RESUMEN
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Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Paniculitis/diagnóstico , Paniculitis/microbiología , Dermis/diagnóstico por imagen , Biopsia , Paniculitis/terapia , Formas Bacterianas Atípicas , Dermis/microbiología , Mesoterapia/efectos adversosRESUMEN
Skin mechanical properties are usually measured considering the entire skin thickness and very little is known about the mechanical behaviour of individual skin layers. We propose atomic force microscopy (AFM) as a tool to quantify nanoscale changes in the biomechanical properties and ultrastructure of human papillary dermis exposed to different mechanical and physical stimuli. Samples from 3 human skin biopsies were studied: one stretched by obesity, one subjected to a high level of sun exposure and normal skin as control. Slices of the papillary dermis layer were harvested at controlled depths from each skin biopsy and 25 µm2 areas of each slice were imaged and D-periodicity of collagen fibres measured by AFM, together with their stiffness. Standard histological analysis was also carried out to correlate biochemical properties and their distribution with stiffness and topography. We obtained similar stiffness values between the sample affected by obesity and the control sample at any depth level into the dermis, while the sun-exposed sample presented a significantly lower stiffness. Additionally, all samples presented an increase in the stiffness at higher depths into the papillary dermis layer. Collagen fibres close to the epidermis of sample affected either by obesity and sun exposure-the former even more than the latter-are thicker and present a larger D-period than those in the control sample. Our results open the possibility to use structural and mechanical analysis based on AFM as a complementary tool for medical diagnosis and therapy monitoring.
Asunto(s)
Dermis/patología , Epidermis/patología , Microscopía de Fuerza Atómica , Fenómenos Biomecánicos , Biopsia , Dermis/diagnóstico por imagen , Dermis/efectos de la radiación , Elasticidad , Humanos , Obesidad/complicaciones , Obesidad/metabolismo , Piel/patología , Estrés Mecánico , Quemadura Solar/complicacionesRESUMEN
Pseudoxanthoma elasticum (PXE) is a multisystem ectopic mineralization disorder caused by mutations in the ABCC6 gene. Warfarin, a commonly used anticoagulant, is associated with increased mineralization of the arterial blood vessels and cardiac valves. We hypothesized that warfarin may accelerate ectopic tissue mineralization in PXE, with clinical consequences. To test this hypothesis, we developed a model in which Abcc6(-/-) mice, which recapitulate features of PXE, were fed a diet supplemented with warfarin and vitamin K1. Warfarin action was confirmed by significantly increased serum levels of oxidized vitamin K. For mice placed on a warfarin-containing diet, quantitative chemical and morphometric analyses revealed massive accumulation of mineral deposits in a number of tissues. Mice fed a warfarin-containing diet were also shown to have abundant uncarboxylated form of matrix Gla protein, which allowed progressive tissue mineralization to ensue. To explore the clinical relevance of these findings, 1747 patients with PXE from the approximately 4000 patients in the PXE International database were surveyed about the use of warfarin. Of the 539 respondents, 2.6% reported past or present use of warfarin. Based on the prevalence of PXE (approximately 1:50,000), thousands of patients with PXE worldwide may be at risk for worsening of PXE as a result of warfarin therapy.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/deficiencia , Calcificación Fisiológica/efectos de los fármacos , Seudoxantoma Elástico/patología , Warfarina/efectos adversos , Transportadoras de Casetes de Unión a ATP/metabolismo , Animales , Calcio/sangre , Proteínas de Unión al Calcio/metabolismo , Dermis/diagnóstico por imagen , Dermis/efectos de los fármacos , Dermis/patología , Dieta , Suplementos Dietéticos , Modelos Animales de Enfermedad , Proteínas de la Matriz Extracelular/metabolismo , Humanos , Magnesio/metabolismo , Ratones , Minerales/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Especificidad de Órganos/efectos de los fármacos , Fosfatos/metabolismo , Fósforo/sangre , Seudoxantoma Elástico/sangre , Seudoxantoma Elástico/diagnóstico por imagen , Vitamina K/sangre , Warfarina/sangre , Microtomografía por Rayos X , Proteína Gla de la MatrizRESUMEN
Skin-targeted ultrasound is a noninvasive technique that has been extensively used to evaluate age-related dermal changes, and the presence of a subepidermal low-echogenic band (SLEB) has been related to chronic UVR exposure in several studies. Since SLEB echogenicity is photoage-related, the aim of this study was to evaluate, through ultrasound imaging, the effects on skin photoaging of mesotherapy, a treatment approach currently used in cosmetic dermatology for skin rejuvenation. Twenty women (mean age: 46.7 range 40-60 years) with physical signs of moderate photoaging on the dorsum of the hands were enrolled and treated with multiple microinjections of hyaluronic acid (HA) salts of biotechnological origin (1.000 Kd) every week for 4 weeks. In all subjects, ultrasound evaluation was performed at each visit and 1 week after the last treatment to evaluate SLEB echogenicity changes during treatment. At the end of study, a statistically significant (p < 0.001) increase of SLEB echogenicity (with a mean increase of pixel numbers equal to 31.3%) was observed in 15 of 19 subjects who completed the study. Our preliminary study suggests that mesotherapy with HA may be an effective treatment for skin photoaging, as confirmed by ultrasound. Follow-up investigations on larger series of patients are necessary to further evaluate the safety, effectiveness, and duration of effect of this possible therapeutic approach to skin photoaging.