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Sample records for hairless micropig skin

  1. Hairless micropig skin. A novel model for studies of cutaneous biology.

    PubMed Central

    Lavker, R. M.; Dong, G.; Zheng, P. S.; Murphy, G. F.

    1991-01-01

    Reported here is the structural and immunohistochemical similarities between the Yucatan hairless micropig (HMP) skin and that of humans. Hairless micropig skin surface was composed of complex intersecting furrows that created geometric patterns remarkably similar to human skin surface glyphics. The dermal--epidermal interface consisted of undulant downgrowths that interdigitated with dermal papillae. Hairless micropig epidermis contained two morphologically distinct populations of basal keratinocytes (serrated and nonserrated). Similar heterogeneity has been seen only in human epidermis and primate palmar epidermis. Immunohistochemistry revealed that the HMP epidermis is reactive with monoclonal and polyclonal antisera to keratin proteins. Melanocytes reactive with antisera to S-100 protein, as in human skin, also were observed in HMP epidermis. Organization of dermal extracellular matrix, including collagen and elastic fibers, and the organization and reactivity of the microvasculature with antisera to factor VIII, were consistent with human skin. The costicosteroid-induced atrophy and subsequent rebound phenomenon after withdrawal of steroid observed in HMP skin was similar with that observed in humans. It is concluded that HMP skin approximates human skin significantly more precisely than most existing species and is an excellent model for studies of cutaneous physiology and pharmacology. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2000942

  2. The hairless mouse in skin research

    PubMed Central

    Benavides, Fernando; Oberyszyn, Tatiana M.; VanBuskirk, Anne M.; Reeve, Vivienne E.; Kusewitt, Donna F.

    2009-01-01

    Summary The hairless (Hr) gene encodes a transcriptional co-repressor highly expressed in the mammalian skin. In the mouse, several null and hypomorphic Hr alleles have been identified resulting in hairlessness in homozygous animals, characterized by alopecia developing after a single cycle of relatively normal hair growth. Mutations in the human ortholog have also been associated with congenital alopecia. Although a variety of hairless strains have been developed, outbred SKH1 mice are the most widely used in dermatologic research. These unpigmented and immunocompetent mice allow for ready manipulation of the skin, application of topical agents, and exposure to UVR, as well as easy visualization of the cutaneous response. Wound healing, acute photobiologic responses, and skin carcinogenesis have been extensively studied in SKH1 mice and are well characterized. In addition, tumors induced in these mice resemble, both at the morphologic and molecular levels, UVR-induced skin malignancies in man. Two limitations of the SKH1 mouse in dermatologic research are the relatively uncharacterized genetic background and its outbred status, which precludes inter-individual transplantation studies. PMID:18938063

  3. Photodynamic therapy improves the ultraviolet-irradiated hairless mice skin

    NASA Astrophysics Data System (ADS)

    Jorge, Ana Elisa S.; Hamblin, Michael R.; Parizotto, Nivaldo A.; Kurachi, Cristina; Bagnato, Vanderlei S.

    2014-03-01

    Chronic exposure to ultraviolet (UV) sunlight causes premature skin aging. In light of this fact, photodynamic therapy (PDT) is an emerging modality for treating cancer and other skin conditions, however its response on photoaged skin has not been fully illustrated by means of histopathology. For this reason, the aim of this study was analyze whether PDT can play a role on a mouse model of photoaging. Hence, SKH-1 hairless mice were randomly allocated in two groups, UV and UV/PDT. The mice were daily exposed to an UV light source (280-400 nm: peak at 350 nm) for 8 weeks followed by a single PDT session using 20% 5-aminolevulinic acid (ALA) topically. After the proper photosensitizer accumulation within the tissue, a non-coherent red (635 nm) light was performed and, after 14 days, skin samples were excised and processed for light microscopy, and their sections were stained with hematoxylin-eosin (HE) and Masson's Trichrome. As a result, we observed a substantial epidermal thickening and an improvement in dermal collagen density by deposition of new collagen fibers on UV/PDT group. These findings strongly indicate epidermal and dermal restoration, and consequently skin restoration. In conclusion, this study provides suitable evidences that PDT improves the UV-irradiated hairless mice skin, supporting this technique as an efficient treatment for photoaged skin.

  4. In vivo skin penetration of salicylic compounds in hairless rats.

    PubMed

    Simonsen, Lene; Petersen, Mads B; Groth, Lotte

    2002-10-01

    The in vivo skin penetration of four salicylic compounds was investigated using a hairless rat model, which allowed for non-occluded, finite dose application, and free mobility of the rats throughout the test period. The model compounds were applied in equimolal concentrations of 0.4 mmol/g dimethyl isosorbide. At certain times (0.5-24 h) the rats were killed, and the amount of test compound on the skin surface, in the stratum corneum, and in the deeper viable skin layers was determined. Significant different skin concentrations were found with the following ranking: [(14)C]diethylamine salicylate>[(14)C]salicylic acid>[(14)C]salicylamide>[(14)C]butyl salicylate. In addition, the in vivo percutaneous rate of absorption was in the following order: [(14)C]butyl salicylate>[(14)C]salicylic acid> or =[(14)C]salicylamide>[(14)C]diethylamine salicylate. [(14)C]Butyl salicylate was rapidly absorbed and completely depleted from the surface 3 h post application. In comparison with [(14)C]salicylic acid, the ionic [(14)C]diethylamine salicylate had larger surface depots and penetrated the skin at a lower rate. The relatively hydrophilic [(14)C]salicylamide also had larger surface depots but much lower skin levels. For comparison, the in vitro permeation of the formulations was studied through freshly excised hairless rat skin using Franz diffusions cells, and an agreement between the techniques was found.

  5. Diffusion of (2-/sup 14/C)diazepam across hairless mouse skin and human skin

    SciTech Connect

    Koch, R.L.; Palicharla, P.; Groves, M.J.

    1987-05-01

    The objectives of this study were to investigate the absorption of diazepam applied topically to the hairless mouse in vivo and to determine the diffusion of diazepam across isolated hairless mouse skin and human skin. (/sup 14/C)Diazepam was readily absorbed after topical administration to the intact hairless mouse, a total of 75.8% of the /sup 14/C-label applied being recovered in urine and feces. Diazepam was found to diffuse across human and hairless mouse skin unchanged in experiments with twin-chambered diffusion cells. The variation in diffusion rate or the flux for both human and mouse tissues was greater among specimens than between duplicate or triplicate trials for a single specimen. Fluxes for mouse skin (stratum corneum, epidermis, and dermis) were greater than for human skin (stratum corneum and epidermis): 0.35-0.61 microgram/cm2/h for mouse skin vs 0.24-0.42 microgram/cm2/h for human skin. The permeability coefficients for mouse skin ranged from 1.4-2.4 X 10(-2)cm/h compared with 0.8-1.4 X 10(-2)cm/h for human skin. Although human stratum corneum is almost twice the thickness of that of the hairless mouse, the diffusion coefficients for human skin were 3-12 times greater (0.76-3.31 X 10(-6) cm2/h for human skin vs 0.12-0.27 X 10(-6) cm2/h for hairless mouse) because of a shorter lag time for diffusion across human skin. These differences between the diffusion coefficients and diffusion rates (or permeability coefficients) suggest that the presence of the dermis may present some barrier properties. In vitro the dermis may require complete saturation before the diazepam can be detected in the receiving chamber.

  6. Hairless is a nuclear receptor corepressor essential for skin function

    PubMed Central

    Thompson, Catherine C.

    2009-01-01

    The activity of nuclear receptors is modulated by numerous coregulatory factors. Corepressors can either mediate the ability of nuclear receptors to repress transcription, or can inhibit transactivation by nuclear receptors. As we learn more about the mechanisms of transcriptional repression, the importance of repression by nuclear receptors in development and disease has become clear. The protein encoded by the mammalian Hairless (Hr) gene was shown to be a corepressor by virtue of its functional similarity to the well-established corepressors N-CoR and SMRT. Mutation of the Hr gene results in congenital hair loss in both mice and men. Investigation of Hairless function both in vitro and in mouse models in vivo has revealed a critical role in maintaining skin and hair by regulating the differentiation of epithelial stem cells, as well as a putative role in regulating gene expression via chromatin remodeling. PMID:20087431

  7. Evaluation of seven sunscreens on hairless mouse skin

    SciTech Connect

    Walter, J.F.

    1981-01-01

    The ability of seven sunscreens to protect against ultraviolet (UV)--induced inhibition of epidermal DNA synthesis was evaluated in vivo using a hairless mouse model. There were statistically significant differences among sunscreens in their ability to prevent UV-B (290 to 320 nm) inhibition of DNA synthesis. The protective factor (PF) of a sunscreen was arbitrarily defined as the ratio of the dose required to inhibit DNA synthesis by 50% with and without a sunscreen. The following PF values were determined: Coppertone 4, 4.4; Sundown Extra Protection, 8.4; Supershade 15, 21.0; Eclipse 15, 22.2; Blockout 15, 22.4; and Bain de Soleil 15, 27.6. Zinc oxide ointment protected against any significant suppression of DNA synthesis at all UV-B doses used. There was a relatively good correlation between the PF and the sun protection factor (SPF) claimed for each sunscreen by the manufacturer. However, the PF values determined in mouse skin were generally higher than the SPF values measured in human skin. Further studies are needed to determine if sunscreen substantivity (resistance to removal by water) can be evaluated by this technique.

  8. Iontophoretic transdermal delivery of buspirone hydrochloride in hairless mouse skin.

    PubMed

    Al-Khalili, Mohammad; Meidan, Victor M; Michniak, Bozena B

    2003-01-01

    The transdermal delivery of buspirone hydrochloride across hairless mouse skin and the combined effect of iontophoresis and terpene enhancers were evaluated in vitro using Franz diffusion cells. Iontophoretic delivery was optimized by evaluating the effect of drug concentration, current density, and pH of the vehicle solution. Increasing the current density from 0.05 to 0.1 mA/cm2 resulted in doubling of the iontophoretic flux of buspirone hydrochloride, while increasing drug concentration from 1% to 2% had no effect on flux. Using phosphate buffer to adjust the pH of the drug solution decreased the buspirone hydrochloride iontophoretic flux relative to water solutions. Incorporating buspirone hydrochloride into ethanol:water (50:50 vol/vol) based gel formulations using carboxymethylcellulose and hydroxypropylmethylcellulose had no effect on iontophoretic delivery. Incorporation of three terpene enhancers (menthol, cineole, and terpineol) into the gel resulted in a synergistic effect when combined with iontophoresis. Menthol was the most active enhancer, and when combined with iontophoresis it was possible to deliver 10 mg/cm2/day of buspirone hydrochloride.

  9. Transdermal iontophoresis of hydromorphone across hairless rat skin in vitro.

    PubMed

    Kumar, Maansi G; Lin, Senshang

    2009-01-01

    The feasibility of delivering hydromorphone by transdermal iontophoresis to obtain therapeutically effective analgesic concentrations for the management of cancer-related pain was evaluated. Anodal iontophoresis was performed, and the effect of current strength, current duration, solution pH, presence of buffer ions, and drug concentration on the transdermal permeation of hydromorphone was investigated in vitro. Freshly excised full-thickness hairless rat skin and side-by-side permeation cells connected to the Phoresor II with Ag/AgCl electrodes was used. The flux of hydromorphone was observed to significantly increase (P < 0.05) from 72.04-280.30 microg/cm(2)/h with increase in current strength from 0.10-0.50 mA. A linear relationship was obtained between hydromorphone flux and current strength. Furthermore, the flux of hydromorphone was influenced by solution pH and presence of buffer ions. Also, the in vitro permeation flux of hydromorphone was observed to significantly increase (P < 0.05) with a 10-fold increase in hydromorphone hydrochloride concentration from 0.01-0.10 M. However, with further increase to 0.50 M, there was no significant difference in flux. These results show that by manipulating electronic and formulation variables, the transdermal iontophoretic delivery of hydromorphone can be controlled, and therapeutically effective concentrations of hydromorphone for the management of cancer-related pain can be obtained.

  10. Confocal Raman Microspectroscopy: The Measurement of VX Depth Profiles in Hairless Guinea Pig Skin and the Evaluation of RSDL

    DTIC Science & Technology

    2015-02-01

    USAMRICD-TR-15-01 Confocal Raman Microspectroscopy: The Measurement of VX Depth Profiles in Hairless Guinea Pig Skin and the Evaluation...5a. CONTRACT NUMBER guinea pig skin and the evaluation of RSDL 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Braue, EH...upper skin layers of hairless guinea pigs and to determine the ability of Reactive Skin Decontamination Lotion (RSDL) to remove or degrade VX from

  11. Far-infrared suppresses skin photoaging in ultraviolet B-exposed fibroblasts and hairless mice

    PubMed Central

    Chiu, Hui-Wen; Chen, Cheng-Hsien; Chen, Yi-Jie; Hsu, Yung-Ho

    2017-01-01

    Ultraviolet (UV) induces skin photoaging, which is characterized by thickening, wrinkling, pigmentation, and dryness. Collagen, which is one of the main building blocks of human skin, is regulated by collagen synthesis and collagen breakdown. Autophagy was found to block the epidermal hyperproliferative response to UVB and may play a crucial role in preventing skin photoaging. In the present study, we investigated whether far-infrared (FIR) therapy can inhibit skin photoaging via UVB irradiation in NIH 3T3 mouse embryonic fibroblasts and SKH-1 hairless mice. We found that FIR treatment significantly increased procollagen type I through the induction of the TGF-β/Smad axis. Furthermore, UVB significantly enhanced the expression of matrix metalloproteinase-1 (MMP-1) and MMP-9. FIR inhibited UVB-induced MMP-1 and MMP-9. Treatment with FIR reversed UVB-decreased type I collagen. In addition, FIR induced autophagy by inhibiting the Akt/mTOR signaling pathway. In UVB-induced skin photoaging in a hairless mouse model, FIR treatment resulted in decreased skin thickness in UVB irradiated mice and inhibited the degradation of collagen fibers. Moreover, FIR can increase procollagen type I via the inhibition of MMP-9 and induction of TGF-β in skin tissues. Therefore, our study provides evidence for the beneficial effects of FIR exposure in a model of skin photoaging. PMID:28301572

  12. Oral Administration of Fermented Soymilk Products Protects the Skin of Hairless Mice against Ultraviolet Damage

    PubMed Central

    Kano, Mitsuyoshi; Kubota, Norihiro; Masuoka, Norie; Hori, Tetsuji; Miyazaki, Kouji; Ishikawa, Fumiyasu

    2016-01-01

    The protective effect of isoflavones on skin damage from ultraviolet (UV) radiation and their bioavailability were investigated in ovariectomized hairless mice fed diets composed of fermented soymilk containing aglycone forms of isoflavones or control soymilk containing glucose-conjugated forms of isoflavones. The erythema intensity of dorsal skin was significantly higher in ovariectomized mice than in sham-operated mice (p < 0.05). The erythema intensity and epidermal thickness of dorsal skin were significantly lower in the fermented soymilk diet group than in the control diet group (each p < 0.05). Levels of cyclobutane pyrimidine dimers in dorsal skin were significantly lower in the fermented soymilk diet group than in the control group (p < 0.05). Serum and dorsal skin isoflavone concentrations were significantly higher in the fermented soymilk diet group than in the soymilk diet group (p < 0.05). These results indicate that oral administration of a fermented soymilk diet increases isoflavone concentrations in the blood and skin, effectively scavenging the reactive oxygen species generated by UV irradiation and exerting an estrogen-like activity, with a consequent protective effect on skin photodamage in hairless mice. PMID:27556484

  13. Intraperitoneally administered biliverdin protects against UVB-induced skin photo-damage in hairless mice.

    PubMed

    Bai, Bingxue; Liu, Yingdi; You, Yan; Li, Yuzhen; Ma, Liangjuan

    2015-03-01

    Oxidative stress is shown to be responsible for ultraviolet B (UVB) irradiation-induced skin cancer and premature aging. Biliverdin (BVD), a product of heme oxygenase-1, has strong anti-oxidant and anti-inflammatory properties. In the present study, we investigated the effects of BVD on UVB-induced skin photo-damage in hairless mice. Mice were divided into three groups: control group, UVB group (only UVB irradiation) and BVD+UVB group (mice were intraperitoneally injected with BVD before each UVB irradiation). Intraperitoneal BVD injection resulted in a significant photoprotective effect by reducing morphological and histopathological changes to the skin. BVD also exhibited a significant antioxidant effect by increasing the superoxide dismutase (SOD) level and decreasing the thiobarbituric acid reactive substances (TBARS) level compared with the control group. In addition, BVD activated biliverdin reductase (BVR) expression and inhibited the UVB-induced increase of p38 mitogen-activated protein kinase phosphorylation (p-p38MAPK), MMP (matrix metalloproteinase)-1 and MMP-3 expression (p<0.05). It also significantly decreased the interleukin (IL)-6 level compared with the UVB group (p<0.05). In conclusion, these data suggest that the intraperitoneally administered BVD can prevent UVB irradiation-induced skin photo-damage in hairless mice and that this is likely mediated by its antioxidant and anti-inflammatory mechanisms and cell signal regulatory action.

  14. Effect of Sulfur Mustard on Mast Cells in Hairless Guinea Pig Skin

    DTIC Science & Technology

    1993-05-13

    AD-P008 756 EFFECT OF SULFUR MUSTARD ON MAST CELLS IN HAIRLESS GUINEA PIG SKIN JOHN S. GRAHAM, MARK A . BRYANT and ERNEST H. BRAUE U.S. Army Medical...with their granules of vasoactive histamine, mast cells might be expected to play a role in HD-induced injury. Changes in mast cells exposed to low...histopathology 94-07918 Best Available Copy C0t PONENT PART NOTICE THIS PAPER IS A CCWPOWENT PART OF THE FOLLOWING COIPILATION REPORT: TITLE: Proceedins of the

  15. Circadian rhythms on skin function of hairless rats: light and thermic influences.

    PubMed

    Flo, Ana; Díez-Noguera, Antoni; Calpena, Ana C; Cambras, Trinitat

    2014-03-01

    Circadian rhythms are present in most functions of living beings. We have demonstrated the presence of circadian rhythms in skin variables (transepidermal water loss, TEWL; stratum corneum hydration, SCH; and skin temperature) in hairless rats under different environmental conditions of light and temperature. Circadian rhythms in TEWL and SCH showed mean amplitudes of about 20% and 14% around the mean, respectively, and appeared under light-dark cycles as well as under constant darkness. Environmental temperature was able to override TEWL, but not SCH rhythm, evidencing the dependency of TEWL on the temperature. Mean daily values of TEWL and SCH, and also the amplitude of TEWL rhythm, increased with the age of the animal. Under constant light, situation that induces arrhythmicity in rats, SCH and TEWL were inversely correlated. The results suggest the importance to take into account the functional skin rhythms in research in dermatological sciences.

  16. Oral intake of beet extract provides protection against skin barrier impairment in hairless mice.

    PubMed

    Kawano, Ken-Ichi; Umemura, Kazuo

    2013-05-01

    The epidermis acts as a functional barrier against the external environment. Disturbances in the function of this barrier cause water loss and increase the chances of penetration by various irritable stimuli, leading to skin diseases such as dry skin, atopic dermatitis, and psoriasis. Ceramides are a critical natural element of the protective epidermal barrier. The aim of this study was to evaluate whether the oral intake of beet (Beta vulgaris) extract, a natural product rich in glucosylceramide (GlcCer), may prevent disturbance in skin barrier function. When HR-1 hairless mice were fed a special diet (HR-AD), transepidermal water loss (TEWL) from the dorsal skin increased, with a compensatory increase in water intake after 5 weeks. Mice fed with HR-AD had dry skin with erythema and showed increased scratching behaviour. Histological examinations revealed a remarkable increase in the thickness of the skin at 8 weeks. Supplemental addition of beet extract, which contained GlcCer at a final concentration of 0.1%, significantly prevented an increase TEWL, water intake, cumulative scratching time, and epidermal thickness at 8 weeks. These results indicate that oral intake of beet extract shows potential for preventing skin diseases associated with impaired skin barrier function.

  17. Effect of sulfur mustard on mast cells in hairless guinea pig skin

    SciTech Connect

    Graham, J.S.; Bryant, M.A.; Braue, E.H.

    1993-05-13

    The skin of 24 anesthetized hairless guinea pigs was exposed to saturated sulfur mustard (bis-2-chloroethyl sulfide; HD) for 5 and 7 minutes using 14-mm diameter vapor cups. Animals were euthanatized 24 hours after exposure and skin specimens taken for morphometric evaluation of granulated mast cells with an image analysis system (IAS). Tissue specimens were processed in paraffin, sectioned at 5 microns and stained with Unna's stain for mast cells. The number of granulated mast cells and the area occupied by mast cell granules was determined. There were significantly fewer mast cells (p < 0.05) in either HD exposure group than in sham-exposed animals, with significantly fewer mast cells in the 7-minute than the 5-minute HD group. There were also significantly smaller areas occupied by granules in either HD exposure group than in sham-exposed animals. HD-induced lesions in the hairless guinea pig have shown signs of an inflammatory response, and with their granules of vasoactive histamine, mast cells might be expected to play a role in HD-induced injury. Changes in mast cells exposed to low sulfur mustard levels, as detected by an IAS, may serve as an early marker for cutaneous damage, which might not be as easily determined with routine light microscopy.

  18. Effect of microplasma irradiation on skin barrier function

    NASA Astrophysics Data System (ADS)

    Shimizu, Kazuo; Tran, An N.; Blajan, Marius

    2016-07-01

    In this paper, we introduce the feasibility of atmospheric-pressure argon microplasma irradiation (AAMI) to promote percutaneous absorption. A hairless Yucatan micropig skin was used for this ex vivo study. After AAMI, the disturbance in the stratum corneum (SC) lipids was observed using attenuated total reflectance-Fourier transform infrared spectroscopy. Also, an increase in transepidermal water loss and no physical damage on pig skins were confirmed by microscopic observation. These results of AAMI were compared with those of a plasma jet irradiation (PJI) and a tape stripping test (TST) leading to the conclusion that AAMI reduces the barrier function of the skin and could also enhance the transdermal absorption of drugs.

  19. Sunless skin tanning with dihydroxyacetone delays broad-spectrum ultraviolet photocarcinogenesis in hairless mice.

    PubMed

    Petersen, Anita B; Na, Renhua; Wulf, Hans Christian

    2003-12-09

    Sunless tanning with dihydroxyacetone (DHA) is not considered to be a sunscreen although it does absorb parts of the ultraviolet (UV) spectrum. We investigated the protection with topical application of DHA against solar UV-induced skin carcinogenesis in lightly pigmented hairless hr/hr C3H/Tif mice. Broad-spectrum UV radiation, simulating the UV part of the solar spectrum was obtained from one Philips TL12 and five Bellarium-S SA-1-12 tubes. Three groups of mice were UV-exposed four times a week to a dose-equivalent of four times the standard erythema dose (SED), without or with application of 5 or 20% DHA only twice a week. Similarly, three groups of mice were treated with DHA and irradiated with a high UV dose (8 SED), simulating a skin burn. Two groups (controls) were not irradiated, but either left untreated or treated with 20% DHA alone. The UV-induced skin pigmentation by melanogenesis could easily be distinguished from DHA-induced browning and was measured by a non-invasive, semi-quantitative method. Application of 20% DHA reduced by 63% the pigmentation produced by 4 SED, however, only by 28% the pigmentation produced by 8 SED. Furthermore, topical application of 20% DHA significantly delayed the time to appearance of the first tumor >or=1mm (P=0.0012) and the time to appearance of the third tumor (P=2 x 10(-6)) in mice irradiated with 4 SED. However, 20% DHA did not delay tumor development in mice irradiated with 8 SED. Application of 5% DHA did not influence pigmentation or photocarcinogenesis. In conclusion, this is the first study to show that the superficial skin coloring generated by frequent topical application of DHA in high concentrations may delay skin cancer development in hairless mice irradiated with moderate UV doses.

  20. Collagen metabolism in ultraviolet irradiated hairless mouse skin and its correlation to histochemical observations.

    PubMed

    Kligman, L H; Gebre, M; Alper, R; Kefalides, N A

    1989-08-01

    Early biochemical studies of ultraviolet (UV) irradiated human skin reported a loss of insoluble collagen with a concomitant increase in the soluble fraction. Recent work has described an early increase in type III collagen during chronic irradiation of hairless mice as determined by cyanogen bromide digests of whole skin. In order to understand the correlation of these events and those seen with histochemistry, in the present study we irradiated hairless mice for up to 24 weeks with approximately 4 minimal erythema doses (MEDs) of UVB thrice weekly with Westinghouse FS-40 bulbs. Skin samples were taken at 4-week intervals from irradiated and age-matched control mice. Collagen was isolated from other skin proteins by acid extraction, pepsin digestion, and salt precipitation. Estimates of types I and III collagen were made by interrupted polyacrylamide gel electrophoresis and densitometric scanning. Compared with unirradiated controls, there was a small increase in the ratio of type III to total collagen after 8 weeks of UV. There were no significant increases at later time points until after 24 weeks of radiation. Total collagen in normal mouse skin, determined by hydroxyproline content, remained constant over the 24 weeks, while UV radiation produced significant increases at 4, 8, 12, and 16 weeks, returning to control levels at week 20. There was no change in the degree of hydroxylation at any time point in either group. Thus, chronic UV exposure resulted in increased collagen synthesis until late in the course of irradiation. Because there is a lack of consistent change in the ratio of type III to total collagen, the early increases in collagen content may represent both types I and III, synthesized in relatively unchanging proportions.

  1. Naringenin Inhibits UVB Irradiation-Induced Inflammation and Oxidative Stress in the Skin of Hairless Mice.

    PubMed

    Martinez, Renata M; Pinho-Ribeiro, Felipe A; Steffen, Vinicius S; Caviglione, Carla V; Vignoli, Josiane A; Barbosa, Décio S; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rubia

    2015-07-24

    Ultraviolet B (UVB) irradiation may cause inflammation- and oxidative-stress-dependent skin cancer and premature aging. Naringenin (1) has been reported to have anti-inflammatory and antioxidant properties, but its effects and mechanisms on UVB irradiation-induced inflammation and oxidative stress are still not known. Thus, the present study aimed to investigate the potential of naringenin to mitigate UVB irradiation-induced inflammation and oxidative damage in the skin of hairless mice. Skin edema, myeloperoxidase (neutrophil marker) and matrix metalloproteinase-9 (MMP-9) activity, and cytokine production were measured after UVB irradiation. Oxidative stress was evaluated by 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS) scavenging ability, ferric reducing antioxidant power (FRAP), reduced glutathione levels, catalase activity, lipid peroxidation products, superoxide anion production, and gp91phox (NADPH oxidase subunit) mRNA expression by quantitative PCR. The intraperitoneal treatment with naringenin reduced skin inflammation by inhibiting skin edema, neutrophil recruitment, MMP-9 activity, and pro-inflammatory (TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-12, IL-13, IL-17, IL-22, and IL-23) and anti-inflammatory (TGF-β and IL-10) cytokines. Naringenin also inhibited oxidative stress by reducing superoxide anion production and the mRNA expression of gp91phox. Therefore, naringenin inhibits UVB irradiation-induced skin damage and may be a promising therapeutic approach to control skin disease.

  2. Changes in arachidonic acid metabolism in UV-irradiated hairless mouse skin

    SciTech Connect

    Ruzicka, T.; Walter, J.F.; Printz, M.P.

    1983-10-01

    This study was conducted to investigate the metabolism of arachidonic acid in the skin of hairless mice exposed to UVA, PUVA, UVB, and UVC irradiation. The main products of arachidonic acid in the epidermis were hydroxyeicosatetraenoic acid (HETE), PGE2, and PGD2. Dermis displayed a lower lipoxygenase activity (expressed as HETE production) than the epidermis and showed no detectable cyclooxygenase activity, i.e., no prostaglandin production. The main changes observed in UV-induced inflammatory reactions were as follows. 1. A 5-fold increase in dermal HETE production in PUVA-treated animals and a 29% reduction in epidermal HETE formation after UVC treatment. 2. A marked decrease of PGD2 and a marked increase of PGE2 formation due to alterations of PGH2 metabolism in the UVB-treated group; however, cyclooxygenase activity was unchanged. These changes in arachidonic acid metabolism in the skin may be of pathophysiologic importance in UV-induced inflammatory reaction.

  3. Iontophoresis itself on hairless mouse skin induces the loss of the epidermal calcium gradient without skin barrier impairment.

    PubMed

    Lee, S H; Choi, E H; Feingold, K R; Jiang, S; Ahn, S K

    1998-07-01

    Iontophoresis increases the delivery of drugs across the stratum corneum, but the pathway by which ionized drugs transit the stratum corneum is unknown. In this study we examined the effect of iontophoresis on the skin barrier and the epidermal calcium gradient. Hairless mice were subjected to iontophoresis for 5-120 min and skin specimens were prepared for electron microscopy. Neither positive nor negative iontophoresis affected transepidermal water loss. Lacunar dilatation and partial distention of the intercellular layers of the stratum corneum were observed in rough proportion to applied time in iontophoresis skin as well as control skin. Additionally, using calcium capture cytochemistry, we demonstrated that both positive and negative iontophoresis caused the disappearance of the epidermal calcium gradient with marked decrease in calcium content in the upper epidermis. Positive iontophoresis was associated with increased calcium in the stratum basale and dermis, whereas negative iontophoresis increased calcium in the stratum corneum. Moreover, as previously shown after barrier disruption and sonophoresis, the decrease in calcium content in the upper epidermis was associated with an increase in lamellar body secretion and the build up of lamellar material at the stratum corneum-stratum granulosum interface. In conclusion, iontophoresis on the skin of hairless mice may induce the change of ionized molecules in the epidermis, as the loss of the calcium gradient, which causes the decrease of skin impedence, gives charged drugs the ability to cross the skin more easily. Also, the structural changes, such as lacunar dilatation, whether they result from hydration or occlusion, may help the transport of charged drugs across the stratum corneum.

  4. Photodynamic therapy induces epidermal thickening in hairless mice skin: an optical coherence tomography assessment

    NASA Astrophysics Data System (ADS)

    Jorge, Ana Elisa S.; Campos, Carolina P.; Freitas, Anderson Z.; Bagnato, Vanderlei S.

    2014-03-01

    Photodynamic therapy (PDT) promotes skin improvement according to many practitioners, however the immediately in vivo assessment of its response remains clinically inaccessible. As a non-invasive modality, optical coherence tomography (OCT) has been shown a feasible optical diagnostic technique that provides images in real time, avoiding tissue biopsies. For this reason, our investigation focused on evaluates the PDT effect on a rodent model by means of OCT. Therefore, a normal hairless mouse skin has undergone a single-session PDT, which was performed with topical 5- aminolevulinic acid (ALA) cream using a red (630 nm) light emitting diode (LED) which reached the light dose of 75 J/cm2. As the optical imaging tool, an OCT (930 nm) with axial resolution of 6.0 microns in air was used, generating images with contact to the mouse skin before, immediately after, 24 hours, and 2 weeks after the correspondent procedure. Our result demonstrates that, within 24 hours after ALA-PDT, the mouse skin from the PDT group has shown epidermal thickness (ET), which has substantially increased after 2 weeks from the treatment day. Moreover, the skin surface has become evener after ALA-PDT. Concluding, this investigation demonstrates that the OCT is a feasible and reliable technique that allows real-time cross-sectional imaging of skin, which can quantify an outcome and predict whether the PDT reaches its goal.

  5. Topical tretinoin increases the tropoelastin and fibronectin content of photoaged hairless mouse skin.

    PubMed

    Schwartz, E; Kligman, L H

    1995-04-01

    Topical tretinoin treatment of photoaged hairless mice has been shown in previous studies to stimulate formation of a subepidermal zone of new connective tissue characterized by enhanced collagen synthesis. The aims of this study were to localize and/or quantify elastin, fibronectin, and glycosaminoglycans in the same model. Hairless mice (Skh-1) were irradiated thrice weekly for 10 weeks with gradually increasing doses of ultraviolet (up to 4.5 minimal erythema doses per exposure) from Westinghouse FS-40 bulbs. Mice were then treated five times a week with either 0.05% tretinoin, the ethanol:propylene glycol vehicle, or nothing for another 10 weeks. Controls included mice sacrificed after 10 weeks of ultraviolet treatment and age-matched untreated animals. The distribution of elastin and fibronectin was examined by immunofluorescence microscopy, which revealed fine fibrils in the subepidermal zone in tretinoin-treated skin. A quantitative slot-blot immunobinding assay showed that tretinoin induced a threefold higher amount of tropoelastin compared with controls. Insoluble elastin content (desmosine levels) was similar in all groups. Although fibronectin content was increased by ultraviolet radiation, tretinoin treatment induced the largest increase. In contrast, the amount of glycosaminoglycans, although increased by UVB radiation, was reduced by tretinoin treatment.

  6. Preventive effect of dietary astaxanthin on UVA-induced skin photoaging in hairless mice

    PubMed Central

    Komatsu, Toshiyuki; Sasaki, Suguru; Manabe, Yuki; Hirata, Takashi

    2017-01-01

    Astaxanthin, a carotenoid found mainly in seafood, has potential clinical applications due to its antioxidant activity. In this study, we evaluated the effect of dietary astaxanthin derived from Haematococcus pluvialis on skin photoaging in UVA-irradiated hairless mice by assessing various parameters of photoaging. After chronic ultraviolet A (UVA) exposure, a significant increase in transepidermal water loss (TEWL) and wrinkle formation in the dorsal skin caused by UVA was observed, and dietary astaxanthin significantly suppressed these photoaging features. We found that the mRNA expression of lympho-epithelial Kazal-type-related inhibitor, steroid sulfatase, and aquaporin 3 in the epidermis was significantly increased by UVA irradiation for 70 days, and dietary astaxanthin significantly suppressed these increases in mRNA expression to be comparable to control levels. In the dermis, the mRNA expression of matrix metalloprotease 13 was increased by UVA irradiation and significantly suppressed by dietary astaxanthin. In addition, HPLC-PDA analysis confirmed that dietary astaxanthin reached not only the dermis but also the epidermis. Our results indicate that dietary astaxanthin accumulates in the skin and appears to prevent the effects of UVA irradiation on filaggrin metabolism and desquamation in the epidermis and the extracellular matrix in the dermis. PMID:28170435

  7. Ultrastructural demonstration of chemical modification of melanogenesis in hairless mouse skin

    SciTech Connect

    Nishimura, M.; Gellin, G.A.; Hoshino, S.; Epstein, J.H.; Epstein, W.L.; Fukuyama, K.

    1982-02-01

    We investigated chemical and physical modifications of the genetically determined ultrastructure of melanosomes. The flank skin of hairless mice was treated with ultraviolet energy (UV) shorter than 320 nm or with a combination of a photosensitizer and UV (PUVA treatment). All melanosomes in the induced melanocytes and those in resident melanocytes in the ear skin showed eumelanogenesis, although the degree of melanin deposition differed considerably according to the induction process. Eumelanogenesis was most advanced in the resident melanocytes while PUVA-induced melanocytes showed more immature premelanosomes. We then topically applied 4-tertiary butyl catechol on the skin. The depigmenting agent caused an appearance of pheomelanosomes. The alteration in melanogenesis was seen most distinctly in premelanosomes of the PUVA-induced cells. Altered ultrastructure was also observed in matured melanosomes; this change was most apparent in the resident melanocytes. These findings indicate that cells with eumelanogenesis may undergo pheomelanogenesis. The present study demonstrated effects of chemicals on genetically determined function of melanocytes by quantitative analysis of melanosome ultrastructure.

  8. Codiffusion of propylene glycol and dimethyl isosorbide in hairless mouse skin.

    PubMed

    Squillante, E; Needham, T; Maniar, A; Kislalioglu, S; Zia, H

    1998-11-01

    The in vitro percutaneous fluxes of propylene glycol (PG), cis-oleic acid (OA) and dimethyl isosorbide (DI) were determined and their effect on nifedipine (N) flux and lag time evaluated. PG, OA and DI flux through hairless mouse (HM) skin was measured in vitro by beta-scintigraphy and N permeation was measured by HPLC under finite and infinite dose conditions. Evaluation of each of the solvents separately showed that pure DI possessed the inherent ability to traverse the skin (12% in 24 h). For the tested formulation after 24 h, 57% of the PG and 40% of the DI had permeated across the skin with nearly linear permeation between 4 and 18 h and the relative order of permeation was PG > DI > N. DI permeation was further aided in the presence of PG and OA. N flux was dependent on concomitant solvent permeation. Over a 24-h test period a dose dependent response was observed for N, with 4.9-15.6 mg of N delivered from the lowest and highest doses, respectively, and the highest dose yielding zero-order flux of 146 (g/h per cm2).

  9. Effects of Porcine Placenta Extract Ingestion on Ultraviolet B-induced Skin Damage in Hairless Mice

    PubMed Central

    Hong, Ki-Bae; Park, Yooheon; Kim, Jae Hwan; Kim, Jin Man; Suh, Hyung Joo

    2015-01-01

    The aim of our study was to evaluate the potential benefits of an oral supplement containing porcine placenta extract (PPE) on skin parameters related to cutaneous physiology and aging. PPEs were administered orally to hairless mice for 12 wk. The effects of oral PPE administration on skin water-holding capacity and Transepidermal Water Loss (TEWL) were similar to those of oral collagen (HYCPU2) administered as a positive control. Magnified photographs and replica images showed a reduction in UVB-induced wrinkle formation after collagen and PPE treatments. PPE treatments ameliorated the thicker skin surface that results from UVB exposure, based on a histological examination of skin tissue. The groups that were orally administered PPE (0.05%, OL; 0.1%, OH group) showed significantly reduced Matrix Metaloproteinase-2 (MMP-2) mRNA expression levels compared with the UVB control (Con), by 33.5% and 35.2%, respectively. The mRNA expression of another collagen-degrading protein, MMP-9, was also significantly lower in the groups that received oral administration of PPE (especially in the OH group) than in the control group. Additionally, oral administration of PPE significantly upregulated tissue inhibitor of metalloproteinase-1 (TIMP-1) and -2 mRNA expression levels compared with expression levels in the control group (p<0.05). This indicates that orally administered PPE activated the expression of Timp-1 and -2, inhibitors of MMP, which is responsible for collagen degradation in skin. Taken together, we propose that long-term oral administration of PPE might have a beneficial effect with respect to skin photo-aging. PMID:26761856

  10. Comparison of fixation and processing methods for hairless guinea pig skin following sulfur mustard exposure. (Reannouncement with new availability information)

    SciTech Connect

    Bryant, M.A.; Braue Jr, E.H.

    1992-12-31

    Ten anesthetized hairless guinea pigs Crl:IAF(HA)BR were exposed to 10 pi of neat sulfur mustard (HD) in a vapor cup on their skin for 7 min. At 24 h postexposure, the guinea pigs were euthanatized and skin sections taken for histologic evaluation. The skin was fixed using either 10% neutral buffered formalin (NBF), McDowell Trump fixative (4CF-IG), Zenker`s formol-saline (Helly`s fluid), or Zenker`s fluid. Fixed skin sections were cut in half: one half was embedded in paraffin and the other half in plastic (glycol methacrylate). Paraffin-embedded tissue was stained with hematoxylin and eosin; plastic-embedded tissue was stained with Lee`s methylene blue basic fuchsin. Skin was also frozen unfixed, sectioned by cryostat, and stained with pinacyanole. HD-exposed skin was evaluated histologically for the presence of epidermal and follicular necrosis, microblister formation, epidermitis, and intracellular edema to determine the optimal fixation and embedding method for lesion preservation. The percentage of histologic sections with lesions varied little between fixatives and was similar for both paraffin and plastic embedding material. Plastic-embedded sections were thinner, allowing better histologic evaluation, but were more difficult to stain. Plastic embedding material did not infiltrate tissue fixed in Zenker`s fluid or Zenker`s formol-saline. Frozen tissue sections were prepared in the least processing time and lesion preservation was comparable to fixed tissue. It was concluded that standard histologic processing using formalin fixation and paraffin embedding is adequate for routine histopathological evaluation of HD skin lesions in the hairless guinea pig.... Sulfur mustard, Vesicating agents, Pathology, Hairless guinea pig model, Fixation.

  11. SKHIN/Sprd, a new genetically defined inbred hairless mouse strain for UV-induced skin carcinogenesis studies

    PubMed Central

    Perez, Carlos; Parker-Thornburg, Jan; Mikulec, Carol; Kusewitt, Donna F.; Fischer, Susan M.; DiGiovanni, John; Conti, Claudio J.; Benavides, Fernando

    2013-01-01

    Strains of mice vary in their susceptibility to ultra-violet (UV) radiation-induced skin tumors. Some strains of hairless mice (homozygous for the spontaneous Hrhr mutation) are particularly susceptible to these tumors. The skin tumors that develop in hairless mice resemble, both at the morphologic and molecular levels, UV-induced squamous cell carcinomas (SCC) and their precursors in human. The most commonly employed hairless mice belong to the SKH1 stock. However, these mice are outbred and their genetic background is not characterized, which makes them a poor model for genetic studies. We have developed a new inbred strain from outbred SKH1 mice that we named SKHIN/Sprd (now at generation F31). In order to characterize the genetic background of this new strain, we genotyped a cohort of mice at F30 with 92 microsatellites and 140 single nucleotide polymorphisms (SNP) evenly distributed throughout the mouse genome. We also exposed SKHIN/Sprd mice to chronic UV irradiation and showed that they are as susceptible to UV-induced skin carcinogenesis as outbred SKH1 mice. In addition, we proved that, albeit with low efficiency, inbred SKHIN/Sprd mice are suitable for transgenic production by classical pronuclear microinjection. This new inbred strain will be useful for the development of transgenic and congenic strains on a hairless inbred background as well as the establishment of syngeneic tumor cell lines. These new tools can potentially help elucidate a number of features of the cutaneous response to UV irradiation in humans, including the effect of genetic background and modifier genes. PMID:22379968

  12. Antiinflammatory and Antiphotodamaging Effects of Ergostatrien-3β-ol, Isolated from Antrodia camphorata, on Hairless Mouse Skin.

    PubMed

    Kuo, Yueh-Hsiung; Lin, Tzu-Yu; You, Ya-Jhen; Wen, Kuo-Ching; Sung, Ping-Jyun; Chiang, Hsiu-Mei

    2016-09-10

    Ergostatrien-3β-ol (EK100), isolated from the submerged whole broth of Antrodia camphorata, has antidiabetic, hyperlipidemic, and hepatoprotective activities. However, the antiphotodamage activity of EK100 has still not been revealed. Inflammation and collagen degradation contribute to skin photodamage and premature aging. In the present study, in vivo experiments were designed to investigate the antiinflammatory and antiphotodamaging activities of EK100 in hairless mice by physiological and histological analysis of the skin. Results indicated that topical application of EK100 (25 and 100 μM) for 10 weeks efficiently inhibited ultraviolet B (UVB)-induced wrinkle formation, erythema, and epidermal thickness in the mice skin. EK100 also restored UVB-induced collagen content reduction in hairless mice skin. In addition, the immunohistochemistry results indicated that EK100 significantly inhibited the UVB-induced expression of matrix metalloproteinase-1 (MMP-1), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and nuclear factor kappaB (NF-κB) in the mouse skin. The expression of these proteins was similar to the Normal group after 100 μM EK100 treatment. EK100 inhibited collagen degradation in the skin through MMP-1 inhibition and antiinflammation. EK100 significantly reduced the transepidermal water loss (TEWL), indicating that EK100 protected skin from UVB-induced damage. Our findings strongly suggest that EK100 has significant beneficial antiinflammatory and antiphotoaging activities and that EK100 can be developed as an antiphotodamaging agent.

  13. Estimation of neutrophil infiltration into hairless guinea pig skin treated with 2,2' -dichlorodiethyl sulfide

    SciTech Connect

    Bongiovanni, R.; Millard, C.B.; Schulz, S.M.; Romano, J.M.

    1993-05-13

    Despite growing acceptance of the hairless guinea pig (HPG) for evaluating sulfur mustard (2,2'dichlorodiethylsulfide, HD) skin injury, there are presently few antivesicant drug assessment endpoints validated in vivo for this model. We measured the activity of myeloperoxidase (MPO) to characterize the dose- and time-dependence of polymorphonuclear leukocyte (PMN) infiltration during development of the HD lesion. Biopsies were obtained from the dorsal thoracic-lumbar area of HGPs at successive 3 hr time intervals for up to 24 hrs following controlled exposure to either 5, 7, 8 or 10 min HD vapor. The presence of PMNs, as judged by MPO levels, peaked at 9 hrs irrespective of total HD vapor dose. The maximum response was a 20-fold increase compared to unexposed control sites at 9 hrs following 10 min HD vapor. This time period coincides with epidermal detachment characterized previously by electron microscopy in the HGP. By 24 hrs post-exposure, the MPO levels subsided markedly (2-fold compared to controls). These results suggest that PMNs participate in the HGP cutaneous inflammatory response following exposure to HD and that MPO may be a useful biological marker for evaluating putative antivesicants.

  14. Acerola (Malpighia emarginata DC.) Juice Intake Suppresses UVB-Induced Skin Pigmentation in SMP30/GNL Knockout Hairless Mice

    PubMed Central

    Sato, Yasunori; Uchida, Eriko; Aoki, Hitoshi; Hanamura, Takayuki; Nagamine, Kenichi; Kato, Hisanori; Koizumi, Takeshi

    2017-01-01

    Background/Aims Acerola (Malpighia emarginata DC.) is a fruit that is known to contain high amounts of ascorbic acid (AA) and various phytochemicals. We have previously reported that AA deficiency leads to ultraviolet B (UVB)-induced skin pigmentation in senescence marker protein 30 (SMP30)/gluconolactonase (GNL) knockout (KO) hairless mice. The present study was undertaken to investigate the effects of acerola juice (AJ) intake on the skin of UVB-irradiated SMP30/GNL KO mice. Research design/Principal findings Five-week old hairless mice were given drinking water containing physiologically sufficient AA (1.5 g/L) [AA (+)], no AA [AA (-)] or 1.67% acerola juice [AJ]. All mice were exposed to UVB irradiation for 6 weeks. UVB irradiation was performed three times per week. The dorsal skin color and stratum corneum water content were measured every weekly, and finally, the AA contents of the skin was determined. The skin AA and stratum corneum water content was similar between the AA (+) and AJ groups. The L* value of the AA (+) group was significantly decreased by UVB irradiation, whereas AJ intake suppressed the decrease in the L* value throughout the experiment. Moreover, in the AJ group, there was a significant decrease in the expression level of dopachrome tautomerase, an enzyme that is involved in melanin biosynthesis. Conclusion These results indicate that AJ intake is effective in suppressing UVB-induced skin pigmentation by inhibiting melanogenesis-related genes. PMID:28114343

  15. Exopolysaccharides Isolated from Milk Fermented with Lactic Acid Bacteria Prevent Ultraviolet-Induced Skin Damage in Hairless Mice

    PubMed Central

    Morifuji, Masashi; Kitade, Masami; Fukasawa, Tomoyuki; Yamaji, Taketo; Ichihashi, Masamitsu

    2017-01-01

    Background: We studied the mechanism by which fermented milk ameliorates UV-B-induced skin damage and determined the active components in milk fermented with lactic acid bacteria by evaluating erythema formation, dryness, epidermal proliferation, DNA damage and cytokine mRNA levels in hairless mice exposed to acute UV-B irradiation. Methods: Nine week-old hairless mice were given fermented milk (1.3 g/kg BW/day) or exopolysaccharide (EPS) concentrate (70 mg/kg BW/day) orally for ten days. Seven days after fermented milk or EPS administration began, the dorsal skin of the mice was exposed to a single dose of UV-B (20 mJ/cm2). Results: Ingestion of either fermented milk or EPS significantly attenuated UV-B-induced erythema formation, dryness and epidermal proliferation in mouse skin. Both fermented milk and EPS were associated with a significant decrease in cyclobutane pyrimidine dimers and upregulated mRNA levels of xeroderma pigmentosum complementation group A (XPA), which is involved in DNA repair. Furthermore, administration of either fermented milk or EPS significantly suppressed increases in the ratio of interleukin (IL)-10/IL-12a and IL-10/interferon-gamma mRNA levels. Conclusion: Together, these results indicate that EPS isolated from milk fermented with lactic acid bacteria enhanced DNA repair mechanisms and modulated skin immunity to protect skin against UV damage. PMID:28098755

  16. Involvement of skin barrier dysfunction in itch-related scratching in special diet-fed hairless mice.

    PubMed

    Fujii, Masanori; Nabe, Takeshi; Tomozawa, Junko; Kohno, Shigekatsu

    2006-01-13

    HR-1 hairless mice fed with a special diet develop atopic-like dry skin, characterized by increased transepidermal water loss, and prolonged bouts of spontaneous scratching. In this study, the role of the skin barrier dysfunction in the prolongation of scratching was evaluated. Although the prolonged scratching was dose-dependently inhibited by opioid receptor antagonist naloxone, neither H(1) receptor antagonist, mepyramine, nor 5-HT(1/2) receptor antagonist, methysergide, affected it. Thus, the prolonged scratching could be itch-related response independent of histamine and serotonin. The application of petrolatum ointment on the skin temporarily alleviated the increase of transepidermal water loss for 60 min after treatment. Due to this alleviation in barrier dysfunction, the prolongation of scratching was significantly suppressed. However, when the barrier dysfunction relapsed, the scratching worsened. Taken together, a skin barrier dysfunction is associated with the itch-related response.

  17. Protective effect of fermented soybean dried extracts against TPA-induced oxidative stress in hairless mice skin.

    PubMed

    Georgetti, Sandra R; Casagrande, Rúbia; Vicentini, Fabiana T M C; Baracat, Marcela M; Verri, Waldiceu A; Fonseca, Maria J V

    2013-01-01

    This study evaluated the chemical properties (polyphenol and genistein contents) of soybean extracts obtained by biotransformation and dried by spray dryer at different conditions and their in vivo ability to inhibit 12-O-tetradecanoylphorbol-13-acetate- (TPA-) induced biochemical alterations in the skin of hairless mice. By comparing the obtained data with that of the well-known active soybean extract Isoflavin beta, we evaluated the influence of the fermentation and drying process in the extracts efficacy. The results demonstrated that inlet gas temperature and adjuvant concentration for the extract drying process have significantly affected the total polyphenol contents and, to a minor degree, the genistein contents. However, the effect of topical stimulus with TPA, an oxidative stress inducer, which caused significant depletion of reduced glutathione (GSH) and catalase, with increased levels of H2O2 and lipid peroxidation (MDA) in the skin of hairless mice, was significantly prevented by the soybean extracts treatment. These results indicate that the spray drying processing resulted in a product capable of limiting the oxidative stress with possible therapeutic applicability as an antioxidant in pharmaceutical forms.

  18. Protective Effect of Fermented Soybean Dried Extracts against TPA-Induced Oxidative Stress in Hairless Mice Skin

    PubMed Central

    Georgetti, Sandra R.; Casagrande, Rúbia; Vicentini, Fabiana T. M. C.; Baracat, Marcela M.; Verri, Waldiceu A.; Fonseca, Maria J. V.

    2013-01-01

    This study evaluated the chemical properties (polyphenol and genistein contents) of soybean extracts obtained by biotransformation and dried by spray dryer at different conditions and their in vivo ability to inhibit 12-O-tetradecanoylphorbol-13-acetate- (TPA-) induced biochemical alterations in the skin of hairless mice. By comparing the obtained data with that of the well-known active soybean extract Isoflavin beta, we evaluated the influence of the fermentation and drying process in the extracts efficacy. The results demonstrated that inlet gas temperature and adjuvant concentration for the extract drying process have significantly affected the total polyphenol contents and, to a minor degree, the genistein contents. However, the effect of topical stimulus with TPA, an oxidative stress inducer, which caused significant depletion of reduced glutathione (GSH) and catalase, with increased levels of H2O2 and lipid peroxidation (MDA) in the skin of hairless mice, was significantly prevented by the soybean extracts treatment. These results indicate that the spray drying processing resulted in a product capable of limiting the oxidative stress with possible therapeutic applicability as an antioxidant in pharmaceutical forms. PMID:24073399

  19. Inhibition of UVB-induced skin damage by exopolymers from Aureobasidium pullulans SM-2001 in hairless mice.

    PubMed

    Kim, Kyung Hu; Park, Soo Jin; Lee, Young Joon; Lee, Ji Eun; Song, Chang Hyun; Choi, Seong Hun; Ku, Sae Kwang; Kang, Su Jin

    2015-02-01

    Because antioxidants from natural sources may be an effective approach to the treatment and prevention of UV radiation-induced skin damage, the effects of purified exopolymers from Aureobasidium pullulans SM-2001 ('E-AP-SM2001') were evaluated in UVB-induced hairless mice. E-AP-SM2001 consists of 1.7% β-1,3/1,6-glucan, fibrous polysaccharides and other organic materials, such as amino acids, and mono- and di-unsaturated fatty acids (linoleic and linolenic acids) and shows anti-osteoporotic and immunomodulatory effects, through antioxidant and anti-inflammatory mechanisms. Hairless mice were treated topically with vehicle, E-AP-SM2001 stock and two and four times diluted solutions once per day for 15 weeks against UVB irradiation (three times per week at 0.18 J/cm(2) ). The following parameters were evaluated in skin samples: myeloperoxidase (MPO) activity, cytokine levels [interleukin (IL)-1β and IL-10], endogenous antioxidant content (glutathione, GSH), malondialdehyde (MDA) levels, superoxide anion production; matrix metalloproteases (MMP-1, -9 and -13), GSH reductase and Nox2 (gp91phox) mRNA levels, and immunoreactivity for nitrotyrosine (NT), 4-hydroxynonenal (HNE), caspase-3, and cleaved poly(ADP-ribose) polymerase (PARP). Photoageing was induced by UVB irradiation through ROS-mediated inflammation, which was related to the depletion of endogenous antioxidants, activation of MMPs and keratinocyte apoptosis. Topical treatment with all three doses of E-AP-SM2001 and 5 nm myricetin attenuated the UV-induced depletion of GSH, activation of MMPs, production of IL-1β, the decrease in IL-10 and keratinocyte apoptosis. In this study, E-AP-SM2001 showed potent inhibitory effects against UVB-induced skin photoageing. Thus, E-AP-SM2001 may be useful as a functional ingredient in cosmetics, especially as a protective agent against UVB-induced skin photoageing.

  20. Pyrrolidine dithiocarbamate inhibits UVB-induced skin inflammation and oxidative stress in hairless mice and exhibits antioxidant activity in vitro.

    PubMed

    Ivan, Ana L M; Campanini, Marcela Z; Martinez, Renata M; Ferreira, Vitor S; Steffen, Vinicius S; Vicentini, Fabiana T M C; Vilela, Fernanda M P; Martins, Frederico S; Zarpelon, Ana C; Cunha, Thiago M; Fonseca, Maria J V; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rúbia

    2014-09-05

    Ultraviolet B (UVB) irradiation may cause oxidative stress- and inflammation-dependent skin cancer and premature aging. Pyrrolidine dithiocarbamate (PDTC) is an antioxidant and inhibits nuclear factor-κB (NF-κB) activation. In the present study, the mechanisms of PDTC were investigated in cell free oxidant/antioxidant assays, in vivo UVB irradiation in hairless mice and UVB-induced NFκB activation in keratinocytes. PDTC presented the ability to scavenge 2,2'-azinobis-(3-ethyl benzothiazoline-6-sulfonic acid) radical (ABTS), 2,2-diphenyl-1-picryl-hydrazyl radical (DPPH) and hydroxyl radical (OH); and also efficiently inhibited iron-dependent and -independent lipid peroxidation as well as chelated iron. In vivo, PDTC treatment significantly decreased UVB-induced skin edema, myeloperoxidase (MPO) activity, production of the proinflammatory cytokine interleukin-1β (IL-1β), matrix metalloproteinase-9 (MMP-9), increase of reduced glutathione (GSH) levels and antioxidant capacity of the skin tested by the ferric reducing antioxidant power (FRAP) and ABTS assays. PDTC also reduced UVB-induced IκB degradation in keratinocytes. These results demonstrate that PDTC presents antioxidant and anti-inflammatory effects in vitro, which line up well with the PDTC inhibition of UVB irradiation-induced skin inflammation and oxidative stress in mice. These data suggest that treatment with PDTC may be a promising approach to reduce UVB irradiation-induced skin damages and merits further pre-clinical and clinical studies.

  1. Development of an in vivo animal model for skin penetration in hairless rats assessed by mass balance.

    PubMed

    Simonsen, Lene; Petersen, Mads B; Benfeldt, Eva; Serup, Jørgen

    2002-01-01

    The aim of the study was to develop an in vivo animal model for studies of the penetration of topically applied drugs into the skin of hairless rats. Protective appliances were designed for non-occluded and finite-dose application of topical formulations. The design allowed 2 test sites for each rat and free mobility throughout the test period. By consecutive tape stripping, monitored by measurements of transepidermal water loss and confirmed by histological examination of skin biopsies, 10 tape strippings were found to remove the stratum corneum completely. For assessment of the model, (14)C-salicylic acid and (14)C-butyl salicylate were topically applied. Rapid and differentiated percutaneous absorption of both compounds were shown by urinary excretion data. For (14)C-salicylic acid the amount on the skin surface, in the stratum corneum and in the viable skin was determined. Total mass balance on the applied radioactivity was performed and a recovery of 90 +/- 2% was achieved. The radioactivity found in the protective appliances (<10%) was explained by lateral skin diffusion of the model compounds into the dressings.

  2. Moisturizing lotions can increase transdermal absorption of the herbicide 2,4-dichlorophenoxacetic acid across hairless mouse skin.

    PubMed

    Brand, R M; Charron, A R; Sandler, V L; Jendrzejewski, J L

    2007-01-01

    Moisturizing lotions can be an effective treatment for occupationally induced dry skin. These compounds are designed to be hygroscopic and retain water to keep the stratum corneum hydrated, while at the same time enhancing the horny layer to prevent increases in transepidermal water loss (TEWL). Skin hydration levels, however, are known to influence barrier properties. The purpose of this work was to compare skin moisture levels induced by four commercially available moisturizing lotions with their capacity as transdermal penetration enhancers using the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) as a model chemical. Further, the effect of moisturizing the skin after washing with sodium lauryl sulfate (SLS) on transdermal absorption was determined. Skin moisture levels were also measured noninvasively and were correlated to penetration enhancement. Hairless mouse skin was pretreated with commercially available moisturizing lotions either with or without SLS washing and in vitro permeability studies were performed with the herbicide 2,4-D. The data demonstrate that pretreatment with three of the four lotions tested increased the transdermal absorption of 2,4-D as evidenced by cumulative penetration or faster lag times (p < 0.05). Skin moisture levels correlated with the penetration enhancement capabilities of the lotion. Washing the skin with 5% SDS increased the transdermal absorption of 2,4-D (p < 0.05) and application of moisturizing lotions increased the absorption further. In summary moisturizing lotions may influence transdermal penetration of the skin, with the more effective moisturizers having a greater effect on 2,4-D absorption.

  3. Impact of ultraviolet radiation and ozone on the transepidermal water loss as a function of skin temperature in hairless mice.

    PubMed

    Thiele, J J; Dreher, F; Maibach, H I; Packer, L

    2003-01-01

    Exposure to ultraviolet radiation or ozone leads to skin damage including oxidation of skin biomolecules, as well as to depletion of constitutive antioxidants. The highly organized stratum corneum forming the main barrier against most xenobiotics is particularly susceptible to such damage and possible barrier perturbation may be the consequence. Whereas ample evidence exists for an increased permeability for different solutes including water after exposure to ultraviolet radiation, such an effect has not yet been reported for ozone. This study reports on the effect of such oxidative stressors using the hairless mouse as the skin model and measuring temperature-controlled transepidermal water loss (TEWL) as an indicator for skin barrier integrity. First, a strong dependency of the TEWL on skin temperature was observed, an effect that was clearly more pronounced than that found in man. Given this temperature dependency in untreated animals, we proceeded to determine the effects of both ultraviolet radiation and ozone on TEWL over a relevant physiological skin temperature range. Solar-simulated ultraviolet radiation (0.75-3 minimal erythemal dose) resulted in a delayed and dose-dependent skin barrier disruption over the entire temperature range investigated. Conversely, daily ozone exposure at 2 ppm for 1 week, however, did not significantly alter TEWL up to 72 h after the last exposure. The results demonstrate a differential response of the epidermis to two environmental stressors associated with oxidative damage; they suggest that chronic ozone exposure at relevant environmental levels does not lead to a detectable skin barrier defect, while solar UV exposure was demonstrated to increase epidermal water loss. Furthermore, experimental evidence clearly suggests that future studies applying TEWL measurements in animal models should be performed under carefully controlled skin temperature conditions.

  4. Topical efficacy of dimercapto-chelating agents against lewisite-induced skin lesions in SKH-1 hairless mice

    SciTech Connect

    Mouret, Stéphane; Wartelle, Julien; Emorine, Sandy; Bertoni, Marine; Nguon, Nina; Cléry-Barraud, Cécile; Dorandeu, Frédéric; Boudry, Isabelle

    2013-10-15

    Lewisite is a potent chemical warfare arsenical vesicant that can cause severe skin lesions. Today, lewisite exposure remains possible during demilitarization of old ammunitions and as a result of deliberate use. Although its cutaneous toxicity is not fully elucidated, a specific antidote exists, the British anti-lewisite (BAL, dimercaprol) but it is not without untoward effects. Analogs of BAL, less toxic, have been developed such as meso-2,3-dimercaptosuccinic acid (DMSA) and have been employed for the treatment of heavy metal poisoning. However, efficacy of DMSA against lewisite-induced skin lesions remains to be determined in comparison with BAL. We have thus evaluated in this study the therapeutic efficacy of BAL and DMSA in two administration modes against skin lesions induced by lewisite vapor on SKH-1 hairless mice. Our data demonstrate a strong protective efficacy of topical application of dimercapto-chelating agents in contrast to a subcutaneous administration 1 h after lewisite exposure, with attenuation of wound size, necrosis and impairment of skin barrier function. The histological evaluation also confirms the efficacy of topical application by showing that treatments were effective in reversing lewisite-induced neutrophil infiltration. This protective effect was associated with an epidermal hyperplasia. However, for all the parameters studied, BAL was more effective than DMSA in reducing lewisite-induced skin injury. Together, these findings support the use of a topical form of dimercaprol-chelating agent against lewisite-induced skin lesion within the first hour after exposure to increase the therapeutic management and that BAL, despite its side-effects, should not be abandoned. - Highlights: • Topically applied dimercapto-chelating agents reduce lewisite-induced skin damage. • One topical application of BAL or DMSA is sufficient to reverse lewisite effects. • Topical BAL is more effective than DMSA to counteract lewisite-induced skin damage.

  5. Photoprotective effects of sulindac against ultraviolet B-induced phototoxicity in the skin of SKH-1 hairless mice.

    PubMed

    Athar, Mohammad; An, Kathy P; Tang, Xiuwei; Morel, Kimberly D; Kim, Arianna L; Kopelovich, Levy; Bickers, David R

    2004-03-15

    Sulindac is a nonsteroidal anti-inflammatory drug with demonstrated potency as a chemopreventive agent in animal models of carcinogenesis and in patients with familial adenomatous polyposis. Because tumor promotion is generally associated with exposure to pro-inflammatory stimuli, it is likely that anti-inflammatory agents may have potent antitumor effects. In human skin, sulindac reduces bradykinin-induced edema. In this study, we tested the hypothesis that the cyclooxygenase inhibitor sulindac can protect against ultraviolet (UVB)-induced injury that is crucial for the induction of cancer. Exposure of SKH-1 hairless mice to two consecutive doses of UVB (230 mJ/cm2) induces various inflammatory responses including erythema, edema, epidermal hyperplasia, infiltration of polymorphonuclear leukocytes, etc. Topical application of sulindac (1.25-5.0 mg/0.2 ml acetone) to the dorsal skin of SKH-1 hairless mice either 1 h before or immediately after UVB exposure substantially inhibited these inflammatory responses in a dose-dependent manner. Oral administration of sulindac in drinking water (160 ppm) for 15 days before and during UVB irradiation similarly reduced these inflammatory responses. These potent anti-inflammatory effects of sulindac suggested the possibility that the drug could inhibit signaling processes that relate to carcinogenic insult by UVB. Accordingly, studies were conducted to assess the efficacy of sulindac in attenuating the expression of UVB-induced early surrogate molecular markers of photodamage and carcinogenesis. UVB exposure enhanced the expression of p53, c-fos, cyclins D1 and A, and PCNA 24 h after irradiation. Treatment of animals with either topical or oral administration of sulindac largely abrogated the expression of these UVB-induced surrogate markers. These results indicate that the cyclooxygenase inhibitor sulindac is effective in reducing UVB-induced events relevant to carcinogenesis and that this category of topically applied or

  6. Hypochlorite solution as a decontaminant in sulfur mustard contaminated skin defects in the euthymic hairless guinea pig

    SciTech Connect

    Gold, M.B.; Bongiovanni, R.; Scharf, B.A.; Gresham, V.C.; Woodard, C.L.

    1993-05-13

    Hypochlorite solutions are thought to be efficacious when used to topically decontaminate intact skin. However, few studies have examined the efficacy of decontamination of chemically contaminated wounds. Therefore, we compared the decontamination efficacy of sodium hypochlorite (0.5% and 2.5% solutions), calcium hypochlorite (0.5% and 2.5% solutions) and sterile water to untreated controls in wounds exposed to sulfur mustard (HD). Anesthetized euthymic hairless guinea pigs (EHGP) (n=6) were exposed to 0.4 LD50 HD in a full-thickness 8 mm surgical biopsy skin defect (i.e., wound). Each animal was subsequently decontaminated, after a two-minute intra-wound exposure to liquid HD, with one of the decontamination solutions. Decontamination efficacy was determined by the visual grading of the HD-traumatized wound lesion and by comparison of the expected HD-induced leukocyte suppression. Leukocyte suppression was inconsistent in all animals; therefore, the visual grading was the only viable evaluation method. No significant differences were observed among wounds decontaminated with any of the solutions. However, the skin surrounding undecontaminated (but exposed) control animals showed the least visual pathology. The lesions induced following decontamination are presumed to be due to the mechanical flushing HD onto the peri-lesional skin, or by chemical damage induced by the solution, or HD-solution interaction. Further studies are required to best delineate the optimal decontamination process for HD contaminated wounds.

  7. Hypochlorite solution as a decontaminant in sulfur mustard contaminated skin defects in the euthymic hairless guinea pig

    SciTech Connect

    Gold, M.B.; Bongiovanni, R.; Scharf, B.A.; Gresham, V.C.; Woodward, C.L.

    1994-12-31

    Hypochlorite solutions are thought to be efficacious when used to topically decontaminate intact skin. However, few studies have examined the efficacy of decontamination of chemically contaminated wounds. Therefore, we compared the decontamination efficacy of sodium hypochlorite (0.5% and 2.5% solutions), calcium hypochlorite (0.5% and 2.5% solutions) and sterile water to untreated controls in wounds exposed to sulfur mustard (HD). Anesthetized euthymic hairless guinea pigs (EHGP) (n=6) were exposed to 20 mg/kg (approximately 0.4 LD%) HD in a full-thickness 8 mm surgical biopsy skin defect (i.e., wound). Each animal was subsequently decontaminated, after a two-minute intra-wound exposure to liquid HD, with nothing or one of the decontamination solutions. Decontamination efficacy was determined by the visual grading of the HD-traumatized wound lesion and by comparison of the expected HD-induced leukocyte suppression. Leukocyte suppression was inconsistent in all animals; therefore, the visual grading was the only viable evaluation method. No significant differences were observed among wounds decontaminated with any of the solutions. However, the skin surrounding non-decontaminated (but exposed) control animals showed the least visual pathology. The lesions induced following decontamination are presumed to be due to the mechanical flushing of HD onto the peri-lesional skin, or by chemical damage induced by the solution, or ND-solution interaction. Further studies are required to best delineate the optimal decontamination process for HD contaminated wounds.

  8. Skin permeation and distribution of two sunscreens: a comparison between reconstituted human skin and hairless rat skin.

    PubMed

    Monti, D; Brini, I; Tampucci, S; Chetoni, P; Burgalassi, S; Paganuzzi, D; Ghirardini, A

    2008-01-01

    The aims of this work were (a) to develop a simple and reproducible procedure for percutaneous absorption and distribution tests of sunscreens using one human skin culture model (Epiderm 606; reconstructed epidermis, RE), (b) to compare the said model with rat skin (RS) in vitro and (c) to evaluate the effect of different formulations. The cutaneous permeation and distribution of two UV filters, ethylhexylmethoxycinnamate (MC80) and ethylhexyltriazone (T150), using 3 different vehicles were investigated. The permeation studies demonstrated that neither MC80 nor T150 permeated through both RS and RE in spite of different thicknesses of the 2 substrates. Distribution studies demonstrated that sectioning by cryomicrotome to obtain horizontal skin layers was suitable for both RS and RE (apart from its small thickness) with a good reproducibility of data. The amounts of sunscreens retained in the 2 substrates were in the same order of magnitude for all formulations with a greater depot in RS. Different distribution profiles of the tested formulations could be ascribed to the different lipid compositions of RE and RS. Since the physicochemical characteristics of RE are closer to those of human skin, the results obtained with reconstructed human skin models could be suitable to replace human skin in 'in vitro testing'.

  9. Effect of vehicles and penetration enhancers on the in vitro percutaneous absorption of tenoxicam through hairless mouse skin.

    PubMed

    Gwak, Hye Sun; Chun, In Koo

    2002-04-02

    The effects of vehicles and penetration enhancers on the in vitro permeation of tenoxicam from saturated solutions through dorsal hairless mouse skin were investigated. Various types of vehicles, including ester-, alcohol-, and ether-types and their mixtures, were used as vehicles, and then a series of fatty acids and amines were employed as enhancers, respectively. Even though the fluxes of tenoxicam from saturated pure vehicles were generally low (0.1-1.1 microg/cm2 per h), the skin permeability of tenoxicam was significantly increased by the combination of diethylene glycol monoethyl ether (DGME) and propylene glycol monolaurate (PGML) or propylene glycol monocaprylate (PGMC); the highest fluxes were achieved at 40% of DGME in both of the two cosolvents. The marked synergistic enhancement was also obtained by using propylene glycol (PG)-oleyl alcohol (OAl) cosolvent. The greatest flux was attained by the addition of unsaturated fatty acids at 3% concentration to PG. But saturated fatty acids failed to show a significant enhancing effect. The enhancement factors with the addition of oleic acid (OA) or linoleic acid (LOA) to PG were 348 and 238, respectively. Tromethamine (TM) showed an enhancing effect by the increased solubility; however, triethanolamine (TEA) did not show a significant enhancing effect. Rather, it decreased the fluxes of tenoxicam when added to PG with fatty acids. The above results indicate that the combinations of lipophilic vehicles like OA, LOA or OAl and hydrophilic vehicles like PG can be used for enhancing the skin permeation of tenoxicam.

  10. Toxicity and penetration of TiO2 nanoparticles in hairless mice and porcine skin after subchronic dermal exposure.

    PubMed

    Wu, Jianhong; Liu, Wei; Xue, Chenbing; Zhou, Shunchang; Lan, Fengli; Bi, Lei; Xu, Huibi; Yang, Xiangliang; Zeng, Fan-Dian

    2009-12-01

    The present study investigated the penetration and potential toxicity of titanium dioxide (TiO(2)) nanoparticles following its dermal exposure in vitro and in vivo. In vitro, after exposure to isolated porcine skin for 24h, titanium dioxide nanoparticles of carious sizes cannot penetrate through stratum corneum. Interestingly, when studied in vivo, quite different results were obtained. After topically applied on pig ear for 30 days, TiO(2) nanomaterials (4 nm and 60 nm) can penetrate through horny layer, and be located in deep layer of epidermis. Furthermore, after 60 days dermal exposure in hairless mice, nano-TiO(2) particles can penetrate through the skin, reach different tissues and induce diverse pathological lesions in several major organs. Notably, P25 (21 nm) TiO(2) nanomaterials shows a wider tissue distribution, and can even be found in the brain without inducing any pathological changes. Among all of the organs examined, the skin and liver displayed the most severe pathological changes that correspond to the significant changes in SOD and MDA levels. These results suggest that the pathological lesions are likely to be mediated through the oxidative stress induced by the deposited nanoparticles. Accordingly, the collagen content expressed as HYP content are also significantly reduced in mouse skin samples, indicating that topically applied nano-TiO(2) in skin for a prolonged time can induce skin aging. Altogether, the present study indicates that nanosize TiO(2) may pose a health risk to human after dermal exposure over a relative long time period.

  11. Sex differences in skin carotenoid deposition and acute UVB-induced skin damage in SKH-1 hairless mice after consumption of tangerine tomatoes

    PubMed Central

    Kopec, Rachel E.; Schick, Jonathan; Tober, Kathleen L.; Riedl, Ken M.; Francis, David M.; Young, Gregory S.; Schwartz, Steven J.; Oberyszyn, Tatiana M.

    2015-01-01

    Scope UVB exposure, a major factor in the development of skin cancer, has differential sex effects. Tomato product consumption reduces the intensity of UVB-induced erythema in humans, but the mechanisms are unknown. Methods and results Four week old SKH-1 hairless mice (40 females, 40 males) were divided into two feeding groups (control or with 10% tangerine tomatoes naturally rich in UV-absorbing phytoene and phytofluene) and two UV exposure groups (with or without UV). After 10 weeks of feeding, the UV group was exposed to a single UV dose and sacrificed 48 hours later. Blood and dorsal skin samples were taken for carotenoid analysis. Dorsal skin was harvested to assess sex and UV effects on carotenoid deposition, inflammation (skinfold thickness, myeloperoxidase levels) and DNA damage (cyclobutane pyrimidine dimers, p53). Females had significantly higher levels of both skin and blood carotenoids relative to males. UV exposure significantly reduced skin carotenoid levels in females but not males. Tomato consumption attenuated acute UV-induced increases in CPD in both sexes, and reduced myeloperoxidase activity and % p53 positive epidermal cells in males. Conclusion Tangerine tomatoes mediate acute UV-induced skin damage in SKH-1 mice via reduced DNA damage in both sexes, and through reduced inflammation in males. PMID:26394800

  12. Protective Effect of Dermal Brimonidine Applications Against UV Radiation-induced Skin Tumors, Epidermal Hyperplasia and Cell Proliferation in the Skin of Hairless Mice.

    PubMed

    Bouvier, Guy; Learn, Douglas B; Nonne, Christelle; Feraille, Gérard; Vial, Emmanuel; Ruty, Bernard

    2015-11-01

    Brimonidine at 0.18%, 1% and 2% concentrations applied topically in hairless mice significantly decreased tumor burden and incidences of erythema, flaking, wrinkling and skin thickening induced by UVR. The unbiased median week to tumor ≥1 mm was increased by the 1% and 2% concentrations. The tumor yield was reduced by all concentrations at week 40 for all tumor sizes but the ≥4 mm tumors with the 0.18% concentration. At week 52, the tumor yield was reduced for all tumor sizes and all brimonidine concentrations. The tumor incidence was reduced by all concentrations at week 40 for all tumor sizes, but the ≥4 mm tumor with the 0.18% concentration and at week 52 for all tumor sizes with the 1% and 2% concentrations and with the 0.18% concentration only for the ≥4 mm tumors. Reductions in ≥4 mm tumor incidences compared to the vehicle control group were 54%, 91% and 86% by week 52 for the 0.18%, 1% and 2% concentrations, respectively. Brimonidine at 2% applied 1 h before or just after UVB irradiation on hairless mice decreased epidermal hyperplasia by 23% and 32% and epithelial cell proliferation by 59% and 64%, respectively, similar to an epidermal growth factor receptor (EGFR) inhibitor.

  13. A paired comparison between human skin and hairless guinea pig skin in vitro permeability and lag time measurements for 6 industrial chemicals.

    PubMed

    Frasch, H Frederick; Barbero, Ana M

    2009-01-01

    The purpose of the present study was to measure and compare permeability coefficients (k(p)) and lag times (tau) in human skin and hairless guinea pig (HGP) skin. Paired experiments employed heat-separated epidermal membranes from human and HGP sources mounted on static in vitro diffusion cells. Infinite-dose, saturated aqueous solutions of 6 industrial chemicals were used as donors: aniline, benzene, 1,2- dichloroethane, diethyl phthalate, naphthalene, and tetrachloroethylene. No significant differences were found between human and HGP skin for either k(p) or tau for any of these chemicals (p >or= .24). HGP vs. human k(p) measurements, and HGP vs. human tau measurements, were highly correlated. For k(p), the slope of the linear correlation was close to unity (1.080 +/- 0.182) and the intercept close to 0 (0.015 +/- 0. 029 cm/h), with a correlation coefficient (r(2)) = 0.898. For tau, the slope was also close to unity (0.818 +/- 0.030) and the intercept close to 0 (-0.014 +/- 0.023 h), with r(2) = 0.994. These results suggest that HGP skin may serve as an excellent surrogate for human skin in in vitro dermal penetration studies.

  14. Topical glycerol monooleate/propylene glycol formulations enhance 5-aminolevulinic acid in vitro skin delivery and in vivo protophorphyrin IX accumulation in hairless mouse skin.

    PubMed

    Steluti, Regilene; De Rosa, Fernanda Scarmato; Collett, John; Tedesco, Antônio Cláudio; Bentley, Maria Vitória Lopes Badra

    2005-08-01

    Photodynamic therapy (PDT), a potential therapy for cancer treatment, utilizes exogenously applied or endogenously formed photosensitizers, further activated by light in an appropriate wavelength and dose to induce cell death through free radical formation. 5-Aminolevulinic acid (5-ALA) is a pro-drug which can be converted to the effective photosensitizer, protoporphyrin IX (PpIX). However, the use of 5-ALA in PDT is limited by the low penetration capacity of this highly hydrophilic molecule into appropriate skin layers. In the present study, we propose to increase 5-ALA penetration by using formulations containing glycerol monooleate (GMO), an interesting and useful component of pharmaceutical formulations. Propylene glycol solutions containing different concentrations of GMO significantly increased the in vitro skin permeation/retention of 5-ALA in comparison to control solutions. In vivo studies also showed increased PpIX accumulation in mouse hairless skin, after the use of topical 5-ALA formulations containing GMO in a concentration-dependent manner. The results show that skin 5-ALA penetration and PpIX accumulation, important factors for the success of topical 5-ALA-PDT in skin cancer, are optimized by GMO/propylene glycol formulations.

  15. Protective effect of hochuekkito, a Kampo prescription, against ultraviolet B irradiation-induced skin damage in hairless mice.

    PubMed

    Yanagihara, Shigeto; Kobayashi, Hiromi; Tamiya, Hisashi; Tsuruta, Daisuke; Okano, Yuri; Takahashi, Kuniaki; Masaki, Hitoshi; Yamada, Takaaki; Hasegawa, Seiji; Akamatsu, Hirohiko; Ishii, Masamitsu

    2013-03-01

    A Kampo prescriptions, hochuekkito (HET) has been utilized for treating functional conditions such as general fatigue, compromised state and gastrointestinal motility disorder. Recently, HET has attracted the attention of dermatologists because of its clinically positive effects in atopic dermatitis (AD) treatment. To explain this positive effect of HET, we examined its protective ability against oxidative skin stress using a murine model. The dorsal region of 8-week-old male HR-1 hairless mice, which were raised on a HET (0%, 2% and 10%) mixed diet, was irradiated once with 70 mJ/cm(2) of ultraviolet (UV)-B light. After 4 days, transepidermal water loss (TEWL) and stratum corneum water content (SCWC), were determined as a measure of degree of skin dysfunction. To estimate the amount of active oxygen generated, the stratum corneum catalase activity (SCCA) and stratum corneum carbonylated protein (SCCP) content in the tape-stripped stratum corneum samples were measured. We also measured the H(2) O(2) scavenging ability of HET, and analyzed the changes in the expression levels of several inflammation and oxidative stress-related genes in the skin of HET-fed mice. In control mice, exposure to UV-B led to significant increases in TEWL and SCCP and significant decreases in SCWC and SCCA. These UV-B-induced changes were reduced in mice administrated HET, and the reduction was HET dose-dependent. Our results suggested that HET offered a protective effect against UV-B-induced skin damage. We also found that HET had relatively low ability to scavenge H(2) O(2) , and expression level of cyclooxygenase-2 mRNA decreased in HET-fed mouse.

  16. Permeation and distribution of ferulic acid and its α-cyclodextrin complex from different formulations in hairless rat skin.

    PubMed

    Monti, Daniela; Tampucci, Silvia; Chetoni, Patrizia; Burgalassi, Susi; Saino, Veronica; Centini, Marisanna; Staltari, Lucia; Anselmi, Cecilia

    2011-06-01

    Ferulic acid (FA) is a natural product that occurs in seeds of many plants where it is generally located in the bran. This compound is a multifunctional ingredient endowed with antioxidative, radical scavenging, sunscreening and antibacterial actions. The aim of this study was to analyse the ferulic acid cutaneous permeation and distribution, through and into the skin layers, from different cosmetic vehicles, an O/W emulsion (pH 6.0) and two gel-type formulations at different pH levels (6.0 and 7.4), containing FA alone or an inclusion complex with α-cyclodextrin (CD-FA). In vitro permeation studies were performed in vertical diffusion cells using hairless rat excised skin. At appropriate intervals of time, the amount of permeated sunscreen/radical scavenger was evaluated by high-performance liquid chromatography (HPLC). At the end of experiments, treated skin samples were sectioned with a cryomicrotome and the FA content of the individual slices was analysed by HPLC. FA-containing formulations, O/W emulsion, gels A and B, originated FA fluxes of 8.48 ± 2.31, 8.38 ± 0.89 and 5.72 ± 0.50 μg/cm(2) h, respectively, thus suggesting the pH influence on FA percutaneous permeation. The use of the inclusion complex, CD-FA, determined in all cases a decrease of FA transdermal permeation while no influence of pH was observed. Gel-type formulations containing FA ensured higher sunscreen storage in the superficial layers if compared with O/W emulsion. When FA was included in α-cyclodextrin, FA amount retained into skin layers decreased markedly.

  17. Effect of menthol and related terpenes on the percutaneous absorption of propranolol across excised hairless mouse skin.

    PubMed

    Kunta, J R; Goskonda, V R; Brotherton, H O; Khan, M A; Reddy, I K

    1997-12-01

    The potential use of terpenes/terpenoids as penetration enhancers in the transdermal delivery of propranolol hydrochloride (PL) was investigated. PL was chosen for the reasons of its extensive first-pass metabolism and short elimination half-life. The terpenes studied included L-menthol, (+)-limonene, (+/-)-linalool, and carvacrol at 1%, 5%, and 10% w/v concentrations. The diffusion of PL across excised hairless mouse skin was determined using side-by-side diffusion cells. Flux, permeability coefficient (Pm), and lag time (tL) were calculated. PL showed comparable lag times with menthol at all three concentration levels. At a 1% level of carvacrol, PL exhibited a 2.4- and 2.2-fold increase in lag time compared with 5 and 10% levels of enhancer, respectively. In the presence of limonene, PL had shown maximum lag time (between 3.0 and 3.3 h) at all three levels. In the case of linalool, the lag times for PL with 5 and 10% levels of enhancer were 7.0- and 5.2-fold less compared with 1% level. A significant (p < 0.05) concentration effect was observed only with linalool. Hydrogel-based patches were formulated with or without menthol as enhancer. Release profiles from the hydrogel formulations obeyed zero-order kinetics. The permeability of propranolol was significantly higher (p < 0.05) from the test patch than the control (no enhancer) patch across the mouse skin. The mechanism of permeation enhancement of menthol could involve its distribution preferentially into the intercellular spaces of stratum corneum and the possible reversible disruption of the intercellular lipid domain. The results suggest the potential use of menthol as effective penetration enhancer in the delivery of significant amounts of PL through skin.

  18. Phytosphingosine stimulates the differentiation of human keratinocytes and inhibits TPA-induced inflammatory epidermal hyperplasia in hairless mouse skin.

    PubMed

    Kim, Sujong; Hong, Il; Hwang, Jung Sun; Choi, Jin Kyu; Rho, Ho Sik; Kim, Duck Hee; Chang, Ihseop; Lee, Seung Hun; Lee, Mi-Ock; Hwang, Jae Sung

    2006-01-01

    The binding of sphingoid bases to peroxisome proliferator-activated receptor (PPAR) has been detected in a solid-phase binding assay. However, sphingoid base-induced changes in PPAR transactivation activity have not been examined. In this report, we show by reporter gene analyses that phytosphingosine (PS), a natural sphingoid base, activates the transcriptional activity of PPARs in the immortalized human keratinocyte, HaCaT. Real-time PCR analyses showed that the mRNA level of PPARgamma was increased after PS treatment in HaCaT cells in a dose- and time-dependent manner. Because PPARs play important roles in skin barrier homeostasis by regulating epidermal cell growth, terminal differentiation, and inflammatory response, we examined the effect of PS on normal human epidermal keratinocytes (NHEKs) and mouse skin. PS increased the production of cornified envelope in NHEKs by approximately 1.8-fold compared with controls. Epidermal differentiation marker proteins such as involucrin, loricrin, and keratin1 were also increased in PS-treated NHEKs, by ELISA or Western blotting analysis. A [(3)H]thymidine incorporation assay showed that PS inhibited DNA synthesis in NHEKs to 20% compared with controls. The antiproliferative and anti-inflammatory effects of PS were examined in a mouse model of irritant contact dermatitis produced by topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA). PS blocked epidermal thickening and edema and the infiltration of inflammatory cells into the dermis in the skin of TPA-treated hairless mice. The anti-inflammatory effects of PS were confirmed by the observation that PS blocked the TPA-induced generation of prostaglandin E(2) in peripheral mononuclear leukocytes. Taken together, our results provide an insight into the multiple regulatory roles of PS in epidermal homeostasis, and furthermore point to the potential use of PS as a therapeutic agent in the treatment of inflammatory and proliferative cutaneous diseases.

  19. Phytosphingosine Stimulates the Differentiation of Human Keratinocytes and Inhibits TPA-Induced Inflammatory Epidermal Hyperplasia in Hairless Mouse Skin

    PubMed Central

    Kim, Sujong; Hong, Il; Hwang, Jung Sun; Choi, Jin Kyu; Rho, Ho Sik; Kim, Duck Hee; Chang, Ihseop; Lee, Seung Hun; Lee, Mi-Ock; Hwang, Jae Sung

    2006-01-01

    The binding of sphingoid bases to peroxisome proliferator-activated receptor (PPAR) has been detected in a solid-phase binding assay. However, sphingoid base–induced changes in PPAR transactivation activity have not been examined. In this report, we show by reporter gene analyses that phytosphingosine (PS), a natural sphingoid base, activates the transcriptional activity of PPARs in the immortalized human keratinocyte, HaCaT. Real-time PCR analyses showed that the mRNA level of PPARγ was increased after PS treatment in HaCaT cells in a dose- and time-dependent manner. Because PPARs play important roles in skin barrier homeostasis by regulating epidermal cell growth, terminal differentiation, and inflammatory response, we examined the effect of PS on normal human epidermal keratinocytes (NHEKs) and mouse skin. PS increased the production of cornified envelope in NHEKs by approximately 1.8-fold compared with controls. Epidermal differentiation marker proteins such as involucrin, loricrin, and keratin1 were also increased in PS-treated NHEKs, by ELISA or Western blotting analysis. A [3H]thymidine incorporation assay showed that PS inhibited DNA synthesis in NHEKs to 20% compared with controls. The antiproliferative and anti-inflammatory effects of PS were examined in a mouse model of irritant contact dermatitis produced by topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA). PS blocked epidermal thickening and edema and the infiltration of inflammatory cells into the dermis in the skin of TPA-treated hairless mice. The anti-inflammatory effects of PS were confirmed by the observation that PS blocked the TPA-induced generation of prostaglandin E2 in peripheral mononuclear leukocytes. Taken together, our results provide an insight into the multiple regulatory roles of PS in epidermal homeostasis, and furthermore point to the potential use of PS as a therapeutic agent in the treatment of inflammatory and proliferative cutaneous diseases. PMID:16838068

  20. Effects of nociceptin and nocistatin on antidromic vasodilatation in hairless skin of the rat hindlimb in vivo.

    PubMed

    Häbler, H; Timmermann, L; Stegmann, J; Jänig, W

    1999-08-01

    1. We tested whether nociceptin (NCE), the endogenous ligand of the opioid receptor-like 1 (ORL1) receptor, and nocistatin (NST), which reverses central NCE effects when applied intrathecally (i.t.), affect small-diameter afferent fibre-mediated vasodilatation in rat hairless skin. 2. Female Wistar rats were vagotomized. Ongoing sympathetic vasoconstrictor activity was abolished by bilateral section of the lumbar sympathetic trunk between ganglia L2 and L3. Sensory axons were selectively stimulated in the dorsal root L5 by 20 electrical impulses supramaximal for activating C-fibres at 1 Hz. Blood flow was measured on the plantar skin of the left hind paw in the L5 dermatome using laser Doppler flowmetry. 3. NCE injected intravenously (i.v.) as single boluses (1, 10 and 100 nmol kg(-1) 7 - 8 min before dorsal root stimulation (n=6) dose-dependently decreased blood pressure and local vascular resistance and suppressed antidromic vasodilatation maximally by 47% (P<0.01). When NCE was injected 2 min before stimulation (n=3), antidromic vasodilatation was reduced by 64% after NCE (1 nmol kg-1) and totally, or almost totally, abolished after the two higher doses. 4. NST (1 - 100 nmol kg(-1) i.v., n=6) was without significant effect on blood pressure and cutaneous vascular resistance. Applied 5 (n=6) or 2 min (n=3) before stimulation it also did not affect antidromic vasodilatation. NST (100 nmol kg(-1) i.v.) applied shortly before an equimolar dose of NCE did not antagonize NCE effects on vascular resistance, blood pressure and antidromic vasodilatation (n=4). 5. In conclusion, NCE inhibits antidromic vasodilatation, a component of neurogenic inflammation, in rat skin while NST is without effect. NST, at the small-diameter sensory ending, is not an effective antagonist of NCE.

  1. In vitro percutaneous absorption of tenoxicam from pressure-sensitive adhesive matrices across the hairless mouse skin.

    PubMed

    Gwak, H S; Chun, I K

    2001-12-01

    To investigate the feasibility of developing a new tenoxicam plaster, the effects of vehicles and penetration enhancers on the in vitro permeation of tenoxicam from a pressure-sensitive adhesive (PSA) matrices across the dorsal hairless mouse skin were studied. Vehicles employed in this study were propylene glycol (PG)-oleyl alcohol (OAI), PG-oleic acid (OA), and diethylene glycol monoethyl ether (DGME)-propylene glycol monolaurate (PGML) cosolvents with/without fatty acids. In this study, amines such as triethanolamine (TEA) and tromethamine (TM) were additionally used as a solubilizer. Among PSAs used, Duro-Tak 87-2510 showed much higher release rate than either Duro-Tak 87-2100 or Duro-Tak 87-2196. The relatively high flux rate was obtained with the formulation of DGME-PGML (40:60, v/v) with 3% OA and 5% TM, and the flux increased as a function of the dose; the initial flux up to 12 h was 4.98 +/- 1.38 microg/cm2/h at the tenoxicam dose of 50 mg/70 cm2. This flux was much higher than that of a commercial piroxicam patch (Trast) (1.24 +/- 0.73 microg/ cm2/hr) with almost only one-third that of the commercial patch. Therefore, these observations indicated that these composition of tenoxicam plaster may be practically applicable.

  2. Oral administration of Aloe vera gel powder prevents UVB-induced decrease in skin elasticity via suppression of overexpression of MMPs in hairless mice.

    PubMed

    Saito, Marie; Tanaka, Miyuki; Misawa, Eriko; Yao, Ruiquing; Nabeshima, Kazumi; Yamauchi, Kouji; Abe, Fumiaki; Yamamoto, Yuki; Furukawa, Fukumi

    2016-07-01

    This study reports the effects of oral Aloe vera gel powder (AVGP) containing Aloe sterols on skin elasticity and the extracellular matrix in ultraviolet B (UVB)-irradiated hairless mice. Ten-week-old hairless mice were fed diets containing 0.3% AVGP for 8 weeks and irradiated UVB for 6 weeks. Mice treated with AVGP showed significant prevention of the UVB-induced decrease in skin elasticity. To investigate the mechanism underlying this suppression of skin elasticity loss, we measured the expression of matrix metalloproteinase (MMP)-2, -9, and -13. AVGP prevented both the UVB-induced increases in MMPs expressions. Moreover, we investigated hyaluronic acid (HA) content of mice dorsal skin and gene expression of HA synthase-2 (Has2). In the results, AVGP oral administration prevented UVB-induced decreasing in skin HA content and Has2 expression and attenuates the UVB-induced decrease in serum adiponectin, which promotes Has2 expression. These results suggested that AVGP has the ability to prevent the skin photoaging.

  3. Whey peptides prevent chronic ultraviolet B radiation-induced skin aging in melanin-possessing male hairless mice.

    PubMed

    Kimura, Yoshiyuki; Sumiyoshi, Maho; Kobayashi, Toshiya

    2014-01-01

    Whey proteins or peptides exhibit various actions, including an antioxidant action, an anticancer action, and a protective action against childhood asthma and atopic syndrome. The effects of orally administered whey peptides (WPs) on chronic ultraviolet B (UVB) radiation-induced cutaneous changes, including changes in cutaneous thickness, elasticity, wrinkle formation, etc., have not been examined. In this study, we studied the preventive effects of WPs on cutaneous aging induced by chronic UVB irradiation in melanin-possessing male hairless mice (HRM). UVB (36-180 mJ/cm(2)) was irradiated to the dorsal area for 17 wk in HRM, and the measurements of cutaneous thickness and elasticity in UVB irradiated mice were performed every week. WPs (200 and 400 mg/kg, twice daily) were administered orally for 17 wk. WPs inhibited the increase in cutaneous thickness, wrinkle formation, and melanin granules and the reduction in cutaneous elasticity associated with photoaging. Furthermore, it has been reported that UVB irradiation-induced skin aging is closely associated with the increase in expression of matrix metalloproteinase (MMP), vascular endothelial growth factor (VEGF), Ki-67-, and 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells. WPs also prevented increases in the expression of MMP-2 and pro-MMP-9, VEGF, and Ki-67- and 8-OHdG-positive cells induced by chronic UVB irradiation. It was found that WPs prevent type IV collagen degradation, angiogenesis, proliferation, and DNA damage caused by UVB irradiation. Overall, these results demonstrate the considerable benefit of WPs for protection against solar UV-irradiated skin aging as a supplemental nutrient.

  4. Involvement of neurokinins in antidromic vasodilatation in hairy and hairless skin of the rat hindlimb.

    PubMed

    Häbler, H J; Timmermann, L; Stegmann, J U; Jänig, W

    1999-01-01

    By intravenous application of the specific neurokininl receptor antagonist SR 140333 and the specific calcitonin gene-related peptide receptor antagonist CGRP8-37 we tested to what extent neurokinins (substance P, neurokinin A) and calcitonin gene-related peptide are involved in mediating antidromic vasodilatation in skin of anaesthetized Wistar rats. The lumbar sympathetic chain was sectioned bilaterally between ganglia L2 and L3 to remove ongoing vasoconstrictor activity to the hindquarter. The left dorsal root L5 was stimulated electrically at 1 Hz with 20 pulses supramaximal for activating C-fibres to evoke antidromic vasodilatation which was measured with laser Doppler flowmetry on the glabrous plantar skin and the hairy skin of the lower hindlimb within the left L5 territory. Stimulation-induced vasodilatation was tested after applying SR 140333 (0.1 mg/kg) and CGRP8-37 (0.3 mg/kg) alone or in combination. SR 140333 delayed the onset of the vasodilatation, but did not change its amplitude. CGRP8-37 reduced the amplitude and duration of the vasodilatation, but did not affect the latency of its onset. In combination, SR 140333 potentiated the effect of CGRP8-37 on the amplitude of the vasodilatation in glabrous but not in hairy skin and CGRP8-37 potentiated the delayed onset produced by SR 140333 in both cutaneous tissues. Antidromic vasodilatation in glabrous skin was almost totally blocked by SR 140333 (0.1 mg/kg) in combination with CGRP8-37 (0.45 mg/kg), but a substantial dilatation remained in hairy skin. It is concluded that in rat glabrous skin the vasodilatation evoked by a low level of activity in small-diameter primary afferents is likely to result from the release and synergistic action of neurokinins (substance P and/or neurokinin A) and calcitonin gene-related peptide, while in hairy skin neurokinins are involved to a minor extent only.

  5. Dietary chromium and nickel enhance UV-carcinogenesis in skin of hairless mice

    SciTech Connect

    Uddin, Ahmed N.; Burns, Fredric J.; Rossman, Toby G.; Chen, Haobin; Kluz, Thomas; Costa, Max . E-mail: costam01@nyu.edu

    2007-06-15

    The skin cancer enhancing effect of chromium (in male mice) and nickel in UVR-irradiated female Skh1 mice was investigated. The dietary vitamin E and selenomethionine were tested for prevention of chromium-enhanced skin carcinogenesis. The mice were exposed to UVR (1.0 kJ/m{sup 2} 3x weekly) for 26 weeks either alone, or combined with 2.5 or 5.0 ppm potassium chromate, or with 20, 100 or 500 ppm nickel chloride in drinking water. Vitamin E or selenomethionine was added to the lab chow for 29 weeks beginning 3 weeks before the start of UVR exposure. Both chromium and nickel significantly increased the UVR-induced skin cancer yield in mice. In male Skh1 mice, UVR alone induced 1.9 {+-} 0.4 cancers/mouse, and 2.5 or 5.0 ppm potassium chromate added to drinking water increased the yields to 5.9 {+-} 0.8 and 8.6 {+-} 0.9 cancers/mouse, respectively. In female Skh1 mice, UVR alone induced 1.7 {+-} 0.4 cancers/mouse, and the addition of 20, 100 or 500 ppm nickel chloride increased the yields to 2.8 {+-} 0.9, 5.6 {+-} 0.7 and 4.2 {+-} 1.0 cancers/mouse, respectively. Neither vitamin E nor selenomethionine reduced the cancer yield enhancement by chromium. These results confirm that chromium and nickel, while not good skin carcinogens per se, are enhancers of UVR-induced skin cancers in Skh1 mice. Data also suggest that the enhancement of UVR-induced skin cancers by chromate may not be oxidatively mediated since the antioxidant vitamin E as well as selenomethionine, found to prevent arsenite-enhanced skin carcinogenesis, failed to suppress enhancement by chromate.

  6. Cyanidin-3-Glucoside inhibits UVB-induced oxidative damage and inflammation by regulating MAP kinase and NF-κB signalling pathways in SKH-1 hairless mice skin

    PubMed Central

    Pratheeshkumar, Poyil; Son, Young-Ok; Wang, Xin; Divya, Sasidharan Padmaja; Joseph, Binoy; Hitron, John Andrew; Wang, Lei; Kim, Donghern; Yin, Yuanqin; Roy, Ram Vinod; Lu, Jian; Zhang, Zhuo; Wang, Yitao; Shi, Xianglin

    2015-01-01

    Skin cancer is one of the most commonly diagnosed cancers in the United States. Exposure to ultraviolet-B (UVB) radiation induces inflammation and photocarcinogenesis in mammalian skin. Cyanidin-3-Glucoside (C3G), a member of the anthocyanin family, is present in various vegetables and fruits especially in edible berries, and displays potent antioxidant and anticarcinogenic properties. In this study, we have assessed the in vivo effects of C3G on UVB irradiation induced chronic inflammatory responses in SKH-1 hairless mice, a well-established model for UVB-induced skin carcinogenesis. Here, we show that C3G inhibited UVB-induced skin damage and inflammation in SKH-1 hairless mice. Our results indicate that C3G inhibited glutathione depletion, lipid peroxidation and myeloperoxidation in mouse skin by chronic UVB exposure. C3G significantly decreased the production of UVB-induced pro-inflammatory cytokines, such as IL-6 and TNF-α, associated with cutaneous inflammation. Likewise, UVB-induced inflammatory responses were diminished by C3G as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases, Erk1/2, p38, JNK1/2 and MKK4. Furthermore, C3G also decreased UVB-induced cyclooxygenase-2 (COX-2), PGE2 and iNOS levels, which are well-known key mediators of inflammation and cancer. Treatment with C3G inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in mice skin. Immunofluorescence assay revealed that topical application of C3G inhibited the expression of 8-hydroxy-2′-deoxyguanosine, proliferating cell nuclear antigen, and cyclin D1 in chronic UVB exposed mouse skin. Collectively, these data indicates that C3G can provide substantial protection against the adverse effects of UVB radiation by modulating UVB-induced MAP kinase and NF-κB signaling pathways. PMID:25062774

  7. Histomorphological and angiogenic analyzes of skin epithelium after low laser irradiation in hairless mice.

    PubMed

    Leão, Juliane Caroline; Issa, João Paulo Mardegan; Pitol, Dimitrius Leonardo; Rizzi, Ellen Camargo; Dias, Fernando José; Siéssere, Selma; Regalo, Simone Cecílio Hallak; Iyomasa, Mamie Mizusaki

    2011-09-01

    It is not well-understood how low-laser therapy affects the skin of the applied area. This study analyzes skin of the masseteric region of mice from the HRS/J strain after three different application regimens (three, six or ten applications per regimen) of low intensity laser at 20 J/cm(2) and 40 mW for 20 sec on alternate days. Three experimental groups according to the number of laser applications (three, six or ten) and three control groups (N = 5 animals for each group) were used. On the third day after the last irradiation, all animals were sacrificed and the skin was removed and processed to analyze the relative occupation of the test area by each epithelial layer and the aspects of neovascularization. Data were submitted to statistical analyzes. The irradiated groups compared to their respective controls at each period of time, showed no significant difference in relative occupation of the test area by the layers and epithelium areas for three and six applications, but for ten applications, a significant decrease (P < 0.05) in the basal and granulosum layers, and epithelium areas were found. From the comparisons of the three irradiated groups together, the group with six laser applications showed statistical difference (P < 0.05) in total epithelium and on the layers. Vascular endothelial growth factor (VEGF) and VEGFR-2 immunoreactivities were similar for the control and irradiated groups. Results suggested a biostimulatory effect with low risks associated with superficial tissues, when the treatment aims the deeper layers after six applications.

  8. Effects of a turmeric extract (Curcuma longa) on chronic ultraviolet B irradiation-induced skin damage in melanin-possessing hairless mice.

    PubMed

    Sumiyoshi, Maho; Kimura, Yoshiyuki

    2009-12-01

    Turmeric (the rhizomes of Curcuma longa L., Zingiberacease) is widely used as a dietary pigment and spice, and has been traditionally used for the treatment of inflammation, skin wounds and hepatic disorders in Ayurvedic, Unani and Chinese medicine. Although the topical application or oral administration of turmeric is used to improve skin trouble, there is no evidence to support this effect. The aim of this study was to clarify whether turmeric prevents chronic ultraviolet B (UVB)-irradiated skin damage. We examined the effects of a turmeric extract on skin damage including changes in skin thickness and elasticity, pigmentation and wrinkling caused by long-term, low-dose ultraviolet B irradiation in melanin-possessing hairless mice. The extract (at 300 or 1000 mg/kg, twice daily) prevented an increase in skin thickness and a reduction in skin elasticity induced by chronic UVB exposure. It also prevented the formation of wrinkles and melanin (at 1000 mg/kg, twice daily) as well as increases in the diameter and length of skin blood vessels and in the expression of matrix metalloproteinase-2 (MMP-2). Prevention of UVB-induced skin aging by turmeric may be due to the inhibition of increases in MMP-2 expression caused by chronic irradiation.

  9. Dose-response on the chemopreventive effects of sarcophine-diol on UVB-induced skin tumor development in SKH-1 hairless mice.

    PubMed

    Guillermo, Ruth F; Zhang, Xiaoying; Kaushik, Radhey S; Zeman, David; Ahmed, Safwat A; Khalifa, Sherief; Fahmy, Hesham; Dwivedi, Chandradhar

    2012-09-01

    Sarcophine-diol (SD) is a lactone ring-opened analogue of sarcophine. It has shown chemopreventive effects on chemically-induced skin tumor development in female CD-1 mice, as well as in a UVB-induced skin tumor development model in hairless SKH-1 mice at a dose of 30 μg SD applied topically and 180 mJ/cm(2) UVB. The objective of this study was to determine the dose-response on the chemopreventive effects of SD on SKH-1 hairless mice when exposed to a UVB radiation dose of 30 mJ/cm(2). This UVB dose better represents chronic human skin exposure to sunlight leading to skin cancer than previous studies applying much higher UVB doses. Carcinogenesis was initiated and promoted by UVB radiation. Female hairless SKH-1 mice were divided into five groups. The control group was topically treated with 200 μL of acetone (vehicle), and the SD treatment groups were topically treated with SD (30 μg, 45 μg, and 60 μg dissolved in 200 μL of acetone) 1 h before UVB radiation (30 mJ/cm(2)). The last group of animals received 60 μg SD/200 μL acetone without UVB exposure. These treatments were continued for 27 weeks. Tumor multiplicity and tumor volumes were recorded on a weekly basis for 27 weeks. Weight gain and any signs of toxicity were also closely monitored. Histological characteristics and the proliferating cell nuclear antigen (PCNA) were evaluated in the mice skin collected at the end of the experiment. The dose-response study proved a modest increase in chemopreventive effects with the increase in SD dose. SD reduced the number of cells positively stained with PCNA proliferation marker in mice skin. The study also showed that SD application without UVB exposure has no effect on the structure of skin. The results from this study suggest that broader range doses of SD are necessary to improve the chemopreventive effects.

  10. Protective Effect of Inositol Hexaphosphate Against UVB Damage in HaCaT Cells and Skin Carcinogenesis in SKH1 Hairless Mice

    PubMed Central

    Williams, Kendra A; Kolappaswamy, Krishnan; DeTolla, Louis J; Vucenik, Ivana

    2011-01-01

    UVB radiation damages keratinocytes, potentially inducing chronic skin damage, cutaneous malignancy, and suppression of the immune system. Naturally occurring agents have been considered for prevention and treatment of various kinds of cancer, including skin cancer. Inositol hexaphosphate (IP6), an antioxidant, is a naturally occurring polyphosphorylated carbohydrate that has shown a strong anticancer activity in several experimental models. We assessed the protective effects of IP6 against UVB irradiation-induced injury and photocarcinogenesis by using HaCaT cells (human immortalized keratinocytes) and SKH1 hairless mice. We found that IP6 counteracts the harmful effects of UVB irradiation and increases the viability and survival of UVB-exposed cells. Treatment with IP6 after UVB irradiation (30 mJ/cm2) arrested cells in the G1 and G2M phases while decreasing the S phase of the cell cycle. Treatment with IP6 also decreased UVB-induced apoptosis and caspase 3 activation. Topical application of IP6 followed by exposure to UVB irradiation in SKH1 hairless mice decreased tumor incidence and multiplicity as compared with control mice. Our results suggest that IP6 protects HaCaT cells from UVB-induced apoptosis and mice from UVB-induced tumors. PMID:21819680

  11. Dietary, but not topical, alpha-linolenic acid suppresses UVB-induced skin injury in hairless mice when compared with linoleic acids.

    PubMed

    Takemura, Naoya; Takahashi, Kazuhiko; Tanaka, Hiroshi; Ihara, Yuka; Ikemoto, Atsushi; Fujii, Yoichi; Okuyama, Harumi

    2002-12-01

    Peroxidizability of fatty acids in the air is roughly proportional to the number of double bonds, but in vivo peroxidation proceeds in a more complex manner. Here, we compared the effects of dietary and topically applied oils enriched with linoleic acid (LA, 18:2n-6) or alpha-linolenic acid (ALA, 18:3n-3) on UV-induced skin injury in a strain of hairless mice. The UVB-induced erythema score was significantly lower in mice with topically applied creams containing LA and ALA than in mice with the basal cream; no significant increase in the score was detected in the ALA group compared with the LA group. However, dietary ALA inhibited the increase in erythema score after UVB irradiation compared with LA. The peroxidizability index of the skin total lipids was significantly higher, but UVB-induced prostaglandin E2 (PGE2) production was significantly lower in the group fed an ALA-rich diet compared with the group fed an LA-rich diet. The levels of thiobarbituric acid-reactive substances, estimated in the presence of butylated hydroxytoluene in the assay mixture, were not affected by UVB treatment or by the dietary fatty acids, but the severity of the skin lesion was associated with PGE2 levels. These results indicate that the type of fatty acids, n-6 or n-3, is critical for the suppression of UVB-induced skin lesion when the skin fatty acids are modified by dietary manipulation. Anti-inflammatory activity of dietary flaxseed oil with relatively high ALA and low LA contents was demonstrated in UVB-irradiated hairless mice.

  12. Inhibitory effect of glycolic acid on ultraviolet-induced skin tumorigenesis in SKH-1 hairless mice and its mechanism of action.

    PubMed

    Hong, J T; Kim, E J; Ahn, K S; Jung, K M; Yun, Y P; Park, Y K; Lee, S H

    2001-07-01

    Glycolic acid, an alpha-hydroxy acid derived from fruit and milk sugars, has been used commonly as a cosmetic ingredient since it was discovered to have photoprotective and anti-inflammatory effects and antioxidant effects on ultraviolet (UV)B-irradiated skin. Little is known, however, about the functional role of glycolic acid on UV-induced skin tumorigenesis. In the present study, we examined the effect of glycolic acid on UV (UVA + UVB)-induced skin tumorigenesis and assessed several significant contributing factors in SKH-1 hairless mice. Inbred hairless female mice (15 animals/group) were irradiated for 5 d/wk at a total dose of 74.85 J/cm(2) UVA and 2.44 J/cm(2) UVB for 22 wk. Glycolic acid was applied topically twice a week at a dose of 8 mg/cm(2) immediately after UV irradiation. Glycolic acid reduced UV-induced skin tumor development. The protective effect of glycolic acid was a 20% reduction of skin tumor incidence, a 55% reduction of tumor multiplicity (average number of tumors/mouse), and a 47% decrease in the number of large tumors (larger than 2 mm). Glycolic acid also delayed the first appearance of tumor formation by about 3 wk. The inhibitory effect of glycolic acid on UV-induced tumor development was accompanied by decreased expression of the following UV-induced cell-cycle regulatory proteins: proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin E, and the associated subunits cyclin-dependent kinase 2 (cdk2) and cdk4. In addition, the expression of p38 kinase, jun N-terminal kinase (JNK), and mitogen-activated protein kinase kinase (MEK) also was lower in UV + glycolic acid-treated skin compared with expression in UV-irradiated skin. Moreover, transcription factors activator protein 1 (AP-1) and nuclear factor kappaB (NF-kappaB) activation was significantly lower in UV + glycolic acid-treated skin compared with activation in UV-irradiated skin. These results show that glycolic acid reduced UV-induced skin tumor development. The decreased

  13. French maritime pine bark (Pinus maritima Lam.) extract (Flavangenol) prevents chronic UVB radiation-induced skin damage and carcinogenesis in melanin-possessing hairless mice.

    PubMed

    Kimura, Yoshiyuki; Sumiyoshi, Maho

    2010-01-01

    A French maritime pine bark extract, Flavangenol, is widely used as a nutritional supplement for protection against atherosclerosis, hypertension, diabetes, etc. Chronic exposure to solar UV radiation damages skin, increasing cutaneous thickness, wrinkling and pigmentation, as well as reducing elasticity, and causes skin cancer. The aim of this study was to examine the effects of flavangenol on skin damage and the incidence of skin tumors caused by long-term UVB irradiation in melanin-possessing hairless mice. The oral administration of flavangenol (60, 200 or 600 mg kg(-1), twice daily) significantly inhibited increases in skin thickness, and the formation of wrinkles and melanin granules, as well as increases in the diameter and length of skin blood vessels. Furthermore, it prevented increases in numbers of apoptotic, Ki-67-positive and 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells, and the expression of skin vascular endothelial growth factor (VEGF) induced by chronic UVB irradiation. The effect on these biomarkers was associated with a reduction in the incidence of tumors in mice. The antiphotoaging and anticarcinogenetic activities of flavangenol may be due to inhibition of the expression of Ki-67, 8-OHdG and VEGF through a scavenging effect on reactive oxygen species.

  14. The effect of local UVB skin irradiation on the rate of formazan deposition in the epidermis of hairless mice studied by means of a tetrazolium-reduction method.

    PubMed

    Fosså, J; Iversen, O H; Thune, P O

    1980-01-01

    One-hundred-and-twenty hairless mice were irradiated with UVB (310 nm, exposure 60 mJ/cm2) on a limited area of the dorsal skin. At different time intervals after irradiation, the rate of endogenous dehydrogenase activity per mg dry epidermis was measured by the tetrazolium reduction method. The amount of formazan deposited remained normal for 18 h, and then increased, reaching a peak significantly higher than normal at 24 h, and thereafter returned to normal. At day 8 there was a new, probably significant peak. The reaction was followed for 14 days. It was concluded that UVB irradiation provokes a period of increased formazan deposition in the epidermis, similar to what has been observed after ionizing radiation and chemical carcinogens. The validity of the tetrazolium test for skin carcinogenic irritaments was thus also confirmed.

  15. Cutaneous challenge with chemical warfare agents in the SKH-1 hairless mouse. (I) Development of a model for screening studies in skin decontamination and protection.

    PubMed

    Dorandeu, F; Taysse, L; Boudry, I; Foquin, A; Hérodin, F; Mathieu, J; Daulon, S; Cruz, C; Lallement, G

    2011-06-01

    Exposure to lethal chemical warfare agents (CWAs) is no longer only a military issue due to the terrorist threat. Among the CWAs of concern are the organophosphorus nerve agent O-ethyl-S-(2[di-isopropylamino]ethyl)methyl-phosphonothioate (VX) and the vesicant sulfur mustard (SM). Although efficient means of decontamination are available, most of them lose their efficacy when decontamination is delayed after exposure of the bare skin. Alternatively, CWA skin penetration can be prevented by topical skin protectants. Active research in skin protection and decontamination is thus paramount. In vivo screening of decontaminants or skin protectants is usually time consuming and may be expensive depending on the animal species used. We were thus looking for a suitable, scientifically sound and cost-effective model, which is easy to handle. The euthymic hairless mouse Crl: SKH-1 (hr/hr) BR is widely used in some skin studies and has previously been described to be suitable for some experiments involving SM or SM analogs. To evaluate the response of this species, we studied the consequences of exposing male anaesthetized SKH-1 mice to either liquid VX or to SM, the latter being used in liquid form or as saturated vapours. Long-term effects of SM burn were also evaluated. The model was then used in the companion paper (Taysse et al.(1)).

  16. Cyanidin-3-glucoside inhibits UVB-induced oxidative damage and inflammation by regulating MAP kinase and NF-κB signaling pathways in SKH-1 hairless mice skin

    SciTech Connect

    Pratheeshkumar, Poyil; Son, Young-Ok; Wang, Xin; Divya, Sasidharan Padmaja; Joseph, Binoy; Hitron, John Andrew; Wang, Lei; Kim, Donghern; Yin, Yuanqin; Roy, Ram Vinod; Lu, Jian; Zhang, Zhuo; Wang, Yitao; and others

    2014-10-01

    Skin cancer is one of the most commonly diagnosed cancers in the United States. Exposure to ultraviolet-B (UVB) radiation induces inflammation and photocarcinogenesis in mammalian skin. Cyanidin-3-glucoside (C3G), a member of the anthocyanin family, is present in various vegetables and fruits especially in edible berries, and displays potent antioxidant and anticarcinogenic properties. In this study, we have assessed the in vivo effects of C3G on UVB irradiation induced chronic inflammatory responses in SKH-1 hairless mice, a well-established model for UVB-induced skin carcinogenesis. Here, we show that C3G inhibited UVB-induced skin damage and inflammation in SKH-1 hairless mice. Our results indicate that C3G inhibited glutathione depletion, lipid peroxidation and myeloperoxidation in mouse skin by chronic UVB exposure. C3G significantly decreased the production of UVB-induced pro-inflammatory cytokines, such as IL-6 and TNF-α, associated with cutaneous inflammation. Likewise, UVB-induced inflammatory responses were diminished by C3G as observed by a remarkable reduction in the levels of phosphorylated MAP kinases, Erk1/2, p38, JNK1/2 and MKK4. Furthermore, C3G also decreased UVB-induced cyclooxygenase-2 (COX-2), PGE{sub 2} and iNOS levels, which are well-known key mediators of inflammation and cancer. Treatment with C3G inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in mice skin. Immunofluorescence assay revealed that topical application of C3G inhibited the expression of 8-hydroxy-2′-deoxyguanosine, proliferating cell nuclear antigen, and cyclin D1 in chronic UVB exposed mouse skin. Collectively, these data indicates that C3G can provide substantial protection against the adverse effects of UVB radiation by modulating UVB-induced MAP kinase and NF-κB signaling pathways. - Highlights: • C3G inhibited UVB-induced oxidative damage and inflammation. • C3G inhibited UVB-induced COX-2, iNOS and PGE{sub 2} production. • C3G

  17. A Medical Research and Evaluation Facility and Studies Supporting the Medical Chemical Defense Program. Task 92-29: Efficacy Assessment of Topical Skin Protectants against Sulfur Mustard Vapors in Hairless Guinea Pigs.

    DTIC Science & Technology

    1997-09-01

    hairless guinea pigs ( HGPs ) and the incidence of microblisters observed histologically. The dose-response curve was compared to results of similar work...performed at the U.S. Army Medical Research Institute of Chemical Defense (USAMRICD). The effects of ketamine hydrochloride anesthesia on HGP skin...reflectance were also examined. The exposure time needed to produce a 50 percent incidence of microblisters in HGP skin exposed to saturated HD vapors was

  18. Peroxidized cholesterol-induced matrix metalloproteinase-9 activation and its suppression by dietary beta-carotene in photoaging of hairless mouse skin.

    PubMed

    Minami, Yuko; Kawabata, Kyuichi; Kubo, Yoshiaki; Arase, Seiji; Hirasaka, Katsuya; Nikawa, Takeshi; Bando, Noriko; Kawai, Yoshichika; Terao, Junji

    2009-05-01

    The activation of matrix metalloproteinase (MMP)-9 leading to the formation of wrinkle and sagging of skin is an essential step in the skin photoaging on exposure to ultraviolet A (UVA). This study attempted to elucidate the role of peroxidized cholesterol including cholesterol hydroperoxides (Chol-OOHs), primary products of lipid peroxidation in biomembranes, in MMP-9 activation and the effect of dietary beta-carotene in MMP-9 activation. Hairless mice were subjected to periodic UVA irradiation for 8 weeks. The amount of peroxidized cholesterol detected as total hydroxycholesterol in the skin was increased significantly by the exposure. The activity and protein level of MMP-9 were elevated with wrinkling and sagging formation. MMP-9 activity was also enhanced by the intracutaneous injection of Chol-OOHs into the mouse skin. Adding beta-carotene to the diet of the mice during the period of irradiation suppressed the activity and expression of MMP-9 as well as the wrinkling and sagging formation. The amount of cholesterol 5alpha-hydroperoxide, a singlet molecular oxygen oxygenation-specific peroxidized cholesterol, was significantly lowered by the addition of beta-carotene to the diet. These results strongly suggest that Chol-OOHs formed on exposure to UVA contribute to the expression of MMP-9, resulting in photoaging. Dietary beta-carotene prevents the expression of MMP-9, at least partly, by inhibiting photodynamic action involved in the formation of Chol-OOHs.

  19. Clinically-Relevant Cutaneous Lesions by Nitrogen Mustard: Useful Biomarkers of Vesicants Skin Injury in SKH-1 Hairless and C57BL/6 Mice

    PubMed Central

    Tewari-Singh, Neera; Jain, Anil K.; Inturi, Swetha; White, Carl W.; Agarwal, Rajesh

    2013-01-01

    A paucity of clinically applicable biomarkers to screen therapies in laboratory is a limitation in the development of countermeasures against cutaneous injuries by chemical weapon, sulfur mustard (SM), and its analog nitrogen mustard (NM). Consequently, we assessed NM-caused progression of clinical cutaneous lesions; notably, skin injury with NM is comparable to SM. Exposure of SKH-1 hairless and C57BL/6 (haired) mice to NM (3.2 mg) for 12–120 h caused clinical sequelae of toxicity, including microblister formation, edema, erythema, altered pigmentation, wounding, xerosis and scaly dry skin. These toxic effects of NM were similar in both mouse strains, except that wounding and altered pigmentation at 12–24 h and appearance of dry skin at 24 and 72 h post-NM exposure were more pronounced in C57BL/6 compared to SKH-1 mice. Conversely, edema, erythema and microblister formation were more prominent in SKH-1 than C57BL/6 mice at 24–72 h after NM exposure. In addition, 40–60% mortality was observed following 120 h of NM exposure in the both mouse strains. Overall, these toxic effects of NM are comparable to those reported in humans and other animal species with SM, and thus represent clinically-relevant cutaneous injury endpoints in screening and optimization of therapies for skin injuries by vesicating agents. PMID:23826320

  20. Oral administration of Polypodium leucotomos delays skin tumor development and increases epidermal p53 expression and the anti-oxidant status of UV-irradiated hairless mice.

    PubMed

    Rodríguez-Yanes, Esperanza; Cuevas, Jesús; González, Salvador; Mallol, Jordi

    2014-07-01

    Chronic exposure to ultraviolet radiation (UVR) induces skin tumors in hairless mice. Daily oral administration of a Polypodium leucotomos (PL) extract significantly delayed tumor development in PL-treated versus non-PL-treated mice. UVR and/or PL treatment modified several oxidative stress markers. In all irradiated mice, erythrocytic glutathione S-transferase (GST) activity and glutathione disulphide (GSSG) content increased and in all PL-treated mice GSSG content decreased, specially in non-irradiated animals, and total plasma anti-oxidant capacity (ORAC) increased. In dorsolateral non-tumoral skin of all irradiated mice, glutathione reductase (GR) and glutathione peroxidase (GPx) activities increased and GSSG decreased in non-irradiated PL-treated animals. UVR induced a steep increase of p53 expression in epidermal cells. In non-tumoral skin, this increase was significantly higher in PL-treated animals than in non-treated mice and can contribute in delaying tumor development, either by repairing the damaged DNA or by increasing apoptosis. These results reinforce the usefulness of PL as systemic photoprotective agent, especially in patients highly sensitive to UVR.

  1. Intake of high-fat diet stimulates the risk of ultraviolet radiation-induced skin tumors and malignant progression of papillomas to carcinoma in SKH-1 hairless mice

    SciTech Connect

    Vaid, Mudit; Singh, Tripti; Prasad, Ram; Katiyar, Santosh K.

    2014-01-01

    Previously, we showed that administration of a high-fat diet (HF-diet) to C57BL/6 mice exacerbates their response to short-term UVB radiation-induced inflammation in the skin. To explore the effects of an HF-diet on UVB-induced tumorigenesis, we have used the SKH-1 hairless mouse model in which the mice are exposed to UVB radiation (180 mJ/cm{sup 2}) three times a week for 24 weeks. The development of UVB-induced skin tumors was rapid and the tumor multiplicity and tumor size were significantly higher (P < 0.01–0.005) in the mice fed an HF-diet than the mice fed a control-diet (C-diet). Moreover, the malignant progression of UVB-induced papillomas to carcinomas was higher in HF-diet-fed mice. On analysis of tumors and tumor-uninvolved skin samples from the tumor-bearing mice, we found that administration of an HF-diet significantly enhanced the levels of UVB-induced expression of cyclooxygenase-2 (COX-2), prostaglandin E{sub 2} (P < 0.01), and PGE{sub 2} receptors, and activation of NF-κB in the UVB-exposed skin as well as in tumors. In addition the HF-diet enhanced the expression of proinflammatory cytokines, including tumor necrosis factor-α (P < 0.01), interleukin (IL)-1β (P < 0.01) and IL-6 (P < 0.05) in the UVB-exposed skin as well as in tumors. Western blot analysis revealed that HF-diet enhanced the levels of epidermal cell proliferation, phosphatidylinositol 3-kinase and phosphorylation of Akt at Ser{sup 473} in UVB-exposed skin and skin tumors. Collectively, these data demonstrate that the regular consumption of an HF-diet increases the risk of photocarcinogenesis in mice and that this is associated with enhanced expression of inflammatory mediators in the UVB-exposed skin and tumors. - Highlights: • Consumption of high-fat diet increases UVB-induced skin tumor development in mice. • Intake of high-fat diet stimulates progression of UV-induced papilloma to carcinoma. • Intake of high-fat diet enhances inflammation in UV-exposed skin • Regular

  2. Studies of in vitro skin permeation and retention of a leukotriene antagonist from topical vehicles with a hairless guinea pig model.

    PubMed

    Kumar, S; Malick, A W; Meltzer, N M; Mouskountakis, J D; Behl, C R

    1992-07-01

    A leukotriene antagonist [Ro 23-3544; 6-acetyl-7-[5-(4-acetyl-3-hydroxy-2-propylphenoxy)pentyloxy] -3,4-dihydro-2H-1-benzopyran-2-carboxylic acid; 1] was studied in vitro for its permeation through and retention in hairless guinea pig skin from various topical vehicles. Both the free acid and the sodium salt forms of the drug were used. The vehicles evaluated were polyethylene glycol 400, propylene glycol, dimethyl sulfoxide (DMSO), C12-C15 alcohol lactates, dimethyl isosorbide, butyrolactone, methylpyrrolidone, hexyl laurate, isopropyl myristate, and caprylic/capric triglyceride (Neobee M5). For the salt form of the drug, the highest permeability coefficient and retention were obtained from DMSO and methylpyrrolidone, respectively. For the acid form, however, the highest permeability coefficient and retention were obtained from hexyl laurate and DMSO, respectively. The highest permeation and retention values were not obtained from the same vehicle for either the salt or the acid form of the drug. This observation questions the validity of using permeation (flux) measurements to screen topical drugs and formulations. Although the precise reasons for this lack of correlation between permeation and retention are not known at this time, this study has shown that the solubility parameters of the drug and the vehicles used may play an important role. It seems logical to conduct skin retention studies rather than flux measurements in evaluating drug delivery from dermatological products.

  3. In vitro and in vivo comparison of dermal irritancy of jet fuel exposure using EpiDerm (EPI-200) cultured human skin and hairless rats.

    PubMed

    Chatterjee, Abhijit; Babu, R Jayachandra; Klausner, M; Singh, Mandip

    2006-12-01

    The purpose of this study was to evaluate an in vitro EpiDerm human skin model (EPI-200) to study the irritation potential of jet fuels (JP-8 and JP-8+100). Parallel in vivo studies on hairless rats on the dermal irritancy of jet fuels were also conducted. Cytokines are an important part of an irritation and inflammatory cascade, which are expressed in upon dermal exposures of irritant chemicals even when there are no obvious visible marks of irritation on the skin. We have chosen two primary cytokines (IL-1alpha and TNF-1alpha) as markers of irritation response of jet fuels. Initially, the EPI-200 was treated with different quantities of JP-8 and JP-8+100 to determine quantities which did not cause significant cytotoxicity, as monitored using the MTT assay and paraffin embedded histological cross-sections. Volumes of 2.5-50 microl/tissue (approximately 4.0-78 microl/cm2) of JP-8 and JP-8+100 showed a dose dependent loss of tissue viability and morphological alterations of the tissue. At a quantity of 1.25 microl/tissue (approximately 2.0 microl/cm2), no significant change in tissue viability or morphology was observed for exposure time extending to 48 h. Nonetheless, this dose induced significant increase in IL-1alpha and TNF-alpha release versus non-treated controls after 24 and 48 h. In addition, IL-1alpha release for JP-8+100 was significantly higher than that observed for JP-8, but TNF-alpha release after 48 h exposure to these two jet fuels was the same. These findings parallel in vivo studies on hairless rats, which indicated higher irritation levels due to JP-8+100 versus JP-8. In vivo, transepidermal water loss (TEWL) and IL-1alpha expression levels followed the order JP-8+100 > JP-8 > control. Further, in vivo TNF-alpha levels for JP-8 and JP-8+100 were also elevated but not significantly different from one another. In aggregate, these findings indicate that EPI-200 tissue model can be utilized as an alternative to the use of animals in evaluating dermal

  4. Daily Ingestion of Aloe Vera Gel Powder Containing Aloe Sterols Prevents Skin Photoaging in OVX Hairless Mice.

    PubMed

    Yao, Ruiqing; Tanaka, Miyuki; Misawa, Eriko; Saito, Marie; Nabeshima, Kazumi; Yamauchi, Koji; Abe, Fumiaki; Yamamoto, Yuki; Furukawa, Fukumi

    2016-10-12

    Estrogen deficiencies associated with menopause accelerate spontaneous skin aging and stimulate the ultraviolet (UV) irradiation-induced photoaging of skin. However, food compositions with the potential to ameliorate the UV irradiation-induced acceleration of skin aging with menopause have not yet been investigated in detail. In the present study, we examined the ability of plant sterols derived from Aloe vera gel to prevent the UV irradiation-induced acceleration of skin aging in ovariectomized mice. Skin transepidermal water loss (TEWL) was significantly higher in the ovariectomy group than in the sham operation group following UVB irradiation, whereas skin elasticity was significantly lower. Ultraviolet B (UVB) irradiation induced greater reductions in skin hyaluronic acid levels and more severe collagen fiber damage in the derims in the ovariectomy group than in the sham group. The intake of AVGP significantly ameliorated this acceleration in skin aging by reducing the expression of matrix metalloproteinases (MMPs) and increasing that of epidermal growth factor (EGF) and hyaluronan synthase (HAS) in the skin. These results indicate that AVGP supplementation prevents skin damage induced by UVB irradiation and ovariectomy in part by inhibiting damage to the extracellular matrix.

  5. Fractionation of a tumor-initiating UV dose introduces DNA damage-retaining cells in hairless mouse skin and renders subsequent TPA-promoted tumors non-regressing

    PubMed Central

    van de Glind, Gerline; Rebel, Heggert; van Kempen, Marika; Tensen, Kees; de Gruijl, Frank

    2016-01-01

    Sunburns and especially sub-sunburn chronic UV exposure are associated with increased risk of squamous cell carcinomas (SCCs). Here we focus on a possible difference in tumor initiation from a single severe-sunburn dose (on day 1, 21 hairless mice) and from an equal dose fractionated into very low sub-sunburn doses not causing any (growth-promoting) epidermal hyperplasia (40 days daily exposure, n=20). From day 47 all mice received 12-O-Tetradecanoylphorbol-13-acetate (TPA) applications (2x/wk) for 20 weeks to promote tumor development within the lifetime of the animals. After the sub-sunburn regimen sparse DNA damage-retaining basal cells (quiescent stem cells, QSCs) remained in the non-hyperplastic epidermis. These cells were forced to divide by TPA. After discontinuation of TPA tumors regressed and disappeared in the ‘sunburn group’ but persisted and grew in the ‘sub-sunburn group’ (0.06 vs 2.50 SCCs and precursors ≥4mm/mouse after 280 days, p=0.03). As the tumors carried no mutations in p53, H/K/N-Ras and Notch1/2, these ‘usual suspects' were not involved in the UV-driven tumor initiation. Although we could not selectively eliminate QSCs (unknown phenotype) to establish causality, our data suggest that forcing specifically DNA damage-retaining QSCs to divide – with high mutagenic risk - gives rise to persisting (mainly ‘in situ’) skin carcinomas. PMID:26797757

  6. Intraepidermal free nerve fiber endings in the hairless skin of the rat as revealed by the zinc iodide-osmium tetroxide technique.

    PubMed

    Müller, T

    2000-04-01

    The nerve fiber distribution in the epidermis of the hairless rat skin was studied light microscopically by means of zinc iodide-osmium tetroxide staining. Two different morphological types of free nerve fiber endings could be detected: clusters of relatively thick nerve fibers stretched up through the spinous layer up to the granular layer sending off terminal branches. In addition, many solitary thin varicose nerve fibers were seen within the epidermis. The observed discrepancies in nerve fiber diameters appeared to be larger than those reported for human intraepidermal nerve fibers in recent immunohistochemical studies. Moreover, dendritic cells, most probably representing Langerhans cells, could be selectively stained. These cells appeared to be in a close location to thin varicose nerve fibers. Both types of demonstrated free nerve endings have to be functionally connected with different sensoric functions. Possibly, a subpopulation of the thin nerve fibers might possess primarily a nociceptive task, whereas the thick ones have most probably to be regarded as mechanoreceptive. The nerve fibers innervating dendritic cells appear to be identical to the peptidergic ones which may regulate the antigen-presenting capacity of these cells. Due to its selectivity for intraepidermal nerve fibers, the used method might supplement immunohistochemical procedures in a helpful manner.

  7. Protective effects of the antioxidant extract collected from Styela clava tunics on UV radiation‑induced skin aging in hairless mice.

    PubMed

    Koh, Eun Kyoung; Kim, Ji Eun; Go, Jun; Song, Sung Hwa; Sung, Ji Eun; Son, Hong Joo; Jung, Young Jin; Kim, Bae Hwan; Jung, Young Suk; Hwang, Dae Youn

    2016-11-01

    Ultraviolet (UV) radiation is considered a primary cause of skin damage, which is characterized by deep wrinkles, roughness, laxity and pigmentation through oxidative stress and oxidative photodamage. To examine the therapeutic effects of ethanol extract of Styela clava tunics (EtSCT) on UV radiation-induced skin aging in hairless mice, alterations in skin phenotype, histological structures, inflammation, endoplasmic reticulum (ER) stress, oxidative conditions and toxicity were investigated during 13 weeks of UV irradiation and topical application of EtSCT. EtSCT showed high reducing power (3.1%), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (92.7%) and NO scavenging activity (15.6%) due to its high total flavonoids (15.3 mg/ml) and total phenolics (36.8 mg/ml). The topical application of EtSCT suppressed photoaging of the skin of UV-irradiated mice, and this was demonstrated by the inhibition of wrinkle formation, the suppression of the erythema index as well as the prevention of transepidermal water loss. Additionally, the epidermal thickness and adipocytes number were recovered to a similar level as that in the no radiation group in the UV + EtSCT‑treated groups compared with the UV + vehicle‑treated group, and the expression of collagen I increased. The attenuation of mitogen‑activated protein kinase and ER stress signaling pathways activated by reactive oxygen species was also detected in the UV + EtSCT‑treated group. Inflammatory responses including the infiltration of mast cells, CD31 expression and interleukin-6 secretion were significantly lower in the UV + EtSCT-treated groups. Moreover, the concentration of malondialdehyde was reduced and the activity of superoxide dismutase was effectively recovered in the UV + EtSCT-treated groups compared with that in the vehicle-treated groups. Liver and kidney toxicity factors were maintained at a constant level. These results suggest that EtSCT has the potential for

  8. Elucidation of the transport pathway in hairless rat skin enhanced by low-frequency sonophoresis based on the solute-water transport relationship and confocal microscopy.

    PubMed

    Morimoto, Yasunori; Mutoh, Mizue; Ueda, Hideo; Fang, Liang; Hirayama, Kotaro; Atobe, Mahito; Kobayashi, Daisuke

    2005-04-18

    In this study, we examined a relationship between hydrophilic solute and water (vehicle) transports in the excised hairless rat skin in the presence of ultrasound (41 kHz, 60-300 mW/cm2) irradiation and also conducted skin surface observation using confocal microscopy. When the applied intensity was increased stepwise over the rage of 60-300 mW/cm2, the transport of tritiated water (3H2O) was increased 140-fold in an intensity-dependent manner and this returned to normal on stopping the ultrasound application. The skin permeation clearance (mul/h) of model hydrophilic solutes, calcein (MW 623) and FITC-labeled dextrans [MW 4400 (FD-4) and MW 38000 (FD-40)], across the skin under the influence of ultrasound was plotted against the corresponding 3H2O flux (microl/h) to estimate the potential contribution of convective solvent flow, induced by the ultrasound application, to the solute transport. Good correlations were observed between the 3H2O flux and solute clearances and, unexpectedly, the slope values obtained from linear regression of the plots were consistent for all solutes examined (1.04+/-0.29 for calcein, 1.07+/-0.17 for FD-4, and 1.08+/-0.23 for FD-40, respectively). Transport of intact FD-4 and FD-40 was confirmed by gel permeation chromatography. When the skin surface and deeper regions of the skin after sonophoresis of FD-40 were observed using a confocal microscope, the fluorescence of FD-40 was uniformly distributed in the area under the ultrasound horn and also evident in crack-like structures in the boundary of the horn. On the other hand, a hexagonal structure of horny cells in the stratum corneum (SC) observed by post-staining with rhodamine B was fully conserved in the area under the horn. These findings suggest that 41 kHz ultrasound can increase the transdermal transport of hydrophilic solutes by inducing convective solvent flow probably via both corneocytes and SC lipids as well as newly developed routes. Our observation also suggests that 41 k

  9. Fractionated illumination after topical application of 5-aminolevulinic acid on normal skin of hairless mice: the influence of the dark interval.

    PubMed

    de Bruijn, H S; van der Ploeg-van den Heuvel, A; Sterenborg, H J C M; Robinson, D J

    2006-12-01

    We have previously shown that light fractionation during topical aminolevulinic acid based photodynamic therapy (ALA-PDT) with a dark interval of 2h leads to a significant increase in efficacy in both pre-clinical and clinical PDT. However this fractionated illumination scheme required an extended overall treatment time. Therefore we investigated the relationship between the dark interval and PDT response with the aim of reducing the overall treatment time without reducing the efficacy. Five groups of mice were treated with ALA-PDT using a single light fraction or the two-fold illumination scheme with a dark interval of 30 min, 1, 1.5 and 2h. Protoporphyrin IX fluorescence kinetics were monitored during illumination. Visual skin response was monitored in the first seven days after PDT and assessed as PDT response. The PDT response decreases with decreasing length of the dark interval. Only the dark interval of 2h showed significantly more damage compared to all the other dark intervals investigated (P<0.05 compared to 1.5h and P<0.01 compared to 1h, 30 min and a single illumination). No relationship could be shown between the utilized PpIX fluorescence during the two-fold illumination and the PDT response. The rate of photobleaching was comparable for the first and the second light fraction and not dependent of the length of dark interval used. We conclude that in the skin of the hairless mouse the dark interval cannot be reduced below 2h without a significant reduction in PDT efficacy.

  10. Chemopreventive effects of Calluna vulgaris and Vitis vinifera extracts on UVB-induced skin damage in SKH-1 hairless mice.

    PubMed

    Filip, A; Clichici, S; Daicoviciu, D; Catoi, C; Bolfa, P; Postescu, I D; Gal, A; Baldea, I; Gherman, C; Muresan, A

    2011-06-01

    Solar ultraviolet radiation (UV) is a major cause of non-melanoma skin cancer in humans. Photochemoprevention with natural products represents a simple but very effective strategy in the management of cutaneous neoplasia. The study investigated the protective activity of Calluna vulgaris (Cv) and red grape seeds (Vitis vinifera L, Burgund Mare variety) (BM) extracts in vivo on UVB-induced deleterious effects in SKH-1 mice skin. Forty SKH-1 mice were randomly divided into 4 groups (n=10): control, UVB irradiated, Cv + UVB irradiated, BM+UVB irradiated. Both extracts were applied topically on the skin in a dose of 4 mg/40 μl/cm(2) before UVB exposure - single dose. The effects were evaluated in skin 24 hours after irradiation through the presence of cyclobutane pyrimidine dimers (CPDs) and sunburn cells, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 levels. The antioxidant activity of BM extract was higher than those of Cv extract as determined using stable free radical DPPH assay and ABTS test. One single dose of UVB generated formation of CPDs (p<0.0001) and sunburn cells (p<0.0002) and increased the cytokine levels in skin (p<0.0001). Twenty hours following irradiation BM extract inhibited UVB-induced sunburn cells (p<0.02) and CPDs formation (p<0.0001). Pretreatment with Cv and BM extracts resulted in significantly reduced levels of IL-6 and TNF-α compared with UVB alone (p<0.0001). Our results suggest that BM extracts might be a potential candidate in preventing the damages induced by UV in skin.

  11. Injury Thresholds for Topical-Cream-Coated Skin of Hairless Guinea Pigs (cavia porcellus) in the Near Infrared Region

    DTIC Science & Technology

    2006-01-01

    Oler, and T.E. Johnson, "Comparison of two porcine { Sus scrofa domestica) skin models for in vivo near-infrared laser exposure," Comp. Med., 50, 391...Characterization of Porcine ( Sus scrofa domestica) Dermal Lesions Induced by 1540-nm Laser Radiation Pulses," Comparative Medicine 50(6), 633 - 638 (2000

  12. Cutaneous challenge with chemical warfare agents in the SKH-1 hairless mouse (II): effects of some currently used skin decontaminants (RSDL and Fuller's earth) against liquid sulphur mustard and VX exposure.

    PubMed

    Taysse, L; Dorandeu, F; Daulon, S; Foquin, A; Perrier, N; Lallement, G; Breton, P

    2011-06-01

    Using the hairless mouse screening model presented in the companion paper(1) the aim of this study was to assess two skin decontaminating systems: Fuller's earth (FE) and Reactive Skin Decontamination Lotion (RSDL) against two extremely toxic chemical warfare agents that represent a special percutaneous hazard, sulphur mustard (SM) and O-ethyl-S-(2[di-isopropylamino]ethyl)methyl-phosphonothioate (VX). Five minutes after being exposed on the back to either 2 µL of neat sulphur mustard or 50 µg.kg(-1) of diluted VX, mice were decontaminated. Both systems were able to reduce blisters 3 days after SM exposure. However, RSDL was found to be more efficient than FE in reducing the necrosis of the epidermis and erosion. In the case of VX exposure, RSDL, whatever the ratio of decontaminant to toxicant used (RSDL 10, 20, 50), was not able to sufficiently prevent the inhibition of plasma cholinesterases taken as a surrogate marker of exposure and toxicity. Only FE reduced significantly the ChE inhibition. Some of these observations are different from our previous results obtained in domestic swine and these changes are thus discussed in the perspective of using SKH-1 hairless mice for the initial in vivo screening of decontaminants.

  13. Tattoo removal in micropigs with low-energy pulses from a Q-switched Nd:YAG laser at 1064 nm

    NASA Astrophysics Data System (ADS)

    Hu, Xin-Hua; Wooden, W. A.; Cariveau, Mickael J.; Fang, Qiyin; Bradfield, J. F.; Kalmus, Gerhard W.; Vore, S. J.; Sun, Y.

    2001-05-01

    Treatment of pigmented lesions in skin with visible or near- infrared nanosecond (ns) laser pulses often causes significant collateral tissue damage because the current approach uses pulses with energy of 300 mJ or larger. Additionally, this requires large Q-switched laser systems. To overcome these disadvantages, we have investigated a different approach in delivering ns laser pulses for cutaneous lesion treatment. Tattoo removal in an animal model with a focused laser beam from a Q-switched Nd:YAG laser has been investigated in two Yucatan micropigs tattooed with blue, black, green and red pigments. The tattoos were treated with a focused beam of 12-ns pulses at 1064 nm, with different depth under the skin surface, while the micropig was translated to achieve an effect of single pulse per ablation site in the skin. With the pulse energy reduced to a range from 38 to 63 mJ, we found that nearly complete clearance was achieved for blue and black tattoos while clearance of red and green tattoos was incomplete. Analysis of the skin appearance suggested that the pulse energy can be decreased to below 20 mJ which may lead to further reduction of the collateral tissue damage and improve the clearance of red and green tattoos.

  14. Anti-wrinkle effects of Sargassum muticum ethyl acetate fraction on ultraviolet B-irradiated hairless mouse skin and mechanistic evaluation in the human HaCaT keratinocyte cell line

    PubMed Central

    Song, Jae Hyoung; Piao, Mei Jing; Han, Xia; Kang, Kyoung Ah; Kang, Hee Kyoung; Yoon, Weon Jong; Ko, Mi Hee; Lee, Nam Ho; Lee, Mi Young; Chae, Sungwook; Hyun, Jin Won

    2016-01-01

    The present study investigated the photoprotective properties of the ethyl acetate fraction of Sargassum muticum (SME) against ultraviolet B (UVB)-induced skin damage and photoaging in a mouse model. HR-1 strain hairless male mice were divided into three groups: An untreated control group, a UVB-irradiated vehicle group and a UVB-irradiated SME group. The UVB-irradiated mice in the SME group were orally administered with SME (100 mg/kg body weight in 0.1 ml water per day) and then exposed to radiation at a dose of 60–120 mJ/cm2. Wrinkle formation and skin damage were evaluated by analysis of skin replicas, epidermal thickness and collagen fiber integrity in the dermal connective tissue. The mechanism underlying the action of SME was also investigated in the human HaCaT keratinocyte cell line following exposure of the cells to UVB at a dose of 30 mJ/cm2. The protein expression levels and activity of matrix metalloproteinase-1 (MMP-1), and the binding of activator protein-1 (AP-1) to the MMP-1 promoter were assessed in the HaCaT cells using western blot analysis, an MMP-1 fluorescent assay and a chromatin immune-precipitation assay, respectively. The results showed that the mean length and depth of the wrinkles in the UVB-exposed hairless mice were significantly improved by oral administration of SME, which also prevented the increase in epidermal thickness triggered by UVB irradiation. Furthermore, a marked increase in collagen bundle formation was observed in the UVB-treated mice with SME administration. SME pretreatment also significantly inhibited the UVB-induced upregulation in the expression and activity of MMP-1 in the cultured HaCaT keratinocytes, and the UVB-enhanced association of AP-1 with the MMP-1 promoter. These results suggested that SME may be useful as an anti-photoaging resource for the skin. PMID:27573915

  15. UV radiation-induced skin aging in hairless mice is effectively prevented by oral intake of sea buckthorn (Hippophae rhamnoides L.) fruit blend for 6 weeks through MMP suppression and increase of SOD activity.

    PubMed

    Hwang, In Sik; Kim, Ji Eun; Choi, Sun Il; Lee, Hye Ryun; Lee, Young Ju; Jang, Min Ju; Son, Hong Ju; Lee, Hee Seob; Oh, Chung Hun; Kim, Bae Hwan; Lee, Sang Hak; Hwang, Dae Youn

    2012-08-01

    Oxidative stress and oxidative photodamage induced by UV radiation can cause serious skin damage that is characterized by wrinkling, roughness, laxity and pigmentation. The effects of a sea buckthorn (Hippophae rhamnoides L.) fruit blend (SFB) containing sea buckthorn fruit extract, blueberry extract and collagen on UV-induced skin aging were examined by treating hairless mice for 6 weeks with UV irradiation and SFB administered orally. The effects of SFB were measured in the skin of these mice by phenotypical and histological analysis and western blotting. According to wrinkle formation analysis, the oral intake of SFB induced a decrease in wrinkle formation in the damaged skin of UV-irradiated mice. The thickness of the epidermis and dermis in the vitamin extracts (Vit)- and SFB-treated group was lower than that in the vehicle-treated group, but the group treated with SFB50 was the most effective group. The mice treated with the Vit- or SFB solution maintained a normal moisture content through the inhibition of transdermal water loss (TEWL) and an increase in skin moisture content. Furthermore, the levels of matrix metalloproteinase (MMP) and collagen protein expression were assessed in five groups to examine the mechanisms underlying the effects of SFB oral intake. The application of SFB induced a decrease in MMP-1 and -9 expression to the levels observed in the vehicle-treated group, but MMP-9 expression showed a much larger decrease than MMP-1. Furthermore, the expression of collagen-1 in the skin corresponded to MMP expression except for the SFB30-treated group, whereas the superoxide dismutase (SOD) activity was increased dramatically in the SFB50-treated group. These results suggest that SFB has potential as a protective and therapeutic drug candidate against skin aging that functions by regulating the moisture content, MMP expression levels and SOD activity.

  16. Anti-wrinkle effects of Sargassum muticum ethyl acetate fraction on ultraviolet B-irradiated hairless mouse skin and mechanistic evaluation in the human HaCaT keratinocyte cell line.

    PubMed

    Song, Jae Hyoung; Piao, Mei Jing; Han, Xia; Kang, Kyoung Ah; Kang, Hee Kyoung; Yoon, Weon Jong; Ko, Mi Hee; Lee, Nam Ho; Lee, Mi Young; Chae, Sungwook; Hyun, Jin Won

    2016-10-01

    The present study investigated the photoprotective properties of the ethyl acetate fraction of Sargassum muticum (SME) against ultraviolet B (UVB)‑induced skin damage and photoaging in a mouse model. HR‑1 strain hairless male mice were divided into three groups: An untreated control group, a UVB‑irradiated vehicle group and a UVB‑irradiated SME group. The UVB‑irradiated mice in the SME group were orally administered with SME (100 mg/kg body weight in 0.1 ml water per day) and then exposed to radiation at a dose of 60‑120 mJ/cm2. Wrinkle formation and skin damage were evaluated by analysis of skin replicas, epidermal thickness and collagen fiber integrity in the dermal connective tissue. The mechanism underlying the action of SME was also investigated in the human HaCaT keratinocyte cell line following exposure of the cells to UVB at a dose of 30 mJ/cm2. The protein expression levels and activity of matrix metalloproteinase‑1 (MMP‑1), and the binding of activator protein‑1 (AP‑1) to the MMP‑1 promoter were assessed in the HaCaT cells using western blot analysis, an MMP‑1 fluorescent assay and a chromatin immune‑precipitation assay, respectively. The results showed that the mean length and depth of the wrinkles in the UVB‑exposed hairless mice were significantly improved by oral administration of SME, which also prevented the increase in epidermal thickness triggered by UVB irradiation. Furthermore, a marked increase in collagen bundle formation was observed in the UVB‑treated mice with SME administration. SME pretreatment also significantly inhibited the UVB‑induced upregulation in the expression and activity of MMP‑1 in the cultured HaCaT keratinocytes, and the UVB‑enhanced association of AP‑1 with the MMP‑1 promoter. These results suggested that SME may be useful as an anti-photoaging resource for the skin.

  17. Impact of Cosmetic Lotions on Nanoparticle Penetration through ex vivo C57BL/6 Hairless Mouse and Human Skin: A Comparison Study

    PubMed Central

    Jatana, Samreen; Callahan, Linda M.; Pentland, Alice P.; DeLouise, Lisa A.

    2016-01-01

    Understanding the interactions of nanoparticles (NPs) with skin is important from a consumer and occupational health and safety perspective, as well as for the design of effective NP-based transdermal therapeutics. Despite intense efforts to elucidate the conditions that permit NP penetration, there remains a lack of translatable results from animal models to human skin. The objectives of this study are to investigate the impact of common skin lotions on NP penetration and to quantify penetration differences of quantum dot (QD) NPs between freshly excised human and mouse skin. QDs were mixed in 7 different vehicles, including 5 commercial skin lotions. These were topically applied to skin using two exposure methods; a petri dish protocol and a Franz diffusion cell protocol. QD presence in the skin was quantified using Confocal Laser Scanning Microscopy. Results show that the commercial vehicles can significantly impact QD penetration in both mouse and human skin. Lotions that contain alpha hydroxyl acids (AHA) facilitated NP penetration. Lower QD signal was observed in skin studied using a Franz cell. Freshly excised human skin was also studied immediately after the sub-cutaneous fat removal process, then after 24 hours rest ex vivo. Resting human skin 24 hours prior to QD exposure significantly reduced epidermal presence. This study exemplifies how application vehicles, skin processing and the exposure protocol can affect QD penetration results and the conclusions that maybe drawn between skin models. PMID:27453793

  18. Characterization of Motor and Somatosensory Evoked Potentials in the Yucatan Micropig Using Transcranial and Epidural Stimulation.

    PubMed

    Benavides, Francisco D; Santamaria, Andrea J; Bodoukhin, Nikita; Guada, Luis G; Solano, Juan P; Guest, James D

    2016-11-28

    Yucatan micropigs have brain and spinal cord dimensions similar to humans and are useful for certain spinal cord injury (SCI) translational studies. Micropigs are readily trained in behavioral tasks, allowing consistent testing of locomotor loss and recovery. However, there has been little description of their motor and sensory pathway neurophysiology. We established methods to assess motor and sensory cortical evoked potentials in the anesthetized, uninjured state. We also evaluated epidurally evoked motor and sensory stimuli from the T6 and T9 levels, spanning the intended contusion injury epicenter. Response detection frequency, mean latency and amplitude values, and variability of evoked potentials were determined. Somatosensory evoked potentials were reliable and best detected during stimulation of peripheral nerve and epidural stimulation by referencing the lateral cortex to midline Fz. The most reliable hindlimb motor evoked potential (MEP) occurred in tibialis anterior. We found MEPs in forelimb muscles in response to thoracic epidural stimulation likely generated from propriospinal pathways. Cranially stimulated MEPs were easier to evoke in the upper limbs than in the hindlimbs. Autopsy studies revealed substantial variations in cortical morphology between animals. This electrophysiological study establishes that neurophysiological measures can be reliably obtained in micropigs in a time frame compatible with other experimental procedures, such as SCI and transplantation. It underscores the need to better understand the motor control pathways, including the corticospinal tract, to determine which therapeutics are suitable for testing in the pig model.

  19. Interactions of ethanol and folate deficiency in development of alcoholic liver disease in the micropig.

    PubMed Central

    Halsted, Charles H.; Villanueva, Jesus A.; Devlin, Angela M.; James, S. Jill

    2002-01-01

    Folate deficiency is present in most patients with alcoholic liver disease (ALD), whereas folate regulates and alcoholism perturbs intrahepatic methionine metabolism, and S-adenosyl-methionine prevents the development of experimental ALD. Our studies explored the hypothesis that abnormal methionine metabolism is exacerbated by folate deficiency and promotes the development of ALD in the setting of chronic ethanol exposure. Using the micropig animal model, dietary combinations of folate deficiency and a diet containing 40% of kcal as ethanol were followed by measurements of hepatic methionine metabolism and indices of ALD. Alcoholic liver injury, expressed as steatohepatitis in terminal 14 week liver specimens, was evident in micropigs fed the combined ethanol containing and folate deficient diet but not in micropigs fed each diet separately. Perturbations of methionine metabolism included decreased hepatic S-adenosylmethionine and glutathione with increased products of DNA and lipid oxidation. Thus, the development of ALD is linked to abnormal methionine metabolism and is accelerated in the presence of folate deficiency. PMID:12053707

  20. Ultraviolet radiation-induced non-melanoma skin cancer in the Crl:SKH1:hr-BR hairless mouse: augmentation of tumor multiplicity by chlorophyllin and protection by indole-3-carbinol.

    PubMed

    Cope, R B; Loehr, C; Dashwood, R; Kerkvliet, N I

    2006-05-01

    Over 1 million new cases of ultraviolet radiation-induced non-melanoma skin cancers (NMSC) per year now occur in the USA and the incidence of these diseases continues to increase. New preventative strategies are required. The hypothesis tested was that dietary administration of the putative cancer chemopreventatives sodium-copper-chlorophyllin (Chlor) or indole-3-carbinol (I3C) would inhibit UV-induced skin carcinogenesis in the Crl:SKH1:hr-BR hairless mouse. Groups of 20 mice were pre-fed isocaloric/isonutritive 20% corn-oil AIN-76a based diets that contained either Chlor (1.52 g%), I3C (5.08 g%) or no chemopreventative (control) for 2 weeks followed by exposure of their dorsal skin to a 10 week incremental, sub-erythemal, carcinogenic simulated solar UV exposure regime. Feeding was continued for the duration of the experiment. Matched non-UV exposed dietary groups were also included in the experimental design. The diets had no significant (p > 0.05) effect on body weight, feed consumption, cutaneous methanol-extractable UV photoprotective substances or on cutaneous UV-reflective characteristics. By day 180, UV-irradiated mice fed the Chlor had a significantly (p < 0.05) higher tumor multiplicity (33.6 +/- 4.72; mean +/- SEM) than UV-irradiated control animals (22.8 +/- 4.25). UV-irradiated mice fed I3C had a significantly (p < 0.001) lower tumor multiplicity (13.0 +/- 2.42) than that of both the UV-irradiated control and UV-irradiated Chlor-fed mice. The Chlor or I3C diets did not significantly (p > 0.05) affect UV-induced systemic suppression of contact hypersensitivity responses. These results demonstrate augmentation of the UV-induced cutaneous carcinogenic process by dietary chlorophyllin and protection from this carcinogenic process by indole-3-carbinol via mechanisms that do not involve changes in skin optical properties, modulation of photoimmunosuppression or caloric/nutrient effects.

  1. Silibinin inhibits ultraviolet B radiation-induced DNA-damage and apoptosis by enhancing interleukin-12 expression in JB6 cells and SKH-1 hairless mouse skin.

    PubMed

    Narayanapillai, Sreekanth; Agarwal, Chapla; Deep, Gagan; Agarwal, Rajesh

    2014-06-01

    Recent studies have demonstrated silibinin efficacy against ultraviolet B (UVB)-induced skin carcinogenesis via different mechanisms in cell lines and animal models; however, its role in regulating interleukin-12 (IL-12), an immunomodulatory cytokine that reduces UVB-induced DNA damage and apoptosis, is not known. Here, we report that UVB irradiation causes caspase 3 and PARP cleavage and apoptosis, and addition of recombinant IL-12 or silibinin immediately after UVB significantly protects UVB-induced apoptosis in JB6 cells. IL-12 antibody-mediated blocking of IL-12 activity compromised the protective effects of both IL-12 and silibinin. Both silibinin and IL-12 also accelerated the repair of UVB-caused cyclobutane-pyrimidine dimers (CPDs) in JB6 cells. Additional studies confirmed that indeed silibinin causes a significant increase in IL-12 levels in UVB-irradiated JB6 cells as well as in mouse skin epidermis, and that similar to cell-culture findings, silibinin topical application immediately after UVB exposure causes a strong protection against UVB-induced TUNEL positive cells in epidermis possibly through a significantly accelerated repair of UVB-caused CPDs. Together, these findings for the first time provide an important insight regarding the pharmacological mechanism wherein silibinin induces endogenous IL-12 in its efficacy against UVB-caused skin damages. In view of the fact that an enhanced endogenous IL-12 level could effectively remove UVB-caused DNA damage and associated skin cancer, our findings suggest that the use of silibinin in UVB-damaged human skin would also be a practical and translational strategy to manage solar radiation-caused skin damages as well as skin cancer.

  2. Recapitulation of the hairless mouse phenotype using catalytic oligonucleotides: implications for permanent hair removal.

    PubMed

    Cserhalmi-Friedman, Peter B; Panteleyev, Andrey A; Christiano, Angela M

    2004-03-01

    Ribozyme technology is widely used to target mRNA in a sequence-specific fashion and thus change the expression pattern of cells or tissues. While the goal of mRNA targeting is usually the cleavage of mutant mRNAs with the prospect of gene therapy for inherited diseases, in certain instances, targeting of wild-type genes can be used therapeutically. Lack of expression of the mouse hairless gene due to inherited mutations leads to the complete and irreversible loss of hair known as atrichia. We designed this study to recapitulate the hairless phenotype in a restricted manner by topical application of deoxyribozyme-targeting molecules to specifically cleave the mouse hairless mRNA. Histological samples taken from treated skin at different times demonstrated a decreased number of hair follicles, an involution of the remaining follicles, a separation of the dermal papillae, and the presence of dermal cysts, all characteristics of the hairless phenotype, but not normally present in the skin of C57Bl/6 J mice. In this study, we successfully recapitulated the hairless phenotype using topically applied target-specific catalytic oligonucleotides designed to cleave the mouse hairless mRNA. Our results demonstrate the feasibility of using ribozyme technology to alter the gene expression in the skin via topical application and provide proof of principle for the development of this strategy for permanent hair removal.

  3. Induction of pyrimidine dimers in epidermal DNA of hairless mice by UVB: an action spectrum

    SciTech Connect

    Ley, R.D.; Peak, M.J.; Lyon, L.L.

    1983-03-01

    An action spectrum for the induction of pyrimidine dimers in the epidermis of hairless mice was determined between 288 and 307 nm. The presence of pyrimidine dimers in tritium-labeled DNA extracted from exposed SKH:hairless-1 mouse skin was determined using dimer-specific nucleases from Micrococcus luteus in conjunction with sedimentation of the irradiated DNA in alkaline sucrose gradients. The rate of induction of pyrimidine dimers was maximal at 293 nm. These values were used to propose a UVB transmission curve for mouse epidermis.

  4. Psoralen-containing sunscreen is tumorigenic in hairless mice

    SciTech Connect

    Cartwright, L.E.; Walter, J.F.

    1983-06-01

    Sunscreens containing 5-methoxypsoralen (5-MOP) are currently being marketed to promote tanning by inducing psoralen-mediated ultraviolet (UV) A (320-400 nm) melanogenesis. The rationale is that this may prevent UVB (290-320 nm) radiation-induced skin damage. However, mouse studies have shown that 5-MOP has the same cutaneous photocarcinogenic potential as 8-methoxypsoralen. In addition, the 5-MOP--containing sunscreen Sun System III (SS III), when combined with UVA, induces epidermal ornithine decarboxylase activity, an enzyme associated with tumor promotion. Therefore, we investigated whether SS III had sufficient psoralen concentration to be tumorigenic in hairless mice exposed to chronic, intermittent UVA radiation. SS III was applied to hairless mice 5 days per week for 20 weeks. After each application the mice were exposed to 2.5 to 10 joules/cm2 UVA radiation. All test groups developed atypical squamous papillomas in direct proportion to the dosage of UVA radiation received. A shorter latency period for tumor development was seen with larger UVA doses. Test animals followed up to 1 year developed invasive squamous cell tumors. Control groups (SS III without UVA and UVA without SS III) remained free of tumors. Animals receiving SS III plus UVA developed persistent skin thickening and increased dermal cyst formation similar to that reported with chronic exposure to UVB, a known carcinogenic wavelength.

  5. 90-day dietary toxicity study with esterified propoxylated glycerol (EPG) in micropigs.

    PubMed

    Wedig, John; Bechtel, David H

    2014-12-01

    The subchronic (90-day) toxicity of esterified propoxylated glycerol (EPG) was assessed in micropigs. Animals (5/sex/group) received feed containing 5%, 10%, and 17% EPG, mixed accordingly throughout the study to deliver 1.5, 3, and 5 g/kg bw/day of EPG, respectively. Corn oil served as the vehicle control (0 g/kg bw/day). Subsets of animals were evaluated at Week 6; the remainder between Weeks 12 and 14. With the exception of liver and serum vitamin levels, statistically significant difference between control and EPG groups were seen sporadically, and with no apparent connection to treatment and/or no consistency across time intervals. EPG intakes of 3 and 5 g/kg bw/day, but not at 1.5 g/kg bw/day were associated with significantly lower serum 25-OH vitamin D levels. Serum total vitamin D levels were significantly lower across all EPG groups. There were also trends toward lower levels of liver vitamins A and E among EPG-treated animals, but the effects were less consistent. The effects on vitamin levels observed in EPG-treated animals were not accompanied by any signs of vitamin deficiency (e.g., effects on growth, clinical signs, or clinical pathology), and might have been related to the larger mass of EPG acting as a lipid "sink" during transit in the gastrointestinal tract.

  6. Connective tissue photodamage in the hairless mouse is partially reversible.

    PubMed

    Kligman, L H

    1987-03-01

    Photodamaged connective tissue in animal and human skin is characterized by excessive accumulations of elastic fibers, loss of mature collagen, concomitant overproduction of new collagen, and greatly increased levels of glycosaminoglycans. Formerly considered irreversible changes, we recently showed in hairless mice, post irradiation, that a band of normal connective tissue was laid down subepidermally. The present studies focused on 2 aspects of this repair: whether repair would occur if animals were protected by sunscreens after dermal damage was induced and irradiation continued; whether retinoic acid could enhance the repair process. To examine the first aspect, albino hairless mice were irradiated with Westinghouse FS 20 sunlamps thrice weekly for 30 weeks. Sunscreens of high sun-protection factors were applied after 10 and 20 weeks. Not only was further damage prevented, but the damage incurred before sunscreen application was repaired. This appeared as subepidermal reconstruction zones containing normal, mature collagen and a network of fine elastic fibers. The second aspect was examined by applying 0.05% retinoic acid, topically, to animals preirradiated for 10 weeks. In contrast to controls treated with vehicle, the reconstruction zone was significantly wider in retinoic acid-treated mice. The enhanced repair was dose-related.

  7. Connective tissue photodamage in the hairless mouse is partially reversible

    SciTech Connect

    Kligman, L.H.

    1987-03-01

    Photodamaged connective tissue in animal and human skin is characterized by excessive accumulations of elastic fibers, loss of mature collagen, concomitant overproduction of new collagen, and greatly increased levels of glycosaminoglycans. Formerly considered irreversible changes, we recently showed in hairless mice, post irradiation, that a band of normal connective tissue was laid down subepidermally. The present studies focused on 2 aspects of this repair: whether repair would occur if animals were protected by sunscreens after dermal damage was induced and irradiation continued; whether retinoic acid could enhance the repair process. To examine the first aspect, albino hairless mice were irradiated with Westinghouse FS 20 sunlamps thrice weekly for 30 weeks. Sunscreens of high sun-protection factors were applied after 10 and 20 weeks. Not only was further damage prevented, but the damage incurred before sunscreen application was repaired. This appeared as subepidermal reconstruction zones containing normal, mature collagen and a network of fine elastic fibers. The second aspect was examined by applying 0.05% retinoic acid, topically, to animals preirradiated for 10 weeks. In contrast to controls treated with vehicle, the reconstruction zone was significantly wider in retinoic acid-treated mice. The enhanced repair was dose-related.

  8. The thymus of the hairless rhino-j (hr/hr-j) mice

    PubMed Central

    SAN JOSE, I.; GARCÍA-SUÁREZ, O.; HANNESTAD, J.; CABO, R.; GAUNA, L.; REPRESA, J.; VEGA, J. A.

    2001-01-01

    The hairless (hr) gene is expressed in a large number of tissues, primarily the skin, and a mutation in the hr gene is responsible for the typical cutaneous phenotype of hairless mice. Mutant hr mouse strains show immune defects involving especially T cells and macrophages, as well as an age-related immunodeficiency and an accelerated atrophy of the thymus. These data suggest that the hr mutation causes a defect of this organ, although hr transcripts have not been detected in fetal or adult mice thymus. The present study analyses the thymus of young (3 mo) and adult (9 mo) homozygous hr-rh-j mice (a strain of hairless mice) by means of structural techniques and immunohistochemistry to selectively identify thymic epithelial cells, dendritic cells, and macrophages. There were structural alterations in the thymus of both young and adult rh-rh-j mice, which were more severe in older animals. These alterations consisted of relative cortical atrophy, enlargement of blood vessels, proliferation of perivascular connective tissue, and the appearance of cysts. hr-rh-j mice also showed a decrease in the number of epithelial and dendritic cells, and macrophages. Taken together, present results strongly suggest degeneration and accelerated age-dependent regression of the thymus in hr-rh-j mice, which could explain at least in part the immune defects reported in hairless mouse strains. PMID:11327202

  9. Effect of oral administration of Lactobacillus plantarum HY7714 on epidermal hydration in ultraviolet B-irradiated hairless mice.

    PubMed

    Ra, Jehyeon; Lee, Dong Eun; Kim, Sung Hwan; Jeong, Ji-Woong; Ku, Hyung Keun; Kim, Tae-Youl; Choi, Il-Dong; Jeung, Woonhee; Sim, Jae-Hun; Ahn, Young-Tae

    2014-12-28

    In this study, we evaluated the effect of Lactobacillus plantarum HY7714 on skin hydration in human dermal fibroblasts and in hairless mice. In Hs68 cells, L. plantarum HY7714 not only increased the serine palmitoyltransferase (SPT) mRNA level, but also decreased the ceramidase mRNA level. In order to confirm the hydrating effects of L. plantarum HY7714 in vivo, we orally administered vehicle or L. plantarum HY7714 at a dose of 1 × 10(9) CFU/day to hairless mice for 8 weeks. In hairless mice, L. plantarum HY7714 decreased UVB-induced epidermal thickness. In addition, we found that L. plantarum HY7714 administration suppressed the increase in transepidermal water loss and decrease in skin hydration, which reflects barrier function fluctuations following UV irradiation. In particular, L. plantarum HY7714 administration increased the ceramide level compared with that in the UVB group. In the experiment on SPT and ceramidase mRNA expressions, L. plantarum HY7714 administration improved the reduction in SPT mRNA levels and suppressed the increase in ceramidase mRNA levels caused by UVB in the hairless mice skins. Collectively, these results suggest that L. plantarum HY7714 can be a potential candidate for preserving skin hydration levels against UV irradiation.

  10. Folate deficiency disturbs hepatic methionine metabolism and promotes liver injury in the ethanol-fed micropig.

    PubMed

    Halsted, Charles H; Villanueva, Jesus A; Devlin, Angela M; Niemelä, Onni; Parkkila, Seppo; Garrow, Timothy A; Wallock, Lynn M; Shigenaga, Mark K; Melnyk, Stepan; James, S Jill

    2002-07-23

    Alcoholic liver disease is associated with abnormal hepatic methionine metabolism and folate deficiency. Because folate is integral to the methionine cycle, its deficiency could promote alcoholic liver disease by enhancing ethanol-induced perturbations of hepatic methionine metabolism and DNA damage. We grouped 24 juvenile micropigs to receive folate-sufficient (FS) or folate-depleted (FD) diets or the same diets containing 40% of energy as ethanol (FSE and FDE) for 14 wk, and the significance of differences among the groups was determined by ANOVA. Plasma homocysteine levels were increased in all experimental groups from 6 wk onward and were greatest in FDE. Ethanol feeding reduced liver methionine synthase activity, S-adenosylmethionine (SAM), and glutathione, and elevated plasma malondialdehyde (MDA) and alanine transaminase. Folate deficiency decreased liver folate levels and increased global DNA hypomethylation. Ethanol feeding and folate deficiency acted together to decrease the liver SAM/S-adenosylhomocysteine (SAH) ratio and to increase liver SAH, DNA strand breaks, urinary 8-oxo-2'-deoxyguanosine [oxo(8)dG]/mg of creatinine, plasma homocysteine, and aspartate transaminase by more than 8-fold. Liver SAM correlated positively with glutathione, which correlated negatively with plasma MDA and urinary oxo(8)dG. Liver SAM/SAH correlated negatively with DNA strand breaks, which correlated with urinary oxo(8)dG. Livers from ethanol-fed animals showed increased centrilobular CYP2E1 and protein adducts with acetaldehyde and MDA. Steatohepatitis occurred in five of six pigs in FDE but not in the other groups. In summary, folate deficiency enhances perturbations in hepatic methionine metabolism and DNA damage while promoting alcoholic liver injury.

  11. Arterial insulin resistance in Yucatan micropigs with diet-induced obesity and metabolic syndrome

    PubMed Central

    Low Wang, Cecilia C.; Lu, Li; Leitner, J. Wayne; Sarraf, Mohammad; Gianani, Roberto; Draznin, Boris; Greyson, Clifford R.; Reusch, Jane E. B.; Schwartz, Gregory G.

    2013-01-01

    Aim Metabolic syndrome affects a large proportion of the population and increases cardiovascular disease risk. Because metabolic syndrome often co-exists clinically with atherosclerosis, it is difficult to distinguish their respective contributions to vascular abnormalities. Accordingly, we utilized a porcine dietary model of metabolic syndrome without atherosclerosis to investigate early abnormalities of vascular function and signaling. Methods Thirty-two Yucatan micropigs were fed either a high fat, high simple sugar, high calorie (HFHS) or standard chow diet (STD) for 6 months. Neither diet contained added cholesterol. Blood pressure and flow-mediated vasodilatation were assessed at baseline and 6 months. Aortas were harvested at 6 months to assess histology, insulin signaling, and endothelial nitric oxide (eNOS) phosphorylation. Results HFHS pigs developed characteristic of metabolic syndrome including obesity, dyslipidemia, and insulin resistance, but without histological evidence of atherosclerosis. Although arterial intima-media thickness did not differ between groups, vascular dysfunction in HFHS was manifest by increased blood pressure and impaired flow-mediated vasodilation of the femoral artery. Compared with STD, aortas from HFHS exhibited increased p85α expression and Ser307 IRS-1 phosphorylation, and blunted insulin-stimulated IRS-1-associated phosphatidylinositol (PI) 3-kinase activity. In the absence of insulin stimulation, aortic Akt Ser473-phosphorylation was greater in HFHS than in STD. With insulin stimulation, Akt phosphorylation increased in STD, but not HFHS. Insulin-induced Ser1177-phosphorylation of eNOS was decreased in HFHS, compared with STD. Conclusions Pigs with metabolic syndrome develop early vascular dysfunction and aortic insulin signaling abnormalities, and could be a useful model for early human vascular abnormalities in this condition. PMID:23558108

  12. Micro-PIGE determination of fluorine distribution in developing hamster tooth germs.

    PubMed

    Lyaruu, D M; Lenglet, W J; Wöltgens, J H; Bronckers, A L

    1989-05-01

    A micro-PIGE (Proton-Induced gamma-ray Emission) technique based on the delayed 5/2+----1/2+ nuclear transition of fluorine (E gamma = 197 keV, t1/2 = 87 ns) emitted after 19F(p,p', gamma)19F reaction was used to detect and study the distribution of fluorine in the developing enamel organ during pre-eruptive stages, i.e., the transitional to early maturation stages of enamel formation in neonatal hamsters administered a single IP dose of sodium fluoride (20 mg NaF/kg body weight). The aforementioned nuclear reaction is unique for fluorine, and therefore detection of gamma-rays emanating from this reaction in a biological specimen implies a positive identification of fluorine at that particular site. Calcium and phosphorus X-rays were also recorded and used as parameters for assessment of the relationship between the degree of mineralization and fluoride incorporation into the enamel organ. The highest fluorine concentration in the enamel organ was recorded in the dentin near the dentin-enamel junction (DEJ). In the enamel, the highest concentration of fluorine was found to be associated with the more mature areas of the enamel near the DEJ, but gradually decreased in the direction of the enamel surface. Fluorine was not detected in the control germs. These results suggest that administration of fluoride in high doses during the pre-eruptive stages of enamel formation leads to incorporation of the ion into the forming dentin and enamel mineral, and that the enamel matrix does not seem to bind fluoride avidly.

  13. Oral administration of Lactobacillus plantarum HY7714 protects hairless mouse against ultraviolet B-induced photoaging.

    PubMed

    Kim, Hyun Mee; Lee, Dong Eun; Park, Soo Dong; Kim, Yong-Tae; Kim, Yu Jin; Jeong, Ji Woong; Jang, Sung Sik; Ahn, Young-Tae; Sim, Jae-Hun; Huh, Chul-Sung; Chung, Dae Kyun; Lee, Jung-Hee

    2014-11-28

    Ultraviolet (UV) irradiation alters multiple molecular pathways in the skin, thereby inducing skin damage, including photoaging. In recent years, probiotics have gained interest due to their beneficial effects on skin health, such as inhibiting atopic dermatitis and improving skin immunity or inflammation. However, little is known about the effects of probiotics on UVBinduced photoaging. In this study, we evaluated the effect of Lactobacillus plantarum HY7714 against UVB-induced photoaging in human dermal fibroblasts and hairless mice. The results showed that L. plantarum HY7714 treatment effectively rescued UVB-reduced procollagen expression through the inhibition of UVB-induced matrix metalloproteinase (MMP)-1 expression in human dermal fibroblasts. Data from a western blot showed that L. plantarum HY7714 inhibited the phosphorylation of Jun N-terminal kinase, thereby suppressing the UVB-induced phosphorylation and expression of c-Jun. Oral administration of L. plantarum HY7714 clearly inhibited the number, depth, and area of wrinkles in hairless mouse skin. Histological data showed that L. plantarum HY7714 significantly inhibited UVB-induced epidermal thickness in mice. Western blot and zymography data also revealed that L. plantarum HY7714 effectively inhibited MMP-13 expression as well as MMP-2 and -9 activities in dermal tissue. Collectively, these results provide further insight regarding the skin biological actions of L. plantarum HY7714, a potential skin anti-photoaging agent.

  14. X-rays and photocarcinogenesis in hairless mice.

    PubMed

    Lerche, Catharina M; Philipsen, Peter A; Wulf, Hans Christian

    2013-08-01

    It is well known that excessive X-ray radiation can cause non-melanoma skin cancers. With the increased incidence of sun-related skin cancer there is a need to investigate the combination of sunlight and X-rays. Immunocompetent C3.Cg/TifBomTac mice (n = 298) were divided into 12 groups. Mice were irradiated with 12, 29 or 50 kV X-rays. The mice received a total dose of 45 Gy. They were irradiated with 3 SED simulated solar radiation (SSR) either before or after irradiation with X-rays. The groups irradiated with X-rays alone, 0, 3, 9 and 10 mice (0, 12, 29 and 50 kV, respectively) developed squamous cell carcinoma. In the groups irradiated with SSR after X-rays the development of tumours was significantly faster in the 50 kV group than in the corresponding control group (175 vs. 194 days, p < 0.001). In the groups irradiated with SSR prior to the X-ray radiation the development of tumours was significantly faster in the 29 and the 50 kV groups than in the corresponding control group (175 vs. 202 days, p < 0.001 and 158 vs. 202 days, p < 0.001, respectively). In conclusion, X-ray radiation alone is a weak carcinogen in hairless mice. There is an added carcinogenic effect if X-ray radiation is given on prior sun-exposed skin or if the skin is sun-exposed after X-rays. We still believe that X-ray radiation is a safe and effective therapy for various dermatological diseases but caution should be observed if a patient has severely sun-damaged skin or has a high-risk sun behaviour.

  15. Sulfur Mustard Induces Immune Sensitization in Hairless Guinea Pigs

    PubMed Central

    Mishra, Neerad C.; Rir-sima-ah, Jules; March, Thomas; Weber, Waylon; Benson, Janet; Jaramillo, Richard; Seagrave, Jean-Clare; Schultz, Gregory; Grotendorst, Gary; Sopori, Mohan

    2009-01-01

    Sulfur mustard (SM, bis-(2-chloroethyl) sulfide) is a well known chemical warfare agent that may cause long-term debilitating injury. Because of the ease of production and storage, it has a strong potential for chemical terrorism; however, the mechanism by which SM causes chronic tissue damage is essentially unknown. SM is a potent protein alkylating agent, and we tested the possibility that SM modifies cellular antigens, leading to an immunological response to “altered self” and a potential long-term injury. To that end, in this communication, we show that dermal exposure of euthymic hairless guinea pigs induced infiltration of both CD4+ and CD8+ T cells into the SM-exposed skin and strong upregulated expression of proinflammatory cytokines and chemokines (TNF-α, IFN-γ, and IL-8) in distal tissues such as the lung and the lymph nodes. Moreover, we present evidence for the first time that SM induces a specific delayed-type hypersensitivity response that is associated with splenomegaly, lymphadenopathy, and proliferation of cells in these tissues. These results clearly suggest that dermal exposure to SM leads to immune activation, infiltration of T cells into the SM-exposed skin, delayed-type hypersensitivity response, and molecular imprints of inflammation in tissues distal from the site of SM exposure. These immunological responses may contribute to the long-term sequelae of SM toxicity. PMID:19887117

  16. Sulfur mustard induces immune sensitization in hairless guinea pigs.

    PubMed

    Mishra, Neerad C; Rir-sima-ah, Jules; March, Thomas; Weber, Waylon; Benson, Janet; Jaramillo, Richard; Seagrave, Jean-Clare; Schultz, Gregory; Grotendorst, Gary; Sopori, Mohan

    2010-02-01

    Sulfur mustard (SM, bis-(2-chloroethyl) sulfide) is a well known chemical warfare agent that may cause long-term debilitating injury. Because of the ease of production and storage, it has a strong potential for chemical terrorism; however, the mechanism by which SM causes chronic tissue damage is essentially unknown. SM is a potent protein alkylating agent, and we tested the possibility that SM modifies cellular antigens, leading to an immunological response to "altered self" and a potential long-term injury. To that end, in this communication, we show that dermal exposure of euthymic hairless guinea pigs induced infiltration of both CD4(+) and CD8(+) T cells into the SM-exposed skin and strong upregulated expression of proinflammatory cytokines and chemokines (TNF-alpha, IFN-gamma, and IL-8) in distal tissues such as the lung and the lymph nodes. Moreover, we present evidence for the first time that SM induces a specific delayed-type hypersensitivity response that is associated with splenomegaly, lymphadenopathy, and proliferation of cells in these tissues. These results clearly suggest that dermal exposure to SM leads to immune activation, infiltration of T cells into the SM-exposed skin, delayed-type hypersensitivity response, and molecular imprints of inflammation in tissues distal from the site of SM exposure. These immunological responses may contribute to the long-term sequelae of SM toxicity.

  17. The potential application of hairless guinea pigs as a replacement for the Yucatan mini-pig in animal studies

    NASA Astrophysics Data System (ADS)

    Jindra, Nichole M.; Imholte, Michelle L.

    2008-02-01

    The Yucatan mini-pig (Sus scrofa) is one of the most widely used animal models for skin damage studies because it shares many of the same physical properties as human skin. While the Yucatan is ideal for laser exposure studies using a large spot size, its size and cost are excessive for projects using smaller beams. This experiment performed histological analysis of skin biopsies from pigmented Hairless Guinea Pigs (Cavia porcellus) for epidermal thickness and melanin concentration. That data was then compared to similar information on the Yucatan.

  18. The Potential Application of Hairless Guinea Pigs as a Replacement for the Yucatan Mini-pig in Animal Studies

    DTIC Science & Technology

    2009-02-01

    to normal biological processes like wound healing and toxicology 3,4,5 . Many of the papers stated that HGPs have similar skin properties as humans...albino HGP (genetically engineered by Canadian scientists for dermatological studies) and the normal haired variety. While not completely hairless, the...with HGP 8 DISTRIBUTION A, APPROVED FOR PUBLIC RELEASE; DISTRIBUTION UNLIMITED blood. With the increased interest in proteomic studies, these

  19. Noncontrast and contrast enhanced MR imaging in the evaluation of partial ureteral obstruction: An experimental study in the micropig

    SciTech Connect

    Thurnher, S.; Tzika, A.A.; Hricak, H.; Mattei, P.; Aboseif, S.; Engelstad, B.; Price, D.C. )

    1989-07-01

    Twelve Yucatan micropigs (3 controls; 3 sham-operated; 6 with unilateral obstruction) were studied to assess the value of noncontrast and contrast-enhanced (Gadolinium-DTPA) magnetic resonance (MR) imaging in the evaluation of partial ureteral obstruction. MR findings were correlated with findings of quantitative (Tc-99m-DMSA) scintigraphy, and histology. On noncontrast T1-weighted images, the normal porcine kidney demonstrated good corticomedullary contrast (CMC = 16.8% +/- 5.0). Five minutes after administration of Gd-DTPA, there was enhancement of the renal cortex (+24.4%) and medulla (+46.2%), and CMC was no longer discernible. Enhancement of the urine within the collecting system (+119.1%) was also observed. The obstructed kidneys demonstrated marked thinning of the renal parenchyma and decreased signal intensity on noncontrast T1- and T2-weighted images (P less than 0.01). Urine in the dilated collecting system did not differ significantly from urine in controls except in the three animals with urinary tract infection (P less than 0.05). Five minutes following injection of Gd-DTPA, there was enhancement of the renal parenchyma in all kidneys. Excretion was seen in three pigs and no excretion in two. Thus, useful information can be obtained in partial ureteral obstruction from both pre-contrast and Gd-DTPA-enhanced MR images of the kidney.

  20. Effects of a sunscreen formulation on albino hairless mice: a morphological approach.

    PubMed

    Hossy, Bryan Hudson; da Costa Leitão, Alvaro Augusto; Luz, Flávio Barbosa; dos Santos, Elisabete Pereira; Allodi, Silvana; de Pádula, Marcelo; de Oliveira Miguel, Nádia Campos

    2013-08-01

    The purpose of the study was to evaluate the effects of a sunscreen formulation on the skin of albino hairless mice subjected to simulated solar light (SSL) in terms of morphological changes. Young adult albino hairless mice HRS/J (n = 36) were used as an experimental model for determining skin photoaging changes. Mice were irradiated with SSL, and the sunscreen (estimated SPF 30, PF-UVA) was obtained from the Pharmacy College/UFRJ, Brazil. The animals were divided into four groups: non-treated (G1), radiation only (G2), sunscreen-treated (G3) and vehicle + radiation (G4). Animals from groups G2, G3 and G4 were irradiated weekly (5 weeks), with no immobilization. One week after the final exposure, the dorsal skin was observed using a dermatoscopic camera. Biopsies were analyzed in order to quantify neovascularization and to evaluate histological aspects of the skin. Neovascularization was also evaluated with immunohistochemical reactions for the Von Willebrand factor. Animals from G2 displayed classical morphological changes denoting skin photoaging: thickening of the epidermis, increased dermal cellularity, follicular keratosis, sebaceous gland hyperplasia, and angiogenesis. Animals from groups G3 and G1 displayed similar morphological profiles, without these changes. Animals from group G4 showed more morphological changes than group G2, emphasizing the relative importance of the putative photosensitizing components present in the vehicle formulation. The extent of the morphological skin changes suggested that the sunscreen formulation was effective against SSL, and showed the importance of assessing the phototoxicity of vehicle formulations.

  1. Hairless and the polyamine putrescine form a negative regulatory loop in the epidermis.

    PubMed

    Luke, Courtney T; Casta, Alexandre; Kim, Hyunmi; Christiano, Angela M

    2013-10-01

    Hairless (HR) is a nuclear protein with corepressor activity that is highly expressed in the skin and hair follicle. Mutations in Hairless lead to hair loss accompanied by the appearance of papules (atrichia with papular lesions), and similar phenotypes appear when the key polyamine enzymes ornithine decarboxylase (ODC) and spermidine/spermine N(1) -acetyltransferase (SSAT) are overexpressed. Both ODC and SSAT transgenic mice have elevated epidermal levels of putrescine, leading us to investigate the mechanistic link between putrescine and HR. We show here that HR and putrescine form a negative regulatory network, as epidermal ODC expression is elevated when HR is decreased and vice versa. We also show that the regulation of ODC by HR is dependent on the MYC superfamily of proteins, in particular MYC, MXI1 and MXD3. Furthermore, we found that elevated levels of putrescine lead to decreased HR expression, but that the SSAT-TG phenotype is distinct from that found when HR is mutated. Transcriptional microarray analysis of putrescine-treated primary human keratinocytes demonstrated differential regulation of genes involved in protein-protein interactions, nucleotide binding and transcription factor activity, suggesting that the putrescine-HR negative regulatory loop may have a large impact on epidermal homeostasis and hair follicle cycling.

  2. Hairless Streaks in Cattle Implicate TSR2 in Early Hair Follicle Formation

    PubMed Central

    Murgiano, Leonardo; Shirokova, Vera; Welle, Monika Maria; Jagannathan, Vidhya; Plattet, Philippe; Oevermann, Anna; Pienkowska-Schelling, Aldona; Gallo, Daniele; Gentile, Arcangelo; Mikkola, Marja; Drögemüller, Cord

    2015-01-01

    Four related cows showed hairless streaks on various parts of the body with no correlation to the pigmentation pattern. The stripes occurred in a consistent pattern resembling the lines of Blaschko. The non-syndromic hairlessness phenotype observed occurred across three generations of a single family and was compatible with an X-linked mode of inheritance. Linkage analysis and subsequent whole genome sequencing of one affected female identified two perfectly associated non-synonymous sequence variants in the critical interval on bovine chromosome X. Both variants occurred in complete linkage disequilibrium and were absent in more than 3900 controls. An ERCC6L missense mutation was predicted to cause an amino acid substitution of a non-conserved residue. Analysis in mice showed no specific Ercc6l expression pattern related to hair follicle development and therefore ERCC6L was not considered as causative gene. A point mutation at the 5'-splice junction of exon 5 of the TSR2, 20S rRNA accumulation, homolog (S. cerevisiae), gene led to the production of two mutant transcripts, both of which contain a frameshift and generate a premature stop codon predicted to truncate approximately 25% of the protein. Interestingly, in addition to the presence of both physiological TSR2 transcripts, the two mutant transcripts were predominantly detected in the hairless skin of the affected cows. Immunohistochemistry, using an antibody against the N-terminal part of the bovine protein demonstrated the specific expression of the TSR2 protein in the skin and the hair of the affected and the control cows as well as in bovine fetal skin and hair. The RNA hybridization in situ showed that Tsr2 was expressed in pre- and post-natal phases of hair follicle development in mice. Mammalian TSR2 proteins are highly conserved and are known to be broadly expressed, but their precise in vivo functions are poorly understood. Thus, by dissecting a naturally occurring mutation in a domestic animal

  3. Spent coffee ground extract suppresses ultraviolet B-induced photoaging in hairless mice.

    PubMed

    Choi, Hyeon-Son; Park, Eu Ddeum; Park, Yooheon; Suh, Hyung Joo

    2015-12-01

    The aim of this study is to evaluate the effect of spent coffee ground (SCG) ethanol extract on UVB-induced skin aging in hairless mice. An ethanol extract of SCG (ESCG) was prepared using the residue remaining after extraction of oil from roasted SCG. High performance liquid chromatography (HPLC) analysis showed that the content of caffeine (41.58 ± 0.54 μg/mg) was higher than that of chlorogenic acid isomers (~9.17 μg/mg) in ESCG. ESCG significantly decreased the UVB-induced intracellular reactive oxygen species in HaCaT cells. UVB-induced wrinkle formation in mice dorsal skin was effectively reduced by ESCG administration; high dose of ESCG (5 g/L) caused the reduction of wrinkle area by 30% compared with UVB-treated control (UVBC). This result correlated with the ESCG-mediated decrease in epidermis thickness (25%). In addition, ESCG administration significantly reduced transdermal water loss (20%) and erythema formation (35%) derived from UVB exposure. Collagen type I (COL-1) level in dorsal skin was effectively recovered by ESCG administration. These results were supported by down-regulation of collagen-degrading matrix metalloproteinase 2 (MMP2) and 9 (MMP9) expressions. Our results indicate that ESCG protects mouse skin from UVB-induced photoaging by suppressing the expression of matrix metalloproteinases. Our study suggests that ESCG may be anti-photoaging agent.

  4. Garlic Supplementation Ameliorates UV-Induced Photoaging in Hairless Mice by Regulating Antioxidative Activity and MMPs Expression.

    PubMed

    Kim, Hye Kyung

    2016-01-08

    UV exposure is associated with oxidative stress and is the primary factor in skin photoaging. UV-induced reactive oxygen species (ROS) cause the up-regulation of metalloproteinase (MMPs) and the degradation of dermal collagen and elastic fibers. Garlic and its components have been reported to exert antioxidative effects. The present study investigated the protective effect of garlic on UV-induced photoaging and MMPs regulation in hairless mice. Garlic was supplemented in the diet, and Skh-1 hairless mice were exposed to UV irradiation five days/week for eight weeks. Mice were divided into four groups; Non-UV, UV-irradiated control, UV+1% garlic powder diet group, and UV+2% garlic powder diet group. Chronic UV irradiation induced rough wrinkling of the skin with hyperkeratosis, and administration of garlic diminished the coarse wrinkle formation. UV-induced dorsal skin and epidermal thickness were also ameliorated by garlic supplementation. ROS generation, skin and serum malondialdehyde levels were significantly increased by UV exposure and were ameliorated by garlic administration although the effects were not dose-dependent. Antioxidant enzymes such as superoxide dismutase and catalase activities in skin tissues were markedly reduced by UV irradiation and garlic treatment increased these enzyme activities. UV-induced MMP-1 and MMP-2 protein levels were suppressed by garlic administration. Furthermore, garlic supplementation prevented the UV-induced increase of MMP-1 mRNA expression and the UV-induced decrease of procollagen mRNA expression. These results suggest that garlic may be effective for preventing skin photoaging accelerated by UV irradiation through the antioxidative system and MMP regulation.

  5. Effect of thermodynamic activity on skin permeation and skin concentration of triamcinolone acetonide.

    PubMed

    Ishii, Hiroshi; Todo, Hiroaki; Sugibayashi, Kenji

    2010-04-01

    Effects of thermodynamic activity and the state (solution/suspension) of triamcinolone acetonide (TA) on skin permeation and concentration were physicochemically and kinetically analyzed. Permeation of TA through a silicone membrane, hairless rat skin (full-thickness skin or stripped skin) or a three-dimensional cultured human skin model (LSE-high) was determined and a permeability coefficient (P), partition coefficient (K) , diffusion coefficient (D) and steady-state flux (J) were calculated. The resulting J values proportionally increased with an increase in the TA activity in the drug solution and similar P, K and D values were obtained independent of the TA state (solution/suspension) in all membranes except for full-thickness hairless rat skin. On the other hand, the TA permeation through full-thickness hairless rat skin with the 1000 microg/ml suspension was higher than that expected judging by the thermodynamic acidity of TA. Higher D and P values were also obtained in the skin permeation of TA from the 1000 microg/ml suspension. Morphological observation of the skin surface by scanning electron microscope (SEM) showed the presence of TA solids in the hair follicles after application of the TA suspension. These results suggest that dissolved TA may be permeated predominantly through the stratum corneum, but that solid TA may be passed through the hair follicles to enter the dermis. The present physicochemical and kinetic analysis provides useful information to develop topical steroid formulations.

  6. Effect of electrospun non-woven mats of dibutyryl chitin/poly(lactic acid) blends on wound healing in hairless mice.

    PubMed

    Jang, Seon Il; Mok, Ji Ye; Jeon, In Hwa; Park, Kwang-Hyun; Nguyen, Thuy Thi Thu; Park, Jun Seo; Hwang, Hee Min; Song, Mi-Sun; Lee, Duckhee; Chai, Kyu Yun

    2012-03-09

    The aim of this study was to examine the proliferative ability of dibutyryl chitin (DBC) on scratch wounds in HaCaT keratinocytes and to evaluate the effect of nanoporous non-woven mat (DBCNFM) on skin wound healing in hairless mice using the advantages of DBCNFM, such as high porosity and high surface area to volume. The cell spreading activity of DBC was verified through a cell spreading assay in scratched human HaCaT keratinocytes. Scratch wound experiments showed that DBC notably accelerates the spreading rate of HaCaT keratinocytes in a dose dependent manner. The molecular aspects of the healing process were also investigated by hematoxylin & eosin staining of the healed skin, displaying the degrees of reepithelialization and immunostaining on extracellular matrix synthesis and remodeling of the skin. Topical application of DBCNFM significantly reduced skin wound rank scores and increased the skin remodeling of the wounded hairless mice in a dose dependent way. Furthermore, DBCNFM notably increased the expression of the type 1 collagen and filaggrin. These results demonstrate that DBC efficiently accelerates the proliferation of HaCaT keratinocytes and DBCNFM notably increases extracellular matrix synthesis on remodeling of the skin, and these materials are a good candidate for further evaluation as an effective wound healing agent.

  7. Identification of free and esterified hydroxyoctadecadienoates (HODEs) and linoleate-hydroxylating pathway in the epidermis of hairless mice.

    PubMed

    Inokuchi, T; Hidaka, T; Noda, Y; Nishi, J; Kotegawa, M; Ogura, R

    1992-01-01

    Epidermal homogenates of hairless mice contained a large amount of lipid material showing a single peak on reverse phase (RP)-high pressure liquid chromatography (HPLC) with a maximum absorbance of 234 nm, which was different in retention time from arachidonate metabolites such as 12-HETE, 15-HETE and 5-HETE. The production of this material was dependent on exogenous linoleate concentration, protein concentration and buffer pH. This material was identified to be a mixture of 13-HODE and 9-HODE on the basis of UV absorbance spectra, retention times on RP-HPLC, straight phase (SP)-HPLC, gas chromatography-mass spectrometry (GC/MS) and mass spectra obtained. As assessed by SP-HPLC after saponification, these two HODEs were found to exist primarily in esterified forms in the skin. Neither substance was produced following heat denaturation of the homogenate. These results indicate that 13- and 9-HODEs are produced from linoleate enzymatically at physiologically relevant levels in the epidermis of hairless mice. Thus, it is possible that these two materials may play some important role in pathophysiology of the skin.

  8. Delayed induction of pigmented spots on UVB-irradiated hairless mice.

    PubMed

    Naganumaa, M; Yagi, E; Fukuda, M

    2001-01-01

    Human skin exposed to solar radiation for a long time subsequently develops pigmented spots, which are named solar lentigines. Since no animal model of this process is currently available, we attempted to induce similar spots in pigmented hairless mice. The mice were irradiated at 38 or 94 mJ/cm(2) three times/week for various periods of time (1-8 weeks) under an ultraviolet light source (Toshiba FL-SE; UVB). Skin pigmentation of irradiated mice was visually observed and skin color was determined with a colorimeter for 78 weeks. Uniform pigmentation was induced, but persisted only during exposure, disappearing completely within 2 weeks after cessation of exposure. At about 28 weeks after the first exposure, pigmented spots suddenly began to appear. These pigmented spots were less than 2 mm in diameter and light brown in color. The length of the latent period until appearance and the extent of development of these spots were dependent on the exposure period. Histological examination revealed increased numbers of active melanocytes and melanin granules in the affected epidermis. These pigmented spots closely resemble solar lentigines in humans, and the mice should be useful as an animal model of solar lentigines.

  9. Cutaneous Injury-Related Structural Changes and Their Progression following Topical Nitrogen Mustard Exposure in Hairless and Haired Mice

    PubMed Central

    Orlicky, David J.; White, Carl W.; Agarwal, Rajesh

    2014-01-01

    To identify effective therapies against sulfur mustard (SM)-induced skin injuries, various animals have been used to assess the cutaneous pathology and related histopathological changes of SM injuries. However, these efforts to establish relevant skin injury endpoints for efficacy studies have been limited mainly due to the restricted assess of SM. Therefore, we employed the SM analog nitrogen mustard (NM), a primary vesicating and bifunctional alkylating agent, to establish relevant endpoints for efficient efficacy studies. Our published studies show that NM (3.2 mg) exposure for 12–120 h in both the hairless SKH-1 and haired C57BL/6 mice caused clinical sequelae of toxicity similar to SM exposure in humans. The NM-induced cutaneous pathology-related structural changes were further analyzed in this study and quantified morphometrically (as percent length or area of epidermis or dermis) of skin sections in mice showing these lesions. H&E stained skin sections of both hairless and haired mice showed that NM (12–120 h) exposure caused epidermal histopathological effects such as increased epidermal thickness, epidermal-dermal separation, necrotic/dead epidermis, epidermal denuding, scab formation, parakeratosis (24–120 h), hyperkeratosis (12–120 h), and acanthosis with hyperplasia (72–120 h). Similar NM exposure in both mice caused dermal changes including necrosis, edema, increase in inflammatory cells, and red blood cell extravasation. These NM-induced cutaneous histopathological features are comparable to the reported lesions from SM exposure in humans and animal models. This study advocates the usefulness of these histopathological parameters observed due to NM exposure in screening and optimization of rescue therapies against NM and SM skin injuries. PMID:24416404

  10. Cutaneous injury-related structural changes and their progression following topical nitrogen mustard exposure in hairless and haired mice.

    PubMed

    Tewari-Singh, Neera; Jain, Anil K; Orlicky, David J; White, Carl W; Agarwal, Rajesh

    2014-01-01

    To identify effective therapies against sulfur mustard (SM)-induced skin injuries, various animals have been used to assess the cutaneous pathology and related histopathological changes of SM injuries. However, these efforts to establish relevant skin injury endpoints for efficacy studies have been limited mainly due to the restricted assess of SM. Therefore, we employed the SM analog nitrogen mustard (NM), a primary vesicating and bifunctional alkylating agent, to establish relevant endpoints for efficient efficacy studies. Our published studies show that NM (3.2 mg) exposure for 12-120 h in both the hairless SKH-1 and haired C57BL/6 mice caused clinical sequelae of toxicity similar to SM exposure in humans. The NM-induced cutaneous pathology-related structural changes were further analyzed in this study and quantified morphometrically (as percent length or area of epidermis or dermis) of skin sections in mice showing these lesions. H&E stained skin sections of both hairless and haired mice showed that NM (12-120 h) exposure caused epidermal histopathological effects such as increased epidermal thickness, epidermal-dermal separation, necrotic/dead epidermis, epidermal denuding, scab formation, parakeratosis (24-120 h), hyperkeratosis (12-120 h), and acanthosis with hyperplasia (72-120 h). Similar NM exposure in both mice caused dermal changes including necrosis, edema, increase in inflammatory cells, and red blood cell extravasation. These NM-induced cutaneous histopathological features are comparable to the reported lesions from SM exposure in humans and animal models. This study advocates the usefulness of these histopathological parameters observed due to NM exposure in screening and optimization of rescue therapies against NM and SM skin injuries.

  11. Effect of infrared radiation A on photoaged hairless mice harboring eumelanin and pheomelanin in the epidermis.

    PubMed

    Okazaki, Shizuka; Funasaka, Yoko; Wakamatsu, Kazumasa; Kawana, Seiji; Saeki, Hidehisa

    2015-04-01

    Infrared radiation A (IRA) is absorbed by melanin and generates heat. Therefore, the effect of IRA could be well analyzed using skin, which contains melanin in the epidermis. Hairless mice harboring epidermal melanocytes that produce eumelanin, pheomelanin, or non-melanin were generated by backcrossing K14-stem cell factor mice, recessive yellow mice, and then albino hairless mice. High-dose IRA was irradiated over 18 weeks after the establishment of photoaged mice by irradiation with ultraviolet B (UVB) three times a week for 14 weeks. Tumor formation was assessed every week. The formation of cyclobutane pyrimidine dimer and apoptotic cells by the irradiation of IRA and UVB was evaluated. Repetitive irradiation of IRA did not promote tumor formation in all types of mice. Pre-irradiation of IRA to UVB, but not post-irradiation, accelerated the elimination of cyclobutane pyrimidine dimers and enhanced apoptosis; these effects were most obvious in eumelanin-producing mice. Real-time polymerase chain reaction analysis showed downregulation of FLICE (cellular caspase 8)-like inhibitory protein and B-cell lymphoma-extra large and upregulation of Bcl-2-associated X protein by UVB, but further enhancement of these molecules by pre-irradiation of IRA was not observed. These results indicate that IRA does not confer the promotion of UVB-induced carcinogenesis in photoaged mice harboring epidermal melanocytes and that photochemical reaction between IRA and melanin might be involved in the induction of apoptosis and the elimination of cyclobutane pyrimidine dimers by UVB. The enhancement of apoptosis by pre-irradiation of IRA to UVB might be induced by mechanisms other than the modification of the mRNA expression of FLICE (cellular caspase 8)-like inhibitory protein, B-cell lymphoma-extra large, and Bcl-2-associated X.

  12. Mutations in the hairless gene underlie APL in three families of Pakistani origin

    PubMed Central

    Kraemer, Liv; Wajid, Muhammad; Shimomura, Yutaka; Christiano, Angela M.

    2009-01-01

    Summary Background Atrichia with papular lesions (APL) (OMIM#209500) is a rare autosomal recessively inherited form of irreversible alopecia characterized by papular lesions of keratin-filled cysts on various regions of the body. Males and females are equally affected and present with a distinct pattern of total hair loss on scalp, axilla and body. It begins shortly after birth with the development of hair loss, and patients are normally devoid of eyelashes and eyebrows. Mutations in the hairless (HR) gene have been previously shown to be responsible for APL. Objective In this study, we studied the molecular basis of APL in three unrelated families of Pakistani origin. Method Molecular analysis of the HR genes was performed on genomic DNA from probands and family members. Results DNA sequencing of the HR gene in family A revealed a novel homozygous 2 bp deletion in exon 6 leading to a frameshift and a downstream premature termination codon in exon 8 (1782-83delAG). In family B, we identified a novel homozygous deletion of a G nucleotide at the exon 15–intron 15 boundary, termed 3097delG. Family C carries a previously reported missense mutation consisting of an A-to-G transition at nucleotide 276 resulting in the mutation N970S in exon 14. Conclusion Two mutations identified in this study are novel mutations in the HR gene and extend the body of evidence implicating the hairless gene family in the pathogenesis of human skin disorders. The one previously reported mutation suggests it may represent a recurrent mutation, or alternatively, an allele that is widely dispersed around the world. PMID:18164595

  13. Topical formulations containing finasteride. Part I: in vitro permeation/penetration study and in vivo pharmacokinetics in hairless rat.

    PubMed

    Monti, Daniela; Tampucci, Silvia; Burgalassi, Susi; Chetoni, Patrizia; Lenzi, Carla; Pirone, Andrea; Mailland, Federico

    2014-08-01

    In hair follicle (Hf) cells, the type-2 5-α-reductase enzyme, implicated in androgenetic alopecia, is selectively inhibited by finasteride (FNS). Because an effective topical formulation to deliver FNS to Hf is currently unavailable, this investigation aimed at evaluating in vitro FNS skin permeation and retention through and into hairless rat and human abdominal skin. Four hydroxypropyl chitosan (HPCH)-based formulations (P-08-012, P-08-016, P-08-063, and P-08-064) and one anhydrous formulation without HPCH (P-10-008) were tested. The pharmacokinetics in plasma and skin after application of P-08-016 or P-10-008 on dorsal rat skin with single and repeated doses was investigated. P-08-016 performed the best in driving FNS to the reticular dermis without producing a high transdermal flux. Neither the in vivo single nor the repeated dose experiments produced plasma levels of FNS and no differences were found between formulations concerning skin retention. No increase in the amount of drug retained in the skin was obtained with the repeated dose experiment. In conclusion, the HPCH-based formulation P-08-016 might represent an alternative to systemic therapy for its ability to promote a cutaneous depot of FNS in the region of hair bulbs, minimizing systemic absorption even after repeated treatments.

  14. Latent Herpes Simplex Virus Infections in Sensory Ganglia of Hairless Mice Prevented by Acycloguanosine†

    PubMed Central

    Klein, Richard J.; Friedman-Kien, Alvin E.; DeStefano, Eugene

    1979-01-01

    Acycloguanosine (ACG) was able to prevent the fatal outcome of herpes simplex virus-induced skin infections of the lumbosacral or orofacila area in hairless mice. Topical ACG treatment was more effective than systemic treatment in preventing the evolution of skin lesions. Acute ganglionic infections in the trigeminal ganglia were prevented by ACG, and latent ganglionic infections did not become established when the ACG treatment was initiated 3 h after infection. Serum antibody titers were, on the average, eight times higher in mice which developed latent ganglionic infections after ACG treatment than in mice without evidence of herpes simplex virus latency in ganglia. Reinoculation of ACG-treated mice at a site different from that of the primary inoculation did not lead to the establishment of a second latent infection with the homologous virus type when a latent infection was already present. In mice without evidence of latent infection after the primary inoculation, a latent infection at the site of reinoculation became established in 25% of the animals. PMID:230784

  15. Enhanced efficacy of cidofovir combined with vaccinia immune globulin in treating progressive cutaneous vaccinia virus infections in immunosuppressed hairless mice.

    PubMed

    Smee, Donald F; Dagley, Ashley; Downs, Brittney; Hagloch, Joseph; Tarbet, E Bart

    2015-01-01

    The treatment of progressive vaccinia in individuals has involved antiviral drugs, such as cidofovir (CDV), brincidofovir, and/or tecovirimat, combined with vaccinia immune globulin (VIG). VIG is costly, and its supply is limited, so sparing the use of VIG during treatment is an important objective. VIG sparing was modeled in immunosuppressed mice by maximizing the treatment benefits of CDV combined with VIG to determine the effective treatments that delayed the time to death, reduced cutaneous lesion severity, and/or decreased tissue viral titers. SKH-1 hairless mice immunosuppressed with cyclophosphamide and hairless SCID mice (SHO strain) were infected cutaneously with vaccinia virus. Monotherapy, dual combinations (CDV plus VIG), or triple therapy (topical CDV, parenteral CDV, and VIG) were initiated 2 days postinfection and were given every 3 to 4 days through day 11. The efficacy assessment included survival rate, cutaneous lesion severity, and viral titers. Delays in the time to death and the reduction in lesion severity occurred in the following order of efficacy: triple therapy had greater efficacy than double combinations (CDV plus VIG or topical plus parenteral CDV), which had greater efficacy than VIG alone. Parenteral administration of CDV or VIG was necessary to suppress virus titers in internal organs (liver, lung, and spleen). The skin viral titers were significantly reduced by triple therapy only. The greatest efficacy was achieved by triple therapy. In humans, this regimen should translate to a faster cure rate, thus sparing the amount of VIG used for treatment.

  16. Inhibition of acyl-CoA cholesterol O-acyltransferase reduces the cholesteryl ester enrichment of atherosclerotic lesions in the Yucatan micropig.

    PubMed

    Bocan, T M; Mueller, S B; Uhlendorf, P D; Brown, E Q; Mazur, M J; Black, A E

    1993-03-01

    Atherosclerotic lesion development may be altered indirectly by regulating plasma cholesterol or directly by inhibition of acyl-CoA cholesterol O-acyltransferase (ACAT) within cells of the artery. Yucatan micropigs were meal-fed a 2% cholesterol, 8% peanut oil, 8% coconut oil purified diet for 1 month prior to administration of the potent, bioavailable ACAT inhibitor CI-976, and induction of atherosclerotic lesions by chronic endothelial damage. After 84-108 days of therapy, CI-976 decreased mean plasma VLDL-cholesterol 85-91% and cumulative VLDL-exposure (area under VLDL-time curve) by 65%. However, overall plasma total, LDL and HDL cholesterol and triglyceride levels were unchanged. CI-976 decreased liver cholesteryl ester (CE) content 65% without significantly affecting adrenal CE content. The CE content of the injured left femoral, left iliac and abdominal aorta and uninjured right femoral and iliac arteries and thoracic aorta was reduced 62-78% by CI-976. Systemic plasma CI-976 levels measured 24 h post-dose ranged from 2.26 to 4.05 micrograms/ml and significantly correlated with the reduction in both VLDL and vessel CE content. Thus, we conclude that inhibition of ACAT can blunt the cholesteryl ester enrichment of developing atherosclerotic lesions by preventing reesterification and storage of lipoprotein cholesterol within vascular cells and by reducing the plasma level and delivery to the arterial wall of such atherogenic lipoproteins as VLDL.

  17. Dietary deficiencies of unsaturated fatty acids and starch cause atopic dermatitis-like pruritus in hairless mice.

    PubMed

    Fujii, Masanori; Shimazaki, Yuki; Muto, Yoshiko; Kohno, Shigekatsu; Ohya, Susumu; Nabe, Takeshi

    2015-02-01

    Hairless mice fed with a special diet (named HR-AD) show atopic dermatitis (AD)-like pruritic skin inflammation that is almost completely resolved with the supplementation of an unsaturated fatty acid (UFA), the linoleic acid (LA). This suggests that the dietary deficiency of LA is the key cause of this dermatitis. However, because there is no appropriate control diet for HR-AD, the involvement of other dietary ingredients cannot be ruled out. Furthermore, it has not yet been tested whether only UFA deficiency can cause such AD-like pruritus. In this study, using semi-purified custom diets, we attempted to reproduce this syndrome. Four-week-old hairless mice were maintained on a widely used standard diet American Institute of Nutrition-76A (AIN-76A), its modifications, or HR-AD. Several modifications of fat and carbohydrate components revealed that dietary deficiency of both UFAs and cornstarch was required to induce severe skin barrier dysfunction as typically occurred in HR-AD-fed mice. An UFA- and cornstarch-deficient diet caused severe AD-like pruritus comparable to HR-AD, despite weak Th2 immune responses and absence of immunoglobulin E production. On the other hand, a diet lacking UFAs but containing cornstarch significantly alleviated the development of pruritic dermatitis. Furthermore, the supplementation of wheat starch similarly improved skin barrier function. In conclusion, this study showed that a lack of certain starches might also be the cause of diet-induced AD. Our findings could help to reproduce the diet-induced AD itch model and also provide evidence that certain starches can have protective and ameliorative effects on AD-like pruritus.

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

    SciTech Connect

    Kao, J.; Hall, J.; Helman, G.

    1988-06-15

    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.

  19. (Z)-5-(2,4-Dihydroxybenzylidene)thiazolidine-2,4-dione Prevents UVB-Induced Melanogenesis and Wrinkle Formation through Suppressing Oxidative Stress in HRM-2 Hairless Mice

    PubMed Central

    Lee, Bonggi; Moon, Kyoung Mi; Kim, Seong Jin; Kim, So Hee; Kim, Dae Hyun; An, Hye Jin; Jeong, Ji Won; Kim, Ye Ra; Son, Sujin; Kim, Min Jo; Chung, Ki Wung; Lee, Eun Kyeong; Chun, Pusoon; Ha, Young Mi; Kim, Min-Sun; Mo, Sang Hyun; Moon, Hyung Ryong; Chung, Hae Young

    2016-01-01

    Background. Uncontrolled melanogenesis and wrinkle formation are an indication of photoaging. Our previous studies demonstrated that (Z)-5-(2,4-dihydroxybenzylidene)thiazolidine-2,4-dione (MHY498) inhibited tyrosinase activity and melanogenesis in vitro. Objective. To examine in vivo effects of MHY498 as an antiaging compound on UVB-induced melanogenesis and wrinkle formation, we topically applied MHY498 on dorsal skin of HRM-2 hairless mice. Methods. Using histological analysis, we evaluated effects of MHY498 on melanogenesis and wrinkle formation after UVB exposure. In addition, related molecular signaling pathways were examined using western blotting, fluorometric assay, and enzyme-linked immunosorbent assay. Results. MHY498 suppressed UVB-induced melanogenesis by inhibiting phosphorylation of CREB and translocation of MITF protein into the nucleus, which are key factors for tyrosinase expression. Consistently, tyrosinase protein levels were notably reduced in the dorsal skin of the hairless mice by MHY498 treatment. Furthermore, MHY498 inhibited UVB-induced wrinkle formation and collagen fiber destruction by increasing type 1 procollagen concentration and decreasing protein expression levels of MMPs, which play an essential role in collagen fiber degradation. As a mechanism, MHY498 notably ameliorated UVB-induced oxidative stress and NF-κB activation in the dermal skin of the hairless mice. Conclusion. Our study suggests that MHY498 can be used as a therapeutic or cosmetic agent for preventing uncontrolled melanogenesis and wrinkle formation. PMID:27242917

  20. Prevention of ultraviolet damage to the dermis of hairless mice by sunscreens

    SciTech Connect

    Kligman, L.H.; Akin, F.J.; Kligman, A.M.

    1982-02-01

    To assess the ability of sunscreens to protect connective tissue from actinic damage, hairless mice were irradiated with Westinghouse FS20 sunlamps thrice weekly for 30 weeks. Each exposure, consisting mainly of UV-B and the less energetic UV-A, was approximately 6 human minimal erythema doses under these lights. One group of animals received irradiation only. The other 2 groups were treated, prior to irradiation, with sunscreens of either low or high sun protection factors (SPF 2 and SPF 15, respectively). Skin biopsies were taken at 10-week intervals and were stained with various histochemical stains to reveal changes in the dermis. The unprotected, irradiated animals showed a great increase in the following: reticulin fibers, elastic fibers to the extent of elastosis, neutral and acid mucopolysaccharides and melanin production. The SPF 15 sunscreen completely prevented these changes. The SPF 2 sunscreen was less effective. These effects were substantiated by ultrastructural examination of the tissues by electron microscopy. A surprising histologic finding was the repair capability of the dermis in the post-irradiation period.

  1. In vivo optical coherence tomography of percutaneous implants in hairless mice

    NASA Astrophysics Data System (ADS)

    Donner, S.; Witte, F.; Bartsch, I.; Petraglia, F.; Massow, O.; Heidrich, M.; Lubatschowski, H.; Heisterkamp, A.; Krüger, A.

    2010-02-01

    Biocompatibility studies of percutanous implants in animal models usually involve numerous lethal biopsies for subsequent morphometric analysis of the implant-tissue interface. A common drawback of the study protocol is the restriction of the analysis to one final time point. In this study optical coherence tomography (OCT) was used to visualize and enable quantification of the local skin anatomy in the vicinity of a percutaneous implant in an animal model using hairless mice. Non invasive in vivo optical biopsies were taken on predetermined time points after implantation and ex vivo in situ at the day of noticeable inflammation. The custom made Fourier-domain OCT system was programmed for imaging with different scanning schemes. A spoke-pattern of 72 cross-sectional scans which was centred at the midpoint of the circular shaped implants was acquired and worked best for the in-vivo situation. Motion-artefact-free three-dimensional tomograms were obtained from the implant site before excision and preparation for histology. Morphometric parameters such as epithelial downgrowth, distance to normal growth and tissue thickness were extracted from the images with a simple segmentation algorithm. Qualitatively, the OCT B-Scans are in good agreement with histological sections. Therefore, OCT can provide additional valuable information about the implant-tissue interface at freely selectable time points before the lethal biopsy. Locally confined quantitative assessments of tissue-implant interaction for in vivo postoperative monitoring can be carried out.

  2. Agents that cause enlargement of sebaceous glands in hairless mice. II. Ultraviolet radiation.

    PubMed

    Lesnik, R H; Kligman, L H; Kligman, A M

    1992-01-01

    We have developed a murine model to measure the effects on sebaceous glands of ultraviolet (UV) radiation. Hairless mice were irradiated with Westinghouse FS-40 tubes filtered to attenuate the radiation below 290 nm. Emission was mainly in the UVB range (peak, 313nm). Single and multiple exposures were given with fractions or multiples of one minimal erythemal dose (MED). Biopsies, fixed for light microscopy, were stained with H & E. Under high power, sebocytes of 30 glands per specimen were counted and the means determined. A single exposure of 1 MED caused a significant increase in sebocyte count, as did thrice-weekly exposures to 0.5 MED for 3 weeks. One 3-MED exposure produced sebocyte necrosis, yet 30 exposures at 4 MED failed to ablate the glands. In both cases there was rebound enlargement which had not returned to control levels by the end of the studies (24-30 weeks). Prolonged irradiation produced maximum enlargement in a few weeks. Thus, in a manner similar to other skin components, the response of sebaceous glands to UV radiation is one of hyperplasia.

  3. Repeated Treatments with Ingenol Mebutate Prevents Progression of UV-Induced Photodamage in Hairless Mice

    PubMed Central

    Thaysen-Petersen, Daniel; Bay, Christiane; Hald, Andreas; Skak, Kresten; Zibert, John Robert; Paasch, Uwe; Wulf, Hans Christian; Haedersdal, Merete

    2016-01-01

    Background and Aim Ingenol mebutate (IngMeb) is an effective treatment for actinic keratosis. In this study, we hypothesized that repeated treatments with IngMeb may prevent progression of UV-induced photodamage, and that concurrent application of a corticosteroid may reduce IngMeb-induced local skin responses (LSR). Methods Hairless mice (n = 60; 3 groups of 20 mice) were irradiated with solar simulated ultraviolet radiation (UVR) throughout the study. Five single treatments with IngMeb were given at 4-week intervals (Days 21, 49, 77, 105, and 133). Clobetasol propionate (CP) was applied once daily for 5 days prior to each IngMeb application, as well as 6 h and 1 day post treatment. One week after IngMeb treatment No. 1, 3, and 5 (Days 28, 84, and 140), biopsies from four mice in each group were collected for histological evaluation of UV-damage on a standardized UV-damage scale (0–12). LSR (0–24) were assessed once daily (Days 1–7) after each IngMeb treatment. Results IngMeb prevented progression of photodamage in terms of keratosis grade, epidermal hypertrophy, dysplasia, and dermal actinic damage with a lower composite UV-damage score on day 140 (UVR 10.25 vs. UVR+IngMeb 6.00, p = 0.002) compared to UVR alone. IngMeb induced LSR, including erythema, flaking, crusting, bleeding, vesiculation, and ulceration. Concurrent CP increased LSR (max LSR Tx 1–5: UVR+IngMeb+CP 3.6–5.5 vs. UVR+IngMeb 2.6–4.3) and provided better prevention of photodamage compared to IngMeb alone (Day 140: UVR+IngMeb 6.00 vs. UVR+IngMeb+CP 3.00 p < 0.001). Conclusion Repeated field-directed treatments with IngMeb prevent progression of cutaneous photodamage in hairless mice, while CP cannot be used to alleviate IngMeb-induced LSR. The findings suggest that IngMeb may potentially serve as a prophylactic treatment for UV-induced tumors. PMID:27636884

  4. Programmable transdermal delivery of nicotine in hairless guinea pigs using carbon nanotube membrane pumps.

    PubMed

    Paudel, Kalpana S; Wu, Ji; Hinds, Bruce J; Stinchcomb, Audra L

    2012-10-01

    A compact switchable transdermal nicotine patch device was demonstrated to be effective in vivo in a hairless guinea pig animal model. This required the development and validation of a quantitative method for the simultaneous determination of cotinine and nicotine in hairless guinea pig plasma by liquid chromatography-mass spectrometry. Nicotine metabolism in hairless guinea pigs is rapid and cotinine was found to be the viable nicotine marker. The portable carbon nanotube membrane device, powered by a 1.5 V watch battery, was demonstrated to be a power efficient method to pump nicotine at levels six to eight times that of passive diffusion. Cotinine blood plasma levels in hairless guinea pigs were seen to increase from 6 to 12 ng/mL when the patch was turned from passive diffusion to an active pumping state. These nicotine patch devices are highly promising for potential clinical applications, with programmed delivery based on remote counseling, in order to improve smoking cessation treatments.

  5. Lgr5+ stem cells and their progeny in mouse epidermis under regimens of exogenous skin carcinogenesis, and their absence in ensuing skin tumors

    PubMed Central

    van de Glind, Gerline C.; Out, Jacoba J.; Rebel, Heggert G.; Tensen, Cornelis P.; de Gruijl, Frank R.

    2016-01-01

    Actively proliferating Lgr5+ skin stem cells are found deep in the hair follicle (HF). These cells renew the HF and drive its expansion in anagen phase. Their long residence and continuous mitotic activity make them prime candidates to transform into skin tumor-initiating cells. This was investigated by subjecting Lgr5-EGFP-Ires-CreERT2/R26R-LacZ mice (haired and hairless) to chemical and UV carcinogenic regimens. In the course of these regimens Lgr5+ cells (EGFP+) remained exclusively located in HFs, and in deep-seated cysts of hairless skin. In haired mice, progeny of Lgr5+ stem cells (LacZ+ after a pulse of tamoxifen) appeared in the interfollicular epidermis upon UV-induced sunburn and in TPA-induced hyperplasia. In hairless mice the progeny remained located in deep-seated cysts and in HF remnants. Progeny in hairless skin was only detected interfollicularly at a late stage, in between outgrowing tumors. Lgr5+ stem cells were absent in the ultimate tumor masses, and no tumor appeared to be a (clonal) expansion of Lgr5+ cells (52 tumors with tamoxifen at the start of carcinogenesis, 42 tumors with tamoxifen late during tumor outgrowth). In contrast to CD34/K15+ quiescent bulge stem cells, actively proliferating Lgr5+ stem cells do therefore not appear to be tumor drivers in experimental skin carcinogenesis. PMID:27409834

  6. Hematology and clinical chemistry values of normal and euthymic hairless adult male Dunkin-Hartley guinea pigs (Cavia porcellus).

    PubMed

    Waner, Trevor; Avidar, Yaakov; Peh, Hao-Chang; Zass, Rosa; Bogin, Eitan

    1996-01-01

    Hematology and serum chemistry measurements were performed on blood specimens from 12 male Dunkin-Hartley hairless guinea pigs Crl:IAF(HA)BR and 10 haired Dunkin-Hartley male guinea pigs Crl:(HA)BR. Significantly higher activities of alanine aminotransferase, aspartate aminotransferase, amylase, and creatine kinase were observed in the hairless guinea pigs as compared to the haired strain. Alkaline phosphatase activity was found to be lower in the hairless guinea pig. The hairless guinea pigs were found to have serum urea concentrations approximately 46% higher than the normal guinea pig strain. The erythrocytic mean cell volume of the hairless strain was found to be smaller, with a greater hemoglobin content. Hairless guinea pigs were found to have approximately 40% fewer leukocytes with a reversed lymphocyte:neutrophil ratio compared to the haired guinea pigs which had much higher lymphocyte counts.

  7. Temperature Preference in IAF Hairless and Hartley Guinea Pigs (Cavia porcellus).

    PubMed

    Kleven, Gale A; Joshi, Prianca

    2016-03-01

    The Hairless strain of guinea pigs (Cavia porcellus) is the result of a spontaneous recessive mutation first identified at the Institute Armand Frappier (IAF) in 1978. Despite the longstanding availability of this strain, little is known about its thermoregulatory behavior. The aim of this study was to determine temperature preference in Hartley and Hairless guinea pigs by observing each strain in a ring-shaped apparatus containing a nonlinear temperature gradient. Temperatures were maintained by separately controlled heating mats lining the apparatus. Set point temperatures ranged from 24 to 38 °C. Guinea pigs (Hartley female, Hairless female, and Hairless male guinea pigs; n = 8 each group) were placed either singly or in pairs at 1 of the 8 randomized starting points within the apparatus. Subjects were observed for 30 min and coded for location within the temperature gradient by both frequency and duration. When placed singly in the apparatus, all 3 groups spent more time in the 30 °C zones. However, when placed as pairs with a cagemate, Hartley female guinea pigs spent more time in the cooler range of temperatures from 24 to 30 °C, whereas Hairless guinea pigs preferred a range of 30 to 38 °C. These results confirm a temperature preference of 30 ± 2 °C for both Hartley and Hairless guinea pigs when singly housed. However, data from the paired housing condition suggest that context plays an important role in thermoregulatory behavior.

  8. Temperature Preference in IAF Hairless and Hartley Guinea Pigs (Cavia porcellus)

    PubMed Central

    Kleven, Gale A; Joshi, Prianca

    2016-01-01

    The Hairless strain of guinea pigs (Cavia porcellus) is the result of a spontaneous recessive mutation first identified at the Institute Armand Frappier (IAF) in 1978. Despite the longstanding availability of this strain, little is known about its thermoregulatory behavior. The aim of this study was to determine temperature preference in Hartley and Hairless guinea pigs by observing each strain in a ring-shaped apparatus containing a nonlinear temperature gradient. Temperatures were maintained by separately controlled heating mats lining the apparatus. Set point temperatures ranged from 24 to 38 °C. Guinea pigs (Hartley female, Hairless female, and Hairless male guinea pigs; n = 8 each group) were placed either singly or in pairs at 1 of the 8 randomized starting points within the apparatus. Subjects were observed for 30 min and coded for location within the temperature gradient by both frequency and duration. When placed singly in the apparatus, all 3 groups spent more time in the 30 °C zones. However, when placed as pairs with a cagemate, Hartley female guinea pigs spent more time in the cooler range of temperatures from 24 to 30 °C, whereas Hairless guinea pigs preferred a range of 30 to 38 °C. These results confirm a temperature preference of 30 ± 2 °C for both Hartley and Hairless guinea pigs when singly housed. However, data from the paired housing condition suggest that context plays an important role in thermoregulatory behavior. PMID:27025807

  9. Anti-photoaging properties of the phosphodiesterase 3 inhibitor cilostazol in ultraviolet B-irradiated hairless mice

    PubMed Central

    Kim, Ha Neui; Gil, Chan Hee; Kim, Yu Ri; Shin, Hwa Kyoung; Choi, Byung Tae

    2016-01-01

    We investigated whether cilostazol, an activator of cyclic adenosine monophosphate (cAMP)-dependent intracellular signaling, could inhibit ultraviolet B (UVB) irradiation-induced photoaging in HR-1 hairless mice. Cilostazol decreased wrinkle formation and skin thickness in UVB-irradiated mice, as well as increased staining of collagen fibers and inhibition of reactive oxygen species (ROS) formation in the skin. Moreover, the proteolytic activities of gelatinase matrix metalloproteinase (MMP)-9 and collagenase MMP-3 were significantly decreased in UVB-irradiated mice treated with cilostazol. Western blotting showed that UVB-induced activation of p38 mitogen-activated protein kinases (MAPK) and nuclear factor (NF)-κB was significantly inhibited by cilostazol, whereas the activation of Akt was significantly enhanced by cilostazol. Confirmation of localized protein expression in the skin revealed marked p38 MAPK and NF-κB activation that was mainly detected in the dermis. Marked Akt activation was mainly detected in the epidermis. Our results suggest that cilostazol may have anti-photoaging effects on UVB-induced wrinkle formation by maintaining the extracellular matrix density in the dermis, which occurs via regulation of ROS and related p38 MAPK and NF-κB signaling, and subsequent down-regulation of MMPs. Therefore, cilostazol may protect against photoaging-induced wrinkle formation. PMID:27484958

  10. Orally administered betaine reduces photodamage caused by UVB irradiation through the regulation of matrix metalloproteinase-9 activity in hairless mice.

    PubMed

    Im, A-Rang; Lee, Hee Jeong; Youn, Ui Joung; Hyun, Jin Won; Chae, Sungwook

    2016-01-01

    Betaine is widely distributed in plants, microorganisms, in several types of food and in medical herbs, including Lycium chinense. The administration of 100 mg betaine/kg body weight/day is an effective strategy for preventing ultraviolet irradiation‑induced skin damage. The present study aimed to determine the preventive effects of betaine on ultraviolet B (UVB) irradiation‑induced skin damage in hairless mice. The mice were divided into three groups: Control (n=5), UVB‑treated vehicle (n=5) and UVB‑treated betaine (n=5) groups. The level of irradiation was progressively increased between 60 mJ/cm2 per exposure at week 1 (one minimal erythematous dose = 60 mJ/cm2) and 90 mJ/cm2 per exposure at week 7. The formation of wrinkles significantly increased following UVB exposure in the UVB‑treated vehicle group. However, treatment with betaine suppressed UVB‑induced wrinkle formation, as determined by the mean length, mean depth, number, epidermal thickness and collagen damage. Furthermore, oral administration of betaine also inhibited the UVB‑induced expression of mitogen‑activated protein kinase kinase (MEK), extracellular signal‑regulated kinase (ERK), and matrix metalloproteinase‑9 (MMP‑9). These findings suggested that betaine inhibits UVB‑induced skin damage by suppressing increased expression of MMP‑9 through the inhibition of MEK and ERK.

  11. Polypodium leucotomos decreases UV-induced epidermal cell proliferation and enhances p53 expression and plasma antioxidant capacity in hairless mice.

    PubMed

    Rodríguez-Yanes, Esperanza; Juarranz, Ángeles; Cuevas, Jesús; Gonzalez, Salvador; Mallol, Jordi

    2012-08-01

    A single dose of ultraviolet radiation (UVR) induces significant changes in blood and skin of hairless mice. Oral administration of a hydrophilic extract of the fern Polypodium leucotomos (PL, 300 mg/kg during 5 days before UVR and for two additional days after irradiation) modulates some of the effects of UVR. Most significantly, PL administration reduced the number of proliferating cells by 13%, increased the number of p53(+) cells by 63%, enhanced the antioxidant plasma capacity (ORAC) by 30% and reinforced the network of dermal elastic fibres. Western blot analysis of skin antioxidant-related enzymes failed to demonstrate significant changes caused by PL. Thus, the beneficial effect of PL likely owes to its antioxidant and anti-ROS properties rather than its modulation of the expression of endogenous antioxidant systems. These data provide mechanistic clues for its efficacy as a systemic photoprotective agent with antioxidant and anti-photo-ageing properties.

  12. The bald and the beautiful: hairlessness in domestic dog breeds

    PubMed Central

    Harris, Alexander; Dreger, Dayna L.; Davis, Brian W.; Ostrander, Elaine A.

    2017-01-01

    An extraordinary amount of genomic variation is contained within the chromosomes of domestic dogs, manifesting as dramatic differences in morphology, behaviour and disease susceptibility. Morphology, in particular, has been a topic of enormous interest as biologists struggle to understand the small window of dog domestication from wolves, and the division of dogs into pure breeding, closed populations termed breeds. Many traits related to morphology, including body size, leg length and skull shape, have been under selection as part of the standard descriptions for the nearly 400 breeds recognized worldwide. Just as important, however, are the minor traits that have undergone selection by fanciers and breeders to define dogs of a particular appearance, such as tail length, ear position, back arch and variation in fur (pelage) growth patterns. In this paper, we both review and present new data for traits associated with pelage including fur length, curl, growth, shedding and even the presence or absence of fur. Finally, we report the discovery of a new gene associated with the absence of coat in the American Hairless Terrier breed. This article is part of the themed issue ‘Evo-devo in the genomics era, and the origins of morphological diversity’. PMID:27994129

  13. Efficacy of topical formulations containing Pimenta pseudocaryophyllus extract against UVB-induced oxidative stress and inflammation in hairless mice.

    PubMed

    Campanini, Marcela Z; Pinho-Ribeiro, Felipe A; Ivan, Ana L M; Ferreira, Vitor S; Vilela, Fernanda M P; Vicentini, Fabiana T M C; Martinez, Renata M; Zarpelon, Ana C; Fonseca, Maria J V; Faria, Terezinha J; Baracat, Marcela M; Verri, Waldiceu A; Georgetti, Sandra R; Casagrande, Rúbia

    2013-10-05

    Plants rich in antioxidant substances may be a promising strategy for preventing UV-induced oxidative and inflammatory damage of the skin. Pimenta pseudocaryophyllus is native to Brazil and presents flavonoids and other polyphenolic compounds in high concentration. Thus, the present study evaluated the possible effects of topical formulations containing P. pseudocaryophyllus ethanolic extract (PPE) at inhibiting UV-B irradiation-induced oxidative stress and inflammation. PPE was administered on the dorsal skin of hairless mice using two formulations: F1 (non-ionic emulsion with high lipid content) and F2 (anionic emulsion with low lipid content) before and after UV-B irradiation. The following parameters were evaluated in skin samples: edema, myeloperoxidase activity, cytokines levels, matrix metalloprotease-9 (MMP-9) secretion/activity, reduced glutathione (GSH), superoxide anion and lipid peroxidation levels, and mRNA expression for glutathione reductase and gp91phox. The UV-B irradiation increased all parameters, except for IL-10 levels and glutathione reductase mRNA expression, which were not altered, and GSH levels, which were reduced by exposure to UV-B light. Treatments with F1 and F2 containing PPE inhibited UV-B-induced edema formation (89% and 86%), myeloperoxidase activity (85% and 81%), IL-1β production (62% and 82%), MMP-9 activity (71% and 74%), GSH depletion (73% and 85%), superoxide anion (83% and 66%) and TBARS (100% and 100%) levels, increased glutathione reductase (2.54 and 2.55-fold) and reduced gp91phox (67% and 100%) mRNA expression, respectively. F2 containing PPE also increased IL-10 levels. Therefore, this study demonstrates the effectiveness of topical formulations containing PPE in inhibiting UV-B irradiation-induced inflammation and oxidative stress of the skin.

  14. Phenotypic and genetic characterization of a novel phenotype in pigs characterized by juvenile hairlessness and age dependent emphysema

    PubMed Central

    Bruun, Camilla S; Jørgensen, Claus B; Bay, Lene; Cirera, Susanna; Jensen, Henrik E; Leifsson, Páll S; Nielsen, Jens; Christensen, Knud; Fredholm, Merete

    2008-01-01

    Background A pig phenotype characterized by juvenile hairlessness, thin skin and age dependent lung emphysema has been discovered in a Danish pig herd. The trait shows autosomal co-dominant inheritance with all three genotypes distinguishable. Since the phenotype shows resemblance to the integrin β6 -/- knockout phenotype seen in mice, the two genes encoding the two subunits of integrin αvβ6, i.e. ITGB6 and ITGAV, were considered candidate genes for this trait. Results The mutated pig phenotype is characterized by hairlessness until puberty, thin skin with few hair follicles and absence of musculi arrectores pili, and at puberty or later localized areas of emphysema are seen in the lungs. Comparative mapping predicted that the porcine ITGB6 andITGAV orthologs map to SSC15. In an experimental family (n = 113), showing segregation of the trait, the candidate region was confirmed by linkage analysis with four microsatellite markers. Mapping of the porcine ITGB6 and ITGAV in the IMpRH radiation hybrid panel confirmed the comparative mapping information. Sequencing of the ITGB6 and ITGAV coding sequences from affected and normal pigs revealed no evidence of a causative mutation, but alternative splicing of the ITGB6 pre-mRNA was detected. For both ITGB6 and ITGAV quantitative PCR revealed no significant difference in the expression levels in normal and affected animals. In a western blot, ITGB6 was detected in lung protein samples of all three genotypes. This result was supported by flow cytometric analyses which showed comparable reactions of kidney cells from affected and normal pigs with an integrin αvβ6 monoclonal antibody. Also, immunohistochemical staining of lung tissue with an integrin β6 antibody showed immunoreaction in both normal and affected pigs. Conclusion A phenotype resembling the integrin β6 -/- knockout phenotype seen in mice has been characterized in the pig. The candidate region on SSC15 has been confirmed by linkage analysis but molecular

  15. Effect of microplasma irradiation on skin barrier function

    NASA Astrophysics Data System (ADS)

    Shimizu, Kazuo; Tran, Nhat An; Blajan, Marius

    2015-09-01

    This study investigates the feasibility of atmospheric-pressure argon microplasma irradiation (AAMI) to promote drug delivery through skin. Yucatan micropig skin was used as a biological object for evaluation of in vitro percutaneous absorption. The changes in lipids, proteins and water content of the pig stratum corneum (SC) after AAMI were compared to those of a tape stripping test (TST) and plasma jet irradiation (PJI) using attenuated total reflection-Fourier transform infrared spectroscopy analysis. The significant reduction in the methylene stretching modes absorbance resulted in the disturbance in the SC lipids caused by AAMI was observed at 2850 and 2920 cm-1. Moreover, as the result of TST, trans-epidermal water loss (TEWL) after both AAMI and PJI were also increased, that could lead to a decrease of barrier function of SC, and could enhance the transdermal absorption of drugs. Under the conditions of this study, TEWL value of 5 minutes AAMI (35.92 +/- 3.48 g/m2h) was approximately the same as that value of 10 times TST (34.30 +/- 3.54 g/m2h), that makes the effect of these manipulations on the surfaces is considered to be at the same levels. Furthermore, unlike the obtained microscopic observation from PJI, there was no thermal damage observed on the skins after AAMI.

  16. In vivo microdialysis for the investigation of drug levels in the dermis and the effect of barrier perturbation on cutaneous drug penetration. Studies in hairless rats and human subjects.

    PubMed

    Benfeldt, E

    1999-01-01

    The thesis opens with review chapters concerning theoretical and practical aspects of the investigation of drug contents in the skin. A discussion of the advantages and limitations of the established methods as well as the relatively new sampling method of microdialysis, which is employed in the experimental section, is given. Factors influencing the barrier function of the normal human skin are described as are the alterations in skin barrier function found in diseased and experimentally barrier perturbed skin. The microdialysis technique consists of introducing an ultra thin, semipermeable tube, a so-called probe, in the dermis. The tube is connected to a precision pump, which provides a steady flow of a tissue-compatible fluid through the probe at a very low flow. Smaller molecules in the tissue, among them the non-protein bound fraction of the drug content in the extracellular fluid, will passively diffuse across the surface of the membrane and thus enter the flow of the perfusate, which is sampled at regular intervals and analysed. Microdialysis is used for the determination of drug levels in the skin after topical as well as systemic drug delivery in the experimental part of the thesis. The method is not applicable to the investigation of all drugs or compounds, as we have shown that it is not feasible to sample highly protein-bound drugs or very lipophilic drugs by microdialysis without further development of the method. The investigation of topical drug administration consists of 2 studies of cutaneous penetration of a model drug, salicylic acid, initially investigated in hairless rats and subsequently in human volunteers. In both studies, barrier perturbation of the skin was undertaken by physical (removal of the stratum corneum by repeated tape stripping) or chemical (treatment with acetone) methods or by provocation of irritative dermatitis (by application of sodium lauryl sulphate, a detergent). Prior to the penetration experiment, the barrier damage

  17. [Macromutation and evolution: the fixation of Goldschmidt's macromutations as species and genus traits. Hairlessness mutations in mammals].

    PubMed

    Vorontsov, N N

    1988-06-01

    A brief survey of the development of concepts on the role of macromutations in evolution is given. Contrary to Iu. A. Filipchenko (1926, 1927), who introduced the "micro- and macromutation" terms and believed that regularities of macroevolution could not be reduced to microevolutionary processes, the majority of "synthetists" explained any form of evolution by changes in allele frequencies. From the studies of Drosophila homoeotic mutants R. Goldschmidt (1940) developed the concept of "hopeful monsters" and their role in macroevolution. However, the homoeotic mutants are of drastically reduced viability, which allows the gradualists to reject Goldschmidt's ideas. The distribution of hairlessness mutations (hairless, nude etc.) with the monogenic pattern of inheritance in mammals was studied. Hairless mutants are known in Peromyscus, Mus musculus, Rattus rattus, R. norvegicus, Canis familiaris, Ovis aries. Hairlessness as norm is found in 53 among contemporaneous 1037 mammalian genera. Part of these cases (hairlessness in all Cetacea and Sirenia) may be explained in terms of both macromutations and obligatory gradualism. There is no doubt as to the macromutational origin of hairlessness in the bat Cheiromeles and the rodent Heterocephalus (Bathyergidae); the genera systematically and ecologically close to these have normal pelage. It is quite possible that hairlessness of walrus (Odobenus) has the same origin. The appearance and fixation of single Goldschmidt's macromutation cannot yet be considered as a macroevolutionary process, though the possibility of fixation of a macromutation in nature as a species and genus character contradicts strongly the concept of obligatory gradualism of evolution.

  18. Cutaneous Uptake of 14C-HD Vapor by the Hairless Guinea Pig.

    DTIC Science & Technology

    1996-10-01

    The hairless guinea pig ( HGP ) is used by our laboratory to model the human cutaneous response to sulfur mustard (HD) exposure. We have determined the...other aspects of the experimental model. These results contribute to a better understanding of the cutaneous response to HD in the HGP model.

  19. Brief communication: Hair density and body mass in mammals and the evolution of human hairlessness.

    PubMed

    Sandel, Aaron A

    2013-09-01

    Humans are unusual among mammals in appearing hairless. Several hypotheses propose explanations for this phenotype, but few data are available to test these hypotheses. To elucidate the evolutionary history of human "hairlessness," a comparative approach is needed. One previous study on primate hair density concluded that great apes have systematically less dense hair than smaller primates. While there is a negative correlation between body size and hair density, it remains unclear whether great apes have less dense hair than is expected for their body size. To revisit the scaling relationship between hair density and body size in mammals, I compiled data from the literature on 23 primates and 29 nonprimate mammals and conducted Phylogenetic Generalized Least Squares regressions. Among anthropoids, there is a significant negative correlation between hair density and body mass. Chimpanzees display the largest residuals, exhibiting less dense hair than is expected for their body size. There is a negative correlation between hair density and body mass among the broader mammalian sample, although the functional significance of this scaling relationship remains to be tested. Results indicate that all primates, and chimpanzees in particular, are relatively hairless compared to other mammals. This suggests that there may have been selective pressures acting on the ancestor of humans and chimpanzees that led to an initial reduction in hair density. To further understand the evolution of human hairlessness, a systematic study of hair density and physiology in a wide range of species is necessary.

  20. Fisetin inhibits UVB-induced cutaneous inflammation and activation of PI3K/AKT/NFκB signaling pathways in SKH-1 hairless mice.

    PubMed

    Pal, Harish Chandra; Athar, Mohammad; Elmets, Craig A; Afaq, Farrukh

    2015-01-01

    Solar ultraviolet B (UVB) radiation has been shown to induce inflammation, DNA damage, p53 mutations and alterations in signaling pathways eventually leading to skin cancer. In this study, we investigated whether fisetin reduces inflammatory responses and modulates PI3K/AKT/NFκB cell survival signaling pathways in UVB-exposed SKH-1 hairless mouse skin. Mice were exposed to 180 mJ cm(-2) of UVB radiation on alternate days for a total of seven exposures, and fisetin (250 and 500 nmol) was applied topically after 15 min of each UVB exposure. Fisetin treatment to UVB-exposed mice resulted in decreased hyperplasia and reduced infiltration of inflammatory cells. Fisetin treatment also reduced inflammatory mediators such as COX-2, PGE2 as well as its receptors (EP1-EP4) and MPO activity. Furthermore, fisetin reduced the level of inflammatory cytokines TNFα, IL-1β and IL-6 in UVB-exposed skin. Fisetin treatment also reduced cell proliferation markers as well as DNA damage as evidenced by increased expression of p53 and p21 proteins. Further studies revealed that fisetin inhibited UVB-induced expression of PI3K, phosphorylation of AKT and activation of the NFκB signaling pathway in mouse skin. Overall, these data suggest that fisetin may be useful against UVB-induced cutaneous inflammation and DNA damage.

  1. New Methods for Evaluating Skin Injury from Sulfur Mustard in the Hairless Guinea Pig

    DTIC Science & Technology

    1993-05-13

    response curve for HD vapor doses of 2 to 4 min. This current study confirms that observation. ERYTHEMA RE’L.EC TANCE COLOR METER 0 MMI - 3 M I 5 M 1 7...essentially the same for the 5, 7, and 9 min doses. Previous work with the HGP demonstrated that the degree of erythema increased with a linear dose

  2. Comparative Morphology of Sulfur Mustard Effects in the Hairless Guinea Pig and a Human Skin Equivalent

    DTIC Science & Technology

    1993-01-01

    intercellular spaces, disruption of desmosomal attachments, nuclear pyknosis, perinuclear blebbing and repositioning of cytoplasmic tonofilaments to a...intercellular spaces, disruption of desmosomal attachments, nuclear pyknosis, perinuclear blebbing and repositioning of I| cytoplasmic tonofilaments to a...of desmosomal mal junction have been morphologically characterized. attachment. However, primary or secondary effects on specific mor- pho-biochemical

  3. Pharmacokinetics of Niacinamide in Blood and Skin of Hairless Guinea Pigs

    DTIC Science & Technology

    1993-05-13

    350 1 (45 2) V. IL K,’) 0 868 (0 141 245 ............ Z-141, REFERENCES 1. J. L. York. Enzymes. In Textbook of Biochemistry with Clinical...Correlations. T.M. Devlin , Ed., John Wiley and Sons Publishers. N. Y., USA., 1982, p. 159. 2. Ibid. p.665-670. 3. M. Weiner. Clinical Pharmacology and...Switzerland, 1971, p.1085. 5. T.M. Devlin (refe 1) p. 1212-1216. 6. R. Gugler. Clinical Pharmacokinetics of H’ipolipidaemic Drugs. Clin. Pharmacokinetics. 3

  4. Whorled hairless nevus of the scalp, linear hyperpigmentation, and telangiectatic nevi of the lower limbs: a novel variant of the "phacomatosis complex".

    PubMed

    Castori, Marco; Scarciolla, Oronzo; Morlino, Silvia; Manente, Liborio; Biscaglia, Assunta; Fragasso, Alberto; Grammatico, Paola

    2012-02-01

    The term "phacomatosis" refers to a growing number of sporadic genetic skin disorders characterized by the combination of two or more different nevi and possibly resulting from non-allelic twin spotting. While phacomatosis pigmentovascularis (PPV) and pigmentokeratotica represent the most common patterns, some patients do not fit with either condition and are temporarily classified as unique phenotypes. We report on an 8-year-old boy with striking right hemihypoplasia, resulting in limb asymmetry and fixed dislocation of right hip. Skin on the affected side showed three distinct nevi: (i) A whorled, hairless nevus of the scalp in close proximity with (ii) epidermal hyperpigmentation following lines of Blaschko on the neck and right upper limb, and (iii) multiple telangiectatic nevi of the right lower limb and hemiscrotum. Didymosis atricho-melanotica was proposed for the combination of adjacent patchy congenital alopecia and linear hyperpigmentation, while phacomatosis atricho-pigmento-vascularis appears to define the entire cutaneous phenotype, thus implying the involvement of three neighboring loci influencing the development of distinct constituents of the skin. Given the striking asymmetry of the observed phenotype, the effect of mosaicism (either genomic or functional) for a mutation in a single gene with pleiotropic action and influenced by the lateralization pattern of early development cannot be excluded.

  5. Histopathological and immunohistochemical evaluation of nitrogen mustard-induced cutaneous effects in SKH-1 hairless and C57BL/6 mice

    PubMed Central

    Jain, Anil K.; Tewari-Singh, Neera; Inturi, Swetha; Orlicky, David J.; White, Carl W.; Agarwal, Rajesh

    2014-01-01

    Sulfur mustard (SM) is a vesicant warfare agent which causes severe skin injuries. Currently, we lack effective antidotes against SM-induced skin injuries, in part due to lack of appropriate animal model(s) that can be used for efficacy studies in laboratory settings to identify effective therapies. Therefore, to develop a relevant mouse skin injury model, we examined the effects of nitrogen mustard (NM), a primary vesicant and a bifunctional alkylating agent that induces toxic effects comparable to SM. Specifically, we conducted histopathological and immunohistochemical evaluation of several applicable cutaneous pathological lesions following skin NM (3.2 mg) exposure for 12–120 h in SKH-1 and C57BL/6 mice. NM caused a significant increase in epidermal thickness, incidence of microvesication, cell proliferation, apoptotic cell death, inflammatory cells (neutrophils, macrophages and mast cells) and myleoperoxidase activity in the skin in both mouse strains. However, there was a more prominent NM-induced increase in epidermal thickness, and macrophages and mast cell infiltration, in SKH-1 mice relative to what was seen in C57BL/6 mice. NM also caused collagen degradation and edema at early time points (12–24 h); however, at later time points (72 and 120 h), dense collagen staining was observed, indicating either water loss or start of integument repair in both mouse strains. This study provides quantitative measurement of NM-induced histopathological and immunohistochemical cutaneous lesions in both hairless and haired mouse strains that could serve as useful tools for screening and identification of effective therapies for treatment of skin injuries due to NM and SM. PMID:24373750

  6. Histopathological and immunohistochemical evaluation of nitrogen mustard-induced cutaneous effects in SKH-1 hairless and C57BL/6 mice.

    PubMed

    Jain, Anil K; Tewari-Singh, Neera; Inturi, Swetha; Orlicky, David J; White, Carl W; Agarwal, Rajesh

    2014-03-01

    Sulfur mustard (SM) is a vesicant warfare agent which causes severe skin injuries. Currently, we lack effective antidotes against SM-induced skin injuries, in part due to lack of appropriate animal model(s) that can be used for efficacy studies in laboratory settings to identify effective therapies. Therefore, to develop a relevant mouse skin injury model, we examined the effects of nitrogen mustard (NM), a primary vesicant and a bifunctional alkylating agent that induces toxic effects comparable to SM. Specifically, we conducted histopathological and immunohistochemical evaluation of several applicable cutaneous pathological lesions following skin NM (3.2mg) exposure for 12-120h in SKH-1 and C57BL/6 mice. NM caused a significant increase in epidermal thickness, incidence of microvesication, cell proliferation, apoptotic cell death, inflammatory cells (neutrophils, macrophages and mast cells) and myleoperoxidase activity in the skin of both mouse strains. However, there was a more prominent NM-induced increase in epidermal thickness, and macrophages and mast cell infiltration, in SKH-1 mice relative to what was seen in C57BL/6 mice. NM also caused collagen degradation and edema at early time points (12-24h); however, at later time points (72 and 120h), dense collagen staining was observed, indicating either water loss or start of integument repair in both the mouse strains. This study provides quantitative measurement of NM-induced histopathological and immunohistochemical cutaneous lesions in both hairless and haired mouse strains that could serve as useful tools for screening and identification of effective therapies for treatment of skin injuries due to NM and SM.

  7. Oral feeding of pomegranate fruit extract inhibits early biomarkers of UVB radiation-induced carcinogenesis in SKH-1 hairless mouse epidermis.

    PubMed

    Afaq, Farrukh; Khan, Naghma; Syed, Deeba N; Mukhtar, Hasan

    2010-01-01

    Pomegranate from the plant Punica granatum L. possesses strong antioxidant and anti-inflammatory properties. Recently, we have demonstrated that treatment of normal human epidermal keratinocytes with pomegranate fruit extract (PFE) inhibited UVB-mediated activation of nuclear factor kappa B (NF-κB) and mitogen activated protein kinases pathways. Here, we evaluated the effect of PFE on early biomarkers of photocarcinogenesis employing SKH-1 hairless mice. PFE was provided in drinking water (0.2%, wt/vol) to SKH-1 hairless mice for 14 days before a single UVB (180 mJ cm(-2)) irradiation. We found that oral feeding of PFE inhibited UVB-induced: (1) skin edema; (2) hyperplasia; (3) infiltration of leukocytes; (4) lipid peroxidation; (5) hydrogen peroxide generation; (6) ornithine decarboxylase (ODC) activity; and (7) ODC, cyclooxygenase-2 and proliferating cell nuclear antigen protein expression. Oral feeding of PFE enhanced repair of UVB-mediated formation of cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). Importantly, PFE treatment further enhanced UVB-mediated increase in tumor suppressor p53 and cyclin kinase inhibitor p21. Furthermore, oral feeding of PFE inhibited UVB-mediated: (1) nuclear translocation of NF-κB; (2) activation of IKKα; and (3) phosphorylation and degradation of IκBα. Taken together, we provide evidence that oral feeding of PFE to mice affords substantial protection from the adverse effects of UVB radiation via modulation in early biomarkers of photocarcinogenesis and provide suggestion for its photochemopreventive potential.

  8. Skin Dictionary

    MedlinePlus

    ... your skin, hair, and nails Skin dictionary Camp Discovery Good Skin Knowledge lesson plans and activities Video library Find a ... your skin, hair, and nails Skin dictionary Camp Discovery Good Skin Knowledge lesson plans and activities Video library Find a ...

  9. The Near Naked Hairless (HrN) Mutation Disrupts Hair Formation but is not Due to a Mutation in the Hairless Coding Region

    SciTech Connect

    Liu, Yutao; Das, Suchita; Olszewski, Robert Edward; Culiat, Cymbeline T; Carpenter, D A; Sundberg, John P; Soteropoulos, Patricia; Liu, Xiaochen; Doktycz, Mitchel John; Michaud III, Edward J; Voy, Brynn H

    2007-01-01

    Near naked hairless (HrN) is a semi-dominant mutation that arose spontaneously and was suggested by allelism testing to be an allele of mouse Hairless (Hr). HrN mice differ from other Hr mutants in that hair loss appears as the postnatal coat begins to emerge, as opposed to failure to initiate the first postnatal hair cycle, and that the mutation displays semi-dominant inheritance. We sequenced the Hr cDNA in HrN/HrN mice and characterized the pathological and molecular phenotypes to identify the basis for hair loss in this model. HrN/HrN mice exhibit dystrophic hairs that are unable to consistently emerge from the hair follicle, while HrN/+ mice display a sparse coat of hair and a milder degree of follicular dystrophy than their homozygous littermates. DNA microarray analysis of cutaneous gene expression demonstrates that numerous genes are downregulated in HrN/HrN mice, primarily genes important for hair structure. By contrast, Hr expression is significantly increased. Sequencing the Hr coding region, intron-exon boundaries, 5'- and 3'- UTR and immediate upstream region did not reveal the underlying mutation. Therefore HrN does not appear to be an allele of Hr but may result from a mutation in a closely linked gene or from a regulatory mutation in Hr.

  10. The near-naked hairless (Hr(N)) mutation disrupts hair formation but is not due to a mutation in the Hairless coding region.

    PubMed

    Liu, Yutao; Das, Suchita; Olszewski, Robert E; Carpenter, Donald A; Culiat, Cymbeline T; Sundberg, John P; Soteropoulos, Patricia; Liu, Xiaochen; Doktycz, Mitchel J; Michaud, Edward J; Voy, Brynn H

    2007-07-01

    Near-naked hairless (Hr(N)) is a semi-dominant, spontaneous mutation that was suggested by allelism testing to be allelic with mouse Hairless (Hr). Hr(N) mice differ from other Hr mutants in that hair loss appears as the postnatal coat begins to emerge, rather than as an inability to regrow hair after the first catagen and that the mutation displays semi-dominant inheritance. We sequenced the Hr cDNA in Hr(N)/Hr(N) mice and characterized the pathological and molecular phenotypes to identify the basis for hair loss in this model. Hr(N)/Hr(N) mice exhibit dystrophic hairs that are unable to emerge consistently from the hair follicle, whereas Hr(N)/+ mice display a sparse coat of hair and a milder degree of follicular dystrophy than their homozygous littermates. DNA microarray analysis of cutaneous gene expression demonstrates that numerous genes are downregulated in Hr(N)/Hr(N) mice, primarily genes important for hair structure. By contrast, Hr expression is significantly increased. Sequencing the Hr-coding region, intron-exon boundaries, 5'- and 3'-untranslated region, and immediate upstream region did not reveal the underlying mutation. Therefore, Hr(N) does not appear to be an allele of Hr but may result from a mutation in a closely linked gene or from a regulatory mutation in Hr.

  11. A Mixture of Extracts of Kochia scoparia and Rosa multiflora with PPAR α/γ Dual Agonistic Effects Prevents Photoaging in Hairless Mice

    PubMed Central

    Jeon, Hyerin; Kim, Dong Hye; Nho, Youn-Hwa; Park, Ji-Eun; Kim, Su-Nam; Choi, Eung Ho

    2016-01-01

    Activation of peroxisome proliferator-activated receptors (PPAR) α/γ is known to inhibit the increases in matrix metalloproteinase (MMP) and reactive oxygen species (ROS) induced by ultraviolet light (UV). Extracts of natural herbs, such as Kochia scoparia and Rosa multiflora, have a PPAR α/γ dual agonistic effect. Therefore, we investigated whether and how they have an antiaging effect on photoaging skin. Eighteen-week-old hairless mice were irradiated with UVA 14 J/cm2 and UVB 40 mJ/cm2 three times a week for 8 weeks. A mixture of extracts of Kochia scoparia and Rosa multiflora (KR) was topically applied on the dorsal skin of photoaging mice twice a day for 8 weeks. Tesaglitazar, a known PPAR α/γ agonist, and vehicle (propylene glycol:ethanol = 7:3, v/v) were applied as positive and negative controls, respectively. Dermal effects (including dermal thickness, collagen density, dermal expression of procollagen 1 and collagenase 13) and epidermal effects (including skin barrier function, epidermal proliferation, epidermal differentiation, and epidermal cytokines) were measured and compared. In photoaging murine skin, KR resulted in a significant recovery of dermal thickness as well as dermal fibroblasts, although it did not change dermal collagen density. KR increased the expression of dermal transforming growth factor (TGF)-β. The dermal effects of KR were explained by an increase in procollagen 1 expression, induced by TGF-β, and a decrease in MMP-13 expression. KR did not affect basal transepidermal water loss (TEWL) or stratum corneum (SC) integrity, but did decrease SC hydration. It also did not affect epidermal proliferation or epidermal differentiation. KR decreased the expression of epidermal interleukin (IL)-1α. Collectively, KR showed possible utility as a therapeutic agent for photoaging skin, with few epidermal side effects such as epidermal hyperplasia or poor differentiation. PMID:27854351

  12. Dermal absorption and short-term biological impact in hairless mice from sunscreens containing zinc oxide nano- or larger particles

    PubMed Central

    Oytam, Yalchin; Kirby, Jason K.; Gomez-Fernandez, Laura; Baxter, Brent; McCall, Maxine J.

    2014-01-01

    Previous studies have shown no, or very limited, skin penetration of metal oxide nanoparticles following topical application of sunscreens, yet concerns remain about their safety compared to larger particles. Here, we assessed the comparative dermal absorption of a traceable form of Zn (68Zn) from 68ZnO nano-sized and larger particles in sunscreens. Sunscreens were applied to the backs of virgin or pregnant hairless mice over four days. Control groups received topical applications of the sunscreen formulation containing no ZnO particles, or no treatment. Major organs were assessed for changes in 68Zn/64Zn ratios, 68Zn tracer and total Zn concentrations. Short-term biological impact was assessed by measuring levels of serum amyloid A in blood, and by performing whole-genome transcriptional profiling on livers from each group. Increased concentrations of 68Zn tracer were detected in internal organs of mice receiving topical applications of 68ZnO (nano-sized and larger particles), as well as in fetal livers from treated dams, compared with controls. Furthermore, concentrations of 68Zn in organs of virgin mice treated with sunscreen containing 68ZnO nanoparticles were found to be significantly higher than in mice treated with sunscreen containing larger 68ZnO particles. However, no ZnO-mediated change in total Zn concentration in any of the major organs was observed. Thus, despite 68Zn absorption, which may have been in the form of soluble 68Zn species or 68ZnO particles (not known), Zn homeostasis was largely maintained, and the presence of ZnO particles in sunscreen did not elicit an adverse biological response in the mice following short-term topical applications. PMID:24266363

  13. Topical hydrocortisone, clobetasol propionate, and calcipotriol do not increase photocarcinogenesis induced by simulated solar irradiation in hairless mice.

    PubMed

    Lerche, Catharina M; Philipsen, Peter A; Poulsen, Thomas; Wulf, Hans Christian

    2010-11-01

    Topical corticosteroids such as hydrocortisone-17-butyrate (HCB) and clobetasol-17-propionate (CP) and vitamin D(3) derivatives such as calcipotriol (CAL) are widely used to treat psoriasis. The immunosuppressive effects of corticosteroids make their topical use a concern for skin carcinogenicity. Few studies have assessed the effect of topical corticosteroids and topical vitamin D(3) derivatives on photocarcinogenesis induced by ultraviolet radiation. We investigated whether HCB, CP, or CAL can accelerate photocarcinogenesis using simulated solar radiation (SSR). HCB, CP, or CAL was applied topically to the backs of hairless, female, C3.Cg/TifBomTac-immunocompetent mice in 16 groups of 25 mice each. The drugs were applied three times weekly followed by 0, 2, 4, or 6 standard erythema doses (SED) of SSR for 365 days or until death. No change was observed in the time required for tumor development in mice treated with HCB and 2 SED (HCB-2SED) and HCB-6SED. However, the time required for tumor development increased with HCB-4SED treatment. Treatment with CP-2SED did not change the time to onset of the first and second tumor, but all other CP treatments in combination with SSR increased the time. CAL-2SED decreased the time to onset of the first tumor but not of the second and third tumor. CAL-4SED and CAL-6 SED did not change or increased the time to tumor development. Our data indicated that topical administration of HCB and CAL did not alter the photocarcinogenesis of SSR and that topical CP administration had a photoprotective effect. Thus, HCB, CP, and CAL do not increase photocarcinogenesis induced by SSR.

  14. Water content and thickness of the stratum corneum contribute to skin surface morphology.

    PubMed

    Sato, J; Yanai, M; Hirao, T; Denda, M

    2000-08-01

    Skin surface morphology has long been recognized as reflecting skin pathology. In the present study, we evaluated skin surface morphology using hairless mice under contrasting conditions of humidity. The skin surface microrelief was recorded with opaque quick-drying silicone rubber, and examined under a microscope. A binary image was produced by density slicing. Within 3 days of exposure to dry conditions, skin roughness was significantly increased. The skin roughness was partially mitigated by topical application of an aqueous solution of glycerol or hydration by immersion in water. A significant correlation between skin roughness and stratum corneum thickness was also observed. These results suggest that skin surface morphology is associated with both water content and thickness of the stratum corneum.

  15. Intravital insights in skin wound healing using the mouse dorsal skin fold chamber.

    PubMed

    Sorg, Heiko; Krueger, Christian; Vollmar, Brigitte

    2007-12-01

    The skin fold chamber is one of the most accepted animal models for studying the microcirculation both in health and disease. Here we describe for the first time the alternative use of the skin fold chamber in mice for intravital microscopic investigation of skin regeneration after creating a full dermal thickness wound. The dorsal skin fold chamber was implanted in hairless SKH1-hr mice and a full dermal thickness wound (area approximately 4 mm2) was created. By means of intravital fluorescence microscopy, the kinetics of wound healing were analyzed for 12 days post wounding with assessment of epithelialization and nutritive perfusion. The morphology of the regenerating skin was characterized by hematoxylin-eosin histology and immunohistochemistry for proliferation and microvessel density. The model allows the continuous visualization of wound closure with complete epithelialization at day 12. Furthermore, a sola cutis se reficientis could be described by an inner circular ring of vessels at the wound margin surrounded by outer radial passing vessels. Inner circular vessels presented initially with large diameters and matured towards diameters of less than 15 microm for conversion into radial spreading outer vessels. Furthermore, wound healing showed all diverse core issues of skin repair. In summary, we were able to establish a model for the analysis of microcirculation in the healing skin of the mouse. This versatile model allows distinct analysis of new vessel formation and maturation in regenerating skin as well as evaluation of skin healing under different pathologic conditions.

  16. Skin Diseases: Skin Health and Skin Diseases

    MedlinePlus

    Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Skin Health and Skin Diseases Past Issues / Fall 2008 Table of Contents ... acne to wrinkles Did you know that your skin is the largest organ of your body? It ...

  17. The effect of sunscreen on skin elastase activity induced by ultraviolet-A irradiation.

    PubMed

    Tsukahara, Kazue; Moriwaki, Shigeru; Hotta, Mitsuyuki; Fujimura, Tsutomu; Sugiyama-Nakagiri, Yoriko; Sugawara, Satoshi; Kitahara, Takashi; Takema, Yoshinori

    2005-12-01

    It has been reported that application of sunscreens prevents the photoaging of skin in animal models and in humans. We irradiated the dorsal skin of hairless mice with ultraviolet-A (UVA), and investigated the effects of sunscreens on skin elastase activity and on skin properties. Six-week-old female HR/ICR hairless mice were used in these experiments. After being treated with either a UVA sunscreen (also containing ultraviolet-B (UVB) sunscreen to eliminate any slight UVB in the UVA lamps; Protection Factor of UVA (PFA)=6, Sun Protection Factor (SPF)=20) or a vehicle, the dorsal skins of mice were irradiated with the UVA lamps at 22.3 J/cm(2)/d, 5 times a week. At the end of 15 weeks skin properties were evaluated and elastase activities were measured. In the vehicle control group, UVA irradiation increased the brightness and yellowing of the skin, decreased the water content of the stratum corneum, increased skin thickness, decreased skin elasticity, increased skin elastase activity, and decreased the ability of the skin to recover in a pinch test, as compared to an unirradiated group. All these differences were statistically significant. In the UVA sunscreen group, both the UVA induced skin damage and the increase in skin elastase activity were significantly inhibited, as compared to the vehicle group. However, as compared to the unirradiated group, skin elastase activity was significantly increased and immediate extensibility of skin (Ue) was significantly decreased, thereby indicating that the UVA sunscreen did not prevent photoaging to the same level as the unirradiated group. These results suggest the partial efficacy of the topical photoprotection from UVA by the sunscreen in inhibiting elastase activation, and also suggest the possibility of reducing photoaging.

  18. Alteration of Skin Properties with Autologous Dermal Fibroblasts

    PubMed Central

    Thangapazham, Rajesh L.; Darling, Thomas N.; Meyerle, Jon

    2014-01-01

    Dermal fibroblasts are mesenchymal cells found between the skin epidermis and subcutaneous tissue. They are primarily responsible for synthesizing collagen and glycosaminoglycans; components of extracellular matrix supporting the structural integrity of the skin. Dermal fibroblasts play a pivotal role in cutaneous wound healing and skin repair. Preclinical studies suggest wider applications of dermal fibroblasts ranging from skin based indications to non-skin tissue regeneration in tendon repair. One clinical application for autologous dermal fibroblasts has been approved by the Food and Drug Administration (FDA) while others are in preclinical development or various stages of regulatory approval. In this context, we outline the role of fibroblasts in wound healing and discuss recent advances and the current development pipeline for cellular therapies using autologous dermal fibroblasts. The microanatomic and phenotypic differences of fibroblasts occupying particular locations within the skin are reviewed, emphasizing the therapeutic relevance of attributes exhibited by subpopulations of fibroblasts. Special focus is provided to fibroblast characteristics that define regional differences in skin, including the thick and hairless skin of the palms and soles as compared to hair-bearing skin. This regional specificity and functional identity of fibroblasts provides another platform for developing regional skin applications such as the induction of hair follicles in bald scalp or alteration of the phenotype of stump skin in amputees to better support their prosthetic devices. PMID:24828202

  19. Photoaging and chronological aging profile: Understanding oxidation of the skin.

    PubMed

    Peres, P S; Terra, V A; Guarnier, F A; Cecchini, R; Cecchini, A L

    2011-05-03

    The impact of chronological aging and photoaging on the skin is particularly concerning, especially when oxidative stress is involved. This article provides evidence of quantitative and qualitative differences in the oxidative stress generated by chronological aging and photoaging of the skin in HRS/J hairless mice. Analysis of the results revealed an increase in lipid peroxides as the skin gets older and in photoaged skin (10.086 ± 0.70 η MDA/mg and 14.303 ± 1.81 η MDA/mg protein, respectively), although protein oxidation was only verified in chronological aged skin (15.449 ± 0.99 η protein/mg protein). The difference between both skin types is the decay in the capacity of lipid membrane turnover revealed by the dislocation of older skin to the left in the chemiluminescence curve. Imbalance between antioxidant and oxidation processes was verified by the decrease in total antioxidant capacity of chronological and photoaged skins. Although superoxide dismutase remained unchanged, catalase increased in the 18 and 48-week-old skin groups and decreased in irradiated mice, demonstrating that neither enzyme is a good parameter to determine oxidative stress. The differences observed between chronological and photoaging skin represent a potential new approach to understanding the phenomenon of skin aging and a new target for therapeutic intervention.

  20. Alteration of skin properties with autologous dermal fibroblasts.

    PubMed

    Thangapazham, Rajesh L; Darling, Thomas N; Meyerle, Jon

    2014-05-13

    Dermal fibroblasts are mesenchymal cells found between the skin epidermis and subcutaneous tissue. They are primarily responsible for synthesizing collagen and glycosaminoglycans; components of extracellular matrix supporting the structural integrity of the skin. Dermal fibroblasts play a pivotal role in cutaneous wound healing and skin repair. Preclinical studies suggest wider applications of dermal fibroblasts ranging from skin based indications to non-skin tissue regeneration in tendon repair. One clinical application for autologous dermal fibroblasts has been approved by the Food and Drug Administration (FDA) while others are in preclinical development or various stages of regulatory approval. In this context, we outline the role of fibroblasts in wound healing and discuss recent advances and the current development pipeline for cellular therapies using autologous dermal fibroblasts. The microanatomic and phenotypic differences of fibroblasts occupying particular locations within the skin are reviewed, emphasizing the therapeutic relevance of attributes exhibited by subpopulations of fibroblasts. Special focus is provided to fibroblast characteristics that define regional differences in skin, including the thick and hairless skin of the palms and soles as compared to hair-bearing skin. This regional specificity and functional identity of fibroblasts provides another platform for developing regional skin applications such as the induction of hair follicles in bald scalp or alteration of the phenotype of stump skin in amputees to better support their prosthetic devices.

  1. Evaluation of animal models for predicting skin penetration in man.

    PubMed

    Reifenrath, W G; Chellquist, E M; Shipwash, E A; Jederberg, W W

    1984-04-01

    The human skin grafted athymic nude mouse, pig skin grafted athymic nude mouse, hairless dog, and weanling Yorkshire pig were evaluated as models for predicting skin penetration in man. Nine radiolabeled compounds previously tested on man were applied topically (4 micrograms/cm2) to each animal. These compounds included caffeine, benzoic acid, N,N-diethyl-m-toluamide, three steroids, and three insecticides. To correct for incomplete excretion of the label following topical absorption, percentage penetration was calculated by dividing the percentage of the topically applied radioactive dose recovered in the excreta by the corresponding percentage after parenteral administration and multiplication by 100. In the case of the grafted athymic nude mouse, calculated values of percentage penetration were confirmed because significant correlations (r = 0.78 for the human skin grafted athymic nude mouse and r = 0.97 for the pig skin grafted athymic nude mouse) were found between the calculated values and percentage penetration determined by summing radioactivity recovered in the urine, feces, tissues, and carcass. The results revealed a significant correlation between human skin grafted athymic nude mouse values and human values (r = 0.74, p = 0.05), and between weanling Yorkshire pig values and human values (r = 0.83, p = 0.05). In contrast, no significant correlation existed between human values and those of the hairless dog and pig skin grafted athymic nude mouse. The disposition of radioactivity following topical application of the radiolabeled nerve agent analog ( diisopropylfluorophosphonate ) and simulant (diethyl malonate) was determined in the weanling pig and the human skin grafted athymic nude mouse.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Skin Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Skin Cancer What is Skin Cancer? Skin cancer is the most common type ... of approximately 9,480 Americans in 2013. Can Skin Cancer Be Treated? Most basal cell and squamous ...

  3. Structure and Function of the Su(H)-Hairless Repressor Complex, the Major Antagonist of Notch Signaling in Drosophila melanogaster

    PubMed Central

    Torella, Rubben; Preiss, Anette; Maier, Dieter; Kovall, Rhett A.

    2016-01-01

    Notch is a conserved signaling pathway that specifies cell fates in metazoans. Receptor-ligand interactions induce changes in gene expression, which is regulated by the transcription factor CBF1/Su(H)/Lag-1 (CSL). CSL interacts with coregulators to repress and activate transcription from Notch target genes. While the molecular details of the activator complex are relatively well understood, the structure-function of CSL-mediated repressor complexes is poorly defined. In Drosophila, the antagonist Hairless directly binds Su(H) (the fly CSL ortholog) to repress transcription from Notch targets. Here, we determine the X-ray structure of the Su(H)-Hairless complex bound to DNA. Hairless binding produces a large conformational change in Su(H) by interacting with residues in the hydrophobic core of Su(H), illustrating the structural plasticity of CSL molecules to interact with different binding partners. Based on the structure, we designed mutants in Hairless and Su(H) that affect binding, but do not affect formation of the activator complex. These mutants were validated in vitro by isothermal titration calorimetry and yeast two- and three-hybrid assays. Moreover, these mutants allowed us to solely characterize the repressor function of Su(H) in vivo. PMID:27404588

  4. Release of hairless kiwifruit ‘Eldorado’ and ‘Nugget’, and ‘Early Bird’ pollinizer for further evaluation.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    UC Davis is releasing two relatively hairless kiwifruit (Actnidia chinensis) cultivars, ‘Eldorado’ and ‘Nugget’, and an early blooming male pollinizer, ‘Early Bird’. The ‘Eldorado’ bears one to two fruits on the basal nodes similar to ‘Hayward’; ‘Nugget’ bears clusters of cordate fruits on basal nod...

  5. Ultraviolet B radiation increases hairless mouse mast cells in a dose-dependent manner and alters distribution of UV-induced mast cell growth factor.

    PubMed

    Kligman, L H; Murphy, G F

    1996-01-01

    In studies of the effects of chronic UVB irradiation on dermal connective tissue in the hairless mouse, we observed that the number and size of mast cells was increased. Because mast cells are known to be associated with connective tissue remodeling, we examined and quantified the effect of increasing UVB (290-320 nm) doses on this cell. Groups of mice were exposed to filtered FS-40 Westinghouse lamps (290-400 nm: peak irradiance 313 nm) for 1-5 minimal erythema doses (MED) thrice weekly for 10 weeks. Appropriate controls were included. Biopsies, processed for light microscopy, were stained with toluidine blue. Mast cells were counted in 15 high-magnification fields per specimen with upper and lower dermis scored separately. Significant increases in large densely granular mast cells occurred at 2 MED in the lower dermis, in association with a UVB-exacerbated granulomatous reaction. In the upper dermis, mast cells were significantly increased with 3 MED. These findings suggest that mast cells may play a dual role in UV-irradiated skin with those in the lower dermis related to inflammation processes and those in the upper dermis involved in connective tissue modeling. To gain understanding of the mechanism of mast cell recruitment and maturation, we examined the effect of UVB on mast cell growth factor expression. This was enhanced in the epidermis by UVB, with a shift from cytoplasmic staining to membrane-associated or intercellular staining at 2 MED and higher. Dermal dendritic and mononuclear cells also showed increased reactivity.

  6. Singlet molecular oxygen-quenching activity of carotenoids: relevance to protection of the skin from photoaging

    PubMed Central

    Terao, Junji; Minami, Yuko; Bando, Noriko

    2011-01-01

    Carotenoids are known to be potent quenchers of singlet molecular oxygen [O2 (1Δg)]. Solar light-induced photooxidative stress causes skin photoaging by accelerating the generation of reactive oxygen species via photodynamic actions in which O2 (1Δg) can be generated by energy transfer from excited sensitizers. Thus, dietary carotenoids seem to participate in the prevention of photooxidative stress by accumulating as antioxidants in the skin. An in vivo study using hairless mice clarified that a O2 (1Δg) oxygenation-specific peroxidation product of cholesterol, cholesterol 5α-hydroperoxide, accumulates in skin lipids due to ultraviolet-A exposure. Matrix metalloproteinase-9, a metalloproteinase family enzyme responsible for the formation of wrinkles and sagging, was enhanced in the skin of ultraviolet-A -irradiated hairless mice. The activation of metalloproteinase-9 and the accumulation of 5α-hydroperoxide, as well as formation of wrinkles and sagging, were lowered in mice fed a β-carotene diet. These results strongly suggest that dietary β-carotene prevents the expression of metalloproteinase-9 (at least in part), by inhibiting the photodynamic action involving the formation of 5α-hydroperoxide in the skin. Intake of β-Carotene therefore appears to be helpful in slowing down ultraviolet-A -induced photoaging in human skin by acting as a O2 (1Δg) quencher. PMID:21297913

  7. Commentary on: Hairless and the polyamine putrescine form a negative regulatory loop in the epidermis.

    PubMed

    Ramot, Yuval; Vardy, Leah A

    2013-11-01

    Polyamines are cationic amines essential for cellular proliferation. Recently, their role in hair follicle (HF) growth has started to be explored, but their exact function is still obscure. In the October issue of Experimental Dermatology, Luke et al. follow the observation that putrescine overproducing mice and hairless (HR) mutant mice show a similar clinical phenotype of hair loss and dermal cyst formation. They show that HR and putrescine form a negative regulatory feedback mechanism, which might regulate hair cycling and therefore control hair growth. This study clearly demonstrates that a strong connection exists between HR and polyamines although there are probably additional molecular pathways involved in the polyamine regulation of hair growth which remain to be discovered.

  8. Identification of mutations in the human hairless gene in two new families with congenital atrichia.

    PubMed

    Betz, Regina C; Indelman, Margarita; Pforr, Jana; Schreiner, Felix; Bauer, Ralf; Bergman, Reuven; Lentze, Michael J; Nöthen, Markus M; Cichon, Sven; Sprecher, Eli

    2007-06-01

    Congenital atrichia (AUC) is a form of isolated alopecia with an autosomal recessive mode of inheritance. Patients are born with normal hair but this is shed almost completely during the first weeks or months of life and never regrows. In many families the development of papular lesions is noted as an additional phenotypic feature, which defines a related phenotype designated as atrichia with papular lesions (APL). Using positional cloning strategies and the molecular findings in hairless recessive (hr/hr) mice, an animal model for AUC, mutations in the human hairless gene (HR) have been identified as a cause of AUC and APL. To date, more than 20 different mutations of the HR gene have been reported in AUC and APL including different mutation types scattered over the entire HR gene length. In this report, we describe two families of Saudi Arabian and Jewish Iranian origin comprising a number of individuals with clinical features suggestive of AUC. We therefore hypothesized that affected members may carry mutations in the HR gene. After sequencing the complete coding region of the HR gene in the Saudi Arabian family, we identified a homozygous insertion of a G (c.2661dupG; p.Thr888DfsX38) in exon 12, resulting in a premature stop codon. In a Jewish Iranian patient, we identified a homozygous splice site mutation c.1557-1G > T in intron 4. The latter mutation has been previously reported in a compound heterozygous state. In the present report, we describe the second exonic insertion mutation in the human HR gene and the first mutation in exon 12. Our study emphasizes the importance of sequencing the complete coding sequence and exon/intron junctions in the molecular diagnostics of AUC and APL.

  9. Skin Conditions

    MedlinePlus

    Your skin is your body's largest organ. It covers and protects your body. Your skin Holds body fluids in, preventing dehydration Keeps harmful ... it Anything that irritates, clogs, or inflames your skin can cause symptoms such as redness, swelling, burning, ...

  10. Aging Skin

    MedlinePlus

    ... email address Submit Home > Healthy Aging > Wellness Healthy Aging Aging skin More information on aging skin When it ... treated early. Return to top More information on Aging skin Read more from womenshealth.gov Varicose Veins ...

  11. Impaired skin barrier function in mice with colon carcinoma induced by azoxymethane and dextran sodium sulfate.

    PubMed

    Yokoyama, Satoshi; Hiramoto, Keiichi; Koyama, Mayu; Ooi, Kazuya

    2015-01-01

    We have previously reported that impaired skin barrier function was induced by small intestinal injury in mice. Therefore, we postulated that other intestinal diseases might also influence skin barrier function. In this study, we evaluated the skin barrier function of hairless mice with colon carcinoma that was induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). In mice treated with these drugs, we observed elevated transepidermal water loss and reduced skin hydration levels, compared to those in the control mice. In addition, plasma nitrogen di/trioxide (NO2(-)/NO3(-)) levels were significantly elevated, and expression of type I collagen was significantly reduced in the treated mice, compared to those in control. These results suggest that impaired skin barrier function occurs in mice when colon carcinoma is present.

  12. Maintenance of the normal flora of human skin grafts transplanted to mice.

    PubMed

    Kearney, J N; Gowland, G; Holland, K T; Cunliffe, W J

    1982-10-01

    Full-thickness human cadaver skin was maintained on the dorso-lateral thoracic region of hairless mice whose immune rejection mechanism was suppressed using anti-mouse-thymocyte globulin. The bacterial profile of the pregrafted skin did not differ significantly from the normal human microflora. In contrast, the murine skin exhibited quantitative and qualitative differences from the human flora, in particular by the complete absence of Propionibacterium acnes, the dominant bacterium on sebum-rich areas of human skin. The normal microbial profile of the human grafts was maintained throughout the experimental period despite the novel environmental milieu. There was little contamination of the grafts from the normal murine flora. It was concluded that the grafted human skin would provide a realistic model for studying the ecology of human cutaneous micro-organisms.

  13. Vehicle influence on permeation through intact and compromised skin.

    PubMed

    Gujjar, Meera; Banga, Ajay K

    2014-09-10

    The purpose of this study was to compare the transdermal permeation of a model compound, diclofenac diethylamine, from a hydrophilic and lipophilic vehicle across in vitro models simulating compromised skin. Mineral oil served as a lipophilic vehicle while 10mM phosphate buffered saline served as a hydrophilic vehicle. Compromised skin was simulated by tape stripping, delipidization, or microneedle application and compared with intact skin as a control. Transepidermal water loss was measured to assess barrier function. Skin compromised with tape stripping and delipidization significantly (p<0.05) increased permeation of diclofenac diethylamine compared to intact and microneedle treated skin with phosphate buffered saline vehicle. A similar trend in permeation was observed with mineral oil as the vehicle. For both vehicles, permeation across skin increased in the same order and correlated with degree of barrier impairment as indicated by transepidermal water loss values: intacthairless rats comparing both vehicles found the same trend, with hydrophilic vehicle having greater delivery. In conclusion, phosphate buffered saline vehicle resulted in higher permeation into and across skin compared to mineral oil vehicle for all simulated models of compromised skin.

  14. Skin abscess

    MedlinePlus

    Abscess - skin; Cutaneous abscess; Subcutaneous abscess; MRSA - abscess; Staph infection - abscess ... Skin abscesses are common and affect people of all ages. They occur when an infection causes pus ...

  15. Oral collagen-derived dipeptides, prolyl-hydroxyproline and hydroxyprolyl-glycine, ameliorate skin barrier dysfunction and alter gene expression profiles in the skin.

    PubMed

    Shimizu, Jun; Asami, Naoto; Kataoka, Aya; Sugihara, Fumihito; Inoue, Naoki; Kimira, Yoshifumi; Wada, Masahiro; Mano, Hiroshi

    2015-01-09

    Oral supplementation with collagen hydrolysate (CH) has been shown to improve the condition of the skin in humans and experimental animals. Several hydroxyproline-containing oligo-peptides were previously detected in human peripheral blood after the ingestion of CH, and the two dipeptides, prolyl-hydroxyproline (PO) and hydroxyprolyl-glycine (OG), have been proposed to have beneficial effects on human health. When HR-1 hairless mice were fed a HR-AD diet, which lacked magnesium and zinc, transepidermal water loss (TEWL) increased and water content of stratum corneum decreased. In the present study, we investigated the effects of dietary PO and OG on skin barrier dysfunction in HR-1 hairless mice. Mice were fed a HR-AD diet with or without PO (0.15%) and OG (0.15%) for 35 consecutive days. The administration of PO and OG significantly decreased TEWL, and significantly increased water content of stratum corneum. A DNA microarray analysis of the dorsal skin revealed differences in gene expression between the group administered PO and OG and the control group. We also identified muscle-related Gene Ontology as a result of analyzing the up-regulated genes. These results suggested that the administration of PO and OG improved skin barrier dysfunction and altered muscle-related gene expression.

  16. Ultraviolet B-induced tumors in pigmented hairless mice, with an unsuccessful attempt to induce cutaneous melanoma.

    PubMed

    van Weelden, H; van der Putte, S C; Toonstra, J; van der Leun, J C

    1990-04-01

    An animal experiment is presented in which pigmented hairless mice were exposed once per fortnight to high doses of ultraviolet B (UVB) to study tumorigenesis. The aim of the study was to confirm a causal relationship between cutaneous melanoma and UV radiation, and to find an animal model to study it. The experiment was based on the hypothesis that the risk of developing a melanoma is increased by a history of severe sunburns. Pigmented hairless mice, Skh-hr2, were exposed once every fortnight to high doses of UVB radiation from fluorescent sunlamps, Westinghouse FS40 T12. Heavy actinic damage was observed for several days after each exposure. Seventeen of the 24 animals eventually developed tumors. Histopathologically, 80% of the tumors were squamous cell carcinomas. Depositions of melanophages were observed, but no melanomas. In this mouse experiment no causal relationship between cutaneous melanomas and UV radiation could be established.

  17. Effect of skin surface lipid on the skin permeation of lidocaine from pressure sensitive adhesives.

    PubMed

    Cheng, Y H; Hosoya, O; Sugibayashi, K; Morimoto, Y

    1994-12-01

    Pressure sensitive adhesives (PSA) tapes containing different concentrations of lidocaine were prepared by a general casting method using styrene-isoprene-styrene block copolymer, and the in vitro skin permeation of lidocaine from each tape was evaluated using diffusion cell and excised hairless rat skin. The skin permeation was proportionally increased by up to 40% lidocaine in the PSA tape and did not change after this concentration. Although the bending point of the steady-state flux via skin concentration curve was found at 40%, saturated concentration or solubility of lidocaine in the tape was estimated to be about 20% by differential scanning calorimetry (DSC) measurement. In addition, the steady-state flux of lidocaine through skin from water or silicone fluid suspension (92 or 120 micrograms/cm2.h, respectively) was very similar to those of 40, 50 and 60% tapes (105, 101 and 112 micrograms/cm2.h, respectively). Decrease in the concentration in tapes during the permeation experiment explained only part of these phenomena. To analyze them further, the drug free PSA tape with or without (control) skin surface lipid was affixed to 50% lidocaine PSA tape for 48 h, and the amount of lidocaine crystal in the layered tapes was measured by DSC. The amount was found to be lower in the lipid-containing tape than in the lipid-free tape, suggesting that skin surface lipid can dissolve lidocaine crystal or solid in PSA tape to decrease its thermodynamic activity. Thus it is important to follow the concentration and thermodynamic activity of lidocaine in PSA tape, skin and the interface between the two layers to exactly assess its skin permeation flux.

  18. Skin Biomes.

    PubMed

    Fyhrquist, N; Salava, A; Auvinen, P; Lauerma, A

    2016-05-01

    The cutaneous microbiome has been investigated broadly in recent years and some traditional perspectives are beginning to change. A diverse microbiome exists on human skin and has a potential to influence pathogenic microbes and modulate the course of skin disorders, e.g. atopic dermatitis. In addition to the known dysfunctions in barrier function of the skin and immunologic disturbances, evidence is rising that frequent skin disorders, e.g. atopic dermatitis, might be connected to a dysbiosis of the microbial community and changes in the skin microbiome. As a future perspective, examining the skin microbiome could be seen as a potential new diagnostic and therapeutic target in inflammatory skin disorders.

  19. Potential for tyndalized Lactobacillus acidophilus as an effective component in moisturizing skin and anti-wrinkle products.

    PubMed

    Im, A-Rang; Kim, Hui Seong; Hyun, Jin Won; Chae, Sungwook

    2016-08-01

    It is widely accepted that ultraviolet (UV) irradiation induces skin damage. In the present study, a UVB-induced hairless mouse model of skin photoaging was developed to determine whether tyndalized Lactobacillus acidophilus was able to significantly enhance the repair of photodamaged skin. To evaluate the effects of tyndalized L. acidophilus on UVB-induced skin-wrinkle formation in vivo, HR-1 hairless male mice were exposed to UVB radiation and orally administered tyndalized L. acidophilus. Compared with the control group, the UVB irradiation mice displayed a significant increase in transepidermal water loss and a reduction in skin hydration. In mice with UVB-induced photodamage, the effacement of the fine wrinkles by tyndalized L. acidophilus was correlated with dermal collagen synthesis, accompanied by histological changes. Furthermore, western blotting was performed to investigate the protein expression levels of matrix metalloproteinases (MMPs) and mitogen-activated protein kinase. Notably, orally administered tyndalized L. acidophilus reduced the expression levels of MMP-1 and MMP-9. Based upon the aforementioned results, it was determined that tyndalized L. acidophilus effectively inhibited the wrinkle formation induced by UVB irradiation, and that this may be attributed to the downregulation of MMPs. Therefore, tyndalized L. acidophilus may be considered a potential agent for preventing skin photoaging and wrinkle formation.

  20. Injury Thresholds for Topical Cream-Coated Skin of Hairless Guinea Pigs (Cavia Procellus) in Near Infrared Region

    DTIC Science & Technology

    2006-06-01

    five to six individual exposure locations denoted by 1 cm by 1 cm boxes using black ink marker. Surgical markers were found to smear and interfere with...shows the comparison. Table 2. Comoarison of ED50 values for 0-switched 1540 nm laser at various oulse widths and soots Experimental Setup MVL-ED50 (JcmŖ

  1. Estimation of Neutrophil Infiltration into Hairless Guinea Pig Skin treated with 2,2’ -Dichlorodiethyl Sulfide

    DTIC Science & Technology

    1993-05-13

    Biopsies were obtained from the dorsal thoracic-lumbar area of HGPs at successive 3 hr time intervals for up to 24 hrs following controlled exposure...detachment characterized previously by electron microscopy in the HGP . By 24 hrs post-exposure. the MPO levels subsided markedly (2-fold compared to...controls). These results suggest that PMNs participate in the HGP cutaneous inflammatory response following exposure to HO .ind that MPO may be a useful

  2. Iontophoretic transport through porous membranes using scanning electrochemical microscopy: application to in vitro studies of ion fluxes through skin.

    PubMed

    Scott, E R; White, H S; Phipps, J B

    1993-06-01

    Scanning electrochemical microscopy (SECM) is used to map localized iontophoretic fluxes of electroactive species through porous membranes. A method is described that allows both the rate of transport of species from a microscopic pore and the pore's diameter to be measured. SECM images and analyses of synthetic porous membranes (track-etched polycarbonate and mica membranes) and hairless mouse skin are reported. Preliminary analysis of SECM images of the mouse skin indicates that a significant percentage of the iontophoretic flux occurs through pores associated with hair follicles.

  3. Nonsense mutations in the hairless gene underlie APL in five families of Pakistani origin

    PubMed Central

    Kim, Hyunmi; Wajid, Muhammad; Kraemer, Liv; Shimomura, Yutaka; Christiano, Angela M.

    2012-01-01

    (1) Background Atrichia with papular lesions (APL) is a rare autosomal recessive form of inherited alopecia. Affected individuals present with a distinct pattern of total hair loss on the scalp, axilla and body shortly after birth and are essentially devoid of eyelashes and eyebrows. This form of hair loss is irreversible and the histology is consistent with an absence of mature hair follicles. In addition to total atrichia, APL patients also present with papules and follicular cysts filled with cornified material. Mutations in the Hairless (HR) gene have been shown to underlie APL. (2) Objective Here, we studied five unrelated large Pakistani families with clinical manifestations of APL. (3) Methods Based on previous reports of HR mutations in APL, we performed direct DNA sequencing analysis. (4) Results DNA sequencing of the HR gene in APL patients revealed three novel nonsense mutations in five unrelated families. All affected individuals were homozygous for a nonsense mutation due to C-to-T transitions at different positions in the amino acid sequence. Two families carry the mutation Q323X (CAG-TAG) in exon 3, two families harbor the mutation Q502X (CAG-TAG) in exon 6, and one family had a mutation at R940X (CGA-TGA) in exon 14. Haplotype analysis revealed that all affected individuals of both APL1 and APL16 families were homozygous for the same haplotype, and likewise, the mutation in families APL2 and APL19 was on the the same haplotype. (5) Conclusions We report three novel nonsense mutations in the HR gene in APL. Two of the newly identified mutations, Q323X and Q502X, were found to be shared between unrelated families and marker analysis confirmed an identical homozygous haplotype for APL1 and APL16, and for APL2 and APL19. These findings suggest that Q323X and Q502X did not arise independently, but instead appear to have been propagated in the population. Collectively, these findings contribute further evidence for the involvement of hairless mutations in

  4. An FTIR investigation of isocyanate skin absorption using in vitro guinea pig skin.

    PubMed

    Bello, Dhimiter; Smith, Thomas J; Woskie, Susan R; Streicher, Robert P; Boeniger, Mark F; Redlich, Carrie A; Liu, Youcheng

    2006-05-01

    Isocyanates may cause contact dermatitis, sensitization and asthma. Dermal exposure to aliphatic and aromatic isocyanates can occur in various exposure settings. The fate of isocyanates on skin is an important unanswered question. Do they react and bind to the outer layer of skin or do they penetrate through the epidermis as unreacted compounds? Knowing the kinetics of these processes is important in developing dermal exposure sampling or decontamination strategies, as well as understanding potential health implications such exposure may have. In this paper the residence time of model isocyanates on hairless guinea pig skin was investigated in vitro using attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectrometry. Model isocyanates tested were octyl isocyanate, polymeric hexamethylene diisocyanate isocyanurate (pHDI), polymeric isophorone diisocyanate isocyanurate (pIPDI) and methylenediphenyl diisocyanate (MDI). Isocyanates in ethyl acetate (30 microL) were spiked directly on the skin to give 0.2-1.8 micromol NCO cm(-2) (NCO = -N=C=O), and absorbance of the isocyanate group and other chemical groups of the molecule were monitored over time. The ATR-FTIR findings showed that polymeric isocyanates pHDI and pIPDI may remain on the skin as unreacted species for many hours, with only 15-20% of the total isocyanate group disappearing in one hour, while smaller compounds octyl isocyanate and MDI rapidly disappear from the skin surface (80+% in 30 min). Isocyanates most likely leave the skin surface by diffusion predominantly, with minimal reaction with surface proteins. The significance of these findings and their implications for dermal exposure sampling and isocyanate skin decontamination are discussed.

  5. Is lack of sleep capable of inducing DNA damage in aged skin?

    PubMed

    Kahan, V; Ribeiro, D A; Egydio, F; Barros, L A; Tomimori, J; Tufik, S; Andersen, M L

    2014-01-01

    Skin naturally changes with age, becoming more fragile. Various stimuli can alter skin integrity. The aim of this study was to evaluate whether sleep deprivation affects the integrity of DNA in skin and exacerbates the effects of aging. Fifteen-month old female Hairless mice underwent 72 h of paradoxical sleep deprivation or 15 days of chronic sleep restriction. Punch biopsies of the skin were taken to evaluate DNA damage by single cell gel (comet) assay. Neither paradoxical sleep deprivation nor sleep restriction increased genetic damage, measured by tail movement and tail intensity values. Taken together, the findings are consistent with the notion that aging overrides the effect of sleep loss on the genetic damage in elderly mice.

  6. Hairless mutation: a driving force of humanization from a human–ape common ancestor by enforcing upright walking while holding a baby with both hands

    PubMed Central

    Sutou, Shizuyo

    2012-01-01

    Three major characteristics distinguish humans from other primates: bipedality, practical nakedness, and the family as a social unit. A hairless mutation introduced into the chimpanzee/human last common ancestor (CLCA) 6 million years ago (Mya) diverged hairless human and hairy chimpanzee lineages. All primates except humans can carry their babies without using their hands. A hairless mother would be forced to stand and walk upright. Her activities would be markedly limited. The male partner would have to collect food and carry it to her by hand to keep her and their baby from starving; irresponsible and selfish males could not have left their offspring. The mother would have sexually accepted her partner at any time as a reward for food. Sexual relations irrespective of estrus cycles might have strengthened the pair bond. Molecular and paleontological dating indicates that CLCA existed 6 Mya, and early hominin fossils show that they were bipeds, indicating that humanization from CLCA occurred rapidly. A single mutation in animals with scalp hair is known to induce hairless phenotype (ectodermal dysplasia). Bipedalism and hairlessness are disadvantageous traits; only those who could survive trials and tribulations in cooperation with family members must have been able to evolve as humans. PMID:22404045

  7. Assessment of the skin photoprotective capacities of an organo-mineral broad-spectrum sunblock on two ex vivo skin models.

    PubMed

    Gélis, Christelle; Girard, Stéphanie; Mavon, Alain; Delverdier, Maxence; Paillous, Nicole; Vicendo, Patricia

    2003-10-01

    UV irradiation can cause cutaneous damage that may be specific according to the wavelength of UV rays. For example, damage from UVB irradiation manifests itself in the form of sunburn cells and enhancement of the expression of p53, while damage from UVA exposure results in an increase in the expression of vimentin. These reactions to UV irradiation were used in this work to evaluate the photoprotective capacities of two sunblock preparations that were applied to the surface of the skin. One sunblock preparation is a UVB absorber containing zinc oxide (ZnO) and titanium oxide (TiO2) exclusively. The other sunblock preparation is a new organo-mineral sunblock containing Tinosorb M, OCM, ZnO and TiO2. Evaluation of the photoprotective capacities of both preparations on hairless rat skin and on in vitro reconstructed human epidermis revealed that they were effective in preventing UVB-induced damage. In contrast, only the organo-mineral sunblock was effective in the prevention of UVA-specific damage such as dermal alterations characterized by the expression of vimentin. Furthermore, our data support the fact that hairless rat skin and in vitro reconstructed human epidermis are a reliable basis for the evaluation of the photoprotective capacities of various sunscreens against UVB and UVA damage.

  8. Increased in vivo skin penetration of quantum dots with UVR and in vitro quantum dot cytotoxicity

    NASA Astrophysics Data System (ADS)

    Mortensen, Luke; Zheng, Hong; Faulknor, Renea; De Benedetto, Anna; Beck, Lisa; DeLouise, Lisa A.

    2009-02-01

    The growing presence of quantum dots (QD) in a variety of biological, medical, and electronics applications means an increased risk of human exposure in manufacturing, research, and consumer use. However, very few studies have investigated the susceptibility of skin to penetration of QD - the most common exposure route- and the results of those that exist are conflicting. This suggests that a technique allowing determination of skin barrier status and prediction of skin permeability to QD would be of crucial interest as recent findings have provided evidence of in vitro cytotoxicity and long-term in vivo retention in the body for most QD surface chemistries. Our research focuses on barrier status of the skin (intact and with ultraviolet radiation induced barrier defect) and its impact on QD skin penetration. These model studies are particularly relevant to the common application condition of NP containing sunscreen and SPF cosmetics to UV exposed skin. Herein we present our initial efforts to develop an in vivo model of nanoparticle skin penetration using the SKH-1 hairless mouse with transepidermal water loss (TEWL) to evaluate skin barrier status and determine its ability to predict QD penetration. Our results show that ultraviolet radiation increases both TEWL and skin penetration of QD. Additionally, we demonstrate cytotoxic potential of QD to skin cells using a metastatic melanoma cell line. Our research suggests future work in specific targeting of nanoparticles, to prevent or enhance penetration. This knowledge will be used to develop powerful therapeutic agents, decreased penetration cosmetic nanoparticles, and precise skin cancer imaging modalities.

  9. In vivo analysis of internal ribosome entry at the Hairless locus by genome engineering in Drosophila.

    PubMed

    Smylla, Thomas K; Preiss, Anette; Maier, Dieter

    2016-10-07

    Cell communication in metazoans requires the highly conserved Notch signaling pathway, which is subjected to strict regulation of both activation and silencing. In Drosophila melanogaster, silencing involves the assembly of a repressor complex by Hairless (H) on Notch target gene promoters. We previously found an in-frame internal ribosome entry site in the full length H transcript resulting in two H protein isoforms (H(p120) and H(p150)). Hence, H may repress Notch signalling activity in situations where cap-dependent translation is inhibited. Here we demonstrate the in vivo importance of both H isoforms for proper fly development. To this end, we replaced the endogenous H locus by constructs specifically affecting translation of either H(p150) or H(p120) isoforms using genome engineering. Our findings indicate the functional relevance of both H proteins. Based on bristle phenotypes, the predominant isoform H(p150) appears to be of particular importance. In contrast, growth regulation and venation of the wing require the concomitant activity of both isoforms. Finally, the IRES dependent production of H(p120) during mitosis was verified in vivo. Together our data confirm IRES mediated translation of H protein in vivo, supporting strict regulation of Notch in different cellular settings.

  10. Hematological profile of the euthymic hairless guinea pig following sulfur mustard vesicant exposure.

    PubMed

    Gold, M B; Scharf, B A

    1995-01-01

    Sulfur mustard (HD) is a potent vesicating agent of military importance, with known radiomimetic properties. The euthymic hairless guinea pig (EHGP) (Cavia porcellus) is emerging as the animal model of choice for cutaneous HD study. With elucidation of the systemic effects, we may better utilize this animal for all HD toxicity work. To this end, studies were conducted to determine the definitive median lethal dose (MLD) of subcutaneously applied sulfur mustard (HD) in the EHGP, and to correlate the induced hematological changes. Eight groups of two animals each were dosed at 0.3 log intervals from an extrapolated expected dose, deriving a tentative mean around which five groups of six animals each were dosed at 0.1 log intervals, resulting in a definitive MLD of 48.17 mg kg(-1). Sulfur mustard was then administered to seven groups of six animals each at a dose of 30 mg kg(-1) and hematology performed. Significant leukocyte count suppression was found to occur on days 4, 5 and 6, following a leukocyte elevation on day 1 after exposure. Serum potassium levels were found to be elevated all 7 days after HD exposure. Establishing the MLD for subcutaneously applied HD and the pattern of induced leukocyte suppression allows for more definitive evaluation of successful toxicity counter-measures.

  11. Subcellular localization of Suppressor of Hairless in Drosophila sense organ cells during Notch signalling.

    PubMed

    Gho, M; Lecourtois, M; Géraud, G; Posakony, J W; Schweisguth, F

    1996-06-01

    During imaginal development of Drosophila, Suppressor of Hairless [Su(H)], an evolutionarily conserved transcription factor that mediates intracellular signalling by the Notch (N) receptor, controls successive alternative cell fate decisions leading to the differentiation of multicellular sensory organs. We describe here the distribution of the Su(H) protein in the wing disc epithelium throughout development of adult sense organs. Su(H) was found to be evenly distributed in the nuclei of all imaginal disc cells during sensory organ precursor cells selection. Thus differential expression and/or subcellular localization of Su(H) is not essential for its function. Soon after division of the pIIa secondary precursor cell, Su(H) specifically accumulates in the nucleus of the future socket cell. At the onset of differentiation of the socket cell, Su(H) is also detected in the cytoplasm. In this differentiating cell, N and deltex participate in the cytoplasmic retention of Su(H). Still, Su(H) does not colocalize with N at the apical-lateral membranes. These observations suggest that N regulates in an indirect manner the cytoplasmic localization of Su(H) in the socket cell. Finally, the pIIb, shaft and socket cells are found to adopt invariant positions along the anteroposterior axis of the notum. This raises the possibility that tissue-polarity biases these N-mediated cell fate choices.

  12. Skin Infections

    MedlinePlus

    ... to the touch may have yellow drainage Of cellulitis: a red, inflamed area on the skin that is tender to the touch may occur in an area of a scratch or cut redness often spreads rapidly over the skin's surface ...

  13. Skin Pigment

    MedlinePlus

    ... Diseases Take Big Slice Out of America's Health, Economy (News) Health Tip: Use Caution When Applying Hair Dye Additional ... Skin Diseases Take Big Slice Out of America's Health, Economy THURSDAY, March 2, 2017 (HealthDay News) -- Skin diseases ...

  14. Sagging Skin

    MedlinePlus

    ... Stretch Marks Sun-damaged Skin Unwanted Hair Unwanted Tattoos Varicose Veins Vitiligo Wrinkles Treatments and Procedures Ambulatory ... Stretch Marks Sun-damaged Skin Unwanted Hair Unwanted Tattoos Varicose Veins Vitiligo Wrinkles Treatments and Procedures Ambulatory ...

  15. Skin Aging

    MedlinePlus

    Your skin changes as you age. You might notice wrinkles, age spots and dryness. Your skin also becomes thinner and loses fat, making it ... heal, too. Sunlight is a major cause of skin aging. You can protect yourself by staying out ...

  16. Combined effects of iontophoretic and chemical enhancement on drug delivery. II. Transport across human and murine skin.

    PubMed

    Nolan, L M A; Corish, J; Corrigan, O I; Fitzpatrick, D

    2007-08-16

    This paper reports measurements of the release characteristics of the model drug salbutamol from a liquid crystalline vehicle across both human and hairless murine skin in vitro. The use of oleic acid and iontophoresis as penetration enhancement techniques, used separately and simultaneously, was also investigated. Over a period of 12h, salbutamol base did not diffuse from the vehicle across excised human skin while, in contrast, over a period of 2h, the drug passively transported across hairless murine skin. The diffusion co-efficient for the drug in this tissue was estimated to be 4.54+/-0.60x10(-9)cm(2)s(-1) with a permeability co-efficient of 7.03+/-0.83x10(-7)cms(-1). A current of density of 0.39mAcm(-2) facilitated a significant transport of salbutamol from the liquid crystalline vehicle across excised human skin but with a small (<0.1) transport number. The quantity of salbutamol transported across excised hairless murine skin under the same conditions was significantly greater with a transport number of 0.68. The alteration of the permeability of the tissue was less than that of the human skin and a full recovery of the pre-iontophoretic permeability of murine skin was consistently observed. The incorporation of either oleic or lauric acid into the monoglyceride component of the vehicle at a concentration of 0.1M had a marked effect on the transport of salbutamol across both human and murine skin. The initial passive permeation of the drug across the skin was not affected but the rate of drug delivery during iontophoresis was typically observed to increase by a factor greater than two. The post-iontophoretic transport of salbutamol across either tissue was also substantially enhanced in the presence of the fatty acid. The analogous use of stearic acid did not significantly influence the iontophoretic or the post-iontophoretic transport of salbutamol across excised human skin. The investigation also revealed a synergistic combination of the fatty acid and

  17. Naked but Not Hairless: The Pitfalls of Analyses of Molecular Adaptation Based on Few Genome Sequence Comparisons

    PubMed Central

    Delsuc, Frédéric; Tilak, Marie-Ka

    2015-01-01

    The naked mole-rat (Heterocephalus glaber) is the only rodent species that naturally lacks fur. Genome sequencing of this atypical rodent species recently shed light on a number of its morphological and physiological adaptations. More specifically, its hairless phenotype has been traced back to a single amino acid change (C397W) in the hair growth associated (HR) protein (or Hairless). By considering the available species diversity, we show that this specific position is in fact variable across mammals, including in the horse that was misleadingly reported to have the ancestral Cysteine. Moreover, by sequencing the corresponding HR exon in additional rodent species, we demonstrate that the C397W substitution is actually not a peculiarity of the naked mole-rat. Instead, this specific amino acid substitution is present in all hystricognath rodents investigated, which are all fully furred, including the naked mole-rat closest relative, the Damaraland mole-rat (Fukomys damarensis). Overall, we found no statistical correlation between amino acid changes at position 397 of the HR protein and reduced pilosity across the mammalian phylogeny. This demonstrates that this single amino acid change does not explain the naked mole-rat hairless phenotype. Our case study calls for caution before making strong claims regarding the molecular basis of phenotypic adaptation based on the screening of specific amino acid substitutions using only few model species in genome sequence comparisons. It also exposes the more general problem of the dilution of essential information in the supplementary material of genome papers thereby increasing the probability that misleading results will escape the scrutiny of editors, reviewers, and ultimately readers. PMID:25714745

  18. Naked but not Hairless: the pitfalls of analyses of molecular adaptation based on few genome sequence comparisons.

    PubMed

    Delsuc, Frédéric; Tilak, Marie-Ka

    2015-02-20

    The naked mole-rat (Heterocephalus glaber) is the only rodent species that naturally lacks fur. Genome sequencing of this atypical rodent species recently shed light on a number of its morphological and physiological adaptations. More specifically, its hairless phenotype has been traced back to a single amino acid change (C397W) in the hair growth associated (HR) protein (or Hairless). By considering the available species diversity, we show that this specific position is in fact variable across mammals, including in the horse that was misleadingly reported to have the ancestral Cysteine. Moreover, by sequencing the corresponding HR exon in additional rodent species, we demonstrate that the C397W substitution is actually not a peculiarity of the naked mole-rat. Instead, this specific amino acid substitution is present in all hystricognath rodents investigated, which are all fully furred, including the naked mole-rat closest relative, the Damaraland mole-rat (Fukomys damarensis). Overall, we found no statistical correlation between amino acid changes at position 397 of the HR protein and reduced pilosity across the mammalian phylogeny. This demonstrates that this single amino acid change does not explain the naked mole-rat hairless phenotype. Our case study calls for caution before making strong claims regarding the molecular basis of phenotypic adaptation based on the screening of specific amino acid substitutions using only few model species in genome sequence comparisons. It also exposes the more general problem of the dilution of essential information in the supplementary material of genome papers thereby increasing the probability that misleading results will escape the scrutiny of editors, reviewers, and ultimately readers.

  19. Sensitive skin.

    PubMed

    Misery, L; Loser, K; Ständer, S

    2016-02-01

    Sensitive skin is a clinical condition defined by the self-reported facial presence of different sensory perceptions, including tightness, stinging, burning, tingling, pain and pruritus. Sensitive skin may occur in individuals with normal skin, with skin barrier disturbance, or as a part of the symptoms associated with facial dermatoses such as rosacea, atopic dermatitis and psoriasis. Although experimental studies are still pending, the symptoms of sensitive skin suggest the involvement of cutaneous nerve fibres and neuronal, as well as epidermal, thermochannels. Many individuals with sensitive skin report worsening symptoms due to environmental factors. It is thought that this might be attributed to the thermochannel TRPV1, as it typically responds to exogenous, endogenous, physical and chemical stimuli. Barrier disruptions and immune mechanisms may also be involved. This review summarizes current knowledge on the epidemiology, potential mechanisms, clinics and therapy of sensitive skin.

  20. The sunburn cell in hairless mouse epidermis: quantitative studies with UV-A radiation and mono- and bifunctional psoralens

    SciTech Connect

    Young, A.R.; Magnus, I.A.

    1982-10-01

    The production of the sunburn cell by UV-A radiation and topical psoralens in hairless mouse epidermis has been studied. It has been shown that the appearance of this cell is dependent on the dose of both UV-A radiation and of the psoralen. The time-course with 8-methoxypsoralen has peak sunburn cell numbers at 28 hr postirradiation. A comparison of 2 bifunctional (8-methoxypsoralen and 5-methoxypsoralen) and 2 monofunctional (angelicin and 3-carbethoxypsoralen) psoralens showed the former are more potent. This suggests that DNA crosslink lesions may play a rle in sunburn cell production.

  1. Toxicokinetics of the nerve agent (+/-)-VX in anesthetized and atropinized hairless guinea pigs and marmosets after intravenous and percutaneous administration.

    PubMed

    van der Schans, Marcel J; Lander, Brenda J; van der Wiel, Herma; Langenberg, Jan P; Benschop, Hendrik P

    2003-08-15

    In continuation of our investigations on the toxicokinetics of the volatile nerve agents C(+/-)P(+/-)-soman and (+/-)-sarin, we now report on the toxicokinetics of the rather nonvolatile agent (+/-)-VX. A validated method was developed to determine blood levels of (+/-)-VX by means of achiral gas chromatography at blood levels > or =10 pg/ml. The ratio of the two enantiomers of VX in blood could be measured at levels > or =1 ng/ml by using chiral HPLC in combination with off-line gas chromatographic analysis. In order to obtain basic information on the toxicokinetics of (+/-)-VX, i.e., under conditions of 100% bioavailability, the blood levels of this agent were measured in hairless guinea pigs at iv doses corresponding with 1 and 2 LD50. The derived AUCs indicate a reasonable linearity of the toxicokinetics with dose. Also, the toxicokinetics in marmoset primates was studied at an absolute iv dose corresponding with 1 LD50 in the hairless guinea pig which led to approximately the same levels of (+/-)-VX in blood as observed at 2 LD50 in the hairless guinea pig. Finally, the toxicokinetics of (+/-)-VX were measured in hairless guinea pigs via the most relevant porte d' entrée for this agent, which is the percutaneous route at a dose corresponding with 1 LD50 (pc). Large variations were observed between individual animals in the rate of penetration of (+/-)-VX and in concomitant progression of AChE inhibition in blood of these animals. Blood levels of (+/-)-VX increased gradually over a 6-h period of time. After a 7-h penetration period, the total AUC corresponded with 2.5% bioavailability relative to iv administration. In contrast with the G-agents C(+/-)P(+/-)-soman and (+/-)-sarin, stereospecificity in the sequestration of the two enantiomers of (+/-)-VX is not a prominent phenomenon. It appears that (+/-)-VX is substantially more persistent in vivo than the two G-agents. This persistence may undermine the efficacy of pretreatment with carbamates of percutaneous

  2. Characteristics of a root hair-less line of Arabidopsis thaliana under physiological stresses

    PubMed Central

    Maeshima, Masayoshi

    2014-01-01

    The plasma membrane-associated Ca2+-binding protein-2 of Arabidopsis thaliana is involved in the growth of root hair tips. Several transgenic lines that overexpress the 23 residue N-terminal domain of this protein under the control of the root hair-specific EXPANSIN A7 promoter lack root hairs completely. The role of root hairs under normal and stress conditions was examined in one of these root hair-less lines (NR23). Compared with the wild type, NR23 showed a 47% reduction in water absorption, decreased drought tolerance, and a lower ability to adapt to heat. Growth of NR23 was suppressed in media deficient in phosphorus, iron, calcium, zinc, copper, or potassium. Also, the content of an individual mineral in NR23 grown in normal medium, or in medium lacking a specific mineral, was relatively low. In wild-type plants, the primary and lateral roots produce numerous root hairs that become elongated under phosphate-deficient conditions; NR23 did not produce root hairs. Although several isoforms of the plasma membrane phosphate transporters including PHT1;1–PHT1;6 were markedly induced after growth in phosphate-deficient medium, the levels induced in NR23 were less than half those observed in the wild type. In phosphate-deficient medium, the amounts of acid phosphatase, malate, and citrate secreted from NR23 roots were 38, 9, and 16% of the levels secreted from wild-type roots. The present results suggest that root hairs play significant roles in the absorption of water and several minerals, secretion of acid phosphatase(s) and organic acids, and in penetration of the primary roots into gels. PMID:24501179

  3. Evaluation of Imiquimod for Topical Treatment of Vaccinia Virus Cutaneous Infections in Immunosuppressed Hairless Mice

    PubMed Central

    Tarbet, E. Bart; Larson, Deanna; Anderson, Bentley J.; Bailey, Kevin W.; Wong, Min-Hui; Smee, Donald F.

    2011-01-01

    Imiquimod is an immune response modifier prescribed as a topical medication for a number of viral and neoplastic conditions. We evaluated the antiviral activity of imiquimod against vaccinia virus (WR strain) cutaneous infections in immunosuppressed (with cyclophosphamide) hairless mice when administered after virus exposure. Primary lesions progressed in severity, satellite lesions developed, and infection eventually killed the mice. Once daily topical treatment with 1% imiquimod cream for three, four, or five days were compared to twice daily topical treatment with 1% cidofovir cream for seven days. Survival time of mice in all treated groups was significantly prolonged compared to placebo controls. The mean day of death for the placebo group, three-day imiquimod, four day imiquimod, five-day imiquimod, and cidofovir groups were 15.5, 20.0, 20.5, 19.5, and 20.5 days post-infection, respectively. All treatment groups showed significant reductions in primary lesion size and in the number of satellite lesions. The cidofovir and 4-day imiquimod treatments delayed the appearance of lung virus titers by 3 and 6 days, respectively, although cutaneous lesion and snout virus titers were not as affected by treatment. Benefits in survival and lesion reduction were observed when imiquimod treatment was delayed from 24, 48 and 72 hours post-infection. However, increasing the treatment dose of imiquimod from 1% to 5% led to a significant decrease in antiviral efficacy. These results demonstrate the protective effects of topically administered imiquimod against a disseminated vaccinia virus infection in this mouse model. PMID:21439326

  4. Skin aging and dry skin.

    PubMed

    Hashizume, Hideo

    2004-08-01

    Skin aging appears to be the result of both scheduled and continuous "wear and tear" processes that damage cellular DNA and proteins. Two types of aging, chronological skin aging and photoaging, have distinct clinical and histological features. Chronological skin aging is a universal and inevitable process characterized primarily by physiologic alterations in skin function. In this case, keratinocytes are unable to properly terminally differentiate to form a functional stratum corneum, and the rate of formation of neutral lipids that contribute to the barrier function slows, causing dry, pale skin with fine wrinkles. In contrast, photoaging results from the UVR of sunlight and the damage thus becomes apparent in sun-exposed skin. Characteristics of this aging type are dry and sallow skin displaying fine wrinkles as well as deep furrows, resulting from the disorganization of epidermal and dermal components associated with elastosis and heliodermatitis. Understanding of the functions of the skin and the basic principles of moisturizer use and application is important for the prevention of skin aging. Successful treatment of dry skin with appropriate skin care products gives the impression of eternal youth.

  5. Mechanisms of synergistic skin penetration by sonophoresis and iontophoresis.

    PubMed

    Hikima, Tomohiro; Ohsumi, Shinya; Shirouzu, Kenta; Tojo, Kakuji

    2009-05-01

    The mechanism of skin penetration enhancement by ultrasound under sonophoresis (US) or by an electrical field under iontophoresis (IP) was investigated using hairless mouse skin in vitro. The seven model chemicals with different molecular weights (122-1485) were dissolved in a hydrophilic gel. Donor gel with the chemicals was loaded on the skin surface and then the skin was treated with US (300 kHz, 5.2 W/cm(2), 5.4% duty-cycle) and IP (0.32+/-0.03 mA/cm(2)) individually or with US and IP in combination (US+IP). The penetration profiles of the chemicals with a molecular weight of less than 500 were influenced by the presence of an electric charge, the profiles of ionized chemicals for US+IP were the same as profiles for IP, while the penetration flux of a non-ionized chemical synergistically increased with US+IP compared with the individual flux of US and IP. The chemicals with molecular weight of more than 1000 showed synergistic effects with US+IP. The mathematical simulation assuming a bilayer skin model revealed that the synergistic effects were mainly influenced by electroosmosis in the stratum corneum (SC). Therefore the synergistic effects of US+IP was mainly caused by the SC diffusivity of chemicals increased by US and the electroosmotic water flow by IP application.

  6. Skin optics

    SciTech Connect

    van Gemert, M.J.; Jacques, S.L.; Sterenborg, H.J.; Star, W.M.

    1989-12-01

    Quantitative dosimetry in the treatment of skin disorders with (laser) light requires information on propagation of light in the skin related to the optical properties of the individual skin layers. This involves the solution of the integro-differential equation of radiative transfer in a model representing skin geometry, as well as experimental methods to determine the optical properties of each skin layer. These activities are unified under the name skin optics. This paper first reviews the current status of tissue optics, distinguishing between the cases of: dominant absorption, dominant scattering, and scattering about equal to absorption. Then, previously published data as well as some current unpublished data on (human) stratum corneum, epidermis and dermis, have been collected and/or (re)analyzed in terms of absorption coefficient, scattering coefficient, and anisotropy factor of scattering. The results are that the individual skin layers show strongly forward scattering (anisotropy factors between 0.7 and 0.9). The absorption and scattering data show that for all wavelengths considered scattering is much more important than absorption. Under such circumstances, solutions to the transport equation for a multilayer skin model and finite beam laser irradiation are currently not yet available. Hence, any quantitative dosimetry for skin treated with (laser) light is currently lacking.

  7. Dermal Stability and In Vitro Skin Permeation of Collagen Pentapeptides (KTTKS and palmitoyl-KTTKS)

    PubMed Central

    Choi, Yun Lim; Park, Eun Ji; Kim, Eunje; Na, Dong Hee; Shin, Young-Hee

    2014-01-01

    Collagen pentapeptide (Lys-Thr-Thr-Lys-Ser, KTTKS) and its palmitoylated derivative (pal-KTTKS) have received a great deal of attention as cosmeceutical ingredients for their anti-wrinkle effects. The objective of this study was to evaluate stability and permeability of KTTKS and pal-KTTKS in hairless mouse skin. In this study, a liquid chromatography-tandem mass spectrometric method was developed for the quantification of pal-KTTKS, and used for stability and permeability studies. Stability studies were performed using skin extracts and homogenates. Both KTTKS and pal-KTTKS were rapidly degraded, but pal-KTTKS was more stable than KTTKS. When protease inhibitors were added, the stability of both compounds (KTTKS and pal-KTTKS) improved significantly. In the skin permeation study, neither KTTKS nor pal-KTTKS was detected in the receptor solution, which indicates that neither compound could permeate through the full-thickness hairless mouse skin in the experimental conditions of this study. While KTTKS was not detected in any of the skin layers (the stratum corneum, epidermis, and dermis), pal-KTTKS was observed in all skin layers: 4.2 ± 0.7 μg/cm2 in the stratum corneum, 2.8 ± 0.5 μg/cm2 in the epidermis, and 0.3 ± 0.1 μg/cm2 in the dermis. In conclusion, this study indicated that pal-KTTKS had greater stability and permeability than that of un-modified KTTKS, and may be a useful anti-wrinkle and anti-aging cosmeceutical agent. PMID:25143811

  8. Skin findings in newborns

    MedlinePlus

    Newborn skin characteristics; Infant skin characteristics; Neonatal care - skin ... the first few weeks of the baby's life. Newborn skin will vary, depending on the length of the pregnancy. Premature infants have thin, transparent skin. The skin of a ...

  9. Skin Infections

    MedlinePlus

    ... it can get infected by them. Some common types of skin infections are Bacterial: Cellulitis and impetigo. Staphylococcal infections can also affect the skin. Viral: Shingles, warts, and herpes simplex Fungal: Athlete's foot and yeast infections Parasitic: Body lice, head lice, and scabies ...

  10. Topical Delivery of Hyaluronic Acid into Skin using SPACE-peptide Carriers

    PubMed Central

    Chen, Ming; Gupta, Vivek; Anselmo, Aaron C.; Muraski, John A.; Mitragotri, Samir

    2014-01-01

    Topical penetration of macromolecules into skin is limited by their low permeability. Here, we report the use of a skin penetrating peptide, SPACE peptide, to enhance topical delivery of a macromolecule, hyaluronic acid (HA, MW: 200–325 kDa). The peptide was conjugated to phospholipids and used to prepare an ethosomal carrier system (~110 nm diameter), encapsulating HA. The SPACE-ethosomal system (SES) enhanced HA penetration into porcine skin in vitro by 7.8+/−1.1-fold compared to PBS. The system also enhanced penetration of HA in human skin in vitro, penetrating deep into the epidermis and dermis in skin of both species. In vivo experiments performed using SKH1 hairless mice also confirmed increased dermal penetration of HA using the delivery system; a 5-fold enhancement in penetration was found compared to PBS control. Concentrations of HA in skin were about 1000-fold higher than those in blood; confirming the localized nature of HA delivery into skin. The SPACE-ethosomal delivery system provides a formulation for topical delivery of macromolecules that are otherwise difficult to deliver into skin. PMID:24129342

  11. Minoxidil-containing dosage forms: skin retention and after-rinsing hair-growth promotion.

    PubMed

    Kim, Jin-Chul; Lee, Min-Ho; Rang, Moon-Jeong

    2003-01-01

    Three kinds of topical dosage forms of minoxidil (MXD), namely vesicles, double emulsions, and an inclusion complex with hydoxypropyl-beta-cyclodextrin (HP-beta-CD), were prepared. The skin retention of MXD in the preparations was evaluated in vitro using hairless mouse skins. After applying the preparations onto the skin and rinsing it, the amount of the drug left on the skin was determined using HPLC. Retention was the highest when the drug was encapsulated in cationic vesicles. Nonionic vehicle, the double emulsion, and HP-beta-CD left no significant amount of the drug after rinsing the skin. Thus, an ionic interaction between the cationic vehicle and negatively charged skin is likely responsible for the relatively high skin retention. In vivo hair growth-promotion effect of each dosage form was investigated, in which the sample application onto the clipped backs of female mice (C57BL6) and the subsequent rinsing of the backs were done once a day for 30 days. Only MXD in the cationic vesicles had hair growth promotion effect, possibly due to significant skin retention.

  12. Thymoquinone inhibits phorbol ester-induced activation of NF-κB and expression of COX-2, and induces expression of cytoprotective enzymes in mouse skin in vivo.

    PubMed

    Kundu, Joydeb Kumar; Liu, Lijia; Shin, Jun-Wan; Surh, Young-Joon

    2013-09-06

    Thymoquinone (TQ), the active ingredient of Nigella sativa, has been reported to possess anti-inflammatory and chemopreventive properties. The present study was aimed at elucidating the molecular mechanisms of anti-inflammatory and antioxidative activities of thymoquinone in mouse skin. Pretreatment of female HR-1 hairless mouse skin with TQ attenuated 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of cyclooxygenase-2 (COX-2). TQ diminished nuclear translocation and the DNA binding of nuclear factor-kappaB (NF-κB) via the blockade of phosphorylation and subsequent degradation of IκBα in TPA-treated mouse skin. Pretreatment with TQ attenuated the phosphorylation of Akt, c-Jun-N-terminal kinase and p38 mitogen-activated protein kinase, but not that of extracellular signal-regulated kinase-1/2. Moreover, topical application of TQ induced the expression of heme oxygenase-1, NAD(P)H-quinoneoxidoreductase-1, glutathione-S-transferase and glutamate cysteine ligase in mouse skin. Taken together, the inhibitory effects of TQ on TPA-induced COX-2 expression and NF-κB activation, and its ability to induce the expression of cytoprotective proteins provide a mechanistic basis of anti-inflammatory and antioxidative effects of TQ in hairless mouse skin.

  13. Skin Cancer

    MedlinePlus

    ... exposure to ultraviolet light, which is found in sunlight and in lights used in tanning salons.What ... the safe-sun guidelines.1. Avoid the sun.Sunlight damages your skin. The sun is strongest during ...

  14. Skin graft

    MedlinePlus

    ... that need skin grafts to heal Venous ulcers, pressure ulcers , or diabetic ulcers that do not heal Very ... chap 17. Read More Burns Patient Instructions Preventing pressure ulcers Surgical wound care - open Review Date 3/13/ ...

  15. Your Skin

    MedlinePlus

    ... wear sunscreen and protective clothing, such as a hat, to prevent painful sunburns. Protecting your skin now ... happens in a split second, without you ever thinking about it. previous continue Dermis = Lots of Blood ...

  16. Skin Cancer

    MedlinePlus

    ... States. The two most common types are basal cell cancer and squamous cell cancer. They usually form on the head, face, ... If not treated, some types of skin cancer cells can spread to other tissues and organs. Treatments ...

  17. Lonicera caerulea fruits reduce UVA-induced damage in hairless mice.

    PubMed

    Vostálová, Jitka; Galandáková, Adéla; Palíková, Irena; Ulrichová, Jitka; Doležal, Dalibor; Lichnovská, Radka; Vrbková, Jana; Rajnochová Svobodová, Alena

    2013-11-05

    UVA photons are less energetic than UVB photons but they are more abundant in solar radiation. Modern tools have shown that UVA light has serious adverse effects on the skin. We investigated the effect of consuming Lonicera caerulea berries on UVA-induced damage in SKH-1 mice. The mice were fed a diet containing L. caerulea berries (10%, w/w) for 14 days before a single UVA (30 J/cm(2)) treatment. Effects on haematological and antioxidant parameters were evaluated 4 and 24h after irradiation. The bioavailability of L. caerulea phenolics was also assessed. Consuming the L. caerulea berry-enriched diet caused reduced malondialdehyde production and increased catalase activity and glutathione levels were found in skin and erythrocytes. UVA-induced NADPH:quinone oxidoreductase-1 and gamma-L-glutamate-L-cysteine ligase protein in skin were reduced in mice fed L. caerulea berries. Enhanced heme oxygenase-1 level in skin, interleukin-17 in plasma and reduced interleukin-12 levels in plasma were found in the mice on the experimental diet. Histological (pyknotic) changes in the nuclei of basal cells induced by UVA exposure were reduced in L. caerulea berry consuming animals. HLPC-MS analysis showed high concentrations of hippuric acid, one of the main metabolites of aromatic amino acids and phenolic compounds, in skin, liver, urine and faeces of mice consuming the berries. Taken together, consumption of L. caerulea berries affords protection from the adverse effects of a single UVA exposure mainly via modulation of antioxidant parameters.

  18. In Vitro and In Vivo Studies on Protective Action of N-Phenethyl Caffeamide against Photodamage of Skin

    PubMed Central

    Kuo, Yueh-Hsiung; Chen, Chien-Wen; Chu, Yin; Lin, Ping; Chiang, Hsiu-Mei

    2015-01-01

    In our previous study, N-phenethyl caffeamide (K36) was proved to act as an antioxidant and an antiphotoaging agent by inhibiting type I procollagen degradation and stimulating collagen synthesis in human skin fibroblasts. In the present study, in vitro and in vivo experiments were conducted to investigate the mechanism of action and the antiinflammatory and antiphotoaging activity of K36. K36 reduced UVB-induced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthases (iNOS) expression by regulating IκB and p-IκB expression. K36 also inhibited the nuclear translocation of NF-κB. Furthermore, the inhibition of mitogen-activated protein (MAP) kinases by K36 was attributed to the downregulation of COX-2. Topically applying K36 led to efficient antiwrinkle formation and reduced UVB-induced erythema and thickness of epidermis in hairless mice. In addition, K36 penetrated into the skin of hairless mice. Our findings show that K36 has significant beneficial effects on antioxidant, antiinflammatory, and antiphotoaging activity and suggest that K36 can be developed as an antiaging agent for cosmetic and skin care products. PMID:26367260

  19. Senescent Skin

    PubMed Central

    Kushniruk, William

    1974-01-01

    The cutaneous surface is continually influenced by aging and environmental factors. A longer life span is accompanied by an increase in the frequency of problems associated with aging skin. Although most of these changes and lesions are not life threatening, the premalignant lesions must be recognized and treated. The common aging and actinic skin changes are discussed and appropriate management is described. ImagesFig. 1Fig. 2Fig. 3Fig. 4 PMID:20469067

  20. Effects of TLC-Ag dressings on skin inflammation.

    PubMed

    Bisson, Jean-François; Hidalgo-Lucas, Sophie; Bouschbacher, Marielle; Thomassin, Laetitia

    2013-06-01

    The TLC-Ag dressings, a combination of technology lipido-colloid and silver salts, are used to promote healing in wounds with risks or signs of local infection, thanks to the antimicrobial properties of the silver salts. Nanocrystalline silver dressings containing nanocrystalline silver, also used to improve wound healing, present both antimicrobial and anti-inflammatory effects. The aim of this study was to investigate the anti-inflammatory effects of TLC-Ag dressings in a model of chronic skin inflammation induced by repeated application of 12-O-tetradecanoylphorbol-13-acetate to the skin of hairless mice, in comparison with TLC dressing, Silcryst nanocrystalline dressing, desonide cream 0.05%, a corticoid cream used as positive control, and gauze. Daily treatments of the mice began 7 days after the start of induction of chronic skin inflammation and lasted for 7 days. A macroscopic score was performed daily during the treatment period until the mice killing on day 15 and skin samples were taken for histopathological analysis. TLC-Ag reduced significantly the macroscopic score of chronic skin inflammation from day 10 in comparison with gauze and TLC dressing, similarly to Silcryst nanocrystalline dressing and desonide cream, which presented the best anti-inflammatory effects. No significant differences were observed between TLC dressing and gauze. TLC-Ag reduced significantly the microscopic score of chronic skin inflammation in comparison with TLC dressing and gauze, similarly to Silcryst nanocrystalline dressing but significantly less than desonide cream. These results demonstrate that TLC-Ag dressings present significant anti-inflammatory effects on chronic skin inflammation. They can improve wound healing, due to both the antimicrobial and anti-inflammatory properties.

  1. Blackberry extract inhibits UVB-induced oxidative damage and inflammation through MAP kinases and NF-κB signalling pathways in SKH-1 mice skin

    PubMed Central

    Son, Young-Ok; Roy, Ram Vinod; Kim, Donghern; Dai, Jin; Hitron, John Andrew; Wang, Lei; Asha, Padmaja; Shi, Xianglin; Zhang, Zhuo

    2015-01-01

    Extensive exposure of solar ultraviolet-B (UVB) radiation to skin induces oxidative stress and inflammation that play a crucial role in the induction of skin cancer. Photochemoprevention with natural products represents a simple but very effective strategy for the management of cutaneous neoplasia. In this study, we investigated whether blackberry extract (BBE) reduces chronic inflammatory responses induced by UVB irradiation in SKH-1 hairless mice skin. Mice were exposed to UVB radiation (100 mJ/cm2) on alternate days for 10 weeks, and BBE (10% and 20%) was applied topically a day before UVB exposure. Our results show that BBE suppressed UVB-induced hyperplasia and reduced infiltration of inflammatory cells in the SKH-1 hairless mice skin. BBE treatment reduced glutathione (GSH) depletion, lipid peroxidation (LPO), and myeloperoxidase (MPO) in mouse skin by chronic UVB exposure. BBE significantly decreased the level of pro-inflammatory cytokines IL-6 and TNF-α in UVB-exposed skin. Likewise, UVB-induced inflammatory responses were diminished by BBE as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases, Erk1/2, p38, JNK1/2 and MKK4. Furthermore, BBE also reduced inflammatory mediators such as cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and inducible nitric oxide synthase (iNOS) levels in UVB-exposed skin. Treatment with BBE inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in mouse skin. Immunohistochemistry analysis revealed that topical application of BBE inhibited the expression of 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodG), cyclobutane pyrimidine dimers (CPD), proliferating cell nuclear antigen (PCNA), and cyclin D1 in UVB-exposed skin. Collectively, these data indicates that BBE protects from UVB-induced oxidative damage and inflammation by modulating MAP kinase and NF-κB signaling pathways. PMID:25680589

  2. Blackberry extract inhibits UVB-induced oxidative damage and inflammation through MAP kinases and NF-κB signaling pathways in SKH-1 mice skin.

    PubMed

    Divya, Sasidharan Padmaja; Wang, Xin; Pratheeshkumar, Poyil; Son, Young-Ok; Roy, Ram Vinod; Kim, Donghern; Dai, Jin; Hitron, John Andrew; Wang, Lei; Asha, Padmaja; Shi, Xianglin; Zhang, Zhuo

    2015-04-01

    Extensive exposure of solar ultraviolet-B (UVB) radiation to skin induces oxidative stress and inflammation that play a crucial role in the induction of skin cancer. Photochemoprevention with natural products represents a simple but very effective strategy for the management of cutaneous neoplasia. In this study, we investigated whether blackberry extract (BBE) reduces chronic inflammatory responses induced by UVB irradiation in SKH-1 hairless mice skin. Mice were exposed to UVB radiation (100 mJ/cm(2)) on alternate days for 10 weeks, and BBE (10% and 20%) was applied topically a day before UVB exposure. Our results show that BBE suppressed UVB-induced hyperplasia and reduced infiltration of inflammatory cells in the SKH-1 hairless mice skin. BBE treatment reduced glutathione (GSH) depletion, lipid peroxidation (LPO), and myeloperoxidase (MPO) in mouse skin by chronic UVB exposure. BBE significantly decreased the level of pro-inflammatory cytokines IL-6 and TNF-α in UVB-exposed skin. Likewise, UVB-induced inflammatory responses were diminished by BBE as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases, Erk1/2, p38, JNK1/2 and MKK4. Furthermore, BBE also reduced inflammatory mediators such as cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and inducible nitric oxide synthase (iNOS) levels in UVB-exposed skin. Treatment with BBE inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in mouse skin. Immunohistochemistry analysis revealed that topical application of BBE inhibited the expression of 8-oxo-7, 8-dihydro-2'-deoxyguanosine (8-oxodG), cyclobutane pyrimidine dimers (CPD), proliferating cell nuclear antigen (PCNA), and cyclin D1 in UVB-exposed skin. Collectively, these data indicate that BBE protects from UVB-induced oxidative damage and inflammation by modulating MAP kinase and NF-κB signaling pathways.

  3. Thymoquinone inhibits phorbol ester-induced activation of NF-κB and expression of COX-2, and induces expression of cytoprotective enzymes in mouse skin in vivo

    SciTech Connect

    Kundu, Joydeb Kumar; Liu, Lijia; Shin, Jun-Wan; Surh, Young-Joon

    2013-09-06

    Highlights: •Thymoquinone inhibits phorbol ester-induced COX-2 expression in mouse skin. •Thymoquinone attenuates phosphorylation of IκBα and DNA binding of NF-κB in mouse skin. •Thymoquinone inhibits phosphorylation of p38 MAP kinase, JNK and Akt in mouse skin. •Thymoquinone induces the expression of cytoprotective proteins in mouse skin. -- Abstract: Thymoquinone (TQ), the active ingredient of Nigella sativa, has been reported to possess anti-inflammatory and chemopreventive properties. The present study was aimed at elucidating the molecular mechanisms of anti-inflammatory and antioxidative activities of thymoquinone in mouse skin. Pretreatment of female HR-1 hairless mouse skin with TQ attenuated 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of cyclooxygenase-2 (COX-2). TQ diminished nuclear translocation and the DNA binding of nuclear factor-kappaB (NF-κB) via the blockade of phosphorylation and subsequent degradation of IκBα in TPA-treated mouse skin. Pretreatment with TQ attenuated the phosphorylation of Akt, c-Jun-N-terminal kinase and p38 mitogen-activated protein kinase, but not that of extracellular signal-regulated kinase-1/2. Moreover, topical application of TQ induced the expression of heme oxygenase-1, NAD(P)H-quinoneoxidoreductase-1, glutathione-S-transferase and glutamate cysteine ligase in mouse skin. Taken together, the inhibitory effects of TQ on TPA-induced COX-2 expression and NF-κB activation, and its ability to induce the expression of cytoprotective proteins provide a mechanistic basis of anti-inflammatory and antioxidative effects of TQ in hairless mouse skin.

  4. Ultraviolet Light B-Mediated Inhibition of Skin Catalase Activity Promotes Gr-1+CD11b+ Myeloid Cell Expansion

    PubMed Central

    Sullivan, Nicholas J.; Tober, Kathleen L.; Burns, Erin M.; Schick, Jonathan S.; Riggenbach, Judith A.; Mace, Thomas A.; Bill, Matthew A.; Young, Gregory S.; Oberyszyn, Tatiana M.; Lesinski, Gregory B.

    2011-01-01

    Skin cancer incidence and mortality are higher in men compared to women, but the causes of this sex discrepancy remain largely unknown. Ultraviolet light exposure induces cutaneous inflammation and neutralizes cutaneous antioxidants. Gr-1+CD11b+ myeloid cells are heterogeneous bone marrow-derived cells that promote inflammation-associated carcinogenesis. Reduced activity of catalase, an antioxidant present within skin, has been associated with skin carcinogenesis. We utilized the outbred, immune competent Skh-1 hairless mouse model of ultraviolet light B (UVB)-induced inflammation and non-melanoma skin cancer to further define sex discrepancies in UVB-induced inflammation. Our results demonstrated that male skin had relatively lower baseline catalase activity, which was inhibited following acute UVB exposure in both sexes. Further analysis revealed that skin catalase activity inversely correlated with splenic Gr-1+CD11b+ myeloid cell percentage. Acute UVB exposure induced Gr-1+CD11b+ myeloid cell skin infiltration, which was inhibited to a greater extent in males by topical catalase treatment. In chronic UVB studies, we demonstrated that the percentage of splenic Gr-1+CD11b+ myeloid cells was 55% higher in male tumor-bearing mice compared to their female counterparts. Together, our findings indicate that lower skin catalase activity in male mice may at least in part contribute to increased UVB-induced Gr-1+CD11b+ myeloid cells and subsequent skin carcinogenesis. PMID:22030957

  5. Angiotensin-converting enzyme inhibitor (enalapril maleate) accelerates recovery of mouse skin from UVB-induced wrinkles

    SciTech Connect

    Matsuura-Hachiya, Yuko; Arai, Koji Y.; Ozeki, Rieko; Kikuta, Ayako; Nishiyama, Toshio

    2013-12-06

    Highlights: •Angiotensin converting enzyme (ACE) increases in UVB-irradiated skin. •Administration of an ACE inhibitor improved UVB-induced skin wrinkle. •ACE inhibitor improved UVB-induced epidermal hypertrophy. •ACE inhibitor improved transepidermal water loss in the UVB-irradiated skin. -- Abstract: Angiotensin-converting enzyme (ACE) activity and angiotensin II signaling regulate cell proliferation, differentiation, and tissue remodeling, as well as blood pressure, while in skin, angiotensin II signaling is involved in wound healing, inflammation, and pathological scar formation. Therefore, we hypothesized that angiotensin II is also involved in photoaging of skin. In this study, we examined the effect of enalapril maleate, an ACE inhibitor, on recovery of wrinkled skin of hairless mice exposed to long-term UVB irradiation. Immunohistochemical observation revealed that expression of ACE, angiotensin II, and angiotensin II type 1 (AT1) and type 2 (AT2) receptors in the skin was increased after UVB irradiation (3 times/week at increasing intensities for 8 weeks). Administration of enalapril maleate (5 times/week for 6 weeks, starting 1 week after 10-week irradiation) accelerated recovery from UVB-induced wrinkles, epidermal hyperplasia and epidermal barrier dysfunction, as compared with the vehicle control. Our results indicate that ACE and angiotensin II activity are involved in skin photoaging, and suggest that ACE inhibitor such as enalapril maleate may have potential for improvement of photoaged skin.

  6. The impact of skin decontamination on the time window for effective treatment of percutaneous VX exposure.

    PubMed

    Joosen, M J A; van den Berg, R M; de Jong, A L; van der Schans, M J; Noort, D; Langenberg, J P

    2017-04-01

    The main goal of the present study was to obtain insight into depot formation and penetration following percutaneous VX poisoning, in order to identify an appropriate decontamination window that can enhance or support medical countermeasures. The study was executed in two phases, using the hairless guinea pig as an animal model. In the first phase the effect of various decontamination regimens on levels of free VX in skin and plasma were studied as well as on blood cholinesterase levels. Animals were exposed to 0.5 mg/kg VX and were not decontaminated (control), decontaminated with RSDL once at 15 or 90 min after exposure or three times at 15, 25 and 35 (10-min interval) or 15, 45 and 75 min after exposure (30-min interval). There was no significant effect of any of the decontamination regimens on the 6-h survival rate of the animals. However, all animals that had been decontaminated 15 min after exposure, showed a survival rate of more than 90%, compared to 50-60% in animals that were not decontaminated or decontaminated at 90 min after exposure. In the second phase of the study, hairless guinea pigs were exposed to 1 mg/kg VX on the shoulder, followed either by decontamination with RSDL (10 min interval), conventional treatment on indication of clinical signs or a combination thereof. It appeared that a thorough, repeated decontamination alone could not save the majority of the animals. A 100% survival rate was observed in the group that received a combination of decontamination and treatment. In conclusion, the effects of VX exposure could be influenced by various RSDL decontamination regimens. The results in freely moving animals showed that skin decontamination, although not fully effective in removing all VX from the skin and skin depot is crucial to support pharmacological intervention.

  7. Vitamin D and the skin: Physiology and pathophysiology.

    PubMed

    Bikle, Daniel D

    2012-03-01

    The keratinocytes of the skin are unique in being not only the primary source of vitamin D for the body, but in possessing both the enzymatic machinery to metabolize the vitamin D produced to active metabolites (in particular 1,25(OH)(2)D) and the vitamin D receptor (VDR) that enables the keratinocytes to respond to the 1,25(OH)(2)D thus generated. Numerous functions of the skin are regulated by vitamin D and/or its receptor. These include inhibition of proliferation, stimulation of differentiation including formation of the permeability barrier, promotion of innate immunity, regulation of the hair follicle cycle, and suppression of tumor formation. Regulation of these actions is exerted by a number of different coregulator complexes including the coactivators vitamin D receptor interacting protein (DRIP) complex also known as Mediator and the steroid receptor coactivator (SRC) family (of which SRC 2 and 3 are found in keratincytes), the inhibitor hairless (Hr), and β-catenin whose impact on VDR function is complex. Different coregulators appear to be involved in different VDR regulated functions. This review will examine the various functions of vitamin D and its receptor in the skin, and explore the mechanisms by which these functions are regulated.

  8. Multimodal optical coherence/photoacoustic tomography of skin

    NASA Astrophysics Data System (ADS)

    Alex, Aneesh P.; Zhang, Edward Z.; Považay, Boris; Laufer, Jan; Hofer, Bernd; Glittenberg, Carl; Hermann, Boris; Beard, Paul C.; Drexler, Wolfgang

    2011-03-01

    A novel non-invasive in vivo multimodal optical coherence tomography (OCT)/photoacoustic tomography (PAT) imaging system capable of obtaining structural and functional information simultaneously has been demonstrated in skin. A 1060 nm OCT system acquiring 47k depth-scans/s with ~ 7 μm axial and ~ 20 μm transverse resolutions has been incorporated into a backward-mode PA system based on a planar, optically-transparent Fabry-Perot interferometer (FPI) sensor. In this study, the excitation wavelength was set to 670 nm and a focused laser beam at 1550 nm was used as the sensor interrogation beam. OCT and PAT images were obtained sequentially and the coregistered images were combined to form the final 3D image. OCT/PAT images obtained in vivo from the skin of a hairless mouse and human palmar skin demonstrated the ability of this multimodal imaging system to provide complementary structural and functional information from deeper depths with increased contrast.

  9. Vitamin D Metabolism and Function in the Skin

    PubMed Central

    Bikle, Daniel D

    2011-01-01

    The keratinocytes of the skin are unique in being not only the primary source of vitamin D for the body, but in possessing the enzymatic machinery to metabolize vitamin D to its active metabolite 1,25(OH)2D. Furthermore, these cells also express the vitamin D receptor (VDR) that enables them to respond to the 1,25(OH)2D they produce. Numerous functions of the skin are regulated by 1,25(OH)2D and/or its receptor. These include inhibition of proliferation, stimulation of differentiation including formation of the permeability barrier, promotion of innate immunity, and promotion of the hair follicle cycle. Regulation of these actions is exerted by a number of different coregulators including the coactivators DRIP and SRC, the cosuppressor hairless (Hr), and β-catenin. This review will examine the regulation of vitamin D production and metabolism in the skin, and explore the various functions regulated by 1,25(OH)2D and its receptor. PMID:21664236

  10. Sunscreens for delay of ultraviolet induction of skin tumors

    SciTech Connect

    Wulf, H.C.; Poulsen, T.; Brodthagen, H.; Hou-Jensen, K.

    1982-08-01

    Sunscreens with different sun protection factors (SPFs) have been tested for their capability of delaying or preventing actinic damage and skin cancer development in groups of hairless, pigmented mice exposed to artificial ultraviolet (UV) light of increasing intensity. The dose delivered was less than or equal to 1 minimal erythema dose (MED) in the group of untreated mice, so that the mice to which sunscreens were applied never obtained a sunburn after UV exposure. The quality of UV light was similar to bright midday sun at a latitude of 56 degrees (city of Copenhagen). Tumorigenesis was demonstrated to be delayed corresponding to the SPF claimed by the manufacturer, but almost all of the UV-irradiated mice developed skin tumors. Histologic examination revealed actinic degeneration and tumors of squamous cell type with marked variation in differentiation. Metastases to lymph nodes and lungs were found in only 10%. Toxic reactions, such as eczematous-like skin reactions, dark coloring, and amyloidosis, were observed predominantly in the group treated with the sunscreen of highest SPF value. Long-term investigations seem to be necessary to unveil these problems--in particular, the specific SPF value, in sunscreens, that should be recommended to the public for prevention or delay of actinic damage and/or cancer development.

  11. Selective uptake of dietary tocotrienols into rat skin.

    PubMed

    Ikeda, S; Niwa, T; Yamashita, K

    2000-06-01

    Using a vitamin E mixture extracted from palm oil, the tissue distribution of dietary tocotrienols and tocopherols was examined in rats and mice. Wistar rats (4-wk-old) were fed a diet containing 48.8 mg/kg alpha-tocopherol, 45.8 mg/kg alpha-tocotrienol and 71.4 mg/kg gamma-tocotrienol for 8 wk. Nude mice (BALB/c Slc-nu, 8-wk-old) and hairless mice (SKH1, 8-wk-old) were fed the same diet for 4 wk. alpha-Tocopherol was abundantly retained in the skin, liver, kidney and plasma of rats and mice. alpha-Tocotrienol and gamma-tocotrienol were detected slightly in the liver, kidney and plasma, while substantial amounts of these tocotrienols were detected in the skin of both rats and mice. The present study suggests that the skin is a unique tissue in respect to its ability to discriminate between various vitamin E analogs.

  12. Skin lumps

    MedlinePlus

    ... DM. Dermal and subcutaneous tumors. In: James WD, Berger TG, Elston DM, eds. Andrews' Diseases of the Skin: Clinical ... Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the ...

  13. Modifications of in vitro skin penetration under solar irradiation: evaluation on flow-through diffusion cells.

    PubMed

    Gélis, Christelle; Mavon, Alain; Delverdier, Maxence; Paillous, Nicole; Vicendo, Patricia

    2002-06-01

    The effect of solar irradiation on ex vivo dermatomed hairless rat skin samples maintained in culture on flow-through diffusion cells for at least 24 h was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and by histological observations. Transepidermal water loss (TEWL) measurements and kinetic analysis of the permeation of both tritiated water and 14C caffeine through the skin were performed after full-spectrum solar exposure involving the use of a xenon arc solar simulator. After a UV exposure of less than 420 mJ/cm2, skin integrity and permeation of both water and caffeine did not change significantly. In contrast, after a 420 mJ/cm2 UV exposure, the epidermis appeared more contracted, associated with an increase of 55% of TEWL and 220% of the skin permeation of tritiated water after 6 h. The data suggested a dramatic alteration of the skin barrier integrity. Moreover, the flux of 14C caffeine increased rapidly by 338% of the absorption of water 12 h after irradiation. These results reveal the presence of a threshold UV exposure that would not modify skin penetration.

  14. Novel mechanisms for the vitamin D receptor (VDR) in the skin and in skin cancer.

    PubMed

    Bikle, Daniel D; Oda, Yuko; Tu, Chia-Ling; Jiang, Yan

    2015-04-01

    The VDR acting with or without its principal ligand 1,25(OH)2D regulates two central processes in the skin, interfollicular epidermal (IFE) differentiation and hair follicle cycling (HFC). Calcium is an important co-regulator with 1,25(OH)2D at least of epidermal differentiation. Knockout of the calcium sensing receptor (CaSR) in addition to VDR accelerates the development of skin cancer in mice on a low calcium diet. Coactivators such as mediator 1 (aka DRIP205) and steroid receptor coactivator 3 (SRC3) regulate VDR function at different stages of the differentiation process, with Med 1 essential for hair follicle differentiation and early stages of epidermal differentiation and proliferation and SRC3 essential for the latter stages of differentiation including formation of the permeability barrier and innate immunity. The corepressor of VDR, hairless (HR), is essential for hair follicle cycling, although its effect on epidermal differentiation in vivo is minimal. In its regulation of HFC and IFE VDR controls two pathways-wnt/β-catenin and sonic hedgehog (SHH). In the absence of VDR these pathways are overexpressed leading to tumor formation. Whereas, VDR binding to β-catenin may block its activation of TCF/LEF1 sites, β-catenin binding to VDR may enhance its activation of VDREs. 1,25(OH)2D promotes but may not be required for these interactions. Suppression of SHH expression by VDR, on the other hand, requires 1,25(OH)2D. The major point of emphasis is that the role of VDR in the skin involves a number of novel mechanisms, both 1,25(OH)2D dependent and independent, that when disrupted interfere with IFE differentiation and HFC, predisposing to cancer formation. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

  15. Skin Cancer Foundation

    MedlinePlus

    ... Host a Fundraising Event | About Us | Store The Skin Cancer Foundation The Skin Cancer Foundation is the ... Handbook A "Sunscreen Gene"? Skin Cancer Facts & Statistics Skin Cancer Treatment Glossary Information on medications and procedures ...

  16. Skin Pigmentation Disorders

    MedlinePlus

    Pigmentation means coloring. Skin pigmentation disorders affect the color of your skin. Your skin gets its color from a pigment called melanin. Special cells in the skin make melanin. When these cells become damaged or ...

  17. Cutaneous skin tag

    MedlinePlus

    Skin tag; Acrochordon; Fibroepithelial polyp ... have diabetes. They are thought to occur from skin rubbing against skin. ... The tag sticks out of the skin and may have a short, narrow stalk connecting it to the surface of the skin. Some skin tags are as long as ...

  18. Time course of lesion development in the hairless guinea-pig model of sulfur mustard-induced dermal injury

    PubMed Central

    Benson, Janet M.; Seagrave, JeanClare; Weber, Waylon M.; Santistevan, Colleen D.; Grotendorst, Gary R.; Schultz, Gregory S.; March, Thomas H.

    2013-01-01

    The objective of these studies was to provide detailed analyses of the time course of sulfur mustard (SM) vapor-induced clinical, histological, and biochemical changes following cutaneous exposure in hairless guinea-pigs. Three 6cm2 sites on the backs of each guinea-pig were exposed to SM vapor (314 mg3) for 6 minutes (low dose) or 12 minutes (high dose). Animals were killed at 6, 24, and 48 hours, or 2 weeks postexposure. Erythema, edema, histopathology, and analysis of matrix metalloproteinase (MMP)-2 and -9 content were evaluated. Erythema was observed by 6 hours, and edema by 24 hours postexposure. Vapor exposure caused epidermal necrosis with varying degrees of dermatitis, ulceration, hemorrhage, and separation of the dermis from the epidermis. Later changes included epidermal regeneration with hyperplasia and formation of granulation tissue in the dermis with loss of hair follicles and glandular structures. Relative amounts of pro and active MMP-2 and MMP-9 were significantly increased in the high-dose SM group at 2 weeks. Erythema, edema, and histologic changes are consistent with findings among human victims of SM attack. This model, with observations to 2 weeks, will be useful in assessing the efficacy of countermeasures against SM. PMID:21410818

  19. Molecular basis for hair loss in mice carrying a novel nonsense mutation (Hrrh-R ) in the hairless gene (Hr).

    PubMed

    Liu, Y; Sundberg, J P; Das, S; Carpenter, D; Cain, K T; Michaud, E J; Voy, B H

    2010-01-01

    Animal models carrying mutations in the hairless (Hr) gene provide a rich resource for study of hair follicle biology. A spontaneous mouse mutant with a phenotype strikingly similar to rhino mutants of Hr arose spontaneously in the mouse facility at Oak Ridge National Laboratory. Sequence analysis of Hr in these mutants uncovered a nonsense mutation in exon 12, designated as Hr(rh-R) (rhino, Oak Ridge). The mutation led to significant reduction in Hr mRNA levels, predicted to be due to nonsense-mediated decay. Histological analysis indicated dilated hair follicle infundibula at 14 days of age that rapidly became filled with cornified material. Microarray analyses revealed that expression levels of many genes involved in keratinocyte differentiation, epidermal regeneration, and wound healing were significantly upregulated before morphological detection of the phenotype, suggesting their role in onset of the Hr(rh-R) phenotype. Identification of this new Hr allele and the underlying molecular alterations allows further understanding of the role of Hr in hair follicle biology.

  20. Change in epidermal transmission due to UV-induced hyperplasia in hairless mice: a first approximation of the action spectrum.

    PubMed

    Sterenborg, H J; van der Leun, J C

    1988-04-01

    UV-induced epidermal hyperplasia was investigated by measuring the optical transmission of the epidermis of hairless mice exposed daily to ultraviolet radiation. The effects of 2 different radiation sources were investigated: Philips TUV 40W, emitting mainly 254 nm radiation, and Philips TL01 40W, emitting radiation in a narrow band around 312 nm. With both lamps a number of groups of animals were used, each receiving a different daily dose. In the experiments with both types of lamps, hyperplasia appeared to be fully determined by the accumulated dose, irrespective of the daily dose administered. This implies reciprocity between the daily dose and the time elapsed since the first exposure. Moreover, the change of transmission with time and daily dose showed very characteristic behaviour. A simple mathematical model was used to describe these changes. In a previous study we used this model to describe the results of a similar experiment with Westinghouse FS40 sunlamps. The combined data from the present and the previous experiments were used to calculate a first approximation of the action spectrum for UV-induced hyperplasia. In addition, we calculated the dose-response relationship for UV-induced increase in tolerance against ultraviolet radiation for the 3 irradiation sources.

  1. Effect of Enhancers on in vitro and in vivo Skin Permeation and Deposition of S-Methyl-L-Methionine.

    PubMed

    Kim, Ki Taek; Kim, Ji Su; Kim, Min-Hwan; Park, Ju-Hwan; Lee, Jae-Young; Lee, WooIn; Min, Kyung Kuk; Song, Min Gyu; Choi, Choon-Young; Kim, Won-Serk; Oh, Hee Kyung; Kim, Dae-Duk

    2017-03-10

    S-methyl-L-methionine (SMM), also known as vitamin U, is commercially available as skin care cosmetic products for its wound healing and photoprotective effects. However, the low skin permeation expected of SMM due to its hydrophilic nature with a log P value of -3.3, has not been thoroughly addressed. The purpose of this study thus was to evaluate the effect of skin permeation enhancers on the skin permeation/deposition of SMM. Among the enhancers tested for the in vitro skin permeation and deposition of SMM, oleic acid showed the most significant enhancing effect. Moreover, the combination of oleic acid and ethanol further enhanced in vitro permeation and deposition of SMM through hairless mouse skin. Furthermore, the combination of oleic acid and ethanol significantly increased the in vivo deposition of SMM in the epidermis/dermis for 12 hr, which was high enough to exert a therapeutic effect. Therefore, based on the in vitro and in vivo studies, the combination of oleic acid and ethanol was shown to be effective in improving the topical skin delivery of SMM, which may be applied in the cosmetic production process for SMM.

  2. Double-skin paddled superficial temporofascial flap for the reconstruction of full-thickness cheek defect.

    PubMed

    Kilinc, Hidir; Geyik, Yilmaz; Aytekin, Ahmet Hamdi

    2013-01-01

    The most common causes of cheek defects include trauma, burn, and tumor resections. In the reconstruction of the defects in this region, it is essential to use similar or adjacent tissue considering the aesthetic and functional properties. For this purpose, numerous local, regional, or distant free flaps were described. The local flaps harvested from the head and neck region are the most frequent methods because of the similar skin color, texture, and compatibility with cheek.In this study, the reconstruction in a 29-year-old male patient who had a full-thickness cheek defect due to tumor resection on the left side was performed, wherein a hairless skin island was carried through the frontal branch of superficial temporal artery for oral mucosa, and a hairy skin island through the parietal branch of the same pedicle was carried for the bearded skin defect. No complication occurred postoperatively and both aesthetic and functional satisfactory results were obtained, providing the oral mucosal and natural beard integrity. Donor-site scarring and temporal alopecia were recorded as the disadvantages of this method.This technique is a useful method for the reconstruction of full-thickness cheek defects because of its advantages including compatibility of color and texture, reliable blood supply, requiring single-session procedure, and being able to carry 2 different skin islands on the same pedicle.

  3. Cyclooxygenase-2 inhibitor nimesulide blocks ultraviolet B-induced photocarcinogenesis in SKH-1 hairless mice.

    PubMed

    Tang, Xiuwei; Kim, Arianna L; Kopelovich, Levy; Bickers, David R; Athar, Mohammad

    2008-01-01

    Cyclooxygenase-2 (COX-2) inhibition can inhibit UVB-induced carcinogenesis in the skin. We have shown that COX-2 is overexpressed in UVB-induced squamous cell carcinomas (SCCs). Celecoxib, a specific inhibitor of COX-2, blocks UVB-induced papillomas and carcinomas in murine skin. However, as COX-2 inhibitors of this type are associated with an increased risk of adverse cardiovascular events, we decided to study nimesulide, a different class of COX-2 inhibitor, an N-arylmethanesulfonamide derivative not known to have these untoward effects. To assess the antitumor-promoting effects of nimesulide, 90 mice were equally divided into three groups. Group I animals received no test agent or UVB and served as age-matched controls; group II animals were irradiated with UVB (180 mJ cm(-2), twice weekly for 35 weeks) and group III animals received 300 p.p.m. nimesulide in drinking water and were irradiated with UVB as described for group-II. Nimesulide treatment reduced the growth of UVB-induced tumors both in terms of tumor number and tumor volume. By weeks 25, 30 and 35, the tumor numbers in the nimesulide-treated group were 79%, 49% and 53% less than the number occurring in UVB-treated animals whereas tumor volume was reduced 69%, 54% and 53%, respectively, compared to the UVB-irradiated control group. Nimesulide also inhibited the malignant progression of SCCs. The reduction in tumorigenesis was paralleled by a decrease in cell cycle regulatory proteins (cyclins A, B1, D1, E, CDK2/4/6) and the antiapoptotic protein (Bcl2); concomitantly there was an increase in proapoptotic markers, poly (ADP-ribose) polymerase (PARP) and caspase-3. Nimesulide also decreased ornithine decarboxylase expression and the nuclear accumulation of nuclear factor kappa B transcriptionally active protein complexes. These results show that alternative classes of COX-2 inhibitors may likely be efficacious as cancer chemopreventive agents and may have an improved therapeutic index.

  4. The effect of topically applied salicylic compounds on serotonin-induced scratching behaviour in hairless rats.

    PubMed

    Thomsen, J S; Simonsen, L; Benfeldt, E; Jensen, S B; Serup, J

    2002-08-01

    There is a strong need for antipruritic substances for treating itch in clinical dermatology. In one recent human study, topically applied acetylsalicylic acid has been described to rapidly decrease histamine-induced itch. We have established a model for periferally elicited pruritus by injecting serotonin into the rostral back area (neck) in rats. Using this model, we aimed to investigate the antipruritic potential of four different salicylic compounds, which all possess different skin penetration characteristics. Eighteen rats were studied for 6 weeks. Prior to serotonin injections (2 mg/ml, 50 micro l), 10 micro l of test substances was applied to a circular area 18 mm in diameter. The four substances were salicylic acid, butyl salicylate, diethylamine salicylate and salicylamide, all solubilized in dimethyl isosorbide to a concentration of 5% w/w. Diethylamine salicylate and salicylamide were previously shown to be slowly absorbed through rat skin in contrast to salicylic acid and butyl salicylate. After serotonin injections, scratching was monitored by video recording for 1.5 h. Compared with the vehicle, a lower number of scratch sequences were seen when diethylamine salicylate (P < 0.001) and salicylamide (P = 0.005) had been applied. The numbers of scratch sequences were lower with diethylamine salicylate and salicylamide than with the vehicle throughout the 1.5-h study period. We conclude that topical application of diethylamine salicylate and salicylamide could suppress serotonin-induced scratching in rats. The antipruritic effect seems to be related to the slow drug release of the two substances. The results may be clinically relevant as serotonin induces itch in humans.

  5. Effects of erythropoietin in skin wound healing are dose related.

    PubMed

    Sorg, Heiko; Krueger, Christian; Schulz, Torsten; Menger, Michael D; Schmitz, Frank; Vollmar, Brigitte

    2009-09-01

    The hematopoietic growth factor erythropoietin (EPO) attracts attention due to its all-tissue-protective pleiotropic properties. We studied the effect of EPO on dermal regeneration using intravital microscopy in a model of full dermal thickness wounds in the skin-fold chamber of hairless mice. Animals received repetitive low doses or high doses of EPO (RLD-EPO or RHD-EPO) or a single high dose of EPO (SHD-EPO). SHD-EPO accelerated wound epithelialization, reduced wound cellularity, and induced maturation of newly formed microvascular networks. In contrast, RHD-EPO impaired the healing process, as indicated by delayed epithelialization, high wound cellularity, and lack of maturation of microvascular networks. Also, RHD-EPO caused an excessive erythrocyte mass and rheological malfunction, further deteriorating vessel and tissue maturation. Moreover, RHD-EPO altered fibroblast and keratinocyte migration in vitro, while both cell types exposed to RLD-EPO, and, in particular, to SHD-EPO showed accelerated wound scratch closure. In summary, our data show that a single application of a high dose of EPO accelerates and improves skin wound healing.

  6. Bifidobacterium fermented milk and galacto-oligosaccharides lead to improved skin health by decreasing phenols production by gut microbiota.

    PubMed

    Miyazaki, K; Masuoka, N; Kano, M; Iizuka, R

    2014-06-01

    A questionnaire survey found that women suffering from abnormal bowel movements have many skin problems such as a high frequency of dry skin. Although there are similarities between the structure and barrier function mechanism of the gut and skin, experimental data are insufficient to show an association between the intestinal environment and skin conditions. Phenols, for example phenol and p-cresol, as metabolites of aromatic amino acids produced by gut bacteria, are regarded as bioactive toxins and serum biomarkers of a disturbed gut environment. Recent studies have demonstrated that phenols disturb the differentiation of monolayer-cultured keratinocytes in vitro, and that phenols produced by gut bacteria accumulate in the skin via the circulation and disrupt keratinocyte differentiation in hairless mice. Human studies have demonstrated that restriction of probiotics elevated serum free p-cresol levels and harmed skin conditions (reduced skin hydration, disrupted keratinisation). In contrast, daily intake of the prebiotic galacto-oligosaccharides (GOS) restored serum free p-cresol levels and skin conditions in adult women. Moreover, a double-blind placebo-controlled trial demonstrated that the daily intake of fermented milk containing the probiotic Bifidobacterium breve strain Yakult and prebiotic GOS reduced serum total phenol levels and prevented skin dryness and disruption of keratinisation in healthy adult women. It is concluded that phenols produced by gut bacteria are one of the causes of skin problems. Probiotics and/or prebiotics, such as B. breve strain Yakult and/or GOS, are expected to help maintain a healthy skin by decreasing phenols production by gut microbiota. These findings support the hypothesis that probiotics and prebiotics provide health benefits to the skin as well as the gut.

  7. High-Throughput Screening of Potential Skin Penetration-Enhancers Using Stratum Corneum Lipid Liposomes: Preliminary Evaluation for Different Concentrations of Ethanol

    PubMed Central

    Kitao, Yuki

    2017-01-01

    In this study, we developed a technique for high-throughput screening (HTS) of skin penetration-enhancers using stratum corneum lipid liposomes (SCLLs). A fluorescent marker, sodium fluorescein (FL), entrapped in SCLLs was prepared to provide a preliminary evaluation of the effect of different concentrations of ethanol on the disruption effect of SCLLs, which is an alternative for skin penetration-enhancing effects. In addition, SCLLs containing a fluorescent probe (DPH, TMA-DPH, or ANS) were also prepared and utilized to investigate SCLL fluidity. The results using SCLL-based techniques were compared with conventional skin permeation and skin impedance test using hairless rat skin. The obtained correlations were validated between FL leakage, SCLL fluidity with various probes, or skin impedance and increases in the skin permeation enhancement ratio (ER) of caffeine as a model penetrant. As a result, FL leakage and SCLL fluidity using ANS were considered to be good indices for the skin penetration-enhancing effect, suggesting that the action of ethanol on the SC lipid and penetration-enhancing is mainly on the polar head group of intercellular lipids. In addition, this screening method using SCLL could be utilized as an alternative HTS technique for conventional animal tests. Simultaneously, the method was found to be time-saving and sensitive compared with a direct assay using human and animal skins. PMID:28321359

  8. Management of skin-related adverse events during locomotor training with robotic-assisted body weight supported treadmill: A case report.

    PubMed

    Kelley, Carolyn P; Childress, Jason; Noser, Elizabeth A

    2013-05-01

    The purpose of this case report is to describe attempts to prevent skin-related adverse events from occurring and protect the skin once breakdown occurred in a person with chronic stroke during locomotor training. There is scant literature in how to address skin during locomotor training with the Lokomat(®), particularly when a patient presents with sensory deficits and frail skin. The patient was a 75-year-old male survivor of stroke who participated in the Lokomat(®) group of a randomized clinical pilot study comparing locomotor training with the Lokomat(®) and conventional means. He had diminished sensation to light touch and proprioception on his left leg with skin on both lower legs presenting as thin, flaky, and virtually hairless. Although much effort was put towards prevention of skin breakdown, he developed numerous skin-related adverse events during his training. However, his skin healed completely with reduced training intensity and initiation of "pre-wrapping" his lower legs with Akton(®) viscoelastic polymer sheets and elastic bandages. Significant improvements were noted in his Functional Improvement Measure(™) locomotion score and Stroke Impact Scale domains of strength, participation/role function, and total recovery, though not in his 10-m walk test velocity or 6-min walk test. The Akton(®) sheets and team approach between study team, patient, and his wife allowed simultaneous safe continuation of locomotor training with the Lokomat(®) and healing of his skin breakdown.

  9. Skin Keratins

    PubMed Central

    Wang, Fengrong; Zieman, Abigail; Coulombe, Pierre A.

    2016-01-01

    Keratins comprise the type I and type II intermediate filament-forming proteins and occur primarily in epithelial cells. They are encoded by 54 evolutionarily conserved genes (28 type I, 26 type II) and regulated in a pairwise and tissue type-, differentiation-, and context-dependent manner. Keratins serve multiple homeostatic and stress-enhanced mechanical and nonmechanical functions in epithelia, including the maintenance of cellular integrity, regulation of cell growth and migration, and protection from apoptosis. These functions are tightly regulated by posttranslational modifications as well as keratin-associated proteins. Genetically determined alterations in keratin-coding sequences underlie highly penetrant and rare disorders whose pathophysiology reflects cell fragility and/or altered tissue homeostasis. Moreover, keratin mutation or misregulation represents risk factors or genetic modifiers for several acute and chronic diseases. This chapter focuses on keratins that are expressed in skin epithelia, and details a number of basic protocols and assays that have proven useful for analyses being carried out in skin. PMID:26795476

  10. Skin (Pressure) Sores

    MedlinePlus

    ... Treatments and Side Effects Managing Cancer-related Side Effects Skin Problems Pressure Sores A skin or pressure sore ... Content Usage Policy . Skin Problems Dry Skin Itching Skin Color Changes Pressure Sores Scars ... and Paying for Treatment Treatments and Side Effects Survivorship: During and After Treatment Caregivers and Family ...

  11. Topical AC-11 abates actinic keratoses and early squamous cell cancers in hairless mice exposed to Ultraviolet A (UVA) radiation.

    PubMed

    Mentor, Julian M; Etemadi, Amir; Patta, Abrienne M; Scheinfeld, Noah

    2015-04-16

    AC-11 is an aqueous extract of the botanical, Uncaria tomentosa, which has a variety of effects that enhance DNA repair and down regulate inflammation. AC-11 is essentially free of oxindole alkaloids (< 0.05%, w/w) but contains more than 8% carboxy alkyl esters (CAEs) as their active ingredients. Three groups of 10 outbred SK-1 hairless or SK-II hairless strains of mice each were treated with AC-11 at 0.5%, 1.5%, and 3.0% in a non-irritating, dye-free, perfume-free, and fragrance-free vanishing cream vehicle. Ten mice used vehicle only and 10 were untreated. Each concentration of AC-11 and was applied daily to the backs of the mice prior to exposure to a 1,600-watt solar simulator used in this work (Solar Light Co. Philadelphia, PA) emitting (mainly Ultraviolet A (UVA) and B (UVB) radiation) duration of the experimental period with UVB wavelengths was filtered out with a 1.0 cm Schott WG 345 filter. AC-11 with a peak absorption at 200nm does act as a sun block. We tested for and focused on clinical appearance of mice and histological appearance of tumors in mice rather than metrics of radiation generated inflammation. Tumor progression scores were assigned as follows: 4+ = extensive tumor development; 3+ = early malignancies (raised palpable plaques)(early squamous cell cancers) 2+ = firm scaling, palpable keratosis (actinic keratoses); 1+ = light scaling with erythema. Following a total cumulative dose of 738 J/cm2, 85.7% all of the irradiated control animals, which did not receive AC-11 had precancerous actinic keratosis (AK)-type lesions (2+) (64.3% versus 42.9%) or early squamous cell carcinoma (SCC) (3+) (21.4% vs. 4.8%), in comparison with 47.7 % of AC-11-treated animals. There were no significant differences between the AC-11 groups. Three months after cessation of exposure to UVA radiation, the lesions in all but three of the 14 animals which were treated with AC-11 that were still evaluable irradiated with UVA radiation progressed to papillomas and frank

  12. Evaluation of skin damage caused by percutaneous absorption enhancers using fractal analysis.

    PubMed

    Obata, Y; Sesumi, T; Takayama, K; Isowa, K; Grosh, S; Wick, S; Sitz, R; Nagai, T

    2000-04-01

    Fractal analysis of the cross-sectional morphology of rat skin was conducted to evaluate pathologic changes evoked by percutaneous absorption enhancers. Male hairless rats (WBN/Ht-ILA), 8 weeks old, weighing 160 to 180 g were used. Under anesthetization, glass cells (10-mm inner diameter) were attached to the rats' abdomens, and test solutions containing various mixtures of the percutaneous absorption enhancers, sodium lauryl sulfate, isopropanol, 2-methyl-1-butanol, and sodium myristate were applied. Six hours after application, the solutions were removed and the abdominal skin was excised. Skin cross sections were analyzed with a charge-coupled device (CCD) camera. Image data taken by the CCD camera were fed into a desktop digital computer; then the fractal dimension of each skin cross section was determined on the basis of the box-counting algorithm. A pathologic study was also performed on the skin treated with the test solution. All sections of skin were examined with an optical photo microscope. Pathologic findings were classified into five levels. The total irritation score (TIS) was defined as the summation of damage levels in all regions. Only with the administration of hydrogel containing 2-methyl-1-butanol or sodium lauryl sulfate were positive values of TIS observed. However, the TIS values were independent of the concentration of these components. The most severe skin damage was evoked by application of sodium lauryl sulfate. Noticeable skin damage was also seen with 2-methyl-1-butanol. No irritation to the skin resulted from treatment with isopropanol or sodium myristate. When test solution containing sodium lauryl sulfate was applied to the skin, a remarkable increment in fractal dimensions was noted. This may suggest that the structure of the skin was greatly compromised as a result of sodium lauryl sulfate application. Although no change in fractal dimension was observed as a result of application of the test solution containing only 25

  13. Seroprevalence and parasite load of Toxoplasma gondii in Mexican hairless pig (Sus scrofa) tissues from the Southeast of Mexico.

    PubMed

    Dzib-Paredes, G F; Rosado-Aguilar, J A; Acosta-Viana, K Y; Ortega-Pacheco, A; Hernández-Cortázar, I B; Guzman-Marín, E; Jiménez-Coello, M

    2016-10-15

    This study aimed to estimate the seroprevalence and determine the parasite load of Toxoplasma gondii (T. gondii) in the heart and tongue tissues and the semimembranosus/gracilis muscles in a population of Mexican hairless pig (MHP). A cross-sectional study was conducted in 81 MHP, 9-12 weeks of age, from 10 municipalities in Yucatan, Mexico. The prevalence was estimated by the detection of T. gondii IgG antibodies via an indirect ELISA assay. The parasite burden was also determined by testing genomic DNA from sampled tissues using quantitative real-time PCR (qPCR), which amplified a 62bp product from the B1 gene of T. gondii. The seroprevalence was 53% (43/81), ranging from 0 to 100% seropositivity rate depending on the municipalitie of origin. The qPCR allowed detection of T. gondii in 5.3% (9/168) of the tissue samples, with an average of 2.5±2.71 parasites per gram (0.17±0.18 parasite equivalent) for the leg muscle tissue, 0.26±0.39 (0.01±0.02 parasite equivalent) for the heart tissue and 0.31±0.37 (0.021±0.025 parasite equivalent) for the tongue tissue. No significant difference (p>0.05) was observed in the proportion and parasite burden among the different types of tissues evaluated. As shown by the ELISA, a high seroprevalence of T. gondii exists in MHP from the Yucatán Peninsula. The parasite burden found in the tissues showed similar tropism; therefore, the consumption of these tissues involves the same risk of acquiring infection if not properly cooked.

  14. Recent Southeast Asian domestication and Lapita dispersal of sacred male pseudohermaphroditic “tuskers” and hairless pigs of Vanuatu

    PubMed Central

    Lum, J. Koji; McIntyre, James K.; Greger, Douglas L.; Huffman, Kirk W.; Vilar, Miguel G.

    2006-01-01

    Recent analyses of global pig populations revealed strict correlations between mtDNA phylogenies and geographic locations. An exception was the monophyletic “Pacific clade” (PC) of pigs not previously linked to any specific location. We examined mtDNA sequences of two varieties of Vanuatu sacred pigs, the male pseudohermaphroditic Narave from the island of Malo (n = 9) and the hairless Kapia from the island of Tanna (n = 9), as well as control pigs (n = 21) from the islands of Malo, Tanna, and Epi and compared them with GenBank sequences to determine (i) the distribution of PC and introduced domestic lineages within Vanuatu, (ii) relationship between the Narave and Kapia, and (iii) origin of the PC. All of the Narave share two PC mtDNA sequences, one of which matches the sequence of a Narave collected in 1927, consistent with an unbroken maternal descent of these intersex pigs from the original pigs brought to Vanuatu 3,200 years ago. One-third of the Kapia share a single PC lineage also found in the Narave. The remaining Kapia lineages are associated with recently introduced, globally distributed domestic breeds. The predominant Narave lineage is also shared with two wild boars from Vietnam. These data suggest that PC pigs were recently domesticated within Southeast Asia and dispersed during the human colonization of Remote Oceania associated with the Lapita cultural complex. More extensive sampling of Southeast Asian wild boar diversity may refine the location of Pacific pig domestication and potentially the proximate homeland of the Lapita cultural complex. PMID:17088556

  15. Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin

    SciTech Connect

    Jain, Anil K.; Tewari-Singh, Neera; Inturi, Swetha; Kumar, Dileep; Orlicky, David J.; Agarwal, Chapla; White, Carl W.; Agarwal, Rajesh

    2015-05-15

    Currently, there is no effective antidote to prevent skin injuries by sulfur mustard (SM) and nitrogen mustard (NM), which are vesicating agents with potential relevance to chemical warfare, terrorist attacks, or industrial/laboratory accidents. Our earlier report has demonstrated the therapeutic efficacy of silibinin, a natural flavanone, in reversing monofunctional alkylating SM analog 2-chloroethyl ethyl sulfide-induced toxic effects in mouse skin. To translate this effect to a bifunctional alkylating vesicant, herein, efficacy studies were carried out with NM. Topical application of silibinin (1 or 2 mg) 30 min after NM exposure on the dorsal skin of male SKH-1 hairless mice significantly decreased NM-induced toxic lesions at 24, 72 or 120 h post-exposure. Specifically, silibinin treatment resulted in dose-dependent reduction of NM-induced increase in epidermal thickness, dead and denuded epidermis, parakeratosis and microvesication. Higher silibinin dose also caused a 79% and 51%reversal in NM-induced increases in myeloperoxidase activity and COX-2 levels, respectively. Furthermore, silibinin completely prevented NM-induced H2A.X phosphorylation, indicating reversal of DNA damage which could be an oxidative DNA damage as evidenced by high levels of 8-oxodG in NM-exposed mouse skin that was significantly reversed by silibinin. Together, these findings suggest that attenuation of NM-induced skin injury by silibinin is due to its effects on the pathways associated with DNA damage, inflammation, vesication and oxidative stress. In conclusion, results presented here support the optimization of silibinin as an effective treatment of skin injury by vesicants. - Highlights: • Silibinin treatment attenuated nitrogen mustard (NM)-induced skin injury. • Silibinin affects pathways associated with DNA damage, inflammation and vesication. • The efficacy of silibinin could also be associated with oxidative stress. • These results support testing and optimization of

  16. Activation of Peroxisome Proliferator-Activated Receptor Alpha Improves Aged and UV-Irradiated Skin by Catalase Induction

    PubMed Central

    Shin, Mi Hee; Lee, Se-Rah; Kim, Min-Kyoung; Shin, Chang-Yup

    2016-01-01

    Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear hormone receptor involved in the transcriptional regulation of lipid metabolism, fatty acid oxidation, and glucose homeostasis. Its activation stimulates antioxidant enzymes such as catalase, whose expression is decreased in aged human skin. Here we investigated the expression of PPARα in aged and ultraviolet (UV)-irradiated skin, and whether PPARα activation can modulate expressions of matrix metalloproteinase (MMP)-1 and procollagen through catalase regulation. We found that PPARα mRNA level was significantly decreased in intrinsically aged and photoaged human skin as well as in UV-irradiated skin. A PPARα activator, Wy14643, inhibited UV-induced increase of MMP-1 and decrease of procollagen expression and caused marked increase in catalase expression. Furthermore, production of reactive oxygen species (ROS) was suppressed by Wy14643 in UV-irradiated and aged dermal fibroblasts, suggesting that the PPARα activation-induced upregulation of catalase leads to scavenging of ROS produced due to UV irradiation or aging. PPARα knockdown decreased catalase expression and abolished the beneficial effects of Wy14643. Topical application of Wy14643 on hairless mice restored catalase activity and prevented MMP-13 and inflammatory responses in skin. Our findings indicate that PPARα activation triggers catalase expression and ROS scavenging, thereby protecting skin from UV-induced damage and intrinsic aging. PMID:27611371

  17. Hesperidin methyl chalcone inhibits oxidative stress and inflammation in a mouse model of ultraviolet B irradiation-induced skin damage.

    PubMed

    Martinez, Renata M; Pinho-Ribeiro, Felipe A; Steffen, Vinicius S; Caviglione, Carla V; Vignoli, Josiane A; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rubia

    2015-07-01

    Hesperidin methyl chalcone (HMC) is a safe flavonoid used to treat chronic venous diseases, but its effects and mechanisms on UVB irradiation-induced inflammation and oxidative stress have never been described in vivo. Thus, the purpose of this study was to evaluate the effects of systemic administration of HMC in skin oxidative stress and inflammation induced by UVB irradiation. To induce skin damage, hairless mice were exposed to an acute UVB irradiation dose of 4.14 J/cm(2), and the dorsal skin samples were collected to evaluate oxidative stress and inflammatory response. The intraperitoneal treatment with HMC at the dose of 300 mg/kg inhibited UVB irradiation-induced skin edema, neutrophil recruitment, and matrix metalloproteinase-9 activity. HMC also protected the skin from UVB irradiation-induced oxidative stress by maintaining ferric reducing antioxidant power (FRAP), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS) scavenging ability and antioxidant levels (reduced glutathione and catalase). Corroborating, HMC inhibited UVB irradiation-induced superoxide anion generation and gp91phox (NADPH oxidase subunit) mRNA expression. Furthermore, the antioxidant effect of HMC resulted in lower production of inflammatory mediators, including lipid hydroperoxides and a wide range of cytokines. Taken together, these results unveil a novel applicability of HMC in the treatment of UVB irradiation-induced skin inflammation and oxidative stress.

  18. Skin Barrier Recovery by Protease-Activated Receptor-2 Antagonist Lobaric Acid

    PubMed Central

    Joo, Yeon Ah; Chung, Hyunjin; Yoon, Sohyun; Park, Jong Il; Lee, Ji Eun; Myung, Cheol Hwan; Hwang, Jae Sung

    2016-01-01

    Atopic dermatitis (AD) results from gene and environment interactions that lead to a range of immunological abnormalities and breakdown of the skin barrier. Protease-activated receptor 2 (PAR2) belongs to a family of G-protein coupled receptors and is expressed in suprabasal layers of the epidermis. PAR2 is activated by both trypsin and a specific agonist peptide, SLIGKV-NH2 and is involved in both epidermal permeability barrier homeostasis and epithelial inflammation. In this study, we investigated the effect of lobaric acid on inflammation, keratinocyte differentiation, and recovery of the skin barrier in hairless mice. Lobaric acid blocked trypsin-induced and SLIGKV-NH2-induced PAR2 activation resulting in decreased mobilization of intracellular Ca2+ in HaCaT keratinocytes. Lobaric acid reduced expression of interleukin-8 induced by SLIGKV-NH2 and thymus and activation regulated chemokine (TARC) induced by tumor necrosis factor-a (TNF-α) and IFN-γ in HaCaT keratinocytes. Lobaric acid also blocked SLIGKV-NH2-induced activation of ERK, which is a downstream signal of PAR2 in normal human keratinocytes (NHEKs). Treatment with SLIGKV-NH2 downregulated expression of involucrin, a differentiation marker protein in HaCaT keratinocytes, and upregulated expression of involucrin, transglutamase1 and filaggrin in NHEKs. However, lobaric acid antagonized the effect of SLIGKV-NH2 in HaCaT keratinocytes and NHEKs. Topical application of lobaric acid accelerated barrier recovery kinetics in a SKH-1 hairless mouse model. These results suggested that lobaric acid is a PAR2 antagonist and could be a possible therapeutic agent for atopic dermatitis. PMID:27169822

  19. Stages of Skin Cancer

    MedlinePlus

    ... Skin Cancer Skin color and being exposed to sunlight can increase the risk of nonmelanoma skin cancer ... carcinoma include the following: Being exposed to natural sunlight or artificial sunlight (such as from tanning beds) ...

  20. Skin Cancer Treatment

    MedlinePlus

    ... Skin Cancer Skin color and being exposed to sunlight can increase the risk of nonmelanoma skin cancer ... carcinoma include the following: Being exposed to natural sunlight or artificial sunlight (such as from tanning beds) ...

  1. Basal cell skin cancer

    MedlinePlus

    ... occur on skin that is regularly exposed to sunlight or other ultraviolet radiation. This type of skin ... skin cancer is to reduce your exposure to sunlight . Always use sunscreen: Apply sunscreen with sun protection ...

  2. Skin Condition Finder

    MedlinePlus

    ... SKIN CONDITIONS HEALTH TOPICS FOR PROFESSIONALS Rash and Skin Condition Finder 1 Select Age Group Infant Child ... Toe Toe Webspace Toe Nail CLOSE About the Skin Condition Finder Have a health question or concern? ...

  3. Skin Complications of IBD

    MedlinePlus

    ... Home > Resources > Skin Complications of IBD Go Back Skin Complications of IBD Email Print + Share After arthritis, ... about 5% of people with inflammatory bowel disease. SKIN DISORDERS COMMONLY SEEN IN IBD ERHTHEMA NODOSUM The ...

  4. Scalded skin syndrome

    MedlinePlus

    Ritter disease; Staphylococcal scalded skin syndrome (SSS) ... Scalded skin syndrome (SSS) is caused by infection with certain strains of Staphylococcus bacteria. The bacteria produce a toxin that causes the skin ...

  5. Skin Allergy Quiz

    MedlinePlus

    ... time. Some common medications that can cause skin allergy include penicillin, sulfa drugs, barbiturates and anticonvulsants just to mention a few. Some of the symptoms from drug allergies might be hives, skin rash, itchy skin or ...

  6. Learning about Skin Cancer

    MedlinePlus

    ... Why Deadly Skin Cancers Spread 2000 News Release Learning About Skin Cancer What are the most common ... skin surface. When a melanoma becomes thick and deep, the disease often spreads to other parts of ...

  7. The effects of topical and oral L-selenomethionine on pigmentation and skin cancer induced by ultraviolet irradiation.

    PubMed

    Burke, K E; Combs, G F; Gross, E G; Bhuyan, K C; Abu-Libdeh, H

    1992-01-01

    This study was conducted to determine whether oral and/or topical selenium (Se) supplementation can reduce the incidence of acute and/or chronic damage to the skin (i.e., sunburn and pigmentation and/or skin cancer, respectively) induced by ultraviolet (UV) irradiation in mice. Groups of 38 BALB:c female mice or 16 Skh:2 hairless pigmented mice were treated with 1) lotion vehicle, 2) 0.02% L-selenomethionine (SeMet) lotion, or 3) vehicle and 1.5 ppm SeMet in the drinking water. Within each group, 30 BALB:c mice or 12 Skh:2 mice were given UV irradiation (Westinghouse FS 40 bulbs) three times per week in doses of 0.575 and 0.24 J/cm2, respectively. The animals' weights and food intakes and the Se concentrations of skin and liver were measured. Skin biopsies were taken from the backs and abdomens of all animals to evaluate the relative amounts of Se and the damage by UV irradiation. Skin pigmentation was scored, and the total number of clinically detectable skin tumors per animal was counted weekly. Results showed that the skin Se concentrations in areas of application of the lotion containing SeMet were greater than those of animals given comparable oral doses, while the Se concentrations of untreated skin and liver were similar to those of animals receiving oral Se. Mice treated with Se showed no signs of toxicity and had significantly less skin damage by UV irradiation, as indicated by reduced inflammation and pigmentation and by later onset and lesser incidence of skin cancer.

  8. Lgr6+ stem cells and their progeny in mouse epidermis under regimens of exogenous skin carcinogenesis, and their absence in ensuing skin tumors

    PubMed Central

    van de Glind, Gerline C.; Rebel, Heggert G.; Out-Luiting, Jacoba J.; Zoutman, Wim; Tensen, Cornelis P.; de Gruijl, Frank R.

    2016-01-01

    Lgr6+ cells have been identified as a novel class of proliferating (Ki67+) stem cells in mouse epidermis. We investigated their response to UV exposure in Lgr6-EGFP-Ires-CreERT2/R26R-LacZ haired and hairless mice and whether they become initiating cells of UV- or chemically induced skin tumors. UV overexposure erased Lgr6+ cells (EGFP+) from the interfollicular epidermis (IFE), but - as after wounding - they apparently repopulated the IFE from the hair follicles. Under sub-sunburn chronic UV exposure, Lgr6+ cells and their progeny (LacZ+ after pulse of tamoxifen) diminished strongly in the IFE. Although the inter-tumoral IFE clearly showed Lgr6 progeny, none of the UV- or chemically induced tumors (n = 22 and 41, respectively) appeared to be clonal expansions of Lgr6+ stem cells; i.e. no Lgr6+ cells or progeny in the proliferating tumor bulk. In checking for promoter methylation we found it to occur stochastically for the EGFP-Cre cassette. Lgr6 mRNA measured by qPCR was found to be diminished in skin tumors (also in UV tumors from wt type mice). The ratio of Lgr6/Ki67 was significantly reduced, pointing at a loss of Lgr6+ cells from the proliferative pool. Our data show that Lgr6+ cells are not major tumor-initiating cells in skin carcinogenesis. PMID:27880932

  9. Skin to skin care:heat balance.

    PubMed Central

    Karlsson, H

    1996-01-01

    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. PMID:8949698

  10. BASIS FOR ENHANCED BARRIER FUNCTION OF PIGMENTED SKIN

    PubMed Central

    Man, Mao-Qiang; Lin, Tzu-Kai; Santiago, Juan Luis; Celli, Anna; Zhong, Lily; Huang, Zhi-Ming; Roelandt, Truus; Hupe, Melanie; Sundberg, John P.; Silva, Kathleen A.; Crumrine, Debra; Martin-Ezquerra, Gemma; Trullas, Carles; Sun, Richard; Wakefield, Joan S.; Wei, Maria L.; Feingold, Kenneth R.; Mauro, Theodora M.; Elias, Peter M.

    2014-01-01

    Humans with darkly-pigmented skin display superior permeability barrier function in comparison to humans with lightly-pigmented skin. The reduced pH of the stratum corneum (SC) of darkly-pigmented skin could account for enhanced function, because acidifying lightly-pigmented human SC resets barrier function to darkly-pigmented levels. In SKH1 (non-pigmented) vs. SKH2/J (pigmented) hairless mice, we evaluated how a pigment-dependent reduction in pH could influence epidermal barrier function. Permeability barrier homeostasis is enhanced in SKH2/J vs. SKH1 mice, correlating with a reduced pH in the lower SC that co-localizes with the extrusion of melanin granules. Darkly-pigmented human epidermis also shows substantial melanin extrusion in the outer epidermis. Both acute barrier disruption and topical basic pH challenges accelerate re-acidification of SKH2/J (but not SKH1) SC, while inducing melanin extrusion. SKH2/J mice also display enhanced expression of the SC acidifying enzyme, secretory phospholipase A2f (sPLA2f). Enhanced barrier function of SKH2/J mice could be attributed to enhanced activity of two acidic pH-dependent, ceramide-generating enzymes, β-glucocerebrosidase and acidic sphingomyelinase, leading to accelerated maturation of SC lamellar bilayers. Finally, organotypic cultures of darkly-pigmented-bearing human keratinocytes display enhanced barrier function in comparison to lightly-pigmented cultures. Together, these results suggest that the superior barrier function of pigmented epidermis can be largely attributed to the pH-lowering impact of melanin persistence/extrusion and enhanced sPLA2f expression. PMID:24732399

  11. Skin Care and Aging

    MedlinePlus

    ... version of this page please turn Javascript on. Skin Care and Aging How Aging Affects Skin Your skin changes with age. It becomes thinner, ... to make it feel and look better. Dry Skin and Itching Click for more information Many older ...

  12. Acne in ethnic skin.

    PubMed

    Halder, Rebat M; Brooks, Howard L; Callender, Valerie D

    2003-10-01

    Acne is the most common disorder observed in ethnic skin. Clinical presentation is different than in white skin. Postinflammatory hyperpigmentation is a common sequelae of acne in darker skin. The management of acne in ethnic skin is based largely on the prevention and treatment of hyperpigmentation.

  13. Evaluation of physicochemical properties, skin permeation and accumulation profiles of salicylic acid amide prodrugs as sunscreen agent.

    PubMed

    Yan, Yi-Dong; Sung, Jun Ho; Lee, Dong Won; Kim, Jung Sun; Jeon, Eun-Mi; Kim, Dae-Duk; Kim, Dong Wuk; Kim, Jong Oh; Piao, Ming Guan; Li, Dong Xun; Yong, Chul Soon; Choi, Han Gon

    2011-10-31

    Various amide prodrugs of salicylic acid were synthesised, and their physicochemical properties including lipophilicity, chemical stability and enzymatic hydrolysis were investigated. In vivo skin permeation and accumulation profiles were also evaluated using a combination of common permeation enhancing techniques such as the use of a supersaturated solution of permeants in an enhancer vehicle, a lipophilic receptor solution, removal of the stratum corneum and delipidisation of skin. Their capacity factor values were proportional to the degree of carbon-carbon saturation in the side chain. All these amides were highly stable in acetonitrile and glycerine. Amide prodrugs were converted to salicylic acid both in hairless mouse liver and skin homogenates. N-dodecyl salicylamide (C12SM) showed the lowest permeation of salicylic acid in skin compared to the other prodrugs, probably due to its low aqueous solubility. It had a high affinity for the stratum corneum and its accumulation was restricted to only the uppermost layer of skin. Thus, this amide prodrug could be a safer topical sunscreen agent with minimum potential for systemic absorption.

  14. In vivo iontophoretic delivery of salmon calcitonin across microporated skin.

    PubMed

    Vemulapalli, Viswatej; Bai, Yun; Kalluri, Haripriya; Herwadkar, Anushree; Kim, Hyun; Davis, Shawn P; Friden, Phil M; Banga, Ajay K

    2012-08-01

    The purpose of this study was to determine the effect of microneedle (MN) technology and its combination with iontophoresis (ITP) on the in vivo transdermal delivery of salmon calcitonin (sCT). Maltose MNs (500 µm) were used to porate skin prior to application of the drug, with or without ITP. Micropores created by maltose MNs were characterized by histological sectioning and calcein imaging studies, which indicated uniformity of the created micropores. In vivo studies were performed in hairless rats to assess the degree of enhancement achieved by ITP (0.2 mA/cm² for 1 h), MNs (81 MNs), and their combination. In vivo studies indicate a serum maximal concentration of 0.61 ± 0.42 ng/mL, 1.79 ± 0.72 ng/mL, and 5.51 ± 0.32 ng/mL for ITP, MNs, and combination treatment, respectively. MN treatment alone increased serum concentration 2.5-fold and the combination treatment increased the concentration ninefold as compared with iontophoretic treatment alone. Combination treatment of ITP and MNs resulted in the highest delivery of sCT and therapeutic levels were achieved within 5 min of administration.

  15. Blackberry extract inhibits UVB-induced oxidative damage and inflammation through MAP kinases and NF-κB signaling pathways in SKH-1 mice skin

    SciTech Connect

    Divya, Sasidharan Padmaja; Wang, Xin; Pratheeshkumar, Poyil; Son, Young-Ok; Roy, Ram Vinod; Kim, Donghern; Dai, Jin; Hitron, John Andrew; Wang, Lei; Asha, Padmaja; Shi, Xianglin; Zhang, Zhuo

    2015-04-01

    Extensive exposure of solar ultraviolet-B (UVB) radiation to skin induces oxidative stress and inflammation that play a crucial role in the induction of skin cancer. Photochemoprevention with natural products represents a simple but very effective strategy for the management of cutaneous neoplasia. In this study, we investigated whether blackberry extract (BBE) reduces chronic inflammatory responses induced by UVB irradiation in SKH-1 hairless mice skin. Mice were exposed to UVB radiation (100 mJ/cm{sup 2}) on alternate days for 10 weeks, and BBE (10% and 20%) was applied topically a day before UVB exposure. Our results show that BBE suppressed UVB-induced hyperplasia and reduced infiltration of inflammatory cells in the SKH-1 hairless mice skin. BBE treatment reduced glutathione (GSH) depletion, lipid peroxidation (LPO), and myeloperoxidase (MPO) in mouse skin by chronic UVB exposure. BBE significantly decreased the level of pro-inflammatory cytokines IL-6 and TNF-α in UVB-exposed skin. Likewise, UVB-induced inflammatory responses were diminished by BBE as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases, Erk1/2, p38, JNK1/2 and MKK4. Furthermore, BBE also reduced inflammatory mediators such as cyclooxygenase-2 (COX-2), prostaglandin E{sub 2} (PGE{sub 2}), and inducible nitric oxide synthase (iNOS) levels in UVB-exposed skin. Treatment with BBE inhibited UVB-induced nuclear translocation of NF-κB and degradation of IκBα in mouse skin. Immunohistochemistry analysis revealed that topical application of BBE inhibited the expression of 8-oxo-7, 8-dihydro-2′-deoxyguanosine (8-oxodG), cyclobutane pyrimidine dimers (CPD), proliferating cell nuclear antigen (PCNA), and cyclin D1 in UVB-exposed skin. Collectively, these data indicate that BBE protects from UVB-induced oxidative damage and inflammation by modulating MAP kinase and NF-κB signaling pathways. - Highlights: • Blackberry extract inhibits UVB-induced glutathione depletion.

  16. Estrogens and aging skin

    PubMed Central

    Thornton, M. Julie

    2013-01-01

    Estrogen deficiency following menopause results in atrophic skin changes and acceleration of skin aging. Estrogens significantly modulate skin physiology, targeting keratinocytes, fibroblasts, melanocytes, hair follicles and sebaceous glands, and improve angiogenesis, wound healing and immune responses. Estrogen insufficiency decreases defense against oxidative stress; skin becomes thinner with less collagen, decreased elasticity, increased wrinkling, increased dryness and reduced vascularity. Its protective function becomes compromised and aging is associated with impaired wound healing, hair loss, pigmentary changes and skin cancer.   Skin aging can be significantly delayed by the administration of estrogen. This paper reviews estrogen effects on human skin and the mechanisms by which estrogens can alleviate the changes due to aging. The relevance of estrogen replacement, selective estrogen receptor modulators (SERMs) and phytoestrogens as therapies for diminishing skin aging is highlighted. Understanding estrogen signaling in skin will provide a basis for interventions in aging pathologies. PMID:24194966

  17. Separation of retinoid-induced epidermal and dermal thickening from skin irritation.

    PubMed

    Varani, James; Fligiel, Helene; Zhang, Jian; Aslam, Muhammad Nadeem; Lu, Yi; Dehne, Lindsay A; Keller, Evan T

    2003-11-01

    The ability of the synthetic retinoid MDI-301, in which the carboxylic acid of 9- cis-retinoic acid (9-cis-RA) is replaced with an ester linkage, to induce epidermal and dermal thickening and skin irritation (erythema and flaking) in hairless (rhino) mice following its topical application was investigated in comparison with that of 14-all- trans-retinoic acid (14-all-trans-RA) and 9-cis-RA. MDI-301 induced epidermal proliferation leading to a thickened epidermis. Treated animals also demonstrated a prominent band of organized connective tissue immediately below the epidermis. In its ability to induce epidermal thickening, MDI-301 was quantitatively similar to 14-all-trans-RA and 9-cis-RA. However, unlike 14-all-trans-RA and 9-cis-RA, which produced skin irritation associated with a perivascular influx of mononuclear leukocytes into the dermis, there was no evidence of irritation with MDI-301 and little leukocyte infiltration. Intraperitoneal injection of either 14-all-trans-RA or MDI-301 also resulted in epidermal and dermal thickening. Irritation of skin was not observed in these animals but splenomegaly was prominent in animals treated with either agent.

  18. Topical apigenin improves epidermal permeability barrier homoeostasis in normal murine skin by divergent mechanisms.

    PubMed

    Hou, Maihua; Sun, Richard; Hupe, Melanie; Kim, Peggy L; Park, Kyungho; Crumrine, Debra; Lin, Tzu-Kai; Santiago, Juan Luis; Mauro, Theodora M; Elias, Peter M; Man, Mao-Qiang

    2013-03-01

    The beneficial effects of certain herbal medicines on cutaneous function have been appreciated for centuries. Among these agents, chrysanthemum extract, apigenin, has been used for skin care, particularly in China, for millennia. However, the underlying mechanisms by which apigenin benefits the skin are not known. In this study, we first determined whether topical apigenin positively influences permeability barrier homoeostasis, and then the basis thereof. Hairless mice were treated topically with either 0.1% apigenin or vehicle alone twice daily for 9 days. At the end of the treatments, permeability barrier function was assessed with either an electrolytic water analyzer or a Tewameter. Our results show that topical apigenin significantly enhanced permeability barrier homoeostasis after tape stripping, although basal permeability barrier function remained unchanged. Improved barrier function correlated with enhanced filaggrin expression and lamellar body production, which was paralleled by elevated mRNA levels for the epidermal ABCA12. The mRNA levels for key lipid synthetic enzymes also were upregulated by apigenin. Finally, both cathelicidin-related peptide and mouse beta-defensin 3 immunostaining were increased by apigenin. We conclude that topical apigenin improves epidermal permeability barrier function by stimulating epidermal differentiation, lipid synthesis and secretion, as well as cutaneous antimicrobial peptide production. Apigenin could be useful for the prevention and treatment of skin disorders characterized by permeability barrier dysfunction, associated with reduced filaggrin levels and impaired antimicrobial defenses, such as atopic dermatitis.

  19. Development of a codrug approach for sustained drug delivery across microneedle-treated skin.

    PubMed

    Ghosh, Priyanka; Pinninti, Raghotham R; Hammell, Dana C; Paudel, Kalpana S; Stinchcomb, Audra L

    2013-05-01

    Microneedle (MN) enhanced transdermal drug delivery enables the transport of a host of molecules that cannot be delivered across the skin by passive diffusion alone. However, the skin being a self-regenerating organ heals itself and thus prevents delivery of molecules through micropores for a 7-day time period, the ideal transdermal delivery goal. Hence, it is necessary to employ a second drug molecule, a cyclooxygenase inhibitor to enhance pore lifetime by decreasing local subclinical inflammatory response following MN treatment. A codrug approach using a 3-O-ester codrug of the model drug naltrexone (NTX) with diclofenac (DIC), a cyclooxygenase inhibitor, was tested in vitro as well as in vivo to look at stability, bioconversion and permeation. The results indicated that the approach could be useful for transdermal drug delivery of NTX from a single patch for a week, but stability and solubility optimization will be required for the codrug before it can deliver significant levels of NTX into the plasma. The skin concentration of DIC was high enough to keep the pores open in vivo in a hairless guinea pig model as demonstrated by day seven pore visualization studies.

  20. Germicidal Efficacy and Mammalian Skin Safety of 222-nm UV Light.

    PubMed

    Buonanno, Manuela; Ponnaiya, Brian; Welch, David; Stanislauskas, Milda; Randers-Pehrson, Gerhard; Smilenov, Lubomir; Lowy, Franklin D; Owens, David M; Brenner, David J

    2017-04-01

    We have previously shown that 207-nm ultraviolet (UV) light has similar antimicrobial properties as typical germicidal UV light (254 nm), but without inducing mammalian skin damage. The biophysical rationale is based on the limited penetration distance of 207-nm light in biological samples (e.g. stratum corneum) compared with that of 254-nm light. Here we extended our previous studies to 222-nm light and tested the hypothesis that there exists a narrow wavelength window in the far-UVC region, from around 200-222 nm, which is significantly harmful to bacteria, but without damaging cells in tissues. We used a krypton-chlorine (Kr-Cl) excimer lamp that produces 222-nm UV light with a bandpass filter to remove the lower- and higher-wavelength components. Relative to respective controls, we measured: 1. in vitro killing of methicillin-resistant Staphylococcus aureus (MRSA) as a function of UV fluence; 2. yields of the main UV-associated premutagenic DNA lesions (cyclobutane pyrimidine dimers and 6-4 photoproducts) in a 3D human skin tissue model in vitro; 3. eight cellular and molecular skin damage endpoints in exposed hairless mice in vivo. Comparisons were made with results from a conventional 254-nm UV germicidal lamp used as positive control. We found that 222-nm light kills MRSA efficiently but, unlike conventional germicidal UV lamps (254 nm), it produces almost no premutagenic UV-associated DNA lesions in a 3D human skin model and it is not cytotoxic to exposed mammalian skin. As predicted by biophysical considerations and in agreement with our previous findings, far-UVC light in the range of 200-222 nm kills bacteria efficiently regardless of their drug-resistant proficiency, but without the skin damaging effects associated with conventional germicidal UV exposure.

  1. Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin.

    PubMed

    Jain, Anil K; Tewari-Singh, Neera; Inturi, Swetha; Kumar, Dileep; Orlicky, David J; Agarwal, Chapla; White, Carl W; Agarwal, Rajesh

    2015-05-15

    Currently, there is no effective antidote to prevent skin injuries by sulfur mustard (SM) and nitrogen mustard (NM), which are vesicating agents with potential relevance to chemical warfare, terrorist attacks, or industrial/laboratory accidents. Our earlier report has demonstrated the therapeutic efficacy of silibinin, a natural flavanone, in reversing monofunctional alkylating SM analog 2-chloroethyl ethyl sulfide-induced toxic effects in mouse skin. To translate this effect to a bifunctional alkylating vesicant, herein, efficacy studies were carried out with NM. Topical application of silibinin (1 or 2mg) 30 min after NM exposure on the dorsal skin of male SKH-1 hairless mice significantly decreased NM-induced toxic lesions at 24, 72 or 120 h post-exposure. Specifically, silibinin treatment resulted in dose-dependent reduction of NM-induced increase in epidermal thickness, dead and denuded epidermis, parakeratosis and microvesication. Higher silibinin dose also caused a 79% and 51%reversal in NM-induced increases in myeloperoxidase activity and COX-2 levels, respectively. Furthermore, silibinin completely prevented NM-induced H2A.X phosphorylation, indicating reversal of DNA damage which could be an oxidative DNA damage as evidenced by high levels of 8-oxodG in NM-exposed mouse skin that was significantly reversed by silibinin. Together, these findings suggest that attenuation of NM-induced skin injury by silibinin is due to its effects on the pathways associated with DNA damage, inflammation, vesication and oxidative stress. In conclusion, results presented here support the optimization of silibinin as an effective treatment of skin injury by vesicants.

  2. Flavanone silibinin treatment attenuates nitrogen mustard-induced toxic effects in mouse skin

    PubMed Central

    Jain, Anil K; Tewari-Singh, Neera; Inturi, Swetha; Kumar, Dileep; Orlicky, David J; Agarwal, Chapla; White, Carl W; Agarwal, Rajesh

    2015-01-01

    Currently, there is no effective antidote to prevent skin injuries by sulfur mustard (SM) and nitrogen mustard (NM), which are vesicating agents with potential relevance to chemical warfare, terrorist attacks, or industrial/laboratory accidents. Our earlier report has demonstrated the therapeutic efficacy of silibinin, a natural flavanone, in reversing monofunctional alkylating SM analog 2-chloroethyl ethyl sulfide-induced toxic effects in mouse skin. To translate this effect to a bifunctional alkylating vesicant, herein, efficacy studies were carried out with NM. Topical application of silibinin (1 or 2 mg) 30 min after NM exposure on the dorsal skin of male SKH-1 hairless mice significantly decreased NM-induced toxic lesions at 24, 72 or 120 h post-exposure. Specifically, silibinin treatment resulted in dose-dependent reduction of NM-induced increase in epidermal thickness, dead and denuded epidermis, parakeratosis and microvesication. Higher silibinin dose also caused a 79% and 51% reversal in NM-induced increases in myeloperoxidase activity and COX-2 levels, respectively. Furthermore, silibinin completely prevented NM-induced H2A.X phosphorylation, indicating reversal of DNA damage which could be an oxidative DNA damage as evidenced by high levels of 8-oxodG in NM-exposed mouse skin that was significantly reversed by silibinin. Together, these findings suggest that attenuation of NM-induced skin injury by silibinin is due to its effects on the pathways associated with DNA damage, inflammation, vesication and oxidative stress. In conclusion, results presented here support the optimization of silibinin as an effective treatment of skin injury by vesicants. PMID:25791923

  3. A synthetic C16 omega-hydroxyphytoceramide improves skin barrier functions from diversely perturbed epidermal conditions.

    PubMed

    Oh, Myoung Jin; Nam, Jin Ju; Lee, Eun Ok; Kim, Jin Wook; Park, Chang Seo

    2016-10-01

    Omega-hydroxyceramides (ω-OH-Cer) play a crucial role in maintaining the integrity of skin barrier. ω-OH-Cer are the primary lipid constituents of the corneocyte lipid envelope (CLE) covalently attached to the outer surface of the cornified envelope linked to involucrin to become bound form lipids in stratum corneum (SC). CLE becomes a hydrophobic impermeable layer of matured corneocyte preventing loss of natural moisturizing factor inside the corneocytes. More importantly, CLE may also play an important role in the formation of proper orientation of intercellular lipid lamellar structure by interdigitating with the intercellular lipids in a comb-like fashion. Abnormal barrier conditions associated with atopic dermatitis but also UVB-irradiated skins are known to have lowered level of bound lipids, especially ω-OH-Cer, which indicate that ω-OH-Cer play an important role in maintaining the integrity of skin barrier. In this study, protective effects of a novel synthetic C16 omega-hydroxyphytoceramides (ω-OH-phytoceramide) on skin barrier function were investigated. Epidermal barrier disruption was induced by UVB irradiation, tape-stripping in hairless mouse and human skin. Protective effect of damaged epidermis was evaluated using the measurement of transepidermal water loss and cohesion of SC. Increased keratinocyte differentiation was verified using cultured keratinocyte through western blot. Results clearly demonstrated that a synthetic C16 ω-OH-phytoceramide enhanced the integrity of SC and accelerated the recovery of damaged skin barrier function by stimulating differentiation process. In a conclusion, a synthetic C16 ω-OH-phytoceramide treatment improved epidermal homeostasis in several disrupted conditions.

  4. Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti-cholinergic agent against skin injury induced by sulfur mustard

    SciTech Connect

    Chang, Yoke-Chen; Wang, James D.; Hahn, Rita A.; Gordon, Marion K.; Joseph, Laurie B.; Heck, Diane E.; Heindel, Ned D.; Young, Sherri C.; Sinko, Patrick J.; Casillas, Robert P.; Laskin, Jeffrey D.; Laskin, Debra L.; Gerecke, Donald R.

    2014-10-15

    Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 h post-SM exposure. After 96 h, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermal–epidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure. - Highlights: • Bifunctional anti-inflammatory prodrug (NDH4338) tested on SM exposed mouse skin • The prodrug NDH4338 was designed to target COX2 and acetylcholinesterase. • The application of NDH4338 improved cutaneous wound repair after SM induced injury. • NDH4338 treatment demonstrated a reduction in COX2 expression on SM injured skin. • Changes of skin repair

  5. The Genetics of a Small Autosomal Region of DROSOPHILA MELANOGASTER Containing the Structural Gene for Alcohol Dehydrogenase. III. Hypomorphic and Hypermorphic Mutations Affecting the Expression of Hairless

    PubMed Central

    Ashburner, Michael

    1982-01-01

    A lethal locus (l(2)br7;35B6-10), near Adh on chromosome arm 2L of D. melanogaster, is identified with Plunkett's dominant suppressor of Hairless (H). Of eight new alleles, seven act as dominant suppressors of H, the eighth is a dominant enhancer of H. One of the suppressor alleles is both a leaky lethal and a weak suppressor of H. Confirming Nash (1970), deletions of l(2)br7 are dominant suppressors, and duplications are dominant enhancers of H. A simple model is proposed to account for the interaction of l(2)br7 and H, assuming that amorphic (or hypomorphic) alleles of l(2)br7 suppress H and that hypermorphic alleles enhance H. PMID:6816670

  6. Sirolimus reduces the incidence and progression of UVB-induced skin cancer in SKH mice even with co-administration of cyclosporine A.

    PubMed

    Wulff, Brian C; Kusewitt, Donna F; VanBuskirk, Anne M; Thomas-Ahner, Jennifer M; Duncan, F Jason; Oberyszyn, Tatiana M

    2008-10-01

    Transplant immunosuppressants have been implicated in the increased incidence of non-melanoma skin cancer in transplant recipients, most of whom harbor considerable UVB-induced DNA damage in their skin prior to transplantation. This study was designed to evaluate the effects of two commonly used immunosuppressive drugs, cyclosporine A (CsA) and sirolimus (SRL), on the development and progression of UVB-induced non-melanoma skin cancer. SKH-1 hairless mice were exposed to UVB alone for 15 weeks, and then were treated with CsA, SRL, or CsA+SRL for 9 weeks following cessation of UVB treatment. Compared with vehicle, CsA treatment resulted in enhanced tumor size and progression. In contrast, mice treated with SRL or CsA+SRL had decreased tumor multiplicity, size, and progression compared with vehicle-treated mice. CsA, but not SRL or combined treatment, increased dermal mast cell numbers and TGF-beta1 levels in the skin. These findings demonstrate that specific immunosuppressive agents differentially alter the cutaneous tumor microenvironment, which in turn may contribute to enhanced development of UVB-induced skin cancer in transplant recipients. Furthermore, these results suggest that CsA alone causes enhanced growth and progression of skin cancer, whereas co-administration of SRL with CsA causes the opposite effect. JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article please go to http://network.nature.com/group/jidclub

  7. Radiation therapy - skin care

    MedlinePlus

    ... numbness Skin sores Most of these symptoms will go away after your treatments have stopped. However, your skin may remain darker, drier, and more sensitive to the sun. When your hair grows back, it may be different than before.

  8. Squamous cell skin cancer

    MedlinePlus

    ... occur on skin that is regularly exposed to sunlight or other ultraviolet radiation. The earliest form of ... skin cancer is to reduce your exposure to sunlight . Always use sunscreen: Apply sunscreen with sun protection ...

  9. Components of skin

    MedlinePlus Videos and Cool Tools

    ... skin layers from the outside environment and contains cells that make keratin, a substance that waterproofs and strengthens the skin. The epidermis also has cells that contain melanin, the dark pigment that gives ...

  10. Skin, Hair, and Nails

    MedlinePlus

    ... thousands of cells and hundreds of sweat glands, oil glands, nerve endings, and blood vessels. Skin is ... empty into hair follicles and pores, produce the oil sebum that lubricates the skin and hair. Sebaceous ...

  11. Bleeding into the skin

    MedlinePlus

    Protect aging skin. Avoid trauma such as bumping or pulling on skin areas. For a cut or scrape, use direct pressure to stop the bleeding. If you have a drug reaction, ask your provider about stopping the drug. Otherwise, follow ...

  12. Bacterial Skin Infections

    MedlinePlus

    ... Diseases Take Big Slice Out of America's Health, Economy (News) Health Tip: Use Caution When Applying Hair Dye Additional ... Skin Diseases Take Big Slice Out of America's Health, Economy THURSDAY, March 2, 2017 (HealthDay News) -- Skin diseases ...

  13. Necrotizing Skin Infections

    MedlinePlus

    ... Diseases Take Big Slice Out of America's Health, Economy (News) Health Tip: Use Caution When Applying Hair Dye Additional ... Skin Diseases Take Big Slice Out of America's Health, Economy THURSDAY, March 2, 2017 (HealthDay News) -- Skin diseases ...

  14. Neuromodulators for Aging Skin

    MedlinePlus

    ... Stretch Marks Sun-damaged Skin Unwanted Hair Unwanted Tattoos Varicose Veins Vitiligo Wrinkles Treatments and Procedures Ambulatory ... Stretch Marks Sun-damaged Skin Unwanted Hair Unwanted Tattoos Varicose Veins Vitiligo Wrinkles Treatments and Procedures Ambulatory ...

  15. PPD skin test

    MedlinePlus

    ... is a method used to diagnose silent (latent) tuberculosis (TB) infection. PPD stands for purified protein derivative. ... skin test; Tuberculin skin test; Mantoux test Images Tuberculosis in the kidney Tuberculosis in the lung Positive ...

  16. Examine Your Skin

    MedlinePlus Videos and Cool Tools

    ... Store In Memory Melanoma Info Melanoma Facts Melanoma Prevention Sunscreen Suggestions Examine Your Skin Newly Diagnosed? Understanding ... video. UPDATED: November 23, 2016 Melanoma Facts Melanoma Prevention Sunscreen Suggestions Examine Your Skin Newly Diagnosed? Understanding ...

  17. Photoprotective Potential of Penta-O-Galloyl-β-DGlucose by Targeting NF-κB and MAPK Signaling in UVB Radiation-Induced Human Dermal Fibroblasts and Mouse Skin.

    PubMed

    Kim, Byung-Hak; Choi, Mi Sun; Lee, Hyun Gyu; Lee, Song-Hee; Noh, Kum Hee; Kwon, Sunho; Jeong, Ae Jin; Lee, Haeri; Yi, Eun Hee; Park, Jung Youl; Lee, Jintae; Joo, Eun Young; Ye, Sang-Kyu

    2015-11-01

    Exposure of the skin to ultraviolet radiation can cause skin damage with various pathological changes including inflammation. In the present study, we identified the skin-protective activity of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (pentagalloyl glucose, PGG) in ultraviolet B (UVB) radiation-induced human dermal fibroblasts and mouse skin. PGG exhibited antioxidant activity with regard to intracellular reactive oxygen species (ROS) generation as well as ROS and reactive nitrogen species (RNS) scavenging. Furthermore, PGG exhibited anti-inflammatory activity, inhibiting the activation of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling, resulting in inhibition of the expression of pro-inflammatory mediators. Topical application of PGG followed by chronic exposure to UVB radiation in the dorsal skin of hairless mice resulted in a significant decrease in the progression of inflammatory skin damages, leading to inhibited activation of NF-κB signaling and expression of pro-inflammatory mediators. The present study demonstrated that PGG protected from skin damage induced by UVB radiation, and thus, may be a potential candidate for the prevention of environmental stimuli-induced inflammatory skin damage.

  18. Photoprotective Potential of Penta-O-Galloyl-β-DGlucose by Targeting NF-κB and MAPK Signaling in UVB Radiation-Induced Human Dermal Fibroblasts and Mouse Skin

    PubMed Central

    Kim, Byung-Hak; Choi, Mi Sun; Lee, Hyun Gyu; Lee, Song-Hee; Noh, Kum Hee; Kwon, Sunho; Jeong, Ae Jin; Lee, Haeri; Yi, Eun Hee; Park, Jung Youl; Lee, Jintae; Joo, Eun Young; Ye, Sang-Kyu

    2015-01-01

    Exposure of the skin to ultraviolet radiation can cause skin damage with various pathological changes including inflammation. In the present study, we identified the skin-protective activity of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (pentagalloyl glucose, PGG) in ultraviolet B (UVB) radiation-induced human dermal fibroblasts and mouse skin. PGG exhibited antioxidant activity with regard to intracellular reactive oxygen species (ROS) generation as well as ROS and reactive nitrogen species (RNS) scavenging. Furthermore, PGG exhibited anti-inflammatory activity, inhibiting the activation of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling, resulting in inhibition of the expression of pro-inflammatory mediators. Topical application of PGG followed by chronic exposure to UVB radiation in the dorsal skin of hairless mice resulted in a significant decrease in the progression of inflammatory skin damages, leading to inhibited activation of NF-κB signaling and expression of pro-inflammatory mediators. The present study demonstrated that PGG protected from skin damage induced by UVB radiation, and thus, may be a potential candidate for the prevention of environmental stimuli-induced inflammatory skin damage. PMID:26537189

  19. Effects of chronic low-dose ultraviolet B radiation on DNA damage and repair in mouse skin.

    PubMed

    Mitchell, D L; Greinert, R; de Gruijl, F R; Guikers, K L; Breitbart, E W; Byrom, M; Gallmeier, M M; Lowery, M G; Volkmer, B

    1999-06-15

    Chronic exposure to sunlight causes skin cancer in humans, yet little is known about how habitual exposure to low doses of ultraviolet B radiation (UVB) affects DNA damage in the skin. We treated Skh-1 hairless mice with daily doses of suberythemal UVB for 40 days and analyzed the amount and distribution of DNA photodamage using RIAs and immunofluorescence micrography. We found that DNA damage accumulated in mouse skin as a result of chronic irradiation and that this damage persisted in the dermis and epidermis for several weeks after the chronic treatment was terminated. Although the persistent damage was evenly distributed throughout the dermis, it remained in the epidermis as a small number of heavily damaged cells at the dermal-epidermal boundary. Rates of DNA damage induction and repair were determined at different times over the course of chronic treatment in response to a higher challenge dose of UVB light. The amount of damage induced by the challenge dose increased in response to chronic exposure, and excision repair of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone dimers was significantly reduced. The sensitization of mouse epidermal DNA to photoproduct induction, the reduction in excision repair, and the accumulation of nonrepairable DNA damage in the dermis and epidermis suggest that chronic low-dose exposure to sunlight may significantly enhance the predisposition of mammalian skin to sunlight-induced carcinogenesis.

  20. Photodynamic therapy of murine non-melanoma skin carcinomas with diode laser after topical application of aluminum phthalocyanine chloride

    NASA Astrophysics Data System (ADS)

    Kyriazi, Maria; Alexandratou, Eleni; Yova, Dido; Rallis, Michail; Trebst, Tilmann

    2007-07-01

    The aim of this work is to study pharmacokinetics and photodynamic efficiency of aluminium phthalocyanine chloride (AlClPc) in dimethylsulfoxide/Tween 80/water solution, after topical application on hairless mice bearing non-melanoma skin carcinomas. The concentration of photosensitizer in normal skin and tumor biopsies 1-6 hours after application was assessed by fluorescence spectroscopy of chemical extractions. The concentration of photosensitizer was 40 times higher in tumor than in normal skin even 1 h after application. For photodynamic therapy (PDT) AlClPc was excited by a diode laser emitting at 670 nm, 1 h after application. Seven different combinations of therapeutic parameters were chosen. The efficiency was assessed as the percentage of complete tumor remission, the tumor growth retardation and the cosmetic outcomes. The highest complete remission 60% was achieved with the combination of 75 mW/cm2 with 150 J/cm2. No recurrence rate was observed in any treatment parameters group and the cosmetic outcome in all completely treated tumors was excellent. The results show that the effectiveness of PDT is highly dependent on fluence rate. In addition, they are promising for further investigation of this PDT scheme in preclinical studies mainly in non-melanoma skin carcinomas up to 7mm.

  1. Ultrasound skin imaging.

    PubMed

    Alfageme Roldán, F

    2014-12-01

    The interaction of high-frequency ultrasound waves with the skin provides the basis for noninvasive, fast, and accessible diagnostic imaging. This tool is increasingly used in skin cancer and inflammatory conditions as well as in cosmetic dermatology. This article reviews the basic principles of skin ultrasound and its applications in the different areas of dermatology.

  2. Skin self-exam

    MedlinePlus

    Skin cancer - self-exam; Melanoma - self-exam; Basal cell cancer - self-exam; Squamous cell - self-exam; Skin mole - self-exam ... Cancer Institute. What You Need To Know About Melanoma and Other Skin Cancers: How To Check Your ...

  3. Psychoneuroimmunology and the Skin.

    PubMed

    Honeyman, Juan F

    2016-08-23

    The nervous, immune, endocrine and integumentary systems are closely related and interact in a number of normal and pathological conditions. Nervous system mediators may bring about direct changes to the skin or may induce the release of immunological or hormonal mediators that cause pathological changes to the skin. This article reviews the psychological mechanisms involved in the development of skin diseases.

  4. Biology of Skin Color.

    ERIC Educational Resources Information Center

    Corcos, Alain

    1983-01-01

    Information from scientific journals on the biology of skin color is discussed. Major areas addressed include: (1) biology of melanin, melanocytes, and melanosomes; (2) melanosome and human diversity; (3) genetics of skin color; and (4) skin color, geography, and natural selection. (JN)

  5. Anyone Can Get Skin Cancer

    Cancer.gov

    No matter if your skin is light, dark, or somewhere in between, everyone is at risk for skin cancer. Learn what skin cancer looks like, how to find it early, and how to lower the chance of skin cancer.

  6. Sensitive skin: an overview.

    PubMed

    Inamadar, Arun C; Palit, Aparna

    2013-01-01

    Sensitive skin is less tolerant to frequent and prolonged use of cosmetics and toiletries. It is self-diagnosed and typically unaccompanied by any obvious physical signs of irritation. With the change in lifestyle and also with increased opportunity to use many new brands of cosmetics and toiletries, there has been an increase in females complaining of unique sensation in their facial skin. Sensitive skin presents as smarting, burning, stinging, itching, and/or tight sensation in their facial skin. The condition is found in more than 50% of women and 40% of men, creating a sizable demand for products designed to minimize skin sensitivity. Good numbers of invasive and non-invasive tests are designed to evaluate and predict the sensitive skin. Management includes guidelines for selecting suitable cosmetics and toiletries in sensitive skin individuals.

  7. Pursuing prosthetic electronic skin

    NASA Astrophysics Data System (ADS)

    Chortos, Alex; Liu, Jia; Bao, Zhenan

    2016-09-01

    Skin plays an important role in mediating our interactions with the world. Recreating the properties of skin using electronic devices could have profound implications for prosthetics and medicine. The pursuit of artificial skin has inspired innovations in materials to imitate skin's unique characteristics, including mechanical durability and stretchability, biodegradability, and the ability to measure a diversity of complex sensations over large areas. New materials and fabrication strategies are being developed to make mechanically compliant and multifunctional skin-like electronics, and improve brain/machine interfaces that enable transmission of the skin's signals into the body. This Review will cover materials and devices designed for mimicking the skin's ability to sense and generate biomimetic signals.

  8. [Skin diseases and obesity].

    PubMed

    Guerra-Segovia, Carolina; Ocampo-Candiani, Jorge

    2015-01-01

    Obesity is a public health problem worldwide. It predominates in industrialized countries; however, it is prevalent in all nations. It is defined as a condition of excess adipose tissue and is the result of changes in lifestyle, excessive consumption of energy-dense foods with poor nutritional value, physical inactivity and the reduction of open space where one can practice a sport. Although obesity is associated with multiple diseases, it is important to stress that the metabolic changes caused by it affect skin physiology and play a predisposing factor for the development of skin diseases. Very little has been studied on the impact of obesity on the skin. The purpose of this article is to review the most frequently skin diseases in obesity. Some skin pathologies in obesity are caused by changes in skin physiology, others are related to insulin resistance or constitute an exacerbating factor for dermatitis. This article covers the clinical features of obesity related skin disease and its management.

  9. Impact of Nrf2 on UVB-induced skin inflammation/photoprotection and photoprotective effect of sulforaphane.

    PubMed

    Saw, Constance L; Huang, Mou-Tuan; Liu, Yue; Khor, Tin Oo; Conney, Allan H; Kong, Ah-Ng

    2011-06-01

    Ultraviolet (UV) of sunlight is a complete carcinogen that can burn skin, enhance inflammation, and drive skin carcinogenesis. Previously, we have shown that sulforaphane (SFN) inhibited chemically induced skin carcinogenesis via nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and others have shown that broccoli sprout extracts containing high SFN protected against UV-induced skin carcinogenesis in SKH-1 hairless mice. A recent study showed that there was no difference between Nrf2 knockout (Nrf2 KO) and Nrf2 wild-type (WT) BALB/C mice after exposing to high dose of UVB. Since Nrf2 plays critical roles in the anti-oxidative stress/anti-inflammatory responses, it is relevant to assess the role of Nrf2 for photoprotection against UV. In this context, the role of Nrf2 in UVB-induced skin inflammation in Nrf2 WT and Nrf2 KO C57BL/6 mice was studied. A single dose of UVB (300 mJ/cm(2)) resulted in skin inflammation in both WT and Nrf2 KO (-/-) mice (KO mice) at 8 h and 8 d following UVB irradiation. In the WT mice inflammation returned to the basal level to a greater extent when compared to the KO mice. SFN treatment of Nrf2 WT but not Nrf2 KO mice restored the number of sunburn cells back to their basal level by 8 d after UVB irradiation. Additionally, UVB-induced short-term inflammatory biomarkers (interleukin-1β and interleukin-6) were increased in the KO mice and UVB-induced apoptotic cells in the KO mice were significantly higher as compared to that in the WT. Taken together, our results show that functional Nrf2 confers a protective effect against UVB-induced inflammation, sunburn reaction, and SFN-mediated photoprotective effects in the skin.

  10. The anti-inflammatory effect of alloferon on UVB-induced skin inflammation through the down-regulation of pro-inflammatory cytokines.

    PubMed

    Kim, Yejin; Lee, Seung Koo; Bae, Seyeon; Kim, Hyemin; Park, Yunseong; Chu, Nag Kyun; Kim, Stephanie G; Kim, Hang-Rae; Hwang, Young-Il; Kang, Jae Seung; Lee, Wang Jae

    2013-01-01

    UVB irradiation can induce biological changes in the skin, modulate immune responses and activate inflammatory reactions leading to skin damage. Alloferon, which is isolated from the blood of an experimentally infected insect, the blow fly Calliphora vicina, is known for its anti-viral and anti-tumor activities in mice model. However, the effect of alloferon against UVB irradiation and its specific mechanism are still unknown. In this study, we investigated the effect of alloferon on UVB-induced cutaneous inflammation in a human keratinocyte cell line, HaCaT. RPA and ELISA data showed that alloferon decreased the production of UVB-induced pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-6 and IL-18, both on the mRNA and protein level. Western blot analysis was done to determine if alloferon regulates the MAPK signaling pathway since the MAPK signaling pathway is activated by numerous inflammatory mediators and environmental stresses including UVB irradiation. Alloferon inhibited the activation of p38 mitogen-activated protein kinase (MAPK) induced by UVB irradiation. Furthermore, the topical application of alloferon on the UVB exposed skin of hairless mice showed that alloferon treatment significantly inhibited an increase in epithelial thickness in chronic UVB-irradiated mouse skin. These findings suggest that alloferon has significant anti-inflammatory effects not only on UVB-induced inflammation in the human keratinocyte cell line, HaCaT, but also on mouse skin.

  11. Time–course study of different innate immune mediators produced by UV-irradiated skin: comparative effects of short and daily versus a single harmful UV exposure

    PubMed Central

    Cela, Eliana M; Friedrich, Adrian; Paz, Mariela L; Vanzulli, Silvia I; Leoni, Juliana; González Maglio, Daniel H

    2015-01-01

    The modulatory effects of solar UV radiation on the immune system have been widely studied. As the skin is the main target of UV radiation, our purpose was to compare the impact on skin innate immunity of two contrasting ways to be exposed to sunlight. Hairless mice were UV irradiated with a single high UV dose simulating a harmful exposure, or with repetitive low UV doses simulating short occasional daily exposures. Skin samples were taken at different times after UV irradiation to evaluate skin histology, inflammatory cell recruitment, epidermal T-cell population and the mitochondrial function of epidermal cells. The transcriptional profiles of pro-inflammatory cytokines, chemokines, antimicrobial peptides and Toll-like receptors were evaluated by RT-PCR and ELISA in tissue homogenates. Finally, a lymphangiography was performed to assess modification in the lymphatic vessel system. A single high UV dose produces a deep inflammatory state characterized by the production of pro-inflammatory cytokines and chemokines that, in turn, induces the recruitment of neutrophils and macrophages into the irradiated area. On the other hand, repetitive low UV doses drive the skin to a photo-induced alert state in which there is no sign of inflammation, but the epithelium undergoes changes in thickness, the lymphatic circulation increases, and the transcription of antimicrobial peptides is induced. PMID:25438991

  12. (+)-2-(1-Hydroxyl-4-oxocyclohexyl) ethyl caffeate suppresses solar UV-induced skin carcinogenesis by targeting PI3-K, ERK1/2 and p38

    PubMed Central

    Lim, Do Young; Lee, Mee-Hyun; Shin, Seung Ho; Chen, Hanyoung; Ryu, Joohyun; Shan, Lei; Li, Honglin; Bode, Ann M.; Zhang, Wei-Dong; Dong, Zigang

    2014-01-01

    For decades, skin cancer incidence has increased, mainly due to oncogenic signaling pathways activated by solar ultraviolet (UV) irradiation (i.e., sun exposure). Solar UV induces multiple signaling pathways that are critical in the development of skin cancer, and therefore the development of compounds capable of targeting multiple molecules for chemoprevention of skin carcinogenesis is urgently needed. Herein, we examined the chemopreventive effects and the molecular mechanism of HOEC, [(+)-2-(1-hydroxyl-4-oxocyclohexyl) ethyl caffeate], isolated from Incarvillea mairei var. grandiflora (Wehrhahn) Grierson. HOEC strongly inhibited neoplastic transformation of JB6 C14l cells without toxicity. PI3-K, ERK1/2 and p38 kinase activities were suppressed by direct binding with HOEC in vitro. Our in silico docking data showed that HOEC binds at the ATP-binding site of each kinase. The inhibition of solar UV-induced PI3-K, ERK1/2 and p38 kinase activities resulted in suppression of their downstream signaling pathways and AP-1 and NF-κB transactivation in JB6 cells. Furthermore, topical application of HOEC reduced skin cancer incidence and tumor volume in SKH-1 hairless mice chronically exposed to solar UV. In summary, our results show that HOEC exerts inhibitory effects on multiple kinase targets and their downstream pathways activated by solar UV in vitro and in vivo. These findings suggest that HOEC is as a potent chemopreventive compound against skin carcinogenesis caused by solar UV exposure. PMID:24845061

  13. Dietary immunosuppressants do not enhance UV-induced skin carcinogenesis, and reveal discordance between p53-mutant early clones and carcinomas.

    PubMed

    Voskamp, Pieter; Bodmann, Carolien A; Koehl, Gudrun E; Rebel, Heggert G; Van Olderen, Marjolein G E; Gaumann, Andreas; El Ghalbzouri, Abdoel; Tensen, Cornelis P; Bavinck, Jan N Bouwes; Willemze, Rein; Geissler, Edward K; De Gruijl, Frank R

    2013-02-01

    Immunosuppressive drugs are thought to cause the dramatically increased risk of carcinomas in sun-exposed skin of organ transplant recipients. These drugs differ in local effects on skin. We investigated whether this local impact is predictive of skin cancer risk and may thus provide guidance on minimizing the risk. Immunosuppressants (azathioprine, cyclosporine, tacrolimus, mycophenolate mofetil, and rapamycin) were assessed on altering the UV induction of apoptosis in human skin models and of p53 mutant cell clones (putative tumor precursors) and ensuing skin carcinomas (with mutant p53) in the skin of hairless mice. Rapamycin was found to increase apoptosis (three-fold), whereas cyclosporine decreased apoptosis (three-fold). Correspondingly, a 1.5- to five-fold reduction (P = 0.07) or a two- to three-fold increase (P < 0.001) was found in cell clusters overexpressing mutant p53 in chronically UV-exposed skin of mice that had been fed rapamycin or cyclosporine, respectively. Deep sequencing showed, however, that the allelic frequency (∼5%) of the hotspot mutations in p53 (codons 270 and 275) remained unaffected. The majority of cells with mutated p53 seemed not to overexpress the mutated protein. Unexpectedly, none of the immunosuppressants admixed in high dosages to the diet accelerated tumor development, and cyclosporine even delayed tumor onset by approximately 15% (P < 0.01). Thus, in contrast to earlier findings, the frequency of p53-mutant cells was not predictive of the incidence of skin carcinoma. Moreover, the lack of any accelerative effect on tumor development suggests that immunosuppressive medication is not the sole cause of the dramatic increase in skin cancer risk in organ transplant recipients.

  14. Skin protection for hairdressers.

    PubMed

    Skudlik, Christoph; John, Swen Malte

    2007-01-01

    The application of protective creams in the hairdressing trade forms part of a complex concept for the prevention of occupational skin disorders. To date, no comparative controlled intervention studies have been carried out using different skin-protective creams. Previously published skin protection plans concerning barrier creams for the hairdressing trade are fairly general or rudimentary, reflecting our still limited knowledge on the subject. Bioengineering studies have even demonstrated a paradoxical effect of a certain skin-protective foam designed for hairdressers. Regarding other barrier creams, a certain protective effect could however be shown in studies concerning exposure to wetness and detergents. Pre-exposition skin protection seems to be of particular relevance. Thus, in principle, the regular application of adequate skin protection creams can be recommended in the hairdressing trade, although the protective effect should not be overvalued.

  15. Neuroendocrinology of the skin

    PubMed Central

    Zmijewski, Michal A

    2011-01-01

    The concept on the skin neuro-endocrine has been formulated ten years ago, and recent advances in the field further strengthened this role. Thus, skin forms a bidirectional platform for a signal exchange with other peripheral organs, endocrine and immune systems or brain to enable rapid and selective responses to the environment in order to maintain local and systemic homeostasis. In this context, it is not surprising that the function of the skin is tightly regulated by systemic neuro-endocrine system. Skin cells and skin appendages not only respond to neuropeptides, steroids and other regulatory signals, but also actively synthesis variety of hormones. The stress responses within the skin are tightly regulated by locally synthesized factors and their receptor expression. There is growing evidence for alternative splicing playing an important role in stress signaling. Deregulation of the skin neuro-endocrine signaling can lead or/and be a marker of variety of skin diseases. The major problem in this area relates to their detailed mechanisms of crosstalk between skin and brain and between the local and global endocrine as well as immune systems. PMID:21519402

  16. Skin care and incontinence

    MedlinePlus

    Incontinence - skin care; Incontinence - pressure sore; Incontinence - pressure ulcer ... redness, peeling, irritation, and yeast infections likely. Bedsores ( pressure sores ) may also develop if the person: Has ...

  17. Diffusion of (2-/sup 14/C)diazepam across isolated hairless mouse stratum corneum/epidermal tissues

    SciTech Connect

    Koch, R.L.; Palicharla, P.; Groves, M.J.

    1988-03-01

    The objective of this study was to develop a method of preparing mouse stratum corneum/epidermal (SCE) tissue without the dermis for use in drug diffusion studies. The diffusion of radiolabeled diazepam across this new preparation has been studied and the effect of the dermis on diffusion evaluated. Incubation of large pieces of mouse skin in a 20mM EDTA, 15 mM sodium phosphate buffer, pH 7.2, in normal saline for 3-4 h at 37 degrees C resulted in a tissue which easily separated at the epidermal-dermal junction. The resulting tissue contains stratum corneum and epidermis, which are the same layers used in studies with human skin in vitro. The EDTA treatment did not effect diffusion of (2-/sup 14/C)diazepam across whole mouse skin (SCE and dermis) used as controls. The rate of drug diffusion was greater across SCE than SCE and dermis, however, 0.48-1.12 micrograms/cm2/h versus 0.11-0.52 microgram/cm/h, respectively. The permeability coefficients for mouse SCE ranged from 1.92-4.48 X 10(-2) cm/h. The lag times and diffusion coefficients were 0.36-0.91 h and 0.1-0.6 X 10(-6) cm2/h, respectively. The presence of the dermis decreased the diffusion rate or flux of diazepam. The dermis appears to accumulate drug until it is saturated and then the drug diffuses into the receiving chamber.

  18. Effects of oral intake of kimchi-derived Lactobacillus plantarum K8 lysates on skin moisturizing.

    PubMed

    Kim, Hangeun; Kim, Hye Rim; Jeong, Bong Jun; Lee, Seung Su; Kim, Tae-Rahk; Jeong, Ji Hye; Lee, Miyeong; Lee, Sinai; Lee, Jong Suk; Chung, Dae Kyun

    2015-01-01

    Skin is the soft outer covering of vertebrates that provides protection from pathogenic infection, physical damage, or UV irradiation, and controls body temperature and water content. In this study, we examined the effects of oral intake of kimchi-derived Lactobacillus plantarum K8 lysates on skin moisturizing. In an in vitro study, we observed that the hyaluronic acid content increased in HaCaT cells treated with L. plantarum K8 lysates. Oral administration of L. plantarum K8 lysates effectively attenuated the horny layer formation and decreased epidermal thickening in DNCB-treated SKH-1 hairless mice skin. The damage to barrier function was reduced after 8 weeks of oral administration of L. plantarum K8 lysates as compared with that in the atopic dermatitis mice. For the test with volunteers, we manufactured experimental candy containing 2.1% L. plantarum K8 lysates, while control candy did not contain bacterial lysate. A significant increase in hydration in the experimental candy-administered group as compared with the control candy-administered group was observed on the face after 4 and 8 weeks, and on the forearm after 4 weeks. Decreases in horny layer thickness and TEWL value were observed on the face and forearm of the experimental group. Together, the in vitro cell line and in vivo mouse studies revealed that L. plantarum K8 lysates have a moisturizing effect. A clinical research study with healthy volunteers also showed an improvement in barrier repair and function when volunteers took L. plantarum K8 lysates-containing candy. Thus, our results suggest that L. plantarum K8 lysates may help to improve skin barrier function.

  19. Topical Formulation Containing Naringenin: Efficacy against Ultraviolet B Irradiation-Induced Skin Inflammation and Oxidative Stress in Mice.

    PubMed

    Martinez, Renata M; Pinho-Ribeiro, Felipe A; Steffen, Vinicius S; Silva, Thais C C; Caviglione, Carla V; Bottura, Carolina; Fonseca, Maria J V; Vicentini, Fabiana T M C; Vignoli, Josiane A; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rubia

    2016-01-01

    Naringenin (NGN) exhibits anti-inflammatory and antioxidant activities, but it remains undetermined its topical actions against ultraviolet B (UVB)-induced inflammation and oxidative stress in vivo. The purpose of this study was to evaluate the physicochemical and functional antioxidant stability of NGN containing formulations, and the effects of selected NGN containing formulation on UVB irradiation-induced skin inflammation and oxidative damage in hairless mice. NGN presented ferric reducing power, ability to scavenge 2,2'-azinobis (3-ethylbenzothiazoline- 6-sulfonic acid) (ABTS) and hydroxyl radical, and inhibited iron-independent and dependent lipid peroxidation. Among the three formulations containing NGN, only the F3 kept its physicochemical and functional stability over 180 days. Topical application of F3 in mice protected from UVB-induced skin damage by inhibiting edema and cytokine production (TNF-α, IL-1β, IL-6, and IL-10). Furthermore, F3 inhibited superoxide anion and lipid hydroperoxides production and maintained ferric reducing and ABTS scavenging abilities, catalase activity, and reduced glutathione levels. In addition, F3 maintained mRNA expression of cellular antioxidants glutathione peroxidase 1, glutathione reductase and transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), and induced mRNA expression of heme oxygenase-1. In conclusion, a formulation containing NGN may be a promising approach to protecting the skin from the deleterious effects of UVB irradiation.

  20. Fluoxetine Ameliorates Atopic Dermatitis-Like Skin Lesions in BALB/c Mice through Reducing Psychological Stress and Inflammatory Response

    PubMed Central

    Li, Yanxi; Chen, Long; Du, Yehong; Huang, Daochao; Han, Huili; Dong, Zhifang

    2016-01-01

    Atopic dermatitis (AD) is a common chronic inflammatory skin disorder, and patients with AD suffer from severe psychological stress, which markedly increases the prevalence rate of depression and anxiety disorders in later life. Fluoxetine, a selective serotonin reuptake inhibitor, has recently been reported to exert anti-inflammatory and immunosuppressive effects. However, it is unclear whether fluoxetine is effective in the treatment of AD through reducing psychological stress and inflammatory reaction. Here, we reported that a BALB/c mouse model of AD was induced by application of 2,4-dinitrochlorobenzene (DNCB) onto hairless dorsal skin. Chronic fluoxetine treatment (10 mg/kg per day, i.p.) significantly attenuated AD-like symptoms, as reflected by a dramatic decrease in scratching bouts, as well as a decrease in anxiety- and depressive-like behaviors. Furthermore, these behavioral changes were accompanied by a significant decrease in epidermal thickness, the number of mast cells in skin tissue, mRNA levels of interleukin-4 (IL-4) and IL-13 in the spleen, as well as serum immunoglobulin E (IgE) in the DNCB-treated mice by treatment with fluoxetine. Taken together, these results indicate that fluoxetine may suppress psychological stress and inflammatory response during AD development, and subsequently ameliorate AD symptoms, suggesting that fluoxetine may be a potential therapeutic agent against AD in clinic. PMID:27679577

  1. Mice drinking goji berry juice (Lycium barbarum) are protected from UV radiation-induced skin damage via antioxidant pathways.

    PubMed

    Reeve, Vivienne E; Allanson, Munif; Arun, Sondur Jayappa; Domanski, Diane; Painter, Nicole

    2010-04-01

    The goji berry, Lycium barbarum, has long been recognised in traditional Chinese medicine for various therapeutic properties based on its antioxidant and immune-modulating effects. This study describes the potential for orally consumed goji berry juice to alter the photodamage induced in the skin of mice by acute solar simulated UV (SSUV) irradiation. In Skh:hr-1 hairless mice, 5% goji berry juice significantly reduced the inflammatory oedema of the sunburn reaction. Dilutions of goji berry juice between 1% and 10% dose-dependently protected against SSUV-induced immunosuppression, and against suppression induced by the mediator, cis-urocanic acid, measured by the contact hypersensitivity reaction. The immune protection could not be ascribed to either the minor excipients in the goji juice, pear and apple juice, nor the vitamin C content, nor the preservative, and appeared to be a property of the goji berry itself. Antioxidant activity in the skin was demonstrated by the significant protection by 5% goji juice against lipid peroxidation induced by UVA radiation. Furthermore, two known inducible endogenous skin antioxidants, haem oxygenase-1 and metallothionein, were found to be involved in the photoimmune protection. The results suggest that consumption of this juice could provide additional photoprotection for susceptible humans.

  2. Topical Formulation Containing Naringenin: Efficacy against Ultraviolet B Irradiation-Induced Skin Inflammation and Oxidative Stress in Mice

    PubMed Central

    Martinez, Renata M.; Pinho-Ribeiro, Felipe A.; Steffen, Vinicius S.; Silva, Thais C. C.; Caviglione, Carla V.; Bottura, Carolina; Fonseca, Maria J. V.; Vicentini, Fabiana T. M. C.; Vignoli, Josiane A.; Baracat, Marcela M.; Georgetti, Sandra R.; Verri, Waldiceu A.; Casagrande, Rubia

    2016-01-01

    Naringenin (NGN) exhibits anti-inflammatory and antioxidant activities, but it remains undetermined its topical actions against ultraviolet B (UVB)-induced inflammation and oxidative stress in vivo. The purpose of this study was to evaluate the physicochemical and functional antioxidant stability of NGN containing formulations, and the effects of selected NGN containing formulation on UVB irradiation-induced skin inflammation and oxidative damage in hairless mice. NGN presented ferric reducing power, ability to scavenge 2,2′-azinobis (3-ethylbenzothiazoline- 6-sulfonic acid) (ABTS) and hydroxyl radical, and inhibited iron-independent and dependent lipid peroxidation. Among the three formulations containing NGN, only the F3 kept its physicochemical and functional stability over 180 days. Topical application of F3 in mice protected from UVB-induced skin damage by inhibiting edema and cytokine production (TNF-α, IL-1β, IL-6, and IL-10). Furthermore, F3 inhibited superoxide anion and lipid hydroperoxides production and maintained ferric reducing and ABTS scavenging abilities, catalase activity, and reduced glutathione levels. In addition, F3 maintained mRNA expression of cellular antioxidants glutathione peroxidase 1, glutathione reductase and transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), and induced mRNA expression of heme oxygenase-1. In conclusion, a formulation containing NGN may be a promising approach to protecting the skin from the deleterious effects of UVB irradiation. PMID:26741806

  3. Physiology of skin.

    PubMed

    Greaves, M W

    1976-07-01

    One of Montagna's greatest contributions to study of the biology of the skin has been his demolition of the artificial walls that traditionally separated the histologist from the physiologist. He has shown that only by relating function with structure can we shed light on the workings of the skin. He has stressed the fallacy of studying a single structural or functional unit in isolation from others. The skin represents an organization of many different functional units, and physiology of skin is the study of this organization. My purpose is to make a personal commentary on the achievements, failures, and prospects of understanding some aspects of the organization of the functional units. Twenty-five years ago, the importance of relating skin to internal organs and systems received much attention. We have long been aware that skin sometimes reacts to internal disease, but only recently has the impact of skin disorders on the circulatory, renal, and gastrointestinal systems been recognized. As a result, our patients are now less likely to suffer from neglect of the whole which follows narrow over-specialized attention to the part. Increased interest in endocrine effects on the skin has revealed that several important physiologic activities of the skin are either partly or wholly regulated by hormones secreted by endocrine glands. Nevertheless, some physiologic activities in skin seems to be independent, their regulation being carried out by local mediating hormones. Other activities involve both central and local regulation. The nature and roles of these two control mechanisms and their interrelation constitute by far the most promising physiologic research in skin.

  4. About Skin: Your Body's Largest Organ

    MedlinePlus

    ... your skin, hair, and nails Skin dictionary Camp Discovery Good Skin Knowledge lesson plans and activities Video library Find a ... your skin, hair, and nails Skin dictionary Camp Discovery Good Skin Knowledge lesson plans and activities Video library Find a ...

  5. Biothermomechanics of skin tissues

    NASA Astrophysics Data System (ADS)

    Xu, F.; Lu, T. J.; Seffen, K. A.

    Biothermomechanics of skin is highly interdisciplinary involving bioheat transfer, burn damage, biomechanics and neurophysiology. During heating, thermally induced mechanical stress arises due to the thermal denaturation of collagen, resulting in macroscale shrinkage. Thus, the strain, stress, temperature and thermal pain/damage are highly correlated; in other words, the problem is fully coupled. The aim of this study is to develop a computational approach to examine the heat transfer process and the heat-induced mechanical response, so that the differences among the clinically applied heating modalities can be quantified. Exact solutions for temperature, thermal damage and thermal stress for a single-layer skin model were first derived for different boundary conditions. For multilayer models, numerical simulations using the finite difference method (FDM) and finite element method (FEM) were used to analyze the temperature, burn damage and thermal stress distributions in the skin tissue. The results showed that the thermomechanical behavior of skin tissue is very complex: blood perfusion has little effect on thermal damage but large influence on skin temperature distribution, which, in turn, influences significantly the resulting thermal stress field; the stratum corneum layer, although very thin, has a large effect on the thermomechanical behavior of skin, suggesting that it should be properly accounted for in the modeling of skin thermal stresses; the stress caused by non-uniform temperature distribution in the skin may also contribute to the thermal pain sensation.

  6. Sun on Skin.

    ERIC Educational Resources Information Center

    Collins, Margaret

    1998-01-01

    Describes sessions in two schools that focused on recent work with 2,857 children in Europe researching the children's perceptions of sun on skin. Investigates children's ideas about skin on different parts of the body, which was most vulnerable to the sun, and different types and colors. (Author/CCM)

  7. Postmenopausal skin and estrogen.

    PubMed

    Archer, David F

    2012-10-01

    The aging global population continues to drive increasing demand for cosmaceuticals and cosmetic surgery among older men and women. Since the discovery in the 1990s that estrogen receptors are present in skin cells and decline in number from the onset of menopause in women, researchers have explored a number of ways in which estrogen can improve skin condition. Skin is estrogen responsive, and several studies now exist to support the antiaging properties of estrogen replacement therapies in postmenopausal women. Both systemic and topical estrogens appear to have positive effects on hormonal aging, increasing skin collagen content, thickness, elasticity and hydration. Estrogen therapies may also improve wound healing and reduce the incidence of wound complications. This review explores the potential for targeted estrogen replacement as a therapeutic option for long-term skin management in postmenopausal women.

  8. [Skin and sun exposure].

    PubMed

    Cannavò, Serafinella Patrizia; Borgia, Francesco; Trifirò, Caterina; Aragona, Emanuela

    2013-01-01

    Fisherman commonly experience a significant number of cutaneous problems, related to the exposure to environmental factors due to their working conditions. Among these factors, sun exposure is able to determine both acute and chronic skin damage, mostly linked to the effects of the ultraviolet (UV) radiation on epidermal and dermal structures. In particular, UV-A appears to play a major role in the deterioration of dermal structure leading to the photoaged appearance of the skin, while UV-B is mainly responsible for skin cancers. Peculiar clinical features of skin damage in fishermen include dryness, irregular pigmentation, wrinkling, stellate pseudoscars, elastosis, inelasticity, telangiectasia, comedones and sebaceous hyperplasia. Furtheremore, the high incidence of non-melanoma skin cancers, on sun-exposed areas, confirms the need for occupational health policies focusing on issues such as photoprotection.

  9. Therapeutic potential of a non-steroidal bifunctional anti-inflammatory and anti-cholinergic agent against skin injury induced by sulfur mustard.

    PubMed

    Chang, Yoke-Chen; Wang, James D; Hahn, Rita A; Gordon, Marion K; Joseph, Laurie B; Heck, Diane E; Heindel, Ned D; Young, Sherri C; Sinko, Patrick J; Casillas, Robert P; Laskin, Jeffrey D; Laskin, Debra L; Gerecke, Donald R

    2014-10-15

    Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 h post-SM exposure. After 96 h, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermal-epidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure.

  10. Therapeutic Potential of a Non-Steroidal Bifunctional Anti-Inflammatory and Anti-Cholinergic Agent against Skin Injury Induced by Sulfur Mustard

    PubMed Central

    Chang, Yoke-Chen; Wang, James D.; Hahn, Rita A.; Gordon, Marion K.; Joseph, Laurie B.; Heck, Diane E.; Heindel, Ned D.; Young, Sherri C.; Sinko, Patrick J.; Casillas, Robert P.; Laskin, Jeffrey D.; Laskin, Debra L.; Gerecke, Donald R.

    2014-01-01

    Sulfur mustard (bis(2-chloroethyl) sulfide, SM) is a highly reactive bifunctional alkylating agent inducing edema, inflammation, and the formation of fluid-filled blisters in the skin. Medical countermeasures against SM-induced cutaneous injury have yet to be established. In the present studies, we tested a novel, bifunctional anti-inflammatory prodrug (NDH 4338) designed to target cyclooxygenase 2 (COX2), an enzyme that generates inflammatory eicosanoids, and acetylcholinesterase, an enzyme mediating activation of cholinergic inflammatory pathways in a model of SM-induced skin injury. Adult SKH-1 hairless male mice were exposed to SM using a dorsal skin vapor cup model. NDH 4338 was applied topically to the skin 24, 48, and 72 hr post-SM exposure. After 96 hr, SM was found to induce skin injury characterized by edema, epidermal hyperplasia, loss of the differentiation marker, keratin 10 (K10), upregulation of the skin wound marker keratin 6 (K6), disruption of the basement membrane anchoring protein laminin 322, and increased expression of epidermal COX2. NDH 4338 post-treatment reduced SM-induced dermal edema and enhanced skin re-epithelialization. This was associated with a reduction in COX2 expression, increased K10 expression in the suprabasal epidermis, and reduced expression of K6. NDH 4338 also restored basement membrane integrity, as evidenced by continuous expression of laminin 332 at the dermalepidermal junction. Taken together, these data indicate that a bifunctional anti-inflammatory prodrug stimulates repair of SM induced skin injury and may be useful as a medical countermeasure. PMID:25127551

  11. Molecular cloning of the tomato Hairless gene implicates actin dynamics in trichome-mediated defense and mechanical properties of stem tissue

    PubMed Central

    Kang, Jin-Ho; Campos, Marcelo L.; Zemelis-Durfee, Starla; Al-Haddad, Jameel M.; Jones, A. Daniel; Telewski, Frank W.; Brandizzi, Federica; Howe, Gregg A.

    2016-01-01

    Trichomes are epidermal structures that provide a first line of defense against arthropod herbivores. The recessive hairless (hl) mutation in tomato (Solanum lycopersicum L.) causes severe distortion of trichomes on all aerial tissues, impairs the accumulation of sesquiterpene and polyphenolic compounds in glandular trichomes, and compromises resistance to the specialist herbivore Manduca sexta. Here, we demonstrate that the tomato Hl gene encodes a subunit (SRA1) of the highly conserved WAVE regulatory complex that controls nucleation of actin filaments in a wide range of eukaryotic cells. The tomato SRA1 gene spans a 42-kb region containing both Solyc11g013280 and Solyc11g013290. The hl mutation corresponds to a complex 3-kb deletion that removes the last exon of the gene. Expression of a wild-type SRA1 cDNA in the hl mutant background restored normal trichome development, accumulation of glandular trichome-derived metabolites, and resistance to insect herbivory. These findings establish a role for SRA1 in the development of tomato trichomes and also implicate the actin-cytoskeleton network in cytosolic control of specialized metabolism for plant defense. We also show that the brittleness of hl mutant stems is associated with altered mechanical and cell morphological properties of stem tissue, and demonstrate that this defect is directly linked to the mutation in SRA1. PMID:27481446

  12. A study of vascular response to thermal injury on hairless mice by fibre optic confocal imaging, laser doppler flowmetry and conventional histology.

    PubMed

    Vo, L T; Papworth, G D; Delaney, P M; Barkla, D H; King, R G

    1998-06-01

    Burn injury causes vascular thrombosis and occlusion by thermal damage to the vascular network in the dermis. In this study, fibre optic confocal imaging (FOCI) and laser doppler flowmetry were used to detect changes in vascular morphology and local dermal blood flux over 4 h, in three defined zones after a thermal burn (50 degrees C, 20 s duration, 3 mm in diameter) was induced on fully anaesthetised hairless mice. FITC-dextran (i.v.) was used to enable FOCI of vascular morphology including three-dimensional imaging of the burn site and its surrounding areas. Samples of the affected areas were collected for conventional histology, including Masson's trichrome. There was vascular damage in the zone of coagulation which showed no change during the 4 h period. The zone of stasis showed an initial reduction in blood flux and confocal imaging of the area indicated significant vessel leakage during the first 2 h which later improved. The zone of hyperaemia showed an initial increase in total blood flux and confocal imaging of the area showed initial blood vessel dilatation. This study demonstrates that FOCI is a useful non-invasive tool in the assessment of vascular changes in thermal burns in vivo, and compares the findings of FOCI with those from laser doppler flowmetry and histology.

  13. Extensive nonhomologous meiotic synapsis between normal chromosome axes of an rcp(3;6)(p14;q21) translocation in a hairless Mexican boar.

    PubMed

    Villagómez, D A F; Ayala-Valdovinos, M A; Galindo-García, J; Sánchez-Chipres, D R; Mora-Galindo, J; Taylor-Preciado, J J

    2008-01-01

    Due to its low fertility, expressed as small litter size, a Mexican hairless boar was subjected to cytogenetic investigation. Analysis of G-banded mitotic chromosomes revealed a reciprocal chromosome translocation, rcp(3;6) (p14;q21). Synaptonemal complex analysis showed a regular pairing behavior of the translocation chromosome axes, always resulting in a quadrivalent configuration. However, due to extensive nonhomologous pairing between the axes of nonderivative chromosomes 3 and 6, the quadrivalent mostly had an asymmetrical cross-shaped morphology. The nonhomologous pairing occurred not only at mid and late pachytene, but also at the earliest stage of pachytene. It seems that early pachytene heterosynapsis is a common phenomenon in the pairing behavior of pig reciprocal translocations. Therefore, heterosynapsis may reduce apoptosis of germ cells due to partial absence of homologous synapsis during the pairing phase of meiosis. The frequency of spermatocytes showing quadrivalent configurations with unpaired axial segments apparently did not affect germ cell progression in the boar, since fairly normal testicular histology was noticed.

  14. Molecular cloning of the tomato Hairless gene implicates actin dynamics in trichome-mediated defense and mechanical properties of stem tissue.

    PubMed

    Kang, Jin-Ho; Campos, Marcelo L; Zemelis-Durfee, Starla; Al-Haddad, Jameel M; Jones, A Daniel; Telewski, Frank W; Brandizzi, Federica; Howe, Gregg A

    2016-10-01

    Trichomes are epidermal structures that provide a first line of defense against arthropod herbivores. The recessive hairless (hl) mutation in tomato (Solanum lycopersicum L.) causes severe distortion of trichomes on all aerial tissues, impairs the accumulation of sesquiterpene and polyphenolic compounds in glandular trichomes, and compromises resistance to the specialist herbivore Manduca sexta Here, we demonstrate that the tomato Hl gene encodes a subunit (SRA1) of the highly conserved WAVE regulatory complex that controls nucleation of actin filaments in a wide range of eukaryotic cells. The tomato SRA1 gene spans a 42-kb region containing both Solyc11g013280 and Solyc11g013290 The hl mutation corresponds to a complex 3-kb deletion that removes the last exon of the gene. Expression of a wild-type SRA1 cDNA in the hl mutant background restored normal trichome development, accumulation of glandular trichome-derived metabolites, and resistance to insect herbivory. These findings establish a role for SRA1 in the development of tomato trichomes and also implicate the actin-cytoskeleton network in cytosolic control of specialized metabolism for plant defense. We also show that the brittleness of hl mutant stems is associated with altered mechanical and cell morphological properties of stem tissue, and demonstrate that this defect is directly linked to the mutation in SRA1.

  15. 6 Common Cancers - Skin Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Skin Cancer Past Issues / Spring 2007 Table of Contents For ... AP Photo/Herald-Mail, Kevin G. Gilbert Skin Cancer Skin cancer is the most common form of ...

  16. Urostomy - stoma and skin care

    MedlinePlus

    ... gov/ency/patientinstructions/000477.htm Urostomy - stoma and skin care To use the sharing features on this ... stoma if it is scraped. Caring for the Skin Around Your Stoma After surgery, the skin around ...

  17. Keratinocyte gene therapy for systemic diseases. Circulating interleukin 10 released from gene-transferred keratinocytes inhibits contact hypersensitivity at distant areas of the skin.

    PubMed Central

    Meng, X; Sawamura, D; Tamai, K; Hanada, K; Ishida, H; Hashimoto, I

    1998-01-01

    This study has examined the systemic effects of a circulating gene product, human interleukin 10 (IL-10), released from transduced keratinocytes. IL-10 is an anti-inflammatory cytokine which has an inhibitory effect on contact hypersensitivity (CHS). An expression vector (phIL-10) was constructed for human IL-10 and was injected into the dorsal skin of hairless rats. Local expression of IL-10 mRNA and protein was detected by reverse-transcriptase polymerase chain reaction and immunohistochemical staining, respectively. Enzyme-linked immunosorbent assay showed that the amount of IL-10 in the local keratinocytes and in the circulation increased with the dose of phIL-10 transferred. To determine whether circulating IL-10 could inhibit the effector phase of CHS at a distant area of the skin, various doses of phIL-10 were injected into the dorsal skin of sensitized rats before challenge on the ears. Our results showed that the degree of swelling of the ears of phIL-10- treated rats was significantly lower than that in the negative control animals. These results suggest that IL-10 released from transduced keratinocytes can enter the bloodstream and cause biological effects at distant areas of the skin. This study demonstrates that it may be possible to treat systemic disease using keratinocyte gene therapy. PMID:9502789

  18. Archaea on Human Skin

    PubMed Central

    Probst, Alexander J.; Auerbach, Anna K.; Moissl-Eichinger, Christine

    2013-01-01

    The recent era of exploring the human microbiome has provided valuable information on microbial inhabitants, beneficials and pathogens. Screening efforts based on DNA sequencing identified thousands of bacterial lineages associated with human skin but provided only incomplete and crude information on Archaea. Here, we report for the first time the quantification and visualization of Archaea from human skin. Based on 16 S rRNA gene copies Archaea comprised up to 4.2% of the prokaryotic skin microbiome. Most of the gene signatures analyzed belonged to the Thaumarchaeota, a group of Archaea we also found in hospitals and clean room facilities. The metabolic potential for ammonia oxidation of the skin-associated Archaea was supported by the successful detection of thaumarchaeal amoA genes in human skin samples. However, the activity and possible interaction with human epithelial cells of these associated Archaea remains an open question. Nevertheless, in this study we provide evidence that Archaea are part of the human skin microbiome and discuss their potential for ammonia turnover on human skin. PMID:23776475

  19. Skin and antioxidants.

    PubMed

    Poljsak, Borut; Dahmane, Raja; Godic, Aleksandar

    2013-04-01

    It is estimated that total sun exposure occurs non-intentionally in three quarters of our lifetimes. Our skin is exposed to majority of UV radiation during outdoor activities, e.g. walking, practicing sports, running, hiking, etc. and not when we are intentionally exposed to the sun on the beach. We rarely use sunscreens during those activities, or at least not as much and as regular as we should and are commonly prone to acute and chronic sun damage of the skin. The only protection of our skin is endogenous (synthesis of melanin and enzymatic antioxidants) and exogenous (antioxidants, which we consume from the food, like vitamins A, C, E, etc.). UV-induced photoaging of the skin becomes clinically evident with age, when endogenous antioxidative mechanisms and repair processes are not effective any more and actinic damage to the skin prevails. At this point it would be reasonable to ingest additional antioxidants and/or to apply them on the skin in topical preparations. We review endogenous and exogenous skin protection with antioxidants.

  20. Archaea on human skin.

    PubMed

    Probst, Alexander J; Auerbach, Anna K; Moissl-Eichinger, Christine

    2013-01-01

    The recent era of exploring the human microbiome has provided valuable information on microbial inhabitants, beneficials and pathogens. Screening efforts based on DNA sequencing identified thousands of bacterial lineages associated with human skin but provided only incomplete and crude information on Archaea. Here, we report for the first time the quantification and visualization of Archaea from human skin. Based on 16 S rRNA gene copies Archaea comprised up to 4.2% of the prokaryotic skin microbiome. Most of the gene signatures analyzed belonged to the Thaumarchaeota, a group of Archaea we also found in hospitals and clean room facilities. The metabolic potential for ammonia oxidation of the skin-associated Archaea was supported by the successful detection of thaumarchaeal amoA genes in human skin samples. However, the activity and possible interaction with human epithelial cells of these associated Archaea remains an open question. Nevertheless, in this study we provide evidence that Archaea are part of the human skin microbiome and discuss their potential for ammonia turnover on human skin.

  1. Sensitive skin: an overview.

    PubMed

    Berardesca, E; Farage, M; Maibach, H

    2013-02-01

    Sensitive skin is a condition of subjective cutaneous hyper-reactivity to environmental factors. Subjects experiencing this condition report exaggerated reactions when their skin is in contact with cosmetics, soaps and sun screens, and they often report worsening after exposure to dry and cold climate. Although no sign of irritation is commonly detected, itching, burning, stinging and a tight sensation are constantly present. Generally substances that are not commonly considered irritants are involved in this abnormal response.Sensitive skin and subjective irritation are widespread but still far from being completely defined and understood. A correlation between sensitive skin and constitutional anomalies and/or other triggering factors such as occupational skin diseases or chronic exposure to irritants has been hypothesized. Recent findings suggest that higher sensitivity can be due to different mechanisms. Hyper-reactors may have a thinner stratum corneum with a reduced corneocyte area causing a higher transcutaneous penetration of water-soluble chemicals. Alterations in vanilloid receptors and changes in neuronal transmission have been described. Monitoring skin parameters such as barrier function, proclivity to irritation, corneocyte size and sensorial transmission can also be useful to identify regional differences in skin sensitivity.

  2. The Ontogeny of Skin

    PubMed Central

    Visscher, Marty; Narendran, Vivek

    2014-01-01

    Significance: During gestation, fetal skin progresses from a single layer derived from ectoderm to a complex, multi-layer tissue with the stratum corneum (SC) as the outermost layer. Innate immunity is a conferred complex process involving a balance of pro- and anti-inflammatory cytokines, structural proteins, and specific antigen-presenting cells. The SC is a part of the innate immune system as an impermeable physical barrier containing anti-microbial lipids and host defense proteins. Postnatally, the epidermis continually replenishes itself, provides a protective barrier, and repairs injuries. Recent Advances: Vernix caseosa protects the fetus during gestation and facilitates development of the SC in the aqueous uterine environment. The anti-infective, hydrating, acidification, and wound-healing properties post birth provide insights for the development of strategies that facilitate SC maturation and repair in the premature infant. Critical Issues: Reduction of infant mortality is a global health priority. Premature infants have an incompetent skin barrier putting them at risk for irritant exposure, skin compromise and life-threatening infections. Effective interventions to accelerate skin barrier maturation are compelling. Future Directions: Investigations to determine the ontogeny of barrier maturation, that is, SC structure, composition, cohesiveness, permeability, susceptibility to injury, and microflora, as a function of gestational age are essential. Clinicians need to know when the premature skin barrier becomes fully competent and comparable to healthy newborn skin. This will guide the development of innovative strategies for optimizing skin barrier development. PMID:24761361

  3. Environment and the skin

    PubMed Central

    Suskind, Raymond R.

    1977-01-01

    The skin is an important interface between man and his environment; it is an important portal of entry for hazardous agents and a vulnerable target tissue as well. It is a uniquely accessible model system for detecting hazards and for studying mechanisms of a wide variety of biologic funcitons. Environmental causes of skin reactions comprise a vast array of physical, chemical and biological agents. To appreciate the role of the skin as an interface with man's environment, it is necessary to understand the multiple adaptive mechanisms, and the defenses of the skin against the environmental stresses. The skin is endowed with a versatile group of defenses against penetration, fluid loss from the body, thermal stress, solar radiation, physical trauma and microbial agents. Patterns of adverse response range in quality and intensity from uncomplicated itching to metastatic neoplasia. Environmental problems comprise a large segment of disabling skin disease. Although critical epidemiologic data is limited, cutaneous illnesses comprise a significant segment of occupational disease. This represents a significant loss in productivity and a major cause of disability. The most serious research needs include the development of surveillance systems for identifying skin hazards and determining frequency of environmental skin disease; the development of new models for studying cutaneous penetration; the elucidation of the mechanisms of nonallergic inflammatory reactions (primary irritation) and of the accommodation phenomenon; the development of more sensitive models for predicting adverse responses to marginal irritants; the utilization of modern skills of immunobiology and immunochemistry to elucidate mechanisms of allergic responses; the launching of epidemiologic studies to determine the long term effects of PCBs and associated compounds such as dioxins; and the expansion of research in the mechanisms of skin cancer in relation to susceptibility, genetic and metabolic

  4. Thermal Skin fabrication technology

    NASA Technical Reports Server (NTRS)

    Milam, T. B.

    1972-01-01

    Advanced fabrication techniques applicable to Thermal Skin structures were investigated, including: (1) chemical machining; (2) braze bonding; (3) diffusion bonding; and (4) electron beam welding. Materials investigated were nickel and nickel alloys. Sample Thermal Skin panels were manufactured using the advanced fabrication techniques studied and were structurally tested. Results of the program included: (1) development of improved chemical machining processes for nickel and several nickel alloys; (2) identification of design geometry limits; (3) identification of diffusion bonding requirements; (4) development of a unique diffusion bonding tool; (5) identification of electron beam welding limits; and (6) identification of structural properties of Thermal Skin material.

  5. Eicosanoids in skin inflammation.

    PubMed

    Nicolaou, Anna

    2013-01-01

    Eicosanoids play an integral part in homeostatic mechanisms related to skin health and structural integrity. They also mediate inflammatory events developed in response to environmental factors, such as exposure to ultraviolet radiation, and inflammatory and allergic disorders, including psoriasis and atopic dermatitis. This review article discusses biochemical aspects related to cutaneous eicosanoid metabolism, the contribution of these potent autacoids to skin inflammation and related conditions, and considers the importance of nutritional supplementation with bioactives such as omega-3 and omega-6 polyunsaturated fatty acids and plant-derived antioxidants as means of addressing skin health issues.

  6. Skin, Hair, and Nails

    MedlinePlus

    ... and water, helps regulate body temperature through perspiration (sweating), and protects from the sun's damaging ultraviolet rays. ... skin contains thousands of cells and hundreds of sweat glands, oil glands, nerve endings, and blood vessels. ...

  7. Skin Cancer Screening

    MedlinePlus

    ... the body's largest organ . It protects against heat, sunlight, injury, and infection . Skin also helps control body ... cancer risk factors include: Being exposed to natural sunlight or artificial sunlight (such as from tanning beds) ...

  8. Skin Cancer Prevention

    MedlinePlus

    ... the body’s largest organ . It protects against heat, sunlight, injury, and infection . Skin also helps control body ... it is most common in areas exposed to sunlight, such as the face, neck, hands, and arms. ...

  9. Healthy Skin Matters

    MedlinePlus

    ... don’t offer a safe alternative to natural sunlight. Exposure to ultraviolet (UV ) (uhl-truh-VYE-uh- ... the exposure comes from tanning beds or natural sunlight. This damage increases the risk of skin cancer ...

  10. Aging changes in skin

    MedlinePlus

    ... sun exposure with areas that are protected from sunlight. Natural pigments seem to provide some protection against ... Exposures to industrial and household chemicals Indoor heating Sunlight can cause: Loss of elasticity (elastosis) Noncancerous skin ...

  11. Acral peeling skin syndrome.

    PubMed

    Hashimoto, K; Hamzavi, I; Tanaka, K; Shwayder, T

    2000-12-01

    Peeling skin syndrome is a rare autosomal recessive disease characterized by widespread painless peeling of the skin in superficial sheets. We describe a 34-year-old man with a lifelong history of spontaneous asymptomatic peeling skin limited to the acral surfaces. This patient probably represents a localized variant of peeling skin syndrome, which has previously been described as a generalized condition. Light and electron microscopic studies of biopsy specimens taken before and after immersion in water were performed. It was concluded that this patient has abnormal keratohyalin granules and inadequate aggregation of keratin filaments that caused the separation of the epidermis in the stratum corneum through the clear zone. Alternatively, unknown keratin species expressed in the clear zone may also cause the abnormality. (J Am Acad Dermatol 2000;43:1112-9.).

  12. Skin lesion KOH exam

    MedlinePlus

    ... is present. The fungus may be related to ringworm , athlete's foot , jock itch , or another fungal infection. ... foot Candida infection of the skin Jock itch Ringworm Ringworm of the body Review Date 4/14/ ...

  13. Allergy testing - skin

    MedlinePlus

    ... may order allergy skin tests if you have: Hay fever ( allergic rhinitis ) and asthma symptoms that are not ... team. Related MedlinePlus Health Topics Allergy Food Allergy Hay Fever Browse the Encyclopedia A.D.A.M., Inc. ...

  14. An elastic second skin

    NASA Astrophysics Data System (ADS)

    Yu, Betty; Kang, Soo-Young; Akthakul, Ariya; Ramadurai, Nithin; Pilkenton, Morgan; Patel, Alpesh; Nashat, Amir; Anderson, Daniel G.; Sakamoto, Fernanda H.; Gilchrest, Barbara A.; Anderson, R. Rox; Langer, Robert

    2016-08-01

    We report the synthesis and application of an elastic, wearable crosslinked polymer layer (XPL) that mimics the properties of normal, youthful skin. XPL is made of a tunable polysiloxane-based material that can be engineered with specific elasticity, contractility, adhesion, tensile strength and occlusivity. XPL can be topically applied, rapidly curing at the skin interface without the need for heat- or light-mediated activation. In a pilot human study, we examined the performance of a prototype XPL that has a tensile modulus matching normal skin responses at low strain (<40%), and that withstands elongations exceeding 250%, elastically recoiling with minimal strain-energy loss on repeated deformation. The application of XPL to the herniated lower eyelid fat pads of 12 subjects resulted in an average 2-grade decrease in herniation appearance in a 5-point severity scale. The XPL platform may offer advanced solutions to compromised skin barrier function, pharmaceutical delivery and wound dressings.

  15. Skin lesion removal

    MedlinePlus

    ... removal; Basal cell cancer - removal; Actinic keratosis - removal; Wart - removal; Squamous cell - removal; Mole - removal; Nevus - removal; ... can remove: Benign or pre-malignant skin lesions Warts Moles Sunspots Hair Small blood vessels in the ...

  16. Allergy Skin Tests

    MedlinePlus

    ... allergic rhinitis) Allergic asthma Dermatitis (eczema) Food allergies Penicillin allergy Bee venom allergy Latex allergy Skin tests are ... may recommend this test to check for an allergy to insect venom or penicillin. Patch test Patch testing is generally done to ...

  17. Skin tumors on squirrels

    USGS Publications Warehouse

    Herman, C.M.; Reilly, J.R.

    1955-01-01

    Skin tumors having the gross appearance of previously reported fibromas are reported on gray squirrels from N. Y., Md., Va., N. C., and W. Va. and from a fox squirrel from W. Va. and a porcupine from Pa.

  18. Genetics and skin aging

    PubMed Central

    Makrantonaki, Evgenia; Bekou, Vassiliki; Zouboulis, Christos C.

    2012-01-01

    Skin aging is a complex process and underlies multiple influences with the probable involvement of heritable and various environmental factors. Several theories have been conducted regarding the pathomechanisms of aged skin, however fundamental mechanisms still remain poorly understood. This article addresses the influence of genetics on skin aging and in particular deals with the differences observed in ethnic populations and between both genders. Recent studies indicate that male and female aged skin differs as far as the type, the consistency and the sensitivity to external factors is concerned. The same has been also documented between elderly people of different origin. Consequently, the aging process taking place in both genders and in diverse ethnic groups should be examined separately and products specialized to each population should be developed in order to satisfy the special needs. PMID:23467395

  19. Skin or nail culture

    MedlinePlus

    Mucosal culture; Culture - skin; Culture - mucosal; Nail culture; Culture - fingernail; Fingernail culture ... There, it is placed in a special dish (culture). It is then watched to see if bacteria, ...

  20. Skin Reactions to Cold

    PubMed Central

    Talpash, Orest

    1976-01-01

    Although skin reactions to cold are seen surprisingly infrequently in Canada, it is important to manage them correctly when they do occur. Frostbite, cold urticarias, Raynaud's disease and phenomenon, and several miscellaneous changes are discussed. PMID:21308019

  1. Chromophores in human skin

    NASA Astrophysics Data System (ADS)

    Young, Antony R.

    1997-05-01

    Human skin, especially the epidermis, contains several major solar ultraviolet-radiation- (UVR-) absorbing endogenous chromophores including DNA, urocanic acid, amino acids, melanins and their precursors and metabolites. The lack of solubility of melanins prevents their absorption spectra being defined by routine techniques. Indirect spectroscopic methods show that their spectral properties depend on the stimulus for melanogenesis. The photochemical consequences of UVR absorption by some epidermal chromophores are relatively well understood whereas we lack a detailed understanding of the consequent photobiological and clinical responses. Skin action spectroscopy is not a reliable way of relating a photobiological outcome to a specific chromophore but is important for UVR hazard assessment. Exogenous chromophores may be administered to the skin in combination with UVR exposure for therapeutic benefit, or as sunscreens for the prevention of sunburn and possibly skin cancer.

  2. Skin Diseases: Cross-section of human skin

    MedlinePlus

    Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Cross-section of human skin Past Issues / Fall 2008 Table of Contents For ... Logical Images, Inc. I n the areas of skin health and skin diseases, the NIH's National Institute ...

  3. Common Skin Cancers

    PubMed Central

    Ho, Vincent C.

    1992-01-01

    Melanoma, basal cell carcinoma, and squamous cell carcinoma are the three most common forms of skin cancer. The incidence of skin cancer is increasing at an alarming rate. Early detection is the key to successful management. In this article, the salient clinical features and diagnostic clues for these tumors and their precursor lesions are presented. Current management guidelines are also discussed. ImagesFigure 1Figures 2-3Figures 4-6Figures 7-9 PMID:21221380

  4. Nicotinamide and the skin.

    PubMed

    Chen, Andrew C; Damian, Diona L

    2014-08-01

    Nicotinamide, an amide form of vitamin B3, boosts cellular energy and regulates poly-ADP-ribose-polymerase 1, an enzyme with important roles in DNA repair and the expression of inflammatory cytokines. Nicotinamide shows promise for the treatment of a wide range of dermatological conditions, including autoimmune blistering disorders, acne, rosacea, ageing skin and atopic dermatitis. In particular, recent studies have also shown it to be a potential agent for reducing actinic keratoses and preventing skin cancers.

  5. Leishmania Skin Test

    DTIC Science & Technology

    2010-03-01

    Ninhydrin ), SDS-PAGE and non-viability testing . See Table 3 below: Table 3: Drug Substance Specifications Test Method Specification SDS-PAGE...AD_________________ Award Number: DAMD17-00-C-0030 TITLE: Leishmania Skin Test PRINCIPAL INVESTIGATOR: Nielsen, H.S., Jr...TYPE FINAL, PHASE II ADDENDUM 3. DATES COVERED (From - To) 1 APR 2009 - 28 FEB 2010 4. TITLE AND SUBTITLE Leishmania Skin Test 5a

  6. Rheumatologic Skin Disease.

    PubMed

    Kalus, Andrea

    2015-11-01

    In common rheumatologic diseases skin findings are an important diagnostic clue for astute clinicians. Skin manifestations can help identify systemic disease or may require therapy uniquely targeted at the cutaneous problem. This article discusses 3 common rheumatologic conditions seen in adults by dermatologists: cutaneous lupus, dermatomyositis, and morphea. The focus is on the cutaneous findings and clinical presentation. Some approaches to treatment are explored. Clues to help identify systemic disease are also highlighted.

  7. Fractional derivatives in the transport of drugs across biological materials and human skin

    NASA Astrophysics Data System (ADS)

    Caputo, Michele; Cametti, Cesare

    2016-11-01

    The diffusion of drugs across a composite structure such as a biological membrane is a rather complex phenomenon, because of its inhomogeneous nature, yielding a diffusion rate and a drug solubility strongly dependent on the local position across the membrane itself. These problems are particularly strengthened in composite structures of a considerable thickness like, for example, the human skin, where the high heterogeneity provokes the transport through different simultaneous pathways. In this note, we propose a generalization of the diffusion model based on Fick's 2nd equation by substituting a diffusion constant by means of the memory formalism approach (diffusion with memory). In particular, we employ two different definitions of the fractional derivative, i.e., the usual Caputo fractional derivative and a new definition recently proposed by Caputo and Fabrizio. The model predictions have been compared to experimental results concerning the permeation of two different compounds through human skin in vivo, such as piroxicam, an anti-inflammatory drug, and 4-cyanophenol, a test chemical model compound. Moreover, we have also considered water penetration across human stratum corneum and the diffusion of an antiviral agent employed as model drugs across the skin of male hairless rats. In all cases, a satisfactory good agreement based on the diffusion with memory has been found. However, the model based on the new definition of fractional derivative gives a better description of the experimental data, on the basis of the residuals analysis. The use of the new definition widens the applicability of the fractional derivative to diffusion processes in highly heterogeneous systems.

  8. Ultraflexible organic photonic skin

    PubMed Central

    Yokota, Tomoyuki; Zalar, Peter; Kaltenbrunner, Martin; Jinno, Hiroaki; Matsuhisa, Naoji; Kitanosako, Hiroki; Tachibana, Yutaro; Yukita, Wakako; Koizumi, Mari; Someya, Takao

    2016-01-01

    Thin-film electronics intimately laminated onto the skin imperceptibly equip the human body with electronic components for health-monitoring and information technologies. When electronic devices are worn, the mechanical flexibility and/or stretchability of thin-film devices helps to minimize the stress and discomfort associated with wear because of their conformability and softness. For industrial applications, it is important to fabricate wearable devices using processing methods that maximize throughput and minimize cost. We demonstrate ultraflexible and conformable three-color, highly efficient polymer light-emitting diodes (PLEDs) and organic photodetectors (OPDs) to realize optoelectronic skins (oe-skins) that introduce multiple electronic functionalities such as sensing and displays on the surface of human skin. The total thickness of the devices, including the substrate and encapsulation layer, is only 3 μm, which is one order of magnitude thinner than the epidermal layer of human skin. By integrating green and red PLEDs with OPDs, we fabricate an ultraflexible reflective pulse oximeter. The device unobtrusively measures the oxygen concentration of blood when laminated on a finger. On-skin seven-segment digital displays and color indicators can visualize data directly on the body. PMID:27152354

  9. Coriander Leaf Extract Exerts Antioxidant Activity and Protects Against UVB-Induced Photoaging of Skin by Regulation of Procollagen Type I and MMP-1 Expression

    PubMed Central

    Hwang, Eunson; Lee, Do-Gyeong; Park, Sin Hee; Oh, Myung Sook

    2014-01-01

    Abstract Ultraviolet (UV) radiation causes photodamage to the skin, which, in turn, leads to depletion of the dermal extracellular matrix and chronic alterations in skin structure. Skin wrinkles are associated with collagen synthesis and matrix metalloproteinase-1 (MMP-1) activity. Coriandrum sativum L. (coriander leaf, cilantro; CS) has been used as a herbal medicine for the treatment of diabetes, hyperlipidemia, liver disease, and cancer. In this study, we examined whether CS ethanol extract (CSE) has protective effects against UVB-induced skin photoaging in normal human dermal fibroblasts (NHDF) in vitro and in the skin of hairless mice in vivo. The main component of CSE, linolenic acid, was determined by gas chromatography-mass spectroscopy. We measured the cellular levels of procollagen type I and MMP-1 using ELISA in NHDF cells after UVB irradiation. NHDF cells that were treated with CSE after UVB irradiation exhibited higher procollagen type I production and lower levels of MMP-1 than untreated cells. We found that the activity of transcription factor activator protein-1 (AP-1) was also inhibited by CSE treatment. We measured the epidermal thickness, dermal collagen fiber density, and procollagen type I and MMP-1 levels in photo-aged mouse skin in vivo using histological staining and western blot analysis. Our results showed that CSE-treated mice had thinner epidermal layers and denser dermal collagen fibers than untreated mice. On a molecular level, it was further confirmed that CSE-treated mice had lower MMP-1 levels and higher procollagen type I levels than untreated mice. Our results support the potential of C. sativum L. to prevent skin photoaging. PMID:25019675

  10. Coriander leaf extract exerts antioxidant activity and protects against UVB-induced photoaging of skin by regulation of procollagen type I and MMP-1 expression.

    PubMed

    Hwang, Eunson; Lee, Do-Gyeong; Park, Sin Hee; Oh, Myung Sook; Kim, Sun Yeou

    2014-09-01

    Ultraviolet (UV) radiation causes photodamage to the skin, which, in turn, leads to depletion of the dermal extracellular matrix and chronic alterations in skin structure. Skin wrinkles are associated with collagen synthesis and matrix metalloproteinase-1 (MMP-1) activity. Coriandrum sativum L. (coriander leaf, cilantro; CS) has been used as a herbal medicine for the treatment of diabetes, hyperlipidemia, liver disease, and cancer. In this study, we examined whether CS ethanol extract (CSE) has protective effects against UVB-induced skin photoaging in normal human dermal fibroblasts (NHDF) in vitro and in the skin of hairless mice in vivo. The main component of CSE, linolenic acid, was determined by gas chromatography-mass spectroscopy. We measured the cellular levels of procollagen type I and MMP-1 using ELISA in NHDF cells after UVB irradiation. NHDF cells that were treated with CSE after UVB irradiation exhibited higher procollagen type I production and lower levels of MMP-1 than untreated cells. We found that the activity of transcription factor activator protein-1 (AP-1) was also inhibited by CSE treatment. We measured the epidermal thickness, dermal collagen fiber density, and procollagen type I and MMP-1 levels in photo-aged mouse skin in vivo using histological staining and western blot analysis. Our results showed that CSE-treated mice had thinner epidermal layers and denser dermal collagen fibers than untreated mice. On a molecular level, it was further confirmed that CSE-treated mice had lower MMP-1 levels and higher procollagen type I levels than untreated mice. Our results support the potential of C. sativum L. to prevent skin photoaging.

  11. A novel papillomavirus isolated from proliferative skin lesions of a wild American beaver (Castor canadensis).

    PubMed

    Rogovskyy, Artem S; Baszler, Timothy V; Bradway, Daniel S; Bruning, Darren L; Davitt, Christine M; Evermann, James F; Burk, Robert D; Chen, Zigui; Mansfield, Kristin G; Haldorson, Gary J

    2012-07-01

    Cutaneous papillomatosis was diagnosed in an adult American beaver (Castor canadensis). Gross lesions included numerous exophytic, roughly circular, lightly pigmented lesions on hairless areas of fore and hind feet and the nose. The most significant histopathologic findings were multifocal papilliform hyperplasia of the superficial stratified squamous epithelium, with multifocal koilocytes, and multiple cells with large, darkly basophilic intranuclear inclusion bodies. A virus with properties consistent with papillomavirus (PV) was recovered by virus isolation of skin lesions, utilizing rabbit and feline kidney cell lines. The presence of the virus was confirmed by PV-specific polymerase chain reaction. The partial sequences of E1 and L1 genes did not closely match those of any PVs in GenBank, suggesting that this might be a new type of PV. Partial E1 and L1 nucleotide sequences of the beaver papillomavirus (hereafter, ARbeaver-PV1) were used to create a phylogenetic tree employing the complete E1 and L1 open reading frame nucleotide sequences of 68 PVs. The phylogenetic tree placed the ARbeaver-PV1 in a clade that included the Mupapillomavirus (HPV1 and HPV63) and Kappapapillomavirus (OcPV1 and SfPV1) genera. The present article confirms the papillomaviral etiology of cutaneous exophytic lesions in the beaver.

  12. Spiritual and religious aspects of skin and skin disorders

    PubMed Central

    Shenefelt, Philip D; Shenefelt, Debrah A

    2014-01-01

    Skin and skin disorders have had spiritual aspects since ancient times. Skin, hair, and nails are visible to self and others, and touchable by self and others. The skin is a major sensory organ. Skin also expresses emotions detectable by others through pallor, coldness, “goose bumps”, redness, warmth, or sweating. Spiritual and religious significances of skin are revealed through how much of the skin has been and continues to be covered with what types of coverings, scalp and beard hair cutting, shaving and styling, skin, nail, and hair coloring and decorating, tattooing, and intentional scarring of skin. Persons with visible skin disorders have often been stigmatized or even treated as outcasts. Shamans and other spiritual and religious healers have brought about healing of skin disorders through spiritual means. Spiritual and religious interactions with various skin disorders such as psoriasis, leprosy, and vitiligo are discussed. Religious aspects of skin and skin diseases are evaluated for several major religions, with a special focus on Judaism, both conventional and kabbalistic. PMID:25120377

  13. [Autoimmune bullous skin disorders].

    PubMed

    Hertl, Michael; Niedermeier, Andrea; Borradori, Luca

    2010-09-01

    Autoimmune bullous skin disorders are rare, potentially fatal disorders of skin and mucous membranes which are associated with IgG or IgA autoantibodies against distinct adhesion molecules of the epidermis and dermal epidermal basement membrane zone, respectively. These autoantibodies lead to a loss of skin adhesion which shows up clinically as the formation of blisters or erosions. In pemphigus, loss of adhesion occurs within the epidermis while in the pemphigoids, linear IgA dermatosis, epidermolysis bullosa acquisita and dermatitis herpetiformis, loss of adhesion takes place within or underneath the basement membrane zone. The autoantigens of these disorders are largely identified and characterized. Making the diagnosis of autoimmune bullous skin diseases is based on histology and direct immunofluorescence of perilesional skin and the serological detection of autoantibodides by indirect immunofluorescence and recombinant autoantigens. Therapeutically, systemic treatment with glucocorticoids is combined with immunosuppressive adjuvants which allow for the fast reduction of systemic steroids. A prospective trial in pemphigus showed that adjuvant treatment with azathioprine, mycophenolate mofetil and cyclophosphamide, respectively, led to a significant reduction of the cummulative dose of systemic steroids until complete clinical remission was achieved. In bullous pemphigoid, topical treatment with clobetasol led to complete clinical remissions without major side effects seen when glucocorticoids were applied systemically. Therapeutic depletion of B cells by rituximab as a second line therapy has significantly improved the overall prognosis of pemphigus. Comparable controlled therapeutic trials have not yet been performed in dermatitis herpetiformis and epidermolysis bullosa acquisita.

  14. Skin friction balance

    NASA Technical Reports Server (NTRS)

    Ping, Tcheng (Inventor); Supplee, Frank H., Jr. (Inventor)

    1989-01-01

    A skin friction balance uses a parallel linkage mechanism to avoid inaccuracies in skin friction measurement attributable to off-center normal forces. The parallel linkage mechanism includes a stationary plate mounted in a cage, and an upper and lower movable plate which are linked to each other and to the stationary plate throught three vertical links. Flexure pivots are provided for pivotally connecting the links and the plates. A sensing element connected to the upper plate moves in response to skin friction, and the lower plate moves in the opposite direction of the upper plate. A force motor maintains a null position of the sensing element by exerting a restoring force in response to a signal generated by a linear variable differential transformer (LVDT).

  15. Update on skin allergy.

    PubMed

    Schlapbach, C; Simon, D

    2014-12-01

    Skin diseases with an allergic background such as atopic dermatitis, allergic contact dermatitis, and urticaria are very common. Moreover, diseases arising from a dysfunction of immune cells and/or their products often manifest with skin symptoms. This review aims to summarize recently published articles in order to highlight novel research findings, clinical trial results, and current guidelines on disease management. In recent years, an immense progress has been made in understanding the link between skin barrier dysfunction and allergic sensitization initiating the atopic march. In consequence, new strategies for treatment and prevention have been developed. Novel pathogenic insights, for example, into urticaria, angioedema, mastocytosis, led to the development of new therapeutic approaches and their implementation in daily patient care. By understanding distinct pathomechanisms, for example, the role of IL-1, novel entities such as autoinflammatory diseases have been described. Considerable effort has been made to improve and harmonize patient management as documented in several guidelines and position papers.

  16. Sprayed skin turbine component

    DOEpatents

    Allen, David B

    2013-06-04

    Fabricating a turbine component (50) by casting a core structure (30), forming an array of pits (24) in an outer surface (32) of the core structure, depositing a transient liquid phase (TLP) material (40) on the outer surface of the core structure, the TLP containing a melting-point depressant, depositing a skin (42) on the outer surface of the core structure over the TLP material, and heating the assembly, thus forming both a diffusion bond and a mechanical interlock between the skin and the core structure. The heating diffuses the melting-point depressant away from the interface. Subsurface cooling channels (35) may be formed by forming grooves (34) in the outer surface of the core structure, filling the grooves with a fugitive filler (36), depositing and bonding the skin (42), then removing the fugitive material.

  17. Environment and the skin

    SciTech Connect

    Suskind, R.R. )

    1990-03-01

    The skin is an important organ of defense adaptation and a portal of entry for xenobiotics. It is vulnerable to physical, chemical, and biologic agents and capable of expressing responses to these agents in a variety of pathologic patterns. These patterns are characterized by morphologic and functional features which are elicited by careful examination and test procedures. Cutaneous cancer may result from exposure to nonionizing as well as ionizing radiation, to specific identifiable chemical hazards, and may be enhanced by trauma. Cutaneous hazards of chemical sources are largely found in the workplace and among consumer products, including drugs and toilet goods. Environmental skin diseases and injuries are preventable. Prior to use assessment for safety and for possible risks from exposure to an agent, product, or process is of primary importance in the prevention and control of environmental skin disease and injury.

  18. Noninvasive Optical Imaging of UV-Induced Squamous Cell Carcinoma in Murine Skin: Studies of Early Tumor Development and Vitamin D Enhancement of Protoporphyrin IX Production

    PubMed Central

    Rollakanti, Kishore R.; Anand, Sanjay; Davis, Scott C.; Pogue, Brian W.; Maytin, Edward V.

    2015-01-01

    Better noninvasive techniques are needed to monitor protoporphyrin IX (PpIX) levels before and during photodynamic therapy (PDT) of squamous cell carcinoma (SCC) of the skin. Our aim was to evaluate: (1) multispectral fluorescent imaging of ultraviolet light (UV)-induced cancer and precancer in a mouse model of SCC; (2) multispectral imaging and probe-based fluorescence detection as a tool to study Vitamin D (VD) effects on aminolevulinic acid (ALA)-induced PpIX synthesis. Dorsal skin of hairless mice was imaged weekly during a 24-week UV carcinogenesis protocol. Hot spots of PpIX fluorescence were detectable by multispectral imaging beginning at 14 weeks of UV exposure. Many hot spots disappeared after cessation of UV at week 20, but others persisted or became visible after week 20, and corresponded to tumors that eventually became visible by eye. In SCC-bearing mice pretreated with topical VD before ALA application, our optical techniques confirmed that VD preconditioning induces a tumor-selective increase in PpIX levels. Fluorescence-based optical imaging of PpIX is a promising tool for detecting early SCC lesions of the skin. Pretreatment with VD can increase the ability to detect early tumors, providing a potential new way to improve efficacy of ALA-PDT. PMID:26223149

  19. [The skin and alopecia].

    PubMed

    Ishihara, Kazuyuki

    2003-06-01

    Adverse skin reactions to anti-tumor agents, can be classified either as general symptoms or as local symptoms. The former type of symptom can manifest as intoxication dermatosis; however, while its occurrence is rare, the symptom that requires the closest attention is toxic epidermal necrolysis, the outcome of which is death in most patients. The latter type of symptom includes extravasation of anti-tumor agents and alopecia. Treatment of extravasation induced skin disorders includes prompt and repeated local injections of steroids, while treatment of alopecia includes scalp cooling and external therapies.

  20. The relationship between skin maturation and electrical skin impedance.

    PubMed

    Emery, M M; Hebert, A A; Aguirre Vila-Coro, A; Prager, T C

    1991-09-01

    When performing electrophysiological testing, high electrical impedance values are sometimes found in neonates. Since excessive impedance can invalidate test results, a study was conducted to delineate the relationship between skin maturation and electrical skin impedance. This study investigated the skin impedance in 72 infants ranging from 196 to 640 days of age from conception. Regression analyses demonstrated a significant relationship between impedance and age, with the highest impedance centered around full-term gestation with values falling precipitously at time points on either side. Clinically, impedance values fall to normal levels at approximately four months following full-term gestation. Skin impedance values are low in premature infants, but rapidly increase as the age approaches that of full-term neonates. Low impedance values in premature infants are attributed to greater skin hydration which results from immature skin conditions such as 1) thinner epidermal layers particularly at the transitional and cornified layers; 2) more blood flow to the skin; and 3) higher percentage of water composition. These factors facilitate the diffusion of water vapor through the skin. As the physical barrier to skin water loss matures with gestational age, the skin impedance reaches a maximum value at full term neonatal age. After this peak, a statistically significant inverse relationship exists between electrical skin impedance and age in the first year of life. This drop in skin impedance is attributed to an increase in skin hydration as a result of the greater functional maturity of eccrine sweat glands.

  1. Study of surfactant-skin interactions by skin impedance measurements.

    PubMed

    Lu, Guojin; Moore, David J

    2012-02-01

    The stratum corneum (SC) plays a very critical physiological role as skin barrier in regulating water loss through the skin and protects the body from a wide range of physical and chemical exogenous insults. Surfactant-containing formulations can induce skin damage and irritation owing to surfactant absorption and penetration. It is generally accepted that reduction in skin barrier properties occurs only after surfactants have penetrated/permeated into the skin barrier. To mitigate the harshness of surfactant-based cleansing products, penetration/permeation of surfactants should be reduced. Skin impedance measurements have been taken in vitro on porcine skin using vertical Franz diffusion cells to investigate the impact of surfactants, temperature and pH on skin barrier integrity. These skin impedance results demonstrate excellent correlation with other published methods for assessing skin damage and irritation from different surfactant chemistry, concentration, pH, time of exposure and temperature. This study demonstrates that skin impedance can be utilized as a routine approach to screen surfactant-containing formulations for their propensity to compromise the skin barrier and hence likely lead to skin irritation.

  2. Protection against 12-O-tetradecanoylphorbol-13-acetate-caused inflammation in SENCAR mouse ear skin by polyphenolic fraction isolated from green tea.

    PubMed

    Katiyar, S K; Agarwal, R; Ekker, S; Wood, G S; Mukhtar, H

    1993-03-01

    Earlier studies conducted in our laboratory have shown that a polyphenolic fraction isolated from green tea (GTP) possesses anti-skin tumor initiating and anti-skin tumor promoting activity in the two-stage skin tumorigenesis protocol in SENCAR mouse. We have also shown that topical application of GTP inhibits tumor promoter-caused induction of epidermal ornithine decarboxylase activity in SENCAR mice in a dose-dependent manner, and that its oral feeding in drinking water to SKH-1 hairless mice enhances antioxidant and phase II enzyme activity in liver, lung, small bowel and skin. In this study, we show that single or multiple applications of GTP on SENCAR mouse ear prior to or after the application of 12-O-tetradecanoylphorbol-13-acetate (TPA) afford significant protection (P < 0.05) against TPA-induced edema. Pre-application of GTP also afforded significant protection against TPA-induced hyperplasia in the ear skin. The percentage protection by GTP both in terms of epidermal thickness and vertical cell layers was 75 and 90% respectively (P < 0.005). In further studies, we assessed the protective effect of GTP against TPA-caused infiltration of neutrophils in the ear skin of SENCAR mouse, by determining a naturally occurring constituent of neutrophils, myeloperoxidase, as a quantitative marker of tissue neutrophil content. Prior application of GTP resulted in significant protection against TPA-caused infiltration of neutrophils (P < 0.005). These results suggest that GTP possesses potential as a cancer chemopreventive agent against stage I tumor promotion.

  3. About Skin-to-Skin Care (Kangaroo Care)

    MedlinePlus

    ... Size Email Print Share About Skin-to-Skin Care Page Content Article Body You may be able ... care, also called kangaroo care. What is Kangaroo Care? Kangaroo care was developed in South America as ...

  4. Silibinin prevents ultraviolet B radiation-induced epidermal damages in JB6 cells and mouse skin in a p53-GADD45α-dependent manner.

    PubMed

    Roy, Srirupa; Deep, Gagan; Agarwal, Chapla; Agarwal, Rajesh

    2012-03-01

    Better preventive strategies are required to reduce ultraviolet (UV)-caused photodamage, the primary etiological factor for non-melanoma skin cancer (NMSC). Accordingly, here we examined the preventive efficacy of silibinin against UVB-induced photodamage using mouse epidermal JB6 cells and SKH1 hairless mouse epidermis. In JB6 cells, silibinin pretreatment protected against apoptosis and accelerated the repair of cyclobutane pyrimidine dimers (CPD) induced by moderate dose of UVB (50 mJ/cm(2)), which we are at risk of daily exposure. Silibinin also reversed UVB-induced S phase arrest, reducing both active DNA synthesizing and inactive S phase populations. In mechanistic studies, UVB-irradiated cells showed a transient upregulation of both phosphorylated (Ser-15 and Ser-392) and total p53, whereas silibinin pretreatment led to a more sustained upregulation and stronger nuclear localization of p53. Silibinin also caused a marked upregulation of GADD45α, a downstream target of p53, implicated in DNA repair and cell cycle regulation. Importantly, under p53 and GADD45α knockdown conditions, cells were more susceptible to UVB-induced apoptosis without any significant S phase arrest, and protective effects of silibinin were compromised. Similar to the in vitro results, topical application of silibinin prior to or immediately after UVB irradiation resulted in sustained increase in p53 and GADD45α levels and accelerated CPD removal in the epidermis of SKH1 hairless mice. Together, our results show for the first time that p53-mediated GADD45α upregulation is the key mechanism by which silibinin protects against UVB-induced photodamage and provides a strong rationale to investigate silibinin in reducing the risk and/or preventing early onset of NMSC.

  5. Chemokines and skin diseases.

    PubMed

    Sugaya, Makoto

    2015-04-01

    Chemokines are small molecules that induce chemotaxis and activation of certain subsets of leukocytes. The expression patterns of chemokines and chemokine receptors are specific to certain organs and cells. Therefore, chemokines are important to elucidate the mechanism of organ-specific human diseases. CCL17 expressed by Langerhans cells, blood endothelial cells, and fibroblasts plays a key role in attracting Th2 cells and tumor cells of adult T-cell leukemia/lymphoma and mycosis fungoides/Sézary syndrome into the skin, developing various Th2-type inflammatory skin diseases as well as cutaneous lymphoma. CCL11 and CCL26 expressed by skin-resident cells, such as fibroblasts, blood endothelial cells, and keratinocytes, induce infiltration of CCR3-expressing cells such as Th2 cells and eosinophils. CCL11 may also serve as an autocrine as well as a paracrine in anaplastic large cell lymphoma. CX3CL1 expressed on blood endothelial cells leads to infiltration of CX3CR1(+) immune cells, such as mast cells, neutrophils, and macrophages, playing important roles in wound healing, tumor immunity, and vasculitis. Biologics targeting chemokines and their receptors are promising strategies for various skin diseases that are resistant to the current therapy.

  6. [Main parasitic skin disorders].

    PubMed

    Bernigaud, C; Monsel, G; Delaunay, P; Do-Pham, G; Foulet, F; Botterel, F; Chosidow, O

    2017-01-01

    Cutaneous parasitic skin diseases are frequent in human pathology. There are few reliable epidemiological data on the prevalence and/or incidence of such diseases. Skin parasites are cosmopolitan but their global distribution is heterogenous; prevalence is especially high in subtropical and tropical countries. They are mainly due to arthropods (insects and mites). Many species of parasites are involved, explaining the diversity of their clinical signs. The most common are caused by ectoparasites such as scabies or pediculosis (head lice, body lice and pubic lice). Clinical signs may be related to the penetration of the parasite under the skin, its development, the inoculation of venom or allergic symptoms. Diagnosis can be easy when clinical signs are pathognomonic (e.g. burrows in the interdigital web spaces in scabies) or sometimes more difficult. Some epidemiological characteristics (diurnal or nocturnal bite, seasonality) and specific clinical presentation (single or multiple bites, linear or grouped lesions) can be a great diagnostic help. Modern non-invasive tools (dermoscopy or confocal microscopy) will play an important role in the future but the eye and experience of the specialist (dermatologist, parasitologist, infectious disease specialist or entomologist) remains for the time the best way to guide or establish a diagnosis. For most skin parasites, therapeutic proposals are rarely based on studies of high level of evidence or randomized trials but more on expert recommendations or personal experience.

  7. CSD skin test

    MedlinePlus

    ... features on this page, please enable JavaScript. The cat scratch disease (CSD) skin test was once used to help ... Slater LN, Welch DF, Koehler JE. Bartonella, including cat-scratch disease. In: Bennett JE, Dolin R, Blaser MJ, eds. ...

  8. Skin lesion of blastomycosis

    MedlinePlus

    ... A.D.A.M. Editorial team. Related MedlinePlus Health Topics Fungal Infections Skin Infections Browse the Encyclopedia A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare ... for online health information and services. Learn more about A.D. ...

  9. Skin graft - slideshow

    MedlinePlus

    ... anatomy URL of this page: //medlineplus.gov/ency/presentations/100100.htm Skin graft - series—Normal anatomy To use the sharing features on this page, please enable JavaScript. Go to slide 1 out of 4 Go to slide 2 ...

  10. The Role of the Skin Barrier in Occupational Skin Diseases.

    PubMed

    Kasemsarn, Pranee; Bosco, Joanna; Nixon, Rosemary L

    2016-01-01

    Occupational skin diseases (OSDs) are the second most common occupational diseases worldwide. Occupational contact dermatitis (OCD) is the most frequent OSD, and comprises irritant contact dermatitis (ICD), allergic contact dermatitis (ACD), contact urticaria and protein contact dermatitis. There are many endogenous and exogenous factors which affect the development of OCD, including age, sex, ethnicity, atopic skin diathesis, certain occupations and environmental factors. One of the most important contributing causes is skin barrier dysfunction. The skin provides a first-line defense from environmental assaults and incorporates physical, chemical and biological protection. Skin barrier disturbance plays a crucial role in various skin diseases such as atopic dermatitis (AD), ichthyosis, ICD and ACD. Genetic factors, such as filaggrin gene (FLG) mutations, and external factors, such as skin irritants interfering with stratum corneum structure and composition, may lead to abnormalities in skin barrier function and increased vulnerability to skin diseases. FLG encodes the cornified envelope protein, filaggrin, which is involved in skin barrier function. FLG mutation is associated with the development of OCD. High-risk occupations for OCD include health care workers, hairdressers and construction workers. There are often multiple contributing causes to OCD, as workers are exposed to both irritants and allergens. AD is also associated with skin barrier disruption and plays an important role in OCD. ICD often precedes and facilitates the development of ACD, with impairment of the skin barrier contributing to the concurrence of ICD and ACD in many workers with OCD.

  11. Breast skin and nipple changes

    MedlinePlus

    ... treatment. SCALY, FLAKING, ITCHY SKIN This is usually eczema or a bacterial or fungal infection. See your ... Atopic dermatitis, eczema, and noninfectious immunodeficiency disorders. In: James WD, Berger TG, Elston DM, eds. Andrews' Diseases of the Skin: Clinical ...

  12. Radiation Therapy for Skin Cancer

    MedlinePlus

    ... than in African-Americans. TYPES OF SKIN CANCER Basal cell carcinoma: This is the most common form of skin ... epidermis ). Radiation therapy is very effective for treating basal cell cancers that have not spread elsewhere. Other common treatments ...

  13. Staining of skin with dihydroxyacetone.

    PubMed

    WITTGENSTEIN, E; BERRY, H K

    1960-09-30

    The reaction of skin with dihydroxyacetone to produce a brown "artificial tan" appears to proceed through combination with free amino groups in skin proteins, and particularly by combination of dihydroxyacetone with the free guanido group in arginine.

  14. Enhanced skin regeneration by nanoegg formulation of all-trans retinoic acid.

    PubMed

    Yamaguchi, Y; Nakamura, N; Nagasawa, T; Kitagawa, A; Matsumoto, K; Soma, Y; Matsuda, T; Mizoguchi, M; Igarashi, R

    2006-02-01

    All-trans retinoic acid (atRA) which could smooth wrinkles and produce less pigmented skin after a few months of treatment has been studied in research into topical treatments for a potent inhibitor of new melanin production. However, the clinical responses of commercial atRA cream predominantly comprise severe inflammation. We report a novel nanotechnology "nanoegg" system giving improved effects of atRA self-assembly which were coated by CaCO3. Dorsal areas of hairless mouse and porcine skin were employed for administration of nanoegg ointment and commercial products. The mRNA for heparin-binding epidermal growth factor-like growth factor (HB-EGF) from tissues was measured by a real-time PCR method. All tissues were stained for detection of hyaluronate and the thickness of the epidermis. A clinical trial in humans was carried out at St. Marianna University in Japan. As a result, the irritation and inflammation associated with atRA molecules were substantially reduced. The physicochemical instability of atRA was also dramatically improved. Furthermore, nanoegg enhanced marked expression of mRNA for HB-EGF from keratinocytes, which is known as one of the markers of keratinocyte turnover. Also, production of hyaluronate was surprisingly in the intercellular spaces of the basal and spinous cell layers 2 days after treatment. Even at the low concentration of atRA in the nanoegg system, the proliferation and differentiation of keratinocyte was somewhat enhanced. A nanoegg may thus not only prevent adverse effects, but also markedly enhance the main effect.

  15. Nicotinamide for skin cancer chemoprevention.

    PubMed

    Damian, Diona L

    2017-03-20

    Nicotinamide (vitamin B3 ) has a range of photoprotective effects in vitro and in vivo; it enhances DNA repair, reduces UV radiation-induced suppression of skin immune responses, modulates inflammatory cytokine production and skin barrier function and restores cellular energy levels after UV exposure. Pharmacological doses of nicotinamide have been shown to reduce actinic keratoses and nonmelanoma skin cancer incidence in high-risk individuals, making this a nontoxic and accessible option for skin cancer chemoprevention in this population.

  16. Brain-Skin Connection: Stress, Inflammation and Skin Aging

    PubMed Central

    Chen, Ying; Lyga, John

    2014-01-01

    The intricate relationship between stress and skin conditions has been documented since ancient times. Recent clinical observations also link psychological stress to the onset or aggravation of multiple skin diseases. However, the exact underlying mechanisms have only been studied and partially revealed in the past 20 years or so. In this review, the authors will discuss the recent discoveries in the field of “Brain-Skin Connection”, summarizing findings from the overlapping fields of psychology, endocrinology, skin neurobiology, skin inflammation, immunology, and pharmacology. PMID:24853682

  17. Skin Pedagogies and Abject Bodies

    ERIC Educational Resources Information Center

    Kenway, Jane; Bullen, Elizabeth

    2011-01-01

    How does the beauty industry "narrate the skin"? What does it teach women from different cultural groups about the female body? How does skin function as a site where female subjection and abjection are produced and reproduced? In this paper we examine the skin industry pointing to its extreme commodification of the female body and to the…

  18. Skin cancer: Etiology and management.

    PubMed

    Qadir, Muhammad Imran

    2016-05-01

    Nowadays, occurrence of skin cancer is very common in humans. It is reported that the most common cause of the skin cancer is excessive exposure to sunlight as it contains harmful radiations; the ultra violet rays. Different management strategies are used for different types of skin cancers, which are chemotherapy, radiation therapy.

  19. Polyamines and nonmelanoma skin cancer

    SciTech Connect

    Gilmour, Susan K.

    2007-11-01

    Elevated levels of polyamines have long been associated with skin tumorigenesis. Tightly regulated metabolism of polyamines is critical for cell survival and normal skin homeostasis, and these controls are dysregulated in skin tumorigenesis. A key enzyme in polyamine biosynthesis, ornithine decarboxylase (ODC) is upregulated in skin tumors compared to normal skin. Use of transgenic mouse models has demonstrated that polyamines play an essential role in the early promotional phase of skin tumorigenesis. The formation of skin tumors in these transgenic mice is dependent upon polyamine biosynthesis, especially putrescine, since treatment with inhibitors of ODC activity blocks the formation of skin tumors and causes the rapid regression of existing tumors. Although the mechanism by which polyamines promote skin tumorigenesis are not well understood, elevated levels of polyamines have been shown to stimulate epidermal proliferation, alter keratinocyte differentiation status, increase neovascularization, and increase synthesis of extracellular matrix proteins in a manner similar to that seen in wound healing. It is becoming increasingly apparent that elevated polyamine levels activate not only epidermal cells but also underlying stromal cells in the skin to promote the development and progression of skin tumors. The inhibition of polyamine biosynthesis has potential to be an effective chemoprevention strategy for nonmelanoma skin cancer.

  20. Ablative skin resurfacing.

    PubMed

    Agrawal, Nidhi; Smith, Greg; Heffelfinger, Ryan

    2014-02-01

    Ablative laser resurfacing has evolved as a safe and effective treatment for skin rejuvenation. Although traditional lasers were associated with significant thermal damage and lengthy recovery, advances in laser technology have improved safety profiles and reduced social downtime. CO2 lasers remain the gold standard of treatment, and fractional ablative devices capable of achieving remarkable clinical improvement with fewer side effects and shorter recovery times have made it a more practical option for patients. Although ablative resurfacing has become safer, careful patient selection and choice of suitable laser parameters are essential to minimize complications and optimize outcomes. This article describes the current modalities used in ablative laser skin resurfacing and examines their efficacy, indications, and possible side effects.

  1. Adenolipoma of the skin.

    PubMed

    Del Agua, C; Felipo, F

    2004-10-15

    Adenolipoma of the skin is an unusual variant of lipoma recently described by Hitchcock et al. and characterized by the presence of normal eccrine sweat glands within a lipoma. We report a case and review the literature. A 45-year-old woman presented with a slow-growing, painless nodule on the thigh, clinically considered to be lipoma. Microscopically it comprised an adipose-tissue proliferation with a single eccrine secretory coil and associated duct in the periphery and in the center of the nodule. This benign lesion has been termed adenolipoma because of the presence of adipose tissue and eccrine glands. It probably represents only a histological curiosity in which the eccrine glands are entrapped by the adipose proliferation. Adenolipoma of the skin is a distinct lesion that can occur in the dermis or subcutaneous tissue.

  2. Skin contamination dosimeter

    DOEpatents

    Hamby, David M.; Farsoni, Abdollah T.; Cazalas, Edward

    2011-06-21

    A technique and device provides absolute skin dosimetry in real time at multiple tissue depths simultaneously. The device uses a phoswich detector which has multiple scintillators embedded at different depths within a non-scintillating material. A digital pulse processor connected to the phoswich detector measures a differential distribution (dN/dH) of count rate N as function of pulse height H for signals from each of the multiple scintillators. A digital processor computes in real time from the differential count-rate distribution for each of multiple scintillators an estimate of an ionizing radiation dose delivered to each of multiple depths of skin tissue corresponding to the multiple scintillators embedded at multiple corresponding depths within the non-scintillating material.

  3. Skin barrier in rosacea.

    PubMed

    Addor, Flavia Alvim Sant'Anna

    2016-01-01

    Recent studies about the cutaneous barrier demonstrated consistent evidence that the stratum corneum is a metabolically active structure and also has adaptive functions, may play a regulatory role in the inflammatory response with activation of keratinocytes, angiogenesis and fibroplasia, whose intensity depends primarily on the intensity the stimulus. There are few studies investigating the abnormalities of the skin barrier in rosacea, but the existing data already show that there are changes resulting from inflammation, which can generate a vicious circle caused a prolongation of flare-ups and worsening of symptoms. This article aims to gather the most relevant literature data about the characteristics and effects of the state of the skin barrier in rosacea.

  4. Skin barrier in rosacea*

    PubMed Central

    Addor, Flavia Alvim Sant'Anna

    2016-01-01

    Recent studies about the cutaneous barrier demonstrated consistent evidence that the stratum corneum is a metabolically active structure and also has adaptive functions, may play a regulatory role in the inflammatory response with activation of keratinocytes, angiogenesis and fibroplasia, whose intensity depends primarily on the intensity the stimulus. There are few studies investigating the abnormalities of the skin barrier in rosacea, but the existing data already show that there are changes resulting from inflammation, which can generate a vicious circle caused a prolongation of flare-ups and worsening of symptoms. This article aims to gather the most relevant literature data about the characteristics and effects of the state of the skin barrier in rosacea. PMID:26982780

  5. Skin Cancer: Biology, Risk Factors & Treatment

    MedlinePlus

    ... turn Javascript on. Feature: Skin Cancer Skin Cancer: Biology, Risk Factors & Treatment Past Issues / Summer 2013 Table ... Articles Skin Cancer Can Strike Anyone / Skin Cancer: Biology, Risk Factors & Treatment / Timely Healthcare Checkup Catches Melanoma ...

  6. Echo: skin stress test

    NASA Technical Reports Server (NTRS)

    1960-01-01

    Skin Stress Test of the 12-foot satellite built as a prototype of the full-scale Echo satellite. The 12-foot diameter of the sphere was chosen because that was the ceiling height in the Langley model shop. The proposal to build the 12-foot satellite was made in November 1957. - Published in James R. Hansen, Spaceflight Revolution: NASA Langley Research Center From Sputnik to Apollo, NASA SP-4308, pp. 170-171.

  7. Skin toxicity of propranolol in guinea pigs.

    PubMed

    Kobayashi, I; Hosaka, K; Maruo, H; Saeki, Y; Kamiyama, M; Konno, C; Gemba, M

    1999-05-01

    The skin toxicities of propranolol were studied in guinea pigs. In the primary and cumulative skin irritation studies, the skin reactions and the histopathological changes were observed in all animals treated with propranolol, and those tended to increase with the increase of propranolol dosage. The skin reactions increased with the application times of propranolol up to 7 days in the cumulative skin irritation study. In the skin sensitization, the phototoxicity and the skin photosensitization studies, no skin reactions were observed in any animals used in the studies. These results indicate that propranolol caused skin irritation, but was negative for skin sensitization, phototoxicity and skin photosensitization in guinea pigs.

  8. [Skin reactions to bradykinin].

    PubMed

    Rihoux, J P; Ramboer, I; Fadel, R

    1995-10-01

    A large series of experiments carried out in animals and humans suggest that histamine release is not involved in the leakage phenomenon induced by bradykinin (BK) challenge. These experiments comprise in vitro studies on skin and bronchial human mast cells and in vivo studies on guinea pig airways and human skin using mepyramine, chlorpheniramine and terfenadine as reference H1-anti-histamines. Nevertheless, it has been shown recently that the H1 antagonist cetirizine 10 mg p.o. markedly inhibits skin reactions induced by BK challenge (intradermal injection of 212 micrograms BK in 10 microL saline and prick test with a solution of 21.2 micrograms/microL). In a guinea pig model, this drug also inhibited the bronchospasm induced by increasing concentrations of BK given by iv route (0.25 to 2 micrograms/Kg) and aerosol (3 to 300 micrograms/Kg). This inhibition was similar to the one obtained with the specific BK antagonist HOE 140 (15 pM/Kg). New data in the literature suggest the existence of various pharmacological mediators possibly involved in the BK-induced reaction: neuromediators, nitric oxyde and PAF. They also suggest that this reaction presents itself as a well defined sequence of pharmacological events. Since we could show that there is no binding of cetirizine to a human recombinant B2 receptor in vitro, some hypotheses are raised in order to explain this unexpected inhibiting effect of cetirizine.

  9. Fat in the skin

    PubMed Central

    Radner, Franz PW; Grond, Susanne; Haemmerle, Guenter; Lass, Achim

    2011-01-01

    Keratinocyte differentiation is essential for skin development and the formation of the skin permeability barrier. This process involves an orchestrated remodeling of lipids. The cleavage of precursor lipids from lamellar bodies by β-glucocerebrosidase, sphingomyelinase, phospholipases and sterol sulfatase generates ceramides, non-esterified fatty acids and cholesterol for the lipid-containing extracellular matrix, the lamellar membranes in the stratum corneum. The importance of triacylglycerol (TAG) hydrolysis for the formation of a functional permeability barrier was only recently appreciated. Mice with defects in TAG synthesis (acyl-CoA:diacylglycerol acyltransferase-2-knock-out) or TAG catabolism (comparative gene identification-58, -CGI-58-knock-out) develop severe permeability barrier defects and die soon after birth because of desiccation. In humans, mutations in the CGI-58 gene also cause (non-lethal) neutral lipid storage disease with ichthyosis. As a result of defective TAG synthesis or catabolism, humans and mice lack ω-(O)-acylceramides, which are essential lipid precursors for the formation of the corneocyte lipid envelope. This structure plays an important role in linking the lipid-enriched lamellar membranes to highly cross-linked corneocyte proteins. This review focuses on the current knowledge of biochemical mechanisms that are essential for epidermal neutral lipid metabolism and the formation of a functional skin permeability barrier. PMID:21695016

  10. Nanobubble Skin Supersolidity.

    PubMed

    Zhang, Xi; Liu, Xinjuan; Zhong, Yuan; Zhou, Zhaofeng; Huang, Yongli; Sun, Chang Q

    2016-11-01

    Water nanobubbles manifest fascinatingly higher mechanical strength, higher thermal stability, and longer lifetime than macroscopic bubbles; thus, they provide an important impact in applications in the biomedical and chemical industries. However, a detailed understanding of the mechanism behind these mysteries of nanobubbles remains a challenge. Consistency between quantum computations and Raman spectrometric measurements confirmed our predictions that a nanobubble skin shares the same supersolidity with molecular clusters, skins of bulk water, and water droplets because of molecular undercoordination (fewer than four nearest molecular neighbors). Molecular undercoordination (coordination number Zcluster < Zsurface < Zbubble < Zbulk = 4) shortens/extends the H-O/O:H bond and stiffens/softens its corresponding stretching phonons, whose frequency shift is proportional to the square root of the cohesive energy and inversely proportional to the segmental length. The strongly polarized O:H-O bond slows the molecular dynamics and increases the viscosity. The freezing temperature is lowered by the softened O:H bond, and the melting temperature is enhanced by the stiffened H-O bond. Therefore, the supersolid skin makes the nanobubbles thermally more stable, less dense, and stiffer and slows the dynamics of their molecular motion.

  11. Effect of Combination of Low-Frequency Sonophoresis or Electroporation with Iontophoresis on the Mannitol Flux or Electroosmosis through Excised Skin.

    PubMed

    Tokumoto, Seiji; Higo, Naruhito; Todo, Hiroaki; Sugibayashi, Kenji

    2016-01-01

    In vitro permeation studies of mannitol were conducted across excised hairless mouse skin to determine and compare the enhancing effect of electroporation (EP) or sonophoresis (SP) combined with iontophoresis (IP) on the electroosmotic flow, and to analyze the enhancement mechanism of these combined methods. Mannitol flux was utilized as an index for the electroosmotic flow due to its low molecular weight and no electrorepulsion effect. The combination of SP and IP (SP/IP) resulted in an apparent increase of electroosmotic flow (no effect was sometimes observed by SP/IP), while that of EP and IP (EP/IP) had no synergistic enhancing effect on the electroosmosis. Next, the combined effect of tape-stripping (TS) and IP (TS/IP) was examined in a similar manner to clarify the difference between the SP/IP and EP/IP effects on electroosmosis. When the TS number increased from 0 to 3, the electroosmotic flow increased with the TS number. However, no further increase was observed when the TS number became more than 3, and the flow started to decrease when the TS number became 5. The electric charge of the skin surface was then measured after SP or TS application. When SP was applied, the skin surface charge became much more negative and the electroosmotic flow by SP/IP was markedly increased. Thus, an increase in the electroosmotic flow across the skin during IP application can be obtained not by EP and TS, but by SP. The combined use of SP and IP is a promising means for the enhanced skin delivery of non-electrolyte drugs.

  12. "Skin facts" to optimize aesthetic outcomes.

    PubMed

    Brennan, Connie

    2015-01-01

    Aesthetic providers need to be well versed in the anatomy and intricacies of the skin. This foundational skin knowledge is critical in assessing clients' aged skin during the aesthetic consultation. A sound understanding of the skin is also a prerequisite to any facial rejuvenation procedure. This article provides the aesthetic provider with the basics of skin anatomy and how the skin changes over time.

  13. Enhancement of skin permeation of bufalin by limonene via reservoir type transdermal patch: formulation design and biopharmaceutical evaluation.

    PubMed

    Yang, Zhen; Teng, Yang; Wang, Hao; Hou, Huimin

    2013-04-15

    A reservoir-type transdermal delivery system (TDS) of bufalin was designed and evaluated for various formulation variables like different penetration enhancers, formulation matrix, rate controlling membranes as well as biopharmaceutical characteristics. Hairless mouse skin was used in permeation experiments with Franz diffusion cells. In vitro skin permeation study showed that terpenes, especially d-limonene was the most effective enhancer when ethanol and PG were used as the vehicle with a synergistic effect. Among different rate controlling membranes, ethylene vinyl acetate (EVA) membrane containing 19% vinyl acetate demonstrated a more suitable release rate for bufalin than the other membranes. In vivo pharmacokinetic study of the bufalin patch in rat showed steady-state of bufalin from 3h to 12 h. In vivo release rate and cumulative amount analyzed by deconvolution method demonstrated the sustained release of bufalin as long as the patch remained on the animal for at least 12 h. The MRT increased from 1h of IV administration to 9h of transdermal administration. In vitro permeation across mouse skin was found to have biphasic correlation with plasma AUC in the in vivo pharmacokinetic study. Current in vitro-in vivo correlation (IVIVC) enabled the prediction of pharmacokinetic profile of bufalin from in vitro permeation results. In conclusion, current reservoir transdermal patch containing 10% D-limonene as a permeation enhancer, 40% ethanol, 30% PG and 15% carbopol-water gel complex provided an improved sustained release of bufalin through transdermal administration. The bufalin patch was successfully applied to biopharmaceutical study in rats and demonstrated the feasibility of this transdermal formulation for future development and clinical trials.

  14. Absence of a p53 allele delays nitrogen mustard-induced early apoptosis and inflammation of murine skin.

    PubMed

    Inturi, Swetha; Tewari-Singh, Neera; Jain, Anil K; Roy, Srirupa; White, Carl W; Agarwal, Rajesh

    2013-09-15

    Bifunctional alkylating agent sulfur mustard (SM) and its analog nitrogen mustard (NM) cause DNA damage leading to cell death, and potentially activating inflammation. Transcription factor p53 plays a critical role in DNA damage by regulating cell cycle progression and apoptosis. Earlier studies by our laboratory demonstrated phosphorylation of p53 at Ser15 and an increase in total p53 in epidermal cells both in vitro and in vivo following NM exposure. To elucidate the role of p53 in NM-induced skin toxicity, we employed SKH-1 hairless mice harboring wild type (WT) or heterozygous p53 (p53+/-). Exposure to NM (3.2mg) caused a more profound increase in epidermal thickness and apoptotic cell death in WT relative to p53+/- mice at 24h. However, by 72h after exposure, there was a comparable increase in NM-induced epidermal cell death in both WT and p53+/- mice. Myeloperoxidase activity data showed that neutrophil infiltration was strongly enhanced in NM-exposed WT mice at 24h persisting through 72h of exposure. Conversely, robust NM-induced neutrophil infiltration (comparable to WT mice) was seen only at 72h after exposure in p53+/- mice. Similarly, NM-exposure strongly induced macrophage and mast cell infiltration in WT, but not p53+/- mice. Together, these data indicate that early apoptosis and inflammation induced by NM in mouse skin are p53-dependent. Thus, targeting this pathway could be a novel strategy for developing countermeasures against vesicants-induced skin injury.

  15. Modulation of electroosmosis and flux through skin: effect of propylene glycol.

    PubMed

    Lee, Seung Yeon; Jeong, Na Young; Oh, Seaung Youl

    2014-04-01

    The effect of propylene glycol (PG) on transdermal flux under current was investigated using conventional in vitro iontophoresis methodology. The results were evaluated to explain how PG affects the electroosmotic volume flow (EVF) and electromigrational flux through skin. As a marker molecule for the direction and magnitude of EVF, a non-charged neutral molecule, acetaminophen (AAP), was used. At pH 7.4, the direction of EVF was from anode to cathode. During anodal and cathodal current application, PG decreased AAP flux and this decrease was proportional to the concentration of PG, indicating that the presence of PG in the medium decreased the EVF. This decrease is likely due to the decrease in dielectric constant of the medium and the increases in medium viscosity by the addition of PG. The increase in AAP solubility and the viscosity of the medium by PG may also contribute to the decrease in diffusional flux. The magnitude of EVF was estimated to be about 4.2 μl/cm(2 )h. The effect of PG on the flux of a positively charged drug, donepezil hydrochloride (DH), was further investigated using pH 4.6 phosphate buffer solution. The permselectivity of skin in this solution was also investigated and revealed that the isoelectric point of hairless mouse skin is higher than pH 4.6. Anodal delivery showed much higher flux than cathodal and passive flux, indicating that electromigration is playing the major role for DH flux. As the concentration of PG increased, anodal flux of DH decreased. The main reason for this decrease in electromigration is likely due to the increase in medium viscosity. These results and discussions clearly suggest that the incorporation of frequently used organic cosolvents and penetration enhancers into the iontophoretic formulation should be carefully chosen with a thorough investigation for their effect on flux. Overall, these results provided further mechanistic insights into the role of electroosmosis and electromigration in flux across skin

  16. Skin moisturization mechanisms: new data.

    PubMed

    Bonté, F

    2011-05-01

    The main function of the skin is to protect the body against exogenous substances and excessive water loss. The skin barrier is located in the outermost layer of the skin, called the stratum corneum, which is composed of corneocytes, originating from the keratinocytes differentiation process, embedded in organized complex lipid domains. Moisturizing of the skin is recognized as the first anti-aging skin care. Skin moisturization is essential for its appearance, protection, complexion, softness and the reinforcement of its barrier properties against deleterious and exogenous environmental factors. The intrinsic water binding capacity of skin is not only due to the complex natural moisturizing factor present in corneocytes, but also to hyaluronic acid and a regulated water transport within the skin. Recent data shows that the water movements between the cells at the different levels of the epidermis are due to dedicated water and glycerol transport proteins named aquaporins. Their role in the skin moisturization is completed by corneodesmosomes and tight junctions. Water and pH are now shown to be of prime importance in the regulation of the epidermal enzymes linked to corneocytes desquamation and lipid synthesis. Furthermore, the level of moisturization of the skin is important in its protection against repeated exposure to various irritant agents or phenomena such as very frequent washing with strong tensioactive materials.

  17. Epidemiology of skin cancer.

    PubMed

    Leiter, Ulrike; Eigentler, Thomas; Garbe, Claus

    2014-01-01

    Melanoma and nonmelanoma skin cancer (NMSC) are now the most common types of cancer in white populations. Both tumor entities show an increasing incidence rate worldwide but a stable or decreasing mortality rate. NMSC is the most common cancer in white-skinned individuals with a worldwide increasing incidence. NMSC is an increasing problem for health care services worldwide which causes significant morbidity. The rising incidence rates of NMSC are probably caused by a combination of increased exposure to ultraviolet (UV) or sun light, increased outdoor activities, changes in clothing style, increased longevity, ozone depletion, genetics and in some cases, immune suppression. An intensive UV exposure in childhood and adolescence was causative for the development of basal cell carcinoma (BCC) whereas for the etiology of SCC a chronic UV exposure in the earlier decades was accused. Cutaneous melanoma is the most rapidly increasing cancer in white populations, in the last 3 decades incidence rates have risen up to 5-fold. In 2008 melanoma was on place 5 in women and on place 8 in men of the most common solid tumor entities in Germany. The frequency of its occurrence is closely associated with the constitutive color of the skin, and the geographical zone. Changes in outdoor activities and exposure to sunlight during the past 50 years are an important factor for the increasing incidence of melanoma. Mortality rates of melanoma show a stabilization in the USA, Australia and also in European countries. In contrast to SCC, melanoma risk seems to be associated with an intermittent exposure to sunlight. Prevention campaigns aim on reducing incidence and achieving earlier diagnosis, which resulted in an ongoing trend toward thin melanoma since the last two decades. However, the impact of primary prevention measures on incidence rates of melanoma is unlikely to be seen in the near future, rather increasing incidence rates to 40-50/100,000 inhabitants/year should be expected in

  18. Climate change and skin.

    PubMed

    Balato, N; Ayala, F; Megna, M; Balato, A; Patruno, C

    2013-02-01

    Global climate appears to be changing at an unprecedented rate. Climate change can be caused by several factors that include variations in solar radiation received by earth, oceanic processes (such as oceanic circulation), plate tectonics, and volcanic eruptions, as well as human-induced alterations of the natural world. Many human activities, such as the use of fossil fuel and the consequent accumulation of greenhouse gases in the atmosphere, land consumption, deforestation, industrial processes, as well as some agriculture practices are contributing to global climate change. Indeed, many authors have reported on the current trend towards global warming (average surface temperature has augmented by 0.6 °C over the past 100 years), decreased precipitation, atmospheric humidity changes, and global rise in extreme climatic events. The magnitude and cause of these changes and their impact on human activity have become important matters of debate worldwide, representing climate change as one of the greatest challenges of the modern age. Although many articles have been written based on observations and various predictive models of how climate change could affect social, economic and health systems, only few studies exist about the effects of this change on skin physiology and diseases. However, the skin is the most exposed organ to environment; therefore, cutaneous diseases are inclined to have a high sensitivity to climate. For example, global warming, deforestation and changes in precipitation have been linked to variations in the geographical distribution of vectors of some infectious diseases (leishmaniasis, lyme disease, etc) by changing their spread, whereas warm and humid environment can also encourage the colonization of the skin by bacteria and fungi. The present review focuses on the wide and complex relationship between climate change and dermatology, showing the numerous factors that are contributing to modify the incidence and the clinical pattern of many

  19. Influence of the treatment protocol upon the in vivo efficacy of cidofovir (HPMPC) and of acyclovir (ACV) formulations in topical treatment of cutaneous HSV-1 infection in hairless mice.

    PubMed

    Afouna, M I; Mehta, S C; Ghanem, A H; Higuchi, W I; Kern, E R; DeClercq, E; El-Shattawy, H H

    1999-05-01

    In recent studies we found that the topical effectiveness of acyclovir (ACV) formulations was a single-valued function of C-the target site free drug concentration. The topical efficacy was the same when the therapy was initiated 0, 1, or 2 days after intracutaneous herpes simplex virus type-1 (HSV-1) inoculation in hairless mice. The purpose of the present study was to examine the hypothesis that the topical effectiveness of cidofovir (HPMPC) would not be a single valued function of C and that it would be dependent upon when the therapy was initiated relative to the time of viral infection. Formulations of HPMPC and ACV in 95% DMSO as a vehicle were used. Hairless mice intracutaneously infected with HSV-1 were used, and 20 microL of the test formulation was topically applied twice a day. In protocol A, the treatment was continued until the fourth day after virus inoculation, whereas in protocol B the treatment was terminated on the day of virus inoculation. Treatment was initiated on various days ranging from day -6 to day 4, and the lesions were scored on day 5. Treatment of ACV according to protocol A proved efficacious whether started as early as 6 days before virus inoculation or later, whereas the efficacy of ACV was annihilated if applied following protocol B. For HPMPC, on the other hand, the in vivo efficacies were found to be strongly dependent on how early the therapy was initiated, and significant efficacy was observed even when the treatment was terminated on the day of virus inoculation. This difference was attributed to the virus-independent intracellular phosphorylation of HPMPC and slow clearance of its metabolites from the cell. It was also noted that, similar to ACV, for HPMPC the topical efficacy is likely to be a function of C for a fixed protocol. However, unlike for ACV, for HPMPC the efficacy was not a single-valued function of C.

  20. Nonmelanoma skin cancer.

    PubMed

    Dubas, Lauren E; Ingraffea, Adam

    2013-02-01

    Nonmelanoma skin cancer (NMSC) is the most common form of malignancy in humans. The incidence of NMSC continues to increase despite increased awareness and sun-protective measures. If neglected or mismanaged, NMSC can cause significant morbidity and even death. The most common forms of NMSC on the head and neck include basal cell carcinoma, squamous cell carcinoma, sebaceous carcinoma, eccrine porocarcinoma, Merkel cell carcinoma, atypical fibroxanthoma, and microcystic adnexal carcinoma. Surgery is the mainstay of treatment (standard excision, Mohs micrographic surgery, curettage); however, other modalities exist, including radiation, topical immunomodulators, photodynamic therapy, and new systemic medications.

  1. Low temperature skin treatment

    NASA Astrophysics Data System (ADS)

    Klipping, G.; Krishna, A.; Ruppert, U.; Srinivasan, R.; Walter, H.

    Although freezing has been a successful method of curing various kinds of skin lesions for at least 80 years, little progress has been made regarding the techniques and instruments available to the dermatoligist for applying cold. The attempts to improve this technique are reviewed, and the requirements is for successful cryotreatment are discussed taking warts as an example. With these requirements in mind, a simple and effective cryoprobe has been developed by the authors. Its design is described, and the experiences from a year's routine application of the probe to the treatment of warts are discussed.

  2. Is skin penetration a determining factor in skin sensitization ...

    EPA Pesticide Factsheets

    Summary:Background. It is widely accepted that substances that cannot penetrate through the skin will not be sensitisers. Thresholds based on relevant physicochemical parameters such as a LogKow > 1 and a MW 1 is a true requirement for sensitisation.Methods. A large dataset of substances that had been evaluated for their skin sensitisation potential, together with measured LogKow values was compiled from the REACH database. The incidence of skin sensitisers relative to non-skin sensitisers below and above the LogKow = 1 threshold was evaluated. Results. 1482 substances with associated skin sensitisation outcomes and measured LogKow values were identified. 305 substances had a measured LogKow < 0 and of those, 38 were sensitisers.Conclusions. There was no significant difference in the incidence of skin sensitisation above and below the LogKow = 1 threshold. Reaction chemistry considerations could explain the skin sensitisation observed for the 38 sensitisers with a LogKow < 0. The LogKow threshold is a self-evident truth borne out from the widespread misconception that the ability to efficiently penetrate the stratum corneum is a key determinant of skin sensitisation potential and potency. Using the REACH data extracted to test out the validity of common assumptions in the skin sensitization AOP. Builds on trying to develop a proof of concept IATA

  3. Singlet oxygen luminescence as an in vivo photodynamic therapy dose metric: validation in normal mouse skin with topical amino-levulinic acid

    PubMed Central

    Niedre, M J; Yu, C S; Patterson, M S; Wilson, B C

    2005-01-01

    Although singlet oxygen (1O2) has long been proposed as the primary reactive oxygen species in photodynamic therapy (PDT), it has only recently been possible to detect it in biological systems by its luminescence at 1270 nm. Having previously demonstrated this in vitro and in vivo, we showed that cell survival was strongly correlated to the 1O2 luminescence in cell suspensions over a wide range of treatment parameters. Here, we extend this to test the hypothesis that the photobiological response in vivo is also correlated with 1O2 generation, independent of individual treatment parameters. The normal skin of SKH1-HR hairless mice was sensitised with 20% amino-levulinic acid-induced protoporophyrin IX and exposed to 5, 11, 22 or 50 J cm−2 of pulsed 523 nm light at 50 mW cm−2, or to 50 J cm−2 at 15 or 150 mW cm−2. 1O2 luminescence was measured during treatment and the photodynamic response of the skin was scored daily for 2 weeks after treatment. As observed by other authors, a strong irradiance dependence of the PDT effect was observed. However, in all cases the responses increased with the 1O2 luminescence, independent of the irradiance, demonstrating for the first time in vivo an unequivocal mechanistic link between 1O2 generation and photobiological response. PMID:15655542

  4. Dietary Cerebroside from Sea Cucumber (Stichopus japonicus): Absorption and Effects on Skin Barrier and Cecal Short-Chain Fatty Acids.

    PubMed

    Duan, Jingjing; Ishida, Marina; Aida, Kazuhiko; Tsuduki, Tsuyoshi; Zhang, Jin; Manabe, Yuki; Hirata, Takashi; Sugawara, Tatsuya

    2016-09-21

    Sphingolipids from marine sources have attracted more attention recently because of their distinctive structures and expected functions. In this study, the content and components of cerebroside from sea cucumber Stichopus japonicus were analyzed. The absorption of cerebroside from S. japonicus was investigated with an in vivo lipid absorption assay. The result revealed that S. japonicus is a rich source of cerebroside that contained considerable amounts of odd carbon chain sphingoid bases. The cumulative recoveries of d17:1- and d19:2-containing cerebrosides were 0.31 ± 0.16 and 0.32 ± 0.10%, respectively, for 24 h after administration. To the best of the authors' knowledge, this is the first work that shows sphingolipids from a marine source could be absorbed in vivo and incorporated into ceramides. In addition, dietary supplementation with sea cucumber cerebroside to hairless mouse improved the skin barrier function and increased short-chain fatty acids in cecal contents, which have shown beneficial effects on the host.

  5. Penetration enhancement in mouse skin and lipolysis in adipocytes by TAT-GKH, a new cosmetic ingredient.

    PubMed

    Lim, Jun Man; Chang, Min Youl; Park, Sun Gyoo; Kang, Nae Gyu; Song, Young Sook; Lee, Young Hwa; Yoo, Young Chang; Cho, Wan Goo; Choi, Soo Young; Kang, She Hoon

    2003-01-01

    Since the basic domain of human immunodeficiency virus type I (HIV-1) transactivator of transcription (TAT) protein was reported to possess the ability to traverse biological membranes efficiently, various therapeutic proteins have been attached to TAT for the purpose of therapy. In this study, the tripeptide GKH (glycine-lysine-histidine) derived from parathyroid hormone (PTH), known as lipolytic peptide, was attached to 9-poly lysine (TAT) to be used as a cosmetic ingredient in slimming products. TAT-GKH at 10(-5) M induced approximately 37.6% and 41.5% maximal lipolytic effects in cultured 3T3-L1 differentiated adipocytes and in epididymal adipocytes isolated from rats, respectively, compared with basal lipolysis. The lipolytic effect of GKH was not changed by TAT-GKH fusion. In cytotoxicity tests, there was no cytotoxicity in any dose concentration of TAT-GKH. We confirmed that TAT-GKH induced lipolytic activity by GKH without cytotoxicity and with the possibility of its use as a safe cosmetic ingredient. TAT-GKH elevated penetration into excised hairless mice skin 36 times more efficiently than GKH. TAT-GKH can be used as a cosmetic ingredient in slimming products, with both penetration enhancement and lipolytic effect without cytotoxicity.

  6. [Youth Healthcare guideline 'Skin disorders'].

    PubMed

    Deurloo, Jacqueline A; van Gameren-Oosterom, Helma B M; Kamphuis, Mascha

    2012-01-01

    There is a high incidence of skin disorders; these are also frequently encountered within Youth Healthcare (YHC). Some skin disorders are caused by an underlying disease, syndrome or child abuse. Therefore, detection of these causes in an early stage is important. Skin disorders can have a huge psychosocial impact on both child and parents. This is one of the reasons why prevention, detection, diagnosis, treatment, referral, and uniform advice and guidance are of great importance. The YHC Guideline examines counselling and advice, criteria for referral to primary or secondary healthcare, and skincare in general. It also describes the disorders that should be actively detected. The Guideline also looks at specific aspects of dark skins and ethnic diversity, and the impact of skin disorders on general wellbeing. The accompanying web-based tool includes argumentation and opinions from experts on more than 75 skin disorders, including illustrations and decision trees, to aid the drawing up of a treatment plan.

  7. Pathophysiological Study of Sensitive Skin.

    PubMed

    Buhé, Virginie; Vié, Katell; Guéré, Christelle; Natalizio, Audrey; Lhéritier, Céline; Le Gall-Ianotto, Christelle; Huet, Flavien; Talagas, Matthieu; Lebonvallet, Nicolas; Marcorelles, Pascale; Carré, Jean-Luc; Misery, Laurent

    2016-03-01

    Sensitive skin is a clinical syndrome characterized by the occurrence of unpleasant sensations, such as pruritus, burning or pain, in response to various factors, including skincare products, water, cold, heat, or other physical and/or chemical factors. Although these symptoms suggest inflammation and the activation of peripheral innervation, the pathophysiogeny of sensitive skin remains unknown. We systematically analysed cutaneous biopsies from 50 healthy women with non-sensitive or sensitive skin and demonstrated that the intraepidermal nerve fibre density, especially that of peptidergic C-fibres, was lower in the sensitive skin group. These fibres are involved in pain, itching and temperature perception, and their degeneration may promote allodynia and similar symptoms. These results suggest that the pathophysiology of skin sensitivity resembles that of neuropathic pruritus within the context of small fibre neuropathy, and that environmental factors may alter skin innervation.

  8. Advanced therapies of skin injuries.

    PubMed

    Maver, Tina; Maver, Uroš; Kleinschek, Karin Stana; Raščan, Irena Mlinarič; Smrke, Dragica Maja

    2015-12-01

    The loss of tissue is still one of the most challenging problems in healthcare. Efficient laboratory expansion of skin tissue to reproduce the skins barrier function can make the difference between life and death for patients with extensive full-thickness burns, chronic wounds, or genetic disorders such as bullous conditions. This engineering has been initiated based on the acute need in the 1980s and today, tissue-engineered skin is the reality. The human skin equivalents are available not only as models for permeation and toxicity screening, but are frequently applied in vivo as clinical skin substitutes. This review aims to introduce the most important recent development in the extensive field of tissue engineering and to describe already approved, commercially available skin substitutes in clinical use.

  9. [Sensitive skin: a complex syndrome].

    PubMed

    Escalas-Taberner, J; González-Guerra, E; Guerra-Tapia, A

    2011-10-01

    Epidemiologic studies indicate that ever larger numbers of people report having sensitive skin, for which a European prevalence of 50% is estimated. Sensitive skin is characterized by hyperreactivity, with manifestations varying in relation to many factors. The pathogenesis of this disorder is poorly understood, although studies point to a biophysical mechanism. Objective diagnosis of sensitive skin is difficult, as information comes mainly from the patient's report of symptoms in the absence of effective, strongly predictive tests because of great interindividual variability in skin sensitivity. Substances that trigger a reaction in hypersensitive skin also vary greatly. The impact of this syndrome on quality of life is considerable and patients often present psychiatric symptoms; therefore, dermatologists should explore this possibility when taking a patient's history. Patient cooperation and physician persistence are both essential for treating sensitive skin.

  10. Neuroendocrine System of the Skin

    PubMed Central

    Slominski, Andrzej

    2005-01-01

    Evidence is accumulating that the skin can serve as a peripheral neuroendocrine organ. The skin neuroendocrine activities are predominantly independent of regulation from the central level (which controls classical hormone secretion) but are rather regulated by local cutaneous factors. These endocrine factors would represent an exquisite regulatory layer addressed at restricting maximally the effect of noxious agents in the skin to preserve local and consequently global homeostasis. PMID:16205064

  11. Fetal skin wound healing.

    PubMed

    Buchanan, Edward P; Longaker, Michael T; Lorenz, H Peter

    2009-01-01

    The developing fetus has the ability to heal wounds by regenerating normal epidermis and dermis with restoration of the extracellular matrix (ECM) architecture, strength, and function. In contrast, adult wounds heal with fibrosis and scar. Scar tissue remains weaker than normal skin with an altered ECM composition. Despite extensive investigation, the mechanism of fetal wound healing remains largely unknown. We do know that early in gestation, fetal skin is developing at a rapid pace and the ECM is a loose network facilitating cellular migration. Wounding in this unique environment triggers a complex cascade of tightly controlled events culminating in a scarless wound phenotype of fine reticular collagen and abundant hyaluronic acid. Comparison between postnatal and fetal wound healing has revealed differences in inflammatory response, cellular mediators, cytokines, growth factors, and ECM modulators. Investigation into cell signaling pathways and transcription factors has demonstrated differences in secondary messenger phosphorylation patterns and homeobox gene expression. Further research may reveal novel genes essential to scarless repair that can be manipulated in the adult wound and thus ameliorate scar.

  12. Fractional laser skin resurfacing.

    PubMed

    Alexiades-Armenakas, Macrene R; Dover, Jeffrey S; Arndt, Kenneth A

    2012-11-01

    Laser skin resurfacing (LSR) has evolved over the past 2 decades from traditional ablative to fractional nonablative and fractional ablative resurfacing. Traditional ablative LSR was highly effective in reducing rhytides, photoaging, and acne scarring but was associated with significant side effects and complications. In contrast, nonablative LSR was very safe but failed to deliver consistent clinical improvement. Fractional LSR has achieved the middle ground; it combined the efficacy of traditional LSR with the safety of nonablative modalities. The first fractional laser was a nonablative erbium-doped yttrium aluminum garnet (Er:YAG) laser that produced microscopic columns of thermal injury in the epidermis and upper dermis. Heralding an entirely new concept of laser energy delivery, it delivered the laser beam in microarrays. It resulted in microscopic columns of treated tissue and intervening areas of untreated skin, which yielded rapid reepithelialization. Fractional delivery was quickly applied to ablative wavelengths such as carbon dioxide, Er:YAG, and yttrium scandium gallium garnet (2,790 nm), providing more significant clinical outcomes. Adjustable laser parameters, including power, pitch, dwell time, and spot density, allowed for precise determination of percent surface area, affected penetration depth, and clinical recovery time and efficacy. Fractional LSR has been a significant advance to the laser field, striking the balance between safety and efficacy.

  13. [Radiotherapy of skin cancers].

    PubMed

    Hennequin, C; Rio, E; Mahé, M-A

    2016-09-01

    The indications of radiotherapy for skin cancers are not clearly defined because of the lack of randomised trials or prospective studies. For basal cell carcinomas, radiotherapy frequently offers a good local control, but a randomized trial showed that surgery is more efficient and less toxic. Indications of radiotherapy are contra-indications of surgery for patients older than 60, non-sclerodermiform histology and occurring in non-sensitive areas. Adjuvant radiotherapy could be proposed to squamous cell carcinomas, in case of poor prognostic factors. Dose of 60 to 70Gy are usually required, and must be modulated to the size of the lesions. Adjuvant radiotherapy seems beneficial for desmoplastic melanomas but not for the other histological types. Prophylactic nodal irradiation (45 to 50Gy), for locally advanced tumours (massive nodal involvement), decreases the locoregional failure rate but do not increase survival. Adjuvant radiotherapy (50 to 56Gy) for Merckel cell carcinomas increases also the local control rate, as demonstrated by meta-analysis and a large epidemiological study. Nodal areas must be included, if there is no surgical exploration (sentinel lymph node dissection). Kaposi sarcomas are radiosensitive and could be treated with relatively low doses (24 to 30Gy). Also, cutaneous lymphomas are good indications for radiotherapy: B lymphomas are electively treated with limited fields. The role of total skin electron therapy for T-lymphomas is still discussed; but palliative radiotherapy is very efficient in case of cutaneous nodules.

  14. Skin flaps in reconstructive surgery.

    PubMed

    Pavletic, M M

    1990-01-01

    A skin flap (pedicle graft) is a partially detached segment of skin and subcutaneous tissue that includes a blood supply essential to its survival. As a result, skin flaps are capable of closing a variety of defects, including poorly vascularized wound beds that are incapable of maintaining free grafts. In many cases, skin flaps can bypass economically many of the potential problems associated with healing by second intention. This article presents an overview of pedicle grafts, with emphasis on the clinical use of local flap techniques.

  15. Travel-associated skin disease.

    PubMed

    Morris-Jones, Rachael; Morris-Jones, Stephen

    2012-09-01

    Travel associated skin disease is extremely common and a frequent cause of the returning traveller seeking medical attention. Widespread cutaneous eruptions usually represent reactive rashes, indicating an underlying systemic infection or allergic reaction. Patients with disseminated or spreading rashes following travel often present with fever and malaise. In contrast, those presenting with localised skin disease such as a blister, nodule, plaque, ulcer etc are usually well in themselves but have sustained a bite/sting/penetrating injury or introduction of infection directly into the skin at the affected site. As a general rule widespread rashes are investigated with blood tests/serology and localised lesions with a skin biopsy for culture and histology.

  16. Treatments Improving Skin Barrier Function.

    PubMed

    Lodén, Marie

    2016-01-01

    Moisturizers affect the stratum corneum architecture and barrier homeostasis, i.e. topically applied ingredients are not as inert to the skin as one might expect. A number of different mechanisms behind the barrier-influencing effects of moisturizers have been suggested, such as simple deposition of lipid material outside the skin. Ingredients in the moisturizers may also change the lamellar organization and the packing of the lipid matrix and thereby skin permeability. Topically applied substances may also penetrate deeper into the skin and interfere with the production of barrier lipids and the maturation of corneocytes. Furthermore, moisturizing creams may influence the desquamatory proteases and alter the thickness of the stratum corneum.

  17. Skin decontamination: principles and perspectives.

    PubMed

    Chan, Heidi P; Zhai, Hongbo; Hui, Xiaoying; Maibach, Howard I

    2013-11-01

    Skin decontamination is the primary intervention needed in chemical, biological and radiological exposures, involving immediate removal of the contaminant from the skin performed in the most efficient way. The most readily available decontamination system on a practical basis is washing with soap and water or water only. Timely use of flushing with copious amounts of water may physically remove the contaminant. However, this traditional method may not be completely effective, and contaminants left on the skin after traditional washing procedures can have toxic consequences. This article focuses on the principles and practices of skin decontamination.

  18. Oral administration of caffeine during voluntary exercise markedly decreases tissue fat and stimulates apoptosis and cyclin B1 in UVB-treated skin of hairless p53-knockout mice.

    PubMed

    Lou, Yourong; Peng, Qingyun; Nolan, Bonnie; Wagner, George C; Lu, Yaoping

    2010-04-01

    Treatment of p53(-/-) mice orally with caffeine, voluntary exercise or their combination for 2 weeks prior to a single irradiation with UVB (i) decreased the weight of the epididymal fat pads by 22, 40 and 56%, (ii) decreased the thickness of the dermal fat layer by 10, 26 and 42%, (iii) increased the number of apoptotic sunburn cells by 29, 100 and 489%, (iv) increased the number of caspase-3-positive cells by 33, 117 and 667% and (v) increased the number of mitotic cells with cyclin B1-positive staining by 40, 210 and 510%, respectively. Pearson's correlation coefficient indicated a statistically significant inverse relationship between the level of tissue fat and the number of mitotic cells with cyclin B1 in p53(-/-) mice but not in p53(+/+) littermates. Western blot analysis indicated that treatment of p53(-/-) mice with caffeine together with exercise increased the level of cyclin B1 significantly more than in p53(+/+) mice. p53(-/-) mice, but not p53(+/+) mice, treated with caffeine during exercise exhibited a dramatic decrease in the level of survivin. Our results suggest that voluntary exercise in combination with oral caffeine may exert a synergistic increase in UVB-induced apoptosis and that tissue fat may be a more important modulator of apoptosis and carcinogenesis in p53-deficient mice than in p53-normal mice. The stimulatory effects on apoptosis in p53(-/-) mice by the combination treatment might be associated with increased levels of cyclin B1 and decreased levels of survivin.

  19. [Caring for perilesional skin or skin having a lesion risk].

    PubMed

    Segovia, Gómez T; Javares, Curto T; Barahona, M; Verdú, Soriano J

    2007-10-01

    In order to increase the clinical and scientific evidence of the Hyperoxygenated Fatty Acids (HFA) in emulsion preparation for skin care, this study considers to evaluate prospectively how it influences in the state of the periwound skin (when there are active lesions) or in which it presents a high risk of lesion production.

  20. Pomegranate fruit extract inhibits UVB-induced inflammation and proliferation by modulating NF-κB and MAPK signaling pathways in mouse skin.

    PubMed

    Khan, Naghma; Syed, Deeba N; Pal, Harish Chandra; Mukhtar, Hasan; Afaq, Farrukh

    2012-01-01

    There is considerable interest in the identification of natural agents capable of affording protection to skin from the adverse effects of solar ultraviolet B (UVB) radiation. Pomegranate (Punica granatum L.) fruit possesses as strong antioxidant, anti-inflammatory and antiproliferative properties. Recently, we have shown that oral feeding of pomegranate fruit extract (PFE) to mice afforded substantial protection from the adverse effects of single UVB radiation via modulation in early biomarkers of photocarcinogenesis. This study was designed to investigate the photochemopreventive effects of PFE (0.2%, wt/vol) after multiple UVB irradiations (180 mJ cm(-2), on alternative day, for a total of seven treatments) to the skin of SKH-1 hairless mice. Oral feeding of PFE to SKH-1 mice inhibited UVB-induced epidermal hyperplasia, infiltration of leukocytes, protein oxidation and lipid peroxidation. Immunoblot analysis demonstrated that oral feeding of PFE to mice inhibited UVB-induced (1) nuclear translocation and phosphorylation of nuclear factor kappa B/p65, (2) phosphorylation and degradation of IκBα, (3) activation of IKKα/ΙΚΚβ and (4) phosphorylation of mitogen-activated protein kinase proteins and c-Jun. PFE consumption also inhibited UVB-induced protein expression of (1) COX-2 and iNOS, (2) PCNA and cyclin D1 and (3) matrix metalloproteinases-2,-3 and -9 in mouse skin. Taken together, these data show that PFE consumption afforded protection to mouse skin against the adverse effects of UVB radiation by modulating UVB-induced signaling pathways.

  1. Characteristics of the Aging Skin

    PubMed Central

    Farage, Miranda A.; Miller, Kenneth W.; Elsner, Peter; Maibach, Howard I.

    2013-01-01

    Significance Although most researches into the changes in skin with age focus on the unwelcome aesthetic aspects of the aging skin, skin deterioration with age is more than a merely cosmetic problem. Although mortality from skin disease is primarily restricted to melanoma, dermatological disorders are ubiquitous in older people with a significant impact on quality of life. The structural and functional deterioration of the skin that occurs with age has numerous clinical presentations, ranging from benign but potentially excruciating disorders like pruritus to the more threatening carcinomas and melanomas. Recent Advances The degenerative changes that occur in the aging skin are increasingly understood at both the molecular and cellular level, facilitating a deeper understanding of the structural and functional deterioration that these changes produce. Critical Issues A loss of both function and structural stability in skin proceeds unavoidably as individuals age, which is the result of both intrinsic and extrinsic processes, which contribute simultaneously to a progressive loss of skin integrity. Intrinsic aging proceeds at a genetically determined pace, primarily caused by the buildup of damaging products of cellular metabolism as well as an increasing biological aging of the cells. Estrogen levels strongly influence skin integrity in women as well; falling levels in midlife, therefore, produce premature aging as compared with similarly aged men. Extrinsic insults from the environment add to the dermatological signs of aging. Future Directions A deeper understanding of the physiological basis of skin aging will facilitate progress in the treatment of the unwelcome sequelae of aging skin, both cosmetic and pathogenic. PMID:24527317

  2. Monogenic human skin disorders.

    PubMed

    Lemke, Johannes R; Kernland-Lang, Kristin; Hörtnagel, Konstanze; Itin, Peter

    2014-01-01

    Human genodermatoses represent a broad and partly confusing spectrum of countless rare diseases with confluent and overlapping phenotypes often impeding a precise diagnosis in an affected individual. High-throughput sequencing techniques have expedited the identification of novel genes and have dramatically simplified the establishment of genetic diagnoses in such heterogeneous disorders. The precise genetic diagnosis of a skin disorder is crucial for the appropriate counselling of patients and their relatives regarding the course of the disease, prognosis and recurrence risks. Understanding the underlying pathophysiology is a prerequisite to understanding the disease and developing specific, targeted or individualized therapeutic approaches. We aimed to create a comprehensive overview of human genodermatoses and their respective genetic aetiology known to date. We hope this may represent a useful tool in guiding dermatologists towards genetic diagnoses, providing patients with individual knowledge on the respective disorder and applying novel research findings to clinical practice.

  3. The peeling skin syndrome.

    PubMed

    Levy, S B; Goldsmith, L A

    1982-11-01

    A unique form of congenital ichthyosis in two unrelated patients is described and characterized histologically by separation of the epidermis between the stratum corneum and the stratum granulosum. The clinical history, genetics, serially performed skin biopsies, and biochemical studies are reviewed. This form of ichthyosis is different from previously described entities. Lifelong peeling of the general body epidermis, pruritus, short stature, easily removed anagen hairs, and the ability to easily mechanically separate stratum corneum from the rest of the epidermis characterize the syndrome. In two families with this disorder, autosomal recessive inheritance is suggested. A low plasma tryptophan level as present in two patients with this disease. This inherited disorder of the epidermis was first described in 1924 before the genetics and histology of ichthyosis were extensively studied and is a distinct genetic and clinical entity to be considered in unusual cases of ichthyosis.

  4. Ablative skin resurfacing.

    PubMed

    Chwalek, Jennifer; Goldberg, David J

    2011-01-01

    Ablative skin resurfacing has remained the gold standard for treating photodamage and acne scars since the development of the first CO(2) lasers. CO(2) and Er:YAG lasers emit infrared light, which targets water resulting in tissue contraction and collagen formation. The first ablative laser systems created significant thermal damage resulting in unacceptably high rates of scarring and prolonged healing. Newer devices, such as high-energy pulsed lasers and fractional ablative lasers, are capable of achieving significant improvements with fewer side effects and shorter recovery times. While ablative resurfacing has become safer, careful patient selection is still important to avoid post-treatment scarring, dyspigmentation, and infections. Clinicians utilizing ablative devices need to be aware of possible side effects in order to maximize results and patient satisfaction. This chapter reviews the background of ablative lasers including the types of ablative lasers, mechanism of action, indications for ablative resurfacing, and possible side effects.

  5. The Sensitive Skin Syndrome

    PubMed Central

    Lev-Tov, Hadar; Maibach, Howard I

    2012-01-01

    Sensitive skin syndrome (SSS) is a common and challenging condition, yet little is known about its underlying pathophysiology. Patients with SSS often present with subjective complaints of severe facial irritation, burning, and/or stinging after application of cosmetic products. These complaints are out of proportion to the objective clinical findings. Defined as a self-diagnosed condition lacking any specific objective findings, SSS is by definition difficult to quantify and, therefore, the scientific community has yet to identify an acceptable objective screening test. In this overview we review recent epidemiological studies, present current thinking on the pathophysiology leading to SSS, discuss the challenges SSS presents, and recommend a commonsense approach to management. PMID:23248357

  6. Evaluation of EpiDerm full thickness-300 (EFT-300) as an in vitro model for skin irritation: studies on aliphatic hydrocarbons.

    PubMed

    Mallampati, Ramya; Patlolla, Ram R; Agarwal, Saurab; Babu, R Jayachandra; Hayden, Patrick; Klausner, Mitchell; Singh, Mandip S

    2010-03-01

    The aim of this study was to understand the skin irritation effects of saturated aliphatic hydrocarbons (HCs), C9-C16, found jet fuels using in vitro 3-dimensional EpiDerm full thickness-300 (EFT-300) skin cultures. The EFT-300 cultures were treated with 2.5microl of HCs and the culture medium and skin samples were collected at 24 and 48h to measure the release of various inflammatory biomarkers (IL-1alpha, IL-6 and IL-8). To validate the in vitro results, in vivo skin irritation studies were carried out in hairless rats by measuring trans epidermal water loss (TEWL) and erythema following un-occlusive dermal exposure of HCs for 72h. The MTT tissue viability assay results with the EFT-300 tissue show that 2.5microl/tissue ( approximately 4.1microl/cm(2)) of the HCs did not induce any significant changes in the tissue viability for exposure times up to 48h of exposure. Microscopic observation of the EFT-300 cross-sections indicated that there were no obvious changes in the tissue morphology of the samples at 24h, but after 48h of exposure, tridecane, tetradecane and hexadecane produced a slight thickening and disruption of stratum corneum. Dermal exposures of C12-C16 HCs for 24h significantly increased the expression of IL-1alpha in the skin as well as in the culture medium. Similarly, dermal exposure of all HCs for 24h significantly increased the expression of interleukin-6 (IL-6) and IL-8 in the skin as well as in the culture medium in proportion to the HC chain length. As the exposure time increased to 48h, IL-6 concentrations increased 2-fold compared to the IL-6 values at 24h. The in vivo skin irritation data also showed that both TEWL and erythema scores increased with increased HCs chain length (C9-C16). In conclusion, the EFT-300 showed that the skin irritation profile of HCs was in the order of C9C10C11C12

  7. Recent Progress in Electronic Skin.

    PubMed

    Wang, Xiandi; Dong, Lin; Zhang, Hanlu; Yu, Ruomeng; Pan, Caofeng; Wang, Zhong Lin

    2015-10-01

    The skin is the largest organ of the human body and can sense pressure, temperature, and other complex environmental stimuli or conditions. The mimicry of human skin's sensory ability via electronics is a topic of innovative research that could find broad applications in robotics, artificial intelligence, and human-machine interfaces, all of which promote the development of electronic skin (e-skin). To imitate tactile sensing via e-skins, flexible and stretchable pressure sensor arrays are constructed based on different transduction mechanisms and structural designs. These arrays can map pressure with high resolution and rapid response beyond that of human perception. Multi-modal force sensing, temperature, and humidity detection, as well as self-healing abilities are also exploited for multi-functional e-skins. Other recent progress in this field includes the integration with high-density flexible circuits for signal processing, the combination with wireless technology for convenient sensing and energy/data transfer, and the development of self-powered e-skins. Future opportunities lie in the fabrication of highly intelligent e-skins that can sense and respond to variations in the external environment. The rapidly increasing innovations in this area will be important to the scientific community and to the future of human life.

  8. Pain-induced skin autoimmunity.

    PubMed

    Odoardi, Francesca; Neuhuber, Winfried; Flügel, Alexander

    2014-09-01

    A recent paper published in Nature reports sensory nerve fibers in the skin that give local immune cells important instructions for the organization of an immune response; in this particular case the cooperation between the nervous and immune systems had disastrous consequences, namely an auto-destruction of the skin.

  9. TOXIC RESPONSES OF THE SKIN

    EPA Science Inventory

    The importance of fish skin is realized when one considers it is the interface between the external and intrnal environment of the animal. As will be pointed out in this chapter, fish skin has a number of vital functions many of which could be life threatening if perturbed beyond...

  10. Ingested hyaluronan moisturizes dry skin

    PubMed Central

    2014-01-01

    Hyaluronan (HA) is present in many tissues of the body and is essential to maintain moistness in the skin tissues, which contain approximately half the body’s HA mass. Due to its viscosity and moisturizing effect, HA is widely distributed as a medicine, cosmetic, food, and, recently marketed in Japan as a popular dietary supplement to promote skin moisture. In a randomized, double-blind, placebo-controlled clinical study it was found that ingested HA increased skin moisture and improved treatment outcomes for patients with dry skin. HA is also reported to be absorbed by the body distributed, in part, to the skin. Ingested HA contributes to the increased synthesis of HA and promotes cell proliferation in fibroblasts. These effects show that ingestion of HA moisturizes the skin and is expected to improve the quality of life for people who suffer from dry skin. This review examines the moisturizing effects of dry skin by ingested HA and summarizes the series of mechanisms from absorption to pharmacological action. PMID:25014997

  11. Serotoninergic system in hamster skin.

    PubMed

    Slominski, Andrzej; Pisarchik, Alexander; Semak, Igor; Sweatman, Trevor; Szczesniewski, Andre; Wortsman, Jacobo

    2002-10-01

    We have cloned the tryptophan hydroxylase cDNA from hamster pituitary and demonstrated its expression in the skin, melanotic and amelanotic melanomas, spleen, heart, and the eye. We further demonstrated that skin, melanomas, spleen, pituitary, and eye but not heart expressed arylalkylamine N-acetyltransferase mRNA. The cutaneous expression of the arylalkylamine N-acetyltransferase gene was accompanied by enzymatic activity for the conversion of serotonin and tryptamine to N-acetylserotonin and N-acetyltryptamine, respectively. There was marked regional variation in the serotonin N-acetyltransferase activity, which was higher in ear skin than in corpus skin, and was lower in melanomas than in normal skin. Serotonin N-acetyltransferase activity was significantly inhibited by Cole bisubstrate at low concentration (skin. We also documented both the in vitro transformation of serotonin to N-acetylserotonin using liquid chromatography/mass spectrometry and the generation/storage of N-acetylserotonin in cultured melanoma cells. Thus, we have uncovered a cutaneous pathway displaying capabilities for serotonin biosynthesis and/or its metabolism to N-acetylserotonin in rodent skin. As serotonin has powerful vasodilator, immunomodulator, and growth factor actions, this pathway could be involved in skin physiology and/or pathology.

  12. Aging Differences in Ethnic Skin

    PubMed Central

    Buainain De Castro Maymone, Mayra; Kundu, Roopal V.

    2016-01-01

    Aging is an inevitable and complex process that can be described clinically as features of wrinkles, sunspots, uneven skin color, and sagging skin. These cutaneous effects are influenced by both intrinsic and extrinsic factors and often are varied based on ethnic origin given underlying structural and functional differences. The authors sought to provide updated information on facets of aging and how it relates to ethnic variation given innate differences in skin structure and function. Publications describing structural and functional principles of ethnic and aging skin were primarily found through a PubMed literature search and supplemented with a review of textbook chapters. The most common signs of skin aging despite skin type are dark spots, loss of elasticity, loss of volume, and rhytides. Skin of color has many characteristics that make its aging process unique. Those of Asian, Hispanic, and African American descent have distinct facial structures. Differences in the concentration of epidermal melanin makes darkly pigmented persons more vulnerable to dyspigmentation, while a thicker and more compact dermis makes facial lines less noticeable. Ethnic skin comprises a large portion of the world population. Therefore, it is important to understand the unique structural and functional differences among ethnicities to adequately treat the signs of aging. PMID:26962390

  13. Moisturizing Different Racial Skin Types

    PubMed Central

    Wong, Victor W.; Longaker, Michael T.; Yang, George P.

    2014-01-01

    The skin is a complex organ involved in thermoregulation, gas exchange, protection against pathogens, and barrier function to maintain proper hydration. When dry, the ability for skin to execute these tasks becomes impaired. Dry skin affects almost everyone as we age, but it is also dependent on external factors, such as dry climate, colder temperatures, and repeated washing. In addition, increasing evidence has shown racial variability in the physiological properties of skin, which directly impacts water content of the stratum corneum and sensitivity to exogenously applied agents. A multitude of products have been developed to treat dry skin, and as a group, moisturizers have been designed to either impart or restore hydration in the stratum corneum. Given the large number of moisturizers presently available, depending on individual components, several different mechanisms may be employed to promote skin hydration. As there exists dramatic racial variability in skin properties, certain moisturizers may thus be more effective in some and less effective in others to treat the common condition of dry skin. PMID:25013536

  14. Skin Diseases in the Tropics.

    ERIC Educational Resources Information Center

    Mahe, Antoine; And Others

    1994-01-01

    Common skin diseases are prevalent in tropical countries because of extreme weather conditions, mediocre hygiene, and lack of adequate treatment of infectious dermatoses. This guide describes the major endemic skin diseases and their signs for the purpose of helping unspecialized health agents train themselves and determine when a patient should…

  15. Recent Progress in Electronic Skin

    PubMed Central

    Wang, Xiandi; Dong, Lin; Zhang, Hanlu; Yu, Ruomeng; Wang, Zhong Lin

    2015-01-01

    The skin is the largest organ of the human body and can sense pressure, temperature, and other complex environmental stimuli or conditions. The mimicry of human skin's sensory ability via electronics is a topic of innovative research that could find broad applications in robotics, artificial intelligence, and human–machine interfaces, all of which promote the development of electronic skin (e‐skin). To imitate tactile sensing via e‐skins, flexible and stretchable pressure sensor arrays are constructed based on different transduction mechanisms and structural designs. These arrays can map pressure with high resolution and rapid response beyond that of human perception. Multi‐modal force sensing, temperature, and humidity detection, as well as self‐healing abilities are also exploited for multi‐functional e‐skins. Other recent progress in this field includes the integration with high‐density flexible circuits for signal processing, the combination with wireless technology for convenient sensing and energy/data transfer, and the development of self‐powered e‐skins. Future opportunities lie in the fabrication of highly intelligent e‐skins that can sense and respond to variations in the external environment. The rapidly increasing innovations in this area will be important to the scientific community and to the future of human life. PMID:27980911

  16. Topical oleo-hydrogel preparation of ketoprofen with enhanced skin permeability.

    PubMed

    Rhee, G J; Woo, J S; Hwang, S J; Lee, Y W; Lee, C H

    1999-06-01

    In an attempt to improve the skin penetration of ketoprofen, various transdermal formulations were prepared, and their in vitro skin permeability and in vivo percutaneous absorption were evaluated. In vitro permeation studies were performed using a modified Franz cell diffusion system in which permeation parameters such as cumulative amount at 8 hr Q8hr, steady-state flux Jss, or lag time tL were determined. In the in vivo percutaneous absorption study using the hairless mouse, maximum concentration Cmax and area under the curve at 24 hr AUC24h were measured. The optimal transdermal formulation (oleo-hydrogel formulation) of ketoprofen showed a Q8hr value of 227.20 micrograms/cm2, a Jss value of 29.61 micrograms/cm2/hr, and a tL value of 0.46 hr. The Q8hr and Jss values were about 10-fold (p < .01) higher than those (Q8hr = 19.61 micrograms/cm2; Jss = 2.66 micrograms/cm2/hr) from the K-gel and about 3.5-fold (p < .01) than those (Q8hr = 60.00 micrograms/cm2; Jss = 7.99 micrograms/cm2/hr) of the K-plaster. In the in vivo percutaneous absorption, the Cmax (6.82 micrograms/ml) and AUC24h (55.74 micrograms.hr/ml) values of the optimal formulation were significantly (p < .01) higher than those of K-gel and K-plaster. The relative bioavailability of the oleo-hydrogel following transdermal administration in reference to oral administration was about 37%, and the Cmax value (4.73 micrograms/cm2) in the hypodermis following topical administration was much higher than those from the conventional products (Cmax of K-gel and K-plaster were 0.92 +/- 0.19 microgram/cm2 and 1.27 +/- 0.37 microgram/cm2, respectively). These data demonstrate that the oleo-hydrogel formulation of ketoprofen was more beneficial than conventional products (K-gel and K-plaster) in enhancing transdermal permeation and skin absorption of ketoprofen. Furthermore, there was a good correlation between in vitro permeation parameters and in vivo percutaneous absorption parameters.

  17. [Early diagnosis of skin cancer].

    PubMed

    Kolm, Isabell; Hofbauer, Günther; Braun, Ralph P

    2010-09-01

    The skin is the most affected organ by cancer. The incidence rates of skin cancer are steadily increasing, both for melanoma and non-melanoma skin cancers (squamous cell carcinoma, basal cell carcinoma). Over 90 % of the death cases from skin cancers attribute to melanoma. Survival from melanoma is strongly related to tumour thickness. Therefore early detection is the most important step to improve prognosis. In the last years a number of new non invasive techniques for the early diagnosis of melanoma have been developed which are superior to the naked eye examination. In this overview article we present some non-invasive diagnostic techniques like total body photography, digital dermoscopy and confocal microscopy which in addition to dermoscopy assist the dermatologist in differentiating nevi from early melanomas.Non-melanoma skin cancer can be prevented by accurate sun protection. Early squamous cell carcinomas and basal cell carcinomas can be treated either invasively or non-invasively with excellent prognosis.

  18. Sensitive skin: mechanisms and diagnosis.

    PubMed

    Primavera, G; Berardesca, E

    2005-02-01

    Sensitive skin is a condition of subjective cutaneous hyperreactivity to environmental factors. Subjects experiencing this condition report exaggerated reactions when their skin is in contact with cosmetics, soaps and sunscreens, and they often report worsening after exposure to dry and cold climate. Although no sign of irritation is commonly detected, itching, burning, stinging and a tight sensation are constantly present. Generally substances that are not commonly considered irritants are involved in this abnormal response. They include many ingredients of cosmetics such as: dimethyl sulfoxide, benzoyl peroxide preparations, salicylic acid, propylene glycol, amyldimethylaminobenzoic acid and 2-ethoxyethyl methoxycinnamate. Sensitive skin and subjective irritation are widespread but still far from being completely defined and understood. The aim of this paper is to summarize the relevant literature in order to elucidate the underlying mechanisms of sensitive skin and the best testing methodologies for investigation of sensitive skin.

  19. Conservative procedures in skin reconstitution

    PubMed Central

    Wollina, Uwe

    2005-01-01

    Skin exerts a number of essential protective functions ensuring homeostasis of the whole body. In the present review barrier function of skin and its expression of antimicrobial peptides are discussed. Barrier function is provided by the dynamic stratum corneum structure composed of lipids and corneocytes. Stratum corneum is a conditio sine qua non for terrestrial life. Impairment of barrier function can be due to injury and inflammatory skin diseases. Therapeutic options are discussed with special emphasis of radiodermatitis and irritant contact dermatitis in patients with hearing device. The use of antimicrobial peptides is illustrated by facial inflammatory skin diseases. In wound healing new developments include biotechnological developments of matrix- and growth factors and tissue-engineered skin substitutes. In everyday wound care of chronic wounds the concept of wound bed preparation (TIME) constitutes the base of successful treatment. PMID:22073065

  20. Non-thermic skin affections.

    PubMed

    Broz, L; Kripner, J

    2000-01-01

    The Centre for Burns can help by its means (material, technical and personal) in the treatment of burns with extensive and deep losses of the skin cover and other tissue structures and in some affections with a different etiology (non-thermic affections). Indicated for admission are, in particular, extensive exfoliative affections--Stevens-Johnson's syndrome (SJS), Lyell's syndrome--toxic epidermal necrolysis (TEN) and staphylococcal scalded skin syndrome (SSSS), deep skin and tissue affections associated with fulminant purpura (PF), possibly other affections (epidermolysis bullosa, posttraumatic avulsions etc.). The similarity with burn injuries with loss of the skin cover grade II is typical, in particular in exfoliative affections with a need for adequate fluid replacement in the acute stage and aseptic surgical treatment of the affected area from the onset of the disease. In conditions leading to full thickness skin loss, in addition to general treatment rapid plastic surgical interventions dominate.

  1. Matching the skin barrier to the skin type.

    PubMed

    Thompson, Hyacinth; North, Jacqui; Davenport, Rebecca; Williams, Julia

    Peristomal skin problems are thought to be common (Herlufsson et al, 2006; Williams et al, 2010), and can interfere with the security of stoma products. Stoma patients are reliant on the integrity of their peristomal skin to maintain a normal lifestyle. Bekkers et al (1996) highlighted that, if the peristomal skin becomes damaged, it not only affects the person physically, but also psychologically, ultimately prolonging rehabilitation and adaptation to the stoma. Therefore, it can be concluded that maintaining skin integrity is a basic and essential skill in ensuring good stoma management. This article explores the assessment of four stoma patients, highlighting the importance of matching their skin type with their skin barrier for optimum skin protection. The patients have kindly agreed for their case studies to be published as a means of informing others. All names have been changed in line with Nursing and Midwifery Council (2010) guidelines to maintain patient confidentiality. This article was originally presented at the World Council of Enterostomal Therapists' (WCET) annual conference in 2010, receiving first prize at poster presentations.

  2. Skin protection in the prevention of skin diseases.

    PubMed

    Elsner, Peter

    2007-01-01

    Occupational skin diseases comprise a wide spectrum of conditions. Under epidemiological aspects, occupational contact dermatitis that is usually manifested on the hands is the most frequent occupational skin disease with an estimated average incidence rate of 0.7-1.5 cases per 1,000 workers per year. Irritant dermatitis is due to individual susceptibility and the exposure to irritants such as wet work combined with detergents or other hydrophilic irritants or solvents at the workplace. Chronic irritant dermatitis is a risk factor for delayed-type sensitization and subsequently allergic contact dermatitis. It is therefore the prevention of chronic or cumulative irritant dermatitis that is the decisive factor in the prevention of occupational skin disease. Within prevention programs at the workplace, skin protection plays an important, but limited role. Others are technical and organizational means to avoid or reduce skin exposure to irritants and allergens. Educational measures to increase the awareness of workers for workplace hazards and to motivate them to use skin protection measures appropriately are just as important as the careful selection of skin protection materials.

  3. 75 FR 52755 - Draft Guidance for Industry on Acute Bacterial Skin and Skin Structure Infections: Developing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-27

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Acute Bacterial Skin and Skin... guidance for industry entitled ``Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for... the development of antimicrobial drugs for the treatment of acute bacterial skin and skin...

  4. α-Santalol, a skin cancer chemopreventive agent with potential to target various pathways involved in photocarcinogenesis.

    PubMed

    Santha, Sreevidya; Dwivedi, Chandradhar

    2013-01-01

    This study is designed to investigate the chemopreventive effect and molecular mechanisms of α-santalol on UVB-induced skin tumor development in SKH-1 hairless mouse, a widely used model for human photocarcinogenesis. A dose of UVB radiation (30 mJ cm(-2) day(-1)) that is in the range of human sunlight exposure was used for the initiation and promotion of tumor. Topical treatment of mice with α-santalol (10%, wt/vol in acetone) caused reduction in tumor incidence, multiplicity and volume. In our study, the anticarcinogenic action of α-santalol against UVB-induced photocarcinogenesis was found to be associated with inhibition of inflammation and epidermal cell proliferation, cell cycle arrest and induction of apoptosis. α-Santalol pretreatment strongly inhibited UVB-induced epidermal hyperplasia and thickness of the epidermis, expression of proliferation and inflammation markers proliferating cell nuclear antigen (PCNA), Ki-67 and cyclooxygenase 2 (Cox-2). Significant decrease in the expression of cyclins A, B1, D1 and D2 and cyclin-dependent kinases (Cdk)s Cdk1 (Cdc2), Cdk2, Cdk4 and Cdk6 and an upregulated expression of cyclin-dependent kinase (CDK) inhibitor Cip1/p21 were found in α-santalol pretreated group. Furthermore, an elevated level of cleaved caspase 3 and cleaved poly (ADP-ribose) polymerase (PARP) were observed in α-santalol-treated group. Our data suggested that α-santalol is a safer and promising skin cancer chemopreventive agent with potential to target various pathways involved in photocarcinogenesis.

  5. Response of mouse skin to tattooing: use of SKH-1 mice as a surrogate model for human tattooing

    SciTech Connect

    Gopee, Neera V.; Cui, Yanyan; Olson, Greg; Warbritton, Alan R.; Miller, Barbara J.; Couch, Letha H.; Wamer, Wayne G.; Howard, Paul C. . E-mail: PHoward@nctr.fda.gov

    2005-12-01

    Tattooing is a popular cosmetic practice involving more than 45 million US citizens. Since the toxicology of tattoo inks and pigments used to formulate tattoo inks has not been reported, we studied the immunological impact of tattooing and determined recovery time from this trauma. SKH-1 hairless mice were tattooed using commercial tattoo inks or suspensions of titanium dioxide, cadmium sulfide, or iron oxide, and sacrificed at 0.5, 1, 3, 4, 7, or 14 days post-tattooing. Histological evaluation revealed dermal hemorrhage at 0.5 and 1 day. Acute inflammation and epidermal necrosis were initiated at 0.5 day decreasing in incidence by day 14. Dermal necrosis and epidermal hyperplasia were prominent by day 3, reducing in severity by day 14. Chronic active inflammation persisted in all tattooed mice from day 3 to 14 post-tattooing. Inguinal and axillary lymph nodes were pigmented, the inguinal being most reactive as evidenced by lymphoid hyperplasia and polymorphonuclear infiltration. Cutaneous nuclear protein concentrations of nuclear factor-kappa B were elevated between 0.5 and 4 days. Inflammatory and proliferative biomarkers, cyclooxygenase-1, cyclooxygenase-2, and ornithine decarboxylase protein levels were elevated between 0.5 and 4 days in the skin and decreased to control levels by day 14. Interleukin-1 beta and interleukin-10 were elevated in the lymph nodes but suppressed in the tattooed skin, with maximal suppression occurring between days 0.5 and 4. These data demonstrate that mice substantially recover from the tattooing insult by 14 days, leaving behind pigment in the dermis and the regional lymph nodes. The response seen in mice is similar to acute injury seen in humans, suggesting that the murine model might be a suitable surrogate for investigating the toxicological and phototoxicological properties of ingredients used in tattooing.

  6. Treatment Options for Nonmelanoma Skin Cancer

    MedlinePlus

    ... Skin Cancer Skin color and being exposed to sunlight can increase the risk of nonmelanoma skin cancer ... carcinoma include the following: Being exposed to natural sunlight or artificial sunlight (such as from tanning beds) ...

  7. Male skin and ingredients relevant to male skin care.

    PubMed

    Draelos, Z D

    2012-03-01

    Male skin care needs are heavily influenced by the need to remove facial hair on a regular basis. Facial skin issues associated with poor hair removal approaches are common and include razor burn and irritation. This paper evaluates current research on shaving technology and how careful ingredient selection can contribute to male skin health. The importance of maintaining hair softness during the shave and restoring facial hydration post-shave is discussed. Data are presented on how post-shave moisturizers containing glycerine and emollients can create an environment for improved barrier function which can be further improved by incorporating specific ingredients such as niacinamide.

  8. Conditioning in laser skin resurfacing - betulin emulsion and skin recovery.

    PubMed

    Metelmann, Hans-Robert; Podmelle, Fred; Waite, Peter D; Müller-Debus, Charlotte Friederieke; Hammes, Stefan; Funk, Wolfgang

    2013-04-01

    Laser skin resurfacing of the face by CO₂-laser ablation is causing superficial wounds that need rapid recovery to reduce the risk of infection, the risk of chronification and as a result the risk of unaesthetic scars. The question being addressed by this study is to demonstrate benefit of betulin emulsion skin care after CO₂-laser wounds. The outcome of this aesthetic comparison between betulin emulsion, moist wound dressing and gauze covering in promoting the recovery process in laser skin ablation is to demonstrate improved aesthetic benefit for the patient.

  9. Skin hygiene practices, emollient therapy and skin vulnerability.

    PubMed

    Voegeli, David

    The promotion and maintenance of skin integrity is one of the most common challenges for nurses in every sphere of practice, but particularly for those caring for patients with chronic inflammation of the skin (such as in eczema and psoriasis), and to those at risk of skin breakdown due to immobility, circulatory disease, or incontinence. A significant amount of nursing time is spent washing patients, or assisting them to wash. However, little attention has been given to a scientific appraisal or evidence of the effectiveness of these activities.

  10. Ultraviolet Light and Skin Cancer in Athletes

    PubMed Central

    Harrison, Shannon C.; Bergfeld, Wilma F.

    2009-01-01

    The incidence of melanoma and nonmelanoma skin cancers is increasing worldwide. Ultraviolet light exposure is the most important risk factor for cutaneous melanoma and nonmelanoma skin cancers. Nonmelanoma skin cancer includes basal cell carcinoma and squamous cell carcinoma. Constitutive skin color and genetic factors, as well as immunological factors, play a role in the development of skin cancer. Ultraviolet light also causes sunburn and photoaging damage to the skin. PMID:23015891

  11. Leukotrienes orchestrating allergic skin inflammation.

    PubMed

    Sadik, Christian D; Sezin, Tanya; Kim, Nancy D

    2013-11-01

    Leukotrienes constitute a group of lipid mediators, which may be subdivided into two groups, with leukotriene B4 on the one hand and cysteinyl leukotrienes on the other. Although leukotrienes are abundantly expressed in skin affected by diverse chronic inflammatory diseases, including atopic dermatitis, psoriasis, pemphigus vulgaris and bullous pemphigoid, their pathological roles in these diseases have remained elusive. Recent data now reveal that both leukotriene B4 and cysteinyl leukotrienes are indispensable in the pathogenesis of atopic dermatitis, with leukotriene B4 initiating the recruitment of inflammatory cells, particularly neutrophils and TH 2 cells into the skin, and cysteinyl leukotrienes later inducing characteristic structural alterations of chronically affected skin, specifically skin fibrosis and keratinocyte proliferation. Thus, these results reveal a sequential cooperation of LTB4 and cysteinyl leukotrienes to initiate and perpetuate allergic skin inflammation. These new insights highlight leukotrienes as promising therapeutic targets in allergic skin inflammation and should encourage more research into the role of leukotrienes in other inflammatory skin diseases.

  12. Skin and hair changes during pregnancy

    MedlinePlus

    ... pregnancy; Polymorphic eruption of pregnancy; Melasma - pregnancy; Prenatal skin changes ... during pregnancy may have other effects on your skin. Some women get brownish or yellowish patches around ...

  13. Filaggrin and Skin Barrier Function.

    PubMed

    Kezic, Sanja; Jakasa, Ivone

    2016-01-01

    The skin barrier function is greatly dependent on the structure and composition of the uppermost layer of the epidermis, the stratum corneum (SC), which is made up of flattened anucleated cells surrounded by highly organized and continuous lipid matrix. The interior of the corneocytes consists mainly of keratin filaments aggregated by filaggrin (FLG) protein. Next, together with several other proteins, FLG is cross-linked into a mechanically robust cornified cell envelope providing a scaffold for the extracellular lipid matrix. In addition to its role for the SC structural and mechanical integrity, FLG degradation products account in part for the water-holding capacity and maintenance of acidic pH of the SC, both crucial for the epidermal barrier homoeostasis by regulating activity of multiple enzymes that control desquamation, lipid synthesis and inflammation. The major determinant of FLG expression in the skin are loss-of-function mutations in FLG, the strongest genetic risk factor for atopic dermatitis (AD), an inflammatory skin disease characterized by a reduced skin barrier function. The prevalence of FLG mutations varies greatly among different populations and ranges from about 10% in Northern Europeans to less than 1% in the African populations. An impaired skin barrier facilitates absorption of potentially hazardous chemicals, which might cause adverse effects in the skin, such as contact dermatitis, or systemic toxicity after their passage into blood. In another direction, a leaky epidermal barrier will lead to enhanced loss of water from the skin. A recent study has shown that even subtle increase in epidermal water loss in newborns increases the risk for AD. Although there are multiple modes of action by which FLG might affect skin barrier it is still unclear whether and how FLG deficiency leads to the reduced skin barrier function. This chapter summarizes the current knowledge in this field obtained from clinical studies, and animal and in vitro models

  14. Lyme Borreliosis and Skin

    PubMed Central

    Vasudevan, Biju; Chatterjee, Manas

    2013-01-01

    Lyme disease is a multisystem illness which is caused by the strains of spirochete Borrelia burgdorferi sensu lato and transmitted by the tick, Ixodes. Though very commonly reported from the temperate regions of the world, the incidence has increased worldwide due to increasing travel and changing habitats of the vector. Few cases have been reported from the Indian subcontinent too. Skin manifestations are the earliest to occur, and diagnosing these lesions followed by appropriate treatment, can prevent complications of the disease, which are mainly neurological. The three main dermatological manifestations are erythema chronicum migrans, borrelial lymphocytoma and acrodermatitis chronica atrophicans. Many other dermatological conditions including morphea, lichen sclerosus and lately B cell lymphoma, have been attributed to the disease. Immunofluorescence and polymerase reaction tests have been developed to overcome the problems for diagnosis. Culture methods are also used for diagnosis. Treatment with Doxycycline is the mainstay of management, though prevention is of utmost importance. Vaccines against the condition are still not very successful. Hence, the importance of recognising the cutaneous manifestations early, to prevent systemic complications which can occur if left untreated, can be understood. This review highlights the cutaneous manifestations of Lyme borreliosis and its management. PMID:23723463

  15. Skin-sparing mastectomy

    PubMed Central

    Rancati, Alberto O.

    2015-01-01

    The surgical treatment of breast cancer has evolved rapidly in recent decades. Conservative treatment was adopted in the late 1970s, with rates above 70%, and this was followed by a period during which the indications for surgical intervention were expanded to those patients at high risk for BRCA1, BRCA2 mutations, and also due to new staging standards and use of nuclear magnetic resonance. This increase in the indications for mastectomy coincided with the availability of immediate breast reconstruction as an oncologically safe and important surgical procedure for prevention of sequelae. Immediate reconstruction was first aimed at correcting the consequences of treatment, and almost immediately, the challenge of the technique became the achievement of a satisfactory breast appearance and shape, as well as normal consistency. The skin-sparing mastectomy (SSM) in conservation first and nipple-areola complex (NAC) later was a result of this shift that occurred from the early 1990s to the present. The objective of this review is to present all these developments specifically in relation to SSM and analyze our personal experience as well as the experience of surgeons worldwide with an emphasis on the fundamental aspects, indications, surgical technique, complications, oncological safety, and cosmetic results of this procedure. PMID:26645008

  16. Development of prosthetic skin

    NASA Astrophysics Data System (ADS)

    Kilaru, Rohit

    The objective of this research was to embed tactile sensors in polyimides. This novel method could be utilized to realize prosthetic skin for sensing different kinds of mechanical stimuli. Tactile sensors have an increasing demand in medical sectors: upper and lower-limb prosthetics and in the industrial sectors: robot end-effectors, grippers and manipulators. The sensors developed are targeted for prosthetic arm tactile sensing applications. Current work presents piezoresistive differential pressure sensors fabricated on flexible polyimide film or substrate. A unique technique to bond a flexible superstrate polyimide layer to a MEMS tactile sensor array is presented in this thesis. The sensor is made of aluminium oxide membrane layer with nichrome piezoresistors as the half-Wheatstone bridge elements. Four different types of sensor designs have been characterized to obtain gauge factor of thin film nichrome. The sensor arrays with and without the superstrate film were simulated for obtaining the maximum stress, average strain and deflection of the membrane. The maximum change in output voltage was 0.8 mV. The gauge factors calculated for tactile sensor with superstrate range between 2.2 to 7.8 and without superstrate range 1.5 to 5.7.

  17. Skin fungal biocontamination and the skin hydrogel pad test.

    PubMed

    Paquet, P; Piérard-Franchimont, C; Piérard, G E; Quatresooz, P

    2008-04-01

    Previous observations have revealed that environmental nondermatophyte molds (NDM) can grow inside specific hydrogel pads (LaserAid). Some of these NDM might be responsible for superficial and invasive mycoses as well as for allergic respiratory and cutaneous disorders. The load of NDM propagules in the environment is considered to be an important risk factor for all these diseases. It is postulated that the quantification of the responsible fungi deposited at the skin surface may be an indicator of a recent exposure to environmental fungi. The aim of the present study was to assess using the LaserAid hydrogel pads, the density of living NDM adhering to the skin surface of healthy subjects. Sterile hydrogel pads were applied in a repeat procedure onto the normal-looking skin of the palms and face of 35 healthcare workers who were active in low exposure areas. Similar samplings were performed after washing the skin with a regular skin cleanser, or after applying an alcohol solution or a povidone iodine solution. As controls, 20 sterile pads were exposed for a few minutes to ambient air of the laboratory without any contact with the skin. Each of these samples was stored for 2 weeks at room temperature in a clean protected environment. After that period, visual inspection of the pads was followed by microscopic examination of PAS-stained 6 microm-thick sections. In addition, mycological cultures were performed from pieces of the pads deposited onto Sabouraud agar plates. While 19/20 air-exposed samples were not contaminated by environmental air-borne fungi, 61/70 of the initial skin samplings and 6/70 of the repeat skin samplings showed foci of fungal colonization confirmed by microscopic examination. No specific differences were disclosed between the face and palm samplings. Cultures revealed the presence of NDM in the majority (64/67) of the colonized pads, and a few Candida albicans contaminations (3/67) were also disclosed. The cleansing with a non

  18. Dermoscopy of pigmented skin lesions.

    PubMed

    Soyer, H P; Argenziano, G; Chimenti, S; Ruocco, V

    2001-01-01

    This paper describes the basic concepts of dermoscopy, the various dermoscopic equipments and the standard criteria for diagnosing pigmented skin lesions. In assessing dermoscopic images, both global and local features can be recognized. These features will be systematically described and illustrated in Part I of this article. First, we will focus on 8 morphologically rather distinctive global features that allow a quick, preliminary categorization of a given pigmented skin lesion. Second, we will describe various local features representing the letters of the dermoscopic alphabet. The local features permit a more detailed assessment of pigmented skin lesions.

  19. [Skin signs in child abuse].

    PubMed

    Pau-Charles, I; Darwich-Soliva, E; Grimalt, R

    2012-03-01

    Child abuse is far more prevalent today than is generally recognized. Up to 90% of victims suffer physical abuse that can be observed in signs on the skin. Dermatologists are particularly qualified to identify these signs and distinguish them from other conditions that can mimic abuse. This review covers the signs of child abuse that can be observed on the skin. We discuss clues that can help differentiate between lesions caused by abuse and those that are accidental, and we describe the skin conditions that mimic physical abuse.

  20. [Non-irritating skin protector].

    PubMed

    Gago Fornells, Manuel; García González, R Fernando; Gaztelu Valdés, Victoriana

    2002-05-01

    In this article, the authors describe the multiple uses a non irritating cutaneous protector has as an effective tool against the aggressions which peri-lesion skin and other at risk skins suffer when they are subject to constant and direct contact with secretions and liquids resulting from the use of dressings based on wet cures, or systems of continence related to ostomias, or in those patients who suffer mixed incontinence where diaper rash makes it difficult to maintain and care for the skin.