Human Skin Ageing

Malassezia furfur was the first species described within the cosmopolitan yeast genus Malassezia, which now comprises 13 species. Reported isolation rates of these species from healthy and diseased human skin show geographic variations. PCR-fingerprinting with the wild-type phage M13 primer (5 0 -GAGGGTGGCGGTTCT-3 0 ) was applied to investigate phylogeographic associations of M. furfur strains isolated from Scandinavians residing permanently in Greece, in comparison to clinical isolates from Greek, Bulgarian and Chinese native residents. Seven M. furfur strains from Scandinavians were compared with the Neotype strain (CBS1878), CBS global collection strains (n ¼ 10) and clinical isolates from Greece (n ¼ 4), Bulgaria (n ¼ 15) and China (n ¼ 6). Scandinavian, Greek and Bulgarian M. furfur strains mostly formed distinct group clusters, providing initial evidence for an association with the host's geographical origin and with the underlying skin condition. These initial data address the hypothesis that M. furfur could be a eukaryotic candidate eligible for phylogeographic studies.

Based on two successfully completed ECVAM validation studies for in vitro skin corrosion testing of chemicals, the National Co-ordinators of OECD Test Guideline Programme endorsed in 2002 two new test guidelines: TG 430 'Transcutaneous Electrical Resistance assay' and TG 431 'Human Skin Model Test'. To allow all suitable in vitro human reconstructed (dermal or epidermal) models to be used for skin corrosion testing, the OECD TG 431 defines general and functional conditions that the model must meet before it will be routinely used for skin corrosion testing. In addition, the guideline requires correct prediction of 12 reference chemicals and assessment of intra- and inter-laboratory variability. To show that the OECD TG 431 concept works, in 2003 ZEBET tested several chemicals from the ECVAM validation trials on the SkinEthic reconstituted human epidermal (RHE) model. Based on knowledge that reconstructed human skin models perform similarly in toxicological studies, i...

The study aims to analyze the ef ect of the Body Surface Area (BSA) on the thermal comfort of university students. The study involved a survey to collect the weight, height, and body temperature of respondents. The survey also collected the respondents’ thermal response to their environment. The survey was carried out at the Faculty of Engineering, Khairun University, Ternate, and North Maluku Province, Indonesia. A total of 180 students, from the age of 20-25 years consisting of 143 men and 37 women have participated in this study. However, 30 students are excluded from the analyses due to their body temperature exceed 37.2 °C. Generally, the women body size is relatively larger than the man. The average weight and height for adult males are 60 kg and 164.62 cm, and females are 63 kg and 158.97 cm. The average body temperature of males was 36.7 °C and females was 36.25 °C. Most of the respondents (more than 80%) felt either warm or hot. There is a linear correlation between the Body Surface Area (BSA) and the thermal sensation vote (TSV) of respondents. Respondents with larger size of body surface tend to feel hotter than the ones with smaller size of body surface.

Background: To meet the challenge of an aging population, providers and payors must optimize chronic wound care outcomes and contain costs. Objective: To explore the costs, outcomes, and effects of outcomes on costs of pressure and venous ulcer woundcare protocols. Design: Modeling study using outcomes from a literature review. Methods: The cost of 12 weeks of wound care was modeled for a hypothetical managed-care plan. This included 100 000 covered lives and used a peer-validated wound care protocol. Only modalities with a pooled evidence base of at least 100 wounds were used to populate the model. Costs excluded supportive treatments. Results: 26 studies of three pressure ulcer protocols (n = 519) and three venous ulcer protocols (n = 883) qualified for inclusion in the models. After 12 weeks, the weighted average proportion of ulcers healed, and cost per ulcer healed, ranged from 48 to 61% and from $US910 to $US2179 (2000 values) for pressure ulcers, and from 39 to 51% and $US1873 to $US15 053 for venous ulcers. For a hypothetical managed-care plan, the difference between the least and most costeffective modalities was $US1.9 million for pressure ulcers and $US5.8 million for venous ulcers. Observed differences were generally attributable to variances in outcomes and cost differences related to frequency of dressing changes. Pressure ulcer care takes place in inpatient care settings; venous ulcers are managed on an outpatient basis. Physician visit frequencies are once every four weeks for pressure ulcers and once each week for venous ulcers. Wound sizes ranged from 2.5cm 2 to 5.6cm 2 for pressure ulcers and 5.4cm 2 to 10cm 2 for venous ulcers. All patients with pressure ulcers required pressure relief, nutritional support and incontinence management; venous ulcers required gradient compression. Costs per patient healed were lowest for pressure ulcers with hydrocolloids and highest ORIGINAL RESEARCH ARTICLE

Cumulative long-term exposure to solar ultraviolet radiation promotes premature skin aging characterized by wrinkle formation and reduced skin elasticity. In this study, we assessed whether microfat transfer could improve dermal and subcutaneous tissue thickness loss associated with photoaging. Twenty-one patients affected by facial photoaging (photodamage grade II–IV; age range 35–62 years; 19 females, 2 males; all of Caucasian origin) were treated using minimally invasive autologous dermal white fat transfer harvested with a recently designed microcannula. The results were determined by clinical assessment and patient self-evaluation and quantified by the Antera 3D® dermal digital device for noninvasive, objective, reliable, and accurate assessment of facial skin texture, color, and wrinkle characteristics. Compared with the pretreatment condition, the increment in soft tissue volume and improvement in skin quality and texture were assessed by a dermatologist after treatment. In addition, instrumental evaluation by digital skin profilometry of the treated areas revealed a 41% reduction in average wrinkle depth (7.29 ± 1.04 × 10−2 mm pretreatment vs. 4.31 ± 1.16 × 10−2 mm at 90 days posttreatment; p < 0.001), improved skin texture, more homogeneous and uniform skin color, and declined facial hemoglobin and melanin concentrations. The majority of patients (above 90%) reported improvements in self-perception. No significant complications were reported throughout the study. In conclusion, by using digital profilometry analysis as an objective and innovative tool to determine the outcome of treatment, we demonstrated that autologous microfat transfer is a safe and well-tolerated procedure with measurable beneficial effects on facial skin aging.

Pomegranate (Punica granatum) is an ancient fruit with exceptionally rich ethnomedical applications. The peel (pericarp) is well regarded for its astringent properties; the seeds for conferring invulnerability in combat and stimulating beauty and fertility. Here, aqueous fractions prepared from the fruit&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s peel and fermented juice and lipophilic fractions prepared from pomegranate seeds were examined for effects on human epidermal keratinocyte and human dermal fibroblast function. Pomegranate seed oil, but not aqueous extracts of fermented juice, peel or seed cake, was shown to stimulate keratinocyte proliferation in monolayer culture. In parallel, a mild thickening of the epidermis (without the loss of ordered differentiation) was observed in skin organ culture. The same pomegranate seed oil that stimulated keratinocyte proliferation was without effect on fibroblast function. In contrast, pomegranate peel extract (and to a lesser extent, both the fermented juice and seed cake extracts) stimulated type I procollagen synthesis and inhibited matrix metalloproteinase-1 (MMP-1; interstitial collagenase) production by dermal fibroblasts, but had no growth-supporting effect on keratinocytes. These results suggest heuristic potential of pomegranate fractions for facilitating skin repair in a polar manner, namely aqueous extracts (especially of pomegranate peel) promoting regeneration of dermis, and pomegranate seed oil promoting regeneration of epidermis.

Skin is a widely used route of delivery for local and systemic drugs and is potentially a route for their delivery as nanoparticles. The skin provides a natural physical barrier against particle penetration, but there are opportunities to deliver therapeutic nanoparticles, especially in diseased skin and to the openings of hair follicles. Whilst nanoparticle drug delivery has been touted as an enabling technology, its potential in treating local skin and systemic diseases has yet to be realised. Most drug delivery particle technologies are based on lipid carriers, i.e. solid lipid nanoparticles and nanoemulsions of around 300 nm in diameter, which are now considered microparticles. Metal nanoparticles are now recognized for seemingly small drug-like characteristics, i.e. antimicrobial activity and skin cancer prevention. We present our unpublished clinical data on nanoparticle penetration and previously published reports that support the hypothesis that nanoparticles N 10 nm in diameter are unlikely to penetrate through the stratum corneum into viable human skin but will accumulate in the hair follicle openings, especially after massage. However, significant uptake does occur after damage and in certain diseased skin. Current chemistry limits both atom by atom construction of complex particulates and delineating their molecular interactions within biological systems. In this review we discuss the skin as a nanoparticle barrier, recent work in the field of nanoparticle drug delivery to the skin, and future directions currently being explored.

We examined whether neuronal proteinase-activated receptor-2 (PAR-2) may be involved in pruritus of human skin. The endogenous PAR-2 agonist tryptase was increased up to fourfold in atopic dermatitis (AD) patients. PAR-2 was markedly enhanced on primary afferent nerve fibers in skin biopsies of AD patients. Intracutaneous injection of endogenous PAR-2 agonists provoked enhanced and prolonged itch when applied intralesionally. Moreover, itch upon mast cell degranulation was abolished by local antihistamines in controls but prevailed in AD patients. Thus, we identified enhanced PAR-2 signaling as a new link between inflammatory and sensory phenomena in AD patients. PAR-2 therefore represents a promising therapeutic target for the treatment of cutaneous neurogenic inflammation and pruritus.

Replacement of the rabbit Draize skin irritation test or the animal photo-irritation test is in course in Europe under the REACH chemical strategy and the Cosmetics Directive. Various in vitro protocols, including 3D skin models, have been assessed. One key difficulty in determining the validity of alternative in vitro methods is that the in vivo animal data is both scarce and often of limited utility for prediction of effects in man. Consequently, we have examined in human 4h patch tests a number of chemicals of EU borderline classification. In addition, in a specific group of cosmetic ingredients we assessed the potential of photoirritation using results obtained in 3D skin models and in human photopatch tests. Several chemicals reported to be irritant in the rabbit were found to be without effect in humans. 3D skin model assays and human patch tests provided concordant results particularly in case of non-irritating and non-phototoxic substances. In our view, skin model tests seem to be a useful tool for the prediction of human skin irritation or phototoxicity hazard, particularly for consideration of initial concentration for confirmatory human patch tests to prove substance and product safety.

ABSTRACT In the United States, chronic wounds affect 6.5 million patients. An estimated excess of US$25 billion is spent annually on treatment of chronic wounds and the burden is rapidly growing due to increasing health care costs, an aging population and a sharp rise in the incidence of diabetes and obesity worldwide. The annual wound care products market is projected to reach $15.3 billion by 2010. Chronic wounds are rarely seen in individuals who are otherwise healthy. In fact, chronic wound patients frequently suffer from &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;highly branded&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; diseases such as diabetes and obesity. This seems to have overshadowed the significance of wounds per se as a major health problem. For example, NIH&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Research Portfolio Online Reporting Tool (RePORT; http://report.nih.gov/), directed at providing access to estimates of funding for various disease conditions does list several rare diseases but does not list wounds. Forty million inpatient surgical procedures were performed in the United States in 2000, followed closely by 31.5 million outpatient surgeries. The need for post-surgical wound care is sharply on the rise. Emergency wound care in an acute setting has major significance not only in a war setting but also in homeland preparedness against natural disasters as well as against terrorism attacks. An additional burden of wound healing is the problem of skin scarring, a $12 billion annual market. The immense economic and social impact of wounds in our society calls for allocation of a higher level of attention and resources to understand biological mechanisms underlying cutaneous wound complications.

Fluorescence confocal scanning laser microscopy (CLSM) using a handheld scanner, was performed to visualize the microscopic architecture of stratum corneum (SC) of the three reconstructed human epidermal (RHE) models: EpiDerm TM (MatTek Corporation, Ashland, MA), EPISKIN R (EPISKIN SNC, Lyon, France) and SkinEthic R (SkinEthic Laboratories, Nice, France). To compare the differences between the SC structure of the RHE models and human SC, experiments were also performed on normal human epidermis in vivo. Sodium fluorescein stained skin cultures and human skin were imaged continuously using the confocal laser microscope Stratum, Optiscan. Fluorescein was excited at 488 nm and the fluorescent emission was detected at > 505 nm. In each experiment, a series of representative images of each visualized layer of the RHE models and human SC was collected. Our early observations confirmed that the reconstructed human skin models closely resemble human SC. After improving the experimental conditions, the method might be used for studying the effects of topically applied compounds e.g. pharmaceuticals and cosmetic to the SC.

Timely and efficient epidermal wound healing is necessary for normal skin barrier function. Cutaneous wound healing involves interactions between dermal fibroblasts and epidermal keratinocytes as well as cell-extracellular matrix interactions (1-4). The current study describes wound healing experiments conducted in a full-thickness in vitro human skin model (EpiDerm-FT). This model exhibits stratified epidermal components and a fully developed basement membrane and resembles in vivo skin in regard to morphology and barrier function. Small epidermal-only wounds (3mm biopsy punch) or full-thickness wounds (cauterizer burns) were induced in the epithelial model and cultures were processed for histological evaluation at various time points to observe the healing process under various conditions. Changes in gene expression during wound healing were also monitored by qPCR.

Topical corticosteroids are used extensively to treat inflammatory skin diseases. Long-term use, however, may be associated with adverse effects such as skin atrophy. New steroids have been developed with the objective of increasing efficacy and reducing the incidence of adverse effects. Mometasone furoate (MMF) is one of these new derivatives. The aim of our study was to compare the effects of MMF and betamethasone-17-valerate (BM-17-valerate) on collagen synthesis in human skin in vivo. Fifteen healthy male volunteers applied MMF, BM-17-valerate and vehicle for 1 week to different areas of abdominal skin. Suction blisters were raised on these areas, and a control site, and procollagen propeptide (PICP, PINP, PIIINP) levels in the suction blister fluid were measured by radioimmunoassay. Skin thickness was measured ultrasonically by Dermascan A at the end of the treatment period. The levels of the three propeptides in suction blister fluid were reduced to similar extent by MMF and BM-17-valerate. The 1-week treatment period had no detectable influence on skin thickness. We conclude that MMF and BM-17-valerate decrease collagen synthesis to the same extent in human skin in vivo.

The refractive index of human skin tissues is an important parameter in characterizing the optical response of the skin. We extended a previously developed method of coherent reflectance curve measurement to determine the in vitro values of the complex refractive indices of epidermal and dermal tissues from fresh human skin samples at eight wavelengths between 325 and 1557 nm. Based on these results, dispersion relations of the real refractive index have been obtained and compared in the same spectral region.

Background and Objective: Dynamics of cryogen spray deposition, water condensation and frost formation is studied in relationship to cooling rate and ef®ciency of cryogen spray cooling (CSC) in combination with laser dermatologic surgery. Study Design/Materials and Methods: A high-speed video camera was used to image the surface of human skin during and after CSC using a commercial device. The in¯uence of ambient humidity on heat extraction dynamics was measured in an atmosphere-controlled chamber using an epoxy block with embedded thermocouples.

1National Centre for Alternative Methods (ZEBET), Berlin, Germany; 2ECVAM, Institute for Health & Consumer Protection, European Commission Joint Research Centre, Ispra, Italy; 3Syngenta, Macclesfield, UK; 4Unilever, Sharnbrook, UK; 5L&#x27;Oréal, Clichy, France; 6ECB, ...

Epithelia establish a microbial barrier against infection through the production of antimicrobial peptides (AMPs). In this study, we investigated whether catestatin (Cst), a peptide derived from the neuroendocrine protein chromogranin A (CHGA), is a functional AMP and is present in the epidermis. We show that Cst is antimicrobial against relevant skin microbes, including Gram-positive and Gram-negative bacteria, yeast, and fungi. The antimicrobial mechanism of Cst was found to be similar to other AMPs, as it was dependent on bacterial charge and growth conditions, and induced membrane disruption. The potential relevance of Cst against skin pathogens was supported by the observation that CHGA was expressed in keratinocytes. In human skin, CHGA was found to be proteolytically processed into the antimicrobial fragment Cst, thus enabling its AMP function. Furthermore, Cst expression in murine skin increased in response to injury and infection, providing potential for increased protection against infection. These data demonstrate that a neuroendocrine peptide has antimicrobial function against a wide assortment of skin pathogens and is upregulated upon injury, thus demonstrating a direct link between the neuroendocrine and cutaneous immune systems.

A continuous rat epidermal cell line (rat epidermal keratinocyte; REK) formed a morphologically well-organized epidermis in the absence of feeder cells when grown for 3 weeks on a collagen gel in culture inserts at an air-liquid interface, and developed a permeability barrier resembling that of human skin. By 2 weeks, an orthokeratinized epidermis evolved with the suprabasal layers exhibiting the differentiation markers keratin 10, involucrin, and filaggrin. Granular cells with keratohyalin granules and lamellar bodies, and corneocytes with cornified envelopes and tightly packed keratin filaments were present. Morphologically, vitamin C supplementation of the culture further enhanced the normal wavy pattern of the stratum corneum, the number of keratohyalin granules present, and the quantity and organization of intercellular lipid lamellae in the interstices of the stratum corneum. The morphological enhancements observed with vitamin C correlated with improved epidermal barrier function, as indicated by reduction of the permeation rates of tritiated corticosterone and mannitol, and transepidermal water loss, with values close to those of human skin. Moreover, filaggrin mRNA was increased by vitamin C, and western blots confirmed higher levels of profilaggrin and filaggrin, suggesting that vitamin C also influences keratinocyte differentiation in aspects other than the synthesis and organization of barrier lipids. The unique REK cell line in organotypic culture thus provides an easily maintained and reproducible model for studies on epidermal differentiation and transepidermal permeation.

Oxidative stress is defined as an imbalance between pro-oxidants and antioxidants in favor of pro-oxidants. Photon emission (also called chemiluminescence) has been widely used to study oxidative stress in biological systems in vitro. In vivo chemiluminescence has been proposed as a non-invasive method to assess oxidative stress in the skin. UVA (320-400 nm part of the ultraviolet radiation) exposure is generally accepted as a source of oxidative stress in the skin. In this study, UVA-induced oxidative stress was studied by using an in vivo chemiluminescence detection method. First, the dose response and the fluence rate response of the UVA-induced oxidative stress in human skin were investigated by examining the decay kinetics of the chemiluminescence signal following UVA exposure. A kinetic model was proposed to help differentiate these two responses. We found that the initial burst of the chemiluminescence signal depended on the UVA fluence rate, whereas the decay of the signal following exposure can be related to the UVA dose involved. Second, a significant reduction of UVA-induced chemiluminescence signal was observed after tape-stripping, indicating that stratum corneum is a major source of UVA-induced oxidative stress in the skin. Furthermore, the oxygen dependence of UVA-induced chemiluminescence signal was also confirmed by application of a pressure cuff, implying that some of the oxidative stress occurs in the deeper layers of the skin. Finally, topical application of vitamin C before exposure significantly reduced the UVA-induced chemiluminescence signal. We thus conclude that chemiluminescence is an effective method to assess the oxidative stress induced by UVA in human skin in vivo.

The term orthodisease has recently been introduced to define human disorders in which the pathogenic gene has orthologs in model organism genomes. Here, we describe Hailey-Hailey disease (HHD), a blistering skin disorder caused by haploinsufficiency of ATP2C1 as an orthodisease from a Saccharomyces cerevisiae perspective. ATP2C1 encodes the human secretory pathway Ca(2+)/Mn(2+) ATPase hSPCA1 and is orthologous to the PMR1 gene in S. cerevisiae. hSPCA1 fully complements PMR1 deficiency in yeast and pmr1DeltaS. cerevisiae has proved to be a valuable tool to screen ATP2C1 mutations and address potential pathogenic/pharmacologic mechanisms in HHD. Consequently, this human skin disorder is an ideal example of an orthodisease.

-ECVAM sponsored a formal validation study on three in vitro tests for skin irritation, of which two employ reconstituted human epidermis models (EPISKIN™, EpiDerm™), and one, the skin integrity function test (SIFT), employs ex vivo mouse skin. The goal of the study was to assess whether the in vitro tests would correctly predict in vivo classifications according to the EU classification scheme, "R38" and "no label" (i.e. non-irritant). 58 chemicals (25 irritants and 33 non-irritants) were tested, having been selected to give broad coverage of physico-chemical properties, and an adequate distribution of irritancy scores derived from in vivo rabbit skin irritation tests. In Phase 1, 20 of these chemicals (9 irritants and 11 nonirritants) were tested with coded identities by a single lead laboratory for each of the methods, to confirm the suitability of the protocol improvements introduced after a prevalidation phase. When cell viability (evaluated by the MTT reduction test) was used as the endpoint, the predictive ability of both EpiDerm and EPISKIN was considered sufficient to justify their progression to Phase 2, while the predictive ability of the SIFT was judged to be inadequate. Since both the reconstituted skin models provided false predictions around the in vivo classification border (a rabbit Draize test score of 2), the release of a cytokine, interleukin-1α (IL-1α), was also determined. In Phase 2, each human skin model was tested in three laboratories, with 58 chemicals. The main endpoint measured for both EpiDerm and EPISKIN was cell viability. In samples from chemicals which gave MTT assay results above the threshold of 50% viability, IL-1α release was also measured, to determine whether the additional endpoint would improve the predictive ability of the tests. For EPISKIN, the sensitivity was 75% and the specificity was 81% (MTT assay only); with the combination of the MTT and IL-1α assays, the sensitivity increased to 91%, with a specificity of 79%. For EpiDerm, the sensitivity was 57% and the specificity was 85% (MTT assay only), while the predictive capacity of EpiDerm was not improved by the measurement of IL-1α release. Following independent peer review, in April 2007 the ECVAM Scientific Advisory Committee endorsed the scientific validity of the EPISKIN test as a replacement for the rabbit skin irritation method, and of the EpiDerm method for identifying skin irritants as part of a tiered testing strategy. This new alternative approach will probably be the first use of in vitro toxicity testing to replace the Draize rabbit skin irritation test in Europe and internationally, since, in the very near future, new EU and OECD Test Guidelines will be proposed for regulatory acceptance.

The field of tissue engineering has opened several avenues in biomedical sciences, through ongoing progress. Skin substitutes are currently optimised for clinical as well as fundamental applications. The paper reviews the development of collagenpopulated hydrated gels for their eventual use as a therapeutic option for the treatment of burn patients or chronic wounds: tools for pharmacological and toxicological studies, and cutaneous models for in vitro studies. These skin substitutes are produced by culturing keratinocytes on a matured dermal equivalent composed of fibroblasts included in a collagen gel. New

One of the recognized side effects of antineoplastic anthracyclines is poor wound healing, resulting from an impairment of collagen biosynthesis. The most affected tissue is skin. The mechanism underlying the tissue specificity of the side effects of anthracyclines has not been established. In view of the fact that a number of pharmacologic agents are known to form complexes with melanin and melanins are abundant constituents of the skin, we determined whether daunorubicin interacts with melanin and how this process affects collagen biosynthesis in cultured human skin fibroblasts. Results indicated that daunorubicin forms complexes with melanin. Scatchard analysis showed that the binding of daunorubicin to melanin was heterogeneous, suggesting the presence of two classes of independent binding sites with K s 1.83 = 10 5 M y1 and K s 5.52 = 10 3 M y1 . The number of strong binding sites was calculated as n s 0.158 mmolrmg potential mechanism for the organ specificity of daunorubicin-induced poor wound healing in patients administered this drug. q 2001 Published by Elsevier Science B.V.

Dust engenders a fear of the unseen, an anxiety and horror at the dissolution of matter to a minute scale; it is amorphous, all pervading, and knows no boundaries. Through the inevitable progress of time the body is transformed and reduced to
dust as the outer layers are shed as dander. In its smallest form the body is grotesque and undelineated. Our dead return to dust but so too do the living. The skins and cells of our moving, breathing bodies disperse into the world, mingling
with foreign matter and waste as we pass through space. Dust forms stagnant veils coating objects of disuse, gathering in corners and floating above our beds. It is an
unsettling and permanent presence, marginal and transitional, without site or bounds.

This paper explores bodies that are decentralised and in a state of dusty disintegration. It addresses the horror of the body in a state of dissipation by asking: where and when does the body begin? Where may it end? And how might the body's transgressed boundaries offer up possibilities for designing wearable artefacts?

The different ultraviolet (UV) wavelength components, UVA (320-400 nm), UVB (280-320 nm), and UVC (200-280 nm), have distinct mutagenic properties. A hallmark of UVC and UVB mutagenesis is the high frequency of transition mutations at dipyrimidine sequences containing cytosine. In human skin cancers, about 35% of all mutations in the p53 gene are transitions at dipyrimidines within the sequence 5&#39;-TCG and 5&#39;-CCG, and these are localized at several mutational hotspots. Since 5&#39;-CG sequences are methylated along the p53 coding sequence in human cells, these mutations may be derived from sunlight-induced pyrimidine dimers forming at sequences that contain 5-methylcytosine. Cyclobutane pyrimidine dimers (CPDs) form preferentially at dipyrimidines containing 5-methylcytosine when cells are irradiated with UVB or sunlight. In order to define the contribution of 5-methylcytosine to sunlight-induced mutations, the lacI and cII transgenes in mouse fibroblasts were used as mutatio...

Simplified skin barrier models are necessary to get a first hand understanding of the very complex morphology and physical properties of the human skin barrier. In addition, it is of great importance to construct relevant models that will allow for rational testing of barrier perturbing/occlusive effects of a large variety of substances. The primary objective of this work was to study the effect of lipid morphology on water permeation through various lipid mixtures (i.e., partly neutralised free fatty acids, as well as a skin lipid model mixture). In addition, the effects of incorporating Azone((R)) (1-dodecyl-azacycloheptan-2-one) into the skin lipid model mixture was studied. Small- and wide-angle X-ray diffraction was used for structure determinations. It is concluded that: (a) the water flux through a crystalline fatty acid-sodium soap-water mixture (s) is statistically significantly higher than the water flux through the corresponding lamellar (L(alpha)) and reversed hexagonal (H(II)) liquid crystalline phases, which do not differ between themselves; (b) the water flux through mixtures of L(alpha)/s decreases statistically significantly with increasing relative amounts of lamellar (L(alpha)) liquid crystalline phase; (c) the addition of Azone((R)) to a skin lipid model system induces a reduction in water flux. However, further studies are needed to more closely characterise the structural basis for the occlusive effects of Azone((R)) on water flux.

BACKGROUND. Nonablative methods may produce collagen synthesis in sun-damaged skin. OBJECTIVE. To study the effects of intense pulsed light (IPL) and 1,064 nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser: a histologic and immunohistochemical analysis of sundamaged skin. MATERIALS AND METHODS. Nine subjects participated. Five subjects received five-monthly treatments with IPL (560 nm cutoff filter, 8 ϫ 35 mm spot size, pulse duration 2.4/4.2 milliseconds, pulse delay 15 milliseconds, fluence 28-35 J/cm 2 ). Four subjects received treatment with a 1,064 nm Nd:YAG laser (130 J/cm 2 , triple pulse, 7.0/7.0/7.0-millisecond pulse duration, 75-millisecond delay). Routine histology and immunohistochemistry on 2 mm punch biopsies were taken before treatment and then at 3

Antimicrobial peptides of the β-defensin family are expressed in all human epithelial tissues tested to date and have recently been the subject of vigorous investigation. Their localization and characteristics support the hypothesis that these peptides play a role in mucosal and skin defense. The lipophilic yeast Malassezia furfur is a saprophyte found in normal human cutaneous flora. Malassezia furfur is not only a saprophyte, but is also associated with several diseases such as Malassezia folliculitis, seborrheic dermatitis and some forms of atopic dermatitis, psoriasis and confluent and reticulate papillomatosis. Little is known about the mechanism by which M. furfur overcomes the natural barrier of the skin. To further define the role of the β-defensins in the innate human skin immune response, we analyzed the mRNA expression of two human β-defensins HBD-1 and HBD-2 in human keratinocytes treated with M. furfur. In addition, we looked into how M. furfur of TGF-β1 and IL-10, cytokines that interfere with the development of protective cell immunity, regulate their expression. Finally, we examined the signal transduction mechanisms involved during M. furfur uptake. Cultured human keratinocytes were treated with M. furfur. The mRNA and protein expression were analyzed, respectively, by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting. Our data demonstrate that M. furfur does not modify HBD-1 expression, whereas it up-regulates, via protein kinase C (PKC), the expression of HBD-2, TGFβ-1 and IL-10 48 h after treatment. Our results suggest that β-defensins are integral components of innate host defenses. They play an essential part in the resistance of the human skin surfaces against M. furfur uptake and other microbial invasion.

Psoriasis, a common cutaneous disease of unknown etiology, may be triggered by infections, including those due to fungi. Since the fungal community of human skin is poorly characterized, we aimed to analyze the mycological microbiota in healthy skin and psoriatic lesions. Twenty-five skin samples from five healthy subjects (flexor forearm) and three patients with psoriasis were analyzed using broad-range 18S ribosomal DNA (rDNA) and 5.8S rDNA/internal transcribed spacer 2 (ITS2) Malassezia-specific PCR primers. Broadrange PCR analysis indicated that most organisms resembled Malassezia. Malassezia-specific 5.8S/ITS2 analysis of 1,374 clones identified five species and four unknown phylotypes, potentially representing new species. The species distribution appears largely host specific and conserved in different sites of healthy skin. In three subjects, the Malassezia microbiota composition appeared relatively stable over time. Samples of Malassezia microbiota from healthy skin and psoriatic lesions were similar in one patient but substantially different in two others. These data indicate the predominance of Malassezia organisms in healthy human skin, host-specific variation, stability over time, and as yet, no consistent patterns differentiating psoriatic skin from healthy skin.

There is an urgent need to validate in vitro human skin models for use in safety testing. An important component of validation is characterizing the metabolizing capacity of these models. We report comparison of the expression of 139 genes encoding xenobiotic metabolizing enzymes in the EpiDerm™ model and human skin. In microarray analysis, the expression of 87% of the genes was consistent between the EpiDerm™ model and human skin indicating the presence of similar metabolic pathways suggesting commonality in function. Analysis of EpiDerm™ models constructed from four donors showed highly comparable expression of xenobiotic metabolizing genes demonstrating reproducibility of the model. Overall, the expression of Phase II enzymes appeared to be more pronounced in human skin and the Epi-Derm™ model than that of Phase I enzymes, consistent with the role of skin in detoxification of xenobiotics. Though the basal expression of CYPs in particular was low in EpiDerm™, significant induction of CYP1A1/1B1 activity was observed following treatment with 3-methylcholanthrene. These results indicate that the xenobiotic metabolizing capacity of the EpiDerm™ model appears to be representative of human skin. Models such as EpiDerm™ provide a valuable in vitro approach for evaluation of metabolism and toxicity of cutaneous exposures to xenobiotics.

Multiphoton tomography was used to examine xenobiotic transport in vivo. We used the photochemical properties of zinc oxide and fluorescein and multiphoton tomography to study their transport in the skin and in the rat liver in vivo. Zinc oxide nanoparticles were visualised in human skin using the photoluminescence properties of zinc oxide and either a selective emission wavelength band pass filter or a filter with fluorescence lifetime imaging (FLIM). Zinc oxide nanoparticles (30 nm) did not penetrate into human skin in vitro and in vivo and this was validated by scanning electron microscopy with X-ray photoelectron spectroscopy. Fluorescein was measured in the liver using FLIM. Fluorescein is rapidly extracted from the blood into the liver cells and then transported into the bile. It is suggested that multiphoton tomography may be of particular use in defining in vivo 4D (in both space and time) pharmacokinetics.

Studies in terahertz (THz) imaging have revealed a significant difference between skin cancer (basal cell carcinoma) and healthy tissue. Since water has strong absorptions at THz frequencies and tumours tend to have different water content from normal tissue, a likely contrast mechanism is variation in water content. Thus, we have previously devised a finite difference timedomain (FDTD) model which is able to closely simulate the interaction of THz radiation with water. In this work we investigate the interaction of THz radiation with normal human skin on the forearm and palm of the hand in vivo. We conduct the first ever systematic in vivo study of the response of THz radiation to normal skin. We take in vivo reflection measurements of normal skin on the forearm and palm of the hand of 20 volunteers. We compare individual examples of THz responses with the mean response for the areas of skin under investigation. Using the in vivo data, we demonstrate that the FDTD model can be applied to biological tissue. In particular, we successfully simulate the interaction of THz radiation with the volar forearm. Understanding the interaction of THz radiation with normal skin will form a step towards developing improved imaging algorithms for diagnostic detection of skin cancer and other tissue disorders using THz radiation.

Human skin allografts are used in the treatment of severe burns and their preservation is therefore critical for optimal clinical benefit. Current preservation methods, such as 4 degrees C storage or cryopreservation, cannot prevent the decrease of tissue viability. The aim of this study was to assess viability and function of skin allografts in a new skin organ culture model, allowing conservation parameters as close as possible to physiological conditions: 32 degrees C, air-liquid interface and physiological skin tension. Twelve skin samples, harvested from 6 living surgical donors, were conserved 35 days in two conditions: conservation at 4 degrees C and organ culture. Viability and function of skin samples were investigated at Day 0, 7, 14, 21, 28 and 35 using cell culture methods (trypan blue exclusion, Colony Forming Efficiency and Growth Rate), histopathological and histoenzymological studies (Ki67 immunostaining). In the two conditions, fibroblast and keratinocyte viability ...