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At least 217 records · Page 12Linked to original sources

Measurement and perception of skin colour in a skin cancer survey.

A population-based prevalence survey of skin cancer was conducted in Nambour, Queensland, in 1986. The skin colour of 807 participants was assessed in three ways: quantitatively, graded by a dermatologist, and self-reported. Quantitation of skin pigmentation was obtained by measuring the reflectance of light of wavelength 650 nm, at six sites. Females showed higher mean reflectance (paler skin) than males at all sites with the greatest difference on the lateral forearms. Prevalent skin cancer in males, and solar keratoses in both sexes were correlated with inherently pale skin colour on an unexposed site, and the presence of keratoses was correlated with darkly-pigmented backs of the hands (P less than 0.001). Both dermatologists' and participants' grading of skin colour were moderately correlated with measured skin colour. For dermatologists, correlation was highest with reflectance from the medial upper arms (r = 0.35, right arm; 0.30, left) in males, and the lateral forearms (r = 0.34, right; 0.38, left) in females. Correlations between reflectance values and self-reported innate skin colour were highest for the upper arms (r = 0.26, right; 0.24, left) in males, and for forearms (r = 0.42, right and left) in females. Prevalence of actinic lesions was more highly correlated with subjectively assessed skin colour than with quantitative skin pigmentation.

Adult↗

Biology of estrogens in skin: implications for skin aging.

Estrogens have a profound influence on skin. The relative hypoestrogenism that accompanies menopause exacerbates the deleterious effects of both intrinsic and environmental aging. Estrogens clearly have a key role in skin aging homeostasis as evidenced by the accelerated decline in skin appearance seen in the perimenopausal years. Estrogens improve skin in many ways. Among these, they increase collagen content and skin thickness and improve skin moisture. However, despite the knowledge that estrogens have such important effects on skin, the cellular and subcellular sites and mechanisms of estrogen action are still poorly understood. Estrogen receptors (ERs) have been detected in skin, and recent studies suggest that estrogens exert their effect in skin through the same molecular pathways used in other non-reproductive tissues. Although systemic hormone replacement therapy (HRT) has been used for many years, recent trials have reported a significant increased risk of breast cancer and other pathologies with this treatment. This has led to reconsider the risks and benefits of HRT. For this reason, systemic HRT cannot be recommended today to treat skin aging. Currently, intensive research is conducted to develop new drugs called selective ER modulators (SERMs). These drugs exert mixed estrogenic and antiestrogenic effects depending on the tissue and cell type. One might expect in the future such a drug targeting specifically the skin without systemic side effects.

Androgens↗

A novel ATX-S10(Na) photodynamic therapy for human skin tumors and benign hyperproliferative skin.

BACKGROUND/PURPOSE: Photodynamic therapy (PDT) is a promising treatment for various skin tumors and other skin diseases. We investigated the potential therapeutic effects of PDT using ATX-S10(Na) ointment and a diode laser in mouse skin models of experimental skin tumors as well as transplanted human samples of superficial skin tumors and lesional psoriatic skin. METHODS: ATX-S10(Na) ointment (1% w/v) was introduced into tape-stripped mouse skin, transplanted squamous cell carcinoma (SCC) samples and human skin diseases after topical application, then PDT was performed. RESULTS: ATX-S10(Na) ointment (1% w/v) was introduced effectively into tape-stripped mouse skin and transplanted SCC samples after topical application, but was not detected after 48 h, as assessed by fluorescence microscopy. PDT, using 1% ATX-S10(Na) ointment and diode laser (50 J/cm(2)), was found to decrease epidermal thickness in 12-0-tetradecanoylphorbol-13-acetate (TPA)-treated mouse skin by 6 days. PDT with 1% ATX-S10(Na) ointment and diode laser (150 J/cm(2)) was also effective for transplanted SCC, and tumors were eliminated by 6 weeks. PDT against Bowen disease, basal-cell carcinoma, and psoriasis xenografts onto SCID mice also showed marked suppression of tumor growth and cell proliferation, respectively. CONCLUSION: Our results indicate that ATX-S10(Na)-PDT is an effective treatment for various skin tumors and psoriasis in experimental mouse models.

Animals↗

Fate of chemicals in skin after dermal application: does the in vitro skin reservoir affect the estimate of systemic absorption?

Recent international guidelines for the conduct of in vitro skin absorption studies put forward different approaches for addressing the status of chemicals remaining in the stratum corneum and epidermis/dermis at the end of a study. The present study investigated the fate of three chemicals [dihydroxyacetone (DHA), 7-(2H-naphtho[1,2-d]triazol-2-yl)-3-phenylcoumarin (7NTPC), and disperse blue 1 (DB1)] in an in vitro absorption study. In these studies, human and fuzzy rat skin penetration and absorption were determined over 24 or 72 h in flow-through diffusion cells. Skin penetration of these chemicals resulted in relatively low receptor fluid levels but high skin levels. For DHA, penetration studies found approximately 22% of the applied dose remaining in the skin (in both the stratum corneum and viable tissue) as a reservoir after 24 h. Little of the DHA that penetrates into skin is actually available to become systemically absorbed. 7NTPC remaining in the skin after 24 h was approximately 14.7% of the applied dose absorbed. Confocal laser cytometry studies with 7NTPC showed that it is present across skin in mainly the epidermis and dermis with intense fluorescence around hair. For DB1, penetration studies found approximately 10% (ethanol vehicle) and 3% (formulation vehicle) of the applied dose localized in mainly the stratum corneum after 24 h. An extended absorption study (72 h) revealed that little additional DB1 was absorbed into the receptor fluid. Skin levels should not be considered as absorbed material for DHA or DB1, while 7NTPC requires further investigation. These studies illustrate the importance of determining the fate of chemicals remaining in skin, which could significantly affect the estimates of systemically available material to be used in exposure estimates. We recommend that a more conclusive means to determine the fate of skin levels is to perform an extended study as conducted for DB1.

Administration, Cutaneous↗

Attitudes and intentions in relation to skin checks for early signs of skin cancer.

BACKGROUND: Screening for melanoma by whole-body clinical skin examination or skin self-examination may improve early diagnosis of melanoma. As part of the first phase of a community-based randomised controlled trial of screening for melanoma, this study examined the prevalence of skin screening intentions and associated factors in a population at high risk for skin cancer. METHODS: A telephone survey stratified by gender reached 3,110 participants > or = 30 years representative for the population. RESULTS: Overall, 45% intended to have a clinical skin check, and 72% intended to examine their own skin within the next 12 months. In multivariate analysis, a history of a clinical skin examination was most strongly related to intention to screen. Concern about skin cancer or a personal history of skin cancer and high susceptibility towards skin cancer were further important determinants of screening intention. Men were less likely than women to intend participation. CONCLUSIONS: Given that skin screening is not recommended by health authorities in absence of scientific evidence of benefit, the intention to participate in screening for melanoma in this Australian sample was high. Except for the lower intention among men, screening intention appears to be highest in those at highest risk of melanoma.

Adult↗

Allergen-induced histamine release in intact human skin in vivo assessed by skin microdialysis technique: characterization of factors influencing histamine releasability.

BACKGROUND: The purposes of the study were to characterize allergen-induced histamine release in intact human skin in vivo by using a novel microdialysis technique and to study covariates influencing histamine releasability. METHODS: Hollow microdialysis fibers were inserted into the upper dermis in 15 timothy-sensitivity subjects. Up to 12 fibers were inserted in each subject. Each fiber was perfused with Krebs-Ringer's solution at a rate of 3.0 microliters/min. Three to four serial dilutions of allergen were applied to the skin by intracutaneous injections or skin prick test above individual fibers. Samples were collected in two 2-minute fractions before skin challenge and in 10 consecutive samples for 20 minutes after skin challenge. Histamine was assayed spectrofluorometrically. RESULTS: A significant dose-response relationship for histamine release was demonstrated with intracutaneous tests and skin prick tests. The time to reach peak histamine release after an intracutaneous test was 4 to 8 minutes, compared with 12 to 14 minutes for a skin prick test. Histamine release correlated significantly with wheal size. Intrasubject coefficient of variation on histamine release was about 20%. A substantial intersubject variation in histamine releasability was observed. Seventy to seventy-five percent of the variation could be accounted for by a combination of gender, total and allergen-specific IgE, and an in vitro basophil histamine release test. CONCLUSIONS: Using a skin microdialysis technique, we have described in detail histamine release in intact human skin by allergen. The microdialysis method proved to be a reproducible technique for monitoring histamine release in allergic skin reactions and for studying histamine releasability of skin mast cells in vivo.

Adult↗

Melanoma invasion in reconstructed human skin is influenced by skin cells--investigation of the role of proteolytic enzymes.

Melanoma invasion is a complex multi stage process involving changes to the cell/extracellular matrix (ECM) and cell/cell interactions. We have previously shown using an in vitro model of reconstructed human skin (consisting of human dermis with a basement membrane [BM] and populated with human skin cells) that some melanoma cells (HBL cell line) invade more actively in the presence of adjacent normal skin cells. The aim of the present study was to further investigate the relationship between melanoma cells, skin cells and ECM proteins during melanoma cell invasion through reconstructed skin, extending this to a study of three melanoma cell lines. We also examined whether such cell/cell induced invasion is due to increased expression and activation of matrix-metalloproteinase-2 (MMP-2) and MMP-9, or due to increases in general protease activity for keratinocytes, fibroblasts or melanoma lines. Addition of skin cells dramatically altered the invasive behaviour of the three metastatic melanoma cell lines (HBL, C8161 and A375SM) used; they increased the invasive ability of HBLs which were unable to invade on their own; they potentiated the invasion of C8161 cells which were invasive in their own right, but reduced the invasion of A375-SM cells which were aggressive invaders in the absence of skin cells. Latent forms of MMP-2, and MMP-9, were clearly expressed by the normal skin cells whereas all three melanoma lines weakly expressed these proteases. Fibroblast and keratinocyte MMPs were activated specifically by culture on type I collagen and on dermis which retained an intact basement membrane. These findings demonstrate that while there is an active communication between melanoma cells and adjacent skin cells, the invasive process is dictated by the melanoma cells and not the skin cells. However, activation of skin cell derived MMPs may play an important role in facilitating invasion by particular melanoma phenotypes.

Cell Communication↗

Similar UV responses are seen in a skin organ culture as in human skin in vivo.

Ultraviolet radiation (UVR) plays an important role in the development of non-melanoma skin cancer. Most tumors develop in chronically sun-exposed skin, most often in cosmetically sensitive locations, where in vivo experiments may be difficult to perform. In this study, we describe a skin organ culture model with preserved normal morphology and intact response to UVR. Skin explants from chronically sun-exposed and non-sun-exposed skin were irradiated with artificial UVA+UVB with and without topical sunscreen. UV-induced DNA damage, epidermal p53 response and repair kinetics were analyzed using immunohistochemistry. Four hours after UV-irradiation epidermal keratinocytes showed a strong immunoreactivity for thymine-dimers. Gradual repair during an incubation time resulted in few residual thymine-dimers after 48 h. Repair appeared to be more efficient in chronically sun-exposed skin compared with non-sun-exposed skin. There was also an accumulation of p53 protein in epidermal keratinocytes, peaking at 4-24 h after irradiation. Large interindividual differences with respect to formation and repair of thymine-dimers as well as induction and duration of the p53 response were observed. Skin explants treated with topical sunscreen prior to UV-irradiation showed a clear reduction of thymine-dimers and p53 expression. The epidermal UV-responses and repair kinetics in organ-cultured skin were similar to what was found in vivo. Our data suggest that organ-cultured skin provides a valuable tool for studies of UV-induced epidermal responses in chronically sun-exposed skin.

Adult↗

Skin sensitization: modeling based on skin metabolism simulation and formation of protein conjugates.

A quantitative structure-activity relationship (QSAR) system for estimating skin sensitization potency has been developed that incorporates skin metabolism and considers the potential of parent chemicals and/or their activated metabolites to react with skin proteins. A training set of diverse chemicals was compiled and their skin sensitization potency assigned to one of three classes. These three classes were, significant, weak, or nonsensitizing. Because skin sensitization potential depends upon the ability of chemicals to react with skin proteins either directly or after appropriate metabolism, a metabolic simulator was constructed to mimic the enzyme activation of chemicals in the skin. This simulator contains 203 hierarchically ordered spontaneous and enzyme controlled reactions. Phase I and phase II metabolism were simulated by using 102 and 9 principal transformations, respectively. The covalent interactions of chemicals and their metabolites with skin proteins were described by 83 reactions that fall within 39 alerting groups. The SAR/QSAR system developed was able to correctly classify about 80% of the chemicals with significant sensitizing effect and 72% of nonsensitizing chemicals. For some alerting groups, three-dimensional (3D)-QSARs were developed to describe the multiplicity of physicochemical, steric, and electronic parameters. These 3D-QSARs, so-called pattern recognition-type models, were applied each time a latent alerting group was identified in a parent chemical or its generated metabolite(s). The concept of the mutual influence amongst atoms in a molecule was used to define the structural domain of the skin sensitization model. The utility of the structural model domain and the predictability of the model were evaluated using sensitization potency data for 96 chemicals not used in the model building. The TIssue MEtabolism Simulator (TIMES) software was used to integrate a skin metabolism simulator and 3D-QSARs to evaluate the reactivity of chemicals thus predicting their likely skin sensitization potency.

Animals↗

Pig ear skin as an in-vitro model for human skin permeability.

Pig skin has been shown to have similar histological and physiological properties to human skin and has been suggested as a good model for human skin permeability. In this series of experiments, the in-vitro permeability of pig ear skin was compared with human (abdominal) skin and rat (dorsal) skin using both hydrophilic (water, mannitol, paraquat) and lipophilic (aldrin, carbaryl, fluazifop-butyl) penetrants. Pig skin was found to have a closer permeability character than rat skin to human skin, particularly for lipophilic penetrants. Electrical conductivity measurements across pig skin membranes showed that skin conductivity could be a useful method for assessing the integrity of membranes, particularly when used in conjunction with water permeability assessments.

Animals↗

Skin to skin care:heat balance.

Skin to skin care has been practised in primitive and high technology cultures for body temperature preservation in neonates. Regional skin temperature and heat flow was measured in moderately hypothermic term neonates to quantitate the heat transfer occurring during one hour of skin to skin care. Nine healthy newborns with a mean rectal temperature of 36.3 degrees C were placed skin to skin on their mothers' chests. The mean (SD) rectal temperature increased by 0.7 (0.4) degrees C to 37.0 degrees C. The heat loss was high (70 Wm-2) from the unprotected skin of the head to the surrounding air. Minute heat losses occurred from covered areas; and heat was initially gained from areas in contact with the mother's skin. The total dry heat loss during skin to skin care corresponded to heat loss during incubator care at 32-32.5 degrees C. The reduced heat loss, and to a minor extent, the initial heat flux from the mothers allowed heat to be conserved, leading to rewarming.

Body Temperature Regulation↗

Involved and uninvolved skin from psoriatic subjects: are they equally diseased? Assessment by skin transplanted to congenitally athymic (nude) mice.

A highly significant, but unanswered, question in the pathogenesis of psoriasis relates to how normal appearing and diseased skin can coexist, undergo spontaneous flares and remissions, and yet appear to be genetically acquired. A plausible explanation for these disparate observations is that there is a basic defect in epidermal proliferation of skin of subjects with psoriasis and that disease expression is governed by other host factors. To address this question, we compared epidermal proliferation of skin involved and uninvolved with psoriasis with normal skin before and after transplantation to congenitally athymic (nude) mice, a biologic milieu free of humoral factors unique to the donor host. Results demonstrated that (a) before transplant, synthesis of DNA by the epidermal cells from skin uninvolved and involved with psoriasis is significantly higher than normal, 1.6 and 3.6 times, respectively; (b) 6 wk after transplantation, synthesis of DNA by epidermal cells is unchanged for normal skin, increased for uninvolved skin, and decreased for involved skin. These increases and decreases are of such a magnitude that at 6 wk the number of epidermal cells synthesizing DNA per 1,000 basal cells is identical, and is 2.2 times that of normal skin. When removed from the milieu of the afflicted host, skin involved and uninvolved with psoriasis appear equally "diseased." These data support the notion that there is aberrant epidermal proliferation in skin of patients with psoriasis and that host factors appear to play a role both in the expression and nonexpression of this disease.

Adult↗

Utility of a three-dimensional cultured human skin model as a tool to evaluate the simultaneous diffusion and metabolism of ethyl nicotinate in skin.

The simultaneous diffusion and metabolism of ethyl nicotinate (EN) in a cultured human skin model, Living Skin Equivalent-high, was evaluated by the in vitro skin permeation and metabolism experiments, and esterase distribution was also determined. Theoretical calculations using Fick's 2nd Law of Diffusion with Michaelis-Menten kinetics were performed to obtain the permeation and metabolic parameters together with information on enzyme distribution. The obtained data was compared with the corresponding results in excised hairless rat skin. The partition coefficient of EN from the vehicle to the skin was of the same order of magnitude for the cultured human skin and hairless rat skin, but the diffusion and metabolic parameters were different. Esterase concentration in the epidermal membrane was greater than in the dermis of cultured skin, which was similar to hairless rat skin. Taking into account the similarities and differences between the membranes, the cultured human skin model can be utilized as a model membrane to rapidly predict simultaneous diffusion and metabolism of the prodrug through human skin.

Algorithms↗

Pattern of use of skin care products in children with and without eczematous skin lesions.

OBJECTIVE: To compare the pattern of use of skin care products between children with eczematous skin lesions and those without. DESIGN: Case control study. SETTING: Two well baby clinics at the Kenyatta National Hospital and the Mbagathi District Hospital in Nairobi. SUBJECTS: Eighty nine infants with eczematous skin lesions and 89 age and sex matched controls without skin lesions. MAIN OUTCOME MEASURES: Presence and severity of skin lesions related to the type of skin care products used by the child. RESULTS: Exposure to various products was not significantly different between infants with skin lesions and those without. However, more mothers whose children had a skin rash had made a change in the type of soap and or skin cream used for their child (p<0.0001). The principal reason for changing products was skin rash in the baby and most mothers made changes away from scented baby soap products. CONCLUSION: The study found no significant difference between the cases and controls regarding the type of skin care products used.

Age of Onset↗

[Irradiated porcine skin impregnated with fluorine and silver covered by autogenous granule skin graft for treating severe burn injury].

OBJECTIVE: To study the feasibility of using irradiated porcine skin impregnated with fluorine and silver covered by autogenous skin granule graft in the treatment of severe burn injury. METHODS: Autogenous split-thick skin grafts were cut into small pieces (<1 mm3), which were transferred onto the sheet of porcine skin mounted with a layer of Xinnaxing ointment (2 mm in thickness). After eschar removal, the burn wound was covered with the prepared porcine skin, sutured and fixed with small holes at the lower site for drainage. The growth of autogenous granule skin was then observed and the criteria for therapeutic effect evaluation drafted. RESULTS: The layer of Xinnaxing ointment on the the porcine skin improved the adhesion of the autogenous small skin grafts, therefore full use could be made of the donor skin source. In the 15 patients receiving this treatment, the graft-covered area was (12.3+/-3.5) % that of the wound, with the donor-recipient area ratio of 1: (11.0+/-2.7) and subsequent healing time of 27.5+/-5.5 d. Primary healing was achieved in 9 cases, and secondary healing in 6, demonstrating similar clinical effect to that of allo-skin grafting. CONCLUSION: The method is easy and economic, which saves autogenous skin source and produces satisfactory clinical effect.

Adult↗

Differences in latency and inducibility of mouse skin melanomas depending on the age and anatomic site of the skin.

To determine whether the occurrence of skin melanoma is influenced by the age or the anatomic source of the skin in melanoma-susceptible transgenic mouse models, skin was grafted from donors of different ages or from different anatomic sites to a standard (lateral trunk) site in adult recipients of the same transgenic strain. In 27 grafts of neonatal body skin, melanomas arose with a significantly shorter latency than in 37 grafts of older body skin. The difference may reflect not only the larger number of extrafollicular melanocytes in a given area of neonatal skin but also their unusually high mitotic activity shortly after birth and the influence of other growing skin cells nearby. Each of these body-skin grafts usually developed a single tumor situated near the graft edge. Because maximal wound healing occurs at the edge of such full-thickness skin grafts, melanocytes near the edge would receive the highest exposure to growth factors and cytokines associated with wound healing. In contrast to these results, grafts of snout skin yielded many melanomas, each originating from melanocytes within a vibrissa follicle rather than at the graft edge. The relatively strong local tumorigenic stimulus may be attributable to intrafollicular growth factors normally involved in whisker growth. The above-described experiments support the conclusion that agents in the immediate skin environment of the melanocyte, in addition to the state of the melanocyte itself, contribute to melanoma formation.

Age Factors↗

Skin response to histamine. Reproducibility study of the dry skin prick test method and of the evaluation of microvascular changes with laser Doppler flowmetry.

The author presents original data obtained when using the dry skin prick test method to introduce histamine into the skin and by non-invasive evaluation of the skin blood flow changes at various sites/times during the development of the weal and flare reaction. The test method (1-second prick test duration and evaluation with laser Doppler flowmetry) generated reproducible responses when repeated in the same group of subjects (n = 10). At predefined fixed skin locations within the histamine-induced flare reaction area increased volumes of skin blood flow were recorded. When similar locations were explored after the control prick test, there were only minimal changes in skin blood flow. Pooled data recorded at four different sites located 1 cm from prick sites showed minimal variation and skin perfusion volumes were greater than basal values. The development of the histamine-dependent weal in its early phase (9th min) was associated with slightly smaller numbers of skin blood perfusion units, compared with recordings made during the 15th min. The control prick tests showed slightly higher levels at 9 min than at 15 min. This inverse relationship might be useful to quantify the histamine-specific changes in skin blood flow. These data also clearly illustrate that it is mandatory to state the precise place of measurement and time after challenge when reporting on instrumental evaluation of the skin response to histamine.

Adult↗

In vitro percutaneous absorption in mouse skin: influence of skin appendages.

Skin appendages are often envisaged as channels that bypass the stratum corneum barrier and are generally thought to facilitate the dermal absorption of topical agents. However, the significance of this transappendageal pathway in percutaneous absorption remains to be assessed experimentally. With the use of a skin organ culture penetration chamber system, the influence of skin appendages on the in vitro permeation of topically applied benzo[a]pyrene and testosterone (5 micrograms/2 cm2) was examined in skin preparations from both haired and hairless mice. Haired mice examined included the C57BL6, C3H, DBA2, Balbc, and Sencar strains and the hairless mice were the HRS and SKH. In all mouse strains examined, the overall permeation of testosterone (greater than 65% of applied dose) 16 hr following in vitro topical application was greater than that of benzo[a]pyrene (less than 10%). No strain differences were observed with respect to the percutaneous permeation of testosterone; however, percutaneous permeation of benzo[a]pyrene in the haired mice (7-10% of applied dose) was higher than that in the hairless mice (2%). In an in-house derived mouse strain which showed three phenotypic variants due to hair densities, the permeability to both compounds was highest in the skin of the haired phenotype (testosterone 67%, benzo[a]pyrene 7%), lowest in the hairless phenotype (35 and 1%, respectively) and intermediate in the fuzzy-haired animal (57 and 3%, respectively). Examination by fluorescence microscopy of cryosections of skin, prepared 1 hr after topical benzo[a]pyrene, showed areas of intense fluorescence deep within the nonfluorescing dermis of skin from the haired phenotype. These fluorescent areas were correlated with follicular ducts and sebaceous glands. In contrast, skin from the hairless phenotype showed no evidence of fluorescence in the dermis and intermediate was the fluorescence observed in the skin from the fuzzy-haired animal. These observations showed that transappendageal penetration could contribute significantly to the overall skin absorption of topical agents. They also suggest that regional distribution of skin appendages could influence the percutaneous fate of topically applied chemicals.

Animals↗