Development of the stratum corneum.

In 2015, Professor Ronald (Ronnie) Marks will celebrate his 80th birthday and the 35th year since assuming the Chair of Dermatology at the University of Wales College of Medicine in Cardiff, Wales. Ronnie's long and prolific career is well deserving of a celebratory Festschrift. Among his many accomplishments, Marks was an early champion of quantitative measurements and the application of bioengineering methods to clinical skin science, with particular focus on stratum corneum biology and the measurement of skin appearance. Appealing to Ronnie's wry sense of humour, I would characterize his career in the words of the native Welshman, Dylan Thomas, who published an unfinished novel in 1955 entitled Adventures in the Skin Trade. Ronnie Marks has been a quintessential and imaginative adventurer in the 'skin trade', and he continues to forge new trails for others to follow. The areas highlighted below are emblematic of Ronnie's varied research interests and his impact on stimulating experimental questions for me and future investigators of epidermal differentiation and stratum corneum development.

Role of TNF-α polymorphism -308 in neurosensory irritation.

Neurosensory cutaneous discomfort in response to topical products is common, yet the relationship between symptoms such as stinging and visible irritation is currently unclear. The presence of a polymorphism at position -308 on the TNF-α gene has been associated with skin irritation, i.e., erythema, dryness. Individuals with a G to A transition (AA/GA genotypes) have a lower threshold to experimentally induced irritation than those with the wild type (G allele, GG genotype). We investigated the effect of this polymorphism on neurosensory irritation (NSI). DNA genotyping was used to determine the allele type amongst a population of health care workers. The neurosensory response to lactic acid and water on the nasolabial folds and hands was assessed using a quantitative lactic acid sting test. Both genotypes had a more intense response to lactic acid compared with water on the face. The AA/GA genotypes had directionally higher scores from lactic acid (P = 0.1) and significantly higher stinging intensities from water (P = 0.001) on the face. For the hands, stinging intensities were higher for lactic acid and water amongst the AA/GA genotypes (P = 0.03 and 0.006 respectively). NSI to lactic acid was significantly higher on the face than on the hands (P < 0.05). Our findings indicate that subjects with the A transition at position -308 on the TNF-α gene experience more intense NSI with common ingredients, i.e., lactic acid and water, than those with the wild type. TNF-α polymorphism -308 may account for some of the inter-individual variability in response to skin care practices.

The biology of vernix caseosa.

The biology and physical properties of the uniquely human skin cream 'vernix caseosa' are discussed. This material coats the foetal skin surface during the last trimester of gestation and provides multiple beneficial functions for the foetus and newborn infant. Vernix has a complex structure similar to stratum corneum but lacks lipid lamellae and is more plastic due to the absence of desmosomal constraints. In utero, vernix is made in part by foetal sebaceous glands, interacts with pulmonary surfactant, detaches into the amniotic fluid, and is swallowed by the foetus. At the time of birth, vernix has a remarkably constant water content approximating 80%. Postnatally, vernix is simultaneously a cleanser, a moisturizer, an anti-infective, and an anti-oxidant. Vernix facilitates acid mantle development and supports normal bacterial colonization. Its hydrated cellular structure and unusual lipid composition provide a 'best' solution for the needs of the foetus and newborn, not least of which is the attraction of caregivers. Vernix is an important natural biomaterial of potential interest to cosmetic scientists, and other disciplines involved in product development and therapies targeting the complex interface between the stratum corneum and a changing terrestrial environment.

A novel role for vernix caseosa as a skin cleanser.

OBJECTIVES: Skin cleansing is a complex process involving endogenous and exogenous mechanisms. This study examines the role of vernix caseosa in the process of skin cleansing in the perinatal period. METHODS: Vernix was evaluated as an exogenously applied skin cleanser using digitized image analysis which quantified residual carbon particles following a standardized cleansing assay. In addition, the detachment of vernix from human cadaveric skin and Gore-Tex supports was investigated following timed exposures to a variety of commonly used commercial surfactants. Detachment was quantified spectrophotometrically as increased turbidity at 650 nm. RESULTS: Image analysis showed that exogenous application of vernix exhibited a cleansing capability comparable or superior to standard skin cleansers. Dose-dependent increases in solution turbidity (vernix detachment) were seen following exposure of vernix-covered Gore-Tex vehicles to sodium laureth sulfate, sodium lauryl sulfate, and cocamidopropyl betaine solutions. Similar results were seen with cadaveric skin. CONCLUSIONS: These results demonstrate a role for vernix caseosa as a skin cleanser. Previous views of vernix as a soil or skin contaminant at birth need to be reevaluated.

Surface free energy characterization of vernix caseosa. Potential role in waterproofing the newborn infant.

BACKGROUND/AIMS: Vernix caseosa is a proteolipid biofilm synthesized by the human fetus, which progressively covers the fetal skin surface during the last trimester of pregnancy. The exact physiological functions of vernix are unclear. Hypothetically, it serves a role in "waterproofing" the fetus during the critical period of epidermal barrier development before birth. Vernix may also play a role in adaptation of the fetal skin surface to the dry, cool extrauterine environment after birth. Given the strategic position of vernix on the fetal skin surface and the rapidly changing environment encountered by the skin at birth, we proposed that investigation of vernix surface characteristics would facilitate understanding its putative physiological roles. METHODS: In this paper, we focused on the determination of the surface free energy (SFE) of vernix caseosa. Different approaches were used to calculate the SFE of vernix from contact angle (theta) measurements between vernix and various liquids (benzyl alcohol, diiodomethane, glycerol, and water). The critical surface tension (CST) of vernix was calculated using Zisman plots. The dispersive and the polar components of vernix SFE were calculated using the Owens-Wendt geometric mean method. Vernix was contrasted with petrolatum, a commonly used skin protectant. RESULTS: CST of fresh vernix was 40.5 dyne/cm while that of petrolatum was 35.8 dyne/cm. Fresh vernix polar SFE was 1.5 dyne/cm while petrolatum had almost no polar SFE component (0.03 dyne/cm). For all liquids (except the nonpolar diiodomethane) there was a significant decrease in contact angle with time. CONCLUSIONS: The CST and the total SFE values suggest that vernix has very low surface energy and is highly unwettable. These findings are significant insofar as the main component in vernix is water, which is highly energetic. Although vernix has a very high water content, the major part of its SFE is hydrophobic (dispersive). The limited interaction between vernix and hydrophilic liquids supports the hypothesis that vernix acts as a natural protectant cream to "waterproof" the fetus in utero while submerged in the amniotic fluid.

Effect of semipermeable membranes on skin barrier repair following tape stripping.

Reports in the literature suggest that the permeability of a wound dressing to water transport is an important variable in the healing of superficial wounds. Factors that influence skin hydration during barrier repair, therefore, are important in the optimization of wound treatments. In this study, the effects of semipermeable films on human skin following a standardized wound (tape stripping) were evaluated using measurements of transepidermal water loss (TEWL), skin hydration, rate of moisture accumulation, and erythema. Wounds treated with semipermeable films underwent more rapid barrier recovery than either unoccluded wounds or wounds under complete occlusion. Barrier films that produced intermediate levels of skin hydration during recovery produced the highest barrier repair rates. The results support the hypothesis; that semipermeable wound dressings augment barrier repair and skin quality by providing an optimized water vapor gradient during the wound healing process. The choice of wound dressing is discussed within the larger context of the design of vapor-permeable fabrics (smart materials) and the new fields of corneotherapy and comfort science.

Continuous measurement of core body temperature in preterm infants.

We tested a transcutaneous core temperature sensor using a method that relies on the principle of zero heat flow. We tested the hypothesis that transcutaneous and rectal temperatures would track within 0.3 degrees C of each other for >90% of the time. A thermistor was placed between the infant's abdomen or back and the incubator's or radiant warmer's mattress, or within the axilla, attached to the skin with a foam adhesive disk insulator. Thirty preterm infants were either placed on their abdomens or backs in a convective incubator or under a radiant warmer, and continuous transcutaneous and rectal temperatures were measured for 1 hour. There were no significant differences between abdominal and core temperatures or between axillary and core temperatures measured in double-walled convective incubators or in radiant warmers. The rectal-abdominal temperature difference was significantly less than the rectal-axillary difference (p < 0.02) in convective incubators, but not when the infant was placed prone under radiant warmers (p = 0.27). Transcutaneous thermometry is reliable for monitoring core body temperature as indicated by rectal temperature in stable preterm infants in a convective incubator.

Characterization of vernix caseosa: water content, morphology, and elemental analysis.

Recent studies have prompted interest in the use of epidermal barrier creams as protective biofilms for very low birthweight preterm infants. The key to understanding the role of epidermal barrier films is an elucidation of their interaction with water and a basic knowledge of their composition. In this study, we investigated the morphologic properties and elemental composition of the naturally occurring biofilm, vernix caseosa. This biofilm is typically lacking in preterm infants and its production coincides in utero with terminal differentiation of the epidermis and formation of the stratum corneum. Significantly, vernix (80.5+/-1.0% H2O) had a much higher water content than other barrier creams (Eucerin: 17.1+/-0.6%, Aquaphor: 0.33+/-0.03%, Ilex: 0.19+/-0.02%, petrolatum: 0.03+/-0.01%; all p<0.05). Phase contrast microscopy of vernix showed multiple cellular elements with nucleic "ghosts" embedded in a putative lipid matrix. Transmission electron microscopy revealed flattened structures approximately 1-2 microm in thickness with distinct cellular envelopes indicative of differentiated corneocytes. Compared with mature corneocytes in adult stratum corneum, vernix corneocytes appeared swollen, the density of the keratin filaments was less, and there was a relative lack of tonofilament orientation. Cryofractured specimens were examined by cryoscanning electron microscopy with subsequent elemental localization by X-ray beam analysis. The findings indicate the high water content of vernix is largely compartmentalized within fetal corneocytes. These results are consistent with the novel view of vernix as a "fluid phase" stratum corneum consisting of a hydrophobic lipid matrix with embedded fetal corneocytes possessing unique biomechanical and water-binding properties.

Adhesives and emollients in the preterm infant.

This chapter focuses on recent advances in preterm infant skin care related to skin adhesion and skin emolliency. Different types of adhesives and hydrating agents are reviewed. Clinical applications are best guided by understanding the biology of epidermal barrier development. The role of xeric stress in accelerating formation of the stratum corneum is discussed along with the effects of occlusive agents and emollients on wound healing and epidermal barrier repair. The principles of skin moisturization are introduced. The concept is advanced that programmatic changes in skin adhesion and water handling occur during the normal ontogeny of superficial biofilms (sebum, sweat, acid mantle).

Characterization of vernix caseosa as a natural biofilm: comparison to standard oil-based ointments.

The application of occlusive films and oil-in-oil ointments has been reported to improve epidermal barrier function in very low birthweight, preterm infants. Such infants have a structurally immature stratum corneum and lack a surface coating of vernix caseosa. In this study we examined the short-term effects of topical application of vernix caseosa to human skin and contrasted these effects with commonly used ointments and water-in-oil emulsions. Specifically, vernix, Eucerin(R), Aquaphor(R), and petrolatum were applied to the volar skin surface of adult volunteers. Surface electrical capacitance (SEC) and transepidermal water loss (TEWL) were measured as indices of surface hydration. Sorption-desorption profiles were performed to determine skin surface hydrophobicity. Particular attention was given to monitoring the acute (0-120 minutes) changes following vernix treatment in order to compare these effects with earlier reports on the rate of skin surface drying in newborn infants following birth. Immediately after vernix application there was an increase in the rate of water loss from the skin surface. Relative to control skin and skin treated with the ointments and water-in-oil emulsions, the application of vernix to freshly bathed human skin resulted in a unique profile of temporal change in baseline surface hydration, moisture accumulation, and water-holding capacity. These results demonstrate major differences between human vernix and standard oil-based topical ointments. The results provide a framework for discussing the various properties of topical barriers applied to the very low birthweight infant.