RESUMO
INTRODUCTION: Xeroderma pigmentosum (XP) is a rare intractable disease without a fundamental treatment, presenting with severe photosensitivity, freckle-like pigmented and depigmented maculae and numerous skin cancers before the age of 10 years without strict sun protection. About 70% of the patients exhibit extremely severe sunburn reactions and most of them develop neurological symptoms, including sensorineural hearing impairment and progressive peripheral and central nervous disorders beginning from childhood ages. In the preclinical study, we found that N-acetyl-5-methoxytryptamine was effective in suppressing skin tumour development in addition to improvement of auditory brainstem response in chronically ultraviolet-irradiated XP-A model mice. METHODS AND ANALYSIS: On the bases of the preclinical study, we conduct a clinical trial on the efficacy of NPC-15 for patients with XP with exaggerated sunburn reaction type by a multicentre, double-blinded placebo-controlled, two-group crossover study followed by a 52 weeks open study. ETHICS AND DISSEMINATION: Ethics approval is overseen by the Kobe University Institutional Review Board and Osaka Medical and Pharmaceutical University Institutional Review Board, and the study is conducted in accordance with the approved protocol. All participants will be required to provide written informed consent. Findings will be disseminated through scientific and professional conferences and peer-reviewed journal publications. The data sets generated during the study will be available from the corresponding author on reasonable request. TRIAL REGISTRATION NUMBER: jRCTs051210181.
Assuntos
Neoplasias Cutâneas , Queimadura Solar , Xeroderma Pigmentoso , Animais , Camundongos , Xeroderma Pigmentoso/complicações , Queimadura Solar/complicações , Queimadura Solar/prevenção & controle , Estudos Cross-Over , Japão , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
Life on earth has constantly coped with the impact of solar radiation, especially solar ultraviolet radiation (solar UV). Various biological mechanisms protect us from solar UV. New devices emitting shorter wavelengths UV-C, i.e. <254 nm emitted by conventional UV germicidal lamps, have emerged. These shorter wavelength UV-C emitting devices are useful for various purposes, including microorganism inactivation. However, as solar UV-C does not reach the earth surface, biological impacts of UV-C has been studied using 254 nm germicidal lamps, and those using shorter wavelength UV-C is rarely known. To balance the utility and risk of UV-C, the biological effect of these new UV-C emitting devices must be investigated. In addition, our knowledge of biological impacts of the wavelength-dependent entire UV (100-400 nm) must be enhanced. In this review, we briefly summarize the biological impacts of shorter wavelength UV-C. Mechanisms of UV-C-induced cellular damage and factors affecting the microorganism inactivation efficiency of UV-C have been discussed. In addition, we theoretically estimate the probable photocarcinogenic action spectrum of shorter wavelength UV-C. We propose that increasing the knowledge on UV-C will facilitate the adoption of shorter wavelength UV-C emitting new devices in an optimal and appropriate manner.
Assuntos
Energia Solar , Raios Ultravioleta , Luz SolarRESUMO
INTRODUCTION: Surgical site infection is one of the most severe complications of surgical treatments. However, the optimal procedure to prevent such infections remains uninvestigated. Ultraviolet radiation C (UVC) with a short wavelength has a high bactericidal effect; however, it is cytotoxic. Nonetheless, given that UVC with a wavelength of 222 nm reaches only the stratum corneum, it does not affect the skin cells. This study aimed to investigate the safety of 222-nm UVC irradiation and to examine its skin sterilization effect in healthy volunteers. METHODS: This trial was conducted on 20 healthy volunteers. The back of the subject was irradiated with 222-nm UVC at 50-500 mJ/cm2, and the induced erythema (redness of skin) was evaluated. Subsequently, the back was irradiated with a maximum amount of UVC not causing erythema, and the skin swabs before and after the irradiation were cultured. The number of colonies formed after 24 hours was measured. In addition, cyclobutene pyrimidine dimer (CPD) as an indicator of DNA damage was measured using skin tissues of the nonirradiated and irradiated regions. RESULTS: All subjects experienced no erythema at all doses. The back of the subject was irradiated at 500 mJ/cm2, and the number of bacterial colonies in the skin swab culture was significantly decreased by 222-nm UVC irradiation. The CPD amount produced in the irradiated region was slightly but significantly higher than that of the non-irradiated region. CONCLUSION: A 222-nm UVC at 500 mJ/cm2 was a safe irradiation dose and possessed bactericidal effects. In the future, 222-nm UVC irradiation is expected to contribute to the prevention of perioperative infection.
Assuntos
Dano ao DNA/efeitos da radiação , Microbiota/efeitos da radiação , Pele/efeitos da radiação , Esterilização/métodos , Raios Ultravioleta/efeitos adversos , Adulto , Dorso , Biópsia , Contagem de Colônia Microbiana , Eritema/diagnóstico , Eritema/etiologia , Voluntários Saudáveis , Humanos , Masculino , Dímeros de Pirimidina/análise , Dímeros de Pirimidina/efeitos da radiação , Pele/microbiologia , Infecção da Ferida Cirúrgica/microbiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Resultado do TratamentoRESUMO
Germicidal lamps that emit primarily 254 nm ultraviolet radiation (UV) are routinely utilized for surface sterilization but cannot be used for human skin because they cause genotoxicity. As an alternative, 222-nm UVC has been reported to exert sterilizing ability comparable to that of 254-nm UVC without producing cyclobutane pyrimidine dimers (CPDs), the major DNA lesions caused by UV. However, there has been no clear evidence for safety in chronic exposure to skin, particularly with respect to carcinogenesis. We therefore investigated the long-term effects of 222-nm UVC on skin using a highly photocarcinogenic phenotype mice that lack xeroderma pigmentosum complementation group A (Xpa-) gene, which is involved in repairing of CPDs. CPDs formation was recognized only uppermost layer of epidermis even with high dose of 222-nm UVC exposure. No tumors were observed in Xpa-knockout mice and wild-type mice by repetitive irradiation with 222-nm UVC, using a protocol which had shown to produce tumor in Xpa-knockout mice irradiated with broad-band UVB. Furthermore, erythema and ear swelling were not observed in both genotype mice following 222-nm UVC exposure. Our data suggest that 222-nm UVC lamps can be safely used for sterilizing human skin as far as the perspective of skin cancer development.
Assuntos
Neoplasias Induzidas por Radiação/etiologia , Neoplasias Cutâneas/etiologia , Esterilização/instrumentação , Raios Ultravioleta , Animais , Ensaio de Imunoadsorção Enzimática , Camundongos , Camundongos Pelados , Camundongos Knockout , Neoplasias Induzidas por Radiação/genética , Neoplasias Cutâneas/genética , Proteína de Xeroderma Pigmentoso Grupo A/genéticaRESUMO
Fibroblastic connective tissue nevus (FCTN) is a benign cutaneous mesenchymal lesion characterized by proliferation of CD34-positive fibroblastic/myofibroblastic spindle-shaped cells. We report a case of agminated FCTN on the right lower abdomen of a 1-year-old boy.
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Fibroblastos/patologia , Nevo/patologia , Neoplasias Cutâneas/patologia , Abdome , Humanos , Lactente , MasculinoRESUMO
Voriconazole is an antifungal agent and used as a prophylactic measure, especially in immunocompromised patients. However, there have been several reports of its adverse reactions, namely photosensitivity with intense inflammatory rashes and subsequent skin cancer development. To assess the effects of photosensitizing drugs voriconazole and hydrochlorothiazide (HCTZ) on the enhancement of UV-induced inflammatory responses and UV-induced tumorigenesis, we utilized Xpa-knockout mice, which is DNA repair-deficient and more susceptible to UV-induced inflammation and tumor development than wild-type mice. Administration of voriconazole prior to broadband UVB exposure significantly upregulated multiple inflammatory cytokines compared with the vehicle- or HCTZ-administered groups. Voriconazole administration along with chronic UVB exposure produced significantly higher number of skin tumors than HCTZ or vehicle in Xpa-knockout mice. Furthermore, the investigation of UVB-induced DNA damage using embryonic fibroblasts of Xpa-knockout mice revealed a significantly higher 8-oxo-7,8-dihydroguanine level in cells treated with voriconazole N-oxide, a voriconazole-metabolite during UV exposure. The data suggest that voriconazole plus UVB-induced inflammatory response may be related to voriconazole-induced skin phototumorigenesis.
Assuntos
Hidroclorotiazida/efeitos adversos , Inflamação/induzido quimicamente , Neoplasias Induzidas por Radiação/patologia , Transtornos de Fotossensibilidade/induzido quimicamente , Neoplasias Cutâneas/etiologia , Raios Ultravioleta , Voriconazol/efeitos adversos , Proteína de Xeroderma Pigmentoso Grupo A/genética , Animais , Antifúngicos/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Cocarcinogênese , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Knockout , Neoplasias Cutâneas/genéticaRESUMO
Fatty acid binding proteins (FABPs) are capable of binding long-chain FA and are involved in intracellular FA transport and signal transduction. In sebaceous glands, FABP5 is highly expressed in differentiated sebocytes; though, its function remains unclear. In this study, we examined the role of FABP5 in sebocytes using FABP5-deficient mice. The size of sebaceous glands was significantly reduced, while the sebum volume was increased with altered lipid composition in FABP5-deficient mice. However, no significant differences were discerned in the expression of proliferation or differentiation markers including Blimp1, c-myc, Ki67 and peroxisome proliferator-activated receptors (PPAR)γ between wild-type and FABP5-deficient sebaceous glands. The expression of cellular retinoic acid binding protein-2 (CRABP2) that is a competitor of FABP5 for RA signalling was increased in FABP5-deficient mice. These results suggest that FABP5 is involved in the regulation of sebaceous gland activity through modulation of cellular lipid signalling and/or metabolism in the sebocytes.