UV-induced skin damage

International Nuclear Information System (INIS)

Ichihashi, M.; Ueda, M.; Budiyanto, A.; Bito, T.; Oka, M.; Fukunaga, M.; Tsuru, K.; Horikawa, T.

2003-01-01

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

Effect of chemical peeling on the skin in relation to UV irradiation.

Science.gov (United States)

Funasaka, Yoko; Abdel-Daim, Mohamed; Kawana, Seiji; Nishigori, Chikako

2012-07-01

Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photoaged skin. However, it needs to be clarified whether the repetitive procedure of chemical peeling on photodamaged skin is safe and whether the different chemicals used for peeling results in similar outcomes or not. In this article, we reviewed the effect of peeling or peeling agents on the skin in relation to ultraviolet (UV) radiation. The pretreatment of peeling agents usually enhance UV sensitivity by inducing increased sunburn cell formation, lowering minimum erythematous dose and increasing cyclobutane pyrimidine dimers. However, this sensitivity is reversible and recovers to normal after 1-week discontinuation. Using animals, the chronic effect of peeling and peeling agents was shown to prevent photocarcinogenesis. There is also an in vitro study using culture cells to know the detailed mechanisms of peeling agents, especially on cell proliferation and apoptotic changes via activating signalling cascades and oxidative stress. It is important to understand the effect of peeling agents on photoaged skin and to know how to deal with UV irradiation during the application of peeling agents and treatment of chemical peeling in daily life. © 2012 John Wiley & Sons A/S.

Innate sensing of microbial products promotes wound-induced skin cancer

Science.gov (United States)

Hoste, Esther; Arwert, Esther N.; Lal, Rohit; South, Andrew P.; Salas-Alanis, Julio C.; Murrell, Dedee F.; Donati, Giacomo; Watt, Fiona M.

2015-01-01

The association between tissue damage, chronic inflammation and cancer is well known. However, the underlying mechanisms are unclear. Here we characterize a mouse model in which constitutive epidermal extracellular-signal-regulated kinase-MAP-kinase signalling results in epidermal inflammation, and skin wounding induces tumours. We show that tumour incidence correlates with wound size and inflammatory infiltrate. Ablation of tumour necrosis factor receptor (TNFR)-1/-2, Myeloid Differentiation primary response gene 88 or Toll-like receptor (TLR)-5, the bacterial flagellin receptor, but not other innate immune sensors, in radiosensitive leukocytes protects against tumour formation. Antibiotic treatment inhibits, whereas injection of flagellin induces, tumours in a TLR-5-dependent manner. TLR-5 is also involved in chemical-induced skin carcinogenesis in wild-type mice. Leukocytic TLR-5 signalling mediates upregulation of the alarmin HMGB1 (High Mobility Group Box 1) in wound-induced papillomas. HMGB1 is elevated in tumours of patients with Recessive Dystrophic Epidermolysis Bullosa, a disease characterized by chronic skin damage. We conclude that in our experimental model the combination of bacteria, chronic inflammation and wounding cooperate to trigger skin cancer. PMID:25575023

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

Science.gov (United States)

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

A synthetic peptide blocking TRPV1 activation inhibits UV-induced skin responses.

Science.gov (United States)

Kang, So Min; Han, Sangbum; Oh, Jang-Hee; Lee, Young Mee; Park, Chi-Hyun; Shin, Chang-Yup; Lee, Dong Hun; Chung, Jin Ho

2017-10-01

Transient receptor potential type 1 (TRPV1) can be activated by ultraviolet (UV) irradiation, and mediates UV-induced matrix metalloproteinase (MMP)-1 and proinflammatory cytokines in keratinocytes. Various chemicals and compounds targeting TRPV1 activation have been developed, but are not in clinical use mostly due to their safety issues. We aimed to develop a novel TRPV1-targeting peptide to inhibit UV-induced responses in human skin. We designed and generated a novel TRPV1 inhibitory peptide (TIP) which mimics the specific site in TRPV1 (aa 701-709: Gln-Arg-Ala-Ile-Thr-Ile-Leu-Asp-Thr, QRAITILDT), Thr 705 , and tested its efficacy of blocking UV-induced responses in HaCaT, mouse, and human skin. TIP effectively inhibited capsaicin-induced calcium influx and TRPV1 activation. Treatment of HaCaT with TIP prevented UV-induced increases of MMP-1 and pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor-α. In mouse skin in vivo, TIP inhibited UV-induced skin thickening and prevented UV-induced expression of MMP-13 and MMP-9. Moreover, TIP attenuated UV-induced erythema and the expression of MMP-1, MMP-2, IL-6, and IL-8 in human skin in vivo. The novel synthetic peptide targeting TRPV1 can ameliorate UV-induced skin responses in vitro and in vivo, providing a promising therapeutic approach against UV-induced inflammation and photoaging. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

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

Energy Technology Data Exchange (ETDEWEB)

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

2015-05-15

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

Chemical peeling by SA-PEG remodels photo-damaged skin: suppressing p53 expression and normalizing keratinocyte differentiation.

Science.gov (United States)

Dainichi, Teruki; Amano, Satoshi; Matsunaga, Yukiko; Iriyama, Shunsuke; Hirao, Tetsuji; Hariya, Takeshi; Hibino, Toshihiko; Katagiri, Chika; Takahashi, Motoji; Ueda, Setsuko; Furue, Masutaka

2006-02-01

Chemical peeling with salicylic acid in polyethylene glycol vehicle (SA-PEG), which specifically acts on the stratum corneum, suppresses the development of skin tumors in UVB-irradiated hairless mice. To elucidate the mechanism through which chemical peeling with SA-PEG suppresses skin tumor development, the effects of chemical peeling on photodamaged keratinocytes and cornified envelopes (CEs) were evaluated in vivo. Among UVB-irradiated hairless mice, the structural atypia and expression of p53 protein in keratinocytes induced by UVB irradiation were intensely suppressed in the SA-PEG-treated mice 28 days after the start of weekly SA-PEG treatments when compared to that in the control UVB-irradiated mice. Incomplete expression of filaggrin and loricrin in keratinocytes from the control mice was also improved in keratinocytes from the SA-PEG-treated mice. In photo-exposed human facial skin, immature CEs were replaced with mature CEs 4 weeks after treatment with SA-PEG. Restoration of photodamaged stratum corneum by treatment with SA-PEG, which may affect remodeling of the structural environment of the keratinocytes, involved the normalization of keratinocyte differentiation and suppression of skin tumor development. These results suggest that the stratum corneum plays a protective role against carcinogenesis, and provide a novel strategy for the prevention of photo-induced skin tumors.

Ability of PABA to protect mammalian skin from ultraviolet light-induced skin tumors and actinic damage

International Nuclear Information System (INIS)

Snyder, D.S.; May, M.

1975-01-01

Application of 5% para-aminobenzoic acid (PABA) to hairless mice one hour prior to ultraviolet light (UVL) irradiation will almost totally protect these animals from developing tumors induced by chronic exposure to UVL in the 290 to 320 nm range in conjunction with a chemical carcinogen. Mice exposed to UVL and not protected by PABA developed primarily squamous cell carcinomas. Two months after cessation of chronic UVL exposure, the non-PABA-treated irradiated mouse skin appeared thickened, yellow, and wrinkled while showing elevated DNA synthesis, hyperplasia, hypergranulosis, and increased amounts of elastotic material. The PABA-treated skin was grossly normal

Chemical peeling in ethnic skin: an update.

Science.gov (United States)

Salam, A; Dadzie, O E; Galadari, H

2013-10-01

With the growth of cosmetic dermatology worldwide, treatments that are effective against skin diseases and augment beauty without prolonged recovery periods, or exposing patients to the risks of surgery, are increasing in popularity. Chemical peels are a commonly used, fast, safe and effective clinic room treatment that may be used for cosmetic purposes, such as for fine lines and photoageing, but also as primary or adjunct therapies for acne, pigmentary disorders and scarring. Clinicians are faced with specific challenges when using peels on ethnic skin (skin of colour). The higher risk of postinflammatory dyschromias and abnormal scarring makes peels potentially disfiguring. Clinicians should therefore have a sound knowledge of the various peels available and their safety in ethnic skin. This article aims to review the background, classification, various preparations, indications, patient assessment and complications of using chemical peels in ethnic skin. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

Deletion of epidermal Rac1 inhibits HPV-8 induced skin papilloma formation and facilitates HPV-8- and UV-light induced skin carcinogenesis.

Science.gov (United States)

Deshmukh, Jayesh; Pofahl, Ruth; Pfister, Herbert; Haase, Ingo

2016-09-06

Overexpression and increased activity of the small Rho GTPase Rac1 has been linked to squamous cell carcinoma of the epidermis and mucosa in humans. Targeted deletion of Rac1 or inhibition of Rac1 activity in epidermal keratinocytes reduced papilloma formation in a chemical skin carcinogenesis mouse model. However, a potential role of Rac1 in HPV- and UV-light induced skin carcinogenesis has not been investigated so far, solar UV radiation being an important carcinogen to the skin.To investigate this, we deleted Rac1 or modulated its activity in mice with transgenic expression of Human papilloma virus type-8 (HPV-8) in epidermal keratinocytes. Our data show that inhibition or deletion of Rac1 results in reduced papilloma formation upon UV-irradiation with a single dose, whereas constitutive activation of Rac1 strongly increases papilloma frequency in these mice. Surprisingly, we observed that, upon chronic UV-irradiation, the majority of mice with transgenic expression of HPV-8 and epidermis specific Rac1 deletion developed squamous cell carcinomas. Taken together, our data show that Rac1 exerts a dual role in skin carcinogenesis: its activation is, on one hand, required for HPV-8- and UV-light induced papilloma formation but, on the other, suppresses the development of squamous cell carcinomas.

Impact of chemical peeling combined with negative pressure on human skin.

Science.gov (United States)

Kim, S J; Kang, I J; Shin, M K; Jeong, K H; Baek, J H; Koh, J S; Lee, S J

2016-10-01

In vivo changes in skin barrier function after chemical peeling with alpha hydroxyacids (AHAs) have been previously reported. However, the additional effects of physical treatment with chemical agents on skin barrier function have not been adequately studied. This study measured the degree of acute skin damage and the time required for skin barrier repair using non-invasive bioengineering methods in vivo with human skin to investigate the additional effect of a 4% AHA chemical jet accelerated at supersonic velocities. Thirteen female subjects (average age: 29.54 ± 4.86 years) participated in this study. The faces of the subjects were divided into half according to the block randomization design and were then assigned to receive AHA peeling alone or AHA peeling combined with pneumatic pressure on each side of the face. Transepidermal water loss (TEWL), skin colour and skin blood flow were evaluated at baseline and at 30 min, 2, 5 and 7 days after treatment. The TEWL and skin blood flow were significantly increased after 30 min in chemodermabrasion compared with chemical peeling alone (P peeling alone (P < 0.05). Chemodermabrasion can temporarily impair skin barriers, but it is estimated that it can enhance the skin barrier function after 7 days compared to the use of a chemical agent alone. In addition, chemodermabrasion has a more effective impact in the dermis and relatively preserves the skin barrier. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-02-01

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

Silibinin attenuates sulfur mustard analog-induced skin injury by targeting multiple pathways connecting oxidative stress and inflammation.

Directory of Open Access Journals (Sweden)

Neera Tewari-Singh

Full Text Available Chemical warfare agent sulfur mustard (HD inflicts delayed blistering and incapacitating skin injuries. To identify effective countermeasures against HD-induced skin injuries, efficacy studies were carried out employing HD analog 2-chloroethyl ethyl sulfide (CEES-induced injury biomarkers in skin cells and SKH-1 hairless mouse skin. The data demonstrate strong therapeutic efficacy of silibinin, a natural flavanone, in attenuating CEES-induced skin injury and oxidative stress. In skin cells, silibinin (10 µM treatment 30 min after 0.35/0.5 mM CEES exposure caused a significant (p90%, and activation of transcription factors NF-κB and AP-1 (complete reversal. Similarly, silibinin treatment was also effective in attenuating CEES-induced oxidative stress measured by 4-hydroxynonenal and 5,5-dimethyl-2-(8-octanoic acid-1-pyrolline N-oxide protein adduct formation, and 8-oxo-2-deoxyguanosine levels. Since our previous studies implicated oxidative stress, in part, in CEES-induced toxic responses, the reversal of CEES-induced oxidative stress and other toxic effects by silibinin in this study indicate its pleiotropic therapeutic efficacy. Together, these findings support further optimization of silibinin in HD skin toxicity model to develop a novel effective therapy for skin injuries by vesicants.

Damage and recovery of skin barrier function after glycolic acid chemical peeling and crystal microdermabrasion.

Science.gov (United States)

Song, Ji Youn; Kang, Hyun A; Kim, Mi-Yeon; Park, Young Min; Kim, Hyung Ok

2004-03-01

Superficial chemical peeling and microdermabrasion have become increasingly popular methods for producing facial rejuvenation. However, there are few studies reporting the skin barrier function changes after these procedures. To evaluate objectively the degree of damage visually and the time needed for the skin barrier function to recover after glycolic acid peeling and aluminum oxide crystal microdermabrasion using noninvasive bioengineering methods. Superficial chemical peeling using 30%, 50%, and 70% glycolic acid and aluminum oxide crystal microdermabrasion were used on the volar forearm of 13 healthy women. The skin response was measured by a visual observation and using an evaporimeter, corneometer, and colorimeter before and after peeling at set time intervals. Both glycolic acid peeling and aluminum oxide crystal microdermabrasion induced significant damage to the skin barrier function immediately after the procedure, and the degree of damage was less severe after the aluminum oxide crystal microdermabrasion compared with glycolic acid peeling. The damaged skin barrier function had recovered within 24 hours after both procedures. The degree of erythema induction was less severe after the aluminum oxide crystal microdermabrasion compared with the glycolic acid peeling procedure. The degree of erythema induced after the glycolic acid peeling procedure was not proportional to the peeling solution concentration used. The erythema subsided within 1 day after the aluminum oxide crystal microdermabrasion procedure and within 4 days after the glycolic acid peeling procedure. These results suggest that the skin barrier function is damaged after the glycolic acid peeling and aluminum oxide crystal microdermabrasion procedure but recovers within 1 to 4 days. Therefore, repeating the superficial peeling procedure at 2-week intervals will allow sufficient time for the damaged skin to recover its barrier function.

Chemical Decontamination of Campylobacter jejuni on Chicken Skin and Meat

DEFF Research Database (Denmark)

Riedel, Charlotte Tandrup; Brøndsted, Lone; Rosenquist, Hanne

2009-01-01

This study evaluated the effectiveness of 11 chemical compounds to reduce Campylobacter jejuni on chicken skin and meat samples dipped in chemical solutions. Treatment of skin samples for 1 min using tartaric acid (2%) and caprylic acid sodium salt (5%) caused reductions of C. jejuni NCTC11168...... effective, indicating that some cells may recover after a 1-min treatment with these chemicals. An increase in treatment time to 15 min resulted in higher effectiveness of trisodium phosphate and formic acid. Interestingly, when reduction of the C. jejuni population was compared on chicken skin and meat...

Curcumin Protects Skin against UVB-Induced Cytotoxicity via the Keap1-Nrf2 Pathway: The Use of a Microemulsion Delivery System

Directory of Open Access Journals (Sweden)

Maya Ben Yehuda Greenwald

2017-01-01

Full Text Available Curcumin was found to be beneficial in treating several skin pathologies and diseases, providing antioxidant protection due to its reducing properties and its electrophilic properties (the ability to activate the Nrf2 pathway and induce phase II cytoprotective enzymes. Nevertheless, clinical applications of curcumin are being hampered by its insufficient solubility, chemical instability, and poor absorption, leading to low efficacy in preventing skin pathologies. These limitations can be overcome by using a nanotechnology-based delivery system. Here, we elucidated the possibility of using curcumin encapsulated in a microemulsion preserving its unique chemical structure. We also examined whether curcumin microemulsion would reduce UVB-induced toxicity in skin. A significant curcumin concentration was found in the human skin dermis following topical application of a curcumin microemulsion. Moreover, curcumin microemulsion enhanced the reduction of UV-induced cytotoxicity in epidermal cells, paving the way for other incorporated electrophiles in encapsulated form protecting skin against stress-related diseases.

Curcumin Protects Skin against UVB-Induced Cytotoxicity via the Keap1-Nrf2 Pathway: The Use of a Microemulsion Delivery System

Science.gov (United States)

Ben Yehuda Greenwald, Maya; Frušić-Zlotkin, Marina; Soroka, Yoram; Ben Sasson, Shmuel; Bitton, Ronit; Bianco-Peled, Havazelet

2017-01-01

Curcumin was found to be beneficial in treating several skin pathologies and diseases, providing antioxidant protection due to its reducing properties and its electrophilic properties (the ability to activate the Nrf2 pathway and induce phase II cytoprotective enzymes). Nevertheless, clinical applications of curcumin are being hampered by its insufficient solubility, chemical instability, and poor absorption, leading to low efficacy in preventing skin pathologies. These limitations can be overcome by using a nanotechnology-based delivery system. Here, we elucidated the possibility of using curcumin encapsulated in a microemulsion preserving its unique chemical structure. We also examined whether curcumin microemulsion would reduce UVB-induced toxicity in skin. A significant curcumin concentration was found in the human skin dermis following topical application of a curcumin microemulsion. Moreover, curcumin microemulsion enhanced the reduction of UV-induced cytotoxicity in epidermal cells, paving the way for other incorporated electrophiles in encapsulated form protecting skin against stress-related diseases. PMID:28757910

Quercitrin protects skin from UVB-induced oxidative damage

Energy Technology Data Exchange (ETDEWEB)

Yin, Yuanqin [Cancer Institute, The First Affiliated Hospital, China Medical University, Shenyang (China); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Yao, Hua [Department of Stomatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang (China); Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J. [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Luo, Jia [Department of Internal Medicine, University of Kentucky, 800 Rose Street, Lexington, KY (United States); Gao, Ning [Department of Pharmacognos, College of Pharmacy, 3rd Military Medical University, Chongqing (China); Shi, Xianglin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States)

2013-06-01

Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. - Highlights: • Oxidative stress plays a key role in UV-induced cell and tissue injuries. • Quercitrin decreases ROS generation and restores antioxidants irradiated by UVB. • Quercitrin reduces UVB-irradiated oxidative DNA damage, apoptosis, and inflammation. • Quercitrin functions as an antioxidant against UVB-induced skin injuries.

Quercitrin protects skin from UVB-induced oxidative damage

International Nuclear Information System (INIS)

Yin, Yuanqin; Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin; Yao, Hua; Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J.; Luo, Jia; Gao, Ning; Shi, Xianglin; Zhang, Zhuo

2013-01-01

Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. - Highlights: • Oxidative stress plays a key role in UV-induced cell and tissue injuries. • Quercitrin decreases ROS generation and restores antioxidants irradiated by UVB. • Quercitrin reduces UVB-irradiated oxidative DNA damage, apoptosis, and inflammation. • Quercitrin functions as an antioxidant against UVB-induced skin injuries

Chemical ecology of interactions between human skin microbiota and mosquitoes

NARCIS (Netherlands)

Verhulst, N.O.; Takken, W.; Dicke, M.; Schraa, G.; Smallegange, R.C.

2010-01-01

Microbiota on the human skin plays a major role in body odour production. The human microbial and chemical signature displays a qualitative and quantitative correlation. Genes may influence the chemical signature by shaping the composition of the microbiota. Recent studies on human skin microbiota,

Attachment-inducing capacities of fish skin epithelial extracts on oncomiracidia of Benedenia seriolae (Monogenea: Capsalidae).

Science.gov (United States)

Yoshinaga, Tomoyoshi; Nagakura, Tatsuhiro; Ogawa, Kazuo; Fukuda, Yutaka; Wakabayashi, Hisatsugu

2002-03-01

Attachment-inducing capacities of skin epithelial extracts of yellowtail, Japanese flounder and red sea bream on oncomiracidia of the monogenean Benedenia seriolae were examined. Clear differences were not detected in the capacity among the fish species, although B. seriolae infects only yellowtail and its congeners in Seriola. This suggests that either the capacity is not host specific or host-specific attachment-inducing capacity cannot be detected by the assay method. Further, the attachment-inducing capacities were suppressed by wheat-germ lectin and concanavalin A in skin epithelial extracts of Japanese flounder and yellowtail, respectively. This suggests that some sugar-related chemical substances existing in fish epithelia induce the attachment of B. seriolae oncomiracidia.

Histological case-control study of peeling-induced skin changes by different peeling agents in surgically subcutaneous undermined skin flaps in facelift patients.

Science.gov (United States)

Gonser, P; Kaestner, S; Jaminet, P; Kaye, K

2017-11-01

A histological evaluation of peeling-induced skin changes in subcutaneous undermined preauricular facial skin flaps of nine patients was performed. There were three treatment groups: Trichloroacetic acid (TCA) 25%, TCA 40% and phenol/croton oil; one group served as control. Two independent evaluators determined the epidermal and dermal thickness and the depth of necrosis (micrometre). The percentual tissue damage due to the peeling was calculated, and a one-sample t-test for statistical significance was performed. On the basis of the histomorphological changes, peeling depth was classified as superficial, superficial-partial, deep-partial and full thickness chemical burn. The histological results revealed a progression of wound depth for different peeling agents without full thickness necrosis. TCA peels of up to 40% can be safely applied on subcutaneous undermined facial skin flaps without impairing the vascular patency, producing a predictable chemical burn, whereas deep peels such as phenol/croton oil peels should not be applied on subcutaneous undermined skin so as to not produce skin slough or necrosis by impairing vascular patency. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

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

Energy Technology Data Exchange (ETDEWEB)

Mouret, Stéphane, E-mail: stephane.mouret@irba.fr [Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, Centre de Recherches du Service de Santé des Armées, 24 avenue Maquis du Grésivaudan, 38700 La Tronche (France); Wartelle, Julien; Emorine, Sandy; Bertoni, Marine; Nguon, Nina; Cléry-Barraud, Cécile [Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, Centre de Recherches du Service de Santé des Armées, 24 avenue Maquis du Grésivaudan, 38700 La Tronche (France); Dorandeu, Frédéric [Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, Centre de Recherches du Service de Santé des Armées, 24 avenue Maquis du Grésivaudan, 38700 La Tronche (France); Ecole du Val-de-Grâce, 1 place Alphonse Laveran, Paris (France); Boudry, Isabelle [Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, Centre de Recherches du Service de Santé des Armées, 24 avenue Maquis du Grésivaudan, 38700 La Tronche (France)

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.

A case of radiation-induced skin ulcer, cerebral meningioma and skin cancer

International Nuclear Information System (INIS)

Matsuo, Yuki; Yano, Kenji

2000-01-01

We report a case of radiation-induced skin ulcer, cerebral meningioma, and skin cancer in a 69-year-old woman who had undergone local irradiation and application of radium directly to the skin for actinomycosis of the face at the age of twenty. Some forty to fifty years later, a skin ulcer in the preauricular area in the center of the radiodermatitis, cerebral meningioma in the right sphenoid ridge, and a keratotic skin tumor in the right auricle all developed within the previously irradiated region. The cerebral meningioma was extirpated. The skin ulcer was excised and covered with a forearm flap. After the skin tumor was excised and the subcutaneous tumor in the postauricular area was excised, the postoperative histopathological diagnosis was squamous cell carcinoma with lymph node metastasis. It was considered that the squamous cell carcinoma was derived from irradiated keratosis. Four months later, right neck lymph node dissection was performed. Both the meningioma and squamous cell carcinoma satisfied Cahan's criteria for radiation-induced tumors. So we diagnosed these as radiation-induced cerebral meningioma and squamous cell carcinoma. We haven't detected any recurrence of the squamous cell carcinoma for two years. We learned from this case that chronic radiation disturbances cause an irreversible reaction and various radiolesions, including malignancies, can occur after a long period of latency. It is important to never underestimate a small lesion in the irradiated area, to plan early preventive surgical treatment to remove skin that may have been over-subjected to irradiation, and to continue long-term follow-up for patients with chronic radiodermatitis. (author)

Skin lesions in Lorestan province chemically wounded combatants

Directory of Open Access Journals (Sweden)

roghaye Jebraili

2004-01-01

Findings: All of the studied cases with mean age of 39.26 years old had skin manifestations among which the most common symptoms were itching , burning ,dry skin , scaling. From view point of lesions, the most common signs were erythema (81% , excoriation (87.9% and pruritic papules (49.5%. Final diagnosis in 78% of the patients was chronic dermatitis and in 7.7% of them was seborrhoeic dermatitis and in 8.8% both chronic and seborrhoeic dermatitis were observed .During exposure to chemical gases only 37.9% of these combatants had used special masks and 40% had properly worn special clothes to protect themselves which covered their body completely , but rest of them had either used protection instruments improperly or had not used them at all. Most of the lesions were in trunk , lower extremities , abdomen , head and neck .78% of the cases had multiple lesions Conclusion: Regarding the results of this study all of the chemical wounded combatants of Lorestan province suffer from different degrees of skin lesions , although more than half of them were not aware of kind and nature of the chemical gases , but it is suggested to do further studies on long-term effects of these chemical gases.

Blue light-induced oxidative stress in live skin.

Science.gov (United States)

Nakashima, Yuya; Ohta, Shigeo; Wolf, Alexander M

2017-07-01

Skin damage from exposure to sunlight induces aging-like changes in appearance and is attributed to the ultraviolet (UV) component of light. Photosensitized production of reactive oxygen species (ROS) by UVA light is widely accepted to contribute to skin damage and carcinogenesis, but visible light is thought not to do so. Using mice expressing redox-sensitive GFP to detect ROS, blue light could produce oxidative stress in live skin. Blue light induced oxidative stress preferentially in mitochondria, but green, red, far red or infrared light did not. Blue light-induced oxidative stress was also detected in cultured human keratinocytes, but the per photon efficacy was only 25% of UVA in human keratinocyte mitochondria, compared to 68% of UVA in mouse skin. Skin autofluorescence was reduced by blue light, suggesting flavins are the photosensitizer. Exposing human skin to the blue light contained in sunlight depressed flavin autofluorescence, demonstrating that the visible component of sunlight has a physiologically significant effect on human skin. The ROS produced by blue light is probably superoxide, but not singlet oxygen. These results suggest that blue light contributes to skin aging similar to UVA. Copyright © 2017 Elsevier Inc. All rights reserved.

A case of radiation-induced skin ulcer, cerebral meningioma and skin cancer

Energy Technology Data Exchange (ETDEWEB)

Matsuo, Yuki; Yano, Kenji [Kure National Hospital, Hiroshima (Japan)

2000-10-01

We report a case of radiation-induced skin ulcer, cerebral meningioma, and skin cancer in a 69-year-old woman who had undergone local irradiation and application of radium directly to the skin for actinomycosis of the face at the age of twenty. Some forty to fifty years later, a skin ulcer in the preauricular area in the center of the radiodermatitis, cerebral meningioma in the right sphenoid ridge, and a keratotic skin tumor in the right auricle all developed within the previously irradiated region. The cerebral meningioma was extirpated. The skin ulcer was excised and covered with a forearm flap. After the skin tumor was excised and the subcutaneous tumor in the postauricular area was excised, the postoperative histopathological diagnosis was squamous cell carcinoma with lymph node metastasis. It was considered that the squamous cell carcinoma was derived from irradiated keratosis. Four months later, right neck lymph node dissection was performed. Both the meningioma and squamous cell carcinoma satisfied Cahan's criteria for radiation-induced tumors. So we diagnosed these as radiation-induced cerebral meningioma and squamous cell carcinoma. We haven't detected any recurrence of the squamous cell carcinoma for two years. We learned from this case that chronic radiation disturbances cause an irreversible reaction and various radiolesions, including malignancies, can occur after a long period of latency. It is important to never underestimate a small lesion in the irradiated area, to plan early preventive surgical treatment to remove skin that may have been over-subjected to irradiation, and to continue long-term follow-up for patients with chronic radiodermatitis. (author)

Facial reconstruction for radiation-induced skin cancer

International Nuclear Information System (INIS)

Panje, W.R.; Dobleman, T.J.

1990-01-01

Radiation-induced skin cancers can be difficult to diagnose and treat. Typically, a patient who has received orthovoltage radiotherapy for disorders such as acne, eczema, tinea capitis, skin tuberculosis, and skin cancer can expect that aggressive skin cancers and chronic radiodermatitis may develop subsequently. Cryptic facial cancers can lead to metastases and death. Prophylactic widefield excision of previously irradiated facial skin that has been subject to multiple recurrent skin cancers is suggested as a method of deterring future cutaneous malignancy and metastases. The use of tissue expanders and full-thickness skin grafts offers an expedient and successful method of subsequent reconstruction

Sunburn, Thermal, and Chemical Injuries to the Skin.

Science.gov (United States)

Monseau, Aaron J; Reed, Zebula M; Langley, Katherine Jane; Onks, Cayce

2015-12-01

Sunburn, thermal, and chemical injuries to the skin are common in the United States and worldwide. Initial management is determined by type and extent of injury with special care to early management of airway, breathing, and circulation. Fluid management has typically been guided by the Parkland formula, whereas some experts now question this. Each type of skin injury has its own pathophysiology and resultant complications. All primary care physicians should have at least a basic knowledge of management of acute and chronic skin injuries. Copyright © 2015 Elsevier Inc. All rights reserved.

Pyruvate metabolism: A therapeutic opportunity in radiation-induced skin injury

Energy Technology Data Exchange (ETDEWEB)

Yoo, Hyun; Kang, Jeong Wook [Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Lee, Dong Won [Department of Plastic Surgery, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Oh, Sang Ho [Department of Dermatology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Lee, Yun-Sil [College of Pharmacy & Division of Life and Pharmaceutical Sciences, Ewah Womans University, Seoul 120-750 (Korea, Republic of); Lee, Eun-Jung [Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Cho, Jaeho, E-mail: jjhmd@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

2015-05-08

Ionizing radiation is used to treat a range of cancers. Despite recent technological progress, radiation therapy can damage the skin at the administration site. The specific molecular mechanisms involved in this effect have not been fully characterized. In this study, the effects of pyruvate, on radiation-induced skin injury were investigated, including the role of the pyruvate dehydrogenase kinase 2 (PDK2) signaling pathway. Next generation sequencing (NGS) identified a wide range of gene expression differences between the control and irradiated mice, including reduced expression of PDK2. This was confirmed using Q-PCR. Cell culture studies demonstrated that PDK2 overexpression and a high cellular pyruvate concentration inhibited radiation-induced cytokine expression. Immunohistochemical studies demonstrated radiation-induced skin thickening and gene expression changes. Oral pyruvate treatment markedly downregulated radiation-induced changes in skin thickness and inflammatory cytokine expression. These findings indicated that regulation of the pyruvate metabolic pathway could provide an effective approach to the control of radiation-induced skin damage. - Highlights: • The effects of radiation on skin thickness in mice. • Next generation sequencing revealed that radiation inhibited pyruvate dehydrogenase kinase 2 expression. • PDK2 inhibited irradiation-induced cytokine gene expression. • Oral pyruvate treatment markedly downregulated radiation-induced changes in skin thickness.

EGFR Activation and Ultraviolet Light‐Induced Skin Carcinogenesis

Directory of Open Access Journals (Sweden)

Taghrid B. El-Abaseri

2007-01-01

Full Text Available The epidermal growth factor receptor (EGFR regulates the proliferation of keratinocytes through multiple mechanisms that differ depending on the localization of the cell within the skin. Ultraviolet (UV irradiation, the main etiologic factor in the development of skin cancer, also activates the receptor. In this review, we discuss how the UV-induced activation of EGFR regulates the response of the skin to UV. UV-induced EGFR activation increases keratinocyte proliferation, suppresses apoptosis, and augments and accelerates epidermal hyperplasia in response to UV. Pharmacological inhibition of the UV-induced activation of EGFR in a genetically initiated mouse skin tumorigenesis model suppresses tumorigenesis and the activation of mitogen-activated protein (MAP kinases and phosphatidyl inositol-3-kinase (PI3K/AKT signaling pathways. EGFR has pleiotropic, complex, and cell-type-specific functions in cutaneous keratinocytes; suggesting that the receptor is an appropriate target for the development of molecularly targeted therapies for skin cancer and other pathologies.

Correlation of initiating potency of skin carcinogens with potency to induce resistance to terminal differentiation in cultured mouse keratinocytes

International Nuclear Information System (INIS)

Kilkenny, A.E.; Morgan, D.; Spangler, E.F.; Yuspa, S.H.

1985-01-01

The induction by chemical carcinogens of resistance to terminal differentiation in cultured mouse keratinocytes has been proposed to represent a cellular change associated with the initiation phase of skin carcinogenesis. Previous results with this culture model indicated that the number of differentiation-resistant foci was correlated with the dose and known potency for several chemical carcinogens. Assay conditions were optimized to provide quantitative results for screening a variety of carcinogens for their potency as inducers of foci resistant to terminal differentiation. Eight skin initiators of varying potency and from different chemical classes and ultraviolet light were studied for their activity to induce this alteration in cultured epidermal cells from newborn BALB/c mice. There was an excellent positive correlation for the potency of these agents as initiators in vivo and as inducers of altered differentiation in vitro. The induction of resistant foci was independent of the relative cytotoxic effects of each agent except where cytotoxicity was extensive and reduced the number of foci. The results support the hypothesis that initiation of carcinogenesis in skin results in an alteration in the program of epidermal cell differentiation. The results also suggest that the assay is useful for identifying relative potency classes (strong, moderate, weak) of initiating agents

The pilosebaceous unit—a phthalate-induced pathway to skin sensitization

International Nuclear Information System (INIS)

Simonsson, Carl; Stenfeldt, Anna-Lena; Karlberg, Ann-Therese; Ericson, Marica B.; Jonsson, Charlotte A.M.

2012-01-01

Allergic contact dermatitis (ACD) is caused by low-molecular weight compounds called haptens. It has been shown that the potency of haptens can depend on the formulation in which they are applied on the skin. Specifically the sensitization potency of isothiocyanates, a group of haptens which can be released from e.g. adhesive tapes and neoprene materials, increases with the presence of phthalates; however, the underlying mechanisms are not clear. A better understanding of the mechanisms governing the potency of haptens is important, e.g. to improve the risk assessment and the formulation of chemicals in consumer products. In this study we have explored phthalate-induced effects on the sensitization potency, skin distribution, and reactivity of fluorescent model isothiocyanate haptens using non-invasive two-photon microscopy to provide new insights regarding vehicle effects in ACD. The data presented in this paper indicate that the sensitization potency of isothiocyanates increases when applied in combination with dibutylphthalate due to a specific uptake via the pilosebaceous units. The results highlight the importance of shunt pathways when evaluating the bioavailability of skin sensitizers. The findings also indicate that vehicle-dependent hapten reactivity towards stratum corneum proteins regulates the bioavailability, and thus the potency, of skin sensitizers. -- Highlights: ► Vehicle effects on sensitization potency were investigated in the LLNA. ► In vivo cutaneous absorption of contact sensitizers was visualized using TPM. ► Sensitizing potency of isothiocyanates depends on the presence of a phthalate. ► Phthalate induced cutaneous absorption via the pilosebaceous units. ► Vehicle-dependent reactivity regulates sensitization potency.

The pilosebaceous unit—a phthalate-induced pathway to skin sensitization

Energy Technology Data Exchange (ETDEWEB)

Simonsson, Carl, E-mail: carl.simonsson@chem.gu.se [Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96, Gothenburg (Sweden); Stenfeldt, Anna-Lena; Karlberg, Ann-Therese [Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96, Gothenburg (Sweden); Ericson, Marica B., E-mail: marica.ericson@physics.gu.se [Department of Physics, University of Gothenburg, SE-412 96, Gothenburg (Sweden); Jonsson, Charlotte A.M. [Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96, Gothenburg (Sweden)

2012-10-01

Allergic contact dermatitis (ACD) is caused by low-molecular weight compounds called haptens. It has been shown that the potency of haptens can depend on the formulation in which they are applied on the skin. Specifically the sensitization potency of isothiocyanates, a group of haptens which can be released from e.g. adhesive tapes and neoprene materials, increases with the presence of phthalates; however, the underlying mechanisms are not clear. A better understanding of the mechanisms governing the potency of haptens is important, e.g. to improve the risk assessment and the formulation of chemicals in consumer products. In this study we have explored phthalate-induced effects on the sensitization potency, skin distribution, and reactivity of fluorescent model isothiocyanate haptens using non-invasive two-photon microscopy to provide new insights regarding vehicle effects in ACD. The data presented in this paper indicate that the sensitization potency of isothiocyanates increases when applied in combination with dibutylphthalate due to a specific uptake via the pilosebaceous units. The results highlight the importance of shunt pathways when evaluating the bioavailability of skin sensitizers. The findings also indicate that vehicle-dependent hapten reactivity towards stratum corneum proteins regulates the bioavailability, and thus the potency, of skin sensitizers. -- Highlights: ► Vehicle effects on sensitization potency were investigated in the LLNA. ► In vivo cutaneous absorption of contact sensitizers was visualized using TPM. ► Sensitizing potency of isothiocyanates depends on the presence of a phthalate. ► Phthalate induced cutaneous absorption via the pilosebaceous units. ► Vehicle-dependent reactivity regulates sensitization potency.

Moist skin care can diminish acute radiation-induced skin toxicity

International Nuclear Information System (INIS)

Momm, F.; Weissenberger, C.; Bertelt, S.; Henke, M.

2003-01-01

Background: Radiation treatment may induce acute skin reactions. There are several methods of managing them. Validity of these methods, however, is not sufficiently studied. We therefore investigated, whether moist skin care with 3% urea lotion will reduce acute radiation skin toxicity. Patients and Methods: 88 patients with carcinomas of the head and neck undergoing radiotherapy with curative intent (mean total dose 60 Gy, range: 50-74 Gy) were evaluated weekly for acute skin reactions according to the RTOG-CTC score. In 63 patients, moist skin care with 3% urea lotion was performed. The control group consisted of 25 patients receiving conventional dry skin care. The incidence of grade I, II, and III reactions and the radiation dose at occurrence of a particular reaction were determined and statistically analyzed using the log-rank test. The dose-time relations of individual skin reactions are described. Results: At some point of time during radiotherapy, all patients suffered from acute skin reactions grade I, > 90% from grade II reactions. 50% of patients receiving moist skin care experienced grade I reactions at 26 Gy as compared to 22 Gy in control patients (p = 0.03). Grade II reactions occurred at 51 Gy versus 34 Gy (p = 0.006). Further, 22% of the patients treated with moist skin care suffered from acute skin toxicity grade III as compared to 56% of the controls (p = 0.0007). Conclusion: Moist skin care with 3% urea lotion delays the occurrence and reduces the grade of acute skin reactions in percutaneously irradiated patients with head and neck tumors. (orig.)

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

Energy Technology Data Exchange (ETDEWEB)

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

2013-02-15

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

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

International Nuclear Information System (INIS)

Xia, Xiaojun; Park, Eunmi; Fischer, Susan M.; Hu, Yinling

2013-01-01

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

Type I allergy to natural rubber latex and type IV allergy to rubber chemicals in health care workers with glove-related skin symptoms.

Science.gov (United States)

Nettis, E; Assennato, G; Ferrannini, A; Tursi, A

2002-03-01

It has been established that there are type I and type IV allergens in latex gloves. The purpose of the study was to establish the prevalence of rubber glove-induced skin symptoms among health care workers in one Italian hospital. Health care workers (n = 1584) were evaluated using a written questionnaire and 295 respondents with glove-induced skin symptoms were tested. We performed: skin prick test with latex glove extract and commercial latex, and environmental and food allergens; glove use test; patch tests with a rubber additive series; and RASTs. Hospital employees who used or had used latex gloves at work were 1294. Three hundred and sixteen (24.4%) reported glove-induced symptoms, namely, cutaneous symptoms in all the cases and non-cutaneous symptoms in 105 subjects (8.1%). Twenty-seven of the 295 symptomatic employees tested (9.1%) were latex sensitive. Thirty-one patients (10.5%) exhibited positive patch test to rubber-related allergens. The most positive readings were obtained from the Thiuram mix and the Carba mix, with 12 and 9 positivities, respectively. The risk factors for latex skin sensitization were: a previous history of atopy and asthma; history of surgery; pre-existing hand dermatitis; work-related symptoms; and positive skin tests to common inhalant and certain foods (P skin complaints of latex gloves are related to skin irritation rather than to allergy. The immediate allergy to latex and the delayed allergy to rubber chemicals suggest that all the health care workers with glove-related dermatitis should undergo both skin prick test and glove use test to detect type I hypersensitivity to latex, and patch test to detect type IV hypersensitivity to rubber chemicals.

Skin absorption through atopic dermatitis skin

DEFF Research Database (Denmark)

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

2017-01-01

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

Erlotinib-induced rash spares previously irradiated skin

International Nuclear Information System (INIS)

Lips, Irene M.; Vonk, Ernest J.A.; Koster, Mariska E.Y.; Houwing, Ronald H.

2011-01-01

Erlotinib is an epidermal growth factor receptor inhibitor prescribed to patients with locally advanced or metastasized non-small cell lung carcinoma after failure of at least one earlier chemotherapy treatment. Approximately 75% of the patients treated with erlotinib develop acneiform skin rashes. A patient treated with erlotinib 3 months after finishing concomitant treatment with chemotherapy and radiotherapy for non-small cell lung cancer is presented. Unexpectedly, the part of the skin that had been included in his previously radiotherapy field was completely spared from the erlotinib-induced acneiform skin rash. The exact mechanism of erlotinib-induced rash sparing in previously irradiated skin is unclear. The underlying mechanism of this phenomenon needs to be explored further, because the number of patients being treated with a combination of both therapeutic modalities is increasing. The therapeutic effect of erlotinib in the area of the previously irradiated lesion should be assessed. (orig.)

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

International Nuclear Information System (INIS)

Yourick, Jeffrey J.; Koenig, Michael L.; Yourick, Debra L.; Bronaugh, Robert L.

2004-01-01

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

Epidermal Rac1 regulates the DNA damage response and protects from UV-light-induced keratinocyte apoptosis and skin carcinogenesis

Science.gov (United States)

Deshmukh, Jayesh; Pofahl, Ruth; Haase, Ingo

2017-01-01

Non-melanoma skin cancer (NMSC) is the most common type of cancer. Increased expression and activity of Rac1, a small Rho GTPase, has been shown previously in NMSC and other human cancers; suggesting that Rac1 may function as an oncogene in skin. DMBA/TPA skin carcinogenesis studies in mice have shown that Rac1 is required for chemically induced skin papilloma formation. However, UVB radiation by the sun, which causes DNA damage, is the most relevant cause for NMSC. A potential role of Rac1 in UV-light-induced skin carcinogenesis has not been investigated so far. To investigate this, we irradiated mice with epidermal Rac1 deficiency (Rac1-EKO) and their controls using a well-established protocol for long-term UV-irradiation. Most of the Rac1-EKO mice developed severe skin erosions upon long-term UV-irradiation, unlike their controls. These skin erosions in Rac1-EKO mice healed subsequently. Surprisingly, we observed development of squamous cell carcinomas (SCCs) within the UV-irradiation fields. This shows that the presence of Rac1 in the epidermis protects from UV-light-induced skin carcinogenesis. Short-term UV-irradiation experiments revealed increased UV-light-induced apoptosis of Rac1-deficient epidermal keratinocytes in vitro as well as in vivo. Further investigations using cyclobutane pyrimidine dimer photolyase transgenic mice revealed that the observed increase in UV-light-induced keratinocyte apoptosis in Rac1-EKO mice is DNA damage dependent and correlates with caspase-8 activation. Furthermore, Rac1-deficient keratinocytes showed reduced levels of p53, γ-H2AX and p-Chk1 suggesting an attenuated DNA damage response upon UV-irradiation. Taken together, our data provide direct evidence for a protective role of Rac1 in UV-light-induced skin carcinogenesis and keratinocyte apoptosis probably through regulating mechanisms of the DNA damage response and repair pathways. PMID:28277539

Epidermal Rac1 regulates the DNA damage response and protects from UV-light-induced keratinocyte apoptosis and skin carcinogenesis.

Science.gov (United States)

Deshmukh, Jayesh; Pofahl, Ruth; Haase, Ingo

2017-03-09

Non-melanoma skin cancer (NMSC) is the most common type of cancer. Increased expression and activity of Rac1, a small Rho GTPase, has been shown previously in NMSC and other human cancers; suggesting that Rac1 may function as an oncogene in skin. DMBA/TPA skin carcinogenesis studies in mice have shown that Rac1 is required for chemically induced skin papilloma formation. However, UVB radiation by the sun, which causes DNA damage, is the most relevant cause for NMSC. A potential role of Rac1 in UV-light-induced skin carcinogenesis has not been investigated so far. To investigate this, we irradiated mice with epidermal Rac1 deficiency (Rac1-EKO) and their controls using a well-established protocol for long-term UV-irradiation. Most of the Rac1-EKO mice developed severe skin erosions upon long-term UV-irradiation, unlike their controls. These skin erosions in Rac1-EKO mice healed subsequently. Surprisingly, we observed development of squamous cell carcinomas (SCCs) within the UV-irradiation fields. This shows that the presence of Rac1 in the epidermis protects from UV-light-induced skin carcinogenesis. Short-term UV-irradiation experiments revealed increased UV-light-induced apoptosis of Rac1-deficient epidermal keratinocytes in vitro as well as in vivo. Further investigations using cyclobutane pyrimidine dimer photolyase transgenic mice revealed that the observed increase in UV-light-induced keratinocyte apoptosis in Rac1-EKO mice is DNA damage dependent and correlates with caspase-8 activation. Furthermore, Rac1-deficient keratinocytes showed reduced levels of p53, γ-H2AX and p-Chk1 suggesting an attenuated DNA damage response upon UV-irradiation. Taken together, our data provide direct evidence for a protective role of Rac1 in UV-light-induced skin carcinogenesis and keratinocyte apoptosis probably through regulating mechanisms of the DNA damage response and repair pathways.

Noxious heat and scratching decrease histamine-induced itch and skin blood flow.

Science.gov (United States)

Yosipovitch, Gil; Fast, Katharine; Bernhard, Jeffrey D

2005-12-01

The aim of this study was to assess the effect of thermal stimuli or distal scratching on skin blood flow and histamine-induced itch in healthy volunteers. Twenty-one healthy volunteers participated in the study. Baseline measurements of skin blood flow were obtained on the flexor aspect of the forearm. These measurements were compared with skin blood flow after various stimuli: heating the skin, cooling the skin, noxious cold 2 degrees C, noxious heat 49 degrees C, and scratching via a brush with controlled pressure. Afterwards histamine iontophoresis was performed and skin blood flow and itch intensity were measured immediately after the above-mentioned stimuli. Scratching reduced mean histamine-induced skin blood flow and itch intensity. Noxious heat pain increased basal skin blood flow but reduced histamine-induced maximal skin blood flow and itch intensity. Cold pain and cooling reduced itch intensity, but neither affected histamine-induced skin blood flow. Sub-noxious warming the skin did not affect the skin blood flow or itch intensity. These findings suggest that heat pain and scratching may inhibit itch through a neurogenic mechanism that also affects skin blood flow.

Reactive skin decontamination lotion (RSDL) for the decontamination of chemical warfare agent (CWA) dermal exposure.

Science.gov (United States)

Schwartz, M D; Hurst, C G; Kirk, M A; Reedy, S J D; Braue, E H

2012-08-01

Rapid decontamination of the skin is the single most important action to prevent dermal absorption of chemical contaminants in persons exposed to chemical warfare agents (CWA) and toxic industrial chemicals (TICs) as a result of accidental or intentional release. Chemicals on the skin may be removed by mechanical means through the use of dry sorbents or water. Recent interest in decontamination systems which both partition contaminants away from the skin and actively neutralize the chemical has led to the development of several reactive decontamination solutions. This article will review the recently FDA-approved Reactive Skin Decontamination Lotion (RSDL) and will summarize the toxicity and efficacy studies conducted to date. Evidence of RSDL's superior performance against vesicant and organophosphorus chemical warfare agents compared to water, bleach, and dry sorbents, suggests that RSDL may have a role in mass human exposure chemical decontamination in both the military and civilian arenas.

Effects of magnolol on UVB-induced skin cancer development in mice and its possible mechanism of action

International Nuclear Information System (INIS)

Chilampalli, Chandeshwari; Guillermo, Ruth; Zhang, Xiaoying; Kaushik, Radhey S; Young, Alan; Zeman, David; Hildreth, Michael B; Fahmy, Hesham; Dwivedi, Chandradhar

2011-01-01

Magnolol, a plant lignan isolated from the bark and seed cones of Magnolia officinalis, has been shown to have chemopreventive effects on chemically-induced skin cancer development. The objectives of this investigation are to study the anticarcinogenic effects of magnolol on UVB-induced skin tumor development in SKH-1 mice, a model relevant to humans, and determine the possible role of apoptosis and cell cycle arrest involved in the skin tumor development. UVB-induced skin carcinogenesis model in SKH-1 mice was used for determining the preventive effects of magnolol on skin cancer development. Western blottings and flow cytometric analysis were used to study the effects of magnolol on apoptosis and cell cycle. Magnolol pretreated groups (30, 60 μ g) before UVB treatments (30 mJ/cm 2 , 5 days/week) resulted in 27-55% reduction in tumor multiplicity as compared to control group in SKH-1 mice. Magnolol pretreatment increased the cleavage of caspase-8 and poly-(-ADP-ribose) polymerase (PARP), increased the expression of p21, a cell cycle inhibitor, and decreased the expression of proteins involved in the G2/M phase of cell cycle in skin samples from SKH-1 mice. Treatment of A431 cells with magnolol decreased cell viability and cell proliferation in a concentration dependent manner. Magnolol induced G2/M phase cell cycle arrest in A431 cells at 12 h with a decreased expression of cell cycle proteins such as cyclin B1, cyclin A, CDK4, Cdc2 and simultaneous increase in the expression of Cip/p21, a cyclin-dependent kinase inhibitor. Magnolol induced apoptosis in vivo and in vitro with an increased cleavage of caspase-8 and PARP. Phospho-signal transducers and activators of transcription 3 (Tyr 705 ), B-Raf, p-MEK, and p-AKT were down-regulated, whereas phosphorylation of ERK was induced by magnolol in A431 cells. Magnolol pretreatments prevent UVB-induced skin cancer development by enhancing apoptosis, causing cell cycle arrest at G2/M phase, and affecting various

The role of natural and UV-induced skin pigmentation on low-fluence IPL-induced side effects

DEFF Research Database (Denmark)

Thaysen-Petersen, Daniel; Lin, Jennifer Y; Nash, Jf

2014-01-01

BACKGROUND AND OBJECTIVES: The risk of adverse skin effects following light-based hair removal is greater in pigmented skin based on the theory of selective photothermolysis. Thus sunlight-induced pigment i.e., facultative pigmentation, increases the risk of adverse skin effects, perhaps dispropo...... pigmentation regardless of the origin, i.e., constitutive versus UV induced....

Safety considerations to avoid current-induced skin burns in MRI

International Nuclear Information System (INIS)

Knopp, M.V.; Metzner, R.; Kaick, G. van; Brix, G.; Bundesamt fuer Strahlenschutz, Oberschleissheim

1998-01-01

The safety aspects of radiological methods continue to evolve. In this paper we report on two cases of skin burns in MRI caused by induced electrical current. A second- and a third-degree skin burn occurred during imaging in a 1.5 T system. The electromagnetic radiofrequency field inadvertently led to electrical currents caused by a conducting loop through the extremities and trunk. Skin burns induced by electrical current may occur in extremely rare cases even with standard MR imaging protocols operating within all current safety guidelines by inadvertently forming a closed conducting loop. By avoiding focal skin to skin contact of the extremities, this extremely rare adverse event can be avoided. (orig.) [de

The abdominal skin of female Sprague-Dawley rats is more sensitive than the back skin to drug-induced phototoxicity.

Science.gov (United States)

Kuga, Kazuhiro; Yasuno, Hironobu; Sakai, Yumi; Harada, Yumiko; Shimizu, Fumi; Miyamoto, Yumiko; Takamatsu, Yuki; Miyamoto, Makoto; Sato, Keiichiro

2017-11-01

In vivo phototoxicity studies are important to predict drug-induced phototoxicity in humans; however, a standard methodology has not established. To determine differences in sensitivity to drug-induced phototoxicity among various skin sites, we evaluated phototoxic reactions in the back and abdominal skin of female Sprague-Dawley rats orally dosed with phototoxic drugs (pirfenidone, 8-methoxysoraren, doxycycline, and lomefloxacin) or a non-phototoxic drug (gatifloxacin) followed by solar-simulated light irradiation comprising 18J/cm 2 ultraviolet A. Tissue reactions were evaluated by macroscopic and microscopic examination and immunohistochemistry for γ-H2AX, and tissue concentrations of pirfenidone, doxycycline, and lomefloxacin were measured by tandem mass spectrometry. In addition, the thicknesses of the skin layers at both sites were measured in drug-naïve rats. The abdominal skin showed more severe reactions to all phototoxic drugs than the back skin, whereas the minimal erythema dose in drug-naïve rats and skin concentrations of each drug were comparable between the sites. Furthermore, histopathological lesions and γ-H2AX-positive cells in the abdominal skin were detected in deeper layers than in the back skin. The stratum corneum and dermis in the abdominal skin were significantly thinner than in the back skin, indicating a difference in the depth of light penetration and potentially contributing to the site differences observed in sensitivity to phototoxicity. Gatifloxacin did not induce any phototoxic reactions at either site. In conclusion, the abdominal skin is more sensitive to drug-induced phototoxicity than the back skin and may represent a preferable site for irradiation in this rat phototoxicity model. Copyright © 2017 Elsevier Inc. All rights reserved.

Radiotherapy-Induced Skin Reactions Induce Fibrosis Mediated by TGF-β1 Cytokine

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Cherley Borba Vieira de Andrade

2017-04-01

Full Text Available Purpose: This study aimed to investigate radiation-induced lesions on the skin in an experimental animal model. Methods and Materials: Cutaneous wounds were induced in Wistar rats by 4 MeV energy electron beam irradiation, using a dose rate of 240 cGy/min, for 3 different doses (10 Gy, 40 Gy, and 60 Gy. The skin was observed 5, 10, and 25 days (D after ionizing radiation exposition. Results: Infiltrate inflammatory process was observed in D5 and D10, for the 40 Gy and 60 Gy groups, and a progressive increase of transforming growth factor β1 is associated with this process. It could also be noted a mischaracterization of collagen fibers at the high-dose groups. Conclusion: It was observed that the lesions caused by ionizing radiation in rats were very similar to radiodermatitis in patients under radiotherapy treatment. Advances in Knowledge: This study is important to develop strategies to prevent radiation-induced skin reactions.

Effect of heme oxygenase-1 on radiation-induced skin injury

International Nuclear Information System (INIS)

Song Chuanjun; Meng Xingjun; Xie Ling; Chen Qing; Zhou Jundong; Zhang Shuyu; Wu Jinchang

2012-01-01

Objective: To investigate the effect of heme oxygenase-1 (HO-1) on the acute radiation-induced skin injury by gene transfer. Methods: Thirty-three male SD rats were randomly divided into three groups as PBS-injected group, Ad-EGFP-injected group and Ad-HO-1-injected group (n=11). In each group, three rats were used for determining the expression of target gene and the other rats were irradiated on the buttock skin with 40 Gy electron beam generated by a linear accelerator. Immediately after irradiation, rats were administered with a subcutaneous injection of PBS, Ad-EGFP or Ad-HO-1, respectively. Subsequently, the skin reactions were measured twice a week using the semi-quantitative skin injury scale. Results: The strong positive expression of HO-1 was observed in subcutaneous dermal tissue after injection of Ad-HO-1. Compared to the PBS-injected group or the Ad-EGFP-injected group, a significant mitigation of skin injury was observed in Ad-HO-1-injected mice 14 d after irradiation (q=0.000-0.030, P<0.05). Conclusions: HO-1 could significantly mitigate radiation-induced acute skin injury and Ad-HO-1 could be used to treat radiation-induced skin injury. (authors)

THP-1 monocytes but not macrophages as a potential alternative for CD34+ dendritic cells to identify chemical skin sensitizers

International Nuclear Information System (INIS)

Lambrechts, Nathalie; Verstraelen, Sandra; Lodewyckx, Hanne; Felicio, Ana; Hooyberghs, Jef; Witters, Hilda; Tendeloo, Viggo van; Cauwenberge, Paul van; Nelissen, Inge; Heuvel, Rosette van den; Schoeters, Greet

2009-01-01

Early detection of the sensitizing potential of chemicals is an emerging issue for chemical, pharmaceutical and cosmetic industries. In our institute, an in vitro classification model for prediction of chemical-induced skin sensitization based on gene expression signatures in human CD34 + progenitor-derived dendritic cells (DC) has been developed. This primary cell model is able to closely mimic the induction phase of sensitization by Langerhans cells in the skin, but it has drawbacks, such as the availability of cord blood. The aim of this study was to investigate whether human in vitro cultured THP-1 monocytes or macrophages display a similar expression profile for 13 predictive gene markers previously identified in DC and whether they also possess a discriminating capacity towards skin sensitizers and non-sensitizers based on these marker genes. To this end, the cell models were exposed to 5 skin sensitizers (ammonium hexachloroplatinate IV, 1-chloro-2,4-dinitrobenzene, eugenol, para-phenylenediamine, and tetramethylthiuram disulfide) and 5 non-sensitizers (L-glutamic acid, methyl salicylate, sodium dodecyl sulfate, tributyltin chloride, and zinc sulfate) for 6, 10, and 24 h, and mRNA expression of the 13 genes was analyzed using real-time RT-PCR. The transcriptional response of 7 out of 13 genes in THP-1 monocytes was significantly correlated with DC, whereas only 2 out of 13 genes in THP-1 macrophages. After a cross-validation of a discriminant analysis of the gene expression profiles in the THP-1 monocytes, this cell model demonstrated to also have a capacity to distinguish skin sensitizers from non-sensitizers. However, the DC model was superior to the monocyte model for discrimination of (non-)sensitizing chemicals.

Radiation-induced cancer of the skin in man

International Nuclear Information System (INIS)

Kiyono, Kunihiro; Moriya, Kumiko; Kobayashi, Toshio

1981-01-01

Eight cases of radiation induced cancer of the skin observed at the Shinshu University during 30 years from 1951 to 1938 were reported. All of the tumors were squamous cell carcinomas; 7 out of 8 cases occurred in males. Primary conditions for which irradiation was given were 6 cases of benign disorders of various skin disease and 2 cases of spinal tuberculosis. The mean age at which these patients were first subjected to radiation therapy was 31 years. At the time when the diagnosis of skin cancer was established, the mean age was 47 years, with a range from 35 to 58 years. The latent period distributed between 9 and 28 years, with the average of 16.4 years. The estimated radiation doses sufficient to induce cancer of the skin was found to be some thousands R or more, the lowest irradiation dose being about 2,000 R. There was no close correlation between the radiation dose and the latent period, nor between the age of the patient at the time of irradiation and the latent period. The tumors usually occurred in the skin areas where extensive irradiation changes were shown, especially in ulcerative area. (author)

Protective molecular mechanisms of resveratrol in UVR-induced Skin carcinogenesis.

Science.gov (United States)

Aziz, Saba W; Aziz, Moammir H

2018-01-01

Skin cancer is a major health problem worldwide. It is the most common cancer in the United States and poses a significant healthcare burden. Excessive UVR exposure is the most common cause of skin cancer. Despite various precautionary measures to avoid direct UVR exposure, the incidence of skin cancer and mortality related to it remains high. Furthermore, the current treatment options are expensive and have side effects including toxicity to normal cells. Thus, a safe and effective approach is needed to prevent and treat skin cancer. Chemopreventive strategy using naturally occurring compounds, such as resveratrol, is a promising approach to reduce the incidence of UVR-induced skin cancer and delay its progression. This review highlights the current body of evidence related to chemopreventive role of resveratrol and its molecular mechanisms in UVR-induced skin carcinogenesis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Resveratrol anti-ultraviolet-induced guinea pig skin injury

International Nuclear Information System (INIS)

Li Wenxing; Zhao Ying

2014-01-01

Objective: To Estimate on the protection effect of Stilbene on skin damage induced by ultraviolet radiation. Methods: After the normal skin in guinea pig under the intervene of Resveratrol was irradiated with over- dose of ultraviolet rays (UVB and UVA), the samples in every group were matched and compared. Results: The skin tissue in the Resveratrol intervene group irradiated by ultraviolet rays didn't change obviously as compared with that in the self-control group. But, the damage skin tissue in the control group irradiated by ultraviolet did change significantly as compared with that in the Stilbene intervene group. Conclusion: Resveratrol is a good material to protect the skin from damage effect by ultraviolet radiation. (authors)

Effects of Depilation-Induced Skin Pigmentation and Diet-Induced Fluorescence on In Vivo Fluorescence Imaging

OpenAIRE

Kwon, Sunkuk; Sevick-Muraca, Eva M.

2017-01-01

Near-infrared fluorescence imaging (NIRFI) and far-red fluorescence imaging (FRFI) were used to investigate effects of depilation-induced skin pigmentation and diet-induced background fluorescence on fluorescent signal amplitude and lymphatic contraction frequency in C57BL6 mice. Far-red fluorescent signal amplitude, but not frequency, was affected by diet-induced fluorescence, which was removed by feeding the mice an alfalfa-free diet, and skin pigmentation further impacted the amplitude mea...

Let the sun shine in: mechanisms and potential for therapeutics in skin photodamage.

Science.gov (United States)

Wondrak, Georg T

2007-05-01

Photoaging and photocarcinogenesis are the two Janus faces of skin photodamage. Reactivity-based design of prototype agents that antagonize, modulate and reverse the chemistry of skin photodamage holds promise in delivering unprecedented therapeutic benefit. In contrast to structure-based approaches that use selective ligands to target macromolecules, reactivity-based drug discovery uses chemical reagents as therapeutics to target reactive chemical species as key mediators of skin photo-oxidative stress. The following classes of reactivity-based agents for skin photoprotection can be distinguished based on their mechanism of action: direct antagonists of photo-oxidative stress (sunscreens, quenchers of photo-excited states, antioxidants, redox modulators and glycation inhibitors) and skin photo-adaptation inducers (nuclear factor erythroid 2-related factor 2 [Nrf2] activators, heat-shock response inducers and metallothionein inducers).

JWA deficiency suppresses dimethylbenz[a]anthracene-phorbol ester induced skin papillomas via inactivation of MAPK pathway in mice.

Directory of Open Access Journals (Sweden)

Zhenghua Gong

Full Text Available Our previous studies indicated that JWA plays an important role in DNA damage repair, cell migration, and regulation of MAPKs. In this study, we investigated the role of JWA in chemical carcinogenesis using conditional JWA knockout (JWA(Δ2/Δ2 mice and two-stage model of skin carcinogenesis. Our results indicated that JWA(Δ2/Δ2 mice were resistant to the development of skin papillomas initiated by 7, 12-dimethylbenz(aanthracene (DMBA followed by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA. In JWA(Δ2/Δ2 mice, the induction of papilloma was delayed, and the tumor number and size were reduced. In primary keratinocytes from JWA(Δ2/Δ2 mice, DMBA exposure induced more intensive DNA damage, while TPA-promoted cell proliferation was reduced. The further mechanistic studies showed that JWA deficiency blocked TPA-induced activation of MAPKs and its downstream transcription factor Elk1 both in vitro and in vivo. JWA(Δ2/Δ2 mice are resistance to tumorigenesis induced by DMBA/TPA probably through inhibition of transcription factor Elk1 via MAPKs. These results highlight the importance of JWA in skin homeostasis and in the process of skin tumor development.

The physico-chemical properties of pangas catfish (Pangasius pangasius) skin gelatin

Science.gov (United States)

Pradarameswari, K. A.; Zaelani, K.; Waluyo, E.; Nurdiani, R.

2018-04-01

Gelatin can be used as emulsifier and stabilizer in food products. Until now, the most widely used raw materials for the production of gelatin industry are cow bone, cow skin and pig skin. Fish gelatin has been highlighted as a better alternative to replace mammals gelatin based on ethical and religious perspective. Fish gelatin was extracted from Pangas catfish skin to determine its physico-chemical properties. Different temperatures (45 °C, 50 °C, 55 °C) were employed during gelatin extraction. Higher temperature increased the yield and fat contents of Pangas catfish skin gelatin. In contrary, higher water, protein, ash contents were observed during lower temperature. Temperature significantly (p fish skin gelatin. Based on the FTIR spectrum catfish skin gelatin functional groups can be identified as N-H, O-H, C = H, C-O and C-H.

Skin manifestations of growth hormone-induced diseases.

Science.gov (United States)

Kanaka-Gantenbein, Christina; Kogia, Christina; Abdel-Naser, Mohamed Badawy; Chrousos, George P

2016-09-01

The human skin is a well-organized organ bearing different types of cells in a well-structured interference to each other including epidermal and follicular keratinocytes, sebocytes, melanocytes, dermal papilla cells and fibroblasts, endothelial cells, sweat gland cells as well as nerves. Several hormones act on different cell types of the skin, while it is also considered an endocrine organ secreting hormones that act at several sites of the organism. GH receptors are found in almost all cell types forming the skin, while IGF-1 receptors' expression is restricted to the epidermal keratinocytes. Both Growth Hormone (GH) excess, as in the case of Acromegaly in adults, or Gigantism in growing children, and GH deficiency states lead to skin manifestations. In case of GH excess the main dermatological findings are skin thickening, coarsening of facial features, acrochordons, puffy hands and feet, oily skin and hyperhidrosis, while GH deficiency, on the contrary, is characterized by thin, dry skin and disorder of normal sweating. Moreover, special disorders associated with GH excess may have specific characteristics, as is the case of café-au-lait spots in Neurofibromatosis, or big café-au-lait skin hyperpigmented regions with irregular margins, as is the case in McCune-Albright syndrome. Meticulous examination of the skin may therefore contribute to the final diagnosis in cases of GH-induced disorders.

The skin microbiome: Is it affected by UV-induced immune suppression?

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Vijaykumar Patra

2016-08-01

Full Text Available Human skin apart from functioning as a physical barricade to stop the entry of pathogens, also hosts innumerable commensal organisms. The skin cells and the immune system constantly interact with microbes, to maintain cutaneous homeostasis, despite the challenges offered by various environmental factors. A major environmental factor affecting the skin is ultraviolet radiation UV-R from sunlight. UV-R is well known to modulate the immune system, which can be both beneficial and deleterious. By targeting the cells and molecules within skin, UV-R can trigger the production and release of antimicrobial peptides (AMPs, affect the innate immune system and ultimately suppress the adaptive cellular immune response. This can contribute to skin carcinogenesis and the promotion of infectious agents such as herpes simplex virus and possibly others. On the other hand, a UV-established immunosuppressive environment may protect against the induction of immunologically mediated skin diseases including some of photodermatoses such as polymorphic light eruption. In this article, we share our perspective about the possibility that UV-induced immune suppression may alter the landscape of the skin's microbiome and its components. Alternatively, or in concert with this, direct UV-induced DNA and membrane damage to the microbiome may result in pathogen associated molecular patterns (PAMPs that interfere with UV-induced immune suppression.

Drug delivery strategies for chemoprevention of UVB-induced skin cancer: A review.

Science.gov (United States)

Bagde, Arvind; Mondal, Arindam; Singh, Mandip

2018-01-01

Annually, more skin cancer cases are diagnosed than the collective incidence of the colon, lung, breast, and prostate cancer. Persistent contact with sunlight is a primary cause for all the skin malignancies. UVB radiation induces reactive oxygen species (ROS) production in the skin which eventually leads to DNA damage and mutation. Various delivery approaches for the skin cancer treatment/prevention have been evolving and are directed toward improvements in terms of delivery modes, therapeutic agents, and site-specificity of therapeutics delivery. The effective chemoprevention activity achieved is based on the efficiency of the delivery system used and the amount of the therapeutic molecule deposited in the skin. In this article, we have discussed different studies performed specifically for the chemoprevention of UVB-induced skin cancer. Ultra-flexible nanocarriers, transethosomes nanocarriers, silica nanoparticles, silver nanoparticles, nanocapsule suspensions, microemulsion, nanoemulsion, and polymeric nanoparticles which have been used so far to deliver the desired drug molecule for preventing the UVB-induced skin cancer. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Induction of Skin-Derived Precursor Cells from Human Induced Pluripotent Stem Cells.

Science.gov (United States)

Sugiyama-Nakagiri, Yoriko; Fujimura, Tsutomu; Moriwaki, Shigeru

2016-01-01

The generation of full thickness human skin from dissociated cells is an attractive approach not only for treating skin diseases, but also for treating many systemic disorders. However, it is currently not possible to obtain an unlimited number of skin dermal cells. The goal of this study was to develop a procedure to produce skin dermal stem cells from induced pluripotent stem cells (iPSCs). Skin-derived precursor cells (SKPs) were isolated as adult dermal precursors that could differentiate into both neural and mesodermal progenies and could reconstitute the dermis. Thus, we attempted to generate SKPs from iPSCs that could reconstitute the skin dermis. Human iPSCs were initially cultured with recombinant noggin and SB431542, an inhibitor of activin/nodal and TGFβ signaling, to induce neural crest progenitor cells. Those cells were then treated with SKP medium that included CHIR99021, a WNT signal activator. The induction efficacy from neural crest progenitor cells to SKPs was more than 97%. No other modifiers tested were able to induce those cells. Those human iPSC-derived SKPs (hiPSC-SKPs) showed a similar gene expression signature to SKPs isolated from human skin dermis. Human iPSC-SKPs differentiated into neural and mesodermal progenies, including adipocytes, skeletogenic cell types and Schwann cells. Moreover, they could be induced to follicular type keratinization when co-cultured with human epidermal keratinocytes. We here provide a new efficient protocol to create human skin dermal stem cells from hiPSCs that could contribute to the treatment of various skin disorders.

Topical application of ST266 reduces UV-induced skin damage

Directory of Open Access Journals (Sweden)

Guan L

2017-11-01

Full Text Available Linna Guan,1 Amanda Suggs,1 Emily Galan,1 Minh Lam,1 Elma D Baron1,2 1Department of Dermatology, Case Western Reserve University, 2Cleveland Veterans Affairs Medical Center, Cleveland, OH, USA Abstract: Ultraviolet radiation (UVR has a significant impact on human skin and is the major environmental factor for skin cancer formation. It is also believed that 80% of the signs of skin aging are attributed to UVR. UVR induces inflammatory changes in the skin via the increase in oxidative stress, DNA damage vascular permeability, and fluctuation in a myriad of cytokines. Acutely, UVR causes skin inflammation and DNA damage, which manifest as sunburn (erythema. ST266 is the secretome of proprietary amnion-derived cells that have been shown to reduce inflammation and accelerate healing of various wounds by promoting migration of keratinocytes and fibroblasts in preclinical animal studies. We hypothesized that ST266 has anti-inflammatory effects that can be used to reduce ultraviolet (UV erythema and markers of inflammation. In this study, we examined the in vivo effects of ST266 on post UV-irradiated skin by measuring erythema, level of cyclobutane pyrimidine dimer (CPD, and expression level of xeroderma pigmentosum, complementation group A (XPA. We demonstrated that ST266 has the potential to reduce the acute effects of UV-induced skin damage when applied immediately after the initial exposure. In addition, ST266 is shown to reduce erythema, increase XPA DNA repair protein, and decrease damaged DNA. Keywords: ST266, photoaging, erythema, CPD, XPA, UV-induced DNA damage

A study of the effects of physical dermabrasion combined with chemical peeling in porcine skin.

Science.gov (United States)

Kang, Boo Kyoung; Choi, Jeong Hwee; Jeong, Ki Heon; Park, Jong Min; Suh, Dong Hye; Lee, Sang Jun; Shin, Min Kyung

2015-02-01

Many comparative studies of chemical peeling and dermabrasion have been reported. However, rare basic scientific data about the immediate effects after combined treatment with chemical peeling and dermabrasion have been confirmed. The aim of this study is to evaluate the effect of the application of physical abrasion in combination with chemical peels. Three pigs were treated with physical abrasion using a water jet device in combination with an α-hydroxy acid solution, and the skin samples of the control received chemical peeling solution alone. The levels of growth factors and neuropeptides were measured with a multiplex immunoassay. Skin treated with physical dermabrasion combined with chemical peeling showed prominent detachment and swelling of the stratum corneum (SC), and fluid collection in the hair follicles. The mean cell count of CD34 positive fibroblasts and mast cells, levels of epidermal growth factor, fibroblast growth factor-2, vascular endothelial growth factor, and neurotensin, were significantly increased in the tissue treated with physical abrasion combined with a chemical peeling agent, compared to the skin in the control. We concluded that physical dermabrasion combined with chemical peeling can be more effective than chemical peeling alone, for the approach through transfollicular routes.

An in vitro human skin test for assessing sensitization potential.

Science.gov (United States)

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

2016-05-01

Sensitization to chemicals resulting in an allergy is an important health issue. The current gold-standard method for identification and characterization of skin-sensitizing chemicals was the mouse local lymph node assay (LLNA). However, for a number of reasons there has been an increasing imperative to develop alternative approaches to hazard identification that do not require the use of animals. Here we describe a human in-vitro skin explant test for identification of sensitization hazards and the assessment of relative skin sensitizing potency. This method measures histological damage in human skin as a readout of the immune response induced by the test material. Using this approach we have measured responses to 44 chemicals including skin sensitizers, pre/pro-haptens, respiratory sensitizers, non-sensitizing chemicals (including skin-irritants) and previously misclassified compounds. Based on comparisons with the LLNA, the skin explant test gave 95% specificity, 95% sensitivity, 95% concordance with a correlation coefficient of 0.9. The same specificity and sensitivity were achieved for comparison of results with published human sensitization data with a correlation coefficient of 0.91. The test also successfully identified nickel sulphate as a human skin sensitizer, which was misclassified as negative in the LLNA. In addition, sensitizers and non-sensitizers identified as positive or negative by the skin explant test have induced high/low T cell proliferation and IFNγ production, respectively. Collectively, the data suggests the human in-vitro skin explant test could provide the basis for a novel approach for characterization of the sensitizing activity as a first step in the risk assessment process. Copyright © 2015 John Wiley & Sons, Ltd.

The Clinical Test of Nano gold Cosmetic for Recovering Skin Damage Due to Chemicals: Special Case

Science.gov (United States)

Taufikurohmah, T.; Wardana, A. P.; Tjahjani, S.; Sanjaya, I. G. M.; Baktir, A.; Syahrani, A.

2018-01-01

Manufacturing of Nano gold cosmetics was done at PT. Gizi Indonesia. Clinical trials to cosmetics data supported that cosmetics are able to treat skin health which has been reported partially. For special cases, the recovery process of facial skin damage should also receive attention including cases of facial skin damage caused by chemicals such as phenol, HCl, aqua regia or other harsh chemicals. The problem determined whether the Nano gold is able to recover skin damage due to the harsh chemicals. This clinical trial data on the forms of early skin damage caused by phenol was delivered in the forms of facial photos patients. The recovery progress of facial skin condition was obtained every week for two months. The data included the forms of widespread wounds during the recovery process. This statement supported by anova statistical analysis of the widespread wound changing every week for 8 times. The conclusion is skin damage due to Phenol impregnation can be recovered with the use of Nano gold cosmetics for 8 weeks. This results support the manufacturing of Nano gold cosmetics for the needs of society. It also suggest that Nano gold material can be used for medicine manufacturing in the future.

Surfactant-induced skin irritation and skin repair. Evaluation of the acute human irritation model by noninvasive techniques.

Science.gov (United States)

Wilhelm, K P; Freitag, G; Wolff, H H

1994-06-01

Although the induction of irritant dermatitis by surfactants has been extensively studied in recent years, our understanding of the repair phase of irritant dermatitis is limited. We investigated qualitative and quantitative differences in surfactant-induced irritant skin reactions from short-term exposure to three structurally different surfactants. Sodium lauryl sulfate (SLS), dodecyl trimethyl ammonium bromide (DTAB), and potassium soap were the model irritants. Surfactant solutions (0.5%) were applied for 24 hours to the volar aspect of the forearm of 11 volunteers. Irritant reactions were assessed until complete healing was indicated by visual assessment and by various aspects of skin function, that is, transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum that is, transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum corneum hydration (electrical capacitance). SLS and DTAB induced similar degrees of erythema, whereas SLS induced significantly higher TEWL increase. Although both erythema and TEWL were highest 1 hour after exposure to surfactants, skin dryness was a symptom with delayed onset, justifying the long observation period in this study. Minimum hydration values were measured as late as 7 days after surfactant exposure. Dryness was significantly more pronounced in areas exposed to SLS than in areas exposed to DTAB. Complete repair of the irritant reaction induced by either SLS or DTAB was achieved 17 days after surfactant exposure. Stratum corneum hydration was the last feature to return to baseline values. Potassium soap did not significantly influence any skin function. We emphasize the importance of extended periods needed before a patient with irritant contact dermatitis can be reexposed to irritant substances. The evaluation of the irritation potential of diverse surfactants depended significantly on the feature (erythema vs hydration and TEWL) measured.

CON4EI: SkinEthic™ Human Corneal Epithelium Eye Irritation Test (SkinEthic™ HCE EIT) for hazard identification and labelling of eye irritating chemicals.

Science.gov (United States)

Van Rompay, A R; Alépée, N; Nardelli, L; Hollanders, K; Leblanc, V; Drzewiecka, A; Gruszka, K; Guest, R; Kandarova, H; Willoughby, J A; Verstraelen, S; Adriaens, E

2018-06-01

Assessment of ocular irritancy is an international regulatory requirement and a necessary step in the safety evaluation of industrial and consumer products. Although a number of in vitro ocular irritation assays exist, none are capable of fully categorizing chemicals as a stand-alone assay. Therefore, the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was developed with the goal of assessing the reliability of eight in vitro/alternative test methods as well as establishing an optimal tiered-testing strategy. One of the in vitro assays selected was the validated SkinEthic™ Human Corneal Epithelium Eye Irritation Test method (SkinEthic™ HCE EIT). The SkinEthic™ HCE EIT has already demonstrated its capacity to correctly identify chemicals (both substances and mixtures) not requiring classification and labelling for eye irritation or serious eye damage (No Category). The goal of this study was to evaluate the performance of the SkinEthic™ HCE EIT test method in terms of the important in vivo drivers of classification. For the performance with respect to the drivers all in vivo Cat 1 and No Cat chemicals were 100% correctly identified. For Cat 2 chemicals the liquids and the solids had a sensitivity of 100% and 85.7%, respectively. For the SkinEthic™ HCE EIT test method, 100% concordance in predictions (No Cat versus No prediction can be made) between the two participating laboratories was obtained. The accuracy of the SkinEthic™ HCE EIT was 97.5% with 100% sensitivity and 96.9% specificity. The SkinEthic™ HCE EIT confirms its excellent results of the validation studies. Copyright © 2017. Published by Elsevier Ltd.

Resveratrol-Enriched Rice Attenuates UVB-ROS-Induced Skin Aging via Downregulation of Inflammatory Cascades

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Lalita Subedi

2017-01-01

Full Text Available The skin is the outermost protective barrier between the internal and external environments in humans. Chronic exposure to ultraviolet (UV radiation is a major cause of skin aging. UVB radiation penetrates the skin and induces ROS production that activates three major skin aging cascades: matrix metalloproteinase- (MMP- 1-mediated aging; MAPK-AP-1/NF-κB-TNF-α/IL-6, iNOS, and COX-2-mediated inflammation-induced aging; and p53-Bax-cleaved caspase-3-cytochrome C-mediated apoptosis-induced aging. These mechanisms are collectively responsible for the wrinkling and photoaging characteristic of UVB-induced skin aging. There is an urgent requirement for a treatment that not only controls these pathways to prevent skin aging but also avoids the adverse effects often encountered when applying bioactive compounds in concentrated doses. In this study, we investigated the efficacy of genetically modified normal edible rice (NR that produces the antiaging compound resveratrol (R as a treatment for skin aging. This resveratrol-enriched rice (RR overcomes the drawbacks of R and enhances its antiaging potential by controlling the abovementioned three major pathways of skin aging. RR does not exhibit the toxicity of R alone and promisingly downregulates the pathways underlying UVB-ROS-induced skin aging. These findings advocate the use of RR as a nutraceutical for antiaging purposes.

The Skin Microbiome: Is It Affected by UV-induced Immune Suppression?

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Patra, VijayKumar; Byrne, Scott N.; Wolf, Peter

2016-01-01

Human skin apart from functioning as a physical barricade to stop the entry of pathogens, also hosts innumerable commensal organisms. The skin cells and the immune system constantly interact with microbes, to maintain cutaneous homeostasis, despite the challenges offered by various environmental factors. A major environmental factor affecting the skin is ultraviolet radiation (UV-R) from sunlight. UV-R is well known to modulate the immune system, which can be both beneficial and deleterious. By targeting the cells and molecules within skin, UV-R can trigger the production and release of antimicrobial peptides, affect the innate immune system and ultimately suppress the adaptive cellular immune response. This can contribute to skin carcinogenesis and the promotion of infectious agents such as herpes simplex virus and possibly others. On the other hand, a UV-established immunosuppressive environment may protect against the induction of immunologically mediated skin diseases including some of photodermatoses such as polymorphic light eruption. In this article, we share our perspective about the possibility that UV-induced immune suppression may alter the landscape of the skin’s microbiome and its components. Alternatively, or in concert with this, direct UV-induced DNA and membrane damage to the microbiome may result in pathogen associated molecular patterns (PAMPs) that interfere with UV-induced immune suppression. PMID:27559331

Radiation-induced skin cancer and radiodermatitis of the head and neck

International Nuclear Information System (INIS)

van Vloten, W.A.; Hermans, J.; van Daal, W.A.

1987-01-01

From a cohort of 2400 patients who had been irradiated 19 to 48 years previously for benign diseases in the head and neck region a randomly selected group of 605 patients was selected and traced back. From the 360 patients alive, 257 were examined clinically and 49 were examined by questionnaire for radiation-induced skin tumors and radiodermatitis. In 21 patients, a total of 30 skin tumors were diagnosed. In 8 of 21 patients, 10 skin carcinomas were detected at recall. A dose-effect relationship of 40 carcinomas/10(4) persons/Gy for a median follow-up period of 41 years for the area exposed was calculated. The severity of radiodermatitis is associated with a higher prevalence of skin cancer. The number of radiation-induced skin cancers rises with the post-treatment time. Because of these late radiation effects, radiotherapy of benign skin lesions is contraindicated, especially now that other therapy modalities are available

Retinoic Acid-Induced Epidermal Transdifferentiation in Skin

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Yoshihiro Akimoto

2014-06-01

Full Text Available Retinoids function as important regulatory signaling molecules during development, acting in cellular growth and differentiation both during embryogenesis and in the adult animal. In 1953, Fell and Mellanby first found that excess vitamin A can induce transdifferentiation of chick embryonic epidermis to a mucous epithelium (Fell, H.B.; Mellanby, E. Metaplasia produced in cultures of chick ectoderm by high vitamin A. J. Physiol. 1953, 119, 470–488. However, the molecular mechanism of this transdifferentiation process was unknown for a long time. Recent studies demonstrated that Gbx1, a divergent homeobox gene, is one of the target genes of all-trans retinoic acid (ATRA for this transdifferentiation. Furthermore, it was found that ATRA can induce the epidermal transdifferentiation into a mucosal epithelium in mammalian embryonic skin, as well as in chick embryonic skin. In the mammalian embryonic skin, the co-expression of Tgm2 and Gbx1 in the epidermis and an increase in TGF-β2 expression elicited by ATRA in the dermis are required for the mucosal transdifferentiation, which occurs through epithelial-mesenchymal interaction. Not only does retinoic acid (RA play an important role in mucosal transdifferentiation, periderm desquamation, and barrier formation in the developing mammalian skin, but it is also involved in hair follicle downgrowth and bending by its effect on the Wnt/β-catenin pathway and on members of the Runx, Fox, and Sox transcription factor families.

Chemically dispersed oil is cytotoxic and genotoxic to sperm whale skin cells.

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Wise, Catherine F; Wise, James T F; Wise, Sandra S; Wise, John Pierce

2018-06-01

Two major oil crises in United States history, the 1989 Exxon-Valdez oil spill in Alaska and the 2010 Deepwater Horizon Oil Rig explosion in the Gulf of Mexico, drew attention to the need for toxicological experiments on oil and chemically dispersed oil. We are still learning the effects these spills had on wildlife. However, little data is known about the toxicity of these substances in marine mammals. The objective of this study is to determine the toxicity of Alaskan oil, as well as chemically dispersed oil. Oil experiments were performed using the water accommodated fraction of Alaskan oil (WAF) and the chemically enhanced water accommodated fraction of Alaskan oil (CEWAF). The Alaskan WAF is not cytotoxic to sperm whale skin cells though it did induce chromosome damage; S9-mediated metabolism did not affect the cytotoxicity of WAF but did increase the levels of chromosome damage. Alaskan CEWAF is more cytotoxic and genotoxic than the WAF; S9 mediated metabolism increased both cytotoxicity and genotoxicity of CEWAF. Analysis of the PAH content of Alaskan WAF and CEWAF revealed a forty-fold increase in the total levels of PAHs in CEWAF compared to WAF. These findings show that chemically dispersed oil leads to higher levels of PAH exposure which are more toxic and likely to lead to longer and more persistent health effects. Copyright © 2017 Elsevier Inc. All rights reserved.

A case of radiation-induced skin cancer of the neck

International Nuclear Information System (INIS)

Matsushita, Tetsuya; Susuki, Takeo; Kikui, Tomoko; Masada, Yoshiko; Tahara, Shinya.

1994-01-01

The authors discuss the case of radiation-induced skin cancer of the neck in a 76-year-old woman who had undergone irradiation of tubercular lymphadenitis of the cervix while in her low teens. Some fifty years later, a squamous cell carcinoma developed in the irradiated region and in due course deeply invaded the sternocleidomastoidous muscle. Thus, a radical neck dissection was performed and the tumor and the lymph tissue removed en bloc, after which reconstruction was accomplished by using a latissimus dorsi musculocutaneous flap. With regard to the lessons learned from treating this case, three points are considered important and are listed below. When treating radiation-induced skin cancer patients, the head and neck regions should be examined in detail for the presence of other tumors. The excision of the skin surrounding the tumor should be as wide as possible, so as to remove skin that may have been also over-subjected to irradiation. The remaining skin surrounding the defect left by the excision is atrophic and thin. (author)

Photobiological implications of melanin photoprotection after UVB-induced tanning of human skin but not UVA-induced tanning.

Science.gov (United States)

Coelho, Sergio G; Yin, Lanlan; Smuda, Christoph; Mahns, Andre; Kolbe, Ludger; Hearing, Vincent J

2015-03-01

Repetitive suberythemal UVA and/or UVB exposures were used to generate comparable UV-induced tans in human skin over the course of 2 weeks. To evaluate the potential photoprotective values of those UVA- and/or UVB- induced tans and to avoid the confounding issue of residual UV-induced DNA damage, we waited 1 week before challenging those areas with a 1.5 MED of UVA+UVB after which we measure DNA damage. The results show that the type of UV used to induce skin pigmentation affects the redistribution of melanin in the skin and/or de novo melanin synthesis. The UVA-induced tans failed to even provide a minimal SPF of 1.5, which suggests that producing a tan with UVA-rich sunlamps prior to a holiday or vacation is completely counterproductive. Published 2014. This article is a US Government work and is in the public domain in the USA.

Numerical simulation study on rolling-chemical milling process of aluminum-lithium alloy skin panel

Science.gov (United States)

Huang, Z. B.; Sun, Z. G.; Sun, X. F.; Li, X. Q.

2017-09-01

Single curvature parts such as aircraft fuselage skin panels are usually manufactured by rolling-chemical milling process, which is usually faced with the problem of geometric accuracy caused by springback. In most cases, the methods of manual adjustment and multiple roll bending are used to control or eliminate the springback. However, these methods can cause the increase of product cost and cycle, and lead to material performance degradation. Therefore, it is of significance to precisely control the springback of rolling-chemical milling process. In this paper, using the method of experiment and numerical simulation on rolling-chemical milling process, the simulation model for rolling-chemical milling process of 2060-T8 aluminum-lithium alloy skin was established and testified by the comparison between numerical simulation and experiment results for the validity. Then, based on the numerical simulation model, the relative technological parameters which influence on the curvature of the skin panel were analyzed. Finally, the prediction of springback and the compensation can be realized by controlling the process parameters.

Melatonin Role in Ameliorating Radiation-induced Skin Damage: From Theory to Practice (A Review of Literature

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Abbaszadeh A.

2017-06-01

Full Text Available Normal skin is composed of epidermis and dermis. Skin is susceptible to radiation damage because it is a continuously renewing organ containing rapidly proliferating mature cells. Radiation burn is a damage to the skin or other biological tissues caused by exposure to radiofrequency energy or ionizing radiation. Acute skin reaction is the most frequently occurring side effect of radiation therapy. Generally, any chemical/ biological agent given before or at the time of irradiation to prevent or ameliorate damage to normal tissues is called a radioprotector. Melatonin is a highly lipophilic substance that easily penetrates organic membranes and therefore is able to protect important intracellular structures including mitochondria and DNA against oxidative damage directly at the sites where such a kind of damage would occur. Melatonin leads to an increase in the molecular level of some important antioxidative enzymes such as superoxide, dismotase and glutation-peroxidase, and also a reduction in synthetic activity of nitric oxide. There is a large body of evidence which proves the efficacy of Melatonin in ameliorating UV and X ray-induced skin damage. We propose that, in the future, Melatonin would improve the therapeutic ratio in radiation oncology and ameliorate skin damage more effectively when administered in optimal and non-toxic doses

Predicting skin permeability from complex chemical mixtures

International Nuclear Information System (INIS)

Riviere, Jim E.; Brooks, James D.

2005-01-01

Occupational and environmental exposure to topical chemicals is usually in the form of complex chemical mixtures, yet risk assessment is based on experimentally derived data from individual chemical exposures from a single, usually aqueous vehicle, or from computed physiochemical properties. We present an approach using hybrid quantitative structure permeation relationships (QSPeR) models where absorption through porcine skin flow-through diffusion cells is well predicted using a QSPeR model describing the individual penetrants, coupled with a mixture factor (MF) that accounts for physicochemical properties of the vehicle/mixture components. The baseline equation is log k p = c + mMF + aΣα 2 H + bΣβ 2 H + sπ 2 H + rR 2 + vV x where Σα 2 H is the hydrogen-bond donor acidity, Σβ 2 H is the hydrogen-bond acceptor basicity, π 2 H is the dipolarity/polarizability, R 2 represents the excess molar refractivity, and V x is the McGowan volume of the penetrants of interest; c, m, a, b, s, r, and v are strength coefficients coupling these descriptors to skin permeability (k p ) of 12 penetrants (atrazine, chlorpyrifos, ethylparathion, fenthion, methylparathion, nonylphenol, ρ-nitrophenol, pentachlorophenol, phenol, propazine, simazine, and triazine) in 24 mixtures. Mixtures consisted of full factorial combinations of vehicles (water, ethanol, propylene glycol) and additives (sodium lauryl sulfate, methyl nicotinate). An additional set of 4 penetrants (DEET, SDS, permethrin, ricinoleic acid) in different mixtures were included to assess applicability of this approach. This resulted in a dataset of 16 compounds administered in 344 treatment combinations. Across all exposures with no MF, R 2 for absorption was 0.62. With the MF, correlations increased up to 0.78. Parameters correlated to the MF include refractive index, polarizability and log (1/Henry's Law Constant) of the mixture components. These factors should not be considered final as the focus of these studies

Radiation-induced malignant tumors of skin and their histogenesis

International Nuclear Information System (INIS)

Li Guomin; Chen Yunchi; Yang Yejing

1987-01-01

Seven cases of radiation-induced malignant tumors and 60 cases of chronic radiation damage of skin are reported. Severe hyperplasia, false epitheliomatoid hyperpiasia and atypical proliferation of epithelia and atypical proliferation of fibrohistocytes were the main changes found in chronic radiation damage of skin. The development of malignant tumors from chronic radiation damage of skin can be divided into 4 periods: necrotic and degenerative change period, benign proliferative period, atypical proliferative period and malignant change period. The incidence of hyperplastic changes of skin is related to the time elapse after irradiation and the integrated dose of radiation. The longer the duration after irradiation and the larger the integrated dose are, the higher will be the incidence of hyperplastic changes

A simple in chemico method for testing skin sensitizing potential of chemicals using small endogenous molecules.

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Nepal, Mahesh Raj; Shakya, Rajina; Kang, Mi Jeong; Jeong, Tae Cheon

2018-06-01

Among many of the validated methods for testing skin sensitization, direct peptide reactivity assay (DPRA) employs no cells or animals. Although no immune cells are involved in this assay, it reliably predicts the skin sensitization potential of a chemical in chemico. Herein, a new method was developed using endogenous small-molecular-weight compounds, cysteamine and glutathione, rather than synthetic peptides, to differentiate skin sensitizers from non-sensitizers with an accuracy as high as DPRA. The percent depletion of cysteamine and glutathione by test chemicals was measured by an HPLC equipped with a PDA detector. To detect small-size molecules, such as cysteamine and glutathione, a derivatization by 4-(4-dimethylaminophenylazo) benzenesulfonyl chloride (DABS-Cl) was employed prior to the HPLC analysis. Following test method optimization, a cut-off criterion of 7.14% depletion was applied to differentiate skin sensitizers from non-sensitizers in combination of the ratio of 1:25 for cysteamine:test chemical with 1:50 for glutathione:test chemical for the best predictivity among various single or combination conditions. Although overlapping HPLC peaks could not be fully resolved for some test chemicals, high levels of sensitivity (100.0%), specificity (81.8%), and accuracy (93.3%) were obtained for 30 chemicals tested, which were comparable or better than those achieved with DPRA. Copyright © 2018 Elsevier B.V. All rights reserved.

Cadmium-induced disruption of environmental exploration and chemical communication in matrinxa, Brycon amazonicus

International Nuclear Information System (INIS)

Honda, R.T.; Fernandes-de-Castilho, M.; Val, A.L.

2008-01-01

The effects of cadmium exposure on both environment exploration and behavioral responses induced by alarm substance in matrinxa (Brycon amazonicus), a fish species endemic to the Amazon basin, were investigated. Fish exposed to 9.04 ± 0.07 μg/L waterborne cadmium for 96 h followed by 24 h depuration period in clean water, were video-recorded for 15 min, followed by immediate introduction of conspecific skin extract to the tank and a new 30 min period of fish video-recording. Cd-exposed matrinxa showed a significantly lowered locomotor activity (t-test t 12 = 2.7; p = 0.025) and spatial distribution (t-test t 12 = 2.4; p = 0.03) relative to the unexposed control fish prior to the alarm substance introduction, and did not present any significant reaction when the skin extract was introduced. The control fish, in opposite, showed a higher level of activity and spatial distribution prior the skin extract contact and significantly decreased their response after the chemical stimulus (locomotion-repeated-measure ANOVA F 1,11 = 5.6; p = 0.04; spatial distribution F 1,11 = 19.4; p = 0.001). In conclusion, exposure to a low level of cadmium affects both the environment exploration performance and the conspecific chemical communication in matrinxa. If the reduced environmental exploration performance of Cd-exposed fish is an adjustment to the compromised chemical communication or an independent effect of cadmium is the next step to be investigated

Cadmium-induced disruption of environmental exploration and chemical communication in matrinxa, Brycon amazonicus

Energy Technology Data Exchange (ETDEWEB)

Honda, R.T. [Centro Universitario Nilton Lins - CUNL, Laboratory of Toxicology, Av. Prof. Nilton Lins 3259, Parque das Laranjeiras, Zip 69058-040 Manaus, AM (Brazil)], E-mail: rhonda@niltonlins.br; Fernandes-de-Castilho, M. [Universidade Federal do Parana - UFPR, Research Center on Animal Welfare (RECAW), Laboratory of Studies on Animal Stress, Department of Physiology, Sector of Biological Science, Jardim das Americas, Zip 81531-970 Curitiba, PR (Brazil); Val, A.L. [Instituto Nacional de Pesquisas da Amazonia - INPA, Laboratory of Ecophysiology and Molecular Evolution, Av. Andre Araujo 2936, Aleixo, Zip 69083-000 Manaus, AM (Brazil)

2008-09-17

The effects of cadmium exposure on both environment exploration and behavioral responses induced by alarm substance in matrinxa (Brycon amazonicus), a fish species endemic to the Amazon basin, were investigated. Fish exposed to 9.04 {+-} 0.07 {mu}g/L waterborne cadmium for 96 h followed by 24 h depuration period in clean water, were video-recorded for 15 min, followed by immediate introduction of conspecific skin extract to the tank and a new 30 min period of fish video-recording. Cd-exposed matrinxa showed a significantly lowered locomotor activity (t-test t{sub 12} = 2.7; p = 0.025) and spatial distribution (t-test t{sub 12} = 2.4; p = 0.03) relative to the unexposed control fish prior to the alarm substance introduction, and did not present any significant reaction when the skin extract was introduced. The control fish, in opposite, showed a higher level of activity and spatial distribution prior the skin extract contact and significantly decreased their response after the chemical stimulus (locomotion-repeated-measure ANOVA F{sub 1,11} = 5.6; p = 0.04; spatial distribution F{sub 1,11} = 19.4; p = 0.001). In conclusion, exposure to a low level of cadmium affects both the environment exploration performance and the conspecific chemical communication in matrinxa. If the reduced environmental exploration performance of Cd-exposed fish is an adjustment to the compromised chemical communication or an independent effect of cadmium is the next step to be investigated.

Radiation-induced skin carcinomas of the head and neck

International Nuclear Information System (INIS)

Ron, E.; Modan, B.; Preston, D.; Alfandary, E.; Stovall, M.; Boice, J.D. Jr.

1991-01-01

Radiation exposures to the scalp during childhood for tinea capitis were associated with a fourfold increase in skin cancer, primarily basal cell carcinomas, and a threefold increase in benign skin tumors. Malignant melanoma, however, was not significantly elevated. Overall, 80 neoplasms were identified from an extensive search of the pathology logs of all major hospitals in Israel and computer linkage with the national cancer registry. Radiation dose to the scalp was computed for over 10,000 persons irradiated for ringworm (mean 7 Gy), and incidence rates were contrasted with those observed in 16,000 matched comparison subjects. The relative risk of radiogenic skin cancer did not differ significantly between men or women or by time since exposure; however, risk was greatest following exposures in early childhood. After adjusting for sex, ethnic origin, and attained age, the estimated excess relative risk was 0.7 per Gy and the average excess risk over the current follow-up was 0.31/10(4) PY-Gy. The risk per Gy of radiation-induced skin cancer was intermediate between the high risk found among whites and no risk found among blacks in a similar study conducted in New York City. This finding suggests the role that subsequent exposure to uv radiation likely plays in the expression of a potential radiation-induced skin malignancy

Chemical profiling and cytotoxicity assay of bufadienolides in toad venom and toad skin.

Science.gov (United States)

Meng, Qiong; Yau, Lee-Fong; Lu, Jing-Guang; Wu, Zhen-Zhen; Zhang, Bao-Xian; Wang, Jing-Rong; Jiang, Zhi-Hong

2016-07-01

Toad venom and toad skin have been widely used for treating various cancers in China. Bufadienolides are regarded as the main anticancer components of toad venom, but the difference on composition and anticancer activities of bufadienolides between toad venom and toad skin remains unclear. Fractions enriched with free and conjugated bufadienolides were prepared from toad venom and toad skin. Bufadienolides in each fraction were comprehensively profiled by using a versatile UHPLC-TOF-MS method. Relative contents of major bufadienolides were determined by using three bufogenins and one bufotoxin as marker compounds with validated UHPLC-TOF-MS method. Furthermore, cytotoxicity of the fractions was examined by MTT assay. Two fractions, i.e., bufogenin and bufotoxin fractions (TV-F and TV-C) were isolated from toad venom, and one bufotoxin fraction (TS-C) was isolated from toad skin. Totally 56 bufadienolides in these three fractions were identified, and 29 were quantified or semi-quantified. Bufotoxins were identified in both toad venom and toad skin, whereas bufogenins exist only in toad venom. Bufalin-3-conjugated bufotoxins are major components in toad venom, whereas cinobufotalin and cinobufagin-3-conjugated bufotoxins are main bufotoxins in toad skin. MTT assay revealed potent cytotoxicity of all the fractions in an order of TV-F>TV-C>TS-C. Our study represents the most comprehensive investigation on the chemical profiles of toad venom and toad skin from both qualitative and quantitative aspects. Eight bufotoxins were identified in toad skin responsible for the cytotoxicity for the first time. Our research provides valuable chemical evidence for the appropriate processing method, quality control and rational exploration of toad skin and toad venom for the development of anticancer medicines. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Quantification of gravity-induced skin strain across the breast surface.

Science.gov (United States)

Sanchez, Amy; Mills, Chris; Haake, Steve; Norris, Michelle; Scurr, Joanna

2017-12-01

Quantification of the magnitude of skin strain in different regions of the breast may help to estimate possible gravity-induced damage whilst also being able to inform the selection of incision locations during breast surgery. The aim of this study was to quantify static skin strain over the breast surface and to estimate the risk of skin damage caused by gravitational loading. Fourteen participants had 21 markers applied to their torso and left breast. The non-gravity breast position was estimated as the mid-point of the breast positions in water and soybean oil (higher and lower density than breast respectively). The static gravity-loaded breast position was also measured. Skin strain was calculated as the percentage extension between adjacent breast markers in the gravity and non-gravity loaded conditions. Gravity induced breast deformation caused peak strains ranging from 14 to 75% across participants, with potentially damaging skin strain (>60%) in one participant and skin strains above 30% (skin resistance zone) in a further four participants. These peak strain values all occurred in the longitudinal direction in the upper region of the breast skin. In the latitudinal direction, smaller-breasted participants experienced greater strain on the outer (lateral) breast regions and less strain on the inner (medial) breast regions, a trend which was reversed in the larger breasted participants (above size 34D). To reduce tension on surgical incisions it is suggested that preference should be given to medial latitudinal locations for smaller breasted women and lateral latitudinal locations for larger breasted women. Copyright © 2017 Elsevier Ltd. All rights reserved.

Poly(I:C) induces expressions of MMP-1, -2, and -3 through various signaling pathways including IRF3 in human skin fibroblasts.

Science.gov (United States)

Yao, Cheng; Lee, Dong Hun; Oh, Jang-Hee; Kim, Min-Kyoung; Kim, Kyu Han; Park, Chi-Hyun; Chung, Jin Ho

2015-10-01

Ultraviolet (UV) irradiation can result in premature skin aging (photoaging) which is characterized by decreased expression of collagen and increased expression of matrix metalloproteinases (MMPs). Double-stranded RNAs (dsRNAs) can be generated at various conditions including virally infected cells or UV-damaged skin cells. Recent studies have shown that a synthetic dsRNA, polyinosinic-polycytidylic acid (poly(I:C)), can reduce procollagen expression in human skin fibroblasts. However, little is known about the effect of poly(I:C) on the expression of MMPs in skin fibroblasts and its underlying mechanisms. We examined the effect of poly(I:C) on MMP-1, -2, and -3 expressions in human skin fibroblasts. Then, we further explored the underlying signaling pathways involved in the processes. Human skin fibroblasts were treated with poly(I:C) for the indicated times in the presence or the absence of various chemical inhibitors or small interfering RNAs (siRNAs) at the indicated concentrations. Protein and mRNA levels of various target molecules were examined by Western blotting and quantitative real-time PCR, respectively. Poly(I:C) induced MMP-1, -2, and -3 expressions, which were dependent on TLR3. Poly(I:C) also induced activations of the mitogen-activated protein kinases (MAPKs), the nuclear factor-kappaB (NF-κB) and the interferon regulatory factor 3 (IRF3) pathways. By using specific inhibitors, we found that poly(I:C)-induced expressions of MMP-1, -2, and -3 were differentially regulated by these signaling pathways. In particular, we found that the inhibition of IRF3 signaling pathways attenuated poly(I:C)-induced expressions of all the three MMPs. Our data show that the expressions of MMP-1, -2, and -3 are induced by poly(I:C) through various signaling pathways in human skin fibroblasts and suggest that TLR3 and/or IRF3 may be good targets for regulating the expressions of MMP-1, -2, and -3 induced by dsRNAs. Copyright © 2015 Elsevier Ireland Ltd. All rights

The role of natural and UV-induced skin pigmentation on low-fluence IPL-induced side effects: a randomized controlled trial.

Science.gov (United States)

Thaysen-Petersen, Daniel; Lin, Jennifer Y; Nash, Jf; Beerwerth, Frank; Wulf, Hans C; Philipsen, Peter A; Haedersdal, Merete

2014-02-01

The risk of adverse skin effects following light-based hair removal is greater in pigmented skin based on the theory of selective photothermolysis. Thus sunlight-induced pigment i.e., facultative pigmentation, increases the risk of adverse skin effects, perhaps disproportionately. The aim of this study was to evaluate the influence of constitutive and facultative skin pigmentation on low-fluence intense pulsed light (IPL)-induced adverse skin effects. Twenty-one subjects with Fitzpatrick skin type II-IV were enrolled. Two buttock blocks were randomized to receive 0 or 8 solar simulated ultraviolet radiation (UVR) exposures of consecutively increasing Standard Erythema Doses (2-4 SED). Each block was subdivided into four sites, randomized to receive IPL of 0, 7, 8, or 10 J/cm(2) , once a week for 3 weeks. Biopsies were taken 16-24 hours after the first IPL exposure and subjects were seen 1 and 4 weeks after the last IPL exposure. Outcome measures were: (i) skin reactions, (ii) pain, (iii) mRNA expression of pigment-markers microphthalmia-associated transcription factor (MITF) and pro-opiomelanocortin (POMC), and (iv) clinical appearance of biopsy wounds. Skin pigmentation increased after UVR (baseline median 13.8%, after UVR 28.1%, P = 0.0001) in all skin types. Subjects reported low pain intensities (median 1.5, scale 0-10) and experienced transient erythema immediately after IPL exposure. No persistent erythema, blisters, crusting, textual, or pigment changes were observed. The risk of erythema and pain intensities increased with IPL dose and skin pigmentation (P skin reactions in skin with similar degree of natural and facultative pigmentation (P ≥ 0.104). Expression of cellular pigment-markers was not influenced by IPL exposure, neither in constitutive nor in facultative pigmented skin. Clinical appearance of biopsy wounds was unaffected by IPL exposure. The prevalence and intensity of low-fluence IPL-induced adverse skin effects depended on IPL

Candesartan restores pressure-induced vasodilation and prevents skin pressure ulcer formation in diabetic mice.

Science.gov (United States)

Danigo, Aurore; Nasser, Mohamad; Bessaguet, Flavien; Javellaud, James; Oudart, Nicole; Achard, Jean-Michel; Demiot, Claire

2015-02-18

Angiotensin II type 1 receptor (AT1R) blockers have beneficial effects on neurovascular complications in diabetes and in organ's protection against ischemic episodes. The present study examines whether the AT1R blocker candesartan (1) has a beneficial effect on diabetes-induced alteration of pressure-induced vasodilation (PIV, a cutaneous physiological neurovascular mechanism which could delay the occurrence of tissue ischemia), and (2) could be protective against skin pressure ulcer formation. Male Swiss mice aged 5-6 weeks were randomly assigned to four experimental groups. In two groups, diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 200 mg.kg(-1)). After 6 weeks, control and STZ mice received either no treatment or candesartan (1 mg/kg-daily in drinking water) during 2 weeks. At the end of treatment (8 weeks of diabetes duration), C-fiber mediated nociception threshold, endothelium-dependent vasodilation and PIV were assessed. Pressure ulcers (PUs) were then induced by pinching the dorsal skin between two magnetic plates for three hours. Skin ulcer area development was assessed during three days, and histological examination of the depth of the skin lesion was performed at day three. After 8 weeks of diabetes, the skin neurovascular functions (C-fiber nociception, endothelium-dependent vasodilation and PIV) were markedly altered in STZ-treated mice, but were fully restored by treatment with candesartan. Whereas in diabetes mice exposure of the skin to pressure induced wide and deep necrotic lesions, treatment with candersartan restored their ability to resist to pressure-induced ulceration as efficiently as the control mice. Candesartan decreases the vulnerability to pressure-induced ulceration and restores skin neurovascular functions in mice with STZ-induced established diabetes.

Skin Rejuvenation with Non-Invasive Pulsed Electric Fields

Science.gov (United States)

Golberg, Alexander; Khan, Saiqa; Belov, Vasily; Quinn, Kyle P.; Albadawi, Hassan; Felix Broelsch, G.; Watkins, Michael T.; Georgakoudi, Irene; Papisov, Mikhail; Mihm, Martin C., Jr.; Austen, William G., Jr.; Yarmush, Martin L.

2015-05-01

Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases.

Spectrophotometer is useful for assessing vitiligo and chemical leukoderma severity by quantifying color difference with surrounding normally pigmented skin.

Science.gov (United States)

Hayashi, M; Okamura, K; Araki, Y; Suzuki, M; Tanaka, T; Abe, Y; Nakano, S; Yoshizawa, J; Hozumi, Y; Inoie, M; Suzuki, T

2018-05-01

Acquired skin hypopigmentation has many etiologies, including autoimmune melanocyte destruction, skin aging, inflammation, and chemical exposure. Distinguishing lesions from normally pigmented skin is clinically important to precisely assess disease severity. However, no gold standard assessment method has been reported. We aimed to investigate whether spectrophotometers are useful for assessing vitiligo and rhododendrol (4-(4-hydroxyphenol)-2-butanol) (Rhododenol ® )-induced leukoderma disease severity by quantifying skin color. Mexameter ® MX18 and CM-700d spectrophotometer were used for assessing vitiligo/leukoderma by measuring melanin index, L*a*b* color space, and ΔE*ab value, which represents the color difference between two subjects and is calculated by the values of L*a*b*. MX18 and CM-700d can quantitatively distinguish vitiligo/leukoderma from normally pigmented skin based on melanin index. CM-700d consistently quantified the color of vitiligo/leukoderma lesions and surrounding normally pigmented skin in L*a*b* color spaces and ΔE*ab. ΔE*ab is well correlated with melanin index and clinical appearance. ΔE*ab has been frequently used in aesthetic dentistry; however, current study is the first to use it in the measurement of skin color. ΔE*ab seems to be a useful parameter to evaluate the color contrast between vitiligo/leukoderma and surrounding normally pigmented skin and can be used to evaluate disease severity and patient's quality of life. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Infrared laser-induced chemical reactions

International Nuclear Information System (INIS)

Katayama, Mikio

1978-01-01

The experimental means which clearly distinguishes between infrared ray-induced reactions and thermal reactions has been furnished for the first time when an intense monochromatic light source has been obtained by the development of infrared laser. Consequently, infrared laser-induced chemical reactions have started to develop as one field of chemical reaction researches. Researches of laser-induced chemical reactions have become new means for the researches of chemical reactions since they were highlighted as a new promising technique for isotope separation. Specifically, since the success has been reported in 235 U separation using laser in 1974, comparison of this method with conventional separation techniques from the economic point of view has been conducted, and it was estimated by some people that the laser isotope separation is cheaper. This report briefly describes on the excitation of oscillation and reaction rate, and introduces the chemical reactions induced by CW laser and TEA CO 2 laser. Dependence of reaction yield on laser power, measurement of the absorbed quantity of infrared ray and excitation mechanism are explained. Next, isomerizing reactions are reported, and finally, isotope separation is explained. It was found that infrared laser-induced chemical reactions have the selectivity for isotopes. Since it is evident that there are many examples different from thermal and photo-chemical reactions, future collection of the data is expected. (Wakatsuki, Y.)

Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin

NARCIS (Netherlands)

Middelkamp-Hup, Maritza A.; Pathak, Madhu A.; Parrado, Concepcion; Goukassian, David; Rius-Díaz, Francisca; Mihm, Martín C.; Fitzpatrick, Thomas B.; González, Salvador

2004-01-01

BACKGROUND: UV radiation induces damage to human skin. Protection of skin by an oral photoprotective agent would have substantial benefits. Objective We investigated the photoprotective effect of oral administration of an extract of the natural antioxidant Polypodium leucotomos (PL). METHODS: A

Proteomic Profiling of Radiation-Induced Skin Fibrosis in Rats: Targeting the Ubiquitin-Proteasome System

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Wang, Wenjie [School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou (China); Cyrus Tang Hematology Center, Soochow University, Suzhou (China); Luo, Judong [Department of Radiotherapy, Changzhou Tumor Hospital, Soochow University, Changzhou (China); Sheng, Wenjiong; Xue, Jiao; Li, Ming [School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou (China); Ji, Jiang [Department of Dermatology, the Second Affiliated Hospital of Soochow University, Suzhou (China); Liu, Pengfei [Department of Gastroenterology, the Affiliated Jiangyin Hospital of Southeast University, Jiangyin (China); Zhang, Xueguang [Institute of Medical Biotechnology and Jiangsu Stem Cell Key Laboratory, Medical College of Soochow University, Suzhou (China); Cao, Jianping [School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou (China); Zhang, Shuyu, E-mail: zhang.shuyu@hotmail.com [School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou (China); Cyrus Tang Hematology Center, Soochow University, Suzhou (China)

2016-06-01

Purpose: To investigate the molecular changes underlying the pathogenesis of radiation-induced skin fibrosis. Methods and Materials: Rat skin was irradiated to 30 or 45 Gy with an electron beam. Protein expression in fibrotic rat skin and adjacent normal tissues was quantified by label-free protein quantitation. Human skin cells HaCaT and WS-1 were treated by x-ray irradiation, and the proteasome activity was determined with a fluorescent probe. The effect of proteasome inhibitors on Transforming growth factor Beta (TGF-B) signaling was measured by Western blot and immunofluorescence. The efficacy of bortezomib in wound healing of rat skin was assessed by the skin injury scale. Results: We found that irradiation induced epidermal and dermal hyperplasia in rat and human skin. One hundred ninety-six preferentially expressed and 80 unique proteins in the irradiated fibrotic skin were identified. Through bioinformatic analysis, the ubiquitin-proteasome pathway showed a significant fold change and was investigated in greater detail. In vitro experiments demonstrated that irradiation resulted in a decline in the activity of the proteasome in human skin cells. The proteasome inhibitor bortezomib suppressed profibrotic TGF-β downstream signaling but not TGF-β secretion stimulated by irradiation in HaCaT and WS-1 cells. Moreover, bortezomib ameliorated radiation-induced skin injury and attenuated epidermal hyperplasia. Conclusion: Our findings illustrate the molecular changes during radiation-induced skin fibrosis and suggest that targeting the ubiquitin-proteasome system would be an effective countermeasure.

Enoxaparin-induced skin necrosis at injection site after total knee arthroplasty

Directory of Open Access Journals (Sweden)

Max Haffner, BS

2018-03-01

Full Text Available Enoxaparin is a widely used low-molecular-weight heparin for perioperative thromboembolic prophylaxis. Enoxaparin-induced skin necrosis in the setting of arthroplasty has been rarely reported in the literature with varying outcomes and management decisions. Our patient developed skin necrosis at his injection site and thrombocytopenia 10 days following left total knee arthroplasty surgery and after receiving subcutaneous Lovenox injections postoperatively. The patient was started on an alternative anticoagulation based on a high suspicion for heparin-induced thrombocytopenia and the wound was monitored without surgical debridement. Our case highlights the key clinical management decisions when facing this potentially life-threatening adverse reaction. Keywords: Lovenox, Enoxaparin, Skin necrosis, Adverse reaction, Arthroplasty

Evaluation of a Silicone Membrane as an Alternative to Human Skin for Determining Skin Permeation Parameters of Chemical Compounds.

Science.gov (United States)

Uchida, Takashi; Yakumaru, Masafumi; Nishioka, Keisuke; Higashi, Yoshihiro; Sano, Tomohiko; Todo, Hiroaki; Sugibayashi, Kenji

2016-01-01

We evaluated the effectiveness of a silicone membrane as an alternative to human skin using the skin permeation parameters of chemical compounds. An in vitro permeation study using 15 model compounds was conducted, and permeation parameters comprising permeability coefficient (P), diffusion parameter (DL(-2)), and partition parameter (KL) were calculated from each permeation profile. Significant correlations were obtained in log P, log DL(-2), and log KL values between the silicone membrane and human skin. DL(-2) values of model compounds, except flurbiprofen, in the silicone membrane were independent of the lipophilicity of the model compounds and were 100-fold higher than those in human skin. For antipyrine and caffeine, which are hydrophilic, KL values in the silicone membrane were 100-fold lower than those in human skin, and P values, calculated as the product of a DL(-2) and KL, were similar. For lipophilic compounds, such as n-butyl paraben and flurbiprofen, KL values for silicone were similar to or 10-fold higher than those in human skin, and P values for silicone were 100-fold higher than those in human skin. Furthermore, for amphiphilic compounds with log Ko/w values from 0.5 to 3.5, KL values in the silicone membrane were 10-fold lower than those in human skin, and P values for silicone were 10-fold higher than those in human skin. The silicone membrane was useful as a human skin alternative in an in vitro skin permeation study. However, depending on the lipophilicity of the model compounds, some parameters may be over- or underestimated.

Cell-type-specific roles for COX-2 in UVB-induced skin cancer

Science.gov (United States)

Herschman, Harvey

2014-01-01

In human tumors, and in mouse models, cyclooxygenase-2 (COX-2) levels are frequently correlated with tumor development/burden. In addition to intrinsic tumor cell expression, COX-2 is often present in fibroblasts, myofibroblasts and endothelial cells of the tumor microenvironment, and in infiltrating immune cells. Intrinsic cancer cell COX-2 expression is postulated as only one of many sources for prostanoids required for tumor promotion/progression. Although both COX-2 inhibition and global Cox-2 gene deletion ameliorate ultraviolet B (UVB)-induced SKH-1 mouse skin tumorigenesis, neither manipulation can elucidate the cell type(s) in which COX-2 expression is required for tumorigenesis; both eliminate COX-2 activity in all cells. To address this question, we created Cox-2 flox/flox mice, in which the Cox-2 gene can be eliminated in a cell-type-specific fashion by targeted Cre recombinase expression. Cox-2 deletion in skin epithelial cells of SKH-1 Cox-2 flox/flox;K14Cre + mice resulted, following UVB irradiation, in reduced skin hyperplasia and increased apoptosis. Targeted epithelial cell Cox-2 deletion also resulted in reduced tumor incidence, frequency, size and proliferation rate, altered tumor cell differentiation and reduced tumor vascularization. Moreover, Cox-2 flox/flox;K14Cre + papillomas did not progress to squamous cell carcinomas. In contrast, Cox-2 deletion in SKH-1 Cox-2 flox/flox; LysMCre + myeloid cells had no effect on UVB tumor induction. We conclude that (i) intrinsic epithelial COX-2 activity plays a major role in UVB-induced skin cancer, (ii) macrophage/myeloid COX-2 plays no role in UVB-induced skin cancer and (iii) either there may be another COX-2-dependent prostanoid source(s) that drives UVB skin tumor induction or there may exist a COX-2-independent pathway(s) to UVB-induced skin cancer. PMID:24469308

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

International Nuclear Information System (INIS)

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

1997-01-01

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 → A transition) from a UV-exposed skin sample, and seven point mutations in exon 5 (codens 146, 158, 150, 165, and 161, three C → T, two C → A, one C → G, and one A → 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

Chromium-induced skin damage among Taiwanese cement workers.

Science.gov (United States)

Chou, Tzu-Chieh; Wang, Po-Chih; Wu, Jyun-De; Sheu, Shiann-Cherng

2016-10-01

Little research has been done on the relationships between chromium exposure, skin barrier function, and other hygienic habits in cement workers. Our purpose was to investigate chromium-induced skin barrier disruption due to cement exposure among cement workers. One hundred and eight cement workers were recruited in this study. Urinary chromium concentration was used to characterize exposure levels. The biological exposure index was used to separate high and low chromium exposure. Transepidermal water loss (TEWL) was used to assess the skin barrier function. TEWL was significantly increased in workers with high chromium exposure levels than those with low chromium exposure levels (p = 0.048). A positive correlation was also found between urinary chromium concentration and TEWL (R = 0.28, p = 0.004). After adjusting for smoking status and glove use, a significant correlation between urinary chromium concentrations and TEWL remained. Moreover, workers who smoked and had a high chromium exposure had significantly increased TEWL compared to nonsmokers with low chromium exposure (p = 0.01). Skin barrier function of cement workers may have been disrupted by chromium in cement, and smoking might significantly enhance such skin barrier perturbation with chromium exposure. Decreased chromium skin exposure and smoking cessation should be encouraged at work. © The Author(s) 2015.

Laser induced autofluorescence for diagnosis of non-melanoma skin cancer

Science.gov (United States)

Drakaki, E.; Makropoulou, M.; Serafetinides, A. A.; Merlemis, N.; Kalatzis, I.; Sianoudis, I. A.; Batsi, O.; Christofidou, E.; Stratigos, A. J.; Katsambas, A. D.; Antoniou, Ch.

2015-01-01

Non melanoma skin cancer is one of the most frequent malignant tumors among humans. A non-invasive technique, with high sensitivity and high specificity, would be the most suitable method for basal cell carcinoma (BCC) or other malignancies diagnostics, instead of the well established biopsy and histopathology examination. In the last decades, a non-invasive, spectroscopic diagnostic method was introduced, the laser induced fluorescence (LIF), which could generate an image contrast between different states of skin tissue. The noninvasiveness consists in that this biophotonic method do not require tissue sample excision, what is necessary in histopathology characterization and biochemical analysis of the skin tissue samples, which is worldwide used as an evaluation gold standard. The object of this study is to establish the possibilities of a relatively portable system for laser induced skin autofluorescence to differentiate malignant from nonmalignant skin lesions. Unstained human skin samples, excised from humans undergoing biopsy examination, were irradiated with a Nd:YAG-3ω laser (λ=355 nm, 6 ns), used as an excitation source for the autofluorescence measurements. A portable fiber-based spectrometer was used to record fluorescence spectra of the sites of interest. The ex vivo results, obtained with this spectroscopic technique, were correlated with the histopathology results. After the analysis of the fluorescence spectra of almost 60 skin tissue areas, we developed an algorithm to distinguish different types of malignant lesions, including inflammatory areas. Optimization of the data analysis and potential use of LIF spectroscopy with 355 nm Nd:YAG laser excitation of tissue autofluorescence for clinical applications are discussed.

Andrographolide Sodium Bisulfate Prevents UV-Induced Skin Photoaging through Inhibiting Oxidative Stress and Inflammation

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Janis Ya-Xian Zhan

2016-01-01

Full Text Available Andrographolide sodium bisulfate (ASB, a water-soluble form made from andrographolide through sulfonating reaction, is an antioxidant and anti-inflammatory drug; however, the antiphotoaging effect of ASB has still not been revealed. Oxidative stress and inflammation are known to be responsible for ultraviolet (UV irradiation induced skin damage and consequently premature aging. In this study, we aimed at examining the effect of ASB on UV-induced skin photoaging of mice by physiological and histological analysis of skin and examination of skin antioxidant enzymes and immunity analyses. Results showed that topical administration of ASB suppressed the UV-induced skin thickness, elasticity, wrinkles, and water content, while ASB, especially at dose of 3.6 mg/mouse, increased the skin collagen content by about 53.17%, decreased the epidermal thickness by about 41.38%, and prevented the UV-induced disruption of collagen fibers and elastic fibers. Furthermore, ASB decreased MDA level by about 40.21% and upregulated the activities of SOD and CAT and downregulated the production of IL-1β, IL-6, IL-10, and TNF-α in UV-irradiated mice. Our study confirmed the protective effect of ASB against UV-induced photoaging and initially indicated that this effect can be attributed to its antioxidant and anti-inflammatory activities in vivo, suggesting that ASB may be a potential antiphotoaging agent.

Andrographolide Sodium Bisulfate Prevents UV-Induced Skin Photoaging through Inhibiting Oxidative Stress and Inflammation

Science.gov (United States)

Zhan, Janis Ya-Xian; Wang, Xiu-Fen; Liu, Yu-Hong; Zhang, Zhen-Biao; Wang, Lan; Chen, Jian-Nan; Huang, Song; Zeng, Hui-Fang; Lai, Xiao-Ping

2016-01-01

Andrographolide sodium bisulfate (ASB), a water-soluble form made from andrographolide through sulfonating reaction, is an antioxidant and anti-inflammatory drug; however, the antiphotoaging effect of ASB has still not been revealed. Oxidative stress and inflammation are known to be responsible for ultraviolet (UV) irradiation induced skin damage and consequently premature aging. In this study, we aimed at examining the effect of ASB on UV-induced skin photoaging of mice by physiological and histological analysis of skin and examination of skin antioxidant enzymes and immunity analyses. Results showed that topical administration of ASB suppressed the UV-induced skin thickness, elasticity, wrinkles, and water content, while ASB, especially at dose of 3.6 mg/mouse, increased the skin collagen content by about 53.17%, decreased the epidermal thickness by about 41.38%, and prevented the UV-induced disruption of collagen fibers and elastic fibers. Furthermore, ASB decreased MDA level by about 40.21% and upregulated the activities of SOD and CAT and downregulated the production of IL-1β, IL-6, IL-10, and TNF-α in UV-irradiated mice. Our study confirmed the protective effect of ASB against UV-induced photoaging and initially indicated that this effect can be attributed to its antioxidant and anti-inflammatory activities in vivo, suggesting that ASB may be a potential antiphotoaging agent. PMID:26903706

Skin Rejuvenation with Non-Invasive Pulsed Electric Fields

Science.gov (United States)

Golberg, Alexander; Khan, Saiqa; Belov, Vasily; Quinn, Kyle P.; Albadawi, Hassan; Felix Broelsch, G.; Watkins, Michael T.; Georgakoudi, Irene; Papisov, Mikhail; Mihm Jr., Martin C.; Austen Jr., William G.; Yarmush, Martin L.

2015-01-01

Degenerative skin diseases affect one third of individuals over the age of sixty. Current therapies use various physical and chemical methods to rejuvenate skin; but since the therapies affect many tissue components including cells and extracellular matrix, they may also induce significant side effects, such as scarring. Here we report on a new, non-invasive, non-thermal technique to rejuvenate skin with pulsed electric fields. The fields destroy cells while simultaneously completely preserving the extracellular matrix architecture and releasing multiple growth factors locally that induce new cells and tissue growth. We have identified the specific pulsed electric field parameters in rats that lead to prominent proliferation of the epidermis, formation of microvasculature, and secretion of new collagen at treated areas without scarring. Our results suggest that pulsed electric fields can improve skin function and thus can potentially serve as a novel non-invasive skin therapy for multiple degenerative skin diseases. PMID:25965851

Impaired Skin Barrier Due to Sebaceous Gland Atrophy in the Latent Stage of Radiation-Induced Skin Injury: Application of Non-Invasive Diagnostic Methods

Directory of Open Access Journals (Sweden)

Hyosun Jang

2018-01-01

Full Text Available Radiation-induced skin injury can take the form of serious cutaneous damage and have specific characteristics. Asymptomatic periods are classified as the latent stage. The skin barrier plays a critical role in the modulation of skin permeability and hydration and protects the body against a harsh external environment. However, an analysis on skin barrier dysfunction against radiation exposure in the latent stage has not been conducted. Thus, we investigated whether the skin barrier is impaired by irradiation in the latent stage and aimed to identify the molecules involved in skin barrier dysfunction. We analyzed skin barrier function and its components in SKH1 mice that received 20 and 40 Gy local irradiation. Increased transepidermal water loss and skin pH were observed in the latent stage of the irradiated skin. Skin barrier components, such as structural proteins and lipid synthesis enzymes in keratinocyte, increased in the irradiated group. Interestingly, we noted sebaceous gland atrophy and increased serine protease and inflammatory cytokines in the irradiated skin during the latent period. This finding indicates that the main factor of skin barrier dysfunction in the latent stage of radiation-induced skin injury is sebaceous gland deficiency, which could be an intervention target for skin barrier impairment.

Chemical signals of fish skin for the attachment response of Acanthostomum brauni cercariae.

Science.gov (United States)

Haas, W; de Nuñez, M O

1988-01-01

The chemical signals of the skin surface of fish, which stimulate the attachment responses of Acanthostomum brauni cercariae, were identified by offering chemicals and fish-skin extracts in agarose substrates to the cercariae. Smaller molecules such as amino acids, fatty acids, monosaccharides, electrolytes, urea, and carbonate solutions did not stimulate attachments, but hyaluronic acid had some effects. Bovine submaxillary glycoproteins had a strong stimulating activity that disappeared after neuraminidase digestion. The stimulating components of the skin surface of fish were hydrophilic substances with molecular weights of more than 10,000. They were sensitive to neuraminidase digestion but not to hyaluronidase digestion and thus can be identified as glycoproteins. A. brauni cercariae respond only to the complete glycoprotein molecules and not to their monosaccharide components. The known attachment triggers of other cercariae are small molecules. Large glycoproteins as host signals for A. brauni cercariae may be an adaptation to muddy habitats, where various substances with low molecular weights may interfere with the host identification.

Endogenous UVA-photosensitizers: mediators of skin photodamage and novel targets for skin photoprotection.

Science.gov (United States)

Wondrak, Georg T; Jacobson, Myron K; Jacobson, Elaine L

2006-02-01

Endogenous chromophores in human skin serve as photosensitizers involved in skin photocarcinogenesis and photoaging. Absorption of solar photons, particularly in the UVA region, induces the formation of photoexcited states of skin photosensitizers with subsequent generation of reactive oxygen species (ROS), organic free radicals and other toxic photoproducts that mediate skin photooxidative stress. The complexity of endogenous skin photosensitizers with regard to molecular structure, pathways of formation, mechanisms of action, and the diversity of relevant skin targets has hampered progress in this area of photobiology and most likely contributed to an underestimation of the importance of endogenous sensitizers in skin photodamage. Recently, UVA-fluorophores in extracellular matrix proteins formed posttranslationally as a consequence of enzymatic maturation or spontaneous chemical damage during chronological and actinic aging have been identified as an abundant source of light-driven ROS formation in skin upstream of photooxidative cellular stress. Importantly, sensitized skin cell photodamage by this bystander mechanism occurs after photoexcitation of sensitizers contained in skin structural proteins without direct cellular photon absorption thereby enhancing the potency and range of phototoxic UVA action in deeper layers of skin. The causative role of photoexcited states in skin photodamage suggests that direct molecular antagonism of photosensitization reactions using physical quenchers of photoexcited states offers a novel chemopreventive opportunity for skin photoprotection.

UVA-induced protection of skin through the induction of heme oxygenase-1.

Science.gov (United States)

Xiang, Yuancai; Liu, Gang; Yang, Li; Zhong, Julia Li

2011-12-01

UVA (320-400 nm) and UVB (290-320 nm) are the major components of solar UV irradiation, which is associated with various pathological conditions. UVB causes direct damage to DNA of epidermal cells and is mainly responsible for erythema, immunosuppression, photoaging, and skin cancer. UVA has oxidizing properties that can cause damage or enhance UVB damaging effects on skin. On the other hand, UVA can also lead to high levels of heme oxygenase-1 (HO-1) expression of cells that can provide an antioxidant effect on skin as well as anti-inflammatory properties in mammals and rodents. Therefore, this review focuses on the potential protection of UVA wavebands for the skin immune response, instead of mechanisms that underlie UVA-induced damage. Also, the role of HO-1 in UVA-mediated protection against UVB-induced immunosuppression in skin will be summarized. Thus, this review facilitates further understanding of potential beneficial mechanisms of UVA irradiation, and using the longer UVA (UVA1, 340-400 nm) in combination with HO-1 for phototherapy and skin protection against sunlight exposure.

Protective effect of gelatin and gelatin hydrolysate from salmon skin on UV irradiation-induced photoaging of mice skin

Science.gov (United States)

Chen, Tiejun; Hou, Hu; Lu, Jiaohan; Zhang, Kai; Li, Bafang

2016-08-01

The objective of this study was to investigate the effect of gelatin (SG) isolated from salmon skin and its hydrolysate (SGH) on photoaging skin, and the mechanism responsible for anti-photoaging. The average molecular weights of SG and SGH were 65 kDa and 873 Da, respectively. The amino acid compositions of SG and SGH were similar. Both of them were abundant in hydrophobic amino acids. Twenty-five peptides were identified from SGH. SG and SGH could improve UV irradiation-induced pathological changes of macroscopical tissue texture and skin morphology. Hydroxyproline content is an indicator of matrix collagen content, SG and SGH could inhibit the decrease of hydroxyproline content in photoaging skin in a dose dependent manner. In addition, SG and SGH could alleviate UV irradiation-induced oxidative damages to skin by increasing the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), increasing the content of glutathione (GSH) and decreasing the content of malonaldehyde (MDA). Moreover, SG and SGH could enhance immune regulation system by increasing the thymus index. Thus, the anti-photoaging mechanisms of SG and SGH were by inhibiting the depletion of antioxidant defense components, involving in the synthesis of collagen and enhancing the function of immune system. Besides, SGH showed a better result in protecting skin from photoaging than SG.

p53 modulates the AMPK inhibitor compound C induced apoptosis in human skin cancer cells

Energy Technology Data Exchange (ETDEWEB)

Huang, Shi-Wei [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Wu, Chun-Ying [Division of Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wang, Yen-Ting [Department of Medical Research and Education, Cheng Hsin General Hospital, Taipei, Taiwan (China); Kao, Jun-Kai [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Department of Pediatrics, Children' s Hospital, Changhua Christian Hospital, Changhua, Taiwan (China); Lin, Chi-Chen; Chang, Chia-Che; Mu, Szu-Wei; Chen, Yu-Yu [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Chiu, Husan-Wen [Institute of Biotechnology, National Cheng-Kung University, Tainan, Taiwan (China); Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan (China); Chang, Chuan-Hsun [Department of Surgical Oncology, Cheng Hsin General Hospital, Taipei, Taiwan (China); Department of Nutrition Therapy, Cheng Hsin General Hospital, Taipei, Taiwan (China); School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan (China); Liang, Shu-Mei [Institute of Biotechnology, National Cheng-Kung University, Tainan, Taiwan (China); Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan (China); Chen, Yi-Ju [Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Huang, Jau-Ling [Department of Bioscience Technology, Chang Jung Christian University, Tainan, Taiwan (China); Shieh, Jeng-Jer, E-mail: shiehjj@vghtc.gov.tw [Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan (China); Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan (China)

2013-02-15

Compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), has been reported to cause apoptotic cell death in myeloma, breast cancer cells and glioma cells. In this study, we have demonstrated that compound C not only induced autophagy in all tested skin cancer cell lines but also caused more apoptosis in p53 wildtype skin cancer cells than in p53-mutant skin cancer cells. Compound C can induce upregulation, phosphorylation and nuclear translocalization of the p53 protein and upregulate expression of p53 target genes in wildtype p53-expressing skin basal cell carcinoma (BCC) cells. The changes of p53 status were dependent on DNA damage which was caused by compound C induced reactive oxygen species (ROS) generation and associated with activated ataxia-telangiectasia mutated (ATM) protein. Using the wildtype p53-expressing BCC cells versus stable p53-knockdown BCC sublines, we present evidence that p53-knockdown cancer cells were much less sensitive to compound C treatment with significant G2/M cell cycle arrest and attenuated the compound C-induced apoptosis but not autophagy. The compound C induced G2/M arrest in p53-knockdown BCC cells was associated with the sustained inactive Tyr15 phosphor-Cdc2 expression. Overall, our results established that compound C-induced apoptosis in skin cancer cells was dependent on the cell's p53 status. - Highlights: ► Compound C caused more apoptosis in p53 wildtype than p53-mutant skin cancer cells. ► Compound C can upregulate p53 expression and induce p53 activation. ► Compound C induced p53 effects were dependent on ROS induced DNA damage pathway. ► p53-knockdown attenuated compound C-induced apoptosis but not autophagy. ► Compound C-induced apoptosis in skin cancer cells was dependent on p53 status.

p53 modulates the AMPK inhibitor compound C induced apoptosis in human skin cancer cells

International Nuclear Information System (INIS)

Huang, Shi-Wei; Wu, Chun-Ying; Wang, Yen-Ting; Kao, Jun-Kai; Lin, Chi-Chen; Chang, Chia-Che; Mu, Szu-Wei; Chen, Yu-Yu; Chiu, Husan-Wen; Chang, Chuan-Hsun; Liang, Shu-Mei; Chen, Yi-Ju; Huang, Jau-Ling; Shieh, Jeng-Jer

2013-01-01

Compound C, a well-known inhibitor of the intracellular energy sensor AMP-activated protein kinase (AMPK), has been reported to cause apoptotic cell death in myeloma, breast cancer cells and glioma cells. In this study, we have demonstrated that compound C not only induced autophagy in all tested skin cancer cell lines but also caused more apoptosis in p53 wildtype skin cancer cells than in p53-mutant skin cancer cells. Compound C can induce upregulation, phosphorylation and nuclear translocalization of the p53 protein and upregulate expression of p53 target genes in wildtype p53-expressing skin basal cell carcinoma (BCC) cells. The changes of p53 status were dependent on DNA damage which was caused by compound C induced reactive oxygen species (ROS) generation and associated with activated ataxia-telangiectasia mutated (ATM) protein. Using the wildtype p53-expressing BCC cells versus stable p53-knockdown BCC sublines, we present evidence that p53-knockdown cancer cells were much less sensitive to compound C treatment with significant G2/M cell cycle arrest and attenuated the compound C-induced apoptosis but not autophagy. The compound C induced G2/M arrest in p53-knockdown BCC cells was associated with the sustained inactive Tyr15 phosphor-Cdc2 expression. Overall, our results established that compound C-induced apoptosis in skin cancer cells was dependent on the cell's p53 status. - Highlights: ► Compound C caused more apoptosis in p53 wildtype than p53-mutant skin cancer cells. ► Compound C can upregulate p53 expression and induce p53 activation. ► Compound C induced p53 effects were dependent on ROS induced DNA damage pathway. ► p53-knockdown attenuated compound C-induced apoptosis but not autophagy. ► Compound C-induced apoptosis in skin cancer cells was dependent on p53 status

Irradiation of skin with visible light induces reactive oxygen species and matrix-degrading enzymes.

Science.gov (United States)

Liebel, Frank; Kaur, Simarna; Ruvolo, Eduardo; Kollias, Nikiforos; Southall, Michael D

2012-07-01

Daily skin exposure to solar radiation causes cells to produce reactive oxygen species (ROS), which are a primary factor in skin damage. Although the contribution of the UV component to skin damage has been established, few studies have examined the effects of non-UV solar radiation on skin physiology. Solar radiation comprises UV, and thus the purpose of this study was to examine the physiological response of skin to visible light (400-700 nm). Irradiation of human skin equivalents with visible light induced production of ROS, proinflammatory cytokines, and matrix metalloproteinase (MMP)-1 expression. Commercially available sunscreens were found to have minimal effects on reducing visible light-induced ROS, suggesting that UVA/UVB sunscreens do not protect the skin from visible light-induced responses. Using clinical models to assess the generation of free radicals from oxidative stress, higher levels of free radical activity were found after visible light exposure. Pretreatment with a photostable UVA/UVB sunscreen containing an antioxidant combination significantly reduced the production of ROS, cytokines, and MMP expression in vitro, and decreased oxidative stress in human subjects after visible light irradiation. Taken together, these findings suggest that other portions of the solar spectrum aside from UV, particularly visible light, may also contribute to signs of premature photoaging in skin.

Main approaches for delivering antioxidant vitamins through the skin to prevent skin ageing.

Science.gov (United States)

Gašperlin, Mirjana; Gosenca, Mirjam

2011-07-01

One of the major contributions to skin photoageing and diseases is oxidative stress, caused by UV radiation inducing reactive oxygen and nitrogen species. Successful prophylaxis and therapy would necessitate control of the oxidant/antioxidant balance at the affected site, which can be achieved through the external supply of endogenous antioxidants. This review discusses possible strategies for dermal delivery of the antioxidant vitamins E and C, as oral supplementation has proved insufficient. These antioxidants have low skin bioavailability, owing to their poor solubility, inefficient skin permeability, or instability during storage. These drawbacks can be overcome by various approaches, such as chemical modification of the vitamins and the use of new colloidal drug delivery systems. New knowledge is included about the importance of: enhancing the endogenous skin antioxidant defense through external supply; the balance between various skin antioxidants; factors that can improve the skin bioavailability of antioxidants; and new delivery systems, such as microemulsions, used to deliver vitamins C and E into the skin simultaneously. A promising strategy for enhancing skin protection from oxidative stress is to support the endogenous antioxidant system, with antioxidants containing products that are normally present in the skin.

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-06-27

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

Mast cells are dispensable for normal and activin-promoted wound healing and skin carcinogenesis.

Science.gov (United States)

Antsiferova, Maria; Martin, Caroline; Huber, Marcel; Feyerabend, Thorsten B; Förster, Anja; Hartmann, Karin; Rodewald, Hans-Reimer; Hohl, Daniel; Werner, Sabine

2013-12-15

The growth and differentiation factor activin A is a key regulator of tissue repair, inflammation, fibrosis, and tumorigenesis. However, the cellular targets, which mediate the different activin functions, are still largely unknown. In this study, we show that activin increases the number of mature mast cells in mouse skin in vivo. To determine the relevance of this finding for wound healing and skin carcinogenesis, we mated activin transgenic mice with CreMaster mice, which are characterized by Cre recombinase-mediated mast cell eradication. Using single- and double-mutant mice, we show that loss of mast cells neither affected the stimulatory effect of overexpressed activin on granulation tissue formation and reepithelialization of skin wounds nor its protumorigenic activity in a model of chemically induced skin carcinogenesis. Furthermore, mast cell deficiency did not alter wounding-induced inflammation and new tissue formation or chemically induced angiogenesis and tumorigenesis in mice with normal activin levels. These findings reveal that mast cells are not major targets of activin during wound healing and skin cancer development and also argue against nonredundant functions of mast cells in wound healing and skin carcinogenesis in general.

Skin aspergillosis induced in the region of radiation ulcer

International Nuclear Information System (INIS)

Niimura, Yumiko; Nakauchi, Yohichi; Ushijima, Tsugako

1980-01-01

A case of skin aspergillosis in the region of radiation ulcer which was caused by Aspergillus fumigatus was reported. The patient was a 51 year-old man. This fungal infection was probably induced by a local factor, that is, chronic radiation ulcer. Histological findings suggested that Aspergillus fumigatus which increased saprophytically at the beginning possessed parasitic nature gradually, invaded into connective tissues in the deep layer of true skin, and made radiation ulcer more intractable. (Tsunoda, M.)

Calculating the dermal flux of chemicals with OELs based on their molecular structure: An attempt to assign the skin notation.

Science.gov (United States)

Kupczewska-Dobecka, Małgorzata; Jakubowski, Marek; Czerczak, Sławomir

2010-09-01

Our objectives included calculating the permeability coefficient and dermal penetration rates (flux value) for 112 chemicals with occupational exposure limits (OELs) according to the LFER (linear free-energy relationship) model developed using published methods. We also attempted to assign skin notations based on each chemical's molecular structure. There are many studies available where formulae for coefficients of permeability from saturated aqueous solutions (K(p)) have been related to physicochemical characteristics of chemicals. The LFER model is based on the solvation equation, which contains five main descriptors predicted from chemical structure: solute excess molar refractivity, dipolarity/polarisability, summation hydrogen bond acidity and basicity, and the McGowan characteristic volume. Descriptor values, available for about 5000 compounds in the Pharma Algorithms Database were used to calculate permeability coefficients. Dermal penetration rate was estimated as a ratio of permeability coefficient and concentration of chemical in saturated aqueous solution. Finally, estimated dermal penetration rates were used to assign the skin notation to chemicals. Defined critical fluxes defined from the literature were recommended as reference values for skin notation. The application of Abraham descriptors predicted from chemical structure and LFER analysis in calculation of permeability coefficients and flux values for chemicals with OELs was successful. Comparison of calculated K(p) values with data obtained earlier from other models showed that LFER predictions were comparable to those obtained by some previously published models, but the differences were much more significant for others. It seems reasonable to conclude that skin should not be characterised as a simple lipophilic barrier alone. Both lipophilic and polar pathways of permeation exist across the stratum corneum. It is feasible to predict skin notation on the basis of the LFER and other published

Leptin deficiency-induced obesity exacerbates ultraviolet B radiation-induced cyclooxygenase-2 expression and cell survival signals in ultraviolet B-irradiated mouse skin

International Nuclear Information System (INIS)

Sharma, Som D.; Katiyar, Santosh K.

2010-01-01

Obesity has been implicated in several inflammatory diseases and in different types of cancer. Chronic inflammation induced by exposure to ultraviolet (UV) radiation has been implicated in various skin diseases, including melanoma and nonmelanoma skin cancers. As the relationship between obesity and susceptibility to UV radiation-caused inflammation is not clearly understood, we assessed the role of obesity on UVB-induced inflammation, and mediators of this inflammatory response, using the genetically obese (leptin-deficient) mouse model. Leptin-deficient obese (ob/ob) mice and wild-type counterparts (C57/BL6 mice) were exposed to UVB radiation (120 mJ/cm 2 ) on alternate days for 1 month. The mice were then euthanized and skin samples collected for analysis of biomarkers of inflammatory responses using immunohistochemistry, western blotting, ELISA and real-time PCR. Here, we report that the levels of inflammatory responses were higher in the UVB-exposed skin of the ob/ob obese mice than those in the UVB-exposed skin of the wild-type non-obese mice. The levels of UVB-induced cyclooxygenase-2 expression, prostaglandin-E 2 production, proinflammatory cytokines (i.e., tumor necrosis factor-α, interleukin-1β, interleukin-6), and proliferating cell nuclear antigen and cell survival signals (phosphatidylinositol-3-kinase and p-Akt-Ser 473 ) were higher in the skin of the ob/ob obese mice than the those in skin of their wild-type non-obese counterparts. Compared with the wild-type non-obese mice, the leptin-deficient obese mice also exhibited greater activation of NF-κB/p65 and fewer apoptotic cells in the UVB-irradiated skin. Our study suggests for the first time that obesity in mice is associated with greater susceptibility to UVB-induced inflammatory responses and, therefore, obesity may increase susceptibility to UVB-induced inflammation-associated skin diseases, including the risk of skin cancer.

Effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in mice.

Science.gov (United States)

Satoh, T; Murata, M; Iwabuchi, N; Odamaki, T; Wakabayashi, H; Yamauchi, K; Abe, F; Xiao, J Z

2015-01-01

Probiotics have been shown to have a preventative effect on skin photoaging induced by short term UV irradiation, however, the underlying mechanisms and the effect of probiotics on skin photoaging induced by chronic UV irradiation remain unclear. In this study, we investigated the effect of Bifidobacterium breve B-3 on skin photoaging induced by chronic UV irradiation in hairless mice. Mice were irradiated with UVB three times weekly and orally administered B. breve B-3 (2×10(9) cfu/mouse /day) for 7 weeks. Nonirradiated mice and UVB-irradiated mice without probiotic treatment were used as controls. B. breve B-3 significantly suppressed the changes of transepidermal water loss, skin hydration, epidermal thickening and attenuated the damage to the tight junction structure and basement membrane induced by chronic UVB irradiation. Administration of B. breve B-3 tended to suppress the UV-induced interleukin-1β production in skin (P=0.09). These results suggest that B. breve B-3 could potentially be used to prevent photoaging induced by chronic UV irradiation.

Chronologic and actinically induced aging in human facial skin

International Nuclear Information System (INIS)

Gilchrest, B.A.; Szabo, G.; Flynn, E.; Goldwyn, R.M.

1983-01-01

Clinical and histologic stigmata of aging are much more prominent in habitually sun-exposed skin than in sun-protected skin, but other possible manifestations of actinically induced aging are almost unexplored. We have examined the interrelation of chronologic and actinic aging using paired preauricular (sun-exposed) and postauricular (sun-protected) skin specimens. Keratinocyte cultures derived from sun-exposed skin consistently had a shorter in vitro lifespan but increased plating efficiency compared with cultures derived from adjacent sun-protected skin of the same individual, confirming a previous study of different paired body sites. Electron microscopic histologic sections revealed focal abnormalities of keratinocyte proliferation and alignment in vitro especially in those cultures derived from sun-exposed skin and decreased intercellular contact in stratified colonies at late passage, regardless of donor site. One-micron histologic sections of the original biopsy specimens revealed no striking site-related keratinocyte alterations, but sun-exposed specimens had fewer epidermal Langerhans cells (p less than 0.001), averaging approximately 50 percent the number in sun-protected skin, a possible exaggeration of the previously reported age-associated decrease in this cell population. These data suggest that sun exposure indeed accelerates aging by several criteria and that, regardless of mechanism, environmental factors may adversely affect the appearance and function of aging skin in ways amenable to experimental quantitation

Resident CD141 (BDCA3)+ dendritic cells in human skin produce IL-10 and induce regulatory T cells that suppress skin inflammation.

Science.gov (United States)

Chu, Chung-Ching; Ali, Niwa; Karagiannis, Panagiotis; Di Meglio, Paola; Skowera, Ania; Napolitano, Luca; Barinaga, Guillermo; Grys, Katarzyna; Sharif-Paghaleh, Ehsan; Karagiannis, Sophia N; Peakman, Mark; Lombardi, Giovanna; Nestle, Frank O

2012-05-07

Human skin immune homeostasis, and its regulation by specialized subsets of tissue-residing immune sentinels, is poorly understood. In this study, we identify an immunoregulatory tissue-resident dendritic cell (DC) in the dermis of human skin that is characterized by surface expression of CD141, CD14, and constitutive IL-10 secretion (CD141(+) DDCs). CD141(+) DDCs possess lymph node migratory capacity, induce T cell hyporesponsiveness, cross-present self-antigens to autoreactive T cells, and induce potent regulatory T cells that inhibit skin inflammation. Vitamin D(3) (VitD3) promotes certain phenotypic and functional properties of tissue-resident CD141(+) DDCs from human blood DCs. These CD141(+) DDC-like cells can be generated in vitro and, once transferred in vivo, have the capacity to inhibit xeno-graft versus host disease and tumor alloimmunity. These findings suggest that CD141(+) DDCs play an essential role in the maintenance of skin homeostasis and in the regulation of both systemic and tumor alloimmunity. Finally, VitD3-induced CD141(+) DDC-like cells have potential clinical use for their capacity to induce immune tolerance.

Further development of LLNA:DAE method as stand-alone skin-sensitization testing method and applied for evaluation of relative skin-sensitizing potency between chemicals.

Science.gov (United States)

Yamashita, Kunihiko; Shinoda, Shinsuke; Hagiwara, Saori; Itagaki, Hiroshi

2015-04-01

To date, there has been no well-established local lymph node assay (LLNA) that includes an elicitation phase. Therefore, we developed a modified local lymph node assay with an elicitation phase (LLNA:DAE) to discriminate true skin sensitizers from chemicals that gave borderline positive results and previously reported this assay. To develop the LLNA:DAE method as a useful stand-alone testing method, we investigated the complete procedure for the LLNA:DAE method using hexyl cinnamic aldehyde (HCA), isoeugenol, and 2,4-dinitrochlorobenzene (DNCB) as test compounds. We defined the LLNA:DAE procedure as follows: in the dose-finding test, four concentrations of chemical applied to dorsum of the right ear on days 1, 2, and 3 and dorsum of both ears on day 10. Ear thickness and skin irritation score were measured on days 1, 3, 5, 10, and 12. Local lymph nodes were excised and weighed on day 12. The test dose for the primary LLNA:DAE study was selected as the dose that gave the highest left ear lymph node weight in the dose-finding study, or the lowest dose that produced a left ear lymph node of over 4 mg. This procedure was validated using nine different chemicals. Furthermore, qualitative relationship was observed between the degree of elicitation response in the left ear lymph node and the skin sensitizing potency of 32 chemicals tested in this study and the previous study. These results indicated that LLNA:DAE method was as first LLNA method that was able to evaluate the skin sensitizing potential and potency in elicitation response.

Investigation on the effect of developed product and new food for radiation-induced skin damage

Energy Technology Data Exchange (ETDEWEB)

Kim, Sung Ho; Kim, Jong Chun; Bae, Chun Sik; Kim, Se Ra; Lee, Hae Jun; Bang, Dae Won; Lee, Jin Hee; Kim, Joong Sun; Ki, Sun Ah; Song, Myung Seop [Chonnam National University, Gwangju (Korea, Republic of)

2007-07-15

In vivo evaluation of the developed pilot product on the skin protection against UV irradiation and screening of new candidate materials. Project Results are Establishment of experimental methods for 3 morphological indices of UV-induced skin damages -Establishment of experimental methods for whitening effect evaluation -Evaluation of HemoHIM administration on the skin damage indices -Evaluation of HemoHIM skin application on the skin damage indices -Evaluation of HemoTonic administration on the skin damage indices -Evaluation of HemoTonic skin application on the skin damage indices -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 1 -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 2 -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 3 -Evaluation of HemoHIM on the antiinflamatory effects in the TNBS-induced colitis -Evaluation of HemoHIM on the anti-wrinkle effects in the skin -Evaluation of HemoHIM on the protective effects on the skin tissue (epidermal thickening, dermal cellularity, dermal cyst) -Evaluation of HemoHIM on the protective effects on the skin tumor development

Investigation on the effect of developed product and new food for radiation-induced skin damage

International Nuclear Information System (INIS)

Kim, Sung Ho; Kim, Jong Chun; Bae, Chun Sik; Kim, Se Ra; Lee, Hae Jun; Bang, Dae Won; Lee, Jin Hee; Kim, Joong Sun; Ki, Sun Ah; Song, Myung Seop

2007-07-01

In vivo evaluation of the developed pilot product on the skin protection against UV irradiation and screening of new candidate materials. Project Results are Establishment of experimental methods for 3 morphological indices of UV-induced skin damages -Establishment of experimental methods for whitening effect evaluation -Evaluation of HemoHIM administration on the skin damage indices -Evaluation of HemoHIM skin application on the skin damage indices -Evaluation of HemoTonic administration on the skin damage indices -Evaluation of HemoTonic skin application on the skin damage indices -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 1 -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 2 -Evaluation of HemoHIM on the antiinflamatory effects in the inflammation stage 3 -Evaluation of HemoHIM on the antiinflamatory effects in the TNBS-induced colitis -Evaluation of HemoHIM on the anti-wrinkle effects in the skin -Evaluation of HemoHIM on the protective effects on the skin tissue (epidermal thickening, dermal cellularity, dermal cyst) -Evaluation of HemoHIM on the protective effects on the skin tumor development

Camphor induces cold and warm sensations with increases in skin and muscle blood flow in human.

Science.gov (United States)

Kotaka, Tomohiko; Kimura, Shoji; Kashiwayanagi, Makoto; Iwamoto, Jun

2014-01-01

Application of camphor to the skin has been empirically thought to improve blood circulation. However, camphor's effects on blood circulation to the skin and on thermal sensation have not been well elucidated. In this study, we examined its effects on the quality of sensation as well as on skin and muscle blood flow in human. Nine adults (average age 37±9.4 years) participated in the study. Petroleum jelly containing 5%, 10%, 20% camphor, or 2% menthol was separately applied to the skin on the medial side of one forearm of each subject. Just after the application, camphor at each concentration induced a cold sensation in a dose-dependent manner. Within 10 min, each subject reported that the cold sensation had faded, after which it was replaced by a warm sensation. As reported previously, a cold sensation was induced by application of 2% menthol, but the subjects did not adapt to that sensation. In addition, menthol did not induce a warm sensation at all. Application of menthol has been shown to increase blood flow in the skin. Finally, we measured blood flow in skin and muscle after the application of camphor or menthol. Application of camphor or menthol separately induced increases in local blood flow in the skin and muscle. The present results indicate that camphor induces both cold and warm sensations and improves blood circulation.

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

DEFF Research Database (Denmark)

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

2015-01-01

. In comparison, blood -derived in vitro differentiated Th2 cells only induced a weak response in a few of the mice. Thus, we conclude that human AD skin-derived T cells can induce a reaction in mouse skin through induction of a proliferative response in the mouse keratinocytes. This article is protected......In atopic dermatitis (AD), the inflammatory response between skin infiltrating T cells and keratinocytes is fundamental to the development of chronic lesional eczema. The aim of this study was to investigate whether skin-derived T cells from AD patients could induce an inflammatory response in mice...... through keratinocyte activation and consequently cause development of eczematous lesions. Punch biopsies of lesional skin from AD patients were used to establish skin-derived T cell cultures and which were transferred into NOD.Cg-Prkd(scid) Il2rg(tm1Sug) /JicTac (NOG) mice. We found that subcutaneous...

Differential role of basal keratinocytes in UV-induced immunosuppression and skin cancer

NARCIS (Netherlands)

J. Jans (Judith); G.A. Garinis (George); W. Schul; A. van Oudenaren (Adri); M.J. Moorhouse (Michael); M. Smid (Marcel); Y.-G. Sert (Yurda-Gul); A. van der Velde (Albertina); Y.M. Rijksen (Yvonne); F.R. de Gruijl (Frank); P.J. van der Spek (Peter); A. Yasui (Akira); J.H.J. Hoeijmakers (Jan); P.J. Leenen (Pieter); G.T.J. van der Horst (Gijsbertus)

2006-01-01

textabstractCyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs) comprise major UV-induced photolesions. If left unrepaired, these lesions can induce mutations and skin cancer, which is facilitated by UV-induced immunosuppression. Yet the contribution of lesion and cell type

In vivo study of the human skin by the method of laser-induced fluorescence spectroscopy

International Nuclear Information System (INIS)

Borisova, E.; Avramov, L.

2000-01-01

The goals of this study are to perform a preliminary evaluation of the diagnostic potential of noninvasive laser-induced auto-fluorescence spectroscopy (LIAFS) for human skin and optimize of detection and diagnosis of hollow organs and skin. In recent years, there has been growing interest in the use of laser-induced fluorescence to discriminate disease from normal surrounding tissue. The most fluorescence studies have used exogenous fluorophores of this discrimination. The laser-induced auto-fluorescence which is used for diagnosis of tissues in the human body avoids administration of any drugs. In this study a technique for optical biopsy of in vivo human skin is presented. The auto-fluorescence characterization of tissue relies on different spectral properties of tissues. It was demonstrated a differentiation between normal skin and skin with vitiligo. Two main endogenous fluorophores in the human skin account for most of the cellular auto-fluorescence for excitation wavelength 337 nm reduced from of nicotinamide adenine dinucleotide and collagen. The auto-fluorescence spectrum of human skin depend on main internal absorbers which are blood and melanin. In this study was described the effect caused by blood and melanin content on the shape of the auto-fluorescence spectrum of human skin. Human skin fluorescence spectrum might provide dermatologists with important information and such investigations are successfully used now in skin disease diagnostics, in investigation of the environmental factor impact or for evaluation of treatment efficiency. (authors)

Radiation-induced vascular lesions of the skin: an overview

NARCIS (Netherlands)

Flucke, U.E.; Requena, L.; Mentzel, T.

2013-01-01

Radiation-induced cutaneous vascular neoplasms occur infrequently and comprise benign, so-called atypical vascular lesions (AVL) and angiosarcomas (AS), often being high-grade malignant tumors. Both arise most frequently within previously irradiated skin in breast-conserving-treated mammary cancer

Inventory of the chemicals and the exposure of the workers' skin to these at two leather factories in Indonesia.

Science.gov (United States)

Febriana, Sri Awalia; Jungbauer, Frank; Soebono, Hardyanto; Coenraads, Pieter-Jan

2012-07-01

Tannery workers are exposed to hazardous chemicals. Tannery work is outsourced to newly industrialized countries (NICs) where attention into occupational health hazards is limited. In this study, we investigated the skin exposure to hazardous chemicals in tannery workers and determined the prevalence of occupational skin diseases (OSDs) at tanneries in a NIC. A cross-sectional study on the observation of the working process and an inventory and risk assessment of the chemicals used. Classification of chemicals as potential sensitizers/irritants and a qualitative assessment of exposure to these chemicals. Workers were examined and interviewed using Nordic Occupational Skin Questionnaire-2002/LONG. The risk of OSDs at the investigated tanneries was mainly related to the exposure of the workers' skin to chemicals in hot and humid environmental conditions. In 472 workers, 12% reported a current OSD and 9% reported a history of OSD. In 10% of all cases, an OSD was confirmed by a dermatologist and 7.4% had an occupational contact dermatitis (OCD). We observed that personal protective equipment (PPE) used was mainly because of skin problems in the past and not as a primary protection against OSD. We observed a high frequency and prolonged exposure to many skin hazardous factors in tannery work although PPE was relatively easily available and which was generally used as a secondary preventative measure. The observed point-prevalence in this study was at the same level as that reported for other high-risk OSDs in Western countries and other tanneries in NICs. However, the observed point-prevalence in this study was lower than that reported in India and Korea. The results of our study and those of other studies at tanneries from other NICs were probably influenced by Healthy Worker Survivor Effect (HWSE).

Radio-induced fibrosis of skin: contribution to its development and treatment

International Nuclear Information System (INIS)

Vozenin-Brotons, Marie-Catherine

1999-01-01

Fibrosis of skin is frequently observed after therapeutic and accidental irradiations, and is characterized by the appearance of activated fibroblasts called myo-fibroblasts and the accumulation of extracellular matrix compounds. We postulated that radiation fibrosis could be considered as a chronic scar, where constant production of activating signals are emitted, whereas no negative feed back regulation occur. However, recent studies demonstrated that radiation-induced fibrosis could be treated using therapeutic agents like the superoxide dismutase. In order to better understand the mechanisms leading to skin fibrosis, we studied both the early reactions and the late fibrotic tissue induced by high radiation doses in normal skin. In particular, we investigated in the role of growth factors in these reactions. The synthesis of TGF-β1 was found to be increased, both the epidermis and the dermis, immediately after irradiation. This overexpression sustained during the development and the persistence phases of fibrosis, suggesting that the immediate cellular response induce a cascade of activation for genes and proteins which will result in the late effect of radiation in skin. Furthermore, these observations showed that the TGF-β1 could be a target for anti-fibrotic treatment. In order to test this hypothesis and to investigate further in the mechanisms leading to fibrosis regression after SOD treatment, we develop normal and fibrosis-like reconstructed skin models. These reconstructed skins were treated with liposomal and carrier-free Cu/Zn SOD, and examined for their effects on cell number, apoptosis and phenotypic differentiation. The results showed that SOD did not induce myo-fibroblast cell death or apoptosis whereas it significantly reduced TGF-β1 expression, thus demonstrating that SOD might be considered as a potent antagonist of the major fibro-genic growth factor. We also found that SOD significantly lowered the levels of the myo-fibroblast marker �

Bleomycin-induced epithelial–mesenchymal transition in sclerotic skin of mice: Possible role of oxidative stress in the pathogenesis

Energy Technology Data Exchange (ETDEWEB)

Zhou, Cheng-Fan, E-mail: zhouchengfan@sohu.com [Institute of Dermatology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022 (China); Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui 230032 (China); Zhou, Deng-Chuan [Department of Emergency Medicine and Critical Care Medicine, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022 (China); Zhang, Jia-Xiang; Wang, Feng; Cha, Wan-Sheng [Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui 230032 (China); Wu, Chang-Hao [Department of Biochemistry and Physiology, Faculty of Health and Medical Sciences, University of Surrey (United Kingdom); Zhu, Qi-Xing, E-mail: zqxing@yeah.net [Institute of Dermatology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022 (China); Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui 230032 (China)

2014-06-15

Epithelial–mesenchymal transition (EMT) derived myofibroblasts are partly responsible for the increased collagen synthesis and deposition that occur in tissue fibrosis; however EMT occurrence in skin fibrosis and its mechanism remain unknown. The aim of this study was to investigate whether epithelial cells undergo EMT and determine the role of oxidative stress in this process. BALB/c mice were subcutaneously injected with bleomycin (BLM) or phosphate buffer saline (PBS) into the shaved back daily for 2, 3, and 4 weeks. Skin collagen deposition was evaluated by histopathology and Western blotting. EMT characteristics in the skin were determined by histopathology and immunofluorescent staining for E-cadherin and vimentin, which were further evaluated by Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR). To investigate the role of oxidative stress in EMT, the antioxidant N-acetylcysteine (NAC) was intraperitoneally (100 mg/kg body weight/day) injected daily for 3 weeks. The epithelial suprabasal cells were detached from the basement membrane zone (BMZ) in the sclerotic skin treated with BLM. Immunofluorescent staining indicated vimentin-positive epithelial cells frequently occurring in the thickened epidermis of BLM-treated mice. Western blotting and RT-PCR showed that the expression of E-cadherin was significantly decreased but that of vimentin significantly increased in the skin treated with BLM. NAC attenuated BLM induced oxidative damage, changes in E-cadherin and vimentin expressions and collagen deposition in the sclerotic skin of mice. This study provides the first evidence that BLM induces the EMT of the epithelial cells superficial to the basement membrane zone in the skin fibrosis. Oxidative stress may contribute, at least in part, to BLM induced EMT and skin fibrosis in mice. - Highlights: • We provided the first evidence that EMT occurred in BLM-induced skin fibrosis. • Epithelial cells superficial to the BMZ underwent

Bleomycin-induced epithelial–mesenchymal transition in sclerotic skin of mice: Possible role of oxidative stress in the pathogenesis

International Nuclear Information System (INIS)

Zhou, Cheng-Fan; Zhou, Deng-Chuan; Zhang, Jia-Xiang; Wang, Feng; Cha, Wan-Sheng; Wu, Chang-Hao; Zhu, Qi-Xing

2014-01-01

Epithelial–mesenchymal transition (EMT) derived myofibroblasts are partly responsible for the increased collagen synthesis and deposition that occur in tissue fibrosis; however EMT occurrence in skin fibrosis and its mechanism remain unknown. The aim of this study was to investigate whether epithelial cells undergo EMT and determine the role of oxidative stress in this process. BALB/c mice were subcutaneously injected with bleomycin (BLM) or phosphate buffer saline (PBS) into the shaved back daily for 2, 3, and 4 weeks. Skin collagen deposition was evaluated by histopathology and Western blotting. EMT characteristics in the skin were determined by histopathology and immunofluorescent staining for E-cadherin and vimentin, which were further evaluated by Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR). To investigate the role of oxidative stress in EMT, the antioxidant N-acetylcysteine (NAC) was intraperitoneally (100 mg/kg body weight/day) injected daily for 3 weeks. The epithelial suprabasal cells were detached from the basement membrane zone (BMZ) in the sclerotic skin treated with BLM. Immunofluorescent staining indicated vimentin-positive epithelial cells frequently occurring in the thickened epidermis of BLM-treated mice. Western blotting and RT-PCR showed that the expression of E-cadherin was significantly decreased but that of vimentin significantly increased in the skin treated with BLM. NAC attenuated BLM induced oxidative damage, changes in E-cadherin and vimentin expressions and collagen deposition in the sclerotic skin of mice. This study provides the first evidence that BLM induces the EMT of the epithelial cells superficial to the basement membrane zone in the skin fibrosis. Oxidative stress may contribute, at least in part, to BLM induced EMT and skin fibrosis in mice. - Highlights: • We provided the first evidence that EMT occurred in BLM-induced skin fibrosis. • Epithelial cells superficial to the BMZ underwent

Influence of chemical peeling on the skin stress response system.

Science.gov (United States)

Kimura, Ayako; Kanazawa, Nobuo; Li, Hong-Jin; Yonei, Nozomi; Yamamoto, Yuki; Furukawa, Fukumi

2012-07-01

Skin stress response system (SSRS) involves corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC)-derived peptides, such as adrenocorticotropic hormone (ACTH), a-melanocyte-stimulating hormone (MSH) and b-endorphin that are locally generated in response to locally provided stressors or proinflammatory cytokines. This system would restrict tissue damage and restore local homoeostasis. Trichloroacetic acid (TCA) is one of the most widely used peeling agents and applied for cosmetic treatment of photodamaged skin. However, the biological mechanism responsible for TCA peeling has yet to be fully determined. While our investigation focused on the inflammation and wound healing pathways, in the recent study, we have examined involvement of the SSRS as the third pathway. Mostly depending on our findings that TCA peeling activates the SSRS by inducing the POMC expression of keratinocytes in the CRH-independent manner, together with the results reported by other researchers, we can say that the biological effect of POMC seems to be responsible for the TCA-induced epidermal SSRS activation. © 2012 John Wiley & Sons A/S.

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

International Nuclear Information System (INIS)

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

2008-01-01

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

The Nrf2-inducers tanshinone I and dihydrotanshinone protect human skin cells and reconstructed human skin against solar simulated UV☆

Science.gov (United States)

Tao, Shasha; Justiniano, Rebecca; Zhang, Donna D.; Wondrak, Georg T.

2013-01-01

Exposure to solar ultraviolet (UV) radiation is a causative factor in skin photocarcinogenesis and photoaging, and an urgent need exists for improved strategies for skin photoprotection. The redox-sensitive transcription factor Nrf2 (nuclear factor-E2-related factor 2), a master regulator of the cellular antioxidant defense against environmental electrophilic insult, has recently emerged as an important determinant of cutaneous damage from solar UV, and the concept of pharmacological activation of Nrf2 has attracted considerable attention as a novel approach to skin photoprotection. In this study, we examined feasibility of using tanshinones, a novel class of phenanthrenequinone-based cytoprotective Nrf2 inducers derived from the medicinal plant Salvia miltiorrhiza, for protection of cultured human skin cells and reconstructed human skin against solar simulated UV. Using a dual luciferase reporter assay in human Hs27 dermal fibroblasts pronounced transcriptional activation of Nrf2 by four major tanshinones [tanshinone I (T-I), dihydrotanshinone (DHT), tanshinone IIA (T-II-A) and cryptotanshinone (CT)] was detected. In fibroblasts, the more potent tanshinones T-I and DHT caused a significant increase in Nrf2 protein half-life via blockage of ubiquitination, ultimately resulting in upregulated expression of cytoprotective Nrf2 target genes (GCLC, NQO1) with the elevation of cellular glutathione levels. Similar tanshinone-induced changes were also observed in HaCaT keratinocytes. T-I and DHT pretreatment caused significant suppression of skin cell death induced by solar simulated UV and riboflavin-sensitized UVA. Moreover, feasibility of tanshinone-based cutaneous photoprotection was tested employing a human skin reconstruct exposed to solar simulated UV (80 mJ/cm2 UVB; 1.53 J/cm2 UVA). The occurrence of markers of epidermal solar insult (cleaved procaspase 3, pycnotic nuclei, eosinophilic cytoplasm, acellular cavities) was significantly attenuated in DHT

The Nrf2-inducers tanshinone I and dihydrotanshinone protect human skin cells and reconstructed human skin against solar simulated UV.

Science.gov (United States)

Tao, Shasha; Justiniano, Rebecca; Zhang, Donna D; Wondrak, Georg T

2013-01-01

Exposure to solar ultraviolet (UV) radiation is a causative factor in skin photocarcinogenesis and photoaging, and an urgent need exists for improved strategies for skin photoprotection. The redox-sensitive transcription factor Nrf2 (nuclear factor-E2-related factor 2), a master regulator of the cellular antioxidant defense against environmental electrophilic insult, has recently emerged as an important determinant of cutaneous damage from solar UV, and the concept of pharmacological activation of Nrf2 has attracted considerable attention as a novel approach to skin photoprotection. In this study, we examined feasibility of using tanshinones, a novel class of phenanthrenequinone-based cytoprotective Nrf2 inducers derived from the medicinal plant Salvia miltiorrhiza, for protection of cultured human skin cells and reconstructed human skin against solar simulated UV. Using a dual luciferase reporter assay in human Hs27 dermal fibroblasts pronounced transcriptional activation of Nrf2 by four major tanshinones [tanshinone I (T-I), dihydrotanshinone (DHT), tanshinone IIA (T-II-A) and cryptotanshinone (CT)] was detected. In fibroblasts, the more potent tanshinones T-I and DHT caused a significant increase in Nrf2 protein half-life via blockage of ubiquitination, ultimately resulting in upregulated expression of cytoprotective Nrf2 target genes (GCLC, NQO1) with the elevation of cellular glutathione levels. Similar tanshinone-induced changes were also observed in HaCaT keratinocytes. T-I and DHT pretreatment caused significant suppression of skin cell death induced by solar simulated UV and riboflavin-sensitized UVA. Moreover, feasibility of tanshinone-based cutaneous photoprotection was tested employing a human skin reconstruct exposed to solar simulated UV (80 mJ/cm(2) UVB; 1.53 J/cm(2) UVA). The occurrence of markers of epidermal solar insult (cleaved procaspase 3, pycnotic nuclei, eosinophilic cytoplasm, acellular cavities) was significantly attenuated in DHT

The Nrf2-inducers tanshinone I and dihydrotanshinone protect human skin cells and reconstructed human skin against solar simulated UV

Directory of Open Access Journals (Sweden)

Shasha Tao

2013-01-01

Full Text Available Exposure to solar ultraviolet (UV radiation is a causative factor in skin photocarcinogenesis and photoaging, and an urgent need exists for improved strategies for skin photoprotection. The redox-sensitive transcription factor Nrf2 (nuclear factor-E2-related factor 2, a master regulator of the cellular antioxidant defense against environmental electrophilic insult, has recently emerged as an important determinant of cutaneous damage from solar UV, and the concept of pharmacological activation of Nrf2 has attracted considerable attention as a novel approach to skin photoprotection. In this study, we examined feasibility of using tanshinones, a novel class of phenanthrenequinone-based cytoprotective Nrf2 inducers derived from the medicinal plant Salvia miltiorrhiza, for protection of cultured human skin cells and reconstructed human skin against solar simulated UV. Using a dual luciferase reporter assay in human Hs27 dermal fibroblasts pronounced transcriptional activation of Nrf2 by four major tanshinones [tanshinone I (T-I, dihydrotanshinone (DHT, tanshinone IIA (T-II-A and cryptotanshinone (CT] was detected. In fibroblasts, the more potent tanshinones T-I and DHT caused a significant increase in Nrf2 protein half-life via blockage of ubiquitination, ultimately resulting in upregulated expression of cytoprotective Nrf2 target genes (GCLC, NQO1 with the elevation of cellular glutathione levels. Similar tanshinone-induced changes were also observed in HaCaT keratinocytes. T-I and DHT pretreatment caused significant suppression of skin cell death induced by solar simulated UV and riboflavin-sensitized UVA. Moreover, feasibility of tanshinone-based cutaneous photoprotection was tested employing a human skin reconstruct exposed to solar simulated UV (80 mJ/cm2 UVB; 1.53 J/cm2 UVA. The occurrence of markers of epidermal solar insult (cleaved procaspase 3, pycnotic nuclei, eosinophilic cytoplasm, acellular cavities was significantly attenuated in DHT

Monitoring UV-induced signalling pathways in an ex vivo skin organ culture model using phospho-antibody array.

Science.gov (United States)

Lenain, Christelle; Gamboa, Bastien; Perrin, Agnes; Séraïdaris, Alexia; Bertino, Béatrice; Rival, Yves; Bernardi, Mathieu; Piwnica, David; Méhul, Bruno

2018-05-01

We investigated UV-induced signalling in an ex vivo skin organ culture model using phospho-antibody array. Phosphorylation modulations were analysed in time-course experiments following exposure to solar-simulated UV and validated by Western blot analyses. We found that UV induced P-p38 and its substrates, P-ERK1/2 and P-AKT, which were previously shown to be upregulated by UV in cultured keratinocytes and in vivo human skin. This indicates that phospho-antibody array applied to ex vivo skin organ culture is a relevant experimental system to investigate signalling events following perturbations. As the identified proteins are components of pathways implicated in skin tumorigenesis, UV-exposed skin organ culture model could be used to investigate the effect on these pathways of NMSC cancer drug candidates. In addition, we found that phospho-HCK is induced upon UV exposure, producing a new candidate for future studies investigating its role in the skin response to UV and UV-induced carcinogenesis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

International Nuclear Information System (INIS)

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

2013-01-01

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

Interdisciplinary management of EGFR-inhibitor-induced skin reactions: a German expert opinion.

Science.gov (United States)

Potthoff, K; Hofheinz, R; Hassel, J C; Volkenandt, M; Lordick, F; Hartmann, J T; Karthaus, M; Riess, H; Lipp, H P; Hauschild, A; Trarbach, T; Wollenberg, A

2011-03-01

Anti-epidermal growth factor receptor treatment strategies, i.e. monoclonal antibodies such as cetuximab and panitumumab, or epidermal growth factor receptor (EGFR) small molecule tyrosine kinase inhibitors, such as erlotinib and gefitinib, have expanded the treatment options for different tumor types. Dermatologic toxic effects are the most common side-effects of EGFR inhibitor therapy. They can profoundly affect the patient's quality of life. The aim of this study was to provide interdisciplinary expert recommendations on how to treat patients with skin reactions undergoing anti-EGFR treatment. An expert panel from Germany with expertise in medical oncology, dermatology or clinical pharmacology was convened to develop expert recommendations based on published peer-reviewed literature. The expert recommendations for the state-of-the-art treatment of skin reactions induced by EGFR inhibitor therapy include recommendations for diagnostics and grading as well as grade-specific and stage-adapted treatment approaches and preventive measures. It was concluded that EGFR-inhibitor-related dermatologic reactions should always be treated combining basic care of the skin and a specific therapy adapted to stage and grade of skin reaction. For grade 2 and above, specific treatment recommendations for early- and later-stage skin reactions induced by EGFR-inhibitor therapy were proposed. This paper presents a German national expert opinion for the treatment of skin reactions in patients receiving EGFR inhibitor therapy.

ORIGINAL ARTICLES Warfarin-induced skin necrosis in HIV-1 ...

African Journals Online (AJOL)

F Bhaijee, H Wainwright, G Meintjes, R J Wilkinson, G Todd, E de Vries, D J Pepper. Warfarin-induced skin necrosis (WISN) is a rare complication of warfarin ..... first few days of warfarin therapy.2,11 Warfarin is a vitamin K antagonist and ...

Protective effect of Ocimum sanctum on 3-methylcholanthrene, 7,12-dimethylbenz(a)anthracene and aflatoxin B1 induced skin tumorigenesis in mice

Energy Technology Data Exchange (ETDEWEB)

Rastogi, Shipra; Shukla, Yogeshwer; Paul, Bhola N; Chowdhuri, D Kar; Khanna, Subhash K [Industrial Toxicology Research Centre, Mahatma Gandhi Marg, P.O. Box 80, Lucknow-226001 (India); Das, Mukul [Industrial Toxicology Research Centre, Mahatma Gandhi Marg, P.O. Box 80, Lucknow-226001 (India)

2007-11-01

A study on the protective effect of alcoholic extract of the leaves of Ocimum sanctum on 3-mthylcholanthrene (MCA), 7,12-dimethylbenzanthracene (DMBA) and aflatoxin B{sub 1} (AFB{sub 1}) induced skin tumorigenesis in a mouse model has been investigated. The study involved pretreatment of mice with the leaf extract prior to either MCA application or tetradecanoyl phorbol acetate (TPA) treatment in a two-stage tumor protocol viz a viz, DMBA/TPA and AFB1/TPA. The results of the present study indicate that the pretreatment with alcoholic extract of the leaves of O. sanctum decreased the number of tumors in MCA, DMBA/TPA and AFB1/TPA treated mice. The skin tumor induced animals pretreated with alcoholic extract led to a decrease in the expression of cutaneous {gamma}-glutamyl transpeptidase (GGT) and glutathione-S-transferase-P (GST-P) protein. The histopathological examination of skin tumors treated with leaf extract showed increased infiltration of polymorphonuclear, mononuclear and lymphocytic cells, decreased ornithine decarboxylase activity with concomitant enhancement of interleukin-1{beta} (IL-1{beta}) and tumor necrosis factor-{alpha} (TNF-{alpha}) in the serum, implying the in vivo antiproliferative and immunomodulatory activity of leaf extract. The decrease in cutaneous phase I enzymes and elevation of phase II enzymes in response to topical application of leaf extract prior to MCA, AFB1, DMBA/TPA and AFB1/TPA treatment indicate the possibility of impairment in reactive metabolite(s) formation and thereby reducing skin carcinogenicity. Furthermore, pretreatment of leaf extract in the carcinogen induced animals resulted in elevation of glutathione levels and decrease in lipid peroxidation along with heat shock protein expression, indicating a scavenging or antioxidant potential of the extract during chemical carcinogenesis. Thus it can be concluded that leaf extract of O. sanctum provides protection against chemical carcinogenesis in one or more of the

The impact of vehicle on the relative potency of skin-sensitizing chemicals in the local lymph node assay.

Science.gov (United States)

Jowsey, Ian R; Clapp, Catherine J; Safford, Bob; Gibbons, Ben T; Basketter, David A

2008-01-01

The identification and characterization of chemicals that possess skin-sensitizing potential are typically performed using predictive tests. However, human exposure to skin-sensitizing chemicals often occurs via a matrix (vehicle) that differs from that used in these tests. It is thus important to account for the potential impact of vehicle differences when undertaking quantitative risk assessment for skin sensitization. This is achieved through the application of a specific sensitization assessment factor (SAF), scaled between 1 and 10, when identifying an acceptable exposure level. The objective of the analysis described herein is to determine the impact of vehicle differences on local lymph node assay (LLNA) EC3 values (concentrations of test chemical required to provoke a 3-fold increase in lymph node cell proliferation). Initially, the inherent variability of the LLNA was investigated by examining the reproducibility of EC3 values for 14 chemicals that have been tested more than once in the same vehicle (4:1 acetone:olive oil, AOO). This analysis reveals that the variability in EC3 value for these chemicals following multiple assessments is LLNA using at least 2 of 15 different vehicles. These data demonstrate that often the variability in EC3 values observed for a given chemical in different vehicles is no greater than the 5-fold inherent variability observed when assessing a chemical in the same vehicle on multiple occasions. However, there are examples where EC3 values for a chemical differ by a factor of more than 10 between different vehicles. These observations were often associated with an apparent underestimation of potency (higher EC3 values) with predominantly aqueous vehicles or propylene glycol. These data underscore the need to consider vehicle effects in the context of skin-sensitization risk assessments.

Assessment of skin barrier function and biochemical changes of ex vivo human skin in response to physical and chemical barrier disruption.

Science.gov (United States)

Döge, Nadine; Avetisyan, Araks; Hadam, Sabrina; Pfannes, Eva Katharina Barbosa; Rancan, Fiorenza; Blume-Peytavi, Ulrike; Vogt, Annika

2017-07-01

Topical dermatotherapy is intended to be used on diseased skin. Novel drug delivery systems even address differences between intact and diseased skin underlining the need for pre-clinical assessment of different states of barrier disruption. Herein, we studied how short-term incubation in culture media compared to incubation in humidified chambers affects human skin barrier function and viability. On both models we assessed different types and intensities of physical and chemical barrier disruption methods with regard to structural integrity, biophysical parameters and cytokine levels. Tissue degeneration and proliferative activity limited the use of tissue cultures to 48h. Viability is better preserved in cultured tissue. Tape-stripping (50×TS) and 4h sodium lauryl sulfate (SLS) pre-treatment were identified as highly reproducible and effective procedures for barrier disruption. Transepidermal water loss (TEWL) values reproducibly increased with the intensity of disruption while sebum content and skin surface pH were of limited value. Interleukin (IL)-6/8 and various chemokines and proteases were increased in tape-stripped skin which was more pronounced in SLS-treated skin tissue extracts. Thus, albeit limited to 48h, cultured full-thickness skin maintained several barrier characteristics and responded to different intensities of barrier disruption. Potentially, these models can be used to assess pre-clinically the efficacy and penetration of anti-inflammatory compounds. Copyright © 2016 Elsevier B.V. All rights reserved.

Ultra-violet B (UVB)-induced skin cell death occurs through a cyclophilin D intrinsic signaling pathway

International Nuclear Information System (INIS)

Ji, Chao; Yang, Bo; Yang, Zhi; Tu, Ying; Yang, Yan-li; He, Li; Bi, Zhi-Gang

2012-01-01

Highlights: ► UVB radiated skin keratinocytes show cyclophilin D (Cyp-D) upregulation. ► NAC inhibits UVB induced Cyp-D expression, while H 2 O 2 facilitates it. ► Cyp-D-deficient cells are significantly less susceptible to UVB induced cell death. ► Over-expression of Cyp-D causes spontaneous keratinocytes cell death. -- Abstract: UVB-induced skin cell damage involves the opening of mitochondrial permeability transition pore (mPTP), which leads to both apoptotic and necrotic cell death. Cyclophilin D (Cyp-D) translocation to the inner membrane of mitochondrion acts as a key component to open the mPTP. Our Western-Blot results in primary cultured human skin keratinocytes and in HaCaT cell line demonstrated that UVB radiation and hydrogen peroxide (H 2 O 2 ) induced Cyp-D expression, which was inhibited by anti-oxidant N-acetyl cysteine (NAC). We created a stable Cyp-D deficiency skin keratinocytes by expressing Cyp-D-shRNA through lentiviral infection. Cyp-D-deficient cells were significantly less susceptible than their counterparts to UVB- or H 2 O 2 -induced cell death. Further, cyclosporine A (Cs-A), a Cyp-D inhibitor, inhibited UVB- or H 2 O 2 -induced keratinocytes cell death. Reversely, over-expression of Cyp-D in primary keratinocytes caused spontaneous keratinocytes cell death. These results suggest Cyp-D’s critical role in UVB/oxidative stress-induced skin cell death.

The efficacy of Pistacia Terebinthus soap in the treatment of cetuximab-induced skin toxicity.

Science.gov (United States)

Tastekin, Didem; Tambas, Makbule; Kilic, Kemal; Erturk, Kayhan; Arslan, Deniz

2014-12-01

This open-labeled phase II, efficacy-finding study evaluated the efficiency and safety of Pistacia terebinthus soap in metastatic colorectal cancer patients who developed cetuximab induced skin toxicity. Patients who received cetuximab plus chemotherapy and developed Grade 2 or 3 skin toxicity were treated twice daily with a soap made of oil extracted from Pistacia terebinthus. During treatment, no topical or oral antibiotics, corticosteroids or other moisturizers were used. Patients were examined 1 week later and their photographs were taken. Fifteen mCRC patients who developed skin toxicity while receiving first-line CTX in combination with chemotherapy were included into the study. Eight patients were male and the median age was 58 (25-70). Sixty percent of the patients (n:9) had Grade 3 skin toxicity. Complete response rates in patients with Grade 2 and Grade 3 skin toxicities were 100 and 33%, respectively. In the remaining patients with Grade 3 toxicity the skin toxicity regressed to Grade 1. The objective response rate was 100%, and no delay, dose reduction or discontinuation of CTX treatment due to skin toxicity was necessary. Skin toxicity reoccurred in all patients when patients stopped administering the soap and therefore they used it throughout the cetuximab treatment. Pistacia terebinthus soap seemed to be used safely and effectively in the treatment of skin toxicity induced by Cetuximab.

Chemical Detection Based on Adsorption-Induced and Photo-Induced Stresses in MEMS Devices

Energy Technology Data Exchange (ETDEWEB)

Datskos, P.G.

1999-04-05

Recently there has been an increasing demand to perform real-time in-situ chemical detection of hazardous materials, contraband chemicals, and explosive chemicals. Currently, real-time chemical detection requires rather large analytical instrumentation that are expensive and complicated to use. The advent of inexpensive mass produced MEMS (micro-electromechanical systems) devices opened-up new possibilities for chemical detection. For example, microcantilevers were found to respond to chemical stimuli by undergoing changes in their bending and resonance frequency even when a small number of molecules adsorb on their surface. In our present studies, we extended this concept by studying changes in both the adsorption-induced stress and photo-induced stress as target chemicals adsorb on the surface of microcantilevers. For example, microcantilevers that have adsorbed molecules will undergo photo-induced bending that depends on the number of absorbed molecules on the surface. However, microcantilevers that have undergone photo-induced bending will adsorb molecules on their surfaces in a distinctly different way. Depending on the photon wavelength and microcantilever material, the microcantilever can be made to bend by expanding or contracting the irradiated surface. This is important in cases where the photo-induced stresses can be used to counter any adsorption-induced stresses and increase the dynamic range. Coating the surface of the microstructure with a different material can provide chemical specificity for the target chemicals. However, by selecting appropriate photon wavelengths we can change the chemical selectivity due to the introduction of new surface states in the MEMS device. We will present and discuss our results on the use of adsorption-induced and photo-induced bending of microcantilevers for chemical detection.

ADA-07 Suppresses Solar Ultraviolet-Induced Skin Carcinogenesis by Directly Inhibiting TOPK.

Science.gov (United States)

Gao, Ge; Zhang, Tianshun; Wang, Qiushi; Reddy, Kanamata; Chen, Hanyong; Yao, Ke; Wang, Keke; Roh, Eunmiri; Zykova, Tatyana; Ma, Weiya; Ryu, Joohyun; Curiel-Lewandrowski, Clara; Alberts, David; Dickinson, Sally E; Bode, Ann M; Xing, Ying; Dong, Zigang

2017-09-01

Cumulative exposure to solar ultraviolet (SUV) irradiation is regarded as the major etiologic factor in the development of skin cancer. The activation of the MAPK cascades occurs rapidly and is vital in the regulation of SUV-induced cellular responses. The T-LAK cell-originated protein kinase (TOPK), an upstream activator of MAPKs, is heavily involved in inflammation, DNA damage, and tumor development. However, the chemopreventive and therapeutic effects of specific TOPK inhibitors in SUV-induced skin cancer have not yet been elucidated. In the current study, ADA-07, a novel TOPK inhibitor, was synthesized and characterized. Pull-down assay results, ATP competition, and in vitro kinase assay data revealed that ADA-07 interacted with TOPK at the ATP-binding pocket and inhibited its kinase activity. Western blot analysis showed that ADA-07 suppressed SUV-induced phosphorylation of ERK1/2, p38, and JNKs and subsequently inhibited AP-1 activity. Importantly, topical treatment with ADA-07 dramatically attenuated tumor incidence, multiplicity, and volume in SKH-1 hairless mice exposed to chronic SUV. Our findings suggest that ADA-07 is a promising chemopreventive or potential therapeutic agent against SUV-induced skin carcinogenesis that acts by specifically targeting TOPK. Mol Cancer Ther; 16(9); 1843-54. ©2017 AACR . ©2017 American Association for Cancer Research.

Ultra-violet B (UVB)-induced skin cell death occurs through a cyclophilin D intrinsic signaling pathway.

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Ji, Chao; Yang, Bo; Yang, Zhi; Tu, Ying; Yang, Yan-li; He, Li; Bi, Zhi-Gang

2012-09-07

UVB-induced skin cell damage involves the opening of mitochondrial permeability transition pore (mPTP), which leads to both apoptotic and necrotic cell death. Cyclophilin D (Cyp-D) translocation to the inner membrane of mitochondrion acts as a key component to open the mPTP. Our Western-Blot results in primary cultured human skin keratinocytes and in HaCaT cell line demonstrated that UVB radiation and hydrogen peroxide (H(2)O(2)) induced Cyp-D expression, which was inhibited by anti-oxidant N-acetyl cysteine (NAC). We created a stable Cyp-D deficiency skin keratinocytes by expressing Cyp-D-shRNA through lentiviral infection. Cyp-D-deficient cells were significantly less susceptible than their counterparts to UVB- or H(2)O(2)-induced cell death. Further, cyclosporine A (Cs-A), a Cyp-D inhibitor, inhibited UVB- or H(2)O(2)-induced keratinocytes cell death. Reversely, over-expression of Cyp-D in primary keratinocytes caused spontaneous keratinocytes cell death. These results suggest Cyp-D's critical role in UVB/oxidative stress-induced skin cell death. Copyright © 2012 Elsevier Inc. All rights reserved.

Helicobacter pylori-induced premature senescence of extragastric cells may contribute to chronic skin diseases.

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Lewinska, Anna; Wnuk, Maciej

2017-04-01

Helicobacter pylori, one of the most frequently observed bacterium in the human intestinal flora, has been widely studied since Marshall and Warren documented a link between the presence of H. pylori in the gastrointestinal tract and gastritis and gastric ulcers. Interestingly, H. pylori has also been found in several other epithelial tissues, including the eyes, ears, nose and skin that may have direct or indirect effects on host physiology and may contribute to extragastric diseases, e.g. chronic skin diseases. More recently, it has been shown that H. pylori cytotoxin CagA expression induces cellular senescence of human gastric nonpolarized epithelial cells that may lead to gastrointestinal disorders and systemic inflammation. Here, we hypothesize that also chronic skin diseases may be promoted by stress-induced premature senescence (SIPS) of skin cells, namely fibroblasts and keratinocytes, stimulated with H. pylori cytotoxins. Future studies involving cell culture models and clinical specimens are needed to verify the involvement of H. pylori in SIPS-based chronic skin diseases.

Kaempferol targets RSK2 and MSK1 to suppress ultraviolet radiation-induced skin cancer

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Langfald, Alyssa; Yang, Ge; Zhang, Yi; Yu, Dong Hoon; Kim, Myoung Ok; Lee, Mee-Hyun; Li, Haitao; Bae, Ki Beom; Kim, Hong-Gyum; Ma, Wei-Ya; Bode, Ann M.; Dong, Ziming; Dong, Zigang

2014-01-01

Solar ultraviolet (SUV) irradiation is a major factor in skin carcinogenesis, the most common form of cancer in the USA. The mitogen-activated protein (MAP) kinase cascades are activated by SUV irradiation. The 90 kDa ribosomal S6 kinase (RSK) and mitogen and stress activated protein kinase (MSK) proteins constitute a family of protein kinases that mediate signal transduction downstream of the MAP kinase cascades. In this study, phosphorylation of RSK and MSK1 was up-regulated in human squamous cell carcinoma (SCC) and solar UV-treated mouse skin. Kaempferol, a natural flavonol, found in tea, broccoli, grapes, apples and other plant sources, is known to have anticancer activity, but its mechanisms and direct target(s) in cancer chemoprevention are unclear. Kinase array results revealed that kaempferol inhibited RSK2 and MSK1. Pull-down assay results, ATP competition and in vitro kinase assay data revealed that kaempferol interacts with RSK2 and MSK1 at the ATP-binding pocket and inhibits their respective kinase activities. Mechanistic investigations showed that kaempferol suppresses RSK2 and MSK1 kinase activities to attenuate solar UV-induced phosphorylation of CREB and histone H3 in mouse skin cells. Kaempferol was a potent inhibitor of solar UV-induced mouse skin carcinogenesis. Further analysis showed that skin from the kaempferol-treated group exhibited a substantial reduction in solar UV-induced phosphorylation of cAMP response element-binding protein (CREB), c-Fos and histone H3. Overall, our results identify kaempferol as a safe and novel chemopreventive agent against solar UV-induced skin carcinogenesis that acts by targeting RSK2 and MSK1. PMID:24994661

Kaempferol targets RSK2 and MSK1 to suppress UV radiation-induced skin cancer.

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Yao, Ke; Chen, Hanyong; Liu, Kangdong; Langfald, Alyssa; Yang, Ge; Zhang, Yi; Yu, Dong Hoon; Kim, Myoung Ok; Lee, Mee-Hyun; Li, Haitao; Bae, Ki Beom; Kim, Hong-Gyum; Ma, Wei-Ya; Bode, Ann M; Dong, Ziming; Dong, Zigang

2014-09-01

Solar UV (SUV) irradiation is a major factor in skin carcinogenesis, the most common form of cancer in the United States. The MAPK cascades are activated by SUV irradiation. The 90 kDa ribosomal S6 kinase (RSK) and mitogen and stress-activated protein kinase (MSK) proteins constitute a family of protein kinases that mediate signal transduction downstream of the MAPK cascades. In this study, phosphorylation of RSK and MSK1 was upregulated in human squamous cell carcinoma (SCC) and SUV-treated mouse skin. Kaempferol, a natural flavonol, found in tea, broccoli, grapes, apples, and other plant sources, is known to have anticancer activity, but its mechanisms and direct target(s) in cancer chemoprevention are unclear. Kinase array results revealed that kaempferol inhibited RSK2 and MSK1. Pull-down assay results, ATP competition, and in vitro kinase assay data revealed that kaempferol interacts with RSK2 and MSK1 at the ATP-binding pocket and inhibits their respective kinase activities. Mechanistic investigations showed that kaempferol suppresses RSK2 and MSK1 kinase activities to attenuate SUV-induced phosphorylation of cAMP-responsive element binding protein (CREB) and histone H3 in mouse skin cells. Kaempferol was a potent inhibitor of SUV-induced mouse skin carcinogenesis. Further analysis showed that skin from the kaempferol-treated group exhibited a substantial reduction in SUV-induced phosphorylation of CREB, c-Fos, and histone H3. Overall, our results identify kaempferol as a safe and novel chemopreventive agent against SUV-induced skin carcinogenesis that acts by targeting RSK2 and MSK1. ©2014 American Association for Cancer Research.

Skin protection against UVA-induced iron damage by multiantioxidants and iron chelating drugs/prodrugs.

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Reelfs, Olivier; Eggleston, Ian M; Pourzand, Charareh

2010-03-01

In humans, prolonged sunlight exposure is associated with various pathological states. The continuing drive to develop improved skin protection involves not only approaches to reduce DNA damage by solar ultraviolet B (UVB) but also the development of methodologies to provide protection against ultraviolet A (UVA), the oxidising component of sunlight. Furthermore identification of specific cellular events following ultraviolet (UV) irradiation is likely to provide clues as to the mechanism of the development of resulting pathologies and therefore strategies for protection. Our discovery that UVA radiation, leads to an immediate measurable increase in 'labile' iron in human skin fibroblasts and keratinocytes provides a new insight into UVA-induced skin damage, since iron is a catalyst of biological oxidations. The main purpose of this overview is to bring together some of the new findings related to mechanisms underlying UVA-induced iron release and to discuss novel approaches based on the use of multiantioxidants and light-activated caged-iron chelators for efficient protection of skin cells against UVA-induced iron damage.

EPR persistence measurements of UV-induced melanin free radicals in whole skin

International Nuclear Information System (INIS)

Collins, B.; Poehler, T.O.; Bryden, W.A.

1995-01-01

Electron paramagnetic resonance is used to detect the formation of free radicals caused by exposure to ultraviolet radiation in chemically untreated rabbit skin. A fast jump in EPR signal level, occurring over a few seconds, is observed immediately after a skin sample is exposed to UV. This is followed by a slower increase toward an elevated steady-state signal over a period of hours as the skin is continuously exposed to a UV light source. Upon cessation of UV light exposure, EPR signal levels undergo an abrupt drop followed by a slower decay toward natural levels. Elevated free radical concentrations following UV exposure are found to persist for several hours in whole skin. These results are consistent with time resolved EPR measurements of photoinduced radicals in various natural melanins. (Author)

Evaluation of efficacy of chemical peeling with glycolic acid in hyperpigmentation disorders of the skin

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Supriya P Deshmukh

2012-01-01

Full Text Available Background : Chemical peeling entails application of chemical agents to the skin causing a controlled chemical burn, thereby achieving improved texture and quality of skin. Aim: To evaluate the efficacy of glycolic acid in melasma and other causes of hyperpigmentation. Materials and Methods: A total of 20 patients were included in the study. After adequate priming, application of glycolic acid in various concentrations in biweekly interval for a period of 16 weeks was done. Post-treatment photographs were taken and were subjected to analysis. Results: Melasma constituted 11 patients and hyperpigmentation, ie, post acne marks and freckles due to sun exposure accounted nine patients. Complete resolution of melasma was possible only in one (9% patient and good improvement in four (36.3%, whereas five (45.5% patients showed fair improvement. In cases of hyperpigmentation, three (33% patients showed excellent improvement, one (11% showed good improvement, and five (55.5% patients showed fair improvement. The patients of melasma took an average of 7.33 number of peels to show improvement and those of hyperpigmentation took 4.2 peels. Conclusions: Melasma shows fair to good improvement and requires more number of peels as compared to other causes of hyperpigmentation in skin. Postinflammatory pigmentation shows excellent improvement in the majority of patients.

Maximum skin hyperaemia induced by local heating: possible mechanisms.

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Gooding, Kim M; Hannemann, Michael M; Tooke, John E; Clough, Geraldine F; Shore, Angela C

2006-01-01

Maximum skin hyperaemia (MH) induced by heating skin to > or = 42 degrees C is impaired in individuals at risk of diabetes and cardiovascular disease. Interpretation of these findings is hampered by the lack of clarity of the mechanisms involved in the attainment of MH. MH was achieved by local heating of skin to 42-43 degrees C for 30 min, and assessed by laser Doppler fluximetry. Using double-blind, randomized, placebo-controlled crossover study designs, the roles of prostaglandins were investigated by inhibiting their production with aspirin and histamine, with the H1 receptor antagonist cetirizine. The nitric oxide (NO) pathway was blocked by the NO synthase inhibitor, NG-nitro-L-arginine methyl esther (L-NAME), and enhanced by sildenafil (prevents breakdown of cGMP). MH was not altered by aspirin, cetirizine or sildenafil, but was reduced by L-NAME: median placebo 4.48 V (25th, 75th centiles: 3.71, 4.70) versus L-NAME 3.25 V (3.10, 3.80) (p = 0.008, Wilcoxon signed rank test). Inhibition of NO production (L-NAME) resulted in a more rapid reduction in hyperaemia after heating (p = 0.011), whereas hyperaemia was prolonged in the presence of sildenafil (p = 0.003). The increase in skin blood flow was largely confined to the directly heated area, suggesting that the role of heat-induced activation of the axon reflex was small. NO, but not prostaglandins, histamine or an axon reflex, contributes to the increase in blood flow on heating and NO is also a component of the resolution of MH after heating. Copyright 2006 S. Karger AG, Basel.

Surfactant-induced skin irritation and skin repair: evaluation of a cumulative human irritation model by noninvasive techniques.

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Wilhelm, K P; Freitag, G; Wolff, H H

1994-12-01

Although surfactant-induced acute irritant dermatitis has been extensively studied, our understanding about the induction and repair of the clinically more relevant chronic form is limited. Our purpose was to investigate qualitative and quantitative differences in surfactant-induced irritant skin reactions from cumulative exposure to structurally unrelated surfactants and to compare the maximal irritant responses from this model with corresponding reactions noted in a previously reported acute irritation model. Sodium lauryl sulfate (SLS), dodecyl trimethyl ammonium bromide (DTAB), and potassium soap were the model irritants. Surfactant solutions (7.5%) were applied for 20 minutes daily (for 8 consecutive days excluding the weekend) to the volar aspect of the forearm of 11 volunteers. Irritant reactions were repeatedly assessed until complete healing was indicated by visual assessment and by measurements of transepidermal water loss (TEWL), erythema (skin color reflectance), and stratum corneum hydration (electrical capacitance). Maximum irritant responses were compared with corresponding reactions from an acute irritation model. TEWL was increased by SLS and DTAB to the same extent, but erythema was significantly higher in DTAB-treated skin. Skin dryness, as demonstrated by decreased capacitance values and increased scores for scaling and fissuring, was significantly more pronounced than in an acute irritation model for SLS and DTAB, although no difference was detected between the two surfactants. Potassium soap led to a slight increase in TEWL, whereas the remaining features were not significantly changed. This chronic irritation model appears to represent the clinical situation of irritant contact dermatitis with pronounced skin dryness more closely than the acute irritation model. The present study confirms that an extended time is needed for complete healing of irritant skin reactions. We also demonstrated that the evaluation of the irritation potential of

Investigations of antioxidant-mediated protection and mitigation of radiation-induced DNA damage and lipid peroxidation in murine skin.

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Jelveh, Salomeh; Kaspler, Pavel; Bhogal, Nirmal; Mahmood, Javed; Lindsay, Patricia E; Okunieff, Paul; Doctrow, Susan R; Bristow, Robert G; Hill, Richard P

2013-08-01

Radioprotection and mitigation effects of the antioxidants, Eukarion (EUK)-207, curcumin, and the curcumin analogs D12 and D68, on radiation-induced DNA damage or lipid peroxidation in murine skin were investigated. These antioxidants were studied because they have been previously reported to protect or mitigate against radiation-induced skin reactions. DNA damage was assessed using two different assays. A cytokinesis-blocked micronucleus (MN) assay was performed on primary skin fibroblasts harvested from the skin of C3H/HeJ male mice 1 day, 1 week and 4 weeks after 5 Gy or 10 Gy irradiation. Local skin or whole body irradiation (100 kVp X-rays or caesium (Cs)-137 γ-rays respectively) was performed. DNA damage was further quantified in keratinocytes by immunofluorescence staining of γ-histone 2AX (γ-H2AX) foci in formalin-fixed skin harvested 1 hour or 1 day post-whole body irradiation. Radiation-induced lipid peroxidation in the skin was investigated at the same time points as the MN assay by measuring malondialdehyde (MDA) with a Thiobarbituric acid reactive substances (TBARS) assay. None of the studied antioxidants showed significant mitigation of skin DNA damage induced by local irradiation. However, when EUK-207 or curcumin were delivered before irradiation they provided some protection against DNA damage. In contrast, all the studied antioxidants demonstrated significant mitigating and protecting effects on radiation-induced lipid peroxidation at one or more of the three time points after local skin irradiation. Our results show no evidence for mitigation of DNA damage by the antioxidants studied in contrast to mitigation of lipid peroxidation. Since these agents have been reported to mitigate skin reactions following irradiation, the data suggest that changes in lipid peroxidation levels in skin may reflect developing skin reactions better than residual post-irradiation DNA damage in skin cells. Further direct comparison studies are required to confirm

Photoreactivation of ultraviolet radiation-induced pyrimidine dimers in neonatal BALB/c mouse skin

International Nuclear Information System (INIS)

Ananthaswamy, H.N.; Fisher, M.S.

1981-01-01

The numbers of ultraviolet light (uv)-induced pyrimidine dimers in the DNA of neonatal BALB/c mouse skin were measured by assessing the sensitivity of the DNA to Micrococcus luteus uv endonuclease. Irradiation of neonatal BALB/c mice with FS40 sunlamps caused a dose-dependent induction of endonuclease-sensitive sites (pyrimidine dimers) in DNA extracted from back skin. Exposure of these uv-irradiated neonatal mice to photoreactivating (PR) light (cool white fluorescent lamp and incandescent lamp) caused a reduction in the number of pyrimidine dimers in the DNA, as revealed by a shift in low-molecular-weight DNA to high-molecular-weight DNA. In contrast, DNA profiles of the skin of either uv-irradiated mice or uv-irradiated mice kept in the dark for the same duration as those exposed to PR light did not show a loss of uv-induced endonuclease-sensitive sites. Furthermore, reversing the order of treatment, i.e., administering PR light first and then uv, did not produce a reduction in pyrimidine dimers. These results demonstrate that PR or uv-induced pyrimidine dimers occurs in neonatal BALB/c mouse skin. The optimal wavelength range for in vivo PR appears to be in the visible region of the spectrum (greater than 400 nm). Although dimer formation could be detected in both dermis and epidermis, PR occurred only in the dermis. Furthermore, the PR phenomenon could not be detected in the skin of adult mice from the same inbred strain

Laser-induced fluorescence for the detection of esophageal and skin cancer

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Vo-Dinh, Tuan; Panjehpour, Masoud; Overholt, Bergein F.; Julius, Clark E.; Overholt, Suzanne; Phan, Mary N.

2003-07-01

Laser-induced fluorescence (LIF) is used for in-vivo cancer diagnosis of the esophagus and skin cancer. For esophageal measurements a fiberoptic probe inserted through an endoscope was used. Autofluorescence of normal and malignant tissues were measured directly on patient skin without requiring an endoscope. Measurement of the fluorescence signal from the tissue was performed using laser excitation at 410 nm. The methodology was applied to differentiate normal and malignant tumors of the esophagus and malignant skin lesions. The results of this LIF approach were compared with histopathology results of the biopsy samples and indicated excellent agreement in the classification of normal and malignant tumors for the samples investigated.

Ultra-violet B (UVB)-induced skin cell death occurs through a cyclophilin D intrinsic signaling pathway

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Ji, Chao [Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210024, Jiangsu (China); Yang, Bo [Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040 (China); Yang, Zhi; Tu, Ying [Department of Dermatology, The First Affiliated Hospital of Kunming Medical University, Yunnan Provincial Institute of Dermatology, Kunming 650032, Yunnan (China); Yang, Yan-li [Department of Otorhinolaryngology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210024, Jiangsu (China); He, Li, E-mail: heli2662@yahoo.com.cn [Department of Otorhinolaryngology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210024, Jiangsu (China); Bi, Zhi-Gang, E-mail: eltonbibenqhospital@yahoo.com.cn [Department of Dermatology, BenQ Medical Center, Nanjing Medical University, Nanjing 210019, Jiangsu (China)

2012-09-07

Highlights: Black-Right-Pointing-Pointer UVB radiated skin keratinocytes show cyclophilin D (Cyp-D) upregulation. Black-Right-Pointing-Pointer NAC inhibits UVB induced Cyp-D expression, while H{sub 2}O{sub 2} facilitates it. Black-Right-Pointing-Pointer Cyp-D-deficient cells are significantly less susceptible to UVB induced cell death. Black-Right-Pointing-Pointer Over-expression of Cyp-D causes spontaneous keratinocytes cell death. -- Abstract: UVB-induced skin cell damage involves the opening of mitochondrial permeability transition pore (mPTP), which leads to both apoptotic and necrotic cell death. Cyclophilin D (Cyp-D) translocation to the inner membrane of mitochondrion acts as a key component to open the mPTP. Our Western-Blot results in primary cultured human skin keratinocytes and in HaCaT cell line demonstrated that UVB radiation and hydrogen peroxide (H{sub 2}O{sub 2}) induced Cyp-D expression, which was inhibited by anti-oxidant N-acetyl cysteine (NAC). We created a stable Cyp-D deficiency skin keratinocytes by expressing Cyp-D-shRNA through lentiviral infection. Cyp-D-deficient cells were significantly less susceptible than their counterparts to UVB- or H{sub 2}O{sub 2}-induced cell death. Further, cyclosporine A (Cs-A), a Cyp-D inhibitor, inhibited UVB- or H{sub 2}O{sub 2}-induced keratinocytes cell death. Reversely, over-expression of Cyp-D in primary keratinocytes caused spontaneous keratinocytes cell death. These results suggest Cyp-D's critical role in UVB/oxidative stress-induced skin cell death.

Influence of drying temperature on the chemical constituents of jaboticaba (Plinia Jaboticaba (Vell. Berg skin

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Ana Paula de C. Alves

2014-09-01

Full Text Available Jaboticaba is a fruit native to Brazil. Its skin represents up to 43% of the fruit and contains high levels of fiber, minerals and phenolic compounds. The use of the skin waste adds value to the fruit. However, one of the drawbacks of skin storage is the high water content, which requires drying processes to preserve the skin without leading to the loss of nutrients and antioxidants. The influence of different drying temperatures on the levels of nutrients and antioxidants was investigated. Jaboticaba (Plinia jaboticaba (Vell. Berg, genotype Sabará skins were lyophilized or dried at three temperatures (30, 45, and 60ºC, using food dryers. The skins were then ground, stored (protected from light and subjected to analysis of proximate composition, vitamin C, phytate, polyphenols, anthocyanins and antioxidant activity. The drying process had little effect on the proximate composition of the flour, presenting significant difference only for crude protein, fiber and non-nitrogenous extract. The greatest preservation of chemical constituents occurs in the lyophilized jaboticaba skins. Among the drying temperatures tested, however, the skins dried at 45 and60°C had more highly preserved nutritional substances and antioxidants.

Solar ultraviolet irradiation induces decorin degradation in human skin likely via neutrophil elastase.

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Li, Yong; Xia, Wei; Liu, Ying; Remmer, Henriette A; Voorhees, John; Fisher, Gary J

2013-01-01

Exposure of human skin to solar ultraviolet (UV) irradiation induces matrix metalloproteinase-1 (MMP-1) activity, which degrades type I collagen fibrils. Type I collagen is the most abundant protein in skin and constitutes the majority of skin connective tissue (dermis). Degradation of collagen fibrils impairs the structure and function of skin that characterize skin aging. Decorin is the predominant proteoglycan in human dermis. In model systems, decorin binds to and protects type I collagen fibrils from proteolytic degradation by enzymes such as MMP-1. Little is known regarding alterations of decorin in response to UV irradiation. We found that solar-simulated UV irradiation of human skin in vivo stimulated substantial decorin degradation, with kinetics similar to infiltration of polymorphonuclear (PMN) cells. Proteases that were released from isolated PMN cells degraded decorin in vitro. A highly selective inhibitor of neutrophil elastase blocked decorin breakdown by proteases released from PMN cells. Furthermore, purified neutrophil elastase cleaved decorin in vitro and generated fragments with similar molecular weights as those resulting from protease activity released from PMN cells, and as observed in UV-irradiated human skin. Cleavage of decorin by neutrophil elastase significantly augmented fragmentation of type I collagen fibrils by MMP-1. Taken together, these data indicate that PMN cell proteases, especially neutrophil elastase, degrade decorin, and this degradation renders collagen fibrils more susceptible to MMP-1 cleavage. These data identify decorin degradation and neutrophil elastase as potential therapeutic targets for mitigating sun exposure-induced collagen fibril degradation in human skin.

Skin tightening.

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Woolery-Lloyd, Heather; Kammer, Jenna N

2011-01-01

Skin tightening describes the treatment of skin laxity via radiofrequency (RF), ultrasound, or light-based devices. Skin laxity on the face is manifested by progressive loss of skin elasticity, loosening of the connective tissue framework, and deepening of skin folds. This results in prominence of submandibular and submental tissues. Genetic factors (chronological aging) and extrinsic factors (ultraviolet radiation) both contribute to skin laxity. There are many RF, ultrasound, and light-based devices directed at treating skin laxity. All of these devices target and heat the dermis to induce collagen contraction. Heating of the dermis causes collagen denaturation and immediate collagen contraction in addition to long-term collagen remodeling. Via RF, light, or ultrasound, these skin tightening devices deliver heat to the dermis to create new collagen and induce skin tightening. This chapter will provide an overview of the various skin tightening devices. Copyright © 2011 S. Karger AG, Basel.

Expression of telomerase reverse transcriptase in radiation-induced chronic human skin ulcer

International Nuclear Information System (INIS)

Zhao Po; Li Zhijun; Lu Yali; Zhong Mei; Gu Qingyang; Wang Dewen

2001-01-01

Objective: To investigate the expression of the catalytic subunit of telomerase, telomerase reverse transcriptase (TRT) and the possible relationship between the TRT and cancer transformation or poor healing in radiation-induced chronic ulcer of human skin. Methods: Rabbit antibody against human TRT and SP immunohistochemical method were used to detect TRT expression in 24 cases of formalin-fixed, paraffin-embed human skin chronic ulcer tissues induced by radiation, 5 cases of normal skin, 2 of burned skin, and 8 of carcinoma. Results: The positive rate for TRT was 58.3%(14/24) in chronic radiation ulcers, of which the strongly positive rate was 41.7%(10/24) and the weakly positive 16.7%(4/24), 0% in normal (0/5) and burned skin (0/2), and 100% in carcinoma (8/8). The strongly positive expression of TRT was observed almost always in the cytoplasm and nucleus of squamous epithelial cells of proliferative epidermis but the negative and partly weakly positive expression in the smooth muscles, endothelia of small blood vessels and capillaries, and fibroblasts. Chronic inflammtory cells, plasmacytes and lymphocytes also showed weakly positive for TRT. Conclusion: TRT expression could be involved in the malignant transformation of chronic radiation ulcer into squamous carcinoma, and in the poor healing caused by sclerosis of small blood vessels and lack of granulation tissue consisting of capillaries and fibroblasts

Overexpression of p53, MDM2 proteins in some atr radiation-induced skin ulcers

International Nuclear Information System (INIS)

Gu Qingyang; Gao Yabing; Wang Dewen; Cui Yufang; Zhao Po; Yang Zhixiang; Zhou Jie

2000-01-01

An animal model of radiation-induced skin ulcer was set up with 140 rats, which were locally irradiated with 35-55 Gy γ-rays. The pathological changes were observed for 1 year. Immunohistochemical studies were performed in 72 rat radiation skin ulcer specimens using anti-p53 and anti-MDM2 proteins polyclonal antibodies. The results showed that the positive rate for overexpression of p53 protein was 9.7%, and for that of MDM2 was 19.4%. The overexpression of p53 was mainly seen in the nuclei of activated squamous epithelial cells, and in fibroblasts, endotheliocytes in deeper part of the skin ulcers. The overexpression of MDM2 had the same localizations. It is suggested that the changes of p53 and MDM2, genes and proteins, may be related to the cancer transformation and poor healing of radiation-induced skin ulcers

Chemical Characterization of Lipophilic Constituents in the Skin of Migratory Adult Sea Lamprey from the Great Lakes Region.

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Amila A Dissanayake

Full Text Available The sea lamprey (Petromzons marinus is an invasive ectoparasite of large-bodied fishes that adversely affects the fishing industry and ecology of the Laurentian Great Lakes. Lipid content in the whole sea lamprey and muscles, liver and kidney of metamorphosing larval stages has been reported. Similarly, the fatty acid profile of the rope tissues of sexually-mature male sea lampreys has also been reported. The average body weight of a sub-adult migratory sea lamprey is 250 g, which includes 14.4% skin (36 g. Our preliminary extraction data of an adult sea lamprey skin revealed that it contained approximately 8.5% of lipophilic compounds. Lamprey skin is home to a naturally aversive compound (an alarm cue that is being developed into a repellent for use in pest management. As part of an ongoing investigation to identify the chemical structure of the sea lamprey alarm cue, we extracted the skin with water and methanol, respectively. The methanolic extract (1.55% contained exclusively lipophilic compounds and did not include the alarm cue. We chemically characterized all compounds present in the methanolic extract as cholesterol esters (CE, tri- and di-glycerides (TG and DG, cholesterol, free fatty acids (FFA and minor amounts of plasticizers. The free fatty acids fraction was composed of saturated (41.8%, monounsaturated (40.7% and polyunsaturated (17.4% fatty acids, respectively. The plasticizers characterized were phthalate and benzoate and found to be 0.95 mg and 2.54 mg, respectively, per adult sea lamprey skin. This is the first report of the chemical characterization of all the lipophilic constituents in the skin of sub-adult migratory sea lamprey. The CEs isolated and characterized from sea lamprey skin are also for the first time.

l-Ergothioneine Protects Skin Cells against UV-Induced Damage—A Preliminary Study

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Karolina Bazela

2014-03-01

Full Text Available Many changes related to aging at the cellular level may be due to the physiological condition of mitochondria. One of the most common types of damage of mtDNA is the so-called “common deletion” referring to a deletion of 4977 base pairs. In the skin cells this phenomenon probably is caused by oxidative damage of mtDNA induced by UV. The present study was aimed at evaluating the effect of the antioxidant l-ergothioneine on UV-induced damage in skin cells. The effect of l-ergothioneine on the reduced glutathione level was studied. The presence of the “common deletion” in human fibroblasts irradiated with UVA and treated with l-ergothioneine was evaluated by a polymerase chain reaction. We have demonstrated that l-ergothioneine enhanced the level of reduced glutathione and protected cells from the induction of a photoaging-associated mtDNA “common deletion”. In view of our results, l-ergothioneine could be an effective skin care and anti-photoaging ingredient.

Protection against UVB-induced oxidative stress in human skin cells and skin models by methionine sulfoxide reductase A.

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Pelle, Edward; Maes, Daniel; Huang, Xi; Frenkel, Krystyna; Pernodet, Nadine; Yarosh, Daniel B; Zhang, Qi

2012-01-01

Environmental trauma to human skin can lead to oxidative damage of proteins and affect their activity and structure. When methionine becomes oxidized to its sulfoxide form, methionine sulfoxide reductase A (MSRA) reduces it back to methionine. We report here the increase in MSRA in normal human epidermal keratinocytes (NHEK) after ultraviolet B (UVB) radiation, as well as the reduction in hydrogen peroxide levels in NHEK pre-treated with MSRA after exposure. Further, when NHEK were pre-treated with a non-cytotoxic pentapeptide containing methionine sulfoxide (metSO), MSRA expression increased by 18.2%. Additionally, when the media of skin models were supplemented with the metSO pentapeptide and then exposed to UVB, a 31.1% reduction in sunburn cells was evident. We conclude that the presence of MSRA or an externally applied peptide reduces oxidative damage in NHEK and skin models and that MSRA contributes to the protection of proteins against UVB-induced damage in skin.

Oral Administration of Vanillin Improves Imiquimod-Induced Psoriatic Skin Inflammation in Mice.

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Cheng, Hui-Man; Chen, Feng-Yuan; Li, Chia-Cheng; Lo, Hsin-Yi; Liao, Yi-Fang; Ho, Tin-Yun; Hsiang, Chien-Yun

2017-11-29

Vanillin is one of the most widely used flavoring products worldwide. Psoriasis is a chronic inflammatory skin disorder. The interleukin-23 (IL-23)/interleukin-17 (IL-17) axis plays a critical role in psoriasis. Here, we analyzed the effect of vanillin on imiquimod (IMQ)-induced psoriatic skin inflammation in mice. Mice were treated topically with IMQ on the back skin and orally with various amounts of vanillin for 7 consecutive days. Vanillin significantly improved IMQ-induced histopathological changes of skin in a dose-dependent manner. The thickness and number of cell layers of epidermis were reduced by 29 ± 14.4 and 27.8 ± 11%, respectively, in mice given 100 mg/kg of vanillin. A microarray showed that a total of 9042 IMQ-upregulated genes were downregulated by vanillin, and the biological pathways involved in the immune system and metabolism were significantly altered by vanillin. The upregulated expressions of IL-23, IL-17A, and IL-17F genes were suppressed by vanillin, with fold changes of -3.07 ± 0.08, -2.06 ± 0.21, and -1.62 ± 0.21, respectively. Moreover, vanillin significantly decreased both the amounts of IL-17A and IL-23 and the infiltration of immune cells in the skin tissues of IMQ-treated mice. In conclusion, our findings suggested that vanillin was an effective bioactive compound against psoriatic skin inflammation. Moreover, the downregulation of IL-23 and IL-17 expression suggested that vanillin was a novel regulator of the IL-23/IL-17 axis.

A tan in a test tube - in vitro models for investigating ultraviolet radiation-induced damage in skin.

Science.gov (United States)

Fernandez, Tara L; Dawson, Rebecca A; Van Lonkhuyzen, Derek R; Kimlin, Michael G; Upton, Zee

2012-06-01

Presently, global rates of skin cancers induced by ultraviolet radiation (UVR) exposure are on the rise. In view of this, current knowledge gaps in the biology of photocarcinogenesis and skin cancer progression urgently need to be addressed. One factor that has limited skin cancer research has been the need for a reproducible and physiologically-relevant model able to represent the complexity of human skin. This review outlines the main currently-used in vitro models of UVR-induced skin damage. This includes the use of conventional two-dimensional cell culture techniques and the major animal models that have been employed in photobiology and photocarcinogenesis research. Additionally, the progression towards the use of cultured skin explants and tissue-engineered skin constructs, and their utility as models of native skin's responses to UVR are described. The inherent advantages and disadvantages of these in vitro systems are also discussed. © 2012 John Wiley & Sons A/S.

Rapid allergen-induced interleukin-17 and interferon-γ secretion by skin-resident memory CD8(+) T cells

DEFF Research Database (Denmark)

Schmidt, Jonas D; Ahlström, Malin G; Johansen, Jeanne D

2017-01-01

, the mechanisms whereby TRM cells induce rapid recall responses need further investigation. OBJECTIVES: To study whether contact allergens induce local and/or global memory, and to determine the mechanisms involved in memory responses in the skin. METHODS: To address these questions, we analysed responses......BACKGROUND: Skin-resident memory T (TRM ) cells are associated with immunological memory in the skin. Whether immunological memory responses to allergens in the skin are solely localized to previously allergen-exposed sites or are present globally in the skin is not clear. Furthermore......, long-lasting local memory and a weaker, temporary global immunological memory response to the allergen that is mediated by IL-17A-producing and IFN-γ-producing CD8(+) TRM cells....

Histological and Ultrastructural Effects of Ultrasound-induced Cavitation on Human Skin Adipose Tissue.

Science.gov (United States)

Bani, Daniele; Quattrini Li, Alessandro; Freschi, Giancarlo; Russo, Giulia Lo

2013-09-01

In aesthetic medicine, the most promising techniques for noninvasive body sculpturing purposes are based on ultrasound-induced fat cavitation. Liporeductive ultrasound devices afford clinically relevant subcutaneous fat pad reduction without significant adverse reactions. This study aims at evaluating the histological and ultrastructural changes induced by ultrasound cavitation on the different cell components of human skin. Control and ultrasound-treated ex vivo abdominal full-thickness skin samples and skin biopsies from patients pretreated with or without ultrasound cavitation were studied histologically, morphometrically, and ultrastructurally to evaluate possible changes in adipocyte size and morphology. Adipocyte apoptosis and triglyceride release were also assayed. Clinical evaluation of the effects of 4 weekly ultrasound vs sham treatments was performed by plicometry. Compared with the sham-treated control samples, ultrasound cavitation induced a statistically significant reduction in the size of the adipocytes (P ultrasound treatment caused a significant reduction of abdominal fat. This study further strengthens the current notion that noninvasive transcutaneous ultrasound cavitation is a promising and safe technology for localized reduction of fat and provides experimental evidence for its specific mechanism of action on the adipocytes.

Radiation-Induced Skin Injuries to Patients: What the Interventional Radiologist Needs to Know.

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Jaschke, Werner; Schmuth, Matthias; Trianni, Annalisa; Bartal, Gabriel

2017-08-01

For a long time, radiation-induced skin injuries were only encountered in patients undergoing radiation therapy. In diagnostic radiology, radiation exposures of patients causing skin injuries were extremely rare. The introduction of fast multislice CT scanners and fluoroscopically guided interventions (FGI) changed the situation. Both methods carry the risk of excessive high doses to the skin of patients resulting in skin injuries. In the early nineties, several reports of epilation and skin injuries following CT brain perfusion studies were published. During the same time, several papers reported skin injuries following FGI, especially after percutaneous coronary interventions and neuroembolisations. Thus, CT and FGI are of major concern regarding radiation safety since both methods can apply doses to patients exceeding 5 Gy (National Council on Radiation Protection and Measurements threshold for substantial radiation dose level). This paper reviews the problem of skin injuries observed after FGI. Also, some practical advices are given how to effectively avoid skin injuries. In addition, guidelines are discussed how to deal with patients who were exposed to a potentially dangerous radiation skin dose during medically justified interventional procedures.

Free Radicals and Extrinsic Skin Aging

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Borut Poljšak

2012-01-01

Full Text Available Human skin is constantly directly exposed to the air, solar radiation, environmental pollutants, or other mechanical and chemical insults, which are capable of inducing the generation of free radicals as well as reactive oxygen species (ROS of our own metabolism. Extrinsic skin damage develops due to several factors: ionizing radiation, severe physical and psychological stress, alcohol intake, poor nutrition, overeating, environmental pollution, and exposure to UV radiation (UVR. It is estimated that among all these environmental factors, UVR contributes up to 80%. UV-induced generation of ROS in the skin develops oxidative stress, when their formation exceeds the antioxidant defence ability of the target cell. The primary mechanism by which UVR initiates molecular responses in human skin is via photochemical generation of ROS mainly formation of superoxide anion (O2−•, hydrogen peroxide (H2O2, hydroxyl radical (OH•, and singlet oxygen (1O2. The only protection of our skin is in its endogenous protection (melanin and enzymatic antioxidants and antioxidants we consume from the food (vitamin A, C, E, etc.. The most important strategy to reduce the risk of sun UVR damage is to avoid the sun exposure and the use of sunscreens. The next step is the use of exogenous antioxidants orally or by topical application and interventions in preventing oxidative stress and in enhanced DNA repair.

Oral administration of Bifidobacterium breve attenuates UV-induced barrier perturbation and oxidative stress in hairless mice skin.

Science.gov (United States)

Ishii, Yuki; Sugimoto, Saho; Izawa, Naoki; Sone, Toshiro; Chiba, Katsuyoshi; Miyazaki, Kouji

2014-07-01

Recent studies have shown that some probiotics affect not only the gut but also the skin. However, the effects of probiotics on ultraviolet (UV)-induced skin damage are poorly understood. In this study, we aim to examine whether oral administration of live Bifidobacterium breve strain Yakult (BBY), a typical probiotic, can attenuate skin barrier perturbation caused by UV and reactive oxygen species (ROS) in hairless mice. The mice were orally supplemented with a vehicle only or BBY once a day for nine successive days. Mouse dorsal skin was irradiated with UV from days 6 to 9. The day after the final irradiation, the transepidermal water loss (TEWL), stratum corneum hydration, and oxidation-related factors of the skin were evaluated. We elucidated that BBY prevented the UV-induced increase in TEWL and decrease in stratum corneum hydration. In addition, BBY significantly suppressed the UV-induced increase in hydrogen peroxide levels, oxidation of proteins and lipids, and xanthine oxidase activity in the skin. Conversely, antioxidant capacity did not change regardless of whether BBY was administered or not. In parameters we evaluated, there was a positive correlation between the increase in TEWL and the oxidation levels of proteins and lipids. Our results suggest that oral administration of BBY attenuates UV-induced barrier perturbation and oxidative stress of the skin, and this antioxidative effect is not attributed to enhancement of antioxidant capacity but to the prevention of ROS generation.

Effects of air pollution on the skin: A review.

Science.gov (United States)

Puri, Poonam; Nandar, Shashi Kumar; Kathuria, Sushruta; Ramesh, V

2017-01-01

The increase in air pollution over the years has had major effects on the human skin. Various air pollutants such as ultraviolet radiation, polycyclic aromatic hydrocarbons, volatile organic compounds, oxides, particulate matter, ozone and cigarette smoke affect the skin as it is the outermost barrier. Air pollutants damage the skin by inducing oxidative stress. Although human skin acts as a biological shield against pro-oxidative chemicals and physical air pollutants, prolonged or repetitive exposure to high levels of these pollutants may have profound negative effects on the skin. Exposure to ultraviolet radiation has been associated with extrinsic skin aging and skin cancers. Cigarette smoke contributes to premature aging and an increase in the incidence of psoriasis, acne and skin cancers. It is also implicated in allergic skin conditions such as atopic dermatitis and eczema. Polyaromatic hydrocarbons are associated with extrinsic skin aging, pigmentation, cancers and acneiform eruptions. Volatile organic compounds have been associated with atopic dermatitis. Given the increasing levels of air pollution and its detrimental effects on the skin, it is advisable to use strategies to decrease air pollution.

Epidermal Langerhans' cell induction of immunity against an ultraviolet-induced skin tumour

International Nuclear Information System (INIS)

Cavanagh, L.L.; Sluyter, R.; Henderson, K.G.; Barnetson, R.St.C.; Halliday, G.M.

1996-01-01

Lanerghans' cells (LC) have been shown experimentally to induce immune response against many antigens; however, their role in the initiation of anti-tumour immunity has received little attention. This study examined the ability of murine epidermal LC to induce immunity to an ultraviolet radiation (UV)-induced skin tumour. Freshly prepared epidermal cells (EC) were cultured for 2 or 20 hr with granulocyte-macrophage colony-stimulating factor (GM-CSF), pulsed with an extract of the UV-13-1 tumour, then used to immunize naive syngeneic mice. Delayed type hypersensitivity (DTH) was elicited 10 days after immunization by injection of UV-13-1 tumour cells into the ear pinna, and measured 24 hr later. EC cultured with GM-CSF for 2 hr induced anti-tumour DTH, as did EC cultured for 20 hr without GM-CSF. Conversely, EC cultured for 2 hr without GM-CSF, or EC cultured for 20 hr with GM-CSF were unable to induce a DTH. Induction of immunity required active presentation of tumour antigens by Ia + EC and was tumour specific. Thus Ia + epidermal cells are capable of inducing anti-tumour immunity to UV-induced skin tumours, but only when they contact antigen in particular states of maturation. (author)

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

Energy Technology Data Exchange (ETDEWEB)

Chang, Yoke-Chen; Wang, James D.; Hahn, Rita A.; Gordon, Marion K.; Joseph, Laurie B. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Heck, Diane E. [Department of Environmental Science, New York Medical College, Valhalla, NY (United States); Heindel, Ned D. [Department of Chemistry, Lehigh University, Bethlehem, PA (United States); Young, Sherri C. [Department of Chemistry, Muhlenberg College, Allentown, PA (United States); Sinko, Patrick J. [Department of Pharmaceutics, Rutgers University, Piscataway, NJ (United States); Casillas, Robert P. [MRIGlobal, Kansas City, MO (United States); Laskin, Jeffrey D. [Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ (United States); Laskin, Debra L. [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States); Gerecke, Donald R., E-mail: gerecke@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ (United States)

2014-10-15

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

Surface Lipids as Multifunctional Mediators of Skin Responses to Environmental Stimuli

Directory of Open Access Journals (Sweden)

Chiara De Luca

2010-01-01

Full Text Available Skin surface lipid (SSL film is a mixture of sebum and keratinocyte membrane lipids, protecting skin from environment. Its composition is unique for the high percentage of long chain fatty acids, and of the polyterpenoid squalene, absent in other human tissues, and in non-human Primates sebum. Here, the still incomplete body of information on SSL as mediators of external chemical, physical, and microbial signals and stressors is revised, focusing on the central event of the continuous oxidative modification induced by the metabolic activity of residential and pathological microbial flora, natural or iatrogenic UV irradiation, exposure to chemicals and cosmetics. Once alpha-tocopherol and ubiquinol-10 antioxidant defences of SSL are overcome, oxidation of squalene and cholesterol gives rise to reactive by-products penetrating deeper into skin layers, to mediate local defensive inflammatory, photo-protective, immune reactions or, at higher concentrations, inducing local but also systemic immune depression, ultimately implicating skin cancerogenesis. Qualitative modifications of SSL represent a pathogenetic sign of diagnostic value in dermatological disorders involving altered sebum production, like pytiriasis versicolor, acne, atopic or seborrheic dermatitis, as well as photo-aging. Achievements of nutriceutical interventions aimed at restoring normal SSL composition and homeostasis are discussed, as feasible therapeutic goals and major means of photo-protection.

Skin cancer induced by ultraviolet radiation and immunity

International Nuclear Information System (INIS)

Sado, Toshihiko

1977-01-01

It was clarified that an immunological mechanism, in which the resistance against ultraviolet radiation (UV)-induced neoplasm with strong antigenicity in the body disappeared, was introduced, when the mouse was exposed to UV for two to five weeks. It was also suggested that the immunological mechanism was an induction of T lymphocyte (inhibitive T cells) which had a function to specifically inhibit proliferation of lymphocyte clone which had anti-UV-induced neoplasm activity contained in lymphocyte mass of normal mouse. It can be thought that the action mechanism of this cells may inhibit a process of differentiation of T precursor cells of cell damage, which has anti-UV-induced neoplasm activity, into cell damage T cells. As a mechanism in which such inhibitive T cells are induced, the possibility that specific inhibitive T cells against antigens which are changed by UV would be induced after proteins, which receives some changes in consequence of skin injuries due to UV, are separated from cells as soluble antigens, is thought. Reports of experiments on these problems performed by many researchers were also described. (Tsunoda, M.)

Experimental skin carcinoma by UVB application

Directory of Open Access Journals (Sweden)

Andrada Iftode

2016-12-01

Full Text Available OBJECTIVES AND BACKGROUND The aim of this research study was to evaluate the harmful effects at skin level induced by concomitant and repeated exposure to three toxic agents: UVB radiation, DMBA and TPA. MATERIALS AND METHODS Experimental mice were divided in thw following groups (n=5 mice/group: group 1 – healthy mice, group 2 – mice exposed to UVB – radiation and topical administration of acetone and group 3 – mice exposed to UVB – radiation and topical application of DMBA and TPA solutions (phase I - double tumor initiation and phase II - tumor promotion. RESULTS Application of these compounds led to the development of skin papilloma and to significant changes in skin parameters. CONCLUSIONS The barrier function of the skin was degraded in UVB exposed mice. DMBA and TPA depended on carcinogens schedule and corelated with skin carcinoma. Graphical abstract: Schematic protocol of experimental skin carcinoma REFERENCES 1. Lee Ja, Ko Jh, Jung Bg, Kim Th, Hong Ji, Park Ys, Lee Bj. Fermented Prunus mume with Probiotics Inhibits 7,12- Dimethylbenz[a]anthracene and 12-OTetradecanoyl phorbol-13-acetate Induced Skin Carcinogenesis through Alleviation of Oxidative Stress. Asian Pac J Cancer Prev. 2013;14:2973-2978. 2. Firooz A, Sadr B, Babakoohi S, Sarraf-Yazdy M, Fanian F, Kazerouni-Timsar A, NassiriKashani M, Naghizadeh MM, Dowlati Y. Variation of Biophysical Parameters of the Skin with Age, Gender, and Body Region. Scientific World Journal. 2012; doi.org/10.1100/2012/386936 3. Gheorgheosu (Coricovac D, Borcan F, Balasz NI, Soica C, Simu G, Kemeny L, Dehelean CA. Evaluation of skin parameters in C57BL/6J mice exposed to chemical and environmental factors using non-invasive methods. J Agroalim Proc Technol. 2014;20:14-20.

Ultraviolet B (UVB) induced DNA damage affects alternative splicing in skin cells

International Nuclear Information System (INIS)

Munoz, M.J.; Nieto Moreno, N.; Kornblihtt, A.R.

2010-01-01

The ultraviolet (UV) radiation from the Sun that reaches the Earth's surface is a combination of low (UVA, 320-400 nm) and high (UVB, 290-320 nm) energy light. UVB light causes two types of mutagenic DNA lesions: thymine dimers and (6-4) photo-products. UVB mutagenesis is a critical step in the generation of different forms of skin cancer, which develops almost exclusively in sun exposed areas. We have previously shown that RNA polymerase II (pol II) hyperphosphorylation induced by UVC (254 nm) irradiation of non-skin cells inhibits pol II elongation rates which in turn affects alternative splicing (AS) patterns, altering the synthesis of pro- and anti-apoptotic isoforms of key proteins like Bcl-x or Caspase 9 (C9). Since the UVC radiation is fully filtered by the ozone layer and AS regulation in skin pathologies has been poorly studied, we decided to extend our studies to human keratinocytes in culture treated with UVB (302 nm) light. We observed that pol II hyperphosphorylation is increased upon UVB irradiation, being this modification necessary for the observed change in AS of a model cassette exon. Moreover, UVB irradiation induces the proapoptotic mRNA isoforms of Bcl-x and C9 consistently with a key role of AS in skin response to DNA damage. (authors)

Description and comparative study of physico-chemical parameters of the teleost fish skin mucus.

Science.gov (United States)

Guardiola, Francisco A; Cuartero, María; Del Mar Collado-González, María; Arizcún, Marta; Díaz Baños, F Guillermo; Meseguer, José; Cuesta, Alberto; Esteban, María A

2015-01-01

The study of mucosal surfaces, and in particular the fish skin and its secreted mucus, has been of great interest recently among immunologists. Measurement of the viscosity and other physico-chemical parameters (protein concentration, pH, conductivity, redox potential, osmolality and density) of the skin mucus can help to understand its biological functions. We have used five marine species of teleost: gilthead seabream (Sparus aurata L.), European sea bass (Dicentrarchus labrax L.), shi drum (Umbrina cirrosa L.), common dentex (Dentex dentex L.) and dusky grouper (Epinephelus marginatus L.), all of them with commercial interest in the aquaculture of the Mediterranean area. Mucus showed a direct shear- and temperature-dependent viscosity, with a non-Newtonian behavior, which differed however between two groups: one with higher viscosity (D. labrax, U. cirrosa, D. dentex) and the other with lower viscosity (S. aurata, E. marginatus). In addition, there was a clear interrelation between density and osmolality, as well as between density and temperature. Taking into account that high values of viscosity should improve the barrier effect against pathogens but low values of viscosity are needed for good locomotion characteristics, our results may help elucidate the relationship between physico-chemical and biological parameters of skin mucus, and disease susceptibility.

DNA damage by carbonyl stress in human skin cells

International Nuclear Information System (INIS)

Roberts, Michael J.; Wondrak, Georg T.; Laurean, Daniel Cervantes; Jacobson, Myron K.; Jacobson, Elaine L.

2003-01-01

Reactive carbonyl species (RCS) are potent mediators of cellular carbonyl stress originating from endogenous chemical processes such as lipid peroxidation and glycation. Skin deterioration as observed in photoaging and diabetes has been linked to accumulative protein damage from glycation, but the effects of carbonyl stress on skin cell genomic integrity are ill defined. In this study, the genotoxic effects of acute carbonyl stress on HaCaT keratinocytes and CF3 fibroblasts were assessed. Administration of the α-dicarbonyl compounds glyoxal and methylglyoxal as physiologically relevant RCS inhibited skin cell proliferation, led to intra-cellular protein glycation as evidenced by the accumulation of N ε -(carboxymethyl)-L-lysine (CML) in histones, and caused extensive DNA strand cleavage as assessed by the comet assay. These effects were prevented by treatment with the carbonyl scavenger D-penicillamine. Both glyoxal and methylglyoxal damaged DNA in intact cells. Glyoxal caused DNA strand breaks while methylglyoxal produced extensive DNA-protein cross-linking as evidenced by pronounced nuclear condensation and total suppression of comet formation. Glycation by glyoxal and methylglyoxal resulted in histone cross-linking in vitro and induced oxygen-dependent cleavage of plasmid DNA, which was partly suppressed by the hydroxyl scavenger mannitol. We suggest that a chemical mechanism of cellular DNA damage by carbonyl stress occurs in which histone glycoxidation is followed by reactive oxygen induced DNA stand breaks. The genotoxic potential of RCS in cultured skin cells and its suppression by a carbonyl scavenger as described in this study have implications for skin damage and carcinogenesis and its prevention by agents selective for carbonyl stress

DNA damage by carbonyl stress in human skin cells

Energy Technology Data Exchange (ETDEWEB)

Roberts, Michael J.; Wondrak, Georg T.; Laurean, Daniel Cervantes; Jacobson, Myron K.; Jacobson, Elaine L

2003-01-28

Reactive carbonyl species (RCS) are potent mediators of cellular carbonyl stress originating from endogenous chemical processes such as lipid peroxidation and glycation. Skin deterioration as observed in photoaging and diabetes has been linked to accumulative protein damage from glycation, but the effects of carbonyl stress on skin cell genomic integrity are ill defined. In this study, the genotoxic effects of acute carbonyl stress on HaCaT keratinocytes and CF3 fibroblasts were assessed. Administration of the {alpha}-dicarbonyl compounds glyoxal and methylglyoxal as physiologically relevant RCS inhibited skin cell proliferation, led to intra-cellular protein glycation as evidenced by the accumulation of N{sup {epsilon}}-(carboxymethyl)-L-lysine (CML) in histones, and caused extensive DNA strand cleavage as assessed by the comet assay. These effects were prevented by treatment with the carbonyl scavenger D-penicillamine. Both glyoxal and methylglyoxal damaged DNA in intact cells. Glyoxal caused DNA strand breaks while methylglyoxal produced extensive DNA-protein cross-linking as evidenced by pronounced nuclear condensation and total suppression of comet formation. Glycation by glyoxal and methylglyoxal resulted in histone cross-linking in vitro and induced oxygen-dependent cleavage of plasmid DNA, which was partly suppressed by the hydroxyl scavenger mannitol. We suggest that a chemical mechanism of cellular DNA damage by carbonyl stress occurs in which histone glycoxidation is followed by reactive oxygen induced DNA stand breaks. The genotoxic potential of RCS in cultured skin cells and its suppression by a carbonyl scavenger as described in this study have implications for skin damage and carcinogenesis and its prevention by agents selective for carbonyl stress.

The local lymph node assay: current position in the regulatory classification of skin sensitizing chemicals.

Science.gov (United States)

Basketter, David A; Gerberick, G Frank; Kimber, Ian

2007-01-01

The local lymph node assay (LLNA) is being used increasingly in the identification of skin sensitizing chemicals for regulatory purposes. In the context of new chemicals legislation (REACH) in Europe, it is the preferred assay. The rationale for this is that the LLNA quantitative and objective approach to skin sensitization testing allied with the important animal welfare benefits that the method offers. However, as with certain guinea pig sensitization tests before it, this increasing use also brings experience with an increasingly wide range of industrial and other chemicals where the outcome of the assay does not always necessarily meet with the expectations of those conducting it. Sometimes, the result appears to be a false negative, but rather more commonly, the complaint is that the chemical represents a false positive. Against this background we have here reviewed a number of instances where false positive and false negative results have been described and have sought to reconcile science with expectation. Based on these analyses, it is our conclusion that false positives and false negatives do occur in the LLNA, as they do with any other skin sensitization assay (and indeed with all tests used for hazard identification), and that this occurs for a number of reasons. We further conclude, however, that false positive results in the LLNA, as with the guinea pig maximization test, arise most commonly via failure to distinguish what is scientifically correct from that which is unpalatable. The consequences of this confusion are discussed in the article, particularly in relation to the need to integrate both potency measurement and risk assessments into classification and labelling schemes that aim to manage potential risks to human health.

Vasotocin- and mesotocin-induced increases in short-circuit current across tree frog skin.

Science.gov (United States)

Takada, Makoto; Fujimaki-Aoba, Kayo; Hokari, Shigeru

2011-02-01

In adult amphibian skin, Na(+) crosses from outside to inside. This Na(+) transport can be measured as the amiloride-blockable short-circuit current (SCC) across the skin. We investigated the effects of arginine vasotocin (AVT) and mesotocin (MT), and those of antagonists of the vasopressin and oxytocin receptors, on the SCC across Hyla japonica skin. (1) Both AVT (100 pmol/L or more) and MT (1 nmol/L or more) increased the SCC. (2) The AVT- and MT-induced increases in SCC recovered with time (downregulation). (3) These AVT/MT-induced effects were blocked by application of OPC-31260 (vasopressin V(2)-receptor antagonist). (4) The OPC-31260 concentration needed to block the AVT-induced response was lower upon post-application (after application of agonist) than upon pre-application (before application of agonist), suggesting the number of receptors may have decreased after AVT application. (5) Upon repeated application of AVT (100 pmol/L), the induced SCC increase did not differ significantly between the 1st and 2nd applications. (6) The time to reach the half-maximum value of the AVT-induced or MT-induced increase in SCC was not significantly different between washout and post-application of OPC-31260, suggesting that post-application of OPC-31260 cleared AVT and MT from their receptors. The effects of AVT, MT, and their antagonists in H. japonica, which is adapted to a terrestrial habitat, are compared with our previously published data on Rana catesbeiana (=Lithobates catesbeianus), which is adapted to a semiaquatic habitat.

Royal jelly protects against ultraviolet B-induced photoaging in human skin fibroblasts via enhancing collagen production.

Science.gov (United States)

Park, Hye Min; Hwang, Eunson; Lee, Kwang Gill; Han, Sang-Mi; Cho, Yunhi; Kim, Sun Yeou

2011-09-01

Royal jelly (RJ) is a honeybee product containing proteins, carbohydrates, fats, free amino acids, vitamins, and minerals. As its principal unsaturated fatty acid, RJ contains 10-hydroxy-2-decenoic acid (10-HDA), which may have antitumor and antibacterial activity and a capacity to stimulate collagen production. RJ has attracted interest in various parts of the world for its pharmacological properties. However, the effects of RJ on ultraviolet (UV)-induced photoaging of the skin have not been reported. In this study we measured the 10-HDA content of RJ by high-performance liquid chromatography and tested the effects of RJ on UVB-induced skin photoaging in normal human dermal fibroblasts. The effects of RJ and 10-HDA on UVB-induced photoaging were tested by measuring procollagen type I, transforming growth factor (TGF)-β1, and matrix metalloproteinase (MMP)-1 after UVB irradiation. The RJ contained about 0.211% 10-HDA. The UVB-irradiated human skin fibroblasts treated with RJ and 10-HDA had increased procollagen type I and TGF-β1 productions, but the level of MMP-1 was not changed. Thus RJ may potentially protect the skin from UVB-induced photoaging by enhancing collagen production.

Black tattoos protect against UVR-induced skin cancer in mice.

Science.gov (United States)

Lerche, Catharina M; Sepehri, Mitra; Serup, Jørgen; Poulsen, Thomas; Wulf, Hans Christian

2015-09-01

Black tattoos may involve risk of cancer owing to polycyclic aromatic hydrocarbons including benzo(a)pyrene (BaP) in inks. Ultraviolet radiation (UVR) induces skin cancer. The combination of UVR and black tattoo may therefore potentially be very problematic, but has not been previously studied. Immunocompetent C3.Cg/TifBomTac mice (n = 99) were tattooed on the back with Starbrite Tribal Black(™) . This ink has a high content of the carcinogen BaP. Half of the mice were irradiated with three standard erythema doses UVR thrice weekly. Time to induction of first, second and third squamous cell carcinoma (SCC) was measured. Controls were 'tattooed' without ink. All irradiated mice developed SCCs while no malignant tumours were found in the nonirradiated group. In the tattooed and irradiated group, the development of the first, second and third SCC was significantly delayed in comparison with the irradiated controls without black tattoos (212, 232, 247 days vs. 163, 183, 191 days, P tattoos, remarkably, the development of UVR-induced skin cancer was delayed by the tattoos. Skin reflectance measurement indicated that the protective effect of black pigment in the dermis might be attributed to UVR absorption by black pigment below the epidermis and thereby reduction of backscattered radiation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Absorption of radionuclide through wounded skin

International Nuclear Information System (INIS)

Kusama, Tomoko; Ogaki, Kazushi; Yoshizawa, Yasuo

1982-01-01

The translocation and absorption of 58 Co(CoCl 2 ) through a wound was investigated experimentally with mice. Physical and chemical skin damages became the objects of the investigation. Abrasion, puncture and incision were made for types of the physical damage. The chemical damage included both acid and alkaline burns. The absorptions of the radionuclide through the contaminated wounds were measured with both a 2 inches NaI(Tl) scintillation detector and an auto well gamma counter at 15,30 and 60 min after the contamination. The radionuclide was hardly absorbed through an undamaged skin. After 30 min, 20 to 40% of the radionuclide applied on the physically damaged skin was absorbed, but was not absorbed through the chemically damaged skin. The absorption rate through the physically damaged skin reached a maximum at 15 to 60 min after the contamination. The velocity of the absorption through the physically damaged skin was 100 times as much as the chemically damaged skin. The absorption rates through the physically and the chemically damaged skins were expressed by the following formulas: A=a(1-e sup(-bt)) and A=a(e sup(bt)-1), where a and b is constant, respectively. (author)

Visible Light Induces Melanogenesis in Human Skin through a Photoadaptive Response

Science.gov (United States)

Randhawa, Manpreet; Seo, InSeok; Liebel, Frank; Southall, Michael D.; Kollias, Nikiforos; Ruvolo, Eduardo

2015-01-01

Visible light (400–700 nm) lies outside of the spectral range of what photobiologists define as deleterious radiation and as a result few studies have studied the effects of visible light range of wavelengths on skin. This oversight is important considering that during outdoors activities skin is exposed to the full solar spectrum, including visible light, and to multiple exposures at different times and doses. Although the contribution of the UV component of sunlight to skin damage has been established, few studies have examined the effects of non-UV solar radiation on skin physiology in terms of inflammation, and limited information is available regarding the role of visible light on pigmentation. The purpose of this study was to determine the effect of visible light on the pro-pigmentation pathways and melanin formation in skin. Exposure to visible light in ex-vivo and clinical studies demonstrated an induction of pigmentation in skin by visible light. Results showed that a single exposure to visible light induced very little pigmentation whereas multiple exposures with visible light resulted in darker and sustained pigmentation. These findings have potential implications on the management of photo-aggravated pigmentary disorders, the proper use of sunscreens, and the treatment of depigmented lesions. PMID:26121474

Visible Light Induces Melanogenesis in Human Skin through a Photoadaptive Response.

Science.gov (United States)

Randhawa, Manpreet; Seo, InSeok; Liebel, Frank; Southall, Michael D; Kollias, Nikiforos; Ruvolo, Eduardo

2015-01-01

Visible light (400-700 nm) lies outside of the spectral range of what photobiologists define as deleterious radiation and as a result few studies have studied the effects of visible light range of wavelengths on skin. This oversight is important considering that during outdoors activities skin is exposed to the full solar spectrum, including visible light, and to multiple exposures at different times and doses. Although the contribution of the UV component of sunlight to skin damage has been established, few studies have examined the effects of non-UV solar radiation on skin physiology in terms of inflammation, and limited information is available regarding the role of visible light on pigmentation. The purpose of this study was to determine the effect of visible light on the pro-pigmentation pathways and melanin formation in skin. Exposure to visible light in ex-vivo and clinical studies demonstrated an induction of pigmentation in skin by visible light. Results showed that a single exposure to visible light induced very little pigmentation whereas multiple exposures with visible light resulted in darker and sustained pigmentation. These findings have potential implications on the management of photo-aggravated pigmentary disorders, the proper use of sunscreens, and the treatment of depigmented lesions.

Visible Light Induces Melanogenesis in Human Skin through a Photoadaptive Response.

Directory of Open Access Journals (Sweden)

Manpreet Randhawa

Full Text Available Visible light (400-700 nm lies outside of the spectral range of what photobiologists define as deleterious radiation and as a result few studies have studied the effects of visible light range of wavelengths on skin. This oversight is important considering that during outdoors activities skin is exposed to the full solar spectrum, including visible light, and to multiple exposures at different times and doses. Although the contribution of the UV component of sunlight to skin damage has been established, few studies have examined the effects of non-UV solar radiation on skin physiology in terms of inflammation, and limited information is available regarding the role of visible light on pigmentation. The purpose of this study was to determine the effect of visible light on the pro-pigmentation pathways and melanin formation in skin. Exposure to visible light in ex-vivo and clinical studies demonstrated an induction of pigmentation in skin by visible light. Results showed that a single exposure to visible light induced very little pigmentation whereas multiple exposures with visible light resulted in darker and sustained pigmentation. These findings have potential implications on the management of photo-aggravated pigmentary disorders, the proper use of sunscreens, and the treatment of depigmented lesions.

Chemical and engineering approaches to enable organic field-effect transistors for electronic skin applications.

Science.gov (United States)

Sokolov, Anatoliy N; Tee, Benjamin C-K; Bettinger, Christopher J; Tok, Jeffrey B-H; Bao, Zhenan

2012-03-20

Skin is the body's largest organ and is responsible for the transduction of a vast amount of information. This conformable material simultaneously collects signals from external stimuli that translate into information such as pressure, pain, and temperature. The development of an electronic material, inspired by the complexity of this organ is a tremendous, unrealized engineering challenge. However, the advent of carbon-based electronics may offer a potential solution to this long-standing problem. In this Account, we describe the use of an organic field-effect transistor (OFET) architecture to transduce mechanical and chemical stimuli into electrical signals. In developing this mimic of human skin, we thought of the sensory elements of the OFET as analogous to the various layers and constituents of skin. In this fashion, each layer of the OFET can be optimized to carry out a specific recognition function. The separation of multimodal sensing among the components of the OFET may be considered a "divide and conquer" approach, where the electronic skin (e-skin) can take advantage of the optimized chemistry and materials properties of each layer. This design of a novel microstructured gate dielectric has led to unprecedented sensitivity for tactile pressure events. Typically, pressure-sensitive components within electronic configurations have suffered from a lack of sensitivity or long mechanical relaxation times often associated with elastomeric materials. Within our method, these components are directly compatible with OFETs and have achieved the highest reported sensitivity to date. Moreover, the tactile sensors operate on a time scale comparable with human skin, making them ideal candidates for integration as synthetic skin devices. The methodology is compatible with large-scale fabrication and employs simple, commercially available elastomers. The design of materials within the semiconductor layer has led to the incorporation of selectivity and sensitivity within

Fishing gear-induced skin ulcerations in Baltic cod, Gadus morhua L

DEFF Research Database (Denmark)

Mellergaard, Stig; Bagge, O.

1998-01-01

In 1982 a high prevalence of skin ulcerations was observed in Baltic cod in the vicinity of the Danish island of Bornholm. In March the prevalence varied from G to 13%, and in May it had increased to between 26 and 48%. The ulcerations had a sequential development. The initial stage appeared...... from the nets, combined with bilateral occurrence of the ulcers, strongly indicates that the skin ulcers were induced by the fishing gear. Features of the pathology could be linked to the temporary retention of cod in trawl meshes....

A dicyanotriterpenoid induces cytoprotective enzymes and reduces multiplicity of skin tumors in UV-irradiated mice

International Nuclear Information System (INIS)

Dinkova-Kostova, Albena T.; Jenkins, Stephanie N.; Wehage, Scott L.; Huso, David L.; Benedict, Andrea L.; Stephenson, Katherine K.; Fahey, Jed W.; Liu Hua; Liby, Karen T.; Honda, Tadashi; Gribble, Gordon W.; Sporn, Michael B.; Talalay, Paul

2008-01-01

Inducible phase 2 enzymes constitute a primary line of cellular defense. The oleanane dicyanotriterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile (TP-225) is a very potent inducer of these systems. Topical application of TP-225 to SKH-1 hairless mice increases the levels of NAD(P)H-quinone acceptor oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) and protects against UV radiation-induced dermal thickening. Daily topical treatments of 10 nmol of TP-225 to the backs of mice that were previously subjected to low-level chronic UVB radiation (30 mJ/cm 2 /session, twice a week for 17 weeks), led to 50% reduction in multiplicity of skin tumors. In addition, the total tumor burden of squamous cell carcinomas was reduced by 5.5-fold. The identification of new agents for protection against UV radiation-induced skin cancer and understanding of their mechanism(s) of action is especially important in view of the fact that human skin cancers represent a significant source of increasing morbidity and mortality

Thread Embedding Acupuncture Inhibits Ultraviolet B Irradiation-Induced Skin Photoaging in Hairless Mice

Directory of Open Access Journals (Sweden)

Yoon-Jung Kim

2015-01-01

Full Text Available Thread embedding acupuncture (TEA is an acupuncture treatment applied to many diseases in Korean medical clinics because of its therapeutic effects by continuous stimulation to tissues. It has recently been used to enhance facial skin appearance and antiaging, but data from evidence-based medicine are limited. To investigate whether TEA therapy can inhibit skin photoaging by ultraviolet B (UVB irradiation, we performed analyses for histology, histopathology, in situ zymography and western blot analysis in HR-1 hairless mice. TEA treatment resulted in decreased wrinkle formation and skin thickness (Epidermis; P=0.001 versus UV in UVB irradiated mice and also inhibited degradation of collagen fibers (P=0.010 versus normal by inhibiting proteolytic activity of gelatinase matrix-metalloproteinase-9 (MMP-9. Western blot data showed that activation of c-Jun N-terminal kinase (JNK induced by UVB (P=0.002 versus normal group was significantly inhibited by TEA treatment (P=0.005 versus UV with subsequent alleviation of MMP-9 activation (P=0.048 versus UV. These results suggest that TEA treatment can have anti-photoaging effects on UVB-induced skin damage by maintenance of collagen density through regulation of expression of MMP-9 and related JNK signaling. Therefore, TEA therapy may have potential roles as an alternative treatment for protection against skin damage from aging.

Skin exposure to isocyanates: reasons for concern.

Science.gov (United States)

Bello, Dhimiter; Herrick, Christina A; Smith, Thomas J; Woskie, Susan R; Streicher, Robert P; Cullen, Mark R; Liu, Youcheng; Redlich, Carrie A

2007-03-01

Isocyanates (di- and poly-), important chemicals used worldwide to produce polyurethane products, are a leading cause of occupational asthma. Respiratory exposures have been reduced through improved hygiene controls and the use of less-volatile isocyanates. Yet isocyanate asthma continues to occur, not uncommonly in settings with minimal inhalation exposure but opportunity for skin exposure. In this review we evaluate the potential role of skin exposure in the development of isocyanate asthma. We reviewed the published animal and human literature on isocyanate skin-exposure methods, workplace skin exposure, skin absorption, and the role of skin exposure in isocyanate sensitization and asthma. We selected relevant articles from computerized searches on Medline, U.S. Environmental Protection Agency, Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, and Google databases using the keywords "isocyanate," "asthma," "skin," "sensitization," and other synonymous terms, and our own extensive collection of isocyanate publications. Isocyanate production and use continues to increase as the polyurethane industry expands. There is substantial opportunity for isocyanate skin exposure in many work settings, but such exposure is challenging to quantify and continues to be underappreciated. Isocyanate skin exposure can occur at work, even with the use of personal protective equipment, and may also occur with consumer use of certain isocyanate products. In animals, isocyanate skin exposure is an efficient route to induce sensitization, with subsequent inhalation challenge resulting in asthma-like responses. Several lines of evidence support a similar role for human isocyanate skin exposure, namely, that such exposure occurs and can contribute to the development of isocyanate asthma in certain settings, presumably by inducing systemic sensitization. Integrated animal and human research is needed to better understand the role of skin

Resolution of PMA-Induced Skin Inflammation Involves Interaction of IFN-γ and ALOX15

Directory of Open Access Journals (Sweden)

Guojun Zhang

2013-01-01

Full Text Available Background. Acute inflammation and its timely resolution play important roles in the body’s responses to the environmental stimulation. Although IFN-γ is well known for the induction of inflammation, its role in the inflammation resolution is still poorly understood. Methodology and Principal Findings. In this study, we investigated the function of interferon gamma (IFN-γ during the resolution of PMA-induced skin inflammation in vivo. The results revealed that the expression levels of IL-6, TNF-α, and monocyte chemoattractant protein 1 (MCP-1 in skin decreased during the resolution stage of PMA-induced inflammation, while IFN-γ is still maintained at a relatively high level. Neutralization of endogenous IFN-γ led to accelerated reduction of epidermal thickness and decreased epithelial cell proliferation. Similarly, decreased infiltration of inflammatory cells (Gr1+ or CD11b+ cells and a significant reduction of proinflammatory cytokines were also observed upon the blockade of IFN-γ. Furthermore, neutralization of IFN-γ boosted ALOX15 expression of the skin during inflammation resolution. In accordance, application of lipoxin A4 (LXA4, a product of ALOX15 obtained a proresolution effect similar to neutralization of IFN-γ. These results demonstrated that through upregulating ALOX15-LXA4 pathway, blockage of IFN-γ can promote the resolution of PMA-induced skin inflammation.

Cryotherapy-Induced Persistent Vasoconstriction After Cutaneous Cooling: Hysteresis Between Skin Temperature and Blood Perfusion

Science.gov (United States)

Khoshnevis, Sepideh; Craik, Natalie K.; Matthew Brothers, R.; Diller, Kenneth R.

2016-01-01

The goal of this study was to investigate the persistence of cold-induced vasoconstriction following cessation of active skin-surface cooling. This study demonstrates a hysteresis effect that develops between skin temperature and blood perfusion during the cooling and subsequent rewarming period. An Arctic Ice cryotherapy unit (CTU) was applied to the knee region of six healthy subjects for 60 min of active cooling followed by 120 min of passive rewarming. Multiple laser Doppler flowmetry perfusion probes were used to measure skin blood flow (expressed as cutaneous vascular conductance (CVC)). Skin surface cooling produced a significant reduction in CVC (P cryotherapy. PMID:26632263

Laser-induced capillary leakage for blood biomarker detection and vaccine delivery via the skin.

Science.gov (United States)

Wu, Jeffrey H; Li, Bo; Wu, Mei X

2016-07-01

Circulation system is the center for coordination and communication of all organs in our body. Examination of any change in its analytes or delivery of therapeutic drugs into the system consists of important medical practice in today's medicine. Two recent studies prove that brief illumination of skin with a low powered laser, at wavelengths preferentially absorbed by hemoglobin, increases the amount of circulating biomarkers in the epidermis and upper dermis by more than 1,000-fold. When probe-coated microneedle arrays are applied into laser-treated skin, plasma blood biomarkers can be reliably, accurately, and sufficiently quantified in 15∼30 min assays, with a maximal detection in one hr in a manner independent of penetration depth or a molecular mass of the biomarker. Moreover, the laser treatment permits a high efficient delivery of radiation-attenuated malarial sporozoites (RAS) into the circulation, leading to robust immunity against malaria infections, whereas similar immunization at sham-treated skin elicits poor immune responses. Thus this technology can potentially instruct designs of small, portable devices for onsite, in mobile clinics, or at home for point-of-care diagnosis and drug/vaccine delivery via the skin. Laser-induced capillary leakage (a) to induce extravasation of circualing molecules only (b) or facilitate entry of attenuated malaria sporozoites into the capillary (c). Skin illumination with a laser preferably absorbed by hemoglobin causes dilation of the capillary beneath the skin. The extravasated molecules can be sufficiently measured in the skin or guide sporozoites to enter the vessel. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Methoxyflavonoid Isosakuranetin Suppresses UV-B-Induced Matrix Metalloproteinase-1 Expression and Collagen Degradation Relevant for Skin Photoaging

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Hana Jung

2016-09-01

Full Text Available Solar ultraviolet (UV radiation is a main extrinsic factor for skin aging. Chronic exposure of the skin to UV radiation causes the induction of matrix metalloproteinases (MMPs, such as MMP-1, and consequently results in alterations of the extracellular matrix (ECM and skin photoaging. Flavonoids are considered as potent anti-photoaging agents due to their UV-absorbing and antioxidant properties and inhibitory activity against UV-mediated MMP induction. To identify anti-photoaging agents, in the present study we examined the preventative effect of methoxyflavonoids, such as sakuranetin, isosakuranetin, homoeriodictyol, genkwanin, chrysoeriol and syringetin, on UV-B-induced skin photo-damage. Of the examined methoxyflavonoids, pretreatment with isosakuranetin strongly suppressed the UV-B-mediated induction of MMP-1 in human keratinocytes in a concentration-dependent manner. Isosakuranetin inhibited UV-B-induced phosphorylation of mitogen-activated protein kinase (MAPK signaling components, ERK1/2, JNK1/2 and p38 proteins. This result suggests that the ERK1/2 kinase pathways likely contribute to the inhibitory effects of isosakuranetin on UV-induced MMP-1 production in human keratinocytes. Isosakuranetin also prevented UV-B-induced degradation of type-1 collagen in human dermal fibroblast cells. Taken together, our findings suggest that isosakuranetin has the potential for development as a protective agent for skin photoaging through the inhibition of UV-induced MMP-1 production and collagen degradation.

Polyhydroxylated fatty alcohols derived from avocado suppress inflammatory response and provide non-sunscreen protection against UV-induced damage in skin cells.

Science.gov (United States)

Rosenblat, Gennady; Meretski, Shai; Segal, Joseph; Tarshis, Mark; Schroeder, Avi; Zanin-Zhorov, Alexandra; Lion, Gilead; Ingber, Arieh; Hochberg, Malka

2011-05-01

Exposing skin to ultraviolet (UV) radiation contributes to photoaging and to the development of skin cancer by DNA lesions and triggering inflammatory and other harmful cellular cascades. The present study tested the ability of unique lipid molecules, polyhydroxylated fatty alcohols (PFA), extracted from avocado, to reduce UVB-induced damage and inflammation in skin. Introducing PFA to keratinocytes prior to their exposure to UVB exerted a protective effect, increasing cell viability, decreasing the secretion of IL-6 and PGE(2), and enhancing DNA repair. In human skin explants, treating with PFA reduced significantly UV-induced cellular damage. These results support the idea that PFA can play an important role as a photo-protective agent in UV-induced skin damage.

Cancer-promoting effect of capsaicin on DMBA/TPA-induced skin tumorigenesis by modulating inflammation, Erk and p38 in mice.

Science.gov (United States)

Liu, Zhaoguo; Zhu, Pingting; Tao, Yu; Shen, Cunsi; Wang, Siliang; Zhao, Lingang; Wu, Hongyan; Fan, Fangtian; Lin, Chao; Chen, Chen; Zhu, Zhijie; Wei, Zhonghong; Sun, Lihua; Liu, Yuping; Wang, Aiyun; Lu, Yin

2015-07-01

Epidemiologic and animal studies revealed that capsaicin (8-methyl-N-vanillyl-6-noneamide) can act as a carcinogen or cocarcinogen. However, the influence of consumption of capsaicin-containing foods or vegetables on skin cancer patients remains largely unknown. In the present study, we demonstrated that capsaicin has a cocarcinogenic effect on 9, 10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis. Our results showed that topical application of capsaicin on the dorsal skin of DMBA-initiated and TPA-promoted mice could significantly accelerate tumor formation and growth and induce more and larger skin tumors than the model group (DMBA + TPA). Moreover, capsaicin could promote TPA-induced skin hyperplasia and tumor proliferation. Mechanistic study found that inflammation-related factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were highly elevated by pretreatment with capsaicin, suggesting an inflammation-dependent mechanism. Furthermore, mice that were administered capsaicin exhibited significant up-regulation of phosphorylation of nuclear factor kappaB (NF-κB), Erk and p38 but had no effect on JNK. Thus, our results indicated that inflammation, Erk and P38 collectively played a crucial role in cancer-promoting effect of capsaicin on carcinogen-induced skin cancer in mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inventory of the chemicals and the exposure of the workers' skin to these at two leather factories in Indonesia

NARCIS (Netherlands)

Febriana, Sri Awalia; Jungbauer, Frank; Soebono, Hardyanto; Coenraads, Pieter-Jan

Tannery workers are exposed to hazardous chemicals. Tannery work is outsourced to newly industrialized countries (NICs) where attention into occupational health hazards is limited. In this study, we investigated the skin exposure to hazardous chemicals in tannery workers and determined the

Immune sensitization to methylene diphenyl diisocyanate (MDI resulting from skin exposure: albumin as a carrier protein connecting skin exposure to subsequent respiratory responses

Directory of Open Access Journals (Sweden)

Redlich Carrie A

2011-03-01

Full Text Available Abstract Background Methylene diphenyl diisocyanate (MDI, a reactive chemical used for commercial polyurethane production, is a well-recognized cause of occupational asthma. The major focus of disease prevention efforts to date has been respiratory tract exposure; however, skin exposure may also be an important route for inducing immune sensitization, which may promote subsequent airway inflammatory responses. We developed a murine model to investigate pathogenic mechanisms by which MDI skin exposure might promote subsequent immune responses, including respiratory tract inflammation. Methods Mice exposed via the skin to varying doses (0.1-10% w/v of MDI diluted in acetone/olive oil were subsequently evaluated for MDI immune sensitization. Serum levels of MDI-specific IgG and IgE were measured by enzyme-linked immunosorbant assay (ELISA, while respiratory tract inflammation, induced by intranasal delivery of MDI-mouse albumin conjugates, was evaluated based on bronchoalveolar lavage (BAL. Autologous serum IgG from "skin only" exposed mice was used to detect and guide the purification/identification of skin proteins antigenically modified by MDI exposure in vivo. Results Skin exposure to MDI resulted in specific antibody production and promoted subsequent respiratory tract inflammation in animals challenged intranasally with MDI-mouse albumin conjugates. The degree of (secondary respiratory tract inflammation and eosinophilia depended upon the (primary skin exposure dose, and was maximal in mice exposed to 1% MDI, but paradoxically limited in mice receiving 10-fold higher doses (e.g. 10% MDI. The major antigenically-modified protein at the local MDI skin exposure site was identified as albumin, and demonstrated biophysical changes consistent with MDI conjugation. Conclusions MDI skin exposure can induce MDI-specific immune sensitivity and promote subsequent respiratory tract inflammatory responses and thus, may play an important role in MDI asthma

CK1α ablation in keratinocytes induces p53-dependent, sunburn-protective skin hyperpigmentation.

Science.gov (United States)

Chang, Chung-Hsing; Kuo, Che-Jung; Ito, Takamichi; Su, Yu-Ya; Jiang, Si-Tse; Chiu, Min-Hsi; Lin, Yi-Hsiung; Nist, Andrea; Mernberger, Marco; Stiewe, Thorsten; Ito, Shosuke; Wakamatsu, Kazumasa; Hsueh, Yi-An; Shieh, Sheau-Yann; Snir-Alkalay, Irit; Ben-Neriah, Yinon

2017-09-19

Casein kinase 1α (CK1α), a component of the β-catenin destruction complex, is a critical regulator of Wnt signaling; its ablation induces both Wnt and p53 activation. To characterize the role of CK1α (encoded by Csnk1a1 ) in skin physiology, we crossed mice harboring floxed Csnk1a1 with mice expressing K14-Cre-ER T2 to generate mice in which tamoxifen induces the deletion of Csnk1a1 exclusively in keratinocytes [single-knockout (SKO) mice]. As expected, CK1α loss was accompanied by β-catenin and p53 stabilization, with the preferential induction of p53 target genes, but phenotypically most striking was hyperpigmentation of the skin, importantly without tumorigenesis, for at least 9 mo after Csnk1a1 ablation. The number of epidermal melanocytes and eumelanin levels were dramatically increased in SKO mice. To clarify the putative role of p53 in epidermal hyperpigmentation, we established K14-Cre-ER T2 CK1α/p53 double-knockout (DKO) mice and found that coablation failed to induce epidermal hyperpigmentation, demonstrating that it was p53-dependent. Transcriptome analysis of the epidermis revealed p53-dependent up-regulation of Kit ligand (KitL). SKO mice treated with ACK2 (a Kit-neutralizing antibody) or imatinib (a Kit inhibitor) abrogated the CK1α ablation-induced hyperpigmentation, demonstrating that it requires the KitL/Kit pathway. Pro-opiomelanocortin (POMC), a precursor of α-melanocyte-stimulating hormone (α-MSH), was not activated in the CK1α ablation-induced hyperpigmentation, which is in contrast to the mechanism of p53-dependent UV tanning. Nevertheless, acute sunburn effects were successfully prevented in the hyperpigmented skin of SKO mice. CK1α inhibition induces skin-protective eumelanin but no carcinogenic pheomelanin and may therefore constitute an effective strategy for safely increasing eumelanin via UV-independent pathways, protecting against acute sunburn.

Cutaneous Leishmaniasis Induces a Transmissible Dysbiotic Skin Microbiota that Promotes Skin Inflammation.

Science.gov (United States)

Gimblet, Ciara; Meisel, Jacquelyn S; Loesche, Michael A; Cole, Stephen D; Horwinski, Joseph; Novais, Fernanda O; Misic, Ana M; Bradley, Charles W; Beiting, Daniel P; Rankin, Shelley C; Carvalho, Lucas P; Carvalho, Edgar M; Scott, Phillip; Grice, Elizabeth A

2017-07-12

Skin microbiota can impact allergic and autoimmune responses, wound healing, and anti-microbial defense. We investigated the role of skin microbiota in cutaneous leishmaniasis and found that human patients infected with Leishmania braziliensis develop dysbiotic skin microbiota, characterized by increases in the abundance of Staphylococcus and/or Streptococcus. Mice infected with L. major exhibit similar changes depending upon disease severity. Importantly, this dysbiosis is not limited to the lesion site, but is transmissible to normal skin distant from the infection site and to skin from co-housed naive mice. This observation allowed us to test whether a pre-existing dysbiotic skin microbiota influences disease, and we found that challenging dysbiotic naive mice with L. major or testing for contact hypersensitivity results in exacerbated skin inflammatory responses. These findings demonstrate that a dysbiotic skin microbiota is not only a consequence of tissue stress, but also enhances inflammation, which has implications for many inflammatory cutaneous diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Use of silicon for skin and hair care: an approach of chemical forms available and efficacy.

Science.gov (United States)

Araújo, Lidiane Advincula de; Addor, Flavia; Campos, Patrícia Maria Berardo Gonçalves Maia

2016-01-01

Silicon is the second most abundant element on Earth, and the third most abundant trace element in human body. It is present in water, plant and animal sources. On the skin, it is suggested that silicon is important for optimal collagen synthesis and activation of hydroxylating enzymes, improving skin strength and elasticity. Regarding hair benefits, it was suggested that a higher silicon content in the hair results in a lower rate of hair loss and increased brightness. For these beneficial effects, there is growing interest in scientific studies evaluating the efficacy and safety of using dietary supplements containing silicon. Its use aims at increasing blood levels of this element and improving the skin and its annexes appearance. There are different forms of silicon supplements available and the most important consideration to be made in order to select the best option is related to safety and bioavailability. Silicon supplements are widely used, though there is wide variation in silicon bioavailability, ranging from values below 1% up to values close to 50%, depending on the chemical form. Therefore, the aim of this study was to evaluate the scientific literature related to the different chemical forms of silicon supplements available and the limitations and recent progress in this field. According to reported studies, among the different chemical forms available, the orthosilicic acid (OSA) presents the higher bioavailability, whereas the others forms have absorption inversely proportional to the degree of polymerization. However, clinical studies evaluating safety and efficacy are still lacking.

Ability of radiation therapists to assess radiation-induced skin toxicity

International Nuclear Information System (INIS)

Acharya, Urvi; Cox, Jennifer; Rinks, Marianne; Gaur, Pankaj; Back, Michael

2013-01-01

Radiation therapy has seen enhancement of the radiation therapist (RT) role, with RTs and nurses performing duties that were traditionally in the radiation oncologist's (RO) domain. This study aimed to assess whether RTs can consistently grade radiation-induced skin toxicity and their concordance with the gradings given by ROs. Digital photographs of skin reactions were taken at weeks 1, 3 and 6 of radiotherapy on nine patients with breast cancer. The randomly ordered photographs were reviewed once by eight ROs and four RO registrars and on two occasions separated by 6 weeks by 17 RTs. All graded the skin toxicities using the revised Radiation Therapy Oncology Group system. No significant difference was seen between the median scores of the RTs at the first scoring session and the RO/Registrar group. The RTs at both measurement times showed greater inter-rater reliability than the RO/Registrars (W=0.6866, time 1 and 0.6981 time 2, vs. 0.6517), with the experienced RTs the most consistent (W=0.7078). The RTs also showed high intra-rater reliability (rho=0.8461, P<0.0010). These results from RTs with no specific preparation indicate that experienced RTs could assess breast cancer skin toxicity as part of their role.

Inspection of arterial-induced skin vibration by Moire fringe with two-dimensional continuous wavelet transform

Science.gov (United States)

Wang, Chun-Hsiung; Chiu, Shih-Yung; Hsu, Yu-Hsiang; Lee, Shu-Sheng; Lee, Chih-Kung

2017-06-01

A non-contact arterial-induced skin vibration inspection system is implemented. This optical metrology system is constructed with shadow Moiré configuration and the fringe analysis algorithm. Developed with the Region of Interested (ROI) capturing technique and the Two-dimensional Wavelet Transform (2D-CWT) method, this algorithm is able to retrieve the height-correlated phase information from the shadow Moiré fringe patterns. Using a commercial video camera or a CMOS image sensor, this system could monitor the skin-vibration induced by the cyclic deformation of inner layered artery. The cross-sectional variation and the rhythm of heart cycle could be continuously measured for health monitoring purposes. The average vibration amplitude of the artery at the wrist ranges between 20 μm and 50 μm, which is quite subtle comparing with the skin surface structure. Having the non-stationary motion of human body, the traditional phase shifting (PS) technique can be very unstable due to the requirement of several frames of images, especially for case that artery is continuously pumping. To bypass this fundamental issue, the shadow Moiré technique is introduced to enhance the surface deformation characteristic. And the phase information is retrieved by the means of spectrum filtering instead of PS technique, which the phase is calculated from intensity maps of multiple images. The instantaneous surface can therefore be reconstructed individually from each frame, enabling the subtle arterial-induced skin vibration measurement. The comparative results of phase reconstruction between different fringe analysis algorithms will be demonstrated numerically and experimentally. And the electrocardiography (ECG) results will used as the reference for the validity of health monitoring potential of the non-contact arterial-induced skin vibration inspection system.

Solar ultraviolet radiation induces biological alterations in human skin in vitro: Relevance of a well-balanced UVA/UVB protection

Directory of Open Access Journals (Sweden)

Françoise Bernerd

2012-01-01

Full Text Available Cutaneous damages such as sunburn, pigmentation, and photoaging are known to be induced by acute as well as repetitive sun exposure. Not only for basic research, but also for the design of the most efficient photoprotection, it is crucial to understand and identify the early biological events occurring after ultraviolet (UV exposure. Reconstructed human skin models provide excellent and reliable in vitro tools to study the UV-induced alterations of the different skin cell types, keratinocytes, fibroblasts, and melanocytes in a dose- and time-dependent manner. Using different in vitro human skin models, the effects of UV light (UVB and UVA were investigated. UVB-induced damages are essentially epidermal, with the typical sunburn cells and DNA lesions, whereas UVA radiation-induced damages are mostly located within the dermal compartment. Pigmentation can also be obtained after solar simulated radiation exposure of pigmented reconstructed skin model. Those models are also highly adequate to assess the potential of sunscreens to protect the skin from UV-associated damage, sunburn reaction, photoaging, and pigmentation. The results showed that an effective photoprotection is provided by broad-spectrum sunscreens with a potent absorption in both UVB and UVA ranges.

Solar ultraviolet radiation induces biological alterations in human skin in vitro: relevance of a well-balanced UVA/UVB protection.

Science.gov (United States)

Bernerd, Francoise; Marionnet, Claire; Duval, Christine

2012-06-01

Cutaneous damages such as sunburn, pigmentation, and photoaging are known to be induced by acute as well as repetitive sun exposure. Not only for basic research, but also for the design of the most efficient photoprotection, it is crucial to understand and identify the early biological events occurring after ultraviolet (UV) exposure. Reconstructed human skin models provide excellent and reliable in vitro tools to study the UV-induced alterations of the different skin cell types, keratinocytes, fibroblasts, and melanocytes in a dose- and time-dependent manner. Using different in vitro human skin models, the effects of UV light (UVB and UVA) were investigated. UVB-induced damages are essentially epidermal, with the typical sunburn cells and DNA lesions, whereas UVA radiation-induced damages are mostly located within the dermal compartment. Pigmentation can also be obtained after solar simulated radiation exposure of pigmented reconstructed skin model. Those models are also highly adequate to assess the potential of sunscreens to protect the skin from UV-associated damage, sunburn reaction, photoaging, and pigmentation. The results showed that an effective photoprotection is provided by broad-spectrum sunscreens with a potent absorption in both UVB and UVA ranges.

Microemulsion Using Polyoxyethylene Sorbitan Trioleate and its Usage for Skin Delivery of Resveratrol to Protect Skin against UV-Induced Damage.

Science.gov (United States)

Yutani, Reiko; Teraoka, Reiko; Kitagawa, Shuji

2015-01-01

We examined the phase behavior of various polyoxyethylene sorbitan fatty acid ester (polysorbates)/ethanol/isopropyl myristate (IPM)/150 mM NaCl solution (NaClaq) systems in order to prepare a microemulsion containing a low ratio of ethanol, which is more suitable for in vivo application. Using polyoxyethylene sorbitan trioleate (Tween 85), which has a large lipophilic moiety, as a surfactant component, single-phase domain of the phase diagram was the largest of all the polysorbates examined, and in particular a large oil-rich single-phase domain was obtained. When the ratio of Tween 85 to ethanol was changed from 1 : 1 to 3 : 1, the oil-rich single-phase domain further expanded, which led to a reduced ethanol concentration in the preparation. Thus, we determined the composition of the microemulsion to be Tween 85 : ethanol : IPM : NaClaq=30 : 10 : 53 : 7, and used it for skin delivery of resveratrol. Microemulsion gel was also prepared by adding 6.5% Aerosil) 200 into the microemulsion for ease of topical application. When applied with each vehicle, delivery of resveratrol into guinea pig skin in vitro was significantly enhanced compared with that by IPM, and resveratrol incorporated into the skin by microemulsion gel decreased lipid peroxidation to 29.5% compared with that of the control. Pretreatment of guinea pig dorsal skin with the microemulsion gel containing resveratrol almost completely prevented UV-B-induced erythema formation in vivo. These findings demonstrate that the microemulsion using Tween 85 containing a minimal concentration of ethanol enhanced the skin delivery of resveratrol and the incorporated resveratrol exhibited a protective effect against UV-induced oxidative damage.

Skin changes in streptozotocin-induced diabetic rats.

Science.gov (United States)

Andrade, Thiago Antônio Moretti; Masson-Meyers, Daniela Santos; Caetano, Guilherme Ferreira; Terra, Vânia Aparecida; Ovidio, Paula Payão; Jordão-Júnior, Alceu Afonso; Frade, Marco Andrey Cipriani

2017-09-02

Diabetes can cause serious health complications, which can affect every organ of the body, including the skin. The molecular etiology has not yet been clarified for all diabetic skin conditions. Thus, this study aimed to investigate the changes of diabetes in skin compared to non-diabetic skin in rats. Fifteen days after establishing the diabetic status, skin samples from the dorsum-cervical region were harvested for subsequent analysis of alterations caused by diabetes. Our results demonstrate that diabetes stimulated higher inflammation and oxidative stress in skin, but antioxidant defense levels were lower compared to the non-diabetic group (p skin changes compared to non-diabetic skin in rats. Copyright © 2017 Elsevier Inc. All rights reserved.

Human skin volatiles: a review.

Science.gov (United States)

Dormont, Laurent; Bessière, Jean-Marie; Cohuet, Anna

2013-05-01

Odors emitted by human skin are of great interest to biologists in many fields; applications range from forensic studies to diagnostic tools, the design of perfumes and deodorants, and the ecology of blood-sucking insect vectors of human disease. Numerous studies have investigated the chemical composition of skin odors, and various sampling methods have been used for this purpose. The literature shows that the chemical profile of skin volatiles varies greatly among studies, and the use of different sampling procedures is probably responsible for some of these variations. To our knowledge, this is the first review focused on human skin volatile compounds. We detail the different sampling techniques, each with its own set of advantages and disadvantages, which have been used for the collection of skin odors from different parts of the human body. We present the main skin volatile compounds found in these studies, with particular emphasis on the most frequently studied body regions, axillae, hands, and feet. We propose future directions for promising experimental studies on odors from human skin, particularly in relation to the chemical ecology of blood-sucking insects.

Temporal and spatial features of the formation of DNA adducts in sulfur mustard-exposed skin

Energy Technology Data Exchange (ETDEWEB)

Batal, Mohamed [Laboratoire «Lésions des Acides Nucléiques», Université Joseph Fourier – Grenoble 1, CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble (France); Département de Toxicologie et Risques Chimiques, Unité de Brûlure Chimique, Institut de Recherche Biomédicale des Armées, Antenne de La Tronche (France); Boudry, Isabelle; Mouret, Stéphane; Wartelle, Julien; Emorine, Sandy; Bertoni, Marine [Département de Toxicologie et Risques Chimiques, Unité de Brûlure Chimique, Institut de Recherche Biomédicale des Armées, Antenne de La Tronche (France); Bérard, Izabel [Laboratoire «Lésions des Acides Nucléiques», Université Joseph Fourier – Grenoble 1, CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble (France); Cléry-Barraud, Cécile [Département de Toxicologie et Risques Chimiques, Unité de Brûlure Chimique, Institut de Recherche Biomédicale des Armées, Antenne de La Tronche (France); and others

2013-12-15

Sulfur mustard (SM) is a chemical warfare agent that targets skin where it induces large blisters. DNA alkylation is a critical step to explain SM-induced cutaneous symptoms. We determined the kinetics of formation of main SM–DNA adducts and compare it with the development of the SM-induced pathogenesis in skin. SKH-1 mice were exposed to 2, 6 and 60 mg/kg of SM and treated skin was biopsied between 6 h and 21 days. Formation of SM DNA adducts was dose-dependent with a maximum immediately after exposure. However, adducts were persistent and still detectable 21 days post-exposure. The time-dependent formation of DNA adducts was also found to be correlated with the appearance of apoptotic cells. This temporal correlation suggests that these two early events are responsible for the severity of the damage to the skin. Besides, SM–DNA adducts were also detected in areas located next to contaminated zone, thus suggesting that SM diffuses in skin. Altogether, this work provides for the first time a clear picture of SM-induced genotoxicity using DNA adducts as a marker. - Highlights: • Sulfur mustard adducts are formed in DNA after skin exposure. • DNA damage formation is an early event in the pathological process of skin burn. • The amount of SM–DNA adducts is maximal at the earliest time point investigated. • Adducts are still detected 3 weeks after exposure. • Sulfur mustard diffuses in skin especially when large doses are applied.

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

International Nuclear Information System (INIS)

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

2015-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Divya, Sasidharan Padmaja; Wang, Xin; Pratheeshkumar, Poyil; Son, Young-Ok; Roy, Ram Vinod [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Department of Toxicology and Cancer Biology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Kim, Donghern; Dai, Jin [Department of Toxicology and Cancer Biology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Hitron, John Andrew; Wang, Lei [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Department of Toxicology and Cancer Biology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Asha, Padmaja [National Centre for Aquatic Animal Health, Cochin University of Science and Technology, Cochin (India); Shi, Xianglin [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Department of Toxicology and Cancer Biology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Department of Toxicology and Cancer Biology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States)

2015-04-01

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

Local lymph node assay (LLNA) for detection of sensitization capacity of chemicals.

Science.gov (United States)

Gerberick, G Frank; Ryan, Cindy A; Dearman, Rebecca J; Kimber, Ian

2007-01-01

The local lymph node assay (LLNA) is a murine model developed to evaluate the skin sensitization potential of chemicals. The LLNA is an alternative approach to traditional guinea pig methods and in comparison provides important animal welfare benefits. The assay relies on measurement of events induced during the induction phase of skin sensitization, specifically lymphocyte proliferation in the draining lymph nodes which is a hallmark of a skin sensitization response. Since its introduction the LLNA has been the subject of extensive evaluation on a national and international scale, and has been successfully validated and incorporated worldwide into regulatory guidelines. Experience gained in recent years has demonstrated that adherence to published procedures and guidelines for the LLNA (e.g., with respect to dose and vehicle selection) is critical for the successful conduct and eventual interpretation of the data. In addition to providing a robust method for skin sensitization hazard identification, the LLNA has proven very useful in assessing the skin sensitizing potency of test chemicals, and this has provided invaluable information to risk assessors. The primary method to make comparisons of the relative potency of chemical sensitizers is to use linear interpolation to estimate the concentration of chemical required to induce a stimulation index of three relative to concurrent vehicle-treated controls (EC3). In certain situations where there are available less than optimal dose response data a log-linear extrapolation method can be used to estimate an EC3 value which can reduce significantly the need for repeat testing of chemicals. The LLNA, when conducted according to published guidelines, provides a robust method for skin sensitization testing that not only provides reliable hazard identification information but also data necessary for effective risk assessment and risk management.

Infrequent alterations of the P53 gene in rat skin cancers induced by ionising-radiation

International Nuclear Information System (INIS)

Jin, Y.; Burns, F.J.; Garte, S.J.; Hosselet, S.; New York Univ., NY

1996-01-01

Radiation carcinogenesis almost certainly involves multiple genetic alterations. Identification of such genetic alterations would provide information to help understand better the molecular mechanism or radiation carcinogenesis. The energy released by ionizing radiation has the potential to produce DNA strand breaks, major gene deletions or rearrangements, and other base damages. Alterations of the p53 gene, a common tumour suppressor gene altered in human cancers, were examined in radiation-induced rat skin cancers. Genomic DNA from a total of 33rat skin cancers induced by ionizing radiation was examined by Southern blot hybridization for abnormal restriction fragment patterns in the p53 gene. A abnormal p53 restriction pattern was found in one of 16 cancers induced by electron radiation and in one of nine cancers induced by neon ions. The genomic DNA from representative cancers, including the two with an abnormal restriction pattern was further examined by polymerase chain reaction amplification and direct sequencing in exons 5-8 of the p53 gene. The results showed that one restriction fragment length polymorphism (RFLP)-positive cancer induced by electron radiation had a partial gene deletion which was defined approximately between exons 2-8, while none of the other cancers showed sequence changes. Our results indicate that the alterations in the critical binding region of the p53 gene are infrequent in rat skin cancers induced by either electron or neon ion radiation. (Author)

Elucidation of xenobiotic metabolism pathways in human skin and human skin models by proteomic profiling.

Directory of Open Access Journals (Sweden)

Sven van Eijl

Full Text Available BACKGROUND: Human skin has the capacity to metabolise foreign chemicals (xenobiotics, but knowledge of the various enzymes involved is incomplete. A broad-based unbiased proteomics approach was used to describe the profile of xenobiotic metabolising enzymes present in human skin and hence indicate principal routes of metabolism of xenobiotic compounds. Several in vitro models of human skin have been developed for the purpose of safety assessment of chemicals. The suitability of these epidermal models for studies involving biotransformation was assessed by comparing their profiles of xenobiotic metabolising enzymes with those of human skin. METHODOLOGY/PRINCIPAL FINDINGS: Label-free proteomic analysis of whole human skin (10 donors was applied and analysed using custom-built PROTSIFT software. The results showed the presence of enzymes with a capacity for the metabolism of alcohols through dehydrogenation, aldehydes through dehydrogenation and oxidation, amines through oxidation, carbonyls through reduction, epoxides and carboxylesters through hydrolysis and, of many compounds, by conjugation to glutathione. Whereas protein levels of these enzymes in skin were mostly just 4-10 fold lower than those in liver and sufficient to support metabolism, the levels of cytochrome P450 enzymes were at least 300-fold lower indicating they play no significant role. Four epidermal models of human skin had profiles very similar to one another and these overlapped substantially with that of whole skin. CONCLUSIONS/SIGNIFICANCE: The proteomics profiling approach was successful in producing a comprehensive analysis of the biotransformation characteristics of whole human skin and various in vitro skin models. The results show that skin contains a range of defined enzymes capable of metabolising different classes of chemicals. The degree of similarity of the profiles of the in vitro models indicates their suitability for epidermal toxicity testing. Overall, these

Liposomalization of oxaliplatin induces skin accumulation of it, but negligible skin toxicity.

Science.gov (United States)

Nishida, Kentaro; Kashiwagi, Misaki; Shiba, Shunsuke; Muroki, Kiwamu; Ohishi, Akihiro; Doi, Yusuke; Ando, Hidenori; Ishida, Tatsuhiro; Nagasawa, Kazuki

2017-12-15

Liposomalization causes alteration of the pharmacokinetics of encapsulated drugs, and allows delivery to tumor tissues through passive targeting via an enhanced permeation and retention (EPR) effect. PEGylated liposomal doxorubicin (Doxil ® , Lipo-DXR), a representative liposomal drug, is well-known to reduce cardiotoxicity and increase the anti-tumor activity of DXR, but to induce the hand-foot syndrome (HFS) as a result of skin DXR accumulation, which is one of its severe adverse effects. We have developed a new liposomal preparation of oxaliplatin (l-OHP), an important anti-tumor drug for treatment of colorectal cancer, using PEGylated liposomes (Lipo-l-OHP), and showed that Lipo-l-OHP exhibits increased anti-tumor activity in tumor-bearing mice compared to the original preparation of l-OHP. However, whether Lipo-l-OHP causes HFS-like skin toxicity similar to Lipo-DXR remains to be determined. Administration of Lipo-l-OHP promoted accumulation of platinum in rat hind paws, however, it caused negligible morphological and histological alterations on the plantar surface of the paws. Administration of DiI-labeled empty PEGylated liposomes gave almost the same distribution profile of dyes into the dermis of hind paws with DXR as in the case of Lipo-DXR. Treatment with Lipo-l-OHP, Lipo-DXR, DiI-labeled empty PEGylated liposomes or empty PEGylated liposomes caused migration of CD68 + macrophages into the dermis of hind paws. These findings suggest that the skin toxicity on administration of liposomalized drugs is reflected in the proinflammatory characteristics of encapsulated drugs, and indicate that Lipo-l-OHP with a higher anti-cancer effect and no HFS may be an outstanding l-OHP preparation leading to an improved quality of life of cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Skin sensitisation: the Colipa strategy for developing and evaluating non-animal test methods for risk assessment.

Science.gov (United States)

Maxwell, Gavin; Aeby, Pierre; Ashikaga, Takao; Bessou-Touya, Sandrine; Diembeck, Walter; Gerberick, Frank; Kern, Petra; Marrec-Fairley, Monique; Ovigne, Jean-Marc; Sakaguchi, Hitoshi; Schroeder, Klaus; Tailhardat, Magali; Teissier, Silvia; Winkler, Petra

2011-01-01

Allergic contact dermatitis is a delayed-type hypersensitivity reaction induced by small reactive chemicals (haptens). Currently, the sensitising potential and potency of new chemicals is usually characterised using data generated via animal studies, such as the local lymph node assay (LLNA). There are, however, increasing public and political concerns regarding the use of animals for the testing of new chemicals. Consequently, the development of in vitro, in chemico or in silico models for predicting the sensitising potential and/or potency of new chemicals is receiving widespread interest. The Colipa Skin Tolerance task force currently collaborates with and/or funds several academic research groups to expand our understanding of the molecular and cellular events occurring during the acquisition of skin sensitisation. Knowledge gained from this research is being used to support the development and evaluation of novel alternative approaches for the identification and characterisation of skin sensitizing chemicals. At present three non-animal test methods (Direct Peptide Reactivity Assay (DPRA), Myeloid U937 Skin Sensitisation Test (MUSST) and human Cell Line Activation Test (hCLAT)) have been evaluated in Colipa interlaboratory ring trials for their potential to predict skin sensitisation potential and were recently submitted to ECVAM for formal pre-validation. Data from all three test methods will now be used to support the study and development of testing strategy approaches for skin sensitiser potency prediction. This publication represents the current viewpoint of the cosmetics industry on the feasibility of replacing the need for animal test data for informing skin sensitisation risk assessment decisions.

Improvement effect of corn silk, perilla leaf and grape stem extract mixture against UVB-induced skin damage and compound 48/80-induced pruritus

Energy Technology Data Exchange (ETDEWEB)

Cho, Byoung Ok; Shin, Jae Young; Che, Denis Nchang; Hwang, Young Min; Lee, Hyun Seo; Choi, Ji Won; Jang, Seon Il [Jeonju University, Jeonju (Korea, Republic of); Ryu, Cheol [Hyangmiwon Corporation, Gimje (Korea, Republic of)

2017-02-15

This study was conducted to evaluate the synergistic protective effects of mixtures of corn silk, perilla leaf and grape stem extract (CPG mixture) against UVB-induced skin damage and compound 48/80-induced pruritus in mice. The results showed that treatment with CPG mixture exhibited much stronger suppressive effect on erythema and melanin index as well as melanin formation than treatment with ascorbic acid (AA) in UVB-irradiated mice. Moreover, the treatment with CPG mixture showed ameliorative effect on immune cell infiltration and collagen fiber destruction in UV-irradiated mice. The treatment with CPG mixture inhibited glutathione (GSH) depletion, lipid peroxidation and production of pro-inflammatory cytokines in UVB-irradiated mice. Furthermore, the treatment with CPG mixture inhibited compound 48/80-induced scratching behavior and histological changes in mice. Taken together, these results indicated that CPG mixture has potentials as functional and therapeutic materials against skin damage and itch-related skin diseases.

Improvement effect of corn silk, perilla leaf and grape stem extract mixture against UVB-induced skin damage and compound 48/80-induced pruritus

International Nuclear Information System (INIS)

Cho, Byoung Ok; Shin, Jae Young; Che, Denis Nchang; Hwang, Young Min; Lee, Hyun Seo; Choi, Ji Won; Jang, Seon Il; Ryu, Cheol

2017-01-01

This study was conducted to evaluate the synergistic protective effects of mixtures of corn silk, perilla leaf and grape stem extract (CPG mixture) against UVB-induced skin damage and compound 48/80-induced pruritus in mice. The results showed that treatment with CPG mixture exhibited much stronger suppressive effect on erythema and melanin index as well as melanin formation than treatment with ascorbic acid (AA) in UVB-irradiated mice. Moreover, the treatment with CPG mixture showed ameliorative effect on immune cell infiltration and collagen fiber destruction in UV-irradiated mice. The treatment with CPG mixture inhibited glutathione (GSH) depletion, lipid peroxidation and production of pro-inflammatory cytokines in UVB-irradiated mice. Furthermore, the treatment with CPG mixture inhibited compound 48/80-induced scratching behavior and histological changes in mice. Taken together, these results indicated that CPG mixture has potentials as functional and therapeutic materials against skin damage and itch-related skin diseases

Dry skin - self-care

Science.gov (United States)

... pat skin dry then apply your moisturizer. Avoid skin care products and soaps that contain alcohol, fragrances, dyes, or other chemicals. Take short, warm baths or showers. Limit your ... gentle skin cleansers or soap with added moisturizers. Only use ...

Ultraviolet Radiation-Induced Cytogenetic Damage in White, Hispanic and Black Skin Melanocytes: A Risk for Cutaneous Melanoma

Energy Technology Data Exchange (ETDEWEB)

Dasgupta, Amrita [Hampton University Skin of Color Research Institute, Hampton, VA 23668 (United States); Katdare, Meena, E-mail: mkatdare@gmail.com [Hampton University Skin of Color Research Institute, Hampton, VA 23668 (United States); Department of Dermatology, Eastern Virginia Medical School, Norfolk, VA 23507 (United States)

2015-08-14

Cutaneous Melanoma (CM) is a leading cause of cancer deaths, with reports indicating a rising trend in the incidence rate of melanoma among Hispanics in certain U.S. states. The level of melanin pigmentation in the skin is suggested to render photoprotection from the DNA-damaging effects of Ultraviolet Radiation (UVR). UVR-induced DNA damage leads to cytogenetic defects visualized as the formation of micronuclei, multinuclei and polymorphic nuclei in cells, and a hallmark of cancer risk. The causative relationship between Sun exposure and CM is controversial, especially in Hispanics and needs further evaluation. This study was initiated with melanocytes from White, Hispanic and Black neonatal foreskins which were exposed to UVR to assess their susceptibility to UVR-induced modulation of cellular growth, cytogenetic damage, intracellular and released melanin. Our results show that White and Hispanic skin melanocytes with similar levels of constitutive melanin are susceptible to UVR-induced cytogenetic damage, whereas Black skin melanocytes are not. Our data suggest that the risk of developing UVR-induced CM in a skin type is correlated with the level of cutaneous pigmentation and its ethnic background. This study provides a benchmark for further investigation on the damaging effects of UVR as risk for CM in Hispanics.

Ultraviolet Radiation-Induced Cytogenetic Damage in White, Hispanic and Black Skin Melanocytes: A Risk for Cutaneous Melanoma

International Nuclear Information System (INIS)

Dasgupta, Amrita; Katdare, Meena

2015-01-01

Cutaneous Melanoma (CM) is a leading cause of cancer deaths, with reports indicating a rising trend in the incidence rate of melanoma among Hispanics in certain U.S. states. The level of melanin pigmentation in the skin is suggested to render photoprotection from the DNA-damaging effects of Ultraviolet Radiation (UVR). UVR-induced DNA damage leads to cytogenetic defects visualized as the formation of micronuclei, multinuclei and polymorphic nuclei in cells, and a hallmark of cancer risk. The causative relationship between Sun exposure and CM is controversial, especially in Hispanics and needs further evaluation. This study was initiated with melanocytes from White, Hispanic and Black neonatal foreskins which were exposed to UVR to assess their susceptibility to UVR-induced modulation of cellular growth, cytogenetic damage, intracellular and released melanin. Our results show that White and Hispanic skin melanocytes with similar levels of constitutive melanin are susceptible to UVR-induced cytogenetic damage, whereas Black skin melanocytes are not. Our data suggest that the risk of developing UVR-induced CM in a skin type is correlated with the level of cutaneous pigmentation and its ethnic background. This study provides a benchmark for further investigation on the damaging effects of UVR as risk for CM in Hispanics

Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model.

Science.gov (United States)

Choi, Hyunjung; Shin, Ji Hyun; Kim, Eun Sung; Park, So Jung; Bae, Il-Hong; Jo, Yoon Kyung; Jeong, In Young; Kim, Hyoung-June; Lee, Youngjin; Park, Hea Chul; Jeon, Hong Bae; Kim, Ki Woo; Lee, Tae Ryong; Cho, Dong-Hyung

2016-01-01

The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH)-smoothened (Smo) signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.

Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model.

Directory of Open Access Journals (Sweden)

Hyunjung Choi

Full Text Available The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH-smoothened (Smo signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.

Photoprotection of Buddleja cordata extract against UVB-induced skin damage in SKH-1 hairless mice.

Science.gov (United States)

Avila Acevedo, José Guillermo; Espinosa González, Adriana Montserrat; De Maria y Campos, Diana Matamoros; Benitez Flores, José del Carmen; Hernández Delgado, Tzasna; Flores Maya, Saul; Campos Contreras, Jorge; Muñoz López, José Luis; García Bores, Ana María

2014-08-03

In recent years, there has been considerable interest in using botanical agents to prevent skin damage resulting from solar UV-irradiation. Buddleja cordata is a plant that is known as "tepozan". Some people in Mexico use the leaves of this plant to treat tumours, abscesses, sores and burns. The purpose of this study is to investigate the photoprotective properties of Buddleja cordata methanolic extract (BCME) against UVB-induced skin damage in SKH-1 hairless mice at the macroscopic and histological levels. BCME was characterised to determine its spectroscopic, chromatographic and antioxidant (DPPH, superoxide and hydroxyl radicals) properties. To conduct the photoprotection studies, BCME was applied topically to the skin of SKH-1 mice before acute exposure to UVB for 10 minutes. The murine skin samples were used for macroscopic and histological studies to assess tissue damage. Penetration of active components of BCME into stratum corneum on the dorsal area of mice was investigated in vivo by the tape stripping method. Moreover, genotoxicity of BCME was evaluated in a Vicia faba cell root micronucleus model. BCME displayed absorbance over the entire UVB spectrum, and its principal components included verbascoside and linarin. BCME exhibited antioxidant activity and significantly scavenged hydroxyl radicals. BCME reduced erythema, sunburn cell production, vessel congestion and epidermal thickening of UVB irradiated mouse skin. BCME penetrate the skin of mice. BCME did not exhibit genotoxic activity in the micronucleus test. The topical administration of BCME protected against acute UVB-induced damage in mouse SKH-1 skin, and our results suggest that BCME may potentially prevent photodamage.

Development and Characterization of VEGF165-Chitosan Nanoparticles for the Treatment of Radiation-Induced Skin Injury in Rats

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Daojiang Yu

2016-10-01

Full Text Available Radiation-induced skin injury, which remains a serious concern in radiation therapy, is currently believed to be the result of vascular endothelial cell injury and apoptosis. Here, we established a model of acute radiation-induced skin injury and compared the effect of different vascular growth factors on skin healing by observing the changes of microcirculation and cell apoptosis. Vascular endothelial growth factor (VEGF was more effective at inhibiting apoptosis and preventing injury progression than other factors. A new strategy for improving the bioavailability of vascular growth factors was developed by loading VEGF with chitosan nanoparticles. The VEGF-chitosan nanoparticles showed a protective effect on vascular endothelial cells, improved the local microcirculation, and delayed the development of radioactive skin damage.

Membrane damage induced in cultured human skin fibroblasts by UVA irradiation

International Nuclear Information System (INIS)

Gaboriau, F.; Morliere, P.; Marquis, I.; Moysan, A.; Geze, M.; Dubertret, L.

1993-01-01

Irradiation of cultured human skin fibroblasts with ultraviolet light from 320 to 400 nm (UVA) leads to a decrease in the membrane fluidity exemplified by an enhanced fluorescence anisotropy of the lipophilic fluorescent probe 1-[4-trimethylamino)-phenyl]-6-phenylhexa-1,3,5-triene. This UVA-induced decrease in fluidity is associated with lactate dehydrogenase leakage in the supernatant. Vitamin E, an inhibitor of lipid peroxidation, exerts a protective effect on both phenomena. Therefore, this UVA-induced damage in membrane properties may be related to lipid peroxidation processes. Moreover, exponentially growing cells are more sensitive to these UVA-induced alterations than confluent cells. (Author)

Full-thickness human skin explants for testing the toxicity of topically applied chemicals

International Nuclear Information System (INIS)

Nakamura, M.; Rikimaru, T.; Yano, T.; Moore, K.G.; Pula, P.J.; Schofield, B.H.; Dannenberg, A.M. Jr.

1990-01-01

This report describes a model organ-culture system for testing the toxicity of chemical substances that are topically applied to human skin. In this system, the viable keratinocytes in the full-thickness skin explants are protected by the same keratinized layer as skin remaining on the donor, and toxicity can be assessed microscopically and/or biochemically. The human skin specimens were discards from a variety of surgical procedures. They were cut into full-thickness 1.0-cm2 explants, and briefly exposed to the military vesicant sulfur mustard (SM), which was used as a model toxicant. The explants were then organ cultured in small Petri dishes for 24 h at 36 degrees C. In the 0.03-1.0% dosage range, a straight-line dose-response relationship occurred between the concentration of SM applied and the number of paranuclear vacuoles seen histologically in the epidermis. Within the same SM dosage range, there was also a proportional decrease in 14C-leucine incorporation by the explants. Thus, the number of paranuclear vacuoles reflected decreases in protein synthesis by the injured epidermal cells. The epidermis of full-thickness untreated (control) human skin explants usually remained viable for 7 d when stored at 4 degrees C in culture medium. During storage, a relatively small number of paranuclear vacuoles developed within the epidermis, but the explants were still quite satisfactory for testing SM toxicity. Incubation (for 4 or 24 h at 36 degrees C) of such control skin explants reduced (often by 50%) the small number of paranuclear vacuoles produced during 4-7 d of storage. This reduction was probably caused by autolysis of many of the vacuolated cells. Two types of paranuclear vacuoles could be identified by both light and electron microscopy: a storage type and a toxicant type. The storage type seemed to be caused by autolysis of cell components

Full-thickness human skin explants for testing the toxicity of topically applied chemicals

Energy Technology Data Exchange (ETDEWEB)

Nakamura, M.; Rikimaru, T.; Yano, T.; Moore, K.G.; Pula, P.J.; Schofield, B.H.; Dannenberg, A.M. Jr. (Johns Hopkins Univ., Baltimore, MD (USA))

1990-09-01

This report describes a model organ-culture system for testing the toxicity of chemical substances that are topically applied to human skin. In this system, the viable keratinocytes in the full-thickness skin explants are protected by the same keratinized layer as skin remaining on the donor, and toxicity can be assessed microscopically and/or biochemically. The human skin specimens were discards from a variety of surgical procedures. They were cut into full-thickness 1.0-cm2 explants, and briefly exposed to the military vesicant sulfur mustard (SM), which was used as a model toxicant. The explants were then organ cultured in small Petri dishes for 24 h at 36 degrees C. In the 0.03-1.0% dosage range, a straight-line dose-response relationship occurred between the concentration of SM applied and the number of paranuclear vacuoles seen histologically in the epidermis. Within the same SM dosage range, there was also a proportional decrease in 14C-leucine incorporation by the explants. Thus, the number of paranuclear vacuoles reflected decreases in protein synthesis by the injured epidermal cells. The epidermis of full-thickness untreated (control) human skin explants usually remained viable for 7 d when stored at 4 degrees C in culture medium. During storage, a relatively small number of paranuclear vacuoles developed within the epidermis, but the explants were still quite satisfactory for testing SM toxicity. Incubation (for 4 or 24 h at 36{degrees}C) of such control skin explants reduced (often by 50%) the small number of paranuclear vacuoles produced during 4-7 d of storage. This reduction was probably caused by autolysis of many of the vacuolated cells. Two types of paranuclear vacuoles could be identified by both light and electron microscopy: a storage type and a toxicant type. The storage type seemed to be caused by autolysis of cell components.

Treatment of silymarin, a plant flavonoid, prevents ultraviolet light-induced immune suppression and oxidative stress in mouse skin.

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Katiyar, Santosh K

2002-12-01

It is well documented that ultraviolet (UV) light-induced immune suppression and oxidative stress play an important role in the induction of skin cancers. Earlier, we have shown that topical treatment of silymarin, a plant flavonoid from milk thistle (Silybum marianum L. Gaertn.), to mouse skin prevents photocarcinogenesis, but the preventive mechanism of photocarcinogenesis in vivo animal system by silymarin is not well defined and understood. To define the mechanism of prevention, we employed immunostaining, analytical assays and ELISA which revealed that topical treatment of silymarin (1 mg/cm2 skin area) to C3H/HeN mice inhibits UVB (90 mJ/cm2)-induced suppression of contact hypersensitivity (CHS) response to contact sensitizer dinitrofluorobenzene. Prevention of UVB-induced suppression of CHS by silymarin was found to be associated with the inhibition of infiltrating leukocytes, particularly CD11b+ cell type, and myeloperoxidase activity (50-71%). Silymarin treatment also resulted in significant reduction of UVB-induced immunosuppressive cytokine interleukin-10 producing cells and its production (58-72%, pskin cancer risk human population and ii) development of sunscreen containing silymarin as an antioxidant (chemopreventive agent) or silymarin can be supplemented in skin care products.

The effect of Mepitel Film on acute radiation-induced skin reactions in head and neck cancer patients: a feasibility study.

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Wooding, Hayley; Yan, Jing; Yuan, Ling; Chyou, Te-Yu; Gao, Shanbao; Ward, Iain; Herst, Patries M

2018-01-01

Mepitel Film significantly decreases acute radiation-induced skin reactions in breast cancer patients. Here we investigated the feasibility of using Mepitel Film in head and neck cancer patients (ACTRN12614000932662). Out of a total of 36 head and neck cancer patients from New Zealand (NZ) (n = 24) and China (n = 12) recruited between June 2015 and December 2016, 33 patients complied with protocol. Of these, 11 NZ patients followed a management protocol; 11 NZ patients and 11 Chinese patients followed a prophylactic protocol. An area of the neck receiving a homogenous radiation dose of > 35 Gy was divided into two equal halves; one half was randomized to Film and the other to either Sorbolene cream (NZ) or Biafine cream (China). Skin reaction severity was measured by Radiation Induced Skin Reaction Assessment Scale and expanded Radiation Therapy Oncology Group toxicity criteria. Skin dose was measured by thermoluminescent dosimeters or gafchromic film. Film decreased overall skin reaction severity (combined Radiation Induced Skin Reaction Assessment Scale score) by 29% and moist desquamation rates by 37% in the Chinese cohort and by 27 and 28%, respectively in the NZ cohort. Mepitel Film did not affect head movements but did not adhere well to the skin, particularly in males with heavy beard stubble, and caused itchiness, particularly in Chinese patients. Mepitel Film reduced acute radiation-induced skin reactions in our head and neck cancer patients, particularly in patients without heavy stubble. Advances in knowledge: This is the first study to confirm the feasibility of using Mepitel Film in head and neck cancer patients.

Development of an Active Topical Skin Protectant (aTSP)

Science.gov (United States)

2016-02-01

protectant as a follow-on product to Skin Exposure Reduction Paste Against Chemical Warfare Agents (SERPACWA). 15. SUBJECT TERMS decontamination , Skin...corresponding author), Chemical Warfare Agent Decontamination from Skin, In J.A. Romano Jr., B.J. Lukey, and H. Salem, eds., 2nd Edition of Chemical Warfare ...CG, and Braue, EH Jr (corresponding author), “ Chemical warfare agent decontamination from skin,” In J.A. Romano Jr., B.J. Lukey, and H. Salem

Blebbistatin, a myosin II inhibitor, suppresses Ca(2+)-induced and "sensitized"-contraction of skinned tracheal muscles from guinea pig.

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Yumoto, Masatoshi; Watanabe, Masaru

2013-01-01

Blebbistatin, a potent inhibitor of myosin II, has inhibiting effects on Ca(2+)-induced contraction and contractile filament organization without affecting the Ca(2+)-sensitivity to the force and phosphorylation level of myosin regulatory light chain (MLC20) in skinned (cell membrane permeabilized) taenia cecum from the guinea pig (Watanabe et al., Am J Physiol Cell Physiol. 2010; 298: C1118-26). In the present study, we investigated blebbistatin effects on the contractile force of skinned tracheal muscle, in which myosin filaments organization is more labile than that in the taenia cecum. Blebbistatin at 10 μM or higher suppressed Ca(2+)-induced tension development at any given Ca(2+) concentration, but had little effects on the Ca(2+)- induced myosin light chain phosphorylation. Also blebbistatin at 10 μM and higher significantly suppressed GTP-γS-induced "sensitized" force development. Since the force inhibiting effects of blebbistatin on the skinned trachea were much stronger than those in skinned taenia cecum, blebbistatin might directly affect myosin filaments organization.

Use of silicon for skin and hair care: an approach of chemical forms available and efficacy*

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de Araújo, Lidiane Advincula; Addor, Flavia; Campos, Patrícia Maria Berardo Gonçalves Maia

2016-01-01

Silicon is the second most abundant element on Earth, and the third most abundant trace element in human body. It is present in water, plant and animal sources. On the skin, it is suggested that silicon is important for optimal collagen synthesis and activation of hydroxylating enzymes, improving skin strength and elasticity. Regarding hair benefits, it was suggested that a higher silicon content in the hair results in a lower rate of hair loss and increased brightness. For these beneficial effects, there is growing interest in scientific studies evaluating the efficacy and safety of using dietary supplements containing silicon. Its use aims at increasing blood levels of this element and improving the skin and its annexes appearance. There are different forms of silicon supplements available and the most important consideration to be made in order to select the best option is related to safety and bioavailability. Silicon supplements are widely used, though there is wide variation in silicon bioavailability, ranging from values below 1% up to values close to 50%, depending on the chemical form. Therefore, the aim of this study was to evaluate the scientific literature related to the different chemical forms of silicon supplements available and the limitations and recent progress in this field. According to reported studies, among the different chemical forms available, the orthosilicic acid (OSA) presents the higher bioavailability, whereas the others forms have absorption inversely proportional to the degree of polymerization. However, clinical studies evaluating safety and efficacy are still lacking. PMID:27438201

UVB-induced gene expression in the skin of Xiphophorus maculatus Jp 163 B☆

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Yang, Kuan; Boswell, Mikki; Walter, Dylan J.; Downs, Kevin P.; Gaston-Pravia, Kimberly; Garcia, Tzintzuni; Shen, Yingjia; Mitchell, David L.; Walter, Ronald B.

2014-01-01

Xiphophorus fish and interspecies hybrids represent long-standing models to study the genetics underlying spontaneous and induced tumorigenesis. The recent release of the Xiphophorus maculatus genome sequence will allow global genetic regulation studies of genes involved in the inherited susceptibility to UVB-induced melanoma within select backcross hybrids. As a first step toward this goal, we report results of an RNA-Seq approach to identify genes and pathways showing modulated transcription within the skin of X. maculatus Jp 163 B upon UVB exposure. X. maculatus Jp 163 B were exposed to various doses of UVB followed by RNA-Seq analysis at each dose to investigate overall gene expression in each sample. A total of 357 genes with a minimum expression change of 4-fold (p-adj fish skin to UVB exposure. PMID:24556253

An Animal Model of Trichloroethylene-Induced Skin Sensitization in BALB/c Mice.

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Wang, Hui; Zhang, Jia-xiang; Li, Shu-long; Wang, Feng; Zha, Wan-sheng; Shen, Tong; Wu, Changhao; Zhu, Qi-xing

2015-01-01

Trichloroethylene (TCE) is a major occupational hazard and environmental contaminant that can cause multisystem disorders in the form of occupational medicamentosa-like dermatitis. Development of dermatitis involves several proinflammatory cytokines, but their role in TCE-mediated dermatitis has not been examined in a well-defined experimental model. In addition, few animal models of TCE sensitization are available, and the current guinea pig model has apparent limitations. This study aimed to establish a model of TCE-induced skin sensitization in BALB/c mice and to examine the role of several key inflammatory cytokines on TCE sensitization. The sensitization rate of dorsal painted group was 38.3%. Skin edema and erythema occurred in TCE-sensitized groups, as seen in 2,4-dinitrochlorobenzene (DNCB) positive control. Trichloroethylene sensitization-positive (dermatitis [+]) group exhibited increased thickness of epidermis, inflammatory cell infiltration, swelling, and necrosis in dermis and around hair follicle, but ear painted group did not show these histological changes. The concentrations of serum proinflammatory cytokines including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-2 were significantly increased in 24, 48, and 72 hours dermatitis [+] groups treated with TCE and peaked at 72 hours. Deposition of TNF-α, IFN-γ, and IL-2 into the skin tissue was also revealed by immunohistochemistry. We have established a new animal model of skin sensitization induced by repeated TCE stimulations, and we provide the first evidence that key proinflammatory cytokines including TNF-α, IFN-γ, and IL-2 play an important role in the process of TCE sensitization. © The Author(s) 2015.

Occupational skin hazards and prevalence of occupational skin diseases in shoe manufacturing workers in Indonesia.

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Febriana, Sri Awalia; Soebono, Hardyanto; Coenraads, Pieter-Jan

2014-02-01

Shoe manufacturing workers are exposed daily to an extensive range of potential physical and chemical occupational hazards. Shoe manufacturing in Indonesia is one of the industrial sectors that has shown sustained growth amongst the newly industrialized countries (NICs). In this study, we investigated the possible potential exposure of the workers to physical and occupational hazards and determined the prevalence of occupational skin diseases at a shoe manufacturing factory in Indonesia. A cross-sectional study on the observation of the working process and an inventory and risk assessment of exposure to the chemicals used. Classification of chemicals as potential sensitizers/irritants and qualitative assessments of these chemicals were done. Workers were examined and interviewed using the Nordic Occupational Skin Questionnaire-2002/LONG. The risk of Occupational skin diseases (OSD) at the shoe factory was mainly related to the exposure of the workers' skin to potential physical and chemical hazards in hot and humid environmental conditions. From a total of 514 workers, 8.5 % reported current OSD and 4.8 % reported a history of OSD. Occupational skin diseases were diagnosed in 29 % of the workers by dermatologists and 7.6 % had an occupational contact dermatitis (OCD). Of the 39 workers with contact dermatitis, 33 consented to being patch tested, 14 (3 %) workers showed a positive results and considered as having an occupational allergic contact dermatitis (OACD) and 25 (4.9 %) had an occupational irritant contact dermatitis (OICD). We observed a repeated and prolonged exposure of the workers to numerous physical and chemical skin hazards at this factory.

Poly-MVA attenuates 7,12- dimethylbenz[a]anthracene initiated and croton oil promoted skin papilloma formation on mice skin.

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Veena, Ravindran K; Ajith, Thekkuttuparambil A; Janardhanan, Kainoor K; Antonawich, Francis

2017-09-01

Chemopreventive agents which exhibit activities such as anti-inflammation, inhibition of carcinogen induced mutagenesis and scavenging of free radical might play a decisive role in the inhibition of chemical carcinogenesis either at the initiation or promotion stage. Many synthesized palladium (Pd) complexes tested experimentally for antitumor activity are found effective. Poly-MVA is a liquid blend preparation containing B complex vitamins, ruthenium with Pd complexed with alpha lipoic acid as the major ingredients. The antitumor effect of Poly-MVA was evaluated against 7,12-dimethylbenz[a] anthracene-initiated croton oil-promoted papilloma formation on mice skin. Skin tumor was initiated with a single application of 390 nmol of DMBA in 20 µl acetone. The effect of Poly-MVA against croton oil- induced inflammation and lipid peroxidation on the mice skin was also evaluated. Topical application of Poly-MVA (100 µl, twice weekly for 18 weeks) 30 minutes prior to each croton oil application, significantly decreased the tumor incidence (11%) and the average number of tumor per animals. Application of Poly-MVA (100 µl) before croton oil significantly (p < 0.05) protected the mouse skin from inflammation (36%) and lipid peroxidation (14%) when compared to the croton oil alone treated group. Experimental results indicate that Poly-MVA attenuate the tumor promoting effects of croton oil and the effect may probably be due to its anti-inflammatory and antioxidant activity.

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

Science.gov (United States)

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

2016-07-01

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

Selenium inhibits UV-light-induced skin carcinogenesis in hairless mice

International Nuclear Information System (INIS)

Overvad, Kim; Thorling, E.B.; Bjerring, Peter; Ebbesen, Peter

1985-01-01

Female hairless inbred hr/hr mice were exposed to UV-B irradiation from Philips TL 40W/13 fluorescent tubes. Fractionated irradiation, given as single daily doses 5 days a week, was gradually increased from 0.04 to 0.4 J/cm 2 over 2 weeks. Irradiation at 0.4 J/cm 2 was continued for 20 weeks. Selenium supplementation given as sodium selenite in the drinking water at 2, 4 and 8 mg/l began 3 weeks before UV-irradiation and continued thereafter. Development of skin tumors was followed by weekly examinations. Statistical analyses revealed significant dose-dependent selenium-mediated protection against UV-light-induced skin cancer. Leukemia developed in 5 of 150 UV-irradiated mice as opposed to none in a group of 60 unirradiated mice. (author)

Inhibition of bcl-2 and cox-2 Protein Expression after Local Application of a New Carmustine-Loaded Clinoptilolite-Based Delivery System in a Chemically Induced Skin Cancer Model in Mice

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Cristina Mihaela Ghiciuc

2017-11-01

Full Text Available Our research has focused on in vitro and in vivo evaluations of a new Carmustine (BCNU-loaded clinoptilolite-based delivery system. Two clinoptilolite ionic forms—hydrogen form (HCLI and sodium form (NaCLI—were prepared, allowing a loading degree of about 5–6 mg BCNU/g of zeolite matrix due to the dual porous feature of clinoptilolite. Clinoptilolite-based delivery systems released 35.23% of the load in 12 h for the BCNU@HCLI system and only 10.82% for the BCNU@NaCLI system. The BCNU@HCLI system was chosen to develop gel and cream semisolid dosage forms. The cream (C_BCNU@HCLI released 29.6% of the loaded BCNU after 12 h in the Nylon synthetic membrane test and 31.6% in the collagen membrane test, higher by comparison to the gel. The new cream was evaluated in vivo in a chemically induced model of skin cancer in mice. Quantitative immunohistochemistry analysis showed stronger inhibition of B-cell lymphoma-2 (bcl-2 and cyclooxygenase 2 (cox-2 protein expression, known markers for cancer survival and aggressiveness, after the treatment with C_BCNU@HCLI by comparison to all the control treatment types, including an off-label magistral formula commercially available Carmustine cream as reference, bringing evidence that a clinoptilolite-based delivery systems could be used as a cancer drug carriers and controlled release systems (skin-targeted topical delivery systems.

An in vitro method for detecting chemical sensitization using human reconstructed skin models and its applicability to cosmetic, pharmaceutical, and medical device safety testing.

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McKim, James M; Keller, Donald J; Gorski, Joel R

2012-12-01

Chemical sensitization is a serious condition caused by small reactive molecules and is characterized by a delayed type hypersensitivity known as allergic contact dermatitis (ACD). Contact with these molecules via dermal exposure represent a significant concern for chemical manufacturers. Recent legislation in the EU has created the need to develop non-animal alternative methods for many routine safety studies including sensitization. Although most of the alternative research has focused on pure chemicals that possess reasonable solubility properties, it is important for any successful in vitro method to have the ability to test compounds with low aqueous solubility. This is especially true for the medical device industry where device extracts must be prepared in both polar and non-polar vehicles in order to evaluate chemical sensitization. The aim of this research was to demonstrate the functionality and applicability of the human reconstituted skin models (MatTek Epiderm(®) and SkinEthic RHE) as a test system for the evaluation of chemical sensitization and its potential use for medical device testing. In addition, the development of the human 3D skin model should allow the in vitro sensitization assay to be used for finished product testing in the personal care, cosmetics, and pharmaceutical industries. This approach combines solubility, chemical reactivity, cytotoxicity, and activation of the Nrf2/ARE expression pathway to identify and categorize chemical sensitizers. Known chemical sensitizers representing extreme/strong-, moderate-, weak-, and non-sensitizing potency categories were first evaluated in the skin models at six exposure concentrations ranging from 0.1 to 2500 µM for 24 h. The expression of eight Nrf2/ARE, one AhR/XRE and two Nrf1/MRE controlled gene were measured by qRT-PCR. The fold-induction at each exposure concentration was combined with reactivity and cytotoxicity data to determine the sensitization potential. The results demonstrated that

Protective Effects of Soy Oligopeptides in Ultraviolet B-Induced Acute Photodamage of Human Skin

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Bing-rong Zhou

2016-01-01

Full Text Available Aim. We explored the effects of soy oligopeptides (SOP in ultraviolet B- (UVB- induced acute photodamage of human skin in vivo and foreskin ex vivo. Methods. We irradiated the forearm with 1.5 minimal erythemal dose (MED of UVB for 3 consecutive days, establishing acute photodamage of skin, and topically applied SOP. Erythema index (EI, melanin index, stratum corneum hydration, and transepidermal water loss were measured by using Multiprobe Adapter 9 device. We irradiated foreskin ex vivo with the same dose of UVB (180 mJ/cm2 for 3 consecutive days and topically applied SOP. Sunburn cells were detected by using hematoxylin and eosin staining. Apoptotic cells were detected by using terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Cyclobutane pyrimidine dimers (CPDs, p53 protein, Bax protein, and Bcl-2 protein were detected by using immunohistochemical staining. Results. Compared with UVB group, UVB-irradiated skin with topically applied SOP showed significantly decreased EI. Compared with UVB group, topical SOP significantly increased Bcl-2 protein expression and decreased CPDs-positive cells, sunburn cells, apoptotic cells, p53 protein expression, and Bax protein expressions in the epidermis of UVB-irradiated foreskin. Conclusion. Our study demonstrated that topical SOP can protect human skin against UVB-induced photodamage.

Biodegradable Polymers Induce CD54 on THP-1 Cells in Skin Sensitization Test.

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Jung, Yeon Suk; Kato, Reiko; Tsuchiya, Toshie

2011-01-01

Currently, nonanimal methods of skin sensitization testing for various chemicals, biodegradable polymers, and biomaterials are being developed in the hope of eliminating the use of animals. The human cell line activation test (h-CLAT) is a skin sensitization assessment that mimics the functions of dendritic cells (DCs). DCs are specialized antigen-presenting cells, and they interact with T cells and B cells to initiate immune responses. Phenotypic changes in DCs, such as the production of CD86 and CD54 and internalization of MHC class II molecules, have become focal points of the skin sensitization test. In this study, we used h-CLAT to assess the effects of biodegradable polymers. The results showed that several biodegradable polymers increased the expression of CD54, and the relative skin sensitizing abilities of biodegradable polymers were PLLG (75 : 25) < PLLC (40 : 60) < PLGA (50 : 50) < PCG (50 : 50). These results may contribute to the creation of new guidelines for the use of biodegradable polymers in scaffolds or allergenic hazards.

Biodegradable Polymers Induce CD54 on THP-1 Cells in Skin Sensitization Test

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Yeon Suk Jung

2011-01-01

Full Text Available Currently, nonanimal methods of skin sensitization testing for various chemicals, biodegradable polymers, and biomaterials are being developed in the hope of eliminating the use of animals. The human cell line activation test (h-CLAT is a skin sensitization assessment that mimics the functions of dendritic cells (DCs. DCs are specialized antigen-presenting cells, and they interact with T cells and B cells to initiate immune responses. Phenotypic changes in DCs, such as the production of CD86 and CD54 and internalization of MHC class II molecules, have become focal points of the skin sensitization test. In this study, we used h-CLAT to assess the effects of biodegradable polymers. The results showed that several biodegradable polymers increased the expression of CD54, and the relative skin sensitizing abilities of biodegradable polymers were PLLG (75 : 25 < PLLC (40 : 60 < PLGA (50 : 50 < PCG (50 : 50. These results may contribute to the creation of new guidelines for the use of biodegradable polymers in scaffolds or allergenic hazards.

Biophysical effects of water and synthetic urine on skin.

Science.gov (United States)

Mayrovitz, H N; Sims, N

2001-01-01

Pressure ulcers often occur at sites subjected to pressure and wetness. Although skin wetness is a risk factor for pressure ulcers,the mechanisms and effects of wetness versus urine constituents on skin breakdown is unclear. The hypothesis that wetness reduces skin hardness and, thereby, increases vulnerability of underlying blood vessels to pressure-induced flow reductions was tested in this study. Pads saturated with water and with a water solution mixed with the main chemical constituents of urine (synthetic urine; s-urine) were applied to forearm skin of 10 healthy subjects for 5.5 hours. Skin hardness, blood flow change caused by 60 mm Hg of pressure, erythema, and temperature were compared among dry, water, and s-urine test sites. 10 healthy women. Research Center, Nova Southeastern University, Health Professions Division, Fort Lauderdale, FL. S-urine and water caused significant reductions in initial hardness and caused greater initial perfusion decreases during pressure load when compared with dry sites. Skin temperature and erythema were lower at wet sites when compared with dry sites. The findings of this study are consistent with the concept that sustained skin wetness increases vulnerability to pressure-induced blood flow reduction. The effect appears to be mainly dependent on wetness, but urine constituents may exacerbate the effect. In addition, wetness-related skin cooling may play a role. In the healthy subjects studied, the blood flow decrease was not sustained due to perfusion recovery under pressure. Skin wetness would likely have more sustained effects in patients with compromised recovery mechanisms. Measures to diminish skin exposure to wetness in these patients, whatever the wetness source, are an important consideration in a multifaceted strategy to reduce the risk of pressure ulcers.

MAPK Phosphatase-1 Deficiency Exacerbates the Severity of Imiquimod-Induced Psoriasiform Skin Disease

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Weiheng Zhao

2018-03-01

Full Text Available Persistent activation of mitogen-activated protein kinase (MAPK is believed to be involved in psoriasis pathogenesis. MAPK phosphatase-1 (MKP-1 is an important negative regulator of MAPK activity, but the cellular and molecular mechanisms of MKP-1 in psoriasis development are largely unknown. In this study, we found that the expression of MKP-1 was decreased in the imiquimod (IMQ-induced psoriasiform mouse skin. MKP-1-deficient (MKP-1−/− mice were highly susceptible to IMQ-induced skin inflammation, which was associated with increased production of inflammatory cytokines and chemokines. MKP-1 acted on both hematopoietic and non-hematopoietic cells to regulate psoriasis pathogenesis. MKP-1 deficiency in macrophages led to enhanced p38 activation and higher expression of interleukin (IL-1β, CXCL2, and S100a8 upon R848 stimulation. Moreover, MKP-1 deficiency in the non-hematopoietic compartments led to an enhanced IL-22 receptor signaling and higher expression of CXCL1 and CXCL2 upon IMQ treatment. Collectively, our data suggest a critical role for MKP-1 in the regulation of skin inflammation.

Vehicle effects on human stratum corneum absorption and skin penetration.

Science.gov (United States)

Zhang, Alissa; Jung, Eui-Chang; Zhu, Hanjiang; Zou, Ying; Hui, Xiaoying; Maibach, Howard

2017-05-01

This study evaluated the effects of three vehicles-ethanol (EtOH), isopropyl alcohol (IPA), and isopropyl myristate (IPM)-on stratum corneum (SC) absorption and diffusion of the [ 14 C]-model compounds benzoic acid and butenafine hydrochloride to better understand the transport pathways of chemicals passing through and resident in SC. Following application of topical formulations to human dermatomed skin for 30 min, penetration flux was observed for 24 h post dosing, using an in vitro flow-through skin diffusion system. Skin absorption and penetration was compared to the chemical-SC (intact, delipidized, or SC lipid film) binding levels. A significant vehicle effect was observed for chemical skin penetration and SC absorption. IPA resulted in the greatest levels of intact SC/SC lipid absorption, skin penetration, and total skin absorption/penetration of benzoic acid, followed by IPM and EtOH, respectively. For intact SC absorption and total skin absorption/penetration of butenafine, the vehicle that demonstrated the highest level of sorption/penetration was EtOH, followed by IPA and IPM, respectively. The percent doses of butenafine that were absorbed in SC lipid film and penetrated through skin in 24 h were greatest for IPA, followed by EtOH and IPM, respectively. The vehicle effect was consistent between intact SC absorption and total chemical skin absorption and penetration, as well as SC lipid absorption and chemical penetration through skin, suggesting intercellular transport as a main pathway of skin penetration for model chemicals. These results suggest the potential to predict vehicle effects on skin permeability with simple SC absorption assays. As decontamination was applied 30 min after chemical exposure, significant vehicle effects on chemical SC partitioning and percutaneous penetration also suggest that skin decontamination efficiency is vehicle dependent, and an effective decontamination method should act on chemical solutes in the lipid domain.

Katharsis of the skin: Peeling applications and agents of chemical peelings in Greek medical textbooks of Graeco-Roman antiquity.

Science.gov (United States)

Ursin, F; Steger, F; Borelli, C

2018-04-28

Recipes for peelings date back to medical texts of old Egypt. The oldest medical papyri contain recipes for "improving beauty of the skin" and "removing wrinkles" by use of agents like salt and soda. The Egyptian Queen Cleopatra (69-30 BC) is said to have taken bathes in donkey's milk in order to improve the beauty of her skin. However, little is known about other agents and peeling applications in later Greek medical textbooks. We will discover new agents and describe ancient peeling applications. First, we will have to identify ancient Greek medical terms for the modern terms "peeling" and "chemical peeling". Second, based on the identified terms we will perform a systematic fulltext search for agents in original sources. Third, we will categorize the results into three peeling applications: (1) cleansing, (2) aesthetical improvement of the skin, and (3) therapy of dermatological diseases. We performed a full systematic keyword search with the identified Greek terms in databases of ancient Greek texts. Our keywords for peeling and chemical peeling are "smēxis" and "trīpsis". Our keywords for agents of peeling and chemical peeling are "smégmata", "rhýmmata", "kathartiká", and "trímmata". Diocles (4 th century BC) was the first one who mentioned "smēxis" and "trīpsis" as parts of daily cleansing routine. Criton (2 nd century AD) wrote about peeling applications, but any reference to the agents is lost. Antyllos (2 nd century AD) composed three lists of peeling applications including agents. Greek medical textbooks of Graeco-Roman antiquity report several peeling applications like cleansing, brightening, darkening, softening, and aesthetical improvement of the skin by use of peeling and chemical peeling, as well as therapy of dermatological diseases. There are 27 ancient agents for what is contemporarily called peeling and chemical peeling. We discovered more specific agents than hitherto known to research. This article is protected by copyright. All rights

Peptide IC-20, encoded by skin kininogen-1 of the European yellow-bellied toad, Bombina variegata, antagonizes bradykinin-induced arterial smooth muscle relaxation

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Mu Yang

2011-01-01

Full Text Available Objectives: The objectives were to determine if the skin secretion of the European yellow-bellied toad (Bombina variegata, in common with other related species, contains a bradykinin inhibitor peptide and to isolate and structurally characterize this peptide. Materials and Methods: Lyophilized skin secretion obtained from this toad was subjected to reverse phase HPLC fractionation with subsequent bioassay of fractions for antagonism of the bradykinin activity using an isolated rat tail artery smooth muscle preparation. Subsequently, the primary structure of the peptide was established by a combination of microsequencing, mass spectroscopy, and molecular cloning, following which a synthetic replicate was chemically synthesised for bioassay. Results: A single peptide of molecular mass 2300.92 Da was resolved in HPLC fractions of skin secretion and its primary structure determined as IYNAIWP-KH-NK-KPGLL-. Database interrogation with this sequence indicated that this peptide was encoded by skin kininogen-1 previously cloned from B. variegata. The blank cycles were occupied by cysteinyl (C residues and the peptide was located toward the C-terminus of the skin kininogen, and flanked N-terminally by a classical -KR- propeptide convertase processing site. The peptide was named IC-20 in accordance (I = N-terminal isoleucine, C = C-terminal cysteine, 20 = number of residues. Like the natural peptide, its synthetic replicate displayed an antagonism of bradykinin-induced arterial smooth muscle relaxation. Conclusion: IC-20 represents a novel bradykinin antagonizing peptide from amphibian skin secretions and is the third such peptide found to be co-encoded with bradykinins within skin kininogens.

Ultraviolet Radiation Induced Apoptosis in Human Skin In Vivo

Energy Technology Data Exchange (ETDEWEB)

Sheehan, J.M.; Young, A.R

2000-07-01

Sunburn cells, having many characteristics of apoptotic cells, appear in human skin after exposure to UVB. Time-courses and dose responses for solar simulated radiation (SSR)-induced sunburn cells in human volunteers of skin type II have been determined. For the time-course, two groups of volunteers were exposed to two minimal erythema doses (MED) of SSR. Punch biopsies were obtained from Group 1 immediately, 3, 6, 12, 18 and 24 h after SSR exposure and Group 2 were biopsied immediately, 18, 24, 36, 48 and 72 h after exposure. For the dose-response (Group 3), biopsies were taken 24 h after SSR exposure to 0, 0.25, 0.5, 1, 2 and 3 MED. Sections were stained with H and E and also using TUNEL and analysed by light microscopy. Results show a dose-dependent appearance of SBC after SSR exposure. The time point for maximum SBC counts with both H and E staining and TUNEL staining lie between 24 and 36 h. (author)

Ultraviolet Radiation Induced Apoptosis in Human Skin In Vivo

International Nuclear Information System (INIS)

Sheehan, J.M.; Young, A.R.

2000-01-01

Sunburn cells, having many characteristics of apoptotic cells, appear in human skin after exposure to UVB. Time-courses and dose responses for solar simulated radiation (SSR)-induced sunburn cells in human volunteers of skin type II have been determined. For the time-course, two groups of volunteers were exposed to two minimal erythema doses (MED) of SSR. Punch biopsies were obtained from Group 1 immediately, 3, 6, 12, 18 and 24 h after SSR exposure and Group 2 were biopsied immediately, 18, 24, 36, 48 and 72 h after exposure. For the dose-response (Group 3), biopsies were taken 24 h after SSR exposure to 0, 0.25, 0.5, 1, 2 and 3 MED. Sections were stained with H and E and also using TUNEL and analysed by light microscopy. Results show a dose-dependent appearance of SBC after SSR exposure. The time point for maximum SBC counts with both H and E staining and TUNEL staining lie between 24 and 36 h. (author)

Development of an in vitro skin sensitization test based on ROS production in THP-1 cells.

Science.gov (United States)

Saito, Kazutoshi; Miyazawa, Masaaki; Nukada, Yuko; Sakaguchi, Hitoshi; Nishiyama, Naohiro

2013-03-01

Recently, it has been reported that reactive oxygen species (ROS) produced by contact allergens can affect dendritic cell migration and contact hypersensitivity. The aim of the present study was to develop a new in vitro assay that could predict the skin sensitizing potential of chemicals by measuring ROS production in THP-1 (human monocytic leukemia cell line) cells. THP-1 cells were pre-loaded with a ROS sensitive fluorescent dye, 5-(and 6-)-chloromethyl-2', 7'-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA), for 15min, then incubated with test chemicals for 30min. The fluorescence intensity was measured by flow cytometry. For the skin sensitizers, 25 out of 30 induced over a 2-fold ROS production at more than 90% of cell viability. In contrast, increases were only seen in 4 out of 20 non-sensitizers. The overall accuracy for the local lymph node assay (LLNA) was 82% for 50 chemicals tested. A correlation was found between the estimated concentration showing 2-fold ROS production in the ROS assay and the EC3 values (estimated concentration required to induce positive response) of the LLNA. These results indicated that the THP-1 cell-based ROS assay was a rapid and highly sensitive detection system able to predict skin sensitizing potentials and potency of chemicals. Copyright © 2012 Elsevier Ltd. All rights reserved.

Improvement effect of gamma-irradiated complex leaf extract of date plum, persimmon and mulberry on UVB-induced skin damage

Energy Technology Data Exchange (ETDEWEB)

Choi, Ji Won; Cho, Byoung Ok; Che, Denis Nchang; Shin, Jae Young; Fang, Chong Zhou; Jang, Seon Il [Jeonju University, Jeonju (Korea, Republic of)

2016-11-15

This study was conducted to evaluate the improvement effect of gamma-irradiated complex leaf extract of Date Plum, Persimmon and Mulberry (γ-DPME) on UVB induced skin damage. The samples were gamma irradiated at doses of 10 kGy. γ-DPME treatment tended to decrease UVB-induced immune cell infiltration and erthyderma index than the groups treated with non-gamma-irradiated DPME (n-DPME) and L-ascobic acid (AA). In addition, γ-DPME treatment significantly decreased skin thickness, melanin index and mast cell infiltration in UVB-irradiated skin. Moreover, γ-DPME treatment significantly decreased the compound 48/80-induced scratching behavior and immune cell infiltration than n-DPME group. These results show that gamma irradiation can be used to increase the physiological activities of DPME.

Gene expression in skin tumors induced in hairless mice by chronic exposure to ultraviolet B irradiation

International Nuclear Information System (INIS)

Sato, Hiromi; Tanaka, Misao; Kobayashi, Shizuko; Suzuki, Junko S.; Ogiso, Manabu; Tohyama, Chiharu

1997-01-01

We investigated the expressions of c-Ha-ras, c-jun, c-fos, c-myc genes and p53 protein in the development of skin tumours induced by chronic exposure to UVB without a photosensitizer using hairless mice. When mice were exposed to UVB at a dose of 2 kJ/m 2 three times a week, increased c-Ha-ras and c-myc transcripts were detected after only 5 weeks of exposure, while no tumour appeared on the exposed skin. The increase in gene expression continued until 25 weeks, when tumours, identified pathologically as mainly squamous cell carcinomas (SCC), developed in the dorsal skin. In these SCC, overexpression of c-fos mRNA was also observed along with the increases in c-Ha-ras and c-myc. A single dose of UVB (2 kJ/m 2 ) applied to the backs of hairless mice transiently induced overexpression of the early event genes c-fos, c-jun and c-myc, but not c-Ha-ras, in the exposed area of skin. Accumulation of p53 protein was determined by Western blotting analysis of immunohistochemistry using monoclonal antibodies PAb 240 or 246, which recognize mutant or wide type, respectively. In the SCC, a mutant p53 protein accumulated in the cytoplasm and nucleus. After single-dose irradiation, the increased wild-type p53 protein was observed in the nuclei of epidermal cells. The present results suggest that overexpression of the c-fos, c-myc and c-Ha-ras genes, and the mutational changes in p53 protein might be associated with skin photocarcinogenesis. Moreover, overexpression of the c-Ha-ras and c-myc genes might be an early event in the development of UVB-induced skin tumors in mice. (author)

Chemical kinetics of multiphase reactions between ozone and human skin lipids: Implications for indoor air quality and health effects.

Science.gov (United States)

Lakey, P S J; Wisthaler, A; Berkemeier, T; Mikoviny, T; Pöschl, U; Shiraiwa, M

2017-07-01

Ozone reacts with skin lipids such as squalene, generating an array of organic compounds, some of which can act as respiratory or skin irritants. Thus, it is important to quantify and predict the formation of these products under different conditions in indoor environments. We developed the kinetic multilayer model that explicitly resolves mass transport and chemical reactions at the skin and in the gas phase (KM-SUB-Skin). It can reproduce the concentrations of ozone and organic compounds in previous measurements and new experiments. This enabled the spatial and temporal concentration profiles in the skin oil and underlying skin layers to be resolved. Upon exposure to ~30 ppb ozone, the concentrations of squalene ozonolysis products in the gas phase and in the skin reach up to several ppb and on the order of ~10 mmol m -3 . Depending on various factors including the number of people, room size, and air exchange rates, concentrations of ozone can decrease substantially due to reactions with skin lipids. Ozone and dicarbonyls quickly react away in the upper layers of the skin, preventing them from penetrating deeply into the skin and hence reaching the blood. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Wearable, Flexible, and Multifunctional Healthcare Device with an ISFET Chemical Sensor for Simultaneous Sweat pH and Skin Temperature Monitoring.

Science.gov (United States)

Nakata, Shogo; Arie, Takayuki; Akita, Seiji; Takei, Kuniharu

2017-03-24

Real-time daily healthcare monitoring may increase the chances of predicting and diagnosing diseases in their early stages which, currently, occurs most frequently during medical check-ups. Next-generation noninvasive healthcare devices, such as flexible multifunctional sensor sheets designed to be worn on skin, are considered to be highly suitable candidates for continuous real-time health monitoring. For healthcare applications, acquiring data on the chemical state of the body, alongside physical characteristics such as body temperature and activity, are extremely important for predicting and identifying potential health conditions. To record these data, in this study, we developed a wearable, flexible sweat chemical sensor sheet for pH measurement, consisting of an ion-sensitive field-effect transistor (ISFET) integrated with a flexible temperature sensor: we intend to use this device as the foundation of a fully integrated, wearable healthcare patch in the future. After characterizing the performance, mechanical flexibility, and stability of the sensor, real-time measurements of sweat pH and skin temperature are successfully conducted through skin contact. This flexible integrated device has the potential to be developed into a chemical sensor for sweat for applications in healthcare and sports.

Genome-wide transcriptional profiling of skin and dorsal root ganglia after ultraviolet-B-induced inflammation.

Directory of Open Access Journals (Sweden)

John M Dawes

Full Text Available Ultraviolet-B (UVB-induced inflammation produces a dose-dependent mechanical and thermal hyperalgesia in both humans and rats, most likely via inflammatory mediators acting at the site of injury. Previous work has shown that the gene expression of cytokines and chemokines is positively correlated between species and that these factors can contribute to UVB-induced pain. In order to investigate other potential pain mediators in this model we used RNA-seq to perform genome-wide transcriptional profiling in both human and rat skin at the peak of hyperalgesia. In addition we have also measured transcriptional changes in the L4 and L5 DRG of the rat model. Our data show that UVB irradiation produces a large number of transcriptional changes in the skin: 2186 and 3888 genes are significantly dysregulated in human and rat skin, respectively. The most highly up-regulated genes in human skin feature those encoding cytokines (IL6 and IL24, chemokines (CCL3, CCL20, CXCL1, CXCL2, CXCL3 and CXCL5, the prostanoid synthesising enzyme COX-2 and members of the keratin gene family. Overall there was a strong positive and significant correlation in gene expression between the human and rat (R = 0.8022. In contrast to the skin, only 39 genes were significantly dysregulated in the rat L4 and L5 DRGs, the majority of which had small fold change values. Amongst the most up-regulated genes in DRG were REG3B, CCL2 and VGF. Overall, our data shows that numerous genes were up-regulated in UVB irradiated skin at the peak of hyperalgesia in both human and rats. Many of the top up-regulated genes were cytokines and chemokines, highlighting again their potential as pain mediators. However many other genes were also up-regulated and might play a role in UVB-induced hyperalgesia. In addition, the strong gene expression correlation between species re-emphasises the value of the UVB model as translational tool to study inflammatory pain.

Nanodiamonds protect skin from ultraviolet B-induced damage in mice.

Science.gov (United States)

Wu, Meng-Si; Sun, Der-Shan; Lin, Yu-Chung; Cheng, Chia-Liang; Hung, Shih-Che; Chen, Po-Kong; Yang, Jen-Hung; Chang, Hsin-Hou

2015-05-07

Solar ultraviolet (UV) radiation causes various deleterious effects, and UV blockage is recommended for avoiding sunburn. Nanosized titanium dioxide and zinc oxide offer effective protection and enhance cosmetic appearance but entail health concerns regarding their photocatalytic activity, which generates reactive oxygen species. These concerns are absent in nanodiamonds (NDs). Among the UV wavelengths in sunlight, UVB irradiation primarily threatens human health. The efficacy and safety of NDs in UVB protection were evaluated using cell cultures and mouse models. We determined that 2 mg/cm(2) of NDs efficiently reduced over 95% of UVB radiation. Direct UVB exposure caused cell death of cultured keratinocyte, fibroblasts and skin damage in mice. By contrast, ND-shielding significantly protected the aforementioned pathogenic alterations in both cell cultures and mouse models. NDs are feasible and safe materials for preventing UVB-induced skin damage.

Cutaneous exposure to vesicant phosgene oxime: Acute effects on the skin and systemic toxicity

International Nuclear Information System (INIS)

Tewari-Singh, Neera; Goswami, Dinesh G; Kant, Rama; Croutch, Claire R; Casillas, Robert P; Orlicky, David J; Agarwal, Rajesh

2017-01-01

Phosgene Oxime (CX), an urticant or nettle agent categorized as a vesicant, is a potential chemical warfare and terrorist weapon. Its exposure can result in widespread and devastating effects including high mortality due to its fast penetration and ability to cause immediate severe cutaneous injury. It is one of the least studied chemical warfare agents with no effective therapy available. Thus, our goal was to examine the acute effects of CX following its cutaneous exposure in SKH-1 hairless mice to help establish a relevant injury model. Results from our study show that topical cutaneous exposure to CX vapor causes blanching of exposed skin with an erythematous ring, necrosis, edema, mild urticaria and erythema within minutes after exposure out to 8 h post-exposure. These clinical skin manifestations were accompanied with increases in skin thickness, apoptotic cell death, mast cell degranulation, myeloperoxidase activity indicating neutrophil infiltration, p53 phosphorylation and accumulation, and an increase in COX-2 and TNFα levels. Topical CX-exposure also resulted in the dilatation of the peripheral vessels with a robust increase in RBCs in vessels of the liver, spleen, kidney, lungs and heart tissues. These events could cause a drop in blood pressure leading to shock, hypoxia and death. Together, this is the first report on effects of CX cutaneous exposure, which could help design further comprehensive studies evaluating the acute and chronic skin injuries from CX topical exposure and elucidate the related mechanism of action to aid in the identification of therapeutic targets and mitigation of injury. - Highlights: • Phosgene oxime cutaneous exposure causes skin blanching, edema and urticaria. • Penetration of phosgene oxime causes dilation of vasculature in internal organs. • Mast cells could play an important role in phosgene oxime-induced skin injury. • Phosgene oxime could induce low blood pressure and hypoxia leading to mortality. • Data is

Cutaneous exposure to vesicant phosgene oxime: Acute effects on the skin and systemic toxicity

Energy Technology Data Exchange (ETDEWEB)

Tewari-Singh, Neera, E-mail: Neera.tewari-singh@ucdenver.edu [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States); Goswami, Dinesh G; Kant, Rama [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States); Croutch, Claire R; Casillas, Robert P [MRIGlobal, Kansas City, MO 64110 (United States); Orlicky, David J [Department of Pathology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States); Agarwal, Rajesh [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045 (United States)

2017-02-15

Phosgene Oxime (CX), an urticant or nettle agent categorized as a vesicant, is a potential chemical warfare and terrorist weapon. Its exposure can result in widespread and devastating effects including high mortality due to its fast penetration and ability to cause immediate severe cutaneous injury. It is one of the least studied chemical warfare agents with no effective therapy available. Thus, our goal was to examine the acute effects of CX following its cutaneous exposure in SKH-1 hairless mice to help establish a relevant injury model. Results from our study show that topical cutaneous exposure to CX vapor causes blanching of exposed skin with an erythematous ring, necrosis, edema, mild urticaria and erythema within minutes after exposure out to 8 h post-exposure. These clinical skin manifestations were accompanied with increases in skin thickness, apoptotic cell death, mast cell degranulation, myeloperoxidase activity indicating neutrophil infiltration, p53 phosphorylation and accumulation, and an increase in COX-2 and TNFα levels. Topical CX-exposure also resulted in the dilatation of the peripheral vessels with a robust increase in RBCs in vessels of the liver, spleen, kidney, lungs and heart tissues. These events could cause a drop in blood pressure leading to shock, hypoxia and death. Together, this is the first report on effects of CX cutaneous exposure, which could help design further comprehensive studies evaluating the acute and chronic skin injuries from CX topical exposure and elucidate the related mechanism of action to aid in the identification of therapeutic targets and mitigation of injury. - Highlights: • Phosgene oxime cutaneous exposure causes skin blanching, edema and urticaria. • Penetration of phosgene oxime causes dilation of vasculature in internal organs. • Mast cells could play an important role in phosgene oxime-induced skin injury. • Phosgene oxime could induce low blood pressure and hypoxia leading to mortality. • Data is

Modeling skin cooling using optical windows and cryogens during laser induced hyperthermia in a multilayer vascularized tissue

International Nuclear Information System (INIS)

Singh, Rupesh; Das, Koushik; Okajima, Junnosuke; Maruyama, Shigenao; Mishra, Subhash C.

2015-01-01

This article deals with the spatial and the temporal evolution of tissue temperature during skin surface cooled laser induced hyperthermia. Three different skin surface cooling methodologies viz., optical window contact cooling, cryogenic spray cooling and cryogen cooled optical window contact cooling are considered. Sapphire, yttrium aluminum garnet, lithium tantalate, and magnesium oxide doped lithium niobate are the considered optical windows. The cryogens considered are liquid CO_2 and R1234yf. Heat transfer in the multilayer skin tissue embedded with thermally significant blood vessels pairs is modeled using the Pennes and Weinbaum–Jiji bioheat equations. Weinbaum–Jiji bioheat equation is used for the vascularized tissue. Laser transport in the tissue is modeled using the radiative transfer equation. Axial and radial (skin surface) temperature distributions for different combinations of optical windows and cryogens are analyzed. Liquid CO_2 cooled yttrium aluminum garnet is found to be the best surface cooling mechanism. - Highlights: • Skin surface cooled laser induced hyperthermia is studied. • A multi-layer 2-D cylindrical tissue geometry is considered. • Both Pennes and Weinbaum–Jiji bioheat models are considered. • Laser transport in the tissue is modeled using discrete ordinate method. • Results for 4 optical windows and 2 cryogens for skin cooling are presented.

Antioxidant and Anti-Inflammatory Effects of Shungite against Ultraviolet B Irradiation-Induced Skin Damage in Hairless Mice

Directory of Open Access Journals (Sweden)

Ma. Easter Joy Sajo

2017-01-01

Full Text Available As fullerene-based compound applications have been rapidly increasing in the health industry, the need of biomedical research is urgently in demand. While shungite is regarded as a natural source of fullerene, it remains poorly documented. Here, we explored the in vivo effects of shungite against ultraviolet B- (UVB- induced skin damage by investigating the physiological skin parameters, immune-redox profiling, and oxidative stress molecular signaling. Toward this, mice were UVB-irradiated with 0.75 mW/cm2 for two consecutive days. Consecutively, shungite was topically applied on the dorsal side of the mice for 7 days. First, we found significant improvements in the skin parameters of the shungite-treated groups revealed by the reduction in roughness, pigmentation, and wrinkle measurement. Second, the immunokine profiling in mouse serum and skin lysates showed a reduction in the proinflammatory response in the shungite-treated groups. Accordingly, the redox profile of shungite-treated groups showed counterbalance of ROS/RNS and superoxide levels in serum and skin lysates. Last, we have confirmed the involvement of Nrf2- and MAPK-mediated oxidative stress pathways in the antioxidant mechanism of shungite. Collectively, the results clearly show that shungite has an antioxidant and anti-inflammatory action against UVB-induced skin damage in hairless mice.

Intervention of radiation‐induced skin fibrosis by RNA interference

DEFF Research Database (Denmark)

Nawroth, Isabel

‐α (TNFα) production by macrophages might promote RIF. RNA interference (RNAi) is an evolutionary conserved gene‐silencing mechanism capable of degrading mRNA containing a homologous sequence to an exogenously introduced double stranded small interfering RNA (siRNA). These siRNAs can induce RNAi...... and inhibit the expression of target proteins. Therefore, siRNAs are considered as promising therapeutics for treatment of various diseases including genetic and viral diseases, and cancer. In this study, the therapeutic potential of RNA interference was investigated as an intervention strategy for radiation......‐induced skin fibrosis. Chitosan‐based nanoparticles (or polyplexes) formed by self‐assembly with siRNA were applied to overcome extracellular and intracellular barriers and deliver siRNA site‐specific. In this work we show that intraperitoneal administration of chitosan/DsiRNA nanoparticles targeting TNFα...

Evidence and Considerations in the Application of Chemical Peels in Skin Disorders and Aesthetic Resurfacing

Science.gov (United States)

Berson, Diane S.; Cohen, Joel L.; Roberts, Wendy E.; Starker, Isaac; Wang, Beatrice

2010-01-01

Chemical peeling is a popular, relatively inexpensive, and generally safe method for treatment of some skin disorders and to refresh and rejuvenate skin. This article focuses on chemical peels and their use in routine clinical practice. Chemical peels are classified by the depth of action into superficial, medium, and deep peels. The depth of the peel is correlated with clinical changes, with the greatest change achieved by deep peels. However, the depth is also associated with longer healing times and the potential for complications. A wide variety of peels are available, utilizing various topical agents and concentrations, including a recent salicylic acid derivative, β-lipohydroxy acid, which has properties that may expand the clinical use of peels. Superficial peels, penetrating only the epidermis, can be used to enhance treatment for a variety of conditions, including acne, melasma, dyschromias, photodamage, and actinic keratoses. Medium-depth peels, penetrating to the papillary dermis, may be used for dyschromia, multiple solar keratoses, superficial scars, and pigmentary disorders. Deep peels, affecting reticular dermis, may be used for severe photoaging, deep wrinkles, or scars. Peels can be combined with other in-office facial resurfacing techniques to optimize outcomes and enhance patient satisfaction and allow clinicians to tailor the treatment to individual patient needs. Successful outcomes are based on a careful patient selection as well as appropriate use of specific peeling agents. Used properly, the chemical peel has the potential to fill an important therapeutic need in the dermatologist's and plastic surgeon's armamentarium. PMID:20725555

Inhibitory effect of cucurbitacin B on imiquimod-induced skin inflammation

Energy Technology Data Exchange (ETDEWEB)

Li, Zheng Jun; Shin, Jung-Min; Choi, Dae-Kyoung; Lim, Seul Ki [Department of Dermatology, School of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Yoon, Tae-Jin [Department of Dermatology, School of Medicine, Gyeongsang National University, Jinju (Korea, Republic of); Lee, Young Ho [Department of Anatomy, School of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Sohn, Kyung-Cheol; Im, Myung; Lee, Young; Seo, Young-Joon; Kim, Chang Deok [Department of Dermatology, School of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Lee, Jeung-Hoon, E-mail: jhoon@cnu.ac.kr [Department of Dermatology, School of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Skin Med Company, Daejeon (Korea, Republic of)

2015-04-17

Psoriasis is a common skin disease, of which pathogenesis involves the increase of inflammatory reaction in epidermal cells. In an attempt to find therapeutics for psoriasis, we found that cucurbitacin B has an inhibitory potential on imiquimod-induced inflammation of keratinocytes. Cucurbitacin B significantly inhibited imiquimod-induced expression of crucial psoriatic cytokines, such as IL-8 and CCL20, via down-regulation of NF-κB and STAT3 signaling pathway in human keratinocytes. In addition, keratinocyte proliferation was markedly inhibited by cucurbitacin B. The potential beneficial effect of cucurbitacin B on psoriasis was further validated in imiquimod-induced psoriasiform dermatitis of experimental animal. Topical application of cucurbitacin B resulted in significant reduction of epidermal hyperplasia and inflammatory cytokines production, and ameliorated the psoriatic symptom. Taken together, these results suggest that cucurbitacin B may be a potential candidate for the treatment of psoriasis. - Highlights: • Cucurbitacin B has a potential for inhibiting the growth of keratinocytes. • Cucurbitacin B inhibits imiquimod-induced inflammatory reaction in keratinocytes. • Cucurbitacin B inhibits imiquimod-induced psoriasiform dermatitis in experimental animal.

Inhibitory effect of cucurbitacin B on imiquimod-induced skin inflammation

International Nuclear Information System (INIS)

Li, Zheng Jun; Shin, Jung-Min; Choi, Dae-Kyoung; Lim, Seul Ki; Yoon, Tae-Jin; Lee, Young Ho; Sohn, Kyung-Cheol; Im, Myung; Lee, Young; Seo, Young-Joon; Kim, Chang Deok; Lee, Jeung-Hoon

2015-01-01

Psoriasis is a common skin disease, of which pathogenesis involves the increase of inflammatory reaction in epidermal cells. In an attempt to find therapeutics for psoriasis, we found that cucurbitacin B has an inhibitory potential on imiquimod-induced inflammation of keratinocytes. Cucurbitacin B significantly inhibited imiquimod-induced expression of crucial psoriatic cytokines, such as IL-8 and CCL20, via down-regulation of NF-κB and STAT3 signaling pathway in human keratinocytes. In addition, keratinocyte proliferation was markedly inhibited by cucurbitacin B. The potential beneficial effect of cucurbitacin B on psoriasis was further validated in imiquimod-induced psoriasiform dermatitis of experimental animal. Topical application of cucurbitacin B resulted in significant reduction of epidermal hyperplasia and inflammatory cytokines production, and ameliorated the psoriatic symptom. Taken together, these results suggest that cucurbitacin B may be a potential candidate for the treatment of psoriasis. - Highlights: • Cucurbitacin B has a potential for inhibiting the growth of keratinocytes. • Cucurbitacin B inhibits imiquimod-induced inflammatory reaction in keratinocytes. • Cucurbitacin B inhibits imiquimod-induced psoriasiform dermatitis in experimental animal

Biological Mechanisms Underlying the Ultraviolet Radiation-Induced Formation of Skin Wrinkling and Sagging I: Reduced Skin Elasticity, Highly Associated with Enhanced Dermal Elastase Activity, Triggers Wrinkling and Sagging

Science.gov (United States)

Imokawa, Genji; Ishida, Koichi

2015-01-01

The repetitive exposure of skin to ultraviolet B (UVB) preferentially elicits wrinkling while ultraviolet A (UVA) predominantly elicits sagging. In chronically UVB or UVA-exposed rat skin there is a similar tortuous deformation of elastic fibers together with decreased skin elasticity, whose magnitudes are greater in UVB-exposed skin than in UVA-exposed skin. Comparison of skin elasticity with the activity of matrix metalloproteinases (MMPs) in the dermis of ovariectomized rats after UVB or UVA irradiation demonstrates that skin elasticity is more significantly decreased in ovariectomized rats than in sham-operated rats, which is accompanied by a reciprocal increase in elastase activity but not in the activities of collagenases I or IV. Clinical studies using animal skin and human facial skin demonstrated that topical treatment with a specific inhibitor or an inhibitory extract of skin fibroblast-derived elastase distinctly attenuates UVB and sunlight-induced formation of wrinkling. Our results strongly indicated that the upregulated activity of skin fibroblast-derived elastase plays a pivotal role in wrinkling and/or sagging of the skin via the impairment of elastic fiber configuration and the subsequent loss of skin elasticity. PMID:25856675

Nitric oxide-releasing sulindac is a novel skin cancer chemopreventive agent for UVB-induced photocarcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Chaudhary, Sandeep C.; Singh, Tripti; Kapur, Puneet; Weng, Zhiping; Arumugam, Aadithya; Elmets, Craig A. [Department of Dermatology, University of Alabama at Birmingham, 1530 3rd Avenue South, VH509, Birmingham, AL 35294-0019 (United States); Kopelovich, Levy [Division of Cancer Prevention, National Cancer Institute, 6130 Executive Blvd, Suite 2114, Bethesda, MD 20892 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology, University of Alabama at Birmingham, 1530 3rd Avenue South, VH509, Birmingham, AL 35294-0019 (United States)

2013-05-01

Nitric oxide (NO)-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) which have been synthesized to reduce gastro-intestinal and cardiovascular toxicities of NSAIDs, possess anti-proliferative, pro-apoptotic and anti-cancer activities. Here, we show that NO-sulindac inhibited UVB-induced skin tumorigenesis in SKH-1 hairless mice. Topical application of NO-sulindac reduced tumor incidence, number (p < 0.05) and volume (p < 0.005) as compared to UVB (alone)-irradiated vehicle-treated mice. An increase in TUNEL-positive cells in skin lesions was accompanied by the enhanced Bax:Bcl-2 ratio. The expression of pro-apoptotic Bax was increased whereas anti-apoptotic Bcl-2 reduced. However, proliferation was identified as the major target of NO-sulindac in this study. A reduced expression of PCNA and cyclin D1 associated with the dampening of cell cycle progression was observed. The mechanism of this inhibition was related to the reduction in UVB-induced Notch signaling pathway. UVB-induced inflammatory responses were diminished by NO-sulindac as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases Erk1/2, p38 and JNK1/2. In this regard, NO-sulindac also inhibited NFκB by enhancing IκBα as evidenced by the reduced expression of iNOS and COX-2, the direct NFκB transcription target proteins. NO-sulindac significantly diminished the progression of benign lesions to invasive carcinomas by suppressing the tumor aggressiveness and retarding epithelial–mesenchymal transition. A marked decrease in the expression of mesenchymal markers such as Fibronectin, N-cadherin, SNAI, Slug and Twist and an increase in epithelial cell polarity marker E-cadherin were noted in NO-sulindac-treated tumors. Our data suggest that NO-sulindac is a potent inhibitor of UVB-induced skin carcinogenesis and acts by targeting proliferation-regulatory pathways. - Highlights: ► NO-sulindac is a potent chemopreventive agent for UVB-induced skin cancer. ► NO

Measuring the arterial-induced skin vibration by geometrical moiré fringe

Science.gov (United States)

Chiu, Shih-Yung; Wang, Chun-Hsiung; Lee, Shu-Sheng; Wu, Wen-Jong; Hsu, Yu-Hsiang; Lee, Chih-Kung

2018-02-01

The demand for self-measured blood pressure self-monitoring device has much increased due to cardiovascular diseases have become leading causes of death for aging population. Currently, the primary non-invasive blood pressure monitoring method is cuff-based. It is well developed and accurate. However, the measuring process is not comfortable, and it cannot provide a continuous measurement. To overcome this problem, methods such as tonometry, volume clamp method, photoplethysmography, pulse wave velocity, and pulse transit time are reported. However, the limited accuracy hindered its application for diagnostics. To perform sequential blood pressure measurement with a high accuracy and long-term examination, we apply moiré interferometry to measure wrist skin vibration induced by radial artery. To achieve this goal, we developed a miniaturized device that can perform moiré interferometry around the wrist region. The 0.4-mm-pitched binary grating and tattoo sticker with 0.46 mm-pitched stripe pattern are used to perform geometric moiré. We demonstrated that the sensitivity and accuracy of this integrated system were sufficient to monitor arterialinduced skin vibration non-invasively. Our developed system was validated with ECG signals collected by a commercial system. According to our studies from measurement, the repeatability of wrist pulsation measurement was achieved with an accuracy of 99.1% in heart rate. A good repeatability of wrist pulse measurement was achieved. Simulations and experiments are both conducted in this paper and prove of geometrical moiré method a suitable technique for arterial-induced skin vibration monitoring.

Chemical Peels

Science.gov (United States)

... for Every Season How to Choose the Best Skin Care Products In This Section Dermatologic Surgery What is dermatologic ... for Every Season How to Choose the Best Skin Care Products Chemical Peels Uses for Chemical Peels Learn more ...

Suitability of macrophage inflammatory protein-1beta production by THP-1 cells in differentiating skin sensitizers from irritant chemicals.

Science.gov (United States)

Lim, Yeon-Mi; Moon, Seong-Joon; An, Su-Sun; Lee, Soo-Jin; Kim, Seo-Young; Chang, Ih-Seop; Park, Kui-Lea; Kim, Hyoung-Ah; Heo, Yong

2008-04-01

Worldwide restrictions in animal use for research have driven efforts to develop alternative methods. The study aimed to test the efficacy of the macrophage inflammatory protein-1beta (MIP-1beta) assay for testing chemicals' skin-sensitizing capacity. The assay was performed using 9 chemicals judged to be sensitizing and 7 non-sensitizing by the standard in vivo assays. THP-1 cells were cultured in the presence or absence of 4 doses, 0.01x, 0.1x, 0.5x, or 1x IC(50) (50% inhibitory concentration for THP-1 cell proliferation) of these chemicals for 24 hr, and the MIP-1beta level in the supernatants was determined. Skin sensitization by the test chemicals was determined by MIP-1beta production rates. The MIP-1beta production rate was expressed as the relative increase in MIP-1beta production in response to chemical treatment compared with vehicle treatment. When the threshold MIP-1beta production rate used was 100% or 105% of dimethyl sulfoxide, all the sensitizing chemicals tested (dinitrochlorobenzene, hexyl cinnamic aldehyde, eugenol, hydroquinone, dinitrofluorobenzene, benzocaine, nickel, chromium, and 5-chloro-2-methyl-4-isothiazolin-3-one) were positive, and all the non-sensitizing chemicals (methyl salicylate, benzalkonium chloride, lactic acid, isopropanol, and salicylic acid), with the exception of sodium lauryl sulfate, were negative for MIP-1beta production. These results indicate that MIP-1beta could be a biomarker for classification of chemicals as sensitizers or non-sensitizers.

Hataedock treatment has preventive therapeutic effects for atopic dermatitis through skin barrier protection in Dermatophagoides farinae-induced NC/Nga mice.

Science.gov (United States)

Cha, Ho-Yeol; Ahn, Sang-Hyun; Cheon, Jin-Hong; Park, Sun-Young; Kim, Kibong

2017-07-12

Hataedock treatment is traditionally used for the purpose of preventing the future skin disease by feeding herbal extracts to the newborn in traditional Chinese and Korean medicine. This study investigated the preventive therapeutic effects of Hataedock (HTD) treatment for atopic dermatitis (AD) through skin barrier protection in Dermatophagoides farinae-induced NC/Nga mice. To the HTD treatment group, the extract of Coptis japonica Makino and Glycyrrhiza uralensis Fischer, which analyzed with High Performance Liquid Chromatography (HPLC)-fingerprint for quality consistency, was administered orally to the 3-week-old mice before inducing AD. After that, Dermatophagoides farinae was applied except the control group to induce AD-like skin lesions. We confirmed the effects of HTD on morphological changes, protection of skin barrier, regulation of Th2 differentiation, inflammation regulation and induction of apoptosis through histochemistry, immunohistochemistry, and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. HTD effectively reduced edema, angiogenesis and skin lesion. HTD also increased the levels of liver X receptor (LXR) and filaggrin but decreased the level of protein kinase C (PKC) (pprotection of skin barrier. Therefore, HTD may have potential applications for alternative and preventive treatment in the management of AD. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Nicotinamide enhances repair of arsenic and ultraviolet radiation-induced DNA damage in HaCaT keratinocytes and ex vivo human skin.

Directory of Open Access Journals (Sweden)

Benjamin C Thompson

Full Text Available Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen with ultraviolet (UV radiation and affects DNA damage and repair. Nicotinamide (vitamin B3 reduces premalignant keratoses in sun-damaged skin, likely by prevention of UV-induced cellular energy depletion and enhancement of DNA repair. We investigated whether nicotinamide modifies DNA repair following exposure to UV radiation and sodium arsenite. HaCaT keratinocytes and ex vivo human skin were exposed to 2μM sodium arsenite and low dose (2J/cm2 solar-simulated UV, with and without nicotinamide supplementation. DNA photolesions in the form of 8-oxo-7,8-dihydro-2'-deoxyguanosine and cyclobutane pyrimidine dimers were detected by immunofluorescence. Arsenic exposure significantly increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine in irradiated cells. Nicotinamide reduced both types of photolesions in HaCaT keratinocytes and in ex vivo human skin, likely by enhancing DNA repair. These results demonstrate a reduction of two different photolesions over time in two different models in UV and arsenic exposed cells. Nicotinamide is a nontoxic, inexpensive agent with potential for chemoprevention of arsenic induced skin cancer.

Chemical-induced allergy and autoimmunity

NARCIS (Netherlands)

Wulferink, Marty Bernardus Franciscus

2001-01-01

This thesis aims towards a better understanding of the mechanisms that lead to chemical-induced adverse immune effects. We focussed thereby on the initial induction stage of the immune reaction that consists of three major steps: (i) formation of neoantigen, (ii) processing and presentation of the

A case of likely radiation-induced synchronous esophageal and skin carcinoma following post-operative radiation for breast cancer

International Nuclear Information System (INIS)

Kanogawa, Naoya; Shimada, Hideaki; Kainuma, Osamu; Cho, Akihiro; Yamamoto, Hiroshi; Itami, Makiko; Nagata, Matsuo

2009-01-01

A 71-year-old woman was admitted in January 2008 with on upper thoracic esophageal squamous cell carcinoma and a right chest wall skin tumor. When she was 32 years old, she had a radical mastectomy for right breast cancer and received postoperative radiation. Due to the presence of lung adhesions, trans-thoracic esophagectomy could not be done; thus, a blunt dissection was performed. She was discharged on the 19 th postoperative day. On pathology, a pT2N0M0 (pStage II) esophageal tumor was diagnosed. A resection of her skin tumor underwent 79 days after the esophageal surgery; on pathology, the skin tumor was diagnosed as a basal cell carcinoma. Since the esophageal tumor and the skin tumor occurred in the same area that had received radiation therapy, these tumors were diagnosed as being radiation-induced secondary tumors. In the English language medical literature, several reports of radiation-induced esophageal cancer occurring as a second cancer after radiotherapy for breast cancer have been published. Radiation-induced esophageal cancer rates may increase in Japan given the number of women who previously received radiotherapy for breast cancer. (author)

Performance of a novel keratinocyte-based reporter cell line to screen skin sensitizers in vitro

International Nuclear Information System (INIS)

Emter, Roger; Ellis, Graham; Natsch, Andreas

2010-01-01

In vitro tests are needed to replace animal tests to screen for the skin sensitization potential of chemicals. Skin sensitizers are electrophilic molecules and the Nrf2-electrophile-sensing pathway comprising the repressor protein Keap1, the transcription factor Nrf2 and the antioxidant response element (ARE) is emerging as a toxicity pathway induced by skin sensitizers. Previously, we screened a large set of chemicals in the reporter cell line AREc32, which contains an eight-fold repeat of the rat GSTA2 ARE-sequence upstream of a luciferase reporter gene in the human breast cancer cell line MCF7. This approach was now further developed to bring it closer to the conditions in the human skin and to propose a fully standardized assay. To this end, a luciferase reporter gene under control of a single copy of the ARE-element of the human AKR1C2 gene was stably inserted into HaCaT keratinocytes. A standard operating procedure was developed whereby chemicals are routinely tested at 12 concentrations in triplicate for significant induction of gene activity. We report results from this novel assay on (i) a list of reference chemicals published by ECVAM, (ii) the ICCVAM list of chemicals for validation of alternative endpoints in the LLNA and (iii) on a more general list of 67 chemicals derived from the ICCVAM database. For comparison, peptide reactivity data are presented for the same chemicals. The results indicate a good predictive value of this approach for hazard identification. Its technical simplicity, the high-throughput format and the good predictivity may make this assay a candidate for rapid validation to meet the tight deadline to replace animal tests for skin sensitization by 2013 set by the European authorities.

The local lymph node assay and skin sensitization testing.

Science.gov (United States)

Kimber, Ian; Dearman, Rebecca J

2010-01-01

The mouse local lymph node assay (LLNA) is a method for the identification and characterization of skin sensitization hazards. In this context the method can be used both to identify contact allergens, and also determine the relative skin sensitizing potency as a basis for derivation of effective risk assessments.The assay is based on measurement of proliferative responses by draining lymph node cells induced following topical exposure of mice to test chemicals. Such responses are known to be causally and quantitatively associated with the acquisition of skin sensitization and therefore provide a relevant marker for characterization of contact allergic potential.The LLNA has been the subject of exhaustive evaluation and validation exercises and has been assigned Organization for Economic Cooperation and Development (OECD) test guideline 429. Herein we describe the conduct and interpretation of the LLNA.

Prospective evaluation of radiation-induced skin toxicity in a race/ethnically diverse breast cancer population

International Nuclear Information System (INIS)

Wright, Jean L.; Takita, Cristiane; Reis, Isildinha M.; Zhao, Wei; Lee, Eunkyung; Nelson, Omar L.; Hu, Jennifer J.

2016-01-01

We evaluated predictors of radiation-induced skin toxicity in a prospective study of a tri-racial/ethnic breast cancer population. We evaluated patient demographics, tumor characteristics, and treatment variables in the first 392 patients in a prospective study assessing radiation-induced skin toxicity. Logistic regression analyses were conducted to evaluate potential predictors of skin toxicity. The study consists of 59 non-Hispanic whites (NHW; 15%), 241 Hispanic Whites (HW; 62%), 79 black or African Americans (AA; 20%), and 13 others (3%). Overall, 48% developed grade 0–1 skin toxicity, 49.8% grade 2, and 2.2% grade 3 by the National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE) scale. Twenty-one percent developed moist desquamation. In multivariate analysis, higher body mass index (BMI; OR = 2.09; 95%CI = 1.15, 3.82), higher disease stage (OR = 1.82; 95%CI = 1.06, 3.11), ER-positive/PR-negative status (OR = 2.74; 95%CI = 1.26, 5.98), and conventionally fractionated regimens (OR = 3.25; 95%CI = 1.76, 6.01) were significantly associated with higher skin toxicity grade after adjustment for age, race, ethnicity, ER status, and breast volume. BMI specifically predicted for moist desquamation, but not degree of erythema. In this racially and ethnically diverse cohort of breast cancer patients receiving radiation to the intact breast, risk factors including BMI, disease stage, and conventionally fractionated radiation predicted for higher skin toxicity grade, whereas age, race, ethnicity, and breast volume did not. BMI specifically predicted for moist desquamation, suggesting that preventive measures to address this particular outcome should be investigated

Environment and the skin

International Nuclear Information System (INIS)

Suskind, R.R.

1990-01-01

The skin is an important organ of defense adaptation and a portal of entry for xenobiotics. It is vulnerable to physical, chemical, and biologic agents and capable of expressing responses to these agents in a variety of pathologic patterns. These patterns are characterized by morphologic and functional features which are elicited by careful examination and test procedures. Cutaneous cancer may result from exposure to nonionizing as well as ionizing radiation, to specific identifiable chemical hazards, and may be enhanced by trauma. Cutaneous hazards of chemical sources are largely found in the workplace and among consumer products, including drugs and toilet goods. Environmental skin diseases and injuries are preventable. Prior to use assessment for safety and for possible risks from exposure to an agent, product, or process is of primary importance in the prevention and control of environmental skin disease and injury

UVA-induced mutational spectra in the laci gene from transgenic mouse skin

International Nuclear Information System (INIS)

Gorelick, N.J.; O'Kelly, J.A.; Biedermann, K.A.

1995-01-01

The UVB (295-320 nm) component of sunlight was once thought to be the sole cause of photoaging and skin cancer. However, there is now compelling evidence to suggest that chronic irradiation with UVA (320-400 nm) is a significant component of the etiologies of these diseases. To identify acute markers of UVA damage, we investigated UVA-induced mutagenesis in vivo by using a lacI transgenic mouse mutation assay. The backs of adult female C57BL/6 Big Blue reg-sign mice were shaved and exposed daily to a low or a high dose of UVA for 5 consecutive days. One group remained unexposed. The high dose of UVA significantly increased the mutant frequency in skin determined 12 days after the last exposure. Mutant frequencies were (Avg ± SEM, n=7-8/group): 6.1 ± 0.5 x 10 -5 (high dose). DNA sequence analysis of mutant lacI genes demonstrated that the high dose of UVA produced a different mutational spectrum compared to control. The mutational spectrum from the low dose mutants was not different from the control spectrum in skin generated previously; the predominant classes of recovered mutations were GC→At transitions at CpG sites (11/35) and GC →TA transversions (12/35). In contrast, in the high dose group, GC →AT transitions at non-CpG sites predominated (61/97 mutations); three tandem base substitutions (1 GG →AA; 2 CC→TT) were uniquely recovered; and an increased frequency of recovered GC→CG substitutions was observed (12/97 vs. none in controls). The recovered high dose spectrum is consistent with the types of DNA damage generated by UVA as well as by reactive oxygen species. These studies demonstrate that UVA is mutagenic in vivo and that this assay can be used to study early events in UVA-induced skin damage

Antioxidant, immunomodulatory and antiproliferative effects of gelatin hydrolysate from unicorn leatherjacket skin.

Science.gov (United States)

Karnjanapratum, Supatra; O'Callaghan, Yvonne C; Benjakul, Soottawat; O'Brien, Nora

2016-07-01

The in vitro cellular bioactivities including, antioxidant, immunomodulatory and antiproliferative effects of a gelatin hydrolysate (GH) prepared from unicorn leatherjacket skin, using partially purified glycyl endopeptidase, were investigated in order to optimize the use of fish skin waste products as functional food ingredients. GH under the tested concentrations (750-1500 µg mL(-1) ) protected against H2 O2 -induced DNA damage in U937 cells. GH also protected against the H2 O2 -induced reduction in cellular antioxidant enzyme activities, superoxide dismutase and catalase, in HepG2 cells. GH demonstrated immunomodulatory potential by reducing pro-inflammatory cytokine (interleukin-6 (IL-6) and IL-1β) production and nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Cell proliferation in human colon cancer (Caco-2) cells was significantly reduced in a dose-dependent manner following incubation with GH. These results indicate that GH has several bioactivities which support its potential as a promising functional food ingredient with various health benefits. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Flavonols Protect Against UV Radiation-Induced Thymine Dimer Formation in an Artificial Skin Mimic.

Science.gov (United States)

Maini, Sabia; Fahlman, Brian M; Krol, Ed S

2015-01-01

Exposure of skin to ultraviolet light has been shown to have a number of deleterious effects including photoaging, photoimmunosuppression and photoinduced DNA damage which can lead to the development of skin cancer. In this paper we present a study on the ability of three flavonols to protect EpiDerm™, an artificial skin mimic, against UV-induced damage. EpiDerm™ samples were treated with flavonol in acetone and exposed to UVA (100 kJ/m(2) at 365 nm) and UVB (9000 J/m(2) at 310 nm) radiation. Secretion of matrix metalloproteinase-1 (MMP-1) and tumor necrosis factor-α (TNF-a) were determined by ELISA, cyclobutane pyrimidine dimers were quantified using LC-APCI-MS. EpiDerm™ treated topically with quercetin significantly decreased MMP-1 secretion induced by UVA (100 µM) or UVB (200 µM) and TNF-a secretion was significantly reduced at 100 µM quercetin for both UVA and UVB radiation. In addition, topically applied quercetin was found to be photostable over the duration of the experiment. EpiDerm™ samples were treated topically with quercetin, kaempferol or galangin (52 µM) immediately prior to UVA or UVB exposure, and the cyclobutane thymine dimers (T-T (CPD)) were quantified using an HPLC-APCI MS/MS method. All three flavonols significantly decreased T-T (CPD) formation in UVB irradiated EpiDerm™, however no effect could be observed for the UVA irradiation experiments as thymine dimer formation was below the limit of quantitation. Our results suggest that flavonols can provide protection against UV radiation-induced skin damage through both antioxidant activity and direct photo-absorption. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

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

Science.gov (United States)

Sumiyoshi, Maho; Kimura, Yoshiyuki

2009-12-01

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

Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins.

Science.gov (United States)

Zenz, Rainer; Eferl, Robert; Kenner, Lukas; Florin, Lore; Hummerich, Lars; Mehic, Denis; Scheuch, Harald; Angel, Peter; Tschachler, Erwin; Wagner, Erwin F

2005-09-15

Psoriasis is a frequent, inflammatory disease of skin and joints with considerable morbidity. Here we report that in psoriatic lesions, epidermal keratinocytes have decreased expression of JunB, a gene localized in the psoriasis susceptibility region PSORS6. Likewise, inducible epidermal deletion of JunB and its functional companion c-Jun in adult mice leads (within two weeks) to a phenotype resembling the histological and molecular hallmarks of psoriasis, including arthritic lesions. In contrast to the skin phenotype, the development of arthritic lesions requires T and B cells and signalling through tumour necrosis factor receptor 1 (TNFR1). Prior to the disease onset, two chemotactic proteins (S100A8 and S100A9) previously mapped to the psoriasis susceptibility region PSORS4, are strongly induced in mutant keratinocytes in vivo and in vitro. We propose that the abrogation of JunB/activator protein 1 (AP-1) in keratinocytes triggers chemokine/cytokine expression, which recruits neutrophils and macrophages to the epidermis thereby contributing to the phenotypic changes observed in psoriasis. Thus, these data support the hypothesis that epidermal alterations are sufficient to initiate both skin lesions and arthritis in psoriasis.

Surface chemical reactions induced by molecules electronically-excited in the gas

DEFF Research Database (Denmark)

Petrunin, Victor V.

2011-01-01

and alignment are taking place, guiding all the molecules towards the intersections with the ground state PES, where transitions to the ground state PES will occur with minimum energy dissipation. The accumulated kinetic energy may be used to overcome the chemical reaction barrier. While recombination chemical...... be readily produced. Products of chemical adsorption and/or chemical reactions induced within adsorbates are aggregated on the surface and observed by light scattering. We will demonstrate how pressure and spectral dependencies of the chemical outcomes, polarization of the light and interference of two laser...... beams inducing the reaction can be used to distinguish the new process we try to investigate from chemical reactions induced by photoexcitation within adsorbed molecules and/or gas phase photolysis....

Biologic activities of molecular chaperones and pharmacologic chaperone imidazole-containing dipeptide-based compounds: natural skin care help and the ultimate challenge: implication for adaptive responses in the skin.

Science.gov (United States)

Babizhayev, Mark A; Nikolayev, Gennady M; Nikolayeva, Juliana G; Yegorov, Yegor E

2012-03-01

Accumulation of molecular damage and increased molecular heterogeneity are hallmarks of photoaged skin and pathogenesis of human cutaneous disease. Growing evidence demonstrates the ability of molecular chaperone proteins and of pharmacologic chaperones to decrease the environmental stress and ameliorate the oxidation stress-related and glycation disease phenotypes, suggesting that the field of chaperone therapy might hold novel treatments for skin diseases and aging. In this review, we examine the evidence suggesting a role for molecular chaperone proteins in the skin and their inducer and protecting agents: pharmacologic chaperone imidazole dipeptide-based agents (carcinine and related compounds) in cosmetics and dermatology. Furthermore, we discuss the use of chaperone therapy for the treatment of skin photoaging diseases and other skin pathologies that have a component of increased glycation and/or free radical-induced oxidation in their genesis. We examine biologic activities of molecular and pharmacologic chaperones, including strategies for identifying potential chaperone compounds and for experimentally demonstrating chaperone activity in in vitro and in vivo models of human skin disease. This allows the protein to function and traffic to the appropriate location in the skin, thereby increasing protein activity and cellular function and reducing stress on skin cells. The benefits of imidazole dipeptide antioxidants with transglycating activity (such as carcinine) in skin care are that they help protect and repair cell membrane damage and help retain youthful, younger-looking skin. All skin types will benefit from daily, topical application of pharmacologic chaperone antioxidants, anti-irritants, in combination with water-binding protein agents that work to mimic the structure and function of healthy skin. General strategies are presented addressing ground techniques to improve absorption of usually active chaperone proteins and dipeptide compounds, include

Ultrasound-induced cavitation damage to external epithelia of fish skin.

Science.gov (United States)

Frenkel, V; Kimmel, E; Iger, Y

1999-10-01

Transmission electron microscopy was used to show the effects of therapeutic ultrasound (fish skin. Exposures of up to 90 s produced damage to 5 to 6 of the outermost layers. Negligible temperature elevations and lack of damage observed when using degassed water indicated that the effects were due to cavitation. The minimal intensity was determined for inducing cellular damage, where the extent and depth of damage to the tissues was correlated to the exposure duration. The results may be interpreted as a damage front, advancing slowly from the outer cells inward, presumably in association with the slow replacement of the perforated cell contents with the surrounding water. This study illustrates that a controlled level of microdamage may be induced to the outer layers of the tissues.

Utilization of reconstructed cultured human skin models as an alternative skin for permeation studies of chemical compounds

OpenAIRE

Kano, Satoshi; 藤堂, 浩明; 杉江, 謙一; 藤本, 英哲; 中田, 圭一; 徳留, 嘉寛; 橋本, フミ惠; 杉林, 堅次

2010-01-01

Two reconstructed human skin models, EpiskinSM and EpiDermTM, have been approved as alternative membranes for skin corrosive/irritation experiments due to their close correlation with animal skin. Such reconstructed human skin models were evaluated as alternative membranes for skin permeation experiments. Seven drugs with different lipophilicities and almost the same molecular weight were used as test penetrants. Relationships were investigated between permeability coefficients (P values) of ...

FEM modeling and histological analyses on thermal damage induced in facial skin resurfacing procedure with different CO2 laser pulse duration

Science.gov (United States)

Rossi, Francesca; Zingoni, Tiziano; Di Cicco, Emiliano; Manetti, Leonardo; Pini, Roberto; Fortuna, Damiano

2011-07-01

Laser light is nowadays routinely used in the aesthetic treatments of facial skin, such as in laser rejuvenation, scar removal etc. The induced thermal damage may be varied by setting different laser parameters, in order to obtain a particular aesthetic result. In this work, it is proposed a theoretical study on the induced thermal damage in the deep tissue, by considering different laser pulse duration. The study is based on the Finite Element Method (FEM): a bidimensional model of the facial skin is depicted in axial symmetry, considering the different skin structures and their different optical and thermal parameters; the conversion of laser light into thermal energy is modeled by the bio-heat equation. The light source is a CO2 laser, with different pulse durations. The model enabled to study the thermal damage induced into the skin, by calculating the Arrhenius integral. The post-processing results enabled to study in space and time the temperature dynamics induced in the facial skin, to study the eventual cumulative effects of subsequent laser pulses and to optimize the procedure for applications in dermatological surgery. The calculated data where then validated in an experimental measurement session, performed in a sheep animal model. Histological analyses were performed on the treated tissues, evidencing the spatial distribution and the entity of the thermal damage in the collageneous tissue. Modeling and experimental results were in good agreement, and they were used to design a new optimized laser based skin resurfacing procedure.

Alpha-hydroxyacid chemical peeling agents: case studies and rationale for safe and effective use.

Science.gov (United States)

Briden, M Elizabeth

2004-02-01

Chemical peeling is an in-office procedure that involves the application of a chemical agent to the skin to induce controlled destruction or exfoliation of old skin and stimulation of new epidermal growth with more evenly distributed melanin. When peel agents reach the dermal layer, important wound-healing activities occur that cause skin remodeling and skin smoothing, both antiaging benefits. There are a number of key factors in selecting a peeling agent and procedure, and each is discussed. Variables to consider are the peeling agent and its formulation, the concentration of the agent, the patient's skin type, the site to be peeled, the skin preparation procedure prior to and immediately preceding the application of the agent, the application method, the duration of contact, and the patient's medical history and lifestyle. Various types of peels are discussed. Of particular interest are superficial chemical peels, which offer great flexibility over a range of skin types and conditions with minimal to no "downtime." Alpha-hydroxyacid (AHA) peels are superficial and can be combined with other cosmetic procedures in the office to maximize benefits. In addition, AHA peels work well when combined with supportive homecare products including AHAs or polyhydroxy acids (PHAs), topical retinoids, and antiacne/antirosacea treatments. Case studies are presented of patients using AHA peels for the treatment of acne and hyperpigmentation in a variety of skin types, including Asian skin.

Occupational skin cancer may be underreported

DEFF Research Database (Denmark)

Carøe, Tanja Korfitsen; Ebbehøj, Niels Erik; Wulf, Hans Christian

2013-01-01

Skin cancer may, in some cases, be caused by occupational exposures. The aim of this study was to investigate the prevalence of and exposures leading to occupationally induced skin cancers in Denmark during a ten-year period.......Skin cancer may, in some cases, be caused by occupational exposures. The aim of this study was to investigate the prevalence of and exposures leading to occupationally induced skin cancers in Denmark during a ten-year period....

Idelalisib-induced colitis and skin eruption mimicking graft-versus-host disease.

Science.gov (United States)

Hammami, Muhammad Bader; Al-Taee, Ahmad; Meeks, Marshall; Fesler, Mark; Hurley, M Yadira; Cao, Dengfeng; Lai, Jin-Ping

2017-04-01

Idelalisib is a selective inhibitor of the delta isoform of phosphatidylinositol 3-kinase which was approved by the United States Federal Drug Administration in 2014 for the treatment of relapsed chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Drug-induced injury of the gastrointestinal tract is a relatively frequent but usually under-recognized disease entity. We report the case of a 56-year-old male with a history of relapsed follicular lymphoma status post allogenic bone marrow transplant who developed severe diarrhea with a skin eruption mimicking graft-versus-host disease (GVHD) 6 months after starting idelalisib. He underwent a colonoscopy demonstrating a grossly normal-appearing colon and terminal ileum. Biopsies taken during the procedure revealed mild active ileitis, colitis, and proctitis with frequent epithelial apoptosis, and focal intra-epithelial lymphocytosis. Skin biopsies revealed sub-acute spongiotic dermatitis suggestive of either contact dermatitis or an eczematous drug reaction. Symptoms were attributed to idelalisib given their resolution with withdrawal of the drug in conjunction with the skin and colonic biopsies. High clinical suspicion and awareness of the histological features of idelalisib-associated colitis is important to distinguish it from potential mimickers such as GVHD and infectious colitis.

Topical stabilized retinol treatment induces the expression of HAS genes and HA production in human skin in vitro and in vivo.

Science.gov (United States)

Li, Wen-Hwa; Wong, Heng-Kuan; Serrano, José; Randhawa, Manpreet; Kaur, Simarna; Southall, Michael D; Parsa, Ramine

2017-05-01

Skin Aging manifests primarily with wrinkles, dyspigmentations, texture changes, and loss of elasticity. During the skin aging process, there is a loss of moisture and elasticity in skin resulting in loss of firmness finally leading to skin sagging. The key molecule involved in skin moisture is hyaluronic acid (HA), which has a significant water-binding capacity. HA levels in skin decline with age resulting in decrease in skin moisture, which may contribute to loss of firmness. Clinical trials have shown that topically applied ROL effectively reduces wrinkles and helps retain youthful appearance. In the current study, ROL was shown to induce HA production and stimulates the gene expression of all three forms of hyaluronic acid synthases (HAS) in normal human epidermal keratinocytes monolayer cultures. Moreover, in human skin equivalent tissues and in human skin explants, topical treatment of tissues with a stabilized-ROL formulation significantly induced the gene expression of HAS mRNA concomitant with an increased HA production. Finally, in a vehicle-controlled human clinical study, histochemical analysis confirmed increased HA accumulation in the epidermis in ROL-treated human skin as compared to vehicle. These results show that ROL increases skin expression of HA, a significant contributing factor responsible for wrinkle formation and skin moisture, which decrease during aging. Taken together with the activity to increase collagen, elastin, and cell proliferation, these studies establish that retinol provides multi-functional activity for photodamaged skin.

Monoclonal antibodies reactive with common tumor antigens on UV-induced tumors also react with hyperplastic UV-irradiated skin

International Nuclear Information System (INIS)

Spellman, C.W.; Beauchamp, D.A.

1986-01-01

Most murine skin tumors induced by ultraviolet light (UVB, 280-340 nm) can be successfully transplanted only into syngeneic hosts that have received subcarcinogenic doses of UVB. The tumor susceptible state is long-lived and mediated by T suppressor cells that control effector responses against common antigens on UV-induced tumors. Because antigen specific suppression arises prior to the appearance of a tumor, questions arise about the source of the original antigen. They have previously reported transplantation studies indicating that UV-irradiated skin is antigenically cross-reactive with UV-induced tumors. They now report on flow cytometry analyses showing that a series of MoAb reactive with common antigens expressed by UV-induced tumors are also reactive on cells from UV-irradiated skin. Various antigens appear at different times in the UV irradiation scheme, and some persist while others are transient. They speculate that the common antigens detected may be the ones to which functional suppression is directed. If true, these results suggest that successful tumors need not escape host defenses to emerge. Rather, tumors may arise and grow progressively if they express antigens that cross-react with specificities to which the host has previously mounted a suppressive response

Bee Venom Phospholipase A2 Ameliorates House Dust Mite Extract Induced Atopic Dermatitis Like Skin Lesions in Mice.

Science.gov (United States)

Jung, Kyung-Hwa; Baek, Hyunjung; Kang, Manho; Kim, Namsik; Lee, Seung Young; Bae, Hyunsu

2017-02-18

Atopic dermatitis (AD) is a biphasic inflammatory skin disease that is provoked by epidermal barrier defects, immune dysregulation, and increased skin infections. Previously, we have demonstrated that bvPLA2 evoked immune tolerance by inducing regulatory T cells (Treg), and thus alleviated Th2 dominant allergic asthma in mice. Here, we would like to determine whether treatment with bvPLA2 exacerbates the AD-like allergic inflammations induced by house dust mite extract (DFE) in a murine model. Epidermal thickness, immune cell infiltration, serum immunoglobulin, and cytokines were measured. Ear swelling, skin lesions, and the levels of total serum IgE and Th1/Th2 cytokines were elevated in DFE/DNCB-induced AD mice. Topical application of bvPLA2 elicited significant suppression of the increased AD symptoms, including ear thickness, serum IgE concentration, inflammatory cytokines, and histological changes. Furthermore, bvPLA2 treatment inhibited mast cell infiltration into the ear. On the other hand, Treg cell depletion abolished the anti-atopic effects of bvPLA2, suggesting that the effects of bvPLA2 depend on the existence of Tregs. Taken together, the results revealed that topical exposure to bvPLA2 aggravated atopic skin inflammation, suggesting that bvPLA2 might be a candidate for the treatment of AD.

Photoprotection beyond ultraviolet radiation--effective sun protection has to include protection against infrared A radiation-induced skin damage.

Science.gov (United States)

Schroeder, P; Calles, C; Benesova, T; Macaluso, F; Krutmann, J

2010-01-01

Solar radiation is well known to damage human skin, for example by causing premature skin ageing (i.e. photoageing). We have recently learned that this damage does not result from ultraviolet (UV) radiation alone, but also from longer wavelengths, in particular near-infrared radiation (IRA radiation, 760-1,440 nm). IRA radiation accounts for more than one third of the solar energy that reaches human skin. While infrared radiation of longer wavelengths (IRB and IRC) does not penetrate deeply into the skin, more than 65% of the shorter wavelength (IRA) reaches the dermis. IRA radiation has been demonstrated to alter the collagen equilibrium of the dermal extracellular matrix in at least two ways: (a) by leading to an increased expression of the collagen-degrading enzyme matrix metalloproteinase 1, and (b) by decreasing the de novo synthesis of the collagen itself. IRA radiation exposure therefore induces similar biological effects to UV radiation, but the underlying mechanisms are substantially different, specifically, the cellular response to IRA irradiation involves the mitochondrial electron transport chain. Effective sun protection requires specific strategies to prevent IRA radiation-induced skin damage. 2010 S. Karger AG, Basel.

Arsenic transformation predisposes human skin keratinocytes to UV-induced DNA damage yet enhances their survival apparently by diminishing oxidant response

International Nuclear Information System (INIS)

Sun Yang; Kojima, Chikara; Chignell, Colin; Mason, Ronald; Waalkes, Michael P.

2011-01-01

Inorganic arsenic and UV, both human skin carcinogens, may act together as skin co-carcinogens. We find human skin keratinocytes (HaCaT cells) are malignantly transformed by low-level arsenite (100 nM, 30 weeks; termed As-TM cells) and with transformation concurrently undergo full adaptation to arsenic toxicity involving reduced apoptosis and oxidative stress response to high arsenite concentrations. Oxidative DNA damage (ODD) is a possible mechanism in arsenic carcinogenesis and a hallmark of UV-induced skin cancer. In the current work, inorganic arsenite exposure (100 nM) did not induce ODD during the 30 weeks required for malignant transformation. Although acute UV-treatment (UVA, 25 J/cm 2 ) increased ODD in passage-matched control cells, once transformed by arsenic to As-TM cells, acute UV actually further increased ODD (> 50%). Despite enhanced ODD, As-TM cells were resistant to UV-induced apoptosis. The response of apoptotic factors and oxidative stress genes was strongly mitigated in As-TM cells after UV exposure including increased Bcl2/Bax ratio and reduced Caspase-3, Nrf2, and Keap1 expression. Several Nrf2-related genes (HO-1, GCLs, SOD) showed diminished responses in As-TM cells after UV exposure consistent with reduced oxidant stress response. UV-exposed As-TM cells showed increased expression of cyclin D1 (proliferation gene) and decreased p16 (tumor suppressor). UV exposure enhanced the malignant phenotype of As-TM cells. Thus, the co-carcinogenicity between UV and arsenic in skin cancer might involve adaptation to chronic arsenic exposure generally mitigating the oxidative stress response, allowing apoptotic by-pass after UV and enhanced cell survival even in the face of increased UV-induced oxidative stress and increased ODD. - Highlights: → Arsenic transformation adapted to UV-induced apoptosis. → Arsenic transformation diminished oxidant response. → Arsenic transformation enhanced UV-induced DNA damage.

Caffeine ameliorates radiation-induced skin reactions in mice but does not influence tumour radiation response

Energy Technology Data Exchange (ETDEWEB)

Hebbar, S.A.; Mitra, A.K.; George, K.C.; Verma, N.C. [Radiation Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai (India)]. E-mail: ncverma@apsara.barc.ernet.in

2002-03-01

Intramuscular administration of caffeine at a dose of 80 mg kg{sup -1} body weight to the gastrocnemius muscles of Swiss mice 5 min prior to local irradiation (35 Gy) of the leg delayed the progression of radiation-induced skin reactions in such animals. While 90% epilation with reddening of the skin was noted in animals treated with radiation alone, animals pretreated with caffeine suffered only partial hair loss with slight reddening of the skin on the 16th and 20th days post-irradiation. Beyond the 28th day, damage scores in irradiated feet for both the groups were similar (score 3) and remained unchanged until the 32nd day and then decreased and disappeared completely in both treatment groups by the 40th day after irradiation. In addition, the effect of caffeine on the radiation response of a mouse fibrosarcoma was investigated. Results showed that intratumoral administration of caffeine at a dose of 80 mg kg{sup -1} body weight 5 min prior to local exposure of tumours to 10 Gy of {sup 60}Co {gamma}-rays did not influence the response of tumours to radiation. The present study thus showed that although caffeine ameliorated radiation-induced skin reactions in the mouse leg, it did not affect the tumour radiation response, indicating its potential application in cancer radiotherapy. (author)

Disparate roles of zinc in chemical hypoxia-induced neuronal death

Directory of Open Access Journals (Sweden)

Sujeong eKim

2015-01-01

Full Text Available Accumulating evidence has provided a causative role of zinc (Zn2+ in neuronal death following ischemic brain injury. Using a hypoxia model of primary cultured cortical neurons with hypoxia-inducing chemicals, cobalt chloride (1 mM CoCl2, deferoxamine (3 mM DFX, and sodium azide (2 mM NaN3, we evaluated whether Zn2+ is involved in hypoxic neuronal death. The hypoxic chemicals rapidly elicited intracellular Zn2+ release/accumulation in viable neurons. The immediate addition of the Zn2+ chelator, CaEDTA or N,N,N’N’-tetrakis-(2-pyridylmethyl ethylenediamine (TPEN, prevented the intracellular Zn2+ load and CoCl2-induced neuronal death, but neither 3-hour-later Zn2+ chelation nor a non-Zn2+ chelator ZnEDTA (1 mM demonstrated any effects. However, neither CaEDTA nor TPEN rescued neurons from cell death following DFX- or NaN3-induced hypoxia, whereas ZnEDTA rendered them resistant to the hypoxic injury. Instead, the immediate supplementation of Zn2+ rescued DFX- and NaN3-induced neuronal death. The iron supplementation also afforded neuroprotection against DFX-induced hypoxic injury. Thus, although intracellular Zn2+ release/accumulation is common during chemical hypoxia, Zn2+ might differently influence the subsequent fate of neurons; it appears to play a neurotoxic or neuroprotective role depending on the hypoxic chemical used. These results also suggest that different hypoxic chemicals may induce neuronal death via distinct mechanisms.

Disparate roles of zinc in chemical hypoxia-induced neuronal death.

Science.gov (United States)

Kim, Sujeong; Seo, Jung-Woo; Oh, Shin Bi; Kim, So Hee; Kim, Inki; Suh, Nayoung; Lee, Joo-Yong

2015-01-01

Accumulating evidence has provided a causative role of zinc (Zn(2+)) in neuronal death following ischemic brain injury. Using a hypoxia model of primary cultured cortical neurons with hypoxia-inducing chemicals, cobalt chloride (1 mM CoCl2), deferoxamine (3 mM DFX), and sodium azide (2 mM NaN3), we evaluated whether Zn(2+) is involved in hypoxic neuronal death. The hypoxic chemicals rapidly elicited intracellular Zn(2+) release/accumulation in viable neurons. The immediate addition of the Zn(2+) chelator, CaEDTA or N,N,N'N'-tetrakis-(2-pyridylmethyl) ethylenediamine (TPEN), prevented the intracellular Zn(2+) load and CoCl2-induced neuronal death, but neither 3 hour later Zn(2+) chelation nor a non-Zn(2+) chelator ZnEDTA (1 mM) demonstrated any effects. However, neither CaEDTA nor TPEN rescued neurons from cell death following DFX- or NaN3-induced hypoxia, whereas ZnEDTA rendered them resistant to the hypoxic injury. Instead, the immediate supplementation of Zn(2+) rescued DFX- and NaN3-induced neuronal death. The iron supplementation also afforded neuroprotection against DFX-induced hypoxic injury. Thus, although intracellular Zn(2+) release/accumulation is common during chemical hypoxia, Zn(2+) might differently influence the subsequent fate of neurons; it appears to play a neurotoxic or neuroprotective role depending on the hypoxic chemical used. These results also suggest that different hypoxic chemicals may induce neuronal death via distinct mechanisms.

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

Science.gov (United States)

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 ( Psolar UV spectrum photoprotection; and that the antioxidant property of PCF might play a role in photoprotection.

Mixed chemical-induced oxidative stress in occupational exposure ...

African Journals Online (AJOL)

Mixed chemical-induced oxidative stress in occupational exposure in Nigerians. JI Anetor, SA Yaqub, GO Anetor, AC Nsonwu, FAA Adeniyi, S Fukushima. Abstract. Exposure to single chemicals and associated disorders in occupational environments has received significant attention. Understanding these events holds ...

Sulfur mustard-induced poikiloderma: a case report.

Science.gov (United States)

Emadi, Seyed Naser; Kaffashi, Mohammad; Poursaleh, Zohreh; Akhavan-Moghaddam, Jamal; Soroush, Mohammad Reza; Emadi, Seyed Emad; Taghavi, Nez'hat-o-Sadat

2011-06-01

Sulfur mustard (SM) is a potent chemical warfare agent that was widely used during the First World War and the Iran-Iraq conflict. This vesicant agent causes several acute and chronic effects on the skin, eye, and respiratory system. We report the case of a 41-year-old man who was injured with SM in Iraq chemical attack in 1988. After exposure, he developed severe skin blisters on his upper trunk, dorsum of hands, and genitalia. Based on several clinical observations, such as atrophy, pigmentation, and vascular changes on genitalia with relevant findings in histopathological studies, persistent pigmentation, and damaged skin appendix in hand lesions, a diagnosis of "SM-induced poikiloderma" was postulated. The absence of any complication on the palmar aspect of hands is another remarkable finding in presented case, which suggests a plausible role of the palms as a vector for transporting SM to other sites of the skin.

Papain-induced asthma: diagnosis by skin test, RAST and bronchial provocation test

International Nuclear Information System (INIS)

Baur, X.; Fruhmann, G.

1979-01-01

Seven out of eleven workers occupationally exposed to airborne papain developed immediate hypersensitive reactions, predominantly asthma and rhinitis. Skin tests and RAST with papain were positive in all symptomatic workers, but not in the four asymptomatic workers. Furthermore, out of forty non-exposed asthmatics, thirty-eight had negative RAST results and all had negative skin test results. Bronchial provocation tests with 0.15-0.5 mg papain performed in five patients with a positive case history showed in each case an immediate asthmatic reaction; in addition to that, one patient developed signs of a dual asthmatic reaction. These results suggest that airborne papain is a highly immunogenic agent in humans, which induces type I allergic reactions in a large percentage of the exposed subjects. (author)

TCDD induces dermal accumulation of keratinocyte-derived matrix metalloproteinase-10 in an organotypic model of human skin

Energy Technology Data Exchange (ETDEWEB)

De Abrew, K. Nadira [Molecular and Environmental Toxicology Center, University of Wisconsin—Madison, Madison, WI 53706 (United States); Thomas-Virnig, Christina L.; Rasmussen, Cathy A. [Department of Pathology, University of Wisconsin—Madison, Madison, WI 53706 (United States); Bolterstein, Elyse A. [Molecular and Environmental Toxicology Center, University of Wisconsin—Madison, Madison, WI 53706 (United States); Schlosser, Sandy J. [Department of Pathology, University of Wisconsin—Madison, Madison, WI 53706 (United States); Allen-Hoffmann, B. Lynn, E-mail: blallenh@wisc.edu [Molecular and Environmental Toxicology Center, University of Wisconsin—Madison, Madison, WI 53706 (United States); Department of Pathology, University of Wisconsin—Madison, Madison, WI 53706 (United States)

2014-05-01

The epidermis of skin is the first line of defense against the environment. A three dimensional model of human skin was used to investigate tissue-specific phenotypes induced by the environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Continuous treatment of organotypic cultures of human keratinocytes with TCDD resulted in intracellular spaces between keratinocytes of the basal and immediately suprabasal layers as well as thinning of the basement membrane, in addition to the previously reported hyperkeratinization. These tissue remodeling events were preceded temporally by changes in expression of the extracellular matrix degrading enzyme, matrix metalloproteinase-10 (MMP-10). In organotypic cultures MMP-10 mRNA and protein were highly induced following TCDD treatment. Q-PCR and immunoblot results from TCDD-treated monolayer cultures, as well as indirect immunofluorescence and immunoblot analysis of TCDD-treated organotypic cultures, showed that MMP-10 was specifically contributed by the epidermal keratinocytes but not the dermal fibroblasts. Keratinocyte-derived MMP-10 protein accumulated over time in the dermal compartment of organotypic cultures. TCDD-induced epidermal phenotypes in organotypic cultures were attenuated by the keratinocyte-specific expression of tissue inhibitor of metalloproteinase-1, a known inhibitor of MMP-10. These studies suggest that MMP-10 and possibly other MMP-10-activated MMPs are responsible for the phenotypes exhibited in the basement membrane, the basal keratinocyte layer, and the cornified layer of TCDD-treated organotypic cultures. Our studies reveal a novel mechanism by which the epithelial–stromal microenvironment is altered in a tissue-specific manner thereby inducing structural and functional pathology in the interfollicular epidermis of human skin. - Highlights: • TCDD causes hyperkeratosis and basement membrane changes in a model of human skin. • TCDD induces MMP-10 expression in organotypic cultures

Minimally invasive non-thermal laser technology using laser-induced optical breakdown for skin rejuvenation

NARCIS (Netherlands)

Habbema, L.; Verhagen, R.; Van Hal, R.; Liu, Y.; Varghese, B.

2011-01-01

We describe a novel, minimally invasive laser technology for skin rejuvenation by creating isolated microscopic lesions within tissue below the epidermis using laser induced optical breakdown. Using an in-house built prototype device, tightly focused near-infrared laser pulses are used to create

Microneedle delivery of trivalent influenza vaccine to the skin induces long-term cross-protection.

Science.gov (United States)

Kim, Yeu-Chun; Lee, Su-Hwa; Choi, Won-Hyung; Choi, Hyo-Jick; Goo, Tae-Won; Lee, Ju-Hie; Quan, Fu-Shi

2016-12-01

A painless self-immunization method with effective and broad cross-protection is urgently needed to prevent infections against newly emerging influenza viruses. In this study, we investigated the cross-protection efficacy of trivalent influenza vaccine containing inactivated A/PR/8/34 (H1N1), A/Hong Kong/68 (H3N2) and B/Lee/40 after skin vaccination using microneedle patches coated with this vaccine. Microneedle vaccination of mice in the skin provided 100% protection against lethal challenges with heterologous pandemic strain influenza A/California/04/09, heterogeneous A/Philippines/2/82 and B/Victoria/287 viruses 8 months after boost immunization. Cross-reactive serum IgG antibody responses against heterologous influenza viruses A/California/04/09, A/Philippines/2/82 and B/Victoria/287 were induced at high levels. Hemagglutination inhibition titers were also maintained at high levels against these heterogeneous viruses. Microneedle vaccination induced substantial levels of cross-reactive IgG antibody responses in the lung and cellular immune responses, as well as cross-reactive antibody-secreting plasma cells in the spleen. Viral loads in the lung were significantly (p skin vaccination with trivalent vaccine using a microneedle array could provide protection against seasonal epidemic or new pandemic strain of influenza viruses.

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

DEFF Research Database (Denmark)

Dimitrov, Sabcho; Low, Lawrence; Patlewicz, Grace

2005-01-01

alerting groups, three-dimensional (3D)-QSARs were developed to describe the multiplicity of physicochemical, steric, and electronic parameters. These 3D-QSARs, so-called pattern recognition-type models, were applied each time a latent alerting group was identified in a parent chemical or its generated...... in the model building. The TIssue MEtabolism Simulator (TIMES) software was used to integrate a skin metabolism simulator and 3D-QSARs to evaluate the reactivity of chemicals thus predicting their likely skin sensitization potency....

Successful oral desensitization against skin rash induced by alectinib in a patient with anaplastic lymphoma kinase-positive lung adenocarcinoma: A case report.

Science.gov (United States)

Shirasawa, Masayuki; Kubotaa, Masaru; Harada, Shinya; Niwa, Hideyuki; Kusuhara, Seiichiro; Kasajima, Masashi; Hiyoshi, Yasuhiro; Ishihara, Mikiko; Igawa, Satoshi; Masuda, Noriyuki

2016-09-01

Alectinib has been approved for the treatment of patients with anaplastic lymphoma kinase (ALK) gene rearrangement-positive advanced non-small cell lung cancer. In terms of adverse effects, the occurrence of a severe skin rash induced by alectinib is reportedly rare, compared with the occurrence of skin rash induced by epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). In the present case report, a 76-year-old woman with ALK-positive lung adenocarcinoma experienced disease progression after undergoing first-line chemotherapy. Subsequently, alectinib was administered as a second-line therapy. However, she discontinued alectinib therapy after 11days because of the occurrence of an alectinib-induced skin rash. Since the skin rash improved within one week, we attempted to perform oral desensitization to alectinib. The patient has not shown any recurrence of the rash or disease progression for 7 months since the successful oral desensitization to alectinib. Here, we describe the first case of successful oral desensitization against a skin rash induced by alectinib in a patient with ALK-positive lung adenocarcinoma. Desensitization to overcome adverse effects and to enable sustained treatment with alectinib should be considered in patients who develop alectinib sensitivities. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Mathematical Model to Predict Skin Concentration after Topical Application of Drugs

Directory of Open Access Journals (Sweden)

Hiroaki Todo

2013-12-01

Full Text Available Skin permeation experiments have been broadly done since 1970s to 1980s as an evaluation method for transdermal drug delivery systems. In topically applied drug and cosmetic formulations, skin concentration of chemical compounds is more important than their skin permeations, because primary target site of the chemical compounds is skin surface or skin tissues. Furthermore, the direct pharmacological reaction of a metabolically stable drug that binds with specific receptors of known expression levels in an organ can be determined by Hill’s equation. Nevertheless, little investigation was carried out on the test method of skin concentration after topically application of chemical compounds. Recently we investigated an estimating method of skin concentration of the chemical compounds from their skin permeation profiles. In the study, we took care of “3Rs” issues for animal experiments. We have proposed an equation which was capable to estimate animal skin concentration from permeation profile through the artificial membrane (silicone membrane and animal skin. This new approach may allow the skin concentration of a drug to be predicted using Fick’s second law of diffusion. The silicone membrane was found to be useful as an alternative membrane to animal skin for predicting skin concentration of chemical compounds, because an extremely excellent extrapolation to animal skin concentration was attained by calculation using the silicone membrane permeation data. In this chapter, we aimed to establish an accurate and convenient method for predicting the concentration profiles of drugs in the skin based on the skin permeation parameters of topically active drugs derived from steady-state skin permeation experiments.

Defense against dermal exposures is only skin deep

DEFF Research Database (Denmark)

Nielsen, Jesper Bo; Nielsen, Flemming; Sørensen, Jens Ahm

2007-01-01

study demonstrates that a limited damage to the skin significantly increases the permeability coefficient (K (p)) as well as total percutaneous penetration of chemicals, and most significantly for those compounds that due to their physicochemical characteristics (the most hydrophilic as well as the most...... compartments is affected by the physicochemical characteristics of the chemicals as well as by the integrity of the skin. This observation may have implications when evaluating the possibility of removing chemicals from the skin through different cleansing procedures following unintended dermal exposures....

Chemical stability of reactive skin decontamination lotion (RSDL®).

Science.gov (United States)

Bogan, R; Maas, H J; Zimmermann, T

2018-09-01

Reactive Skin Decontamination Lotion (RSDL ® ) is used for the decontamination of Chemical Warfare Agents and Toxic Industrial Compounds after dermal exposure. It has to be stockpiled over a long period and is handled in all climatic zones. Therefore stability is an essential matter of concern. In this work we describe a study to the chemical stability of RSDL ® as basis for an estimation of shelf life. We analysed RSDL ® for the active ingredient 2,3-butandione monoxime (diacetylmonooxime, DAM), the putative degradation product dimethylglyoxime (DMG) and unknown degradation products by means of a reversed phase high pressure liquid chromatography (HPLC). Calculations were done according to the Arrhenius equation. Based on the temperature dependent rate constants, the time span was calculated, until defined threshold values for DAM and DMG subject to specification and valid regulations were exceeded. The calculated data were compared to the ones gathered from stockpiled samples and samples exposed during foreign mission. The decline of DAM followed first order kinetics, while formation of DMG could be described by zero order kinetics. The rate constants were distinctively temperature dependent. Calculated data were in good accordance to the measured ones from stockpile and mission. Based on a specified acceptable DAM-content of 90% and a valid threshold value of 0.1% (w/w) for the degradation product DMG, RSDL ® proved to be stable for at least four years if stored at the recommended conditions of 15°C-30°C. If continuously stored at higher temperatures shelf life will decrease markedly. Therefore RSDL ® is an object for risk orientated quality monitoring during storage. Copyright © 2017 Elsevier B.V. All rights reserved.

Confocal laser scanning microscopy to estimate nanoparticles' human skin penetration in vitro.

Science.gov (United States)

Zou, Ying; Celli, Anna; Zhu, Hanjiang; Elmahdy, Akram; Cao, Yachao; Hui, Xiaoying; Maibach, Howard

2017-01-01

With rapid development of nanotechnology, there is increasing interest in nanoparticle (NP) application and its safety and efficacy on human skin. In this study, we utilized confocal laser scanning microscopy to estimate NP skin penetration. Three different-sized polystyrene NPs marked with red fluorescence were applied to human skin, and Calcium Green 5N was used as a counterstain. Dimethyl sulfoxide (DMSO) and ethanol were used as alternative vehicles for NPs. Tape stripping was utilized as a barrier-damaged skin model. Skin biopsies dosed with NPs were incubated at 4°C or 37°C for 24 hours and imaged using confocal laser scanning microscopy. NPs were localized in the stratum corneum (SC) and hair follicles without penetrating the epidermis/dermis. Barrier alteration with tape stripping and change in incubation temperature did not induce deeper penetration. DMSO enhanced NP SC penetration but ethanol did not. Except with DMSO vehicle, these hydrolyzed polystyrene NPs did not penetrate intact or barrier-damaged human "viable" epidermis. For further clinical relevance, in vivo human skin studies and more sensitive analytic chemical methodology are suggested.

[The Effectiveness of Cooling Packaging Care in Relieving Chemotherapy-Induced Skin Toxicity Reactions in Cancer Patients Receiving Chemotherapy: A Systematic Review].

Science.gov (United States)

Hsu, Ya-Hui; Hung, Hsing-Wei; Chen, Shu-Ching

2017-08-01

Anti-cancer chemotherapy may cause skin-toxicity reactions. Different types of cooling packages affect chemotherapy-induced skin toxicity reactions differently. To evaluate the effects of cooling packing care on chemotherapy-induced skin toxicity reactions in cancer patients receiving chemotherapy. A systematic review approach was used. Searches were conducted in databases including Cochrane Library, Embase, MEDLINE, PubMed and Airiti Library using the keywords "chemotherapy cutaneous toxicity", "chemotherapy skin reaction", "chemotherapy skin toxicity", "frozen glove", "frozen sock", "cooling packaging care", "ice gloves", "ice socks", "usual care", "severity", "comfort", "satisfaction", "severity", and "comfort". The search focused on articles published before December 2016. Based on the inclusion and exclusion criteria, 5 articles involving relevant randomized controlled trials were extracted for review. Elasto-Gel ice gloves or ice socks that were chilled to -25°C- -30°C and used for 15 mins during initial chemotherapy, for one hour during chemotherapy infusion, and for 15 mins after chemotherapy were shown to improve the frequency and severity of chemotherapy-induced skin toxicity reactions. Several studies were limited by small sample sizes and different types of cooling packing programs, temperature, timing, and frequency. Thus, further research is recommended to verify the effects of cooling packing care. Cancer patients who were treated with docetaxel or PLD and who used ice gloves or ice socks that were chilled to -25°C- -30°C for 15 mins during initial chemotherapy, for one hour during chemotherapy infusion, and for 15 mins after chemotherapy improved significantly in terms of the frequency and severity of their chemotherapy-induced skin toxicity reactions. Local cooling packing care is a non-pharmacotherapy approach that is low cost and free of side effects. This review is intended to provide a reference for clinical care.

Differential gene expression between skin and cervix induced by the E7 oncoprotein in a transgenic mouse model

Science.gov (United States)

Ibarra Sierra, E; Díaz Chávez, J; Cortés-Malagón, EM; Uribe-Figueroa, L; Hidalgo-Miranda, A; Lambert, PF; Gariglio, P

2013-01-01

HPV16 E7 oncoprotein expression in K14E7 transgenic mice induces cervical cancer after 6 months of treatment with the co-carcinogen 17β-estradiol. In untreated mice, E7 also induces skin tumors late in life albeit at low penetrance. These findings indicate that E7 alters cellular functions in cervix and skin so as to predispose these organs to tumorigenesis. Using microarrays, we determined the global genes expression profile in cervical and skin tissue of young adult K14E7 transgenic mice without estrogen treatment. In these tissues, the E7 oncoprotein altered the transcriptional pattern of genes involved in several biological processes including signal transduction, transport, metabolic process, cell adhesion, apoptosis, cell differentiation, immune response and inflammatory response. Among the E7-dysregulated genes were ones not previously known to be involved in cervical neoplasia including DMBT1, GLI1 and 17βHSD2 in cervix, as well as MMP2, 12, 14, 19 and 27 in skin. PMID:22980503

Simulation study and guidelines to generate Laser-induced Surface Acoustic Waves for human skin feature detection

Science.gov (United States)

Li, Tingting; Fu, Xing; Chen, Kun; Dorantes-Gonzalez, Dante J.; Li, Yanning; Wu, Sen; Hu, Xiaotang

2015-12-01

Despite the seriously increasing number of people contracting skin cancer every year, limited attention has been given to the investigation of human skin tissues. To this regard, Laser-induced Surface Acoustic Wave (LSAW) technology, with its accurate, non-invasive and rapid testing characteristics, has recently shown promising results in biological and biomedical tissues. In order to improve the measurement accuracy and efficiency of detecting important features in highly opaque and soft surfaces such as human skin, this paper identifies the most important parameters of a pulse laser source, as well as provides practical guidelines to recommended proper ranges to generate Surface Acoustic Waves (SAWs) for characterization purposes. Considering that melanoma is a serious type of skin cancer, we conducted a finite element simulation-based research on the generation and propagation of surface waves in human skin containing a melanoma-like feature, determine best pulse laser parameter ranges of variation, simulation mesh size and time step, working bandwidth, and minimal size of detectable melanoma.

Efficient intradermal delivery of superoxide dismutase using a combination of liposomes and iontophoresis for protection against UV-induced skin damage.

Science.gov (United States)

Kigasawa, Kaoru; Miyashita, Moeko; Kajimoto, Kazuaki; Kanamura, Kiyoshi; Harashima, Hideyoshi; Kogure, Kentaro

2012-01-01

Superoxide dismutase (SOD) is a potent antioxidant agent that protects against UV-induced skin damage. However, its high molecular weight is a significant obstacle for efficient delivery into the skin through the stratum corneum and development of antioxidant activity. Recently, we developed a non-invasive transfollicular delivery system for macromolecules using a combination of liposomes and iontophoresis, that represents promising technology for enhancing transdermal administration of charged drugs (IJP, 403, 2011, Kajimoto et al.). In this study, in rats we attempted to apply this system to intradermal delivery of SOD for preventing UV-induced skin injury. SOD encapsulating in cationic liposomes was subjected to anodal iontophoresis. After iontophoretic treatment, the liposomes were diffused widely in the viable skin layer around hair follicles. In contrast, passive diffusion failed to transport liposomes efficiently into the skin. Iontophoretic delivery of liposomes encapsulating SOD caused a marked decrease in the production of oxidative products, such as malondialdehyde, hexanoyl lysine, and 8-hydroxi-2-deoxyguanosine, in UV-irradiated skin. These findings suggested that functional SOD can be delivered into the skin using a combination of iontophoresis and a liposomal system. In conclusion, we succeeded in developing an efficient intradermal SOD delivery system, that would be useful for delivery of other macromolecules.

Gravimetric analysis and differential scanning calorimetric studies on glycerin-induced skin hydration.

Science.gov (United States)

Lee, Ae-Ri Cho; Moon, Hee Kyung

2007-11-01

A thermal gravimetric analysis (TGA) and a differential scanning calorimetry (DSC) were carried out to characterize the water property and an alteration of lipid phase transition of stratum corneum (SC) by glycerin. In addition, the relationship between steady state skin permeation rate and skin hydration in various concentrations of glycerin was investigated. Water vapor absorption-desorption was studied in the hairless mouse stratum corneum. Dry SC samples were exposed to different conc. of glycerin (0-50%) followed by exposure to dry air and the change in weight property was monitored over time by use of TGA. In DSC study, significant decrease in DeltaH of the lipid transition in 10% glycerin and water treated sample: the heat of lipid transition of normal, water, 10% glycerin treated SC were 6.058, 4.412 and 4.316 mJ/mg, respectively. In 10% glycerin treated SCs, the Tc of water shifts around 129 degrees C, corresponding to the weakly bound secondary water. In 40% glycerin treated SC, the Tc of water shifts to 144 degrees C corresponding to strongly bound primary water. There was a good correlation between the hydration property of the skin and the steady state skin flux with the correlation coefficient (r2=0.94). As the hydration increased, the steady state flux increased. As glycerin concentration increased, hydration property decreased. High diffusivity induced by the hydration effect of glycerin and water could be the major contributing factor for the enhanced skin permeation of nicotinic acid (NA).

Skin tribology: Science friction?

NARCIS (Netherlands)

van der Heide, Emile; Zeng, Xiangqiong; Masen, Marc Arthur

2013-01-01

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

Comparative evaluation of differential laser-induced perturbation spectroscopy as a technique to discriminate emerging skin pathology

Science.gov (United States)

Kozikowski, Raymond T.; Smith, Sarah E.; Lee, Jennifer A.; Castleman, William L.; Sorg, Brian S.; Hahn, David W.

2012-06-01

Fluorescence spectroscopy has been widely investigated as a technique for identifying pathological tissue; however, unrelated subject-to-subject variations in spectra complicate data analysis and interpretation. We describe and evaluate a new biosensing technique, differential laser-induced perturbation spectroscopy (DLIPS), based on deep ultraviolet (UV) photochemical perturbation in combination with difference spectroscopy. This technique combines sequential fluorescence probing (pre- and post-perturbation) with sub-ablative UV perturbation and difference spectroscopy to provide a new spectral dimension, facilitating two improvements over fluorescence spectroscopy. First, the differential technique eliminates significant variations in absolute fluorescence response within subject populations. Second, UV perturbations alter the extracellular matrix (ECM), directly coupling the DLIPS response to the biological structure. Improved biosensing with DLIPS is demonstrated in vivo in a murine model of chemically induced skin lesion development. Component loading analysis of the data indicates that the DLIPS technique couples to structural proteins in the ECM. Analysis of variance shows that DLIPS has a significant response to emerging pathology as opposed to other population differences. An optimal likelihood ratio classifier for the DLIPS dataset shows that this technique holds promise for improved diagnosis of epithelial pathology. Results further indicate that DLIPS may improve diagnosis of tissue by augmenting fluorescence spectra (i.e. orthogonal sensing).

Skin barrier function

DEFF Research Database (Denmark)

2016-01-01

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

Bee Venom Phospholipase A2 Ameliorates House Dust Mite Extract Induced Atopic Dermatitis Like Skin Lesions in Mice

Directory of Open Access Journals (Sweden)

Kyung-Hwa Jung

2017-02-01

Full Text Available Atopic dermatitis (AD is a biphasic inflammatory skin disease that is provoked by epidermal barrier defects, immune dysregulation, and increased skin infections. Previously, we have demonstrated that bvPLA2 evoked immune tolerance by inducing regulatory T cells (Treg, and thus alleviated Th2 dominant allergic asthma in mice. Here, we would like to determine whether treatment with bvPLA2 exacerbates the AD-like allergic inflammations induced by house dust mite extract (DFE in a murine model. Epidermal thickness, immune cell infiltration, serum immunoglobulin, and cytokines were measured. Ear swelling, skin lesions, and the levels of total serum IgE and Th1/Th2 cytokines were elevated in DFE/DNCB-induced AD mice. Topical application of bvPLA2 elicited significant suppression of the increased AD symptoms, including ear thickness, serum IgE concentration, inflammatory cytokines, and histological changes. Furthermore, bvPLA2 treatment inhibited mast cell infiltration into the ear. On the other hand, Treg cell depletion abolished the anti-atopic effects of bvPLA2, suggesting that the effects of bvPLA2 depend on the existence of Tregs. Taken together, the results revealed that topical exposure to bvPLA2 aggravated atopic skin inflammation, suggesting that bvPLA2 might be a candidate for the treatment of AD.

Melanin Transfer in Human 3D Skin Equivalents Generated Exclusively from Induced Pluripotent Stem Cells.

Science.gov (United States)

Gledhill, Karl; Guo, Zongyou; Umegaki-Arao, Noriko; Higgins, Claire A; Itoh, Munenari; Christiano, Angela M

2015-01-01

The current utility of 3D skin equivalents is limited by the fact that existing models fail to recapitulate the cellular complexity of human skin. They often contain few cell types and no appendages, in part because many cells found in the skin are difficult to isolate from intact tissue and cannot be expanded in culture. Induced pluripotent stem cells (iPSCs) present an avenue by which we can overcome this issue due to their ability to be differentiated into multiple cell types in the body and their unlimited growth potential. We previously reported generation of the first human 3D skin equivalents from iPSC-derived fibroblasts and iPSC-derived keratinocytes, demonstrating that iPSCs can provide a foundation for modeling a complex human organ such as skin. Here, we have increased the complexity of this model by including additional iPSC-derived melanocytes. Epidermal melanocytes, which are largely responsible for skin pigmentation, represent the second most numerous cell type found in normal human epidermis and as such represent a logical next addition. We report efficient melanin production from iPSC-derived melanocytes and transfer within an entirely iPSC-derived epidermal-melanin unit and generation of the first functional human 3D skin equivalents made from iPSC-derived fibroblasts, keratinocytes and melanocytes.

Melanin Transfer in Human 3D Skin Equivalents Generated Exclusively from Induced Pluripotent Stem Cells.

Directory of Open Access Journals (Sweden)

Karl Gledhill

Full Text Available The current utility of 3D skin equivalents is limited by the fact that existing models fail to recapitulate the cellular complexity of human skin. They often contain few cell types and no appendages, in part because many cells found in the skin are difficult to isolate from intact tissue and cannot be expanded in culture. Induced pluripotent stem cells (iPSCs present an avenue by which we can overcome this issue due to their ability to be differentiated into multiple cell types in the body and their unlimited growth potential. We previously reported generation of the first human 3D skin equivalents from iPSC-derived fibroblasts and iPSC-derived keratinocytes, demonstrating that iPSCs can provide a foundation for modeling a complex human organ such as skin. Here, we have increased the complexity of this model by including additional iPSC-derived melanocytes. Epidermal melanocytes, which are largely responsible for skin pigmentation, represent the second most numerous cell type found in normal human epidermis and as such represent a logical next addition. We report efficient melanin production from iPSC-derived melanocytes and transfer within an entirely iPSC-derived epidermal-melanin unit and generation of the first functional human 3D skin equivalents made from iPSC-derived fibroblasts, keratinocytes and melanocytes.

Molecular Insights into SIRT1 Protection Against UVB-Induced Skin Fibroblast Senescence by Suppression of Oxidative Stress and p53 Acetylation.

Science.gov (United States)

Chung, Ki Wung; Choi, Yeon Ja; Park, Min Hi; Jang, Eun Ji; Kim, Dae Hyun; Park, Byung Hyun; Yu, Byung Pal; Chung, Hae Young

2015-08-01

Stresses, such as exposure to ultraviolet radiation and those associated with aging, are known to cause premature cellular senescence that is characterized by growth arrest and morphological and gene expression changes. This study was designed to investigate the protective effect of Sirtuin1 (SIRT1) on the UVB-induced premature senescence. Under in vitro experimental conditions, exposure to a subcytotoxic dose of UVB enhanced human skin fibroblasts senescence, as characterized by increased β-galactosidase activity and increased levels of senescence-associated proteins. However, adenovirus-mediated SIRT1 overexpression significantly protected fibroblasts from UVB-induced cellular deterioration. Exposure to UVB-induced cell senescence was associated with oxidative stress and p38 mitogen-activated protein kinase activation. Molecular analysis demonstrated that deacetylation of Forkhead box O3α (FOXO3α) by SIRT1 changed the transcriptional activity of FOXO3α and increased resistance to the oxidative stress. In addition, SIRT1 suppressed UVB-induced p53 acetylation and its transcriptional activity, which directly affected the cell cycle arrest induced by UVB. Further study demonstrated that SIRT1 activation inhibited cell senescence in the skin of the HR1 hairless mouse exposed to UVB. The study identifies a new role for SIRT1 in the UVB-induced senescence of skin fibroblats and provides a potential target for skin protection through molecuar insights into the mechanisms responsible for UVB-induced photoaging. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Comparison of protocols for measuring cosmetic ingredient distribution in human and pig skin.

Science.gov (United States)

Gerstel, D; Jacques-Jamin, C; Schepky, A; Cubberley, R; Eilstein, J; Grégoire, S; Hewitt, N; Klaric, M; Rothe, H; Duplan, H

2016-08-01

The Cosmetics Europe Skin Bioavailability and Metabolism Task Force aims to improve the measurement and prediction of the bioavailability of topically-exposed compounds for risk assessment. Key parameters of the experimental design of the skin penetration studies were compared. Penetration studies with frozen human and pig skin were conducted in two laboratories, according to the SCCS and OECD 428 guidelines. The disposition in skin was measured 24h after finite topical doses of caffeine, resorcinol and 7-ethoxycoumarin. The bioavailability distribution in skin layers of cold and radiolabelled chemicals were comparable. Furthermore, the distribution of each chemical was comparable in human and pig skin. The protocol was reproducible across the two laboratories. There were small differences in the amount of chemical detected in the skin layers, which were attributed to differences in washing procedures and anatomical sites of the skin used. In conclusion, these studies support the use of pig skin as an alternative source of skin should the availability of human skin become a limiting factor. If radiolabelled chemicals are not available, cold chemicals can be used, provided that the influence of chemical stability, reactivity or metabolism on the experimental design and the relevance of the data obtained is considered. Copyright © 2016. Published by Elsevier Ltd.

WE-FG-202-01: Early Prediction of Radiotherapy Induced Skin Reactions Using Dynamic Infrared Imaging

Energy Technology Data Exchange (ETDEWEB)

Biswal, N [Rutgers Cancer Institute of New Jersey, New Brunswick, NJ (United States); Cifter, G [Boston, MA (United States); Sun, J [Argonne National Laboratory, Lemont, IL (United States); Sen, N; Wang, D; Diaz, A; Griem, K [Rush University Medical Center, Chicago, IL (United States); Chu, J [Rush University Medical Center, Oak Brook, IL (United States)

2016-06-15

Purpose: To predict radiotherapy induced skin reactions using dynamic infrared imaging. Methods: Thermal images were captured by our homebuilt system consisting of two flash lamps and an infrared (IR) camera. The surface temperature of the skin was first raised by ∼ 6 oC from ∼1 ms flashes. The camera then captured a series of IR images for 10 seconds. For each image, a baseline skin temperature was recorded for 0.5sec before heat impulse. The temporal temperature gradients were calculated between a reference point (immediately after the flash) and at a time point 9sec after that. Thermal effusivity, an intrinsic thermal property of a material, was calculated from the surface temperature decay of skin. We present experimental data in five patients undergoing radiation therapy, of which 2 were Head & Neck, 1 was Sarcoma and 2 were Breast cancer patients. The prescribed doses were 45 – 60 Gy in 25 – 30 fractions. Each patient was imaged before treatment and after every fifth fraction until end of the treatment course. An area on the skin, outside the radiation field, was imaged as control region. During imaging, each patient’s irradiated skins were scored based on RTOG skin morbidity scoring criteria. Results: Temperature gradient, which is the temperature recovery rate, depends on the thermal properties of underlying tissue. It was observed that, the skin temperature and temporal temperature gradient increases with delivered radiation dose and skin RTOG score. The treatment does not change effusivity of superficial skin layer, however there was a significant difference in effusivity between treated and control areas at depth of ∼ 1.5 – 1.8 mm, increases with dose. Conclusion: The higher temporal temperature gradient and effusivity from irradiated areas suggest that there is more fluid under the irradiated skin, which causes faster temperature recovery. The mentioned effects may be predictors of Moist Desquamation.

Proteomic profiling reveals candidate markers for arsenic-induced skin keratosis.

Science.gov (United States)

Guo, Zhiling; Hu, Qin; Tian, Jijing; Yan, Li; Jing, Chuanyong; Xie, Heidi Qunhui; Bao, Wenjun; Rice, Robert H; Zhao, Bin; Jiang, Guibin

2016-11-01

Proteomics technology is an attractive biomarker candidate discovery tool that can be applied to study large sets of biological molecules. To identify novel biomarkers and molecular targets in arsenic-induced skin lesions, we have determined the protein profile of arsenic-affected human epidermal stratum corneum by shotgun proteomics. Samples of palm and foot sole from healthy subjects were analyzed, demonstrating similar protein patterns in palm and sole. Samples were collected from the palms of subjects with arsenic keratosis (lesional and adjacent non-lesional samples) and arsenic-exposed subjects without lesions (normal). Samples from non-exposed healthy individuals served as controls. We found that three proteins in arsenic-exposed lesional epidermis were consistently distinguishably expressed from the unaffected epidermis. One of these proteins, the cadherin-like transmembrane glycoprotein, desmoglein 1 (DSG1) was suppressed. Down-regulation of DSG1 may lead to reduced cell-cell adhesion, resulting in abnormal epidermal differentiation. The expression of keratin 6c (KRT6C) and fatty acid binding protein 5 (FABP5) were significantly increased. FABP5 is an intracellular lipid chaperone that plays an essential role in fatty acid metabolism in human skin. This raises a possibility that overexpression of FABP5 may affect the proliferation or differentiation of keratinocytes by altering lipid metabolism. KRT6C is a constituent of the cytoskeleton that maintains epidermal integrity and cohesion. Abnormal expression of KRT6C may affect its structural role in the epidermis. Our findings suggest an important approach for future studies of arsenic-mediated toxicity and skin cancer, where certain proteins may represent useful biomarkers of early diagnoses in high-risk populations and hopefully new treatment targets. Further studies are required to understand the biological role of these markers in skin pathogenesis from arsenic exposure. Copyright © 2016 Elsevier Ltd

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

International Nuclear Information System (INIS)

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

2014-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

Pratheeshkumar, Poyil; Son, Young-Ok; Wang, Xin; Divya, Sasidharan Padmaja [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Joseph, Binoy [Spinal Cord and Brain Injury Research Center and Department of Physiology, University of Kentucky, Lexington, KY 40536-0509 (United States); Hitron, John Andrew; Wang, Lei [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Kim, Donghern [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Yin, Yuanqin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Cancer Institute, The First Affiliated Hospital, China Medical University, Shenyang (China); Roy, Ram Vinod [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Lu, Jian [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Institute of Life Sciences, Jiangsu University, Zhenjiang, Jiangsu 212013 (China); Zhang, Zhuo [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Wang, Yitao [State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau (China); and others

2014-10-01

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

Modulation of radio-induced oxidative damage by the combination of pentoxifylline and γ-tocopherol in skin fibroblasts and microvascular endothelial cells

International Nuclear Information System (INIS)

Laurent, Carine; Roy, Laurence; Voisin, Philippe; Pouget, JeanPierre

2004-01-01

Clinical or accidental localized ionizing radiation exposure can induce severe skin damage constituting the cutaneous radiological syndrome which is divided in acute and late phases. The combination of pentoxifylline (PTX), antioxidant phytochemical, and γ-tocopherol, antioxidant nutrient shows effectiveness in reducing the late radio-induced skin damage with a long period. This work aims to investigate the molecular and cellular mechanisms involved in the effects of this combination