around 2--6 months of age. It is thought that the skin barrier dysfunction as well as allergic disease is important in the mechanism of atopic dermatitis. However, there are few reports of the skin barrier function in childhood. So we examined the relationship between the longitudinal surveys of the skin barrier function through the average projected area of corneocytes (APAc) and clinical findings in children from 1 to 12 months. As a result of examinations, APAc of cheek and upper arm in 1-month-old children is the same as those in adults, and APAc of cheek and upper arm decreases by 6 months of age. These results suggest that the skin barrier function decreases before or after the onset age of atopic dermatitis during childhood. Moreover, we examined APAc of children aged 0–5 for 1 year in the same nursery. APAc of upper arm in atopic dermatitis or atopic disposition has a significant difference compared with that of the other subjects in December. Furthermore, it was shown that change of APAc in the children under medical treatment was correlated with clinical findings. In conclusion, it was thought that the APAc shown as the index of skin barrier dysfunction is associated with the onset age of atopic dermatitis in childhood.     

Ethnic skin types: are there differences in skin structure and function?1

People of skin of colour comprise the majority of the world's population and Asian subjects comprise more than half of the total population of the earth. Even so, the literature on the characteristics of the subjects with skin of colour is limited. Several groups over the past decades have attempted to decipher the underlying differences in skin structure and function in different ethnic skin types. However, most of these studies have been of small scale and in some studies interindividual differences in skin quality overwhelm any racial differences. There has been a recent call for more studies to address genetic together with phenotypic differences among different racial groups and in this respect several large-scale studies have been conducted recently. The most obvious ethnic skin difference relates to skin colour which is dominated by the presence of melanin. The photoprotection derived from this polymer influences the rate of the skin aging changes between the different racial groups. However, all racial groups are eventually subjected to the photoaging process. Generally Caucasians have an earlier onset and greater skin wrinkling and sagging signs than other skin types and in general increased pigmentary problems are seen in skin of colour although one large study reported that East Asians living in the U.S.A. had the least pigment spots. Induction of a hyperpigmentary response is thought to be through signaling by the protease-activated receptor-2 which together with its activating protease is increased in the epidermis of subjects with skin of colour. Changes in skin biophysical properties with age demonstrate that the more darkly pigmented subjects retaining younger skin properties compared with the more lightly pigmented groups. However, despite having a more compact stratum corneum (SC) there are conflicting reports on barrier function in these subjects. Nevertheless, upon a chemical or mechanical challenge the SC barrier function is reported to be stronger in subjects with darker skin despite having the reported lowest ceramide levels. One has to remember that barrier function relates to the total architecture of the SC and not just its lipid levels. Asian skin is reported to possess a similar basal transepidermal water loss (TEWL) to Caucasian skin and similar ceramide levels but upon mechanical challenge it has the weakest barrier function. Differences in intercellular cohesion are obviously apparent. In contrast reduced SC natural moisturizing factor levels have been reported compared with Caucasian and African American skin. These differences will contribute to differences in desquamation but few data are available. One recent study has shown reduced epidermal Cathepsin L2 levels in darker skin types which if also occurs in the SC could contribute to the known skin ashing problems these subjects experience. In very general terms as the desquamatory enzymes are extruded with the lamellar granules subjects with lowered SC lipid levels are expected to have lowered desquamatory enzyme levels. Increased pores size, sebum secretion and skin surface microflora occur in Negroid subjects. Equally increased mast cell granule size occurs in these subjects. The frequency of skin sensitivity is quite similar across different racial groups but the stimuli for its induction shows subtle differences. Nevertheless, several studies indicate that Asian skin maybe more sensitive to exogenous chemicals probably due to a thinner SC and higher eccrine gland density. In conclusion, we know more of the biophysical and somatosensory characteristics of ethnic skin types but clearly, there is still more to learn and especially about the inherent underlying biological differences in ethnic skin types.     

Caffeine improves barrier function in male skin

The influence of androgens, especially testosterone and its effector dihydrotestosterone, results in a constitutive disadvantage for male skin, e.g. reduced viability of hair at the scalp and reduced epidermal permeability barrier repair capacity. Dihydrotestosterone can act, among others, as an adenyl cyclase inhibitor. Caffeine on the other hand is an inexpensive and (in regular doses) harmless substance used in various cosmetic products, which can act as a phosphodiesterase inhibitor. To prove the hypothesis that caffeine as a phosphodiesterase inhibitor is able to override testosterone-induced effects on barrier function, we performed a double-blind placebo controlled study with healthy volunteers. In this study, 0.5% caffeine in a hydroxyethylcellulose gel preparation (HEC) was applied on one forearm, HEC without caffeine on the other forearm of male and female volunteers for 7 days and transepidermal water loss (TEWL) was measured before and at the end of the treatment period. Basal TEWL did not differ significantly between male and female subjects but the application of caffeine significantly reduced TEWL in male skin compared with female skin. We conclude that caffeine is beneficial for barrier function in male skin.     

Assessment of the variation of skin barrier function with anatomic site,age, gender and ethnicity

The skin is the largest organ of the human body and its functions include protection, thermoregulation sensation and secretion. Significant advances in our understanding of how the morphology and physiology of the skin contribute to the skin’s barrier role have been achieved in recent years. The aim of this review is to summarize the principal approaches which have been used to assess variation in skin barrier function with anatomic site, age, gender, and ethnicity. The methods discussed include trans‐epidermal water loss (TEWL) measurement, assessment of corneocyte size, response to vasoactive compounds and attenuated total reflectance Fourier transform infrared (ATR‐FTIR) interrogation of skin. The utility of the various methods is considered and the most important findings in the literature to date are highlighted.     

Characterization of the barrier function in a reconstituted human epidermis cultivated in chemically defined medium

The aim of the study was to characterize and assess the maturation process of the barrier function in a reconstituted human epidermis (REp) cultivated in a chemically defined medium. For this purpose histo-morphological analysis, percutaneous absorption studies and non-invasive measurements were performed. In order to understand the time course of the barrier development, REp cultivated from the same pool of normal human keratinocytes were harvested and measured after several increasing periods of exposure at the air–liquid interface. From these results we concluded that a maturation period of at least 16 days at the air–liquid interface was required for an optimal barrier function development of REp. At this time point, the permeability of the skin cultures for caffeine (CAF) was 20–25-fold higher than that of normal human skin (NHS) biopsies. Non-invasive measurements of skin water content, transepidermal water loss (TEWL) and pH were achieved after the same period of time. Results showed that the stratum corneum (SC) of REp was slightly more hydrated than that of ex vivo and in vivo , human skin. TEWL was slightly higher through REp than through NHS, and the pH of the REp models was very close to that of in vivo , normal human skin. In the latter part, assuming that this type of model could be routinely used, we quantified over a 1-year period the barrier function variability of this skin culture model between batches. The satisfactory results obtained with a 20% coefficient of variation indicated that this REp model has a consistent and reproducible barrier function. This leads us to suggest that the skin model might be considered an alternative membrane to normal human skin for permeation screening tests.     

Skin lipids

Concepts regarding the structure and function of the stratum corneum (SC) have changed from that of a tough film of loosely adherent cells to that of a two-compartment system of protein-enriched cells embedded in intercellular lipids. The two-compartment arrangement enlarged the role of epidermal lipids from that of the plasticizing component of the SC to that of the epidermal barrier governing water-holding properties as well as take-up of water, the differences in permeability of topically applied lipophilic and hydrophilic agents as well as cohesion and desquamation of the SC. Barrier properties of SC are dependent largely on the intactness of the lipid lamellae that surround the corneocytes. The pliability of the SC depends on a correct balance of lipids, hygroscopic water-soluble substances and water.
Mammalian differentiation involves characteristic changes in lipid composition consistent with the requirements for waterproofing. There is a progressive depletion of phospholipids and glycosphingolipids with enrichment in ceramides, cholesterol, free fatty acids, and small amounts of other polar (e.g. cholesterol sulphate) and non-polar species (e.g. hydrocarbons, cholesterol esters, triglycerides). The sphingolipids account for the most lipid by weight and are presumed to be of major importance for the water-retaining properties of the epidermal barrier. Decrease of sphingolipid content occurs in aged skin. Deficiency of essential fatty acids leads to enhanced transdermal water transport in addition to dryness and scaliness of the skin. A mixture of both saturated and unsaturated fatty acids produces the optimal barrier to water loss from the SC. The balance between solid crystal and liquid crystalline phases in epidermal lipids is determined by the degree of fatty acid unsaturation and the amount of water.