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Synopsis Objective The stratum corneum is the outermost layer of the skin. Its components and its morphology (such as the size of its cells) play a role in sun protection, and it has been noted that the stratum corneum hydration can change these properties. Sunscreens, applied on the skin, can be more or less effective depending on the stratum corneum characteristics. We therefore propose to simulate the quality of the sun protection and the effect of the stratum corneum hydration on the sun protection. Methods We first determined the sunscreen distribution on a plastic substrate using an optical coherence tomography device. We were then able to calculate, by 2-D differential method, the extinction of several sunscreens. We modelled the hydration of the stratum corneum, by changing the substrate with corneocytes of different thicknesses. Results Our results showed that hydrated stratum corneum protects more against the UV. The benefit from changing the substrate varies depending on the sunscreen applied. Conclusion We modelled sunscreens on different substrates using electromagnetic simulations. To compare these results with measurements, we have to carefully hydrate or dehydrate the SC: the simulations did not take into account modifications of the surface (water on the surface for example) or any change in the characteristics of the stratum corneum other than the modification of the corneocytes thickness. Resume Objectif La stratum corneum est la couche la plus externe de la peau. Ses composants et sa morphologie (comme la taille de ses cellules) jouent un role dans la protection solaire. Il a ainsi ete note que l'hydratation de cette couche change ses proprietes de protection. Les cremes solaires, appliquees sur la peau, peuvent etre plus ou moins efficaces selon les caracteristiques de la stratum corneum. Nous proposons ainsi de modeliser l'effet de l'hydratation de la stratum corneum sur la qualite des protections solaires. Methodes Dans un premier temps, nous determinons repartition de la creme sur un substrat en plastique par tomography a coherence optique. Nous pouvons alors calculer, en utilisant la methode differentielle en 2D, l'extinction de plusieurs cremes solaires. On modelise ensuite l'hydratation de la stratum corneum, en placant dans le substrat des corneocytes de differentes epaisseurs. Resultats Ces calculs nous ont permis de montrer que la couche de stratum corneum hydratee permet de mieux proteger contre les UV. Selon les cremes utilisees, le benefice gagnee est plus ou moins eleve. Conclusion Nous avons modelise par des calculs electromagnetiques des cremes solaires sur differents substrats. Afin de comparer ces resultats a des mesures, il faut faire attention a la facon d'hydrater ou de deshydrater la couche de stratum corneum: les simulations ne prennent pas en compte les modifications de la surface (par exemple l'eau qu'il pourrait y avoir), ou toute autre modification de la stratum corneum autre que la modification de l'epaisseur des corneocytes.

Stratum corneum (horny layer) is a superficial skin layer consisting of dead cells. To reveal in-depth penetration profiles of substances topically applied onto skin surface, a minimally invasive method called tape stripping is widely used. It introduces consecutive removal of micrometer-thick cell layers of stratum corneum from the same treated skin area using an adhesive tape. Prerequisite to the substance penetration profile is the reconstruction of the removed stratum corneum by analyzing the amount of corneocytes (cells of stratum corneum from) stuck to each tape strip. Before application in vivo on humans, porcine skin is often used for such kind of studies. In this paper, we present results of the experiments with porcine skin in vitro (ears of freshly slaughtered pigs) and compare them with those carried out on humans in vivo (flexor forearm) taken from references. As we proved experimentally, there is a linear dependence between the absorbance (equals to logarithm of inverse transmittance) and thickness of the corneocytes on tape strips for all wavelength of the investigated region (300-1050 nm). Dependence of the cumulative absorbance of removed stratum corneum on tape strip number can be satisfactory fitted by an exponential function. This relationship allows evaluation of the relative share of the removed stratum corneum without complete removal of the layer. All the obtained results correlate well with those obtained on humans.

The stratum corneum (SC), the outermost layer of the skin, provides the body with a physiologically essential barrier to unregulated water loss and the influx of exogenous substances. Furthermore, the 10–20 micron thick SC, composed of overlapping protein-rich corneocytes surrounded by a heterogeneous multilamellar lipid matrix, displays tremendous mechanical cohesion and thermal integrity. To understand the contribution of these components to SC mechanical properties requires building a complete mechanical model of the skin. In this study we focus on modelling the hierarchical microstructure of the lipid phase and its relation to mechanical properties using a combination of atomistic and mesoscale simulations. The modelling approaches are parameterised with experimental data from FT-IR spectroscopy, X-ray scattering and, in the case of the mesoscale simulations, with detailed density profiles derived from atomic models. The atomistic models are used to probe the role of specific lipid species in maintaining the thermal and structural stability of the SC extracellular lipid matrix and to investigate the role of hydrogen bonding networks in SC lipid cohesion. Mesoscale models are used to investigate domain formation and lipid bilayer organisation on length and time scales inaccessible with atomistic models. These coarse grained models display transitions between ordered hexagonal gel phases and fluid phases, reproducing the experimentally observed ordering of the hydrophilic and hydrophobic regions.

Adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) are limiting in cellular triglyceride catabolism. Although ATGL deficiency is compatible with normal skin development, mice globally lacking CGI-58 die postnatally and exhibit a severe epidermal permeability barrier defect, which may originate from epidermal and/or peripheral changes in lipid and energy metabolism. Here, we show that epidermis-specific disruption of CGI-58 is sufficient to provoke a defect in the formation of a functional corneocyte lipid envelope linked to impaired ω-O-acylceramide synthesis. As a result, epidermis-specific CGI-58-deficient mice show severe skin dysfunction, arguing for a tissue autonomous cause of disease development. Defective skin permeability barrier formation in global CGI-58-deficient mice could be reversed via transgenic restoration of CGI-58 expression in differentiated but not basal keratinocytes suggesting that CGI-58 is essential for lipid metabolism in suprabasal epidermal layers. The compatibility of ATGL deficiency with normal epidermal function indicated that CGI-58 may stimulate an epidermal triglyceride lipase beyond ATGL required for the adequate provision of fatty acids as a substrate for ω-O-acylceramide synthesis. Pharmacological inhibition of ATGL enzyme activity similarly reduced triglyceride-hydrolytic activities in wild-type and CGI-58 overexpressing epidermis implicating that CGI-58 participates in ω-O-acylceramide biogenesis independent of its role as a coactivator of epidermal triglyceride catabolism.

Background: Loss-of-function (LOF) mutations in the filaggrin gene (FLG) are a well-replicated risk factor for atopic dermatitis (AD) and are known to cause an epidermal barrier defect. The nature of this barrier defect is not fully understood. Patients with AD with FLG LOF mutations are known to have more persistent disease, more severe disease, and greater risk of food allergies and eczema herpeticum. Abnormalities in corneocyte morphology have been observed in patients with AD, including prominent villus-like projections (VP); however, these ultrastructural features have not been systematically studied in patients with AD in relation to FLG genotype and acute and convalescent status. Objective: We sought to quantitatively explore the relationship between FLG genotype, filaggrin breakdown products (natural moisturizing factor [NMF]), and corneocyte morphology in patients with AD. Methods: We studied 15 children at first presentation of AD and after 6 weeks of standard therapy. We applied atomic force microscopy to study corneocyte conformation in patients with AD stratified by FLG status and NMF level. By using a new quantitative methodology, the number of VPs per investigated corneocyte area was assessed and expressed as the Dermal Texture Index score. Corneocytes were also labeled with an anticorneodesmosin antibody and visualized with scanning electron microscopy. Results: We found a strong correlation between NMF levels and Dermal Texture Index scores in both acute and convalescent states (respective r 52 0.80 and 20.75, P < .001 and P 5 .002). Most, but not all, VPs showed the presence of corneodesmosin abundantly all over the cell surface in homozygous/compound heterozygous FLG patients and, to a lesser extent, in heterozygous and wild-type patients. Conclusions: NMF levels are highly correlated with corneocyte morphology in patients with AD. These corneocyte conformational changes shed further insight into the filaggrindeficient phenotype and help explain the barrier defect in patients with AD with FLG LOF mutations. (J Allergy Clin Immunol 2015;nnn:nnn-nnn.)

The effect of 2-nonyl-1,3-dioxolane (SEPA™) on the structure of human stratum corneum was investigated by FT-IR spectroscopy at variable temperature, differential scanning calorimetry and scanning electron microscopy. A significant influence of SEPA™ treatment on position and intensity of IR absorption bands and DSC thermal transitions of SC lipids was detected. An appreciable loosening of SC cell packing was also observed by SEM analysis. These modifications are reversed after SEPA™ is removed from the site of application. The results clearly demonstrate that SEPA™ is able to modify the structure of the lipid matrix in which corneocytes are embedded, thus suggesting a possible use of SEPA™ to increase the permeability of the stratum corneum to lipophilic drugs.

X-ray diffraction analysis was done on the membrane couplets isolated from newborn mouse stratum corneum. The same lipid reflections were observed for whole stratum corneum and couplets, adding further support to the thesis that stratum corneum lipid is intercellular in location rather than associated with the intracellular filamentous protein.

Bloor1 has shown relationships between physiological activity and the nature of the lipids in various tissues of the animal body. A high degree of activity is paralleled by a high phospholipid to cholesterol ratio. Since cells of the epidermis undergo a marked change in physiological activity during keratinization, we determined some of the lipids in epidermal cells before and after this process. The epidermis was separated from the cutis by digesting the skin, from which all subcutaneous fat had been removed, in cold 1% acetic acid. The completeness of the separation was confirmed by microscopic examination of sections of the skin. Several samples of epidermis were analyzed separately. Since it was impossible to obtain sufficiently large samples composed entirely of stratum germinativum, material containing considerable but varying quantities of this layer of active cells was scraped from the proximal surface of the epidermis and analyzed. Samples composed entirely of stratum corneum, trimmed from the so...

• We encountered a patient with continual skin peeling syndrome, a rare disorder in which generalized, noninflammatory exfoliation of the stratum corneum occurs. Although scaling occurred spontaneously in our patient, he was also able to manually peel sheets of skin without bleeding or pain. Histologically, there was separation of corneocytes above the granular cell layer. Ultrastructural examination revealed an unusual type of intracellular cleavage, in which the plasma membrane of the "peeling" cell remained firmly adherent to the underlying cell while the upper part of the cell exfoliated. Unique intercellular electron-dense globular deposits were localized to the stratum corneum. ( Arch Dermatol 1986;122:71-75)

Using a suitable histochemical method vitamins D and 7-dehydrocholesterol could be shown into the epidermis of several mammal species. As the histochemical method used is able to discriminate vitamins D and 7-dehydrocholesterol from cholesterol and its esters, the sites where these vitamins were synthesized within the epidermis layers could be established. Vitamins D and 7-dehydrocholesterol were found into the epidermis in the same sites where cholesterol and its esters take place, such as: the keratinizing cell thick membrane and the stratum spinosum and stratum granulosum keratinocytes cytoplasm. Inside the keratinocyte cytoplasm vitamin D shows a granular pattern and appears weakly bound to proteins. The reactivity of such granules seems to be partially blocked as could be shown by an hydrolysis accomplished previously. After the hydrolysis reactive vitamin D was also found inside the epidermis intercellular space. The results suggest that vitamin D is synthesized into the cytoplasm of stratum spinosum and stratum granulosum keratinocytes, where it appears weakly bound to proteins. Afterwards it reaches the intercellular space, where its synthesis is accomplished and it becomes firmly protein-bound losing its histochemical reactivity. However, after a suitable hydrolysis the histochemical reactivity could be recovered. From the intercellular spaces vitamin D could take 2 fates: It was partially incorporated on the keratinizing cell thick membrane out surface and eliminated by means of the epidermis exfoliation. It was partially absorbed after passing across the basement membrane. On the other hand, the vitamin D placed inside the stratum spinosum and stratum granulosum keratinocytes cytoplasm become incorporated on the inner surface of the keratinizing cell thick membrane. The relationship between vitamin D biosynthesis and the epidermis lamellar bodies was discussed.

Summary Human epidermis contains a low molecular weight SH-protease inhibitor (Human Epidermal Inhibitor = HE1), whose epidermal localization was performed with the indirect immunofluorescence method. The fluorescence was most intensive in the cytoplasms of epidermal cells, often occurring perinuclearly. The fluorescent material in the frozen sections was often finely granular and occasionally extended outside the cytoplasm, while the fluorescence in fixed sections was more uniform, but weaker. Stratum basale generally stained poorly or not at all, as did also stratum lucidum. Stratum corneum stained fairly intensively throughout. In addition to fixation, the outcome of staining was also affected by the thickness of the epidermis, particularly stratum corneum. The significance of this inhibitor for the differentiation of epidermal cells and the keratinization of epidermis has therefore been discussed, and the authors assume it to be of considerable significance in these processes.

•Staphylococcus aureushas a peculiar ability to colonize the skin of patients with atopic dermatitis. We examined the possibility that this might be due to a specific ability of this pathogenic staphylococcus to adhere to atopic stratum corneum. We used an in vitro model to show thatS aureusdoes have an unusual ability to adhere to atopic corneocytes when compared with corneocytes obtained from patients with other cutaneous diseases, including psoriasis. Protein A—a component of the staphylococcal cell wall—may be responsible in part for this adherence phenomenon. This trait did not extend to the other gram-positive bacteria tested. (Arch Dermatol1986;122:166-169)

The process of epidermal cell renewal, differentiation, and shedding is an exquisitely well-balanced, smoothly functioning system in normal persons. Modern interest in the epidermis has focused primarily on rates and control of cell renewal and on the composition of keratin and keratohyalin polypeptides. Until recently, except for pharmacologic studies of percutaneous penetration, comparatively little consideration has been directed toward the stratum corneum as an organized tissue with cohesive forces that initially hold together its cells and later permit their orderly shedding as small, clinically inapparent bits of material. Yet excessive accumulation and retention of stratum corneum are clinically of great importance in patients with both generalized scaling dermatoses (eg, psoriasis and ichthyosis) and localized hyperplasias (eg, warts and calluses). RECESSIVE X-LINKED ICHTHYOSIS (RXLI) AND STEROID SULFATASE Although many pharmacologic agents are available for the treatment of hyperkeratosis, usually these are only modestly effective, and little is known about their mechanism

Cytological abnormalities of superficial horny cells from 266 patients with common parakeratotic and orthokeratotic diseases (psoriasis, seborrheic dermatitis, various types of dermatitis-eczema, mycosis fungoides, and several other dermatoses) were evaluated with an adhesive slide technique. Most patients showed orthokeratotic and parakeratotic (nucleated) corneocytes in varying frequency. Horny cells in different stages of nuclear decomposition (halo cells) and masses of leukocytes were observed in only some of these dermatoses. An analysis of the frequency of nucleated horny cells and halo cells yielded statistically significant differences between psoriasis and most other dermatoses; only seborrheic dermatitis of the head region and mycosis fungoides showed similar changes in some instances. These findings suggest a classification of cytological changes which may be useful in the differential diagnosis of these diseases, particularly in the cytodiagnosis of psoriasis.

Lesions and nearby normal skin in 31 patients with tinea versicolor were studied for (1) quantity and composition of microbial flora, (2) quantity of desquamating cells in the horny layer (corneocyte count), and (3) quantity of fungus and proportion of yeasts and filamentous forms. The bacterial species in the lesions were the usual cutaneous residents. Bacterial density was increased fourfold because of the increased surface. Corneocyte count was elevated and an increased rate of turnover was revealed by an eightfold increase in parakeratotic cells. In the lesions, filamentous forms were twice as numerous as yeast forms; on normal skin, yeasts were five times as numerous as filaments. Normal sites yielded more filaments than similar sites in normal subjects. This supports the concept that the cause of tinea versicolor is Pityrosporum orbiculare which becomes pathogenic when it changes from a yeast to a filamentous habitat.

The first line of defense of the human body against harmful agents such as toxic chemicals, viruses and bacteria is the stratum corneum (SC), the skin's outer layer. A simple “brick and mortar” analogy is often used to describe how the lipid matrix (the “mortar”) of the stratum corneum holds together keratin-rich and largely impenetrable corneocytes (the “bricks”). Primarily due to uncertainty in the molecular structure of the lipid matrix, the pathways of permeation of toxic chemicals or drugs administered transdermally are not completely understood. We’ve used molecular dynamics to simulate a multi-lamellae 30-nm cross-section of the lipid matrix, totaling nearly 1 million atoms, under varying conditions of acidity and salt concentration for more than two microseconds. During our simulations, the skin's lipids form spontaneously a multilamellar structure where small pockets of water are separated by regions of partial fusion between the lamellae. The simulations suggest a potential assembly mechanism of the SC having a delicate balance between the lipid, water and salinity contents, which we’ve interrogated further using our recently developed coarse grain parameters for ceramides and cholesterol. In addition to visualizing a key event in the assembly of the largest human organ, our results further clarify the criteria to develop new delivery vehicles for pharmaceutical treatment.