Neurodevelopmental outcomes of extremely low birth weight infants ventilated with continuous positive airway pressure vs. mechanical ventilation.

OBJECTIVE: To compare continuous positive airway pressure (CPAP) vs. traditional mechanical ventilation (MV) at 24 h of age as predictors of neurodevelopmental (ND) outcomes in extremely low birth weight (ELBW) infants at 18-22 months corrected gestational age (CGA). METHODS: Infants ≤1000 g birth weight born from January 2000 through December 2006 at two hospitals at the Cincinnati site of the National Institute of Child Health and Human Development Neonatal Research Network were evaluated comparing CPAP (n = 198) vs. MV (n = 109). Primary outcomes included the Bayley Score of Infant Development Version II (BSID-II), presence of deafness, blindness, cerebral palsy, bronchopulmonary dysplasia and death. RESULTS: Ventilatory groups were similar in gender, rates of preterm prolonged rupture of membranes, antepartum hemorrhage, use of antenatal antibiotics, steroids, and tocolytics. Infants receiving CPAP weighed more, were older, were more likely to be non-Caucasian and from a singleton pregnancy. Infants receiving CPAP had better BSID-II scores, and lower rates of BPD and death. CONCLUSIONS: After adjusting for acuity differences, ventilatory strategy at 24 h of age independently predicts long-term neurodevelopmental outcome in ELBW infants.

Acute treatment with kerosene damages the dermal barrier and alters the distribution of topically applied benzo(a)pyrene in mice.

The dermal route is important in many occupational exposures. Some materials may reduce the barrier function of the skin to enhance absorption and effect on internal organs. We have reported previously that kerosene cleaning following treatment with used engine oil increased DNA adduct levels in the lungs of mice compared with animals treated with used oil alone. To investigate what other physiological parameters might be affected by kerosene, we conducted in vitro and in vivo measurements of skin barrier function. We also topically applied (3)H-BAP(100 nM in 25 µL acetone) and washed half the mice with 25 µL kerosene 1 hr after carcinogen application. Groups of four mice were euthanized from 1 to 72 hr after treatment. Skin, lungs, and livers were harvested from each animal and stored separately. Kerosene application reduced the barrier function of the skin in vitro beyond the effect of the acetone vehicle and the vehicle plus BAP. In vivo studies indicated that kerosene treatment reduced the barrier function at 4 and 8 hr post application and that the barrier function recovered at 24 hr after a single treatment. The fraction of the radiolabel remaining in the skin of animals treated with (3)H-BAP and washed with kerosene was significantly less than those not washed, beginning at 24 hr (p< 0.05). Fractional distribution to the lungs and livers of these animals became significantly elevated at this time. Kerosene treatment compromises dermal barrier function and the ability of the skin to retain water, enhances carcinogen absorption, and alters organ distribution. This appears to contribute to the increase in BAP DNA adducts we reported earlier.

Epidermal barrier treatments based on vernix caseosa.

BACKGROUND/AIMS: Premature infants lack the vernix caseosa, have an incompetent stratum corneum (SC) barrier and are predisposed to infection. Use of topical agents to improve barrier function has had mixed outcomes. The aim was to determine the effect of vernix versus common barrier creams on the rate and quality of the epidermal barrier repair following controlled wounding. METHODS: Minor wounds were created with (1) laser ablation in the minipig and (2) tape stripping of mother's volar skin as a model for premature skin. Native vernix was applied to the mother's tape-stripped skin. Treatments were no occlusion (NO), vernix and a petrolatum-based cream (PBC) in the pig, and NO, vernix, PBC, an oil-in-water cream (OWC), a semipermeable film (SP) and full occlusion (FO) in adults. RESULTS: Outcomes for both trials were barrier recovery and skin hydration (moisture accumulation rate, MAT), initial hydration, erythema and dryness in adults. Vernix and PBC produced greater barrier repair than NO in the pig. SP produced greater recovery than NO and FO in adults. Vernix yielded greater recovery than FO and was similar to PBC, OWC and NO. Vernix had a directionally higher MAT than OWC and directionally higher initial hydration than NO. CONCLUSIONS: The findings suggest that vernix-based topical creams would be effective for the treatment of epidermal wounds and show promise to augment SC repair and maturation in infants.

Neonatal skin maturation--vernix caseosa and free amino acids.

Neonatal skin hydration decreases rapidly postnatally and then increases, indicating adaptive changes in stratum corneum water handling properties. Transition from high to low humidity at birth may initiate filaggrin proteolysis to free amino acids. Neonatal skin with vernix caseosa retained is more hydrated than skin with vernix removed. This study examines the potential roles of free amino acids and vernix in postnatal adaptation of infant stratum corneum in vivo. Specifically, the ontogeny of free amino acid generation in neonatal stratum corneum and the role of vernix caseosa in postnatal adaptation were examined using high performance liquid chromatography. Free amino acids were quantified for infant skin samples collected at (i) birth and 1 month and (ii) birth and 24 hours after vernix caseosa retention or removal and compared to neonatal foreskin, vernix caseosa, and adult stratum corneum using t-tests, analysis of variance, or univariate procedures. Free amino acids were extremely low at birth, significantly higher 1 month later but lower than in adults. Vernix caseosa retention led to significantly higher free amino acids 24 hours after birth compared to infants with vernix caseosa removed, and it paralleled the higher stratum corneum hydration of vernix caseosa-retained skin. Vernix caseosa contained free amino acids, with glutamic acid and histidine levels higher than in infants. Free amino acids in vernix caseosa-retained skin appear to originate from vernix caseosa. Free amino acids were lower in neonatal foreskin than adult forearm stratum corneum. Arginine was higher than citrulline at birth, but levels were comparable in older infants. The free amino acid increase at 1 month may be initiated by the humidity transition at birth and supports results in animals. The findings have implications for infant skin care practices.

Amputee skin condition: occlusion, stratum corneum hydration and free amino acid levels.

Patients with a prosthetic limb report negative skin effects, including irritation, rash and chafing, which can lead to infection, discomfort and reduced wear time to significantly impact normal activities. The aims were to examine the epidermal integrity (transepidermal water loss, TEWL), stratum corneum (SC) hydration [moisture accumulation rate (MAT)], friction and biomechanical properties in active below the knee amputees and to determine the effects of an inert sock liner on skin condition. The liner reduced hydration, TEWL and friction and increased elasticity versus the amputee's conventional skin care methods. Residual limb TEWL was increased and MAT was reduced versus the contralateral normal skin. In a second study, we hypothesized that complete occlusion would decrease free amino acids (FAA) and quantified them by high performance liquid chromatography in an adult volar forearm model. Occlusion with a water vapor impermeable wet dressing led to increased TEWL, erythema and dryness and reduced MAT versus normal skin, comparable to the results in the amputees. The FAA levels were significantly reduced for the occluded sites. The results suggest that residual limb occlusion in amputees may block the formation of FAA in the upper SC. Therapies based on replacement of water binding FAAs, may alleviate the consequences of long-term occlusion.

Influence of tumour necrosis factor-α polymorphism-308 and atopy on irritant contact dermatitis in healthcare workers.

BACKGROUND: Chronic irritant hand dermatitis is an issue for healthcare workers and may negatively impact infection control. OBJECTIVES: We examined the effects of a G to A transition at position -308 on the tumour necrosis factor-α (TNF-α) gene on chronically damaged skin of healthcare workers during exposure and recovery from repetitive hand hygiene, after intensive treatment, and on the irritant response in normal skin. PATIENTS/MATERIALS/METHODS: In 68 healthcare workers with irritant hand dermatitis, we genotyped TNF-α-308 and measured the epidermal response via quantitative digital imaging, erythema, dryness, and barrier integrity. RESULTS: Excess hand erythema decreased with hand hygiene exposure and increased during time off for AA/GA genotypes, but had opposite effects for GG. AA/GA had smaller reductions in dryness with lotion treatment and larger reductions in excess erythema than GG. The atopic diathesis and heightened neurosensory irritation resulting from water and lactic acid significantly influenced the responses. Repeated exposure to water and sodium lauryl sulfate (0.05, 0.1%) produced higher erythema in normal skin for AA/GA than for GG. CONCLUSIONS: This study provides evidence that the TNF-α polymorphism at -308 and an atopic history impact the severity of irritation and recovery from exposure and response to treatment for common hand skin products in both chronic irritant hand dermatitis and normal skin.

Biomarkers of epidermal innate immunity in premature and full-term infants.

Epidermal innate immunity is a complex process involving a balance of pro- and anti-inflammatory cytokines, structural proteins, and specific antigen presenting cells occurring against a background of neuroendocrine modulators such as cortisol. In this study, a multiplex array system was used to simultaneously determine multiple molecular factors critical for development of epidermal innate immune function from the skin surface of premature and term infants, healthy adults, and vernix caseosa. Samples were analyzed for Keratin 1,10,11, Keratin 6, involucrin, albumin, fibronectin and cortisol, and cytokines IL-1, TNFalpha, IL-6, IL-8, MCP1, IP10, IFNgamma, and IL-1 receptor antagonist. Keratin 1,10,11 was decreased and involucrin was increased in infants versus adults. All infants had elevated IL1alpha and reduced TNFalpha versus adults. IL-6, IL-8, and MCP1 were significantly increased in premature versus term infants and adults. Skin surface cortisol and albumin were significantly elevated in premature infants. The biomarker profile in premature infants was unique with differences in structural proteins, albumin, and cytokines IL-6, IL-1beta, IL-8, and MCP1. The higher infant IL1alpha may be associated with skin barrier maturation. The significant elevations in skin surface cortisol for preterm infants may reflect a neuroendocrine response to the stress of premature birth.

Improved barrier function observed in cultured skin substitutes developed under anchored conditions.

BACKGROUND/PURPOSE: The current method of producing cultured skin substitutes (CSS) is focused on providing treatments for severe skin wounds/burns. We have developed a modified growth method to make them more suitable for in vitro product-testing/toxicity-testing purposes. METHOD: CSS grown in Petri dishes were either transferred to Franz diffusion cells on day 5 (modified method) or left in the Petri dish (standard method) and maintained in these environments for the remainder of the growth phase. Mitochondrial metabolism (MTT assay) was measured on days 5, 10 and 14 and histology was studied on days 5, 10 and 14. Barrier function for all tissues was evaluated by transferring them to Franz cells (standard method) and measuring transepidermal water loss (TEWL), 3H2O penetration and 14C-niacinamide permeability on days 7, 14 and 21. RESULTS: CSS grown by the standard and modified methods showed comparable cell viability and tissue morphology. Barrier function, however, was markedly improved in CSS grown by the modified method. The average improvement at days 7 and 14 was 1.3-fold for TEWL, 2.1-fold for 3H2O penetration and 6.4-fold for 14C-niacinamide permeability. The barrier function of CSS grown by the modified method was still significantly lower than that of human cadaver skin tested by the same methods. CONCLUSIONS: CSS developed using the anchored multi-cell system showed similar cell viability and morphology and improved barrier function compared with CSS produced by the standard Petri dish method, thereby improving its potential as an in vitro skin permeability and toxicity model.

The universe of developmental care: a new conceptual model for application in the neonatal intensive care unit.

Developmental care for high-risk infants is practiced in most neonatal units around the world. Despite its wide acceptance, inconsistency in its definition and application has resulted in criticism regarding its scientific merit. The universe of developmental care model proposed in this article is the first major reformulation of neonatal developmental care theory since Als' synactive theory. Neither the developing brain nor the environment exists in isolation, and therefore are dependent on each other for all caregiving activities. Central to this model is the concept of a shared surface, manifested most obviously by the skin that forms the critical link between the body/organism and environment and becomes the focal point for human interactions. The components of the model and its theoretical underpinnings, its practical application and direction for future clinical practice, education, and research are presented.

Host defense proteins on the surface of neonatal skin: implications for innate immunity.

OBJECTIVES: To compare the spectrum, concentration, and activity of host defense proteins (HDPs) on the skin surface of newborns and adults, to assess variation in HDP concentrations in different anatomic regions in newborns, and to examine alteration in HDP concentrations with care practices. STUDY DESIGN: Proteins recovered from tape discs applied to stratum corneum of 25 term newborns (forehead and posterior trunk) and 20 adults (forehead) were analyzed by Western analysis for 5 HDPs and for muramidase activity. Protein concentrations were compared in samples obtained after delivery, after the first bath, and at 24 hours of age. RESULTS: Total protein was 2.8-fold higher in adults compared with newborns. Lysozyme and lactoferrin were detected in all samples. In contrast to total protein, lysozyme concentrations and muramidase activity were 5-fold higher in newborns relative to adults and were not altered after bathing. Lysozyme concentrations were significantly higher over the trunk compared with the forehead in newborns. CONCLUSIONS: The newborn skin surface is replete with prototypical HDPs, lysozyme, and lactoferrin. Bathing does not significantly diminish concentrations. These factors are likely to contribute importantly to the newborn infants' defense against invasive bacterial infections.

Equilibrium water content in native vernix and its cellular component.

Vernix caseosa is a naturally occurring substance coating the skin of newborn humans. Structurally, vernix contains fetal corneocytes embedded in a hydrophobic lipid matrix. Despite a relatively high water content approximating 80.7%, vernix exhibits slow water release. In this study, we quantified and contrasted the water release and uptake properties of native vernix and its isolated cellular component over the full range of water activity. Theoretical water sorption models (D'Arcy-Watt, and Frenkel-Halsey-Hill (FHH), and Guggenheim-Anderson-de Boer (GAB)) were fit to the vernix water sorption data. Each of the theoretical models provided a satisfactory description of the equilibrium water content of vernix over the water activity range 0.15-1.0. Vernix corneocytes without the surrounding lipid matrix exhibited markedly increased equilibrium water binding at water activities greater than 0.62 compared to native vernix. Resorption experiments showed full recovery of water content in both native vernix and isolated corneocytes supporting a structured internal domain. These results provide the first quantitative characterization of the water handling properties of native vernix and its cellular component. Such information may prove useful in the design of alternative skin care moisturizing formulations.

Amplitude-integrated EEG is useful in predicting neurodevelopmental outcome in full-term infants with hypoxic-ischemic encephalopathy: a meta-analysis.

Hypoxic ischemic encephalopathy is a common cause of neurological complications resulting in chronic handicapping conditions, such as cerebral palsy. Amplitude-integrated electroencephalography (EEG) has been used in many European countries for more than a decade in the evaluation of infants with hypoxic ischemic encephalopathy but has not been widely used in the United States. The objective of this study was to evaluate the evidence supporting use of amplitude-integrated EEG as a quantitative predictor of neurodevelopmental outcome in full-term infants with hypoxic ischemic encephalopathy. To assess efficacy, the authors performed a meta-analysis of the literature evaluating the use of the amplitude-integrated EEG or cerebral function monitor in full-term infants with hypoxic ischemic encephalopathy and their neurodevelopmental outcome. A total of 8 studies were eligible for the primary meta-analysis. There was an overall sensitivity of 91% (95% CI 87-95) and a negative likelihood ratio of 0.09 (95% CI .06-.15) for amplitude-integrated EEG tracings to accurately predict poor outcome. Amplitude-integrated EEG is a valuable bedside tool for predicting long-term neurodevelopmental outcome in term infants with hypoxic ischemic encephalopathy. This information is useful in structuring communication and care plans for physicians and parents. Early assessment techniques such as amplitude-integrated EEG provide objective means for determining inclusion in clinical studies evaluating therapies for hypoxic ischemic encephalopathy and for predicting which patients are most likely to respond to treatment.

Effect of vernix caseosa on the penetration of chymotryptic enzyme: potential role in epidermal barrier development.

The fetal epidermal barrier undergoes rapid development during late gestation despite conditions injurious to the skin postnatally, i.e. prolonged exposure to water (urine) and noxious substances such as pancreatic chymotrypsin. Nevertheless, at birth, term newborns have a superb epidermal barrier. Concomitant with formation of the stratum corneum in utero, vernix caseosa forms a natural multifunctional cream separating the skin surface from the amniotic fluid with possible unique barrier properties. Therefore, we investigated the effect of native vernix, synthetic vernix, and Desitin on penetration of chymotrypsin, a proteolytic enzyme present in both developing epidermis and meconium. Alpha-chymotrypsin penetration through test materials was conducted in vitro using a modified Franz diffusion cell. The presence of alpha-chymotrypsin in vernix and a possible inhibitory effect of vernix on alpha-chymotrypsin activity were investigated. Vernix films significantly impeded chymotrypsin penetration compared with controls during 24-h exposure experiments. Alpha-chymotryptic activity in vernix was undetectable, and vernix showed no endogenous inhibition of such activity. Both synthetic vernix and Desitin significantly impeded alpha-chymotrypsin penetration compared with controls during 9-h exposure experiments. With respect to the developing epidermal barrier, these results are consistent with the hypothesis that vernix films retain endogenous (epidermal) chymotrypsin while preventing exposure to exogenous (pancreatic) chymotrypsin.

New insights into ultrastructure, lipid composition and organization of vernix caseosa.

The upper layer of the epidermis, the stratum corneum (SC), is very important for skin barrier function. During the last trimester of gestation, the SC of the fetus is protected by a cheesy, white biofilm called vernix caseosa (VC). VC consists of water-containing corneocytes embedded in a lipid matrix and the basic structure shows certain similarities with the SC. This study aimed to characterize VC, with the main focus on an integral analysis of free and (to the corneocytes) bound lipids, on the lipid organization, and on ultrastructure. Free lipids of VC show a wide distribution in polarity; nonpolar lipids such as sterol esters and triglycerides predominate, having a chain length of up to 32 carbon atoms. The profile of fatty acids, omega-hydroxyacids and omega-hydroxyceramides - representing the bound lipids of VC - shows high similarity to that of SC. Morphological studies revealed the presence of highly hydrated corneocytes embedded in lipids, the latter being occasionally accumulated as lipid pools. Freeze fracture electron microscopy showed smooth surfaces of corneocytes and a heterogeneous appearance of intercellular lipids. The results suggest a lower degree of ordering of VC lipids as compared to the SC. A small-angle X-ray diffraction study showed similar results.

The human stratum corneum as extended, covalently cross-linked biopolymer: mathematics, molecules, and medicine.

A novel mathematical and molecular hypothesis is proposed to account for the peculiar organization of human epidermis. Mathematically, the organization of the interfollicular epidermis is hypothesized to be a tetratomic identity manifesting a gravitational logic in the arrangement of its functional compartments. The squares of the natural numbers; i.e., 1, 4, 9, and 16 are taken, on empirical grounds, to correspond to the number of cell layers in the respective epidermal strata (germinativum, spinosum, granulosum, and corneum). The outer two strata, overlying the Langerhans cells, constitute the 'living' and 'dead' components of the traditional 'epidermal barrier'. Together, these two strata illustrate in their union of 9 + 16 = 25 cells, a way of conceiving the skin surface (the body-environment identity) as both closure and contact. The organization of human epidermis into functional units based on phi, the golden section ratio, builds upon this gravitational logic. Finally, the fact that the extensively cross-linked proteolipid envelope of the cornified epidermal cell is a single multi-gene molecule is deemed scientifically incontrovertible. The molecular hypothesis in need of validation and verification is whether the corneodesmosomal 'rivets' linking one corneocyte to another are covalently bonded structures. If so, the cornified scaffolding of the stratum corneum constitutes a highly organized, extended, multi-gene, polymer molecule strategically located precisely at the shared surface of the body and environment. This hypothesis places the differentiated structure of the epidermis, an ectodermal derivative like the brain, front and center in the translation of molecular biology to clinical bedside care.

Vernix caseosa in neonatal adaptation.

OBJECTIVES: To characterize vernix caseosa in newborn infants with respect to factors that influence vernix distribution on the skin surface, vernix effects on thermal stability, skin hydration, acid mantle development, and vernix antioxidant properties. STUDY DESIGN: Vernix distribution was determined for 430 infants. Thermal stability was assessed in parallel groups following vernix retention (n=66) and removal (n=64). The effects of vernix retention on skin hydration, pH, erythema, and dryness/scaling were determined. Samples were analyzed for vitamin E before and after UV exposure. RESULTS: Vernix distribution depended upon gestational age, delivery mode, gender, race, and meconium exposure. Retention had no effect on axillary temperatures. Skin hydration was significantly higher for vernix-retained skin. Skin pH and erythema were significantly lower with retention. Vitamin E levels were decreased by ultraviolet radiation. CONCLUSIONS: Vernix is a naturally occurring barrier cream with multiple salubrious effects, which support its retention on the skin surface at birth.

Host defense proteins in vernix caseosa and amniotic fluid.

OBJECTIVE: This study was undertaken to define the spectrum, activity, and spatial distribution of antimicrobial peptides in vernix caseosa and amniotic fluid in the absence of clinical chorioamnionitis. STUDY DESIGN: Characterization of innate immune proteins in vernix and amniotic fluid obtained from pregnancies with gestational ages greater than 37 weeks by Western analysis, immunohistochemistry, and antimicrobial growth inhibition assay. RESULTS: Lysozyme, lactoferrin, human neutrophil peptides 1-3, and secretory leukocyte protease inhibitor were identified by Western analysis in vernix suspensions (n = 25) and amniotic fluid samples (n = 10). Three other important antimicrobial proteins, human beta defensin-2, lactoperoxidase, and LL-37 were not detected. Amniotic fluid and soluble extracts of vernix exhibited muramidase (lysozyme) activity, and there was selective efficacy in inhibiting growth of common perinatal pathogens. Antimicrobial peptides were concentrated in discrete, organized, acellular "granules" embedded in the vernix lipid matrix. CONCLUSION: In the absence of chorioamnionitis, vernix and amniotic fluid contain an organized pool of antimicrobial peptides with a defined spectrum of bioactivity against common bacterial and fungal pathogens.

Evaluation of a low-dose lidocaine iontophoresis system for topical anesthesia in adults and children: a randomized, controlled trial.

BACKGROUND: Commonly used classes of topical anesthetics require 30 to 60 minutes to provide effective anesthesia. A new low-dose lidocaine iontophoresis system (LDLIS) may provide topical anesthesia in 10 minutes at a lower dose than previous systems, thereby limiting adverse events. METHODS: This was a prospective, randomized, multicenter, double-blind, placebo-controlled, clinical trial. Adults and children aged 5 to 17 years (inclusive) received a 10-minute ionntophoretic treatment with either lidocaine or a saline placebo before venipuncture or venous cannulation. Intensity of pain associated with venipuncture or venous cannulation was assessed using either a 10-cm Visual Analog Scale (VAS) for adults and children aged 12 to 17 years or the Facial Affective Scale (FAS) for all children enrolled. RESULTS: Five hundred forty-eight patients (276 adults, 272 children) participated. Mean (SD) VAS pain scores were lower in adults who received iontophoresis with lidocaine rather than with placebo (0.77 [1.49] vs 2.52 [2.30], P < 0.001) and in children aged 12 to 17 years (1.50 [1.87] vs 2.58 [2.26], P = 0.001). FAS pain scores were lower among children who received iontophoresis with lidocaine rather than with placebo (0.36 [0.26] vs 0.51 [0.27], P < 0.001). Similar results were found for children stratified by age group (5-7 years: 0.40 [0.30] vs 0.60 [0.31], P = 0.011; 8-11 years: 0.35 [0.27] vs 0.48 [0.27], P = 0.021; 12-17 years: 0.33 [0.21] vs 0.48 [0.24], P = 0.001). Mean (SD) parental ratings of pain on the FAS for children aged 5 to 11 years were also lower for the lidocaine group (0.45 [0.28] vs 0.55 [0.25], P = 0.018). Adverse events were similar between groups and included skin erythema and edema. One patient in the study experienced a partial-thickness burn. CONCLUSION: In this study of adults and children, the LDLIS provided effective topical anesthesia for venipuncture and venous cannulation within 10 minutes.

The organization of human epidermis: functional epidermal units and phi proportionality.

The concept that mammalian epidermis is structurally organized into functional epidermal units has been proposed on the basis of stratum corneum (SC) architecture, proliferation kinetics, melanocyte:keratinocyte ratios (1:36), and, more recently, Langerhans cell: epidermal cell ratios (1:53). This article examines the concept of functional epidermal units in human skin in which the maintenance of phi (1.618034) proportionality provides a central organizing principle. The following empirical measurements were used: 75,346 nucleated epidermal cells per mm2, 1394 Langerhans cells per mm2, 1999 melanocytes per mm2, 16 (SC) layers, 900-microm2 corneocyte surface area, 17,778 corneocytes per mm2, 14-d (SC) turnover time, and 93,124 per mm2 total epidermal cells. Given these empirical data: (1) the number of corneocytes is a mean proportional between the sum of the Langerhans cell + melanocyte populations and the number of epidermal cells, 3393/17,778-17,778/93,124; (2) the ratio of nucleated epidermal cells over corneocytes is phi proportional, 75,346/17,778 approximately phi3; (3) assuming similar 14-d turnover times for the (SC) and Malpighian epidermis, the number of corneocytes results from subtraction of a cellular fraction equal to approximately 2/phi2 x the number of living cells, 75,436 - (2/phi2 x 75,346) approximately 17,778; and (4) if total epidermal turnover time equals (SC) turnover time x the ratio of living/dead cells, then compartmental turnover times are unequal (14 d for (SC) to 45.3 d for nucleated epidermis approximately 1/2phi) and cellular replacement rates are 52.9 corneocytes/69.3 keratinocytes per mm2 per h approximately 2/phi2. These empirically derived equivalences provide logicomathematical support for the presence of functional epidermal units in human skin. Validation of a phi proportional unit architecture in human epidermis will be important for tissue engineering of skin and the design of instruments for skin measurement.

Effect of soaking and natural moisturizing factor on stratum corneum water-handling properties.

Stratum corneum (SC) hydration is partially regulated by water-soluble molecules, natural moisturizing factor (NMF) that is associated with the corneocytes. Routine water exposure, e.g., bathing, may deplete NMF and alter the SC water-handling properties. We determined the effects of bathing and solvent extraction on the volar forearm skin of eleven healthy volunteers. Acetone/ether (A/E) was used to remove surface and upper SC lipids. Adjacent sites were soaked for ten minutes or treated with the A/E-plus-soak combination. Subsequently, an NMF formulation was applied to the treated sites, and transepidermal water loss (TEWL), hydration, and moisture accumulation rate (MAT) were measured. A/E extraction increased TEWL, but did not effect MAT. Soaking produced a short-term increase in TEWL, followed by a decrease, and substantially reduced MAT, an effect that was maintained for five hours. NMF application significantly decreased TEWL and significantly increased MAT for all sites. The replacement experiment suggests that the MAT reduction occurred as a result of extraction of hygroscopic NMF components. The effects of soaking and NMF application are more readily detected by the MAT technique, whereas TEWL is more sensitive to A/E extraction. The results support the use of multiple assessments of barrier function and raise questions about the effects of cumulative repeated water exposure on SC function.