Stratum corneum dysfunction in dandruff

PubMed Central

Turner, G A; Hoptroff, M; Harding, C R

2012-01-01

Summary Synopsis Dandruff is characterized by a flaky, pruritic scalp and affects up to half the world’s population post-puberty. The aetiology of dandruff is multifactorial, influenced by Malassezia, sebum production and individual susceptibility. The commensal yeast Malassezia is a strong contributory factor to dandruff formation, but the presence of Malassezia on healthy scalps indicates that Malassezia alone is not a sufficient cause. A healthy stratum corneum (SC) forms a protective barrier to prevent water loss and maintain hydration of the scalp. It also protects against external insults such as microorganisms, including Malassezia, and toxic materials. Severe or chronic barrier damage can impair proper hydration, leading to atypical epidermal proliferation, keratinocyte differentiation and SC maturation, which may underlie some dandruff symptoms. The depleted and disorganized structural lipids of the dandruff SC are consistent with the weakened barrier indicated by elevated transepidermal water loss. Further evidence of a weakened barrier in dandruff includes subclinical inflammation and higher susceptibility to topical irritants. We are proposing that disruption of the SC of the scalp may facilitate dandruff generation, in part by affecting susceptibility to metabolites from Malassezia. Treatment of dandruff with cosmetic products to directly improve SC integrity while providing effective antifungal activity may thus be beneficial. Résumé Les pellicules se caractérisent par un cuir chevelu prurigineux, squameux, et affectent jusqu’à la moitié de la population post-pubertaire du monde. L’étiologie des pellicules est multifactorielle, influencée par Malassezia, par la production de sébum, et par la susceptibilité individuelle. La levure commensale Malassezia est un facteur fortement contributif à la formation de pellicules, mais la présence de Malassezia aussi sur les cuirs chevelus sains indique que Malassezia seule n’est pas une cause

Biochemical changes in desmosomes of bovine muzzle epidermis during differentiation.

PubMed

Konohana, A; Konohana, I; Roberts, G P; Marks, R

1987-10-01

Biochemical changes taking place in desmosomes during differentiation have been studied. Bovine muzzle epidermis was sliced horizontally into 6 layers, 0.2 mm thick, and desmosomes were isolated from each layer. These were then analyzed by polyacrylamide gel electrophoresis. The electrophoretic patterns of desmosomal proteins from the 6 layers were found to be qualitatively similar to each other, but there was an increase in the ratio of the amount of 150 kD glycoprotein (desmoglein I) relative to 240 and 210 kD proteins (desmoplakins) in the upper layers of the epidermis. This finding was supported by the similar increase observed in electrophoretic patterns of proteins extracted directly from each layer of the epidermis in electrophoretic sample buffer. In order to study the fate of desmosomal components in the stratum corneum, serial skin surface biopsies were stained with antisera against desmosomal components using indirect immunofluorescence techniques. This experiment showed that desmosomal proteins and glycoproteins persist in the stratum corneum but quantitatively decrease in the outer layers. This decrease may play a significant role in desquamation.

The Clinical Relevance of Maintaining the Functional Integrity of the Stratum Corneum in both Healthy and Disease-affected Skin

PubMed Central

Del Rosso, James Q.; Levin, Jacqueline

2011-01-01

It has been recognized for approximately 50 years that the stratum corneum exhibits biological properties that contribute directly to maintaining and sustaining healthy skin. Continued basic science and clinical research coupled with keen clinical observation has led to more recent recognition and general acceptance that the stratum corneum completes many vital “barrier” tasks, including but not limited to regulating epidermal water content and the magnitude of water loss; mitigating exogenous oxidants that can damage components of skin via an innate antioxidant system; preventing or limiting cutaneous infection via multiple antimicrobial peptides; responding via innate immune mechanisms to “cutaneous invaders” of many origins, including microbes, true allergens, and other antigens; and protecting its neighboring cutaneous cells and structures that lie beneath from damaging effects of ultraviolet radiation. Additionally, specific abnormalities of the stratum corneum are associated with the clinical expression of certain disease states. This article provides a thorough “primer” for the clinician, reviewing the multiple normal homeostatic functions of the stratum corneum and the cutaneous challenges that arise when individual functions of this thin yet very active epidermal layer are compromised by exogenous and/or endogenous factors. PMID:21938268

In vitro models to estimate drug penetration through the compromised stratum corneum barrier.

PubMed

Engesland, André; Škalko-Basnet, Nataša; Flaten, Gøril Eide

2016-11-01

The phospholipid vesicle-based permeation assay (PVPA) is a recently established in vitro stratum corneum model to estimate the permeability of intact and healthy skin. The aim here was to further evolve this model to mimic the stratum corneum in a compromised skin barrier by reducing the barrier functions in a controlled manner. To mimic compromised skin barriers, PVPA barriers were prepared with explicitly defined reduced barrier function and compared with literature data from both human and animal skin with compromised barrier properties. Caffeine, diclofenac sodium, chloramphenicol and the hydrophilic marker calcein were tested to compare the PVPA models with established models. The established PVPA models mimicking the stratum corneum in healthy skin showed good correlation with biological barriers by ranking drugs similar to those ranked by the pig ear skin model and were comparable to literature data on permeation through healthy human skin. The PVPA models provided reproducible and consistent results with a distinction between the barriers mimicking compromised and healthy skin. The trends in increasing drug permeation with an increasing degree of compromised barriers for the model drugs were similar to the literature data from other in vivo and in vitro models. The PVPA models have the potential to provide permeation predictions when investigating drugs or cosmeceuticals intended for various compromised skin conditions and can thus possibly reduce the time and cost of testing as well as the use of animal testing in the early development of drug candidates, drugs and cosmeceuticals.

Characterization of Skin Friction Coefficient, and Relationship to Stratum Corneum Hydration in a Normal Chinese Population

PubMed Central

Zhu, Y.H.; Song, S.P.; Luo, W.; Elias, P.M.; Man, M.Q.

2011-01-01

Background and Objectives Studies have demonstrated that some cutaneous biophysical properties vary with age, gender and body sites. However, the characteristics of the skin friction coefficient in different genders and age groups have not yet been well established. In the present study, we assess the skin friction coefficient in a larger Chinese population. Methods A total of 633 subjects (300 males and 333 females) aged 0.15–79 years were enrolled. A Frictiometer® FR 770 and Corneometer® CM 825 (C&K MPA 5) were used to measure the skin friction coefficient and stratum corneum hydration, respectively, on the dorsal surface of the hand, the forehead and the canthus. Results In the females, the maximum skin friction coefficients on both the canthus and the dorsal hand skin were observed around the age of 40 years. In the males, the skin friction coefficient on the dorsal hand skin gradually increased from 0 to 40 years of age, and changed little afterward. Skin friction coefficients on some body sites were higher in females than in age-matched males in some age groups. On the canthus and the dorsal hand skin of females, a positive correlation was found between skin friction coefficient and stratum corneum hydration (p < 0.001 and p < 0.0001, respectively). In contrast, in males, the skin friction coefficient was positively correlated with stratum corneum hydration on the forehead and the dorsal hand skin (p < 0.05 and p < 0.0001, respectively). Conclusion The skin friction coefficient varies with age, gender and body site, and positively correlates with stratum corneum hydration on some body sites. PMID:21088455

Characterization of skin friction coefficient, and relationship to stratum corneum hydration in a normal Chinese population.

PubMed

Zhu, Y H; Song, S P; Luo, W; Elias, P M; Man, M Q

2011-01-01

Studies have demonstrated that some cutaneous biophysical properties vary with age, gender and body sites. However, the characteristics of the skin friction coefficient in different genders and age groups have not yet been well established. In the present study, we assess the skin friction coefficient in a larger Chinese population. A total of 633 subjects (300 males and 333 females) aged 0.15-79 years were enrolled. A Frictiometer FR 770 and Corneometer CM 825 (C&K MPA 5) were used to measure the skin friction coefficient and stratum corneum hydration, respectively, on the dorsal surface of the hand, the forehead and the canthus. In the females, the maximum skin friction coefficients on both the canthus and the dorsal hand skin were observed around the age of 40 years. In the males, the skin friction coefficient on the dorsal hand skin gradually increased from 0 to 40 years of age, and changed little afterward. Skin friction coefficients on some body sites were higher in females than in age-matched males in some age groups. On the canthus and the dorsal hand skin of females, a positive correlation was found between skin friction coefficient and stratum corneum hydration (p < 0.001 and p < 0.0001, respectively). In contrast, in males, the skin friction coefficient was positively correlated with stratum corneum hydration on the forehead and the dorsal hand skin (p < 0.05 and p < 0.0001, respectively). The skin friction coefficient varies with age, gender and body site, and positively correlates with stratum corneum hydration on some body sites. Copyright © 2010 S. Karger AG, Basel.

Measurements of glucose on the skin surface, in stratum corneum and in transcutaneous extracts: implications for physiological sampling.

PubMed

Cunningham, David D; Young, Douglas F

2003-09-01

Obtaining representative physiological samples for glucose analysis remains a challenge especially when developing less invasive glucose monitoring systems for diabetic patients. In the present study the glucose content of the stratum corneum was compared with the amount of glucose obtained by short aqueous extractions from a site on the dorsal wrist, using high pressure liquid chromatography with pulsed amperometric detection. Ten successive aqueous 1-minute extractions of the site yielded a total of 60 ng cm(-2). The total glucose content of the stratum corneum of the site, determined from 30 successive tape-strippings of the site, was 360 ng cm(-2). After tape-stripping, the transcutaneous aqueous extraction rate was 86 +/- 13 ng cm(-2) min(-1), compared with rates of 80-600 ng cm(-2) min(-1) obtained with suction effusion or microdialysis after tape-stripping. Glucose on the surface of the skin and within the stratum corneum should be considered as sources of extraneous glucose contamination during testing of less invasive glucose monitoring devices.

Dehydration of multilamellar fatty acid membranes: Towards a computational model of the stratum corneum

NASA Astrophysics Data System (ADS)

MacDermaid, Christopher M.; DeVane, Russell H.; Klein, Michael L.; Fiorin, Giacomo

2014-12-01

The level of hydration controls the cohesion between apposed lamellae of saturated free fatty acids found in the lipid matrix of stratum corneum, the outermost layer of mammalian skin. This multilamellar lipid matrix is highly impermeable to water and ions, so that the local hydration shell of its fatty acids may not always be in equilibrium with the acidity and relative humidity, which significantly change over a course of days during skin growth. The homeostasis of the stratum corneum at each moment of its growth likely requires a balance between two factors, which affect in opposite ways the diffusion of hydrophilic species through the stratum corneum: (i) an increase in water order as the lipid lamellae come in closer contact, and (ii) a decrease in water order as the fraction of charged fatty acids is lowered by pH. Herein molecular dynamics simulations are employed to estimate the impact of both effects on water molecules confined between lamellae of fatty acids. Under conditions where membrane undulations are energetically favorable, the charged fatty acids are able to sequester cations around points of contact between lamellae that are fully dehydrated, while essentially maintaining a multilamellar structure for the entire system. This observation suggests that the undulations of the fatty acid lamellae control the diffusion of hydrophilic species through the water phase by altering the positional and rotational order of water molecules in the embedded/occluded "droplets."

Phase behavior of stratum corneum lipids in mixed Langmuir-Blodgett monolayers.

PubMed Central

ten Grotenhuis, E; Demel, R A; Ponec, M; Boer, D R; van Miltenburg, J C; Bouwstra, J A

1996-01-01

The lipids found in the bilayers of the stratum corneum fulfill the vital barrier role of mammalian bodies. The main classes of lipids found in stratum corneum are ceramides, cholesterol, and free fatty acids. For an investigation of their phase behavior, mixed Langmuir-Blodgett monolayers of these lipids were prepared. Atomic force microscopy was used to investigate the structure of the monolayers as a function of the monolayer composition. Three different types of ceramide were used: ceramide extracted from pigskin, a commercially available ceramide with several fatty acid chain lengths, and two synthetic ceramides that have only one fatty acid chain length. In pigskin ceramide-cholesterol mixed monolayers phase separation was observed. This phase separation was also found for the commercially available type III Sigma ceramide-cholesterol mixed monolayers with molar ratios ranging from 1:0.1 to 1:1. These monolayers separated into two phases, one composed of the long fatty acid chain fraction of Sigma ceramide III and the other of the short fatty acid chain fraction of Sigma ceramide III mixed with cholesterol. Mixtures with a higher cholesterol content consisted of only one phase. These observations were confirmed by the results obtained with synthetic ceramides, which have only one fatty acid chain length. The synthetic ceramide with a palmitic acid (16:0) chain mixed with cholesterol, and the synthetic ceramide with a lignoceric acid (24:0) chain did not. Free fatty acids showed a preference to mix with one of these phases, depending on their fatty acid chain lengths. The results of this investigation suggest that the model system used in this study is in good agreement with those of other studies concerning the phase behavior of the stratum corneum lipids. By varying the composition of the monolayers one can study the role of each lipid class in detail. Images FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 PMID:8874014

Removal of adhesive wound dressing and its effects on the stratum corneum of the skin: comparison of eight different adhesive wound dressings.

PubMed

Matsumura, Hajime; Imai, Ryutaro; Ahmatjan, Niyaz; Ida, Yukiko; Gondo, Masahide; Shibata, Dai; Wanatabe, Katsueki

2014-02-01

In recent years, adhesive wound dressings have been increasingly applied postoperatively because of their ease of use as they can be kept in place without having to cut and apply surgical tapes and they can cover a wound securely. However, if a wound dressing strongly adheres to the wound, a large amount of stratum corneum is removed from the newly formed epithelium or healthy periwound skin. Various types of adhesives are used on adhesive wound dressings and the extent of skin damage depends on how much an adhesive sticks to the wound or skin surface. We quantitatively determined and compared the amount of stratum corneum removed by eight different wound dressings including polyurethane foam using acrylic adhesive, silicone-based adhesive dressing, composite hydrocolloid and self-adhesive polyurethane foam in healthy volunteers. The results showed that wound dressings with silicone adhesive and self-adhesive polyurethane foam removed less stratum corneum, whereas composite hydrocolloid and polyurethane foam using acrylic adhesive removed more stratum corneum. © 2012 The Authors. International Wound Journal © 2012 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Usefulness of pressure-sensitive adhesives as a pretreatment material before application of topical drug formulations and a peeling tape for excess stratum corneum layers.

PubMed

Kikuchi, Keisuke; Todo, Hiroaki; Sugibayashi, Kenji

2014-01-01

Two unique pressure-sensitive adhesive (PSA) tapes (PSA-A, -B) with different adhesive properties of commercial PSAs were prepared and evaluated for their usefulness as a pretreatment material prior to the application of transdermal therapeutic systems or topical drug formulations and also as a peeling agent against excess layers of the stratum corneum. In the present study, in vitro permeation experiments were conducted using vertical type diffusion cells and excised hairless rat or porcine skin from which the stratum corneum had been stripped several times with PSAs. The results obtained revealed that PSA-A and -B had higher stripping or peeling effects than those of the marketed PSAs. Marked changes were observed in skin barrier function before and after stripping using PSAs, and the enhancement effect on the skin permeation of drugs achieved by stripping the stratum corneum was markedly different between the PSAs. PSA-A, in particular, markedly improved skin permeation and the skin concentration of topically applied chemical compounds because it removed many layers of the stratum corneum when skin was stripped only a few times. In contrast, when PSA-B was used to pretreat the skin surface, the extent of skin permeation and concentration of drugs was safely increased because only a few layers of the stratum corneum were removed, even with repeated stripping. The enhancement effect achieved by PSA-B was not as high as that by PSA-A. Thus, stripping with PSA-A can be used as a penetration enhancement tool, whereas PSA-B can be used as a peeling material against excess layers of the stratum corneum.

Mathematical Description of the Uptake of Hydrocarbons in Jet Fuel into the Stratum Corneum of Human Volunteers

PubMed Central

Kim, David; Farthing, Matthew W.; Miller, Cass T.; Nylander-French, Leena A.

2008-01-01

The objective of this research was to develop a mathematical description of uptake of aromatic and aliphatic hydrocarbons into the stratum corneum of human skin in vivo. A simple description based on Fick’s Laws of diffusion was used to predict the spatiotemporal variation of naphthalene, 1- and 2-methylnaphthalene, undecane, and dodecane in the stratum corneum of human volunteers. The estimated values of the diffusion coefficients for each chemical were comparable to values predicted using in vitro skin systems and biomonitoring studies. These results demonstrate the value of measuring dermal exposure using the tape-strip technique and the importance of quantifying of dermal uptake. PMID:18423910

Non-invasive quantification of melanin in the stratum corneum: a novel indicator of skin lesions in pigmentation diseases.

PubMed

Matsunaka, H; Yamamoto, Y; Furukawa, F

2017-02-01

Skin melanin content is an important indicator for ascertaining the pathology of skin pigmentation diseases, but its analysis necessitates a biopsy or other means of collecting tissue, posing a considerable burden to the patient, and making it difficult to observe how a given skin site changes over time. Here, we aimed to establish a non-invasive method for quantifying the eumelanin and pheomelanin content of the stratum corneum. Sun-exposed and non-exposed samples from 10 healthy Japanese subjects were compared. We harvested the outermost layer of the stratum corneum by tape-stripping, considering the outer side of the forearm as a sun-exposed area, and medial side of the upper arm as a non-exposed area. Four additional subjects were included in the analysis of change in melanin content over time at the same skin site. The anterior lower leg received a single exposure to two minimal erythema dose sunlight, and the stratum corneum was harvested from the same site over a period of 20 weeks; we subsequently quantified the levels of eumelanin and pheomelanin using high-performance liquid chromatography. We were able to accurately quantify the eumelanin and pheomelanin contents of the stratum corneum, and to observe the evolution of the same skin site over time. Eumelanin levels were significantly higher in the sun-exposed area, with a peak in melanin observed after 11-15 weeks of sun exposure. This non-invasive method can serve as a marker for pathology of skin pigmentation diseases such as malignant tumors. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of stratum corneum heterogeneity, anisotropy, asymmetry and follicular pathway on transdermal penetration.

PubMed

Barbero, Ana M; Frasch, H Frederick

2017-08-28

The impact of the complex structure of the stratum corneum on transdermal penetration is not yet fully described by existing models. A quantitative and thorough study of skin permeation is essential for chemical exposure assessment and transdermal delivery of drugs. The objective of this study is to analyze the effects of heterogeneity, anisotropy, asymmetry, follicular diffusion, and location of the main barrier of diffusion on percutaneous permeation. In the current study, the solution of the transient diffusion through a two-dimensional-anisotropic brick-and-mortar geometry of the stratum corneum is obtained using the commercial finite element program COMSOL Multiphysics. First, analytical solutions of an equivalent multilayer geometry are used to determine whether the lipids or corneocytes constitute the main permeation barrier. Also these analytical solutions are applied for validations of the finite element solutions. Three illustrative compounds are analyzed in these sections: diethyl phthalate, caffeine and nicotine. Then, asymmetry with depth and follicular diffusion are studied using caffeine as an illustrative compound. The following findings are drawn from this study: the main permeation barrier is located in the lipid layers; the flux and lag time of diffusion through a brick-and-mortar geometry are almost identical to the values corresponding to a multilayer geometry; the flux and lag time are affected when the lipid transbilayer diffusivity or the partition coefficients vary with depth, but are not affected by depth-dependent corneocyte diffusivity; and the follicular contribution has significance for low transbilayer lipid diffusivity, especially when flux between the follicle and the surrounding stratum corneum is involved. This study demonstrates that the diffusion is primarily transcellular and the main barrier is located in the lipid layers. Published by Elsevier B.V.

Comparison of rat epidermal keratinocyte organotypic culture (ROC) with intact human skin: lipid composition and thermal phase behavior of the stratum corneum.

PubMed

Pappinen, Sari; Hermansson, Martin; Kuntsche, Judith; Somerharju, Pentti; Wertz, Philip; Urtti, Arto; Suhonen, Marjukka

2008-04-01

The present report is a part of our continuing efforts to explore the utility of the rat epidermal keratinocyte organotypic culture (ROC) as an alternative model to human skin in transdermal drug delivery and skin irritation studies of new chemical entities and formulations. The aim of the present study was to compare the stratum corneum lipid content of ROC with the corresponding material from human skin. The lipid composition was determined by thin-layer chromatography (TLC) and mass-spectrometry, and the thermal phase transitions of stratum corneum were studied by differential scanning calorimetry (DSC). All major lipid classes of the stratum corneum were present in ROC in a similar ratio as found in human stratum corneum. Compared to human skin, the level of non-hydroxyacid-sphingosine ceramide (NS) was increased in ROC, while alpha-hydroxyacid-phytosphingosine ceramide (AP) and non-hydroxyacid-phytosphingosine ceramides (NP) were absent. Also some alterations in fatty acid profiles of ROC ceramides were noted, e.g., esterified omega-hydroxyacid-sphingosine contained increased levels of oleic acid instead of linoleic acid. The fraction of lipids covalently bound to corneocyte proteins was distinctly lower in ROC compared to human skin, in agreement with the results from DSC. ROC underwent a lipid lamellar order to disorder transition (T2) at a slightly lower temperature (68 degrees C) than human skin (74 degrees C). These differences in stratum corneum lipid composition and the thermal phase transitions may explain the minor differences previously observed in drug permeation between ROC and human skin.

Molecular dynamics simulations of stratum corneum lipid models: fatty acids and cholesterol.

PubMed

Höltje, M; Förster, T; Brandt, B; Engels, T; von Rybinski, W; Höltje, H D

2001-03-09

We report the results of an investigation on stratum corneum lipids, which present the main barrier of the skin. Molecular dynamics simulations, thermal analysis and FTIR measurements were applied. The primary objective of this work was to study the effect of cholesterol on skin structure and dynamics. Two molecular models were constructed, a free fatty acid bilayer (stearic acid, palmitic acid) and a fatty acid/cholesterol mixture at a 1:1 molar ratio. Our simulations were performed at constant pressure and temperature on a nanosecond time scale. The resulting model structures were characterized by calculating surface areas per headgroup, conformational properties, atom densities and order parameters of the fatty acids. Analysis of the simulations indicates that the free fatty acid fraction of stratum corneum lipids stays in a highly ordered crystalline state at skin temperatures. The phase behavior is strongly influenced when cholesterol is added. Cholesterol smoothes the rigid phases of the fatty acids: the order of the hydrocarbon tails (mainly of the last eight bonds) is reduced, the area per molecule becomes larger, the fraction of trans dihedrals is lower and the hydrophobic thickness is reduced. The simulation results are in good agreement with our experimental data from FTIR analysis and NIR-FT Raman spectroscopy.

Nanoscale infrared (IR) spectroscopy and imaging of structural lipids in human stratum corneum using an atomic force microscope to directly detect absorbed light from a tunable IR laser source.

PubMed

Marcott, Curtis; Lo, Michael; Kjoller, Kevin; Domanov, Yegor; Balooch, Guive; Luengo, Gustavo S

2013-06-01

An atomic force microscope (AFM) and a tunable infrared (IR) laser source have been combined in a single instrument (AFM-IR) capable of producing ~200-nm spatial resolution IR spectra and absorption images. This new capability enables IR spectroscopic characterization of human stratum corneum at unprecendented levels. Samples of normal and delipidized stratum corneum were embedded, cross-sectioned and mounted on ZnSe prisms. A pulsed tunable IR laser source produces thermomechanical expansion upon absorption, which is detected through excitation of contact resonance modes in the AFM cantilever. In addition to reducing the total lipid content, the delipidization process damages the stratum corneum morphological structure. The delipidized stratum corneum shows substantially less long-chain CH2 -stretching IR absorption band intensity than normal skin. AFM-IR images that compare absorbances at 2930/cm (lipid) and 3290/cm (keratin) suggest that regions of higher lipid concentration are located at the perimeter of corneocytes in the normal stratum corneum. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Induction of a Hardening Phenomenon and Quantitative Changes of Ceramides in Stratum Corneum

PubMed Central

Park, Sook Young; Kim, Jin Hye; Cho, Soo Ick; Kim, Kyeong Il; Cho, Hee Jin; Park, Chun Wook; Lee, Cheol Heon

2014-01-01

Background Hardening phenomenon of human skin after repeated exposure to the irritants is well-known, but the precise mechanism remains elusive. Objective To modify the previous experimental model of hardening phenomenon by repeated applications of two different concentrations of sodium lauryl sulfate (SLS) solutions to Korean healthy volunteers and to investigate the quantitative changes of ceramides in stratum corneum before and after chronic repeated irritation. Methods Eight hundred microliters of distilled water containing 0.1% and 2% SLS was applied for 10 minutes on the forearm of 41 healthy volunteers for 3 weeks. After an intervening 3-week rest, 24-hour patch tests with 1% SLS were conducted on previously irritated sites. Transepidermal water loss (TEWL), erythema index and quantity of ceramide were measured in the stratum corneum before and after irritation. Results TEWL values on the sites preirritated with 2% SLS were lower than those with 0.1% SLS. Hardening phenomenon occurred in 24 volunteers at day 44. The changes in ceramide levels were not significantly higher in the hardened skin than in the non-hardened skin. Conclusion Repetitive stimulation with a higher concentration of SLS can more easily trigger skin hardening. PMID:24648684

Mechanics, morphology, and mobility in stratum corneum membranes

NASA Astrophysics Data System (ADS)

Olmsted, Peter; Das, Chinmay; Noro, Massimo

2012-02-01

The stratum corneum is the outermost layer of skin, and serves as a protective barrier against external agents, and to control moisture. It comprises keratin bodies (corneocytes) embedded in a matrix of lipid bilayers. Unlike the more widely studied phospholipid bilayers, the SC bilayers are typically in a gel-like state. Moreover, the SC membrane composition is radically different from more fluid counterparts: it comprises single tailed fatty acids, ceramides, and cholesterol; with many distinct ceramides possessing different lengths of tails, and always with two tails of different lengths. I will present insight from computer simulations into the morphology, mechanical properties, and diffusion (barrier) properties of these highly heterogeneous membranes. Our results provide some clue as to the design principles for the SC membrane, and is an excellent example of the use of wide polydispersity by natural systems.

Role of ascorbic acid in stratum corneum lipid models exposed to UV irradiation.

PubMed

Trommer, Hagen; Böttcher, Roif; Pöppl, Andreas; Hoentsch, Joachim; Wartewig, Siegfried; Neubert, Reinhard H H

2002-07-01

The effects of ascorbic acid on Stratum corneum lipid models following ultraviolet irradiation were studied adding iron ions as transition metal catalysts. Lipid peroxidation was quantified by the thiobarbituric acid assay. The qualitative changes were studied on a molecular level by mass spectrometry. To elucidate the nature of free radical involvement we carried out electron paramagnetic resonance studies. The influence of ascorbic acid on the concentration of hydroxyl radicals was examined using the spin trapping technique. Moreover, we checked the vitamin's ability to react with stable radicals. Ascorbic acid was found to have prooxidative effects in all lipid systems in a concentration dependent manner. The degradation products of ascorbic acid after its prooxidative action were detected. The concentration of the hydroxyl radicals in the Fenton assay was decreased by ascorbic acid. The quantification assay of 2,2-diphenyl-1-picrylhydrazyl hydrate showed reduced concentration levels of the stable radical caused by ascorbic acid. Considering human skin and its constant exposure to UV light and oxygen, an increased pool of iron ions in irradiated skin and the depletion of co-antioxidants, the administration of ascorbic acid in cosmetic formulations or in sunscreens could unfold adverse effects among the Stratum corneum lipids.

Lipid composition of the stratum corneum and cutaneous water loss in birds along an aridity gradient.

PubMed

Champagne, Alex M; Muñoz-Garcia, Agustí; Shtayyeh, Tamer; Tieleman, B Irene; Hegemann, Arne; Clement, Michelle E; Williams, Joseph B

2012-12-15

Intercellular and covalently bound lipids within the stratum corneum (SC), the outermost layer of the epidermis, are the primary barrier to cutaneous water loss (CWL) in birds. We compared CWL and intercellular SC lipid composition in 20 species of birds from desert and mesic environments. Furthermore, we compared covalently bound lipids with CWL and intercellular lipids in the lark family (Alaudidae). We found that CWL increases in birds from more mesic environments, and this increase was related to changes in intercellular SC lipid composition. The most consistent pattern that emerged was a decrease in the relative amount of cerebrosides as CWL increased, a pattern that is counterintuitive based on studies of mammals with Gaucher disease. Although covalently bound lipids in larks did not correlate with CWL, we found that covalently bound cerebrosides correlated positively with intercellular cerebrosides and intercellular cholesterol ester, and intercellular cerebrosides correlated positively with covalently bound free fatty acids. Our results led us to propose a new model for the organization of lipids in the avian SC, in which the sugar moieties of cerebrosides lie outside of intercellular lipid layers, where they may interdigitate with adjacent intercellular cerebrosides or with covalently bound cerebrosides.

Subclass distribution of IgG antibodies to the rat oesophagus stratum corneum (so-called anti-keratin antibodies) in rheumatoid arthritis.

PubMed Central

Vincent, C; Serre, G; Basile, J P; Lestra, H C; Girbal, E; Sebbag, M; Soleilhavoup, J P

1990-01-01

Serum IgG, labelling the stratum corneum of the rat oesophagus epithelium, so-called anti-keratin antibodies (AKA) constitute the most specific marker for the diagnosis of rheumatoid arthritis. In this study, we investigated 31 IgG AKA-positive rheumatoid sera and 21 control sera from patients with non-rheumatoid inflammatory rheumatic diseases. The serum level of IgG1,2,3 and 4 was determined by radial immunodiffusion and the subclass distribution of IgG AKA by a three-step semi-quantitative immunofluorescence assay using standard monoclonal antibodies specific for each of the four human IgG subclasses. In the rheumatoid sera, the serum level of IgG1 was found to be significantly increased and the level of IgG2 significantly decreased with regard to the control sera, while the levels of IgG3 and 4 as well as total IgG were in the normal range. IgG1,2,3, and 4 AKA were detected in 27 (87%), 6 (19%), 4 (13%) and 11 (35%) of the 31 rheumatoid sera, respectively, and were found to be independent of the clinical and biological indices of the disease. In spite of inter-individual heterogeneity, two predominant profiles were distinguished: IgG1 (alone) and IgG(1 + 4), which together represented 18 sera (58%). The large predominance of IgG1 AKA and the quasi-absence of IgG2 AKA suggest that the recognized antigen may be partly comprised of protein. Moreover, the high frequency of occurrence of IgG4 AKA might result from chronic exposure to the eliciting antigen, which could be a genuine autoantigen since we demonstrated that it is also present in the stratum corneum of human epidermis. Images Fig. 1 PMID:1696185

Comparison of gravimetric and spectroscopic approaches to quantify stratum corneum removed by tape-stripping.

PubMed

Mohammed, D; Yang, Q; Guy, R H; Matts, P J; Hadgraft, J; Lane, M E

2012-09-01

Skin surface tape-stripping is an extensively used technique to examine the distribution profile, penetration and safety of various active compounds. It is also a widely accepted method to probe skin barrier properties and more specifically, those of the stratum corneum (SC). The amount of SC removed by tape-stripping is generally determined either gravimetrically or by extraction and measurement of SC proteins. A novel infra-red densitometry (IRD) technique has recently been introduced to measure SC protein content. In the present study, IRD was investigated as an alternative method to measure the mass of SC removed by tape-stripping. Tape-stripping experiments were conducted on human volunteers. The weight of the stratum corneum removed was assessed by the gravimetric approach and by IRD. Transepidermal water loss (TEWL) was also measured before and after each tape-strip. A linear correlation coefficient was obtained for the data from the gravimetric and IRD measurements (r(2)=0.65; n=240). IRD is therefore proposed as a rapid, non-destructive alternative to the gravimetric approach to estimate the amount of SC removed by tape-stripping in vivo. Copyright © 2012 Elsevier B.V. All rights reserved.

Cell proliferation in normal epidermis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weinstein, G.D.; McCullough, J.L.; Ross, P.

1984-06-01

A detailed examination of cell proliferation kinetics in normal human epidermis is presented. Using tritiated thymidine with autoradiographic techniques, proliferative and differentiated cell kinetics are defined and interrelated. The proliferative compartment of normal epidermis has a cell cycle duration (Tc) of 311 h derived from 3 components: the germinative labeling index (LI), the duration of DNA synthesis (ts), and the growth fraction (GF). The germinative LI is 2.7% +/- 1.2 and ts is 14 h, the latter obtained from a composite fraction of labeled mitoses curve obtained from 11 normal subjects. The GF obtained from the literature and from humanmore » skin xenografts to nude mice is estimated to be 60%. Normal-appearing epidermis from patients with psoriasis appears to have a higher proliferation rate. The mean LI is 4.2% +/- 0.9, approximately 50% greater than in normal epidermis. Absolute cell kinetic values for this tissue, however, cannot yet be calculated for lack of other information on ts and GF. A kinetic model for epidermal cell renewal in normal epidermis is described that interrelates the rate of birth/entry, transit, and/or loss of keratinocytes in the 3 epidermal compartments: proliferative, viable differentiated (stratum malpighii), and stratum corneum. Expected kinetic homeostasis in the epidermis is confirmed by the very similar ''turnover'' rates in each of the compartments that are, respectively, 1246, 1417, and 1490 cells/day/mm2 surface area. The mean epidermal turnover time of the entire tissue is 39 days. The Tc of 311 h in normal cells in 8-fold longer than the psoriatic Tc of 36 h and is necessary for understanding the hyperproliferative pathophysiologic process in psoriasis.« less

Evaluation of the effect of zinc acetate on the stratum corneum penetration kinetics of erythromycin in healthy male volunteers.

PubMed

van Hoogdalem, E J; Terpstra, I J; Baven, A L

1996-01-01

Erythromycin with or without additional zinc acetate is used topically in the treatment of acne vulgaris. A potential effect of zinc on the stratum corneum penetration of erythromycin was investigated in human volunteers. Skin surface washings and tape strippings from the skin of the back were collected after drug applications in 12 subjects for quantification of erythromycin levels. Zinc acetate increased the amount remaining on the back skin at 6 h after application from 40 +/- 19 to 56 +/- 15% of the dose and, vice versa, reduced the amount in stratum corneum strips from 22 +/- 7 to 18 +/- 7%, both with statistical significance. The effect varied with body region. Zinc acetate thus provided to prolong the residence time of erythromycin on the skin.

Stratum corneum hydration and skin surface pH in patients with atopic dermatitis.

PubMed

Knor, Tanja; Meholjić-Fetahović, Ajša; Mehmedagić, Aida

2011-01-01

Atopic dermatitis (AD) is a chronically relapsing skin disease with genetic predisposition, which occurs most frequently in preschool children. It is considered that dryness and pruritus, which are always present in AD, are in correlation with degradation of the skin barrier function. Measurement of hydration and pH value of the stratum corneum is one of the noninvasive methods for evaluation of skin barrier function. The aim of the study was to assess skin barrier function by measuring stratum corneum hydration and skin surface pH of the skin with lesions, perilesional skin and uninvolved skin in AD patients, and skin in a healthy control group. Forty-two patients were included in the study: 21 young and adult AD patients and 21 age-matched healthy controls. Capacitance, which is correlated with hydration of stratum corneum and skin surface pH were measured on the forearm in the above areas by SM810/CM820/pH900 combined units (Courage AND Khazaka, Germany). The mean value of water capacitance measured in AD patients was 44.1 ± 11.6 AU (arbitrary units) on the lesions, 60.2 ± 12.4 AU on perilesional skin and 67.2 ± 8.8 AU on uninvolved skin. In healthy controls, the mean value was 74.1 ± 9.2 AU. The mean pH value measured in AD patients was 6.13 ± 0.52 on the lesions, 5.80 ± 0.41 on perilesional skin, and 5.54 ± 0.49 on uninvolved skin. In control group, the mean pH of the skin surface was 5.24 ± 0.40. The values of both parameters measured on lesional skin were significantly different (capacitance decreased and pH increased) from the values recorded on perilesional skin and uninvolved skin. The same held for the relation between perilesional and uninvolved skin. According to study results, the uninvolved skin of AD patients had significantly worse values of the measured parameters as compared with control group. The results of this study suggested the skin barrier function to be degraded in AD patients, which is specifically expressed in lesional skin.

[Impact of wet work on epidermal barrier (tewl and stratum corneum hydration) and skin viscoelasticity in nurses].

PubMed

Kieć-Świcrczyńska, Marta; Chomiczewska-Skóra, Dorota; Świerczyńska-Machura, Dominika; Kręcisz, Beata

2014-01-01

Nurses are prone to develop hand eczema due to occupational exposure to irritants, including wet work. The aim of the study was to evaluate the impact of wet work on selected skin properties, reflecting epidermal barrier function--transepidermal water loss (TEWL) and stratum corneum hydration--and additionally skin viscoelasticity, in nurses. Study subjects included 90 nurses employed in hospital wards. Measurements were carried out within the dorsal aspect of the dominant hand, using a Cutometer MPA 580 equipped with Tewameter TM 300 and Corneometer CM 825 (Courage & Khazaka, Germany) probes. Examina- tions took place on hospital premises. Similar measurements were performed in the control group of females non-exposed to irritants. In the examined group of nurses, mean TEWL was 15.5 g/h/m2 and was higher than in the control group (12.99 g/h/m2). After rejecting the extreme results, the difference between the groups proved to be statistically significant (p < 0.05). The mean value of stratum corneum hydration was lower in the examined group (37.915) compared with the control group (40.05), but the difference was not sta tistically significant. Also results of viscoelasticity assessment showed no significant differences between studied groups. The results of the assessment of skin biophysical properties show that wet work exerts a moderately adverse impact on skin condition. A higher TEWL value and a lower stratum corneum hydration in workers exposed to irritants reflect an adverse impact of these factors on the epidermal barrier function.

From observational to analytical morphology of the stratum corneum: progress avoiding hazardous animal and human testings

PubMed Central

Piérard, Gérald E; Courtois, Justine; Ritacco, Caroline; Humbert, Philippe; Fanian, Ferial; Piérard-Franchimont, Claudine

2015-01-01

Background In cosmetic science, noninvasive sampling of the upper part of the stratum corneum is conveniently performed using strippings with adhesive-coated discs (SACD) and cyanoacrylate skin surface strippings (CSSSs). Methods Under controlled conditions, it is possible to scrutinize SACD and CSSS with objectivity using appropriate methods of analytical morphology. These procedures apply to a series of clinical conditions including xerosis grading, comedometry, corneodynamics, corneomelametry, corneosurfametry, corneoxenometry, and dandruff assessment. Results With any of the analytical evaluations, SACD and CSSS provide specific salient information that is useful in the field of cosmetology. In particular, both methods appear valuable and complementary in assessing the human skin compatibility of personal skincare products. Conclusion A set of quantitative analytical methods applicable to the minimally invasive and low-cost SACD and CSSS procedures allow for a sound assessment of cosmetic effects on the stratum corneum. Under regular conditions, both methods are painless and do not induce adverse events. Globally, CSSS appears more precise and informative than the regular SACD stripping. PMID:25767402

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

PubMed

Christman, Jeremy C; Fix, Deborah K; Lucus, Sawanna C; Watson, Debrah; Desmier, Emma; Wilkerson, Rolanda J Johnson; Fixler, Charles

2012-01-01

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. 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. 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. 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.

Thermodynamic Insights and Conceptual Design of Skin-Sensitive Chitosan Coated Ceramide/PLGA Nanodrug for Regeneration of Stratum Corneum on Atopic Dermatitis

PubMed Central

Jung, Sang-Myung; Yoon, Gwang Heum; Lee, Hoo Chul; Jung, Moon Hee; Yu, Sun Il; Yeon, Seung Ju; Min, Seul Ki; Kwon, Yeo Seon; Hwang, Jin Ha; Shin, Hwa Sung

2015-01-01

Atopic dermatitis (AD) is a complex skin disease primarily characterized by psoriasis of the stratum corneum. AD drugs have usually been used in acidic and hydrophilic solvents to supply moisture and prevent lipid defects. Ceramide is a typical treatment agent to regenerate the stratum corneum and relieve symptoms of AD. However, ceramide has limitation on direct use for skin because of its low dispersion properties in hydrophilic phase and side effects at excessive treatment. In this study, ceramide imbedded PLGA nanoparticles were developed with chitosan coating (Chi-PLGA/Cer) to overcome this problem. The chitosan coating enhanced initial adherence to the skin and prevented the initial burst of ceramide, but was degraded by the weakly acidic nature of skin, resulting in controlled release of ceramide with additional driving force of the squeezed PLGA nanoparticles. Additionally, the coating kinetics of chitosan were controlled by manipulating the reaction conditions and then mathematically modeled. The Chi-PLGA/Cer was not found to be cytotoxic and ceramide release was controlled by pH, temperature, and chitosan coating. Finally, Chi-PLGA/Cer was demonstrated to be effective at stratum corneum regeneration in a rat AD model. Overall, the results presented herein indicated that Chi-PLGA/Cer is a novel nanodrug for treatment of AD. PMID:26666701

Leaching from the stratum corneum does not explain the previously reported elevated potassium ion concentration in sweat.

PubMed

Buono, Michael J; Stone, Michael; Cannon, Daniel T

2016-03-01

The purpose of this study was to determine if K+ is leached from the stratum corneum when sweat is present on the skin's surface. The results will help address whether sweat [K+] previously reported in the literature are artifactually elevated as a result of K+ leaching. Twelve (six female, six male) healthy volunteers participated in this study. After thorough skin cleansing and preparation with isopropyl alcohol and high-performance liquid chromatography-grade distilled water, three sites were chosen and a 50 μL drop of artificial sweat was pipetted directly onto the skin. The artificial sweat had a [K+] of 4 mEq·L-1, an osmolality of 120 mosm·L-1, and a pH of 6.0. Immediately following, a clear plastic cover slip (~6 cm2) with a shallow 0.8 cm2 convex impression in the center was applied over each drop, preventing evaporation. Each sample was allowed to sit on the forearm, under the plastic cover slip, for 10 min. The mean (±SD) [K+] in 'artificial' sweat not exposed to the skin was measured to be 4.2±0.4 mEq·L-1. After 10 min of exposure to the stratum corneum of the forearm, the artificial sweat had a mean (±SD) [K+] of 3.9±0.3 mEq·L-1. There was no significant difference (p>0.05) in the [K+] between the control artificial sweat and the samples collected after 10 min of exposure to forearm skin. These results do not support the hypothesis that significant K+ leaching from the stratum corneum into standing sweat is the cause for the previously reported elevated sweat [K+].

Incomplete KLK7 Secretion and Upregulated LEKTI Expression Underlie Hyperkeratotic Stratum Corneum in Atopic Dermatitis.

PubMed

Igawa, Satomi; Kishibe, Mari; Minami-Hori, Masako; Honma, Masaru; Tsujimura, Hisashi; Ishikawa, Junko; Fujimura, Tsutomu; Murakami, Masamoto; Ishida-Yamamoto, Akemi

2017-02-01

Atopic dermatitis (AD) is a common inflammatory skin disorder. Chronic AD lesions present hyperkeratosis, indicating a disturbed desquamation process. KLK7 is a serine protease involved in the proteolysis of extracellular corneodesmosome components, including desmocollin 1 and corneodesmosin, which leads to desquamation. KLK7 is secreted by lamellar granules and upregulated in AD lesional skin. However, despite increased KLK7 protein levels, immunostaining and electron microscopy indicated numerous corneodesmosomes remaining in the uppermost layer of the stratum corneum from AD lesions. We aimed to clarify the discrepancy between KLK7 overexpression and retention of corneodesmosomes on AD corneocytes. Western blot analysis indicated abnormal corneodesmosin degradation patterns in stratum corneum from AD lesions. The KLK activity of tape-stripped corneocytes from AD lesions was not significantly elevated in in situ zymography, which was our new attempt to detect the protease activity more precisely than conventional assays. This ineffective KLK activation was associated with impaired KLK7 secretion from lamellar granules and increased expression of LEKTI in AD. Such imbalances in protease-protease inhibitor interactions could lead to abnormal proteolysis of corneodesmosomes and compact hyperkeratosis. Upregulated expression of LEKTI might be a compensatory mechanism to prevent further barrier dysfunction in AD. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Lecithin-based microemulsions for targeted delivery of ceramide AP into the stratum corneum: formulation, characterizations, and in vitro release and penetration studies.

PubMed

Sahle, Fitsum F; Metz, Hendrik; Wohlrab, Johannes; Neubert, Reinhard H H

2013-02-01

To improve the solubility and penetration of Ceramide AP (CER [AP]) into the stratum corneum that potentially restores the barrier function of aged and affected skin. CER [AP] microemulsions (MEs) were formulated using lecithin, Miglyol® 812 (miglyol) and water-1,2 pentandiol (PeG) mixture as amphiphilic, oily and hydrophilic components, respectively. The nanostructure of the MEs was revealed using electrical conductivity, differential scanning calorimeter (DSC) and electron paramagnetic resonance (EPR) techniques. Photon correlation spectroscopy (PCS) was used to measure the sizes and shape of ME droplets. The release and penetration of the CER into the stratum corneum was investigated in vitro using a multi-layer membrane model. The MEs exhibited excellent thermodynamic stability (>2 years) and loading capacity (0.5% CER [AP]). The pseudo-ternary phase diagrams of the MEs were obtained and PCS results showed that the droplets are spherical in shape and bigger in size. In vitro investigations showed that the MEs exhibited excellent rate and extent of release and penetration. Stable lecithin-based CER [AP] MEs that significantly enhance the solubility and penetration of CER [AP] into the stratum corneum were developed. The MEs also have better properties than the previously reported polyglycerol fatty acid surfactant-based CER [AP] MEs.

Dew point effect of cooled hydrogel pads on human stratum corneum biosurface.

PubMed

Xhauflaire-Uhoda, Emmanuelle; Paquet, Philippe; Piérard, Gérald E

2008-01-01

Cooled hydrogel pads are used to prevent overheating effects of laser therapy. They do not induce cold injuries to the skin, but their more subtle physiological effects have not been thoroughly studied. To describe the changes in transepidermal water loss and electrometric properties of the skin surface following application of cooled hydrogel pads. Measurements were performed on normal forearm skin of 27 healthy volunteers and on freshly excised skin from abdominoplasty. LaserAid hydrogel pads cooled to 4 degrees C were placed for 15 min on the forearm skin. Measurements of transepidermal water loss (TEWL) and electrometric properties (Corneometer, Nova DPM 900) were performed before application and after removal of the cooled pads. A consistent increase in corneometer units, dermal phase meter (DPM) values and TEWL were recorded at removal of the cooled hydrogel pads. Both the in vivo and in vitro assessments brought similar information. The similar changes disclosed in vitro and in vivo suggest that a common physical process is operating in these conditions. The observed phenomenon is opposite to the predicted events given by the Arrhenius law probably because of the combination of cooling and occlusion by the pads. A dew point effect (air temperature at which relative humidity is maximal) is likely involved in the moisture content of the stratum corneum. Thus, the biological impact of using cooling hydrogel pads during laser therapy is different from the effect of a cryogenic spray cooling procedure. The better preservation of the water balance in the stratum corneum by the cooled hydrogel pads could have a beneficial esthetic effect on laser treated areas. (c) 2008 S. Karger AG, Basel.

Microbiome dynamics of human epidermis following skin barrier disruption

PubMed Central

2012-01-01

Background Recent advances in sequencing technologies have enabled metagenomic analyses of many human body sites. Several studies have catalogued the composition of bacterial communities of the surface of human skin, mostly under static conditions in healthy volunteers. Skin injury will disturb the cutaneous homeostasis of the host tissue and its commensal microbiota, but the dynamics of this process have not been studied before. Here we analyzed the microbiota of the surface layer and the deeper layers of the stratum corneum of normal skin, and we investigated the dynamics of recolonization of skin microbiota following skin barrier disruption by tape stripping as a model of superficial injury. Results We observed gender differences in microbiota composition and showed that bacteria are not uniformly distributed in the stratum corneum. Phylogenetic distance analysis was employed to follow microbiota development during recolonization of injured skin. Surprisingly, the developing neo-microbiome at day 14 was more similar to that of the deeper stratum corneum layers than to the initial surface microbiome. In addition, we also observed variation in the host response towards superficial injury as assessed by the induction of antimicrobial protein expression in epidermal keratinocytes. Conclusions We suggest that the microbiome of the deeper layers, rather than that of the superficial skin layer, may be regarded as the host indigenous microbiome. Characterization of the skin microbiome under dynamic conditions, and the ensuing response of the microbial community and host tissue, will shed further light on the complex interaction between resident bacteria and epidermis. PMID:23153041

Deposits from Creams Containing 20% (w/w) Urea and Suppression of Crystallization (Part 2): Novel Analytical Methods of Urea Accumulated in the Stratum Corneum by Tape stripping and Colorimetry.

PubMed

Goto, Norio; Morita, Yutaka; Terada, Katsuhide

2016-01-01

The transfer of urea from a urea formulation to the stratum corneum varies with the formulation base and form, and impacts the formulation's therapeutic effect. Consequently, determining the amount of urea transferred is essential for developing efficient formulations. This study assessed a simple method for measuring the amount of urea accumulated in the stratum corneum. Conventional methods rely on labeling urea used in the formulation with radiocarbon ((14)C) or other radioactive isotopes (RIs), retrieving the transferred urea from the stratum corneum by tape stripping, then quantitating the urea. The handling and use of RIs, however, is subject to legal regulation and can only be performed in sanctioned facilities, so methods employing RIs are neither simple nor convenient. We therefore developed a non-radiolabel method "tape stripping-colorimetry (T-C)" that combines tape stripping with colorimetry (urease-glutamate dehydrogenase (GLDH)) for the quantitative measurement of urea. Urea in the stratum corneum is collected by tape stripping and measured using urease-GLDH, which is commonly used to measure urea nitrogen in blood tests. The results indicate that accurate urea measurement by the T-C method requires the application of 1400 mg (on hairless rats) of a 20% urea solution on a 50 cm(2) (5×10 cm) area. Further, we determined the amount of urea accumulated in the stratum corneum using formulations with different urea concentrations, and the time course of urea accumulation from formulations differing in the rate of urea crystallization. We demonstrate that the T-C method is simple and convenient, with no need for (14)C or other RIs.

Differences in adhesion of Candida albicans 3153A cells exhibiting switch phenotypes to buccal epithelium and stratum corneum.

PubMed

Vargas, K; Wertz, P W; Drake, D; Morrow, B; Soll, D R

1994-04-01

Cells of the laboratory strain 3153A of Candida albicans can be stimulated to undergo high-frequency phenotypic switching by a low dose of UV. We have compared the adhesive properties of cells exhibiting the basic original smooth (o-smooth) phenotype and three switch phenotypes (star, irregular wrinkle, and revertant smooth) to buccal epithelium and stratum corneum. The generalized hierarchy of adhesion is as follows: o-smooth > irregular wrinkle > revertant smooth > star. This is the inverse of the hierarchy of the proportions of elongate hyphae formed by these phenotypes in culture. These results suggest that the differences in adhesion between o-smooth and the three switch phenotypes of strain 3153A reflect, at least in part, the level of interference due to the formation of elongate hyphae, which tend to cause clumping in suspension. No major differences in the levels of adhesion of cells of the different phenotypes between buccal epithelium and stratum corneum were observed. Results which demonstrate that buccal epithelium induces germination (hypha formation) by conditioning the medium are also presented.

The relationship between water loss, mechanical stress, and molecular structure of human stratum corneum ex vivo.

PubMed

Vyumvuhore, Raoul; Tfayli, Ali; Biniek, Krysta; Duplan, Hélène; Delalleau, Alexandre; Manfait, Michel; Dauskardt, Reinhold; Baillet-Guffroy, Arlette

2015-03-01

Proper hydration of the stratum corneum (SC) is important for maintaining skin's vital functions. Water loss causes development of drying stresses, which can be perceived as 'tightness', and plays an important role in dry skin damage processes. However, molecular structure modifications arising from water loss and the subsequent development of stress has not been established. We investigated the drying stress mechanism by studying, ex vivo, the behaviors of the SC components during water desorption from initially fully hydrated samples using Raman spectroscopy. Simultaneously, we measure the SC mechanical stress with a substrate curvature instrument. Very good correlations of water loss to the mechanical stress of the stratum corneum were obtained, and the latter was found to depend mainly on the unbound water fraction. In addition to that, the water loss is accompanied with an increase of lipids matrix compactness characterized by lower chain freedom, while protein structure showed an increase in amount of α-helices, a decline in α-sheets, and an increase in folding in the tertiary structure of keratin. The drying process of SC involves a complex interplay of water binding, molecular modifications, and mechanical stress. This article provides a better understanding of the molecular mechanism associated to SC mechanics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An In vitro Model for Bacterial Growth on Human Stratum Corneum.

PubMed

van der Krieken, Danique A; Ederveen, Thomas H A; van Hijum, Sacha A F T; Jansen, Patrick A M; Melchers, Willem J G; Scheepers, Paul T J; Schalkwijk, Joost; Zeeuwen, Patrick L J M

2016-11-02

The diversity and dynamics of the skin microbiome in health and disease have been studied recently, but adequate model systems to study skin microbiotas in vitro are largely lacking. We developed an in vitro system that mimics human stratum corneum, using human callus as substrate and nutrient source for bacterial growth. The growth of several commensal and pathogenic bacterial strains was measured for up to one week by counting colony-forming units or by quantitative PCR with strain-specific primers. Human skin pathogens were found to survive amidst a minimal microbiome consisting of 2 major skin commensals: Staphylococcus epidermidis and Propionibacterium acnes. In addition, complete microbiomes, taken from the backs of healthy volunteers, were inoculated and maintained using this system. This model may enable the modulation of skin microbiomes in vitro and allow testing of pathogens, biological agents and antibiotics in a medium-throughput format.

Assessing the Relationship between Vitamin D3 and Stratum Corneum Hydration for the Treatment of Xerotic Skin

PubMed Central

Russell, Meghan

2012-01-01

Vitamin D3 has been called the “sunshine” vitamin since the formation of vitamin D is mediated by exposure to sunlight. Vitamin D3 is linked to many health benefits, however serum levels of vitamin D3 have been decreasing over the last few decades and the lower levels of vitamin D3 may have consequences on normal physiology. We investigated the association between serum 25-hydroxyvitamin D (25(OH)D) levels and stratum corneum conductance as well as the effect of topical application of cholecalciferol (vitamin D3) on dry skin. Eighty three subjects were recruited and blood serum levels and skin conductance measurements were taken after a one week washout. A correlation was observed between vitamin D levels and skin moisture content, individuals with lower levels of vitamin D had lower average skin moisture. Subsequently, a 3-week split leg, randomized, vehicle controlled clinical study was conducted on a subset of 61 of the above individuals who were identified with non-sufficient vitamin D serum levels. Topical supplementation with cholecalciferol significantly increased measurements of skin moisturization and resulted in improvements in subjective clinical grading of dry skin. Taken together our finding suggest a relationship between serum vitamin D3 (25(OH)D) levels and hydration of the stratum corneum and further demonstrate the skin moisture benefit from topical application of vitamin D3. PMID:23112909

Assessing the relationship between vitamin D3 and stratum corneum hydration for the treatment of xerotic skin.

PubMed

Russell, Meghan

2012-09-01

Vitamin D(3) has been called the "sunshine" vitamin since the formation of vitamin D is mediated by exposure to sunlight. Vitamin D(3) is linked to many health benefits, however serum levels of vitamin D(3) have been decreasing over the last few decades and the lower levels of vitamin D(3) may have consequences on normal physiology. We investigated the association between serum 25-hydroxyvitamin D (25(OH)D) levels and stratum corneum conductance as well as the effect of topical application of cholecalciferol (vitamin D(3)) on dry skin. Eighty three subjects were recruited and blood serum levels and skin conductance measurements were taken after a one week washout. A correlation was observed between vitamin D levels and skin moisture content, individuals with lower levels of vitamin D had lower average skin moisture. Subsequently, a 3-week split leg, randomized, vehicle controlled clinical study was conducted on a subset of 61 of the above individuals who were identified with non-sufficient vitamin D serum levels. Topical supplementation with cholecalciferol significantly increased measurements of skin moisturization and resulted in improvements in subjective clinical grading of dry skin. Taken together our finding suggest a relationship between serum vitamin D(3) (25(OH)D) levels and hydration of the stratum corneum and further demonstrate the skin moisture benefit from topical application of vitamin D(3).

Preparation of a New Oligolamellar Stratum Corneum Lipid Model.

PubMed

Mueller, Josefin; Schroeter, Annett; Steitz, Roland; Trapp, Marcus; Neubert, Reinhard H H

2016-05-10

In this study, we present a preparation method for a new stratum corneum (SC) model system, which is closer to natural SC than the commonly used multilayer models. The complex setup of the native SC lipid matrix was mimicked by a ternary lipid mixture of ceramide [AP], cholesterol, and stearic acid. A spin coating procedure was applied to realize oligo-layered samples. The influence of lipid concentration, rotation speed, polyethylenimine, methanol content, cholesterol fraction, and annealing on the molecular arrangement of the new SC model was investigated by X-ray reflectivity measurements. The new oligo-SC model is closer to native SC in the total number of lipid membranes found between corneocytes. The reduction in thickness provides the opportunity to study the effects of drugs and/or hydrophilic penetration enhancers on the structure of SC in full detail by X-ray or neutron reflectivity. In addition, the oligo-lamellar systems allows one to infer not only the lamellar spacing, but also the total thickness of the oligo-SC model and changes thereof can be monitored. This improvement is most helpful for the understanding of transdermal drug administration on the nanoscale. The results are compared to the commonly used multilamellar lipid model systems and advantages and disadvantages of both models are discussed.

Cutaneous water loss and the development of the stratum corneum of nestling house sparrows (Passer domesticus) from desert and mesic environments.

PubMed

Muñoz-Garcia, Agustí; Williams, Joseph B

2011-01-01

Evaporation through the skin contributes to more than half of the total water loss in birds. Therefore, we expect the regulation of cutaneous water loss (CWL) to be crucial for birds, especially those that live in deserts, to maintain a normal state of hydration. Previous studies in adult birds showed that modifications of the lipid composition of the stratum corneum (SC), the outer layer of the epidermis, were associated with changes in rates of CWL. However, few studies have examined the ontogeny of CWL and the lipids of the SC in nestling birds. In this study, we measured CWL and the lipid composition of the SC during development of nestlings from two populations of house sparrows, one from the deserts of Saudi Arabia and the other from mesic Ohio. We found that desert and mesic nestlings followed different developmental trajectories for CWL. Desert nestlings seemed to make a more frugal use of water than did mesic nestlings. To regulate CWL, nestlings appeared to modify the lipid composition of the SC during ontogeny. Our results also suggest a tighter regulation of CWL in desert nestlings, presumably as a result of the stronger selection pressures to which nestlings are exposed in deserts.

Recent advances in X-ray microanalysis in dermatology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forslind, B.; Grundin, T.G.; Lindberg, M.

1985-01-01

Electron microprobe and proton microprobe X-ray analysis can be used in several areas of dermatological research. With a proton probe, the distribution of trace elements in human hair can be determined. Electron microprobe analysis on freeze-dried cryosections of guinea-pig and human epidermis shows a marked gradient of Na, P and K over the stratum granulosum. In sections of freeze-substituted human skin this gradient is less steep. This difference is likely to be due to a decrease in water content of the epidermis towards the stratum corneum. Electron microprobe analysis of the epidermis can, for analysis of trace elements, be complementedmore » by the proton microprobe. Quantitative agreement between the two techniques can be obtained by the use of a standard. Proton microprobe analysis was used to determine the distribution of Ni or Cr in human epidermis exposed to nickel or chromate ions. Possible differences in water content between the stratum corneum of patients with atopic eczema and normal stratum corneum was investigated in skin freeze-substituted with Br-doped resin. No significant differences were observed.« less

Electroperturbation of human stratum corneum fine structure by high voltage pulses: a freeze-fracture electron microscopy and differential thermal analysis study.

PubMed

Jadoul, A; Tanojo, H; Préat, V; Bouwstra, J A; Spies, F; Boddé, H E

1998-08-01

Application of high voltage pulses (HVP) to the skin has been shown to promote the transdermal drug delivery by a mechanism involving skin electroporation. The aim of this study was to detect potential changes in lipid phase and ultrastructure induced in human stratum corneum by various HVP protocols, using differential thermal analysis and freeze-fracture electron microscopy. Due to the time involved between the moment the electric field is switched off and the analysis, only "secondary" phenomena rather than primary events could be observed. A decrease in enthalpies for the phase transitions observed at 70 degrees C and 85 degrees C was detected by differential thermal analysis after HVP treatment. No changes in transition temperature could be seen. The freeze-fracture electron microscopy study revealed a dramatic perturbation of the lamellar ordering of the intercellular lipid after application of HVP. Most of the planes displayed rough surfaces. The lipid lamellae exhibited rounded off steps or a vanished stepwise order. There was no evidence for perturbation of the corneocytes content. In conclusion, the freeze-fracture electron microscopy and differential thermal analysis studies suggest that HVP application induces a general perturbation of the stratum corneum lipid ultrastructure.

Skin permeation and antioxidant efficacy of topically applied resveratrol.

PubMed

Alonso, Cristina; Martí, M; Barba, C; Carrer, V; Rubio, L; Coderch, L

2017-08-01

The permeation of resveratrol was assessed by in vitro and in vivo experiments 24 h after topical administration. The in vitro profile of resveratrol was assessed by Raman spectroscopy. Human skin permeation was analysed in vivo by the tape stripping method with the progressive removal of the stratum corneum layers using adhesive tape strips. Moreover, the free radical scavenging activity of resveratrol after its topical application was determined using the DPPH assay. The Raman spectra indicated that the topically applied resveratrol penetrates deep into the skin. The results showed high amounts of resveratrol in the different stratum corneum layers close to the surface and a constant lower amount in the upper layers of the viable epidermis. The concentration of resveratrol present in the outermost stratum corneum layers was obtained by tape stripping after in vivo application. The results demonstrated that resveratrol mainly remained in the human stratum corneum layers. After topical application, resveratrol maintained its antiradical activity. The antioxidant efficacy of the compound was higher in the inner layers of the stratum corneum. As these results have demonstrated, topically applied resveratrol reinforces the antioxidant system of the stratum corneum and provides an efficient means of increasing the tissue levels of antioxidants in the human epidermis.

Hydration effects on the barrier function of stratum corneum lipids: Raman analysis of ceramides 2, III and 5.

PubMed

Tfayli, Ali; Jamal, Dima; Vyumvuhore, Raoul; Manfait, Michel; Baillet-Guffroy, Arlette

2013-11-07

The stratum corneum is the outermost layer of the skin; its barrier function is highly dependent on the composition and the structure as well as the organization of lipids in its extracellular matrix. Ceramides, free fatty acids and cholesterol represent the major lipid classes present in this matrix. They play an important role in maintaining the normal hydration levels required for the normal physiological function. Despite the advancement in the understanding of the structure, composition and the function of the stratum corneum (SC), the concern of "dry skin" remains important in dermatology and care research. Most studies focus on the quantification of water in the skin using different techniques including Raman spectroscopy, while the studies that investigate the effect of hydration on the quality of the barrier function of the skin are limited. Raman spectroscopy provides structural, conformational and organizational information that could help elucidate the effect of hydration on the barrier function of the skin. In order to assess the effect of relative humidity on the lipid barrier function; we used Raman spectroscopy to follow-up the evolution of the conformation and the organization of three synthetic ceramides (CER) differing from each other by the nature of their polar heads (sphingosine, phytosphingosine and α hydroxyl sphingosine), CER 2, III and 5 respectively. CER III and 5 showed a more compact and ordered organization with stronger polar interactions at intermediate relative humidity values, while CER 2 showed opposite tendencies to those observed with CER III and 5.

Effect of topically applied dexpanthenol on epidermal barrier function and stratum corneum hydration. Results of a human in vivo study.

PubMed

Gehring, W; Gloor, M

2000-07-01

In a randomized, double-blind, placebo-controlled study the effect of topical dexpanthenol (CAS 81-13-0) formulated in two different lipophilic vehicles on epidermal barrier function in vivo was carried out. Seven days' treatment with dexpanthenol improved stratum corneum hydration and reduced transepidermal water loss. Active treatment was statistically different from the vehicle control on both measures. Our results suggest that topical dexpanthenol formulated in either lipophilic vehicle stabilizes the skin barrier function.

Combined LC/MS-platform for analysis of all major stratum corneum lipids, and the profiling of skin substitutes.

PubMed

van Smeden, Jeroen; Boiten, Walter A; Hankemeier, Thomas; Rissmann, Robert; Bouwstra, Joke A; Vreeken, Rob J

2014-01-01

Ceramides (CERs), cholesterol, and free fatty acids (FFAs) are the main lipid classes in human stratum corneum (SC, outermost skin layer), but no studies report on the detailed analysis of these classes in a single platform. The primary aims of this study were to 1) develop an LC/MS method for (semi-)quantitative analysis of all main lipid classes present in human SC; and 2) use this method to study in detail the lipid profiles of human skin substitutes and compare them to human SC lipids. By applying two injections of 10μl, the developed method detects all major SC lipids using RPLC and negative ion mode APCI-MS for detection of FFAs, and NPLC using positive ion mode APCI-MS to analyze CERs and cholesterol. Validation showed this lipid platform to be robust, reproducible, sensitive, and fast. The method was successfully applied on ex vivo human SC, human SC obtained from tape strips and human skin substitutes (porcine SC and human skin equivalents). In conjunction with FFA profiles, clear differences in CER profiles were observed between these different SC sources. Human skin equivalents more closely mimic the lipid composition of human stratum corneum than porcine skin does, although noticeable differences are still present. These differences gave biologically relevant information on some of the enzymes that are probably involved in SC lipid processing. For future research, this provides an excellent method for (semi-)quantitative, 'high-throughput' profiling of SC lipids and can be used to advance the understanding of skin lipids and the biological processes involved. © 2013.

Brewster Angle Microscopy Study of Model Stratum Corneum Lipid Monolayers at the Air-Water Interface

NASA Astrophysics Data System (ADS)

Adams, Ellen; Champagne, Alex; William, Joseph; Allen, Heather

2012-04-01

As the first and last barrier in the body, the stratum corneum (SC) is essential to life. Understanding the interactions and organization of lipids within the SC provides insight into essential physiological processes, including water loss prevention and the adsorption of substances from the environment. Langmuir monolayers have long been used to study complex systems, such as biological membranes and marine aerosols, due to their ability to shed light on intermolecular interactions. In this study, lipid mixtures with varying cholesterol and cerebroside ratios were investigated at the air/water interface. Surface tension measurements along with Brewster angle microscopy (BAM) images were used to examine the lipid phase transitions. Results indicate that cholesterol and cerebrosides form miscible monolayers, exhibiting ideal behavior. BAM images of a singular, uniform collapse phase also suggest formation of a miscible monolayer.

Developmental plasticity of cutaneous water loss and lipid composition in stratum corneum of desert and mesic nestling house sparrows

PubMed Central

Muñoz-Garcia, Agustí; Williams, Joseph B.

2008-01-01

Intercellular lipids of the stratum corneum (SC), the outer layer of the epidermis, form a barrier to water vapor diffusion through the skin. Previously, we measured cutaneous water loss (CWL) and lipid composition of the SC of adult house sparrows from two populations, one living in the deserts of Saudi Arabia and another living in mesic Ohio. Adult desert house sparrows had a lower CWL, a lower proportion of free fatty acids, and a higher proportion of ceramides and cerebrosides in the SC compared with mesic sparrows. In this study, we investigated developmental plasticity of CWL and lipid composition of the SC in desert and mesic nestling house sparrows reared in low and high humidity and compared our results with previous work on adults. We measured CWL of nestlings and analyzed the lipid composition of the SC using thin-layer chromatography. We showed that nestling house sparrows from both localities had higher CWL than adults in their natural environment, a result of major modifications of the lipid composition of the SC. The expression of plasticity in CWL seems to be a response to opposed selection pressures, thermoregulation and water conservation, at different life stages, on which regulation of CWL plays a crucial role. Desert nestlings showed a greater degree of plasticity in CWL and lipid composition of the SC than did mesic nestlings, a finding consistent with the idea that organisms exposed to more environmental stress ought to be more plastic than individuals living in more benign environments. PMID:18838693

Developmental plasticity of cutaneous water loss and lipid composition in stratum corneum of desert and mesic nestling house sparrows.

PubMed

Muñoz-Garcia, Agustí; Williams, Joseph B

2008-10-07

Intercellular lipids of the stratum corneum (SC), the outer layer of the epidermis, form a barrier to water vapor diffusion through the skin. Previously, we measured cutaneous water loss (CWL) and lipid composition of the SC of adult house sparrows from two populations, one living in the deserts of Saudi Arabia and another living in mesic Ohio. Adult desert house sparrows had a lower CWL, a lower proportion of free fatty acids, and a higher proportion of ceramides and cerebrosides in the SC compared with mesic sparrows. In this study, we investigated developmental plasticity of CWL and lipid composition of the SC in desert and mesic nestling house sparrows reared in low and high humidity and compared our results with previous work on adults. We measured CWL of nestlings and analyzed the lipid composition of the SC using thin-layer chromatography. We showed that nestling house sparrows from both localities had higher CWL than adults in their natural environment, a result of major modifications of the lipid composition of the SC. The expression of plasticity in CWL seems to be a response to opposed selection pressures, thermoregulation and water conservation, at different life stages, on which regulation of CWL plays a crucial role. Desert nestlings showed a greater degree of plasticity in CWL and lipid composition of the SC than did mesic nestlings, a finding consistent with the idea that organisms exposed to more environmental stress ought to be more plastic than individuals living in more benign environments.

Melanin fate in the human epidermis: a reassessment of how best to detect and analyse histologically.

PubMed

Joly-Tonetti, Nicolas; Wibawa, Judata I D; Bell, Mike; Tobin, Desmond

2016-07-01

Melanin is the predominant pigment responsible for skin colour and is synthesized by the melanocyte in the basal layer of the epidermis and then transferred to surrounding keratinocytes. Despite its optical properties, melanin is barely detectable in unstained sections of human epidermis. However, identification and localization of melanin is of importance for the study of skin pigmentation in health and disease. Current methods for the histologic quantification of melanin are suboptimal and are associated with significant risk of misinterpretation. The aim of this study was to reassess the existing literature and to develop a more effective histological method of melanin quantification in human skin. Moreover, we confirm that Warthin-Starry (WS) stain provides a much more sensitive and more specific melanin detection method than the commonplace Fontana-Masson (FM) stain. For example, WS staining sensitivity allowed the visualization of melanin even in very pale Caucasian skin that was missed by FM or Von Kossa (VK) stains. From our reassessment of the histology-related literature, we conclude that so-called melanin dust is most likely an artifact of discoloration due to non-specific silver deposition in the stratum corneum. Unlike FM and VK, WS was not associated with this non-specific stratum corneum darkening, misinterpreted previously as 'degraded' melanin. Finally, WS melanin particle counts were largely similar to previously reported manual counts by transmission electron microscopy, in contrast to both FM and VK. Together these findings allow us to propose a new histology/Image J-informed method for the accurate and precise quantification of epidermal melanin in skin. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of silicone gel sheet on the stratum corneum hydration.

PubMed

Suetak, T; Sasai, S; Zhen, Y X; Tagami, H

2000-09-01

Various groups have reported the efficacy of treatment with topical silicone gel sheet (SGS) for keloids and hypertrophic scars. Because its hydrating effect on the stratum corneum (SC) has been suggested as a mechanism underlying its therapeutic effectiveness, we evaluated it by comparing it with simple plastic film occlusion. With biophysical instruments we assessed the water content of the skin surface as well as its water evaporation on the flexor aspects of bilateral forearms of 10 healthy volunteers for 30min after removal of dressings of SGS or a plastic film that were applied either for 1 day or for 7 days. Occlusion with SGS or plastic film induced hydration of the skin surface, which was followed by an initial quick and later slow process of dehydration when the skin was exposed to the ambient atmosphere. The magnitude of the increase in hydration induced by SGS was always smaller than that of the plastic film occlusion and, unlike the latter treatment, hydration became less with repetition of SGS treatment. On day 7, the SC hydration quickly reduced to the level of non-treated control skin after removal of the dressings. An in vivo test demonstrated that the water-holding capacity of the SC normalised after 7 days of SGS treatment. SGS probably produces a favourable condition for the skin by protecting it from various environmental stimuli, while keeping the SC in an adequately but not over-hydrated condition.

In vivo confocal Raman spectroscopic analysis of the effects of IR radiation in the stratum corneum of human skin (Conference Presentation)

NASA Astrophysics Data System (ADS)

Rajasekaran, Ramu; Bergamo Lopes, Monica; Magrini, Taciana D.; Figueira Lopes Cançado, Ana Clara; Abrahao Martin, Airton

2017-02-01

Stratum Corneum is the outer covering of the body, which serves as a barrier to infection. The composition of the skin changes withexternal environmental factors, such as temperature, sun irradiation, air pollutants, chemical hazards, as well as other factors.Solar radiation,especially IR radiation is being used as medicine for wound healing processes, in cosmetology, in physiotherapy and warming of muscles. Also, it was reported that the IR radiation produces free radicals and the excess production of free radicals causes irreversible damages. It has been reported that heat may be transmitted by IR radiation, which results in raised skin temperature and the chronic heat exposure of human skin may cause alterations. Erythema igne is one such disease known to be caused by chronic heat exposure. Many techniques have been adopted for monitoring the changes in the skin, which includes the tape stripping and biopsy as the primary methodology. However, these in vitro techniques are invasive, time consuming, and may not provide the actual information as in in vivo conditions. Confocal Raman spectroscopy,which is non-invasive and real time was considered as a potential tool for the in vivo analysis of the distribution and characteristics of different metabolic conditions and their variations of the skin. In this regard, we aimed at in vivo characterization of the IR induced changes in the stratum corneum of human volunteers. The results of Raman spectral signatures with respect to the control and IR exposed skin will be discussed.

Soft epidermis of a scaleless snake lacks beta-keratin.

PubMed

Toni, M; Alibardi, L

2007-01-01

Beta-keratins are responsible for the mechanical resistance of scales in reptiles. In a scaleless crotalus snake (Crotalus atrox), large areas of the skin are completely devoid of scales, and the skin appears delicate and wrinkled. The epidermis of this snake has been assessed for the presence of beta-keratin by immunocytochemistry and immunoblotting using an antibody against chicken scale beta-keratin. This antibody recognizes beta-keratins in normal snake scales with molecular weights of 15-18 kDa and isoelectric points at 6.8, 7.5, 8.3 and 9.4. This indicates that beta-keratins of the stratum corneum are mainly basic proteins, so may interact with cytokeratins of the epidermis, most of which appear acidic (isoelectric points 4.5-5.5). A beta-layer and beta-keratin immunoreactivity are completely absent in moults of the scaleless mutant, and the corneous layer comprises a multi-layered alpha-layer covered by a flat oberhautchen. In conclusion, the present study shows that a lack of beta-keratins is correlated with the loss of scales and mechanical protection in the skin of this mutant snake.

Inhibition of apoptosis signal-regulating kinase 1 alters the wound epidermis and enhances auricular cartilage regeneration

PubMed Central

Zhang, Qian-Shi; Kurpad, Deepa S.; Mahoney, My G.; Steinbeck, Marla J.

2017-01-01

Why regeneration does not occur in mammals remains elusive. In lower vertebrates, epimorphic regeneration of the limb is directed by the wound epidermis, which controls blastema formation to promote regrowth of the appendage. Herein, we report that knockout (KO) or inhibition of Apoptosis Signal-regulated Kinase-1 (ASK1), also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5), after full thickness ear punch in mice prolongs keratinocyte activation within the wound epidermis and promotes regeneration of auricular cartilage. Histological analysis showed the ASK1 KO ears displayed enhanced protein markers associated with blastema formation, hole closure and regeneration of auricular cartilage. At seven days after punch, the wound epidermis morphology was markedly different in the KO, showing a thickened stratum corneum with rounded cell morphology and a reduction of both the granular cell layer and decreased expression of filament aggregating protein. In addition, cytokeratin 6 was expressed in the stratum spinosum and granulosum. Topical application of inhibitors of ASK1 (NQDI-1), the upstream ASK1 activator, calcium activated mitogen kinase 2 (KN93), or the downstream target, c-Jun N-terminal kinase (SP600125) also resulted in enhanced regeneration; whereas inhibition of the other downstream target, the p38 α/β isoforms, (SB203580) had no effect. The results of this investigation indicate ASK1 inhibition prolongs keratinocyte and blastemal cell activation leading to ear regeneration. PMID:29045420

Inhibition of apoptosis signal-regulating kinase 1 alters the wound epidermis and enhances auricular cartilage regeneration.

PubMed

Zhang, Qian-Shi; Kurpad, Deepa S; Mahoney, My G; Steinbeck, Marla J; Freeman, Theresa A

2017-01-01

Why regeneration does not occur in mammals remains elusive. In lower vertebrates, epimorphic regeneration of the limb is directed by the wound epidermis, which controls blastema formation to promote regrowth of the appendage. Herein, we report that knockout (KO) or inhibition of Apoptosis Signal-regulated Kinase-1 (ASK1), also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5), after full thickness ear punch in mice prolongs keratinocyte activation within the wound epidermis and promotes regeneration of auricular cartilage. Histological analysis showed the ASK1 KO ears displayed enhanced protein markers associated with blastema formation, hole closure and regeneration of auricular cartilage. At seven days after punch, the wound epidermis morphology was markedly different in the KO, showing a thickened stratum corneum with rounded cell morphology and a reduction of both the granular cell layer and decreased expression of filament aggregating protein. In addition, cytokeratin 6 was expressed in the stratum spinosum and granulosum. Topical application of inhibitors of ASK1 (NQDI-1), the upstream ASK1 activator, calcium activated mitogen kinase 2 (KN93), or the downstream target, c-Jun N-terminal kinase (SP600125) also resulted in enhanced regeneration; whereas inhibition of the other downstream target, the p38 α/β isoforms, (SB203580) had no effect. The results of this investigation indicate ASK1 inhibition prolongs keratinocyte and blastemal cell activation leading to ear regeneration.

Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate.

PubMed

De Jongh, Cindy M; Verberk, Maarten M; Withagen, Carien E T; Jacobs, John J L; Rustemeyer, Thomas; Kezic, Sanja

2006-06-01

Little is known about cytokines involved in chronic irritant contact dermatitis. Individual cytokine profiles might explain at least part of the differences in the individual response to irritation. Our objective was to investigate the relation between baseline stratum corneum (SC) cytokine levels and the skin response to a single and a repeated irritation test. This study also aimed to determine changes in SC cytokine levels after repeated irritation. Transepidermal water loss (TEWL) and erythema were measured in 20 volunteers after single 24-hr exposure to 1% sodium lauryl sulfate (SLS), and during and after repeated exposure to 0.1% SLS over a 3-week period. SC cytokine levels were measured from an unexposed skin site and from the repeatedly exposed site. Interleukin (IL)-1alpha decreased by 30% after repeated exposure, while IL-1RA increased 10-fold and IL-8 increased fourfold. Baseline IL-1RA and IL-8 values were predictors of TEWL and erythema after single exposure (r = 0.55-0.61). 6 subjects showed barrier recovery during repeated exposure. Baseline IL-1RA and IL-8 levels are likely to be indicators of higher skin irritability after single exposure to SLS. Barrier repair in some of the subjects might explain the lack of agreement between the TEWL response after single and repeated irritation.

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

PubMed

Visscher, Marty O; Robinson, Marisa; Fugit, Benetta; Rosenberg, Richard J; Hoath, Steven B; Randall Wickett, R

2011-03-01

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.

Cutaneous water loss and covalently bound lipids of the stratum corneum in nestling house sparrows (Passer domesticus L.) from desert and mesic habitats.

PubMed

Clement, Michelle E; Muñoz-Garcia, Agustí; Williams, Joseph B

2012-04-01

Lipids of the stratum corneum (SC), the outer layer of the epidermis of birds and mammals, provide a barrier to water vapor diffusion through the skin. The SC of birds consists of flat dead cells, called corneocytes, and two lipid compartments: an intercellular matrix and a monolayer of covalently bound lipids (CBLs) attached to the outer surface of the corneocytes. We previously found two classes of sphingolipids, ceramides and cerebrosides, covalently bound to corneocytes in the SC of house sparrows (Passer domesticus L.); these lipids were associated with cutaneous water loss (CWL). In this study, we collected adult and nestling house sparrows from Ohio and nestlings from Saudi Arabia, acclimated them to either high or low humidity, and measured their rates of CWL. We also measured CWL for natural populations of nestlings from Ohio and Saudi Arabia, beginning when chicks were 2 days old until they fledged. We then evaluated the composition of the CBLs of the SC of sparrows using thin layer chromatography. We found that adult house sparrows had a greater diversity of CBLs in their SC than previously described. During ontogeny, nestling sparrows increased the amount of CBLs and developed their CBLs differently, depending on their habitat. Acclimating nestlings to different humidity regimes did not alter the ontogeny of the CBLs, suggesting that these lipids represent a fundamental component of SC organization that does not respond to short-term environmental change.

The Structure of the Human Vaginal Stratum Corneum and its Role in Immune Defense

PubMed Central

Anderson, Deborah J.; Marathe, Jai; Pudney, Jeffrey

2014-01-01

The superficial layers of the human vaginal epithelium, which form an interface between host and environment, are comprised of dead flattened cells that have undergone a terminal cell differentiation program called cornification. This entails extrusion of nuclei and intercellular organelles, and the depletion of functional DNA and RNA precluding the synthesis of new proteins. As a consequence, the terminally differentiated cells do not maintain robust intercellular junctions and have a diminished capacity to actively respond to microbial exposure, yet the vaginal stratum corneum (SC) mounts an effective defense against invasive microbial infections. The vaginal SC in reproductive aged women is comprised of loosely connected glycogen-filled cells which are permeable to bacterial and viral microbes as well as molecular and cellular mediators of immune defense. We propose here that the vaginal SC provides a unique microenvironment that maintains vaginal health by fostering endogenous lactobacillii and retaining critical mediators of acquired and innate immunity. A better understanding of the molecular and physicochemical properties of the vaginal SC could promote the design of more effective topical drugs and microbicides. PMID:24661416

Stratum Corneum Lipids: Their Role for the Skin Barrier Function in Healthy Subjects and Atopic Dermatitis Patients.

PubMed

van Smeden, Jeroen; Bouwstra, Joke A

2016-01-01

Human skin acts as a primary barrier between the body and its environment. Crucial for this skin barrier function is the lipid matrix in the outermost layer of the skin, the stratum corneum (SC). Two of its functions are (1) to prevent excessive water loss through the epidermis and (2) to avoid that compounds from the environment permeate into the viable epidermal and dermal layers and thereby provoke an immune response. The composition of the SC lipid matrix is dominated by three lipid classes: cholesterol, free fatty acids and ceramides. These lipids adopt a highly ordered, 3-dimensional structure of stacked densely packed lipid layers (lipid lamellae): the lateral and lamellar lipid organization. The way in which these lipids are ordered depends on the composition of the lipids. One very common skin disease in which the SC lipid barrier is affected is atopic dermatitis (AD). This review addresses the SC lipid composition and organization in healthy skin, and elaborates on how these parameters are changed in lesional and nonlesional skin of AD patients. Concerning the lipid composition, the changes in the three main lipid classes and the importance of the carbon chain lengths of the lipids are discussed. In addition, this review addresses how these changes in lipid composition induce changes in lipid organization and subsequently correlate with an impaired skin barrier function in both lesional and nonlesional skin of these patients. Furthermore, the effect of filaggrin and mutations in the filaggrin gene on the SC lipid composition is critically discussed. Also, the breakdown products of filaggrin, the natural moisturizing factor molecules and its relation to SC-pH is described. Finally, the paper discusses some major changes in epidermal lipid biosynthesis in patients with AD and other related skin diseases, and how inflammation has a deteriorating effect on the SC lipids and SC biosynthesis. The review ends with perspectives on future studies in relation to

In vivo multiphoton imaging of human skin: assessment of topical corticosteroid-induced epidermis atrophy and depigmentation

NASA Astrophysics Data System (ADS)

Ait El Madani, Hassan; Tancrède-Bohin, Emmanuelle; Bensussan, Armand; Colonna, Anne; Dupuy, Alain; Bagot, Martine; Pena, Ana-Maria

2012-02-01

Multiphoton microscopy has emerged in the past decade as a promising tool for noninvasive skin imaging. Our aim was to evaluate the potential of multiphoton microscopy to detect topical corticosteroids side effects within the epidermis and to provide new insights into their dynamics. Healthy volunteers were topically treated with clobetasol propionate on a small region of their forearms under overnight occlusion for three weeks. The treated region of each patient was investigated at D0, D7, D15, D22 (end of the treatment), and D60. Our study shows that multiphoton microscopy allows for the detection of corticoid-induced epidermis modifications: thinning of stratum corneum compactum and epidermis, decrease of keratinocytes size, and changes in their morphology from D7 to D22. We also show that multiphoton microscopy enables in vivo three-dimensional (3-D) quantitative assessment of melanin content. We observe that melanin density decreases during treatment and almost completely disappears at D22. Moreover, these alterations are reversible as they are no longer present at D60. Our study demonstrates that multiphoton microscopy is a convenient and powerful tool for noninvasive 3-D dynamical studies of skin integrity and pigmentation.

Two dimensional finite element modelling for dynamic water diffusion through stratum corneum.

PubMed

Xiao, Perry; Imhof, Robert E

2012-10-01

Solvents penetration through in vivo human stratum corneum (SC) has always been an interesting research area for trans-dermal drug delivery studies, and the importance of intercellular routes (diffuse in between corneocytes) and transcellular routes (diffuse through corneocytes) during diffusion is often debatable. In this paper, we have developed a two dimensional finite element model to simulate the dynamic water diffusion through the SC. It is based on the brick-and-mortar model, with brick represents corneocytes and mortar represents lipids, respectively. It simulates the dynamic water diffusion process through the SC from pre-defined initial conditions and boundary conditions. Although the simulation is based on water diffusions, the principles can also be applied to the diffusions of other topical applied substances. The simulation results show that both intercellular routes and transcellular routes are important for water diffusion. Although intercellular routes have higher flux rates, most of the water still diffuse through transcellular routes because of the high cross area ratio of corneocytes and lipids. The diffusion water flux, or trans-epidermal water loss (TEWL), is reversely proportional to corneocyte size, i.e. the larger the corneocyte size, the lower the TEWL, and vice versa. There is also an effect of the SC thickness, external air conditions and diffusion coefficients on the water diffusion through SC on the resulting TEWL. Copyright © 2012 Elsevier B.V. All rights reserved.

Vehicle effects on human stratum corneum absorption and skin penetration.

PubMed

Zhang, Alissa; Jung, Eui-Chang; Zhu, Hanjiang; Zou, Ying; Hui, Xiaoying; Maibach, Howard

2017-05-01

This study evaluated the effects of three vehicles-ethanol (EtOH), isopropyl alcohol (IPA), and isopropyl myristate (IPM)-on stratum corneum (SC) absorption and diffusion of the [ 14 C]-model compounds benzoic acid and butenafine hydrochloride to better understand the transport pathways of chemicals passing through and resident in SC. Following application of topical formulations to human dermatomed skin for 30 min, penetration flux was observed for 24 h post dosing, using an in vitro flow-through skin diffusion system. Skin absorption and penetration was compared to the chemical-SC (intact, delipidized, or SC lipid film) binding levels. A significant vehicle effect was observed for chemical skin penetration and SC absorption. IPA resulted in the greatest levels of intact SC/SC lipid absorption, skin penetration, and total skin absorption/penetration of benzoic acid, followed by IPM and EtOH, respectively. For intact SC absorption and total skin absorption/penetration of butenafine, the vehicle that demonstrated the highest level of sorption/penetration was EtOH, followed by IPA and IPM, respectively. The percent doses of butenafine that were absorbed in SC lipid film and penetrated through skin in 24 h were greatest for IPA, followed by EtOH and IPM, respectively. The vehicle effect was consistent between intact SC absorption and total chemical skin absorption and penetration, as well as SC lipid absorption and chemical penetration through skin, suggesting intercellular transport as a main pathway of skin penetration for model chemicals. These results suggest the potential to predict vehicle effects on skin permeability with simple SC absorption assays. As decontamination was applied 30 min after chemical exposure, significant vehicle effects on chemical SC partitioning and percutaneous penetration also suggest that skin decontamination efficiency is vehicle dependent, and an effective decontamination method should act on chemical solutes in the lipid domain.

Emulsion-Based Intradermal Delivery of Melittin in Rats.

PubMed

Han, Sang Mi; Kim, Se Gun; Pak, Sok Cheon

2017-05-19

Bee venom (BV) has long been used as a traditional medicine. The aim of the present study was to formulate a BV emulsion with good rheological properties for dermal application and investigate the effect of formulation on the permeation of melittin through dermatomed rat skin. A formulated emulsion containing 1% ( w / v ) BV was prepared. The emulsion was compared with distilled water (DW) and 25% ( w / v ) N -methyl-2-pyrrolidone (NMP) in DW. Permeation of melittin from aqueous solution through the dermatomed murine skin was evaluated using the Franz diffusion cells. Samples of receptor cells withdrawn at pre-determined time intervals were measured for melittin amount. After the permeation study, the same skin was used for melittin extraction. In addition, a known amount of melittin (5 μg/mL) was added to stratum corneum, epidermis, and dermis of the rat skin, and the amount of melittin was measured at pre-determined time points. The measurement of melittin from all samples was done with HPLC-MS/MS. No melittin was detected in the receptor phase at all time points in emulsion, DW, or NMP groups. When the amount of melittin was further analyzed in stratum corneum, epidermis, and dermis from the permeation study, melittin was still not detected. In an additional experiment, the amount of melittin added to all skin matrices was corrected against the amount of melittin recovered. While the total amount of melittin was retained in the stratum corneum, less than 10% of melittin remained in epidermis and dermis within 15 and 30 min, respectively. Skin microporation with BV emulsion facilitates the penetration of melittin across the stratum corneum into epidermis and dermis, where emulsified melittin could have been metabolized by locally-occurring enzymes.

Skin hydration: interplay between molecular dynamics, structure and water uptake in the stratum corneum.

PubMed

Mojumdar, Enamul Haque; Pham, Quoc Dat; Topgaard, Daniel; Sparr, Emma

2017-11-16

Hydration is a key aspect of the skin that influences its physical and mechanical properties. Here, we investigate the interplay between molecular and macroscopic properties of the outer skin layer - the stratum corneum (SC) and how this varies with hydration. It is shown that hydration leads to changes in the molecular arrangement of the peptides in the keratin filaments as well as dynamics of C-H bond reorientation of amino acids in the protruding terminals of keratin protein within the SC. The changes in molecular structure and dynamics occur at a threshold hydration corresponding to ca. 85% relative humidity (RH). The abrupt changes in SC molecular properties coincide with changes in SC macroscopic swelling properties as well as mechanical properties in the SC. The flexible terminals at the solid keratin filaments can be compared to flexible polymer brushes in colloidal systems, creating long-range repulsion and extensive swelling in water. We further show that the addition of urea to the SC at reduced RH leads to similar molecular and macroscopic responses as the increase in RH for SC without urea. The findings provide new molecular insights to deepen the understanding of how intermediate filament organization responds to changes in the surrounding environment.

Terahertz wave techniques using a metal mesh for evaluating the components of the stratum corneum.

PubMed

Mizukoshi, Koji; Yonekura, Kazuki; Ogura, Hidehiro; Guan, Yu; Kawase, Kodo

2013-02-01

Terahertz waves are located in the region of the spectrum between milliwaves and infrared. We analyzed the feasibility of terahertz spectroscopy to inspect the compositional variations of the stratum corneum (SC). We used a terahertz time-domain spectroscopy system with the metal mesh technique. To investigate whether terahertz can inspect compositional variation of SC, we measured the terahertz frequency spectra of the SC sheet that was treated with chloroform-methanol, lipid mixture, a denaturation agent, and heating with hot air. The chloroform-methanol treatment of the SC shifted the dip position, which represents a convex downward shape of the spectra, to a higher frequency. This dip shift was reversed to an untreated position by the dose-dependent application of a lipid mixture. The heating treatment of the SC shifted the dip position to a higher frequency. The same dip shift was also induced by the application of a denaturation agent to the SC. The technique using terahertz waves with a metal mesh is effective because of its simplicity and its high degree of accuracy in detecting the amount of lipid and the protein conformation state. © 2012 John Wiley & Sons A/S.

Influence of DMPS on the water retention capacity of electroporated stratum corneum: ATR-FTIR study.

PubMed

Sckolnick, Maria; Hui, Sek-Wen; Sen, Arindam

2008-02-28

Anionic lipids like phosphatidylserine are known to significantly enhance electroporation mediated transepidermal transport of polar solutes of molecular weights up to 10kDa. The underlying mechanism of the effect of anionic lipids on transdermal transport is not fully understood. The main barrier to transdermal transport lies within the intercellular lipid matrix (ILM) of the stratum corneum (SC) and our previous studies indicate that dimyristoyl phosphatidylserine (DMPS) can perturb the packing of this lipid matrix. Here we report on our investigation on water retention in the SC following electroporation in the presence and the absence of DMPS. The water content in the outer most layers of the SC of full thickness porcine skin was determined using ATR-FTIR-spectroscopy. The results show that in the presence of DMPS, the SC remains in a state of enhanced hydration for longer periods after electroporation. This increase in water retention in the SC by DMPS is likely to play an important role in trans-epidermal transport, since improved hydration of the skin barrier can be expected to increase the partitioning of polar solutes and possibly the permeability.

Comparative distribution of sulphur, thiols and disulphides in the porcine stratum corneum.

PubMed

Meyer, W; Zschemisch, N H; Lehmann, H; Busche, R; Kunz, U

2005-01-01

Biochemical, histochemical and cytochemical analyses were used to determine the sulphur contents and the thiol and disulphide distribution in the stratum corneum (SC) of the wild boar (WB), a large domestic pig breed (DP) and the Goettingen miniature pig (GMP). The sulphur contents (% DW) were different in the three animal types (WB: 1.70-1.38 body, 0.54 ear; DP: 0.84-0.53 body, 0.50 ear; GMP: 2.28-2.51 body, 2.66 ear). The results of the histochemical analysis of SH- and -S-S- groups were clear, and densitometrical extinctions were highest in most body regions of the GMP for thiols and disulphides, followed by the DP for thiols, and the WB for disulphides. Absolute SC thickness was highest in the body of the GMP (62-80 mum), and generally lowest in the ear (20-38 mum) of all animal types. Relative SC thickness was the same for all animals in the body (40-66%), but lower in the ear (30%). Only -S-S- concentrations were correlated with SC thickness, and primarily in the GMP. Cytochemical analysis showed that high sulphur concentrations were obvious particularly in the CCE of corneal cells in the DP, as compared to the cytoplasm. Intracellular sulphur distribution was homogenous in the WB, and in the GMP, although in the latter at a higher concentration level. The results indicate breed-related effects on keratinisation in porcine corneal cells. Only the SC of the outer side of the ear of DP females is recommended as a model for humans.

Penetration of gold nanoparticles across the stratum corneum layer of thick-Skin.

PubMed

Raju, Gayathri; Katiyar, Neeraj; Vadukumpully, Sajini; Shankarappa, Sahadev A

2018-02-01

Transdermal particulate penetration across thick-skin, such as that of palms and sole, is particularly important for drug delivery for disorders such as small fiber neuropathies. Nanoparticle-based drug delivery across skin is believed to have much translational applications, but their penetration especially through thick-skin, is not clear. This study specifically investigates the effectiveness of gold nanoparticles (AuNPs) for thick-skin penetration, especially across the stratum corneum (SC) as a function of particle size. The thick-skinned hind-paw of rat was used to characterize depth and distribution of AuNPs of varying sizes, namely, 22±3, 105±11, and 186±20nm. Epidermal penetration of AuNPs was characterized both, in harvested skin from the hind-paw using a diffusion chamber, as well as in vivo. Harvested skin segments exposed to 22nm AuNPs for only 3h demonstrated higher penetration (p<0.05) as compared to the 105 and 186nm particles. In animal studies, hind-paw skin of adult rats exposed to AuNPs solution for the same time, demonstrated nanoparticles in blood on the 4th day, and histological analysis revealed AuNPs in epidermal layers just below the SC, with no apparent tissue response. We conclude that the thick-skin allows nanoparticle penetration and acts as a depot for release of AuNPs into circulation long after the initial exposure has ceased. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Differentiation of the epidermis in turtle: an immunocytochemical, autoradiographic and electrophoretic analysis.

PubMed

Alibardi, Lorenzo; Spisni, Enzo; Toni, Mattia

2004-01-01

Proteins involved in the process of cornification of turtle epidermis are not well known. The present immunocytochemical, electrophoretic and autoradiographic study reports on the localization patterns and molecular weights of keratins, which are cornification proteins, and of tritiated histidine in turtle epidermis. Alpha-keratins with a molecular weight of 40-62 kDa are present in the epidermis. Beta-keratin is mainly detectable in the stratum corneum of the carapace and plastron, but is rarely present or even absent in the corneous layer of limb, tail and neck epidermis. After electrophoresis and immunoblotting with an antibody against chicken scale beta-keratin, bands at 15-17, 22-24, and 36-38 kDa appeared. This antibody recognized weaker bands at 38-40 and 58-60 kDa in the soft epidermis. After reduction and carboxymethylation of proteins extracted from carapace and plastron, but not of proteins from the soft epidermis, protein bands at 15-17 and 35-37 kDa were found when using the anti-beta 1-keratin antibody. Loricrin-, filaggrin-, sciellin-, and transglutaminase-like immunostaining was detectable only in the transitional and lowermost corneous layers of the soft epidermis. Vesicular bodies in the transitional layer were immunolabeled by the anti-loricrin antibody, and weakly by the anti-filaggrin and anti-transglutaminase antibodies. In immunoblots, the anti-loricrin antibody reacted with a major band at 50-54 kDa in both carapace-plastron and soft epidermis. The anti-sciellin antibody detected major bands at 38-40 and 50 kDa in hard epidermis, and at 50 and 54-56 kDa in soft epidermis. Filaggrin-like immunostained bands were observed at 50-55 and 62-64 kDa. This immunostaining was probably due to a common epitope in filaggrin and some keratins. Histidine was evenly incorporated in the epidermis, and the ultrastructural study showed random labeling, often associated with keratin bundles of alpha and beta-keratinocytes. Histidine-labeled protein bands were

Immunohistochemical demonstration of keratins in the epidermal layers of the Malayan pangolin (Manis javanica), with remarks on the evolution of the integumental scale armour.

PubMed

Meyer, W; Liumsiricharoen, M; Suprasert, A; Fleischer, L G; Hewicker-Trautwein, M

2013-09-16

Using immunohistochemistry, the study demonstrates the distribution of keratins (pan-keratin with CK1-8, 10, 14-16, 19; keratins CK1, 5, 6, 9, 10; hair keratins AE13, AE14) in the epidermis of the Malayan pangolin (Manis javanica). A varying reaction spectrum was observed for pan-keratin, with body region-dependent negative to very strong reaction intensities. The dorsolateral epidermis exhibited positive reactions only in its vital layers, whereas the abdominal epidermis showed strong positive reactions in the soft two outer strata. The single acidic and basic-to-neutral (cyto)keratins produced clear variations compared to the pan-keratin tinging. E.g., CK1 appeared in all epidermal layers of both body regions, except for the ventral stratum corneum, whereas CK5, 6, 9, 10 were restricted to the soft ventral epidermis. Here, distinctly positive reactions were confined to the stratum granulosum, except for CK6 that appeared in the soft stratum corneum. A different staining pattern was obvious for the hair keratins, i.e., positive reactions of AE13 concentrated only in the granular layer of the dorsal epidermis. In the abdominal epidermis, remarkable tinging for AE14 was visible in the stratum basale, decreasing toward the corneal layer, but was also found in the outer root sheath cells of the hair follicles in the ventral body part. Our findings are discussed related to the evolution of the horny dorsal scales of the pangolin, which may have started from the tail root, projecting forward to the head.

Relative uptake of minoxidil into appendages and stratum corneum and permeation through human skin in vitro.

PubMed

Grice, Jeffrey E; Ciotti, Susan; Weiner, Norman; Lockwood, Peter; Cross, Sheree E; Roberts, Michael S

2010-02-01

We examined uptake of the model therapeutic agent, minoxidil, into appendages, stratum corneum (SC), and through human skin, under the influence of different vehicles. Quantitative estimation of therapeutic drug deposition into all three areas has not previously been reported. Finite doses of minoxidil (2%, w/v) in formulations containing varying amounts of ethanol, propylene glycol (PG), and water (60:20:20, 80:20:0, and 0:80:20 by volume, respectively) were used. Minoxidil in SC (by tape stripping), appendages (by cyanoacrylate casting), and receptor fluid was determined by liquid scintillation counting. At early times (30 min, 2 h), ethanol-containing formulations (60:20:20 and 80:20:0) caused significantly greater minoxidil retention in SC and appendages, compared to the formulation lacking ethanol (0:80:20). A significant increase in minoxidil receptor penetration occurred with the PG-rich 0:80:20 formulation after 12 h. We showed that deposition of minoxidil into appendages, SC, and skin penetration into receptor fluid were similar in magnitude. Transport by the appendageal route is likely to be a key determinant of hair growth promotion by minoxidil. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association.

Ethnic differences in stratum corneum functions between Chinese and Thai infants residing in Bangkok, Thailand.

PubMed

Fujimura, Tsutomu; Miyauchi, Yuki; Shima, Kyoko; Hotta, Mitsuyuki; Tsujimura, Hisashi; Kitahara, Takashi; Takema, Yoshinori; Palungwachira, Pakhawadee; Laohathai, Diane; Chanthothai, Jetchawa; Nararatwanchai, Thamthiwat

2018-01-01

Ethnic and racial differences in infant skin have not been well characterized. The purpose of this study was to establish whether there are ethnic differences and similarities in the stratum corneum (SC) functions of Thai and Chinese infants. Healthy infants 6 to 24 months of age (N = 60; 30 Thai, 30 Chinese) who resided in Bangkok, Thailand, were enrolled. Transepidermal water loss (TEWL) and SC hydration (capacitance) on the thigh, buttock, and upper arm were measured. Ceramide content was determined in the SC on the upper arm. SC hydration was not remarkably different between the two ethnicities at any site measured, but TEWL was significantly higher in Chinese infants than in Thai infants at all sites. Hydration of the SC was not significantly correlated with age in either ethnicity. TEWL had significant but weak correlations with age on the thigh and upper arm in Thai infants. Ceramide content was significantly higher in Chinese SC than in Thai SC. No relationship between ceramide content and TEWL or hydration was observed in either ethnicity. The significant differences in TEWL and ceramide contents between Chinese and Thai infant skin could prove useful in designing skin care and diapering products that are best suited for each ethnicity. © 2017 Wiley Periodicals, Inc.

Ex vivo skin absorption of terpenes from Vicks VapoRub ointment.

PubMed

Cal, Krzysztof; Sopala, Monika

2008-08-01

The pharmaceutical market offers a wide range of inhalant drug products applied on the skin that contain essential oils and/or their isolated compounds, i.e. terpenes. Because there are few data concerning the skin penetration of terpenes, especially from complex carriers, the goal of this study was to determine the ex vivo skin absorption kinetics of chosen terpenes, namely eucalyptol, menthol, camphor, alpha-pinene, and beta-pinene, from the product Vicks VapoRub. Human cadaver skin was placed in a flow-through diffusion chamber and the product was applied for 15, 30, and 60 min. After the application time the skin was separated into layers using a tape-stripping technique: three fractions of stratum corneum and epidermis with dermis, and terpenes amounts in the samples were determined by gas-chromatography. The investigated terpenes showed different absorption characteristics related to their physicochemical properties and did not permeate through the skin into the acceptor fluid. Eucalyptol had the largest total accumulation in the stratum corneum and in the epidermis with dermis, while alpha-pinene penetrated into the skin in the smallest amount. The short time in which saturation of the stratum corneum with the terpenes occurred and the high accumulation of most of the investigated terpenes in the skin layers proved that these compounds easily penetrate and permeate the stratum corneum and that in vivo they may easily penetrate into the blood circulation.

Plantar skin in type II diabetes: an investigation of protein glycation and biomechanical properties of plantar epidermis.

PubMed

Hashmi, Farina; Malone-Lee, James; Hounsell, Elizabeth

2006-01-01

The generation of thickened plantar stratum corneum (SC) in response to elevated pressures, places individuals with diabetes at risk of ulceration. Such a response may culminate from altered biochemical and physical states of the epidermis as a result of non-enzymatic glycation (NEG). The objective of this study was to quantify specific glycation products generated in plantar epidermal proteins in individuals with Type 2 Diabetes Mellitus (T2DM) and age-matched controls (n = 103 and n = 87, respectively) and to compare these data with the viscoelastic properties (in vivo) of the epidermis. Plantar SC and venous blood samples were collected from all participants for the quantification of furosine and pentosidine using high performance liquid chromatography (HPLC). The viscoelastic properties of plantar epidermis were measured by the application of negative pressure on the surface of the skin. Plantar epidermal thickness was measured using high frequency (20 MHz) ultrasonography. There was a significantly greater concentration of pentosidine in the SC samples from people with T2DM (p = 0.001). There was no correlation between the concentration of glycated proteins in the epidermal proteins and serum proteins (furosine r = - 0.115, pentosidine r = - 0.023). The plasticity of the epidermis was significantly lower in the T2DM group than the control group (p = 0.007). The results suggest that alterations in the glycation of plantar epidermal proteins may constitute additional aggravators of ulceration in people with T2DM.

In vivo skin moisturizing measurement by high-resolution 3 Tesla magnetic resonance imaging.

PubMed

Mesrar, J; Ognard, J; Garetier, M; Chechin, D; Misery, L; Ben Salem, D

2017-08-01

Magnetic resonance imaging (MRI) is rarely used for the exploration of skin, even if studies have validated both feasibility of skin MRI and its interest for anatomical, physiological, and biochemical study of the skin. The purpose of this study is to explore moisturizing of the different skin layers using 3-T scan. An MRI of the heel's skin was performed using a 23 mm coil diameter on a 3T scan with a FFE (Fast Field Echo) 3D T1-weighted sequence and a TSE (Turbo Spin Echo) calculation T2-weighted sequence (pixels size of respectively 60 and 70 μm). This study was conducted on 35 healthy volunteers, who were scanned before applying moisturizer topic and 1 h after applying it. Region of interest in the stratum corneum, the epidermis and the dermis were generated on the T2 mapping. The thickness of each layer was measured. The T1 sequence allowed accurate cross-examination repositioning to ensure the comparability of the measurements. Among the 35 cases, two were excluded from the analysis because of movement artifacts. Measurements before and after moisturizer topic application displayed a T2 increase of 48.94% (P < 0.0001) in the stratum corneum and of 5.45% (P < 0.0001) in the epidermis yet without significant difference in the dermis. There was no significant link between the thickness of the stratum corneum and the T2 increase. However, there was a strong correlation between the thickness of the stratum corneum and the thickness of the epidermis (P < 0.001; rhô=0.72). High-resolution MRI allows fine exploration of anatomical and physiological properties of the skin and can further be used to extend the studies of skin hydration. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Variations in the ceramide profile in different seasons and regions of the body contribute to stratum corneum functions.

PubMed

Ishikawa, Junko; Shimotoyodome, Yoshie; Ito, Shotaro; Miyauchi, Yuki; Fujimura, Tsutomu; Kitahara, Takashi; Hase, Tadashi

2013-03-01

The objective of this study was to clarify variations of the ceramide (CER) profile in human stratum corneum (SC) in different seasons and in different regions of the body and to estimate the contributions of CERs to the SC barrier and water-holding functions. Based on the information that there are great variations of SC functions among body sites, we compared the CER profiles obtained from ten different anatomical sites in healthy Japanese males in four seasons. Not only the physiological parameters of skin but also the CER profile showed body region and seasonal variations. The total CER level, the CER composition and the C34-CER[NS] species displayed strong correlations with the values of transepidermal water loss and capacitance throughout the body. Especially in the cheek, a strong correlation between the capacitance and the CER profile was observed. There were seasonal variations of the CER profile in the lip, upper arm and palm. Our results indicate that regional and seasonal variations of the CER profile may contribute to SC functions.

Scalp stratum corneum histamine levels: novel sampling method reveals association with itch resolution in dandruff/seborrhoeic dermatitis treatment.

PubMed

Kerr, Kathy; Schwartz, James R; Filloon, Thomas; Fieno, Angela; Wehmeyer, Ken; Szepietowski, Jacek C; Mills, Kevin J

2011-06-01

Dandruff and seborrhoeic dermatitis are accompanied by bothersome itch. We have established a novel non-invasive methodology to sample histamine levels in the stratum corneum in order to facilitate an understanding of pruritogenesis in this condition. Histamine levels were assessed in two groups of subjects with dandruff before and after 3 weeks of treatment with a commercial potentiated zinc pyrithione shampoo. A comparative population without dandruff was also studied. Itch self-perception was quantified on a visual analogue scale. The histamine level in subjects with dandruff was more than twice that in those who did not have dandruff. Under conditions known to resolve flaking symptoms, the shampoo led to a reduction in histamine in subjects with dandruff to a level that was statistically indistinguishable from those who did not have dandruff. This reduction in histamine was accompanied by a highly significant reduction in the perception of itch intensity. These findings suggest an association between the subjective perception of itch in the scalp and the level of histamine in the skin.

Comparison of protocols measuring diffusion and partition coefficients in the stratum corneum

PubMed Central

Rothe, H.; Obringer, C.; Manwaring, J.; Avci, C.; Wargniez, W.; Eilstein, J.; Hewitt, N.; Cubberley, R.; Duplan, H.; Lange, D.; Jacques‐Jamin, C.; Klaric, M.; Schepky, A.

2017-01-01

Abstract Partition (K) and diffusion (D) coefficients are important to measure for the modelling of skin penetration of chemicals through the stratum corneum (SC). We compared the feasibility of three protocols for the testing of 50 chemicals in our main studies, using three cosmetics‐relevant model chemicals with a wide range of logP values. Protocol 1: SC concentration‐depth profile using tape‐stripping (measures KSC/v and DSC/HSC 2, where HSC is the SC thickness); Protocol 2A: incubation of isolated SC with chemical (direct measurement of KSC/v only) and Protocol 2B: diffusion through isolated SC mounted on a Franz cell (measures KSC/v and DSC/HSC 2, and is based on Fick's laws). KSC/v values for caffeine and resorcinol using Protocol 1 and 2B were within 30% of each other, values using Protocol 2A were ~two‐fold higher, and all values were within 10‐fold of each other. Only indirect determination of KSC/v by Protocol 2B was different from the direct measurement of KSC/v by Protocol 2A and Protocol 1 for 7‐EC. The variability of KSC/v for all three chemicals using Protocol 2B was higher compared to Protocol 1 and 2A. DSC/HSC 2 values for the three chemicals were of the same order of magnitude using all three protocols. Additionally, using Protocol 1, there was very little difference between parameters measured in pig and human SC. In conclusion, KSC/v, and DSC values were comparable using different methods. Pig skin might be a good surrogate for human skin for the three chemicals tested. Copyright © 2017 The Authors Journal of Applied Toxicology published by John Wiley & Sons Ltd. PMID:28139006

Organization of lipids in avian stratum corneum: Changes with temperature and hydration.

PubMed

Champagne, Alex M; Allen, Heather C; Bautista-Jimenez, Robin C; Williams, Joseph B

2016-02-01

In response to increases in ambient temperature (Ta), many animals increase total evaporative water loss (TEWL) through their skin and respiratory passages to maintain a constant body temperature, a response that compromises water balance. In birds, cutaneous water loss (CWL) accounts for approximately 65% of TEWL at thermoneutral temperatures. Although the proportion of TEWL accounted for by CWL decreases to only 25% at high Ta, the magnitude of CWL still increases, suggesting changes in the barrier function of the skin. The stratum corneum (SC) is composed of flat, dead cells called corneocytes embedded in a matrix of lipids, many of which arrange in layers called lamellae. The classes of lipids that comprise these lamellae, and their attendant physical properties, determine the rate of CWL. We measured CWL at 25, 30, 35, and 40 °C in House Sparrows (Passer domesticus) caught in the winter and summer, and in sparrows acclimated to warm and cold lab environments. We then used Fourier transform infrared spectroscopy to measure lipid-lipid and lipid-water interactions in the SC under different conditions of temperature and hydration, and correlated these results with lipid classes in the SC. As CWL increased at higher temperatures, the amount of gauche defects in lipid alkyl chains increased, indicating that lipid disorder is partially responsible for higher CWL at high temperatures. However, variation in CWL between groups could not be explained by the amount of gauche defects, and this remaining variation may be attributed to greater amounts of cerebrosides in birds with low CWL, as the sugar moieties of cerebrosides lie outside lipid lamellae and form strong hydrogen bonds with water molecules. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The use of D-optimal mixture design in optimising okara soap formulation for stratum corneum application.

PubMed

Borhan, Farrah Payyadhah; Abd Gani, Siti Salwa; Shamsuddin, Rosnah

2014-01-01

Okara, soybean waste from tofu and soymilk production, was utilised as a natural antioxidant in soap formulation for stratum corneum application. D-optimal mixture design was employed to investigate the influence of the main compositions of okara soap containing different fatty acid and oils (virgin coconut oil A (24-28% w/w), olive oil B (15-20% w/w), palm oil C (6-10% w/w), castor oil D (15-20% w/w), cocoa butter E (6-10% w/w), and okara F (2-7% w/w)) by saponification process on the response hardness of the soap. The experimental data were utilized to carry out analysis of variance (ANOVA) and to develop a polynomial regression model for okara soap hardness in terms of the six design factors considered in this study. Results revealed that the best mixture was the formulation that included 26.537% A, 19.999% B, 9.998% C, 16.241% D, 7.633% E, and 7.000% F. The results proved that the difference in the level of fatty acid and oils in the formulation significantly affects the hardness of soap. Depending on the desirable level of those six variables, creation of okara based soap with desirable properties better than those of commercial ones is possible.

The effects of esterified solvents on the diffusion of a model compound across human skin: an ATR-FTIR spectroscopic study.

PubMed

McAuley, W J; Chavda-Sitaram, S; Mader, K T; Tetteh, J; Lane, M E; Hadgraft, J

2013-04-15

Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy has been used to investigate the effects of three fatty acid esters on skin permeation. Propylene glycol diperlargonate (DPPG), isopropyl myristate (IPM) and isostearyl isostearate (ISIS) were selected as pharmaceutically relevant solvents with a range of lipophilicities and cyanophenol (CNP) was used as a model drug. The resultant data were compared with that obtained when water was used as the solvent. The diffusion of CNP, DPPG and IPM across epidermis was successfully described by a Fickian model. When ISIS was used as a solvent Fickian behaviour was only obtained across isolated stratum corneum suggesting that the hydrophilic layers of the epidermis interfere with the permeation of the hydrophobic ISIS. The diffusion coefficients of CNP across epidermis in the different solvents were not significantly different. Using chemometric data analysis diffusion profiles for the solvents were deconvoluted from that of the skin and modelled. Each of these solvents was found to diffuse at a faster rate across the skin than CNP. DPPG considerably increased the concentration of CNP in the stratum corneum in comparison with the other solvents indicating strong penetration enhancer potential. In contrast IPM produced a similar CNP concentration in the stratum corneum to water with ISIS resulting in a lower CNP concentration suggesting negligible enhancement and penetration retardation effects for these two solvents respectively. Copyright © 2013 Elsevier B.V. All rights reserved.

Regenerated keratin membrane to match the in vitro drug diffusion through human epidermis

PubMed Central

Selmin, Francesca; Cilurzo, Francesco; Aluigi, Annalisa; Franzè, Silvia; Minghetti, Paola

2012-01-01

This work aimed to develop membranes made of regenerated keratin and ceramides (CERs) to match the barrier property of the human stratum corneum in in vitro percutaneous absorption studies. The membrane composition was optimized on the basis of the in vitro drug diffusion profiles of ibuprofen, propranolol and testosterone chosen as model drugs on the basis of their different diffusion and solubility properties. The data were compared to those obtained using human epidermis. The ATR-FTIR and SEM analyses revealed that CERs were suspended into the regenerated keratin matrix, even if a partial solubilization occurred. It resulted in the membranes being physically stable after exposure to aqueous buffer and/or mineral oil and the fluxes of ibuprofen and propranolol from these vehicles through membranes and human skin were of the same order of magnitude. The best relationship with human epidermis data was obtained with 180 μm-thick membrane containing 1% ceramide III and 1% ceramide VI. The data on the testosterone diffusion were affected by the exposure of the membrane to a water/ethanol solution over a prolonged period of time, indicating that such an organic solvent was able to modify the supermolecular organization of keratin and CERs. The keratin/CER membranes can represent a simplified model to assay the in vitro skin permeability study of small molecules. PMID:25755997

Size-dependent penetration of nanoemulsions into epidermis and hair follicles: implications for transdermal delivery and immunization

PubMed Central

Su, Rui; Fan, Wufa; Yu, Qin; Dong, Xiaochun; Qi, Jianping; Zhu, Quangang; Zhao, Weili; Wu, Wei; Chen, Zhongjian; Li, Ye; Lu, Yi

2017-01-01

Nanoemulsions have been widely applied to dermal and transdermal drug delivery. However, whether and to what depth the integral nanoemulsions can permeate into the skin is not fully understood. In this study, an environment-responsive dye, P4, was loaded into nanoemulsions to track the transdermal translocation of the nanocarriers, while coumarin-6 was embedded to represent the cargoes. Particle size has great effects on the transdermal transportation of nanoemulsions. Integral nanoemulsions with particle size of 80 nm can diffuse into but not penetrate the viable epidermis. Instead, these nanoemulsions can efficiently fill the whole hair follicle canals and reach as deep as 588 μm underneath the dermal surfaces. The cargos are released from the nanoemulsions and diffuse into the surrounding dermal tissues. On the contrary, big nanoemulsions, with mean particle size of 500 nm, cannot penetrate the stratum corneum and can only migrate along the hair follicle canals. Nanoemulsions with median size, e.g. 200 nm, show moderate transdermal permeation effects among the three-size nanoemulsions. In addition, colocalization between nanoemulsions and immunofluorescence labeled antigen-presenting cells was observed in the epidermis and the hair follicles, implying possible capture of nanoemulsions by these cells. In conclusion, nanoemulsions are advantageous for transdermal delivery and potential in transcutaneous immunization. PMID:28465469

A Coarse-grained Model of Stratum Corneum Lipids: Free Fatty Acids and Ceramide NS

PubMed Central

Moore, Timothy C.; Iacovella, Christopher R.; Hartkamp, Remco; Bunge, Annette L.; McCabe, Clare

2017-01-01

Ceramide (CER)-based biological membranes are used both experimentally and in simulations as simplified model systems of the skin barrier. Molecular dynamics studies have generally focused on simulating preassembled structures using atomistically detailed models of CERs, which limit the system sizes and timescales that can practically be probed, rendering them ineffective for studying particular phenomena, including self-assembly into bilayer and lamellar superstructures. Here, we report on the development of a coarse-grained (CG) model for CER NS, the most abundant CER in human stratum corneum. Multistate iterative Boltzmann inversion is used to derive the intermolecular pair potentials, resulting in a force field that is applicable over a range of state points and suitable for studying ceramide self-assembly. The chosen CG mapping, which includes explicit interaction sites for hydroxyl groups, captures the directional nature of hydrogen bonding and allows for accurate predictions of several key structural properties of CER NS bilayers. Simulated wetting experiments allow the hydrophobicity of CG beads to be accurately tuned to match atomistic wetting behavior, which affects the whole system since inaccurate hydrophobic character is found to unphysically alter the lipid packing in hydrated lamellar states. We find that CER NS can self-assemble into multilamellar structures, enabling the study of lipid systems more representative of the multilamellar lipid structures present in the skin barrier. The coarse-grained force field derived herein represents an important step in using molecular dynamics to study the human skin barrier, which gives a resolution not available through experiment alone. PMID:27564869

Distribution of caspase-14 in epidermis and hair follicles is evolutionarily conserved among mammals.

PubMed

Alibardi, Lorenzo; Tschachler, Erwin; Eckhart, Leopold

2005-10-01

Caspase-14, a member of the caspase family of cysteine proteases, is almost exclusively expressed in the epidermis. Studies on human and mouse cells and tissues have implicated caspase-14 in terminal differentiation of epidermal keratinocytes and in the formation of the stratum corneum. Here we investigated evolutionary aspects of the role of caspase-14 by analyzing its distribution in the epidermis and hair follicles of representative species of placental mammals, marsupials, and monotremes. Immunocytochemical staining showed that caspase-14 is consistently expressed in the granular and corneous layer of the epidermis of all mammalian species investigated. Ultrastructural analysis using gold-labeled anticaspase-14 antibodies revealed that caspase-14 is associated preferentially with keratin bundles and amorphous material of keratohyalin granules, but is also present in nuclei of transitional cells of the granular layer and in corneocytes. In hair follicles, caspase-14 was diffusely present in cornifying cells of the outer root sheath, in the companion layer, and, most abundantly, in the inner root sheath of all mammalian species here analyzed. In Henle and Huxley layers of the inner root sheath, labeling was seen in nuclei and, more diffusely, among trichohyalin granules of cornifying cells. In summary, the tissue expression pattern and the intracellular localization of caspase-14 are highly conserved among diverse mammalian species, suggesting that this enzyme is involved in a molecular process that appeared early in the evolution of mammalian skin. The association of caspase-14 with keratohyalin and trichohyalin granules may indicate a specific role of caspase-14 in the maturation of these keratinocyte-specific structures.

The Use of D-Optimal Mixture Design in Optimising Okara Soap Formulation for Stratum Corneum Application

PubMed Central

Borhan, Farrah Payyadhah; Abd Gani, Siti Salwa; Shamsuddin, Rosnah

2014-01-01

Okara, soybean waste from tofu and soymilk production, was utilised as a natural antioxidant in soap formulation for stratum corneum application. D-optimal mixture design was employed to investigate the influence of the main compositions of okara soap containing different fatty acid and oils (virgin coconut oil A (24–28% w/w), olive oil B (15–20% w/w), palm oil C (6–10% w/w), castor oil D (15–20% w/w), cocoa butter E (6–10% w/w), and okara F (2–7% w/w)) by saponification process on the response hardness of the soap. The experimental data were utilized to carry out analysis of variance (ANOVA) and to develop a polynomial regression model for okara soap hardness in terms of the six design factors considered in this study. Results revealed that the best mixture was the formulation that included 26.537% A, 19.999% B, 9.998% C, 16.241% D, 7.633% E, and 7.000% F. The results proved that the difference in the level of fatty acid and oils in the formulation significantly affects the hardness of soap. Depending on the desirable level of those six variables, creation of okara based soap with desirable properties better than those of commercial ones is possible. PMID:25548777

Further investigations on the role of ascorbic acid in stratum corneum lipid models after UV exposure.

PubMed

Trommer, Hagen; Böttcher, Rolf; Huschka, Christoph; Wohlrab, Wolfgang; Neubert, Reinhard H H

2005-08-01

This study is the continuation of our research into vitamin C and its possible effects on human skin after topical administration. The effects of ascorbic acid, iron ions and UV irradiation on stratum corneum lipid models were investigated. The lipid models used were: a simple system (linolenic acid dispersion), a complex system (liposomes consisting of dipalmitoylphosphatidylcholine, cholesterol and linolenic acid) and complex systems with additionally incorporated ceramides (types III and IV). The lipid peroxidation was quantified by the thiobarbituric acid assay. A human adult low-calcium high-temperature (HaCaT) keratinocytes cell culture was used as a second in-vitro model. The amount of intracellular peroxides was determined by measuring the fluorescence intensity using the dihydrorhodamine 123 assay. Electron paramagnetic resonance spectroscopy was used to study the influence of ascorbic acid and iron ions on the signal intensity of 5-doxylstearic acid during UV exposure. Ascorbic acid showed prooxidative properties in the thiobarbituric acid assay whereas cell protection was measured in the HaCaT keratinocytes experiments. Electron paramagnetic resonance investigations revealed different extents of free radical production generated by iron ions, ascorbic acid and UV irradiation. In evaluating the results from this study new aspects of the mechanism of lipid damage caused by these three factors were suggested, transcending the simple redox behaviour of ascorbic acid.

Non steady-state descriptions of drug permeation through stratum corneum. I. The biphasic brick-and-mortar model.

PubMed

Heisig, M; Lieckfeldt, R; Wittum, G; Mazurkevich, G; Lee, G

1996-03-01

The diffusion equation should be solved for the non-steady-state problem of drug diffusion within a two-dimensional, biphasic stratum corneum membrane having homogeneous lipid and corneocyte phases. A numerical method was developed for a brick-and-mortar SC-geometry, enabling an explicit solution for time-dependent drug concentration within both phases. The lag time and permeability were calculated. It is shown how the barrier property of this model membrane depends on relative phase permeability, corneocyte alignment, and corneocyte-lipid partition coefficient. Additionally, the time-dependent drug concentration profiles within the membrane can be observed during the lag and steady-state phases. The model SC-membrane predicts, from purely morphological principles, lag times and permeabilities that are in good agreement with experimental values. The long lag times and very small permeabilities reported for human SC can only be predicted for a highly-staggered corneocyte geometry and corneocytes that are 1000 times less permeable than the lipid phase. Although the former conclusion is reasonable, the latter is questionable. The elongated, flattened corneocyte shape renders lag time and permeability insensitive to large changes in their alignment within the SC. Corneocyte/lipid partitioning is found to be fundamentally different to SC/donor partitioning, since increasing drug lipophilicity always reduces both lag time and permeability.

Sun-induced changes of stratum corneum hydration vary with age and gender in a normal Chinese population.

PubMed

Liu, Zhili; Song, Shunpeng; Luo, Wenhai; Elias, Peter M; Man, Mao-Qiang

2012-02-01

Previous studies have demonstrated that sun-induced alteration of epidermal permeability barrier function varies with gender and age. In the present study, we assess the stratum corneum (SC) hydration in sun-exposed males and females. A total of 168 subjects (84 males and 84 females) aged 19-75 years were enrolled. A multifunctional skin physiology monitor was used to measure SC hydration. In comparison with non-sun exposure, sun exposure does not cause a significant change in SC hydration in either young males or young females, whereas in aged females, a significant reduction of SC hydration is seen on the forehead and the dorsal hand of sun-exposed subjects. SC hydration on the canthus of both aged males and aged females is significantly lower than that of young subjects. Additionally, SC hydration on the dorsal hand of aged females is also significantly lower as compared with young females. Sun-induced reduction of SC hydration is more evident on the dorsal hand of aged females than that of males (P<0.001). Moreover, the SC rehydration capacity is significantly lower in sun-exposed aged females than in age-matched males. These results demonstrated that sun-induced changes of the SC hydration property vary with age and gender. © 2011 John Wiley & Sons A/S.

Confocal Raman microspectroscopy of stratum corneum: a pre-clinical validation study.

PubMed

Wu, J; Polefka, T G

2008-02-01

Skin moisturization is not only important for maintaining skin functional properties but also has great impact on the skin's aesthetic properties. The top layer of the skin, the stratum corneum (SC), plays a key role in protecting and preventing against external aggressions as well as in regulating water flux in and out. Confocal Raman microspectroscopy is the first commercially available technique that provides a non-invasive, in vivo method to determine depth profiles of water concentration in the skin, however, in this case it was applied in an in vitro setting. As the first phase of validating the usefulness of confocal Raman microspectroscopy, we used porcine skin as a surrogate for human skin. Water concentration profiles were obtained using confocal Raman microspectroscopy from isolated pigskin SC and compared with that using the Karl Fischer titration method. The two methods correlated very well with a regression coefficient of 1.07 as well as a correlation coefficient, R(2) = 0.989, which demonstrated the consistency and accuracy of confocal Raman microspectroscopy for water concentration determination. To evaluate the instrument's response to different skin care/cleansing products, a wide range of products were tested to compare their skin moisturization ability. Among those tested were a lotion, commercial soap bar, syndet bar, traditional non-emollient shower gel (water, Sodium Laureth Ether Sulfate (SLES), cocamidopropyl betaine system) and emollient containing shower gel (water, sunflower oil, SLES, cocamidopropyl betaine, glycerin, petrolatum). The results were consistent with what was expected. The water content on skin treated with (A) lotion was significantly higher than the non-treated control; (B) syndet bar-treated skin had a significantly higher water content than soap-based bar-treated sites; (C) non-emollient shower gel washed sites were more moisturized than soap-based bar-treated samples; and (D) emollient shower gel-treated skin was

Comparison of protocols measuring diffusion and partition coefficients in the stratum corneum.

PubMed

Rothe, H; Obringer, C; Manwaring, J; Avci, C; Wargniez, W; Eilstein, J; Hewitt, N; Cubberley, R; Duplan, H; Lange, D; Jacques-Jamin, C; Klaric, M; Schepky, A; Grégoire, S

2017-07-01

Partition (K) and diffusion (D) coefficients are important to measure for the modelling of skin penetration of chemicals through the stratum corneum (SC). We compared the feasibility of three protocols for the testing of 50 chemicals in our main studies, using three cosmetics-relevant model chemicals with a wide range of logP values. Protocol 1: SC concentration-depth profile using tape-stripping (measures K SC/v and D SC /H SC 2 , where H SC is the SC thickness); Protocol 2A: incubation of isolated SC with chemical (direct measurement of K SC/v only) and Protocol 2B: diffusion through isolated SC mounted on a Franz cell (measures K SC/v and D SC /H SC 2 , and is based on Fick's laws). K SC/v values for caffeine and resorcinol using Protocol 1 and 2B were within 30% of each other, values using Protocol 2A were ~two-fold higher, and all values were within 10-fold of each other. Only indirect determination of K SC/v by Protocol 2B was different from the direct measurement of K SC/v by Protocol 2A and Protocol 1 for 7-EC. The variability of K SC/v for all three chemicals using Protocol 2B was higher compared to Protocol 1 and 2A. D SC /H SC 2 values for the three chemicals were of the same order of magnitude using all three protocols. Additionally, using Protocol 1, there was very little difference between parameters measured in pig and human SC. In conclusion, K SC/v, and D SC values were comparable using different methods. Pig skin might be a good surrogate for human skin for the three chemicals tested. Copyright © 2017 The Authors Journal of Applied Toxicology published by John Wiley & Sons Ltd. Copyright © 2017 The Authors Journal of Applied Toxicology published by John Wiley & Sons Ltd.

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

PubMed

Hoath, Steven B; Leahy, D G

2003-12-01

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.

Choline acetyltransferase-like immunofluorescence in epidermis of human skin.

PubMed

Johansson, O; Wang, L

1993-01-01

Using the indirect immunofluorescence approach the occurrence of choline acetyltransferase-like immunoreactivity in epidermis, except stratum basale, of human skin is described. Immunoreactive cells were also found in hair follicles, sweat gland ducts and sebaceous glands.

Presence and persistence of a highly ordered lipid phase state in the avian stratum corneum.

PubMed

Champagne, Alex M; Pigg, Victoria A; Allen, Heather C; Williams, Joseph B

2018-06-07

To survive high temperatures in a terrestrial environment, animals must effectively balance evaporative heat loss and water conservation. In passerine birds, cutaneous water loss (CWL) is the primary avenue of water loss at thermoneutral temperatures and increases slightly as ambient temperature increases, indicating a change in the permeability of the skin. In the stratum corneum (SC), the outermost layer of the skin, lipids arranged in layers called lamellae serve as the primary barrier to CWL in birds. The permeability of these lamellae depends in large part on the ability of lipid molecules to pack closely together in an ordered orthorhombic phase state. However, as temperature increases, lipids of the SC become more disordered, and may pack in more permeable hexagonal or liquid crystalline phase states. In this study, we used Fourier transform infrared spectroscopy to monitor the phase state of lipids in the SC of house sparrows ( Passer domesticus ) at skin temperatures ranging from 25 to 50°C. As temperature increased, lipids became slightly more disordered, but remained predominantly in the orthorhombic phase, consistent with the small increase in CWL observed in house sparrows as ambient temperature increases. These results differ considerably from studies on mammalian SC, which find a predominantly hexagonal arrangement of lipids at temperatures above 37°C, and the increased order in avian SC may be explained by longer lipid chain length, scarcity of cholesterol and the presence of cerebrosides. Our results lend further insight into the arrangement and packing of individual lipid molecules in avian SC. © 2018. Published by The Company of Biologists Ltd.

The Effect of Gromwell (Lithospermum erythrorhizon) Extract on the Stratum Corneum Hydration and Ceramides Content in Atopic Dermatitis Patients.

PubMed

Cho, Hee Ryung; Cho, Yunhi; Kim, Juyoung; Seo, Dae Bang; Kim, Sung Han; Lee, Sang Jun; Kim, Nack In

2008-06-01

A disruption of the balance between the water content of the stratum corneum (SC) and skin surface lipids may lead to the clinical manifestation of dryness of skin in patients with atopic dermatitis (AD). To determine whether supplementation of gromwell (Lithospermum erythrorhizon), one of herbs used in East Asia in remedies for various abnormal skin conditions, may improve the SC level of hydration and ceramides, major lipid in SC in patients with AD. A total of 28 subjects with AD were randomly assigned into two groups: either gromwell group received dextrose contained capsules with 1.5 g of gromwell extracts or placebo group received only dextrose contained capsules for 10 weeks. In contrast to no alteration of SC hydration and ceramides in placebo group, the SC hydration in gromwell group was significantly increased in parallel with an increase of SC ceramides. Furthermore, % increase of SC hydration in gromwell group bore a positive correlation with the clinical severity, which suggests that the increase of SC hydration in gromwell group was more effective as AD was more severe. Supplementation of gromwell improves SC hydration in parallel with an increase of ceramides in part.

The Effect of Gromwell (Lithospermum erythrorhizon) Extract on the Stratum Corneum Hydration and Ceramides Content in Atopic Dermatitis Patients

PubMed Central

Cho, Hee Ryung; Cho, Yunhi; Kim, Juyoung; Seo, Dae Bang; Kim, Sung Han; Lee, Sang Jun

2008-01-01

Background A disruption of the balance between the water content of the stratum corneum (SC) and skin surface lipids may lead to the clinical manifestation of dryness of skin in patients with atopic dermatitis (AD). Objective To determine whether supplementation of gromwell (Lithospermum erythrorhizon), one of herbs used in East Asia in remedies for various abnormal skin conditions, may improve the SC level of hydration and ceramides, major lipid in SC in patients with AD. Methods A total of 28 subjects with AD were randomly assigned into two groups: either gromwell group received dextrose contained capsules with 1.5 g of gromwell extracts or placebo group received only dextrose contained capsules for 10 weeks. Results In contrast to no alteration of SC hydration and ceramides in placebo group, the SC hydration in gromwell group was significantly increased in parallel with an increase of SC ceramides. Furthermore, % increase of SC hydration in gromwell group bore a positive correlation with the clinical severity, which suggests that the increase of SC hydration in gromwell group was more effective as AD was more severe. Conclusion Supplementation of gromwell improves SC hydration in parallel with an increase of ceramides in part. PMID:27303161

Investigation of depilatory mechanism by use of multiphoton fluorescent microscopy

NASA Astrophysics Data System (ADS)

Lin, Chiao-Ying; Lee, Gie-ne; Jee, Shiou-Hwa; Dong, Chen-Yuan; Lin, Sung-Jan

2007-07-01

Transdermal drug delivery provides a non-invasive route of drug administration, and can be a alternative method to oral delivery and injection. The stratum corneum (SC) of skin acts as the main barrier to transdermal drug delivery. Studies suggest that depilatory enhances permeability of drug through the epidermis. However, transdermal delivery pathway and mechanism are not completely understood. Previous studies have found that depilatory changes the keratinocytes of epidermis, and cause the protein in combination with lipid extraction of SC to become disordered. Nevertheless, those studies did not provide images of those processes. The aim of this study is to characterize the penetration enhancing effect of depilatory agent and the associated structural alterations of stratum corneum. Fresh human foreskin is treated by a depilatory agent for 10 minutes and then subjected to the treatment of fluorescent model drugs of hydrophilic rhodamine and hydrophobic rhodamine-RE. The penetration of model drugs is imaged and quantified by multiphoton microscopy. Our results showed that the penetration of both hydrophilic and hydrophobic agents can be enhanced and multifocal detachment of surface corneocytes is revealed. Nile red staining revealed, instead of a regular motar distribution of lipid around the brick of corneocytes, a disorganized and homogenized pattern of lipid distribution. We concluded that depilatory agents enhance drug penetration by disrupting both the cellular integrity of corneocytes and the regular packing of intercellular lipid of stratum corneum.

Tracking solvents in the skin through atomically resolved measurements of molecular mobility in intact stratum corneum

PubMed Central

Topgaard, Daniel; Sparr, Emma

2017-01-01

Solvents are commonly used in pharmaceutical and cosmetic formulations and sanitary products and cleansers. The uptake of solvent into the skin may change the molecular organization of skin lipids and proteins, which may in turn alter the protective skin barrier function. We herein examine the molecular effects of 10 different solvents on the outermost layer of skin, the stratum corneum (SC), using polarization transfer solid-state NMR on natural abundance 13C in intact SC. With this approach it is possible to characterize the molecular dynamics of solvent molecules when present inside intact SC and to simultaneously monitor the effects caused by the added solvent on SC lipids and protein components. All solvents investigated cause an increased fluidity of SC lipids, with the most prominent effects shown for the apolar hydrocarbon solvents and 2-propanol. However, no solvent other than water shows the ability to fluidize amino acids in the keratin filaments. The solvent molecules themselves show reduced molecular mobility when incorporated in the SC matrix. Changes in the molecular properties of the SC, and in particular alternation in the balance between solid and fluid SC components, may have significant influences on the macroscopic SC barrier properties as well as mechanical properties of the skin. Deepened understanding of molecular effects of foreign compounds in SC fluidity can therefore have strong impact on the development of skin products in pharmaceutical, cosmetic, and sanitary applications. PMID:28028209

How Sensitive Are Transdermal Transport Predictions by Microscopic Stratum Corneum Models to Geometric and Transport Parameter Input?

PubMed

Wen, Jessica; Koo, Soh Myoung; Lape, Nancy

2018-02-01

While predictive models of transdermal transport have the potential to reduce human and animal testing, microscopic stratum corneum (SC) model output is highly dependent on idealized SC geometry, transport pathway (transcellular vs. intercellular), and penetrant transport parameters (e.g., compound diffusivity in lipids). Most microscopic models are limited to a simple rectangular brick-and-mortar SC geometry and do not account for variability across delivery sites, hydration levels, and populations. In addition, these models rely on transport parameters obtained from pure theory, parameter fitting to match in vivo experiments, and time-intensive diffusion experiments for each compound. In this work, we develop a microscopic finite element model that allows us to probe model sensitivity to variations in geometry, transport pathway, and hydration level. Given the dearth of experimentally-validated transport data and the wide range in theoretically-predicted transport parameters, we examine the model's response to a variety of transport parameters reported in the literature. Results show that model predictions are strongly dependent on all aforementioned variations, resulting in order-of-magnitude differences in lag times and permeabilities for distinct structure, hydration, and parameter combinations. This work demonstrates that universally predictive models cannot fully succeed without employing experimentally verified transport parameters and individualized SC structures. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Investigation of cis-trans isomer dependent dermatotoxicokinetics of UV filter ethylhexyl methoxycinnamate through stratum corneum in vivo.

PubMed

Sharma, Anežka; Bányiová, Katarína; Vrana, Branislav; Justan, Ivan; Čupr, Pavel

2017-11-01

2-Ethylhexyl methoxycinnamate (EHMC) is one of the most used ultraviolet filters in personal care products. It undergoes cis/trans isomerization in sunlight, and there is limited toxicological understanding of the effects of the cis-isomer. It is known that two geometric isomers of one compound can have different physico-chemical properties and effects. However, there are no studies focusing on toxicokinetics of EHMC isomerization products to compare their potential difference in dermal exposure to cis-EHMC and trans-EHMC due to the difference in their dermatotoxicokinetics. In this study, dermal absorption of the parental trans-EHMC and its cis isomer was studied. A commercially available sunscreen lotion containing trans-EHMC and spiked with laboratory-prepared cis-EHMC was locally applied on the forearm skin of two volunteers. After 8 h of skin exposure, the stratum corneum (SC) layer was removed by tape stripping. The removed thickness of the SC was determined spectrophotometrically using a total protein assay. The concentration of both isomers in the removed SC was measured by HPLC-DAD. A new diffusion and permeability coefficient of both EHMC isomers in SC were determined by Fick's second law of diffusion in vivo. The difference in dermatotoxicokinetic parameters between the two isomers was not statistically significant. However, separate toxicological studies of isomeric forms and the determination of their dermatotoxicokinetic parameters are crucial for refinement of human risk assessment.

Quantification of free fatty acids in human stratum corneum using tandem mass spectrometry and surrogate analyte approach.

PubMed

Dapic, Irena; Kobetic, Renata; Brkljacic, Lidija; Kezic, Sanja; Jakasa, Ivone

2018-02-01

The free fatty acids (FFAs) are one of the major components of the lipids in the stratum corneum (SC), the uppermost layer of the skin. Relative composition of FFAs has been proposed as a biomarker of the skin barrier status in patients with atopic dermatitis (AD). Here, we developed an LC-ESI-MS/MS method for simultaneous quantification of a range of FFAs with long and very long chain length in the SC collected by adhesive tape (D-Squame). The method, based on derivatization with 2-bromo-1-methylpyridinium iodide and 3-carbinol-1-methylpyridinium iodide, allowed highly sensitive detection and quantification of FFAs using multiple reaction monitoring. For the quantification, we applied a surrogate analyte approach and internal standardization using isotope labeled derivatives of FFAs. Adhesive tapes showed the presence of several FFAs, which are also present in the SC, a problem encountered in previous studies. Therefore, the levels of FFAs in the SC were corrected using C12:0, which was present on the adhesive tape, but not detected in the SC. The method was applied to SC samples from patients with atopic dermatitis and healthy subjects. Quantification using multiple reaction monitoring allowed sufficient sensitivity to analyze FFAs of chain lengths C16-C28 in the SC collected on only one tape strip. Copyright © 2017 John Wiley & Sons, Ltd.

Retarder action of isosorbide in a microemulsion for a targeted delivery of ceramide NP into the stratum corneum.

PubMed

Steinbach, S C; Triani, R; Bennedsen, L; Gabel, A; Haeusler, O; Wohlrab, J; Neubert, R H H

2017-08-01

Ceramide [NP] is an integral component of the stratum corneum (SC) lipid matrix and is capable of forming tough and stable lamellar structures. It was proven, that in skin diseases as psoriasis or atopic dermatitis different ceramide (CER) classes, including [NP], are degraded. It is obvious that topically application of CER on impaired skin is useful for repairing the skin barrier but a tendency for low penetration due to its poor solubility in conventional dosage forms was observed. Therefore, a stable and physiologic compatible colloidal carrier system, a microemulsion (ME), was developed and characterized. The increasing knowledge of the new colloidal systems in this last decade shows their benefits in dermal application. Isosorbide (Polysorb P) was incorporated into the ME developed. It was expected that Polysorb P has a retarder potential in order to accumulate the CER in the SC, the outermost layer of the skin. Thereby the CER [NP] would be able to interact with the affected skin layers to strengthen the skin barrier. The release and penetration behavior of the CER [NP] from the ME was assessed ex vivo in a Franz diffusion cell. The results of the study showed that CER [NP] penetrate largely in the upper layers of the skin (from SC to stratum basale), which was the desired region. A recovery in the acceptor could not be detected that underlines an accumulation in upper layers. Furthermore, significantly increased values for the SC for the ME with retarder were not received. No differences in the concentrations of CER [NP] were observed. However, the toxicity of MEs was investigated using heńs egg test chorioallantoic membrane (HET-CAM). For the isosorbide-containing ME no difference was obtained in comparison to the non-containing. The results showed that both MEs are safe to be used on the skin for the controlled penetration of CER [NP] into the skin. The isosorbide had no effect on the irritating effect as well as on the penetration of the used CER.

Percutaneous absorption

PubMed Central

Brisson, Paul

1974-01-01

Clinical effectiveness of topically applied medications depends on the ability of the active ingredient to leave its vehicle and penetrate into the epidermis. The stratum corneum is that layer of the epidermis which functionally is the most important in limiting percutaneous absorption, showing the characteristics of a composite semipermeable membrane. A mathematical expression of transepidermal diffusion may be derived from Fick's Law of mass transport; factors altering the rate of diffusion are discussed. PMID:4597976

Drug Delivery Through the Skin: Molecular Simulations of Barrier Lipids to Design more Effective Noninvasive Dermal and Transdermal Delivery Systems for Small Molecules Biologics and Cosmetics

DOE Office of Scientific and Technical Information (OSTI.GOV)

J Torin Huzil; S Sivaloganathan; M Kohandel

The delivery of drugs through the skin provides a convenient route of administration that is often preferable to injection because it is noninvasive and can typically be self-administered. These two factors alone result in a significant reduction of medical complications and improvement in patient compliance. Unfortunately, a significant obstacle to dermal and transdermal drug delivery alike is the resilient barrier that the epidermal layers of the skin, primarily the stratum corneum, presents for the diffusion of exogenous chemical agents. Further advancement of transdermal drug delivery requires the development of novel delivery systems that are suitable for modern, macromolecular protein andmore » nucleotide therapeutic agents. Significant effort has already been devoted to obtain a functional understanding of the physical barrier properties imparted by the epidermis, specifically the membrane structures of the stratum corneum. However, structural observations of membrane systems are often hindered by low resolutions, making it difficult to resolve the molecular mechanisms related to interactions between lipids found within the stratum corneum. Several models describing the molecular diffusion of drug molecules through the stratum corneum have now been postulated, where chemical permeation enhancers are thought to disrupt the underlying lipid structure, resulting in enhanced permeability. Recent investigations using biphasic vesicles also suggested a possibility for novel mechanisms involving the formation of complex polymorphic lipid phases. In this review, we discuss the advantages and limitations of permeation-enhancing strategies and how computational simulations, at the atomic scale, coupled with physical observations can provide insight into the mechanisms of diffusion through the stratum corneum.« less

Epidermal-skin-test 1,000 (EST-1,000)--a new reconstructed epidermis for in vitro skin corrosivity testing.

PubMed

Hoffmann, J; Heisler, E; Karpinski, S; Losse, J; Thomas, D; Siefken, W; Ahr, H-J; Vohr, H-W; Fuchs, H W

2005-10-01

The determination of a possible corrosive or irritative potential of certain products and ingredients is necessary for their classification and labeling requirements. Reconstructed skin as a model system provides fundamental advantages to single cell culture testing and leads to promising results as shown by different validation studies (for review: Fentem, J.H., Botham, P.A., 2002. ECVAM's activities in validating alternative tests for skin corrosion and irritation. ATLA 30(Suppl. 2), 61-67). In this study we introduce our new reconstructed epidermis "Epidermal-Skin-Test" (EST-1,000). This fully grown epidermis consists of proliferating as well as differentiating keratinocytes. EST-1,000 shows a high comparability to normal human skin as shown by histological and immunohistochemical data. Characteristic markers (KI-67, CK 1/10/5/14, transglutaminase, collagen IV, involucrin, beta 1 integrin) can be identified easily. The main focus of this work was to characterize EST-1,000 especially with respect to its barrier function by testing several substances of known corrosive potential. Skin corrosion was detected by the cytotoxic effect of the substances on a reconstructed epidermis after short-term application to the stratum corneum. The effect was determined by standard MTT assay and accompanying histological analysis. Hence EST-1,000 shows a very high predictive potential and closes the gap between animal testing and the established full-thickness model Advanced-Skin-Test 2,000 (AST-2,000) (Noll, M., Merkle, M.-L., Kandsberger, M., Matthes, T., Fuchs, H., Graeve, T., 1999. Reconstructed human skin (AST-2,000) as a tool for pharmaco-toxicology. ATLA 27, 302).

Residual antimicrobial effect of chlorhexidine digluconate and octenidine dihydrochloride on reconstructed human epidermis.

PubMed

Müller, G; Langer, J; Siebert, J; Kramer, A

2014-01-01

The objective of the present investigation was to examine the residual antimicrobial activity after a topical exposure of reconstructed human epidermis (RHE) to equimolar solutions of either chlorhexidine digluconate (CHG, 0.144% w/v) or octenidine dihydrochloride (OCT, 0.1% w/v) for 15 min. RHE-associated antiseptic agents were more effective on Staphylococcus aureus than on Pseudomonas aeruginosa. S. aureus was not detected after 24 h of contact, which demonstrated a microbicidal efficacy of greater than 5-log10 reduction. In contrast, P. aeruginosa was reduced by approximately 2 log10 at the same incubation time, which parallels the growth of the initial inoculum. This result could be interpreted either as a microbiostatic effect or as an adherence of P. aeruginosa to a low positively charged surface. Small amounts of CHG and OCT can penetrate the stratum corneum. Using these antiseptic agents, the viability of keratinocytes was reduced to 65-75% of that of the untreated RHE control following 24 h incubation in the presence of test microorganisms. With consideration of antimicrobial activity and cytotoxic effect, OCT corresponds better to a biocompatible antiseptic agent than CHG. Copyright © 2013 S. Karger AG, Basel.

Sun-Induced Changes in Stratum Corneum Function Are Gender and Dose Dependent in a Chinese Population

PubMed Central

Liu, Z.; Fluhr, J.W.; Song, S.P.; Sun, Z.; Wang, H.; Shi, Y.J.; Elias, P.M.; Man, M.-Q.

2010-01-01

Previous studies have demonstrated that UVB radiation changes the epidermal permeability barrier and stratum corneum (SC) hydration. It is well known that sun exposure causes erythema, sunburn and melanoma. However, whether daily sun exposure alters SC integrity and epidermal permeability barrier function is largely unknown, especially in Chinese subjects. In the present study, we assess the SC integrity, SC hydration and epidermal permeability barrier function following various doses of sun exposure. A total of 258 subjects (124 males and 134 females) aged 18–50 years were enrolled. A multifunctional skin physiology monitor (Courage & Khazaka MPA5) was used to measure SC hydration and transepidermal water loss (TEWL) on the forearms. In males, basal TEWL was higher with higher doses of sun exposure than with lower doses and control, whereas in females, basal TEWL was higher with lower doses of sun exposure than with higher doses and control. In the group with higher doses of sun exposure, TEWL in females was significantly lower than that in males. The barrier recovery was faster in females than in males in both control and lower-dose groups. In both males and females, barrier recovery was delayed with higher doses of sun exposure. In males, sun exposure did not alter SC hydration, while in females SC hydration was lower with lower doses of sun exposure as compared with control and higher doses of sun exposure. These results demonstrated that sun-induced changes in SC function and SC hydration vary with gender and the extent of sun exposure. PMID:20571289

Properties of Skin in Chinese Infants: Developmental Changes in Ceramides and in Protein Secondary Structure of the Stratum Corneum

PubMed Central

Yuan, Chao; Zou, Ying; Xueqiu, Yao; Miyauchi, Yuki; Fujimura, Tsutomu; Kitahara, Takashi; Wang, Xuemin

2017-01-01

The properties of infant skin regarding its structure and stratum corneum (SC) properties during development compared to adult skin have been reported only for a few races and body sites. The aim of this study was to understand the developmental changes of skin properties in Chinese infants, focusing on SC ceramides and protein secondary structure, which are important for skin barrier function. Three body sites with distinct characteristics (cheeks, inner upper arms, and buttocks) were assessed. Sixty pairs of Chinese infants and their mothers were measured for SC hydration, transepidermal water loss, ceramide levels, sebum with an ester bond, and protein secondary structure of superficial SC. Skin hydration decreased with age at all body sites. TEWL was similar between the 2–12- and 13–24-month-old groups but was higher than the adult group at the buttocks and inner upper arms and was equal to the adult group at the cheeks. These differences coincided with differences in protein secondary structure. Ceramide and sebum levels were lower in the infant groups. We conclude that both the SC functions and the components of infant skin are still developing and are not fully adapted as in adult skin at each body site examined. PMID:29098152

Enhancement of skin radical scavenging activity and stratum corneum lipids after the application of a hyperforin-rich cream.

PubMed

Haag, S F; Tscherch, K; Arndt, S; Kleemann, A; Gersonde, I; Lademann, J; Rohn, S; Meinke, M C

2014-02-01

Hyperforin is well-known for its anti-inflammatory, anti-tumor, anti-bacterial, and antioxidant properties. The application of a hyperforin-rich verum cream could strengthen the skin barrier function by reducing radical formation and stabilizing stratum corneum lipids. Here, it was investigated whether topical treatment with a hyperforin-rich cream increases the radical protection of the skin during VIS/NIR irradiation. Skin lipid profile was investigated applying HPTLC on skin lipid extracts. Furthermore, the absorption- and scattering coefficients, which influence radical formation, were determined. 11 volunteers were included in this study. After a single cream application, VIS/NIR-induced radical formation could be completely inhibited by both verum and placebo showing an immediate protection. After an application period of 4weeks, radical formation could be significantly reduced by 45% following placebo application and 78% after verum application showing a long-term protection. Furthermore, the skin lipids in both verum and placebo groups increased directly after a single cream application but only significantly for ceramide [AP], [NP1], and squalene. After long-term cream application, concentration of cholesterol and the ceramides increased, but no significance was observed. These results indicate that regular application of the hyperforin-rich cream can reduce radical formation and can stabilize skin lipids, which are responsible for the barrier function. Copyright © 2013 Elsevier B.V. All rights reserved.

Cutaneous water loss and sphingolipids in the stratum corneum of house sparrows, Passer domesticus L., from desert and mesic environments as determined by reversed phase high-performance liquid chromatography coupled with atmospheric pressure photospray ionization mass spectrometry.

PubMed

Muñoz-Garcia, Agustí; Ro, Jennifer; Brown, Johnie C; Williams, Joseph B

2008-02-01

Because cutaneous water loss (CWL) represents half of total water loss in birds, selection to reduce CWL may be strong in desert birds. We previously found that CWL of house sparrows from a desert population was about 25% lower than that of individuals from a mesic environment. The stratum corneum (SC), the outer layer of the epidermis, serves as the primary barrier to water vapor diffusion through the skin. The avian SC is formed by layers of corneocytes embedded in a lipid matrix consisting of cholesterol, free fatty acids and two classes of sphingolipids, ceramides and cerebrosides. The SC of birds also serves a thermoregulatory function; high rates of CWL keep body temperatures under lethal limits in episodes of heat stress. In this study, we used high-performance liquid chromatography coupled with atmospheric pressure photoionization-mass spectrometry (HPLC/APPI-MS) to identify and quantify over 200 sphingolipids in the SC of house sparrows from desert and mesic populations. Principal components analysis (PCA) led to the hypotheses that sphingolipids in the SC of desert sparrows have longer carbon chains in the fatty acid moiety and are more polar than those found in mesic sparrows. We also tested the association between principal components and CWL in both populations. Our study suggested that a reduction in CWL found in desert sparrows was, in part, the result of modifications in chain length and polarity of the sphingolipids, changes that apparently determine the interactions of the lipid molecules within the SC.

Inhomogeneous Monte Carlo simulations of dermoscopic spectroscopy

NASA Astrophysics Data System (ADS)

Gareau, Daniel S.; Li, Ting; Jacques, Steven; Krueger, James

2012-03-01

Clinical skin-lesion diagnosis uses dermoscopy: 10X epiluminescence microscopy. Skin appearance ranges from black to white with shades of blue, red, gray and orange. Color is an important diagnostic criteria for diseases including melanoma. Melanin and blood content and distribution impact the diffuse spectral remittance (300-1000nm). Skin layers: immersion medium, stratum corneum, spinous epidermis, basal epidermis and dermis as well as laterally asymmetric features (eg. melanocytic invasion) were modeled in an inhomogeneous Monte Carlo model.

In vivo penetration of bare and lipid-coated silica nanoparticles across the human stratum corneum.

PubMed

Iannuccelli, Valentina; Bertelli, Davide; Romagnoli, Marcello; Scalia, Santo; Maretti, Eleonora; Sacchetti, Francesca; Leo, Eliana

2014-10-01

Skin penetration of silica nanoparticles (NP) currently used in pharmaceutical and cosmetic products is a topic of interest not only to evaluate their possible toxicity, but also to understand their behaviour upon contact with the skin and to exploit their potential positive effects in drug or cosmetic delivery field. Therefore, the present work aimed to elucidate the in vivo mechanism by which amorphous hydrophilic silica NP enter human stratum corneum (SC) through the evaluation of the role played by the nanoparticle surface polarity and the human hair follicle density. Two silica samples, bare hydrophilic silica (B-silica, 162±51nm in size) and hydrophobic lipid-coated silica (LC-silica, 363±74nm in size) were applied on both the volar and dorsal side of volunteer forearms. Twelve repetitive stripped tapes were removed from the human skin and evaluated for elemental composition by Energy Dispersive X-ray (EDX) analysis and for silicon content by Inductively Coupled Plasma quadrupole Mass Spectrometry (ICP-MS). All the stripped tapes revealed nanosized structures generally located in the broad spaces between corneocytes and characterized by the same elemental composition (relative weight percentage of silicon and silicon to oxygen weight ratio) than that of the applied samples. However, only about 10% B-silica permeated until the deepest SC layers considered in the study indicating a silica retention in the upper layers of SC, regardless of the hair follicle density. Otherwise, the exposure to LC-silica led to a greater silica skin penetration extent into the deeper SC layers (about 42% and 18% silica following volar and dorsal forearm application, respectively) indicating that the NP surface polarity played a predominant role on that of their size in determining the route and the extent of penetration. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of microgravity on epidermal development in the rat

NASA Technical Reports Server (NTRS)

Hoath, Steven B.

1995-01-01

The overall goal of this project was to investigate the effects of prolonged weightlessness on the development of the skin in the fetal and newborn rat. Specifically, we used the NASA microgravitational rat model to test the following hypotheses: (1) Exposure of the pregnant rat to microscopy during late gestation will diminish the transport of calcium across the placenta from the mother to the fetus leading to decreases in total epidermal and dermal calcium content; (2) Microgravity will lead to slowing of body growth and diminish the rate of formation of the outermost layer of the epidermis and the stratum corneum; and (3) Microgravity will lead to formation of a stratum corneum with decreased DC electrical resistance and increased permeability to tritiated water.

Determination of the influence of C24 D/(2R)- and L/(2S)-isomers of the CER[AP] on the lamellar structure of stratum corneum model systems using neutron diffraction.

PubMed

Schmitt, Thomas; Lange, Stefan; Sonnenberger, Stefan; Dobner, Bodo; Demé, Bruno; Neubert, Reinhard H H; Gooris, Gert; Bouwstra, Joke A

2017-12-01

This study was able to investigate the different influence of the d- and l-ceramide [AP] on the lamellar as well as molecular nanostructure of stratum corneum simulating lipid model mixtures. In this case, neutron diffraction together with specifically deuterated ceramide was used as an effective tool to investigate the lamellar and the molecular nanostructure of the mixtures. It could clearly be demonstrated, that both isomers show distinctly different characteristics, even though the variation between both is only a single differently arranged OH-group. The l-ceramide [AP] promotes a crystalline like phase behaviour even if mixed with ceramide [NP], cholesterol and free fatty acids. The d-ceramide [AP] only shows crystalline-like features if mixed only with cholesterol and free fatty acids but adopts a native-like behaviour if additionally mixed with ceramide [NP]. It furthermore demonstrates that the l-ceramide [AP] should not be used for any applications concerning ceramide substitution. It could however possibly serve its own purpose, if this crystalline like behaviour has some kind of positive influence on the SC or can be utilized for any practical applications. The results obtained in this study demonstrate that the diastereomers of ceramide [AP] are an attractive target for further research because their influence on the lamellar as well as the nanostructure is exceptionally strong. Additionally, the results furthermore show a very strong influence on hydration of the model membrane. With these properties, the d-ceramide [AP] could be effectively used to simulate native like behaviour even in very simple mixtures and could also have a strong impact on the native stratum corneum as well as high relevance for dermal ceramide substitution. The unnatural l-ceramide [AP] on the other hand should be investigated further, to assess its applicability. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of multiple light-scattering on TiO2 nanoparticles imbedded into stratum corneum on light transmittance in UV and visible wavelength regions

NASA Astrophysics Data System (ADS)

Popov, Alexey P.; Priezzhev, Alexander V.; Lademann, Jürgen; Myllylä, Risto

2007-05-01

This paper focuses on the simulation of propagation of radiation in UV and visible wavelength regions within a superficial skin layer (stratum corneum, SC) partially filled with titanium dioxide (TiO II) nanoparticles. Volume concentrations of the particles (0.67% - 2.25%) correspond to the maximal concentrations of the considered particles in the frames of independent scattering. Transmittance of 307-, 400-, and 500-nm light through a 20-μm thick SC is calculated. The effect of the TiO II nanoparticles on the contribution of photons undergone different numbers of scattering acts into transmittance is considered. It is shown that administration of the nanoparticles results in the broadening of the distribution of transmitted photons over undergone scattering acts. It also results in the shift of the maximum location of this distribution to larger number of scattering acts for the wavelengths of 400 and 500 nm being the latter the most pronounced. The increase of undergone scattering acts leads to the elongation of photon trajectories within the medium and results in the increase of the diffuse reflected light and the transmittance decrease.

Effect of detergents on the physicochemical properties of skin stratum corneum: a two-photon excitation fluorescence microscopy study.

PubMed

Bloksgaard, M; Brewer, J R; Pashkovski, E; Ananthapadmanabhan, K P; Sørensen, J A; Bagatolli, L A

2014-02-01

Understanding the structural and dynamical features of skin is critical for advancing innovation in personal care and drug discovery. Synthetic detergent mixtures used in commercially available body wash products are thought to be less aggressive towards the skin barrier when compared to conventional detergents. The aim of this work is to comparatively characterize the effect of a mild synthetic cleanser mixture (SCM) and sodium dodecyl sulphate (SDS) on the hydration state of the intercellular lipid matrix and on proton activity of excised skin stratum corneum (SC). Experiments were performed using two-photon excitation fluorescence microscopy. Fluorescent images of fluorescence reporters sensitive to proton activity and hydration of SC were obtained in excised skin and examined in the presence and absence of SCM and SDS detergents. Hydration of the intercellular lipid matrix to a depth of 10 μm into the SC was increased upon treatment with SCM, whereas SDS shows this effect only at the very surface of SC. The proton activity of SC remained unaffected by treatment with either detergent. While our study indicates that the SC is very resistant to external stimuli, it also shows that, in contrast to the response to SDS, SCM to some extent modulates the in-depth hydration properties of the intercellular lipid matrix within excised skin SC. © 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Evaluation of the molecular lipid organization in millimeter-sized stratum corneum by synchrotron X-ray diffraction.

PubMed

Suzuki, T; Uchino, T; Hatta, I; Miyazaki, Y; Kato, S; Sasaki, K; Kagawa, Y

2018-04-29

The aim of this study was to investigate whether the lamellar and lateral structure of intercellular lipid of stratum corneum (SC) can be evaluated from millimeter-sized SC (MSC) by X-ray diffraction. A 12 mm × 12 mm SC sheet from hairless mouse was divided into 16 pieces measuring 3 mm × 3 mm square. From another sheet, 4 pieces of ultramillimeter-sized SC (USC:1.5 mm × 1.5 mm square) were prepared. Small and wide-angle X-ray diffraction (SAXD and WAXD) measurements were performed on each piece. For MSC and USC, changes in the lamellar and lateral structure after the application of d-limonene were measured. The intensity of SAXD peaks due to the lamellar phase of long periodicity phase (LPP) and WAXD peaks due to the lateral hydrocarbon chain-packing structures varied in MSC and USC pieces, although over the 12 mm × 12 mm SC sheet. These results indicated that the intercellular lipid components and their proportion appeared nearly uniform. Application of d-limonene on MSC and USC piece with strong peaks in SAXD and the WAXD resulted in the disappearance of peaks due to the lamellar phase of LPP and decrease in peak intensity for the lateral hydrocarbon chain-packing structures. These changes are consistent with normal-sized sample results. We found that the selection of a sample piece with strong diffraction peaks due to the lamellar and lateral structure enabled evaluation of the SC structure in small-sized samples by X-ray diffraction. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Characterization of atopic skin and the effect of a hyperforin-rich cream by laser scanning microscopy.

PubMed

Meinke, Martina C; Richter, Heike; Kleemann, Anke; Lademann, Juergen; Tscherch, Kathrin; Rohn, Sascha; Schempp, Christoph M

2015-05-01

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease that affects both children and adults in an increasing manner. The treatment of AD often reduces subjective skin parameters, such as itching, dryness, and tension, but the inflammation cannot be cured. Laser scanning microscopy was used to investigate the skin surface, epidermal, and dermal characteristics of dry and atopic skin before and after treatment with an ointment rich in hyperforin, which is known for its anti-inflammatory effects. The results were compared to subjective parameters and transepidermal water loss, stratum corneum moisture, and stratum corneum lipids. Using biophysical methods, in particular laser scanning microscopy, it was found that atopic skin has distinct features compared to healthy skin. Treatment with a hyperforin-rich ointment resulted in an improvement of the stratum corneum moisture, skin surface dryness, skin lipids, and the subjective skin parameters, indicating that the barrier is stabilized and improved by the ointment. But in contrast to the improved skin surface, the inflammation in the deeper epidermis/dermis often continues to exist. This could be clearly shown by the reflectance confocal microscopy (RCM) measurements. Therefore, RCM measurements could be used to investigate the progress in treatment of atopic dermatitis.

Characterization of atopic skin and the effect of a hyperforin-rich cream by laser scanning microscopy

NASA Astrophysics Data System (ADS)

Meinke, Martina C.; Richter, Heike; Kleemann, Anke; Lademann, Juergen; Tscherch, Kathrin; Rohn, Sascha; Schempp, Christoph M.

2015-05-01

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease that affects both children and adults in an increasing manner. The treatment of AD often reduces subjective skin parameters, such as itching, dryness, and tension, but the inflammation cannot be cured. Laser scanning microscopy was used to investigate the skin surface, epidermal, and dermal characteristics of dry and atopic skin before and after treatment with an ointment rich in hyperforin, which is known for its anti-inflammatory effects. The results were compared to subjective parameters and transepidermal water loss, stratum corneum moisture, and stratum corneum lipids. Using biophysical methods, in particular laser scanning microscopy, it was found that atopic skin has distinct features compared to healthy skin. Treatment with a hyperforin-rich ointment resulted in an improvement of the stratum corneum moisture, skin surface dryness, skin lipids, and the subjective skin parameters, indicating that the barrier is stabilized and improved by the ointment. But in contrast to the improved skin surface, the inflammation in the deeper epidermis/dermis often continues to exist. This could be clearly shown by the reflectance confocal microscopy (RCM) measurements. Therefore, RCM measurements could be used to investigate the progress in treatment of atopic dermatitis.

Effect of menthone and related compounds on skin permeation of drugs with different lipophilicity and molecular organization of stratum corneum lipids.

PubMed

Lan, Yi; Wang, Jingyan; Li, Hui; Zhang, Yewen; Chen, Yanyan; Zhao, Bochen; Wu, Qing

2016-01-01

The objective of this article was to investigate the enhancing effect of menthone, menthol and pulegone on the transdermal absorption of drugs with different lipophilicity and probe their mechanisms of action at molecular level. Five model drugs, namely osthole, tetramethylpyrazine, ferulic acid, puerarin and geniposide, which were selected based on their lipophilicity denoted by logKo/w, were tested using in vitro permeation studies in which Franz diffusion cells and rat skin were employed. Infrared spectroscopy and molecular dynamic simulation were used to investigate the effect of these enhancers on the stratum corneum (SC) lipids, respectively. Three compounds could effectively promote the transdermal absorption of drugs with different lipophilicity, and the overall promoting capacities were in the following increasing order: pulegone < menthol < menthone. The penetration enhancement ratio was roughly in parabolic curve relationships with the drug lipophilicity after treatment with menthol or menthone, while the penetration enhancement effect of pulegone hardly changed with the alteration of the drug lipophilicity. The molecular mechanism studies suggested that menthone and menthol enhanced the skin permeability by disordering the ordered organization of SC lipids and extracted part of SC lipids, while pulegone appeared to promote drug transport across the skin only by extracting part of SC lipids.

Influence of niacinamide containing formulations on the molecular and biophysical properties of the stratum corneum.

PubMed

Mohammed, D; Crowther, J M; Matts, P J; Hadgraft, J; Lane, M E

2013-01-30

Niacinamide-containing moisturisers are known be efficacious in alleviating dry skin conditions and improving stratum corneum (SC) barrier function. However, the mechanisms of action of niacinamide at the molecular level in the SC are still not well understood. Previously, we have reported the development of novel methods to probe SC barrier properties in vivo. The aim of the present study was to characterise changes in Trans Epidermal Water Loss (TEWL), corneocyte surface area and maturity, selected protease activities and SC thickness after repeated application of a simple vehicle containing niacinamide. A commercial formulation was also included as a reference. The left and right mid-volar forearms of 20 healthy volunteers were used as study sites, to which topical formulations were applied twice daily for 28 days. After successive tape-stripping, corneocyte maturity and surface area were assessed. In addition, activity of the desquamatory kallikrein (KLK) protease enzymes KLK5 and KLK7, and tryptase and plasmin (implicated in inflammatory process) were measured using a fluorogenic probe assay. The amount of protein removed and TEWL were also recorded. SC thickness before and after treatment was determined using Confocal Raman Spectroscopy (CRS). Overall (i) corneocyte maturity and surface area decreased with increasing number of tape strips, (ii) activity of both the desquamatory and inflammatory enzymes was highest in the outer layers of the SC and decreased with depth (iii) TEWL increased as more SC layers were removed. Furthermore, areas treated with formulations containing niacinamide were significantly different to pre-treatment baseline and untreated/vehicle-control treated sites, with larger and more mature corneocytes, decreased inflammatory activity, decreased TEWL and increased SC thickness. These data (a) confirm the utility of measures and metrics developed previously for the non-invasive assay of SC barrier function, (b) present an holistic picture

Immediate and extended effects of sodium lauryl sulphate exposure on stratum corneum natural moisturizing factor.

PubMed

Hoffman, D R; Kroll, L M; Basehoar, A; Reece, B; Cunningham, C T; Koenig, D W

2014-02-01

Natural moisturizing factor (NMF) serves as the primary humectant of the stratum corneum (SC), principally comprised of hygroscopic amino acids and derivatives that absorb moisture. Barrier disruption has been shown to differentially affect the levels of specific NMF components, though the kinetics of NMF component restoration following disruption have not been examined. Here, we investigated the impact of barrier disruption caused by surfactant exposure on a subset of NMF components immediately following exposure and out to 10 days post-exposure. Volunteers wore patches containing either 1% w/v sodium lauryl sulphate (SLS) or distilled water on their forearms for 24 h. Measurements of transepidermal water loss, erythema, SC water content and a subset of SC NMF and lipid components were obtained at both sites before treatment, the day of patch removal, and 1, 2, 3, 6, and 10 days following treatment. Most measured NMF components decreased in response to SLS exposure. Exceptions were increases in lactate, ornithine and urea, and no difference in proline levels. In the days following exposure, reduced levels of several NMF components continued at the SLS site; however, all measured NMF components demonstrated equivalence to the vehicle control within 10 days. Histidine pH 7, lactate, ornithine and urea were the first to achieve levels equivalent to the vehicle control site, normalizing within 1 day after patch removal. Results imply that NMF components derived from sweat and urea cycling are least impacted by SLS exposure whereas NMF components derived from degradation of filaggrin and/or other S-100 proteins are most impacted. This implies the restoration of the processes responsible for S-100 protein processing into free amino acids takes several days to return to normal. Further examination of the enzymes involved in S-100 protein processing following barrier disruption would provide insight into the pathway(s) for NMF restoration during SC recovery. © 2013

Stratum corneum profiles of inflammatory mediators in patch test reactions to common contact allergens and sodium lauryl sulfate.

PubMed

Koppes, S A; Ljubojevic Hadzavdic, S; Jakasa, I; Franceschi, N; Jurakić Tončić, R; Marinović, B; Brans, R; Gibbs, S; Frings-Dresen, M H W; Rustemeyer, T; Kezic, S

2017-06-01

Recent studies have demonstrated allergen-specific differences in the gene expression of inflammatory mediators in patch tested skin. To determine levels of various inflammatory mediators in the stratum corneum (SC) after patch testing with common contact allergens and the skin irritant sodium lauryl sulfate (SLS). In total, 27 individuals who had previously patch tested positive to nickel, chromium, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) or para-phenylenediamine were retested and then patch tested with SLS and petrolatum, with petrolatum serving as the patch test control. At 72 h, the test sites were clinically graded and the SC samples collected on adhesive tape. The levels of 18 of the 32 quantified mediators differed significantly from that of the control patches for at least one of the tested substances. SLS and MCI/MI induced the largest number of immunomediators. Interleukin (IL)-16 levels were significantly higher in patch test reactions in all allergens than they were in the controls, while no significant difference was detected for SLS. Furthermore, a strong negative correlation was found between strength of patch test reaction and IL-1α levels. Cytokine profiles in the SC of patch tested skin did not show a distinct allergen-specific pattern. However, MCI/MI induced a larger and wider immune response than the other allergens, perhaps due to its potency as an irritant. The levels of IL-16 were significantly increased in patch test reactions to allergens but not to SLS; thus, they may help clinicians to differentiate between allergic contact dermatitis and irritant contact dermatitis. © 2016 British Association of Dermatologists.

Isolated human/animal stratum corneum as a partial model for 15 steps in percutaneous absorption: emphasizing decontamination, Part I.

PubMed

Hui, Xiaoying; Lamel, Sonia; Qiao, Peter; Maibach, Howard I

2013-03-01

Since the advent of World War II, governments and laboratories have made a concerted effort to improve prophylactic and therapeutic interventions counteracting cutaneously directed chemical warfare agents (CWA), and by inference, common industrial and consumer dermatotoxicants. In vitro percutaneous penetration assays, first utilized by Tregear in the 1940s and presently in various modifications, have been fundamental to this effort. Percutaneous penetration, often considered a simple one-step diffusion process, consists of at least 15 steps. The first part of this review covers the initial steps related to absorption and excretion kinetics, vehicle characteristics, and tissue disposition. Importantly, the partitioning behavior and stratum corneum (SC) diffusion by a wide physicochemical array of compounds shows that many compounds have similar diffusion coefficients determining their percutaneous absorption in vivo. After accounting for anatomical SC variation, the penetration flux value of a substance depends mainly on its SC/vehicle partition coefficient. Additionally, the SC acts as a 'reservoir' for topically applied molecules and application of tape stripping has been found to quantify the chemical remaining in the SC which can predict total molecular penetration in vivo. Decontamination is of particular concern and even expediting standard washing procedures after dermal chemical exposure often fails to remove chemicals. This overview summarizes knowledge of percutaneous penetration extending insights into the complexities of penetration, decontamination and potential newer assays that may be of practical importance. Copyright © 2012 John Wiley & Sons, Ltd.

Effect of borneol on the transdermal permeation of drugs with differing lipophilicity and molecular organization of stratum corneum lipids.

PubMed

Yi, Qi-Feng; Yan, Jin; Tang, Si-Yuan; Huang, Hui; Kang, Li-Yang

2016-01-01

The aim of the present paper was to investigate the promoting activity of borneol on the transdermal permeation of drugs with differing lipophilicity, and probe its alterations in molecular organization of stratum corneum (SC) lipids. The toxicity of borneol was evaluated in epidermal keratinocyte HaCaT and dermal fibroblast CCC-HSF-1 cell cultures and compared to known enhancers, and its irritant profile was also assessed by transepidermal water loss (TEWL) evaluation. The promoting effect of borneol on the transdermal permeation of five model drugs, namely 5-fluorouracil, antipyrine, aspirin, salicylic acid and ibuprofen, which were selected based on their lipophilicity denoted by logp value, were performed using in vitro skin permeation studies. Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) was employed to monitor the borneol-induced alteration in molecular organization of SC lipids. The enhancer borneol displayed lower cytotoxicity or irritation in comparison to the well-established and standard enhancer Azone. Borneol could effectively promote the transdermal permeation of five model drugs, and its enhancement ratios were found to be parabolic curve with the logp values of drugs, which exhibited the optimum permeation activity for relatively hydrophilic drugs (an estimated logp value of -0.5 ∼0.5). The molecular mechanism studies suggested that borneol could perturb the structure of SC lipid alkyl chains, and extract part of SC lipids, resulting in the alteration in the skin permeability barrier.

Skin fluorescence model based on the Monte Carlo technique

NASA Astrophysics Data System (ADS)

Churmakov, Dmitry Y.; Meglinski, Igor V.; Piletsky, Sergey A.; Greenhalgh, Douglas A.

2003-10-01

The novel Monte Carlo technique of simulation of spatial fluorescence distribution within the human skin is presented. The computational model of skin takes into account spatial distribution of fluorophores following the collagen fibers packing, whereas in epidermis and stratum corneum the distribution of fluorophores assumed to be homogeneous. The results of simulation suggest that distribution of auto-fluorescence is significantly suppressed in the NIR spectral region, while fluorescence of sensor layer embedded in epidermis is localized at the adjusted depth. The model is also able to simulate the skin fluorescence spectra.

Evaluation of skin surface hydration state and barrier function of stratum corneum of dorsa of hands and heels treated with PROTECT X2 skin protective cream.

PubMed

Kubota, Takahiro

2012-06-01

Skin roughness is a term commonly used in Japan to describe a poor skin condition related to a rough and dry skin surface that develops as a result of various damaging effects from the environment or skin inflammation. Recovery from skin roughness requires skin care for a long period, thus it is important to prevent development of such skin changes. PROTECT X2 contains agents used for a protective covering of the skin from frequent hand washing or use of alcohol-based disinfectants. These unique components are also thought to be effective to treat skin roughness of the dorsa of the hands and heels. In the present study, we evaluated the effectiveness of PROTECT X2 to increase skin surface hydration state, as well as enhance the barrier function of the stratum corneum of the dorsa of the hands and heels in elderly individuals. A total of 8 elderly subjects and their caretakers without any skin diseases participated in the study. They applied PROTECT X2 by themselves to the dorsum area of 1 hand and heel 3 to 5 times daily for 1 month, while the opposite sides were left untreated. We measured stratum corneum (SC) hydration and transepidermal water loss (TEWL) before beginning treatment, then 1 week and 1 month after the start of treatment to compare between the treated and untreated skin. SC hydration state after applications of PROTECT X2 was 1.5- to 3.0-fold higher than that of the untreated skin in the dorsa of both hands and heels, indicating that the moisturizing ingredients accompanied by water were replenished in those areas where the cream was applied. Also, TEWL in the dorsum of the hands was 17.0-27.9% lower on the treated side, indicating improvement in SC barrier function. On the basis of these findings, we concluded that PROTECT X2 enhances water-holding in the SC and aids the barrier function of the skin in the dorsum of the hands. In addition, we consider that this formulation is useful for not only protecting the hands from the effects of such agents

Animal models for transdermal drug delivery.

PubMed

Panchagnula, R; Stemmer, K; Ritschel, W A

1997-06-01

The purpose of this investigation was to compare the permeation characteristics of two different compounds (extremely polar and nonpolar), i.e., tritium-labeled water (W) and 14C-labeled 7-hydroxycoumarin (7-OHC), among 16 different species, including human skin. Snake skin exhibited highest permeability for both W and 7-OHC. Permeability and lag time values of W and 7-OHC across Brattleboro rat and hairless guinea pig are very close to human skin. Skin thickness in micrometers (full thickness, epidermis and stratum corneum, and stratum corneum), and number of hair follicles present in each cm2 were determined for each species. There was no relationship between number of hair follicles and permeability values for both W and 7-OHC. The skin thickness (full) was related to the relative permeability values of W, whereas for 7-OHC it was not.

Human axillary skin condition is improved following incorporation of glycerol into the stratum corneum from an antiperspirant formulation.

PubMed

Evans, Richard L; Turner, Graham A; Bates, Susan; Robinson, Teresa; Arnold, David; Marriott, Robert E; Pudney, Paul D A; Bonnist, Eleanor Y M; Green, Darren

2017-11-01

The study objectives were to demonstrate that glycerol, when topically applied from a roll-on antiperspirant formulation, can be delivered directly to human skin ex vivo and the axillary stratum corneum (SC) in vivo, and to assess whether it improves the quality of the axillary skin barrier. Ex vivo human skin absorption of glycerol was measured following application of a roll-on antiperspirant formulation containing 4% 13 C 3 -glycerol. Skin distribution of 13 C 3 -glycerol over 24 h was assessed using gas chromatography-mass spectrometry. In vivo axillary SC penetration was measured by confocal Raman spectroscopy and multivariate curve-resolution software 1 h after topical application of a roll-on antiperspirant formulation containing 8% deuterated glycerol (d 5 -glycerol). A clinical study was conducted to determine the efficacy of a roll-on antiperspirant formulation containing 4% glycerol in reducing shaving-induced visual irritation and in increasing axillary-skin hydration. Ex vivo skin absorption studies indicated that the formulation delivered 13 C 3 -glycerol into the SC at all timepoints over the 24-h period. In vivo Raman measurements (1 h after application) demonstrated that d 5 -glycerol was detectable to a depth of at least 10 μm in the axillary SC. Application of 4% glycerol from a roll-on antiperspirant formulation to the axilla was associated with significantly less visible irritation and greater skin hydration than observed with the control (glycerol-free) product. These studies demonstrate that glycerol, incorporated in a roll-on antiperspirant formulation, is delivered directly and rapidly to all depths of the axillary SC, and results in improvements in visible irritation and hydration in the axilla.

Molecular interactions of plant oil components with stratum corneum lipids correlate with clinical measures of skin barrier function

PubMed Central

Mack Correa, Mary Catherine; Mao, Guangru; Saad, Peter; Flach, Carol R; Mendelsohn, Richard; Walters, Russel M

2014-01-01

Plant-derived oils consisting of triglycerides and small amounts of free fatty acids (FFAs) are commonly used in skincare regimens. FFAs are known to disrupt skin barrier function. The objective of this study was to mechanistically study the effects of FFAs, triglycerides and their mixtures on skin barrier function. The effects of oleic acid (OA), glyceryl trioleate (GT) and OA/GT mixtures on skin barrier were assessed in vivo through measurement of transepidermal water loss (TEWL) and fluorescein dye penetration before and after a single application. OA's effects on stratum corneum (SC) lipid order in vivo were measured with infrared spectroscopy through application of perdeuterated OA (OA-d34). Studies of the interaction of OA and GT with skin lipids included imaging the distribution of OA-d34 and GT ex vivo with IR microspectroscopy and thermodynamic analysis of mixtures in aqueous monolayers. The oil mixtures increased both TEWL and fluorescein penetration 24 h after a single application in an OA dose-dependent manner, with the highest increase from treatment with pure OA. OA-d34 penetrated into skin and disordered SC lipids. Furthermore, the ex vivo IR imaging studies showed that OA-d34 permeated to the dermal/epidermal junction while GT remained in the SC. The monolayer experiments showed preferential interspecies interactions between OA and SC lipids, while the mixing between GT and SC lipids was not thermodynamically preferred. The FFA component of plant oils may disrupt skin barrier function. The affinity between plant oil components and SC lipids likely determines the extent of their penetration and clinically measurable effects on skin barrier functions. PMID:24372651

Effects of atmospheric relative humidity on Stratum Corneum structure at the molecular level: ex vivo Raman spectroscopy analysis.

PubMed

Vyumvuhore, Raoul; Tfayli, Ali; Duplan, Hélène; Delalleau, Alexandre; Manfait, Michel; Baillet-Guffroy, Arlette

2013-07-21

Skin hydration plays an important role in the optimal physical properties and physiological functions of the skin. Despite the advancements in the last decade, dry skin remains the most common characteristic of human skin disorders. Thus, it is important to understand the effect of hydration on Stratum Corneum (SC) components. In this respect, our interest consists in correlating the variations of unbound and bound water content in the SC with structural and organizational changes in lipids and proteins using a non-invasive technique: Raman spectroscopy. Raman spectra were acquired on human SC at different relative humidity (RH) levels (4-75%). The content of different types of water, bound and free, was measured using the second derivative and curve fitting of the Raman bands in the range of 3100-3700 cm(-1). Changes in lipidic order were evaluated using νC-C and νC-H. To analyze the effect of RH on the protein structure, we examined in the Amide I region, the Fermi doublet of tyrosine, and the νasymCH3 vibration. The contributions of totally bound water were found not to vary with humidity, while partially bound water varied with three different rates. Unbound water increased greatly when all sites for bound water were saturated. Lipid organization as well as protein deployment was found to be optimal at intermediate RH values (around 60%), which correspond to the maximum of SC water binding capacity. This analysis highlights the relationship between bound water, the SC barrier state and the protein structure and elucidates the optimal conditions. Moreover, our results showed that increased content of unbound water in the SC induces disorder in the structures of lipids and proteins.

Documentation of normal stratum corneum scaling in an average population: features of differences among age, ethnicity and body site.

PubMed

Chu, M; Kollias, N

2011-03-01

Scaling skin involves an imbalance between cell proliferation and desquamation, resulting in partially detached corneocytes at the stratum corneum (SC) surface that become visible as they scatter light. The purpose of this study was to document scaling skin with no associated pathology, to estimate the range of normal corneocyte detachment in the average population, and to determine if age, pigmentation and/or body sites of different exposures contribute to differences observed in the SC. Healthy African-American and Caucasian female subjects (n = 151) from a typical central New Jersey population, aged between 14 and 75 years, were evaluated on the dorsal forearm and upper inner arm. Dermatoscopy and adhesive tape were used to evaluate the appearance and adhesion of surface corneocytes. Transepidermal water loss and conductivity were measured to assess water-handling properties of the SC. Measurements were conducted during the winter. Corneocyte detachment observed with dermatoscopy became more prevalent with age and was more severe on the dorsal forearm and in Caucasian subjects. The distribution of the amount of corneocyte removal with adhesive tape increased with age. The range of values was larger in the dorsal forearm than the upper inner arm and was greater in Caucasian subjects than African-American subjects. Minimal changes were observed for water-handling properties. The architecture of the outer SC appears different between ages, body sites of different exposures, and individuals of different pigmentation groups, but minimal differences in water-handling properties are observed. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Effect of chemical permeation enhancers on stratum corneum barrier lipid organizational structure and interferon alpha permeability.

PubMed

Moghadam, Shadi H; Saliaj, Evi; Wettig, Shawn D; Dong, Chilbert; Ivanova, Marina V; Huzil, J Torin; Foldvari, Marianna

2013-06-03

The outermost layer of the skin, known as the stratum corneum (SC), is composed of dead corneocytes embedded in an intercellular lipid matrix consisting of ceramides, free fatty acids, and cholesterol. The high level of organization within this matrix protects the body by limiting the permeation of most compounds through the skin. While essential for its protective functions, the SC poses a significant barrier for the delivery of topically applied pharmaceutical agents. Chemical permeation enhancers (CPEs) can increase delivery of small drug compounds into the skin by interacting with the intercellular lipids through physical processes including extraction, fluidization, increased disorder, and phase separation. However, it is not clear whether these same mechanisms are involved in delivery of biotherapeutic macromolecules, such as proteins. Here we describe the effect of three categories of CPEs {solvents [ethanol, propylene glycol, diethylene glycol monoethyl ether (transcutol), oleic acid], terpenes [menthol, nerol, camphor, methyl salicylate], and surfactants [Tween 80, SDS, benzalkonium chloride, polyoxyl 40 hydrogenated castor oil (Cremophor RH40), didecyldimethylammonium bromide (DDAB), didecyltrimethylammonium bromide (DTAB)]} on the lipid organizational structure of human SC as determined by X-ray scattering studies. Small- and wide-angle X-ray scattering studies were conducted to correlate the degree of structural changes and hydrocarbon chain packing in SC lipids caused by these various classes of CPEs to the extent of permeation of interferon alpha-2b (IFNα), a 19 kDa protein drug, into human skin. With the exception of solvents, propylene glycol and ethanol, all classes of CPEs caused increased disordering of lamellar and lateral packing of lipids. We observed that the highest degree of SC lipid disordering was caused by surfactants (especially SDS, DDAB, and DTAB) followed by terpenes, such as nerol. Interestingly, in vitro skin permeation studies

The long periodicity phase (LPP) controversy part I: The influence of a natural-like ratio of the CER[EOS] analogue [EOS]-br in a CER[NP]/[AP] based stratum corneum modelling system: A neutron diffraction study.

PubMed

Schmitt, Thomas; Lange, Stefan; Sonnenberger, Stefan; Dobner, Bodo; Demé, Bruno; Langner, Andreas; Neubert, Reinhard H H

2018-06-18

This study used neutron diffraction to investigate a ceramide-[NP] C24/[AP] C24 /[EOS]-br C30/cholesterol/lignoceric acid (0.6: 0.3: 0.1: 0.7: 1) based stratum corneum modelling system. By adding specifically deuterated ceramides-[NP]-D 3 , [AP]-D 3 , and [EOS]-br-D 3 , detailed information on the lamellar and the nanostructure of the system was obtained. For the short periodicity phase a natural-like lamellar repeat distance of 5.47 ± 0.02 nm was observed, similar to the [NP]/[AP] base system without the [EOS]-br. Unlike in this system the ceramides here were slightly tilted, hinting towards a slightly less natural arrangement. Due to the deuteration it was possible to observe that the long ceramide chains were overlapping in the lamellar mid-plane. This is considered to be an important feature for the natural stratum corneum. Despite the presence of a ceramide [EOS] analogue - able to form a long phase arrangement - no distinct long periodicity phase was formed, despite a slightly higher than natural ω-acyl ceramide ratio of 10 mol%. The deuterated variant of this ceramide determined that the very long ceramide was integrated into the short periodicity phase, spanning multiple layers instead. The - compared to the base system - unchanged repeat distance highlights the stability of this structure. Furthermore, the localisation of the very long ceramide in the short periodicity phase indicates the possibility of a crosslinking effect and thus a multilayer stabilizing role for the ceramide [EOS]. It can be concluded, that additionally to the mere presence of ceramide-[EOS] more complex conditions have to be met in order to form this long phase. This has to be further investigated in the future. Copyright © 2018 Elsevier B.V. All rights reserved.

[Effects of Frankincense and Myrrh essential oil on transdermal absorption of ferulic acid in Chuanxiong].

PubMed

Guan, Yong-Mei; Tao, Ling; Zhu, Xiao-Fang; Zang, Zhen-Zhong; Jin, Chen; Chen, Li-Hua

2017-09-01

The aim of this paper was to explore the effects of Frankincense and Myrrh essential oil on transdermal absorption, and investigate the mechanism of permeation on the microstructure and molecular structure of stratum corneum. Through the determination of stratum corneum/medium partition coefficient of ferulicacid in Chuanxiong influenced by Frankincense and Myrrh essential oil, the effects of volatile oil of frankincense and Myrrh on the the microscopic and molecular structure of stratum corneum were explored by observation of skin stratum corneum structure under scanning electron microscopy, and investigation of frankincense and myrrh essential oil effects on the molecular structure of keratin and lipids in stratum corneum under Fourier transform infrared spectroscopy. The results showed that the oil could enhance the distribution of ferulic acid in the stratum corneum and medium, and to a certain extent damaged the imbricate structure of stratum corneum which was originally regularly, neatly, and closely arranged; some epidermal scales turned upward, with local peeling phenomenon. In addition, frankincense and myrrh essential oil caused the relative displacement of CH2 stretching vibration peak of stratum corneum lipids and amide stretching vibration peak of stratum corneum keratin, indicating that frankincense and myrrh essential oil may change the conformation of lipid and keratin in the stratum corneum, increase the bilayer liquidity of the stratum corneum lipid, and change the orderly and compact structure to increase the skin permeability and reduce the effect of barrier function. It can be concluded that Frankincense and Myrrh essential oil can promote the permeation effect by increasing the distribution of drugs in the stratum corneum and changing the structure of the stratum corneum. Copyright© by the Chinese Pharmaceutical Association.

Analysis of skin tissues spatial fluorescence distribution by the Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Y Churmakov, D.; Meglinski, I. V.; Piletsky, S. A.; Greenhalgh, D. A.

2003-07-01

A novel Monte Carlo technique of simulation of spatial fluorescence distribution within the human skin is presented. The computational model of skin takes into account the spatial distribution of fluorophores, which would arise due to the structure of collagen fibres, compared to the epidermis and stratum corneum where the distribution of fluorophores is assumed to be homogeneous. The results of simulation suggest that distribution of auto-fluorescence is significantly suppressed in the near-infrared spectral region, whereas the spatial distribution of fluorescence sources within a sensor layer embedded in the epidermis is localized at an `effective' depth.

Anatomy of the Skin and the Pathogenesis of Nonmelanoma Skin Cancer.

PubMed

Losquadro, William D

2017-08-01

Skin is composed of the epidermis, dermis, and adnexal structures. The epidermis is composed of 4 layers-the stratums basale, spinosum, granulosum, and corneum. The dermis is divided into a superficial papillary dermis and deeper reticular dermis. Collagen and elastin within the reticular dermis are responsible for skin tensile strength and elasticity, respectively. The 2 most common kinds of nonmelanoma skin cancers are basal cell and squamous cell carcinoma. Both are caused by a host of environmental and genetic factors, although UV light exposure is the single greatest predisposing factor. Copyright © 2017 Elsevier Inc. All rights reserved.

White piedra, black piedra, tinea versicolor, and tinea nigra: contribution to the diagnosis of superficial mycosis.

PubMed

Veasey, John Verrinder; Avila, Ricardo Bertozzi de; Miguel, Barbara Arruda Fraletti; Muramatu, Laura Hitomi

2017-01-01

Superficial mycoses are fungal infections restricted to the stratum corneum and to the hair shafts, with no penetration in the epidermis; they are: white piedra, black piedra, tinea versicolor, and tinea nigra. This study presents images of mycological tests performed in the laboratory, as well as exams performed at the authors office, in order to improve the dermatologist's knowledge about the diagnosis of these dermatoses, which are common in many countries.

An unsupervised machine learning method for delineating stratum corneum in reflectance confocal microscopy stacks of human skin in vivo

NASA Astrophysics Data System (ADS)

Bozkurt, Alican; Kose, Kivanc; Fox, Christi A.; Dy, Jennifer; Brooks, Dana H.; Rajadhyaksha, Milind

2016-02-01

Study of the stratum corneum (SC) in human skin is important for research in barrier structure and function, drug delivery, and water permeability of skin. The optical sectioning and high resolution of reflectance confocal microscopy (RCM) allows visual examination of SC non-invasively. Here, we present an unsupervised segmentation algorithm that can automatically delineate thickness of the SC in RCM images of human skin in-vivo. We mimic clinicians visual process by applying complex wavelet transform over non-overlapping local regions of size 16 x 16 μm called tiles, and analyze the textural changes in between consecutive tiles in axial (depth) direction. We use dual-tree complex wavelet transform to represent textural structures in each tile. This transform is almost shift-invariant, and directionally selective, which makes it highly efficient in texture representation. Using DT-CWT, we decompose each tile into 6 directional sub-bands with orientations in +/-15, 45, and 75 degrees and a low-pass band, which is the decimated version of the input. We apply 3 scales of decomposition by recursively transforming the low-pass bands and obtain 18 bands of different directionality at different scales. We then calculate mean and variance of each band resulting in a feature vector of 36 entries. Feature vectors obtained for each stack of tiles in axial direction are then clustered using spectral clustering in order to detect the textural changes in depth direction. Testing on a set of 15 RCM stacks produced a mean error of 5.45+/-1.32 μm, compared to the "ground truth" segmentation provided by a clinical expert reader.

Effect of Exercise-induced Sweating on facial sebum, stratum corneum hydration, and skin surface pH in normal population.

PubMed

Wang, Siyu; Zhang, Guirong; Meng, Huimin; Li, Li

2013-02-01

Evidence demonstrated that sweat was an important factor affecting skin physiological properties. We intended to assess the effects of exercise-induced sweating on the sebum, stratum corneum (SC) hydration and skin surface pH of facial skin. 102 subjects (aged 5-60, divided into five groups) were enrolled to be measured by a combination device called 'Derma Unit SSC3' in their frontal and zygomatic regions when they were in a resting state (RS), at the beginning of sweating (BS), during excessive sweating (ES) and an hour after sweating (AS), respectively. Compared to the RS, SC hydration in both regions increased at the BS or during ES, and sebum increased at the BS but lower during ES. Compared to during ES, Sebum increased in AS but lower than RS. Compared to the RS, pH decreased in both regions at the BS in the majority of groups, and increased in frontal region during ES and in zygomatic region in the AS. There was an increase in pH in both regions during ES in the majority of groups compared to the BS, but a decrease in the AS compared to during ES. The study implies that even in summer, after we sweat excessively, lipid products should be applied locally in order to maintain stability of the barrier function of the SC. The study suggests that after a short term(1 h or less) of self adjustment, excessive sweat from moderate exercise will not impair the primary acidic surface pH of the facial skin. Exercise-induced sweating significantly affected the skin physiological properties of facial region. © 2012 John Wiley & Sons A/S.

The morphologic changes in lamellar bodies and intercorneocyte lipids after tape stripping and occlusion with a water vapor-impermeable membrane.

PubMed

Jiang, S; Koo, S W; Lee, S H

1998-03-01

It has been reported that artificial restoration of barrier function by a water vapor-impermeable membrane after tape stripping induces barrier abrogation in hairless mice, impeding rather than enhancing barrier recovery. To address this issue, we examined the morphologic changes in the epidermis after tape stripping and occlusion with a water vapor-impermeable membrane in murine skin. Male hairless mice were used for all studies of barrier perturbation and occlusion. Barrier disruption was achieved by repeated application of cellophane tape. Immediately after tape stripping the animals were wrapped in a tightly fitting water vapor-impermeable membrane. Transepidermal water loss (TEWL) was measured 20 min after tape stripping and 14, 24, 36, 48 and 60 h after occlusion. For electron microscopy the samples were treated with osmium tetroxide (OsO4) or ruthenium tetroxide (RuO4). When tape-stripped animals were wrapped in a water vapor-impermeable membrane, thereby preventing water flux, barrier function did not recover normally. These results demonstrate that an artificial block to TEWL with an impermeable membrane did not enhance barrier recovery. By electron microscopy many transitional cells and lacunae of various sizes were seen within the intercellular spaces of the stratum corneum after occlusion following tape stripping. Occlusion also caused alterations in both lipid lamellar membrane structures in the stratum corneum interstices and the lamellar bodies in the cytosol of granulocytes and transitional cells. Secreted lamellar body contents also appeared to be abnormal in the stratum corneum-stratum granulosum junction.

In Vivo Multiphoton Microscopy for Investigating Biomechanical Properties of Human Skin.

PubMed

Liang, Xing; Graf, Benedikt W; Boppart, Stephen A

2011-06-01

The biomechanical properties of living cells depend on their molecular building blocks, and are important for maintaining structure and function in cells, the extracellular matrix, and tissues. These biomechanical properties and forces also shape and modify the cellular and extracellular structures under stress. While many studies have investigated the biomechanics of single cells or small populations of cells in culture, or the properties of organs and tissues, few studies have investigated the biomechanics of complex cell populations in vivo. With the use of advanced multiphoton microscopy to visualize in vivo cell populations in human skin, the biomechanical properties are investigated in a depth-dependent manner in the stratum corneum and epidermis using quasi-static mechanical deformations. A 2D elastic registration algorithm was used to analyze the images before and after deformation to determine displacements in different skin layers. In this feasibility study, the images and results from one human subject demonstrate the potential of the technique for revealing differences in elastic properties between the stratum corneum and the rest of the epidermis. This interrogational imaging methodology has the potential to enable a wide range of investigations for understanding how the biomechanical properties of in vivo cell populations influence function in health and disease.

Partial ablation of stratum corneum by UV (193-nm) or IR (2.94-μm) pulsed lasers to enhance transdermal drug delivery rate

NASA Astrophysics Data System (ADS)

Fujiwara, Ai; Hinokitani, Toshihiro; Goto, Kenichi; Arai, Tsunenori

2004-07-01

To develop the noninvasive transdermal drug delivery system, pulsed lasers (argon-fluoride excimer laser (ArF laser) and erbium:yittrium aluminum garnet laser (Er:YAG laser)) were used to partially ablate the stratum corneum (SC), the upper layer of the skin. Because of the barrier function of the SC to drug permeation, the number of drugs especially macromolecules used in transdermal drug delivery system without skin irritation has been limited. Ultrastructural changes on the SC surface of ablated Yucatan micropig skin in vitro were observed with Environmental Scanning Electron Microscope. The result indicated that the structural changes varied according to each laser sources and irradiation conditions (laser fluences and numbers of pulses). Many granular structures of about 2 μm in diameter were observed in the ablated sites on ArF laser with lower fluence exposure (30 mJ/cm2, 200 pulses), and plane structures in the sites with higher fluence exposure (80 mJ/cm2, 80 pulses). In contrast, the ablation of Er:YAG laser created some pores of about 20 μm across on the surface of the SC. Under the irradiation condition of partial ablation, the skin permeability of macromolecule compound was enhanced. This partial SC ablation by pulsed laser could be possible candidate of the noninvasive transdermal drug delivery system with good physiological conditions of skin.

White piedra, black piedra, tinea versicolor, and tinea nigra: contribution to the diagnosis of superficial mycosis*

PubMed Central

Veasey, John Verrinder; de Avila, Ricardo Bertozzi; Miguel, Barbara Arruda Fraletti; Muramatu, Laura Hitomi

2017-01-01

Superficial mycoses are fungal infections restricted to the stratum corneum and to the hair shafts, with no penetration in the epidermis; they are: white piedra, black piedra, tinea versicolor, and tinea nigra. This study presents images of mycological tests performed in the laboratory, as well as exams performed at the authors office, in order to improve the dermatologist's knowledge about the diagnosis of these dermatoses, which are common in many countries. PMID:29186263

A covalently cross-linked gel derived from the epidermis of the pilot whale Globicephala melas.

PubMed

Baum, C; Fleischer, L-G; Roessner, D; Meyer, W; Siebers, D

2002-01-01

The rheological properties of the stratum corneum of the pilot whale (Globicephala melas) were investigated with emphasis on their significance to the self-cleaning abilities of the skin surface smoothed by a jelly material enriched with various hydrolytic enzymes. The gel formation of the collected fluid was monitored by applying periodic-harmonic oscillating loads using a stress-controlled rheometer. In the mechanical spectrum of the gel, the plateau region of the storage modulus G' (<1200 Pa) and the loss modulus G" (>120 Pa) were independent of frequency (omega = 43.98 to 0.13 rad x s(-1), tau = 15 Pa, T = 20 degrees C), indicating high elastic performance of a covalently cross-linked viscoelastic solid. In addition, multi-angle laser light scattering experiments (MALLS) were performed to analyse the potential time-dependent changes in the weight-average molar mass of the samples. The observed increase showed that the gel formation is based on the assembly of covalently cross-linked aggregates. The viscoelastic properties and the shear resistance of the gel assure that the enzyme-containing jelly material smoothing the skin surface is not removed from the stratum corneum by shear regimes during dolphin jumping. The even skin surface is considered to be most important for the self-cleaning abilities of the dolphin skin against biofouling.

Isolated human and animal stratum corneum as a partial model for the 15 steps of percutaneous absorption: emphasizing decontamination, part II.

PubMed

Hui, Xiaoying; Lamel, Sonia; Qiao, Peter; Maibach, Howard I

2013-03-01

Cutaneously directed chemical warfare agents can elicit significant morbidity and mortality. The optimization of prophylactic and therapeutic interventions counteracting these agents is crucial, and the development of decontamination protocols and methodology of post dermal exposure risk assessments would be additionally applicable to common industrial and consumer dermatotoxicants. Percutaneous (PC) penetration is often considered a simple one-step diffusion process but presently consists of at least 15 steps. The systemic exposure to an agent depends on multiple factors and the second part of this review covers absorption and excretion kinetics, wash and rub effects, skin substantivity and transfer, among others. Importantly, the partitioning behavior and diffusion through the stratum corneum (SC) of a wide physicochemical array of compounds shows that many compounds have approximately the same diffusion coefficient which determines their percutaneous absorption in vivo. After accounting for anatomical variation of the SC, the penetration flux value of a substance depends mainly on its SC/vehicle partition coefficient. Additionally, the SC acts as a 'reservoir' for topically applied molecules, and tape stripping methodology can quantify the remaining chemical in the SC which can predict the total molecular penetration in vivo. The determination of ideal decontamination protocols is of utmost importance to reduce morbidity and mortality. However, even expeditious standard washing procedures post dermal chemical exposure often fails to remove chemicals. The second part of this overview continues to review percutaneous penetration extending insights into the complexities of penetration, decontamination and potential newer assays that may be of practical importance. Copyright © 2012 John Wiley & Sons, Ltd.

Changes in hydration of the stratum corneum are the most suitable indicator to evaluate the irritation of surfactants on the skin.

PubMed

Fujimura, T; Shimotoyodome, Y; Nishijima, T; Sugata, K; Taguchi, H; Moriwaki, S

2017-02-01

Irritancy levels of surfactants on human skin have not been clarified completely. The relationships between skin damage and changes of skin properties caused by various surfactants were investigated using non-invasive measurements. Aqueous solutions of seven kinds of anionic, non-ionic, and amphoteric surfactants were exposed to the inside of forearm skin of 20 human subjects in two separate studies using the cup method. Hydration of the stratum corneum (SC), transepidermal water loss (TEWL), pH, skin surface roughness, and contents of the SC were measured before and after one exposure and after five and nine consecutive exposures to various surfactants. The discontinuation ratio of subjects for testing in each surfactant was determined by skin irritation symptoms and was defined as the degree of skin damage. Significant changes were observed only in hydration, TEWL, and natural moisturizing factors (NMF) content in the SC following surfactant exposure. A significant correlation was observed between the discontinuation ratio of each surfactant and the changes of hydration, TEWL, and NMF. Especially, the change of SC hydration showed an excellent correlation with the discontinuation ratio both for single (r = 0.942, P < 0.001) and for chronic exposures (r = 0.934, P < 0.001). Our results indicate that the change of hydration of the SC is equivalent to the skin damage caused by surfactants, and therefore is the most suitable indicator to evaluate the irritation of surfactants on the skin. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

In vivo confocal Raman spectroscopy study of the vitamin A derivative perfusion through human skin

NASA Astrophysics Data System (ADS)

dos Santos, Laurita; Téllez Soto, Claudio A.; Favero, Priscila P.; Martin, Airton A.

2016-03-01

In vivo confocal Raman spectroscopy is a powerful non-invasive technique able to analyse the skin constituents. This technique was applied to transdermal perfusion studies of the vitamin A derivative in human skin. The composition of the stratum corneum (lipid bilayer) is decisive for the affinity and transport of the vitamin through skin. The vitamin A is significantly absorbed by human skin when applied with water in oil emulsion or hydro-alcoholic gel. The purpose of this study is to elucidate the behaviour of vitamin A derivative into human skin without the presence of enhancers. The results showed that the intensity band of the derivative (around 1600 cm-1), which represents the -C=O vibrational mode, was detected in different stratum corneum depths (up to 20 μm). This Raman peak of vitamin A derivative has non-coincident band with the Raman spectra of the skin epidermis, demonstrating that compound penetrated in forearm skin.

Infrared free electron laser enhanced transdermal drug delivery

NASA Astrophysics Data System (ADS)

Awazu, Kunio; Uchizono, Takeyuki; Suzuki, Sachiko; Yoshikawa, Kazushi

2005-08-01

It is necessary to control enhancement of transdermal drug delivery with non-invasive. The present study was investigated to assess the effectivity of enhancing the drug delivery by irradiating 6-μm region mid infrared free electron laser (MIR-FEL). The enhancement of transdermal drug (lidocaine) delivery of the samples (hairless mouse skin) irradiated with lasers was examined for flux (μg/cm2/h) and total penetration amount (μg/cm2) of lidocaine by High performance Liquid Chromatography (HPLC). The flux and total amount penatration date was enhanced 200-300 fold faster than the control date by the laser irradiation. FEL irradiating had the stratum corneum, and had the less thermal damage in epidermis. The effect of 6-μm region MIR-FEL has the enhancement of transdermal drug delivery without removing the stratum corneum because it has the less thermal damage. It leads to enhancement drug delivery system with non-invasive laser treatment.

Aconite poisoning following the percutaneous absorption of Aconitum alkaloids.

PubMed

Chan, Thomas Y K

2012-11-30

In vitro experiment using the modified Franz-type diffusion cell has demonstrated that the human skin is permeable to aconitine and mesaconitine. To characterise the risk of systemic toxicity following the topical applications of aconite tincture and raw aconite roots, relevant reports of percutaneous absorption of Aconitum alkaloids and aconite poisoning are reviewed. Published reports indicate that aconite tincture and raw aconite roots can be absorbed through the skin into systemic circulation to cause fatal and non-fatal aconite poisoning. Both aconite tincture and raw aconite roots contain very high concentrations of Aconitum alkaloids, which allow penetration of the stratum corneum along the diffusion gradient. The risk of systemic toxicity is even higher if Aconitum alkaloids are held in occlusive contact with the skin and the epidermis (stratum corneum) is already damaged. The public should be warned of the danger in using these topical aconite preparations and the risk of systemic toxicity following percutaneous absorption of Aconitum alkaloids. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

In-vivo dynamic characterization of microneedle skin penetration using optical coherence tomography

NASA Astrophysics Data System (ADS)

Enfield, Joey; O'Connell, Marie-Louise; Lawlor, Kate; Jonathan, Enock; O'Mahony, Conor; Leahy, Martin

2010-07-01

The use of microneedles as a method of circumventing the barrier properties of the stratum corneum is receiving much attention. Although skin disruption technologies and subsequent transdermal diffusion rates are being extensively studied, no accurate data on depth and closure kinetics of microneedle-induced skin pores are available, primarily due to the cumbersome techniques currently required for skin analysis. We report on the first use of optical coherence tomography technology to image microneedle penetration in real time and in vivo. We show that optical coherence tomography (OCT) can be used to painlessly measure stratum corneum and epidermis thickness, as well as microneedle penetration depth after microneedle insertion. Since OCT is a real-time, in-vivo, nondestructive technique, we also analyze skin healing characteristics and present quantitative data on micropore closure rate. Two locations (the volar forearm and dorsal aspect of the fingertip) have been assessed as suitable candidates for microneedle administration. The results illustrate the applicability of OCT analysis as a tool for microneedle-related skin characterization.

Role of lipids in the formation and maintenance of the cutaneous permeability barrier.

PubMed

Feingold, Kenneth R; Elias, Peter M

2014-03-01

The major function of the skin is to form a barrier between the internal milieu and the hostile external environment. A permeability barrier that prevents the loss of water and electrolytes is essential for life on land. The permeability barrier is mediated primarily by lipid enriched lamellar membranes that are localized to the extracellular spaces of the stratum corneum. These lipid enriched membranes have a unique structure and contain approximately 50% ceramides, 25% cholesterol, and 15% free fatty acids with very little phospholipid. Lamellar bodies, which are formed during the differentiation of keratinocytes, play a key role in delivering the lipids from the stratum granulosum cells into the extracellular spaces of the stratum corneum. Lamellar bodies contain predominantly glucosylceramides, phospholipids, and cholesterol and following the exocytosis of lamellar lipids into the extracellular space of the stratum corneum these precursor lipids are converted by beta glucocerebrosidase and phospholipases into the ceramides and fatty acids, which comprise the lamellar membranes. The lipids required for lamellar body formation are derived from de novo synthesis by keratinocytes and from extra-cutaneous sources. The lipid synthetic pathways and the regulation of these pathways are described in this review. In addition, the pathways for the uptake of extra-cutaneous lipids into keratinocytes are discussed. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. Published by Elsevier B.V.

Multiscale modeling of transdermal drug delivery

NASA Astrophysics Data System (ADS)

Rim, Jee Eun

2006-04-01

This study addresses the modeling of transdermal diffusion of drugs, to better understand the permeation of molecules through the skin, and especially the stratum corneum, which forms the main permeation barrier of the skin. In transdermal delivery of systemic drugs, the drugs diffuse from a patch placed on the skin through the epidermis to the underlying blood vessels. The epidermis is the outermost layer of the skin and can be further divided into the stratum corneum (SC) and the viable epidermis layers. The SC consists of keratinous cells (corneocytes) embedded in the lipid multi-bilayers of the intercellular space. It is widely accepted that the barrier properties of the skin mostly arises from the ordered structure of the lipid bilayers. The diffusion path, at least for lipophilic molecules, seems to be mainly through the lipid bilayers. Despite the advantages of transdermal drug delivery compared to other drug delivery routes such as oral dosing and injections, the low percutaneous permeability of most compounds is a major difficulty in the wide application of transdermal drug delivery. In fact, many transdermal drug formulations include one or more permeation enhancers that increase the permeation of the drug significantly. During the last two decades, many researchers have studied percutaneous absorption of drugs both experimentally and theoretically. However, many are based on pharmacokinetic compartmental models, in which steady or pseudo-steady state conditions are assumed, with constant diffusivity and partitioning for single component systems. This study presents a framework for studying the multi-component diffusion of drugs coupled with enhancers through the skin by considering the microstructure of the stratum corneum (SC). A multiscale framework of modeling the transdermal diffusion of molecules is presented, by first calculating the microscopic diffusion coefficient in the lipid bilayers of the SC using molecular dynamics (MD). Then a

Altered (/sup 125/I)epidermal growth factor binding and receptor distribution in psoriasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nanney, L.B.; Stoscheck, C.M.; Magid, M.

1986-03-01

Stimulation of growth and differentiation of human epidermis by epidermal growth factor (EGF) is mediated by its binding to specific receptors. Whether EGF receptors primarily mediate cell division or differentiation in hyperproliferative disease such as psoriasis vulgaris is unclear. To study the pathogenesis of psoriasis, 4-mm2 punch biopsy specimens of normal, uninvolved, and involved psoriatic skin were assayed for EGF receptors by autoradiographic, immunohistochemical, and biochemical methods. Using autoradiographic and immunohistochemical methods, basal keratinocytes were found to contain the greatest number of EGF binding sites and immunoreactive receptors as compared to the upper layers of the epidermis in both normalmore » epidermis and psoriatic skin. No EGF receptor differences between normal and psoriatic epidermis were observed in this layer. In the upper layers of the epidermis, a 2-fold increase in EGF binding capacity was observed in psoriatic skin as compared with normal thin or thick skin. Biochemical methods indicated that (/sup 125/I)EGF binding was increased in psoriatic epidermis as compared with similar thickness normal epidermis when measured on a protein basis. Epidermal growth factor was shown to increase phosphorylation of the EGF receptor in skin. EGF receptors retained in the nonmitotic stratum spinosum and parakeratotic stratum corneum may reflect the incomplete, abnormal differentiation that occurs in active psoriatic lesions. Alternatively, retained EGF receptors may play a direct role in inhibiting cellular differentiation in the suprabasal layers.« less

Characterization of silver particles in the stratum corneum of healthy subjects and atopic dermatitis patients dermally exposed to a silver-containing garment

PubMed Central

Bianco, Carlotta; Visser, Maaike J.; Pluut, Olivier A.; Svetličić, Vesna; Pletikapić, Galja; Jakasa, Ivone; Riethmuller, Christoph; Adami, Gianpiero; Filon, Francesca Larese; Schwegler-Berry, Diane; Stefaniak, Aleksandr B.; Kezic, Sanja

2018-01-01

Silver is increasingly being used in garments to exploit its antibacterial properties. Information on the presence of silver nanoparticles (AgNPs) in garments and their in vivo penetration across healthy and impaired skin from use is limited. We investigated the presence of AgNPs in a silver containing garment and in the stratum corneum (SC) of healthy subjects (CTRLs) and individuals with atopic dermatitis (AD). Seven CTRLs and seven AD patients wore a silver sleeve (13% Ag w/w) 8 h/day for five days on a forearm and a placebo sleeve on the other forearm. After five days, the layers of the SC were collected by adhesive tapes. The silver particles in the garment and SC were characterized by scanning electron microscopy with energy dispersive X-ray analysis (SEM-EDX) and atomic force microscopy (AFM). AFM and SEM revealed the presence of sub-micrometre particles having a broad range of sizes (30–500 nm) on the surface of the garment that were identified as silver. On the SC tapes collected from different depths, aggregates with a wide range of sizes (150 nm−2 μm) and morphologies were found. Most aggregates contained primarily silver, although some also contained chlorine and sulfur. There was no clear difference in the number or size of the aggregates observed in SC between healthy and AD subjects. After use, AgNPs and their aggregates were present in the SC at different depths of both healthy subjects and AD patients. Their micrometre size suggests that aggregation likely occurred in the SC. PMID:27647219

Controlled penetration of ceramides into and across the stratum corneum using various types of microemulsions and formulation associated toxicity studies.

PubMed

Sahle, Fitsum F; Wohlrab, Johannes; Neubert, Reinhard H H

2014-02-01

Several skin diseases such as psoriasis and atopic dermatitis are associated with the depletion or disturbance of stratum corneum (SC) lipids such as ceramides (CERs), free fatty acids and cholesterol. Studies suggested that replenishment of these lipids might help to treat diseased, affected or aged skin. With this premises in mind, there are some formulations in the market that contain SC lipids and currently, to facilitate permeation of the lipids deep into the SC, various CERs, and other SC lipid microemulsions (MEs) were developed and characterised using lecithin or TEGO® CARE PL 4 (TCPL4) as base surfactants. However, to date, there are no reports that involve the permeability of SC lipids into and across the SC, and therefore, the penetration of CER [NP] as a model ceramide from various formulations was investigated ex vivo using Franz diffusion cell. Besides, the toxicity of the MEs was assessed using hen's egg test chorioallantoic membrane (HET-CAM). The results of the study showed that CER [NP] could not permeate into deeper layers of the SC from a conventional hydrophilic cream. Unlike the cream, CER [NP] permeated into the deeper layers of the SC from both type of MEs, where permeation of the CER was more and into deeper layers from droplet type and lecithin-based MEs than bicontinuous (BC) type and TCPL4 based MEs, respectively. The CER also permeated into deeper layers from ME gels which was, however, shallow and to a lesser extent when compared with the MEs. The results of HET-CAM showed that both MEs are safe to be used topically, with lecithin-based MEs exhibiting better safety profiles than TCPL4 based MEs. Concluding, the study showed that the MEs are safe to be used on the skin for the controlled penetration of CER [NP] deep into the SC. Copyright © 2013 Elsevier B.V. All rights reserved.

In vitro percutaneous absorption studies and in vivo evaluation of anti-inflammatory activity of essential fatty acids (EFA) from fish oil extracts.

PubMed

Puglia, Carmelo; Tropea, Salvatore; Rizza, Luisa; Santagati, Natale Alfredo; Bonina, Francesco

2005-08-11

The aim of the present study was to evaluate the in vitro percutaneous absorption and the in vivo anti-inflammatory activity of EPA and DHA fatty acids from three oily extracts, obtained by acetonic extractions from the entrails of different varieties of Mediterranean fishes such as mackerel (Scomber scombrus), sardine (Sardina pilchardus) and horse mackerel (Trachurus mediterraneus). In the first part of our research, we focused our attention on the characterization of the oily extracts to determine their omega-3 polyunsaturated fatty acid content, then, we evaluated the in vitro percutaneous absorption through excised human skin (stratum corneum/epidermis membranes; SCE) of EPA and DHA contained in the extracts. In the second part, the fish oil which guaranteed the best in vitro permeation profile of these omega-3 fatty acids was studied in order to evaluate its inhibiting ability towards the in vivo UVB-induced skin erythema. From the results obtained, all the fish oils tested in this study presented significant amounts of omega-3 fatty acids EPA and DHA, and particularly sardine oil extract showed higher concentrations of these substances compared to the other two fish oils. The in vitro experiments revealed interesting fluxes of these compounds from sardine extract through the stratum corneum/epidermis membranes and an appreciable anti-inflammatory activity against UVB-induced erythema in human volunteers was also observed.

Assessment of metal sensitizer potency with the reconstructed human epidermis IL-18 assay.

PubMed

Gibbs, Susan; Kosten, Ilona; Veldhuizen, Rosalien; Spiekstra, Sander; Corsini, Emanuela; Roggen, Erwin; Rustemeyer, Thomas; Feilzer, Albert J; Kleverlaan, Cees J

2018-01-15

According to the new EU Medical Devices (MDR) legislation coming into effect in 2017, manufactures will have to comply with higher standards of quality and safety for medical devices in order to meet common safety concerns regarding such products. Metal alloys are extensively used in dentistry and medicine (e.g. orthopedic surgery and cardiology) even though clinical experience suggests that many metals are sensitizers. The aim of this study was to further test the applicability domain of the in vitro reconstructed human epidermis (RhE) IL-18 assay developed to identify contact allergens and in doing so: i) determine whether different metal salts, representing leachables from metal alloys used in medical devices, could be correctly labelled and classified; and ii) assess the ability of different salts for the same metal to penetrate the skin stratum corneum. Twenty eight chemicals including 15 metal salts were topically exposed to RhE. Nickel, chrome, gold, palladium were each tested in two different salt forms, and titanium in 4 different salt forms. Metal salts were labelled (YES/NO) as sensitizer if a threshold of more than 5 fold IL18 release was reached. The in vitro estimation of expected sensitization induction level (potency) was assessed by interpolating in vitro EC50 and IL-18 SI2 with LLNA EC3 and human NOEL values from standard reference curves generated using DNCB (extreme) and benzocaine (weak). Metal salts, in contrast to other chemical sensitizers and with the exception of potassium dichromate (VI) and cobalt (II) chloride, were not identified as contact allergens since they only induced a small or no increase in IL-18 production. This finding was not related to a lack of stratum corneum skin penetration since EC50 values (decrease in metabolic activity; MTT assay) were obtained after topical RhE exposure to 8 of the 15 metal salts. For nickel, gold and palladium salts, differences in EC50 values between two salts for the same metal could not be

Effect of flexing and massage on in vivo human skin penetration and toxicity of zinc oxide nanoparticles.

PubMed

Leite-Silva, Vânia R; Liu, David C; Sanchez, Washington Y; Studier, Hauke; Mohammed, Yousuf H; Holmes, Amy; Becker, Wolfgang; Grice, Jeffrey E; Benson, Heather Ae; Roberts, Michael S

2016-05-01

We assessed the effects of flexing and massage on human skin penetration and toxicity of topically applied coated and uncoated zinc oxide nanoparticles (˜75 nm) in vivo. Noninvasive multiphoton tomography with fluorescence lifetime imaging was used to evaluate the penetration of nanoparticles through the skin barrier and cellular apoptosis in the viable epidermis. All nanoparticles applied to skin with flexing and massage were retained in the stratum corneum or skin furrows. No significant penetration into the viable epidermis was seen and no cellular toxicity was detected. Exposure of normal in vivo human skin to these nanoparticles under common in-use conditions of flexing or massage is not associated with significant adverse events.

Atopic March from Atopic Dermatitis to Asthma-Like Lesions in NC/Nga Mice Is Accelerated or Aggravated by Neutralization of Stratum Corneum but Partially Inhibited by Acidification.

PubMed

Lee, Hae-Jin; Lee, Noo Ri; Jung, Minyoung; Kim, Dong Hye; Choi, Eung Ho

2015-12-01

Prolonged and/or repeated damage to the skin barrier followed by atopic dermatitis (AD) is an initial step in atopic march that ultimately progresses to respiratory allergy. Maintaining normal stratum corneum (SC) acidity has been suggested as a therapeutic or preventive strategy for barrier impairment caused by skin inflammation. We determined whether a representative AD murine model, NC/Nga mice, develops airway inflammation after repeated epicutaneous application followed by inhalation of house dust mite (HDM), implying atopic march, and whether prolongation of non-proper SC acidity accelerates respiratory allergy. HDM was applied to the skin of NC/Nga mice, accompanied by the application of neutral cream (pH 7.4) or acidic cream (pH 2.8) for 6 weeks. Intranasal inhalation of HDM was administered daily during the last 3 days. Repeated epicutaneous applications followed by inhalation of HDM in NC/Nga mice induced an atopic march-like progression from AD lesions to respiratory allergy. Concurrent neutral cream treatment accelerated or aggravated the allergic inflammation in the skin and respiratory system, whereas an acidic cream partially alleviated these symptoms. Collectively, we developed an atopic march in NC/Nga mice by HDM application, and found that prevention of a neutral environment in the SC may be an interventional method to inhibit the march.

Investigation of a CER[NP]- and [AP]-Based Stratum Corneum Modeling Membrane System: Using Specifically Deuterated CER Together with a Neutron Diffraction Approach.

PubMed

Schmitt, Thomas; Lange, Stefan; Dobner, Bodo; Sonnenberger, Stefan; Hauß, Thomas; Neubert, Reinhard H H

2018-01-30

Neutron diffraction was used as a tool to investigate the lamellar as well as molecular nanostructure of ceramide-[NP]/ceramide-[AP]/cholesterol/lignoceric acid model systems with a nativelike 2:1 ratio and a 1:2 ratio to study the influence of the ceramide-[AP]. By using mixtures together with cholesterol and free fatty acids as well as a humidity and temperature chamber while measuring, natural conditions were simulated as closely as possible. Despite its simplicity, the system simulated the native stratum corneum lipid matrix fairly closely, showing a similar lamellar thickness with a repeat distance of 5.45 ± 0.1 nm and a similar arrangement with overlapping long C24 chains. Furthermore, despite the very minor chemical difference between ceramide-[NP] and ceramide-[AP], which is only a single OH group, it was possible to demonstrate substantial differences between the structural influence of the two ceramides. Ceramide-[AP] could be concluded to be arranged in such a way that its C24 chain in both ratios is somehow shorter than that of ceramide-[NP], not overlapping as much with the opposite lamellar leaflet. Furthermore, in the unnatural 1:2 ratio, the higher ceramide-[AP] content causes an increased tilt of the ceramide acyl chains. This leads to even less overlapping within the lamellar midplane, whereas the repeat distance stays the same as for the ceramide-[NP]-rich system. In this nativelike 2:1 ratio, the chains are arranged mostly straight, and the long C24 chains show a broad overlapping region in the lamellar midplane.

Rapid, simultaneous and nanomolar determination of pyroglutamic acid and cis-/trans-urocanic acid in human stratum corneum by hydrophilic interaction liquid chromatography (HILIC)-electrospray ionization tandem mass spectrometry.

PubMed

Joo, Kyung-Mi; Han, Ji Yeon; Son, Eui Dong; Nam, Gae-Won; Chung, Han Young; Jeong, Hye-Jin; Cho, Jun-Cheol; Lim, Kyung-Min

2012-05-15

A rapid, sensitive and specific hydrophilic interaction liquid chromatography coupled to tandem mass spectrometric (HILIC-MS/MS) method for the simultaneous determination of pyroglutamic acid, cis- and trans-urocanic acid in human skin stratum corneum (SC) were developed and validated. This method was carried out without derivatization or addition of ion-pair additives in mobile phase. The analytes were extracted by PBS buffer solution and analyzed using an electrospray positive ionization mass spectrometry in the multiple reaction monitoring (MRM) mode. Chromatographic separation was performed on an AQUITY UPLC amide column using gradient elution with the mobile phase of water and acetonitrile. The standard curves were linear over the concentration range of 1.0-250 ng/mL with a correlation coefficient higher than 0.999 with an LLOQ of 0.5 ng/mL. The lower limits of detection (LLOD) of these analytes were lower than 0.2 ng/mL. The intra- and inter-day precisions were measured to be below 7.7% and accuracies were within the range of 94.3-102.6%. The validated method was successfully applied to determine the level of pyroglutamic acid and cis-/trans-urocanic acid in the SC samples from forearm and forehead region of 19 human volunteers. Copyright © 2012 Elsevier B.V. All rights reserved.

OCT analysis of microneedle and Er:YAG surface ablation for enhanced transdermal delivery of hyperosmotic agents for optical skin clearing

NASA Astrophysics Data System (ADS)

Stumpp, Oliver F.; Welch, A. J.; Gill, Harvinder S.; Prausnitz, Mark R.

2004-07-01

The purpose of this study is to investigate the feasibility of using microneedles in comparison to Er:YAG skin surface laser ablation as a means to modify the epidermis of in-vitro hamster skin to facilitate delivery of topically applied hyper-osmotics such as glycerol into the skin to achieve optical skin clearing. This allows to temporarily reduce scattering of light in otherwise turbid tissues with potential applications pertaining to non-invasive optical imaging techniques such as optical coherence tomography (OCT) or therapeutic applications like laser blood vessel coagulation to treat port wine stains in skin. A portable, battery powered Er:YAG laser (Lasette) manufactured by Cell Robotics Inc. was used to produce holes in the stratum corneum and epidermis using individual 400 μs pulses causing localized ablation. Following each laser pulse the tissue was mechanically translated by 1 mm before another pulse was delivered. As an alternative method to the use of an expensive laser source requiring some kind of light scanning mechanism to treat larger skin areas efficiently, microneedles were investigated. They do not require an energy supply, are also pain-free and can be manufactured into arrays allowing treatment of larger skin areas. A single application forms micron scale holes in the stratum corneum through which topically applied skin clearing agents such as glycerol can penetrate into the tissue. In this feasibility study individual microneedles were used to manually induce holes in the skin each spaced approximately 1 mm apart from the other. Upon such epidermal modification by either technique, glycerol was then applied to the tissue surface and amplitude OCT measurements monitored changes of the optical properties of the tissue over time. Due to the geometry of the microneedle used in this study the cross sectional area of each hole in the epidermis was about 68% smaller than the comparable ablation site caused by an individual laser pulse. Results

From contact angle titration to chemical force microscopy: a new route to assess the pH-dependent character of the stratum corneum.

PubMed

Wagner, Matthieu; Mavon, Alain; Haidara, Hamidou; Vallat, Marie-France; Duplan, Hélène; Roucoules, Vincent

2012-02-01

Despite of its complex multicomponent organization and its compact architecture, the Stratum corneum (SC) is not completely impermeable to substances directly applied on the skin surface. A huge number of works have been dedicated to the understanding of the mechanisms involved in substance permeation by exploring deeper layers than the SC itself. Surprisingly, there is a poor interest in studies relating to interactions which may occur in the near-surface region (i.e. approximately 1 nm depth) of the SC. In this work, equilibrium proton-transfer reactions have been used as probes to define in a fundamental point of view the nature of the SC interactions with its environment. Such titration curves are investigated on 'in vitro' SC (isolated SC from abdominal skin tissue) and on 'in vivo' volar forearm (a sebum poor area). The results are discussed in term of work of adhesion and surface pKa values. Because SC can 'reconstruct' under heating, influence of the temperature on titration curves is investigated and the role of the different components is discussed. Different sigmoidal transitions were observed. Two common pKa values (pKa(1) = 4 and pKa(2) = 11.5) were clearly identified in both cases and associated to an acid-base character. By playing with the temperature of 'in vitro' SC, the 'accessibility' of polar functions was increased, thus refining the results by revealing an amphoteric character with an acid-to-base transition at pH 3.5 and two acid transitions at pH = 6.5 and pH = 11.5. Adhesion forces between an Atomic Force Microscopy (AFM) tip and a single isolated corneocyte through buffered liquid media were also investigated to better understand the role of the individual corneocytes. © 2011 The Authors. ICS © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Reevaluation of the non-lesional dry skin in atopic dermatitis by acute barrier disruption: an abnormal permeability barrier homeostasis with defective processing to generate ceramide.

PubMed

Sugiura, Ayumi; Nomura, Tsuyoshi; Mizuno, Atsuko; Imokawa, Genji

2014-07-01

Atopic dermatitis is characterized by disruption of the cutaneous barrier due to reduced ceramide levels even in non-lesional dry skin. Following further acute barrier disruption by repeated tape strippings, we re-characterized the non-lesional dry skin of subjects with atopic dermatitis, which shows significantly reduced levels of barrier function and ceramide but not of beta-glucocerebrosidase activity. For the first time, we report an abnormal trans-epidermal water loss homeostasis in which delayed recovery kinetics of trans-epidermal water loss occurred on the first day during the 4 days after acute barrier disruption compared with healthy control skin. Interestingly, whereas the higher ceramide level in the stratum corneum of healthy control skin was further significantly up-regulated at 4 days post-tape stripping, the lower ceramide level in the stratum corneum of subjects with atopic dermatitis was not significantly changed. In a parallel study, whereas beta-glucocerebrosidase activity at 4 days post-tape stripping was significantly up-regulated in healthy control skin compared with before tape stripping, the level of that activity remained substantially unchanged in atopic dermatitis. These findings indicate that subjects with atopic dermatitis have a defect in sphingolipid-metabolic processing that generates ceramide in the interface between the stratum corneum and the epidermis. The results also support the notion that the continued disruption of barrier function in atopic dermatitis non-lesional skin is associated with the impaired homeostasis of a ceramide-generating process, which underscores an atopy-specific inflammation-triggered ceramide deficiency that is distinct from other types of dermatitis.

In-vivo morphologic and spectroscopic investigation of Psoriasis

NASA Astrophysics Data System (ADS)

Kapsokalyvas, Dimitrios; Cicchi, Riccardo; Bruscino, Nicola; Alfieri, Domenico; Massi, Daniela; Lotti, Torello; Pavone, Francesco S.

2011-07-01

Psoriasis is an autoimmune disease of the skin characterized by hyperkeratosis, hyperproliferation of the epidermis, inflammatory cell accumulation and increased dilatation of dermal papillary blood vessels. Cases of psoriasis were investigated in vivo with optical means in order to evaluate the potential of in vivo optical biopsy. A Polarization Multispectral Dermoscope was employed for the macroscopic observation. Features such as the 'dotted' blood vessels pattern was observed with high contrast. High resolution image sections of the epidermis and the dermis were produced with a custom made Multiphoton Microscope. Imaging extended from the surface of the lesion down to the papillary dermis, at a depth of 200 μm. In the epidermis, a characteristic morphology of the stratum corneum found only in Psoriasis was revealed. Additionally, the cytoplasmic area of the cells in the stratum spinosum layer was found to be smaller than normal. In the dermis the morphological features were more pronounced, where the elongated dermal papillae dominated the papillary layer. Their length exceeds 100μm, which is a far greater value compared to that of healthy skin. These in vivo observations are consistent with the ex vivo histopathological observations, supporting both the applicability and potentiality of multispectral dermoscopy and multiphoton microscopy in the field of in vivo optical investigation and biopsy of skin.

Laser-induced transepidermal elimination of dermal content by fractional photothermolysis

NASA Astrophysics Data System (ADS)

Hantash, Basil M.; Bedi, Vikramaditya P.; Sudireddy, Vasanthi; Struck, Steven K.; Herron, G. Scott; Chan, Kin Foong

2006-07-01

The wound healing process in skin is studied in human subjects treated with fractional photothermolysis. In-vivo histological evaluation of vacuoles formed over microthermal zones (MTZs) and their content is undertaken. A 30-W, 1550-nm single-mode fiber laser system delivers an array of 60 µm or 140 µm 1/e2 incidence microbeam spot size at variable pulse energy and density. Treatments span from 6 to 20 mJ with skin excisions performed 1-day post-treatment. Staining with hematoxylin and eosin demonstrates an intact stratum corneum with vacuolar formation within the epidermis. The re-epithelialization process with repopulation of melanocytes and keratinocytes at the basal layer is apparent by 1-day post-treatment. The dermal-epidermal (DE) junction is weakened and separated just above zones of dermal coagulation. Complete loss of dermal cell viability is noted within the confines of the MTZs 1-day post-treatment, as assessed by lactate dehydrogenase. All cells falling outside the irradiation field remain viable. Content within the epidermal vacuoles stain positively with Gomori trichrome, suggesting a dermal origin. However, the positive staining could be due to loss of specificity after thermal alteration. Nevertheless, this dermal extrusion hypothesis is supported by very specific positive staining with an antihuman elastin antibody. Fractional photothermolysis creates microthermal lesions that allow transport and extrusion of dermal content through a compromised DE junction. Some dermal material is incorporated into the microepidermal necrotic debris and shuttled up the epidermis to eventually be exfoliated through the stratum corneum. This is the first report of a nonablative laser-induced transport mechanism by which dermal content can be predictably extruded biologically through the epidermis. Thus, treatment with the 1550-nm fiber laser may provide the first therapeutic option for clinical indications, including pigmentary disorders such as medically

Genetic Algorithm for Opto-thermal Skin Hydration Depth Profiling Measurements

NASA Astrophysics Data System (ADS)

Cui, Y.; Xiao, Perry; Imhof, R. E.

2013-09-01

Stratum corneum is the outermost skin layer, and the water content in stratum corneum plays a key role in skin cosmetic properties as well as skin barrier functions. However, to measure the water content, especially the water concentration depth profile, within stratum corneum is very difficult. Opto-thermal emission radiometry, or OTTER, is a promising technique that can be used for such measurements. In this paper, a study on stratum corneum hydration depth profiling by using a genetic algorithm (GA) is presented. The pros and cons of a GA compared against other inverse algorithms such as neural networks, maximum entropy, conjugate gradient, and singular value decomposition will be discussed first. Then, it will be shown how to use existing knowledge to optimize a GA for analyzing the opto-thermal signals. Finally, these latest GA results on hydration depth profiling of stratum corneum under different conditions, as well as on the penetration profiles of externally applied solvents, will be shown.

Novel phytoceramides containing fatty acids of diverse chain lengths are better than a single C18-ceramide N-stearoyl phytosphingosine to improve the physiological properties of human stratum corneum.

PubMed

Oh, Myoung Jin; Cho, Young Hoon; Cha, So Yoon; Lee, Eun Ok; Kim, Jin Wook; Kim, Sun Ki; Park, Chang Seo

2017-01-01

Ceramides in the human stratum corneum (SC) are a mixture of diverse N -acylated fatty acids (FAs) with different chain lengths. C24 is the major class of FAs of ceramides. However, there are also other classes of ceramides with diverse chain lengths of FAs, and these lengths generally range from C16 to C26. This study aimed to prepare several types of phytoceramide containing diverse chain lengths of N -acylated FAs and compare them with C18-ceramide N -stearoyl phytosphingosine (NP) in terms of their effects on the physiological properties of the SC. We chose natural oils, such as horse fat oil, shea butter, sunflower oil, and a mixture of macadamia nut, shea butter, moringa, and meadowfoam seed oil, as sources of FAs and phytosphingosine as a sphingoid backbone to synthesize diverse phytoceramides. Each phytoceramide exhibited a distinctive formation of the lamellar structure, and their FA profiles were similar to those of their respective natural oil. The skin barrier properties, as analyzed in human skin, clearly demonstrated that all the phytoceramides improved the recovery rate of the damaged SC and enhanced hydration better than C18-ceramide NP did. In conclusion, natural oil-derived phytoceramides could represent a novel class of ceramides for cosmetic applications in the development of an ideal skin barrier moisturizer.

Novel phytoceramides containing fatty acids of diverse chain lengths are better than a single C18-ceramide N-stearoyl phytosphingosine to improve the physiological properties of human stratum corneum

PubMed Central

Oh, Myoung Jin; Cho, Young Hoon; Cha, So Yoon; Lee, Eun Ok; Kim, Jin Wook; Kim, Sun Ki; Park, Chang Seo

2017-01-01

Ceramides in the human stratum corneum (SC) are a mixture of diverse N-acylated fatty acids (FAs) with different chain lengths. C24 is the major class of FAs of ceramides. However, there are also other classes of ceramides with diverse chain lengths of FAs, and these lengths generally range from C16 to C26. This study aimed to prepare several types of phytoceramide containing diverse chain lengths of N-acylated FAs and compare them with C18-ceramide N-stearoyl phytosphingosine (NP) in terms of their effects on the physiological properties of the SC. We chose natural oils, such as horse fat oil, shea butter, sunflower oil, and a mixture of macadamia nut, shea butter, moringa, and meadowfoam seed oil, as sources of FAs and phytosphingosine as a sphingoid backbone to synthesize diverse phytoceramides. Each phytoceramide exhibited a distinctive formation of the lamellar structure, and their FA profiles were similar to those of their respective natural oil. The skin barrier properties, as analyzed in human skin, clearly demonstrated that all the phytoceramides improved the recovery rate of the damaged SC and enhanced hydration better than C18-ceramide NP did. In conclusion, natural oil-derived phytoceramides could represent a novel class of ceramides for cosmetic applications in the development of an ideal skin barrier moisturizer. PMID:28979153

Appearance benefits of skin moisturization.

PubMed

Jiang, Z-X; DeLaCruz, J

2011-02-01

Skin hydration is essential for skin health. Moisturized skin is generally regarded as healthy and healthy looking. It is thus speculated that there may be appearance benefits of skin moisturization. This means that there are corresponding changes in the optical properties when skin is moisturized. The appearance of the skin is the result of light reflection, scattering and absorption at various skin layers of the stratum corneum, epidermis, dermis and beyond. The appearance benefits of skin moisturization are likely primarily due to the changes in the optical properties of the stratum corneum. We hypothesize that the major optical effect of skin moisturization is the decrease of light scattering at the skin surface, i.e., the stratum corneum. This decrease of surface scattering corresponds to an increase of light penetration into the deeper layers of the skin. An experiment was conducted to measure the corresponding change in skin spectral reflectance, the skin scattering coefficient and skin translucency with a change in skin hydration. In the experiment, skin hydration was decreased with the topical application of acetone and alcohol and increased with the topical application of known moisturizers and occlusives such as PJ. It was found that both the skin spectral reflectance and the skin scattering coefficient increased when the skin was dehydrated and decreased when the skin was hydrated. Skin translucency increased as the skin became moisturized. The results agree with the hypothesis that there is less light scattering at the skin surface and more light penetration into the deeper skin layers when the skin is moisturized. As a result, the skin appears darker, more pinkish and more translucent. © 2010 John Wiley & Sons A/S.

Lowering relative humidity level increases epidermal protein deimination and drives human filaggrin breakdown.

PubMed

Cau, Laura; Pendaries, Valérie; Lhuillier, Emeline; Thompson, Paul R; Serre, Guy; Takahara, Hidenari; Méchin, Marie-Claire; Simon, Michel

2017-05-01

Deimination (also known as citrullination), the conversion of arginine in a protein to citrulline, is catalyzed by a family of enzymes called peptidylarginine deiminases (PADs). Three PADs are expressed in the epidermis, one of their targets being filaggrin. Filaggrin plays a central role in atopic dermatitis and is a key protein for the epidermal barrier. It aggregates keratins and is cross-linked to cornified envelopes. Following its deimination, it is totally degraded to release free amino acids, contributing to the natural moisturizing factor (NMF). The mechanisms controlling this multistep catabolism in human are unknown. To test whether external humidity plays a role, and investigate the molecular mechanisms involved. Specimens of reconstructed human epidermis (RHEs) produced in humid or dry conditions (>95% or 30-50% relative humidity) were compared. RHEs produced in the dry condition presented structural changes, including a thicker stratum corneum and a larger amount of keratohyalin granules. The transepidermal water loss and the stratum corneum pH were decreased whereas the quantity of NMF was greater. This highly suggested that filaggrin proteolysis was up-regulated. The expression/activity of the proteases involved in filaggrin breakdown did not increase while PAD1 expression and the deimination rate of proteins, including filaggrin, were drastically enhanced. Partial inhibition of PADs with Cl-amidine reversed the effect of dryness on filaggrin breakdown. These results demonstrate the importance of external humidity in the control of human filaggrin metabolism, and suggest that deimination plays a major role in this regulation. Copyright © 2017 Japanese Society for Investigative Dermatology. All rights reserved.

Topical delivery of a preformed photosensitizer for photodynamic therapy of cutaneous lesions

NASA Astrophysics Data System (ADS)

Oleinick, Nancy L.; Kenney, Malcolm E.; Lam, Minh; McCormick, Thomas; Cooper, Kevin D.; Baron, Elma D.

2012-02-01

Photosensitizers for photodynamic therapy (PDT) are most commonly delivered to patients or experimental animals via intravenous injection. After initial distribution throughout the body, there can be some preferential accumulation within tumors or other abnormal tissue in comparison to the surrounding normal tissue. In contrast, the photosensitizer precursor, 5-aminolevulinic acid (ALA) or one of its esters, is routinely administered topically, and more specifically, to target skin lesions. Following metabolic conversion to protoporphyrin IX, the target area is photoilluminated, limiting peripheral damage and targeting the effective agent to the desired region. However, not all skin lesions are responsive to ALA-PDT. Topical administration of fully formed photosensitizers is less common but is receiving increased attention, and some notable advances with selected approved and experimental photosensitizers have been published. Our team has examined topical administration of the phthalocyanine photosensitizer Pc 4 to mammalian (human, mouse, pig) skin. Pc 4 in a desired formulation and concentration was applied to the skin surface at a rate of 5-10 μL/cm2 and kept under occlusion. After various times, skin biopsies were examined by confocal microscopy, and fluorescence within regions of interest was quantified. Early after application, images show the majority of the Pc 4 fluorescence within the stratum corneum and upper epidermis. As a function of time and concentration, penetration of Pc 4 across the stratum corneum and into the epidermis and dermis was observed. The data indicate that Pc 4 can be delivered to skin for photodynamic activation and treatment of skin pathologies.

Changes in Transepidermal Water Loss and Skin Hydration according to Expression of Aquaporin-3 in Psoriasis

PubMed Central

Lee, Young; Je, Young-Jin; Lee, Sang-Sin; Li, Zheng Jun; Choi, Dae-Kyoung; Kwon, Yoo-Bin; Sohn, Kyung-Cheol; Im, Myung; Seo, Young Joon

2012-01-01

Background Aquaporins (AQPs) are a family of water transporting proteins present in many mammalian epithelial and endothelial cell types. Among the AQPs, AQP3 is known to be a water/glycerol transporter expressed in human skin. Objective The relationship between the expression level of AQP3 and transpidermal water loss (TEWL) in the lesional and peri-lesional skin of psoriasis-affected patients, and skin hydration in the lesional and peri-lesional skin of psoriasis patients, was investigated. Methods The expression of AQP3 in psoriasis-affected and healthy control skin was determined using immunohistochemical and immunofluroscence staining. TEWL and skin hydration were measured using a Tewameter® TM210 (Courage & Khazaka, Cologne, Germany) and a Corneometer® CM 820 (Courage & Khazaka), respectively. Results AQP3 was mainly expressed in the plasma membrane of stratum corneum and the stratum spinosum in normal epidermis. Unlike the normal epidermis, AQP3 showed decreased expression in the lesional and peri-lesional epidermis of psoriasis. TEWL was increased, and skin hydration was decreased, in the lesional and peri-lesional skin of psoriasis patients, compared with the healthy control sample. Conclusion Although various factors contribute to reduced skin hydration in the lesional and peri-lesional skin of psoriasis, AQP3 appears to be a key factor in the skin dehydration of psoriasis-affected skin. PMID:22577267

Inflammatory peeling skin syndrome caused a novel mutation in CDSN.

PubMed

Telem, Dana Fuchs; Israeli, Shirli; Sarig, Ofer; Sprecher, Eli

2012-04-01

Generalized peeling skin syndrome (PSS) is a rare autosomal recessive dermatosis manifesting with continuous exfoliation of the stratum corneum. The inflammatory (type B) subtype of PSS was recently found to be caused by deleterious mutations in the CDSN gene encoding corneodesmosin, a major component of desmosomal junctions in the uppermost layers of the epidermis. In the present study, we assessed a 10-month-old baby, who presented with generalized superficial peeling of the skin. Using PCR amplification and direct sequencing, we identified the third PSS-associated mutation in CDSN, a homozygous 4 bp duplication in the second exon of the gene (c.164_167dup GCCT; p.Thr57ProfsX6). These data further support the notion that corneodesmosin deficiency impairs cell-cell adhesion in the upper epidermis, paving the way for an abnormal inflammatory response due to epidermal barrier disruption.

Effect of different alcohols on stratum corneum kallikrein 5 and phospholipase A2 together with epidermal keratinocytes and skin irritation.

PubMed

Cartner, T; Brand, N; Tian, K; Saud, A; Carr, T; Stapleton, P; Lane, M E; Rawlings, A V

2017-04-01

The aim of this exploratory study was to investigate the effect of ethanol, isopropanol and n-propanol on stratum corneum (SC) enzymes and keratinocytes in vitro together with their effects on skin condition and function. Activities of kallikrein 5 (KLK5) and phospholipase A2 (PLA2) as well as keratinocyte metabolic activity, interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α) were measured in vitro in the presence and absence of the different alcohols. We also measured transepidermal water loss (TEWL), skin capacitance, visual dryness and visual redness on the volar forearms of 25 Caucasian women following application of the alcohols 20 and 100 times per day over a period of 14 days in a clinical study. Reduced activities of KLK5 and PLA2 were observed in the presence of the alcohols. The greatest denaturing effect was always observed for n-propanol (P < 0.001), and in the case of PLA2, the effect of isopropanol was greater than ethanol (P < 0.001). Equally, ethanol had the mildest effects on keratinocyte metabolic activity and cytokine secretion (P < 0.001) and n-propanol always produced the most severe changes in normal and differentiated keratinocytes. These in vitro findings supported the clinical results where the major effects were on the induction of skin irritation (increased dropout rates) and ranked the intolerance of the different alcohols as follows: n-propanol > isopropanol > ethanol. At the high application frequencies, the effect of the different alcohols on transepidermal water loss (TEWL) and skin capacitance was similar, but at the low application frequencies, n-propanol had a significant effect on TEWL and capacitance values (P < 0.05). Equally, n-propanol and isopropanol produced significantly more skin redness at the low application frequencies. Clearly, isopropanol and n-propanol caused significant SC and keratinocyte perturbation in vitro together with damage to skin condition and function in vivo whereas ethanol

Fatty acids are required for epidermal permeability barrier function.

PubMed

Mao-Qiang, M; Elias, P M; Feingold, K R

1993-08-01

The permeability barrier is mediated by a mixture of ceramides, sterols, and free fatty acids arranged as extracellular lamellar bilayers in the stratum corneum. Whereas prior studies have shown that cholesterol and ceramides are required for normal barrier function, definitive evidence for the importance of nonessential fatty acids is not available. To determine whether epidermal fatty acid synthesis also is required for barrier homeostasis, we applied 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), an inhibitor of acetyl CoA carboxylase, after disruption of the barrier by acetone or tape stripping. TOFA inhibits epidermal fatty acid by approximately 50% and significantly delays barrier recovery. Moreover, coadministration of palmitate with TOFA normalizes barrier recovery, indicating that the delay is due to a deficiency in bulk fatty acids. Furthermore, TOFA treatment also delays the return of lipids to the stratum corneum and results in abnormalities in the structure of lamellar bodies, the organelle which delivers lipid to the stratum corneum. In addition, the organization of secreted lamellar body material into lamellar bilayers within the stratum corneum interstices is disrupted by TOFA treatment. Finally, these abnormalities in lamellar body and stratum corneum membrane structure are corrected by coapplication of palmitate with TOFA. These results demonstrate a requirement for bulk fatty acids in barrier homeostasis. Thus, inhibiting the epidermal synthesis of any of the three key lipids that form the extracellular, lipid-enriched membranes of the stratum corneum results in an impairment in barrier homeostasis.

Fatty acids are required for epidermal permeability barrier function.

PubMed Central

Mao-Qiang, M; Elias, P M; Feingold, K R

1993-01-01

The permeability barrier is mediated by a mixture of ceramides, sterols, and free fatty acids arranged as extracellular lamellar bilayers in the stratum corneum. Whereas prior studies have shown that cholesterol and ceramides are required for normal barrier function, definitive evidence for the importance of nonessential fatty acids is not available. To determine whether epidermal fatty acid synthesis also is required for barrier homeostasis, we applied 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), an inhibitor of acetyl CoA carboxylase, after disruption of the barrier by acetone or tape stripping. TOFA inhibits epidermal fatty acid by approximately 50% and significantly delays barrier recovery. Moreover, coadministration of palmitate with TOFA normalizes barrier recovery, indicating that the delay is due to a deficiency in bulk fatty acids. Furthermore, TOFA treatment also delays the return of lipids to the stratum corneum and results in abnormalities in the structure of lamellar bodies, the organelle which delivers lipid to the stratum corneum. In addition, the organization of secreted lamellar body material into lamellar bilayers within the stratum corneum interstices is disrupted by TOFA treatment. Finally, these abnormalities in lamellar body and stratum corneum membrane structure are corrected by coapplication of palmitate with TOFA. These results demonstrate a requirement for bulk fatty acids in barrier homeostasis. Thus, inhibiting the epidermal synthesis of any of the three key lipids that form the extracellular, lipid-enriched membranes of the stratum corneum results in an impairment in barrier homeostasis. Images PMID:8102380

Investigation of the piezoelectric thimble tactile device operating modes.

PubMed

Bansevicius, Ramutis; Dragasius, Egidijus; Grigas, Vytautas; Jurenas, Vytautas; Mazeika, Darius; Zvironas, Arunas

2014-01-01

A multifunctional device to transfer graphical or text information for blind or visually impaired is presented. The prototype using tactile perception has been designed where information displayed on the screen of electronic device (mobile phone, PC) is transferred by oscillating needle, touching the fingertip. Having the aim to define optimal parameters of the fingertip excitation by needle, the computational analysis of different excitation modes has been carried out. A 3D solid computational finite element model of the skin segment, comprising four main fingertip skin layers (stratum corneum, epidermis, dermis and hypodermis) was built by using ANSYS Workbench FEA software. Harmonic analysis of its stress-strain state under excitation with different frequency (up to 10000 Hz) and harmonic force (0.01 N), acting outer stratum corneum layer in normal direction at one, two or three points has been performed. The influence of the mode of dynamic loading of skin was evaluated (in terms of the tactile signal level) on the basis of the normal and shear elastic strain in dermis, where mechanoreceptors are placed. It is shown that the tactile perception of information, delivered by three vibrating pins, may be influenced by configuration of excitation points (their number and phase of loading) and the frequency of excitation.

In vivo skin effects of a dimethylaminoethanol (DMAE) based formulation.

PubMed

Tadini, K A; Campos, P M B G Maia

2009-12-01

Dimethylaminoethanol (DMAE) has been used in anti-aging formulations but few scientifically based data address its efficacy. The aim of this study was to evaluate the effects of DMAE-based formulations on hairless mice and human skin. Formulations containing with or without DMAE were applied to the dorsum of hairless mice. Histopathological and histometric evaluations were carried out after seven days. Formulations were also applied to the ventral forearm and the lateral periocular area of human volunteers. Stratum corneum water content and skin mechanical properties were analyzed using Corneometer and Cutometer, before and after a single and repeated application. Histometric evaluations showed that formulations with or without DMAE increased the viable epidermis thickness, but only the DMAE-supplemented formulation led to increased dermal thickness. DMAE also induced increase in collagen fiber thickness, which was observed in the histopathological study. After the single and the 8-week period application on human skin, formulations with and without DMAE enhanced the stratum corneum water content in the forearm skin. Mechanical properties were not significantly modified. So, we can suggest that DMAE action is related to its effects on the dermis as observed in the histopathological and histometric studies and showed hydration effects on skin.

High resolution in-vivo imaging of skin with full field optical coherence tomography

NASA Astrophysics Data System (ADS)

Dalimier, E.; Bruhat, Alexis; Grieve, K.; Harms, F.; Martins, F.; Boccara, C.

2014-03-01

Full-field OCT (FFOCT) has the ability to provide en-face images with a very good axial sectioning as well as a very high transverse resolution (about 1 microns in all directions). Therefore it offers the possibility to visualize biological tissues with very high resolution both on the axial native view, and on vertical reconstructed sections. Here we investigated the potential dermatological applications of in-vivo skin imaging with FFOCT. A commercial FFOCT device was adapted for the in-vivo acquisition of stacks of images on the arm, hand and finger. Several subjects of different benign and pathological skin conditions were tested. The images allowed measurement of the stratum corneum and epidermis thicknesses, measurement of the stratum corneum refractive index, size measurement and count of the keratinocytes, visualization of the dermal-epidermal junction, and visualization of the melanin granules and of the melanocytes. Skins with different pigmentations could be discriminated and skin pathologies such as eczema could be identified. The very high resolution offered by FFOCT both on axial native images and vertical reconstructed sections allows for the visualization and measurement of a set of parameters useful for cosmetology and dermatology. In particular, FFOCT is a potential tool for the understanding and monitoring of skin hydration and pigmentation, as well as skin inflammation.

Biochemical enhancement of transdermal delivery with magainin peptide: modification of electrostatic interactions by changing pH.

PubMed

Kim, Yeu-Chun; Late, Sameer; Banga, Ajay K; Ludovice, Peter J; Prausnitz, Mark R

2008-10-01

Magainin is a naturally occurring, pore-forming peptide that has recently been shown to increase skin permeability. This study tested the hypothesis that electrostatic forces between magainin peptides and drugs mediate drug transport across the skin. Electrostatic interaction between positively charged magainin and a negatively charged model drug, fluorescein, was attractive at pH 7.4 and resulted in a 35-fold increase in delivery across human epidermis in vitro when formulated with 2% N-lauroylsarcosine in 50% ethanol. Increasing to pH 10 or 11 largely neutralized magainin's charge, which eliminated enhancement due to magainin. Shielding electrostatic interactions with 1-2M NaCl solution similarly eliminated enhancement. Showing the opposite dependence on pH, electrostatic interaction between magainin and a positively charged anti-nausea drug, granisetron, was largely neutralized at pH 10 and resulted in a 92-fold increase in transdermal delivery. Decreasing to pH 5 increased magainin's positive charge, which repelled granisetron and progressively decreased transdermal flux. Circular dichroism analysis, multi-photon microscopy, and FTIR spectroscopy showed no significant pH effect on magainin secondary structure, magainin deposition in stratum corneum, or stratum corneum lipid order, respectively. We conclude that magainin increases transdermal delivery by a mechanism involving electrostatic interaction between magainin peptides and drugs.

Cellular responses to disruption of the permeability barrier in a three-dimensional organotypic epidermal model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ajani, Gati; Sato, Nobuyuki; Mack, Judith A.

2007-08-15

Repeated injury to the stratum corneum of mammalian skin (caused by friction, soaps, or organic solvents) elicits hyperkeratosis and epidermal thickening. Functionally, these changes serve to restore the cutaneous barrier and protect the organism. To better understand the molecular and cellular basis of this response, we have engineered an in vitro model of acetone-induced injury using organotypic epidermal cultures. Rat epidermal keratinocytes (REKs), grown on a collagen raft in the absence of any feeder fibroblasts, developed all the hallmarks of a true epidermis including a well-formed cornified layer. To induce barrier injury, REK cultures were treated with intermittent 30-s exposuresmore » to acetone then were fixed and paraffin-sectioned. After two exposures, increased proliferation (Ki67 and BrdU staining) was observed in basal and suprabasal layers. After three exposures, proliferation became confined to localized buds in the basal layer and increased terminal differentiation was observed (compact hyperkeratosis of the stratum corneum, elevated levels of K10 and filaggrin, and heightened transglutaminase activity). Thus, barrier disruption causes epidermal hyperplasia and/or enhances differentiation, depending upon the extent and duration of injury. Given that no fibroblasts are present in the model, the ability to mount a hyperplastic response to barrier injury is an inherent property of keratinocytes.« less

Biochemical enhancement of transdermal delivery with magainin peptide: Modification of electrostatic interactions by changing pH

PubMed Central

Kim, Yeu-Chun; Late, Sameer; Banga, Ajay K.; Ludovice, Peter J.; Prausnitz, Mark R.

2008-01-01

Magainin is a naturally occurring, pore-forming peptide that has recently been shown to increase skin permeability. This study tested the hypothesis that electrostatic forces between magainin peptides and drugs mediate drug transport across the skin. Electrostatic interaction between positively charged magainin and a negatively charged model drug, fluorescein, was attractive at pH 7.4 and resulted in a 35 fold increase in delivery across human epidermis in vitro when formulated with 2% N-lauroylsarcosine in 50% ethanol. Increasing to pH 10 or 11 largely neutralized magainin’s charge, which eliminated enhancement due to magainin. Shielding electrostatic interactions with 1–2 M NaCl solution similarly eliminated enhancement. Showing the opposite dependence on pH, electrostatic interaction between magainin and a positively charged anti-nausea drug, granisetron, was largely neutralized at pH 10 and resulted in a 59 fold increase in transdermal delivery. Decreasing to pH 5 increased magainin’s positive charge, which repelled granisetron and progressively decreased transdermal flux. Circular dichroism analysis, multi-photon microscopy, and FTIR spectroscopy showed no significant pH effect on magainin secondary structure, magainin deposition in stratum corneum, or stratum corneum lipid order, respectively. We conclude that magainin increases transdermal delivery by a mechanism involving electrostatic interaction between magainin peptides and drugs. PMID:18601987

PBTK Modeling Demonstrates Contribution of Dermal and Inhalation Exposure Components to End-Exhaled Breath Concentrations of Naphthalene

PubMed Central

Kim, David; Andersen, Melvin E.; Chao, Yi-Chun E.; Egeghy, Peter P.; Rappaport, Stephen M.; Nylander-French, Leena A.

2007-01-01

Background Dermal and inhalation exposure to jet propulsion fuel 8 (JP-8) have been measured in a few occupational exposure studies. However, a quantitative understanding of the relationship between external exposures and end-exhaled air concentrations has not been described for occupational and environmental exposure scenarios. Objective Our goal was to construct a physiologically based toxicokinetic (PBTK) model that quantitatively describes the relative contribution of dermal and inhalation exposures to the end-exhaled air concentrations of naphthalene among U.S. Air Force personnel. Methods The PBTK model comprised five compartments representing the stratum corneum, viable epidermis, blood, fat, and other tissues. The parameters were optimized using exclusively human exposure and biological monitoring data. Results The optimized values of parameters for naphthalene were a) permeability coefficient for the stratum corneum 6.8 × 10−5 cm/hr, b) permeability coefficient for the viable epidermis 3.0 × 10−3 cm/hr, c) fat:blood partition coefficient 25.6, and d) other tissue:blood partition coefficient 5.2. The skin permeability coefficient was comparable to the values estimated from in vitro studies. Based on simulations of workers’ exposures to JP-8 during aircraft fuel-cell maintenance operations, the median relative contribution of dermal exposure to the end-exhaled breath concentration of naphthalene was 4% (10th percentile 1% and 90th percentile 11%). Conclusions PBTK modeling allowed contributions of the end-exhaled air concentration of naphthalene to be partitioned between dermal and inhalation routes of exposure. Further study of inter- and intraindividual variations in exposure assessment is required to better characterize the toxicokinetic behavior of JP-8 components after occupational and/or environmental exposures. PMID:17589597

PBTK modeling demonstrates contribution of dermal and inhalation exposure components to end-exhaled breath concentrations of naphthalene.

PubMed

Kim, David; Andersen, Melvin E; Chao, Yi-Chun E; Egeghy, Peter P; Rappaport, Stephen M; Nylander-French, Leena A

2007-06-01

Dermal and inhalation exposure to jet propulsion fuel 8 (JP-8) have been measured in a few occupational exposure studies. However, a quantitative understanding of the relationship between external exposures and end-exhaled air concentrations has not been described for occupational and environmental exposure scenarios. Our goal was to construct a physiologically based toxicokinetic (PBTK) model that quantitatively describes the relative contribution of dermal and inhalation exposures to the end-exhaled air concentrations of naphthalene among U.S. Air Force personnel. The PBTK model comprised five compartments representing the stratum corneum, viable epidermis, blood, fat, and other tissues. The parameters were optimized using exclusively human exposure and biological monitoring data. The optimized values of parameters for naphthalene were a) permeability coefficient for the stratum corneum 6.8 x 10(-5) cm/hr, b) permeability coefficient for the viable epidermis 3.0 x 10(-3) cm/hr, c) fat:blood partition coefficient 25.6, and d) other tissue:blood partition coefficient 5.2. The skin permeability coefficient was comparable to the values estimated from in vitro studies. Based on simulations of workers' exposures to JP-8 during aircraft fuel-cell maintenance operations, the median relative contribution of dermal exposure to the end-exhaled breath concentration of naphthalene was 4% (10th percentile 1% and 90th percentile 11%). PBTK modeling allowed contributions of the end-exhaled air concentration of naphthalene to be partitioned between dermal and inhalation routes of exposure. Further study of inter- and intraindividual variations in exposure assessment is required to better characterize the toxicokinetic behavior of JP-8 components after occupational and/or environmental exposures.

Penetration kinetics of dimethyl sulphoxide and glycerol in dynamic optical clearing of porcine skin tissue in vitro studied by Fourier transform infrared spectroscopic imaging.

PubMed

Jiang, Jingying; Boese, Matthias; Turner, Paul; Wang, Ruikang K

2008-01-01

By use of a Fourier transform infrared (FTIR) spectroscopic imaging technique, we examine the dynamic optical clearing processes occurring in hyperosmotically biocompatible agents penetrating into skin tissue in vitro. The sequential collection of images in a time series provides an opportunity to assess penetration kinetics of dimethyl sulphoxide (DMSO) and glycerol beneath the surface of skin tissue over time. From 2-D IR spectroscopic images and 3-D false color diagrams, we show that glycerol takes at least 30 min to finally penetrate the layer of epidermis, while DMSO can be detected in epidermis after only 4 min of being topically applied over stratum corneum sides of porcine skin. The results demonstrate the potential of a FTIR spectroscopic imaging technique as an analytical tool for the study of dynamic optical clearing effects when the bio-tissue is impregnated by hyperosmotically biocompatible agents such as glycerol and DMSO.

Visualization of drug distribution of topical minocycline in human facial skin with fluorescence microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hermsmeier, Maiko; Sawant, Tanvee; Lac, Diana; Yamamoto, Akira; Chen, Xin; Nagavarapu, Usha; Evans, Conor L.; Chan, Kin Foong

2017-02-01

Minocycline is an antibiotic regularly prescribed to treat acne vulgaris. The only commercially available minocycline comes in an oral dosage form, which often results in systemic adverse effects. A topical minocycline composition (BPX-01) was developed to provide localized and targeted delivery to the epidermis and pilosebaceous unit where acne-related bacteria, Propionibacterium acnes (P. acnes), reside. As minocycline is a known fluorophore, fluorescence microscopy was performed to investigate its potential use in visualizing minocycline distribution within tissues. BPX-01 with various concentrations of minocycline, was applied topically to freshly excised human facial skin specimens. Spatial distribution of minocycline and its fluorescence intensity within the stratum corneum, epidermis, dermis, and pilosebaceous unit were assessed. The resulting fluorescence intensity data as a function of minocycline concentration may indicate clinically relevant therapeutic doses of topical BPX-01 needed to kill P. acnes and reduce inflammation for successful clinical outcomes.

Er:YAG laser-induced changes in skin in vivo and transdermal drug delivery

NASA Astrophysics Data System (ADS)

Flock, Stephen T.; Stern, Tom; Lehman, Paul; Dinehart, Scott; Franz, Tom; Liu, George; Stern, Scott J.

1997-05-01

It has been shown that laser ablation of stratum corneum, in vitro, can result in an increased uptake of topically applied pharmaceuticals. We have performed measurements of drug permeation, using an in vitro model of human skin, that involves a portable Er:YAG laser used to ablate the stratum corneum. For the first time, this method of drug administration was tested in vivo in human volunteers, whereby a hydrocortisone blanching assay was used to assess the efficiency of the procedure. The results show that this is a safe and efficient way to ablate stratum corneum for the purpose of enhanced transcutaneous drug administration.

In vivo confocal Raman microscopic determination of depth profiles of the stratum corneum lipid organization influenced by application of various oils.

PubMed

Choe, ChunSik; Schleusener, Johannes; Lademann, Jürgen; Darvin, Maxim E

2017-08-01

The intercellular lipids (ICL) of stratum corneum (SC) play an important role in maintaining the skin barrier function. The lateral and lamellar packing order of ICL in SC is not homogenous, but rather depth-dependent. This study aimed to analyze the influence of the topically applied mineral-derived (paraffin and petrolatum) and plant-derived (almond oil and jojoba oil) oils on the depth-dependent ICL profile ordering of the SC in vivo. Confocal Raman microscopy (CRM), a unique tool to analyze the depth profile of the ICL structure non-invasively, is employed to investigate the interaction between oils and human SC in vivo. The results show that the response of SC to oils' permeation varies in the depths. All oils remain in the upper layers of the SC (0-20% of SC thickness) and show predominated differences of ICL ordering from intact skin. In these depths, skin treated with plant-derived oils shows more disordered lateral and lamellar packing order of ICL than intact skin (p<0.05). In the intermediate layers of SC (30-50% of SC thickness), the oils do not influence the lateral packing order of SC ICL (p>0.1), except plant-derived oils at the depth 30% of SC thickness. In the deeper layers of the SC (60-100% of SC thickness), no difference between ICL lateral packing order of the oil-treated and intact skin can be observed, except that at the depths of 70-90% of the SC thickness, where slight changes with more disorder states are measured for plant-derived oil treated skin (p<0.1), which could be explained by the penetration of free fatty acid fractions in the deep-located SC areas. Both oil types remain in the superficial layers of the SC (0-20% of the SC thickness). Skin treated with mineral- and plant-derived oils shows significantly higher disordered lateral and lamellar packing order of ICL in these layers of the SC compared to intact skin. Plant-derived oils significantly changed the ICL ordering in the depths of 30% and 70-90% of the SC thickness, which is

Variation of skin surface pH, sebum content and stratum corneum hydration with age and gender in a large Chinese population.

PubMed

Man, M Q; Xin, S J; Song, S P; Cho, S Y; Zhang, X J; Tu, C X; Feingold, K R; Elias, P M

2009-01-01

Evidence suggests the importance of skin biophysical properties in predicting diseases and in developing appropriate skin care. The results to date of studies on skin surface pH, stratum corneum (SC) hydration and sebum content in both genders and at various ages have been inconclusive, which was in part due to small sample size. Additionally, little is known about the skin physical properties of Asian, especially Chinese, subjects. In the present study, we assess the difference in skin surface pH, sebum content and SC hydration at various ages and in both genders in a large Chinese population without skin diseases. 713 subjects (328 males and 385 females) aged 0.5-94 years were enrolled in this study. The subjects were divided by age into 5 groups, i.e., 0-12, 13-35, 36-50, 51-70 and over 70 years old. A multifunctional skin physiology monitor was used to measure SC hydration, skin surface pH and sebum content on both the forehead and the forearms. In males, the highest sebum content was found on the forearm and the forehead in the age groups 36-50 (93.47 +/- 10.01 microg/cm(2)) and 51-70 years (9.16 +/- 1.95 microg/cm(2)), while in females, the highest sebum content was found on the forearm and the forehead in the age groups 13-35 (61.91 +/- 6.12 microg/cm(2)) and 51-70 years (7.54 +/- 2.55 microg/cm(2)). The forehead sebum content was higher in males aged 13-70 years than in age-matched females; the sebum content on the forehead in both males and females was higher than that on the forearm. Skin surface pH on the forehead of both males and females over the age of 70 years was higher than that in younger groups. SC hydration on the forehead in both males and females was lower above the age of 70, and the one in males aged 13-35 was higher than that in females (43.99 +/- 1.88 vs. 36.38 +/- 1.67 AU, p < 0.01). SC hydration on the forehead in both males and females did not significantly differ from that on the forearm. In a large Chinese cohort, the skin surface p

In-vivo optical investigation of psoriasis

NASA Astrophysics Data System (ADS)

Kapsokalyvas, Dimitrios; Cicchi, Riccardo; Bruscino, Nicola; Alfieri, Domenico; Massi, Daniela; Lotti, Torello; Pavone, Francesco S.

2011-03-01

Psoriasis is an autoimmune disease of the skin characterized by hyperkeratosis, hyperproliferation of the epidermis, inflammatory cell accumulation and increased dilatation of dermal papillary blood vessels. Cases of psoriasis were investigated in vivo with optical means in order to evaluate the potential of in vivo optical biopsy. A Polarization Multispectral Dermoscope was employed for the macroscopic observation. Features such as the 'dotted' blood vessels pattern was observed with high contrast. The average size of dot vessels in Psoriasis was measured to be 974 μm2 which is much higher compared to healthy skin. High resolution image sections of the epidermis and the dermis were produced with a custom made Multiphoton Microscope. Imaging extended from the surface of the lesion down to the papillary dermis, at a depth of 200 μm. In the epidermis, a characteristic morphology of the stratum corneum found only in Psoriasis was revealed. Additionally, the cytoplasmic area of the cells in the stratum spinosum layer was found to be smaller than normal. In the dermis the morphological features were more pronounced, where the elongated dermal papillae dominated the papillary layer. Their length exceeds 100μm, which is a far greater value compared to that of healthy skin. These in vivo observations are consistent with the ex vivo histopathological observations, supporting both the applicability and potentiality of multispectral dermoscopy and multiphoton microscopy in the field of in vivo optical investigation and biopsy of skin.

Stratum corneum lipid liposome-encapsulated panomycocin: preparation, characterization, and the determination of antimycotic efficacy against Candida spp. isolated from patients with vulvovaginitis in an in vitro human vaginal epithelium tissue model.

PubMed

İzgü, Fatih; Bayram, Günce; Tosun, Kübra; İzgü, Demet

2017-01-01

In this study, a liposomal lyophilized powder formulation of panomycocin was developed for therapeutic purposes against vulvovaginal candidiasis which affects 80% of women worldwide. Panomycocin is a potent antimycotic protein secreted by the yeast Wickerhamomyces anomalus NCYC 434. This study involved the preparation of panomycocin-loaded stratum corneum lipid liposomes (SCLLs), characterization of the SCLLs, and determination of antimycotic efficacy of the formulation against Candida albicans and Candida glabrata clinical vaginal isolates in a human vaginal epithelium tissue model. The encapsulation and loading efficiencies of SCLLs were 73% and 76.8%, respectively. In transmission electron microscopy images, the SCLLs appeared in the submicron size range. Dynamic light scattering analyses showed that the SCLLs had uniform size distribution. Zeta potential measurements revealed stable and positively charged SCLLs. In Fourier transform infrared spectroscopy analyses, no irreversible interactions between the encapsulated panomycocin and the SCLLs were detected. The SCLLs retained >98% of encapsulated panomycocin in aqueous solution up to 12 hours. The formulation was fungicidal at the same minimum fungicidal concentration values for non-formulated pure panomycocin when tested on an in vitro model of vaginal candidiasis. This is the first study in which SCLLs and a protein as an active ingredient have been utilized together in a formulation. The results obtained in this study led us to conduct further preclinical trials of this formulation for the development of an effective topical anti-candidal drug with improved safety.

Stratum corneum lipid liposome-encapsulated panomycocin: preparation, characterization, and the determination of antimycotic efficacy against Candida spp. isolated from patients with vulvovaginitis in an in vitro human vaginal epithelium tissue model

PubMed Central

İzgü, Fatih; Bayram, Günce; Tosun, Kübra; İzgü, Demet

2017-01-01

In this study, a liposomal lyophilized powder formulation of panomycocin was developed for therapeutic purposes against vulvovaginal candidiasis which affects 80% of women worldwide. Panomycocin is a potent antimycotic protein secreted by the yeast Wickerhamomyces anomalus NCYC 434. This study involved the preparation of panomycocin-loaded stratum corneum lipid liposomes (SCLLs), characterization of the SCLLs, and determination of antimycotic efficacy of the formulation against Candida albicans and Candida glabrata clinical vaginal isolates in a human vaginal epithelium tissue model. The encapsulation and loading efficiencies of SCLLs were 73% and 76.8%, respectively. In transmission electron microscopy images, the SCLLs appeared in the submicron size range. Dynamic light scattering analyses showed that the SCLLs had uniform size distribution. Zeta potential measurements revealed stable and positively charged SCLLs. In Fourier transform infrared spectroscopy analyses, no irreversible interactions between the encapsulated panomycocin and the SCLLs were detected. The SCLLs retained >98% of encapsulated panomycocin in aqueous solution up to 12 hours. The formulation was fungicidal at the same minimum fungicidal concentration values for non-formulated pure panomycocin when tested on an in vitro model of vaginal candidiasis. This is the first study in which SCLLs and a protein as an active ingredient have been utilized together in a formulation. The results obtained in this study led us to conduct further preclinical trials of this formulation for the development of an effective topical anti-candidal drug with improved safety. PMID:28831255

Quantification of skin penetration of antioxidants of varying lipophilicity.

PubMed

Abla, M J; Banga, A K

2013-02-01

Antioxidants play a vital role in protecting the skin from environmental distress. As the skin is constantly exposed to harmful UV radiation, endogenous antioxidants present in the superficial layers of the skin neutralize reactive oxygen species. Over time, antioxidants become depleted and loss their protective effect on the skin. Therefore, supplementing skin with topical antioxidant can help replenish this loss and fight the oxidative stress. The objective of this study was to deliver antioxidants topically and quantify the amount permeated in the stratum corneum and underlying skin. Polyphenols (catechin, resveratrol and curcumin) and vitamin (retinol) with various lipophilic properties were delivered via porcine ear skin, using propylene glycol as a vehicle. The amount in the stratum corneum and underlying skin was quantified using tape stripping and skin extraction methods, respectively, and samples were analysed via HPLC. All four antioxidants permeated into the skin from the propylene glycol vehicle. The order of the amount of antioxidant in the stratum corneum was catechin > resveratrol~ retinol> curcumin, whereas that in the underlying skin was retinol > catechin~ resveratrol~ curcumin. Of the total amount of polyphenols in the skin, approximately 90% was retained in the stratum corneum whereas 10% was quantified in the underlying skin. In contrast, 10% of retinol was retained in the stratum corneum whereas 90% permeated in the underlying skin. Polyphenols (catechin, resveratrol and curcumin) showed high concentration in the stratum corneum whereas retinol showed high accumulation in the underlying layers of the skin. © 2012 The Authors ICS © 2012 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Impact of the ceramide subspecies on the nanostructure of stratum corneum lipids using neutron scattering and molecular dynamics simulations. Part I: impact of CER[NS].

PubMed

Schmitt, Thomas; Gupta, Rakesh; Lange, Stefan; Sonnenberger, Stefan; Dobner, Bodo; Hauß, Thomas; Rai, Beena; Neubert, Reinhard H H

2018-05-30

For this study mixtures based on the ceramides [NS] (NS = non-hydroxy-sphingosine) and [AP] (AP = α-hydroxy-phytosphingosine) in a 2:1 and 1:2 ratio, together with cholesterol and lignoceric acid, were investigated. These mixtures are modelling the uppermost skin layer, the stratum corneum. Neutron diffraction, utilizing specifically deuterated ceramide molecules, was used to obtain a maximum amount of experimental detail. Highly detailed molecular dynamics simulations were used to generate even more information from the experimental data. It was possible to observe a single lamellar phase for both systems. They had a lamellar repeat distance of 5.43 ± 0.05 nm for the [NS]/[AP] 2:1 and a slightly shorter one of 5.34 ± 0.05 nm for the 1:2 system. The structure and water content was uninfluenced by excess humidity. Both the experimental and simulation data indicated slightly tilted ceramides, with their C24 chains overlapping in the lamellar mid-plane. This arrangement is well comparable to systems investigated before. The structure of both systems, except for the differing repeat distance, looks similar at first. However, on a smaller scale there were various distinct differences, demonstrating only low redundancy between the different ceramide species, despite only minor chemical differences. The mainly ceramide [AP] determined 1:2 system has a slightly smaller repeat distance. This is a result of a tighter arrangement of the lipids chain along the bilayer normal and increased overlapping of the long chains in the lamellar middle. For the CER[NS] some novel features could be shown, despite it being the overall most investigated ceramide. These include the low adaptability to changed lateral interactions, leading to an increased chain opening. This effect could explain its low miscibility with other lipids. The investigated model systems allows it to directly compare results from the literature which have used ceramide [NS] to the most recent

Dynamic characterization of hydrophobic and hydrophilic solutes in oleic-acid enhanced transdermal delivery using two-photon fluorescence microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tseng, Te-Yu; Yang, Chiu-Sheng; Chen, Yang-Fang

In this letter, we propose an efficient methodology of investigating dynamic properties of sulforhodamine B and rhodamine B hexyl ester molecules transporting across ex-vivo human stratum corneum with and without oleic acid enhancement. Three-dimensional, time-lapse fluorescence images of the stratum corneum can be obtained using two-photon fluorescence microscopy. Furthermore, temporal quantifications of transport enhancements in diffusion parameters can be achieved with the use of Fick's second law. Dynamic characterization of solutes transporting across the stratum corneum is an effective method for understanding transient phenomena in transdermal delivery of probe molecules, leading to improved delivery strategies of molecular species for therapeuticmore » purposes.« less

Mechanism of transdermal permeation promotion of lipophilic drugs by ethosomes.

PubMed

Yang, Li; Wu, Lifang; Wu, Dongze; Shi, Deshun; Wang, Tai; Zhu, Xiaoliang

2017-01-01

Ethosomes can promote the penetration of lipophilic drugs into the skin, but the underlying mechanism is still unknown. The purpose of this study was to investigate the mechanism of transdermal permeation promotion of lipophilic drugs by ethosomes. The formulation of ethosomes was optimized using the Box-Behnken experimental design, in which Rhodamine B and 1-palmitoyl-2-{12-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]dodecanoyl}- sn -glycero-3-phosphocholine were used to simulate a model lipophilic drug and act as a fluorescent tracer of ethosomal phospholipids, respectively. Liposomes with the same phospholipid concentration and a hydroethanolic solution with the same ethanol concentration were also prepared as controls. The percutaneous progression of the above fluorescent preparations was observed by confocal laser scanning microscopy, and the fluorescence intensity of the images was analyzed. The optimized ethosome formulation consisted of 2.45% yolk phospholipids, 30% ethanol, and 67.55% distilled water. The percutaneous permeation of Rhodamine B in the optimized ethosomes was superior to that in hydroethanolic solution ( P <0.05) and liposomes ( P <0.05). The ethosomes could penetrate the skin via the percutaneous pathway of the hair follicle and stratum corneum, while during the process of penetration, the vesicles were broken and the phospholipids were retained in the upper epidermis, with the test compounds penetrating gradually. The superior percutaneous penetration of ethosomes was linked to the synergistic effects of their ingredients. The percutaneous pathways of ethosomes included open hair follicles and stratum corneum pathways. In addition, the vesicles might break up during percutaneous penetration in the superficial layer of the skin, allowing the test compounds to keep permeating into the deeper layer alone, while the phospholipid was retained in the upper epidermis.

Using FLIM in the study of permeability barrier function of aged and young skin

NASA Astrophysics Data System (ADS)

Xu, P.; Choi, E. H.; Man, M. Q.; Crumrine, D.; Mauro, T.; Elias, P.

2006-02-01

Aged skin commonly is afflicted by inflammatory skin diseases or xerosis/eczema that can be triggered or exacerbated by impaired epidermal permeability barrier homeostasis. It has been previously described a permeability barrier defect in humans of advanced age (> 75 years), which in a murine analog >18 mos, could be attributed to reduced lipid synthesis synthesis. However, the functional abnormality in moderately aged mice is due not to decreased lipid synthesis, but rather to a specific defect in stratum corneum (SC) acidification causing impaired lipid processing processing. Endogenous Na +/H + antiporter (NHE1) level was found declined in moderately aged mouse epidermis. This acidification defect leads to perturbed permeability barrier homeostasis through more than one pathways, we addressed suboptimal activation of the essential, lipid-processing enzyme, β-glucocerebrosidase (BGC) is linked to elevated SC pH. Finally, the importance of the epidermis acidity is shown by the normalization of barrier function after exogenous acidification of moderately aged skin.

In vitro penetration through the skin layers of topically applied glucocorticoids.

PubMed

Carrer, Victor; Alonso, Cristina; Oliver, Marc Adrià; Coderch, Luisa

2018-05-22

Corticoids are actives widely used in the treatment of skin diseases. This work aims to study the penetration of three corticoids (betamethasone, clobetasol and flurandrenolide), their relationship with their Log D values and the effects of the vehicles. The three compounds were applied on a Franz-type diffusion cell in propylene glycol solution and their respective commercial creams and ointments. The active amounts found in the stratum corneum, epidermal and dermal layers of the skin were investigated. Their diffusions were greatly affected by the formulation, moreover higher amounts of substance in the epidermis and dermis were detected in ointments than in creams. The enhancement effect of propylene glycol was also observed. Moreover, the differences between the three substances could be related to their lipophilicity, molecular structure and molecular weight. The more hydrophobic compounds (clobetasol and betamethasone) are present in higher amounts in the epidermis and dermis, while the hydrophilic compound (flurandrenolide) is mostly present in the receptor fluid. This article is protected by copyright. All rights reserved.

A thermal microjet system with tapered micronozzles fabricated by inclined UV lithography for transdermal drug delivery

NASA Astrophysics Data System (ADS)

Yoon, Yong-Kyu; Park, Jung-Hwan; Lee, Jeong-Woo; Prausnitz, Mark R.; Allen, Mark G.

2011-02-01

Transdermal drug delivery can be enabled by various methods that increase the permeability of the skin's outer barrier of stratum corneum, including skin exposure to heat and chemical enhancers, such as ethanol. Combining these approaches for the first time, in this study we designed a microdevice consisting of an array of microchambers filled with ethanol that is vaporized using an integrated microheater and ejected through a micronozzle contacting the skin surface. In this way, we hypothesize that the hot ethanol vapor can increase skin permeability upon contacting the skin surface. The tapered micronozzle and the microchamber designed for this application were realized using proximity-mode inclined rotational ultraviolet lithography, which facilitates easy fabrication of complex three-dimensional structures, convenient integration with other functional layers, low fabrication cost, and mass production. The resulting device had a micronozzle with an orifice inner and outer diameter of 220 and 320 µm, respectively, and an extruded height of 250 µm. When the microchamber was filled with an ethanol gel and activated, the resulting ethanol vapor jet increased the permeability of human cadaver epidermis to a model compound, calcein, by approximately 17 times, which is attributed to thermal and chemical disruption of stratum corneum structure. This thermal microjet system can serve as a tool not only for transdermal drug delivery, but also for a variety of biomedical applications.

Keratin-lipid structural organization in the corneous layer of snake.

PubMed

Ripamonti, Alberto; Alibardi, Lorenzo; Falini, Giuseppe; Fermani, Simona; Gazzano, Massimo

2009-12-01

The shed epidermis (molt) of snakes comprises four distinct layers. The upper two layers, here considered as beta-layer, contain essentially beta-keratin. The following layer, known as mesos-layer, is similar to the human stratum corneum, and is formed by thin cells surrounded by intercellular lipids. The latter layer mainly contains alpha-keratin. In this study, the molecular assemblies of proteins and lipids contained in these layers have been analyzed in the scale of two species of snakes, the elapid Tiger snake (TS, Notechis scutatus) and the viperid Gabon viper (GV, Bitis gabonica). Scanning X-ray micro-diffraction, FTIR and Raman spectroscopies, thermal analysis, and scanning electron microscopy experiments confirm the presence of the three layers in the GV skin scale. Conversely, in the TS molt a typical alpha-keratin layer appears to be absent. In the latter, experimental data suggest the presence of two domains similar to those found in the lipid intercellular matrix of stratum corneum. X-ray diffraction data also allow to determine the relative orientation of keratins and lipids. The keratin fibrils are randomly oriented inside the layers parallel to the surface of scales while the lipids are organized in lamellar structures having aliphatic chains normal to the scale surface. The high ordered lipid organization in the mature mesos layer probably increases its effectiveness in limiting water-loss.

Variation of Skin Surface pH, Sebum Content and Stratum Corneum Hydration with Age and Gender in a Large Chinese Population

PubMed Central

Man, M.Q.; Xin, S.J.; Song, S.P.; Cho, S.Y.; Zhang, X.J.; Tu, C.X.; Feingold, K.R.; Elias, P.M.

2009-01-01

Background and Objectives Evidence suggests the importance of skin biophysical properties in predicting diseases and in developing appropriate skin care. The results to date of studies on skin surface pH, stratum corneum (SC) hydration and sebum content in both genders and at various ages have been inconclusive, which was in part due to small sample size. Additionally, little is known about the skin physical properties of Asian, especially Chinese, subjects. In the present study, we assess the difference in skin surface pH, sebum content and SC hydration at various ages and in both genders in a large Chinese population without skin diseases. Methods 713 subjects (328 males and 385 females) aged 0.5–94 years were enrolled in this study. The subjects were divided by age into 5 groups, i.e., 0–12, 13–35, 36–50, 51–70 and over 70 years old. A multifunctional skin physiology monitor was used to measure SC hydration, skin surface pH and sebum content on both the forehead and the forearms. Results In males, the highest sebum content was found on the forearm and the forehead in the age groups 36–50 (93.47 ± 10.01 μg/cm2) and 51–70 years (9.16 ± 1.95 μg/cm2), while in females, the highest sebum content was found on the forearm and the forehead in the age groups 13–35 (61.91 ± 6.12 μg/cm2) and 51–70 years (7.54 ± 2.55 μg/cm2). The forehead sebum content was higher in males aged 13–70 years than in age-matched females; the sebum content on the forehead in both males and females was higher than that on the forearm. Skin surface pH on the forehead of both males and females over the age of 70 years was higher than that in younger groups. SC hydration on the forehead in both males and females was lower above the age of 70, and the one in males aged 13–35 was higher than that in females (43.99 ± 1.88 vs. 36.38 ± 1.67 AU, p < 0.01). SC hydration on the forehead in both males and females did not significantly differ from that on the forearm

Effects of adenosine 5'-monophosphate on epidermal turnover.

PubMed

Furukawa, Fukumi; Kanehara, Shoko; Harano, Fumiki; Shinohara, Shigeo; Kamimura, Junko; Kawabata, Shigekatsu; Igarashi, Sachiyo; Kawamura, Mitsuaki; Yamamoto, Yuki; Miyachi, Yoshiki

2008-10-01

The structure and function of the epidermis is maintained by cell renewal based on epidermal turnover. Epidermal turnover is delayed by aging, and it is thought that the delay of the epidermal turnover is a cause of aging alternation of skin. The epidermal turnover is related to the energy metabolism of epidermal basal cells. Adenosine 5'-triphosphate (ATP) is needed for cell renewal: cell division, and adenosine 5'-monophosphate (AMP) increases the amount of intracellular ATP. These findings suggest that AMP accelerates the epidermal turnover delayed by aging. This study investigated whether AMP and adenosine 5'-monophosphate disodium salt (AMP2Na) accelerates the epidermal turnover. An effect of AMP2Na on cell proliferation was examined by our counting of keratinocytes. An effect of AMP2Na on cell cycle was examined by our counting of basal cells in DNA synthetic period of hairless rats. The effects of AMP2Na (or AMP) on the epidermal turnover were examined by our measuring stratum corneum transit time by use of guinea pigs, and by our measuring stratum corneum surface area by use of hairless rats and in a clinical pharmacological study. The AMP2Na showed two different profiles on the proliferation of primary cultured keratinocytes. At a low concentration it induced cell growth, whereas at a high concentration it inhibited cell growth. The number of basal cells in the DNA synthetic period of AMP2Na was significantly higher than that of the vehicle in hairless rats. The stratum corneum transit time of AMP2Na was significantly shorter than that of the vehicle in guinea pigs. The corneocyte surface area of emulsion containing AMP2Na was significantly smaller than that of the vehicle in volunteers. We conclude that AMP promotes the cell proliferation and the cell cycle progression of epidermal basal cells and accelerates epidermal turnover safely. In addition, AMP is useful for skin rejuvenation in dermatology and aesthetic dermatology.

Anti-cancer vaccination by transdermal delivery of antigen peptide-loaded nanogels via iontophoresis.

PubMed

Toyoda, Mao; Hama, Susumu; Ikeda, Yutaka; Nagasaki, Yukio; Kogure, Kentaro

2015-04-10

Transdermal vaccination with cancer antigens is expected to become a useful anti-cancer therapy. However, it is difficult to accumulate enough antigen in the epidermis for effective exposure to Langerhans cells because of diffusion into the skin and muscle. Carriers, such as liposomes and nanoparticles, may be useful for the prevention of antigen diffusion. Iontophoresis, via application of a small electric current, is a noninvasive and efficient technology for transdermal drug delivery. Previously, we succeeded in the iontophoretic transdermal delivery of liposomes encapsulating insulin, and accumulation of polymer-based nanoparticle nanogels in the stratum corneum of the skin. Therefore, in the present study, we examined the use of iontophoresis with cancer antigen gp-100 peptide KVPRNQDWL-loaded nanogels for anti-cancer vaccination. Iontophoresis resulted in the accumulation of gp-100 peptide and nanogels in the epidermis, and subsequent increase in the number of Langerhans cells in the epidermis. Moreover, tumor growth was significantly suppressed by iontophoresis of the antigen peptide-loaded nanogels. Thus, iontophoresis of the antigen peptide-loaded nanogels may serve as an effective transdermal delivery system for anti-cancer vaccination. Copyright © 2015 Elsevier B.V. All rights reserved.

Correlation of the penetration enhancement with the influence of an alcohol/tocopheryl polyethylene glycol succinate (TPGS) cosolvent system on the molecular structure of the stratum corneum of nude mouse skin as examined by microscopic FTIR/DSC

NASA Astrophysics Data System (ADS)

Liou, Yi-Bo; Ho, Hsiu-O.; Chen, Shin-Yi; Sheu, Ming-Thau

2009-10-01

Tocopheryl polyethylene glycol succinate (TPGS) is a water-soluble derivative of natural source of vitamin E, which possesses a dual nature of lipophilicity and hydrophilicity, similar to a surface-active agent. The penetration enhancement of estradiol by an ethanol and TPGS cosolvent system (EtOH/TPGS) has been confirmed. In this study, the correlation of the penetration enhancement with the influence of the EtOH/TPGS cosolvent system on biophysical changes of the stratum corneum (SC) as examined by Fourier transformation infrared spectrometry differential scanning calorimetry (FTIR/DSC) was investigated. Thermotropic changes in the asymmetrical and symmetrical C-H stretching of hydrocarbon chains of lipids, and amide I and II bands that characterize the protein structure of the SC treated with different concentrations of the EtOH/TPGS cosolvent were examined in this investigation. Results demonstrated that a strong correlation of the influence on biophysical changes of the SC treated with the EtOH/TPGS cosolvent system with the penetration enhancement of estradiol by the corresponding cosolvent system was not evident. It was concluded that the incorporation of TPGS in the cosolvent system seemed only to have insignificantly modified the structural features of the SC. It was not obvious that the penetrant had encountered these modifications resulting in an improvement in the penetration of estradiol by TPGS.

Impact of the long chain omega-acylceramides on the stratum corneum lipid nanostructure. Part 1: Thermotropic phase behaviour of CER[EOS] and CER[EOP] studied using X-ray powder diffraction and FT-Raman spectroscopy.

PubMed

Kessner, Doreen; Brezesinski, Gerald; Funari, Sergio S; Dobner, Bodo; Neubert, Reinhard H H

2010-01-01

The stratum corneum (SC), the outermost layer of the mammalian skin, is the main skin barrier. Ceramides (CERs) as the major constituent of the SC lipid matrix are of particular interest. At the moment, 11 classes of CERs are identified, but the effect of each single ceramide species is still not known. Therefore in this article, the thermotropic behaviour of the long chain omega-acylceramides CER[EOS] and CER[EOP] was studied using X-ray powder diffraction and FT-Raman spectroscopy. It was found that the omega-acylceramides CER[EOS] and CER[EOP] do not show a pronounced polymorphism which is observed for shorter chain ceramides as a significant feature. The phase behaviour of both ceramides is strongly influenced by the extremely long acyl-chain residue. The latter has a much stronger influence compared with the structure of the polar head group, which is discussed as extremely important for the appearance of a rich polymorphism. Despite the strong influence of the long chain, the additional OH-group of the phyto-sphingosine type CER[EOP] influences the lamellar repeat distance and the chain packing. The less polar sphingosine type CER[EOS] is stronger influenced by the long acyl-chain residue. Hydration is necessary for the formation of an extended hydrogen-bonding network between the polar head groups leading to the appearance of a long-periodicity phase (LPP). In contrast, the more polar CER[EOP] forms the LPP with densely packed alkyl chains already in the dry state.

A homozygous nonsense mutation in the gene for Tmem79, a component for the lamellar granule secretory system, produces spontaneous eczema in an experimental model of atopic dermatitis.

PubMed

Sasaki, Takashi; Shiohama, Aiko; Kubo, Akiharu; Kawasaki, Hiroshi; Ishida-Yamamoto, Akemi; Yamada, Taketo; Hachiya, Takayuki; Shimizu, Atsushi; Okano, Hideyuki; Kudoh, Jun; Amagai, Masayuki

2013-11-01

Flaky tail (ma/ma Flg(ft/ft)) mice have a frameshift mutation in the filaggrin (Flg(ft)) gene and are widely used as a model of human atopic dermatitis associated with FLG mutations. These mice possess another recessive hair mutation, matted (ma), and develop spontaneous dermatitis under specific pathogen-free conditions, whereas genetically engineered Flg(-/-) mice do not. We identified and characterized the gene responsible for the matted hair and dermatitis phenotype in flaky tail mice. We narrowed down the responsible region by backcrossing ma/ma mice with wild-type mice and identified the mutation using next-generation DNA sequencing. We attempted to rescue the matted phenotype by introducing the wild-type matted transgene. We characterized the responsible gene product by using whole-mount immunostaining of epidermal sheets. We demonstrated that ma, but not Flg(ft), was responsible for the dermatitis phenotype and corresponded to a Tmem79 gene nonsense mutation (c.840C>G, p.Y280*), which encoded a 5-transmembrane protein. Exogenous Tmem79 expression rescued the matted hair and dermatitis phenotype of Tmem79(ma/ma) mice. Tmem79 was mainly expressed in the trans-Golgi network in stratum granulosum cells in the epidermis in both mice and humans. The Tmem79(ma/ma) mutation impaired the lamellar granule secretory system, which resulted in altered stratum corneum formation and a subsequent spontaneous dermatitis phenotype. The Tmem79(ma/ma) mutation is responsible for the spontaneous dermatitis phenotype in matted mice, probably as a result of impaired lamellar granule secretory system and altered stratum corneum barrier function. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Matriptase initiates epidermal prokallikrein activation and disease onset in a mouse model of Netherton syndrome

PubMed Central

Sales, Katiuchia Uzzun; Masedunskas, Andrius; Bey, Alexandra L.; Rasmussen, Amber; Weigert, Roberto; List, Karin; Szabo, Roman; Overbeek, Paul A.; Bugge, Thomas H.

2010-01-01

Deficiency in the serine protease inhibitor LEKTI is the etiological origin of Netherton syndrome. The principal morbidities of the disease are stratum corneum detachment and chronic inflammation. We show that the membrane protease, matriptase, initiates Netherton syndrome in a LEKTI-deficient mouse model by premature activation of a pro-kallikrein-related cascade. Auto-activation of pro-inflammatory and stratum corneum detachment-associated pro-kallikrein-related peptidases was either low or undetectable, but they were efficiently activated by matriptase. Ablation of matriptase from LEKTI-deficient mice dampened inflammation, eliminated aberrant protease activity, prevented stratum corneum detachment, and improved epidermal barrier function. The study uncovers a pathogenic matriptase-pro-kallikrein pathway that could be operative in several human skin and inflammatory diseases. PMID:20657595

Skin hydration and lifestyle-related factors in community-dwelling older people.

PubMed

Iizaka, Shinji

2017-09-01

This study aimed to investigate skin hydration status of the lower legs by comparing several methods and examining lifestyle-related factors in community-dwelling older people. A cross-sectional study was conducted in three community settings in Japan from autumn to winter. Participants were older people aged ≥65 years (n=118). Skin hydration status of the lower legs was evaluated by stratum corneum hydration using an electrical device, clinical symptoms by an expert's observation and the visual analogue scale. Lifestyle factors of skin care were evaluated by a self-administered questionnaire. The mean age of participants was 74.4 years and 83.9% were women. Stratum corneum hydration was significantly correlated with clinical scores by an expert's observation (rho=-0.46, P<0.001), but it was not correlated with the visual analogue scale (rho=-0.08, P=0.435). Among participants who did not perceive dry skin, 57.5% showed low stratum corneum hydration. Hospitalization in the past year (b=-9.4, P=0.008), excessive bathing habits (b=-4.6, P=0.014), and having an outdoor hobby (b=-5.7, P=0.007) were negatively associated, and diuretics (b=11.5, P=0.002) and lotion-type moisturizer use (b=4.6, P=0.022) were positively associated with stratum corneum hydration. Stratum corneum hydration measurements show an adequate association with observation-based evaluation by an expert, but poor agreement with subjective evaluation in community-dwelling older people. Hospitalization experience and lifestyle factors are associated with skin hydration. Copyright © 2017 Elsevier B.V. All rights reserved.

Skin penetration and kinetics of pristine fullerenes (C{sub 60}) topically exposed in industrial organic solvents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xia, Xin R., E-mail: xia@ncsu.ed; Monteiro-Riviere, Nancy A.; Riviere, Jim E.

2010-01-01

Pristine fullerenes (C{sub 60}) in different solvents will be used in many industrial and pharmaceutical manufacturing and derivatizing processes. This report explores the impact of solvents on skin penetration of C{sub 60} from different types of industrial solvents (toluene, cyclohexane, chloroform and mineral oil). Yorkshire weanling pigs (n = 3) were topically dosed with 500 muL of 200 mug/mL C{sub 60} in a given solvent for 24 h and re-dosed daily for 4 days to simulate the worst scenario in occupational exposures. The dose sites were tape-stripped and skin biopsies were taken after 26 tape-strips for quantitative analysis. When dosedmore » in toluene, cyclohexane or chloroform, pristine fullerenes penetrated deeply into the stratum corneum, the primary barrier of skin. More C{sub 60} was detected in the stratum corneum when dosed in chloroform compared to toluene or cyclohexane. Fullerenes were not detected in the skin when dosed in mineral oil. This is the first direct evidence of solvent effects on the skin penetration of pristine fullerenes. The penetration of C{sub 60} into the stratum corneum was verified using isolated stratum corneum in vitro; the solvent effects on the stratum corneum absorption of C{sub 60} were consistent with those observed in vivo. In vitro flow-through diffusion cell experiments were conducted in pig skin and fullerenes were not detected in the receptor solutions by 24 h. The limit of detection was 0.001 mug/mL of fullerenes in 2 mL of the receptor solutions.« less

Sample allocation balancing overall representativeness and stratum precision.

PubMed

Diaz-Quijano, Fredi Alexander

2018-05-07

In large-scale surveys, it is often necessary to distribute a preset sample size among a number of strata. Researchers must make a decision between prioritizing overall representativeness or precision of stratum estimates. Hence, I evaluated different sample allocation strategies based on stratum size. The strategies evaluated herein included allocation proportional to stratum population; equal sample for all strata; and proportional to the natural logarithm, cubic root, and square root of the stratum population. This study considered the fact that, from a preset sample size, the dispersion index of stratum sampling fractions is correlated with the population estimator error and the dispersion index of stratum-specific sampling errors would measure the inequality in precision distribution. Identification of a balanced and efficient strategy was based on comparing those both dispersion indices. Balance and efficiency of the strategies changed depending on overall sample size. As the sample to be distributed increased, the most efficient allocation strategies were equal sample for each stratum; proportional to the logarithm, to the cubic root, to square root; and that proportional to the stratum population, respectively. Depending on sample size, each of the strategies evaluated could be considered in optimizing the sample to keep both overall representativeness and stratum-specific precision. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of skin barrier disruption on immune responses to topically applied cross-reacting material, CRM(197), of diphtheria toxin.

PubMed

Godefroy, S; Peyre, M; Garcia, N; Muller, S; Sesardic, D; Partidos, C D

2005-08-01

The high accessibility of the skin and the presence of immunocompetent cells in the epidermis makes this surface an attractive route for needle-free administration of vaccines. However, the lining of the skin by the stratum corneum is a major obstacle to vaccine delivery. In this study we examined the effect of skin barrier disruption on the immune responses to the cross-reacting material CRM(197), a nontoxic mutant of diphtheria toxin (DTx) that is considered as a vaccine candidate. Application of CRM(197), together with cholera toxin (CT), onto the tape-stripped skin of mice elicited antibody responses that had anti-DTx neutralizing activity. Vaccine delivery onto mildly ablated skin or intact skin did not elicit any detectable anti-CRM(197) antibodies. Mice immunized with CRM(197) alone onto the tape-stripped skin mounted a vigorous antigen-specific proliferative response. In contrast, the induction of cellular immunity after CRM(197) deposition onto mildly ablated or intact skin was adjuvant dependent. Furthermore, epidermal cells were activated and underwent apoptosis that was more pronounced when the stratum corneum was removed by tape stripping. Overall, these findings highlight the potential for transcutaneous delivery of CRM(197) and establish a correlation between the degree of barrier disruption and levels of antigen-specific immune responses. Moreover, these results provide the first evidence that the development of a transcutaneous immunization strategy for diphtheria, based on simple and practical methods to disrupt the skin barrier, is feasible.

Determination of the effect of lipophilicity on the in vitro permeability and tissue reservoir characteristics of topically applied solutes in human skin layers.

PubMed

Cross, Sheree E; Magnusson, Beatrice M; Winckle, Gareth; Anissimov, Yuri; Roberts, Michael S

2003-05-01

In order to establish the relationship between solute lipophilicity and skin penetration (including flux and concentration behavior), we examined the in vitro penetration and membrane concentration of a series of homologous alcohols (C2-C10) applied topically in aqueous solutions to human epidermal, full-thickness, and dermal membranes. The partitioning/distribution of each alcohol between the donor solution, stratum corneum, viable epidermis, dermis, and receptor phase compartments was determined during the penetration process and separately to isolated samples of each tissue type. Maximum flux and permeability coefficients are compared for each membrane and estimates of alcohol diffusivity are made based on flux/concentration data and also the related tissue resistance (the reciprocal of permeability coefficient) for each membrane type. The permeability coefficient increased with increasing lipophilicity to alcohol C8 (octanol) with no further increase for C10 (decanol). Log vehicle:stratum corneum partition coefficients were related to logP, and the concentration of alcohols in each of the tissue layers appeared to increase with lipophilicity. No difference was measured in the diffusivity of smaller more polar alcohols in the three membranes; however, the larger more lipophilic solutes showed slower diffusivity values. The study showed that the dermis may be a much more lipophilic environment than originally believed and that distribution of smaller nonionized solutes into local tissues below a site of topical application may be estimated based on knowledge of their lipophilicity alone.

Confocal laser scanning microscopy to estimate nanoparticles' human skin penetration in vitro.

PubMed

Zou, Ying; Celli, Anna; Zhu, Hanjiang; Elmahdy, Akram; Cao, Yachao; Hui, Xiaoying; Maibach, Howard

2017-01-01

With rapid development of nanotechnology, there is increasing interest in nanoparticle (NP) application and its safety and efficacy on human skin. In this study, we utilized confocal laser scanning microscopy to estimate NP skin penetration. Three different-sized polystyrene NPs marked with red fluorescence were applied to human skin, and Calcium Green 5N was used as a counterstain. Dimethyl sulfoxide (DMSO) and ethanol were used as alternative vehicles for NPs. Tape stripping was utilized as a barrier-damaged skin model. Skin biopsies dosed with NPs were incubated at 4°C or 37°C for 24 hours and imaged using confocal laser scanning microscopy. NPs were localized in the stratum corneum (SC) and hair follicles without penetrating the epidermis/dermis. Barrier alteration with tape stripping and change in incubation temperature did not induce deeper penetration. DMSO enhanced NP SC penetration but ethanol did not. Except with DMSO vehicle, these hydrolyzed polystyrene NPs did not penetrate intact or barrier-damaged human "viable" epidermis. For further clinical relevance, in vivo human skin studies and more sensitive analytic chemical methodology are suggested.

Distribution of keratin and associated proteins in the epidermis of monotreme, marsupial, and placental mammals.

PubMed

Alibardi, Lorenzo; Maderson, Paul F A

2003-10-01

, eutherian-derived anti-loricrin antibodies show a weak to intense cross-reactivity to KHGs and corneous tissues of both orthokeratotic and parakeratotic epidermis in monotremes and marsupials. High-resolution immunogold analysis of loricrin distribution in immature keratinocytes of platypus parakeratotic web epidermis identifies labeled areas of round or irregular, electron-pale granules within the denser keratohyalin component and keratin network. In the deepest mature tissues, loricrin-like labeling is diffuse throughout the cytoplasm, so that cells lack the preferential distribution of loricrin along the corneous envelope that characterizes mature eutherian keratinocytes. Thus, the irregular distribution of loricrin in platypus parakeratotic tissues more resembles that which has been described for reptilian and avian keratinocytes. These observations on the noneutherian epidermis show that a stratum granulosum is present to different degrees, even discontinuous within one tissue, so that parakeratotic and orthokeratotic areas may alternate: this might imply that parakeratotic monotreme epidermis reflects the primitive pattern of amniote alpha-keratogenesis. Absent from anamniote epidermis and all sauropsid beta-keratogenic tissues, the ubiquitous presence of a loricrin-like protein as a major component of other amniote corneous tissues suggests that this is a primitive feature of amniote alpha-keratogenesis. The apparent lack of specific regionalization of loricin near the plasma membranes of monotreme keratinocytes could be an artifactual result of the immunofluorescence technique employed, or there may be masking of the antigenicity of loricrin-like proteins once they are incorporated into the corneous envelope. Nevertheless, the mechanism of redistribution of such proteins during maturation of monotreme keratinocytes is different from, perhaps more primitive, or less specialized, than that in the epidermis of eutherian mammals. Copyright 2003 Wiley-Liss, Inc.

Gravimetric method for in vitro calibration of skin hydration measurements.

PubMed

Martinsen, Ørjan G; Grimnes, Sverre; Nilsen, Jon K; Tronstad, Christian; Jang, Wooyoung; Kim, Hongsig; Shin, Kunsoo; Naderi, Majid; Thielmann, Frank

2008-02-01

A novel method for in vitro calibration of skin hydration measurements is presented. The method combines gravimetric and electrical measurements and reveals an exponential dependency of measured electrical susceptance to absolute water content in the epidermal stratum corneum. The results also show that absorption of water into the stratum corneum exhibits three different phases with significant differences in absorption time constant. These phases probably correspond to bound, loosely bound, and bulk water.

Water-filtered infrared-A (wIRA) can act as a penetration enhancer for topically applied substances

PubMed Central

Otberg, Nina; Grone, Diego; Meyer, Lars; Schanzer, Sabine; Hoffmann, Gerd; Ackermann, Hanns; Sterry, Wolfram; Lademann, Jürgen

2008-01-01

Background: Water-filtered infrared-A (wIRA) irradiation has been shown to enhance penetration of clinically used topically applied substances in humans through investigation of functional effects of penetrated substances like vasoconstriction by cortisone. Aim of the study: Investigation of the influence of wIRA irradiation on the dermatopharmacokinetics of topically applied substances by use of optical methods, especially to localize penetrating substances, in a prospective randomised controlled study in humans. Methods: The penetration profiles of the hydrophilic dye fluorescein and the lipophilic dye curcumin in separate standard water-in-oil emulsions were determined on the inner forearm of test persons by tape stripping in combination with spectroscopic measurements. Additionally, the penetration was investigated in vivo by laser scanning microscopy. Transepidermal water loss, hydration of the epidermis, and surface temperature were determined. Three different procedures (modes A, B, C) were used in a randomised order on three separate days of investigation in each of 12 test persons. In mode A, the two dyes were applied on different skin areas without water-filtered infrared-A (wIRA) irradiation. In mode B, the skin surface was irradiated with wIRA over 30 min before application of the two dyes (Hydrosun® radiator type 501, 10 mm water cuvette, orange filter OG590, water-filtered spectrum: 590–1400 nm with dominant amount of wIRA). In mode C, the two dyes were applied and immediately afterwards the skin was irradiated with wIRA over 30 min. In all modes, tape stripping started 30 min after application of the formulations. Main variable of interest was the ratio of the amount of the dye in the deeper (second) 10% of the stratum corneum to the amount of the dye in the upper 10% of the stratum corneum. Results: The penetration profiles of the hydrophilic fluorescein showed in case of pretreatment or treatment with wIRA (modes B and C) an increased

Current and future technological advances in transdermal gene delivery.

PubMed

Chen, Xianfeng

2017-12-19

Transdermal gene delivery holds significant advantages as it is able to minimize the problems of systemic administration such as enzymatic degradation, systemic toxicity, and poor delivery to target tissues. This technology has the potential to transform the treatment and prevention of a range of diseases. However, the skin poses a great barrier for gene delivery because of the "bricks-and-mortar" structure of the stratum corneum and the tight junctions between keratinocytes in the epidermis. This review systematically summarizes the typical physical and chemical approaches to overcome these barriers and facilitate gene delivery via skin for applications in vaccination, wound healing, skin cancers and skin diseases. Next, the advantages and disadvantages of different approaches are discussed and the insights for future development are provided. Copyright © 2017 Elsevier B.V. All rights reserved.

Black-spot poison ivy dermatitis. An acute irritant contact dermatitis superimposed upon an allergic contact dermatitis.

PubMed

Hurwitz, R M; Rivera, H P; Guin, J D

1984-08-01

A black spot in the epidermis over a blister of poison ivy dermatitis is an uncommon finding. Four patients with the phenomenon are described. Histologic and histochemical studies were made on biopsy material and the blackish deposit on the skin surface was compared with black deposits in and on leaves of the species of poison ivy. This examination revealed a yellow, amorphous substance on the stratum corneum of the lesions and a similar substance in and on leaves of the poison ivy plant, Toxicodendron radicans ssp. negundo. Associated with the pigmentary deposits there were distinct changes of acute irritant contact dermatitis superimposed upon allergic contact dermatitis. Our findings support the view that the black material is the oleoresin of the plant, and that this substance behaves both as an irritant and an allergen.

Dexpanthenol enhances skin barrier repair and reduces inflammation after sodium lauryl sulphate-induced irritation.

PubMed

Proksch, E; Nissen, H P

2002-12-01

Dexpanthenol-containing creams have been widely used for treatment of lesions (superficial wounds) of the skin and mucous membranes. Dexpanthenol is converted in tissues to pantothenic acid, a component of coenzyme A. Coenzyme A catalyses early steps in the synthesis of fatty acids and sphingolipids which are of crucial importance for stratum corneum lipid bilayers and cell membrane integrity. In the present study, the effects were examined of a dexpanthenol-containing cream on skin barrier repair, stratum corneum hydration, skin roughness, and inflammation after sodium lauryl sulphate (SLS)-induced irritation. Irritation was induced by application of SLS in patch test chambers. The dexpanthenol-contaming cream or the vehicle were applied twice daily and barrier repair, hydration, roughness, and inflammation of the skin were determined by using biophysical methods. Significantly accelerated skin barrier repair was found in treatments with the dexpanthenol-containing cream (verum) compared with vehicle-treated (placebo) or untreated skin. Both verum and placebo showed an increase in stratum corneum hydration, but significantly more so with the dexpanthenol-containing cream. Both creams reduced skin roughness, but again the verum was superior. The dexpanthenol-containing cream significantly reduced skin redness as a sign of inflammation in contrast to the vehicle, which produced no effect. Treatment with a dexpanthenol-containing cream showed significantly enhanced skin barrier repair and stratum corneum hydration, while reducing skin roughness and inflammation.

Status of surfactants as penetration enhancers in transdermal drug delivery

PubMed Central

Som, Iti; Bhatia, Kashish; Yasir, Mohd.

2012-01-01

Surfactants are found in many existing therapeutic, cosmetic, and agro-chemical preparations. In recent years, surfactants have been employed to enhance the permeation rates of several drugs via transdermal route. The application of transdermal route to a wider range of drugs is limited due to significant barrier to penetration across the skin which is associated with the outermost stratum corneum layer. Surfactants have effects on the permeability characteristics of several biological membranes including skin. They have the potential to solubilize lipids within the stratum corneum. The penetration of the surfactant molecule into the lipid lamellae of the stratum corneum is strongly dependent on the partitioning behavior and solubility of surfactant. Surfactants ranging from hydrophobic agents such as oleic acid to hydrophilic sodium lauryl sulfate have been tested as permeation enhancer to improve drug delivery. This article reviews the status of surfactants as permeation enhancer in transdermal drug delivery of various drugs. PMID:22368393

Detecting electroporation by assessing the time constants in the exponential response of human skin to voltage controlled impulse electrical stimulation.

PubMed

Bîrlea, Sinziana I; Corley, Gavin J; Bîrlea, Nicolae M; Breen, Paul P; Quondamatteo, Fabio; OLaighin, Gearóid

2009-01-01

We propose a new method for extracting the electrical properties of human skin based on the time constant analysis of its exponential response to impulse stimulation. As a result of this analysis an adjacent finding has arisen. We have found that stratum corneum electroporation can be detected using this analysis method. We have observed that a one time-constant model is appropriate for describing the electrical properties of human skin at low amplitude applied voltages (<30V), and a two time-constant model best describes skin electrical properties at higher amplitude applied voltages (>30V). Higher voltage amplitudes (>30V) have been proven to create pores in the skin's stratum corneum which offer a new, lower resistance, pathway for the passage of current through the skin. Our data shows that when pores are formed in the stratum corneum they can be detected, in-vivo, due to the fact that a second time constant describes current flow through them.

Assessment of dermatopharmacokinetic approach in the bioequivalence determination of topical tretinoin gel products.

PubMed

Pershing, Lynn K; Nelson, Joel L; Corlett, Judy L; Shrivastava, Surendra P; Hare, Don B; Shah, Vinod P

2003-05-01

A new dermatopharmacokinetic (DPK) approach has been proposed for bioequivalence determination of topical drug products by comparing the drug content kinetics in stratum corneum. We sought to establish any correlation between clinical safety/efficacy and DPK approach in bioequivalence determination of tretinoin gel 0.025%. Tretinoin and isotretinoin were quantified in human volar forearm stratum corneum as a function of time with 3 tretinoin gel 0.025% products in 49 patients. Stratum corneum layers were harvested using multiple adhesive disks, which were subsequently extracted and quantified for both isomers by high-performance liquid chromatography. Products with similar composition and therapeutic equivalence were found bioequivalent, and products with different composition and clinical profiles were found bioinequivalent by DPK methodology. There is a direct correlation between DPK parameters in healthy patients and clinical safety/efficacy of tretinoin gel products in patients with acne. Data support the use of DPK parameters and methodology in the bioequivalence assessment of topical tretinoin gel products.

A topical treatment containing heat-treated Lactobacillus johnsonii NCC 533 reduces Staphylococcus aureus adhesion and induces antimicrobial peptide expression in an in vitro reconstructed human epidermis model.

PubMed

Rosignoli, Carine; Thibaut de Ménonville, Séverine; Orfila, Danielle; Béal, Méline; Bertino, Béatrice; Aubert, Jérôme; Mercenier, Annick; Piwnica, David

2018-04-01

Staphylococcus aureus colonization is thought to contribute to the pathophysiology of atopic dermatitis (AD). AD patients exhibit reduced levels of cutaneous antimicrobial peptides (AMPs), which may explain their increased susceptibility to infections. Using an in vitro reconstructed human epidermis (RHE) model, we sought to determine whether topical application of a non-replicating probiotic, heat-treated Lactobacillus johnsonii NCC 533 (HT La1), could inhibit S. aureus adhesion to skin and boost cutaneous innate immunity. We found that application of HT La1 suspension to RHE samples reduced the binding of radiolabelled S. aureus by up to 74%. To investigate a potential effect of HT La1 on innate immunity, we analysed the expression of nine AMP genes, including those encoding beta defensins and S100 proteins, following topical application of HT La1 in suspension or in a daily moisturizer lotion. Analysed genes were induced by up to fourfold in a dose-dependent manner by HT La1 in suspension and by up to 2.4-fold by HT La1 in the moisturizer lotion. Finally, using ELISA and immunohistochemical detection, we evaluated the expression and secretion of the AMPs hBD-2 and psoriasin and determined that both proteins were induced by topical HT La1, particularly in the stratum corneum of the RHE. These findings demonstrate that a topically applied, non-replicating probiotic can modulate endogenous AMP expression and inhibit binding of S. aureus to an RHE model in vitro. Moreover, they suggest that a topical formulation containing HT La1 could benefit atopic skin by enhancing cutaneous innate immunity and reducing S. aureus colonization. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Quantification of changes in skin hydration and sebum after tape stripping using infrared spectroscopy

NASA Astrophysics Data System (ADS)

Ezerskaia, A.; Pereira, S. F.; Urbach, H. P.; Varghese, B.

2017-02-01

Skin barrier function relies on well balanced water and lipid system of stratum corneum. Optimal hydration and oiliness levels are indicators of skin health and integrity. We demonstrate an accurate and sensitive depth profiling of stratum corneum sebum and hydration levels using short wave infrared spectroscopy in the spectral range around 1720 nm. We demonstrate that short wave infrared spectroscopic technique combined with tape stripping can provide morequantitative and more reliable skin barrier function information in the low hydration regime, compared to conventional biophysical methods.

Electrical Stimulation for Wound-Healing: Simulation on the Effect of Electrode Configurations

PubMed Central

2017-01-01

Endogenous electric field is known to play important roles in the wound-healing process, mainly through its effects on protein synthesis and cell migration. Many clinical studies have demonstrated that electrical stimulation (ES) with steady direct currents is beneficial to accelerating wound-healing, even though the underlying mechanisms remain unclear. In the present study, a three-dimensional finite element wound model was built to optimize the electrode configuration in ES. Four layers of the skin, stratum corneum, epidermis, dermis, and subcutis, with defined thickness and electrical properties were modeled. The main goal was to evaluate the distributions of exogenous electric fields delivered with direct current (DC) stimulation using different electrode configurations such as sizes and positions. Based on the results, some guidelines were obtained in designing the electrode configuration for applications of clinical ES. PMID:28497054

Kinetics of the maintenance of the epidermis

NASA Astrophysics Data System (ADS)

Zhdanov, Vladimir P.; Cho, Nam-Joon

2013-08-01

The epidermis is the outermost layer of skin. It is comprised of keratin-containing cells called keratinocytes. Functionally, the epidermis serves as a physical barrier that can prevent infection and regulate body hydration. Maintenance and repair of the epidermis are important for human health. Mechanistically, these processes occur primarily via proliferation and differentiation of stem cells located in the basal monolayer. These processes are believed to depend on cell-cell communication and spatial constraints but existing kinetic models focus mainly on proliferation and differentiation. To address this issue, we present a mean-field kinetic model that takes these additional factors into account and describes the epidermis at a biosystem level. The corresponding equations operate with the populations of stem cells and differentiated cells in the basal layer. The keratinocytes located above the basal layer are treated at a more coarse-grained level by considering the thickness of the epidermis. The model clarifies the likely role of various negative feedbacks that may control the epidermis and, accordingly, provides insight into the cellular mechanisms underlying complex biological phenomena such as wound healing.

Technical parameters of vertical in vivo multiphoton microscopy: a critical evaluation of the flyscanning method

NASA Astrophysics Data System (ADS)

Czekalla, C.; Schönborn, K. H.; Markworth, S.; Ulrich, M.; Göppner, D.; Gollnick, H.; Röwert-Huber, J.; Darvin, M. E.; Lademann, J.; Meinke, M. C.

2015-08-01

The optical biopsy could be a quick and painless support or alternative to a punch biopsy. In this letter the first in vivo vertical wide field two photon microscopy (2PM) images of healthy volunteers are shown. The 2PM images are fused images of two photon excited auto fluorescence (AF) and second harmonic generation (SHG) signals given as false-color images of 200 μm  ×  7 mm in size. By using these two nonlinear effects, the epidermis can be easily distinguished from the dermis at a glance. The auto fluorescence provides cellular resolution of the epidermal cells, and elastin fibers are partly visible in the dermis. Collagen, visible by SHG signal, is the dominant structure in the dermis. As contact agent water was evaluated to increase the AF signal, especially in the deeper layers of epidermis and dermis. For further improvement any terminal hairs should be removed by shaving and by taking tape strips of the first five layers of the stratum corneum. The first images illustrated that young skin compared to aged skin shows remarkably different dermal elastin and collagen signals in the dermis.

Confocal laser scanning microscopy to estimate nanoparticles’ human skin penetration in vitro

PubMed Central

Elmahdy, Akram; Cao, Yachao; Hui, Xiaoying; Maibach, Howard

2017-01-01

Objective With rapid development of nanotechnology, there is increasing interest in nanoparticle (NP) application and its safety and efficacy on human skin. In this study, we utilized confocal laser scanning microscopy to estimate NP skin penetration. Methods Three different-sized polystyrene NPs marked with red fluorescence were applied to human skin, and Calcium Green 5N was used as a counterstain. Dimethyl sulfoxide (DMSO) and ethanol were used as alternative vehicles for NPs. Tape stripping was utilized as a barrier-damaged skin model. Skin biopsies dosed with NPs were incubated at 4°C or 37°C for 24 hours and imaged using confocal laser scanning microscopy. Results NPs were localized in the stratum corneum (SC) and hair follicles without penetrating the epidermis/dermis. Barrier alteration with tape stripping and change in incubation temperature did not induce deeper penetration. DMSO enhanced NP SC penetration but ethanol did not. Conclusion Except with DMSO vehicle, these hydrolyzed polystyrene NPs did not penetrate intact or barrier-damaged human “viable” epidermis. For further clinical relevance, in vivo human skin studies and more sensitive analytic chemical methodology are suggested. PMID:29184403

Volumetric Visualization of Human Skin

NASA Astrophysics Data System (ADS)

Kawai, Toshiyuki; Kurioka, Yoshihiro

We propose a modeling and rendering technique of human skin, which can provide realistic color, gloss and translucency for various applications in computer graphics. Our method is based on volumetric representation of the structure inside of the skin. Our model consists of the stratum corneum and three layers of pigments. The stratum corneum has also layered structure in which the incident light is reflected, refracted and diffused. Each layer of pigment has carotene, melanin or hemoglobin. The density distributions of pigments which define the color of each layer can be supplied as one of the voxel values. Surface normals of upper-side voxels are fluctuated to produce bumps and lines on the skin. We apply ray tracing approach to this model to obtain the rendered image. Multiple scattering in the stratum corneum, reflective and absorptive spectrum of pigments are considered. We also consider Fresnel term to calculate the specular component for glossy surface of skin. Some examples of rendered images are shown, which can successfully visualize a human skin.

When to suspect tinea; a histopathologic study of 103 cases of PAS-positive tinea.

PubMed

Elbendary, Amira; Valdebran, Manuel; Gad, AbdAllah; Elston, Dirk M

2016-10-01

The histopathologic features of tinea vary widely and its diagnosis could be easily missed if the index of suspicion is not high. We aimed in this study to detect histopathologic features that could be a clue for diagnosis We retrospectively reviewed 103 cases of tinea, confirmed by Periodic acid-Schiff (PAS) staining. For each case, gender, biopsy site, and pre-biopsy suspicion were recorded. The presence or absence of 17 microscopic features was noted. Concordance between pre-biopsy and histopathologic diagnosis was noted in 57.28% of cases, suggesting that the diagnosis is often not suspected clinically. Among the histopathologic features studied, a compact stratum corneum (either uniform or forming a layer beneath a basket weave stratum corneum), parakeratosis, mild spongiosis and neutrophils in the stratum corneum and within the blood vessels were the most frequent features noted. This study suggests histopathologic clues that should prompt the pathologist to order a PAS stain, especially when diagnosis is not suspected clinically. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Topically applied vitamin C and cysteine derivatives protect against UVA-induced photodegradation of suprofen in ex vivo pigskin.

PubMed

Moison, Ralf M W; Rijnkels, Jolanda M; Podda, Elena; Righele, Francesca; Tomasello, Federica; Caffieri, Sergio; Beijersbergen van Henegouwen, Gerard M J

2003-04-01

Exposure of the nonsteroidal anti-inflammatory drug suprofen (SUP) to UV-radiation results in the formation of radicals, reactive oxygen species (ROS), photodecarboxylated products and photoadducts with biomacromolecules. Using an ex vivo pigskin explant model, we investigated whether topical coapplication of the water-soluble antioxidants vitamin C (Lascorbic acid, ASC), N-acetyl-L-cysteine (NAC) or L-cysteine ethylester (CYSET) with SUP reduced ultraviolet A (UVA)-induced decomposition of SUP. UVA-induced changes in antioxidant bioavailability in the stratum corneum and epidermis were also studied. Epidermal bioavailability of SUP in sham-irradiated pigskin increased 2.2- to 4.1-fold after the lowest antioxidant doses (P < 0.05). As compared with no applied antioxidant, increasing doses of all tested antioxidants resulted in increased levels of SUP and decreased levels of photoproducts (P < 0.05). A maximal protection against SUP photodegradation of 70% was found after an ASC dose of 1 micromol/cm2; these values were 60% for a NAC dose of 10 micromol/cm2 and 50% for a CYSET dose of 5 micromol/cm2. Skin antioxidant levels increased with increasing applied dose (P < 0.05); the bioavailability of CYSET was approximately three-fold lower than that of ASC and NAC. UVA exposure resulted in 30-50% consumption of the topically applied ASC or NAC in the stratum corneum, whereas CYSET was not consumed. In conclusion, the topically applied water-soluble antioxidants ASC, NAC and CYSET protect against UVA-induced decomposition of SUP by scavenging radicals and ROS. Coapplication of these antioxidants may therefore be an effective way to reduce or prevent the phototoxic effects of SUP in vivo.

Update of Ablative Fractionated Lasers to Enhance Cutaneous Topical Drug Delivery.

PubMed

Waibel, Jill S; Rudnick, Ashley; Shagalov, Deborah R; Nicolazzo, Danielle M

2017-08-01

Ablative fractional lasers (AFXL) enhance uptake of therapeutics and this newly emerging field is called laser-assisted drug delivery (LAD). This new science has emerged over the past decade and is finding its way into clinical practice. LAD is poised to change how medicine delivers drugs. Topical and systemic application of pharmaceutical agents for therapeutic effect is an integral part of medicine. With topical therapy, the stratum corneum barrier of the skin impairs the ability of drugs to enter the body. The purpose of LAD is to alter the stratum corneum, epidermis, and dermis to facilitate increased penetration of a drug, device, or cell to its respected target. AFXL represents an innovative, non-invasive strategy to overcome the epidermal barrier. LAD employs three steps: (1) breakdown of the skin barrier with a laser, (2) optional use a laser for a therapeutic effect, (3) delivery of the medicine through laser channels to further enhance the therapeutic effect. The advantages of using lasers for drug delivery include the ease of accessibility, the non-invasive aspect, and its effectiveness. By changing the laser settings, one may use LAD to have a drug remain locally within the skin or to have systemic delivery. Many drugs are not intended for use in the dermis and so it has yet to be determined which drugs are appropriate for this technique. It appears this developing technology has the ability to be a new delivery system for both localized and systemic delivery of drugs, cells, and other molecules. With responsible development AFXL-assisted drug delivery may become a new important part of medicine.

Structural Changes in the Skin of Hairless Mice Following Exposure to Sulfur Mustard Correlate with Inflammation and DNA Damage

PubMed Central

Joseph, Laurie B.; Gerecke, Donald R.; Heck, Diane E.; Black, Adrienne T.; Sinko, Patrick J.; Cervelli, Jessica A.; Casillas, Robert P.; Babin, Michael C.; Laskin, Debra L.; Laskin, Jeffrey D.

2011-01-01

Sulfur mustard (SM, bis(2-chloroethyl)sulfide) is a bifunctional alkylating agent that causes dermal inflammation, edema and blistering. To investigate the pathogenesis of SM-induced injury, we used a vapor cup model which provides an occlusive environment in which SM is in constant contact with the skin. The dorsal skin of SKH-1 hairless mice was exposed to saturated SM vapor or air control. Histopathological changes, inflammatory markers and DNA damage were analyzed 1–14 days later. After 1 day, SM caused epidermal thinning, stratum corneum shedding, basal cell karyolysis, hemorrhage and macrophage and neutrophil accumulation in the dermis. Cleaved caspase-3 and phosphorylated histone 2A.X (phospho-H2A.X), markers of apoptosis and DNA damage, respectively, were increased whereas proliferating cell nuclear antigen (PCNA) was down-regulated after SM exposure. By 3 days, epithelial cell hypertrophy, edema, parakeratosis and loss of epidermal structures were noted. Enzymes generating pro-inflammatory mediators including myeloperoxidase and cyclooxygenase-2 were upregulated. After 7 days, keratin-10, a differentiation marker, was evident in the stratum corneum. This was associated with an underlying eschar, as neoepidermis began to migrate at the wound edges. Trichrome staining revealed increased collagen deposition in the dermis. PCNA expression in the epidermis was correlated with hyperplasia, hyperkeratosis, and parakeratosis. By 14 days, there was epidermal regeneration with extensive hyperplasia, and reduced expression of cleaved caspase-3, cyclooxygenase-2 and phospho-H2A.X. These findings are consistent with the pathophysiology of SM-induced skin injury in humans suggesting that the hairless mouse can be used to investigate the dermatoxicity of vesicants and the potential efficacy of countermeasures. PMID:21672537

Relationship between biochemical factors and skin symptoms in chronic venous disease.

PubMed

Takai, Yasushi; Hiramoto, Keiichi; Nishimura, Yoshiyuki; Ooi, Kazuya

2017-05-01

Chronic venous disease (CVD) is a common venous disease of the lower extremities and patients often develop symptoms of itching and skin roughness. An easy to use and objective skin examination was recently developed that allows measurement of the level of stratum corneum content and transepidermal water loss (TEWL), which can indicate the status of the barrier function of the stratum corneum. Previous studies demonstrated that histamine production from mast cells, and tryptase and matrix metalloprotease-9 levels were associated with skin inflammation. This study aimed to clarify the relationship between dry skin and inflammatory mediators that mediate the skin symptoms of CVD subjects. The study enrolled 27 subjects with CVD and a control group consisting of 9 volunteers. The itching onset frequency was higher in women (70.4%) compared with men (50.0%). To analyze the mechanisms involved in itching we measured blood inflammatory mediators pre- and post-sclerotherapy. There was a significant decrease in Substance P, histamine, IgE, and tryptase levels post-sclerotherapy compared with those at pre-sclerotherapy. These levels were associated with the severity of itching. In addition, compared with the control subjects, there was a significant increase in the stratum corneum water content and a decrease in the TEWL in the 27 patients with CVD. This was associated with a decrease in the itching symptoms. Our findings indicate that sclerotherapy decreased levels of inflammatory mediators, increased stratum corneum water content and decreased TEWL, which coincided with reduced itching in CVD patients, indicating they might be therapeutic targets.

Sensory transduction and the mammalian epidermis.

PubMed

Hoath, S B; Donnelly, M M; Boissy, R E

1990-01-01

This paper constitutes, in its main intent, an introduction to the mammalian epidermis as a surface for biosensor applications. In particular, the structure and function of the epidermis of the newborn rat are examined as a model for studies of the human state. Data are presented illustrating an anisotropic organization of the dorsal surface of the neonatal rodent with regard to line of tension and thermal gradients. The dependence of the mechanical properties of the epidermis upon calcium is examined by means of an in-vitro assay of epidermal retraction. The potential role of keratin tonofilaments as piezoelectric and pyroelectric elements in the epidermis is introduced and the spatial alignment of these macromolecular arrays is demonstrated to be a function of physiological tensions. These findings are discussed in the context of noninvasive epidermal sensors utilized to understand mechanisms of sensory development and physiological regulation. Optoelectronic (infrared) imaging of the dorsal temperature field and the alteration in this field by treatment with epidermal growth factor are presented as examples of this methodologic approach. It is concluded that a detailed examination of the material and physical properties of mammalian epidermis is a reasonable goal of biosensor development and research. Hypothetically, such studies may reveal important molecular and cellular mechanisms by which sensory data are transmitted or transduced at the organism-environmental interface.

Optical radiation in modern medicine

PubMed Central

Sowa, Paweł; Rutkowska-Talipska, Joanna; Rutkowski, Krzysztof; Kosztyła-Hojna, Bożena

2013-01-01

Optical radiation extends between microwaves and X-rays of the electromagnetic radiation and includes ultraviolet (UV), visible light (VL) and infrared (IR) components. The dose of radiation that reaches the skin is influenced by the ozone layer, position of the Sun, latitude, altitude, cloud cover and ground reflections. The photobiological effects of UV, VL and IR bands depend on their wavelength, frequency and mechanism of action. They are modified by the thickness, structure, vasculature and pigmentation of skin's stratum corneum, epidermis and dermis. Following absorption, IR affects the body mainly through transfer of thermal energy to tissues. Visible light and skin interact either thermally or photochemically, whereas UV acts mainly photochemically. Optical radiation in the form of sunlight therapy had been used already in ancient times. Nowadays IR, VL and UV are widely applied in the therapy of allergic, dermatological, cardiovascular, respiratory, rheumatic, neonatal, pediatric and psychiatric disorders. PMID:24278082

Interaction of phloretin and 6-ketocholestanol with DPPC-liposomes as phospholipid model membranes.

PubMed

Auner, Barbara G; O'Neill, Michael A A; Valenta, Claudia; Hadgraft, Jonathan

2005-04-27

Phloretin and 6-ketocholestanol are penetration enhancers for percutaneous delivery of certain topically applied drugs. In the present study some physicochemical experiments have been performed to elucidate the mechanism of action of phloretin and 6-ketocholestanol. The penetration enhancing effect of phloretin and 6-ketocholestanol is believed to be due to their increase of the fluidity of the intercellular lipid bilayers of the stratum corneum. Phospholipid vesicles were chosen as a simple model to represent these bilayers. The effect of phloretin and 6-ketocholestanol on phase transition temperature and enthalpy was studied using differential scanning calorimetry. Beside of that the size of liposomes was monitored when the amount of penetration enhancer in the liposome preparation was changed. Addition of increasing amounts of phloretin and 6-ketocholestanol to the bilayer resulted in lowering of phase transition temperatures and increasing the enthalpy. Additionally the size of the liposomes was increased when penetration enhancer was added. The results suggest that phloretin as well as 6-ketocholestanol would interact with stratum corneum lipids in a similar manner, both reduce the diffusional resistance of the stratum corneum to drugs with balanced hydrophilic-lipophilic characteristics.

Quantitative characterization of chitosan in the skin by Fourier-transform infrared spectroscopic imaging and ninhydrin assay: application in transdermal sciences.

PubMed

Nawaz, A; Wong, T W

2016-07-01

The chitosan has been used as the primary excipient in transdermal particulate dosage form design. Its distribution pattern across the epidermis and dermis is not easily accessible through chemical assay and limited to radiolabelled molecules via quantitative autoradiography. This study explored Fourier-transform infrared spectroscopy imaging technique with built-in microscope as the means to examine chitosan molecular distribution over epidermis and dermis with the aid of histology operation. Fourier-transform infrared spectroscopy skin imaging was conducted using chitosan of varying molecular weights, deacetylation degrees, particle sizes and zeta potentials, obtained via microwave ligation of polymer chains at solution state. Both skin permeation and retention characteristics of chitosan increased with the use of smaller chitosan molecules with reduced acetyl content and size, and increased positive charge density. The ratio of epidermal to dermal chitosan content decreased with the use of these chitosan molecules as their accumulation in dermis (3.90% to 18.22%) was raised to a greater extent than epidermis (0.62% to 1.92%). A larger dermal chitosan accumulation nonetheless did not promote the transdermal polymer passage more than the epidermal chitosan. A small increase in epidermal chitosan content apparently could fluidize the stratum corneum and was more essential to dictate molecular permeation into dermis and systemic circulation. The histology technique aided Fourier-transform infrared spectroscopy imaging approach introduces a new dimension to the mechanistic aspect of chitosan in transdermal delivery. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

Effects of various vehicles on skin hydration in vivo.

PubMed

Wiedersberg, S; Leopold, C S; Guy, R H

2009-01-01

The stratum corneum, the outermost layer of the skin, regulates the passive loss of water to the environment. Furthermore, it is well accepted that drug penetration is influenced by skin hydration, which may be manipulated by the application of moisturizing or oleaginous vehicles. Measurements of transepidermal water loss (TEWL), and of skin hydration using a corneometer, were used to assess the effect of different vehicles on stratum corneum barrier function in vivo in human volunteers. A microemulsion significantly increased skin hydration relative to a reference vehicle based on medium chain triglycerides; in contrast, Transcutol(R) lowered skin hydration. TEWL measurements confirmed these observations. Copyright 2009 S. Karger AG, Basel.

Human Keratinocyte Growth and Differentiation on Acellular Porcine Dermal Matrix in relation to Wound Healing Potential

PubMed Central

Zajicek, Robert; Mandys, Vaclav; Mestak, Ondrej; Sevcik, Jan; Königova, Radana; Matouskova, Eva

2012-01-01

A number of implantable biomaterials derived from animal tissues are now used in modern surgery. Xe-Derma is a dry, sterile, acellular porcine dermis. It has a remarkable healing effect on burns and other wounds. Our hypothesis was that the natural biological structure of Xe-Derma plays an important role in keratinocyte proliferation and formation of epidermal architecture in vitro as well as in vivo. The bioactivity of Xe-Derma was studied by a cell culture assay. We analyzed growth and differentiation of human keratinocytes cultured in vitro on Xe-Derma, and we compared the results with formation of neoepidermis in the deep dermal wounds treated with Xe-Derma. Keratinocytes cultured on Xe-Derma submerged in the culture medium achieved confluence in 7–10 days. After lifting the cultures to the air-liquid interface, the keratinocytes were stratified and differentiated within one week, forming an epidermis with basal, spinous, granular, and stratum corneum layers. Immunohistochemical detection of high-molecular weight cytokeratins (HMW CKs), CD29, p63, and involucrin confirmed the similarity of organization and differentiation of the cultured epidermal cells to the normal epidermis. The results suggest that the firm natural structure of Xe-Derma stimulates proliferation and differentiation of human primary keratinocytes and by this way improves wound healing. PMID:22629190

Imaging-guided two-photon excitation-emission-matrix measurements of human skin tissues

NASA Astrophysics Data System (ADS)

Yu, Yingqiu; Lee, Anthony M. D.; Wang, Hequn; Tang, Shuo; Zhao, Jianhua; Lui, Harvey; Zeng, Haishan

2012-07-01

There are increased interests on using multiphoton imaging and spectroscopy for skin tissue characterization and diagnosis. However, most studies have been done with just a few excitation wavelengths. Our objective is to perform a systematic study of the two-photon fluorescence (TPF) properties of skin fluorophores, normal skin, and diseased skin tissues. A nonlinear excitation-emission-matrix (EEM) spectroscopy system with multiphoton imaging guidance was constructed. A tunable femtosecond laser was used to vary excitation wavelengths from 730 to 920 nm for EEM data acquisition. EEM measurements were performed on excised fresh normal skin tissues, seborrheic keratosis tissue samples, and skin fluorophores including: NADH, FAD, keratin, melanin, collagen, and elastin. We found that in the stratum corneum and upper epidermis of normal skin, the cells have large sizes and the TPF originates from keratin. In the lower epidermis, cells are smaller and TPF is dominated by NADH contributions. In the dermis, TPF is dominated by elastin components. The depth resolved EEM measurements also demonstrated that keratin structure has intruded into the middle sublayers of the epidermal part of the seborrheic keratosis lesion. These results suggest that the imaging guided TPF EEM spectroscopy provides useful information for the development of multiphoton clinical devices for skin disease diagnosis.

Cutaneous gene expression of plasmid DNA in excised human skin following delivery via microchannels created by radio frequency ablation.

PubMed

Birchall, James; Coulman, Sion; Anstey, Alexander; Gateley, Chris; Sweetland, Helen; Gershonowitz, Amikam; Neville, Lewis; Levin, Galit

2006-04-07

The skin is a valuable organ for the development and exploitation of gene medicines. Delivering genes to skin is restricted however by the physico-chemical properties of DNA and the stratum corneum (SC) barrier. In this study, we demonstrate the utility of an innovative technology that creates transient microconduits in human skin, allowing DNA delivery and resultant gene expression within the epidermis and dermis layers. The radio frequency (RF)-generated microchannels were of sufficient morphology and depth to permit the epidermal delivery of 100 nm diameter nanoparticles. Model fluorescent nanoparticles were used to confirm the capacity of the channels for augmenting diffusion of macromolecules through the SC. An ex vivo human organ culture model was used to establish the gene expression efficiency of a beta-galactosidase reporter plasmid DNA applied to ViaDerm treated skin. Skin treated with ViaDerm using 50 microm electrode arrays promoted intense levels of gene expression in the viable epidermis. The intensity and extent of gene expression was superior when ViaDerm was used following a prior surface application of the DNA formulation. In conclusion, the RF-microchannel generator (ViaDerm) creates microchannels amenable for delivery of nanoparticles and gene therapy vectors to the viable region of skin.

Skin permeation enhancement effects of the gel and whole-leaf materials of Aloe vera, Aloe marlothii and Aloe ferox.

PubMed

Fox, Lizelle T; Gerber, Minja; du Preez, Jan L; du Plessis, Jeanetta; Hamman, Josias H

2015-01-01

The aim of this study was to investigate the in-vitro permeation enhancement effects of the gel and whole-leaf materials of Aloe vera, Aloe marlothii and Aloe ferox using ketoprofen as a marker compound. The permeation studies were conducted across excised female abdominal skin in Franz diffusion cells, and the delivery of ketoprofen into the stratum corneum-epidermis and epidermis-dermis layers of the skin was investigated using a tape-stripping technique. A. vera gel showed the highest permeation-enhancing effect on ketoprofen (enhancement ratio or ER = 2.551) when compared with the control group, followed by A. marlothii gel (ER = 1.590) and A. ferox whole-leaf material (ER = 1.520). Non-linear curve fitting calculations indicated that the drug permeation-enhancing effect of A. vera gel can be attributed to an increased partitioning of the drug into the skin, while A. ferox whole leaf modified the diffusion characteristics of the skin for ketoprofen. The tape stripping results indicated that A. marlothii whole leaf delivered the highest concentration of the ketoprofen into the different skin layers. Of the selected aloe species investigated, A. vera gel material showed the highest potential as transdermal drug penetration enhancer across human skin. © 2014 Royal Pharmaceutical Society.

Human keratinocyte growth and differentiation on acellular porcine dermal matrix in relation to wound healing potential.

PubMed

Zajicek, Robert; Mandys, Vaclav; Mestak, Ondrej; Sevcik, Jan; Königova, Radana; Matouskova, Eva

2012-01-01

A number of implantable biomaterials derived from animal tissues are now used in modern surgery. Xe-Derma is a dry, sterile, acellular porcine dermis. It has a remarkable healing effect on burns and other wounds. Our hypothesis was that the natural biological structure of Xe-Derma plays an important role in keratinocyte proliferation and formation of epidermal architecture in vitro as well as in vivo. The bioactivity of Xe-Derma was studied by a cell culture assay. We analyzed growth and differentiation of human keratinocytes cultured in vitro on Xe-Derma, and we compared the results with formation of neoepidermis in the deep dermal wounds treated with Xe-Derma. Keratinocytes cultured on Xe-Derma submerged in the culture medium achieved confluence in 7-10 days. After lifting the cultures to the air-liquid interface, the keratinocytes were stratified and differentiated within one week, forming an epidermis with basal, spinous, granular, and stratum corneum layers. Immunohistochemical detection of high-molecular weight cytokeratins (HMW CKs), CD29, p63, and involucrin confirmed the similarity of organization and differentiation of the cultured epidermal cells to the normal epidermis. The results suggest that the firm natural structure of Xe-Derma stimulates proliferation and differentiation of human primary keratinocytes and by this way improves wound healing.

Development of skin structure and cutaneous water loss in nestling desert house sparrows from Saudi Arabia.

PubMed

Groff, Brandon; Muñoz-Garcia, Agustí; Yamaguchi, Mamoru; Williams, Joseph B

2007-06-01

The outer layer of the epidermis, the stratum corneum (SC), contains lipids and corneocytes, which together form layers that limit cutaneous water loss (CWL). We examined the development of structure of the SC and CWL in nestling House Sparrows (Passer domesticus) from Saudi Arabia. We measured CWL of nestlings, and characterized development of their epidermis using electron microscopy. We tested two antagonistic hypotheses, that CWL decreases as nestlings age, a response to increased thickness of SC, and an opposite idea that CWL increases as nestlings age even though the number of layers of the SC remains constant. CWL of nestling House Sparrows varied with developmental stages, in a non-linear fashion, but not significantly so. CWL of nestlings averaged 7.31+/-1.5 g H(2)O/(m(2) h), whereas for adults it was 4.95 g/(m(2) h); adult CWL was 67.7% that of nestlings. We found that morphology of the SC did not change linearly with age, but seemed to vary with developmental stage. CWL decreased as the SC thickness increased and as the total thickness of the corneocytes increased. Further, we found that CWL decreased as the thickness of the extracellular space increased, number of corneocytes increased, and proportion of the SC that is extracellular space increased.

Keratins K2 and K10 are essential for the epidermal integrity of plantar skin.

PubMed

Fischer, Heinz; Langbein, Lutz; Reichelt, Julia; Buchberger, Maria; Tschachler, Erwin; Eckhart, Leopold

2016-01-01

K1 and K2 are the main type II keratins in the suprabasal epidermis where each of them heterodimerizes with the type I keratin K10 to form intermediate filaments. In regions of the ears, tail, and soles of the mouse, only K2 is co-expressed with K10, suggesting that these keratins suffice to form a mechanically resilient cytoskeleton. To determine the effects of the suppression of both main keratins, K2 and K10, in the suprabasal plantar epidermis of the mouse. Krt2(-/-) Krt10(-/-) mice were generated by crossing Krt2(-/-) and Krt10(-/-) mice. Epidermal morphology of soles of hind-paws was examined macroscopically and histologically. Immunofluorescence analysis and quantitative PCR analysis were performed to analyze the expression of keratins in sole skin of wildtype and Krt2(-/-) Krt10(-/-) mice. Highly abundant proteins of the sole stratum corneum were determined by electrophoretic and chromatographic separation and subsequent mass spectrometry. K2 and K10 are the most prominent suprabasal keratins in normal mouse soles with the exception of the footpads where K1, K9 and K10 predominate. Mice lacking both K2 and K10 were viable and developed epidermal acanthosis and hyperkeratosis in inter-footpad epidermis of the soles. The expression of keratins K1, K9 and K16 was massively increased at the RNA and protein levels in the soles of Krt2(-/-) Krt10(-/-) mice. This study demonstrates that the loss of the main cytoskeletal components of plantar epidermis, i.e. K2 and K10, can be only partly compensated by the upregulation of other keratins. The thickening of the epidermis in the soles of Krt2(-/-) Krt10(-/-) mice may serve as a model for pathomechanistic aspects of palmoplantar keratoderma. Copyright © 2015. Published by Elsevier Ireland Ltd.

Tribology of bio-inspired nanowrinkled films on ultrasoft substrates.

PubMed

Lackner, Juergen M; Waldhauser, Wolfgang; Major, Lukasz; Teichert, Christian; Hartmann, Paul

2013-01-01

Biomimetic design of new materials uses nature as antetype, learning from billions of years of evolution. This work emphasizes the mechanical and tribological properties of skin, combining both hardness and wear resistance of its surface (the stratum corneum) with high elasticity of the bulk (epidermis, dermis, hypodermis). The key for combination of such opposite properties is wrinkling, being consequence of intrinsic stresses in the bulk (soft tissue): Tribological contact to counterparts below the stress threshold for tissue trauma occurs on the thick hard stratum corneum layer pads, while tensile loads smooth out wrinkles in between these pads. Similar mechanism offers high tribological resistance to hard films on soft, flexible polymers, which is shown for diamond-like carbon (DLC) and titanium nitride thin films on ultrasoft polyurethane and harder polycarbonate substrates. The choice of these two compared substrate materials will show that ultra-soft substrate materials are decisive for the distinct tribological material. Hierarchical wrinkled structures of films on these substrates are due to high intrinsic compressive stress, which evolves during high energetic film growth. Incremental relaxation of these stresses occurs by compound deformation of film and elastic substrate surface, appearing in hierarchical nano-wrinkles. Nano-wrinkled topographies enable high elastic deformability of thin hard films, while overstressing results in zigzag film fracture along larger hierarchical wrinkle structures. Tribologically, these fracture mechanisms are highly important for ploughing and sliding of sharp and flat counterparts on hard-coated ultra-soft substrates like polyurethane. Concentration of polyurethane deformation under the applied normal loads occurs below these zigzag cracks. Unloading closes these cracks again. Even cyclic testing do not lead to film delamination and retain low friction behavior, if the adhesion to the substrate is high and the initial

Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery.

PubMed

Szunerits, Sabine; Boukherroub, Rabah

2018-01-01

Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs), which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum , the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section "Frontiers in Bioengineering and Biotechnology," the advances in this field and the handful of

Structure of the integument of southern right whales, Eubalaena australis.

PubMed

Reeb, Desray; Best, Peter Barrington; Kidson, Susan Hillary

2007-06-01

Skin (integument) anatomy reflects adaptations to particular environments. It is hypothesized that cetacean (whale) integument will show unique anatomical adaptations to an aquatic environment, particularly regarding differences in temperature, density, and pressure. In this study, the gross and histological structure of the southern right whale integument is described and compared with terrestrial mammals and previous descriptions of mysticete (baleen whale) and odontocete (toothed whale) species. Samples were taken of the integument of 98 free-swimming southern right whales, Eubalaena australis, and examined by both light and electron microscopy. Results show that three epidermal layers are present, with the stratum corneum being parakeratotic in nature. As in bowhead whales, southern right whales possess an acanthotic epidermis and a notably thick hypodermis, with epidermal rods and extensive papillomatosis. However, unlike bowhead whales, southern right whales possess an uninterrupted hypodermal layer. Surprisingly, the integument of balaenids (right and bowhead mysticetes) in general is more like that of odontocetes than that of the more closely related balaenopterids (rorqual mysticetes). Similarities to odontocetes were found specifically in the collagen fibers in a fat-free zone of the reticular dermal layer and the elastic fibers in the dermal and hypodermal layers. Callosities, a distinctive feature of this genus, have a slightly thicker stratum corneum and are usually associated with hairs that have innervated and vascularized follicles. These hairs may function as vibrissae, thus aiding in aquatic foraging by allowing rapid detection of changes in prey density. Although the thick insulatory integument makes right whales bulky and slow-moving, it is an adaptation for living in cold water. Epidermal thickness, presence of epidermal rods, and callosities may act as barriers against mechanical injury from bodily contact with conspecifics or hard surfaces in

In vitro studies of cutaneous retention of magnetic nanoemulsion loaded with zinc phthalocyanine for synergic use in skin cancer treatment

NASA Astrophysics Data System (ADS)

Primo, Fernando L.; Rodrigues, Marcilene M. A.; Simioni, Andreza R.; Bentley, Maria V. L. B.; Morais, Paulo C.; Tedesco, Antonio C.

In this study was developed a new nano drug delivery system (NDDS) based on association of biodegradable surfactants with biocompatible magnetic fluid of maguemita citrate derivative. This formulation consists in a magnetic emulsion with nanostructured colloidal particles. Preliminary in vitro experiments showed that the formulation presents a great potential for synergic application in the topical release of photosensitizer drug (PS) and excellent target tissue properties in the photodynamic therapy (PDT) combined with hyperthermia (HPT) protocols. The physical chemistry characterization and in vitro assays were carried out by Zn(II) Phtalocyanine (ZnPc) photosensitizer incorporated into NDDS in the absence and the presence of magnetic fluid, showed good results and high biocompatibility. In vitro experiments were accomplished by tape-stripping protocols for quantification of drug association with different skin tissue layers. This technique is a classical method for analyses of drug release in stratum corneum and epidermis+ dermis skin layers. The NDDS formulations were applied directly in pig skin (tissue model) fixed in the cell's Franz device with receptor medium container with a PBS/EtOH 20% solution (10 mM, pH 7.4) at 37 °C. After 12 h of topical administration stratum corneum was removed from fifty tapes and the ZnPc retained was evaluated by solvent extraction in dimetil-sulphoxide under ultrasonic bath. These results indicated that magnetic nanoemulsion (MNE) increase the drug release on the deeper skin layers when compared with classical formulation in the absence of magnetic particles. This could be related with the increase of biocompatibility of NDDS due to the great affinity for the polar extracelullar matrix in the skin and also for the increase in the drug partition inside of corneocites wall.

Structural changes in the skin of hairless mice following exposure to sulfur mustard correlate with inflammation and DNA damage.

PubMed

Joseph, Laurie B; Gerecke, Donald R; Heck, Diane E; Black, Adrienne T; Sinko, Patrick J; Cervelli, Jessica A; Casillas, Robert P; Babin, Michael C; Laskin, Debra L; Laskin, Jeffrey D

2011-10-01

Sulfur mustard (SM, bis(2-chloroethyl)sulfide) is a bifunctional alkylating agent that causes dermal inflammation, edema and blistering. To investigate the pathogenesis of SM-induced injury, we used a vapor cup model which provides an occlusive environment in which SM is in constant contact with the skin. The dorsal skin of SKH-1 hairless mice was exposed to saturated SM vapor or air control. Histopathological changes, inflammatory markers and DNA damage were analyzed 1-14 days later. After 1 day, SM caused epidermal thinning, stratum corneum shedding, basal cell karyolysis, hemorrhage and macrophage and neutrophil accumulation in the dermis. Cleaved caspase-3 and phosphorylated histone 2A.X (phospho-H2A.X), markers of apoptosis and DNA damage, respectively, were increased whereas proliferating cell nuclear antigen (PCNA) was down-regulated after SM exposure. By 3 days, epithelial cell hypertrophy, edema, parakeratosis and loss of epidermal structures were noted. Enzymes generating pro-inflammatory mediators including myeloperoxidase and cyclooxygenase-2 were upregulated. After 7 days, keratin-10, a differentiation marker, was evident in the stratum corneum. This was associated with an underlying eschar, as neoepidermis began to migrate at the wound edges. Trichrome staining revealed increased collagen deposition in the dermis. PCNA expression in the epidermis was correlated with hyperplasia, hyperkeratosis, and parakeratosis. By 14 days, there was epidermal regeneration with extensive hyperplasia, and reduced expression of cleaved caspase-3, cyclooxygenase-2 and phospho-H2A.X. These findings are consistent with the pathophysiology of SM-induced skin injury in humans suggesting that the hairless mouse can be used to investigate the dermatoxicity of vesicants and the potential efficacy of countermeasures. Copyright © 2011 Elsevier Inc. All rights reserved.

Tribology of bio-inspired nanowrinkled films on ultrasoft substrates

PubMed Central

Lackner, Juergen M.; Waldhauser, Wolfgang; Major, Lukasz; Teichert, Christian; Hartmann, Paul

2013-01-01

Biomimetic design of new materials uses nature as antetype, learning from billions of years of evolution. This work emphasizes the mechanical and tribological properties of skin, combining both hardness and wear resistance of its surface (the stratum corneum) with high elasticity of the bulk (epidermis, dermis, hypodermis). The key for combination of such opposite properties is wrinkling, being consequence of intrinsic stresses in the bulk (soft tissue): Tribological contact to counterparts below the stress threshold for tissue trauma occurs on the thick hard stratum corneum layer pads, while tensile loads smooth out wrinkles in between these pads. Similar mechanism offers high tribological resistance to hard films on soft, flexible polymers, which is shown for diamond-like carbon (DLC) and titanium nitride thin films on ultrasoft polyurethane and harder polycarbonate substrates. The choice of these two compared substrate materials will show that ultra-soft substrate materials are decisive for the distinct tribological material. Hierarchical wrinkled structures of films on these substrates are due to high intrinsic compressive stress, which evolves during high energetic film growth. Incremental relaxation of these stresses occurs by compound deformation of film and elastic substrate surface, appearing in hierarchical nano-wrinkles. Nano-wrinkled topographies enable high elastic deformability of thin hard films, while overstressing results in zigzag film fracture along larger hierarchical wrinkle structures. Tribologically, these fracture mechanisms are highly important for ploughing and sliding of sharp and flat counterparts on hard-coated ultra-soft substrates like polyurethane. Concentration of polyurethane deformation under the applied normal loads occurs below these zigzag cracks. Unloading closes these cracks again. Even cyclic testing do not lead to film delamination and retain low friction behavior, if the adhesion to the substrate is high and the initial

Contribution of glue layer into epidermis sample fluorescence dynamics

NASA Astrophysics Data System (ADS)

Salomatina, Elena V.; Chernova, Svetlana P.; Pravdin, Alexander B.

2000-04-01

In this work, the temporal behavior of autofluorescence of epidermis samples under UV-irradiation has ben studied. The samples were prepared using surface epidermis stripping technique. Fluorescence spectra and kinetic curves of fluorescence intensity have been obtained. It has been concluded that the glue composition used allows the measurement of epidermis fluorescence dynamics with the first 60 min of experiment.

Hydrogel increases localized transport regions and skin permeability during low frequency ultrasound treatment

NASA Astrophysics Data System (ADS)

Pereira, Tatiana Aparecida; Ramos, Danielle Nishida; Lopez, Renata F. V.

2017-03-01

Low frequency ultrasound (LFU) enhances skin permeability via the formation of heterogeneous localized transport regions (LTRs). In this work, hydrogels with different zeta potentials were used as the coupling medium for LFU to investigate their contribution to LTR patterns and to the skin penetration of two model drugs, calcein and doxorubicin (DOX). When hydrogels were used, LTRs covering at least a 3-fold greater skin area were observed compared to those resulting from traditional LFU treatment and sodium lauryl sulfate. More LTRs resulted in an enhancement of calcein skin permeation. The zeta potential of the hydrogels affected the skin penetration of the positively charged DOX; the cationic coupling medium decreased the DOX recovered from the viable epidermis by 2.8-fold, whereas the anionic coupling medium increased the DOX accumulation in the stratum corneum by 4.4-fold. Therefore, LFU/hydrogel treatment increases LTRs areas and can target ionized drugs to specific skin layers depending on the zeta potential of the coupling medium.

Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery.

PubMed

Tan, Qi; Liu, Weidong; Guo, Chenyu; Zhai, Guangxi

2011-01-01

The purpose of this study was to investigate lecithin-chitosan nanoparticles as a topical delivery system for quercetin. Tocopheryl propylene glycol succinate was chosen to be the surfactant for the nanosystem. The mean particle size of the nanoparticles was 95.3 nm, and the entrapment efficiency and drug loading for quercetin were 48.5% and 2.45%, respectively. Topical delivery in vitro and in vivo of the quercetin-loaded nanoparticles was evaluated using quercetin propylene glycol solution as the control. Compared with quercetin solution, the quercetin-loaded nanoparticles showed higher permeation ability, and significantly increased accumulation of quercetin in the skin, especially in the epidermis. Microstructure observation of the skin surface after administration indicated that the interaction between ingredients of the nanoparticles and the skin surface markedly changed the morphology of the stratum corneum and disrupted the corneocyte layers, thus facilitating the permeation and accumulation of quercetin in skin. Lecithin-chitosan nanoparticles are a promising carrier for topical delivery of quercetin.

Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery

PubMed Central

Tan, Qi; Liu, Weidong; Guo, Chenyu; Zhai, Guangxi

2011-01-01

Background The purpose of this study was to investigate lecithin-chitosan nanoparticles as a topical delivery system for quercetin. Methods Tocopheryl propylene glycol succinate was chosen to be the surfactant for the nanosystem. The mean particle size of the nanoparticles was 95.3 nm, and the entrapment efficiency and drug loading for quercetin were 48.5% and 2.45%, respectively. Topical delivery in vitro and in vivo of the quercetin-loaded nanoparticles was evaluated using quercetin propylene glycol solution as the control. Results Compared with quercetin solution, the quercetin-loaded nanoparticles showed higher permeation ability, and significantly increased accumulation of quercetin in the skin, especially in the epidermis. Microstructure observation of the skin surface after administration indicated that the interaction between ingredients of the nanoparticles and the skin surface markedly changed the morphology of the stratum corneum and disrupted the corneocyte layers, thus facilitating the permeation and accumulation of quercetin in skin. Conclusion Lecithin-chitosan nanoparticles are a promising carrier for topical delivery of quercetin. PMID:21904452

Iron deposition in skin of patients with haemochromatosis

NASA Astrophysics Data System (ADS)

Pinheiro, T.; Silva, J. N.; Alves, L. C.; Filipe, P.

2003-09-01

Haemochromatosis is the most common inherited liver disease in Caucasians and the most common autosomal recessive genetic disorder. It is characterized by inappropriately high iron absorption resulting in progressive iron overload in parenchymal organs such as liver, heart, pancreas, pituitary, joints, and skin. Upon early detection, haemochromatosis can be a manageable chronic disease but, if undetected, is potentially fatal. Skin biopsies were obtained from patients and from healthy donors. Images of the elemental distributions in skin were obtained using nuclear microscopy techniques (nuclear microprobe, NMP). Elemental profiles along skin, and intra-, and extra-cellular iron concentrations, were determined. Results for patients with haemochromatosis were cross-examined with morphologic features and with data obtained for healthy skin. Skin iron content is much increased in patients with haemochromatosis when compared with healthy subjects. Extensive iron deposits are observed at dermis, at the dermo-epidermal interface, at upper epidermis layers and at stratum corneum. Iron deposition was observed preferentially at cell boundaries or at the interstitial matrix.

Qualitative and Quantitative Study of the Potential of Lipid Nanocapsules of One Hundred Twenty Nanometers for the Topical Administration of Hydrophobic Molecules.

PubMed

Nguyen, Hoang Truc Phuong; Munnier, Emilie; Perse, Xavier; Vial, Francis; Yvergnaux, Florent; Perrier, Thomas; Soucé, Martin; Chourpa, Igor

2016-10-01

In this study, we evaluated the potential of lipid nanocapsules (LNC) of 120 nm as drug nanocarriers to treat skin diseases. As a model molecule, we encapsulated the fluorescent dye curcumin, which also is an antioxidant. Curcumin-loaded LNC showed interesting antioxidant properties and a low toxicity on human skin cells. The penetration of curcumin in the skin was determined by 2 complementary methods: high performance liquid chromatography was used to measure total curcumin accumulation in the skin, whereas fluorescence confocal spectral imaging of skin sections showed that curcumin preferentially accumulates in the stratum corneum and the viable epidermis. These results confirm that LNC of a size above 100 nm can vectorize hydrophobic compounds to the keratinocytes without transdermal delivery. They also demonstrate the interest of combining 2 analytical methods when studying the skin penetration of nanovectorized molecules. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Electrical measurement of the hydration state of the skin surface in vivo.

PubMed

Tagami, H

2014-09-01

Healthy skin surface is smooth and soft, because it is covered by the properly hydrated stratum corneum (SC), an extremely thin and soft barrier membrane produced by the underlying normal epidermis. By contrast, the skin surfaces covering pathological lesions exhibit dry and scaly changes and the SC shows poor barrier function. The SC barrier function has been assessed in vivo by instrumentally measuring transepidermal water loss (TEWL). However, there was a lack of any appropriate method for evaluating the hydration state of the skin surface in vivo until 1980 when we reported the feasibility of employing high-frequency conductance or capacitance to evaluate it quickly and accurately. With such measurements, we can assess easily the moisturizing efficacy of various topical agents in vivo as well as the distribution pattern of water in the SC by combining it with a serial tape-stripping procedure of the skin surface. © 2014 The Author BJD © 2014 British Association of Dermatologists.

Assessment of transcutaneous vaccine delivery by optical coherence tomography Assessment of transcutaneous vaccine delivery by OCT

NASA Astrophysics Data System (ADS)

Kamali, T.; Doronin, A.; Rattanapak, T.; Hook, S.; Meglinski, I.

2012-08-01

Immunization is one of the most efficient and cost-effective means for the prevention of diseases. The latest trend for inducing protective immunity is topical application of vaccines to intact skin rather than invasive administration via injection. Apart from being a non-invasive route of drug delivery, skin itself also offers advantages through the presence of cells of the immune system in both the dermis and epidermis. However, vaccine penetration through the outermost layers of skin is limited by the barrier provided by the Stratum corneum. In the current study utilizing conventional Optical Coherence Tomography (OCT) we investigate the transcutaneous delivery of a nano- particulate peptide vaccine into mouse skin in vivo. We demonstrate that a front of molecular diffusion within the skin can be clearly observed by using cross-correlations of successive 2D OCT images. Thus, OCT provides a unique tool for quantitative assessment of dynamics of diffusion of drugs, target compounds, analytes, cosmetics and various chemical agents in biological tissues in vivo.

AKT1 provides an essential survival signal required for differentiation and stratification of primary human keratinocytes.

PubMed

Thrash, Barry R; Menges, Craig W; Pierce, Robert H; McCance, Dennis J

2006-04-28

Keratinocyte differentiation and stratification are complex processes involving multiple signaling pathways, which convert a basal proliferative cell into an inviable rigid squame. Loss of attachment to the basement membrane triggers keratinocyte differentiation, while in other epithelial cells, detachment from the extracellular matrix leads to rapid programmed cell death or anoikis. The potential role of AKT in providing a survival signal necessary for stratification and differentiation of primary human keratinocytes was investigated. AKT activity increased during keratinocyte differentiation and was attributed to the specific activation of AKT1 and AKT2. Targeted reduction of AKT1 expression, but not AKT2, by RNA interference resulted in an abnormal epidermis in organotypic skin cultures with a thin parabasal region and a pronounced but disorganized cornified layer. This abnormal stratification was due to significant cell death in the suprabasal layers and was alleviated by caspase inhibition. Normal expression patterns of both early and late markers of keratinocyte differentiation were also disrupted, producing a poorly developed stratum corneum.

The effect of mangiferin on skin: Penetration, permeation and inhibition of ECM enzymes.

PubMed

Ochocka, Renata; Hering, Anna; Stefanowicz-Hajduk, Justyna; Cal, Krzysztof; Barańska, Helena

2017-01-01

Mangiferin (2-C-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone) is a polyphenol with strong antioxidant properties. Mangiferin is obtained from the mango tree (Mangifera indica L., Anacardiaceae). It has been proven that mangiferin exhibits many pharmacological activities. The aim of this study was to analyze the penetration of mangiferin into the human skin and through the skin. According to our knowledge, skin penetration and permeation studies of mangiferin have not been analyzed so far. Additionally, the influence of mangiferin on two Extracellular Matrix Enzymes (ECM): collagenase and elastase, was evaluated for the first time. It has been indicated that mangiferin is able to permeate the stratum corneum and penetrate into the epidermis and dermis in comparable amounts. For confirmation of the obtained results, fluorescence microscopy was successfully utilized. The analysis revealed the capability of mangiferin to reversibly inhibit elastase and collagenase activity. The mechanism of mangiferin interaction with both enzymes was estimated as a noncompetitive inhibition.

The effect of mangiferin on skin: Penetration, permeation and inhibition of ECM enzymes

PubMed Central

Hering, Anna; Stefanowicz–Hajduk, Justyna; Cal, Krzysztof; Barańska, Helena

2017-01-01

Mangiferin (2-C-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone) is a polyphenol with strong antioxidant properties. Mangiferin is obtained from the mango tree (Mangifera indica L., Anacardiaceae). It has been proven that mangiferin exhibits many pharmacological activities. The aim of this study was to analyze the penetration of mangiferin into the human skin and through the skin. According to our knowledge, skin penetration and permeation studies of mangiferin have not been analyzed so far. Additionally, the influence of mangiferin on two Extracellular Matrix Enzymes (ECM): collagenase and elastase, was evaluated for the first time. It has been indicated that mangiferin is able to permeate the stratum corneum and penetrate into the epidermis and dermis in comparable amounts. For confirmation of the obtained results, fluorescence microscopy was successfully utilized. The analysis revealed the capability of mangiferin to reversibly inhibit elastase and collagenase activity. The mechanism of mangiferin interaction with both enzymes was estimated as a noncompetitive inhibition. PMID:28750062

Multiple-reflection model of human skin and estimation of pigment concentrations

NASA Astrophysics Data System (ADS)

Ohtsuki, Rie; Tominaga, Shoji; Tanno, Osamu

2012-07-01

We describe a new method for estimating the concentrations of pigments in the human skin using surface spectral reflectance. We derive an equation that expresses the surface spectral reflectance of the human skin. First, we propose an optical model of the human skin that accounts for the stratum corneum. We also consider the difference between the scattering coefficient of the epidermis and that of the dermis. We then derive an equation by applying the Kubelka-Munk theory to an optical model of the human skin. Unlike a model developed in a recent study, the present equation considers pigments as well as multiple reflections and the thicknesses of the skin layers as factors that affect the color of the human skin. In two experiments, we estimate the pigment concentrations using the measured surface spectral reflectances. Finally, we confirm the feasibility of the concentrations estimated by the proposed method by evaluating the estimated pigment concentrations in the skin.

A Homozygous Missense Mutation in TGM5 Abolishes Epidermal Transglutaminase 5 Activity and Causes Acral Peeling Skin Syndrome

PubMed Central

Cassidy, Andrew J.; van Steensel, Maurice A. M.; Steijlen, Peter M.; van Geel, Michel; Velden, Jaap van der; Morley, Susan M.; Terrinoni, Alessandro; Melino, Gerry; Candi, Eleonora; McLean, W. H. Irwin

2005-01-01

Peeling skin syndrome is an autosomal recessive genodermatosis characterized by the shedding of the outer epidermis. In the acral form, the dorsa of the hands and feet are predominantly affected. Ultrastructural analysis has revealed tissue separation at the junction between the granular cells and the stratum corneum in the outer epidermis. Genomewide linkage analysis in a consanguineous Dutch kindred mapped the gene to 15q15.2 in the interval between markers D15S1040 and D15S1016. Two homozygous missense mutations, T109M and G113C, were found in TGM5, which encodes transglutaminase 5 (TG5), in all affected persons in two unrelated families. The mutation was present on the same haplotype in both kindreds, indicating a probable ancestral mutation. TG5 is strongly expressed in the epidermal granular cells, where it cross-links a variety of structural proteins in the terminal differentiation of the epidermis to form the cornified cell envelope. An established, in vitro, biochemical cross-linking assay revealed that, although T109M is not pathogenic, G113C completely abolishes TG5 activity. Three-dimensional modeling of TG5 showed that G113C lies close to the catalytic domain, and, furthermore, that this glycine residue is conserved in all known transglutaminases, which is consistent with pathogenicity. Other families with more-widespread peeling skin phenotypes lacked TGM5 mutations. This study identifies the first causative gene in this heterogeneous group of skin disorders and demonstrates that the protein cross-linking function performed by TG5 is vital for maintaining cell-cell adhesion between the outermost layers of the epidermis. PMID:16380904

Development of a rate model to investigate contributions of anatomic and physiologic determinants of in vivo skin permeation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fleischer, N.M.

The skin is a heterogeneous, bi-directional impediment to chemical flux, in which the stratum corneum is a major, though not the sole, rate-limiting barrier layer to permeation. Systemic toxicity following dermal exposure to environmental chemicals and use of skin as a portal for systemic administration of drugs have led to extensive investigations of the inward flux of xenobiotics applied to the outer surface of skin. Those investigations mainly utilized in vitro experimental systems that were limited by the absence of normal physiologic functions. The objective of the present research was to investigate an in vivo skin permeation model system thatmore » was sensitive to perturbations of skin capillary physiology and stratum corneum. A [open quotes]fuzzy[close quotes] rat model system was devised that employed outward cutaneous migration of a systemically administered permeation probe, isoflurane. Specially devised, transdermal vapor collection devices were used to capture the outward flux of isoflurane through the skin. Isoflurane flux measurements, coupled with blood isoflurane concentrations, were used to calculate cutaneous permeability coefficients (K[sub p]) of isolflurane, as an index of permeation, under various conditions of normal or perturbed cutaneous physiologic states. Physiologic perturbations were performed to test the sensitivity of the model system to detect effects of minoxidil-mediated vasodilation, phenylephrine-mediated vasoconstriction, and leukotriene D[sub 4]-mediated increased capillary permeability on the outward flux of isoflurane. Tape stripping and topical ether-ethanol application produced either physical removal or chemical disruption of the stratum corneum, respectively. Minoxidil, leukotriene D[sub 4], tape stripping of stratum corneum, and topical ether-ethanol experiments produced statistically significant increases (52 to 193%) in the K[sub p's], while phenylephrine had no significant effect on isoflurane permeation.« less

Microfabrication of individual 200 microm diameter transdermal microconduits using high voltage pulsing in salicylic acid and benzoic acid.

PubMed

Ilic, L; Gowrishankar, T R; Vaughan, T E; Herndon, T O; Weaver, J C

2001-01-01

We describe an extension of semiconductor fabrication methods that creates individual approximately 200 microm diameter aqueous pathways through human stratum corneum at predetermined sites. Our hypothesis is that spatially localized electroporation of the multilamellar lipid bilayer membranes provides rapid delivery of salicylic acid to the keratin within corneocytes, leading to localized keratin disruption and then to a microconduit. A microconduit penetrating the isolated stratum corneum supports a volumetric flow of order 0.01 ml per s with a pressure difference of only 0.01 atm (about 10(2) Pa). This study provides a method for rapidly microengineering a pathway in the skin to interface future devices for transdermal drug delivery and sampling of biologically relevant fluids.

Mechanism and determinants of nanoparticle penetration through human skin

NASA Astrophysics Data System (ADS)

Labouta, Hagar I.; El-Khordagui, Labiba K.; Kraus, Tobias; Schneider, Marc

2011-12-01

The ability of nanoparticles to penetrate the stratum corneum was the focus of several studies. Yet, there are controversial issues available for particle penetration due to different experimental setups. Meanwhile, there is little known about the mechanism and determinants of their penetration. In this paper the penetration of four model gold nanoparticles of diameter 6 and 15 nm, differing in surface polarity and the nature of the vehicle, through human skin was studied using multiphoton microscopy. This is in an attempt to profoundly investigate the parameters governing particle penetration through human skin. Our results imply that nanoparticles at this size range permeate the stratum corneum in a similar manner to drug molecules, mainly through the intercellular pathways. However, due to their particulate nature, permeation is also dependent on the complex microstructure of the stratum corneum with its tortuous aqueous and lipidic channels, as shown from our experiments performed using skin of different grades of barrier integrity. The vehicle (toluene-versus-water) had a minimal effect on skin penetration of gold nanoparticles. Other considerations in setting up a penetration experiment for nanoparticles were also studied. The results obtained are important for designing a new transdermal carrier and for a basic understanding of skin-nanoparticle interaction.

Minoxidil Skin Delivery from Nanoemulsion Formulations Containing Eucalyptol or Oleic Acid: Enhanced Diffusivity and Follicular Targeting

PubMed Central

Abd, Eman; Benson, Heather A. E.; Roberts, Michael S.; Grice, Jeffrey E.

2018-01-01

In this work, we examined enhanced skin delivery of minoxidil applied in nanoemulsions incorporating skin penetration enhancers. Aliquots of fully characterized oil-in-water nanoemulsions (1 mL), containing minoxidil (2%) and the skin penetration enhancer oleic acid or eucalyptol as oil phases, were applied to full-thickness excised human skin in Franz diffusion cells, while aqueous solutions (1 mL) containing minoxidil were used as controls. Minoxidil in the stratum corneum (SC), hair follicles, deeper skin layers, and flux through the skin over 24 h was determined, as well as minoxidil solubility in the formulations and in the SC. The nanoemulsions significantly enhanced the permeation of minoxidil through skin compared with control solutions. The eucalyptol formulations (NE) promoted minoxidil retention in the SC and deeper skin layers more than did the oleic acid formulations, while the oleic acid formulations (NO) gave the greatest hair follicle penetration. Minoxidil maximum flux enhancement was associated with increases in both minoxidil SC solubility and skin diffusivity in both nanoemulsion systems. The mechanism of enhancement appeared to be driven largely by increased diffusivity, rather than increased partitioning into the stratum corneum, supporting the concept of enhanced fluidity and disruption of stratum corneum lipids. PMID:29370122

Dodecyl Amino Glucoside Enhances Transdermal and Topical Drug Delivery via Reversible Interaction with Skin Barrier Lipids.

PubMed

Kopečná, Monika; Macháček, Miloslav; Prchalová, Eva; Štěpánek, Petr; Drašar, Pavel; Kotora, Martin; Vávrová, Kateřina

2017-03-01

Skin permeation/penetration enhancers are substances that enable drug delivery through or into the skin. To search for new enhancers with high but reversible activity and acceptable toxicity, we synthesized a series of D-glucose derivatives, both hydrophilic and amphiphilic. Initial evaluation of the ability of these sugar derivatives to increase permeation and penetration of theophylline through/into human skin compared with a control (no enhancer) or sorbitan monolaurate (Span 20; positive control) revealed dodecyl 6-amino-6-deoxy-α-D-glucopyranoside 5 as a promising enhancer. Furthermore, this amino sugar 5 increased epidermal concentration of a highly hydrophilic antiviral cidofovir by a factor of 7. The effect of compound 5 on skin electrical impedance suggested its direct interaction with the skin barrier. Infrared spectroscopy of isolated stratum corneum revealed no effect of enhancer 5 on the stratum corneum proteins but an overall decrease in the lipid chain order. The enhancer showed acceptable toxicity on HaCaT keratinocyte and 3T3 fibroblast cell lines. Finally, transepidermal water loss returned to baseline values after enhancer 5 had been removed from the skin. Compound 5, a dodecyl amino glucoside, is a promising enhancer that acts through a reversible interaction with the stratum corneum lipids.

Chemical peeling by SA-PEG remodels photo-damaged skin: suppressing p53 expression and normalizing keratinocyte differentiation.

PubMed

Dainichi, Teruki; Amano, Satoshi; Matsunaga, Yukiko; Iriyama, Shunsuke; Hirao, Tetsuji; Hariya, Takeshi; Hibino, Toshihiko; Katagiri, Chika; Takahashi, Motoji; Ueda, Setsuko; Furue, Masutaka

2006-02-01

Chemical peeling with salicylic acid in polyethylene glycol vehicle (SA-PEG), which specifically acts on the stratum corneum, suppresses the development of skin tumors in UVB-irradiated hairless mice. To elucidate the mechanism through which chemical peeling with SA-PEG suppresses skin tumor development, the effects of chemical peeling on photodamaged keratinocytes and cornified envelopes (CEs) were evaluated in vivo. Among UVB-irradiated hairless mice, the structural atypia and expression of p53 protein in keratinocytes induced by UVB irradiation were intensely suppressed in the SA-PEG-treated mice 28 days after the start of weekly SA-PEG treatments when compared to that in the control UVB-irradiated mice. Incomplete expression of filaggrin and loricrin in keratinocytes from the control mice was also improved in keratinocytes from the SA-PEG-treated mice. In photo-exposed human facial skin, immature CEs were replaced with mature CEs 4 weeks after treatment with SA-PEG. Restoration of photodamaged stratum corneum by treatment with SA-PEG, which may affect remodeling of the structural environment of the keratinocytes, involved the normalization of keratinocyte differentiation and suppression of skin tumor development. These results suggest that the stratum corneum plays a protective role against carcinogenesis, and provide a novel strategy for the prevention of photo-induced skin tumors.

Topical bioavailability of diclofenac from locally-acting, dermatological formulations.

PubMed

Cordery, S F; Pensado, A; Chiu, W S; Shehab, M Z; Bunge, A L; Delgado-Charro, M B; Guy, R H

2017-08-30

Assessment of the bioavailability of topically applied drugs designed to act within or beneath the skin is a challenging objective. A number of different, but potentially complementary, techniques are under evaluation. The objective of this work was to evaluate in vitro skin penetration and stratum corneum tape-stripping in vivo as tools with which to measure topical diclofenac bioavailability from three approved and commercialized products (two gels and one solution). Drug uptake into, and its subsequent clearance from, the stratum corneum of human volunteers was used to estimate the input rate of diclofenac into the viable skin layers. This flux was compared to that measured across excised porcine skin in conventional diffusion cells. Both techniques clearly demonstrated (a) the superiority in terms of drug delivery from the solution, and (b) that the two gels performed similarly. There was qualitative and, importantly, quantitative agreement between the in vitro and in vivo measurements of drug flux into and beyond the viable skin. Evidence is therefore presented to support an in vivo - in vitro correlation between methods to assess topical drug bioavailability. The potential value of the stratum corneum tape-stripping technique to quantify drug delivery into (epi)dermal and subcutaneous tissue beneath the barrier is demonstrated. Copyright © 2017 Elsevier B.V. All rights reserved.

The Effects of Judgment-Based Stratum Classifications on the Efficiency of Stratum Scored CATs.

ERIC Educational Resources Information Center

Finney, Sara J.; Smith, Russell W.; Wise, Steven L.

Two operational item pools were used to investigate the performance of stratum computerized adaptive tests (CATs) when items were assigned to strata based on empirical estimates of item difficulty or human judgments of item difficulty. Items from the first data set consisted of 54 5-option multiple choice items from a form of the ACT mathematics…

Alpha- and beta-keratins of the snake epidermis.

PubMed

Toni, Mattia; Alibardi, Lorenzo

2007-01-01

Snake scales contain specialized hard keratins (beta-keratins) and alpha- or cyto-keratins in their epidermis. The number, isoelectric point, and the evolution of these proteins in snakes and their similarity with those of other vertebrates are not known. In the present study, alpha- and beta-keratins of snake molts and of the whole epidermis have been studied by using two-dimensional electrophoresis and immunocytochemistry. Specific keratins in snake epidermis have been identified by using antibodies that recognize acidic and basic cytokeratins and avian or lizard scale beta-keratin. Alpha keratins of 40-70 kDa and isoelectric point (pI) at 4.5-7.0 are present in molts. The study suggests that cytokeratins in snakes are acidic or neutral, in contrast to mammals and birds where basic keratins are also present. Beta keratins of 10-15 kDa and a pI of 6.5-8.5 are found in molts. Some beta-keratins appear as basic proteins (pI 8.2) comparable to those present in the epidermis of other reptiles. Some basic "beta-keratins" associate with cytokeratins as matrix proteins and replace cytokeratins forming the corneous material of the mature beta-layer of snake scales, as in other reptiles. The study also suggests that more forms of beta-keratins (more than three different types) are present in the epidermis of snakes.

Sensitivity of FIA Volume Estimates to Changes in Stratum Weights and Number of Strata

Treesearch

James A. Westfall; Michael Hoppus

2005-01-01

In the Northeast region, the USDA Forest Service Forest Inventory and Analysis (FIA) program utilizes stratified sampling techniques to improve the precision of population estimates. Recently, interpretation of aerial photographs was replaced with classified remotely sensed imagery to determine stratum weights and plot stratum assignments. However, stratum weights...

Stratum variance estimation for sample allocation in crop surveys. [Great Plains Corridor

NASA Technical Reports Server (NTRS)

Perry, C. R., Jr.; Chhikara, R. S. (Principal Investigator)

1980-01-01

The problem of determining stratum variances needed in achieving an optimum sample allocation for crop surveys by remote sensing is investigated by considering an approach based on the concept of stratum variance as a function of the sampling unit size. A methodology using the existing and easily available information of historical crop statistics is developed for obtaining initial estimates of tratum variances. The procedure is applied to estimate stratum variances for wheat in the U.S. Great Plains and is evaluated based on the numerical results thus obtained. It is shown that the proposed technique is viable and performs satisfactorily, with the use of a conservative value for the field size and the crop statistics from the small political subdivision level, when the estimated stratum variances were compared to those obtained using the LANDSAT data.

The effects of aromatherapy on pruritus in patients undergoing hemodialysis.

PubMed

Ro, You-Ja; Ha, Hyae-Chung; Kim, Chun-Gill; Yeom, Hye-A

2002-08-01

This study was designed to investigate the effects of aromatherapy on pruritus in patients with chronic renal failure undergoing hemodialysis. The participants were 29 adult patients living in Seoul, Korea. Thirteen patients were assigned to the experimental group and received the aromatherapy massage on the arm 3 times a week for 4 weeks. Pruritus score, skin pH, stratum corneum hydration, and pruritus-related biochemical markers were measured before and after the treatment. The results showed that pruritus score was significantly decreased after aromatherapy. Skin pH showed no significant changes in either group while stratum corneum hydration increased significantly in the experimental group after aromatherapy. The results support the use aromatherapy as a useful and effective method of managing pruritus in patients undergoing hemodialysis.

Transdermal drug delivery: from micro to nano

NASA Astrophysics Data System (ADS)

Pegoraro, Carla; MacNeil, Sheila; Battaglia, Giuseppe

2012-03-01

Delivery across skin offers many advantages compared to oral or intravenous routes of drug administration. Skin however is highly impermeable to most molecules on the basis of size, hydrophilicity, lipophilicity and charge. For this reason it is often necessary to temporarily alter the barrier properties of skin for effective administration. This can be done by applying chemical enhancers, which alter the lipid structure of the top layer of skin (the stratum corneum, SC), by applying external forces such as electric currents and ultrasounds, by bypassing the stratum corneum via minimally invasive microneedles or by using nano-delivery vehicles that can cross and deliver their payload to the deeper layers of skin. Here we present a critical summary of the latest technologies used to increase transdermal delivery.

Cyanoacrylate Skin Surface Stripping and the 3S-Biokit Advent in Tropical Dermatology: A Look from Liège

PubMed Central

Piérard, Gérald E.; Piérard-Franchimont, Claudine; Paquet, Philippe; Hermanns-Lê, Trinh; Delvenne, Philippe

2014-01-01

In the dermatopathology field, some simple available laboratory tests require minimum equipment for establishing a diagnosis. Among them, the cyanoacrylate skin surface stripping (CSSS), formerly named skin surface biopsy or follicular biopsy, represents a convenient low cost procedure. It is a minimally invasive method collecting a continuous sheet of stratum corneum and horny follicular casts. In the vast majority of cases, it is painless and is unassociated with adverse events. CSSS can be performed in subjects of any age. The method has a number of applications in diagnostic dermatopathology and cosmetology, as well as in experimental dermatology settings. A series of derived analytic procedures include xerosis grading, comedometry, corneofungimetry, corneodynamics of stratum corneum renewal, corneomelametry, corneosurfametry, and corneoxenometry. PMID:25177726

Trans-resveratrol and beta-carotene from sunscreens penetrate viable skin layers and reduce cutaneous penetration of UV-filters.

PubMed

Freitas, J V; Praça, F S G; Bentley, M V L B; Gaspar, L R

2015-04-30

Cutaneous permeation is a critical parameter when topical application of sunscreens containing antioxidants is considered. The aim of this study was to evaluate the cutaneous penetration of most marketed UV-filters combined with trans-resveratrol (RES) and beta-carotene (BTC) since few studies report skin penetration when such compounds are applied. Formulations containing octocrylene, octyl methoxycinnamate, avobenzone and bemotrizinole were prepared and supplemented or not with BTC, or with RES, or with both compounds in combination. Penetration studies were performed using Franz vertical diffusion cells and porcine ear skin as the biological membrane. The quantification of UV-filters and antioxidants in the stratum corneum (SC), viable epidermis plus dermis and receptor fluid was performed by HPLC. Results suggested that UV-filters and antioxidants did not permeate the skin but were retained for 12h post application. About 90% and 80%, respectively, of the total penetrated amount of UV-filters and antioxidants was found in the SC. Interestingly, it was observed that BTC, alone or combined with RES, reduced the skin retention of UV-filters on average by 63%. In conclusion, this study demonstrated that the combination of antioxidants and UV-filters in sunscreens is advantageous for cutaneous penetration, since BTC and BTC+RES improved sunscreen safety by reducing delivery of the four UV-filters in the study into SC and viable epidermis. Copyright © 2015 Elsevier B.V. All rights reserved.

Enhanced skin permeation of naltrexone by pulsed electromagnetic fields in human skin in vitro.

PubMed

Krishnan, Gayathri; Edwards, Jeffrey; Chen, Yan; Benson, Heather A E

2010-06-01

The aim of the present study was to evaluate the skin permeation of naltrexone (NTX) under the influence of a pulsed electromagnetic field (PEMF). The permeation of NTX across human epidermis and a silicone membrane in vitro was monitored during and after application of the PEMF and compared to passive application. Enhancement ratios of NTX human epidermis permeation by PEMF over passive diffusion, calculated based on the AUC of cumulative NTX permeation to the receptor compartment verses time for 0-4 h, 4-8 h, and over the entire experiment (0-8 h) were 6.52, 5.25, and 5.66, respectively. Observation of the curve indicated an initial enhancement of NTX permeation compared to passive delivery whilst the PEMF was active (0-4 h). This was followed by a secondary phase after termination of PEMF energy (4-8 h) in which there was a steady increase in NTX permeation. No significant enhancement of NTX penetration across silicone membrane occurred with PEMF application in comparison to passively applied NTX. In a preliminary experiment PEMF enhanced the penetration of 10 nm gold nanoparticles through the stratum corneum as visualized by multiphoton microscopy. This suggests that the channels through which the nanoparticles move must be larger than the 10 nm diameter of these rigid particles. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association

Topical delivery of roxithromycin solid-state forms entrapped in vesicles.

PubMed

Csongradi, Candice; du Plessis, Jeanetta; Aucamp, Marique Elizabeth; Gerber, Minja

2017-05-01

Recently, considerable interest developed in using newer/improved antibiotics for the treatment of Acne vulgaris. During this study, different roxithromycin solid-state forms (i.e. crystalline and amorphous) were encapsulated into vesicle systems (niosomes, proniosomes, ufosomes and pro-ufosomes) for dermis targeted delivery. Characterization of the vesicles was done with transmission electron microscopy, light microscopy, droplet size, droplet size distribution, pH, zeta-potential and entrapment efficiency percentage. Finally, comparative release and topical diffusion studies were performed, to evaluate if targeted topical delivery was obtained and if the roxithromycin solid-state amorphous forms resulted in improved topical delivery. Vesicle systems containing different roxithromycin (2%) solid-state forms were successfully prepared and characterized. The vesicles showed optimal properties for topical delivery. All carrier systems had topical delivery to the epidermis-dermis, whilst no roxithromycin was found in the receptor compartment or stratum corneum-epidermis. The niosomes were the leading formulation and the two amorphous forms had better topical delivery than the crystalline form. Successful targeted delivery of roxithromycin was obtained in the dermis, where the activity against Propionibacterium acnes is needed. The amorphous forms seemed to have held their solid-state form during formulation and in the vesicles, showing improved topical delivery in comparison to the crystalline form. Copyright © 2017 Elsevier B.V. All rights reserved.

The Permeability Enhancing Mechanism of DMSO in Ceramide Bilayers Simulated by Molecular Dynamics

PubMed Central

Notman, Rebecca; den Otter, Wouter K.; Noro, Massimo G.; Briels, W. J.; Anwar, Jamshed

2007-01-01

The lipids of the topmost layer of the skin, the stratum corneum, represent the primary barrier to molecules penetrating the skin. One approach to overcoming this barrier for the purpose of delivery of active molecules into or via the skin is to employ chemical permeability enhancers, such as dimethylsulfoxide (DMSO). How these molecules exert their effect at the molecular level is not understood. We have investigated the interaction of DMSO with gel-phase bilayers of ceramide 2, the predominant lipid in the stratum corneum, by means of molecular dynamics simulations. The simulations satisfactorily reproduce the phase behavior and the known structural parameters of ceramide 2 bilayers in water. The effect of DMSO on the gel-phase bilayers was investigated at various concentrations over the range 0.0−0.6 mol fraction DMSO. The DMSO molecules accumulate in the headgroup region and weaken the lateral forces between the ceramides. At high concentrations of DMSO (≥0.4 mol fraction), the ceramide bilayers undergo a phase transition from the gel phase to the liquid crystalline phase. The liquid-crystalline phase of ceramides is expected to be markedly more permeable to solutes than the gel phase. The results are consistent with the experimental evidence that high concentrations of DMSO fluidize the stratum corneum lipids and enhance permeability. PMID:17513383

An evaluation of the skin stripping of wound dressing adhesives.

PubMed

Waring, M; Bielfeldt, S; Mätzold, K; Wilhelm, K P; Butcher, M

2011-09-01

This study looks at six different modern wound dressings to investigate how likely they are to cause skin stripping and impairment of the skin's barrier function. Healthy volunteers had each dressing applied, removed and reapplied to the skin on their back over the study period of 15 days. Skin barrier function was investigated using the amount of transepidermal water loss (TEWL) and then related to the amount of skin stripping, investigated by measuring stained skin removal, the thickness of the stratum corneum after treatment, and the amount of skin attached to the removed dressings. General signs of trauma, such as skin dryness and erythema, were investigated by subjective and objective parameters. TEWL values measured on the untreated test area, as well as after application of Urgotul Trio, remained relatively unchanged and Mepilex Border decreased slightly (?1g/m2/h), while all other dressings displayed an increased in TEWL: Allevyn Adhesive (5g/m2/h), Versiva XC (14g/m2/h), Comfeel Plus (22g/m2/h) and Biatain (28g/m2/h). By the end of the study, only the untreated area (mean 43% dye remaining), Mepilex Border (76%) and Urgotul Trio (34%) areas had visible dye remaining. It is interesting to note that the untreated site had a colour change, suggesting loss of stratum corneum, due to the shedding of skin cells from the surface. The increase in total skin colour for Comfeel Plus and Biatain after day 8 might be assigned to an increased redness due to erythema. All the dressings showed evidence of stratum corneum attached to the adhesive, except Mepilex Border, which appeared to be free of any attached stratum corneum. Overall the best performance in terms of skin protection and failure to cause skin trauma was found to be for Mepilex Border. This project was funded by a grant from Mölnlycke Healthcare Ltd.

Improving diaper design to address incontinence associated dermatitis

PubMed Central

2010-01-01

Background Incontinence associated dermatitis (IAD) is an inflammatory skin disease mainly triggered by prolonged skin contact with urine, feces but also liberal detergent use when cleansing the skin. To minimize the epidermal barrier challenge we optimized the design of adult incontinence briefs. In the fluid absorption area we interposed a special type of acidic, curled-type of cellulose between the top sheet in contact with the skin and the absorption core beneath containing the polyacrylate superabsorber. The intention was to minimize disturbance of the already weak acid mantle of aged skin. We also employed air-permeable side panels to minimize skin occlusion and swelling of the stratum corneum. Methods The surface pH of diapers was measured after repeated wetting with a urine substitute fluid at the level of the top sheet. Occlusive effects and hydration of the stratum corneum were measured after a 4 hour application of different side panel materials by corneometry on human volunteers. Finally, we evaluated skin symptoms in 12 patients with preexisting IAD for 21 days following the institutional switch to the optimized diaper design. Local skin care protocols remained in place unchanged. Results The improved design created a surface pH of 4.6 which was stable even after repeated wetting throughout a 5 hour period. The "standard design" briefs had values of 7.1, which is alkaline compared to the acidic surface of normal skin. Side panels made from non-woven material with an air-permeability of more than 1200 l/m2/s avoided excessive hydration of the stratum corneum when compared to the commonly employed air-impermeable plastic films. Resolution of pre-existing IAD skin lesions was noted in 8 out of 12 patients after the switch to the optimized brief design. Conclusions An improved design of adult-type briefs can create an acidic pH on the surface and breathable side panels avoid over-hydration of the stratum corneum and occlusion. This may support the

Reconstructed human epidermis: A model to study the barrier function

NASA Astrophysics Data System (ADS)

Barbotteau, Y.; Gontier, E.; Barberet, P.; Cappadoro, M.; De Wever, B.; Habchi, C.; Incerti, S.; Mavon, A.; Moretto, P.; Pouthier, T.; Smith, R. W.; Ynsa, M. D.

2005-04-01

The use of in vitro reconstructed human epidermis (RHE) by the cosmetic and pharmaceutical industries is increasing because of its similar physiological mechanisms to native human skin. With the advent of ethic laws on animal experimentation, RHE provides an helpful alternative for the test of formulations. The aim of this study is to check that the RHE mineral status is comparable to that of human native skin by investigating the elemental distributions in the epidermis strata. In addition, possible deleterious effects of the transport on the epidermis ionic content were studied by nuclear microscopy.

Cytologic features of hyperplastic epidermis.

PubMed

Eng, A M; Worobec, S

1977-10-01

The cytologic features of hyperplastic epidermis in common lesions such as verruca, seborrheic keratosis, condyloma accuminatum, fibroepithelial polyp, corn, radiodermatitis, prurigo nodularis, epidermal nevus, dermatofibroma, tricholemmona, inverted follicular keratosis and pseudoepitheliomatous hyperplasia were studied. Common, as well as distinguishing cytologic points are recognized.

Sarcoptic mange in free-ranging raccoon dogs (Nyctereutes procyonoides) in Japan.

PubMed

Ninomiya, Hiroyoshi; Ogata, Munetsugu

2005-06-01

Sarcoptes scabiei infestation was diagnosed in three freshly dead free-ranging raccoon dogs (Nyctereutes procyonoides) in Kanagawa Prefecture, Japan. The dogs presented with an alopecic pruritic skin disease, with signs of alopecia on the ears, muzzle, around the eyes, elbow, thigh and the neck, and hyperpigmented and crusted skin lesions, which had a severe malodour. Skin scrapings revealed the presence of the mite Sarcoptes scabiei. Histopathology of lesions demonstrated marked acanthosis, hyperkeratosis, parakeratosis and fungal elements, which were subsequently identified as Acremonium sp., Alternaria sp. and an unknown fungus. Mite segments were located mainly in the stratum corneum and also in the stratum granulosum. Tunnels could be observed in the hyperkeratotic stratum corneum. Scanning electron microscopy (SEM) revealed the tortoise-like Sarcoptes scabiei with four long bristles, suckers and blade-like claws on legs 1 and 2, cuticular spines, prominent body striations and a terminal anus. SEM also revealed an adult female mite digging a tunnel with the head wedged into the very end of the closed burrow. Tunnels filled with eggshells, corneocyte debris and faecal pellets were also observed.

Estrogen modulates mesenchyme-epidermis interactions in the adult nipple

PubMed Central

Wu, Hsing-Jung; Oh, Ji Won; Spandau, Dan F.; Tholpady, Sunil; Diaz, Jesus; Schroeder, Laura J.; Offutt, Carlos D.; Glick, Adam B.; Plikus, Maksim V.; Koyama, Sachiko

2017-01-01

Maintenance of specialized epidermis requires signals from the underlying mesenchyme; however, the specific pathways involved remain to be identified. By recombining cells from the ventral skin of the K14-PTHrP transgenic mice [which overexpress parathyroid hormone-related protein (PTHrP) in their developing epidermis and mammary glands] with those from wild type, we show that transgenic stroma is sufficient to reprogram wild-type keratinocytes into nipple-like epidermis. To identify candidate nipple-specific signaling factors, we compared gene expression signatures of sorted Pdgfrα-positive ventral K14-PTHrP and wild-type fibroblasts, identifying differentially expressed transcripts that are involved in WNT, HGF, TGFβ, IGF, BMP, FGF and estrogen signaling. Considering that some of the growth factor pathways are targets for estrogen regulation, we examined the upstream role of this hormone in maintaining the nipple. Ablation of estrogen signaling through ovariectomy produced nipples with abnormally thin epidermis, and we identified TGFβ as a negatively regulated target of estrogen signaling. Estrogen treatment represses Tgfβ1 at the transcript and protein levels in K14-PTHrP fibroblasts in vitro, while ovariectomy increases Tgfb1 levels in K14-PTHrP ventral skin. Moreover, ectopic delivery of Tgfβ1 protein into nipple connective tissue reduced epidermal proliferation. Taken together, these results show that specialized nipple epidermis is maintained by estrogen-induced repression of TGFβ signaling in the local fibroblasts. PMID:28289136

Surfactant sodium lauryl sulfate enhances skin vaccination: molecular characterization via a novel technique using ultrafiltration capillaries and mass spectrometric proteomics.

PubMed

Huang, Chun-Ming; Wang, Chao-Cheng; Kawai, Mikako; Barnes, Stephen; Elmets, Craig A

2006-03-01

The skin is a highly accessible organ and thus provides an attractive immune environment for cost-effective, simple, and needle-free delivery of vaccines and immunomodulators. In this study, we pretreated mouse skin with an anionic surfactant, sodium lauryl sulfate (SLS), for a short period of time (10 min) followed by epicutaneous vaccination with hen egg lysozyme antigen. We demonstrated for the first time that pretreatment of skin with surfactant SLS significantly enhances the production of antibody to hen egg lysozyme. Short term pretreatment with SLS disorganized the stratum corneum, extracted partial lamellar lipids, induced the maturation of Langerhans cells, and did not result in epidermis thickening. To reveal the mechanism underlying these changes, particularly at the molecular level, we used a novel proteomic technique using ultrafiltration capillaries and mass spectrometry to identify in vivo proteins/peptides secreted in the SLS-pretreated skin. Two secretory proteins, named as calcium-binding protein S100A9 and thymosin beta4, were identified by this novel technique. These two proteins thus may provide new insight into the enhancing effect of surfactants on skin vaccination.

Linkage of autosomal recessive lamellar ichthyosis to chromosome 14q

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russell, L.J.; Compton, J.G.; Bale, S.J.

The authors have mapped the locus for lamellar ichthyosis (LI), an autosomal recessive skin disease characterized by abnormal cornification of the epidermis. Analysis using both inbred and outbred families manifesting severe LI showed complete linkage to several markers within a 9.3-cM region on chromosome 14q11. Affected individuals in inbred families were also found to have striking homozygosity for markers in this region. Linkage-based genetic counseling and prenatal diagnosis is now available for informative at-risk families. Several transcribed genes have been mapped to the chromosome 14 region containing the LI gene. The transglutaminase 1 gene (TGM1), which encodes one of themore » enzymes responsible for cross-linking epidermal proteins during formation of the stratum corneum, maps to this interval. The TGM1 locus was completely linked to LI (Z = 9.11), suggesting that TGM1 is a good candidate for further investigation of this disorder. The genes for four serine proteases also map to this region but are expressed only in hematopoietic or mast cells, making them less likely candidates.« less

Microneedle-based drug delivery systems for transdermal route.

PubMed

Pierre, Maria Bernadete Riemma; Rossetti, Fabia Cristina

2014-03-01

Transdermal delivery offers an attractive, noninvasive administration route but it is limited by the skin's barrier to penetration. Minimally invasive techniques, such as the use of microneedles (MNs), bypass the stratum corneum (SC) barrier to permit the drug's direct access to the viable epidermis. These novel micro devices have been developed to puncture the skin for the transdermal delivery of hydrophilic drugs and macromolecules, including peptides, DNA and other molecules, that would otherwise have difficulty passing the outermost layer of the skin, the SC. Using the tools of the microelectronics industry, MNs have been fabricated with a range of sizes, shapes and materials. MNs have been shown to be robust enough to penetrate the skin and dramatically increase the skin permeability of several drugs. Moreover, MNs have reduced needle insertion pain and tissue trauma and provided controlled delivery across the skin. This review focuses on the current state of the art in the transdermal delivery of drugs using various types of MNs and developments in the field of microscale devices, as well as examples of their uses and clinical safety.

Penetration of Ufenamate into Intact, Stripped, or Delipidized Skin Using Different Vehicles.

PubMed

Iino, Hayato; Fujii, Makiko; Fujino, Manami; Koizumi, Naoya; Watanabe, Yoshiteru

2015-01-01

The purpose of this study was to clarify the effect of skin condition on skin penetration of the very high lipophilic drug, ufenamate (UF). UF was applied to stripped or delipidized skin using liquid paraffin (LP) or purified water containing polysorbate 80 at a dose of 2 µL/cm(2). We found that UF penetration into intact and stripped skin using a water vehicle was respectively 5 and 10 times higher than that using LP. UF is freely soluble in oil and insoluble in water; thus, activity in water is higher than that in LP. Therefore, it is useful to use a water-based vehicle for both intact sites and those with defective stratum corneum (SC). Conversely, we found that delipidization of SC decreased the penetration of UF significantly with both LP and water, and the amount measured in the epidermis was 1 µg/cm(2) with both vehicles. This indicates that UF is not suitable for so-called "dry skin." This study revealed clinically relevant differences in the penetration of UF into intact, stripped, or delipidized skin conditions.

Magnetophoresis for enhancing transdermal drug delivery: Mechanistic studies and patch design

PubMed Central

Murthy, S. Narasimha; Sammeta, Srinivasa M.; Bower, C.

2017-01-01

Magnetophoresis is a method of enhancement of drug permeation across the biological barriers by application of magnetic field. The present study investigated the mechanistic aspects of magnetophoretic transdermal drug delivery and also assessed the feasibility of designing a magnetophoretic transdermal patch system for the delivery of lidocaine. In vitro drug permeation studies were carried out across the porcine epidermis at different magnetic field strengths. The magnetophoretic drug permeation “flux enhancement factor” was found to increase with the applied magnetic field strength. The mechanistic studies revealed that the magnetic field applied in this study did not modulate permeability of the stratum corneum barrier. The predominant mechanism responsible for magnetically mediated drug permeation enhancement was found to be “magnetokinesis”. The octanol/water partition coefficient of drugs was also found to increase when exposed to the magnetic field. A reservoir type transdermal patch system with a magnetic backing was designed for in vivo studies. The dermal bioavailability (AUC0–6 h) from the magnetophoretic patch system in vivo, in rats was significantly higher than the similarly designed nonmagnetic control patch. PMID:20728484

[Skin hydration and hydrating products].

PubMed

Duplan, H; Nocera, T

2018-05-01

One of the skin's principal functions is to protect the body against its environment by maintaining an effective epidermal barrier, not only against external factors, but also to prevent water loss from the body. Indeed, water homeostasis is vital for the normal physiological functioning of skin. Hydration levels affect not only visible microscopic parameters such as the suppleness and softness of skin, but also molecular parameters, enzyme activities and cellular signalling within the epidermis. The body is continually losing some of its water, but this phenomenon is limited and the optimal hydration gradient in skin is ensured via a set of sophisticated regulatory processes that rely on the functional and dynamic properties of the uppermost level of the skin consisting of the stratum corneum. The present article brings together data recently acquired in the fields of skin hydration and the characterisation of dehydrated or dry skin, whether through study of the regulatory processes involved or as a result of changes in the techniques used for in situ measurement, and thus in optimisation of management. Copyright © 2018. Published by Elsevier Masson SAS.

Measurement, analysis and prediction of topical UV filter bioavailability.

PubMed

Roussel, L; Gilbert, E; Salmon, D; Serre, C; Gabard, B; Haftek, M; Maibach, H I; Pirot, F

2015-01-30

The aim of the present study was to objectively quantify and predict bioavailability of three sunscreen agents (i.e., benzophenone-3, 2-ethylhexylsalicylate, and 2 ethylhexyl-4-methoxycinnamate) in epidermis treated by petrolatum and emulsion-based formulations for 7 and 30min on four human volunteers. Profiles of sunscreen agents through stratum corneum (SC), derived from the assessment of chemical amounts in SC layers collected by successive adhesive tape-stripping, were successfully fitted to Fick's second law of diffusion. Therefore, permeability coefficients of sunscreen agents were found lower with petrolatum than with emulsion based formulations confirming the crucial role of vehicle in topical delivery. Furthermore, the robustness of that methodology was confirmed by the linear relationship between the chemical absorption measured after 30min and that predicted from the 7-min exposure experiment. Interestingly, in this dermatopharmacokinetic method, the deconvolution of permeability coefficients in their respective partition coefficients and absorption constants allowed a better understanding of vehicle effects upon topical bioavailability mechanisms and bioequivalence of skin products. Copyright © 2014 Elsevier B.V. All rights reserved.

A Case of Inflammatory Generalized Type of Peeling Skin Syndrome Possibly Caused by a Homozygous Missense Mutation of CDSN

PubMed Central

Kawakami, Hiroshi; Uchiyama, Masaki; Maeda, Tatsuo; Tsunoda, Takahiko; Mitsuhashi, Yoshihiko; Tsuboi, Ryoji

2014-01-01

A 54-year-old Japanese woman had repetitive superficial skin peeling and ensuing erythematous changes in the sites since infancy. Her parents had a consanguineous marriage, and she was the only individual affected in her family tree. The erythematous changes seemed to worsen in the summer. Histologically, hyperkeratosis and splitting of the epidermis within the stratum corneum was noted, and electron microscopy revealed shedding of corneal cells in the horny layer and normal-looking corneodesmosomes. Gene analysis revealed a homozygous missense mutation at c.1358G>A in CDSN. Electron microscopic examination of the length and number of corneodesmosomes revealed statistically significant shortness and sparsity in the affected individual (mean ± SD 386.2 ± 149.5 nm) compared with that of an age- and site-matched control (406.6 ± 182.3 nm). We speculate that this size shrinkage of corneodesmosomes might be the result of a missense mutation of CDSN and that this could be one of the factors contributing to the pathological process of skin peeling. PMID:25473393

A Case of Inflammatory Generalized Type of Peeling Skin Syndrome Possibly Caused by a Homozygous Missense Mutation of CDSN.

PubMed

Kawakami, Hiroshi; Uchiyama, Masaki; Maeda, Tatsuo; Tsunoda, Takahiko; Mitsuhashi, Yoshihiko; Tsuboi, Ryoji

2014-09-01

A 54-year-old Japanese woman had repetitive superficial skin peeling and ensuing erythematous changes in the sites since infancy. Her parents had a consanguineous marriage, and she was the only individual affected in her family tree. The erythematous changes seemed to worsen in the summer. Histologically, hyperkeratosis and splitting of the epidermis within the stratum corneum was noted, and electron microscopy revealed shedding of corneal cells in the horny layer and normal-looking corneodesmosomes. Gene analysis revealed a homozygous missense mutation at c.1358G>A in CDSN. Electron microscopic examination of the length and number of corneodesmosomes revealed statistically significant shortness and sparsity in the affected individual (mean ± SD 386.2 ± 149.5 nm) compared with that of an age- and site-matched control (406.6 ± 182.3 nm). We speculate that this size shrinkage of corneodesmosomes might be the result of a missense mutation of CDSN and that this could be one of the factors contributing to the pathological process of skin peeling.

Absorption spectra and light penetration depth of normal and pathologically altered human skin

NASA Astrophysics Data System (ADS)

Barun, V. V.; Ivanov, A. P.; Volotovskaya, A. V.; Ulashchik, V. S.

2007-05-01

A three-layered skin model (stratum corneum, epidermis, and dermis) and engineering formulas for radiative transfer theory are used to study absorption spectra and light penetration depths of normal and pathologically altered skin. The formulas include small-angle and asymptotic approximations and a layer-addition method. These characteristics are calculated for wavelengths used for low-intensity laser therapy. We examined several pathologies such as vitiligo, edema, erythematosus lupus, and subcutaneous wound, for which the bulk concentrations of melanin and blood vessels or tissue structure (for subcutaneous wound) change compared with normal skin. The penetration depth spectrum is very similar to the inverted blood absorption spectrum. In other words, the depth is minimal at blood absorption maxima. The calculated absorption spectra enable the power and irradiation wavelength providing the required light effect to be selected. Relationships between the penetration depth and the diffuse reflectance coefficient of skin (unambiguously expressed through the absorption coefficient) are analyzed at different wavelengths. This makes it possible to find relationships between the light fields inside and outside the tissue.

Molecular Characterization of Squamous Cell Carcinomas From Recessive Dystrophic Epidermolysis Bullosa

DTIC Science & Technology

2006-09-01

junctions found primarily in epithelial tissues but also in certain non-epithelial tissues including the meninges, dendritic reticular cells of lymph node...epidermal thickening, a phenotype becoming more prominent in adult animals. To further examine the transition between the stratum granulosum and stratum...granular cell layers of wild-type and transgenic skin. In control epidermis, an abrupt transition was observed from the granular layer to the stratum

Human epidermis is a novel site of phospholipase B expression.

PubMed

Maury, Eric; Prévost, Marie Claude; Nauze, Michel; Redoulès, Daniel; Tarroux, Roger; Charvéron, Marie; Salles, Jean Pierre; Perret, Bertrand; Chap, Hugues; Gassama-Diagne, Ama

2002-07-12

Phospholipase B (PLB) is an enzyme that displays both phospholipase A(2) and lysophospholipase activities. Analysis of human epidermis homogenates indicated the presence of a 97 kDa PLB protein, as well as a phospholipase A(2) activity, both being enriched in the soluble fraction. Immunolabelling and in situ hybridization experiments showed that this enzyme is expressed in the different layers of epidermis with an accumulation at the dermo-epidermis junction. RT-PCR data indicated that PLB is specifically expressed in natural and reconstructed epidermis. By 3'-RACE-PCR and screening of human genome databases, we obtained a 3600 bp cDNA coding for human PLB highly homologous to already described intestinal brush border PLBs. These data led us to conclude that the soluble PLB corresponds to a proteolytic cleavage of the membrane anchored protein. Altogether, our results provide the first characterization of human PLB which should play an important role in epidermal barrier function.

On the importance of body posture and skin modelling with respect to in situ electric field strengths in magnetic field exposure scenarios

NASA Astrophysics Data System (ADS)

Schmid, Gernot; Hirtl, Rene

2016-06-01

The reference levels and maximum permissible exposure values for magnetic fields that are currently used have been derived from basic restrictions under the assumption of upright standing body models in a standard posture, i.e. with arms laterally down and without contact with metallic objects. Moreover, if anatomical modelling of the body was used at all, the skin was represented as a single homogeneous tissue layer. In the present paper we addressed the possible impacts of posture and skin modelling in scenarios of exposure to a 50 Hz uniform magnetic field on the in situ electric field strength in peripheral tissues, which must be limited in order to avoid peripheral nerve stimulation. We considered different body postures including situations where body parts form large induction loops (e.g. clasped hands) with skin-to-skin and skin-to-metal contact spots and compared the results obtained with a homogeneous single-layer skin model to results obtained with a more realistic two-layer skin representation consisting of a low-conductivity stratum corneum layer on top of a combined layer for the cellular epidermis and dermis. Our results clearly indicated that postures with loops formed of body parts may lead to substantially higher maximum values of induced in situ electric field strengths than in the case of standard postures due to a highly concentrated current density and in situ electric field strength in the skin-to-skin and skin-to-metal contact regions. With a homogeneous single-layer skin, as is used for even the most recent anatomical body models in exposure assessment, the in situ electric field strength may exceed the basic restrictions in such situations, even when the reference levels and maximum permissible exposure values are not exceeded. However, when using the more realistic two-layer skin model the obtained in situ electric field strengths were substantially lower and no violations of the basic restrictions occurred, which can be explained by the

Skin penetration and antioxidant effect of cosmeto-textiles with gallic acid.

PubMed

Alonso, C; Martí, M; Barba, C; Lis, M; Rubio, L; Coderch, L

2016-03-01

In this work, the antioxidant gallic acid (GA) has been encapsulated in microspheres prepared with poly-ε-caprolactone (PCL) and incorporated into polyamide (PA) obtaining the cosmeto-textile. The topical application of the cosmeto-textile provides a reservoir effect in the skin delivery of GA. The close contact of the cosmeto-textile, containing microsphere-encapsulated GA (ME-GA), with the skin and their corresponding occlusion, may be the main reasons that explain the crossing of active principle (GA) through the skin barrier, located in the stratum corneum, and its penetration into the different compartments of the skin, epidermis and dermis. An ex vivo assessment was performed to evaluate the antioxidant effect of the ME-GA on the stratum corneum (SC) using the thiobarbituric acid-reactive species (TBARS) test. The test is based on a non-invasive ex vivo methodology that evaluates lipid peroxides formed in the outermost layers of the SC from human volunteers after UV radiation to determine the effectiveness of an antioxidant. In this case, a ME-GA cosmeto-textile or ME-GA formulation were applied to the skin in vivo and lipid peroxidation (LPO) in the horny layer were determined after UV irradiation. This methodology may be used as a quality control tool to determine ex vivo the percentage of LPO inhibition on human SC for a variety of antioxidants that are topically applied, in this case GA. Results show that LPO formation was inhibited in human SC when GA was applied directly or embedded in the cosmeto-textile, demonstrating the effectiveness of both applications. The percentage of LPO inhibition obtained after both topical applications was approximately 10% for the cosmeto-textile and 41% for the direct application of microspheres containing GA. This methodology could be used to determine the effectiveness of topically applied antioxidants encapsulated in cosmeto-textiles on human SC. Copyright © 2016 Elsevier B.V. All rights reserved.

Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery

PubMed Central

Szunerits, Sabine; Boukherroub, Rabah

2018-01-01

Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs), which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum, the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section “Frontiers in Bioengineering and Biotechnology,” the advances in this field and the handful of

Leaf Epidermis of the Rheophyte Dyckia brevifolia Baker (Bromeliaceae)

PubMed Central

Lobo, Ghislaine Maria; de Souza, Thaysi Ventura; Voltolini, Caroline Heinig; Reis, Ademir

2013-01-01

Some species of Dyckia Schult. f., including Dyckia brevifolia Baker, are rheophytes that live in the fast-moving water currents of streams and rivers which are subject to frequent flooding, but also period of low water. This study aimed to analyze the leaf epidermis of D. brevifolia in the context of epidermal adaptation to this aquatic plant's rheophytic habitat. The epidermis is uniseriate, and the cuticle is thickened. The inner periclinal and anticlinal walls of the epidermal cells are thickened and lignified. Stomata are tetracytic, located in the depressions in relation to the surrounding epidermal cells, and covered by peltate trichomes. While the epidermal characteristics of D. brevifolia are similar to those of Bromeliaceae species, this species has made particular adaptations of leaf epidermis in response to its rheophytic environment. PMID:23864825

Antifungal Effect of Non-Woven Textiles Containing Polyhexamethylene Biguanide with Sophorolipid: A Potential Method for Tinea Pedis Prevention

PubMed Central

Sanada, Hiromi; Nakagami, Gojiro; Takehara, Kimie; Goto, Taichi; Ishii, Nanase; Yoshida, Satoshi; Ryu, Mizuyuki; Tsunemi, Yuichiro

2014-01-01

Tinea pedis is a preventable skin disease common in elderly or diabetic patients. Daily foot washing is effective for prevention, but can be difficult for many patients. Additionally, conventional methods cannot eliminate fungi within the stratum corneum, a common site for fungal invasion. This study investigates the antifungal effects, cytotoxicity, permeability, and efficacy of non-woven textiles containing polyhexamethylene biguanide (PHMB) mixed with sophorolipid. Permeability of PHMB with varying concentrations of sophorolipid was assessed via a cultured skin model. Stratum corneum PHMB concentration was quantified by polyvinylsulphuric acid potassium salt titration and cytotoxicity was assayed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Antifungal effects were evaluated via a new cultured skin/Trichophyton mentagrophytes model, with varying PHMB exposure duration. Clinically-isolated Trichophyton were applied to the feet of four healthy volunteers and then immediately treated with the following methods: washing with soap, a non-woven textile with PHMB, the textile without PHMB, or without washing. Fungal colony forming units (CFUs) were evaluated after one of these treatments were performed. Sophorolipid with various concentrations significantly facilitated PHMB permeation into the stratum corneum, which was not in a dose-dependent manner. Significant PHMB antifungal effects were achieved at 30 min, with low cytotoxicity. Textiles containing PHMB significantly reduced CFU of fungi in healthy volunteers to levels comparable to soap washing. Our results indicate the utility of this product for tinea pedis prevention in clinical settings. PMID:27429269

Antifungal Effect of Non-Woven Textiles Containing Polyhexamethylene Biguanide with Sophorolipid: A Potential Method for Tinea Pedis Prevention.

PubMed

Sanada, Hiromi; Nakagami, Gojiro; Takehara, Kimie; Goto, Taichi; Ishii, Nanase; Yoshida, Satoshi; Ryu, Mizuyuki; Tsunemi, Yuichiro

2014-04-08

Tinea pedis is a preventable skin disease common in elderly or diabetic patients. Daily foot washing is effective for prevention, but can be difficult for many patients. Additionally, conventional methods cannot eliminate fungi within the stratum corneum, a common site for fungal invasion. This study investigates the antifungal effects, cytotoxicity, permeability, and efficacy of non-woven textiles containing polyhexamethylene biguanide (PHMB) mixed with sophorolipid. Permeability of PHMB with varying concentrations of sophorolipid was assessed via a cultured skin model. Stratum corneum PHMB concentration was quantified by polyvinylsulphuric acid potassium salt titration and cytotoxicity was assayed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Antifungal effects were evaluated via a new cultured skin/Trichophyton mentagrophytes model, with varying PHMB exposure duration. Clinically-isolated Trichophyton were applied to the feet of four healthy volunteers and then immediately treated with the following methods: washing with soap, a non-woven textile with PHMB, the textile without PHMB, or without washing. Fungal colony forming units (CFUs) were evaluated after one of these treatments were performed. Sophorolipid with various concentrations significantly facilitated PHMB permeation into the stratum corneum, which was not in a dose-dependent manner. Significant PHMB antifungal effects were achieved at 30 min, with low cytotoxicity. Textiles containing PHMB significantly reduced CFU of fungi in healthy volunteers to levels comparable to soap washing. Our results indicate the utility of this product for tinea pedis prevention in clinical settings.

Genetics Home Reference: Netherton syndrome

MedlinePlus

... stratum corneum. LEKT1 is also involved in normal hair growth, the development of lymphocytes in the thymus, and ... Loss of LEKT1 function also results in abnormal hair growth and immune dysfunction that leads to allergies, asthma, ...

Nuclear microprobe investigation of the penetration of ultrafine zinc oxide into intact and tape-stripped human skin

NASA Astrophysics Data System (ADS)

Szikszai, Z.; Kertész, Zs.; Bodnár, E.; Major, I.; Borbíró, I.; Kiss, Á. Z.; Hunyadi, J.

2010-06-01

Ultrafine metal oxides, such as titanium dioxide and zinc oxide are widely used in cosmetic and health products like sunscreens. These oxides are potent UV filters and the small particle size makes the product more transparent compared to formulations containing coarser particles. In the present work the penetration of ultrafine zinc oxide into intact and tape-stripped human skin was investigated using nuclear microprobe techniques, such as proton induced X-ray spectroscopy and scanning transmission ion microscopy. Our results indicate that the penetration of ultrafine zinc oxide, in a hydrophobic basis gel with 48 h application time, is limited to the stratum corneum layer of the intact skin. Removing the stratum corneum partially or entirely by tape-stripping did not cause the penetration of the particles into the deeper dermal layers; the zinc particles remained on the surface of the skin.

Management of Patients with Atopic Dermatitis: The Role of Emollient Therapy

PubMed Central

Catherine Mack Correa, M.; Nebus, Judith

2012-01-01

Atopic dermatitis is a common inflammatory skin disorder that afflicts a growing number of young children. Genetic, immune, and environmental factors interact in a complex fashion to contribute to disease expression. The compromised stratum corneum found in atopic dermatitis leads to skin barrier dysfunction, which results in aggravation of symptoms by aeroallergens, microbes, and other insults. Infants—whose immune system and epidermal barrier are still developing—display a higher frequency of atopic dermatitis. Management of patients with atopic dermatitis includes maintaining optimal skin care, avoiding allergic triggers, and routinely using emollients to maintain a hydrated stratum corneum and to improve barrier function. Flares of atopic dermatitis are often managed with courses of topical corticosteroids or calcineurin inhibitors. This paper discusses the role of emollients in the management of atopic dermatitis, with particular emphasis on infants and young children. PMID:23008699

Estimation of within-stratum variance for sample allocation: Foreign commodity production forecasting

NASA Technical Reports Server (NTRS)

Chhikara, R. S.; Perry, C. R., Jr. (Principal Investigator)

1980-01-01

The problem of determining the stratum variances required for an optimum sample allocation for remotely sensed crop surveys is investigated with emphasis on an approach based on the concept of stratum variance as a function of the sampling unit size. A methodology using the existing and easily available information of historical statistics is developed for obtaining initial estimates of stratum variances. The procedure is applied to variance for wheat in the U.S. Great Plains and is evaluated based on the numerical results obtained. It is shown that the proposed technique is viable and performs satisfactorily with the use of a conservative value (smaller than the expected value) for the field size and with the use of crop statistics from the small political division level.

Effects of soap and detergents on skin surface pH, stratum corneum hydration and fat content in infants.

PubMed

Gfatter, R; Hackl, P; Braun, F

1997-01-01

In adults the influence of cleansing preparations on the pH, fat content and hydration of the skin is well documented. Studies in newborn and small infants have not been reported. Our study aimed at examining whether similar effects can be ascertained in infants. Infants without skin disease, aged 2 weeks to 16 months, entered an open, controlled and randomized study. Ten infants each had skin washed with tap water (control group), liquid detergent (pH 5.5), compact detergent (pH 5.5) or alkaline soap (pH 9.5). The pH, fat content and hydration were measured before and 10 min after cleansing. Findings were statistically evaluated by parametric covariance analysis. The skin pH increased from an average of 6.60 after cleansing in all groups. The smallest increase (+0.19) was observed in the control group, the largest (+0.45) after washing with alkaline soap. After treatment with liquid or compact detergent, the increase of the pH was only 0.09 higher than for the control group. In comparison to the compact and liquid detergents, the alkaline soap group had a significantly higher increase in pH. The fat content (mean starting value: 4.34 micrograms/cm2) decreased after washing in all groups; the smallest effect was observed in the control group (decrease of 0.93 micrograms/cm2), the highest for the alkaline soap group (decrease of 4.81 micrograms/cm2). In comparison to the compact and liquid detergents, the alkaline soap group had a higher decrease in fat content. This difference was significant for compact detergents. No statistically significant differences were observed for hydration before versus after washing. Each cleansing agent, even normal tap water, influences the skin surface. The increase of the skin pH irritates the physiological protective 'acid mantle', changes the composition of the cutaneous bacterial flora and the activity of enzymes in the upper epidermis, which have an acid pH optimum. The dissolution of fat from the skin surface may influence the

Electrochemical monitoring of native catalase activity in skin using skin covered oxygen electrode.

PubMed

Nocchi, Sarah; Björklund, Sebastian; Svensson, Birgitta; Engblom, Johan; Ruzgas, Tautgirdas

2017-07-15

A skin covered oxygen electrode, SCOE, was constructed with the aim to study the enzyme catalase, which is part of the biological antioxidative system present in skin. The electrode was exposed to different concentrations of H 2 O 2 and the amperometric current response was recorded. The observed current is due to H 2 O 2 penetration through the outermost skin barrier (referred to as the stratum corneum, SC) and subsequent catalytic generation of O 2 by catalase present in the underlying viable epidermis and dermis. By tape-stripping the outermost skin layers we demonstrate that SC is a considerable diffusion barrier for H 2 O 2 penetration. Our experiments also indicate that skin contains a substantial amount of catalase, which is sufficient to detoxify H 2 O 2 that reaches the viable epidermis after exposure of skin to high concentrations of peroxide (0.5-1mM H 2 O 2 ). Further, we demonstrate that the catalase activity is reduced at acidic pH, as compared with the activity at pH 7.4. Finally, experiments with often used penetration enhancer thymol shows that this compound interferes with the catalase reaction. Health aspect of this is briefly discussed. Summarizing, the results of this work show that the SCOE can be utilized to study a broad spectrum of issues involving the function of skin catalase in particular, and the native biological antioxidative system in skin in general. Copyright © 2017 Elsevier B.V. All rights reserved.

Mechanistic Analysis of Human Skin Distribution and Follicular Targeting of Adapalene-Loaded Biodegradable Nanospheres With an Insight Into Hydrogel Matrix Influence, In Vitro Skin Irritation, and In Vivo Tolerability.

PubMed

Sallam, Marwa Ahmed; Marín Boscá, María Teresa

2017-10-01

This work aimed at the development of a biocompatible, non-oily nanomedicine for follicular delivery of adapalene (AD) ameliorating its irritation potential for convenient localized topical treatment of acne vulgaris. AD was efficiently incorporated into poly-ε-caprolactone nanospheres (NS) with an encapsulation efficiency of 84.73% ± 1.52%, a particle size of 107.5 ± 8.19 nm, and zeta potential of -13.1 mV demonstrating a sustained-release behavior. The AD-NS were embedded in either hydroxypropyl methylcellulose (HPMC) or hyaluronate (HA) gel. The ex vivo human skin dermatokinetics of AD from each system was studied. The nanoparticles dispersion showed significantly higher AD retention in the epidermis and dermis than AD suspension. NS-HPMC decreased whereas NS-HA increased AD retained in all the skin layers. The fate of the NS and the role of the hydrogel in modulating skin distribution was evaluated by confocal laser scanning microscopy (CLSM) imaging of fluorescently labeled NS. CLSM illustrated follicular localization of the florescent NS. HPMC gel restricted the presence of NS to the stratum corneum and epidermis. HA gel enhanced the penetration of NS to all the skin layers. In vitro skin irritation using human dermal fibroblasts and in vivo animal tolerability studies were performed. Accordingly, HA gel-dispersed AD-NS presented a nonirritant compromised cosmeceutical formulation suitable for oily acneic skin. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Barrier Requirements as the Evolutionary “Driver” of Epidermal Pigmentation in Humans

PubMed Central

ELIAS, PETER M.; MENON, GOPINATHAN; WETZEL, BRUCE K.; WILLIAMS, JOHN (JACK) W.

2011-01-01

Current explanations for the development of epidermal pigmentation during human evolution are not tenable as stand-alone hypotheses. Accordingly, we assessed instead whether xeric- and UV-B-induced stress to the epidermal permeability barrier, critical to survival in a terrestrial environment, could have “driven” the development of epidermal pigmentation. (1) Megadroughts prevailed in central Africa when hominids expanded into open savannahs [≈1.5–0.8 million years ago], resulting in sustained exposure to both extreme aridity and erythemogenic UV-B, correlating with genetic evidence that pigment developed ≈1.2 million years ago. (2) Pigmented skin is endowed with enhanced permeability barrier function, stratum corneum integrity/cohesion, and a reduced susceptibility to infections. The enhanced function of pigmented skin can be attributed to the lower pH of the outer epidermis, likely due to the persistence of (more-acidic) melanosomes into the outer epidermis, as well as the conservation of genes associated with eumelanin synthesis and melanosome acidification (e.g., TYR, OCA2 [p protein], SLC24A5, SLC45A2, MATP) in pigmented populations. Five keratinocyte-derived signals (stem cell factor⇒KIT; FOXn1⇒FGF2; IL-1α, NGF, and p53) are potential candidates to have stimulated the sequential development of epidermal pigmentation in response to stress to the barrier. We summarize evidence here that epidermal interfollicular pigmentation in early hominids likely evolved in response to stress to the permeability barrier. PMID:20209486

Variation in the activities of late stage filaggrin processing enzymes, calpain-1 and bleomycin hydrolase, together with pyrrolidone carboxylic acid levels, corneocyte phenotypes and plasmin activities in non-sun-exposed and sun-exposed facial stratum corneum of different ethnicities.

PubMed

Raj, N; Voegeli, R; Rawlings, A V; Summers, B; Munday, M R; Lane, M E

2016-12-01

Knowledge of the ethnic differences and effects of photodamage on the relative amounts of natural moisturizing factor (NMF) together with filaggrin processing enzymes in facial stratum corneum is limited. Our aim was to characterize the activities of calpain-1 (C-1), bleomycin hydrolase (BH) and the levels of pyrrolidone carboxylic acid (PCA) as a marker for total NMF levels and to relate them to plasmin activities and corneocyte maturation. Enzyme activities, PCA levels and corneocyte maturation were determined from facial tape strippings of photoexposed cheek and photoprotected post-auricular areas (PA) of healthy Caucasian (C), Black African (BA) and albino African (AA) female subjects living in South Africa. PCA concentration levels were of the order AA > BA > C subjects, and the highest activities of BH were present in the AA subjects. BH activities were greater on the photoexposed sites for the BA and C subjects, but they were only numerically elevated in the AA subjects. Photoprotected sites had an increase in C-1 activity in pigmented groups (C and BA), whereas in the AA subjects, the opposite was measured. Plasmin activities were greater on the cheek compared with the PA site for the AA and C subjects, but the activity was low in the BA subjects. In both test sites, the AA, but not the BA and C subjects, had smaller, parakeratotic and less mature corneocytes. Variation in PCA levels has been found for different ethnic groups in this study (AA > BA > C subjects). The values in the AA subjects are surprising as one might expect that the lack of pigmentation, and thereby increased photodamage, might lead to lower levels. Increased BH, but not C-1 activity, was observed in the AA subjects indicating that BH is associated with PCA production to a greater extent. Surprisingly, corneocyte maturation is still impaired with elevated PCA levels in AA subjects. The higher levels of plasmin and BH activities on the cheeks, especially for AA and C subjects, suggest

Solar radiation (PAR and UVA) and water temperature in relation to biochemical performance of Gelidium corneum (Gelidiales, Rhodophyta) in subtidal bottoms off the Basque coast

NASA Astrophysics Data System (ADS)

Quintano, Endika; Ganzedo, Unai; Díez, Isabel; Figueroa, Félix L.; Gorostiaga, José M.

2013-10-01

Gelidium corneum (Hudson) J.V. Lamouroux is a very important primary producer in the Cantabrian coastal ecosystem. Some local declines in their populations have been recently detected in the Basque coast. Occurrences of yellowing and an unusual branch breakdown pattern have also been reported for some G. corneum populations. In order to gain further insight into those environmental stressors operating at a local scale, here we investigate if shallow subtidal populations of G. corneum living under potentially different conditions of irradiance (PAR and UVA) and water temperature exhibit differences in some biochemical indicators of stress, namely C:N, antioxidant activity (radical cation of 2,2‧-azino-bis (3-ethylbenzothiazoline-6-sulfonate); ABTS+ assay) and mycosporine-like amino acids (MAAs) (Asterine 330 and Palythine). We hypothesised that G. corneum subjected to higher ambient levels of irradiance and water temperature would show higher C:N ratios, lower antioxidant activity and higher MAA concentrations. Our results partially support this hypothesis. We found that G. corneum exposed to increased levels of irradiance (PAR, UVA) exhibited greater C:N ratios and lower antioxidant activity (higher IC50), whereas no relationship was found regarding MAAs. No differences in biochemical performance in relation to temperature were detected among G. corneum exposed to comparable high light. Similarly, G. corneum growing under lower UVA radiation levels showed no differences in any of the measured biochemical variables with regard to PAR and water temperature. These findings suggest that, among the environmental factors examined, UVA radiation may be an important driver in regulating the along-shore variation in G. corneum biochemical performance. Therefore, the role of irradiance, especially UV radiation, in potential future alterations in Cantabrian G. corneum populations cannot be ruled out as a potential underlying factor.

Fluorescence dynamics of human epidermis (ex vivo) and skin (in vivo)

NASA Astrophysics Data System (ADS)

Salomatina, Elena V.; Pravdin, Alexander B.

2003-10-01

The temporal behavior of autofluorescence of human skin and epidermis under continuous UV-irradiation has been studied. Fluorescence spectra and kinetic curves of fluorescence intensity have been obtained. The fluorescence intensity recovery after dark period also has been examined. The vitiligo skin and epidermis were used for comparing their spectra with reflectance and fluorescence spectra of healthy skin. The epidermal samples were prepared using surface epidermis stripping technique. It has been concluded that fluorophores being undergone the UVA photobleaching are actually present in epidermal layer, and immediate pigment darkening does contribute, no less than a half of magnitude, to the autofluorescence decrease under continuous UVA irradiation.

Biometrological assessment of the preventive effect of a miconazole spray powder on athlete's foot.

PubMed

Piérard, G E; Wallace, R; De Doncker, P

1996-09-01

Prevention of athlete's foot is a difficult problem. Using non-invasive biometrological methods, we evaluated the changes induced in the stratum corneum by a 3-week treatment with miconazole spray powder. A total of 16 athletes apparently at risk of developing tinea pedis, but without any evidence for the disease at the time of inclusion, participated in the study. They applied the medicated powder to one foot daily, while the other foot remained untreated to serve as a control. No adverse events occurred. In comparison with the control site, the capacitance of the toeweb skin was significantly reduced by the treatment. The ex vivo bioassay of dermatophyte culture on stratum corneum demonstrated a significant inhibition of growth of Trichophyton mentagrophytes var. interdigital at the treated site. The results of this study provide indirect evidence that the regular use of miconazole spray powder decreases the risk of developing athlete's foot.

Transdermal delivery of therapeutic agent

NASA Technical Reports Server (NTRS)

Kwiatkowski, Krzysztof C. (Inventor); Hayes, Ryan T. (Inventor); Magnuson, James W. (Inventor); Giletto, Anthony (Inventor)

2008-01-01

A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

Early-life risk factors for occurrence of atopic dermatitis during the first year.

PubMed

Sugiyama, Mikio; Arakawa, Hirokazu; Ozawa, Kiyoshi; Mizuno, Takahisa; Mochizuki, Hiroyuki; Tokuyama, Kenichi; Morikawa, Akihiro

2007-03-01

In a prospective birth cohort study, we sought to identify perinatal predictors of the occurrence of atopic dermatitis in the first year of life. Associations of family history, infection during pregnancy, cord blood cytokine concentrations, and skin function parameters with atopic dermatitis were analyzed. Stratum corneum hydration was measured with an impedance meter until 5 days after delivery and again at 1 month. Complete data were obtained for 213 infants, including 27 diagnosed by a physician as having atopic dermatitis during their first year and 26 diagnosed as having infantile eczema during their first month. The risk of atopic dermatitis during the first year of life was related to maternal atopic dermatitis, lower concentrations of macrophage inflammatory protein-1beta in cord blood, and greater skin moisture in the surface and stratum corneum of the forehead and cheek at 1 month of age but not to viral or bacterial infection during pregnancy or breastfeeding. Paternal hay fever was associated negatively with the development of atopic dermatitis. High concentrations of interleukin-5, interleukin-17, and macrophage chemotactic protein-1 and only surface moisture in the cheek were associated with greater risk of infantile eczema in the first month. The association of atopic dermatitis in infancy with reduced neonatal macrophage inflammatory protein-1beta levels suggests a link with immature immune responses at birth. Stratum corneum barrier disruption in atopic dermatitis may involve impairment of cutaneous adaptation to extrauterine life. The majority of risk factors had different effects on infant eczema and atopic dermatitis, indicating different causes.

Effect of olive and sunflower seed oil on the adult skin barrier: implications for neonatal skin care.

PubMed

Danby, Simon G; AlEnezi, Tareq; Sultan, Amani; Lavender, Tina; Chittock, John; Brown, Kirsty; Cork, Michael J

2013-01-01

Natural oils are advocated and used throughout the world as part of neonatal skin care, but there is an absence of evidence to support this practice. The goal of the current study was to ascertain the effect of olive oil and sunflower seed oil on the biophysical properties of the skin. Nineteen adult volunteers with and without a history of atopic dermatitis were recruited into two randomized forearm-controlled mechanistic studies. The first cohort applied six drops of olive oil to one forearm twice daily for 5 weeks. The second cohort applied six drops of olive oil to one forearm and six drops of sunflower seed oil to the other twice daily for 4 weeks. The effect of the treatments was evaluated by determining stratum corneum integrity and cohesion, intercorneocyte cohesion, moisturization, skin-surface pH, and erythema. Topical application of olive oil for 4 weeks caused a significant reduction in stratum corneum integrity and induced mild erythema in volunteers with and without a history of atopic dermatitis. Sunflower seed oil preserved stratum corneum integrity, did not cause erythema, and improved hydration in the same volunteers. In contrast to sunflower seed oil, topical treatment with olive oil significantly damages the skin barrier, and therefore has the potential to promote the development of, and exacerbate existing, atopic dermatitis. The use of olive oil for the treatment of dry skin and infant massage should therefore be discouraged. These findings challenge the unfounded belief that all natural oils are beneficial for the skin and highlight the need for further research. © 2012 Wiley Periodicals, Inc.

Proteomic profiling reveals candidate markers for arsenic-induced skin keratosis.

PubMed

Guo, Zhiling; Hu, Qin; Tian, Jijing; Yan, Li; Jing, Chuanyong; Xie, Heidi Qunhui; Bao, Wenjun; Rice, Robert H; Zhao, Bin; Jiang, Guibin

2016-11-01

Proteomics technology is an attractive biomarker candidate discovery tool that can be applied to study large sets of biological molecules. To identify novel biomarkers and molecular targets in arsenic-induced skin lesions, we have determined the protein profile of arsenic-affected human epidermal stratum corneum by shotgun proteomics. Samples of palm and foot sole from healthy subjects were analyzed, demonstrating similar protein patterns in palm and sole. Samples were collected from the palms of subjects with arsenic keratosis (lesional and adjacent non-lesional samples) and arsenic-exposed subjects without lesions (normal). Samples from non-exposed healthy individuals served as controls. We found that three proteins in arsenic-exposed lesional epidermis were consistently distinguishably expressed from the unaffected epidermis. One of these proteins, the cadherin-like transmembrane glycoprotein, desmoglein 1 (DSG1) was suppressed. Down-regulation of DSG1 may lead to reduced cell-cell adhesion, resulting in abnormal epidermal differentiation. The expression of keratin 6c (KRT6C) and fatty acid binding protein 5 (FABP5) were significantly increased. FABP5 is an intracellular lipid chaperone that plays an essential role in fatty acid metabolism in human skin. This raises a possibility that overexpression of FABP5 may affect the proliferation or differentiation of keratinocytes by altering lipid metabolism. KRT6C is a constituent of the cytoskeleton that maintains epidermal integrity and cohesion. Abnormal expression of KRT6C may affect its structural role in the epidermis. Our findings suggest an important approach for future studies of arsenic-mediated toxicity and skin cancer, where certain proteins may represent useful biomarkers of early diagnoses in high-risk populations and hopefully new treatment targets. Further studies are required to understand the biological role of these markers in skin pathogenesis from arsenic exposure. Copyright © 2016 Elsevier Ltd

The caspase-1 inhibitor CARD18 is specifically expressed during late differentiation of keratinocytes and its expression is lost in lichen planus.

PubMed

Qin, Haihong; Jin, Jiang; Fischer, Heinz; Mildner, Michael; Gschwandtner, Maria; Mlitz, Veronika; Eckhart, Leopold; Tschachler, Erwin

2017-08-01

CARD18 contains a caspase recruitment domain (CARD) via which it binds to caspase-1 and thereby inhibits caspase-1-mediated activation of the pro-inflammatory cytokine interleukin (IL)-1β. To determine the expression profile and the role of CARD18 during differentiation of keratinocytes and to compare the expression of CARD18 in normal skin and in inflammatory skin diseases. Human keratinocytes were induced to differentiate in monolayer and in 3D skin equivalent cultures. In some experiments, CARD18-specific siRNAs were used to knock down expression of CARD18. CARD18 mRNA levels were determined by quantitative real-time PCR, and CARD18 protein was detected by Western blot and immunofluorescence analyses. In situ expression was analyzed in skin biopsies obtained from healthy donors and patients with psoriasis and lichen planus. CARD18 mRNA was expressed in the epidermis at more than 100-fold higher levels than in any other human tissue. Within the epidermis, CARD18 was specifically expressed in the granular layer. In vitro CARD18 was strongly upregulated at both mRNA and protein levels in keratinocytes undergoing terminal differentiation. In skin equivalent cultures the expression of CARD18 was efficiently suppressed by siRNAs without impairing stratum corneum formation. Epidermal expression of CARD18 was increased after ultraviolet (UV)B irradiation of skin explants. In skin biopsies of patients with psoriasis no consistent regulation of CARD18 expression was observed, however, in lesional epidermis of patients with lichen planus, CARD18 expression was either greatly diminished or entirely absent whereas in non-lesional areas expression was comparable to normal skin. Our results identify CARD18 as a differentiation-associated keratinocyte protein that is altered in abundance by UV stress. Its downregulation in lichen planus indicates a potential role in inflammatory reactions of the epidermis in this disease. Copyright © 2017 Japanese Society for Investigative

Performance evaluation of multi-stratum resources integrated resilience for software defined inter-data center interconnect.

PubMed

Yang, Hui; Zhang, Jie; Zhao, Yongli; Ji, Yuefeng; Wu, Jialin; Lin, Yi; Han, Jianrui; Lee, Young

2015-05-18

Inter-data center interconnect with IP over elastic optical network (EON) is a promising scenario to meet the high burstiness and high-bandwidth requirements of data center services. In our previous work, we implemented multi-stratum resources integration among IP networks, optical networks and application stratums resources that allows to accommodate data center services. In view of this, this study extends to consider the service resilience in case of edge optical node failure. We propose a novel multi-stratum resources integrated resilience (MSRIR) architecture for the services in software defined inter-data center interconnect based on IP over EON. A global resources integrated resilience (GRIR) algorithm is introduced based on the proposed architecture. The MSRIR can enable cross stratum optimization and provide resilience using the multiple stratums resources, and enhance the data center service resilience responsiveness to the dynamic end-to-end service demands. The overall feasibility and efficiency of the proposed architecture is experimentally verified on the control plane of our OpenFlow-based enhanced SDN (eSDN) testbed. The performance of GRIR algorithm under heavy traffic load scenario is also quantitatively evaluated based on MSRIR architecture in terms of path blocking probability, resilience latency and resource utilization, compared with other resilience algorithms.

Bed structure (frond bleaching, density and biomass) of the red alga Gelidium corneum under different irradiance levels

NASA Astrophysics Data System (ADS)

Quintano, E.; Díez, I.; Muguerza, N.; Figueroa, F. L.; Gorostiaga, J. M.

2017-12-01

In recent decades a decline in the foundation species Gelidium corneum (Hudson) J. V. Lamouroux has been detected along the Basque coast (northern Spain). This decline has been attributed to several factors, but recent studies have found a relationship between high irradiance and the biochemical and physiological stress of G. corneum. Since physiological responses to changes in light occur well before variations in morphology, the present study seeks to use a size-class demographic approach to investigate whether shallow subtidal populations of G. corneum off the Basque coast show different frond bleaching, density and biomass under different irradiance conditions. The results revealed that the bleaching incidence and cover were positively related to irradiance, whereas biomass was negatively related. The effect of the irradiance level on frond density was found to vary with size-class, i.e. fronds up to 15 cm showed greater densities under high light conditions (126.6 to 262.2 W m- 2) whereas the number of larger fronds (> 20 cm) per unit area was lower. In conclusion, the results of the present study suggest that irradiance might be a key factor for controlling along-shore bleaching, frond density and biomass in G. corneum. Further research should be carried out on the physiology of this canopy species in relation to its bed structure and on the interaction of irradiance and other abiotic (nutrients, temperature, wave energy) and biotic factors (grazing pressure).

The role of the conformational profile of polysaccharides on skin penetration: the case of hyaluronan and its sulfates.

PubMed

Cilurzo, Francesco; Vistoli, Giulio; Gennari, Chiara G M; Selmin, Francesca; Gardoni, Fabrizio; Franzè, Silvia; Campisi, Monica; Minghetti, Paola

2014-04-01

The literature data suggest the capacity of biomacromolecules to permeate the human skin, even though such a transdermal permeation appears to be governed by physicochemical parameters which are significantly different compared to those ruling the skin permeation of small molecules. On these grounds, the present study was undertaken to investigate the in vitro diffusion properties through the human epidermis of hyaluronic acid and their sulfates. Low- and medium-molecular-weight hyaluronic acids and the corresponding derivatives at two degrees of sulfation were then tested. In vitro studies evidenced that the sulfated polymers permeate better than the corresponding hyaluronic acid, despite their vastly greater polarity, while the observed permeation markedly decreases when increasing the polymer's molecular weight regardless of the sulfation degree. Using a fluorescent-labeled polysaccharide, it was also evidenced that hyaluronans have a great affinity for corneocytes and likely cross the stratum corneum mainly through a transcellular route. The molecular-dynamics study revealed how the observed permeations for the investigated polysaccharides can be rationalized by monitoring their conformational profiles, since the permeation was found to be directly related to their capacity to assume extended and flexible conformations. Copyright © 2014 Verlag Helvetica Chimica Acta AG, Zürich.

In vitro human skin permeation and decontamination of 2-chloroethyl ethyl sulfide (CEES) using Dermal Decontamination Gel (DDGel) and Reactive Skin Decontamination Lotion (RSDL).

PubMed

Cao, Yachao; Hui, Xiaoying; Zhu, Hanjiang; Elmahdy, Akram; Maibach, Howard

2018-07-01

This study compared the efficiency for in vitro human skin decontamination using DDGel and RSDL. Experiments were performed using in vitro human skin models, in which skin was mounted onto Flow-Through diffusion cells. The mass of 14 -C CEES removed from skin surface after decontamination was quantitated by measuring radioactivity with a liquid scintillation spectrometer. Both decontaminants removed more than 82% of CEES from skin. DDGel skin decontamination significantly reduced toxicant amount when compared to RSDL. Mean CEES remaining in stratum corneum (SC), viable epidermis, dermis, and systemic absorption of DDGel and RSDL were, 0.12 and 0.55% (P < 0.01), 0.31 and 0.95% (p < 0.01), 1.08 and 2.92% (p < 0.05), 3.13 and 6.34% (p < 0.05), respectively. DDGel showed higher decontamination efficiency (twice decontamination efficacy factor, DEF) than RSDL and efficiently removed chemicals from the skin surface, importantly back-extracted from the SC, and significantly reduced both chemical penetration into skin and systemic absorption. Thus, DDGel can offer a potential as a next generation skin decontamination platform technology for military and civilian applications. Copyright © 2018 Elsevier B.V. All rights reserved.

Chymotryptic specificity determinants in the 1.0 Å structure of the zinc-inhibited human tissue kallikrein 7

PubMed Central

Debela, Mekdes; Hess, Petra; Magdolen, Viktor; Schechter, Norman M.; Steiner, Thomas; Huber, Robert; Bode, Wolfram; Goettig, Peter

2007-01-01

hK7 or human stratum corneum chymotryptic enzyme belongs to the human tissue kallikrein (hKs) serine proteinase family and is strongly expressed in the upper layers of the epidermis. It participates in skin desquamation but is also implicated in diverse skin diseases and is a potential biomarker of ovarian cancer. We have solved x-ray structures of recombinant active hK7 at medium and atomic resolution in the presence of the inhibitors succinyl-Ala-Ala-Pro-Phe-chloromethyl ketone and Ala-Ala-Phe-chloromethyl ketone. The most distinguishing features of hK7 are the short 70–80 loop and the unique S1 pocket, which prefers P1 Tyr residues, as shown by kinetic data. Similar to several other kallikreins, the enzyme activity is inhibited by Zn2+ and Cu2+ at low micromolar concentrations. Biochemical analyses of the mutants H99A and H41F confirm that only the metal-binding site at His99 close to the catalytic triad accounts for the noncompetitive Zn2+ inhibition type. Additionally, hK7 exhibits large positively charged surface patches, representing putative exosites for prime side substrate recognition. PMID:17909180

Probing skin interaction with hydrogen peroxide using diffuse reflectance spectroscopy

NASA Astrophysics Data System (ADS)

Zonios, George; Dimou, Aikaterini; Galaris, Dimitrios

2008-01-01

Hydrogen peroxide is an important oxidizing agent in biological systems. In dermatology, it is frequently used as topical antiseptic, it has a haemostatic function, it can cause skin blanching, and it can facilitate skin tanning. In this work, we investigated skin interaction with hydrogen peroxide, non-invasively, using diffuse reflectance spectroscopy. We observed transient changes in the oxyhaemoglobin and deoxyhaemoglobin concentrations as a result of topical application of dilute H2O2 solutions to the skin, with changes in deoxyhaemoglobin concentration being more pronounced. Furthermore, we did not observe any appreciable changes in melanin absorption properties as well as in the skin scattering properties. We also found no evidence for production of oxidized haemoglobin forms. Our observations are consistent with an at least partial decomposition of hydrogen peroxide within the stratum corneum and epidermis, with the resulting oxygen and/or remaining hydrogen peroxide inducing vasoconstriction to dermal blood vessels and increasing haemoglobin oxygen saturation. An assessment of the effects of topical application of hydrogen peroxide to the skin may serve as the basis for the development of non-invasive techniques to measure skin antioxidant capacity and also may shed light onto skin related disorders such as vitiligo.

A physiologically based mathematical model of dermal absorption in man.

PubMed

Auton, T R; Westhead, D R; Woollen, B H; Scott, R C; Wilks, M F

1994-01-01

A sound understanding of the mechanisms determining percutaneous absorption is necessary for toxicological risk assessment of chemicals contacting the skin. As part of a programme investigating these mechanisms we have developed a physiologically based mathematical model. The structure of the model parallels the multi-layer structure of the skin, with separate surface, stratum corneum and viable tissue layers. It simulates the effects of partitioning and diffusive transport between the sub-layers, and metabolism in the viable epidermis. In addition the model describes removal processes on the surface of the skin, including the effects of washing and desquamation, and rubbing off onto clothing. This model is applied to data on the penetration of the herbicide fluazifop-butyl through human skin in vivo and in vitro. Part of this dataset is used to estimate unknown model parameter values and the remainder is used to provide a partial validation of the model. Only a small fraction of the applied dose was absorbed through the skin; most of it was removed by washing or onto clothing. The model provides a quantitative description of these loss processes on the skin surface.

Fibre optic confocal imaging (FOCI) of keratinocytes, blood vessels and nerves in hairless mouse skin in vivo

PubMed Central

BUSSAU, L. J.; VO, L. T.; DELANEY, P. M.; PAPWORTH, G. D.; BARKLA, D. H.; KING, R. G.

1998-01-01

Fibre optic confocal imaging (FOCI) enabled subsurface fluorescence microscopy of the skin of hairless mice in vivo. Application of acridine orange enabled imaging of the layers of the epidermis. The corneocytes of the stratum corneum, the keratinocytes in the basal layers and redundant hair follicles were visualised at depths greater than 100 μm. Cellular and nuclear membranes of keratinocytes of the skin were visualised by the use of acridine orange and DIOC5(3). Imaging of the skin after injection of FITC-dextran revealed an extensive network of blood vessels with a size range up to 20 μm. Blood cells could be seen moving through dermal vessels and the blood circulation through the dermal vascular bed was video-taped. The fluorescent dye 4-di-2-ASP showed the presence of nerves fibres around the hair follicles and subsurface blood vessels. Comparison was made between images obtained in vivo using FOCI and in vitro scanning electron microscopy and conventional histology. FOCI offers the potential to study dynamic events in vivo, such as blood flow, skin growth, nerve regeneration and many pathological processes, in ways which have not previously been possible. PMID:9643419

Climate change and cutaneous water loss of birds.

PubMed

Williams, Joseph B; Muñoz-Garcia, Agustí; Champagne, Alex

2012-04-01

There is a crucial need to understand how physiological systems of animals will respond to increases in global air temperature. Water conservation may become more important for some species of birds, especially those living in deserts. Lipids of the stratum corneum (SC), the outer layer of the epidermis, create the barrier to water vapor diffusion, and thus control cutaneous water loss (CWL). An appreciation of the ability of birds to change CWL by altering lipids of the skin will be important to predict responses of birds to global warming. The interactions of these lipids are fundamental to the modulation of water loss through skin. Cerebrosides, with their hexose sugar moiety, are a key component of the SC in birds, but how these lipids interact with other lipids of the SC, or how they form hydrogen bonds with water molecules, to form a barrier to water vapor diffusion remains unknown. An understanding of how cerebrosides interact with other lipids of the SC, and of how the hydroxyl groups of cerebrosides interact with water molecules, may be a key to elucidating the control of CWL by the SC.

Analysis of in vivo penetration of textile dyes causing allergic reactions

NASA Astrophysics Data System (ADS)

Lademann, J.; Patzelt, A.; Worm, M.; Richter, H.; Sterry, W.; Meinke, M.

2009-10-01

Contact allergies to textile dyes are common and can cause severe eczema. In the present study, we investigated the penetration of a fluorescent textile dye, dissolved from a black pullover, into the skin of one volunteer during perspiration and nonperspiration. Previously, wearing this pullover had induced a severe contact dermatitis in an 82-year old woman, who was not aware of her sensitization to textile dyes. The investigations were carried out by in vivo laser scanning microscopy. It could be demonstrated that the dye was eluted from the textile material by sweat. Afterwards, the dye penetrated into the stratum corneum and into the hair follicles. Inside the hair follicles, the fluorescent signal was still detectable after 24 h, whereas it was not verifiable anymore in the stratum corneum, Laser scanning microscopy represents an efficient tool for in vivo investigation of the penetration and storage of topically applied substances and allergens into the human skin and reveals useful hints for the development and optimization of protection strategies.

Transdermal delivery of biomacromolecules using lipid-like nanoparticles

NASA Astrophysics Data System (ADS)

Bello, Evelyn A.

The transdermal delivery of biomacromolecules, including proteins and nucleic acids, is challenging, owing to their large size and the penetration-resistant nature of the stratum corneum. Thus, an urgent need exists for the development of transdermal delivery methodologies. This research focuses on the use of cationic lipid-like nanoparticles (lipidoids) for the transdermal delivery of proteins, and establishes an in vitro model for the study. The lipidoids used were first combinatorially designed and synthesized; afterwards, they were employed for protein encapsulation in a vesicular system. A skin penetration study demonstrated that lipidoids enhance penetration depth in a pig skin model, overcoming the barrier that the stratum corneum presents. This research has successfully identified active lipidoids capable of efficiently penetrating the skin; therefore, loading proteins into lipidoid nanoparticles will facilitate the transdermal delivery of proteins. Membrane diffusion experiments were used to confirm the results. This research has confirmed that lipidoids are a suitable material for transdermal protein delivery enhancement.

A new methodology for evaluating the damage to the skin barrier caused by repeated application and removal of adhesive dressings.

PubMed

Waring, Mike; Bielfeldt, Stephan; Mätzold, Katja; Wilhelm, Klaus-Peter

2013-02-01

Chronic wounds require frequent dressing changes. Adhesive dressings used for this indication can be damaging to the stratum corneum, particularly in the elderly where the skin tends to be thinner. Understanding the level of damage caused by dressing removal can aid dressing selection. This study used a novel methodology that applied a stain to the skin and measured the intensity of that stain after repeated application and removal of a series of different adhesive types. Additionally, a traditional method of measuring skin barrier damage (transepidermal water loss) was also undertaken and compared with the staining methodology. The staining methodology and measurement of transepidermal water loss differentiated the adhesive dressings, showing that silicone adhesives caused least trauma to the skin. The staining methodology was shown to be as effective as transepidermal water loss in detecting damage to the stratum corneum and was shown to detect disruption of the barrier earlier than the traditional technique. © 2012 John Wiley & Sons A/S.

Gentle cleansing and moisturizing for patients with atopic dermatitis and sensitive skin.

PubMed

Cheong, Wai Kwong

2009-01-01

Atopic dermatitis is a common condition characterized by pruritus, inflammation, and dryness of the skin. Inflammation disrupts the barrier function of the stratum corneum, predisposing the skin to be dry, and increases susceptibility to irritants and secondary bacterial infection. Sensitive skin is common, reported by 40-50% of women and 30% of men in the US, Europe, and Japan. Basic requirements in managing eczema and sensitive skin include effective cleansers that do not compromise skin barrier integrity, alleviation of skin dryness, and restoration of skin barrier function through the use of therapeutic moisturizers. The selection of a skin cleanser is therefore an important part of managing these conditions. Studies have reported clinical improvement with the use of soap-free cleansers in combination with topical treatments. While topical corticosteroids and immunosuppressive agents are mainstays of treatment for atopic dermatitis, therapeutic moisturizers are important adjuncts. Moisturizers improve skin hydration, reduce susceptibility to irritation, restore the integrity of the stratum corneum, and enhance the efficacy of topical corticosteroids.

Enhancement of transdermal protein delivery by photothermal effect of gold nanorods coated on polysaccharide-based hydrogel.

PubMed

Haine, Aung Thu; Koga, Yuki; Hashimoto, Yuta; Higashi, Taishi; Motoyama, Keiichi; Arima, Hidetoshi; Niidome, Takuro

2017-10-01

Transdermal protein delivery is a useful and attractive method for protein therapy and dermal vaccination. However, this delivery method is restricted by the low permeability of the stratum corneum. The purpose of this study was to develop a transdermal delivery system for enhancement of protein permeability into the skin. First, we prepared a transparent gel patch made of polysaccharides with gold nanorods on the gel surface and fluorescein isothiocyanate-modified ovalbumin (FITC-OVA) inside. Next, the gel patch was placed on mouse skin to allow contact with the coated gold nanorods, and irradiated by a continuous-wave laser. The laser irradiation heated the gold nanorods and the skin temperature increased to 43°C, resulting in enhanced translocation of FITC-OVA into the skin. These results confirmed the capability of the transdermal protein delivery system to perforate the stratum corneum and thus facilitate the passage of proteins across the skin. Copyright © 2017 Elsevier B.V. All rights reserved.

Shaping the Skin: The Interplay of Mesoscale Geometry and Corneocyte Swelling

NASA Astrophysics Data System (ADS)

Evans, Myfanwy E.; Roth, Roland

2014-01-01

The stratum corneum, the outer layer of mammalian skin, provides a remarkable barrier to the external environment, yet it has highly variable permeability properties where it actively mediates between inside and out. On prolonged exposure to water, swelling of the corneocytes (skin cells composed of keratin intermediate filaments) is the key process by which the stratum corneum controls permeability and mechanics. As for many biological systems with intricate function, the mesoscale geometry is optimized to provide functionality from basic physical principles. Here we show that a key mechanism of corneocyte swelling is the interplay of mesoscale geometry and thermodynamics: given helical tubes with woven geometry equivalent to the keratin intermediate filament arrangement, the balance of solvation free energy and elasticity induces swelling of the system, importantly with complete reversibility. Our result remarkably replicates macroscopic experimental data of native through to fully hydrated corneocytes. This finding not only highlights the importance of patterns and morphology in nature but also gives valuable insight into the functionality of skin.

Transdermal Delivery of siRNA through Microneedle Array

NASA Astrophysics Data System (ADS)

Deng, Yan; Chen, Jiao; Zhao, Yi; Yan, Xiaohui; Zhang, Li; Choy, Kwongwai; Hu, Jun; Sant, Himanshu J.; Gale, Bruce K.; Tang, Tao

2016-02-01

Successful development of siRNA therapies has significant potential for the treatment of skin conditions (alopecia, allergic skin diseases, hyperpigmentation, psoriasis, skin cancer, pachyonychia congenital) caused by aberrant gene expression. Although hypodermic needles can be used to effectively deliver siRNA through the stratum corneum, the major challenge is that this approach is painful and the effects are restricted to the injection site. Microneedle arrays may represent a better way to deliver siRNAs across the stratum corneum. In this study, we evaluated for the first time the ability of the solid silicon microneedle array for punching holes to deliver cholesterol-modified housekeeping gene (Gapdh) siRNA to the mouse ear skin. Treating the ear with microneedles showed permeation of siRNA in the skin and could reduce Gapdh gene expression up to 66% in the skin without accumulation in the major organs. The results showed that microneedle arrays could effectively deliver siRNA to relevant regions of the skin noninvasively.

Coffee polyphenols extracted from green coffee beans improve skin properties and microcirculatory function.

PubMed

Fukagawa, Satoko; Haramizu, Satoshi; Sasaoka, Shun; Yasuda, Yuka; Tsujimura, Hisashi; Murase, Takatoshi

2017-09-01

Coffee polyphenols (CPPs), including chlorogenic acid, exert various physiological activities. The purpose of this study was to investigate the effects of CPPs on skin properties and microcirculatory function in humans. In this double-blind, placebo-controlled study, 49 female subjects with mildly xerotic skin received either a test beverage containing CPPs (270 mg/100 mL/day) or a placebo beverage for 8 weeks. The ingestion of CPPs significantly lowered the clinical scores for skin dryness, decreased transepidermal water loss, skin surface pH, and increased stratum corneum hydration and the responsiveness of skin blood flow during local warming. Moreover, the amounts of free fatty acids and lactic acid in the stratum corneum significantly increased after the ingestion of CPPs. These results suggest that an 8-week intake of CPPs improve skin permeability barrier function and hydration, with a concomitant improvement in microcirculatory function, leading to efficacy in the alleviation of mildly xerotic skin.

Development of 3D imaging technique of reconstructed human epidermis with immortalized human epidermal cell line.

PubMed

Inoue, Yu; Hasegawa, Seiji; Miyachi, Katsuma; Yamada, Takaaki; Nakata, Satoru; Ipponjima, Sari; Hibi, Terumasa; Nemoto, Tomomi; Tanaka, Masahiko; Suzuki, Ryo; Hirashima, Naohide

2018-05-01

The epidermis, the outermost layer of the skin, retains moisture and functions as a physical barrier against the external environment. Epidermal cells are continuously replaced by turnover, and thus to understand in detail the dynamic cellular events in the epidermis, techniques to observe live tissues in 3D are required. Here, we established a live 3D imaging technique for epidermis models. We first obtained immortalized human epidermal cell lines which have a normal differentiation capacity and fluorescence-labelled cytoplasm or nuclei. The reconstituted 3D epidermis was prepared with these lines. Using this culture system, we were able to observe the structure of the reconstituted epidermis live in 3D, which was similar to an in vivo epidermis, and evaluate the effect of a skin irritant. This technique may be useful for dermatological science and drug development. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Intravital multiphoton tomography as an appropriate tool for non-invasive in vivo analysis of human skin affected with atopic dermatitis

NASA Astrophysics Data System (ADS)

Huck, Volker; Gorzelanny, Christian; Thomas, Kai; Mess, Christian; Dimitrova, Valentina; Schwarz, Martin; Riemann, Iris; Niemeyer, Verena; Luger, Thomas A.; König, Karsten; Schneider, Stefan W.

2011-03-01

Increasing incidence of inflammatory skin diseases such as Atopic Dermatitis (AD) has been noted in the past years. According to recent estimations around 15% of newborn subjects are affected with a disease severity that requires medical treatment. Although its pathogenesis is multifactorial, recent reports indicate that an impaired physical skin barrier predispose for the development of AD. The major part of this barrier is formed by the stratum corneum (SC) wherein corneocytes are embedded in a complex matrix of proteins and lipids. Its components were synthesized in the stratum granulosum (SG) and secreted via lamellar bodies at the SC/SG interface. Within a clinical in vivo study we focused on the skin metabolism at the SC/SG interface in AD affected patients in comparison to healthy subjects. Measurement of fluorescence life-time of NADH provides access to the metabolic state of skin. Due to the application of a 5D intravital tomographic skin analysis we facilitate the non-invasive investigation of human epidermis in the longitudinal course of AD therapy. We could ascertain by blinded analysis of 40 skin areas of 20 patients in a three month follow-up that the metabolic status at the SC/SG interface was altered in AD compromised skin even in non-lesional, apparent healthy skin regions. This illustrates an impaired skin barrier formation even at non-affected skin of AD subjects appearing promotive for the development of acute skin inflammation. Therefore, our findings allow a deeper understanding of the individual disease development and the improved management of the therapeutic intervention in clinical application.

Unitary IPSPs evoked by interneurons at the stratum radiatum-stratum lacunosum-moleculare border in the CA1 area of the rat hippocampus in vitro

PubMed Central

Vida, Imre; Halasy, Katalin; Szinyei, Csaba; Somogyi, Peter; Buhl, Eberhard H

1998-01-01

Hippocampal non-principal neurons at the stratum radiatum-stratum lacunosum-moleculare border (R-LM interneurons) of the CA1 area may constitute several cell classes and have been implicated in the generation of GABAergic unitary IPSPs. Using biocytin-filled electrodes we recorded R-LM interneurons intracellularly in vitro and determined their postsynaptic effects in concomitantly recorded pyramidal cells. Light microscopic analysis revealed four populations of R-LM interneurons with distinct axons: (1) basket cells (n= 4) with axons predominantly ramifying in the pyramidal cell layer; (2) Schaffer collateral/commissural pathway-associated interneurons (n= 10) stratifying in stratum radiatum and, to a lesser extent, stratum oriens; (3) perforant pathway-associated interneurons (n= 6) innervating the perforant path termination zone in stratum lacunosum-moleculare of the CA1 area as well as equivalent portions of the dentate gyrus and subiculum; and (4) neurogliaform interneurons (n= 2) characterized by their dense, compact axonal and dendritic arbour. Random electron microscopic sampling of synaptic targets revealed a preponderance of pyramidal neurons as postsynaptic elements. Basket cells had a synaptic target preference for somata and proximal dendrites, whereas the remainder of R-LM interneurons innervated dendritic shafts and spines. The axon of dendrite-targeting cells formed up to six putative contacts with individual postsynaptic pyramidal cells. Anatomically recovered R-LM interneurons (n= 22) had a mean resting membrane potential of -56.7 ± 3.6 mV, a membrane time constant of 12.9 ± 7.7 ms and an input resistance of 86.4 ± 29.2 MΩ. Depolarizing current pulses generally elicited overshooting action potentials (70.8 ± 6.9 mV) which had a mean duration, when measured at half-amplitude, of 0.7 ± 0.1 ms. In response to prolonged (> 200 ms) depolarizing current pulses all R-LM interneurons displayed (a varying degree of) spike frequency adaptation. Basket

Effect of various enhancers on transdermal penetration of indomethacin and urea, and relationship between penetration parameters and enhancement factors.

PubMed

Ogiso, T; Iwaki, M; Paku, T

1995-04-01

The enhancing capacity of various chemicals, which are widely recognized as enhancers, for the transdermal penetration into full-thickness rat skin of a model lipophilic drug [indomethacin (IND)] and a hydrophilic permeant (urea) was estimated by an in vitro technique. In addition, the fluidity of the stratum corneum lipids, the partitioning of IND into skin, the lipid (ceramides) extraction from the stratum corneum by enhancers, and the IND solubility in enhancer vehicle were measured and related to the enhancing capacity. In vitro permeation experiments with hairless rat skin unequivocally revealed that the enhancers varied in abilities to enhance the fluxes of both agents. Laurocapram, isopropylmyristate (IPM), sodium oleate, and cineol increased fluxes of both agents to a great extent, but N-methyl-2-pyrrolidone (NMP), N,N-diethyl-m-tolamide (DEET), and oleyl oleate were less effective acclerants. Many enhancers increased the fluidity of the lipids [with a threshold of approximately 0.6-0.8 ns at 37 degrees C in the rotational correlation time (tau c)], the skin partitioning of IND, the extraction of ceramides from the cornified cells, and the thermodynamic activity of IND in vehicle (calculated from the solubility) to varying extents. A good correlation was observed between the increase in the fluidity of stratum corneum lipids and the partitioning of IND into skin, between the increase in the fluidity and the flux or the decrease in lag time for IND, between the removal of ceramides and the skin partitioning of IND, and between the removal of ceramides and the flux of urea (p < 0.05 in all cases).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of high-fat meal intake on the pharmacokinetic profile of ivermectin in Japanese patients with scabies.

PubMed

Miyajima, Atsushi; Hirota, Takashi; Sugioka, Akihito; Fukuzawa, Masao; Sekine, Mari; Yamamoto, Yosuke; Yoshimasu, Takashi; Kigure, Akira; Anata, Taichi; Noguchi, Wataru; Akagi, Keita; Komoda, Masayo

2016-09-01

Ivermectin (IVM) is used as an anthelmintic agent in many countries. To evaluate the effect of high-fat (HF) meal intake on the pharmacokinetics of IVM, a clinical trial was conducted in Japanese patients with scabies. The patients were administrated Stromectol(®) tablets in the fasted state, and after 1 week they were also administrated it after a HF meal (fed state). After the administration, IVM concentrations in plasma and the stratum corneum were determined. The geometric mean of fed/fasted ratio of area under IVM concentration-time curve (AUC) in plasma was 1.25 (90% confidence interval, 1.09-1.43), suggesting the tendency to increased absorption after a HF meal. The fed/fasted ratio of the maximum IVM concentration in the stratum corneum was well correlated with that in plasma. In addition, no serious adverse events were observed during the trial, while a mild increase of aspartate aminotransferase and alanine aminotransferase activity in plasma was observed under the fed state in two patients. The mean AUC of IVM in plasma of those two patients were approximately threefold higher than that of the other patients at that time. On the other hand, the treatment success rate was 76.9% at 7 days after the second administration, which was comparable with the expected level. The present study not only demonstrates that HF meal intake increases the IVM concentration in plasma and the stratum corneum in Japanese patients with scabies, but also suggests the possibility that HF meals increase the risk of hepatic dysfunction by the increased exposure of IVM. © 2016 Japanese Dermatological Association.

Automated epidermis segmentation in histopathological images of human skin stained with hematoxylin and eosin

NASA Astrophysics Data System (ADS)

Kłeczek, Paweł; Dyduch, Grzegorz; Jaworek-Korjakowska, Joanna; Tadeusiewicz, Ryszard

2017-03-01

Background: Epidermis area is an important observation area for the diagnosis of inflammatory skin diseases and skin cancers. Therefore, in order to develop a computer-aided diagnosis system, segmentation of the epidermis area is usually an essential, initial step. This study presents an automated and robust method for epidermis segmentation in whole slide histopathological images of human skin, stained with hematoxylin and eosin. Methods: The proposed method performs epidermis segmentation based on the information about shape and distribution of transparent regions in a slide image and information about distribution and concentration of hematoxylin and eosin stains. It utilizes domain-specific knowledge of morphometric and biochemical properties of skin tissue elements to segment the relevant histopathological structures in human skin. Results: Experimental results on 88 skin histopathological images from three different sources show that the proposed method segments the epidermis with a mean sensitivity of 87 %, a mean specificity of 95% and a mean precision of 57%. It is robust to inter- and intra-image variations in both staining and illumination, and makes no assumptions about the type of skin disorder. The proposed method provides a superior performance compared to the existing techniques.

The epidermis coordinates auxin-induced stem growth in response to shade

PubMed Central

Procko, Carl; Burko, Yogev; Long, Jeff A.; Chory, Joanne

2016-01-01

Growth of a complex multicellular organism requires coordinated changes in diverse cell types. These cellular changes generate organs of the correct size, shape, and functionality. In plants, the growth hormone auxin induces stem elongation in response to shade; however, which cell types of the stem perceive the auxin signal and contribute to organ growth is poorly understood. Here, we blocked the transcriptional response to auxin within specific tissues to show that auxin signaling is required in many cell types for correct hypocotyl growth in shade, with a key role for the epidermis. Combining genetic manipulations in Arabidopsis thaliana with transcriptional profiling of the hypocotyl epidermis from Brassica rapa, we show that auxin acts in the epidermis in part by inducing activity of the locally acting, growth-promoting brassinosteroid pathway. Our findings clarify cell-specific auxin function in the hypocotyl and highlight the complexity of cell type interactions within a growing organ. PMID:27401556

Heterogeneous fates and dynamic rearrangement of regenerative epidermis-derived cells during zebrafish fin regeneration.

PubMed

Shibata, Eri; Ando, Kazunori; Murase, Emiko; Kawakami, Atsushi

2018-04-13

The regenerative epidermis (RE) is a specialized tissue that plays an essential role in tissue regeneration. However, the fate of the RE during and after regeneration is unknown. In this study, we performed Cre- loxP -mediated cell fate tracking and revealed the fates of a major population of the RE cells that express fibronectin 1b ( fn1b ) during zebrafish fin regeneration. Our study showed that these RE cells are mainly recruited from the inter-ray epidermis, and that they follow heterogeneous cell fates. Early recruited cells contribute to initial wound healing and soon disappear by apoptosis, while the later recruited cells contribute to the regenerated epidermis. Intriguingly, many of these cells are also expelled from the regenerated tissue by a dynamic caudal movement of the epidermis over time, and in turn the loss of epidermal cells is replenished by a global self-replication of basal and suprabasal cells in fin. De-differentiation of non-basal epidermal cells into the basal epidermal cells did not occur during regeneration. Overall, our study reveals the heterogeneous fates of RE cells and a dynamic rearrangement of the epidermis during and after regeneration. © 2018. Published by The Company of Biologists Ltd.

Epidermis architecture and material properties of the skin of four snake species

PubMed Central

Klein, Marie-Christin G.; Gorb, Stanislav N.

2012-01-01

On the basis of structural and experimental data, it was previously demonstrated that the snake integument consists of a hard, robust, inflexible outer surface (Oberhäutchen and β-layer) and softer, flexible inner layers (α-layers). It is not clear whether this phenomenon is a general adaptation of snakes to limbless locomotion or only to specific conditions, such as habitat and locomotion. The aim of the present study was to compare the structure and material properties of the outer scale layers (OSLs) and inner scale layers (ISLs) of the exuvium epidermis in four snake species specialized to live in different habitats: Lampropeltis getula californiae (terrestrial), Epicrates cenchria cenchria (generalist), Morelia viridis (arboreal) and Gongylophis colubrinus (sand-burrowing). Scanning electron microscopy (SEM) of skin cross sections revealed a strong variation in the epidermis structure between species. The nanoindentation experiments clearly demonstrated a gradient of material properties along the epidermis in the integument of all the species studied. The presence of such a gradient is a possible adaptation to locomotion and wear minimization on natural substrates. In general, the difference in both the effective elastic modulus and hardness of the OSL and ISL between species was not large compared with the difference in epidermis thickness and architecture. PMID:22896567

The outer epidermis of Avena and maize coleoptiles is not a unique target for auxin in elongation growth

NASA Technical Reports Server (NTRS)

Cleland, R. E.

1991-01-01

A controversy exists as to whether or not the outer epidermis in coleoptiles is a unique target for auxin in elongation growth. The following evidence indicates that the outer epidermis is not the only auxin-responsive cell layer in either Avena sativa L. or Zea mays L. coleoptiles. Coleoptile sections from which the epidermis has been removed by peeling elongate in response to auxin. The magnitude of the response is similar to that of intact sections provided the incubation solution contains both auxin and sucrose. The amount of elongation is independent of the amount of epidermis removed. Sections of oat coleoptiles from which the epidermis has been removed from one side are nearly straight after 22 h in auxin and sucrose, despite extensive growth of the sections. These data indicate that the outer epidermis is not a unique target for auxin in elongation growth, at least in Avena and maize coleoptiles.

Correlation of trace element concentrations between epidermis and internal organ tissues in Indo-Pacific humpback dolphins (Sousa chinensis).

PubMed

Sun, Xian; Yu, Ri-Qing; Zhang, Mei; Zhang, Xiyang; Chen, Xi; Xiao, Yousheng; Ding, Yulong; Wu, Yuping

2017-12-15

Trace element accumulation in the epidermis of cetaceans has been less studied. This study explored the feasibility of using epidermis as a surrogate tissue to evaluate internal contaminant burdens in Indo-Pacific humpback dolphin (Sousa chinensis). Eleven trace elements were analyzed in the epidermis, muscle and liver tissues from 46 individuals of dolphins stranded along the Pearl River Estuary (PRE) coast between 2007 and 2013. Trace elemental concentrations varied among the three tissues, generally with the highest concentrations found in liver tissues and lowest in the epidermis (except Zn, As, and Pb). Zn concentration in the epidermis was the highest among all tissues, indicating that Zn could be an important element for the epidermis physiology. High concentrations of Hg and Cr in liver were likely due to an excessive intake by dolphins which consumed high Hg and Cr contaminated fishes in the PRE. Hg concentrations in epidermis and muscle tissues were significantly higher in the females than in males. Concentrations of V and Pb in liver, Se and Cd in both muscle and liver, and As and Hg in all tissue samples showed significantly positive relationships with body length. Hepatic Cu concentrations were significantly negatively correlated with the body length. Hg and As concentrations in epidermis showed significantly positive correlations with those in liver tissues. Thus this study proposed that epidermis could be used as a non-invasive monitoring tissue to evaluate Hg and As bioaccumulation in internal tissues of Indo-Pacific humpback dolphins populations. Copyright © 2017 Elsevier B.V. All rights reserved.

A model for quantitative evaluation of skin damage at adhesive wound dressing removal.

PubMed

Matsumura, Hajime; Ahmatjan, Niyaz; Ida, Yukiko; Imai, Ryutaro; Wanatabe, Katsueki

2013-06-01

The removal of adhesive wound dressings from the wound surface involves a risk of damaging the intact stratum corneum and regenerating epithelium. Pain associated with the removal of wound dressings is a major issue for patients and medical personnel. Recently, wound dressings coated with a silicone adhesive have been developed to reduce such skin damage and pain on removal and they have received good evaluation in various clinical settings. However, there is neither a standard method to quantify whether or not the integrity of the stratum corneum and regenerating epithelium is retained or if both structures are damaged by the removal of wound dressings, nor are there standardised values with which to assess skin damage. We applied six different types of adhesive wound dressing on plain copy paper printed with black ink by a laser printer, removed the dressings, examined the adhesive-coated surface of the wound dressings using a high-power videoscope, and examined the stripped areas. Wound dressings coated with a silicone adhesive showed significantly less detachment of the stratum corneum and regenerating epithelium, followed by those coated with polyurethane, hydrocolloid, and acrylic adhesives. The assessment method utilised in this study revealed distinct differences between wound dressing types, but less variation in the evaluation outcome of each type. This assessment method may be useful for the evaluation of adhesive wound dressings, particularly during product development. However, further studies will be needed to examine the effectiveness of this assessment method in the clinical setting because the adherent properties of polyurethane and hydrocolloid adhesives may be altered by the absorption of water from the skin. © 2012 The Authors. International Wound Journal © 2012 John Wiley & Sons Ltd and Medicalhelplines.com Inc.

The Rheological Properties of Lipid Monolayers Modulate the Incorporation of l-Ascorbic Acid Alkyl Esters.

PubMed

Díaz, Yenisleidy de Las Mercedes Zulueta; Mottola, Milagro; Vico, Raquel V; Wilke, Natalia; Fanani, María Laura

2016-01-19

In this work, we tested the hypothesis that the incorporation of amphiphilic drugs into lipid membranes may be regulated by their rheological properties. For this purpose, two members of the l-ascorbic acid alkyl esters family (ASCn) were selected, ASC16 and ASC14, which have different rheological properties when organized at the air/water interface. They are lipophilic forms of vitamin C used in topical pharmacological preparations. The effect of the phase state of the host lipid membranes on ASCn incorporation was explored using Langmuir monolayers. Films of pure lipids with known phase states have been selected, showing liquid-expanded, liquid-condensed, and solid phases as well as pure cholesterol films in liquid-ordered state. We also tested ternary and quaternary mixed films that mimic the properties of cholesterol containing membranes and of the stratum corneum. The compressibility and shear properties of those monolayers were assessed in order to define its phase character. We found that the length of the acyl chain of the ASCn compounds induces differential changes in the rheological properties of the host membrane and subtly regulates the kinetics and extent of the penetration process. The capacity for ASCn uptake was found to depend on the phase state of the host film. The increase in surface pressure resultant after amphiphile incorporation appears to be a function of the capacity of the host membrane to incorporate such amphiphile as well as the rheological response of the film. Hence, monolayers that show a solid phase state responded with a larger surface pressure increase to the incorporation of a comparable amount of amphiphile than liquid-expanded ones. The cholesterol-containing films, including the mixture that mimics stratum corneum, allowed a very scarce ASCn uptake independently of the membrane diffusional properties. This suggests an important contribution of Cho on the maintenance of the barrier function of stratum corneum.

Epidermal differentiation in embryos of the tuatara Sphenodon punctatus (Reptilia, Sphenodontidae) in comparison with the epidermis of other reptiles.

PubMed

Alibardi, L; Gill, B J

2007-07-01

Studying the epidermis in primitive reptiles can provide clues regarding evolution of the epidermis during land adaptation in vertebrates. With this aim, the development of the skin of the relatively primitive reptile Sphenodon punctatus in representative embryonic stages was studied by light and electron microscopy and compared with that of other reptiles previously studied. The dermis organizes into a superficial and deep portion when the epidermis starts to form the first layers. At embryonic stages comparable with those of lizards, only one layer of the inner periderm is formed beneath the outer periderm. This also occurs in lizards and snakes so far studied. The outer and inner periderm form the embryonic epidermis and accumulate thick, coarse filaments (25-30 nm thick) and sparse alpha-keratin filaments as in other reptiles. Beneath the embryonic epidermis an oberhautchen and beta-cells form small horny tips that represent overlapping borders along the margin of beta-cells that overlap other beta-cells (in a tile-like arrangement). The tips resemble those of agamine lizards but at a small scale, forming a lamellate-spinulated pattern as previously described in adult epidermis. The embryonic epidermis matures by the dispersion of coarse filaments among keratin at the end of embryonic development and is shed around hatching. The presence of these matrix organelles in the embryonic epidermis of this primitive reptile further indicates that amniote epidermis acquired interkeratin matrix proteins early for land adaptation. Unlike the condition in lizards and snakes, a shedding complex is not formed in the epidermis of embryonic S. punctatus that is like that of the adult. Therefore, as in chelonians and crocodilians, the epidermis of S. punctatus also represents an initial stage that preceded the evolution of the shedding complex for moulting.

Epidermal differentiation in embryos of the tuatara Sphenodon punctatus (Reptilia, Sphenodontidae) in comparison with the epidermis of other reptiles

PubMed Central

Alibardi, L; Gill, B J

2007-01-01

Studying the epidermis in primitive reptiles can provide clues regarding evolution of the epidermis during land adaptation in vertebrates. With this aim, the development of the skin of the relatively primitive reptile Sphenodon punctatus in representative embryonic stages was studied by light and electron microscopy and compared with that of other reptiles previously studied. The dermis organizes into a superficial and deep portion when the epidermis starts to form the first layers. At embryonic stages comparable with those of lizards, only one layer of the inner periderm is formed beneath the outer periderm. This also occurs in lizards and snakes so far studied. The outer and inner periderm form the embryonic epidermis and accumulate thick, coarse filaments (25–30 nm thick) and sparse alpha-keratin filaments as in other reptiles. Beneath the embryonic epidermis an oberhautchen and beta-cells form small horny tips that represent overlapping borders along the margin of beta-cells that overlap other beta-cells (in a tile-like arrangement). The tips resemble those of agamine lizards but at a small scale, forming a lamellate-spinulated pattern as previously described in adult epidermis. The embryonic epidermis matures by the dispersion of coarse filaments among keratin at the end of embryonic development and is shed around hatching. The presence of these matrix organelles in the embryonic epidermis of this primitive reptile further indicates that amniote epidermis acquired interkeratin matrix proteins early for land adaptation. Unlike the condition in lizards and snakes, a shedding complex is not formed in the epidermis of embryonic S. punctatus that is like that of the adult. Therefore, as in chelonians and crocodilians, the epidermis of S. punctatus also represents an initial stage that preceded the evolution of the shedding complex for moulting. PMID:17532799

Acral peeling skin syndrome in two East-African siblings: case report.

PubMed

Kiprono, Samson K; Chaula, Baraka M; Naafs, Bernard; Masenga, John E

2012-03-19

Acral peeling skin syndrome is a rare autosomal recessive genodermatosis due to a missense mutation in transglutaminase 5. The skin peeling occurs at the separation of the stratum corneum from the stratum granulosum. We present a case of two siblings who developed continuous peeling of the palms and soles from the first year of life. This peeling was more severe on the soles than palms and on younger sibling than elder sibling. Peeling is worsened by occlusion and sweating. Sporadic cases of Acral Peeling Skin Syndrome occur in African population. There is variability in time of presentation and clinical severity even within families.

Production and characterization of cosmetic nanoemulsions containing Opuntia ficus-indica (L.) mill extract as moisturizing agent.

PubMed

Ribeiro, Renato Cesar de Azevedo; Barreto, Stella Maria de Andrade Gomes; Ostrosky, Elissa Aarantes; da Rocha-Filho, Pedro Alves; Veríssimo, Lourena Mafra; Ferrari, Márcio

2015-02-02

This study aimed to produce and characterize an oil in water (O/W) nanoemulsion containing Opuntia ficus-indica (L.) Mill hydroglycolic extract, as well as evaluate its preliminary and accelerated thermal stability and moisturizing efficacy. The formulations containing 0.5% of xanthan gum (FX) and 0.5% of xanthan gum and 1% of Opuntia ficus-indica MILL extract (FXE) were white, homogeneus and fluid in aspect. Both formulations were stable during preliminary and accelerated stability tests. FX and FXE presented a pH compatible to skin pH (4.5-6.0); droplet size varying from 92.2 to 233.6 nm; a polydispersion index (PDI) around 0.200 and a zeta potential from -26.71 to -47.01 mV. FXE was able to increase the water content of the stratum corneum for 5 h after application on the forearm. The O/W nanoemulsions containing 1% of Opuntia ficus-indica (L.) Mill extract presented suitable stability for at least for 60 days. Besides, this formulation was able to increase the water content of stratum corneum, showing its moisturizing efficacy.

Age-associated decrease in GDNF and its cognate receptor GFRα-1 protein expression in human skin.

PubMed

Adly, Mohamed A; Assaf, Hanan A; Hussein, Mahmoud Rezk Abdelwahed

2016-06-01

Glial cell line-derived neurotrophic factor (GDNF) and its cognate receptor (GFRα-1) are expressed in normal human skin. They are involved in murine hair follicle morphogenesis and cycling control. We hypothesize that 'GDNF and GFRα-1 protein expression in human skin undergoes age-associated alterations. To test our hypothesis, the expression of these proteins was examined in human skin specimens obtained from 30 healthy individuals representing three age groups: children (5-18 years), adults (19-60 years) and the elderly (61-81 years). Immunofluorescent and light microscopic immunohistologic analyses were performed using tyramide signal amplification and avidin-biotin complex staining methods respectively. GDNF mRNA expression was examined by RT-PCR analysis. GDNF mRNA and protein as well as GFRα-1 protein expressions were detected in normal human skin. We found significantly reduced epidermal expression of these proteins with ageing. In the epidermis, the expression was strong in the skin of children and declined gradually with ageing, being moderate in adults and weak in the elderly. In children and adults, the expression of both GDNF and GFRα-1 proteins was strongest in the stratum basale and decreased gradually towards the surface layers where it was completely absent in the stratum corneum. In the elderly, GDNF and GFRα-1 protein expression was confined to the stratum basale. In the dermis, both GDNF and GFRα-1 proteins had strong expressions in the fibroblasts, sweat glands, sebaceous glands, hair follicles and blood vessels regardless of the age. Thus there is a decrease in epidermal GDNF and GFRα-1 protein expression in normal human skin with ageing. Our findings suggest that the consequences of this is that GFRα-1-mediated signalling is altered during the ageing process. The clinical and therapeutic ramifications of these observations mandate further investigations. © 2016 The Authors. International Journal of Experimental Pathology © 2016

A histomorphological study of sarcoptic acariasis in the dog: 19 cases.

PubMed

Morris, D O; Dunstan, R W

1996-01-01

Nineteen cases of canine sarcoptic acariasis (Sarcoptes scabiei var. canis) were diagnosed histologically by identifying sarcoptic mites present in the stratum corneum. The inflammatory responses to these mites could be staged as early, fully developed, or late lesions. No histomorphological features were identified that could serve as reliable markers of infestation in the absence of a sectioned mite.

Terminal-group oxidation of retinol by mouse epidermis. Inhibition in vitro and in vivo.

PubMed Central

Connor, M J; Smit, M H

1987-01-01

Locally applied retinol is metabolized to retinoic acid in mouse epidermis in vivo. To characterize the oxidation system we investigated the ability of soluble extracts of hairless-mouse epidermis to convert retinol and retinal into retinoic acid. The extracts oxidized retinol to retinoic acid in two steps catalysed by two NAD+-dependent enzymes that were resolved on h.p.l.c. The first enzyme catalyses the reversible oxidation of retinol to retinal and is an alcohol dehydrogenase isoenzyme. The second enzyme oxidizes retinal to retinoic acid. Retinol oxidation by epidermal extracts was inhibited by the alcohol dehydrogenase inhibitor 4-methylpyrazole and by the polyene citral. The toxicity and relatively low potency at inhibiting the epidermal alcohol dehydrogenase isoenzyme curtailed the use of 4-methylpyrazole in vivo. However, citral significantly inhibited retinoic acid formation from retinol in the epidermis in vivo. The ability to inhibit the oxidation of retinol to retinoic acid in mouse epidermis provides a potential method to resolve the roles of retinol and retinoic acid in epithelial function. PMID:3663136

Diversity and wiring variability of visual local neurons in the Drosophila medulla M6 stratum

PubMed Central

Chin, An-Lun; Lin, Chih-Yung; Fu, Tsai-Feng; Dickson, Barry J; Chiang, Ann-Shyn

2014-01-01

Local neurons in the vertebrate retina are instrumental in transforming visual inputs to extract contrast, motion, and color information and in shaping bipolar-to-ganglion cell transmission to the brain. In Drosophila, UV vision is represented by R7 inner photoreceptor neurons that project to the medulla M6 stratum, with relatively little known of this downstream substrate. Here, using R7 terminals as references, we generated a 3D volume model of the M6 stratum, which revealed a retinotopic map for UV representations. Using this volume model as a common 3D framework, we compiled and analyzed the spatial distributions of more than 200 single M6-specific local neurons (M6-LNs). Based on the segregation of putative dendrites and axons, these local neurons were classified into two families, directional and nondirectional. Neurotransmitter immunostaining suggested a signal routing model in which some visual information is relayed by directional M6-LNs from the anterior to the posterior M6 and all visual information is inhibited by a diverse population of nondirectional M6-LNs covering the entire M6 stratum. Our findings suggest that the Drosophila medulla M6 stratum contains diverse LNs that form repeating functional modules similar to those found in the vertebrate inner plexiform layer. J. Comp. Neurol. 522:3795–3816, 2014. © 2014 Wiley Periodicals, Inc. PMID:24782245

Diversity and wiring variability of visual local neurons in the Drosophila medulla M6 stratum.

PubMed

Chin, An-Lun; Lin, Chih-Yung; Fu, Tsai-Feng; Dickson, Barry J; Chiang, Ann-Shyn

2014-12-01

Local neurons in the vertebrate retina are instrumental in transforming visual inputs to extract contrast, motion, and color information and in shaping bipolar-to-ganglion cell transmission to the brain. In Drosophila, UV vision is represented by R7 inner photoreceptor neurons that project to the medulla M6 stratum, with relatively little known of this downstream substrate. Here, using R7 terminals as references, we generated a 3D volume model of the M6 stratum, which revealed a retinotopic map for UV representations. Using this volume model as a common 3D framework, we compiled and analyzed the spatial distributions of more than 200 single M6-specific local neurons (M6-LNs). Based on the segregation of putative dendrites and axons, these local neurons were classified into two families, directional and nondirectional. Neurotransmitter immunostaining suggested a signal routing model in which some visual information is relayed by directional M6-LNs from the anterior to the posterior M6 and all visual information is inhibited by a diverse population of nondirectional M6-LNs covering the entire M6 stratum. Our findings suggest that the Drosophila medulla M6 stratum contains diverse LNs that form repeating functional modules similar to those found in the vertebrate inner plexiform layer. © 2014 Wiley Periodicals, Inc.

Structure and functions of keratin proteins in simple, stratified, keratinized and cornified epithelia

PubMed Central

Bragulla, Hermann H; Homberger, Dominique G

2009-01-01

Historically, the term ‘keratin’ stood for all of the proteins extracted from skin modifications, such as horns, claws and hooves. Subsequently, it was realized that this keratin is actually a mixture of keratins, keratin filament-associated proteins and other proteins, such as enzymes. Keratins were then defined as certain filament-forming proteins with specific physicochemical properties and extracted from the cornified layer of the epidermis, whereas those filament-forming proteins that were extracted from the living layers of the epidermis were grouped as ‘prekeratins’ or ‘cytokeratins’. Currently, the term ‘keratin’ covers all intermediate filament-forming proteins with specific physicochemical properties and produced in any vertebrate epithelia. Similarly, the nomenclature of epithelia as cornified, keratinized or non-keratinized is based historically on the notion that only the epidermis of skin modifications such as horns, claws and hooves is cornified, that the non-modified epidermis is a keratinized stratified epithelium, and that all other stratified and non-stratified epithelia are non-keratinized epithelia. At this point in time, the concepts of keratins and of keratinized or cornified epithelia need clarification and revision concerning the structure and function of keratin and keratin filaments in various epithelia of different species, as well as of keratin genes and their modifications, in view of recent research, such as the sequencing of keratin proteins and their genes, cell culture, transfection of epithelial cells, immunohistochemistry and immunoblotting. Recently, new functions of keratins and keratin filaments in cell signaling and intracellular vesicle transport have been discovered. It is currently understood that all stratified epithelia are keratinized and that some of these keratinized stratified epithelia cornify by forming a Stratum corneum. The processes of keratinization and cornification in skin modifications are

Evaluation of octyl p-methoxycinnamate included in liposomes and cyclodextrins in anti-solar preparations: preparations, characterizations and in vitro penetration studies

PubMed Central

de Souza de Bustamante Monteiro, Mariana Sato; Ozzetti, Rafael Antonio; Vergnanini, André Luiz; de Brito-Gitirana, Lycia; Volpato, Nadia Maria; de Freitas, Zaida Maria Faria; Ricci-Júnior, Eduardo; dos Santos, Elisabete Pereira

2012-01-01

Purpose Awareness of the harmful effects of ultraviolet radiation has led to the increasing use of sunscreens, thus, the development of safe and effective antisolar preparations is important. The inclusion of sunscreen molecules in different release systems, like liposomes (lipo) and cyclodextrins (CD) is therefore required. Methods The in vivo sun protection factor (SPF), water resistance, and in vitro transdermal penetration test of octyl p-methoxycinnamate (OMC) in different dispersions, such as OMC encapsulated in liposomes (lipo/OMC), OMC encapsulated in β-cyclodextrins (β-CD/OMC), OMC encapsulated in both release systems (lipo/OMC and β-CD/OMC), and an OMC-free formulation were determined. Results Although the formulation containing only the lipo/OMC system revealed high value of in vivo SPF (11.0 ± 1.3) and water resistance (SPF = 10.3 ± 2.2), the formulation containing both release systems (lipo/OMC + β-cyclodextrin/OMC) showed the best result in the in vivo SPF test (11.6 ± 1.6). In the penetration test, the formulation containing the lipo/OMC system had better performance, since a high amount of OMC in the epidermis (18.04 ± 1.17 μg) and a low amount of OMC in the dermis (9.4 ± 2.36 μg) were observed. These results suggest that liposomes interact with the cells of the stratum corneum, promoting retention of OMC in this layer. Conclusion According to our study, the lipo/OMC system is the most advantageous release system, due to its ability to both increase the amount of OMC in the epidermis and decrease the risk of percutaneous absorption. PMID:22787399

Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations.

PubMed

Özcan, Ipek; Azizoğlu, Erkan; Senyiğit, Taner; Özyazıcı, Mine; Özer, Özgen

2013-01-01

The objective of this study was to prepare a suitable formulation for dermal delivery of diflucortolone valerate (DFV) that would maintain the localization in skin layers without any penetration and to optimize efficiency of DFV. Drug-loaded lecithin/chitosan nanoparticles with high entrapment efficiency (86.8%), were successfully prepared by ionic interaction technique. Sustained release of DFV was achieved without any initial burst release. Nanoparticles were also incorporated into chitosan gel at different ratios for preparing a more suitable formulation for topical drug delivery with adequate viscosity. In ex-vivo permeation studies, nanoparticles increased the accumulation of DFV especially in the stratum corneum + epidermis of rat skin without any significant permeation. Retention of DFV from nanoparticle in chitosan gel formulation (0.01%) was twofold higher than commercial cream, although it contained ten times less DFV. Nanoparticles in gel formulations produced significantly higher edema inhibition in rats compared with commercial cream in in-vivo studies. Skin blanching assay using a chromameter showed vasoconstriction similar to that of the commercial product. There were no barrier function changes upon application of nanoparticles. In-vitro and in-vivo results demonstrated that lecithin/chitosan nanoparticles in chitosan gel may be a promising carrier for dermal delivery of DFV in various skin disorders.

Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations

PubMed Central

Özcan, İpek; Azizoğlu, Erkan; Şenyiğit, Taner; Özyazıcı, Mine; Özer, Özgen

2013-01-01

The objective of this study was to prepare a suitable formulation for dermal delivery of diflucortolone valerate (DFV) that would maintain the localization in skin layers without any penetration and to optimize efficiency of DFV. Drug-loaded lecithin/chitosan nanoparticles with high entrapment efficiency (86.8%), were successfully prepared by ionic interaction technique. Sustained release of DFV was achieved without any initial burst release. Nanoparticles were also incorporated into chitosan gel at different ratios for preparing a more suitable formulation for topical drug delivery with adequate viscosity. In ex-vivo permeation studies, nanoparticles increased the accumulation of DFV especially in the stratum corneum + epidermis of rat skin without any significant permeation. Retention of DFV from nanoparticle in chitosan gel formulation (0.01%) was twofold higher than commercial cream, although it contained ten times less DFV. Nanoparticles in gel formulations produced significantly higher edema inhibition in rats compared with commercial cream in in-vivo studies. Skin blanching assay using a chromameter showed vasoconstriction similar to that of the commercial product. There were no barrier function changes upon application of nanoparticles. In-vitro and in-vivo results demonstrated that lecithin/chitosan nanoparticles in chitosan gel may be a promising carrier for dermal delivery of DFV in various skin disorders. PMID:23390364

Newborn infant skin: physiology, development, and care.

PubMed

Visscher, Marty O; Adam, Ralf; Brink, Susanna; Odio, Mauricio

2015-01-01

Infant skin is critical to the newborn child's transition from the womb environment to the journey to self-sufficiency. This review provides an integrative perspective on the skin development in full term and premature infants. There is a particular focus on the role of vernix caseosa and on the implications of skin development for epidermal penetration of exogenous compounds. Healthy full-term newborn skin is well-developed and functional at birth, with a thick epidermis and well-formed stratum corneum (SC) layers. Transepidermal water loss is very low at birth, equal to, or lower than adults, indicating a highly effective skin barrier. Vernix facilitates SC development in full-term infants through a variety of mechanisms including physical protection from amniotic fluid and enzymes, antimicrobial effects, skin surface pH lowering, provision of lipids, and hydration. Premature infants, particularly those of very low birth weight, have a poor skin barrier with few cornified layers and deficient dermal proteins. They are at increased risk for skin damage, increased permeability to exogenous agents and infection. The SC barrier develops rapidly after birth but complete maturation requires weeks to months. The best methods for caring for infant skin, particularly in the diaper region, are described and related to these developmental changes. Copyright © 2015 Elsevier Inc. All rights reserved.

Urea uptake enhances barrier function and antimicrobial defense in humans by regulating epidermal gene expression

PubMed Central

Grether-Beck, Susanne; Felsner, Ingo; Brenden, Heidi; Kohne, Zippora; Majora, Marc; Marini, Alessandra; Jaenicke, Thomas; Rodriguez-Martin, Marina; Trullas, Carles; Hupe, Melanie; Elias, Peter M.; Krutmann, Jean

2012-01-01

Urea is an endogenous metabolite, known to enhance stratum corneum hydration. Yet, topical urea anecdotally also improves permeability barrier function, and it appears to exhibit antimicrobial activity. Hence, we hypothesized that urea is not merely a passive metabolite, but a small-molecule regulator of epidermal structure and function. In 21 human volunteers, topical urea improved barrier function in parallel with enhanced antimicrobial peptide (LL-37 and β-defensin-2) expression. Urea both stimulates expression of, and is transported into keratinocytes by two urea transporters, UT-A1 and UT-A2, and by aquaporin 3, 7 and 9. Inhibitors of these urea transporters block the downstream biological effects of urea, which include increased mRNA and protein levels for: (i) transglutaminase-1, involucrin, loricrin and filaggrin; (ii) epidermal lipid synthetic enzymes, and (iii) cathelicidin/LL-37 and β-defensin-2. Finally, we explored the potential clinical utility of urea, showing that topical urea applications normalized both barrier function and antimicrobial peptide expression in a murine model of atopic dermatitis (AD). Together, these results show that urea is a small-molecule regulator of epidermal permeability barrier function and antimicrobial peptide expression after transporter uptake, followed by gene regulatory activity in normal epidermis, with potential therapeutic applications in diseased skin. PMID:22418868

A modified method using the SonoPrep ultrasonic skin permeation system for sampling human interstitial fluid is compatible with proteomic techniques.

PubMed

Lecomte, Marie M J; Atkinson, Kelly R; Kay, Daniel P; Simons, Joanne L; Ingram, John R

2013-02-01

The use of biomarkers in skin is a novel diagnostic tool. Interstitial fluid (ISF) from skin provides a snapshot of proteins secreted at the time of sampling giving insights into the patient's health status. A minimally invasive technique for the transdermal collection of human ISF proteins. A low frequency ultrasonic skin permeation device (SonoPrep ultrasonic skin permeation system) was used to produce micropores in the stratum corneum through which ISF was extracted using a portable pulsed vacuum ISF collection device. On average, protein concentrations recovered ranged between 0.064 and 4.792 μg/μL (mean 1.258 μg/μL). Two-dimensional gel electrophoresis revealed that this sample type was amenable to this type of analysis. Gel images indicated that both highly abundant proteins and lower abundance proteins were isolated from the skin. Western blot analysis confirmed the presence of proteins commonly found in plasma and the epidermis. A minimally invasive method for the transdermal recovery of ISF proteins has been developed. We have demonstrated that ISF samples obtained using this approach can be analysed with proteomic techniques, such as two-dimensional gel electrophoresis and western blots, providing another tool for the identification of disease specific protein biomarkers. © 2012 John Wiley & Sons A/S.

Effect of lipophilicity on in vivo iontophoretic delivery. I. NSAIDs.

PubMed

Tashiro, Y; Shichibe, S; Kato, Y; Hayakawa, E; Itoh, K

2001-03-01

The effect of drug lipophilicity on in vivo iontophoretic transdermal absorption was evaluated. Non-steroidal anti-inflammatory drugs (NSAIDs) were selected as model drugs with a wide range of lipophilicity: salicylic acid (SA), ketoprofen (KP), naproxen (NP) and indomethacin (IM). Cathodal iontophoresis of NSAIDs was conducted in rats (0.625 mA/cm2; 90 min), and drug concentrations in skin, cutaneous vein and systemic vein were determined. Skin concentrations of NSAID were higher in the case of lipophilic drugs (SA=KP=NPKP=NP>IM). Additionally, the dependence of drug lipophilicity on systemic plasma concentration was similar to cutaneous plasma concentration. The transfer rate from skin to cutaneous vein (R(SC)) was calculated from the arterio-venous plasma concentration difference of drug in the skin. Normalized R(SC) by skin concentration (R(SC)/X(S)) yielded a negative correlation with the logarithm of n-octanol/buffer partition coefficient (Log P at pH 7.4), suggesting that transfer of NSAIDs from skin to cutaneous vein decreased with increasing lipophilicity (SA>KP=NP>IM). This correlation means that drug partitioning between stratum corneum and viable epidermis might be a dominant step.

A Hydrogel/Carbon-Nanotube Needle-Free Device for Electrostimulated Skin Drug Delivery.

PubMed

Guillet, Jean-François; Flahaut, Emmanuel; Golzio, Muriel

2017-10-06

The permeability of skin allows passive diffusion across the epidermis to reach blood vessels but this is possible only for small molecules such as nicotine. In order to achieve transdermal delivery of large molecules such as insulin or plasmid DNA, permeability of the skin and mainly the permeability of the stratum corneum skin layer has to be increased. Moreover, alternative routes that avoid the use of needles will improve the quality of life of patients. A method known as electropermeabilisation has been shown to increase skin permeability. Herein, we report the fabrication of an innovative hydrogel made of a nanocomposite material. This nanocomposite device aims to permeabilise the skin and deliver drug molecules at the same time. It includes a biocompatible polymer matrix (hydrogel) and double-walled carbon nanotubes (DWCNTs) in order to bring electrical conductivity and improve mechanical properties. Carbon nanotubes and especially DWCNTs are ideal candidates, combining high electrical conductivity with a very high specific surface area together with a good biocompatibility when included into a material. The preparation and characterization of the nanocomposite hydrogel as well as first results of electrostimulated transdermal delivery using an ex vivo mouse skin model are presented. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reconstruction of epidermis by grafting of keratinocytes cultured on polymer support--clinical study.

PubMed

Dvoránková, Barbora; Holíková, Zuzana; Vacík, Jirí; Königová, Radana; Kapounková, Zuzana; Michálek, Jirí; Prádn, Martin; Smetana, Karel

2003-03-01

Extensive wound coverage still represents a challenge for contemporary medicine. We demonstrate the results of a clinical trial of the grafting of cultured keratinocytes directly on a polymer cultivation support in the treatment of skin defects in seriously burned patients and in patients with trophic ulcers. Wound closure was evaluated clinically. The morphology and phenotypic pattern of the reconstructed epidermis, including the basal lamina, as well as the presence of Langerhans cells, were evaluated immunocytochemically using a panel of monoclonal antibodies. All layers of the reconstructed epidermis were normally differentiated (cytokeratin immunocytochemistry). The basal lamina contained collagen type IV and laminin. The reconstructed epidermis was extensively colonized by Langerhans cells. The results of the described technology are encouraging, especially in patients after a burn injury. The described procedure is suitable for the treatment of skin defects in clinical practice.

Relationship between soft stratum thickness and predominant frequency of ground based on microtremor observation data

NASA Astrophysics Data System (ADS)

Chia, Kenny; Lau, Tze Liang

2017-07-01

Despite categorized as low seismicity group, until being affected by distant earthquake ground motion from Sumatra and the recent 2015 Sabah Earthquake, Malaysia has come to realize that seismic hazard in the country is real and has the potential to threaten the public safety and welfare. The major concern in this paper is to study the effect of local site condition, where it could amplify the magnitude of ground vibration at sites. The aim for this study is to correlate the thickness of soft stratum with the predominant frequency of soil. Single point microtremor measurements were carried out at 24 selected points where the site investigation reports are available. Predominant period and frequency at each site are determined by Nakamura's method. The predominant period varies from 0.22 s to 0.98 s. Generally, the predominant period increases when getting closer to the shoreline which has thicker sediments. As far as the thickness of the soft stratum could influence the amplification of seismic wave, the advancement of micotremor observation to predict the thickness of soft stratum (h) from predominant frequency (fr) is of the concern. Thus an empirical relationship h =54.917 fr-1.314 is developed based on the microtremor observation data. The empirical relationship will be benefited in the prediction of thickness of soft stratum based on microtremor observation for seismic design with minimal cost compared to conventional boring method.

A Case of Peeling Skin Syndrome.

PubMed

Singhal, Anil K; Yadav, Devendra K; Soni, Bajrang; Arya, Savita

2017-01-01

Peeling skin syndrome is a very rare autosomal recessive disease characterized by widespread painless peeling of the skin in superficial sheets. Etiology is still unknown with an autosomal recessive inheritance. Less than 100 cases have been reported in the medical literature. We present a 32-year-old man having asymptomatic peeling of skin since birth. Sheets of skin were peeling from his neck, trunk, and extremities, following friction or rubbing especially if pre-soaked in water but sparing palm and soles. Histologically, there was epidermal separation at the level of stratum corneum, just above the stratum granulosum. This case is being presented due to its rarity.

A Case of Peeling Skin Syndrome

PubMed Central

Singhal, Anil K.; Yadav, Devendra K.; Soni, Bajrang; Arya, Savita

2017-01-01

Peeling skin syndrome is a very rare autosomal recessive disease characterized by widespread painless peeling of the skin in superficial sheets. Etiology is still unknown with an autosomal recessive inheritance. Less than 100 cases have been reported in the medical literature. We present a 32-year-old man having asymptomatic peeling of skin since birth. Sheets of skin were peeling from his neck, trunk, and extremities, following friction or rubbing especially if pre-soaked in water but sparing palm and soles. Histologically, there was epidermal separation at the level of stratum corneum, just above the stratum granulosum. This case is being presented due to its rarity. PMID:28584761

Acral peeling skin syndrome in two East-African siblings: case report

PubMed Central

2012-01-01

Background Acral peeling skin syndrome is a rare autosomal recessive genodermatosis due to a missense mutation in transglutaminase 5. The skin peeling occurs at the separation of the stratum corneum from the stratum granulosum. Case presentation We present a case of two siblings who developed continuous peeling of the palms and soles from the first year of life. This peeling was more severe on the soles than palms and on younger sibling than elder sibling. Peeling is worsened by occlusion and sweating. Conclusions Sporadic cases of Acral Peeling Skin Syndrome occur in African population. There is variability in time of presentation and clinical severity even within families. PMID:22429841

Orally administered hyaluronan affects skin dryness and epidermal thickening in photoaged hairless mice.

PubMed

Kawada, Chinatsu; Kimura, Mamoru; Masuda, Yasunobu; Nomura, Yoshihiro

2016-06-01

The oral administration of hyaluronans (HAs) (molecular weight, 300k and less than 10k) to photoaged hairless mice increased the moisture content of the stratum corneum and decreased the epidermal thickness, respectively. Furthermore, orally administered HAs suppressed the low-molecular weight of HA content of the skin. This study indicates oral administered HAs may ameliorate the skin condition resulting from photoaging.

Epidermis area detection for immunofluorescence microscopy

NASA Astrophysics Data System (ADS)

Dovganich, Andrey; Krylov, Andrey; Nasonov, Andrey; Makhneva, Natalia

2018-04-01

We propose a novel image segmentation method for immunofluorescence microscopy images of skin tissue for the diagnosis of various skin diseases. The segmentation is based on machine learning algorithms. The feature vector is filled by three groups of features: statistical features, Laws' texture energy measures and local binary patterns. The images are preprocessed for better learning. Different machine learning algorithms have been used and the best results have been obtained with random forest algorithm. We use the proposed method to detect the epidermis region as a part of pemphigus diagnosis system.

Aspects relating to stability of modified passive stratum on TiO2 nanostructure

NASA Astrophysics Data System (ADS)

Ionita, Daniela; Mazare, Anca; Portan, Diana; Demetrescu, Ioana

2011-04-01

Two kinds of nanotube structures differing from the point of view of their dimensions were obtained using anodizing in two different fluoride electrolytes and these structures were investigated regarding stability. The nanotubes have diameters of around 100 and 65 nm, respectively, and the testing solutions were simulated body fluids (SBF) and NaCl 0.9%. As stability experiments, cyclic voltammetry was performed and ions release was measured. The quantity of released cations in time as a kinetic aspect of passive stratum behavior was followed with an inductively coupled plasma mass spectrometer (ICP-MS) and apatite forming in SBF was found with infrared spectra. This study led to a comparison between the modification and the behavior of passive stratum on nanotubes as a function of their diameters.

Coordinate expression of cytokeratins 7 and 14, vimentin, and Bcl-2 in canine cutaneous epithelial tumors and cysts.

PubMed

Pieper, Jason B; Stern, Adam W; LeClerc, Suzette M; Campbell, Karen L

2015-07-01

Forty-seven canine cutaneous epithelial tumors and cysts were examined to determine coordinate expression of cytokeratins 7 (CK7) and 14 (CK14), vimentin, and Bcl-2 using commercially available antibodies. Within non-affected normal skin adjacent to tumors or cysts, CK7 expression was observed in luminal cells in apocrine glands; CK14 expression was observed in the stratum basale, stratum spinosum, stratum granulosum, basal layer of outer root sheath, sebaceous glands, and myoepithelial cells of apocrine glands; vimentin expression was observed in dermal papilla and scattered non-epithelial cells within the epidermis; and Bcl-2 expression was observed in scattered non-epithelial cells in the epidermis and some apocrine glands. The pattern of expression of CK7 and CK14 in cases of adenocarcinoma of the apocrine gland of the anal sac (CK7+/CK14-) and hepatoid gland tumors (CK7-/CK14+) may prove useful for diagnostic purposes. Loss of expression of CK14 and vimentin, identifying myoepithelial cells, was observed in apocrine and ceruminous adenocarcinomas. Differences in patterns of expression of Bcl-2 were observed between infundibular keratinizing acanthomas compared to trichoepitheliomas. © 2015 The Author(s).

Determination of the thickness and structure of the skin barrier by in vivo laser scanning microscopy

NASA Astrophysics Data System (ADS)

Lademann, J.; Richter, H.; Astner, S.; Patzelt, A.; Knorr, F.; Sterry, W.; Antoniou, Ch

2008-04-01

Normal skin barrier function is an essential aspect of skin homeostasis and regeneration. Dynamic inflammatory, proliferative and neoplastic skin processes such as wound healing, psoriasis and contact dermatitis are associated with a significant disruption of the skin barrier. In recent years, there has been increasing interest in evaluating cosmetic and pharmacologic products for their ability to restore these protective properties. The gold standard for characterization of barrier function has been the measurement of the transepidermal water loss, however the disadvantage of this method is its interference with several endogenous and exogenous factors such as hydration, perspiration and topically applied substances. This study was aimed to test the clinical applicability of a fluorescence confocal laser scanning microscope (LSM) for a systematic morphologic analysis of the structure, integrity and thickness of the stratum corneum in 10 otherwise healthy volunteers. The influence of skin treatment with commercial moisturizing cream on skin barrier function was evaluated in serial non-invasive examinations. Our findings showed that in vivo LSM may represent a simple and efficient method for the characterization of skin barrier properties, such as the thickness and hydration of the stratum corneum.

Biophysical effects of repetitive removal of adhesive dressings on peri-ulcer skin.

PubMed

Zillmer, R; Agren, M S; Gottrup, F; Karlsmark, T

2006-05-01

To study the effect of repeated removal of four different adhesive dressings on peri-ulcer skin using quantitative non-invasive techniques. Forty-five patients with open (n = 29) or healed (n = 16) venous leg ulcers were included. Peri-ulcer skin was treated for 14 days with patches of two different hydrocolloid-based adhesive dressings, one polyurethane adhesive and one soft silicone adhesive dressing. Normal skin of the patients' ventral forearm was also treated identically. Adhesive patches of the dressings were replaced every second day. The skin barrier function was assessed by measuring transepidermal water loss and stratum corneum hydration by measuring electrical conductance. Thirty-nine patients completed the study. The hydrocolloid adhesives increased transepidermal water loss and conductance while the polyurethane and soft silicone adhesives did not influence these parameters significantly compared with adjacent non-treated peri-ulcer skin. For normal forearm skin, similar relative effects among the four adhesives were found. Repetitive treatment with hydrocolloid-based adhesive dressings induced major functional alterations of the stratum corneum. In contrast, a polyurethane adhesive and a soft silicone adhesive dressing did not alter transepidermal water loss or conductance of peri-ulcer skin.

Reflectance spectroscopy can quantify cutaneous haemoglobin oxygenation by oxygen uptake from the atmosphere after epidermal barrier disruption.

PubMed

Heise, H M; Lampen, P; Stücker, M

2003-11-01

The supply of oxygen to the viable skin tissue within the upper layers is not only secured by the cutaneous blood vascular system, but to a significant part also by oxygen diffusion from the atmosphere through the horny layer. The aim of this study was to examine whether changes in haemoglobin oxygenation can be observed within the isolated perfused bovine udder skin used as a skin model by removing the upper horny layer by adhesive tape stripping. Diffuse reflectance spectroscopy in the visible spectral range was used for non-invasive characterisation of haemoglobin oxygenation in skin under in vitro conditions. Mid-infrared attenuated total reflectance spectroscopy was employed for analysing the surface layer of the stratum corneum with respect to keratin, water and lipid components. Skin barrier disruption was achieved by repeated stripping of superficial corneocyte layers by adhesive tape. Significant changes in skin haemoglobin oxygenation were observed for skin areas with reduced lipid concentration and a reduced stratum corneum layer, as determined from the quantitative evaluation of the diffuse reflectance skin spectra. The result can be interpreted as an increase of oxygen diffusion after the removal of the upper horny layer.

Thermal phase transition behavior of lipid layers on a single human corneocyte cell.

PubMed

Imai, Tomohiro; Nakazawa, Hiromitsu; Kato, Satoru

2013-09-01

We have improved the selected area electron diffraction method to analyze the dynamic structural change in a single corneocyte cell non-invasively stripped off from human skin surface. The improved method made it possible to obtain reliable diffraction images to trace the structural change in the intercellular lipid layers on a single corneocyte cell during heating from 24°C to 100°C. Comparison of the results with those of synchrotron X-ray diffraction experiments on human stratum corneum sheets revealed that the intercellular lipid layers on a corneocyte cell exhibit essentially the same thermal phase transitions as those in a stratum corneum sheet. These results suggest that the structural features of the lipid layers are well preserved after the mechanical stripping of the corneocyte cell. Moreover, electron diffraction analyses of the thermal phase transition behaviors of the corneocyte cells that had the lipid layers with different distributions of orthorhombic and hexagonal domains at 24°C suggested that small orthorhombic domains interconnected with surrounding hexagonal domains transforms in a continuous manner into new hexagonal domains. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Polymeric films loaded with vitamin E and aloe vera for topical application in the treatment of burn wounds.

PubMed

Pereira, Gabriela Garrastazu; Guterres, Sílvia Stanisçuaki; Balducci, Anna Giulia; Colombo, Paolo; Sonvico, Fabio

2014-01-01

Burns are serious traumas related to skin damage, causing extreme pain and possibly death. Natural drugs such as Aloe vera and vitamin E have been demonstrated to be beneficial in formulations for wound healing. The aim of this work is to develop and evaluate polymeric films containing Aloe vera and vitamin E to treat wounds caused by burns. Polymeric films containing different quantities of sodium alginate and polyvinyl alcohol (PVA) were characterized for their mechanical properties and drug release. The polymeric films, which were produced, were thin, flexible, resistant, and suitable for application on damaged skin, such as in burn wounds. Around 30% of vitamin E acetate was released from the polymeric films within 12 hours. The in vivo experiments with tape stripping indicated an effective accumulation in the stratum corneum when compared to a commercial cream containing the same quantity of vitamin E acetate. Vitamin E acetate was found in higher quantities in the deep layers of the stratum corneum when the film formulation was applied. The results obtained show that the bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of burns.

Recent Advances in Skin Penetration Enhancers for Transdermal Gene and Drug Delivery.

PubMed

Amjadi, Morteza; Mostaghaci, Babak; Sitti, Metin

2017-01-01

There is a growing interest in transdermal delivery systems because of their noninvasive, targeted, and on-demand delivery of gene and drugs. However, efficient penetration of therapeutic compounds into the skin is still challenging largely due to the impermeability of the outermost layer of the skin, known as stratum corneum. Recently, there have been major research activities to enhance the skin penetration depth of pharmacological agents. This article reviews recent advances in the development of various strategies for skin penetration enhancement. We show that approaches such as ultrasound waves, laser, and microneedle patches have successfully been employed to physically disrupt the stratum corneum structure for enhanced transdermal delivery. Rather than physical approaches, several non-physical route have also been utilized for efficient transdermal delivery across the skin barrier. Finally, we discuss some clinical applications of transdermal delivery systems for gene and drug delivery. This paper shows that transdermal delivery devices can potentially function for diverse healthcare and medical applications while further investigations are still necessary for more efficient skin penetration of gene and drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Polymeric Films Loaded with Vitamin E and Aloe vera for Topical Application in the Treatment of Burn Wounds

PubMed Central

Pereira, Gabriela Garrastazu; Guterres, Sílvia Stanisçuaki; Balducci, Anna Giulia; Colombo, Paolo

2014-01-01

Burns are serious traumas related to skin damage, causing extreme pain and possibly death. Natural drugs such as Aloe vera and vitamin E have been demonstrated to be beneficial in formulations for wound healing. The aim of this work is to develop and evaluate polymeric films containing Aloe vera and vitamin E to treat wounds caused by burns. Polymeric films containing different quantities of sodium alginate and polyvinyl alcohol (PVA) were characterized for their mechanical properties and drug release. The polymeric films, which were produced, were thin, flexible, resistant, and suitable for application on damaged skin, such as in burn wounds. Around 30% of vitamin E acetate was released from the polymeric films within 12 hours. The in vivo experiments with tape stripping indicated an effective accumulation in the stratum corneum when compared to a commercial cream containing the same quantity of vitamin E acetate. Vitamin E acetate was found in higher quantities in the deep layers of the stratum corneum when the film formulation was applied. The results obtained show that the bioadhesive films containing vitamin E acetate and Aloe vera could be an innovative therapeutic system for the treatment of burns. PMID:24524083

Transdermal transport pathway creation: Electroporation pulse order.

PubMed

Becker, Sid; Zorec, Barbara; Miklavčič, Damijan; Pavšelj, Nataša

2014-11-01

In this study we consider the physics underlying electroporation which is administered to skin in order to radically increase transdermal drug delivery. The method involves the application of intense electric fields to alter the structure of the impermeable outer layer, the stratum corneum. A generally held view in the field of skin electroporation is that the skin's drop in resistance (to transport) is proportional to the total power of the pulses (which may be inferred by the number of pulses administered). Contrary to this belief, experiments conducted in this study show that the application of high voltage pulses prior to the application of low voltage pulses result in lower transport than when low voltage pulses alone are applied (when less total pulse power is administered). In order to reconcile these unexpected experimental results, a computational model is used to conduct an analysis which shows that the high density distribution of very small aqueous pathways through the stratum corneum associated with high voltage pulses is detrimental to the evolution of larger pathways that are associated with low voltage pulses. Copyright © 2014 Elsevier Inc. All rights reserved.

Novel drug delivery strategies for porphyrins and porphyrin precursors

NASA Astrophysics Data System (ADS)

Morrow, D. I. J.; Donnelly, R. F.

2009-06-01

superficial lesions, such as actinic keratosis. In addition, photodynamic antimicrobial chemotherapy (PACT) is attracting increasing interest for the treatment of infection. However, delivery strategies for topical PDT and PACT are still based on application of rather simplistic cream and solution formulations, with little consideration given to thermodynamics, targeting or the physicochemical properties of the active agent. Purpose-designed dosage forms for topical delivery of aminolevulinic acid or its esters include creams containing penetration enhancers and/or iron chelators, pressure sensitive patches and bioadhesive patches. Such systems aim to enhance drug delivery across the stratum corneum and keratinised debris overlying neoplastic lesions and improve subsequent protoporphyrin IX (PpIX) production. The alternative to using porphyrin precursors is the use of pre-formed photosensitisers. However, owing to their relatively high molecular weights, conventional topical application is not appropriate. Innovative strategies, such as the use of needle-free injections and microneedle arrays, bypass the stratum corneum, enabling rapid and targeted delivery not only porphyrin precursors but also pre-formed photosensitisers. This presentation will review drug delivery work published to date in the fields of PDT and PACT. In addition, the benefits of employing the latest advances in pharmaceutical technology will be highlighted.

Large-scale human skin lipidomics by quantitative, high-throughput shotgun mass spectrometry.

PubMed

Sadowski, Tomasz; Klose, Christian; Gerl, Mathias J; Wójcik-Maciejewicz, Anna; Herzog, Ronny; Simons, Kai; Reich, Adam; Surma, Michal A

2017-03-07

The lipid composition of human skin is essential for its function; however the simultaneous quantification of a wide range of stratum corneum (SC) and sebaceous lipids is not trivial. We developed and validated a quantitative high-throughput shotgun mass spectrometry-based platform for lipid analysis of tape-stripped SC skin samples. It features coverage of 16 lipid classes; total quantification to the level of individual lipid molecules; high reproducibility and high-throughput capabilities. With this method we conducted a large lipidomic survey of 268 human SC samples, where we investigated the relationship between sampling depth and lipid composition, lipidome variability in samples from 14 different sampling sites on the human body and finally, we assessed the impact of age and sex on lipidome variability in 104 healthy subjects. We found sebaceous lipids to constitute an abundant component of the SC lipidome as they diffuse into the topmost SC layers forming a gradient. Lipidomic variability with respect to sampling depth, site and subject is considerable, and mainly accredited to sebaceous lipids, while stratum corneum lipids vary less. This stresses the importance of sampling design and the role of sebaceous lipids in skin studies.

Development of biodegradable hyperbranched core-multishell nanocarriers for efficient topical drug delivery.

PubMed

Du, Fang; Hönzke, Stefan; Neumann, Falko; Keilitz, Juliane; Chen, Wei; Ma, Nan; Hedtrich, Sarah; Haag, Rainer

2016-11-28

The topical application of drugs allows for a local application in skin disease and can reduce side effects. Here we present biodegradable core-multishell (CMS) nanocarriers which are composed of a hyperbranched polyglycerol core functionalized with diblock copolymers consisting of polycaprolactone (PCL) and poly(ethylene glycol) (mPEG) as the outer shell. The anti-inflammatory drug Dexamethasone (Dexa) was loaded into these CMS nanocarriers. DLS results suggested that Dexa loaded nanoparticles mostly act as a unimolecular carrier system. With longer PCL segments, a better transport capacity is observed. In vitro skin permeation studies showed that CMS nanocarriers could improve the Nile red penetration through the skin by up to 7 times, compared to a conventional cream formulation. Interestingly, covalently FITC-labeled CMS nanocarriers remain in the stratum corneum layer. This suggests the enhancement is due to the release of cargo after being transported into the stratum corneum by the CMS nanocarriers. In addition, the hPG-PCL-mPEG CMS nanocarriers exhibited good stability, low cytotoxicity, and their production can easily be scaled up, which makes them promising nanocarriers for topical drug delivery. Copyright © 2016 Elsevier B.V. All rights reserved.

Rapid fabrication method of a microneedle mold with controllable needle height and width.

PubMed

Lin, Yen-Heng; Lee, I-Chi; Hsu, Wei-Chieh; Hsu, Ching-Hong; Chang, Kai-Ping; Gao, Shao-Syuan

2016-10-01

The main issue of transdermal drug delivery is that macromolecular drugs cannot diffuse through the stratum corneum of skin. Many studies have pursued micro-sized needles encapsulated with drugs to overcome this problem, as these needles can pierce the stratum corneum and allow drugs to enter the circulatory system of the human body. However, most microneedle fabrication processes are time-consuming and require expensive equipment. In this study, we demonstrate a rapid method for fabricating a microneedle mold using drawing lithography and a UV-cured resin. The mold was filled with a water-soluble material, polyvinylpyrrolidone (PVP), which was then demolded to produce a water-soluble microneedle array. The results of an in vitro skin insertion test using PVP microneedles and pig ear skin demonstrated the feasibility of the microneedle mold. In addition, by controlling the viscosity of the UV-cured resin through various heat treatments, microneedles with different heights and aspect ratios were produced. Compared with other methods, this technology significantly simplifies and accelerates the mold fabrication process. In addition, the required equipment is relatively simple and inexpensive. Through this technology, we can rapidly fabricate microneedle molds with controllable dimensions for various applications.

Leaf epidermis images for robust identification of plants

PubMed Central

da Silva, Núbia Rosa; Oliveira, Marcos William da Silva; Filho, Humberto Antunes de Almeida; Pinheiro, Luiz Felipe Souza; Rossatto, Davi Rodrigo; Kolb, Rosana Marta; Bruno, Odemir Martinez

2016-01-01

This paper proposes a methodology for plant analysis and identification based on extracting texture features from microscopic images of leaf epidermis. All the experiments were carried out using 32 plant species with 309 epidermal samples captured by an optical microscope coupled to a digital camera. The results of the computational methods using texture features were compared to the conventional approach, where quantitative measurements of stomatal traits (density, length and width) were manually obtained. Epidermis image classification using texture has achieved a success rate of over 96%, while success rate was around 60% for quantitative measurements taken manually. Furthermore, we verified the robustness of our method accounting for natural phenotypic plasticity of stomata, analysing samples from the same species grown in different environments. Texture methods were robust even when considering phenotypic plasticity of stomatal traits with a decrease of 20% in the success rate, as quantitative measurements proved to be fully sensitive with a decrease of 77%. Results from the comparison between the computational approach and the conventional quantitative measurements lead us to discover how computational systems are advantageous and promising in terms of solving problems related to Botany, such as species identification. PMID:27217018

Chronic dermatophytosis: what is special about Trichophyton rubrum?

PubMed

Dahl, M V; Grando, S A

1994-01-01

T. rubrum is especially suited to survive on the skin surface. We have presented data to show how it accomplishes this. We will now combine these data with our own thoughts to speculate about how T. rubrum has adapted to the skin of human beings. We believe the organism uses several different strategies. First, many infected patients cannot elicit a cell-mediated immune response to eliminate the fungus. The reasons for this are not completely clear, but trichophytin skin tests are negative at 48 hours despite persistent, chronic, and even widespread infections. Antigens are present on T. rubrum, just as they are on other dermatophytes, but differences in antigen penetration through the skin may prevent induction of immunity. Perhaps, neonatal exposure to the fungus or to cross-reacting antigens of molds may induce tolerance by confusing antigen recognition of self vs. nonself. More likely, persistent infection induces immunologic unresponsiveness by activating specific suppressor T cells. In fact, our attempts to clone T. rubrum-specific T cells from peripherals blood have always yielded suppressor cells, and these cells even suppress proliferation of the clone itself. Second, mannans from T. rubrum probably are better able to suppress cell-mediated immune reactions than are mannans from other fungi. T. rubrum may make more mannan than do other dermatophytes, and the mannan may be a more potent immunosuppressor than are mannans from other dermatophytes. Mannan apparently works by inhibiting critical steps in antigen processing or presentation. This inhibits the immune reaction. Perhaps, mannan even can prevent induction under certain circumstances. Third, T. rubrum is not especially aggressive compared with other dermatophytes. By remaining in the stratum corneum, it may evade immune surveillance, and may evade complement and polymorphonuclear leukocytes that would attach the organism if it tried to invade into viable epidermis. Finally, T. rubrum can survive off

Optimization, validation and application of headspace solid-phase microextraction gas chromatography for the determination of 1-nitro-2-phenylethane and methyleugenol from Aniba canelilla (H.B.K.) Mez essential oil in skin permeation samples.

PubMed

Kreutz, Tainá; Lucca, Letícia G; Loureiro-Paes, Orlando A R; Teixeira, Helder F; Veiga, Valdir F; Limberger, Renata P; Ortega, George G; Koester, Letícia S

2018-06-02

Aniba canelilla (H.B.K.) Mez is an aromatic plant from the Amazon region whose essential oil has 1-nitro-2-phenylethane (NP) and methyleugenol (ME) as major compounds. Despite of the scientifically proven antifungal and anti-inflammatory activities for these compounds, there is no report up to date about the topical permeation or quantification of NP and ME on skin samples. The aim of this study was the validation of an optimized bioanalytical method by solid-phase microextraction in headspace mode in gas chromatograph with flame ionization detector (HS-SPME-GC-FID) for the determination of NP and ME from the oil in different samples from permeation study, such as porcine ear skin (PES) layers (stratum corneum, epidermis and dermis) and receptor fluid (RF). For this propose polydimethylsiloxane fibers (100 μm) were used and HS-SPME extraction condition consisted of 53 °C, 21 min, and 5% w.v -1 NaCl addition. The wide range of the calibration curve (2.08-207.87 μg mL -1 for NP and 0.40-40.41 μg mL -1 for ME), the presence of matrix interferences and the intrinsic characteristics of HS-SPME required a data linearization using Log 10 . Thereby, data and the gained results presented homoscedasticity, normalization of residues and adequate linearity (r 2  > 0.99) and accuracy for both compounds. In order to verify the applicability of the validated method, the HS-SPME-GC-FID procedure was performed to determine the amount of NP and ME permeated and retained in samples after Franz diffusion cell study from different dosages (20, 100 and 200 μL) of A. canelilla oil. Compounds permeation showed a progressive increase and penetration dependence based on the dosage applied. Furthermore, retention was in order receptor fluid > dermis > epidermis > stratum corneum for both compounds, suggesting NP and ME could penetrate deep tissue, probably due to the partition coefficient, mass, size, and solubility of these compounds. In conclusion, the

Regeneration of the epidermis and basement membrane of the planarian Dugesia japonica after total-body x irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hori, I.

1979-03-01

Fresh-water planarians were studied to examine effects of x rays on regeneration of the epidermis and basement membrane. During early stages of regeneration, free rhabdite-forming cells were associated with the wound epidermis and recruited it. In later stages, however, a gradual degeneration occurred in the epidermis and cells undergoing epithelization decreased in number. Eventually epidermal cells on the wound surface appeared necrotic as evidenced by pyknotic nuclei and vacuolized dense cytoplasm. The entire basement membrane could not be reconstituted in any stage after wounding though its precursor-like material was secreted in the interspace between epidermis and parenchyma. Morphological changes inmore » extracellular products and in the cells surrounding the products suggest that epidermal cells which have covered the wound surface synthesize precursors of the basement membrane. Possible factors of a characteristic perturbation in epithelization and basement membrane formation after total-body irradiation are discussed.« less

Mitotic activity in dorsal epidermis of Rana pipiens.

NASA Technical Reports Server (NTRS)

Garcia-Arce, H.; Mizell, S.

1972-01-01

Study of statistically significant rhythms of mitotic division in dorsal epidermis of frogs, Rana pipiens, exposed to a 12:12 light:dark environment for 14 days. The results include the findings that (1) male animals have a primary period of 22 hr in summer and 18 hr in winter, (2) female animals have an 18 hr period, and (3) parapinealectomy and blinding abolish the rhythm.

Nuclear localization of activated STAT6 and STAT3 in epidermis of prurigo nodularis.

PubMed

Fukushi, S; Yamasaki, K; Aiba, S

2011-11-01

Prurigo nodularis (PN) is a chronic dermatitis characterized by discrete, raised, and firm papulonodules with intense pruritus. The pathogenesis still remains to be elucidated. To clarify the role of Th1 and Th2 cytokines in the pathogenesis of PN. We examined the cytokine signatures, such as phosphorylation of STAT1, STAT3 and STAT6, HLA-DR and hyaluronan accumulation, to reveal the Th1 and Th2 cytokine influence on the lesional epidermis of PN. We first optimized antigen retrieval methods to detect these signatures with antibodies for phospho-STAT1 (pSTAT1), phospho-STAT3 (pSTAT3), phospho-STAT6 (pSTAT6), HLA-DR and hyaluronic acid binding protein (HABP) on the formalin-fixed paraffin-embedded sections of psoriasis, lichen planus and atopic dermatitis biopsy samples. Activation of STAT1 and STAT6 in epidermis by Th1 and Th2 cytokines was further confirmed in a cultured skin equivalent model treated with interferon-γ or interleukin (IL)-4/IL-13. With the relevant immunostaining methods, we examined the cytokine signatures in 22 cases of PN. The results revealed that (i) the entire epidermis of 19 cases was stained with anti-pSTAT6 antibody, (ii) 21 cases demonstrated nuclear staining with anti-pSTAT3 antibody, (iii) the entire epidermis of 21 cases was stained with HABP, (iv) the epidermis of eight cases showed scattered staining with anti-pSTAT1 antibody, and (v) six cases were positive for HLA-DR membrane expression. These data indicated that Th2 cytokines related to STAT6 activation together with some unknown stimuli that activate STAT3 play a principal role in the pathogenesis of PN. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.

Immunocytochemical and autoradiographic studies on the process of keratinization in avian epidermis suggests absence of keratohyalin.

PubMed

Alibardi, Lorenzo

2004-02-01

The process of keratinization in apteric avian epidermis and in scutate scales of some avian species has been studied by autoradiography for histidine and immunohistochemistry for keratins and other epidermal proteins. Acidic or basic alpha-keratins are present in basal, spinosus, and transitional layers, but are not seen in the corneous layer. Keratinization-specific alpha-keratins (AE2-positive) are observed in the corneous layer of apteric epidermis but not in that of scutate scales, which contain mainly beta-keratin. Alpha-keratin bundles accumulate along the plasma membrane of transitional cells of apteric epidermis. In contrast to the situation in scutate scales, in the transitional layer and in the lowermost part of the corneous layer of apteric epidermis, filaggrin-like, loricrin-like, and transglutaminase immunoreactivities are present. The lack of isopeptide bond immunoreactivity suggests that undetectable isopeptide bonds are present in avian keratinocytes. Using immunogold ultrastructural immunocytochemistry a low but localized loricrin-like and, less, filaggrin-like labeling is seen over round-oval granules or vesicles among keratin bundles of upper spinosus and transitional keratinocytes of apteric epidermis. Filaggrin-and loricrin-labeling are absent in alpha-keratin bundles localized along the plasma membrane and in the corneous layer, formerly considered keratohyalin. Using ultrastructural autoradiography for tritiated histidine, occasional trace grains are seen among these alpha-keratin bundles. A different mechanism of redistribution of matrix and corneous cell envelope proteins probably operates in avian keratinocytes as compared to that of mammals. Keratin bundles are compacted around the lipid-core of apteric epidermis keratinocytes, which do not form complex chemico/mechanical-resistant corneous cell envelopes as in mammalian keratinocytes. These observations suggest that low amounts of matrix proteins are present among keratin bundles of

Development of a Rat Model to Investigate Contributions of Anatomic and Physiologic Determinants of in Vivo Skin Permeation

DTIC Science & Technology

1991-08-30

physiologic states. Physiologic perturbations were performed to test the sensitivity of the model system to detect effects of minoxidil -mediated... Minoxidil , leukotriene D̂ , tape stripping of stratum corneum, and topical ether-ethanol experiments produced statistically significant increases (52 to... Minoxidil 68 B. Phenylephrine 69 C. Leukotriene D̂ 69 D. Ether-Ethanol 70 E. Tape stripping 76 8. Data analysis 77 Vlll RESULTS 80 1

Lack of Effect of 94 GHz Radio Frequency Radiation Exposure in an Animal Model of Skin Carcinogenesis

DTIC Science & Technology

2001-10-01

villous or arborescent outgrowths of fibrovascular stroma covered by neoplastic cells; although benign, papillomas are premalignant lesions that will...thin stratum corneum; 1, minimal hyperplasia , epithelium ~4–6 cell layers thick; 2, minimal to mild hyperplasia , variable amounts of hyperplasia ...across the specimen, areas fitting each description present; 3, mild hyperplasia , epithelium ~7–9 cell layers thick or epithelial layer composed of ~4–6

The expression and regulation of enzymes mediating the biosynthesis of triglycerides and phospholipids in keratinocytes/epidermis

PubMed Central

Feingold, Kenneth R

2011-01-01

Triglycerides and phospholipids play an important role in epidermal permability barrier formation and function. They are synthesized de novo in the epidermis via the glycerol-3-phosphate pathway, catalyzed sequentially by a group of enzymes that have multiple isoforms including glycerol-3-phosphate acyltransferase (GPAT), 1-acylglycerol-3-phosphate acyltransferase (AGPAT), Lipin and diacylglycerol acyltransferase (DGAT). Here we review the current knowledge of GPAT, AGPAT, Lipin and DGAT enzymes in keratinocytes/epidermis focusing on the expression levels of the various isoforms and their localization in mouse epidermis. Additionally, the factors regulating their gene expression, including calcium induced differentiation, PPAR and LXR activators, and the effect of acute permeability barrier disruption will be discussed. PMID:21695015

Emotional intelligence is a second-stratum factor of intelligence: evidence from hierarchical and bifactor models.

PubMed

MacCann, Carolyn; Joseph, Dana L; Newman, Daniel A; Roberts, Richard D

2014-04-01

This article examines the status of emotional intelligence (EI) within the structure of human cognitive abilities. To evaluate whether EI is a 2nd-stratum factor of intelligence, data were fit to a series of structural models involving 3 indicators each for fluid intelligence, crystallized intelligence, quantitative reasoning, visual processing, and broad retrieval ability, as well as 2 indicators each for emotion perception, emotion understanding, and emotion management. Unidimensional, multidimensional, hierarchical, and bifactor solutions were estimated in a sample of 688 college and community college students. Results suggest adequate fit for 2 models: (a) an oblique 8-factor model (with 5 traditional cognitive ability factors and 3 EI factors) and (b) a hierarchical solution (with cognitive g at the highest level and EI representing a 2nd-stratum factor that loads onto g at λ = .80). The acceptable relative fit of the hierarchical model confirms the notion that EI is a group factor of cognitive ability, marking the expression of intelligence in the emotion domain. The discussion proposes a possible expansion of Cattell-Horn-Carroll theory to include EI as a 2nd-stratum factor of similar standing to factors such as fluid intelligence and visual processing.

Novel hydrogel-based preparation-free EEG electrode.

PubMed

Alba, Nicolas Alexander; Sclabassi, Robert J; Sun, Mingui; Cui, Xinyan Tracy

2010-08-01

The largest obstacles to signal transduction for electroencephalography (EEG) recording are the hair and the epidermal stratum corneum of the skin. In typical clinical situations, hair is parted or removed, and the stratum corneum is either abraded or punctured using invasive penetration devices. These steps increase preparation time, discomfort, and the risk of infection. Cross-linked sodium polyacrylate gel swelled with electrolyte was explored as a possible skin contact element for a prototype preparation-free EEG electrode. As a superabsorbent hydrogel, polyacrylate can swell with electrolyte solution to a degree far beyond typical contemporary electrode materials, delivering a strong hydrating effect to the skin surface. This hydrating power allows the material to increase the effective skin contact surface area through wetting, and noninvasively decrease or bypass the highly resistive barrier of the stratum corneum, allowing for reduced impedance and improved electrode performance. For the purposes of the tests performed in this study, the polyacrylate was prepared both as a solid elastic gel and as a flowable paste designed to penetrate dense scalp hair. The gel can hold 99.2% DI water or 91% electrolyte solution, and the water content remains high after 29 h of air exposure. The electrical impedance of the gel electrode on unprepared human forearm is significantly lower than a number of commercial ECG and EEG electrodes. This low impedance was maintained for at least 8 h (the longest time period measured). When a paste form of the electrode was applied directly onto scalp hair, the impedance was found to be lower than that measured with commercially available EEG paste applied in the same manner. Time-frequency transformation analysis of frontal lobe EEG recordings indicated comparable frequency response between the polyacrylate-based electrode on unprepared skin and the commercial EEG electrode on abraded skin. Evoked potential recordings demonstrated

Effects of a Skin Barrier Cream on Management of Incontinence-Associated Dermatitis in Older Women: A Cluster Randomized Controlled Trial.

PubMed

Kon, Yuka; Ichikawa-Shigeta, Yoshie; Iuchi, Terumi; Nakajima, Yukari; Nakagami, Gojiro; Tabata, Keiko; Sanada, Hiromi; Sugama, Junko

The purpose of this study was to examine the effects of a skin barrier cream with moisturization and skin-protectant characteristics for improving the severity of incontinence-associated dermatitis (IAD) pertaining to the skin physiology and appearance. We measured the following outcomes: (1) skin physiological characteristics indicating skin protection and enhancement of the skin's moisture barrier (stratum corneum hydration, dermis hydration level, transepidermal water loss, and skin pH); and (2) changes in skin appearance (the degree of erythema and pigmentation, and the sulcus cutis condition). Single-blind, cluster randomized controlled trial. The study was conducted in a long-term care facility in Japan between November 7, 2011, and May 6, 2012. We used block randomization to obtain a random sample of 6 (4 experimental and 2 control) out of 10 available wards. All subjects were elderly women with IAD of the buttock or inner thigh. We assessed 295 patients, but only 33 met inclusion criteria; 18 were allocated to the experimental group and 15 were allocated to the control group. All participants were managed with cleansing with a skin cleanser and application of a moisturizer daily. In addition, a skin barrier cream designed to enhance the skin's moisture barrier and act as a protective barrier was applied to the skin of patients in the experimental group 3 times a day when absorptive briefs were changed. Skin physiological and appearance characteristics were scored only at the buttock or thigh area. All data were collected on days 1 and 14 of the study. Univariate analysis found that the erythema index was lower in the intervention group than in the control group at day 14 (P = .004). Multivariate analysis found significant associations between use of the skin barrier cream and increased stratum corneum hydration (β= .443, P = .031), decreased skin pH (β=-.439, P = .020), and magnitude of erythema (β=-.451, P = .018). Study findings suggest that a barrier

Stratum corneum integrity as a predictor for peristomal skin problems in ostomates.

PubMed

Nybaek, H; Lophagen, S; Karlsmark, T; Bang Knudsen, D; Jemec, G B E

2010-02-01

Peristomal skin problems are common, most often the result is disruption of the skin barrier and this may account for more than one in three visits to ostomy nurses. Therefore a specific assessment of individual risk factors relating to the skin barrier function would be of great interest. Skin barrier integrity in ostomy patients with peristomal skin problems (PSP) was compared with that of ostomy patients with normal skin (controls) using transepidermal water loss (TEWL). Mechanical barrier disruption was determined by a tape stripping test and chemical barrier disruption [sodium lauryl sulphate (SLS) 0.25%]. Patients and controls had a highly significant increase in TEWL value in the peristomal area compared with nonperistomal contralateral abdominal skin (P < 0.0001 for both groups). The skin barrier of normal-looking contralateral skin of ostomates was found to be borderline impaired in patients with PSP compared with those without. A linear association was seen between the number of tape strips removed and TEWL for both cases and controls. Tape stripping suggested that patients with PSP had less resilient skin (P = 0.002). A significant difference in TEWL value between cases and controls was also seen for the SLS patch test on the dorsal skin (P = 0.02). Successive tape stripping, a situation analogous to the normal use of a pouching system, caused a higher degree of barrier damage more rapidly in patients with PSP, indicating an impaired mechanical quality of the barrier. The SLS exposure test suggested a generally increased susceptibility to irritant dermatitis as assessed by TEWL. Our findings suggest tape stripping and SLS testing may have a role as predictive tests to identify patients at risk of PSP.

DEFECTIVE KERNEL1 (DEK1) Regulates Cell Walls in the Leaf Epidermis1

PubMed Central

Amanda, Dhika; Ingram, Gwyneth C.

2016-01-01

The plant epidermis is crucial to survival, regulating interactions with the environment and controlling plant growth. The phytocalpain DEFECTIVE KERNEL1 (DEK1) is a master regulator of epidermal differentiation and maintenance, acting upstream of epidermis-specific transcription factors, and is required for correct cell adhesion. It is currently unclear how changes in DEK1 lead to cellular defects in the epidermis and the pathways through which DEK1 acts. We have combined growth kinematic studies, cell wall analysis, and transcriptional analysis of genes downstream of DEK1 to determine the cause of phenotypic changes observed in DEK1-modulated lines of Arabidopsis (Arabidopsis thaliana). We reveal a novel role for DEK1 in the regulation of leaf epidermal cell wall structure. Lines with altered DEK1 activity have epidermis-specific changes in the thickness and polysaccharide composition of cell walls that likely underlie the loss of adhesion between epidermal cells in plants with reduced levels of DEK1 and changes in leaf shape and size in plants constitutively overexpressing the active CALPAIN domain of DEK1. Calpain-overexpressing plants also have increased levels of cellulose and pectins in epidermal cell walls, and this is correlated with the expression of several cell wall-related genes, linking transcriptional regulation downstream of DEK1 with cellular effects. These findings significantly advance our understanding of the role of the epidermal cell walls in growth regulation and establish a new role for DEK1 in pathways regulating epidermal cell wall deposition and remodeling. PMID:27756823

Prolonged viability of human organotypic skin explant in culture method (hOSEC)*

PubMed Central

Frade, Marco Andrey Cipriani; de Andrade, Thiago Antônio Moretti; Aguiar, Andréia Fernanda Carvalho Leone; Guedes, Flávia Araújo; Leite, Marcel Nani; Passos, Williane Rodrigues; Coelho, Eduardo Barbosa; Das, Pranab Kummar

2015-01-01

BACKGROUND: Currently, the cosmetic industry is overwhelmed in keeping up with the safety assessment of the increasing number of new products entering the market. To meet such demand, research centers have explored alternative methods to animal testing and also the large number of volunteers necessary for preclinical and clinical tests. OBJECTIVES: This work describes the human skin ex-vivo model (hOSEC: Human Organotypic Skin Explant Culture) as an alternative to test the effectiveness of cosmetics and demonstrate its viability through cutaneous keratinocytes' proliferative capacity up to 75 days in culture. METHODS: The skin explants obtained from surgeries were cultured in CO2-humid incubator. After 1, 7, 30 and 75 days in culture, skin fragments were harvested for analysis with histomorphological exam (HE staining) on all days of follow-up and immunohistochemistry for Ck5/6, Ck10 and Ki-67 only on the 75th day. RESULTS: On the 7th day, the epidermis was perfect in the dermoepidermal junction, showing the viability of the model. On the 30th day, the epidermis was thicker, with fewer layers on the stratum corneum, although the cutaneous structure was unaltered. On the 75th day, the skin became thinner but the dermoepidermal junctions were preserved and epidermal proliferation was maintained. After the 75th day on culture, the skin was similar to normal skin, expressing keratinocytes with Ck5/6 on supra-basal layers; Ck10 on differentiated layers; and viability could be assessed by the positivity of basal cells by Ki-67. CONCLUSION: The hOSEC model seems a good alternative to animal testing; it can be used as a preclinical test analogous to clinical human skin test with similar effectiveness and viability proven by immunohistological analyses. PMID:26131864

Functional respiratory morphology in the newborn quokka wallaby (Setonix brachyurus)

PubMed Central

Makanya, A N; Tschanz, S A; Haenni, B; Burri, P H

2007-01-01

A morphological and morphometric study of the lung of the newborn quokka wallaby (Setonix brachyurus) was undertaken to assess its morphofunctional status at birth. Additionally, skin structure and morphometry were investigated to assess the possibility of cutaneous gas exchange. The lung was at canalicular stage and comprised a few conducting airways and a parenchyma of thick-walled tubules lined by stretches of cuboidal pneumocytes alternating with squamous epithelium, with occasional portions of thin blood–gas barrier. The tubules were separated by abundant intertubular mesenchyme, aggregations of developing capillaries and mesenchymal cells. Conversion of the cuboidal pneumocytes to type I cells occurred through cell broadening and lamellar body extrusion. Superfluous cuboidal cells were lost through apoptosis and subsequent clearance by alveolar macrophages. The establishment of the thin blood–gas barrier was established through apposition of the incipient capillaries to the formative thin squamous epithelium. The absolute volume of the lung was 0.02 ± 0.001 cm3 with an air space surface area of 4.85 ± 0.43 cm2. Differentiated type I pneumocytes covered 78% of the tubular surface, the rest 22% going to long stretches of type II cells, their precursors or low cuboidal transitory cells with sparse lamellar bodies. The body weight-related diffusion capacity was 2.52 ± 0.56 mL O2 min−1 kg−1. The epidermis was poorly developed, and measured 29.97 ± 4.88 µm in thickness, 13% of which was taken by a thin layer of stratum corneum, measuring 4.87 ± 0.98 µm thick. Superficial capillaries were closely associated with the epidermis, showing the possibility that the skin also participated in some gaseous exchange. Qualitatively, the neonate quokka lung had the basic constituents for gas exchange but was quantitatively inadequate, implying the significance of percutaneous gas exchange. PMID:17553103

Prolonged viability of human organotypic skin explant in culture method (hOSEC).

PubMed

Frade, Marco Andrey Cipriani; Andrade, Thiago Antônio Moretti de; Aguiar, Andréia Fernanda Carvalho Leone; Guedes, Flávia Araújo; Leite, Marcel Nani; Passos, Williane Rodrigues; Coelho, Eduardo Barbosa; Das, Pranab Kummar

2015-01-01

Currently, the cosmetic industry is overwhelmed in keeping up with the safety assessment of the increasing number of new products entering the market. To meet such demand, research centers have explored alternative methods to animal testing and also the large number of volunteers necessary for preclinical and clinical tests. This work describes the human skin ex-vivo model (hOSEC: Human Organotypic Skin Explant Culture) as an alternative to test the effectiveness of cosmetics and demonstrate its viability through cutaneous keratinocytes' proliferative capacity up to 75 days in culture. The skin explants obtained from surgeries were cultured in CO2-humid incubator. After 1, 7, 30 and 75 days in culture, skin fragments were harvested for analysis with histomorphological exam (HE staining) on all days of follow-up and immunohistochemistry for Ck5/6, Ck10 and Ki-67 only on the 75th day. On the 7th day, the epidermis was perfect in the dermoepidermal junction, showing the viability of the model. On the 30th day, the epidermis was thicker, with fewer layers on the stratum corneum, although the cutaneous structure was unaltered. On the 75th day, the skin became thinner but the dermoepidermal junctions were preserved and epidermal proliferation was maintained. After the 75th day on culture, the skin was similar to normal skin, expressing keratinocytes with Ck5/6 on supra-basal layers; Ck10 on differentiated layers; and viability could be assessed by the positivity of basal cells by Ki-67. The hOSEC model seems a good alternative to animal testing; it can be used as a preclinical test analogous to clinical human skin test with similar effectiveness and viability proven by immunohistological analyses.

Morphology of the Epidermis of the Neotropical Catfish Pimelodella lateristriga (Lichtenstein, 1823) with Emphasis in Club Cells

PubMed Central

Damasceno, Eduardo Medeiros; Monteiro, Juliana Castro; Duboc, Luiz Fernando; Dolder, Heidi; Mancini, Karina

2012-01-01

The epidermis of Ostariophysi fish is composed of 4 main cell types: epidermal cells (or filament containing cells), mucous cells, granular cells and club cells. The morphological analysis of the epidermis of the catfish Pimelodella lateristriga revealed the presence of only two types of cells: epidermal and club cells. The latter were evident in the middle layer of the epidermis, being the largest cells within the epithelium. Few organelles were located in the perinuclear region, while the rest of the cytoplasm was filled with a non-vesicular fibrillar substance. Club cells contained two irregular nuclei with evident nucleoli and high compacted peripheral chromatin. Histochemical analysis detected prevalence of protein within the cytoplasm other than carbohydrates, which were absent. These characteristics are similar to those described to most Ostariophysi studied so far. On the other hand, the epidermal cells differ from what is found in the literature. The present study described three distinct types, as follows: superficial, abundant and dense cells. Differences among them were restricted to their cytoplasm and nucleus morphology. Mucous cells were found in all Ostariophysi studied so far, although they were absent in P. lateristriga, along with granular cells, also typical of other catfish epidermis. The preset study corroborates the observations on club cells' morphology in Siluriformes specimens, and shows important differences in epidermis composition and cell structure of P. lateristriga regarding the literature data. PMID:23226253

Robust control of mitotic spindle orientation in the developing epidermis

PubMed Central

Poulson, Nicholas D.

2010-01-01

Progenitor cells must balance self-amplification and production of differentiated progeny during development and homeostasis. In the epidermis, progenitors divide symmetrically to increase surface area and asymmetrically to promote stratification. In this study, we show that individual epidermal cells can undergo both types of division, and therefore, the balance is provided by the sum of individual cells’ choices. In addition, we define two control points for determining a cell’s mode of division. First is the expression of the mouse Inscuteable gene, which is sufficient to drive asymmetric cell division (ACD). However, there is robust control of division orientation as excessive ACDs are prevented by a change in the localization of NuMA, an effector of spindle orientation. Finally, we show that p63, a transcriptional regulator of stratification, does not control either of these processes. These data have uncovered two important regulatory points controlling ACD in the epidermis and allow a framework for analysis of how external cues control this important choice. PMID:21098114

Which Stratum of Urban Elderly Is Most Vulnerable for Dementia?

PubMed Central

2016-01-01

Many factors associated with a patient's lifestyle may disrupt timely access to dementia diagnosis and management. The aim of this study was to compare characteristics of lifestyle factors at the time of initial evaluation for dementia across degrees of dementia, and to identify risk factors relating to late detection of dementia, in order to understand the various lifestyle barriers to timely recognition of the disease. We reviewed medical records of 1,409 subjects who were diagnosed as dementia among 35,723 inhabitants of Gwangjin-gu. Dementia severity was divided into three degrees. Age, sex, education, income, smoking, heavy drinking, physical activity, religion, and living conditions were evaluated. There was a significantly greater proportion of individuals who were old age, female, less educated, who had never smoked or drank heavily, without physical activity, with no religious activity and living with family other than spouse in the severe dementia group. The lifestyle risks of late detection were old age, lower education, less social interactions, less physical activity or living with family. We can define this group of patients as the vulnerable stratum to dementia evaluation. Health policy or community health services might find ways to better engage patients in this vulnerable stratum to dementia. PMID:27550494

Interleukin-33 is expressed in the lesional epidermis in herpes virus infection but not in verruca vulgaris.

PubMed

Jin, Meijuan; Komine, Mayumi; Tsuda, Hidetoshi; Oshio, Tomoyuki; Ohtsuki, Mamitaro

2018-04-25

Interleukin (IL)-33 is released on cell injury and activates the immune reaction. IL-33 is involved in antiviral reaction in herpes virus infection, but the source that secretes IL-33 has not been identified. We speculate that keratinocytes injured in herpes virus infection secrete IL-33. In order to detect IL-33 in the lesional epidermis of patients with herpes virus infection, we immunostained several cutaneous herpes virus infection samples with an anti-IL-33 antibody, and compared them with cutaneous human papilloma virus (HPV) infection samples. We observed strong nuclear and mild cytoplasmic staining in epidermal keratinocytes of the lesional skin samples with herpes simplex virus and varicella zoster virus infections. However, staining was not observed in the epidermis of verruca vulgaris (VV) samples. We assumed that the strong immune reaction to herpes virus infection may depend on strong IL-33 expression in the epidermis, while very weak immune reaction in samples from patients with VV may be due to low or no expression of IL-33 in the lesional epidermis. © 2018 Japanese Dermatological Association.

Root growth regulation and gravitropism in maize roots does not require the epidermis

NASA Technical Reports Server (NTRS)

Bjorkman, T.; Cleland, R. E.

1991-01-01

We have earlier published observations showing that endogenous alterations in growth rate during gravitropism in maize roots (Zea mays L.) are unaffected by the orientation of cuts which remove epidermal and cortical tissue in the growing zone (Bjorkman and Cleland, 1988, Planta 176, 513-518). We concluded that the epidermis and cortex are not essential for transporting a growth-regulating signal in gravitropism or straight growth, nor for regulating the rate of tissue expansion. This conclusion has been challenged by Yang et al. (1990, Planta 180, 530-536), who contend that a shallow girdle around the entire perimeter of the root blocks gravitropic curvature and that this inhibition is the result of a requirement for epidermal cells to transport the growth-regulating signal. In this paper we demonstrate that the entire epidermis can be removed without blocking gravitropic curvature and show that the position of narrow girdles does not affect the location of curvature. We therefore conclude that the epidermis is not required for transport of a growth-regulating substance from the root cap to the growing zone, nor does it regulate the growth rate of the elongating zone of roots.

Skin penetration of silicon dioxide microneedle arrays.

PubMed

Kim, Sangchae; Shetty, S; Price, D; Bhansali, S

2006-01-01

Out-of-plane hollow silicon dioxide microneedle arrays were fabricated and investigated to determine their efficacy for transdermal applications. The fabrication process of the SiO2 microneedles is described, and mechanical fracture forces were investigated on microneedles with different geometrical dimensions. Biomechanical characterization of the microneedles was performed to specifically test for reliable stratum corneum and skin insertion by changing the regulatory parameters such as needle width and cross-section.

Progress in the use of microemulsions for transdermal and dermal drug delivery.

PubMed

Ita, Kevin

2017-06-01

Transdermal drug delivery continues to attract considerable interest in the scientific community. However, due to the hindrance provided by the stratum corneum, it is not possible to deliver most medications in therapeutically significant amounts. One of the ways of increasing the penetration of drugs across the skin is through the use of microemulsions (MEs). This review focuses on the role of MEs in enhancing topical and transdermal drug delivery.

Application of Gelidium corneum edible films containing carvacrol for ham packages.

PubMed

Lim, G O; Hong, Y H; Song, K B

2010-01-01

We prepared an edible film of Gelidium corneum (GC) containing carvacrol as an antimicrobial and antioxidative agent. The GC film containing carvacrol significantly decreased the WVP, while TS and %E values were increased, compared to the film without carvacrol. Increasing amounts of an antimicrobial agent increased antimicrobial activity against Escherichia coli O157:H7 and Listeria monocytogenes. Application of the film to ham packaging successfully inhibited the microbial growth and lipid oxidation of ham during storage. Our results indicate that GC film can be a useful edible packaging material for food products, and the incorporation of carvacrol in the GC film may extend the shelf life.

Diagnosis Applications of Non-Crystalline Diffraction of Collagen Fibres: Breast Cancer and Skin Diseases

NASA Astrophysics Data System (ADS)

Costa, M.; Benseny-Cases, N.; Cócera, M.; Teixeira, C. V.; Alsina, M.; Cladera, J.; López, O.; Fernández, M.; Sabés, M.

In previous chapters, the basis of SAXS for the study of biological systems like proteins in solution have been presented. The SAXS patterns of proteins in solution present, in general, broad dependences with the scattering vector, and the interpretation requires a huge component of modelling. In this chapter and in the following one, it is shown how SAXS technique can be used to study biological systems that are partially crystalline and with a large crystalline cells. This is done by analysing the diffraction obtained from these systems at small angles. In this chapter, a new approach to the application of small-angle X-ray scattering (SAXS) for diagnosis using the diffraction pattern of collagen is presented. This chapter shows the development of a new strategy in the preventive diagnosis of breast cancer following changes on collagen from breast connective tissue. SAXS profiles are related to different features in cutaneous preparations and to the supra-molecular arrangement of skin layers (stratum corneum, epidermis and dermis), in order to introduce objective values on the diagnosis of different skin pathologies. Working parameters (size, thickness) and methods (freezing, paraffin embedment) have been established. The results suggest that collagen diffraction patterns could be used as diagnostic indicators; especially for breast cancer and preliminary results obtained with skin collagen are promising too.

Review of applications of microneedling in dermatology

PubMed Central

Iriarte, Christopher; Awosika, Olabola; Rengifo-Pardo, Monica; Ehrlich, Alison

2017-01-01

Microneedling (MN) is a novel therapeutic modality in dermatology. Through physical trauma from needle penetration, MN induces a wound healing cascade with minimal damage to the epidermis. This allows for enhancement in the absorption of mainstay topical therapies across the thick stratum corneum. MN has become increasingly utilized over the last several years as it is a relatively simple procedure that is cost-effective, well tolerated, and offers both cosmetic and therapeutic benefits. The ability to treat localized areas of disease has led to numerous studies gauging its potential in focal diseases of inflammation, dyschromia, and photodamage. This review discusses the principles and evidence behind the expanding applications of MN. It has shown promising results as an adjuvant therapy for enhanced drug delivery in the treatment of atrophic scars, alopecia, actinic keratoses, and disorders of pigmentation such as melasma. The efficacy in treatment of vitiligo remains limited. Overall, the procedure has few adverse sequelae compared to other therapies, is highly efficacious, and is a viable resurfacing option for skin of color. Future research is needed to determine the frequency, interval, and specific device settings that foster optimal results. Additionally, large controlled trials are needed to shed light on the utility of MN as an evidence-based regimen for the treatment of various dermatologic conditions. PMID:28848356

Cosmetic formulations containing Lithospermum erythrorhizon root extract show moisturizing effects on human skin.

PubMed

Chang, Man-Jau; Huang, Huey-Chun; Chang, Hsien-Cheh; Chang, Tsong-Min

2008-07-01

Retention of water in the stratum corneum of skin epidermis plays an important role in regulation of skin function. Loss of water may decline skin appearance gradually and lead to irregular skin disorders. The root extract of Lithospermum erythrorhizon (LES) is known for its various pharmacological activities. However, the potential skin care effect of LES is not clear. The aim of this study was to evaluate the moisturizing efficacy and skin barrier repairing activity of LES. For this study, 30 healthy Asian females (age 20-30) with healthy skin had applied the test emulsions twice daily over a period of 28 days. The skin properties were measured by skin bioengineering techniques. Our preliminary results indicated that LES show moisturizing effect on skin hydration in a time- and dose-dependent pattern, and the maximum increase in skin humidity was 11.77 +/- 1.18% for emulsion LES5.00. Particularly, LES-containing emulsions significantly improve skin barrier function by decreasing the value of transepidermal water loss (TEWL) in a time- and dose-dependent pattern, and the maximum decrease in TEWL value was 7.68 +/- 0.79% for emulsion LES5.00. Taken together, our data demonstrate that LES is more effective in increasing skin humidity and decreasing the TEWL values, indicating the potential skin care effects of LES.

Estimation of skin concentrations of topically applied lidocaine at each depth profile.

PubMed

Oshizaka, Takeshi; Kikuchi, Keisuke; Kadhum, Wesam R; Todo, Hiroaki; Hatanaka, Tomomi; Wierzba, Konstanty; Sugibayashi, Kenji

2014-11-20

Skin concentrations of topically administered compounds need to be considered in order to evaluate their efficacies and toxicities. This study investigated the relationship between the skin permeation and concentrations of compounds, and also predicted the skin concentrations of these compounds using their permeation parameters. Full-thickness skin or stripped skin from pig ears was set on a vertical-type diffusion cell, and lidocaine (LID) solution was applied to the stratum corneum (SC) in order to determine in vitro skin permeability. Permeation parameters were obtained based on Fick's second law of diffusion. LID concentrations at each depth of the SC were measured using tape-stripping. Concentration-depth profiles were obtained from viable epidermis and dermis (VED) by analyzing horizontal sections. The corresponding skin concentration at each depth was calculated based on Fick's law using permeation parameters and then compared with the observed value. The steady state LID concentrations decreased linearly as the site became deeper in SC or VED. The calculated concentration-depth profiles of the SC and VED were almost identical to the observed profiles. The compound concentration at each depth could be easily predicted in the skin using diffusion equations and skin permeation data. Thus, this method was considered to be useful for promoting the efficient preparation of topically applied drugs and cosmetics. Copyright © 2014 Elsevier B.V. All rights reserved.

Enantioselective penetration enhancing effect of carvone on the in vitro transdermal permeation of nicorandil.

PubMed

Krishnaiah, Yellela S R; Nada, Aly

2012-01-01

The objective was to investigate the difference in penetration enhancing effect of R-carvone, S-carvone and RS-carvone on the in vitro transdermal drug permeation. In vitro permeation studies were carried out across neonatal rat epidermis from 2%w/v HPMC (hydroxypropyl methylcellulose) gel containing 4%w/v of nicorandil (a model drug) and a selected concentration (12%w/v) of either R-carvone, S-carvone or RS-carvone against a control. The stratum corneum (SC) of rats was treated with vehicle (70%v/v ethanol-water) or ethanolic solutions of 12%w/v R-carvone, S-carvone or RS-carvone. The enhancement ratio (ER) of R-carvone, S-carvone and RS-carvone when compared to control was about 37.1, 31.2 and 29.9, respectively indicating enantioselective penetration enhancing effect of carvone enantiomers. Furthermore, there was a significant decrease in the lag time required to produce a steady-state flux of nicorandil with S-carvone when compared to R-carvone and RS-carvone. DSC and FT-IR studies indicate that the investigated enantiomers of carvone exhibit a difference in their ability to affect the cellular organization of SC lipids and proteins thereby showing enantioselective transdermal drug permeation. It was concluded that R-carvone exhibited a higher penetration enhancing activity on transdermal permeation of nicorandil when compared to its S-isomer or racemic mixture.

Time-resolved singlet oxygen luminescence detection under photodynamic therapy relevant conditions: comparison of ex vivo application of two photosensitizer formulations

NASA Astrophysics Data System (ADS)

Schlothauer, Jan C.; Hackbarth, Steffen; Jäger, Lutz; Drobniewski, Kai; Patel, Hemantbhai; Gorun, Sergiu M.; Röder, Beate

2012-11-01

Singlet oxygen plays a crucial role in photo-dermatology and photodynamic therapy (PDT) of cancer. Its direct observation by measuring the phosphorescence at 1270 nm, however, is still challenging due to the very low emission probability. It is especially challenging for the time-resolved detection of singlet oxygen kinetics in vivo which is of special interest for biomedical applications. Photosensitized generation of singlet oxygen, in pig ear skin as model for human skin, is investigated here. Two photosensitizers (PS) were topically applied to the pig ear skin and examined in a comparative study, which include the amphiphilic pheophorbide-a and the highly hydrophobic perfluoroalkylated zinc phthalocyanine (F64PcZn). Fluorescence microscopy indicates the exclusive accumulation of pheophorbide-a in the stratum corneum, while F64PcZn can also accumulate in deeper layers of the epidermis of the pig ear skin. The kinetics obtained with phosphorescence measurements show the singlet oxygen interaction with the PS microenvironment. Different generation sites of singlet oxygen correlate with the luminescence kinetics. The results show that singlet oxygen luminescence detection can be used as a diagnostic tool, not only for research, but also during treatment. The detection methodology is suitable for the monitoring of chemical quenchers' oxidation as well as O2 saturation at singlet oxygen concentration levels relevant to PDT treatment protocols.

In vitro efficacy and release study with anti-inflammatory drugs incorporated in adhesive transdermal drug delivery systems.

PubMed

Meyer, Stefanie; Peters, Nils; Mann, Tobias; Wolber, Rainer; Pörtner, Ralf; Nierle, Jens

2014-04-01

The topical application of two different anti-inflammatory extracts incorporated in adhesive transdermal drug delivery systems (TDDSs) was investigated. Therefore, anti-inflammatory properties and percutaneous absorption behavior of adhesive TDDSs were characterized in vitro conducting experiments with a dermatologically relevant human skin model. Anti-inflammatory efficacy against UV irradiation of both TDDSs was determined in vitro with EpiDerm™. The reduction of the release of proinflammatory cytokines by topically applied TDDSs was compared with the reduction during the presence of the specific cyclooxygenase inhibitor diclofenac in the culture medium. A similar anti-inflammatory efficacy of the topically applied TDDSs in comparison with the use of diclofenac in the culture medium should be achieved. Furthermore, percutaneous absorption in efficacy tests was compared with percutaneous absorption in diffusion studies with porcine cadaver skin. Both the topically applied TDDSs showed a significant anti-inflammatory activity. Permeation coefficients through the stratum corneum and the epidermis gained from the release studies on porcine cadaver skin (Magnolia: 2.23·10(-5) cm/h, licorice: 4.68·10(-6) cm/h) were approximately five times lower than the permeation coefficients obtained with the EpiDerm™ skin model (Magnolia: 9.48·10(-5) cm/h, licorice: 24.0·10(-6) cm/h). Therefore, an adjustment of drug doses during experiments with the EpiDerm™ skin model because of weaker skin barrier properties should be considered.

Development and characterization of multiple emulsions for controlled release of Trichilia catigua (Catuaba) extract.

PubMed

Lonni, Audrey Alesandra Stinghen Garcia; Munhoz, Vanessa Marquito; Lopes, Gisely Cristiny; Longhini, Renata; Borghi-Pangoni, Fernanda Belincanta; Dos Santos, Rafaela Said; Junqueira, Mariana Volpato; Natali, Maria Raquel Marçal; Leite-Mello, Eneri; Guimaraes, Francine Baesso; Baesso, Mauro Luciano; Scarminio, Ieda Spacino; Bruschi, Marcos Luciano; Mello, João Carlos Palazzo de

2016-12-01

Considering the antioxidant activity of the Trichilia catigua extract (TCE), the aim of the current study was to develop and characterize W/O/W multiple emulsions containing different vegetable oils as a platform to deliver a TCE. The extract displayed antioxidant activity (IC 50 ) of 4.59 µg/mL and total phenol content (TPC) of 50.84%. Formulations were prepared by the phase-inversion emulsification method and analyzed for morphological appearance, pH, conductivity, droplet size and distribution, content of active, rheological properties, in vitro release, skin permeation, and stability. Formulations prepared with canola oil were selected and displayed regular morphology, mean diameter 2.77 µm (without TCE), 3.07 µm with 0.5% and 3.23 µm with 1.0% TCE. Rheometry (flow) showed pseudoplastic behavior with minimal thixotropy for both systems. TCE could be released from emulsions containing 1.0% and 0.5% TCE in a controlled manner for 16 and 23 h, respectively. The emulsions allowed good retention of TCE in the skin (stratum corneum, epidermis, and dermis). In a 180-d assessment of accelerated chemical stability, TPC was more reduced for the emulsions at 40 °C; other parameters remained stable. Multiple emulsions containing TCE were developed, exhibited good characteristics, and may be considered for future investigations as anti-aging formulations for the skin.

Penetration and decontamination of americium-241 ex vivo using fresh and frozen pig skin.

PubMed

Tazrart, A; Bolzinger, M A; Moureau, A; Molina, T; Coudert, S; Angulo, J F; Briancon, S; Griffiths, N M

2017-04-01

Skin contamination is one of the most probable risks following major nuclear or radiological incidents. However, accidents involving skin contamination with radionuclides may occur in the nuclear industry, in research laboratories and in nuclear medicine departments. This work aims to measure the penetration of the radiological contaminant Americium ( 241 Am) in fresh and frozen skin and to evaluate the distribution of the contamination in the skin. Decontamination tests were performed using water, Fuller's earth and diethylene triamine pentaacetic acid (DTPA), which is the recommended treatment in case of skin contamination with actinides such as plutonium or americium. To assess these parameters, we used the Franz cell diffusion system with full-thickness skin obtained from pigs' ears, representative of human skin. Solutions of 241 Am were deposited on the skin samples. The radioactivity content in each compartment and skin layers was measured after 24 h by liquid scintillation counting and alpha spectrophotometry. The Am cutaneous penetration to the receiver compartment is almost negligible in fresh and frozen skin. Multiple washings with water and DTPA recovered about 90% of the initial activity. The rest remains fixed mainly in the stratum corneum. Traces of activity were detected within the epidermis and dermis which is fixed and not accessible to the decontamination. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A dermatotoxicokinetic model of human exposures to jet fuel.

PubMed

Kim, David; Andersen, Melvin E; Nylander-French, Leena A

2006-09-01

Workers, both in the military and the commercial airline industry, are exposed to jet fuel by inhalation and dermal contact. We present a dermatotoxicokinetic (DTK) model that quantifies the absorption, distribution, and elimination of aromatic and aliphatic components of jet fuel following dermal exposures in humans. Kinetic data were obtained from 10 healthy volunteers following a single dose of JP-8 to the forearm over a surface area of 20 cm2. Blood samples were taken before exposure (t = 0 h), after exposure (t = 0.5 h), and every 0.5 h for up to 3.5 h postexposure. The DTK model that best fit the data included five compartments: (1) surface, (2) stratum corneum (SC), (3) viable epidermis, (4) blood, and (5) storage. The DTK model was used to predict blood concentrations of the components of JP-8 based on dermal-exposure measurements made in occupational-exposure settings in order to better understand the toxicokinetic behavior of these compounds. Monte Carlo simulations of dermal exposure and cumulative internal dose demonstrated no overlap among the low-, medium-, and high-exposure groups. The DTK model provides a quantitative understanding of the relationship between the mass of JP-8 components in the SC and the concentrations of each component in the systemic circulation. The model may be used for the development of a toxicokinetic modeling strategy for multiroute exposure to jet fuel.

Effects of Hydroxydecine(®) (10-hydroxy-2-decenoic acid) on skin barrier structure and function in vitro and clinical efficacy in the treatment of UV-induced xerosis.

PubMed

Duplan, Hélène; Questel, Emmanuel; Hernandez-Pigeon, Hélène; Galliano, Marie Florence; Caruana, Antony; Ceruti, Isabelle; Ambonati, Marco; Mejean, Carine; Damour, Odile; Castex-Rizzi, Nathalie; Bessou-Touya, Sandrine; Schmitt, Anne-Marie

2011-01-01

10-Hydroxy-2-decenoic acid, a natural fatty acid only found in royal jelly, may be of value in correcting skin barrier dysfunction. We evaluated the activity of Hydroxydecine(®), its synthetic counterpart, in vitro on the regulation of epidermal differentiation markers, ex vivo on the inflammatory response and restoration of skin barrier function, and in vivo on UV-induced xerosis in healthy human volunteers. In cultured normal human keratinocytes, Hydroxydecine(®) induced involucrin, transglutaminase-1 and filaggrin protein production. In topically Hydroxydecine(®)-treated skin equivalents, immunohistochemical analysis revealed an increase in involucrin, transglutaminase-1 and filaggrin staining. In a model of thymic stromal lymphopoietin (TSLP)-induced inflamed epidermis, a Hydroxydecine(®)-containing emulsion inhibited TSLP release. In a model of inflammation and barrier impairment involving human skin explants maintained alive, Hydroxydecine(®) balm restored stratum corneum cohesion and significantly increased filaggrin expression, as shown by immunohistochemistry. It also decreased pro-inflammatory cytokine secretion (IL-4, IL-5 and IL-13). In healthy volunteers with UV-induced xerosis, the hydration index increased by +28.8% (p<0.01) and +60.4% (p<0.001) after 7 and 21 days of treatment with Hydroxydecine(®) cream, respectively. Hydroxydecine(®) thus proved its efficacy in activating keratinocyte differentiation processes in vitro, restoring skin barrier function and reducing inflammation ex vivo, and hydrating dry skin in vivo.

Why minimally invasive skin sampling techniques? A bright scientific future.

PubMed

Wang, Christina Y; Maibach, Howard I

2011-03-01

There is increasing interest in minimally invasive skin sampling techniques to assay markers of molecular biology and biochemical processes. This overview examines methodology strengths and limitations, and exciting developments pending in the scientific community. Publications were searched via PubMed, the U.S. Patent and Trademark Office Website, the DermTech Website and the CuDerm Website. The keywords used were noninvasive skin sampling, skin stripping, skin taping, detergent method, ring method, mechanical scrub, reverse iontophoresis, glucose monitoring, buccal smear, hair root sampling, mRNA, DNA, RNA, and amino acid. There is strong interest in finding methods to access internal biochemical, molecular, and genetic processes through noninvasive and minimally invasive external means. Minimally invasive techniques include the widely used skin tape stripping, the abrasion method that includes scraping and detergent, and reverse iontophoresis. The first 2 methods harvest largely the stratum corneum. Hair root sampling (material deeper than the epidermis), buccal smear, shave biopsy, punch biopsy, and suction blistering are also methods used to obtain cellular material for analysis, but involve some degree of increased invasiveness and thus are only briefly mentioned. Existing and new sampling methods are being refined and validated, offering exciting, different noninvasive means of quickly and efficiently obtaining molecular material with which to monitor bodily functions and responses, assess drug levels, and follow disease processes without subjecting patients to unnecessary discomfort and risk.

Effect of lipophilicity on in vivo iontophoretic delivery. II. Beta-blockers.

PubMed

Tashiro, Y; Sami, M; Shichibe, S; Kato, Y; Hayakawa, E; Itoh, K

2001-06-01

The objective of this study was to investigate the relationship between drug lipophilicity and the transdermal absorption processes in the iontophoretic delivery in vivo. Anodal iontophoresis of beta-blockers as model drugs having different lipophilicity (atenolol, pindolol, metoprolol, acebutolol, oxprenolol and propranolol) was performed with rats (electrical current, 0.625 mA/cm2; application period, 90 min), and the drug concentrations in skin, cutaneous vein and systemic vein were determined. Increasing the lipophilicity of beta-blockers caused a greater absorption into the skin. Exceptionally, it was found that pindolol had high skin absorption, irrespective of its hydrophilic nature. Further, the drug transfer rate from skin to cutaneous vein (R(SC)) was evaluated from the arterio-venous plasma concentration difference of drug in the skin. Normalized R(SC) by skin concentration showed a negative correlation with the logarithm of n-octanol/buffer partition coefficient (Log P, pH 7.4), suggesting the partitioning between stratum corneum and viable epidermis was a primary process to determine the transfer properties of beta-blockers to local blood circulation. Pindolol exhibited both high skin absorption and high transfer from skin to cutaneous vein. These characteristics of pindolol could be explained by the chemical structure, molecular size and hydrophilicity. These findings for pindolol should be valuable for the optimal design of drug candidates for iontophoretic transdermal delivery.

Models of wound healing: an emphasis on clinical studies.

PubMed

Wilhelm, K-P; Wilhelm, D; Bielfeldt, S

2017-02-01

The healing of wounds has always provided challenges for the medical community whether chronic or acute. Understanding the processes which enable wounds to heal is primarily carried out by the use of models, in vitro, animal and human. It is generally accepted that the use of human models offers the best opportunity to understand the factors that influence wound healing as well as to evaluate efficacy of treatments applied to wounds. The objective of this article is to provide an overview of the different methodologies that are currently used to experimentally induce wounds of various depths in human volunteers and examines the information that may be gained from them. There is a number of human volunteer healing models available varying in their invasiveness to reflect the different possible depth levels of wounds. Currently available wound healing models include sequential tape stripping, suction blister, abrasion, laser, dermatome, and biopsy techniques. The various techniques can be utilized to induce wounds of variable depth, from removing solely the stratum corneum barrier, the epidermis to even split-thickness or full thickness wounds. Depending on the study objective, a number of models exist to study wound healing in humans. These models provide efficient and reliable results to evaluate treatment modalities. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

In vivo histological evaluation of non-insulated microneedle radiofrequency applicator with novel fractionated pulse mode.

PubMed

Harth, Yoram; Frank, Ido

2013-12-01

Microneedle radiofrequency is a novel method that allows non-thermal penetration of the epidermis followed by RF coagulation in selected depth of the dermis surrounded by zone of non-coagulative volumetric heating. The first generation of Microneedle RF applicators used insulated needles. These treatments were limited by a few factors, including low volume of dermal heating, lack of effect in the papillary dermis and pinpoint bleeding during the treatment. The system tested in this study (EndyMed PRO, Intensif applicator, EndyMed Medical, Cesarea, Israel) utilizes special extra sharp tapered non-insulated microneedles and a special pulse mode, allowing full coagulation during treatment and higher effective volume of dermal heat. After Ethics Committee approval, one female pig (Type Large white X Landrace, 34 Kg) was chosen for the study. The animal was anesthetized using Ketamine, Xylazin and Isofluran. The EndyMed PRO, Intensif applicator (was used for treatment with different needle depth penetration (1 mm-3.5 mm) and in multiple energy settings. Six mm punch biopsies were harvested for histological analysis at the following time points: immediately after the treatment, 4 days after the treatment and 14 days after the treatment. H&E and Masson-Trichrome stains were processed. Visual inspection of the treated skin, immediately after the treatment, revealed arrays of pinpoint erythematous papules surrounded by undamaged epidermal tissue. Treatment field showed no sign of bleeding. Mild to moderate Erythema and Edema developed a few minutes after the treatment, varying according to the total energy delivered. The histologies taken 4-day after therapy showed in all energy settings, dry micro crusts over the treatment zones, with full healing of epidermis. In the 14-day specimens there was a replacement of the crusts/debris by a normal looking stratum corneum with complete healing of epidermis and dermis. The current in vivo study confirms that the EndyMed PRO

VASCULARIZED COMPOSITE ALLOGRAFT TRANSPLANT SURVIVAL IN MINIATURE SWINE: IS MHC TOLERANCE SUFFICIENT FOR ACCEPTANCE OF EPIDERMIS?

PubMed Central

Cetrulo, Curtis L.; Torabi, Radbeh; Scalea, Joseph R.; Shimizu, Akira; Leto Barone, Angelo A.; Gillon, Brad C.; Tasaki, Masayuki; Leonard, David A.; Cormack, Taylor A.; Villani, Vincenzo; Randolph, Mark A.; Sachs, David H.; Yamada, Kazuhiko

2014-01-01

Background We have previously reported that MGH miniature swine which had accepted class-I mismatched kidneys long-term (LT) following 12 days of high dose Cyclosporine (CyA), uniformly accepted donor-MHC matched kidneys without immunosuppression but rejected donor-MHC matched split-thickness skin grafts (STSG) by day 25, without changes in renal graft function or anti-donor in vitro responses. We have now tested whether this “split tolerance” would also be observed for the primarily-vascularized skin of vascularized composite allografts (VCAs). Methods Group 1 animals (n=3) received donor-MHC matched VCAs <70 days following primary kidney transplant (KTx). Group 2 animals (n=3) received a second donor-matched t KTx followed by a donor-matched VCA >200 days after primary KTx. Results Animals in Group 1 lost the epidermis on days 28, 30, and 40, with all other components of the VCAs remaining viable. Histology showed cellular infiltration localized to dermal-epidermal junction. One of 3 recipients of VCAs including epidermis in Group 2 accepted all components of the VCAs (>200 days). The other two recipients lost only the epidermis at day 45 and 85, with survival of the remainder of the VCA long-term. Conclusions All tissues of a VCA are accepted long-term on animals tolerant of class-I mismatched kidneys, with the exception of epidermis, the survival of which is markedly prolonged compared to STSG, but not indefinite. Exposure of tolerant animals to second donor-matched kidneys prior to VCA increases the longevity of the VCA epidermis, suggesting an increase in the immunomodulatory mechanisms associated with tolerance of the kidney. PMID:24056624

Synthesis of Very-Long-Chain Fatty Acids in the Epidermis Controls Plant Organ Growth by Restricting Cell Proliferation

PubMed Central

Nobusawa, Takashi; Okushima, Yoko; Nagata, Noriko; Kojima, Mikiko; Sakakibara, Hitoshi; Umeda, Masaaki

2013-01-01

Plant organ growth is controlled by inter-cell-layer communication, which thus determines the overall size of the organism. The epidermal layer interfaces with the environment and participates in both driving and restricting growth via inter-cell-layer communication. However, it remains unknown whether the epidermis can send signals to internal tissue to limit cell proliferation in determinate growth. Very-long-chain fatty acids (VLCFAs) are synthesized in the epidermis and used in the formation of cuticular wax. Here we found that VLCFA synthesis in the epidermis is essential for proper development of Arabidopsis thaliana. Wild-type plants treated with a VLCFA synthesis inhibitor and pasticcino mutants with defects in VLCFA synthesis exhibited overproliferation of cells in the vasculature or in the rib zone of shoot apices. The decrease of VLCFA content increased the expression of IPT3, a key determinant of cytokinin biosynthesis in the vasculature, and, indeed, elevated cytokinin levels. These phenotypes were suppressed in ipt3;5;7 triple mutants, and also by vasculature-specific expression of cytokinin oxidase, which degrades active forms of cytokinin. Our results imply that VLCFA synthesis in the epidermis is required to suppress cytokinin biosynthesis in the vasculature, thus fine-tuning cell division activity in internal tissue, and therefore that shoot growth is controlled by the interaction between the surface (epidermis) and the axis (vasculature) of the plant body. PMID:23585732

Hand hygiene and skin health.

PubMed

Kownatzki, E

2003-12-01

The high rate of hand problems associated with the hand hygiene of medical professions is due to a combination of damaging factors: (1) the removal of barrier lipids by detergent cleaning and alcohol antisepsis followed by a loss of moisturizers and stratum corneum water and (2) the overhydration of the stratum corneum by sweat trapped within gloves. Together the facilitate the invasion of irritants and allergens which elicit inflammatory responses in the dermis. Among the lipids and water-soluble substances removed are natural antibacterials. Their loss leads to increased growth of transient and pathogenic micro-organisms which jeapordizes the very intention of skin hygiene. The kinetics of damage and its repair, and epidemiological evidence suggest that modern synthetic detergents as used in foaming liquid cleansers are the major offender. Conversely, the replacement of detergents with non-detergent emulsion cleansers has been shown to be effective in reducing the prevalence of hand problems among hospital staff. Presently recommended hand antisepsis reduces the risks to patients, but puts the burden on the health care provider. Rather than fighting micro-organisms at the expense of the skin's health, the skin and its own defences should be considered a collaborator in combating infectious diseases.

Usefulness and pharmacokinetic study of oral terbinafine for hyperkeratotic type tinea pedis.

PubMed

Kikuchi, Izumi; Tanuma, Hiroyuki; Morimoto, Kensuke; Kawana, Seiji

2008-01-01

To study and establish an optimal administration method of oral antifungal, terbinafine (TBF), for hyperkeratotic type tinea pedis, from the pharmacokinetic point of view, 20 patients with hyperkeratotic type tinea pedis were given TBF 125 mg once daily for 4 weeks and observed over time for improvement in dermatological symptoms and mycological efficacy. Targeting five of the patients, TBF concentration in the stratum corneum was measured using the liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. TBF was detected in the stratum corneum of the sole 1 week after beginning the treatment in some cases and reached its peak 1 week after the completion of the treatment with a concentration of 247.8 ng g(-1), which was approximately more than 50 times higher than its minimal inhibitory concentration against dermatophytes. TBF was not detected at 8 weeks post-treatment, although its concentration was 50.73 ng g(-1) at 6 weeks post-treatment. Its effectiveness rate (effective + markedly effective) was 95% (19/20) with no adverse reactions, including abnormal changes in the laboratory test values, in any patient. These results suggest that TBF is a useful drug to treat hyperkeratotic tinea pedis from the pharmacokinetic point of view.

Evaluation of psychological stress in confined environments using salivary, skin, and facial image parameters.

PubMed

Egawa, Mariko; Haze, Shinichiro; Gozu, Yoko; Hosoi, Junichi; Onodera, Tomoko; Tojo, Yosuke; Katsuyama, Masako; Hara, Yusuke; Katagiri, Chika; Inoue, Natsuhiko; Furukawa, Satoshi; Suzuki, Go

2018-05-29

Detecting the influence of psychological stress is particularly important in prolonged space missions. In this study, we determined potential markers of psychological stress in a confined environment. We examined 23 Japanese subjects staying for 2 weeks in a confined facility at Tsukuba Space Center, measuring salivary, skin, and facial image parameters. Saliva was collected at four points in a single day to detect diurnal variation. Increases in salivary cortisol were detected after waking up on the 4th and 11th days, and at 15:30 on the 1st and in the second half of the stay. Transepidermal water loss (TEWL) and sebum content of the skin were higher compared with outside the facility on the 4th and 1st days respectively. Increased IL-1β in the stripped stratum corneum was observed on the 14th day, and 7 days after leaving. Differences in facial expression symmetry at the time of facial expression changes were observed on 11th and 14th days. Thus, we detected a transition of psychological stress using salivary cortisol profiles and skin physiological parameters. The results also suggested that IL-1β in the stripped stratum corneum and facial expression symmetry are possible novel markers for conveniently detecting psychological stress.

Swept-source optical coherence tomography of lower limb wound healing with histopathological correlation

NASA Astrophysics Data System (ADS)

Barui, Ananya; Banerjee, Provas; Patra, Rusha; Das, Raunak Kumar; Dhara, Santanu; Dutta, Pranab K.; Chatterjee, Jyotirmoy

2011-02-01

Direct noninvasive visualization of wound bed with depth information is important to understand the tissue repair. We correlate skin swept-source-optical coherence tomography (OCT) with histopathological and immunohistochemical evaluation on traumatic lower limb wounds under honey dressing to compare and assess the tissue repair features acquired noninvasively and invasively. Analysis of optical biopsy identifies an uppermost brighter band for stratum corneum with region specific thickness (p < 0.0001) and gray-level intensity (p < 0.0001) variation. Below the stratum corneum, variation in optical intensities is remarkable in different regions of the wound bed. Correlation between OCT and microscopic observations are explored especially in respect to progressive growth and maturation of the epithelial and subepithelial components. Characteristic transition of uniform hypolucid band in OCT image for depigmented zone to wavy highly lucid band in the pigmented zone could be directly correlated with the microscopic findings. The transformation of prematured epithelium of depigmented area, with low expression of E-cadherin, to matured epithelium with higher E-cadherin expression in pigmented zone, implicated plausible change in their optical properties as depicted in OCT. This correlated evaluation of multimodal images demonstrates applicability of swept-source-OCT in wound research and importance of integrated approach in validation of new technology.

Skin surface hydration decreases rapidly during long distance flights.

PubMed

Guéhenneux, Sabine; Gardinier, Sophie; Morizot, Frederique; Le Fur, Isabelle; Tschachler, Erwin

2012-05-01

Dehydration of the stratum corneum leads to sensations and symptoms of 'dry skin' such as skin tightness and itchiness. As these complaints are frequently experienced by airline travellers, the aim of this study was to investigate the changes in skin surface hydration during long distance flights. The study was performed on four healthy Caucasian, and on four Japanese women aged 29-39 years, travelling on long distance flights. They had stopped using skin care products at least 12 h before, and did not apply them during the flights. The air temperature and relative humidity inside the cabin, as well as skin capacitance of the face and forearm of participants, were registered at several time points before and during the flights. Relative humidity of the aircraft cabin dropped to levels below 10% within 2 h after take-off and stayed at this value throughout the flight. Skin capacitance decreased rapidly on both the face and forearms with most pronounced changes on the cheeks where it decreased by up to 37%. Our results demonstrate that during long distance flights, the aircraft cabin environment leads to a rapid decrease in stratum corneum hydration, an alteration, which probably accounts for the discomfort experienced by long distance aircraft travellers. © 2011 John Wiley & Sons A/S.

Why pens have rubbery grips

NASA Astrophysics Data System (ADS)

Dzidek, Brygida; Bochereau, Séréna; Johnson, Simon A.; Hayward, Vincent; Adams, Michael J.

2017-10-01

The process by which human fingers gives rise to stable contacts with smooth, hard objects is surprisingly slow. Using high-resolution imaging, we found that, when pressed against glass, the actual contact made by finger pad ridges evolved over time following a first-order kinetics relationship. This evolution was the result of a two-stage coalescence process of microscopic junctions made between the keratin of the stratum corneum of the skin and the glass surface. This process was driven by the secretion of moisture from the sweat glands, since increased hydration in stratum corneum causes it to become softer. Saturation was typically reached within 20 s of loading the contact, regardless of the initial moisture state of the finger and of the normal force applied. Hence, the gross contact area, frequently used as a benchmark quantity in grip and perceptual studies, is a poor reflection of the actual contact mechanics that take place between human fingers and smooth, impermeable surfaces. In contrast, the formation of a steady-state contact area is almost instantaneous if the counter surface is soft relative to keratin in a dry state. It is for this reason that elastomers are commonly used to coat grip surfaces.

Establishment of an evaluation method to detect drug distribution in hair follicles.

PubMed

Abe, Akinari; Saito, Miyuki; Kadhum, Wesam R; Todo, Hiroaki; Sugibayashi, Kenji

2018-05-05

Development of an appropriate method to evaluate drug disposition or targeting ability in hair follicles (HFs) is urgently needed in order to develop useful pharmaceutical products with pharmacological effects in HFs. In the present study, a cyanoacrylate biopsy (CB) method was used to measure drug disposition in HFs using a model hydrophilic drug, caffeine (CAF), and a lipophilic drug, 4-butylresorcinol (BR), in excised porcine skin. As a result, the height of HF replicas and the recovery ratio decreased with an increase in the application times of the CB method. HF replicas with a length of approximately 175 µm were obtained using a single application of the CB method. Drug distribution in the HF was detected even 5 min after topical application regardless of the lipophilicity of the drugs, although no drug disposition was observed in the deeper layers of the stratum corneum at the same time (5 min). Furthermore, significantly higher amounts of BR were observed in the stratum corneum and HF, compared with those of CAF. These results suggested that the CB method could be useful to evaluate the safety and efficacy as well as the disposition of topically applied chemicals, especially for HF-targeting drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

A Mechanics Model for Sensors Imperfectly Bonded to the Skin for Determination of the Young's Moduli of Epidermis and Dermis.

PubMed

Yuan, J H; Shi, Y; Pharr, M; Feng, X; Rogers, John A; Huang, Yonggang

2016-08-01

A mechanics model is developed for the encapsulated piezoelectric thin-film actuators/sensors system imperfectly bonded to the human skin to simultaneously determine the Young's moduli of the epidermis and dermis as well as the thickness of epidermis.

Immunohistochemical distribution of Ki67 in epidermis of thick glabrous skin of human digits.

PubMed

Petrovic, Aleksandar; Petrovic, Vladimir; Milojkovic, Bobana; Nikolic, Ivan; Jovanovic, Dragan; Antovic, Aleksandra; Milic, Miroslav

2018-01-01

The glabrous skin on the flexor sides of hands and feet, compared to other integument regions, has thicker epidermis and more complex pattern of epidermal ridges, wherefore in microscopy is denominated as thick skin. The epidermis of this skin type has individually unique and permanent superficial patterns, called dermatoglyphics, which are maintained by regenerative potential of deep epidermal rete ridges, that interdigitate with adjacent dermis. Using light microscopy, we analyzed cadaveric big toes thick skin samples, described histology of deep epidermal ridges (intermediate, limiting, and transverse), and quantitatively evidenced their pattern of proliferation by immunohistochemical assessment of Ki67. Immunohistochemical distribution of Ki67 was confined to basal and suprabasal layers, with pattern of distribution specific for intermediate, limiting and transverse ridges that gradually transform within epidermal height. Deep epidermal ridges, interdigitating with dermal papillae, participate in construction of intricate epidermal base, whose possible role in epidermal regeneration was also discussed. Having a prominent morphology, this type of epidermis offers the best morphological insight in complexities of skin organization, and its understanding could challenge and improve currently accepted models of epidermal organization.

A Mechanics Model for Sensors Imperfectly Bonded to the Skin for Determination of the Young's Moduli of Epidermis and Dermis

PubMed Central

Yuan, J. H.; Shi, Y.; Pharr, M.; Feng, X.; Rogers, John A.; Huang, Yonggang

2016-01-01

A mechanics model is developed for the encapsulated piezoelectric thin-film actuators/sensors system imperfectly bonded to the human skin to simultaneously determine the Young's moduli of the epidermis and dermis as well as the thickness of epidermis. PMID:27330219

Antitumor-promoting activity of oligomeric proanthocyanidins in mouse epidermis in vivo

Treesearch

Xiao Mei Gao; Elisabeth M. Perchellet; Hala U. Gali; Limarie Rodriguez; Richard W. Hemingway; Jean-Pierre Perchellet

1994-01-01

The flavanoid catechin and heterogenous samples of oligomeric proanthocyanidins extracted from various sources were compared for their ability to inhibit the biochemical and biological effects of l2-0-tetradecanoylphorbol-13-acetate (TPA) in mouse epidermis in vivo. Topical applications of catechin fail to alter the hydroperoxide response to TPA but...

Investigating the "g"-Saturation of Various Stratum-Two Factors Using Automatic Item Generation

ERIC Educational Resources Information Center

Arendasy, Martin E.; Hergovich, Andreas; Sommer, Markus

2008-01-01

Even though researchers agree on the hierarchical structure of intelligence there is considerable disagreement on the g-saturation of the lower stratum-two factors. In this article it is argued that the mixed evidence in the research literature can be at least partially attributed to the construct representation of the individual tests used to…

A rapid, highly efficient and economical method of Agrobacterium-mediated in planta transient transformation in living onion epidermis.

PubMed

Xu, Kedong; Huang, Xiaohui; Wu, Manman; Wang, Yan; Chang, Yunxia; Liu, Kun; Zhang, Ju; Zhang, Yi; Zhang, Fuli; Yi, Liming; Li, Tingting; Wang, Ruiyue; Tan, Guangxuan; Li, Chengwei

2014-01-01

Transient transformation is simpler, more efficient and economical in analyzing protein subcellular localization than stable transformation. Fluorescent fusion proteins were often used in transient transformation to follow the in vivo behavior of proteins. Onion epidermis, which has large, living and transparent cells in a monolayer, is suitable to visualize fluorescent fusion proteins. The often used transient transformation methods included particle bombardment, protoplast transfection and Agrobacterium-mediated transformation. Particle bombardment in onion epidermis was successfully established, however, it was expensive, biolistic equipment dependent and with low transformation efficiency. We developed a highly efficient in planta transient transformation method in onion epidermis by using a special agroinfiltration method, which could be fulfilled within 5 days from the pretreatment of onion bulb to the best time-point for analyzing gene expression. The transformation conditions were optimized to achieve 43.87% transformation efficiency in living onion epidermis. The developed method has advantages in cost, time-consuming, equipment dependency and transformation efficiency in contrast with those methods of particle bombardment in onion epidermal cells, protoplast transfection and Agrobacterium-mediated transient transformation in leaf epidermal cells of other plants. It will facilitate the analysis of protein subcellular localization on a large scale.

A Rapid, Highly Efficient and Economical Method of Agrobacterium-Mediated In planta Transient Transformation in Living Onion Epidermis

PubMed Central

Xu, Kedong; Huang, Xiaohui; Wu, Manman; Wang, Yan; Chang, Yunxia; Liu, Kun; Zhang, Ju; Zhang, Yi; Zhang, Fuli; Yi, Liming; Li, Tingting; Wang, Ruiyue; Tan, Guangxuan; Li, Chengwei

2014-01-01

Transient transformation is simpler, more efficient and economical in analyzing protein subcellular localization than stable transformation. Fluorescent fusion proteins were often used in transient transformation to follow the in vivo behavior of proteins. Onion epidermis, which has large, living and transparent cells in a monolayer, is suitable to visualize fluorescent fusion proteins. The often used transient transformation methods included particle bombardment, protoplast transfection and Agrobacterium-mediated transformation. Particle bombardment in onion epidermis was successfully established, however, it was expensive, biolistic equipment dependent and with low transformation efficiency. We developed a highly efficient in planta transient transformation method in onion epidermis by using a special agroinfiltration method, which could be fulfilled within 5 days from the pretreatment of onion bulb to the best time-point for analyzing gene expression. The transformation conditions were optimized to achieve 43.87% transformation efficiency in living onion epidermis. The developed method has advantages in cost, time-consuming, equipment dependency and transformation efficiency in contrast with those methods of particle bombardment in onion epidermal cells, protoplast transfection and Agrobacterium-mediated transient transformation in leaf epidermal cells of other plants. It will facilitate the analysis of protein subcellular localization on a large scale. PMID:24416168

Investigations of percutaneous uptake of ultrafine TiO 2 particles at the high energy ion nanoprobe LIPSION

NASA Astrophysics Data System (ADS)

Menzel, F.; Reinert, T.; Vogt, J.; Butz, T.

2004-06-01

Micronised TiO 2 particles with a diameter of about 15 nm are used in sunscreens as physical UV filter. Due to the small particle size it may be supposed that TiO 2 particles can pass through the uppermost horny skin layer ( stratum corneum) via intercellular channels and penetrate into deeper vital skin layers. Accumulations of TiO 2 particles in the skin can decrease the threshold for allergies of the immune system or cause allergic reactions directly. Spatially resolved ion beam analysis (PIXE, RBS, STIM and secondary electron imaging) was carried out on freeze-dried cross-sections of biopsies of pig skin, on which four different formulations containing TiO 2 particles were applied. The investigations were carried out at the high energy ion nanoprobe LIPSION in Leipzig with a 2.25 MeV proton beam, which was focused to a diameter of 1 μm. The analysis concentrated on the penetration depth and on pathways of the TiO 2 particles into the skin. In these measurements a penetration of TiO 2 particles through the s. corneum into the underlying stratum granulosum via intercellular space was found. Hair follicles do not seem to be important penetration pathways because no TiO 2 was detected inside. The TiO 2 particle concentration in the stratum spinosum was below the minimum detection limit of about 1 particle/μm 2. These findings show the importance of coating the TiO 2 particles in order to prevent damage of RNA and DNA of skin cells by photocatalytic reactions of the penetrated particles caused by absorption of UV light.

Bovine rumen epithelium undergoes rapid structural adaptations during grain-induced subacute ruminal acidosis.

PubMed

Steele, Michael A; Croom, Jim; Kahler, Melissa; AlZahal, Ousama; Hook, Sarah E; Plaizier, Kees; McBride, Brian W

2011-06-01

Alterations in rumen epithelial structure and function during grain-induced subacute ruminal acidosis (SARA) are largely undescribed. In this study, four mature nonlactating dairy cattle were transitioned from a high-forage diet (HF; 0% grain) to a high-grain diet (HG; 65% grain). After feeding the HG diet for 3 wk, the cattle were transitioned back to the original HF diet, which was fed for an additional 3 wk. Continuous ruminal pH was measured on a weekly basis, and rumen papillae were biopsied during the baseline and at the first and final week of each diet. The mean, minimum, and maximum daily ruminal pH were depressed (P < 0.01) in the HG period compared with the HF period. During the HG period, SARA was diagnosed only during week 1, indicating ruminal adaptation to the HG diet. Microscopic examination of the papillae revealed a reduction (P < 0.01) in the stratum basale, spinosum, and granulosum layers, as well as total depth of the epithelium during the HG period. The highest (P < 0.05) papillae lesion scores were noted during week 1 when SARA occurred. Biopsied papillae exhibited a decline in cellular junctions, extensive sloughing of the stratum corneum, and the appearance of undifferentiated cells near the stratum corneum. Differential mRNA expression of candidate genes, including desmoglein 1 and IGF binding proteins 3, 5, and 6, was detected between diets using qRT-PCR. These results suggest that the structural integrity of the rumen epithelium is compromised during grain feeding and is associated with the differential expression of genes involved in epithelial growth and structure.

Antitumor-promoting activity of oligomeric proanthocyanidins in mouse epidermis in vivo

Treesearch

Mei Xiao Gao; Elisabeth M. Perchellet; Hala U. Gali; Limarie Rodriguez; Richard W. Hemingway; Jean-Pierre Perchellet

1994-01-01

The flavanoid catechin and heterogenous samples of oligomeric proanthocyanidins extracted from various sources were compared for their ability to inhibit the biochemical and biological effects of 12-o-tertra-decanoylphorbol-13-acetate (TPA) in mouse epidermis in vivo. Topical applications of catechin fail to alter the hydroperoxide response to TPA but inhibit the...

Effects of chalcone derivatives on lipoxygenase and cyclooxygenase activities of mouse epidermis.

PubMed

Nakadate, T; Aizu, E; Yamamoto, S; Kato, R

1985-09-01

The effects of chalcone derivatives on 12-lipoxygenase and cyclooxygenase of mouse epidermis were investigated. The chalcone derivatives which have 3,4-dihydroxycinnamoyl structure in the molecule, such as 3,4-dihydroxychalcone, 3,4,2'-trihydroxychalcone, 3,4,4'-trihydroxychalcone and 3,4,2'4'-tetrahydroxychalcone, potently inhibited epidermal 12-lipoxygenase activity. Although some of them also inhibited cyclooxygenase activity at relatively high concentrations, the inhibitory effects of these chalcone derivatives on 12-lipoxygenase were 10 times or more potent than their effects on cyclooxygenase. The chalcone derivatives which have cinnamoyl or 4-hydroxycinnamoyl structure, instead of 3,4-dihydroxycinnamoyl structure, in the molecule, showed little or no inhibitory effects on either 12-lipoxygenase or cyclooxygenase activities. The inhibitory effects of chalcone derivatives on 12-lipoxygenase and cyclooxygenase of mouse epidermis are dependent on the particular structure, i.e. 3,4-dihydroxycinnamoyl structure, of the chalcone derivatives.

Ambient humidity and the skin: the impact of air humidity in healthy and diseased states.

PubMed

Goad, N; Gawkrodger, D J

2016-08-01

Humidity, along with other climatic factors such as temperature and ultraviolet radiation, can have an important impact on the skin. Limited data suggest that external humidity influences the water content of the stratum corneum. An online literature search was conducted through Pub-Med using combinations of the following keywords: skin, skin disease, humidity, dermatoses, dermatitis, eczema, and mist. Publications included in this review were limited to (i) studies in humans or animals, (ii) publications showing relevance to the field of dermatology, (iii) studies published in English and (iv) publications discussing humidity as an independent influence on skin function. Studies examining environmental factors as composite influences on skin health are only included where the impact of humidity on the skin is also explored in isolation of other environmental factors. A formal systematic review was not feasible for this topic due to the heterogeneity of the available research. Epidemiological studies indicated an increase in eczema with low internal (indoors) humidity and an increase in eczema with external high humidity. Other studies suggest that symptoms of dry skin appear with low humidity internal air-conditioned environments. Murine studies determined that low humidity caused a number of changes in the skin, including the impairment of the desquamation process. Studies in humans demonstrated a reduction in transepidermal water loss (TEWL) (a measure of the integrity of the skin's barrier function) with low humidity, alterations in the water content in the stratum corneum, decreased skin elasticity and increased roughness. Intervention with a humidifying mist increased the water content of the stratum corneum. Conversely, there is some evidence that low humidity conditions can actually improve the barrier function of the skin. Ambient relative humidity has an impact on a range of parameters involved in skin health but the literature is inconclusive. Further

Dermal Influence on Epidermal Resurfacing during the Repair of Split Thickness Wounds.

DTIC Science & Technology

1983-08-15

by exposing purified platelets to thrombin also stimulated the proliferation of mooth muscle cells. They concluded that much of the growth-proanting...easily separated with forceps. The moist epidermis was placed on a microscope slide with the stratm corneum (and protruding hair shafts) against the glass...hcmogenate intradermally around the wound bed or using a viscous vehicle for the platelet factor, such as an ointment -based emollient. 3) The active factor

Ultrastructure and wear patterns of the ventral epidermis of four snake species (Squamata, Serpentes).

PubMed

Klein, Marie-Christin G; Gorb, Stanislav N

2014-10-01

Snakes are limbless tetrapods highly specialized for sliding locomotion. This locomotion leads to the skin being exposed to friction loads, especially on the ventral body side, which leads to wear. It is presumed that snakes therefore have specific optimizations for minimizing abrasion. Scales from snakes with habitat, locomotor and/or behavior specializations have specific gradients in material properties that may be due to different epidermal architecture. To approach this issue we examined the skin of Lampropeltis getula californiae (terrestrial), Epicrates cenchria cenchria (generalist), Morelia viridis (arboreal), and Gongylophis colubrinus (burrowing) with a focus on (i) the ultrastructure of the ventral epidermis and (ii) the qualitative abrasion pattern of the ventral scales. Scanning and transmission electron microscopy revealed variations in the structure, thickness, layering, and material composition of the epidermis between the species. Furthermore, SEM and white light interferometer images of the scale surface showed that the abrasion patterns differed, even when the snakes were reared on the same substrate. These data support the idea that (i) a specific gradient in material properties may be due to a variation in epidermis architecture (thickness/ultrastructure) and (ii) this variation may be an optimization of material properties for specific ways of life. Copyright © 2014 Elsevier GmbH. All rights reserved.

Evolution and genetics of root hair stripes in the root epidermis.

PubMed

Dolan, L; Costa, S

2001-03-01

Root hair pattern develops in a number of different ways in angiosperm. Cells in the epidermis of some species undergo asymmetric cell divisions to form a smaller daughter cell from which a hair grows, and a larger cell that forms a non-hair epidermal cell. In other species any cell in the epidermis can form a root hair. Hair cells are arranged in files along the Arabidopsis root, located in the gaps between underlying cortical cell files. Epidermal cells overlying a single cortical cell file develop as non-hair epidermal cells. Genetic analysis has identified a transcription factor cascade required for the formation of this pattern. WEREWOLF (WER) and GLABRA2 (GL2) are required for the formation of non-hair epidermal cells while CAPRICE (CPC) is required for hair cell development. Recent analyses of the pattern of epidermal cells among the angiosperms indicate that this striped pattern of cell organization evolved from non-striped ancestors independently in a number of diverse evolutionary lineages. The genetic basis for the evolution of epidermal pattern in angiosperms may now be examined.

Mathematical models to describe iontophoretic transport in vitro and in vivo and the effect of current application on the skin barrier.

PubMed

Gratieri, Taís; Kalia, Yogeshvar N

2013-02-01

The architecture and composition of the stratum corneum make it a particularly effective barrier against the topical and transdermal delivery of hydrophilic molecules and ions. As a result, different strategies have been explored in order to expand the range of therapeutic agents that can be administered by this route. Iontophoresis involves the application of a small electric potential to increase transport into and across the skin. Since current flow is preferentially via transport pathways with at least some aqueous character, it is ideal for hydrosoluble molecules containing ionisable groups. Hence, the physicochemical properties that limit partitioning and passive diffusion through the intercellular lipid matrix are beneficial for electrically-assisted delivery. The presence of fixed ionisable groups in the skin (pI 4-4.5) means that application of the electric field results in a convective solvent flow (i.e., electroosmosis) in the direction of ion motion so as to neutralise membrane charge. Hence, under physiological conditions, cation electrotransport is due to both electromigration and electroosmosis-their relative contribution depends on the formulation conditions and the physicochemical properties of the permeant. Different mathematical models have been developed to provide a theoretical framework in order to explain iontophoretic transport kinetics. They usually involve solutions of the Nernst-Planck equation - using either the constant field (Goldman) or electroneutrality (Nernst) approximations - with or without terms for the convective solvent flow component. Investigations have also attempted to elucidate the nature of ion transport pathways and to explain the effect of current application on the electrical properties of the skin-more specifically, the stratum corneum. These studies have led to the development of different equivalent circuit models. These range from simple parallel arrangements of a resistor and a capacitor to the inclusion of the

Time course of pH change in plant epidermis using microscopic pH imaging system

NASA Astrophysics Data System (ADS)

Dan, Risako; Shimizu, Megumi; Kazama, Haruko; Sakaue, Hirotaka

2010-11-01

We established a microscopic pH imaging system to track the time course of pH change in plant epidermis in vivo. In the previous research, we have found out that anthocyanin containing cells have higher pH. However, it was not clear whether the anthocyanin increased the pH or anthocyanin was synthesized result from the higher pH. Therefore, we further investigated the relationship between anthocyanin and pH change. To track the time course of pH change in plant epidermis, we established a system using luminescent imaging technique. We used HPTS (8-Hydroxypyrene-1,3,6-Trisulfonate) as pH indicator and applied excitation ratio imaging method. Luminescent image was converted to a pH distribution by obtained in vitro calibration using known pH solution. Cellular level observation was enabled by merging microscopic color picture of the same region to the pH change image. The established system was applied to epidermal cells of red-tip leaf lettuce, Lactuca Sativa L. and the time course was tracked in the growth process. We would discuss about the relationship between anthocyanin and pH change in plant epidermis.

Epidermal growth in the bottlenose dolphin, Tursiops truncatus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hicks, B.D.; St. Aubin, D.J.; Geraci, J.R.

1985-07-01

Epidermal growth in two mature female bottlenose dolphins, Tursiops truncatus, was investigated by following the movement of a cohort of tritiated thymidine-labeled epidermal cells for 59 days. The majority of the cells migrated in a cluster which was estimated to reach the skin surface in 73 days. The authors calculate that the outermost cell layer is sloughed 12 times per day. Turnover time and sloughing rate are estimated to be 1.7 times longer and 8.5 times faster than the respective values for epidermal cell kinetics in humans. This apparent inconsistency of slow transit time and rapid sloughing rate is reconciledmore » by the convoluted structure of the stratum germinativum in the dolphin which results in a ratio of germinatival to superficial cells of 876:1. The stratum germinativum of dolphin epidermis appears to lack morphologically distinct, spatially segregated subpopulations of anchoring and stem cells. Dolphin epidermis has a large capacity for cell population, relatively long turnover time, and rapid sloughing rate. The adaptive advantages of these characteristics are discussed.« less

The importance of consumption of the epidermis in malignant melanoma and correlation with clinicopathological prognostic parameters.

PubMed

Seçkin, Selda; Ozgũn, Elmas

2011-01-01

The aim of the study was to investigate the importance of consumption of the epidermis as an additional diagnostic criteria for malignant melanoma and to evaluate its relationship to clinicopathological findings. The age, gender, localization of the lesion and the histopathological parameters such as tumor type, Breslow thickness, ulceration, Clark's level, mitosis/mm2, lymphocytic infiltration were noted in 40 malignant melanoma cases. Consumption of the epidermis was evaluated in tumor sections. Consumption of the epidermis (COE) due to thinning of the epidermis and loss of rete ridges was noted as (+) or (-). Furthermore, COE was compared with clinical and histopathological parameters. The Shapiro Wilk and Logistic Regression tests were used for statistical analysis. The results were accepted as significant if the p value was < 0.05. COE was detected in 60% (24/40) of malignant melanoma cases. A positive correlation was present between COE and head and neck localization (p = 0,698), superficial spreading melanoma (p = 0,341), ulceration (p = 0,097) and brisk lymphocytic infiltration (p = 0,200) but the results were not statistically significant. COE was frequently detected in males but the difference was not statistically significant (p = 0.796). There was no correlation or significant statistical association between COE and age, Breslow thickness, Clark's level or the mitotic index. The detection of COE in most of the patients suggests that COE could be a histopathological criterion in the diagnosis of malignant melanoma. The frequent association between COE and the presence of ulceration could also direct attention to COE as regards prognostic importance.

Study of magnetic silk fibroin nanoparticles for massage-like transdermal drug delivery

PubMed Central

Chen, Ai-Zheng; Chen, Lin-Qing; Wang, Shi-Bin; Wang, Ya-Qiong; Zha, Jun-Zhe

2015-01-01

A synergistic approach by the combination of magnetic nanoparticles with an alternating magnetic field for transdermal drug delivery was investigated. Methotrexate-loaded silk fibroin magnetic nanoparticles were prepared using suspension-enhanced dispersion by supercritical CO2. The physiochemical properties of the magnetic nanoparticles were characterized. In vitro studies on drug permeation across skin were performed under different magnetic fields in comparison with passive diffusion. The permeation flux enhancement factor was found to increase under a stationary magnetic field, while an alternating magnetic field enhanced drug permeation more effectively; the combination of stationary and alternating magnetic fields, which has a massage-like effect on the skin, achieved the best result. The mechanistic studies using attenuated total reflection Fourier-transform infrared spectroscopy demonstrate that an alternating magnetic field can change the ordered structure of the stratum corneum lipid bilayers from the gel to the lipid-crystalline state, which can increase the fluidity of the stratum corneum lipids, thus enhancing skin penetration. Compared with the other groups, the fluorescence signal with a bigger area detected in deeper regions of the skin also reveals that the simulated massage could enhance the drug permeation across the skin by increasing the follicular transport. The combination of magnetic nanoparticles with stationary/alternating magnetic fields has potential for effective massage-like transdermal drug delivery. PMID:26229467

Skin penetration behaviour of sesquiterpene lactones from different Arnica preparations using a validated GC-MSD method.

PubMed

Wagner, Steffen; Merfort, Irmgard

2007-01-04

Preparations of Arnica montana L. are widely used for the topical treatment of inflammatory diseases. The anti-inflammatory activity is mainly attributed to their sesquiterpene lactones (SLs) from the helenalin and 11alpha,13-dihydrohelenalin type. To study the penetration kinetics of SLs in Arnica preparations, a stripping method with adhesive tape and pig skin as a model was used. For the determination of SLs in the stripped layers of the stratum corneum (SC), a gas chromatography/mass spectrometry method was developed and validated. Thereby the amount of helenalin derivatives was calculated as helenalin isobutyrate, and 11alpha,13-dihydrohelenalin derivatives as 11alpha,13-dihydrohelenalin methacrylate. This GC-MSD method is suitable also to determine low amounts of SLs in Arnica preparations. The penetration behaviour of one gel preparation and two ointment preparations was investigated. The SLs of all preparations show a comparable penetration in and a permeation through the stratum corneum, the uppermost part of the skin. Interestingly, the gel preparation showed a decrease of the penetration rate over 4h, whereas the penetration rate of ointments kept constant over time. Moreover, we could demonstrate that the totally penetrated amount of SLs only depends on the kind of the formulation and of the SLs-content in the formulation but not on the SLs composition or on the used extraction agent.

Localization of dexamethasone within dendritic core-multishell (CMS) nanoparticles and skin penetration properties studied by multi-frequency electron paramagnetic resonance (EPR) spectroscopy.

PubMed

Saeidpour, S; Lohan, S B; Anske, M; Unbehauen, M; Fleige, E; Haag, R; Meinke, M C; Bittl, R; Teutloff, C

2017-07-01

The skin and especially the stratum corneum (SC) act as a barrier and protect epidermal cells and thus the whole body against xenobiotica of the external environment. Topical skin treatment requires an efficient drug delivery system (DDS). Polymer-based nanocarriers represent novel transport vehicles for dermal application of drugs. In this study dendritic core-multishell (CMS) nanoparticles were investigated as promising candidates. CMS nanoparticles were loaded with a drug (analogue) and were applied to penetration studies of skin. We determined by dual-frequency electron paramagnetic resonance (EPR) how dexamethasone (Dx) labelled with 3-carboxy-2,2,5,5-tetramethyl-1-pyrrolidinyloxy (PCA) is associated with the CMS. The micro-environment of the drug loaded to CMS nanoparticles was investigated by pulsed high-field EPR at cryogenic temperature, making use of the fact that magnetic parameters (g-, A-matrices, and spin-lattice relaxation time) represent specific probes for the micro-environment. Additionally, the rotational correlation time of spin-labelled Dx was probed by continuous wave EPR at ambient temperature, which provides independent information on the drug environment. Furthermore, the penetration depth of Dx into the stratum corneum of porcine skin after different topical applications was investigated. The location of Dx in the CMS nanoparticles is revealed and the function of CMS as penetration enhancers for topical application is shown. Copyright © 2016 Elsevier B.V. All rights reserved.

Microemulsion and Microemulsion-Based Gels for Topical Antifungal Therapy with Phytochemicals.

PubMed

Boonme, Prapaporn; Kaewbanjong, Jarika; Amnuaikit, Thanaporn; Andreani, Tatiana; Silva, Amélia M; Souto, Eliana B

2016-01-01

Skin fungal infections are regular injuries suffered by people living in tropical areas. Most common pathogens are Trichophyton, Microsporum and Epidermophyton which can cause skin lesions in many parts of body. Topical antifungal phytochemicals are commonly used to avoid systemic adverse events and are more convenient for patient application than those administered by other routes. However, the effectiveness of topical treatments in eradicating fungal infection is more limited since the stratum corneum acts as the skin barrier, resulting in long treatment duration and low patient's compliance. The goal of this work is to identify optimized drug delivery systems to improve topic clinical efficacy. Microemulsions i.e. liquid dispersions of oil and water stabilized with an interfacial film of surfactant are well known drug delivery systems. A thickening agent may be included to form microemulsion-based gels to increase skin adhesion. Microemulsions and microemulsion-based gels can be loaded with several hydrophilic and lipophilic drugs because they are composed of both water and oil phases. Microemulsions and microemulsion-based gels can also be used for the delivery of many drugs including antifungal drugs through stratum corneum due to their capacity to act as skin penetration enhancement. In addition to a comprehensive review of microemulsion and microemulsion-based gels as suitable carriers for skin delivery of various antifungal drugs, this review also aims to discuss the delivery of antifungal phytochemicals.

Moisturizing and Antiinflammatory Properties of Cosmetic Formulations Containing Centella asiatica Extract