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Sample records for 12-o-tetradecanoylphorbol-13-acetate-treated mouse skin

  1. Hemin inhibits cyclooxygenase-2 expression through nuclear factor-kappa B activation and ornithine decarboxylase expression in 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin

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    Park, Jae Hee; Lee, Chang Ki [Department of Oral Biology, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Oral Cancer Research Institute, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Hwang, Young Sun [Department of Applied Life Science and Brain Korea 21 Project, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Park, Kwang-Kyun [Department of Oral Biology, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Department of Applied Life Science and Brain Korea 21 Project, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Chung, Won-Yoon [Department of Oral Biology, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of); Department of Applied Life Science and Brain Korea 21 Project, Yonsei University College of Dentistry, 134 Shinchon-Dong, Seodaemoon-Ku, Seoul 120-752 (Korea, Republic of)], E-mail: wychung@yuhs.ac

    2008-07-03

    Inflammation induced by various stimuli has been found to be associated with increased risk for most types of human cancer. Inflammation facilitates the initiation of normal cells, as well as the growth of initiated cells and their progression to malignancy through production of proinflammatory cytokines and diverse reactive oxygen/nitrogen species. These also activate the signaling molecules that are involved in inflammation and carcinogenesis. Our previous studies have demonstrated that hemin inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced bacterial mutagenesis and oxidative DNA damage, reduced the level of DNA-DMBA adduct and 12-O-tetradecanoylphorobl-13-acetate (TPA)-induced tumor formation in DMBA-initiated ICR mouse skin, and inhibited myeloperoxidase and ornithine decarboxylase (ODC) activity and H{sub 2}O{sub 2} formation in TPA-treated mouse skin. In the present study, to further elucidate the molecular mechanisms underlying the chemopreventive activity of hemin, its effect on the expression of ODC and cyclooxygenase (COX)-2, and the activation of nuclear factor-kappa B (NF-{kappa}B) and mitogen-activated protein kinases (MAPKs) regulating these proteins were explored in mouse skin with TPA-induced inflammation. Topically applied hemin inhibited ear edema and epidermal thickness in mice treated with TPA. Pretreatment with hemin reduced the expression of ODC and COX-2, and also reduced NF-{kappa}B activation in TPA-stimulated mouse skin. In addition, hemin suppressed the TPA-induced activation of extracellular signal-regulated protein kinase (ERK) and p38 MAPK in a dose-dependent manner. Taken together, hemin inhibited TPA-induced COX-2 expression by altering NF-{kappa}B signaling pathway via ERK and p38 MAPK, as well as TPA-induced ODC expression in mouse skin. Thereby, hemin may be an attractive candidate for a chemopreventive agent.

  2. Erucin Exerts Anti-Inflammatory Properties in Murine Macrophages and Mouse Skin: Possible Mediation through the Inhibition of NFκB Signaling

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    Ki Won Lee

    2013-10-01

    Full Text Available Erucin, an isothiocyanate, is a hydrolysis product of glucoerucin found in arugula and has recently been reported to have anti-cancer properties in various cancer cells. In this study, we assessed the anti-inflammatory effects of erucin and the underlying mechanisms, using lipopolysaccharide (LPS-stimulated RAW 264.7 murine macrophages and 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin. In RAW 264.7 cells, erucin (2.5, 5 μmol/L inhibited LPS-induced production of nitric oxide and prostaglandin E2. Erucin inhibited LPS-induced degradation of the inhibitor of κBα and translocation of p65 to the nucleus and, subsequently, reduced LPS-induced nuclear factor κB (NFκB DNA binding activities, as well as the transcriptional activity of NFκB, leading to the decreased expression of NFκB-target genes, including tumor necrosis factor-α, interleukin (IL-6, IL-1β, inducible nitric oxide synthase (iNOS and cyclooxygenase (COX-2, as well as transcriptional activity of iNOS and COX-2. In mice, erucin (100, 300 nmoles treatment significantly inhibited phorbol ester-induced formation of ear edema and expression of iNOS and COX-2 proteins. These results indicate that erucin exerts a potent anti-inflammatory activity by inhibiting the pro-inflammatory enzymes and cytokines, which may be mediated, at least in part, via the inhibition of NFκB signaling.

  3. Erucin exerts anti-inflammatory properties in murine macrophages and mouse skin: possible mediation through the inhibition of NFκB signaling.

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    Cho, Han Jin; Lee, Ki Won; Park, Jung Han Yoon

    2013-10-15

    Erucin, an isothiocyanate, is a hydrolysis product of glucoerucin found in arugula and has recently been reported to have anti-cancer properties in various cancer cells. In this study, we assessed the anti-inflammatory effects of erucin and the underlying mechanisms, using lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages and 12-O-tetradecanoylphorbol-13-acetate-treated mouse skin. In RAW 264.7 cells, erucin (2.5, 5 μmol/L) inhibited LPS-induced production of nitric oxide and prostaglandin E2. Erucin inhibited LPS-induced degradation of the inhibitor of κBα and translocation of p65 to the nucleus and, subsequently, reduced LPS-induced nuclear factor κB (NFκB) DNA binding activities, as well as the transcriptional activity of NFκB, leading to the decreased expression of NFκB-target genes, including tumor necrosis factor-α, interleukin (IL)-6, IL-1β, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, as well as transcriptional activity of iNOS and COX-2. In mice, erucin (100, 300 nmoles) treatment significantly inhibited phorbol ester-induced formation of ear edema and expression of iNOS and COX-2 proteins. These results indicate that erucin exerts a potent anti-inflammatory activity by inhibiting the pro-inflammatory enzymes and cytokines, which may be mediated, at least in part, via the inhibition of NFκB signaling.

  4. Biological characteristics of mouse skin melanocytes.

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    Shi, Zhanquan; Ji, Kaiyuan; Yang, Shanshan; Zhang, Junzhen; Yao, Jianbo; Dong, Changsheng; Fan, Ruiwen

    2016-04-01

    The objective of this research was to evaluate the optimal passage number according to the biological characteristics of mouse skin melanocytes from different passages. Skin punch biopsies harvested from the dorsal region of 2-day old mice were used to establish melanocyte cultures. The cells from passage 4, 7, 10 and 13 were collected and evaluated for their melanogenic activity. Histochemical staining for tyrosinase (TYR) activity and immunostaining for the melanocyte specific markers including S-100 antigen, TYR, tyrosinase related protein 1 (TYRP1), tyrosinase related protein 2 (TYRP2) and micropthalmia associated transcription factor (MITF) confirmed purity and melanogenic capacity of melanocytes from different passages, with better melanogenic activity of passage 10 and 13 cells being observed. Treatment of passage 13 melanocytes with α-melanocyte stimulating hormone (α-MSH) showed increased expression of MITF, TYR and TYRP2 mRNA. However, considering the TYR mRNA dramatically high expression which is the characteristics of melanoma cells, melanocytes from passage 10 was the optimal passage number for the further research. Our results demonstrate culture of pure populations of mouse melanocytes to at least 10 passages and illustrate the potential utility of passage 10 cells for studies of intrinsic and extrinsic regulation of genes controlling pigmentation and coat color in mouse.

  5. Multistage chemical carcinogenesis in mouse skin

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    Slaga, T.J.; Fischer, S.M.; Weeks, C.E.; Klein-Szanto, A.J.P.

    1979-01-01

    Skin tumors in mice can be induced by the sequential application of a subthreshold dose of a carcinogen (initiation phase) followed by repetitive treatment with a noncarcinogenic tumor promoter. The initiation phase requires only a single application of either a direct acting carcinogen or a procarcinogen which has to be metabolized before being active and is essentially an irreversible step which probably involves a somatic cell mutation. There is a good correlation between the skin tumor initiating activites of several polycyclic aromatic hydrocarbons (PAH) and their ability to bind covalently to epidermal DNA. Laboratory results suggest that bay region diol-epoxides are the ultimate carcinogenic form of PAH carcinogens. Potent inhibitors and stimulators of PAH tumor initiation appear to affect the level of the PAH diol-epoxide reacting with specific DNA bases. Reecent data suggests that the tumor promotion stage involves at least three important steps: (1) the induction of embryonic looking cells (dark cells) in adult epidermis; (2) an increased production of epidermal prostaglandins and polyamines; (3) sustained proliferation of dark cells. Retinoic acid specifically inhibits step two whereas the anti-inflammatory steriod fluocinolone acetonide is a potent inhibitor of steps one and three. The mechanism and the importance of a specific sequence for each step in chemical carcinogenesis in mouse skin are detailed.

  6. The top skin-associated genes: a comparative analysis of human and mouse skin transcriptomes.

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    Gerber, Peter Arne; Buhren, Bettina Alexandra; Schrumpf, Holger; Homey, Bernhard; Zlotnik, Albert; Hevezi, Peter

    2014-06-01

    The mouse represents a key model system for the study of the physiology and biochemistry of skin. Comparison of skin between mouse and human is critical for interpretation and application of data from mouse experiments to human disease. Here, we review the current knowledge on structure and immunology of mouse and human skin. Moreover, we present a systematic comparison of human and mouse skin transcriptomes. To this end, we have recently used a genome-wide database of human gene expression to identify genes highly expressed in skin, with no, or limited expression elsewhere - human skin-associated genes (hSAGs). Analysis of our set of hSAGs allowed us to generate a comprehensive molecular characterization of healthy human skin. Here, we used a similar database to generate a list of mouse skin-associated genes (mSAGs). A comparative analysis between the top human (n=666) and mouse (n=873) skin-associated genes (SAGs) revealed a total of only 30.2% identity between the two lists. The majority of shared genes encode proteins that participate in structural and barrier functions. Analysis of the top functional annotation terms revealed an overlap for morphogenesis, cell adhesion, structure, and signal transduction. The results of this analysis, discussed in the context of published data, illustrate the diversity between the molecular make up of skin of both species and grants a probable explanation, why results generated in murine in vivo models often fail to translate into the human.

  7. Hyperelastic Material Properties of Mouse Skin under Compression.

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    Yuxiang Wang

    Full Text Available The skin is a dynamic organ whose complex material properties are capable of withstanding continuous mechanical stress while accommodating insults and organism growth. Moreover, synchronized hair cycles, comprising waves of hair growth, regression and rest, are accompanied by dramatic fluctuations in skin thickness in mice. Whether such structural changes alter skin mechanics is unknown. Mouse models are extensively used to study skin biology and pathophysiology, including aging, UV-induced skin damage and somatosensory signaling. As the skin serves a pivotal role in the transfer function from sensory stimuli to neuronal signaling, we sought to define the mechanical properties of mouse skin over a range of normal physiological states. Skin thickness, stiffness and modulus were quantitatively surveyed in adult, female mice (Mus musculus. These measures were analyzed under uniaxial compression, which is relevant for touch reception and compression injuries, rather than tension, which is typically used to analyze skin mechanics. Compression tests were performed with 105 full-thickness, freshly isolated specimens from the hairy skin of the hind limb. Physiological variables included body weight, hair-cycle stage, maturity level, skin site and individual animal differences. Skin thickness and stiffness were dominated by hair-cycle stage at young (6-10 weeks and intermediate (13-19 weeks adult ages but by body weight in mature mice (26-34 weeks. Interestingly, stiffness varied inversely with thickness so that hyperelastic modulus was consistent across hair-cycle stages and body weights. By contrast, the mechanics of hairy skin differs markedly with anatomical location. In particular, skin containing fascial structures such as nerves and blood vessels showed significantly greater modulus than adjacent sites. Collectively, this systematic survey indicates that, although its structure changes dramatically throughout adult life, mouse skin at a given

  8. Metabolism of skin-absorbed resveratrol into its glucuronized form in mouse skin.

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    Murakami, Itsuo; Chaleckis, Romanas; Pluskal, Tomáš; Ito, Ken; Hori, Kousuke; Ebe, Masahiro; Yanagida, Mitsuhiro; Kondoh, Hiroshi

    2014-01-01

    Resveratrol (RESV) is a plant polyphenol, which is thought to have beneficial metabolic effects in laboratory animals as well as in humans. Following oral administration, RESV is immediately catabolized, resulting in low bioavailability. This study compared RESV metabolites and their tissue distribution after oral uptake and skin absorption. Metabolomic analysis of various mouse tissues revealed that RESV can be absorbed and metabolized through skin. We detected sulfated and glucuronidated RESV metabolites, as well as dihydroresveratrol. These metabolites are thought to have lower pharmacological activity than RESV. Similar quantities of most RESV metabolites were observed 4 h after oral or skin administration, except that glucuronidated RESV metabolites were more abundant in skin after topical RESV application than after oral administration. This result is consistent with our finding of glucuronidated RESV metabolites in cultured skin cells. RESV applied to mouse ears significantly suppressed inflammation in the TPA inflammation model. The skin absorption route could be a complementary, potent way to achieve therapeutic effects with RESV.

  9. Calcium Glucarate Prevents Tumor Formation in Mouse Skin

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective Calcium Glucarate (Cag), Ca salt of D-glucaric acid is a naturally occurring non-toxic compound present in fruits, vegetables and seeds of some plants, and suppress tumor growth in different models. Due to lack of knowledge about its mode of action its uses are limited in cancer chemotherapy thus the objective of the study was to study the mechanism of action of Cag on mouse skin tumorigenesis. Methods We have estimated effect of Cag on DMBA induced mouse skin tumor development following complete carcinogenesis protocol. We measured, epidermal transglutaminase activity (TG), a marker of cell differentiation after DMBA and/or Cag treatment and [3H] thymidine incorporation into DNA as a marker for cell proliferation. Results Topical application of Cag suppressed the DMBA induced mouse skin tumor development. Topical application of Cag significantly modifies the critical events of proliferation and differentiation TG activity was found to be reduced after DMBA treatment. Reduction of the TG activity was dependent on the dose of DMBA and duration of DMBA exposure. Topical application of Cag significantly alleviated DMBA induced inhibition of TG. DMBA also caused stimulation of DNA synthesis in epidermis, which was inhibited by Cag. Conclusion Cag inhibits DMBA induced mouse skin tumor development. Since stimulation of DNA synthesis reflects proliferation and induction of TG represents differentiation, the antitumorigenic effect of Cag is considered to be possibly due to stimulation of differentiation and suppression of proliferation.

  10. Recovery and Cultivation of Keratinocytes From Shipped Mouse Skin.

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    Yang, Hsin-Ya; La, Thi Dinh; Gurenko, Zhanna; Steenhuis, Pieter; Liu, Wei; Isseroff, R Rivkah

    2015-02-01

    Murine keratinocyte culture from neonatal skin is an important tool for studying the functional role of specific genes in epithelial biology. However, when the transgenic animal is only available in a geographically distant local, obtaining viable keratinocytes can be problematic. A method for transferring the isolated murine skin from collaborating labs could decrease the cost of shipping live animals, and would allow the efficient use of the tissues from the transgenic animals. Here we optimized shipping conditions and characterized the cells retrieved and cultured from mouse skin shipped for 48 h at 0 °C. The cultured keratinocytes from the control, non-shipped skin and the 2-day shipped skin were 43.6 +/- 7.8% viable, doubled every 2 days, and expressed comparable amounts of heat shock proteins and CD29/integrin beta-1. However, under the same shipping conditions, the 3-day shipped tissue failed to establish colonies in the culture. Therefore, this 2-day shipping technique allows the transfer mouse skin from distant locations with recovery of viable, propagatable keratinocytes, facilitating long-distance collaborations.

  11. Notch1 functions as a tumor suppressor in mouse skin.

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    Nicolas, Michael; Wolfer, Anita; Raj, Kenneth; Kummer, J Alain; Mill, Pleasantine; van Noort, Mascha; Hui, Chi-chung; Clevers, Hans; Dotto, G Paolo; Radtke, Freddy

    2003-03-01

    Notch proteins are important in binary cell-fate decisions and inhibiting differentiation in many developmental systems, and aberrant Notch signaling is associated with tumorigenesis. The role of Notch signaling in mammalian skin is less well characterized and is mainly based on in vitro studies, which suggest that Notch signaling induces differentiation in mammalian skin. Conventional gene targeting is not applicable to establishing the role of Notch receptors or ligands in the skin because Notch1-/- embryos die during gestation. Therefore, we used a tissue-specific inducible gene-targeting approach to study the physiological role of the Notch1 receptor in the mouse epidermis and the corneal epithelium of adult mice. Unexpectedly, ablation of Notch1 results in epidermal and corneal hyperplasia followed by the development of skin tumors and facilitated chemical-induced skin carcinogenesis. Notch1 deficiency in skin and in primary keratinocytes results in increased and sustained expression of Gli2, causing the development of basal-cell carcinoma-like tumors. Furthermore, Notch1 inactivation in the epidermis results in derepressed beta-catenin signaling in cells that should normally undergo differentiation. Enhanced beta-catenin signaling can be reversed by re-introduction of a dominant active form of the Notch1 receptor. This leads to a reduction in the signaling-competent pool of beta-catenin, indicating that Notch1 can inhibit beta-catenin-mediated signaling. Our results indicate that Notch1 functions as a tumor-suppressor gene in mammalian skin.

  12. Metabolism of skin-absorbed resveratrol into its glucuronized form in mouse skin.

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    Itsuo Murakami

    Full Text Available Resveratrol (RESV is a plant polyphenol, which is thought to have beneficial metabolic effects in laboratory animals as well as in humans. Following oral administration, RESV is immediately catabolized, resulting in low bioavailability. This study compared RESV metabolites and their tissue distribution after oral uptake and skin absorption. Metabolomic analysis of various mouse tissues revealed that RESV can be absorbed and metabolized through skin. We detected sulfated and glucuronidated RESV metabolites, as well as dihydroresveratrol. These metabolites are thought to have lower pharmacological activity than RESV. Similar quantities of most RESV metabolites were observed 4 h after oral or skin administration, except that glucuronidated RESV metabolites were more abundant in skin after topical RESV application than after oral administration. This result is consistent with our finding of glucuronidated RESV metabolites in cultured skin cells. RESV applied to mouse ears significantly suppressed inflammation in the TPA inflammation model. The skin absorption route could be a complementary, potent way to achieve therapeutic effects with RESV.

  13. Analysis of a Mouse Skin Model of Tuberous Sclerosis Complex

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    Guo, Yanan; Dreier, John R.; Cao, Juxiang; Du, Heng; Granter, Scott R.; Kwiatkowski, David J.

    2016-01-01

    Tuberous Sclerosis Complex (TSC) is an autosomal dominant tumor suppressor gene syndrome in which patients develop several types of tumors, including facial angiofibroma, subungual fibroma, Shagreen patch, angiomyolipomas, and lymphangioleiomyomatosis. It is due to inactivating mutations in TSC1 or TSC2. We sought to generate a mouse model of one or more of these tumor types by targeting deletion of the Tsc1 gene to fibroblasts using the Fsp-Cre allele. Mutant, Tsc1ccFsp-Cre+ mice survived a median of nearly a year, and developed tumors in multiple sites but did not develop angiomyolipoma or lymphangioleiomyomatosis. They did develop a prominent skin phenotype with marked thickening of the dermis with accumulation of mast cells, that was minimally responsive to systemic rapamycin therapy, and was quite different from the pathology seen in human TSC skin lesions. Recombination and loss of Tsc1 was demonstrated in skin fibroblasts in vivo and in cultured skin fibroblasts. Loss of Tsc1 in fibroblasts in mice does not lead to a model of angiomyolipoma or lymphangioleiomyomatosis. PMID:27907099

  14. A method for the immortalization of newborn mouse skin keratinocytes

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    Brianna O Hammiller

    2015-07-01

    Full Text Available Isolation and culture of mouse primary epidermal keratinocytes is a common technique that allows for easy genetic and environmental manipulation. However, due to their limited lifespan in culture, experiments utilizing primary keratinocytes require large numbers of animals, and are time consuming and expensive. To avoid these issues, we developed a method for the immortalization of primary mouse epidermal keratinocytes. Upon isolation of newborn epidermal keratinocytes according to established methods, the cells were cultured long-term in keratinocyte growth factor-containing medium. The cells senesced within a few weeks and eventually, small, slowly growing colonies emerged. After they regained confluency, the cells were passaged and slowly refilled the dish. With several rounds of subculture, the cells adapted to culture conditions, were easily subcultured, maintained normal morphology, and were apparently immortal. The immortalized cells retained the ability to differentiate with increased calcium concentrations, and were maintained to high passage numbers, while maintaining a relatively stable karyotype. Analysis of multiple immortalized cell lines as well as primary keratinocyte cultures, revealed increased numbers of chromosomes, especially in the primary keratinocytes, and chromosomal aberrations in most of the immortalized cultures and in the primary keratinocytes. Orthotopic grafting of immortalized keratinocytes together with fibroblasts onto nude mouse hosts produced skin while v-rasHa infection of the immortalized keratinocytes prior to grafting produced squamous cell carcinoma. In summary, this method of cell line generation allows for decreased use of animals, reduces the expense and time involved in research, and provides a useful model for cutaneous keratinocyte experimentation.

  15. Mouse skin damages caused by fractionated irradiation with carbon ions

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    Ando, K.; Chen, Y.J.; Ohira, C.; Nojima, K.; Ando, S.; Kobayashi, N.; Ohbuchi, T.; Shimizu, W. [Space and Particle Radiation Science Research Group, Chiba (Japan); Koike, S.; Kanai, T. [National Inst. of Radiological Sciences, Chiba (Japan). Div. of Accelerator Physics

    1997-09-01

    We have investigated carbon-dose responses of early and late skin damages after daily fractionations to the mouse leg. Depilated legs were irradiated with 7 different positions within 290 MeV/u carbon beams. Fractionation schedules were 1, 2, 4 and 8 daily fractions. Skin reaction was scored every other day for 32 days. Five highest scores in individual mice were averaged, and used as averaged peak reaction. The isoeffect doses to produce an averaged peak skin reaction of 3.0 (moist desquamation) on dose-response curves were calculated with 95% confidence limit. The isoeffect dose for control gamma rays constantly increased with an increase in the number of fraction. The isoeffect doses in low LET carbon ions of 14- and 20 keV/{mu}m also increased up to 4 fractions, but did not increase when 4 fractions increased to 8 fractions. The saturation of isoeffect dose was more prominently observed for 40 keV/{mu}m in such that the isoeffect doses did not change among 2, 4 and 8 fractions. The isoeffect doses for LET higher than 50 keV/{mu}m were smaller than those for lower LET. However, the isoeffect doses for 50-, 60-, 80- and 100 keV/{mu} steadily increased with an increase in the number of fraction and did not show any saturation up to 8 fractions. Relation between LET and RBE was linear for all fractionation schedules. The slope of regression line in 4 fractions was steepest, and significantly (P<0.05) different from that in 1 fraction. (orig.)

  16. Mouse Genetic Models Reveal Surprising Functions of IκB Kinase Alpha in Skin Development and Skin Carcinogenesis

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    Xia, Xiaojun [The Methodist Hospital Research Institute, Houston, TX 77030 (United States); Park, Eunmi [Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 (United States); Fischer, Susan M. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78967 (United States); Hu, Yinling, E-mail: huy2@mail.nih.gov [Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21701 (United States)

    2013-02-15

    Gene knockout studies unexpectedly reveal a pivotal role for IκB kinase alpha (IKKα) in mouse embryonic skin development. Skin carcinogenesis experiments show that Ikkα heterozygous mice are highly susceptible to chemical carcinogen or ultraviolet B light (UVB) induced benign and malignant skin tumors in comparison to wild-type mice. IKKα deletion mediated by keratin 5 (K5).Cre or K15.Cre in keratinocytes induces epidermal hyperplasia and spontaneous skin squamous cell carcinomas (SCCs) in Ikkα floxed mice. On the other hand, transgenic mice overexpressing IKKα in the epidermis, under the control of a truncated loricrin promoter or K5 promoter, develop normal skin and show no defects in the formation of the epidermis and other epithelial organs, and the transgenic IKKα represses chemical carcinogen or UVB induced skin carcinogenesis. Moreover, IKKα deletion mediated by a mutation, which generates a stop codon in the Ikkα gene, has been reported in a human autosomal recessive lethal syndrome. Downregulated IKKα and Ikkα mutations and deletions are found in human skin SCCs. The collective evidence not only highlights the importance of IKKα in skin development, maintaining skin homeostasis, and preventing skin carcinogenesis, but also demonstrates that mouse models are extremely valuable tools for revealing the mechanisms underlying these biological events, leading our studies from bench side to bedside.

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

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    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.

  18. Histochemical Localization of Glutathione Dependent NBT-Reductase in Mouse Skin

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective Localization of the glutathione dependent Nitroblue tetrazolium (NBT) reductase in fresh frozen sections of mouse skin and possible dependence of NBT reductase on tissue thiol levels has been investigated. Methods The fresh frozen tissue sections (8m thickness) were prepared and incubated in medium containing NBT, reduced glutathione (GSH) and phosphate buffer. The staining for GSH was performed with mercury orange. Results  The activity of the NBT-reductase in mouse skin has been found to be localized in the areas rich in glutathione and actively proliferating area of the skin. Conclusion The activity of the NBT-reductase seems to be dependent on the glutathione contents.

  19. Matrine inhibits proliferation of mouse skin fibroblasts induced by platelet-derived growth factor-BB

    Institute of Scientific and Technical Information of China (English)

    WU Yan-an; GAO Chun-fang; WANG Hao; HUANG Chao; KONG Xian-tao

    2001-01-01

    To study the effect of matrine on proliferation of mouse skin fibroblasts induced by platelet-derived growth factor-BB (PDGF-BB). Methods: Mouse skin fibroblasts were obtained from newborn ⅠCR mice and propagated in vitro. Proliferation of cell was analyzed by mitochondrial reduction of tetrazolium salt MTT and actual cell count. Results: Matrine (50 to 500 μg/ml) caused dose-dependent reduction of serum-stimulated cell growth. Growth inhibition was totally reversed after removal of the drug. Matrine also inhibited PDGF-BB induced cell growth dose-dependently. Conclusion: Matrine exhibits potent anti-proliferation effect on mouse skin fibroblast. This effect appears to be mediated by decrease of PDGF-induced growth. These results suggest that matrine might have preventive and therapeutic implication in skin fibrosis.

  20. Collagen Content in Skin and Internal Organs of the Tight Skin Mouse: An Animal Model of Scleroderma

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    Jayanthi Manne

    2013-01-01

    Full Text Available The Tight Skin mouse is a genetically induced animal model of tissue fibrosis caused by a large in-frame mutation in the gene encoding fibrillin-1 (Fbn-1. We examined the influence of gender on the collagen content of tissues in C57BL/6J wild type (+/+ and mutant Tight Skin (Tsk/+ mice employing hydroxyproline assays. Tissue sections were stained with Masson’s trichrome to identify collagen in situ. Adult Tsk/+ mice skin contains ~15% more collagen, on average, than skin from +/+ mice of the same gender. The heart of Tsk/+ males had significantly more collagen than that of +/+ males. No significant gender differences were found in lungs and kidney collagen content. Overall, the collagen content of Tsk/+ males and +/+ males was higher than that of their Tsk/+ and +/+ female counterparts, respectively. Our data confirm increased deposition of collagen in skin and hearts of Tsk/+ mice; however, the effects of the Tsk mutation on collagen content are both tissue specific and gender specific. These results indicate that comparative studies of collagen content between normal and Tsk/+ mice skin and internal organs must take into account gender differences caused by expression of the androgen receptor.

  1. Compression-induced HIF-1 enhances thrombosis and PAI-1 expression in mouse skin.

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    Kaneko, Maki; Minematsu, Takeo; Yoshida, Mikako; Nishijima, Yoshimi; Noguchi, Hiroshi; Ohta, Yasunori; Nakagami, Gojiro; Mori, Taketoshi; Sanada, Hiromi

    2015-09-01

    Pressure ulcers result from tissue hypoxia caused by external forces. Thrombosis due to external forces is considered important, and hypoxia inducible factor-1 (HIF-1) is a master regulator of pressure ulcer development. To date, however, their causal relationship has not been determined. This study therefore investigated the mutual relationship between thrombosis and HIF-1 activation in compressed mouse skin, based on a hypothesis that HIF-1 regulation by plasminogen activator inhibitor-1 (PAI-1) enhances thrombosis. Compression of mouse skin significantly increased the numbers of thrombi and HIF-1α-positive cells compared with control skin. A thrombosis inhibitor significantly reduced the numbers of HIF-1α-positive cells and an HIF-1 inhibitor significantly inhibited thrombosis in compressed skin tissue, suggesting a mutual relationship between thrombosis and HIF-1 activation. Compression of mouse skin also enhanced the level of Pai-1 messenger RNA expression, but this increase was significantly reduced by treatment with an HIF-1 inhibitor, whereas a thrombosis inhibitor had no effect. These results suggested the involvement of PAI-1 in HIF-1-enhanced thrombosis and that an additional factor participates in regulating Pai-1 expression in compressed skin. These findings may suggest new strategies in pressure ulcer management.

  2. Preparation of Single-cell Suspensions for Cytofluorimetric Analysis from Different Mouse Skin Regions.

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    Broggi, Achille; Cigni, Clara; Zanoni, Ivan; Granucci, Francesca

    2016-04-20

    The skin is a barrier organ that interacts with the external environment. Being continuously exposed to potential microbial invasion, the dermis and epidermis home a variety of immune cells in both homeostatic and inflammatory conditions. Tools to obtain skin cell release for cytofluorimetric analyses are, therefore, very useful in order to study the complex network of immune cells residing in the skin and their response to microbial stimuli. Here, we describe an efficient methodology for the digestion of mouse skin to rapidly and efficiently obtain single-cell suspensions. This protocol allows maintenance of maximum cell viability without compromising surface antigen expression. We also describe how to take and digest skin samples from different anatomical locations, such as the ear, trunk, tail, and footpad. The obtained suspensions are then stained and analyzed by flow cytometry to discriminate between different leukocyte populations.

  3. Protective effects of black rice bran against chemically-induced inflammation of mouse skin

    Science.gov (United States)

    We investigated the inhibitory effects of black rice (cv. LK1-3-6-12-1-1) bran against 12-O-tetradecanolylphorbol-13-acetate (TPA)-induced skin edema and 2,4-dinitroflurobenzene (DNFB)-induced allergic contact dermatitis (ACD) in inflammatory mouse models. We also determined the effects of the bran...

  4. The optical properties of mouse skin in the visible and near infrared spectral regions.

    Science.gov (United States)

    Sabino, Caetano P; Deana, Alessandro M; Yoshimura, Tania M; da Silva, Daniela F T; França, Cristiane M; Hamblin, Michael R; Ribeiro, Martha S

    2016-07-01

    Visible and near-infrared radiation is now widely employed in health science and technology. Pre-clinical trials are still essential to allow appropriate translation of optical methods into clinical practice. Our results stress the importance of considering the mouse strain and gender when planning pre-clinical experiments that depend on light-skin interactions. Here, we evaluated the optical properties of depilated albino and pigmented mouse skin using reproducible methods to determine parameters that have wide applicability in biomedical optics. Light penetration depth (δ), absorption (μa), reduced scattering (μ's) and reduced attenuation (μ't) coefficients were calculated using the Kubelka-Munk model of photon transport and spectrophotometric measurements. Within a broad wavelength coverage (400-1400nm), the main optical tissue interactions of visible and near infrared radiation could be inferred. Histological analysis was performed to correlate the findings with tissue composition and structure. Disperse melanin granules present in depilated pigmented mouse skin were shown to be irrelevant for light absorption. Gender mostly affected optical properties in the visible range due to variations in blood and abundance of dense connective tissue. On the other hand, mouse strains could produce more variations in the hydration level of skin, leading to changes in absorption in the infrared spectral region. A spectral region of minimal light attenuation, commonly referred as the "optical window", was observed between 600 and 1350nm.

  5. D-aspartic acid in aged mouse skin and lens

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Noriko; Muraoka, Shiro; Harada, Kaoru; Tamanoi, Itsuro; Joshima, Hisamasa; Kashima, Masatoshi

    1987-03-01

    D-aspartic acid (D-Asp) was detected in the skin and lens from naturally aged mice. An analysis of the amino acid composition indicated that D-Asp did not derive from collagen. An immunological analysis using Oucterlony's agar diffusion method also confirmed that the protein containing D-Asp was not a serum protein. The process producing D-Asp is regarded as one other than racemization because the life span of mice is not long enough to permit D-Asp by racemization. Continuous low-dose-rate gamma-irradiation (37R per day) for 102 to 112 days did not increase significantly the amount of D-Asp in skin and lens of mice.

  6. Histochemical Localization of Glutathione Dependent NBT—Reductase in Mouse Skin

    Institute of Scientific and Technical Information of China (English)

    YOESHWERSHUKLA

    2001-01-01

    Objective:Localization of the glutathione dependent Nitroblue tetrazolium(NBT) reductase in fresh frozen sections of mouse skin and possible dependence of NBT reductase on tissue thiol levels has been investigated.Methods:The fresh frozen tissue sections(8m thickness)were prepared and incuated in medium containing NBT,reduced glutathione(GSH) and Phosphate uffer,The staining for GSH was performed with mercury orange.Results:The activity of the NBT-reductase in mouse skin has een found to be localized in the areas rich in glutatione and actively proliferating area of the skin.Conclusion:The activity of the NBT-reductase seems to be dependent on the glutatione contents.

  7. Delayed tail loss during the invasion of mouse skin by cercariae of Schistosoma japonicum.

    Science.gov (United States)

    Wang, Ting; Fang, Zheng-Ming; Lei, Jia-Hui; Guan, Fei; Liu, Wen-Qi; Bartlett, Ann; Whitfield, Phil; Li, Yong-Long

    2012-02-01

    A traditional assumption is that schistosome cercariae lose their tails at the onset of penetration. It has, however, recently been demonstrated that, for Schistosoma mansoni, cercarial tails were not invariably being shed as penetration took place and a high proportion of tails entered human skin under experimental conditions. This phenomenon was termed delayed tail loss (DTL). In this paper, we report that DTL also happens with S. japonicum cercariae during penetration of mouse skin. It occurred at all cercarial densities tested, from as few as 10 cercariae/2·25 cm(2) of mouse skin up to 200 cercariae. Furthermore, it was demonstrated that there was a density-dependent increase in DTL as cercarial densities increased. No such density-dependent enhancement was shown for percentage attachment over the same cercarial density range.

  8. The biodisposition and hypertrichotic effects of bimatoprost in mouse skin.

    Science.gov (United States)

    Woodward, David F; Tang, Elaine S-H; Attar, Mayssa; Wang, Jenny W

    2013-02-01

    Studies on bimatoprost were performed with two objectives: (i) to determine whether bimatoprost possesses hair growth-stimulating properties beyond eyelash hypertrichosis and (ii) to investigate the biodisposition of bimatoprost in skin for the first time. Bimatoprost, at the dose used clinically for eyelash growth (0.03%) and given once daily for 14 days, increased pelage hair growth in C57/black 6 mice. This occurred as a much earlier onset of new hair growth in shaved mice and the time taken to achieve complete hair regrowth, according to photographic documentation and visual assessment. Bimatoprost biodisposition in the skin was determined at three concentrations: 0.01%, 0.03% and 0.06%. Dose-dependent C(max) values were obtained (3.41, 6.74, 12.3 μg/g tissue), and cutaneous bimatoprost was well maintained for 24 h following a single dose. Bimatoprost was recovered from the skin only as the intact molecule, with no detectable levels of metabolites. Thus, bimatoprost produces hypertrichosis as the intact molecule.

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

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Anil K.; Tewari-Singh, Neera; Inturi, Swetha; Kumar, Dileep [Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States); Orlicky, David J. [Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States); Agarwal, Chapla [Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States); White, Carl W. [Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045USA (United States); Agarwal, Rajesh, E-mail: Rajesh.Agarwal@UCDenver.edu [Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States)

    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

  10. Tumor initiating and promoting activities of various benzo(a)pyrene metabolites in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Slaga, T J; Bracken, W M; Viaje, A; Berry, D L; Fischer, S M; Miller, D R; Levin, W; Conney, A H; Yagi, H; Jerina, D M

    1977-01-01

    The skin tumor-initiating activities of the twelve isomeric phenols of BP revealed that 2-OHBP was as potent as BP while 11-OHBP was moderately active and the others were weak or inactive. However, 2-OHBP has not been shown to be formed from BP in the skin or any other tissue. The (-)-trans-7,8-diol of BP skin was found to be more active as a skin tumor initiator than BP suggesting that it is a proximal carcinogen. The data on carcinogenicity, mutagenicity and metabolism suggest that BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide is the ultimate carcinogenic form of BP. The skin tumor-initiating activities of the various BP metabolites correlate very well with their complete carcinogenic in mouse skin except for BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide. It was found to have skin tumor initiating activity but not complete carcinogenic activity. However, BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide was found to be a very potent complete carcinogen in newborn mice. It is possible that BP-7..beta.., 8..cap alpha..-diol-9..cap alpha.., 10..cap alpha..-epoxide is only a tumor initiator in which a promoting stimulus must be supplied for carcinogenic activity. A natural tumor promoting stimulus may be present in the newborn mouse. There is also a good correlation between the skin tumor initiating activities of the various BP metabolites and their mutagenic activity in the V79 mammalian cell mediated mutagenesis system.

  11. Development of a Bioengineered Skin-Humanized Mouse Model for Psoriasis : Dissecting Epidermal-Lymphocyte Interacting Pathways

    OpenAIRE

    Guerrero-Aspizua, Sara; García, Marta; Murillas, Rodolfo; Retamosa, Luisa; Illera, Nuria; Duarte, Blanca; Holguín, Almudena; Puig, Susana; Hernández, Maria Isabel; Meana, Alvaro; Jorcano, Jose Luis; Larcher, Fernando; Carretero, Marta; del Río, Marcela

    2010-01-01

    Over the past few years, whole skin xenotransplantation models that mimic different aspects of psoriasis have become available. However, these models are strongly constrained by the lack of skin donor availability and homogeneity. We present in this study a bioengineering-based skin-humanized mouse model for psoriasis, either in an autologous version using samples derived from psoriatic patients or, more importantly, in an allogeneic context, starting from skin biopsies and blood samples from...

  12. High-power femtosecond-terahertz pulse induces a wound response in mouse skin

    Science.gov (United States)

    Kim, Kyu-Tae; Park, Jaehun; Jo, Sung Jin; Jung, Seonghoon; Kwon, Oh Sang; Gallerano, Gian Piero; Park, Woong-Yang; Park, Gun-Sik

    2013-08-01

    Terahertz (THz) technology has emerged for biomedical applications such as scanning, molecular spectroscopy, and medical imaging. Although a thorough assessment to predict potential concerns has to precede before practical utilization of THz source, the biological effect of THz radiation is not yet fully understood with scant related investigations. Here, we applied a femtosecond-terahertz (fs-THz) pulse to mouse skin to evaluate non-thermal effects of THz radiation. Analysis of the genome-wide expression profile in fs-THz-irradiated skin indicated that wound responses were predominantly mediated by transforming growth factor-beta (TGF-β) signaling pathways. We validated NFκB1- and Smad3/4-mediated transcriptional activation in fs-THz-irradiated skin by chromatin immunoprecipitation assay. Repeated fs-THz radiation delayed the closure of mouse skin punch wounds due to up-regulation of TGF-β. These findings suggest that fs-THz radiation initiate a wound-like signal in skin with increased expression of TGF-β and activation of its downstream target genes, which perturbs the wound healing process in vivo.

  13. Skin barrier disruption by acetone: observations in a hairless mouse skin model

    NARCIS (Netherlands)

    Rissmann, R.; Oudshoorn, M.H.M.; Hennink, W.E.; Ponec, M.; Bouwstra, J.A.

    2009-01-01

    To disrupt the barrier function of the skin, different in vivo methods have been established, e.g., by acetone wiping or tape-stripping. In this study, the acetone-induced barrier disruption of hairless mice was investigated in order to establish a reliable model to study beneficial, long-term effec

  14. Curcumin Stimulates the Antioxidant Mechanisms in Mouse Skin Exposed to Fractionated γ-Irradiation

    Directory of Open Access Journals (Sweden)

    Ganesh Chandra Jagetia

    2015-01-01

    Full Text Available Fractionated irradiation is one of the important radiotherapy regimens to treat different types of neoplasia. Despite of the immense therapeutic gains accrued by delivering fractionated irradiation to tumors, the radiation burden on skin increases significantly. Low doses of irradiation to skin adversely affect its molecular and metabolic status. The use of antioxidant/s may help to alleviate the radiation-induced changes in the skin and allow delivering a higher dose of radiation to attain better therapeutic gains. Curcumin is an antioxidant and a free radical scavenging dietary supplement, commonly used as a flavoring agent in curries. Therefore, the effect of 100 mg/kg body weight curcumin was studied on the antioxidant status of mice skin exposed to a total dose of 10, 20 and 40 Gy γ-radiation below the rib cage delivered as a single fraction of 2 Gy per day for 5, 10 or 20 days. Skin biopsies from both the curcumin treated or untreated irradiated groups were collected for the biochemical estimations at various post-irradiation times. The irradiation of animals caused a dose dependent decline in the glutathione concentration, glutathione peroxidase, and superoxide dismutase activities and increased the lipid peroxidation in the irradiated skin. Curcumin treatment before irradiation resulted in a significant rise in the glutathione concentration and activities of both the glutathione peroxidase and superoxide dismutase enzymes in mouse skin, whereas lipid peroxidation declined significantly. The present study indicates that curcumin treatment increased the antioxidant status of mouse exposed to different doses of fractionated γ-radiation.

  15. In Vivo SILAC-Based Proteomics Reveals Phosphoproteome Changes during Mouse Skin Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Sara Zanivan

    2013-02-01

    Full Text Available Cancer progresses through distinct stages, and mouse models recapitulating traits of this progression are frequently used to explore genetic, morphological, and pharmacological aspects of tumor development. To complement genomic investigations of this process, we here quantify phosphoproteomic changes in skin cancer development using the SILAC mouse technology coupled to high-resolution mass spectrometry. We distill protein expression signatures from our data that distinguish between skin cancer stages. A distinct phosphoproteome of the two stages of cancer progression is identified that correlates with perturbed cell growth and implicates cell adhesion as a major driver of malignancy. Importantly, integrated analysis of phosphoproteomic data and prediction of kinase activity revealed PAK4-PKC/SRC network to be highly deregulated in SCC but not in papilloma. This detailed molecular picture, both at the proteome and phosphoproteome level, will prove useful for the study of mechanisms of tumor progression.

  16. Topical application of ochratoxin A causes DNA damage and tumor initiation in mouse skin.

    Directory of Open Access Journals (Sweden)

    Rahul Kumar

    Full Text Available Skin cancer is one of the most common forms of cancer and 2-3 million new cases are being diagnosed globally each year. Along with UV rays, environmental pollutants/chemicals including mycotoxins, contaminants of various foods and feed stuffs, could be one of the aetiological factors of skin cancer. In the present study, we evaluated the DNA damaging potential and dermal carcinogenicity of a mycotoxin, ochratoxin A (OTA, with the rationale that dermal exposure to OTA in workers may occur during their involvement in pre and post harvest stages of agriculture. A single topical application of OTA (20-80 µg/mouse resulted in significant DNA damage along with elevated γ-H2AX level in skin. Alteration in oxidative stress markers such as lipid peroxidation, protein carbonyl, glutathione content and antioxidant enzymes was observed in a dose (20-80 µg/mouse and time-dependent (12-72 h manner. The oxidative stress was further emphasized by the suppression of Nrf2 translocation to nucleus following a single topical application of OTA (80 µg/mouse after 24 h. OTA (80 µg/mouse application for 12-72 h caused significant enhancement in- (a reactive oxygen species generation, (b activation of ERK1/2, p38 and JNK MAPKs, (c cell cycle arrest at G0/G1 phase (37-67%, (d induction of apoptosis (2.0-11.0 fold, (e expression of p53, p21/waf1, (f Bax/Bcl-2 ratio, (g cytochrome c level, (h activities of caspase 9 (1.2-1.8 fold and 3 (1.7-2.2 fold as well as poly ADP ribose polymerase cleavage. In a two-stage mouse skin tumorigenesis protocol, it was observed that a single topical application of OTA (80 µg/mouse followed by twice weekly application of 12-O-tetradecanoylphorbol-13-acetate for 24 week leads to tumor formation. These results suggest that OTA has skin tumor initiating property which may be related to oxidative stress, MAPKs signaling and DNA damage.

  17. Immunoprotective UVA (320-400 nm) irradiation upregulates heme oxygenase-1 in the dermis and epidermis of hairless mouse skin.

    Science.gov (United States)

    Allanson, Munif; Reeve, Vivienne E

    2004-04-01

    The induction of heme oxygenase-1 (HO-1) by ultraviolet A (UVA) (320-400 nm) radiation provides a protective cellular defence against oxidative stress, and has been well demonstrated in cultured human skin fibroblasts, although keratinocytes were unreactive. The UVA responsiveness of HO-1 however, has not been confirmed in intact skin. Previously, we reported that UVA-inducible HO enzyme activity in mouse skin is protective against UVB-induced immunosuppression. This study identifies the induced HO isoform and its localization in mouse skin irradiated in vivo with such an immunoprotective UVA dose. We found that HO-1 mRNA was expressed in UVA-irradiated skin, but not in normal or UVB-irradiated skin, whereas constitutive HO-2 was always present. UVA-irradiated skin had increased HO enzyme activity and bilirubin content, and decreased heme content, consistent with HO-1 induction. In situ hybridization and immunohistochemical staining localized HO-1 mRNA and protein to both epidermis and dermis, with strongest expression in basal keratinocytes and weaker expression in dermal fibroblast-like and other cells, in contrast with UVA-induced HO-1 in cultured human skin fibroblasts. This suggests that cultured skin cells may not fully represent skin functions in vivo, or that there may be inherent differences between human and hairless mouse skin HO-1 responses.

  18. Induction of megakaryocytic colony-stimulating activity in mouse skin by inflammatory agents and tumor promoters

    Energy Technology Data Exchange (ETDEWEB)

    Clark, D.A.; Dessypris, E.N.; Koury, M.J.

    1987-03-01

    The production of megakaryocytic colony-stimulating activity (MEG-CSA) was assayed in acetic acid extracts of skin from mice topically treated with inflammatory and tumor-promoting agents. A rapid induction of MEG-CSA was found in skin treated both with phorbol 12-myristate 13-acetate (PMA), a strong tumor promoter, and with mezerein, a weak tumor promoter, but no induction was found in untreated skin. The time course of induction of MEG-CSA following treatment of skin with PMA or mezerein was very similar to that previously demonstrated for the induction of granulocyte-macrophage colony-stimulating activity in mouse skin by these agents. The induced MEG-CSA was found in both the epidermis and the dermis. Pretreatment of the skin with US -methasone abrogated the MEG-CSA induction. The cell number response curve suggests that the MEG-CSA acts directly on the progenitor cells of the megakaryocyte colonies. That topical administration of diterpene esters results in the rapid, local induction of MEG-CSA which can be blocked by US -methasone pretreatment suggests a mechanism for the thrombocytosis associated with some inflammatory states. The indirect action in which diterpene esters induce in certain cells the production or release of growth regulatory factors for other cell types may also aid in understanding their carcinogenic properties.

  19. Ultraviolet light induction of skin carcinoma in the mouse; influence of cAMP modifying agents.

    Science.gov (United States)

    Zajdela, F; Latarjet, R

    1978-01-01

    A short review of pathogenic factors in U.V. light skin carcinogenesis in the mouse is presented. Caffeine and theophylline applied locally during U.V. irradiation caused a 50 percent reduction of skin tumour induction in Swiss mice. These two chemicals are inhibitors of DNA postreplication repair, but they also raise the intracellular level of cyclic AMP by inhibiting cAMP phosphodiesterase with, as a consequence, a possible slowing down of cellular growth. Control experiments using three different chemicals capable of raising the cAMP level in epidermal cells gave negative results. These experimental data are compatible with our original hypothesis according to which production of skin cancers by U.V. radiation is in same way related to DNA repair which helps the cell to survive but allows or favours the occurrence of errors in cellular DNA.

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

    Science.gov (United States)

    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

  1. An Improved Mouse Model of Atopic Dermatitis and Suppression of Skin Lesions by an Inhibitor of Tec Family Kinases

    Directory of Open Access Journals (Sweden)

    Yuko Kawakami

    2007-01-01

    Conclusions: We established a highly efficient, highly reproducible protocol to induce skin lesions in NC/Nga mice and successfully applied it to show the efficacy of terreic acid in treating skin lesions. This mouse model of atopic dermatitis will be useful to study the pathogenetic processes of atopic dermatitis and to evaluate the efficacy of drug candidates.

  2. Long-term maintenance of skin immune system in a NOD-Scid IL2rγ(null) mouse model transplanted with human skin.

    Science.gov (United States)

    Soria, Angèle; Boccara, David; Chonco, Louis; Yahia, Nora; Dufossée, Mélody; Cardinaud, Sylvain; Moris, Arnaud; Liard, Christelle; Joulin-Giet, Alix; Julithe, Marion; Mimoun, Maurice; Combadière, Béhazine; Perrin, Hélène

    2014-11-01

    We developed a NOD-Scid IL2rγ(null) mouse model transplanted with human skin that brings fundamental insight on in vivo cellular mechanisms of intradermal immunization and antigen presentation by dermal dendritic and epidermal Langerhans cells for skin T-cell immunity. Indeed, T-cell immunity is a crucial checkpoint for the induction of in vivo rapid control of skin infection. With the long-term preservation of a complete human skin immune system, this model offers the unique opportunity not only to better understand mechanisms of skin immune response but also to test new compounds and devices for cutaneous routes of vaccination, as well as new therapeutics approach for skin diseases, allergies or infections.

  3. Pharmacological inhibition of DGAT1 induces sebaceous gland atrophy in mouse and dog skin while overt alopecia is restricted to the mouse.

    Science.gov (United States)

    Floettmann, Eike; Lees, David; Seeliger, Frank; Jones, Huw Bowen

    2015-04-01

    Diacylglycerol O-acyltransferase 1 (DGAT1) plays an important role in synthesizing lipids, and inhibitors of DGAT1 have been investigated as potential treatments for diabetes and metabolic diseases. DGAT1 knockout (-/-) mice are resistant to obesity, have increased sensitivity to insulin, and exhibit sebaceous gland atrophy and alopecia. Prolonged pharmacological inhibition of DGAT1 with AZD7687 in mice results in the same skin phenotype, including sebaceous gland atrophy and alopecia, as seen in the skin of DGAT1 (-/-) mice. AZD7687-mediated effects on the skin were dose- and time-dependent and reversible. They occurred only at substantial levels of continuous DGAT1 inhibition. Prolonged treatment of dogs with AZD7687 also resulted in sebaceous gland atrophy but did not result in the more adverse skin changes of hair loss and skin lesions. Our findings highlight a significant risk of generating the same lesions that were seen in mouse skin during clinical development of DGAT1 inhibitors in humans and also reveal a species difference in the effects on the skin, indicating that the mouse may be an especially sensitive species. Therefore, although human therapeutic doses may not have the same influence on skin morphology as seen in mice, monitoring of skin changes will be essential in clinical trials with DGAT1 inhibitors.

  4. Effects of Nicotinamide on Mouse Skin Tumor Development and lts Mode of Action

    Institute of Scientific and Technical Information of China (English)

    KRISHNA P. GUPTA

    1999-01-01

    Nicotinamide (NA), a naturally occuring vitamin and a protease inhibitor, has been shown to be effective in treating some skin ailments. It inhibits cell proliferation and induces cell differentiation. This report shows the effects of NA on mouse skin tumor development and on the critical events involved in this process. NA reduced tumor growth, inhibited the 12-O-tetradecanoylphorbol- 13-acetate (TPA) induced ornithine decarboxylase activity, but induced the transglutaminase activity which was inhibited by TPA under different experimental conditions.The effects of NA on ornithine decarboxylase (ODC) and transglutaminase (TG) indicated that nicotinamide (NA) probably programmmed the cells for their death in the natural course of time, I.e. Programed cell death. This observation indicates that NA might be a better agent for the detailed study and for the better use in prevention of cancer alone or in combination with other drugs.

  5. Deoxynivalenol induced mouse skin cell proliferation and inflammation via MAPK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, Sakshi [Food Drug and Chemical Toxicology, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box No. 80, Mahatma Gandhi Marg, Lucknow 226 001 (India); Department of Biochemistry, Banaras Hindu University (BHU), Varanasi (India); Tripathi, Anurag [Food Drug and Chemical Toxicology, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box No. 80, Mahatma Gandhi Marg, Lucknow 226 001 (India); Chaudhari, Bhushan P. [Pathology Laboratory, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Mahatma Gandhi Marg, PO Box 80, Lucknow 226001, Uttar Pradesh (India); Dwivedi, Premendra D. [Food Drug and Chemical Toxicology, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box No. 80, Mahatma Gandhi Marg, Lucknow 226 001 (India); Pandey, Haushila P. [Department of Biochemistry, Banaras Hindu University (BHU), Varanasi (India); Das, Mukul, E-mail: mditrc@rediffmail.com [Food Drug and Chemical Toxicology, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), P.O. Box No. 80, Mahatma Gandhi Marg, Lucknow 226 001 (India)

    2014-09-01

    Several toxicological manifestations of deoxynivalenol (DON), a mycotoxin, are well documented; however, dermal toxicity is not yet explored. The effect of topical application of DON to mice was studied using markers of skin proliferation, inflammation and tumor promotion. Single topical application of DON (84–672 nmol/mouse) significantly enhanced dermal hyperplasia and skin edema. DON (336 and 672 nmol) caused significant enhancement in [{sup 3}H]-thymidine uptake in DNA along with increased myeloperoxidase and ornithine decarboxylase activities, suggesting tissue inflammation and cell proliferation. Furthermore, DON (168 nmol) caused enhanced expression of RAS, and phosphorylation of PI3K/Akt, ERK, JNK and p38 MAPKs. DON exposure also showed activation of transcription factors, c-fos, c-jun and NF-κB along with phosphorylation of IkBα. Enhanced phosphorylation of NF-κB by DON caused over expression of target proteins, COX-2, cyclin D1 and iNOS in skin. Though a single topical application of DMBA followed by twice weekly application of DON (84 and 168 nmol) showed no tumorigenesis after 24 weeks, however, histopathological studies suggested hyperplasia of the epidermis and hypertrophy of hair follicles. Interestingly, intestine was also found to be affected as enlarged Peyer's patches were observed, suggesting inflammatory effects which were supported by elevation of inflammatory cytokines after 24 weeks of topical application of DON. These results suggest that DON induced cell proliferation in mouse skin is through the activation of MAPK signaling pathway involving transcription factors NFκB and AP-1, further leading to transcriptional activation of downstream target proteins c-fos, c-jun, cyclin D1, iNOS and COX-2 which might be responsible for its inflammatory potential. - Highlights: • Topical application of DON enhanced epidermal inflammation and cell proliferation. • DON follows PI3K/Akt/MAPK signaling cascade, with activation of AP-1 and NF

  6. Cellular events during scar-free skin regeneration in the spiny mouse, Acomys.

    Science.gov (United States)

    Brant, Jason O; Yoon, Jung H; Polvadore, Trey; Barbazuk, William Brad; Maden, Malcolm

    2016-01-01

    In contrast to the lab mouse, Mus musculus, several species of spiny mouse, Acomys, can regenerate epidermis, dermis, hairs, sebaceous glands with smooth muscle erector pili muscles and skeletal muscle of the panniculus carnonsus after full thickness skin wounding. Here, we have compared the responses of these scarring and nonscarring organisms concentrating on the immune cells and wound cytokines, cell proliferation, and the collagenous components of the wound bed and scar. The blood of Acomys is very neutropenic but there are greater numbers of mast cells in the Acomys wound than the Mus wound. Most importantly there are no F4/80 macrophages in the Acomys wound and many proinflammatory cytokines are either absent or in very low levels which we suggest may be primarily responsible for the excellent regenerative properties of the skin of this species. There is little difference in cell proliferation in the two species either in the epidermis or mesenchymal tissues but the cell density and matrix composition of the wound is very different. In Mus there are 8 collagens which are up-regulated at least 5-fold in the wound creating a strongly trichrome-positive matrix whereas in Acomys there are very few collagens present and the matrix shows only light trichrome staining. The major component of the Mus matrix is collagen XII which is up-regulated between 10 and 30-fold after wounding. These results suggest that in the Acomys wound the absence of many cytokines resulting in the lack of macrophages is responsible for the failure to up-regulate fibrotic collagens, a situation which permits a regenerative response within the skin rather than the generation of a scar.

  7. Antitopoisomerase I monoclonal autoantibodies from scleroderma patients and tight skin mouse interact with similar epitopes.

    Science.gov (United States)

    Muryoi, T; Kasturi, K N; Kafina, M J; Cram, D S; Harrison, L C; Sasaki, T; Bona, C A

    1992-04-01

    We have generated for the first time monoclonal antibodies (mAbs) specific for topoisomerase I (topo I) from scleroderma patients, and tight skin mice which develop a scleroderma-like syndrome. The epitope specificity of these antibodies has been determined using a series of fusion proteins containing contiguous portions of topo I polypeptide. Western blot analysis demonstrated that both human and mouse mAbs bound strongly to fusion protein C encompassing the NH2-terminal portion of the enzyme, and weakly to fusion proteins F and G containing regions close to the COOH-terminal end of the molecule. This crossreactivity is related to a tripeptide sequence homology in F, G, and C fusion proteins. It is interesting that a pentapeptide sequence homologous to that in fusion protein C was identified in the UL70 protein of cytomegalovirus, suggesting that activation of autoreactive B cell clones by molecular mimicry is possible. Both human and mouse mAbs exhibiting the same antigen specificity, also share an interspecies cross-reactive idiotope. These data suggest that B cell clones producing antitopo autoantibodies present in human and mouse repertoire are conserved during phylogeny, and are activated during the development of scleroderma disease.

  8. Study of the mechanisms of flux enhancement through hairless mouse skin by pulsed DC iontophoresis

    Energy Technology Data Exchange (ETDEWEB)

    Pikal, M.J.; Shah, S. (Lilly Research Laboratories, Eli Lilly Co., Indianapolis, IN (USA))

    1991-03-01

    Enhanced iontophoretic transport using pulsed DC is usually explained by citing the observed decrease in skin resistance caused by an increase in AC pulse frequency at very small currents. Alternately, it has been suggested that the on-to-off nature of pulsed DC imparts an impact energy to the fluid, thereby increasing transport. This report provides a test of these mechanisms for enhanced delivery via pulsed iontophoresis. The DC resistance of hairless mouse skin during continuous and pulsed DC iontophoresis is measured as a function of time for selected pulse frequencies and duty cycles using current densities ranging from 0.1 to 1.0 mA/cm2. As a test of the impact energy mechanism, the iontophoretic transport of 14C-glucose measured with pulsed DC is compared with similar data obtained previously using continuous DC. It is suggested that pulsed current can yield lower resistance and enhanced drug delivery provided that (a) the steady-state current during the on phase of the pulse is very small and (b) the frequency is low enough to allow depolarization of the skin during the off phase of the pulse. The glucose transport results suggest that the impact energy concept does not apply to iontophoresis.

  9. Biological and metabolic response in STS-135 space-flown mouse skin.

    Science.gov (United States)

    Mao, X W; Pecaut, M J; Stodieck, L S; Ferguson, V L; Bateman, T A; Bouxsein, M L; Gridley, D S

    2014-08-01

    There is evidence that space flight condition-induced biological damage is associated with increased oxidative stress and extracellular matrix (ECM) remodeling. To explore possible mechanisms, changes in gene expression profiles implicated in oxidative stress and in ECM remodeling in mouse skin were examined after space flight. The metabolic effects of space flight in skin tissues were also characterized. Space Shuttle Atlantis (STS-135) was launched at the Kennedy Space Center on a 13-day mission. Female C57BL/6 mice were flown in the STS-135 using animal enclosure modules (AEMs). Within 3-5 h after landing, the mice were euthanized and skin samples were harvested for gene array analysis and metabolic biochemical assays. Many genes responsible for regulating production and metabolism of reactive oxygen species (ROS) were significantly (p 1.5 compared to AEM control. For ECM profile, several genes encoding matrix and metalloproteinases involved in ECM remodeling were significantly up-/down-regulated following space flight. To characterize the metabolic effects of space flight, global biochemical profiles were evaluated. Of 332 named biochemicals, 19 differed significantly (p space flight skin samples and AEM ground controls, with 12 up-regulated and 7 down-regulated including altered amino acid, carbohydrate metabolism, cell signaling, and transmethylation pathways. Collectively, the data demonstrated that space flight condition leads to a shift in biological and metabolic homeostasis as the consequence of increased regulation in cellular antioxidants, ROS production, and tissue remodeling. This indicates that astronauts may be at increased risk for pathophysiologic damage or carcinogenesis in cutaneous tissue.

  10. Exposure of mouse skin to organic peroxides: subchronic effects related to carcinogenic potential.

    Science.gov (United States)

    Hanausek, Margaret; Walaszek, Zbigniew; Viaje, Aurora; LaBate, Michael; Spears, Erick; Farrell, David; Henrich, Richard; Tveit, Ann; Walborg, Earl F; Slaga, Thomas J

    2004-03-01

    Screening of newly synthesized organic peroxides for tumor initiating/promoting activity would be greatly facilitated if predictive methodologies could be developed using topical exposures shorter than those required for definitive tumor assessment in mouse skin models. Nine organic peroxides [benzoyl peroxide (BZP), di-t-butyl peroxide (DTBP), t-butyl peroxybenzoate (TBPB), p-t-butyl isopropylbenzene hydroperoxide (TBIBHP), cumene hydroperoxide (CHP), dicetyl peroxydicarbonate (DPD), dicumyl peroxide (DCP), methyl ethyl ketone peroxide (MEKP) and O,O-t-butyl-O-(2-ethylhexyl) monoperoxycarbonate (TBEC)] were evaluated for their ability to increase biomarkers of tumor promotion in mouse skin, i.e. sustained epidermal hyperplasia, dermal inflammation and oxidative DNA damage. Evaluations were performed using SENCAR mice exposed topically for 4 weeks. The organic peroxides varied in their effects on these biomarkers. BZP, TBPB and TBIBHP exhibited significant increases in all three biomarkers associated with tumor promoting activity, CHP produced increases only in sustained epidermal hyperplasia and dermal inflammation, MEKP and DCP produced increases only in sustained epidermal hyperplasia and TBEC produced an increase only in dermal inflammation. DTBP and DPD had no effect on the three parameters studied. TBPB and TBIBHP were selected for further examination of their ability to produce mutations in codons 12, 13 and 61 of the c-Ha-ras protooncogene, i.e. those mutations known to be involved in the initiation of mouse skin tumors, because they were the only peroxides to exhibit significant positive results in all assays except the Ha-ras mutation following 4 weeks of exposure. Evaluations were performed using SENCAR mice dosed topically for 8 or 12 weeks in a complete carcinogenesis protocol or 16 weeks in an initiation/promotion protocol using 7,12-dimethylbenz[a]anthracene, urethane, benzo[a]pyrene and N-methyl-N'-nitro-N-nitrosoguanidine as positive controls

  11. Sulforaphane induces phase II detoxication enzymes in mouse skin and prevents mutagenesis induced by a mustard gas analog

    Energy Technology Data Exchange (ETDEWEB)

    Abel, E.L. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States); Boulware, S. [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States); Fields, T.; McIvor, E.; Powell, K.L. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States); DiGiovanni, J.; Vasquez, K.M. [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States); MacLeod, M.C., E-mail: mcmacleod@mdanderson.org [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States)

    2013-02-01

    Mustard gas, used in chemical warfare since 1917, is a mutagenic and carcinogenic agent that produces severe dermal lesions for which there are no effective therapeutics; it is currently seen as a potential terrorist threat to civilian populations. Sulforaphane, found in cruciferous vegetables, is known to induce enzymes that detoxify compounds such as the sulfur mustards that react through electrophilic intermediates. Here, we observe that a single topical treatment with sulforaphane induces mouse epidermal levels of the regulatory subunit of glutamate-cysteine ligase, the rate-limiting enzyme in glutathione biosynthesis, and also increases epidermal levels of reduced glutathione. Furthermore, a glutathione S-transferase, GSTA4, is also induced in mouse skin by sulforaphane. In an in vivo model in which mice are given a single mutagenic application of the sulfur mustard analog 2-(chloroethyl) ethyl sulfide (CEES), we now show that therapeutic treatment with sulforaphane abolishes the CEES-induced increase in mutation frequency in the skin, measured four days after exposure. Sulforaphane, a natural product currently in clinical trials, shows promise as an effective therapeutic against mustard gas. -- Highlights: ► Sulforaphane induces increased levels of glutathione in mouse skin. ► Sulforaphane induces increased levels of GSTA4 in mouse skin. ► Sulforaphane, applied after CEES-treatment, completely abolishes CEES-mutagenesis. ► The therapeutic effect may suggest a long biological half-life for CEES in vivo.

  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

    Energy Technology Data Exchange (ETDEWEB)

    Kundu, Joydeb Kumar [College of Pharmacy, Keimyung University, Daegu 704-701 (Korea, Republic of); Liu, Lijia; Shin, Jun-Wan [Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 151-742 (Korea, Republic of); Surh, Young-Joon, E-mail: surh@plaza.snu.ac.kr [Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 151-742 (Korea, Republic of); Cancer Research Institute, Seoul National University, Seoul 110-799 (Korea, Republic of)

    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.

  13. Effects of oral administration of glucosylceramide on gene expression changes in hairless mouse skin: comparison of whole skin, epidermis, and dermis.

    Science.gov (United States)

    Takatori, Ryo; Le Vu, Phuong; Iwamoto, Taku; Satsu, Hideo; Totsuka, Mamoru; Chida, Kazuhiro; Shimizu, Makoto

    2013-01-01

    The beneficial effects of dietary glucosylceramide on the barrier function of the skin have been increasingly reported, but the entire mechanism has not been clarified. By DNA microarray, we investigated changes in gene expression in hairless mouse skin when a damage-inducing AD diet and a glucosylceramide diet (GluCer) were imposed. GluCer administration potentially suppressed the upregulation of six genes and the downregulation of four genes in the AD group. Examination of the epidermal and/or dermal expression of Npr3, Cyp17a1, Col1a1, S100a9, Sprr2f, Apol7a, Tppp, and Scd3 revealed responses of various parts of the skin to the diets. In normal hairless mice, GluCer administration induced an increase in the dermal expression of Cyp17a1 and the epidermal expression of Tppp, and a decrease in the epidermal expression of S100a9. Our results provide information on gene expression not only in whole skin but also in the epidermis and dermis that should prove useful in the search for the mechanisms underlying the effects of GluCer on damaged and normal skin.

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

    Directory of Open Access Journals (Sweden)

    Yueh-Hsiung Kuo

    2016-09-01

    Full Text Available 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.

  15. Formation of DNA adducts in the skin of psoriasis patients, in human skin in organ culture, and in mouse skin and lung following topical application of coal-tar and juniper tar.

    Science.gov (United States)

    Schoket, B; Horkay, I; Kósa, A; Páldeák, L; Hewer, A; Grover, P L; Phillips, D H

    1990-02-01

    Preparations of coal-tar and juniper tar (cade oil) that are used in the treatment of psoriasis are known to contain numerous potentially carcinogenic polycyclic aromatic hydrocarbons (PAH). Evidence of covalent binding to DNA by components of these mixtures was sought in a) human skin biopsy samples from 12 psoriasis patients receiving therapy with these agents, b) human skin explants maintained in organ culture and treated topically with the tars, and c) the skin and lungs of mice treated with repeated doses of the formulations following the regimen used in the clinic. DNA was isolated from the human and mouse tissues and digested enzymically to mononucleotides. 32P-Post-labeling analysis revealed the presence of aromatic DNA adducts in the biopsy samples at levels of up to 0.4 fmol total adducts/microgram DNA. Treatment of human skin in organ culture produced similar levels of adducts, while treatment with dithranol, a non-mutagenic therapeutic agent, resulted in chromatograms indistinguishable from those from untreated controls. In mouse skin, coal-tar ointment and juniper tar gave similar DNA adduct levels, with a similar time-course of removal: maximum levels (0.5 fmol/microgram DNA) at 24 h after the final treatment declined rapidly to 0.05 fmol/microgram at 7 d, thereafter declining slowly over the succeeding 25 d. However, while coal-tar ointment produced only very low levels of adducts in mouse lung (less than 0.03 fmol/microgram DNA), juniper tar produced adducts at a high level (0.7 fmol/microgram DNA) that were persistent in this tissue. These results provide direct evidence for the formation of potentially carcinogenic DNA damage in human and mouse tissue by components of these therapeutic tar preparations.

  16. Transport behavior of hairless mouse skin during constant current DC iontophoresis I: baseline studies.

    Science.gov (United States)

    Liddell, Mark R; Li, S Kevin; Higuchi, William I

    2011-04-01

    The fluxes of charged and nonionic molecules across hairless mouse skin (HMS) were induced by direct current iontophoresis and used to characterize the transport pathways of the epidermal membrane. Experimental data were used to determine permeability coefficients from which the effective pore radii (Rp) of the transport pathways were calculated. Permeants used in these experiments were nonionic permeants (urea, mannitol, and raffinose), monovalent cationic permeants (sodium, tetraethylammonium, and tetraphenylphosphonium ions), and monovalent anionic permeants (chloride, salicylate, and taurocholate ions). The Rp estimates obtained by the anionic permeant pairs were 49, 22, and 20 Å for the chloride/salicylate (Cl:SA), chloride/taurocholate (Cl:TC), and salicylate/taurocholate (SA:TC) pairs, respectively; with the cationic permeant pairs, the Rp values obtained were 19, 30, and 24 Å for the sodium/tetraethylammonium (Na:TEA), sodium/tetraphenylphosphonium (Na:TPP), and the tetraethylammonium/tetraphenylphosphonium (TEA:TPP) pairs, respectively. Rp estimates for HMS obtained from nonionic permeant experiments ranged from 6.7 to 13.4 Å. When plotted versus their respective diffusion coefficients, all of the permeability coefficients for the cationic permeants were greater than those of the anionic permeants. Additionally, the magnitudes of permeability coefficients determined in the current study with HMS were of the same order of magnitude as those previously determined in our laboratory using human epidermal membrane under similar iontophoresis conditions.

  17. Carcinogenicity and co-carcinogenicity studies on propoxur in mouse skin.

    Science.gov (United States)

    Shukla, Y; Baqar, S M; Mehrotra, N K

    1998-12-01

    Propoxur (2-isopropoxyphenyl methylcarbamate) is a widely used broad spectrum carbamate insecticide mainly used to control household pests. Propoxur exposure is reported to inhibit cholinesterase activity in rodents. Apart from other toxic effects, propoxur was found to possess tumorigenic activity in rats after oral administration. Propoxur does not produce tumours in mice or hamsters, or bladder hyperplasia in dogs and monkeys following oral feeding. In this set of investigations the complete carcinogenic, tumour initiating and promoting potential of propoxur was evaluated in male and female Swiss albino mice, since no information was available following dermal exposure of propoxur. The animals were exposed to propoxur through topical painting on the interscapular region at a dose of 100 mg/kg body weight. The results revealed that propoxur has tumour promoting potential on mouse skin following a two-stage initiation-promotion protocol, but it failed to induce the tumour(s) at a significant level, when tested for tumour initiating and complete carcinogenic property.

  18. Loss of Endogenous Interleukin-12 Activates Survival Signals in Ultraviolet-Exposed Mouse Skin and Skin Tumors

    Directory of Open Access Journals (Sweden)

    Syed M. Meeran

    2009-09-01

    Full Text Available Interleukin-12 (IL-12-deficiency promotes photocarcinogenesis in mice; however, the molecular mechanisms underlying this effect have not been fully elucidated. Here, we report that long-term exposure to ultraviolet (UV radiation resulted in enhancement of the levels of cell survival kinases, such as phosphatidylinositol 3-kinase (PI3K, Akt (Ser473, p-ERK1/2, and p-p38 in the skin of IL-12p40 knockout (IL-12 KO mice compared with the skin of wild-type mice. UV-induced activation of nuclear factor-κB (NF-κB/p65 in the skin of IL-12 KO mice was also more prominent. The levels of NF-κB-targeted proteins, such as proliferating cell nuclear antigen (PCNA, cyclooxygenase-2, cyclin D1, and inducible nitric oxide synthase, were higher in the UV-exposed skin of IL-12 KO mice than the UV-exposed skin of wild types. In short-term UV irradiation experiments, subcutaneous treatment of IL-12 KO mice with recombinant IL-12 (rIL-12 or topical treatment with oridonin, an inhibitor of NF-κB, resulted in the inhibition of UV-induced increases in the levels of PCNA, cyclin D1, and NF-κB compared with non-rIL-12- or non-oridonin-treated IL-12 KO mice. UV-induced skin tumors of IL-12 KO mice had higher levels of PI3K, p-Akt (Ser473, p-ERK1/2, p-p38, NF-κB, and PCNA and fewer apoptotic cells than skin tumors of wild types. Together, these data suggest that the loss of endogenous IL-12 activates survival signals in UV-exposed skin and that may lead to the enhanced photocarcinogenesis in mice.

  19. Genetic ablation of caspase-7 promotes solar-simulated light-induced mouse skin carcinogenesis: the involvement of keratin-17.

    Science.gov (United States)

    Lee, Mee-Hyun; Lim, Do Young; Kim, Myoung Ok; Lee, Sung-Young; Shin, Seung Ho; Kim, Jae Young; Kim, Sung-Hyun; Kim, Dong Joon; Jung, Sung Keun; Yao, Ke; Kundu, Joydeb Kumar; Lee, Hye Suk; Lee, Cheol-Jung; Dickinson, Sally E; Alberts, David; Bowden, G Timothy; Stratton, Steven; Curiel, Clara; Einspahr, Janine; Bode, Ann M; Surh, Young-Joon; Cho, Yong-Yeon; Dong, Zigang

    2015-11-01

    Solar ultraviolet irradiation is an environmental carcinogen that causes skin cancer. Caspase-7 is reportedly expressed at reduced levels in many cancers. The present study was designed to examine the role of caspase-7 in solar-simulated light (SSL)-induced skin cancer and to elucidate its underlying molecular mechanisms. Our study revealed that mice with genetic deficiency of caspase-7 are highly susceptible to SSL-induced skin carcinogenesis. Epidermal hyperplasia, tumor volume and the average number of tumors were significantly increased in caspase-7 knockout (KO) mice compared with SKH1 wild-type mice irradiated with SSL. The expression of cell proliferation markers, such as survivin and Ki-67, was elevated in SSL-irradiated skin of caspase-7 KO mice compared with those observed in SSL-exposed wild-type SKH1 mouse skin. Moreover, SSL-induced apoptosis was abolished in skin from caspase-7 KO mice. Two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/ionization-time-of-flight analysis of skin tissue lysates from SSL-irradiated SKH1 wild-type and caspase-7 KO mice revealed an aberrant induction of keratin-17 in caspase-7 KO mice. Immunohistochemical analysis of skin tumors also showed an increase of keratin-17 expression in caspase-7 KO mice compared with SKH1 wild-type mice. The expression of keratin-17 was also elevated in SSL-irradiated caspase-7 KO keratinocytes as well as in human basal cell carcinomas. The in vitro caspase activity assay showed keratin-17 as a substrate of caspase-7, but not caspase-3. Overall, our study demonstrates that genetic loss of caspase-7 promotes SSL-induced skin carcinogenesis by blocking caspase-7-mediated cleavage of keratin-17.

  20. Severe combined immunodeficiency mouse and human psoriatic skin chimeras. Validation of a new animal model.

    OpenAIRE

    1995-01-01

    Research into the cause and pathophysiological mechanisms underlying expression of psoriatric skin lesions has been hampered by lack of an appropriate animal model for this common and enigmatic cutaneous disease. These studies characterize normal skin, pre-psoriatic skin, and psoriatic plaque skin samples transplanted onto severe combined immunodeficiency mice. In this report we document that 1), normal, prepsoriatic, and psoriatic plaque keratome skin samples can be transplanted onto severe ...

  1. Relevance of the mouse skin initiation-promotion model for the classification of carcinogenic substances encountered at the workplace.

    Science.gov (United States)

    Schwarz, Michael; Thielmann, Heinz W; Meischner, Veronika; Fartasch, Manigé

    2015-06-01

    The Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area (MAK Commission of the Deutsche Forschungsgemeinschaft) evaluates chemical substances using scientific criteria to prevent adverse effects on health at the work place. As part of this task there is a need to evaluate tumor promoting activity of chemicals (enhancement of formation of squamous cell carcinomas via premalignant papillomas) obtained from two-stage initiation/promotion experiments using the mouse skin model. In the present communication we address this issue by comparing responses seen in mouse skin with those in humans. We conclude that tumor promotional effects seen in such animal models be carefully analyzed on a case by case basis. Substances that elicit a rather non-specific effect that is restricted to the high dose range are considered to be irrelevant to humans and thus do not require classification as carcinogens. In contrast, substances that might have both a mode of action and a potency similar to the specific effects seen with TPA (12-O-tetradecanoylphorbol-13-acetate), the prototype tumor promoter in mouse skin, which triggers receptor-mediated signal cascades in the very low dose range, have to be classified in a category for carcinogens.

  2. Gomisin A inhibits tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in two-stage carcinogenesis in mouse skin.

    Science.gov (United States)

    Yasukawa, K; Ikeya, Y; Mitsuhashi, H; Iwasaki, M; Aburada, M; Nakagawa, S; Takeuchi, M; Takido, M

    1992-01-01

    Gomisin A, isolated from the fruits of Schisandra chinensis, is one of the dibenzocyclooctadiene lignans. Application of 12-O-tetradecanoylphorbol-13-acetate (TPA, 1 microgram/ear), a tumor-promoting agent, to the ears of mice induces inflammation. Among seven dibenzocyclooctadiene lignans assayed, gomisin A, gomisin J, and wuweizisu C inhibited the inflammatory activity induced by TPA in mice. The ED50 of these compounds for TPA-induced inflammation was 1.4-4.4 mumol. Gomisin A, with an ED50 of 1.4 mumol, showed the strongest inhibitory effect. Furthermore, at 5 mumol/mouse, it markedly suppressed the promotion effect of TPA (2.5 micrograms/mouse) on skin tumor formation in mice following initiation with 7,12-dimethylbenz[a]anthracene (50 micrograms/mouse). It is assumed that the inhibition of tumor promotion by gomisin A is due to its anti-inflammatory activity.

  3. Cell death induced on cell cultures and nude mouse skin by non-thermal, nanosecond-pulsed generated plasma.

    Directory of Open Access Journals (Sweden)

    Arnaud Duval

    Full Text Available Non-thermal plasmas are gaseous mixtures of molecules, radicals, and excited species with a small proportion of ions and energetic electrons. Non-thermal plasmas can be generated with any high electro-magnetic field. We studied here the pathological effects, and in particular cell death, induced by nanosecond-pulsed high voltage generated plasmas homogeneously applied on cell cultures and nude mouse skin. In vitro, Jurkat cells and HMEC exhibited apoptosis and necrosis, in dose-dependent manner. In vivo, on nude mouse skin, cell death occurred for doses above 113 J/cm(2 for the epidermis, 281 J/cm(2 for the dermis, and 394 J/cm(2 for the hypodermis. Using electron microscopy, we characterized apoptosis for low doses and necrosis for high doses. We demonstrated that these effects were not related to thermal, photonic or pH variations, and were due to the production of free radicals. The ability of cold plasmas to generate apoptosis on cells in suspension and, without any sensitizer, on precise skin areas, opens new fields of application in dermatology for extracorporeal blood cell treatment and the eradication of superficial skin lesions.

  4. Effect of permeation enhancers on the release and permeation kinetics of Lincomycin hydrochloride gel formulations through mouse skin

    Directory of Open Access Journals (Sweden)

    Panigrahi L

    2006-01-01

    Full Text Available Lincomycin hydrochloride is a systemic antibiotic, which is active against most common gram positive bacteria. It has proved to be excellent for infectious diseases like acne, anthrax, pneumonia, and also for the treatment of furunculosis, carbuncles, impetigo, burns and wounds, carrying to gram positive bacteria. Gels were prepared using carbopol 940 as gelling agent, and isopropyl myristate and dimethyl sulfoxide as permeation enhancer. The formulations were evaluated for drug content, viscosity, pH, extrudability, homogeneity, skin irritation test, spreadability, and gel strength. A formulation containing 1.5% carbopol with 10% isopropyl myristate, showed better in vitro skin permeation through abdominal mouse skin, and was found to be the best.

  5. Expression analysis of the mouse S100A7/psoriasin gene in skin inflammation and mammary tumorigenesis

    Directory of Open Access Journals (Sweden)

    Niu Yulian

    2005-02-01

    Full Text Available Abstract Background The human psoriasin (S100A7 gene has been implicated in inflammation and tumor progression. Implementation of a mouse model would facilitate further investigation of its function, however little is known of the murine psoriasin gene. In this study we have cloned the cDNA and characterized the expression of the potential murine ortholog of human S100A7/psoriasin in skin inflammation and mammary tumorigenesis. Methods On the basis of chromosomal location, phylogenetic analysis, amino acid sequence similarity, conservation of a putative Jab1-binding motif, and similarities of the patterns of mouse S100A7/psoriasin gene expression (measured by RT-PCR and in-situ hybridization with those of human S100A7/psoriasin, we propose that mouse S100A7/psoriasin is the murine ortholog of human psoriasin/S100A7. Results Although mouse S100A7/psoriasin is poorly conserved relative to other S100 family members, its pattern of expression parallels that of the human psoriasin gene. In murine skin S100A7/psoriasin was significantly upregulated in relation to inflammation. In murine mammary gland expression is also upregulated in mammary tumors, where it is localized to areas of squamous differentiation. This mirrors the context of expression in human tumor types where both squamous and glandular differentiation occur, including cervical and lung carcinomas. Additionally, mouse S100A7/psoriasin possesses a putative Jab1 binding motif that mediates many downstream functions of the human S100A7 gene. Conclusion These observations and results support the hypothesis that the mouse S100A7 gene is structurally and functionally similar to human S100A7 and may offer a relevant model system for studying its normal biological function and putative role in tumor progression.

  6. Effects of the co-carcinogen catechol on benzo(a)pyrene metabolism and DNA adduct formation in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Melikian, A.A.; Leszczynska, J.M.; Hecht, S.S.; Hoffmann, D.

    1986-01-01

    We have studied the effects of the co-carcinogen catechol (1,2-dihydroxybenzene) on the metabolic activation of (/sup 3/H) benzo(a)pyrene (BaP) in mouse skin, in vivo and on the binding of BaP metabolites to DNA and protein at intervals from 0.5-24 h. Upon topical application of 0.015 mg (/sup 3/H)BaP and 0.25 or 0.5 mg catechol per mouse, catechol had little effect on the total amount of (/sup 3/H)BaP metabolized in mouse skin, but it affected the relative proportions of (/sup 3/H)BaP metabolites. Catechol (0.5 mg/mouse) decreased the proportion of water-soluble (/sup 3/H)BaP metabolites, ethyl acetate-soluble polar metabolites and quinones, but doubled the levels of unconjugated 3-hydroxy-BaP at all measured intervals after treatment. Catechol also caused a small increase in the levels of trans-7,8-dihydroxy-7,8-dihydroBaP and trans-9,10-dihydroxy-9,10-dihydroBaP 0.5 h after treatment. Two hours after treatment, the levels of these metabolites subsided to those of the controls. Catechol did not affect the levels of glutathione conjugates of BaP. However, it caused a decrease in glucuronide and sulphate conjugate formation from BaP. Catechol caused an approximately 2-fold increase in the formation of anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydroBaP (BPDE) DNA adducts and elevated the ratio of anti-syn-BPDE-DNA adducts 1.6 to 2.9-fold. Catechol treatment increased the radioactivity associated with epidermal proteins after (/sup 3/H)BaP application. Because catechol increased levels of 3-hydroxyBaP, we considered the possibility that 3-hydroxyBaP might enhance the tumor initiating activities of BaP or BPDE in mouse skin; a bioassay demonstrated that this was not the case. The results of this study indicate that one important effect of catechol related to its co-carcinogenicity is its ability to enhance formation of anti-BPDE-DNA adducts in mouse skin.

  7. DNA adducts in human and mouse skin maintained in short-term culture and treated with petrol and diesel engine lubricating oils.

    Science.gov (United States)

    Carmichael, P L; Ni Shé, M; Phillips, D H

    1991-05-24

    Human and mouse skin samples maintained in short-term organ culture were treated topically with used engine oils from petrol- and diesel-powered vehicles. Mice were also treated topically in vivo for comparison. DNA was isolated and analysed by 32P-postlabelling and the labeled DNA digests were resolved on polyethyleneimine-cellulose tlc sheets. A large number of radioactive adduct spots were observed in DNA from skin treated with the used petrol-engine oil, indicating the formation of adducts by many components of the complex oil mixture. Total adduct levels were similar in mouse skin (both in vivo and in vitro) and in human skin, although qualitative differences in the adduct maps were apparent between the human and mouse skin DNA. Treatment with the used diesel engine oil produced adduct levels no greater than that of control samples in mouse skin (in vivo and in vitro), although significant levels were found in human skin DNA from one donor. The results correlate well with the carcinogenic activity of these oils in experimental animals, helping to substantiate the conclusion that petrol engine oils (but not diesel engine oils) may present a carcinogenic risk to man if appropriate measures to minimise skin contact are not observed.

  8. C/EBPalpha and C/EBPbeta are required for Sebocyte differentiation and stratified squamous differentiation in adult mouse skin.

    Directory of Open Access Journals (Sweden)

    John S House

    Full Text Available C/EBPalpha and C/EBPbeta are bZIP transcription factors that are highly expressed in the interfollicular epidermis and sebaceous glands of skin and yet germ line deletion of either family member alone has only mild or no effect on keratinocyte biology and their role in sebocyte biology has never been examined. To address possible functional redundancies and reveal functional roles of C/EBPalpha and C/EBPbeta in postnatal skin, mouse models were developed in which either family member could be acutely ablated alone or together in the epidermis and sebaceous glands of adult mice. Acute removal of either C/EBPalpha or C/EBPbeta alone in adult mouse skin revealed modest to no discernable changes in epidermis or sebaceous glands. In contrast, co-ablation of C/EBPalpha and C/EBPbeta in postnatal epidermis resulted in disruption of stratified squamous differentiation characterized by hyperproliferation of basal and suprabasal keratinocytes and a defective basal to spinous keratinocyte transition involving an expanded basal compartment and a diminished and delayed spinous compartment. Acute co-ablation of C/EBPalpha and C/EBPbeta in sebaceous glands resulted in severe morphological defects, and sebocyte differentiation was blocked as determined by lack of sebum production and reduced expression of stearoyl-CoA desaturase (SCD3 and melanocortin 5 receptor (MC5R, two markers of terminal sebocyte differentiation. Specialized sebocytes of Meibomian glands and preputial glands were also affected. Our results indicate that in adult mouse skin, C/EBPalpha and C/EBPbeta are critically involved in regulating sebocyte differentiation and epidermal homeostasis involving the basal to spinous keratinocyte transition and basal cell cycle withdrawal.

  9. Recovery of Aging-Related Size Increase of Skin Epithelial Cells: In vivo Mouse and In vitro Human Study

    Science.gov (United States)

    Sokolov, Igor; Guz, Natali V.; Iyer, Swaminathan; Hewitt, Amy; Sokolov, Nina A.; Erlichman, Joseph S.; Woodworth, Craig D.

    2015-01-01

    The size increase of skin epithelial cells during aging is well-known. Here we demonstrate that treatment of aging cells with cytochalasin B substantially decreases cell size. This decrease was demonstrated on a mouse model and on human skin cells in vitro. Six nude mice were treated by topical application of cytochalasin B on skin of the dorsal left midsection for 140 days (the right side served as control for placebo treatment). An average decrease in cell size of 56±16% resulted. A reduction of cell size was also observed on primary human skin epithelial cells of different in vitro age (passages from 1 to 8). A cell strain obtained from a pool of 6 human subjects was treated with cytochalasin B in vitro for 12 hours. We observed a decrease in cell size that became statistically significant and reached 20–40% for cells of older passage (6–8 passages) whereas no substantial change was observed for younger cells. These results may be important for understanding the aging processes, and for cosmetic treatment of aging skin. PMID:25807526

  10. Effects of skin-derived precursors on wound healing of denervated skin in a nude mouse model.

    Science.gov (United States)

    Shu, Bin; Xie, Ju-Lin; Xu, Ying-Bin; Lai, Wen; Huang, Yong; Mao, Ren-Xiang; Liu, Xu-Sheng; Qi, Shao-Hai

    2015-01-01

    Denervated skin could result in impaired healing of wounds, such as decubitus ulcers and diabetic foot ulcers. Other studies indicated that cutaneous fiber density is reduced after inner nerve transection and that neuropeptide level depletes after denervation, leading to reduced cell proliferation around the wound and thus wound healing problems. Recent studies have revealed that skin-derived precursors (SKPs), which form a neural crest-related stem cell population in the dermis of skin, participate in cutaneous nerve regeneration. We hypothesized that injecting SKPs into denervated wound promotes healing. A bilateral denervation wound model was established followed by SKP transplantation. The wound healing rate was determined at 7, 14, and 21 d after injury. Cell proliferation activity during wound healing was analyzed by proliferating cell nuclear antigen immunohistochemistry (IHC). Nerve fiber density was measured by S-100 IHC. The contents of nerve growth factor, substance P, and calcitonin gene-related peptide were examined by enzyme-linked immunosorbent assay. The rate of epithelization in the SKP-treated group was faster than that in the control group. Wound cell proliferation and nerve fiber density were obviously higher in the SKP-treated group than in the control group. In addition, the content of neuropeptides was higher in the SKP-treated group than in the control group during wound healing. In conclusion, SKPs can promote denervated wound healing through cell proliferation and nerve fiber regeneration, and can facilitate the release of neuropeptides.

  11. Curcumin Stimulates the Antioxidant Mechanisms in Mouse Skin Exposed to Fractionated γ-Irradiation

    OpenAIRE

    Ganesh Chandra Jagetia; Golgod Krishnamurthy Rajanikant

    2015-01-01

    Fractionated irradiation is one of the important radiotherapy regimens to treat different types of neoplasia. Despite of the immense therapeutic gains accrued by delivering fractionated irradiation to tumors, the radiation burden on skin increases significantly. Low doses of irradiation to skin adversely affect its molecular and metabolic status. The use of antioxidant/s may help to alleviate the radiation-induced changes in the skin and allow delivering a higher dose of radiation to attain b...

  12. Severe combined immunodeficiency mouse-psoriatic human skin xenograft model: A modern tool connecting bench to bedside

    Directory of Open Access Journals (Sweden)

    Smriti Kundu-Raychaudhuri

    2014-01-01

    Full Text Available Psoriasis is a multifactorial chronic inflammatory disease. Research into the pathogenesis of this disease is hindered by the lack of a proper animal model. Over the past two decades, many scientists were involved in the development of animal models that nearly mirror the immunopathogenesis of psoriasis. One such model, which has opened doors to the study of molecular complexities of psoriasis as well as its treatment, is the severe combined immunodeficiency (SCID mouse-human skin chimera model. This model not only mirrors the clinical and histopathological features of psoriasis but also help in the study of cell proliferation, angiogenesis, function of T cells, neurogenic inflammation and cytokines involved in inflammatory reactions. In this article, we have reviewed the prospects and the limitations of the SCID mouse model of psoriasis.

  13. Long-term bezafibrate treatment improves skin and spleen phenotypes of the mtDNA mutator mouse.

    Directory of Open Access Journals (Sweden)

    Lloye M Dillon

    Full Text Available Pharmacological agents, such as bezafibrate, that activate peroxisome proliferator-activated receptors (PPARs and PPAR γ coactivator-1α (PGC-1α pathways have been shown to improve mitochondrial function and energy metabolism. The mitochondrial DNA (mtDNA mutator mouse is a mouse model of aging that harbors a proofreading-deficient mtDNA polymerase γ. These mice develop many features of premature aging including hair loss, anemia, osteoporosis, sarcopenia and decreased lifespan. They also have increased mtDNA mutations and marked mitochondrial dysfunction. We found that mutator mice treated with bezafibrate for 8-months had delayed hair loss and improved skin and spleen aging-like phenotypes. Although we observed an increase in markers of fatty acid oxidation in these tissues, we did not detect a generalized increase in mitochondrial markers. On the other hand, there were no improvements in muscle function or lifespan of the mutator mouse, which we attributed to the rodent-specific hepatomegaly associated with fibrate treatment. These results showed that despite its secondary effects in rodent's liver, bezafibrate was able to improve some of the aging phenotypes in the mutator mouse. Because the associated hepatomegaly is not observed in primates, long-term bezafibrate treatment in humans could have beneficial effects on tissues undergoing chronic bioenergetic-related degeneration.

  14. Topical application of nitrosonifedipine, a novel radical scavenger, ameliorates ischemic skin flap necrosis in a mouse model.

    Science.gov (United States)

    Fukunaga, Yutaka; Izawa-Ishizawa, Yuki; Horinouchi, Yuya; Sairyo, Eriko; Ikeda, Yasumasa; Ishizawa, Keisuke; Tsuchiya, Koichiro; Abe, Yoshiro; Hashimoto, Ichiro; Tamaki, Toshiaki

    2017-01-16

    Ischemic skin flap necrosis can occur in random pattern flaps. An excess amount of reactive oxygen species is generated and causes necrosis in the ischemic tissue. Nitrosonifedipine (NO-NIF) has been demonstrated to possess potent radical scavenging ability. However, there has been no study on the effects of NO-NIF on ischemic skin flap necrosis. Therefore, they evaluated the potential of NO-NIF in ameliorating ischemic skin flap necrosis in a mouse model. A random pattern skin flap (1.0 × 3.0 cm) was elevated on the dorsum of C57BL/6 mice. NO-NIF was administered by topical injection immediately after surgery and every 24 hours thereafter. Flap survival was evaluated on postoperative day 7. Tissue samples from the skin flaps were harvested on postoperative days 1 and 3 to analyze oxidative stress, apoptosis and endothelial dysfunction. The viable area of the flap in the NO-NIF group was significantly increased (78.30 ± 7.041%) compared with that of the control group (47.77 ± 6.549%, p NIF reduced oxidative stress, apoptosis and endothelial dysfunction, which were evidenced by the decrease of malondialdehyde, p22phox protein expression, number of apoptotic cells, phosphorylated p38 MAPK protein expression, and vascular cell adhesion molecule-1 protein expression while endothelial nitric oxide synthase protein expression was increased. In conclusion, they demonstrated that NO-NIF ameliorated ischemic skin flap necrosis by reducing oxidative stress, apoptosis, and endothelial dysfunction. NO-NIF is considered to be a candidate for the treatment of ischemic flap necrosis.

  15. Efficient in vivo gene editing using ribonucleoproteins in skin stem cells of recessive dystrophic epidermolysis bullosa mouse model.

    Science.gov (United States)

    Wu, Wenbo; Lu, Zhiwei; Li, Fei; Wang, Wenjie; Qian, Nannan; Duan, Jinzhi; Zhang, Yu; Wang, Fengchao; Chen, Ting

    2017-02-14

    The prokaryotic CRISPR/Cas9 system has recently emerged as a powerful tool for genome editing in mammalian cells with the potential to bring curative therapies to patients with genetic diseases. However, efficient in vivo delivery of this genome editing machinery and indeed the very feasibility of using these techniques in vivo remain challenging for most tissue types. Here, we show that nonreplicable Cas9/sgRNA ribonucleoproteins can be used to correct genetic defects in skin stem cells of postnatal recessive dystrophic epidermolysis bullosa (RDEB) mice. We developed a method to locally deliver Cas9/sgRNA ribonucleoproteins into the skin of postnatal mice. This method results in rapid gene editing in epidermal stem cells. Using this method, we show that Cas9/sgRNA ribonucleoproteins efficiently excise exon80, which covers the point mutation in our RDEB mouse model, and thus restores the correct localization of the collagen VII protein in vivo. The skin blistering phenotype is also significantly ameliorated after treatment. This study provides an in vivo gene correction strategy using ribonucleoproteins as curative treatment for genetic diseases in skin and potentially in other somatic tissues.

  16. Efficient in vivo gene editing using ribonucleoproteins in skin stem cells of recessive dystrophic epidermolysis bullosa mouse model

    Science.gov (United States)

    Wu, Wenbo; Lu, Zhiwei; Li, Fei; Wang, Wenjie; Qian, Nannan; Duan, Jinzhi; Zhang, Yu; Wang, Fengchao; Chen, Ting

    2017-01-01

    The prokaryotic CRISPR/Cas9 system has recently emerged as a powerful tool for genome editing in mammalian cells with the potential to bring curative therapies to patients with genetic diseases. However, efficient in vivo delivery of this genome editing machinery and indeed the very feasibility of using these techniques in vivo remain challenging for most tissue types. Here, we show that nonreplicable Cas9/sgRNA ribonucleoproteins can be used to correct genetic defects in skin stem cells of postnatal recessive dystrophic epidermolysis bullosa (RDEB) mice. We developed a method to locally deliver Cas9/sgRNA ribonucleoproteins into the skin of postnatal mice. This method results in rapid gene editing in epidermal stem cells. Using this method, we show that Cas9/sgRNA ribonucleoproteins efficiently excise exon80, which covers the point mutation in our RDEB mouse model, and thus restores the correct localization of the collagen VII protein in vivo. The skin blistering phenotype is also significantly ameliorated after treatment. This study provides an in vivo gene correction strategy using ribonucleoproteins as curative treatment for genetic diseases in skin and potentially in other somatic tissues. PMID:28137859

  17. Resveratrol and black tea polyphenol combination synergistically suppress mouse skin tumors growth by inhibition of activated MAPKs and p53.

    Directory of Open Access Journals (Sweden)

    Jasmine George

    Full Text Available Cancer chemoprevention by natural dietary agents has received considerable importance because of their cost-effectiveness and wide safety margin. However, single agent intervention has failed to bring the expected outcome in clinical trials; therefore, combinations of chemopreventive agents are gaining increasing popularity. The present study aims to evaluate the combinatorial chemopreventive effects of resveratrol and black tea polyphenol (BTP in suppressing two-stage mouse skin carcinogenesis induced by DMBA and TPA. Resveratrol/BTP alone treatment decreased tumor incidence by ∼67% and ∼75%, while combination of both at low doses synergistically decreased tumor incidence even more significantly by ∼89% (p<0.01. This combination also significantly regressed tumor volume and number (p<0.01. Mechanistic studies revealed that this combinatorial inhibition was associated with decreased expression of phosphorylated mitogen-activated protein kinase family proteins: extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase 1/2, p38 and increased in total p53 and phospho p53 (Ser 15 in skin tissue/tumor. Treatment with combinations of resveratrol and BTP also decreased expression of proliferating cell nuclear antigen in mouse skin tissues/tumors than their solitary treatments as determined by immunohistochemistry. In addition, histological and cell death analysis also confirmed that resveratrol and BTP treatment together inhibits cellular proliferation and markedly induces apoptosis. Taken together, our results for the first time lucidly illustrate that resveratrol and BTP in combination impart better suppressive activity than either of these agents alone and accentuate that development of novel combination therapies/chemoprevention using dietary agents will be more beneficial against cancer. This promising combination should be examined in therapeutic trials of skin and possibly other cancers.

  18. 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.

    Science.gov (United States)

    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.

  19. Coordination by Cdc42 of Actin, Contractility, and Adhesion for Melanoblast Movement in Mouse Skin

    DEFF Research Database (Denmark)

    Woodham, Emma F; Paul, Nikki R; Tyrrell, Benjamin

    2017-01-01

    traverse the dermis to reach the epidermis of the skin and hair follicles. We previously established that Rac1 signals via Scar/WAVE and Arp2/3 to effect pseudopod extension and migration of melanoblasts in skin. Here we show that RhoA is redundant in the melanocyte lineage but that Cdc42 coordinates...

  20. Suppressive Effect of Dietary Fucoidan on Proinflammatory Immune Response and MMP-1 Expression in UVB-Irradiated Mouse Skin.

    Science.gov (United States)

    Maruyama, Hiroko; Tamauchi, Hidekazu; Kawakami, Fumitaka; Yoshinaga, Keiko; Nakano, Takahisa

    2015-10-01

    It is well known that ultraviolet B irradiation leads to dermal inflammation. In this study, we found that Mekabu fucoidan suppressed edema, decreased the thickness of the prickle cell layer, and decreased matrix metalloproteinase 1 in the skin of mice irradiated with ultraviolet B. Moreover, we found that the mean level of interferon gamma of Mekabu fucoidan-treated, ultraviolet B-irradiated mice (approximately 2.2 ng/mL) was not significantly different from that in normal mice (approximately 2.5 ng/mL). In contrast, a significant decrease in the mean level of interferon gamma (approximately 1.3 ng/mL) in ultraviolet B-irradiated control mice was observed compared with that in Mekabu fucoidan-treated, ultraviolet B-irradiated mice. The mean thickness of the prickle cell layer in the skin of Mekabu fucoidan-treated, ultraviolet B-irradiated mice was less than that in the ultraviolet B-irradiated control mice. Metalloproteinase 1 activity was significantly higher in the skin of ultraviolet B-irradiated mice than in the skin of untreated, nonirradiated normal mice. Metalloproteinase 1 in the skin of ultraviolet B-irradiated, Mekabu fucoidan- or L(+)-ascorbic acid (vitamin C)-treated mice was significantly lower than that in the ultraviolet B-irradiated control mice. Mitigation of the morphological changes in Mekabu fucoidan-treated mice was correlated with a decrease in metalloproteinase 1 levels. These data indicate that Mekabu fucoidan is an effective suppressor of inflammation in an ultraviolet B-irradiated mouse model.

  1. Gene Expression Architecture of Mouse Dorsal and Tail Skin Reveals Functional Differences in Inflammation and Cancer

    Directory of Open Access Journals (Sweden)

    David A. Quigley

    2016-07-01

    Full Text Available Inherited germline polymorphisms can cause gene expression levels in normal tissues to differ substantially between individuals. We present an analysis of the genetic architecture of normal adult skin from 470 genetically unique mice, demonstrating the effect of germline variants, skin tissue location, and perturbation by exogenous inflammation or tumorigenesis on gene signaling pathways. Gene networks related to specific cell types and signaling pathways, including sonic hedgehog (Shh, Wnt, Lgr family stem cell markers, and keratins, differed at these tissue sites, suggesting mechanisms for the differential susceptibility of dorsal and tail skin to development of skin diseases and tumorigenesis. The Pten tumor suppressor gene network is rewired in premalignant tumors compared to normal tissue, but this response to perturbation is lost during malignant progression. We present a software package for expression quantitative trait loci (eQTL network analysis and demonstrate how network analysis of whole tissues provides insights into interactions between cell compartments and signaling molecules.

  2. MicroRNA-27a-3p Inhibits Melanogenesis in Mouse Skin Melanocytes by Targeting Wnt3a.

    Science.gov (United States)

    Zhao, Yuanyuan; Wang, Pengchao; Meng, Jinzhu; Ji, Yuankai; Xu, Dongmei; Chen, Tianzhi; Fan, Ruiwen; Yu, Xiuju; Yao, Jianbo; Dong, Changsheng

    2015-05-14

    MicroRNAs (miRNAs) play an essential role in the regulation of almost all the biological processes, including melanogenesis. MiR-27a-3p is nearly six times higher in white alpaca skin compared to brown skin, which indicates that miR-27a-3p may be a candidate regulator for melanogenesis. Wnt3a plays an important role in promoting melanoblasts to differentiate into melanocytes and melanogenesis. To confirm the function of miR-27a-3p to melanogenesis in mammals, miR-27a-3p mimic, inhibitor and their negative control were transfected into mouse melanocytes. As a result, miR-27a-3p inhibits melanogenesis by repressing Wnt3a at post-transcriptional level. A significant decrease in Wnt3a luciferase activity was observed in 293T cells co-transfected with the matched luciferase reporter vector and pre-miR-27a. Furthermore, the presence of exogenous miR-27a-3p significantly decreased Wnt3a protein expression rather than mRNA and reduced β-catenin mRNA levels in melanocytes. The over-expression of miR-27a-3p significantly increased the melanin content of melanocytes. However, miR-27a-3p inhibitor performs an opposite effect on melanogenesis. Wnt3a is one target of miR-27a-3p. MiR-27a-3p could inhibit Wnt3a protein amount by post-transcriptional regulation and melanogenesis in mouse melanocytes. Previous studies reported that Wnt3a promoted melanogenensis in mouse melanocytes. Thus, miR-27-3p inhibits melanogenesis by repressing Wnt3a protein expression.

  3. Deoxynivalenol induced mouse skin tumor initiation: Elucidation of molecular mechanisms in human HaCaT keratinocytes.

    Science.gov (United States)

    Mishra, Sakshi; Tewari, Prachi; Chaudhari, Bhushan P; Dwivedi, Premendra D; Pandey, Haushila P; Das, Mukul

    2016-11-01

    Among food contaminants, mycotoxins are toxic to both human and animal health. Our prior studies suggest that Deoxynivalenol (DON), a mycotoxin, behaves as a tumor promoter by inducing edema, hyperplasia, ODC activity and activation of MAPK's in mouse skin. In this study, topical application of DON, 336 and 672 nmol significantly enhanced ROS levels, DNA damage and apoptosis with concomitant downregulation of Ki-67, cyclin D, cyclin E, cyclin A and cyclin-dependent kinases (CDK4 and CDK2) thereby resulting in tumor initiation in mouse skin. Further, the elucidation of molecular mechanisms of tumor initiation by DON (0.42-3.37 nmol/ml) in HaCaT keratinocytes, revealed (i) enhanced ROS generation with cell cycle phase arrest in G0/G1 phase, (ii) increase in levels of 8-OxoG (6-24 hr) and γH2AX protein, (iii) significant enhancement in oxidative stress marker enzymes LPO, GSH, GR with concomitant decrease in antioxidant enzymes catalase, GPx, GST, SOD and mitochondrial membrane potential after DON (1.68 nmol) treatment, (iv) suppression of Nrf2 translocation to nucleus, enhanced phosphorylation with subsequent activation ERK1/2, p38 and JNK MAPK's following DON (1.68 nmol) treatment, (v) overexpression of c-jun, c-fos proteins, upregulation of Bax along with downregulation of Bcl-2 proteins, (vi) increase in cytochrome-c, caspase-9, caspase-3 and poly ADP ribose polymerase levels leads to apoptosis. Pretreatment of superoxide dismutase, mannitol and ethanol to HaCaT cells resulted in significant reduction in ROS levels and apoptosis indicating the role of superoxide and hydroxyl radicals in DON induced apoptosis as an early event and skin tumor initiation as a late event.

  4. A role for estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) in collagen biosynthesis in mouse skin

    Science.gov (United States)

    Markiewicz, Margaret; Znoyko, Sergey; Stawski, Lukasz; Ghatnekar, Angela; Gilkeson, Gary; Trojanowska, Maria

    2012-01-01

    Hormonal regulation of the dermal collagenous extracellular matrix plays a key role in maintaining proper tissue homeostasis, however the factors and pathways involved in this process are not fully defined. This study investigated the role of estrogen receptors (ERs) in the regulation of collagen biosynthesis in mice lacking ERα or ERβ. Collagen content was significantly increased in the skin of ΕRα-/- mice as measured by acetic acid extraction and the hydroxyproline assay and correlated with the decreased levels of MMP-15 and elevated collagen production by ΕRα-/- fibroblasts. In contrast, collagen content was decreased in the skin of ERβ-/- mice despite markedly increased collagen production by ERβ-/- fibroblasts. However, expression of several matrix metalloproteinases (MMPs), including MMP-8 and -15 was significantly elevated suggesting increased degradation of dermal collagen. Furthermore, ERβ-/- mice were characterized by significantly reduced levels of small leucine proteoglycans (SLRPs), lumican and decorin, leading to the defects in collagen fibrillogenesis and possibly less stable collagen fibrils. ERα-/- mice also exhibited fibrils with irregular structure and size, which correlated with increased levels of lumican and decorin. Together, these results demonstrate distinct functions of estrogen receptors in the regulation of collagen biosynthesis in mouse skin in vivo. PMID:22895361

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

    Science.gov (United States)

    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.

  6. Protection against 12-O-tetradecanoylphorbol-13-acetate-caused inflammation in SENCAR mouse ear skin by polyphenolic fraction isolated from green tea.

    Science.gov (United States)

    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 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 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.

  7. Skin-derived mesenchymal stem cells help restore function to ovaries in a premature ovarian failure mouse model.

    Directory of Open Access Journals (Sweden)

    Dongmei Lai

    Full Text Available Skin-derived mesenchymal stem cells (SMSCs can differentiate into the three embryonic germ layers. For this reason, they are considered a powerful tool for therapeutic cloning and offer new possibilities for tissue therapy. Recent studies showed that skin-derived stem cells can differentiate into cells expressing germ-cell specific markers in vitro and form oocytes in vivo. The idea that SMSCs may be suitable for the treatment of intractable diseases or traumatic tissue damage has attracted attention. To determine the ability of SMSCs to reactivate injured ovaries, a mouse model with ovaries damaged by busulfan and cyclophosphamide was developed and is described here. Female skin-derived mesenchymal stem cells (F-SMSCs and male skin-derived mesenchymal stem cells (M-SMSCs from red fluorescence protein (RFP transgenic adult mice were used to investigate the restorative effects of SMSCs on ovarian function. Significant increases in total body weight and the weight of reproductive organs were observed in the treated animals. Both F-SMSCs and M-SMSCs were shown to be capable of partially restoring fertility in chemotherapy-treated females. Immunostaining with RFP and anti-Müllerian hormone (AMH antibodies demonstrated that the grafted SMSCs survived, migrated to the recipient ovaries. After SMSCs were administered to the treated mice, real-time PCR showed that the expression levels of pro-inflammatory cytokines TNF-α, TGF-β, IL-8, IL-6, IL-1β, and IFNγ were significantly lower in the ovaries than in the untreated controls. Consistent with this observation, expression of oogenesis marker genes Nobox, Nanos3, and Lhx8 increased in ovaries of SMSCs-treated mice. These findings suggest that SMSCs may play a role within the ovarian follicle microenvironment in restoring the function of damaged ovaries and could be useful in reproductive health.

  8. Entactin: ultrastructural localization of an ubiquitous basement membrane glycoprotein in mouse skin

    DEFF Research Database (Denmark)

    Horiguchi, Y; Fine, J D; Ljubimov, A V;

    1989-01-01

    Entactin is a recently described sulfated glycoprotein component of mouse endodermal cell-derived extracellular matrix and is present in a number of basement membranes. It has been ultrastructurally localized to both lamina densa and adjacent epithelial cell membranes in rodent kidney. In the pre...

  9. In Vivo SILAC-Based Proteomics Reveals Phosphoproteome Changes during Mouse Skin Carcinogenesis

    DEFF Research Database (Denmark)

    Zanivan, Sara; Meves, Alexander; Behrendt, Kristina;

    2013-01-01

    SILAC technology in combination with high-resolution mass spectrometry (MS) can be successfully used to measure phosphoproteomes in vivo. Here, Zanivan, Mann, and colleagues have applied SILAC-based MS to investigate phosphoproteomic changes during skin carcinogenesis, using the DMBA/TPA two...

  10. Monitoring changes in the scattering properties of mouse skin with optical coherence tomography during an in vivo glucose tolerance test

    Science.gov (United States)

    Kinnunen, M.; Tausta, S.; Myllylä, R.; Vainio, S.

    2007-05-01

    A non-invasive glucose monitoring technique would make evaluation of blood glucose values easier and more convenient. This would help diabetic patients to control their blood glucose values more regularly. A few years ago optical coherence tomography (OCT) was proposed as a non-invasive sensor for monitoring changes in blood glucose concentration. The method is based on monitoring glucose-induced changes in the scattering properties of the target. This article describes how OCT was used to monitor changes in the scattering properties of mouse skin during an in vivo glucose tolerance test. The results show that OCT has the potential to register glucose-induced changes in the optical properties of the sample. However, a commercial OCT device with a probe designed for imaging is not very suitable for non-invasive monitoring of glucose-induced changes in scattering. The problems confronted in this study, possibly originating from the small size of the animals, are discussed in the article.

  11. Optical Monitoring of Living Nerve Terminal Labeling in Hair Follicle Lanceolate Endings of the Ex Vivo Mouse Ear Skin.

    Science.gov (United States)

    Bewick, Guy S; Banks, Robert W

    2016-04-05

    A novel dissection and recording technique is described for optical monitoring staining and de-staining of lanceolate terminals surrounding hair follicles in the skin of the mouse pinna. The preparation is simple and relatively fast, reliably yielding extensive regions of multiple labeled units of living nerve terminals to study uptake and release of styryl pyridinium dyes extensively used in studies of vesicle recycling. Subdividing the preparations before labeling allows test vs. control comparisons in the same ear from a single individual. Helpful tips are given for improving the quality of the preparation, the labeling and the imaging parameters. This new system is suitable for assaying pharmacologically and mechanically-induced uptake and release of these vital dyes in lanceolate terminals in both wild-type and genetically modified animals. Examples of modulatory influences on labeling intensity are given.

  12. Relative biological effectiveness of carbon ions for tumor control, acute skin damage and late radiation-induced fibrosis in a mouse model

    DEFF Research Database (Denmark)

    Sørensen, Brita Singers; Horsman, Michael Robert; Alsner, Jan;

    2015-01-01

    Background. The aim of the present study was to compare the biological effectiveness of carbon ions relative to x-rays between tumor control, acute skin reaction and late RIF of CDF1 mice. Material and methods. CDF1 mice with a C3H mouse mammary carcinoma implanted subcutaneously on the foot of t...

  13. Hair Follicle Morphogenesis in the Treatment of Mouse Full-Thickness Skin Defects Using Composite Human Acellular Amniotic Membrane and Adipose Derived Mesenchymal Stem Cells

    Science.gov (United States)

    Minjuan, Wu; Jun, Xiong; Shiyun, Shao; Sha, Xu; Haitao, Ni

    2016-01-01

    Early repair of skin injury and maximal restoration of the function and appearance have become important targets of clinical treatment. In the present study, we observed the healing process of skin defects in nude mice and structural characteristics of the new skin after transplantation of isolated and cultured adipose derived mesenchymal stem cells (ADMSCs) onto the human acellular amniotic membrane (AAM). The result showed that ADMSCs were closely attached to the surface of AAM and grew well 24 h after seeding. Comparison of the wound healing rate at days 7, 14, and 28 after transplantation showed that ADMSCs seeded on AAM facilitated the healing of full-thickness skin wounds more effectively as compared with either hAM or AAM alone, indicating that ADMSCs participated in skin regeneration. More importantly, we noticed a phenomenon of hair follicle development during the process of skin repair. Composite ADMSCs and AAM not only promoted the healing of the mouse full-thickness defects but also facilitated generation of the appendages of the affected skin, thus promoting restoration of the skin function. Our results provide a new possible therapy idea for the treatment of skin wounds with respect to both anatomical regeneration and functional restoration. PMID:27597871

  14. Hair Follicle Morphogenesis in the Treatment of Mouse Full-Thickness Skin Defects Using Composite Human Acellular Amniotic Membrane and Adipose Derived Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Wu Minjuan

    2016-01-01

    Full Text Available Early repair of skin injury and maximal restoration of the function and appearance have become important targets of clinical treatment. In the present study, we observed the healing process of skin defects in nude mice and structural characteristics of the new skin after transplantation of isolated and cultured adipose derived mesenchymal stem cells (ADMSCs onto the human acellular amniotic membrane (AAM. The result showed that ADMSCs were closely attached to the surface of AAM and grew well 24 h after seeding. Comparison of the wound healing rate at days 7, 14, and 28 after transplantation showed that ADMSCs seeded on AAM facilitated the healing of full-thickness skin wounds more effectively as compared with either hAM or AAM alone, indicating that ADMSCs participated in skin regeneration. More importantly, we noticed a phenomenon of hair follicle development during the process of skin repair. Composite ADMSCs and AAM not only promoted the healing of the mouse full-thickness defects but also facilitated generation of the appendages of the affected skin, thus promoting restoration of the skin function. Our results provide a new possible therapy idea for the treatment of skin wounds with respect to both anatomical regeneration and functional restoration.

  15. Characterization of Neurofibromas of the Skin and Spinal Roots in a Mouse Model

    Science.gov (United States)

    2011-02-01

    I and J) surrounding fat cells ([I], blue arrows), sebaceous glands ([I], arrows), and hair follicles ([I], arrowheads). Dermal tumors stained more in...respectively target an Nf1 mutation into neural crest stem cells (NCSCs) and more differentiated Schwann cells in mouse sciatic nerves. As shown in Figure...lay the foundation to design novel therapies for neurofibroma prevention and to target neurofibromas at early stages of development. 5 Task 2

  16. YAP regulates the expression of Hoxa1 and Hoxc13 in mouse and human oral and skin epithelial tissues.

    Science.gov (United States)

    Liu, Ming; Zhao, Shuangyun; Lin, Qingjie; Wang, Xiu-Ping

    2015-04-01

    Yes-associated protein (YAP) is a Hippo signaling transcriptional coactivator that plays pivotal roles in stem cell proliferation, organ size control, and tumor development. The downstream targets of YAP have been shown to be highly context dependent. In this study, we used the embryonic mouse tooth germ as a tool to search for the downstream targets of YAP in ectoderm-derived tissues. Yap deficiency in the dental epithelium resulted in a small tooth germ with reduced epithelial cell proliferation. We compared the gene expression profiles of embryonic day 14.5 (E14.5) Yap conditional knockout and YAP transgenic mouse tooth germs using transcriptome sequencing (RNA-Seq) and further confirmed the differentially expressed genes using real-time PCR and in situ hybridization. We found that YAP regulates the expression of Hoxa1 and Hoxc13 in oral and dental epithelial tissues as well as in the epidermis of skin during embryonic and adult stages. Sphere formation assay suggested that Hoxa1 and Hoxc13 are functionally involved in YAP-regulated epithelial progenitor cell proliferation, and chromatin immunoprecipitation (ChIP) assay implies that YAP may regulate Hoxa1 and Hoxc13 expression through TEAD transcription factors. These results provide mechanistic insights into abnormal YAP activities in mice and humans.

  17. Intravital two-photon microscopy of host-pathogen interactions in a mouse model of Staphylococcus aureus skin abscess formation.

    Science.gov (United States)

    Liese, Jan; Rooijakkers, Suzan H M; van Strijp, Jos A G; Novick, Richard P; Dustin, Michael L

    2013-06-01

    Staphylococcus (S.) aureus is a frequent cause of severe skin infections. The ability to control the infection is largely dependent on the rapid recruitment of neutrophils (PMN). To gain more insight into the dynamics of PMN migration and host-pathogen interactions in vivo, we used intravital two-photon (2-P) microscopy to visualize S. aureus skin infections in the mouse. Reporter S. aureus strains expressing fluorescent proteins were developed, which allowed for detection of the bacteria in vivo. By employing LysM-EGFP mice to visualize PMN, we observed the rapid appearance of PMN in the extravascular space of the dermis and their directed movement towards the focus of infection, which led to the delineation of an abscess within 1 day. Moreover, tracking of transferred labelled bone-marrow neutrophils showed that PMN localization to the site of infection is dependent on the presence of G-protein-coupled receptors on the PMN, whereas Interleukin-1 receptor was required on host cells other than PMN. Furthermore, the S. aureus complement inhibitor Ecb could block PMN accumulation at thesite of infection. Our results establish that 2-P microscopy is a powerful tool to investigate the orchestration of the immune cells, S. aureus location and gene expression in vivo on a single cell level.

  18. The effect of ginkgo biloba extract on radiosensitivity of mouse skin and jejunal crypt

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Kyung Hwan; Ha, Sung Whan [Seoul National Univ. Medical College, Seoul (Korea, Republic of)

    1998-06-01

    Ginkgo biloba extract(GBE) is known to increase the peripheral blood circulation. This study was designed to evaluate the effect of GBE on the acute normal tissue radiation reaction. C3H mice were divided into two groups, radiation alone and two doses GBE plus radiation, for both acute skin reaction and jejunal crypt assay. GBE was given i.p. one hour before irradiation with priming dose given one day earlier. Thirty to Fifty Gy for acute skin reaction and 11 to 14 Gy for jejunal crypt were irradiated to right hind leg and whole body, respectively. Radiation doses(RD{sub 50}) for peak skin score of 2.0 were 44.2Gy(40.6-48.2Gy) for radiation alone and 44.4Gy(41.6-47.4Gy) for two doses GBE plus radiation, showing no effect of GBE on acute radiation skin damage. The numbers of regenerating jejunal crypts per circumference were also almost the same for each radiation dose level(p=0.57-0.94), and the mean lethal doses(D{sub o}) were 1.80Gy(1.57-2.09Gy) for radiation alone and 1.88Gy(1.65-2.18Gy) for two doses GBE plus radiation, indicating no effect of GBE on jejunal crypt cell survival after radiation. GBE doesn't increase acute normal tissue radiation reaction in this model system. As GBE was verified to enhance radiation effect on tumor, high therapeutic gain is expected when GBE is combined with radiation therapy.

  19. Dye-enhanced multimodal confocal microscopy for noninvasive detection of skin cancers in mouse models

    Science.gov (United States)

    Park, Jesung; Mroz, Pawel; Hamblin, Michael R.; Yaroslavsky, Anna N.

    2010-03-01

    Skin cancer is the most common form of human cancer. Its early diagnosis and timely treatment is of paramount importance for dermatology and surgical oncology. In this study, we evaluate the use of reflectance and fluorescence confocal microscopy for detecting skin cancers in an in-vivo trial with B16F10 melanoma and SCCVII squamous cell carcinoma in mice. For the experiments, the mice are anesthetized, then the tumors are infiltrated with aqueous solution of methylene blue and imaged. Reflectance images are acquired at 658 nm. Fluorescence is excited at 658 nm and registered in the range between 690 and 710 nm. After imaging, the mice are sacrificed. The tumors are excised and processed for hematoxylin and eosin histopathology, which is compared to the optical images. The results of the study indicate that in-vivo reflectance images provide valuable information on vascularization of the tumor, whereas the fluorescence images mimic the structural features seen in histopathology. Simultaneous dye-enhanced reflectance and fluorescence confocal microscopy shows promise for the detection, demarcation, and noninvasive monitoring of skin cancer development.

  20. The regularity of sustained firing reveals two populations of slowly adapting touch receptors in mouse hairy skin.

    Science.gov (United States)

    Wellnitz, Scott A; Lesniak, Daine R; Gerling, Gregory J; Lumpkin, Ellen A

    2010-06-01

    Touch is initiated by diverse somatosensory afferents that innervate the skin. The ability to manipulate and classify receptor subtypes is prerequisite for elucidating sensory mechanisms. Merkel cell-neurite complexes, which distinguish shapes and textures, are experimentally tractable mammalian touch receptors that mediate slowly adapting type I (SAI) responses. The assessment of SAI function in mutant mice has been hindered because previous studies did not distinguish SAI responses from slowly adapting type II (SAII) responses, which are thought to arise from different end organs, such as Ruffini endings. Thus we sought methods to discriminate these afferent types. We developed an epidermis-up ex vivo skin-nerve chamber to record action potentials from afferents while imaging Merkel cells in intact receptive fields. Using model-based cluster analysis, we found that two types of slowly adapting receptors were readily distinguished based on the regularity of touch-evoked firing patterns. We identified these clusters as SAI (coefficient of variation = 0.78 +/- 0.09) and SAII responses (0.21 +/- 0.09). The identity of SAI afferents was confirmed by recording from transgenic mice with green fluorescent protein-expressing Merkel cells. SAI receptive fields always contained fluorescent Merkel cells (n = 10), whereas SAII receptive fields lacked these cells (n = 5). Consistent with reports from other vertebrates, mouse SAI and SAII responses arise from afferents exhibiting similar conduction velocities, receptive field sizes, mechanical thresholds, and firing rates. These results demonstrate that mice, like other vertebrates, have two classes of slowly adapting light-touch receptors, identify a simple method to distinguish these populations, and extend the utility of skin-nerve recordings for genetic dissection of touch receptor mechanisms.

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

    Science.gov (United States)

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

    2012-03-01

    Strains of mice vary in their susceptibility to ultra-violet (UV) radiation-induced skin tumors. Some strains of hairless mice (homozygous for the spontaneous Hr(hr) 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.

  2. Protective effects of sodium-L-ascorbyl-2 phosphate on the development of UVB-induced damage in cultured mouse skin.

    Science.gov (United States)

    Nayama, S; Takehana, M; Kanke, M; Itoh, S; Ogata, E; Kobayashi, S

    1999-12-01

    The protective effect of sodium-L-ascorbyl-2 phosphate (As-2P), a stable form of ascorbic acid (AsA), against photodamage induced by a single dose of UVB exposure (290-320 nm, Max 312 nm) was investigated using cultured mouse skin. When the cultured skin was treated with various As-2P concentrations, the cutaneous AsA level increased in proportion to the As-2P concentration. After 3 h of incubation, the AsA level in the cultured skin treated with 2, 20 and 100 mM As-2P increased 1.03-, 2.17- and 6.27-fold, respectively, compared with that of the control skin. These results suggest that As-2P was transported into the cultured mouse skin where it was converted to AsA. After 3 h, the cutaneous AsA level in irradiated (20 kJ/m2) skin was depleted to a half of that in the control skin. However, the level in skin pretreated with 20 mM As-2P was maintained within normal limits, even after 24 h. Pretreatment with 20 mM As-2P significantly prevented such photodamage as sunburn cell formation, DNA fragmentation and lipid peroxidation, which were caused by a single dose of UVB irradiation. These results suggest that the protective effect of 20 mM As-2P on UVB-induced cutaneous damage is due to the maintenance of a normal As level by conversion of As-2P to As in skin tissue.

  3. Inhibition of Akt Enhances the Chemopreventive Effects of Topical Rapamycin in Mouse Skin.

    Science.gov (United States)

    Dickinson, Sally E; Janda, Jaroslav; Criswell, Jane; Blohm-Mangone, Karen; Olson, Erik R; Liu, Zhonglin; Barber, Christy; Petricoin, Emanuel F; Calvert, Valerie S; Einspahr, Janine; Dickinson, Jesse E; Stratton, Steven P; Curiel-Lewandrowski, Clara; Saboda, Kathylynn; Hu, Chengcheng; Bode, Ann M; Dong, Zigang; Alberts, David S; Timothy Bowden, G

    2016-03-01

    The PI3Kinase/Akt/mTOR pathway has important roles in cancer development for multiple tumor types, including UV-induced nonmelanoma skin cancer. Immunosuppressed populations are at increased risk of aggressive cutaneous squamous cell carcinoma (SCC). Individuals who are treated with rapamycin (sirolimus, a classical mTOR inhibitor) have significantly decreased rates of developing new cutaneous SCCs compared with those that receive traditional immunosuppression. However, systemic rapamycin use can lead to significant adverse events. Here, we explored the use of topical rapamycin as a chemopreventive agent in the context of solar-simulated light (SSL)-induced skin carcinogenesis. In SKH-1 mice, topical rapamycin treatment decreased tumor yields when applied after completion of 15 weeks of SSL exposure compared with controls. However, applying rapamycin during SSL exposure for 15 weeks, and continuing for 10 weeks after UV treatment, increased tumor yields. We also examined whether a combinatorial approach might result in more significant tumor suppression by rapamycin. We validated that rapamycin causes increased Akt (S473) phosphorylation in the epidermis after SSL, and show for the first time that this dysregulation can be inhibited in vivo by a selective PDK1/Akt inhibitor, PHT-427. Combining rapamycin with PHT-427 on tumor prone skin additively caused a significant reduction of tumor multiplicity compared with vehicle controls. Our findings indicate that patients taking rapamycin should avoid sun exposure, and that combining topical mTOR inhibitors and Akt inhibitors may be a viable chemoprevention option for individuals at high risk for cutaneous SCC.

  4. Inhibition of akt enhances the chemopreventive effects of topical rapamycin in mouse skin

    Science.gov (United States)

    Dickinson, Sally E; Janda, Jaroslav; Criswell, Jane; Blohm-Mangone, Karen; Olson, Erik R.; Liu, Zhonglin; Barber, Christie; Rusche, Jadrian J.; Petricoin, Emmanuel; Calvert, Valerie; Einspahr, Janine G.; Dickinson, Jesse; Stratton, Steven P.; Curiel-Lewandrowski, Clara; Saboda, Kathylynn; Hu, Chengcheng; Bode, Ann M.; Dong, Zigang; Alberts, David S.; Bowden, G. Timothy

    2016-01-01

    The PI3Kinase/Akt/mTOR pathway has important roles in cancer development for multiple tumor types, including UV-induced non-melanoma skin cancer. Immunosuppressed populations are at increased risk of aggressive cutaneous squamous cell carcinoma (SCC). Individuals who are treated with rapamycin, (sirolimus, a classical mTOR inhibitor) have significantly decreased rates of developing new cutaneous SCCs compared to those that receive traditional immunosuppression. However, systemic rapamycin use can lead to significant adverse events. Here we explored the use of topical rapamycin as a chemopreventive agent in the context of solar simulated light (SSL)-induced skin carcinogenesis. In SKH-1 mice, topical rapamycin treatment decreased tumor yields when applied after completion of 15 weeks of SSL exposure compared to controls. However, applying rapamycin during SSL exposure for 15 weeks, and continuing for 10 weeks after UV treatment, increased tumor yields. We also examined whether a combinatorial approach might result in more significant tumor suppression by rapamycin. We validated that rapamycin causes increased Akt (S473) phosphorylation in the epidermis after SSL, and show for the first time that this dysregulation can be inhibited in vivo by a selective PDK1/Akt inhibitor, PHT-427. Combining rapamycin with PHT-427 on tumor prone skin additively caused a significant reduction of tumor multiplicity compared to vehicle controls. Our findings indicate that patients taking rapamycin should avoid sun exposure, and that combining topical mTOR inhibitors and Akt inhibitors may be a viable chemoprevention option for individuals at high risk for cutaneous SCC.

  5. Effect of glycyrrhizin on pseudomonal skin infections in human-mouse chimeras.

    Directory of Open Access Journals (Sweden)

    Shohei Yoshida

    Full Text Available In our previous studies, peripheral blood lineage(-CD34(+CD31(+ cells (CD31(+ IMC appearing in severely burned patients have been characterized as inhibitor cells for the production of β-defensins (HBDs by human epidermal keratinocytes (NHEK. In this study, the effect of glycyrrhizin on pseudomonal skin infections was studied in a chimera model of thermal injury. Two different chimera models were utilized. Patient chimeras were created in murine antimicrobial peptide-depleted NOD-SCID IL-2rγ(null mice that were grafted with unburned skin tissues of severely burned patients and inoculated with the same patient peripheral blood CD31(+ IMC. Patient chimera substitutes were created in the same mice that were grafted with NHEK and inoculated with experimentally induced CD31(+ IMC. In the results, both groups of chimeras treated with glycyrrhizin resisted a 20 LD50 dose of P. aeruginosa skin infection, while all chimeras in both groups treated with saline died within 3 days of the infection. Human antimicrobial peptides were detected from the grafted site tissues of both groups of chimeras treated with glycyrrhizin, while the peptides were not detected in the same area tissues of controls. HBD-1 was produced by keratinocytes in transwell-cultures performed with CD31(+ IMC and glycyrrhizin. Also, inhibitors (IL-10 and CCL2 of HBD-1 production by keratinocytes were not detected in cultures of patient CD31(+ IMC treated with glycyrrhizin. These results indicate that sepsis stemming from pseudomonal grafted site infections in a chimera model of burn injury is controllable by glycyrrhizin. Impaired antimicrobial peptide production at the infection site of severely burned patients may be restored after treatment with glycyrrhizin.

  6. Targeted deletion of Crif1 in mouse epidermis impairs skin homeostasis and hair morphogenesis

    Science.gov (United States)

    Shin, Jung-Min; Choi, Dae-Kyoung; Sohn, Kyung-Cheol; Kim, Ji-Young; Im, Myung; Lee, Young; Seo, Young-Joon; Shong, Minho; Lee, Jeung-Hoon; Kim, Chang Deok

    2017-01-01

    The epidermis, which consists mainly of keratinocytes, acts as a physical barrier to infections by regulating keratinocyte proliferation and differentiation. Hair follicles undergo continuous cycling to produce new one. Therefore, optimum supply of energy from the mitochondria is essential for maintaining skin homeostasis and hair growth. CRIF1 is a mitochondrial protein that regulates mitoribosome-mediated synthesis and insertion of mitochondrial oxidative phosphorylation polypeptides into the mitochondrial membrane in mammals. Recent studies reveal that conditional knockout (cKO) of Crif1 in specific tissues of mice induced mitochondrial dysfunction. To determine whether the mitochondrial function of keratinocytes affects skin homeostasis and hair morphogenesis, we generated epidermis-specific Crif1 cKO mice. Deletion of Crif1 in epidermis resulted in impaired mitochondrial function and Crif1 cKO mice died within a week. Keratinocyte proliferation and differentiation were markedly inhibited in Crif1 cKO mice. Furthermore, hair follicle morphogenesis of Crif1 cKO mice was disrupted by down-regulation of Wnt/β-catenin signaling. These results demonstrate that mitochondrial function in keratinocytes is essential for maintaining epidermal homeostasis and hair follicle morphogenesis. PMID:28317864

  7. Solar-UV-signature mutation prefers TCG to CCG: extrapolative consideration from UVA1-induced mutation spectra in mouse skin.

    Science.gov (United States)

    Ikehata, Hironobu; Kumagai, Jun; Ono, Tetsuya; Morita, Akimichi

    2013-08-01

    UVA1 exerts its genotoxicity on mammalian skin by producing cyclobutane pyrimidine dimers (CPDs) in DNA and preferentially inducing solar-UV-signature mutations, C → T base substitution mutations at methylated CpG-associated dipyrimidine (Py-mCpG) sites, as demonstrated previously using a 364 nm laser as a UVA1 source and lacZ-transgenic mice that utilize the transgene as a mutational reporter. In the present study, we confirmed that a broadband UVA1 source induced the same mutation profiles in mouse epidermis as the UVA1 laser, generalizing the previous result from a single 364 nm to a wider wavelength range of UVA1 (340-400 nm). Combined with our previous data on the mutation spectra induced in mouse epidermis by UVB, UVA2 and solar UVR, we proved that the solar-UV-signature mutation is commonly observed in the wavelength range from UVB to UVA, and found that UVA1 induces this mutation more preferentially than the other shorter wavelength ranges. This finding indicates that the solar-UV-signature mutation-causing CPDs, which are known to prefer Py-mCpG sites, could be produced with the energy provided by the longer wavelength region of UVR, suggesting a photochemical reaction through the excitation of pyrimidine bases to energy states that can be accomplished by absorption of even low-energy UVR. On the other hand, the lower proportions of solar-UV-signature mutations observed in the mutation spectra for UVB and solar UVR indicate that the direct photochemical reaction through excited singlet state of pyrimidine bases, which can be accomplished only by high-energy UVR, is also involved in the mutation induction at those shorter wavelengths of UVR. We also found that the solar-UV signature prefers 5'-TCG-3' to 5'-CCG-3' as mutational target sites, consistent with the fact that UVA induces CPDs selectively at thymine-containing dipyrimidine sites and that solar UVR induces them preferably at Py-mCpG sites. However, the mutation spectrum in human p53 gene from non

  8. Assessment of reinforced poly(ethylene glycol) chitosan hydrogels as dressings in a mouse skin wound defect model

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Szu-Hsien [Institute of Polymer Science and Engineering, College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei City 10617, Taiwan (China); Tsao, Ching-Ting [Institute of Polymer Science and Engineering, College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei City 10617, Taiwan (China); Epithelial Biology Laboratory/Transgenic Mice Core-Laboratory, Department of Anatomy, Chang Gung University, Taoyuan 33302, Taiwan (China); Chang, Chih-Hao [Department of Orthopedics, National Taiwan University Hospital, Taiwan (China); National Taiwan University College of Medicine, No. 1, Jen-Ai Road, Taipei City 10018, Taiwan (China); Lai, Yi-Ting [Department of Chemical Engineering, College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei City 10617, Taiwan (China); Wu, Ming-Fung [Animal Medicine Center, College of Medicine, National Taiwan University, No. 1, Jen-Ai Road, Taipei City 10018, Taiwan (China); Chuang, Ching-Nan [Institute of Polymer Science and Engineering, College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei City 10617, Taiwan (China); Chou, Hung-Chia [Department of Chemical Engineering, College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei City 10617, Taiwan (China); Wang, Chih-Kuang, E-mail: ckwang@kmu.edu.tw [Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 80708, Taiwan (China); Hsieh, Kuo-Haung, E-mail: khhsieh@ntu.edu.tw [Institute of Polymer Science and Engineering, College of Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei City 10617, Taiwan (China)

    2013-07-01

    Wound dressings of chitosan are biocompatible, biodegradable, antibacterial and hemostatic biomaterials. However, applications for chitosan are limited due to its poor mechanical properties. Here, we conducted an in vivo mouse angiogenesis study on reinforced poly(ethylene glycol) (PEG)-chitosan (RPC) hydrogels. RPC hydrogels were formed by cross-linking chitosan with PEGs of different molecular weights at various PEG to chitosan ratios in our previous paper. These dressings can keep the wound moist, had good gas exchange capacity, and was capable of absorbing or removing the wound exudate. We examined the ability of these RPC hydrogels and neat chitosan to heal small cuts and full-thickness skin defects on the backs of male Balb/c mice. Histological examination revealed that chitosan suppressed the infiltration of inflammatory cells and accelerated fibroblast proliferation, while PEG enhanced epithelial migration. The RPC hydrogels promoted wound healing in the small cuts and full layer wounds. The optimal RPC hydrogel had a swelling ratio of 100% and a water vapor transmission rate (WVTR) of about 2000 g/m{sup 2}/day. In addition, they possess good mechanical property and appropriate degradation rates. Thus, the optimal RPC hydrogel formulation functioned effectively as a wound dressing and promoted wound healing. Highlights: ► Mouse angiogenesis study on reinforced poly(ethylene glycol)-chitosan (RPC) ► Water vapor transmission rate of about 2000 g/m{sup 2}/day is characteristic of RPC. ► RPC suppressed inflammatory cells and accelerated fibroblast proliferation. ► RPC composed of 1000-RP10C90 can be used as a biomaterial for wound dressing.

  9. Skin vaccination against cervical cancer associated human papillomavirus with a novel micro-projection array in a mouse model.

    Directory of Open Access Journals (Sweden)

    Holly J Corbett

    Full Text Available BACKGROUND: Better delivery systems are needed for routinely used vaccines, to improve vaccine uptake. Many vaccines contain alum or alum based adjuvants. Here we investigate a novel dry-coated densely-packed micro-projection array skin patch (Nanopatch™ as an alternate delivery system to intramuscular injection for delivering an alum adjuvanted human papillomavirus (HPV vaccine (Gardasil® commonly used as a prophylactic vaccine against cervical cancer. METHODOLOGY/PRINCIPAL FINDINGS: Micro-projection arrays dry-coated with vaccine material (Gardasil® delivered to C57BL/6 mouse ear skin released vaccine within 5 minutes. To assess vaccine immunogenicity, doses of corresponding to HPV-16 component of the vaccine between 0.43 ± 0.084 ng and 300 ± 120 ng (mean ± SD were administered to mice at day 0 and day 14. A dose of 55 ± 6.0 ng delivered intracutaneously by micro-projection array was sufficient to produce a maximal virus neutralizing serum antibody response at day 28 post vaccination. Neutralizing antibody titres were sustained out to 16 weeks post vaccination, and, for comparable doses of vaccine, somewhat higher titres were observed with intracutaneous patch delivery than with intramuscular delivery with the needle and syringe at this time point. CONCLUSIONS/SIGNIFICANCE: Use of dry micro-projection arrays (Nanopatch™ has the potential to overcome the need for a vaccine cold chain for common vaccines currently delivered by needle and syringe, and to reduce risk of needle-stick injury and vaccine avoidance due to the fear of the needle especially among children.

  10. Anti-Skin-Aging Effect of Epigallocatechin Gallate by Regulating Epidermal Growth Factor Receptor Pathway on Aging Mouse Model Induced by D-Galactose.

    Science.gov (United States)

    Chen, Jiming; Li, Yifan; Zhu, Qiangqiang; Li, Tong; Lu, Hao; Wei, Nan; Huang, Yewei; Shi, Ruoyu; Ma, Xiao; Wang, Xuanjun; Sheng, Jun

    2017-03-23

    Epigallocatechin gallate(EGCG) is a monomer separated from tea catechins, as an well-known antioxidant, which helps fight wrinkles and rejuvenate skin cells. In this study, we investigated the anti-aging effect of EGCG, and to clarify underlying mechanism of skin aging in a D-galactose-induced aging mouse model. Forty-five male mice were divided into 5 groups and treated with different dose of EGCG, Vitamin C (VitC) to mice as a positive control. All groups except vehicle were established aging model induced by D-galactose (200mg/kg/day) that was subcutaneously injected to mice for 8 weeks. Two weeks after injection of D-galactose, EGCG and Vit C groups were simultaneously administered once a day by subcutaneously inject after 5hours for injecting D-galactose. The results show that EGCG can be absorbed by the skin. Overall, the conditions of the skin of EGCG-treatment groups were improved, the whole structure of skin were better than control groups, and the levels of oxidative stress and the expression of relate with EGFR proteins were significantly higher than control group after EGCG treatment. All these findings suggest that EGCG can resist skin senility effectively. And the EGFR with relate of downstream proteins are implicated in the skin aging.

  11. Increased Skin Tumor Incidence and Keratinocyte Hyper-Proliferation in a Mouse Model of Down Syndrome.

    Science.gov (United States)

    Yang, Annan; Currier, Duane; Poitras, Jennifer L; Reeves, Roger H

    2016-01-01

    Down syndrome (DS) is a genetic disorder caused by the presence of an extra copy of human chromosome 21 (Hsa21). People with DS display multiple clinical traits as a result of the dosage imbalance of several hundred genes. While many outcomes of trisomy are deleterious, epidemiological studies have shown a significant risk reduction for most solid tumors in DS. Reduced tumor incidence has also been demonstrated in functional studies using trisomic DS mouse models. Therefore, it was interesting to find that Ts1Rhr trisomic mice developed more papillomas than did their euploid littermates in a DMBA-TPA chemical carcinogenesis paradigm. Papillomas in Ts1Rhr mice also proliferated faster. The increased proliferation was likely caused by a stronger response of trisomy to TPA induction. Treatment with TPA caused hyperkeratosis to a greater degree in Ts1Rhr mice than in euploid, reminiscent of hyperkeratosis seen in people with DS. Cultured trisomic keratinocytes also showed increased TPA-induced proliferation compared to euploid controls. These outcomes suggest that altered gene expression in trisomy could elevate a proliferation signalling pathway. Gene expression analysis of cultured keratinocytes revealed upregulation of several trisomic and disomic genes may contribute to this hyperproliferation. The contributions of these genes to hyper-proliferation were further validated in a siRNA knockdown experiment. The unexpected findings reported here add a new aspect to our understanding of tumorigenesis with clinical implications for DS and demonstrates the complexity of the tumor repression phenotype in this frequent condition.

  12. Riboflavin as adjuvant with cisplatin: study in mouse skin cancer model.

    Science.gov (United States)

    Salman, Maria; Naseem, Imrana

    2015-01-01

    Cisplatin used in treatment of solid tumor induces oxidative stress which leads to hepatotoxicity and nephrotoxicity. New strategies are therefore needed to combat toxicity and optimize its therapeutic potential. Riboflavin (VitaminB2) under photoillumination works as an anti proliferative agent and induces apoptosis. These properties of riboflavin have been exploited to mitigate cisplatin induced toxicities. 9,10-dimethylbenz(a)anthracene /12-O-tetradecanoylphorbol-13-acetate  were used to induce skin tumor in Swiss albino mice. The tumor induced mice were treated with cisplatin, riboflavin as well as their combination under photo illumination. In comparison to tumor control group the cisplatin and riboflavin treated groups showed a compromised level of antioxidant enzymes, functional markers and a higher degree of lipid peroxidation. However these parameters tended towards normal in the combination treated group. The results from histopathology indicate that apoptosis was favored mode of cell death and that necrosis was reduced in combination treated groups. Our findings indicate that combination of cisplatin with riboflavin under photo illumination synergizes its anti cancer activity towards cancer cells and attenuates the cisplatin induced toxicities.

  13. Assessment of reinforced poly(ethylene glycol) chitosan hydrogels as dressings in a mouse skin wound defect model.

    Science.gov (United States)

    Chen, Szu-Hsien; Tsao, Ching-Ting; Chang, Chih-Hao; Lai, Yi-Ting; Wu, Ming-Fung; Chuang, Ching-Nan; Chou, Hung-Chia; Wang, Chih-Kuang; Hsieh, Kuo-Haung

    2013-07-01

    Wound dressings of chitosan are biocompatible, biodegradable, antibacterial and hemostatic biomaterials. However, applications for chitosan are limited due to its poor mechanical properties. Here, we conducted an in vivo mouse angiogenesis study on reinforced poly(ethylene glycol) (PEG)-chitosan (RPC) hydrogels. RPC hydrogels were formed by cross-linking chitosan with PEGs of different molecular weights at various PEG to chitosan ratios in our previous paper. These dressings can keep the wound moist, had good gas exchange capacity, and was capable of absorbing or removing the wound exudate. We examined the ability of these RPC hydrogels and neat chitosan to heal small cuts and full-thickness skin defects on the backs of male Balb/c mice. Histological examination revealed that chitosan suppressed the infiltration of inflammatory cells and accelerated fibroblast proliferation, while PEG enhanced epithelial migration. The RPC hydrogels promoted wound healing in the small cuts and full layer wounds. The optimal RPC hydrogel had a swelling ratio of 100% and a water vapor transmission rate (WVTR) of about 2000 g/m(2)/day. In addition, they possess good mechanical property and appropriate degradation rates. Thus, the optimal RPC hydrogel formulation functioned effectively as a wound dressing and promoted wound healing.

  14. Overexpression of galectin-7 in mouse epidermis leads to loss of cell junctions and defective skin repair.

    Directory of Open Access Journals (Sweden)

    Gaëlle Gendronneau

    Full Text Available The proteins of the galectin family are implicated in many cellular processes, including cell interactions, polarity, intracellular trafficking, and signal transduction. In human and mouse, galectin-7 is almost exclusively expressed in stratified epithelia, notably in the epidermis. Galectin-7 expression is also altered in several human tumors of epithelial origin. This study aimed at dissecting the consequences of galectin-7 overexpression on epidermis structure and functions in vivo.We established transgenic mice specifically overexpressing galectin-7 in the basal epidermal keratinocytes and analyzed the consequences on untreated skin and after UVB irradiation or mechanical injury.The intercellular cohesion of the epidermis is impaired in transgenic animals, with gaps developing between adjacent keratinocytes, associated with loss of adherens junctions. The epidermal architecture is aberrant with perturbations in the multilayered cellular organisation of the tissue, and structural defects in the basement membrane. These transgenic animals displayed a reduced re-epithelialisation potential following superficial wound, due to a defective collective migration of keratinocytes. Finally, a single mild dose of UVB induced an abnormal apoptotic response in the transgenic epidermis.These results indicate that an excess of galectin-7 leads to a destabilisation of adherens junctions associated with defects in epidermal repair. As this phenotype shares similarities with that of galectin-7 null mutant mice, we conclude that a critical level of this protein is required for maintaining proper epidermal homeostasis. This study brings new insight into the mode of action of galectins in normal and pathological situations.

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

    Science.gov (United States)

    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.

  16. Effects of type and amount of dietary fat on mouse skin tumor promotion.

    Science.gov (United States)

    Lo, H H; Locniskar, M F; Bechtel, D; Fischer, S M

    1994-01-01

    In a previous study (Cancer Res 51, 907, 1991) in which we found an inverse relationship between quantity of dietary corn oil and saturated fat, in a constant 15% fat diet, on the tumor promotion stage of skin carcinogenesis, it was not clear whether one or both types of fat played a modulatory role. The purpose of the present study therefore was to compare the effect of 1) increasing corn oil in corn oil-only diets and 2) increasing saturated fat, with a constant level of 5% corn oil, on tumor promotion. In the first study, the effects of five levels of dietary corn oil (5%, 10%, 15%, 20%, and 25%) on the incidence and rat of papilloma and carcinoma development were determined in female Sencar mice fed these diets one week after initiation with 7,12-dimethylbenz[a]anthracene and three weeks before the start of promotion with 12-O-tetradecanoylphorbol-13-acetate. A papilloma incidence of 100% was reached first in the 5% corn oil group, at 10 weeks, followed by the 10% group at 13 weeks and the 15% and 20% group at 16 weeks. The highest corn oil group achieved a 90% incidence. There were marked differences in latency of carcinoma development among the diet groups. At Week 29, the cumulative carcinoma incidence was 56% and 32%, respectively, in the 5% and 10% corn oil groups, whereas the incidence in the two highest corn oil (20% and 25%) groups was only 8% and 4%, respectively. In the second study, the effects of diets containing 5% corn oil and increasing levels of coconut oil (5%, 10%, 15%, and 20%) on the incidence and rat of papilloma and carcinoma development were determined, as described above. No significant difference in latency or incidence of papillomas or carcinomas was noted among these saturated fat diet groups. It thus appears that higher levels of dietary corn oil are associated with a reduced cancer incidence in this model system.

  17. 2,6-Dithiopurine, a nucleophilic scavenger, protects against mutagenesis in mouse skin treated in vivo with 2-(chloroethyl) ethyl sulfide, a mustard gas analog

    Energy Technology Data Exchange (ETDEWEB)

    Boulware, Stephen [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States); Fields, Tammy; McIvor, Elizabeth; Powell, K. Leslie; Abel, Erika L. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States); Vasquez, Karen M. [Division of Pharmacy and Toxicology, College of Pharmacy, The University of Texas at Austin, Dell Pediatric Research Institute, 1400 Barbara Jordan Blvd., Austin, TX 78723 (United States); MacLeod, Michael C., E-mail: mcmacleod@mdanderson.org [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Science Park, Smithville, TX 78957 (United States)

    2012-09-01

    Sulfur mustard [bis(2-chloroethyl)sulfide, SM] is a well-known DNA-damaging agent that has been used in chemical warfare since World War I, and is a weapon that could potentially be used in a terrorist attack on a civilian population. Dermal exposure to high concentrations of SM produces severe, long-lasting burns. Topical exposure to high concentrations of 2-(chloroethyl) ethyl sulfide (CEES), a monofunctional analog of SM, also produces severe skin lesions in mice. Utilizing a genetically engineered mouse strain, Big Blue, that allows measurement of mutation frequencies in mouse tissues, we now show that topical treatment with much lower concentrations of CEES induces significant dose- and time-dependent increases in mutation frequency in mouse skin; the mutagenic exposures produce minimal toxicity as determined by standard histopathology and immunohistochemical analysis for cytokeratin 6 and the DNA-damage induced phosphorylation of histone H2AX (γ-H2AX). We attempted to develop a therapeutic that would inhibit the CEES-induced increase in mutation frequency in the skin. We observe that multi-dose, topical treatment with 2,6-dithiopurine (DTP), a known chemical scavenger of CEES, beginning 1 h post-exposure to CEES, completely abolishes the CEES-induced increase in mutation frequency. These findings suggest the possibility that DTP, previously shown to be non-toxic in mice, may be useful as a therapeutic agent in accidental or malicious human exposures to SM. -- Highlights: ► 200 mM 2-(chloroethyl) ethyl sulfide (CEES) induces mutations in mouse skin. ► This dose of CEES is not overtly toxic, as assayed by histopathology. ► 2,6-Dithiopurine (DTP), applied after CEES-treatment, abolishes CEES-mutagenesis. ► This supports the idea that sulfur mustards exhibit long biological half-lives.

  18. Elastase 2 is expressed in human and mouse epidermis and impairs skin barrier function in Netherton syndrome through filaggrin and lipid misprocessing.

    Science.gov (United States)

    Bonnart, Chrystelle; Deraison, Céline; Lacroix, Matthieu; Uchida, Yoshikazu; Besson, Céline; Robin, Aurélie; Briot, Anaïs; Gonthier, Marie; Lamant, Laurence; Dubus, Pierre; Monsarrat, Bernard; Hovnanian, Alain

    2010-03-01

    The human epidermis serves 2 crucial barrier functions: it protects against water loss and prevents penetration of infectious agents and allergens. The physiology of the epidermis is maintained by a balance of protease and antiprotease activities, as illustrated by the rare genetic skin disease Netherton syndrome (NS), in which impaired inhibition of serine proteases causes severe skin erythema and scaling. Here, utilizing mass spectrometry, we have identified elastase 2 (ELA2), which we believe to be a new epidermal protease that is specifically expressed in the most differentiated layer of living human and mouse epidermis. ELA2 localized to keratohyalin granules, where it was found to directly participate in (pro-)filaggrin processing. Consistent with the observation that ELA2 was hyperactive in skin from NS patients, transgenic mice overexpressing ELA2 in the granular layer of the epidermis displayed abnormal (pro-)filaggrin processing and impaired lipid lamellae structure, which are both observed in NS patients. These anomalies led to dehydration, implicating ELA2 in the skin barrier defect seen in NS patients. Thus, our work identifies ELA2 as a major new epidermal protease involved in essential pathways for skin barrier function. These results highlight the importance of the control of epidermal protease activity in skin homeostasis and designate ELA2 as a major protease driving the pathogenesis of NS.

  19. Temporal aspects of tumorigenic response to individual and mixed carcinogens. Comprehensive progress report, June 1, 1975--May 31, 1978. [Mouse skin, rats, hamsters

    Energy Technology Data Exchange (ETDEWEB)

    Albert, R.E.; Burns, F.J.; Altshuler, B.

    1978-02-01

    The research proposed here is designed to obtain a better understanding of the temporal kinetics of tumor induction when one or more carcinogens are present simultaneously or sequentially for prolonged periods of time. Studies done to date under this contract have shown that carcinogenesis in mouse skin by polycyclic aromatic hydrocarbon carcinogens is consistent with the induction of dependent and autonomous cell transformations by the carcinogen followed by the conversion of autonomous tumor cells into malignancies at a rate which is determined by the level of carcinogen exposure. Dependent cell transformations remain latent in the skin unless expressed by a promoting agent. Dependent neoplasia appears to follow one-hit kinetics while malignancy is a multihit endpoint. Dose-related and time-related aspects of tumor induction are separable in the initiation-promotion system of mouse skin which along with rat skin and hamster lung is being used as a model for testing hypotheses. Results to date provide the basis for a new interpretation of the linear non-threshold extrapolation model. The broad aim of the study is to provide a basis or rationale for estimating risks associated with prolonged exposures to carcinogens found in the environment and to predict how different tissues and species respond to the same carcinogens.

  20. Prostaglandin receptor EP2 is responsible for cyclooxygenase-2 induction by prostaglandin E2 in mouse skin.

    Science.gov (United States)

    Ansari, Kausar M; Sung, You Me; He, Guobin; Fischer, Susan M

    2007-10-01

    The EP2 prostanoid receptor is one of the four subtypes of receptors for prostaglandin E2 (PGE2). We previously reported that deletion of EP2 led to resistance to chemically induced mouse skin carcinogenesis, whereas overexpression of EP2 resulted in enhanced tumor development. The purpose of this study was to investigate the underlying molecular mechanisms. We found that EP2 knockout mice had reduced cyclooxygenase-2 (COX-2) expression after 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment compared with wild-type (WT) mice. Further, primary keratinocytes from EP2 transgenic mice had increased COX-2 expression after either TPA or PGE2 treatment and COX-2 expression was blocked by 10 microM SQ 22,536, an adenylate cyclase inhibitor. EP2 knockout mice had significantly decreased, whereas EP2 transgenic mice had significantly increased PGE2 production in response to a single treatment of TPA. Cyclic AMP response element-binding protein (CREB) phosphorylation was elevated to a greater extent in keratinocytes from EP2 transgenic mice compared with those of WT mice following PGE2 treatment. A protein kinase A (PKA) inhibitor reduced PGE2-mediated CREB phosphorylation in keratinocytes from EP2 transgenic mice. Furthermore, we found that there was no CREB phosphorylation in EP2 knockout mice following PGE2 treatment. PGE2-induced DNA synthesis (cell proliferation) was significantly decreased in keratinocytes from EP2 knockout mice following pretreatment with 10 microM SQ 22,536. Taken together, EP2 activation of the PKA/CREB-signaling pathway is responsible for keratinocyte proliferation and our findings reveal a positive feedback loop between COX-2 and PGE2 that is mediated by the EP2 receptor.

  1. Activation-induced cytidine deaminase is dispensable for virus-mediated liver and skin tumor development in mouse models.

    Science.gov (United States)

    Nguyen, Tung; Xu, Jianliang; Chikuma, Shunsuke; Hiai, Hiroshi; Kinoshita, Kazuo; Moriya, Kyoji; Koike, Kazuhiko; Marcuzzi, Gian Paolo; Pfister, Herbert; Honjo, Tasuku; Kobayashi, Maki

    2014-07-01

    Activation-induced cytidine deaminase (AID) not only promotes immune diversity by initiating somatic hypermutation and class switch recombination in immunoglobulin genes but also provokes genomic instability by introducing translocations and mutations into non-immunoglobulin genes. To test whether AID is essential for virus-induced tumor development, we used two transgenic tumor models: mice expressing hepatitis C virus (HCV) core proteins (HCV-Tg), driven by the hepatitis B virus promoter, and mice expressing human papillomavirus type 8 proteins (HPV8-Tg), driven by the Keratin 14 promoter. Both strains were analyzed in the absence and presence of AID by crossing each with AID (-/-) mice. There was no difference in the liver tumor frequency between the HCV-Tg/AID (+/+) and HCV-Tg/AID (-/-) mice at 20 months of age although the AID (+/+) mice showed more severe histological findings and increased cytokine expression. Furthermore, a low level of AID transcript was detected in the HCV-Tg/AID (+/+) liver tissue that was not derived from hepatocytes themselves but from intra-hepatic immune cells. Although AID may not be the direct cause of HCV-induced oncogenesis, AID expressed in B cells, not in hepatocytes, may prolong steatosis and cause increased lymphocyte infiltration into HCV core protein-induced liver lesions. Similarly, there was no difference in the time course of skin tumor development between the HPV8-Tg/AID (-/-) and HPV8-Tg/AID (+/+) groups. In conclusion, AID does not appear to be required for tumor development in the two virus-induced tumor mouse models tested although AID expressed in infiltrating B cells may promote inflammatory reactions in HCV core protein-induced liver pathogenesis.

  2. Effect of orally administered collagen hydrolysate on gene expression profiles in mouse skin: a DNA microarray analysis.

    Science.gov (United States)

    Oba, Chisato; Ito, Kyoko; Ichikawa, Satomi; Morifuji, Masashi; Nakai, Yuji; Ishijima, Tomoko; Abe, Keiko; Kawahata, Keiko

    2015-08-01

    Dietary collagen hydrolysate has been hypothesized to improve skin barrier function. To investigate the effect of long-term collagen hydrolysate administration on the skin, we evaluated stratum corneum water content and skin elasticity in intrinsically aged mice. Female hairless mice were fed a control diet or a collagen hydrolysate-containing diet for 12 wk. Stratum corneum water content and skin elasticity were gradually decreased in chronologically aged control mice. Intake of collagen hydrolysate significantly suppressed such changes. Moreover, we used DNA microarrays to analyze gene expression in the skin of mice that had been administered collagen hydrolysate. Twelve weeks after the start of collagen intake, no significant differences appeared in the gene expression profile compared with the control group. However, 1 wk after administration, 135 genes were upregulated and 448 genes were downregulated in the collagen group. This suggests that gene changes preceded changes of barrier function and elasticity. We focused on several genes correlated with functional changes in the skin. Gene Ontology terms related to epidermal cell development were significantly enriched in upregulated genes. These skin function-related genes had properties that facilitate epidermal production and differentiation while suppressing dermal degradation. In conclusion, our results suggest that altered gene expression at the early stages after collagen administration affects skin barrier function and mechanical properties. Long-term oral intake of collagen hydrolysate improves skin dysfunction by regulating genes related to production and maintenance of skin tissue.

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

    Energy Technology Data Exchange (ETDEWEB)

    Matsuura-Hachiya, Yuko; Arai, Koji Y.; Ozeki, Rieko; Kikuta, Ayako; Nishiyama, Toshio, E-mail: toshio_n@cc.tuat.ac.jp

    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.

  4. Nordihydroguaiaretic Acid from Creosote Bush (Larrea tridentata Mitigates 12-O-Tetradecanoylphorbol-13-Acetate-Induced Inflammatory and Oxidative Stress Responses of Tumor Promotion Cascade in Mouse Skin

    Directory of Open Access Journals (Sweden)

    Shakilur Rahman

    2011-01-01

    Full Text Available Nordihydroguaiaretic acid (NDGA is a phenolic antioxidant found in the leaves and twigs of the evergreen desert shrub, Larrea tridentata (Sesse and Moc. ex DC Coville (creosote bush. It has a long history of traditional medicinal use by the Native Americans and Mexicans. The modulatory effects of topically applied NDGA was studied on acute inflammatory and oxidative stress responses in mouse skin induced by stage I tumor promoting agent, 12-O-tetradecanoylphorbol-13-acetate (TPA. Double TPA treatment adversely altered many of the marker responses of stage I skin tumor promotion cascade. Pretreatment of NDGA in TPA-treated mice mitigated cutaneous lipid peroxidation and inhibited production of hydrogen peroxide. NDGA treatment also restored reduced glutathione level and activities of antioxidant enzymes. Elevated activities of myeloperoxidase, xanthine oxidase and skin edema formation in TPA-treated mice were also lowered by NDGA indicating a restrained inflammatory response. Furthermore, results of histological study demonstrated inhibitory effect of NDGA on cellular inflammatory responses. This study provides a direct evidence of antioxidative and anti-inflammatory properties of NDGA against TPA-induced cutaneous inflammation and oxidative stress corroborating its chemopreventive potential against skin cancer.

  5. Nordihydroguaiaretic Acid from Creosote Bush (Larrea tridentata) Mitigates 12-O-Tetradecanoylphorbol-13-Acetate-Induced Inflammatory and Oxidative Stress Responses of Tumor Promotion Cascade in Mouse Skin.

    Science.gov (United States)

    Rahman, Shakilur; Ansari, Rizwan Ahmed; Rehman, Hasibur; Parvez, Suhel; Raisuddin, Sheikh

    2011-01-01

    Nordihydroguaiaretic acid (NDGA) is a phenolic antioxidant found in the leaves and twigs of the evergreen desert shrub, Larrea tridentata (Sesse and Moc. ex DC) Coville (creosote bush). It has a long history of traditional medicinal use by the Native Americans and Mexicans. The modulatory effects of topically applied NDGA was studied on acute inflammatory and oxidative stress responses in mouse skin induced by stage I tumor promoting agent, 12-O-tetradecanoylphorbol-13-acetate (TPA). Double TPA treatment adversely altered many of the marker responses of stage I skin tumor promotion cascade. Pretreatment of NDGA in TPA-treated mice mitigated cutaneous lipid peroxidation and inhibited production of hydrogen peroxide. NDGA treatment also restored reduced glutathione level and activities of antioxidant enzymes. Elevated activities of myeloperoxidase, xanthine oxidase and skin edema formation in TPA-treated mice were also lowered by NDGA indicating a restrained inflammatory response. Furthermore, results of histological study demonstrated inhibitory effect of NDGA on cellular inflammatory responses. This study provides a direct evidence of antioxidative and anti-inflammatory properties of NDGA against TPA-induced cutaneous inflammation and oxidative stress corroborating its chemopreventive potential against skin cancer.

  6. Overexpression of constitutively active BMP-receptor-IB in mouse skin causes an ichthyosis-vulgaris-like disease.

    Science.gov (United States)

    Yu, Xueyan; Espinoza-Lewis, Ramón A; Sun, Cheng; Lin, Lisong; He, Fenglei; Xiong, Wei; Yang, Jing; Wang, Alun; Chen, Yiping

    2010-12-01

    The skin is the outer layer of protection against the environment. The development and formation of the skin is regulated by several genetic cascades including the bone morphogenetic protein (BMP) signaling pathway, which has been suggested to play an important role during embryonic organ development. Several skin defects and diseases are caused by genetic mutations or disorders. Ichthyosis is a common genetic skin disorder characterized by dry scaly skin. Loss-of-function mutations in the filaggrin (FLG) gene have been identified as the cause of the ichthyosis vulgaris (IV) phenotype; however, the direct regulation of filaggrin expression in vivo is unknown. We present evidence that BMP signaling regulates filaggrin expression in the epidermis. Mice expressing a constitutively active form of BMP-receptor-IB in the developing epidermis exhibit a phenotype resembling IV in humans, including dry flaky skin, compact hyperkeratosis, and an attenuated granular layer associated with a significantly downregulated expression of filaggrin. Regulation of filaggrin expression by BMP signaling has been further confirmed by the application of exogenous BMP2 in skin explants and by a transgenic model overexpressing Noggin in the epidermis. Our results demonstrate that aberrant BMP signaling in the epidermis causes overproliferation and hyperkeratinization, leading to an IV-like skin disease.

  7. Gene Expression Architecture of Mouse Dorsal and Tail Skin Reveals Functional Differences in Inflammation and Cancer | Office of Cancer Genomics

    Science.gov (United States)

    Inherited germline polymorphisms can cause gene expression levels in normal tissues to differ substantially between individuals. We present an analysis of the genetic architecture of normal adult skin from 470 genetically unique mice, demonstrating the effect of germline variants, skin tissue location, and perturbation by exogenous inflammation or tumorigenesis on gene signaling pathways.

  8. Daily intake of Jeju groundwater improves the skin condition of the model mouse for human atopic dermatitis.

    Science.gov (United States)

    Tanaka, Akane; Jung, Kyungsook; Matsuda, Akira; Jang, Hyosun; Kajiwara, Naoki; Amagai, Yosuke; Oida, Kumiko; Ahn, Ginnae; Ohmori, Keitaro; Kang, Kyung-goo; Matsuda, Hiroshi

    2013-03-01

    Drinking water is an important nutrient for human health. The mineral ingredients included in drinking water may affect the physical condition of people. Various kinds of natural water are in circulation as bottled water in developed countries; however, its influence on clinical conditions of patients with certain diseases has not been fully evaluated. In this study, effects of the natural groundwater from Jeju Island on clinical symptoms and skin barrier function in atopic dermatitis (AD) were evaluated. NC/Tnd mice, a model for human AD, with moderate to severe dermatitis were used. Mice were given different natural groundwater or tap water for 8 weeks from 4 weeks of age. Clinical skin severity scores were recorded every week. Scratching analysis and measurement of transepidermal water loss were performed every other week. The pathological condition of the dorsal skin was evaluated histologically. Real-time polymerase chain reaction analysis was performed for cytokine expression in the affected skin. The epidermal hyperplasia and allergic inflammation were reduced in atopic mice supplied with Jeju groundwater when compared to those supplied with tap water or other kinds of natural groundwater. The increase in scratching behavior with the aggravation of clinical severity of dermatitis was favorably controlled. Moreover, transepidermal water loss that reflects skin barrier function was recovered. The early inflammation and hypersensitivity in the atopic skin was alleviated in mice supplied with Jeju groundwater, suggesting its profitable potential on the daily care of patients with skin troubles including AD.

  9. Sarcophine-Diol, a Skin Cancer Chemopreventive Agent, Inhibits Proliferation and Stimulates Apoptosis in Mouse Melanoma B16F10 Cell Line

    Directory of Open Access Journals (Sweden)

    Hesham Fahmy

    2011-12-01

    Full Text Available Sarcodiol (SD is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B16F10 cell line. In this study we report that SD inhibits the de novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the antitumor effect of SD on melanoma cell viability using several biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription protein (STAT-3 and cyclin D1, an activator of cyclin-dependent kinase 4 (Cdk4. SD treatment also enhances cellular level of tumor suppressor protein 53 (p53 and stimulates cleavage of the nuclear poly (ADP-ribose polymerase (cleaved-PARP. SD also enhances cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in melanoma B16F10 tumor cells.

  10. Sarcophine-diol, a skin cancer chemopreventive agent, inhibits proliferation and stimulates apoptosis in mouse melanoma B₁₆F₁₀ cell line.

    Science.gov (United States)

    Szymanski, Pawel T; Kuppast, Bhimanna; Ahmed, Safwat A; Khalifa, Sherief; Fahmy, Hesham

    2012-01-01

    Sarcodiol (SD) is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B₁₆F₁₀ cell line. In this study we report that SD inhibits the de novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the antitumor effect of SD on melanoma cell viability using several biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription protein (STAT-3) and cyclin D1, an activator of cyclin-dependent kinase 4 (Cdk4). SD treatment also enhances cellular level of tumor suppressor protein 53 (p53) and stimulates cleavage of the nuclear poly (ADP-ribose) polymerase (cleaved-PARP). SD also enhances cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis) via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in melanoma B₁₆F₁₀ tumor cells.

  11. Chemopreventive effect of resveratrol, sesamol, sesame oil and sunflower oil in the Epstein-Barr virus early antigen activation assay and the mouse skin two-stage carcinogenesis.

    Science.gov (United States)

    Kapadia, Govind J; Azuine, Magnus A; Tokuda, Harukuni; Takasaki, Midori; Mukainaka, Teruo; Konoshima, Takao; Nishino, Hoyoku

    2002-06-01

    Resveratrol, sesamol, sesame oil and sunflower oil are known natural dietary components with intrinsic cancer chemopreventive potentials. As a part of our study of dietary constituents as potential cancer chemopreventive agents, we have assessed the anti-cancer potentials of these products in the promotion stage of cancer development employing the in vitro Epstein-Barr virus early antigen activation assay induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, we studied the activities of these compounds in the brine shrimp cytotoxicity assay as well as on the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging bioassay with a view to comparing some of the mechanisms of their anti-cancer activity. Finally, we compared the observed chemoprotective capabilities of the four products in the in vivo 7,12 dimethylbenz(a)anthracene initiated and TPA-promoted mouse skin two-stage carcinogenesis protocols. All the products tested showed a profound inhibitory effect on the Epstein-Barr virus early antigen induction using Raji cells. Comparatively, sesame oil was the most potent followed by sesamol and then resveratrol. Only sesamol and resveratrol showed a remarkable cytotoxic activity in the brine shrimp lethality assays as well as profound free radical scavenging activity in the DPPH bioassay. In both test systems, sesamol exhibited a more remarkable activity than resveratrol while sesame oil and sunflower oil did not exhibit any appreciable activity even at the highest concentrations tested (4000 microg ml(-1) ). In our in vivo assay at a 50-fold molar ratio to TPA, sesamol offered 50% reduction in mouse skin papillomas at 20 weeks after promotion with TPA. Under an identical molar ratio to TPA, resveratrol offered a 60% reduction in the papillomas in mouse at 20 weeks. Thus sesamol seems to be an almost equally potent chemopreventive agent. Sesame oil and sunflower oil offered 20 and 40% protection, respectively, in the mouse

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

    Science.gov (United States)

    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.

  13. In Vivo Spectrum of UVC-induced Mutation in Mouse Skin Epidermis May Reflect the Cytosine Deamination Propensity of Cyclobutane Pyrimidine Dimers.

    Science.gov (United States)

    Ikehata, Hironobu; Mori, Toshio; Yamamoto, Masayuki

    2015-11-01

    Although ultraviolet radiation (UVR) has a genotoxicity for inducing skin cancers, the skin may tolerate UVC component because the epidermal layer prevents this short wavelength range from passing through. Here, UVC genotoxicity for mouse skin was evaluated in terms of DNA damage formation and mutagenicity. UVC induced UVR photolesions and mutations remarkably in the epidermis but poorly in the dermis, confirming the barrier ability of the epidermis against shorter UVR wavelengths. Moreover, the epidermis itself responded to UVC mutagenicity with mutation induction suppression, which suppressed the mutant frequencies to a remarkably low, constant level regardless of UVC dose. The mutation spectrum observed in UVC-exposed epidermis showed a predominance of UV-signature mutation, which occurred frequently in 5'-TCG-3', 5'-TCA-3' and 5'-CCA-3' contexts. Especially, for the former two contexts, the mutations recurred at several sites with more remarkable recurrences at the 5'-TCG-3' sites. Comparison of the UVC mutation spectrum with those observed in longer UVR wavelength ranges led us to a mechanism that explains why the sequence context preference of UV-signature mutation changes according to the wavelength, which is based on the difference in the mCpG preference of cyclobutane pyrimidine dimer (CPD) formation among UVR ranges and the sequence context-dependent cytosine deamination propensity of CPD.

  14. Chemical Characterization and Toxicologic Evaluation of Airborne Mixtures. Tumorigenicity Studies of Diesel Fuel-2, Red Smoke Dye and Violet Smoke Dyes in the SENCAR Mouse Skin Tumorigenesis Bioassay System

    Science.gov (United States)

    1985-09-01

    nitrosamides, sulfonates, sultones, and ureas. The 32 chemicals listed in Table 1 include such well known chemical carcino- gens as aflatoxin BI, bis...direct or indirect carcinogen at a subthreshold dose and is essentially irreversible. The promotion phase requires repetitive treatments after...34by initiators of mouse skin tumorigenesis. Cancer Res. 29: 510-514. Hennings, H., B. Michael, and E. Patterson. 1978. Croton oil enhancement of skin

  15. Anti-aging effect of adipose-derived stem cells in a mouse model of skin aging induced by D-galactose.

    Directory of Open Access Journals (Sweden)

    Shengchang Zhang

    Full Text Available INTRODUCTION: Glycation products accumulate during aging of slowly renewing tissue, including skin, and are suggested as an important mechanism underlying the skin aging process. Adipose-derived cells are widely used in the clinic to treat ischemic diseases and enhance wound healing. Interestingly, adipose-derived stem cells (ASCs are also effective in anti-aging therapy, although the mechanism underlying their effects remains unknown. The purpose of the present study was to examine the anti-aging effect of ASCs in a D-galactose-induced aging animal model and to clarify the underlying mechanism. MATERIALS AND METHODS: Six-week-old nude mice were subcutaneously injected with D-gal daily for 8 weeks. Two weeks after completion of treatment, mice were randomized to receive subcutaneous injections of 106 green fluorescent protein (GFP-expressing ASCs, aminoguanidine (AG or phosphate-buffered saline (PBS. Control mice received no treatment. We examined tissue histology and determined the activity of senescence-associated molecular markers such as superoxide dismutase (SOD and malondialdehyde (MDA. RESULTS: Transplanted ASCs were detectable for 14 days and their GFP signal disappeared at day 28 after injection. ASCs inhibited advanced glycation end product (AGE levels in our animal model as well as increased the SOD level and decreased the MDA level, all of which act to reverse the aging phenotype in a similar way to AG, an inhibitor of AGE formation. Furthermore, ASCs released angiogenic factors in vivo such as vascular endothelial growth factor, suggesting a skin trophic effect. CONCLUSIONS: These results demonstrate that ASCs may contribute to the regeneration of skin during aging. In addition, the data shows that ASCs provide a functional benefit by glycation suppression, antioxidation, and trophic effects in a mouse model of aging.

  16. Tumor initiating activities of various derivatives of benz(a)anthracene and 7, 12-dimethyl-benz(a)anthracene in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Slaga, T.J.; Gleason, G.L.; DiGiovanni, J.; Berry, D.L.; Juchau, M.R.; Harvey, R.G.

    1978-01-01

    Current information indicates that polycyclic aromatic hydrocarbons (PAH) exert their toxic, mutagenic, and carcinogenic activities after they have been metabolically activated by target cells to reactive epoxides. The results obtained from IN VIVO and IN VITRO binding, mutagenicity, metabolism, and carcinogenicity studies have led to the conclusion that BP-7, 8-diol is a proximate carcinogenic metabolite of BP, and the BP-diol-epoxide is an ultimate carcinogenic metabolite of BP. Recent results concerning the strong carcinogenicity of BP-7..beta.., 8..cap alpha..-diol-9..cap alpha..,10..cap alpha..-epoxide in newborn mice and in mouse skin strongly indicate that it is the ultimate carcinogenic metabolite of BP. Since diol-epoxides may be responsible for the carcinogenicity of PAH other than BP, diols and diol-epoxides as well as other derivatives of PAH were tested for skin tumor-initiation in a two-stage system of tumorigenesis. In addition, since activation of methylated PAH may involve the side-chain methyl group, the skin tumor-initiating activity of various side-chain derivatives of methylated PA were determined. In this report, the skin tumor initiation of various derivatives of a nonmethylated PAH, BA as well as a methylated PAH, DMBA are compared. The data suggest that bay region diol-epoxides may be important in BA and DMBA carcinogenicity in mice which is supportive of the theory proposed by Jerina and co-workers which predicts that diol-epoxides in the bay region are the major determinants of PAH carcinogenicity.

  17. The effects of Origanum hypericifolium essential oil application and ultraviolet B irradiation on mouse skin: An ultrastructural study.

    Science.gov (United States)

    Ili, Pinar

    2016-07-01

    Exposure to UV radiation can cause histopathological and ultrastructural changes in the skin. Origanum hypericifolium, an endemic Turkish plant,essential oil is mainly composed of monoterpenes. The effects of undiluted O. hypericifolium oil on the ultrastructural characteristics of the UVB-irradiated dorsal skin of mice were investigated using transmission electron microscopy. The BALB/c mice were shaved of dorsal hair and randomly housed into 4 groups: 1: control; 2: UVB-irradiated; 3: oil applied; and 4: oil applied and UVB-irradiated. The oil was applied topically to the dorsal skins of the mice on alternate days for 1week prior to UVB exposure. The skins were irradiated for a total dose of 3.5J/cm(2). The sections were stained with hematoxylin and eosin, semithin sections were stained with toluidine blue and ultrathin sections were contrasted with uranyl acetate/lead citrate. There were histopathological changes such as parakeratosis and squamous hyperplasia in the epidermal cell layers (Groups 3 and 4). There were also ultrastructural changes including lacunae formations throughout the stratum corneum layer (Groups 2, 3, and 4), enlargement of intercellular spaces (Groups 2 and 3), reduced desmosomes, narrow and elongated interdigitations, shortened, relatively indistinct and electron dense intermediate keratin filament bundles (Group 3). There were various sizes of cytoplasmic and perinucleolar vacuoles (Groups 3 and 4) and apoptotic bodies phagocytized by keratinocytes (Group 4). I conclude that undiluted oil has side-effects and the potential to inflict injury to the skin. The oil does not ameliorate the negative effects of UVB on epidermal skin cells.

  18. Docosahexaenoic acid inhibits UVB-induced activation of NF-κB and expression of COX-2 and NOX-4 in HR-1 hairless mouse skin by blocking MSK1 signaling.

    Directory of Open Access Journals (Sweden)

    Mostafizur Rahman

    Full Text Available Exposure to ultraviolet-B (UVB radiation induces inflammation and photocarcinogenesis in mammalian skin. Docosahexaenoic acid (DHA, a representative ω-3 polyunsaturated fatty acid, has been reported to possess anti-inflammatory and chemopreventive properties. In the present study, we investigated the molecular mechanisms underlying the inhibitory effects of DHA on UVB-induced inflammation in mouse skin. Our study revealed that topical application of DHA prior to UVB irradiation attenuated the expression of cyclooxygenase-2 (COX-2 and NAD(PH:oxidase-4 (NOX-4 in hairless mouse skin. DHA pretreatment also attenuated UVB-induced DNA binding of nuclear factor-kappaB (NF-κB through the inhibition of phosphorylation of IκB kinase-α/β, phosphorylation and degradation of IκBα and nuclear translocation of p50 and p65. In addition, UVB-induced phosphorylation of p65 at the serine 276 residue was significantly inhibited by topical application of DHA. Irradiation with UVB induced phosphorylation of mitogen and stress-activated kinase-1 (MSK1, extracellular signal-regulated kinase (ERK and p38 mitogen-activated protein (MAP kinase, and all these events were attenuated by pretreatment with DHA. Blocking ERK and p38 MAP kinase signaling by U0126 and SB203580, respectively, diminished MSK1 phosphorylation in UVB-irradiated mouse skin. Pretreatment with H-89, a pharmacological inhibitor of MSK1, abrogated UVB-induced activation of NF-κB and the expression of COX-2 and NOX-4 in mouse skin. In conclusion, topically applied DHA inhibits the UVB-induced activation of NF-κB and the expression of COX-2 and NOX-4 by blocking the phosphorylation of MSK1, a kinase downstream of ERK and p38 MAP kinase, in hairless mouse skin.

  19. Roughness threshold for cell attachment and proliferation on plasma micro-nanotextured polymeric surfaces: the case of primary human skin fibroblasts and mouse immortalized 3T3 fibroblasts

    Science.gov (United States)

    Bourkoula, A.; Constantoudis, V.; Kontziampasis, D.; Petrou, P. S.; Kakabakos, S. E.; Tserepi, A.; Gogolides, E.

    2016-08-01

    Poly(methyl methacrylate) surfaces have been micro-nanotextured in oxygen plasmas with increasing ion energy, leading to micro-nanotopography characterized by increased root mean square roughness, correlation length and fractal dimension. Primary human skin fibroblasts and mouse immortalized 3T3 fibroblasts were cultured on these surfaces and the number of adhering cells, their proliferation rate and morphology (cytoplasm and nucleus area) were evaluated as a function of roughness height, correlation length, and fractal dimension. A roughness threshold behavior was observed for both types of cells leading to dramatic cell number decrease above this threshold, which is almost similar for the two types of cells, despite their differences in size and stiffness. The results are discussed based on two theoretical models, which are reconciled and unified when the elastic moduli and the size of the cells are taken into account.

  20. MicroRNA-21a-5p Functions on the Regulation of Melanogenesis by Targeting Sox5 in Mouse Skin Melanocytes.

    Science.gov (United States)

    Wang, Pengchao; Zhao, Yuanyuan; Fan, Ruiwen; Chen, Tianzhi; Dong, Changsheng

    2016-06-24

    MicroRNAs (miRNAs) play an important role in regulating almost all biological processes. miRNAs bind to the 3' untranslated region (UTR) of mRNAs by sequence matching. In a previous study, we demonstrated that miR-21 was differently expressed in alpaca skin with different hair color. However, the molecular and cellular mechanisms for miR-21 to regulate the coat color are not yet completely understood. In this study, we transfected miR-21a-5p into mouse melanocytes and demonstrated its function on melanogenesis of miR-21a-5p by targeting Sox5, which inhibits melanogenesis in mouse melanocytes. The results suggested that miR-21a-5p targeted Sox5 gene based on the binding site in 3' UTR of Sox5 and overexpression of miR-21a-5p significantly down-regulated Sox5 mRNA and protein expression. Meanwhile, mRNA and protein expression of microphthalmia transcription factor (MITF) and Tyrosinase (TYR) were up-regulated, which subsequently make the melanin production in melanocytes increased. The results suggest that miR-21a-5p regulates melanogenesis via MITF by targeting Sox5.

  1. Retinoic acid promotes the proliferation of primordial germ cell-like cells differentiated from mouse skin-derived stem cells in vitro.

    Science.gov (United States)

    Tan, Hui; Wang, Jun-Jie; Cheng, Shun-Feng; Ge, Wei; Sun, Yuan-Chao; Sun, Xiao-Feng; Sun, Rui; Li, Lan; Li, Bo; Shen, Wei

    2016-02-01

    Skin-derived stem cells (SDSCs) have the potential to differentiate into gametes and are a potential resource for research and clinical applications. Sufficient amount of primordial germ cells (PGCs) is an important requirement for successful differentiation of SDSCs into gametes in vitro. Retinoic acid (RA), a vitamin A-derived small lipophilic molecule, promotes the growth of PGCs in vivo; however, the role of RA on the proliferation of PGC-like cells (PGCLCs) derived from SDSCs remains unknown. In this study, SDSCs were induced to differentiate into the embryoid body and cocultured with mouse fibroblasts to form PGCLCs. The proliferation of PGCLCs with the presence of various concentrations of RA was investigated in vitro. Immunofluorescence labeling showed that the 5-Bromo-2-deoxyUridine-positive ratio of PGCLCs was increased after the cells were treated with 5-μM RA, and flow cytometry results showed that the number of cells in the S phase was increased significantly. The messenger RNA expression levels of cell cycle-related genes, CCND1 and CDK2, were also increased. Furthermore, RA effectively promoted the external proliferation of endogenous PGCs when 11.5-days postcoitum fetal mouse genital ridges were cultured in vitro. In conclusion, 5-μM RA promoted the proliferation of SDSCs-derived PGCLCs and endogenous PGCs. Our study will provide a valuable model system for studying the differentiation of stem cells into gametes in vitro.

  2. In-vivo and label-free imaging of cellular and tissue structures in mouse ear skin by using second- and third-harmonic generation microscopy

    Science.gov (United States)

    Lee, Eung Jang; Kim, Boram; Ahn, Hong-Gyu; Park, Seung-Han; Cheong, Eunji; Lee, Sangyoup

    2015-02-01

    A video-rate multimodal microscope, which can obtain second- and third- harmonic generation (SHG and THG) images simultaneously, is developed for investigating cellular and tissue structures in mouse ear skin. By utilizing in-vivo video-rate epi-detected SHG and THG microscopy, we successfully demonstrate that combined images of subcutaneous cellular components and peripheral nerve fibers, together with the collagen fiber, in the mouse ear pinna can be obtained without employing fluorescent probes. We also show that the flow of red blood cells and the diameter change of arteriole-like blood vessels can be visualized with femtosecond laser pulses with a wavelength of 1036 nm. In particular, the epi-THG contrast images of the blood-vessel walls display clearly the difference between the arteriole-like and the venule capillary-like blood-vessel types. We should emphasize that our newly-developed microscope system has a unique feature in that it can produce simultaneous in-vivo label-free SHG and THG images in contrast to the conventional confocal and two-photon microscopes.

  3. MicroRNA-21a-5p Functions on the Regulation of Melanogenesis by Targeting Sox5 in Mouse Skin Melanocytes

    Directory of Open Access Journals (Sweden)

    Pengchao Wang

    2016-06-01

    Full Text Available MicroRNAs (miRNAs play an important role in regulating almost all biological processes. miRNAs bind to the 3′ untranslated region (UTR of mRNAs by sequence matching. In a previous study, we demonstrated that miR-21 was differently expressed in alpaca skin with different hair color. However, the molecular and cellular mechanisms for miR-21 to regulate the coat color are not yet completely understood. In this study, we transfected miR-21a-5p into mouse melanocytes and demonstrated its function on melanogenesis of miR-21a-5p by targeting Sox5, which inhibits melanogenesis in mouse melanocytes. The results suggested that miR-21a-5p targeted Sox5 gene based on the binding site in 3′ UTR of Sox5 and overexpression of miR-21a-5p significantly down-regulated Sox5 mRNA and protein expression. Meanwhile, mRNA and protein expression of microphthalmia transcription factor (MITF and Tyrosinase (TYR were up-regulated, which subsequently make the melanin production in melanocytes increased. The results suggest that miR-21a-5p regulates melanogenesis via MITF by targeting Sox5.

  4. Autofluorescence imaging device for real-time detection and tracking of pathogenic bacteria in a mouse skin wound model: preclinical feasibility studies

    Science.gov (United States)

    Wu, Yichao Charlie; Kulbatski, Iris; Medeiros, Philip J.; Maeda, Azusa; Bu, Jiachuan; Xu, Lizhen; Chen, Yonghong; DaCosta, Ralph S.

    2014-08-01

    Bacterial infection significantly impedes wound healing. Clinical diagnosis of wound infections is subjective and suboptimal, in part because bacteria are invisible to the naked eye during clinical examination. Moreover, bacterial infection can be present in asymptomatic patients, leading to missed opportunities for diagnosis and treatment. We developed a prototype handheld autofluorescence (AF) imaging device (Portable Real-time Optical Detection, Identification and Guidance for Intervention-PRODIGI) to noninvasively visualize and measure bacterial load in wounds in real time. We conducted preclinical pilot studies in an established nude mouse skin wound model inoculated with bioluminescent Staphylococcus aureus bacteria. We tested the feasibility of longitudinal AF imaging for in vivo visualization of bacterial load in skin wounds, validated by bioluminescence imaging. We showed that bacteria (S. aureus), occult to standard examination, can be visualized in wounds using PRODIGI. We also detected quantitative changes in wound bacterial load over time based on the antibiotic treatment and the correlation of bacterial AF intensity with bacterial load. AF imaging of wounds offers a safe, noninvasive method for visualizing the presence, location, and extent of bacteria as well as measuring relative changes in bacterial load in wounds in real time.

  5. An EPR method for estimating activity of antioxidants in mouse skin using an anthralin-derived radical model.

    Science.gov (United States)

    Kawai, Sayo; Matsumoto, Ken-Ichiro; Utsumi, Hideo

    2010-03-01

    Inhibitory effects of intravenously or orally administered antioxidants on the anthralin-derived radical generated in skin (mainly in the epidermis) of living mice by ultraviolet-A (UVA) irradiation were estimated. Anthralin was applied to the dorsal skin of living mice and the mice were then exposed to UVA. The EPR signal intensity in skin tissue strips obtained from mice after anthralin-UVA treatment was measured by an X-band EPR spectrometer. Several common antioxidants such as ascorbate, glutathione and Trolox (a vitamin E analogue) intravenously administered to mice reduced anthralin-derived radical generation. Trolox showed the most prolonged and powerful effect. Intravenous injection of a clinically used cerebral neuroprotective drug, Edarabone (Radicut), also showed depletion for the anthralin-derived radical. Oral administration of a commercialized nutritional supplement (a cocktail of 17 herbals and vitamins) also attenuated the anthralin-derived radical. The anthralin-UVA treatment model for antioxidant activity in the epidermis is a potentially feasible method to estimate activity of antioxidants in the body.

  6. Selective inhibition of JNK with a peptide inhibitor attenuates pain hypersensitivity and tumor growth in a mouse skin cancer pain model.

    Science.gov (United States)

    Gao, Yong-Jing; Cheng, Jen-Kun; Zeng, Qing; Xu, Zhen-Zhong; Decosterd, Isabelle; Xu, Xiaoyin; Ji, Ru-Rong

    2009-09-01

    Cancer pain significantly affects the quality of cancer patients, and current treatments for this pain are limited. C-Jun N-terminal kinase (JNK) has been implicated in tumor growth and neuropathic pain sensitization. We investigated the role of JNK in cancer pain and tumor growth in a skin cancer pain model. Injection of luciferase-transfected B16-Fluc melanoma cells into a hindpaw of mouse induced robust tumor growth, as indicated by increase in paw volume and fluorescence intensity. Pain hypersensitivity in this model developed rapidly (Tumor growth was associated with JNK activation in tumor mass, dorsal root ganglion (DRG), and spinal cord and a peripheral neuropathy, such as loss of nerve fibers in the hindpaw skin and induction of ATF-3 expression in DRG neurons. Repeated systemic injections of D-JNKI-1 (6 mg/kg, i.p.), a selective and cell-permeable peptide inhibitor of JNK, produced an accumulative inhibition of mechanical allodynia and heat hyperalgesia. A bolus spinal injection of D-JNKI-1 also inhibited mechanical allodynia. Further, JNK inhibition suppressed tumor growth in vivo and melanoma cell proliferation in vitro. In contrast, repeated injections of morphine (5 mg/kg), a commonly used analgesic for terminal cancer, produced analgesic tolerance after 1 day and did not inhibit tumor growth. Our data reveal a marked peripheral neuropathy in this skin cancer model and important roles of the JNK pathway in cancer pain development and tumor growth. JNK inhibitors such as D-JNKI-1 may be used to treat cancer pain.

  7. Mutation spectrum in sunlight-exposed mouse skin epidermis: small but appreciable contribution of oxidative stress-mediated mutagenesis

    Energy Technology Data Exchange (ETDEWEB)

    Ikehata, Hironobu [Department of Cell Biology, Graduate School of Medicine, Tohoku University, Sendai 980-8575 (Japan)]. E-mail: ikehata@mail.tains.tohoku.ac.jp; Nakamura, Shingo [Department of Cell Biology, Graduate School of Medicine, Tohoku University, Sendai 980-8575 (Japan); Department of Radiobiology, Institute for Environmental Sciences, Aomori 039-3212 (Japan); Asamura, Takaaki [Department of Cell Biology, Graduate School of Medicine, Tohoku University, Sendai 980-8575 (Japan); Ono, Tetsuya [Department of Cell Biology, Graduate School of Medicine, Tohoku University, Sendai 980-8575 (Japan)

    2004-11-22

    We studied the mutations induced in skin by sunlight using transgenic Muta{sup TM} mice. Noon sunlight during summer at Sendai, Japan induced mutations efficiently in both epidermis and dermis. The mutant frequency (MF) in epidermis reached nearly 0.5% during the first 40 min irradiation but became saturated at this level with the appearance of skin inflammation after further irradiation. At the equivalent inflammatory dose, sunlight was twice as genotoxic as 313 nm-peak UVB. The 81 mutations detected in 80 lacZ transgene mutants isolated from the sunlight-exposed epidermis were dominated by C {yields} T transitions (89%), occurring exclusively at dipyrimidine sites, and also included a CC {yields} TT tandem substitution. Thus, the sunlight-induced mutation spectrum is highly UV-specific, quite similar to that induced by UVB but significantly different from that induced by UVA. Although oxidative damage-related C {yields} A transversions were detected only in five mutants (6%), their frequency was elevated to at least 15 times the background level, suggesting that the contribution of UVA-mediated oxidative stress is comparatively small but considerable. An analysis of bases adjacent to the mutated cytosines revealed that the sunlight-induced mutations prefer 5'-TC-3' dipyrimidine sites to 5'-CC-3' and 5'-CT-3'. The distribution of the frequent C {yields} T transition sites in the transgene was well associated with the CpG motif, which is known to be completely methylated in the gene, and quite similar to that induced by UVB rather than that by UVA. Thus, the UVB component contributes to the sunlight-induced mutations in the mammalian skin much more than the UVA component, whose influence through reactive oxygen species (ROS)-mediated mutagenesis is still appreciable.

  8. Apoptosis is an early event during phthalocyanine photodynamic therapy-induced ablation of chemically induced squamous papillomas in mouse skin.

    Science.gov (United States)

    Agarwal, R; Korman, N J; Mohan, R R; Feyes, D K; Jawed, S; Zaim, M T; Mukhtar, H

    1996-04-01

    Photodynamic therapy (PDT) is a promising new modality to treat malignant neoplasms including superficial skin cancers. In our search for an ideal photosensitizer for PDT, Pc 4, a silicon phthalocyanine, has shown promising results both in in vitro assays and in implanted tumors. In this study we assessed the efficacy of Pc 4 PDT in the ablation of murine skin tumors; and the evidence for apoptosis during tumor ablation was also obtained. The Pc 4 was administered through tail vein injection to SENCAR mice bearing chemically induced squamous papillomas, and 24 h later the lesions were illuminated with an argon ion-pumped dye laser tuned at 675 nm for a total light dose of 135 J/cm2. Within 72-96 h, almost complete tumor shrinkage occurred; no tumor regrowth was observed up to 90 days post-PDT. As evident by nucleosome-size DNA fragmentation, appearance of apoptotic bodies in hematoxylin and eosin staining and direct immunoperoxidase detection of digoxigenin-labeled genomic DNA in sections, apoptosis was clearly evident 6 h post-PDT at which time tumor shrinkage was less than 30%. The apoptotic bodies, as evident by the condensation of chromatin material around the periphery of the nucleus and increased vacuolization of the cytoplasm, were also observed in electron microscopic studies of the tumor tissues following Pc 4 PDT. The extent of apoptosis was greater at 15 h than at 6 and 10 h post-PDT. Taken together, our results clearly show that Pc 4 may be an effective photosensitizer for PDT of nonmelanoma skin cancer, and that apoptosis is an early event during this process.

  9. Fluorescent peptide biosensor for monitoring CDK4/cyclin D kinase activity in melanoma cell extracts, mouse xenografts and skin biopsies.

    Science.gov (United States)

    Prével, Camille; Pellerano, Morgan; González-Vera, Juan A; Henri, Pauline; Meunier, Laurent; Vollaire, Julien; Josserand, Véronique; Morris, May C

    2016-11-15

    Melanoma constitutes the most aggressive form of skin cancer, which further metastasizes into a deadly form of cancer. The p16(INK4a)-Cyclin D-CDK4/6-pRb pathway is dysregulated in 90% of melanomas. CDK4/Cyclin D kinase hyperactivation, associated with mutation of CDK4, amplification of Cyclin D or loss of p16(INK4a) leads to increased risk of developing melanoma. This kinase therefore constitutes a key biomarker in melanoma and an emerging pharmacological target, however there are no tools enabling direct detection or quantification of its activity. Here we report on the design and application of a fluorescent peptide biosensor to quantify CDK4 activity in melanoma cell extracts, skin biopsies and melanoma xenografts. This biosensor provides sensitive means of comparing CDK4 activity between different melanoma cell lines and further responds to CDK4 downregulation by siRNA or small-molecule inhibitors. By affording means of monitoring CDK4 hyperactivity consequent to cancer-associated molecular alterations in upstream signaling pathways that converge upon this kinase, this biosensor offers an alternative to immunological identification of melanoma-specific biomarkers, thereby constituting an attractive tool for diagnostic purposes, providing complementary functional information to histological analysis, of particular utility for detection of melanoma onset in precancerous lesions. This is indeed the first fluorescent peptide biosensor which has been successfully implemented to monitor kinase activity in skin samples and melanoma tumour xenografts. Moreover by enabling to monitor response to CDK4 inhibitors, this biosensor constitutes an attractive companion assay to identify compounds of therapeutic relevance for melanoma.

  10. 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.

    Science.gov (United States)

    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.

  11. The excimer lamp induces cutaneous nerve degeneration and reduces scratching in a dry-skin mouse model.

    Science.gov (United States)

    Kamo, Atsuko; Tominaga, Mitsutoshi; Kamata, Yayoi; Kaneda, Kazuyuki; Ko, Kyi C; Matsuda, Hironori; Kimura, Utako; Ogawa, Hideoki; Takamori, Kenji

    2014-12-01

    Epidermal hyperinnervation, which is thought to underlie intractable pruritus, has been observed in patients with atopic dermatitis (AD). The epidermal expression of axonal guidance molecules has been reported to regulate epidermal hyperinnervation. Previously, we showed that the excimer lamp has antihyperinnervative effects in nonpruritic dry-skin model mice, although epidermal expression of axonal guidance molecules was unchanged. Therefore, we investigated the antipruritic effects of excimer lamp irradiation and its mechanism of action. A single irradiation of AD model mice significantly inhibited itch-related behavior 1 day later, following improvement in the dermatitis score. In addition, irradiation of nerve fibers formed by cultured dorsal root ganglion neurons increased bleb formation and decreased nerve fiber expression of nicotinamide mononucleotide adenylyl transferase 2, suggesting degenerative changes in these fibers. We also analyzed whether attaching a cutoff excimer filter (COF) to the lamp, thus decreasing cytotoxic wavelengths, altered hyperinnervation and the production of cyclobutane pyrimidine dimer (CPD), a DNA damage marker, in dry-skin model mice. Irradiation with COF decreased CPD production in keratinocytes, as well as having an antihyperinnervative effect, indicating that the antipruritic effects of excimer lamp irradiation with COF are due to induction of epidermal nerve degeneration and reduced DNA damage.

  12. Identification of an mtDNA mutation hot spot in UV-induced mouse skin tumors producing altered cellular biochemistry.

    Science.gov (United States)

    Jandova, Jana; Eshaghian, Alex; Shi, Mingjian; Li, Meiling; King, Lloyd E; Janda, Jaroslav; Sligh, James E

    2012-02-01

    There is increasing awareness of the role of mtDNA alterations in the development of cancer, as mtDNA point mutations are found at high frequency in a variety of human tumors. To determine the biological effects of mtDNA mutations in UV-induced skin tumors, hairless mice were irradiated to produce tumors, and the tumor mtDNAs were screened for single-nucleotide changes using temperature gradient capillary electrophoresis (TGCE), followed by direct sequencing. A mutation hot spot (9821insA) in the mitochondrially encoded tRNA arginine (mt-Tr) locus (tRNA(Arg)) was discovered in approximately one-third of premalignant and malignant skin tumors. To determine the functional relevance of this particular mutation in vitro, cybrid cell lines containing different mt-Tr (tRNA(Arg)) alleles were generated. The resulting cybrid cell lines contained the same nuclear genotype and differed only in their mtDNAs. The biochemical analysis of the cybrids revealed that the mutant haplotype is associated with diminished levels of complex I protein (CI), resulting in lower levels of baseline oxygen consumption and lower cellular adenosine triphosphate (ATP) production. We hypothesize that this specific mtDNA mutation alters cellular biochemistry, supporting the development of keratinocyte neoplasia.

  13. Potent immunity to low doses of influenza vaccine by probabilistic guided micro-targeted skin delivery in a mouse model.

    Directory of Open Access Journals (Sweden)

    Germain J P Fernando

    Full Text Available BACKGROUND: Over 14 million people die each year from infectious diseases despite extensive vaccine use [1]. The needle and syringe--first invented in 1853--is still the primary delivery device, injecting liquid vaccine into muscle. Vaccines could be far more effective if they were precisely delivered into the narrow layer just beneath the skin surface that contains a much higher density of potent antigen-presenting cells (APCs essential to generate a protective immune response. We hypothesized that successful vaccination could be achieved this way with far lower antigen doses than required by the needle and syringe. METHODOLOGY/PRINCIPAL FINDINGS: To meet this objective, using a probability-based theoretical analysis for targeting skin APCs, we designed the Nanopatch, which contains an array of densely packed projections (21025/cm(2 invisible to the human eye (110 microm in length, tapering to tips with a sharpness of <1000 nm, that are dry-coated with vaccine and applied to the skin for two minutes. Here we show that the Nanopatches deliver a seasonal influenza vaccine (Fluvax 2008 to directly contact thousands of APCs, in excellent agreement with theoretical prediction. By physically targeting vaccine directly to these cells we induced protective levels of functional antibody responses in mice and also protection against an influenza virus challenge that are comparable to the vaccine delivered intramuscularly with the needle and syringe--but with less than 1/100(th of the delivered antigen. CONCLUSIONS/SIGNIFICANCE: Our results represent a marked improvement--an order of magnitude greater than reported by others--for injected doses administered by other delivery methods, without reliance on an added adjuvant, and with only a single vaccination. This study provides a proven mathematical/engineering delivery device template for extension into human studies--and we speculate that successful translation of these findings into humans could

  14. The heparan sulphate deficient Hspg2 exon 3 null mouse displays reduced deposition of TGF-β1 in skin compared to C57BL/6 wild type mice.

    Science.gov (United States)

    Shu, Cindy; Smith, Susan M; Melrose, James

    2016-06-01

    This was an observational study where we examined the role of perlecan HS on the deposition of TGF-β1 in C57BL/6 and Hspg2(∆3-/∆3-) perlecan exon 3 null mouse skin. Despite its obvious importance in skin repair and tissue homeostasis no definitive studies have immunolocalised TGF-β1 in skin in WT or Hspg2(∆3-/∆3-) perlecan exon 3 null mice. Vertical parasagittal murine dorsal skin from 3, 6 and 12 week old C57BL/6 and Hspg2(∆3-/∆3-) mice were fixed in neutral buffered formalin, paraffin embedded and 4 μm sections stained with Mayers haematoxylin and eosin (H & E). TGF-β1 was immunolocalised using a rabbit polyclonal antibody, heat retrieval and the Envision NovaRED detection system. Immunolocalisation of TGF-β1 differed markedly in C57BL/6 and Hspg2(∆3-/∆3-) mouse skin, ablation of exon 3 of Hspg2 resulted in a very severe reduction in the deposition of TGF-β1 in skin 3-12 weeks postnatally. The reduced deposition of TGF-β1 observed in the present study would be expected to impact detrimentally on the remodelling and healing capacity of skin in mutant mice compounding on the poor wound-healing properties already reported for perlecan exon 3 null mice due to an inability to signal with FGF-2 and promote angiogenic repair processes. TGF-β1 also has cell mediated effects in tissue homeostasis and matrix stabilisation a reduction in TGF-β1 deposition would therefore be expected to detrimentally impact on skin homeostasis in the perlecan mutant mice.

  15. Phototumorigenesis studies of 5-methoxypsoralen in bergamot oil: evaluation and modification of risk of human use in an albino mouse skin model.

    Science.gov (United States)

    Young, A R; Walker, S L; Kinley, J S; Plastow, S R; Averbeck, D; Morlière, P; Dubertret, L

    1990-11-01

    The skin of the female hairless albino mouse (Skh 1) was used to study the enhancement of solar simulated radiation (SSR) tumorigenesis by 5-methoxypsoralen (5-MOP) in model perfumes that contain bergamot oil. This work was done in association with yeast mutagenicity studies and human skin phototoxicity studies. Analyses of time-to-onset of tumour observation with 5-MOP at 0, 5, 15 and 50 ppm show a highly significant 5-MOP dose effect and the data indicate that 5-MOP has phototumorigenic potential even at 5 ppm. The addition of 0.5% UVB and 0.5% UVA sunscreens significantly reduces the tumorigenicity associated with the vehicle (i.e. 5-MOP at 0 ppm) and 5-MOP at all concentrations. Pairwise comparisons of 5-MOP (at 5 or 15 ppm) plus sunscreens with vehicle plus sunscreens show that the sunscreens afford total protection at the lower 5-MOP concentrations. Additional studies show that a 5-6 h delay between 5-MOP application and SSR exposure defers the time-to-onset of tumours as does intermittent 5-MOP and SSR treatment. A comparison of 5-MOP at 50 ppm in bergamot oil with 5-MOP at 50 ppm prepared from pure 5-MOP crystals shows identical results, indicating that the active phototumorigenic agent in bergamot oil is 5-MOP and not other related compounds, which may be present at greater concentrations. Analyses of tumour histology at death show, in general, similar patterns of malignancy for all groups. Thus although it is possible to delay tumorigenesis by various strategies, the tumours that eventually develop are just as likely to be malignant, if not more so, when compared with non-delayed groups.

  16. Vitamin D for combination photodynamic therapy of skin cancer in individuals with vitamin D deficiency: Insights from a preclinical study in a mouse model of squamous cell carcinoma

    Science.gov (United States)

    Anand, Sanjay; Thomas, Erik; Hasan, Tayyaba; Maytin, Edward V.

    2016-03-01

    Combination photodynamic therapy (cPDT) in which vitamin D (VD) is given prior to aminolevulinate, a precursor (pro-drug) for protoporphyrin IX (PpIX), is an approach developed in our laboratory. We previously showed that 1α,25- dihydroxyvitamin D3 (calcitriol), given prior to PDT, enhances accumulation of PpIX and improves cell death post-PDT in a mouse skin cancer model. However, since calcitriol poses a risk for hypercalcemia, we replaced systemic calcitriol with oral cholecalciferol (D3), administered as a high (tenfold, "10K") diet over a ten-day period. Here, we ask whether VD deficiency might alter the response to cPDT. Nude mice were fed a VD-deficient diet for at least 4 weeks ("deficient"); controls were fed a normal 1,000 IU/kg diet ("1K"). Human A431 cells were implanted subcutaneously and mice were switched to the 10K diet or continued on their baseline diets (controls). In other experiments, mice received a human equivalent dose of 50,000 IU D3 by oral gavage, to simulate administration of a single, high-dose VD pill. At various times, tumors were harvested and serum was collected to measure levels of VD metabolic intermediates. A significant increase in PpIX levels and in the expression of differentiation and proliferation markers in tumor tissue was observed after VD supplementation of both the deficient and 1K mice. Further results describing mechanistic details of PpIX enhancement through alteration of heme- and VD-metabolic enzyme levels will be presented. Based on these results, a clinical study using oral vitamin D prior to PDT for human skin cancer should be performed.

  17. Polycyclic aromatic hydrocarbons as skin carcinogens: comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse.

    Science.gov (United States)

    Siddens, Lisbeth K; Larkin, Andrew; Krueger, Sharon K; Bradfield, Christopher A; Waters, Katrina M; Tilton, Susan C; Pereira, Cliff B; Löhr, Christiane V; Arlt, Volker M; Phillips, David H; Williams, David E; Baird, William M

    2012-11-01

    The polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BaP), was compared to dibenzo[def,p]chrysene (DBC) and combinations of three environmental PAH mixtures (coal tar, diesel particulate and cigarette smoke condensate) using a two stage, FVB/N mouse skin tumor model. DBC (4nmol) was most potent, reaching 100% tumor incidence with a shorter latency to tumor formation, less than 20 weeks of 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion compared to all other treatments. Multiplicity was 4 times greater than BaP (400 nmol). Both PAHs produced primarily papillomas followed by squamous cell carcinoma and carcinoma in situ. Diesel particulate extract (1 mg SRM 1650b; mix 1) did not differ from toluene controls and failed to elicit a carcinogenic response. Addition of coal tar extract (1 mg SRM 1597a; mix 2) produced a response similar to BaP. Further addition of 2 mg of cigarette smoke condensate (mix 3) did not alter the response with mix 2. PAH-DNA adducts measured in epidermis 12 h post initiation and analyzed by ³²P post-labeling, did not correlate with tumor incidence. PAH-dependent alteration in transcriptome of skin 12 h post initiation was assessed by microarray. Principal component analysis (sum of all treatments) of the 922 significantly altered genes (p<0.05), showed DBC and BaP to cluster distinct from PAH mixtures and each other. BaP and mixtures up-regulated phase 1 and phase 2 metabolizing enzymes while DBC did not. The carcinogenicity with DBC and two of the mixtures was much greater than would be predicted based on published Relative Potency Factors (RPFs).

  18. Penetration enhancement in mouse skin and lipolysis in adipocytes by TAT-GKH, a new cosmetic ingredient.

    Science.gov (United States)

    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.

  19. Transport behavior of hairless mouse skin during constant current DC iontophoresis, part 2: iontophoresis of nonionic molecules with cotransport of polystyrene sulfonate oligomers.

    Science.gov (United States)

    Liddell, Mark R; Li, S Kevin; Higuchi, William I

    2011-07-01

    The purpose of this study was to characterize changes that occur in the iontophoretic transport of nonionic probe permeants in hairless mouse skin epidermal membrane from the anode to cathode when polystyrene sulfonate (PSS) oligomers are cotransported from the cathode to anode. The experiments were conducted with trace levels of the nonionic probe permeants: urea, mannitol, and raffinose. In order to systematically assess changes that occur as a result of having PSS in the cathodal chamber, the steady-state transport parameters of the membrane and the experimental permeability coefficients of the probe permeants were determined and compared with results obtained from earlier baseline experiments where both the cathodal and anodal chamber media were phosphate buffered saline. In addition, the physicochemical properties of the PSS solutions were determined including the solution viscosity and conductance as well as the mobilities of individual PSS oligomers. The effective pore radii of the transport pathways were calculated using a theoretical expression based on simultaneous diffusion and electroosmosis. Compared with the baseline results, the calculated radii were found to have increased up to around twofold and the iontophoretic fluxes of the probe permeants increased by as much sixfold.

  20. Dietary lipid varying in corn and coconut oil influences protein kinase C in phorbol ester-treated mouse skin.

    Science.gov (United States)

    Mouat, M F; Locniskar, M F

    1998-01-01

    An earlier study indicated that increased levels of corn oil in the diet resulted in decreased tumor yield after promotion by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate in Sencar mouse epidermis (J Leyton, ML Lee, M Locniskar, MA Belury, TJ Slaga, et al. Cancer Res 51, 907-915, 1991). In the present study we investigated whether corn oil diets could alter the subcellular distribution and activity of protein kinase C (PKC), which is part of an important signaling pathway in carcinogenesis. We used three 15% (wt/wt) fat semipurified diets containing three ratios of corn oil to coconut oil: 1.0%:14.0% (Diet L), 7.9%:7.1% (Diet M), and 15.0%:0.0% (Diet H). The translocation to the membrane fraction of epidermal PKC by 12-O-tetradecanoylphorbol-13-acetate was decreased as the corn oil content of the diet was increased, and this correlates with the decrease in tumor yield. The translocation to the membrane fraction of specific isoforms of PKC was affected by increased dietary corn oil: the largest decreases were in cytosolic PKC-alpha and -beta, and the smallest change was in PKC-epsilon. The other isoforms, PKC-delta and -zeta, were unaffected. The major constituent of corn oil is linoleic acid, which did not affect the binding of phorbol ester to PKC, which suggests that inhibition of such binding was not responsible for the effects of increased dietary corn oil. Products of linoleic acid metabolism, i.e., arachidonic acid and 13-hydroxyoctadecadienoic acid, also did not affect the binding of phorbol ester to PKC. Thus the results of these studies suggest that the subcellular distributions of PKC and its isoforms can be modulated by dietary lipids.

  1. The selective PAC1 receptor agonist maxadilan inhibits neurogenic vasodilation and edema formation in the mouse skin.

    Science.gov (United States)

    Banki, E; Hajna, Zs; Kemeny, A; Botz, B; Nagy, P; Bolcskei, K; Toth, G; Reglodi, D; Helyes, Zs

    2014-10-01

    We have earlier shown that PACAP-38 decreases neurogenic inflammation. However, there were no data on its receptorial mechanism and the involvement of its PAC1 and VPAC1/2 receptors (PAC1R, VPAC1/2R) in this inhibitory effect. Neurogenic inflammation in the mouse ear was induced by topical application of the Transient Receptor Potential Ankyrin 1 (TRPA1) receptor activator mustard oil (MO). Consequent neurogenic edema, vasodilation and plasma leakage were assessed by measuring ear thickness with engineer's micrometer, detecting tissue perfusion by laser Doppler scanning and Evans blue or indocyanine green extravasation by intravital videomicroscopy or fluorescence imaging, respectively. Myeloperoxidase activity, an indicator of neutrophil infiltration, was measured from the ear homogenates with spectrophotometry. The selective PAC1R agonist maxadilan, the VPAC1/2R agonist vasoactive intestinal polypeptide (VIP) or the vehicle were administered i.p. 15 min before MO. Substance P (SP) concentration of the ear was assessed by radioimmunoassay. Maxadilan significantly diminished MO-induced neurogenic edema, increase of vascular permeability and vasodilation. These inhibitory effects of maxadilan may be partially due to the decreased substance P (SP) levels. In contrast, inhibitory effect of VIP on ear swelling was moderate, without any effect on MO-induced plasma leakage or SP release, however, activation of VPAC1/2R inhibited the increased microcirculation caused by the early arteriolar vasodilation. Neither the PAC1R, nor the VPAC1/2R agonist influenced the MO-evoked increase in tissue myeloperoxidase activity. These results clearly show that PAC1R activation inhibits acute neurogenic arterial vasodilation and plasma protein leakage from the venules, while VPAC1/2R stimulation is only involved in the attenuation of vasodilation.

  2. Carcinogenicity of the environmental pollutants cyclopenteno-(cd)pyrene and cyclopentano(cd)pyrene in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Cavalieri, E.; Rogan, E.; Toth, B.; Munhall, A.

    1981-01-01

    Cyclopenteno(cd)pyrene (CPEP) is a widespread environmental pollutant. This hydrocarbon and its 3,4-dihydro derivative, cyclopentano(cd)pyrene (CPAP), were tested on skin in a two-stage initiation-promotion experiment in CD-1 mice and by repeated application in Swiss mice. The biological effect of CPEP and CPAP was compared to that of benzo(a)-pyrene (BP). Nine-week-old female CD-1 mice in groups of 30 were treated every other day over a 20-day period at mini-dose levels of 0.18, 0.06 and 0.02 mumol of CPEP or CPAP in acetone. One group was treated with BP at the low mini-dose level. Initiation was followed by twice weekly application of tetradecanoyl phorbol acetate for 40 weeks. In the second experiments, nine-week-old female Swiss mice in groups of 30 were treated at dose levels of 1.8, 0.6 and 0.2 mumol CPEP or CPAP in acetone twice weekly for 30 weeks. One group was treated with BP at the low dose. CPAP was virtually inactive in both studies. In the initiation-promotion experiment CPEP was inactive at the low dose level, whereas BP exhibited significant tumorigenicity. At the medium and high doses CPEP showed weak, but statistically insignificant, tumorigenic activity. Repeated application of CPEP at the high, medium and low doses resulted in tumor incidences of 23, 37 and 57%, respectively. This reverse dose-response may be due to the relatively high cytotoxicity of CPEP, BP, which was compared to CPEP at the low dose, elicited tumors in 100% of the mice. Most of the CPEP-induced neoplasms were malignant and some metastasized to lungs and lymph nodes. The inactivity of CPAP suggests the carcinogenicity of CPEP is probably due to formation of the ultimate metabolite CPEP 3,4-oxide. In view of the abundance of CPEP in environmental and occupational pollutants, its moderately potent carcinogenicity may represent a potential health hazard.

  3. Photodynamic therapy using a novel irradiation source, LED lamp, is similarly effective to photodynamic therapy using diode laser or metal-halide lamp on DMBA- and TPA-induced mouse skin papillomas.

    Science.gov (United States)

    Takahashi, Hidetoshi; Nakajima, Susumu; Ogasawara, Koji; Asano, Ryuji; Nakae, Yoshinori; Sakata, Isao; Iizuka, Hajime

    2014-08-01

    Photodynamic therapy (PDT) is useful for superficial skin tumors such as actinic keratosis and Bowen disease. Although PDT is non-surgical and easily-performed treatment modality, irradiation apparatus is large and expensive. Using 7, 12-dimethylbenz[a]anthracene (DMBA) and 12-ο-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin papilloma model, we compared the efficacy of TONS501- and ALA-PDT with a LED lamp, a diode laser lamp or a metal-halide lamp on the skin tumor regression. TONS501-PDT using 660 nm LED lamp showed anti-tumor effect at 1 day following the irradiation and the maximal anti-tumor effect was observed at 3 days following the irradiation. There was no significant difference in the anti-tumor effects among TONS501-PDT using LED, TONS501-PDT using diode laser, and 5-aminolevulinic acid hydrochloride (ALA)-PDT using metal-halide lamp. Potent anti-tumor effect on DMBA- and TPA-induced mouse skin papilloma was observed by TONS501-PDT using 660 nm LED, which might be more useful for clinical applications.

  4. Polycyclic aromatic hydrocarbons as skin carcinogens: Comparison of benzo[a]pyrene, dibenzo[def,p]chrysene and three environmental mixtures in the FVB/N mouse

    Energy Technology Data Exchange (ETDEWEB)

    Siddens, Lisbeth K.; Larkin, Andrew [Department of Environmental and Molecular Toxicology, Oregon State University (United States); Superfund Research Center, Oregon State University (United States); Krueger, Sharon K. [Superfund Research Center, Oregon State University (United States); The Linus Pauling Institute, Oregon State University (United States); Bradfield, Christopher A. [McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53706 (United States); Waters, Katrina M.; Tilton, Susan C. [Superfund Research Center, Oregon State University (United States); Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Pereira, Cliff B. [Superfund Research Center, Oregon State University (United States); Deptartment of Statistics, Oregon State University, Corvallis, OR 97331 (United States); Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); Löhr, Christiane V. [Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331 (United States); Arlt, Volker M.; Phillips, David H. [Analytical and Environmental Sciences Division, MRC-HPA Centre for Environment and Health, King' s College London, London SE1 9NH (United Kingdom); Williams, David E., E-mail: david.williams@oregonstate.edu [Department of Environmental and Molecular Toxicology, Oregon State University (United States); Superfund Research Center, Oregon State University (United States); The Linus Pauling Institute, Oregon State University (United States); Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); and others

    2012-11-01

    The polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BaP), was compared to dibenzo[def,p]chrysene (DBC) and combinations of three environmental PAH mixtures (coal tar, diesel particulate and cigarette smoke condensate) using a two stage, FVB/N mouse skin tumor model. DBC (4 nmol) was most potent, reaching 100% tumor incidence with a shorter latency to tumor formation, less than 20 weeks of 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion compared to all other treatments. Multiplicity was 4 times greater than BaP (400 nmol). Both PAHs produced primarily papillomas followed by squamous cell carcinoma and carcinoma in situ. Diesel particulate extract (1 mg SRM 1650b; mix 1) did not differ from toluene controls and failed to elicit a carcinogenic response. Addition of coal tar extract (1 mg SRM 1597a; mix 2) produced a response similar to BaP. Further addition of 2 mg of cigarette smoke condensate (mix 3) did not alter the response with mix 2. PAH-DNA adducts measured in epidermis 12 h post initiation and analyzed by {sup 32}P post‐labeling, did not correlate with tumor incidence. PAH‐dependent alteration in transcriptome of skin 12 h post initiation was assessed by microarray. Principal component analysis (sum of all treatments) of the 922 significantly altered genes (p < 0.05), showed DBC and BaP to cluster distinct from PAH mixtures and each other. BaP and mixtures up-regulated phase 1 and phase 2 metabolizing enzymes while DBC did not. The carcinogenicity with DBC and two of the mixtures was much greater than would be predicted based on published Relative Potency Factors (RPFs). -- Highlights: ► Dibenzo[def,p]chrysene (DBC), 3 PAH mixtures, benzo[a]pyrene (BaP) were compared. ► DBC and 2 PAH mixtures were more potent than Relative Potency Factor estimates. ► Transcriptome profiles 12 hours post initiation were analyzed by microarray. ► Principle components analysis of alterations revealed treatment-based clustering. ► DBC gave a unique

  5. Cytochrome P450 1b1 in polycyclic aromatic hydrocarbon (PAH)-induced skin carcinogenesis: Tumorigenicity of individual PAHs and coal-tar extract, DNA adduction and expression of select genes in the Cyp1b1 knockout mouse

    Energy Technology Data Exchange (ETDEWEB)

    Siddens, Lisbeth K. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States); Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Bunde, Kristi L. [College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331 (United States); Harper, Tod A. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 (United States); Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); McQuistan, Tammie J. [Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 (United States); Löhr, Christiane V. [Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331 (United States); Bramer, Lisa M. [Applied Statistics and Computational Modeling, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Waters, Katrina M. [Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Tilton, Susan C. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States); Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Krueger, Sharon K. [Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331 (United States); Superfund Research Center, Oregon State University, Corvallis, OR 97331 (United States); Linus Pauling Institute, Oregon State University, Corvallis, OR 97331 (United States); and others

    2015-09-01

    FVB/N mice wild-type, heterozygous or null for Cyp 1b1 were used in a two-stage skin tumor study comparing PAH, benzo[a]pyrene (BaP), dibenzo[def,p]chrysene (DBC), and coal tar extract (CTE, SRM 1597a). Following 20 weeks of promotion with TPA the Cyp 1b1 null mice, initiated with DBC, exhibited reductions in incidence, multiplicity, and progression. None of these effects were observed with BaP or CTE. The mechanism of Cyp 1b1-dependent alteration of DBC skin carcinogenesis was further investigated by determining expression of select genes in skin from DBC-treated mice 2, 4 and 8 h post-initiation. A significant reduction in levels of Cyp 1a1, Nqo1 at 8 h and Akr 1c14 mRNA was observed in Cyp 1b1 null (but not wt or het) mice, whereas no impact was observed in Gst a1, Nqo 1 at 2 and 4 h or Akr 1c19 at any time point. Cyp 1b1 mRNA was not elevated by DBC. The major covalent DNA adducts, dibenzo[def,p]chrysene-(±)-11,12-dihydrodiol-cis and trans-13,14-epoxide-deoxyadenosine (DBCDE-dA) were quantified by UHPLC-MS/MS 8 h post-initiation. Loss of Cyp1 b1 expression reduced DBCDE-dA adducts in the skin but not to a statistically significant degree. The ratio of cis- to trans-DBCDE-dA adducts was higher in the skin than other target tissues such as the spleen, lung and liver (oral dosing). These results document that Cyp 1b1 plays a significant role in bioactivation and carcinogenesis of DBC in a two-stage mouse skin tumor model and that loss of Cyp 1b1 has little impact on tumor response with BaP or CTE as initiators. - Highlights: • Cyp1b1 null mice exhibit lower skin cancer sensitivity to DBC but not BaP or CTE. • Cyp1b1 expression impacts expression of other PAH metabolizing enzymes. • cis/trans-DBCDE-dA ratio significantly higher in the skin than the spleen, lung or liver • Potency of DBC and CTE in mouse skin is higher than predicted by RPFs.

  6. Basophils and skin disorders.

    Science.gov (United States)

    Borriello, Francesco; Granata, Francescopaolo; Marone, Gianni

    2014-05-01

    Since their discovery in 1879, basophils have been viewed as circulating blood granulocytes with limited immune function. New research tools for their functional analysis in vivo have revealed previously unrecognized roles for basophils in several skin disorders. Human basophils infiltrate different skin lesions and have been implicated in the pathogenesis of diseases ranging from chronic idiopathic urticaria to systemic lupus erythematosus. In mouse models, basophils participate in IgE-mediated chronic allergic inflammation of the skin and have a protective role in tick infestation. In this review, we discuss critical advances in our understanding of basophil biology and their roles in the pathophysiology of skin disorders.

  7. Skin Diseases: Skin Health and Skin Diseases

    Science.gov (United States)

    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 ...

  8. The prostaglandin receptor EP2 activates multiple signaling pathways and beta-arrestin1 complex formation during mouse skin papilloma development.

    Science.gov (United States)

    Chun, Kyung-Soo; Lao, Huei-Chen; Trempus, Carol S; Okada, Manabu; Langenbach, Robert

    2009-09-01

    Prostaglandin E(2) (PGE(2)) is elevated in many tumor types, but PGE(2)'s contributions to tumor growth are largely unknown. To investigate PGE(2)'s roles, the contributions of one of its receptors, EP2, were studied using the mouse skin initiation/promotion model. Initial studies indicated that protein kinase A (PKA), epidermal growth factor receptor (EGFR) and several effectors-cyclic adenosine 3',5'-monophosphate response element-binding protein (CREB), H-Ras, Src, protein kinase B (AKT) and extracellular signal-regulated kinase (ERK)1/2-were activated in 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted papillomas and that PKA and EGFR inhibition (H89 and AG1478, respectively) decreased papilloma formation. EP2's contributions to the activation of these pathways and papilloma development were determined by inhibiting endogenous TPA-induced PGE(2) production with indomethacin (Indo) and concomitantly treating with the EP2 agonist, CAY10399 (CAY). CAY treatment restored papilloma formation in TPA/Indo-treated mice and increased cyclic adenosine 3',5'-monophosphate and PKA activation as measured by p-CREB formation. CAY treatment also increased EGFR and Src activation and their inhibition by AG1478 and PP2 indicated that Src was upstream of EGFR. CAY also increased H-Ras, ERK1/2 and AKT activation, and AG1478 decreased their activation indicating EGFR being upstream. Supporting EP2's contribution, EP2-/- mice exhibited 65% fewer papillomas and reduced Src, EGFR, H-Ras, AKT and ERK1/2 activation. G protein-coupled receptor (GPCR) activation of EGFR has been reported to involve Src's activation via a GPCR-beta-arrestin-Src complex. Indeed, immunoprecipitation of beta-arrestin1 or p-Src indicated the presence of an EP2-beta-arrestin1-p-Src complex in papillomas. The data indicated that EP2 contributed to tumor formation via activation of PKA and EGFR and that EP2 formed a complex with beta-arrestin1 and Src that contributed to signaling and/or EP2 desensitization.

  9. The prostaglandin receptor EP2 activates multiple signaling pathways and β-arrestin1 complex formation during mouse skin papilloma development

    Science.gov (United States)

    Chun, Kyung-Soo; Lao, Huei-Chen; Trempus, Carol S.; Okada, Manabu; Langenbach, Robert

    2009-01-01

    Prostaglandin E2 (PGE2) is elevated in many tumor types, but PGE2's contributions to tumor growth are largely unknown. To investigate PGE2's roles, the contributions of one of its receptors, EP2, were studied using the mouse skin initiation/promotion model. Initial studies indicated that protein kinase A (PKA), epidermal growth factor receptor (EGFR) and several effectors—cyclic adenosine 3′,5′-monophosphate response element-binding protein (CREB), H-Ras, Src, protein kinase B (AKT) and extracellular signal-regulated kinase (ERK)1/2—were activated in 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted papillomas and that PKA and EGFR inhibition (H89 and AG1478, respectively) decreased papilloma formation. EP2's contributions to the activation of these pathways and papilloma development were determined by inhibiting endogenous TPA-induced PGE2 production with indomethacin (Indo) and concomitantly treating with the EP2 agonist, CAY10399 (CAY). CAY treatment restored papilloma formation in TPA/Indo-treated mice and increased cyclic adenosine 3′,5′-monophosphate and PKA activation as measured by p-CREB formation. CAY treatment also increased EGFR and Src activation and their inhibition by AG1478 and PP2 indicated that Src was upstream of EGFR. CAY also increased H-Ras, ERK1/2 and AKT activation, and AG1478 decreased their activation indicating EGFR being upstream. Supporting EP2's contribution, EP2−/− mice exhibited 65% fewer papillomas and reduced Src, EGFR, H-Ras, AKT and ERK1/2 activation. G protein-coupled receptor (GPCR) activation of EGFR has been reported to involve Src's activation via a GPCR–β-arrestin–Src complex. Indeed, immunoprecipitation of β-arrestin1 or p-Src indicated the presence of an EP2–β-arrestin1–p-Src complex in papillomas. The data indicated that EP2 contributed to tumor formation via activation of PKA and EGFR and that EP2 formed a complex with β-arrestin1 and Src that contributed to signaling and/or EP2

  10. Eosinophil-derived leukotriene C4 signals via type 2 cysteinyl leukotriene receptor to promote skin fibrosis in a mouse model of atopic dermatitis.

    Science.gov (United States)

    Oyoshi, Michiko K; He, Rui; Kanaoka, Yoshihide; ElKhal, Abdallah; Kawamoto, Seiji; Lewis, Christopher N; Austen, K Frank; Geha, Raif S

    2012-03-27

    Atopic dermatitis (AD) skin lesions exhibit epidermal and dermal thickening, eosinophil infiltration, and increased levels of the cysteinyl leukotriene (cys-LT) leukotriene C(4) (LTC(4)). Epicutaneous sensitization with ovalbumin of WT mice but not ΔdblGATA mice, the latter of which lack eosinophils, caused skin thickening, collagen deposition, and increased mRNA expression of the cys-LT generating enzyme LTC(4) synthase (LTC(4)S). Skin thickening and collagen deposition were significantly reduced in ovalbumin-sensitized skin of LTC(4)S-deficient and type 2 cys-LT receptor (CysLT(2)R)-deficient mice but not type 1 cys-LT receptor (CysLT(1)R)-deficient mice. Adoptive transfer of bone marrow-derived eosinophils from WT but not LTC(4)S-deficient mice restored skin thickening and collagen deposition in epicutaneous-sensitized skin of ΔdblGATA recipients. LTC(4) stimulation caused increased collagen synthesis by human skin fibroblasts, which was blocked by CysLT(2)R antagonism but not CysLT(1)R antagonism. Furthermore, LTC(4) stimulated skin fibroblasts to secrete factors that elicit keratinocyte proliferation. These findings establish a role for eosinophil-derived cys-LTs and the CysLT(2)R in the hyperkeratosis and fibrosis of allergic skin inflammation. Strategies that block eosinophil infiltration, cys-LT production, or the CysLT(2)R might be useful in the treatment of AD.

  11. Keratinocyte p38δ loss inhibits Ras-induced tumor formation, while systemic p38δ loss enhances skin inflammation in the early phase of chemical carcinogenesis in mouse skin.

    Science.gov (United States)

    Kiss, Alexi; Koppel, Aaron C; Anders, Joanna; Cataisson, Christophe; Yuspa, Stuart H; Blumenberg, Miroslav; Efimova, Tatiana

    2016-05-01

    p38δ expression and/or activity are increased in human cutaneous malignancies, including invasive squamous cell carcinoma (SCC) and head and neck SCC, but the role of p38δ in cutaneous carcinogenesis has not been well-defined. We have reported that mice with germline loss of p38δ exhibited a reduced susceptibility to skin tumor development compared with wild-type mice in the two-stage 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) chemical skin carcinogenesis model. Here, we report that p38δ gene ablation inhibited the growth of tumors generated from v-ras(Ha) -transformed keratinocytes in skin orthografts to nude mice, indicating that keratinocyte-intrinsic p38δ is required for Ras-induced tumorigenesis. Gene expression profiling of v-ras(Ha) -transformed p38δ-null keratinocytes revealed transcriptional changes associated with cellular responses linked to tumor suppression, such as reduced proliferation and increased differentiation, cell adhesion, and cell communications. Notably, a short-term DMBA/TPA challenge, modeling the initial stages of chemical skin carcinogenesis treatment, elicited an enhanced inflammation in p38δ-null skin compared with skin of wild-type mice, as assessed by measuring the expression of pro-inflammatory cytokines, including IL-1β, IL-6, IL-17, and TNFα. Additionally, p38δ-null skin and p38δ-null keratinocytes exhibited increased p38α activation and signaling in response to acute inflammatory challenges, suggesting a role for p38α in stimulating the elevated inflammatory response in p38δ-null skin during the initial phases of the DMBA/TPA treatment compared with similarly treated p38δ(+/+) skin. Altogether, our results indicate that p38δ signaling regulates skin carcinogenesis not only by keratinocyte cell-autonomous mechanisms, but also by influencing the interaction between between the epithelial compartment of the developing skin tumor and its stromal microenvironment.

  12. Tattooing of skin results in transportation and light-induced decomposition of tattoo pigments--a first quantification in vivo using a mouse model.

    Science.gov (United States)

    Engel, Eva; Vasold, Rudolf; Santarelli, Francesco; Maisch, Tim; Gopee, Neera V; Howard, Paul C; Landthaler, Michael; Bäumler, Wolfgang

    2010-01-01

    Millions of people are tattooed with inks that contain azo pigments. The pigments contained in tattoo inks are manufactured for other uses with no established history of safe use in humans and are injected into the skin at high densities (2.5 mg/cm(2)). Tattoo pigments disseminate after tattooing throughout the human body and although some may photodecompose at the injection site by solar or laser light exposure, the extent of transport or photodecomposition under in vivo conditions remains currently unknown. We investigated the transport and photodecomposition of the widely used tattoo Pigment Red 22 (PR 22) following tattooing into SKH-1 mice. The pigment was extracted quantitatively at different times after tattooing. One day after tattooing, the pigment concentration was 186 microg/cm(2) skin. After 42 days, the amount of PR 22 in the skin has decreased by about 32% of the initial value. Exposure of the tattooed skin, 42 days after tattooing, to laser light reduced the amount of PR 22 by about 51% as compared to skin not exposed to laser light. A part of this reduction is as a result of photodecomposition of PR 22 as shown by the detection of corresponding hazardous aromatic amines. Irradiation with solar radiation simulator for 32 days caused a pigment reduction of about 60% and we again assume pigment decomposition in the skin. This study is the first quantitative estimate of the amount of tattoo pigments transported from the skin into the body or decomposed by solar or laser radiation.

  13. Fluorescence photobleaching of ALA and ALA-heptyl ester induced protoporphyrin IX during photodynamic therapy of normal hairless mouse skin: a comparison of two light sources and different illumination schemes.

    Science.gov (United States)

    Pudroma, Xiao; Juzeniene, Asta; Ma, Li-Wei; Iani, Vladimir; Moan, Johan

    2011-01-01

    This study investigated photobleaching of protoporphyrin IX (PpIX) induced by 5-aminolevulinic acid (ALA) and ALA-heptyl ester during superficial photodynamic therapy (PDT) in normal skin of the female BALB/c-nu/nu athymic mouse. We examined the effects of two light sources (laser and broadband lamp) and two different illumination schemes (fractionated light and continuous irradiation) on the kinetics of photobleaching. Our results show that light exposure (0-30 minutes, 10 mW/cm2) of wavelengths of approximately 420 nm (blue light) and 635 nm (red light) induced time-dependent PpIX photobleaching for mouse skin of 2% ALA and ALA-heptyl ester. Blue light (10 mW/cm2) caused more rapid PpIX photobleaching than did red light (100 mW/cm2), which is attributed to stronger absorption at 407 nm than at 632 nm for PpIX. In the case of light fractionation, fractionated light induced faster photobleaching compared with continuous light exposure after topical application of 2% ALA and ALA-heptyl ester in vivo. These have been suggested to allow reoxygenation of the irradiated tissue, with a consequent enhancement of singlet oxygen production in the second and subsequent fractions.

  14. Your Skin

    Science.gov (United States)

    ... Room? What Happens in the Operating Room? Your Skin KidsHealth > For Kids > Your Skin Print A A ... are really dead skin cells. continue Bye-Bye Skin Cells These old cells are tough and strong, ...

  15. Establishment of Mouse Model of Skin Ischemia%小鼠皮肤局部缺血模型的建立

    Institute of Scientific and Technical Information of China (English)

    黄谢梅; 邢伟; 黄宏; 郝进; 徐祥

    2011-01-01

    Objective To establish the model of acute skin ischemia in Kun Ming mice. Methods Forty female kun Ming mice were divided into A and B two groups randomly,20 in each group . Group A U-shaped peninsular incision,which is 1. 5 cm in width and 3. 3 cm in length, as deep as full thickness, was created on the back of A-group kun Ming mice. Group B U-shaped peninsular incision, which is 1. 5 cm in width and 2. 5 cm in length, as deep as full thickness, was created on the back of the other female kun Ming mice. Before suturing flaps back in place,a 2-mm-wild medical rubber sheet was inserted to separate the flap edges. Then the flaps were observed and the blood flow of flaps were measured by The full-field laser perfusion imager (FLPI; Moor Instruments Ltd). Results 50% of the longer flaps had approximately (37. 20 ± 4. 83) % necrosis on the second postoperative day . All of the longer flaps developed a considerable amount of distal necrosis rate on the third postoperative day,which was increase with time. The smaller flaps displayed cyanosis and edema on the first postoperative day. The area of cyanosis and edema accounted for (77. 46 ± 4. 51) % , and was followed by a progressive decrease over the course of 5 d. Cyanosis , edema completely dissipated until the seventh day. There was a significant decrease in the flap blood flow on the first day after operation ( p <0. 05 ). There was no distinctly significance until the seventh day. Conclusion We have Successfully established a Kun Ming mouse model of skin ischemia,which provided the possibility to investigate the mechanism and strategy of microvascular regeneration.%目的 研究建立稳定的昆明小鼠皮肤局部缺血模型.方法 取40只雌性昆明小鼠,随机分为A/B两组,每组20只.分别在小鼠背部建立深达皮下筋膜层的U型皮瓣.A组为3.3×1.5 cm皮瓣组,B组为2.5×1.5 em皮瓣组.皮瓣游离缘垫以医用橡胶,缝合切口,造成皮肤缺血模型,术后观察皮瓣发绀水肿及

  16. 强脉冲光及射频对BALB/c小鼠皮肤胶原的影响%Effects of intense pulsed light and radiofrequency radiation on the content of collagen in BALB/c mouse skin

    Institute of Scientific and Technical Information of China (English)

    潘敏; 蒋艺

    2012-01-01

    Objective To investigate the effects of intense pulsed light (IPL) and radiofrequency radiation on the appearance,histopathological manifestation,dermal depth and collagen content in BALB/c mouse skin.Methods The back of BALB/c mice was irradiated with intense pulsed light (IPL group,n =9),radiofrequency (RF group,N =9),IPL and radiofrequency (IPL+RF group,n =9) respectively,for 4 sessions at 1-week intervals followed by 2 sessions at 2-week intervals.Three mice remaining untreated served as the control group.The appearance of skin on the back of mice was observed at different time points after irradiation.Some mice were sacrificed and skin specimens were obtained from the back at week 4,8 and 12 after the first irradiation.Hematoxylin and eosin staining was performed to observe the histopathological manifestation and measure the dermal depth of mouse skin,and Masson staining to detect the expression of collagen fiber in mouse skin.Results No local adverse effects were observed in the back skin of mice after irradiation with IPL or radiofrequency.Since the 8th week after the first irradiation,the dermal layer had appeared to be thickened,with an increase in the content of collagen fiber and extraeellular matrix,in the IPL group,RF group and IPL+ RF group compared witb the control group,and the increase was more obvious in the IPL+RF group than in the IPL group and RF group (all P < 0.05 ).Increased collagen fiber was densely arranged in irradiated mice.There was no apparent thickening of skin epidermis after irradiation.Conclusions Both IPL and radiofrequency can stimulate an increase in dermal collagen production in mice,and a synergistic effect exists between IPL and radiofrequency in the biostimulation of collagen synthesis.%目的 探讨强脉冲光和射频对BALB/c小鼠皮肤的外观不良反应、组织病理、真皮厚度变化及胶原含量的影响.方法 将BALB/c小鼠随机分为强脉冲光照射组(IPL组)、射频照射组(RF组)、强脉冲

  17. 毛发生长周期对小鼠皮肤创伤愈合的影响%Impact of hair growth phase on mouse skin wound healing

    Institute of Scientific and Technical Information of China (English)

    孔亚男; 张敏; 崔梦卿; 李良平; 周志涛; 张琳

    2013-01-01

    目的 探讨处于不同毛发生长周期的C57BL/6小鼠皮肤创伤愈合速度.方法 制备小鼠皮肤创伤模型,计算术后0、3、7d创面愈合率,愈合率=(原始创面面积—未愈合的创面面积)/原始创面面积×100%,比较毛发静止期(Hair telogen stages)小鼠和毛发生长期(Hair anagen stages)小鼠伤口愈合速度.采用HE染色比较伤口愈合的组织形态结构差异,利用BrdU检测伤口周围细胞增殖.结果 毛发生长期的小鼠皮肤伤口愈合率显著高于毛发静止期的小鼠伤口愈合率.HE染色显示毛发生长期小鼠伤口周围表皮细胞层较多,且表皮细胞向伤口迁移增强;BrdU检测显示毛发生长期小鼠皮肤伤口周围表皮BrdU+细胞数多于毛发静止期小鼠.结论 毛发生长期的小鼠皮肤创伤愈合率高于毛发静止期小鼠,这—结果为进一步探讨毛囊在创伤愈合过程中的作用提供研究基础,也为选择皮肤创伤愈合动物模型提供指导.%Objective To investigate the skin wound healing speed of C57BL/6 mice at various stages of hair growth cycle.Methods Mouse skin wounding models were established and wound healing rate in the following manner was calculated:Wound closure rate (%) =[(Original wound area-Open area on the final day)/Original wound area] × 100%.Wound healing speed of mouse at hair anagen stages and at hair telogen stages was compared.H&E staining was adopted to compare differences in morphological and histological characteristics of wound healing.BrdU was used to detect cell proliferation around wounds.Results Wound healing rate of mouse at hair anagen stages was significant higher than that of mouse at telogen stages.H&E staining showed that mice presented relatively more epidermal cell layers around wounds and epidermal cell layers migrated faster at hair anagen stages.BrdU detection showed that mice at hair anagen stages had a larger number of BrdU+ epidermal cells around wounds than mouse at telogen

  18. Antibacterial Evaluation of Synthetic Thiazole Compounds In Vitro and In Vivo in a Methicillin-Resistant Staphylococcus aureus (MRSA) Skin Infection Mouse Model.

    Science.gov (United States)

    Mohammad, Haroon; Cushman, Mark; Seleem, Mohamed N

    2015-01-01

    The emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA), including strains resistant to current antibiotics, has contributed to an increase in the number of skin infections reported in humans in recent years. New therapeutic options are needed to counter this public health challenge. The aim of the present study was to examine the potential of thiazole compounds synthesized by our research group to be used topically to treat MRSA skin and wound infections. The broth microdilution method confirmed that the lead thiazole compound and four analogues are capable of inhibiting MRSA growth at concentrations as low as 1.3 μg/mL. Additionally, three compounds exhibited a synergistic relationship when combined with the topical antibiotic mupirocin against MRSA in vitro via the checkerboard assay. Thus the thiazole compounds have potential to be used alone or in combination with mupirocin against MRSA. When tested against human keratinocytes, four derivatives of the lead compound demonstrated an improved toxicity profile (were found to be non-toxic up to a concentration of 20 μg/mL). Utilizing a murine skin infection model, we confirmed that the lead compound and three analogues exhibited potent antimicrobial activity in vivo, with similar capability as the antibiotic mupirocin, as they reduced the burden of MRSA present in skin wounds by more than 90%. Taken altogether, the present study provides important evidence that these thiazole compounds warrant further investigation for development as novel topical antimicrobials to treat MRSA skin infections.

  19. 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.

    Science.gov (United States)

    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) 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.

  20. The alpha/beta carboxy-terminal domains of p63 are required for skin and limb development. New insights from the Brdm2 mouse which is not a complete p63 knockout but expresses p63 gamma-like proteins

    DEFF Research Database (Denmark)

    Wolff, S; Talos, F; Palacios, G;

    2009-01-01

    p63, an ancestral transcription factor of the p53 family, has three C-terminal isoforms whose relative in vivo functions are elusive. The p63 gene is essential for skin and limb development, as vividly shown by two independent global knockout mouse models. Both strains, although constructed diffe...

  1. Skin Conditions

    Science.gov (United States)

    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, ...

  2. 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.

    Science.gov (United States)

    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.

  3. Combinatorial chemopreventive effect of butyric acid, nicotinamide and calcium glucarate against the 7,12-dimethylbenz(a)anthracene induced mouse skin tumorigenesis attained by enhancing the induction of intrinsic apoptotic events.

    Science.gov (United States)

    Tiwari, Prakash; Sahay, Satya; Pandey, Manuraj; Qadri, Syed S Y H; Gupta, Krishna P

    2015-01-25

    We explored the basis of the combinatorial chemopreventive effect of butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG) on mouse skin exposed to 7,12-dimethylbenz(a)anthracene (DMBA). We studied the effects of topical application of DMBA in the presence or absence of BA, NA and CAG on the regulators of apoptosis. DMBA treatment suppressed Bax, Bax/Bcl-2 ratio, release of cyt c, Apaf1, caspase-9, -3 mediated apoptosis. Downregulation of p21 and upregulation of Bcl-2, mut p53 were also observed in only DMBA treated mice. Simultaneous application of BA, NA and CAG induced a mitochondria-mediated apoptosis, characterized by a rise in the Bax, Bax/Bcl-2 ratio, release of cyt c, upregulation of Apaf1 with down-stream activation of caspase-9, -3. Furthermore treatment with BA, NA and CAG demonstrated an upregulation of p21 and downregulation of Bcl-2, mut p53. But this effect was enhanced in the presence of all the three compounds together in combination. Chemoprevention by a combination of BA, NA and CAG by inducing the apoptosis, the natural cell death, suggest the importance of the potential combinational strategies capable of preventing skin tumor development.

  4. Lack of significant skin inflammation during elimination by apoptosis of large numbers of mouse cutaneous mast cells after cessation of treatment with stem cell factor.

    Science.gov (United States)

    Maurer, Marcus; Galli, Stephen J

    2004-12-01

    We previously reported that subcutaneous (s.c.) administration of stem cell factor (SCF), the ligand for the c-Kit receptor, to the back skin of mice promotes marked local increases in the numbers of cutaneous mast cells (MCs), and that cessation of SCF treatment results in the rapid reduction of cutaneous MC populations by apoptosis. In the present study, we used the 125I-fibrin deposition assay, a very sensitive method for quantifying increased vascular permeability, to assess whether the clearance of large numbers of apoptotic MCs is associated with significant cutaneous inflammation. The s.c. injection of rrSCF164 (30 or 100 microg/kg/day) or rrSCF164-peg (polyethylene glycol-treated SCF, 30 or 100 microg/kg/day) for 23 days increased the numbers of dermal MCs at skin injection sites from 5.1+/-0.7 MCs/mm2 to 36.4+/-4.1, 34.7+/-9.7, 52.5+/-5.8, and 545+/-97 MCs/mm2, respectively. In contrast, MC numbers were markedly lower in mice that had been treated with SCF for 21 days, followed by 2 days of injection with the vehicle alone. Notably, when tested during the period of rapid reduction of skin MCs,125I-fibrin deposition in the skin was very similar to that in mice receiving continuous treatment with SCF or vehicle. We conclude that the rapid elimination of even very large populations of MCs by apoptosis, which also results in the clearance of the considerable quantities of proinflammatory products stored by these cells, does not lead to significant local cutaneous inflammatory responses.

  5. Caffeic Acid Inhibits UVB-induced Inflammation and Photocarcinogenesis Through Activation of Peroxisome Proliferator-activated Receptor-γ in Mouse Skin.

    Science.gov (United States)

    Balupillai, Agilan; Prasad, Rajendra N; Ramasamy, Karthikeyan; Muthusamy, Ganesan; Shanmugham, Mohana; Govindasamy, Kanimozhi; Gunaseelan, Srithar

    2015-11-01

    In this study, the effect of caffeic acid (CA) on both acute and chronic UVB-irradiation-induced inflammation and photocarcinogenesis was investigated in Swiss albino mice. Animals were exposed to 180 mJ cm(-2) of UVB once daily for 10 consecutive days and thrice weekly for 30 weeks for acute and chronic study respectively. UVB exposure for 10 consecutive days showed edema formation, increased lipid peroxidation and decreased antioxidant status with activation of inflammatory molecules such as TNF-α, IL-6, COX-2 and NF-κB. However, CA (15 mg per kg.b.wt.) administration before each UVB exposure decreased lipid peroxidation, inflammatory markers expression and enhanced antioxidant status probably through the activation of peroxisome proliferator-activated receptors (PPARγ) in the mice skin. PPARγ is considered a potential target for photochemoprevention because it inhibits UVB-mediated inflammatory responses. In this study, UVB exposure for 30 weeks caused squamous cell carcinoma and upregulation of iNOS, VEGF and TGF-β and downregulation of p53 and tumor incidence in the mice skin. Both topical (CAT) and intraperitoneal (CAIP) treatment before each UVB exposure downregulates iNOS, VEGF, TGF-β, upregulates p53 and reduces tumors multiplicity in the mice skin. Thus, CA offers protection against UVB-induced photocarcinogenesis probably through activation of anti-inflammatory transcription factor PPARγ in the mice.

  6. The effect of multifunctional polymer-based gels on wound healing in full thickness bacteria-contaminated mouse skin wound models.

    Science.gov (United States)

    Yates, Cecelia C; Whaley, Diana; Babu, Ranjith; Zhang, Jianying; Krishna, Priya; Beckman, Eric; Pasculle, A William; Wells, Alan

    2007-09-01

    We determined whether a two-part space-conforming polyethylene glycol/dopa polymer-based gel promoted healing of contaminated wounds in mice. This silver-catalysed gel was previously developed to be broadly microbiocidal in vitro while being biocompatible with human wound cell functioning. Full-thickness wounds were created on the backs of mice. The wounds were inoculated with 10(4) CFU of each of four common skin wound contaminants, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumanii and Clostridium perfringens. The wounds were then treated with our multifunctional polymer-based gel, the commercially available NewSkin product, or left to heal untreated. The untreated wounds were overtly infected, and presented detectable bacterial loads over the entire 21-day healing period, while the gel and NewSkin groups presented significantly smaller rises in bacterial levels and were cleared of detectable colonies by the third week, with the gel group clearing the bacteria earlier. While all three groups healed their wounds, the polymer-based gel-treated group demonstrated significantly earlier re-epithelialization and dermal maturation (Phealing wound. These preclinical studies show that the anti-microbial polymer gel not only supports but also accelerates healing of bacterially contaminated wounds.

  7. UVB exposure enhanced benzanthrone-induced inflammatory responses in SKH-1 mouse skin by activating the expression of COX-2 and iNOS through MAP kinases/NF-κB/AP-1 signalling pathways.

    Science.gov (United States)

    Abbas, Sabiya; Alam, Shamshad; Pal, Anu; Kumar, Mahadeo; Singh, Dhirendra; Ansari, Kausar Mahmood

    2016-10-01

    This study was conducted to explore the role of UVB on benzanthrone (BA)-induced skin inflammation and its mechanism/s. SKH-1 hairless mice were topically exposed with BA (25 and 50 mg/kg b.wt) either alone or along with UVB (50 mJ/cm(2)) for 24 h and estimation of ROS, histopathological analysis, myeloperoxidase (MPO) activity, mast cell staining, immunohistochemistry for COX-2 and iNOS as well as western blotting for MAPKs, p-NF-κB, c-jun, c-fos COX-2 and iNOS were carried out. Enhanced ROS generation, increased epidermal thickness, mast cell number, MPO activity, enhanced expression of COX-2 and iNOS, MAPKs, c-jun, c-fos, NF-κB were found in BA either alone or when followed by UVB treatment, compared to the control groups. Expression of COX-2, iNOS and phosphorylation of ERK1/2 were found to be more enhanced in BA and UVB- exposed group compared to BA and UVB only group, while phosphorylation of JNK1/2, p38, NF-κB and expression of c-jun and c-fos were comparable with BA and UVB only groups. In summary, we suggest that UVB exposure enhanced BA-induced SKH-1 skin inflammation possibly via oxidative stress-mediated activation of MAPKs-NF-κB/AP-1 signalling, which subsequently increased the expression of COX-2 and iNOS and led to inflammation in SKH-1 mouse skin.

  8. Preventive effects of butyric acid, nicotinamide, calcium glucarate alone or in combination during the 7, 12-dimethylbenz (a) anthracene induced mouse skin tumorigenesis via modulation of K-Ras-PI3K-AKTpathway and associated micro RNAs.

    Science.gov (United States)

    Tiwari, Prakash; Sahay, Satya; Pandey, Manuraj; Qadri, Syed S Y H; Gupta, Krishna P

    2016-02-01

    Skin cancer is among the most common cancers worldwide and identifiable molecular changes for early and late stage of skin tumorigenesis can suggest the better targets for its control. In this study, we investigated the status of K-Ras-PI3K-AKTpathway followed by NF-κB, cyclin D1, MMP-9 and regulatory micro RNA during 7, 12-dimethylbenz[a]anthracene (DMBA) induced mouse skin tumorigenesis and its prevention by butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG), individually or in combination with respect to time. DMBA upregulated the K-Ras, PI3K, Akt, NF-κB, cyclin D1 and MMP-9, but downregulated the PTEN in a time dependent manner. DMBA also reduced the levels of micoRNA let-7a but induced the levels of miR-21 and miR-20a as a function of time. BA, NA and CAG were found to prevent DMBA induced changes, but they were most effective when used together in a combination. Reduced let-7a and miR-211 were correlated with the overexpression of K-Ras and MMP-9. Overexpression of miR-21 and miR-20a was correlated with the down regulation of PTEN and overexpression of Cyclin D1. Collectively, the enhanced chemopreventive potential of natural compound in combination via regulation of K-Ras-PI3K-AKTpathway along with regulatory micro RNAs provide a newer and effective mean for cancer management.

  9. 祛斑汤对小鼠皮肤黑素合成影响的研究%Study on the Effect of Qu-ban Decoction On the Melanin Synthesis in Mouse Skin

    Institute of Scientific and Technical Information of China (English)

    李艳; 艾儒棣; 肖桦; 郝平生

    2012-01-01

    To observe the effect of Qu-ban Decoction on melanin synthesis in the female C57BL/6J mouse skin and provide the experimental basis for exploring deeply the mechanism of treating melasma by the prescription. Methods; Female C57BL/ 6J mice were randomly divided into the blank control group, the Qu-ban Decoction low dose group (10 g/kg) , the middle dose group (20 g/kg) , the high dose group (40 g/kg) and the vitamin C group. Take the skin from mice fed with drug for 30 days. Use immu-nohistochemical techniques to observe the melanin distribution and the result was analyzed using the one-way ANOVA statistically. Results : The melanocytes that contained the melanin granules were named positive cells. The average optical densities of positive cells of the high dose group and the middle dose group were lower than the blank control group. The difference between the high dose group, the middle dose group and the blank control group was significant statistically (P <0. 01) . Conclusion; The Qu-ban Decoction can inhibit the melanin synthesis and reduce the melanin distribution in female C57BI/6J mouse skin.%目的:观察祛斑汤对雌性C57BL/6J小鼠皮肤黑素合成的影响,为探索该方剂治疗黄褐斑机制提供实验依据.方法:将雌性C57BL/6J小鼠随机分成空白对照组、祛斑汤低(10 g/kg)、中(20 g/kg)、高剂量(40 g/kg)组、维生素C组.各组灌胃给药30 d后皮肤取材.采用免疫组化法观察小鼠皮肤黑素分布.结果:祛斑汤高、中剂量组黑素颗粒阳性反应的黑素细胞平均光密度低于空白对照组,差别有统计学意义(P<0.01).结论:祛斑汤能抑制雌性C57BI/6J小鼠皮肤中黑素合成、降低黑素分布.

  10. Radiosensitivity of cultured human and mouse keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Parkinson, E.K.; Hume, W.J.; Potten, C.S.

    1986-10-01

    Clonogenic survival assays after ..gamma..-radiation in vitro were performed on freshly isolated and subcultured keratinocytes from mouse skin, mouse tongue and human skin. Survival curves were constructed by fitting the data to a multi-target model of cell survival. When subcultured, keratinocytes from all sites produced survival curves which showed a reduced shoulder region and an increased D/sub 0/ when compared with their freshly isolated counterparts. Freshly isolated human skin keratinocytes were more radiosensitive than mouse keratinocytes from either skin or tongue.

  11. Skin Infections

    Science.gov (United States)

    ... Old Feeding Your 8- to 12-Month-Old Feeding Your 1- to 2-Year-Old First Aid: Skin ... (bacterial infection of the deeper layers of the skin and tissues beneath) are typical childhood skin infections. The usual bacterial culprits in skin ...

  12. miR-206-3p在小鼠皮肤中的表达及其作用%Expression and distribution of miR-206-3p in mouse skin and its potential roles

    Institute of Scientific and Technical Information of China (English)

    穆原; 周红; 李文艳; 李耀武

    2013-01-01

    Objective To investigate the expression and distribution of miR-206-3p and its target gene Bdnf (brain-derived neurotrophic factor) in mouse skin and the potential roles during the development of skin.Methods The full-thickness back skins of BALB/c mice on the 13.5 dpc (day post coition),15.5 dpc,17.5 dpc,1 dpp (day post partum),4 dpp and 16 weeks were collected respectively.The expression levels of miR-206-3p and BdnfmRNA were measured by real time RT-PCR,and BDNF protein was detected by western blot.The distributions of miR-206-3p and BDNF in tissue were profiled by in situ hybridization (ISH) and immunohistochemistry (IHC) respectively.Results The expression level of miR-206-3p increased gradually until 17.5 dpc and subsequently receded to the similar level of the 13.5 dpc during adult stage.The expression of BDNF protein exhibited in the opposite manner of miR-206-3p but BdnfmRNA remained stable from the 17.5 dpc until adult stage.ISH results showed that the distribution of miR-206-3p was gradually regionalized during the development of skin in the postnatal days and mainly located in the suprabasal layer and periphery of hair follicles,which was adjacent to the regions of BDNF expression at the same stage in a nonoverlapping manner.Conclusion The miR-206-3p may be involved in neurodevelopment of mouse skin through the post-transcriptional regulation of Bdnf.%目的 对小鼠皮肤中miR-206-3p及其靶基因脑源性神经营养因子(Bdnf)进行表达与定位检测,以探讨其在皮肤发育过程中的可能作用.方法 手术剪取13.5 dpc(交配后天数)、15.5 dpc、17.5 dpc胎鼠,1 dpp(出生后天数)、4 dpp乳鼠及16周龄雄鼠的背部全层皮肤,用实时荧光定量RT-PCR检测miR-206-3p与Bdnf mRNA的表达水平,western blot检测BDNF蛋白质表达水平,原位杂交与免疫组化分别检测miR-206-3p与BDNF的组织定位.结果 皮肤中miR-206-3p在胚胎期持续升高,到17.5 dpc后逐渐降低,于成年鼠时回复至13.5 dpc时

  13. 5-HT1A/1B receptors as targets for optimizing pigmentary responses in C57BL/6 mouse skin to stress.

    Directory of Open Access Journals (Sweden)

    Hua-Li Wu

    Full Text Available Stress has been reported to induce alterations of skin pigmentary response. Acute stress is associated with increased turnover of serotonin (5-hydroxytryptamine; 5-HT whereas chronic stress causes a decrease. 5-HT receptors have been detected in pigment cells, indicating their role in skin pigmentation. To ascertain the precise role of 5-HT in stress-induced pigmentary responses, C57BL/6 mice were subjected to chronic restraint stress and chronic unpredictable mild stress (CRS and CUMS, two models of chronic stress for 21 days, finally resulting in abnormal pigmentary responses. Subsequently, stressed mice were characterized by the absence of a black pigment in dorsal coat. The down-regulation of tyrosinase (TYR and tyrosinase-related proteins (TRP1 and TRP2 expression in stressed skin was accompanied by reduced levels of 5-HT and decreased expression of 5-HT receptor (5-HTR system. In both murine B16F10 melanoma cells and normal human melanocytes (NHMCs, 5-HT had a stimulatory effect on melanin production, dendricity and migration. When treated with 5-HT in cultured hair follicles (HFs, the increased expression of melanogenesis-related genes and the activation of 5-HT1A, 1B and 7 receptors also occurred. The serum obtained from stressed mice showed significantly decreased tyrosinase activity in NHMCs compared to that from nonstressed mice. The decrease in tyrosinase activity was further augmented in the presence of 5-HTR1A, 1B and 7 antagonists, WAY100635, SB216641 and SB269970. In vivo, stressed mice received 5-HT precursor 5-hydroxy-l-tryptophan (5-HTP, a member of the class of selective serotonin reuptake inhibitors (fluoxetine; FX and 5-HTR1A/1B agonists (8-OH-DPAT/CP94253, finally contributing to the normalization of pigmentary responses. Taken together, these data strongly suggest that the serotoninergic system plays an important role in the regulation of stress-induced depigmentation, which can be mediated by 5-HT1A/1B receptors. 5-HT

  14. Skin Biomes.

    Science.gov (United States)

    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.

  15. 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.

    Science.gov (United States)

    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.

  16. Lupeol induces p53 and cyclin-B-mediated G2/M arrest and targets apoptosis through activation of caspase in mouse skin.

    Science.gov (United States)

    Nigam, Nidhi; Prasad, Sahdeo; George, Jasmine; Shukla, Yogeshwer

    2009-04-03

    Lupeol, present in fruits and medicinal plants, is a biologically active compound that has been shown to have various pharmacological properties in experimental studies. In the present study, we demonstrated the modulatory effect of lupeol on 7,12-dimethylbenz[a]anthracene (DMBA)-induced alterations on cell proliferation in the skin of Swiss albino mice. Lupeol treatment showed significant (p < 0.05) preventive effects with marked inhibition at 48, 72, and 96 h against DMBA-mediated neoplastic events. Cell-cycle analysis showed that lupeol-induced G2/M-phase arrest (16-37%) until 72 h, and these inhibitory effects were mediated through inhibition of the cyclin-B-regulated signaling pathway involving p53, p21/WAF1, cdc25C, cdc2, and cyclin-B gene expression. Further lupeol-induced apoptosis was observed, as shown by an increased sub-G1 peak (28%) at 96 h, with upregulation of bax and caspase-3 genes and downregulation of anti-apoptotic bcl-2 and survivin genes. Thus, our results indicate that lupeol has novel anti-proliferative and apoptotic potential that may be helpful in designing strategies to fight skin cancer.

  17. Pharmacological coal tar induces G:C to T:A transversion mutations in the skin of Muta{trademark} mouse

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, U.; Thein, N.; Moller, P.; Wallin, H. [National Institute of Occupational Health, Copenhagen (Denmark)

    2001-07-01

    Coal tar is a by-product of the distillation of coal. It consists of a complex chemical mixture of aromatic and aliphatic hydrocarbons, with high concentrations of polycyclic aromatic hydrocarbons such as benzo(a)pyrene. It has previously been shown that single painting on skin of mice increases the mutation frequency 16 times in murine epidermis cells. Here, the mutations by DNA sequencing are determined. Coal tar was found to primarily induce G:C to T:A transversions and one-base pair deletions of G:C base pairs. More than half of the mutations were at CpG sites. The mutational spectrum is in agreement with that of benzo(a)pyrene and other polycyclic aromatic hydrocarbon mixtures.

  18. Modulation of miR-203 and its regulators as a function of time during the development of 7, 12 dimethylbenz [a] anthracene induced mouse skin tumors in presence or absence of the antitumor agents

    Energy Technology Data Exchange (ETDEWEB)

    Tiwari, Prakash; Gupta, Krishna P., E-mail: krishnag522@yahoo.co.in

    2014-07-15

    We investigated the chemopreventive effects of naturally occurring compounds like butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG) individually or in combination in 7, 12-dimethylbenz [a] anthracene (DMBA) treated mouse skin at 4 and 16 weeks, the time before and after the tumor development. DMBA application did not show any skin tumors at 4 weeks but well defined tumors appeared at 16 weeks. BA, NA or CAG prevented the tumor development significantly but the protection was highly enhanced when all these compounds were given together. In order to see the molecular changes progressing with tumors, we showed the downregulation of tumor suppressor miR-203 at 16 weeks and upregulation of histone deacetylases (HDAC), DNA methyltransferase, promoter methylation of miR-203 at 4 or 16 weeks. Regulators of micro RNA biogenesis such as DICER1 and Ago2 were also deregulated by DMBA. Proto-oncogene c-myc and BMI1 were upregulated and tumor suppressor gene p16 was downregulated by DMBA as a function of time. Effects of BA, NA or CAG were more pronounced after 16 weeks as compared to 4 weeks in preventing the tumor development and altered gene expression. Concomitant administration of BA, NA and CAG tried to prevent these alterations more effectively than that of individual compound possibly by regulating miR-203 status through epigenetic or biogenetic modulations before and after the tumor development. Study provides a rationale for chemoprevention by combination of different compounds targeting miR-203. - Highlights: • DMBA modulates miR-203 and its regulator before and after the onset of tumors. • Suppression of miR-203 and p16 could be the result of gene promoter methylation. • BA, NA or CAG prevents the effects of DMBA. • Combination of BA, NA or CAG is more effective in preventing the DMBA modulations.

  19. Studies on transdermal delivery of sinomenine hydrochloride through mouse skin treated by microneedle arrays%盐酸青藤碱在微针阵列作用下的透皮给药研究

    Institute of Scientific and Technical Information of China (English)

    李伟泽; 闫菁华; 赵宁; 刘少静

    2011-01-01

    目的 探索盐酸青藤碱在微针阵列作用下的透皮给药规律与微针促进药物透皮吸收的机制.方法 高效液相色谱法测定青藤碱的含量,裸鼠皮肤用微针阵列预刺处理,采用水平双室扩散池法研究微针的针尖形状、刺入力、滞留时间以及阵列数对于盐酸青藤碱透皮给药的影响规律.将微针预刺处理的皮肤制备成切片,并用显微镜观察皮肤的变化.结果 微针阵列预刺处理与被动扩散比较能显著提高盐酸青藤碱透皮给药的累积渗透量(P<0.01),但平顶微针比尖顶微针更能有效促进药物的透皮吸收;药物的累积渗透量随着微针处理皮肤的刺入力的增加而增加,但当刺入力超过5.0 N时,药物的累积渗透量不再显著增加;随着微针在皮肤中滞留时间的延长药物的累积渗透量不断增大,当滞留时间超过60 s时药物的累积渗透量不再显著增加;尽管药物的累积渗透量随着微针阵列数的增加而增加,但是二者之间无正向线性关系.皮肤切片表明微针刺入皮肤后能够在皮肤上形成跨越角质层的微孔道.结论 微针可以在皮肤上形成微孔道而增强皮肤对药物的渗透性,从而为盐酸青藤碱透皮给药系统提供一种新型、高效的透皮给药新技术,具有广泛的应用前景.%Objective To study the characteristics and mechanism of transdermal delivery of sinomenine hydrochloride (SH) through mouse skin treated by solid silicon microneedle arrays. Methods The amount of SH was determined by HPLC system. Hairless rat skin was pretreated with microneedle arrays. The side-by-side diffusion cell method was used to investigate the effects of needlepoint shape, different insertion forces, retention time, and number of microneedlea on transdennal SH delivery. Skin samples treated by microneedles were made into paraffin sections for histological examination and were viewed by brightfield microscopy. Results The skin pretreated

  20. Skin Cancer

    Science.gov (United States)

    ... are round and lie directly under squamous cells. Melanocytes are specialized skin cells that produce pigment called melanin. The melanin pigment produced by melanocytes gives skin its color. It also protects the ...

  1. Skin Cancer

    Science.gov (United States)

    ... the head, face, neck, hands, and arms. Another type of skin cancer, melanoma, is more dangerous but less common. Anyone ... cancer is found early. If not treated, some types of skin cancer cells can spread to other tissues and organs. ...

  2. Sagging Skin

    Science.gov (United States)

    ... Dermatologic Surgery Expertise for the life of your skin (TM) Public Resources Dermatologic Surgery Conditions Treatments and ... learn-more"> 3 million Americans are diagnosed with skin cancer every year Any suspicious new growths or ...

  3. Skin tears.

    Science.gov (United States)

    Baranoski, S

    2001-08-01

    Skin tears are a serious, painful problem for older patients. Find out how your staff can recognize patients at risk, what they can do to prevent skin tears, and how to manage them effectively if they occur.

  4. Skin turgor

    Science.gov (United States)

    ... arm or abdomen is checked. The skin is held for a few seconds then released. Skin with ... University of Washington, Seattle, WA. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the ...

  5. Mouse Prkar1a haploinsufficiency leads to an increase in tumors in the Trp53+/− or Rb1+/− backgrounds and chemically induced skin papillomas by dysregulation of the cell cycle and Wnt signaling

    Science.gov (United States)

    Almeida, Madson Q.; Muchow, Michael; Boikos, Sosipatros; Bauer, Andrew J.; Griffin, Kurt J.; Tsang, Kit Man; Cheadle, Chris; Watkins, Tonya; Wen, Feng; Starost, Matthew F.; Bossis, Ioannis; Nesterova, Maria; Stratakis, Constantine A.

    2010-01-01

    PRKAR1A inactivation leads to dysregulated cAMP signaling and Carney complex (CNC) in humans, a syndrome associated with skin, endocrine and other tumors. The CNC phenotype is not easily explained by the ubiquitous cAMP signaling defect; furthermore, Prkar1a+/− mice did not develop skin and other CNC tumors. To identify whether a Prkar1a defect is truly a generic but weak tumorigenic signal that depends on tissue-specific or other factors, we investigated Prkar1a+/− mice when bred within the Rb1+/− or Trp53+/− backgrounds, or treated with a two-step skin carcinogenesis protocol. Prkar1a+/− Trp53+/− mice developed more sarcomas than Trp53+/− mice (P < 0.05) and Prkar1a+/− Rb1+/− mice grew more (and larger) pituitary and thyroid tumors than Rb1+/− mice. All mice with double heterozygosity had significantly reduced life-spans compared with their single-heterozygous counterparts. Prkar1a+/− mice also developed more papillomas than wild-type animals. A whole-genome transcriptome profiling of tumors produced by all three models identified Wnt signaling as the main pathway activated by abnormal cAMP signaling, along with cell cycle abnormalities; all changes were confirmed by qRT–PCR array and immunohistochemistry. siRNA down-regulation of Ctnnb1, E2f1 or Cdk4 inhibited proliferation of human adrenal cells bearing a PRKAR1A-inactivating mutation and Prkar1a+/− mouse embryonic fibroblasts and arrested both cell lines at the G0/G1 phase of the cell cycle. In conclusion, Prkar1a haploinsufficiency is a relatively weak tumorigenic signal that can act synergistically with other tumor suppressor gene defects or chemicals to induce tumors, mostly through Wnt-signaling activation and cell cycle dysregulation, consistent with studies in human neoplasms carrying PRKAR1A defects. PMID:20080939

  6. Up-regulation of clusterin during phthalocyanine 4 photodynamic therapy-mediated apoptosis of tumor cells and ablation of mouse skin tumors.

    Science.gov (United States)

    Kalka, K; Ahmad, N; Criswell, T; Boothman, D; Mukhtar, H

    2000-11-01

    Photodynamic therapy (PDT) using the silicon phthalocyanine photo-sensitizer Pc 4 is an oxidative stress associated with the induction of apoptosis in many cancer cells in vitro and in vivo. The mechanisms of PDT-induced tumor cell killing leading to apoptosis are incompletely understood. Clusterin, a widely expressed glycoprotein, is induced in tissues regressing as a consequence of oxidative stress-mediated cell death. Treatment of apoptosis-sensitive human epidermoid carcinoma cells (A431) with PDT resulted in significant up-regulation of clusterin with a maximum at 12 h after treatment, whereas clusterin levels in Pc 4-PDT-treated, apoptosis-resistant, radiation-induced fibrosarcoma (RIF-1) cells remained unchanged. The i.v. administration of Pc 4 to mice bearing chemically or UVB radiation-induced skin papillomas, followed by light application, led to increased clusterin protein expression, peaking 24 h after the treatment, when tumor regression was apparently visible. These data, for the first time, demonstrate the involvement of clusterin in PDT-mediated cell death and during tumor regression. This may have relevance in improving the efficacy of PDT using pharmacological inducers of clusterin.

  7. Skin Aging

    Science.gov (United States)

    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 ...

  8. Periostin in Skin Tissue Skin-Related Diseases

    Directory of Open Access Journals (Sweden)

    Yukie Yamaguchi

    2014-01-01

    Recently, periostin—a matricellular protein—has been highlighted for its pivotal functions in the skin. Analysis of periostin null mice has revealed that periostin contributes to collagen fibrillogenesis, collagen cross-linking, and the formation of ECM meshwork via interactions with other ECM components. Periostin expression is enhanced by mechanical stress or skin injury; this is indicative of the physiologically protective functions of periostin, which promotes wound repair by acting on keratinocytes and fibroblasts. Along with its physiological functions, periostin plays pathogenic roles in skin fibrosis and chronic allergic inflammation. In systemic sclerosis (SSc patients, periostin levels reflect the severity of skin fibrosis. Periostin null mice have shown reduced skin fibrosis in a bleomycin-induced SSc mouse model, indicating a key role of periostin in fibrosis. Moreover, in atopic dermatitis (AD, attenuated AD phenotype has been observed in periostin null mice in a house dust mite extract-induced AD mouse model. Th2 cytokine-induced periostin acts on keratinocytes to produce inflammatory cytokines that further enhance the Th2 response, thereby sustaining and amplifying chronic allergic inflammation. Thus, periostin is deeply involved in the pathogenesis of AD and other inflammation-related disorders affecting the skin. Understanding the dynamic actions of periostin would be key to dissecting pathogenesis of skin-related diseases and to developing novel therapeutic strategies.

  9. Application of a fuzzy neural network model in predicting polycyclic aromatic hydrocarbon-mediated perturbations of the Cyp1b1 transcriptional regulatory network in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Larkin, Andrew [Department of Environmental and Molecular Toxicology, Oregon State University (United States); Department of Statistics, Oregon State University (United States); Superfund Research Center, Oregon State University (United States); Siddens, Lisbeth K. [Department of Environmental and Molecular Toxicology, Oregon State University (United States); Superfund Research Center, Oregon State University (United States); Krueger, Sharon K. [Superfund Research Center, Oregon State University (United States); Linus Pauling Institute, Oregon State University (United States); Tilton, Susan C.; Waters, Katrina M. [Superfund Research Center, Oregon State University (United States); Computational Biology and Bioinformatics Group, Pacific Northwest National Laboratory, Richland, WA 99352 (United States); Williams, David E., E-mail: david.williams@oregonstate.edu [Department of Environmental and Molecular Toxicology, Oregon State University (United States); Superfund Research Center, Oregon State University (United States); Linus Pauling Institute, Oregon State University (United States); Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States); Baird, William M. [Department of Environmental and Molecular Toxicology, Oregon State University (United States); Superfund Research Center, Oregon State University (United States); Environmental Health Sciences Center, Oregon State University, Corvallis, OR 97331 (United States)

    2013-03-01

    Polycyclic aromatic hydrocarbons (PAHs) are present in the environment as complex mixtures with components that have diverse carcinogenic potencies and mostly unknown interactive effects. Non-additive PAH interactions have been observed in regulation of cytochrome P450 (CYP) gene expression in the CYP1 family. To better understand and predict biological effects of complex mixtures, such as environmental PAHs, an 11 gene input-1 gene output fuzzy neural network (FNN) was developed for predicting PAH-mediated perturbations of dermal Cyp1b1 transcription in mice. Input values were generalized using fuzzy logic into low, medium, and high fuzzy subsets, and sorted using k-means clustering to create Mamdani logic functions for predicting Cyp1b1 mRNA expression. Model testing was performed with data from microarray analysis of skin samples from FVB/N mice treated with toluene (vehicle control), dibenzo[def,p]chrysene (DBC), benzo[a]pyrene (BaP), or 1 of 3 combinations of diesel particulate extract (DPE), coal tar extract (CTE) and cigarette smoke condensate (CSC) using leave-one-out cross-validation. Predictions were within 1 log{sub 2} fold change unit of microarray data, with the exception of the DBC treatment group, where the unexpected down-regulation of Cyp1b1 expression was predicted but did not reach statistical significance on the microarrays. Adding CTE to DPE was predicted to increase Cyp1b1 expression, whereas adding CSC to CTE and DPE was predicted to have no effect, in agreement with microarray results. The aryl hydrocarbon receptor repressor (Ahrr) was determined to be the most significant input variable for model predictions using back-propagation and normalization of FNN weights. - Highlights: ► Tested a model to predict PAH mixture-mediated changes in Cyp1b1 expression ► Quantitative predictions in agreement with microarrays for Cyp1b1 induction ► Unexpected difference in expression between DBC and other treatments predicted ► Model predictions

  10. Your Skin

    Science.gov (United States)

    ... your body. Without skin, people's muscles, bones, and organs would be hanging out all over the place. Skin holds everything together. It also: protects our bodies helps keep our bodies at just the right temperature allows us to have the sense of touch Don't Miss Your Epidermis The ...

  11. Oily skin

    Science.gov (United States)

    ... keep your skin clean using warm water and soap, or a soapless cleanser. Clean your face with astringent pads if frequent face washing causes irritation. Use only water-based or oil-free cosmetics if you have oily skin. Your ...

  12. Investigation of skin cancer treatment efficiency by raman spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, M. S.; Kim, D. W. [Kyungpook National University, Taegu (Korea)

    2000-04-01

    From the successful perform of the molecular structures of various kinds of human skin cancer. We can predict the types of cancer when a small abnormal change change occurs on skin by raman spectrum. When we applied the cancer causing chemicals, bezopyrene, to nude mouse, it did not develop to cancer. But we had radiated UV light after developed to skin cancer in a few days. We can deduce the development of human skin cancer from the result of nude mouse skin cancer, because the two skin are structurally very similar to each other. From the results of own research we could conform the UV light is essential for the development of skin cancer. The results of own research can be directly apply to early detection and proper treatment of skin cancer in hospital. 32 refs., 40 figs., 16 tabs. (Author)

  13. Aging skin.

    Science.gov (United States)

    Bolognia, J L

    1995-01-16

    Aging of the skin is a composite of actinic damage, chronologic aging, and hormonal influences. The majority of changes associated with aging, such as wrinkles and solar lentigines ("liver spots"), are due to photoaging and reflect cumulative sun exposure as well as skin pigmentation. Classically, chronologic aging includes those cutaneous changes that occur in non-sun-exposed areas, such as the buttocks, and are observed in both men and women. A clinical example would be soft tissue sagging due to elastic fiber degeneration. In women, investigations into the effect of hormones on aging of the skin have concentrated on estrogens; in men, there have been a limited number of studies on the influence of testosterone. The latter have shown an age-dependent decrease in tissue androgens in pubic skin, but not scrotal or thigh skin. To date, age has not been shown to have an effect on androgen receptor binding, although a decrease in foreskin 5 alpha-reductase activity with increasing age has been described. In fibroblast cultures from foreskins, there have been conflicting results as to whether 5 alpha-reductase activity decreases in an age-dependent manner. Some of the skin changes that have been categorized as secondary to chronologic aging, such as decreased sebaceous gland activity and decreased hair growth, may actually represent a decline in the concentration of tissue androgens with increasing age. The influence of androgens on age-related changes in keratinocyte and fibroblast function remains speculative.

  14. 中药大青叶、黄柏、龙胆草对小鼠皮肤炎症反应的影响%Effects of folium isatidis, phellodendron, gentian on skin inflammation of mouse models

    Institute of Scientific and Technical Information of China (English)

    李中辉; 魏跃钢

    2015-01-01

    Objective:To determine the effects of folium isatidis, phellodendron, gentian on skin inflam-mation of mouse allergic contact dermatitis models. Methods: The models of contact dermatitis were induced by FITC 1% (acetone∶DBP 1∶1). The effects of different drugs, including folium isatidis, phellodendron, gentian, saline and dexamethasone on murine ear swelling and histopathological changes were assessed. Saline was used as control. Results:Compared with saline group, the ears swelling and inflammation was markedly suppressed in the folium isatidis group, phellodendron, gentian group and dexamethasone group (P<0.05). Conclusion:Folium isatidis, phellodendron, gentian and dexamethasone have equivalent effect in restraining the inflammation reaction.%目的::明确大青叶、黄柏、龙胆草对小鼠变应性接触性皮炎组织的影响。方法:利用1%FITC(丙酮∶DBP 1∶1)诱发的小鼠变应性接触性皮炎动物模型,将小鼠按给药不同分为空白对照组、生理盐水组、地塞米松组、大青叶组、黄柏组、龙胆草组,通过测量耳厚度差和观察耳朵组织病理改变。结果:大青叶组、黄柏组、龙胆草组、地塞米松组小鼠耳厚度差均明显低于生理盐水组,且它们的耳朵皮肤的炎症反应抑制明显。结论:大青叶、黄柏、龙胆草在抑制急性接触性皮炎的炎症反应方面具有与糖皮质激素相似的效果。

  15. Skin Cancer Prevention

    Science.gov (United States)

    ... Genetics of Skin Cancer Skin Cancer Screening Research Skin Cancer Prevention (PDQ®)–Patient Version What is prevention? ... prevent cancer are being studied. General Information About Skin Cancer Key Points Skin cancer is a disease ...

  16. Skin Cancer Screening

    Science.gov (United States)

    ... Genetics of Skin Cancer Skin Cancer Screening Research Skin Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Skin Cancer Key Points Skin cancer is a disease ...

  17. Dry Skin (Xerosis)

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Dry skin Overview Dry, ashy skin: People who had atopic ... often have very dry skin as adults. Dry skin: Overview Also called xerosis Dry skin is common. ...

  18. A skin-inspired organic digital mechanoreceptor

    Science.gov (United States)

    Tee, Benjamin C.-K.; Chortos, Alex; Berndt, Andre; Nguyen, Amanda Kim; Tom, Ariane; McGuire, Allister; Lin, Ziliang Carter; Tien, Kevin; Bae, Won-Gyu; Wang, Huiliang; Mei, Ping; Chou, Ho-Hsiu; Cui, Bianxiao; Deisseroth, Karl; Ng, Tse Nga; Bao, Zhenan

    2015-10-01

    Human skin relies on cutaneous receptors that output digital signals for tactile sensing in which the intensity of stimulation is converted to a series of voltage pulses. We present a power-efficient skin-inspired mechanoreceptor with a flexible organic transistor circuit that transduces pressure into digital frequency signals directly. The output frequency ranges between 0 and 200 hertz, with a sublinear response to increasing force stimuli that mimics slow-adapting skin mechanoreceptors. The output of the sensors was further used to stimulate optogenetically engineered mouse somatosensory neurons of mouse cortex in vitro, achieving stimulated pulses in accordance with pressure levels. This work represents a step toward the design and use of large-area organic electronic skins with neural-integrated touch feedback for replacement limbs.

  19. The effects of X-rays on the mitotic activity of mouse epidermis

    Energy Technology Data Exchange (ETDEWEB)

    Knowlton, N.P. Jr.; Hempelmann, L.H.; Hoffman, J.G.

    1949-04-19

    This report describes a simplified technique of obtaining the mitotic index of mouse skin and indicates the surprising sensitivity of the mitotic activity of mouse epithelium to the effects of x-rays.

  20. Skin Cancer

    Science.gov (United States)

    ... you ever get a bad sunburn that caused blisters when you were a child?Does your skin ... Cancer InstituteMelanoma International FoundationAmerican Cancer Society ResourcesDiagnosis and Management of Malignant Melanoma by BG Goldstein, AO Goldstein( ...

  1. Squamous cell skin cancer

    Science.gov (United States)

    ... that reflect light more, such as water, sand, concrete, and areas that are painted white. The higher ... - skin - squamous cell; Skin cancer - squamous cell; Nonmelanoma skin cancer - squamous ...

  2. Skin Cancer Foundation

    Science.gov (United States)

    ... Host a Fundraising Event | About Us | Store The Skin Cancer Foundation The Skin Cancer Foundation is the ... A "Sunscreen Gene"? Skin Cancer Facts & Statistics The Skin Cancer Foundation's Champions for Change Gala 2016 Learn ...

  3. Skin Pigmentation Disorders

    Science.gov (United States)

    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 ...

  4. Skin Bleaching

    OpenAIRE

    Ahmed, Samira M.

    2015-01-01

    In this project, I aim to investigate the reasoning behind the practice of skin bleaching by analyzing the documentary ”Dark Girls”, to gain a better understanding of race and colorism issues. Also this project tries to see if there is a connection with history and if this has been a part of making the european beauty ideal determine the choices black’s make in regards to beauty.

  5. TSLP is differentially regulated by vitamin D3 and cytokines in human skin

    OpenAIRE

    Landheer, Janneke; Giovannone, Barbara; Sadekova, Svetlana; Tjabringa, Sandra; Hofstra, Claudia; Dechering, Koen; Bruijnzeel-Koomen, Carla; Chang, Charlie; Ying, Yu; de Waal Malefyt, Rene; Hijnen, DirkJan; Knol, Edward

    2015-01-01

    Thymic stromal lymphopoietin (TSLP) plays an important role in allergic diseases and is highly expressed in keratinocytes in human lesional atopic dermatitis (AD) skin. In nonlesional AD skin TSLP expression can be induced by applying house dust mite allergen onto the skin in the atopy patch test. Several studies have demonstrated that the induction of TSLP expression in mouse skin does not only lead to AD-like inflammation of the skin, but also predisposes to severe inflammation of the airwa...

  6. Autoinflammatory Skin Disorders: The Inflammasomme in Focus.

    Science.gov (United States)

    Gurung, Prajwal; Kanneganti, Thirumala-Devi

    2016-07-01

    Autoinflammatory skin disorders are a group of heterogeneous diseases that include diseases such as cryopyrin-associated periodic syndrome (CAPS) and familial Mediterranean fever (FMF). Therapeutic strategies targeting IL-1 cytokines have proved helpful in ameliorating some of these diseases. While inflammasomes are the major regulators of IL-1 cytokines, inflammasome-independent complexes can also process IL-1 cytokines. Herein, we focus on recent advances in our understanding of how IL-1 cytokines, stemming from inflammasome-dependent and -independent pathways are involved in the regulation of skin conditions. Importantly, we discuss several mouse models of skin inflammation generated to help elucidate the basic cellular and molecular effects and modulation of IL-1 in the skin. Such models offer perspectives on how these signaling pathways could be targeted to improve therapeutic approaches in the treatment of these rare and debilitating inflammatory skin disorders.

  7. Cutaneous skin tag

    Science.gov (United States)

    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 ...

  8. Burn mouse models

    DEFF Research Database (Denmark)

    Calum, Henrik; Høiby, Niels; Moser, Claus

    2014-01-01

    Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third-degree b......Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6 % third......-degree burn injury was induced with a hot-air blower. The third-degree burn was confirmed histologically. At 48 h, a decline in the concentration of peripheral blood leucocytes was observed in the group of mice with burn wound. The reduction was ascribed to the decline in concentration of polymorphonuclear...... neutrophil leucocytes and monocytes. When infecting the skin with Pseudomonas aeruginosa, a dissemination of bacteria was observed only in the burn wound group. Histological characterization of the skin showed an increased polymorphonuclear neutrophil granulocytes dominated inflammation in the group of mice...

  9. Specific unresponsiveness to skin allografts in burns.

    Science.gov (United States)

    Clark, G T; Moon, D J; Cunningham, P R; Johnson, T D; Thomas, J M; Thomas, F T

    1989-05-01

    We have examined the potential to provide long-term or even permanent wound coverage in a mouse model of a 30% total body surface area burn using skin allografts. Treatment of the recipient mouse with rabbit anti-mouse thymocyte serum (ATS) followed by donor bone marrow infusion induces a state of specific unresponsiveness to the skin allograft without the need for chronic immunosuppression. Specifically, a B6AF1 mouse receives a burn on Day -2 relative to grafting, ATS on Day -1, and Day +2, a skin allograft from a C3H/He mouse on Day 0, and infusion of C3H/He donor bone marrow on Day +6. We studied three groups of burned mice: Group I, allograft control (n = 5); Group II, allograft plus ATS (n = 12); and Group III, allograft plus ATS and bone marrow infusion (n = 15). Mean graft survival was compared using a one-way analysis of variance and a Student-Newman-Keuls post hoc test. There was no statistical difference in animal mortality among any of the three groups, and there was no evidence of infectious morbidity. Mean skin allograft survival was as follows: Group I, 9 days; Group II, 29 days; and Group III, 66 days (P less than 0.05 vs Group I and II). Nine animals in Group III had intact hair bearing grafts at 90 days when the study was terminated. This study suggests the potential use of induced specific unresponsiveness to skin allografts for wound coverage in thermal injury without use of chronic immunosuppression. In our animal study this was accomplished without increased mortality or apparent infectious morbidity.

  10. Skin Keratins.

    Science.gov (United States)

    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.

  11. κ-卡拉胶寡糖对小鼠皮肤成纤维细胞增殖和胶原分泌的影响%Effects of κ-carrageenan oligosaccharides on cell proliferation and collagen secretion in cultured mouse skin fibroblast

    Institute of Scientific and Technical Information of China (English)

    王天琦; 吴海歌; 姚子昂

    2013-01-01

    目的研究κ-卡拉胶寡糖对小鼠皮肤成纤维细胞增殖和胶原分泌的影响.方法原代培养小鼠皮肤成纤维细胞,传代培养后加入不同浓度的κ-卡拉胶寡糖作用,应用细胞计数法,四甲基偶氮唑盐(MTT)比色法,检测κ--卡拉胶寡糖对皮肤成纤维细胞增殖的影响,ELISA法检测κ--卡拉胶寡糖对皮肤成纤维细胞分泌Ⅰ型、Ⅲ型胶原蛋白的影响.结果12.5μg/mL~100μg,/mL范围内,各组κ-卡拉胶寡糖对小鼠皮肤成纤维细胞均有一定促进增殖作用,其中以100μg/mL时最为显著(P<0.01).用25μg/mL和50μg/mLκ-卡拉胶寡糖处理小鼠皮肤成纤维细胞后,与对照组相比,Ⅰ型胶原蛋白分泌明显增加(P<0.05);12.5μg/mL~100μg/mL范围内,各组κ-卡拉胶寡糖均显著促进Ⅲ型胶原蛋白分泌(P<0.05).结论κ-卡拉胶寡糖能有效促进小鼠皮肤成纤维细胞增殖和胶原分泌.%Objective: To investigate the effect of κ - carrageenan oligosaccharides on cell proliferation and collagen secretion in cultured mouse skin fibroblasts. Methods; The primary mouse skin fibroblasts were isolated and cultured in vitro. The cells were treated with κ- carrageenan oligosaccharides in different concentration in exponential phase of cell growth. The cell proliferation was measured by cell counting and MTT colormetric assay. Type I and type IE collagen secretion was detected by ELJSA. Results: Compared with the control group,the growth of mouse skin fibroblasts was enhanced. When the cells were stimulated by κ- carrageenan oligosaccharides,100μg/mL is most significant (P < 0.01). Type Ⅰ collagen secretion was increased (P<0.05) after the cells were stimulated by 25μg/mL and 50μg/mL κ - carrageenan oligosaccharides; type Ⅲ collagen secretion was increased ( P < 0. 05) after the cells were stimulated by k - carrageenan oligosaccharides. Conclusion: κ - carrageenan oligosaccharides can enhance the growth of mouse skin fibroblasts and

  12. Induction of anti-EBNA-1 protein by 12-O-tetradecanoylphorbol-13-acetate treatment of human lymphoblastoid cells

    Energy Technology Data Exchange (ETDEWEB)

    Wen, Longthung; Tanaka, Akiko; Nonoyama, Meihan (Showa Univ. Research Institute for Biomedicine in Florida, St. Petersburg (USA))

    1989-08-01

    Binding of the Epstein-Barr virus (EBV) nuclear antigen (EBNA-1) to BamHI-C DNA was studied by affinity column chromatography followed by immunoblotting with human serum specific for EBNA-1. Two species of EBNA-1 (68 and 70 kilodaltons) were identified in nuclear extracts of the EBV-positive Burkitt's lymphoma cell line Raji and not in nuclear extracts of the EBV-negative Burkitt's lymphoma cell line BJAB. Both EBNA-1s bound specifically to the region required for EBV plasmid DNA maintenance (oriP) located in the BamHI-C fragment. Upon treatment with 12-O-tetradecanoylphorbol-13-acetate, which activates latent EBV genome in Raji cells, the 68-kilodalton EBNA-1 was uncoupled from binding to EBV oriP. Nuclear extracts from 12-O-tetradecanoylphorbol-13-acetate-treated BJAB cells also uncoupled the binding of both EBNA-1s to oriP. DNA-cellulose column chromatography identified two protein species which competed for and uncoupled the binding of EBNA-1 to oriP. The two cellular competitors the authors called anti-EBNA-1 proteins had molecular masses of 60 and 40 kilodaltons, respectively. They were not found in nuclear extracts of BJAB cells not activated by 12-O-tetradecanoylphorbol-13-acetate.

  13. Cellularized Bilayer Pullulan-Gelatin Hydrogel for Skin Regeneration.

    Science.gov (United States)

    Nicholas, Mathew N; Jeschke, Marc G; Amini-Nik, Saeid

    2016-05-01

    Skin substitutes significantly reduce the morbidity and mortality of patients with burn injuries and chronic wounds. However, current skin substitutes have disadvantages related to high costs and inadequate skin regeneration due to highly inflammatory wounds. Thus, new skin substitutes are needed. By combining two polymers, pullulan, an inexpensive polysaccharide with antioxidant properties, and gelatin, a derivative of collagen with high water absorbency, we created a novel inexpensive hydrogel-named PG-1 for "pullulan-gelatin first generation hydrogel"-suitable for skin substitutes. After incorporating human fibroblasts and keratinocytes onto PG-1 using centrifugation over 5 days, we created a cellularized bilayer skin substitute. Cellularized PG-1 was compared to acellular PG-1 and no hydrogel (control) in vivo in a mouse excisional skin biopsy model using newly developed dome inserts to house the skin substitutes and prevent mouse skin contraction during wound healing. PG-1 had an average pore size of 61.69 μm with an ideal elastic modulus, swelling behavior, and biodegradability for use as a hydrogel for skin substitutes. Excellent skin cell viability, proliferation, differentiation, and morphology were visualized through live/dead assays, 5-bromo-2'-deoxyuridine proliferation assays, and confocal microscopy. Trichrome and immunohistochemical staining of excisional wounds treated with the cellularized skin substitute revealed thicker newly formed skin with a higher proportion of actively proliferating cells and incorporation of human cells compared to acellular PG-1 or control. Excisional wounds treated with acellular or cellularized hydrogels showed significantly less macrophage infiltration and increased angiogenesis 14 days post skin biopsy compared to control. These results show that PG-1 has ideal mechanical characteristics and allows ideal cellular characteristics. In vivo evidence suggests that cellularized PG-1 promotes skin regeneration and may

  14. Gesture Recognition Based Mouse Events

    Directory of Open Access Journals (Sweden)

    Rachit Puri

    2013-12-01

    Full Text Available This paper presents the maneuver of mouse pointer a nd performs various mouse operations such as left click, right click, double click, drag etc using ge stures recognition technique. Recognizing gestures is a complex task which involves many aspects such as mo tion modeling, motion analysis, pattern recognition and machine learning. Keeping all the essential factors in mind a system has been created which recognizes the movement of fingers and various patterns formed by them. Color caps have been used for fingers to distinguish it f rom the background color such as skin color. Thus recog nizing the gestures various mouse events have been performed. The application has been created on MATL AB environment with operating system as windows 7.

  15. Skin color - patchy

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/003224.htm Skin color - patchy To use the sharing features on this page, please enable JavaScript. Patchy skin color is areas where the skin color is irregular. ...

  16. Application and detection of (14)c-hd in two mouse models.

    Science.gov (United States)

    Logan, Thomas P; Shutz, Michael; Schulz, Susan M; Railer, Roy; Ricketts, Karen M; Casillas, Robert P

    2002-01-01

    The CD1-haired mouse and the SKH-hairless mouse are two animal models that have been used to evaluate sulfur mustard (HD) exposure and protection in our laboratory. In a recent study we observed that a substance P inhibitor protected the haired mouse ear against an HD solution, but the same drug was not successful in protecting the hairless mouse against HD vapor. This experiment prompted us to compare HD exposures between these models. We determined the (14)C content in the skin after exposures to HD containing (14)C-HD. Rate curves were generated for applications of (1) HD in methylene chloride to the haired mouse ear; (2) HD in methylene chloride to the hairless mouse dorsal skin; and (3) saturated HD vapor to the hairless mouse dorsal skin for 6 min. The curves showed a reduction in (14)C disintegrations per min in animals euthanized 0 to 2 h postexposure. The largest percentage of decrease of (14)C content in skin occurred within 30 min of HD challenge for all exposures. An 8-mm skin-punch biopsy and a 14-mm annular skin section surrounding the region of the 8-mm skin punch were taken from the hairless mouse dorsal skin exposed to HD in methylene chloride. The ratio of the (14)C content in the 8-mm skin punch to that in the surrounding 14-mm annular skin section was 7.3, demonstrating that the HD application spreads beyond the initially biopsied site. A concentration/time value of 6.3 mug/cm(2)/min was determined by counting skin (14)C disintegrations per minute in animals euthanized immediately after exposure to saturated HD vapor. Determinations of the amount of HD showed that similar quantities of HD, 0.4 mg, were detected on each model. These results contribute to a better quantitative understanding of HD application in the haired and hairless mouse models.

  17. Periplogenin induces necroptotic cell death through oxidative stress in HaCaT cells and ameliorates skin lesions in the TPA- and IMQ-induced psoriasis-like mouse models.

    Science.gov (United States)

    Zhang, Wen-Jing; Song, Zhen-Bo; Bao, Yong-Li; Li, Wen-Liang; Yang, Xiao-Guang; Wang, Qi; Yu, Chun-Lei; Sun, Lu-Guo; Huang, Yan-Xin; Li, Yu-Xin

    2016-04-01

    Psoriasis is a multifactorial skin disease that inconveniences many patients. Considering the side effects and drug resistance of the current therapy, it is urgent to discover more effective and safer anti-psoriatic drugs. In the present study, we screened over 250 traditional Chinese medicine compounds for their ability to inhibit the cell viability of cultured human HaCaT keratinocytes, a psoriasis-relevant in vitro model, and found that periplogenin was highly effective. Mechanistic studies revealed that apoptosis and autophagy were not induced by periplogenin in HaCaT cells. However, periplogenin caused PI to permeate into cells, increased lactate LDH release and rapidly increased the number of necrotic cells. Additionally, the typical characteristics of necrosis were observed in the periplogenin-treated HaCaT cells. Notably, the necroptosis inhibitor Nec-1 and NSA were able to rescue the cells from necrotic cell death, supporting that necroptosis was involved in periplogenin-induced cell death. Furthermore, the ROS levels were elevated in the periplogenin-treated cells, NAC (an antioxidant) and Nec-1 could inhibit the ROS levels, and NAC could attenuate necroptotic cell death, indicating that the periplogenin-induced necroptotic cell death was mediated by oxidative stress. More importantly, in the murine models of TPA-induced epidermal hyperplasia and IMQ-induced skin inflammation, topical administration of periplogenin ameliorated skin lesions and inflammation. In sum, our results indicate, for the first time, that periplogenin is a naturally occurring compound with potent anti-psoriatic effects in vitro and in vivo, making it a promising candidate for future drug research.

  18. Iron in Skin of Mice with Three Etiologies of Systemic Iron Overload

    OpenAIRE

    2005-01-01

    In human hemochromatosis, tissue toxicity is a function of tissue iron levels. Despite reports of skin toxicity in hemochromatosis, little is known about iron levels in skin of individuals with systemic iron overload. We measured skin iron and studied skin histology in three mouse models of systemic iron overload: mice with a deletion of the hemochromatosis (Hfe) gene, mice fed a high iron diet, and mice given parenteral injections of iron. In Hfe−/− mice, iron content in the epidermis and de...

  19. Skin Care and Aging

    Science.gov (United States)

    ... 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 ...

  20. What Is Melanoma Skin Cancer?

    Science.gov (United States)

    ... Skin Cancer About Melanoma Skin Cancer What Is Melanoma Skin Cancer? Cancer starts when cells in the ... pigment, causing the skin to tan or darken. Melanoma skin cancers Melanoma is a cancer that begins ...

  1. Human papillomaviruses and skin cancer.

    Science.gov (United States)

    Smola, Sigrun

    2014-01-01

    Human papillomaviruses (HPVs) infect squamous epithelia and can induce hyperproliferative lesions. More than 120 different HPV types have been characterized and classified into five different genera. While mucosal high-risk HPVs have a well-established causal role in anogenital carcinogenesis, the biology of cutaneous HPVs is less well understood. The clinical relevance of genus beta-PV infection has clearly been demonstrated in patients suffering from epidermodysplasia verruciformis (EV), a rare inherited disease associated with ahigh rate of skin cancer. In the normal population genus beta-PV are suspected to have an etiologic role in skin carcinogenesis as well but this is still controversially discussed. Their oncogenic potency has been investigated in mouse models and in vitro. In 2009, the International Agency for Research on Cancer (IARC) classified the genus beta HPV types 5 and 8 as "possible carcinogenic" biological agents (group 2B) in EV disease. This chapter will give an overview on the knowns and unknowns of infections with genus beta-PV and discuss their potential impact on skin carcinogenesis in the general population.

  2. 人Stro-1+间充质干细胞诱导小鼠皮肤移植免疫耐受的初步研究%Immune Tolerance Induced by Human Stro-1 Positive Mesenchymal Stem Cells in Mouse Skin Graft

    Institute of Scientific and Technical Information of China (English)

    李芳; 许雯; 李晓武; 张翼鷟

    2012-01-01

    本研究探讨人间充质干细胞(MSC)及其Stro-1 +MSC亚群对小鼠皮肤移植模型的诱导移植免疫耐受作用.从健康成人骨髓单个核细胞中培养MSC,并筛选Stro-1+ MSC.建立小鼠同种异体皮肤移植模型,供体为雌性C57BL/6小鼠,获取皮片,移植给受体雌性BALB/c小鼠.动物分为4组:①Stro-1+ MSC组:照射受鼠移植前输注2×106 Stro-1+ MSC;②MSC组:照射受鼠移植前输注2 ×106 MSC;③照射对照组:受鼠照射后直接进行皮肤移植;④同系对照组:BALB/c小鼠照射后接受同系小鼠皮肤移植.检测项目包括:移植皮片存活时间,HE染色观察移植皮片病理改变,ELISA检测移植前后受鼠血浆转化生长因子β1( TGF-β1)浓度的变化.结果显示:MSC组皮肤移植物存活时间为(12.13±3.34)d,较照射对照组(11.38±1.01)d未见明显延长(P>0.05);Stro-1+ MSC组皮肤移植物存活时间为(30.68±5.89)d,较照射对照组及MSC组明显延长(P<0.05),移植皮肤病理检查显示皮片结构清晰.在同系对照组和照射对照组,移植前后受鼠血浆中TGF-β1浓度无显著变化,而在MSC组和Stro-1+MSC组移植后TGF-β1浓度均有显著增高(P<0.05).结论:Stro-1+ MSC较未分选的MSC具有更强的诱导移植免疫耐受的功能,在体内可显著延长小鼠皮片的存活时间,而这种作用似与TGF-β1的表达无关.%This study was aimed to evaluate whether human mesenchymal stem cell( MSC) and the Stro-1 positive subgroup have inducing immune tolerance effect in mouse skin graft model. Human MSC were isolated and cultured from bone marrow-derived mononuclear cells of healthy adults, and Stro-1 positive cells were sorted out. Female C57BL/6 mice and female BALB/c mice were respectively used as donors and recipients in skin allogenic graft model. The recipients were divided randomly into 4 groups; (1) Stro-1 + MSC group; 2 x 10' Stro-1f MSC were injected into the irradiated recipient mice before skin graft. (2) MSC group: 2

  3. Liquid Crystal Gel Reduces Age Spots by Promoting Skin Turnover

    OpenAIRE

    Mina Musashi; Ariella Coler-Reilly; Teruaki Nagasawa; Yoshiki Kubota; Satomi Kato; Yoko Yamaguchi

    2014-01-01

    Studies have shown that liquid crystals structurally resembling the intercellular lipids in the stratum corneum can beneficially affect the skin when applied topically by stimulating the skin’s natural regenerative functions and accelerating epidermal turnover. In the present study, the effects of applying low concentrations of a liquid crystal gel of our own creation were evaluated using epidermal thickening in mouse skin as an assay for effective stimulation of epidermal turnover. A liquid ...

  4. Time-dependent Recruitment and Differentiation of Fibrocytes in Mouse Skin Wound Healing%小鼠皮肤切创愈合过程中纤维细胞募集和分化的时间依赖性

    Institute of Scientific and Technical Information of China (English)

    范琰琰; 官大威; 王涛; 刘伟伟; 郑吉龙; 赵振宾; 于天水; 马文翔

    2011-01-01

    目的 观察小鼠皮肤切创愈合过程中,纤维细胞募集和分化随时间变化的规律性.方法 应用免疫荧光技术共定位纤维细胞[共表达CD45、Ⅰ型前胶原(procollagen Ⅰ)]和肌成纤维细胞[共表达CD45、平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)],计数纤维细胞及其分化成的肌成纤维细胞.结果 纤维细胞于切创后3d募集于创口局部,其分化成的肌成纤维细胞于切创后5d开始出现于肉芽区.纤维细胞及其分化成的肌成纤维细胞于伤后7d达到峰值.结论 在小鼠皮肤切创愈合过程中,肉芽组织中的肌成纤维细胞至少部分来源于纤维细胞的分化,纤维细胞时间依赖性地募集和分化可以为损伤时间的推断提供新的信息.%Objective To investigate the time-dependent recruitment and differentiation of fibrocytes in skin wound healing. Methods Fibrocytes (expressing CD45 and procollagen I ) and myofibroblasts (expressing CD45 and α-SMA) were co-localized by immunofluorescent staining. The number of fibrocytes and myofibroblasts was counted at different post-wounding interval. Results At 3d after injury, fibrocytes started to recruit at the margin of the wounds. At 5 d after injury, myofibroblasts started to appear in new formed granulation tissue. The number of fibrocytes and myofibroblasts peaked at 7 d post-wounding. Conclusion During skin wound healing, myofibroblasts in granulation tissue originated at least partly from fibrocytie differentiation. The time-dependent recruitment and differentiation of fibrocytes may provide new information for wound age determination.

  5. [Sarcoidosis of the skin].

    Science.gov (United States)

    Suga, Y; Ogawa, H

    1994-06-01

    Sarcoidosis is characterized by formation of epithelioid-cell tubercules, without caseation, of the affected organ systems. The mediastinum, peripheral lymph nodes and eyes, in addition to the skin, are most frequently affected. Between 10% and 30% of patients with systemic sarcoidosis in Japan have skin lesions. Skin sarcoidosis is morphologically classified into three basic groups, erythema nodosum, scar sarcoidosis and skin sarcoid. Skin sarcoid is characterized by specific cutaneous lesions of sarcoidosis, and may take nodular, plaque, angiolupoid, subcutaneous and some other forms. Clinical manifestations of the cutaneous lesions are usually asymptomatic and polymorphous. Skin biopsy is, however, often highly useful for confirming a diagnosis of sarcoidosis.

  6. Skin Stem Cells in Skin Cell Therapy

    Directory of Open Access Journals (Sweden)

    Mollapour Sisakht

    2015-12-01

    Full Text Available Context Preclinical and clinical research has shown that stem cell therapy is a promising therapeutic option for many diseases. This article describes skin stem cells sources and their therapeutic applications. Evidence Acquisition Compared with conventional methods, cell therapy reduces the surgical burden for patients because it is simple and less time-consuming. Skin cell therapy has been developed for variety of diseases. By isolation of the skin stem cell from the niche, in vitro expansion and transplantation of cells offers a surprising healing capacity profile. Results Stem cells located in skin cells have shown interesting properties such as plasticity, transdifferentiation, and specificity. Mesenchymal cells of the dermis, hypodermis, and other sources are currently being investigated to promote regeneration. Conclusions Because skin stem cells are highly accessible from autologous sources and their immunological profile is unique, they are ideal for therapeutic approaches. Optimization of administrative routes requires more investigation own to the lack of a standard protocol.

  7. Radionecrosis skin model induced an athymic mouse nude (Nu/Nu) for development of dermal-epidermal human substitute based regenerative therapy; Modelo de radionecrose cutanea induzida em camundongos Nude (Nu/Nu) para desenvolvimento de terapias regenerativas baseadas em substitutos dermo-epidermicos humanos

    Energy Technology Data Exchange (ETDEWEB)

    Mosca, Rodrigo Crespo

    2014-07-01

    The neoplasms incidence has increased significantly in recent years and continued population growth and aging will increase the statistics of this illness in the world's diseases. The cancer treatment usually consists in individual or combined use of chemotherapy, surgery and radiotherapy depending on the etiology of the tumor. In cases where radiotherapy is used in addition to the therapeutic effects of radiation, specific complications can occur, and in the skin, these complications can be present with a clinical expression ranging from erythema to radionecrosis, and this latter being the adverse effect with greater severity. The radionecrosis treatment consists in debridement necrotic areas and covering the surgical wounds. Autologous grafts are most commonly used for this covering, however when large areas are affected, allografts can be used for occlusive treatment and the keratinocytes and adipose derived stem cells (ADSC) addition becomes an alternative, due to the knowing for immunomodulatory and regenerative response. For that reason, aiming to simulate the radionecrosis adverse effects, an animal model of induced cutaneous radionecrosis was created, in athymic mouse Nude (Nu/Nu), for developing regenerative therapies based on human dermal-epidermal substitutes containing keratinocytes and ADSC, which proved occlusive as an efficient treatment, furthermore, having this radionecrosis animal model established, new possibilities for treatment of diseases involving dermal regeneration, can be tested. (author)

  8. Examine Your Skin

    Medline Plus

    Full Text Available ... 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 ...

  9. Examine Your Skin

    Medline Plus

    Full Text Available ... Support Donate Share Facebook Twitter Newsletter Examine Your Skin Watch the video below and in only two minutes, you can learn to examine your skin. A special thanks to Dr. Martin Weinstock, MD, ...

  10. Neuromodulators for Aging Skin

    Science.gov (United States)

    ... Dermatologic Surgery Expertise for the life of your skin (TM) Public Resources Dermatologic Surgery Conditions Treatments and ... learn-more"> 3 million Americans are diagnosed with skin cancer every year Any suspicious new growths or ...

  11. 含鼠胚胎成纤维细胞的组织工程皮肤体外构建及大鼠移植研究%Construction and transplantation of tissue-engineered skin with mouse embryonic fibroblasts in SD mice

    Institute of Scientific and Technical Information of China (English)

    刘柳; 李武德; 蔡国斌

    2011-01-01

    Objective To investigate the application and mechanism of tissue-engineered skin with mouse embryonic fibroblasts(MEFs)for the full-thickness skin defects on mice.Methods The MEFs and fibroblasts were cultured and seeded in scaffold made of rat tail collage.ELISA method was used for detection of secretory function.The full-thickness skin defects were created on mice and covered by MEFsscaffold complex(experimental group),or FBs-scaffold complex(control group 1),or scaffold only(control group 2).The process of wound healing was evaluated by observation of the re-epithelization rate.Microvessal density(MVD)and vimentin within the wound sites were also detected with immunohistochemistry staining technique to describe the characteristics of wound healing.Hoechst 33342 staining was performed to trace MEFs'fate.Results MEFs scaffold group had higher level secretion of IL-6 and lower of TGF-β1 than FBs scaffold group(P<0.05).Compared with wounds in control groups,the wounds in MEFs group healed markedly fast(P<0.05)and the MVD was significantly higher(P<0.05).The fibroblasts in the wounds of MEFs group were arranged regularly and the MEFs decreased during the healing process.Conclusions The MEFs-scaffold complex can promote wound healing with less scar formation.MEFs may have an inducing effect on the wound healing.%目的 利用鼠胚胎成纤维细胞(mouse embryonic fibrobalsts,MEFs)三维培养修复大鼠全层皮肤缺损,并初步探讨其机制.方法 培养MEFs和普通成纤维细胞(fibroblasts,FBs),复合鼠尾胶原形成三维构建,ELASA法测定其分泌功能.制作大鼠全层皮肤缺损,按移植物不同分为3组:MEFs组(实验组)、FBs组(对照组1)和空白胶原组(对照组2).观察愈合时间并计算愈合面积比率,定期取创面组织行CD31、波形蛋白免疫组化检测,并以Hoechst33342荧光标记MEFs,示踪其转归.结果 与FBs组相比,MEFs组的IL-6分泌更加旺盛,而TGF-β1分泌量少(P<0.05).

  12. Skin Cancer Trends

    Science.gov (United States)

    ... Trends Behavior Rates What CDC Is Doing Skin Cancer Prevention Progress Report The Burning Truth Initiative A Base Tan Is Not a Safe Tan Tanned Skin Is Not Healthy Skin Controlled Tanning Is Not Safe Tanning Guidelines for School ... Melanoma Surveillance in the U.S. Related Links ...

  13. On skin expansion.

    Science.gov (United States)

    Pamplona, Djenane C; Velloso, Raquel Q; Radwanski, Henrique N

    2014-01-01

    This article discusses skin expansion without considering cellular growth of the skin. An in vivo analysis was carried out that involved expansion at three different sites on one patient, allowing for the observation of the relaxation process. Those measurements were used to characterize the human skin of the thorax during the surgical process of skin expansion. A comparison between the in vivo results and the numerical finite elements model of the expansion was used to identify the material elastic parameters of the skin of the thorax of that patient. Delfino's constitutive equation was chosen to model the in vivo results. The skin is considered to be an isotropic, homogeneous, hyperelastic, and incompressible membrane. When the skin is extended, such as with expanders, the collagen fibers are also extended and cause stiffening in the skin, which results in increasing resistance to expansion or further stretching. We observed this phenomenon as an increase in the parameters as subsequent expansions continued. The number and shape of the skin expanders used in expansions were also studied, both mathematically and experimentally. The choice of the site where the expansion should be performed is discussed to enlighten problems that can lead to frustrated skin expansions. These results are very encouraging and provide insight into our understanding of the behavior of stretched skin by expansion. To our knowledge, this study has provided results that considerably improve our understanding of the behavior of human skin under expansion.

  14. Skin self-exam

    Science.gov (United States)

    Skin cancer - self-exam; Melanoma - self-exam; Basal cell cancer - self-exam; Squamous cell - self-exam; Skin mole - self-exam ... Experts do not agree on whether or not skin self-exams should be performed. So there is ...

  15. Microbiome and skin diseases

    NARCIS (Netherlands)

    Zeeuwen, P.L.J.M.; Kleerebezem, M.; Timmerman, H.M.; Schalkwijk, J.

    2013-01-01

    PURPOSE OF REVIEW: This article reviews recent findings on the skin microbiome. It provides an update on the current understanding of the role of microbiota in healthy skin and in inflammatory and allergic skin diseases. RECENT FINDINGS: Advances in computing and high-throughput sequencing technolog

  16. Microbiome and skin diseases

    NARCIS (Netherlands)

    Zeeuwen, P.L.; Kleerebezem, M.; Timmerman, H.M.; Schalkwijk, J.

    2013-01-01

    Purpose of review: This article reviews recent findings on the skin microbiome. It provides an update on the current understanding of the role of microbiota in healthy skin and in inflammatory and allergic skin diseases. Recent findings: Advances in computing and high-throughput sequencing technolog

  17. Ultrasound skin imaging.

    Science.gov (United States)

    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.

  18. Psychoneuroimmunology and the Skin.

    Science.gov (United States)

    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.

  19. The preventive effect of linalool on acute and chronic UVB-mediated skin carcinogenesis in Swiss albino mice.

    Science.gov (United States)

    Gunaseelan, Srithar; Balupillai, Agilan; Govindasamy, Kanimozhi; Muthusamy, Ganesan; Ramasamy, Karthikeyan; Shanmugam, Mohana; Prasad, N Rajendra

    2016-07-01

    In this study, we evaluated the role of linalool in acute ultraviolet-B (UVB; 280-320 nm) radiation-induced inflammation and chronic UVB-mediated photocarcinogenesis in mouse skin. Acute UVB-irradiation (180 mJ cm(-2)) causes hyperplasia, edema formation, lipid peroxidation, antioxidant depletion, and overexpression of cyclooxygenase-2 (COX-2) and ornithine decarboxylase (ODC) in mouse skin. Topical or intraperitoneal (i.p.) treatment of linalool prevented acute UVB-induced hyperplasia, edema formation, lipid peroxidation, and antioxidant depletion in mouse skin. Further, linalool treatment prevented UVB-induced overexpression of COX-2 and ODC in mouse skin. In the chronic study, mice were subjected to UVB-exposure thrice weekly for 30 weeks. Chronic UVB-exposure induced tumor incidence and expression of proliferative markers such as NF-κB, TNF-α, IL-6, COX-2, VEGF, TGF-β1, Bcl-2 and mutated p53 in mouse skin. Treatment with linalool before each UVB-exposure significantly prevented the expression of these proliferative markers and subsequently decreased the tumor incidence in mice skin. Histopathological studies confirmed the development of dysplasia and squamous cell carcinoma (SCC) in the chronic UVB-exposed mouse skin; and this was prevented by both topical and i.p. linalool treatment. Therefore, linalool may be considered as a photochemopreventive agent against UVB radiation induced skin carcinogenesis.

  20. Identification of a novel skin penetration enhancement peptide by phage display peptide library screening.

    Science.gov (United States)

    Kumar, Sunny; Sahdev, Preety; Perumal, Omathanu; Tummala, Hemachand

    2012-05-07

    Skin is an important site for local or systemic application of drugs. However, a majority of drugs have poor permeability through the skin's topmost layer, stratum corneum (SC). The aim of this study was to identify safe and smaller peptides that could enhance the skin penetration of drug molecules. By screening phage display peptide library, we have identified a T2 peptide (LVGVFH), which enhanced the penetration of bacteriophages (~800 nm long bacterial viruses) across porcine and mouse skin. Pretreating the skin with synthetic T2 peptide at pH 4.5 resulted in significant penetration enhancement of hydrophilic drug 5-fluorouracil (5-FU) across skin. FTIR spectroscopy showed that the T2 peptide interacted with skin lipids to enhance the skin penetration. Pretreating the skin with T2 peptide enhanced the partitioning of small molecules with different lipophilicities (5-FU, fluorescein isothiocyanate, and rhodamine 123 hydrochloride) into skin. Fluorescence studies showed that T2 peptide enhanced the diffusion of these molecules into intercellular lipids of SC and thus enhanced the penetration into the skin. Histidine at the c-terminus of T2 peptide was identified to be critical for the skin penetration enhancement. T2 peptide interacted with skin lipids to cause skin penetration enhancement. The study identified a novel, safe, and noninvasive peptide to improve the skin penetration of drugs without chemical conjugation.

  1. Pursuing prosthetic electronic skin

    Science.gov (United States)

    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.

  2. Local inflammation exacerbates the severity of Staphylococcus aureus skin infection.

    Directory of Open Access Journals (Sweden)

    Christopher P Montgomery

    Full Text Available Staphylococcus aureus is the leading cause of skin infections. In a mouse model of S. aureus skin infection, we found that lesion size did not correlate with bacterial burden. Athymic nude mice had smaller skin lesions that contained lower levels of myeloperoxidase, IL-17A, and CXCL1, compared with wild type mice, although there was no difference in bacterial burden. T cell deficiency did not explain the difference in lesion size, because TCR βδ (-/- mice did not have smaller lesions, and adoptive transfer of congenic T cells into athymic nude mice prior to infection did not alter lesion size. The differences observed were specific to the skin, because mortality in a pneumonia model was not different between wild type and athymic nude mice. Thus, the clinical severity of S. aureus skin infection is driven by the inflammatory response to the bacteria, rather than bacterial burden, in a T cell independent manner.

  3. Skin absorption through atopic dermatitis skin

    DEFF Research Database (Denmark)

    Halling-Overgaard, A-S; Kezic, S; Jakasa, I

    2017-01-01

    Patients with atopic dermatitis have skin barrier impairment in both lesional and non-lesional skin. They are typically exposed to emollients daily and topical anti-inflammatory medicaments intermittently, hereby increasing the risk of developing contact allergy and systemic exposed to chemicals...... ingredients found in these topical preparations. We systematically searched for studies that investigated skin absorption of various penetrants, including medicaments, in atopic dermatitis patients, but also animals with experimentally induced dermatitis. We identified 40 articles, i.e. 11 human studies...... examining model penetrants, 26 human studies examining atopic dermatitis drugs and 3 animal studies. We conclude that atopic dermatitis patients have nearly two-fold increased skin absorption when compared to healthy controls. There is a need for well-designed epidemiological and dermato...

  4. COMPARATIVE GENOTOXIC RESPONSES TO ARSENITE IN GUINEA PIG, MOUSE, RAT AND HUMAN LYMPHOCYTES

    Science.gov (United States)

    Comparative genotoxic responses to arsenite in guinea pig, mouse, rat and human lymphocytes.Inorganic arsenic is a known human carcinogen causing skin, lung, and bladder cancer following chronic exposures. Yet, long-term laboratory animal carcinogenicity studies have ...

  5. Skin barrier function

    DEFF Research Database (Denmark)

    2016-01-01

    Renowned experts present the latest knowledge Although a very fragile structure, the skin barrier is probably one of the most important organs of the body. Inward/out it is responsible for body integrity and outward/in for keeping microbes, chemicals, and allergens from penetrating the skin. Since...... the role of barrier integrity in atopic dermatitis and the relationship to filaggrin mutations was discovered a decade ago, research focus has been on the skin barrier, and numerous new publications have become available. This book is an interdisciplinary update offering a wide range of information...... on the subject. It covers new basic research on skin markers, including results on filaggrin and on methods for the assessment of the barrier function. Biological variation and aspects of skin barrier function restoration are discussed as well. Further sections are dedicated to clinical implications of skin...

  6. Expression levels of 3 cytokines in judging the injury time in the healing process of mouse skin wounds%小鼠皮肤创伤修复中3种细胞因子表达水平对损伤时间的评估

    Institute of Scientific and Technical Information of China (English)

    王慧君; 李学锋; 刘明

    2005-01-01

    BACKGROUND: Wound healing is a complex biological process regulated temporally and spatially by many repair factors. Studies have showed the predominant expression of cytokines in wound healing process, which is a kind of molecular vital reaction, and may be a new reference index in wound age estimation. But the precise relation of the expressions of cytokines and distribution to wound age is not clear.OBJECTIVE: To probe into the relation of the expressions of cytokines and distribution to wound age in the healing process of the mouse skin wounds.DESIGN: A randomized controlled confirmation study based on the experimental animalsSETTING: Department of Pathology of the First Military University of Chinese PLA, which is a key laboratory of molecule oncology of Chinese PLA.MATERIALS: The study was completed in the Key Laboratory of Molecule Oncdogy of Chinese PLA from July to September in 2003. Sixty-five Kunming mice of either gender, weighing 25 - 28 g, were involved.INTERVENTIONS: The mice were randomly divided into the experimental and the control group. The mice in the experimental group were divided into 12 subgroups according to the different times of trauma. The mice were killed at the following time intervals: 15 minutes, 30 minutes, 1 hour, 3 hours, 6hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week or 2 weeks after wound and the wounded skin was excised( n = 5 each). As a control, 5mice without wounding were examined.MAIN OUTCOME MEASURES: The amount and distribution of staining positive inflammation and repair cells in skin wound tissues.RESULTS: Persistent positive expression of vascular endothelial growth factor(VEGF) was seen in the epidermal cells and sebaceous gland cells. The expressions of transforming growth factor β1(TGF-β1) and basic fibroblast growth factor (bFGF) in the epidermal cells were increased at 3 hours after incision and lasted till 12 hours and 48 hours respectively. There was a similar distribution in the positive

  7. Skin Images Segmentation

    Directory of Open Access Journals (Sweden)

    Ali E. Zaart

    2010-01-01

    Full Text Available Problem statement: Image segmentation is a fundamental step in many applications of image processing. Skin cancer has been the most common of all new cancers detected each year. At early stage detection of skin cancer, simple and economic treatment can cure it mostly. An accurate segmentation of skin images can help the diagnosis to define well the region of the cancer. The principal approach of segmentation is based on thresholding (classification that is lied to the problem of the thresholds estimation. Approach: The objective of this study is to develop a method to segment the skin images based on a mixture of Beta distributions. We assume that the data in skin images can be modeled by a mixture of Beta distributions. We used an unsupervised learning technique with Beta distribution to estimate the statistical parameters of the data in skin image and then estimate the thresholds for segmentation. Results: The proposed method of skin images segmentation was implemented and tested on different skin images. We obtained very good results in comparing with the same techniques with Gamma distribution. Conclusion: The experiment showed that the proposed method obtained very good results but it requires more testing on different types of skin images.

  8. Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation.

    Science.gov (United States)

    Li, Wenjuan; Zhang, Chunjing; Ren, Amy; Li, Teena; Jin, Rong; Li, Guohong; Gu, Xin; Shi, Runhua; Zhao, Yunfeng

    2015-01-01

    The M2 isoform of pyruvate kinase M2 (PKM2) has been shown to be up-regulated in human skin cancers. To test whether PKM2 may be a target for chemoprevention, shikonin, a natural product from the root of Lithospermum erythrorhizon and a specific inhibitor of PKM2, was used in a chemically-induced mouse skin carcinogenesis study. The results revealed that shikonin treatment suppressed skin tumor formation. Morphological examinations and immunohistochemical staining of the skin epidermal tissues suggested that shikonin inhibited cell proliferation without inducing apoptosis. Although shikonin alone suppressed PKM2 activity, it did not suppress tumor promoter-induced PKM2 activation in the skin epidermal tissues at the end of the skin carcinogenesis study. To reveal the potential chemopreventive mechanism of shikonin, an antibody microarray analysis was performed, and the results showed that the transcription factor ATF2 and its downstream target Cdk4 were up-regulated by chemical carcinogen treatment; whereas these up-regulations were suppressed by shikonin. In a promotable skin cell model, the nuclear levels of ATF2 were increased during tumor promotion, whereas this increase was inhibited by shikonin. Furthermore, knockdown of ATF2 decreased the expression levels of Cdk4 and Fra-1 (a key subunit of the activator protein 1. In summary, these results suggest that shikonin, rather than inhibiting PKM2 in vivo, suppresses the ATF2 pathway in skin carcinogenesis.

  9. Skin tribology: Science friction?

    NARCIS (Netherlands)

    Heide, van der E.; Zeng, X.; Masen, M.A.

    2013-01-01

    The application of tribological knowledge is not just restricted to optimizing mechanical and chemical engineering problems. In fact, effective solutions to friction and wear related questions can be found in our everyday life. An important part is related to skin tribology, as the human skin is fre

  10. Deformable skinning on bones

    DEFF Research Database (Denmark)

    Larsen, Bent Dalgaard; Petersen, Kim Steen; Jakobsen, Bjarke

    2001-01-01

    Applying skin to a model is a relatively simple task to implement. Nonetheless it seems that no good resource exists that describes both the concepts and math necessary to understand and implement skinning. The intention of this article is an attempt to give a thoroughly description of the theore...

  11. Skin Diseases: Skin and Sun—Not a good mix

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Skin and Sun —Not a good mix Past Issues / ... of this page please turn Javascript on. Good skin care begins with sun safety. Whether it is ...

  12. Bionanomaterials for skin regeneration

    CERN Document Server

    Leonida, Mihaela D

    2016-01-01

    This book gives a concise overview of bionanomaterials with applications for skin regeneration. The advantages and challenges of nanoscale materials are covered in detail, giving a basic view of the skin structure and conditions that require transdermal or topical applications. Medical applications, such as wound healing, care for burns, skin disease, and cosmetic care, such as aging of the skin and photodamage, and how they benefit from bionanomaterials, are described in detail. A final chapter is devoted to the ethical and social issues related to the use of bionanomaterials for skin regeneration. This is an ideal book for researchers in materials science, medical scientists specialized in dermatology, and cosmetic chemists working in formulations. It can also serve as a reference for nanotechnologists, dermatologists, microbiologists, engineers, and polymer chemists, as well as students studying in these fields.

  13. N-Nicotinoyl dopamine, a novel niacinamide derivative, retains high antioxidant activity and inhibits skin pigmentation.

    Science.gov (United States)

    Kim, Bora; Kim, Jin Eun; Lee, Su Min; Lee, Soung-Hoon; Lee, Jin Won; Kim, Myung Kyoo; Lee, Kye Jong; Kim, Hyuk; Lee, Joo Dong; Choi, Kang-Yell

    2011-11-01

    We synthesized a novel derivative of a well-known skin-lightening compound niacinamide, N-nicotinoyl dopamine (NND). NND did not show inhibitory effects of tyrosinase and melanin synthesis in B16F10 mouse melanoma cells. However, NND retains high antioxidant activity without affecting viability of cells. In a reconstructed skin model, topical applications of 0.05% and 0.1% NND induced skin lightening and decreased melanin production without affecting the viability and morphology of melanocytes and overall tissue histology. Moreover, no evidence for skin irritation or sensitization was observed when 0.1% NND emulsion was applied onto the skin of 52 volunteers. The effect of NND on skin lightening was further revealed by pigmented spot analyses of human clinical trial. Overall, NND treatment may be a useful trial for skin lightening and treating pigmentary disorders.

  14. Surface proteins of Staphylococcus aureus play an important role in experimental skin infection.

    Science.gov (United States)

    Kwiecinski, Jakub; Jin, Tao; Josefsson, Elisabet

    2014-12-01

    Staphylococcus aureus is the most common cause of skin infections that range from mild diseases up to life-threatening conditions. Mechanisms of S. aureus virulence in those infections remain poorly studied. To investigate the impact of S. aureus surface proteins on skin infection, we used mouse models of skin abscess formation and skin necrosis, induced by a subcutaneous injection of bacteria. In the skin abscess model, a sortase-deficient S. aureus strain lacking all of its cell-wall anchored proteins was less virulent than its wild-type strain. Also, strains specifically lacking protein A, fibronecting binding proteins, clumping factor A or surface protein SasF were impaired in their virulence. When a model of dermonecrosis was studied, the S. aureus surface proteins could not be shown to be involved. In summary, surface proteins play an important role in virulence of S. aureus skin abscess infections, but not in formation of skin necrosis.

  15. Tips for Relieving Dry Skin

    Science.gov (United States)

    ... skin is dry, stop using: Deodorant soaps Skin care products that contain alcohol, fragrance, retinoids, or alpha-hydroxy acid (AHA) Avoiding these products will help your skin retain its natural oils. 6. Wear gloves. Our hands are often ...

  16. 6 Common Cancers - Skin Cancer

    Science.gov (United States)

    ... 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 ...

  17. Skin Picking Disorder

    Directory of Open Access Journals (Sweden)

    Pinar Cetinay Aydin

    2014-08-01

    Full Text Available Skin picking disorder is not a dermatological disorder and it is a table characterized with picking skin excessively and repetitively, leading to damage in skin tissue. Unlike normal picking behaviour, psychogenic skin picking is repetitive and it can lead to severe damage in the skin and even complications which constitute vital danger. While some patients define frequent but short lasting picking attacks, others define rarer attacks which last a few hours. Skin picking disorder, which is not included in the classification systems up to DSM-5 as a separate diagnosis category, is included as an independent diagnosis in Obsessive Compulsive Disorder and Associated Disorders category in DSM-5. In case reports, open label studies and double blind studies selective serotonin reuptake inhibitors are shown to be effective in the treatment of skin picking disorder. Mostly, cognitive-behaviourial techniques are used and have been proven to be useful in psychotherapy. Habit reversal is one of the behaviourial techniques which are frequently applied, give positive results in which well-being state can be maintained. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(4.000: 401-428

  18. Archaea on human skin.

    Directory of Open Access Journals (Sweden)

    Alexander J Probst

    Full Text Available 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.

  19. Skin and antioxidants.

    Science.gov (United States)

    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. Enhancement of hidden structures of early skin fibrosis using polarization degree patterns and Pearson correlation analysis.

    Science.gov (United States)

    Sviridov, Alexander P; Chernomordik, Victor; Hassan, Moinuddin; Boccara, Albert C; Russo, Angelo; Smith, Paul; Gandjbakhche, Amir

    2005-01-01

    The skin of athymic nude mice is irradiated with a single dose of x-ray irradiation that initiated fibrosis. Digital photographs of the irradiated mice are taken by illuminating the mouse skin with linearly polarized probe light of 650 nm. The specific pattern of the surface distribution of the degree of polarization enables the detection of initial skin fibrosis structures that were not visually apparent. Data processing of the raw spatial distributions of the degree of polarization based on Fourier filtering of the high-frequency noise improves subjective perception of the revealed structure in the images. In addition, Pearson correlation analysis provides information about skin structural size and directionality.

  1. Quantitative analysis on collagen morphology in aging skin based on multiphoton microscopy

    Science.gov (United States)

    Wu, Shulian; Li, Hui; Yang, Hongqin; Zhang, Xiaoman; Li, Zhifang; Xu, Shufei

    2011-04-01

    Multiphoton microscopy was employed for monitoring the structure changes of mouse dermis collagen in the intrinsic- or the extrinsic-age-related processes in vivo. The characteristics of textures in different aging skins were uncovered by fast Fourier transform in which the orientation index and bundle packing of collagen were quantitatively analyzed. Some significant differences in collagen-related changes are found in different aging skins, which can be good indicators for the statuses of aging skins. The results are valuable to the study of aging skin and also of interest to biomedical photonics.

  2. Leishmania Skin Test

    Science.gov (United States)

    2010-03-01

    2009, a dose of 50µg will be used in the design of a phase III clinical trial. 15. SUBJECT TERMS LtSTA = Leishmania tropica Skin Test Antigen 16...2010 on a Leishmania Skin Test (LtSTA) developed from the promastigotes of Leishmania tropica . During this period a phase IIB study was in progress...diluent. The final product is referred to as Leishmania tropica Skin Test Antigen (LtSTA). Figure 3 is a schematic diagram of the Drug Product

  3. Ultrasound skin tightening.

    Science.gov (United States)

    Minkis, Kira; Alam, Murad

    2014-01-01

    Ultrasound skin tightening is a noninvasive, nonablative method that allows for energy deposition into the deep dermal and subcutaneous tissue while avoiding epidermal heating. Ultrasound coagulation is confined to arrays of 1-mm(3) zones that include the superficial musculoaponeurotic system and connective tissue. This technology gained approval from the Food and Drug Administration as the first energy-based skin "lifting" device, specifically for lifting lax tissue on the neck, submentum, and eyebrows. Ultrasound has the unique advantage of direct visualization of treated structures during treatment. Ultrasound is a safe and efficacious treatment for mild skin tightening and lifting.

  4. Eicosanoids in skin inflammation.

    Science.gov (United States)

    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.

  5. 静脉用丙种球蛋白对HLA预致敏小鼠异基因皮肤移植的影响%Effects of IVIG on allogenic skin graft in an HLA-A2 pre-sensitized mouse model

    Institute of Scientific and Technical Information of China (English)

    何瑶; 陈瑜君; 黄文生; 熊理守; 陈白莉

    2010-01-01

    目的:探讨IVIG对存在HLA预致敏的异基因皮肤移植的作用及其可能机制。方法自人HLA-A2.1转基因小鼠(C57BL/6-TgN[HLA-2.1])脾脏获取人HLA-A2抗原,分别于第0天、第3及第4周以腹腔注射人HLA-A2抗原的方式对野生型小鼠(C57BL/6)进行预致敏。第7周时连续5天分别以人IVIG、人血清白蛋白、甘氨酸及磷酸盐缓冲液( PBS)给予上述HLA-A2预致敏小鼠腹腔注射进行脱敏处理。第10周时以转HLA-A2.1基因小鼠为供体,野生型小鼠为受体行皮肤移植建立异基因皮肤移植的小鼠模型,以研究人IVIG对人HLA.A2抗原预致敏的小鼠异基因皮肤移植的影响。结果受体小鼠血清中HLA-A2 IgG变化:HLA-A2致敏后小鼠血清中HLA-A2 IgG水平较基线水平显著升高。腹腔注射人IVIG脱敏后,于第9周时可见小鼠血清中HLA-A2 IgG显著降低( P<0.01),与人血清白蛋白、甘氨酸及PBS注射组相比差异有统计学意义( P <0.01)。异基因皮肤移植后各种受体小鼠血清中HLA-A2 IgG水平迅速升高致极高水平( P <0.01),并持续于高水平。小鼠异基因皮肤移植情况:受体小鼠移植皮肤存活时间均约为术后7d,各组间差异无统计学意义( P>0.05)。结论单独使用IVIG对HLA-A2预致敏小鼠进行脱敏处理不能防止皮肤移植术后抗I类HLA抗体的产生,亦不能有效延长移植皮肤存活时间,提示移植后仍需联用其它有效免疫抑制剂以防止术后排斥反应的发生。%Objective To investigate the effect of IVIG on pre-existing anti-HLA-A2 Ab levels and graft skin survival.Methods C57BL/6 wild type mice were sensitized to HLA-A2 by intraperitoneal injec-tion (IP) of HLA-A2 TgN mouse spleen cells (C57BL/6-TgN [HLA-2.1]1Enge SC) expressing human HLA-A2 at day 0, week 3 and 4.Sensitized mice were respectively treated with human IVIG , albumin, gly-cine, or PBS for 5 days during week 7.Skin transplantation

  6. Animal models of skin disease for drug discovery

    Science.gov (United States)

    Avci, Pinar; Sadasivam, Magesh; Gupta, Asheesh; De Melo, Wanessa CMA; Huang, Ying-Ying; Yin, Rui; Rakkiyappan, Chandran; Kumar, Raj; Otufowora, Ayodeji; Nyame, Theodore; Hamblin, Michael R

    2013-01-01

    Introduction Discovery of novel drugs, treatments, and testing of consumer products in the field of dermatology is a multi-billion dollar business. Due to the distressing nature of many dermatological diseases, and the enormous consumer demand for products to reverse the effects of skin photodamage, aging, and hair loss, this is a very active field. Areas covered In this paper, we will cover the use of animal models that have been reported to recapitulate to a greater or lesser extent the features of human dermatological disease. There has been a remarkable increase in the number and variety of transgenic mouse models in recent years, and the basic strategy for constructing them is outlined. Expert opinion Inflammatory and autoimmune skin diseases are all represented by a range of mouse models both transgenic and normal. Skin cancer is mainly studied in mice and fish. Wound healing is studied in a wider range of animal species, and skin infections such as acne and leprosy also have been studied in animal models. Moving to the more consumer-oriented area of dermatology, there are models for studying the harmful effect of sunlight on the skin, and testing of sunscreens, and several different animal models of hair loss or alopecia. PMID:23293893

  7. Beyond the scalpel: targeting hedgehog in skin cancer prevention.

    Science.gov (United States)

    Rudin, Charles M

    2010-01-01

    This perspective places the article by Tang et al. in this issue of the journal (beginning on page 25) in the context of recent work defining the hedgehog signaling pathway as a central etiologic factor and as a therapeutic target in basal cell cancer. Tang et al. show that inhibition of cyclooxygenase activity, either genetically (in a relevant mouse model) or pharmacologically (in the mouse and in patients highly predisposed to develop basal cell skin cancers), may suppress basal cell carcinogenesis. This new study of cyclooxygenase inhibition, together with recent data on the efficacy of hedgehog pathway inhibition, offers new hope for patients at a high risk for basal cell cancer.

  8. Aging changes in skin

    Science.gov (United States)

    ... Stress Other causes of skin changes: Allergies to plants and other substances Climate Clothing Exposures to industrial and household chemicals Indoor heating Sunlight can cause: Loss of elasticity (elastosis) ...

  9. [Skin-picking disorder].

    Science.gov (United States)

    Niemeier, V; Peters, E; Gieler, U

    2015-10-01

    The disorder is characterized by compulsive repetitive skin-picking (SP), resulting in skin lesions. The patients must have undertaken several attempts to reduce or stop SP. The disorder must have led to clinically significant limitations in social, professional, or other important areas of life. The symptoms cannot be better explained by another emotional disorder or any other dermatological disease. In the new DSM-V, skin-picking disorder has been included in the diagnostic system as an independent disorder and describes the self-injury of the skin by picking or scratching with an underlying emotional disorder. SP is classified among the impulse-control disorders and is, thus, differentiated from compulsive disorders as such. There are often emotional comorbidities. In cases of pronounced psychosocial limitation, interdisciplinary cooperation with a psychotherapist and/or psychiatrist is indicated.

  10. Skin picking disorder.

    Science.gov (United States)

    Grant, Jon E; Odlaug, Brian L; Chamberlain, Samuel R; Keuthen, Nancy J; Lochner, Christine; Stein, Dan J

    2012-11-01

    Although skin picking has been documented in the medical literature since the 19th century, only now is it receiving serious consideration as a DSM psychiatric disorder in discussions for DSM-5. Recent community prevalence studies suggest that skin picking disorder appears to be as common as many other psychiatric disorders, with reported prevalences ranging from 1.4% to 5.4%. Clinical evaluation of patients with skin picking disorder entails a broad physical and psychiatric examination, encouraging an interdisciplinary approach to evaluation and treatment. Approaches to treatment should include cognitive-behavioral therapy (including habit reversal or acceptance-enhanced behavior therapy) and medication (serotonin reuptake inhibitors, N-acetylcysteine, or naltrexone). Based on clinical experience and research findings, the authors recommend several management approaches to skin picking disorder.

  11. Designing pliable structural Skins

    DEFF Research Database (Denmark)

    Tamke, Martin; Peters, Brady; Nielsen, Stig Anton;

    2013-01-01

    Structural stability can be formed through structured or seemingly unstructured approaches to fold, plead or crumble paper. This paper reports on two projects that showcase how computational design approaches can help to widen the understanding and use of structural skins....

  12. Skin or nail culture

    Science.gov (United States)

    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, ...

  13. Skin, Hair, and Nails

    Science.gov (United States)

    ... Development Infections Diseases & Conditions Pregnancy & Baby Nutrition & Fitness Emotions & Behavior School & Family Life First Aid & Safety Doctors & ... produce melanin, the pigment that gives skin its color. All people have roughly the same number of ...

  14. An elastic second skin

    Science.gov (United States)

    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. Radiation therapy -- skin care

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000735.htm Radiation therapy - skin care To use the sharing features ... this page, please enable JavaScript. When you have radiation treatment for cancer, you may have some changes ...

  16. Allergy testing - skin

    Science.gov (United States)

    Patch tests - allergy; Scratch tests - allergy; Skin tests - allergy; RAST test; Allergic rhinitis - allergy testing; Asthma - allergy testing; Eczema - allergy testing; Hayfever - allergy testing; Dermatitis - allergy testing; Allergy testing; ...

  17. Scalded skin syndrome

    Science.gov (United States)

    ... Severe bloodstream infection ( septicemia ) Spread to deeper skin infection ( cellulitis ) When to Contact a Medical Professional Call your provider or go to the emergency room if you have symptoms of this disorder. Prevention ... Alternative Names Ritter disease; Staphylococcal ...

  18. Skin lesion biopsy

    Science.gov (United States)

    ... procedure will leave a small indented area. This type of biopsy is often done when a skin cancer is ... may have stitches to close the area. This type of biopsy is often done to diagnose rashes . EXCISIONAL BIOPSY ...

  19. Spiritual and religious aspects of skin and skin disorders

    Directory of Open Access Journals (Sweden)

    Shenefelt PD

    2014-08-01

    Full Text Available Philip D Shenefelt,1 Debrah A Shenefelt2 1Dermatology and Cutaneous Surgery, University of South Florida, Tampa, 2Congregation Or Ahavah, Lutz, FL, USA Abstract: 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. Keywords: skin, skin disorders, spiritual, religious

  20. Skin Diseases: Cross-section of human skin

    Science.gov (United States)

    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 ...

  1. Dermocosmetics for dry skin: a new role for botanical extracts.

    Science.gov (United States)

    Casetti, F; Wölfle, U; Gehring, W; Schempp, C M

    2011-01-01

    Dry skin is associated with a disturbed skin barrier and reduced formation of epidermal proteins and lipids. During recent years, skin-barrier-reinforcing properties of some botanical compounds have been described. Searching the PubMed database revealed 9 botanical extracts that specifically improve skin barrier and/or promote keratinocyte differentiation in vivo after topical application. The topical application of Aloe vera (leaf gel), Betula alba (birch bark extract), Helianthus annuus (sunflower oleodistillate), Hypericum perforatum (St. John's wort extract), Lithospermum erythrorhizon (root extract), Piptadenia colubrina (angico-branco extract) and Simarouba amara (bitter wood extract) increased skin hydration, reduced the transepidermal water loss, or promoted keratinocyte differentiation in humans in vivo. The topical application of Rubia cordifolia root extract and rose oil obtained from Rosa spp. flowers stimulated keratinocyte differentiation in mouse models. The underlying mechanisms of these effects are discussed. It is concluded that some botanical compounds display skin-barrier-reinforcing properties that may be used in dermocosmetics for dry skin. However, more investigations on the mode of action and more vehicle-controlled studies are required.

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

    Science.gov (United States)

    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.

  3. Mantoux Tuberculin Skin Test

    Centers for Disease Control (CDC) Podcasts

    2006-11-22

    Learn how to evaluate people for latent TB infection with the Mantoux tuberculin skin test. This podcast includes sections on administering and reading the Mantoux tuberculin skin test, the standard method for detecting latent TB infection since the 1930s.  Created: 11/22/2006 by National Center for HIV, STD and TB Prevention (NCHHSTP).   Date Released: 12/12/2006.

  4. Nicotinamide and the skin.

    Science.gov (United States)

    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. DOSHIC PHYSIOLOGY OF SKIN

    Directory of Open Access Journals (Sweden)

    Shivprasad Chiplunkar

    2013-06-01

    Full Text Available The balance of dosha  represents the healthy state and imbalance will cause various diseases. In normalcy doshas will be performing their own functions and individual doshas will be having their own specific sites. By telling the various sthana of each dosha, different function that is taken up by individual dosha in different sites has been highlighted.By mentioning ‘sparshanendriyam’ as one of the sthana of vata dosha the sensory functions of skin to vata dosha has been emphasised. By mentioning ‘sparshanam’ as one of the sthana of pittadosha, the function of colouring/pigmentation of skin, which is majorly carried out  by melanocytes by secreting melanin pigment has been highlighted. Meda is one among the sthanas of kapha dosha; this can be considered as the adipose tissue of skin/below skin. Since sweda is mala of meda it can be also considered as the secretions from the eccrine glands.With respect to skin, sensory functions, both tactile and thermal is carried out by vata dosha more specifically vyana vata, pigmentation to the skin carried out by meloncytes by secreting melanin, it is nothing but function of pitta dosha more specifically brajaka pitta with the help of udana vata and finally production of sweat in sweat glands is the function of kapha. So there is the need for further study and research regarding the sthanas of all three doshas in different structures/organs in the body and its physiology.

  6. Ultraflexible organic photonic skin.

    Science.gov (United States)

    Yokota, Tomoyuki; Zalar, Peter; Kaltenbrunner, Martin; Jinno, Hiroaki; Matsuhisa, Naoji; Kitanosako, Hiroki; Tachibana, Yutaro; Yukita, Wakako; Koizumi, Mari; Someya, Takao

    2016-04-01

    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.

  7. Efficient in vivo gene transfer to xenotransplanted human skin by lentivirus-mediated, but not by AAV-directed, gene delivery

    DEFF Research Database (Denmark)

    Jakobsen, Maria Vad; Askou, Anne Louise; Dokkedahl, Karin Stenderup

    Skin is an easily accessible organ, and therapeutic gene transfer to skin remains an attractive alternative for treatment of skin diseases. We compared the potential usefulness of various serotypes of recombinant AAV vectors and lentiviral vectors for gene transfer to human skin in a xenotranspla...... graft only. The study demonstrates limited capacity of single-stranded AAV vectors of six commonly used serotypes for gene delivery to human skin in vivo.......Skin is an easily accessible organ, and therapeutic gene transfer to skin remains an attractive alternative for treatment of skin diseases. We compared the potential usefulness of various serotypes of recombinant AAV vectors and lentiviral vectors for gene transfer to human skin...... in a xenotransplanted mouse model. Vector constructs encoding firefly luciferase were packaged in AAV capsids of serotype 1, 2, 5, 6, 8, and 9 and separately administered by intradermal injection in human skin transplants. For all serotypes, live bioimaging demonstrated low levels of transgene expression in the human...

  8. Stable Skin-specific Overexpression of Human CTLA4-Ig in Transgenic Mice through Seven Generations

    Institute of Scientific and Technical Information of China (English)

    Yong WANG; Yong NI; Hong WEI; Feng-Chao WANG; Liang-Peng GE; Xiang GAO

    2006-01-01

    Skin graft rejection is a typical cellular immune response, mainly mediated by T cells. Cytotoxic T lymphocyte associated antigen 4-immunoglobin (CTLA4-Ig) extends graft survival by blocking the T cell co-stimulation pathway and inhibiting T cell activation. To investigate the efficacy of CTLA4-Ig in prolonging skin graft survival, human CTLA4-Ig (hCTLA4-Ig) was engineered to overexpress in mouse skin by transgenesis using the K14 promoter. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay indicated that the expression of CTLA4-Ig remained skin-specific and relatively constant compared to the internal control protein, AKT, through seven generations. The presence and concentration of the hCTLA4-Ig protein in transgenic mouse sera was determined by enzyme-linked immunosorbent assay (ELISA), and the results indicated that the serum CTLA4-Ig concentration also remained constant through generations. Survival of transgenic mouse skins grafted onto rat wounds was remarkably prolonged compared to that of wild-type skins from the same mouse strain, and remained comparable among all seven generations. This suggested that the bioactive hCTLA4-Ig protein was stably expressed in transgenical mice through at least seven generations, which was consistent with the stable skin-specific CTLA4-Ig expression.The results demonstrated that the transgenic expression of hCTLA4-Ig in skin driven by the K14 promoter remained constant through generations, and a transgenic line can be established to provide transgenic skin with extended survival reproducibly.

  9. DCP-LA Exerts an Antiaging Action on the Skin.

    Science.gov (United States)

    Nishizaki, Tomoyuki

    2016-01-01

    The present study assessed the possibility for the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) as an antiaging compound for the skin by assaying senescence-associated β-galactosidase (SA-β-Gal), a biomarker of senescence and cell viability. The nitric oxide (NO) donor sodium nitroprusside (SNP) increased in SA-β-Gal-positive cells in cultured human fibroblasts and mouse keratinocytes, and DCP-LA significantly inhibited the effect of SNP. Moreover, SNP induced cell death in cultured mouse keratinocytes, and DCP-LA significantly prevented NO stress-induced death of keratinocytes. Taken together, these results indicate that DCP-LA exerts an antiaging action on the skin.

  10. Molecular genetic basis for the rhino mouse from Chinese KM subcolony

    Institute of Scientific and Technical Information of China (English)

    TIAN Ming; XIONG Yuliang; WANG Wanyu; ZHANG Yaping

    2004-01-01

    Both the rhino mouse and hairless mouse resulted from hairless gene mutation, but they show different phenotypes of skin physiology. The rhino mouse has more similar histological characters to human papular alopecia. Therefore rhino mouse is a good experimental animal model for human papular alopecia. This study reports a hairless mouse named rhino KIZ, arose from KM colony in Kunming Institue of Zoology, by systematic studies on morphology, skin histopathology, gene sequence, pedigree and protein domain analysis. The results demonstrate that a C-to-T transition in exon 11 of hr gene (The mutant gene has been applied for a Chinese patent (patent No. 03135280)) results in the rhino KIZ. The rhino KIZ with clear genetic mechanism will be a useful animal model.

  11. Recent Progress in Electronic Skin

    OpenAIRE

    Wang, Xiandi; Dong, Lin; Zhang, Hanlu; Yu, Ruomeng; Pan, Caofeng; 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 co...

  12. Skin aging and oxidative stress

    OpenAIRE

    Sayeeda Ahsanuddin; Minh Lam; Baron, Elma D.

    2016-01-01

    Skin aging occurs through two main pathways, intrinsic and extrinsic. These pathways have significant interaction in contributing to the aging phenotype, which includes skin laxity, wrinkling, pigmentation irregularities, and the appearance of neoplastic skin lesions. Here, we review the critical role that oxidative stress plays in skin aging, including its effects on signaling pathways involved in skin matrix formation and degradation, proteasome activity, as well as DNA structure. Furthermo...

  13. Skin involvement in Dupuytren's disease.

    OpenAIRE

    Wade, R.; Igali, L; Figus, A

    2016-01-01

    Whether the palmar skin has a role in the development, propagation or recurrence of Dupuytren's disease remains unclear. Clinical assessment for skin involvement is difficult and its correlation with histology uncertain. We prospectively biopsied the palmar skin of consecutive patients undergoing single digit fasciectomy (for primary Dupuytren's disease without clinically involved skin) and dermofasciectomy (for clinically involved skin or recurrence) in order to investigate this relationship...

  14. Spiritual and religious aspects of skin and skin disorders

    Science.gov (United States)

    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

  15. Mammalian skin cell biology: at the interface between laboratory and clinic.

    Science.gov (United States)

    Watt, Fiona M

    2014-11-21

    Mammalian skin research represents the convergence of three complementary disciplines: cell biology, mouse genetics, and dermatology. The skin provides a paradigm for current research in cell adhesion, inflammation, and tissue stem cells. Here, I discuss recent insights into the cell biology of skin. Single-cell analysis has revealed that human epidermal stem cells are heterogeneous and differentiate in response to multiple extrinsic signals. Live-cell imaging, optogenetics, and cell ablation experiments show skin cells to be remarkably dynamic. High-throughput, genome-wide approaches have yielded unprecedented insights into the circuitry that controls epidermal stem cell fate. Last, integrative biological analysis of human skin disorders has revealed unexpected functions for elements of the skin that were previously considered purely structural.

  16. Sprayed skin turbine component

    Science.gov (United States)

    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. Extreme skin depth waveguides

    CERN Document Server

    Jahani, Saman

    2014-01-01

    Recently, we introduced a paradigm shift in light confinement strategy and introduced a class of extreme skin depth (e-skid) photonic structures (S. Jahani and Z. Jacob, "Transparent sub-diffraction optics: nanoscale light confinement without metal," Optica 1, 96-100 (2014)). Here, we analytically establish that figures of merit related to light confinement in dielectric waveguides are fundamentally tied to the skin depth of waves in the cladding. We contrast the propagation characteristics of the fundamental mode of e-skid waveguides and conventional waveguides to show that the decay constant in the cladding is dramatically larger in e-skid waveguides, which is the origin of sub-diffraction confinement. Finally, we propose an approach to verify the reduced skin depth in experiment using the decrease in the Goos-H\\"anchen phase shift.

  18. Skin Cancer Detection

    Directory of Open Access Journals (Sweden)

    N. Durga Rao

    2016-06-01

    Full Text Available : In recent days, skin cancer is seen as one of the most Hazardous form of the Cancers found in Humans. Skin cancer is found in various types such as Melanoma, Basal and Squamous cell Carcinoma among which Melanoma is the most unpredictable. The detection of Melanoma cancer in early stage can be helpful to cure it. Computer vision can play important role in Medical Image Diagnosis and it has been proved by many existing systems. In this paper, we present a survey on different steps which are being to detect the Melanoma Skin Cancer using Image Processing tools. In every step, what are the different methods are be included in our paper

  19. Smoking and skin disease

    DEFF Research Database (Denmark)

    Thomsen, S F; Sørensen, L T

    2010-01-01

    Tobacco smoking is a serious and preventable health hazard that can cause or exacerbate a number of diseases and shorten life expectancy, but the role of smoking as an etiologic factor in the development of skin disease is largely unknown. Although epidemiological evidence is sparse, findings...... suggest that tobacco smoking is a contributing factor in systemic lupus erythematosus, psoriasis, palmoplantar pustulosis, cutaneous squamous cell carcinoma, hidradenitis suppurativa, and genital warts. In contrast, smoking may confer some protective effects and mitigate other skin diseases, notably...... pemphigus vulgaris, pyoderma gangrenosum, aphthous ulcers, and Behçet's disease. Various degenerative dermatologic conditions are also impacted by smoking, such as skin wrinkling and dysregulated wound healing, which can result in post-surgical complications and delayed or even arrested healing of chronic...

  20. Skin tears: prevention and treatment.

    Science.gov (United States)

    Wick, Jeannette Y; Zanni, Guido R

    2008-07-01

    While skin tears are common among the elderly in general, and residents of long-term care facilities in particular, there has been limited research into their treatment. Many facilities voluntarily track skin tears, and some states require facilities to report these events. Risk factors include age, xerosis (abnormal eye, skin, or mouth dryness), need for help in activities of daily living, presence of senile purpura, visual impairment, and poor nutrition. Plans to prevent skin tears that employ skin sleeves, padded side rails, gentle skin cleansers, moisturizing lotions, as well as staff education, can decrease by half the number of skin tears incurred in a long-term care facility. Although the treatment process seems simple, it is time consuming and can be painful for the patient. Residents with dementia or agitation often try to remove bulky dressings used to cover skin tears. Dressing changes may injure the fragile wound via skin stripping.

  1. Radiosensitivity of keratinocytes from tongue and skin; enhanced radioresistance following serial cultivation

    Energy Technology Data Exchange (ETDEWEB)

    Parkinson, E.K.; Hume, W.J.; Potten, C.S.

    1986-01-01

    A study has been carried out of the radiation response of keratinocytes from human skin, mouse skin and mouse tongue to 0-10 Gy of ..gamma..-radiation, carried out in suspension at 20/sup 0/C. The Dsub(o)values for primary cultures of keratinocytes was similar to those obtained in vivo for mice, suggesting that this in vitro assay could be used to measure the sensitivity of keratinocytes treated with various cytotoxic agents. Sensitivity appears to change on subculturing and hence subcultures may be less appropriate for determining in vivo cell sensitivities.

  2. Real-time in vivo imaging collagen in lymphedematous skin using multiphoton microscopy.

    Science.gov (United States)

    Wu, Xiufeng; Zhuo, Shuangmu; Chen, Jianxin; Liu, Ningfei

    2011-01-01

    Changes of dermal collagen are characteristic for chronic lymphedema. To evaluate these changes, a real-time imaging based on two-photon excited fluorescence and second-harmonic generation was developed for investigating collagen of lymphedematous mouse and rat tail skin in vivo. Our findings showed that the technique could image the morphological changes and distribution of collagen in lymphedematous mouse and rat tail skin in vivo. More importantly, it may allow visualization of dynamic collagen alteration during the progression of lymphedema. Our findings demonstrated that multiphoton microscopy may have potential in a clinical setting as an in vivo diagnostic and monitoring system for therapy in lymphology.

  3. The Knockout Mouse Project

    OpenAIRE

    Austin, Christopher P.; Battey, James F.; Bradley, Allan; Bucan, Maja; Capecchi, Mario; Collins, Francis S; Dove, William F.; Duyk, Geoffrey; Dymecki, Susan; Eppig, Janan T.; Grieder, Franziska B.; Heintz, Nathaniel; Hicks, Geoff; Insel, Thomas R; Joyner, Alexandra

    2004-01-01

    Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and e...

  4. Skin innate immune system

    Directory of Open Access Journals (Sweden)

    Berna Aksoy

    2013-06-01

    Full Text Available All multicellular organisms protect themselves from external universe and microorganisms by innate immune sytem that is constitutively present. Skin innate immune system has several different components composed of epithelial barriers, humoral factors and cellular part. In this review information about skin innate immune system and its components are presented to the reader. Innate immunity, which wasn’t adequately interested in previously, is proven to provide a powerfull early protection system, control many infections before the acquired immunity starts and directs acquired immunity to develop optimally

  5. Study of surfactant-skin interactions by skin impedance measurements.

    Science.gov (United States)

    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.

  6. Liquid Crystal Gel Reduces Age Spots by Promoting Skin Turnover

    Directory of Open Access Journals (Sweden)

    Mina Musashi

    2014-07-01

    Full Text Available Studies have shown that liquid crystals structurally resembling the intercellular lipids in the stratum corneum can beneficially affect the skin when applied topically by stimulating the skin’s natural regenerative functions and accelerating epidermal turnover. In the present study, the effects of applying low concentrations of a liquid crystal gel of our own creation were evaluated using epidermal thickening in mouse skin as an assay for effective stimulation of epidermal turnover. A liquid crystal gel was also applied topically to human facial skin, and analysis was conducted using before-and-after photographs of age spots, measurements of L* values that reflect degree of skin pigmentation, single-layer samples of the stratum corneum obtained via tape-stripping, and measurements of trans-epidermal water loss that reflect the status of the skin’s barrier function. The results suggested that cost-effective creams containing as low as 5% liquid crystal gel might be effective and safely sold as skin care products targeting age spots and other problems relating to uneven skin pigmentation.

  7. Replacing the computer mouse

    OpenAIRE

    Dernoncourt, Franck

    2014-01-01

    In a few months the computer mouse will be half-a-century-old. It is known to have many drawbacks, the main ones being: loss of productivity due to constant switching between keyboard and mouse, and health issues such as RSI. Like the keyboard, it is an unnatural human-computer interface. However the vast majority of computer users still use computer mice nowadays. In this article, we explore computer mouse alternatives. Our research shows that moving the mouse cursor can be done efficiently ...

  8. Method for Obtaining Committed Adult Mesenchymal Precursors from Skin and Lung Tissue

    OpenAIRE

    Aurora Bernal; María Fernández; Pérez, Laura M.; Nuria San Martín; Gálvez, Beatriz G.

    2012-01-01

    AIMS: The present study reports an easy and efficient method for obtaining adult mesenchymal precursors from different adult mouse tissues. MATERIALS AND METHODS: We describe the isolation and expansion of mesenchymal precursors from skin and lung by a non-enzymatic method. Skin and lung mesenchymal precursors isolated by a modified explant technique were characterized in vitro by defined morphology and by a specific gene expression profile and surface markers. RESULTS AND CONCLUSIONS: Our re...

  9. The Tumor Suppressor Actions of the Vitamin D Receptor in Skin

    Science.gov (United States)

    2014-10-01

    Vitamin D Receptor in Skin PRINCIPAL INVESTIGATOR: Daniel D. Bikle, M.D., Ph.D. CONTRACTING ORGANIZATION: Northern California Institute for...SUBTITLE The Tumor Suppressor Actions of the Vitamin D Receptor in Skin 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0235 5c. PROGRAM...13. SUPPLEMENTARY NOTES 14. ABSTRACT The epidermis of the mouse lacking the vitamin D receptor (VDR) is susceptible to chemical and UVB

  10. CD69 modulates sphingosine-1-phosphate-induced migration of skin dendritic cells

    OpenAIRE

    Lamana, Amalia; Martin, Pilar; de la Fuente, Hortensia; Martinez-Muñoz, Laura; Cruz-Adalia, Aranzazu; Ramirez-Huesca, Marta; Escribano, Cristina; Gollmer, Kathrin; Mellado, Mario; Stein, Jens V.; Rodriguez-Fernandez, Jose Luis; Sanchez-Madrid, Francisco; del Hoyo, Gloria Martinez

    2011-01-01

    In this study, we have investigated the role of CD69, an early inducible leukocyte activation receptor, in murine dendritic cell (DC) differentiation, maturation, and migration. Skin DCs and DC subsets present in mouse lymphoid organs express CD69 in response to maturation stimuli. Using a contact sensitization model, we show that skin DCs migrated more efficiently to draining lymph nodes (LNs) in the absence of CD69. This was confirmed by subcutaneous transfer of CD69–/– DCs, which presented...

  11. Organotypic cocultures as skin equivalents: A complex and sophisticated in vitro system

    Directory of Open Access Journals (Sweden)

    Stark Hans-Jürgen

    2004-01-01

    Full Text Available To assess the role of genes required for skin organogenesis, tissue regeneration and homeostasis, we have established in vitro skin equivalents composed of primary cells or cell lines, respectively. In these organotypic cocultures keratinocytes generate a normal epidermis irrespective of the species and tissue origin of fibroblasts. The combination of cells derived from mouse and human tissues facilitates the identification of the origin of compounds involved in epidermal tissue reconstitution and thus the precise analysis of growth regulatory mechanisms.

  12. An encyclopedia of mouse DNA elements (Mouse ENCODE).

    Science.gov (United States)

    Stamatoyannopoulos, John A; Snyder, Michael; Hardison, Ross; Ren, Bing; Gingeras, Thomas; Gilbert, David M; Groudine, Mark; Bender, Michael; Kaul, Rajinder; Canfield, Theresa; Giste, Erica; Johnson, Audra; Zhang, Mia; Balasundaram, Gayathri; Byron, Rachel; Roach, Vaughan; Sabo, Peter J; Sandstrom, Richard; Stehling, A Sandra; Thurman, Robert E; Weissman, Sherman M; Cayting, Philip; Hariharan, Manoj; Lian, Jin; Cheng, Yong; Landt, Stephen G; Ma, Zhihai; Wold, Barbara J; Dekker, Job; Crawford, Gregory E; Keller, Cheryl A; Wu, Weisheng; Morrissey, Christopher; Kumar, Swathi A; Mishra, Tejaswini; Jain, Deepti; Byrska-Bishop, Marta; Blankenberg, Daniel; Lajoie, Bryan R; Jain, Gaurav; Sanyal, Amartya; Chen, Kaun-Bei; Denas, Olgert; Taylor, James; Blobel, Gerd A; Weiss, Mitchell J; Pimkin, Max; Deng, Wulan; Marinov, Georgi K; Williams, Brian A; Fisher-Aylor, Katherine I; Desalvo, Gilberto; Kiralusha, Anthony; Trout, Diane; Amrhein, Henry; Mortazavi, Ali; Edsall, Lee; McCleary, David; Kuan, Samantha; Shen, Yin; Yue, Feng; Ye, Zhen; Davis, Carrie A; Zaleski, Chris; Jha, Sonali; Xue, Chenghai; Dobin, Alex; Lin, Wei; Fastuca, Meagan; Wang, Huaien; Guigo, Roderic; Djebali, Sarah; Lagarde, Julien; Ryba, Tyrone; Sasaki, Takayo; Malladi, Venkat S; Cline, Melissa S; Kirkup, Vanessa M; Learned, Katrina; Rosenbloom, Kate R; Kent, W James; Feingold, Elise A; Good, Peter J; Pazin, Michael; Lowdon, Rebecca F; Adams, Leslie B

    2012-08-13

    To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome.

  13. About Skin-to-Skin Care (Kangaroo Care)

    Science.gov (United States)

    ... 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 ...

  14. Intact skin and not stripped skin is crucial for the safety and efficacy of peanut epicutaneous immunotherapy (EPIT in mice

    Directory of Open Access Journals (Sweden)

    Mondoulet Lucie

    2012-11-01

    Full Text Available Abstract Background Epicutaneous immunotherapy (EPIT on intact skin with an epicutaneous delivery system has already been used in preclinical and clinical studies. In epicutaneous vaccination and immunotherapy, the stripping of skin before application of the allergen is suggested to facilitate the passage of allergen through immune cells. Objectives The aim of this study was to compare the immunological response induced by EPIT performed on intact and stripped skin in a mouse model of peanut allergy. Methods After oral sensitization with peanut and cholera toxin, BALB/c mice were epicutaneously treated using an epicutaneous delivery system (Viaskin® (DBV Technologies, Paris applied either on intact skin or on stripped skin. Following EPIT, mice received an exclusive oral peanut regimen, aimed at triggering esophageal and jejunal lesions. We assessed eosinophil infiltration by histology, mRNA expression in the esophagus, antibody levels and peripheral T-cell response. Results EPIT on intact skin significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines as well as esophageal eosinophilia (2.7 ± 0.9, compared to Sham 19.9 ± 1.5, p  Conclusions Epicutaneous allergen-specific immunotherapy needs the integrity of superficial layers of the stratum corneum to warranty safety of treatment and to induce a tolerogenic profile of the immune response.

  15. Preventing Skin Cancer

    Centers for Disease Control (CDC) Podcasts

    2016-05-18

    A man and a woman talk about how they’ve learned to protect their skin from the sun over the years. .  Created: 5/18/2016 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 5/18/2016.

  16. Cryoglobulin induced skin ulceration

    Directory of Open Access Journals (Sweden)

    Fatima Razvi

    2015-01-01

    Full Text Available Lupus Erythematosus (LE is a multi-organ auto-immune disease which results from complex interaction of genetic and environmental factors. The clinical spectrum ranges from minor cutaneous lesions to life threatening multi-organ dysfunction. The skin manifestations are variable and common and range from LE specific to LE non-specific cutaneous disease. Vasculitis is one of the most common non-specific skin lesion of Systemic lupus erythematosus (SLE and appears as purpuric lesions, infarcts along lateral nail folds, peripheral gangrene, sub-cutaneous nodules and ulcers. Mixed cryoglobulinaemia (type II is associated with connective tissue disorders including SLE. Skin manifestations are seen in 60-100% patients and are more common in females. The most common manifestation is palpable purpura of lower extremities seen in 30-100% which often is triggered in winter or on cold exposure. Skin infarction, hemorrhagic crusts and ulcers are seen in 25% of patients. Wide spread necrotic ulcers are seen in 10-25% of patients which are often exacerbated by cold.

  17. Tuberculin Skin Testing

    Science.gov (United States)

    ... the Facts Tuberculosis - The Connection between TB and HIV 12-Dose Regimen for Latent TB Infection-Patient Education Brochure Posters Mantoux Tuberculin Skin Test Wall Chart World TB Day Think TB Stop TB Reports & Articles Morbidity and Mortality Weekly Reports (MMWRs) DTBE Authored ...

  18. Immunopathology of skin lesions

    Directory of Open Access Journals (Sweden)

    Khan Nazoora

    2001-09-01

    Full Text Available A study was conducted on 130 patients suffering from skin lesions which included psoriasis, lichen planus, DLE, pemphigus, vitiligo and alopecia areata. Forty age-and-sex-matched healthy individuals served as control. Serum IgG, IgM, and circulating immune complexes (CIC were estimated. Significant increase in serum IgG (1937.2 ± 1030.43 mg% and IgM (232.12 ± 136.98 mg% was observed in all the skin lesions when compared with controls except in lichen planus where they were significantly lowered, values being 580.61± 77.35 mg% and 66.88 ± 6.59mg% respectively. CIC levels were significantly raised (P<0.00 1 in various skin lesions (40.49±23.29 when compared with controls (17.68± 3.21, but no significance was observed in lichen planus( 17.72 ± 4.28. Serum IgG, IgM and CIC were statistically significantly altered depending on the extent of the lesion and lowered significantly to almost normal values following treatment, thereby confirming the role of immunity in the pathogenesis of these skin disorders.

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

    Science.gov (United States)

    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.

  20. Skin color independent assessment of aging using skin autofluorescence

    NARCIS (Netherlands)

    Koetsier, M.; Nur, E.; Chunmao, H.; Lutgers, H.L.; Links, T.P.; Smit, A.J.; Rakhorst, G.; de Graaff, R.

    2010-01-01

    Skin autofluorescence (AF) for the non-invasive assessment of the amount of accumulated tissue Advanced Glycation Endproducts (AGEs) increases with aging. In subjects with darker skin colors, measurements typically result in lower AF values than in subjects with fair skin colors, e. g. due to select

  1. 阻滞血管紧张素Ⅱ1型受体对创面愈合的影响%Effect of blocking angiotensin Ⅱ type 1 receptor on wound healing in mouse skin full-thickness injury model

    Institute of Scientific and Technical Information of China (English)

    李升红; 刘宏伟; 程飚; 徐媛; 肖静; 肖丽玲; 邵建立

    2012-01-01

    influenced wound healing.Methods Two full-thickness skin wounds were created on the dorsum of C57/BL6J mice.Animals were treated with or without AT1R blocker,Losartan at a dose of 20 mg/kg daily after wounding.Specimens were taken from the wound of each mouse on the day 3,5,7,9,11,13 and 15 after wounding.Reepitheliazation and granulation tissue formation in wounded skin tissue were evaluated by hematoxylin and eosin (HE) staining.The production of growth factors in wounded tissue during the healing process was detected by using enzyme linked immunosorbent assay (ELISA).Results Treatment with AT1R blocker,Losartan,significantly inhibited the rate of reepithelialization and the thickness of granulation tissue as compared with untreated group at the day 5 and 7 after wounding.Moreover,peritoneal application of Losartan decreased the production of epidermal growth factor (EGF),vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the wounded tissues at the indicated time after wounding.Conclusion These results indicate that AT1R blocker impaired wound healing at least partially via inhibiting growth factors production.

  2. Ocular Albinism Type 1 Regulates Melanogenesis in Mouse Melanocytes

    Directory of Open Access Journals (Sweden)

    Tianzhi Chen

    2016-09-01

    Full Text Available To investigate whether ocular albinism type 1 (OA1 is differentially expressed in the skin of mice with different coat colors and to determine its correlation with coat color establishment in mouse, the expression patterns and tissue distribution characterization of OA1 in the skin of mice with different coat colors were qualitatively and quantitatively analyzed by real-time quantitative PCR (qRT-PCR, immunofluorescence staining and Western blot. The qRT-PCR analysis revealed that OA1 mRNA was expressed in all mice skin samples tested, with the highest expression level in brown skin, a moderate expression level in black skin and the lowest expression level in gray skin. Positive OA1 protein bands were also detected in all skin samples by Western blot analysis. The relative expression levels of OA1 protein in both black and brown skin were significantly higher than that in gray skin, but there was no significant difference between black and brown mice. Immunofluorescence assays revealed that OA1 was mainly expressed in the hair follicle matrix, the inner and outer root sheath in the skin tissues with different coat colors. To get further insight into the important role of OA1 in the melanocytes’ pigmentation, we transfected the OA1 into mouse melanocytes and then detected the relative expression levels of pigmentation-related gene. Simultaneously, we tested the melanin content of melanocytes. As a result, the overexpression of OA1 significantly increased the expression levels of microphthalmia-associated transcription factor (MITF, tyrosinase (TYR, tyrosinase-related protein 1 (TRP1 and premelanosome protein (PMEL. However, the tyrosinase-related protein 2 (TRP2 level was attenuated. By contrast, the level of glycoprotein non-metastatic melanoma protein b (GPNMB was unaffected by OA1 overexpression. Furthermore, we observed a significant increase in melanin content in mouse melanocyte transfected OA1. Therefore, we propose that OA1 may

  3. SKIN DETECTION OF ANIMATION CHARACTERS

    Directory of Open Access Journals (Sweden)

    Kazi Tanvir Ahmed Siddiqui

    2015-02-01

    Full Text Available The increasing popularity of animes makes it vulnerable to unwanted usages like copyright violations and pornography. That’s why, we need to develop a method to detect and recognize animation characters. Skin detection is one of the most important steps in this way. Though there are some methods to detect human skin color, but those methods do not work properly for anime characters. Anime skin varies greatly from human skin in color, texture, tone and in different kinds of lighting. They also vary greatly among themselves. Moreover, many other things (for example leather, shirt, hair etc., which are not skin, can have color similar to skin. In this paper, we have proposed three methods that can identify an anime character’s skin more successfully as compared with Kovac, Swift, Saleh and Osman methods, which are primarily designed for human skin detection. Our methods are based on RGB values and their comparative relations.

  4. Tissue Engineered Human Skin Equivalents

    Directory of Open Access Journals (Sweden)

    Zheng Zhang

    2012-01-01

    Full Text Available Human skin not only serves as an important barrier against the penetration of exogenous substances into the body, but also provides a potential avenue for the transport of functional active drugs/reagents/ingredients into the skin (topical delivery and/or the body (transdermal delivery. In the past three decades, research and development in human skin equivalents have advanced in parallel with those in tissue engineering and regenerative medicine. The human skin equivalents are used commercially as clinical skin substitutes and as models for permeation and toxicity screening. Several academic laboratories have developed their own human skin equivalent models and applied these models for studying skin permeation, corrosivity and irritation, compound toxicity, biochemistry, metabolism and cellular pharmacology. Various aspects of the state of the art of human skin equivalents are reviewed and discussed.

  5. Eldercare at Home: Skin Problems

    Science.gov (United States)

    ... disorders that give rise to serious medical problems. Older skin is less oily, less elastic, and thinner. It ... of old age." Response Yes, it is true older skin is less oily and it is thinner than ...

  6. Skin - abnormally dark or light

    Science.gov (United States)

    ... ency/article/003242.htm Skin - abnormally dark or light To use the sharing features on this page, ... the hands. The bronze color can range from light to dark (in fair-skinned people) with the ...

  7. Maintaining Healthy Skin -- Part 2

    Science.gov (United States)

    ... from seams or elastic binding. Check also for blisters, bumps, insect bites, dry flaky skin or pimples. ... always check your skin carefully after wearing new shoes or clothing. Too loose — Loose clothing can form ...

  8. The management of skin tears.

    Science.gov (United States)

    Meuleneire, Frans

    During the ageing process the layers of the skin start to atrophy; the epidermis becomes thin and fragile, and dermal thickness decreases by 20 per cent (White et al, 1994). This makes skin tears a common problem among older people.

  9. Staining of skin with dihydroxyacetone.

    Science.gov (United States)

    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.

  10. Gaze beats mouse

    DEFF Research Database (Denmark)

    Mateo, Julio C.; San Agustin, Javier; Hansen, John Paulin

    2008-01-01

    Facial EMG for selection is fast, easy and, combined with gaze pointing, it can provide completely hands-free interaction. In this pilot study, 5 participants performed a simple point-and-select task using mouse or gaze for pointing and a mouse button or a facial-EMG switch for selection. Gaze...

  11. The MOUSE Squad

    Science.gov (United States)

    Borja, Rhea R.

    2004-01-01

    This article presents a New York city after-school program started by MOUSE (Making Opportunities for Upgrading Schools and Education), a national nonprofit group that teaches students how to fix computers, and equips them with the communication and problem-solving skills to help them in the working world. The MOUSE program is part of a trend…

  12. Nicotinamide for skin cancer chemoprevention.

    Science.gov (United States)

    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.

  13. A REVIEW ON SKIN CANCER

    OpenAIRE

    S. Ramya Silpa; Chidvila V

    2013-01-01

    Skin cancer can be of 2 types mainly. They are malignant melanoma and non-malignant melanoma. Skin cancer mainly occurs due to exposure of sunlight. Ozone depletion and chemical exposures are other factors involved in precipitating skin cancer. Mutations of p53 gene are involved in UV- induced carcinogenesis. P53 gene acts vital in development of SCC. So, prevention of skin cancer is the main criteria. Regular application of sunscreens could be one of the primary prevention. The purpose of pr...

  14. Mouse genome database 2016.

    Science.gov (United States)

    Bult, Carol J; Eppig, Janan T; Blake, Judith A; Kadin, James A; Richardson, Joel E

    2016-01-01

    The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the primary community model organism database for the laboratory mouse and serves as the source for key biological reference data related to mouse genes, gene functions, phenotypes and disease models with a strong emphasis on the relationship of these data to human biology and disease. As the cost of genome-scale sequencing continues to decrease and new technologies for genome editing become widely adopted, the laboratory mouse is more important than ever as a model system for understanding the biological significance of human genetic variation and for advancing the basic research needed to support the emergence of genome-guided precision medicine. Recent enhancements to MGD include new graphical summaries of biological annotations for mouse genes, support for mobile access to the database, tools to support the annotation and analysis of sets of genes, and expanded support for comparative biology through the expansion of homology data.

  15. Diffuse scaling dermatitis in an athymic nude mouse.

    Science.gov (United States)

    Russo, M; Invernizzi, A; Gobbi, A; Radaelli, E

    2013-07-01

    This report describes the clinicopathological features of a case of diffuse scaling dermatitis that occurred in a 16-week-old female athymic nude (CrTac:NCr-Foxn1(nu)) mouse. Gross presentation was suggestive of Corynebacterium bovis infection (scaly skin disease). However, C. bovis was not isolated from the skin of the affected animal or from the skin of unaffected CrTac:NCr-Foxn1(nu) mice housed in the same cage or room. Staphylococcus xylosus was instead isolated in high numbers from the skin lesion, whereas only a few colonies were recovered from the skin of unaffected mice. Microscopically, the affected skin was characterized by chronic hyperplastic and hyperkeratotic dermatitis with focal ulcerations, extensive serocellular crusts, and intralesional clusters of Gram-positive coccoid bacteria. Although gross presentation of the reported case was suggestive of C. bovis infection, epidemiological, histopathological, and bacteriological findings definitively ruled out an outbreak of scaly skin disease. A diagnostic hypothesis of hyperplastic and hyperkeratotic dermatitis associated with opportunistic S. xylosus infection was formulated based on increased bacterial burden and presence of intralesional Gram-positive coccoid bacteria.

  16. Skin cancer: Etiology and management.

    Science.gov (United States)

    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.

  17. Skin Pedagogies and Abject Bodies

    Science.gov (United States)

    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. Antioxidant Therapies for Ulcerative Dermatitis: A Potential Model for Skin Picking Disorder.

    Science.gov (United States)

    George, Nneka M; Whitaker, Julia; Vieira, Giovana; Geronimo, Jerome T; Bellinger, Dwight A; Fletcher, Craig A; Garner, Joseph P

    2015-01-01

    Skin Picking Disorder affects 4% of the general population, with serious quality of life impacts, and potentially life threatening complications. Standard psychoactive medications do not help most patients. Similarly, Mouse Ulcerative Dermatitis (skin lesions caused by excessive abnormal grooming behavior) is very common in widely used inbred strains of mice, and represents a serious animal welfare issue and cause of mortality. Treatment options for Ulcerative Dermatitis are largely palliative and ineffective. We have proposed mouse Ulcerative Dermatitis as a model for human Skin Picking Disorder based on similar epidemiology, behavior, and its comorbidity and mechanistic overlap with hair pulling (trichotillomania). We predicted that mouse Ulcerative Dermatitis would be treated by N-Acetylcysteine, as this compound is highly effective in treating both Skin Picking Disorder and Trichotillomania. Furthermore, we hypothesized that N-Acetylcysteine's mode of action is as a precursor to the production of the endogenous antioxidant glutathione in the brain, and therefore intranasal glutathione would also treat Ulcerative Dermatitis. Accordingly, we show in a heterogenous prospective trial, the significant reduction in Ulcerative Dermatitis lesion severity in mice receiving either N-acetylcysteine (oral administration) or glutathione (intranasal). The majority of mice treated with N-acetylcysteine improved slowly throughout the course of the study. Roughly half of the mice treated with glutathione showed complete resolution of lesion within 2-4 weeks, while the remainder did not respond. These findings are the first to show that the use of N-acetylcysteine and Glutathione can be curative for mouse Ulcerative Dermatitis. These findings lend additional support for mouse Ulcerative Dermatitis as a model of Skin Picking Disorder and also support oxidative stress and glutathione synthesis as the mechanism of action for these compounds. As N-Acetylcysteine is poorly tolerated

  19. Serotonin in human skin

    Institute of Scientific and Technical Information of China (English)

    Jianguo Huang; Qiying Gong; Guiming Li

    2005-01-01

    In this review the authors summarize data of a potential role for serotonin in human skin physiology and pathology. The uncovering of endogenous serotonin synthesis and its transformation to melatonin underlines a putative important role of this pathway in melanocyte physiology and pathology. Pathways of the biosynthesis and biodegradation of serotonin have been characterized in human beings and its major cellular populations. Moreover, receptors of serotonin are expressed on keratinocytes, melanocytes, and fibroblasts and these mediate phenotypic actions on cellular proliferation and differentiation. And the widespread expression of a cutaneous seorotoninergic system indicates considerable selectivity of action to facilitate intra-, auto-, or paracrine mechanisms that define and influence skin function in a highly compartmentalized manner. Melatonin, in turn, can also act as a hormone, neurotransmitter, cytokine, biological modifier and immunomodulator. Thus, Serotonin local synthesis and cellular localization could thus become of great importance in the diagnosis and management of cutaneous pathology.

  20. Skin contamination dosimeter

    Science.gov (United States)

    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.

  1. Double-Skin Facade

    DEFF Research Database (Denmark)

    Kalyanova, Olena

    difficulties experienced by scientists when attempting to model DSF thermal and energy performance were examined. In addition, the lack of experimental studies and empirical validation of models was realized, many numerical models have not been empirically validated and most of them require an expert knowledge...... IEA Annex 34/43, subtask E "Double-Skin Facade". The results of empirical validation are discussed in this work. Discussion and analysis of experimental results is carried out. It has lead to hypothesis of recirculation flow phenomenon in the DSF cavity. Finally, a suggestion of a new numerical model......Double-Skin Facades (DSF) are gaining popularity that, in fact, appears to be independent from sturdy critics of the concept in the past years. DSF buildings are being built in Europe and worldwide, DSF concept is being taught at schools of architecture and fully glazed office buildings are being...

  2. Skin Cancer: Biology, Risk Factors & Treatment

    Science.gov (United States)

    ... 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 ...

  3. A Mouse Model of Hyperproliferative Human Epithelium Validated by Keratin Profiling Shows an Aberrant Cytoskeletal Response to Injury

    Directory of Open Access Journals (Sweden)

    Samal Zhussupbekova

    2016-07-01

    Full Text Available A validated animal model would assist with research on the immunological consequences of the chronic expression of stress keratins KRT6, KRT16, and KRT17, as observed in human pre-malignant hyperproliferative epithelium. Here we examine keratin gene expression profile in skin from mice expressing the E7 oncoprotein of HPV16 (K14E7 demonstrating persistently hyperproliferative epithelium, in nontransgenic mouse skin, and in hyperproliferative actinic keratosis lesions from human skin. We demonstrate that K14E7 mouse skin overexpresses stress keratins in a similar manner to human actinic keratoses, that overexpression is a consequence of epithelial hyperproliferation induced by E7, and that overexpression further increases in response to injury. As stress keratins modify local immunity and epithelial cell function and differentiation, the K14E7 mouse model should permit study of how continued overexpression of stress keratins impacts on epithelial tumor development and on local innate and adaptive immunity.

  4. Skin changes in menopause.

    Science.gov (United States)

    Bolognia, J L; Braverman, I M; Rousseau, M E; Sarrel, P M

    1989-12-01

    Skin signs and symptoms were examined in 46 menopausal women prior to estrogen replacement therapy. Several symptoms such as pruritus, bruising, dryness and thinning were seen more frequently in sun-exposed skin emphasizing the contribution of photoaging. At the end of a 6-mth treatment period, no significant difference was observed in the prevalence or severity of the cutaneous signs and symptoms when patients receiving transdermal 17 beta-estradiol (Estraderm) were compared with controls (the only exception was cutaneous flushing). Elastic fibers from sun-protected (buttock) skin of menopausal women were studied by light and electron microscopy. In 3 women (ages 30-37) with a history of premature menopause, the elastic fibers had several degenerative changes including coalescence of cystic spaces into lacunae, peripheral fragmentation, granular degeneration and splitting of the fibers into strands. Similar age-related ultrastructural changes are normally found in individuals that are at least 20 yrs older than these patients. These findings are suggestive of a relationship between premature aging of the dermal elastic fibers and estrogen deprivation.

  5. SKIN RADIATION IN PANORAMIC

    Directory of Open Access Journals (Sweden)

    Herry Irawan

    2015-06-01

    Full Text Available Dental panoramic radiograph in Indonesia has been widely used. Modern diagnostic imaging equipment with minimum radiation is still very limited. One of the conditions in nuclear safety law, UU 10/1997, is an optimization of all radiation sources with DRL through skin dose measurements. In Indonesia, the national DRL has not been established yet, and there were no reports on the study of panoramic skin dose in Indonesia. The aim of this preliminary study was to obtain a panoramic skin dose radiation as reference to establish DRL in Indonesia. Panoramic radiographs of sixteen female and fifteen male patients, aged 4 – 48 years, were taken using the standard conventional method, with TLD chips attached in location groups. The chips were then read with the detector and integrator of BATAN, in high and low temperature condition at the same time. It was revealed that behind the right and left ear were the regions with the highest radiation dose received, followed by the back of the neck, left jaw, right jaw, and chin. The result of this study has shown the importance of DRL in Indonesia since the use of modern diagnostic imaging equipement that limits radiation dose to the minimum level is still very limited.

  6. Development of human skin equivalents to unravel the impaired skin barrier in atopic dermatitis skin

    NARCIS (Netherlands)

    Eweje, M.O.

    2016-01-01

    The studies in this thesis describes the barrier defects in Atopic Dermatitis (AD) skin and various techniques to develop AD Human Skin Equivalents (HSEs) which can be used to better understand the role of several factors in the pathogenesis of AD skin. The results described show that Inflammation p

  7. Acute skin lesions following psoralen plus ultraviolet A radiation investigated by optical coherence tomography

    Science.gov (United States)

    Liu, Z. M.; Zhong, H. Q.; Zhai, J.; Wang, C. X.; Xiong, H. L.; Guo, Z. Y.

    2013-08-01

    Psoralen plus ultraviolet A radiation (PUVA) therapy is a very important clinical treatment of skin diseases such as vitiligo and psoriasis, but associated with an increased risk of skin photodamage, especially photoaging. In this work, optical coherence tomography (OCT), a novel non-invasive imaging technology, was introduced to investigate in vivo the photodamage induced by PUVA qualitatively and quantitatively. Balb/c mouse dorsal skin was treated with 8-methoxypsoralen (8-MOP), and then exposed to UVA radiation. OCT images of the tissues were obtained by an OCT system with a 1310 nm central wavelength. Skin thickness and the attenuation coefficient were extracted from the OCT images to analyze the degree of injury to mouse skin. The results demonstrated that PUVA-treated skin showed an increase in skin thickness, and a reduction of attenuation coefficient in the OCT signal compared with the control groups. The data also showed good correlation with the results observed in histological sections using hematoxylin and eosin staining. In conclusion, OCT is a promising tool for photobiological studies aimed at assessing the effect of PUVA therapy in vivo.

  8. Photothermal Radiometry for Skin Research

    Directory of Open Access Journals (Sweden)

    Perry Xiao

    2016-02-01

    Full Text Available Photothermal radiometry is an infrared remote sensing technique that has been used for skin and skin appendages research, in the areas of skin hydration, hydration gradient, skin hydration depth profiling, skin thickness measurements, skin pigmentation measurements, effect of topically applied substances, transdermal drug delivery, moisture content of bio-materials, membrane permeation, and nail and hair measurements. Compared with other technologies, photothermal radiometry has the advantages of non-contact, non-destructive, quick to make a measurement (a few seconds, and being spectroscopic in nature. It is also colour blind, and can work on any arbitrary sample surfaces. It has a unique depth profiling capability on a sample surface (typically the top 20 µm, which makes it particularly suitable for skin measurements. In this paper, we present a review of the photothermal radiometry work carried out in our research group. We will first introduce the theoretical background, then illustrate its applications with experimental results.

  9. Topical Treatment with Diclofenac, Calcipotriol (Vitamin-D3 Analog) and Difluoromethylornithine (DFMO) Does Not Prevent Nonmelanoma Skin Cancer in Mice

    DEFF Research Database (Denmark)

    Pommergaard, H C; Burcharth, J; Rosenberg, J

    2013-01-01

    Nonmelanoma skin cancer is a common cancer type with increasing incidence. The purpose of this study was to evaluate topical application of diclofenac, calcipotriol, and difluoromethylornithine as chemoprevention in a mouse model of ultraviolet light-induced skin tumors, since these agents have...

  10. Pig skin structure and transdermal delivery of liposomes: a two photon microscopy study

    DEFF Research Database (Denmark)

    Carrer, Dolores C.; Vermehren, Charlotte; Bagatolli, Luis

    2008-01-01

    that are in turn separated by particular structures we named "canyons". These canyons start in the surface as a wrinkle, eventually closing and going all the way inside the epidermis as a distinct structure that reaches the stratum basale. This structure, described previously in the epidermis of mouse skin...

  11. Therapeutic levels of erythropoietin (EPO) achieved after gene electrotransfer to skin in mice

    DEFF Research Database (Denmark)

    Gothelf, A; Hojman, P; Gehl, Julie

    2010-01-01

    Gene electrotransfer refers to gene transfection by electroporation and is an effective non-viral method for delivering naked DNA into cells and tissues. This study presents data from gene electrotransfer with erythropoietin (EPO) to mouse skin. Nine-week-old female NMRI mice received one, two...

  12. Development of human skin equivalents to unravel the impaired skin barrier in atopic dermatitis skin

    OpenAIRE

    Eweje, M.O.

    2016-01-01

    The studies in this thesis describes the barrier defects in Atopic Dermatitis (AD) skin and various techniques to develop AD Human Skin Equivalents (HSEs) which can be used to better understand the role of several factors in the pathogenesis of AD skin. The results described show that Inflammation plays a pivotal role in the development of epidermal and SC features of AD skin and that AD epidermal features can be maintained in vitro when AD skin biopsies are used to generate explant-HSEs. The...

  13. Percutaneous Absorption and Metabolism of Ketoprofen Isopropyl Ester via Excised Nude Mouse‘s and Monkey’s Skin

    Institute of Scientific and Technical Information of China (English)

    ZHUQuan-gang; HUJin-hong

    2003-01-01

    Aim:To study percutaneous absorption and metabolism of ketoprofen isopropyl ester (KPE)via excised nude mouse's and monkey's skin.Methods:Excised skin was prepared by surgical excision and enzyme digestion.Sideby-side diffusion cells were used for in vitro permeation studies.The concentrations of KPE and its metabolite in samples were assayed by HPLC.Results:All KPE penetration through whole thickness skin and stripped skin was metabolized to ketoprofen(KP).the concentration of which in the reciiver solution increased linearly with time.As to the nude mouse skin.the steady-state flux of KP through whole thickness skin was 2.5 times that of KPE through the whloe thickness skin,but the KP and KPE remaining in the whole thickness skin after the finishing of KPE penetration was 22.2 times in compered with the KP remaining in the whole thickness skin after the finshing of KP penetration.The rate of formation of the steady state KP from KPE throught dermis was significantly lower than that of KPE through the whole thickness skin.In he monkey skin,the rate of formation of the steady-state KP from KPE through the whole thickness skin was 0.7 times that from KPE through stripped skin.The KP and KPE remaining in the whole thickness skin after the finishing of KPE penetration was 2.0 time that in the stripped skin after the finishing of KPE penetration.The rate of fornation of the steady-state KP from KPE through dermis was lower than that from KPE through the whole thickness skin and the stripped skin.the KP remaining in dermis after the finsihing of KPE penetration was also significantly lower than the KP remaining in the whole thickness skin and the stripped skin after the finishing of KPE penetration.Conclusion:KP esters are of benefit to imporove the local action of KP.and skin esterase metabolism mainly develops in the epidermis.

  14. Interleukin-1, inflammasomes, autoinflammation and the skin.

    Science.gov (United States)

    Contassot, Emmanuel; Beer, Hans-Dietmar; French, Lars E

    2012-05-31

    Interleukin 1, one of the first cytokines discovered in the 1980s, and a potent mediator of fever, pain and inflammation, is at present experiencing a revival in biology and medicine. Whereas the mechanism of activation and secretion of interleukin 1β, which critically regulates the function of this molecule, has remained mysterious for some 30 years following its discovery, the identification of a new cytoplasmic complex of proteins regulating IL-1β activation and secretion has carried our understanding of the role of IL1 in biology and disease one big step further. The inflammasomes, recently identified innate immune complexes that sense intracellular danger- (e.g. uric acid, ATP, cytoplasmic DNA) or pathogen-associated molecular patterns (e.g. muramyl dipeptide, flagellin, anthrax lethal toxin), are now known to be responsible for triggering inflammation in response to several molecular patterns, including, for example, uric acid, a danger-associated molecular pattern and trigger of gout. Dysregulation of inflammasome function is however also the cause of a family of genetic autoinflammatory diseases known as cryopyrin-associated periodic syndromes (CAPS) characterised by recurrent episodes of fever, urticarial-like skin lesions, systemic inflammation and arthritis. In mouse models recapitulating mutations observed in CAPS, neutrophilic inflammation of the skin is a cardinal feature, in a manner similar to several autoinflammatory diseases with skin involvement such as PAPA (pyoderma gangrenosum, acne and pyogenic arthritis) and Schnitzler's syndrome, in which IL-1β very probably plays a pathogenic role. In this article the role of the inflammasome in IL-1 biology, autoinflammation and disease is reviewed, together with new avenues for the therapy of these diseases.

  15. Characterization of dendritic cells subpopulations in skin and afferent lymph in the swine model.

    Directory of Open Access Journals (Sweden)

    Florian Marquet

    Full Text Available Transcutaneous delivery of vaccines to specific skin dendritic cells (DC subsets is foreseen as a promising strategy to induce strong and specific types of immune responses such as tolerance, cytotoxicity or humoral immunity. Because of striking histological similarities between human and pig skin, pig is recognized as the most suitable model to study the cutaneous delivery of medicine. Therefore improving the knowledge on swine skin DC subsets would be highly valuable to the skin vaccine field. In this study, we showed that pig skin DC comprise the classical epidermal langerhans cells (LC and dermal DC (DDC that could be divided in 3 subsets according to their phenotypes: (1 the CD163(neg/CD172a(neg, (2 the CD163(highCD172a(pos and (3 the CD163(lowCD172a(pos DDC. These subtypes have the capacity to migrate from skin to lymph node since we detected them in pseudo-afferent lymph. Extensive phenotyping with a set of markers suggested that the CD163(high DDC resemble the antibody response-inducing human skin DC/macrophages whereas the CD163(negCD172(low DDC share properties with the CD8(+ T cell response-inducing murine skin CD103(pos DC. This work, by showing similarities between human, mouse and swine skin DC, establishes pig as a model of choice for the development of transcutaneous immunisation strategies targeting DC.

  16. Sesamol-loaded solid lipid nanoparticles for treatment of skin cancer.

    Science.gov (United States)

    Geetha, T; Kapila, Meenakshi; Prakash, Om; Deol, Parneet Kaur; Kakkar, Vandita; Kaur, Indu Pal

    2015-02-01

    Abstract Role of reactive oxygen species (ROS) in skin carcinogenesis is well documented. Natural molecules, like sesamol, with marked antioxidant potential can be useful in combating skin cancers. In vitro antiproliferative (using MTT assay) and DNA fragmentation studies in HL 60 cell lines, confirmed the apoptotic nature of sesamol. However, it showed a significant flux across the mice skin upon topical application, such that its local availability in skin is limited. Former is attributed mainly to its properties like small size, low molecular weight (138.28), and a sufficient lipid and water solubility (log P 1.29; solubility 38.8 mg/ml). To achieve its maximum epicutaneous delivery, packaging it into a suitable carrier system is thus indicated. Sesamol-loaded solid lipid nanoparticles (S-SLN) were thus prepared with particle size of 127.9 nm (PI: 0.256) and entrapment efficiency of 88.21%. Topical application of S-SLN in a cream base indicated significant retention in the skin with minimal flux across skin as confirmed by the in-vivo skin retention and ex-vivo skin permeation studies. In vivo anticancer studies performed on TPA-induced and benzo(a)pyrene initiated tumour production (ROS mediated) in mouse epidermis showed the normalization (in histology studies) of skin cancers post their induction, upon treatment with S-SLN.

  17. Mouse Genome Informatics (MGI)

    Data.gov (United States)

    U.S. Department of Health & Human Services — MGI is the international database resource for the laboratory mouse, providing integrated genetic, genomic, and biological data to facilitate the study of human...

  18. Mouse Phenome Database (MPD)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Mouse Phenome Database (MPD) has characterizations of hundreds of strains of laboratory mice to facilitate translational discoveries and to assist in selection...

  19. Skin moisturization mechanisms: new data.

    Science.gov (United States)

    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.

  20. Pro/antioxidant status in murine skin following topical exposure to cumene hydroperoxide throughout the ontogeny of skin cancer.

    Science.gov (United States)

    Shvedova, A A; Kisin, E R; Murray, A; Kommineni, C; Vallyathan, V; Castranova, V

    2004-01-01

    Organic peroxides used in the chemical and pharmaceutical industries have a reputation for being potent skin tumor promoters and inducers of epidermal hyperplasia. Their ability to trigger free radical generation is critical for their carcinogenic properties. Short-term in vivo exposure of mouse skin to cumene hydroperoxide (Cum-OOH) causes severe oxidative stress and formation of spin-trapped radical adducts. The present study was designed to determine the effectiveness of Cum-OOH compared to 12-O-tetradecanoylphorbol-13-acetate (TPA) in the induction of tumor promotion in the mouse skin, to identify the involvement of cyclooxygenase-2 (COX-2) in oxidative metabolism of Cum-OOH in keratinocytes, and to evaluate morphological changes and outcomes of oxidative stress in skin of SENCAR mice throughout a two-stage carcinogenesis protocol. Dimethyl-benz[a]anthracene (DMBA)-initiated mice were treated with Cum-OOH (32.8 micro mol) or TPA (8.5 nmol) twice weekly for 20 weeks to promote papilloma formation. Skin carcinoma formed only in DMBA/Cum-OOH-exposed mice. Higher levels of oxidative stress and inflammation (as indicated by the accumulation of peroxidative products, antioxidant depletion, and edema formation) were evident in the DMBA/Cum-OOH group compared to DMBA/TPA treated mice. Exposure of keratinocytes (HaCaT) to Cum-OOH for 18 h resulted in expression of COX-2 and increased levels of PGE(2). Inhibitors of COX-2 efficiently suppressed oxidative stress and enzyme expression in the cells treated with Cum-OOH. These results suggest that COX-2-dependent oxidative metabolism is at least partially involved in Cum-OOH-induced inflammatory responses and thus tumor promotion.

  1. Climate change and skin.

    Science.gov (United States)

    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

  2. Epidemiology of skin cancer.

    Science.gov (United States)

    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

  3. Derivation of Human Skin Fibroblast Lines for Feeder Cells of Human Embryonic Stem Cells.

    Science.gov (United States)

    Unger, Christian; Felldin, Ulrika; Rodin, Sergey; Nordenskjöld, Agneta; Dilber, Sirac; Hovatta, Outi

    2016-02-03

    After the first derivations of human embryonic stem cell (hESC) lines on fetal mouse feeder cell layers, the idea of using human cells instead of mouse cells as feeder cells soon arose. Mouse cells bear a risk of microbial contamination, and nonhuman immunogenic proteins are absorbed from the feeders to hESCs. Human skin fibroblasts can be effectively used as feeder cells for hESCs. The same primary cell line, which can be safely used for up to 15 passages after stock preparations, can be expanded and used for large numbers of hESC derivations and cultures. These cells are relatively easy to handle and maintain. No animal facilities or animal work is needed. Here, we describe the derivation, culture, and cryopreservation procedures for research-grade human skin fibroblast lines. We also describe how to make feeder layers for hESCs using these fibroblasts.

  4. Skin and bones. I.

    Science.gov (United States)

    Orlow, S J; Watsky, K L; Bolognia, J L

    1991-08-01

    Skin disorders in which a radiograph may detect associated bony changes or abnormalities of calcification are discussed. They are grouped into eight categories: (1) inherited diseases (e.g., alkaptonuria, neurofibromatosis); (2) congenital disorders (e.g., Sturge-Weber and Proteus syndromes); (3) inflammatory conditions (e.g., dermatomyositis, sarcoidosis); (4) infections (e.g., dental sinus, syphilis); (5) neoplasias (e.g., histiocytosis, mastocytosis); (6) drug- and environment-induced (e.g., acroosteolysis, retinoid toxicity); (7) calcinosis cutis; and (8) osteoma cutis. Part I of our review discusses the first two categories.

  5. Skin and bones. II.

    Science.gov (United States)

    Orlow, S J; Watsky, K L; Bolognia, J L

    1991-09-01

    Skin disorders in which a radiograph may detect associated bony changes or abnormalities of calcification are discussed. They are grouped into eight categories: (1) inherited diseases (e.g., alkaptonuria, neurofibromatosis); (2) congenital disorders (e.g., Sturge-Weber and Proteus syndromes); (3) inflammatory conditions (e.g., dermatomyositis, sarcoidosis); (4) infections (e.g., dental sinus, syphilis); (5) neoplasias (e.g., histiocytosis, mastocytosis); (6) drug- and environment-induced (e.g., acroosteolysis, retinoid toxicity); (7) calcinosis cutis; and (8) osteoma cutis. The first part of this review, published in the August 1991 issue of this JOURNAL, dealt with the first two categories; part II discusses categories 3 through 8.

  6. Shedding skin and tears.

    Science.gov (United States)

    Hammlerschlag, Carl A

    2007-06-01

    I am a purported expert in change and personal growth; that's the work I do with patients, and what I lecture and write about. I say that growth has nothing to do with adding on; it's always about letting go. Alas, it's always easier to tell others how to welcome shedding their skins than it is for me to do it myself. Letting go of the old and familiar is a necessary prerequisite for growth, but it's hard to do because no matter how much we may know, we have to move on. It always makes us feel vulnerable, which can inspire fear.

  7. Is skin penetration a determining factor in skin sensitization ...

    Science.gov (United States)

    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 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 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

  8. Ultrastructure of Campylobacter jejuni in gamma-irradiated mouse jejunum

    Energy Technology Data Exchange (ETDEWEB)

    Sosula, L.; Nicholls, E.M.; Skeen, M.

    1988-04-01

    This paper describes the ultrastructure of intracellular elongated, transitional and coccoid forms of Campylobacter jejuni, in irradiated mouse jejunum infected both in vitro and in vivo and in cultured human skin fibroblasts. Jejunum of irradiated mouse incubated for 1 hour under conditions favorable to the organisms showed minimal tissue degeneration. The intracellular organisms in this material were free cytoplasmic forms showing inner membrane degeneration, loss of cytoplasmic granules, and absence of flagella. The diameter of the coccoids was up to four times that of the elongated forms, as in plate cultures. Intracellular organisms were not found in challenged unirradiated controls, indicating that irradiation of mouse cells may be required for intracellular infection with human strains of C jejuni. In contrast, challenged human fibroblasts contained typical elongated organisms in cytoplasmic vacuoles. These findings are discussed with reference to Campylobacter strain, host resistance, and natural animal and human Campylobacter infections.

  9. The 'beauty' of skin neurobiology.

    Science.gov (United States)

    Pincelli, C; Bonté, F

    2003-07-01

    The skin is the most densely innervated organ in the body and there is a close relationship between the skin and the nervous system. Most skin cells express receptors for neuromediators (NM) and skin cells themselves are an important source of NM. In particular, human keratinocytes synthesize neurotrophins and endorphins and express their receptors. In addition to neurotrophic activity, NM are involved in skin homeostasis, trophism and stress responses. NM released from keratinocytes also function in a paracrine fashion on other skin cells, such as Langerhans cells, melanocytes and fibroblasts. We discuss the influence of NM on these cells, which may be involved in major cosmetic problems like ageing, baldness and dyspigmentation. Based on this correlation, it seems reasonable to target neural factors for cosmetic purposes.

  10. Pathophysiological Study of Sensitive Skin.

    Science.gov (United States)

    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.

  11. Protecting the skin during thyroidectomy

    Directory of Open Access Journals (Sweden)

    Renan Bezerra Lira

    2014-01-01

    Full Text Available In this note we describe the standard technical maneuver used in our department to protect the skin during thyroidectomy in order to get the best aesthetic result. We use surgical gloves to protect the skin during these operations to reduce the negative impact of thermal trauma and mechanical retractors and energy delivery devices at the edges of the skin incised. This practice is effective, inexpensive, rapid, reproducible and showed no complication in our experience of over 2,500 thyroidectomies.

  12. Aging-like skin changes in metabolic syndrome model mice are mediated by mineralocorticoid receptor signaling.

    Science.gov (United States)

    Nagase, Takashi; Akase, Tomoko; Sanada, Hiromi; Minematsu, Takeo; Ibuki, Ai; Huang, Lijuan; Asada, Mayumi; Yoshimura, Kotaro; Nagase, Miki; Shimada, Tsutomu; Aburada, Masaki; Nakagami, Gojiro; Sugama, Junko

    2013-02-01

    Aging is accelerated, at least in part, by pathological condition such as metabolic syndrome (MetS), and various molecular pathways such as oxidative stress are common mediators of aging and MetS. We previously developed the aging-like skin model by single ultraviolet (UV) irradiation on the MetS model mice. Recent studies revealed that mineralocorticoid receptor (MR) signaling plays a pivotal role for various tissue inflammation and damages in MetS. Although previous studies reported that MR is expressed in the skin and that overexpression of MR in the skin resulted in the skin atrophy, the physiological or pathological functions of MR in the skin are not fully elucidated. Here, we show the involvement of MR signaling in the aging-like skin changes in our own model. Elevations of oxidative stress and inflammation markers were observed in the MetS mice, and the UV-evoked aging-like skin damages were attenuated by topical antioxidant. MR expression was higher in the MetS mouse skin, and notably, expression of its effecter gene Sgk1 was significantly upregulated in the aging-like skin in the UV-irradiated MetS mice. Furthermore, topical application of MR antagonist spironolactone suppressed Sgk1 expression, oxidative stress, inflammation, and the aging-like changes in the skin. The 2-week UV onto the non-MetS mice, the more usual photoaging model, resulted in the skin damages mostly equivalent to the MetS mice with single UV, but they were not associated with upregulation of MR signaling. Our studies suggested an unexpected role of MR signaling in the skin aging in MetS status.

  13. Skin decontamination: principles and perspectives.

    Science.gov (United States)

    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.

  14. HOX genes in the skin

    Institute of Scientific and Technical Information of China (English)

    YANG Mei; LI Qing-feng; ZHANG Feng

    2010-01-01

    @@ Deep skin wounds heal by scar formation with a loss of its original appearance, structure and function.However, when the same damage occurs to the skin of an early gestational fetus, complete regeneration can be observed. Despite significant research in the field of skin regeneration, many mysteries remain, such as the loss of wound healing ability with maturity, the differences in healing at different parts of the body, and the presence of hypertrophic scars and keloids in some races but not in others. The finding of HOX genes in the skin provides new explanations to these conundrums.

  15. The future of skin metagenomics.

    Science.gov (United States)

    Mathieu, Alban; Vogel, Timothy M; Simonet, Pascal

    2014-01-01

    Metagenomics, the direct exploitation of environmental microbial DNA, is complementary to traditional culture-based approaches for deciphering taxonomic and functional microbial diversity in a plethora of ecosystems, including those related to the human body such as the mouth, saliva, teeth, gut or skin. DNA extracted from human skin analyzed by sequencing the PCR-amplified rrs gene has already revealed the taxonomic diversity of microbial communities colonizing the human skin ("skin microbiome"). Each individual possesses his/her own skin microbial community structure, with marked taxonomic differences between different parts of the body and temporal evolution depending on physical and chemical conditions (sweat, washing etc.). However, technical limitations due to the low bacterial density at the surface of the human skin or contamination by human DNA still has inhibited extended use of the metagenomic approach for investigating the skin microbiome at a functional level. These difficulties have been overcome in part by the new generation of sequencing platforms that now provide sequences describing the genes and functions carried out by skin bacteria. These methodological advances should help us understand the mechanisms by which these microorganisms adapt to the specific chemical composition of each skin and thereby lead to a better understanding of bacteria/human host interdependence. This knowledge will pave the way for more systemic and individualized pharmaceutical and cosmetic applications.

  16. Infrared sensing based sensitive skin

    Institute of Scientific and Technical Information of China (English)

    CAO Zheng-cai; FU Yi-li; WANG Shu-guo; JIN Bao

    2006-01-01

    Developed robotics sensitive skin is a modularized, flexible, mini-type array of infrared sensors with data processing capabilities, which can be used to cover the body of a robot. Depending on the infrared sensors and periphery processing circuit, robotics sensitive skin can in real-time provide existence and distance information about obstacles for robots within sensory areas. The methodology of designing sensitive skin and the algorithm of a mass of IR data fusion are presented. The experimental results show that the multi-joint robot with this sensitive skin can work autonomously in an unknown environment.

  17. Norathyriol Suppresses Skin Cancers Induced by Solar Ultraviolet Radiation by Targeting ERK Kinases

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jixia; Malakhova, Margarita; Mottamal, Madhusoodanan; Reddy, Kanamata; Kurinov, Igor; Carper, Andria; Langfald, Alyssa; Oi, Naomi; Kim, Myoung Ok; Zhu, Feng; Sosa, Carlos P.; Zhou, Keyuan; Bode, Ann M.; Dong, Zigang (Cornell); (Guangdong); (UMM)

    2012-06-27

    Ultraviolet (UV) irradiation is the leading factor in the development of skin cancer, prompting great interest in chemopreventive agents for this disease. In this study, we report the discovery of norathyriol, a plant-derived chemopreventive compound identified through an in silico virtual screening of the Chinese Medicine Library. Norathyriol is a metabolite of mangiferin found in mango, Hypericum elegans, and Tripterospermum lanceolatum and is known to have anticancer activity. Mechanistic investigations determined that norathyriol acted as an inhibitor of extracellular signal-regulated kinase (ERK)1/2 activity to attenuate UVB-induced phosphorylation in mitogen-activated protein kinases signaling cascades. We confirmed the direct and specific binding of norathyriol with ERK2 through a cocrystal structural analysis. The xanthone moiety in norathyriol acted as an adenine mimetic to anchor the compound by hydrogen bonds to the hinge region of the protein ATP-binding site on ERK2. Norathyriol inhibited in vitro cell growth in mouse skin epidermal JB6 P+ cells at the level of G{sub 2}-M phase arrest. In mouse skin tumorigenesis assays, norathyriol significantly suppressed solar UV-induced skin carcinogenesis. Further analysis indicated that norathyriol mediates its chemopreventive activity by inhibiting the ERK-dependent activity of transcriptional factors AP-1 and NF-{kappa}B during UV-induced skin carcinogenesis. Taken together, our results identify norathyriol as a safe new chemopreventive agent that is highly effective against development of UV-induced skin cancer.

  18. Trophic skin ulceration of leprosy: skin and serum zinc concentrations.

    Science.gov (United States)

    Oon, B B; Khong, K Y; Greaves, M W; Plummer, V M

    1974-06-08

    Skin and serum zinc measurements have been made in patients with leprosy with and without trophic skin ulceration and in several other groups. Serum zinc concentrations were decreased in leprosy irrespective of the presence or absence of skin ulceration. Serum zinc concentrations in leprosy were also unrelated to smears positive for Mycobacterium leprae and to the clinical type of leprosy. Since a decrease of the serum zinc was also found in patients with dermatitis herpetiformis and pulmonary tuberculosis it seems likely that the decreased serum zinc in leprosy is a nonspecific metabolic consequence of chronic skin and internal disease. The mean skin zinc concentration in leprosy did not differ significantly from the corresponding value in control subjects, the lack of agreement between serum and skin concentrations being possibly related to the presence of nonexchangeable keratin-bound zinc in skin. Though the clinical significance of lowered serum zinc concentrations in leprosy is uncertain therapeutic trials of zinc treatment in leprosy with trophic skin ulceration seem justifiable.

  19. Hospital celebrates skin to skin contact to raise awareness.

    Science.gov (United States)

    2013-06-01

    NEONATAL nurses at Birmingham's City Hospital have been celebrating the benefits of skin to skin contact with premature babies. They held a week of celebrations in the unit last month, in which they promoted the kangaroo care technique and breastfeeding to parents.

  20. Improvement of skin wound healing in diabetic mice by kinin B2 receptor blockade.

    Science.gov (United States)

    Desposito, Dorinne; Chollet, Catherine; Taveau, Christopher; Descamps, Vincent; Alhenc-Gelas, François; Roussel, Ronan; Bouby, Nadine; Waeckel, Ludovic

    2016-01-01

    Impaired skin wound healing is a major medical problem in diabetic subjects. Kinins exert a number of vascular and other actions limiting organ damage in ischaemia or diabetes, but their role in skin injury is unknown. We investigated, through pharmacological manipulation of bradykinin B1 and B2 receptors (B1R and B2R respectively), the role of kinins in wound healing in non-diabetic and diabetic mice. Using two mouse models of diabetes (streptozotocin-induced and db/db mice) and non-diabetic mice, we assessed the effect of kinin receptor activation or inhibition by subtype-selective pharmacological agonists (B1R and B2R) and antagonist (B2R) on healing of experimental skin wounds. We also studied effects of agonists and antagonist on keratinocytes and fibroblasts in vitro. Levels of Bdkrb1 (encoding B1R) and Bdkrb2 (encoding B2R) mRNAs increased 1-2-fold in healthy and wounded diabetic skin compared with in non-diabetic skin. Diabetes delayed wound healing. The B1R agonist had no effect on wound healing. In contrast, the B2R agonist impaired wound repair in both non-diabetic and diabetic mice, inducing skin disorganization and epidermis thickening. In vitro, B2R activation unbalanced fibroblast/keratinocyte proliferation and increased keratinocyte migration. These effects were abolished by co-administration of B2R antagonist. Interestingly, in the two mouse models of diabetes, the B2R antagonist administered alone normalized wound healing. This effect was associated with the induction of Ccl2 (encoding monocyte chemoattractant protein 1)/Tnf (encoding tumour necrosis factor α) mRNAs. Thus stimulation of kinin B2 receptor impairs skin wound healing in mice. B2R activation occurs in the diabetic skin and delays wound healing. B2R blockade improves skin wound healing in diabetic mice and is a potential therapeutic approach to diabetic ulcers.

  1. Optical coherence tomography for imaging of skin and skin diseases

    DEFF Research Database (Denmark)

    Mogensen, Mette; Thrane, Lars; Jørgensen, Thomas Martini

    2009-01-01

    Optical coherence tomography (OCT) is an emerging imaging technology based on light reflection. It provides real-time images with up to 2-mm penetration into the skin and a resolution of approximately 10 μm. It is routinely used in ophthalmology. The normal skin and its appendages have been studied......, as have many diseases. The method can provide accurate measures of epidermal and nail changes in normal tissue. Skin cancer and other tumors, as well as inflammatory diseases, have been studied and good agreement found between OCT images and histopathological architecture. OCT also allows noninvasive...... monitoring of morphologic changes in skin diseases and may have a particular role in the monitoring of medical treatment of nonmelanoma skin cancer. The technology is however still evolving and continued technological development will necessitate an ongoing evaluation of its diagnostic accuracy. Several...

  2. Camera Mouse Including “Ctrl-Alt-Del” Key Operation Using Gaze, Blink, and Mouth Shape

    Directory of Open Access Journals (Sweden)

    Kohei Arai

    2013-04-01

    Full Text Available This paper presents camera mouse system with additional feature: "CTRL - ALT - DEL" key. The previous gaze-based camera mouse systems are only considering how to obtain gaze and making selection. We proposed gaze-based camera mouse with "CTRL - ALT - DEL" key. Infrared camera is put on top of display while user looking ahead. User gaze is estimated based on eye gaze and head pose. Blinking and mouth detections are used to create "CTR - ALT - DEL" key. Pupil knowledge is used to improve robustness of eye gaze estimation against different users. Also, Gabor filter is used to extract face features. Skin color information and face features are used to estimate head pose. The experiments of each method have done and the results show that all methods work perfectly. By implemented this system, troubleshooting of camera mouse can be done by user itself and makes camera mouse be more sophisticated.

  3. How to Choose the Best Skin Care Products

    Science.gov (United States)

    ... Lines and Forehead Furrows Hair Loss Hyperpigmentation Melasma Sagging Skin Scars Skin Growths Skin Lesions Spider Veins ... Lines and Forehead Furrows Hair Loss Hyperpigmentation Melasma Sagging Skin Scars Skin Growths Skin Lesions Spider Veins ...

  4. 7-Chloro-5-(4-hydroxyphenyl)-1-methyl-3-(naphthalen-2-ylmethyl)-4,5-dihydro-1H-benzo[b][1,4]diazepin-2(3H)-one (Bz-423), a benzodiazepine, suppresses keratinocyte proliferation and has antipsoriatic activity in the human skin-severe, combined immunodeficient mouse transplant model.

    Science.gov (United States)

    Bhagavathula, Narasimharao; Nerusu, Kamalakar C; Hanosh, Andrew; Aslam, Muhammad N; Sundberg, Thomas B; Opipari, Anthony W; Johnson, Kent; Kang, Sewon; Glick, Gary D; Varani, James

    2008-03-01

    7-Chloro-5-(4-hydroxyphenyl)-1-methyl-3-(naphthalen-2-ylmethyl)-4,5-dihydro-1H-benzo[b][1,4]diazepin-2(3H)-one (Bz-423) is a benzodiazepine that has cytotoxic and cytostatic activity against a variety of cells in vivo and in vitro. In the present study, we demonstrate that Bz-423 (formulated for topical delivery) reduces epidermal hyperplasia in human psoriatic skin after transplantation to severe, combined immunodeficient (scid) mice. Bz-423 also suppresses the hyperplasia that develops in nonpsoriatic human skin as a consequence of transplantation to scid mice. Proliferation of human epidermal keratinocytes in monolayer culture was suppressed by Bz-423 at concentrations of 0.5 to 2.0 muM (noncytotoxic concentrations). Keratinocyte growth inhibition was accompanied by increased oxidant generation in Bz-423-treated cells, and treatment with vitamin E along with Bz-423 reversed the growth inhibition. Growth inhibition was accompanied by a redistribution of beta-catenin from a cytoplasmic pool to the cell membrane and by reduced levels of c-myc and cyclin D1 (two molecules associated with Wnt pathway signaling). Several analogs of Bz-423 were examined for antiproliferative activity against human epidermal keratinocytes and human dermal fibroblasts in monolayer culture. Each of the analogs tested suppressed growth of both cell types, but in all cases, keratinocytes were more sensitive than fibroblasts. Two of the compounds were found to suppress epidermal hyperplasia induced with all-trans retinoic acid in organ cultures of human skin. Taken together, these data show that Bz-423 and certain analogs produce biological responses in skin cells in vitro and in vivo that are consistent with therapeutic goals for treating psoriasis or epidermal hyperplasia resulting from other causes.

  5. Pygmies, Giants, and Skins

    CERN Document Server

    Piekarewicz, J

    2012-01-01

    Understanding the equation of state (EOS) of neutron-rich matter is a central goal of nuclear physics that cuts across a variety of disciplines. Indeed, the limits of nuclear existence, the collision of energetic heavy ions, the structure of neutron stars, and the dynamics of core-collapse supernova all depend critically on the nuclear-matter EOS. In this contribution I focus on the EOS of cold baryonic matter with special emphasis on its impact on the structure, dynamics, and composition of neutron stars. In particular, I discuss how laboratory experiments on neutron skins as well as on Pygmy and Giant resonances can help us elucidate the structure of these fascinating objects.

  6. Visualizing the Peripheral Primo Vascular System in Mice Skin by Using the Polymer Mercox

    Directory of Open Access Journals (Sweden)

    Miroslav Stefanov

    2015-09-01

    Full Text Available Objectives: As the peripheral part of the primo vascular system (PVS is difficult to visualize, we used a vascular casting material Mercox injected directly into the skin to take advantage of a simple procedure to visualize PVS structures as primo vessels (PVs and primo nodes (PNs in the skin. Methods: Two colors of the polymer Mercox were injected into mouse skin. After a partial maceration of the whole body with potassium hydroperoxide solution, we anatomized it under a stereomicroscope to trace the Mercox that had been injected into the PVS. Results: Injection of Mercox directly into the skin allowed the PVs and the PNs to be visualized. This approach can fill the PVS when the material is ejected out of the PVs or PNs. The shapes, sizes, and topographic positions of the nodes and the vessels are the hallmarks used to identify the PVS in skin when Mercox is used as a tracer. Conclusion: The direct injection of the casting material Mercox into skin, with modified partial maceration procedures, is a promising method for visualizing the PVs and the PNs in the peripheral part of the PVS in skin. The polymer Mercox can penetrate through the primo pores of the primo vascular wall and fill the PVs and the PNs. The data prove that PVs and PNs exist on the hypodermal layer of the skin.

  7. Oral antibiotic treatment induces skin microbiota dysbiosis and influences wound healing.

    Science.gov (United States)

    Zhang, Meiling; Jiang, Ziwei; Li, Dongqing; Jiang, Deming; Wu, Yelin; Ren, Hongyan; Peng, Hua; Lai, Yuping

    2015-02-01

    Antibiotic treatment eliminates commensal bacteria and impairs mucosal innate immune defenses in the gut. However, whether oral antibiotic treatment could alter the composition of the microbiota on the skin surface and influence innate immune responses remains unclear. To test this, mice were treated with vancomycin for 7 days and then wounds were made on the back skin of the mice. Five days later, scar tissue from each mouse was collected for bacterial enumeration, the bacterial composition on the scar and unwounded skin was determined using 16S RNA gene-based pyrosequencing analysis, and skin around wounds was collected for RNA extraction. Compared with the control group, the overall density and composition of skin bacteria were altered, and the proportion of Staphylococcus-related sequences was reduced in the vancomycin-treated group. Moreover, vancomycin treatment decreased the expression of RegIIIγ and interleukin (IL)-17 in the wounded skin. Taken together, our data demonstrate that antibiotic treatment decreases the bacterial density and alters the bacterial composition in skin wounds, followed by a decrease in RegIIIγ expression, which may contribute to the delayed wound repair. Our findings also indicate that antibiotic therapy should be carefully considered in the treatment of skin injury.

  8. Spaceship with heat-isolating outer skin

    NARCIS (Netherlands)

    Van Baten, T.J.; Buursink, J.

    2002-01-01

    A spaceship provided with a skin layer and cooling member for the skin layer that comprises a liquid-holding layer provided behind the skin layer, with an empty space being present between the liquid holding layer and the skin layer, so as to prevent heat transfer due to conduction between the skin

  9. Mouse bladder wall injection.

    Science.gov (United States)

    Fu, Chi-Ling; Apelo, Charity A; Torres, Baldemar; Thai, Kim H; Hsieh, Michael H

    2011-07-12

    Mouse bladder wall injection is a useful technique to orthotopically study bladder phenomena, including stem cell, smooth muscle, and cancer biology. Before starting injections, the surgical area must be cleaned with soap and water and antiseptic solution. Surgical equipment must be sterilized before use and between each animal. Each mouse is placed under inhaled isoflurane anesthesia (2-5% for induction, 1-3% for maintenance) and its bladder exposed by making a midline abdominal incision with scissors. If the bladder is full, it is partially decompressed by gentle squeezing between two fingers. The cell suspension of interest is intramurally injected into the wall of the bladder dome using a 29 or 30 gauge needle and 1 cc or smaller syringe. The wound is then closed using wound clips and the mouse allowed to recover on a warming pad. Bladder wall injection is a delicate microsurgical technique that can be mastered with practice.

  10. Pain-induced skin autoimmunity

    OpenAIRE

    Odoardi, Francesca; Neuhuber, Winfried; Flügel, Alexander

    2014-01-01

    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.

  11. Hereditary skin diseases of hemidesmosomes

    NARCIS (Netherlands)

    Jonkman, MF

    1999-01-01

    Studies of hereditary blistering skin diseases (epidermolysis bullosa) and targeted gene mutation experiments in knockout mice have greatly improved our understanding of hemidesmosomes and their associated structures in the cytoskeleton and basement membrane of the skin and mucous membranes. At leas

  12. Dosimetry for Total Skin Electron Beam Therapy in Skin Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Sung Sil; Loh, John J. K.; Kim, Gwi Eon [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1992-06-15

    Increasing frequency of skin cancer, mycosis fungoides, Kaposi sarcoma etc, it need to treatment dose planning for total skin electron beam (TSEB) therapy. Appropriate treatment planning for TSEB therapy is needed to give homogeneous dose distribution throughout the entire skin surface. The energy of 6 MeV electron from the 18 MeV medical linear accelerator was adapted for superficial total skin electron beam therapy. The energy of the electron beam was reduced to 4.2 MeV by a 0.5cmx90cmx180cm acryl screen placed in a feet front of the patient. Six dual field beam was adapted for total skin irradiation to encompass the entire body surface from head to toe simultaneously. The patients were treated behind the acryl screen plate acted as a beam scatterer and contained a parallel-plate shallow ion chamber for dosimetry and beam monitoring. During treatment, the patient was placed in six different positions due to be homogeneous dose distribution for whole skin around the body. One treatment session delivered 400 cGy to the entire skin surface and patients were treated twice a week for eight consecutive weeks, which is equivalent to TDF value 57. Instrumentation and techniques developed in determining the depth dose, dose distribution and bremsstrahlung dose are discussed.

  13. Skin protection in the prevention of skin diseases.

    Science.gov (United States)

    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.

  14. Expression of RANTES mRNA in skin lesions of feline eosinophilic plaque.

    Science.gov (United States)

    Kimura, Tomoe; Kano, Rui; Maeda, Sadatoshi; Tsujimoto, Hajime; Nagata, Masahiko; Hasegawa, Atsuhiko

    2003-10-01

    One of the mechanisms of eosinophil infiltration is its induction by chemoattractants such as regulated upon activation, normal T-expressed and secreted (RANTES) which is a cysteine-cysteine chemokine that mediates chemotaxis and activation of eosinophils in humans and mice. Skin lesions of feline eosinophilic plaque are characterized by a predominant infiltration of eosinophils. The mechanism(s) of eosinophilic infiltration in the skin and/or mucosa of cats is unknown. It is possible that RANTES is involved. To investigate the presence of RANTES in the skin of cats with eosinophilic plaques and nonaffected skin, we cloned and sequenced the full-length feline RANTES cDNA gene, in order to determine whether it is present in the skin of cats with eosinophilic plaques and/or if it is present in normal adjacent skin. We were able to document the the expression of RANTES mRNAs in skin with feline eosinophilic plaque as well as in normal cat skin. The full-length cDNA sequence of the RANTES gene (742 bp) contained a single open reading frame of 276 bp encoding a protein of 92 amino acids. The amino acid sequence of feline RANTES shared 67 and 74% sequence identity with that of bovine and mouse RANTES genes, respectively. RT-PCR analysis on RANTES mRNA in the skin of cats with eosinophilic plaque revealed that its expression was higher in the eosinophilic plaque skin lesions than in the normal skin. The result suggested that RANTES might play a role to induce eosinophil infiltration in feline eosinophilic plaque lesions.

  15. In situ depletion of CD4(+) T cells in human skin by Zanolimumab

    DEFF Research Database (Denmark)

    Villadsen, L.S.; Skov, L.; Dam, T.N.

    2007-01-01

    -driving T cells in situ may therefore be a useful approach in the treatment of inflammatory and malignant skin diseases. Depletion of CD4(+) T cells in intact inflamed human skin tissue by Zanolimumab, a fully human therapeutic monoclonal antibody (IgG1, kappa) against CD4, was studied in a human psoriasis......CD4(+) T cells, in activated or malignant form, are involved in a number of diseases including inflammatory skin diseases such as psoriasis, and T cell lymphomas such as the majority of cutaneous T cell lymphomas (CTCL). Targeting CD4 with an antibody that inhibits and/or eliminates disease...... xenograft mouse model. Zanolimumab treatment was shown to induce a significant reduction in the numbers of inflammatory mononuclear cells in upper dermis. This reduction in inflammatory mononuclear cells in situ was primarily due to a significant reduction in the numbers of skin-infiltrating CD4...

  16. Skin Exposures & Effects in the Workplace

    Science.gov (United States)

    ... Topics Publications and Products Programs Contact NIOSH NIOSH SKIN EXPOSURES & EFFECTS Recommend on Facebook Tweet Share Compartir ... currently lacking for measuring and assessing skin exposures. Skin Notation (SK) Profiles NIOSH has developed a strategy ...

  17. The Mouse SAGE Site: database of public mouse SAGE libraries.

    Science.gov (United States)

    Divina, Petr; Forejt, Jirí

    2004-01-01

    The Mouse SAGE Site is a web-based database of all available public libraries generated by the Serial Analysis of Gene Expression (SAGE) from various mouse tissues and cell lines. The database contains mouse SAGE libraries organized in a uniform way and provides web-based tools for browsing, comparing and searching SAGE data with reliable tag-to-gene identification. A modified approach based on the SAGEmap database is used for reliable tag identification. The Mouse SAGE Site is maintained on an ongoing basis at the Institute of Molecular Genetics, Academy of Sciences of the Czech Republic and is accessible at the internet address http://mouse.biomed.cas.cz/sage/.

  18. Mouse Leydig Tumor Cells

    Directory of Open Access Journals (Sweden)

    Bo-Syong Pan

    2011-01-01

    Full Text Available Cordycepin is a natural pure compound extracted from Cordyceps sinensis (CS. We have demonstrated that CS stimulates steroidogenesis in primary mouse Leydig cell and activates apoptosis in MA-10 mouse Leydig tumor cells. It is highly possible that cordycepin is the main component in CS modulating Leydig cell functions. Thus, our aim was to investigate the steroidogenic and apoptotic effects with potential mechanism of cordycepin on MA-10 mouse Leydig tumor cells. Results showed that cordycepin significantly stimulated progesterone production in dose- and time-dependent manners. Adenosine receptor (AR subtype agonists were further used to treat MA-10 cells, showing that A1, A 2A , A 2B , and A3, AR agonists could stimulate progesterone production. However, StAR promoter activity and protein expression remained of no difference among all cordycepin treatments, suggesting that cordycepin might activate AR, but not stimulated StAR protein to regulate MA-10 cell steroidogenesis. Meanwhile, cordycepin could also induce apoptotic cell death in MA-10 cells. Moreover, four AR subtype agonists induced cell death in a dose-dependent manner, and four AR subtype antagonists could all rescue cell death under cordycepin treatment in MA-10 cells. In conclusion, cordycepin could activate adenosine subtype receptors and simultaneously induce steroidogenesis and apoptosis in MA-10 mouse Leydig tumor cells.

  19. Colonization, mouse-style

    Directory of Open Access Journals (Sweden)

    Searle Jeremy B

    2010-10-01

    Full Text Available Abstract Several recent papers, including one in BMC Evolutionary Biology, examine the colonization history of house mice. As well as background for the analysis of mouse adaptation, such studies offer a perspective on the history of movements of the humans that accidentally transported the mice. See research article: http://www.biomedcentral.com/1471-2148/10/325

  20. Age-related skin changes

    Directory of Open Access Journals (Sweden)

    Božanić Snežana

    2012-01-01

    Full Text Available Age-related skin changes can be induced by chronological ageing, manifested in subcutaneous fat reduction, and photo-ageing eliciting increased elastotic substance in the upper dermis, destruction of its fibrilar structure, augmented intercellular substance and moderate inflammatory infiltrate. Forty-five biopsy skin samples of the sun-exposed and sun-protected skin were analyzed. The patients were both males and females, aged from 17 to 81 years. The thickness of the epidermal layers and the number of cellular living layers is greater in younger skin. The amount of keratohyaline granules is enlarged in older skin. Dermoepidermal junction is flattened and the presence of elastotic material in the dermis is pronounced with age. The amount of inflammatory infiltrate is increased, the fibrous trabeculae are thickened in older skin and the atrophy of the hypodermis is observed. Chronological ageing alters the fibroblasts metabolism by reducing their life span, capacity to divide and produce collagen. During ageing, the enlargement of collagen fibrils diminishes the skin elasticity.

  1. Biothermomechanical behavior of skin tissue

    Institute of Scientific and Technical Information of China (English)

    F.Xu; T.J.Lu; K.A.Seffen

    2008-01-01

    Advances in laser,microwave and similar tech nologies have led to recent developments of thermal treatments involving skin tissue.The effectiveness of these treatments is governed by the coupled thermal,mechanical,biological and neural responses of the affected tissue:a favorable interaction results in a procedure with relatively little pain and no lasting side effects.Currently,even though each behavioral facet is to a certain extent established and understood,none exists to date in the interdisciplinarv area.A highly interdisciplinary approach is required for studying the biothermomechanical behavior of skin,involving bioheat transfer.biomechanics and physiology.A comprehensive literature review penrtinent to the subject is presented in this paper,covering four subject areas:(a)skin structure,(b)skin bioheat transfer and thermal damage,(c)skin biomechanics,and(d)skin biothermomechanics.The major problems,issues,and topics for further studies are also outlined.This review finds that significant advances in each of these aspects have been achieved in recent years.Although focus is placed upon the biothermomechanical behavior of skin tissue,the fundamental concepts and methodologies reviewed in this paper may also be applicable for studying other soft tissues.

  2. Human skin volatiles: a review.

    Science.gov (United States)

    Dormont, Laurent; Bessière, Jean-Marie; Cohuet, Anna

    2013-05-01

    Odors emitted by human skin are of great interest to biologists in many fields; applications range from forensic studies to diagnostic tools, the design of perfumes and deodorants, and the ecology of blood-sucking insect vectors of human disease. Numerous studies have investigated the chemical composition of skin odors, and various sampling methods have been used for this purpose. The literature shows that the chemical profile of skin volatiles varies greatly among studies, and the use of different sampling procedures is probably responsible for some of these variations. To our knowledge, this is the first review focused on human skin volatile compounds. We detail the different sampling techniques, each with its own set of advantages and disadvantages, which have been used for the collection of skin odors from different parts of the human body. We present the main skin volatile compounds found in these studies, with particular emphasis on the most frequently studied body regions, axillae, hands, and feet. We propose future directions for promising experimental studies on odors from human skin, particularly in relation to the chemical ecology of blood-sucking insects.

  3. Phantom and mouse experiments of time-domain fluorescence tomography using total light approach.

    Science.gov (United States)

    Okawa, Shinpei; Yano, Akira; Uchida, Kazuki; Mitsui, Yohei; Yoshida, Masaki; Takekoshi, Masashi; Marjono, Andhi; Gao, Feng; Hoshi, Yoko; Kida, Ikuhiro; Masamoto, Kazuto; Yamada, Yukio

    2013-04-01

    Phantom and mouse experiments of time-domain fluorescence tomography were conducted to demonstrate the total light approach which was previously proposed by authors. The total light approach reduces the computation time to solve the forward model for light propagation. Time-resolved temporal profiles were acquired for cylindrical phantoms having single or double targets containing indocyanine green (ICG) solutions. The reconstructed images of ICG concentration reflected the true distributions of ICG concentration with a spatial resolution of about 10 mm. In vivo experiments were conducted using a mouse in which an ICG capsule was embedded beneath the skin in the abdomen. The reconstructed image of the ICG concentration again reflected the true distribution of ICG although artifacts due to autofluorescence appeared in the vicinity of the skin. The effectiveness of the total light approach was demonstrated by the phantom and mouse experiments.

  4. Use of PC mouse components for continuous measuring of human heartbeat.

    Science.gov (United States)

    Beiderman, Yevgeny; Talyosef, Roy; Yeori, Daniel; Garcia, Javier; Mico, Vicente; Zalevsky, Zeev

    2012-06-01

    A new technology for remote measuring of vibration sources was recently developed for industrial, medical, and security-related applications [Int. Appl. Patent No: PCT/IL2008/001008]. It requires relatively expensive equipment, such as high-speed complementary metal oxide semiconductor (CMOS) sensors and customized optics. In this paper, we demonstrate how the usage of a simple personal computer (PC) mouse as an optical system composed of a low-power laser and a CMOS circuitry on the same integrated circuit package, can be used to monitor heartbeat from the wrist. The method is based on modifying the mouse optical system in such a way that it will recognize temporal change in skin's vibration profile, generated due to the heart pulses, as mouse movement. The tests that were carried out show a very good correlation between the heartbeat rate measured from human skin and the reference values taken manually.

  5. Filaggrin and Skin Barrier Function.

    Science.gov (United States)

    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

  6. Chemokines in the skin

    Directory of Open Access Journals (Sweden)

    Prasad D

    1998-01-01

    Full Text Available In last few years, focus has shifted from cytokines which have pleiotropic biologic properties to chemokines with target cell selective activity. The separation has led frequently espoused proposition that chemokines are involved in the pathogenesis of disease having specific infiltrates and point to possible role in Chronic skin diseases. Depending upon the structure these chemokines are divided into three subfamilies, two major subfamilies: CXC and CC, and one putative subfamily C with only one member known as lymphotactin. A recent insight into chemokine physiology comes from demonstration of interaction between chemokines and their cloned receptors. These chemokine receptors are members of the transmembrane spanning (7-TMS, G-protein- coupled receptor family. So far CXC chemokine receptors and seven CC receptors have been cloned. Recently, the importance of selective chemoattractant activity of chemokines has been overshadowed by chemokine receptors emerging as new targets for anti-HIV therapy as the connection between chemokines and HIV-I had been established. Among the CXC chemokine receptors, CXCR4, and among the CC chemokines receptors, CCRI, CCR2b, CCR3, and CCR5 have been implicated as HIV-1 coreceptors.

  7. Development of prosthetic skin

    Science.gov (United States)

    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.

  8. Revertant mosaicism in the skin.

    Science.gov (United States)

    Lai-Cheong, J E; McGrath, J A

    2013-02-01

    Revertant mosaicism is a naturally occurring phenomenon involving the spontaneous correction of a pathogenic mutation in a somatic cell. Revertant mosaicism is not a rare event and has been described in several inherited skin conditions, including various subtypes of epidermolysis bullosa. The recognition of revertant mosaicism paves the way for revertant therapy which represents a potentially exciting "natural gene therapy" option for genetic disorders. The skin provides a useful model for studying revertant mosaicism because it is readily accessible and easy to examine. In this paper, we provide an overview of revertant mosaicism and its relevance in genetic skin disorders.

  9. Skin-inspired electronic devices

    Directory of Open Access Journals (Sweden)

    Alex Chortos

    2014-09-01

    Full Text Available Electronic devices that mimic the properties of skin have potential important applications in advanced robotics, prosthetics, and health monitoring technologies. Methods for measuring tactile and temperature signals have progressed rapidly due to innovations in materials and processing methods. Imparting skin-like stretchability to electronic devices can be accomplished by patterning traditional electronic materials or developing new materials that are intrinsically stretchable. The incorporation of sensing methods with transistors facilitates large-area sensor arrays. While sensor arrays have surpassed the properties of human skin in terms of sensitivity, time response, and device density, many opportunities remain for future development.

  10. Sulfate transport in toad skin

    DEFF Research Database (Denmark)

    Larsen, Erik Hviid; Simonsen, K

    1988-01-01

    1. In short-circuited toad skin preparations exposed bilaterally to NaCl-Ringer's containing 1 mM SO2(-4), influx of sulfate was larger than efflux showing that the skin is capable of transporting sulfate actively in an inward direction. 2. This active transport was not abolished by substituting...... apical Na+ for K+. 3. Following voltage activation of the passive Cl- permeability of the mitochondria-rich (m.r.) cells sulfate flux-ratio increased to a value predicted from the Ussing flux-ratio equation for a monovalent anion. 4. In such skins, which were shown to exhibit vanishingly small leakage...

  11. [Non-irritating skin protector].

    Science.gov (United States)

    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.

  12. Skin Treatments and Dermatological Procedures to Promote Youthful Skin

    OpenAIRE

    Sator, Paul G

    2006-01-01

    The skin, the largest organ of the body, is the organ in which changes associated with aging are most visible. With increasing frequency, patients are requesting information and treatments that improve the appearance of their skin. Corresponding to this trend, there is an increasing number of products and methods available that claim to aid this pursuit. First, a change of the patient's lifestyle (eg, sun behavior, nicotine abuse, and nutrition) must take place. Only then may other methods be...

  13. Skin temperature during sunbathing--relevance for skin cancer.

    Science.gov (United States)

    Petersen, Bibi; Philipsen, Peter Alshede; Wulf, Hans Christian

    2014-08-01

    It has been found that exposure to heat and infrared radiation (IR) can be carcinogenic, and that a combination of ultraviolet radiation (UVR) and IR possibly amplifies carcinogenesis. To investigate how the skin temperature is affected by sunbathing, we measured the skin temperature on 20 healthy volunteers over 6 days' sun holiday in Egypt. Temperatures were measured with an infrared thermometer gun at 8 skin sites on the volunteers while they were indoors in the morning and when sunbathing during the day. Skin temperatures were higher during sunbathing (33.5 °C ± 2.1 °C) (mean ± SD) than when indoors in the morning (32.6 °C ± 1.4 °C) (mean ± SD) (P < 0.0001). The average skin temperature for men was higher than for women by 0.40 °C in the morning (P = 0.02) and by 0.44 °C during sunbathing (P < 0.0001). Our results show that sunbathing has an impact on skin temperature, which possibly by activation of the heat shock response, is likely to contribute to the immediate and delayed effects of UV in a way that has to be found out in future studies.

  14. Skin temperature during sunbathing--relevance for skin cancer

    DEFF Research Database (Denmark)

    Petersen, Bibi; Philipsen, Peter Alshede; Wulf, Hans Christian

    2014-01-01

    It has been found that exposure to heat and infrared radiation (IR) can be carcinogenic, and that a combination of ultraviolet radiation (UVR) and IR possibly amplifies carcinogenesis. To investigate how the skin temperature is affected by sunbathing, we measured the skin temperature on 20 healthy...... volunteers over 6 days' sun holiday in Egypt. Temperatures were measured with an infrared thermometer gun at 8 skin sites on the volunteers while they were indoors in the morning and when sunbathing during the day. Skin temperatures were higher during sunbathing (33.5 °C ± 2.1 °C) (mean ± SD) than when...... indoors in the morning (32.6 °C ± 1.4 °C) (mean ± SD) (P skin temperature for men was higher than for women by 0.40 °C in the morning (P = 0.02) and by 0.44 °C during sunbathing (P skin temperature, which possibly...

  15. Skin microbiome and skin disease: the example of rosacea.

    Science.gov (United States)

    Picardo, Mauro; Ottaviani, Monica

    2014-01-01

    The imbalance and/or the perturbation of the microbial populations that colonize the skin and that contribute to its defense may represent one of the causes of the development of noninfectious skin diseases. Atopic dermatitis, psoriasis, acne, and rosacea can be listed among these kinds of pathologies. In particular, considering that microbes have been long addressed as having a role in rosacea, this common dermatosis can be an interesting model to evaluate the correlation between microbiome alterations and the occurrence of clinical manifestations. Different microorganisms have been suggested to have a role in rosacea, but no direct correlation with the incidence of the pathology has been clearly defined. Skin microbiome composition is crucial for the correct skin immune functions and recent findings indicate an abnormal activation of innate immune system associated with the rosacea. The enhanced expression of toll-like receptor 2 in the epidermis of rosacea patients can represent a possible explanation for the amplified inflammatory response to external stimuli observed during the disease. In addition, significantly higher small intestinal bacterial overgrowth prevalence in rosacea subjects has been found and its eradication has been associated with a regression of the skin lesions. In conclusion, both skin and gut microbiome seem to have a role, even if synergistic with other factors, in the pathogenesis of rosacea. A deeper knowledge of human microbiome composition and microbe-host interactions will contribute to clarify the mechanism of development of rosacea and possibly will provide innovative therapeutic approaches.

  16. Kaempferol targets RSK2 and MSK1 to suppress UV radiation-induced skin cancer.

    Science.gov (United States)

    Yao, Ke; Chen, Hanyong; Liu, Kangdong; Langfald, Alyssa; Yang, Ge; Zhang, Yi; Yu, Dong Hoon; Kim, Myoung Ok; Lee, Mee-Hyun; Li, Haitao; Bae, Ki Beom; Kim, Hong-Gyum; Ma, Wei-Ya; Bode, Ann M; Dong, Ziming; Dong, Zigang

    2014-09-01

    Solar UV (SUV) irradiation is a major factor in skin carcinogenesis, the most common form of cancer in the United States. The MAPK cascades are activated by SUV irradiation. The 90 kDa ribosomal S6 kinase (RSK) and mitogen and stress-activated protein kinase (MSK) proteins constitute a family of protein kinases that mediate signal transduction downstream of the MAPK cascades. In this study, phosphorylation of RSK and MSK1 was upregulated in human squamous cell carcinoma (SCC) and SUV-treated mouse skin. Kaempferol, a natural flavonol, found in tea, broccoli, grapes, apples, and other plant sources, is known to have anticancer activity, but its mechanisms and direct target(s) in cancer chemoprevention are unclear. Kinase array results revealed that kaempferol inhibited RSK2 and MSK1. Pull-down assay results, ATP competition, and in vitro kinase assay data revealed that kaempferol interacts with RSK2 and MSK1 at the ATP-binding pocket and inhibits their respective kinase activities. Mechanistic investigations showed that kaempferol suppresses RSK2 and MSK1 kinase activities to attenuate SUV-induced phosphorylation of cAMP-responsive element binding protein (CREB) and histone H3 in mouse skin cells. Kaempferol was a potent inhibitor of SUV-induced mouse skin carcinogenesis. Further analysis showed that skin from the kaempferol-treated group exhibited a substantial reduction in SUV-induced phosphorylation of CREB, c-Fos, and histone H3. Overall, our results identify kaempferol as a safe and novel chemopreventive agent against SUV-induced skin carcinogenesis that acts by targeting RSK2 and MSK1.

  17. Cyclophosphamide (CYP) Inhibition on the Growth of Skin Through the Activation of Caspase-1 in Mouse%环磷酰胺(CYP)通过激活Caspase-1诱导表达抑制小鼠皮肤的生长

    Institute of Scientific and Technical Information of China (English)

    向志雄; 付鹏; 齐麟; 贺洪

    2012-01-01

    Cyclophosphamide is a chemotherapy drug widey used in endometrial cancer, B-type lymphoma, central nervous system neoplasm, etc. However, one of the serious side effects of cyclophosphamide is its skin toxicity, and the underlying molecular mechanism is currently unclear. Cyclophosphamide induced caspase-1 expression, which mediates abnormal apoptosis and skin toxicity according to HE staining and Realtime qPCR experiment.%环磷酰胺对于子宫内膜癌、B细胞淋巴癌、中央神经系统肿瘤等各类癌症的治疗有着良好的效果.但是,一个重要的问题是它对于患者的皮肤,产生严重的有害作用,产生这个作用的详细机制还不是很清楚.苏木精-伊红(hematoxylin-eosin,HE)染色和实时荧光定量PCR (Real-time qPCR)实验结果表明,环磷酰胺诱导caspase-1过量表达,而caspase-1基因的诱导性表达,可能引起了皮肤的非正常凋亡,从而对皮肤构成毒害.

  18. Periodic control of rate of drug permeation through the skin with iontophoresis

    Energy Technology Data Exchange (ETDEWEB)

    Yamashita, A.; Tanaka, K.; Tojo, K. [Kyushu Institute of Technology, Fukuoka (Japan)

    1996-10-20

    Iontophoresis, which enhances the rate of charged drugs through a membrane by applying an electric current, is a novel promising technique for a drug delivery system. The authors used iontophoresis to enhance the skin permeability of drugs in transdermal delivery. In vitro permeation experiments across a piece of excised hairless mouse skin were made with/without electric field application. A model drug, benzoic acid (BA, MW=122), did not passively penetrate through the intact hairless mouse skin at pH=7.4 (almost completely ignited); however, it could appreciably permeate through the skin when an electric current density of 3.0 A/m{sup 2} was applied. The permeation flux of BA through the skin was linearly changed with the electric current density, which makes it possible to control drug concentration in the blood periodically. The permeation flux of dexamethasone sodium m-sulfobenzoate (MW=599), which is larger than BA, was also enhanced by applying iontophoresis. Computer simulation was performed for iontophoresis experiments using transport parameters determined from passive diffusion experiments. Experimental findings under iontophoresis were well correlated by the results of computer simulation, which may be useful for designing an optimal administrating schedule for a specific drug. 6 refs., 11 figs., 1 tab.

  19. Variations in the optical scattering properties of skin in murine animal models

    Science.gov (United States)

    Calabro, Katherine; Curtis, Allison; Galarneau, Jean-Rene; Krucker, Thomas; Bigio, Irving J.

    2011-03-01

    In the work presented here, the optical scattering properties of mouse skin are investigated in depth with the use of Elastic Scattering Spectroscopy (ESS). In particular, sources of variation that lead to experimental error are identified and examined. The thickness of the dermal layer of the skin is determined to be the primary source of variation due to its high collagen content. Specifically, gender differences in skin thickness are found to cause increases in the reflectance and scattering coefficient value by a factor of two in males as opposed to females. Changes in the hair growth cycle are found to influence scattering strength not only due to changes in skin thickness, but also from melanin collection in hair follicles. Because direct and/or indirect measurement of mouse skin is common in the development of novel biomedical optics techniques (optical biopsy, molecular imaging, in vivo monitoring of glucose/blood oxygenation, etc.), the purpose of this work is to identify sources of experimental variation that may arise in these studies such that care can be taken to avoid or compensate for their affects.

  20. Significant determinants of mouse pain behaviour.

    Directory of Open Access Journals (Sweden)

    Michael S Minett

    Full Text Available Transgenic mouse behavioural analysis has furthered our understanding of the molecular and cellular mechanisms underlying damage sensing and pain. However, it is not unusual for conflicting data on the pain phenotypes of knockout mice to be generated by reputable groups. Here we focus on some technical aspects of measuring mouse pain behaviour that are often overlooked, which may help explain discrepancies in the pain literature. We examined touch perception using von Frey hairs and mechanical pain thresholds using the Randall-Selitto test. Thermal pain thresholds were measured using the Hargreaves apparatus and a thermal place preference test. Sodium channel Nav1.7 knockout mice show a mechanical deficit in the hairy skin, but not the paw, whilst shaving the abdominal hair abolished this phenotype. Nav1.7, Nav1.8 and Nav1.9 knockout mice show deficits in noxious mechanosensation in the tail, but not the paw. TRPA1 knockout mice, however, have a loss of noxious mechanosensation in the paw but not the tail. Studies of heat and cold sensitivity also show variability depending on the intensity of the stimulus. Deleting Nav1.7, Nav1.8 or Nav1.9 in Nav1.8-positive sensory neurons attenuates responses to slow noxious heat ramps, whilst responses to fast noxious heat ramps are only reduced when Nav1.7 is lost in large diameter sensory neurons. Deleting Nav1.7 from all sensory neurons attenuates responses to noxious cooling but not extreme cold. Finally, circadian rhythms dramatically influence behavioural outcome measures such as von Frey responses, which change by 80% over the day. These observations demonstrate that fully characterising the phenotype of a transgenic mouse strain requires a range of behavioural pain models. Failure to conduct behavioural tests at different anatomical locations, stimulus intensities, and at different points in the circadian cycle may lead to a pain behavioural phenotype being misinterpreted, or missed altogether.

  1. The skin-blanching assay.

    Science.gov (United States)

    Smit, P; Neumann, H A M; Thio, H B

    2012-10-01

    The skin-blanching assay is used for the determination and bioequivalence of dermatologic glucocorticoids (GCs). The exact mechanism of the production of blanching is not fully understood, but it is considered that local vasoconstriction of the skin microvasculature and the consequent blood-flow reduction cause this phenomenon. Several factors influence skin blanching, including drug concentration, duration of application, nature of vehicle, occlusion, posture and location. The intensity of vasoconstriction can be measured in several ways: visual or quantitative methods, such as reflectance spectroscopy, thermography, laser Doppler velocimetry and chromametry. In literature, contradicting results in the correlation of the skin-blanching assay with different tests to determine GC sensitivity have been reported, limiting its clinical usefulness.

  2. Dry skin - self-care

    Science.gov (United States)

    ... moisture Hot, dry air in desert environments Air conditioners that cool the air and remove moisture Taking ... scrubbing your skin. Shave right after bathing, when hair is soft. Wear soft, comfortable clothing next to ...

  3. Drugs Approved for Skin Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for skin cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  4. [Vitamin D and the skin].

    Science.gov (United States)

    Libon, F; Cavalier, E; Nikkels, A F

    2013-09-01

    Vitamin D is well known for its beneficial effects on phosphocalcic homeostasis. The discovery of the role of vitamin D in cancers, infections, cardiovascular or autoimmune pathologies have promoted interest for this molecule. Skin and vitamin D are closely related. The skin is not only the site of vitamin D synthesis, but also a target organ as calcitriol plays an important hormonal and regulatory role, acting on cell proliferation, differentiation and immunomodulation. Furthermore, vitamin D influences the incidence and therapeutic response of certain dermatoses. In addition, many medical situations, mainly dermatological, require strict photoprotection and may therefore indirectly be responsible for a vitamin D deficiency in patients. The current role of vitamin D in skin cancers, inflammatory and autoimmune skin diseases is summarized.

  5. Radiation Therapy for Skin Cancer

    Science.gov (United States)

    ... make sure they are safe to use during radiation therapy. • Eat a balanced diet. If food tastes ... your fluid intake. • Treat the skin exposed to radiation with special care. Stay out of the sun, ...

  6. Skin Barrier Function and Allergens

    DEFF Research Database (Denmark)

    Engebretsen, Kristiane Aasen; Thyssen, Jacob Pontoppidan

    2016-01-01

    The skin is an important barrier protecting us from mechanical insults, microorganisms, chemicals and allergens, but, importantly, also reducing water loss. A common hallmark for many dermatoses is a compromised skin barrier function, and one could suspect an elevated risk of contact sensitization...... and skin barrier status. Psoriasis has traditionally been regarded a Th1-dominated disease, but the discovery of Th17 cells and IL-17 provides new and interesting information regarding the pathogenesis of the disease. Research suggests an inverse relationship between psoriasis and CA, possibly due......) and Th2 (AD) have been proposed as an explanation. Finally, there is convincing evidence that exposure to irritants increases the risk of CS, and patients with ICD are, therefore, at great risk of developing CA. Skin irritation leads to the release of IL-1 and TNF-α, which affects the function of antigen...

  7. Vitamin D and skin cancer.

    Science.gov (United States)

    Burns, Erin M; Elmets, Craig A; Yusuf, Nabiha

    2015-01-01

    Vitamin D signaling plays a key role in many important processes, including cellular proliferation, differentiation and apoptosis, immune regulation, hormone secretion and skeletal health. Furthermore, vitamin D production and supplementation have been shown to exert protective effects via an unknown signaling mechanism involving the vitamin D receptor (VDR) in several diseases and cancer types, including skin cancer. With over 3.5 million new diagnoses in 2 million patients annually, skin cancer is the most common cancer type in the United States. While ultraviolet B (UVB) radiation is the main etiologic factor for nonmelanoma skin cancer (NMSC), UVB also induces cutaneous vitamin D production. This paradox has been the subject of contradictory findings in the literature in regards to amount of sun exposure necessary for appropriate vitamin D production, as well as any beneficial or detrimental effects of vitamin D supplementation for disease prevention. Further clinical and epidemiological studies are necessary to elucidate the role of vitamin D in skin carcinogenesis.

  8. Moisturizers: Options for Softer Skin

    Science.gov (United States)

    ... producing glands become less active. To keep your skin soft and well-hydrated, choose an oil-based moisturizer that contains petrolatum as the base, along with antioxidants or alpha hydroxy acids to combat wrinkles. These ...

  9. Discovery – Preventing Skin Cancer

    Science.gov (United States)

    Cancer research includes stopping cancer before it spreads. NCI funded the development of the Melanoma Risk Assessment Tool and the ABC method. Both help to diagnose high-risk patients and prevent melanoma earlier in the fight against skin cancer.

  10. Loss of ceramide synthase 3 causes lethal skin barrier disruption.

    Science.gov (United States)

    Jennemann, Richard; Rabionet, Mariona; Gorgas, Karin; Epstein, Sharon; Dalpke, Alexander; Rothermel, Ulrike; Bayerle, Aline; van der Hoeven, Franciscus; Imgrund, Silke; Kirsch, Joachim; Nickel, Walter; Willecke, Klaus; Riezman, Howard; Gröne, Hermann-Josef; Sandhoff, Roger

    2012-02-01

    The stratum corneum as the outermost epidermal layer protects against exsiccation and infection. Both the underlying cornified envelope (CE) and the intercellular lipid matrix contribute essentially to these two main protective barriers. Epidermis-unique ceramides with ultra-long-chain acyl moities (ULC-Cers) are key components of extracellular lipid lamellae (ELL) and are bound to CE proteins, thereby contributing to the cornified lipid envelope (CLE). Here, we identified human and mouse ceramide synthase 3 (CerS3), among CerS1-6, to be exclusively required for the ULC-Cer synthesis in vitro and of mouse CerS3 in vivo. Deficiency of CerS3 in mice results in complete loss of ULC-Cers (≥C26), lack of continuous ELL and a non-functional CLE. Consequently, newborn mutant mice die shortly after birth from transepidermal water loss. Mutant skin is prone to Candida albicans infection highlighting ULC-Cers to be pivotal for both barrier functions. Persistent periderm, hyperkeratosis and deficient cornification are hallmarks of mutant skin demonstrating loss of Cers to trigger a keratinocyte maturation arrest at an embryonic pre-barrier stage.

  11. Update on the validation and regulatory acceptance of alternative tests for skin corrosion and irritation.

    Science.gov (United States)

    Fentem, Julia H; Botham, Philip A

    2004-06-01

    The European Centre for the Validation of Alternative Methods (ECVAM) has supported validation studies on in vitro tests for skin corrosion, resulting in the validities of four alternative tests being endorsed. The US Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) has also evaluated the validity of these alternative methods for skin corrosion testing. In the European Union, a new Test Method on Skin Corrosion (B.40), incorporating the rat skin transcutaneous electrical resistance and human skin model assays, was included in Annex V of Directive 67/548/EEC in mid-2000. At an international level, two OECD Test Guidelines (430 and 431) on these alternative methods have been approved as of May 2002. To date, there are no validated in vitro tests for predicting the dermal irritancy of chemicals. ECVAM supported prevalidation studies on five in vitro tests for acute skin irritation during 1999-2001. These tests were based on human, pig and mouse skin. However, none of them met the criteria set for inclusion in a large-scale formal validation study. Following additional work on the test protocols and/or prediction models, it appears that several modified tests could now be ready for validation in 2003.

  12. Dexamethasone prevents granulocyte-macrophage colony-stimulating factor-induced nuclear factor-κB activation, inducible nitric oxide synthase expression and nitric oxide production in a skin dendritic cell line

    Directory of Open Access Journals (Sweden)

    Ana Luísa Vital

    2003-01-01

    Full Text Available Aims: Nitric oxide (NO has been increasingly implicated in inflammatory skin diseases, namely in allergic contact dermatitis. In this work, we investigated the effect of dexamethasone on NO production induced by the epidermal cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF in a mouse fetal skin dendritic cell line.

  13. Anti-melasma codrug of retinoic acid assists cutaneous absorption with attenuated skin irritation.

    Science.gov (United States)

    Hsieh, Pei-Wen; Hung, Chi-Feng; Lin, Chih-Hung; Huang, Chang-Wei; Fang, Jia-You

    2017-05-01

    Melasma treatment with combined retinoic acid (RA) and hydroquinone (HQ) usually causes unsatisfactory outcomes and safety concerns. This study attempted to evaluate the cutaneous absorption and skin tolerance of the codrug conjugated with RA and HQ via ester linkage. The codrug's permeation of the pig skin was estimated using Franz diffusion cell. The codrug and parent drugs were comparatively examined for anti-inflammatory activity and tyrosinase inhibition. In vivo cutaneous irritation was assessed on nude mouse skin. Chemical conjugation of RA with HQ increased the lipophilicity and thus the skin absorption. The codrug absorption produced a 5.5- and a 60.8-fold increment compared to RA skin deposition at an equimolar (1.2mM) and saturated solubility dose, respectively. The cumulative amount of HQ derived from the codrug in the receptor was comparable to or less than that of topically applied HQ. The RA-HQ codrug was partly hydrolyzed on penetrating the skin. The hydrolysis rate in intact skin was significantly lower than that in esterase medium and skin homogenates. The codrug showed an interleukin (IL)-6 inhibition activity comparable to RA. A therapeutic index 6-fold greater than RA was obtained with the topical codrug. The tyrosinase inhibition percentage of the codrug and HQ was 13% and 21%, respectively. The skin tolerance test determined by transepidermal water loss (TEWL), redness, and histopathology had exhibited minor skin irritation caused by the codrug compared to the physical mixture of RA and HQ at an equivalent dose. Topical codrug delivery not only promoted RA absorption, but also diminished the adverse effects of the parent agents.

  14. Sexual hormones in human skin.

    Science.gov (United States)

    Zouboulis, C C; Chen, W-C; Thornton, M J; Qin, K; Rosenfield, R

    2007-02-01

    The skin locally synthesizes significant amounts of sexual hormones with intracrine or paracrine actions. The local level of each sexual steroid depends upon the expression of each of the androgen- and estrogen-synthesizing enzymes in each cell type, with sebaceous glands and sweat glands being the major contributors. Sebocytes express very little of the key enzyme, cytochrome P450c17, necessary for synthesis of the androgenic prohormones dehydroepiandrosterone and androstenedione, however, these prohormones can be converted by sebocytes and sweat glands, and probably also by dermal papilla cells, into more potent androgens like testosterone and dihydrotestosterone. Five major enzymes are involved in the activation and deactivation of androgens in skin. Androgens affect several functions of human skin, such as sebaceous gland growth and differentiation, hair growth, epidermal barrier homeostasis and wound healing. Their effects are mediated by binding to the nuclear androgen receptor. Changes of isoenzyme and/or androgen receptor levels may have important implications in the development of hyperandrogenism and the associated skin diseases such as acne, seborrhoea, hirsutism and androgenetic alopecia. On the other hand, estrogens have been implicated in skin aging, pigmentation, hair growth, sebum production and skin cancer. Estrogens exert their actions through intracellular receptors or via cell surface receptors, which activate specific second messenger signaling pathways. Recent studies suggest specific site-related distribution of ERalpha and ERbeta in human skin. In contrast, progestins play no role in the pathogenesis of skin disorders. However, they play a major role in the treatment of hirsutism and acne vulgaris, where they are prescribed as components of estrogen-progestin combination pills and as anti-androgens. These combinations enhance gonadotropin suppression of ovarian androgen production. Estrogen-progestin treatment can reduce the need for shaving

  15. N-Nicotinoyl dopamine inhibits skin pigmentation by suppressing of melanosome transfer.

    Science.gov (United States)

    Kim, Bora; Hwang, Jae Sung; Kim, Hyun-Soo

    2015-12-15

    We investigated the inhibitory effects of a niacinamide derivative, N-Nicotinoyl dopamine (NND) on melanogenesis. NND inhibits melanosome transfer in a normal human melanocyte-keratinocyte co-culture system and through phagocytic ability without affecting viability of cells while it did not show inhibitory effects of tyrosinase and melanin synthesis in B16F10 mouse melanoma cells. In addition, safety of NND was verified through performing neural stem cell morphology assay. Our findings indicate that NND may potentially be used for cosmetic industry for improvement of skin whitening and therapies related with several skin disorders, and the effect of NND may be acquired via reduction of melanosome transfer.

  16. 19 CFR 12.63 - Seal-skin or sea-otter-skin waste.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Seal-skin or sea-otter-skin waste. 12.63 Section... OF THE TREASURY SPECIAL CLASSES OF MERCHANDISE Fur-Seal Or Sea-Otter Skins § 12.63 Seal-skin or sea-otter-skin waste. Seal-skin or sea-otter-skin waste composed of small pieces not large enough to...

  17. [New views about the skin].

    Science.gov (United States)

    Guimberteau, J-C; Delage, J-P; Wong, J

    2010-08-01

    As the follow up article to "Introduction to the knowledge of subcutaneous sliding system in humans" published in the "Annales de chirurgie plastique" we further investigate the architecture of the skin and comment on the subcutaneous multifibrillar and microvacuolar arrangements that provide form, mobility, adaptability and resistance to force of gravity. The study aimed to highlight the direct link between the skin and subcutaneous environment in dynamic living tissue. Through high resolution endoscopic observations made during live surgery it is revealed how microvacuoles and microspaces can provide dynamic structure and form during movement between the epidermis, dermis and hypodermis. The study reveals intriguing morphodynamics which are necessary to maintain mobility and continuity to neighboring tissues. The polyhedric design of the skin surface directly relates to multifibrillar pillars beneath the skin which dictate their patterning and movement. The concept of tissue continuity is realised by the chaotic and fractal organisation of multifibrils interlaced with cellular components which characteristics alter depending on the state of hydration. Understanding the integral arrangement that provides continuity of all the structures below the skin provides an appreciation to how skin behaves in relation to movement of the rest of the body.

  18. Pickering emulsions for skin decontamination.

    Science.gov (United States)

    Salerno, Alicia; Bolzinger, Marie-Alexandrine; Rolland, Pauline; Chevalier, Yves; Josse, Denis; Briançon, Stéphanie

    2016-08-01

    This study aimed at developing innovative systems for skin decontamination. Pickering emulsions, i.e. solid-stabilized emulsions, containing silica (S-PE) or Fuller's earth (FE-PE) were formulated. Their efficiency for skin decontamination was evaluated, in vitro, 45min after an exposure to VX, one of the most highly toxic chemical warfare agents. Pickering emulsions were compared to FE (FE-W) and silica (S-W) aqueous suspensions. PE containing an oil with a similar hydrophobicity to VX should promote its extraction. All the formulations reduced significantly the amount of VX quantified on and into the skin compared to the control. Wiping the skin surface with a pad already allowed removing more than half of VX. FE-W was the less efficient (85% of VX removed). The other formulations (FE-PE, S-PE and S-W) resulted in more than 90% of the quantity of VX removed. The charge of particles was the most influential factor. The low pH of formulations containing silica favored electrostatic interactions of VX with particles explaining the better elimination from the skin surface. Formulations containing FE had basic pH, and weak interactions with VX did not improve the skin decontamination. However, these low interactions between VX and FE promote the transfer of VX into the oil droplets in the FE-PE.

  19. Radiation sterilization of skin allograft

    Science.gov (United States)

    Kairiyama, E.; Horak, C.; Spinosa, M.; Pachado, J.; Schwint, O.

    2009-07-01

    In the treatment of burns or accidental loss of skin, cadaveric skin allografts provide an alternative to temporarily cover a wounded area. The skin bank facility is indispensable for burn care. The first human skin bank was established in Argentina in 1989; later, 3 more banks were established. A careful donor selection is carried out according to the national regulation in order to prevent transmissible diseases. As cadaveric human skin is naturally highly contaminated, a final sterilization is necessary to reach a sterility assurance level (SAL) of 10 -6. The sterilization dose for 106 batches of processed human skin was determined on the basis of the Code of Practice for the Radiation Sterilization of Tissue Allografts: Requirements for Validation and Routine Control (2004) and ISO 11137-2 (2006). They ranged from 17.6 to 33.4 kGy for bioburdens of >10-162.700 CFU/100 cm 2. The presence of Gram negative bacteria was checked for each produced batch. From the analysis of the experimental results, it was observed that the bioburden range was very wide and consequently the estimated sterilization doses too. If this is the case, the determination of a tissue-specific dose per production batch is necessary to achieve a specified requirement of SAL. Otherwise if the dose of 25 kGy is preselected, a standardized method for substantiation of this dose should be done to confirm the radiation sterilization process.

  20. Systemic antioxidants and skin health.

    Science.gov (United States)

    Nguyen, Gloria; Torres, Abel

    2012-09-01

    Most dermatologists agree that antioxidants help fight free radical damage and can help maintain healthy skin. They do so by affecting intracellular signaling pathways involved in skin damage and protecting against photodamage, as well as preventing wrinkles and inflammation. In today's modern world of the rising nutraceutical industry, many people, in addition to applying topical skin care products, turn to supplementation of the nutrients missing in their diets by taking multivitamins or isolated, man-made nutraceuticals, in what is known as the Inside-Out approach to skin care. However, ingestion of large quantities of isolated, fragmented nutrients can be harmful and is a poor representation of the kind of nutrition that can be obtained from whole food sources. In this comprehensive review, it was found that few studies on oral antioxidants benefiting the skin have been done using whole foods, and that the vast majority of current research is focused on the study of compounds in isolation. However, the public stands to benefit greatly if more research were to be devoted toward the impact that physiologic doses of antioxidants (obtained from fruits, vegetables, and whole grains) can have on skin health, and on health in general.

  1. Skin penetration and metabolism of topically applied chemicals in six mammalian species, including man: an in vitro study with benzo(a)pyrene and testosterone

    Energy Technology Data Exchange (ETDEWEB)

    Kao, J.; Patterson, F.K.; Hall, J.

    1985-12-01

    Because viable skin possesses enzyme activities, including those involved in the metabolism of xenobiotics, the extent to which cutaneous metabolism may influence the percutaneous fate of topically applied chemicals in the skin was examined in mammalian skin maintained as short-term organ cultures. Skin samples from mouse, rat, rabbit, guinea pig, marmoset, and man were examined. The results from studies with benzo(a)pyrene (BP) and testosterone showed that, in all species, metabolic viability was a major factor involved in the in vitro skin permeation of surface-applied chemicals. Permeation was accompanied by extensive cutaneous first pass metabolism; both parent compounds and a full spectrum of metabolites were found in the receptor fluid from viable skin preparations. However, in previously frozen nonviable skin preparations, essentially only unchanged parent compounds were detected in the receptor fluid. Permeation of BP and testosterone was highest in mouse skin, and significant species variations in the metabolite profiles were observed. Studies with mouse skin also demonstrated that induction of cutaneous drug-metabolizing enzymes can result in a two- to threefold increase in the in vitro permeation of topical BP, and a significant reduction in permeation was observed when KCN was added to the perfusion medium. These results indicate that diffusional and metabolic processes are intimately involved in the percutaneous fate of surface-applied chemicals. The relative importance of these processes is dependent upon the physicochemical properties of the compounds and the metabolic capabilities of the skin toward the compounds in question. Furthermore, these findings suggest that meaningful in vitro studies on skin absorption should consider both diffusion and cutaneous biotransformation of the applied compound.

  2. Combination chemoprevention with diclofenac, calcipotriol and difluoromethylornithine inhibits development of non-melanoma skin cancer in mice

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Burcharth, Jakob; Rosenberg, Jacob

    2013-01-01

    Background/Aim: With increasing incidence of non-melanoma skin cancer (NMSC), focus on chemoprevention of this disease is growing. The aim of this study was to evaluate topical combination therapies as chemoprevention of UV radiation-induced tumors in a mouse model....

  3. RIKEN mouse genome encyclopedia.

    Science.gov (United States)

    Hayashizaki, Yoshihide

    2003-01-01

    We have been working to establish the comprehensive mouse full-length cDNA collection and sequence database to cover as many genes as we can, named Riken mouse genome encyclopedia. Recently we are constructing higher-level annotation (Functional ANnoTation Of Mouse cDNA; FANTOM) not only with homology search based annotation but also with expression data profile, mapping information and protein-protein database. More than 1,000,000 clones prepared from 163 tissues were end-sequenced to classify into 159,789 clusters and 60,770 representative clones were fully sequenced. As a conclusion, the 60,770 sequences contained 33,409 unique. The next generation of life science is clearly based on all of the genome information and resources. Based on our cDNA clones we developed the additional system to explore gene function. We developed cDNA microarray system to print all of these cDNA clones, protein-protein interaction screening system, protein-DNA interaction screening system and so on. The integrated database of all the information is very useful not only for analysis of gene transcriptional network and for the connection of gene to phenotype to facilitate positional candidate approach. In this talk, the prospect of the application of these genome resourced should be discussed. More information is available at the web page: http://genome.gsc.riken.go.jp/.

  4. Mouse models in oncoimmunology.

    Science.gov (United States)

    Zitvogel, Laurence; Pitt, Jonathan M; Daillère, Romain; Smyth, Mark J; Kroemer, Guido

    2016-12-01

    Fundamental cancer research and the development of efficacious antineoplastic treatments both rely on experimental systems in which the relationship between malignant cells and immune cells can be studied. Mouse models of transplantable, carcinogen-induced or genetically engineered malignancies - each with their specific advantages and difficulties - have laid the foundations of oncoimmunology. These models have guided the immunosurveillance theory that postulates that evasion from immune control is an essential feature of cancer, the concept that the long-term effects of conventional cancer treatments mostly rely on the reinstatement of anticancer immune responses and the preclinical development of immunotherapies, including currently approved immune checkpoint blockers. Specific aspects of pharmacological development, as well as attempts to personalize cancer treatments using patient-derived xenografts, require the development of mouse models in which murine genes and cells are replaced with their human equivalents. Such 'humanized' mouse models are being progressively refined to characterize the leukocyte subpopulations that belong to the innate and acquired arms of the immune system as they infiltrate human cancers that are subjected to experimental therapies. We surmise that the ever-advancing refinement of murine preclinical models will accelerate the pace of therapeutic optimization in patients.

  5. Isolation of Mouse Neutrophils.

    Science.gov (United States)

    Swamydas, Muthulekha; Luo, Yi; Dorf, Martin E; Lionakis, Michail S

    2015-08-03

    Neutrophils represent the first line of defense against bacterial and fungal pathogens. Indeed, patients with inherited and acquired qualitative and quantitative neutrophil defects are at high risk for developing bacterial and fungal infections and suffering adverse outcomes from these infections. Therefore, research aiming at defining the molecular factors that modulate neutrophil effector function under homeostatic conditions and during infection is essential for devising strategies to augment neutrophil function and improve the outcome of infected individuals. This unit describes a reproducible density gradient centrifugation-based protocol that can be applied in any laboratory to harvest large numbers of highly enriched and highly viable neutrophils from the bone marrow of mice both at the steady state and following infection with Candida albicans as described in UNIT. In another protocol, we also present a method that combines gentle enzymatic tissue digestion with a positive immunomagnetic selection technique or Fluorescence-activated cell sorting (FACS) to harvest highly pure and highly viable preparations of neutrophils directly from mouse tissues such as the kidney, the liver or the spleen. Finally, methods for isolating neutrophils from mouse peritoneal fluid and peripheral blood are included. Mouse neutrophils isolated by these protocols can be used for examining several aspects of cellular function ex vivo including pathogen binding, phagocytosis and killing, neutrophil chemotaxis, oxidative burst, degranulation and cytokine production, and for performing neutrophil adoptive transfer experiments.

  6. Autoimmune Skin Diseases in the Dog

    OpenAIRE

    Parker, W. M.

    1981-01-01

    Diagnoses of autoimmune skin diseases require very careful observation of the skin lesions, and selection of an intact vesicle for histopathological examination. If available, immunofluorescent studies can be very useful in confirming the diagnosis of autoimmune skin disease. Seven autoimmune skin diseases are briefly reviewed. Therapy must be aggressive and owner warned of the guarded prognosis.

  7. 7 CFR 51.1549 - Skinning.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Skinning. 51.1549 Section 51.1549 Agriculture... Standards for Grades of Potatoes 1 Skinning § 51.1549 Skinning. (a) The following definitions provide a basis for describing lots of potatoes as to the degree of skinning whenever description may...

  8. ACKR4 on Stromal Cells Scavenges CCL19 To Enable CCR7-Dependent Trafficking of APCs from Inflamed Skin to Lymph Nodes.

    Science.gov (United States)

    Bryce, Steven A; Wilson, Ruairi A M; Tiplady, Eleanor M; Asquith, Darren L; Bromley, Shannon K; Luster, Andrew D; Graham, Gerard J; Nibbs, Robert J B

    2016-04-15

    Dermal dendritic cells and epidermal Langerhans cells are APCs that migrate from skin to draining lymph nodes (LN) to drive peripheral tolerance and adaptive immunity. Their migration requires the chemokine receptor CCR7, which directs egress from the skin via dermal lymphatic vessels and extravasation into the LN parenchyma from lymph in the subcapsular sinus. CCR7 is activated by two chemokines: CCL19 and CCL21. CCL21 alone is sufficient for the migration of APCs from skin to LN. CCL19 and CCL21 also bind atypical chemokine receptor (ACKR) 4. ACKR4-mediated CCL21 scavenging by lymphatic endothelial cells lining the subcapsular sinus ceiling stabilizes interfollicular CCL21 gradients that direct lymph-borne CCR7(+)APCs into the parenchyma of mouse LN. In this study, we show that ACKR4 also aids APC egress from mouse skin under steady-state and inflammatory conditions. ACKR4 plays a particularly prominent role during cutaneous inflammation when it facilitates Langerhans cell egress from skin and enables the accumulation of dermal dendritic cells in skin-draining LN. Stromal cells in mouse skin, predominantly keratinocytes and a subset of dermal lymphatic endothelial cells, express ACKR4 and are capable of ACKR4-dependent chemokine scavenging in situ. ACKR4-mediated scavenging of dermal-derived CCL19, rather than CCL21, is critical during inflammation, because the aberrant trafficking of skin-derived APCs inAckr4-deficient mice is completely rescued by genetic deletion ofCcl19 Thus, ACKR4 on stromal cells aids the egress of APCs from mouse skin, and, during inflammation, facilitates CCR7-dependent cell trafficking by scavenging CCL19.

  9. Skin interaction with absorbent hygiene products.

    Science.gov (United States)

    Runeman, Bo

    2008-01-01

    Skin problems due to the use of absorbent hygiene products, such as diapers, incontinence pads, and feminine sanitary articles, are mostly due to climate or chafing discomfort. If these conditions are allowed to prevail, these may develop into an irritant contact dermatitis and eventually superficial skin infections. Skin humidity and aging skin are among the most significant predisposing and aggravating factors for dermatitis development. Improved product design features are believed to explain the decline in observed diaper dermatitis among infants. Where adult incontinence-related skin problems are concerned, it is very important to apply a holistic perspective to understand the influences due to the individual's incontinence level and skin condition, as well as the hygiene and skin care measures provided. Individuals with frail, sensitive skin or with skin diseases may preferably have to use high-quality products, equipped with superabsorbent polymers and water vapor-permeable back sheets, to minimize the risk of skin complications.

  10. Self-reported skin morbidity in Denmark

    DEFF Research Database (Denmark)

    Miller, Iben Marie; Zarchi, Kian; Ellervik, Christina

    2016-01-01

    Skin diseases are thought to be common in the general population. In 2004, a cross-sectional study in Norway, using a validated questionnaire for 18,770 individuals, revealed a high prevalence of skin diseases in the general population. To describe the prevalence of self-reported skin morbidities...... questionnaire. In total, 17.2% self-reported skin complaints. The most prominent self-reported skin complaint was itch with an overall prevalence of 6.5%. The skin morbidity most influenced by age was pimples. There was a uniform pattern showing fewer skin complaints with increasing education. Women reported...... skin morbidities more frequently than men. Participants in employment reported fewer skin morbidities compared to unemployed participants. Skin morbidities in Denmark are common, and the distribution of prevalence estimates in the Danish population parallel those of the Norwegian population, although...

  11. Reconstruction of the penile skin loss due to 'radical' circumcision with a full thickness skin graft

    Directory of Open Access Journals (Sweden)

    Ignjatović Ivan

    2010-01-01

    Full Text Available Background. Excessive resection of penile skin is a rare but important complication of circumcision. Penis 'trapping' under the skin and consequent sexual dysfunction occur as a result. Case report. Excessive circumcision with complete resection of the penile skin is shown. Penis, trapped under the skin, was deliberated and skin defect was substituted with the full thickness skin graft. One year after the surgery penis has a good cosmetic appearance, adequate size and sexual function. Conclusion. Full thickness skin graft is a good option for augmentation of the penile skin loss in cases with intact hypodermal tissue and extensive skin loss, for the reconstruction in a single act.

  12. Skin Cancer and UV Protection

    Directory of Open Access Journals (Sweden)

    Tarbuk Anita

    2016-03-01

    Full Text Available The incidence of skin cancer is increasing by epidemic proportions. Basal cell cancer remains the most common skin neoplasm, and simple excision is generally curative. On the other hand, aggressive local growth and metastasis are common features of malignant melanoma, which accounts for 75% of all deaths associated with skin cancer. The primary cause of skin cancer is long exposure to solar ultraviolet radiation (UV-R crossed with the amount of skin pigmentation and family genetics. It is believed that in childhood and adolescence, 80% of UV-R gets absorbed while in the remaining, 20 % gets absorbed later in the lifetime. This suggests that proper and early photoprotection may reduce the risk of subsequent occurrence of skin cancer. Reducing the exposure time to sunlight, using sunscreens and protective textiles are the three ways of UV protection. Most people think that all the clothing will protect them, but it does not provide full sun screening properties. Literature sources claim that only 1/3 of the spring and summer collections tested give off proper UV protection. This is very important during the summer months, when UV index is the highest. Fabric UV protection ability highly depends on large number of factors such as type of fiber, fabric surface, construction, porosity, density, moisture content, type and concentration of dyestuff, fluorescent whitening agents, UV-B protective agents (UV absorbers, as well as nanoparticles, if applied. For all of these reasons, in the present paper, the results of UV protecting ability according to AS/NZS 4399:1996 will be discussed to show that standard clothing materials are not always adequate to prevent effect of UV-R to the human skin; and to suggest the possibilities for its improvement for this purpose enhancing light conversion and scattering. Additionally, the discrepancy in UV protection was investigated in distilled water as well as Adriatic Sea water.

  13. Skin Findings in Williams Syndrome

    Science.gov (United States)

    Kozel, Beth A.; Bayliss, Susan J.; Berk, David R.; Waxler, Jessica L; Knutsen, Russell H.; Danback, Joshua R.; Pober, Barbara R.

    2014-01-01

    Previous examination in a small number of individuals with Williams syndrome (also referred to as Williams-Beuren syndrome) has shown subtly softer skin and reduced deposition of elastin, an elastic matrix protein important in tissue recoil. No quantitative information about skin elasticity in individuals with Williams syndrome is available; nor has there been a complete report of dermatologic findings in this population. To fill this knowledge gap, 94 patients with Williams syndrome aged 7-50 years were recruited as part of the Skin and Vascular Elasticity (WS-SAVE) study. They underwent either a clinical dermatologic assessment by trained dermatologists (2010 WSA family meeting) or measurement of biomechanical properties of the skin with the DermaLab™ suction cup (2012 WSA family meeting). Clinical assessment confirmed that soft skin is common in this population (83%), as is premature graying of the hair (80% of those 20 years or older), while wrinkles (92%) and abnormal scarring (33%) were detected in larger than expected proportions. Biomechanical studies detected statistically significant differences in dP (the pressure required to lift the skin), dT (the time required to raise the skin through a prescribed gradient), VE (viscoelasticity) and E (Young’s modulus) relative to matched controls. The RT (retraction time) also trended longer but was not significant. The biomechanical differences noted in these patients did not correlate with the presence of vascular defects also attributable to elastin insufficiency (vascular stiffness, hypertension, and arterial stenosis) suggesting the presence of tissue specific modifiers that modulate the impact of elastin insufficiency in each tissue. PMID:24920525

  14. The current management of skin tears.

    Science.gov (United States)

    Xu, Xiaoti; Lau, Kwan; Taira, Breena R; Singer, Adam J

    2009-07-01

    Each year, there are more than 1 million skin tears among the elderly and disabled. Because of their fragile nature, management of skin tears can be very challenging. Methods of wound closure should minimize additional trauma to the skin and promote an optimal wound healing environment while minimizing the risk of infection. The current article reviews the etiology, risk factors, classification, and therapeutic options for treating skin tears. We also review preventive measures to help reduce the incidence of skin tears.

  15. MR imaging manifestations of skin tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong-hyon; Kim, Jee Young [The Catholic University of Korea, Department of Diagnostic Radiology, St. Vincent' s Hospital, Suwon, Gyeonggi-do (Korea); Chun, Kyung Ah [The Catholic University of Korea, Department of Diagnostic Radiology, Uijeongbu St. Mary Hospital, Uijeongbu, Gyeonggi-do (Korea); Jee, Won-Hee [The Catholic University of Korea, Department of Diagnostic Radiology, Kangnam St. Mary' s Hospital, Seoul (Korea); Sung, Mi-Sook [The Catholic University of Korea, Department of Diagnostic Radiology, Holy family Hospital, Bucheon, Gyeonggi-do (Korea)

    2008-11-15

    In this study, we evaluated MR imaging findings of skin tumors and categorized them into four types: (1) discrete mass lesions of the dermis and epidermis, (2) mass lesions of the subcutis with or without abutment to the skin, (3) diffuse or localized skin thickening without a true mass, and (4) a skin mass with bone destruction. The categorization of MR images may be useful in the differential diagnosis of skin tumors. (orig.)

  16. Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization

    Energy Technology Data Exchange (ETDEWEB)

    Alves, Vinicius M. [Laboratory of Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO 74605-220 (Brazil); Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Muratov, Eugene [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Laboratory of Theoretical Chemistry, A.V. Bogatsky Physical–Chemical Institute NAS of Ukraine, Odessa 65080 (Ukraine); Fourches, Denis [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States); Strickland, Judy; Kleinstreuer, Nicole [ILS/Contractor supporting the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), P.O. Box 13501, Research Triangle Park, NC 27709 (United States); Andrade, Carolina H. [Laboratory of Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiânia, GO 74605-220 (Brazil); Tropsha, Alexander, E-mail: alex_tropsha@unc.edu [Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599 (United States)

    2015-04-15

    Skin permeability is widely considered to be mechanistically implicated in chemically-induced skin sensitization. Although many chemicals have been identified as skin sensitizers, there have been very few reports analyzing the relationships between molecular structure and skin permeability of sensitizers and non-sensitizers. The goals of this study were to: (i) compile, curate, and integrate the largest publicly available dataset of chemicals studied for their skin permeability; (ii) develop and rigorously validate QSAR models to predict skin permeability; and (iii) explore the complex relationships between skin sensitization and skin permeability. Based on the largest publicly available dataset compiled in this study, we found no overall correlation between skin permeability and skin sensitization. In addition, cross-species correlation coefficient between human and rodent permeability data was found to be as low as R{sup 2} = 0.44. Human skin permeability models based on the random forest method have been developed and validated using OECD-compliant QSAR modeling workflow. Their external accuracy was high (Q{sup 2}{sub ext} = 0.73 for 63% of external compounds inside the applicability domain). The extended analysis using both experimentally-measured and QSAR-imputed data still confirmed the absence of any overall concordance between skin permeability and skin sensitization. This observation suggests that chemical modifications that affect skin permeability should not be presumed a priori to modulate the sensitization potential of chemicals. The models reported herein as well as those developed in the companion paper on skin sensitization suggest that it may be possible to rationally design compounds with the desired high skin permeability but low sensitization potential. - Highlights: • It was compiled the largest publicly-available skin permeability dataset. • Predictive QSAR models were developed for skin permeability. • No concordance between skin

  17. The effect of various dietary fats on skin tumor initiation.

    Science.gov (United States)

    Locniskar, M; Belury, M A; Cumberland, A G; Patrick, K E; Fischer, S M

    1991-01-01

    The type of dietary fat has been shown to modulate the initiation stage of mammary tumorigenesis, with saturated fat fed before and/or during carcinogen treatment resulting in increased tumor incidence. This study was designed to determine whether different types of dietary fat alter the initiation stage of skin carcinogenesis by use of the initiation-promotion mouse skin carcinogenesis model. Sencar mice were divided into three groups and maintained on one of the experimental diets. The AIN-76-based diets consisted of 10% total fat with various types of fat: 8.5% menhaden oil plus 1.5% corn oil, 8.5% coconut oil plus 1.5% corn oil, and 10% corn oil. After three weeks mice were initiated with 10 nmol dimethylbenz[a]anthracene (DMBA). Two weeks later, all mice were switched to a diet containing 5% corn oil. Promotion began four weeks after initiation with twice-weekly application of 1 microgram 12-O-tetradecanoylphorbol-13-acetate and continued for 12 weeks. No statistically significant differences in kilocalories of food consumed or body weights were observed between diet groups during the study. The final papilloma incidence, yield, and size were not significantly different among the diet groups. In a parallel study, [3H]DMBA binding to epidermal DNA showed no dietary differences. Unlike the mammary carcinogenesis model, these data suggest that the type of fat fed during DMBA initiation had minimal effects on this stage of skin carcinogenesis.

  18. Mouse genetics: catalogue and scissors.

    Science.gov (United States)

    Sung, Young Hoon; Baek, In-Jeoung; Seong, Je Kyung; Kim, Jin Soo; Lee, Han-Woong

    2012-12-01

    Phenotypic analysis of gene-specific knockout (KO) mice has revolutionized our understanding of in vivo gene functions. As the use of mouse embryonic stem (ES) cells is inevitable for conventional gene targeting, the generation of knockout mice remains a very time-consuming and expensive process. To accelerate the large-scale production and phenotype analyses of KO mice, international efforts have organized global consortia such as the International Knockout Mouse Consortium (IKMC) and International Mouse Phenotype Consortium (IMPC), and they are persistently expanding the KO mouse catalogue that is publicly available for the researches studying specific genes of interests in vivo. However, new technologies, adopting zinc-finger nucleases (ZFNs) or Transcription Activator-Like Effector (TALE) Nucleases (TALENs) to edit the mouse genome, are now emerging as valuable and effective shortcuts alternative for the conventional gene targeting using ES cells. Here, we introduce the recent achievement of IKMC, and evaluate the significance of ZFN/TALEN technology in mouse genetics.

  19. Mouse genetics: Catalogue and scissors

    Directory of Open Access Journals (Sweden)

    Han-Woong Lee

    2012-12-01

    Full Text Available Phenotypic analysis of gene-specific knockout (KO mice hasrevolutionized our understanding of in vivo gene functions. Asthe use of mouse embryonic stem (ES cells is inevitable forconventional gene targeting, the generation of knockout miceremains a very time-consuming and expensive process. Toaccelerate the large-scale production and phenotype analyses ofKO mice, international efforts have organized global consortiasuch as the International Knockout Mouse Consortium (IKMCand International Mouse Phenotype Consortium (IMPC, andthey are persistently expanding the KO mouse catalogue that ispublicly available for the researches studying specific genes ofinterests in vivo. However, new technologies, adoptingzinc-finger nucleases (ZFNs or Transcription Activator-LikeEffector (TALE Nucleases (TALENs to edit the mouse genome,are now emerging as valuable and effective shortcuts alternativefor the conventional gene targeting using ES cells. Here, weintroduce the recent achievement of IKMC, and evaluate thesignificance of ZFN/TALEN technology in mouse genetics.

  20. Visualization of Malaria Parasites in the Skin Using the Luciferase Transgenic Parasite, Plasmodium berghei

    OpenAIRE

    Matsuoka, Hiroyuki; TOMITA, HIROYUKI; Hattori, Ryuta; Arai,Meiji; Hirai, Makoto

    2014-01-01

    We produced a transgenic rodent malaria parasite (Plasmodium berghei) that contained the luciferase gene under a promoter region of elongation factor-1α. These transgenic (TG) parasites expressed luciferase in all stages of their life cycle, as previously reported. However, we were the first to succeed in observing sporozoites as a mass in mouse skin following their deposition by the probing of infective mosquitoes. Our transgenic parasites may have emitted stronger bioluminescence than previ...

  1. A Comparative Analysis of Gene Expression Profiles during Skin Regeneration in Mus and Acomys

    OpenAIRE

    Brant, Jason Orr; Lopez, Maria-Cecilia; Baker, Henry V.; Barbazuk, W. Brad; Maden, Malcolm

    2015-01-01

    The African spiny mouse (Acomys spp.) can heal full thickness excisional skin wounds in a scar-free manner with regeneration of all dermal components including hair and associated structures. Comparing Acomys scar-free healing from Mus scarring identifies gene expression differences that discriminate these processes. We have performed an extensive comparison of gene expression profiles in response to 8mm full-thickness excisional wounds at days 3, 5, 7 and 14 post-wounding between Acomys and ...

  2. Therapeutic levels of erythropoietin (EPO) achieved after gene electrotransfer to skin in mice

    DEFF Research Database (Denmark)

    Gothelf, A; Hojman, P; Gehl, Julie

    2010-01-01

    Gene electrotransfer refers to gene transfection by electroporation and is an effective non-viral method for delivering naked DNA into cells and tissues. This study presents data from gene electrotransfer with erythropoietin (EPO) to mouse skin. Nine-week-old female NMRI mice received one, two...... or three intradermal injections of 50 microg EPO plasmid and were subsequently electroporated. With plate electrodes and 100 microg of EPO, a significant increase in hemoglobin (P...

  3. Perforating disorders of the skin

    Directory of Open Access Journals (Sweden)

    Kalpana Arora

    2013-01-01

    Full Text Available Background: Perforating disorders of the skin, is an often overlooked entity characterized by transepidermal elimination of material from the upper dermis and are classified histopathologically according to the type of epidermal disruption and the nature of the eliminated material. They include Kyrle′s disease, perforating folliculitis, reactive perforating collagenosis, and elastosis perforans serpiginosa. Aim: The aim of this study was to delineate the clinical and histopathological features of perforating disorders of the skin. Materials and Methods: In our study, we reviewed last 2 years skin biopsies received by us. Hematoxylin and eosin sections were re-examined and histochemical stainings (elastic van Gieson and Masson trichrome stains were also used for histopathological evaluation. Results: We reviewed five cases of perforating disorders of skin which included two cases of Kyrle′s disease, two cases of reactive perforating collagenosis and a single case of perforating folliculitis. Two patients had family history of perforating dermatosis in their siblings and three had associated systemic disease. Conclusion: Perforating disorders of the skin should be considered when ulcer with keratotic plugs is found.

  4. Mouse models of medulloblastoma

    Institute of Scientific and Technical Information of China (English)

    Xiaochong Wu; Paul A. Northcott; Sidney Croul; Michael D. Taylor

    2011-01-01

    Medulloblastoma is the most common malignant pediatric brain tumor. Despite its prevalence and importance in pediatric neuro-oncology, the genes and pathways responsible for its initiation, maintenance,and progression remain poorly understood. Genetically engineered mouse models are an essential tool for uncovering the molecular and cellular basis of human diseases, including cancer, and serve a valuable role as preclinical models for testing targeted therapies. In this review, we summarize how such models have been successfully applied to the study of medulloblastoma over the past decade and what we might expect in the coming years.

  5. Ectodermal Dysplasia Skin Fragility Syndrome

    Directory of Open Access Journals (Sweden)

    Ayça Alan Atalay

    2014-06-01

    Full Text Available Ectodermal dysplasia-skin fragility syndrome (EDSFS is a rare autosomal recessive genodermatosis first described in 1997 by Mc Grath. EDSFS results from loss of function mutations in plakophilin-1 (PKP1. PKP1 is a structural component of desmosomes, cellcell adhesion complexes. It is also found as a nuclear protein in several cell types that are lack of desmosomes. In skin, however, PKP1 expression is confined mainly to suprabasal keratinocytes and the outer root sheath of hair follicules. Loss of function mutation in PKP1 leads to extensive skin fragility, bullae and erosions following minor trauma, focal keratoderma with painful fissures, alopecia, and nail dystrophy. In some patients hypohidrosis may also be seen. EDSFS is now considered as a specific suprabasal form of epidermolysis bullosa simplex. In this report we describe a 20 year old EDSFS case.

  6. Animal models of skin regeneration.

    Science.gov (United States)

    Gawronska-Kozak, Barbara; Grabowska, Anna; Kopcewicz, Marta; Kur, Anna

    2014-03-01

    Cutaneous injury in the majority of vertebrate animals results in the formation of a scar in the post-injured area. Scar tissues, although beneficial for maintaining integrity of the post-wounded region often interferes with full recovery of injured tissues. The goal of wound-healing studies is to identify mechanisms to redirect reparative pathways from debilitating scar formation to regenerative pathways that lead to normal functionality. To perform such studies models of regeneration, which are rare in mammals, are required. In this review we discussed skin regenerative capabilities present in lower vertebrates and in models of skin scar-free healing in mammals, e.g. mammalian fetuses. However, we especially focused on the attributes of two unusual models of skin scar-free healing capabilities that occur in adult mammals, that is, those associated with nude, FOXN1-deficient mice and in wild-type African spiny mice.

  7. Management of Acute Skin Trauma

    Institute of Scientific and Technical Information of China (English)

    Joel W. Beam

    2010-01-01

    @@ Acute skin trauma (ie, abrasions, avulsions, blisters, incisions, lacerations, and punctures) is common among individuals involved in work, recreational, and athletic activities. Appropriate management of these wounds is important to promote healing and lessen the risk of cross-contamination and infection. Wound management techniques have undergone significant changes in the past 40 years but many clinicians continue to manage acute skin trauma with long-established, traditional techniques (ie, use of hydrogen peroxide, adhesive strips/patches, sterile gauze, or no dressing) that can delay healing and increase the risk of infection. The purpose of this review is to discuss evidence-based cleansing, debridement, and dressing techniques for the management of acute skin trauma.

  8. Surgical skin-marking techniques.

    Science.gov (United States)

    Granick, M S; Heckler, F R; Jones, E W

    1987-04-01

    Surgical skin-marking inks and dyes are in everyday use for designing and planning incisions in plastic and reconstructive surgery. We have traced the historical development of surgical skin-marking techniques from ancient times to the present. The biochemical characteristics of the commonly used marking agents are discussed. A three-part experiment utilizing a pig model was carried out to test the tissue inflammatory response to the various dyes and inks when used intradermally as tattoos, the persistence of such tattoos, and the ease of skin erasure for each of eight stains. Methylene blue and gentian violet are recommended as the best all-purpose marking agents. The use of proprietary inks is discouraged.

  9. Skin Ultrasound in Kaposi Sarcoma.

    Science.gov (United States)

    Carrascosa, R; Alfageme, F; Roustán, G; Suarez, M D

    2016-05-01

    The use of ultrasound imaging has recently been increasing in numerous dermatologic diseases. This noninvasive technique provides additional details on the structure and vascularization of skin lesions. Kaposi sarcoma is a vascular tumor that typically arises in the skin and mucosas. It can spread to lymph nodes and internal organs. We performed B-mode and color Doppler ultrasound studies in 3 patients with a clinical diagnosis of Kaposi sarcoma confirmed by histological examination. We found differences in the ultrasound pattern between nodular and plaque lesions, in both B-mode and color Doppler. We believe that skin ultrasound imaging could be a useful technique for studying cutaneous Kaposi sarcoma, providing additional information on the structural and vascular characteristics of the lesion.

  10. Ex vivo multiscale quantitation of skin biomechanics in wild-type and genetically-modified mice using multiphoton microscopy

    Science.gov (United States)

    Bancelin, Stéphane; Lynch, Barbara; Bonod-Bidaud, Christelle; Ducourthial, Guillaume; Psilodimitrakopoulos, Sotiris; Dokládal, Petr; Allain, Jean-Marc; Schanne-Klein, Marie-Claire; Ruggiero, Florence

    2015-12-01

    Soft connective tissues such as skin, tendon or cornea are made of about 90% of extracellular matrix proteins, fibrillar collagens being the major components. Decreased or aberrant collagen synthesis generally results in defective tissue mechanical properties as the classic form of Elhers-Danlos syndrome (cEDS). This connective tissue disorder is caused by mutations in collagen V genes and is mainly characterized by skin hyperextensibility. To investigate the relationship between the microstructure of normal and diseased skins and their macroscopic mechanical properties, we imaged and quantified the microstructure of dermis of ex vivo murine skin biopsies during uniaxial mechanical assay using multiphoton microscopy. We used two genetically-modified mouse lines for collagen V: a mouse model for cEDS harboring a Col5a2 deletion (a.k.a. pN allele) and the transgenic K14-COL5A1 mice which overexpress the human COL5A1 gene in skin. We showed that in normal skin, the collagen fibers continuously align with stretch, generating the observed increase in mechanical stress. Moreover, dermis from both transgenic lines exhibited altered collagen reorganization upon traction, which could be linked to microstructural modifications. These findings show that our multiscale approach provides new crucial information on the biomechanics of dermis that can be extended to all collagen-rich soft tissues.

  11. Influence of Clothing Fabrics on Skin Microcirculation

    Institute of Scientific and Technical Information of China (English)

    CHENG Ling; PAN Ning; ZHAO Lian-ying; HUAUNG Gu

    2010-01-01

    This study investigated the effects of clothing fabric on human skin microcirculation. Once skin is covered with a clothing fabric, human sensations, namely, coolness, warmth, softness, and roughness, are amused immediately, and the cutaneous micrecireulation may be changed consequently. Since the complex relationships of the human skin, the environment, and the clothing, there is few publication focusing on the physiological responses of the skin to the fabrics. In this paper, a Laser Doppler Flowmetry (LDF) was used to test the dynamic responses of the skin blood flow when the fabric was placed on the skin. Effects of different fabrics on the skin blood flux were investigated. The results show that cold stimulation of fabric has remarkable influences on the skin blood flux, and the surface properties of fabric are of importance to affect the human skin blood flow.

  12. How to improve skin notation

    DEFF Research Database (Denmark)

    Sartorelli, Pietro; Ahlers, Heinz W.; Alanko, Kristiina

    2007-01-01

    The ICOH Scientific Committee on Occupational and Environmental Dermatoses organized an International Workshop on “Dermal risk assessment at workplace” with the aim of focussing on the different ways of approaching the concept of skin notation (S) for chemicals. The Workshop participants presented...... their ideas on several aspects of S such as the problems related to the absorption through the compromised skin, the different approaches to S and models that can be used as alternatives to S. Participants agreed to produce a position paper with the goal of exploring the actions needed to improve the S system...

  13. Skin scoring in systemic sclerosis

    DEFF Research Database (Denmark)

    Zachariae, Hugh; Bjerring, Peter; Halkier-Sørensen, Lars

    1994-01-01

    Forty-one patients with systemic sclerosis were investigated with a new and simple skin score method measuring the degree of thickening and pliability in seven regions together with area involvement in each region. The highest values were, as expected, found in diffuse cutaneous systemic sclerosis...... (type III SS) and the lowest in limited cutaneous systemic sclerosis (type I SS) with no lesions extending above wrists and ancles. A positive correlation was found to the aminoterminal propeptide of type III procollagen, a serological marker for synthesis of type III collagen. The skin score...

  14. Penetration through the Skin Barrier

    DEFF Research Database (Denmark)

    Nielsen, Jesper Bo; Benfeldt, Eva; Holmgaard, Rikke

    2016-01-01

    The skin is a strong and flexible organ with barrier properties essential for maintaining homeostasis and thereby human life. Characterizing this barrier is the ability to prevent some chemicals from crossing the barrier while allowing others, including medicinal products, to pass at varying rates......-through diffusion cells) as well as in vivo methods (microdialysis and microperfusion). Then follows a discussion with examples of how different characteristics of the skin (age, site and integrity) and of the penetrants (size, solubility, ionization, logPow and vehicles) affect the kinetics of percutaneous...

  15. Clinical utility of skin karyotype

    Directory of Open Access Journals (Sweden)

    Luiza E. Dorfman

    2015-08-01

    Full Text Available ABSTRACTWe report the case of a patient with Patau syndrome, diagnosed by skin karyotype, emphasizing the applications and importance of this test. The pregnancy morphology ultrasound showed face defects and of central nervous system and heart chambers asymmetry. In the postnatal evaluation it was identified microcephaly, single central nostril, and other malformations. We performed skin karyotype that resulted in full trisomy 13. Our report highlights the possibility of performing karyotype examination in cases when it is no longer possible to obtain a blood sample, thus providing the correct diagnosis and genetic counseling for the family.

  16. [Skin-sparing mastectomies: how to avoid skin necrosis?].

    Science.gov (United States)

    Delbaere, M; Delaporte, T; Toussoun, G; Delay, E

    2008-04-01

    Skin-sparing mastectomy (SSM) has emerged as the surgical technique best adapted to the treatment of early breast cancers or breast cancer recurrences after conservative treatment; the technique is particularly appreciated by the patients who had been expecting the development of immediate, high-quality breast reconstruction for over 15 years. SSM preserves anatomical landmarks on the skin surface (notably the under-breast fold and the conical shape of the breast). The procedure must be performed by a skilled surgical team in order to maximize the quality of breast resection and reconstruction, particularly to avoid postoperative complications, notably damage to blood vessels within the skin flap and prosthesis infection. These complications generally affect the cosmetic outcome of the reconstruction, with serious short-term and long-term consequences for the acceptability of the surgical procedure, and may sometimes compromise the delivery of adjuvant treatments (either chemo- or radiotherapy). Based on our previous experience (1000 new cases since 1992), we will compare the advantages and drawbacks of the procedure, discuss its indications, describe the clinical situations encountered and the various specific interventions available, as well as the methods to reduce the risks of tissue damage and skin necrosis.

  17. Expression of a single, viral oncoprotein in skin epithelium is sufficient to recruit lymphocytes.

    Directory of Open Access Journals (Sweden)

    Allison Choyce

    Full Text Available Established cancers are frequently associated with a lymphocytic infiltrate that fails to clear the tumour mass. In contrast, the importance of recruited lymphocytes during premalignancy is less well understood. In a mouse model of premalignant skin epithelium, transgenic mice that express the human papillomavirus type 16 (HPV16 E7 oncoprotein under a keratin 14 promoter (K14E7 mice display epidermal hyperplasia and have a predominant infiltrate of lymphocytes consisting of both CD4 and CD8 T cells. Activated, but not naïve T cells, were shown to preferentially traffic to hyperplastic skin with an increased frequency of proliferative CD8+ T cells and CD4+ T cells expressing CCR6 within the tissue. Disruption of the interaction between E7 protein and retinoblastoma tumour suppressor protein (pRb led to reduced epithelial hyperplasia and T cell infiltrate. Finally, while K14E7 donor skin grafts are readily accepted onto syngeneic, non-transgenic recipients, these same skin grafts lacking skin-resident lymphocytes were rejected. Our data suggests that expression of a single oncoprotein in the epidermis is sufficient for lymphocyte trafficking (including immunosuppressive lymphocytes to premalignant skin.

  18. Andrographolide Sodium Bisulfate Prevents UV-Induced Skin Photoaging through Inhibiting Oxidative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Janis Ya-Xian Zhan

    2016-01-01

    Full Text Available Andrographolide sodium bisulfate (ASB, a water-soluble form made from andrographolide through sulfonating reaction, is an antioxidant and anti-inflammatory drug; however, the antiphotoaging effect of ASB has still not been revealed. Oxidative stress and inflammation are known to be responsible for ultraviolet (UV irradiation induced skin damage and consequently premature aging. In this study, we aimed at examining the effect of ASB on UV-induced skin photoaging of mice by physiological and histological analysis of skin and examination of skin antioxidant enzymes and immunity analyses. Results showed that topical administration of ASB suppressed the UV-induced skin thickness, elasticity, wrinkles, and water content, while ASB, especially at dose of 3.6 mg/mouse, increased the skin collagen content by about 53.17%, decreased the epidermal thickness by about 41.38%, and prevented the UV-induced disruption of collagen fibers and elastic fibers. Furthermore, ASB decreased MDA level by about 40.21% and upregulated the activities of SOD and CAT and downregulated the production of IL-1β, IL-6, IL-10, and TNF-α in UV-irradiated mice. Our study confirmed the protective effect of ASB against UV-induced photoaging and initially indicated that this effect can be attributed to its antioxidant and anti-inflammatory activities in vivo, suggesting that ASB may be a potential antiphotoaging agent.

  19. Enhanced in vitro and in vivo skin deposition of apigenin delivered using ethosomes.

    Science.gov (United States)

    Shen, Li-Na; Zhang, Yong-Tai; Wang, Qin; Xu, Ling; Feng, Nian-Ping

    2014-01-02

    The aim of this study was to develop and evaluate a novel topical delivery system for apigenin by using ethosomes. An optimal apigenin-loaded ethosome formulation was identified by means of uniform design experiments. Skin deposition and transdermal flux of apigenin loaded in ethosomes, liposomes, and deformable liposomes were compared in vitro and in vivo. The efficiency of apigenin encapsulation increased with an increase in the amount of phospholipids in ethosome formulations. Moreover, skin deposition and transdermal flux of apigenin improved with an increase in the levels of phospholipids (Lipoid S 75) and short-chain alcohols (propylene glycol and ethanol), but decreased with an increase in the ratio of propylene glycol to ethanol. Profiles of skin deposition versus time for ethosomes varied markedly between in vivo and in vitro studies compared with those of liposomes or deformable liposomes. Optimized ethosomes showed superior skin targeting both in vitro and in vivo. Moreover, they had the strongest effect on reduction of cyclooxygenase-2 levels in mouse skin inflammation induced by ultraviolet B (UVB) light. Therefore, apigenin-loaded ethosomes represent a promising therapeutic approach for the treatment of UVB-induced skin inflammation.

  20. Genome-wide expression profiling of five mouse models identifies similarities and differences with human psoriasis.

    Directory of Open Access Journals (Sweden)

    William R Swindell

    Full Text Available Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1. While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis.