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1.
Anticancer Res ; 40(2): 719-722, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014913

RESUMO

AIM: A commercially available light emitting diode (LED) that transmitted narrow band ultraviolet B (UVB) radiation was evaluated for its efficacy and efficiency to produce vitamin D3 in human skin. MATERIALS AND METHODS: Human skin samples were obtained from surgical procedures. The LED had peak emission wavelength of 295 nm. Skin samples were exposed to the UVB-LED for varying times and then were analyzed by high-pressure liquid chromatography (HPLC) to determine the vitamin D3 content. RESULTS: There was a statistically significant time- and dose-dependent increase in the percent of 7-dehydrocholesterol that was converted to vitamin D3 in the skin type II samples; 1.3%±0.5, 2.3%±0.6 and 4.5%±1.67 after exposure to 0.75 (11.7 mJ/cm2), 1.5 (23.4 mJ/cm2) and 3 (46.8 mJ/cm2) minimal erythemal doses (MEDs), respectively. CONCLUSION: The UVB-LED was effective and efficient in generating vitamin D3 in human skin, in vitro. The amount of vitamin D3 production increased in a dose-dependent fashion with increased UVB energy. UVB-LEDs can be developed for devices that can efficiently produce vitamin D3 in human skin.


Assuntos
Colecalciferol/biossíntese , Pele/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta , Colecalciferol/metabolismo , Cromatografia Líquida de Alta Pressão , Desidrocolesteróis/metabolismo , Relação Dose-Resposta à Radiação , Humanos
2.
Anticancer Res ; 40(1): 511-518, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892606

RESUMO

BACKGROUND/AIM: This review examined the implications of using sunscreen photoprotection on 25(OH)D formation and determined the best photoprotective method to reduce the risk of skin cancer caused by ultraviolet radiation (UVR). Based on previous studies on 25(OH)D formation after use of different amounts of sunscreen and different doses of UVR for approximately one week to different body areas it is possible to estimate the amount of 25(OH)D formed after a week's holiday in Southern and Northern Europe. CONCLUSION: The best method of photoprotection by sunscreen is two consecutive applications before sun exposure, ensuring the use of sufficient amounts of sunscreen and minimizing the unprotected skin areas. The double application method simultaneously ensures a high photoprotection against erythema from sun exposure. Despite the use of sunscreen, the calculated serum 25(OH)D levels clearly increase to similar levels as those measured after sun vacations.


Assuntos
Protetores Solares/farmacologia , Vitamina D/análogos & derivados , Humanos , Pele/efeitos da radiação , Banho de Sol , Raios Ultravioleta , Vitamina D/metabolismo , Organização Mundial da Saúde
3.
Anticancer Res ; 40(1): 565-572, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892613

RESUMO

BACKGROUND/AIM: To assess the effectiveness of three UV emitting lamps on the cutaneous production of vitamin D3, a marker of DNA damage and nitric oxide production in human skin. MATERIALS AND METHODS: Human skin samples (skin types II, III and IV) obtained from surgery were exposed to three different UV emitting lamps for varying times and then extracted and chromatographed to determine the vitamin D3 content. The skin samples exposed to the 3 UV emitting lamps were also evaluated for 8-hydroxy-2'-deoxyguanosine (a marker of DNA damage) and nitric oxide production. RESULTS: It was observed that the spectral output of the 3 lamps had different effects on the cutaneous production of vitamin D3, 8-hydroxy-2'-deoxyguanosine and nitric oxide production. One lamp demonstrated optimal production of vitamin D3 with the least amount of DNA damage and intermediate production of nitric oxide suggesting that it could be developed into a device for treating vitamin D deficiency. CONCLUSION: The spectral output of the experimental UVB emitting lamps significantly influenced the cutaneous production of vitamin D3 8-hydroxy-2'-deoxyguanosine and nitric oxide.


Assuntos
/biossíntese , Colecalciferol/biossíntese , Óxido Nítrico/biossíntese , Pele/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta , Relação Dose-Resposta à Radiação , Eritema/etiologia , Humanos
4.
Immunology ; 159(2): 133-141, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31593303

RESUMO

The majority of human vaccines are administered above the deltoid muscle of the arm, a site that is chronically sun-exposed in many people. It is known that exposure of the skin to the UV wavelengths in sunlight stimulates systemic immunosuppression, an outcome that is associated with reduced immunity to microbial infections in animal models. Here we consider whether immunization of humans through a UV-irradiated skin site will lead to a less effective immune response compared with immunization through an unexposed site. Studies showing that the efficacy of vaccination can be reduced when surrogates of increased levels of sun exposure, such as latitude of residence and season of the year, are considered. Results from a limited number of intervention experiments in humans demonstrate a similar pattern. To provide an explanation for these findings, changes in the number and functional potential of immune cells in chronically sun-exposed compared with unexposed skin are outlined. UV radiation-induced changes to skin cells are also relevant when considering skin sites for administration of immune-tolerizing peptides. The review provides the basis for further research into the effects of acute and chronic UV radiation exposure on skin cells in the context of vaccination.


Assuntos
Tolerância Imunológica/efeitos da radiação , Imunogenicidade da Vacina , Pele/efeitos da radiação , Luz Solar , Vacinação , Vacinas/administração & dosagem , Animais , Células Dendríticas/imunologia , Células Dendríticas/efeitos da radiação , Humanos , Memória Imunológica/efeitos da radiação , Injeções Intradérmicas , Mastócitos/imunologia , Mastócitos/efeitos da radiação , Estações do Ano , Pele/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos da radiação
5.
Int J Radiat Oncol Biol Phys ; 106(3): 514-524, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31756414

RESUMO

PURPOSE: To compare single-stage direct-to-implant (DTI) immediate reconstruction to the commonly used 2-stages expander and implant (TE/I) or autologous reconstruction with focus on postmastectomy radiation therapy (PMRT) setting. METHODS AND MATERIALS: We reviewed the charts of 1,286 patients who underwent 1,814 breast reconstructions at our institution with and without PMRT from 1997 to 2017. Patients were divided into 6 groups according to type of reconstruction and PMRT status. Primary objective was reconstruction complications defined solely on surgical reintervention operative notes such as infection, skin necrosis, and fat necrosis across all groups. Implant-related complications such as capsular contracture, implant rupture or exposure, or implant failure were compared between TE/I and DTI. Kaplan-Meier estimates were used to calculate 5-year cumulative incidence of complications. The secondary objective was to compare the 3 reconstruction types in settings of immediate reconstruction followed by PMRT on multivariable analysis. RESULTS: Median follow-up was 5.8 years. Among 1286 patients, 41.1% (N = 529/1286) received PMRT. Among 1814 reconstructed breasts, autologous, single-stage, and TE/I represented 18.7%, 34.8%, and 46.2%, respectively. With no PMRT, the 5-year cumulative incidence of any reconstruction complication was 11.1%, 12.6%, and 19.5% for autologous, DTI, and TE/I reconstructions, respectively. The addition of PMRT resulted in 5-year cumulative incidence of 15.1%, 18.2%, and 36.8%, respectively. The multivariable analysis showed that DTI was associated with lesser complications compared with TE/I, whereas no significant difference was noted between DTI and autologous. CONCLUSIONS: Single-stage DTI reconstruction had significantly lower complication rates than TE/I with and without PMRT. Single-stage complication rates were not significantly different from autologous complication rates in PMRT settings. Single-stage reconstruction may offer a valuable option for patients receiving PMRT.


Assuntos
Implante Mamário/efeitos adversos , Implantes de Mama/efeitos adversos , Neoplasias da Mama/radioterapia , Mamoplastia/efeitos adversos , Complicações Pós-Operatórias , Dispositivos para Expansão de Tecidos/efeitos adversos , Neoplasias da Mama/cirurgia , Feminino , Humanos , Incidência , Mamoplastia/métodos , Mamoplastia/estatística & dados numéricos , Pessoa de Meia-Idade , Necrose , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/epidemiologia , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/estatística & dados numéricos , Estudos Retrospectivos , Pele/patologia , Pele/efeitos da radiação , Fatores de Tempo
6.
J Surg Res ; 245: 483-491, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31446190

RESUMO

BACKGROUND: This study investigated the efficacy of extracorporeal shock wave (ESW) application in stimulating dermal thickness, vascularity, and collagen synthesis of facial skin in a large animal model. MATERIALS AND METHODS: The facial skin of the maxillary and mandibular areas of goats (n = 6 per group) was treated with ESWs of different intensities (0.15 and 0.45 mJ/mm2; 1000 pulses). After 4 d, histology and immunohistochemistry were used to evaluate the following: dermal thickness, total number and abundance of microvessels, amount of type 1 collagen, and α-smooth muscle actin expression. RESULTS: Dermal thickness, number and abundance of microvessels, and collagen synthesis increased after ESW application at both intensities (each P < 0.05). When comparing ESW groups, the highest collagen abundance was seen after 0.15 mJ/mm2 (P = 0.034), whereas the highest number of microvessels was detected after treatment with 0.45 mJ/mm2 (P = 0.002). CONCLUSIONS: A single-session application of focused low-energy ESWs to facial skin can increase dermal thickness by stimulating collagen production and local microcirculation. These findings commend the technique for future investigation for pretreatment of local or microvascular skin flaps to enhance tissue healing.


Assuntos
Colágeno/metabolismo , Face/cirurgia , Ondas de Choque de Alta Energia/uso terapêutico , Neovascularização Fisiológica/efeitos da radiação , Pele/efeitos da radiação , Animais , Modelos Animais de Doenças , Cabras , Humanos , Masculino , Modelos Animais , Pele/irrigação sanguínea , Pele/metabolismo , Retalhos Cirúrgicos/irrigação sanguínea , Ferida Cirúrgica/radioterapia , Cicatrização/efeitos da radiação
7.
Dermatol Surg ; 45(11): 1401-1405, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31658188

RESUMO

BACKGROUND: Current treatment options for rosacea include topical agents, oral therapies, phototherapy using lasers, or intense pulsed light (IPL). Combination therapy for rosacea often yields better results than monotherapy. The safety of laser/light treatments in combination with systemic doxycycline has been questioned because of the theoretical risk of photosensitivity. OBJECTIVE: The purpose of this study was to assess the incidence of phototoxicity or photosensitivity in rosacea patients receiving concomitant laser or light treatments and systemic doxycycline. METHODS: Treatment records of 36 patients receiving laser/light treatments while also being treated with standard dose or anti-inflammatory dose of doxycycline were retrospectively reviewed. RESULTS: No adverse reactions related to doxycycline combined with laser/light therapy were reported. Specifically, no photosensitivity or sensitivity to wavelengths in the pulsed dye laser (PDL), or IPL range was observed in this cohort. All patients achieved some degree of clearance. CONCLUSION: The results of this retrospective study demonstrate that doxycycline used in conjunction with laser or nonlaser light therapy is a valid combination therapy for improving signs and symptoms of rosacea. No photosensitivity reactions were observed to commonly used IPL or PDL devices.


Assuntos
Antibacterianos/efeitos adversos , Doxiciclina/efeitos adversos , Terapia de Luz Pulsada Intensa/efeitos adversos , Terapia com Luz de Baixa Intensidade/efeitos adversos , Rosácea/terapia , Administração Cutânea , Adolescente , Adulto , Idoso , Antibacterianos/administração & dosagem , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/efeitos adversos , Doxiciclina/administração & dosagem , Feminino , Humanos , Terapia de Luz Pulsada Intensa/instrumentação , Terapia de Luz Pulsada Intensa/métodos , Lasers de Corante/efeitos adversos , Terapia com Luz de Baixa Intensidade/métodos , Masculino , Pessoa de Meia-Idade , Transtornos de Fotossensibilidade/diagnóstico , Transtornos de Fotossensibilidade/etiologia , Estudos Retrospectivos , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Resultado do Tratamento , Adulto Jovem
8.
Chem Commun (Camb) ; 55(80): 12036-12039, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31531454

RESUMO

While commercially available suncare products are effective at absorbing ultraviolet (UV)-light, recent studies indicate systemic toxicities associated with many traditional chemical and physical UV-filters. We demonstrate the application of xanthommatin, a biochrome present in arthropods and cephalopods, as an alternative chemical UV-filter that is cytocompatible while maintaining its photostability and photoprotective properties.


Assuntos
Antioxidantes/farmacologia , Oxazinas/farmacologia , Pele/efeitos da radiação , Protetores Solares/farmacologia , Xantenos/farmacologia , Animais , Antioxidantes/química , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Dimetilpolisiloxanos/química , Humanos , Camundongos , Células NIH 3T3 , Oxazinas/química , Estudo de Prova de Conceito , Pele/citologia , Protetores Solares/química , Raios Ultravioleta , Xantenos/química
9.
Pak J Pharm Sci ; 32(3 Special): 1387-1393, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31551220

RESUMO

The histological and ultrastructural changes of skin of Wistar rats were compared with 10600nm CO2 dot laser irradiation and external use of A acid preparation. The effects of dot matrix CO2 laser and Nd: YAG laser (quasi long pulse width 10600nm wavelength) on the expression of matrix metalloproteinase -1 (MMP-1) and matrix metalloproteinase inhibitor -1 (TIMP-1) in skin of natural aging mice were investigated, and the skin tender mechanism was further explored. To explore the long-term efficacy and timeliness of 10600nm CO2 dot laser and A acid treatment, so as to provide reference for clinical practice. The skin of hair on the back of mice was irradiated with dot CO2 laser and Nd: YAG laser. They were taken at 2 weeks, 1 month and 3 months after irradiation respectively. The dynamic changes of skin HSP47, HSP70 and TGF - ß 1 were detected by immunohistochemistry, and the difference of two laser irradiation effects was compared. 45 female Wistar rats were randomly divided into 9 groups. The back skin was used as the experimental observation area. After the depilation, the observation was divided into four parts by using the cross shaped marking line: the left side of the proximal end was the normal control group (A area). At the proximal end, the left side was the vitamin A acid group (B area). The right side of the tail was the combined treatment group (C area), and the right side of the proximal end was the dot laser group (D area). The C and D regions irradiated 10600 CO2 dot matrix laser 1 times at the beginning of the experiment. The parameters were: energy 15mJ, energy density 5%, frequency 300Hz. The fig. is square, 10mm * 10mm; after the laser irradiation, the B and C areas begin to wipe the 0.025% dimensional A cream every day for 3 weeks. The positive expression of MMP-1 and TIMP-1 in dot CO2 laser and Nd: YAG laser irradiation area was most obvious at 2 weeks. The MMP-1 gray value (115.14 + 5.23) and TIMP-1 gray value (104.01 + 3.15) of the dot matrix laser irradiated area were lower than the MMP-1 gray value (121.75 + 4.39) and TIMP-1 gray value (109.26 + 3.88) in the Nd: YAG laser irradiation area. That is, the positive expression of CO2 laser irradiation area was higher, and the difference was statistically significant (P < 0.05).


Assuntos
Hidroxiprolina/metabolismo , Lasers de Gás/uso terapêutico , Pele/efeitos da radiação , Envelhecimento , Animais , Feminino , Proteínas de Choque Térmico HSP47/metabolismo , Lasers de Estado Sólido , Metaloproteinase 13 da Matriz/metabolismo , Camundongos , Pele/metabolismo , Pele/ultraestrutura , Inibidor Tecidual de Metaloproteinase-1/metabolismo
10.
Phys Med ; 66: 77-87, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31563728

RESUMO

OBJECTIVE: To assess the interactive Skin Dose Map® tool (SDMTool) integrated to the radiation dose management system (RDMS) DoseWatch® with Gafchromic® films for implementation in routine practice. METHODS: A retrospective dose estimation software SDMTool was used to calculate Peak Skin Dose (PSD) and display the patient skin dose distribution. PSD was calculated with a triangle mesh of 0.055 cm2 resolution on ICRP 110 male anthropomorphic phantom and with a square ROI of 1 cm2 on flat phantom. The tool uses Radiation Dose Structured Reports (RDSR) data to model exposure events and calculate the PSD per event. The PSD and the skin dose distribution estimated with SDMTool were evaluated in comparison with Gafchromic® films positioned under the PMMA phantom (20 cm) for 13 configurations. Measurements were performed on a Philips system. Statistical analysis were carried out to compare PSDFilm and PSDSDM. RESULTS: Average differences between PSDFilm and PSDSDM were 6% ±â€¯6% (range from -3% to 22%) for flat phantom and 5% ±â€¯7% (range from -3% to 25%) for ICRP phantom. Concordance was good between the measured PSDFilm and the estimated PSDSDM with Lin's coefficient estimation and 95% Confidence Interval of 0.979 [0.875; 0.984] for flat phantom and 0.977 [0.877; 0.985] for ICRP phantom. Dose map representations are concordant for 11 of the 13 tests on PMMA phantom. Disparities arose from the limitations of the RSDR format: table displacement during fluoroscopy events and the use of wedge filter. CONCLUSION: The results found in this experimental evaluation show that the SDMTool is a suitable alternative to Gafchromic® film to calculate PSD.


Assuntos
Dosimetria Fotográfica/instrumentação , Doses de Radiação , Pele/efeitos da radiação , Imagens de Fantasmas , Software
11.
J Microbiol Biotechnol ; 29(9): 1349-1360, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31474086

RESUMO

Chronic exposure to ultraviolet (UV) radiation, regarded as a major cause of extrinsic aging or photoaging characterized by wrinkle formation and skin dehydration, exerts adverse effects on skin by causing the overproduction of reactive oxygen species. Agastache rugosa Kuntze, known as Korean mint, possesses a wide spectrum of biological properties including antioxidation, anti-inflammation, and anti-atherosclerosis. Previous studies have reported that A. rugosa protected human keratinocytes against UVB irradiation by restoring the anti-oxidant defense system. However, the anti-photoaging effect of A. rugosa extract (ARE) in animal models has not yet been evaluated. ARE was orally administered to hairless mice at doses of 100 or 250 mg/kg/day along with UVB exposure for 12 weeks. ARE histologically improved UVB-induced wrinkle formation, epidermal thickening, erythema, and hyperpigmentation. In addition, ARE recovered skin moisture by improving skin hydration and transepidermal water loss (TEWL). Along with this, ARE increased hyaluronic acid levels by upregulating HA synthase genes. ARE markedly increased the density of collagen and the amounts of hydroxypoline via two pathways. First, ARE significantly downregulated the mRNA expression of matrix metalloproteinases responsible for collagen degradation by inactivating the mitogen-activated protein kinase/activator protein 1 pathway. Second, ARE stimulated the transforming growth factor beta/Smad signaling, consequently raising the mRNA levels of collagen-related genes. In addition, ARE not only increased the mRNA expression of antioxidant enzymes but also decreased inflammatory cytokines by blocking the protein expression of nuclear factor kappa B. Collectively, our findings suggest that A. rugosa may be a potential preventive and therapeutic agent for photoaging.


Assuntos
Agastache/química , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Envelhecimento da Pele/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Raios Ultravioleta/efeitos adversos , Animais , Antioxidantes/metabolismo , Colágeno/biossíntese , Colágeno/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Camundongos Pelados , Proteínas Quinases Ativadas por Mitógeno/genética , Fosforilação/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Pele/efeitos da radiação , Envelhecimento da Pele/patologia , Envelhecimento da Pele/efeitos da radiação , Proteínas Smad/genética , Proteínas Smad/metabolismo , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Fator de Crescimento Transformador beta/genética
12.
Int J Mol Sci ; 20(18)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514281

RESUMO

The glycerol fermentation of probiotic Staphylococcus epidermidis (S. epidermidis) in the skin microbiome produced butyric acid in vitro at concentrations in the millimolar range. The exposure of dorsal skin of mice to ultraviolet B (UVB) light provoked a significant increased production of pro-inflammatory interleukin (IL)-6 cytokine. Topical application of butyric acid alone or S. epidermidis with glycerol remarkably ameliorated the UVB-induced IL-6 production. In vivo knockdown of short-chain fatty acid receptor 2 (FFAR2) in mouse skin considerably blocked the probiotic effect of S. epidermidis on suppression of UVB-induced IL-6 production. These results demonstrate that butyric acid in the metabolites of fermenting skin probiotic bacteria mediates FFAR2 to modulate the production of pro-inflammatory cytokines induced by UVB.


Assuntos
Ácido Butírico/farmacologia , Interleucina-6/metabolismo , Microbiota/efeitos dos fármacos , Probióticos/farmacologia , Receptores Acoplados a Proteínas-G/metabolismo , Pele/microbiologia , Staphylococcus epidermidis/química , Raios Ultravioleta , Acetolactato Sintase/metabolismo , Animais , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/efeitos da radiação , Ácidos Graxos Voláteis/metabolismo , Feminino , Fermentação , Glicerol/farmacologia , Inflamação/patologia , Camundongos Endogâmicos ICR , Microbiota/efeitos da radiação , Pele/efeitos dos fármacos , Pele/patologia , Pele/efeitos da radiação
13.
Anticancer Res ; 39(9): 5179-5184, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519631

RESUMO

BACKGROUND/AIM: The pesticide dimethoate (O-dimethyl-S- Nmethylcarbamoylmethyl phosphorodithioate) is able to induce severe acute toxicity in living organisms. The aim of this study was to evaluate the effects of ultraviolet radiation, alone or combined with exposure to dimethoate, on the rat skin. MATERIALS AND METHODS: A total of 38 Wistar female rats (Rattus norvegicus albinus), were distributed into four groups: A (n=9) control group, B (n=10) exposed to ultraviolet-B radiation (UV-B), C (n=10) exposed to UV-B followed by application of dimethoate (UV-B+AGRO) and group D (n=9) exposed to dimethoate (AGRO). Histological examination of the tissues, as well as immunohistochemistry for cleaved caspase 3, Ki-67 and COX-2 expression were performed to all groups. RESULTS: Animals submitted to UV-B exhibited hyperkeratosis with moderate cell atypia. Regarding exposure to UV-B+AGRO, the animals presented hyperkeratosis and atrophy, whereas in animals exposed to AGRO, only atrophy was noticed. The immunohistochemical results on skin revealed that UVB, AGRO and UVB+AGRO decreased cleaved caspase 3 and Ki-67 expression when compared to the control group (p<0.05). COX-2 expression decreased to UVB or AGRO groups compared to controls (p<0.05). CONCLUSION: UV-B or AGRO exposure is able to induce histopathological changes and altered expression of cleaved caspase-3 and Ki-67 in rat skin, thus being categorized as a risk condition for skin carcinogenesis.


Assuntos
Dimetoato/farmacologia , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Raios Ultravioleta , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Biomarcadores , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Feminino , Imuno-Histoquímica , Ratos , Ratos Wistar , Pele/metabolismo
14.
Radiat Res ; 192(4): 410-421, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31390312

RESUMO

Radiation-induced acute skin injury and consequent fibrosis are common complications of cancer radiotherapy and radiation accidents. Stromal cell-derived factor-1α (SDF-1α) and its receptor, CXC chemokine receptor 4 (CXCR4) have been shown to be involved in multiple cellular events. However, the role of SDF-1α/CXCR4 axis in radiation-induced acute injury and fibrosis of skin has not been reported. In this study, we found that the expression of SDF-1α and CXCR4 was significantly increased in irradiated skin tissues of humans, monkeys and rats, compared to their nonirradiated counterparts. Mice with keratinocyte-specific ablation of CXCR4 showed less severe skin damage than wild-type mice after receiving a 35 Gy dose of radiation. Consistently, subcutaneous injection of AMD3100, an FDA approved SDF-1α/CXCR4 inhibitor, attenuated skin injury and fibrosis induced by exposure to radiation in a rat model. Mechanically, the SDF-1α/CXCR4 axis promotes pro-fibrotic TGF-b/Smad signaling through the PI3K-MAPK signaling cascade in human keratinocyte HaCaT cells and skin fibroblast WS1 cells. AMD3100 inhibited Smad2 nuclear translocation and transcriptional activity of Smad2/3 induced by radiation, which suppressed the pro-fibrotic TGF-b/Smad signaling pathway activated by exposure. Taken together, these findings demonstrate the involvement of SDF-1α/CXCR4 axis in radiation-induced acute injury and fibrosis of skin, and indicate that AMD3100 would be an effective countermeasure against these diseases.


Assuntos
Quimiocina CXCL12/metabolismo , Lesões por Radiação/metabolismo , Receptores CXCR4/metabolismo , Pele/patologia , Pele/efeitos da radiação , Animais , Fibrose , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Técnicas de Inativação de Genes , Compostos Heterocíclicos/farmacologia , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos da radiação , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Lesões por Radiação/patologia , Ratos , Receptores CXCR4/deficiência , Receptores CXCR4/genética , Pele/lesões , Pele/metabolismo , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta/metabolismo
15.
PLoS One ; 14(8): e0220030, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31390347

RESUMO

It is estimated that approximately 24% of the US population has at least one tattoo. However, tattoo ink ingredients include heavy metals (high atomic number Z) that are not regulated, which can cause skin reactions. This study investigates the dosimetric effects in surface dose due to high-Z elements in tattoo ink under electron beam irradiation. Four commercially available tattoo ink colors, black, red, yellow, and blue were chosen. The elemental composition of the tattoo ink samples was analyzed using X-ray Fluorescence (XRF). An ultrathin-window parallel plate ion chamber was used to measure the surface dose perturbation (ratio of ionizations with and without tattoo ink) for 6 - 20 MeV electron beams. The elemental concentration in the tattoo ink samples showed high-Z elements, with Z ranging from 11 to 92. The dose perturbation ranged from 1.4% up to 6% for the yellow ink for the 6 MeV electron beam, with similar values across the rest of the electron energies, whereas the black, red, and blue inks presented up to 3% dose perturbation for the same range of energies. Based on this initial study, we conclude that commercially available tattoo inks contain large amounts of high-Z metals that may contribute to dose perturbation. Therefore treatment of superficial lesions with electron beams in a tattooed area should be monitored for signs of early skin reaction during radiation therapy treatments.


Assuntos
Radioterapia/efeitos adversos , Tatuagem , Tinta , Radiometria , Pele/metabolismo , Pele/efeitos da radiação
16.
J Photochem Photobiol B ; 198: 111565, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31374350

RESUMO

The incidence of skin cancers has increased worldwide, requiring more prevention of this type of cancer. The use of sunscreen and the control of the time of exposure to sunlight are the recognized forms of prevention. However, new substances have been researched in order to develop formulations with more efficient protective activity. Citral is a natural compound with lemon scent that is used in food and cosmetic industries. The present work evaluated the chemoprotective effect of citral during UVB-induced skin carcinogenesis. Male hairless mice HRS/J, 8-12 weeks old, were exposed to UVB irradiation for 24 weeks, with a cumulative radiation dose of 13.875 J/cm2. Citral (0.1, 0.5 and 1%) was applied to the skin at a dosage of 0.1 g/animal, 5 min after UVB exposure. At the end of the experiment, the number of lesion/animal, and size of lesions were measured. The histological sections of the skin were evaluated for the presence and intensity of actinic keratosis and squamous cell carcinoma. TUNEL assay was performed for apoptosis evaluation. Skin samples were used for the measurement of oxidative stress parameters (total radical-trapping antioxidant parameter of skin, glutathione, catalase activity and malondialdehyde), and cytokines levels (IL-1ß, IL-4, IL-10, IL-23, TNF-α, and IFNγ). Citral 1% completely inhibited UVB-induced skin carcinogenesis by reducing levels of oxidative stress and pro-inflammatory cytokines, increasing apoptotic rate in the skin.


Assuntos
Carcinoma de Células Escamosas/patologia , Monoterpenos/farmacologia , Neoplasias Cutâneas/patologia , Pele/efeitos dos fármacos , Raios Ultravioleta , Animais , Antioxidantes/metabolismo , Carcinoma de Células Escamosas/prevenção & controle , Catalase/metabolismo , Citocinas/metabolismo , Glutationa/metabolismo , Ceratose/patologia , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Pelados , Monoterpenos/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Pele/metabolismo , Pele/efeitos da radiação , Neoplasias Cutâneas/prevenção & controle
17.
Mar Drugs ; 17(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374828

RESUMO

Excessive exposure to ultraviolet (UV) radiation is the main risk factor to develop skin pathologies or cancer because it encourages oxidative condition and skin inflammation. In this sense, strategies for its prevention are currently being evaluated. Natural products such as carotenoids or polyphenols, which are abundant in the marine environment, have been used in the prevention of oxidative stress due to their demonstrated antioxidant activities. Nevertheless, the anti-inflammatory activity and its implication in photo-prevention have not been extensively studied. Thus, we aimed to evaluate the combination of fucoxanthin (FX) and rosmarinic acid (RA) on cell viability, apoptosis induction, inflammasome regulation, and anti-oxidative response activation in UVB-irradiated HaCaT keratinocytes. We demonstrated for the first time that the combination of FX and RA (5 µM RA plus 5 µM FX, designated as M2) improved antioxidant and anti-inflammatory profiles in comparison to compounds assayed individually, by reducing UVB-induced apoptosis and the consequent ROS production. Furthermore, the M2 combination modulated the inflammatory response through down-regulation of inflammasome components such as NLRP3, ASC, and Caspase-1, and the interleukin (IL)-1ß production. In addition, Nrf2 and HO-1 antioxidant genes expression increased in UVB-exposed HaCaT cells pre-treated with M2. These results suggest that this combination of natural products exerts photo-protective effects by down-regulating NRLP3-inflammasome and increasing Nrf2 signalling pathway.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cinamatos/farmacologia , Depsídeos/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Xantofilas/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Sinergismo Farmacológico , Humanos , Inflamassomos/efeitos dos fármacos , Inflamassomos/imunologia , Inflamassomos/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Queratinócitos/efeitos da radiação , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Transdução de Sinais/efeitos da radiação , Pele/citologia , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Envelhecimento da Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos
18.
Int J Dermatol ; 58(10): 1148-1152, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31418463

RESUMO

BACKGROUND: Several studies have suggested that the lower vitamin D levels in blacks is attributable to the effect of increased pigmentation in blocking cutaneous ultraviolet (UV)-mediated production of vitamin D. Albinos are devoid of melanin and should invariably have higher vitamin D levels when compared with their pigmented counterparts. However, strict photoprotection required in their medical management has been shown to reduce UV-dependent vitamin D production. Associations between low vitamin D and several diseases suggest that the pattern of vitamin D in the black African albino be investigated. OBJECTIVE: To compare the vitamin D levels between albinos and normal pigmented controls in Anambra State, Nigeria, and thus highlight the impact of skin pigmentation and sun protection practices on vitamin D levels. METHODOLOGY: This was a cross-sectional study of a consecutive series of albinos from the Albino Foundation, Anambra State. The vitamin D levels of 61 albinos and 58 matched pigmented controls were analyzed. The sun exposures of the participants were calculated using validated sun exposure questionnaires. RESULTS: The albinos had significantly higher vitamin D levels (median 95.9 [50.1-177.4] ng/ml) than the controls (78.2 [12.1-250] ng/ml). None of the albinos had low vitamin D levels. None of the sun protection practices had significant effects on vitamin D levels. CONCLUSION: This study contests the claim that black Africans including albinos have low vitamin D levels. Albinos living in South East Nigeria have significantly higher vitamin D levels than their pigmented counterparts.


Assuntos
Albinismo/sangue , Pigmentação da Pele , Pele/metabolismo , Vitamina D/sangue , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Nigéria , Roupa de Proteção , Pele/efeitos da radiação , Luz Solar/efeitos adversos , Protetores Solares/administração & dosagem , Clima Tropical , Vitamina D/metabolismo , Adulto Jovem
19.
Radiat Res ; 192(5): 473-482, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31415221

RESUMO

Radiation therapy is a mainstream strategy in the treatment of several cancer types that are surgically unresectable. Unfortunately, cancer patients often suffer from unintended consequences of radiotherapy, including the development of skin inflammation (dermatitis), which may progress to fibrosis. These morbid complications often require interruption of radiotherapy and threaten the relapse of underlying cancer. Current treatment options for radiation dermatitis are suboptimal and compel the need to develop safer, more effective therapies. In this study, we assessed the biophysical properties of topically-formulated esomeprazole (here referred to as dermaprazole) and performed proof-of-concept studies to evaluate its efficacy in vitro and in vivo. We found that dermaprazole induced nuclear translocation of erythroid 2-related factor 2 (Nrf2) and significantly upregulated heme oxygenase 1 (HO1) gene and protein expression in a 3D human skin model. Our animal study demonstrated that dermaprazole improved macroscopic appearance of the irradiated skin and accelerated healing of the wounds. Histopathology data corroborated the photographic evidence and confirmed that both prophylactically and therapeutically administered dermaprazole conferred potent anti-inflammatory and antifibrotic effects. Gene expression data showed that dermaprazole downregulated several pro-oxidant, pro-inflammatory and profibrotic genes. In conclusion, topical formulation of the FDA-approved drug esomeprazole is highly effective in attenuating dermal inflammation and fibrosis.


Assuntos
Administração Tópica , Esomeprazol/administração & dosagem , Fibrose/tratamento farmacológico , Inflamação/tratamento farmacológico , Radiodermatite/tratamento farmacológico , Transporte Ativo do Núcleo Celular , Animais , Anti-Inflamatórios/administração & dosagem , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Heme Oxigenase-1/metabolismo , Humanos , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Modelos Anatômicos , Fator 2 Relacionado a NF-E2/metabolismo , Radioterapia/efeitos adversos , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/efeitos da radiação , Cicatrização/efeitos dos fármacos
20.
Med Phys ; 46(10): 4654-4665, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31407346

RESUMO

PURPOSE: Radiation doses accumulated during very complicated image-guided x-ray procedures have the potential to cause stochastic, but also deterministic effects, such as skin rashes or even hair loss. To monitor and reduce radiation-related risks to patients' skin, x-ray imaging devices are equipped with online air kerma monitoring components. Traditionally, such measurements have been used to estimate skin entrance dose by (a) estimating air kerma at the interventional reference point (IRP), (b) forward projecting the dose distribution, and (c) considering a backscatter factor among other correction factors. Unfortunately, the complicated interaction between incident x-ray photons, secondary electrons, and skin tissue cannot be properly accounted for by assuming a linear relationship between forward projected air kerma and a backscatter factor. Gold standard skin dose models are therefore determined using Monte Carlo (MC) techniques. However, MC simulations are computationally complex in general and possible acceleration mainly depends on the employed hardware and variance reduction techniques. To obtain reliable and fast dose estimates, we propose to combine MC-based simulations with learning-based methods. METHODS: The basic idea of our method is to approximate the radiation physics to calculate a first-order exposure estimate quickly. This initial estimate is then refined using prior knowledge derived from MC simulations. To this end, the primary photon propagation inside a voxelized patient model is estimated using a less accurate but fast photon ray casting (RC) simulation based on the Beer-Lambert law. The results of the RC simulation are then fed into a convolutional neural network (CNN), which maps the propagation of primary photons to the dose deposition inside the patient model. Additionally, the patient model itself including anatomy and material properties, such as mass density and mass energy-absorption coefficients, are fed into the CNN as well. The CNN is trained using smoothed results of MC simulations as output and RC simulations of identical imaging settings and patient models as input. RESULTS: In total, 163 MC and associated RC simulations are carried out for the head, thorax, abdomen, and pelvis in three different voxel phantoms. We used 10 8 or 10 9 primarily emitted photons sampled from a 125 kV peak voltage spectrum, respectively. Edge-preserving smoothing (EPS) is applied to reduce (a) general stochastic uncertainties and (b) stochastic uncertainty concerning MC simulations of less primary photons. The CNN is trained using seven imaging settings of the abdomen in a single phantom. Testing its performance on the remaining datasets, the CNN is capable of estimating skin dose with an error of below 10% for the majority of test cases. CONCLUSION: The combination of deep neural networks and MC simulation of particle physics has the potential to decrease the computational complexity of accurate skin dose estimation. The proposed approach can provide dose distributions in under one second when running on high-end hardware. On lower cost hardware, it took up to 2 min to arrive at the same result. This makes our approach applicable in high-end environments as well as in budget solutions. Furthermore, the number of primary photons only affects the training time, while the execution time is independent of the number of primary photons.


Assuntos
Fluoroscopia/métodos , Aprendizado de Máquina , Método de Monte Carlo , Doses de Radiação , Pele/diagnóstico por imagem , Pele/efeitos da radiação , Incerteza
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