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Sample records for mouse skin topically

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

    PubMed Central

    Tong, Tao; Kim, Nahyun; Park, Taesun

    2015-01-01

    We observed that oleuropein, the main constituent of the leaves and unprocessed olive drupes of Olea europaea, protected mice from high-fat diet-induced adiposity by up-regulation of genes involved in Wnt10b-mediated signaling in adipose tissue. The activation of Wnt/β-catenin pathway is also well established to positively regulate the anagen phase of hair growth cycle in mice skin. Methodology and Principal Findings 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. Conclusions and Significance 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. PMID:26060936

  2. Stimulatory effect of topical application of caffeine on UVB-induced apoptosis in mouse skin.

    PubMed

    Lu, Yao-Ping; Lou, You-Rong; Li, Xiang-Hong; Xie, Jian-Guo; Lin, Yong; Shih, Weichung Joe; Conney, Allan H

    2002-01-01

    In an earlier study, we showed that oral administration of green tea or caffeine to SKH-1 mice for 2 weeks prior to a single application of UVB enhanced UVB-induced increases in the number of p53-positive cells, p21(WAF1/CIP1)-positive cells, and apoptotic sunburn cells in the epidermis. In the present study, we found that topical application of caffeine, a major chemopreventive agent in tea, to the dorsal skin of SKH-1 mice immediately after irradiation with UVB (30 mJ/cm2) enhanced UVB-induced apoptosis as measured by the number of morphologically distinct epidermal apoptotic sunburn cells and the number of caspase 3-positive cells. Time course studies indicated that UVB-induced increases in apoptotic sunburn cells were correlated with elevated levels of caspase 3, a key protease that becomes activated during an early stage of apoptosis. Topical application of caffeine immediately after UVB enhanced UVB-induced increases in caspase 3 (active form)-immunoreactive-positive cells and in caspase 3 enzyme activity in the epidermis. Topical application of caffeine had only a small stimulatory effect on UVB-induced increases in the level of wild-type p53 protein and these changes were not related temporally to caffeine-induced increases in apoptotic cells. There was little or no effect of topical applications of caffeine on epidermal cell proliferation as determined by bromodeoxyuridine (BrdU) incorporation into DNA. Topical application of (-)-epigallocatechin gallate (EGCG) to the dorsal skin of mice immediately after irradiation with UVB had a small inhibitory effect on UVB-induced increases in BrdU-positive cells in the basal layer of the epidermis, but this treatment had no effect on UVB-induced increases in apoptotic sunburn cells. The results of this study indicate a proapoptotic effect of topical application of caffeine on UVB-irradiated mouse skin.

  3. Inhibitory effect of topical application of a green tea polyphenol fraction on tumor initiation and promotion in mouse skin.

    PubMed

    Huang, M T; Ho, C T; Wang, Z Y; Ferraro, T; Finnegan-Olive, T; Lou, Y R; Mitchell, J M; Laskin, J D; Newmark, H; Yang, C S

    1992-06-01

    A green tea polyphenol fraction was evaluated for its ability to inhibit tumor initiation by polycyclic aromatic hydrocarbons and tumor promotion by a phorbol ester in the skin of CD-1 mice. Topical application of the green tea polyphenol fraction inhibited benzo[a]pyrene- and 7,12-dimethylbenz[a]-anthracene-induced tumor initiation as well as 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion. Topical application of the green tea polyphenol fraction also inhibited TPA-induced inflammation, ornithine decarboxylase activity, hyperplasia and hydrogen peroxide formation. Studies with individual polyphenolic compounds in green tea indicated that topical application of (-)-epigallocatechin gallate, (-)-epigallocatechin and (-)-epicatechin gallate inhibited TPA-induced inflammation in mouse epidermis.

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

    USGS Publications Warehouse

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

    2016-01-01

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

  5. Evaluation of carcinogenic effect of jute batching oil (JBO-P) fractions following topical application to mouse skin.

    PubMed

    Agarwal, R; Shukla, Y; Kumar, S; Mehrotra, N K

    1988-01-01

    Jute batching oil (JBO-P), a mineral oil fraction used in the processing of jute fibers, was, as reported in our earlier studies, found to be tumorigenic following repeated topical application to mouse skin. In the present investigation an attempt has been made to identify the carcinogenic constituents of this oil. The JBO was fractionated into (1) PAH free fraction, (2) fraction containing two- and three-ring PAHs and (3) more than three-ring PAH fractions by an enrichment procedure. These three JBO fractions along with unfractionated and reconstituted oil were then subjected to the in vivo assay of complete carcinogenic activity of JBO-P and its fractions following its topical application to mouse skin. The results showed that only unfractionated and reconstituted JBO-P samples per se were able to produce benign skin tumours, while all the other three fractions, i.e. PAH-free fraction, two- and three-ring PAH-containing fraction and more than three-ring PAH-containing fraction failed to produce tumours up to 40 weeks after application. In an extended study, mice belonging to the groups exposed to various fractions of JBO were promoted with 12-O-tetradecanoyl phorbol-13-acetate (TPA), a potent skin tumour promoter, for the two stage initiation-promotion protocol for skin carcinogenesis. After 14 weeks of promotion with TPA, all the surviving animals exposed to the fraction having more than three-ring PAHs developed benign tumours on their backs, while the other two fractions failed to do so.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    PubMed

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

    2005-08-01

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

  7. Topical calcitriol prior to photodynamic therapy enhances treatment efficacy in non-melanoma skin cancer mouse models

    NASA Astrophysics Data System (ADS)

    Rollakanti, Kishore; Anand, Sanjay; Maytin, Edward V.

    2015-03-01

    Non-melanoma skin cancers (NMSCs) such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common form of human cancer worldwide, and their incidence is increasing. Photodynamic therapy (PDT), mediated by topically applied aminolevulinic acid (ALA) and subsequent exposure to light (either a laser or a noncoherent source), is being increasingly used for the treatment of dermatological disorders, including BCC and SCC. However, therapeutic responses of NMSCs to ALA-PDT are currently not superior to standard therapies, although the latter have undesirable side effects including scarring. In this study, we report that preconditioning of skin tumors with calcitriol (active form of Vitamin D; Vit D) prior to ALA-PDT, significantly improves the treatment outcome. In BCC and UVB-induced SCC mouse models, we identified an increase in tumor-specific accumulation of ALA induced photosensitizer (protoporphyrin IX, PpIX) due to Vit D preconditioning, of up to 6- fold in vivo. In addition, increased expression of differentiation (145 fold, p < 0.02) and proliferation (42 fold, p <0.005) markers were identified in BCC tumors, all leading to increased tumor destruction (18.3 fold, p < 0.03) with the combination approach, as compared to ALA-PDT alone. Histomorphological changes identified using hematoxylin and eosin staining, and results of TUNEL staining, together documented a beneficial effect of Vit D pretreatment upon tumor cell death. We conclude that this new combination approach with Vit D and ALA-PDT has great potential to achieve complete remission of NMSC tumors, with excellent cosmetic results and an overall beneficial impact upon patient care.

  8. Topical gene silencing by iontophoretic delivery of an antisense oligonucleotide-dendrimer nanocomplex: the proof of concept in a skin cancer mouse model

    NASA Astrophysics Data System (ADS)

    Venuganti, , Venkata Vamsi K.; Saraswathy, Manju; Dwivedi, Chandradhar; Kaushik, Radhey S.; Perumal, Omathanu P.

    2015-02-01

    The study was aimed at investigating the feasibility of using a poly (amidoamine) (PAMAM) dendrimer as a carrier for topical iontophoretic delivery of an antisense oligonucleotide (ASO). Bcl-2, an anti-apoptotic protein implicated in skin cancer, was used as the model target protein to demonstrate the topical gene silencing approach. Confocal laser scanning microscopy studies demonstrated that the iontophoretically delivered ASO-dendrimer complex can reach the viable epidermis in porcine skin. In contrast, passively delivered free or dendrimer complexed ASO was mainly localized to the stratum corneum. The cell uptake of ASO was significantly enhanced by the dendrimer complex and the complex suppressed Bcl-2 levels in the cell. In the skin cancer mouse model, the iontophoretically delivered ASO-dendrimer complex reduced the tumor volume by 45% and was consistent with the reduction in Bcl-2 protein levels. The iontophoretically delivered ASO-dendrimer complex caused significant apoptosis in skin tumor. Overall, the findings from this study demonstrate that dendrimers are promising nanocarriers for developing topical gene silencing approaches for skin diseases.The study was aimed at investigating the feasibility of using a poly (amidoamine) (PAMAM) dendrimer as a carrier for topical iontophoretic delivery of an antisense oligonucleotide (ASO). Bcl-2, an anti-apoptotic protein implicated in skin cancer, was used as the model target protein to demonstrate the topical gene silencing approach. Confocal laser scanning microscopy studies demonstrated that the iontophoretically delivered ASO-dendrimer complex can reach the viable epidermis in porcine skin. In contrast, passively delivered free or dendrimer complexed ASO was mainly localized to the stratum corneum. The cell uptake of ASO was significantly enhanced by the dendrimer complex and the complex suppressed Bcl-2 levels in the cell. In the skin cancer mouse model, the iontophoretically delivered ASO-dendrimer complex

  9. Delivery of hydrocortisone from liposomal suspensions to the hairless mouse skin following topical application under non-occlusive and occlusive conditions.

    PubMed

    Kim, M K; Chung, S J; Lee, M H; Shim, C K

    1998-01-01

    The in-vivo cutaneous absorption of hydrocortisone was examined following topical application of hydrocortisone-containing liposomes. The formulation was applied onto the skin (1.0 cm2) of the hairless mouse (at a dose of 0.1 mg hydrocortisone) in the presence and absence of occlusion, and temporal profiles of the drug in the skin (stratum corneum and viable skin) were monitored. Under the non-occluded condition, the drug amount in the stratum corneum and viable skin reached its maximum within 1 h, and then decreased rapidly. Gelation of the liposomes by complete dehydration of the formulation under non-occlusion, which may prevent partition of the drug into the skin, appears to be a cause of the rapid decrease. Under the occluded condition, the drug amount in the skin was sustained although it then decreased dramatically compared with that under the non-occlusion (i.e. approximately 1/22 for stratum corneum and 1/8 for viable skin at 1 h, for example). A prevention of gelation of the liposomes by occlusion appears to be a potential mechanism of the maintenance of the drug concentration in the skin. The dramatic decrease in drug content in the skin may be attributed to the reduced partition of hydrocortisone, a hydrophobic drug, from the liposomes into the hydration-maintained stratum corneum under occlusion. In both application conditions, the concentration of hydrocortisone in the hydrophilic viable skin layer was markedly lower than that in the stratum corneum, indicating that partitioning between these tissues is a primary determinant of hydrocortisone reaching viable skin tissue. The estimated penetration depth of the drug into the stratum corneum was not affected significantly by the application conditions. These results demonstrate that excessive dehydration (non-occlusion) is not desirable for the prolonged delivery of hydrocortisone from liposomes into the skin. They also indicate that either hydration of the dosed skin (occlusion) is not preferable for

  10. Overexpression of CRABPI in suprabasal keratinocytes enhances the proliferation of epidermal basal keratinocytes in mouse skin topically treated with all-trans retinoic acid

    SciTech Connect

    Tang, X.-H.; Vivero, Marina; Gudas, Lorraine J.

    2008-01-01

    We investigated whether ectopic expression of CRABPI, a cellular retinoic acid binding protein, influenced the actions of all-trans retinoic acid (ATRA) in transgenic (TG) mice. We targeted CRABPI to the basal vs. suprabasal layers of mouse epidermis by using the keratin 14 (K14) and keratin 10 (K10) promoters, respectively. Greater CRABPI protein levels were detected in the epidermis of adult transgenic(+) mice than in transgenic(-) mice for both transgenes. In adult mouse skin CRABPI overexpression in the basal or suprabasal keratinocytes did not cause morphological abnormalities, but did result in decreased CRABPII mRNA levels. Ectopically overexpressed CRABPI in suprabasal keratinocytes, but not in basal keratinocytes, enhanced the thickening of the epidermis induced by topical ATRA treatments (10 {mu}M, 400 {mu}l for 4 days) by 1.59 {+-} 0.2-fold (p < 0.05). ATRA treatment (10 {mu}M) resulted in a 59.9 {+-} 9.8% increase (p < 0.05) in the BrdU labeling index in K10/FLAG-CRABPI TG(+) mice vs. TG(-) mice. Retinoid topical treatments reduced p27 and CYP26A1 mRNA levels in TG(+) and TG(-) mouse skin in K14 and K10/FLAG-CRABPI transgenic mice. As epidermal basal keratinocyte proliferation is stimulated by paracrine growth factors secreted by ATRA activated suprabasal keratinocytes, our results indicate that CRABPI overexpression in suprabasal keratinocytes enhances the physiological functions of ATRA.

  11. Topical Steroid-Damaged Skin

    PubMed Central

    Abraham, Anil; Roga, Gillian

    2014-01-01

    Topical steroids, commonly used for a wide range of skin disorders, are associated with side effects both systemic and cutaneous. This article aims at bringing awareness among practitioners, about the cutaneous side effects of easily available, over the counter, topical steroids. This makes it important for us as dermatologists to weigh the usefulness of topical steroids versus their side effects, and to make an informed decision regarding their use in each individual based on other factors such as age, site involved and type of skin disorder. PMID:25284849

  12. Clearance of protoporphyrin IX from mouse skin after topical application of 5-aminolevulinic acid and its methyl ester

    NASA Astrophysics Data System (ADS)

    Juzenas, Petras; Sorensen, Roar; Iani, Vladimir; Moan, Johan

    1999-02-01

    The clearance of protoporphyrin IX (PpIX) from the skin of hairless BALB/c mice after topical application of 5- aminolevulinic acid (ALA) and its methyl ester (ALA-Me) was investigated. Creams containing 2 or 20% of ALA or ALA-Me were topically applied on spots of approximately 1 cm2 for 12 hours. The PpIX fluorescence was detected by the means of a Perkin Elmer LS50B luminescence spectrometer equipped with a fiber-optic probe. The emission spectrum was identical with that of cell-bound PpIX. After 12 hours application of ALA and ALA-Me similar amounts of PpIX were found. After creme removal the ALA-induced PpIX fluorescence decayed with a half-life of about 20 hours (20% ALA cream). The ALA-Me-induced PpIX was faster cleared from the skin than ALA-induced PpIX, and had a half-life of about 7 hours (20% ALA-Me cream).

  13. Formation of protoporphyrin IX in mouse skin after topical application of 5-aminolevulinic acid and its methyl esther

    NASA Astrophysics Data System (ADS)

    Sorensen, Roar; Juzenas, Petras; Iani, Vladimir; Moan, Johan

    1999-02-01

    Normal skin of nude mice (Balb/c) was treated topically with 5-aminolevulinic acid (ALA) and its methyl ester (ALA-Me) for 24 hours. Approximately 0.1 gram of freshly prepared cream was applied to a spot of 1 cm2 on the flank of the mice, which was then covered with a transparent dressing. The ALA induced protoporphyrin IX (PpIX) was studied by means of a noninvasive fiber-optic fluorescence probe connected to a luminescence spectrometer. The excitation wavelength was 407 nm, and the emission wavelength was 637 nm. For the first hour a slight lag in PpIX production was observed for the mice treated with ALA-Me compared to the mice treated with ALA. After approximately 12 hours the ALA and the ALA-Me treated mice showed the same PpIX fluorescence intensity. From 12 hours until 24 hours the PpIX fluorescence intensity decreased for both treatment modalities, even though ALA and ALA-Me were continuously present. At 24 hours ALA-Me-treated mice had less than half the amount of PpIX in their skin compared with ALA- treated mice.

  14. Drug and vehicle deposition from topical applications: localization of minoxidil within skin strata of the hairless mouse.

    PubMed

    Tsai, J C; Weiner, N; Flynn, G L; Ferry, J J

    1994-01-01

    The cutaneous bioavailability of topical 2% minoxidil solution was verified in live hairless mice. Minoxidil and propylene glycol deposition on the skin surface, epidermis and dermis from the single-dose in vivo study were compared with the results from previous in vitro studies. A distinct difference is apparent in the epidermis where the in vitro values are 11-22 times higher than the in vivo values for minoxidil and 8-16 times higher for propylene glycol. The differences were not as great in the dermis. Percutaneous absorption of the drug appeared to be a very small fraction of the applied dose. Similarly shaped stratum corneum and plasma concentration profiles and the relatively constant dermal profiles of minoxidil and propylene glycol open the possibility of transappendageal routes being involved in percutaneous absorption. The greater amount of drug and vehicle found in the dermis from in vitro studies can be explained by the absence of dermal clearance. The overestimation in the amount of drug found in the epidermis in vitro may also be attributable to poor dermal clearance. On the whole, the study raises questions about the use of in vitro tissue dispositions for bioavailability assessment and bioequivalence demonstration. PMID:8054208

  15. Vulvar Skin Atrophy Induced by Topical Glucocorticoids

    PubMed Central

    Johnson, Elisabeth; Groben, Pamela; Eanes, Alisa; Iyer, Priya; Ugoeke, Joseph; Zolnoun, Denniz

    2011-01-01

    Steroid induced skin atrophy is the most frequent and perhaps most important cutaneous side effect of topical glucocorticoid therapy. To date, it has not been described in vulvar skin. We describe a patient with significant vulvar skin atrophy following prolonged steroid application to treat vulvar dermatitis. The extensive atrophy in the perineum resulted in secondary ‘webbing’ and partial obstruction of genital hiatus and superimposed dyspareunia. Prolonged topical steroids may result in atrophic changes in vulvar skin. Therefore, further research in clinical correlates of steroid-induced atrophy in the vulvar region is warranted. PMID:22594868

  16. Systemic and topical drugs for aging skin.

    PubMed

    Kockaert, Michael; Neumann, Martino

    2003-08-01

    The rejuvenation of aging skin is a common desire for our patients, and several options are available. Although there are some systemic methods, the most commonly used treatments for rejuvenation of the skin are applied topically. The most frequently used topical drugs include retinoids, alpha hydroxy acids (AHAs), vitamin C, beta hydroxy acids, anti-oxidants, and tocopherol. Combination therapy is frequently used; particularly common is the combination of retinoids and AHAs. Systemic therapies available include oral retinoids and vitamin C. Other available therapies such as chemical peels, face-lifts, collagen, and botulinum toxin injections are not discussed in this article. PMID:12884471

  17. 32P-postlabeling and HPLC separation of DNA adducts formed by diesel exhaust extracts in vitro and in mouse skin and lung after topical treatment.

    PubMed

    Savela, K; King, L; Gallagher, J; Lewtas, J

    1995-09-01

    Diesel exhaust extracts contain many carcinogenic compounds which have been shown to form polycyclic aromatic hydrocarbon (PAH)- and nitrated PAH-DNA adducts in rodent skin and lung. The aim of this study was to characterize by 32P-postlabeling, TLC and HPLC the primary postlabeled PAH-DNA adduct(s) formed in vitro and in vivo by diesel extracts. The diesel particle extracts had known concentrations of benzo[a]pyrene, benzo[b,j,k]-fluoranthenes (B[b,j,k]F) and chrysene. DNA adducts were analyzed in calf thymus DNA incubated in vitro with PAHs activated by S9 mix and in skin and lung DNA from topically treated mice. The main diesel-derived DNA adduct formed in vitro and in vivo did not co-migrate on HPLC and large TLC plates with (+/-)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti BPDE)-, B[b]F-,B[j]F-,B[k]F-or chrysene-DNA adduct standards. By co-chromatography DNA adducts formed by chrysene from both in vitro and in vivo samples were identified. Nissan diesel extract containing higher PAH concentrations than Volkswagen automobile extract formed skin DNA adducts that co-migrated with chrysene- and anti BPDE- DNA-derived adducts. We conclude that the use of a highly sensitive 32P-postlabeling method combined with HPLC improves the identification of PAH adducts formed by complex mixtures such as diesel exhaust extracts.

  18. 32P-postlabeling and HPLC separation of DNA adducts formed by diesel exhaust extracts in vitro and in mouse skin and lung after topical treatment.

    PubMed

    Savela, K; King, L; Gallagher, J; Lewtas, J

    1995-09-01

    Diesel exhaust extracts contain many carcinogenic compounds which have been shown to form polycyclic aromatic hydrocarbon (PAH)- and nitrated PAH-DNA adducts in rodent skin and lung. The aim of this study was to characterize by 32P-postlabeling, TLC and HPLC the primary postlabeled PAH-DNA adduct(s) formed in vitro and in vivo by diesel extracts. The diesel particle extracts had known concentrations of benzo[a]pyrene, benzo[b,j,k]-fluoranthenes (B[b,j,k]F) and chrysene. DNA adducts were analyzed in calf thymus DNA incubated in vitro with PAHs activated by S9 mix and in skin and lung DNA from topically treated mice. The main diesel-derived DNA adduct formed in vitro and in vivo did not co-migrate on HPLC and large TLC plates with (+/-)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti BPDE)-, B[b]F-,B[j]F-,B[k]F-or chrysene-DNA adduct standards. By co-chromatography DNA adducts formed by chrysene from both in vitro and in vivo samples were identified. Nissan diesel extract containing higher PAH concentrations than Volkswagen automobile extract formed skin DNA adducts that co-migrated with chrysene- and anti BPDE- DNA-derived adducts. We conclude that the use of a highly sensitive 32P-postlabeling method combined with HPLC improves the identification of PAH adducts formed by complex mixtures such as diesel exhaust extracts. PMID:7554058

  19. Topically applied ceramide accumulates in skin glyphs

    PubMed Central

    Zhang, Qihong; Flach, Carol R; Mendelsohn, Richard; Mao, Guangru; Pappas, Apostolos; Mack, M Catherine; Walters, Russel M; Southall, Michael D

    2015-01-01

    Ceramides (CERs), structural components of the stratum corneum (SC), impart essential barrier properties to this thin outer layer of the epidermis. Variations in CER species within this layer have been linked to several skin diseases. A recent proliferation of CER-containing topical skin-care products warrants the elucidation of CER penetration profiles in both healthy and diseased skin. In the current study, the spatial distributions of CER concentration profiles, following topical application of two species of CER, were tracked using infrared imaging. Suspensions of single-chain perdeuterated sphingosine and phytosphingosine CER in oleic acid were applied, in separate experiments, to the surface of healthy intact ex vivo human skin using Franz diffusion cells. Following either a 24- or 48-hour incubation period at 34°C, infrared images were acquired from microtomed skin sections. Both CER species accumulated in glyph regions of the skin and penetrated into the SC, to a limited extent, only in these regions. The concentration profiles observed herein were independent of the CER species and incubation time utilized in the study. As a result, a very heterogeneous, sparse, spatial distribution of CERs in the SC was revealed. In contrast, oleic acid was found to be fairly homogeneously distributed throughout the SC and viable epidermis, albeit at lower concentrations in the latter. A more uniform, lateral distribution of CERs in the SC would likely be important for barrier efficacy or enhancement. PMID:26170709

  20. Topical Application of a Platelet Activating Factor Receptor Agonist Suppresses Phorbol Ester-Induced Acute and Chronic Inflammation and Has Cancer Chemopreventive Activity in Mouse Skin

    PubMed Central

    Ocana, Jesus A.; DaSilva-Arnold, Sonia C.; Bradish, Joshua R.; Richey, Justin D.; Warren, Simon J.; Rashid, Badri; Travers, Jeffrey B.; Konger, Raymond L.

    2014-01-01

    Platelet activating factor (PAF) has long been associated with acute edema and inflammatory responses. PAF acts by binding to a specific G-protein coupled receptor (PAF-R, Ptafr). However, the role of chronic PAF-R activation on sustained inflammatory responses has been largely ignored. We recently demonstrated that mice lacking the PAF-R (Ptafr-/- mice) exhibit increased cutaneous tumorigenesis in response to a two-stage chemical carcinogenesis protocol. Ptafr-/- mice also exhibited increased chronic inflammation in response to phorbol ester application. In this present study, we demonstrate that topical application of the non-hydrolysable PAF mimetic (carbamoyl-PAF (CPAF)), exerts a potent, dose-dependent, and short-lived edema response in WT mice, but not Ptafr -/- mice or mice deficient in c-Kit (c-KitW-sh/W-sh mice). Using an ear inflammation model, co-administration of topical CPAF treatment resulted in a paradoxical decrease in both acute ear thickness changes associated with a single PMA application, as well as the sustained inflammation associated with chronic repetitive PMA applications. Moreover, mice treated topically with CPAF also exhibited a significant reduction in chemical carcinogenesis. The ability of CPAF to suppress acute and chronic inflammatory changes in response to PMA application(s) was PAF-R dependent, as CPAF had no effect on basal or PMA-induced inflammation in Ptafr-/- mice. Moreover, c-Kit appears to be necessary for the anti-inflammatory effects of CPAF, as CPAF had no observable effect in c-KitW-sh/W-sh mice. These data provide additional evidence that PAF-R activation exerts complex immunomodulatory effects in a model of chronic inflammation that is relevant to neoplastic development. PMID:25375862

  1. A pharmacokinetic study of a topical anesthetic (EMLA® ) in mouse soft tissue laceration.

    PubMed

    Al-Musawi, Alaa; Matar, Kamal; Kombian, Samuel B; Andersson, Lars

    2012-12-01

    The use of topical anesthesia instead of injection of local anesthetics for managing soft tissue lacerations in the emergency situations may be a relief for both patients and surgeons. Topical anesthesia in the form of a cream eutectic mixture of local anesthetics (EMLA®) containing 2.5% lidocaine and 2.5% prilocaine has been reported as an efficient anesthetic on skin before venipuncture anesthesia and as an alternative to injection anesthesia in some minor surgery situations. The aim of this study was to compare the pharmacokinetics of EMLA® when applied in a laceration with topical skin application in the mouse. A total of 120 Albino Laboratory-bred strain mouse (BALB-c) male mice were divided into three groups with regard to application mode of EMLA®. Group A: with laceration, 48 mice; Group B: on intact shaved skin, 48 mice; Group C: control group (24 mice) with same procedures but without application of EMLA®. Blood levels were collected at 0, 10, 20, 30, 45, 60, 75, and 90 min post-EMLA® application. Plasma sample analysis was carried out by employing liquid chromatography coupled with tandem mass spectrometric (LC-MS/MS) method, and the pharmacokinetic analysis of the mouse plasma samples was estimated by standard non-compartmental methods. The pharmacokinetic parameters of lidocaine and prilocaine were significantly altered following EMLA® application to lacerated mouse skin in contrast to intact skin. The absorption of lidocaine and prilocaine was rapid following application of EMLA® to lacerated and intact mouse skin. Maximum drug plasma concentration (C(max) ) and area under the drug plasma concentration-time curve (AUC) values of lidocaine were significantly increased by 448.6% and 161.5%, respectively, following application of EMLA to lacerated mouse skin in comparison with intact mouse skin. Similarly, prilocaine's C(max) and AUC values were also increased by 384% and 265.7%, respectively, following EMLA application to lacerated mouse skin, in

  2. Topical hypochlorite ameliorates NF-κB–mediated skin diseases in mice

    PubMed Central

    Leung, Thomas H.; Zhang, Lillian F.; Wang, Jing; Ning, Shoucheng; Knox, Susan J.; Kim, Seung K.

    2013-01-01

    Nuclear factor-κB (NF-κB) regulates cellular responses to inflammation and aging, and alterations in NF-κB signaling underlie the pathogenesis of multiple human diseases. Effective clinical therapeutics targeting this pathway remain unavailable. In primary human keratinocytes, we found that hypochlorite (HOCl) reversibly inhibited the expression of CCL2 and SOD2, two NF-κB–dependent genes. In cultured cells, HOCl inhibited the activity of inhibitor of NF-κB kinase (IKK), a key regulator of NF-κB activation, by oxidizing cysteine residues Cys114 and Cys115. In NF-κB reporter mice, topical HOCl reduced LPS-induced NF-κB signaling in skin. We further evaluated topical HOCl use in two mouse models of NF-κB–driven epidermal disease. For mice with acute radiation dermatitis, topical HOCl inhibited the expression of NF-κB–dependent genes, decreased disease severity, and prevented skin ulceration. In aged mice, topical HOCl attenuated age-dependent production of p16INK4a and expression of the DNA repair gene Rad50. Additionally, skin of aged HOCl-treated mice acquired enhanced epidermal thickness and proliferation, comparable to skin in juvenile animals. These data suggest that topical HOCl reduces NF-κB–mediated epidermal pathology in radiation dermatitis and skin aging through IKK modulation and motivate the exploration of HOCl use for clinical aims. PMID:24231355

  3. Skin permeation of 5-methoxypsoralen from topical dosage forms.

    PubMed

    Colombo, Gaia; Artusi, Mariella; Santi, Patrizia; Colombo, Paolo; Bettini, Ruggero; Zucchi, Alfredo; Nicoli, Sara

    2003-02-01

    The topical photochemotherapy of dermatoses with psoralens (PUVA therapy) requires an adequate drug level at the target site (basal epidermis) at the time of UVA radiation. The aim of this work was to enhance 5-methoxypsoralen transport to the basal epidermis, with the goal to shorten the delay between drug application and UVA irradiation. 5-Methoxypsoralen transport through rabbit skin was studied in vitro from topical formulations (water solution, gel. and emulsion). The results obtained show that the use of the emulsion increased the flux through rabbit ear skin, even if partitioning was not favorable. Additionally, the time lag was sensibly reduced, compared with the gel and solution. Furthermore, drug accumulation in human skin in vitro was determined using the thin slicing technique. Human skin accumulation profile was significantly higher for the emulsion, compared with the gel, indicating that the delay between psoralen application and UVA irradiation can be shortened.

  4. Skin permeation and antinociception of topical gabapentin formulations.

    PubMed

    Bryson, Evan; Asbill, Scott; Sweitzer, Sarah

    2014-01-01

    Chronic pain affects greater than 116 million Americans each year. Even with the best pain management approaches, many chronic pain patients still suffer from moderate to severe pain. An alternative therapy to treat chronic pain includes compounded topical formulations of common analgesics. Compounded dosage forms of gabapentin are commonly used for pain management, however, the penetration and efficacy of gabapentin in these compounded topical formulations has not been fully studied. In this study, the transdermal penetration of gabapentin was studied in Franz diffusion cells using porcine skin. Gabapentin was compounded in two commercially available bases; Lipobase, Lipoderm, and a standard poloxamer lecithin organogel. The penetration and retention of gabapentin in the skin was dependent upon the base. The most rapid and greatest penetration and retention of gabapentin in the skin occurred with a poloxamer lecithin organogel base. Lipobase and Lipoderm bases produced slow and smaller penetration and retention of gabapentin as compared to poloxamer lecithin organogel base. Gabapentin 1% and 5% compounded in Lipoderm were tested in the in vivo preclinical formalin pain model. Topical 5% gabapentin produced a similar reduction in nociception in both Phase 1 and Phase 2 of the formalin response as systemic subcutaneous gabapentin (100 mg/kg). Topical 1% gabapentin reduced Phase 2, but not Phase 1 formalin-induced nociceptive behaviors. These findings suggest that topical administration of gabapentin may produce local antinociception.

  5. Emollients: application of topical treatments to the skin.

    PubMed

    Dunning, Gail

    Nurses working in various clinical settings can make a real difference to the clinical effectiveness of topical applications to the skin by increasing their knowledge of the choice and mechanisms involved. This is particularly the case for nurses who are non-medical prescribers when considering first-line therapies for patients with eczema. It is important for all nurses to acknowledge that topical treatments, however simple, are a form of drug therapy and must be given the same considerations for their specific actions whether you are prescribing, applying or reviewing their effect. Emollients have an as important part to play in the treatment of all dry skin conditions. This article focuses on increasing the reader's knowledge of the application of topical emollient therapy, as well as highlighting some practical tips to consider.

  6. Effect of topically applied tocopherol on ultraviolet radiation-mediated free radical damage in skin.

    PubMed

    Jurkiewicz, B A; Bissett, D L; Buettner, G R

    1995-04-01

    Previously, we demonstrated by electron paramagnetic resonance (EPR) spectroscopy that ultraviolet radiation induces free-radical formation in Skh-1 hairless mouse skin. Because free-radical oxidative stress is thought to play a principal role in skin photoaging and cancer, oxidative stress and subsequent photodamage should be decreased by supplementation of skin with antioxidants. Using both the ascorbate free radical and an EPR spin-trapping system to detect short-lived radicals, we evaluated the effect of the topically applied antioxidants tocopherol sorbate, alpha-tocopherol, and tocopherol acetate on ultraviolet radiation-induced free-radical formation. We show that tocopherol sorbate significantly decreases the ultraviolet radiation-induced radical flux in skin. With our chronically exposed mouse model, tocopherol sorbate was also found to be significantly more protective against skin photoaging than alpha-tocopherol and tocopherol acetate. These results extend our previous observations of ultraviolet radiation-induced free-radical generation in skin and indicate the utility of tocopherol sorbate as an antioxidant in providing significant protection against ultraviolet radiation-induced oxidative damage.

  7. Development of a Topical Treatment for Psoriasis Targeting RORγ: From Bench to Skin

    PubMed Central

    Takeda, Yukimasa; Bui, Thi; Neil, Jessica; Rickard, David; Millerman, Elizabeth; Therrien, Jean-Philippe; Nicodeme, Edwige; Brusq, Jean-Marie; Birault, Veronique; Viviani, Fabrice; Hofland, Hans; Jetten, Anton M.; Cote-Sierra, Javier

    2016-01-01

    Background Psoriasis is a chronic inflammatory skin disorder involving marked immunological changes. IL-17-targeting biologics have been successful in reducing the disease burden of psoriasis patients with moderate-to-severe disease. Unfortunately, the stratum corneum prevents penetration of large molecule weight proteins, including monoclonal antibodies. Thus, for the majority of psoriasis patients ineligible for systemic treatments, a small molecule targeting RORγt, the master regulator of IL-17 family cytokines, may represent an alternative topical medicine with biologic-like efficacy. Methods and Findings The preclinical studies described in this manuscript bridge the gap from bench to bedside to provide the scientific foundation for a compound entering clinical trials for patients with mild to moderate psoriasis. In addition to several ex vivo reporter assays, primary T cell cultures, and the imiquimod mouse model, we demonstrate efficacy in a newly developed human ex vivo skin assay, where Th17-skewed cytokine expression is induced from skin-resident immune cells. Importantly, the skin barrier remains intact allowing for the demonstration of topical drug delivery. With the development of this novel assay, we demonstrate potent compound activity in the target tissue: human skin. Finally, target engagement by this small molecule was confirmed in ex vivo lesional psoriatic skin. Conclusions Our work describes a progressive series of assays to demonstrate the potential clinical value of a novel RORγ inverse agonist small molecule with high potency and selectivity, which will enter clinical trials in late 2015 for psoriasis patients. PMID:26870941

  8. Modern approach to topical treatment of aging skin.

    PubMed

    Puizina-Ivić, Neira; Mirić, Lina; Carija, Antoanela; Karlica, Dobrila; Marasović, Dujomir

    2010-09-01

    The main processes involved in skin aging are intrinsic and extrinsic. Apart from them, so called stochastic aging connotes cell damage caused by metabolic processes, free radicals and cosmic irradiation. The clinical expression of intrinsic aging include smooth, dry, and thinned skin with accentuated expression lines. It is inevitable and time dependent. Extrinsically aged skin shows signs of photodamage which include appearance of wrinkles, pigmented lesions, actinic keratoses and patchy hypopigmentations. Therapeutic modalities imply photoprotection with sunscreens that prevent sunburns and block ultraviolet irradiation. Other modalities include use of retinoids which regulate gene transcription with subsequent cellular differentiation and proliferation. The topical and peroral administration of network antioxidants, such as vitamin E and C, coenzyme Q10, alpha-lipoic acid and glutathione, enhance antiaging effect. The other antioxidants such as green tea, dehydroepiandrosterone, melatonin, selenium and resveratrol, have also antiaging and anti-inflammatory effects. Topical bleaching agents such as hydroquinone, kojic acid and azelaic acid can reduce signs of aging. Studies confirm the efficacy of these topical agents in combination with superficial and/or medium depth or deep peeling agents for photodamaged skin treatment. Indications for type of chemical peels according to various clinical diagnosis are done, as well as advantages and disadvantages of different types of chemical peels. PMID:20977120

  9. Modern approach to topical treatment of aging skin.

    PubMed

    Puizina-Ivić, Neira; Mirić, Lina; Carija, Antoanela; Karlica, Dobrila; Marasović, Dujomir

    2010-09-01

    The main processes involved in skin aging are intrinsic and extrinsic. Apart from them, so called stochastic aging connotes cell damage caused by metabolic processes, free radicals and cosmic irradiation. The clinical expression of intrinsic aging include smooth, dry, and thinned skin with accentuated expression lines. It is inevitable and time dependent. Extrinsically aged skin shows signs of photodamage which include appearance of wrinkles, pigmented lesions, actinic keratoses and patchy hypopigmentations. Therapeutic modalities imply photoprotection with sunscreens that prevent sunburns and block ultraviolet irradiation. Other modalities include use of retinoids which regulate gene transcription with subsequent cellular differentiation and proliferation. The topical and peroral administration of network antioxidants, such as vitamin E and C, coenzyme Q10, alpha-lipoic acid and glutathione, enhance antiaging effect. The other antioxidants such as green tea, dehydroepiandrosterone, melatonin, selenium and resveratrol, have also antiaging and anti-inflammatory effects. Topical bleaching agents such as hydroquinone, kojic acid and azelaic acid can reduce signs of aging. Studies confirm the efficacy of these topical agents in combination with superficial and/or medium depth or deep peeling agents for photodamaged skin treatment. Indications for type of chemical peels according to various clinical diagnosis are done, as well as advantages and disadvantages of different types of chemical peels.

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

    PubMed

    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 (<7%) either at an infinite 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

  11. Do lasers or topicals really work for nonmelanoma skin cancers?

    PubMed

    Brightman, Lori; Warycha, Melanie; Anolik, Robert; Geronemus, Roy

    2011-03-01

    Novel strategies are urgently needed to address the millions of nonmelanoma skin cancers treated in the United States annually. The need is greatest for those patients who are poor surgical candidates or those prone to numerous nonmelanoma skin cancers and therefore at risk for marked disfigurement. Traditional treatment strategies include electrosurgery with curettage, radiation therapy, cryotherapy, excision, and Mohs micrographic surgery. Alternatives to traditional treatment, including topical medications and light or laser therapies, are becoming popular; however, there are various degrees of efficacy among these alternative tactics. These alternatives include topical retinoids, peels, 5-fluorouracil, imiquimod, photodynamic therapy, and lasers. The purpose of this paper is to review the available data regarding these alternative strategies and permit the reader to have a sense of which therapies are reasonable options for care. PMID:21540017

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

    PubMed

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

    2013-03-01

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

  13. Failure of topical acyclovir in ointment to penetrate human skin.

    PubMed Central

    Freeman, D J; Sheth, N V; Spruance, S L

    1986-01-01

    Topical acyclovir (ACV) in polyethylene glycol (PEG) ointment has been disappointing in the treatment of recurrent herpes simplex virus infections in immunocompetent patients. To investigate the possible role of poor drug delivery from this formulation, we studied the penetration of ACV through excised human skin from three vehicles; PEG ointment, modified aqueous cream, and dimethyl sulfoxide. A second antiviral agent, idoxuridine, was studied in the same formulations, and drug delivery through excised guinea pig skin was also assessed for comparison. The delivery of ACV from PEG ointment was very slow for both human and guinea pig skin (drug flux, 0.055 and 0.047 microgram/cm2 per h, respectively). Formulation of ACV in modified aqueous cream and in dimethyl sulfoxide resulted in an 8- and 60-fold increase, respectively, in the flux of ACV through human skin. Idoxuridine behaved similarly to ACV in the three vehicles. The poor clinical results seen with topical use of ACV ointment may be due in part to retarded drug delivery from this formulation. PMID:3729337

  14. Hyperelastic Material Properties of Mouse Skin under Compression.

    PubMed

    Wang, Yuxiang; Marshall, Kara L; Baba, Yoshichika; Gerling, Gregory J; Lumpkin, Ellen A

    2013-01-01

    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 location maintains a

  15. Topical application of a novel, water-soluble gamma-tocopherol derivative prevents UV-induced skin damage in mice.

    PubMed

    Yasuoka, Shingo; Takata, Jiro; Karube, Yoshiharu; Katoh, Eiko; Tsuzuki, Toshi; Kizu, Junko; Tsuchiya, Masao; Kobayashi, Shizuko

    2005-01-01

    We investigated whether the topical application of a novel, water-soluble gamma-tocopherol (gamma-Toc) derivative, gamma-tocopherol-N,N-dimethylglycinate hydrochloride (gamma-TDMG), could protect against UV-induced skin damage in hairless mice. Topical pre- or post-application of a 5% (93 mM) gamma-TDMG solution in water/propylene glycol/ethanol (2:1:2) significantly prevented sunburn cell formation, lipid peroxidation and edema/inflammation that were induced by exposure to a single dose of UV irradiation of 5 kJ/m2 (290-380 nm, maximum 312 nm). This effect was greater than that seen with two alpha-Toc derivatives, alpha-tocopherol acetate (alpha-TA) and alpha-tocopherol-N,N-dimethylglycinate (alpha-TDMG). When a 5% solution of gamma-TDMG was applied to mouse skin for 1 h, cutaneous gamma-Toc increased by 25-fold after 24 h; levels of cutaneous alpha-Toc increased by only two- and eight-fold in alpha-TDMG and alpha-TA treated skins, respectively. These findings indicated that gamma-TDMG immediately converted to gamma-Toc in the skin and suggest that ability of gamma-TDMG to protect the skin from the damaging effects of irradiation was due to its conversion to gamma-Toc. When a 5% solution of gamma-Toc was applied to mouse skin for 1 h, cutaneous gamma-Toc rapidly increased by 25-fold, but fell to baseline levels by 24 h. In contrast, the concentration of gamma-Toc in skin that was treated with gamma-TDMG similarly increased, but these high levels were maintained after 24 h. These results suggest that gamma-TDMG may be a more effective source of gamma-Toc in skin. Thus, the topical application of gamma-TDMG may be efficacious for the prevention of UV-B-induced skin damage.

  16. Functional testing of topical skin formulations using an optimised ex vivo skin organ culture model.

    PubMed

    Sidgwick, G P; McGeorge, D; Bayat, A

    2016-07-01

    A number of equivalent-skin models are available for investigation of the ex vivo effect of topical application of drugs and cosmaceuticals onto skin, however many have their drawbacks. With the March 2013 ban on animal models for cosmetic testing of products or ingredients for sale in the EU, their utility for testing toxicity and effect on skin becomes more relevant. The aim of this study was to demonstrate proof of principle that altered expression of key gene and protein markers could be quantified in an optimised whole tissue biopsy culture model. Topical formulations containing green tea catechins (GTC) were investigated in a skin biopsy culture model (n = 11). Punch biopsies were harvested at 3, 7 and 10 days, and analysed using qRT-PCR, histology and HPLC to determine gene and protein expression, and transdermal delivery of compounds of interest. Reduced gene expression of α-SMA, fibronectin, mast cell tryptase, mast cell chymase, TGF-β1, CTGF and PAI-1 was observed after 7 and 10 days compared with treated controls (p < 0.05). Histological analysis indicated a reduction in mast cell tryptase and chymase positive cell numbers in treated biopsies compared with untreated controls at day 7 and day 10 (p < 0.05). Determination of transdermal uptake indicated that GTCs were detected in the biopsies. This model could be adapted to study a range of different topical formulations in both normal and diseased skin, negating the requirement for animal models in this context, prior to study in a clinical trial environment. PMID:27086034

  17. Functional testing of topical skin formulations using an optimised ex vivo skin organ culture model.

    PubMed

    Sidgwick, G P; McGeorge, D; Bayat, A

    2016-07-01

    A number of equivalent-skin models are available for investigation of the ex vivo effect of topical application of drugs and cosmaceuticals onto skin, however many have their drawbacks. With the March 2013 ban on animal models for cosmetic testing of products or ingredients for sale in the EU, their utility for testing toxicity and effect on skin becomes more relevant. The aim of this study was to demonstrate proof of principle that altered expression of key gene and protein markers could be quantified in an optimised whole tissue biopsy culture model. Topical formulations containing green tea catechins (GTC) were investigated in a skin biopsy culture model (n = 11). Punch biopsies were harvested at 3, 7 and 10 days, and analysed using qRT-PCR, histology and HPLC to determine gene and protein expression, and transdermal delivery of compounds of interest. Reduced gene expression of α-SMA, fibronectin, mast cell tryptase, mast cell chymase, TGF-β1, CTGF and PAI-1 was observed after 7 and 10 days compared with treated controls (p < 0.05). Histological analysis indicated a reduction in mast cell tryptase and chymase positive cell numbers in treated biopsies compared with untreated controls at day 7 and day 10 (p < 0.05). Determination of transdermal uptake indicated that GTCs were detected in the biopsies. This model could be adapted to study a range of different topical formulations in both normal and diseased skin, negating the requirement for animal models in this context, prior to study in a clinical trial environment.

  18. Determination of the physicochemical properties of candidate topical skin protectants

    SciTech Connect

    Hayes, T.L.; Markle, R.; Bigg, D.; Mangaraj, D.; Elhard, J.

    1993-05-13

    The U.S. Army Medical Chemical Defense Research Program has identified several topical skin protectants (TSPs), based on perfluorinated oils and polytetrafluoroethylene (PTFE) powders, for further development. These TSPs provide protection against chemical surety agents (CSAs) when applied to exposed skin areas such as hands, face, or neck. Although considerable information is available on the biological efficacy of these TSPS, little information is available on their physicochemical properties. Previous testing has demonstrated that procedural changes in formulation can dramatically alter the biological protection provided by a TSP. Physicochemical characterization of candidate TSPs is needed to ensure that the fielded formulation of a TSP is not different from the formulation that was evaluated during development. The physicochemical characterization of TSPs will also establish whether a correlation exists between physicochemical properties of a TSP and its biological efficacy. Those tests that are highly correlated with biological efficacy can then be incorporated into TSP manufacturing programs. The following procedures have been found most useful: (1) scanning electron microscopy (SEM), (2) rheology (Haake plate and cone viscometer), (3) gel permeation chromatography (GPC), and (4) water contact angle measurements (Rame Hart Goniometer).

  19. A study of the penetration of five novel synthetic steroids through hairless mouse skin in vitro.

    PubMed

    Michniak-Mikolajczak, B B; Bodor, N

    1985-08-01

    Synopsis The change in the physiochemical properties of topical corticosteroids by addition of one or more chemical substituents is probably one of the most important factors affecting the activity and bioavailability of the steroid. During work on developing new steroids five synthetic steroids were tested for their ability to pass through freshly excised hairless mouse skin placed in diffusion cells at 33 1 degrees C. Analysis of the compounds was made using high performance liquid chromatography. The presence of flourine at carbon 9, in the chemical grouping at carbon 17, or the addition of a pentyl group was found to increase the penetration of the steroid through the skin. PMID:19460025

  20. Isoflavonoid photoprotection in mouse and human skin is dependent on metallothionein.

    PubMed

    Widyarini, Sitarina; Allanson, Munif; Gallagher, Nerida L; Pedley, Julie; Boyle, Glen M; Parsons, Peter G; Whiteman, David C; Walker, Catherine; Reeve, Vivienne E

    2006-01-01

    Previous studies report that selected topical isoflavonoids are immunoprotective in both mice and humans, when applied following UV irradiation. Isoflavonoids have documented antioxidant activity, but their mechanism of immunomodulation remains unclear. This study examines whether photoimmunoprotection by the isoflavonoids might result from their interaction with one cutaneous antioxidant known to modulate UV photodamage, metallothionein (MT). In mice bearing a null mutation for MT-I and -II, we found that immunoprotection by the isoflavonoid 4',7-dihydroxyisoflavane (equol) against solar-simulated UV radiation (SSUV) or exogenous cis-urocanic acid was abrogated. Topical equol did not activate MT expression in normal mouse skin, but markedly enhanced the increase in MT expression in murine epidermis following SSUV irradiation. Normal human skin, unlike murine, expressed MT in the basal epidermis. Following SSUV irradiation, topical application of the related synthetic isoflavonoid NV-07alpha to human skin also markedly enhanced epidermal MT expression. The NV-07alpha has been reported previously to protect humans against the UV suppression of Mantoux reactions. Thus, epidermal MT expression appears to protect against photoimmunosuppression in both human and mouse skin. We speculate that equol and its related derivative NV-07alpha may activate the MT gene synergistically with SSUV, to produce the enhanced immunoprotective effect.

  1. [Magistral prepared lidocaine-gel for topical aplication on skin].

    PubMed

    Sklenár, Zbynĕk; Horácková, Katerína; Bakhouche, Hana; Slanar, Ondrej

    2012-08-01

    Due to a limited availability of industrially manufactured products containing local anesthetics for skin application and an increased demand for lidocaine-containing gel applicable prior to a product containing capsaicin for neuropathic pain treatment, it is necessary to prepare a topical semi-solid preparation containing the local anesthetic in pharmacies. Our aim was to create a mixed system of a hydrophilic gel with the emulsified drug, using excipients to decrease the lidocaine melting point, thereby creating a eutectic mixture with a high concentration of lidocaine in the oil phase. Based on bibliographic data, thymol creating a binary eutectic system containing lidocaine has been chosen. After addition of other excipients, an emulsion system was prepared and the drug was stabilized in the oil phase by a mixed nonionic emulsifier and carbomera. For the optimal anesthetic effects, the pH value should be adjusted; trometamol has been chosen as a suitable basic reacting excipient. Based on the addition of different amounts of trometamol, pH values of individual emulgels have been measured and the final composition of lidocaine emulgel has been created. A recipe for a 5 % lidocaine emulgel with the pH value of 9.1 has been created, based on the gel-forming substance carbomera with an emulsion of the oil phase containing a eutectic mixture of lidocaine and thymol, with an addition of ethanol and propylenglycol, stabilized by a mixed nonionic emulsifier. The advantage is the absence of other local anesthetics. PMID:23251958

  2. Colloidal carriers of isotretinoin for topical acne treatment: skin uptake, ATR-FTIR and in vitro cytotoxicity studies.

    PubMed

    Gürbüz, Aslı; Özhan, Gül; Güngör, Sevgi; Erdal, M Sedef

    2015-09-01

    Acne vulgaris is the chronical, multifactorial and complex disease of the pilosebaceous unit in the skin. The main goal of the topical therapy in acne is to target the drug to epidermal and deep dermal regions by minimizing systemic absorption . Isotretinoin, a retinoic acid derivative, is the most effective drug in acne pathogenesis. Because systemic treatment may cause many side effects, topical isotretinoin treatment is an option in the management of acne. However, due to its high lipophilic character, isotretinoin tends to accumulate in the upper stratum corneum, thus its penetration into the lower layers is limited, which restricts the efficiency of topical treatment. Microemulsions are fluid, isotropic, colloidal drug carriers that have been widely studied as drug delivery systems. The percutaneous transport of active agents can be enhanced by microemulsions when compared with their conventional formulations. The purpose of this study was to evaluate microemulsions as alternative topical carriers for isotretinoin with an objective to improve its skin uptake. After in vitro permeation studies, the dermal penetration of isotretinoin from microemulsions was investigated by tape stripping procedure. Confocal laser scanning microscopy provided insight about the localization of the drug in the skin. The interaction between the microemulsion components and stratum corneum lipids is studied by ATR-FTIR spectroscopy. The relative safety of the microemulsions was assessed in mouse embryonic fibroblasts using MTT viability test. The results indicate that microemulsion-based novel colloidal carriers have a potential for enhanced skin delivery and localization of isotretinoin.

  3. Jute batching oil: a tumor promoter on mouse skin

    SciTech Connect

    Mehrotra, N.K.; Kumar, S.; Agarwal, R.; Antony, M.

    1987-02-01

    A mineral oil essentially used in the jute industry for the batching of jute fibers, and earlier reported to be nontumorigenic on mouse skin, has been found to be a tumor promoter following a two-stage mouse-skin bioassay protocol. The types of tumors developed after initiation with a single dose of urethane or 3-methylcholanthrene (subcutaneously), followed by repeated skin painting with jute batching oil (JBO) included benign papillomas, keratoacanthomas, and fibrosarcomas. Chemical analysis of this oil indicated the total aromatic content was 11.71% and the amount of fluoranthene, pyrene, chrysene, and triphenylene was in the range of 192.54 to 227.79 mg/kg in the test sample. The underlying biochemical mechanism for the tumor-promoting effect of JBO seemed to operate through a different pathway rather than involving the induction of cytochrome-dependent monoxygenase and N-demethylase activities in the tissue.

  4. Jute batching oil: a tumor promoter on mouse skin.

    PubMed

    Mehrotra, N K; Kumar, S; Agarwal, R; Antony, M

    1987-02-01

    A mineral oil essentially used in the jute industry for the "batching" of jute fibers, and earlier reported to be nontumorigenic on mouse skin, has been found to be a tumor promoter following a two-stage mouse-skin bioassay protocol. The types of tumors developed after initiation with a single dose of urethane or 3-methylcholanthrene (subcutaneously), followed by repeated skin painting with jute batching oil (JBO) included benign papillomas, keratoacanthomas, and fibrosarcomas. Chemical analysis of this oil indicated the total aromatic content was 11.71% and the amount of fluoranthene, pyrene, chrysene, and triphenylene was in the range of 192.54 to 227.79 mg/kg in the test sample. The underlying biochemical mechanisms for the tumor-promoting effect of JBO seemed to operate through a different pathway rather than involving the induction of cytochrome-dependent monoxygenase and N-demethylase activities in the tissue.

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

    SciTech Connect

    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.

  6. Mechanical properties, skin permeation and in vivo evaluations of dexibuprofen-loaded emulsion gel for topical delivery.

    PubMed

    Jin, Sung Giu; Yousaf, Abid Mehmood; Son, Mi Woon; Jang, Sun Woo; Kim, Dong Wuk; Kim, Jong Oh; Yong, Chul Soon; Kim, Jeong Hoon; Choi, Han-Gon

    2015-02-01

    The aim of this research was to evaluate the gel properties, skin permeation and in vivo drug efficacy of a novel dexibuprofen-loaded emulsion gel for topical delivery. In this study, the dexibuprofen-loaded emulsion gel and ibuprofen-loaded emulsion gel were prepared with isopropanol, Tween 80, propylene glycol, isopropyl myristate and carbopol. Their mechanical properties such as hardness and adhesiveness were assessed. Moreover, their skin permeation, anti-inflammatory and anti-nociceptive efficacy were evaluated using Franz diffusion cell with the hairless mouse skin, the carrageenan-induced paw oedema test and paw pressure test in rat's hind paws compared with the commercial hydrogel, respectively. The dexibuprofen emulsion gel and ibuprofen emulsion gel provided significantly higher hardness and adhesiveness than the commercial hydrogel. The dexibuprofen emulsion gel enhanced skin permeability by about twofold and 3.5-fold without lag time compared to the ibuprofen emulsion gel and the commercial hydrogel, respectively, suggesting its faster skin permeation. Moreover, the anti-inflammatory efficacy and alleviation in carrageenan-induced inflammation was in the order of dexibuprofen emulsion gel > commercial hydrogel > ibuprofen emulsion gel. The dexibuprofen emulsion gel furnished significantly higher nociceptive thresholds than the ibuprofen emulsion gel and the commercial hydrogel, leading to the most improved anti-nociceptive efficacy. Thus, this dexibuprofen-loaded emulsion gel with good mechanical property, rapid skin permeation and excellent anti-inflammatory and anti-nociceptive efficacy would be a strong candidate for the topical delivery of anti-inflammatory dexibuprofen.

  7. Transgenic mouse model of malignant skin melanoma.

    PubMed Central

    Mintz, B; Silvers, W K

    1993-01-01

    Tyr-SV40E transgenic mice are specifically susceptible to melanoma due to expression of the oncogene in pigment cells. Mice of the more susceptible lines die young of early-onset eye melanomas, when skin melanomas are still infrequent and benign. To surmount this obstacle, skin from donors of two high-susceptibility lines was grafted to Tyr-SV40E hosts of a low-susceptibility line of the same inbred strain, thereby enabling the skin to outlive the donors and continue to grow in immunocompetent but tolerant hosts. Unexpectedly, donor pigment cells in all the grafts soon selectively proliferated close to areas of greatest wound healing, forming a dense black tracery, especially at the outer rim of the grafts. These lesions slowly grew radially within the grafts, producing irregular greyish patches. Local vertical thickenings then appeared and developed into small melanomas, which soon ulcerated through the epidermis. The tumors rapidly enlarged and became deeply invasive. Discrete black nevi also arose, with many becoming larger and distinctly blue, but those not near areas of pronounced wound healing did not progress to malignancy. In this first series, malignant melanoma resulted in all the grafts from the more susceptible of two donor lines and in some grafts from the other line. Distant metastases occurred in some cases from each line. Most tumors were hypomelanotic and heterogeneous, with lobes or areas differing in melanization. The results strongly suggest that growth factors and cytokines--known to be produced in wound repair--are triggering the growth and malignant conversion of these genetically susceptible melanocytes and that in the graft situation we are merely witnessing a caricature--a usefully exaggerated manifestation of the true events underlying the genesis of melanomas. The striking resemblance to the human malignancy, the genetic uniformity and different susceptibilities of the transgenic lines, and the experimental possibilities in the grafted

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

    PubMed

    Mishra, Sakshi; Tripathi, Anurag; Chaudhari, Bhushan P; Dwivedi, Premendra D; Pandey, Haushila P; Das, Mukul

    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 (84-672nmol/mouse) significantly enhanced dermal hyperplasia and skin edema. DON (336 and 672nmol) caused significant enhancement in [(3)H]-thymidine uptake in DNA along with increased myeloperoxidase and ornithine decarboxylase activities, suggesting tissue inflammation and cell proliferation. Furthermore, DON (168nmol) 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 168nmol) showed no tumorigenesis after 24weeks, 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 24weeks 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. PMID:24937323

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

    SciTech Connect

    Mishra, Sakshi; Tripathi, Anurag; Chaudhari, Bhushan P.; Dwivedi, Premendra D.; Pandey, Haushila P.; Das, Mukul

    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

  10. Oncogenic Radiation Abscopal Effects In Vivo: Interrogating Mouse Skin

    SciTech Connect

    Mancuso, Mariateresa; Leonardi, Simona; Giardullo, Paola; Pasquali, Emanuela; Tanori, Mirella; De Stefano, Ilaria; Casciati, Arianna; Naus, Christian C.; Pazzaglia, Simonetta; Saran, Anna

    2013-08-01

    Purpose: To investigate the tissue dependence in transmission of abscopal radiation signals and their oncogenic consequences in a radiosensitive mouse model and to explore the involvement of gap junction intercellular communication (GJIC) in mediating radiation tumorigenesis in off-target mouse skin. Methods and Materials: Patched1 heterozygous (Ptch1{sup +/−}) mice were irradiated at postnatal day 2 (P2) with 10 Gy of x-rays. Individual lead cylinders were used to protect the anterior two-thirds of the body, whereas the hindmost part was directly exposed to radiation. To test the role of GJICs and their major constituent connexin43 (Cx43), crosses between Ptch1{sup +/−} and Cx43{sup +/−} mice were similarly irradiated. These mouse groups were monitored for their lifetime, and skin basal cell carcinomas (BCCs) were counted and recorded. Early responses to DNA damage - Double Strand Breaks (DSBs) and apoptosis - were also evaluated in shielded and directly irradiated skin areas. Results: We report abscopal tumor induction in the shielded skin of Ptch1{sup +/−} mice after partial-body irradiation. Endpoints were induction of early nodular BCC-like tumors and macroscopic infiltrative BCCs. Abscopal tumorigenesis was significantly modulated by Cx43 status, namely, Cx43 reduction was associated with decreased levels of DNA damage and oncogenesis in out-of-field skin, suggesting a key role of GJIC in transmission of oncogenic radiation signals to unhit skin. Conclusions: Our results further characterize the nature of abscopal responses and the implications they have on pathologic processes in different tissues, including their possible underlying mechanistic bases.

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

    SciTech Connect

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

    2015-05-15

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

  12. Foot Pad Skin Biopsy in Mouse Models of Hereditary Neuropathy

    PubMed Central

    Dacci, Patrizia; Dina, Giorgia; Cerri, Federica; Previtali, Stefano Carlo; Lopez, Ignazio Diego; Lauria, Giuseppe; Feltri, Maria Laura; Bolino, Alessandra; Comi, Giancarlo; Wrabetz, Lawrence; Quattrini, Angelo

    2010-01-01

    Numerous transgenic and knockout mouse models of human hereditary neuropathies have become available over the past decade. We describe a simple, reproducible, and safe biopsy of mouse skin for histopathological evaluation of the peripheral nervous system (PNS) in models of hereditary neuropathies. We compared the diagnostic outcome between sciatic nerve and dermal nerves found in skin biopsy (SB) from the hind foot. A total of five animal models of different Charcot-Marie-Tooth neuropathies, and one model of congenital muscular dystrophy associated neuropathy were examined. In wild type mice, dermal nerve fibers were readily identified by immunohistochemistry, light, and electron microscopy and they appeared similar to myelinated fibers in sciatic nerve. In mutant mice, SB manifested myelin abnormalities similar to those observed in sciatic nerves, including hypomyelination, onion bulbs, myelin outfolding, redundant loops, and tomacula. In many strains, however, SB showed additional abnormalities—fiber loss, dense neurofilament packing with lower phosphorylation status, and axonal degeneration—undetected in sciatic nerve, possibly because SB samples distal nerves. SB, a reliable technique to investigate peripheral neuropathies in human beings, is also useful to investigate animal models of hereditary neuropathies. Our data indicate that SB may reveal distal axonal pathology in mouse models and permits sequential follow-up of the neuropathy in an individual mouse, thereby reducing the number of mice necessary to document pathology of the PNS. © 2010 Wiley-Liss, Inc. PMID:20878767

  13. Alterations in cell cycle regulation in mouse skin tumors.

    PubMed

    Balasubramanian, S; Ahmad, N; Jeedigunta, S; Mukhtar, H

    1998-02-24

    The connection between cell cycle and cancer has become obvious in as much as it is considered that dysregulated cellular proliferation is a hallmark of cancer. In many studies, the dysregulation of the cyclin-cdk-cki network has been reported in experimental animal and human tumors, but to our knowledge a complete profile of alterations in regulatory molecules in any tumor model system is lacking. In this study, we assessed the expression of various cyclins, cyclin dependent kinases, and cyclin kinase inhibitors in chemically induced squamous papillomas in SENCAR mouse skin. Western blot analysis data showed a significant upregulation of cyclins (31, 6, 19, and 12 folds elevation for cyclin-D1, D2, E, and A, respectively) in tumors compared to the normal skin. The protein expression of the cdk (1, 2, and 4) was also found to be elevated in tumors compared to normal skin (33 fold for cdk1, 14 fold for cdk2, and 9 fold for cdk4). In tumors, compared to the normal skin, a significant increase in the level of protein expression of p27 and p57 (4 and 3 fold, respectively) was evident. In normal skin, p16 and p21 were not detectable but significant expression of these proteins was detected in tumors. Taken together, these data provide evidence that cell cycle deregulation in G1-phase is a critical event during the course of two stage skin carcinogenesis. This may have relevance to epithelial cancers in general.

  14. Topical formulation containing hesperidin methyl chalcone inhibits skin oxidative stress and inflammation induced by ultraviolet B irradiation.

    PubMed

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

    2016-04-01

    Skin exposure to ultraviolet B (UVB) irradiation has increased significantly in recent years due to ozone depletion, and it represents the main cause of many skin diseases. Hesperidin methyl chalcone (HMC) is a compound used to treat vascular diseases that has demonstrated anti-inflammatory activities in pre-clinical studies. Herein, we tested the antioxidant activity of HMC in cell free systems and the in vivo effects of a stable topical formulation containing HMC in a mouse model of skin oxidative stress and inflammation induced by UVB irradiation. HMC presented ferric reducing power, neutralized 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and hydroxyl free radicals, and inhibited lipid peroxidation. In hairless mice, a topical formulation containing HMC inhibited UVB irradiation-induced skin edema, depletion of antioxidant capacity (ferric and ABTS reducing abilities and catalase activity), lipid peroxidation, superoxide anion production and mRNA expression of gp91phox (nicotinamide adenine dinucleotide phosphate [NADPH] oxidase 2 sub-unity). In addition, HMC inhibited UVB irradiation-induced depletion of reduced glutathione levels by maintaining glutathione peroxidase-1 and glutathione reductase mRNA expression, prevented down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression and increased heme oxygenase-1 mRNA expression. Finally, we demonstrated that topical application of the formulation containing HMC inhibited cytokine (TNF-α, IL-1β, IL-6, and IL-10) production induced by UVB irradiation. Therefore, this topical formulation containing HMC is a promising new therapeutic approach to protecting the skin from the deleterious effects of UVB irradiation. PMID:27021784

  15. In vivo gene silencing following non-invasive siRNA delivery into the skin using a novel topical formulation

    PubMed Central

    Hegde, Vikas; Hickerson, Robyn P.; Nainamalai, Sitheswaran; Campbell, Paul A.; Smith, Frances J.D.; McLean, W.H. Irwin; Leslie Pedrioli, Deena M.

    2014-01-01

    Therapeutics based on short interfering RNAs (siRNAs), which act by inhibiting the expression of target transcripts, represent a novel class of potent and highly specific next-generation treatments for human skin diseases. Unfortunately, the intrinsic barrier properties of the skin combined with the large size and negative charge of siRNAs make epidermal delivery of these macromolecules quite challenging. To help evaluate the in vivo activity of these therapeutics and refine delivery strategies we generated an innovative reporter mouse model that predominantly expresses firefly luciferase (luc2p) in the paw epidermis — the region of murine epidermis that most closely models the tissue architecture of human skin. Combining this animal model with state-of-the-art live animal imaging techniques, we have developed a real-time in vivo analysis work-flow that has allowed us to compare and contrast the efficacies of a wide range nucleic acid-based gene silencing reagents in the skin of live animals. While inhibition was achieved with all of the reagents tested, only the commercially available “self-delivery” modified Accell-siRNAs (Dharmacon) produced potent and sustained in vivo gene silencing. Together, these findings highlight just how informative reliable reporter mouse models can be when assessing novel therapeutics in vivo. Using this work-flow, we developed a novel clinically-relevant topical formulation that facilitates non-invasive epidermal delivery of unmodified and “self-delivery” siRNAs. Remarkably, a sustained > 40% luc2p inhibition was observed after two 1-hour treatments with Accell-siRNAs in our topical formulation. Importantly, our ability to successfully deliver siRNA molecules topically brings these novel RNAi-based therapeutics one-step closer to clinical use. PMID:25449884

  16. In vivo gene silencing following non-invasive siRNA delivery into the skin using a novel topical formulation.

    PubMed

    Hegde, Vikas; Hickerson, Robyn P; Nainamalai, Sitheswaran; Campbell, Paul A; Smith, Frances J D; McLean, W H Irwin; Pedrioli, Deena M Leslie

    2014-12-28

    Therapeutics based on short interfering RNAs (siRNAs), which act by inhibiting the expression of target transcripts, represent a novel class of potent and highly specific next-generation treatments for human skin diseases. Unfortunately, the intrinsic barrier properties of the skin combined with the large size and negative charge of siRNAs make epidermal delivery of these macromolecules quite challenging. To help evaluate the in vivo activity of these therapeutics and refine delivery strategies we generated an innovative reporter mouse model that predominantly expresses firefly luciferase (luc2p) in the paw epidermis--the region of murine epidermis that most closely models the tissue architecture of human skin. Combining this animal model with state-of-the-art live animal imaging techniques, we have developed a real-time in vivo analysis work-flow that has allowed us to compare and contrast the efficacies of a wide range nucleic acid-based gene silencing reagents in the skin of live animals. While inhibition was achieved with all of the reagents tested, only the commercially available "self-delivery" modified Accell-siRNAs (Dharmacon) produced potent and sustained in vivo gene silencing. Together, these findings highlight just how informative reliable reporter mouse models can be when assessing novel therapeutics in vivo. Using this work-flow, we developed a novel clinically-relevant topical formulation that facilitates non-invasive epidermal delivery of unmodified and "self-delivery" siRNAs. Remarkably, a sustained >40% luc2p inhibition was observed after two 1-hour treatments with Accell-siRNAs in our topical formulation. Importantly, our ability to successfully deliver siRNA molecules topically brings these novel RNAi-based therapeutics one-step closer to clinical use.

  17. Methods for Evaluating Topical Antibacterial Agents on Human Skin

    PubMed Central

    Marples, R. R.; Kligman, A. M.

    1974-01-01

    Three procedures were presented for appraising the ability of antibacterial chemicals and formulations to suppress the growth of microorganisms on human skin. In each of these, the microflora was quantified after the skin had been occlusively covered for a day or more, a circumstance which, in the absence of a deterrent, led to an explosive overgrowth by resident organisms. The data obtained related to (i) the capacity to prevent expansion of the normal microflora, (ii) the suppression of an already expanded flora, and (iii) the persistence of antibacterial effect 3 days after the last application. PMID:4840440

  18. DA 5505: a novel topical formulation of terbinafine that enhances skin penetration and retention.

    PubMed

    Thapa, Raj Kumar; Han, Sang-Duk; Park, Hyoung Geun; Son, Miwon; Jun, Joon Ho; Kim, Jong Oh

    2015-01-01

    Topical fungal infections can become severe if left untreated. Efficient treatment modalities for topical fungal infections aid the penetration of antifungal agents deep into viable skin layers. Terbinafine is a fungicidal agent that inhibits ergosterol, an essential fungal component. The main objective of this study was to evaluate skin permeation and retention of a terbinafine-loaded solution containing chitosan as a film former. Comparative assessment of skin permeation and retention was performed using a prepared formulation (DA 5505) and marketed formulations of terbinafine in murine and porcine skin. To mimic fungal infection of skin, keratinized skin was induced in NC/Nga mice. In comparison with the marketed formulations, DA 5505 exhibited significantly better skin permeation. The flux, permeation coefficient, and enhancement ratio of terbinafine were remarkably increased by DA 5505 in comparison with the marketed formulations, and lag time was dramatically reduced. DA 5505 significantly increased cumulative terbinafine retention in viable skin layers in comparison with the marketed solution, suggesting enhanced efficacy. Furthermore, DA 5505 exhibited superior skin permeation in normal skin and keratinized skin. Thus, the DA 5505 formulation has the potential to effectively deliver terbinafine to superficial and deep cutaneous fungal infections.

  19. Effects of a new topical combination on sensitive skin.

    PubMed

    Fauger, A; Lhoste, A; Chavagnac-Bonneville, M; Sayag, M; Jourdan, E; Ardiet, N; Perichaud, C; Trompezinski, S; Misery, L

    2015-01-01

    Using well-tolerated cosmetics or those with soothing effects is recommended to treat sensitive skin. However, we lack clinical studies. Two clinical trials were performed on sensitive skin in France and Thailand. The primary objective was to evaluate the preventive soothing effect. The secondary objectives were to evaluate the immediate soothing effect, product tolerance, and impact on quality of life. Evaluation methods included a stinging test and scoring erythema and stinging intensity. We also assessed tolerance, quality of life using the Dermatology Life Quality Index, and cosmetic qualities. The clinical trials were performed in France and Thailand to test efficacy in two different environments and on different ethnic skin. Interesting effects were observed in patients with sensitive skin in France and Thailand: a preventive soothing effect, a soothing effect on erythema, and an immediate soothing effect. In vivo biometrological, sodium lauryl sulfate, and capsaicin tests confirmed these data. A favorable effect on quality of life was also noted. The product was appreciated by volunteers for its efficacy, tolerance, and cosmetic qualities. A preliminary study on the effects on interleukin 8 was also included in the paper.

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

    PubMed

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

    2015-05-15

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

  1. Novel isotretinoin microemulsion-based gel for targeted topical therapy of acne: formulation consideration, skin retention and skin irritation studies

    NASA Astrophysics Data System (ADS)

    Patel, Mrunali R.; Patel, Rashmin B.; Parikh, Jolly R.; Patel, Bharat G.

    2016-04-01

    Isotretinoin was formulated in novel microemulsion-based gel formulation with the aim of improving its solubility, skin tolerability, therapeutic efficacy, skin-targeting efficiency and patient compliance. Microemulsion was formulated by the spontaneous microemulsification method using 8 % isopropyl myristate, 24 % Labrasol, 8 % plurol oleique and 60 % water as an external phase. All plain and isotretinoin-loaded microemulsions were clear and showed physicochemical parameters for the desired topical delivery and stability. The permeation profiles of isotretinoin through rat skin from selected microemulsion formulation followed zero-order kinetics. Microemulsion-based gel was prepared by incorporating Carbopol®971 in optimized microemulsion formulation having suitable skin permeation rate and skin uptake. Microemulsion-based gel showed desired physicochemical parameters and demonstrated advantage over marketed formulation in improving the skin tolerability of isotretinoin, indicating its potential in improving topical delivery of isotretinoin. The developed microemulsion-based gel may be a potential drug delivery vehicle for targeted topical delivery of isotretinoin in the treatment of acne.

  2. Moisturizing effect of topical cosmetic products applied to dry skin.

    PubMed

    Polaskova, Jana; Pavlackova, Jana; Vltavska, Pavlina; Mokrejs, Pavel; Janis, Rahula

    2013-01-01

    One of the complications of "diabetes mellitus" is termed diabetic foot syndrome, the first symptoms of which include changes in the skin's condition and properties. The skin becomes dehydrated, dry, and prone to excessive formation of the horny layer, its barrier function becoming weakened. This function can be restored by applying suitable cosmetic excipients containing active substances. The aim of this study was to evaluate and compare the effects of commercially available cosmetic products (CPs) designed for the care of diabetic foot, through a group of selected volunteers using noninvasive bioengineering methods. Statistical surveys (p < 0.05) evaluated these CPs as regards to their hydration effect and barrier properties. Special attention was devoted to CPs with the declared content of 10% urea, and that the influence of this preparation's ability to hydrate and maintain epidermal water in the epidermis was confirmed.

  3. Topical vitamin D analogue calcipotriol reduces skin fibrosis in experimental scleroderma.

    PubMed

    Usategui, Alicia; Criado, Gabriel; Del Rey, Manuel J; Faré, Regina; Pablos, José L

    2014-10-01

    Vitamin D analogues can reduce TGF-β pro-fibrotic signaling in dermal fibroblasts, but they may also induce a potentially pro-fibrotic thymic stromal lymphopoietin (TSLP)-dependent Th2 cytokine local response. We have analyzed the net effect of topical vitamin D analogue calcipotriol (CPT) on the cytokine profile and the development of fibrosis in experimental model of bleomycin-induced fibrosis. Mice were simultaneously treated with topical CPT or vehicle cream and skin fibrosis was measured by collagen deposition, Masson's trichrome staining and hydroxyproline content. Cytokine and TSLP gene expression was evaluated by quantitative RT-PCR. We showed that in bleomycin injected skin, CPT administration significantly enhanced TSLP and IL-13 gene expression, but did not modify the expression of other cytokines. Skin fibrosis and hydroxyproline content were significantly reduced in CPT compared to vehicle-treated mice. In normal skin, topical administration of CPT lacked a direct pro-fibrotic effect. Our results demonstrate that topical CPT superinduces the expression of the TSLP/IL-13 Th2 axis in fibrotic skin, but it has a net anti-fibrotic effect. These data support the therapeutic use of topical vitamin D analogues for skin fibrosis.

  4. Permeation of topically applied Magnesium ions through human skin is facilitated by hair follicles.

    PubMed

    Chandrasekaran, Navin Chandrakanth; Sanchez, Washington Y; Mohammed, Yousuf H; Grice, Jeffrey E; Roberts, Michael S; Barnard, Ross T

    2016-06-01

    Magnesium is an important micronutrient essential for various biological processes and its deficiency has been linked to several inflammatory disorders in humans. Topical magnesium delivery is one of the oldest forms of therapy for skin diseases, for example Dead Sea therapy and Epsom salt baths. Some anecdotal evidence and a few published reports have attributed amelioration of inflammatory skin conditions to the topical application of magnesium. On the other hand, transport of magnesium ions across the protective barrier of skin, the stratum corneum, is contentious. Our primary aim in this study was to estimate the extent of magnesium ion permeation through human skin and the role of hair follicles in facilitating the permeation. Upon topical application of magnesium solution, we found that magnesium penetrates through human stratum corneum and it depends on concentration and time of exposure. We also found that hair follicles make a significant contribution to magnesium penetration. PMID:27624531

  5. Dosimetry of PAH skin carcinogenesis: covalent binding of benzo(a)pyrene to mouse epidermal DNA

    SciTech Connect

    Shugart, L.; Holland, J.M.; Rahn, R.O.

    1983-01-01

    Benzo(a)pyrene (BaP) is metabolized to the chemically reactive anti and syn isomers of the 7,8-diol-9,10-epoxides of BaP (BPDE) which bind covalently to DNA to form DNA/BPDE complexes. Tetrols liberated from the DNA/BPDE complex by acid hydrolysis are easily quantified by h.p.l.c. using fluorescence detection. This approach allows femtomole amounts of BPDE associated with the DNA isolated from a single mouse to be detected using conventional instrumentation. The usefulness of this technique to estimate the interaction of BaP with DNA of mouse skin, both in the intact animal and in organ culture, was investigated. With mouse skin in organ culture it could be demonstrated that: (1) upon a single topical application of 5 ..mu..g of BaP, binding to DNA occurred via BPDE at a linear rate for up to 65 h, (2) the amount of binding was dose dependent at concentrations of BaP <10 ..mu..g.

  6. Topical distribution of acyclovir in normal equine skin and equine sarcoids: An in vitro study.

    PubMed

    Haspeslagh, M; Taevernier, L; Maes, A A; Vlaminck, L E M; De Spiegeleer, B; Croubels, S M; Martens, A M

    2016-06-01

    Topical acyclovir application is an owner-friendly treatment for occult equine sarcoids, without the caustic side-effects other topical treatments have. Variable clinical success rates have been described, but it is not known to what rate and extent acyclovir penetrates in and through equine skin from a topical formulation. In the current study, an in vitro Franz diffusion model was used to determine the permeation parameters for a generic 5% acyclovir cetomacrogol cream for both healthy and sarcoid equine skin. The distribution of acyclovir between different layers of both skin types was also evaluated. While acyclovir penetrated through both skin types, significantly less acyclovir permeated to the deep dermis of sarcoid skin (197.62ng/mm(3)) compared to normal skin (459.41ng/mm(3)). Within sarcoid skin samples, significantly higher acyclovir concentrations were found in the epidermis (983.59ng/mm(3)) compared to the superficial dermis (450.02ng/mm(3)) and the deep dermis. At each sample point, significantly more acyclovir permeated to the receptor fluid through normal skin compared to sarcoid skin, which is reflected in the significantly higher permeation parameters of normal skin. Normal skin was found to be more permissive for acyclovir, but even in sarcoid skin, enough acyclovir reached the deep dermis to treat a Herpes simplex virus infection. In the case of equine sarcoids, the treatment is aimed at the Bovine papillomavirus and no information is available on the susceptibility of the DNA polymerase of this virus for acyclovir. Therefore, further research is needed to determine the efficacy of acyclovir to treat equine sarcoids. PMID:27234546

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

    PubMed Central

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

    2014-01-01

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

  8. Inhibition of atopic dermatitis-like skin lesions by topical application of a novel ceramide derivative, K6PC-9p, in NC/Nga mice.

    PubMed

    Kang, Jong Soon; Yoon, Won Kee; Youm, Jong-Kyung; Jeong, Se Kyoo; Park, Byeong Deog; Han, Mi Hwa; Lee, Hyunju; Moon, Eun-Yi; Han, Sang-Bae; Lee, Chang Woo; Lee, Kiho; Park, Song-Kyu; Yang, Kyu-Hwan; Kim, Hwan Mook

    2008-11-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease that commonly begins in childhood. K6PC-9p (N-(Ethyl dihydrogenphosphate)-2-hexyl-3-oxo-decanamide) is a synthetic ceramide derivative of PC-9S (N-Ethanol-2-mirystyl-3-oxo-staramide), which was known to be effective in atopic patients. In this study, we examined the effect of topical application of K6PC-9p on skin inflammation and AD-like skin lesions in mouse models. K6PC-9p dose-dependently inhibited phorbol ester-induced increase in ear thickness in BALB/c mice. Moreover, topical application of K6PC-9p suppressed dust mite extract-induced AD-like skin lesions in NC/Nga mice. Histopathological analysis revealed that both ear swelling and leucocyte infiltration were suppressed by K6PC-9p treatment. K6PC-9p also suppressed IL-4 and TNF-alpha expression in the ears and mast cell infiltration into the ears in NC/Nga mice. Further study demonstrated that K6PC-9p inhibited ConA-induced IL-4 secretion and LPS-induced macrophage activation. Taken together, our results showed that topical application of K6PC-9p exerts beneficial effects in animal model of skin inflammation and AD, suggesting that K6PC-9p might be a promising topical agent for the treatment of inflammatory skin diseases.

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

    SciTech Connect

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

    2013-09-06

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

  10. Formulation study of topically applied O/W lotion containing vitamin D3 derivative, focusing on skin permeability of the drug.

    PubMed

    Harada, Shin-Ichi; Horisawa, Eijiro; Kano, Satoshi; Sugibayashi, Kenji

    2011-08-01

    Permeation of 22-oxacalcitriol-1α, 25-dihydroxyvitamin D(3) (OCT) through excited hairless mouse skin was determined after application of OCT as solutions and O/W lotions consisted of different polarities of solvents: medium-chain fatty acid triglyceride (MCT), myristate isopropyl (IPM), 1,3-butylene glycol (1,3-BG), and propylene glycol (PG). OCT concentration in skin was also followed after applying these formulations. A two-layer diffusion model was composed to analyze dermatopharmacokinetic profiles of OCT for each vehicle. In the OCT solutions, skin permeation profile of OCT differed depending on solvent polarity. The O/W lotion with a high MCT content led to a low amount of OCT in skin. On the other hand, the O/W lotion with a high 1,3-BG content led to a high amount of OCT in skin. This dermatopharmacokinetic analysis indicated that addition of MCT to the formulation decreases the skin/vehicle partition coefficient of OCT and increases the diffusion coefficient of OCT in skin. However, the opposite effects on these two parameters were found in the case of 1,3-BG. Thus, skin permeability of OCT differed depending on the solvents used in the formulation. These results indicate that skin permeability of OCT is influenced by the physicochemical properties (i.e. polarity) of OCT, solvent, and skin. Our findings on the solvent effects of the skin permeability of OCT are thus useful for designing topical drug formulation, especially in aiming for bioequivalent dosage formulas.

  11. Evaluation of seven sunscreens on hairless mouse skin

    SciTech Connect

    Walter, J.F.

    1981-01-01

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

  12. Topical methadone and meperidine analgesic synergy in the mouse

    PubMed Central

    Kolesnikov, Yuri A.; Oksman, Galina; Pasternak, Gavril W.

    2010-01-01

    Topical analgesics have many potential advantages over systemic administration. Prior work has shown potent analgesic activity of a number of topical opioids in the radiant heat tailflick assay. The current study confirms the analgesic activity of morphine and extends it to two other mu opioids, methadone and meperidine. Combinations of topical morphine and lidocaine are synergistic. Similarly, the combination of methadone and lidocaine is synergistic. While there appeared to be some potentiation with the combination of meperidine and lidocaine, it did not achieve significance. Systemically, prior studies have shown that co-administration of morphine and methadone was synergistic. The combination of morphine and methadone was also synergistic when given topically. In contrast, the combination of morphine and meperidine was not synergistic systemically and it was not synergistic topically. Thus, the pharmacology of topical opioids mimics that seen with systemic administration. Their activity in the topical model supports their potential utility while the local limitation of their actions offers the possibility of a reduced side-effect profile. PMID:20433826

  13. Estimation of skin concentrations of topically applied lidocaine at each depth profile.

    PubMed

    Oshizaka, Takeshi; Kikuchi, Keisuke; Kadhum, Wesam R; Todo, Hiroaki; Hatanaka, Tomomi; Wierzba, Konstanty; Sugibayashi, Kenji

    2014-11-20

    Skin concentrations of topically administered compounds need to be considered in order to evaluate their efficacies and toxicities. This study investigated the relationship between the skin permeation and concentrations of compounds, and also predicted the skin concentrations of these compounds using their permeation parameters. Full-thickness skin or stripped skin from pig ears was set on a vertical-type diffusion cell, and lidocaine (LID) solution was applied to the stratum corneum (SC) in order to determine in vitro skin permeability. Permeation parameters were obtained based on Fick's second law of diffusion. LID concentrations at each depth of the SC were measured using tape-stripping. Concentration-depth profiles were obtained from viable epidermis and dermis (VED) by analyzing horizontal sections. The corresponding skin concentration at each depth was calculated based on Fick's law using permeation parameters and then compared with the observed value. The steady state LID concentrations decreased linearly as the site became deeper in SC or VED. The calculated concentration-depth profiles of the SC and VED were almost identical to the observed profiles. The compound concentration at each depth could be easily predicted in the skin using diffusion equations and skin permeation data. Thus, this method was considered to be useful for promoting the efficient preparation of topically applied drugs and cosmetics.

  14. Topical tocopherol acetate reduces post-UVB, sunburn-associated erythema, edema, and skin sensitivity in hairless mice.

    PubMed

    Trevithick, J R; Xiong, H; Lee, S; Shum, D T; Sanford, S E; Karlik, S J; Norley, C; Dilworth, G R

    1992-08-01

    Exposure of the skin of the back of skh-1 hairless mice to UVB (310 nm peak) irradiation at doses of 0.115-0.23 J/cm2 results after 24-48 h in an erythema which can be quantified using an erythema meter, providing a useful model of sunburn. Application of pure d-alpha-tocopherol acetate, a thick oil, to the skin immediately following the exposure to UVB significantly reduces the increase in erythema index, by 40-55%. At the lower dose (0.115 J/cm2), skin thickness (associated with edematous swelling of the sunburned skin) was measured by a novel non-invasive technique not previously reported for this purpose--magnetic resonance imaging (MRI). In two experiments the UVB-induced increase in skin thickness was significantly reduced at 24 hr by 29 and 54%, and at 48 hr by 26 and 61%. After 8 days the untreated irradiated mouse skin still showed a significant increase in thickness (24%) compared to the untreated unirradiated control, while the treated irradiated control was not significantly thicker than the unexposed control. Skin sensitivity was tested using a modification of the technique of esthesiometry, by observing rapid avoidance responses of the mouse to a pressure of 0.96 g/cm2 exerted by applying to the skin the tip of a nylon esthesiometer fiber extended to 60 mm in length. The untreated irradiated mice were more sensitive (p less than 0.07, Wilcoxon test) than the treated irradiated mice, and also significantly different from the untreated unirradiated control mice (p less than 0.04, Wilcoxon test), but the treated irradiated mice were not significantly differently sensitive when compared to the unirradiated controls (p less than 0.32). Taken together these data indicate that the erythema, edema, and skin sensitivity commonly associated with UVB-induced sunburn are significantly reduced by topical application of tocopherol acetate even after the exposure has occurred. This observation suggests that treatment of sunburn may be possible even after the

  15. Dorsal skin reactions of hairless dogs to topical treatment with corticosteroids.

    PubMed

    Kimura, T; Doi, K

    1999-01-01

    Dorsal skin reactions to continuous topical treatment with different types of corticosteroids were histologically investigated in hairless descendants of Mexican hairless dogs. The preparations tested were prednisolone (ST-1; weak), fluocinolone acetonide (ST-2; moderate), diflucortolone valrerate (ST-3; strong), and mometasone furoate (ST-4; very strong). Grossly, the sites treated with ST-3 and ST-4 showed moderate inflammatory reactions. After completion of the corticosteroid treatment, both sites were less pigmented and had a thin texture. The severity of histologic changes in the skin was dependent on the efficacy of the corticosteroids. The epidermis was prominently thinned from 1 wk after treatment with the corticosteroids, resulting in a flat dermis-epidermis junction. By the end of the corticosteroid treatment, these lesions became progressively more severe. At 2 wk after completion of topical treatment, the epidermal thickness in the sites treated with ST-1 and ST-2 began to return to normal values, whereas the epidermis of the skin treated with ST-3 and ST-4 became thinner. At 3-4 wk after topical treatment with ST-3 and ST-4, the dermis showed hyalinization of collagen bundles. These dermatologic findings in hairless dogs are in accordance with steroid-induced skin atrophy of human beings. These results suggest that the skin of hairless dogs responds sensitively to topical corticosteroids and that these animals are a useful model for investigating the efficacy and adverse effects of cutaneous topical corticosteroids. PMID:10528632

  16. Prolonged treatment of fair-skinned mice with topical forskolin causes persistent tanning and UV protection.

    PubMed

    Spry, Malinda L; Vanover, Jillian C; Scott, Timothy; Abona-Ama, Osama; Wakamatsu, Kazumasa; Ito, Shosuke; D'Orazio, John A

    2009-04-01

    We previously reported that topical application of forskolin to the skin of fair-skinned MC1R-defective mice with epidermal melanocytes resulted in accumulation of eumelanin in the epidermis and was highly protective against UV-mediated cutaneous injury. In this report, we describe the long-term effects of chronic topical forskolin treatment in this animal model. Forskolin-induced eumelanin production persisted through 3 months of daily applications, and forskolin-induced eumelanin remained protective against UV damage as assessed by minimal erythematous dose (MED). No obvious toxic changes were noted in the skin or overall health of animals exposed to prolonged forskolin therapy. Body weights were maintained throughout the course of topical forskolin application. Topical application of forskolin was associated with an increase in the number of melanocytes in the epidermis and thickening of the epidermis due, at least in part, to an accumulation of nucleated keratinocytes. Together, these data suggest in this animal model, short-term topical regular application of forskolin promotes eumelanin induction and that over time, topical forskolin treatment is associated with persistent melanization, epidermal cell accumulation, and skin thickening.

  17. Radiation effect in mouse skin: Dose fractionation and wound healing

    SciTech Connect

    Gorodetsky, R.; Mou, X.D.; Fisher, D.R.; Taylor, J.M.; Withers, H.R. )

    1990-05-01

    Radiation induced dermal injury was measured by the gain in the physical strength of healing wounds in mouse skin. A sigmoid dose response for the inhibition of wound healing 14 days after surgery was found for single doses of X rays. The sparing of dermal damage from fractionation of the X-ray dose was quantified in terms of the alpha/beta ratio in the linear-quadratic (LQ) model, at a wide range of doses per fraction reaching as low as about 1 Gy. The fit and the appropriateness of the LQ model for the skin wound healing assay was examined with the use of the Fe-plot in which inverse total dose is plotted versus dose per fraction for wound strength isoeffects. The alpha/beta ratio of the skin was about 2.5 Gy (95% confidence of less than +/- 1 Gy) and was appropriate over a dose range of 1 Gy to about 8 Gy. The low alpha/beta value is typical for a late responding tissue. This assay, therefore, has the advantage of measuring and forecasting late radiation responses of the dermis within a short time after irradiation.

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

    SciTech Connect

    Abel, E.L.; Boulware, S.; Fields, T.; McIvor, E.; Powell, K.L.; DiGiovanni, J.; Vasquez, K.M.; MacLeod, M.C.

    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.

  19. Topical application of a novel ceramide derivative, K6PC-9, inhibits dust mite extract-induced atopic dermatitis-like skin lesions in NC/Nga mice.

    PubMed

    Kang, Jong Soon; Youm, Jong-Kyung; Jeong, Se Kyoo; Park, Byeong Deog; Yoon, Won Kee; Han, Mi Hwa; Lee, Hyunju; Han, Sang-Bae; Lee, Kiho; Park, Song-Kyu; Lee, Seung Hun; Yang, Kyu-Hwan; Moon, Eun-Yi; Kim, Hwan Mook

    2007-12-15

    Atopic dermatitis (AD) is a chronic inflammatory skin disease. K6PC-9 (N-Ethanol-2-hexyl-3-oxo-decanamide) is a novel synthetic ceramide derivative of PC-9S (N-Ethanol-2-mirystyl-3-oxo-stearamide), which was known to be effective in atopic and psoriatic patients. To investigate the immunomodulatory activity of K6PC-9, we examined the effect of K6PC-9 on T lymphocyte and macrophage function and the effect of topical application of K6PC-9 on skin inflammation and AD-like skin lesions in mouse models. K6PC-9 had no effect on concanavalin A-induced proliferation, interleukin (IL)-2 secretion and IL-4 secretion in mouse splenocytes. In contrast, lipopolysaccharide-induced nitrite generation was potently suppressed by K6PC-9 in mouse peritoneal macrophages. In mouse model of skin inflammation, K6PC-9 inhibited phorbol ester-induced increase in ear thickness and expression of tumor necrosis factor-alpha in the ear of BALB/c mice. Topical application of K6PC-9 also suppressed mite extract-induced AD-like skin lesions in NC/Nga mice. Increase in ear thickness was significantly inhibited by K6PC-9 in this model. K6PC-9 also blocked the infiltration of mast cells and neutrophils into the ear. Further study demonstrated that the mRNA expression of tumor necrosis factor-alpha and adhesion molecules, such as vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin, was also suppressed by K6PC-9 in the ear of mite extract-treated NC/Nga mice. Taken together, the results presented in this report show that K6PC-9 has an anti-inflammatory potential and exerts beneficial effects in an animal model of AD, indicating that K6PC-9 might be used as a topical agent for the treatment of AD.

  20. Phase IIB Randomized Study of Topical Difluoromethylornithine and Topical Diclofenac on Sun-Damaged Skin of the Forearm.

    PubMed

    Jeter, Joanne M; Curiel-Lewandrowski, Clara; Stratton, Steven P; Myrdal, Paul B; Warneke, James A; Einspahr, Janine G; Bartels, Hubert G; Yozwiak, Michael; Bermudez, Yira; Hu, Chengcheng; Bartels, Peter; Alberts, David S

    2016-02-01

    Prevention of nonmelanoma skin cancers remains a health priority due to high costs associated with this disease. Diclofenac and difluoromethylornithine (DFMO) have demonstrated chemopreventive efficacy for cutaneous squamous cell carcinomas. We designed a randomized study of the combination of DFMO and diclofenac in the treatment of sun-damaged skin. Individuals with visible cutaneous sun damage were eligible. Subjects were randomized to one of the three groups: topical DFMO applied twice daily, topical diclofenac applied daily, or DFMO plus diclofenac. The treatment was limited to an area on the left forearm, and the duration of use was 90 days. We hypothesized that combination therapy would have increased efficacy compared with single-agent therapy. The primary outcome was change in karyometric average nuclear abnormality (ANA) in the treated skin. Individuals assessing the biomarkers were blinded regarding the treatment for each subject. A total of 156 subjects were randomized; 144 had baseline and end-of-study biopsies, and 136 subjects completed the study. The ANA unexpectedly increased for all groups, with higher values correlating with clinical cutaneous inflammation. Nearly all of the adverse events were local cutaneous effects. One subject had cutaneous toxicity that required treatment discontinuation. Significantly more adverse events were seen in the groups taking diclofenac. Overall, the study indicated that the addition of topical DFMO to topical diclofenac did not enhance its activity. Both agents caused inflammation on a cellular and clinical level, which may have confounded the measurement of chemopreventive effects. More significant effects may be observed in subjects with greater baseline cutaneous damage.

  1. In vivo formation and persistence of DNA and protein adducts in mouse and rat skin exposed to (+/-)benzo(a)pyrene-4,5-oxide

    SciTech Connect

    Rojas, M.; Alexandrov, K.

    1986-02-01

    The objective of the present study was to compare DNA and protein adduct formation of benzo(a)pyrene-4,5-oxide (BPO) in vivo and to determine the persistence of the adducts in both mouse and rat epidermis. (+/-)BPO at a dose of 100 nmol/mouse and 200 nmol/rat was topically applied to male Swiss mice and Wistar rats. Three hours after application, there was 3-fold less binding of BPO to mouse epidermal DNA than to rat epidermal DNA; inversely, the amount of BPO bound to mouse skin protein was 3.6 times higher than in rat skin protein. One and three weeks after application of BPO, persistence of 17-20% of the initial amount of BPO-DNA adducts and 2-4% of initial amount of BPO bound to protein was detected in both mouse and rat skin epidermis. H.p.l.c. analysis of the enzymatic hydrolysates of DNA from mouse and rat epidermis 3 h after application of BPO showed five distinct products: one early-eluting, two BPO-deoxyguanosine (dGuo) (ratio 1.5:1) and two BPO-deoxyadenosine (dAdo) adducts (ratio 2:1). The ratio of the total modified dGuo to the total modified dAdo was 2:1. The amount of total BPO-dGuo and BPO-dAdo adducts was 3.5 times greater in rat than in mouse epidermis. Persistence of the major BPO-dAdo adduct was observed in mouse and rat epidermal DNA, and 1 and 3 weeks after topical application of BPO there was a 6-fold greater amount of the persisting BPO-dAdo adduct in rat skin epidermis than in mouse skin epidermis (4.1 and 0.66 pmol/mg DNA, respectively). Minor amounts of the BPO-dGuo were found to persist in rat skin epidermis DNA.

  2. The skin health and beauty pyramid: a clinically based guide to selecting topical skincare products.

    PubMed

    Mayoral, Flor A; Kenner, Julie R; Draelos, Zoe Diana

    2014-04-01

    The use of cosmeceuticals by patients is now commonplace. Without consultation and direction from an informed clinician, marketing pressures can lead consumers to make poor product choices that can result in wasted money and unsatisfactory outcomes. Skin professionals need a scientifically based, succinct tool to guide their patients toward best topical skincare practices. The Skin Health and Beauty Pyramid is an educational framework and product guide created from extensive scientific literature and study review on ingredients, formulations and technologies affecting skin biology. This clinical tool can simplify product choices for physicians and clinicians in the process of professionally guiding patients toward the optimal use of topical products to achieve best outcomes for skin health and beauty. PMID:24719060

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

    PubMed Central

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

    2016-01-01

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

  4. Topical steroid therapy induces pro-tolerogenic changes in Langerhans cells in human skin.

    PubMed

    Ali, Mohammad Alhadj; Thrower, Sally L; Hanna, Stephanie J; Coulman, Sion A; Birchall, James C; Wong, F Susan; Dayan, Colin Mark; Tatovic, Danijela

    2015-11-01

    We have investigated the efficacy of conditioning skin Langerhans cells (LCs) with agents to promote tolerance and reduce inflammation, with the goal of improving the outcomes of antigen-specific immunotherapy. Topical treatments were assessed ex vivo, using excised human breast skin maintained in organ bath cultures, and in vivo in healthy volunteers by analysing skin biopsies and epidermal blister roof samples. Following topical treatment with a corticosteroid, tumour necrosis factor-α levels were reduced in skin biopsy studies and blister fluid samples. Blister fluid concentrations of monocyte chemoattractant protein-1, macrophage inflammatory proteins -1α and 1β and interferon-γ inducible protein-10 were also reduced, while preserving levels of interleukin-1α (IL-1α), IL-6, IL-8 and IL-10. Steroid pre-treatment of the skin reduced the ability of LCs to induce proliferation, while supernatants showed an increase in the IL-10/interferon-γ ratio. Phenotypic changes following topical steroid treatment were also observed, including reduced expression of CD83 and CD86 in blister-derived LCs, but preservation of the tolerogenic signalling molecules immunoglobulin-like transcript 3 and programmed death-1. Reduced expression of HLA-DR, CD80 and CD86 were also apparent in LCs derived from excised human skin. Topical therapy with a vitamin D analogue (calcipotriol) and steroid, calcipotriol alone or vitamin A elicited no significant changes in the parameters studied. These experiments suggest that pre-conditioning the skin with topical corticosteroid can modulate LCs by blunting their pro-inflammatory signals and potentially enhancing tolerance. We suggest that such modulation before antigen-specific immunotherapy might provide an inexpensive and safe adjunct to current approaches to treat autoimmune diseases.

  5. Evaluation of topically applied copper(II) oxide nanoparticle cytotoxicity in human skin organ culture.

    PubMed

    Cohen, Dror; Soroka, Yoram; Ma'or, Zeev; Oron, Miriam; Portugal-Cohen, Meital; Brégégère, François Menahem; Berhanu, Deborah; Valsami-Jones, Eugenia; Hai, Noam; Milner, Yoram

    2013-02-01

    The increasing use of nano-sized materials in our environment, and in many consumer products, dictates new safety concerns. In particular, adequate experimental models are needed to evaluate skin toxicity of metal oxide ions, commonly found in cosmetic and dermatologic preparations. We have addressed the biological effects of topically applied copper oxide (CuO) nanoparticles in human skin organ cultures, using light and electron microscopy, and biochemical tests. Nanoparticles were more toxic than micro-sized particles, and their effects were stronger when supplied in growth medium than in topical application. Still topically applied CuO nanoparticles induced inflammatory cytokine secretion and necrosis, especially in epidermis deprived of its protective cornea. Since nanoparticle penetration was not seen, we propose that they may adhere to skin surface, react with the local acidic environment, and generate soluble ions that make their way to inner sites. This work illustrates the abilities of skin organ culture to evaluate the biological effects of topically-applied materials on skin in vitro. PMID:22954531

  6. Phase 1 study of topical perillyl alcohol cream for chemoprevention of skin cancer.

    PubMed

    Stratton, Steven P; Saboda, Kathy Lynn; Myrdal, Paul B; Gupta, Abhishek; McKenzie, Naja E; Brooks, Chris; Salasche, Stuart J; Warneke, James A; Ranger-Moore, James; Bozzo, Paul D; Blanchard, James; Einspahr, Janine G; Dorr, Robert T; Levine, Norman; Alberts, David S

    2008-01-01

    Perillyl alcohol (POH) is a natural product derived from plants such as cherry and lavendin. Previous studies have indicated that topical POH inhibits ultraviolet (UV) B-induced skin carcinogenesis in vivo, and it may be an effective chemopreventive agent for skin cancer. We performed a 1-mo, first-in-man, Phase 1 trial of topically administered POH cream in human subjects. Endpoints included safety and evaluation of any histopathological changes in skin after 1 mo use of POH cream. We randomized 25 subjects with normal, healthy skin with little or no sun damage and no history of skin cancer in a double-blind fashion to receive topical POH (0.76% wt/wt) on 1 forearm with placebo cream applied to the other forearm twice daily for 30 days. Subjects were monitored for toxicity, and a 4 mm punch biopsy in the treated area was performed at the end of study for histopathological evaluation. The topical cream was well tolerated. No serious cutaneous toxicities, systemic toxicities, or histopathological abnormalities were observed. A total of 8 subjects (32%) reported mild adverse events possibly or probably related to use of cream including reversible appearance of 1 to 2 small papules. However, there was no significant difference between lesions appearing on the POH treated forearm vs. the placebo-treated forearm. PMID:18444166

  7. Preventive effect of antihistaminics on mouse skin photosensitization with hematoporphyrin derivative

    NASA Astrophysics Data System (ADS)

    Fu, Nai-wu; Yan, Li-xue

    1993-03-01

    Beta-carotene 100 mg/kg per day or vitamin C 50 mg/kg per day was administered orally for two days and did not prevent mouse skin photosensitization caused by hematoporphyrin derivative (HpD). However, (beta) -carotene 100 mg/kg per day administered intramuscularly for two days prevented mouse skin reaction. Cimetidine and benadryl 10 mg/kg per day, P.O.X 2, effectively prevented mouse skin reaction. This suggests histamine may be involved in skin photoreaction induced by HpD.

  8. Penetration of oligonucleotides into mouse organism through mucosa and skin.

    PubMed

    Vlassov, V V; Karamyshev, V N; Yakubov, L A

    1993-08-01

    Benzylamide 5'-32P-oligonucleotide derivatives were shown to penetrate into mice organism when administered by various routes; intranasally, per os, intravaginally and per rectum. In all cases, the compounds are rapidly accumulated in blood and guts. Analysis of the radioactive material from blood and pancreas revealed intact oligonucleotides. Although concentrations of oligonucleotides in tissues differ considerably by the various methods of administration, the efficiency of delivery is sufficient to consider all the routes as being of therapeutic value. Dose effect on the efficiency of oligonucleotide penetration into mice suggests the transport to be a saturable process. Application of an oligonucleotide lotion on mice ear helices results in reproducible accumulation of radioactivity in the animal tissues. Effectiveness of oligonucleotide delivery into mouse through skin can be improved by using electrophoretic procedure.

  9. Strengthening the Skin with Topical Delivery of Keratinocyte Growth Factor-1 Using a Novel DNA Plasmid

    PubMed Central

    Dou, Chunqing; Lay, Frank; Ansari, Amir Mehdi; Rees, Donald J; Ahmed, Ali Karim; Kovbasnjuk, Olga; Matsangos, Aerielle E.; Du, Junkai; Hosseini, Sayed Mohammad; Steenbergen, Charles; Fox-Talbot, Karen; Tabor, Aaron T.; Williams, James A; Liu, Lixin; Marti, Guy P; Harmon, John W

    2014-01-01

    Fragile skin, susceptible to decubitus ulcers and incidental trauma, is a problem particularly for the elderly and for those with spinal cord injury. Here, we present a simple approach to strengthen the skin by the topical delivery of keratinocyte growth factor-1 (KGF-1) DNA. In initial feasibility studies with the novel minimalized, antibiotic-free DNA expression vector, NTC8385-VA1, the reporter genes luciferase and enhanced green fluorescent protein were delivered. Transfection was documented when luciferase expression significantly increased after transfection. Microscopic imaging of enhanced green fluorescent protein–transfected skin showed green fluorescence in hair follicles, hair shafts, and dermal and superficial epithelial cells. With KGF-1 transfection, KGF-1 mRNA level and protein production were documented with quantitative reverse transcriptase–polymerase chain reaction and immunohistochemistry, respectively. Epithelial thickness of the transfected skin in the KGF group was significantly increased compared with the control vector group (26 ± 2 versus 16 ± 4 µm) at 48 hours (P = 0.045). Dermal thickness tended to be increased in the KGF group (255 ± 36 versus 162 ± 16 µm) at 120 hours (P = 0.057). Biomechanical assessment showed that the KGF-1–treated skin was significantly stronger than control vector–transfected skin. These findings indicate that topically delivered KGF-1 DNA plasmid can increase epithelial thickness and strength, demonstrating the potential of this approach to restore compromised skin. PMID:24434934

  10. Conflicting effects of DMSO on mouse skin tumorigenesis

    SciTech Connect

    Jacoby, W.T.; Weiss, H.S.

    1986-03-05

    A number of solvents, including dimethylsulfoxide (DMSO), when substituted for acetone as the vehicle for the potent promoter phorbol-12-myristate-13-acetate (PMA) in the two-stage mouse skin cancer model, tend to inhibit tumorigenesis. DMSO was investigated further because the literature is ambiguous concerning its effect in both single and multi-stage carcinogenesis. As solvent for the complete carcinogen benzo(a)pyrene (BaP, 125 mg in 40 ..mu..l 2x/wk), tumor yield increased an avg of 245% (3 trials in C3H mice) compared to acetone/BaP. However, in the two-stage model (CD-1 mice initiated with 50-100 ..mu..g DMBA) DMSO as the vehicle for PMA (5 ..mu..g in 40 ..mu..l 2x/wk) reduced tumor yield to 34% of the PMA/acetone controls. To test whether the inhibition was an in vitro effect, 40 ..mu..l DMSO was applied at the initiation site, the back, up to one hr before PMA/acetone. In three trials tumor yield averaged 23% of controls. To determine whether the DMSO effect was directly on initiated cells or indirectly via the systemic circulation, 40 ..mu..l DMSO was applied prior to promotion at a site distant from initiation/promotion, the abdomen. In three trials, DMSO enhanced tumor yield by 194%. DMSO itself had no initiating or promotion effects. Thus, it appears that DMSO may either inhibit or enhance mouse skin tumorigenesis depending on its method of application.

  11. Coumarin derivatives, but not coumarin itself, cause skin irritation via topical delivery.

    PubMed

    Pan, Tai-Long; Wang, Pei-Wen; Aljuffali, Ibrahim A; Leu, Yann-Lii; Hung, Yi-Yun; Fang, Jia-You

    2014-04-21

    Coumarin and its derivatives are widely employed as a fragrance in cosmetics and skin care products. The skin absorption level and possible disruption to the skin by topical application of coumarins were evaluated in this study. Percutaneous absorption of osthole, daphnoretin, coumarin, byakangelicin, and 7-hydroxycoumarin was assessed in vitro and in vivo. Skin physiology measurements and immunoblotting were utilized as methodologies for validating toxicity. The relationship between structures and permeation/toxicity of coumarins was elucidated. Both equimolar concentration and saturated solubility in 30% ethanol were used as the applied dose. Osthole with the most lipophilic characteristic demonstrated the greatest skin accumulation, followed by coumarin and 7-hydroxycoumarin. Coumarin was the permeant with the highest flux across the skin. The trend of in vivo deposition was consistent with that of the in vitro profiles. Skin uptake of osthole was 8-fold higher than that of coumarin. Hair follicles played a significant role as a pathway for transport of coumarin according to the examination of follicular accumulation. Osthole and 7-hydroxycoumarin slightly, but significantly, enhanced transepidermal water loss after a consecutive 5-day administration. The immunoblotting profiling verified the role of proliferation in skin damage induced by osthole, byakangelicin, and 7-hydroxycoumarin. The proliferation-related proteins examined in this work included glucose-regulated proteins, cytokeratin, and C-myc. Daphnoretin and coumarin showed a negligible alteration on protein biomarkers. The experimental results suggested that skin irritation caused by coumarins was mainly derived from the analogs but not from coumarin itself.

  12. TOPICAL APPLICATION OF LAMININ-322 TO DIABETIC MOUSE WOUNDS

    PubMed Central

    Sullivan, Stephen R.; Underwood, Robert A.; Sigle, Randall O.; Fukano, Yuko; Muffley, Lara A.; Usui, Marcia L.; Gibran, Nicole S.; Antezana, Marcos A.; Carter, William G.; Olerud, John E.

    2007-01-01

    Background Keratinocyte migration is essential for wound healing and diabetic wound keratinocytes migrate poorly. Keratinocyte migration and anchorage appears to be mediated by laminin-332 (LM-332). Impaired diabetic wound healing may be due to defective LM-332 mediated keratinocyte migration. Objective To evaluate LM-332 expression in diabetic (db/db) and control (db/-) mice and to test LM-332 wound healing effects when applied to mouse wounds. Methods LM-332 expression in mouse wounds was evaluated using immunohistochemistry. LM-332 wound healing effects were evaluated by directly applying soluble LM-332, a LM-332 biomaterial, or a control to mouse wounds. Percent wound closure and histology score, based on healing extent, were measured. Results Precursor LM-332 expression was markedly reduced in db/db when compared to db/- mice. In vitro, soluble LM-332 and LM-332 biomaterial demonstrated significant keratinocyte adhesion. In vivo, soluble LM-332 treated wounds had the highest histology score, but significant differences were not found between wound treatments (p>0.05). No differences in percentage wound closure between treatment and control wounds were found (p>0.05). Conclusion The db/db wounds express less precursor LM-332 when compared to db/-. However, LM-332 application did not improve db/db wound healing. LM-332 purified from keratinocytes was primarily physiologically cleaved LM-332 and may not regulate keratinocyte migration. Application of precursor LM-332 rather than cleaved LM-332 may be necessary to improve wound healing, but this isoform is not currently available in quantities sufficient for testing. PMID:17719208

  13. Identification of glycoproteins from mouse skin tumors and plasma

    PubMed Central

    Tian, Yuan; Kelly-Spratt, Karen S.; Kemp, Christopher J.; Zhang, Hui

    2010-01-01

    Plasma has been the focus of testing different proteomic technologies for the identification of biomarkers due to its ready accessibility. However, it is not clear if direct proteomic analysis of plasma can be used to discover new marker proteins from tumor that are associated with tumor progression. Here, we reported that such proteins can be detected in plasma in a chemical induced skin cancer mouse model. We analyzed glycoproteins from both benign papillomas and malignant carcinomas from mice using our recently developed platform, solid-phase extraction of glycopeptides (SPEG) and mass spectrometry, and identified 463 unique N-linked glycosites from 318 unique glycoproteins. These include most known extracellular proteins that have been reported to play roles in skin cancer development such as thrombospondin, cathepsins, epidermal growth factor receptor, cell adhesion molecules, cadherins, integrins, tuberin, fibulin, TGFβ receptor, etc. We further investigated whether these tumor proteins could be detected in plasma from tumor bearing mice using isotope labeling and 2D-LC-MALDI-MS/MS. Two tumor glycoproteins, Tenascin-C and Arylsulfatase B, were identified and quantified successfully in plasma from tumor bearing mice. This result indicates that analysis of tumor associated proteins in tumors and plasma by method using glycopeptide capture, isotopic labeling, and mass spectrometry can be used as a discovery tool to identify candidate tumor proteins that may be detected in plasma. PMID:21072318

  14. Safety evaluation of topical applications of ethanol on the skin and inside the oral cavity

    PubMed Central

    Lachenmeier, Dirk W

    2008-01-01

    Ethanol is widely used in all kinds of products with direct exposure to the human skin (e.g. medicinal products like hand disinfectants in occupational settings, cosmetics like hairsprays or mouthwashes, pharmaceutical preparations, and many household products). Contradictory evidence about the safety of such topical applications of the alcohol can be found in the scientific literature, yet an up-to-date risk assessment of ethanol application on the skin and inside the oral cavity is currently lacking. The first and foremost concerns of topical ethanol applications for public health are its carcinogenic effects, as there is unambiguous evidence for the carcinogenicity of ethanol orally consumed in the form of alcoholic beverages. So far there is a lack of evidence to associate topical ethanol use with an increased risk of skin cancer. Limited and conflicting epidemiological evidence is available on the link between the use of ethanol in the oral cavity in the form of mouthwashes or mouthrinses and oral cancer. Some studies pointed to an increased risk of oral cancer due to locally produced acetaldehyde, operating via a similar mechanism to that found after alcoholic beverage ingestion. In addition, topically applied ethanol acts as a skin penetration enhancer and may facilitate the transdermal absorption of xenobiotics (e.g. carcinogenic contaminants in cosmetic formulations). Ethanol use is associated with skin irritation or contact dermatitis, especially in humans with an aldehyde dehydrogenase (ALDH) deficiency. After regular application of ethanol on the skin (e.g. in the form of hand disinfectants) relatively low but measurable blood concentrations of ethanol and its metabolite acetaldehyde may occur, which are, however, below acute toxic levels. Only in children, especially through lacerated skin, can percutaneous toxicity occur. As there might be industry bias in many studies about the safety of topical ethanol applications, as well as a general lack of

  15. Safety evaluation of topical applications of ethanol on the skin and inside the oral cavity.

    PubMed

    Lachenmeier, Dirk W

    2008-01-01

    Ethanol is widely used in all kinds of products with direct exposure to the human skin (e.g. medicinal products like hand disinfectants in occupational settings, cosmetics like hairsprays or mouthwashes, pharmaceutical preparations, and many household products). Contradictory evidence about the safety of such topical applications of the alcohol can be found in the scientific literature, yet an up-to-date risk assessment of ethanol application on the skin and inside the oral cavity is currently lacking.The first and foremost concerns of topical ethanol applications for public health are its carcinogenic effects, as there is unambiguous evidence for the carcinogenicity of ethanol orally consumed in the form of alcoholic beverages. So far there is a lack of evidence to associate topical ethanol use with an increased risk of skin cancer. Limited and conflicting epidemiological evidence is available on the link between the use of ethanol in the oral cavity in the form of mouthwashes or mouthrinses and oral cancer. Some studies pointed to an increased risk of oral cancer due to locally produced acetaldehyde, operating via a similar mechanism to that found after alcoholic beverage ingestion.In addition, topically applied ethanol acts as a skin penetration enhancer and may facilitate the transdermal absorption of xenobiotics (e.g. carcinogenic contaminants in cosmetic formulations). Ethanol use is associated with skin irritation or contact dermatitis, especially in humans with an aldehyde dehydrogenase (ALDH) deficiency.After regular application of ethanol on the skin (e.g. in the form of hand disinfectants) relatively low but measurable blood concentrations of ethanol and its metabolite acetaldehyde may occur, which are, however, below acute toxic levels. Only in children, especially through lacerated skin, can percutaneous toxicity occur.As there might be industry bias in many studies about the safety of topical ethanol applications, as well as a general lack of

  16. Topical application of a novel, hydrophilic gamma-tocopherol derivative reduces photo-inflammation in mice skin.

    PubMed

    Yoshida, Emiko; Watanabe, Tatsuya; Takata, Jiro; Yamazaki, Akihiko; Karube, Yoshiharu; Kobayashi, Shizuko

    2006-07-01

    We previously demonstrated that a novel hydrophilic gamma-tocopherol (gamma-Toc) derivative, gamma-tocopherol-N,N-dimethylglycinate hydrochloride (gamma-TDMG) converts to gamma-Toc in the mouse skin and has a higher bioavailability than gamma-Toc itself. In the present study, we determined whether gamma-TDMG could reduce photo-inflammation in mouse skin, and compared its effectiveness to that of alpha-Toc acetate (alpha-TA). Topical pre- or post-application of 5% gamma-TDMG significantly reduced the formation of edema and tempered the increase in cyclooxygenase-2 (COX-2)-catalyzed synthesis of prostaglandin E2 (PGE2) that were induced by a single dose of UV irradiation of 2 kJ/m2 (290-380 nm, maximum 312 nm). The pre-treatment of mouse skin with 10% alpha-TA had the same anti-inflammatory effect as did gamma-TDMG. In spite of same having the ability to reduce PGE2 levels, the effect of gamma-TDMG pre-treatment on the inhibition of COX-2 mRNA/protein expression was less than that seen with 10% alpha-TA. In contrast, the increase in COX-2 activity seen after UV exposure was reduced more by gamma-TDMG than by alpha-TA, suggesting that the reduction in PGE2 levels might have been due to the direct inhibition of COX-2 activity by gamma-TDMG-derived gamma-Toc. Both Toc derivatives strongly suppressed inducible nitric oxide synthase (iNOS) mRNA expression and nitric oxide (NO) production, both of which play important roles in UV-induced inflammation. Both derivatives also significantly reduced lipid peroxidation in response to UV exposure, though gamma-TDMG's ability in this regard was less than that seen with alpha-TA, which correlated with their abilities to suppress COX-2 expression. Thus, the gamma-TDMG-derived gamma-Toc acts as an antioxidant, suppresses iNOS expression and directly inhibits COX-2 activity, all of which likely play a role in mediating its suppressive effects on photo-inflammation. Our data further suggest that the topical application of gamma-TDMG, a

  17. Chemical ultraviolet absorbers topically applied in a skin barrier mimetic formulation remain in the outer stratum corneum of porcine skin.

    PubMed

    Haque, T; Crowther, J M; Lane, M E; Moore, D J

    2016-08-20

    The objective of the present study was to evaluate the fate of three chemical sunscreens, isoamyl p-methoxycinnamate (IPMC), diethylamino hydroxybenzoyl hexyl benzoate (DHHB), and bis-ethylhexylphenol methoxyphenyl triazine (BEMT), topically applied to mammalian skin from a skin barrier mimetic oil-in-water formulation. High Performance Liquid Chromatography (HPLC) methods were developed for the analysis of each molecule and validated. Franz cell permeation studies were conducted following application of finite doses of the formulations to excised porcine skin. A vehicle formulation containing no sunscreens was evaluated as a control. Permeation studies were conducted for 12h after which full mass balance studies were carried out. Analysis of individual UV sunscreens was achieved with HPLC following application of the formulation to the skin with no interference from the vehicle components. No skin permeation of any of the chemical sunscreens was evident after 12h. While sunscreens were detected in up to 12 tape strips taken from the SC, 87% or more of the applied doses recovered in the first 5 tape strips. When corrected for the amount of protein removed per tape strip this corresponded to a penetration depth in porcine stratum corneum of ∼1.7μm. Mass balance studies indicated total recovery values were within accepted guidelines for cosmetic formulations. Overall, only superficial penetration into the SC was observed for each compound. These findings are consistent with the physicochemical properties of the selected UV absorbing molecules and their formulation into an ordered biomimetic barrier formulation thus support their intended use in topical consumer formulations designed to protect from UV exposure. To our knowledge this is the first report of depth profiling of chemical sunscreens in the SC that combines tape stripping and protein determination following in vitro Franz cell studies. PMID:27321112

  18. Comparative Efficacy and Patient Preference of Topical Anaesthetics in Dermatological Laser Treatments and Skin Microneedling

    PubMed Central

    Chiang, Yi Zhen; Al-Niaimi, Firas; Madan, Vishal

    2015-01-01

    Background: Topical anaesthetics are effective for patients undergoing superficial dermatological and laser procedures. Our objective was to compare the efficacy and patient preference of three commonly used topical anaesthetics: (2.5% lidocaine/2.5% prilocaine cream (EMLA®), 4% tetracaine gel (Ametop™) and 4% liposomal lidocaine gel (LMX4®)) in patients undergoing laser procedures and skin microneedling. Settings and Design: This was a prospective, double-blind study of patients undergoing laser and skin microneedling procedures at a laser unit in a tertiary referral dermatology centre. Materials and Methods: All 29 patients had three topical anaesthetics applied under occlusion for 1 hour prior to the procedure, at different treatment sites within the same anatomical zone. A self-assessment numerical pain rating scale was given to each patient to rate the pain during the procedure and each patient was asked to specify their preferred choice of topical anaesthetic at the end of the procedure. Statistical Analysis: Parametric data (mean pain scores and frequency of topical anaesthetic agent of choice) were compared using the paired samples t-test. A P-value of ≤0.05 was considered as statistically significant. Results and Conclusions: Patients reported a mean (±SD; 95% confidence interval) pain score of 5 (±2.58; 3.66-6.46) with Ametop™, 4.38 (±2.53; 2.64-4.89) with EMLA® and 3.91 (±1.95; 2.65-4.76) with LMX4®. There was no statistically significant difference in pain scores between the different topical anaesthetics. The majority of patients preferred LMX4® as their choice of topical anaesthetic for dermatological laser and skin microneedling procedures. PMID:26644737

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

    PubMed

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

    2016-01-01

    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

  20. Evaluation of Skin Permeation of β-blockers for Topical Drug Delivery

    PubMed Central

    Chantasart, Doungdaw; Hao, Jinsong; Li, S. Kevin

    2013-01-01

    Purpose β-Blockers have recently become the main form of treatment of infantile hemangiomas. Due to the potential systemic adverse effects of β-blockers, topical skin treatment of the drugs is preferred. However, the effect and mechanism of dosage form pH upon skin permeation of these weak bases is not well understood. To develop an effective topical skin delivery system for the β-blockers, the present study evaluated skin permeation of β-blockers propranolol, betaxolol, timolol, and atenolol. Methods Experiments were performed in side-by-side diffusion cells with human epidermal membrane (HEM) in vitro to determine the effect of donor solution pH upon the permeation of the β-blockers across HEM. Results The apparent permeability coefficients of HEM for the β-blockers increased with their lipophilicity, suggesting the HEM lipoidal pathway as the main permeation mechanism of the β-blockers. The pH in the donor solution was a major factor influencing HEM permeation for the β-blockers with a 2- to 4-fold increase in the permeability coefficient per pH unit increase. This permeability versus pH relationship was found to deviate from theoretical predictions, possibly due to the effective stratum corneum pH being different from the pH in the donor solution. Conclusions The present results suggest the possibility of topical treatment of hemangioma using β-blockers. PMID:23208385

  1. In vivo spectrophotometric evaluation of skin barrier recovery after topical application of soybean phytosterols.

    PubMed

    Puglia, Carmelo; Bonina, Francesco

    2008-01-01

    The skin's uppermost thin layer, stratum corneum, plays a crucial role in protecting the body against unwanted influences from the environment. Disruption of the stratum corneum, by tape stripping or chemical injury, results in epidermal recovery of the skin barrier. Soy phytosterols are widely used in the cosmetic field as active ingredients in creams and lipsticks. Furthermore, they deserve an important place among nutracosmeceuticals; in fact, after their absorption from the diet they are transferred from the plasma to the skin, playing an important role in the constitution of skin surface lipids. The aim of the present work was to study the effect of the topical application of soybean phytosterols on skin barrier recovery in human volunteers using the extent of methyl nicotinate (MN)-induced erythema in damaged skin as a parameter to evaluate the rate of stratum corneum recovery. MN was chosen as an erythematogenous substance for its capability to cause an erythema whose intensity and duration are proportional to the quantity of the substance that has entered the living epidermis over time. MN-induced erythema was monitored using reflectance spectrophotometry as a noninvasive instrumental technique. The results show clearly that soy phytosterols exert positive results on skin repair; in fact, three days after tape stripping, the sites treated with a formulation containing phytosterols showed an appreciable recovery of barrier function compared to those treated with a vehicle control without soy phytosterols.

  2. Disposition of benzyl alcohol after topical application to human skin in vitro.

    PubMed

    Saiyasombati, Penpan; Kasting, Gerald B

    2003-10-01

    Dissipation of a volatile compound or mixture from the skin surface after topical application involves both diffusion and evaporation. This report presents a detailed test of a previously described first-order kinetic approach to modeling this problem. Modified Franz diffusion cells fitted with a vapor trap were used to obtain absorption and evaporation data for benzyl alcohol (1% solution in ethanol) after application to human skin in vitro. Airflow over the skin surface (upsilon) was controlled in the experiment and accounted for in the model by allowing the evaporation rate constant(s) to vary as a function of upsilon. A linear dependence was found over the working range of the system, 10-100 mL/min. Three kinetic models were developed, all of which satisfactorily correlated cumulative absorption and evaporation results over the full range of upsilon (n = 120, s = 4-5%, r2 = 0.98-0.99). One of these was the model presented previously, in which all dissipation occurs from a single skin compartment. However, more details of the evaporation and absorption profiles could be accounted for by means of two-compartment models that explicitly consider the surface film present in the early stages post-application. The latter models seem to be better candidates for describing the time evolution of the volatile mixture evolving from the skin surface after topical application of, e.g., a complex fragrance or perfume.

  3. Topical use of sodium cromoglicate (cromolyn sodium) to treat atopic dermatitis and other skin allergies.

    PubMed

    Zur, Eyal

    2012-01-01

    Sodium cromoglicate (cromolyn sodium) is a very well-known medicine that has been used for many years for various allergic conditions. The topical use of this medicine is less known, and there are no commercial medicines of cream, gel, or lotion in most of the world. This article summarizes the clinical data accumulated from seventeen trials that checked the topical efficacy and safety of sodium cromoglicate and analyzes the clinical implementations of this medicine in the topical treatment of atopic dermatitis and other skin allergies. In addition, this article analyzes the various formulations that have been used in the clinical trials in an attempt to find the optimal formulation. The topical use of sodium cromoglicate seemed to have a promising potential, and implementing the data of this article can allow the compounding pharmacist a very interesting professional activity in very common and widespread allergic pathologies.

  4. Topical alpha-selective p38 MAP kinase inhibition reduces acute skin inflammation in guinea pig

    PubMed Central

    Medicherla, Satyanarayana; Ma, Jing Ying; Reddy, Mamtha; Esikova, Irina; Kerr, Irene; Movius, Fabiola; Higgins, Linda S; Protter, Andrew A

    2010-01-01

    Certain skin pathologies, including psoriasis, are thought to be immune-mediated inflammatory diseases. Available literature clearly indicates the involvement of inflammatory cells (neutrophils, T cells, and macrophages), their cytokines, and the p38 mitogen-activated protein kinase (MAPK) signaling pathway in the pathophysiology of psoriasis. Neutrophils play an important role in the formation of acute inflammatory changes in psoriasis. Acute inflammation or acute flares in psoriasis remain poorly addressed in clinical medicine. In this communication, we first establish a simple and reproducible model for studying neutrophil-mediated acute skin inflammation. Using the hairless guinea pig, due to the similarity of skin architecture to that of human, acute inflammation was induced with an intradermal injection of 50 μg/mL lipopolysaccharide (LPS) in 50 μL solution. Myeloperoxidase (MPO) activity was measured by MPO-positive neutrophils and shown to increase for 24-hours post-injection. Simultaneously, the level of phosphorylated p38 MAPK was documented for 48-hours post-LPS injection in the skin. Next, we used this model to examine the therapeutic potential of an α-selective p38 MAPK inhibitor, SCIO-469. A comparison of topical application of SCIO-469 at 5 mg/mL or 15 mg/mL to vehicle revealed that SCIO-469 dose-dependently reduces acute skin inflammation and that this effect is statistically significant at the higher dose. Further examination of tissues that received this dose also revealed statistically significant reduction of MPO activity, phosphorylated p38 MAPK, interleukin-6, and cyclooxygenase-2. These data suggest that the α-selective p38 MAPK inhibitor, SCIO-469, acts as a topical anti-inflammatory agent via the p38 MAPK pathway to reduce neutrophil induced acute inflammation in the skin. These observations suggest that α-selective p38 MAPK inhibition may be an effective therapeutic strategy to manage acute skin inflammation PMID:22096353

  5. Tumorigenesis of diesel exhaust, gasoline exhaust, and related emission extracts on SENCAR mouse skin

    SciTech Connect

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

    1980-01-01

    The tumorigenicity of diesel exhaust particulate emissions was examined using a sensitive mouse skin tumorigenesis model (SENCAR). The tumorigenic potency of particulate emissions from diesel, gasoline, and related emission sources was compared.

  6. Percutaneous characterization of the insect repellent DEET and the sunscreen oxybenzone from topical skin application

    SciTech Connect

    Kasichayanula, Sreeneeranj; House, James D.; Wang Tao; Gu Xiaochen

    2007-09-01

    The synergistic percutaneous enhancement between insect repellent DEET and sunscreen oxybenzone has been proven in our laboratory using a series of in vitro diffusion studies. In this study, we carried out an in vivo study to characterize skin permeation profiles from topical skin application of three commercially available repellent and sunscreen preparations. The correlation between skin disposition and drug metabolism was attempted by using data collected. Both DEET and oxybenzone permeated across the skin after the application and achieved substantial systemic absorption. Combined use of DEET and oxybenzone significantly enhanced the percutaneous penetration percentages (ranging 36-108%) due to mutual enhancement effects. Skin disposition indicated that DEET produced a faster transdermal permeation rate and higher systemic absorption extent, but oxybenzone formed a concentrated depot within the skin and delivered the content slowly over the time. In vivo AUC{sub P}/MRT of DEET and oxybenzone was increased by 37%/17% and 63%/10% when the two compounds were used together. No DEET was detected from the urine samples 48 h after the application. Tape stripping seemed to be a satisfactory approach for quantitative assessment of DEET and oxybenzone penetration into the stratum corneum. It was also concluded that pharmacological and toxicological perspectives from concurrent application of insect repellent and sunscreen products require further evaluation to ensure use efficacy and safety of these common consumer healthcare products.

  7. Preliminary investigations of rat skin after topical application of optical clearing agent

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Zhu, Dan

    2011-03-01

    The tissue optical clearing technique based on immersion of tissues into optical clearing agents (OCAs) can enhance the penetration depth of light in tissues, thus improve the capabilities of noninvasive optical diagnosis and therapeutic treatment. However, the optical clearing efficiency of skin caused by topical application of OCAs usually suffers from the barrier of stratum corneum and epithelium. The addition of chemical penetration enhancers to OCAs could significantly improve the optical clearing of skin, but the investigations on their safety are seldom concerned. In this study, based on the direct observation and histological examinations, the short-term and long-term effects of the mixture of PEG-400 and Thiazone on morphology and microstructure of in vivo rat skin were investigated. The results demonstrated that, in the first week, the hair growth was stunted, some degree of abnormal thickens and vacuoles occurred at the epidermis layer, and the collagen arranged denser. After 2 week, the morphology and microstructure of rat skin was completely recovered. It means that there is no long-term effect on rat skin by the mixture of PEG-400 and Thiazone. In addition, this work provides a useful method for assessing the safety of OCAs to skin.

  8. Preliminary investigations of rat skin after topical application of optical clearing agent

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Zhu, Dan

    2010-10-01

    The tissue optical clearing technique based on immersion of tissues into optical clearing agents (OCAs) can enhance the penetration depth of light in tissues, thus improve the capabilities of noninvasive optical diagnosis and therapeutic treatment. However, the optical clearing efficiency of skin caused by topical application of OCAs usually suffers from the barrier of stratum corneum and epithelium. The addition of chemical penetration enhancers to OCAs could significantly improve the optical clearing of skin, but the investigations on their safety are seldom concerned. In this study, based on the direct observation and histological examinations, the short-term and long-term effects of the mixture of PEG-400 and Thiazone on morphology and microstructure of in vivo rat skin were investigated. The results demonstrated that, in the first week, the hair growth was stunted, some degree of abnormal thickens and vacuoles occurred at the epidermis layer, and the collagen arranged denser. After 2 week, the morphology and microstructure of rat skin was completely recovered. It means that there is no long-term effect on rat skin by the mixture of PEG-400 and Thiazone. In addition, this work provides a useful method for assessing the safety of OCAs to skin.

  9. Covalent binding of benzo(a)pyrene diol epoxide to DNA of mouse skin: in vivo persistence of adducts formation

    SciTech Connect

    Shugart, L.

    1985-01-01

    In the first 9 d after topical application of a single dose of benzo(a)pyrene to the dorsal skin of C/sub 3/H mice, the half-lives of benzo(a)pyrene diol epoxide-DNA adducts and of DNA were determined to be approximately 5 d. These data indicate that, in proliferating mouse skin, benzo(a)pyrene diol epoxide-DNA lesions are not repaired, but are diluted from the genome at a rate equivalent to DNA turnover (i.e., replication versus degradation). Subsequent to this initial period, benzo(a)pyrene diol epoxide-DNA adduct removal continues, but at a much reduced rate. At 30 d posttreatment with benzo(a)pyrene, approximately 15% of the adducts are still detectable; however, their half-lives had increased to 30 d. Similar experiments with a hairless mouse showed that, although the amount of adduct formation was lower initially, the kinetics of aduct disappearance and persistence were essentially the same as found with the C/sub 3/H mouse. The data obtained in this work are consistent with the hypothesis that benzo(a)pyrene diol epoxide adducts persist in a subpopulation of skin cells long after their disappearance by DNA turnover would predict.

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

    PubMed

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

    2013-09-01

    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.

  11. Lipid nanoparticles for improved topical application of drugs for skin diseases.

    PubMed

    Schäfer-Korting, Monika; Mehnert, Wolfgang; Korting, Hans-Christian

    2007-07-10

    Due to the lower risk of systemic side effects topical treatment of skin disease appears favourable, yet the stratum corneum counteracts the penetration of xenobiotics into viable skin. Particulate carrier systems may mean an option to improve dermal penetration. Since epidermal lipids are found in high amounts within the penetration barrier, lipid carriers attaching themselves to the skin surface and allowing lipid exchange between the outermost layers of the stratum corneum and the carrier appear promising. Besides liposomes, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been studied intensively. Here we describe the potential of these carrier systems and compare the dermal uptake from SLN and NLC to the one of alternative vehicle systems. A special focus is upon the interactions of active ingredients and the lipid matrix as well as the quantification of dermal penetration. PMID:17544165

  12. Percutaneous absorption kinetics of topical metronidazole formulations in vitro in the human cadaver skin model.

    PubMed

    Elewski, Boni E

    2007-01-01

    Topical formulations containing identical active agents are available in various vehicles and concentrations, which may affect percutaneous absorption. This study was undertaken to evaluate the in vitro percutaneous absorption pharmacokinetics of metronidazole in different vehicles and concentrations as the active agent in 6 topical formulations. Formulations were applied to sections from 3 cadaver skin donors, and percutaneous absorption of metronidazole was measured over a 48-h test period through the finite dose technique and the use of Franz diffusion cells. Metronidazole penetrates into and through human cadaver skin. Data show the general ranking of delivery of similar concentrations of metronidazole according to vehicle as cream > lotion > gel. The 48-h penetration of metronidazole in the human cadaver skin model was greatest with cream formulations and lowest with gel formulations. These results reveal the importance of the vehicle selected for penetration of metronidazole into the skin. The relevant target zone in rosacea is the dermis because this is the area where inflammation takes place. Additional studies are warranted to examine absorption of metronidazole into the relevant target zone and the correlation of absorption with efficacy.

  13. Topical PDT in the Treatment of Benign Skin Diseases: Principles and New Applications

    PubMed Central

    Kim, Miri; Jung, Haw Young; Park, Hyun Jeong

    2015-01-01

    Photodynamic therapy (PDT) uses a photosensitizer, light energy, and molecular oxygen to cause cell damage. Cells exposed to the photosensitizer are susceptible to destruction upon light absorption because excitation of the photosensitizing agents leads to the production of reactive oxygen species and, subsequently, direct cytotoxicity. Using the intrinsic cellular heme biosynthetic pathway, topical PDT selectively targets abnormal cells, while preserving normal surrounding tissues. This selective cytotoxic effect is the basis for the use of PDT in antitumor treatment. Clinically, PDT is a widely used therapeutic regimen for oncologic skin conditions such as actinic keratosis, squamous cell carcinoma in situ, and basal cell carcinoma. PDT has been shown, under certain circumstances, to stimulate the immune system and produce antibacterial, and/or regenerative effects while protecting cell viability. Thus, it may be useful for treating benign skin conditions. An increasing number of studies support the idea that PDT may be effective for treating acne vulgaris and several other inflammatory/infective skin diseases, including psoriasis, rosacea, viral warts, and aging-related changes. This review provides an overview of the clinical investigations of PDT and discusses each of the essential aspects of the sequence: its mechanism of action, common photosensitizers, light sources, and clinical applications in dermatology. Of the numerous clinical trials of PDT in dermatology, this review focuses on those studies that have reported remarkable therapeutic benefits following topical PDT for benign skin conditions such as acne vulgaris, viral warts, and photorejuvenation without causing severe side effects. PMID:26404243

  14. Topical PDT in the Treatment of Benign Skin Diseases: Principles and New Applications.

    PubMed

    Kim, Miri; Jung, Haw Young; Park, Hyun Jeong

    2015-01-01

    Photodynamic therapy (PDT) uses a photosensitizer, light energy, and molecular oxygen to cause cell damage. Cells exposed to the photosensitizer are susceptible to destruction upon light absorption because excitation of the photosensitizing agents leads to the production of reactive oxygen species and, subsequently, direct cytotoxicity. Using the intrinsic cellular heme biosynthetic pathway, topical PDT selectively targets abnormal cells, while preserving normal surrounding tissues. This selective cytotoxic effect is the basis for the use of PDT in antitumor treatment. Clinically, PDT is a widely used therapeutic regimen for oncologic skin conditions such as actinic keratosis, squamous cell carcinoma in situ, and basal cell carcinoma. PDT has been shown, under certain circumstances, to stimulate the immune system and produce antibacterial, and/or regenerative effects while protecting cell viability. Thus, it may be useful for treating benign skin conditions. An increasing number of studies support the idea that PDT may be effective for treating acne vulgaris and several other inflammatory/infective skin diseases, including psoriasis, rosacea, viral warts, and aging-related changes. This review provides an overview of the clinical investigations of PDT and discusses each of the essential aspects of the sequence: its mechanism of action, common photosensitizers, light sources, and clinical applications in dermatology. Of the numerous clinical trials of PDT in dermatology, this review focuses on those studies that have reported remarkable therapeutic benefits following topical PDT for benign skin conditions such as acne vulgaris, viral warts, and photorejuvenation without causing severe side effects. PMID:26404243

  15. Characterization of the serotoninergic system in the C57BL/6 mouse skin.

    PubMed

    Slominski, Andrzej; Pisarchik, Alexander; Semak, Igor; Sweatman, Trevor; Wortsman, Jacobo

    2003-08-01

    We showed expression of the tryptophan hydroxylase gene and of tryptophan hydroxylase protein immunoreactivity in mouse skin and skin cells. Extracts from skin and melanocyte samples acetylated serotonin to N-acetylserotonin and tryptamine to N-acetyltryptamine. A different enzyme from arylalkylamine N-acetyltransferase mediated this reaction, as this gene was defective in the C57BL6 mouse, coding predominantly for a protein without enzymatic activity. Serotonin (but not tryptamine) acetylation varied according to hair cycle phase and anatomic location. Serotonin was also metabolized to 5-hydroxytryptophol and 5-hydroxyindole acetic acid, probably through stepwise transformation catalyzed by monoamine oxidase, aldehyde dehydrogenase and aldehyde reductase. Activity of the melatonin-forming enzyme hydroxyindole-O-methyltransferase was notably below detectable levels in all samples of mouse corporal skin, although it was detectable at low levels in the ears and in Cloudman melanoma (derived from the DBA/2 J mouse strain). In conclusion, mouse skin has the molecular and biochemical apparatus necessary to produce and metabolize serotonin and N-acetylserotonin, and its activity is determined by topography, physiological status of the skin, cell type and mouse strain. PMID:12899690

  16. Photoeffects of near ultraviolet light upon a polycyclic aromatic hydrocarbon exposed to mouse skin microsomes

    SciTech Connect

    Peirano, W.B.

    1991-01-01

    Near ultraviolet (UV) light has been reported to both enhance and inhibit the tumor incidence in mice dermally exposed to benzo(a)pyrene (BaP) or polycyclic aromatic hydrocarbon (PAH) mixtures. Near UV light interacts with PAHs producing a variety of oxygenated products such as phenols, endoperoxides and quinones. However, little is known about BaP products formed from near UV irradiation of BaP-exposed mouse skin. Therefore, [sup 14]C-BaP was incubated with 3-methylcholanthrene (3-MC) induced C[sub 3]H/HeJ and DBA/2J mouse skin microsomes with or without a 365 nm light source. The results indicated that the concurrent 365 nm light irradiation of induced mouse skin microsomes and BaP greatly enhanced the total conversion of BaP to its products, approximately 3-fold for the C[sub 3]H/HeJ and approximately 7-fold for the DBA/2J mouse microsomes, compared to the induced mouse skin microsomes and BaP alone. HPLC analyses of organic extracts indicated a more than additive enhancement of the formation of most of the individual cochromatographed BaP metabolites due to the combined interaction of 365 nm light with BaP and skin microsomes. Similar interactions were observed using benz(a)anthracene (BaA) in this system. These data show that near UV light alters the metabolic profile of PAHs produced by mouse skin microsomes.

  17. A Novel Matrikine-Like Micro-Protein Complex (MPC) Technology for Topical Skin Rejuvenation.

    PubMed

    Dreher, Frank

    2016-04-01

    This randomized, controlled, investigator-blinded study performed by an independent research organization evaluated the appearance of periorbital and perioral wrinkles following twice-daily application of a specific blend of matrikines and matrikine-like synthetic peptides for skin rejuvenation over a 6-month period. Fine lines and wrinkles of 133 women, aged 38 years to 65 years, were assessed by an independent expert evaluator using a 5-point visual analogue score. Subjects were divided into 3 groups and randomized to receive either the matrikine-based technology (MPC) or 1 of the 2 materials containing traditional growth factors. Test materials were well tolerated, and all 3 significantly reduced the appearance of periorbital and perioral wrinkles after 3 and 6 months. In the group receiving the matrikine-based technology, periorbital wrinkles improved (≥ 1 unit) in 28% of subjects after 1 month, in 65% after 3 months, and in 81% after 6 months. Perioral wrinkles improved (≥ 1 unit) in 39% of subjects after 1 month, in 41% after 3 months, and in 59% after 6 months. Improvements in skin firmness, tactile roughness, and pore appearance were also observed with each test material. Use of MPC was associated with significantly improved skin elasticity after 2 months (20%) and at 6 months (16%), whereas the comparator materials had no significant effects on elasticity. This study demonstrates that topical use of a specific blend of matrikines and matrikine-like peptides is suitable for skin rejuvenation. It also provides evidence that topical use of this novel technology provides comparable results to other technologies that use traditional growth factors for skin rejuvenation, with an additional potential benefit of improved skin elasticity. PMID:27050701

  18. Fluorescence spectroscopy: a rapid, noninvasive method for measurement of skin surface thickness of topical agents.

    PubMed

    Rhodes, L E; Diffey, B L

    1997-01-01

    We report the quantification of skin surface thickness of topical agents by in vivo fluorescence spectroscopy, and demonstrate its potential uses for assessment of application technique and substantivity. A series of studies were performed on forearm skin of eight normal subjects using three creams which have intrinsic fluorescence: a sunscreen (Neutrogena SPF15 waterproof cream), an antiseptic (Hewlett's cream) and a steroid (Trimovate (clobetasone butyrate) cream). Initially, the dose-response relationship was established for each agent by applying a series of five doses (0.5-8 microliters/cm2) and measuring cream fluorescence using appropriate excitation and emission wavelengths. Next, the influence of application technique was examined by comparing light application of cream with firm rubbing. Substantivity of the three creams was assessed on dry skin by taking fluorescence measurements over 8 h. Finally, water resistance of 2 microliters/cm2 of sunscreen and antiseptic cream were compared by measuring fluorescence after each of four water immersions. The fluorescence intensity was strongly correlated with the logarithm of surface density. r = 1.0, 0.92 and 0.98 for sunscreen, antiseptic and steroid creams, respectively, allowing derivation of a simple expression for equivalent thickness. Surface thickness of each cream was lower following firm rubbing compared with light application (P < 0.01). The rate constants for reduction of surface density of the three creams with time on dry skin were not significantly different. However, on washed skin, the rate constant was higher for Hewlett's than Neutrogena cream (0.503 and 0.243 h. respectively, P = 0.02), with a higher rate for each cream on wet compared with dry skin (P < 0.001). Hence, fluorescence spectroscopy is a simple, rapid method for measurement of cream thickness in vivo. The many potential applications in dermatology include quantitative assessment of application technique and substantivity of topical

  19. Management of skin tears and stage II skin ulcers with two topical regimens: a study of cost minimization.

    PubMed

    Villasin, J V; Vinson, J A; Igoe, M B; Hendricks, L

    1996-01-01

    A health-economic study of newly formed skin tears and stage II ulcers used an unblinded, comparative, parallel-group design to evaluate two topical regimens as to time required for complete healing and assessment of cost minimization. Thirty-six elderly patients, at risk for developing indolent wounds of the skin and underlying tissues, were assigned to receive either a saline spray and a topical antibiotic ointment (TAM, n = 14) or Dermagran Spray and Dermagran Ointment (DSO, n = 22). The 76 wounds that appeared in these patients had comparable pretreatment surface areas of 3.73 +/- 0.96 cm2 in the DSO group versus 5.57 +/- 1.13 cm2 in the TAM group (P = NS). All wounds were treated twice daily, starting within 24 hours of their appearance, until complete healing. The 19 wounds in the TAM group healed within 48.0 +/- 25.3 days versus 15.4 +/- 1.9 days for the 57 wounds in the DSO group (P < .05). The cost of wound management for a given patient was calculated by adding the costs of nursing labor and the amount of product consumed to effect complete healing. To this end, the cost of the TAM regimen was $323.23 +/- 171.70 versus $104.75 +/- 12.92 for the DSO regimen (P < .05). Results are presented in light of the increasing pressure on long-term care facilities to provide effective and affordable treatment.

  20. Human skin penetration and local effects of topical nano zinc oxide after occlusion and barrier impairment.

    PubMed

    Leite-Silva, V R; Sanchez, W Y; Studier, H; Liu, D C; Mohammed, Y H; Holmes, A M; Ryan, E M; Haridass, I N; Chandrasekaran, N C; Becker, W; Grice, J E; Benson, H A E; Roberts, M S

    2016-07-01

    Public health concerns continue to exist over the safety of zinc oxide nanoparticles that are commonly used in sunscreen formulations. In this work, we assessed the effects of two conditions which may be encountered in everyday sunscreen use, occlusion and a compromised skin barrier, on the penetration and local toxicity of two topically applied zinc oxide nanoparticle products. Caprylic/capric triglyceride (CCT) suspensions of commercially used zinc oxide nanoparticles, either uncoated or with a silane coating, were applied to intact and barrier impaired skin of volunteers, without and with occlusion for a period of six hours. The exposure time was chosen to simulate normal in-use conditions. Multiphoton tomography with fluorescence lifetime imaging was used to noninvasively assess zinc oxide penetration and cellular metabolic changes that could be indicative of toxicity. We found that zinc oxide nanoparticles did not penetrate into the viable epidermis of intact or barrier impaired skin of volunteers, without or with occlusion. We also observed no apparent toxicity in the viable epidermis below the application sites. These findings were validated by ex vivo human skin studies in which zinc penetration was assessed by multiphoton tomography with fluorescence lifetime imaging as well as Zinpyr-1 staining and toxicity was assessed by MTS assays in zinc oxide treated skin cryosections. In conclusion, applications of zinc oxide nanoparticles under occlusive in-use conditions to volunteers are not associated with any measurable zinc oxide penetration into, or local toxicity in the viable epidermis below the application site.

  1. Human skin penetration and local effects of topical nano zinc oxide after occlusion and barrier impairment.

    PubMed

    Leite-Silva, V R; Sanchez, W Y; Studier, H; Liu, D C; Mohammed, Y H; Holmes, A M; Ryan, E M; Haridass, I N; Chandrasekaran, N C; Becker, W; Grice, J E; Benson, H A E; Roberts, M S

    2016-07-01

    Public health concerns continue to exist over the safety of zinc oxide nanoparticles that are commonly used in sunscreen formulations. In this work, we assessed the effects of two conditions which may be encountered in everyday sunscreen use, occlusion and a compromised skin barrier, on the penetration and local toxicity of two topically applied zinc oxide nanoparticle products. Caprylic/capric triglyceride (CCT) suspensions of commercially used zinc oxide nanoparticles, either uncoated or with a silane coating, were applied to intact and barrier impaired skin of volunteers, without and with occlusion for a period of six hours. The exposure time was chosen to simulate normal in-use conditions. Multiphoton tomography with fluorescence lifetime imaging was used to noninvasively assess zinc oxide penetration and cellular metabolic changes that could be indicative of toxicity. We found that zinc oxide nanoparticles did not penetrate into the viable epidermis of intact or barrier impaired skin of volunteers, without or with occlusion. We also observed no apparent toxicity in the viable epidermis below the application sites. These findings were validated by ex vivo human skin studies in which zinc penetration was assessed by multiphoton tomography with fluorescence lifetime imaging as well as Zinpyr-1 staining and toxicity was assessed by MTS assays in zinc oxide treated skin cryosections. In conclusion, applications of zinc oxide nanoparticles under occlusive in-use conditions to volunteers are not associated with any measurable zinc oxide penetration into, or local toxicity in the viable epidermis below the application site. PMID:27131753

  2. Topical application of gamma-tocopherol derivative prevents UV-induced skin pigmentation.

    PubMed

    Kuwabara, Yuka; Watanabe, Tatsuya; Yasuoka, Shingo; Fukui, Kohsuke; Takata, Jiro; Karube, Yoshiharu; Okamoto, Yuko; Asano, Shin; Katoh, Eiko; Tsuzuki, Toshi; Kobayashi, Shizuko

    2006-06-01

    We previously reported that a novel hydrophilic gamma-tocopherol (gamma-Toc) derivative, gamma-tocopheryl-N,N-dimethylglycinate hydrochloride (gamma-TDMG) gets converted to the antioxidant gamma-Toc in skin. We also found that this derivative displayed greater bioavailability than gamma-Toc itself. In the present study, we determined whether gamma-TDMG could reduce UV-induced skin pigmentation in brownish guinea pigs. gamma-TDMG (0.1 or 0.5%) was topically applied to the skin before and after it was exposed to UVB plus UVA (3 times/week for 1 week), and then 10 times/week for 4 weeks thereafter. Treatment with 0.5% gamma-TDMG resulted in significant skin lightening (70% of the pigmentation of irradiated controls). We also found that melanin synthesis was dose-dependently inhibited by gamma-TDMG in murine B16 melanoma cells. When gamma-TDMG or kojic acid (250 microM) were added to homogenates of B16 melanoma cells, their tyrosinase activity was significantly inhibited by approximately 40% and 75%, respectively. Mushroom tyrosinase activity was significantly inhibited by 200 microM gamma-Toc and kojic acid, but not gamma-TDMG. When B16 cells were incubated with 250 microM gamma-TDMG for 24 or 48 h, their intracellular gamma-Toc concentrations rose over 100 fold to 10.5 and 11.2 nmol/10(6) cells, respectively, suggesting that gamma-TDMG was rapidly converted to gamma-Toc in these cells and that their reduced melanin synthesis may have been due to the activity of gamma-Toc. Our data further suggest that the topical application of gamma-TDMG may be efficacious in preventing photo-induced skin pigmentation in humans.

  3. Topical penetration of commercial salicylate esters and salts using human isolated skin and clinical microdialysis studies

    PubMed Central

    Cross, Sheree E; Anderson, Chris; Roberts, Michael S

    1998-01-01

    Aims The penetration of active ingredients from topically applied anti-inflammatory pharmaceutical products into tissues below the skin is the basis of their therapeutic efficacy. There is still controversy as to whether these agents are capable of direct penetration by diffusion through the tissues or whether redistribution in the systemic circulation is responsible for their tissue deposition below the application site. Methods The extent of direct penetration of salicylate from commercial ester and salt formulations into the dermal and subcutaneous tissue of human volunteers was determined using the technique of cutaneous microdialysis. We also examined differences in the extent of hydrolysis of the methylester of salicylate applied topically in human volunteers and in vitro skin diffusion cells using full-thickness skin and epidermal membranes. Results The present study showed that whilst significant levels of salicylate could be detected in the dermis and subcutaneous tissue of volunteers treated with the methylsalicylate formulation, negligible levels of salicylate were seen following application of the triethanolamine salicylate formulation. The tissue levels of salicylate from the methylsalicylate formulation were approx. 30-fold higher than the plasma concentrations. Conclusion The absorption and tissue concentration profiles for the commercial methylsalicylate formulation are indicative of direct tissue penetration and not solely redistribution by the systemic blood supply. PMID:9690946

  4. Topical glucocorticosteroids modulate the expression of CRABP I and II in human skin differently.

    PubMed

    Piletta, P; Jaconi, S; Siegenthaler, G; Didierjean, L; Saurat, J H

    1994-02-01

    Epidermal cells express two retinotic acid-binding proteins (CRABP I and II). Because CRABP II protein is strongly induced by topical retinoic acid, the respective roles of the two proteins in the pharmacological activity and toxicity of topical retinoids deserve particular attention. Since topical steroids diminish the irritation induced by retinoic acid (RA), whereas retinoic acid may counteract the atrophogenic effects of steroids, the possible interplay of both compounds in the expression of CRABP I and II appeared worth studying. We have analyzed the effects of topical application of triamcinolone acetonide (TA) on the retinoic acid-induced altered expression of CRABP I and II in normal human skin, at the protein and mRNA levels. We found that CRABP II protein and mRNA were strongly increased upon retinoic acid application: this induction was significantly inhibited by concomitant application of triamcinolone acetonide; a more potent steroid, difluocortolone valerate, was also found to diminish normal endogenous expression of CRABP II. In contrast, CRABP I protein was decreased by topical retinoic acid, and the down modulating effect of retinoic acid was counteracted by triamcinolone acetonide. PMID:8061932

  5. In vivo bioluminescence imaging to evaluate systemic and topical antibiotics against community-acquired methicillin-resistant Staphylococcus aureus-infected skin wounds in mice.

    PubMed

    Guo, Yi; Ramos, Romela Irene; Cho, John S; Donegan, Niles P; Cheung, Ambrose L; Miller, Lloyd S

    2013-02-01

    Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) frequently causes skin and soft tissue infections, including impetigo, cellulitis, folliculitis, and infected wounds and ulcers. Uncomplicated CA-MRSA skin infections are typically managed in an outpatient setting with oral and topical antibiotics and/or incision and drainage, whereas complicated skin infections often require hospitalization, intravenous antibiotics, and sometimes surgery. The aim of this study was to develop a mouse model of CA-MRSA wound infection to compare the efficacy of commonly used systemic and topical antibiotics. A bioluminescent USA300 CA-MRSA strain was inoculated into full-thickness scalpel wounds on the backs of mice and digital photography/image analysis and in vivo bioluminescence imaging were used to measure wound healing and the bacterial burden. Subcutaneous vancomycin, daptomycin, and linezolid similarly reduced the lesion sizes and bacterial burden. Oral linezolid, clindamycin, and doxycycline all decreased the lesion sizes and bacterial burden. Oral trimethoprim-sulfamethoxazole decreased the bacterial burden but did not decrease the lesion size. Topical mupirocin and retapamulin ointments both reduced the bacterial burden. However, the petrolatum vehicle ointment for retapamulin, but not the polyethylene glycol vehicle ointment for mupirocin, promoted wound healing and initially increased the bacterial burden. Finally, in type 2 diabetic mice, subcutaneous linezolid and daptomycin had the most rapid therapeutic effect compared with vancomycin. Taken together, this mouse model of CA-MRSA wound infection, which utilizes in vivo bioluminescence imaging to monitor the bacterial burden, represents an alternative method to evaluate the preclinical in vivo efficacy of systemic and topical antimicrobial agents.

  6. In vivo bioluminescence imaging to evaluate systemic and topical antibiotics against community-acquired methicillin-resistant Staphylococcus aureus-infected skin wounds in mice.

    PubMed

    Guo, Yi; Ramos, Romela Irene; Cho, John S; Donegan, Niles P; Cheung, Ambrose L; Miller, Lloyd S

    2013-02-01

    Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) frequently causes skin and soft tissue infections, including impetigo, cellulitis, folliculitis, and infected wounds and ulcers. Uncomplicated CA-MRSA skin infections are typically managed in an outpatient setting with oral and topical antibiotics and/or incision and drainage, whereas complicated skin infections often require hospitalization, intravenous antibiotics, and sometimes surgery. The aim of this study was to develop a mouse model of CA-MRSA wound infection to compare the efficacy of commonly used systemic and topical antibiotics. A bioluminescent USA300 CA-MRSA strain was inoculated into full-thickness scalpel wounds on the backs of mice and digital photography/image analysis and in vivo bioluminescence imaging were used to measure wound healing and the bacterial burden. Subcutaneous vancomycin, daptomycin, and linezolid similarly reduced the lesion sizes and bacterial burden. Oral linezolid, clindamycin, and doxycycline all decreased the lesion sizes and bacterial burden. Oral trimethoprim-sulfamethoxazole decreased the bacterial burden but did not decrease the lesion size. Topical mupirocin and retapamulin ointments both reduced the bacterial burden. However, the petrolatum vehicle ointment for retapamulin, but not the polyethylene glycol vehicle ointment for mupirocin, promoted wound healing and initially increased the bacterial burden. Finally, in type 2 diabetic mice, subcutaneous linezolid and daptomycin had the most rapid therapeutic effect compared with vancomycin. Taken together, this mouse model of CA-MRSA wound infection, which utilizes in vivo bioluminescence imaging to monitor the bacterial burden, represents an alternative method to evaluate the preclinical in vivo efficacy of systemic and topical antimicrobial agents. PMID:23208713

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

    PubMed Central

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

    2015-01-01

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

  8. Topical Delivery of siRNA into Skin using SPACE-peptide Carriers

    PubMed Central

    Chen, Ming; Zakrewsky, Michael; Gupta, Vivek; Anselmo, Aaron C.; Slee, Deborah H.; Muraski, John A.; Mitragotri, Samir

    2014-01-01

    Short-interfering RNAs (siRNAs) offer a potential tool for the treatment of skin disorders. However, applications of siRNA for dermatological conditions are limited by their poor permeation across the stratum corneum of the skin and low penetration into skin’s viable cells. In this study, we report the use of SPACE-peptide in combination with a DOTAP-based ethosomal carrier system to enhance skin delivery of siRNA. A DOTAP-based SPACE Ethosomal System significantly enhanced siRNA penetration into porcine skin in vitro by 6.3±1.7-fold (p<0.01) with an approximately 10-fold (p<0.01) increase in epidermis accumulation of siRNA compared to that from an aqueous solution. Penetration of siRNA was also enhanced at the cellular level. Internalization of SPACE-peptide occurred in a concentration dependent manner marked by a shift in intracellular distribution from punctate spots to diffused cytoplasmic staining at a peptide concentration of 10 mg/mL. In vitro delivery of GAPDH siRNA by SPACE peptide led to 83.3±3.0% knockdown relative to the control. In vivo experiments performed using female BALB/C mice also confirmed the efficacy of DOTAP-SES in delivering GAPDH-siRNA into skin. Topical application of DOTAP-SES on mice skin resulted in 63.2%±7.7% of GAPDH knockdown, which was significantly higher than that from GAPDH-siRNA PBS (p<0.05). DOTAP-SES formulation reported here may open new opportunities for cutaneous siRNA delivery. PMID:24434423

  9. Cytotoxicity testing of topical antimicrobial agents on human keratinocytes and fibroblasts for cultured skin grafts.

    PubMed

    Boyce, S T; Warden, G D; Holder, I A

    1995-01-01

    Cultured epidermal skin has become an adjunctive therapy for treatment of major burn injuries, but its effectiveness is greatly limited because of destruction by microbial contamination. To evaluate candidate antimicrobial agents for use with cultured skin, a combined cytotoxicity-antimicrobial assay system was developed for determination of toxicity to cultured human keratinocytes and fibroblasts and for determination of susceptibility or resistance of common burn wound organisms. Candidate agents including chlorhexidine gluconate, polymyxin B, mupirocin, sparfloxacin, or nitrofurazone were tested separately for inhibition of growth of human cells and for inhibitory activity to microorganisms with the wet disk assay. The data showed that (1) chlorhexidine gluconate (0.05%) was uniformly toxic to both cultured human cells and microorganisms; (2) nitrofurazone (0.02%) had dose-dependent toxicity to human cells and limited effectiveness against gram-negative microorganisms; (3) sparfloxacin (30 micrograms/ml) had low toxicity to human cells and retained antimicrobial activity against both gram-positive and gram-negative bacteria; (4) polymyxin B (400 U/ml) was not toxic to human cells and had intermediate effectiveness on gram-negative bacteria; and (5) mupirocin (48 micrograms/ml) had no toxicity to skin cells and had uniform effectiveness against Staphylococcus aureus including methicillin-resistant Staphylococcus aureus. Selection of topical antimicrobial drugs by these assays may improve effectiveness of cultured skin for burns and may be used to control other surgical wound infections.

  10. Cytotoxicity testing of topical antimicrobial agents on human keratinocytes and fibroblasts for cultured skin grafts.

    PubMed

    Boyce, S T; Warden, G D; Holder, I A

    1995-01-01

    Cultured epidermal skin has become an adjunctive therapy for treatment of major burn injuries, but its effectiveness is greatly limited because of destruction by microbial contamination. To evaluate candidate antimicrobial agents for use with cultured skin, a combined cytotoxicity-antimicrobial assay system was developed for determination of toxicity to cultured human keratinocytes and fibroblasts and for determination of susceptibility or resistance of common burn wound organisms. Candidate agents including chlorhexidine gluconate, polymyxin B, mupirocin, sparfloxacin, or nitrofurazone were tested separately for inhibition of growth of human cells and for inhibitory activity to microorganisms with the wet disk assay. The data showed that (1) chlorhexidine gluconate (0.05%) was uniformly toxic to both cultured human cells and microorganisms; (2) nitrofurazone (0.02%) had dose-dependent toxicity to human cells and limited effectiveness against gram-negative microorganisms; (3) sparfloxacin (30 micrograms/ml) had low toxicity to human cells and retained antimicrobial activity against both gram-positive and gram-negative bacteria; (4) polymyxin B (400 U/ml) was not toxic to human cells and had intermediate effectiveness on gram-negative bacteria; and (5) mupirocin (48 micrograms/ml) had no toxicity to skin cells and had uniform effectiveness against Staphylococcus aureus including methicillin-resistant Staphylococcus aureus. Selection of topical antimicrobial drugs by these assays may improve effectiveness of cultured skin for burns and may be used to control other surgical wound infections. PMID:7775517

  11. Photochemical model of photodynamic therapy applied to skin diseases by a topical photosensitizer

    NASA Astrophysics Data System (ADS)

    Fanjul-Vélez, F.; Salas-García, I.; Fernández-Fernández, L. A.; López-Escobar, M.; Buelta-Carrillo, L.; Ortega-Quijano, N.; Arce-Diego, J. L.

    2009-07-01

    Photodynamic Therapy (PDT) provides a non-invasive, efficient and safe treatment for skin diseases with good cosmetic results. These characteristics make this technique more advantageous than radiotherapy or chemotherapy, which present limitations in a big number of lesions, are painful in many cases and produce non-satisfactory cosmetic results. We present the clinical results obtained at present by this optical technique and a photochemical model of the PDT process applied to the skin by means of a topical photosensitizer, in order to find the optimal PDT parameters. Optical propagation inside the tissue is calculated by means of the three dimensional Beer-Lambert law, due to its facility to be integrated in the differential equations system used to model the photochemical processes involved. With this information it is possible to obtain an initial estimation about the optimal drug dose and the optical power required.

  12. Topical photodynamic therapy with 5-ALA in the treatment of arsenic-induced skin tumors

    NASA Astrophysics Data System (ADS)

    Karrer, Sigrid; Szeimies, Rolf-Markus; Landthaler, Michael

    1995-03-01

    A case of a 62-year-old woman suffering from psoriasis who was treated orally with arsenic 25 years ago is reported. The cumulative dose of arsenic trioxide was 800 mg. Since 10 years ago arsenic keratoses, basal cell carcinomas, Bowen's disease and invasive squamous cell carcinomas mainly on her hands and feet have developed, skin changes were clearly a sequence of arsenic therapy. Control of disease was poor, her right little finger had to be amputated. Topical photodynamic therapy with 5-aminolevulinic acid was performed on her right hand. Clinical and histological examinations 6 months after treatment showed an excellent cosmetic result with no signs of tumor residue.

  13. Inhibitory effects of [6]-gingerol on PMA-induced COX-2 expression and activation of NF-kappaB and p38 MAPK in mouse skin.

    PubMed

    Kim, Sue Ok; Chun, Kyung-Soo; Kundu, Joydeb Kumar; Surh, Young-Joon

    2004-01-01

    [6]-Gingerol, a major pungent ingredient of ginger (Zingiber officinale Roscoe, Zingiberaceae), has a wide array of pharmacologic effects. Previous studies have demonstrated that [6]-gingerol inhibits mouse skin tumor promotion and anchorage-independent growth of cultured mouse epidermal cells stimulated with epidermal growth factor. Cyclooxygenase-2 (COX-2), a key enzyme in the prostaglandin biosynthesis, has been recognized as a molecular target for many anti-inflammatory as well as chemopreventive agents. Topical application of [6]-gingerol inhibited phorbol 12-myristate 13-acetate -induced COX-2 expression. One of the essential transcription factors responsible for COX-2 induction is NF-kappaB. [6]-Gingerol suppressed NF-kappaB DNA binding activity in mouse skin. In addition, [6]-gingerol inhibited the phoshorylation of p38 mitogen-activated protein kinase which may account for its inactivation of NF-kappaB and suppression of COX-2 expression. PMID:15630166

  14. FTIR-ATR evaluation of topical skin protectants useful for sulfur mustard and related compounds

    NASA Astrophysics Data System (ADS)

    Braue, Ernest H., Jr.; Litchfield, Marty R.; Bangledorf, Catherine R.; Rieder, Robert G.

    1992-03-01

    The US Army has a need to develop topical protectants that can decrease the effects of cutaneous exposure to chemical warfare (CW) agents. Such materials would enhance a soldier's ability to carry out the mission in a chemically hostile environment, would lessen the burden on medical personnel, and may allow the casualties to return to duty in a shorter period of time than might otherwise be possible. In a preliminary report (E. H. Braue, Jr. and M. G. Pannella, Applied Spectrosc., 44, 1061 (1990)), we described a unique analytical method using FT-IR spectroscopy and the horizontal attenuated total reflectance (ATR) accessory for evaluating the effectiveness of topical skin protectants (TSPs) against penetration by chemical agents. We now describe the application of this method to the chemical warfare agent sulfur mustard (HD).

  15. Optical clearing assisted confocal microscopy of ex vivo transgenic mouse skin

    NASA Astrophysics Data System (ADS)

    Song, Eunjoo; Ahn, YoonJoon; Ahn, Jinhyo; Ahn, Soyeon; Kim, Changhwan; Choi, Sanghoon; Boutilier, Richard Martin; Lee, Yongjoong; Kim, Pilhan; Lee, Ho

    2015-10-01

    We examined the optical clearing assisted confocal microscopy of the transgenic mouse skin. The pinna and dorsal skin were imaged with a confocal microscope after the application of glycerol and FocusClear. In case of the glycerol-treated pinna, the clearing was minimal due to the inefficient permeability. However, the imaging depth was improved when the pinna was treated with FocusClear. In case of dorsal skin, we were able to image deeply to the subcutaneous connective tissue with both agents. Various skin structures such as the vessel, epithelium cells, cartilage, dermal cells, and hair follicles were clearly imaged.

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

    SciTech Connect

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

    1986-01-01

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

  17. Use of Topical Rapamycin in Facial Angiofibromas in Indian Skin Type

    PubMed Central

    Viswanath, Vishalakshi; Thakur, Parul; Pund, Poonam

    2016-01-01

    Introduction: Facial angiofibromas (FA) are the most visible cutaneous manifestations in patients with tuberous sclerosis (TS), often resulting in stigmatization of the affected individuals. Recent studies have suggested that topical rapamycin may be an effective treatment for angiofibromas. Aim: To study the safety and efficacy of topical rapamycin in treatment of FA in Type IV–VI skin type. Materials and Methods: Five female patients with FA were included in the study, four of whom had TS, whereas one had isolated angiofibromas without systemic involvement. The age of the patients varied from 6 to 44 years. After baseline evaluation, they were advised to apply topical rapamycin (0.1–1%) in white soft paraffin base twice daily. Follow-up varied from 1 month to 6 months and is ongoing. Results: A sustained improvement was observed with respect to erythema, size as well as extent of the lesions as early as within 2 weeks of starting treatment. No side effects were observed. A correlation between duration of angiofibromas and effectiveness of treatment was noted. Conclusion: Topical rapamycin appears to be a safe and effective alternative to surgical or laser-based treatments in patients with FA. This treatment shows potential to be a first-line management for FA and appears safe to start in early childhood. PMID:26951710

  18. In vivo evaluation of the penetration of topically applied drugs into human skin by spectroscopic methods.

    PubMed

    Sennhenn, B; Giese, K; Plamann, K; Harendt, N; Kölmel, K

    1993-01-01

    Spectroscopic techniques are reported on which allow to study in vivo the penetration behaviour of topically applied light-absorbing drugs into human skin. Remittance spectroscopy, a purely optical method, provides a good tool in both, skin adaptation by use of a remote viewing head coupled to the spectrometer via optical fibres, and adequate sensitivity for the detection of small amounts of the applied drugs. The measuring depth in the skin is determined by the wavelength-dependent optical penetration depth, which itself depends on light absorption and light scattering. In the UV-spectral region the optical penetration depth is of the order of the thickness of the stratum corneum (UV-A) or of only a superficial part of it (UV-B, UV-C). Fluorescence spectroscopy, another optical method, offers two kinds of drug detection, a direct one in case of self-fluorescent drugs or an indirect one being based on the light absorption of the drug, which may give rise to a screening of the self-fluorescence of the skin itself or of an applied marker. The measuring depth is comparable to that achieved with remittance spectroscopy. A third method is photothermal spectroscopy which is determined by thermal properties of the skin in addition to optical properties. Photothermal spectroscopy is unique in that it allows depth profiles of drug concentration to be measured non-invasively, as the photothermal measuring depth can be changed by varying the modulation frequency of the intensity-modulated incident light. Results of measurements demonstrating the potentials of these spectroscopic methods are presented.

  19. Efficacy of topically applied tocopherols and tocotrienols in protection of murine skin from oxidative damage induced by UV-irradiation.

    PubMed

    Weber, C; Podda, M; Rallis, M; Thiele, J J; Traber, M G; Packer, L

    1997-01-01

    To assess the efficacy of various forms of vitamin E in protection of skin from UV-light-induced oxidative stress, vitamin E (tocotrienol-rich fraction of palm oil, TRF) was applied to mouse skin and the contents of antioxidants before and after exposure to UV-light were measured. Four polypropylene plastic rings (1 cm2) were glued onto the animals' backs, and 20 microliters 5% TRF in polyethylene glycol-400 (PEG) was applied to the skin circumscribed by two rings and 20 microliters PEG to the other two rings. After 2 h, the skin was washed and half of the sites were exposed to UV-irradiation (2.8 mW/cm2 for 29 mi: 3 MED). TRF treatment (n = 19 mice) increased mouse skin alpha-tocopherol 28 +/- 16-fold, alpha-tocotrienol 80 +/- 50-fold, gamma-tocopherol 130 +/- 108-fold, and gamma-tocotrienol 51 +/- 36-fold. A significantly higher percentage of alpha-tocopherol was present in the skin as compared with that in the applied TRF. After UV-irradiation, all vitamin E forms decreased significantly (p < .01), while a larger proportion of the vitamin E remained in PEG-treated (approximately 80%) compared with TRF-treated (approximately 40%) skin. Nonetheless, vitamin E concentrations in irradiated TRF-treated skin were significantly higher than in the nonirradiated PEG-treated (control) skin (p < .01). Thus, UV-irradiation of skin destroys its antioxidants: however, prior application of TRF to mouse skin results in preservation of vitamin E.

  20. Effects of Topical Emu Oil on Burn Wounds in the Skin of Balb/c Mice

    PubMed Central

    Afshar, Mohammad; Ghaderi, Reza; Zardast, Mahmoud; Delshad, Parvin

    2016-01-01

    The goal of this study was to determine the effect of topical Emu oil on the healing of burn wounds and hair follicle restoration in superficial II-degree burns in the skin of Balb/c mice. Thirty-two male Balb/c mice with burns on the back of the neck were divided into two groups: The Emu oil group received topical Emu oil twice daily, whereas the control was left untreated. Skin biopsies were obtained on days 4, 7, 10, and 14 of the experiment. Then the specimens were viewed with Olympus SZX research microscope. The Emu oil treated burns were found to heal more slowly and inflammation lasted longer in this group. The number of hair follicles in the margins of the wounds increased through time in the Emu oil group compared to the control group. Also, the hair follicles in the Emu oil group were in several layers and seemed to be more active and mature. Moreover, Emu oil had a positive effect on fibrogenesis and synthesis of collagen. The findings indicate that although Emu oil delays the healing process, it has a positive effect on wound healing and it increases the number of hair follicles in the margins of the wound. PMID:27069472

  1. In vivo measurement of human skin absorption of topically applied substances by a photoacoustic technique.

    PubMed

    Gutiérrez-Juárez, G; Vargas-Luna, M; Córdova, T; Varela, J B; Bernal-Alvarado, J J; Sosa, M

    2002-08-01

    A photoacoustic technique is used for studying topically applied substance absorption in human skin. The proposed method utilizes a double-chamber PA cell. The absorption determination was obtained through the measurement of the thermal effusivity of the binary system substance-skin. The theoretical model assumes that the effective thermal effusivity of the binary system corresponds to that of a two-phase system. Experimental applications of the method employed different substances of topical application in different parts of the body of a volunteer. The method is demonstrated to be an easily used non-invasive technique for dermatology research. The relative concentrations as a function of time of substances such as ketoconazol and sunscreen were determined by fitting a sigmoidal function to the data, while an exponential function corresponds to the best fit for the set of data for nitrofurazona, vaseline and vaporub. The time constants associated with the rates of absorption, were found to vary in the range between 10 and 58 min, depending on the substance and the part of the body. PMID:12214760

  2. Pharmacokinetics of ketoprofen in rabbit skin following topical application of lipid nanoparticles

    NASA Astrophysics Data System (ADS)

    Patel, Umesh

    The purpose of the thesis was to quantify ketoprofen (KTP) in rabbit skin following the topical application of lipid nanoparticles (Nanostructured lipid carriers, NLC). We tested two different types of formulations: one is (G') in which KTP is incorporated within the nanostructured lipid carriers (NLC) and the other is (H') which is a mixture of the nanostructured lipid carriers (NLC) and KTP dissolved in a vehicle (10% glycerol + 1% xanthan gum). Ketoprofen (KTP) is a non-steroidal anti-inflammatory drug administered systemically to treat arthritis. By conventional route severe side effects at the gastrointestinal level have been observed. Topical-application of lipid nanoparticles would be convenient alternative. The project is based on the (1) To study the calibration of microdialysis probes in both environment, in vivo as well as in vitro; (2) To compare two different type of formulation one is (G') with KTP incorporated within the nanostructured lipid carriers (NLC) and the other is (H') a mixture of the nanostructured lipid carriers (NLC) and KTP dissolved in a the vehicle (10% glycerol + 1% xanthan gum). The results of this study show a clear difference between the skin concentration profiles of the two formulations. Time to reach the maximum concentration is similar for both formulations. The formulation H', containing KTP is in external phase had higher Cmax (334ng/ml) than formulation G' containing KTP inside lipid particles (Cmax 32ng/ml).

  3. Phase I study of a topical skin protectant against chemical warfare agents.

    PubMed

    Eisenkraft, Arik; Krivoy, Amir; Vidan, Aviv; Robenshtok, Eyal; Hourvitz, Ariel; Dushnitsky, Tsvika; Markel, Gal

    2009-01-01

    Vesicants and some nerve agents penetrate exposed skin, mainly through the sensitive integration areas of the personal protective equipment. Therefore, improving dermal barrier with a topical agent should reduce the threat of exposure. A topical skin protectant lotion (IB1) was developed to improve protection against chemical warfare agents. Preclinical studies in several animal models have proven the protective efficacy of IB1. Here we present the results of a randomized placebo-controlled, double-blind phase I clinical study, performed with 34 healthy volunteers. The study tested the safety of repeated applications, including ruling out transdermal permeation of magnesium, which may lead to a dangerous blood magnesium level, since the lotion contains magnesium sulfate. Other objectives included detection of dermatological adverse effects, assessment of application convenience, and effect on daily activities. Importantly, no serious adverse effects were recorded and the lotion did not interfere with daily tasks. There were no significant differences in magnesium levels between the placebo and the study groups in any of the applications. No toxic levels of magnesium were found in either group. We conclude that IB1 is probably safe, easily self-applied, and does not cause any significant inconvenience. Therefore, IB1 can be considered as an adjunctive chemical, biological, and radio-nuclear (CBRN) protective aid to field soldiers.

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

    PubMed

    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.

  5. Ultraviolet radiation, aging and the skin: prevention of damage by topical cAMP manipulation

    PubMed Central

    Amaro-Ortiz, Alexandra; Yan, Betty; D’Orazio, John A.

    2015-01-01

    Being the largest and most visible organ of the body and heavily influenced by environmental factors, skin is ideal to study long-term effects of aging. Throughout our lifetime, we accumulate damage generated by UV radiation. UV causes inflammation, immune changes, physical changes, impaired wound healing and DNA damage that promotes cellular senescence and carcinogenesis. Melanoma is the deadliest form of skin cancer and among the malignancies of highest increasing incidence over the last several decades. Melanoma incidence is directly related to age, with highest rates in individuals over the age of 55 years, making it a clear age-related disease. In this review, we will focus on UV-induced carcinogenesis and photo aging along with natural protective mechanisms that reduce amount of “realized” solar radiation dose and UV-induced injury. We will focus on the theoretical use of forskolin, a plant-derived pharmacologically active compound to protect the skin against UV injury and prevent aging symptoms by up-regulating melanin production. We will discuss its use as a topically-applied root-derived formulation of the Plectranthus barbatus (Coleus forskolii) plant that grows naturally in Asia and that has long been used in various Aryuvedic teas and therapeutic preparations. PMID:24838074

  6. Ethosomes-based topical delivery system of antihistaminic drug for treatment of skin allergies.

    PubMed

    Goindi, Shishu; Dhatt, Bhavnita; Kaur, Amanpreet

    2014-01-01

    Cetirizine is indicated for the treatment of allergic conditions such as insect bites and stings, atopic and contact dermatitis, eczema, urticaria. This investigation deals with development of a novel ethosome-based topical formulation of cetirizine dihydrochloride for effective delivery. The optimised formulation consisting of drug, phospholipon 90 G™ and ethanol was characterised for drug content, entrapment efficiency, pH, vesicular size, spreadability and rheological behaviour. The ex vivo permeation studies through mice skin showed highest permeation flux (16.300 ± 0.300 µg/h/cm(2)) and skin retention (20.686 ± 0.517 µg/cm(2)) for cetirizine-loaded ethosomal vesicles as compared to conventional formulations. The in vivo pharmacodynamic evaluation of optimised formulation was assessed against oxazolone-induced atopic dermatitis (AD) in mice. The parameters evaluated were reduction in scratching score, erythema score, skin hyperplasia and dermal eosinophil count. Our results suggest that ethosomes are effective carriers for dermal delivery of antihistaminic drug, cetirizine, for the treatment of AD. PMID:24963956

  7. Ethosomes-based topical delivery system of antihistaminic drug for treatment of skin allergies.

    PubMed

    Goindi, Shishu; Dhatt, Bhavnita; Kaur, Amanpreet

    2014-01-01

    Cetirizine is indicated for the treatment of allergic conditions such as insect bites and stings, atopic and contact dermatitis, eczema, urticaria. This investigation deals with development of a novel ethosome-based topical formulation of cetirizine dihydrochloride for effective delivery. The optimised formulation consisting of drug, phospholipon 90 G™ and ethanol was characterised for drug content, entrapment efficiency, pH, vesicular size, spreadability and rheological behaviour. The ex vivo permeation studies through mice skin showed highest permeation flux (16.300 ± 0.300 µg/h/cm(2)) and skin retention (20.686 ± 0.517 µg/cm(2)) for cetirizine-loaded ethosomal vesicles as compared to conventional formulations. The in vivo pharmacodynamic evaluation of optimised formulation was assessed against oxazolone-induced atopic dermatitis (AD) in mice. The parameters evaluated were reduction in scratching score, erythema score, skin hyperplasia and dermal eosinophil count. Our results suggest that ethosomes are effective carriers for dermal delivery of antihistaminic drug, cetirizine, for the treatment of AD.

  8. Sunscreens: topical and systemic approaches for protection of human skin against harmful effects of solar radiation

    SciTech Connect

    Pathak, M.A.

    1982-09-01

    This review deals with topical and systemic approaches for protection of human skin against the harmful effects of solar radiation. Two concerns about the deleterious effects of sun exposure involve: (1) acute effects (e.g., sunburn and drug-induced phototoxicity) and (2) potential long-term risks of repeated sun exposures leading to development of solar elastosis, keratoses, induction of both nonmelanoma and melanoma skin cancer, and alteration of immune responses and functions. Action spectra of normal and abnormal reactions of human skin to acute and chronic effects of solar radiation are presented with a view to helping the physician prescribe the appropriate sunscreens. Factors that influence acute effects of sunburn are reviewed. Various artificial methods effective in minimizing or preventing harmful effects of solar radiation, both in normal individuals and in patients with photosensitivity-related problems, are discussed. Emphasis is placed on the commercially available chemical sunscreens and their properties. Sun protection factor (SPF) values of several brand-name formulations determined with a solar simulator under indoor conditions (laboratory) and with solar radiation under natural, field conditions are presented. Factors responsible for variations of SPF values observed under indoor and outdoor conditions are reviewed. Systemic photoprotective agents and their limitations are outlined. The photobiology of melanin pigmentation (the tanning reaction) is briefly discussed, with emphasis on the dangers of using quick-tanning lotions for stimulation of the tanning reaction.

  9. Comparison of skin permeability for three diclofenac topical formulations: an in vitro study.

    PubMed

    Folzer, E; Gonzalez, D; Singh, R; Derendorf, H

    2014-01-01

    Diclofenac is a hydrophilic non-steroidal anti-inflammatory drug (NSAID) widely used in humans and animals. There are limited published studies evaluating diclofenac's skin permeation following topical administration. The aim of our study was to evaluate and compare the in vitro permeation of three different diclofenac-containing formulations (patch, gel, solution) over 24 hours. These formulations were applied (n = 6 per formulation) to pig skin sandwiched between the two chambers in a static Franz diffusion cell and aliquots from the receptor medium were sampled at pre-defined time points. An HPLC method with UV detection was developed and validated with the aim of characterizing the transepidermal penetration in the in vitro system. Using this assay to determine the permeation parameters, results at 24 hours showed that the Flector patch released the highest drug amount (54.6%), whereas a lower drug amount was delivered with the Voltaren Emulgel (38.2%) and the solution (34.4%). The commercial gel showed the highest flux (39.9 +/- 0.9 microg/cm2/h) and the shortest lag-time (1.97 +/- 0.02 h). Based on these in vitro results using pig skin, the transdermal patch resulted in a long-lasting controlled release of diclofenac, while the gel had the shortest lag-time.

  10. Atopic dermatitis: studies of skin permeability and effectiveness of topical PUVA treatment.

    PubMed

    Ogawa, H; Yoshiike, T

    1992-12-01

    Ultraviolet light is effective treatment for patients with atopic dermatitis that is resistant to conservative therapy, or complicated by adverse effects of extended steroid use. We designed a protocol using topical psoralen chemotherapy with ultraviolet A (PUVA) to treat atopic dermatitis in 114 patients. Clinical results were excellent, with complete clearing in 50% of patients receiving daily treatment. Histologic and immunologic values correlated with the clinical response, including reduced epidermal thickness, and decreased numbers of epidermal Langerhans cells and dermal mast and mononuclear cell infiltrates. The pattern of keratin 14-positive keratinocytes returned toward normal. In addition, the water-holding capacity of the stratum corneum increased to near normal levels. We also studied stratum corneum permeability in lesional and nonlesional skin using the dimethyl sulfoxide whealing test and theophylline absorption studies. Compared with controls, permeability was markedly increased in lesional skin and mildly increased in nonlesional skin in patients with atopic dermatitis. These results suggest that immune abnormalities and barrier dysfunction participate in the pathogenesis of atopic dermatitis.

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

    SciTech Connect

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

    2013-10-15

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

  12. JAK3 as an Emerging Target for Topical Treatment of Inflammatory Skin Diseases

    PubMed Central

    Alves de Medeiros, Ana Karina; Speeckaert, Reinhart; Desmet, Eline; Van Gele, Mireille; De Schepper, Sofie; Lambert, Jo

    2016-01-01

    The recent interest and elucidation of the JAK/STAT signaling pathway created new targets for the treatment of inflammatory skin diseases (ISDs). JAK inhibitors in oral and topical formulations have shown beneficial results in psoriasis and alopecia areata. Patients suffering from other ISDs might also benefit from JAK inhibition. Given the development of specific JAK inhibitors, the expression patterns of JAKs in different ISDs needs to be clarified. We aimed to analyze the expression of JAK/STAT family members in a set of prevalent ISDs: psoriasis, lichen planus (LP), cutaneous lupus erythematosus (CLE), atopic dermatitis (AD), pyoderma gangrenosum (PG) and alopecia areata (AA) versus healthy controls for (p)JAK1, (p)JAK2, (p)JAK3, (p)TYK2, pSTAT1, pSTAT2 and pSTAT3. The epidermis carried in all ISDs, except for CLE, a strong JAK3 signature. The dermal infiltrate showed a more diverse expression pattern. JAK1, JAK2 and JAK3 were significantly overexpressed in PG and AD suggesting the need for pan-JAK inhibitors. In contrast, psoriasis and LP showed only JAK1 and JAK3 upregulation, while AA and CLE were characterized by a single dermal JAK signal (pJAK3 and pJAK1, respectively). This indicates that the latter diseases may benefit from more targeted JAK inhibitors. Our in vitro keratinocyte psoriasis model displayed reversal of the psoriatic JAK profile following tofacitinib treatment. This direct interaction with keratinocytes may decrease the need for deep skin penetration of topical JAK inhibitors in order to exert its effects on dermal immune cells. In conclusion, these results point to the important contribution of the JAK/STAT pathway in several ISDs. Considering the epidermal JAK3 expression levels, great interest should go to the investigation of topical JAK3 inhibitors as therapeutic option of ISDs. PMID:27711196

  13. Topical Skin Cancer Therapy Using Doxorubicin-Loaded Cationic Lipid Nanoparticles and lontophoresis.

    PubMed

    Huber, Lucas A; Pereira, Tatiana A; Ramos, Danielle N; Rezende, Lucas C D; Emery, Flávio S; Sobral, Lays Martin; Leopoldino, Andréia Machado; Lopez, Renata F V

    2015-11-01

    The topical administration of chemotherapeutics is a promising approach for the treatment of skin cancer; however, different pharmaceutical strategies are required to allow large amounts of drug to penetrate tumors. This work examined the potential of the anodic iontophoresis of doxorubicin-loaded cationic solid lipid nanoparticles (DOX-SLN) to increase the distribution and tumor penetration of DOX. A double-labeled cationic DOX-SLN composed of the lipids stearic acid and monoolein and a new BODIPY dye was prepared and characterized. The skin distribution and penetration of DOX were evaluated in vitro using confocal microscopy and vertical diffusion cells, respectively. The antitumor potential was evaluated in vivo through the anodic iontophoresis of DOX-SLN in squamous cell carcinoma induced in nude BALB/c mice. The encapsulation of DOX drastically altered the DOX partition coefficient and increased the distribution of DOX in the lipid matrix of the stratum corneum (SC). The association with iontophoresis created high-concentration drug reservoir zones in the follicles of the skin. Although the iontophoresis of a DOX solution increased the penetration of DOX in the viable epidermis by approximately 4-fold, the iontophoresis of cationic DOX-SLN increased the DOX penetration by approximately 50-fold. In vivo, the DOX-SLN iontophoretic treatment was effective in inhibiting tumor cell survival and tumor growth and was accompanied by an increase in keratinization and consequent cell death. These results indicate a strong and synergic effect of iontophoresis with DOX-SLN and provide a potential strategy for the treatment of skin cancer.

  14. Inhibition of tumour promotion in mouse skin by extracts of rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia), unique South African herbal teas.

    PubMed

    Marnewick, Jeanine; Joubert, Elizabeth; Joseph, Shamiel; Swanevelder, Sonja; Swart, Pieter; Gelderblom, Wentzel

    2005-06-28

    The modulating effect of ethanol/acetone (E/A) soluble fractions, prepared from methanolic extracts of processed and unprocessed rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia) as well as green (Camellia sinensis) teas was established in a two-stage mouse skin carcinogenesis assay. Topical application of the tea fractions prior to the tumour promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), on ICR mouse skin initiated with 7,12-dimethylbenz[a]anthracene (DMBA) suppressed skin tumorigenesis significantly (P<0.001) with the green tea E/A fraction exhibiting a 100% inhibition, unprocessed honeybush 90%, processed honeybush 84.2%, processed rooibos 75% and unprocessed rooibos 60%. The green tea fraction, with the highest flavanol/proanthocyanidin content, also exhibited the highest protective activity (99%) against hepatic microsomal lipid peroxidation, and completely inhibited skin tumour formation. Differences in the flavanol/proanthocyanidin and flavonol/flavone composition and/or non polyphenolic constituents are likely to be important determinants in the inhibition of tumour promotion by the herbal tea E/A fractions in mouse skin.

  15. 2,6-Dithiopurine, a nucleophilic scavenger, protects against mutagenesis in mouse skin treated in vivo with 2-(chloroethyl) ethyl sulfide, a mustard gas analog

    SciTech Connect

    Boulware, Stephen; Fields, Tammy; McIvor, Elizabeth; Powell, K. Leslie; Abel, Erika L.; Vasquez, Karen M.; MacLeod, Michael C.

    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.

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

    PubMed

    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.

  17. Inhibition of UVB induced DNA photodamage in mouse epidermis by topically applied alpha-tocopherol.

    PubMed

    McVean, M; Liebler, D C

    1997-08-01

    Ultraviolet B (UVB, 290-320 nm) exposure results in a variety of cellular insults including induction of cyclobutane pyrimidine dimers in DNA. Accumulation of these lesions can lead to mutations in critical genes and contribute to the development of nonmelanoma skin cancer. Topically applied alpha-tocopherol (vitamin E) has previously been shown to prevent the induction of skin tumors in UVB irradiated female C3H/HeNTac mice. We hypothesized that alpha-tocopherol, which absorbs strongly in the UVB, may act as a sunscreen to prevent photodamage. To explore possible mechanisms of photoprotection, we topically applied alpha-tocopherol dispersed in a neutral cream vehicle to the dorsal epidermis of female C3H/HeNTac mice and exposed them to 2.5 J/m2/s of UVB for 60 min. Immediately after exposure, we analyzed thymine dimer levels in DNA by capillary gas chromatography with electron capture detection. Epidermal DNA from mice receiving this UVB dose contained 247 +/- 42 pmol thymine dimers/micromol thymine. Topical application of alpha-tocopherol inhibited dimer formation in a dose-dependent manner. A 1% alpha-tocopherol dispersion inhibited the formation of thymine dimers to 43% of levels in vehicle controls. Several vitamin E compounds, including alpha-tocopherol acetate, alpha-tocopherol methyl ether, gamma-tocopherol, and delta-tocopherol also inhibited thymine dimer formation, but were five- to ten-fold less potent than alpha-tocopherol. A variety of commercially available sunscreens were also less potent than alpha-tocopherol in their ability to reduce dimer formation. These results suggest that DNA photoprotection is an important mechanism by which topically applied alpha-tocopherol can inhibit UVB induced skin cancer. Alpha-Tocopherol acetate, the most common form of vitamin E in commercial skin care products, conferred less protection, perhaps due to its lower absorptivity in the UVB. Our results further underscore the importance of determining which forms of

  18. Immunosuppressive macrolides of the type FK 506: a novel class of topical agents for treatment of skin diseases?

    PubMed

    Meingassner, J G; Stütz, A

    1992-06-01

    The immunosuppressive macrolide antibiotics FK 506 and rapamycin were tested for topical activity in experimental allergic contact dermatitis of farm pigs. This species was used because pig skin, in comparison to rodent skin, resembles human skin more closely. For comparison, cyclosporine A (CyA), which is orally but not topically active in patients with skin disease, dexamethasone, and clobetasol propionate were used. Treatment was performed twice, 30 min and 6 h after elicitation of challenge reaction. Topical application of 0.4 to 0.04% FK 506 caused a pronounced inhibition of inflammatory skin reactions of hypersensitivity to dinitrofluorobenzene. The treatment response was similar to the activity of 0.13% clobetasole. Dexamethasone (1.2%) was less active than clobetasol. In contrast, rapamycin and CyA were inactive at concentrations of 1.2 and 10%, respectively. Because the pig data on corticosteroids and cyclosporine A are in agreement with clinical findings, these studies indicate that immunosuppressive macrolides of the type FK 506 may be useful drugs for the topical treatment of human skin diseases that respond to local corticosteroids and oral treatment with cyclosporine A.

  19. Skin Concentrations of Topically Applied Substances in Reconstructed Human Epidermis (RHE) Compared with Human Skin Using in vivo Confocal Raman Microscopy.

    PubMed

    Fleischli, Franziska D; Morf, Fabienne; Adlhart, Christian

    2015-01-01

    Detailed knowledge about the skin concentration of topically applied substances is important to understand their local pharmacological activity. In particular since in vitro models of reconstructed human epidermis are increasingly used as models for diseased skin. In general, diffusion cell experiments are performed to determine the diffusion flux of test substances through either skin models or excised skin both from humans and animals. Local concentrations of the test substances within the skin are then calculated applying diffusion laws and suitable boundary conditions. In this study we used a direct approach to reveal the local concentrations of test substances within skin using confocal Raman microscopy. This non-invasive method can also be applied in vivo and therefore we directly compared in vivo concentrations with those obtained from commercially available reconstructed human epidermis (RHE). Hydrophilic and lipophilic test substances with log Pow from -0.07 to 5.91 were topically applied on human skin in vivo and RHE from SkinEthic was used as the commercial skin model. Local concentration profiles in the stratum corneum (SC) showed substantial differences between the RHE model and the in vivo situation. Differences between RHE models and human skin in vivo were also observed in their molecular composition, in particular in terms of their water profile, lipid content and the presence of natural moisturizing factor (NMF). Confocal Raman is shown to be a powerful non-invasive method for qualitative and quantitative comparative studies between RHE models and human skin in vivo. This method can also be applied to validate RHE models for future use in clinical studies. PMID:26507219

  20. Reduction of sunburn damage to skin by topical application of vitamin E acetate following exposure to ultraviolet B radiation: effect of delaying application or of reducing concentration of vitamin E acetate applied.

    PubMed

    Trevithick, J R; Shum, D T; Redae, S; Mitton, K P; Norley, C; Karlik, S J; Groom, A C; Schmidt, E E

    1993-12-01

    The skin of the skh-1 mouse after ultraviolet B (280-320 nm, UVB) irradiation shows the pathological changes typical of sunburn damage: spongiosis (edematous spaces) around some cells, necrosis of keratinocytes, giving rise to sunburn cells, inflammatory infiltration of polymorphonuclear leucocytes, etc. In our previous study, these were accompanied by erythema, increased skin sensitivity, and edematous swelling. The topical application of tocopherol acetate (TA) immediately after the UVB exposure decreased these changes. In this paper, multiple measurements of the skin thickness were made at different locations along the magnetic resonance imaging (MRI) cross-sectional image of the skin. This permits effects to be quantified with (if desired) the contralateral half of the back serving as an internal control, either exposed (positive control) or unexposed (negative control). Topical application of TA resulted in an increase in the concentration of free tocopherol in the skin. No qualitative differences in ultrastructural appearance of the UVB-irradiated, TA-treated skin could be discerned by careful examination. In vivo high resolution video microscopy of blood flow in venules of the irradiated mouse ear revealed a large (tenfold) but not statistically significant decrease in stationary lymphocytes adhering to the venule walls. The delaying of the application of TA up to 8 hours after the termination of UVB irradiation still offered statistically significant protection as did immediate application of 5% TA in diluent Myritol 318 (Delios S, Henkel).

  1. Assessment of Topical Skin Care Practices in Long-Term Institutional Nursing Care from a Health Service Perspective.

    PubMed

    Rahn, Yasmin; Lahmann, Nils; Blume-Peytavi, Ulrike; Kottner, Jan

    2016-06-01

    Skin aging is associated with increased skin vulnerability and susceptibility to ulcerations and dermatoses, making intensive skin care required, especially for older adults. As part of a nationwide prevalence study, data of 3,385 residents 60 and older were collected to analyze skin care practices in German long-term care facilities. The objective of the current study was to gain detailed insights into frequencies of leave-on skin care product applications by nursing care professionals for older adults. The 10 most frequently treated body parts accounted for >94% of all skin applications. Variations related to gender, age, and skin areas indicate differences in perceived skin care needs, although the evidence base supporting basic skin care interventions in this setting is weak. Gender, age, and clinical status seem to influence skin care practices. These factors must be taken into account to improve topical skin care and health in long-term care. [Journal of Gerontological Nursing, 42(6), 18-24.].

  2. Effects of topical petrolatum and salicylic acid upon skin photoreaction to UVA.

    PubMed

    Birgin, Bahar; Fetil, Emel; Ilknur, Turna; Tahsin Güneş, Ali; Ozkan, Sebnem

    2005-01-01

    Various agents which can be used in combination can also interfere with phototherapy. In this study, the effects of topical petrolatum and 20% salicylic acid in petrolatum upon skin photoreaction to UVA were investigated, in an in vivo test. Minimal phototoxic dose (MPD) test was performed on 31 volunteers and the test was repeated with thin (0.1 cc/25 cm(2)) petrolatum, thick (0.3 cc/25 cm(2)) petrolatum, thin 20% salicylic acid in petrolatum, thick 20% salicylic acid in petrolatum and sunscreen. The effect of each agent on MPD was investigated. MPD was increased with thin and thick applications of all agents. Also, MPD was increased with 20% salicylic acid in petrolatum when compared with pure petrolatum, in the same thickness. The application of petrolatum and salicylic acid in petrolatum just before PUVA therapy is not recommended because of their blocking effects.

  3. Feasibility of measuring the bioavailability of topical betamethasone dipropionate in commercial formulations using drug content in skin and a skin blanching bioassay.

    PubMed

    Pershing, L K; Silver, B S; Krueger, G G; Shah, V P; Skelley, J P

    1992-01-01

    An in vivo technique has been developed which simultaneously compares a skin blanching bioassay with drug content in human stratum corneum following topical application of four 0.05% betamethasone dipropionate formulations. Bioavailability of drug from commercial cream and ointment formulations was assessed by quantification of drug content in tape-stripped stratum corneum and skin blanching in the treated skin site under occluded conditions. Tape-stripping removed stratum corneum to a varying degree between individuals but was consistent (35%) within an individual with all formulations, day to day. A correlation (r = 0.9935) between the amount of drug in the treated stratum corneum normalized for surface area and the corresponding skin blanching score was observed with four 0.05% betamethasone dipropionate formulations. Increasing the amount of drug in the tape-stripped stratum corneum correlated with an increased skin blanching score. Ointment formulations delivered more drug to the skin and produced greater blanching scores than the cream formulations. Topical corticosteroid content in the treated skin site can therefore be quantified and correlates well with the resulting pharmacodynamic activity.

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

    PubMed

    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

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

    PubMed

    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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

    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.

  8. Which skin model is the most appropriate for the investigation of topically applied substances into the hair follicles?

    PubMed

    Lademann, J; Richter, H; Meinke, M; Sterry, W; Patzelt, A

    2010-01-01

    It has recently been demonstrated by the utilization of different techniques, such as differential stripping and laser scanning microscopy, that the hair follicles represent an efficient long-term reservoir for topically applied substances. In the present paper, the different in vivo techniques are compared to those of in vitro analysis. It was found that in vitro measurements on pig ear skin are highly superior for the analysis of follicular penetration, as compared to in vitro investigations on excised human skin, mainly due to the fact that the human skin contracts after removal. Restretching of the skin to its original size mainly stretches the interfollicular fibres, whereas the fibres around the hair follicles remain contracted. In contrast to excised human skin, pig ear tissue does not contract when the cartilage is not removed. Moreover, it has an intact barrier on both sides of the ear. Regardless of the fact that the hair follicles on pig ear skin are larger than those of humans, the porcine ear skin represents a more suitable in vitro model for the analysis of the penetration and storage of topically applied substances in the hair follicles than excised human skin. PMID:20090408

  9. Chronic ultraviolet exposure-induced p53 gene alterations in sencar mouse skin carcinogenesis model

    SciTech Connect

    Tong, Ying; Smith, M.A.; Tucker, S.B.

    1997-06-27

    Alterations of the tumor suppressor gene p53 have been found in ultraviolet radiation (UVR) related human skin cancers and in UVR-induced murine skin tumors. However, links between p53 gene alterations and the stages of carcinogenesis induced by UVR have not been clearly defined. We established a chronic UVR exposure-induced Sencar mouse skin carcinogenesis model to determine the frequency of p53 gene alterations in different stages of carcinogenesis, including UV-exposed skin, papillomas, squamous-cell carcinomas (SCCs), and malignant spindle-cell tumors (SCTs). A high incidence of SCCs and SCTs were found in this model. Positive p53 nuclear staining was found in 10137 (27%) of SCCs and 12124 (50%) of SCTs, but was not detected in normal skin or papillomas. DNA was isolated from 40 paraffin-embedded normal skin, UV-exposed skin, and tumor sections. The p53 gene (exons 5 and 6) was amplified from the sections by using nested polymerase chain reaction (PCR). Subsequent single-strand conformation polymorphism (SSCP) assay and sequencing analysis revealed one point mutation in exon 6 (coden 193, C {r_arrow} A transition) from a UV-exposed skin sample, and seven point mutations in exon 5 (codens 146, 158, 150, 165, and 161, three C {r_arrow} T, two C {r_arrow} A, one C {r_arrow} G, and one A {r_arrow} T transition, respectively) from four SCTs, two SCCs and one UV-exposed skin sample. These experimental results demonstrate that alterations in the p53 gene are frequent events in chronic UV exposure-induced SCCs and later stage SCTs in Sencar mouse skin. 40 refs., 5 figs., 1 tab.

  10. Ex vivo Culture of Mouse Embryonic Skin and Live-imaging of Melanoblast Migration

    PubMed Central

    Mort, Richard L.; Keighren, Margaret; Hay, Leonard; Jackson, Ian J.

    2014-01-01

    Melanoblasts are the neural crest derived precursors of melanocytes; the cells responsible for producing the pigment in skin and hair. Melanoblasts migrate through the epidermis of the embryo where they subsequently colonize the developing hair follicles1,2. Neural crest cell migration is extensively studied in vitro but in vivo methods are still not well developed, especially in mammalian systems. One alternative is to use ex vivo organotypic culture3-6. Culture of mouse embryonic skin requires the maintenance of an air-liquid interface (ALI) across the surface of the tissue3,6. High resolution live-imaging of mouse embryonic skin has been hampered by the lack of a good method that not only maintains this ALI but also allows the culture to be inverted and therefore compatible with short working distance objective lenses and most confocal microscopes. This article describes recent improvements to a method that uses a gas permeable membrane to overcome these problems and allow high-resolution confocal imaging of embryonic skin in ex vivo culture6. By using a melanoblast specific Cre-recombinase expressing mouse line combined with the R26YFPR reporter line we are able to fluorescently label the melanoblast population within these skin cultures. The technique allows live-imaging of melanoblasts and observation of their behavior and interactions with the tissue in which they develop. Representative results are included to demonstrate the capability to live-image 6 cultures in parallel. PMID:24894489

  11. Topical treatment with coenzyme Q10-containing formulas improves skin's Q10 level and provides antioxidative effects.

    PubMed

    Knott, Anja; Achterberg, Volker; Smuda, Christoph; Mielke, Heiko; Sperling, Gabi; Dunckelmann, Katja; Vogelsang, Alexandra; Krüger, Andrea; Schwengler, Helge; Behtash, Mojgan; Kristof, Sonja; Diekmann, Heike; Eisenberg, Tanya; Berroth, Andreas; Hildebrand, Janosch; Siegner, Ralf; Winnefeld, Marc; Teuber, Frank; Fey, Sven; Möbius, Janne; Retzer, Dana; Burkhardt, Thorsten; Lüttke, Juliane; Blatt, Thomas

    2015-01-01

    Ubiquinone (coenzyme Q10, Q10) represents an endogenously synthesized lipid-soluble antioxidant which is crucial for cellular energy production but is diminished with age and under the influence of external stress factors in human skin. Here, it is shown that topical Q10 treatment is beneficial with regard to effective Q10 replenishment, augmentation of cellular energy metabolism, and antioxidant effects. Application of Q10-containing formulas significantly increased the levels of this quinone on the skin surface. In the deeper layers of the epidermis the ubiquinone level was significantly augmented indicating effective supplementation. Concurrent elevation of ubiquinol levels suggested metabolic transformation of ubiquinone resulting from increased energy metabolism. Incubation of cultured human keratinocytes with Q10 concentrations equivalent to treated skin showed a significant augmentation of energy metabolism. Moreover, the results demonstrated that stressed skin benefits from the topical Q10 treatment by reduction of free radicals and an increase in antioxidant capacity.

  12. Topical treatment with coenzyme Q10-containing formulas improves skin's Q10 level and provides antioxidative effects.

    PubMed

    Knott, Anja; Achterberg, Volker; Smuda, Christoph; Mielke, Heiko; Sperling, Gabi; Dunckelmann, Katja; Vogelsang, Alexandra; Krüger, Andrea; Schwengler, Helge; Behtash, Mojgan; Kristof, Sonja; Diekmann, Heike; Eisenberg, Tanya; Berroth, Andreas; Hildebrand, Janosch; Siegner, Ralf; Winnefeld, Marc; Teuber, Frank; Fey, Sven; Möbius, Janne; Retzer, Dana; Burkhardt, Thorsten; Lüttke, Juliane; Blatt, Thomas

    2015-01-01

    Ubiquinone (coenzyme Q10, Q10) represents an endogenously synthesized lipid-soluble antioxidant which is crucial for cellular energy production but is diminished with age and under the influence of external stress factors in human skin. Here, it is shown that topical Q10 treatment is beneficial with regard to effective Q10 replenishment, augmentation of cellular energy metabolism, and antioxidant effects. Application of Q10-containing formulas significantly increased the levels of this quinone on the skin surface. In the deeper layers of the epidermis the ubiquinone level was significantly augmented indicating effective supplementation. Concurrent elevation of ubiquinol levels suggested metabolic transformation of ubiquinone resulting from increased energy metabolism. Incubation of cultured human keratinocytes with Q10 concentrations equivalent to treated skin showed a significant augmentation of energy metabolism. Moreover, the results demonstrated that stressed skin benefits from the topical Q10 treatment by reduction of free radicals and an increase in antioxidant capacity. PMID:26648450

  13. Development of a Bioengineered Skin-Humanized Mouse Model for Psoriasis

    PubMed Central

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

    2010-01-01

    Over the past few years, whole skin xenotransplantation models that mimic different aspects of psoriasis have become available. However, these models are strongly constrained by the lack of skin donor availability and homogeneity. We present in this study a bioengineering-based skin-humanized mouse model for psoriasis, either in an autologous version using samples derived from psoriatic patients or, more importantly, in an allogeneic context, starting from skin biopsies and blood samples from unrelated healthy donors. After engraftment, the regenerated human skin presents the typical architecture of normal human skin but, in both cases, immunological reconstitution through intradermal injection in the regenerated skin using in vitro-differentiated T1 subpopulations as well as recombinant IL-17 and IL-22 Th17 cytokines, together with removal of the stratum corneum barrier by a mild abrasive treatment, leads to the rapid conversion of the skin into a bona fide psoriatic phenotype. Major hallmarks of psoriasis were confirmed by the evaluation of specific epidermal differentiation and proliferation markers as well as the mesenchymal milieu, including angiogenesis and infiltrate. Our bioengineered skin-based system represents a robust platform to reliably assess the molecular and cellular mechanisms underlying the complex interdependence between epidermal cells and the immune system. The system may also prove suitable to assess preclinical studies that test the efficacy of novel therapeutic treatments and to predict individual patient response to therapy. PMID:20971736

  14. [6]-Gingerol inhibits COX-2 expression by blocking the activation of p38 MAP kinase and NF-kappaB in phorbol ester-stimulated mouse skin.

    PubMed

    Kim, Sue Ok; Kundu, Joydeb Kumar; Shin, Young Kee; Park, Jin-Hong; Cho, Myung-Haing; Kim, Tae-Yoon; Surh, Young-Joon

    2005-04-01

    [6]-Gingerol, a pungent ingredient of ginger (Zingiber officinale Roscoe, Zingiberaceae), has a wide array of pharmacologic effects. The present study was aimed at unraveling the molecular mechanisms underlying previously reported antitumor promoting effects of [6]-gingerol in mouse skin in vivo. One of the well-recognized molecular targets for chemoprevention is cyclooxygenase-2 (COX-2) that is abnormally upregulated in many premalignant and malignant tissues and cells. In our present study, topical application of [6]-gingerol inhibited COX-2 expression in mouse skin stimulated with a prototype tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Since the transcription factor nuclear factor-kappaB (NF-kappaB) is known to regulate COX-2 induction, we attempted to determine the effect of [6]-gingerol on TPA-induced activation of NF-kappaB. Pretreatment with [6]-gingerol resulted in a decrease in both TPA-induced DNA binding and transcriptional activities of NF-kappaB through suppression of IkappaBalpha degradation and p65 nuclear translocation. Phosphorylation of both IkappaBalpha and p65 was substantially blocked by [6]-gingerol. In addition, [6]-gingerol inhibited TPA-stimulated interaction of phospho-p65-(Ser-536) with cAMP response element binding protein-binding protein, a transcriptional coactivator of NF-kappaB. Moreover, [6]-gingerol prevented TPA-induced phosphorylation and catalytic activity of p38 mitogen-activated protein (MAP) kinase that regulates COX-2 expression in mouse skin. The p38 MAP kinase inhibitor SB203580 attenuated NF-kappaB activation and subsequent COX-2 induction in TPA-treated mouse skin. Taken together, our data suggest that [6]-gingerol inhibits TPA-induced COX-2 expression in mouse skin in vivo by blocking the p38 MAP kinase-NF-kappaB signaling pathway. PMID:15735738

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

    PubMed

    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.

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

    PubMed

    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.

  17. A Review of the Use of Topical Calendula in the Prevention and Treatment of Radiotherapy-Induced Skin Reactions.

    PubMed

    Kodiyan, Joyson; Amber, Kyle T

    2015-01-01

    Calendula is a topical agent derived from a plant of the marigold family Calendula Officinalis. Containing numerous polyphenolic antioxidants, calendula has been studied in both the laboratory and clinical setting for the use in treating and preventing radiation induced skin toxicity. Despite strong evidence in the laboratory supporting calendula's mechanism of action in preventing radiation induced skin toxicity, clinical studies have demonstrated mixed results. In light of the controversy surrounding the efficacy of calendula in treating and preventing radiodermatitis, the topic warrants further discussion. PMID:26783706

  18. A Review of the Use of Topical Calendula in the Prevention and Treatment of Radiotherapy-Induced Skin Reactions.

    PubMed

    Kodiyan, Joyson; Amber, Kyle T

    2015-01-01

    Calendula is a topical agent derived from a plant of the marigold family Calendula Officinalis. Containing numerous polyphenolic antioxidants, calendula has been studied in both the laboratory and clinical setting for the use in treating and preventing radiation induced skin toxicity. Despite strong evidence in the laboratory supporting calendula's mechanism of action in preventing radiation induced skin toxicity, clinical studies have demonstrated mixed results. In light of the controversy surrounding the efficacy of calendula in treating and preventing radiodermatitis, the topic warrants further discussion.

  19. A Review of the Use of Topical Calendula in the Prevention and Treatment of Radiotherapy-Induced Skin Reactions

    PubMed Central

    Kodiyan, Joyson; Amber, Kyle T.

    2015-01-01

    Calendula is a topical agent derived from a plant of the marigold family Calendula Officinalis. Containing numerous polyphenolic antioxidants, calendula has been studied in both the laboratory and clinical setting for the use in treating and preventing radiation induced skin toxicity. Despite strong evidence in the laboratory supporting calendula’s mechanism of action in preventing radiation induced skin toxicity, clinical studies have demonstrated mixed results. In light of the controversy surrounding the efficacy of calendula in treating and preventing radiodermatitis, the topic warrants further discussion. PMID:26783706

  20. Influence of the hair cycle on the thickness of mouse skin

    SciTech Connect

    Hansen, L.S.; Coggle, J.E.; Wells, J.; Charles, M.W.

    1984-12-01

    The data on mouse skin thickness reported here was prompted by the need to know the true position of basal cells of the epidermis and hair follicles as these are important cells at risk for a variety of skin reactions including carcinogenesis following exposure to radiation. There is little reliable data in the literature and most previous reports have ignored the shrinkage of skin that occurs because of its natural elasticity. The values determined for mouse flank skin in telogen--the resting phase of the hair cycle for the different skin layers--are epidermis 10 micron, corium 250 micron, adipose layer 150 micron, and hair follicle depth 150 micron. Three days after chemical depilation which triggers the hair follicles into active cycle (anagen) the epidermis doubles in thickness, remains at this value for 7 days, and then gradually returns to telogen values by day 18. The corium and adipose layers also increase significantly to reach approximately 390 micron and approximately 260 micron, respectively, by day 10 and then return to control values from day 15 onward. The change in hair follicles depths are more dramatic with active follicle basal cells reaching approximately 450-550 micron into the adipose layer between days 7 and 15. One important finding is that chemical depilation does not affect the telogen thickness of skin-the teleogen values for the epidermis and dermis immediately prior to and immediately after depilation were similar to those 23 days later at the beginning of the next telogen phase.

  1. Quantification of epidermal histological changes induced by topical retinoids and CD271 in the rhino mouse model using a standardized image analysis technique.

    PubMed

    Bouclier, M; Chatelus, A; Ferracin, J; Delain, C; Shroot, B; Hensby, C N

    1991-01-01

    The rhino mouse has been used as an experimental model to screen topically active comedolytic agents. Adult rhino mice were treated on the back once daily for 5 consecutive days per week during 3 weeks. Skin histological preparations were analyzed by image analysis techniques to quantify the number of epidermal comedones, comedo profile and epidermal thickness. Using both a negative (treated with acetone) and a positive (treated with Aberel gel 0.025%) control group of animals in all experiments conducted over a period of about 3 years, we defined the upper and lower limit of acceptability of the results. Topical treatment with an acetone solution of all-trans retinoic acid (0.01, 0.03, 0.1%) and 13-cis-retinoic acid (0.1%) induced comedolysis and a marked increase in epidermal thickness. Commercial preparations of all-trans retinoic acid (Aberel lotion, gel and cream, Retin A cream, Retacnyl cream) presented a similar comedolytic activity. However, the epidermal thickening was higher with Retin A and weaker with Retacnyl. CD271, a new modulator of cell differentiation, applied either in acetone solution (0.01, 0.1%) or in lotion, gel or cream formulations (0.1%) also demonstrated a marked activity (i.e. comedolysis and epidermal thickening). These data confirm that the rhino mouse model can be used to assay drugs applied either in solvent or in topical formulations. Activity in this model compares favorably with published clinical observations in the treatment of acne.

  2. Topical negative pressure coupled with split-thickness skin grafting for the treatment of hidradenitis suppurativa: a case report.

    PubMed

    Jianbing, Tang; Biao, Cheng; Qin, Li; Yanhong, Wu

    2015-06-01

    Hidradenitis suppurativa is a cutaneous, chronic, recurrent inflammatory disease. Here, we report the case of a 66-year-old man who had hidradenitis suppurativa in the buttocks. He suffered from diabetes mellitus. In the past, he had perianal abscesses. Because of improper treatment of furuncle infections in the buttocks, skin ulcers formed, which worsened and resulted in multiple fistulas. The skin lesion surface was large and the infection was severe. After wound debridement treatment, topical negative pressure and nutritional support were given. After one and a half months, the wound healed with split-thickness skin grafting. In a 2-year follow-up, there was no evidence of hidradenitis suppurativa recurrence.

  3. Transcriptional changes in organoculture of full-thickness human skin following topical application of all-trans retinoic acid.

    PubMed

    Gillbro, J M; Al-Bader, T; Westman, M; Olsson, M J; Mavon, A

    2014-06-01

    In this study, we developed an organoculture of human skin to investigate the effect of topical applied all-trans retinoic acid using a gene array approach. We could by using this approach confirm previous studies on genes activated by RA in keratinocyte monocultures and also provide new insights on genes that are relevant to RA-activation in human skin. The results in the present study show this model represent a valuable pre-clinical model for studying the effects of retinoids in skin. PMID:24697191

  4. The circadian clock controls sunburn apoptosis and erythema in mouse skin.

    PubMed

    Gaddameedhi, Shobhan; Selby, Christopher P; Kemp, Michael G; Ye, Rui; Sancar, Aziz

    2015-04-01

    Epidemiological studies of humans and experimental studies with mouse models suggest that sunburn resulting from exposure to excessive UV light and damage to DNA confers an increased risk for melanoma and non-melanoma skin cancer. Previous reports have shown that both nucleotide excision repair, which is the sole pathway in humans for removing UV photoproducts, and DNA replication are regulated by the circadian clock in mouse skin. Furthermore, the timing of UV exposure during the circadian cycle has been shown to affect skin carcinogenesis in mice. Because sunburn and skin cancer are causally related, we investigated UV-induced sunburn apoptosis and erythema in mouse skin as a function of circadian time. Interestingly, we observed that sunburn apoptosis, inflammatory cytokine induction, and erythema were maximal following an acute early-morning exposure to UV and minimal following an afternoon exposure. Early-morning exposure to UV also produced maximal activation of ataxia telangiectasia mutated and Rad3-related (Atr)-mediated DNA damage checkpoint signaling, including activation of the tumor suppressor p53, which is known to control the process of sunburn apoptosis. These data provide early evidence that the circadian clock has an important role in the erythemal response in UV-irradiated skin. The early morning is when DNA repair is at a minimum, and thus the acute responses likely are associated with unrepaired DNA damage. The prior report that mice are more susceptible to skin cancer induction following chronic irradiation in the AM, when p53 levels are maximally induced, is discussed in terms of the mutational inactivation of p53 during chronic irradiation.

  5. Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NF-kappaB in mouse skin by blocking IkappaB kinase activity.

    PubMed

    Kundu, Joydeb Kumar; Shin, Young Kee; Kim, Sung Hoon; Surh, Young-Joon

    2006-07-01

    Aberrant expression of cyclooxygenase-2 (COX-2) has been implicated in tumor promotion. Resveratrol, a phytoalexin present in grapes, was reported to inhibit multistage mouse skin carcinogenesis. In the present study, we found that topically applied resveratrol significantly inhibited COX-2 expression induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Resveratrol-suppressed phosphorylation and subsequent degradation of IkappaBalpha, thereby inhibiting activation of nuclear factor-kappaB (NF-kappaB) in TPA-stimulated mouse skin. Pretreatment with resveratrol also suppressed TPA-induced phosphorylation of extracellular signal-regulated protein kinase (ERK) and p38 mitogen-activated protein (MAP) kinase. Resveratrol blunted TPA-induced phosphorylation of p65 and its interaction with CBP/p300, rendering NF-kappaB transcriptionally inactive. To get further insights into the molecular basis of NF-kappaB inactivation by resveratrol, we examined the role of IkappaB kinase (IKK) in mediating TPA-induced activation of NF-kappaB and COX-2 expression. TPA treatment led to rapid induction of IKK activity in mouse skin, which was abolished either by resveratrol or an IKK inhibitor Bay 11-7082. Topical application of Bay 11-7082 also abrogated TPA-induced NF-kappaB activation and COX-2 expression, supporting the involvement of IKK in TPA-induced COX-2 expression. Taken together, the above findings suggest that resveratrol targets IKK in blocking TPA-induced NF-kappaB activation and COX-2 expression in mouse skin in vivo.

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

    PubMed Central

    Stewart, Eranée; Ajao, Moyosore Salihu

    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. 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. PMID:24288469

  7. Differential effects of topically applied formalin and aromatic compounds on neurogenic-mediated microvascular leakage in rat skin.

    PubMed

    Futamura, Masaki; Goto, Shiho; Kimura, Ryoko; Kimoto, Izumi; Miyake, Mio; Ito, Komei; Sakamoto, Tatsuo

    2009-01-01

    Various volatile organic compounds (VOCs) act as a causative agent of skin inflammation. We investigated the effect of topical application of several VOCs and formalin on microvascular leakage in rat skin. We tested capsaicin, which is a reagent that specifically causes the skin response via endogenously released tachykinins. Evans blue dye extravasation served as an index of the increase in skin vascular permeability. After shaving the abdomen, we applied formalin, m-xylene, toluene, styrene, benzene, ethylbenzene, acetone, diethyl ether, hexane, heptane, cyclohexane and capsaicin to the skin. At 40min after application, skin samples were collected. Among all of the VOCs tested, all of the aromatic compounds significantly produced skin microvascular leakage that was similar to formalin and capsaicin. We also investigated the skin responses seen after the intravenous administration of CP-99,994 (1.5 or 5mg/kg), which is a tachykinin NK1 receptor antagonist, ketotifen (1 or 3mg/kg), which is a histamine H1 receptor antagonist that stabilizes the mast cells, and the topical application of capsazepine (22.5 or 50mM), which is the transient receptor potential vanilloid 1 (TRPV1) antagonist. The response induced by formalin and capsaicin was completely inhibited by CP-99,994. On the other hand, the antagonist partially reduced the response induced by m-xylene, toluene and styrene by 39%, 50% and 46%, respectively. Capsazepine and ketotifen did not alter the response induced by formalin or any of the aromatic compounds. Like capsaicin, formalin and the aromatic compounds at least partially caused skin microvascular leakage, which was due to tachykinin NK1 receptor activation related to the release of tachykinins from the sensory nerve endings. However, it is unlikely that mast cells and TRPV1 play an important role in the skin response.

  8. Novel skin phenotypes revealed by a genome-wide mouse reverse genetic screen

    PubMed Central

    Liakath-Ali, Kifayathullah; Vancollie, Valerie E.; Heath, Emma; Smedley, Damian P.; Estabel, Jeanne; Sunter, David; DiTommaso, Tia; White, Jacqueline K.; Ramirez-Solis, Ramiro; Smyth, Ian; Steel, Karen P.; Watt, Fiona M.

    2014-01-01

    Permanent stop-and-shop large-scale mouse mutant resources provide an excellent platform to decipher tissue phenogenomics. Here we analyse skin from 538 knockout mouse mutants generated by the Sanger Institute Mouse Genetics Project. We optimize immunolabelling of tail epidermal wholemounts to allow systematic annotation of hair follicle, sebaceous gland and interfollicular epidermal abnormalities using ontology terms from the Mammalian Phenotype Ontology. Of the 50 mutants with an epidermal phenotype, 9 map to human genetic conditions with skin abnormalities. Some mutant genes are expressed in the skin, whereas others are not, indicating systemic effects. One phenotype is affected by diet and several are incompletely penetrant. In-depth analysis of three mutants, Krt76, Myo5a (a model of human Griscelli syndrome) and Mysm1, provides validation of the screen. Our study is the first large-scale genome-wide tissue phenotype screen from the International Knockout Mouse Consortium and provides an open access resource for the scientific community. PMID:24721909

  9. SENCAR mouse skin tumorigenesis model versus other strains and stocks of mice

    SciTech Connect

    Slaga, T.J.

    1986-09-01

    The SENCAR mouse stock was selectively bred for eight generations for sensitivity to skin tumor induction by the two-stage tumorigenesis protocol using 7,12-dimethylbenz(a)anthracene (DMBA) as the initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter. The SENCAR mouse was derived by crossing Charles River CD-1 mice with skin-tumor-sensitive mice (STS). The SENCAR mice are much more sensitive to both DMBA tumor initiation and TPA tumor promotion than CD-1, BALB/c, and DBA/2 mice. An even greater difference in the sensitivity to two-stage skin tumorigenesis is apparent between SENCAR and C57BL/6 mice when using DMBA-TPA treatment. However, the SENCAR and C57BL/6 mice have a similar tumor response to DMBA-benzoyl peroxide treatment, suggesting that TPA is not an effective promoter in C57BL/6 mice. The DBA/2 mice respond in a similar manner to the SENCAR mice when using N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-TPA treatment. The SENCAR mouse model provides a good dose-response relationship for many carcinogens used as tumor initiators and for many compounds used as tumor promoter. When compared to other stocks and strains of mice, the SENCAR mouse has one of the largest data bases for carcinogens and promoters.

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

    PubMed

    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

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

    PubMed

    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.

  12. 1'-Acetoxychavicol acetate, a superoxide anion generation inhibitor, potently inhibits tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in ICR mouse skin.

    PubMed

    Murakami, A; Ohura, S; Nakamura, Y; Koshimizu, K; Ohigashi, H

    1996-01-01

    The anti-tumor-promoting activity of 1'-acetoxychavicol acetate (ACA) was examined in a two-stage carcinogenesis experiment in ICR mouse skin using 7,12-dimethylbenz[a]anthracene (0.19 mumol) and 12-O-tetradecanoylphorbol-13-acetate (TPA; 1.6 nmol). Topical application of ACA (160 nmol) markedly reduced the average number of tumors per mouse and the ratio of tumor-bearing mice: inhibition ratios 90% (p < 0.001) and 42% (p < 0.005), respectively. ACA even at a dose equimolar to TPA (1.6 nmol) significantly reduced the average number of tumors per mouse: inhibitory ratio 44% (p < 0.05). ACA potently inhibited TPA-induced superoxide (O2-) generation in differentiated HL-60 cells (IC50 = 4.3 microM) and suppressed the lipid hydroperoxide formation by 42% (p < 0.001) in the ethyl linoleate autoxidation test.

  13. Micropatch-arrayed pads for non-invasive spatial and temporal profiling of topical drugs on skin surface.

    PubMed

    Dutkiewicz, Ewelina P; Chiu, Hsien-Yi; Urban, Pawel L

    2015-11-01

    Micropatch-arrayed pads (MAPAs) are presented as a facile and sensitive sampling method for spatial profiling of topical agents adsorbed on the surface of skin. MAPAs are 28 × 28 mm sized pieces of polytetrafluoroethylene containing plurality of cavities filled with agarose hydrogel. They are affixed onto skin for 10 min with the purpose to collect drugs applied topically. Polar compounds are absorbed by the hydrogel micropatches. The probes are subsequently scanned by an automated nanospray desorption electrospray ionization mass spectrometry system operated in the tapping dual-polarity mode. When the liquid junction gets into contact with every micropatch, polar compounds absorbed in the hydrogel matrix are desorbed and transferred to the ion source. A 3D-printed interface prevents evaporation of hydrogel micropatches assuring good reproducibility and sensitivity. MAPAs have been applied to follow dispersion of topical drugs applied to human skin in vivo and to porcine skin ex vivo, in the form of self-adhesive patches. Spatiotemporal characteristics of the drug dispersion process have been revealed using this non-invasive test. Differences between drug dispersion in vivo and ex vivo could be observed. We envision that MAPAs can be used to investigate spatiotemporal kinetics of various topical agents utilized in medical treatment. PMID:26505778

  14. Defining the clonal dynamics leading to mouse skin tumour initiation.

    PubMed

    Sánchez-Danés, Adriana; Hannezo, Edouard; Larsimont, Jean-Christophe; Liagre, Mélanie; Youssef, Khalil Kass; Simons, Benjamin D; Blanpain, Cédric

    2016-08-18

    The changes in cell dynamics after oncogenic mutation that lead to the development of tumours are currently unknown. Here, using skin epidermis as a model, we assessed the effect of oncogenic hedgehog signalling in distinct cell populations and their capacity to induce basal cell carcinoma, the most frequent cancer in humans. We found that only stem cells, and not progenitors, initiated tumour formation upon oncogenic hedgehog signalling. This difference was due to the hierarchical organization of tumour growth in oncogene-targeted stem cells, characterized by an increase in symmetric self-renewing divisions and a higher p53-dependent resistance to apoptosis, leading to rapid clonal expansion and progression into invasive tumours. Our work reveals that the capacity of oncogene-targeted cells to induce tumour formation is dependent not only on their long-term survival and expansion, but also on the specific clonal dynamics of the cancer cell of origin. PMID:27459053

  15. A supramolecular topical gel derived from a non-steroidal anti-inflammatory drug, fenoprofen, is capable of treating skin inflammation in mice.

    PubMed

    Majumder, Joydeb; Yedoti, Pavani; Dastidar, Parthasarathi

    2015-02-28

    A new series of bioconjugates derived from a non-steroidal anti-inflammatory drug (NSAID), namely fenoprofen, has been synthesised by amidation with various biogenic molecules such as β-alanine, aminocaproic acid and tyramine with the aim of converting the NSAID into a supramolecular gelator for plausible biomedical applications. One such bioconjugate (2) showed gelation ability with methylsalicylate (MS) and 1% menthol in methyl salicylate (MMS) solvents. These gels were characterized by table top rheology, high resolution-transmission electron microscopy (HR-TEM) and dynamic rheology. Gelator 2 was found to be biostable both in proteolytic enzymes and in blood serum of BALB/c mouse under physiological conditions. It was also found to be biocompatible, as revealed by the methyl thiazolyldiphenyl tetrazolium bromide (MTT) assay in mouse macrophage RAW 264.7 and mouse myoblast C2C12 cells. The anti-inflammatory response (prostaglandin E2 assay, denoted PGE2 assay) of 2 was comparable to that of the parent drug fenoprofen calcium salt. Finally, a topical gel formulation of 2 displayed in vivo self-delivery application in treating imiquimod (IMQ) induced skin inflammation in BALB/c mice. PMID:25554116

  16. Topical anaesthesia does not affect cutaneous vasomotor or sudomotor responses in human skin.

    PubMed

    Metzler-Wilson, K; Wilson, T E

    2013-10-01

    (1) The effects of local sensory blockade (topical anaesthesia) on eccrine sweat glands and cutaneous circulation are not well understood. This study aimed to determine whether topical lidocaine/prilocaine alters eccrine sweat gland and cutaneous blood vessel responses. (2) Sweating (capacitance hygrometry) was induced via forearm intradermal microdialysis of five acetylcholine (ACh) doses (1 × 10(-4) to 1 × 10(0) m, 10-fold increments) in control and treated forearm sites in six healthy subjects. Nitric oxide-mediated vasodilatory (sodium nitroprusside) and adrenergic vasoconstrictor (noradrenaline) agonists were iontophoresed in lidocaine/prilocaine-treated and control forearm skin in nine healthy subjects during blood flow assessment (laser Doppler flowmetry, expressed as% from baseline cutaneous vascular conductance; CVC; flux/mean arterial pressure). (3) Non-linear regression curve fitting identified no change in the ED50 of ACh-induced sweating after sensory blockade (-1.42 ± 0.23 logM) compared to control (-1.27 ± 0.23 logM; P > .05) or in Emax (0.43 ± 0.08 with, 0.53 ± 0.16 mg cm(-2) min(-1) without lidocaine/prilocaine; P > .05). Sensory blockade did not alter the vasodilator response to sodium nitroprusside (1280 ± 548% change from baseline CVC with, 1204 ± 247% without lidocaine/prilocaine) or vasoconstrictor response to noradrenaline (-14 ± 4% change from baseline CVC with, -22 ± 14% without lidocaine/prilocaine; P > 0.05). (4) Cutaneous sensory blockade does not appear to alter nitric oxide-mediated vasodilation, adrenergic vasoconstriction, or cholinergic eccrine sweating dose-response sensitivity or responsiveness to maximal dose. Thus, lidocaine/prilocaine treatment should not affect sweat gland function or have blood flow implications for subsequent research protocols or clinical procedures.

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

    PubMed Central

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

    2013-01-01

    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. PMID:23907528

  18. Adiponectin resides in mouse skin and upregulates hyaluronan synthesis in dermal fibroblasts.

    PubMed

    Akazawa, Yumiko; Sayo, Tetsuya; Sugiyama, Yoshinori; Sato, Takashi; Akimoto, Noriko; Ito, Akira; Inoue, Shintaro

    2011-01-01

    Adipose tissue is a hormonally active tissue that produces adipokines that influence the activity of other tissues. Adiponectin is an adipocyte-specific adipokine involved in systemic metabolism. We detected the expression of adiponectin receptors (AdipoR1 and AdipoR2) mRNA in cultured dermal fibroblasts. The full-length adiponectin (fAd), but not the globular adiponectin (gAd), increased hyaluronan (HA) production and upregulated HA synthase (HAS) 2 mRNA expression. AdipoR1 and AdipoR2 mRNAs were also expressed in keratinocytes, though neither fAd nor gAd had any effect on HA synthesis. In mouse skin, we found that adiponectin was present and decreased markedly with aging. The age-dependent pattern of adiponectin decrease in skin, correlated well with that of HA in skin. Our experiments were also the first to identify adiponectin production in cultured mouse sebocytes, a finding that suggests that skin adiponectin may derive not only from plasma and/or subcutaneous adipose tissue, but also from the sebaceous gland. These results indicated that adiponectin plays an important role in the HA metabolism of skin. PMID:21117904

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

    NASA Astrophysics Data System (ADS)

    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.

  20. What happens in the skin? Integrating skin permeation kinetics into studies of developmental and reproductive toxicity following topical exposure.

    PubMed

    Dancik, Yuri; Bigliardi, Paul L; Bigliardi-Qi, Mei

    2015-12-01

    Animal-based developmental and reproductive toxicological studies involving skin exposure rarely incorporate information on skin permeation kinetics. For practical reasons, animal studies cannot investigate the many factors which can affect human skin permeation and systemic uptake kinetics in real-life scenarios. Traditional route-to-route extrapolation is based on the same types of experiments and requires assumptions regarding route similarity. Pharmacokinetic modeling based on skin physiology and structure is the most efficient way to incorporate the variety of intrinsic skin and exposure-dependent parameters occurring in clinical and occupational settings into one framework. Physiologically-based pharmacokinetic models enable the integration of available in vivo, in vitro and in silico data to quantitatively predict the kinetics of uptake at the site of interest, as needed for 21st century toxicology and risk assessment. As demonstrated herein, proper interpretation and integration of these data is a multidisciplinary endeavor requiring toxicological, risk assessment, mathematical, pharmaceutical, biological and dermatological expertise.

  1. Topical application and uptake of vitamin E acetate by the skin and conversion to free vitamin E.

    PubMed

    Trevithick, J R; Mitton, K P

    1993-12-01

    Radioactive tocopherol acetate was diluted with either (1) unlabelled tocopherol acetate or (2) Delios S (Henkel, a medium chain triglyceride prepared from fractionated coconut oil), a cosmetic base. These preparations were applied topically to a 2 cm diameter circle of skin. After 24 hours the percent of label which was still removable by swabbing the skin surface was 1.7% for (1) and 11.5% for (2). The central circles contained 2.86% of the label applied in 259 mg skin for (1) and 24.2% of the label applied in 226 mg skin for Delios S for (2). Surprisingly, combined samples of approximately one third of the side skin contained 0.7% of the label applied in 460 mg for (1) and 13.2% of the applied label in one third of the side skin in 523 mg for (2). The percent conversion to tocopherol in the skin central areas was 4.52% by HPLC and 4.13% by TLC for (1) and 5.97% for (2). In the side skin the percent conversion to tocopherol was 5.0% for (1) and 6.01% for (2).

  2. Protection against induction of mouse skin papillomas with low and high risk of conversion to malignancy by green tea polyphenols.

    PubMed

    Katiyar, S K; Mohan, R R; Agarwal, R; Mukhtar, H

    1997-03-01

    We earlier showed that a polyphenolic fraction isolated from green tea (GTP) affords protection against tumor promotion and tumor progression in SENCAR mouse skin. The present study was designed to further evaluate the protective effect of GTP against the induction and subsequent progression of papillomas to squamous cell carcinomas (SCCs) in experimental protocols where papillomas were developed with a low or high probability of their malignant conversion. Topical application of GTP (6 mg/animal) 30 min prior to that of 12-O-tetradecanoylphorbol-13-acetate (TPA) either once a week for 5 weeks (high risk TPA protocol) or once a week for 20 weeks (low risk TPA protocol) or mezerein (MEZ) twice a week for 20 weeks (high risk MEZ protocol) in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin resulted in significant protection against skin tumor promotion in terms of tumor incidence (32-60%), multiplicity (49-63%) and tumor volume/mouse (73-90%) at the termination of the experiment at 20 weeks. In three separate malignant progression experiments when papilloma yield in DMBA-initiated and TPA or MEZ promoted low and high risk protocols was stabilized at 20 weeks, animals were divided into two subgroups. These animals were either topically treated twice weekly with acetone (0.2 ml/animal, spontaneous malignant conversion group) or with GTP (6 mg/animal in 0.2 ml acetone) for an additional period of 31 weeks. During these treatment regimens, all suspected carcinomas were recorded and each one was verified histopathologically either at the time when tumor-bearing mouse died/moribund or at the termination of the experiment at 51 weeks. GTP resulted in significant protection against the malignant conversion of papillomas to SCC in all the protocols employed. At the termination of the experiment at 51 weeks, these protective effects were evident in terms of mice with carcinomas (35-41%), carcinomas per mouse (47-55%) and percent malignant conversion of papillomas to

  3. Micronuclei in mouse skin cells following in vivo exposure to benzo(a)pyrene, 7,12-dimethylbenz(a)anthracene, chrysene, pyrene and urethane

    SciTech Connect

    Shuilin He ); Baker, R. )

    1991-01-01

    Detection of micronuclei (MN) in skin cells from HRA/Skh hairless mice treated with chemical or physical agents may prove informative in qualitative and quantitative studies of skin carcinogenesis. MN induction and cell survival were estimated in cytokinesis-blocked keratinocytes, cultured for 4 days in vitro, after a single topical dose of various organic compounds. Treatment with 7,12-dimethylbenz(a)anthracene (DMBA) resulted in maximal MN induction in cells removed from skin 12-24 hr after topical administration. Even in cells removed only 1 hr after DMBA treatment, a significant increase in MN was evident. However, to allow sufficient time for metabolic activation, a sampling time of 24 hr was adopted for all test substances. Dose-dependent increases in MN were observed with DMBA, benzo(a)pyrene, chrysene, and urethane. Increased numbers of micronucleated cells were detected at the lowest doses administered in the present study. Although reduced cell recovery occurred following exposure of mice to acetone, pyrene, and other chemicals, there was no evidence that cytotoxicity contributed to MN scored in keratinocytes. Moreover, the probable noncarcinogen, pyrene, failed to induce MN at doses from 2.5 {mu}g to 2.5 mg/mouse. These results show that it is possible to assess chemical exposure in skin by measuring cell survival and skin genotoxicity by measuring MN induction in cultured keratinocytes.

  4. Development of dry skin in the NOA mouse under individual housing conditions: a potentially useful animal model for evaluating moisturizing effects.

    PubMed

    Kondo, Taizo; Ohno, Hitoshi; Kondo, Toshio; Shiomoto, Yasuhisa; Momii, Akira

    2005-10-01

    In a previous study, we reported the development of grossly observable dry skin in all of the Naruto Research Institute Otsuka Atrichia (NOA) mice that were housed individually. In the present study, dermal physiological function tests were conducted and the usefulness of this dry skin model for evaluating the efficacy of topical moisturizers was assessed. As a result, we have confirmed a marked reduction in the water content of the stratum corneum in these animals. Therefore, the development of dry skin in the NOA mouse strain under individual housing conditions may be expected to serve as a useful animal model for evaluating topical moisturizers. Specifically, the water content of the stratum corneum was restored in proportion to the oil content of the ointment base used to treat the animals, and the moisturizing effects of urea were confirmed in animals treated with urea-containing ointment. In addition, when the animals that had been housed individually were returned to group housing conditions, the water content of the stratum corneum was restored, with a corresponding improvement in dry skin. This finding suggests that socio-psychological factors are involved in the etiology of dry skin in individually housed NOA mice. PMID:16365520

  5. Topical Application of Angelica sinensis Improves Pruritus and Skin Inflammation in Mice with Atopic Dermatitis-Like Symptoms.

    PubMed

    Lee, Jaehong; Choi, You Yeon; Kim, Mi Hye; Han, Jae Min; Lee, Ji Eun; Kim, Eun Hye; Hong, Jongki; Kim, Jinju; Yang, Woong Mo

    2016-01-01

    Angelica sinensis (AS) is one of the most popular medicinal foods used as a hematopoietic herb and also traditionally applied topically for skin disorders. However, the effectiveness of AS on atopic dermatitis (AD) has not been reported yet. This study was conducted to evaluate the antipruritic and anti-inflammatory effects of AS on regulating AD-related mediators in DNCB (2,4-dinitrochlorobenzene)-induced mice. AS was topically applied to the dorsal skin of DNCB-challenged mice for 11 days. Alteration of skin thickness was measured for assessment of histological improvement. In addition, the number of mast cells, the level of serum immunoglobulin E (IgE), the counting of scratching behavior, and the expression of substance P were evaluated. Also, the expressions of cytokines, nuclear factor κB (NF-κB), phospho-IκBα, and mitogen-activated protein kinases (MAPKs) were measured for evaluating the improvement of skin inflammation. The repeated treatment of AS significantly inhibited the skin thickness, the number of mast cells, and the level of serum IgE. Moreover, AS significantly suppressed the increased scratching behavior and the expression of substance P compared to the DNCB group. Topical application of AS also reduced the level of cytokines (IL-4, IL-6, TNF-α, and IFN-γ) as well as the expressions of NF-κB, phospho-IκBα, and phospho-MAPKs in the dorsal skin. The results of our study suggest that topical application of AS might have efficacy for modulating pruritus and inflammation in AD. Further studies are required to further characterize the mechanism of actions of AS.

  6. Measuring the effects of topically applied skin optical clearing agents and modeling the effects and consequences for laser therapies

    NASA Astrophysics Data System (ADS)

    Verkruysse, Wim; Khan, Misbah; Choi, Bernard; Svaasand, Lars O.; Nelson, J. Stuart

    2005-04-01

    Human skin prepared with an optical clearing agent manifests reduced scattering as a result of de-hydration and refractive index matching. This has potentially large effects for laser therapies of several skin lesions such as port wine stain, hair removal and tattoo removal. With most topically applied clearing agents the clearing effect is limited because they penetrate poorly through the intact superficial skin layer (stratum corneum). Agent application modi other than topical are impractical and have limited the success of optical clearing in laser dermatology. In recent reports, however, a mixture of lipofylic and hydrofylic agents was shown to successfully penetrate through the intact stratum corneum layer which has raised new interest in this field. Immediately after application, the optical clearing effect is superficial and, as the agent diffuses through the skin, reduced scattering is manifested in deeper skin layers. For practical purposes as well as to maximize therapeutic success, it is important to quantify the reduced scattering as well as the trans-cutaneous transport dynamics of the agent. We determined the time and tissue depth resolved effects of optically cleared skin by inserting a microscopic reflector array in the skin. Depth dependent light intensity was measured by quantifying the signal of the reflector array with optical coherence tomography. A 1-dimensional mass diffusion model was used to estimate a trans-cutaneous transport diffusion constant for the clearing agent mixture. The results are used in Monte Carlo modeling to determine the optimal time of laser treatment after topical application of the optical clearing agent.

  7. The Cutaneous Microbiome and Aspects of Skin Antimicrobial Defense System Resist Acute Treatment with Topical Skin Cleansers.

    PubMed

    Two, Aimee M; Nakatsuji, Teruaki; Kotol, Paul F; Arvanitidou, Evangelia; Du-Thumm, Laurence; Hata, Tissa R; Gallo, Richard L

    2016-10-01

    The human skin microbiome has been suggested to play an essential role in maintaining health by contributing to innate defense of the skin. These observations have inspired speculation that the use of common skin washing techniques may be detrimental to the epidermal antibacterial defense system by altering the microbiome. In this study, several common skin cleansers were used to wash human forearms and the short-term effect on the abundance of the antimicrobial peptide LL-37 and the abundance and diversity of bacterial DNA was measured. Despite small but significant decreases in the amount of LL-37 on the skin surface shortly after washing, no significant change in the bacterial community was detected. Furthermore, Group A Streptococcus did not survive better on the skin after washing. In contrast, the addition of antimicrobial compounds such as benzalkonium chloride or triclocarban to soap before washing decreased the growth of Group A Streptococcus applied after rinse. These results support prior studies that hand washing techniques in the health care setting are beneficial and should be continued. Additional research is necessary to better understand the effects of chronic washing and the potential impact of skin care products on the development of dysbiosis in some individuals. PMID:27377698

  8. Mouse Model of Cervicovaginal Toxicity and Inflammation for Preclinical Evaluation of Topical Vaginal Microbicides

    PubMed Central

    Catalone, Bradley J.; Kish-Catalone, Tina M.; Budgeon, Lynn R.; Neely, Elizabeth B.; Ferguson, Maelee; Krebs, Fred C.; Howett, Mary K.; Labib, Mohamed; Rando, Robert; Wigdahl, Brian

    2004-01-01

    Clinical trials evaluating the efficacy of nonoxynol-9 (N-9) as a topical microbicide concluded that N-9 offers no in vivo protection against human immunodeficiency virus type 1 (HIV-1) infection, despite demonstrated in vitro inactivation of HIV-1 by N-9. These trials emphasize the need for better model systems to determine candidate microbicide effectiveness and safety in a preclinical setting. To that end, time-dependent in vitro cytotoxicity, as well as in vivo toxicity and inflammation, associated with N-9 exposure were characterized with the goal of validating a mouse model of microbicide toxicity. In vitro studies using submerged cell cultures indicated that human cervical epithelial cells were inherently more sensitive to N-9-mediated damage than human vaginal epithelial cells. These results correlated with in vivo findings obtained by using Swiss Webster mice in which intravaginal inoculation of 1% N-9 or Conceptrol gel (containing 4% N-9) resulted in selective and acute disruption of the cervical columnar epithelial cells 2 h postapplication accompanied by intense inflammatory infiltrates within the lamina propria. Although damage to the cervical epithelium was apparent out to 8 h postapplication, these tissues resembled control tissue by 24 h postapplication. In contrast, minimal damage and infiltration were associated with both short- and long-term exposure of the vaginal mucosa to either N-9 or Conceptrol. These analyses were extended to examine the relative toxicity of polyethylene hexamethylene biguanide (PEHMB), a polybiguanide compound under evaluation as a candidate topical microbicide. In similar studies, in vivo exposure to 1% PEHMB caused minimal damage and inflammation of the genital mucosa, a finding consistent with the demonstration that PEHMB was >350-fold less cytotoxic than N-9 in vitro. Collectively, these studies highlight the murine model of toxicity as a valuable tool for the preclinical assessment of toxicity and inflammation

  9. Excised porcine skin experimental systems to validate quantitative microdialysis methods for determination of drugs in skin after topical application.

    PubMed

    Seki, Toshinobu; Wang, Aiping; Yuan, Dan; Saso, Yuko; Hosoya, Osamu; Chono, Sumio; Morimoto, Kazuhiro

    2004-11-24

    Microdialysis is useful as a method to evaluate the disposition of drugs in the skin to design improved transdermal delivery systems (TDDSs). In this study, quantitative microdialysis methods were validated in excised porcine skin experimental systems in vitro. Flurbiprofen (FP), used as a model drug, showed high affinity for the skin tissues in equilibrium states between the medium and skin. The membrane clearances of FP for permeation through the membrane of a dialysis fiber placed in the skin (CL(m in S)) were lower than that in the medium. The adsorption of components in the skin to the membrane surface of the dialysis fiber and accumulation of FP near the dialysis fiber are the most likely reasons for this. When CL(m in S) was used to predict the extracellular FP concentration in skin (C(T)), the value obtained was lower than that expected from the FP concentration in the medium on the dermis side, which should be equal to C(T) at equilibrium. In the zero net flux (ZNF) method, in which the concentration difference of perfusate (DeltaC) between the inflow and outflow were used to obtain C(T), the predicted C(T) was similar to the expected value. In an in vitro skin permeation experiment, the ZNF method was used for the prediction of C(T) near the dialysis fiber. The predicted C(T) was over 10 times higher than the FP concentration in the medium on the dermis side, suggesting a concentration gradient in the dermis. Although the ZNF method is good for predicting the C(T) in skin, the mass balance has to be considered for the quantitative evaluation of the skin permeation of drugs. In this study, the effect of the mass transfer of FP from the perfusate to the skin on the cumulative amount of FP passing through the skin was relatively low because of the use of suitable solutions as perfusate. The perfusion conditions and schedules should be designed carefully for quantitative evaluations using the ZNF method. These results provide useful information for the in

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

    PubMed

    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

  11. Effect of ointment bases on topical and transdermal delivery of salicylic acid in rats: evaluation by skin microdialysis.

    PubMed

    Murakami, T; Yoshioka, M; Okamoto, I; Yumoto, R; Higashi, Y; Okahara, K; Yata, N

    1998-01-01

    Microdialysis has been used to determine the concentration of salicylic acid in skin tissue and plasma periodically for 4 h to evaluate the effect of ointment bases on topical and transdermal delivery of salicylic acid. The ointment bases examined were solbase (water-soluble), poloid and white petrolatum (oleaginous), hydrophilic poloid (water in oil (w/o) type emulsion lacking water) and absorptive ointment (w/o-type emulsion containing water). The ointments (0.1 g) containing 25 micromol salicylic acid were applied for 2 h to the surface of rat skin (1 cm2) with (intact) or without the stratum corneum. For intact skin, the extent of topical delivery from different ointments, evaluated by the area under the concentration-time curve (AUC) of salicylic acid in the skin tissue (AUCskin), increased in the order solbase < white petrolatum, poloid, hydrophilic poloid < absorptive ointment. The ratio of AUCskin (topical delivery) to the AUC of salicylic acid in plasma (AUCplasma, transdermal delivery) varied remarkably among the different bases, the greatest ratio being observed for absorptive ointment. When the ointments were applied to skin surface without stratum corneum, AUCskin for solbase was much higher (about 45 times that for intact skin), whereas only a small (two-fold) increase was observed for poloid and hydrophilic poloid and the increase was negligible for white petrolatum and absorptive ointment. For skin without the stratum corneum, the ratio AUCskin/AUCplasma for the different ointments was comparable, although the magnitudes of AUCskin and AUCplasma still varied substantially. The variance of AUC values arises as a result of the different rates of release of salicylic acid from the bases. These results indicate that: the topical and transdermal delivery of salicylic acid in intact skin varies substantially among different ointment bases, and the greatest topical delivery is observed for absorptive ointment; use of absorptive ointment increases the

  12. Topical application of Gallic acid suppresses the 7,12-DMBA/Croton oil induced two-step skin carcinogenesis by modulating anti-oxidants and MMP-2/MMP-9 in Swiss albino mice.

    PubMed

    Subramanian, Vimala; Venkatesan, Balaji; Tumala, Anusha; Vellaichamy, Elangovan

    2014-04-01

    Gallic acid (GA - 3,4,5-trihydroxybenzoic acid), a dietary anti-oxidant has been shown to inhibit cancer cell growth in in vitro. Herein, we investigated the in vivo chemo preventive activity of GA on 7,12-Dimethylbenz[a]anthracene (DMBA)/Croton oil induced two-step skin carcinogenesis in Swiss albino mice. Skin tumor incidence and tumor volume were recorded during the 16 weeks of experimental period. In addition, LDH-isozyme shift, skin collagen content, activities of matrix metalloproteinases (MMP-2/MMP-9) enzymes and enzymatic and non-enzymatic antioxidant were studied in the skin and serum of experimental mice. Tumor incidence was significantly increased in the DMBA/Croton oil induced mice (100%; p<0.001) when compared to GA co-treated mice (60%; p<0.01) and 5-FU treated mice (50%; p<0.01). Skin collagen content, MMPs activities, LDH-isoenzymes and MMP-2/-9 expressions were increased in DMBA/Croton oil induced skin while decreased levels of enzymatic (GST, SOD, CAT & GPx) and non-enzymatic anti-oxidant (GSH) were noticed. On the other hand, GA co-treatment exhibited a significant protection by reverting back the altered levels of LDH-isoenzymes, antioxidants, collagen and MMP-2/MMP-9 activities. The results of this study indicate that topical application of GA inhibits DMBA/Croton oil induced two-stage skin carcinogenic process by modulating the antioxidants and MMPs (-2 & -9) in the mouse skin.

  13. Metabolic activation of chrysene in mouse skin: evidence for the involvement of a triol-epoxide.

    PubMed

    Hodgson, R M; Weston, A; Grover, P L

    1983-12-01

    All three possible dihydrodiols of chrysene and a chrysene triol, formed from the further metabolism of the chrysene-1,2-diol, were detected when ether extracts of mouse skin that had been treated with 3H-labelled chrysene were examined by h.p.l.c. The major deoxyribonucleoside-hydrocarbon adducts present in hydrolysates of DNA isolated from the mouse skin were examined by chromatography on Sephadex LH20 and by h.p.l.c. on Zorbax ODS. One adduct had chromatographic properties identical to those of the major adduct formed when r-1,t-2-dihydroxy-t-3,4-oxy-1,2,3,4-tetrahydrochrysene reacts with DNA. A second major adduct was present that had chromatographic properties that were indistinguishable from those of an adduct that was formed when either chrysene-1,2-diol or 3-hydroxychrysene were incubated with DNA in a rat liver microsomal metabolising system. The results provide evidence that this new adduct is formed via the reaction of a 'triol-epoxide', that appears to be 9-hydroxy-chrysene-1,2-diol 3,4-oxide, with DNA in mouse skin.

  14. The effects of topical L-selenomethionine on protection against UVB-induced skin cancer when given before, during, and after UVB exposure

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous studies in mice have shown that topical L-selenomethionine (SeMet) can prevent UVB-induced skin cancer when applied continuously before, during, and after the radiation exposure. With topical application of SeMet, selenium levels were shown to increase in the skin and liver, as well as in t...

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

    PubMed

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

    1992-01-01

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

  16. Triple nanoemulsion potentiates the effects of topical treatments with microencapsulated retinol and modulates biological processes related to skin aging *

    PubMed Central

    Afornali, Alessandro; de Vecchi, Rodrigo; Stuart, Rodrigo Makowiecky; Dieamant, Gustavo; de Oliveira, Luciana Lima; Brohem, Carla Abdo; Feferman, Israel Henrique Stokfisz; Fabrício, Lincoln Helder Zambaldi; Lorencini, Márcio

    2013-01-01

    BACKGROUND The sum of environmental and genetic factors affects the appearance and function of the skin as it ages. The identification of molecular changes that take place during skin aging provides biomarkers and possible targets for therapeutic intervention. Retinoic acid in different formulations has emerged as an alternative to prevent and repair age-related skin damage. OBJECTIVES To understand the effects of different retinoid formulations on the expression of genes associated with biological processes that undergo changes during skin aging. METHODS Ex-vivo skin samples were treated topically with different retinoid formulations. The modulation of biological processes associated with skin aging was measured by Reverse Transcription quantitative PCR (RT-qPCR). RESULTS A formulation containing microencapsulated retinol and a blend of active ingredients prepared as a triple nanoemulsion provided the best results for the modulation of biological, process-related genes that are usually affected during skin aging. CONCLUSION This association proved to be therapeutically more effective than tretinoin or microencapsulated retinol used singly. PMID:24474102

  17. Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitis.

    PubMed

    Li, Mei; Hener, Pierre; Zhang, Zhikun; Kato, Shigeaki; Metzger, Daniel; Chambon, Pierre

    2006-08-01

    We have demonstrated that cytokine thymic stromal lymphopoietin (TSLP), whose expression is rapidly induced upon keratinocyte-selective ablation of retinoid X receptors (RXRs) -alpha and -beta in the mouse (RXRalphabeta(ep-/-) mice), plays a key role in initiating a skin and systemic atopic dermatitis-like phenotype. We show here that topical application of the physiologically active ligand [1alpha,25-(OH)(2)D(3); calcitriol] of the vitamin D receptor, or of its low-calcemic analog MC903 (calcipotriol; Dovonex), induces TSLP expression in epidermal keratinocytes, which results in an atopic dermatitis-like syndrome mimicking that seen in RXRalphabeta(ep-/-) mutants and transgenic mice overexpressing TSLP in keratinocytes. Furthermore, topical application of retinoic acid receptor RARgamma-selective agonist BMS961 also induces TSLP expression either on its own or synergistically with 1alpha,25-(OH)(2)D(3). Our data demonstrate that RXR/vitamin D receptor and RXR/retinoic acid receptor-gamma heterodimers and their ligands cell-autonomously control the expression of TSLP in epidermal keratinocytes of the mouse. We propose molecular mechanisms through which vitamin D3 and retinoic acid signalings could be involved in the pathogenesis of atopic diseases.

  18. Topical gels of lidocaine HCl using cashew gum and Carbopol 940: preparation and in vitro skin permeation.

    PubMed

    Das, Biswarup; Nayak, Amit Kumar; Nanda, Upendranath

    2013-11-01

    The present study was attempted to prepare novel topical gels of 4% lidocaine HCl using cashew gum and Carbopol 940. The prepared gels were evaluated for pH, viscosity, and in vitro skin permeation through excised porcine skin. The pH of these topical gels was found within the range of 5.98-6.06; whereas, the viscosity was found 4.58 × 10(6) to 4.88 × 10(6) cps. The in vitro skin permeation from these gels showed permeation flux range, 851.34 ± 9.16 to 1568.15 ± 14.03 μg/cm(2)/h. The highest permeation flux (1568.15 ± 14.03 μg/cm(2)/h) was observed, when 0.01% menthol was added, which was higher than that of the marketed 4% lidicaine HCl topical gel (1355.41 ± 10.92 μg/cm(2)/h). These topical gels found best-fit with Korsmeyer-Peppas model and almost the super case-II transport mechanism. The stability study revealed that these gels were physically stable without occurrence of syneresis.

  19. Differential carcinogenic effects of intraperitoneal initiation with 7,12-dimethylbenz(a)anthracene or urethane and topical promotion with 12-O-tetradecanoylphorbol-13-acetate in skin and internal tissues of female SENCAR and BALB/c mice

    SciTech Connect

    Ward, J.M.; Rehm, S.; Devor, D.; Hennings, H.; Wenk, M.L.

    1986-09-01

    Groups of female SENCAR or BALB/c mice were initiated once intraperitoneally with 300 ..mu..g/mouse of 7,12-dimethylbenz(a) anthracene (DMBA) or 20 mg/mouse of urethane at 7 weeks of age. Beginning one week later, mice received topically applied acetone or 12-O-tetradecanoylphorbol-13-acetate (TPA), once weekly, at 2.5 ..mu..g/mouse for weeks 1 through 6 and 1.25 ..mu..g/mouse for weeks 7 through 52. The skin lesions were evaluated clinically. A complete necropsy was performed on all mice at week 52. SENCAR mice exposed to DMBA/TPA and urethane/TPA had more skin tumors than SENCAR mice exposed to DMBA or urethane alone and more than BALB/c mice in any treatment group. Of all skin carcinomas diagnosed histologically in DMBA/TPA-exposed mice, less than one-third had been identified clinically while the mice were alive. Most of the carcinomas arose within papillomas. BALB/c mice developed more vascular and uterine tumors than did SENCAR mice injected with DMBA and more lung and vascular tumors than did SENCAR mice injected with urethane. TPA exposure after treatment with either initiator had no significant effect on internal tumor development in either SENCAR or BALB/c mice.

  20. Injury thresholds for topical-cream-coated skin of hairless guinea pigs (cavia porcellus) in the near-infrared region

    NASA Astrophysics Data System (ADS)

    Pocock, Ginger M.; Zohner, Justin J.; Stolarski, David J.; Buchanan, Kelvin C.; Jindra, Nichole M.; Figueroa, Manuel A.; Chavey, Lucas J.; Imholte, Michelle L.; Thomas, Robert J.; Rockwell, Benjamin A.

    2006-02-01

    The reflectance and absorption of the skin plays a vital role in determining how much radiation will be absorbed by human tissue. Any substance covering the skin would change the way radiation is reflected and absorbed and thus the extent of thermal injury. Hairless guinea pigs (cavia porcellus) in vivo were used to evaluate how the minimum visible lesion threshold for single-pulse laser exposure is changed with a topical agent applied to the skin. The ED 50 for visible lesions due to an Er: glass laser at 1540-nm with a pulse width of 50-ns was determined, and the results were compared with model predictions using a skin thermal model. The ED50 is compared with the damage threshold of skin coated with a highly absorbing topical cream at 1540 nm to determine its effect on damage pathology and threshold. The ED 50 for the guinea pig was then compared to similar studies using Yucatan minipigs and Yorkshire pigs at 1540-nm and nanosecond pulse duration. 1,2 The damage threshold at 24-hours of a Yorkshire pig for a 2.5-3.5-mm diameter beam for 100 ns was 3.2 Jcm -2; very similar to our ED 50 of 3.00 Jcm -2 for the hairless guinea pigs.

  1. Protective effect of topically applied polypeptide from Chlamys farreri against ultraviolet radiation-induced chronic skin damage in guinea pig

    NASA Astrophysics Data System (ADS)

    Chi, Mingliang; Cao, Pengli; Yu, Guoying; Zhu, Li; Wang, Yuejun; Wang, Chunbo

    2003-12-01

    Polypeptide from Chlamys farreri (PCF), a topical polypeptide isolated from Chlamys farreri, was used in this experiment aimed to investigate the photoprotective effect of PCF against chronic skin damage induced by ultraviolet A (UVA) and ultraviolet B (UVB) radiation. The chronic ultraviolet-irradiated guinea pig model was established, and visible changes in the skin including wrinkling, sagging and erythema were observed. Malondialdehyde (MDA) and antioxidant enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) in the dorsal skin were determined using biochemical methods. The results showed: (1) PCF (5 % and 20%) could greatly protect the dorsal skin of guinea pig against wrinkling, sagging and erythema induced by UV radiation in a concentration-dependent manner. (2) PCF could reduce MDA formation in the dorsal skin caused by UV irradiation, while increasing the activities of SOD and GSH-px. (3) The differences among the PCF groups and UV model group were significant ( P<0.05, P<0.01). These results indicated that topical application, of PCF provided broad solar UV spectrum photoprotection; and that the antioxidant property of PCF might play a role in photoprotection.

  2. From topical antidote against skin irritants to a novel counter-irritating and anti-inflammatory peptide

    SciTech Connect

    Brodsky, Berta; Erlanger-Rosengarten, Avigail; Proscura, Elena; Shapira, Elena; Wormser, Uri

    2008-06-15

    The primary purpose of the present study was to investigate the mechanism of the counter-irritating activity of topical iodine against skin lesions induced by chemical and thermal stimuli. The hypothesis that iodine exerts its activity by inducing an endogenous anti-inflammatory factor was confirmed by exposing guinea pig skin to heat stimulus followed by topical iodine treatment and skin extraction. Injection of the extract into naive guinea pigs reduced heat-induced irritation by 69%. The protective factor, identified as a new nonapeptide (histone H2A 36-44, H-Lys-Gly-Asn-Tyr-Ala-Glu-Arg-Ileu-Ala-OH), caused reduction of 40% in irritation score in heat-exposed guinea pigs. The murine analog (H-Lys-Gly-His-Tyr-Ala-Glu-Arg-Val-Gly-OH, termed IIIM1) reduced sulfur mustard (SM)-induced ear swelling at a dose-dependent bell-shape manner reaching peak activity of 1 mg/kg. Cultured keratinocytes transfected with the peptide were more resistant towards SM than the control cells. The peptide suppressed oxidative burst in activated neutrophils in a concentration-dependent manner. In addition, the peptide reduced glucose oxidase-induced skin edema in mice at a dose-dependent bell-shape manner. Apart from thermal and chemical-induced skin irritation this novel peptide might be of potential use in chronic dermal disorders such as psoriasis and pemphigus as well as non-dermal inflammatory diseases like multiple sclerosis, arthritis and colitis.

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

    PubMed

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

    2013-10-15

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

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

    PubMed

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

    2013-10-15

    Lewisite is a potent chemical warfare arsenical vesicant that can cause severe skin lesions. Today, lewisite exposure remains possible during demilitarization of old ammunitions and as a result of deliberate use. Although its cutaneous toxicity is not fully elucidated, a specific antidote exists, the British anti-lewisite (BAL, dimercaprol) but it is not without untoward effects. Analogs of BAL, less toxic, have been developed such as meso-2,3-dimercaptosuccinic acid (DMSA) and have been employed for the treatment of heavy metal poisoning. However, efficacy of DMSA against lewisite-induced skin lesions remains to be determined in comparison with BAL. We have thus evaluated in this study the therapeutic efficacy of BAL and DMSA in two administration modes against skin lesions induced by lewisite vapor on SKH-1 hairless mice. Our data demonstrate a strong protective efficacy of topical application of dimercapto-chelating agents in contrast to a subcutaneous administration 1h after lewisite exposure, with attenuation of wound size, necrosis and impairment of skin barrier function. The histological evaluation also confirms the efficacy of topical application by showing that treatments were effective in reversing lewisite-induced neutrophil infiltration. This protective effect was associated with an epidermal hyperplasia. However, for all the parameters studied, BAL was more effective than DMSA in reducing lewisite-induced skin injury. Together, these findings support the use of a topical form of dimercaprol-chelating agent against lewisite-induced skin lesion within the first hour after exposure to increase the therapeutic management and that BAL, despite its side-effects, should not be abandoned. PMID:23806213

  5. Highly persistent polycyclic aromatic hydrocarbon-DNA adducts in mouse skin: detection by 32P-postlabeling analysis.

    PubMed

    Randerath, E; Agrawal, H P; Reddy, M V; Randerath, K

    1983-08-01

    A 32P-postlabeling method for carcinogen-DNA adduct analysis recently developed in our laboratory was applied to skin DNA from mice treated topically with polycyclic aromatic hydrocarbons (PAHs). After application of 4 doses of 1.2 mumol each of benzo[alpha]pyrene (BP), 3-methylcholanthrene (MC) and 7,12-dimethylbenz[alpha]anthracene (DMBA), respectively, total covalent adduct binding in mouse skin DNA initially amounted to 1 adduct in 6.0 X 10(4) - 1.3 X 10(5) nucleotides. Four weeks after treatment, these levels had declined to 1 adduct in 1.4 X 10(6) - 2.7 X 10(6) nucleotides. Substantial removal of DNA adducts occurred during the first 2 weeks after carcinogen application while adducts remaining thereafter underwent little or no repair between 2 and 4 weeks after treatment. These results raise the possibility that the persistent adducts occupy specific genomic sites in quiescent cells where they may not be amenable to repair because of localized conformational alterations of DNA or shielding by associated proteins. PMID:6318965

  6. An Advertisement and Article Analysis of Skin Products and Topics in Popular Women’s Magazines: Implications for Skin Cancer Prevention

    PubMed Central

    Basch, Corey H.; Mongiovi, Jennifer; Hillyer, Grace Clarke; Fullwood, MD; Ethan, Danna; Hammond, Rodney

    2015-01-01

    Background: In the United States, skin cancer is the most commonly diagnosed cancer, with an estimated 5 million people treated per year and annual medical treatment expenditures that exceed 8 billion dollars. The purpose of this study was two-fold: 1) to enumerate the number of advertisements for skin products with and without Sun Protection Factor (SPF) and to further analyze the specific advertisements for sunblock to determine if models, when present, depict sun safe behaviors and 2) to enumerate the number of articles related to the skin for content. Both aims include an assessment for differences in age and in magazines targeting a Black or Latina population. Methods: The sample for this cross sectional study was comprised of 99 issues of 14 popular United States magazines marketed to women, four of which market to a Black or Latina audience. Results: There were 6,142 advertisements, of which 1,215 (19.8%, 95% CI: 18.8-20.8%) were related to skin products. Among the skin product advertisements, 1,145 (93.8%, 95% CI: 93.9-96.3%) depicted skin products without SPF. The majority of skin articles (91.2%, 95% CI: 91.7-100.0%), skin product advertisements (89.9%, 95% CI: 88.2-91.6%), and sunblock advertisements featuring models (were found in magazines aimed at the older (>24 yr) audience. Conclusion: Future research on this topic could focus on the extent to which images in these magazines translate into risky health behaviors, such as sun seeking, or excessive other harmful effects of UV radiation. PMID:26933645

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

    PubMed

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

    2011-06-01

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

  8. Increased susceptibility to Staphylococcus aureus colonization of the skin of the NOA mouse: a potentially useful animal model for evaluating antiseptic effects.

    PubMed

    Kondo, Taizo; Ohno, Hitoshi; Taguchi, Keisuke; Satode, Ryotaro; Kondo, Toshio; Shiomoto, Yasuhisa

    2006-01-01

    Isolation of bacteria from wet skin lesions was attempted using Naruto Research Institute Otsuka Atrichia (NOA) mice, which develop such lesions spontaneously at a high rate. As a result, Staphylococcus aureus was demonstrated to have colonized the wet skin lesions at high density. In addition, the isolated S. aureus was found to be similar to the strain of S. aureus thought to colonize the eczematous lesions seen in humans with atopic dermatitis. Furthermore, a survey of the S. aureus colonization status of NOA mice with no wet skin lesions confirmed colonization at higher density than in HR-1 mice as control, indicating that the skin of the NOA mouse has the novel characteristic of increased susceptibility to S. aureus colonization. Thus, by using changes in S. aureus counts as an index, the NOA mouse can be expected to serve as a useful animal model for evaluating the effects of topical antiseptics. The antiseptic effects of an ointment and a lotion containing chlorhexidine gluconate were confirmed using this animal model.

  9. Enhanced effectiveness of tocotrienol-based nano-emulsified system for topical delivery against skin carcinomas.

    PubMed

    Pham, Jimmy; Nayel, Amy; Hoang, Christina; Elbayoumi, Tamer

    2016-06-01

    The potent anti-proliferative and pro-apoptotic actions of tocotrienols (T3) against cancer, but not normal tissues, have been hampered by their limited systemic bioavailabilty. Recent expansive development of diverse nanoemulsion (NE) vehicles emphasized their vast potential to improve the effective dosing of different clinical and experimental drugs of lipophilic nature, such as T3. The emphasis of the present work is to develop a pharmaceutically scalable, low-energy nano-emulsification approach for optimized incorporation of T3-rich palm oil (Tocomin®), possessing anticancer activity as a potential cutaneous delivery platform for adjunctive therapy of skin carcinomas, either alone or in combination with other chemotherapeutic agents. Different Tocomin®-NEs, obtained with different homogenization strategies, were screened based on physicochemical uniformity (droplet size, charge and polydispersity) and subjected to stress physical stability testing, along with chemical content analysis (≥90% Tocomin® - incorporation efficiency). Adopted hybrid nano-emulsification of Tocomin®, correlated with highest preservation of DPPH-radical scavenging capacity of active T3 in prototype formulation, Tocomin®-NE, which effectively permeated diffusion cell membranes 4-folds higher than propyleneglycol (PG)-admixed Tocomin® control. Against two different cell models of human cutaneous carcinoma, Tocomin®-hybrid NE demonstrated significantly stronger cytotoxic profiles (p ≤ 0.01), visible in both concentration- and time- dependent manners, with at least 5-folds lower IC50 values, compared to those estimated for the closest Tocomin®-control. The proposed hybrid nano-emulsified formulation of Tocomin® provides simple and stable delivery platform, for effective topical application against keratinocyte tumors.

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

    PubMed

    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

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

    PubMed

    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

  12. Dose-Dependent Onset of Regenerative Program in Neutron Irradiated Mouse Skin

    PubMed Central

    Artibani, Mara; Kobos, Katarzyna; Colautti, Paolo; Negri, Rodolfo; Amendola, Roberto

    2011-01-01

    Background Tissue response to irradiation is not easily recapitulated by cell culture studies. The objective of this investigation was to characterize, the transcriptional response and the onset of regenerative processes in mouse skin irradiated with different doses of fast neutrons. Methodology/Principal Findings To monitor general response to irradiation and individual animal to animal variation, we performed gene and protein expression analysis with both pooled and individual mouse samples. A high-throughput gene expression analysis, by DNA oligonucleotide microarray was done with three months old C57Bl/6 mice irradiated with 0.2 and 1 Gy of mono-energetic 14 MeV neutron compared to sham irradiated controls. The results on 440 irradiation modulated genes, partially validated by quantitative real time RT-PCR, showed a dose-dependent up-regulation of a sub-class of keratin and keratin associated proteins, and members of the S100 family of Ca2+-binding proteins. Immunohistochemistry confirmed mRNA expression data enabled mapping of protein expression. Interestingly, proteins up-regulated in thickening epidermis: keratin 6 and S100A8 showed the most significant up-regulation and the least mouse-to-mouse variation following 0.2 Gy irradiation, in a concerted effort toward skin tissue regeneration. Conversely, mice irradiated at 1 Gy showed most evidence of apoptosis (Caspase-3 and TUNEL staining) and most 8-oxo-G accumulation at 24 h post-irradiation. Moreover, no cell proliferation accompanied 1 Gy exposure as shown by Ki67 immunohistochemistry. Conclusions/Significance The dose-dependent differential gene expression at the tissue level following in vivo exposure to neutron radiation is reminiscent of the onset of re-epithelialization and wound healing and depends on the proportion of cells carrying multiple chromosomal lesions in the entire tissue. Thus, this study presents in vivo evidence of a skin regenerative program exerted independently from DNA repair

  13. Determination of the radioprotective effects of topical applications of MEA, WR-2721, and N-acetylcysteine on murine skin

    SciTech Connect

    Verhey, L.J.; Sedlacek, R.

    1983-01-01

    Topical applications of MEA (beta-mercaptoethylamine or cysteamine), WR-2721 (S-2-(3-aminopropylamino)-ethylphosphorothioic acid), and N-acetylcysteine (NAC) were tested for their ability to protect the normal skin of the hind legs of mice against acute and late damage from single doses of /sup 137/Cs radiation. No significant protection was observed with either WR-2721 or NAC. MEA was shown to offer significant protection against acute skin damage in both buffered and unbuffered forms, but no significant protection against late contraction. The use of topical MEA on unanesthetized animals breathing carbogen (95% O2, 5% CO2) appears to give an enhanced level of radioprotection over that shown for anesthetized, air-breathing animals.

  14. Effect of UVB on hydrolysis of alpha-tocopherol acetate to alpha-tocopherol in mouse skin.

    PubMed

    Kramer-Stickland, K; Liebler, D C

    1998-08-01

    We have assessed the hydrolysis of alpha-tocopherol acetate (alpha-TAc) to the active antioxidant alpha-tocopherol (alpha-TH) in mouse epidermis and in supernatant from epidermal homogenates. Topically administered alpha-TH prevents UVB photocarcinogenesis in C3H mice, whereas alpha-TAc does not. Hydrolysis in skin was monitored in mice treated topically with deuterium labeled alpha-TAc (d3-alpha-TAc). Epidermal samples were isolated from mice and analyzed for endogenous (d0-alpha-TAc) and d3-alpha-TH by gas chromatography-mass spectrometry. Within 24 h, the levels of d3-alpha-TH increased up to 10-fold over endogenous d0-alpha-TH levels; however, in mice irradiated with UVB prior to the application of d3-alpha-TAc, levels of d3-alpha-TH increased up to 30-40-fold over endogenous d0-alpha-TH. This enhancement of alpha-TAc hydrolysis increased with increasing UVB dose. Prior UVB exposure may increase hydrolysis of alpha-TAc by increasing epidermal esterase activity. Nonspecific esterase activity was measured in the 2000 x g supernatant from epidermis of unirradiated and irradiated mice. Alpha-napthyl acetate, a nonspecific esterase substrate, was converted to alpha-napthol in supernatants from unirradiated mice. Hydrolysis to alpha-napthol increased approximately 3-fold in supernatants from irradiated mice. Hydrolysis of alpha-TAc to alpha-TH also occurred in supernatant from unirradiated mice, and this hydrolysis increased approximately 3-fold in supernatant from irradiated animals. These data indicate that nonspecific esterase activity was increased by UVB in the skin, that alpha-TAc is converted to alpha-TH in the homogenate fraction containing nonspecific esterase, and that UVB exposure modulates the metabolism of alpha-TAc to alpha-TH in vivo.

  15. Oral Supplementation with Cocoa Extract Reduces UVB-Induced Wrinkles in Hairless Mouse Skin.

    PubMed

    Kim, Jong-Eun; Song, Dasom; Kim, Junil; Choi, Jina; Kim, Jong Rhan; Yoon, Hyun-Sun; Bae, Jung-Soo; Han, Mira; Lee, Sein; Hong, Ji Sun; Song, Dayoung; Kim, Seong-Jin; Son, Myoung-Jin; Choi, Sang-Woon; Chung, Jin Ho; Kim, Tae-Aug; Lee, Ki Won

    2016-05-01

    Cacao beans contain various bioactive phytochemicals that could modify the pathogeneses of certain diseases. Here, we report that oral administration of cacao powder (CP) attenuates UVB-induced skin wrinkling by the regulation of genes involved in dermal matrix production and maintenance. Transcriptome analysis revealed that 788 genes are down- or upregulated in the CP supplemented group, compared with the UVB-irradiated mouse skin controls. Among the differentially expressed genes, cathepsin G and serpin B6c play important roles in UVB-induced skin wrinkle formation. Gene regulatory network analysis also identified several candidate regulators responsible for the protective effects of CP supplementation against UVB-induced skin damage. CP also elicited antiwrinkle effects via inhibition of UVB-induced matrix metalloproteinases-1 expression in both the human skin equivalent model and human dermal fibroblasts. Inhibition of UVB-induced activator protein-1 via CP supplementation is likely to affect the expression of matrix metalloproteinases-1. CP supplementation also downregulates the expression of cathepsin G in human dermal fibroblasts. 5-(3',4'-Dihydroxyphenyl)-γ-valerolactone, a major in vivo metabolite of CP, showed effects similar to CP supplementation. These results suggest that cacao extract may offer a protective effect against photoaging by inhibiting the breakdown of dermal matrix, which leads to an overall reduction in wrinkle formation. PMID:26854493

  16. Evaluation of the skin blanching of topically applied steroids using a chroma meter in animals.

    PubMed

    Ishii, Hiroshi; Fujino, Konomi; Todo, Hiroaki; Sugibayashi, Kenji

    2012-01-01

    We evaluated the utility of animal skins for determining the skin blanching of steroids. A Chroma Meter was used to determine the skin blanching of steroids. Hydrophilic creams containing clobetasol propionate (CP) or prednisolone (PS) were selected as model steroid formulations. Skin blanching, a*, was determined using a Chroma Meter after the application of 0.005, 0.01, 0.1, or 1.0% CP or PS hydrophilic cream to the back skin of guinea pigs and hairless rats for 24 h. The relationships between Δa*(6h) and the skin concentrations of the steroids were determined at 6 h after removal of the cream. Δa*(6h) was markedly decreased after the application of CP hydrophilic cream to guinea pigs, and a good linear relationship was observed between Δa*(6h) and skin concentration (r=0.98). In contrast, no relationship was observed between these parameters after the application of CP cream to the hairless rats. Although skin blanching was observed after PS cream application in guinea pigs, no relationship was observed between Δa*(6h) and skin concentration of PS in each animal. These results suggest that the skin blanching effect of CP in guinea pigs is greater than that of PS and that its blanching effect in guinea pigs was stronger than that in hairless rats. Guinea pigs were found to be a good animal model for determining the skin blanching produced by steroid creams. In addition, Chroma Meters can be effectively used in skin vasoconstrictive tests in guinea pigs.

  17. Topical treatment with coenzyme Q10‐containing formulas improves skin's Q10 level and provides antioxidative effects

    PubMed Central

    Achterberg, Volker; Smuda, Christoph; Mielke, Heiko; Sperling, Gabi; Dunckelmann, Katja; Vogelsang, Alexandra; Krüger, Andrea; Schwengler, Helge; Behtash, Mojgan; Kristof, Sonja; Diekmann, Heike; Eisenberg, Tanya; Berroth, Andreas; Hildebrand, Janosch; Siegner, Ralf; Winnefeld, Marc; Teuber, Frank; Fey, Sven; Möbius, Janne; Retzer, Dana; Burkhardt, Thorsten; Lüttke, Juliane; Blatt, Thomas

    2015-01-01

    Abstract Ubiquinone (coenzyme Q10, Q10) represents an endogenously synthesized lipid‐soluble antioxidant which is crucial for cellular energy production but is diminished with age and under the influence of external stress factors in human skin. Here, it is shown that topical Q10 treatment is beneficial with regard to effective Q10 replenishment, augmentation of cellular energy metabolism, and antioxidant effects. Application of Q10‐containing formulas significantly increased the levels of this quinone on the skin surface. In the deeper layers of the epidermis the ubiquinone level was significantly augmented indicating effective supplementation. Concurrent elevation of ubiquinol levels suggested metabolic transformation of ubiquinone resulting from increased energy metabolism. Incubation of cultured human keratinocytes with Q10 concentrations equivalent to treated skin showed a significant augmentation of energy metabolism. Moreover, the results demonstrated that stressed skin benefits from the topical Q10 treatment by reduction of free radicals and an increase in antioxidant capacity. © 2015 BioFactors, 41(6):383–390, 2015 PMID:26648450

  18. Photodynamic therapy of non melanoma skin cancer murine model by topical application of a novel mTHPC liposomal formulation

    NASA Astrophysics Data System (ADS)

    Alexandratou, E.; Kyriazi, M.; Trebst, T.; Gräfe, S.; Yova, D.

    2007-07-01

    Photodynamic therapy (PDT) has been used in the treatment of various skin diseases including non melanoma skin carcinomas (NMSC). However, until now there are no publications concerning the efficacy of PDT after topical application of mTHPC. Although topical photosensitizer application presents many advantages over systemic drug administration, ALA-induced protoporphyrin IX is the only sensitizer topically used so far. In the present study photodynamic efficacy of the highly potent sensitizer meso-tetra(hydroxyphenyl)chlorin (mTHPC), supplied in a novel liposome formulation is investigated after topical application in hairless SKH-HR1 mice, bearing non melanoma skin carcinomas. The drug was applied topically for drug - light interval of 4 hours. The fluence rates were 100 and 50 mW/cm2 and two total energy doses, 10 J/cm2 and 100 J/cm2 were studied in groups of 5 animals. Three PDT sessions were performed in each animal, once every 7 days. The final evaluation of PDT effects was performed 14 days after the 3rd PDT treatment by measuring the geometrical characteristics of tumors. The groups treated with 100 mW/cm2 presented a higher complete tumor remission than the group of 50 mW/cm2 but an unusual high mortality. In the group of 50 mW/cm2 and 100 J/cm2, although the complete tumor remission percentage is poor, the tumor growth rate was decreased. No lesion, papilloma, or tumor was observed in the treated area even six months after tumor remission. Furthermore tumours up to 7 mm were achieved to be treated, indicating that this novel mTHPC formulation could be used for deeper and not only superficial carcinomas or lesions.

  19. Combined optical coherence tomography based on the extended Huygens-Fresnel principle and histology of mouse skin

    NASA Astrophysics Data System (ADS)

    Wu, Shulian; Li, Zhifang; Li, Hui; Shi, Xianghua

    2010-02-01

    Noninvasive measurement technique to obtain tissue optical properties such as the scattering coefficient μs and the anisotropy factor g using optical coherence tomography (OCT) scattering model which based on the Extended Huygens-Fresnel principle is developed in our paper. Older and younger mouse-skin are as animal model to compare its scattering coefficient μs and the anisotropy factor g, the outcome shows that scattering coefficient μs is increased with the age of mouse-skin. Furthermore, we have made age's mouse-skin into H.E stain slices; the result of its morphology is consistent with the OCT imaging and OCT-EHF principle. All of that have provided the theoretical basis which to the research on photo-aging skin and photo-rejuvenation.

  20. Compressive viscoelasticity of freshly excised mouse skin is dependent on specimen thickness, strain level and rate.

    PubMed

    Wang, Yuxiang; Marshall, Kara L; Baba, Yoshichika; Lumpkin, Ellen A; Gerling, Gregory J

    2015-01-01

    Although the skin's mechanical properties are well characterized in tension, little work has been done in compression. Here, the viscoelastic properties of a population of mouse skin specimens (139 samples from 36 mice, aged 5 to 34 weeks) were characterized upon varying specimen thickness, as well as strain level and rate. Over the population, we observed the skin's viscoelasticity to be quite variable, yet found systematic correlation of residual stress ratio with skin thickness and strain, and of relaxation time constants with strain rates. In particular, as specimen thickness ranged from 211 to 671 μm, we observed significant variation in both quasi-linear viscoelasticity (QLV) parameters, the relaxation time constant (τ1 = 0.19 ± 0.10 s) and steady-state residual stress ratio (G∞ = 0.28 ± 0.13). Moreover, when τ1 was decoupled and fixed, we observed that G∞ positively correlated with skin thickness. Second, as steady-state stretch was increased (λ∞ from 0.22 to 0.81), we observed significant variation in both QLV parameters (τ1 = 0.26 ± 0.14 s, G∞ = 0.47 ± 0.17), and when τ1 was fixed, G∞ positively correlated with stretch level. Third, as strain rate was increased from 0.06 to 22.88 s-1, the median time constant τ1 varied from 1.90 to 0.31 s, and thereby negatively correlated with strain rate. These findings indicate that the natural range of specimen thickness, as well as experimental controls of compression level and rate, significantly influence measurements of skin viscoelasticity.

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

    PubMed

    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

  2. Anti-epidermal growth factor receptor skin toxicity: a matter of topical hydration.

    PubMed

    Ferrari, Daris; Codecà, Carla; Bocci, Barbara; Crepaldi, Francesca; Violati, Martina; Viale, Giulia; Careri, Carmela; Caldiera, Sarah; Bordin, Veronica; Luciani, Andrea; Zonato, Sabrina; Cassinelli, Gabriela; Foa, Paolo

    2016-02-01

    Skin toxicity is a frequent complication of anti-epidermal growth factor receptor therapy, which can be an obstacle in maintaining the dose intensity and may negatively impact on the clinical outcome of cancer patients. Skin lesions depend on the disruption of the keratinocyte development pathways and no treatment is clearly effective in resolving the cutaneous alterations frequently found during anti-epidermal growth factor receptor therapy. Among systemic treatments, oral tetracycline proved to be useful in preventing skin manifestations. We describe the case of a patient affected by metastatic colorectal cancer, for whom a combination of chemotherapy and cetuximab was used as second-line treatment. The patient developed a symptomatic papulopustular skin rash that disappeared completely after a twice-daily application of a hydrating and moisturizing cream, mainly consisting of a mixture of paraffin, silicone compounds, and macrogol. The marked cutaneous amelioration allowed the patient to continue cetuximab without any further symptoms and was associated with a partial radiological response.

  3. Effects of topical and oral vitamin E on pigmentation and skin cancer induced by ultraviolet irradiation in Skh:2 hairless mice.

    PubMed

    Burke, K E; Clive, J; Combs, G F; Commisso, J; Keen, C L; Nakamura, R M

    2000-01-01

    This study investigates whether supplementation with topical RRR-alpha-tocopherol (Eol), topical RRR-alpha-tocopheryl succinate, and oral RRR-alpha-tocopheryl acetate can reduce the incidence of acute and chronic damage to the skin (i.e., sunburn and pigmentation and skin cancer, respectively) induced by ultraviolet (UV) irradiation to mice. Groups of twenty Skh:2 female hairless pigmented mice were treated with 1) lotion vehicle, 2) 5% Eol lotion, 3) 5% topical RRR-alpha-tocopheryl succinate lotion, or 4) lotion vehicle and oral RRR-alpha-tocopheryl acetate. Within each group, 15 mice were exposed to 0.24 J/cm2 of UV-B radiation three times per week. The animals' weights and food intakes were monitored, and the vitamin E concentrations of skin, liver, and adipose tissue were measured to determine whether the topical Eol resulted in significant tissue levels. Skin pigmentation was scored, and the total number of clinically detectable skin tumors per animal was counted weekly. Results showed that the skin concentrations of Eol, as well as levels in the adipose tissue, were increased after topical application. Mice treated with each form of vitamin E showed no signs of toxicity and had significantly less acute and chronic skin damage induced by UV irradiation, as indicated by reduced inflammation and pigmentation and by later onset and lesser incidence of skin cancer.

  4. Phosphatidylcholine liposomes as carriers to improve topical ascorbic acid treatment of skin disorders

    PubMed Central

    Serrano, Gabriel; Almudéver, Patricia; Serrano, Juan-Manuel; Milara, Javier; Torrens, Ana; Expósito, Inmaculada; Cortijo, Julio

    2015-01-01

    Liposomes have been intensively investigated as carriers for different applications in dermatology and cosmetics. Ascorbic acid has potent antioxidant and anti-inflammatory properties preventing photodamage of keratinocytes; however, due to its instability and low skin penetration, an appropriate carrier is mandatory to obtain desirable efficacy. The present work investigates the ability of a specific ascorbate phosphatidylcholine (PC) liposome to overcome the barrier of the stratum corneum and deliver the active agent into the dermis to prevent photodamage. Abdominal skin from ten patients was used. Penetration of PC liposomes was tested ex vivo in whole skin, epidermis, and dermis by means of fluorescein and sodium ascorbate. Histology and Franz diffusion cells were used to monitor the percutaneous absorption. Ultraviolet (UV)-high performance liquid chromatography was used to analyze diffusion of sodium ascorbate through the different skin layers, while spectrofluorimetry and fluorescent microscopy were used for fluorescein monitoring. UVA/UVB irradiation of whole skin was applied to analyze the antioxidant capacity by Trolox assay and anti-inflammatory effects by tumor necrosis factor alpha and interleukin 1 beta enzyme-linked immunoassay. PC liposomal formulation improved skin penetration of fluorescein and ascorbate. Fluorescein PC liposomes showed better diffusion through epidermis than dermis while ascorbate liposomes showed better diffusion through the dermis than the epidermis. Ascorbate PC liposomes showed preventive antioxidant and anti-inflammatory properties on whole human skin irradiated with UVA/UVB. In summary, ascorbate PC liposomes penetrate through the epidermis and allow nonstable hydrophilic active ingredients reach epidermis and dermis preventing skin photodamage. PMID:26719718

  5. Influence of anatomical site and topical formulation on skin penetration of sunscreens.

    PubMed

    Benson, Heather Ae; Sarveiya, Vikram; Risk, Stacey; Roberts, Michael S

    2005-09-01

    Sunscreen products are widely used to protect the skin from sun-related damage. Previous studies have shown that some sunscreen chemicals are absorbed across the skin to the systemic circulation. The current study shows that absorption into the skin of sunscreen chemicals applied to the face is up to four times greater than that of the same product applied to the back. This has implications for the way sunscreen products are formulated and may allow the use of less potent products on the face compared with the rest of the body. The effect of formulation vehicles on the release and skin penetration of the common sunscreen agent benzophenone-3 (common name oxybenzone) was also assessed. Penetration of benzophenone-3 across excised human epidermis and high-density polyethylene (HDPE) membrane was measured using in vitro Franz-type diffusion cells. Penetration and epidermal retention was measured following application of infinite and finite (epidermis only) doses of benzophenone-3 in five vehicles: liquid paraffin, coconut oil, 50:50 ethanol:coconut oil, aqueous cream BP, and oily cream BP. Highest benzophenone-3 skin retention was observed for the ethanol:coconut oil combination. Maximal and minimal benzophenone-3 fluxes were observed from liquid paraffin and coconut oil, respectively. The alcohol-based vehicle exhibited low benzophenone-3 release from the vehicle but high skin penetration and retention.

  6. Influence of anatomical site and topical formulation on skin penetration of sunscreens

    PubMed Central

    Benson, Heather AE; Sarveiya, Vikram; Risk, Stacey; Roberts, Michael S

    2005-01-01

    Sunscreen products are widely used to protect the skin from sun-related damage. Previous studies have shown that some sunscreen chemicals are absorbed across the skin to the systemic circulation. The current study shows that absorption into the skin of sunscreen chemicals applied to the face is up to four times greater than that of the same product applied to the back. This has implications for the way sunscreen products are formulated and may allow the use of less potent products on the face compared with the rest of the body. The effect of formulation vehicles on the release and skin penetration of the common sunscreen agent benzophenone-3 (common name oxybenzone) was also assessed. Penetration of benzophenone-3 across excised human epidermis and high-density polyethylene (HDPE) membrane was measured using in vitro Franz-type diffusion cells. Penetration and epidermal retention was measured following application of infinite and finite (epidermis only) doses of benzophenone-3 in five vehicles: liquid paraffin, coconut oil, 50:50 ethanol:coconut oil, aqueous cream BP, and oily cream BP. Highest benzophenone-3 skin retention was observed for the ethanol:coconut oil combination. Maximal and minimal benzophenone-3 fluxes were observed from liquid paraffin and coconut oil, respectively. The alcohol-based vehicle exhibited low benzophenone-3 release from the vehicle but high skin penetration and retention. PMID:18360561

  7. Topical Formulation Containing Naringenin: Efficacy against Ultraviolet B Irradiation-Induced Skin Inflammation and Oxidative Stress in Mice.

    PubMed

    Martinez, Renata M; Pinho-Ribeiro, Felipe A; Steffen, Vinicius S; Silva, Thais C C; Caviglione, Carla V; Bottura, Carolina; Fonseca, Maria J V; Vicentini, Fabiana T M C; Vignoli, Josiane A; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rubia

    2016-01-01

    Naringenin (NGN) exhibits anti-inflammatory and antioxidant activities, but it remains undetermined its topical actions against ultraviolet B (UVB)-induced inflammation and oxidative stress in vivo. The purpose of this study was to evaluate the physicochemical and functional antioxidant stability of NGN containing formulations, and the effects of selected NGN containing formulation on UVB irradiation-induced skin inflammation and oxidative damage in hairless mice. NGN presented ferric reducing power, ability to scavenge 2,2'-azinobis (3-ethylbenzothiazoline- 6-sulfonic acid) (ABTS) and hydroxyl radical, and inhibited iron-independent and dependent lipid peroxidation. Among the three formulations containing NGN, only the F3 kept its physicochemical and functional stability over 180 days. Topical application of F3 in mice protected from UVB-induced skin damage by inhibiting edema and cytokine production (TNF-α, IL-1β, IL-6, and IL-10). Furthermore, F3 inhibited superoxide anion and lipid hydroperoxides production and maintained ferric reducing and ABTS scavenging abilities, catalase activity, and reduced glutathione levels. In addition, F3 maintained mRNA expression of cellular antioxidants glutathione peroxidase 1, glutathione reductase and transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), and induced mRNA expression of heme oxygenase-1. In conclusion, a formulation containing NGN may be a promising approach to protecting the skin from the deleterious effects of UVB irradiation. PMID:26741806

  8. Topical Formulation Containing Naringenin: Efficacy against Ultraviolet B Irradiation-Induced Skin Inflammation and Oxidative Stress in Mice.

    PubMed

    Martinez, Renata M; Pinho-Ribeiro, Felipe A; Steffen, Vinicius S; Silva, Thais C C; Caviglione, Carla V; Bottura, Carolina; Fonseca, Maria J V; Vicentini, Fabiana T M C; Vignoli, Josiane A; Baracat, Marcela M; Georgetti, Sandra R; Verri, Waldiceu A; Casagrande, Rubia

    2016-01-01

    Naringenin (NGN) exhibits anti-inflammatory and antioxidant activities, but it remains undetermined its topical actions against ultraviolet B (UVB)-induced inflammation and oxidative stress in vivo. The purpose of this study was to evaluate the physicochemical and functional antioxidant stability of NGN containing formulations, and the effects of selected NGN containing formulation on UVB irradiation-induced skin inflammation and oxidative damage in hairless mice. NGN presented ferric reducing power, ability to scavenge 2,2'-azinobis (3-ethylbenzothiazoline- 6-sulfonic acid) (ABTS) and hydroxyl radical, and inhibited iron-independent and dependent lipid peroxidation. Among the three formulations containing NGN, only the F3 kept its physicochemical and functional stability over 180 days. Topical application of F3 in mice protected from UVB-induced skin damage by inhibiting edema and cytokine production (TNF-α, IL-1β, IL-6, and IL-10). Furthermore, F3 inhibited superoxide anion and lipid hydroperoxides production and maintained ferric reducing and ABTS scavenging abilities, catalase activity, and reduced glutathione levels. In addition, F3 maintained mRNA expression of cellular antioxidants glutathione peroxidase 1, glutathione reductase and transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), and induced mRNA expression of heme oxygenase-1. In conclusion, a formulation containing NGN may be a promising approach to protecting the skin from the deleterious effects of UVB irradiation.

  9. Topical Formulation Containing Naringenin: Efficacy against Ultraviolet B Irradiation-Induced Skin Inflammation and Oxidative Stress in Mice

    PubMed Central

    Martinez, Renata M.; Pinho-Ribeiro, Felipe A.; Steffen, Vinicius S.; Silva, Thais C. C.; Caviglione, Carla V.; Bottura, Carolina; Fonseca, Maria J. V.; Vicentini, Fabiana T. M. C.; Vignoli, Josiane A.; Baracat, Marcela M.; Georgetti, Sandra R.; Verri, Waldiceu A.; Casagrande, Rubia

    2016-01-01

    Naringenin (NGN) exhibits anti-inflammatory and antioxidant activities, but it remains undetermined its topical actions against ultraviolet B (UVB)-induced inflammation and oxidative stress in vivo. The purpose of this study was to evaluate the physicochemical and functional antioxidant stability of NGN containing formulations, and the effects of selected NGN containing formulation on UVB irradiation-induced skin inflammation and oxidative damage in hairless mice. NGN presented ferric reducing power, ability to scavenge 2,2′-azinobis (3-ethylbenzothiazoline- 6-sulfonic acid) (ABTS) and hydroxyl radical, and inhibited iron-independent and dependent lipid peroxidation. Among the three formulations containing NGN, only the F3 kept its physicochemical and functional stability over 180 days. Topical application of F3 in mice protected from UVB-induced skin damage by inhibiting edema and cytokine production (TNF-α, IL-1β, IL-6, and IL-10). Furthermore, F3 inhibited superoxide anion and lipid hydroperoxides production and maintained ferric reducing and ABTS scavenging abilities, catalase activity, and reduced glutathione levels. In addition, F3 maintained mRNA expression of cellular antioxidants glutathione peroxidase 1, glutathione reductase and transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), and induced mRNA expression of heme oxygenase-1. In conclusion, a formulation containing NGN may be a promising approach to protecting the skin from the deleterious effects of UVB irradiation. PMID:26741806

  10. Nanostructured lipid carriers-based flurbiprofen gel after topical administration: acute skin irritation, pharmacodynamics, and percutaneous absorption mechanism.

    PubMed

    Song, Aihua; Su, Zhen; Li, Sanming; Han, Fei

    2015-01-01

    In order to assess the preliminary safety and effectiveness of nanostructured lipid carriers-based flurbiprofen gel (FP NLC-gel), the acute irritation test, in vivo pharmacodynamics evaluation and pharmacokinetic study were investigated after topical application. No dropsy and erythema were observed after continuous dosing 7 d of FP NLC-gel on the rabbit skin, and the xylene-induced ear drossy could be inhibited by FP NLC-gel at different dosages. The maximum concentration of FP in rats muscle was 2.03 μg/g and 1.55 μg/g after oral and topical administration, respectively. While the peak concentration in untreated muscle after topical administration was only 0.37 μg/mL. And at any time, following topical administration the mean muscle-plasma concentration ratio Cmuscle/CPlasma was obviously higher than that following oral administration. Results indicated that FP could directly penetrate into the subcutaneous muscle tissue from the administration site. Thus, the developed FP NLC-gel could be a safe and effective vehicle for topical delivery of FP.

  11. Antiherpes Activity and Skin/Mucosa Distribution of Flavonoids from Achyrocline satureioides Extract Incorporated into Topical Nanoemulsions.

    PubMed

    Bidone, Juliana; Argenta, Débora Fretes; Kratz, Jadel; Pettenuzzo, Letícia Ferreira; Horn, Ana Paula; Koester, Letícia Scherer; Bassani, Valquíria Linck; Simões, Claudia Maria Oliveira; Teixeira, Helder Ferreira

    2015-01-01

    This study investigated the inhibitory effects of Achyrocline satureioides extract (ASE) incorporated into a topical nanoemulsion on Herpes Simplex Virus type 1 (HSV-1/KOS strain) replication, as well as the distribution of the main ASE flavonoids (quercetin, luteolin, and 3-O-methylquercetin) in porcine skin and mucosa. The ASE-loaded nanoemulsion showed more pronounced effects against HSV-1 replication when compared to the ASE or pure quercetin, as determined by the viral plaque number reduction assay. All flavonoids were detected in the skin epidermis (2.2 µg/cm(2)) and the mucosa upper layers (3.0 µg/cm(2)) from ASE-loaded nanoemulsion until 8 h after topical application. A higher amount of flavonoids was detected when these tissues were impaired, especially in deeper mucosa layers (up to 7-fold). Flavonoids were detected in the receptor fluid only when the mucosa was injured. Such results were supported by confocal microscopy images. Overall, these findings suggest that the tested ASE-loaded nanoemulsion has potential to be used topically for herpes infections.

  12. Antiherpes Activity and Skin/Mucosa Distribution of Flavonoids from Achyrocline satureioides Extract Incorporated into Topical Nanoemulsions

    PubMed Central

    Bidone, Juliana; Argenta, Débora Fretes; Kratz, Jadel; Pettenuzzo, Letícia Ferreira; Horn, Ana Paula; Koester, Letícia Scherer; Bassani, Valquíria Linck; Simões, Claudia Maria Oliveira; Teixeira, Helder Ferreira

    2015-01-01

    This study investigated the inhibitory effects of Achyrocline satureioides extract (ASE) incorporated into a topical nanoemulsion on Herpes Simplex Virus type 1 (HSV-1/KOS strain) replication, as well as the distribution of the main ASE flavonoids (quercetin, luteolin, and 3-O-methylquercetin) in porcine skin and mucosa. The ASE-loaded nanoemulsion showed more pronounced effects against HSV-1 replication when compared to the ASE or pure quercetin, as determined by the viral plaque number reduction assay. All flavonoids were detected in the skin epidermis (2.2 µg/cm2) and the mucosa upper layers (3.0 µg/cm2) from ASE-loaded nanoemulsion until 8 h after topical application. A higher amount of flavonoids was detected when these tissues were impaired, especially in deeper mucosa layers (up to 7-fold). Flavonoids were detected in the receptor fluid only when the mucosa was injured. Such results were supported by confocal microscopy images. Overall, these findings suggest that the tested ASE-loaded nanoemulsion has potential to be used topically for herpes infections. PMID:26101767

  13. Antiherpes Activity and Skin/Mucosa Distribution of Flavonoids from Achyrocline satureioides Extract Incorporated into Topical Nanoemulsions.

    PubMed

    Bidone, Juliana; Argenta, Débora Fretes; Kratz, Jadel; Pettenuzzo, Letícia Ferreira; Horn, Ana Paula; Koester, Letícia Scherer; Bassani, Valquíria Linck; Simões, Claudia Maria Oliveira; Teixeira, Helder Ferreira

    2015-01-01

    This study investigated the inhibitory effects of Achyrocline satureioides extract (ASE) incorporated into a topical nanoemulsion on Herpes Simplex Virus type 1 (HSV-1/KOS strain) replication, as well as the distribution of the main ASE flavonoids (quercetin, luteolin, and 3-O-methylquercetin) in porcine skin and mucosa. The ASE-loaded nanoemulsion showed more pronounced effects against HSV-1 replication when compared to the ASE or pure quercetin, as determined by the viral plaque number reduction assay. All flavonoids were detected in the skin epidermis (2.2 µg/cm(2)) and the mucosa upper layers (3.0 µg/cm(2)) from ASE-loaded nanoemulsion until 8 h after topical application. A higher amount of flavonoids was detected when these tissues were impaired, especially in deeper mucosa layers (up to 7-fold). Flavonoids were detected in the receptor fluid only when the mucosa was injured. Such results were supported by confocal microscopy images. Overall, these findings suggest that the tested ASE-loaded nanoemulsion has potential to be used topically for herpes infections. PMID:26101767

  14. Skin penetration and kinetics of pristine fullerenes (C{sub 60}) topically exposed in industrial organic solvents

    SciTech Connect

    Xia, Xin R.; Monteiro-Riviere, Nancy A.; Riviere, Jim E.

    2010-01-01

    Pristine fullerenes (C{sub 60}) in different solvents will be used in many industrial and pharmaceutical manufacturing and derivatizing processes. This report explores the impact of solvents on skin penetration of C{sub 60} from different types of industrial solvents (toluene, cyclohexane, chloroform and mineral oil). Yorkshire weanling pigs (n = 3) were topically dosed with 500 muL of 200 mug/mL C{sub 60} in a given solvent for 24 h and re-dosed daily for 4 days to simulate the worst scenario in occupational exposures. The dose sites were tape-stripped and skin biopsies were taken after 26 tape-strips for quantitative analysis. When dosed in toluene, cyclohexane or chloroform, pristine fullerenes penetrated deeply into the stratum corneum, the primary barrier of skin. More C{sub 60} was detected in the stratum corneum when dosed in chloroform compared to toluene or cyclohexane. Fullerenes were not detected in the skin when dosed in mineral oil. This is the first direct evidence of solvent effects on the skin penetration of pristine fullerenes. The penetration of C{sub 60} into the stratum corneum was verified using isolated stratum corneum in vitro; the solvent effects on the stratum corneum absorption of C{sub 60} were consistent with those observed in vivo. In vitro flow-through diffusion cell experiments were conducted in pig skin and fullerenes were not detected in the receptor solutions by 24 h. The limit of detection was 0.001 mug/mL of fullerenes in 2 mL of the receptor solutions.

  15. Retinoic acid and mouse skin morphogenesis. II. Role of epidermal competence in hair glandular metaplasia.

    PubMed

    Viallet, J P; Dhouailly, D

    1994-11-01

    Retinoic acid (RA) has marked effects on mouse upper-lip skin morphogenesis, leading to the development of glomerular gland instead of hair vibrissa follicle, but does not apparently change the dorsal pelage hair developmental program. In order to test the hypothesis that an up-regulation of the beta retinoic acid nuclear receptor (RAR beta) may be implicated in the alteration of the dermal-epidermal interactions which occur during cutaneous appendage development, RA-treated and untreated skin explants, controls as well as heterotopic recombinants, were made among nasal, upper-lip, and dorsal mouse embryonic tissues. They were analyzed by in situ hybridization with RAR beta 35S-labeled probe after 48 hr of in vitro culture as well as by identification of the morphological phenotype of cutaneous appendages after 6 additional days of culture on the chick chorioallantoic membrane. The results show that only mesenchyme from the facial region can express the RAR beta gene either normally or after RA treatment, depending on its nasal or upper-lip origin. However, the RAR beta up-regulation is unrelated to hair glandular metaplasia, which depends both on a glandular bias of the upper-lip epidermis and on the weakening of hair follicle-inducing dermal properties. The latter occurs in both the upper-lip and dorsal dermis as a consequence of RA treatment.

  16. TOPICAL REVIEW: Climate change, ozone depletion and the impact on ultraviolet exposure of human skin

    NASA Astrophysics Data System (ADS)

    Diffey, Brian

    2004-01-01

    For 30 years there has been concern that anthropogenic damage to the Earth's stratospheric ozone layer will lead to an increase of solar ultraviolet (UV) radiation reaching the Earth's surface, with a consequent adverse impact on human health, especially to the skin. More recently, there has been an increased awareness of the interactions between ozone depletion and climate change (global warming), which could also impact on human exposure to terrestrial UV. The most serious effect of changing UV exposure of human skin is the potential rise in incidence of skin cancers. Risk estimates of this disease associated with ozone depletion suggest that an additional peak incidence of 5000 cases of skin cancer per year in the UK would occur around the mid-part of this century. Climate change, which is predicted to lead to an increased frequency of extreme temperature events and high summer temperatures, will become more frequent in the UK. This could impact on human UV exposure by encouraging people to spend more time in the sun. Whilst future social trends remain uncertain, it is likely that over this century behaviour associated with climate change, rather than ozone depletion, will be the largest determinant of sun exposure, and consequent impact on skin cancer, of the UK population.

  17. In vivo methods for the analysis of the penetration of topically applied substances in and through the skin barrier.

    PubMed

    Lademann, J; Meinke, M C; Schanzer, S; Richter, H; Darvin, M E; Haag, S F; Fluhr, J W; Weigmann, H-J; Sterry, W; Patzelt, A

    2012-12-01

    The efficacy of a drug is characterized by its action mechanism and its ability to pass the skin barrier. In this article, different methods are discussed, which permit this penetration process to be analysed non-invasively. Providing qualitative and quantitative information, tape stripping is one of the oldest procedures for penetration studies. Although single cell layers of corneocytes are removed from the skin surface, this procedure is considered as non-invasive and is applicable exclusively to the stratum corneum. Recently, optical and spectroscopic methods have been used to investigate the penetration process. Fluorescence-labelled drugs can be easily detected in the skin by laser scanning microscopy. This method has the disadvantage that the dye labelling changes the molecular structures of the drug and consequently might influence the penetration properties. The penetration process of non-fluorescent substances can be analysed by Raman spectroscopy, electron paramagnetic resonance, CARS and multiphoton microscopic measurements. Using these methods, the concentration of the topically applied formulations in different depths of the stratum corneum can be detected by moving the laser focus from the skin surface deeper into the stratum corneum. The advantages and disadvantages of these methods will be discussed in this article. PMID:22957937

  18. In vivo methods for the analysis of the penetration of topically applied substances in and through the skin barrier.

    PubMed

    Lademann, J; Meinke, M C; Schanzer, S; Richter, H; Darvin, M E; Haag, S F; Fluhr, J W; Weigmann, H-J; Sterry, W; Patzelt, A

    2012-12-01

    The efficacy of a drug is characterized by its action mechanism and its ability to pass the skin barrier. In this article, different methods are discussed, which permit this penetration process to be analysed non-invasively. Providing qualitative and quantitative information, tape stripping is one of the oldest procedures for penetration studies. Although single cell layers of corneocytes are removed from the skin surface, this procedure is considered as non-invasive and is applicable exclusively to the stratum corneum. Recently, optical and spectroscopic methods have been used to investigate the penetration process. Fluorescence-labelled drugs can be easily detected in the skin by laser scanning microscopy. This method has the disadvantage that the dye labelling changes the molecular structures of the drug and consequently might influence the penetration properties. The penetration process of non-fluorescent substances can be analysed by Raman spectroscopy, electron paramagnetic resonance, CARS and multiphoton microscopic measurements. Using these methods, the concentration of the topically applied formulations in different depths of the stratum corneum can be detected by moving the laser focus from the skin surface deeper into the stratum corneum. The advantages and disadvantages of these methods will be discussed in this article.

  19. A new option in the treatment of skin tears for the institutionalized resident: formulated 2-octylcyanoacrylate topical bandage.

    PubMed

    Milne, Catherine T; Corbett, Lisa Q

    2005-01-01

    Skin tears are a common phenomenon in elderly institutionalized adults (EIAs). Incidence ranges from 0.92 to 2.5 per person/year. Little supportive literature exists regarding optimal treatment with many regimens reported. A convenience sample of 20 patients with Payne-Martin Category II and III skin tears of less than 8 hours' duration were prospectively evaluated with the use of a formulated 2-octylcyanoacrylate topical bandage. Patients were followed weekly until the tear healed. Complete healing occurred with 1 application of 2-OTB in 90% (18/20) of study subjects; 5% (n = 1) reported transient mild pain (less than 15 seconds), and 90% (n = 19) reported no pain. There were no incidents of cellulitis or infection. Shower and bathing routines were not interrupted. Cost averaged less than $1 per application. Clinician time averaged 1.5 minutes per application. Clinicians reported high satisfaction because repeated dressing changes were eliminated.

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

    PubMed

    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.

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

    PubMed

    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

  2. Topical absorption and toxicity studies of jet fuel hydrocarbons in skin

    NASA Astrophysics Data System (ADS)

    Muhammad, Faqir

    Kerosene-based fuels have been used for many decades. Over 2 million military and civilian personnel each year are occupationally exposed to various jet fuel mixtures. Dermatitis is one of the major health concerns associated with these exposures. In the past, separate absorption and toxicity studies have been conducted to find the etiology of such skin disorders. There was a need for integrated absorption and toxicity studies to define the causative constituents of jet fuel responsible for skin irritation. The focus of this thesis was to study the percutaneous absorption and to identify the hydrocarbons (HC) causing irritation in jet fuels so that preventive measures could be taken in the future. The initial study was conducted to understand the possible mechanism for additive interactions on hydrocarbon absorption/disposition in silastic, porcine skin and isolated perfused porcine skin flap (IPPSF) models. The influence of JP-8 (100) additives (MDA, BHT, 8Q405) on the dermal kinetics of 14C-naphthalene and 14C/3H-dodecane as markers of HC absorption was evaluated. This study indicated that individual and combination of additives influenced marker disposition in different membranes. MDA was a significant suppressor while BHT was a significant enhancer of naphthalene absorption in IPPSF. The 8Q405 significantly reduced naphthalene content in dosed silastic and skin indicating a direct interaction between additive and marker HC. Similarly, the individual MDA and BHT significantly retained naphthalene in the stratum corneum of porcine skin, but the combination of both of these additives statistically decreased the marker retention in the stratum corneum suggesting a potential biological interaction. This study concluded that all components of a chemical mixture should be assessed since the effects of single components administered alone or as pairs may be confounded when all are present in the complete mixture. However, this study indicated that the marker HC

  3. Efficacy of topical treatment of pigmentation skin disorders with plant hydroquinone glucosides as assessed by quantitative color analysis.

    PubMed

    Clarys, P; Barel, A

    1998-06-01

    Hydroquinone is a well known reagent used in the treatment of pigmentation disorders. The instability of the quinones and the required active concentration make topical treatment rather difficult. We tested the efficacy of an ascorbate-phytohydroquinone complex that inhibits the synthesis of melanin and promotes the degradation of the existing melanin. Lentigo senile lesions were evaluated before and after 1 month of treatment. Objective skin color evaluation was performed instrumentally. After one month of treatment, a clear depigmentation of the macules was measured. None of the volunteers reported any side effects from the prolonged treatment with the hydroquinone containing product. PMID:9675352

  4. Multi-stage chemical carcinogenesis in mouse skin: Fundamentals and applications

    PubMed Central

    Abel, Erika L.; Angel, Joe M; Kiguchi, Kaoru; DiGiovanni, John

    2011-01-01

    For more than 60 years, the chemical induction of tumors in mouse skin has been used to study mechanisms of epithelial carcinogenesis and evaluate modifying factors. In the traditional two-stage skin carcinogenesis model, initiation is accomplished by the application of a subcarcinogenic dose of a carcinogen. Subsequently, tumor development is elicited by repeated treatment with a tumor promoting agent. The initiation protocol can be completed within 1–3 hours depending on the number of mice used, while the promotion phase requires twice weekly treatments (1–2 hours) and once weekly tumor palpation (1–2 hours) for the duration of the study. A highly reproducible papilloma burden is expected within 10–20 weeks with progression of a portion of the tumors to squamous cell carcinomas within 20–50 weeks. In contrast to complete skin carcinogenesis, the two-stage model allows for greater yield of premalignant lesions as well as separation of the initiation and promotion phases. PMID:19713956

  5. Green tea polyphenol induces caspase 14 in epidermal keratinocytes via MAPK pathways and reduces psoriasiform lesions in the flaky skin mouse model.

    PubMed

    Hsu, Stephen; Dickinson, Douglas; Borke, James; Walsh, Douglas S; Wood, Joseph; Qin, Haiyan; Winger, Julia; Pearl, Henna; Schuster, George; Bollag, Wendy B

    2007-08-01

    Psoriasiform lesions are characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes, accompanied by inflammation, leading to a disrupted skin barrier with an abnormal stratum corneum. The expression and proteolytic processing of caspase 14, a member of the caspase family which is associated with epithelial cell differentiation, planned cell death, and barrier formation, is altered in psoriatic epidermis. We recently reported that human psoriatic tissues lack normal expression of caspase 14 [J Dermatol Sci37 (2005) 61], and caspase 14 is induced by EGCG, a green tea polyphenol (GTP), in exponentially growing normal human epidermal keratinocytes (NHEK) [J Pharmacol Exp Ther315 (2005) 805]. This suggests that GTPs may have beneficial effects on psoriasiform lesions. The current study aimed to determine whether MAPK pathways are required for GTP-induced caspase 14 expression in NHEK and if GTPs can modulate the expression of pathological markers in the psoriasiform lesions that develop in the flaky skin mouse. The results indicate that the p38 and JNK MAPK pathways are required for EGCG-induced expression of caspase 14 in NHEK. Importantly, topical application of 0.5% GTPs significantly reduced the symptoms of epidermal pathology in the flaky skin mice, associated with efficient caspase 14 processing and reduction in proliferating cell nuclear antigen levels. This suggests that GTP-activated pathways may be potential targets for novel therapeutic approaches to the treatment of some psoriasiform skin disorders.

  6. 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

    PubMed Central

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

    2011-01-01

    Nordihydroguaiaretic acid (NDGA) is a phenolic antioxidant found in the leaves and twigs of the evergreen desert shrub, Larrea tridentata (Sesse and Moc. ex DC) Coville (creosote bush). It has a long history of traditional medicinal use by the Native Americans and Mexicans. The modulatory effects of topically applied NDGA was studied on acute inflammatory and oxidative stress responses in mouse skin induced by stage I tumor promoting agent, 12-O-tetradecanoylphorbol-13-acetate (TPA). Double TPA treatment adversely altered many of the marker responses of stage I skin tumor promotion cascade. Pretreatment of NDGA in TPA-treated mice mitigated cutaneous lipid peroxidation and inhibited production of hydrogen peroxide. NDGA treatment also restored reduced glutathione level and activities of antioxidant enzymes. Elevated activities of myeloperoxidase, xanthine oxidase and skin edema formation in TPA-treated mice were also lowered by NDGA indicating a restrained inflammatory response. Furthermore, results of histological study demonstrated inhibitory effect of NDGA on cellular inflammatory responses. This study provides a direct evidence of antioxidative and anti-inflammatory properties of NDGA against TPA-induced cutaneous inflammation and oxidative stress corroborating its chemopreventive potential against skin cancer. PMID:19861506

  7. Enhanced delivery of topically-applied formulations following skin pre-treatment with a hand-applied, plastic microneedle array.

    PubMed

    Duan, Dan; Moeckly, Craig; Gysbers, Jerry; Novak, Chris; Prochnow, Gayatri; Siebenaler, Kris; Albers, Leila; Hansen, Kris

    2011-09-01

    The purpose of this work is to characterize microchannels created by polymeric microneedles, applied by hand, and to demonstrate enhanced delivery of topically applied formulations of lidocaine hydrochloride and methylprednisolone sodium succinate (MPSS). 3M's Microstructured Transdermal System (MTS) arrays were applied to domestic swine to demonstrate reliability of penetration, depth of penetration and durability of the structures to repeat application and high force. Tissue levels of lidocaine and MPSS following topical application with and without microneedle pretreatment were determined by HPLC-MS analysis following digestion of biopsies. Almost all microneedles penetrate the stratum corneum upon hand force application. The depth of penetration varies from <100µm to nearly 150µm depending on the application force and the firmness of the underlying tissue. The arrays show excellent durability to repeated in-vivo application, with less than 5% of the structures evidencing even minimal tip bending after 16 applications. Under extreme force against a rigid surface, the microneedles bend but do not break. A lidocaine hydrochloride formulation applied topically in-vivo showed ~340% increase in local tissue levels when the MTS arrays were used to twice pre-treat the skin prior to applying the drug. Local delivery of a topically applied formulation of MPSS was over one order of magnitude higher when the application site was twice pre-treated with the MTS array. 3M's MTS array (marketed as 3M(TM) Microchannel Skin System) provides repeatable and robust penetration of the stratum corneum and epidermis and enhances delivery of some formulations such as lidocaine hydrochloride. PMID:21696356

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

    PubMed

    Ito, Shinobu; Itoga, Kazuyoshi; Yamato, Masayuki; Akamatsu, Hirohiko; Okano, Teruo

    2010-01-12

    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 CH(3)MDFDA (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.

  9. Improvement of skin optical clearing efficacy by topical treatment of glycerol at different temperatures

    NASA Astrophysics Data System (ADS)

    Deng, Zijian; Liu, Caihua; Tao, Wei; Zhu, Dan

    2011-01-01

    In the past decades, laser has been widely used in clinical diagnosis and cosmetic therapy. However, there is limitation for further usage in deeper tissue for high scattering property. Skin optical clearing technique, by introducing optical clearing agents (OCAs) into tissue, will have a potential impact on optical diagnosis and therapy. In this work, anhydrous glycerol at different temperatures of 4, 25, 32 and 45°C were applied respectively to in vitro porcine skin, and reflectance and transmittance spectra were then measured dynamically using a spectrometry combined with integrating sphere system. Further, reduced scattering coefficient and penetration depth were obtained. Results showed that, glycerol at different temperatures could induce the reduced scattering coefficient of in vitro skin to decrease and the penetration depth to increase. 4 and 25°C glycerol had similar effect, decreasing the scattering by 48.2% and 49.7%, and increasing penetration depth by 37.9% and 39.5%, respectively. However, 32 and 45°C glycerol treatment could decrease scattering by 61.6% and 76.6%, and increase penetration depth by 53.3% and 84.1%, respectively. In conclusion, glycerol at higher temperature can induce greater and faster skin optical clearing efficacy.

  10. Anti-epidermal growth factor receptor skin toxicity: a matter of topical hydration.

    PubMed

    Ferrari, Daris; Codecà, Carla; Bocci, Barbara; Crepaldi, Francesca; Violati, Martina; Viale, Giulia; Careri, Carmela; Caldiera, Sarah; Bordin, Veronica; Luciani, Andrea; Zonato, Sabrina; Cassinelli, Gabriela; Foa, Paolo

    2016-02-01

    Skin toxicity is a frequent complication of anti-epidermal growth factor receptor therapy, which can be an obstacle in maintaining the dose intensity and may negatively impact on the clinical outcome of cancer patients. Skin lesions depend on the disruption of the keratinocyte development pathways and no treatment is clearly effective in resolving the cutaneous alterations frequently found during anti-epidermal growth factor receptor therapy. Among systemic treatments, oral tetracycline proved to be useful in preventing skin manifestations. We describe the case of a patient affected by metastatic colorectal cancer, for whom a combination of chemotherapy and cetuximab was used as second-line treatment. The patient developed a symptomatic papulopustular skin rash that disappeared completely after a twice-daily application of a hydrating and moisturizing cream, mainly consisting of a mixture of paraffin, silicone compounds, and macrogol. The marked cutaneous amelioration allowed the patient to continue cetuximab without any further symptoms and was associated with a partial radiological response. PMID:26469836

  11. Efficacy of Topical Application of Emu Oil on Areola Skin Barrier in Breastfeeding Women.

    PubMed

    Zanardo, Vincenzo; Giarrizzo, David; Maiolo, Luigi; Straface, Gianluca

    2016-01-01

    Appropriate hydration and skin surface pH are of fundamental importance in preventing areola skin barrier damage and breastfeeding success. We studied the dermal effects of emu oil on areola skin soon after birth in 70 at-term breastfeeding mothers by noninvasive bioengineering method. Emu oil-based cream was found to be effective in improving stratum corneum hydration of breast areolae (mean ± standard deviation, from 56.9 ± 18.2 to 65.0 ± 17.2 conventional units, P < .003) and did not affect skin pH, temperature, or elasticity. The significant improvement in hydration values was more pronounced in the puerperae presenting with basal hydration in the lower quartiles (mean ± standard deviation, from 41.6 ± 17.2 to 59.6 ± 21.2 conventional units, P < .001). Further studies are warranted to confirm the long-term beneficial effects of this preparation in a very sensitive patient population. PMID:26080458

  12. Evaluation of a topical treatment for the relief of sensitive skin

    PubMed Central

    Heinicke, Ingrid R; Adams, Damian H; Barnes, Tanya M; Greive, Kerryn A

    2015-01-01

    Background Approximately, 50% of the population claim to have sensitive skin, which has created an important challenge for dermatologists and the cosmetic industry. This study evaluates the properties of QV Face Rescue Gel (Rescue Gel) that contains a combination of moisturizing and anti-irritant ingredients, and which is used to relieve the symptoms of sensitive facial skin. Methods The ability of Rescue Gel to induce collagen types I and III in cultured neonatal human foreskin fibroblasts compared to transforming growth factor beta 1, a known potent inducer of collagen types I and III, was measured using immunofluorescence staining. Furthermore, healthy volunteers were recruited to measure the potential for Rescue Gel to reduce erythema induced by solar-simulated ultraviolet radiation on the skin compared to 0.5% hydrocortisone cream (positive control) as well as it’s ability to decrease transepidermal water loss compared to baseline levels. In addition, the formulation was tested for its potential to be 1) nonstinging using a facial sting/discomfort assay performed on volunteers who reacted positively to lactic acid, 2) nonirritating as determined by repeat insult patch tests, and 3) noncomedogenic. Results Rescue Gel significantly induced collagen types I and III in cultured human foreskin fibroblasts similarly to transforming growth factor beta 1. In volunteers, Rescue Gel was shown to significantly reduce erythema induced by solar-simulated ultraviolet radiation similarly to 0.5% hydrocortisone, and to significantly reduce transepidermal water loss compared to baseline levels. Further, the formulation was found to be nonstinging, nonirritating, and noncomedogenic. No adverse events were observed. Conclusion In this study, Rescue Gel has been shown to exhibit properties that make it effective for use on sensitive or irritated facial skin, without exacerbation of the symptoms associated with sensitive skin. PMID:26251625

  13. Combined topical application of lotus and green tea improves facial skin surface parameters.

    PubMed

    Mahmood, Tariq; Akhtar, Naveed

    2013-04-01

    No study has yet determined the anti-wrinkle efficacy of green tea plus lotus in Asian subjects using skin image analysis technique. In this study, the efficacy of two cosmetic active formulations intended for the treatment of facial wrinkles (green tea and lotus extract) has been evaluated in healthy subjects using a non-invasive device, the Visioscan(®) VC, and software for surface evaluation of living skin (SELS). Thirty-three healthy Asian subjects, all men, were enrolled after consent in a placebo-controlled comparative study with a split face design. One group applied multiple emulsions with green tea. The second group applied multiple emulsions with lotus extract, while a third group applied a multiple emulsion with a combination of both extracts. In all three groups, active formulations were applied to one side of the face and the placebo to the other side, once daily over the 60-day treatment course. Non-invasive measurements were performed at baseline and on days 30 and 60. Interesting and significant improvements were observed for the treatment effects on skin roughness (SEr), scaliness (SEsc), smoothness (SEsm), and wrinkling (SEw). For example, a 49.99% improvement in skin smoothness (SEsm) from baseline value and -23.22% and perfection in facial wrinkles (SEw) substantiated that combined treatment is superior over single treatments. Green tea and lotus combined in multiple emulsions brought a superior synergistic anti-aging effect. We conclude that diverse anti-oxidant constituents in both plants have a potential influence on skin surface parameters, thus indicating these plants as the future of new anti-aging products.

  14. Green tea polyphenol (-)-epigallocatechin-3-gallate treatment to mouse skin prevents UVB-induced infiltration of leukocytes, depletion of antigen-presenting cells, and oxidative stress.

    PubMed

    Katiyar, S K; Mukhtar, H

    2001-05-01

    Ultraviolet (UV) radiation-induced infiltrating leukocytes, depletion of antigen-presenting cells, and oxidative stress in the skin play an important role in the induction of immune suppression and photocarcinogenesis. Earlier we have shown that topical application of polyphenols from green tea or its major chemopreventive constituent (-)-epigallocatechin-3-gallate (EGCG) prevents UV-B-induced immunosuppression in mice. To define the mechanism of prevention, we found that topical application of EGCG (3 mg/mouse/3 cm(2) of skin area) to C3H/HeN mice before a single dose of UV-B (90 mJ/cm(2)) exposure inhibited UV-B-induced infiltration of leukocytes, specifically the CD11b+ cell type, and myeloperoxidase activity, a marker of tissue infiltration of leukocytes. EGCG treatment was also found to prevent UV-B-induced depletion in the number of antigen-presenting cells when immunohistochemically detected as class II MHC+ Ia+ cells. UV-B-induced infiltrating cell production of H2O2 and nitric oxide (NO) was determined as a marker of oxidative stress. We found that pretreatment of EGCG decreased the number of UV-B-induced increases in H2O2-producing cells and inducible nitric oxide synthase-expressing cells and the production of H2O2 and NO in both epidermis and dermis at a UV-B-irradiated site. Together, these data suggest that prevention of UV-B-induced infiltrating leukocytes, antigen-presenting cells, and oxidative stress by EGCG treatment of mouse skin may be associated with the prevention of UV-B-induced immunosuppression and photocarcinogenesis.

  15. Modulations of critical cell cycle regulatory events during chemoprevention of ultraviolet B-mediated responses by resveratrol in SKH-1 hairless mouse skin.

    PubMed

    Reagan-Shaw, Shannon; Afaq, Farrukh; Aziz, Moammir Hasan; Ahmad, Nihal

    2004-07-01

    Multiple exposures to solar ultraviolet (UV) radiation cause critical damages that may lead to the development of several cutaneous disorders including skin cancer, the most frequently diagnosed malignancy in the USA. Therefore, efforts are needed to: (i) study the mechanism(s) of UV-mediated cutaneous damages, and (ii) design novel approaches for the management of skin cancer. 'Chemoprevention' via plant-based agents may be a useful approach for the management of neoplasia. Here, we evaluated the involvement of cell cycle regulatory molecules during resveratrol-mediated protection from multiple exposures of UVB (180 mJ/cm(2); on alternate days x 7 exposures) radiations in the SKH-1 hairless mouse skin. Resveratrol was topically applied on the skin of SKH-1 hairless mice at a dose of 10 micromol/mouse (in 0.2 ml acetone; 30 min prior to each UVB exposure). Studies were performed at 24 h following the last UVB exposure. Topical application of resveratrol resulted in significant decrease in UVB-induced bi-fold skin thickness, hyperplasia, and infiltration of leukocytes. The data from immunoblot and/or immunohistochemical analyses revealed that multiple exposure to UVB radiations causes significant upregulation in: (i) proliferating cell nuclear antigen (PCNA), a marker of cellular proliferation, and (ii) cyclin-dependent kinase (cdk)-2, -4 and -6, cyclin-D1, and cyclin-D2. Resveratrol treatment resulted in significant downregulation in UV-mediated increases in these critical cell cycle regulatory proteins. An interesting observation of this study was that resveratrol treatment resulted in a further stimulation of UVB-mediated increases in cyclin kinase inhibitor WAF1/p21 and tumor suppressor p53. Further, resveratrol was also found to cause significant decreases in UVB-mediated upregulation of: (i) the mitogen-activated protein kinase kinase, and (ii) the 42 kDa isotype of mitogen-activated protein kinase (MAPK). Thus, our data suggested that the antiproliferative

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

    PubMed

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

    2014-08-01

    There is evidence that space flight condition-induced biological damage is associated with increased oxidative stress and extracellular matrix (ECM) remodeling. To explore possible mechanisms, changes in gene expression profiles implicated in oxidative stress and in ECM remodeling in mouse skin were examined after space flight. The metabolic effects of space flight in skin tissues were also characterized. Space Shuttle Atlantis (STS-135) was launched at the Kennedy Space Center on a 13-day mission. Female C57BL/6 mice were flown in the STS-135 using animal enclosure modules (AEMs). Within 3-5 h after landing, the mice were euthanized and skin samples were harvested for gene array analysis and metabolic biochemical assays. Many genes responsible for regulating production and metabolism of reactive oxygen species (ROS) were significantly (p < 0.05) altered in the flight group, with fold changes >1.5 compared to AEM control. For ECM profile, several genes encoding matrix and metalloproteinases involved in ECM remodeling were significantly up-/down-regulated following space flight. To characterize the metabolic effects of space flight, global biochemical profiles were evaluated. Of 332 named biochemicals, 19 differed significantly (p < 0.05) between space flight skin samples and AEM ground controls, with 12 up-regulated and 7 down-regulated including altered amino acid, carbohydrate metabolism, cell signaling, and transmethylation pathways. Collectively, the data demonstrated that space flight condition leads to a shift in biological and metabolic homeostasis as the consequence of increased regulation in cellular antioxidants, ROS production, and tissue remodeling. This indicates that astronauts may be at increased risk for pathophysiologic damage or carcinogenesis in cutaneous tissue.

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

    PubMed

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

    2014-08-01

    There is evidence that space flight condition-induced biological damage is associated with increased oxidative stress and extracellular matrix (ECM) remodeling. To explore possible mechanisms, changes in gene expression profiles implicated in oxidative stress and in ECM remodeling in mouse skin were examined after space flight. The metabolic effects of space flight in skin tissues were also characterized. Space Shuttle Atlantis (STS-135) was launched at the Kennedy Space Center on a 13-day mission. Female C57BL/6 mice were flown in the STS-135 using animal enclosure modules (AEMs). Within 3-5 h after landing, the mice were euthanized and skin samples were harvested for gene array analysis and metabolic biochemical assays. Many genes responsible for regulating production and metabolism of reactive oxygen species (ROS) were significantly (p < 0.05) altered in the flight group, with fold changes >1.5 compared to AEM control. For ECM profile, several genes encoding matrix and metalloproteinases involved in ECM remodeling were significantly up-/down-regulated following space flight. To characterize the metabolic effects of space flight, global biochemical profiles were evaluated. Of 332 named biochemicals, 19 differed significantly (p < 0.05) between space flight skin samples and AEM ground controls, with 12 up-regulated and 7 down-regulated including altered amino acid, carbohydrate metabolism, cell signaling, and transmethylation pathways. Collectively, the data demonstrated that space flight condition leads to a shift in biological and metabolic homeostasis as the consequence of increased regulation in cellular antioxidants, ROS production, and tissue remodeling. This indicates that astronauts may be at increased risk for pathophysiologic damage or carcinogenesis in cutaneous tissue. PMID:24796731

  18. Compressive Viscoelasticity of Freshly Excised Mouse Skin Is Dependent on Specimen Thickness, Strain Level and Rate

    PubMed Central

    Wang, Yuxiang; Marshall, Kara L.; Baba, Yoshichika; Lumpkin, Ellen A.; Gerling, Gregory J.

    2015-01-01

    Although the skin’s mechanical properties are well characterized in tension, little work has been done in compression. Here, the viscoelastic properties of a population of mouse skin specimens (139 samples from 36 mice, aged 5 to 34 weeks) were characterized upon varying specimen thickness, as well as strain level and rate. Over the population, we observed the skin’s viscoelasticity to be quite variable, yet found systematic correlation of residual stress ratio with skin thickness and strain, and of relaxation time constants with strain rates. In particular, as specimen thickness ranged from 211 to 671 μm, we observed significant variation in both quasi-linear viscoelasticity (QLV) parameters, the relaxation time constant (τ1 = 0.19 ± 0.10 s) and steady-state residual stress ratio (G∞ = 0.28 ± 0.13). Moreover, when τ1 was decoupled and fixed, we observed that G∞ positively correlated with skin thickness. Second, as steady-state stretch was increased (λ∞ from 0.22 to 0.81), we observed significant variation in both QLV parameters (τ1 = 0.26 ± 0.14 s, G∞ = 0.47 ± 0.17), and when τ1 was fixed, G∞ positively correlated with stretch level. Third, as strain rate was increased from 0.06 to 22.88 s−1, the median time constant τ1 varied from 1.90 to 0.31 s, and thereby negatively correlated with strain rate. These findings indicate that the natural range of specimen thickness, as well as experimental controls of compression level and rate, significantly influence measurements of skin viscoelasticity. PMID:25803703

  19. Does topical minoxidil increase skin blood flow? A laser Doppler flowmetry study.

    PubMed

    de Boer, E M; Bezemer, P D; Bruynzeel, D P; Nieboer, C

    1988-01-01

    Cutaneous blood flow was measured by Laser Doppler Flowmetry after topical application of minoxidil lotion, in 9 healthy males with androgenetic alopecia, and other volunteers. No reaction in the cutaneous blood flow was seen after application of 2%, 5%, or placebo minoxidil lotion.

  20. In vivo multiphoton imaging of human skin: assessment of topical corticosteroid-induced epidermis atrophy and depigmentation

    NASA Astrophysics Data System (ADS)

    Ait El Madani, Hassan; Tancrède-Bohin, Emmanuelle; Bensussan, Armand; Colonna, Anne; Dupuy, Alain; Bagot, Martine; Pena, Ana-Maria

    2012-02-01

    Multiphoton microscopy has emerged in the past decade as a promising tool for noninvasive skin imaging. Our aim was to evaluate the potential of multiphoton microscopy to detect topical corticosteroids side effects within the epidermis and to provide new insights into their dynamics. Healthy volunteers were topically treated with clobetasol propionate on a small region of their forearms under overnight occlusion for three weeks. The treated region of each patient was investigated at D0, D7, D15, D22 (end of the treatment), and D60. Our study shows that multiphoton microscopy allows for the detection of corticoid-induced epidermis modifications: thinning of stratum corneum compactum and epidermis, decrease of keratinocytes size, and changes in their morphology from D7 to D22. We also show that multiphoton microscopy enables in vivo three-dimensional (3-D) quantitative assessment of melanin content. We observe that melanin density decreases during treatment and almost completely disappears at D22. Moreover, these alterations are reversible as they are no longer present at D60. Our study demonstrates that multiphoton microscopy is a convenient and powerful tool for noninvasive 3-D dynamical studies of skin integrity and pigmentation.

  1. Skin hydration in postmenopausal women: argan oil benefit with oral and/or topical use

    PubMed Central

    Boucetta, Kenza Qiraouani; Charrouf, Zoubida; Derouiche, Abdelfattah; Rahali, Younes

    2014-01-01

    The aim of this study The aim of this study was to evaluate the effect of daily consumption and/or application of argan oil on skin hydration in postmenopausal women. Material and methods Sixty postmenopausal women consumed butter during the stabilization period and were randomly divided into two groups for the intervention period: the treatment group absorbed alimentary argan oil (n = 30) and the control group olive oil (n = 30). Both groups applied cosmetic argan oil in the left volar forearm during a sixty days’ period. Evaluation of skin hydration, i.e. transepidermal water loss (TEWL) and water content of the epidermis (WCE) on both volar forearms of the two groups, were performed during three visits at D0, D30 and after sixty days (D60) of oils treatment. Results The consumption of argan oil has led to a significant decrease in TEWL (p = 0.023) and a significant increase in WCE (p = 0.001). The application of argan oil has led to a significant decrease in TEWL (p = 0.01) and a significant increase in WCE (p < 0.001). Conclusions Our findings suggest that the daily consumption and application of argan oil have improved the skin hydration by restoring the barrier function and maintaining the water-holding capacity. PMID:26327867

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

    SciTech Connect

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

    1982-02-01

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

  3. Carcinogenic and co-carcinogenic studies of thiram on mouse skin.

    PubMed

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

    1996-03-01

    Thiram (tetramethyl thiuram disulfide), a carbamate fungicide, is used in the rubber processing industry as an accelerator and vulcanizing agent. Previous studies evaluated the tumorigenic potential of thiram in rodents, but failed to provide conclusive results. In the present study the tumorigenic potential of thiram was evaluated in Swiss albino mice by a two-stage initiation-promotion protocol and a long-term in vivo bioassay for carcinogenicity. Results revealed that following tumour initiation with thiram and promotion with 12-O-tetradecanoyl phorbol 13-acetate, skin tumours developed, mostly at the site of treatment (dorsal skin) in single and multiple dose-initiated animals. Similarly, papillomatous growths were observed on the dorsal skin of the mice initiated with a single subcarcinogenic dose of dimethylbenzanthracene and promoted with thiram. Thiram failed to provoke tumorigenesis when tested as a complete carcinogen for up to 52 wk and thereafter the study was terminated due to increased mortality. It is concluded that thiram has both tumour initiating and tumour-promoting potential in both sexes of Swiss albino mice following topical exposure at the tested dose level.

  4. Percutaneous absorption of methylprednisolone aceponate following topical application of Advantan lotion on intact, inflamed and stripped skin of male volunteers.

    PubMed

    Günther, C; Kecskes, A; Staks, T; Täuber, U

    1998-01-01

    Six healthy, elderly volunteers received three topical treatments with Advantan lotion containing 0.1% of methylprednisolone aceponate (MPA, CAS 86401-95-8) on intact, inflamed and stripped skin in a consecutive fashion at weekly intervals. The lotion (O/W emulsion) containing 14C-MPA (specific radioactivity 1.8 MBq/mg MPA) was applied in an area dose of 5 mg lotion/cm2 on a marked area of 100 cm2 on the back for 24 h. Inflammation was caused by UV-B irradiation at 3 MED 6 h prior to the treatment with the test preparation. Removal of stratum corneum was performed by 20-fold adhesive tape stripping. The concentration of radioactivity was measured in the plasma and in the urine up to 7 days following each treatment. The concentration of radioactivity in the plasma did not exceed the limit of detection of 1.5 ng MPA Eq/ml at any time point. The percutaneous absorption was assessed from the cumulated excretion of radiolabelled substances in the urine corrected for biliary excretion. Less than 0.5% of the dose was percutaneously absorbed through intact skin and through inflamed skin. After removal of the penetration barrier ('stripping') the percutaneous absorption increased to 15.4 +/- 7.7% of the applied dose.

  5. Topical application of superoxide dismutase mediated by HIV-TAT peptide attenuates UVB-induced damages in human skin.

    PubMed

    Chen, Xiaochao; Liu, Shutao; Rao, Pingfan; Bradshaw, Jeremy; Weller, Richard

    2016-10-01

    The purpose of this study was to evaluate whether topical application of superoxide dismutase with cell penetrating peptide (HIV-TAT) could protect against skin damage induced by UVB irradiation in humans. The permeability through stratum corneum of large proteins linked to TAT peptide was firstly confirmed by confocal microscopy and tape stripping. Ten healthy volunteers with either Fitzpatrick skin type II or III were recruited in this clinical study. TAT-SOD (300units/cm(2)) and vehicle cream were applied on two symmetric areas of both inner upper arms 1h prior to UVB irradiation. After one hour of pretreatment, subjects received 10 incremental doses of UVB on pretreated areas. 24h later, erythema, blood flow and apoptotic cells were measured. Pretreatment with TAT-SOD 1h prior to UVB radiation promoted a mean minimal erythema dose (MED) increase of 36.6±18.4% (p=0.013<0.05. n=10) compared to vehicle control. The median blood flow values of all subjects following 2 and 3-MED of UVB were 107.8±51.0units and 239.5±88.0units respectively, which account for 26% and 25% decrease with respect to vehicle groups. These data suggest that TAT-SOD significantly suppresses UVB induced erythema formation and blood flow rise. Furthermore, pretreatment with TAT-SOD 1h prior to 2-MED of UVB irradiation reduced the apoptotic sunburn cell formation by 47.6±8.6% (p<0.0001) in all subjects. Evaluating results generated from all measurements, we conclude that topical application of TAT-SOD significantly attenuates UVB-induced skin damage in man. These biological effects of TAT-SOD are probably mediated via its free radical scavenging properties, clearly differentiating it from other physical sunscreen agents. PMID:27460952

  6. Topical application of superoxide dismutase mediated by HIV-TAT peptide attenuates UVB-induced damages in human skin.

    PubMed

    Chen, Xiaochao; Liu, Shutao; Rao, Pingfan; Bradshaw, Jeremy; Weller, Richard

    2016-10-01

    The purpose of this study was to evaluate whether topical application of superoxide dismutase with cell penetrating peptide (HIV-TAT) could protect against skin damage induced by UVB irradiation in humans. The permeability through stratum corneum of large proteins linked to TAT peptide was firstly confirmed by confocal microscopy and tape stripping. Ten healthy volunteers with either Fitzpatrick skin type II or III were recruited in this clinical study. TAT-SOD (300units/cm(2)) and vehicle cream were applied on two symmetric areas of both inner upper arms 1h prior to UVB irradiation. After one hour of pretreatment, subjects received 10 incremental doses of UVB on pretreated areas. 24h later, erythema, blood flow and apoptotic cells were measured. Pretreatment with TAT-SOD 1h prior to UVB radiation promoted a mean minimal erythema dose (MED) increase of 36.6±18.4% (p=0.013<0.05. n=10) compared to vehicle control. The median blood flow values of all subjects following 2 and 3-MED of UVB were 107.8±51.0units and 239.5±88.0units respectively, which account for 26% and 25% decrease with respect to vehicle groups. These data suggest that TAT-SOD significantly suppresses UVB induced erythema formation and blood flow rise. Furthermore, pretreatment with TAT-SOD 1h prior to 2-MED of UVB irradiation reduced the apoptotic sunburn cell formation by 47.6±8.6% (p<0.0001) in all subjects. Evaluating results generated from all measurements, we conclude that topical application of TAT-SOD significantly attenuates UVB-induced skin damage in man. These biological effects of TAT-SOD are probably mediated via its free radical scavenging properties, clearly differentiating it from other physical sunscreen agents.

  7. Design, Development and Characterization of Topical Microemulsions of 5-Fluorouracil for the Treatment of Non Melanoma Skin Cancer and its Precursor Lesions.

    PubMed

    Kumar, Sudhir; Sinha, Vivek Ranjan

    2015-01-01

    Treatment of non melanoma skin cancer and its precancerous skin lesions is associated with severe topical and systemic toxicity. So, it has become necessary to develop an efficient novel delivery system with less side effects and better patient compliance. Topical w/o microemulsion of 5-FU were prepared using sorbitan monooleate (Span 80), sorbitan trioleate (Span 85), polysorbate 80 (Tween 80), isopropyl alcohol (IPA) with different oils such as oleic acid, triacetin and isopropyl myristate (IPM). Evaluation tests of microemulsions like determination of thermodynamic stability, droplet size, viscosity, pH, conductivity and ex vivo release studies were performed. Spherical shape and Droplet size of microemulsion, which was around 100nm, was supported by Transmission electron microscopy. The lesser flux across skin for all microemulsion batches and higher skin retention of 5-FU loaded in microemulsion in comparison to topical 5-FU marketed cream resulted in better control over the drug release. Skin irritation studies on rats were performed to evaluate chronic toxicity of optimized microemulsion formulation on skin for 21 days and were compared with control group. Formalin (0.8%) was taken as standard irritant. Rat skin was observed for erythema and edema and the formulation was found safe for chronic use (p˃0.01). Histopathology studies showed the epidermal and dermal layers to be normal, showing the 5-FU microemulsion formulation to be safe for topical use. Better control of the drug release through skin can curtail topical and systemic toxicity which is supported by the skin irritation and histopathology studies. PMID:26343142

  8. Topical anaesthetic effects on skin vasculature with potential implications for laser treatment.

    PubMed

    Tollan, Clare Josephine; MacLaren, William; Mackay, Iain R

    2016-05-01

    Laser treatment of vascular lesions is affected by parameters including the diameter and depth of the vessels and flow within the vessels. Topical anaesthetics are in common use prior to laser treatment but may have effects on vessel parameters and, subsequently, the efficacy of laser treatment. Eleven patients with capillary vascular malformations were investigated for vessel diameter before and after elective application of a topical anaesthetic, Eutectic Mixture of Local Anaesthetics (EMLA) (AstraZeneca) or Ametop (S&N Health), prior to pulsed dye laser treatment. EMLA contains 2.5% lidocaine ad 2.5% prilocaine, and Ametop gel contains 4% tetracaine. Patients' capillary malformations were assessed using confocal laser scanning microscopy (CLSM) (Vivascope 1500 Mavig GmbH, Munich). Six of the 11 patients recruited had EMLA topical anaesthetic, and five had Ametop. Four hundred twenty-one diameters were measured. The mean vessel diameter was 50.87 μm. Previous laser treatments undergone by each patient were noted to exclude this as a confounding variable, and no significant difference was found between topical anaesthetic groups. Statistical calculations were made using GenStat and Minitab. There is no evidence that Ametop affects mean diameter (p value is 0.361). EMLA reduces the mean diameter of vessels (p = 0.002), with a 27% reduction in post-EMLA diameter. This study demonstrates that the use of EMLA cream has a statistically significant reduction vessel diameter. As it is known that vessel diameter is important for the response of laser treatment, the use of EMLA may affect outcome. PMID:26861976

  9. Topical anaesthetic effects on skin vasculature with potential implications for laser treatment.

    PubMed

    Tollan, Clare Josephine; MacLaren, William; Mackay, Iain R

    2016-05-01

    Laser treatment of vascular lesions is affected by parameters including the diameter and depth of the vessels and flow within the vessels. Topical anaesthetics are in common use prior to laser treatment but may have effects on vessel parameters and, subsequently, the efficacy of laser treatment. Eleven patients with capillary vascular malformations were investigated for vessel diameter before and after elective application of a topical anaesthetic, Eutectic Mixture of Local Anaesthetics (EMLA) (AstraZeneca) or Ametop (S&N Health), prior to pulsed dye laser treatment. EMLA contains 2.5% lidocaine ad 2.5% prilocaine, and Ametop gel contains 4% tetracaine. Patients' capillary malformations were assessed using confocal laser scanning microscopy (CLSM) (Vivascope 1500 Mavig GmbH, Munich). Six of the 11 patients recruited had EMLA topical anaesthetic, and five had Ametop. Four hundred twenty-one diameters were measured. The mean vessel diameter was 50.87 μm. Previous laser treatments undergone by each patient were noted to exclude this as a confounding variable, and no significant difference was found between topical anaesthetic groups. Statistical calculations were made using GenStat and Minitab. There is no evidence that Ametop affects mean diameter (p value is 0.361). EMLA reduces the mean diameter of vessels (p = 0.002), with a 27% reduction in post-EMLA diameter. This study demonstrates that the use of EMLA cream has a statistically significant reduction vessel diameter. As it is known that vessel diameter is important for the response of laser treatment, the use of EMLA may affect outcome.

  10. Pretreatment of photoaged forearm skin with topical tretinoin accelerates healing of full-thickness wounds.

    PubMed

    Popp, C; Kligman, A M; Stoudemayer, T J

    1995-01-01

    Pretreatment of skin with all-trans retinoic acid (tretinoin) has been shown to enhance wound healing. Previous studies have mainly used animal models to demonstrate this effect. We wanted to determine whether pretreatment could promote wound healing in severely photoaged dorsal forearm skin. Four elderly men with severely actinically damaged forearms were treated daily for 16 weeks. One arm was treated with 0.05-0.1% tretinoin cream (Retin A, Ortho), and the other with Purpose cream (Ortho) as a vehicle control. Four-millimetre punch biopsies were taken from both dorsal forearms prior to treatment. After 16 weeks, full-thickness 2-mm punch biopsies were taken from both sides. Serial photographs were taken, and healing of the wounds quantitatively assessed by image analysis. On the 11th day, the wounds were excised using a 4-mm biopsy punch. Biopsies were processed for light microscopy. After 16 weeks, the tretinoin-treated forearms showed moderate erythema and scaling. Polarized light photographs revealed multiple, red, vascularized foci and/or a diffuse network of small vessels. The histological effects were typical for tretinoin, i.e. compaction of the stratum corneum, epidermal acanthosis with correction of atypia, an increase in small vessels, and increased cellularity in the upper dermis. Purpose cream had no effect, either clinically or histologically. On the tretinoin-treated side, the wound areas were 35-37% smaller on days 1 and 4, and 47-50% smaller on days 6, 8, 11, compared with the controls. Clinically and histologically, reepithelialization occurred more rapidly. Thus tretinoin dramatically accelerated wound healing in photodamaged skin.

  11. Topical corticosteroid delivery into human skin using hydrofluoroalkane metered dose aerosol sprays.

    PubMed

    Reid, Monica L; Benaouda, Faiza; Khengar, Rajeshree; Jones, Stuart A; Brown, Marc B

    2013-08-16

    Drug loaded hydrofluoroalkane (HFA) sprays can generate effective pharmaceutical formulations, but a deeper understanding of the manner in which these dynamic systems drive the process of in situ semi-solid dosage form assembly is required. The aim of this study was to investigate the effect of the matrix assembly and composition on drug localisation in human skin. Comparing the characteristics of sprays constituting HFA 134a, ethanol (EtOH), poly(vinyl pyrrolidone) K90, isopropyl myristate (IPM), and poly(ethylene glycol) (PEG) demonstrated that the addition of non-volatile solvents acted to delay EtOH evaporation, control the degree of drug saturation (DS) and enhance the corticosteroid delivery from HFA spray formulations. In a dose matched skin penetration study the HFA sprays containing only EtOH as a co-solvent delivered 2.1 μg BMV (DS 13.5) into the tissue, adding IPM to the EtOH HFA delivered 4.03 μg BMV (DS 11.2), whist adding PEG to the EtOH HFA delivered 6.1 μg BMV (DS 0.3). Compared to commercial cream (delivering 0.91 μg BMV) the EtOH/PEG HFA spray deposited over 6 times (p<0.05) more drug into the skin. Post spray deposition characterisation of the semi-solid suggested that the superior performance of the EtOH/PEG HFA spray was a consequence of retarding EtOH evaporation and presenting the drug in an EtOH rich PEG residual phase, which promoted BMV passage through the SC and into epidermis.

  12. Topical alpha-tocopherol acetate in the bulk phase: eight years of experience in skin treatment.

    PubMed

    Panin, Giorgio; Strumia, Renata; Ursini, Fulvio

    2004-12-01

    Clinical practice in dermatology indicates that alpha-tocopherol acetate is beneficial in xerosis, hyperkeratosis, asteatotic eczema, atopic dermatitis, superficial burns, cutaneous ulcers, onychoschizia and, in general, skin diseases in which an inflammatory process is activated. The positive effect results from the combination of biological activity, the absence of adverse reactions, and the physical effect of the alpha-tocopherol acetate oil. The viscosity of this oil in bulk phase accounts for a remarkable moisturizing effect and minimization of transepidermal water loss. This effect combines well with the antioxidant capacity of alpha-tocopherol released from the ester, and the recently emerging effect on reprogramming of gene expression.

  13. Analyzing the miRNA-Gene Networks to Mine the Important miRNAs under Skin of Human and Mouse

    PubMed Central

    Gong, Husile

    2016-01-01

    Genetic networks provide new mechanistic insights into the diversity of species morphology. In this study, we have integrated the MGI, GEO, and miRNA database to analyze the genetic regulatory networks under morphology difference of integument of humans and mice. We found that the gene expression network in the skin is highly divergent between human and mouse. The GO term of secretion was highly enriched, and this category was specific in human compared to mouse. These secretion genes might be involved in eccrine system evolution in human. In addition, total 62,637 miRNA binding target sites were predicted in human integument genes (IGs), while 26,280 miRNA binding target sites were predicted in mouse IGs. The interactions between miRNAs and IGs in human are more complex than those in mouse. Furthermore, hsa-miR-548, mmu-miR-466, and mmu-miR-467 have an enormous number of targets on IGs, which both have the role of inhibition of host immunity response. The pattern of distribution on the chromosome of these three miRNAs families is very different. The interaction of miRNA/IGs has added the new dimension in traditional gene regulation networks of skin. Our results are generating new insights into the gene networks basis of skin difference between human and mouse.

  14. Analyzing the miRNA-Gene Networks to Mine the Important miRNAs under Skin of Human and Mouse

    PubMed Central

    Gong, Husile

    2016-01-01

    Genetic networks provide new mechanistic insights into the diversity of species morphology. In this study, we have integrated the MGI, GEO, and miRNA database to analyze the genetic regulatory networks under morphology difference of integument of humans and mice. We found that the gene expression network in the skin is highly divergent between human and mouse. The GO term of secretion was highly enriched, and this category was specific in human compared to mouse. These secretion genes might be involved in eccrine system evolution in human. In addition, total 62,637 miRNA binding target sites were predicted in human integument genes (IGs), while 26,280 miRNA binding target sites were predicted in mouse IGs. The interactions between miRNAs and IGs in human are more complex than those in mouse. Furthermore, hsa-miR-548, mmu-miR-466, and mmu-miR-467 have an enormous number of targets on IGs, which both have the role of inhibition of host immunity response. The pattern of distribution on the chromosome of these three miRNAs families is very different. The interaction of miRNA/IGs has added the new dimension in traditional gene regulation networks of skin. Our results are generating new insights into the gene networks basis of skin difference between human and mouse. PMID:27689084

  15. A comprehensive evidence-based review on the role of topicals and dressings in the management of skin scarring.

    PubMed

    Sidgwick, G P; McGeorge, D; Bayat, A

    2015-08-01

    Wound healing after dermal injury is an imperfect process, inevitably leading to scar formation as the skin re-establishes its integrity. The resulting scars have different characteristics to normal skin, ranging from fine-line asymptomatic scars to problematic scarring including hypertrophic and keloid scars. Scars appear as a different colour to the surrounding skin and can be flat, stretched, depressed or raised, manifesting a range of symptoms including inflammation, erythema, dryness and pruritus, which can result in significant psychosocial impact on patients and their quality of life. In this paper, a comprehensive literature review coupled with an analysis of levels of evidence (LOE) for each published treatment type was conducted. Topical treatments identified include imiquimod, mitomycin C and plant extracts such as onion extract, green tea, Aloe vera, vitamin E and D, applied to healing wounds, mature scar tissue or fibrotic scars following revision surgery, or in combination with other more established treatments such as steroid injections and silicone. In total, 39 articles were included, involving 1703 patients. There was limited clinical evidence to support their efficacy; the majority of articles (n = 23) were ranked as category 4 LOE, being of limited quality with individual flaws, including low patient numbers, poor randomisation, blinding, and short follow-up periods. As trials were performed in different settings, they were difficult to compare. In conclusion, there is an unmet clinical need for effective solutions to skin scarring, more robust long-term randomised trials and a consensus on a standardised treatment regime to address all aspects of scarring. PMID:26044054

  16. Probe depth matters in dermal microdialysis sampling of benzoic acid after topical application: an ex vivo study in human skin.

    PubMed

    Holmgaard, R; Benfeldt, E; Bangsgaard, N; Sorensen, J A; Brosen, K; Nielsen, F; Nielsen, J B

    2012-01-01

    Microdialysis (MD) in the skin - dermal microdialysis (DMD) - is a unique technique for sampling of topically as well as systemically administered drugs at the site of action, e.g. sampling of dermatological drug concentrations in the dermis. Debate has concerned the existence of a correlation between the depth of the sampling device - the probe - in the dermis and the amount of drug sampled following topical drug administration. This study evaluates the relation between probe depth and drug sampling using dermal DMD sampling ex vivo in human skin. We used superficial (<1 mm), intermediate (1-2 mm) and deep (>2 mm) positioning of the linear MD probe in the dermis of human abdominal skin, followed by topical application of 4 mg/ml of benzoic acid (BA) in skin chambers overlying the probes. Dialysate was sampled every hour for 12 h and analysed for BA content by high-performance liquid chromatography. Probe depth was measured by 20-MHz ultrasound scanning. The area under the time-versus-concentration curve (AUC) describes the drug exposure in the tissue during the experiment and is a relevant parameter to compare for the 3 dermal probe depths investigated. The AUC(0-12) were: superficial probes: 3,335 ± 1,094 μg·h/ml (mean ± SD); intermediate probes: 2,178 ± 1,068 μg·h/ml, and deep probes: 1,159 ± 306 μg·h/ml. AUC(0-12) sampled by the superficial probes was significantly higher than that of samples from the intermediate and deeply positioned probes (p value <0.05). There was a significant inverse correlation between probe depth and AUC(0-12) sampled by the same probe (p value <0.001, r(2) value = 0.5). The mean extrapolated lag-times (±SD) for the superficial probes were 0.8 ± 0.1 h, for the intermediate probes 1.7 ± 0.5 h, and for the deep probes 2.7 ± 0.5 h, which were all significantly different from each other (p value <0.05). In conclusion, this paper demonstrates that there is an inverse relationship between the depth of the probe in the dermis

  17. Probe depth matters in dermal microdialysis sampling of benzoic acid after topical application: an ex vivo study in human skin.

    PubMed

    Holmgaard, R; Benfeldt, E; Bangsgaard, N; Sorensen, J A; Brosen, K; Nielsen, F; Nielsen, J B

    2012-01-01

    Microdialysis (MD) in the skin - dermal microdialysis (DMD) - is a unique technique for sampling of topically as well as systemically administered drugs at the site of action, e.g. sampling of dermatological drug concentrations in the dermis. Debate has concerned the existence of a correlation between the depth of the sampling device - the probe - in the dermis and the amount of drug sampled following topical drug administration. This study evaluates the relation between probe depth and drug sampling using dermal DMD sampling ex vivo in human skin. We used superficial (<1 mm), intermediate (1-2 mm) and deep (>2 mm) positioning of the linear MD probe in the dermis of human abdominal skin, followed by topical application of 4 mg/ml of benzoic acid (BA) in skin chambers overlying the probes. Dialysate was sampled every hour for 12 h and analysed for BA content by high-performance liquid chromatography. Probe depth was measured by 20-MHz ultrasound scanning. The area under the time-versus-concentration curve (AUC) describes the drug exposure in the tissue during the experiment and is a relevant parameter to compare for the 3 dermal probe depths investigated. The AUC(0-12) were: superficial probes: 3,335 ± 1,094 μg·h/ml (mean ± SD); intermediate probes: 2,178 ± 1,068 μg·h/ml, and deep probes: 1,159 ± 306 μg·h/ml. AUC(0-12) sampled by the superficial probes was significantly higher than that of samples from the intermediate and deeply positioned probes (p value <0.05). There was a significant inverse correlation between probe depth and AUC(0-12) sampled by the same probe (p value <0.001, r(2) value = 0.5). The mean extrapolated lag-times (±SD) for the superficial probes were 0.8 ± 0.1 h, for the intermediate probes 1.7 ± 0.5 h, and for the deep probes 2.7 ± 0.5 h, which were all significantly different from each other (p value <0.05). In conclusion, this paper demonstrates that there is an inverse relationship between the depth of the probe in the dermis

  18. A comparison of techniques to assess skin blanching following the topical application of glucocorticoids.

    PubMed

    Noon, J P; Evans, C E; Haynes, W G; Webb, D J; Walker, B R

    1996-05-01

    Glucocorticoid-induced dermal blanching provides a useful research tool to study steroid potency and sensitivity. Conventional measurement of the intensity of blanching relies on subjective assessment by a trained observer using a visual score. Several objective techniques have recently been reported to detect skin blanching, but their sensitivity has not been compared previously with subjective visual recordings. In this report we aimed to establish whether objective methods offer sufficient sensitivity to be employed in epidemiological studies of glucocorticoid responsiveness. In healthy subjects we applied beclomethasone dipropionate at three concentrations (1, 10 and 100 micrograms/ml) under an occluded dressing overnight. The following morning we measured blanching using a visual score, laser Doppler velocimetry with the MBF 3D monitor (Moor Instruments Ltd, U.K.) and a perfusion imager (Lisca, Sweden), and reflectance spectrophotometry with the Dia-Stron 'erythemameter'. Using the visual score, blanching was detected at all concentrations of steroid. Neither laser Doppler instrument detected vasoconstriction at any concentration. By contrast, the reflectance spectrophotometer successfully recorded blanching at 10 and 100 micrograms/ml, but not at 1 microgram/ml. We conclude that laser Doppler instruments, including the novel scanning perfusion imager, do not detect glucocorticoid-induced skin blanching, perhaps because it reflects venular rather than arteriolar vasoconstriction. By contrast, the Dia-Stron reflectance spectrophotometer has sufficient sensitivity to be used as an alternative to visual assessment in epidemiological studies of human glucocorticoid-induced dermal blanching.

  19. Epidermal hyperplasia in mouse skin following treatment with alternative drinking water disinfectants

    SciTech Connect

    Robinson, M.; Bull, R.J.; Schamer, M.; Long, R.E.

    1986-11-01

    Female SENCAR mice were treated with aqueous solutions of hypochlorous acid (HOCl), sodium hypochlorite (NaOCl), chlorine dioxide (ClO/sub 2/), and monochloramine (NH/sub 2/Cl) by whole body exposure (except head) for a 10-min period for 4 days in the first experiment and for 1 day (except NH/sub 2/Cl) in the second experiment. Animals were sacrificed the day following the last treatment (experiment 1) or on day 1, 2, 3, 4, 5, 8, 10, and 12 following treatment (experiment 2), and skin thickness was measured by light microscopy. Concentrations of disinfectants were 1, 10, 100, 300, and 1000 mg/L, for experiment 1 and 1000 mg/L for experiment 2. Thickness of the interfollicular epidermis (IFE) for control animals was 15.4 +/- 1.5 ..mu..m. After 4 days of treatment at 1000 mg/L, HOCl and ClO/sub 2/ increased thickness to 30 +/- 7.0 and 40.2 +/- 11.8, and NaOCl increased thickness to 25.2 +/- 6.1 ..mu.. m. The response to HOCl was found to be dose-related. The time-course study following a single treatment of 1000 mg/L HOCl, showed a progression of IFE thickening of from 18.3 +/- 1.4 at 1 day to 30.8 +/- 8.0 at 8 days, decreasing to 19.1 +/- 6.2 ..mu..m at 12 days. ClO/sub 2/ and NaOCl when tested in this manner did not produce increased thickness of IFE with time, but rather gave a persistent level of increase that remained for the 12 days. NH/sub 2/Cl reduced skin thickness to 13.6 +/- 6.1 ..mu..m. Examination of sections of skin treated with HOCl and ClO/sub 2/ indicated an increase in cell numbers. HOCl and ClO/sub 2/ are therefore capable of inducting hyperplastic responses in the mouse skin. The basis for the decrease in skin thickness resulting from NH/sub 2/Cl treatment remains to be established.

  20. Skin cancer treatment by albumin/5-Fu loaded magnetic nanocomposite spheres in a mouse model.

    PubMed

    Misak, H; Zacharias, N; Song, Z; Hwang, S; Man, K-P; Asmatulu, R; Yang, S-Y

    2013-03-10

    Albumin/drug loaded magnetic nanocomposite spheres were fabricated using an oil-in-oil emulsion/solvent evaporation method, and tested on a mouse model (experimental squamous cell carcinoma) to determine the efficacy of the drug delivery system (DDS) on skin cancer. This novel DDS consists of human serum albumin, poly(lactic-co-glycolic acid) (PLGA), 5-fluorouracil (5-Fu), magnetic nanoparticles (10 nm) and fluorescent labeling molecule (diphenylhexatriene). One of the major purposes of using albumin is that it likely provides internal binding to and retention by the inflammatory tissues to reduce the amount of magnetic nanoparticles needed in the drug loaded microspheres (750–1100 nm). This study is aimed at reducing many negative side effects of conventionally used chemotherapy drugs by localizing the chemotherapy drug, controlling the release of the therapeutic agent and encouraging uptake of the DDS into cancerous cells. A group of mice treated with (1) the magnetic targeted DDS were compared to the other three groups, including, (2) DDS without a magnet, (3) 5-Fu local injection, and (4) untreated groups. The fluorescent tracer was ubiquitously identified inside the tumor tissue, and the DDS/tumor tissue boundary presented a leaky interface. The test results clearly showed that the magnetic targeted DDS exhibited significantly superior therapeutic effects in treating the skin cancer, with the increased efficacy to halt the tumor growth. PMID:23395619

  1. A method to visualize transdermal nickel permeation in mouse skin using a nickel allergy patch

    PubMed Central

    Sugiyama, Tomoko; Uo, Motohiro; Wada, Takahiro; Hongo, Toshio; Omagari, Daisuke; Komiyama, Kazuo; Oikawa, Masakazu; Kusama, Mikio; Mori, Yoshiyuki

    2015-01-01

    Metal patch test is often used in clinical settings when metal-induced contact dermatitis is suspected. However, the transdermal permeation behavior of metal ions from the patch test remains unclear. Current patch tests using high concentrations of metal salt solutions have some side effects, e.g. acute skin reactions to high concentrations of metal salt. To resolve these, estimating metal ion transdermal permeation is wished. In this study, synchrotron radiation X-ray fluorescence (SR-XRF) and micro-focused particle-induced X-ray emission (micro-PIXE) were used to visualize the time-dependent Ni permeation in mouse skin. The cross-sectional diffusion of Ni was visualized in a time-dependent manner. Our results indicate that maximum Ni permeation occurs after 24 h of patch treatment, and the permeated Ni content was high in the epidermis and spread into the dermis beyond the basal layer. This method may be useful to determine the appropriate solution concentration and duration of administration for the patch test. PMID:26484550

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-11-01

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

  4. Inhibition of DNA and protein synthesis in UV-irradiated mouse skin by 2-difluoromethylornithine, methylglyoxal bis(guanylhydrazone), and their combination

    SciTech Connect

    Kaepyaho, K.; Lauharanta, J.; Jaenne, J.

    1983-08-01

    Exposure of mouse skin to UVB irradiation greatly enhanced the biosynthesis and accumulation of putrescine and spermidine before or concomitantly with stimulation of epidermal macromolecular (DNA and protein) synthesis. Topical treatment of UV-exposed skin with 2 inhibitors of polyamine biosynthesis, 2-difluoromethylornithine (DFMO) and methylglyoxal bis(guanylhydrazone) (MGBG) prevented the enhanced epidermal accumulation of polyamines, especially spermidine, and also inhibited the incorporation of radioactive precursors into DNA and protein. When applied in combination, these 2 antimetabolites of polyamines produced an inhibition of macromolecular synthesis that was at least additive: (/sup 3/H)thymidine incorporation decreased by 80% and (/sup 14/C)leucine incorporation by 44% as compared with the UVB-irradiated control mice. A slight decrease in the ratio of (/sup 3/H)histidine/(/sup 14/C)leucine incorporation indicated that protein synthesis of the differentiating cell layers was also affected by the inhibitors. The effects of the combined DFMO and MGBG treatment were partially reversed by concomitant topical application of spermidine.

  5. Pharmacological evaluation of a series of smoothened antagonists in signaling pathways and after topical application in a depilated mouse model.

    PubMed

    Lauressergues, Emilie; Heusler, Peter; Lestienne, Fabrice; Troulier, David; Rauly-Lestienne, Isabelle; Tourette, Amélie; Ailhaud, Marie-Christine; Cathala, Claudie; Tardif, Stéphanie; Denais-Laliève, Delphine; Calmettes, Marie-Thérèse; Degryse, Anne-Dominique; Dumoulin, Antoine; De Vries, Luc; Cussac, Didier

    2016-04-01

    The Hedgehog (HH) pathway has been linked to the formation of basal cell carcinoma (BCC), medulloblastoma, and other cancers. The recently approved orally active drugs vismodegib (GDC-0449) and sonidegib (LDE-225) were not only efficacious for the treatment of advanced or metastatic BCC by antagonizing the smoothened (SMO) receptor, but also produced important side effects, limiting their use for less invasive BCC. Herein, we compared a large series of SMO antagonists, including GDC-0449 and LDE-225, the clinically tested BMS-833923, CUR-61414, cyclopamine, IPI-926 (saridegib), itraconazole, LEQ-506, LY-2940680 (taladegib), PF-04449913 (glasdegib), and TAK-441 as well as preclinical candidates (PF-5274857, MRT-83) in two SMO-dependent cellular assays and for G-protein activation. We report marked differences in inhibitor potencies between compounds as well as a notable disparity between the G-protein assay and the cellular tests, suggesting that classification of drugs is assay dependent. Furthermore, we explored topical efficacies of SMO antagonists on depilated mice using Gli1 and Ptch1 mRNA quantification in skin as biomarkers of the HH signaling inhibition. This topical model rapidly discriminated drugs in terms of efficacies and potencies for inhibition of both biomarkers. SMO antagonists showed also a large variation in their blood and skin partition, suggesting that some drugs are more favorable for topical application. Overall, our data suggested that in vitro and in vivo efficacious drugs such as LEQ-506 and TAK-441 may be of interest for topical treatment of less invasive BCC with minimal side effects.

  6. Pharmacological evaluation of a series of smoothened antagonists in signaling pathways and after topical application in a depilated mouse model.

    PubMed

    Lauressergues, Emilie; Heusler, Peter; Lestienne, Fabrice; Troulier, David; Rauly-Lestienne, Isabelle; Tourette, Amélie; Ailhaud, Marie-Christine; Cathala, Claudie; Tardif, Stéphanie; Denais-Laliève, Delphine; Calmettes, Marie-Thérèse; Degryse, Anne-Dominique; Dumoulin, Antoine; De Vries, Luc; Cussac, Didier

    2016-04-01

    The Hedgehog (HH) pathway has been linked to the formation of basal cell carcinoma (BCC), medulloblastoma, and other cancers. The recently approved orally active drugs vismodegib (GDC-0449) and sonidegib (LDE-225) were not only efficacious for the treatment of advanced or metastatic BCC by antagonizing the smoothened (SMO) receptor, but also produced important side effects, limiting their use for less invasive BCC. Herein, we compared a large series of SMO antagonists, including GDC-0449 and LDE-225, the clinically tested BMS-833923, CUR-61414, cyclopamine, IPI-926 (saridegib), itraconazole, LEQ-506, LY-2940680 (taladegib), PF-04449913 (glasdegib), and TAK-441 as well as preclinical candidates (PF-5274857, MRT-83) in two SMO-dependent cellular assays and for G-protein activation. We report marked differences in inhibitor potencies between compounds as well as a notable disparity between the G-protein assay and the cellular tests, suggesting that classification of drugs is assay dependent. Furthermore, we explored topical efficacies of SMO antagonists on depilated mice using Gli1 and Ptch1 mRNA quantification in skin as biomarkers of the HH signaling inhibition. This topical model rapidly discriminated drugs in terms of efficacies and potencies for inhibition of both biomarkers. SMO antagonists showed also a large variation in their blood and skin partition, suggesting that some drugs are more favorable for topical application. Overall, our data suggested that in vitro and in vivo efficacious drugs such as LEQ-506 and TAK-441 may be of interest for topical treatment of less invasive BCC with minimal side effects. PMID:27069629

  7. Evaluation of changes in the haemoglobin of skin and muscle tissue of the calf, as induced by topical application of a nonivamide/nicoboxil cream.

    PubMed

    Warnecke, Jan M; Wendt, Thomas; Winkler, Stefan; Schak, Matthias; Schiffer, Thorsten; Kohl-Bareis, Matthias

    2014-02-01

    Topical agents like nonivamide and nicoboxil induce hyperaemisation and increase cutaneous blood flow and temperature. This study aimed to determine the effects of a nonivamide-nicoboxil cream on haemodynamics in the skin and calf muscle, via optical spectroscopy, discriminating between the changes for skin and muscle. Optical spectroscopy was applied in the visible (VIS) and near-infrared (NIR) wavelength range. The study determined the effect of the cream on changes in oxygenated (ΔoxyHb) and deoxygenated (ΔdeoxyHb) haemoglobin in skin and muscle, as well as on tissue oxygen saturation (SO2) in the skin of 14 healthy subjects. The left and right calves of the subjects were either treated with nonivamide-nicoboxil cream or were sham-administered. NIR spectroscopy allows noninvasive in-vivo examination of the oxygenation of human skeletal muscle. Topical administration of the nonivamide-nicoboxil cream significantly increased the concentration of oxygenated haemoglobin and tissue oxygen saturation in the skin, as well as the concentration of oxygenated haemoglobin in the muscle of the treated legs after 15 min, but with stronger and faster effects in the skin. The topical application of the nonivamide-nicoboxil cream increased blood flow in (smaller vessels of) the skin and muscle tissues.

  8. Antibacterial activity and therapeutic efficacy of Fl-P(R)P(R)P(L)-5, a cationic amphiphilic polyproline helix, in a mouse model of staphylococcal skin infection.

    PubMed

    Thangamani, Shankar; Nepal, Manish; Chmielewski, Jean; Seleem, Mohamed N

    2015-01-01

    The antibacterial activities and therapeutic efficacy of the cationic, unnatural proline-rich peptide Fl-P(R)P(R)P(L)-5 were evaluated against multidrug-resistant Staphylococcus aureus in a mouse model of skin infection. Fl-P(R)P(R)P(L)-5 showed potent activity against all clinical isolates of S. aureus tested, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA, respectively). Fl-P(R)P(R)P(L)-5 was also superior in clearing established in vitro biofilms of S. aureus and Staphylococcus epidermidis, compared with the established antimicrobials mupirocin and vancomycin. Additionally, topical treatment of an MRSA-infected wound with Fl-P(R)P(R)P(L)-5 enhanced wound closure and significantly reduced bacterial load. Finally, 0.5% Fl-P(R)P(R)P(L)-5 significantly reduced the levels of the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) in wounds induced by MRSA skin infection. In conclusion, the results of this study suggest the potential application of Fl-P(R)P(R)P(L)-5 in the treatment of staphylococcal skin infections.

  9. Antibacterial activity and therapeutic efficacy of Fl-PRPRPL-5, a cationic amphiphilic polyproline helix, in a mouse model of staphylococcal skin infection

    PubMed Central

    Thangamani, Shankar; Nepal, Manish; Chmielewski, Jean; Seleem, Mohamed N

    2015-01-01

    The antibacterial activities and therapeutic efficacy of the cationic, unnatural proline-rich peptide Fl-PRPRPL-5 were evaluated against multidrug-resistant Staphylococcus aureus in a mouse model of skin infection. Fl-PRPRPL-5 showed potent activity against all clinical isolates of S. aureus tested, including methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA, respectively). Fl-PRPRPL-5 was also superior in clearing established in vitro biofilms of S. aureus and Staphylococcus epidermidis, compared with the established antimicrobials mupirocin and vancomycin. Additionally, topical treatment of an MRSA-infected wound with Fl-PRPRPL-5 enhanced wound closure and significantly reduced bacterial load. Finally, 0.5% Fl-PRPRPL-5 significantly reduced the levels of the inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) in wounds induced by MRSA skin infection. In conclusion, the results of this study suggest the potential application of Fl-PRPRPL-5 in the treatment of staphylococcal skin infections. PMID:26543355

  10. Tumorigenesis in athymic nude mouse skin by chemical carcinogens and ultraviolet light

    SciTech Connect

    Anderson, L.M.; Rice, J.M.

    1987-01-01

    A variety of established skin tumorigenesis protocols were tested for efficacy on athymic nu/nu mice (BALB/c background) and compared on euthymic nu/+ counterparts. Chemical carcinogens and UV light were applied to the ears of 10 mice of each sex and genotype for each group. Treatments were: 0.5 mg 7,12-dimethylbenz(a)anthracene ((DMBA) CAS: 57-97-6) to each ear; 0.125 mg DMBA to each ear, followed by 0.1 microgram 12-O-tetradecanoylphorbol-13-acetate ((TPA) CAS: 16561-29-8) twice weekly for 56 weeks; 0.2 mg N-nitroso-N-methylurea ((NMU) CAS: 684-93-5; 1% in acetone, 20 microliter) to each ear; 0.1 mg NMU to each ear weekly for 30 weeks; 0.2 mg NMU to each ear, followed by TPA twice weekly for 56 weeks; two ip doses of N-nitroso-N-ethylurea ((NEU) CAS: 759-73-9; 25 mg/kg each), followed by TPA twice weekly topically for 56 weeks; and exposure to sunlamps (250- to 400-nm emission) two or three times per week for 20 weeks, for a total dose of 3.7 X 10(5) J/m2. The chemical treatments caused mainly squamous papillomas and carcinomas, sebaceous adenomas and adenocarcinomas, and basal cell tumors, which appeared both on the skin of the ears and elsewhere. UV light caused squamous tumors, basal cell tumors, and sarcomas. Ear skin of the nu/nu mice developed significantly more squamous tumors than those of nu/+ mice after DMBA-TPA, NMU-TPA, NEU-TPA, repeated NMU, or UV light. Similar results were obtained for the skin of the heads and bodies. Even a single dose of NMU caused a few tumors on the nude, but not the euthymic, mice. A single dose of DMBA caused primarily sebaceous adenomas, distributed at random over the entire bodies. These results show that, contrary to previous reports, nude mice are sensitive to skin tumorigenesis, more so than euthymic nu/+ mice similarly exposed to diverse types of carcinogen and treatment protocols.

  11. Topical retinoids in skin ageing: a focused update with reference to sun-induced epidermal vitamin A deficiency.

    PubMed

    Sorg, Olivier; Saurat, Jean-Hilaire

    2014-01-01

    Vitamin A is an important constituent of the epidermis, where it plays a crucial role in epidermal turnover. A deficiency of epidermal vitamin A may be the consequence of nutritional vitamin A deficiency, exposure to sunlight or any UV source, oxidative stress or chronological ageing. As a consequence, any treatment aiming at increasing epidermal vitamin A would exert a protective effect against these deleterious conditions. Retinoids may counteract some deleterious actions of UV radiation by physical and biological mechanisms. Topical natural retinoic acid precursors such as retinaldehyde or retinol are less irritant than acidic retinoids and may prevent epidermal vitamin A deficiency due to nutritional deficiency, exposure to sunlight or any condition leading to free radical production. Retinoids may be combined with other compounds with complementary actions against ageing, nutritional deficiency and cancer, such as antioxidants, to potentiate their beneficial effects in the skin.

  12. Evaluation of Skin Penetration of Diclofenac from a Novel Topical Non Aqueous Solution: A Comparative Bioavailability Study

    PubMed Central

    Nivsarkar, Manish; Patel, Ketan R.; Patel, Dixit D.

    2015-01-01

    Introduction Different topical formulations of diclofenac have varying skin penetration profile. Recent advances in science and technology has led to the development of many new formulations of drugs for topical drug delivery. One such technological development has led to the innovation of Dynapar QPS, a novel, non-aqueous, quick penetrating solution (QPS) of diclofenac diethylamine. Aim This study was aimed to measure the total exposure from the drug penetrating the skin in healthy human subjects and comparing the relative systemic bioavailability of Dynapar QPS® with diclofenac emulgel. Materials and Methods A 200 mg of diclofenac from either Dynapar QPS® (5 ml) or emulgel (20 g) was applied on back of subject as per the randomisation schedule. Blood samples were collected up to 16 hours post drug application. Plasma concentration of diclofenac was measured by pre-validated HPLC method. Pharmacokinetic (PK) parameters like Cmax, Tmax, t1/2, AUC0-t, AUC0-∞, and Kel, of diclofenac were determined for both the formulations. Results Mean Cmax after administration of Dynapar QPS® and diclofenac emulgel were 175.93 and 40.04 ng/ml, respectively. Tmax of diclofenac was almost half with QPS compared to emulgel (5.24 hrs versus 9.53 hrs respectively). The mean AUC0–t and AUC0-∞ after administration of Dynapar QPS® was higher as compared to diclofenac emulgel (AUC0–t: 1224.19 versus 289.78 ng.h/ml, respectively; AUC0-∞: 1718.21 versus 513.83 ng.h/ml, respectively). None of the subject experienced any adverse event during the study. Conclusion The results indicate an enhanced penetration and subsequent absorption of diclofenac from Dynapar QPS® as compared to diclofenac emulgel. Higher penetration is likely to translate into better pain relief in patients. PMID:26816910

  13. In Vivo Assessment of Acute UVB Responses in Normal and Xeroderma Pigmentosum (XP-C) Skin-Humanized Mouse Models

    PubMed Central

    García, Marta; Llames, Sara; García, Eva; Meana, Alvaro; Cuadrado, Natividad; Recasens, Mar; Puig, Susana; Nagore, Eduardo; Illera, Nuria; Jorcano, José Luis; Del Rio, Marcela; Larcher, Fernando

    2010-01-01

    In vivo studies of UVB effects on human skin are precluded by ethical and technical arguments on volunteers and inconceivable in cancer-prone patients such as those affected with Xeroderma Pigmentosum (XP). Establishing reliable models to address mechanistic and therapeutic matters thus remains a challenge. Here we have used the skin-humanized mouse system that circumvents most current model constraints. We assessed the UVB radiation effects including the sequential changes after acute exposure with respect to timing, dosage, and the relationship between dose and degree-sort of epidermal alteration. On Caucasian-derived regenerated skins, UVB irradiation (800 J/m2) induced DNA damage (cyclobutane pyrimidine dimers) and p53 expression in exposed keratinocytes. Epidermal disorganization was observed at higher doses. In contrast, in African descent–derived regenerated skins, physiological hyperpigmentation prevented tissue alterations and DNA photolesions. The acute UVB effects seen in Caucasian-derived engrafted skins were also blocked by a physical sunscreen, demonstrating the suitability of the system for photoprotection studies. We also report the establishment of a photosensitive model through the transplantation of XP-C patient cells as part of a bioengineered skin. The inability of XP-C engrafted skin to remove DNA damaged cells was confirmed in vivo. Both the normal and XP-C versions of the skin-humanized mice proved proficient models to assess UVB-mediated DNA repair responses and provide a strong platform to test novel therapeutic strategies. PMID:20558577

  14. Inhibition of phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate-caused inflammatory responses in SENCAR mouse skin by black tea polyphenols.

    PubMed

    Katiyar, S K; Mukhtar, H

    1997-10-01

    Over the past 10 years many studies from several laboratories defined anticarcinogenic and anti-inflammatory effects of tea, a widely consumed beverage by the human population. Much of such work has been conducted with green tea or its polyphenolic constituents. Regarding black tea, studies have shown that its water extract affords protection against tumor promotion caused by chemical carcinogens or ultraviolet B radiation in murine skin carcinogenesis models. Several studies have shown that topical application of chemical tumor promoters to murine skin results in the induction of epidermal edema, hyperplasia and ornithine decarboxylase (ODC) and cyclo-oxygenase activities, and interleukin-1 alpha (IL-1alpha) and ODC mRNA expression. In this study, we assessed whether topical application of polyphenols isolated from black tea leaves (hereafter referred to as BTP) mainly consisting of theaflavine gallates and (-)-epigallocatechin-3-gallate, inhibits phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-caused induction of these markers of inflammatory responses in murine skin. Topical application of BTP (6 mg in 0.2 ml acetone/animal) 30 min prior to TPA application on to the mouse skin resulted in significant inhibition against TPA-caused induction of epidermal edema (40%, P < 0.01), hyperplasia (57%, P < 0.005), leukocytes infiltration (50%), and induction of epidermal ODC (57%) and pro-inflammatory cytokine IL-1alpha mRNA expression (69%). Pre-application of BTP to that of TPA also resulted in significant inhibition of TPA-caused induction of epidermal ODC (23-73%, P < 0.005-0.0001), and cyclo-oxygenase, in terms of prostaglandins metabolites formation (38-65%, P < 0.01-0.0005), enzyme activities. Our data indicate that the inhibition of TPA-caused changes in these markers of inflammatory responses in murine skin by BTP may be one of the possible mechanisms of chemopreventive effects associated with black tea against tumorigenesis. The results

  15. Mouse skin tumor-initiating activity of 5-, 7-, and 12-methyl- and fluorine-substituted benz(a)anthracenes

    SciTech Connect

    Wood, A.W.; Levin, W.; Chang, R.L.; Conney, A.H.; Slaga, T.J.; O'Malley, R.F.; Newman, M.S.; Buhler, D.R.; Jerina, D.M.

    1982-09-01

    Eleven methyl- and/or fluorine-substitued benz(a)anthracenes were evaluated for tumor-initating activity on mouse skin. Outbred CD-1 and outbred Sencar mice received a single topical application of the hydrocarbons followed by twice weekly application of the tumor promoter 12-O-tetradecanoylphorbol 13-acetate for 16-26 weeks. 7, 12-DMBA was almost two orders of magnitude more active as a tumor-initator than 7- and 12-methylbenz(a)anthracene. Methyl substitution at the 7- and 7,12-positions of benz(a)anthracence was significantly more effective in the enhancement of tumorigenic activity than fluorine substitution at these positions. Although 7-fluorobenz(a)anthracene, 12-fluorobenz(a)anthracene, and 7,12-difluorobenz(a)anthracene had only 0.15, 0.26, and less than 0.005 times the tumor-initiating activity of their respective methyl-substituted derivatives, they were severalfold more active than benz(a)anthracene. 7-Fluorobenz(a)anthracene was slightly less active than 12-fluorobenz(a)anthracene, whereas 7-methylbenz(a)anthracene was about twofold more active than 12-methylbenz(a)anthracene. For 7,12-disubstituted benz(a)anthracenes, 7-methyl-12-fluorobenz(a)anthracene was more than twice as tumorigenic as 7-fluoro-12-methylbenz(a)anthracene, but each was individually more active than 7-methylbenz(a)anthracene and 12-methylbenz(a)anthracene, respectively. Both fluorinated compounds were much less active than 7,12-DMBA. Substitution of fluorine or methyl at the 5-position of 7-methylbenz(a)anthracene and substition of fluorine at the 5-position of 12-methylbenz(a)anthracene dramatically reduced their tumorigenic activity.

  16. Topical Nicotinamide Improves Tissue Regeneration in Excisional Full-Thickness Skin Wounds: A Stereological and Pathological Study

    PubMed Central

    Ashkani Esfahani, Soheil; Khoshneviszadeh, Mahsima; Namazi, Mohammad Reza; Noorafshan, Ali; Geramizadeh, Bita; Nadimi, Elham; Razavipour, Seyedeh Tahereh

    2015-01-01

    Background: Nicotinamide (NA), the active form of vitamin-B3, is hypothesized to have positive effects on the process of wound healing; it has anti-inflammatory, antioxidant, and immunomodulatory properties, as well as an epithelization inducing action. Objectives: In the present study, we aimed to determine the effects of topical administration of NA on skin wounds, based on histomorphometrical and pathological criteria. Materials and Methods: In this study, 36 male Sprague-Dawley rats (220 ± 20 g each), with 1 cm2 circular full-thickness wounds on their backs were divided into three groups (n = 12): NA group, was treated daily with a Nicotinamide 2% gel , untreated group (control), and base group, which were treated with the vehicle (base) of the gel (carboxymethylcellulose). Skin biopsies were prepared for microscopic analyses. Inflammation, granulation tissue formation, ulceration, epithelization, wound closure rate, fibroblast proliferation, collagen synthesis, and vascularization were studied criteria. Results: The results revealed that besides improving the wound healing by its anti-inflammatory, antioxidant, and epithelization inducing effects, NA also improved tissue regeneration through the increment of fibroblast proliferation, collagen synthesis, and vascularization. Conclusions: In spite of the few reported side effects, NA can be introduced as an effective agent on the wound healing process, an adjuvant therapy and possibly a treatment by itself. However, its chemical characteristics, as well as possible adverse effects warrants further research. PMID:26839851

  17. Polymeric nanosponges as an alternative carrier for improved retention of econazole nitrate onto the skin through topical hydrogel formulation.

    PubMed

    Sharma, Renuka; Pathak, Kamla

    2011-08-01

    The present study was carried out to exploit the feasibility of using polymeric nanosponges as an alternative carrier for targeting econazole nitrate (EN) to the skin through topical hydrogel formulation. Nanosponges prepared by emulsion solvent diffusion method were evaluated for various physicochemical parameters and in vitro drug release. The nanosponges of EN were discrete free flowing nanosized particles with perforated orange peel like morphology as visualized by SEM. The nanosponge formulated using PVA:EC (3:2) displayed highest in vitro release after 12?h in phosphate buffer (pH 6.8) that fitted matrix model. Selected nanosponge was formulated as Carbopol 934 NF hydrogel using varying concentrations of permeation enhancers propylene glycol and N-methyl-2-pyrrolidone. The EN nanosponge-loaded hydrogels (F0?F7) were evaluated for pharmacotechnical properties and irritation studies on rat skin. On the basis of various evaluation parameters F7 with an equilibrium swelling of 0.944?g/g after 4?h, low firmness and high adhesiveness, a flux rate of 1540.2 (?g/cm(2).h) and that exhibited a controlled release of EN for 12?h was selected as best hydrogel. The DRS and DSC spectra of F7 confirmed stability of drug in the delivery system and absence of drug polymer interaction in nanosponges.

  18. Therapeutic Efficacy of Topically Applied Antioxidant Medicinal Plant Extracts in a Mouse Model of Experimental Dry Eye

    PubMed Central

    Lee, Jee Bum; Li, Ying; Choi, Ji Suk; Lee, Hyo Seok

    2016-01-01

    Purpose. To investigate the therapeutic effects of topical administration of antioxidant medicinal plant extracts in a mouse model of experimental dry eye (EDE). Methods. Eye drops containing balanced salt solution (BSS) or 0.001%, 0.01%, and 0.1% extracts were applied for the treatment of EDE. Tear volume, tear film break-up time (BUT), and corneal fluorescein staining scores were measured 10 days after desiccating stress. In addition, we evaluated the levels of interleukin- (IL-) 1β, tumor necrosis factor- (TNF-) α, IL-6, interferon- (IFN-) γ, and IFN-γ associated chemokines, percentage of CD4+C-X-C chemokine receptor type 3 positive (CXCR3+) T cells, goblet cell density, number of 4-hydroxy-2-nonenal (4-HNE) positive cells, and extracellular reactive oxygen species (ROS) production. Results. Compared to the EDE and BSS control groups, the mice treated with topical application of the 0.1% extract showed significant improvements in all clinical parameters, IL-1β, IL-6, TNF-α, and IFN-γ levels, percentage of CD4+CXCR3+ T cells, goblet cell density, number of 4-HNE-positive cells, and extracellular ROS production (P < 0.05). Conclusions. Topical application of 0.1% medicinal plant extracts improved clinical signs, decreased inflammation, and ameliorated oxidative stress marker and ROS production on the ocular surface of the EDE model mice. PMID:27313829

  19. Citrinin-generated reactive oxygen species cause cell cycle arrest leading to apoptosis via the intrinsic mitochondrial pathway in mouse skin.

    PubMed

    Kumar, Rahul; Dwivedi, Premendra D; Dhawan, Alok; Das, Mukul; Ansari, Kausar M

    2011-08-01

    The mycotoxin, citrinin (CTN), is a contaminant of various food and feed materials. Several in vivo and in vitro studies have demonstrated that CTN has broad toxicity spectra; however, dermal toxicity is not known. In the present investigation, dermal exposure to CTN was undertaken to study oxidative stress, DNA damage, cell cycle arrest, and apoptosis in mouse skin. A single topical application of CTN caused significant change in oxidative stress markers, such as lipid peroxidation, protein carbonyl content, glutathione (GSH) content, and antioxidant enzymes in a dose-dependent (25-100 μg/mouse) and time-dependent (12-72 h) manner. Single topical application of CTN (50 μg/mouse) for 12-72 h caused significant enhancement in (1) reactive oxygen species (ROS); (2) cell cycle arrest at the G0/G1 phase (30-71%) and G2/M phase (56-65%) along with the induction of apoptosis (3.6-27%); (3) expression of p53, p21/waf1; (4) Bax/Bcl₂ ratio and cytochome c release; and (5) activities of caspase 9 (22-46%) and 3 (42-54%) as well as increased poly(ADP-ribose) polymerase cleavage. It was also observed that pretreatment with bio-antioxidants viz butylated hydroxyanisole (55 μmol/100 μl), quercetin (10 μmol/100 μl), or α-tocopherol (40 μmol/100 μl) resulted in decreases of ROS generation, arrest in the G0/G1 phase of the cell cycle, and apoptosis. These data confirm the involvement of ROS in apoptosis and suggest that these bio-antioxidants may be useful in the prevention of CTN-induced dermal toxicity.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

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

    2016-01-01

    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.

  2. Enhanced regenerative healing efficacy of a highly skin-permeable growth factor nanocomplex in a full-thickness excisional mouse wound model

    PubMed Central

    Bae, Il-Hong; Park, Jin Woo; Kim, Dae-Yong

    2014-01-01

    Exogenous administration of growth factors has potential benefits in wound healing; however, limited percutaneous absorption, inconsistent efficacy, and the need for high doses have hampered successful clinical use. To overcome these restrictions, we focused on the development of a topical formulation composed of highly skin-permeable multimeric nanocomplex of growth factors. In the present study, we fused low-molecular-weight protamine (LMWP) with epidermal growth factor (EGF), insulin-like growth factor 1 (IGF-I), and platelet-derived growth factor A ligand (PDGF-A) (producing recombinant [r]LMWP-EGF, rLMWP-IGF-I, and rLMWP-PDGF-A, respectively) via genetic modification. Then, we used in vitro cell proliferation studies to assess the biological activity and the benefits of the combination. The LMWP-conjugated growth factors were complexed with low-molecular-weight heparin (LMWH) and formulated with Poloxamer 188 as a delivery vehicle. After confirming the enhanced skin permeability, in vivo studies were performed to assess whether the LMWP-conjugated growth factor nanocomplex formulations accelerated the healing of full-thickness wounds in mice. The LMWP-conjugated growth factors were biologically equivalent to their native forms, and their combination induced greater fibroblast proliferation. rLMWP-EGF showed significantly enhanced permeability and cumulative permeation, and the rates for rLMWP-IGF-I and rLMWP-PDGF-A, across excised mouse skin, were 124% and 164% higher, respectively, than for the native forms. The LMWP-fused growth factors resulted in formation of nanocomplexes (23.51±1.12 nm in diameter) in combination with LMWH. Topical delivery of growth factors fused with LMWP accelerated wound re-epithelialization significantly, accompanied by the formation of healthy granulation tissue within 9 days compared with a free–growth factor complex or vehicle. Thus, the LMWP-conjugated growth factor nanocomplex can induce rapid, comprehensive healing and may

  3. The effect of vehicle on the diffusion of salicylic acid through hairless mouse skin.

    PubMed

    Sloan, K B; Siver, K G; Koch, S A

    1986-08-01

    The solubilities of salicylic acid in, and the fluxes through, hairless mouse skin from isopropyl myristate, 1-octanol, 1-propanol, propylene glycol, and formamide have been determined experimentally. Values for permeability coefficients (Kp) corresponding to the respective fluxes were determined from: flux/solubility = Kp. These values were then compared with values for the respective partition coefficients (P) which were calculated from the known solubility parameters for the vehicles (delta v), salicylic acid (delta i), and skin (delta s). Two different delta i values were used to calculate theoretical P values, one based on the peak solubility method and the other based on calculation from group contributions (11 and 14.4 (cal/cm3)1/2, respectively). There was good correlation between the values for theoretical log P - 1.42 and experimental log Kp for the delivery of salicylic acid from vehicles exhibiting solubility parameters in the range of delta v = 10-18 (cal/cm3)1/2, when delta i was assumed to be 14.4 (cal/cm3)1/2. There was also a good correlation between the values for theoretical log P - 2.09 and experimental log Kp for vehicles exhibiting solubility parameters in the range of delta v = 7.6-10 (cal/cm3)1/2, when delta i was assumed to be 11 (cal/cm3)1/2. Two different delta i values were used because salicylic acid apparently behaves like a polar molecule in polar vehicles and a nonpolar molecule in nonpolar vehicles. Qualitatively, fluxes and permeability coefficients were found to be inversely dependent on drug solubility in the vehicles, with a minimum that corresponded approximately to the point where delta v = delta i, and the minimum within the theoretical P curve.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    PubMed Central

    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

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

    PubMed

    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

  6. Mapping tissue shear modulus on Thiel soft-embalmed mouse skin with shear wave optical coherence elastography

    NASA Astrophysics Data System (ADS)

    Song, Shaozhen; Joy, Joyce; Wang, Ruikang K.; Huang, Zhihong

    2015-03-01

    A quantitative measurement of the mechanical properties of biological tissue is a useful assessment of its physiologic conditions, which may aid medical diagnosis and treatment of, e.g., scleroderma and skin cancer. Traditional elastography techniques such as magnetic resonance elastography and ultrasound elastography have limited scope of application on skin due to insufficient spatial resolution. Recently, dynamic / transient elastography are attracting more applications with the advantage of non-destructive measurements, and revealing the absolute moduli values of tissue mechanical properties. Shear wave optical coherence elastography (SW-OCE) is a novel transient elastography method, which lays emphasis on the propagation of dynamic mechanical waves. In this study, high speed shear wave imaging technique was applied to a range of soft-embalmed mouse skin, where 3 kHz shear waves were launched with a piezoelectric actuator as an external excitation. The shear wave velocity was estimated from the shear wave images, and used to recover a shear modulus map in the same OCT imaging range. Results revealed significant difference in shear modulus and structure in compliance with gender, and images on fresh mouse skin are also compared. Thiel embalming technique is also proven to present the ability to furthest preserve the mechanical property of biological tissue. The experiment results suggest that SW-OCE is an effective technique for quantitative estimation of skin tissue biomechanical status.

  7. Transcriptional changes in organoculture of full-thickness human skin following topical application of all-trans retinoic acid

    PubMed Central

    Gillbro, J M; Al-Bader, T; Westman, M; Olsson, M J; Mavon, A

    2014-01-01

    Synopsis Objective Retinoids are used as therapeutic agents for numerous skin diseases, for example, psoriasis, acne and keratinization disorders. The same substances have also been recognized in the treatment for hyperpigmentation disorders such as melasma. Other studies on photo-damaged skin have shown that retinoids reduce wrinkles, surface roughness, mottled pigmentation, and visual skin appearance as a whole. We tested the hypothesis that an organoculture of full-thickness human skin could be used as a preclinical model to investigate the retinoid transcriptional profile in human skin in vitro. Methods Full-thickness skin explants were exposed to topically applied all-trans retinoic acid (RA) for 24 h. The gene expression profile was analysed using oligonucleotide microarrays, and data were validated with real-time (RT) PCR. Results We showed that the expression of 93 genes was significantly altered more than twofold. Several of the altered genes, for example, KRT4, CYP26 and LCN2, have previously been shown to be affected by RA in keratinocyte monocultures, reconstructed epidermis and skin biopsies from patients treated topically or orally with RA. In addition, genes, such as SCEL, NRIP1, DGAT2, RDH12 EfnB2, MAPK14, SAMD9 and CEACAM6 not previously reported to be affected by RA in human skin, were identified for the first time in this study. Conclusion The results in the present study show that full-thickness human explants represent a valuable pre-clinical model for studying the effects of retinoids in skin. Résumé Objectif Les rétinoïdes sont utilisés comme agents thérapeutiques pour de nombreuses maladies de la peau, p.ex. le psoriasis, l'acné et les troubles de la kératinisation. Les mêmes substances ont également été reconnues dans le traitement des troubles de l' hyperpigmentation tels que le melasma. D'autres études sur la peau photo-endommagée ont montré que les rétinoïdes réduisent les rides, la rugosité de la surface, la

  8. Activation of primary sensory neurons by the topical application of capsaicin on the epidermis of a re-innervated organotypic human skin model.

    PubMed

    Lebonvallet, Nicolas; Pennec, Jean-Pierre; Le Gall-Ianotto, Christelle; Chéret, Jérémy; Jeanmaire, Christine; Carré, Jean-Luc; Pauly, Gilles; Misery, Laurent

    2014-01-01

    Using an ex vivo skin-nerve preparation, skin and nerve cells were reconstituted into a single unit and maintained in a nutrient medium bath until required experimentally. Our objective was to use the epidermis as a relay for the induction of an electric current to the neurons following the topical application of capsaicin on the skin epidermis of the skin explant, an agonist of the TRPV1 channel implicated in pruritus and pain. After 10-20 days of coculture to form the re-innervated skin model, we applied a solution of capsaicin directly on the epidermis of the skin explant (4 μm). The resulting current was recorded using a path-clamp technique on the neuronal fibres. Following the topical application of capsaicin, spontaneous activity was triggered, as characterised by repetitive spikes with periods of 125, 225 or 275 ms. This study demonstrates that the skin explant and nerve cells preparation may receive stimuli and be used to screen molecules or to study signal transmission.

  9. The plasma membrane-associated NADH oxidase (ECTO-NOX) of mouse skin responds to blue light

    NASA Technical Reports Server (NTRS)

    Morre, D. James; Morre, Dorothy M.

    2003-01-01

    NADH oxidases of the external plasma membrane surface (ECTO-NOX proteins) are characterized by oscillations in activity with a regular period length of 24 min. Explants of mouse skin exhibit the oscillatory activity as estimated from the decrease in A(340) suggesting that individual ECTO-NOX molecules must somehow be induced to function synchronously. Transfer of explants of mouse skin from darkness to blue light (495 nm, 2 min, 50 micromol m(-1) s(-1)) resulted in initiation of a new activity maximum (entrainment) with a midpoint 36 min after light exposure followed by maxima every 24 min thereafter. Addition of melatonin resulted in a new maximum 24 min after melatonin addition. The findings suggest that the ECTO-NOX proteins play a central role in the entrainment of the biological clock both by light and by melatonin.

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

    PubMed

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

    2011-04-01

    The fluxes of charged and nonionic molecules across hairless mouse skin (HMS) were induced by direct current iontophoresis and used to characterize the transport pathways of the epidermal membrane. Experimental data were used to determine permeability coefficients from which the effective pore radii (Rp) of the transport pathways were calculated. Permeants used in these experiments were nonionic permeants (urea, mannitol, and raffinose), monovalent cationic permeants (sodium, tetraethylammonium, and tetraphenylphosphonium ions), and monovalent anionic permeants (chloride, salicylate, and taurocholate ions). The Rp estimates obtained by the anionic permeant pairs were 49, 22, and 20 Å for the chloride/salicylate (Cl:SA), chloride/taurocholate (Cl:TC), and salicylate/taurocholate (SA:TC) pairs, respectively; with the cationic permeant pairs, the Rp values obtained were 19, 30, and 24 Å for the sodium/tetraethylammonium (Na:TEA), sodium/tetraphenylphosphonium (Na:TPP), and the tetraethylammonium/tetraphenylphosphonium (TEA:TPP) pairs, respectively. Rp estimates for HMS obtained from nonionic permeant experiments ranged from 6.7 to 13.4 Å. When plotted versus their respective diffusion coefficients, all of the permeability coefficients for the cationic permeants were greater than those of the anionic permeants. Additionally, the magnitudes of permeability coefficients determined in the current study with HMS were of the same order of magnitude as those previously determined in our laboratory using human epidermal membrane under similar iontophoresis conditions. PMID:21259234

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

    PubMed

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

    2011-04-01

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

  12. Protective effect of alpha-tocopherol-6-O-phosphate against ultraviolet B-induced damage in cultured mouse skin.

    PubMed

    Nakayama, Satomi; Katoh, Eiko M; Tsuzuki, Toshi; Kobayashi, Shizuko

    2003-08-01

    The ability of the novel water-soluble provitamin E, alpha-tocopherol-6-O-phosphate, to protect against ultraviolet B-induced damage in cultured mouse skin was investigated and compared with the protectiveness of alpha-tocopherol acetate in cultured mouse skin. Pretreatment of skin with 0.5% (9.4 mM) alpha-tocopherol-6-O-phosphate in medium for 3 h significantly prevented such photodamage as sunburn cell formation, DNA degradation, and lipid peroxidation, which were induced in control cultured skin by a single dose of ultraviolet B irradiation at 0 to 40 kJ per m2 (290-380 nm, maximum 312 nm). This protection was greater than that seen with alpha-tocopherol acetate, the most common provitamin E that is used in commercial human skin care products. The concentration of alpha-tocopherol in cultured skin pretreated with 0.5% alpha-tocopherol-6-O-phosphate rose to approximately two to three times that found in the control skin and the reduction in cutaneous alpha-tocopherol that was induced by ultraviolet irradiation was significantly inhibited. In the group pretreated with 0.5% alpha-tocopherol acetate, however, conversion of alpha-tocopherol acetate to alpha-tocopherol was not observed, although the level of provitamin incorporated into the cultured skin was the same as that for alpha-tocopherol-6-O-phosphate. These findings indicated that the enhanced ability of alpha-tocopherol-6-O-phosphate to protect against ultraviolet B-induced skin damage compared with alpha-tocopherol acetate may have been due to alpha-tocopherol-6-O-phosphate's conversion to alpha-tocopherol. Moreover, following pretreatment with a 0.5% alpha-tocopherol-6-O-phosphate, alpha-tocopherol-6-O-phosphate was incorporated into the human skin in a three-dimensional model and 5% of the incorporated alpha-tocopherol-6-O-phosphate was converted to alpha-tocopherol. These results suggest that treatment with the novel provitamin E, alpha-tocopherol-6-O-phosphate may be useful in preventing ultraviolet

  13. Clindamycin Topical

    MedlinePlus

    ... topical clindamycin.you should know that abrasive or medicated soaps and skin products that contain alcohol may ... in, tightly closed, and out of reach of children. Store it at room temperature and away from ...

  14. Mometasone Topical

    MedlinePlus

    Mometasone comes as a topical cream, ointment, and lotion. It usually is applied externally once a day. ... affected skin areas once daily.To apply the lotion, place a few drops on the affected areas ...

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

    PubMed Central

    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

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

    PubMed

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

    2007-01-01

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

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

    PubMed

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

    2015-11-01

    Solar ultraviolet irradiation is an environmental carcinogen that causes skin cancer. Caspase-7 is reportedly expressed at reduced levels in many cancers. The present study was designed to examine the role of caspase-7 in solar-simulated light (SSL)-induced skin cancer and to elucidate its underlying molecular mechanisms. Our study revealed that mice with genetic deficiency of caspase-7 are highly susceptible to SSL-induced skin carcinogenesis. Epidermal hyperplasia, tumor volume and the average number of tumors were significantly increased in caspase-7 knockout (KO) mice compared with SKH1 wild-type mice irradiated with SSL. The expression of cell proliferation markers, such as survivin and Ki-67, was elevated in SSL-irradiated skin of caspase-7 KO mice compared with those observed in SSL-exposed wild-type SKH1 mouse skin. Moreover, SSL-induced apoptosis was abolished in skin from caspase-7 KO mice. Two-dimensional gel electrophoresis, followed by matrix-assisted laser desorption/ionization-time-of-flight analysis of skin tissue lysates from SSL-irradiated SKH1 wild-type and caspase-7 KO mice revealed an aberrant induction of keratin-17 in caspase-7 KO mice. Immunohistochemical analysis of skin tumors also showed an increase of keratin-17 expression in caspase-7 KO mice compared with SKH1 wild-type mice. The expression of keratin-17 was also elevated in SSL-irradiated caspase-7 KO keratinocytes as well as in human basal cell carcinomas. The in vitro caspase activity assay showed keratin-17 as a substrate of caspase-7, but not caspase-3. Overall, our study demonstrates that genetic loss of caspase-7 promotes SSL-induced skin carcinogenesis by blocking caspase-7-mediated cleavage of keratin-17. PMID:26271098

  18. [Clinical trial of a topical preparation containing urea, sunflower oil, evening primrose oil, wheat germ oil and sodium pyruvate, in several hyperkeratotic skin conditions].

    PubMed

    Ferrando, J

    1986-01-01

    A topical clinical trial with preparations containing urea and sodium pyruvate has been made. It was used for diverse hyperkeratotic skin conditions (psoriasis, xerosis, pityriasis rubra pilaris, stuccokeratosis, seborrheic dermatitis, stasis dermatitis, pityriasis lichenoides chronica). A month later a clinical improvement was evident in all cases except in pityriasis lichenoides.

  19. Long-term recurrence of nonmelanoma skin cancer after topical methylaminolevulinate photodynamic therapy in a dermato-oncology department*

    PubMed Central

    Cabete, Joana; Rafael, Margarida; Cravo, Mariana; Moura, Cecília; Sachse, Fernanda; Pecegueiro, Manuela

    2015-01-01

    BACKGROUND Most available studies on the efficacy of topical photodynamic therapy focus on short-to medium-term results. Long-term data are scarce. OBJECTIVE To evaluate the long-term efficacy of photodynamic therapy with topical methylaminolevulinate to treat Bowen's disease and basal cell carcinoma in the clinical practice setting of a dermato-oncology department. METHODS The study included patients diagnosed with Bowen's disease or basal cell carcinoma, and who received photodynamic therapy from 2004 to 2008. Treatment protocol and clinical follow-up were standardized. The primary endpoint was clinically observed recurrence in a previous photodynamic therapy-treated area. Descriptive and survival analyses were performed. RESULTS A total of 31 Bowen's disease lesions and 44 superficial basal cell carcinoma were treated, with a median follow-up of 43.5 months. Recurrence was observed in 14 Bowen's disease lesions (53.8%) and in 11 superficial basal cell carcinoma (33.3%). Significantly higher estimates for recurrence rates were found in patients with Bowen's disease (p=0.0036) or those aged under 58 years (p=0.039). The risk of recurrence was higher in patients with Bowen's disease than in those with superficial basal cell carcinoma and younger patients. CONCLUSIONS Recurrence should be considered when choosing to treat non-melanoma skin cancer with photodynamic therapy. Younger age and Bowen's disease were independent predictors for long-term recurrence, suggesting the need to establish an extended period of follow-up for this subset of patients. PMID:26734866

  20. Continuous imaging of the blood vessels in tumor mouse dorsal skin window chamber model by using SD-OCT

    NASA Astrophysics Data System (ADS)

    Peng, Xiao; Yang, Shaozhuang; Yu, Bin; Wang, Qi; Lin, Danying; Gao, Jian; Zhang, Peiqi; Ma, Yiqun; Qu, Junle; Niu, Hanben

    2016-03-01

    Optical Coherence Tomography (OCT) has been widely applied into microstructure imaging of tissues or blood vessels with a series of advantages, including non-destructiveness, real-time imaging, high resolution and high sensitivity. In this study, a Spectral Domain OCT (SD-OCT) system with higher sensitivity and signal-to-noise ratio (SNR) was built up, which was used to observe the blood vessel distribution and blood flow in the dorsal skin window chamber of the nude mouse tumor model. In order to obtain comparable data, the distribution images of blood vessels were collected from the same mouse before and after tumor injection. In conclusion, in vivo blood vessel distribution images of the tumor mouse model have been continuously obtained during around two weeks.

  1. 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.

    PubMed

    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.

  2. Topical Mitomycin-C enhances subbasal nerve regeneration and reduces erosion frequency in the debridement wounded mouse cornea.

    PubMed

    Pal-Ghosh, Sonali; Pajoohesh-Ganji, Ahdeah; Tadvalkar, Gauri; Kyne, Briana M; Guo, Xiaoqing; Zieske, James D; Stepp, Mary Ann

    2016-05-01

    Corneal epithelial basement membrane dystrophies and superficial injuries caused by scratches can lead to recurrent corneal erosion syndrome (RCES). Patients and animals with reduced corneal sensory nerve innervation can also develop recurrent erosions. Multiple wild-type mouse strains will spontaneously develop recurrent corneal erosions after single 1.5 mm debridement wounds. Here we show that this wound is accompanied by an increase in corneal epithelial cell proliferation after wound closure but without a commensurate increase in corneal epithelial thickness. We investigated whether excess corneal epithelial cell proliferation contributes to erosion formation. We found that topical application of Mitomycin C (MMC), a drug used clinically to improve healing after glaucoma and refractive surgery, reduces erosion frequency, enhances subbasal axon density to levels seen in unwounded corneas, and prevents excess epithelial cell proliferation after debridement wounding. These results suggest that topically applied MMC, which successfully reduces corneal haze and scarring after PRK, may also function to enhance subbasal nerve regeneration and epithelial adhesion when used to treat RCES.

  3. Microscopic Delineation of Medulloblastoma Margins in a Transgenic Mouse Model Using a Topically Applied VEGFR-1 Probe1

    PubMed Central

    Wang, Danni; Chen, Ye; Leigh, Steven Y; Haeberle, Henry; Contag, Christopher H; Liu, Jonathan T C

    2012-01-01

    The unambiguous demarcation of tumor margins is critical at the final stages in the surgical treatment of brain tumors because patient outcomes have been shown to correlate with the extent of resection. Real-time high-resolution imaging with the aid of a tumor-targeting fluorescent contrast agent has the potential to enable intraoperative differentiation of tumor versus normal tissues with accuracy approaching the current gold standard of histopathology. In this study, a monoclonal antibody targeting the vascular endothelial growth factor receptor 1 (VEGFR-1) was conjugated to fluorophores and evaluated as a tumor contrast agent in a transgenic mouse model of medulloblastoma. The probe was administered topically, and its efficacy as an imaging agent was evaluated in vitro using flow cytometry, as well as ex vivo on fixed and fresh tissues through immunohistochemistry and dual-axis confocal microscopy, respectively. Results show a preferential binding to tumor versus normal tissue, suggesting that a topically applied VEGFR-1 probe can potentially be used with real-time intraoperative optical sectioning microscopy to guide brain tumor resections. PMID:23323155

  4. Cholera toxin, a potent inducer of epidermal hyperplasia but with no tumor promoting activity in mouse skin carcinogenesis

    SciTech Connect

    Kuroki, T.; Chida, K.; Munakata, K.; Murakami, Y.

    1986-05-29

    Intracutaneous injection of cholera toxin into mice induced epidermal hyperplasia to a greater extent than 12-O-tetra-decanoylphorbol-13-acetate. It also induced adenylate cyclase and through weakly, ornithine decarboxylase of the epidermis. Cholera toxin, however, showed no tumor promoting activity in mouse skin carcinogenesis. In the single stage promotion, cholera toxin (50 ng) was injected once a week for 10 weeks into the skin of SENCAR mice initiated with 25 ..mu..g 7,12-dimethyl-benz(a)anthracene, but no tumors developed. In the two-stage promotion test, cholera toxin (10-100 ng) was injected for one or two weeks into the initiated skin and then mezerein (4 ..mu..g) was applied twice a week for 18 weeks, but the toxin did not increase incidence or numbers of papillomas.

  5. The effects of topical L-selenomethionine on protection against UVB-induced skin cancer when given before, during, and after UVB exposure.

    PubMed

    Burke, Karen E; Zhou, Xueyan; Wang, Yongyin; Commisso, Joel; Keen, Carl L; Nakamura, Robert M; Combs, Gerald F; Wei, Huachen

    2014-10-01

    Previous studies in mice have shown that topical L-selenomethionine (SeMet) can prevent UVB-induced skin cancer when applied continuously before, during, and after the radiation exposure. With topical application of SeMet, selenium levels were shown to increase in the skin and liver, as well as in tumor tissue. Thus, possibly, the timing of SeMet application could affect the degree of inhibition of UVB-tumorigenesis (or maybe even enhance tumorigenesis at some stage). The goal of this research was to determine whether topical SeMet best inhibits UV-induced skin cancer if (a) begun before and continued during and after UVB exposure, (b) if begun before UVB-exposure and discontinued when tumors are first clinically detected, or (c) if begun only after tumors are first detected and continued thereafter. Groups of ten Skh: 1 hairless, non-pigmented mice were treated topically with vehicle lotion, or with SeMet (0.05%) in that vehicle lotion applied either (a) before, during, and after UV exposure, (b) before UV radiation and continued only until the first tumor was detected, or (c) only after the first tumor was detected. In all cases, UV irradiation was discontinued at the time of detection of the first tumor. Optimal inhibition of skin cancer was achieved by application of topical SeMet before, during, and after exposure; significant protection was also attained with application only after the onset of tumors. Notably, statistically significant protection was not seen with SeMet application only prior to tumor detection. These results suggest that even beginning SeMet supplementation late in the process of tumorigenesis can help protect from UV-induced photodamage and skin cancer.

  6. Topical application of retinyl palmitate-loaded nanotechnology-based drug delivery systems for the treatment of skin aging.

    PubMed

    Oliveira, Marcela B; do Prado, Alice Haddad; Bernegossi, Jéssica; Sato, Claudia S; Lourenço Brunetti, Iguatemy; Scarpa, Maria Virgínia; Leonardi, Gislaine Ricci; Friberg, Stig E; Chorilli, Marlus

    2014-01-01

    The objective of this study was to perform a structural characterization and evaluate the in vitro safety profile and in vitro antioxidant activity of liquid crystalline systems (LCS) with and without retinyl palmitate (RP). LCS containing polyether functional siloxane (PFS) as a surfactant, silicon glycol copolymer (SGC) as oil phase, and water in the ratios 30 : 25 : 45 and 40 : 50 : 10 with (OLS(v) = RP-loaded opaque liquid system and TLS(v) = RP-loaded transparent liquid system, respectively) and without (OLS and TLS, respectively) RP were studied. Samples were characterized using polarized light microscopy (PLM) and rheology analysis. In vitro safety profile was evaluated using red cell hemolysis and in vitro cytotoxicity assays. In vitro antioxidant activity was performed by the DPPH method. PLM analysis showed the presence of lamellar LCS just to TLS. Regardless of the presence of RP, the rheological studies showed the pseudoplastic behavior of the formulations. The results showed that the incorporation of RP in LCS improved the safety profile of the drug. In vitro antioxidant activity suggests that LCS presented a higher capacity to maintain the antioxidant activity of RP. PFS-based systems may be a promising platform for RP topical application for the treatment of skin aging. PMID:24772430

  7. Topical Application of Retinyl Palmitate-Loaded Nanotechnology-Based Drug Delivery Systems for the Treatment of Skin Aging

    PubMed Central

    Oliveira, Marcela B.; do Prado, Alice Haddad; Bernegossi, Jéssica; Sato, Claudia S.; Lourenço Brunetti, Iguatemy; Scarpa, Maria Virgínia; Leonardi, Gislaine Ricci; Friberg, Stig E.

    2014-01-01

    The objective of this study was to perform a structural characterization and evaluate the in vitro safety profile and in vitro antioxidant activity of liquid crystalline systems (LCS) with and without retinyl palmitate (RP). LCS containing polyether functional siloxane (PFS) as a surfactant, silicon glycol copolymer (SGC) as oil phase, and water in the ratios 30 : 25 : 45 and 40 : 50 : 10 with (OLSv = RP-loaded opaque liquid system and TLSv = RP-loaded transparent liquid system, respectively) and without (OLS and TLS, respectively) RP were studied. Samples were characterized using polarized light microscopy (PLM) and rheology analysis. In vitro safety profile was evaluated using red cell hemolysis and in vitro cytotoxicity assays. In vitro antioxidant activity was performed by the DPPH method. PLM analysis showed the presence of lamellar LCS just to TLS. Regardless of the presence of RP, the rheological studies showed the pseudoplastic behavior of the formulations. The results showed that the incorporation of RP in LCS improved the safety profile of the drug. In vitro antioxidant activity suggests that LCS presented a higher capacity to maintain the antioxidant activity of RP. PFS-based systems may be a promising platform for RP topical application for the treatment of skin aging. PMID:24772430

  8. Formulation considerations in the design of topical, polymeric film-forming systems for sustained drug delivery to the skin.

    PubMed

    Frederiksen, Kit; Guy, Richard H; Petersson, Karsten

    2015-04-01

    Polymeric film-forming systems (FFSs) are potential drug delivery systems for topical application to the skin. The FFSs form thin and transparent polymeric films in situ upon solvent evaporation. Their application convenience and cosmetic attributes, superior to conventional semi-solids, may offer improved patient compliance. This study represents the first phase of an investigation into the use of FFSs for prolonged dermal drug delivery. FFS formulations were distinguished based on their ability to sustain the release of betamethasone 17-valerate (BMV) in vitro over 72 h. The effect of film-forming polymer (hydrophilic: hydroxypropyl cellulose (Klucel™ LF); hydrophobic: polymethacrylate copolymers (Eudragit® NE and Eudragit® RS), and polyacrylate copolymer (Dermacryl® 79) was first determined, and then the impact of incorporation of plasticisers (triethyl citrate, tributyl citrate, and dibutyl sebacate) was examined. The Klucel film released a significantly higher amount of BMV than the hydrophobic FFS, 42 versus 4 μg/cm(2), respectively. The release was increased when a plasticiser was incorporated, and with higher enhancement ratios achieved with the more lipophilic plasticisers. In conclusion, the results show that FFSs can sustain drug release (hence representing useful systems for prolonged dermal therapy) and emphasise the importance of the formulation on drug delivery, with the type of polymer being of greatest significance.

  9. Salicylic Acid Topical

    MedlinePlus

    ... skin blemishes in people who have acne. Topical salicylic acid is also used to treat skin conditions that involve scaling or overgrowth of skin ... water for 15 minutes.Do not apply topical salicylic acid to skin that is broken, red, swollen, irritated, or infected. ...

  10. A study to assess the occlusivity and moisturization potential of three topical corticosteroid products using the skin trauma after razor shaving (STARS) bioassay.

    PubMed

    Kircik, Leon H

    2014-05-01

    Dysfunction of the epidermal barrier is generally considered a precursor of cutaneous inflammation that can directly contribute to the pathogenesis of skin diseases, notably atopic dermatitis (AD). We also know that topical corticosteroids may actually impair the epidermal barrier by interfering with epidermal lipid synthesis. Therefore, it is important to utilize topical corticosteroids in vehicles that will help at least to enhance the already disrupted epidermal barrier in atopic dermatitis patients. Two studies of identical design were conducted to determine and compare the occlusivity and moisturizing potential of three topical corticosteroid products when applied to skin whose barrier integrity has been disrupted by dry shaving. Findings in both studies showed the clocortolone pivalate cream decreased TEWL better than non-treatment or treatment with hydrocortisone butyrate lotion. Skin surface hydration increased significantly (P<0.001) in all three treated sites, compared to the non-treated damaged control and non-treated normal skin. Clocortolone pivalate cream increased skin surface hydration significantly (P<0.001) better than hydrocortisone butyrate lipocream or hydrocortisone butyrate lotion. These studies showed that clocortolone pivalate cream enhances barrier function by providing occlusion. While understanding of the structure and function of the stratum corneum (SC) and epidermal barrier function has evolved tremendously over the last several decades, and especially over the last 15 years,1 confusion and misinformation still persist. Dysfunction of the epidermal barrier is generally considered a precursor of cutaneous inflammation that can directly contribute to the pathogenesis of skin diseases, notably atopic dermatitis (AD).2,3 Topical steroids are standard of care in treatment of atopic dermatitis. However, we also know that topical corticosteroids may actually impair epidermal barrier by interfering with epidermal lipid synthesis.4,5 In

  11. CDK2 activation in mouse epidermis induces keratinocyte proliferation but does not affect skin tumor development.

    PubMed

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

    2008-08-01

    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 p21(Cip1) and p27(Kip1). 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 K5Cdk4(D158N) mice. The D158N mutation blocks CDK4 kinase activity without interfering with its binding capability. CDK2 activation via overexpression of CDK4(D158N), but not of CDK2, resulted in epidermal hyperplasia. We observed elevated levels of p21(Cip1) in K5Cdk2, but not in K5Cdk4(D158N), epidermis, suggesting that CDK2 overexpression elicits a p21(Cip1) 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.

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

    PubMed Central

    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

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

    PubMed

    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

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

    PubMed

    Logotheti, Stella; Papaevangeliou, Dimitra; Michalopoulos, Ioannis; Sideridou, Maria; Tsimaratou, Katerina; Christodoulou, Ioannis; Pyrillou, Katerina; Gorgoulis, Vassilis; Vlahopoulos, Spiros; Zoumpourlis, Vassilis

    2012-01-01

    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. PMID:22870269

  15. Topical delivery of 5-aminolevulinic acid-encapsulated ethosomes in a hyperproliferative skin animal model using the CLSM technique to evaluate the penetration behavior.

    PubMed

    Fang, Yi-Ping; Huang, Yaw-Bin; Wu, Pao-Chu; Tsai, Yi-Hung

    2009-11-01

    Psoriasis, an inflammatory skin disease, exhibits recurring itching, soreness, and cracked and bleeding skin. Currently, the topical delivery of 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) is an optional treatment for psoriasis which provides long-term therapeutic effects, is non-toxic and enjoys better compliance with patients. However, the precursor of ALA is hydrophilic, and thus its ability to penetrate the skin is limited. Also, little research has provided a platform to investigate the penetration behavior in disordered skin. We employed a highly potent ethosomal carrier (phosphatidylethanolamine; PE) to investigate the penetration behavior of ALA and the recovery of skin in a hyperproliferative murine model. We found that the application of ethosomes produced a significant increase in cumulative amounts of 5-26-fold in normal and hyperproliferative murine skin samples when compared to an ALA aqueous solution; and the ALA aqueous solution appeared less precise in terms of the penetration mode in hyperproliferative murine skin. After the ethosomes had been applied, the protoporphyrin IX (PpIX) intensity increased about 3.64-fold compared with that of the ALA aqueous solution, and the penetration depth reached 30-80 microm. The results demonstrated that the ethosomal carrier significantly improved the delivery of ALA and the formation of PpIX in both normal and hyperproliferative murine skin samples, and the expression level of tumor necrosis factor (TNF)-alpha was reduced after the ALA-ethosomes were applied to treat hyperproliferative murine skin. Furthermore, the results of present study encourage more investigations on the mechanism of the interaction with ethosomes and hyperproliferative murine skin.

  16. Topical delivery of 5-aminolevulinic acid-encapsulated ethosomes in a hyperproliferative skin animal model using the CLSM technique to evaluate the penetration behavior.

    PubMed

    Fang, Yi-Ping; Huang, Yaw-Bin; Wu, Pao-Chu; Tsai, Yi-Hung

    2009-11-01

    Psoriasis, an inflammatory skin disease, exhibits recurring itching, soreness, and cracked and bleeding skin. Currently, the topical delivery of 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) is an optional treatment for psoriasis which provides long-term therapeutic effects, is non-toxic and enjoys better compliance with patients. However, the precursor of ALA is hydrophilic, and thus its ability to penetrate the skin is limited. Also, little research has provided a platform to investigate the penetration behavior in disordered skin. We employed a highly potent ethosomal carrier (phosphatidylethanolamine; PE) to investigate the penetration behavior of ALA and the recovery of skin in a hyperproliferative murine model. We found that the application of ethosomes produced a significant increase in cumulative amounts of 5-26-fold in normal and hyperproliferative murine skin samples when compared to an ALA aqueous solution; and the ALA aqueous solution appeared less precise in terms of the penetration mode in hyperproliferative murine skin. After the ethosomes had been applied, the protoporphyrin IX (PpIX) intensity increased about 3.64-fold compared with that of the ALA aqueous solution, and the penetration depth reached 30-80 microm. The results demonstrated that the ethosomal carrier significantly improved the delivery of ALA and the formation of PpIX in both normal and hyperproliferative murine skin samples, and the expression level of tumor necrosis factor (TNF)-alpha was reduced after the ALA-ethosomes were applied to treat hyperproliferative murine skin. Furthermore, the results of present study encourage more investigations on the mechanism of the interaction with ethosomes and hyperproliferative murine skin. PMID:19660544

  17. Effective photoprotection of human skin against infrared A radiation by topically applied antioxidants: results from a vehicle controlled, double-blind, randomized study.

    PubMed

    Grether-Beck, Susanne; Marini, Alessandra; Jaenicke, Thomas; Krutmann, Jean

    2015-01-01

    Infrared A radiation (IRA) from solar sunlight contributes to photoaging of human skin, e.g. by upregulating MMP-1 expression in dermal fibroblasts, indicating the need for photoprotection of human skin against IRA. Up to now, however, there has been no controlled study to show that effective protection of human skin against IRA radiation is possible. Here, we have conducted a randomized, controlled, double-blinded prospective study in 30 healthy volunteers to assess the capacity of an SPF 30 sunscreen versus the same sunscreen supplemented with an antioxidant cocktail containing grape seed extract, vitamin E, ubiquinone and vitamin C to protect human skin against IRA radiation-induced MMP-1 upregulation. As expected, exposure to IRA radiation significantly upregulated MMP-1 expression, as compared to unirradiated skin, and this response was significantly reduced, if the SPF30 sunscreen plus the antioxidant cocktail had been applied prior to IRA radiation. In contrast, treatment of human skin with the SPF30 sunscreen alone did not provide significant protection. These results indicate that topically applied antioxidants effectively protect human skin against IRA radiation and that regular sunscreens need to be supplemented with specific antioxidants in order to achieve IRA photoprotection.

  18. Feasibility of measuring the bioavailability of topical ibuprofen in commercial formulations using drug content in epidermis and a methyl nicotinate skin inflammation assay.

    PubMed

    Treffel, P; Gabard, B

    1993-01-01

    A method has been developed which simultaneously compares the inhibition of an inflammation induced by a methyl nicotinate assay with the concentration of drug in the human epidermis determined in vitro following topical application of two 10% ibuprofen formulations. The bioavailability of drug from commercial gel and emulsion was assessed after the application of various doses (3, 6 and 12 mg/cm2) and an application time of 0.5 h at two time points: 0.5 and 24 h (only with the 12 mg/cm2 dose) after the removal of the non-steroidal anti-inflammatory drug (NSAID) from the skin. In parallel, we assessed the epidermal concentration of the drug in vitro and evaluated the anti-inflammatory effect of the topicals in vivo. A correlation (r = 0.9603, p < 0.001) between the amount of drug in the epidermis expressed as micrograms per milligram of epidermal protein and the corresponding inhibition of the inflammation was observed. Increasing the amount of drug in the epidermis correlated with an increased inhibition of the inflammation. The gel formulation released more drug to the skin and produced a greater anti-inflammatory effect. Topical NSAID concentration in treated skin can therefore be determined and correlates well with the resulting pharmacodynamic activity. This approach will likely have utility in optimizing topical NSAIDs.

  19. Topical application of a cleanser containing extracts of Diospyros kaki folium, Polygonum cuspidatum and Castanea crenata var. dulcis reduces skin oil content and pore size in human skin

    PubMed Central

    LEE, BO MI; AN, SUNGKWAN; KIM, SOO-YEON; HAN, HYUN JOO; JEONG, YU-JIN; LEE, KYOUNG-ROK; ROH, NAM KYUNG; AHN, KYU JOONG; AN, IN-SOOK; CHA, HWA JUN

    2015-01-01

    The effects of skin pores on skin topographic features can be reduced by decreasing excessive production and accumulation of sebum and elimination of comedones. Therefore, a cosmetic cleanser that regulates sebum homeostasis is required. In the present study, the effects of a cosmetic cleanser that contained Diospyros kaki folium, Polygonum cuspidatum and Castanea crenata var. dulcis (DPC) was examined on the removal of sebum and on skin pore size. Healthy volunteers (n=23) aged 20–50 years were asked to apply the test materials to the face. Skin oil content, pore size, pore number and extracted sebum surface area were measured using various measurement methods. All the measurements were performed at pre- and post-application of the test materials. When the cosmetic cleanser containing DPC was applied to the skin, the oil content decreased by 77.3%, from 6.19 to 1.40. The number of skin pores decreased by 24.83%, from 125.39 to 94.23. Skin pore size decreased from 0.07 to 0.02 µm3 (71.43% decrease). The amount of extracted sebum increased by 335% when the DPC cleanser was used. Compared to the control cleanser, skin oil content was significantly decreased when the cleanser that contained DPC was used. The cleanser containing DPC also decreased pore size and number. Finally, the DPC cleanser easily removed solidified sebum from the skin. PMID:26137233

  20. Evaluation of efficacy and tolerance of a nighttime topical antioxidant containing resveratrol, baicalin, and vitamin e for treatment of mild to moderately photodamaged skin.

    PubMed

    Farris, Patricia; Yatskayer, Margarita; Chen, Nannan; Krol, Yevgeniy; Oresajo, Christian

    2014-12-01

    Resveratrol is an effective anti-aging molecule with diverse biologic activity. It functions as a dual antioxidant that can neutralize free radicals and increase intrinsic antioxidant capacity. Additionally resveratrol increases mitochondrial biogenesis and has anti-inflammatory, anti-diabetic, and anti-cancer activity. In this paper we will focus on the use of topically applied resveratrol using a proprietary blend containing 1% resveratrol, 0.5% baicalin, and 1% vitamin E. This stabilized high concentration formulation demonstrates percutaneous absorption and alterations in gene expression such as hemoxygenase-1 (HO-1), vascular endothelial growth factor (VEGFA), and collagen 3 (COL3A1). Clinical assessment showed a statistically significant improvement in fine lines and wrinkles, skin firmness, skin elasticity, skin laxity, hyperpigmentation, radiance, and skin roughness over baseline in 12 weeks. Ultrasound measurements in the periorbital area showed an average improvement of 18.9% in dermal thickness suggesting significant dermal remodeling. These studies confirm that topical resveratrol, baicalin, and vitamin E are valuable ingredient that can be used for skin rejuvenation. PMID:25607790

  1. Evaluation of efficacy and tolerance of a nighttime topical antioxidant containing resveratrol, baicalin, and vitamin e for treatment of mild to moderately photodamaged skin.

    PubMed

    Farris, Patricia; Yatskayer, Margarita; Chen, Nannan; Krol, Yevgeniy; Oresajo, Christian

    2014-12-01

    Resveratrol is an effective anti-aging molecule with diverse biologic activity. It functions as a dual antioxidant that can neutralize free radicals and increase intrinsic antioxidant capacity. Additionally resveratrol increases mitochondrial biogenesis and has anti-inflammatory, anti-diabetic, and anti-cancer activity. In this paper we will focus on the use of topically applied resveratrol using a proprietary blend containing 1% resveratrol, 0.5% baicalin, and 1% vitamin E. This stabilized high concentration formulation demonstrates percutaneous absorption and alterations in gene expression such as hemoxygenase-1 (HO-1), vascular endothelial growth factor (VEGFA), and collagen 3 (COL3A1). Clinical assessment showed a statistically significant improvement in fine lines and wrinkles, skin firmness, skin elasticity, skin laxity, hyperpigmentation, radiance, and skin roughness over baseline in 12 weeks. Ultrasound measurements in the periorbital area showed an average improvement of 18.9% in dermal thickness suggesting significant dermal remodeling. These studies confirm that topical resveratrol, baicalin, and vitamin E are valuable ingredient that can be used for skin rejuvenation.

  2. Overlapping loss of heterozygosity by mitotic recombination on mouse chromosome 7F1-ter in skin carcinogenesis.

    PubMed Central

    Bianchi, A B; Navone, N M; Aldaz, C M; Conti, C J

    1991-01-01

    A significant role for mouse chromosome 7 abnormalities during chemically induced skin carcinogenesis has been advanced based on previous cytogenetic and molecular studies. To determine the frequency of allelic losses at different loci of chromosome 7 in skin tumors induced in the outbred SENCAR mouse stock by a two-stage initiation-promotion protocol, we compared the constitutional and tumor genotypes of premalignant papillomas and squamous cell carcinomas for loss of heterozygosity at different informative loci. In a previous study, these tumors had been analyzed for their allelic composition at the Harvey ras-1 (Ha-ras-1) locus and it was found that 39% of squamous cell carcinomas had lost the normal Ha-ras-1 allele exhibiting 3 or 2 copies of the mutated counterpart or gene amplification. In the present study, by combining Southern blot and polymerase chain reaction fragment length polymorphism analyses, we detected complete loss of heterozygosity at the beta-globin (Hbb) locus, distal to Ha-ras-1, in 15 of 20 (75%) skin carcinomas. In addition, 5 of 5 informative cases attained homozygosity at the int-2 locus, 27 centimorgans distal to Hbb. Polymerase chain reaction analysis of DNA extracted from papillomas devoid of stromal contamination by fluorescence-activated sorting of single cell dispersions immunolabeled with anti-keratin 13 antibody revealed loss of heterozygosity at the Hbb locus, demonstrating that this event occurs during premalignant stages of tumor development. Interestingly, loss of heterozygosity was only detected in late-stage lesions exhibiting a high degree of dysplasia and areas of microinvasion. Analysis of allelic ratios by densitometric scanning of tumors that had become homozygous at Hbb but retained heterozygosis at Ha-ras-1 indicated mitotic recombination as the mechanism underlying loss of heterozygosity on mouse chromosome 7 during chemically induced skin carcinogenesis. These findings are consistent with the presence of a putative

  3. An experimental double-blind irradiation study of a novel topical product (TPF 50) compared to other topical products with DNA repair enzymes, antioxidants, and growth factors with sunscreens: implications for preventing skin aging and cancer.

    PubMed

    Emanuele, Enzo; Spencer, James M; Braun, Martin

    2014-03-01

    The exposure to ultraviolet radiation (UVR) is a major risk factor for skin aging and the development of non-melanoma skin cancer (NMSC). Although traditional sunscreens remain the mainstay for the prevention of UVR-induced skin damage, they cannot ensure a complete protection against the whole spectrum of molecular lesions associated with UVR exposure. The formation of helix-distorting photoproducts such as cyclobutane pyrimidine dimers (CPD), as well as oxidative damage to DNA bases, including the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8OHdG) are among the key DNA lesions associated with photoaging and tumorigenesis. Besides DNA lesions, UVR-induced formation of free radicals can result in protein carbonylation (PC), a major form of irreversible protein damage that inactivates their biological function. This study compares a complex novel topical product (TPF50) consisting of three actives, ie, 1) traditional physical sunscreens (SPF 50), 2) a liposome-encapsulated DNA repair enzymes complex (photolyase, endonuclease, and 8-oxoguanine glycosylase [OGG1]), and 3) a potent antioxidant complex (carnosine, arazine, ergothionine) to existing products. Specifically, we assessed the ability of TFP50 vs those of DNA repair and antioxidant and growth factor topical products used with SPF 50 sunscreens in preventing CPD, 8OHdG, and PC formation in human skin biopsies after experimental irradiations. In head-to-head comparison studies, TPF50 showed the best efficacy in reducing all of the three molecular markers. The results indicated that the three TPF50 components had a synergistic effect in reducing CPD and PC, but not 8OHdG. Taken together, our results indicate that TPF50 improves the genomic and proteomic integrity of skin cells after repeated exposure to UVR, ultimately reducing the risk of skin aging and NMSC.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

    Denervated skin could result in impaired healing of wounds, such as decubitus ulcers and diabetic foot ulcers. Other studies indicated that cutaneous fiber density is reduced after inner nerve transection and that neuropeptide level depletes after denervation, leading to reduced cell proliferation around the wound and thus wound healing problems. Recent studies have revealed that skin-derived precursors (SKPs), which form a neural crest-related stem cell population in the dermis of skin, participate in cutaneous nerve regeneration. We hypothesized that injecting SKPs into denervated wound promotes healing. A bilateral denervation wound model was established followed by SKP transplantation. The wound healing rate was determined at 7, 14, and 21 d after injury. Cell proliferation activity during wound healing was analyzed by proliferating cell nuclear antigen immunohistochemistry (IHC). Nerve fiber density was measured by S-100 IHC. The contents of nerve growth factor, substance P, and calcitonin gene-related peptide were examined by enzyme-linked immunosorbent assay. The rate of epithelization in the SKP-treated group was faster than that in the control group. Wound cell proliferation and nerve fiber density were obviously higher in the SKP-treated group than in the control group. In addition, the content of neuropeptides was higher in the SKP-treated group than in the control group during wound healing. In conclusion, SKPs can promote denervated wound healing through cell proliferation and nerve fiber regeneration, and can facilitate the release of neuropeptides. PMID:26045771

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

    PubMed Central

    Nickoloff, B. J.; Kunkel, S. L.; Burdick, M.; Strieter, R. M.

    1995-01-01

    Research into the cause and pathophysiological mechanisms underlying expression of psoriatric skin lesions has been hampered by lack of an appropriate animal model for this common and enigmatic cutaneous disease. These studies characterize normal skin, pre-psoriatic skin, and psoriatic plaque skin samples transplanted onto severe combined immunodeficiency mice. In this report we document that 1), normal, prepsoriatic, and psoriatic plaque keratome skin samples can be transplanted onto severe combined immunodeficiency mice reliably with high rates of graft survival (> 85%) and with reproducible changes consistently observed over prolonged periods of engraftment; 2), after transplantation, by clinical assessment and routine light microscopy, normal skin remained essentially normal whereas pre-psoriatic skin became thicker, and psoriatic plaque skin retained its characteristic plaque-type elevation and scale; 3), by using a panel of antibodies and immunohistochemical analysis, the overall phenotype of human cell types (including immunocytes) that persisted in the transplanted skin was remarkably similar to the immunophenotype of pretransplanted skin samples; 4), clearly recognized interface zones between human and murine skin within the epidermal and dermal compartments could be identified by routine microscopy and immunostaining, with focal areas of chimerism; and 5), elevated interleukin 8 cytokine levels were present in transplanted pre-psoriatic and psoriatic plaque skin samples. We conclude that there are many similarities between pre- and post-transplanted human samples of normal and psoriatic skin that are grafted onto severe combined immunodeficiency mice. Thus, we propose that this new animal model is appropriate for additional mechanistic-type studies designed to reveal the underlying genetic/etiological abnormality, as well as better illuminate the pathophysiological basis, for this important skin disease. Images Figure 1 Figure 2 Figure 3 PMID:7887440

  7. The Effects of Topically Applied Glycolic Acid and Salicylic Acid on Ultraviolet Radiation-Induced Erythema, DNA Damage and Sunburn Cell Formation in Human Skin

    PubMed Central

    Kornhauser, Andrija; Wei, Rong-Rong; Yamaguchi, Yuji; Coelho, Sergio G.; Kaidbey, Kays; Barton, Curtis; Takahashi, Kaoruko; Beer, Janusz Z.; Miller, Sharon A.; Hearing, Vincent J.

    2009-01-01

    Background α-Hydroxy acids (αHA) are reported to reduce signs of aging in the skin and are widely used cosmetic ingredients. Several studies suggest that αHA can increase the sensitivity of skin to ultraviolet radiation. More recently, β-hydroxy acids (βHA), or combinations of αHA and βHA have also been incorporated into antiaging skin care products. Concerns have also arisen about increased sensitivity to ultraviolet radiation following use of skin care products containing β-HA. Objective To determine whether topical treatment with glycolic acid, a representative αHA, or with salicylic acid, a βHA, modifies the short-term effects of solar simulated radiation (SSR) in human skin. Methods Fourteen subjects participated in this study. Three of the four test sites on the mid-back of each subject were treated daily Monday - Friday, for a total of 3.5 weeks, with glycolic acid (10%), salicylic acid (2%), or vehicle (control). The fourth site received no treatment. After the last treatment, each site was exposed to SSR, and shave biopsies from all 4 sites were obtained. The endpoints evaluated in this study were erythema (assessed visually and instrumentally), DNA damage and sunburn cell formation. Results Treatment with glycolic acid resulted in increased sensitivity of human skin to SSR, measured as an increase in erythema, DNA damage and sunburn cell formation. Salicylic acid did not produce significant changes in any of these biomarkers. Conclusions Short-term topical application of glycolic acid in a cosmetic formulation increased the sensitivity of human skin to SSR, while a comparable treatment with salicylic acid did not. PMID:19411163

  8. FATAL KERATOMAS DUE TO DEEP HOMOGRAFTS OF THE BENIGN PAPILLOMAS OF TARRED MOUSE SKIN

    PubMed Central

    Rous, Peyton; Allen, Raymond A.

    1958-01-01

    enlarging, fluid-filled cyst forms, with walls that are bare except where a stalked or cauliflower papilloma exists, projecting inwards. At last the cyst ruptures and a second dissecting cyst forms, also devoid of papilloma tissue; or else the overlying skin undergoes pressure necrosis, the cyst fluid escapes through a rent, and fatal infection ensues. All gradations exist between Type A and Type C. The cancers derivative from both exhibit a marked disability,—though invasive they are almost or quite unable to extend along bare connective tissue. The papillomas that are possessed of this faculty spread beyond them along the cyst wall, and kill the host through their unceasing activity. In collateral work a papilloma was transplanted that was found protruding from the external auditory canal of a mouse which had received an intramuscular injection of methylcholanthrene many months previously. The tumor is now in its 5th generation, after 15 months. The growths it forms are of Type A. All of the papillomas are functioning tumors, with their own cells as the functioning product. Their papilliferous shape, when on the skin, is due solely to inability of their cells to gain space in other ways. Intrinsically they are keratomas. The papillomas do well after transfer to deep situations because the growth of their cells is indirectly promoted, through favoring local conditions. No direct promotion takes place like that when the cells of prostatic and mammary tumors are stimulated to multiply by hormones. Doubtless many agents act in both ways, that is to say by dual promotion. PMID:13481256

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

    NASA Technical Reports Server (NTRS)

    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.

  10. EPR/spin-label technique as an analytical tool for determining the resistance of reactive topical skin protectants (rTSPs) to the breakthrough of vesicant agents.

    PubMed

    Arroyo, C M; Janny, S J

    1995-04-01

    Ointment formulations of reactive topical skin protectants (rTSPs) or topical skin protectants (TSPs) based on perfluorinated polyether material (PFPE, i.e., fomblin RT-15) were prepared and spin labeled. Four N-oxyl-4-4'-dimethyloxazolidine derivatives of stearic acid, 5-NS, 7-NS, 12-NS, and 16-NS, were used as spin probes. The spin-labeled vehicle, fomblin-RT-15, and vehicle containing chloroamide (S-330, an antivesicant) were exposed to various concentrations of half-mustard gas. The order parameter (S) was dependent on the depth of penetration of the paramagnetic group into the vehicle (fomblin) and on the chemical composition of the reactive antivesicant under investigation. The net change of the viscosity of the vehicle and the chemical composition were seen to affect the penetration profile. This will provide a useful in vitro screening technique to develop antivesicant TSPs.

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

    PubMed

    Dillon, Lloye M; Hida, Aline; Garcia, Sofia; Prolla, Tomas A; Moraes, Carlos T

    2012-01-01

    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.

  12. Three-dimensional laser-induced photoacoustic tomography of mouse brain with the skin and skull intact

    NASA Astrophysics Data System (ADS)

    Wang, Xueding; Pang, Yongjiang; Ku, Geng; Stoica, George; Wang, Lihong V.

    2003-10-01

    Three-dimensional laser-induced photoacoustic tomography, also referred to as optoacoustic tomography, is developed to image animal brain structures noninvasively with the skin and skull intact. This imaging modality combines the advantages of optical contrast and ultrasonic resolution. The distribution of optical absorption in a mouse brain is imaged successfully. The intrinsic optical contrast reveals not only blood vessels but also other detailed brain structures, such as the cerebellum, hippocampus, and ventriculi lateralis. The spatial resolution is primarily diffraction limited by the received photoacoustic waves. Imaged structures of the brain at different depths match the corresponding histological pictures well.

  13. Light Fractionation Significantly Increases the Efficacy of Photodynamic Therapy Using BF-200 ALA in Normal Mouse Skin

    PubMed Central

    de Bruijn, Henriëtte S.; Brooks, Sander; van der Ploeg-van den Heuvel, Angélique; ten Hagen, Timo L. M.; de Haas, Ellen R. M.; Robinson, Dominic J.

    2016-01-01

    Background Light fractionation significantly increases the efficacy of 5-aminolevulinic acid (ALA) based photodynamic therapy (PDT) using the nano-emulsion based gel formulation BF-200. PDT using BF-200 ALA has recently been clinically approved and is under investigation in several phase III trials for the treatment of actinic keratosis. This study is the first to compare BF-200 ALA with ALA in preclinical models. Results In hairless mouse skin there is no difference in the temporal and spatial distribution of protoporphyrin IX determined by superficial imaging and fluorescence microscopy in frozen sections. In the skin-fold chamber model, BF-200 ALA leads to more PpIX fluorescence at depth in the skin compared to ALA suggesting an enhanced penetration of BF-200 ALA. Light fractionated PDT after BF-200 ALA application results in significantly more visual skin damage following PDT compared to a single illumination. Both ALA formulations show the same visual skin damage, rate of photobleaching and change in vascular volume immediately after PDT. Fluorescence immunohistochemical imaging shows loss of VE-cadherin in the vasculature at day 1 post PDT which is greater after BF-200 ALA compared to ALA and more profound after light fractionation compared to a single illumination. Discussion The present study illustrates the clinical potential of light fractionated PDT using BF-200 ALA for enhancing PDT efficacy in (pre-) malignant skin conditions such as basal cell carcinoma and vulval intraepithelial neoplasia and its application in other lesion such as cervical intraepithelial neoplasia and oral squamous cell carcinoma where current approaches have limited efficacy. PMID:26872051

  14. In vivo skin absorption dynamics of topically applied pharmaceuticals monitored by fiber-optic diffuse reflectance spectroscopy

    NASA Astrophysics Data System (ADS)

    Kim, Ki-Hong; Jheon, Sanghoon; Kim, Jong-Ki

    2007-03-01

    A simple non-invasive ultra-violet/visible (UV/vis) diffusive reflectance spectroscopy combined with fiber-optics was investigated to elicit the dynamics of skin penetration in vivo of a pharmaceutical, aminolevulinic acid polyethylene glycol cream (5-ALA-PEG cream). Temporal data of the reflectance, R( λ), were measured from a bare skin region and from a skin region treated with 5-ALA cream. The difference in apparent optical density [(ΔAOD) = Δ log[1/ R( λ)

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

    PubMed

    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

  16. Diffuse Optical Spectroscopy for the Quantitative Assessment of Acute Ionizing Radiation Induced Skin Toxicity Using a Mouse Model

    PubMed Central

    Chin, Lee; Korpela, Elina; Kim, Anthony; Yohan, Darren; Niu, Carolyn; Wilson, Brian C.; Liu, Stanley K.

    2016-01-01

    Acute skin toxicities from ionizing radiation (IR) are a common side effect from therapeutic courses of external beam radiation therapy (RT) and negatively impact patient quality of life and long term survival. Advances in the understanding of the biological pathways associated with normal tissue toxicities have allowed for the development of interventional drugs, however, current response studies are limited by a lack of quantitative metrics for assessing the severity of skin reactions. Here we present a diffuse optical spectroscopic (DOS) approach that provides quantitative optical biomarkers of skin response to radiation. We describe the instrumentation design of the DOS system as well as the inversion algorithm for extracting the optical parameters. Finally, to demonstrate clinical utility, we present representative data from a pre-clinical mouse model of radiation induced erythema and compare the results with a commonly employed visual scoring. The described DOS method offers an objective, high through-put evaluation of skin toxicity via functional response that is translatable to the clinical setting. PMID:27284926

  17. An inducible mouse model for skin cancer reveals distinct roles for gain- and loss-of-function p53 mutations

    PubMed Central

    Caulin, Carlos; Nguyen, Thao; Lang, Gene A.; Goepfert, Thea M.; Brinkley, Bill R.; Cai, Wei-Wen; Lozano, Guillermina; Roop, Dennis R.

    2007-01-01

    Mutations in ras and p53 are the most prevalent mutations found in human nonmelanoma skin cancers. Although some p53 mutations cause a loss of function, most result in expression of altered forms of p53, which may exhibit gain-of-function properties. Therefore, understanding the consequences of acquiring p53 gain-of-function versus loss-of-function mutations is critical for the generation of effective therapies for tumors harboring p53 mutations. Here we describe an inducible mouse model in which skin tumor formation is initiated by activation of an endogenous K-rasG12D allele. Using this model we compared the consequences of activating the p53 gain-of-function mutation p53R172H and of deleting the p53 gene. Activation of the p53R172H allele resulted in increased skin tumor formation, accelerated tumor progression, and induction of metastasis compared with deletion of p53. Consistent with these observations, the p53R172H tumors exhibited aneuploidy associated with centrosome amplification, which may underlie the mechanism by which p53R172H exerts its oncogenic properties. These results clearly demonstrate that p53 gain-of-function mutations confer poorer prognosis than loss of p53 during skin carcinogenesis and have important implications for the future design of therapies for tumors that exhibit p53 gain-of-function mutations. PMID:17607363

  18. p53-independent apoptosis in UV-irradiated mouse skin: possible inhibition by 50 Hz magnetic fields.

    PubMed

    Kumlin, Timo; Heikkinen, Päivi; Kosma, Veli-Matti; Alhonen, Leena; Jänne, Juhani; Juutilainen, Jukka

    2002-06-01

    Our recent results suggest that 50 Hz magnetic fields (MF) enhance ultraviolet (UV)-induced tumorigenesis in mouse skin. The aim of the present experiment was to study suppression of apoptosis as a possible mechanism for MF effects on skin tumorigenesis. Another aim was to test the importance of a UV and MF exposure schedule, particularly the role of MF exposure prior to UV irradiation. Female mice were exposed to a UV dose of 2 human MED and to 100 microT MF of 50 Hz, using the following exposure schedules: group 1 sham MF 24 h, UV 1 h, sham MF 24 h; group 2 sham MF 24 h, UV 1 h, MF 24 h; group 3 MF 24 h, UV 1 h, MF 24 h. Lamps emitting simulated solar radiation (SSR) were used for UV irradiation. Skin samples were analysed for apoptosis, expression of the p53 gene, activity of the enzyme ornithine decarboxylase (ODC) and polyamine concentrations. A significantly (p = 0.017) lower number of apoptotic cells was measured in group 2 compared to group 1. A similar but not statistically significant (p = 0.064) decrease was also detected in group 3. No p53 expression was detected in any sample. The levels of ODC and putrescine did not differ significantly between the UV-only and UV and MF-exposed groups. Spermidine and spermine levels were significantly (p = 0.014 and 0.014, respectively) lower in group 3 than in group 1, but no decrease was observed in group 2. Our findings suggest that SSR induces p53-independent apoptosis in mouse skin and that the apoptotic response may be inhibited by exposure to MF. The exposure schedule did not alter the MF effect. The results do not support a causal role for polyamines in MF effects on apoptosis.

  19. Resveratrol and Black Tea Polyphenol Combination Synergistically Suppress Mouse Skin Tumors Growth by Inhibition of Activated MAPKs and p53

    PubMed Central

    George, Jasmine; Singh, Madhulika; Srivastava, Amit Kumar; Bhui, Kulpreet; Roy, Preeti; Chaturvedi, Pranav Kumar; Shukla, Yogeshwer

    2011-01-01

    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. PMID:21887248

  20. 21 CFR 878.4011 - Tissue adhesive with adjunct wound closure device for topical approximation of skin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY... approximated skin edges of wounds from surgical incisions, including punctures from minimally invasive...

  1. 21 CFR 878.4011 - Tissue adhesive with adjunct wound closure device for topical approximation of skin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY... approximated skin edges of wounds from surgical incisions, including punctures from minimally invasive...

  2. 21 CFR 878.4011 - Tissue adhesive with adjunct wound closure device for topical approximation of skin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY... approximated skin edges of wounds from surgical incisions, including punctures from minimally invasive...

  3. 21 CFR 878.4011 - Tissue adhesive with adjunct wound closure device for topical approximation of skin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY... approximated skin edges of wounds from surgical incisions, including punctures from minimally invasive...

  4. Effect of topical vasoconstrictor exposure upon tumoricidal radiotherapy.

    PubMed

    Fahl, William E

    2014-08-15

    Topical application of the alpha adrenergic vasoconstrictors norepinephrine, phenylephrine or epinephrine to skin or mucosa in alcohol:water-based delivery vehicles minutes before irradiation has recently been shown to protect skin and mucosa cells against radiotherapy-induced toxicities in both preclinical and clinical studies. The protective mechanism is thought to involve transient skin or mucosal vasoconstriction with secondary, transient hypoxia and associated radioprotection. Regarding possible protection of tumor cell nests within the radiotherapy field, the endothelial cell-abnormal stroma constructed blood vessels generally found in human tumors commonly lack adrenergic receptor-containing smooth muscle cells that are required to achieve vasoconstriction. Consistent with this, we show here that topical application of norepinephrine or phenylephrine to broken or intact skin over human Cal-27 or A-431 xeonograft, or mouse solid L1210 allograft tumors growing subcutaneously in nude mice, showed no effect upon radiation-induced tumor growth inhibition. Although vasoconstrictor-induced nude mouse skin blanch was seen minutes after topical application of 600 mM norepinephrine, no blanching was seen within the A-431 xenograft tumors. Radiation dermatitis was severe 11 days post-irradiation (2 × 13.8 Gy) in the irradiated field containing xenograft tumors in mice that received topical delivery vehicle, but was absent in mice that received topical norepinephrine. Topical vasoconstrictor-conferred prevention of radiation dermatitis without discernible radioprotection of three histologically diverse xenograft or allograft tumors supports further development of the topical vasoconstrictor therapeutic strategy in humans.

  5. Prediction of formulation effects on dermal absorption of topically applied ectoparasiticides dosed in vitro on canine and porcine skin using a mixture-adjusted quantitative structure permeability relationship.

    PubMed

    Riviere, J E; Brooks, J D; Collard, W T; Deng, J; de Rose, G; Mahabir, S P; Merritt, D A; Marchiondo, A A

    2014-10-01

    Topical application of ectoparasiticides for flea and tick control is a major focus for product development in animal health. The objective of this work was to develop a quantitative structure permeability relationship (QSPeR) model sensitive to formulation effects for predicting absorption and skin deposition of five topically applied drugs administered in six vehicle combinations to porcine and canine skin in vitro. Saturated solutions (20 μL) of (14) C-labeled demiditraz, fipronil, permethrin, imidacloprid, or sisapronil were administered in single or binary (50:50 v/v) combinations of water, ethanol, and transcutol (6 formulations, n = 4-5 replicates per treatment) nonoccluded to 0.64 cm(2) disks of dermatomed pig or dog skin mounted in flow-through diffusion cells. Perfusate flux over 24 h and skin deposition at termination were determined. Permeability (logKp), absorption, and penetration endpoints were modeled using a four-term Abrahams and Martin (hydrogen-bond donor acidity and basicity, dipolarity/polarizability, and excess molar refractivity) linear free energy QSPeR equation with a mixture factor added to compensate for formulation ingredient interactions. Goodness of fit was judged by r(2) , cross-validation coefficient, coefficients (q(2) s), and Williams Plot to visualize the applicability domain. Formulation composition was the primary determinant of permeation. Compounds generally penetrated dog skin better than porcine skin. The vast majority of permeated penetrant was deposited within the dosed skin relative to transdermal flux, an attribute for ectoparasiticides. The best QSPeR logKp model for pig skin permeation (r(2) = 0.86, q(2) s = 0.85) included log octanol/water partition coefficient as the mixture factor, while for dogs (r(2) = 0.91, q(2) s = 0.90), it was log water solubility. These studies clearly showed that the permeation of topical ectoparasiticides could be well predicted using QSPeR models that account for both the physical

  6. Evaluation of haemoglobin changes of skin and muscle tissue of the calf induced by topical application of a nonivamide / nicoboxil cream

    NASA Astrophysics Data System (ADS)

    Warnecke, Jan; Wendt, Thomas; Schak, Matthias; Schiffer, Thorsten; Bloch, Wilhelm; Kohl-Bareis, Matthias

    2011-07-01

    Topical agents inducing hyperaemisation like nonivamide or nicoboxil increase cutaneous blood flow and temperature and induce erythema. It is not proven up to now whether there is also a hyperaemisation effect in skeletal muscle. This study has the objective to determine the effects of a nonivamide / nicoboxil cream on haemodynamics in skin and calf muscle via optical spectroscopy in the visible and near-infrared with a separation of changes for skin and muscle. Left and right calves of 14 healthy subjects were treated with a nonivamide / nicoboxil cream or mock administration, and cutaneous and muscle haemoglobin were measured using a combined NIRS / VIS sensor. The topical application of the cream increased the concentration of oxygenated haemoglobin and tissue oxygen saturation significantly in skin as well as in muscle of the treated legs already after 15 minutes, with stronger and faster effects in skin. In contrast, the change in deoxygenated haemoglobin was found to be small. The kinetic of all changes varied widely between the subjects. The found haemoglobin changes might explain the beneficial effect of hyperaemisation creams for the treatment of minor injuries.

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

    EPA Science Inventory

    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...

  8. Skin (Pressure) Sores

    MedlinePlus

    ... Topic Skin dryness Next Topic Sleep problems Skin (pressure) sores A skin or pressure sore develops when the blood supply to an ... is bedridden or always in a wheelchair puts pressure on the same places much of the time. ...

  9. Topical hydrocortisone 17-butyrate 21-propionate in the treatment of inflammatory skin diseases: pharmacological data, clinical efficacy, safety and calculation of the therapeutic index.

    PubMed

    Fölster-Holst, R; Abeck, D; Torrelo, A

    2016-03-01

    Hydrocortisone 17-butyrate 21-propionate (hydrocortisone buteprate, HBP) is a medium potent, non-halogenated double-ester of hydrocortisone with a favorable benefit/risk ratio for the treatment of inflammatory skin disorders. HBP is available as a 0.1% cream or ointment formulation. Good results were obtained with a once-daily topical treatment. HBP is characterized by a strong topical anti-inflammatory activity and weak systemic action. It is considered to have potency comparable to that of betamethasone 17-valerate (BV), but its systemic effects are less pronounced. HBP was shown to have a good efficacy in the treatment of various oozing and lichenified eczematous skin diseases including atopic dermatitis (AD) and in the treatment of psoriasis vulgaris. Even in very young children, HBP proved successful as an effective and safe drug. A therapeutic index of 2.0 can be attributed to this glucocorticoid. In this respect, there is no difference between topical HBP and other topical glucocorticoids with increased benefit/risk ratio, e.g. prednicarbate (PC), methylprednisolone aceponate (MPA) and mometasone furoate (MM). PMID:27183704

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

    PubMed

    Ili, Pinar

    2016-07-01

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

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

    PubMed

    Ili, Pinar

    2016-07-01

    Exposure to UV radiation can cause histopathological and ultrastructural changes in the skin. Origanum hypericifolium, an endemic Turkish plant,essential oil is mainly composed of monoterpenes. The effects of undiluted O. hypericifolium oil on the ultrastructural characteristics of the UVB-irradiated dorsal skin of mice were investigated using transmission electron microscopy. The BALB/c mice were shaved of dorsal hair and randomly housed into 4 groups: 1: control; 2: UVB-irradiated; 3: oil applied; and 4: oil applied and UVB-irradiated. The oil was applied topically to the dorsal skins of the mice on alternate days for 1week prior to UVB exposure. The skins were irradiated for a total dose of 3.5J/cm(2). The sections were stained with hematoxylin and eosin, semithin sections were stained with toluidine blue and ultrathin sections were contrasted with uranyl acetate/lead citrate. There were histopathological changes such as parakeratosis and squamous hyperplasia in the epidermal cell layers (Groups 3 and 4). There were also ultrastructural changes including lacunae formations throughout the stratum corneum layer (Groups 2, 3, and 4), enlargement of intercellular spaces (Groups 2 and 3), reduced desmosomes, narrow and elongated interdigitations, shortened, relatively indistinct and electron dense intermediate keratin filament bundles (Group 3). There were various sizes of cytoplasmic and perinucleolar vacuoles (Groups 3 and 4) and apoptotic bodies phagocytized by keratinocytes (Group 4). I conclude that undiluted oil has side-effects and the potential to inflict injury to the skin. The oil does not ameliorate the negative effects of UVB on epidermal skin cells. PMID:27156161

  12. Berteroin present in cruciferous vegetables exerts potent anti-inflammatory properties in murine macrophages and mouse skin.

    PubMed

    Jung, Yoo Jin; Jung, Jae In; Cho, Han Jin; Choi, Myung-Sook; Sung, Mi-Kyung; Yu, Rina; Kang, Young-Hee; Park, Jung Han Yoon

    2014-11-11

    Berteroin (5-methylthiopentyl isothiocyanate) is a sulforaphane analog present in cruciferous vegetables, including Chinese cabbage, rucola salad leaves, and mustard oil. We examined whether berteroin exerts anti-inflammatory activities using lipopolysaccharide (LPS)-stimulated Raw 264.7 macrophages and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse skin inflammation models. Berteroin decreased LPS-induced release of inflammatory mediators and pro-inflammatory cytokines in Raw 264.7 macrophages. Berteroin inhibited LPS-induced degradation of inhibitor of κBα (IκBα) and nuclear factor-κB p65 translocation to the nucleus and DNA binding activity. Furthermore, berteroin suppressed degradation of IL-1 receptor-associated kinase and phosphorylation of transforming growth factor β activated kinase-1. Berteroin also inhibited LPS-induced phosphorylation of p38 MAPK, ERK1/2, and AKT. In the mouse ear, berteroin effectively suppressed TPA-induced edema formation and down-regulated iNOS and COX-2 expression as well as phosphorylation of AKT and ERK1/2. These results demonstrate that berteroin exhibits potent anti-inflammatory properties and suggest that berteroin can be developed as a skin anti-inflammatory agent.

  13. Time course of lewisite-induced skin lesions and inflammatory response in the SKH-1 hairless mouse model.

    PubMed

    Nguon, Nina; Cléry-Barraud, Cécile; Vallet, Virginie; Elbakdouri, Nacéra; Wartelle, Julien; Mouret, Stéphane; Bertoni, Marine; Dorandeu, Frédéric; Boudry, Isabelle

    2014-01-01

    Data on the toxicity of lewisite (L), a vesicant chemical warfare agent, are scarce and conflicting, and the use of the specific antidote is not without drawbacks. This study was designed to evaluate if the SKH-1 hairless mouse model was suitable to study the L-induced skin injuries. We studied the progression of lesions following exposure to L vapors for 21 days using paraclinical parameters (color, transepidermal water loss (TEWL), and biomechanical measurements), histological assessments, and biochemical indexes of inflammation. Some data were also obtained over 27 weeks. The development of lesions was similar to that reported in other models. The TEWL parameter appeared to be the most appropriate index to follow their progression. Histological analysis showed inflammatory cell infiltration and microvesications at day 1 and a complete wound closure by day 21. Biochemical studies indicated a deregulation of the levels of several cytokines and receptors involved in inflammation. An increase in the quantity of pro-matrix metalloproteinases 2 and 9 was shown as observed in other models. This suggests that the SKH-1 mouse model is relevant for the investigation of the physiopathological process of skin lesions induced by L and to screen new treatment candidates. PMID:24635178

  14. Studies on the relationship between epidermal cell turnover kinetics and permeability of hairless mouse skin

    SciTech Connect

    Han, S.R.

    1988-01-01

    The primary aim of this study was to develop non-invasive, physical means to quantitatively assess the epidermal turnover kinetics and barrier properties of the skin and relate these to the cutaneous irritation which results from ultraviolet light irradiation and mold thermal burns. After systematically injecting radiolabeled glycine, the appearance of radioactivity at the skin's surface indicated the transit time of radiolabeled cells through the skin. By plotting the data as the cumulative specific activity against time and then fitting them with a third order polynomial equation, it is possible to estimate the turnover time of the stratum corneum. The skin turnover was coordinated with non-invasive transepidermal water loss (TEWL) studies determined with an evaporimeter. In vitro diffusion studies of the permeability of hydrocortisone through UVB irradiated and thermally burned skin were also performed. The studies indicated that irritated skin offers a relatively low diffusional resistance to hydrocortisone. Depending on the severity of the trauma, the increases in hydrocortisone's permeability coefficient through irritated skin ranged from a low of about 2 times normal to a high of about 210 times normal. Trauma-induced changes in hydrocortisone permeability parallel changes in TEWL, proving that the barrier deficient state resulting from rapid epidermal turnover is a general phenomenon.

  15. Transgenic overexpression of transforming growth factor alpha bypasses the need for c-Ha-ras mutations in mouse skin tumorigenesis.

    PubMed Central

    Vassar, R; Hutton, M E; Fuchs, E

    1992-01-01

    The induction of skin papillomas in mice can be divided into two different stages. Chemical initiation frequently elicits mutations in the Ha-ras gene, leading to the constitutive activation of ras. The second step, promotion, involves repetitive topical application of phorbol esters or wounding, leading to epidermal hyperproliferation and papilloma formation. We have found that overexpression of transforming growth factor alpha (TGF-alpha) in the basal epidermal layer of transgenic mice yielded papillomas directly upon wounding or 12-O-tetradecanoylphorbol-13-acetate treatment without the need for an initiator. Moreover, papillomas from TGF-alpha mice did not exhibit mutations in the Ha-ras gene. Interestingly, TGF-alpha acted synergistically with 12-O-tetradecanoylphorbol-13-acetate to enhance epidermal hyperproliferation. Our results demonstrate a central role for TGF-alpha overexpression in tumorigenesis and provide an important animal model for the study of skin tumorigenesis. Images PMID:1406654

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

    PubMed

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

    2015-10-01

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

  17. RNAi mediated IL-6 in vitro knockdown in psoriasis skin model with topical siRNA delivery system based on liquid crystalline phase.

    PubMed

    Depieri, Lívia Vieira; Borgheti-Cardoso, Lívia Neves; Campos, Patrícia Mazureki; Otaguiri, Katia Kaori; Vicentini, Fabiana Testa Moura de Carvalho; Lopes, Luciana Biagini; Fonseca, Maria José Vieira; Bentley, M Vitória Lopes Badra

    2016-08-01

    Gene therapy by RNA interference (RNAi) is a post-transcriptional silencing process that can suppress the expression of a particular gene and it is a promising therapeutic approach for the treatment of many severe diseases, including cutaneous disorders. However, difficulties related to administration and body distribution limit the clinical use of small interfering RNA (siRNA) molecules. In this study, we proposed to use nanocarriers to enable siRNA application in the topical treatment of skin disorders. A siRNA nanodispersion based on liquid crystalline phase and composed of monoolein (MO), oleic acid (OA) and polyethylenimine (PEI) was developed and its physicochemical properties, efficiency of complexation and carrier/siRNA stability were assessed. Subsequently, cell viability, cellular uptake, in vitro skin irritation test using reconstructed human epidermis (RHE) and in vitro IL-6 knockdown in psoriasis skin model were evaluated. The results showed that the liquid crystalline nanodispersion is a promising topical delivery system for administration of siRNA, being able to overcome the limitations of the route of administration, as well those resulting from the characteristics of siRNA molecules. The formulation was effective at complexing the siRNA, presented high rate of cell uptake (∼90%), increased the skin penetration of siRNA in vitro, and did not cause skin irritation compared with Triton-X (a moderate irritant), resulting in a 4-fold higher viability of reconstructed human epidermis and a 15.6-fold lower release of IL-1α. A single treatment with the liquid crystalline nanodispersion carrying IL-6 siRNA for 6h was able to reduce the extracellular IL-6 levels by 3.3-fold compared with control treatment in psoriasis skin model. Therefore, liquid crystalline nanodispersion is a suitable nanocarrier for siRNA with therapeutic potential to suppress skin disease-specific genes. This study also highlights the applicability of reconstructed skin models in

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

    PubMed

    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

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

    PubMed

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

    1997-12-01

    The potential use of terpenes/terpenoids as penetration enhancers in the transdermal delivery of propranolol hydrochloride (PL) was investigated. PL was chosen for the reasons of its extensive first-pass metabolism and short elimination half-life. The terpenes studied included L-menthol, (+)-limonene, (+/-)-linalool, and carvacrol at 1%, 5%, and 10% w/v concentrations. The diffusion of PL across excised hairless mouse skin was determined using side-by-side diffusion cells. Flux, permeability coefficient (Pm), and lag time (tL) were calculated. PL showed comparable lag times with menthol at all three concentration levels. At a 1% level of carvacrol, PL exhibited a 2.4- and 2.2-fold increase in lag time compared with 5 and 10% levels of enhancer, respectively. In the presence of limonene, PL had shown maximum lag time (between 3.0 and 3.3 h) at all three levels. In the case of linalool, the lag times for PL with 5 and 10% levels of enhancer were 7.0- and 5.2-fold less compared with 1% level. A significant (p < 0.05) concentration effect was observed only with linalool. Hydrogel-based patches were formulated with or without menthol as enhancer. Release profiles from the hydrogel formulations obeyed zero-order kinetics. The permeability of propranolol was significantly higher (p < 0.05) from the test patch than the control (no enhancer) patch across the mouse skin. The mechanism of permeation enhancement of menthol could involve its distribution preferentially into the intercellular spaces of stratum corneum and the possible reversible disruption of the intercellular lipid domain. The results suggest the potential use of menthol as effective penetration enhancer in the delivery of significant amounts of PL through skin. PMID:9423148

  20. A Novel Nude Mouse Model of Hypertrophic Scarring Using Scratched Full Thickness Human Skin Grafts

    PubMed Central

    Alrobaiea, Saad M.; Ding, Jie; Ma, Zengshuan; Tredget, Edward E.

    2016-01-01

    Objective: Hypertrophic scar (HTS) is a dermal form of fibroproliferative disorder that develops following deep skin injury. HTS can cause deformities, functional disabilities, and aesthetic disfigurements. The pathophysiology of HTS is not understood due to, in part, the lack of an ideal animal model. We hypothesize that human skin with deep dermal wounds grafted onto athymic nude mice will develop a scar similar to HTS. Our aim is to develop a representative animal model of human HTS. Approach: Thirty-six nude mice were grafted with full thickness human skin with deep dermal scratch wound before or 2 weeks after grafting or without scratch. The scratch on the human skin grafts was made using a specially designed jig that creates a wound >0.6 mm in depth. The xenografts were morphologically analyzed by digital photography. Mice were euthanized at 1, 2, and 3 months postoperatively for histology and immunohistochemistry analysis. Results: The mice developed raised and firm scars in the scratched xenografts with more contraction, increased infiltration of macrophage, and myofibroblasts compared to the xenografts without deep dermal scratch wound. Scar thickness and collagen bundle orientation and morphology resembled HTS. The fibrotic scars in the wounded human skin were morphologically and histologically similar to HTS, and human skin epithelial cells persisted in the remodeling tissues for 1 year postengraftment. Innovation and Conclusions: Deep dermal injury in human skin retains its profibrotic nature after transplantation, affording a novel model for the assessment of therapies for the treatment of human fibroproliferative disorders of the skin. PMID:27366591

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

    PubMed Central

    Cao Minh, Trinh; Xuan Hai, Do; Thi Ngoc, Pham

    2015-01-01

    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. PMID:25722887

  2. Effects of intense pulsed light on tissue vascularity and wound healing: a study with mouse island skin flap model.

    PubMed

    Cao Minh, Trinh; Xuan Hai, Do; Thi Ngoc, Pham

    2015-01-01

    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/cm(2), 25 J/cm(2), and 15 J/cm(2) 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.

  3. Comparative histologic effects of daily topical application of creams containing all-trans-retinoic acid or all-trans-retinoyl beta-glucuronide on pig skin.

    PubMed

    Gunning, Desiree B; Barua, Arun B; Myers, Ronald K; Ueltschy, Amanda; Romans, David; Olson, James A

    2002-01-01

    The efficacy of all-trans-retinoic acid (tRA) and all-trans-retinoyl beta-glucuronide (RAG), a water-soluble metabolite of vitamin A, in the topical treatment of acne is comparable. However, whereas 3.3 mM tRA shows side effects, 3.3 mM RAG does not. To assess the relative toxic and histologic effects (dermal and epidermal changes) of long-term (24-week) daily applications of tRA and RAG on the skin, separate skin patches were measured and marked dorsally on the skin of six 21-day-old, castrated male pigs. Each skin patch area was treated daily with a cream formulation containing either 3.3 mM RAG, 16.5 mM RAG, 33 mM RAG, 3.3 mM tRA, 16.5 mM tRA or blank cream. To serve as controls, one patch received no treatment, one patch received blank cream only and for 5.3 weeks one 'washed' patch was given daily application of 33 mM RAG with routine cleansing using a mild soap typical of skin care. The amount of cream used per square centimeter remained the same during the course of the study. Biopsy tissue was collected at -1, 0, 2, 4, 8, 12 and 24 weeks from 7 test patches. The 'washed' patch was biopsied once at the 5.3-week mark. Topically applied RAG cream (3.3 mM) resulted in significantly lower histologic scores when compared with scores from tissue treated with an equimolar concentration of tRA. The highest concentration of RAG tested (33.3 mM) resulted in a response comparable to that observed in the lowest tRA (3.3 mM) treated patch area. Daily cleansing of the test area receiving 33.3 mM RAG completely eliminated any clinical signs or negative histologic changes. In conclusion, long-term topical tRA treatment in young pigs, as in humans, showed dose-dependent adverse effects on the skin, whereas RAG treatment had significantly lower histologic changes and less irritation and/or inflammation.

  4. Use of Adipose-Derived Stem Cells to Support Topical Skin Adhesive for Wound Closure: A Preliminary Report from Animal In Vivo Study

    PubMed Central

    Pietkun, Katarzyna; Jundziłł, Arkadiusz; Grzanka, Dariusz; Skopinska-Wisniewska, Joanna; Scibior, Kinga; Pokrywczyńska, Marta; Grzanka, Alina; Zegarski, Wojciech

    2016-01-01

    The aim of this study was to determine the local and systemic effects of adipose-derived stem cells (ADSCs) as a component of topical skin adhesive in an animal artificial wound closure model. In presented study the cosmetic effects, histological analysis, mechanical properties, and cell migration have been assessed to evaluate the usefulness of ADSCs as supporting factor for octyl blend cyanoacrylate adhesive. The total of 40 rats were used and divided into six groups. In the Study Group, ADSCs were administered by multipoint injection of the six surrounding intrawound areas with additional freely leaving procedure of the cells between the skin flaps just before applying adhesive to close the wound. Five control groups without using ADSCs, utilizing different types of standard wound closure, were created in order to check efficiency of experimental stem cell therapy. In our study, we proved that ADSCs could be used effectively also as a supportive tool in topical skin adhesive for wound closure. However we did not achieve any spectacular differences related to such aspects as better mechanical properties or special biological breakthroughs in wound healing properties. The use of stem cells, especially ADSCs for wound closure can provide an inspiring development in plastic and dermatologic surgery. PMID:27803921

  5. ERBB3 is required for tumor promotion in a mouse model of skin carcinogenesis.

    PubMed

    Dahlhoff, Maik; Schäfer, Matthias; Muzumdar, Sukalp; Rose, Christian; Schneider, Marlon R

    2015-11-01

    The epidermal growth factor receptor (EGFR) plays a key role in skin inflammation, wound healing, and carcinogenesis. Less is known about the functions of the structurally related receptor ERBB3 (HER3) in the skin. We assessed the requirement of ERBB3 for skin homeostasis, wound healing, and tumorigenesis by crossing mice carrying a conditional Erbb3 allele with animals expressing cre under the control of the keratin 5 promoter. Erbb3(del) mice, lacking ERBB3 specifically in keratinocytes, showed no obvious abnormalities. The EGFR was upregulated in Erbb3(del) skin, possibly compensating the loss of ERBB3. Nonetheless, healing of full-thickness excisional wounds was negatively affected by ERBB3 deficiency. To analyze the function of ERBB3 during tumorigenesis, we employed the established DMBA/TPA multi-stage chemical carcinogenesis protocol. Erbb3(del) mice remained free of papillomas for a longer time and had significantly reduced tumor burden compared to control littermates. Tumor cell proliferation was considerably reduced in Erbb3(del) mice, and loss of ERBB3 also impaired keratinocyte proliferation after a single application of TPA. In human skin tumor samples, upregulated ERBB3 expression was observed in squamous cell carcinoma, condyloma, and malignant melanoma. Thus, we conclude that ERBB3, while dispensable for the development and the homeostasis of the epidermis and its appendages, is required for proper wound healing and for the progression of skin tumors during multi-stage chemical carcinogenesis in mice. ERBB3 may also be important for human skin cancer progression. The latter effects most probably reflect a key role for ERBB3 in increasing cell proliferation after stimuli as wounding or carcinogenesis.

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

    PubMed

    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

    PubMed Central

    Lai, Dongmei; Wang, Fangyuan; Dong, Zhangli; Zhang, Qiuwan

    2014-01-01

    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. PMID:24879098

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

    PubMed

    Lai, Dongmei; Wang, Fangyuan; Dong, Zhangli; Zhang, Qiuwan

    2014-01-01

    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. PMID:24879098

  9. Confocal Raman spectroscopy: In vivo biochemical changes in the human skin by topical formulations under UV radiation.

    PubMed

    Tosato, M G; Orallo, D E; Ali, S M; Churio, M S; Martin, A A; Dicelio, L

    2015-12-01

    A new approach to the study of the effects on human skin of mycosporine-like amino acids (MAAs) and gadusol (Gad) incorporated in polymer gel is proposed in this work. The depth profile and photoprotector effects of Pluronic F127® gels containing each of the natural actives were evaluated by in vivo confocal Raman spectroscopy aiming at the analysis of the biochemical changes on human skin. Hierarchical cluster analysis (HCA) showed that the data corresponding to different depths of the skin, from surface to 4 μm, and from 6 to 16 μm, remained in the same cluster. In vivo Raman spectra, classified into five different layers of epidermis according to their similarities, indicated that the amount of Gad gel increased by about 26% in the outermost layer of the stratum corneum (SC) and that MAAs gel at 2 μm depth was 103.4% higher than in the outermost layer of the SC. Variations in the SC of urocanic acid at 1490-1515 cm(-1) and 1652 cm(-1) and histidine at 1318 cm(-1) were calculated, before and after UV exposure with or without gels. With the application of gels the vibrational modes that correspond to lipids in trans conformation (1063 and 1128 cm(-1)) increased with respect to normal skin, whereas gauche conformation (1085 cm(-1)) disappeared. Our studies suggest that gels protected the skin against the stress of the natural defense mechanism caused by high levels of UV exposure.

  10. Reduction of facial pigmentation of melasma by topical lignin peroxidase: A novel fast-acting skin-lightening agent

    PubMed Central

    ZHONG, SHAO-MIN; SUN, NAN; LIU, HUI-XIAN; NIU, YUE-QING; WU, YAN

    2015-01-01

    The aim of the present study was to evaluate the efficacy and safety of lignin peroxidase (LIP) as a skin-lightening agent in patients with melasma. A self-controlled clinical study was performed in 31 women who had melasma on both sides of the face. This study involved 8 weeks of a full-face product treatment. The skin color was measured at days 0, 7, 28 and 56 using a chromameter on the forehead and cheeks. Standardized digital photographic images of each side of the face of all subjects were captured by a complexion analysis system. Clinical scores of the pigmentation were determined by two dermatologists. After using the LIP whitening lotion for 7 days, the luminance (L*) values of the melasma and the normal skin were significantly increased from baseline. The L* values continued to increase at days 28 and 56. The melasma area severity index (MASI) score was statistically decreased after 28 days of treatment. No treatment-related adverse events were observed. LIP whitening lotion was able to eliminate the skin pigmentation after 7 days of treatment, and provides a completely innovative approach to rapid skin lightening. The LIP whitening lotion exhibited good compatibility and was well tolerated. PMID:25574195

  11. Vitamin A loaded solid lipid nanoparticles for topical use: occlusive properties and drug targeting to the upper skin.

    PubMed

    Jenning, V; Gysler, A; Schäfer-Korting, M; Gohla, S H

    2000-05-01

    To evaluate the potential use of solid lipid nanoparticles (SLN) in dermatology and cosmetics, glyceryl behenate SLN loaded with vitamin A (retinol and retinyl palmitate) and incorporated in a hydrogel and o/w-cream were tested with respect to their influence on drug penetration into porcine skin. Conventional formulations served for comparison. Excised full thickness skin was mounted in Franz diffusion cells and the formulations were applied for 6 and 24 h, respectively. Vitamin A concentrations in the skin tissue suggested a certain drug localizing effect. High retinol concentrations were found in the upper skin layers following SLN preparations, whereas the deeper regions showed only very low vitamin A levels. Because of a polymorphic transition of the lipid carrier with subsequent drug expulsion following the application to the skin, the drug localizing action appears to be limited for 6-24 h. Best results were obtained with retinol SLN incorporated in the oil-in-water (o/w) cream retarding drug expulsion. The penetration of the occlusion sensitive drug retinyl palmitate was even more influenced by SLN incorporation. Transepidermal water loss (TEWL) and the influence of drug free SLN on retinyl palmitate uptake exclude pronounced occlusive effects. Therefore enhanced retinyl palmitate uptake should derive from specific SLN effects and is not due to non-specific occlusive properties.

  12. Suppression of immediate and late anti-IgE-induced skin reactions by topically applied alcohol/onion extract.

    PubMed

    Dorsch, W; Ring, J

    1984-01-01

    In a double blind study, alcohol/onion extract (5% ethanol) was injected simultaneously with 20 IU and 200 IU rabbit anti-human-IgE intradermally in 12 adult volunteers (6 atopics, 6 non-atopics). Diameters of wheals and flares were measured 10 min after and compared with control sites challenged with 20 IU and 200 IU anti-IgE in a 5% ethanol solution. The skin sites were then treated epidermally with 45% alcohol/onion extract and 45% ethanol under occlusion. Diameters of late cutaneous reactions were measured hourly. Oedema formation was clinically estimated according to an arbitrary scale and skin thickness measured with a calliper. In the onion-treated skin sites the wheal areas were significantly reduced (20 IU: control: 108 +/- 53 mm2; onion 69 +/- 42 mm2, P less than 0.05; 200 IU anti-IgE: control: 152 +/- 25 mm2, onion: 138 +/- 26 mm2, P less than 0.02). The oedema formation during the late phase skin reaction was markedly depressed (P less than 0.005 at 2 h, P less than 0.01 at 4 and 6 h, P less than 0.02 at 8 h). The extent of late skin reactions was slightly, but not significantly reduced. Obviously, onions contain pharmacologically active substances with anti-inflammatory and/or allergic properties. PMID:6364880

  13. Topical application of alpha-tocopherol modulates the antioxidant network and diminishes ultraviolet-induced oxidative damage in murine skin.

    PubMed

    Lopez-Torres, M; Thiele, J J; Shindo, Y; Han, D; Packer, L

    1998-02-01

    The aim of this study was to investigate the effects of topical alpha-tocopherol application on epidermal and dermal antioxidants and its ability to prevent ultraviolet (UV)-induced oxidative damage. Hairless mice received topical applications of alpha-tocopherol 24 h before a single, acute UV irradiation (10 x minimal erythemal dose). The four major antioxidant enzymes (catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase), hydrophilic and lipophilic antioxidants, and lipid hydroperoxides, markers of oxidative damage, were assayed in both epidermis and dermis of hairless mice. Topical alpha-tocopherol treatment increased dermal superoxide dismutase activity by 30% (P < 0.01) and protected epidermal glutathione peroxidase and superoxide dismutase from depletion after UV irradiation. Total and reduced glutathione levels in the epidermis increased by 50% after the topical treatment (P < 0.05), as did dermal ascorbate levels (by 40%: P < 0.01). The topical treatment increased alpha-tocopherol levels both in the epidermis (62-fold) and the dermis (22-fold: P < 0.001 in each layer). Furthermore, alpha-tocopherol treatment significantly reduced the formation of epidermal lipid hydroperoxides after UV irradiation (P < 0.05). These results demonstrate that topical administration of alpha-tocopherol protects cutaneous tissues against oxidative damage induced by UV irradiation in vivo, and suggest that the underlying mechanism of this effect involves the up-regulation of a network of enzymatic and non-enzymatic antioxidants.

  14. FORMULATION DEVELOPMENT OF TOPICAL CREAM LOADED WITH ANANAS COMOSUS EXTRACT: IN VIVO EVALUATION FOR CHANGES IN SKIN BARRIER FUNCTION USING BIOPHYSICAL TECHNIQUES.

    PubMed

    Arshad, Atif I; Khan, Shoaib H M; Akhtar, Naveed

    2016-01-01

    The prime objective of current investigation was to develop a topical skin care cream (w/o) loaded with Ananas comosus extract versus placebo control, and evaluated non-invasively for changes in skin barrier function i.e., epidermal hydration levels and transepidermal water loss (TEWL), on healthy human volunteers. Active cream carrying 2% extract of Ananas comosus in the internal phase of w/o emulsion was prepared while placebo contained no extract. Stability assessment of both creams was performed at various storage conditions 8, 25, 40 degrees C, 40 degrees C + 75% RH (relative humidity) and 50 degrees C. Effects on epidermal hydration and TEWL were observed by applying active cream at one side and placebo on the other side of face by 11 healthy human volunteers during 12 weeks period using Corneometer MPA5 and Tewameter MPA5. Results indicated that both creams (active and placebo) remained stable at all storage conditions. All samples manifested non-Newtonian, shear thinning behavior with increasing shear rate, whereas statistical interpretation indicated that effects of active cream were superior than placebo, as it significantly (p = 0.05) improves the epidermal hydration levels up to 56.74% and reduces TEWL up to -73.19% at the end of study period compared to baseline value. The surface evaluation of living skin (SELS) parameters SEr, SEsc, SEsm, SEw were also assessed and indicated a significant (p = 0.05) reduction. Conclusively, creams loaded with Ananas comosus extract exhibit better physicochemical stability and represent a propitious improvement in skin barrier function, used as a functional moisturizing and anti-aging ingredient in topical skincare products. PMID:27180442

  15. FORMULATION DEVELOPMENT OF TOPICAL CREAM LOADED WITH ANANAS COMOSUS EXTRACT: IN VIVO EVALUATION FOR CHANGES IN SKIN BARRIER FUNCTION USING BIOPHYSICAL TECHNIQUES.

    PubMed

    Arshad, Atif I; Khan, Shoaib H M; Akhtar, Naveed

    2016-01-01

    The prime objective of current investigation was to develop a topical skin care cream (w/o) loaded with Ananas comosus extract versus placebo control, and evaluated non-invasively for changes in skin barrier function i.e., epidermal hydration levels and transepidermal water loss (TEWL), on healthy human volunteers. Active cream carrying 2% extract of Ananas comosus in the internal phase of w/o emulsion was prepared while placebo contained no extract. Stability assessment of both creams was performed at various storage conditions 8, 25, 40 degrees C, 40 degrees C + 75% RH (relative humidity) and 50 degrees C. Effects on epidermal hydration and TEWL were observed by applying active cream at one side and placebo on the other side of face by 11 healthy human volunteers during 12 weeks period using Corneometer MPA5 and Tewameter MPA5. Results indicated that both creams (active and placebo) remained stable at all storage conditions. All samples manifested non-Newtonian, shear thinning behavior with increasing shear rate, whereas statistical interpretation indicated that effects of active cream were superior than placebo, as it significantly (p = 0.05) improves the epidermal hydration levels up to 56.74% and reduces TEWL up to -73.19% at the end of study period compared to baseline value. The surface evaluation of living skin (SELS) parameters SEr, SEsc, SEsm, SEw were also assessed and indicated a significant (p = 0.05) reduction. Conclusively, creams loaded with Ananas comosus extract exhibit better physicochemical stability and represent a propitious improvement in skin barrier function, used as a functional moisturizing and anti-aging ingredient in topical skincare products.

  16. Protein Tyrosine Kinase 6 Regulates UVB-Induced Signaling and Tumorigenesis in Mouse Skin.

    PubMed

    Chastkofsky, Michael I; Bie, Wenjun; Ball-Kell, Susan M; He, Yu-Ying; Tyner, Angela L

    2015-10-01

    Protein tyrosine kinase 6 (PTK6, also called BRK) is an intracellular tyrosine kinase expressed in the epithelial linings of the gastrointestinal tract and the skin, where it is expressed in nondividing differentiated cells. We found that PTK6 expression increases in the epidermis following UVB treatment. To evaluate the roles of PTK6 in the skin following UVB-induced damage, we exposed back skin of Ptk6 +/+ and Ptk6 -/- SENCAR mice to incremental doses of UVB for 30 weeks. Wild-type mice were more sensitive to UVB and exhibited increased inflammation and greater activation of signal transducer and activator of transcription-3 (STAT3) than Ptk6-/- mice. Disruption of Ptk6 did not have an impact on proliferation, although PTK6 was expressed and activated in basal epithelial cells in wild-type mice following UVB treatment. However, wild-type mice exhibited shortened tumor latency and increased tumor load compared with Ptk6-/- mice, and STAT3 activation was increased in these tumors. PTK6 activation was detected in UVB-induced tumors, and this correlated with increased activating phosphorylation of focal adhesion kinase (FAK) and breast cancer anti-estrogen resistance 1 (BCAR1). Activation of PTK6 was also detected in human squamous cell carcinomas of the skin. Although PTK6 has roles in normal differentiation, it also contributes to UVB-induced injury and tumorigenesis in vivo. PMID:25938342

  17. Topical skin treatment with Fab fragments of an allergen-specific IgG1 monoclonal antibody suppresses allergen-induced atopic dermatitis-like skin lesions in mice.

    PubMed

    Sae-Wong, Chutha; Mizutani, Nobuaki; Kangsanant, Sureeporn; Yoshino, Shin

    2016-05-15

    Fab fragments (Fabs), which lack effector functions due to the absence of the Fc portion, maintain the ability to bind to specific allergens. In the present study, we examined whether Fabs of an allergen-specific IgG1 monoclonal antibody (mAb) were able to regulate allergen-induced atopic dermatitis-like skin lesions in mice. BALB/c mice passively sensitized with ovalbumin (OVA)-specific IgE mAb were repeatedly challenged with OVA applied to the skin after sodium dodecyl sulfate treatment. Fabs prepared by the digestion of anti-OVA IgG1 mAb (O1-10) with papain were applied to the skin 30min before the OVA challenges followed by measurement of clinical symptoms including erythema/hemorrhage, edema, scarring/dryness, and excoriation/erosion of the skin. Treatment with O1-10 Fabs, but not intact O1-10, showed inhibition of clinical symptoms (P<0.01) induced by the repeated OVA challenges in the sensitized mice; O1-10 Fabs suppressed histological changes such as epidermal hyperplasia (P<0.01) and the accumulation of mast cells (P<0.01) and neutrophils (P<0.01). Furthermore, treatment with O1-10 Fabs inhibited the increase in levels of IL-13 (P<0.01) and IL-17A production (P<0.05) in the lymph nodes of the sensitized mice. Additionally, the increased level of OVA in serum following the repeated OVA challenges in the sensitized mice was reduced by the treatment (P<0.05). These results suggest that topical application of pathogenic allergen-specific IgG1 mAb Fabs to the skin of mice is effective in suppressing allergen-induced atopic dermatitis-like skin lesions, suggesting that allergen-specific mAb Fabs could be used as a tool to regulate allergen-induced atopic dermatitis. PMID:26970183

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

    PubMed Central

    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

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

    PubMed

    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

  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.

    PubMed

    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. SLN as a topical delivery system for Artemisia arborescens essential oil: In vitro antiviral activity and skin permeation study

    PubMed Central

    Lai, Francesco; Sinico, Chiara; De Logu, Alessandro; Zaru, Marco; Müller, Rainer H; Fadda, Anna M

    2007-01-01

    The effect of SLN incorporation on transdermal delivery and in vitro antiherpetic activity of Artemisia arborescens essential oil was investigated. Two different SLN formulations were prepared using the hot – pressure homogenization technique, Compritol 888 ATO as lipid, and Poloxamer 188 and Miranol Ultra C32 as surfactants. Formulations were examined for their stability for two years by monitoring average size distribution and zeta potential values. The antiviral activity of free and SLN incorporated essential oil was tested in vitro against Herpes Simplex Virus-1 (HSV-1) by a quantitative tetrazolium-based colorimetric method (MTT), while the effects of essential oil incorporation into SLN on both the permeation through and the accumulation into the skin strata was investigated by using in vitro diffusion experiments through newborn pig skin and an almond oil Artemisia essential oil solution as a control. Results showed that both SLN formulations were able to entrap the essential oil in high yields and that the mean particle size increased only slightly after two years of storage, indicating a high physical stability. In vitro antiviral assays showed that SLN incorporation did not affect the essential oil antiherpetic activity. The in vitro skin permeation experiments demonstrated the capability of SLN of greatly improving the oil accumulation into the skin, while oil permeation occurred only when the oil was delivered from the control solution. PMID:18019840

  2. 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.

    PubMed

    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 < 0.005-0.001), catalase (51-92%, P < 0.001) and glutathione level (87-100%, P < 0.005). Treatment of EGCG or GTP also inhibited UVB-induced oxidative stress when measured in terms of lipid peroxidation (76-95%, P < 0.001), and protein oxidation (67-75%, 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 < 0.01-0.001), oxidative stress (33-71%, P < 0.01) and phosphorylation of ERK1/2, JNK and p38 proteins of MAPK family but the

  3. Differential gene expression profiling of mouse skin after sulfur mustard exposure: Extended time response and inhibitor effect

    SciTech Connect

    Gerecke, Donald R. Chen Minjun; Isukapalli, Sastry S.; Gordon, Marion K.; Chang, Y.-C.; Tong Weida; Androulakis, Ioannis P.; Georgopoulos, Panos G.

    2009-01-15

    Sulfur mustard (HD, SM), is a chemical warfare agent that within hours causes extensive blistering at the dermal-epidermal junction of skin. To better understand the progression of SM-induced blistering, gene expression profiling for mouse skin was performed after a single high dose of SM exposure. Punch biopsies of mouse ears were collected at both early and late time periods following SM exposure (previous studies only considered early time periods). The biopsies were examined for pathological disturbances and the samples further assayed for gene expression profiling using the Affymetrix microarray analysis system. Principal component analysis and hierarchical cluster analysis of the differently expressed genes, performed with ArrayTrack showed clear separation of the various groups. Pathway analysis employing the KEGG library and Ingenuity Pathway Analysis (IPA) indicated that cytokine-cytokine receptor interaction, cell adhesion molecules (CAMs), and hematopoietic cell lineage are common pathways affected at different time points. Gene ontology analysis identified the most significantly altered biological processes as the immune response, inflammatory response, and chemotaxis; these findings are consistent with other reported results for shorter time periods. Selected genes were chosen for RT-PCR verification and showed correlations in the general trends for the microarrays. Interleukin 1 beta was checked for biological analysis to confirm the presence of protein correlated to the corresponding microarray data. The impact of a matrix metalloproteinase inhibitor, MMP-2/MMP-9 inhibitor I, against SM exposure was assessed. These results can help in understanding the molecular mechanism of SM-induced blistering, as well as to test the efficacy of different inhibitors.

  4. Differential gene expression profiling of mouse skin after sulfur mustard exposure: Extended time response and inhibitor effect

    PubMed Central

    Gerecke, Donald R.; Chen, Minjun; Isukapalli, Sastry S.; Gordon, Marion K.; Chang, Yoke-Chen; Tong, Weida; Androulakis, Ioannis P.; Georgopoulos, Panos G.

    2011-01-01

    Sulfur mustard (HD, SM), is a chemical warfare agent that within hours causes extensive blistering at the dermal–epidermal junction of skin. To better understand the progression of SM-induced blistering, gene expression profiling for mouse skin was performed after a single high dose of SM exposure. Punch biopsies of mouse ears were collected at both early and late time periods following SM exposure (previous studies only considered early time periods). The biopsies were examined for pathological disturbances and the samples further assayed for gene expression profiling using the Affymetrix microarray analysis system. Principal component analysis and hierarchical cluster analysis of the differently expressed genes, performed with ArrayTrack showed clear separation of the various groups. Pathway analysis employing the KEGG library and Ingenuity Pathway Analysis (IPA) indicated that cytokine–cytokine receptor interaction, cell adhesion molecules (CAMs), and hematopoietic cell lineage are common pathways affected at different time points. Gene ontology analysis identified the most significantly altered biological processes as the immune response, inflammatory response, and chemotaxis; these findings are consistent with other reported results for shorter time periods. Selected genes were chosen for RT-PCR verification and showed correlations in the general trends for the microarrays. Interleukin 1 beta was checked for biological analysis to confirm the presence of protein correlated to the corresponding microarray data. The impact of a matrix metalloproteinase inhibitor, MMP-2/MMP-9 inhibitor I, against SM exposure was assessed. These results can help in understanding the molecular mechanism of SM-induced blistering, as well as to test the efficacy of different inhibitors. PMID:18955075

  5. Alterations in the expression of uvomorulin and Na+,K(+)-adenosine triphosphatase during mouse skin tumor progression.

    PubMed Central

    Ruggeri, B.; Caamano, J.; Slaga, T. J.; Conti, C. J.; Nelson, W. J.; Klein-Szanto, A. J.

    1992-01-01

    Uvomorulin (E-cadherin), a cell adhesion molecule, and Na+,K(+)-adenosine triphosphatase (ATPase), a marker protein of the basal-lateral cell membrane domains of polarized epithelial cells, were investigated in a group of mouse skin tumors induced by a two-stage chemical carcinogenesis protocol and in cell lines derived from mouse skin papillomas and squamous cell carcinomas (SCC). Although these two markers were present in benign tumors and in nontumorigenic cell lines, the Na+,K(+)-ATPase showed an altered pattern of distribution that included the presence of enzyme not only in the basolateral domain but also on the apical domain of the cell membrane of basal and spinous cells in well-differentiated squamous cell carcinomas (SCC). In higher grade SCC, a loss of Na+,K(+)-ATPase immunoreactivity was simultaneously detected with a marginal or absent expression of uvomorulin. The more differentiated SCC and papillomas expressed less uvomorulin immunoreactivity than normal epidermal cells. Both markers were seen in tumor cell lines that produced well-differentiated SCC after subcutaneous inoculation into nude mice. Neither Na+,K(+)-ATPase nor uvomorulin could be detected in cell lines that produced high grade, poorly differentiated SCC. Northern blots confirmed the absence of uvomorulin mRNA in these highly malignant cell lines. These data indicate that progression from premalignant papilloma to low-grade SCC and subsequently to high-grade SCC is accompanied by loss of epithelial cell polarity as detected by changes in Na+,K(+)-ATPase and by decreased or absent expression of uvomorulin in tumors and cell lines characterized by an advanced malignant phenotype. Images Figure 1 Figure 2 Figure 3 PMID:1316085

  6. A novel ex vivo skin model for the assessment of the potential transcutaneous anti-inflammatory effect of topically applied Harpagophytum procumbens extract.

    PubMed

    Ouitas, Nassima Abdelouahab; Heard, Charles M

    2009-07-01

    Using ex vivo skin as a model, this work tested the hypothesis that the major pharmacologically active components of topically applied Harpagophytum procumbens (H. procumbens) can elicit anti-inflammatory responses in deeper tissues post-transcutaneous delivery. Using Franz-type diffusion cells, ethanol extract of powdered H. procumbens tuber was dosed onto freshly excised porcine skin. After 24 h the receptor phase was recovered, analysed for the major glycosides of DC, then used directly to dose further freshly excised skin membranes. After 6h the skin was recovered and probed for the expression of the three major enzymes involved in the inflammatory factors: cyclooxygenase (COX-2) and its product prostaglandin E2 (PGE-2), lipoxygenase (5-LOX), and inducible nitric oxide (iNOS), using immunocytochemistry and Western blotting analyses. It was found that the receptor phase at 24 h contained (0.8, 25, 1.8, 3 x 10(-3)) micromol mL(-1) of harpagoside, harpagide, verbascoside, 8-O-p-coumaroyl-harpagide, respectively. When applied to skin, this solution effectively inhibited the expression of COX-2 and its product PGE-2. However, it did not have a significant effect on either 5-LOX or iNOS compared to control samples (PBS only). These data support the hypothesis that the transcutaneous delivery of H. procumbens can treat inflammation in deeper tissues such as in arthritis. Moreover, a novel ex vivo model has been described for assessing the potential anti-inflammatory activity of permeants delivered to deeper subcutaneous regions. PMID:19383533

  7. Topical treatment with the vitamin D analogue calcipotriol enhances the upregulation of the antimicrobial protein hCAP18/LL-37 during wounding in human skin in vivo.

    PubMed

    Heilborn, Johan D; Weber, Günther; Grönberg, Alvar; Dieterich, Christine; Ståhle, Mona

    2010-04-01

    Cathelicidin antimicrobial protein, hCAP18, is the sole cathelin protein in human. Its C-terminal peptide, which is released enzymatically from the holoprotein, has broad antimicrobial activity but also has effects on eukaryotic cells. hCAP18 is present in leukocytes and is produced at epithelial interfaces as part of the innate immune system. In normal intact skin, there is low constitutive expression of hCAP18, which is rapidly upregulated upon injury. Accumulating evidence indicates that hCAP18/LL-37 may serve a key role in protecting the integrity of the epithelium and also actively promote re-epithelialization and tissue repair. Molecular mechanisms responsible for controlling hCAP18 gene expression in vivo are only partly understood. Vitamin D(3) and its analogue calcipotriol were recently found to directly induce transcription of the hCAP18 gene via functional vitamin D responsive elements in the hCAP18 gene promoter. Skin is the major source for vitamin D(3) in human, where its production is dependent on ultraviolet B (UVB) radiation. We have shown that exposure to UVB, sufficient to produce vitamin D(3), upregulates hCAP18 in human skin in vivo. In the present study, we demonstrate that the upregulation of hCAP18/LL-37 following acute skin injury is further enhanced, at both hCAP18 mRNA and protein levels, after topical treatment with the vitamin D(3) analogue calcipotriol. In chronic ulcers, calcipotriol treatment upregulated hCAP18 mRNA, whereas no consistent upregulation of hCAP18 protein was detected. Our results further support the role of vitamin D(3) as a key physiologic regulator of hCAP18/LL-37 in human skin.

  8. Staphylococcus δ-toxin promotes mouse allergic skin disease by inducing mast cell degranulation

    PubMed Central

    Nakamura, Yuumi; Oscherwitz, Jon; Cease, Kemp B.; Chan, Susana M.; Muñoz-Planillo, Raul; Hasegawa, Mizuho; Villaruz, Amer E.; Cheung, Gordon Y. C.; McGavin, Martin J.; Travers, Jeffrey B.; Otto, Michael; Inohara, Naohiro; Núñez, Gabriel

    2013-01-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects 15 to 30% of children and ~5% of adults in industrialized countries1. Although the pathogenesis of AD is not fully understood, the disease is mediated by an abnormal immunoglobulin E (IgE) immune response in the setting of skin barrier dysfunction2. Mast cells (MCs) contribute to IgE-mediated allergic disorders including AD3. Upon activation, MCs release their membrane-bound cytosolic granules leading to the release of multiple molecules that are important in the pathogenesis of AD and host defense4. More than 90% of AD patients are colonized with Staphylococcus aureus in the lesional skin whereas most healthy individuals do not harbor the pathogen5. Several Staphylococcal exotoxins (SEs) can act as superantigens and/or antigens in models of AD6. However, the role of these SEs in disease pathogenesis remains unclear. Here, we report that culture supernatants of S. aureus contain potent MC degranulation activity. Biochemical analysis identified δ-toxin as the MC degranulation-inducing factor produced by S. aureus. MC degranulation induced by δ-toxin depended on phosphoinositide 3-kinase (PI3K) and calcium (Ca2+) influx, but unlike that mediated by IgE crosslinking, it did not require the spleen tyrosine kinase (Syk). In addition, IgE enhanced δ-toxin-induced MC degranulation in the absence of antigen. Furthermore, S. aureus isolates recovered from AD patients produced high levels of δ-toxin. Importantly, skin colonization with S. aureus, but not a mutant deficient in δ-toxin, promoted IgE and IL-4 production, as well as inflammatory skin disease. Furthermore, enhancement of IgE production and dermatitis by δ-toxin was abrogated in KitW-sh/W-sh MC-deficient mice and restored by MC reconstitution. These studies identify δ-toxin as a potent inducer of MC degranulation and suggest a mechanistic link between S. aureus colonization and allergic skin disease. PMID:24172897

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Minjuan, Wu; Jun, Xiong; Shiyun, Shao; Sha, Xu; Haitao, Ni; Yue, Wang; Kaihong, Ji

    2016-01-01

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

  12. Dynamic change of histone H2AX phosphorylation independent of ATM and DNA-PK in mouse skin in situ

    SciTech Connect

    Koike, Manabu Mashino, Minako; Sugasawa, Jun; Koike, Aki

    2007-11-30

    Histone H2AX undergoes phosphorylation on Ser 139 ({gamma}-H2AX) rapidly in response to DNA double-strand breaks induced by exogenous stimuli, such as ionizing radiation. However, the endogenous phosphorylation pattern and modifier of H2AX remain unclear. Here we show that H2AX is regulated physically at the level of phosphorylation at Ser139 during a hair cycle in the mouse skin. In anagen hair follicles, {gamma}-H2AX-positive cells were observed in the outer root sheath (ORS) and hair bulb in a cycling inferior region but not in a permanent superficial region. In telogen hair follicles, {gamma}-H2AX-positive cells were only detected around the germ cell cap. In contrast, following X-irradiation, {gamma}-H2AX was observed in various cell types including the ORS cells in the permanent superficial region. Furthermore, {gamma}-H2AX-positive cells were detected in the skin of mice lacking either ATM or DNA-PK, suggesting that these kinases are not essential for phosphorylation in vivo.

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

    PubMed

    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.

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  16. Unexpected reduction of skin tumorigenesis on expression of cyclin-dependent kinase 6 in mouse epidermis.

    PubMed

    Wang, Xian; Sistrunk, Christopher; Rodriguez-Puebla, Marcelo L

    2011-01-01

    Cyclin-dependent kinases (CDKs) 4 and 6 are important regulators of the G(1) phase of the cell cycle, share 71% amino acid identity, and are expressed ubiquitously. As a result, it was assumed that each of these kinases plays a redundant role regulating normal and neoplastic proliferation. In previous reports, we have described the effects of CDK4 expression in transgenic mice, including the development of epidermal hyperplasia and increased malignant progression to squamous cell carcinoma. To study the role of CDK6 in epithelial growth and tumorigenesis, we generated transgenic mice carrying the CDK6 gene under the keratin 5 promoter (K5CDK6). Similar to K5CDK4 mice, epidermal proliferation increased substantially in K5CDK6 mice; however, no hyperplasia was observed. CDK6 overexpression also triggered keratinocyte apoptosis in interfollicular and follicular epidermis as a compensatory mechanism to override aberrant proliferation. Unexpectedly, CDK6 overexpression results in decreased skin tumor development compared with wild-type siblings. The inhibition in skin tumorigenesis was similar to that previously reported in K5-cyclin D3 mice. Furthermore, biochemical analysis of the K5CDK6 epidermis showed preferential complex formation between CDK6 and cyclin D3, suggesting that this particular complex plays an important role in tumor restraint. These studies provide in vivo evidence that CDK4 and CDK6 play a similar role as a mediator of keratinocyte proliferation but differ in apoptosis activation and skin tumor development.

  17. Unexpected reduction of skin tumorigenesis on expression of cyclin-dependent kinase 6 in mouse epidermis.

    PubMed

    Wang, Xian; Sistrunk, Christopher; Rodriguez-Puebla, Marcelo L

    2011-01-01

    Cyclin-dependent kinases (CDKs) 4 and 6 are important regulators of the G(1) phase of the cell cycle, share 71% amino acid identity, and are expressed ubiquitously. As a result, it was assumed that each of these kinases plays a redundant role regulating normal and neoplastic proliferation. In previous reports, we have described the effects of CDK4 expression in transgenic mice, including the development of epidermal hyperplasia and increased malignant progression to squamous cell carcinoma. To study the role of CDK6 in epithelial growth and tumorigenesis, we generated transgenic mice carrying the CDK6 gene under the keratin 5 promoter (K5CDK6). Similar to K5CDK4 mice, epidermal proliferation increased substantially in K5CDK6 mice; however, no hyperplasia was observed. CDK6 overexpression also triggered keratinocyte apoptosis in interfollicular and follicular epidermis as a compensatory mechanism to override aberrant proliferation. Unexpectedly, CDK6 overexpression results in decreased skin tumor development compared with wild-type siblings. The inhibition in skin tumorigenesis was similar to that previously reported in K5-cyclin D3 mice. Furthermore, biochemical analysis of the K5CDK6 epidermis showed preferential complex formation between CDK6 and cyclin D3, suggesting that this particular complex plays an important role in tumor restraint. These studies provide in vivo evidence that CDK4 and CDK6 play a similar role as a mediator of keratinocyte proliferation but differ in apoptosis activation and skin tumor development. PMID:21224071

  18. Unexpected Reduction of Skin Tumorigenesis on Expression of Cyclin-Dependent Kinase 6 in Mouse Epidermis

    PubMed Central

    Wang, Xian; Sistrunk, Christopher; Rodriguez-Puebla, Marcelo L.

    2011-01-01

    Cyclin-dependent kinases (CDKs) 4 and 6 are important regulators of the G1 phase of the cell cycle, share 71% amino acid identity, and are expressed ubiquitously. As a result, it was assumed that each of these kinases plays a redundant role regulating normal and neoplastic proliferation. In previous reports, we have described the effects of CDK4 expression in transgenic mice, including the development of epidermal hyperplasia and increased malignant progression to squamous cell carcinoma. To study the role of CDK6 in epithelial growth and tumorigenesis, we generated transgenic mice carrying the CDK6 gene under the keratin 5 promoter (K5CDK6). Similar to K5CDK4 mice, epidermal proliferation increased substantially in K5CDK6 mice; however, no hyperplasia was observed. CDK6 overexpression also triggered keratinocyte apoptosis in interfollicular and follicular epidermis as a compensatory mechanism to override aberrant proliferation. Unexpectedly, CDK6 overexpression results in decreased skin tumor development compared with wild-type siblings. The inhibition in skin tumorigenesis was similar to that previously reported in K5-cyclin D3 mice. Furthermore, biochemical analysis of the K5CDK6 epidermis showed preferential complex formation between CDK6 and cyclin D3, suggesting that this particular complex plays an important role in tumor restraint. These studies provide in vivo evidence that CDK4 and CDK6 play a similar role as a mediator of keratinocyte proliferation but differ in apoptosis activation and skin tumor development. PMID:21224071

  19. Protective effect of topical application of α-tocopherol and/or N-acetyl cysteine on argemone oil/alkaloid-induced skin tumorigenesis in mice.

    PubMed

    Pal, Anu; Alam, Shamshad; Singhal, Jaya; Kumar, Rahul; Ansari, Kausar M; Das, Mukul

    2013-01-01

    Since bioantioxidants in plasma of Epidemic Dropsy patients [a condition caused by consumption of adulterated mustard oil with argemone oil (AO)] were found to be significantly decreased, the beneficial effect of N-acetyl cysteine (NAC) and α-tocopherol (TOCO) against AO- or sanguinarine (SANG)-induced tumorigenicity was undertaken in mice. Topical application of TOCO and NAC either alone or in combination showed significant protection against AO/TPA- and SANG/TPA-induced skin tumorigenicity. Histopathological findings suggest that papillomatous growth in AO/TPA- and SANG/TPA-treated animals were substantially protected following topical application of TOCO or NAC. Further, treatment of TOCO and NAC either alone or in combination to AO/TPA- or SANG/TPA-induced mice significantly decreased lipid peroxidation, along with significant revival in glutathione (GSH) content and activities of tyrosinase, histidase, catalase, SOD, GSH peroxidase, and GSH reductase in skin. In vitro studies showed that TOCO and/or NAC significantly decreased the AO and SANG induced cell proliferation and activation of ERK, p38, JNK MAPKs and NF-κB signaling in HaCaT cells. In summary, TOCO and NAC may be useful in preventing the tumorigenic response of AO and SANG probably by acting as scavenger of free radicals and inhibiting MAPKs and NF-κB signaling.

  20. Efficient Cellular Entry of (r-x-r)-Type Carbamate-Plasmid DNA Complexes and Its Implication for Noninvasive Topical DNA Delivery to Skin.

    PubMed

    Vij, Manika; Natarajan, Poornemaa; Yadav, Amit K; Patil, Kiran M; Pandey, Tanuja; Gupta, Nidhi; Santhiya, Deenan; Kumar, Vaijayanti A; Fernandes, Moneesha; Ganguli, Munia

    2016-06-01

    Arginine-rich cell penetrating peptides are powerful tools for in vitro as well as in vivo delivery of a wide plethora of biomolecules. However, presence of consecutive arginine residues leads to enhanced amenability for proteolytic degradation as well as steric hindrances for membrane interactions which compromise its bioavailability. In order to overcome these limitations we previously reported a safe and stable octaarginine based oligomer, i.e., (r-x-r)4-carbamate, where the backbone amide linkages were replaced by carbamate linkages and 6-aminohexanoic acid based spacer moieties were incorporated for better flexibility, hydrophobicity, optimal spacing of guanidinium groups, and protection against proteolytic cleavage; resulting in improved transfection efficiency over its amide counterpart. In the present work we have investigated the mechanism behind this enhanced transfection efficiency and, based on our observations, demonstrate how the synergistic effect of rationalized oligomer designing, complex characteristics, and cell type contributes to overall effective intracellular delivery. Our results indicate that the (r-x-r)4-carbamate-plasmid DNA complexes primarily utilize lipid raft dependent pathway of cellular entry more than other pathways, and this possibly facilitates their increased entry in the lipid raft rich milieu of skin cells. We also emphasize the utility of oligomer (r-x-r)4-carbamate as an efficient carrier for topical delivery of nucleic acids in skin tissue. This carrier can be utilized for safe, efficient, and noninvasive delivery of therapeutically relevant macromolecular hydrophilic cargo like nucleic acids to skin. PMID:27175623

  1. Domoprednate (Stermonid), a topical D-homocorticosteroid, skin atrophy and telangiectasia. A double-blind, randomized comparison with hydrocortisone butyrate, betamethasone valerate, clobetasole propionate and placebo.

    PubMed

    Serup, J; Holm, P

    1985-01-01

    Five corticosteroid ointments and placebo were compared in 17 volunteers with regard to their influence on normal skin under occlusive conditions. Each volunteer had six simultaneous applications on the forearms and six on the back. The trial was double-blind and lasted 4 weeks. The ointments were placed in randomized order. The treatments were 0.1 and 0.03% domoprednate, 0.1% hydrocortisone butyrate, 0.1% betamethasone valerate, 0.05% clobetasole propionate and placebo. Skin thickness was measured on days 0, 7, 14, 21 and 28, transepidermal water loss on days 0, 14 and 28, while blood flow and telangiectasias were evaluated only on day 28 at termination of the trial. The skin thickness became significantly reduced on all corticosteroids, but not on placebo; 0.03% domoprednate, however, tended to have an intermediate position between placebo and the other ointments. The transepidermal water loss did not change. Rating of telangiectasia under stereomicroscope showed a significantly lower score after 0.03% domoprednate and placebo as compared to the other ointments. Assessment of telangiectasia by laser-Doppler flowmetry showed a similar tendency. It is concluded that 0.1% domoprednate is comparable to other topical corticosteroids with respect to atrophogeneity and formation of telangiectasia, but the 0.03% concentration seems to result in fewer side effects.

  2. Efficient Cellular Entry of (r-x-r)-Type Carbamate-Plasmid DNA Complexes and Its Implication for Noninvasive Topical DNA Delivery to Skin.

    PubMed

    Vij, Manika; Natarajan, Poornemaa; Yadav, Amit K; Patil, Kiran M; Pandey, Tanuja; Gupta, Nidhi; Santhiya, Deenan; Kumar, Vaijayanti A; Fernandes, Moneesha; Ganguli, Munia

    2016-06-01

    Arginine-rich cell penetrating peptides are powerful tools for in vitro as well as in vivo delivery of a wide plethora of biomolecules. However, presence of consecutive arginine residues leads to enhanced amenability for proteolytic degradation as well as steric hindrances for membrane interactions which compromise its bioavailability. In order to overcome these limitations we previously reported a safe and stable octaarginine based oligomer, i.e., (r-x-r)4-carbamate, where the backbone amide linkages were replaced by carbamate linkages and 6-aminohexanoic acid based spacer moieties were incorporated for better flexibility, hydrophobicity, optimal spacing of guanidinium groups, and protection against proteolytic cleavage; resulting in improved transfection efficiency over its amide counterpart. In the present work we have investigated the mechanism behind this enhanced transfection efficiency and, based on our observations, demonstrate how the synergistic effect of rationalized oligomer designing, complex characteristics, and cell type contributes to overall effective intracellular delivery. Our results indicate that the (r-x-r)4-carbamate-plasmid DNA complexes primarily utilize lipid raft dependent pathway of cellular entry more than other pathways, and this possibly facilitates their increased entry in the lipid raft rich milieu of skin cells. We also emphasize the utility of oligomer (r-x-r)4-carbamate as an efficient carrier for topical delivery of nucleic acids in skin tissue. This carrier can be utilized for safe, efficient, and noninvasive delivery of therapeutically relevant macromolecular hydrophilic cargo like nucleic acids to skin.

  3. Effects of Food-Derived Collagen Peptides on the Expression of Keratin and Keratin-Associated Protein Genes in the Mouse Skin.

    PubMed

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

    2015-01-01

    Oral ingestion of collagen peptides (CP) has long been suggested to exert beneficial effects on the skin, but the molecular events induced by CP on the skin remain unclear. Here, we investigated the effects of oral CP administration on gene expression in hairless mouse skin and of prolyl-hydroxyproline (Pro-Hyp), a collagen-derived dipeptide, on gene expression in a coculture of mouse skin keratinocytes and fibroblasts. Using microarray analysis, we found that oral administration of CP to hairless mice for 6 weeks induced increased expression of Krtap and Krt genes in the skin. Annotation analysis using DAVID revealed that a group of the up-regulated genes, Gprc5d, Sprr2a1, Krt27 and Krtap16-7, is associated with the development of the epidermis and the hair cycle. In addition, the presence of Pro-Hyp (200 μM) induced an increase in the expression of Krtap16-7, Krtap15, Krtap14 and Krtap8-2 in keratinocytes in coculture, partially resembling the in vivo result. The Pro-Hyp-induced up-regulation of these genes was not observed when keratinocytes were cultured without fibroblasts, suggesting that the presence of fibroblasts is essential for the effects of Pro-Hyp. Our study presents new insights into the effects of CP on the skin, which might link to the hair cycle. PMID:25721900

  4. Suppression of tumor promoter-induced oxidative stress and inflammatory responses in mouse skin by a superoxide generation inhibitor 1'-acetoxychavicol acetate.

    PubMed

    Nakamura, Y; Murakami, A; Ohto, Y; Torikai, K; Tanaka, T; Ohigashi, H

    1998-11-01

    Double applications of phorbol esters trigger excessive reactive oxygen species (ROS) production in mouse skin. Previously reported data suggest that the two applications induce distinguishable biochemical events, namely, priming and activation. The former is characterized as a recruitment of inflammatory cells, such as neutrophils, by chemotactic factors to inflammatory regions and edema formation. The latter is responsible for ROS generation. Thus, inhibitory effects of 1'-acetoxychavicol acetate (ACA), previously reported to be a superoxide generation inhibitor in vitro, on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced oxidative stress and inflammatory responses in mouse skin model were examined using a double application of ACA. We demonstrated that two pretreatments and pretreatment with ACA (810 nmol) in the activation phase suppressed double TPA application-induced H2O2 formation in mouse skin. ACA exhibited no inhibitory effects on edema formation and the enhancement of myeloperoxidase activity during the first TPA treatment, whereas the anti-inflammatory agent genistein administered at the same dose inhibited both biomarkers. No inhibitory potential of ACA for TPA-induced H2O2 formation in the priming phase was confirmed. On the other hand, in the in vitro study, ACA inhibited ROS generation in differentiated HL-60 cells more strongly than did 1'-hydroxychavicol, which showed no inhibition by pretreatment in the activation phase. In addition, allopurinol did not inhibit double TPA application-induced H2O2 formation in mouse skin. These findings suggest that the NADPH oxidase system of neutrophils rather than the epithelial xanthine oxidase system is dominant for the O2--generating potential in double TPA-treated mouse skin. ACA significantly inhibited mouse epidermis thiobarbituric acid-reacting substance formation, known as an overall oxidative damage biomarker. Moreover, histological studies demonstrated that ACA inhibited double TPA treatment

  5. Study of protein modifications induced by phorbol ester tumor promoters in mouse skin

    SciTech Connect

    Nelson, K.G.

    1981-08-01

    The purpose of this study was to determine if the phorbol ester tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA) induced any specific changes in mouse epidermal proteins using the high resolution technique of two-dimensional electrophoresis. To accomplish this goal of determining the specificity and possibly the stage in promotion with which these protein changes were associated, epidermal proteins were analyzed (1) after treatment of adult mouse epidermis with several weakly promoting hyperplasiogenic agents, (2) following treatment with TPA in combination with various inhibitors of tumor promotion, (3) in basal kerotinocytes isolated from adult epidermis following treatment with TPA or several weakly promoting agents, and (4) during an initiation-promotion experiment. Evidence was found which indicated that the potent tumor promoter TPA as well as the weakly promoting hyperplasiogenic agents, mezerein, ethylphenylpropiolate (EPP), and mechanical abrasion, induced similar modifications of epidermal proteins, particularly among the keratins. These keratin modifications progressed with time following treatment resulting in a keratin pattern which resembled that of newborn epidermis.

  6. Isolation and evaluation of anticancer efficacy of stigmasterol in a mouse model of DMBA-induced skin carcinoma

    PubMed Central

    Ali, Huma; Dixit, Savita; Ali, Daoud; Alqahtani, Saeed M; Alkahtani, Saad; Alarifi, Saud

    2015-01-01

    Stigmasterol (99.9% pure) was isolated from Azadirachta indica and its chemopreventive effect on 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer was investigated in Swiss albino mice. Skin tumors were induced by topical application of DMBA and promoted by croton oil. To assess the chemopreventive potential of stigmasterol, it was orally administered at a concentration of 200 mg/kg and 400 mg/kg three times weekly for 16 weeks. Reduction in tumor size and cumulative number of papillomas were seen as a result of treatment with stigmasterol. The average latency period was significantly increased as compared with the carcinogen-treated control. Stigmasterol induced a significant decrease in the activity of serum enzymes, such as aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin as compared with the control. Stigmasterol significantly increased glutathione, superoxide dismutase, and catalase as compared with the control. Elevated levels of lipid peroxide and DNA damage in the control group were significantly inhibited by administration of stigmasterol. From the present study, it can be inferred that stigmasterol has chemopreventive activity in an experimental model of cancer. This chemopreventive activity may be linked to the oxidative stress of stigmasterol. The antigenotoxic properties of stigmasterol are also likely to contribute to its chemopreventive action. PMID:26060396

  7. Improvement of photoaged facial skin in middle-aged Japanese females by topical retinol (vitamin A alcohol): a vehicle-controlled, double-blind study.

    PubMed

    Kikuchi, Katsuko; Suetake, Takaki; Kumasaka, Naka; Tagami, Hachiro

    2009-01-01

    Topical tretinoin formulation is still unavailable in Japan. Because topical retinol, which is less potent but may cause less irritation, is available here, we have performed a randomized, blinded, vehicle-controlled study on the face using a once-nightly regimen for the treatment of mild photoaging in middle-aged Japanese females. First, a 26-week study was conducted in 57 subjects with a 0.075% retinol cream and its vehicle on each half side of the face. Three of the 57 subjects withdrew from the study due to irritation, although this rate was much smaller than that noted in our previous study with topical tretinoin. After 26 weeks, the rates of photoaging improvement were significantly higher on the retinol side: 27 out of 54 (50%) versus 13 (24%) for the fine wrinkling and 15 out of 54 (28%) versus 1 (2%) for deep wrinkling. A similar trial with a 0.04% retinol cream for 13 weeks revealed less prominent improvements in fine wrinkling but minimal irritation. From these data, we think that retinol creams, especially 0.04% cream, are suitable for daily use in the general population because of the low irritancy, even for those with sensitive skin.

  8. In Vivo Imaging Reveals a Pioneer Wave of Monocyte Recruitment into Mouse Skin Wounds

    PubMed Central

    Rodero, Mathieu P.; Licata, Fabrice; Poupel, Lucie; Hamon, Pauline; Khosrotehrani, Kiarash; Combadiere, Christophe; Boissonnas, Alexandre

    2014-01-01

    The cells of the mononuclear phagocyte system are essential for the correct healing of adult skin wounds, but their specific functions remain ill-defined. The absence of granulation tissue immediately after skin injury makes it challenging to study the role of mononuclear phagocytes at the initiation of this inflammatory stage. To study their recruitment and migratory behavior within the wound bed, we developed a new model for real-time in vivo imaging of the wound, using transgenic mice that express green and cyan fluorescent proteins and specifically target monocytes. Within hours after the scalp injury, monocytes invaded the wound bed. The complete abrogation of this infiltration in monocyte-deficient CCR2−/− mice argues for the involvement of classical monocytes in this process. Monocyte infiltration unexpectedly occurred as early as neutrophil recruitment did and resulted from active release from the bloodstream toward the matrix through microhemorrhages rather than transendothelial migration. Monocytes randomly scouted around the wound bed, progressively slowed down, and stopped. Our approach identified and characterized a rapid and earlier than expected wave of monocyte infiltration and provides a novel framework for investigating the role of these cells during early stages of wound healing. PMID:25272047

  9. Simultaneous absorption of vitamins C and E from