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Background There is currently no insight into biomarkers that can predict the onset of pediatric atopic dermatitis (AD). Methods Nested in a prospective birth cohort study that examined the occurrence of physician-diagnosed AD in 300 children, 44 random children with onset of AD in the first year of life were matched on sex and season of birth with 44 children who did not develop AD. Natural moisturizing factor (NMF), corneocyte surface protrusions, cytokines, free sphingoid bases (SBs) of different chain lengths and their ceramides were analyzed from tape strips collected at 2 months of age before onset of AD using liquid chromatography, atomic force microscopy, multiplex immunoassay, and liquid chromatography mass spectrometry, respectively. Results Significant alterations were observed for four lipid markers, with phytosphingosine ([P]) levels being significantly lower in children who developed AD compared with children who did not (median 240 pmol/mg vs. 540 pmol/mg, p < 0.001). The two groups of children differed in the relative amounts of SB of different chain lengths (C17, C18 and C20). Thymus- and activation-regulated chemokine (TARC/CCL17) was slightly higher in children who developed AD, whereas NMF and corneocyte surface texture were similar. AD severity assessed by the eczema area and severity index (EASI) at disease onset was 4.2 (2.0;7.2). [P] had the highest prediction accuracy among the biomarkers (75.6%), whereas the combination of 5 lipid ratios gave an accuracy of 89.4%. Conclusion This study showed that levels and SB chain length were altered in infants who later developed AD, and that TARC/CCL17 levels were higher.

Traveling to space puts astronauts at risk of developing serious health problems. Of particular interest is the skin, which is vitally important in protecting the body from harmful environmental factors. Although data obtained from long-duration spaceflight studies are inconsistent, there have been indications of increased skin sensitivity and signs of dermal atrophy in astronauts. To better understand the effects of spaceflight stressors including microgravity, ionizing radiation and psychological stress on the skin, researchers have turned to in vitro and in vivo simulation models mimicking certain aspects of the spaceflight environment. In this review, we provide an overview of these simulation models and highlight studies that have improved our understanding on the effect of simulation spaceflight stressors on skin function. Data show that all aforementioned spaceflight stressors can affect skin health. Nevertheless, there remains a knowledge gap regarding how different spaceflight stressors in combination may interact and affect skin health. In future, efforts should be made to better simulate the spaceflight environment and reduce uncertainties related to long-duration spaceflight health effects. ispartof: BIOMEDICINES vol:10 issue:2 ispartof: location:Switzerland status: published

Background: The pathogenesis underlying keloid formation is still poorly understood. Research has focused mostly on dermal abnormalities, while the epidermis has not yet been studied. Objectives: To identify differences within the epidermis of mature keloid scars compared with normal skin and mature normotrophic and hypertrophic scars. Methods: Rete ridge formation and epidermal thickness were evaluated in tissue sections. Epidermal proliferation was assessed using immunohistochemistry (Ki67, keratins 6, 16 and 17) and with an in vitro proliferation assay. Epidermal differentiation was evaluated using immunohistochemistry (keratin 10, involucrin, loricrin, filaggrin, SPRR2, SKALP), reverse-transcriptase polymerase chain reaction (involucrin) and transmission electron microscopy (stratum corneum). Results: All scars showed flattening of the epidermis. A trend of increasing epidermal thickness correlating to increasing scar abnormality was observed when comparing normal skin, normotrophic scars, hypertrophic scars and keloids. No difference in epidermal proliferation was observed. Only the early differentiation marker involucrin showed abnormal expression in scars. Involucrin was restricted to the granular layer in healthy skin, but showed panepidermal expression in keloids. Normotrophic scars expressed involucrin in the granular and upper spinous layers, while hypertrophic scars resembled normotrophic scars or keloids. Abnormal differentiation was associated with ultrastructural disorganization of the stratum corneum in keloids compared with normal skin. Conclusions: Keloids showed increased epidermal thickness compared with normal skin and normotrophic and hypertrophic scars. This was not due to hyperproliferation, but possibly caused by abnormal early terminal differentiation, which affects stratum corneum formation. Our findings indicate that the epidermis is associated with keloid pathogenesis and identify involucrin as a potential diagnostic marker for abnormal scarring.

Oral folate fortification has been successful in many developed nations, however, developing countries still face low compliance and high incidence of folate deficiency associated with low birth weight infants and preterm deliveries. We report safe and efficient approach for transdermal systemic folate delivery using fluidising liposomes (120 ± 4 nm) stabilised within 3D matrix of naturally occurring cosmetic bases: Fuller’s earth and henna with room temperature stability. The proof of stratum corneum fluidisation was established ex-vivo by Langmuir-Blodgett film, FTIR and confocal imaging in rat skin. In-vivo topical application in rats showed 11-fold increase in plasma folate within 2 hr, confirming systemic delivery through skin. Efficacy study in folate deficient rats over 4 weeks showed significantly higher plasma levels compared to oral delivery with significant skin depot. Sub-acute toxicity studies in rats at 750-fold higher doses showed safety after 4 weeks daily application. Primary irritation patch test on 25 healthy human volunteers proved non-irritant nature of the nutricosmetics. The technology is first demonstration of transdermal folate fortification with nanosized liposome incorporated in cosmetics, without synthetic surfactants/ethanol or need of external energy. The platform technology opens the possibility of delivering multiple nutrients systemically through skin and can be scaled for affordable community fortification.

We are grateful to Pierre Lanteri and Yohann Clement for their help with the statistical analyses. We would also like to thank Helene Wong and Jose Serrano for their collaboration to this project.; International audience; The skin toxicity of four ionic surfactants and fourteen non-ionic surfactants was investigated so as to disclose structure/toxicity relationships. The skin toxicity was assessed by means of four in vitro assays, MU and LDH test of cell viability, and detection of the inflammation markers IL-1 alpha. and IL-8. Several descriptors of the physicochemical properties of the surfactants were measured in order to find out those molecular descriptors that correlate with the toxicity measured on skin. Principal component analysis and analysis of the matrix of Pearson's correlation coefficients were used for the search of the molecular descriptors having the highest relevance. There was a definite difference between ionic and non-ionic surfactants. Ionic surfactants are the most toxic if they are soluble in water. Crystalline ionic surfactants of low solubility show low toxicity. The sign of the charge, anionic or cationic, does not matter. The value of the CMC that has been put forward as a highly relevant parameter does not account for the full skin toxicities observed; the CMC of non-ionic surfactants is not a parameter of relevance. For non-ionic surfactants, the nature of the chemical bond linking the polar head group and the alkyl chain has a significant impact on skin toxicity; PEG ethers appear more toxic than PEG esters. The results revealed the mildness of polyoxyethylene sorbitan esters whatever be their alkyl chain length. On the other hand, for sucrose ester surfactants, C12 alkyl length resulted in the greatest skin toxicity. Since the molecular parameters of ionic, non-ionic, water-soluble and crystalline surfactants are different, a universal parameter was introduced, the order parameter describing the orientation ordering of surfactant molecules at interfaces. The highly ordered organization of crystalline surfactants associated with their low solubility in water makes them very low-irritant surfactants.

Summary Cornification and epidermal barrier defects are associated with a number of clinically diverse skin disorders. However, a suitable in vitro model for studying normal barrier function and barrier defects is still lacking. Here, we demonstrate the generation of human epidermal equivalents (HEEs) from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). HEEs are structurally similar to native epidermis, with a functional permeability barrier. We exposed a pure population of hESC/iPSC-derived keratinocytes, whose transcriptome corresponds to the gene signature of normal primary human keratinocytes (NHKs), to a sequential high-to-low humidity environment in an air/liquid interface culture. The resulting HEEs had all of the cellular strata of the human epidermis, with skin barrier properties similar to those of normal skin. Such HEEs generated from disease-specific iPSCs will be an invaluable tool not only for dissecting molecular mechanisms that lead to epidermal barrier defects but also for drug development and screening., Highlights • Manufacture of HEEs with a functional epidermal barrier in vitro from hESCs/iPSCs • Unique model for skin diseases with defective epidermal permeability barriers • Easily adaptable model for use in regenerative and aesthetic medicine • Cost-effective model for testing new drugs and cosmetics, Ilic, Mauro, and colleagues describe the manufacture of in vitro human epidermal equivalents (HEEs) from human embryonic stem cells (hESCs) and pluripotent stem cells (iPSCs). The HEEs have cellular strata and apparently normal barrier properties as seen in the intact human epidermis. Thus, they represent a unique in vitro system for investigating diseases caused by defective epidermal permeability barriers, and provide a model for testing new drugs and cosmetics.

In multicellular organisms, cells adopt various shapes, from flattened sheets of endothelium to dendritic neurons, that allow the cells to function effectively. Here, we elucidated the unique shape of cells in the cornified stratified epithelia of the mammalian epidermis that allows them to achieve homeostasis of the tight junction (TJ) barrier. Using intimate in vivo 3D imaging, we found that the basic shape of TJ-bearing cells is a flattened Kelvin's tetrakaidecahedron (f-TKD), an optimal shape for filling space. In vivo live imaging further elucidated the dynamic replacement of TJs on the edges of f-TKD cells that enables the TJ-bearing cells to translocate across the TJ barrier. We propose a spatiotemporal orchestration model of f-TKD cell turnover, where in the classic context of 'form follows function', cell shape provides a fundamental basis for the barrier homeostasis and physical strength of cornified stratified epithelia. DOI: http://dx.doi.org/10.7554/eLife.19593.001, eLife digest The skin surface – known as the epidermis – is made up of sheets of cells that are stacked up in layers. One of the roles of the skin is to provide a protective barrier that limits what leaks into or out of the body. A particular layer of the epidermis – referred to as the stratum granulosum – is primarily responsible for forming this barrier. The cells in this layer are sealed together in a zipper-like fashion by structures known as tight junctions. New skin cells are continuously produced in the lowest cell layers of the epidermis, and move upwards to integrate into the stratum granulosum layer to replace old cells (which also move upwards to leave the layer). How stratum granulosum cells are replaced without disrupting the tight junction barrier was not well understood. Yokouchi et al. used a technique called confocal microscopy to examine the stratum granulosum cells in the ears of mice, and found that the shape of these cells forms the basis of the barrier that they form. These cells resemble a flattened version of a shape called Kelvin’s tetrakaidecahedron: a 14-sided solid with six rectangular and eight hexagonal sides. This structure was proposed by Lord Kelvin in 1887 to be the best shape for filling space. Tight junctions are present on the edges of the flattened Kelvin’s tetrakaidecahedron. Further experiments revealed that the tight junctions move from cell to cell in a spatiotemporally-coordinated manner in order to maintain a continuous barrier throughout the stratum granulosum as cells are replaced. A newly formed stratum granulosum cell appears beneath the cell that it will replace. The shape of these cells enables a new barrier of three-way tight junction contacts to form between them and the neighboring cells in the stratum granulosum. After this barrier has formed, the upper cell leaves the stratum granulosum. Future research could address how cells adopt the flattened Kelvin’s tetrakaidecahedron shape, and discover why tight junctions only form in one layer of the epidermis. DOI: http://dx.doi.org/10.7554/eLife.19593.002

Background Filaggrin, which is encoded by the filaggrin gene (FLG), is an important component of the skin's barrier to the external environment, and genetic defects in FLG strongly associate with atopic dermatitis (AD). However, not all patients with AD have FLG mutations. Objective We hypothesized that these patients might possess other defects in filaggrin expression and processing contributing to barrier disruption and AD, and therefore we present novel therapeutic targets for this disease. Results We describe the relationship between the mechanistic target of rapamycin complex 1/2 protein subunit regulatory associated protein of the MTOR complex 1 (RAPTOR), the serine/threonine kinase V-Akt murine thymoma viral oncogene homolog 1 (AKT1), and the protease cathepsin H (CTSH), for which we establish a role in filaggrin expression and processing. Increased RAPTOR levels correlated with decreased filaggrin expression in patients with AD. In keratinocyte cell cultures RAPTOR upregulation or AKT1 short hairpin RNA knockdown reduced expression of the protease CTSH. Skin of CTSH-deficient mice and CTSH short hairpin RNA knockdown keratinocytes showed reduced filaggrin processing, and the mouse had both impaired skin barrier function and a mild proinflammatory phenotype. Conclusion Our findings highlight a novel and potentially treatable signaling axis controlling filaggrin expression and processing that is defective in patients with AD., Graphical abstract

Every optical imaging technique is limited in its penetration depth by scattering occurring in biological tissues. Possible solutions to overcome this problem consist of limiting the detrimental effects of scattering by reducing optical inhomogeneities within the sample. This can be achieved either by using physical methods (such as refractive index matching solutions) or by chemical methods (such as the removal of scatterers), based on tissue transformation protocols. This review provides an overview of the current state-of-the-art methods used for both ex-vivo and in-vivo optical clearing of biological tissues. We start with a brief history of the development of the most widespread clearing methods across the new millennium, then we describe the working principles of both physical and chemical methods. Clearing methods are then reviewed, pointing the attention of the reader on both physical and chemical methods, classified based on the tissue size and type for each specific application. A small section is reserved for methods that have already found in-vivo applications at the research level. Finally, a detailed discussion highlighting both the most relevant results achieved and the new ongoing developments in this field is reported in the last part, together with future perspectives for the clearing methodology. (C) 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Background: The skin barrier acts as the first line of defense against constant exposure to biological, microbial, physical and chemical environmental stressors. Dynamic interplay between defects in the skin barrier, dysfunctional immune responses, and environmental stressors are major factors in the development of atopic dermatitis (AD). A systems-biology modeling approach can yield significant insights into these complex and dynamic processes through integration of prior biological data. Objective: To develop a multi-scale mathematical model of AD pathogenesis that describes the dynamic interplay between the skin barrier, environmental stress and immune dysregulation, and use it to achieve a coherent mechanistic understanding of onset, progression and prevention of AD. Methods: We mathematically investigated synergistic effects of known genetic and environmental risk factors on the dynamic onset and progression of the AD phenotype, from a mostly asymptomatic mild phenotype to a severe treatment-resistant form. Results: Our model analysis identified a “double switch”, with two concatenated bistable switches, as a key network motif that dictates AD pathogenesis: The first switch is responsible for the reversible onset of inflammation; The second switch is triggered by long-lasting or frequent activation of the first switch, causing the irreversible onset of systemic Th2 sensitization and worsening of AD symptoms. Conclusions: Our mathematical analysis of the bistable switch predicts that genetic risk factors lower the threshold of environmental stressors to trigger systemic Th2 sensitization. This analysis predicts and explains four common clinical AD phenotypes from a mild and reversible phenotype through to severe and recalcitrant disease and provides a mechanistic explanation for clinically-demonstrated preventive effects of emollient treatments against development of AD.

Caspase-14 is a unique member of the evolutionarily conserved family of cysteinyl aspartate–specific proteinases, which are mainly involved in inflammation and apoptosis. However, recent evidence also implicates these proteases in proliferation and differentiation. Although most caspases are ubiquitously expressed, caspase-14 expression is confined mainly to cornifying epithelia, such as the skin. Moreover, caspase-14 activation correlates with cornification, indicating that it plays a role in terminal keratinocyte differentiation. The determination of in vitro conditions for caspase-14 activity paved the way to identifying its substrates. The recent development of caspase-14–deficient mice underscored its importance in the correct degradation of (pro)filaggrin and in the formation of the epidermal barrier that protects against dehydration and UVB radiation. Here, we review the current knowledge on caspase-14 in skin homeostasis and disease.

Sodium soap fibers with varying alkyl chain lengths were studied by cryotransmission electron microscopy and differential scanning calorimetery in water and water-propylene glycol mixtures. The morphology of the lamellar fibers was found to be dependent on the chain length of the alkyl chain and the solvent polarity. Cryoelectron microscopy revealed that short-chain (C-10-C-14) sodium soaps have the bilayer plane perpendicular to the fiber width, which enables one to see the bilayer striations on the fibers, whereas long-chain (C-16-C-20) sodium soaps have bilayer planes parallel to the fiber width, and the bilayer striations are not visible. This change in morphology is accompanied by a change in dissolution enthalpy.

Background: Palmoplantar keratodermas (PPK) encompass a large genetically heterogeneous group of diseases associated with hyperkeratosis of the soles and/or palms that occur either isolated or in association with other cutaneous and extracutaneous manifestations. Pathogenic mutations in the desmoglein 1 gene (DSG1) have recently been identified in a subset of patients with the striate type of PPK. Observation: We have identified a patient with a focal non-striated form of PPK associated with discrete troubles of keratinisation at sites exposed to mechanical trauma, such as the knees, ankles or finger knuckles, and with mild nail dystrophy. Genetic analyses disclosed a novel dominantly inherited heterozygous single base insertion in exon 3 of DSG1, 121insT, leading to a premature termination codon. The mutation was also present in the father and in a sister. Conclusion: Our observation extends the spectrum of clinical features associated with genetic defects in DSG1 and provides further evidence that perturbation of desmoglein 1 expression has a critical impact on the integrity of tissues experiencing strong mechanical stress.

The objective of the present study is to evaluate the efficacy and the safety of transdermal iontophoretic delivery of Rapomorphine, a potent dopamine agonist, in combination with surfactant pretreatment in patients with advanced Parkinson's disease. Iontophoresis patches were applied in 16 patients for 3.5 h, with 0.5 h of passive delivery followed by 3 h Of Current application at a current density of 250 mu A/cm(2). Eight of these patients were treated with a surfactant formulation prior to iontophoresis. The pharmacokinetics, pharmacodynamic effects, systemic and local side effects of R-apomorphine were assessed. The plasma concentration vs. time profiles upon iontophoresis of R-apomorphine were described successfully by a novel pharmacokinetic model. The model suggests that only 1.9% of the dose that has been released from the patch accumulated in the skin. The patients treated with the surfactant formulations showed a statistically significant increase of bioavailability (from 10.6 +/- 0.8% to 13.2 +/- 1.4%) and of the steady state input rate (from 75.3 +/- 6.6 to 98.3 +/- 12.1 nmol/cm(2) h) compared to the control patients (iontophoresis without absorption enhancers). In five out of eight patients in the study group and in three out of eight patients in the control group, clinical improvement was observed. (c) 2004 Elsevier B.V. All rights reserved.

Opto-thermal transient emission radiometry(OTTER) is a infrared remote sensing technique, which has been successfully used in in vivo skin moisture content and skin moisture depth profiling measurements.In present paper, we extend this moisture content measurement capability to analyze the moisture content of fruit (tomato, grape, etc.) skins, and to study the relationship between fruits ripening process and their surface moisture and moisture depth profiles

Optothermal transient emission radiometry (OTTER) was used to determine the mean surface hydration and the hydration profile of three mutants (beefsteak, slicing and salad) of harvested tomatoes (Lycopersicon esculentum) that were kept under ambient conditions for as long as 51 days. Maximal sensitivity of OTTER to water in the samples was achieved by using 2.94 m and 13.1 m as excitation and emission wavelengths, respectively. The surface hydration increases rapidly and reaches a constant level during the remaining period. The hydrolysis of pectic substances that occur in tomatoes while ripening might be a possible cause for the observed change in hydration. PACS 81.70.Cr; 39.30.+w; 87.14.-g; 78.47.+p

Hypertrophic scars and keloids resulting from surgery, burns, trauma and infection can be associated with substantial physical and psychological distress. Various non-invasive and invasive options are currently available for the prevention and treatment of these scars. Recently, an international multidisciplinary group of 24 experts on scar management (dermatologists; plastic and reconstructive surgeons; general surgeons; physical medicine, rehabilitation and burns specialists; psychosocial and behavioural researchers; epidemiologists; beauticians) convened to update a set of practical guidelines for the prevention and treatment of hypertrophic and keloid scars on the basis of the latest published clinical evidence on existing scar management options. Silicone-based products such as sheets and gels are recommended as the gold standard, first-line, non-invasive option for both the prevention and treatment of scars. Other general scar preventative measures include avoiding sun exposure, compression therapy, taping and the use of moisturisers. Invasive treatment options include intralesional injections of corticosteroids and/or 5-fluorouracil, cryotherapy, radiotherapy, laser therapy and surgical excision. All of these options may be used alone or as part of combination therapy. Of utmost importance is the regular re-evaluation of patients every four to eight weeks to evaluate whether additional treatment is warranted. The amount of scar management measures that are applied to each wound depends on the patient's risk of developing a scar and their level of concern about the scar's appearance. The practical advice presented in the current guidelines should be combined with clinical judgement when deciding on the most appropriate scar management measures for an individual patient.

Background : Although assessment of glycated nail proteins may be a useful marker for monitoring of diabetes, their nature and formation are still poorly understood. Besides a detailed anatomical analysis of keratin glycation, the usefulness of glycated nail protein assessment for monitoring diabetic complications was investigated. Methods : 216 patients (94 males, 122 females; mean age +/- standard deviation: 75.0 +/- 8.7 years) were enrolled. Glycation of nail and eye lens proteins was assessed using a photometric nitroblue tetrazolium-based assay. Following chromatographic separation of extracted nail proteins, binding and nonbinding fractions were analyzed using one-dimensional gel electrophoresis. Using a hand piece containing a latch-type-bur, a meticulous cutting of the nail plate into superficial and deep layers was performed, followed by a differential analysis of fructosamine. Results : Using SDS PAGE, four and two bands were identified among the nonglycated and glycated nail fraction respectively. Significantly lower fructosamine concentrations were found in the superficial nail layer (mean: 2.16 +/- 1.37 mu mol/g nails) in comparison with the deep layer (mean: 4.36 +/- 2.55 mu mol/g nails) (P

Intensive interest is currently focused on the role of ceramide (1), a key lipid molecule that functions as a second messenger. The first asymmetric synthesis of a D-erythro-ceramide analogue that contains a C(5)-C(6) trans double bond (3), together with its biological evaluation in a viral-liposome fusion system, is described. Sharpless asymmetric dihydroxylation of 4'-methoxyphenyl trans-5-octadecyn-2-enyl ether (enyne 8a), prepared by the coupling reaction of 1-[(E)-(4'-bromo-2'-butenyl)oxy]-4-methoxybenzene (7) with Lithium tetradecyne, generated yne-diol 9 in 96% yield with the desired stereochemistry at the C(2)and (3) positions and high enantiomeric purity (95% enantiomeric excess). Birch reduction (Li/EtNH2) of yne-diol 9 furnished (2R,3R,5E)-octadecene-1,2,3-triol (10) stereospecifically. The latter was converted to 2 azido derivative 13 in three steps (via a 2-O-triflate-1,3-O-benzylidene intermediate) and 55% overall yield. Reduction of azide 13 and in situ N-acylation with p-nitrophenyl cis-hexadec-4-enoate provided D-erythro-Delta(5)-trans-ceramide (3) in 91% yield. The role of the trans double bond of ceramide in mediating fusion of an alphavirus (Semliki Forest virus) was assessed in a liposomal model system, using target phospholipid/cholesterol vesicles containing either D-erythro-ceramide 1 or 3. The kinetics of virus fusion, as monitored by a change in pyrene excimer fluorescence over a period of 60 s, showed that Delta(5)-trans-ceramide 3 was completely inactive, indicating that there is an absolute requirement for the trans double bond to be located between C(4) and C(5). These data indicate that the molecular determinants on the viral envelope glycoprotein are highly specific for recognition of the unsaturated site in the ceramide molecule.

2-Hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) and 2,6-dimethyl-beta-cyclodextrin (D-beta-CyD) were studied for transdermal penetration enhancement of the cytochrome P450 inhibitor liarozole by an in-vivo transdermal absorption rat model. The mode of action of penetration enhancement was investigated by differential scanning calorimetry (DSC). In-vivo, HP-beta-CyD, as a 20% aqueous solution, increased the absorption of liarozole approximately threefold and a 20% aqueous solution of D-beta-CyD decreased the percutaneous absorption of liarozole in blood by a factor of 0.6. However, pretreatment with D-beta-CyD (20%, 4 h) enhanced the transdermal absorption 9.4-fold. In the DSC experiments the thermal profile of human stratum corneum was practically unchanged after treatment with HP-beta-CyD, but treatment with D-beta-CyD revealed an interaction of D-beta-CyD with the protein and lipid fraction. Thus the results from DSC and those from the permeability experiments revealed that D-beta-CyD acts as a transdermal absorption enhancer by changing the stratum corneum barrier whereas HP-beta-CyD influences the partitioning behaviour of the drug in the skin.

In this paper I first briefly look at diffusion in several controlled release devices. I have found that these exploit complicated diffusional mechanisms. These cannot be understood using the conventional description of diffusion. So, a general theory of multicomponent diffusion which can describe them is considered. An overview follows of the present knowledge on diffusivities of small and large permeants in dense polymers, swollen polymers, charged polymers, gels and porous media. The paper ends with a brief discussion of the limitations of diffusion theory in swelling polymers.

In this paper I first briefly look at diffusion in several controlled release devices. I have found that these exploit complicated diffusional mechanisms. These cannot be understood using the conventional description of diffusion. So, a general theory of multicomponent diffusion which can describe them is considered. An overview follows of the present knowledge on diffusivities of small and large permeants in dense polymers, swollen polymers, charged polymers, gels and porous media. The paper ends with a brief discussion of the limitations of diffusion theory in swelling polymers.

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. (c) 2009 Wiley Periodicals, Inc. Biopolymers 91: 1172-1181, 2009.

Opto-thermal transient emission radiometry(OTTER) is a infrared remote sensing technique, which has been successfully used in in vivo skin moisture content and skin moisture depth profiling measurements.In present paper, we extend this moisture content measurement capability to analyze the moisture content of fruit (tomato, grape, etc.) skins, and to study the relationship between fruits ripening process and their surface moisture and moisture depth profiles

The aim of the present study was to evaluate the in vitro antioxidant and in vivo photoprotective activities of a lyophilized extract of Capparis spinosa L. (LECS) obtained by methanolic extraction from the flowering buds of this plant. For the in vitro experiments, LECS was tested employing three different models: (a). bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical (DPPH test); (b). peroxidation, induced by the water-soluble radical initiator 2,2'-azobis(2-amidinopropane) hydrochloride, of mixed dipalmitoylphosphatidylcholine/linoleic acid unilamellar vesicles (LUVs) (LP-LUV test); and (c). UV-induced peroxidation of phosphatidylcholine multilamellar vesicles (UV-IP test). The in vivo antioxidant/radical scavenger activity was assessed by determining the ability of topically applied LECS to reduce UVB-induced skin erythema in healthy human volunteers. From the results obtained in in vitro and in vivo tests, LECS showed a significant antioxidant effect. Furthermore, by chromatographic fractionation and spectroscopic methods, we identified the major constituents of LECS, and particularly some flavonols (kaempferol and quercetin derivatives) and hydroxycinnamic acids (caffeic acid, ferulic acid, p-cumaric acid, and cinnamic acid).

2-Hydroxypropyl-β-cyclodextrin (HP-β-CyD) and 2,6-dimethyl-β-cyclodextrin (D-β-CyD) were studied for transdermal penetration enhancement of the cytochrome P450 inhibitor liarozole by an in-vivo transdermal absorption rat model. The mode of action of penetration enhancement was investigated by differential scanning calorimetry (DSC). In-vivo, HP-β-CyD, as a 20% aqueous solution, increased the absorption of liarozole approximately threefold and a 20% aqueous solution of D-β-CyD decreased the percutaneous absorption of liarozole in blood by a factor of 0·6. However, pretreatment with D-β-CyD (20%, 4 h) enhanced the transdermal absorption 9·4-fold. In the DSC experiments the thermal profile of human stratum corneum was practically unchanged after treatment with HP-β-CyD, but treatment with D-β-CyD revealed an interaction of D-β-CyD with the protein and lipid fraction. Thus the results from DSC and those from the permeability experiments revealed that D-β-CyD acts as a transdermal absorption enhancer by changing the stratum corneum barrier whereas HP-β-CyD influences the partitioning behaviour of the drug in the skin.

Diffusivities have been determined for the drug clenbuterol for three non-sink, diffusional problems: diffusion out of a polymer matrix, diffusion through excised, human stratum corneum, and the combined case of diffusion out of a polymer matrix through contiguous, excised stratum corneum. Numerical solution of the diffusion equation for these problems yields theoretical values of drug mass in the acceptor phase, m a ( t ) th , vs time. Diffusion was then measured experimentally and the best value for diffusivity obtained by comparing the values of drug mass in the acceptor phase, m a ( t ) exp , with the corresponding m a ( t ) th data. In this fashion it was possible to obtain diffusivities for diffusion out of the polymer matrix for various values of drug loading and matrix thickness. For the problem of diffusion through stratum corneum a value for the partition coefficient of clenbuterol as well as for its diffusivity could be determined. The two diffusivities obtained for the combined model (i.e., D m within the matrix and D s within the stratum corneum) agree quite well with those obtained for the two separate problems, but are more scattered. Partition coefficients could not be accurately determined for diffusion out of the matrix or the combined problem.

Human body is perpetually subjected to environmental exposures as sun, natural, urban or industrial pollutions and societal exposures. Skin is the main physiological barrier facing to these different stresses; however its response mechanisms are still not well understood. Skin models are thus necessary to understand skin physiology and behavior in normal conditions or under stress. Because of the large natural interindividual variability and of some difficulties in obtaining human skin biopsies, we have been developing and characterizing different skin models such as reconstructed epidermis in vitro, native pigskin and human keratinocyte cells. These models allow us to study the mechanisms involved in ion homeostasis in correlation with structural organization and biological responses. In the present study, we have characterized the pig ear skin model using micro-particle induced x-ray emission (PIXE) analysis with the aim of evaluating the distribution of inorganic ions under normal or stress conditions together with the transepidermal penetration of external agents, such as aluminum oxides. The nuclear microprobe analysis allowed us to validate the culture conditions of the tissue and we have shown an alteration of the inorganic ion patterns after exposure to a chemical compound (sodium dodecyl sulfate) known for its deleterious effects on the barrier function. Finally, we have shown no transepidermal penetration of aluminum oxides after different exposures to cosmetic formulations. Copyright (C) 2009 John Wiley & Sons, Ltd.