The Skin Barrier and Moisturization: Function, Disruption, and Mechanisms of Repair.

BACKGROUND: The anatomic layers of the skin are well-defined, and a functional model of the skin barrier has recently been described. Barrier disruption plays a key role in several skin conditions, and moisturization is recommended as an initial treatment in conditions such as atopic dermatitis. This review aimed to analyze the skin barrier in the context of the function model, with a focus on the mechanisms by which moisturizers support each of the functional layers of the skin barrier to promote homeostasis and repair. SUMMARY: The skin barrier is comprised of four interdependent layers - physical, chemical, microbiologic, and immunologic - which maintain barrier structure and function. Moisturizers target disruption affecting each of these four layers through several mechanisms and were shown to improve transepidermal water loss in several studies. Occlusives, humectants, and emollients occlude the surface of the stratum corneum (SC), draw water from the dermis into the epidermis, and assimilate into the SC, respectively, in order to strengthen the physical skin barrier. Acidic moisturizers bolster the chemical skin barrier by supporting optimal enzymatic function, increasing ceramide production, and facilitating ideal conditions for commensal microorganisms. Regular moisturization may strengthen the immunologic skin barrier by reducing permeability and subsequent allergen penetration and sensitization. KEY MESSAGES: The physical, chemical, microbiologic, and immunologic layers of the skin barrier are each uniquely impacted in states of skin barrier disruption. Moisturizers target each of the layers of the skin barrier to maintain homeostasis and facilitate repair.

The Effect of Sun Tan Lotion on Skin by Using Skin TEWL and Skin Water Content Measurements.

Stratum corneum (SC) is the outermost skin layer. SC hydration is important for its cosmetic properties and barrier function. SC trans-epidermal water loss (TEWL) measurements and skin water content measurements are two key indexes used for SC characterisation. The instrument stability and accuracy are vitally important when measuring small changes. In this paper, we present our latest study on the effect of sun tan lotion on skin by using skin TEWL and skin water content measurements. We developed techniques to improve the measurement stability and to visualise small changes, as well as developed machine learning algorithms for processing the skin capacitive images. The overall results show that TEWL and skin water content measurements are capable of measuring the subtle changes of skin conditions due to the application of sun tan lotions. The results show that the TEWL values decreased after the sun tan lotion application. The sun tan lotion with SPF 20 had the lowest decrease, whilst the sun tan lotion with SPF 50+ had the highest decrease. The results also show that the skin water content increased after the sun tan lotion application, with SPF 20 having the highest increase, whilst SPF 50+ had the lowest increase.

Optimization, kinetic, and scaling-up of solvent-free lipase-catalyzed synthesis of ethylene glycol oleate emollient ester.

The use of enzymatic catalysts is an alternative to chemical catalysts as they can help to obtain products with less environmental impact, considered sustainable within the concept of green chemistry. The optimization, kinetic, lipase reuse, and scale-up of enzymatic production of ethylene glycol oleate in the batch mode were carried out using the NS 88011 lipase in a solvent-free system. For the optimization step, a 23 Central Composite Design was used and the optimized condition for the ethylene glycol oleate production, with conversions above 99%, was at 70 °C, 600 rpm, substrates molar ratio of 1:2, 1 wt% of NS 88011 in 32 H of reaction. Kinetic tests were also carried out with different amounts of enzyme, and it showed that by decreasing the amount of the enzyme, the conversion also decreases. The lipase reuse showed good conversions until the second cycle of use, after which it had a progressive reduction reaching 83% in the fourth cycle of use. The scale-up (ninefold increase) showed promising results, with conversion above 99%, achieving conversions similar to small-scale reactions. Therefore, this work proposed an environmentally safe route to produce an emollient ester using a low-cost biocatalyst in a solvent-free system.

Dermatology Part 2: Ichthyoses and Psoriasis.

Acute and chronic inflammatory skin diseases are frequent in childhood and may be hereditary or acquired. In this context, ichthyosis is rather a symptom than a defined disease as scaling is accompanying a number of disorders and is mostly consequence of a disrupted skin barrier. Ichthyosis is the basic pathogenic trait of atopic dermatitis but on the other side describes a group of rare hereditary diseases. These may only affect the skin or comprise several internal symptoms as well. Psoriasis is another scaling inflammatory skin disease with classical sharply demarcated erythematosquamous plaques and with a distinct immunogenetic background. It comprises several clinical subsets, some of which are characteristic for children and demanding in both diagnostics and therapy. Comorbid diseases point towards a systemic inflammatory response and require ample, often systemic treatment. Both ichthyosis and psoriasis may be topically treated including emollients with and without humectants as well as active agents like corticosteroids, vitamin D derivatives, and calcineurin inhibitors. In moderate to severe diseases, systemic treatment should be applied using methotrexate, ciclosporin, fumarates, or biologics. Their use should be critically discussed yet if necessary and indicated be applied to avoid chronic physical and psychological damage to the affected children.

Stability Assessment of Topical Amitriptyline Extemporaneously Compounded with Lipoderm Base, PLO Gel Mediflo 30, and Emollient Cream.

Extemporaneous topical compounds for neuropathic pain offers an alternative or adjunct approach to existing therapies for patients. Assigning evidence-based beyond-use dating prior to dispensing topical medications is a legal requirement by pharmacy governing bodies. The purpose of this study was to utilize a validated stability-indicating high-performance liquid chromatography assay to determine beyond-use dating of topical amitriptyline in three different bases (Lipoderm Base, PLO Gel Mediflo 30, Emollient Cream) at three different temperatures [room temperature (25°C), refrigeration (4°C), and high temperature (40°C)]. Amitriptyline was stable after 90 days at room temperature in both Lipoderm Base and PLO Gel Mediflo 30. However, it was not stable at 40°C in Emollient Cream, irrespective of storage conditions.

Moisturizers versus Current and Next-Generation Barrier Repair Therapy for the Management of Atopic Dermatitis.

We compare here the principal characteristics of over-the-counter moisturizers with physiologic lipid-based barrier repair therapy. Moisturizers are standard ancillary therapy for anti-inflammatory skin disorders, like atopic dermatitis (AD), and can attenuate the emergence of AD, the initial step in the "atopic march." But not all moisturizers are beneficial; some can make skin function worse, and can even induce inflammation, possibly accounting for the frequent occurrence of "sensitive skin" in women. In contrast, physiologic lipid-based barrier repair therapy, if comprised of the 3 key stratum corneum lipids, in sufficient quantities and at an appropriate molar ratio, can correct the barrier abnormality and reduce inflammation in AD, and perhaps in other inflammatory dermatoses.

The Effect of an Emollient Containing Urea, Ceramide NP, and Lactate on Skin Barrier Structure and Function in Older People with Dry Skin.

Xerosis affects up to 75% of older people and develops as a result of a skin barrier defect. Emollients are widely used to treat xerosis; however, there is limited understanding of the differences between them and their effects on the skin barrier in older people. This study aimed to compare the effect of a commercially available emollient containing 5% urea, ceramide NP and lactate (test emollient) to an alternative emollient without these additives (control emollient) on the properties of the skin barrier in older people. Two cohorts of 21 volunteers aged >60 years with dry skin were recruited. The first applied the test emollient to one forearm and no treatment to the other for 28 days. The second compared the test emollient to the control emollient observing the same parameters. Effects on the skin barrier were determined by measuring skin barrier function, hydration, skin surface pH and by analysing Fourier transform infrared spectra before and after treatment. A third cohort of 6 young adults was recruited to investigate the effect of a single treatment with the test emollient on the molecular structure of the skin barrier at greater depths by employing the tape-stripping technique. The test emollient hydrated the skin to a significantly greater extent and for a longer period of time compared to the control emollient, an effect associated with a significant elevation of carboxylate groups (a marker of natural moisturizing factor content) within the stratum corneum. Furthermore, the test emollient imparted additional benefits to the structure and function of the skin barrier not exhibited by the control emollient. In conclusion, the test emollient addressed the pathological features of xerotic aged skin, supporting its use as first-line therapy for xerotic skin conditions in this population.

Reacción cutánea mano-pie por regorafenib / Hand-Foot Skin Reaction to Regorafenib

No disponible

Hydrogel-based ultra-moisturizing cream formulation for skin hydration and enhanced dermal drug delivery.

To develop an external vehicle for skin hydration and enhanced dermal drug delivery, a hydrogel-based ultra-moisturizing cream (HUMC) was successfully formulated with carbopol 934P, urea, Tinocare GL, grape seed oil, and other excipients. The HUMC showed plastic flow behavior due to a gel structure with a cream base. Different types of drug-free vehicles such as a hydrogel, conventional cream (CC), and three HUMCs were prepared and subjected to an in vivo skin hydration test on a hairless mouse using a corneometer. Hydration effect (∆AU) was in the order of HUMC2>HUMC1 ≥ CC>HUMC3>hydrogel. Using nile red (NR) and 5-carboxyfluorescein (5-CF) as lipophilic and hydrophilic fluorescent probes, respectively, in vitro skin permeation and accumulation studies were conducted using Franz diffusion cells. The values of steady-state flux (Jss, ng/h/cm(2)) were obtained: 74.8 (CC), 145.6 (HUMC1), and 161.9 (HUMC2) for NR delivery; 6.8 (CC), 8.3 (HUMC1), and 10.9 (HUMC2) for 5-CF delivery. The amounts retained in the skin at 12 h (Qr, ng/cm(2)) were determined: 86.4 (CC) and 102.0 (HUMC2) for NR; and 70.1 (CC) and 195.6 (HUMC2) for 5-CF. Confocal microscopy was used to visualize the distribution of the fluorescent probes. NR tended to be localized into the deeper part of the skin with adipose tissue whereas 5-CF localized in the upper layer of the skin. Thus we propose that HUMC2 is an efficacious vehicle for skin hydration and enhances dermal delivery of lipophilic and hydrophilic drugs.

Transepidermal water loss (TEWL) and corneometry with hydrogel vehicle in the treatment of atopic dermatitis: a randomized, investigator-blind pilot study.

Disruption of the epidermal barrier, as indicated by a reduction in skin hydration and an increase in transepidermal water loss (TEWL) is a feature of atopic dermatitis (AD). Novel formulations of dermatologic therapies may enhance patient satisfaction and adherence and may possibly preserve and enhance epidermal barrier function. A single-center, investigator-blinded, randomized, split-body exploratory study was undertaken to assess the hydrating and barrier preserving effects of a water-based hydrogel vehicle. Subjects (n=20) with mild to moderate disease at baseline applied hydrogel vehicle or a moisturizing lotion (Eucerin Lotion®, Beiersdorf, Inc.) in a split-body fashion for two weeks. Corneometry and TEWL measurements were taken at baseline and week 2. Hydrogel vehicle produced a statistically significant improvement in skin hydration from baseline, as compared to a moisturizing lotion control. Hydrogel produced no statistically significant change in TEWL, while comparator lotion increased TEWL. Data from this pilot study indicate that the water-based hydrogel vehicle improves skin hydration and does not further impair epidermal barrier function, suggesting that it is an appropriate vehicle choice for patients with mild-to-moderate atopic dermatitis.

Two randomized, controlled, comparative studies of the stratum corneum integrity benefits of two cosmetic niacinamide/glycerin body moisturizers vs. conventional body moisturizers.

BACKGROUND AND OBJECTIVE: Despite numerous body moisturizers being available, cosmetic xerosis continues to be a leading skin problem for consumers. We performed two 35-day studies to evaluate the ability of a variety of body moisturizers containing various levels of oils/lipids, humectants, as well as other ingredients (e.g., niacinamide) to improve stratum corneum integrity. METHODS: 63 and 58 female subjects were enrolled and randomized in an incomplete block design to six of nine products (eight moisturizers or no treatment control) in studies 1 and 2, respectively. The primary endpoints included visual dryness by a qualified skin grader, skin hydration as measured by Corneometer, and barrier integrity as measured by transepidermal water loss (TEWL). The primary comparisons for the two niacinamide/glycerin moisturizers were to the other six moisturizers and to the no treatment control for each endpoint. RESULTS: The two niacinamide/glycerin moisturizers demonstrated an overall better solution towards rapid and prolonged improvement of cosmetic xerosis due to functional improvement of stratum corneum barrier function compared to no treatment and the other moisturizers tested. CONCLUSIONS: These studies establish the benefit of including niacinamide in a body moisturizer to improve the integrity of the stratum corneum and thus reduce cosmetic xerosis over time.

A controlled trial of objective measures of sunscreen and moisturizing lotion.

Taking an alcohol swab of a person's forearm and analyzing it using a spectrophotometer has been shown to be a reliable method for detecting the presence of sunscreen. The aims of this study were to determine if moisturizing lotions or other non-sunscreen products influence the absorbance readings from skin swabs in a controlled setting, and to establish the cutoff point in determining the presence or absence of sunscreen using a crystal cuvette instead of a plastic one. In a controlled trial of 30 volunteer office workers, absorbance readings from two popular brands of sunscreen with sun-protection factors (SPF) of 30 and 45 were compared with absorbance readings from two different moisturizing lotions, one with an SPF of 15 and another with no stated SPF. Moisturizers with SPF 15 tested positive for sunscreen, with absorbance readings (mean, 3.77; min, 3.30) comparable to sunblock with SPF 30 or 45 (mean, 3.51; min, 2.02). Moisturizers with no stated SPF factor tested negative for the presence of sunscreen, with extremely low absorbance readings (mean, 0.06; max, 0.19) similar to control readings. The skin swabbing technique remains a valid and useful method for detecting the presence of sunscreen and does not result in false positives when moisturizers with no stated SPF are present. Using a conservative cutoff point of 0.30 with a crystal cuvette reduces any chance of false-positive readings and remains robust when sunscreen of SPF 15 or higher is present.

Glycerol and the skin: holistic approach to its origin and functions.

Glycerol is a trihydroxy alcohol that has been included for many years in topical dermatological preparations. In addition, endogenous glycerol plays a role in skin hydration, cutaneous elasticity and epidermal barrier repair. The aquaporin-3 transport channel and lipid metabolism in the pilosebaceous unit have been evidenced as potential pathways for endogenous delivery of glycerol and for its metabolism in the skin. Multiple effects of glycerol on the skin have been reported. The diverse actions of the polyol glycerol on the epidermis include improvement of stratum corneum hydration, skin barrier function and skin mechanical properties, inhibition of the stratum corneum lipid phase transition, protection against irritating stimuli, enhancement of desmosomal degradation, and acceleration of wound-healing processes. Even an antimicrobial effect has been demonstrated. Topical application of glycerol-containing products improves skin properties in diseases characterized by xerosis and impaired epidermal barrier function, such as atopic dermatitis. The increase of epidermal hydration by glycerol is critical in skin conditions aggravated by dry and cold environmental conditions, e.g. winter xerosis. This paper provides a review on effects of glycerol on the skin, the mechanisms of its action, and the potential applications of glycerol in dermatology.

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.

Cosmeceutical properties of levan produced by Zymomonas mobilis.

Levan, a polysaccharide that can be produced by both plants and microorganisms, is a sugar polymer composed of fructose, with beta-2,6 linkages. Here, we have attempted to assess the possible use of levan produced by Zymomonas mobilis as a cosmeceutical ingredient. In service of this goal, we assessed a host of levan's properties, including its moisturizing effects, cell cytotoxicity, cell proliferation effects, and anti-inflammation effects. Levan exhibited a moisturizing effect that was almost exactly the same as that evidenced by hyaluronic acid, as well as a similar cell proliferation effect in human fibroblast and keratinocyte cell lines. Moreover, in our cell proliferation test, which was conducted using bio-artificial skin constructed via 3-dimensional (3-D) culture after the induction of primary skin inflammation with 0.05% sodium lauryl sulfate (SLS), cell viability in the presence of levan (0.01 mg/ml, 0.05 mg/ml) was determined to be higher than cell viability in the absence of levan. In our anti-inflammation test, which was also conducted using 3-D artificial skin, and which involved the measurement of a quantity of secreted interleukin-1alpha (IL-1alpha), a pre-inflammatory mediator induced by SLS, we determined that the quantity of IL-1alpha in the 3-D artificial skin treated with 0.01 mg/ml and 0.05 mg/ml of levan was less than that registered in a skin sample that had been treated only with SLS. In this study, we determined that levan exerted an anti-inflammatory effect against inflammatory reactions to skin irritants, and also that levan exerted a cell-proliferative effect in bio-artificial skin, thereby indicating its potential applicability as a cosmeceutical agent.

Biodegradability testing of synthetic ester lubricants--effects of additives and usage.

The optimised biodegradability test system "O2/CO2 Headspace Test with GC-TCD" is used for the assessment of synthetic ester lubricants. The effects of both additives and usage on biodegradability are examined and discussed. Ester based cutting fluids and hydraulic fluids with and without additives are used under defined conditions at machine tools and hydraulic and plain bearing test benches. The lubricants are characterised additionally with respect to kinematic viscosity, acidity and elemental composition. Furthermore, a formulated mineral oil is characterised before and after usage at an hydraulic test bench. The results clearly show that the mineral oil is far less biodegradable than the ester oils and that their biodegradability is not affected by usage. Biodegradability of the ester oils is mainly depending on the characteristics of the base fluids and not affected by the additives. Antioxidants are influencing stability respectively biodegradability indirectly, since they prevent oxopolymerisation effects. Other effects of usage on biodegradation are not detected. In this context, the antioxidants ensure ready biodegradability and have a positive effect on the environmental fate of synthetic ester lubricants.

Hydroxylation of lauramide diethanolamine by liver microsomes.

Lauramide diethanolamine (LDEA)--a compound used in cosmetics and soap products as an emollient, thickener, and foam stabilizer--was observed to be metabolized by rat liver microsomes to two major products that were identified by GC/MS to be the 11-hydroxy and 12-hydroxy derivatives of LDEA. The specific activities for LDEA 11- and 12-hydroxylation in microsomes prepared from control rats were 2.23 +/- 0.40 and 0.71 +/- 0.17 nmol/min/mg protein, respectively. Treatment of rats with the cytochrome P4504A inducer and peroxisome proliferator, diethylhexyl phthalate, increased the LDEA 12-hydroxylation rate to 3.50 +/- 0.48 nmol/min/mg protein, a 5-fold increase in specific activity, whereas the LDEA 11-hydroxylase activity remained unchanged. Because LDEA contains a 12-carbon side chain, LDEA hydroxylation rates were compared with the hydroxylation rates for lauric acid. The specific activities of lauric acid 11- and 12-hydroxylation reactions in diethylhexyl phthalate-treated rats were 1.7-fold and 3.2-fold greater than the LDEA 11- and 12-hydroxylation rates, respectively. When LDEA hydroxylation reactions were performed in the presence of a polyclonal antibody to the rat P4504A forms, formation of 12-hydroxy-LDEA was inhibited by 80%. Rat kidney microsomes also supported the hydroxylation of LDEA at its 11- and 12-carbon atoms, with specific activities of 0.05 +/- 0.01 and 0.28 +/- 0.02 nmol/min/mg protein, respectively. LDEA was also metabolized to 11- and 12-hydroxy derivatives by human liver microsomes at specific activities of 0.22 +/- 0.06 and 0.84 +/- 0.26 nmol/min/mg protein, respectively.