No major impact of skin aging on the response of skin blood flow to a submaximal local thermal stimulus

La peau est sujette à un vieillissement intrinsèque (processus naturel et chronologique) et extrinsèque (processus induit par l'environnement et notamment les rayons UV). Plusieurs études ont montré que le vieillissement cutané s'accompagne d'une réduction de la densité capillaire au sein du derme et d'une dégradation de plusieurs protéines de la matrice extracellulaire. Cette atteinte morphologique est associée à une diminution de la capacité vasodilatatrice maximale de la microcirculation dermique et en particulier, de la réponse maximale du flux sanguin cutané à un échauffement local de la surface cutanée à des températures avoisinant les 43-44°C. Cette réponse, appelée hyperémie locale induite par la chaleur (local thermal hyperemia), est facilement mesurable par des investigations non invasives, telles que le laser Doppler. Nous avons entrepris cette étude afin d'investiguer les effets de l'âge sur la réactivité de la microcirculation dermique dans des zones cutanées exposées différemment aux rayons UV. Pour ce faire, nous avons étudié, chez des patients jeunes (18 à 30 ans, n=13) et des patients âgés (> 60 ans, n=13), la vasodilatation cutanée induite par réchauffement local de la peau, au niveau de 3 sites anatomiques différents (la cuisse, l'avant- bras et le front). Les mesures ont été effectuées au moyen d'un laser Doppler. Pour chaque sujet et chaque site, la température cutanée fut tout d'abord amenée à 34°C par 2 corps de chauffe (A et B), disposés de manière adjacente sur la peau. La température fut ensuite augmentée à 39°C (corps de chauffe A) et à 41°C (corps de chauffe B) pour une durée de 30 minutes, dans l'optique d'induire une vasodilatation sous- maximale. Ensuite, la température fut augmentée à 43 °C (corps de chauffe A et B) pour 15 minutes supplémentaires. Enfin, la vasodilatation maximale a été induite par un échauffement local à 44°C pour 15 minutes supplémentaires (corps de chauffe A et B). L'enregistrement séquentiel du flux sanguin cutané, effectué chaque minute par laser Doppler imager, donne des images sur lesquelles peut être calculé le flux sanguin cutané (unités de perfusion, PU). Par la suite, nous avons calculé les conductances vasculaires cutanées (CVC), en divisant le flux sanguin (PU) par la tension artérielle moyenne (mmHg), afin de permettre une normalisation entre les différents sujets. Les CVC, évaluées au temps de départ (température 34°C) et après vasodilatation maximale (température 44°C), étaient plus hautes au niveau du front qu'au niveau des 2 autres sites anatomiques. Sur les 3 sites, la CVC maximale (température 44°C) diminuait avec l'âge mais de façon moins importante au niveau du front, en comparaison avec les 2 autres sites. La réponse aux températures sous-maximales (température 39 et 41°C), exprimée en pourcentage de la CVC maximale, ne variait pas avec l'âge ni en fonction du site anatomique étudié. En conclusion, cette étude est la première à étudier simultanément l'hyperémie locale induite par la chaleur sur 3 sites ayant une exposition différente aux rayons UV. Le processus utilisé (laser Doppler imager) est également unique dans la littérature concernant les altérations de la microcirculation cutanée en lien avec l'âge. Cette étude confirme ainsi que le vieillissement cutané intrinsèque et/ou extrinsèque réduit la capacité vasodilatatrice maximale de la microcirculation dermique. Par contre, la réactivité à réchauffement local à des températures moindres ne semble pas être affectée.

No major impact of skin aging on the response of skin blood flow to a submaximal local thermal stimulus.

OBJECTIVE: This study was undertaken to investigate how aging affects dermal microvascular reactivity in skin areas differentially exposed to sunlight, and therefore to different degrees of photoaging. METHODS: We assessed, in young (18-30 years, n = 13) and aged males (≥60 years, n = 13), the thigh, forearm, and forehead's skin vasodilatory response to local heating (LTH) with a LDI. In each subject and at each location, local Tskin was brought from 34°C (baseline) to 39 or 41°C for 30 minutes, to effect submaximal vasodilation, with maximal vasodilation then elicited by further heating to 44°C. RESULTS: The CVCs evaluated at baseline and after maximal vasodilation (CVCmax ) were higher in the forehead than in the two other anatomical locations. On all locations, CVCmax decreased with age but less markedly in the forehead compared to the two other locations. When expressed in % of CVCmax , the plateau increase of CVCs in response to submaximal temperatures (39 and 41°C) did not vary with age, and minimally so with location. CONCLUSION: Skin aging, whether intrinsic or combined with photoaging, reduces the maximal vasodilatory capacity of the dermal microcirculation, but not its reactivity to local heating.

Skin Delivery of Kojic Acid-Loaded Nanotechnology-Based Drug Delivery Systems for the Treatment of Skin Aging

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Topical Application of Retinyl Palmitate-Loaded Nanotechnology-Based Drug Delivery Systems for the Treatment of Skin Aging

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Collagen Hydrolysate Intake Increases Skin Collagen Expression and Suppresses Matrix Metalloproteinase 2 Activity

The effect of daily ingestion of collagen hydrolysate (CH) on skin extracellular matrix proteins was investigated. Four-week-old male Wistar rats were fed a modified AIN-93 diet containing 12% casein as the reference group or CH as the treatment group. A control group was established in which animals were fed a non-protein-modified AIN-93 diet. The diets were administered continuously for 4 weeks when six fresh skin samples from each group were assembled and subjected to extraction of protein. Type I and IV collagens were studied by immunoblot, and activities of matrix metalloproteinase (MMP) 2 and 9 were assessed by zymography. The relative amount of type I and IV collagens was significantly (P<.05) increased after CH intake compared with the reference diet group (casein). Moreover, CH uptake significantly decreased both proenzyme and active forms of MMP2 compared with casein and control groups (P<.05). In contrast, CH ingestion did not influence on MMP9 activity. These results suggest that CH may reduce aging-related changes of the extracellular matrix by stimulating anabolic processes in skin tissue.

Development and Validation of a Clinical Scale for the Evaluation of Forearm Skin Photoaging

Background: Despite the focus on facial photoaging ratings, there are few classifications developed for forearm skin aging assessment.Objective: To develop and validate a clinical scale for the evaluation of forearm skin aging.Methods: Three clinical dermatology faculty members selected, discussed, and appraised the main signs of forearm photoaging. The validation of the resulting scale was performed by 5 assessors who were previously trained to classify 102 photographs of forearms with different degrees of aging. Retests were performed in 15 days.Results: There was significant correlation between the selected variables and the subjective global aging scale. The developed scale showed high internal consistency (Cronbach's alpha = 0.87) and high correlation with the global photoaging scale (rho = 0.92). Inter- and intraobserver final scores showed high agreement.Conclusion: A validated clinical photoaging scale for forearms with internal consistency, reliability, and validity was developed.

Development of an anti aging cream with AHA/BHA and sunscreens

The skin aging is a matter of discomfort verified in the population. Thus, every day, new products are launched on the market to offer different manners to prevent the premature aging of the skin. In this context, active substances, as alpha and beta hidroxyacids (AHA/BHA), beyond the sunscreens, are considered a way of prevention and amelioration of the effects caused in the skin due to the time. The aim of this study was to develop and evaluate a cosmetic cream containing AHA/BHA and sunscreen. It was studied in relation to its physical-chemical and microbiological characteristics. According to the results, the formulation developed present a shelf life of 758 days and the preservative system was effective. Considering the parameters evaluated, the cream probably would be commercially accepted.

Development of an anti-aging cream with AHA/BHA and sunscreens

The skin aging is a matter of discomfort verified in the population. Thus, every day, new products are launched on the market to offer different manners to prevent the premature aging of the skin. In this context, active substances, as alpha and beta hidroxyacids (AHA/BHA), beyond the sunscreens, are considered a way of prevention and amelioration of the effects caused in the skin due to the time. The aim of this study was to develop and evaluate a cosmetic cream containing AHA/BHA and sunscreen. It was studied in relation to its physical-chemical and microbiological characteristics. According to the results, the formulation developed present a shelf life of 758 days and the preservative system was effective. Considering the parameters evaluated, the cream probably would be commercially accepted.

Clues to epidermal cancer proneness revealed by reconstruction of DNA repair-deficient xeroderma pigmentosum skin in vitro

Sun exposure has been clearly implicated in premature skin aging and neoplastic development. These features are exacerbated in patients with xeroderma pigmentosum (XP), a hereditary disease, the biochemical hallmark of which is a severe deficiency in the nucleotide excision repair of UV-induced DNA lesions. To develop an organotypic model of DNA repair deficiency, we have cultured several strains of primary XP keratinocytes and XP fibroblasts from skin biopsies of XP patients. XP skin comprising both a full-thickness epidermis and a dermal equivalent was succesfully reconstructed in vitro. Satisfactory features of stratification were obtained, but the expression of epidermal differentiation products, such as keratin K10 and loricrin, was delayed and reduced. In addition, the proliferation of XP keratinocytes was more rapid than that of normal keratinocytes. Moreover, increased deposition of cell attachment proteins, α-6 and β-1 integrins, was observed in the basement membrane zone, and β-1 integrin subunit, the expression of which is normally confined to basal keratinocytes, extended into several suprabasal cell layers. Most strikingly, the in vitro reconstructed XP skin displayed numerous proliferative epidermal invasions within dermal equivalents. Epidermal invasion and higher proliferation rate are reminiscent of early steps of neoplasia. Compared with normal skin, the DNA repair deficiency of in vitro reconstructed XP skin was documented by long-lasting persistence of UVB-induced DNA damage in all epidermal layers, including the basal layer from which carcinoma develops. The availability of in vitro reconstructed XP skin provides opportunities for research in the fields of photoaging, photocarcinogenesis, and tissue therapy.

Dermatologie esthétique et correctrice: applications cliniques et rôle social [Esthetic and corrective dermatology: clinical applications and social role].

Skin diseases may have severe aesthetic and psychological repercussions leading sometimes to discriminations and social isolation. Dermatologists have contributed to the development of many cosmetic procedures: peelings, botulinum toxin or hyaluronic acid injections, lasers, blepharoplasty, facelift, etc. Many of these treatments have interesting clinical applications and may help numerous patients with skin diseases to return to a normal social life.

Mechanisms of Photoaging and Cutaneous Photocarcinogenesis, and Photoprotective Strategies with Phytochemicals.

Photoaging and photocarcinogenesis are primarily due to solar ultraviolet (UV) radiation, which alters DNA, cellular antioxidant balance, signal transduction pathways, immunology, and the extracellular matrix (ECM). The DNA alterations include UV radiation induced thymine-thymine dimers and loss of tumor suppressor gene p53. UV radiation reduces cellular antioxidant status by generating reactive oxygen species (ROS), and the resultant oxidative stress alters signal transduction pathways such as the mitogen-activated protein kinase (MAPK), the nuclear factor-kappa beta (NF-κB)/p65, the janus kinase (JAK), signal transduction and activation of transcription (STAT) and the nuclear factor erythroid 2-related factor 2 (Nrf2). UV radiation induces pro-inflammatory genes and causes immunosuppression by depleting the number and activity of the epidermal Langerhans cells. Further, UV radiation remodels the ECM by increasing matrixmetalloproteinases (MMP) and reducing structural collagen and elastin. The photoprotective strategies to prevent/treat photoaging and photocarcinogenesis include oral or topical agents that act as sunscreens or counteract the effects of UV radiation on DNA, cellular antioxidant balance, signal transduction pathways, immunology and the ECM. Many of these agents are phytochemical derivatives and include polyphenols and non-polyphenols. The flavonoids are polyphenols and include catechins, isoflavones, proanthocyanidins, and anthocyanins, whereas the non-flavonoids comprise mono phenolic acids and stilbenes. The natural sources of polyphenols include tea, cocoa, grape/wine, soy, pomegranate, and Polypodium leucotomos. The non-phenolic phytochemicals include carotenoids, caffeine and sulphoraphance (SFN). In addition, there are other phytochemical derivatives or whole extracts such as baicalin, flavangenol, raspberry extract, and Photomorphe umbellata with photoprotective activity against UVB radiation, and thereby carcinogenesis.

Ultraweak photon emission in assessing bone growth factor efficiency using fibroblastic differentiation.

Photons participate in many atomic and molecular interactions and changes. Recent biophysical research has shown the induction of ultraweak photons in biological tissue. It is now established that plants, animal and human cells emit a very weak radiation which can be readily detected with an appropriate photomultiplier system. Although the emission is extremely low in mammalian cells, it can be efficiently induced by ultraviolet light. In our studies, we used the differentiation system of human skin fibroblasts from a patient with Xeroderma Pigmentosum of complementation group A in order to test the growth stimulation efficiency of various bone growth factors at concentrations as low as 5 ng/ml of cell culture medium. In additional experiments, the cells were irradiated with a moderate fluence of ultraviolet A. The different batches of growth factors showed various proliferation of skin fibroblasts in culture which could be correlated with the ultraweak photon emission. The growth factors reduced the acceleration of the fibroblast differentiation induced by mitomycin C by a factor of 10-30%. In view that fibroblasts play an essential role in skin aging and wound healing, the fibroblast differentiation system is a very useful tool in order to elucidate the efficacy of growth factors.

Antioxidantes na manutenção do equilíbrio redox cutâneo: uso e avaliação de sua eficácia

The skin is a very complex organ, continuously exposed to physical, chemical and microbiological agents. Enzymes as well as low-molecular weight antioxidants are present in the cutaneous tissue to counterbalance the deleterious effect caused by an oxidative stress and thus maintain homeostasis. Antioxidants such as vitamins C and E, carotenoids, and extracts with these properties have been extensively used for treatment of pathologies and skin aging prevention. We review here different mechanisms that can interfere in the redox equilibrium of the skin, as well as the chemical reactions involved in these processes. Moreover, we discuss the importance of endogenous or exogenous antioxidants that can be acquired from the diet or from oral or topical administration, and methodologies that have been developed to evaluate their efficacy.

Factores comportamentales hacia la fotoprotección

Introducción: la fotoprotección constituye las actividades preventivas que minimizan los efectos deletéreos de la exposición solar; estos comportamientos de salud pueden estar relacionados con actitudes y conocimientos adquiridos. Objetivo: Identificar estas asociaciones en Estudiantes de Medicina de la Escuela de Medicina y Ciencias de la Salud de la Universidad del Rosario, quienes se encargarán de transmitir educación y ejemplo de comportamiento en su contexto personal y profesional. Metodología: estudio de corte transversal. Se implementó una encuesta voluntaria por correo institucional y físicamente entre estudiantes de 1-8 semestre matriculados en el segundo semestre de 2009; n= 122 estudiantes, la mayoría menores de 20 años y de género femenino; factores de estudio analizados: biológico – demográficos, informador, actitudes, conocimientos, personas modelo y comportamiento, expresados en frecuencias, analizados con pruebas y fuerzas de asociación con intervalo de confianza del 95%. Resultados: factores asociados a fotoprotección: ser de 1-4 semestre (p=0,008), ser =19 años (p=0,028), reconocer como consecuencias las alteraciones en los ojos y la visión (p=0,043) y las alteraciones producidas en el sistema inmune (p=0,021), uso de la pareja de ropa protectora (p=0,019), permanencia de un amigo a la sombra (p=0,055), conocimiento de la posibilidad de quemadura independiente al clima (p=0,001) y conocimiento de la posibilidad de quemadura sin sentir los rayos calientes del sol (p=0,049). Conclusiones: es posible reforzar comportamientos preventivos, favorecer el seguimiento de modelos positivos afines a los jóvenes, incrementar el conocimiento en salud y afirmar la educación primaria en salud desde la Medicina General y mejorar así la fotoprotección.

Construcción de una guía fotográfica para valorar el grado de fotoenvejecimiento cutáneo del dorso de las manos

Introducción: La exposición crónica al sol es la principal causa ambiental de envejecimiento cutáneo. (1) Pese a que existen clasificaciones exclusivas de fotoenvejecimiento a nivel facial, no existen, con estas características a nivel de manos. El objetivo de este estudio fue elaborar una guía fotográfica para identificar fotoenvejecimiento en el dorso de manos. Materiales y metodos: En la primera fase se seleccionaron nueve características del puntaje SCINEXA, utilizadas en la fase dos por un grupo de cinco expertos para definir cuatro grados de severidad del fotoenvejecimiento de las manos. En la fase tres otros seis expertos clasificaron en 150 fotografías estandarizadas el grado de fotoenvejecimiento de las manos teniendo en cuenta los grados definidos. Por último se realizó análisis estadístico para valorar la concordancia inter evaluadores y se tomaron las fotos con mejor concordancia para la construcción de la guía fotográfica. Resultados: La valoración de las características tomadas para cada grado de fotoenvejecimiento de las manos tuvo una concordancia casi del 100%, mientras que la concordancia global interevaluadores de las 150 fotografías fue del 41.1%. La mejor concordancia interevaluadores se dio para el grado 0 (57,2%). Discusión: Las escalas fotográficas de las manos con que se contaba están más orientadas a definir los grados de envejecimiento tomando a la vez signos de crono y fotoenvejecimiento, por su parte la guía fotográfica obtenida en este estudio valora únicamente el fotoenvejecimiento siendo esta una herramienta ideal para evaluar la eficacia de tratamientos cuyo propósito sea el de mejorar el fotodaño cutáneo.