WorldWideScience

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  3. Multistage chemical carcinogenesis in mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. Expression of naked DNA in human, pig, and mouse skin.

    OpenAIRE

    Hengge, U R; Walker, P. S.; Vogel, J. C.

    1996-01-01

    The insertion and expression of genes in the epidermis may have a variety of therapeutic uses, including the treatment of skin diseases. Here we show that when both human skin organ cultures and human skin grafts on immunocompromised mice are injected with naked DNA, the DNA is taken-up and genes are expressed in the epidermis in a manner similar to both pig skin injected in vivo and injected pig skin organ cultures. In contrast, DNA injected into mouse skin is expressed not just in the epide...

  5. Hyperelastic Material Properties of Mouse Skin under Compression.

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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.

  7. 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.

  8. Methodology for statistical analysis of SENCAR mouse skin assay data.

    OpenAIRE

    Stober, J A

    1986-01-01

    Various response measures and statistical methods appropriate for the analysis of data collected in the SENCAR mouse skin assay are examined. The characteristics of the tumor response data do not readily lend themselves to the classical methods for hypothesis testing. The advantages and limitations of conventional methods of analysis and methods recommended in the literature are discussed. Several alternative response measures that were developed specifically to answer the problems inherent i...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    OpenAIRE

    Jayanthi Manne; Marina Markova; Siracusa, Linda D.; Jimenez, Sergio A.

    2013-01-01

    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 t...

  13. 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.

  14. 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.

  15. Expression and Function of Group IIE Phospholipase A2 in Mouse Skin.

    Science.gov (United States)

    Yamamoto, Kei; Miki, Yoshimi; Sato, Hiroyasu; Nishito, Yasumasa; Gelb, Michael H; Taketomi, Yoshitaka; Murakami, Makoto

    2016-07-22

    Recent studies using knock-out mice for various secreted phospholipase A2 (sPLA2) isoforms have revealed their non-redundant roles in diverse biological events. In the skin, group IIF sPLA2 (sPLA2-IIF), an "epidermal sPLA2" expressed in the suprabasal keratinocytes, plays a fundamental role in epidermal-hyperplasic diseases such as psoriasis and skin cancer. In this study, we found that group IIE sPLA2 (sPLA2-IIE) was expressed abundantly in hair follicles and to a lesser extent in basal epidermal keratinocytes in mouse skin. Mice lacking sPLA2-IIE exhibited skin abnormalities distinct from those in mice lacking sPLA2-IIF, with perturbation of hair follicle ultrastructure, modest changes in the steady-state expression of a subset of skin genes, and no changes in the features of psoriasis or contact dermatitis. Lipidomics analysis revealed that sPLA2-IIE and -IIF were coupled with distinct lipid pathways in the skin. Overall, two skin sPLA2s, hair follicular sPLA2-IIE and epidermal sPLA2-IIF, play non-redundant roles in distinct compartments of mouse skin, underscoring the functional diversity of multiple sPLA2s in the coordinated regulation of skin homeostasis and diseases. PMID:27226633

  16. Topical Application of Oleuropein Induces Anagen Hair Growth in Telogen Mouse Skin.

    Directory of Open Access Journals (Sweden)

    Tao Tong

    Full Text Available Oleuropein promoted cultured human follicle dermal papilla cell proliferation and induced LEF1 and Cyc-D1 mRNA expression and β-catenin protein expression in dermal papilla cells. Nuclear accumulation of β-catenin in dermal papilla cells was observed after oleuropein treatment. Topical application of oleuropein (0.4 mg/mouse/day to C57BL/6N mice accelerated the hair-growth induction and increased the size of hair follicles in telogenic mouse skin. The oleuropein-treated mouse skin showed substantial upregulation of Wnt10b, FZDR1, LRP5, LEF1, Cyc-D1, IGF-1, KGF, HGF, and VEGF mRNA expression and β-catenin protein expression.These results demonstrate that topical oleuroepin administration induced anagenic hair growth in telogenic C57BL/6N mouse skin. The hair-growth promoting effect of oleuropein in mice appeared to be associated with the stimulation of the Wnt10b/β-catenin signaling pathway and the upregulation of IGF-1, KGF, HGF, and VEGF gene expression in mouse skin tissue.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  19. Imaging the electric field associated with mouse and human skin wounds

    OpenAIRE

    Nuccitelli, Richard; Nuccitelli, Pamela; Ramlatchan, Samdeo; Sanger, Richard; Smith, Peter J.S.

    2008-01-01

    We have developed a noninvasive instrument called the bioelectric field imager (BFI) for mapping the electric field between the epidermis and the stratum corneum near wounds in both mouse and human skin. Rather than touching the skin, the BFI vibrates a small metal probe with a displacement of 180 μm in air above the skin to detect the surface potential of the epidermis through capacitative coupling. Here we describe our first application of the BFI measuring the electric field between the st...

  20. 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.

  1. 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. PMID:27101274

  2. Histology and Ultrastructure of Transitional Changes in Skin Morphology in the Juvenile and Adult Four-Striped Mouse (Rhabdomys pumilio)

    OpenAIRE

    Eranée Stewart; Moyosore Salihu Ajao; Amadi Ogonda Ihunwo

    2013-01-01

    The four-striped mouse has a grey to brown coloured coat with four characteristic dark stripes interspersed with three lighter stripes running along its back. The histological differences in the skin of the juvenile and adult mouse were investigated by Haematoxylin and Eosin and Masson Trichrome staining, while melanocytes in the skin were studied through melanin-specific Ferro-ferricyanide staining. The ultrastructure of the juvenile skin, hair follicles, and melanocytes was also explored. I...

  3. 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.

  4. 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.

  5. 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.

  6. Histology and Ultrastructure of Transitional Changes in Skin Morphology in the Juvenile and Adult Four-Striped Mouse (Rhabdomys pumilio

    Directory of Open Access Journals (Sweden)

    Eranée Stewart

    2013-01-01

    Full Text Available The four-striped mouse has a grey to brown coloured coat with four characteristic dark stripes interspersed with three lighter stripes running along its back. The histological differences in the skin of the juvenile and adult mouse were investigated by Haematoxylin and Eosin and Masson Trichrome staining, while melanocytes in the skin were studied through melanin-specific Ferro-ferricyanide staining. The ultrastructure of the juvenile skin, hair follicles, and melanocytes was also explored. In both the juvenile and adult four-striped mouse, pigment-containing cells were observed in the dermis and were homogeneously dispersed throughout this layer. Apart from these cells, the histology of the skin of the adult four-striped mouse was similar to normal mammalian skin. In the juvenile four-striped mouse, abundant hair follicles of varying sizes were observed in the dermis and hypodermis, while hair follicles of similar size were only present in the dermis of adult four-striped mouse. Ultrastructural analysis of juvenile hair follicles revealed that the arrangement and differentiation of cellular layers were typical of a mammal. This study therefore provides unique transition pattern in the four-striped mouse skin morphology different from the textbook description of the normal mammalian skin.

  7. 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.

  8. 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

  9. 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.

  10. Quantitative measurements of oxidative stress in mouse skin induced by X-ray irradiation

    International Nuclear Information System (INIS)

    To find efficient methods to evaluate oxidative stress in mouse skin caused by X-ray irradiation, several markers and methodologies were examined. Hairless mice were irradiated with 50 Gy X-rays and skin homogenates or skin strips were prepared. Lipid peroxidation was measured using the skin homogenate as the level of thiobarbituric acid reactive substances. The level of lipid peroxidation increased with time after irradiation and was twice that of the control at 78 h. Electron spin resonance (ESR) spectra of skin strips showed a clear signal for the ascorbyl radical, which increased with time after irradiation in a manner similar to that of lipid peroxidation. To measure levels of glutathione (GSH) and its oxidized forms (GSSG) simultaneously, two high performance liquid chromatography (HPLC) methods, sample derivatization with 1-fluoro-2,4-dinitrobenzene and detection with a UV detector (method A) and no derivatization and detection with an electrochemical detector (method B), were compared and the latter was found to be better. No significant change was observed within 24 h after irradiation in the levels of GSH and GSSG measured by method B. The GSH/GSSG ratio may be a less sensitive parameter for the evaluation of acute oxidative stress caused by X-ray irradiation in the skin. Monitoring the ascorbyl radical seems to be a good way to evaluate oxidative stress in skin in vivo. (author)

  11. Arsenic-induced enhancement of ultraviolet radiation carcinogenesis in mouse skin: a dose-response study.

    OpenAIRE

    Burns, Fredric J.; Uddin, Ahmed N.; Wu, Feng; Nádas, Arthur; Rossman, Toby G.

    2004-01-01

    The present study was designed to establish the form of the dose-response relationship for dietary sodium arsenite as a co-carcinogen with ultraviolet radiation (UVR) in a mouse skin model. Hairless mice (strain Skh1) were fed sodium arsenite continuously in drinking water starting at 21 days of age at concentrations of 0.0, 1.25, 2.5, 5.0, and 10 mg/L. At 42 days of age, solar spectrum UVR exposures were applied three times weekly to the dorsal skin at 1.0 kJ/m2 per exposure until the experi...

  12. 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

  13. 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.

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

    Science.gov (United States)

    Jagetia, Ganesh Chandra; Rajanikant, Golgod Krishnamurthy

    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 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. PMID:26785336

  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. Mouse allergen-specific immunoglobulin G4 and risk of mouse skin test sensitivity

    NARCIS (Netherlands)

    E.C. Matsui; G.B. Diette; E.J.M. Krop; R.C. Aalberse; A.L. Smith; P.A. Eggleston

    2006-01-01

    Background High serum levels of cat-specific IgG and IgG4 are associated with protection against allergic sensitization to cat, but whether this association applies to other animal allergens remains unclear. Objective To determine if high levels of mouse-specific IgG and IgG4 are associated with a d

  18. The acute effects of different energy beta-emitters on pig and mouse skin

    International Nuclear Information System (INIS)

    Acute changes were studied in the skin of mice and pigs following irradiation with Sr90 (Esub(max) 2.27 MeV), Tm170 (Esub(max) 0.97 MeV) and Pm147 (Esub(max) 0.225 MeV). Sr90 irradiation in the pig and Sr90 and Tm170 exposure in the mouse resulted in a distinct field-size effect for sources of 5-22.5 mm diameter; ED50 values for moist desquamation were 22.0-27.5 Gy from the 22.5 mm source and 75-90 Gy for the 5 mm source. Tm170 irradiation in the pig produced no distinct area effect for sources of 5-19 mm diameter (ED50 approx.= 80 Gy). Acute tissue breakdown was only achieved in pig and mouse skin by very high doses (ED50 >= 140 Gy) from sources of 147 produced acute epithelial breakdown, only after high skin-surface doses (ED50 550-725 Gy). Area-and energy-related changes can, in part be explained by an hypothesis based on repopulation of the epithelium in the irradiated area by the migration of either cells from the edge of that area and/or cells surviving at the base of hair follicles. Differences in the results in pig and mouse can be explained on the basis of the distribution of target cells in the epidermis at varying depths. (author)

  19. 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.

  20. LC-ESI-MS method for the determination of dexamethasone acetate in skin of nude mouse.

    Science.gov (United States)

    Li, Lingjun; Ma, Pengcheng; Wei, Jun; Qian, Kun; Tao, Lei

    2013-08-15

    A high-performance liquid chromatography-positive electrospray ionization single quadrupole mass spectrometric (LC-ESI-MS) method for the determination of dexamethasone acetate in skin of nude mouse using triamcinolone acetonide acetate as the internal standard (I.S.) was developed and fully validated. Both compounds were precipitated from skin homogenate with methanol and were separated by HPLC on a Shimadzu Shim-pack VP-ODS C18 column (150mm×2.0mm, 5μm) with a mobile phase of methanol-water (80:20, v/v) at a flow rate of 0.2mL/min. Calibration curves were linear over the range of 0.05-5μg/mL. The intra-run relative standard deviations were less than 9.59%. The inter-run relative standard deviations were less than 7.82%. The mean recovery was in the ranges of 89.95-95.97%, respectively. The method was successfully applied to determinate the concentration of dexamethasone acetate in skin and study the percutaneous absorption process in skin of nude mouse. PMID:23867829

  1. 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.

  2. Reduction in squamous cell carcinomas in mouse skin by dietary zinc supplementation.

    Science.gov (United States)

    Sun, Jin; Shen, Rulong; Schrock, Morgan S; Liu, James; Pan, Xueliang; Quimby, Donald; Zanesi, Nicola; Druck, Teresa; Fong, Louise Y; Huebner, Kay

    2016-08-01

    Inadequate dietary Zn consumption increases susceptibility to esophageal and other cancers in humans and model organisms. Since Zn supplementation can prevent cancers in rodent squamous cell carcinoma (SCC) models, we were interested in determining if it could have a preventive effect in a rodent skin cancer model, as a preclinical basis for considering a role for Zn in prevention of human nonmelanoma skin cancers, the most frequent cancers in humans. We used the 7,12-dimethyl benzanthracene carcinogen/phorbol myristate acetate tumor promoter treatment method to induce skin tumors in Zn-sufficient wild-type and Fhit (human or mouse protein) knockout mice. Fhit protein expression is lost in >50% of human cancers, including skin SCCs, and Fhit-deficient mice show increased sensitivity to carcinogen induction of tumors. We hypothesized that: (1) the skin cancer burdens would be reduced by Zn supplementation; (2) Fhit(-/-) (Fhit, murine fragile histidine triad gene) mice would show increased susceptibility to skin tumor induction versus wild-type mice. 30 weeks after initiating treatment, the tumor burden was increased ~2-fold in Fhit(-/-) versus wild-type mice (16.2 versus 7.6 tumors, P < 0.001); Zn supplementation significantly reduced tumor burdens in Fhit(-/-) mice (males and females combined, 16.2 unsupplemented versus 10.3 supplemented, P = 0.001). Most importantly, the SCC burden was reduced after Zn supplementation in both strains and genders of mice, most significantly in the wild-type males (P = 0.035). Although the mechanism(s) of action of Zn supplementation in skin tumor prevention is not known in detail, the Zn-supplemented tumors showed evidence of reduced DNA damage and some cohorts showed reduced inflammation scores. The results suggest that mild Zn supplementation should be tested for prevention of skin cancer in high-risk human cohorts. PMID:27185213

  3. Cutaneous Surgical Denervation: A Method for Testing the Requirement for Nerves in Mouse Models of Skin Disease.

    Science.gov (United States)

    Peterson, Shelby C; Brownell, Isaac; Wong, Sunny Y

    2016-01-01

    Cutaneous somatosensory nerves function to detect diverse stimuli that act upon the skin. In addition to their established sensory roles, recent studies have suggested that nerves may also modulate skin disorders including atopic dermatitis, psoriasis and cancer. Here, we describe protocols for testing the requirement for nerves in maintaining a cutaneous mechanosensory organ, the touch dome (TD). Specifically, we discuss methods for genetically labeling, harvesting and visualizing TDs by whole-mount staining, and for performing unilateral surgical denervation on mouse dorsal back skin. Together, these approaches can be used to directly compare TD morphology and gene expression in denervated as well as sham-operated skin from the same animal. These methods can also be readily adapted to examine the requirement for nerves in mouse models of skin pathology. Finally, the ability to repeatedly sample the skin provides an opportunity to monitor disease progression at different stages and times after initiation. PMID:27404892

  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. Expression and significance of EGFR protein in model of radiation injury in mouse skin

    International Nuclear Information System (INIS)

    Objective: The expression of EGFR protein was studied by SABC immunohistochemistry in 40 cases of model of radiation injury in mouse skin. Methods: Experiment animals were divided into four groups according to radiation dose. Results: The positive rates were 27.0%, 49.3%, 72.2%, 87.6% in 5 Gy group, 15 Gy group, 30 Gy group, 45 Gy group respectively, showing significant difference (P < 0.01). While the positive rate was 10.8% in normal control group, with significant difference (P < 0.01) compared with each radiation group. Conclusion: The enhancement of expression of EGFR in accordance with the increasing of radiation dose in certain dose range might be one important factor related to c-erbB-1 gene activated and enlarged by radiation, and the overexpression of EGFR protein might be related to poor healing in radiation skin injury

  6. Life science research using positron annihilation spectroscopy: UV-irradiated mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Jean, Y.C. [Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 64110-2499 (United States)]. E-mail: jeany@umkc.edu; Chen, Hongmin [Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 64110-2499 (United States); Liu Guang [Department of Chemistry, University of Missouri-Kansas City, Kansas City, MO 64110-2499 (United States); Gadzia, Joseph E. [Dermatology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS 66103 (United States); Kansas Medical Clinic, Topeka, KS 66614 (United States)

    2007-02-15

    Positron annihilation spectroscopy (PAS) is applied to study mouse skin under different UV irradiations as a function of positron incident energy (0-30 keV). Significant variations in the depth profile of S parameter are observed in a period of hours and of days for UVA and UVB exposures, respectively. The high sensitivity of positron annihilation signals responding to UV irradiation shows that PAS may be developed as a new noninvasive technique for the detection of molecular damage in life science research.

  7. Mouse skin reactions to 40 MeV helium ion irradiation

    International Nuclear Information System (INIS)

    The change of mouse skin was recorded periodically. Mice are periodically sacrificed to obtain irradiated skin specimens. The specimens are made into microscopic study preparations. 4He ion radiation dose applied to the skin ranges from 2,000 rads to 12,000 rads. 40MeV 4He ion beam is fairly stable. The study was repeated four times in total. When the beam position is in the center of scattering foil, Cobalt-60 gamma ray calibrateb one rad corresponded to 20-23 scattering 4He ion count detected by a solid state detector placed in the direction of 40 degree to the axis of down stream beam. One rad also corresponded to 0.52-0.55 nano-Ampere Farady cnp current placed in the center axis 80 centi-meter apart from the target foil. Monitoring with Farady cup current is more consistent, in which beam deviation from the center can not be detected. Hence the dose was monitored with the current with scattering helium count recorded. Depth dose was measured with TLD and 50% depth dose of plateau is approximately 0.08 g/cm. The skin was irradiated from 2,000 rads to 12,000 rads. In one week epilation starts. In two week complete epilation in all groups and in high dose groups (above 4,000 rads) at the same time erosions occur. In four weeks erosions heal. Higher dose group takes a little longer. In five weeks all erosins heal any way. Even the skin irradiated with 12,000 rads heals. Skin hypertrophy follows. The higher dose induces the more hypertrophy. Cell number in a hair follicle decreases with increased dose. Hair follicle itself decreases its number. (J.P.N.)

  8. Anti-tumour promoting activity of diphenylmethyl selenocyanate against two-stage mouse skin carcinogenesis.

    Science.gov (United States)

    Das, Rajat Kumar; Bhattacharya, Sudin

    2005-01-01

    Epidemiological, clinical and experimental evidence collectively suggests that Se in different inorganic and organic forms provides a potential cancer chemopreventive agent, active against several types of cancer. It can exert preventive activity in all the three stages of cancer: initiation, promotion and progression. Literature reports revealed that organoselenocyanates have more potential as chemopreventive agents than inorganic forms due to their lower toxicity. In our previous report we showed chemopreventive efficacy of diphenylmethyl selenocyanate during the initiation and pre- plus post-initiation phases of skin and colon carcinogenesis process. The present study was undertaken to explore the anti-tumour promoting activity of diphenylmethyl selenocyanate in a 7,12-dimethylbenz (a) anthracene (DMBA)-croton oil two-stage skin carcinogenesis model. The results obtained showed significant (pliver and skin. Thus, the present data strongly suggest that diphenylmethyl selenocyanate also has the potential to act as anti-tumour promoter agent in a two-stage skin carcinogenesis mouse model, pointing to possible general efficacy. PMID:16101330

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

    International Nuclear Information System (INIS)

    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 [3H]-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-κB.

  10. 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

  11. Epithelial cell kinetics in mouse and rat skin irradiated with electrons

    International Nuclear Information System (INIS)

    Experiments were performed to examine the kinetic responses of mouse and rat epidermal cells in vivo after single doses of ionizing radiation including responses of hair follicles at times after irradiation. The labeling indices in both species were reduced to 30 to 50% of control values immediately following irradiation at all the doses. In the rat, the labeling indices recovered and overshot control values within the first three days after 300 to 1200 rads. The mouse labeling indices continued to be suppressed for up to 10 days after 300 to 2400 rads. This indicated that rat G1 phase epidermal cells recovered three times faster than those of the mouse with respect to the ability to maintain or increase control level cell proliferation after irradiation. After 1800 and 2400 rads, doses which produce skin ulceration, both species showed a reduction in their labeling indices for up to 7 days, indicating that a dose-dependent mechanism of recovery may be operable in the rat. 99 refs., 15 figs., 6 tabs

  12. 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.

  13. The co-application effects of fullerene and ascorbic acid on UV-B irradiated mouse skin

    International Nuclear Information System (INIS)

    The role of fullerene as a pro-oxidant or anti-oxidant in Ultraviolet B ray (UV-B)-induced disorders in mouse skin was investigated. Fullerene gave no photo-toxic effect to UV-B-irradiated mouse skin. Since erythema was concentrated at the pore circumference in a UV-B irradiation experiment in mouse skin, the sebaceous gland pairs was strongly implicated as a site for the generation of reactive oxygen species (ROS). In a histological evaluation of the skin stained with CH3MDFDA (ROS index) and YO-Pro-1 (apoptosis index), the fluorescence intensity of a sebaceous gland significantly increased with UV-B irradiation. With the application of fullerene to UV-irradiated mouse skin, no toxicity was recognized in comparison with the control, and erythema, the ROS index, and the apoptosis index decrease with the application of fullerene. Ascorbyl radical (AA·) increased with the application of ascorbate (AA) to UV-B-irradiated mouse skin, and AA· decreased with the application of fullerene. The co-application of AA and fullerene, which suppressed AA· in vitro, significantly suppressed erythema, and also suppressed both the ROS index and apoptosis index in mouse skin after UV-B irradiation. In both mouse skin at 48 h after UV-B irradiation and in an attempt to reproduce this phenomenon artificially in vitro, a similar high AA· peak (AA·/H· > 4) was observed in electron spin resonance (ESR) charts. The binding of fullerene with AA impairs the Fenton reaction between AA and Fe-protein based on the observation of ascorbate-specific UV absorption and a linear equation for the calibration curve. Therefore, fullerene may impair the intercalation of AA to a heme pocket by binding with AA. These results suggest that the co-application of AA and fullerene is effective against oxidative skin damage caused by UV-B irradiation, and the development of an AA· inhibitor such as fullerene should be useful for reducing organ damage associated with Fe-protein oxidation.

  14. Xenobiotic-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models

    OpenAIRE

    Oesch, F; Fabian, E.; Guth, K.; Landsiedel, R.

    2014-01-01

    Abstract The exposure of the skin to medical drugs, skin care products, cosmetics, and other chemicals renders information on xenobiotic-metabolizing enzymes (XME) in the skin highly interesting. Since the use of freshly excised human skin for experimental investigations meets with ethical and practical limitations, information on XME in models comes in the focus including non-human mammalian species and in vitro skin models. This review attempts to summarize the information available in the ...

  15. 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.

  16. Aloe arborescens extract inhibits TPA-induced ear oedema, putrescine increase and tumour promotion in mouse skin.

    Science.gov (United States)

    Shimpo, Kan; Ida, Chikako; Chihara, Takeshi; Beppu, Hidehiko; Kaneko, Takaaki; Kuzuya, Hiroshi

    2002-08-01

    The ethyl acetate extract of the acetone-soluble Aloe arborescens fraction was found to inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear oedema, putrescine increase and tumour promotion in mouse skin. Chromatographic analyses of this extract revealed that phenolic compounds such as aloenin, barbaloin and isobarbaloin could be useful as cancer chemopreventive agents against tumour promotion. PMID:12203274

  17. 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.

  18. Mechanisms of action of okadaic acid class tumor promoters on mouse skin

    Energy Technology Data Exchange (ETDEWEB)

    Fujiki, Hirota; Suganuma, Masami; Yoshizawa, Seiji; Nishiwaki, Shinji; Winyar, Boonsong (National Cancer Center Research Inst., Tokyo (Japan)); Sugimura, Takashi (National Cancer Center, Tokyo (Japan))

    1991-06-01

    Okadaic acid, dinophysistoxin-1 (35-methylokadaic acid), and calyculin A are the okadaic acid class of non-12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters, which do not bind to the phorbol ester receptors in cell membranes or activate protein kinase C in vitro. They have potent tumor-promoting activities on mouse skin, as strong as TPA-type tumor promoters, such as TPA, teleocidin, and aplysiatoxin. DNA samples isolated from tumors induced by dimethylbenz(a)anthracene and each of the okadaic acid class tumor promoters had the same mutation at the second nucleotide of codon 61 (CAA to CTA) in the c-H-ras gene. Okadaic acid receptors, protein phosphatases 1 and 2A, are present in the particulate as well as cytosolic fractions of various mouse tissues. The apparent activation of protein kinases by the okadaic acid class tumor promoters, after their incubation with {sup 32}P-ATP, protein kinases, and protein phosphatases, was observed. This activation was caused by inhibition of protein phosphatases 1 and 2A by the okadaic acid class tumor promoters. Treatment of primary human fibroblasts and human keratinocytes with the okadaic acid class tumor promoters induced the hyperphosphorylation of a 60-k-Da protein in nuclear and cytosolic fractions, due to the inhibition of protein phosphatases. The 60-kDa protein is a proteolytic fragment of nucleolin, a major nonhistone protein and is designated as N-60. The mechanisms of action of the okadaic acid class tumor promoters are discussed with emphasis on the inhibition of protein phosphatase activity.

  19. Multimodality pH imaging in a mouse dorsal skin fold window chamber model

    Science.gov (United States)

    Leung, Hui Min; Schafer, Rachel; Pagel, Mark M.; Robey, Ian F.; Gmitro, Arthur F.

    2013-03-01

    Upregulate levels of expression and activity of membrane H+ ion pumps in cancer cells drives the extracellular pH (pHe,) to values lower than normal. Furthermore, disregulated pH is indicative of the changes in glycolytic metabolism in tumor cells and has been shown to facilitate extracellular tissue remodeling during metastasis Therefore, measurement of pHe could be a useful cancer biomarker for diagnostic and therapy monitoring evaluation. Multimodality in-vivo imaging of pHe in tumorous tissue in a mouse dorsal skin fold window chamber (DSFWC) model is described. A custom-made plastic window chamber structure was developed that is compatible with both imaging optical and MR imaging modalities and provides a model system for continuous study of the same tissue microenvironment on multiple imaging platforms over a 3-week period. For optical imaging of pHe, SNARF-1 carboxylic acid is injected intravenously into a SCID mouse with an implanted tumor. A ratiometric measurement of the fluorescence signal captured on a confocal microscope reveals the pHe of the tissue visible within the window chamber. This imaging method was used in a preliminary study to evaluate sodium bicarbonate as a potential drug treatment to reverse tissue acidosis. For MR imaging of pHe the chemical exchange saturation transfer (CEST) was used as an alternative way of measuring pHe in a DSFWC model. ULTRAVIST®, a FDA approved x-ray/CT contrast agent has been shown to have a CEST effect that is pH dependent. A ratiometric analysis of water saturation at 5.6 and 4.2 ppm chemical shift provides a means to estimate the local pHe.

  20. In vivo characterization of early-stage radiation skin injury in a mouse model by two-photon microscopy.

    Science.gov (United States)

    Jang, Won Hyuk; Shim, Sehwan; Wang, Taejun; Yoon, Yeoreum; Jang, Won-Suk; Myung, Jae Kyung; Park, Sunhoo; Kim, Ki Hean

    2016-01-01

    Ionizing radiation (IR) injury is tissue damage caused by high energy electromagnetic waves such as X-ray and gamma ray. Diagnosis and treatment of IR injury are difficult due to its characteristics of clinically latent post-irradiation periods and the following successive and unpredictable inflammatory bursts. Skin is one of the many sensitive organs to IR and bears local injury upon exposure. Early-stage diagnosis of IR skin injury is essential in order to maximize treatment efficiency and to prevent the aggravation of IR injury. In this study, early-stage changes of the IR injured skin at the cellular level were characterized in an in vivo mouse model by two-photon microscopy (TPM). Various IR doses were applied to the mouse hind limbs and the injured skin regions were imaged daily for 6 days after IR irradiation. Changes in the morphology and distribution of the epidermal cells and damage of the sebaceous glands were observed before clinical symptoms. These results showed that TPM is sensitive to early-stage changes of IR skin injury and may be useful for its diagnosis. PMID:26755422

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

    Science.gov (United States)

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

    2016-01-01

    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. PMID:27626393

  2. 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.

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

    OpenAIRE

    Bewick, Guy S.; Banks, Robert W.

    2016-01-01

    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 co...

  4. 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.

  5. Combined effect of cyclin D3 expression and abrogation of cyclin D1 prevent mouse skin tumor development

    Science.gov (United States)

    Wang, Xian; Sistrunk, Christopher; Miliani de Marval, Paula L; Kim, Yongbaek

    2012-01-01

    We have previously demonstrated that ras-mediated skin tumorigenesis depends on signaling pathways that act preferentially through cyclin D1 and D2. Interestingly, the expression of cyclin D3 inhibits skin tumor development, an observation that conflicts with the oncogenic role of D-type cyclins in the mouse epidermis. Here, we show that simultaneous up and downregulation of particular members of the D-type cyclin family is a valuable approach to reduce skin tumorigenesis. We developed the K5D3/cyclin D1−/− compound mouse, which overexpresses cyclin D3 but lacks expression of cyclin D1 in the skin. Similar to K5D3 transgenic mice, keratinocytes from K5D3/cyclin D1−/− compound mice show a significant reduction of cyclin D2 levels. Therefore, this model allows us to determine the effect of cyclin D3 expression when combined with reduced or absent expression of the remaining two members of the D-type cyclin family in mouse epidermis. Our data show that induced expression of cyclin D3 compensates for the reduced level of cyclin D1 and D2, resulting in normal keratinocyte proliferation. However, simultaneous ablation of cyclin D1 and downregulation of cyclin D2 via cyclin D3 expression resulted in a robust reduction in ras-mediated skin tumorigenesis. We conclude that modulation of the levels of particular members of the D-type cyclin family could be useful to inhibit tumor development and, in particular, ras-mediated tumorigenesis. PMID:22214766

  6. 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.

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

    International Nuclear Information System (INIS)

    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. 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. 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. 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

  8. Induction of active melanocytes in mouse skin by carcinogens: a new method for detection of skin carcinogens.

    Science.gov (United States)

    Iwata, K; Inui, N; Takeuchi, T

    1981-01-01

    Application of potent skin carcinogens, such as 7,12-dimethylbenz[a]anthracene, 3-methylcholanthrene, benzo[a]pyrene and 4-nitroquinoline-1-oxide, induced numerous dihydroxyphenylalanine (dopa)-positive cells in the interfollicular epidermis of C57BL/6 mice in a dose- and time-dependent fashion. Chrysene, a weak skin carcinogen, and croton oil, a tumor promoter, also induced 3--4 times more dopa-positive cells than acetone. Liver carcinogens, such as 3'-methyl-4-dimethylaminoazobenzene and N-2-acetylaminofluorene, and non-carcinogenic aromatic hydrocarbons, such as anthracene, fluoranthene, fluorene and pyrene, did not induce increase in these cells. These results indicate that increase in the number of dopa-positive cells after application of chemicals is well correlated with the abilities of these compounds to induce skin carcinogenesis and suppress sebaceous glands. PMID:7273337

  9. CDK2 Activation in Mouse Epidermis Induces Keratinocyte Proliferation but Does Not Affect Skin Tumor Development

    Science.gov (United States)

    Macias, Everardo; Miliani de Marval, Paula L.; De Siervi, Adriana; Conti, Claudio J.; Senderowicz, Adrian M.; Rodriguez-Puebla, Marcelo L.

    2008-01-01

    It has been widely assumed that elevated CDK2 kinase activity plays a contributory role in tumorigenesis. We have previously shown that mice overexpressing CDK4 under control of the keratin 5 promoter (K5CDK4 mice) develop epidermal hyperplasia and increased susceptibility to squamous cell carcinomas. In this model, CDK4 overexpression results in increased CDK2 activity associated with the noncatalytic function of CDK4, sequestration of p21Cip1 and p27Kip1. Furthermore, we have shown that ablation of Cdk2 reduces Ras-Cdk4 tumorigenesis, suggesting that increased CDK2 activity plays an important role in Ras-mediated tumorigenesis. To investigate this hypothesis, we generated two transgenic mouse models of elevated CDK2 kinase activity, K5Cdk2 and K5Cdk4D158N mice. The D158N mutation blocks CDK4 kinase activity without interfering with its binding capability. CDK2 activation via overexpression of CDK4D158N, but not of CDK2, resulted in epidermal hyperplasia. We observed elevated levels of p21Cip1 in K5Cdk2, but not in K5Cdk4D158N, epidermis, suggesting that CDK2 overexpression elicits a p21Cip1 response to maintain keratinocyte homeostasis. Surprisingly, we found that neither CDK2 overexpression nor the indirect activation of CDK2 enhanced skin tumor development. Thus, although the indirect activation of CDK2 is sufficient to induce keratinocyte hyperproliferation, activation of CDK2 alone does not induce malignant progression in Ras-mediated tumorigenesis. PMID:18599613

  10. Differential Features between Chronic Skin Inflammatory Diseases Revealed in Skin-Humanized Psoriasis and Atopic Dermatitis Mouse Models.

    Science.gov (United States)

    Carretero, Marta; Guerrero-Aspizua, Sara; Illera, Nuria; Galvez, Victoria; Navarro, Manuel; García-García, Francisco; Dopazo, Joaquin; Jorcano, Jose Luis; Larcher, Fernando; del Rio, Marcela

    2016-01-01

    Psoriasis and atopic dermatitis are chronic and relapsing inflammatory diseases of the skin affecting a large number of patients worldwide. Psoriasis is characterized by a T helper type 1 and/or T helper type 17 immunological response, whereas acute atopic dermatitis lesions exhibit T helper type 2-dominant inflammation. Current single gene and signaling pathways-based models of inflammatory skin diseases are incomplete. Previous work allowed us to model psoriasis in skin-humanized mice through proper combinations of inflammatory cell components and disruption of barrier function. Herein, we describe and characterize an animal model for atopic dermatitis using similar bioengineered-based approaches, by intradermal injection of human T helper type 2 lymphocytes in regenerated human skin after partial removal of stratum corneum. In this work, we have extensively compared this model with the previous and an improved version of the psoriasis model, in which T helper type 1 and/or T helper type 17 lymphocytes replace exogenous cytokines. Comparative expression analyses revealed marked differences in specific epidermal proliferation and differentiation markers and immune-related molecules, including antimicrobial peptides. Likewise, the composition of the dermal inflammatory infiltrate presented important differences. The availability of accurate and reliable animal models for these diseases will contribute to the understanding of the pathogenesis and provide valuable tools for drug development and testing. PMID:26763433

  11. Progression of mouse skin carcinogenesis is associated with increased ERα levels and is repressed by a dominant negative form of ERα.

    Directory of Open Access Journals (Sweden)

    Stella Logotheti

    Full Text Available Estrogen receptors (ER, namely ERα and ERβ, are hormone-activated transcription factors with an important role in carcinogenesis. In the present study, we aimed at elucidating the implication of ERα in skin cancer, using chemically-induced mouse skin tumours, as well as cell lines representing distinct stages of mouse skin oncogenesis. First, using immunohistochemical staining we showed that ERα is markedly increased in aggressive mouse skin tumours in vivo as compared to the papilloma tumours, whereas ERβ levels are low and become even lower in the aggressive spindle tumours of carcinogen-treated mice. Then, using the multistage mouse skin carcinogenesis model, we showed that ERα gradually increases during promotion and progression stages of mouse skin carcinogenesis, peaking at the most aggressive stage, whereas ERβ levels only slightly change throughout skin carcinogenesis. Stable transfection of the aggressive, spindle CarB cells with a dominant negative form of ERα (dnERα resulted in reduced ERα levels and reduced binding to estrogen responsive elements (ERE-containing sequences. We characterized two highly conserved EREs on the mouse ERα promoter through which dnERα decreased endogenous ERα levels. The dnERα-transfected CarB cells presented altered protein levels of cytoskeletal and cell adhesion molecules, slower growth rate and impaired anchorage-independent growth in vitro, whereas they gave smaller tumours with extended latency period of tumour onset in vivo. Our findings suggest an implication of ERα in the aggressiveness of spindle mouse skin cancer cells, possibly through regulation of genes affecting cell shape and adhesion, and they also provide hints for the effective targeting of spindle cancer cells by dnERα.

  12. Cyclooxygenases in human and mouse skin and cultured human keratinocytes: association of COX-2 expression with human keratinocyte differentiation

    Science.gov (United States)

    Leong, J.; Hughes-Fulford, M.; Rakhlin, N.; Habib, A.; Maclouf, J.; Goldyne, M. E.

    1996-01-01

    Epidermal expression of the two isoforms of the prostaglandin H-generating cyclooxygenase (COX-1 and COX-2) was evaluated both by immunohistochemistry performed on human and mouse skin biopsy sections and by Western blotting of protein extracts from cultured human neonatal foreskin keratinocytes. In normal human skin, COX-1 immunostaining is observed throughout the epidermis whereas COX-2 immunostaining increases in the more differentiated, suprabasilar keratinocytes. Basal cell carcinomas express little if any COX-1 or COX-2 immunostaining whereas both isozymes are strongly expressed in squamous cell carcinomas deriving from a more differentiated layer of the epidermis. In human keratinocyte cultures, raising the extracellular calcium concentration, a recognized stimulus for keratinocyte differentiation, leads to an increased expression of both COX-2 protein and mRNA; expression of COX-1 protein, however, shows no significant alteration in response to calcium. Because of a recent report that failed to show COX-2 in normal mouse epidermis, we also looked for COX-1 and COX-2 immunostaining in sections of normal and acetone-treated mouse skin. In agreement with a previous report, some COX-1, but no COX-2, immunostaining is seen in normal murine epidermis. However, following acetone treatment, there is a marked increase in COX-1 expression as well as the appearance of significant COX-2 immunostaining in the basal layer. These data suggest that in human epidermis as well as in human keratinocyte cultures, the expression of COX-2 occurs as a part of normal keratinocyte differentiation whereas in murine epidermis, its constitutive expression is absent, but inducible as previously published.

  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. 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...

  15. Systemic morphine treatment induces changes in firing patterns and responses of nociceptive afferent fibers in mouse glabrous skin

    OpenAIRE

    Hogan, Dale; Baker, Alyssa L.; Morón, Jose A.; Carlton, Susan M.

    2013-01-01

    Patients receiving opioids for pain may experience decreased effectiveness of the drug and even abnormal pain sensitivity – either hyperalgesia and/or allodynia. We hypothesize that peripheral nociceptor hyperexcitability contributes to opioid-induced hyperalgesia and test this using an in vitro mouse glabrous skin-nerve preparation. Mice were injected i.p. with escalating doses of morphine (5, 8, 10, 15 mg/kg) or saline every 12 h for 48 h and sacrificed ~12 h following the last injection. R...

  16. Myeloid Cell Isolation from Mouse Skin and Draining Lymph Node Following Intradermal Immunization with Live Attenuated Plasmodium Sporozoites.

    Science.gov (United States)

    Mac-Daniel, Laura; Buckwalter, Matthew R; Gueirard, Pascale; Ménard, Robert

    2016-01-01

    Malaria infection begins when the sporozoite stage of Plasmodium is inoculated into the skin of a mammalian host through a mosquito bite. The highly motile parasite not only reaches the liver to invade hepatocytes and transform into erythrocyte-infective form. It also migrates into the skin and to the proximal lymph node draining the injection site, where it can be recognized and degraded by resident and/or recruited myeloid cells. Intravital imaging reported the early recruitment of brightly fluorescent Lys-GFP positive leukocytes in the skin and the interactions between sporozoites and CD11c(+) cells in the draining lymph node. We present here an efficient procedure to recover, identify and enumerate the myeloid cell subsets that are recruited to the mouse skin and draining lymph node following intradermal injection of immunizing doses of sporozoites in a murine model. Phenotypic characterization using multi-parametric flow cytometry provides a reliable assay to assess early dynamic cellular changes during inflammatory response to Plasmodium infection. PMID:27286053

  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

    2013-09-01

    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. DOSE-RESPONSE STUDIES OF SODIUM ARSENITE IN THE SKIN OF K6/ODC TRANSGENIC MOUSE

    Science.gov (United States)

    It has previously been observed that chronic exposure to inorganic arsenic and/or its metabolites increase(s) tumor frequency in the skin of K6/ODC transgenic mice. To identify potential biomarkers and modes of action for this skin tumorigenicity, gene expression profiles w...

  20. 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.

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

    Science.gov (United States)

    Quigley, David A; Kandyba, Eve; Huang, Phillips; Halliwill, Kyle D; Sjölund, Jonas; Pelorosso, Facundo; Wong, Christine E; Hirst, Gillian L; Wu, Di; Delrosario, Reyno; Kumar, Atul; Balmain, Allan

    2016-07-26

    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. PMID:27425619

  2. 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. PMID:27389473

  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. Effects of Intense Pulsed Light on Tissue Vascularity and Wound Healing: A Study with Mouse Island Skin Flap Model

    Directory of Open Access Journals (Sweden)

    Trinh Cao Minh

    2015-01-01

    Full Text Available Intense pulsed light (IPL has been used extensively in aesthetic and cosmetic dermatology. To test whether IPL could change the tissue vascularity and improve wound healing, mice were separated into 4 groups. Mice in Group I were not treated with IPL, whereas, dorsal skins of mice in Groups II, III, and IV were treated with 35 J/cm2, 25 J/cm2, and 15 J/cm2 IPL, respectively. After 2 weeks, dorsal island skin flaps were raised, based on the left deep circumflex iliac vessels as pedicles; then, survival rate was assessed. Flaps in Group IV (treated with lowest dose of IPL have a survival rate significantly higher than other groups. Counting blood vessels did not demonstrate any significant differences; however, vessel dilation was found in this group. The results show that IPL at the therapeutic doses which are usually applied to humans is harmful to mouse dorsal skin and did not enhance wound healing, whereas, IPL at much lower dose could improve wound healing. The possible mechanism is the dilation of tissue vasculature thanks to the electromagnetic character of IPL. Another mechanism could be the heat-shock protein production.

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

    OpenAIRE

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

    2011-01-01

    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 enh...

  6. Early changes produced in mouse skin by the application of three middle distillates.

    Science.gov (United States)

    Grasso, P; Sharratt, M; Ingram, A J

    1988-01-01

    It has been reported by the American Petroleum Institute (API) that dermal applications of certain middle distillates of mineral oils can result in high incidences of skin tumours in mice. This was unexpected as the polycyclic aromatic hydrocarbon (PAH) levels in these were below detection limits. To examine the possible role of tissue injury in the induction of tumours, the skin reactions produced by thrice weekly applications of three middle distillates similar to those tested by the API were examined grossly and histopathologically at intervals up to 6 weeks. Various reference materials and oils were used as controls. Preliminary histological examination showed that severe skin damage was present from week 1 onwards in mice treated with the three middle distillates, two of them producing epidermal loss and ulceration. Marked epidermal hyperplasia was produced by all three middle distillates. These findings support the view that regenerative epidermal hyperplasia due to repeated severe skin damage may have exerted a powerful promotional effect in the production of the skin tumours by middle distillates in the API study. PMID:3180034

  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. Skin.

    Science.gov (United States)

    Mancini, Anthony J

    2004-04-01

    Human skin provides a barrier between the host and the physical, chemical, and biological environment. It is also a potential portal of entry for hazardous or infectious agents and a potential target of environmental toxins. Cutaneous vulnerability may take on many forms in the embryo, infant, child, and adolescent. Teratogenic agents may occasionally target skin, as appreciated in the proposed association of the antithyroid medication methimazole, with the congenital malformation known as aplasia cutis congenita. Percutaneous absorption of topically applied substances and the potential for resultant drug toxicities are important considerations in the child. Many topical agents have been associated with systemic toxicity, including alcohol, hexachlorophene, iodine-containing compounds, eutectic mixture of local anesthetics, and lindane. Percutaneous toxicity is of greatest concern in the premature infant, in whom immaturity of the epidermal permeability barrier results in disproportionately increased absorption. Immature drug metabolism capabilities may further contribute to the increased risk in this population. Ultraviolet (UV) radiation exposure, which increases an individual's risk of cutaneous carcinogenesis, may be a particularly significant risk factor when it occurs during childhood. The "critical period hypothesis" suggests that UV exposure early in life increases the risk of eventual development of malignant melanoma. Other risk factors for malignant melanoma may include severe sunburns during childhood, intense intermittent UV exposure, and increased susceptibility of pediatric melanocytes to UV-induced DNA damage. Last, percutaneous exposure to environmental toxins and chemicals, such as insecticides and polychlorinated biphenyls, may differ between children and adults for several reasons, including behavioral patterns, anatomic and physiologic variations, and developmental differences of vital organs. PMID:15060207

  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-stag...

  10. 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

    2016-01-01

    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. PMID:27077818

  11. 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...

  12. 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.

  13. Genetically engineered mouse models for skin research: taking the next step

    OpenAIRE

    Chen, Jiang; Roop, Dennis R.

    2008-01-01

    Genetically engineered mouse models are invaluable to investigators in nearly all areas of biomedical research. The use of genetically engineered mice has allowed researchers to explore fundamental functions of genes in a mammal that shares substantial similarities with human physiology and pathology. Genetically engineered mice are often used as animal models of human diseases that are vital tools in investigating disease development and in developing and testing novel therapies. Gene target...

  14. Inhibition of DMBA/croton oil-induced two-stage mouse skin carcinogenesis by diphenylmethyl selenocyanate.

    Science.gov (United States)

    Das, R K; Ghosh, S; Sengupta, A; Das, S; Bhattacharya, S

    2004-10-01

    Selenium, an essential micronutrient, is associated with antioxidant functions, physiological defence mechanisms against different diseases including several types of cancers. Search for new selenium compounds with more chemopreventive activities and lesser toxicities are in progress. In the present study, the antioxidative roles of a synthetic organoselenium compound, diphenylmethyl selenocyanate, were evaluated against 7,12-dimethylbenz(a)anthracene (DMBA)/croton oil-induced two-stage mouse skin carcinogenesis model. The compound was administered orally in carcinogen-induced mice in two different non-toxic doses: 2 mg/kg body weight and 3 mg/kg body weight. Significant inhibition in the incidence of papilloma formation (58-80%) as well as in the cumulative number of papilloma per papilloma-bearing mouse were observed in the treated groups as compared with the carcinogen control group. The compound was also found to significantly upregulate different phase II detoxifying enzymes in liver cytosol such as glutathione-S-transferase (Pliver microsomes was significantly inhibited (P<0.05) in a dose-dependent manner by diphenylmethyl selenocyanate. Thus the compound exerts its chemopreventive activity by reducing papilloma formation during chemically induced carcinogenesis, which in turn, may be through modulating the level of lipid peroxidation and phase II detoxifying enzyme system at the doses evaluated. PMID:15452454

  15. Disruption of protein kinase Ceta results in impairment of wound healing and enhancement of tumor formation in mouse skin carcinogenesis.

    Science.gov (United States)

    Chida, Kazuhiro; Hara, Takeshi; Hirai, Takaaki; Konishi, Chieko; Nakamura, Kenji; Nakao, Kazuki; Aiba, Atsu; Katsuki, Motoya; Kuroki, Toshio

    2003-05-15

    We have generated a mouse strain lacking protein kinase C (PKC) eta to evaluate its significance in epithelial organization and tumor formation. The PKCeta-deficient mice exhibited increased susceptibility to tumor formation in two-stage skin carcinogenesis by single application of 7,12-dimethylbenz(a)anthracene (DMBA) for tumor initiation and repeated applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) for tumor promotion. The tumor formation was not enhanced by DMBA or TPA treatment alone, suggesting that PKCeta suppresses tumor promotion. Epidermal hyperplasia induced by topical TPA treatment was prolonged in the mutant mice. The enhanced tumor formation may be closely associated with the prolonged hyperplasia induced by topical TPA treatment. In the mutant mice, after inflicting injury by punch biopsy, wound healing on the dorsal skin, particularly reepithelialization, was significantly delayed and impaired in structure. Impairment of epithelial regeneration in wound healing indicates a possibility that PKCeta plays a role in maintenance of epithelial architecture. Homeostasis in epithelial tissues mediated by PKCeta is important for tumor formation in vivo. We propose that PKCeta is involved in tumor formation modulated by regulation of proliferation and remodeling of epithelial cells in vivo. PMID:12750259

  16. 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.

  17. Transcription-coupled repair: Impact on UV-induced mutagenesis in cultured rodent cells and mouse skin tumors

    International Nuclear Information System (INIS)

    UV-induced cyclobutane pyrimidine dimers (CPDs) are removed with accelerated speed from the transcribed strand of expressed genes in cultured mammalian cells by a process called transcription-coupled repair (TCR). It has been previously shown that this phenomenon has consequences for the molecular nature of the mutations induced by UV-light. Here, we review these data and show that TCR has not only a clear impact on UV-induced mutations in cultured mammalian cells but also on genes involved in tumor formation in the skin of UV-exposed mice. Mutations observed in the p53 gene in UV-induced squamous cell carcinoma are predominantly found at sites of dipyrimidines in the non-transcribed strand. In contrast, in UVC-irradiated Csb -/- Chinese hamster cells and in UVB-induced tumors in the Csb -/- mouse, almost all mutations are at positions of dipyrimidine sites in the transcribed strand of the mutated gene. Csb -/- mice appear to be susceptible to UVB-induced skin cancer in contrast to the human CSB patients. We speculate that the UVB-induced cancer susceptibility of Csb -/- mice is related to the absence of TCR as well as to a lack of a compensating global genome repair system for CPDs in mice

  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. Nitisinone improves eye and skin pigmentation defects in a mouse model of oculocutaneous albinism

    OpenAIRE

    Onojafe, Ighovie F.; Adams, David R; Simeonov, Dimitre R.; Zhang, Jun; Chan, Chi-Chao; Bernardini, Isa M.; Sergeev, Yuri V.; Dolinska, Monika B.; Alur, Ramakrishna P.; Brilliant, Murray H.; William A Gahl; Brooks, Brian P.

    2011-01-01

    Mutation of the tyrosinase gene (TYR) causes oculocutaneous albinism, type 1 (OCA1), a condition characterized by reduced skin and eye melanin pigmentation and by vision loss. The retinal pigment epithelium influences postnatal visual development. Therefore, increasing ocular pigmentation in patients with OCA1 might enhance visual function. There are 2 forms of OCA1, OCA-1A and OCA-1B. Individuals with the former lack functional tyrosinase and therefore lack melanin, while individuals with th...

  20. A polygenic mouse model of psoriasiform skin disease in CD18-deficient mice.

    OpenAIRE

    Bullard, D C; Scharffetter-Kochanek, K; McArthur, M J; Chosay, J. G.; McBride, M E; Montgomery, C A; Beaudet, A L

    1996-01-01

    Previously, a hypomorphic mutation in CD18 was generated by gene targeting, with homozygous mice displaying increased circulating neutrophil counts, defects in the response to chemically induced peritonitis, and delays in transplantation rejection. When this mutation was backcrossed onto the PL/J inbred strain, virtually all homozygous mice developed a chronic inflammatory skin disease with a mean age of onset of 11 weeks after birth. The disease was characterized by erythema, hair loss, and ...

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

    International Nuclear Information System (INIS)

    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(RD50) 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(Do) 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

  2. 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.

  3. 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.

  4. UVB irradiation-enhanced zinc oxide nanoparticles-induced DNA damage and cell death in mouse skin.

    Science.gov (United States)

    Pal, Anu; Alam, Shamshad; Mittal, Sandeep; Arjaria, Nidhi; Shankar, Jai; Kumar, Mahadeo; Singh, Dhirendra; Pandey, Alok Kumar; Ansari, Kausar Mahmood

    2016-09-01

    UV-induced reactive oxygen species (ROS) have been implicated in photocarcinogenesis and skin aging. This is because UV-induced ROS can induce DNA damage that, if unrepaired, can lead to carcinogenesis. Sunscreens contain UV attenuators, such as organic chemical and/or physical UV filters, which can prevent all forms of damage from UV irradiation. In recent years, the effective broad-spectrum UV attenuation properties of ZnO-nanoparticles (ZnO-NPs) have made them attractive as active components in sunscreens and other personal care products. As the use of ZnO-NPs in sunscreens is on the rise, so is public concern about their safety, particularly with exposure to sunlight. Therefore, in the present study, using various experimental approaches, we investigated the possible toxic effects resulting from exposure to UVB and ZnO-NPs in primary mouse keratinocytes (PMKs) as well as in the skin of SKH-1 hairless mice. The findings of the present study demonstrated that co-exposure to UVB and ZnO-NPs: (1) translocated the ZnO-NPs into the nucleus of PMKs; (2) caused enhanced generation of ROS; (3) induced more severe DNA damage as evident by alkaline comet assay and immunocytochemistry for γ-H2AX and 8-hydroxy-2'-deoxyguanosine (8-OHdG); and (4) subsequently caused much more pronounced cell death in PMKs. Further, to elucidate the physiological relevance of these in vitro findings, SKH-1 hairless mice were topically treated with ZnO-NPs and after 30min irradiated with UVB (50mJ/cm(2)). Interestingly, we found that co-exposure of ZnO-NPs and UVB caused increased oxidative DNA damage and cell death, indicated by immunostaining for 8-OHdG and TUNEL assay in sections of exposed mouse skin. Thus, collectively, our findings suggest that UVB exposure increases ZnO-NPs-mediated oxidative stress and oxidative damage, thereby enhancing ZnO-NPs-induced cell death. PMID:27542711

  5. Oncostatin M overexpression induces skin inflammation but is not required in the mouse model of imiquimod-induced psoriasis-like inflammation.

    Science.gov (United States)

    Pohin, Mathilde; Guesdon, William; Mekouo, Adela Andrine Tagne; Rabeony, Hanitriniaina; Paris, Isabelle; Atanassov, Hristo; Favot, Laure; Mcheik, Jiad; Bernard, François-Xavier; Richards, Carl D; Amiaud, Jérôme; Blanchard, Frédéric; Lecron, Jean-Claude; Morel, Franck; Jégou, Jean-François

    2016-07-01

    Oncostatin M (OSM) has been reported to be overexpressed in psoriasis skin lesions and to exert proinflammatory effects in vitro on human keratinocytes. Here, we report the proinflammatory role of OSM in vivo in a mouse model of skin inflammation induced by intradermal injection of murine OSM-encoding adenovirus (AdOSM) and compare with that induced by IL-6 injection. Here, we show that OSM potently regulates the expression of genes involved in skin inflammation and epidermal differentiation in murine primary keratinocytes. In vivo, intradermal injection of AdOSM in mouse ears provoked robust skin inflammation with epidermal thickening and keratinocyte proliferation, while minimal effect was observed after AdIL-6 injection. OSM overexpression in the skin increased the expression of the S100A8/9 antimicrobial peptides, CXCL3, CCL2, CCL5, CCL20, and Th1/Th2 cytokines, in correlation with neutrophil and macrophage infiltration. In contrast, OSM downregulated the expression of epidermal differentiation genes, such as cytokeratin-10 or filaggrin. Collectively, these results support the proinflammatory role of OSM when it is overexpressed in the skin. However, OSM expression was not required in the murine model of psoriasis induced by topical application of imiquimod, as demonstrated by the inflammatory phenotype of OSM-deficient mice or wild-type mice treated with anti-OSM antibodies. PMID:27122058

  6. 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.

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

    Science.gov (United States)

    Yoshida, Shohei; Lee, Jong O; Nakamura, Kiwamu; Suzuki, Sumihiro; Hendon, David N; Kobayashi, Makiko; Suzuki, Fujio

    2014-01-01

    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. PMID:24497916

  8. 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.

  9. Recombinant Goat VEGF164 Increases Hair Growth by Painting Process on the Skin of Shaved Mouse.

    Science.gov (United States)

    Bao, Wenlei; Yin, Jianxin; Liang, Yan; Guo, Zhixin; Wang, Yanfeng; Liu, Dongjun; Wang, Xiao; Wang, Zhigang

    2014-09-01

    To detect goat vascular endothelial growth factor (VEGF)-mediated regrowth of hair, full-length VEGF164 cDNA was cloned from Inner Mongolia cashmere goat (Capra hircus) into the pET-his prokaryotic expression vector, and the recombinant plasmid was transferred into E. coli BL21 cells. The expression of recombinant 6×his-gVEGF164 protein was induced by 0.5 mM isopropyl thio-β-D-galactoside at 32°C. Recombinant goat VEGF164 (rgVEGF164) was purified and identi ed by western blot using monoclonal anti-his and anti-VEGF antibodies. The rgVEGF164 was smeared onto the dorsal area of a shaved mouse, and we noted that hair regrowth in this area was faster than in the control group. Thus, rgVEGF164 increases hair growth in mice. PMID:25178380

  10. Modulatory influence of Rosemarinus officinalis on DMBA-induced mouse skin tumorigenesis.

    Science.gov (United States)

    Sancheti, Garima; Goyal, Pk

    2006-01-01

    The present investigation was undertaken to explore the anti-tumor promoting activity of Rosemarinus officinalis on two-stage skin carcinogenesis, induced by a single topical application of 7, 12-dimethylbenz(a)anthracene and promoted by treatment of croton oil for 15 weeks in Swiss albino mice. Oral administration of Rosemary leaf extract at a dose of 1,000 mg/ kg b. wt. / day at pre, peri and post-initiational phases, was found to be effective in decreasing the tumor incidence (50, 41.7, 58.3%, respectively) in comparison to the control (100%). Furthermore, the cumulative number of papillomas, tumor yield and tumor burden were also found to be reduced in R. officinalis-treated animals. This was associated with significant alteration in liver lipid peroxidation and glutathione (GSH) levels. PMID:16839234

  11. 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

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

    International Nuclear Information System (INIS)

    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/m2/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/m2/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

  13. 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.

  14. 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.

  15. Attenuation of DMBA/croton oil induced mouse skin papilloma by Apodytes dimidiata mediated by its antioxidant and antimutagenic potential.

    Science.gov (United States)

    Divya, Menon K; Salini, Sasidharan; Meera, Nair; Lincy, Lawrence; Seema, Menon; Raghavamenon, Achuthan C; Babu, Thekkekara D

    2016-09-01

    Context Considering the role of cellular oxidative stress in mutations and subsequent transformation, phytochemicals with antioxidant potential has become a primary choice as chemopreventives. Apodytes dimidiata E. Mey. Ex. Arn (Icacinaceae), a widely used plant in Zulu traditional medicine, is reported to possess antioxidant activity. Objective To investigate the chemopreventive efficacy of methanol extract of A. dimidiata leaf (AMF). Materials and methods Antimutagenic potential of AMF (25, 50 and 75 μg/plate) was evaluated by the Ames test. The ability of AMF (100 and 250 mg/kg orally) on restoration of depleted antioxidant status by sodium fluoride (NaF) was analysed on BALB/c mice. 7,12-Dimethylbenz[a]anthracene/croton oil induced mouse skin papilloma model was studied up to 20 weeks to analyse the anticarcinogenic effect of AMF (1%, 3% and 5% topically, twice weekly for 6 weeks). Phytochemicals of AMF were characterized by GC-MS. Results AMF (75 μg/plate) reverted 4-nitro-o-phenylenediamine (NPDA) induced mutations in Salmonella typhimurium strains, TA 98, 100 and 102 by 74.8%, 72.5% and 69.3%, respectively. Against sodium azide, the percentage reversion was 80.4, 71.3 and 71.3. In mice, AMF (250 mg/kg for 4 days) increased the serum superoxide dismutase (SOD) and catalase activities by 48.71% and 30.3% against the NaF-induced drop. GSH level was improved by 48.59% with a concomitant decrease in TBARS (57.67%). The skin papilloma reduction was 79.32% for 5% AMF. Squalene, dodecanoic, tetradecanoic and hexadecanoic acids are the known antioxidant and chemopreventive molecules identified by GC-MS. Discussion and conclusion Antioxidant and antimutagenic activities of AMF might have contributed to its anticarcinogenic potential. PMID:26878464

  16. 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.

  17. Nitisinone improves eye and skin pigmentation defects in a mouse model of oculocutaneous albinism.

    Science.gov (United States)

    Onojafe, Ighovie F; Adams, David R; Simeonov, Dimitre R; Zhang, Jun; Chan, Chi-Chao; Bernardini, Isa M; Sergeev, Yuri V; Dolinska, Monika B; Alur, Ramakrishna P; Brilliant, Murray H; Gahl, William A; Brooks, Brian P

    2011-10-01

    Mutation of the tyrosinase gene (TYR) causes oculocutaneous albinism, type 1 (OCA1), a condition characterized by reduced skin and eye melanin pigmentation and by vision loss. The retinal pigment epithelium influences postnatal visual development. Therefore, increasing ocular pigmentation in patients with OCA1 might enhance visual function. There are 2 forms of OCA1, OCA-1A and OCA-1B. Individuals with the former lack functional tyrosinase and therefore lack melanin, while individuals with the latter produce some melanin. We hypothesized that increasing plasma tyrosine concentrations using nitisinone, an FDA-approved inhibitor of tyrosine degradation, could stabilize tyrosinase and improve pigmentation in individuals with OCA1. Here, we tested this hypothesis in mice homozygous for either the Tyrc-2J null allele or the Tyrc-h allele, which model OCA-1A and OCA-1B, respectively. Only nitisinone-treated Tyrc-h/c-h mice manifested increased pigmentation in their fur and irides and had more pigmented melanosomes. High levels of tyrosine improved the stability and enzymatic function of the Tyrc-h protein and also increased overall melanin levels in melanocytes from a human with OCA-1B. These results suggest that the use of nitisinone in OCA-1B patients could improve their pigmentation and potentially ameliorate vision loss. PMID:21968110

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Assessment of the potential skin irritation of lysine-derivative anionic surfactants using mouse fibroblast and human keratinocytes as an alternative to animal testing

    OpenAIRE

    Sánchez Molina, Lourdes; Mitjans Arnal, Montserrat; Infante Martínez-Pardo, Ma. Rosa; Vinardell Martínez-Hidalgo, Ma. Pilar

    2004-01-01

    Purpose. The aim of this study was to identify new surfactants with low skin irritant properties for use in pharmaceutical and cosmetic formulations, employing cell culture as an alternative method to in vivo testing. In addition, we sought to establish whether potential cytotoxic properties were related to the size of the counterions bound to the surfactants. Methods. Cytotoxicity was assessed in the mouse fibroblast cell line 3T6, and the human keratinocyte cell line NCTC 2544, using the MT...

  3. 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.

  4. The radiation effect on healing of surgical wound in mouse skin

    International Nuclear Information System (INIS)

    Remarkable improvement in control of malignant tumor was achieved by combined surgery and post-operative radiation therapy. In past, radiation therapy had been recommended after 4-6 weeks from operation because of worry about increased complication rate of surgical wound by post-operative irradiation. Nowadays, early surgical extirpation and early post-operative irradiation is recommended for better therapeutic effect. To evaluate the relationship between surgery-radiation interval and healing of surgical wound, an experimental study was undertaken using a total of 132 mice. A single dose of 2000 rads irradiation was delivered immediate after and on 1, 3, 5, 10, 14 days after incision and suture on the skin of hind limbs of mice. Tensile strengths of the wounds were measured after removal of stitches on 1st, 3rd, 5th, 7th, 10th, 14th and 21st post-operative days. The results are summarized as follows: 1. Wound healing was delayed by irradiation delivered within 3 days from operation. 2. No significant delay of wound healing was observed by irradiation on 5 or more days after operation. 3. Normal wound strength was attained at 21st post-operative day in any surgery-radiation interval. 4. More severe delay of wound healing by irradiation at 24 hrs after operation than by immediate post-operative irradiation although statistical significance is not confirmed. In conclusion, early post-operative irradiation delays healing of the surgical wound though ultimately tensile strength reaches the value of non-irradiated wound

  5. 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.

  6. Effect of topical application of antioxidants and free radical scavengers on protection of hairless mouse skin exposed to chronic doses of ultraviolet B

    International Nuclear Information System (INIS)

    treatment, respectively. Conclusion: Data from these studies suggest that low level chronic exposures to UV can lead to alteration of the skin, like epidermal thickening and appearance of sunburn cells. The data also indicates that a mix of common antioxidants and free radical scavengers are photoprotective against chronic skin damage in the hairless mouse skin model. (au)

  7. Effect of topical application of antioxidants and free radical scavengers on protection of hairless mouse skin exposed to chronic doses of ultraviolet B

    Energy Technology Data Exchange (ETDEWEB)

    Muizzuddin, N.; Shakoori, A.R. [Univ. of the Punjab, Dept. of Zoology, Cell and Molecular Biology Lab., Lahore (Pakistan); Marenus, K.D. [SUNY at Stonybrook, Stonybrook, NY (United States)

    1998-11-01

    treatment, respectively. Conclusion: Data from these studies suggest that low level chronic exposures to UV can lead to alteration of the skin, like epidermal thickening and appearance of sunburn cells. The data also indicates that a mix of common antioxidants and free radical scavengers are photoprotective against chronic skin damage in the hairless mouse skin model. (au)

  8. Photosensitivity of murine skin greatly depends on the genetic background: clinically relevant dose as a new measure to replace minimal erythema dose in mouse studies.

    Science.gov (United States)

    Gyöngyösi, Nóra; Lőrincz, Kende; Keszeg, András; Haluszka, Dóra; Bánvölgyi, András; Tátrai, Erika; Kárpáti, Sarolta; Wikonkál, Norbert M

    2016-07-01

    Artificial UV irradiation of murine skin is a frequently used method for testing photosensitivity, study carcinogenesis and photoprotective effects of different compounds. However, doses of UV radiation and mouse strains used in experiments vary greatly. The genetic background of mice may influence the photosensitivity as melanin content, pigmentation and hair cycle parameters are dissimilar. Doses of UV are often expressed in relation to the minimal erythema dose (MED) that was not necessarily determined for the given strain. We set out to standardize the method of measuring photosensitivity in three commonly used mouse strains, C57BL/6N, Balb/c and SKH-1. We found that MED may not be determined for some strains as erythema development in mice with diverse genotypes differs greatly. We measured the oedema response in vivo and ex vivo by using OCT. Given the strain-specific variability of erythema, we introduced Clinically Relevant Dose (CRD) as a new term to replace MED in experiments, to describe the lowest dose that triggers a perceptible skin reaction in mice. Not only the CRD but the proportion of erythema and oedema were different in strains examined. C57BL/6N mice display skin reactions at the lowest UVB dose, while SKH-1 hairless mice show changes, mostly oedema, after higher doses of UVB. The cellular composition and skin thickness were examined by histopathology. IL-1beta and IL-6 levels in skin correlated with the increasing doses of UVB. Despite the variations in the degree of erythema and oedema, no major differences in cytokine expressions were seen among various strains of mice. PMID:26910301

  9. Ultrasonic stimulation of mouse skin reverses the healing delays in diabetes and aging by activation of Rac1

    OpenAIRE

    Roper, James A.; Williamson, Rosalind C.; Bally, Blandine; Cowell, Christopher AM; Brooks, Rebecca; Stephens, Phil; Harrison, Andrew J; Bass, Mark D.

    2015-01-01

    Chronic skin healing defects are one of the leading challenges to lifelong wellbeing, affecting 2-5% of populations. Chronic wound formation is linked to age and diabetes and frequently leads to major limb amputation. Here we identify a strategy to reverse fibroblast senescence and improve healing rates. In healthy skin, fibronectin activates Rac1 in fibroblasts, causing migration into the wound bed and driving wound contraction. We discover that mechanical stimulation of skin with ultrasound...

  10. Gross and microscopic lesions in the female SENCAR mouse skin and lung in tumor initiation and promotion studies.

    OpenAIRE

    Knutsen, G L; Kovatch, R M; Robinson, M.

    1986-01-01

    The skin and lung tissues from SENCAR mice used as part of the Environmental Protection Agency's (EPA's) Carcinogenesis Testing Matrix were examined. This study included SENCAR mice used in three different short-term bioassay protocols in which the skin papilloma assay was used to identify initiators, promoters, and complete carcinogens. Also included were the pathology findings from SENCAR mice used in the combined bioassay in which the skin assay and the lung adenoma assay were conducted si...

  11. 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.

  12. 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.

  13. Human atopic dermatitis skin-derived T cells can induce a reaction in mouse keratinocytes in vivo

    DEFF Research Database (Denmark)

    Martel, Britta C; Blom, Lars; Dyring-Andersen, Beatrice;

    2015-01-01

    through keratinocyte activation and consequently cause development of eczematous lesions. Punch biopsies of lesional skin from AD patients were used to establish skin-derived T cell cultures and which were transferred into NOD.Cg-Prkd(scid) Il2rg(tm1Sug) /JicTac (NOG) mice. We found that subcutaneous...

  14. 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.

  15. 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. PMID:22363217

  16. 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.

  17. 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.

  18. 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

  19. The risk of hydroquinone and sunscreen over-absorption via photodamaged skin is not greater in senescent skin as compared to young skin: nude mouse as an animal model.

    Science.gov (United States)

    Hung, Chi-Feng; Chen, Wei-Yu; Aljuffali, Ibrahim A; Shih, Hui-Chi; Fang, Jia-You

    2014-08-25

    Intrinsic aging and photoaging modify skin structure and components, which subsequently change percutaneous absorption of topically applied permeants. The purpose of this study was to systematically evaluate drug/sunscreen permeation via young and senescent skin irradiated by ultraviolet (UV) light. Both young and senescent nude mice were subjected to UVA (10 J/cm(2)) and/or UVB radiation (175 mJ/cm(2)). Physiological parameters, immunohistology, and immunoblotting were employed to examine the aged skin. Hydroquinone and sunscreen permeation was determined by in vitro Franz cell. In vivo skin absorption was documented using a hydrophilic dye, rhodamine 123 (log P=-0.4), as a permeant. UVA exposure induced cyclooxygenase (COX)-2 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) upregulation. Epidermal tight junction (TJ) were degraded by UVA. UVB increased transepidermal water loss (TEWL) from 13 to 24 g/m(2)/h. Hyperplasia and inflammation, but not loss of TJ, were also observed in UVB-treated skin. UVA+UVB- and UVA-irradiated skin demonstrated similar changes in histology and biomarkers. UVA+UVB or UVA exposure increased hydroquinone flux five-fold. A negligible alteration of hydroquinone permeation was shown with UVB exposure. Hydroquinone exhibited a lower penetration through senescent skin than young skin. Both UVA and UVB produced enhancement of oxybenzone flux and skin uptake. However, the amount of increase was less than that of hydroquinone delivery. Photoaging did not augment skin absorption of sunscreens with higher lipophilicity, including avobenzone and ZnO. Exposure to UVA generally increased follicular entrance of these permeants, which showed two- to three-fold greater follicular uptake compared to the untreated group. Photoaging had less impact on drug/sunscreen absorption with more lipophilic permeants. Percutaneous absorption did not increase in skin subjected to both intrinsic and extrinsic aging. PMID:24858384

  20. 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.

  1. 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.

  2. 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. PMID:26335024

  3. A Herbal Formula, Atofreellage, Ameliorates Atopic Dermatitis-Like Skin Lesions in an NC/Nga Mouse Model.

    Science.gov (United States)

    Kim, Won-Yong; Kim, Hyeong-Geug; Lee, Hye-Won; Lee, Jin-Seok; Im, Hwi-Jin; Kim, Hyo-Seon; Lee, Sung-Bae; Son, Chang-Gue

    2015-01-01

    We evaluated the anti-atopic dermatitis (AD) effect of Atofreellage (AF), a herbal formula composed of 10 medicinal plants. AD was induced on the dorsal skin areas of NC/Nga mice (male, seven weeks old) by daily application of 2,4-dinitrochlorobenzene (DNCB) for five weeks. After three weeks of DNCB application, 200 μL of AF (0, 25, 50 or 100 mg/mL) was applied to the skin lesions. Histological findings, blood cell populations, serum levels of immunoglobulin E (IgE), histamine, pro-inflammatory cytokines, and inflammatory signaling in the skin tissue, and T-helper cell type 2 (Th₂)-related cytokines in splenocytes were analyzed. Histopathological findings showed AF treatment notably attenuated the thickness of dorsal skin, and eosinophil infiltration. AF treatment (especially 100 mg/mL) also demonstrably ameliorated the blood cell population abnormalities, as the notable elevation of serum concentrations of IgE, histamine, TNF-α, IL-6 and IL-1β were remarkably normalized by AF treatment. Western blot analysis evidenced the apparent normalization of inflammatory signals (ERK, p38 MAP kinase, JNK, and NF-κB) in the skin tissue. Additionally, AF treatment notably attenuated the activation of Th₂-dominant cytokines (IL-13, IL-4, and IL-5) in Con A-treated splenocytes in an ex vivo assay. In conclusion, this study provides experimental evidence for the clinical relevance of Atofreellage. PMID:26712731

  4. 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.

  5. 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.

  6. 小鼠对量子点的透皮吸收和代谢%Transdermal Delivery Through in vivo Mouse Skin and Metabolic Path of Quantum Dots

    Institute of Scientific and Technical Information of China (English)

    唐蕾; 张春玲; 宋光明; 徐忠伟; 金迅

    2012-01-01

    皮肤是身体的最大器官,能够直接与含纳米材料的防晒霜、化妆品等接触,但是人们对纳米材料的皮肤渗透性却了解不多.本文研究了水溶性硫硒化镉(CdSeS)量子点纳米颗粒的皮肤渗透性和在体内的代谢情况.将雄性ICR鼠背部脱毛,在脱毛部位涂抹直径约为5nm、发光波长为620 nm的量子点0.32 nmol,然后检测皮肤和心、肝、脾、肺、肾中量子点沉积量随时间的变化情况.荧光显微像显示,量子点能够堆积在皮肤的表皮层中和真皮层的毛囊和腺体中,电感耦合等离子体质谱(inductively coupled plasma-mass spectrometry,ICP-MS)结果表明,透皮吸收的量子点能够沉积在器官中,并且肝和肾中沉积的量子点代谢缓慢,涂抹量子点5天之后,肾脏中残存的镉离子浓度仍超过14 ng/g.这些结果表明,量子点能够被小鼠透皮吸收,而且对肝和肾产生严重影响.%Skin is the largest organ of the body and is a potential route of exposure to sunscreens and cosmetics containing nanoparticles, but the permeability of the skin to these nanoparticles is unknown. In this paper, we studied the transdermal delivery capacity through mouse skin of water-soluble CdSeS quantum dots (QDs) and the deposition of these QDs in the body. QD solution was coated on the dorsal hairless skin of male ICR mice. Fluorescence microscope was used to observe the deposition of QDs in mouse skin and heart, liver, spleen, lung and kidney. Inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure the mCd concentration to indicate the concentration of QDs in plasma and organs. The fluorescence images show that QDs can penetrate into the dermal layer and deposit in the organs through blood circulation. ICP-MS result indicates that QDs deposit seriously in liver and kidney, and they are difficult to clear. 111Cd concentration is still more than 14 ng/g in kidney after 5 days. These results suggest that QDs has in vivo

  7. Diminution of acute radiation reaction of mouse skin with low-intensity infrared laser/red diodes-emitted light

    International Nuclear Information System (INIS)

    Efficiency of the application of different regimes of laser treatment of radiation-induced skin reactions in mice feet is compared. Posterior limb feet of mice were exposed to acute X radiation at 30-36 Gy dose or fractionated radiation at 45 Gy dose. In the day of primary irradiation or different time later the feet were treated using magnetic infrared laser therapeutic MILTA-01 apparatus. Magnetic and light components of the MILTA-01 apparatus reduce the effect of radiation on mice skin corresponding two time decrease in X-radiation dose

  8. 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.

  9. 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

    2016-01-01

    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. PMID:27347933

  10. 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.

  11. Dual Effects of Bisphosphonates on Ectopic Skin and Vascular Soft Tissue Mineralization versus Bone Microarchitecture in a Mouse Model of Generalized Arterial Calcification of Infancy.

    Science.gov (United States)

    Li, Qiaoli; Kingman, Joshua; Sundberg, John P; Levine, Michael A; Uitto, Jouni

    2016-01-01

    Generalized arterial calcification of infancy is an intractable ectopic mineralization disorder caused by mutations in the ENPP1 gene, resulting in reduced plasma inorganic pyrophosphate (PPi) levels. We previously characterized the Enpp1(asj) mutant mouse as a model of generalized arterial calcification of infancy, and we have now explored the potential efficacy of bisphosphonates, nonhydrolyzable PPi analogs, in preventing ectopic mineralization in these mice. The mice were maintained on either basic diet (control) or diets containing etidronate or alendronate in three different concentrations (experimental). Considering low bioavailability of bisphosphonates when administered orally, subsequent studies tested the mice with subcutaneous injections of etidronate. The treatments were initiated at 4 weeks of age, and the degree of mineralization was assessed at 12 weeks of age by quantitation of calcium deposits in the muzzle skin containing dermal sheath of vibrissae and in aorta. We found that bisphosphonate treatments significantly reduced mineralization in skin and aorta. These changes in treated mice were accompanied with restoration of their bone microarchitecture, determined by microcomputed tomography. The inhibitory capacity of bisphosphonates, with mechanistic implications, was confirmed in a cell-based mineralization assay in vitro. Collectively, these results suggest that bisphosphonate treatment may be beneficial by a dual effect for preventing ectopic soft tissue mineralization while correcting decreased bone mineralization in generalized arterial calcification of infancy caused by ENPP1 mutations. PMID:26763447

  12. Designing a ridge filter based on a mouse foot skin reaction to spread out Bragg-peaks for carbon-ion radiotherapy

    International Nuclear Information System (INIS)

    Background and purpose: Carbon-ion radiotherapy uses spread-out Bragg peaks (SOBP) to produce uniform biological effects within a target volume. The relative biological effectiveness is determined by the in vitro cell kill after a single dose is employed to design the SOBP. A question remains as to whether biological effects for in vivo tissues after fractionated doses are also uniform within the SOBP. Material and methods: Mouse foot skin was irradiated with fractionated doses of carbon ions at various linear energy transfer (LET) values. A new ridge filter was designed based on alpha and beta values for each LET to cause moderate skin reaction, and was studied concerning its uniformity. Results: The reciprocal total doses of intermediate-LET carbon ions and of reference gamma rays linearly increased with an increase of a dose per fraction in Fe-plots. As the single total dose of higher LET run off linearity, data obtained from 2 to 6 fractions were used to design a new ridge filter. The physical dose distribution of the new ridge filter was almost identical to, and indistinguishable from, the ridge filter designed based on the in vitro cell kill. Conclusions: The LET dependence of alpha is a principle of the biological factor to be used for designing spread-out Bragg peaks of carbon-ion radiotherapy

  13. 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.

  14. The Immune Response to Skin Trauma Is Dependent on the Etiology of Injury in a Mouse Model of Burn and Excision.

    Science.gov (United States)

    Valvis, Samantha M; Waithman, Jason; Wood, Fiona M; Fear, Mark W; Fear, Vanessa S

    2015-08-01

    Skin trauma has many different causes including incision, blunt force, and burn. All of these traumas trigger an immune response. However, it is currently unclear whether the immune response is specific to the etiology of the injury. This study was established to determine whether the immune response to excision and burn injury of equivalent extent was the same. Using a mouse model of a full-thickness 19 mm diameter excision or 19 mm diameter full-thickness burn injury, we examined the innate immune response at the level of serum cytokine induction, whole-blood lymphocyte populations, dendritic cell function/phenotype, and the ensuing adaptive immune responses of CD4 and CD8 T-cell populations. Strikingly, both the innate and adaptive immune system responses differed between the burn and excision injuries. Acute cytokine induction was faster and different in profile to that of excision injury, leading to changes in systemic monocyte and neutrophil levels. Differences in the immune profile between burn and excision were also noted up to day 84 post injury, suggesting that the etiology of injury leads to sustained changes in the response. This may in part underlie clinical observations of differences in patient morbidity and mortality in response to different skin injury types. PMID:25826422

  15. Mouse skin tumor initiation-promotion and complete carcinogenesis bioassays: mechanisms and biological activities of emission samples.

    OpenAIRE

    Nesnow, S; Triplett, L L; Slaga, T J

    1983-01-01

    Extracts of soots obtained from various sources were applied to the skin of mice in an effort to identify carcinogens in these mixtures and to link these materials to the etiology of human cancer. Samples of coal chimney soot, coke oven materials, industrial carbon black, oil shale soot, and gasoline vehicle exhaust materials have been examined by this method. The studies reported here have been constructed to compare the carcinogenic and tumorigenic potency of extracts from various particula...

  16. Flat Mount Imaging of Mouse Skin and Its Application to the Analysis of Hair Follicle Patterning and Sensory Axon Morphology

    OpenAIRE

    Chang, Hao; Wang, Yanshu; Wu, Hao; Nathans, Jeremy

    2014-01-01

    Skin is a highly heterogeneous tissue. Intra-dermal structures include hair follicles, arrector pili muscles, epidermal specializations (such as Merkel cell clusters), sebaceous glands, nerves and nerve endings, and capillaries. The spatial arrangement of these structures is tightly controlled on a microscopic scale - as seen, for example, in the orderly arrangement of cell types within a single hair follicle - and on a macroscopic scale - as seen by the nearly identical orientations of thous...

  17. 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.

  18. 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. PMID:27203461

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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. PMID:24940652

  5. 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.

  6. 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.

  7. Curcumin Protects against UVB-Induced Skin Cancers in SKH-1 Hairless Mouse: Analysis of Early Molecular Markers in Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Kuen-Daw Tsai

    2012-01-01

    Full Text Available Curcumin (CUR has been shown to possess a preventive effect against various cancers and interfere with multiple-cell signaling pathways. We evaluated the protective effects of CUR in regression of UVB-induced skin tumor formation in SKH-1 hairless mice and its underlying early molecular biomarkers associated with carcinogenesis. Mice irradiated with UVB at 180 mJ/cm2 twice per week elicited 100% tumor incidence at 20 weeks. Topical application of CUR prior to UVB irradiation caused delay in tumor appearance, multiplicity, and size. Topical application of CUR prior to and immediately after a single UVB irradiation (180 mJ/cm2 resulted in a significant decrease in UVB-induced thymine dimer-positive cells, expression of proliferative cell nuclear antigen (PCNA, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and apoptotic sunburn cells together with an increase in p53 and p21/Cip1-positive cell population in epidermis. Simultaneously, CUR also significantly inhibited NF-κB, cyclooxygenase-2 (COX-2, prostaglandin E2 (PGE2, and nitric oxide (NO levels. The results suggest that the protective effect of CUR against photocarcinogenesis is accompanied by downregulation of cell proliferative controls, involving thymine dimer, PCNA, apoptosis, transcription factors NF-κB, and of inflammatory responses involving COX-2, PGE2, and NO, while upregulation of p53 and p21/Cip1 to prevent DNA damage and facilitate DNA repair.

  8. Radionecrosis skin model induced an athymic mouse nude (Nu/Nu) for development of dermal-epidermal human substitute based regenerative therapy

    International Nuclear Information System (INIS)

    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)

  9. 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.

  10. Bromelain nanoparticles protect against 7,12-dimethylbenz[a]anthracene induced skin carcinogenesis in mouse model.

    Science.gov (United States)

    Bhatnagar, Priyanka; Pant, Aditya B; Shukla, Yogeshwer; Chaudhari, Bhushan; Kumar, Pradeep; Gupta, Kailash C

    2015-04-01

    Conventional cancer chemotherapy leads to severe side effects, which limits its use. Nanoparticles (NPs) based delivery systems offer an effective alternative. Several evidences highlight the importance of Bromelain (BL), a proteolytic enzyme, as an anti-tumor agent which however has been limited due to the requirement of high doses at the tumor site. Therefore, we illustrate the development of BL loaded poly (lactic-co-glycolic acid) NPs that show enhanced anti-tumor effects compared to free BL. The formulated NPs with a mean particle size of 130.4 ± 8.81 nm exhibited sustained release of BL. Subsequent investigation revealed enhanced anti-tumor ability of NPs in 2-stage skin tumorigenesis mice model. Reduction in average number of tumors (∼ 2.3 folds), delay in tumorigenesis (∼ 2 weeks), percent tumorigenesis (∼ 4 folds), and percent mortality rate as well as a reduction in the average tumor volume (∼ 2.5 folds) in mice as compared to free BL were observed. The NPs were found to be superior in exerting chemopreventive effects over chemotherapeutic effects at 10 fold reduced dose than free BL, validated by the enhanced ability of NPs (∼ 1.8 folds) to protect the DNA from induced damage. The effects were also supported by histopathological evaluations. NPs were also capable of modulating the expression of pro-apoptotic (P53, Bax) and anti-apoptotic (Bcl2) proteins. Therefore, our findings demonstrate that developed NPs formulation could be used to improve the efficacy of chemotherapy by exerting chemo-preventive effects against induced carcinogenesis at lower dosages. PMID:25619920

  11. Treatment of green tea polyphenols in hydrophilic cream prevents UVB-induced oxidation of lipids and proteins, depletion of antioxidant enzymes and phosphorylation of MAPK proteins in SKH-1 hairless mouse skin.

    Science.gov (United States)

    Vayalil, Praveen K; Elmets, Craig A; Katiyar, Santosh K

    2003-05-01

    The use of botanical supplements has received immense interest in recent years to protect human skin from adverse biological effects of solar ultraviolet (UV) radiation. The polyphenols from green tea are one of them and have been shown to prevent photocarcinogenesis in animal models but their mechanism of photoprotection is not well understood. To determine the mechanism of photoprotection in in vivo mouse model, topical treatment of polyphenols from green tea (GTP) or its most chemopreventive constituent (-)-epigallocatechin-3-gallate (EGCG) (1 mg/cm(2) skin area) in hydrophilic ointment USP before single (180 mJ/cm(2)) or multiple UVB exposures (180 mJ/cm(2), daily for 10 days) resulted in significant prevention of UVB-induced depletion of antioxidant enzymes such as glutathione peroxidase (78-100%, P 0.001). Further, to delineate the inhibition of UVB-induced oxidative stress with cell signaling pathways, treatment of EGCG to mouse skin resulted in marked inhibition of a single UVB irradiation-induced phosphorylation of ERK1/2 (16-95%), JNK (46-100%) and p38 (100%) proteins of MAPK family in a time-dependent manner. Identical photoprotective effects of EGCG or GTP were also observed against multiple UVB irradiation-induced phosphorylation of the proteins of MAPK family in vivo mouse skin. Photoprotective efficacy of GTP given in drinking water (d.w.) (0.2%, w/v) was also determined and compared with that of topical treatment of EGCG and GTP. Treatment of GTP in d.w. also significantly prevented single or multiple UVB irradiation-induced depletion of antioxidant enzymes (44-61%, P the possibility of its use for the humans, and the data obtained from this in vivo study further suggest that GTP could be useful in attenuation of solar UVB light-induced oxidative stress-mediated and MAPK-caused skin disorders in humans. PMID:12771038

  12. 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.

  13. Changes in the distribution pattern of Claudin tight junction proteins during the progression of mouse skin tumorigenesis

    International Nuclear Information System (INIS)

    epidermis) remained restricted to the cell membrane throughout the tumorigenesis protocol. However commencing 2 weeks after treatment there was a marked decrease in the number of Cldn1-positive basal cells, and the zone of Cldn1-null epidermal cells was expanded up into the lower stratified epidermis throughout the progression of DMBA/TPA treatment. In addition, there was no Cldn1 localization in the infiltrating epidermal structures of the tumorigenic epidermis. This is the first demonstration of the changes in Cldn expression in the progression of DMBA/TPA-induced skin tumors; however further investigation into the molecular mechanisms regulating the observed changes in barrier selectivity during tumorigenesis is required

  14. 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

  15. 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.

  16. Correlation of {sup 32}P-postlabelling-detection of DNA adducts in mouse skin in vivo with the polycyclic aromatic compound content and mutagenicity in Salmonella typhimurium of a range of oil products

    Energy Technology Data Exchange (ETDEWEB)

    Booth, E.D.; Loose, R.W.; Watson, W.P. [Toxicology Department, Shell International Chemicals B.V., Amsterdam (Netherlands); Brandt, H.C.A. [Product Development Department, Shell International Oil Products B.V., Amsterdam (Netherlands)

    1998-07-01

    The in vivo genotoxic activities in mouse skin of the dimethyl sulphoxide (DMSO) extracts of a range of oil products [residual aromatic extract; untreated heavy paraffinic distillate aromatic extract; mildly refined light naphthenic base oil; bitumen (vacuum residue); high viscosity index base oil obtained by catalytic hydrogenation] were evaluated by {sup 32}P-postlabelling DNA analysis. The results of quantitative {sup 32}P-postlabelling analyses of epidermal DNA from mice treated with the DMSO extracts showed linear relationships with the total polycyclic aromatic compound (PAC) contents, determined by the Institute of Petroleum method IP 346 and also the 3-6 ring PAC contents, measured by on-line liquid-liquid extraction using flow injection analysis. The {sup 32}P-postlabelling data also showed a linear relationship with the mutagenicity indices of these oil products determined in S. typhimurium TA98 using the modified Ames Salmonella microsome test. The in vivo genotoxicity of the DMSO extracts from the oil products was low, judged by {sup 32}P-postlabelling analysis of DNA adducts measured in epidermal DNA of treated mouse skin, and ranging from 2 to 723 attomole/{mu}g DNA per mg oil product. The in vivo {sup 32}P-postlabelling data from this study are consistent with these materials expressing low genotoxicity in mouse skin in vivo. The DMSO extraction procedure coupled with {sup 32}P-postlabelling DNA analysis is useful for ranking the relative genotoxic potency in vivo of a wide range of oil products. In general the trend observed is similar to rankings based on physicochemical measurements of total PAC contents or 3-6 ring PAC contents of the oil products. (orig.) With 4 figs., 1 tab., 44 refs.

  17. Correlation of 32P-postlabelling-detection of DNA adducts in mouse skin in vivo with the polycyclic aromatic compound content and mutagenicity in Salmonella typhimurium of a range of oil products

    International Nuclear Information System (INIS)

    The in vivo genotoxic activities in mouse skin of the dimethyl sulphoxide (DMSO) extracts of a range of oil products [residual aromatic extract; untreated heavy paraffinic distillate aromatic extract; mildly refined light naphthenic base oil; bitumen (vacuum residue); high viscosity index base oil obtained by catalytic hydrogenation] were evaluated by 32P-postlabelling DNA analysis. The results of quantitative 32P-postlabelling analyses of epidermal DNA from mice treated with the DMSO extracts showed linear relationships with the total polycyclic aromatic compound (PAC) contents, determined by the Institute of Petroleum method IP 346 and also the 3-6 ring PAC contents, measured by on-line liquid-liquid extraction using flow injection analysis. The 32P-postlabelling data also showed a linear relationship with the mutagenicity indices of these oil products determined in S. typhimurium TA98 using the modified Ames Salmonella microsome test. The in vivo genotoxicity of the DMSO extracts from the oil products was low, judged by 32P-postlabelling analysis of DNA adducts measured in epidermal DNA of treated mouse skin, and ranging from 2 to 723 attomole/μg DNA per mg oil product. The in vivo 32P-postlabelling data from this study are consistent with these materials expressing low genotoxicity in mouse skin in vivo. The DMSO extraction procedure coupled with 32P-postlabelling DNA analysis is useful for ranking the relative genotoxic potency in vivo of a wide range of oil products. In general the trend observed is similar to rankings based on physicochemical measurements of total PAC contents or 3-6 ring PAC contents of the oil products. (orig.)

  18. 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.

  19. 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.

  20. 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.

  1. 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. PMID:19703227

  2. Morphological classification of nuchal skin in human fetuses with trisomy 21, 18, and 13 at 12-18 weeks and in a trisomy 16 mouse.

    Science.gov (United States)

    von Kaisenberg, C S; Krenn, V; Ludwig, M; Nicolaides, K H; Brand-Saberi, B

    1998-02-01

    An increase in the nuchal translucency that can be detected at 10-14 weeks of gestation by ultrasound forms the basis for a screening test for chromosomal abnormality. Several mechanisms leading to this increase in skin thickness have been proposed, including changes of the extracellular matrix, cardiac defects and abnormalities of the large vessels. This study examines the composition of the extracellular matrix of the skin in gestational age-matched fetuses with trisomy 21, 18 and 13 from 12-18 weeks. Immunohistochemistry was applied with monoclonal and polyclonal antibodies against collagen type I, III, IV, V and VI and against laminin and fibronectin. Collagen type VI gene expression was further studied by in situ hybridization to detect differences in expression patterns of COL6A1, COL6A3 and COL1A1 between normal fetuses and those with trisomy 21. The ultrastructure of tissue samples was studied by transmission electron microscopy (TEM) and additionally by immunogold TEM. Further, we examined the morphology of the skin in an animal model for Down's syndrome, the murine trisomy 16, by light and TEM. The dermis of trisomy 21 fetuses was richer in collagen type VI than that of normal fetuses and other trisomies, and COL6A1, located on chromosome 21, was expressed in a wider area than COL6A3, which is located on chromosome 2. Collagen type I was less abundant in the skin of trisomy 18 fetuses, while the skin of all three trisomies contained a dense network of collagen type III and V in comparison with normal fetuses. Collagen type IV, of which two genes are located on chromosome 13, was expressed in the basement membranes of the skin in all fetuses and additionally in the dermal fibroblasts only of trisomy 13 fetuses. Likewise, laminin was present in all basement membranes of normal and trisomic fetuses as well as in dermal fibroblasts of fetuses with trisomy 18. LAMA1 and LAMA3 genes are located on chromosome 18. Dermal cysts were found in the skin of trisomy 18

  3. 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.

    Science.gov (United States)

    Siddens, Lisbeth K; Bunde, Kristi L; Harper, Tod A; McQuistan, Tammie J; Löhr, Christiane V; Bramer, Lisa M; Waters, Katrina M; Tilton, Susan C; Krueger, Sharon K; Williams, David E; Baird, William M

    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 8h post-initiation. A significant reduction in levels of Cyp 1a1, Nqo1 at 8h 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 4h 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 8h 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. PMID:26049101

  4. Preparation of studies on antibody production against food allergens in mice and effect of flavonoids in simultaneous injection into mouse skin.

    Science.gov (United States)

    We had tried to evaluate antibody production against food allergens in mouse models. Some food allergens, which were beta-lactoglobulin, ovalbumin, and peanut allergen Ara h 1, were used as immunoges in this experiment. Under the same conditions these allergens were immunized as emulsion with freund...

  5. Co-expression of sCD40LIg and CTLA4Ig mediated by adenovirus prolonged mouse skin allograft survival

    Institute of Scientific and Technical Information of China (English)

    LI Zhao-lun; TIAN Pu-xun; XUE Wu-jun; WU Jun

    2006-01-01

    Objective: To investigate the role of simultaneous blockade of CD40/CD40L and B7/CD28 pathways in the immune tolerance via co-expression of sCD40LIg and CTLA4Ig mediated by replication-defective adenovirus. Methods: Ad-sCD40LIgIRES2-CTLA4Ig, replication-defective adenovirus co-expressing sCD40LIg and CTLA4Ig, was constructed and identified. The co-expression of sCD40LIg and CTLA4Ig was evaluated with confocal laser scanning microscope and Western blotting. Skin transplantations of C57BL/6 to BALB/c mice were performed. PBS, Ad-Shuttle-CMV and Ad-sCD40LIg-IRES2-CTLA4Ig were administered. Skin graft survival was monitored and the mRNA expression of both genes was evaluated in the skin allografts.Results: Ad-sCD40LIg-IRES2-CTLA4Ig was constructed successfully and identified. The co-expression of sCD40LIg and CTLA4Ig was identified with confocal laser scanning microscopy and Western blotting. Compared to the skin graft mean survival time (MST) of non-treated group ((5.75±0.71) d) or Ad-Shuttle-CMV-treated group ((5.50±0.53) d), the skin graft MST was dramatically prolonged in the Ad-sCD40LIg-IRES2-CTLA4Ig-treated group (( 16.38± 1.19) d, P<0.001). The mRNA expression of both genes was detected. Conclusion: Ad-sCD40LIg-IRES2-CTLA4Ig, a replication-defective adenovirus carrying genes encoding sCD40LIg and CTLA4Ig, was constructed. Simultaneous blockade of CD40/CD40L and B7/CD28 costimulatory pathway mediated by replication-defective adenovirus significantly prolonged skin allograft survival in mice.

  6. 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.

  7. 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. PMID:25478867

  8. 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.

    Science.gov (United States)

    Tiwari, Prakash; Gupta, Krishna P

    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. PMID:24792773

  9. 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.

  10. 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.

  11. 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. PMID:26655363

  12. 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.

  13. Aging Skin

    Science.gov (United States)

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

  14. 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, ...

  15. 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.

  16. 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

  17. 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

  18. 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. PMID:27573915

  19. 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.

  20. 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

    International Nuclear Information System (INIS)

    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

  1. 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.

  2. 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

  3. Trypanosoma cruzi: in vivo evaluation of iron in skin employing X-ray fluorescence (XRF) in mouse strains that differ in their susceptibility to infection.

    Science.gov (United States)

    Estevam, Marcelo; Appoloni, Carlos Roberto; Malvezi, Aparecida Donizette; Tatakihara, Vera Lúcia Hideko; Panis, Carolina; Cecchini, Rubens; Rizzo, Luiz Vicente; Pinge-Filho, Phileno

    2012-04-01

    Trypanosoma cruzi, the causative agent of Chagas' disease (CD), is a substantial public health concern in Latin America. Laboratory mice inoculated with T. cruzi have served as important animal models of acute CD. Host hypoferremic responses occur during T. cruzi infection; therefore, it has been hypothesized that T. cruzi requires iron for optimal growth in host cells and, unlike extracellular pathogens, may benefit from host hypoferremic responses. Recent technological improvements of X-ray fluorescence are useful for diagnostics or monitoring in biomedical applications. The goal of our study was to determine whether the iron availabilities in Swiss and C57BL/6 mice differ during the acute phase of T. cruzi infection and whether the availability correlates with oxidative stress in the susceptible and resistant phenotypes identified in these mice. Our results showed that the decrease in iron levels in the skin of resistant infected mice correlated with the increase in oxidative stress associated with anemia and the reduction in parasite burden. PMID:22136203

  4. Keloid-derived, plasma/fibrin-based skin equivalents generate de novo dermal and epidermal pathology of keloid fibrosis in a mouse model.

    Science.gov (United States)

    Lee, Yun-Shain; Hsu, Tim; Chiu, Wei-Chih; Sarkozy, Heidi; Kulber, David A; Choi, Aaron; Kim, Elliot W; Benya, Paul D; Tuan, Tai-Lan

    2016-03-01

    Keloids are wounding-induced tumor-like human scars. Unclear etiology and lack of animal models to reveal disease mechanisms and invent therapies deepen the grievous health and psychosocial state of vulnerable individuals. Epitomizing the injury-repair environment which triggers and fosters keloid formation and essential dermal/epidermal interactions in disease development, the novel animal model was established by implanting porous polyethylene ring-supported plasma/fibrin-based epidermal-dermal skin constructs on the dorsum of athymic NU/J mice. The implants were stable to 18 weeks, contained abundant human cells, and remodeled to yield scar architecture characteristic of keloid fibrosis compared with normal implants and clinical specimens: (1) macroscopic convex or nodular scar morphology; (2) morphogenesis and accumulation of large collagen bundles from collagen-null initial constructs; (3) epidermal hyperplasia, aberrant epidermal-dermal patency, and features of EMT; (4) increased vasculature, macrophage influx, and aggregation; and (5) temporal-spatial increased collagen-inducing PAI-1 and its interactive partner uPAR expression. Development of such pathology in the NU/J host suggests that T-cell participation is less important at this stage than at keloid initiation. These accessible implants also healed secondary excisional wounds, enabling clinically relevant contemporaneous wounding and treatment strategies, and evaluation. The model provides a robust platform for studying keloid formation and testing knowledge-based therapies. PMID:26683740

  5. Sagging Skin

    Science.gov (United States)

    ... turkey neck,” this occurs as skin loses its elasticity and in cases where individuals have lost a ... technique or procedure is appropriate for my skin type? Did the doctor show me before-and-after ...

  6. Skin Dictionary

    Science.gov (United States)

    ... resources Meet our partners Español Donate Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases Cosmetic treatments Dry / sweaty skin Eczema / dermatitis Hair and scalp ...

  7. Skin Biopsy

    Science.gov (United States)

    ... skin condition cannot be diagnosed by the patient's history and what the physician finds on examination alone. Confirming a clinical diagnosis may also be necessary prior to starting therapy. Skin biopsy types are as follows: Shave biopsies Punch biopsies ...

  8. 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.

  9. Skin Cancer

    Science.gov (United States)

    Skin cancer is the most common form of cancer in the United States. The two most common types ... face, neck, hands, and arms. Another type of skin cancer, melanoma, is more dangerous but less common. Anyone ...

  10. 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.

  11. SKIN CANCER

    OpenAIRE

    Made Putri Hendaria; AAGN Asmarajaya; Sri Maliawan

    2013-01-01

    Skin is an organ which protect the human body from the environment. It was build by milion cells. According to the changes in human lifestyle which tends to unhealthy life, increasing ultraviolet radiation, toxins, and genetics makes the cells who build the skin do the abnormal growth being cancer cells. Classification of skin cancer is according the most common three types, they are Basal Cell Carcinoma, Squamous Cell Carcinoma, and Malignant Melanoma. More than 3,5 milion skin cancer cases ...

  12. 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 ...

  13. 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

  14. Undergraduate Laboratory Module on Skin Diffusion

    Science.gov (United States)

    Norman, James J.; Andrews, Samantha N.; Prausnitz, Mark R.

    2011-01-01

    To introduce students to an application of chemical engineering directly related to human health, we developed an experiment for the unit operations laboratory at Georgia Tech examining diffusion across cadaver skin in the context of transdermal drug delivery. In this laboratory module, students prepare mouse skin samples, set up diffusion cells…

  15. Skin Diseases: Skin Health and Skin Diseases

    Science.gov (United States)

    ... Usually the cause is staphylococcal (staph), but sometimes streptococcus (strep) can cause it, too. It is most ... color or outline, or in any other way. Psoriasis © 2008 Logical Images, Inc. Psoriasis —A skin disease ...

  16. Curious Skin

    OpenAIRE

    Angel, G.

    2010-01-01

    Some of Henry Wellcome’s collection of tattoos on human skin will be on display in our forthcoming Skin exhibition. But how did the Parisian doctor from whom they were acquired come by his macabre collection of tattoos in the first place, and what did they mean to those whose skin they were on? It’s Gemma Angel‘s job to find out…

  17. 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 ...

  18. 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)

  19. Skin Cancer in Skin of Color

    OpenAIRE

    Bradford, Porcia T.

    2009-01-01

    Skin cancers in skin of color often present atypically or with advanced stage in comparison to Caucasian patients. Health care providers must maintain a high index of suspicion when examining skin lesions in skin of color.

  20. Skin abscess

    Science.gov (United States)

    ... infection (often staphylococcus) A minor wound or injury Boils Folliculitis (infection in a hair follicle) A skin ... Elsevier Churchill Livingstone; 2009:chap 90. Read More Boils Endocarditis Folliculitis MRSA Osteomyelitis Update Date 11/12/ ...

  1. Skin graft

    Science.gov (United States)

    ... caused a large amount of skin loss Burns Cosmetic reasons or reconstructive surgeries where there has been ... Smoking increases your chance of problems such as slow healing. Ask your doctor or nurse for help ...

  2. Skin Pigment

    Science.gov (United States)

    ... This Article Medical Dictionary Also of Interest (Quiz) Vitiligo (Video) Hives Additional Content Medical News Overview of ... Version Pigment Disorders Overview of Skin Pigment Albinism Vitiligo Hyperpigmentation Melasma Melanin is the brown pigment that ...

  3. Skin Cancer Screening

    Science.gov (United States)

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

  4. 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.

  5. 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.

  6. Innate lymphoid cells and the skin

    OpenAIRE

    Salimi, Maryam; Ogg, Graham

    2014-01-01

    Innate lymphoid cells are an emerging family of effector cells that contribute to lymphoid organogenesis, metabolism, tissue remodelling and protection against infections. They maintain homeostatic immunity at barrier surfaces such as lung, skin and gut (Nature 464:1367–1371, 2010, Nat Rev Immunol 13: 145–149, 2013). Several human and mouse studies suggest a role for innate lymphoid cells in inflammatory skin conditions including atopic eczema and psoriasis. Here we review the innate lymphoid...

  7. 金雀异黄素对D-半乳糖损伤的乳鼠皮肤成纤维细胞的作用%Study of genistein on mouse skin fibroblasts injured by D-galactose

    Institute of Scientific and Technical Information of China (English)

    顾翠英; 韩志芬; 夏花英; 蒋嘉烨; 曹红平; 金国琴

    2012-01-01

    Objective To observe the effects of genistein (Gen) on the mouse skin fibroblasts (MSFs) injured by D-galactose and investigate the mechanisms. Methods MSFs were cultured in vitro, then Gen was used to affect the model cells injured by D-galactose. The morphostructure of the MSFs were observed with microscope. The vitalities of superoxide dismutase ( SOD) , lactic acid dehydrogenase (LDH) , and the content of malondialdehyde (MDA) were measured by kit methods. Erαand ERβmRNA were detected by RT-PCR method. Results Compared with model group, 0. 5 mg/L Gen could improve the content of MDA, increase the vitalities of SOD and LDH (P < 0.01) markedly. Gen could decrease the expression of Erα mRNA (P<0. 05) and increase Erβ mRNA (P<0. 05) obviously. Conclusions 0. 5 mg/L Gen can improve ER mRNA, enhance the vitality of SOD and antioxidation, increase the content of MDA and the vitality of LDH, change the biological characteristics of MSFs, inhibit MSFs proliferation.%目的 观察金雀异黄素(Gen)对D-半乳糖(D-gal)损伤的小鼠皮肤成纤维细胞(MSFs)模型的作用,并探索其机制.方法 体外培养MSFs,D-gal制作细胞损伤模型,并用Gen进行干预.显微镜下观察各组MSFs生长形态变化;试剂盒法检测MSFs上清液中超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量和乳酸脱氢酶(LDH)活性;RT-PCR法检测MSFs的雌激素受体雌激素受体(ER)α和ERβ mRNA的表达.结果 与模型组相比,浓度为0.5 mg/L Gen能显著提高SOD活性,同时亦提高MDA含量和LDH活性(P<0.01);明显下调ERα mRNA表达(P<0.05),上调ERβmRNA表达(P<0.05).结论 浓度为0.5 mg/L Gen可以通过改善模型细胞ER mRNA的表达,提高SOD活性和抗氧化作用;同时升高MDA含量和LDH活性,改变MSFs的生物学特性,抑制其过度增殖.

  8. 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...

  9. Skin Care and Aging

    Science.gov (United States)

    ... page please turn Javascript on. Skin Care and Aging How Aging Affects Skin Your skin changes with age. It ... if they bother you. See additional resources on aging skin, including information on treatment options, specific conditions, ...

  10. 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 ...

  11. 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 ...

  12. Skin Substitutes

    OpenAIRE

    Zavan, Barbara; Vindigni, Vincenzo; Cortivo, Roberta; Abatangelo, Giovanni

    2010-01-01

    The many studies conducted so far reveal that Tissue Engineering of the skin is only at the beginning of its use in human applications. Burns patients were the first targets for such tissue substitutes, then chronic diseases, such as venous ulcers, have followed. The more experience is gained from the surgeon, the more feedback for the basic scientist to improve the product and to broaden clinical indications. Nowadays, progress in cell culture and biomedical material technologies have added ...

  13. Skin aging:

    OpenAIRE

    Puizina-Ivić, Neira

    2008-01-01

    There are two main processes that induce skin aging: intrinsic and extrinsic. A stochastic process that implies random cell damage as a result of mutations during metabolic processes due to the production of free radicals is also implicated. Extrinsic aging is caused by environmental factors such as sun exposure, air pollution, smoking, alcohol abuse, and poor nutrition. Intrinsicaging reflects the genetic background and depends on time. Various expressions of intrinsic aging include smooth, ...

  14. Mouse adhalin

    DEFF Research Database (Denmark)

    Liu, L; Vachon, P H; Kuang, W;

    1997-01-01

    analyze the biological roles of adhalin, we cloned the mouse adhalin cDNA, raised peptide-specific antibodies to its cytoplasmic domain, and examined its expression and localization in vivo and in vitro. The mouse adhalin sequence was 80% identical to that of human, rabbit, and hamster. Adhalin was...... specifically expressed in striated muscle cells and their immediate precursors, and absent in many other cell types. Adhalin expression in embryonic mouse muscle was coincident with primary myogenesis. Its expression was found to be up-regulated at mRNA and protein levels during myogenic differentiation in...

  15. 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 ...

  16. 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.

  17. 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

  18. Effects of Selenium on DNA Binding Activity of Nuclear Factor-κB Induced by Arsenic in Mouse Skin JB6-CI41 Cells in vitro%硒对砷诱导小鼠皮肤JB6-CI41细胞核因子κB的DNA结合活性体外实验研究

    Institute of Scientific and Technical Information of China (English)

    余日安; 贺凌飞; 鲁文清; 李晓暖; 王艺陪; 陈秉; 戴文涛

    2012-01-01

    目的 研究硒对砷诱导小鼠皮肤JB6-CI41细胞核因子κB(nuclear factor κB,NF-κB)的DNA结合活性和细胞凋亡的作用.方法 调整JB6-CI41细胞密度为1×105/孔,分别设立对照(生理盐水)组,不同浓度的亚砷酸(3.125、6.25、12.5 μmol/L)和亚硒酸钠(2.5 μmol/L)单独染毒组,亚硒酸钠(2.5μmol/L)+不同浓度的亚砷酸(3.125、6.25和12.5μmol/L)联合染毒组,NF-κB特异化学抑制剂二乙基二硫代氨基甲酸盐(diethyldithiocarbamate,DTYC,100 μmol/L,提前染毒2 h)+亚砷酸(6.25 μmol/L)联合染毒组.采用凝胶阻滞电泳法(electrophoretic mobility shift assay,EMSA)检测NF-κB的DNA结合活性,采用流式细胞术检测细胞凋亡情况.结果 2.5 μmol/L亚硒酸钠对小鼠皮肤JB6-CI41细胞NF-κB的DNA结合活性和细胞凋亡无显著影响(P>0.05).6.25和12.5 μmol/L的亚砷酸能够增强小鼠皮肤JB6-CI41细胞NF-κB的DNA结合活性(P<0.01),具有明显剂量-效应关系(r=0.942 6,P<0.01).3.125、6.25和12.5 μmol/L亚砷酸诱导小鼠皮肤JB6-CI41细胞凋亡(P<0.01),呈现显著剂量-反应关系(r=0.991 8,P<0.01).NF-κB的DNA结合活性与细胞凋亡率呈显著正相关(r=0.977 5,P<0.01).2.5 μmol/L亚硒酸钠能抑制6.25和12.5 μmol/L亚砷酸作用下的小鼠皮肤JB6-CI41细胞NF-κB的DNA结合活性(P<0.01),对3.125、6.25和12.5 μmol/L的亚砷酸引起的小鼠皮肤JB6-CI41细胞凋亡率也表现出显著抑制作用(P<0.01).100 μmol/L的DTYC对6.25μmol/L亚砷酸引起的小鼠皮肤JB6-CI41细胞NF-κB的DNA结合活性和细胞凋亡率具有显著抑制作用(P<0.01).结论 在本实验中,一定剂量(6.25~12.5 μmol/L)的砷能够使小鼠皮肤JB6-CI41细胞NF-κB的DNA结合活性显著增高并诱导细胞凋亡,2.5 μmol/L的硒能抑制砷引起的NF-κB的活化和细胞凋亡.%Objective To explore the effects of selenium on arsenic-induced DNA binding activity of nuclear factor κB (NF-κB) and apoptosis in mouse skin JB6-CI

  19. 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.

  20. 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.

  1. Skin Immunity to Candida albicans.

    Science.gov (United States)

    Kashem, Sakeen W; Kaplan, Daniel H

    2016-07-01

    Candida albicans is a dimorphic commensal fungus that colonizes healthy human skin, mucosa, and the reproductive tract. C. albicans is also a predominantly opportunistic fungal pathogen, leading to disease manifestations such as disseminated candidiasis and chronic mucocutaneous candidiasis (CMC). The differing host susceptibilities for the sites of C. albicans infection have revealed tissue compartmentalization with tailoring of immune responses based on the site of infection. Furthermore, extensive studies of host genetics in rare cases of CMC have identified conserved genetic pathways involved in immune recognition and the response to the extracellular pathogen. We focus here on human and mouse skin as a site of C. albicans infection, and we review established and newly discovered insights into the cellular pathways that promote cutaneous antifungal immunity. PMID:27178391

  2. 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

  3. Anyone Can Get Skin Cancer

    Science.gov (United States)

    ... Cancer Skin Cancer Screening Research Anyone Can Get Skin Cancer Order the free Anyone Can Get Skin Cancer ... true that only people with light skin get skin cancer? No. Anyone can get skin cancer. It's more ...

  4. 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.

  5. Learning about Skin Cancer

    Science.gov (United States)

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

  6. Skin care and incontinence

    Science.gov (United States)

    Incontinence - skin care ... or bowels (called incontinence) are at risk of skin problems around the buttocks, hips, genitals, and the ... rectum (perineum). Excess moisture in these areas makes skin problems such as redness, peeling, irritation, and yeast ...

  7. 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.

  8. 荧光原位杂交法观察小鼠皮肤组织切片中型无绿藻感染的研究%Detection of Prototheca zopfii infection in mouse skin tissue sections by using fluorescence in situ hybridization

    Institute of Scientific and Technical Information of China (English)

    康俞莉; 赵颖; 章强强

    2014-01-01

    Objective To evaluate the feasibility to detect Prototheca in a mouse model of Prototheca zopfii cutaneous infection by using fluorescence in situ hybridization (FISH).Methods The model of Prototheca zopfii cutaneous infection was established by abdominal subcutaneous inoculation of Prototheca zopfii suspensions into 20 male BALB/c mice.Seven days after the inoculation,the mice were sacrificed,and tissue specimens were obtained from abdominal skin and subjected to microscopic examination,fungal culture and paraffin embedding.A PZ-probe was artificially synthesized and used to detect Prototheca in paraffin-embedded sections by using FISH.Moreover,both periodic acid-Schiff (PAS) and hematoxylin-eosin (HE) staining were performed to examine the paraffin-embedded sections.Skin specimens obtained from normal mice and Candida albicans-or Cryptococcus neoformans-infected mice served as the negative control.Results Clinical presentations,pathological examination and fungal culture results all confirmed the successful establishment of Prototheca zopfii skin infection model in mice.Prototheca was identified by FISH with the PZ-probe in the paraffin-embedded skin tissue sections from the murine model of Prototheca zopfii cutaneous infection,but not detected in the negative control tissue specimens,which was consistent with the results of PAS and HE staining.Conclusion FISH can be used to detect Prototheca in paraffin-embedded skin sections from the mouse model of Prototheca zopfii cutaneous infection.%目的 探讨荧光原位杂交技术用于诊断小鼠皮肤中型无绿藻感染模型的可行性.方法 制作小鼠皮肤中型无绿藻感染模型,制备皮肤组织石蜡切片,用人工合成的探针PZ-probe进行荧光原位杂交检测,以过碘酸锡夫(PAS)染色、HE染色做阳性对照;取正常及其他真菌感染的皮肤组织石蜡切片做阴性对照,以同样的方法进行荧光原位杂交检测,将各种检测方法的结果进行对比分析.结果

  9. The City Mouse and the Country Mouse

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Once two mice (老鼠) were good friends. One lived in the city, the other lived in the country (乡村). After many years, the city mouse came to see the country mouse. The country mouse took him to his house in a field. He gave him the nicest food that he could find. The city mouse said,

  10. Chemically induced skin carcinogenesis: Updates in experimental models (Review).

    Science.gov (United States)

    Neagu, Monica; Caruntu, Constantin; Constantin, Carolina; Boda, Daniel; Zurac, Sabina; Spandidos, Demetrios A; Tsatsakis, Aristidis M

    2016-05-01

    Skin cancer is one of the most common malignancies affecting humans worldwide, and its incidence is rapidly increasing. The study of skin carcinogenesis is of major interest for both scientific research and clinical practice and the use of in vivo systems may facilitate the investigation of early alterations in the skin and of the mechanisms involved, and may also lead to the development of novel therapeutic strategies for skin cancer. This review outlines several aspects regarding the skin toxicity testing domain in mouse models of chemically induced skin carcinogenesis. There are important strain differences in view of the histological type, development and clinical evolution of the skin tumor, differences reported decades ago and confirmed by our hands‑on experience. Using mouse models in preclinical testing is important due to the fact that, at the molecular level, common mechanisms with human cutaneous tumorigenesis are depicted. These animal models resemble human skin cancer development, in that genetic changes caused by carcinogens and pro‑inflammatory cytokines, and simultaneous inflammation sustained by pro‑inflammatory cytokines and chemokines favor tumor progression. Drugs and environmental conditions can be tested using these animal models. keeping in mind the differences between human and rodent skin physiology. PMID:26986013

  11. Dry Skin (Xerosis)

    Science.gov (United States)

    ... resources Meet our partners Español Donate Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ... Dry skin public SPOT Skin Cancer™ Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases ...

  12. Estrogens and aging skin

    OpenAIRE

    Thornton, M. Julie

    2013-01-01

    Estrogen deficiency following menopause results in atrophic skin changes and acceleration of skin aging. Estrogens significantly modulate skin physiology, targeting keratinocytes, fibroblasts, melanocytes, hair follicles and sebaceous glands, and improve angiogenesis, wound healing and immune responses. Estrogen insufficiency decreases defense against oxidative stress; skin becomes thinner with less collagen, decreased elasticity, increased wrinkling, increased dryness and reduced vascularity...

  13. Skin Cancer Prevention

    Science.gov (United States)

    ... the lower part of the epidermis. They make melanin , the pigment that gives skin its natural color. When skin is exposed to the sun, melanocytes make more pigment, causing the skin to tan, or darken. The dermis contains blood and lymph vessels , hair follicles , and glands . Enlarge Anatomy of the skin, ...

  14. Stiff skin syndrome.

    Science.gov (United States)

    Geng, S; Lei, X; Toyohara, J P; Zhan, P; Wang, J; Tan, S

    2006-07-01

    Stiff skin syndrome is a rare disorder characterized by pronounced skin induration, mild hypertrichosis and limited joint mobility, predominantly on the buttocks and thighs. Many heterogeneous cases have been reported under the name of stiff skin syndrome. We present a case of stiff skin syndrome from China, the diagnosis based on the patient's typical clinical and histopathological features. PMID:16836505

  15. Allergy testing - skin

    Science.gov (United States)

    Patch tests - allergy; Scratch tests - allergy; Skin tests - allergy; RAST test ... There are three common methods of allergy skin testing. The skin prick test involves: Placing a small amount of substances that may be causing your symptoms on the skin, most often ...

  16. Risks of Skin Cancer Screening

    Science.gov (United States)

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

  17. Keratoacanthoma Pathobiology in Mouse Models

    Directory of Open Access Journals (Sweden)

    Katherine N. Gibson-Corley

    2014-05-01

    Full Text Available Recently we described skin tumors driven by skin-specific expression of Zmiz1 and here we define keratoacanthoma pathobiology in this mouse model. Similar to human keratoacanthoma development, we were able to segregate murine keratoacanthomas into three developmental phases: growth, maturation, and regression. These tumors had areas with cellular atypia, high mitotic rate, and minor local invasion in the growth phase, but with development they transitioned to maturation and regression phases with evidence of resolution. The early aggressive appearance could easily be misdiagnosed as a malignant change if the natural pathobiology was not well-defined in the model. To corroborate these findings in the Zmiz1 model, we examined squamous skin tumors from another tumor study in aging mice, and these tumors followed a similar biological progression. Lastly, we were able to evaluate the utility of the model to assess immune cell infiltration (F4/80, B220 Granzyme B, CD3 cells, arginase-1 in the regression phase; however, because inflammation was present at all phases of development, a more comprehensive approach will be needed in future investigations. Our study of keratoacanthomas in selected murine models suggests that these squamous tumors can appear histologically aggressive during early development, but with time will enter a regression phase indicating a benign biology. Importantly, studies of squamous skin tumor models should be cautious in tumor diagnosis as the early growth distinction between malignant versus benign based solely on histopathology may not be easily discerned without longitudinal studies to confirm the tumor pathobiology.

  18. 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)

  19. [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.

  20. 17种生物碱类药物体外经皮渗透行为的实验研究%To Study in Vitro Percutaneous Absorption of 17 Alkaloidal Drugs with Mouse Skin

    Institute of Scientific and Technical Information of China (English)

    许景峰

    2001-01-01

    目的研究生物碱类药物经皮吸收系数与药物油/水分配系数的关系。方法采用Ficks扩散装置测定17种生物碱类药物在小鼠皮的透皮速率,并与含2%促渗剂氮酮比较。结果生物碱类药物的经皮渗透系数(kp)与药物油/水分配系数(logk)的关系式为:logkp=7.35×10-2-3.079×10-2logk-8.11(logk)2;logkp(2%Azo)=8.32×10-2-2.68×10-2logk-5.27(logk)2;结论 17种药物的油/水分配系数平均最佳值为2.83,含2%氮酮后的其平均最佳值为3.17。%Aim To study the relationship between permeability coefficient and oil/water partition coefficient of 17 alkaloidal drugs.Methods The percutaneous absorption speed of 17 alkaloidal drugs were studied in mouse with improved Fick's diffusing device.Results The relationship between permeability coefficient (kp) and oil/water partition coefficient (logk) of 17 alkaloidal drugs or drugs containing 2% Azone can be described as following equations.logkp=7.35×10-2-3.079×10-2logk-8.11(logk)2;logkp(2%Azo)=8.32×10-2-2.68×10-2logk-5.27(logk)2,respectively.Conclusion ko/w and ko/w(2%Azo) was 2.83 and 3.17 respectively.

  1. 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).

  2. Healthy Skin Matters

    Science.gov (United States)

    ... your health, talk to your doctor or a physical therapist to find out what kinds of activities are ... the treatment of diseases of the skin. Follicle (FALL-lick-el). The opening in the skin where ...

  3. Dry Skin Relief

    Science.gov (United States)

    ... resources Meet our partners Español Donate Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases Cosmetic treatments Dry / sweaty skin Eczema / dermatitis Hair and scalp ...

  4. CSD skin test

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003385.htm CSD skin test To use the sharing features on this page, please enable JavaScript. The cat scratch disease (CSD) skin test was once used to help ...

  5. Squamous cell skin cancer

    Science.gov (United States)

    ... earliest form of squamous cell cancer is called Bowen disease (or squamous cell carcinoma in situ). This type ... cancer; Squamous cell carcinoma of the skin Images Bowen's disease on the hand Keratoacanthoma Keratoacanthoma Skin cancer, squamous ...

  6. Skin lesion KOH exam

    Science.gov (United States)

    ... KOH exam is a test to diagnose a fungal infection of the skin . How the Test is Performed ... Performed This test is done to diagnose a fungal infection of the skin. Normal Results No fungus is ...

  7. Stages of Skin Cancer

    Science.gov (United States)

    ... cells than in normal cells. For skin cancer, laser light is shined onto the skin and the drug becomes active and kills the cancer cells. Photodynamic therapy causes little damage to healthy tissue. Biologic therapy ...

  8. Skin Cancer Treatment

    Science.gov (United States)

    ... cells than in normal cells. For skin cancer, laser light is shined onto the skin and the drug becomes active and kills the cancer cells. Photodynamic therapy causes little damage to healthy tissue. Biologic therapy ...

  9. Skin Cancer Trends

    Science.gov (United States)

    ... Search The CDC Cancel Submit Search The CDC Skin Cancer Note: Javascript is disabled or is not supported ... Cervical Colorectal (Colon) Lung Ovarian Prostate Cancer Home Skin Cancer Trends Language: English Español (Spanish) Recommend on Facebook ...

  10. 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.

  11. The effect of microneedles on the skin permeability and antitumor activity of topical 5-fluorouracil

    Directory of Open Access Journals (Sweden)

    Youssef W. Naguib

    2014-02-01

    Full Text Available Topical 5-fluorouracil (5-FU is approved for the treatment of superficial basal cell carcinoma and actinic keratosis. However, 5-FU suffers from poor skin permeation. Microneedles have been successfully applied to improve the skin permeability of small and large molecules, and even nanoparticles, by creating micron-sized pores in the stratum corneum layer of the skin. In this report, the feasibility of using microneedles to increase the skin permeability of 5-FU was tested. Using full thickness mouse skin mounted on Franz diffusion apparatus, it was shown that the flux of 5-FU through the skin was increased by up to 4.5-fold when the skin was pretreated with microneedles (500 μm in length, 50 μm in base diameter. In a mouse model with B16-F10 mouse melanoma cells implanted in the subcutaneous space, the antitumor activity of a commercially available 5-FU topical cream (5% was significantly enhanced when the cream was applied on a skin area that was pretreated with microneedles, as compared to when the cream was simply applied on a skin area, underneath which the tumor cells were implanted, and without pretreatment of the skin with microneedles. Fluorouracil is not approved for melanoma therapy, but the clinical efficacy of topical 5-FU against tumors such as basal cell carcinoma may be improved by integrating microneedle technology into the therapy.

  12. 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

  13. 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

  14. 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.

  15. 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 ...

  16. Anyone Can Get Skin Cancer

    Science.gov (United States)

    No matter if your skin is light, dark, or somewhere in between, everyone is at risk for skin cancer. Learn what skin cancer looks like, how to find it early, and how to lower the chance of skin cancer.

  17. What Is Melanoma Skin Cancer?

    Science.gov (United States)

    ... statistics for melanoma skin cancer What is melanoma skin cancer? Cancer starts when cells in the body begin ... causing the skin to tan or darken. Melanoma skin cancers Melanoma is a cancer that begins in the ...

  18. Multistage skin tumor promotion: involvement of a protein kinase

    Energy Technology Data Exchange (ETDEWEB)

    Mamrack, M.; Slaga, T. J.

    1980-01-01

    Current information suggests that chemical carcinogenesis is a multistep process with one of the best studied models in this regard being the two-stage carcinogenesis system using mouse skin. The effects of several carcinogens and tumor promoters in various sequences of application were studied to examine the nature of the process. The actions of several tumor inhibitors were compared. (ACR)

  19. 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. PMID:27376685

  20. 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.

  1. Dorsoventral patterning of the mouse coat by Tbx15.

    OpenAIRE

    Candille, Sophie I.; Van Raamsdonk, Catherine D.; Changyou Chen; Sanne Kuijper; Yanru Chen-Tsai; Andreas Russ; Frits Meijlink; Barsh, Gregory S.

    2004-01-01

    Many members of the animal kingdom display coat or skin color differences along their dorsoventral axis. To determine the mechanisms that control regional differences in pigmentation, we have studied how a classical mouse mutation, droopy ear (de(H)), affects dorsoventral skin characteristics, especially those under control of the Agouti gene. Mice carrying the Agouti allele black-and-tan (a(t)) normally have a sharp boundary between dorsal black hair and yellow ventral hair; the de(H) mutati...

  2. Skin aging modulates percutaneous drug absorption: the impact of ultraviolet irradiation and ovariectomy

    OpenAIRE

    Hung, Chi-Feng; Chen, Wei-Yu; Aljuffali, Ibrahim A.; Lin, Yin-Ku; Shih, Hui-Chi; Fang, Jia-you

    2015-01-01

    Ultraviolet (UV) exposure and menopause are known as the inducers of damage to the skin structure. The combination of these two factors accelerates the skin aging process. In this study, we aimed to evaluate the influence of UV and ovariectomy (OVX) on the permeation of drugs through the skin. The role of tight junctions (TJs) and adherens junctions (AJs) in the cutaneous absorption of extremely lipophilic permeants and macromolecules was explored. The OVX nude mouse underwent bilateral ovary...

  3. 强脉冲光照射对小鼠皮肤胶原纤维、弹性纤维及透明质酸含量的影响%Effects of intense pulsed light irradiation on the content of collagen fibers, elastic fibers and hyaluronic acid in Kunming mouse skin

    Institute of Scientific and Technical Information of China (English)

    邓列华; 刘赛君; 胡云峰; 赵刚; 林泽; 赵永铿

    2010-01-01

    Objective To investigate the effects of intense pulsed light (IPL) irradiation on the content of collagen fibers, elastic fibers and hyaluronic acid in Kunming mouse skin. Methods The dorsal skin of mice was divided into two areas: the right area was irradiated with IPL, and the left remaining unirradiated served as the control. Skin specimens were taken from the back of mice on day 1, 3, week 1, 2, 4 and 8 after the irradiation and subjected to staining with HE, sirius red and Gomori aldehyde-fuchsin for examinations of histological changes, type Ⅰ and Ⅲ collagen fibers and elastic fibers. The hydroxyproline and hyaluronic acid content in skin tissues of mice was determined with ultraviolet spectrophotometry and radioimmunoassay respectively. Results After irradiation, a significant increase was observed in dermal thickness on week 2 (t =4.623, P< 0.05), 4, and 8 (t = 3.904, P< 0.05), in type Ⅲ collagen fiber (t = 5.129, P< 0.05) on week 1,in type Ⅰ and Ⅲ collagen fibers on week 2, 4 and 8 (both P< 0.05), in elastic fibers from week 2 to 8 (P <0.05), and in hydroxyproline content from week 1 to 8 (all P < 0.05) in the skin of mice compared with unirradiated mice. In detail, dermal thickness increased by 18.71% on week 4, and type Ⅲ collagen fiber by 40.54% in irradiated mice compared with unirradiated mice. Further more, the hyaluronic acid content was elevated from day 1 to 3, but gradually declined from week 1 to 8, and remained statistically higher from day 1 to week 8 (P < 0.05) in irradiated mice compared to unirradiated mice. Conclusion IPL irradiation could induce an increase in the content of collagen fiber, elastic fiber and hyaluronic acid in the dorsal skin of mice.%目的 探讨强脉冲光照射对昆明小鼠皮肤胶原纤维、弹性纤维、透明质酸含量的意义.方法 用强脉冲光照射小鼠右侧背部皮肤,左侧为对照,取各时间点照射组和对照组皮肤进行组织学观察,包括HE染色、Ⅰ

  4. Archaea on human skin

    OpenAIRE

    Alexander J Probst; Auerbach, Anna K.; Christine Moissl-Eichinger

    2013-01-01

    The recent era of exploring the human microbiome has provided valuable information on microbial inhabitants, beneficials and pathogens. Screening efforts based on DNA sequencing identified thousands of bacterial lineages associated with human skin but provided only incomplete and crude information on Archaea. Here, we report for the first time the quantification and visualization of Archaea from human skin. Based on 16 S rRNA gene copies Archaea comprised up to 4.2% of the prokaryotic skin mi...

  5. Skin tribology: Science friction?

    OpenAIRE

    Heide, van der, M.; X. Zeng; 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 frequently one of the interacting surfaces in relative motion. People seem to solve these problems related to skin friction based upon a trial-and-error strategy and based upon on our sense for touch....

  6. 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.

  7. Neuromodulators for Aging Skin

    Science.gov (United States)

    ... Skin Rejuvenation Soft-tissue Fillers Combination: Soft-tissue Fillers and Neuromodulators Neuromodulators – wrinkle-relaxing injections of botulinum toxin commercially known as Botox, Dysport ...

  8. 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 (skin barrier function, pharmaceutical delivery and wound dressings.

  9. 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. PMID:25961580

  10. 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.

  11. Shark skin: function in locomotion.

    Science.gov (United States)

    Wainwright, S A; Vosburgh, F; Hebrank, J H

    1978-11-17

    Hydrostatic pressure under the skin of sharks varies with swimming speed. Stress in the skin varies with the internal pressure, and the skin stress controls skin stiffness. Locomotory muscles attach to the skin which is thus a whole-body exotendon whose mechanical advantage in transmitting muscular contraction is greater than that of the endoskeleton. PMID:17807247

  12. Gaze beats mouse

    DEFF Research Database (Denmark)

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

    2008-01-01

    pointing was faster than mouse pointing, while maintaining a similar error rate. EMG and mouse-button selection had a comparable performance. From analyses of completion time, throughput and error rates, we concluded that the combination of gaze and facial EMG holds potential for outperforming the mouse....

  13. 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 ...

  14. 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...

  15. 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.

  16. 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.

  17. 6 Common Cancers - Skin Cancer

    Science.gov (United States)

    ... Home Current Issue Past Issues 6 Common Cancers - Skin Cancer Past Issues / Spring 2007 Table of Contents For ... Photo: AP Photo/Herald-Mail, Kevin G. Gilbert Skin Cancer Skin cancer is the most common form of ...

  18. Skin and Psyche : Diversionary Symbiosis

    OpenAIRE

    Sharma, YK; Sudarsanan, S.; Bhatnagar, A

    2005-01-01

    A significant proportion of patients with skin diseases have associated psychosocial factors. Not only does psychopathology manifest on the skin in absence of any real skin disease, primary skin disorders can also be exacerbated by emotional stress adversely influencing the homeostasis of immunological and inflammatory processes in deeper layers of the skin. Furthermore, many patients develop emotional problems as a result of having disfiguring skin diseases. In addition, some patients having...

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. Occupational skin cancers

    Energy Technology Data Exchange (ETDEWEB)

    Gawkrodger, D.J. [Royal Hallamshire Hospital, Sheffield (United Kingdom). Dept. of Dermatology

    2004-10-01

    Skin cancer due to occupation is more common than is generally recognized, although it is difficult to obtain an accurate estimate of its prevalence. Over the past two centuries, occupational skin cancers have particularly been due to industrial exposure of men (it seems more so than women) to chemical carcinogens such as polycyclic hydrocarbons (e.g. from coal tar products) or to arsenic. Industrial processes have improved in most Western countries to limit this type of exposure, but those with outdoor occupations are still exposed to solar ultraviolet irradiation without this being widely recognized as an industrial hazard. Ionizing radiation such as X-rays can also cause skin cancer. Occupational skin cancers often resemble skin tumours found in non-occupational subjects, e.g. basal cell carcinoma, squamous cell carcinoma and malignant melanoma, but some pre-malignant lesions can be more specific and point to an occupational origin, e.g. tar keratoses or arsenical keratoses. An uncommon but well-recognized cause of occupational skin cancer is that which results from scar formation following an industrial burn. In the future it will be necessary to focus on preventative measures, e.g. for outdoor workers, the need to cover up in the sun and use sun protective creams and a campaign for earlier recognition of skin cancers, which are usually curable if treated in their early stages.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. An in vitro human skin test for assessing sensitization potential.

    Science.gov (United States)

    Ahmed, S S; Wang, X N; Fielding, M; Kerry, A; Dickinson, I; Munuswamy, R; Kimber, I; Dickinson, A M

    2016-05-01

    Sensitization to chemicals resulting in an allergy is an important health issue. The current gold-standard method for identification and characterization of skin-sensitizing chemicals was the mouse local lymph node assay (LLNA). However, for a number of reasons there has been an increasing imperative to develop alternative approaches to hazard identification that do not require the use of animals. Here we describe a human in-vitro skin explant test for identification of sensitization hazards and the assessment of relative skin sensitizing potency. This method measures histological damage in human skin as a readout of the immune response induced by the test material. Using this approach we have measured responses to 44 chemicals including skin sensitizers, pre/pro-haptens, respiratory sensitizers, non-sensitizing chemicals (including skin-irritants) and previously misclassified compounds. Based on comparisons with the LLNA, the skin explant test gave 95% specificity, 95% sensitivity, 95% concordance with a correlation coefficient of 0.9. The same specificity and sensitivity were achieved for comparison of results with published human sensitization data with a correlation coefficient of 0.91. The test also successfully identified nickel sulphate as a human skin sensitizer, which was misclassified as negative in the LLNA. In addition, sensitizers and non-sensitizers identified as positive or negative by the skin explant test have induced high/low T cell proliferation and IFNγ production, respectively. Collectively, the data suggests the human in-vitro skin explant test could provide the basis for a novel approach for characterization of the sensitizing activity as a first step in the risk assessment process. PMID:26251951

  9. 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

  10. 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 ...

  11. Skin Allergy Quiz

    Science.gov (United States)

    ... Training Grants & Awards Program Directors Practice Resources ASTHMA IQ Consultation and Referral Guidelines Practice Financial Survey Practice ... Your local allergist can do a skin prick test or blood test to find out if you ...

  12. Laser Skin Renewal

    Science.gov (United States)

    ... rashes clinical tools newsletter | contact Share | Skin Renewal, Laser A A A BEFORE: This patient wanted the appearance of his acne scars minimized by laser treatment. Procedure Overview Photorejuvenation, simply put, is the ...

  13. Aging changes in skin

    Science.gov (United States)

    ... areas. Changes in the connective tissue reduce the skin's strength and elasticity. This is known as elastosis. It is more ... chemicals Indoor heating Sunlight can cause: Loss of elasticity ... growths (keratoacanthomas) Pigment changes such as liver spots ...

  14. 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, ...

  15. Skin color - patchy

    Science.gov (United States)

    ... such as from the sun) Exposure to heavy metals Changes in hormone levels Exposure to sun or ultraviolet (UV) light, especially after taking a medicine called psoralens, may increase skin color (pigmentation). Increased ...

  16. Layers of the Skin

    Science.gov (United States)

    ... Review Abstracting, Coding, & Staging ICD-O Site Codes Morphology & Grade Extent of Disease Evaluation Physical Exam Lab ... the majority of the structure of the skin, hair, and nails. The squamous cell layer is the ...

  17. Necrotizing Skin Infections

    Science.gov (United States)

    ... and Treatment Medical Dictionary Also of Interest (Quiz) Vitiligo (Video) Hives Additional Content Medical News Necrotizing Skin ... Professional Version Also of Interest Test your knowledge Vitiligo is a loss of melanocytes (cells that produce ...

  18. Fungal Skin Infections

    Science.gov (United States)

    ... Skin Infections Medical Dictionary Also of Interest (Quiz) Vitiligo (Video) Hives Additional Content Medical News Overview of ... Professional Version Also of Interest Test your knowledge Vitiligo is a loss of melanocytes (cells that produce ...

  19. Human Skin Fungal Diversity

    OpenAIRE

    Findley, Keisha; OH, JULIA; Yang, Joy; Conlan, Sean; Deming, Clayton; Meyer, Jennifer A.; Schoenfeld, Deborah; Nomicos, Effie; Park, Morgan; ,; Kong, Heidi H.; Segre, Julia A

    2013-01-01

    Traditional culture-based methods have incompletely defined the etiology of common recalcitrant human fungal skin diseases including athlete’s foot and toenail infections. Skin protects humans from invasion by pathogenic microorganisms, while providing a home for diverse commensal microbiota 1 . Bacterial genomic sequence data have generated novel hypotheses about species and community structures underlying human disorders 2,3,4 . However, microbial diversity is not limited to bacteria; micro...

  20. 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.

  1. 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.

  2. 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. PMID:24635573

  3. 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.

  4. 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.

  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. 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. PMID:27310436

  7. 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.

  8. 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 ...

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

    OpenAIRE

    Stamatoyannopoulos, John A; Guig?? Serra, Roderic; Djebali, Sarah; Lagarde, Julien; Adams, Leslie B.

    2012-01-01

    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.

  10. 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.

  11. 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...

  12. 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.

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

    Science.gov (United States)

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

    2009-02-01

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

  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. In vivo stepwise multi-photon activation fluorescence imaging of melanin in human skin

    Science.gov (United States)

    Lai, Zhenhua; Gu, Zetong; Abbas, Saleh; Lowe, Jared; Sierra, Heidy; Rajadhyaksha, Milind; DiMarzio, Charles

    2014-03-01

    The stepwise multi-photon activated fluorescence (SMPAF) of melanin is a low cost and reliable method of detecting melanin because the activation and excitation can be a continuous-wave (CW) mode near infrared (NIR) laser. Our previous work has demonstrated the melanin SMPAF images in sepia melanin, mouse hair, and mouse skin. In this study, we show the feasibility of using SMPAF to detect melanin in vivo. in vivo melanin SMPAF images of normal skin and benign nevus are demonstrated. SMPAF images add specificity for melanin detection than MPFM images and CRM images. Melanin SMPAF is a promising technology to enable early detection of melanoma for dermatologists.

  16. 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…

  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. Epidermal skin grafting.

    Science.gov (United States)

    Herskovitz, Ingrid; Hughes, Olivia B; Macquhae, Flor; Rakosi, Adele; Kirsner, Robert

    2016-09-01

    Autologous skin grafts, such as full- and split-thickness, have long been part of the reconstructive ladder as an option to close skin defects. Although they are effective in providing coverage, they require the need for a trained surgeon, use of anaesthesia and operating room and creation of a wound at the donor site. These drawbacks can be overcome with the use of epidermal skin grafts (ESGs), which can be harvested without the use of anaesthesia in an office setting and with minimal to no scarring at the donor site. ESGs consist only of the epidermal layer and have emerged as an appealing alternative to other autologous grafts for the treatment of acute and chronic wounds. In this article, we provide an overview of epidermal grafting and its role in wound management. PMID:27547964

  19. Thyroid and skin

    Directory of Open Access Journals (Sweden)

    Dogra Alka

    2006-01-01

    Full Text Available The association of thyroid disorders with skin manifestations is complex. Both hypothryoidism and hyperthyroidism are known to cause these changes. In order to study this association of skin changes in relation to hypothyroidism, a study was carried out in the outpatients department of Dermatology of Dayanand Medical College and Hospital, Ludhiana, over a period of 3 months from Jan-March 2005. Thirty two patients were enrolled in the study and parameters were noted regarding history, general symptoms, cutaneous signs and associated diseases. We found gain in weight (71.85% and lethargy (65.62% to be the most common complaints. On cutaneous examination, dry, coarse texture of the skin (56%, pigmentary disorders (37.5% and telogen effluvium (40.62% were the most common findings. Other associated disorders were vitiligo, melasma, pemphigus, alopecia areata, xanthelasma palpebrarum, etc.

  20. 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.

  1. Contact Sensitizers Induce Skin Inflammation via ROS Production and Hyaluronic Acid Degradation

    OpenAIRE

    Esser, Philipp R.; Ute Wölfle; Christoph Dürr; Friederike D von Loewenich; Schempp, Christoph M.; Freudenberg, Marina A.; Thilo Jakob; Martin, Stefan F.

    2012-01-01

    BACKGROUND: Allergic contact dermatitis (ACD) represents a severe health problem with increasing worldwide prevalence. It is a T cell-mediated skin disease induced by protein-reactive organic and inorganic chemicals. A key feature of contact allergens is their ability to trigger an innate immune response that leads to skin inflammation. Previous evidence from the mouse contact hypersensitivity (CHS) model suggests a role for endogenous activators of innate immune signaling. Here, we analyzed ...

  2. Contact Sensitizers Induce Skin Inflammation via ROS Production and Hyaluronic Acid Degradation

    OpenAIRE

    Philipp R Esser; Wölfle, Ute; Dürr, Christoph; Friederike D von Loewenich; Schempp, Christoph M.; Freudenberg, Marina A.; Jakob, Thilo; Martin, Stefan F

    2012-01-01

    Background Allergic contact dermatitis (ACD) represents a severe health problem with increasing worldwide prevalence. It is a T cell-mediated skin disease induced by protein-reactive organic and inorganic chemicals. A key feature of contact allergens is their ability to trigger an innate immune response that leads to skin inflammation. Previous evidence from the mouse contact hypersensitivity (CHS) model suggests a role for endogenous activators of innate immune signaling. Here, we analyzed t...

  3. 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.

  4. Limitations of skin protection.

    Science.gov (United States)

    Schliemann, Sibylle

    2007-01-01

    Skin protection products and gloves are essential constituents of personal protective equipment at workplaces, which can be used in a complementary way, each offering particular benefits and disadvantages. In many workplace situations, both measures are being used either in an alternating or in a combined manner, typically in professions with exposures to mild irritants and a high wet-work load, such as hairdressers, healthcare workers or employees in the food-processing industry. Skin protection creams can be used to reduce unnecessarily long glove usage in order to reduce occlusion-related effects on the skin barrier. Whenever rotating machines are used, these products are the only option due to safety regulations. However, some particular requirements can be postulated for skin-protective products claimed especially to be used in combination with gloves. Reduction of glove-induced perspiration, of stratum corneum swelling, and postocclusive barrier impairment are intended attributes of such products, which have been already successfully implemented in some commercially available products. On the other hand it has to be proven that the ingredients do not interfere with the glove material, neither in the way of degrading the material, thus making it permeable for harmful substances, nor by enhancing the potential release of rubber allergens. Examples out of the literature are reviewed showing that skin products can exhibit unpredictable effects on the allergen release of rubber materials, if not thoroughly tested for this purpose beforehand. Some raw materials should be avoided in protection products, though they are of established value when used in afterwork emollients to accelerate barrier recovery. Usage of moisturizers, in contrast to special barrier products, at the workplace together or even under gloves is therefore judged critically, although selected products showed beneficial effects in particular experimental settings. Another future option is the

  5. 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.

  6. 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.

  7. 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

  8. Intelligent skin: Real virtual

    OpenAIRE

    Bühlmann, Vera

    2006-01-01

    What will it feel like to live in a city, where houses court each other in springtime? The 'intelligent-skin' project investigates the potential of media-façades in terms of corporate communication: what does it mean to build houses out of bricks of mediality? What does it imply to say that communication literally takes place? The virtualization of housing through large sized media skins will introduce medial milieus into our urban spheres to come – they might seize to function as add-ons...

  9. 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. PMID:21923733

  10. 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.

  11. 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.

  12. 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.

  13. Promotion of hair follicle development and trichogenesis by Wnt-10b in cultured embryonic skin and in reconstituted skin

    International Nuclear Information System (INIS)

    We previously showed that Wnt-10b promoted the differentiation of primary skin epithelial cells (MPSEC) toward hair shaft and inner root sheath of the hair follicle (IRS) cells in vitro. In the present study, we found that Wnt-10b promotes the development of hair follicles using a culture of mouse embryonic skin tissue and trichogenesis using a reconstitution experiment with nude mice. Hair follicle development was observed in skin taken from mouse embryos on embryonic day 10.5 following a 2-day culture with recombinant Wnt-10b (rWnt-10b), however, not without rWnt-10b. Brown hair growth was observed at the site of reconstituted skin in Balb/c nude mice where dermal fibroblasts and keratinocytes, derived from C3H/HeN new born mice, were transplanted with Wnt-10b-producing COS cells (Wnt-COS). Without the co-transplantation of Wnt-COS, no hair growth was observed. Our results suggest an important role of Wnt-10b in the initiation of hair follicle development and following trichogenesis

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

    Science.gov (United States)

    ... Prenatal Baby Bathing & Skin Care Breastfeeding Crying & Colic Diapers & Clothing Feeding & Nutrition Preemie Sleep Teething & Tooth Care Toddler Preschool Gradeschool Teen Young Adult Healthy Children > Ages & Stages > Baby > Preemie > About Skin- ...

  15. Immunity and skin cancer

    Energy Technology Data Exchange (ETDEWEB)

    Smith, E.B.; Brysk, M.M.

    1981-01-01

    Observations in humans and animal studies support the theory that immunologic surveillance plays an important role in limiting the development of skin malignancies. These immune responses undergo progressive diminution with age. In addition, other factors, such as bereavement, poor nutrition, and acute and chronic exposure to ultraviolet light, can further diminish immune mechanisms.

  16. 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.

  17. Skin Conditions during Pregnancy

    Science.gov (United States)

    ... line that runs from the navel to the pubic hair • Stretch marks •Acne • Spider veins • Varicose veins • Changes ... Nigra: A line running from the navel to pubic hair that darkens during pregnancy. Melasma: A common skin ...

  18. Light and skin disease

    International Nuclear Information System (INIS)

    Because of the depletion of ozone in the stratosphere due to chlorofluorocarbons, the screening effect of this ozone layer on ultraviolet radiation (especially the so-called UV-B component) is reduced. This paper describes the impact of increased UV radiation on the human skin. Because of the 'ozone-hole', a distinct increase in the rate of skin cancer is to be expected which will affect all living beings but most of all man - an indirect consequence of the climate development. What makes the increased intensity of UV-B radiation so harmful is the fact that light-induced skin damage accumulates for the period of the life-time of the individual and cannot be reversed. A further thinning of stratospheric ozone would let through, in addition, the more short-waved ('harder') UV-C radiation. The latter, though clinically not significant currently, would then account for a further increase in the rate of malignant skin disease world-wide. (orig.)

  19. Slicing, skinning, and grafting

    OpenAIRE

    Dumas, David; Kent IV, Richard P.

    2007-01-01

    We prove that a Bers slice is never algebraic, meaning that its Zariski closure in the character variety has strictly larger dimension. A corollary is that skinning maps are never constant. The proof uses grafting and the theory of complex projective structures.

  20. Smoking and skin disease

    DEFF Research Database (Denmark)

    Thomsen, S F; Sørensen, L T

    2010-01-01

    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...... wounds. Most likely, alteration of inflammatory cell function and extracellular matrix turnover caused by smoking-induced oxidative stress are involved in the pathophysiologic mechanisms....

  1. Cytokines and the Skin Barrier

    Directory of Open Access Journals (Sweden)

    Jens Malte Baron

    2013-03-01

    Full Text Available The skin is the largest organ of the human body and builds a barrier to protect us from the harmful environment and also from unregulated loss of water. Keratinocytes form the skin barrier by undergoing a highly complex differentiation process that involves changing their morphology and structural integrity, a process referred to as cornification. Alterations in the epidermal cornification process affect the formation of the skin barrier. Typically, this results in a disturbed barrier, which allows the entry of substances into the skin that are immunologically reactive. This contributes to and promotes inflammatory processes in the skin but also affects other organs. In many common skin diseases, including atopic dermatitis and psoriasis, a defect in the formation of the skin barrier is observed. In these diseases the cytokine composition within the skin is different compared to normal human skin. This is the result of resident skin cells that produce cytokines, but also because additional immune cells are recruited. Many of the cytokines found in defective skin are able to influence various processes of differentiation and cornification. Here we summarize the current knowledge on cytokines and their functions in healthy skin and their contributions to inflammatory skin diseases.

  2. Skin color independent assessment of aging using skin autofluorescence

    NARCIS (Netherlands)

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

    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

  3. 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.

  4. Tips for Relieving Dry Skin

    Science.gov (United States)

    ... resources Meet our partners Español Donate Diseases and treatments Acne and rosacea Bumps and growths Color problems Contagious skin diseases Cosmetic treatments Dry / sweaty skin Eczema / dermatitis Hair and scalp ...

  5. Skin lesion removal-aftercare

    Science.gov (United States)

    ... aftercare; Nevi - removal aftercare; Scissor excision aftercare; Skin tag removal aftercare; Mole removal aftercare; Skin cancer removal ... to the principles of the Health on the Net Foundation (www.hon.ch). The information provided herein ...

  6. 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.

  7. Radiation Therapy for Skin Cancer

    Science.gov (United States)

    ... skin cells called melanocytes that produce skin color ( melanin ). Radiation therapy is used mostly for melanomas that ... in addition to surgery, chemotherapy or biologic therapy. Hair Epidermis Dermis Subcutaneous Hair Follicle Vein Artery © ASTRO ...

  8. 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 ...

  9. 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.

  10. Drugs Approved for Skin Cancer

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Skin Cancer This page lists cancer drugs approved by the Food and Drug Administration (FDA) for skin cancer, including drugs for basal cell carcinoma and melanoma. ...

  11. Tissue Engineered Human Skin Equivalents

    OpenAIRE

    Zheng Zhang; Michniak-Kohn, Bozena B.

    2012-01-01

    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 commerc...

  12. 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...

  13. Skin Cancers of the Feet

    Science.gov (United States)

    ... skin of the lower legs and feet. Skin cancers affecting the feet may have a very different appearance from those arising on the rest of the body. For this reason, a podiatrist's knowledge and clinical training is of ... and malignant skin tumors. Learn the ABCDs of melanoma. If you notice ...

  14. 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…

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

    International Nuclear Information System (INIS)

    The skin cancer enhancing effect of chromium (in male mice) and nickel in UVR-irradiated female Skh1 mice was investigated. The dietary vitamin E and selenomethionine were tested for prevention of chromium-enhanced skin carcinogenesis. The mice were exposed to UVR (1.0 kJ/m2 3x weekly) for 26 weeks either alone, or combined with 2.5 or 5.0 ppm potassium chromate, or with 20, 100 or 500 ppm nickel chloride in drinking water. Vitamin E or selenomethionine was added to the lab chow for 29 weeks beginning 3 weeks before the start of UVR exposure. Both chromium and nickel significantly increased the UVR-induced skin cancer yield in mice. In male Skh1 mice, UVR alone induced 1.9 ± 0.4 cancers/mouse, and 2.5 or 5.0 ppm potassium chromate added to drinking water increased the yields to 5.9 ± 0.8 and 8.6 ± 0.9 cancers/mouse, respectively. In female Skh1 mice, UVR alone induced 1.7 ± 0.4 cancers/mouse, and the addition of 20, 100 or 500 ppm nickel chloride increased the yields to 2.8 ± 0.9, 5.6 ± 0.7 and 4.2 ± 1.0 cancers/mouse, respectively. Neither vitamin E nor selenomethionine reduced the cancer yield enhancement by chromium. These results confirm that chromium and nickel, while not good skin carcinogens per se, are enhancers of UVR-induced skin cancers in Skh1 mice. Data also suggest that the enhancement of UVR-induced skin cancers by chromate may not be oxidatively mediated since the antioxidant vitamin E as well as selenomethionine, found to prevent arsenite-enhanced skin carcinogenesis, failed to suppress enhancement by chromate

  16. 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...

  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. 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.

  19. 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.

  20. Skin barrier in rosacea.

    Science.gov (United States)

    Addor, Flavia Alvim Sant'Anna

    2016-01-01

    Recent studies about the cutaneous barrier demonstrated consistent evidence that the stratum corneum is a metabolically active structure and also has adaptive functions, may play a regulatory role in the inflammatory response with activation of keratinocytes, angiogenesis and fibroplasia, whose intensity depends primarily on the intensity the stimulus. There are few studies investigating the abnormalities of the skin barrier in rosacea, but the existing data already show that there are changes resulting from inflammation, which can generate a vicious circle caused a prolongation of flare-ups and worsening of symptoms. This article aims to gather the most relevant literature data about the characteristics and effects of the state of the skin barrier in rosacea. PMID:26982780

  1. 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.

  2. [Recent development in animal testing to predict the skin and respiratory sensitizing potential of chemicals].

    Science.gov (United States)

    Aoyama, Kohji

    2010-01-01

    The identification of chemicals with skin and/or respiratory sensitizing potential is important for the prevention of allergic diseases in both living and work environments. Although a number of animal models for respiratory allergic diseases have been reported, none of these models meets the goals of broad assessments of chemical sensitizing potential. We are attempting to develop a test for predicting the respiratory sensitization of chemicals. In the evaluation of skin sensitization of chemicals, the mostly used predictive tests are the guinea pig maximization test, Buehler test, and mouse local lymph node assay (LLNA). However, only LLNA has been validated formally and independently. Recent studies have revealed that EC3 estimated by LLNA correlates well with human skin sensitizing potency and the threshold for the induction of skin sensitization in the human repeat patch test. Thus, LLNA can predict the potency of skin sensitizing potential of a chemical and its risk in humans. PMID:20134104

  3. Skin metastases of lung cancer:

    OpenAIRE

    Kecelj, Peter; Košnik, Mitja; Požek, Igor; Triller Vadnal, Katja; Triller, Nadja

    2008-01-01

    Skin metastases of lung cancer are rare. In over a 3-year period we found only14 cases of skin metastases among 1,614 patients with lung cancer admittedto the University Clinic of Respiratory and Allergic Diseases in Golnik. The metastases are usually manifested on the skin of the chest. Skin metastases are symptoms of progressive disease, and usually a sign of a poor prognosis. The median survival time of lung cancer patients with skin metastases was 85 days from the time of detection of the...

  4. 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

  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. Skin-sparing mastectomy.

    Science.gov (United States)

    Simmons, Rache M; Adamovich, Tara L

    2003-08-01

    The cosmetic appearance of the reconstructed breast is largely dependent upon the quantity of breast skin which remains after mastectomy. Leaving behind as much skin as is possible significantly improves the natural appearance of the reconstruction and reduces procedures required on the contralateral breast to achieve symmetry. SSM with immediate reconstruction offers superior aesthetic results to NSSM, with similar LR rates. As most recurrences will occur in chest wall skin, the ability to detect local recurrence is not impaired. The incidence of local wound complications with SSM is comparable to NSSM. It has been demonstrated that sentinel lymph node biopsy and axillary dissection can be performed adequately in SSM. There is no contraindication to postoperative adjuvant chemotherapy and radiation therapy. There are some groups of patients for whom SSM is not indicated, such as patients with inflammatory carcinoma. SSM should be considered for selected patients with breast cancer in conjunction with all types of immediate reconstruction. In conclusion, numerous studies support the use of SSM on selected patients as an oncologically acceptable procedure with superior cosmetic results when compared with traditional NSSM. PMID:12875600

  7. 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...

  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. Effects of Orally Administered Pyrroloquinoline Quinone Disodium Salt on Dry Skin Conditions in Mice and Healthy Female Subjects.

    Science.gov (United States)

    Nakano, Masahiko; Kamimura, Ayako; Watanabe, Fumiko; Kamiya, Toshikazu; Watanabe, Daisuke; Yamamoto, Etsushi; Fukagawa, Mitsuhiko; Hasumi, Keiji; Suzuki, Eriko

    2015-01-01

    Pyrroloquinoline quinone (PQQ) is a coenzyme involved in the redox-cycling system. The supplemental use of PQQ has been examined based on its properties as an antioxidant and redox modulator. Although an animal study on deficiency of PQQ suggested that PQQ contributes to skin conditions, its efficacy in humans has not been reported. The present study aimed to investigate the effects of orally administered PQQ on skin moisture, viscoelasticity, and transepidermal water loss (TEWL) both in dry skin mouse models and in healthy female subjects with a subjective symptom of dry skin. In our dry skin mouse model study, oral intake of PQQ (0.0089%, w/w, in the diet for 6 wk) significantly decreased the number of mast cells in the dermis and the number of CD3⁺ T-cells in the epidermis. In our human study, oral intake of PQQ (20 mg/d for 8 wk) significantly inhibited the increase in TEWL on the forearm. Finally, subject questionnaires showed positive impressions for the improvement of skin conditions. These results suggest that oral intake of PQQ improves skin conditions both in female subjects with dry skin and in mice with a compromised skin barrier function. PMID:26226961

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. [Merkel cell skin carcinoma].

    Science.gov (United States)

    Krejcí, K; Zadrazil, J; Tichý, T; Horák, P; Ciferská, H; Hodulová, M; Zezulová, M; Zlevorová, M

    2010-01-01

    Merkel cell carcinoma is a rare tumour of the skin. It affects predominantly elderly Caucasian males on sun-exposed areas of the skin. Distinctively more frequent and at significantly lower age, its incidence is higher in immunocompromised patients. In these patients we often observe the highly aggressive course of Merkel cell carcinoma and a fatal outcome. The incidence of Merkel cell carcinoma has been rising in recent years and is more dramatic than the increased incidence of cutaneous melanoma. More than one-third of Merkel cell carcinoma patients will die from this cancer, making it twice as lethal as melanoma. The malignant transformation of Merkel cells is currently thought to be related to an infection with Merkel cell polyomavirus. In the early stage the discreet clinical picture may be contrary to extensive microscopic invasion and this seemingly benign appearance can delay diagnosis or increase the risk of insufficient tumour excision. The diagnosis is definitely confirmed by histological evaluation and immunohistochemical tests. A typical feature is the tendency of Merkel cell carcinoma to frequent local recurrence and early metastasizing into regional lymph nodes with subsequent tumour generalization. The mainstay of therapy is radical excision of the tumour and adjuvant radiotherapy targeted at the site of primary incidence and local draining lymph nodes. The efficacy of different chemotherapy protocols in Merkel cell carcinoma is limited and the median survival rate is measured in months. In the future, prophylaxis with vaccination against Merkel cell polyomavirus will hopefully be possible in high-risk patients, as well as therapeutic usage of antisense oligonucleotides or microRNAs, eventually complete Merkel cell carcinoma elimination by affecting the tumour suppressor gene Atonal homolog 1 expression. The staging of the tumour at time of diagnosis is the most important prognostic factor. In this respect, the importance of preventative skin

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. Manipulation of Mouse Embryonic Stem Cells for Knockout Mouse Production

    OpenAIRE

    Limaye, Advait; Hall, Bradford; Kulkarni, Ashok B.

    2009-01-01

    The establishment of mouse embryonic stem (ES) cell liness has allowed for the generation of the knockout mouse. ES cells that are genetically altered in culture can then be manipulated to derive a whole mouse containing the desired mutation. To successfully generate a knockout mouse, however, the ES cells must be carefully cultivated in a pluripotent state throughout the gene targeting experiment. This unit describes detailed step-by-step protocols, reagents, equipment, and strategies needed...

  20. Monitoring collagen remodeling on opto-thermal response of photoaged skin irradiated by Er:YAG laser with optical coherence tomography

    Science.gov (United States)

    Zhang, Xiaoman; Wu, Shulian; Li, Hui

    2010-11-01

    The Optical Coherence Tomography technology was used to perform noninvasive cross-sectional imaging of internal structures in photoaged mouse skin irradiated by Er:YAG laser. The mice were irradiated chronically with a steady dose of ultraviolet irradiation. Various laser light doses were irradiated on the back skins of the photoaged mouse. An OCT was used to observe the process of the collagen remodeling in dermis. The relationship between optical characteristic parameter such as attenuation coefficient and light dose was discovered. The total attenuation coefficient increased when the light dose increased. Our findings showed that Er:YAG laser could be used for the symptoms of the photoaged skin with some degree of thermal damage in the dermis, and the OCT could image the progress of collagen remodeling in photoaged mouse dermis. The OCT may be a useful tool for the determination of optimal parameters for laser skin treatment.

  1. 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.

  2. 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. PMID:26337000

  3. Skin aging modulates percutaneous drug absorption: the impact of ultraviolet irradiation and ovariectomy.

    Science.gov (United States)

    Hung, Chi-Feng; Chen, Wei-Yu; Aljuffali, Ibrahim A; Lin, Yin-Ku; Shih, Hui-Chi; Fang, Jia-You

    2015-01-01

    Ultraviolet (UV) exposure and menopause are known as the inducers of damage to the skin structure. The combination of these two factors accelerates the skin aging process. In this study, we aimed to evaluate the influence of UV and ovariectomy (OVX) on the permeation of drugs through the skin. The role of tight junctions (TJs) and adherens junctions (AJs) in the cutaneous absorption of extremely lipophilic permeants and macromolecules was explored. The OVX nude mouse underwent bilateral ovary removal. Both UVA and UVB were employed to irradiate the skin. The physiological and biochemical changes of the skin structure were examined with focus on transepidermal water loss (TEWL), skin color, immunohistochemistry, and mRNA levels of proteins. UVB and OVX increased TEWL, resulting in stratum corneum (SC) integrity disruption and dehydration. A hyperproliferative epidermis was produced by UVB. UVA caused a pale skin color tone due to keratinocyte apoptosis in the epidermis. E-cadherin and β-catenin showed a significant loss by both UVA and UVB. OVX downregulated the expression of filaggrin and involucrin. A further reduction was observed when UV and OVX were combined. The in vitro cutaneous absorption demonstrated that UV increased the skin permeation of tretinoin by about twofold. However, skin accumulation and flux of estradiol were not modified by photoaging. OVX basically revealed a negligible effect on altering the permeation of small permeants. OVX increased tretinoin uptake by the appendages from 1.36 to 3.52 μg/cm(2). A synergistic effect on tretinoin follicular uptake enhancement was observed for combined UV and OVX. However, the intervention of OVX to photoaged skin resulted in less macromolecule (dextran, molecular weight = 4 kDa) accumulation in the skin reservoir because of retarded partitioning into dry skin. The in vivo percutaneous absorption of lipophilic dye examined by confocal microscopy had indicated that the SC was still important to

  4. 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...

  5. 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.......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....

  6. Neutron Skins and Neutron Stars

    OpenAIRE

    Piekarewicz, J

    2013-01-01

    The neutron-skin thickness of heavy nuclei provides a fundamental link to the equation of state of neutron-rich matter, and hence to the properties of neutron stars. The Lead Radius Experiment ("PREX") at Jefferson Laboratory has recently provided the first model-independence evidence on the existence of a neutron-rich skin in 208Pb. In this contribution we examine how the increased accuracy in the determination of neutron skins expected from the commissioning of intense polarized electron be...

  7. Skin Infections Due to Corynebacterium

    OpenAIRE

    Meltem Türkmen; Derya Aytimur

    2010-01-01

    Corynebacteria are Gram-positive, non-sporulated, non-capsulated, aerobic diphtheroid bacteria accounting for nearly 50%of the natural skin biocene. This bacterial family is responsible for various skin diseases such as cutaneous diphteria, cromhydrosis, bromhydrosis but the most common of them are pitted keratolysis, trichobacteriosis and erythrasma. A warm and moist environment and poor hygiene are the predisposition factors for these three diseases. Although this skin diseases are seen mor...

  8. 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.

  9. [Radiotherapy of skin cancers].

    Science.gov (United States)

    Hennequin, C; Rio, E; Mahé, M-A

    2016-09-01

    The indications of radiotherapy for skin cancers are not clearly defined because of the lack of randomised trials or prospective studies. For basal cell carcinomas, radiotherapy frequently offers a good local control, but a randomized trial showed that surgery is more efficient and less toxic. Indications of radiotherapy are contra-indications of surgery for patients older than 60, non-sclerodermiform histology and occurring in non-sensitive areas. Adjuvant radiotherapy could be proposed to squamous cell carcinomas, in case of poor prognostic factors. Dose of 60 to 70Gy are usually required, and must be modulated to the size of the lesions. Adjuvant radiotherapy seems beneficial for desmoplastic melanomas but not for the other histological types. Prophylactic nodal irradiation (45 to 50Gy), for locally advanced tumours (massive nodal involvement), decreases the locoregional failure rate but do not increase survival. Adjuvant radiotherapy (50 to 56Gy) for Merckel cell carcinomas increases also the local control rate, as demonstrated by meta-analysis and a large epidemiological study. Nodal areas must be included, if there is no surgical exploration (sentinel lymph node dissection). Kaposi sarcomas are radiosensitive and could be treated with relatively low doses (24 to 30Gy). Also, cutaneous lymphomas are good indications for radiotherapy: B lymphomas are electively treated with limited fields. The role of total skin electron therapy for T-lymphomas is still discussed; but palliative radiotherapy is very efficient in case of cutaneous nodules. PMID:27522189

  10. 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.

  11. SKIN KINETICS AND DERMAL CLEARANCE

    Directory of Open Access Journals (Sweden)

    Prakash Shashi

    2012-08-01

    Full Text Available Availability of several therapeutic and cosmetic formulations for topical application has made the research on skin kinetics as a topic of current interest. Topical formulations are typically meant for local effect although there is always a chance that the low molecular weight chemicals are easily transported across the skin layer and make it available in the systemic circulation. Thus there is a major concern about the transport of chemical moieties following the topical application of cosmetics and therapeutic formulations and the real time measurement of the molecules in the skin layer has become obligatory. It is well known that the properties of both drug and the excipients have identical role in determining the skin permeability of chemical moieties. In the last decade several investigations have been carried out in this filed using several in vitro and in vivo models. This review provides a brief account on the basics of skin kinetics, parameters assessed, various techniques and methods adapted in skin kinetic studies. Moreover, we have also discussed about the micro-environment inside the skin layer and the possible mechanism of drug depot formation, skin metabolism and clearance of molecules from the skin layers.

  12. Skin Infections Due to Corynebacterium

    Directory of Open Access Journals (Sweden)

    Meltem Türkmen

    2010-03-01

    Full Text Available Corynebacteria are Gram-positive, non-sporulated, non-capsulated, aerobic diphtheroid bacteria accounting for nearly 50%of the natural skin biocene. This bacterial family is responsible for various skin diseases such as cutaneous diphteria, cromhydrosis, bromhydrosis but the most common of them are pitted keratolysis, trichobacteriosis and erythrasma. A warm and moist environment and poor hygiene are the predisposition factors for these three diseases. Although this skin diseases are seen more frequently, they usually mistaken for a mycotic infection by general practitioners, with subsequent antimycotic treatment. Here skin diseases compromised with Corynebacterium are presented with their demographic features and discussed on the basis of a literature review.

  13. 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.

  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. 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.

  16. 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.

  17. Skin temperature during sunbathing--relevance for skin cancer

    DEFF Research Database (Denmark)

    Petersen, Bibi; Philipsen, Peter Alshede; Wulf, Hans Christian

    2014-01-01

    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...

  18. 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/.

  19. 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.

  20. 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

  1. Mouse-X

    OpenAIRE

    Tagg, Justin

    2014-01-01

    Mouse-X is a short Science Fiction film completed in 2014. It explores identity and reality through a powerful short story about a man trapped in a building with a thousand clones of himself, begging the question, 'Who are you, if you're not the only you?'

  2. Pivotal Role for α1-Antichymotrypsin in Skin Repair*

    OpenAIRE

    Hoffmann, Daniel C.; Textoris, Christine; Oehme, Felix; Klaassen, Tobias; Goppelt, Andreas; Römer, Axel; Fugmann, Burkhard; Davidson, Jeffrey M.; Werner, Sabine; Krieg, Thomas; Eming, Sabine A.

    2011-01-01

    α1-Antichymotrypsin (α1-ACT) is a specific inhibitor of leukocyte-derived chymotrypsin-like proteases with largely unknown functions in tissue repair. By examining human and murine skin wounds, we showed that following mechanical injury the physiological repair response is associated with an acute phase response of α1-ACT and the mouse homologue Spi-2, respectively. In both species, attenuated α1-ACT/Spi-2 activity and gene expression at the local wound site was associated with severe wound h...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    , 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......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...... 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...

  4. 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.

  5. 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.

  6. The Role of Manganese Superoxide Dismutase in Skin Cancer

    Directory of Open Access Journals (Sweden)

    Delira Robbins

    2011-01-01

    Full Text Available Recent studies have shown that antioxidant enzyme expression and activity are drastically reduced in most human skin diseases, leading to propagation of oxidative stress and continuous disease progression. However, antioxidants, an endogenous defense system against reactive oxygen species (ROS, can be induced by exogenous sources, resulting in protective effects against associated oxidative injury. Many studies have shown that the induction of antioxidants is an effective strategy to combat various disease states. In one approach, a SOD mimetic was applied topically to mouse skin in the two-stage skin carcinogenesis model. This method effectively reduced oxidative injury and proliferation without interfering with apoptosis. In another approach, Protandim, a combination of 5 well-studied medicinal plants, was given via dietary administration and significantly decreased tumor incidence and multiplicity by 33% and 57%, respectively. These studies suggest that alterations in antioxidant response may be a novel approach to chemoprevention. This paper focuses on how regulation of antioxidant expression and activity can be modulated in skin disease and the potential clinical implications of antioxidant-based therapies.

  7. Pygmies, Giants, and Skins

    Science.gov (United States)

    Piekarewicz, J.

    2013-03-01

    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.

  8. 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.

  9. 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...... to perform the simulations. To fill in the gap of lacking experimental data a range of measurements was carried out in an outdoor, double-skin façade full-scale test facility ‘The Cube'. As a result, three complete sets of experimental data were composed. These are available for external air curtain......, transparent insulation and preheating operation modes of DSF cavity. The data sets include measurements of naturally induced air flow, temperature gradients, velocity profiles, climate data, etc. Two data sets were used for further empirical validation of building simulation software for DSF modelling within...

  10. Urostomy - stoma and skin care

    Science.gov (United States)

    ... your skin and kidneys. About your stoma Your stoma is made from the part of your small intestine called the ileum. Your ureter is attached to a small piece of your ileum and pulled through the skin of your abdomen. A stoma is very delicate. A healthy stoma is pinkish- ...

  11. Aging Differences in Ethnic Skin.

    Science.gov (United States)

    Vashi, Neelam A; de Castro Maymone, Mayra Buainain; Kundu, Roopal V

    2016-01-01

    Aging is an inevitable and complex process that can be described clinically as features of wrinkles, sunspots, uneven skin color, and sagging skin. These cutaneous effects are influenced by both intrinsic and extrinsic factors and often are varied based on ethnic origin given underlying structural and functional differences. The authors sought to provide updated information on facets of aging and how it relates to ethnic variation given innate differences in skin structure and function. Publications describing structural and functional principles of ethnic and aging skin were primarily found through a PubMed literature search and supplemented with a review of textbook chapters. The most common signs of skin aging despite skin type are dark spots, loss of elasticity, loss of volume, and rhytides. Skin of color has many characteristics that make its aging process unique. Those of Asian, Hispanic, and African American descent have distinct facial structures. Differences in the concentration of epidermal melanin makes darkly pigmented persons more vulnerable to dyspigmentation, while a thicker and more compact dermis makes facial lines less noticeable. Ethnic skin comprises a large portion of the world population. Therefore, it is important to understand the unique structural and functional differences among ethnicities to adequately treat the signs of aging. PMID:26962390

  12. Dry skin - self-care

    Science.gov (United States)

    ... scrubbing your skin. Shave right after bathing, when hair is soft. Wear soft, comfortable clothing next to your skin. Avoid rough fabrics like wool. Wash clothes with detergents that are free of dyes or fragrances. Drink plenty of water. Ease itchy ...

  13. Air Pollution and the skin

    Directory of Open Access Journals (Sweden)

    Eleni eDrakaki

    2014-05-01

    Full Text Available The increase of air pollution over the years has major effects on the human skin. The skin is exposed to ultraviolet radiation (UVR and environmental air pollutants such as polycyclic aromatic hydrocarbons (PAHs, volatile organic compounds (VOCs, oxides, particulate matter (PM, ozone (O3 and cigarette smoke. Although human skin acts as a biological shield against pro-oxidative chemical and physical air pollutants, the prolonged or repetitive exposure to high levels of these pollutants may have profound negative effects on the skin. Exposure of the skin to air pollutants has been associated with skin aging and inflammatory or allergic skin conditions such as atopic dermatitis, eczema, psoriasis or acne, while skin cancer is among the most serious effects. On the other hand, some air pollutants (ie, ozone, nitrogen dioxide, and sulfur dioxide and scattering particulates (clouds and soot in the troposphere reduce the effects of shorter wavelength UVR and significant reductions in UV irradiance have been observed in polluted urban areas.

  14. 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.

  15. Tyrosinase Depletion Prevents the Maturation of Melanosomes in the Mouse Hair Follicle.

    Directory of Open Access Journals (Sweden)

    Elyse K Paterson

    Full Text Available The mechanisms that lead to variation in human skin and hair color are not fully understood. To better understand the molecular control of skin and hair color variation, we modulated the expression of Tyrosinase (Tyr, which controls the rate-limiting step of melanogenesis, by expressing a single-copy, tetracycline-inducible shRNA against Tyr in mice. Moderate depletion of TYR was sufficient to alter the appearance of the mouse coat in black, agouti, and yellow coat color backgrounds, even though TYR depletion did not significantly inhibit accumulation of melanin within the mouse hair. Ultra-structural studies revealed that the reduction of Tyr inhibited the accumulation of terminal melanosomes, and inhibited the expression of genes that regulate melanogenesis. These results indicate that color in skin and hair is determined not only by the total amount of melanin within the hair, but also by the relative accumulation of mature melanosomes.

  16. Tyrosinase Depletion Prevents the Maturation of Melanosomes in the Mouse Hair Follicle.

    Science.gov (United States)

    Paterson, Elyse K; Fielder, Thomas J; MacGregor, Grant R; Ito, Shosuke; Wakamatsu, Kazumasa; Gillen, Daniel L; Eby, Victoria; Boissy, Raymond E; Ganesan, Anand K

    2015-01-01

    The mechanisms that lead to variation in human skin and hair color are not fully understood. To better understand the molecular control of skin and hair color variation, we modulated the expression of Tyrosinase (Tyr), which controls the rate-limiting step of melanogenesis, by expressing a single-copy, tetracycline-inducible shRNA against Tyr in mice. Moderate depletion of TYR was sufficient to alter the appearance of the mouse coat in black, agouti, and yellow coat color backgrounds, even though TYR depletion did not significantly inhibit accumulation of melanin within the mouse hair. Ultra-structural studies revealed that the reduction of Tyr inhibited the accumulation of terminal melanosomes, and inhibited the expression of genes that regulate melanogenesis. These results indicate that color in skin and hair is determined not only by the total amount of melanin within the hair, but also by the relative accumulation of mature melanosomes. PMID:26619124

  17. Topically applied mesoridazine exhibits the strongest cutaneous analgesia and minimized skin disruption among tricyclic antidepressants: The skin absorption assessment.

    Science.gov (United States)

    Liu, Kuo-Sheng; Chen, Yu-Wen; Aljuffali, Ibrahim A; Chang, Chia-Wen; Wang, Jhi-Joung; Fang, Jia-You

    2016-08-01

    Tricyclic antidepressants (TCAs) are found to have an analgesic action for relieving cutaneous pain associated with neuropathies. The aim of this study was to assess cutaneous absorption and analgesia of topically applied TCAs. Percutaneous delivery was investigated using nude mouse and pig skin models at both infinite and saturated doses. We evaluated the cutaneous analgesia in nude mice using the pinprick scores. Among five antidepressants tested in the in vitro experiment, mesoridazine, promazine and doxepin showed a superior total absorption percentage. The drug with the lowest total absorption percentage was found to be fluphenazine (dose or at saturated solubility. The follicular pathway was important for mesoridazine and promazine delivery. Mesoridazine showed stronger skin analgesia than the other TCAs although the in vivo skin absorption of mesoridazine (0.34nmol/mg) was less than that of promazine (0.80nmol/mg) and doxepin (0.74nmol/mg). Mesoridazine had a prolonged duration of pain relief (165min) compared to promazine (83min) and doxepin (17min). The skin irritation test demonstrated an evident barrier function deterioration and cutaneous erythema by promazine and doxepin treatment, whereas mesoridazine caused no obvious adverse effect by topical application for up to 7days. PMID:27260201

  18. In Vivo Two-Photon Microscopy of Single Nerve Endings in Skin

    Science.gov (United States)

    Yuryev, Mikhail; Molotkov, Dmitry

    2014-01-01

    Nerve endings in skin are involved in physiological processes such as sensing1 as well as in pathological processes such as neuropathic pain2. Their close-to-surface positioning facilitates microscopic imaging of skin nerve endings in living intact animal. Using multiphoton microscopy, it is possible to obtain fine images overcoming the problem of strong light scattering of the skin tissue. Reporter transgenic mice that express EYFP under the control of Thy-1 promoter in neurons (including periphery sensory neurons) are well suited for the longitudinal studies of individual nerve endings over extended periods of time up to several months or even life-long. Furthermore, using the same femtosecond laser as for the imaging, it is possible to produce highly selective lesions of nerve fibers for the studies of the nerve fiber restructuring. Here, we present a simple and reliable protocol for longitudinal multiphoton in vivo imaging and laser-based microsurgery on mouse skin nerve endings. PMID:25178088

  19. 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(+), but not...

  20. Skin decontamination of glyphosate from human skin in vitro.

    Science.gov (United States)

    Zhai, H; Chan, H P; Hui, X; Maibach, H I

    2008-06-01

    This study compared three model decontaminant solutions (tap water, isotonic saline, and hypertonic saline) for their ability to remove a model herbicide (glyphosate) from an in vitro human skin model. Human cadaver skin was dosed (approximately 375microg) of [14C]-glyphosate on 3cm2 per skin. After each exposure time (1, 3, and 30min post-dosing, respectively), the surface skin was washed three times (4ml per time) with each solution. After washing, the skin was stripped twice with tape discs. Lastly, the wash solutions, strippings, receptor fluid, and remainder of skin were liquid scintillation analyzer counted to determine the amount of glyphosate. There were no statistical differences among these groups at any time points. The total mass balance recovery at three time exposure points was between 94.8% and 102.4%. The wash off rates (glyphosate in wash solutions) at three different exposure times is 79-101.2%. Thus the three tested decontaminants possess similar effectiveness in removing glyphosate from skin. This in vitro model is not only economic and rapid, but also provides quantitative data that may aid screening for optimal decontaminants. PMID:18407393

  1. 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.

  2. Usefulness of rat skin as a substitute for human skin in the in vitro skin permeation study.

    Science.gov (United States)

    Takeuchi, Hiroyuki; Mano, Yoko; Terasaka, Shuichi; Sakurai, Takanobu; Furuya, Atsushi; Urano, Hidetoshi; Sugibayashi, Kenji

    2011-01-01

    Sprague-Dawley (SD) rats are broadly used in preclinical studies for drug development, so a lot of information for the rats can be obtained especially from pharmacokinetic, pharmacological and toxicological studies. The purpose of this study was to clarify whether SD rat skin can be used to predict human skin permeability. In vitro permeation studies of the three model drugs, nicorandil, isosorbide dinitrate, and flurbiprofen, through human skin and SD rat skin were performed using Franz-type diffusion cells. The permeation rates of the three model drugs through human skin and SD rat skin were determined, and their variations were evaluated. The inter-individual variations in SD rat skin permeability of the three model drugs were much lower than that in human skin permeability, although the permeation rates of the three model drugs through the SD rat skin were about twice those through human skin. In addition, no difference in the skin permeability coefficients of the three model drugs was obtained between fresh SD rat skin and frozen SD rat skin. The markedly smaller variation in the permeability through SD rat skin compared with that through human skin indicated that in vitro permeation studies using SD rat skin would be especially useful for evaluating differences in the skin permeability of the three model drugs as well as for predicting human skin permeability.

  3. 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.

  4. Sun’s effect on skin

    Science.gov (United States)

    The skin uses sunlight to help manufacture vitamin D, which is important for normal bone formation. But sometimes its ultraviolet light can be ... the pigment melanin. Melanin protects skin from the sun's ultraviolet rays, which can burn the skin, and ...

  5. Itchy, Scaly Skin? Living with Psoriasis

    Science.gov (United States)

    ... exit disclaimer . Subscribe Itchy, Scaly Skin? Living With Psoriasis The thick, red, scaly skin of psoriasis can ... Diet Itchy, Scaly Skin? Wise Choices Links Treating Psoriasis Doctors often use a trial-and-error approach ...

  6. Color Constancy For Improving Skin Detection

    OpenAIRE

    A. Nadian-Ghomsheh

    2014-01-01

    Skin detection is a preliminary step in many human related recognition systems. Most skin detection systems suffer from high false detection rate, resulting from low variance between the skin and non-skin color distributions. This paper proposes the use of simple color correction algorithms with low computation complexity to obtain a corrected version of the skin color distribution, which could lead to more accurate skin detection. White patch retinex, Grey world assumption and several improv...

  7. Ultraviolet Light and Skin Cancer in Athletes

    OpenAIRE

    Harrison, Shannon C.; Bergfeld, Wilma F.

    2009-01-01

    The incidence of melanoma and nonmelanoma skin cancers is increasing worldwide. Ultraviolet light exposure is the most important risk factor for cutaneous melanoma and nonmelanoma skin cancers. Nonmelanoma skin cancer includes basal cell carcinoma and squamous cell carcinoma. Constitutive skin color and genetic factors, as well as immunological factors, play a role in the development of skin cancer. Ultraviolet light also causes sunburn and photoaging damage to the skin.

  8. 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.

  9. 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.

  10. 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/.

  11. 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.

  12. Lyme borreliosis and skin.

    Science.gov (United States)

    Vasudevan, Biju; Chatterjee, Manas

    2013-05-01

    Lyme disease is a multisystem illness which is caused by the strains of spirochete Borrelia burgdorferi sensu lato and transmitted by the tick, Ixodes. Though very commonly reported from the temperate regions of the world, the incidence has increased worldwide due to increasing travel and changing habitats of the vector. Few cases have been reported from the Indian subcontinent too. Skin manifestations are the earliest to occur, and diagnosing these lesions followed by appropriate treatment, can prevent complications of the disease, which are mainly neurological. The three main dermatological manifestations are erythema chronicum migrans, borrelial lymphocytoma and acrodermatitis chronica atrophicans. Many other dermatological conditions including morphea, lichen sclerosus and lately B cell lymphoma, have been attributed to the disease. Immunofluorescence and polymerase reaction tests have been developed to overcome the problems for diagnosis. Culture methods are also used for diagnosis. Treatment with Doxycycline is the mainstay of management, though prevention is of utmost importance. Vaccines against the condition are still not very successful. Hence, the importance of recognising the cutaneous manifestations early, to prevent systemic complications which can occur if left untreated, can be understood. This review highlights the cutaneous manifestations of Lyme borreliosis and its management. PMID:23723463

  13. Lyme borreliosis and skin

    Directory of Open Access Journals (Sweden)

    Biju Vasudevan

    2013-01-01

    Full Text Available Lyme disease is a multisystem illness which is caused by the strains of spirochete Borrelia burgdorferi sensu lato and transmitted by the tick, Ixodes. Though very commonly reported from the temperate regions of the world, the incidence has increased worldwide due to increasing travel and changing habitats of the vector. Few cases have been reported from the Indian subcontinent too. Skin manifestations are the earliest to occur, and diagnosing these lesions followed by appropriate treatment, can prevent complications of the disease, which are mainly neurological. The three main dermatological manifestations are erythema chronicum migrans, borrelial lymphocytoma and acrodermatitis chronica atrophicans. Many other dermatological conditions including morphea, lichen sclerosus and lately B cell lymphoma, have been attributed to the disease. Immunofluorescence and polymerase reaction tests have been developed to overcome the problems for diagnosis. Culture methods are also used for diagnosis. Treatment with Doxycycline is the mainstay of management, though prevention is of utmost importance. Vaccines against the condition are still not very successful. Hence, the importance of recognising the cutaneous manifestations early, to prevent systemic complications which can occur if left untreated, can be understood. This review highlights the cutaneous manifestations of Lyme borreliosis and its management.

  14. 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.

  15. Mustard vesicating agent-induced toxicity in the skin tissue and silibinin as a potential countermeasure.

    Science.gov (United States)

    Tewari-Singh, Neera; Agarwal, Rajesh

    2016-06-01

    Exposure to the vesicating agents sulfur mustard (SM) and nitrogen mustard (NM) causes severe skin injury with delayed blistering. Depending upon the dose and time of their exposure, edema and erythema develop into blisters, ulceration, necrosis, desquamation, and pigmentation changes, which persist weeks and even years after exposure. Research advances have generated data that have started to explain the probable mechanism of action of vesicant-induced skin toxicity; however, despite these advances, effective and targeted therapies are still deficient. This review highlights studies on two SM analogs, 2-chloroethyl ethyl sulfide (CEES) and NM, and CEES- and NM-induced skin injury mouse models that have substantially added to the knowledge on the complex pathways involved in mustard vesicating agent-induced skin injury. Furthermore, employing these mouse models, studies under the National Institutes of Health Countermeasures Against Chemical Threats program have identified the flavanone silibinin as a novel therapeutic intervention with the potential to be developed as an effective countermeasure against skin injury following exposure to mustard vesicating agents. PMID:27326543

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Transplantation of human skin microbiota in models of atopic dermatitis

    Science.gov (United States)

    Myles, Ian A.; Williams, Kelli W; Reckhow, Jensen D; Jammeh, Momodou L; Pincus, Nathan B; Sastalla, Inka; Saleem, Danial; Stone, Kelly D; Datta, Sandip K

    2016-01-01

    Atopic dermatitis (AD) is characterized by reduced barrier function, reduced innate immune activation, and susceptibility to Staphylococcus aureus. Host susceptibility factors are suggested by monogenic disorders associated with AD-like phenotypes and can be medically modulated. S. aureus contributes to AD pathogenesis and can be mitigated by antibiotics and bleach baths. Recent work has revealed that the skin microbiome differs significantly between healthy controls and patients with AD, including decreased Gram-negative bacteria in AD. However, little is known about the potential therapeutic benefit of microbiome modulation. To evaluate whether parameters of AD pathogenesis are altered after exposure to different culturable Gram-negative bacteria (CGN) collected from human skin, CGN were collected from healthy controls and patients with AD. Then, effects on cellular and culture-based models of immune, epithelial, and bacterial function were evaluated. Representative strains were evaluated in the MC903 mouse model of AD. We found that CGN taken from healthy volunteers but not from patients with AD were associated with enhanced barrier function, innate immunity activation, and control of S. aureus. Treatment with CGN from healthy controls improved outcomes in a mouse model of AD. These findings suggest that a live-biotherapeutic approach may hold promise for treatment of patients with AD.

  2. Topical Curcumin-Based Cream Is Equivalent to Dietary Curcumin in a Skin Cancer Model

    Directory of Open Access Journals (Sweden)

    Kunal Sonavane

    2012-01-01

    Full Text Available Skin squamous cell carcinoma (SCC, the most common cancer in the USA, is a growing problem with the use of tanning booths causing sun-damaged skin. Antiproliferative effects of curcumin were demonstrated in an aggressive skin cancer cell line SRB12-p9 (P<0.05 compared to control. Topical formulation was as effective as oral curcumin at suppressing tumor growth in a mouse skin cancer model. Curcumin at 15 mg administered by oral, topical, or combined formulation significantly reduced tumor growth compared to control (P=0.004. Inhibition of pAKT, pS6, p-4EBP1, pSTAT3, and pERK1/2 was noted in SRB12-p9 cells post-curcumin treatment compared to control (P<0.05. Inhibition of pSTAT3 and pERK1/2 was also noted in curcumin-treated groups in vivo. IHC analysis revealed human tumor specimens that expressed significantly more activated pERK (P=0.006 and pS6 (P<0.0001 than normal skin samples. This is the first study to compare topical curcumin to oral curcumin. Our data supports the use of curcumin as a chemopreventive for skin SCC where condemned skin is a significant problem. Prevention strategies offer the best hope of future health care costs in a disease that is increasing in incidence due to increased sun exposure.

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

    OpenAIRE

    Desposito, D.; Chollet, C.; Taveau, C.; Descamps, V.; Alhenc-Gelas, F.; Roussel, R.; Bouby, Nadine; Waeckel, L.

    2015-01-01

    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...

  4. Role of Mga in Group A Streptococcal Infection at the Skin Epithelium

    OpenAIRE

    Luo, Feng; Lizano, Sergio; Banik, Sukalyani; Zhang, Hong; Debra E Bessen

    2008-01-01

    Group A streptococci (GAS) primarily cause infection at epithelial tissue sites of its human host. The role of the transcriptional regulator Mga in a humanized mouse model for superficial skin infection was investigated. Inactivation of mga in a skin strain (Alab49) led to loss of virulence. The Δmga mutant displayed >100-fold decrease in emm (pam) transcript levels, and loss of bacterial-bound plasmin activity. A slight decrease in speB transcription, accompanied by a partial decrease in cys...

  5. 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.

  6. 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. PMID:26597116

  7. 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.

  8. Skin Rashes and Other Changes

    Science.gov (United States)

    ... painful red bumps? Yes This could be a BOIL. A cluster of boils is called a CARBUNCLE. These occur due to infection under the skin. Gently compress the boil with a warm cloth. Use antibiotic ointments if ...

  9. Pygmy Resonances and Neutron Skins

    CERN Document Server

    Piekarewicz, J

    2010-01-01

    Motivated by a recent experiment, the distribution of electric dipole strength in the neutron-rich 68Ni isotope was computed using a relativistic random phase approximation with a set of effective interactions that - although well calibrated - predict significantly different values for the neutron-skin thickness in 208Pb. The emergence of low-energy "Pygmy" strength that exhausts about 5-8% of the energy weighted sum rule (EWSR) is clearly identified. In addition to the EWSR, special emphasis is placed on the dipole polarizability. In particular, our results suggest a strong correlation between the dipole polarizability of 68Ni and the neutron-skin thickness of 208Pb. Yet we find a correlation just as strong and an even larger sensitivity between the neutron-skin thickness of 208Pb and the fraction of the dipole polarizability exhausted by the Pygmy resonance. These findings suggest that the dipole polarizability may be used as a proxy for the neutron skin.

  10. 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.

  11. 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.

  12. Taking Care of Your Skin

    Science.gov (United States)

    ... using the product whenever redness or irritation happens. Screening Your Skin From Damage There is one product ... of your parents about whether to use an antibiotic (say: an-tie-bye-AH-tik) cream or ...

  13. Candida infection of the skin

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000880.htm Candida infection of the skin To use the sharing features ... of the warm, moist conditions inside the diaper. Candida infection is particularly common in people with diabetes and ...

  14. 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.

  15. Multimodal photoacoustic ophthalmoscopy in mouse

    OpenAIRE

    Song, Wei; Wei, Qing; Feng, Liang; Sarthy, Vijay; Jiao, Shuliang; LIU, XIAORONG; Zhang, Hao F.

    2012-01-01

    Photoacoustic ophthalmoscopy (PAOM) is a novel imaging technology that measures optical absorption in the retina. The capability of PAOM can be further enhanced if it could image mouse eyes, because mouse models are widely used for various retinal diseases. The challenges in achieving high-quality imaging of mouse retina, however, come from the much smaller eyeball size. Here, we report an optimized imaging system, which integrates PAOM, spectral-domain optical coherence tomography (SD-OCT), ...

  16. Mouse models of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Yunguang Tong; Wancai Yang; H. Phillip Koeffler

    2011-01-01

    Colorectal cancer is one of the most common malignancies in the world. Many mouse models have been developed to evaluate features of colorectal cancer in humans. These can be grouped into genetically-engineered, chemically-induced, and inoculated models. However, none recapitulates all of the characteristics of human colorectal cancer. It is critical to use a specific mouse model to address a particular research question. Here, we review commonly used mouse models for human colorectal cancer.

  17. Mosquito repellents in frog skin

    OpenAIRE

    Williams, C. R.; Smith, B.P.C; Best, S.M.; Tyler, M.J.

    2006-01-01

    The search for novel insect repellents has been driven by health concerns over established synthetic compounds such as diethyl-m-toluamide (DEET). Given the diversity of compounds known from frog skin and records of mosquito bite and ectoparasite infestation, the presence of mosquito repellents in frogs seemed plausible. We investigated frog skin secretions to confirm the existence of mosquito repellent properties. Litoria caerulea secretions were assessed for mosquito repellency by topical a...

  18. [Environmentally induced (extrinsic) skin aging].

    Science.gov (United States)

    Krutmann, J; Schikowski, T; Hüls, A; Vierkötter, A; Grether-Beck, S

    2016-02-01

    Chronic exposure to ultraviolet light, particularly as a component of natural sunlight, is a major cause of environmentally induced aging of the skin. In addition, other environmental factors for premature skin aging include longer wavelength radiation in the visible light region and in particular in the shortwave infrared radiation region. Furthermore, particulate and gaseous components of air pollution significantly contribute to the aging process. PMID:26769311

  19. Clinical utility of skin karyotype

    OpenAIRE

    Luiza E. Dorfman; Agnes F. R. P. Silva; Giorgio A. Paskulin; Rafael F. M. Rosa; Paulo R. G. Zen

    2015-01-01

    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 ...

  20. SKIN KINETICS AND DERMAL CLEARANCE

    OpenAIRE

    Prakash Shashi; Nair Anroop; Saini Vipin; Sahu Neelam

    2012-01-01

    Availability of several therapeutic and cosmetic formulations for topical application has made the research on skin kinetics as a topic of current interest. Topical formulations are typically meant for local effect although there is always a chance that the low molecular weight chemicals are easily transported across the skin layer and make it available in the systemic circulation. Thus there is a major concern about the transport of chemical moieties following the topical application of cosm...

  1. Neutron skin in Osmium isotopes

    International Nuclear Information System (INIS)

    Here we have made an attempt to calculate neutron skin thickness in rare earth even-even osmium isotopes. The selected isotopes ranges from 2-p to 2-n drip line. Neutron skin is an important feature of neutron rich nuclei. The ground state proton and neutron rms radii have been calculated using HFB approximation. A comparison of calculated radii have been done by using two different Skyrme parameterizations and two different basis

  2. Skin signs in anorexia nervosa

    OpenAIRE

    Strumia, Renata

    2009-01-01

    Anorexia nervosa (AN) is a significant cause of morbidity and mortality among adolescent females and young women. AN is associated with severe medical and psychological consequences, including death, osteoporosis, growth delay, and developmental delay. Skin signs are almost always detectable in severe AN and awareness of them may help in the early diagnosis of hidden AN. Skin signs are the expression of the medical consequences of starvation, vomiting, abuse of drugs, such as laxatives and di...

  3. Influence of Nigella sativa fixed oil on some blood parameters and histopathology of skin in staphylococcal-infected BALB/c mice.

    Science.gov (United States)

    Abu-Al-Basal, Mariam A

    2011-12-01

    Nigella sativa has been used for a long time in Jordanian folk medicine to treat skin diseases like microbial infections and inflammation. Therefore, the present study was conducted to assess the healing efficacy of petroleum ether extract of Nigella sativa seeds (fixed oil) on staphylococcal-infected skin. Male BALB/c mice were infected with 100 microL of Staphylococcus aureus (ATCC 6538) suspension at a dose of 10(8) colony forming unit/mouse into shaved mild dorsal skin. Application of treatments for each group (100 microL sterile saline, 100 microL chloramphenicol (10 microg/mouse) and Nigella sativa fixed oil at a dose of 50, 100 or 150 microL/mouse) was performed at the site of infection twice a day for two consecutive days after 3 h of infection. At day 3 and 5 after infection, total White Blood Cells (WBCs) count; differential and absolute differential WBC counts and the number of viable bacteria present in the skin area were measured. At day 5 after infection, the animals were sacrificed and the histology of skin was examined. Results indicated that fixed oil of Nigella sativa seeds enhance healing of staphylococcal-infected skin by reducing total and absolute differential WBC counts, local infection and inflammation, bacterial expansion and tissue impairment. These effects provide scientific basis for the use of Nigella sativa in traditional medicine to treat skin infections and inflammations. PMID:22590837

  4. 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.

  5. 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.

  6. [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.

  7. UV Radiation and the Skin

    Directory of Open Access Journals (Sweden)

    Timothy Scott

    2013-06-01

    Full Text Available UV radiation (UV is classified as a “complete carcinogen” because it is both a mutagen and a non-specific damaging agent and has properties of both a tumor initiator and a tumor promoter. In environmental abundance, UV is the most important modifiable risk factor for skin cancer and many other environmentally-influenced skin disorders. However, UV also benefits human health by mediating natural synthesis of vitamin D and endorphins in the skin, therefore UV has complex and mixed effects on human health. Nonetheless, excessive exposure to UV carries profound health risks, including atrophy, pigmentary changes, wrinkling and malignancy. UV is epidemiologically and molecularly linked to the three most common types of skin cancer, basal cell carcinoma, squamous cell carcinoma and malignant melanoma, which together affect more than a million Americans annually. Genetic factors also influence risk of UV-mediated skin disease. Polymorphisms of the melanocortin 1 receptor (MC1R gene, in particular, correlate with fairness of skin, UV sensitivity, and enhanced cancer risk. We are interested in developing UV-protective approaches based on a detailed understanding of molecular events that occur after UV exposure, focusing particularly on epidermal melanization and the role of the MC1R in genome maintenance.

  8. UV-induced skin damage

    International Nuclear Information System (INIS)

    Solar radiation induces acute and chronic reactions in human and animal skin. Chronic repeated exposures are the primary cause of benign and malignant skin tumors, including malignant melanoma. Among types of solar radiation, ultraviolet B (290-320 nm) radiation is highly mutagenic and carcinogenic in animal experiments compared to ultraviolet A (320-400 nm) radiation. Epidemiological studies suggest that solar UV radiation is responsible for skin tumor development via gene mutations and immunosuppression, and possibly for photoaging. In this review, recent understanding of DNA damage caused by direct UV radiation and by indirect stress via reactive oxygen species (ROS) and DNA repair mechanisms, particularly nucleotide excision repair of human cells, are discussed. In addition, mutations induced by solar UV radiation in p53, ras and patched genes of non-melanoma skin cancer cells, and the role of ROS as both a promoter in UV-carcinogenesis and an inducer of UV-apoptosis, are described based primarily on the findings reported during the last decade. Furthermore, the effect of UV on immunological reaction in the skin is discussed. Finally, possible prevention of UV-induced skin cancer by feeding or topical use of antioxidants, such as polyphenols, vitamin C, and vitamin E, is discussed

  9. 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. PMID:27021875

  10. Impaired skin regeneration and remodeling after cutaneous injury and chemically induced hyperplasia in taps-transgenic mice.

    Science.gov (United States)

    Hildenbrand, Maike; Rhiemeier, Verena; Hartenstein, Bettina; Lahrmann, Bernd; Grabe, Niels; Angel, Peter; Hess, Jochen

    2010-07-01

    Recently, we identified an AP-1-dependent target gene in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated mouse back skin, which encodes a retroviral-like aspartic proteinase (Taps/Asprv1). Taps expression was detected almost exclusively in stratified epithelia of mouse embryos and adult tissues, and enhanced protein levels were present in several non-neoplastic human skin disorders, implicating a crucial role for differentiation and homeostasis of multilayered epithelia. Here, we generated a mouse model in which Taps transgene expression is under the control of the human ubiquitin C promoter (UBC-Taps). Although no obvious phenotype was observed in normal skin development and homeostasis, these mice showed a significant delay in cutaneous wound closure compared with control animals. Shortly after re-epithelialization, we found an increase in keratinocytes in the stratum granulosum, which express Filaggrin, a late differentiation marker. A hypergranulosum-like phenotype with increased numbers of Filaggrin-positive keratinocytes was also observed in UBC-Taps mice after administration of TPA. In summary, these data show that aberrant Taps expression causes impaired skin regeneration and skin remodeling after cutaneous injury and chemically induced hyperplasia. PMID:20237492

  11. Robust Lentiviral Gene Delivery But Limited Transduction Capacity of Commonly Used Adeno-Associated Viral Serotypes in Xenotransplanted Human Skin.

    Science.gov (United States)

    Jakobsen, Maria; Askou, Anne Louise; Stenderup, Karin; Rosada, Cecilia; Dagnæs-Hansen, Frederik; Jensen, Thomas G; Corydon, Thomas J; Mikkelsen, Jacob Giehm; Aagaard, Lars

    2015-08-01

    Skin is an easily accessible organ, and therapeutic gene transfer to skin remains an attractive alternative for the treatment of skin diseases. Although we have previously documented potent lentiviral gene delivery to human skin, vectors based on adeno-associated virus (AAV) rank among the most promising gene delivery tools for in vivo purposes. Thus, 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 skin graft, and firefly luciferase expression was observed primarily in neighboring tissue outside of the graft. In contrast, gene delivery by intradermally injected lentiviral vectors was efficient and led to extensive and persistent firefly luciferase expression within the human skin graft only. The study demonstrates the limited capacity of single-stranded AAV vectors of six commonly used serotypes for gene delivery to human skin in vivo. PMID:26204415

  12. Effect of Rosmarinus officinalis in modulating 7,12-dimethylbenz(a)anthracene induced skin tumorigenesis in mice.

    Science.gov (United States)

    Sancheti, Garima; Goyal, P K

    2006-11-01

    The chemopreventive potential of rosemary (Rosmarinus officinalis) on 7,12-dimethlybenz(a)anthracene (DMBA) initiated and croton oil promoted mouse skin tumorigenesis was assessed. The modulatory effects of R. officinalis was monitored on the basis of the average latency period, tumor incidence, tumor burden, tumor yield, tumor weight and diameter as well as lipid peroxidation and glutathione level. The results indicate that R. officinalis leaves extract could prolong the latency period of tumor occurrence, decrease the tumor incidence, tumor burden and tumor yield. The average weight and diameter of tumors recorded were comparatively lower in the rosemary extract treated mouse groups. The level of lipid peroxidation was significantly reduced in blood serum and liver. Furthermore, depleted levels of glutathione were restored in RE-administered animal groups. Thus, at a dose rate of 500 mg/kg body wt/mouse, the oral administration of rosemary extract was found to be significantly protective against two-stage skin tumorigenesis. PMID:16927448

  13. 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.

  14. 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.

  15. Quiz: Test Your Skin Cancer IQ

    Science.gov (United States)

    ... please turn Javascript on. Feature: Skin Cancer Quiz: Test Your Skin Cancer IQ Past Issues / Summer 2013 Table of Contents 1. ... to Results / Skin and Sun – Safety First / Quiz: Test Your Skin Cancer IQ Summer 2013 Issue: Volume 8 Number 2 Page ...

  16. 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.

  17. Endogenous N-acyl taurines regulate skin wound healing.

    Science.gov (United States)

    Sasso, Oscar; Pontis, Silvia; Armirotti, Andrea; Cardinali, Giorgia; Kovacs, Daniela; Migliore, Marco; Summa, Maria; Moreno-Sanz, Guillermo; Picardo, Mauro; Piomelli, Daniele

    2016-07-26

    The intracellular serine amidase, fatty acid amide hydrolase (FAAH), degrades a heterogeneous family of lipid-derived bioactive molecules that include amides of long-chain fatty acids with taurine [N-acyl-taurines (NATs)]. The physiological functions of the NATs are unknown. Here we show that genetic or pharmacological disruption of FAAH activity accelerates skin wound healing in mice and stimulates motogenesis of human keratinocytes and differentiation of human fibroblasts in primary cultures. Using untargeted and targeted lipidomics strategies, we identify two long-chain saturated NATs-N-tetracosanoyl-taurine [NAT(24:0)] and N-eicosanoyl-taurine [NAT(20:0)]-as primary substrates for FAAH in mouse skin, and show that the levels of these substances sharply decrease at the margins of a freshly inflicted wound to increase again as healing begins. Additionally, we demonstrate that local administration of synthetic NATs accelerates wound closure in mice and stimulates repair-associated responses in primary cultures of human keratinocytes and fibroblasts, through a mechanism that involves tyrosine phosphorylation of the epidermal growth factor receptor and an increase in intracellular calcium levels, under the permissive control of transient receptor potential vanilloid-1 receptors. The results point to FAAH-regulated NAT signaling as an unprecedented lipid-based mechanism of wound-healing control in mammalian skin, which might be targeted for chronic wound therapy. PMID:27412859

  18. Sustained delivery of erythropoietin in mice by genetically modified skin fibroblasts.

    OpenAIRE

    Naffakh, N.; Henri, A; Villeval, J L; Rouyer-Fessard, P; Moullier, P; Blumenfeld, N; Danos, O; Vainchenker, W; Heard, J M; Beuzard, Y.

    1995-01-01

    We have examined whether the secretion of erythropoietin (Epo) from genetically modified cells could represent an alternative to repeated injections of the recombinant hormone for treating chronic anemias responsive to Epo. Primary mouse skin fibroblasts were transduced with a retroviral vector in which the murine Epo cDNA is expressed under the control of the murine phosphoglycerate kinase promoter. "Neo-organs" containing the genetically modified fibroblasts embedded into collagen lattices ...

  19. Bee venom acupuncture alleviates trimellitic anhydride-induced atopic dermatitis-like skin lesions in mice

    OpenAIRE

    Sur, Bongjun; Lee, Bombi; Yeom, Mijung; Hong, Ju-Hee; Kwon, Sunoh; Kim, Seung-Tae; Lee, Hyang Sook; Park, Hi-Joon; Lee, Hyejung; Hahm, Dae-Hyun

    2016-01-01

    Background Bee venom acupuncture (BVA), a novel type of acupuncture therapy in which purified bee venom is injected into the specific acupuncture point on the diseased part of the body, is used primarily for relieving pain and other musculoskeletal symptoms. In the present study, therapeutic potential of BVA to improve atopic dermatitis, a representative allergic dysfunction, was evaluated in the mouse model of trimellitic anhydride (TMA)-induced skin impairment. Methods Mice were treated wit...

  20. 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...