RESUMO
BACKGROUND: Overexposure to sunlight can have many harmful biological effects on the skin, leading to skin cancer and photoaging. As ultraviolet (UV) radiation has been identified as a cause of DNA damage and oxidative stress in the skin, the photoprotection provided by sunscreens is evaluated through their ability to filter UV light, using the sun protection factor (SPF). However, recent data have shown that high-energy visible (HEV) light can also cause biological skin damage. OBJECTIVES: To develop a new in vivo method for evaluating the protection provided by sunscreens across a broad range of wavelengths, including the HEV band, based on multispectral image analysis. METHODS: This study evaluated the absorption properties of six commercially available sunscreens (five SPF 50+ products containing organic UV filters, and one product containing the wide spectrum filter, phenylene bis-diphenyltriazine [TriAsorB™]) and of a control product containing no filter. Multispectral images were acquired from the skin on the forearms of healthy volunteers, before and after application of the test products. Images taken with LEDs emitting light at wavelengths ranging from UV to infrared were used to generate light reflectance maps for each product. The levels of absorbance of light in the UV and visible bands were then calculated. RESULTS: The product containing the wide spectrum filter exhibited significantly higher absorbance over the HEV band (380-450 nm) than the control product and the other commercial sunscreens. All the sunscreens tested showed the same level of absorbance at 365 nm (UVA). CONCLUSIONS: Multispectral imaging provides a simple and reliable in vivo method for assessing the real-world protection provided by sunscreens against all forms of photo-induced skin damage, including that induced by HEV radiation.
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Neoplasias Cutâneas , Protetores Solares , Humanos , Luz , Raios Ultravioleta , PeleRESUMO
Accumulating evidence from numerous comprehensive studies has demonstrated that blue light, in particular high-energy visible light, can exert a range of harmful effects on skin cells. These forms of radiation are now known to be able to trigger oxidation reactions, DNA damage, erythema and pigmentary changes, and may also be associated with photoaging. Sunscreens protecting the skin from only ultraviolet (UV)-B and UVA rays can therefore no longer be regarded as sufficient to help prevent skin damage from sunlight, and products containing filters that can provide broad-spectrum photoprotection are required. To meet this need, a new sunscreen formulation that provides photoprotection against solar radiation with wavelengths ranging from UV to visible light has been developed, using an innovative organic sun filter with unique optical properties: phenylene bis diphenyltriazine (TriAsorB™). This article outlines the development and characteristics of this innovative filter and describes new key results from studies performed to assess the effectiveness and safety of the filter and the new sunscreen product. The studies conducted so far demonstrate that the filter has a good human and environmental safety profile. In addition, the sunscreen, which contains TriAsorB in combination with three other UV filters to offer broad-spectrum sun protection with a high sun protection factor (SPF50+ ), appears to effectively prevent multiple forms of cellular photodamage, in particular blue light-induced oxidatively generated DNA lesions. Overall, the available data indicate that regular use of the TriAsorB-containing sunscreen could help prevent solar radiation-induced skin damage and the development of signs of premature skin aging, as well as photodermatoses caused or exacerbated by visible light.
Assuntos
Envelhecimento da Pele , Protetores Solares , Humanos , Pele , Fator de Proteção Solar , Luz Solar/efeitos adversos , Protetores Solares/farmacologia , Raios Ultravioleta/efeitos adversosRESUMO
Sunlight induces actinic keratosis, skin cancers and photoaging. Photoprotection is thus a major issue in public health to prevent the harmful effects of solar ultraviolet (UV) radiations. Recent data have shown that the visible (VIS) and infrared (IR) radiations can lead to skin damage by oxidative stress, suggesting that a balanced protection across the entire spectrum of sunlight is necessary to prevent cutaneous alterations. In this context, we developed a new generation of sunfilter called Phenylene Bis-Diphenyltriazine or TriAsorB (CAS N°55514-22-2). The aim of the present study was to assess the photoprotective efficacy of TriAsorB from UV to IR light. Spectrophotometric assays were performed to measure absorption and reflectance of TriAsorB in the different spectral ranges of sunlight: UV, VIS including blue light or high energy visible (HEV) and IR. DNA damage was evaluated using reconstructed human epidermis (RHE): 8-hydroxy-2'-deoxyguanosine (8OHdG) in response to HEV exposure, pyrimidine dimers (CPDs) and (6-4) photoproducts following solar-simulated radiation (SSR). TriAsorB is a broad spectrum UVB + UVA filter including long UVA. Interestingly, it also absorbs VIS radiations, especially in the HEV region. These radiations are also reflected. Protection in the IR spectral range is weak. Furthermore, the sunfilter specifically protects the skin against the oxidative lesions 8OHdG induced by HEV and prevents SSR-induced DNA damage. Thus, TriAsorB is an innovative sunfilter that might be used in sun care products for skin photoprotection from UV to VIS radiations. Finally, it prevents sunlight genotoxicity and protected the skin against solar radiations, especially blue light.
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Protetores Solares , Raios Ultravioleta , Humanos , Dímeros de Pirimidina , Pele , Luz Solar , Protetores Solares/farmacologia , Raios Ultravioleta/efeitos adversosRESUMO
The hydrotherapy centre in Avène, France, is used extensively to treat inflammatory skin diseases. Nevertheless, the immune mechanisms targeted by Avène Thermal Spring Water (TSW) are not fully understood. Here, we review the main results reported regarding the effects of Avène TSW on the immune system. In particular, mast cells, dendritic cells (DCs) and CD4+ T cells have been shown to be modulated by Avène TSW. All in all, the studies carried out on the effects of Avène TSW on leucocytes indicate that this water is endowed with a tolerogenic potential.
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Células Dendríticas , Hidroterapia , Mastócitos , Águas Minerais , França , Fontes TermaisRESUMO
BACKGROUND: Chronic hand eczema (CHE) is the most common skin disorder affecting the hands. It causes major physical and psychological burden for patients. Classification of CHE remains challenging because of its aetiological and clinical heterogeneity. OBJECTIVES: Using latent class analysis (LCA) on a large categorical data set, our aim was to identify distinct phenotypes in a cohort of unselected CHE patients based upon clinical, genetic, molecular and physical parameters of the affected skin. METHODS: We performed two independent LCA on a cohort of 71 well-characterized patients that initially integrated clinical severity, total immunoglobulin E plasma level, transepidermal water loss, hydration index, interleukin(IL)-8 lesional skin level, Staphylococcus (aureus and epidermidis) colonization, FLG genotype and the expression (mRNA) of genes involved either in the filaggrin degradation and the natural moisturizing factor synthesis, the cornified envelope formation, the tight junctions' structure and the desquamation process, or encoding antimicrobial peptides and chemokines. RESULTS: The first LCA categorized patients into a group displaying high severity of CHE, high skin barrier impairment, high Staphylococcus colonization, high IL-8 skin level and high frequency of mutation in the FLG gene and a second group with opposite characteristics. The second LCA identified two independent groups of patients categorized by their low or high level of skin barrier impairment and corresponding changes in the expression of the related genes. CONCLUSIONS: Our study suggests that the degree of skin barrier dysfunction is the most important parameter to discriminate CHE patients and probably plays a pivotal role in the pathogenesis of the disease whatever the aetiological factors. As far as we know, this is the first study to address this topic using a statistical categorization method without preconception.
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Eczema , Epiderme , Eczema/genética , Proteínas Filagrinas , Humanos , Proteínas de Filamentos Intermediários/genética , Análise de Classes Latentes , Pele , Staphylococcus aureusRESUMO
Atopic dermatitis (AD) is an inflammatory and pruritic dermatosis of multifactorial origin. Topical steroids are the first line treatment for severe AD however alternatives treatment are increasingly needed. A biological concentrate was elaborated from culture of an Avène aquatic microflora isolate namely Aquaphilus dolomiae. Numerous extracts were evaluated in relevant AD in vitro models with human keratinocytes. Among these extracts, a particular one I-modulia® was found to be remarkable in terms of pharmacological activities: innate immunity modulating by agonizing Toll like receptor (TLR)2, TLR4 and TLR5, induction of anti-microbial peptides, inhibition of cytokines characteristics of T helper (Th)1, Th2 and Th17 responses, inhibition of Protease-activated-receptor (PAR) 2 and Thymic-stromal-lymphopoeitin (TSLP) both being known to be upregulated in pruritus. Additionally, when human dendritic cells (DC) were stimulated in vitro by Staphylococcus aureus secretomes from AD children lesions, I-modulia® was capable to induce IL-10 secretion to activate regular T lymphocytes and rendered DC tolerogenic. I-modulia®, extract of biotech origin incorporated in emollient, displays anti-inflammatory, anti-pruritus activities, restores homeostasis immune and ameliorates AD in young infant.
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Anti-Inflamatórios/farmacologia , Antipruriginosos/farmacologia , Dermatite Atópica/tratamento farmacológico , Fatores Imunológicos/farmacologia , Neisseriaceae/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/metabolismo , Antipruriginosos/isolamento & purificação , Antipruriginosos/uso terapêutico , Citocinas/antagonistas & inibidores , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/microbiologia , Avaliação Pré-Clínica de Medicamentos , Disbiose/tratamento farmacológico , Humanos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/uso terapêutico , Queratinócitos/efeitos dos fármacos , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/imunologia , Receptores Toll-Like/agonistasRESUMO
Sunscreens must now be effective in protecting skin from ultraviolet, as well as visible/infrared radiation. Here, TriAsorB, a new broad-spectrum sun filter, was formulated with three other sunscreens and their distribution on human skin was studied using a standard penetration protocol and two novel mass spectrometry imaging techniques: atmospheric pressure matrix assisted laser desorption ionization (AP-MALDI) coupled to high resolution mass spectrometry and time of flight - secondary ion mass spectrometry (ToF-SIMS). The standard penetration protocol showed that sun filters absorption was very low, with most of the dose recovered at the surface (none entered the receptor fluid). Absorption was not increased in damaged skin. The results were confirmed by AP-MALDI and ToF-SIMS imaging of the spatial distribution of molecular species in cross-section samples of human skin. Each sun filter was detected on or in the stratum corneum, with a good homogenous coverage over the valleys and peaks of the skin, and correlated well with the distribution of endogenous biomarkers. In conclusion, conventional and novel imaging analysis methods showed that the sun filters remained mainly on the skin surface after topical application. Mass spectrometry imaging is a promising complementary approach to traditional skin penetration studies to visualize penetration of compounds.
Assuntos
Pele , Protetores Solares , Epiderme , Humanos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Espectrometria de Massa de Íon Secundário/métodosRESUMO
BACKGROUND: A number of studies argue in favour of an important role of microbial colonization, in particular of Staphylococcus aureus, in triggering atopic dermatitis (AD) flare-up and psoriasis, in particular through the superantigenic properties of toxins generated by S. aureus. OBJECTIVES: The aim of this study was to assess the efficacy of a 3-week Avène hydrotherapy on the skin surface of patients suffering from psoriasis or atopic dermatitis. METHODS: Skin samples were taken from healthy subjects or atopic (n = 18) or psoriatic patients (n = 39) undergoing hydrotherapy at Avène at the beginning (D0) and the end of treatment (D18). The severity of the dermatosis was evaluated according to SCORing Atopic Dermatitis (SCORAD) or Psoriasis Area Severity Index (PASI) scores at D0 and D18. Marker of inflammation interleukin 8 (IL-8), S. aureus colonization (protein A) and enterotoxins were assessed in skin samples using RT-PCR. RESULTS: At D0, significant differences were observed between healthy subjects and atopic or psoriatic patients in all the parameters evaluated (IL-8, protein A). At the end of the hydrotherapy, a significant decrease in SCORAD was associated with a significant reduction of IL-8, S. aureus colonization and enterotoxin D in patients with atopic dermatitis. Similarly, a significant decrease in PASI was associated with a significant reduction of IL-8, S. aureus colonization and enterotoxin N in patients with psoriasis. CONCLUSIONS: This study demonstrates the positive effects of Avène hydrotherapy on the skin of patients suffering from chronic dermatosis, with decreased inflammation and reduced colonization by S. aureus.
Assuntos
Dermatite Atópica/terapia , Hidroterapia , Águas Minerais/uso terapêutico , Psoríase/terapia , Infecções Cutâneas Estafilocócicas/terapia , Adulto , Criança , Pré-Escolar , Dermatite Atópica/metabolismo , Dermatite Atópica/microbiologia , Enterotoxinas/metabolismo , Humanos , Lactente , Interleucina-8/metabolismo , Águas Minerais/administração & dosagem , Águas Minerais/microbiologia , Psoríase/metabolismo , Psoríase/microbiologia , Índice de Gravidade de Doença , Proteína Estafilocócica A/metabolismo , Staphylococcus aureus/crescimento & desenvolvimento , Estatísticas não Paramétricas , Resultado do Tratamento , Adulto JovemRESUMO
Atopic dermatitis (AD) is a multifactorial chronic inflammatory disease mainly stemming from a genetic predisposition that leads to hypersensitivity to environmental factors and a common involvement of Staphylococcus aureus (SA) colonization. The aim of this work was to propose a new non-invasive approach to enumerate the genes coding for the toxins of SA in atopic skin samples. In parallel, the study aimed to evaluate the change in AD through 3 markers of the inflammatory response: IL-8, IL-1RA/IL-1alpha and IL-18. These methods were tested on 31 patients with AD, and finally on a group of 19 subjects for whom clinical improvement had been reported after various treatments. The study revealed the presence of a large number of genes encoding toxins in atopic samples, indicating a high rate of SA colonization, and also an increase in the level of all cytokine markers in atopic skin compared to the skin of healthy subjects. Finally, we found a positive correlation between increases in the SCORAD (Scoring Atopic Dermatitis Index) value after treatment and the corresponding evolution of the SA density. These methods provide a means to clinically evaluate the course of AD, and may help in the development of potential treatments.
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Toxinas Bacterianas/genética , Dermatite Atópica/genética , Reação em Cadeia da Polimerase/métodos , Staphylococcus aureus/genética , Toxinas Bacterianas/isolamento & purificação , Estudos de Casos e Controles , Criança , Pré-Escolar , DNA Bacteriano/isolamento & purificação , Dermatite Atópica/microbiologia , Predisposição Genética para Doença , Genótipo , Humanos , Lactente , Inflamação/genética , Inflamação/microbiologia , Interleucinas/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Índice de Gravidade de Doença , Infecções Cutâneas Estafilocócicas/genética , Infecções Cutâneas Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Resultado do TratamentoRESUMO
Phospholipases A2 are enzymes that catalyze the release of fatty acids from the sn-2 position of phospholipids. Fatty acids have been suggested to play a key role in the barrier function of the epidermis. The aim of this study was to identify and characterize the type of secretory phospholipase A2 expressed in human epidermis. We report the molecular cloning of two secretory phospholipase A2 in the human epidermis. The first enzyme is identical to human pancreatic type IB phospholipase A2. Western blots revealed a 14 kDa protein localized in the soluble fraction. The second phospholipase A2 is identical to human synovial type IIA enzyme and is localized in the membrane fraction. By semiquantitative reverse transcription-polymerase chain reaction performed on horizontal sections of the epidermis, we found that the mRNAs of both phospholipases A2 were expressed mainly in the basal layers of the epidermis. Our data thus provide evidence for the expression of two secretory phospholipases A2 in human epidermis. The different localization of these two secretory proteins strongly suggests that each enzyme might have a specific role in skin physiology and probably in the barrier function. Taken together, these data validate the reverse transcription-polymerase chain reaction technique performed on thin sections as a first approach to detect gene expression in different layers of the epidermis.
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Epiderme/enzimologia , Fosfolipases A/análise , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Humanos , Imuno-Histoquímica , Dados de Sequência Molecular , Fosfolipases A/genética , Fosfolipases A2 , RNA Mensageiro/análiseRESUMO
This review underlines the importance of different enzymes (beta-glucocerebrosidase, phospholipase A2, proteases and cholesterol sulfatase) in the formation and maintenance of the epidermal barrier function. Certain diseases may be characterized by the lack or excess of one or more of these different enzyme activities, altering the homeostatic equilibrium of the epidermis. In addition to this, particular enzymes may show potential in the development of novel dermocosmetic strategies.
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Epiderme/enzimologia , Homeostase/fisiologia , Dermatopatias/enzimologia , Animais , HumanosRESUMO
Confocal microscopy is an excellent method for studying the localization of fluorescent stains. Used in this way, superior 3D images can be obtained from multiple optical sections with very shallow depth of field. The main advantage of this technique is that the sample is not damaged. We have taken serial confocal sections of hair and via specific image enhancement routines have obtained high-quality 3D images enabling the visualization of cuticle scale and its pattern of distribution. This has been done on various types of hair: bleached, permed and in certain pathological conditions. This first step will allow us to characterize the hair surface in terms of its roughness, and the distribution and form of cuticular scale, parameters that have potential in the assessment of dermocosmetic efficacy.
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Cabelo/ultraestrutura , Processamento de Imagem Assistida por Computador , Microscopia Confocal/métodos , Doenças do Cabelo/patologia , Tinturas para Cabelo/farmacologia , Humanos , Microscopia Confocal/instrumentaçãoRESUMO
Skin surface enzyme activities were found to be significantly different in healthy and in skin with atopic dermatitis and, following appropriate treatment, a close correlation was observed between the clinical staging of the atopic dermatitis and the levels of the assayed marker enzymes. Samples were taken, by stripping with simple adhesive tapes, from a group of subjects on cure in a spa. The corneocytes were recovered from the first layers of the stratum corneum. Aqueous extracts of the strips were tested for their activity on chromophoric substrates which allow fluorescence spectrometry to be used to assay the trypsin-like, acid-phosphatase-like and phospholipase-A2-like activities. We show that the restoration of return to activities close to those of healthy subjects is related to the general condition of the patients, who showed a clearly improved SCORAD. Recovery of the trypsin-like activity and attenuation of the phospholipase-like activity, paralleled the regression of the dermatitis as assessed by a decrease in clinically evaluated parameters of xerosis and inflammation.
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Dermatite Atópica/enzimologia , Enzimas/metabolismo , Fosfatase Ácida/metabolismo , Adolescente , Adulto , Biomarcadores/análise , Criança , Dermatite Atópica/fisiopatologia , Dermatite Atópica/terapia , Feminino , Humanos , Masculino , Fosfolipases A/metabolismo , Fosfolipases A2 , Estatísticas não Paramétricas , Tripsina/metabolismoRESUMO
The report describes a method for the assay of five enzymatic activities involved in establishing the stratum corneum permeability barrier: beta-glucocerebrosidase, acid phosphatase, phospholipase A(2) (PLA(2)) and two serine proteases: chymotrypsin and its activator in the stratum corneum, trypsin. The specific activities of these different enzymes have been determined along with their pH profiles and sensivities to specific inhibitors. It can be noted that only two presented a pH optimum similar to the pH of the stratum corneum. This could suggest that their activities are regulated by local variations in pH. The method was applied to a pathological situation, that of a non-eczematous dry atopic dermatitis. Atopic skin had significantly reduced trypsin activity, increased acid phosphatase and no change in the activities of three other studied enzymes. Understanding these activities can provide a tool for the characterization of skin pathologies and for the development of a certain number of applications in cosmetology and therapeutics.
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Enzimas/análise , Pele/enzimologia , Fosfatase Ácida/análise , Adolescente , Adulto , Criança , Quimotripsina/análise , Dermatite Atópica/enzimologia , Inibidores Enzimáticos/farmacologia , Feminino , Glucosilceramidase/análise , Humanos , Concentração de Íons de Hidrogênio , Hidrólise , Indicadores e Reagentes , Masculino , Pessoa de Meia-Idade , Fosfolipases A/análise , Proteínas/análise , Pele/química , Pele/efeitos dos fármacos , Manejo de Espécimes , Tripsina/análiseRESUMO
Ultraviolet (UV) radiation has been shown to be responsible for different biological effects on human skin, including the initiation of photocarcinogenesis. Both UVB and UVA have been described as mutagenic, but the processes by which they alter the DNA are different. Although cells can repair DNA damage, some deleterious mutations nevertheless appear and can promote cancer. The risk of photocarcinogenesis is acknowledged and the frequency of photogenodermatosis is increasing. In order to evaluate the protection efficacy of a high sun protection factor (SPF) mineral sunscreen against UVB- and UVA-induced genomic alterations, we have followed two approaches. First, we have tested the sunscreen for its ability to decrease the unscheduled DNA synthesis response in vitro in human fibroblasts, as an indirect measure of UVB-induced lesions (0.005 and 0.01 J/cm2), and second, we have verified its ability to reduce the in situ end-labelling intensity in human skin as a direct measure of UVA-induced single-strand breaks (10 J/cm2). Microscopic analysis clearly demonstrated the protective effect of the sunscreen against UVB and UVA. A dose-dependent effect of mineral sunscreens was observed. There was also a relationship between the SPF and genomic protection. By limiting the accumulation of UV-induced lesions on DNA, this mineral sunscreen could limit the mutation frequency.
Assuntos
Dano ao DNA/efeitos da radiação , Fibroblastos/efeitos da radiação , Neoplasias Cutâneas/prevenção & controle , Protetores Solares/administração & dosagem , Titânio/administração & dosagem , Raios Ultravioleta/efeitos adversos , Óxido de Zinco/administração & dosagem , Adulto , DNA/biossíntese , DNA/efeitos da radiação , Reparo do DNA/efeitos da radiação , Relação Dose-Resposta a Droga , Feminino , Fibroblastos/metabolismo , Humanos , Pele/efeitos da radiaçãoRESUMO
Phospholipases A2 (PLA2) catalyse the release of fatty acids from the sn-2 position of phospholipids and have been suggested to play a key part in permeability barrier homeostasis. Using a sensitive and versatile fluorometric method, significant PLA2 activity has been detected in both human skin homogenates and tape strippings of stratum corneum. Based on various properties (resistance to heat and sulphuric acid treatment, neutral optimal pH, absolute requirement for millimolar calcium concentrations, inhibition by dithiothreitol and p-bromophenacyl bromide, and resistance to a trifluoromethyl ketone derivative of arachidonic acid, AACOCF3, a specific inhibitor of cytosolic PLA2), this enzyme was characterized as a secretory PLA2 (sPLA2). Immunohistochemistry revealed strong labelling of type I pancreatic sPLA2 at the stratum corneum-stratum granulosum junction, type II sPLA2 being undetectable. An increase in PLA2 activity in tape-stripped material from the deepest level of the stratum corneum was correlated with partial morphological disappearance of type I sPLA2 immunolabelling. Our data thus provide the first convincing evidence that pancreatic sPLA2 is significantly expressed in human epidermis, where it might participate in the accumulation of free fatty acids contributing to the permeability barrier. In addition, our method for determining PLA2 activity in easily available tape strippings should allow further clinical studies aimed to explore possible PLA2 abnormalities in various dermatoses.