Article

Extracellular matrix in cutaneous ageing: The effects of 0.1% copper-zinc malonate-containing cream on elastin biosynthesis

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Abstract

Cutaneous ageing, as visualized at the exposed areas of skin, reflects dramatic alterations in the structure and function of the extracellular matrix of connective tissues. Among them, the elastic fibre network, which is responsible for the physiological elasticity and resilience of normal skin, undergoes degradative changes leading to loss of functional elastic fibres. A potential strategy to counteract these degenerative changes entails topical application of a compound that may lead to regeneration of the elastic fibre network. In this study, we have evaluated the effects of a bi-metal, 0.1% copper-zinc malonate-containing cream that has been shown to efface wrinkles in clinical trials. An effect on elastin biosynthesis and elastic tissue accumulation in skin biopsies was observed in 21 female patients with photoaged facial skin, as measured at baseline and at 6 weeks of treatment. Histopathological evaluation revealed evidence of elastic fibre regeneration, including those extending perpendicularly towards the dermo-epidermal junction within the papillary dermis. Elastin biosynthesis, measured by semi-quantitative immunofluorescence with an antibody recognizing only the newly synthesized, uncrosslinked tropoelastin molecules, suggested statistically significant enhancement of elastin biosynthesis by the bi-metal compound when applied twice daily. Accumulation of elastic fibres was confirmed by assay of desmosine, an elastin-specific crosslink compound. These results suggest that the bi-metal, 0.1% copper-zinc malonate-containing cream has the propensity to increase elastin synthesis in human skin in vivo, and that regeneration of elastic fibres may contribute to wrinkle effacement in female patients with photoaged facial skin.

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... Cutaneous ageing seen on exposed areas of the skin secondary to significant alterations in the structure and function of the extracellular matrix of the connective tissues [93] Unknown ...
... The efficacy of topical Zn preparation has been shown in treating this condition [93]. ...
... Cutaneous ageing, as seen on exposed areas of the skin, reflects significant alterations in the structure and function of the extracellular matrix of the connective tissues particularly the collagen and elastic fibers. The aging process consists of two clinically and biologically distinct components including innate skin aging, inflicts the skin in a similar age-associated progressive manner, and extrinsic ageing, secondary to exposure to environment, especially ultraviolet (UV) irradiation [93]. ...
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Abstract Zinc is an essential trace element important for a large number of structural proteins, enzymatic processes and transcription factors. It plays main roles in the cell-mediated immunity, bone formation, tissue growth, brain function, growth of the fetus and child. It also has roles in pathogenesis of some dermatological disorders. Zinc can be used as effective agent for treatment of some skin and hair disorders, but generally, it seems that with the exception of states relating to zinc deficiency, there is very little evidence to support the efficacy of zinc as a first-line treatment for most of dermatological conditions. Herein, we collected and summarized the appropriate manuscripts and papers regarding the importance of zinc in some of the most important dermatological disorders.
... To detect tropoelastin, the microprobe system (Fisher Thermo Scientific #FD-188-10A) was used with reagents from Open Biosystems (Huntsville, AL, USA) (13,18). Antibodies used were tropoelastin GA317 (1:400; Elastin Products, Owensville, MO, USA) and Alexa Fluor goat anti-rabbit IgG 594 (1:400; Molecular Probes). ...
... Normal elastic fibers, which are responsible for the resilient properties of the skin, constitute less than 2-4% of the extracellular matrix in sun protected areas (6,7,18). The hallmark feature of photoaging is dermal/solar elastosis whereby the elastic fibers appear disorganized, thickened and tangled. ...
... The biosynthesis rate of normal elastin was evaluated by quantifying for newly synthesized tropoelastin, the precursor of elastic fibers (18). Compared to the base line, morphometric analysis of tropoelastin stained sections showed a statistically significant increase in the mean level from 9.7 ± 2.4 % to 13.5 ± 2.1 % (p = 0.02) at the end of Er:YAG mini-peels and to 13.1 ± 1.1 % at 3 months post treatment (p = 0.04) (Table II and Figures 3A and B). ...
Article
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As the demand for minimally invasive rejuvenation is increasing, micropeel resurfacing using Erbium:Yttrium Aluminum Garnet (Er:YAG) laser 2940 nm has been reported for the treatment of photoaged skin without ablation of the epidermis. However, little is known about the efficacy and underlying histologic changes associated with this type of treatment. The aims of this study are to evaluate the clinical effect and objectively quantify the histological changes in response to multiple sessions of Er:YAG laser 2940 nm mini-peels. Six female volunteers of Fitzpatrick skin type III-IV and Glogau's class I-III wrinkles were subjected to six microresurfacing peels at 2-week intervals using Er:YAG 2940 nm laser at subablative fluences of 2-3 J/cm(2) to treat periorbital rhytides. Quantitative evaluation of collagen types I, III, and VII, newly synthesized collagen, total elastin, and tropoelastin was performed by histochemistry and immunohistochemistry coupled with computerized morphometric analysis at base line, end of treatment, and 3 months post-treatment. Compared to the base line, evaluation of volunteers revealed obvious clinical improvement in response to Er:YAG mini-peels. Collagen types I, III, and VII, as well as newly synthesized collagen, together with tropoelastin showed a statistically significant increase in response to treatment, while the mean level of total elastin was significantly decreased in response to treatment. However, this was followed by regression of improvement at 3 months post-treatment but was still better than baseline. This study revealed that multiple Er:YAG mini-peels is a promising treatment option for photoaging as it reverses the signs of photoaged skin with little downtime and side effects. However, to maintain the short-term improvement achieved after treatment, continued Er:YAG 2940 nm laser mini-peels is required.
... For tropoelastin, the authors used the microprobe system (Fisher Scientific #FD-188-10A) with reagents from Open Biosystems (Huntsville, Alabama) as previously described. 13 Tissues were incubated with blocking buffer (5% normal goat serum, 1% BSA and 0.01% Triton-X-100 in PBS), tropoelastin antibody GA317 (1:400; Elastin Products, Owensville, Missouri), and Alexa Fluor goat anti-rabbit IgG 594 secondary antibody (1:400; Molecular Probes). All histometric evaluations were carried out using computerbased software (Image-Pro Plus; Media Cybernetics, Silver Spring, Maryland). ...
... Elastic fibers are composed mainly of elastin, a connective tissue protein which is initially synthesized as tropoelastin. 13 Thus, the authors evaluated the rate of elastin biosynthesis by quantifying newly synthesized tropoelastin. Compared to the baseline, the results showed a significant increase in the mean of tropoelastin from 14.9±3.5 percent to 19.7±2.4 percent at the end of treatment, and 19.5±1.5 percent three months posttreatment (p≤0.021 and 0.026, respectively) ( Figures 3A and 3B). ...
... In photoaged skin, there is an ongoing proteolytic degradation of normal elastic fibers, combined with distinctly decreased normal elastin biosynthesis. 13 Accordingly, the authors assessed the changes in the level of tropoelastin, the precursor of elastin biosynthesis. The results showed a significant increase in the levels of tropoelastin at the end of treatment, which remained high three months post-treatment ( Figure 3A). ...
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Objectives: Electro-optical synergy technology is one of the most recently described methods for nonablative skin rejuvenation. The aim of this study is to evaluate the effects of electro-optical synergy on connective tissue composition by histological and immunohistochemical techniques coupled with computerized morphometric analysis. Design: A prospective clinical study. Participants: Six volunteers with Fitzpatrick skin types 3 to 4 and Glogau class I to II wrinkles were subjected to three months (6 sessions at 2-week intervals) of electro-optical synergy treatment. Measurements: Standard photographs and skin biopsies were obtained at baseline as well as three and six months after the start of treatment. The authors performed quantitative evaluation of total elastin, tropoelastin, collagen types I, III, and VII, and newly synthesized collagen. Results: Noticeable clinical and histological improvement was observed after electro-optical synergy treatment. A statistically significant increase in the means of collagen types I, III, and VII, as well as newly synthesized collagen, together with increased levels of tropoelastin, were detected, while the mean level of total elastin was significantly decreased at the end of treatment and three months post-treatment. Conclusion: Electro-optical synergy is an effective treatment for contouring facial skin laxity. This modality stimulates the repair processes and reverses the clinical, as well as the histopathological, signs of aging with the advantage of being a relatively risk-free procedure with minimal patient recovery time.
... On the other hand, Zinc (present in cream-gel as Zinc salt of PCA) was hypothesized to play a more active anti-wrinkle role at the biological level. Zinc is an essential cofactor reported to regulate the function of metalloenzymes and transcription factors [37], including those responsible for the synthesis of collagen [38] and elastin [39]. This ingredient is widely used as a therapeutic agent alone or in combination in a number of dermatological conditions and also in anti-aging [37]. ...
... Additionally, we found a significant increase in elastin fibers after topical application of the test products on human skin explants. Regeneration of elastin fibers has been described in vivo using anti-wrinkle agents [39,47]. ...
Article
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Skin aging is a biological process leading to visible skin alterations. The mechanism of action, clinical efficacy and tolerance of a novel anti-wrinkle technology were evaluated in two skin care products formulated for different skin types. Two single-arm monocentric, open-label observational clinical studies, which were 56 days long, evaluated a cream-gel (n = 30) and a cream (n = 33) on the face and neck. Morphometric analyses of five types of wrinkles were performed at 0, 7, 28 and 56 days. Structural changes in extracellular matrix (ECM) including collagen, elastin and hyaluronic acid (HA) were visualized and quantified by histochemical imaging after daily treatment of skin explants for 6 days. Protein and gene expression related to barrier and hydration were analyzed using ELISA and qRT-PCR, respectively, in a reconstituted human skin model treated daily for 48 h. A decrease in wrinkle dimensions was found in the majority of parameters after 28 days of treatment. Collagen, elastin, HA, procollagen type I, hyaluronan synthases, HAS2 and HAS3 were all stimulated. Based on significant and consistent changes in our investigations, we conclude that the underlying mechanism of action of the novel anti-wrinkle technology could be the remodeling of dermal ECM, and both the test formulations were efficacious and well tolerated.
... Clinical tests of cosmetic products containing copper-zinc malonate reported significant reduction of wrinkles after 8 -weeks of treatment. This result was supported by molecular and histological data showing regeneration of elastic fibre network in treated sites, which was due to enhanced synthesis of tropoelastin (Mahoney et al., 2009). ...
... Finally, zinc in association with copper, enhances regeneration of elastic fibres within dermis, which results in the reduction of wrinkles (Mahoney et al., 2009). ...
Article
Skin constitutes a barrier protecting the organism against physical and chemical factors. Therefore, it is constantly exposed to the xenobiotics, including inorganic ions that are ubiquitous in the environment. Some of them play important roles in homeostasis and regulatory functions of the body, also in the skin, while others can be considered dangerous. Many authors have shown that inorganic ions could penetrate inside the skin and possibly induce local effects. In this review, we give an account of the current knowledge on the effects of skin exposure to inorganic ions. Beneficial effects on skin conditions related to the use of thermal spring waters are discussed together with the application of aluminium in underarm hygiene products and silver salts in treatment of difficult wounds. Finally, the potential consequences of dermal exposure to topical sensitizers and harmful heavy ions including radionuclides are discussed.
... Copper-containing cream has previously been tested for its capacity to reduce facial wrinkling [76]. Histopathological examination of skin biopsies demonstrated an increased number of elastin crosslinks after 6 weeks of topical copper therapy, providing a proof of principle for the feasibility of elastin regenesis in human adults [76]. ...
... Copper-containing cream has previously been tested for its capacity to reduce facial wrinkling [76]. Histopathological examination of skin biopsies demonstrated an increased number of elastin crosslinks after 6 weeks of topical copper therapy, providing a proof of principle for the feasibility of elastin regenesis in human adults [76]. Given the association between the severity of facial wrinkling and lung emphysema [77], we would expect that copper will also have an activating effect on LOX-mediated elastin crosslinking in lungs. ...
Article
Introduction: Current pharmacologic therapy of chronic obstructive pulmonary disease (COPD) can reduce respiratory symptoms and exacerbation frequency. However, no single COPD intervention except for lung transplantation has proven effective in recovering lung function. Lung elasticity is reduced in COPD lungs, which is for a large part due to chronically enhanced elastin degradation. Elastin calcification and formation of advanced glycation end products (AGEs) may also contribute to this. Areas covered: We propose inhalation therapy to induce repair of damaged pulmonary elastin fibers by stimulating tropoelastin synthesis, assembly and crosslinking in order to improve lung function in patients with COPD. Decelerating elastinolysis is another treatment objective, as well as decalcification and deglycation of the extracellular matrix. Expert commentary: Studies should be conducted to test whether it is feasible to restore pulmonary elastin fibers with inhalation therapy. We expect that the optimal formulation will turn out to be a combination of copper, epigallocatechin-(3-)gallate or pentagalloyl glucose, vitamin A/D/K, magnesium, heparin or heparan sulfate, minoxidil and one or more AGEs-inhibitors. Establishing a treatment that has the proven ability to facilitate regain of lost lung function in COPD patients would cause a major paradigm shift in this debilitating disease.
... Elastic fibers, which are responsible for the elasticity and resilience of normal human skin, constitute <2-4% of the extracellular matrix. 14,20,21 The accumulation of thickened, tangled, and amorphous elastic structures in the dermis is known as solar elastosis and represents the histopathological mark of skin aging. [21][22][23][24] The effect of mesotherapy injection on total dermal elastin was examined by measuring the percentage area of dermis occupied by immunohistochemically detectable elastin; values were then normalized to baseline. ...
... Elastic fibers are composed mainly of elastin, which is initially synthesized as tropoelastin. 4,14 The biosynthetic rate of elastin was evaluated by quantifying newly synthesized tropoelastin. Mesotherapy injection did not appear to bring about any significant differences between tropoelastin levels prior to treatment (13.6 ± 1.3%) and levels at the end of treatment (13.9 ± 3.3%; P = 0.636) or at three months post-treatment (13.0 ± 1.9%; P = 0.586) ( Table 1, Fig. 3b,c). ...
Article
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Mesotherapy, commonly known as "biorejuvenation" or "biorevitalization", is a technique used to rejuvenate the skin by means of a transdermal injection of a multivitamin solution and natural plant extracts that are thought to improve the signs of skin aging. This prospective study aimed to evaluate the clinical effect of mesotherapy applied to periorbital wrinkles and to quantitatively evaluate histological changes in the skin occurring in response to the same treatment. Six volunteers with Fitzpatrick skin types III or IV and Glogau class I-III wrinkles were subjected to a three-month course of mesotherapy injections in the periocular area (six sessions administered at two-week intervals). Standard photographs and skin biopsies were obtained from the treatment area at baseline, at the end of treatment, and at three months post-treatment. Quantitative evaluation of collagen types I, III, and VII, newly synthesized collagen, total elastin, and tropoelastin was performed using a computerized morphometric analysis. The clinical evaluation of volunteers at baseline, end of treatment, and three months post-treatment revealed no significant differences. Histological and immunostaining analysis of collagen types I, III, and VII, newly synthesized collagen, total elastin, and tropoelastin showed no statistically significant changes (P > 0.05) after mesotherapy injection. The present study indicates that mesotherapy for skin rejuvenation does not result in statistically significant histological changes or clinical improvement.
... The microprobe system (Fisher Thermo Scientific #FD-188-10A) was used to detect tropoelastin with reagents from Open Biosystems (Huntsville, AL). 16,17 Antibodies used were tropoelastin GA317 (1:400; Elastin Products, Owensville, MO) and Alexa Fluor goat anti-rabbit IgG 594 (1:400; Molecular Probes). For nuclear staining, tissues were incubated with DAPI. ...
... The biosynthesis rate of normal elastin was evaluated by quantifying for newly synthesized tropoelastin, the precursor of elastic fibers. 16,17 IPL treatment didn't show statistically significant differences in tropoelastin levels as it increased from 12.4±2.6% before treatment to 13.3±3.3% ...
Article
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The use of intense pulsed light (IPL) for facial rejuvenation had been the topic of many studies. However, few of them discussed quantitative changes in extracellular matrix proteins after IPL therapy. To objectively quantify the histological changes in extracellular matrix proteins after IPL treatment for facial wrinkles. Biopsy specimens were obtained from the periocular area of six volunteers of Fitzpatrick skin type III-IV and Glogau's class I-III wrinkles. They were subjected to three months of IPL treatment (six sessions at two-week intervals). Using histological and immunostaining analysis coupled with computerized morphometric analysis, quantitative evaluation of collagen types I, III and VII, newly synthesized collagen, total elastin and tropoelastin was performed for skin biopsies at baseline, end of treatment, and three months post-treatment. Clinical assessment of volunteers did not show clinically noticeable improvement in facial wrinkles after IPL treatment. Furthermore, quantitative evaluation of extracellular matrix proteins showed no statistically significant changes (P>0.05) in response to IPL treatment Although 50 percent of volunteers showed mild improvement in skin texture at the end of IPL treatment, none of them reported improvement in skin tightening or wrinkles. No statistically significant histological changes were observed three months post IPL treatment.
... Como resultado, os pesquisadores realizaram o uso da substância duas vezes ao dia, tendo como melhorando cerca de 49,78% (Sharquie, et al., 2008). Outro estudo realizado por Mahoney et al., 2009, demonstrou resultados positivos no uso de zinco na biossíntese de elastina com uma preparação tópica de 0,1% de cobre-zinco. Como consequências dos estudos, houve restauração progressiva da rede de fibra elástica com uso da preparação durante 6-8 semanas, comprovando a substância pode ser usada para o melhoramento de rugas da pele facial fotoenvelhecida. ...
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A pele é o maior órgão do corpo humano e seu estado reflete intimamente o estado de saúde em que o complexo organismo humano se encontra. Além disso, a pele está exposta diariamente a danos ambientais que podem acarretar envelhecimento precoce, hiperpigmentações, desidratação e até mesmo doenças de pele, como o câncer. Junto com aumento da expectativa de vida tem-se buscado cada vez mais, alternativas que possibilitem a manutenção da saúde da pele, a fim de protegê-la contra os danos nocivos do ambiente ou sintomas de degeneração celular, com consequentes hiperpigmentações, fotoenvelhecimento e até mesmo o câncer de pele. Diante disso, as ciências da nutrição juntamente com a medicina estética se fazem conjuntamente presentes, visto que a pele se mostra como indicador sensível de deficiências nutricionais. Para tanto, para a manutenção de uma pele saudável é preciso nutri-la com nutrientes importantes para o corpo através de uma dieta diversificada e balanceada. Muitos compostos agem de forma efetiva na prevenção do envelhecimento da pele, com comprovações em modelos in vitro, animais e humanos. O objetivo desse estudo, portanto, foi revisar a literatura para demonstrar como as substâncias bioativas presentes na dieta influenciam no processo de envelhecimento e sua importância nos aspectos físicos da pele como hidratação, elasticidade, coloração, firmeza e rugas.
... [41][42][43][44] Topical approaches have attempted to exploit a wide range of mechanisms, such as copper and zinc that are A c c e p t e d M a n u s c r i p t components). 41,42,[45][46][47] However, given the complexity of tropoelastin production, assembly, and crosslinking, there is limited evidence that topical skincare products can reach the dermal layers of the skin or sufficiently stimulate elastin production. 18 Some studies have proposed that these products can stimulate elastin production or remodeling based on changes in dermal markers observed via histologic testing, biopsy, subjective patient feedback, or measurement of mechanical skin properties by probe and suction devices. ...
... [41][42][43][44] Topical approaches have attempted to exploit a wide range of mechanisms, such as copper and zinc that are A c c e p t e d M a n u s c r i p t components). 41,42,[45][46][47] However, given the complexity of tropoelastin production, assembly, and crosslinking, there is limited evidence that topical skincare products can reach the dermal layers of the skin or sufficiently stimulate elastin production. 18 Some studies have proposed that these products can stimulate elastin production or remodeling based on changes in dermal markers observed via histologic testing, biopsy, subjective patient feedback, or measurement of mechanical skin properties by probe and suction devices. ...
Article
Full-text available
Elastin is the main component of elastic fibers, which provide stretch, recoil, and elasticity to the skin. Normal levels of elastic fiber production, organization, and integration with other cutaneous extracellular matrix proteins, proteoglycans, and glycosaminoglycans are integral to maintaining healthy skin structure, function, and youthful appearance. Although elastin has very low turnover, its production decreases after individuals reach maturity and it is susceptible to damage from many factors. With advancing age and exposure to environmental insults, elastic fibers degrade. This degradation contributes to the loss of the skin’s structural integrity; combined with subcutaneous fat loss, this results in looser, sagging skin, causing undesirable changes in appearance. The most dramatic changes occur in chronically sun-exposed skin, which displays sharply altered amounts and arrangements of cutaneous elastic fibers, decreased fine elastic fibers in the superficial dermis connecting to the epidermis, and replacement of the normal collagen-rich superficial dermis with abnormal clumps of solar elastosis material. Disruption of elastic fiber networks also leads to undesirable characteristics in wound healing, and the worsening structure and appearance of scars and stretch marks. Identifying ways to replenish elastin and elastic fibers should improve the skin’s appearance, texture, resiliency, and wound-healing capabilities. However, few therapies are capable of repairing elastic fibers or substantially reorganizing the elastin/microfibril network. This review describes the clinical relevance of elastin in the context of the structure and function of healthy and aging skin, wound healing, and scars and introduces new approaches being developed to target elastin production and elastic fiber formation.
... Zinc is used to treat numerous dermatological conditions, such as infections (e.g., warts), inflammatory dermatoses (acne vulgaris, rosacea, atopic dermatitis and alopecia areata) and pigmentary disorders (melasma) [97][98][99]107,110]. Zinc administered orally or topically has been shown to have therapeutic applications in skin ageing (a 0.1% copperzinc malonate cream applied topically for 6 weeks significantly reduced wrinkles) [111]; melasma (a 10% zinc sulphate solution applied topically twice daily for 2 months significantly reduced MASI scores) [112]; actinic keratoses (a 25% zinc sulphate solution applied topically twice daily for 12 weeks was safe and effective, especially in patients with multiple actinic keratosis lesions) [113]; xeroderma pigmentosum (a 20% topical application of a zinc sulphate solution for 4 months to 2 years improved all types of skin lesions, softened the skin, lightened the skin color, and cleared the skin of solar keratosis and small malignancies) [114]; eczema (a 0.05% Clobetasol + 2.5% zinc sulphate cream applied topically was effective in hand eczemas) [115]; rosacea (100 mg of oral zinc sulphate three times per day was effective after 3 months of therapy) [116]; and alopecia areata (5 mg/kg/day, in three divided doses, of oral zinc sulphate induced significant hair growth after 6 months) [117]. ...
Article
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Human skin is continually changing. The condition of the skin largely depends on the individual’s overall state of health. A balanced diet plays an important role in the proper functioning of the human body, including the skin. The present study draws attention to bioactive substances, i.e., vitamins, minerals, fatty acids, polyphenols, and carotenoids, with a particular focus on their effects on the condition of the skin. The aim of the study was to review the literature on the effects of bioactive substances on skin parameters such as elasticity, firmness, wrinkles, senile dryness, hydration and color, and to define their role in the process of skin ageing.
... 58 Soy and rice extracts might also increase elastin formation, as has been reported for a combination of zinc and copper. 59,60 More recently, a dill extract has also been shown to have the potential to promote elastin formation by promoting LOXL synthesis and secretion into E57 JCAD JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY September 2020 • Volume 13 • Number 9 R E V I E W the dermis. 61,62 CONCLUSION MDE is a rare, female-centric skin condition that is associated with aesthetic implications and significant psychosocial impact. ...
Article
We provide a brief review on mid-dermal elastolysis (MDE) and summarize clinical data of 105 patients with MDE who were reported in the literature since the disease was first described in 1977. In doing so, emphasis is placed on pathomechanisms and therapeutic aspects. MDE is a rare, acquired skin disease histopathologically characterized by selective loss of elastic fibers in the mid-dermis. Lesions are commonly observed on the trunk and proximal extremities. These include well-circumscribed patches of fine wrinkles, perifollicular papular protrusions, and persistent reticular erythema. With respect to pathomechanisms, current data suggest that different cell types (e.g., macrophages, fibroblasts) might chronically overexpress matrix metalloproteinases resulting in an enhanced elastolytic activity. Together with decreased expression of the tissue inhibitors of metalloproteinases, this is thought to result in zonal degradation and loss of elastic tissue in the mid-dermis. However, the exact mechanisms leading to the enhanced elastolytic activity in MDE remain elusive. A multifactorial pathogenesis is likely, including genetic predisposition, chronic inflammation, and (auto)immune processes. Moreover, the capacity for elastic fiber renewal appears to be diminished in patients with MDE, limiting regenerative potential and informing possible treatment strategies, for example, by stimulating elastic fiber synthesis. Although the course of MDE is usually benign and asymptomatic, it can cause severe cosmetic problems. Hence, new therapeutic approaches that block increased elastolytic activity and enhance regeneration of elastic tissue observed in MDE patients are required.
... A number of clinical studies has shown some of mesotherapy products promoting fibroblast activation and stimulation of collagen biosynthesis. [19][20][21] However, most of the available data is inconsistent. Another concern is possible complications, among which the most frequently reported are: mycobacterial infection, scarring, formation of hard lumps in the area of injection, lichenoid keratosis, cutaneous necrosis, etc. 22 It is absolutely clear now that there is no perfect universal product or mixture of substances that would guarantee best results with the minimal risk of complications. ...
Article
Full-text available
Aging-related changes of the skin are characterized by reduction of the elasticity, moistness and thickness, appearance of wrinkles, pigmented spots, lentigos, and keratosis. Histological changes include thinning of epidermis, flattening of epidermal-dermal interface, reduction of production and disorganization of collagen and elastin, slowdown of cell turnover, reduction of melanocytes and their erratic activity and the phenomenon of solar elastosis. The objectives of the study were to evaluate the efficacy of mesotherapy with a cocktail containing combination of cell extracts from skin, placenta and mesenchyme with addition of collagen and elastin proteins in rejuvenation and revitalization of the facial skin. The cohort comprised of 26 women in the age 40-65 y.o. (mean age 56 ± 2.5) with Fitzpatrick skin types III and IV and Glogau score II-III. Treatment consisted of mesotherapy applied on the forehead, cheeks, periorbital and perioral areas, chin and neck. The injected formulation was MF+ Mito Organelles™ SPMCE-peptide-extracts from skin, placenta, mesenchyme, with collagen and elastin. Treatment sessions were performed across 12 weeks at weekly intervals. Final results were assessed 1 and 3 months after the last mesotherapy session using photographic comparison and patient's subjective view and external dermatologist-expert's opinion, clinical and instrumental evaluation, and histopathology report. Clinical and histochemical data obtained from the study confirms the anti-aging properties of the used product. Analysis of dermal elastic filaments has proven the reduction of skins roughness and determined the bio-revitalizing and rejuvenating effect of the used product. Study has demonstrated MF+ MO™ SPMCE capacity to promote biosynthesis of new collagen and elastic fibers. The improvements in skin hydration and dramatic reduction of senile lentigo and uneven pigmentation were noted. Obtained data allow to conclude that application of MF+ MO™ SPMCE cellular extracts/peptides in mesotherapy can be considered as safe and effective method of facial rejuvenation.
... Zn-glycine complex is believed to act as anti-ageing agent by preventing ROS formation [8]. Moreover, cream with 0.1% copper-zinc malonate was found to have a positive effect on photoaged facial skin over an eight-week course of treatment, with beneficial results being observed in group of 21 female patients: significant regeneration of skin elastic fibres was observed, leading to wrinkle smoothing [15,30]. ...
Article
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It is well known that zinc ions are widely used in cosmetic products. Their popularity is associated with the multifunctional profile of Zn²⁺, which is classified as an essential chemical element in the human body. This review examines numerous beneficial biological properties of zinc‐containing compounds and classifies the compounds used in cosmetic products according to their functionality profile: antioxidant, sunscreen, anti‐inflammatory, anti‐pigmentation, anti‐aging, anti‐acne, antimicrobial, anti‐odour, cleansing or stabilising activity. It also underlines the significance of zinc in enzymatic processes, which depends on the enzyme type acts as inhibitor or enzymatic stimulator. Moreover, the article describes the chemical nature of the most interesting groups of Zn compounds. This article is protected by copyright. All rights reserved.
... oleic acid and linoleic acid), increased transdermal absorption, allowing active ingredients to penetrate the dermis. The anti-wrinkle activity was the most potent effect observed and was hypothesised to be an effect of vitamin A, amino acids, zinc and copper, which aid in maintaining skin elasticity and structure of the extracellular matrix [144,145], subsequently reducing wrinkle formation and laxity. Zonase enzyme from S. salar egg extract is available in several cosmetic products due to its effective antiaging mechanisms and simple recovery as a waste product from the salmon egg processing industry. ...
Article
The marine environment represents an underexploited resource for the discovery of novel products, despite its high level of biological and chemical diversity. With increasing awareness of the harmful effects of chronic ultraviolet exposure, and a universal desire to improve cosmetic appearance, the market for new cosmetic ingredients is growing, and current trends have generated a greater demand for products sourced from the environment. A growing number of novel molecules from marine flora and fauna exhibit potent and effective dermatological activities. Secondary metabolites isolated from macroalgae, including carotenoids and polyphenols, have demonstrated antioxidant, antiaging and anti-inflammatory activities. In addition, marine extremophilic bacteria have recently been shown to produce bioactive exopolymeric molecules, some of which have been commercialised. Available data on their activities show significant antioxidant, moisturising and antiaging activities, but a more focussed investigation into their mechanisms and applications is required. This review surveys the reported biological activities of an emerging and growing portfolio of marine molecules that show promise in the treatment of cosmetic skin problems including ultraviolet damage, aging and cutaneous dryness.
... A number of clinical studies has shown some of mesotherapy products promoting fibroblast activation and stimulation of collagen biosynthesis. [19][20][21] However, most of the available data is inconsistent. Another concern is possible complications, among which the most frequently reported are: mycobacterial infection, scarring, formation of hard lumps in the area of injection, lichenoid keratosis, cutaneous necrosis, etc. 22 It is absolutely clear now that there is no perfect universal product or mixture of substances that would guarantee best results with the minimal risk of complications. ...
Article
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Aging–related changes of the skin are characterized by reduction of the elasticity, moistness and thickness, appearance of wrinkles, pigmented spots, lentigos, and keratosis. Histological changes include thinning of epidermis, flattening of epidermal-dermal interface, reduction of production and disorganization of collagen and elastin, slowdown of cell turnover, reduction of melanocytes and their erratic activity and the phenomenon of solar elastosis. The objectives of the study were to evaluate the efficacy of mesotherapy with a cocktail containing combination of cell extracts from skin, placenta and mesenchyme with addition of collagen and elastin proteins in rejuvenation and revitalization of the facial skin. The cohort comprised of 26 women in the age 40-65 y.o. (mean age 56 ± 2.5) with Fitzpatrick skin types III and IV and Glogau score II-III. Treatment consisted of mesotherapy applied on the forehead, cheeks, periorbital and perioral areas, chin and neck. The injected formulation was MF+ Mito Organelles™ SPMCE – peptide-extracts from skin, placenta, mesenchyme, with collagen and elastin. Treatment sessions were performed across 12 weeks at weekly intervals. Final results were assessed 1 and 3 months after the last mesotherapy session using photographic comparison and patient’s subjective view and external dermatologist-expert’s opinion, clinical and instrumental evaluation, and histopathology report. Clinical and histochemical data obtained from the study confirms the anti-aging properties of the used product. Analysis of dermal elastic filaments has proven the reduction of skins roughness and determined the bio-revitalizing and rejuvenating effect of the used product. Study has demonstrated MF+ MO™ SPMCE capacity to promote biosynthesis of new collagen and elastic fibers. The improvements in skin hydration and dramatic reduction of senile lentigo and uneven pigmentation were noted. Obtained data allow to conclude that application of MF+ MO™ SPMCE cellular extracts/peptides in mesotherapy can be considered as safe and effective method of facial rejuvenation.
... -Ψευδάργυρος: Το ιχνοστοιχείο αυτό συντελεί στην αναγέννηση των στοιβάδων του δέρµατος, βοηθάει στη σύνθεση του κολλαγόνου και της ελαστίνης, βελτιώνοντας έτσι την αντοχή και την ελαστικότητα. Ο Ψευδάργυρος θεωρείται θεµε-λιώδες στοιχείο για τη σωστή λειτουργία των κυττάρων και η έλλειψή του µπορεί να προκαλέσει αλωπεκία, δερµατίτιδες και προβλήµατα επούλωσης (17). ...
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In this article the beneficial effects for human health of clay minerals is studied. Minerals have been used for medical purposes since Prehistory. The use of medicinal earths in Mesopotamia, Ancient Egypt and Ancient Greece has also been proven. Clay minerals are widely used in spas. They are mixed with water (geotherapy), mixed with sea or salt lake water, or minero-medicinal water and then matured (pelotherapy) or mixed with paraffin (paramuds). Clay minerals are used in Aesthetics and in the Cosmetology to clean and moisturize the skin, to peel off the keratinocytes and to combat compact lipodystrophies, acne and cellulite. Bentonite, kaolinite, illite, montmorillonite and attapulgite are the most known clays used in aesthetic medicine. It is necessary to study the presence of toxic elements as As, Cd, Hg, Pb, etc. in the clay, since these elements, if they are not strongly bounded to the mineral structures, can be exchanged with cations in skin sweat as sodium and be absorbed by the skin. The ratio of aluminum and silicon in the clay and the size of its particles influence the physicochemical, the rheological, and the viscoelastic properties of the clay before and after application on the skin and the biological activity, as well. Maturation procedure affects also on the quality and the effectiveness of the peloid. Innovative methodologies and protocols have been developed for the evaluation of the quality and the influence of muds on human health. Investigations are in progress to qualify peloids for various therapies. Since, these materials are being more-and-more focused on specific pathologies and wellness-relax-spa treatments, it is suggested a Network of specialized laboratories to be set up for the certification of their quality and suitability and the appropriate methodology of application.
... The biosynthesis rate of normal elastin was evaluated by quantifying for newly synthesized tropoelastin, the precursor of elastin. 17,21 Quantitative evaluation of tropoelastin showed minor, but statistically nonsignificant (p= 0.412), increase in the mean level from 13.6±3.5 percent to 14.8±2.9 percent after one month of skin microneedling therapy. ...
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Objective: Treatment of acne scarring is always a challenge. Microneedling therapy or percutaneous collagen induction is a new addition to the treatment modalities for such scars and has been reported to be simple and effective in atrophic acne scar treatment. The aim of this study is to evaluate the clinical effect and objectively quantify the histological changes of acne scarring in response to skin microneedling. Design: A prospective clinical study. Participants: Ten patients with different types of atrophic acne scars were subjected to three months of skin microneedling treatment (six sessions at two-week intervals). Measurements: Patients were photographed, and skin biopsies were obtained at baseline as well as one and three months from the start of treatment. Histometry for epidermal thickness and quantitative evaluation of total elastin; newly synthesized tropoelastin; collagen types I, III, and VII; and newly synthesized collagen were performed for all biopsies. Results: Compared to the baseline, patients' evaluations revealed noticeable clinical improvement in atrophic post-acne scars in response to skin microneedling. There was a statistically significant increase (p<0.05) in the mean of collagen types I, III, and VII and newly synthesized collagen, while total elastin was significantly decreased (p<0.05) after the end of treatment. Conclusions: Multiple minimally invasive sessions of skin microneedling are an effective treatment for post-acne atrophic scars as it stimulates the repair processes with the advantage of being a relatively risk-free, in-office procedure with minimal patient recovery time.
... The biosynthesis rate of normal elastin was evaluated by quantifying for newly synthesized tropoelastin, the precursor of elastin. 17,21 Quantitative evaluation of tropoelastin showed minor, but statistically nonsignificant (p= 0.412), increase in the mean level from 13.6±3.5 percent to 14.8±2.9 percent after one month of skin microneedling therapy. ...
Article
Treatment of acne scarring is always a challenge. Microneedling therapy or percutaneous collagen induction is a new addition to the treatment modalities for such scars and has been reported to be simple and effective in atrophic acne scar treatment. The aim of this study is to evaluate the clinical effect and objectively quantify the histological changes of acne scarring in response to skin microneedling. A prospective clinical study. Ten patients with different types of atrophic acne scars were subjected to three months of skin microneedling treatment (six sessions at two-week intervals). Patients were photographed, and skin biopsies were obtained at baseline as well as one and three months from the start of treatment. Histometry for epidermal thickness and quantitative evaluation of total elastin; newly synthesized tropoelastin; collagen types I, III, and VII; and newly synthesized collagen were performed for all biopsies. Compared to the baseline, patients' evaluations revealed noticeable clinical improvement in atrophic post-acne scars in response to skin microneedling. There was a statistically significant increase (p<0.05) in the mean of collagen types I, III, and VII and newly synthesized collagen, while total elastin was significantly decreased (p<0.05) after the end of treatment. Multiple minimally invasive sessions of skin microneedling are an effective treatment for post-acne atrophic scars as it stimulates the repair processes with the advantage of being a relatively risk-free, in-office procedure with minimal patient recovery time.
... Antiageing. Mahoney et al. [85] evaluated the effects of a bi-metal, 0.1% copper-zinc malonate, containing cream on elastin biosynthesis and elastic tissue accumulation in 21 female patients with photoaged facial skin. After 8 weeks of therapy, significant elastic fiber regeneration was seen in the papillary dermis leading to effacement of wrinkles. ...
Article
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Zinc, both in elemental or in its salt forms, has been used as a therapeutic modality for centuries. Topical preparations like zinc oxide, calamine, or zinc pyrithione have been in use as photoprotecting, soothing agents or as active ingredient of antidandruff shampoos. Its use has expanded manifold over the years for a number of dermatological conditions including infections (leishmaniasis, warts), inflammatory dermatoses (acne vulgaris, rosacea), pigmentary disorders (melasma), and neoplasias (basal cell carcinoma). Although the role of oral zinc is well-established in human zinc deficiency syndromes including acrodermatitis enteropathica, it is only in recent years that importance of zinc as a micronutrient essential for infant growth and development has been recognized. The paper reviews various dermatological uses of zinc.
... As fibras elásticas da derme são responsáveis pela elasticidade fisiológica e resiliência da pele 25 . A degeneração dessas fibras e do colágeno promove a diminuição da 28 , o envelhecimento cronológico das fibras elásticas e a elastose actínica seriam 2 processos distintos. ...
Article
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INTRODUÇÃO: O objetivo deste estudo é avaliar a influência do envelhecimento na qualidade da pele de mulheres brancas, analisando o colágeno, as fibras elásticas e a vascularização. MÉTODO: Foi realizada análise histológica e morfométrica de 218 retalhos pré-auriculares de mulheres brancas, que se submeteram a cirurgia estética facial. Foram utilizados o imunomarcador AntiCD 34, que evidencia os vasos sanguíneos, a coloração de Weigert, para visibilização das fibras elásticas, e a coloração de Picrosirius Ultrared, para analisar e quantificar os colágenos I, III e total. Os dados foram analisados de acordo com a faixa etárias das doadoras: < 40 anos, 40 anos a 49 anos, 50 anos a 59 anos, 60 anos a 69 anos, e > 70 anos. RESULTADOS: Foi observada fragmentação e desorganização das fibras de colágeno, especialmente acima de 60 anos. Não houve diferenças significantes entre a idade e a espessura da derme e da epiderme, porém foi identificada relação com as porcentagens de colágeno I, III e total (P < 0,001). Houve aumento da densidade de fibras elásticas com a progressão da idade (P < 0,001). Comparando-se as peles das pacientes de faixas etárias vizinhas, com diferença de uma década entre elas, não houve diferença significativa na quantidade de material elástico dessas peles; porém, ao se comparar aquelas com diferença de 2 ou mais décadas nas faixas etárias, o aumento foi significante (P < 0,05). A diferença do número de vasos não foi significante (P = 0,112). CONCLUSÕES: O envelhecimento promoveu redução do colágeno, degradação e fragmentação das fibras, e aumento da densidade de material elástico desorganizado, e não influenciou no número de vasos sanguíneos da derme.
... As elastic fibers are responsible for skin resilience, there is need for treatments that might protect existing elastic fibers from premature degradation and facilitate new elastogenesis in skin. Numerous studies have been aimed at reversal of damaged skin (reviewed in Mahoney et al., 2009). We described that a proteolytic digest of elastin (Hinek et al., 2005) and iron (ferric ammonium citrate) (Bunda et al., 2005) can stimulate production of tropoelastin in skin and that polyphenols (tannic acid and ellagic acid; Jimenez et al., 2006) that preferentially bind to elastin protect it from proteolysis. ...
Article
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We have shown that the steroid hormone aldosterone, recognized for its action on the kidney and the cardiovascular system, also modulates deposition of extracellular matrix in human skin. We have shown that treatment of primary cultures of normal skin fibroblasts with aldosterone (10 n-1 μM), in addition to stimulation of collagen type I expression, induces elastin gene expression and elastic fiber deposition. We have further shown that the elastogenic effect of aldosterone, which can be enhanced in the presence of mineralocorticoid receptor (MR) antagonists spironolactone and eplerenone, is executed in a MR-independent manner via amplification of IGF-I receptor-mediated signaling. Because aldosterone applied alone stimulates both collagen and elastin deposition in cultures of fibroblasts and in cultures of skin explants derived from dermal stretch marks, we postulate that this steroid should be used in the treatment of damaged skin that loses its volume and elasticity. Moreover, aldosterone applied in conjunction with spironolactone or eplerenone induces matrix remodeling and exclusively enhances elastogenesis in cultures of fibroblasts and explants derived from dermal scars and keloids. We therefore propose that intra-lesional injection of these factors should be considered in therapy for disfiguring dermal lesions and especially in prevention of their recurrence after surgical excision.
... As elastic fibers are responsible for skin resilience, there is need for treatments that might protect existing elastic fibers from premature degradation and facilitate new elastogenesis in skin. Numerous studies have been aimed at reversal of damaged skin (reviewed in Mahoney et al., 2009). We described that a proteolytic digest of elastin (Hinek et al., 2005) and iron (ferric ammonium citrate) (Bunda et al., 2005) can stimulate production of tropoelastin in skin and that polyphenols (tannic acid and ellagic acid; Jimenez et al., 2006) that preferentially bind to elastin protect it from proteolysis. ...
Article
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We previously demonstrated that aldosterone, which stimulates collagen production through the mineralocorticoid receptor (MR)-dependent pathway, also induces elastogenesis via a parallel MR-independent mechanism involving insulin-like growth factor-I receptor (IGF-IR) signaling. The present study provides a more detailed explanation of this signaling pathway. Our data demonstrate that small interfering RNA-driven elimination of MR in cardiac fibroblasts does not inhibit aldosterone-induced IGF-IR phosphorylation and subsequent increase in elastin production. These results exclude the involvement of the MR in aldosterone-induced increases in elastin production. Results of further experiments aimed at identifying the upstream signaling component(s) that might be activated by aldosterone also eliminate the putative involvement of pertussis toxin-sensitive Gαi proteins, which have previously been shown to be responsible for some MR-independent effects of aldosterone. Instead, we found that small interfering RNA-dependent elimination of another heterotrimeric G protein, Gα13, eliminates aldosterone-induced elastogenesis. We further demonstrate that aldosterone first engages Gα13 and then promotes its transient interaction with c-Src, which constitutes a prerequisite step for aldosterone-dependent activation of the IGF-IR and propagation of consecutive downstream elastogenic signaling involving phosphatidylinositol 3-kinase/Akt. In summary, the data we present reveal new details of an MR-independent cellular signaling pathway through which aldosterone stimulates elastogenesis in human cardiac fibroblasts.
Article
Purpose: To review and summarize studies on the anatomy and involutional changes of the midface. Methods: A PubMed search was performed searching for studies on the anatomy and involutional changes concerning the midface. Results: The anatomy of the midface is complex. Studies of involutional change vary in scientific quality and have conflicting results. However, it appears that among the more common changes, there is a decrease in the maxillary and pyriform angle, with changes to the orbital floor position. Further, there appears to be an inferior migration of the fat compartments of the midface during aging, exacerbating the hollow of the palpebromalar groove and causing a deepening of the nasojugal groove. Changes to the volume of the buccal extension of the buccal fat pad exacerbate these changes and contribute to the gestalt changes associated with facial aging. Here, we review the major characteristics of soft tissue and bony changes on the midface, with special reference to their anatomic relationships. Conclusions: The major findings characterizing midface aging are related largely to the soft tissue. However, more robust studies are required to quantify these changes and to appraise their impact on the overall manifestation of aging.
Presentation
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The skin is the largest organ of the body that protects our internal tissues from chemical, physical, and microbial damage. It also helps to prevent loss of water and other endogenous substances, participates in thermoregulation of the body and serves as an excretory organ. With age, the skin undergoes vast changes, becoming wrinkled and rigid, losing its firmness, elasticity, tone, texture, thickness, flexibility and moisture content Skin aging is attributed to several changes. These include alterations in the dermal extracellular matrix (ECM) made up mainly by collagen (which provides strength and structure) and elastin (which provides elasticity and resilience) fibres. The biocidal properties of copper are known for ages. In addition to that copper is involved in numerous physiological and metabolic processes critical for the appropriate functioning of almost all tissues in the human body. In the skin, copper is involved in the synthesis and stabilization of extracellular matrix skin proteins and angiogenesis. In the skin, pathophysiology of copper involved to a) stimulates dermal fibroblasts proliferation; b) upregulates collagen (types I, II, and V) and elastin fiber components (elastin, fibrillins) production by fibroblasts, seemingly through the induction of TGF-β; c) stimulates HSp-47, essential to collagen fibril formation; d) serves as a cofactor of LOX needed for efficient ECM protein cross-linking; e) stabilizes the skin ECM once formed, as increased crosslinking of collagen and elastin matrices occurs in a copper dose dependant manner; f) serves as a cofactor of superoxide dismutase, an antioxidant enzyme present in the skin, important for protection against free radicals; g) inhibits cellular oxidative effects such as membrane damage and lipid peroxidation; and h) serves as a cofactor of tyrosinase, a melanin biosynthesis essential enzyme responsible for skin and hair pigmentation.
Chapter
A detailed appreciation of the development, structure and function of human skin is fundamental to understanding diseases that originate in or target the skin. Recent advances in molecular science have provided fascinating new insights into stem cell biology and skin homeostasis as well as disease processes such as inflammation, wound healing, ageing and neoplasia, providing novel opportunities to improve the diagnosis and therapy of skin diseases.
Conference Paper
Article
Ethnopharmacological relevance: Sorocea guilleminina Gaudich. is a tree or shrub endemic to Brazil. Its leaves are used in Brazilian folk medicine for the healing of wounds, stomach problems, inflammation and as diuretic. The present study evaluates the activity and action mechanisms of the healing properties of the aqueous extract of S. guilleminiana leaves (AESg), in experimental models in vivo and in vitro, as well as performs a phytochemical analysis of the extract. Materials and methods: The AESg was prepared by infusion: Ten g of dry leaves powder in 1 L hot water, soaked for 15 min, filtered, lyophilized, and stored at -30 °C. Phytochemical analyses were realized by colorimetry and HPLC/ESI/MS. Its' in vitro cytotoxicity was evaluated on fibroblastic N3T3 cells. The potential of the wound healing activity in vivo was evaluated using excision and incision wound rat models, by histopathology of the injured skin along with the determination of nitric oxide, cytokines (IL-1β, IL-10, and TNF-α), and antioxidant parameters (GSH, MPO and CAT). In vitro wound healing activity was also demonstrated in scratched N3T3 cells, by measuring the proliferation/migration rate. Results: The phytochemical analysis of the AESg revealed a strong presence of polar compounds, especially flavonoids (4 majoritarian), as well as terpenes and/or sterols (2 majoritarian). The AESg showed no toxicity in the N3T3 cell line (IC50 > 800 μg/mL). Topical treatment with the AESg showed an increase (p < 0.05) in wound contraction with 2 mg/g cream on days 5 and 9 (43.56% and 6.70% increase, respectively), and with 50 mg/g on days 7 and 9 (10.88% and 7.91%, respectively), compared to the vehicle (non-ionic neutral cream). Topical application of AESg (2 or 50 mg/g non-ionic cream) in incised wounds caused an increase in the force necessary for the rupture of the wound when compared to the vehicle group. No changes in cytokines (IL-1β, IL-10, or TNF-α) or NO accumulation was found with up to 50 mg/g AESg treatment. For antioxidant activity on the incision wound, an increase in GSH levels was denoted with the AESg use, at the lowest and highest dose (2 and 50 mg/g) by 75.86% and 61.20% respectively, when compared to the vehicle. Also, the CAT activity was accentuated by AESg at the highest dose (50 mg/g) by 85.87%. Finally, the AESg at all doses attenuated MPO activity significantly in the incision wound by 71.35%, 73.21%, 78.08%, respectively. In the scratch test on N3T3 cells, the treatment with AESg resulted also in an increase in fibroblast proliferation/migration rate, compared to the vehicle. Conclusion: AESg is not cytotoxic. The results confirm the popular use of the leaf infusion of S. guilleminiana for the treatment of cutaneous wounds, possibly by stimulating the proliferation of fibroblasts with a consequent deposition of collagen, fastening rearrangement of collagen fibers, and greater transformation into myofibroblasts, essential in the healing process. Preliminary chemical analyzes of AESg revealed the presence mainly of phenolic compounds, being salicylic acid, gallic acid, pinocembrin and isoquercitrin the majoritarian ones.
Article
A hyaluronic acid (HAc) - hydroxyapatite (HAp) nanocomposite (HAc-nanoHAp) hydrogel was fabricated through an in situ precipitation process for mechanical and biological enhancement as a soft tissue augmentation product. In this study, these composite hydrogel fillers were analyzed from three different perspectives and compared with pure HAc hydrogel for soft tissue augmentation application: 1) rheological behaviors, 2) in vivo lateral diffusion under mouse skin, and 3) wrinkle improvement in a photo-aged mouse model. HAc-nanoHAp provided great improvement to wrinkles because of its higher stiffness and gel cohesiveness in comparison with that of pure HAc. HAc-nanoHAp also presented great enhancement in strengthening the dermal matrix by stimulating the synthesis of collagen and elastin. Thus, HAc-nanoHAp filler has great potential as a soft tissue augmentation product, improving the biophysical and biological performance in skin tissue. This article is protected by copyright. All rights reserved.
Chapter
Aging of the skin is a multifactorial phenomenon, in which ongoing intrinsic changes combine the cumulative effects of chronic exposure to the elements, primarily ultraviolet radiation, in a synergistic fashion, causing decreased skin thickness and elasticity with subsequent wrinkle formation. Understanding the mechanisms by which the skin ages has been increasing significantly, along with considerable progress on the way to prevent and reverse the visible signs of aging. However, there are still several mysterious factors concerning the aging process and why we all appear to age differently. The skin is mostly important because of its social impact and as it is visible, making it an appropriate model for studying the aging phenomenon. As the skin ages, multiple histological changes occur throughout the epidermis, dermis, and subcutaneous tissue which manifest via distinct skin alterations in appearance. There is general agreement that cutaneous aging is a complex biological process, which affects various layers of the skin; however, the major changes are seen in the dermis. This chapter discusses the main histological and immunohistochemical changes observed in aging skin.
Chapter
Aging of the skin is a multifactorial phenomenon, in which ongoing intrinsic changes combine the cumulative effects of chronic exposure to the elements, primarily ultraviolet radiation, in a synergistic fashion, causing decreased skin thickness and elasticity with subsequent wrinkle formation. Understanding the mechanisms by which the skin ages has been increasing significantly, along with considerable progress on the way to prevent and reverse the visible signs of aging. However, there are still several mysterious factors concerning the aging process and why we all appear to age differently. The skin is mostly important because of its social impact and as it is visible, making it an appropriate model for studying the aging phenomenon. As the skin ages, multiple histological changes occur throughout the epidermis, dermis, and subcutaneous tissue which manifest via distinct skin alterations in appearance. There is general agreement that cutaneous aging is a complex biological process, which affects various layers of the skin; however, the major changes are seen in the dermis. This chapter discusses the main histological and immunohistochemical changes observed in aging skin.
Article
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In the early 1990s, the biological significance of light-emitting diodes was realized. Since this discovery, various light sources have been investigated for their cutaneous effects. A Medline search was performed on light-emitting diode lights and their therapeutic effects between 1996 and 2010. Additionally, an open-label, investigator-blinded study was performed using a yellow light-emitting diode device to treat acne, rosacea, photoaging, alopecia areata, and androgenetic alopecia. The authors identified several case-based reports, small case series, and a few randomized controlled trials evaluating the use of four different wavelengths of light-emitting diodes. These devices were classified as red, blue, yellow, or infrared, and covered a wide range of clinical applications. The 21 patients the authors treated had mixed results regarding patient satisfaction and pre- and post-treatment evaluation of improvement in clinical appearance. Review of the literature revealed that differing wavelengths of light-emitting diode devices have many beneficial effects, including wound healing, acne treatment, sunburn prevention, phototherapy for facial rhytides, and skin rejuvenation. The authors' clinical experience with a specific yellow light-emitting diode device was mixed, depending on the condition being treated, and was likely influenced by the device parameters.
Book
This book describes mechanisms of skin damage generation and examines the potential impact of free radicals, reactive oxygen species (ROS) and oxidative damage on the skin aging process. It also evaluates methods to decrease skin oxidative stress, oxidative damage, and skin aging. The identification of free radical reactions as promoters of the skin aging process implies that interventions aimed at limiting or inhibiting free radical reactions should be able to reduce the rate of formation of aging-related changes with a consequent reduction of the aging rate. This book highlights how aging of the skin happens, as well as what are the causes and the best ways to prevent and treat it.
Article
Background Wrinkles are associated with cutaneous aging especially on sun-exposed skin. Despite they are considered a major topic in cosmetic dermatology, very few reports have studied the specific histological and immunohistochemical changes characteristic for wrinkles.AimThe study aims to evaluate the histological and immunohistochemical changes of static forehead wrinkles in relation to surrounding photoaged skin.Methods Biopsy specimens were obtained from the forehead wrinkles of 20 volunteers of Glogau's class III–IV wrinkles. Using histological and immunostaining methods coupled with computerized morphometric analysis, measurement of epidermal thickness and quantitative evaluation of total elastin and tropoelastin as well as collagen types I, III, and VII were performed for skin biopsies.ResultsIn the wrinkle site, there was statistically significant lower epidermal thickness (P = 0.001), elastin (P < 0.001), tropoelastin (P < 0.001), and collagen VII (P < 0.001) than the surrounding photoaged skin. Meanwhile, there was no significant difference between the wrinkle site and adjacent photoaged skin regarding collagen type I (P = 0.07) or III (P = 0.07).Conclusion This study detected some histological and immunohistochemical differences in the wrinkle site when compared to adjacent photoaged skin. This may help in understanding the pathophysiology of facial wrinkling as well as its ideal way of management.
Article
Microneedling or percutaneous collagen induction is a new modality used for skin rejuvenation, tightening, and scar remodeling. It offers a simple and effective treatment for photoaged skin with minimal disruption of the epidermis, thus limiting adverse effects and minimizing downtime. To evaluate the efficacy, coupled with quantitative assessment, of the histological changes in response to multiple sessions of skin microneedling in the treatment of aging skin. Ten patients with Fitzpatrick skin type III and IV and Glogau class II to III wrinkles were subjected to six skin microneedling sessions at 2-week intervals. Standard photographs and skin biopsy specimens were obtained at baseline and at one and three months after the start of treatment. Histometry for epidermal thickness and quantitative evaluation of collagen types I, III, and VII, newly synthesized collagen, total elastin, and tropoelastin were performed for all skin biopsies. Skin microneedling produced noticeable clinical improvement of photoaged skin, with corresponding histological enhancement. Compared to the baseline, collagen types I, III, and VII, as well as newly synthesized collagen, together with tropoelastin showed a statistically significant increase (P < 0.05) in response to treatment, while the mean level of total elastin was significantly decreased (P < 0.05) after treatment. Skin microneedling is a promising minimally invasive treatment option with the advantage of increased collagen production. However, multiple sessions are usually needed to maintain the improvement achieved. © 2015 The International Society of Dermatology.
Article
Photoaging skin is due to accumulative effect of UV irradiation that mainly imposes its damage on dermal fibroblasts. To mimic the specific cellular responses invoked by long term effect of UVB, it is preferable to develop a photo-damaged model in vitro based on repeated UVB exposure instead of a single exposure. To develop a photo-damaged model of fibroblasts by repeated UVB exposure allowing for investigation of molecular mechanism underlying premature senescence and testing of potential anti-photoaging compounds. Mouse dermal fibroblasts (MDFs) at early passages (passages 1-3) were exposed to a series of 4 sub-cytotoxic dose of UVB. The senescent phenotypes were detected at 24 or 48h after the last irradiation including cell viability, ROS generation, mitochondrial membrane potential, cell cycle, production and degradation of extracellular matrix. Repeated exposure of UVB resulted in remarkable features of senescence. It effectively avoided the disadvantages of single dose such as induction of cell death rather than senescence, inadequate stress resulting in cellular self-rehabilitation. Our work confirms the possibility of detecting cellular machinery that mediates UVB damage to fibroblasts in vitro by repeated exposure, while the potential molecular mechanisms including cell surface receptors, protein kinase signal transduction pathways, and transcription factors remain to be further evaluated.
Article
Objective: There is an increasing demand for scientifically documented over-the-counter products on the cosmetic market. Salmon eggs are rich in proteins, vitamins and minerals with anti-oxidative and anti-inflammatory properties, as well as free amino acids and lipids documented to be beneficial for skin. Of the fatty acids, several are commonly used as skin penetration enhancers. The unique combination of active substances led us to study whether an extract from salmon eggs could serve as an ingredient for skin care. Methods: We conducted a double-blinded, randomized clinical trial with 66 healthy female volunteers. Efficacy of the salmon egg extract was evaluated at concentrations of 1% and 5% in vehicle formulation, and responses after 7, 14, 28 and 56 days of treatment were compared with baseline. Composition of the extract was analysed to improve the understanding of the effects of the extract on skin. The salmon egg extract was safety-tested by repeat insult patch test. Results: Treatment of facial skin with the salmon egg extract significantly improved all parameters investigated, wrinkles, pigmentation, redness, brightness and hydration and led to global improvement of the facial skin. Efficacy of the extract was dose dependent and time dependent. There were no adverse reactions noted during the course of the repeat insult patch test, demonstrating that the extract causes neither skin irritation nor sensitization. Furthermore, chemical analyses of the extract revealed the composition of a vast number of active substances, including unsaturated fatty acids, vitamins, proteins, minerals, DNA and RNA. Conclusion: The salmon egg extract serves as a skin care ingredient that significantly improves characteristics important for perception of skin ageing and health. The efficacy of the treatment is conceivably accounted for by the unique combination of numerous active substances present in the salmon egg extract.
Article
Cutaneous aging is a complex biological process in which alterations resulting from both innate aging and photodamage are superimposed in the sun-exposed areas of skin. Profound changes have been demonstrated in the dermal connective tissues, among them the elastic fibers that provide physiologic properties of elasticity and resilience to the normal skin. In innate aging there is loss of elastic fibers, while in sun-damaged skin there is massive accumulation of elastotic material that has, however, lost the functional elastic properties. As a result of these changes, combined with other extracellular matrix alterations, skin becomes loose and sags with loss of recoil with advancing age. A bimetal, 0.1% copper-zinc malonate-containing cream (ELASTIderm™, Obagi Medical Products), has recently been shown to improve the appearance of sun-damaged facial skin when applied twice daily for up to 6-8 weeks. This improvement was accompanied by repair of the elastic fiber network. While the precise mechanisms of these regenerative processes are not clear at present, this compound appears to lead to clinical improvement through its effects on the expression of the elastin gene in the dermis.
Article
Background: Laser is one of the main tools for skin resurfacing. Erbium:yttrium-aluminum-garnet (Er:YAG) was the second ablative laser, after carbon dioxide, emitting wavelength of 2940 nm. Fractional laser resurfacing has been developed to overcome the drawbacks of ablative lasers. Objective: We aimed to objectively evaluate the histopathological and immunohistochemical effects of Er:YAG 2940-nm laser for facial rejuvenation (multiple sessions of fractional vs single session of ablative Er:YAG laser). Methods: Facial resurfacing with single-session ablative Er:YAG laser was performed on 6 volunteers. Another 6 were resurfaced using fractional Er:YAG laser (4 sessions). Histopathological (hematoxylin-eosin, orcein, Masson trichrome, and picrosirius red stains) and immunohistochemical assessment for skin biopsy specimens were done before laser resurfacing and after 1 and 6 months. Histometry for epidermal thickness and quantitative assessment for neocollagen formation; collagen I, III, and VII; elastin; and tropoelastin were done for all skin biopsy specimens. Results: Both lasers resulted in increased epidermal thickness. Dermal collagen showed increased neocollagen formation with increased concentration of collagen types I, III, and VII. Dermal elastic tissue studies revealed decreased elastin whereas tropoelastin concentration increased after laser resurfacing. Neither laser showed significant difference between their effects clinically and on dermal collagen. Changes in epidermal thickness, elastin, and tropoelastin were significantly more marked after ablative laser. Limitations: The small number of patients is a limitation, yet the results show significant improvement. Conclusion: Multiple sessions of fractional laser have comparable effects to a single session of ablative Er:YAG laser on dermal collagen but ablative laser has more effect on elastic tissue and epidermis.
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Severe structural changes, including deterioration of the mechanical properties of the dermis, occur during skin aging. It is well known that the degradation of the extracellular matrix contributes to the physical changes in aged skin. Whereas many studies have been devoted to age-related alterations of collagen fibrils, far less attention has been paid to another major family of extracellular matrix components, the glycosaminoglycans (GAGs) and proteoglycans (PGs). Heparan sulphate-proteoglycans, (HS-PGs), a subclass of the PG family that decreases during aging, regulate proliferation and proteolysis as well as matrix adhesion and assembly, and thus, may have important functions in skin. These PGs may represent important targets for dermo-cosmetology in fighting skin aging. The purpose of this study was to demonstrate the potential of a new C-xylopyranoside derivative (C-beta-D-xylopyranoside-2-hydroxy-propane simplified as C-Xyloside) to improve HS-PGs expression in human skin. In an organotypical model of corticosteroid atrophic human skin, characterized by a decrease of PGs expression, treatment with C-Xyloside improved expression of HS-PGs.
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• L-Ascorbic acid stimulates procollagen synthesis in cultured human skin fibroblasts without appreciably altering noncollagen protein synthesis. The effect is unrelated to intracellular degradation of newly synthesized procollagen. Levels of mRNA for pro α1(I), pro α2(I), and pro α1(III), measured by hybridization with the corresponding cDNA probes, are elevated in the presence of ascorbic acid, whereas the level of mRNA for fibronectin is unchanged. Levels of functional mRNA for procollagen, measured in a cell-free translation assay, are specifically increased in the presence of ascorbic acid. Thus, ascorbic acid appears to control the expression of three different procollagen genes, each of which is located on a separate chromosome. It is proposed that intracellularly accumulated procollagen in ascorbate deficiency may lead to a translational repression of procollagen synthesis. Ascorbic acid may relieve this block by promoting hydroxyproline formation and, consequently, secretion of procollagen from the cell. The increased level of procollagen mRNA under the influence of ascorbic acid may be secondary to increased synthesis of procollagen polypeptides; the control point may be gene transcription or mRNA degradation. (Arch Dermatol 1987;123:1684-1686)
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Recently, there has been an exponential increase in the use of alpha-hydroxy acids in dermatologic practice. Their inclusion in a myriad of cosmetic preparations underscores their popularity. Among the clinical effects of alpha-hydroxy acids are their ability to prevent the atropy resulting from potent topical corticosteroids, improve the appearance of photoaged skin, and correct disorders of keratinization. Despite this range of desirable effects, very little is known about the specific changes produced by various alpha-hydroxy acid preparations in the epidermis and dermal extracellular matrix. Previous work by others has demonstrated the ability of another alpha-hydroxy acid to increase viable epidermal thickness, and dermal glycosaminoglycans. In this study, we examined the effect of 20% citric acid lotion, as compared with vehicle alone, on skin thickness, viable epidermal thickness, and dermal glycosaminoglycan content. Biopsy samples were harvested after 3 months of treatment. Image analysis of biopsy sections revealed increases in viable epidermal thickness and dermal glycosaminoglycans in treated skin. Topical citric acid produces changes similar to those observed in response to glycolic acid, ammonium lactate, and retinoic acid including increases in epidermal and dermal glycosaminoglycans and viable epidermal thickness. Further studies of citric acid and other alpha-hydroxy acids are warranted to clarify their clinical effects and mechanisms of action.
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Long-term exposure to ultraviolet irradiation from sunlight causes premature skin aging (photoaging), characterized in part by wrinkles, altered pigmentation, and loss of skin tone. Photoaged skin displays prominent alterations in the collagenous extracellular matrix of connective tissue. We investigated the role of matrix-degrading metalloproteinases, a family of proteolytic enzymes, as mediators of collagen damage in photoaging. We studied 59 whites (33 men and 26 women, ranging in age from 21 to 58 years) with light-to-moderate skin pigmentation, none of whom had current or prior skin disease. Only some of the participants were included in each of the studies. We irradiated their buttock skin with fluorescent ultraviolet lights under standard conditions and obtained skin samples from irradiated and nonirradiated areas by keratome or punch biopsy. In some studies, tretinoin and its vehicle were applied to skin under occlusion 48 hours before ultraviolet irradiation. The expression of matrix metalloproteinases was determined by in situ hybridization, immunohistology, and in situ zymography. Irradiation-induced degradation of skin collagen was measured by radioimmunoassay of soluble cross-linked telopeptides. The protein level of tissue inhibitor of matrix metalloproteinases type 1 was determined by Western blot analysis. A single exposure to ultraviolet irradiation increased the expression of three matrix metalloproteinases -- collagenase, a 92-kd gelatinase, and stromelysin -- in skin connective tissue and outer skin layers, as compared with nonirradiated skin. The degradation of endogenous type I collagen fibrils was increased by 58 percent in irradiated skin, as compared with nonirradiated skin. Collagenase and gelatinase activity remained maximally elevated (4.4 and 2.3 times, respectively) for seven days with four exposures to ultraviolet irradiation, delivered at two-day intervals, as compared with base-line levels. Pretreatment of skin with tretinoin (all-trans-retinoic acid) inhibited the induction of matrix metalloproteinase proteins and activity (by 70 to 80 percent) in both connective tissue and outer layers of irradiated skin. Ultraviolet irradiation also induced tissue inhibitor of matrix metalloproteinases-1, which regulates the enzyme. Induction of the inhibitor was not affected by tretinoin. Multiple exposures to ultraviolet irradiation lead to sustained elevations of matrix metalloproteinases that degrade skin collagen and may contribute to photoaging. Treatment with topical tretinoin inhibits irradiation-induced matrix metalloproteinases but not their endogenous inhibitor.
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Solar UV radiation damages human skin, affecting skin tone and resiliency and leading to premature aging (photoaging), the symptoms of which include leathery texture, wrinkles, mottled pigmentation, laxity and sallowness. We propose that photoaging results largely from UV induction of matrix metalloproteinases (MMP) that degrade skin collagen. We find that pretreatment of human skin with all-trans retinoic acid (tRA) inhibits UV induction of MMP, suggesting that tRA can protect against UV-induced collagen destruction and may therefore be able to lessen the effects of photoaging. The tRA prevents UV-induced accumulation of c-Jun protein, which is required for MMP gene expression. Activation of c-Jun transcriptional activity requires N-terminal phosphorylation. The majority of c-Jun in human skin in vivo is N-terminal phosphorylated. Topically applied tRA does not inhibit N-terminal phosphorylation by UV-induced c-Jun kinase activity in human skin. The tRA likely acts to reduce UV induction of c-Jun protein by stimulating its breakdown through the ubiquitin-proteasome pathway.
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Lipoid proteinosis (OMIM 247100), also known as Urbach-Wiethe disease or hyalinosis cutis et mucosae, is a rare autosomal recessive disorder characterized by generalized thickening and scarring of the skin and mucosae. In 2002, the disorder was mapped to a locus on chromosome 1q21 and pathogenic mutations were identified in the ECM1 gene, which encodes for the glycoprotein extracellular matrix protein 1 (ECM1). ECM1 has since been shown to have several important biological functions. It has a role in the structural organization of the dermis (binding to perlecan, matrix metalloproteinase-9 and fibulin) as well as being targeted as an autoantigen in the acquired disease lichen sclerosus. ECM1 also shows over-expression in certain malignancies and is abnormally expressed in chronologically aged and photo-aged skin. Thus far, 26 different inherited mutations in ECM1 have been reported in lipoid proteinosis. In this article, we provide an update on the molecular pathology of lipoid proteinosis, including the addition of 15 new mutations in ECM1 to the mutation database, and review the biological functions of the ECM1 protein in health and disease.
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In clinical studies, the formation of facial wrinkles has been closely linked to the loss of elastic properties of the skin. Cumulative irradiation with ultraviolet (UV) B at suberythemal doses significantly reduces the elastic properties of the skin, resulting in the formation of wrinkles. In in vitro studies, we identified a paracrine pathway between keratinocytes and fibroblasts, which leads to wrinkle formation via the up-regulation of fibroblast elastases that degrade elastic fibers. UVB irradiation stimulates the activity of fibroblast elastases in animal skin. Scanning electron microscopy revealed that cumulative UVB irradiation elicits a marked alteration in the three-dimensional structure of elastic fibers, which is closely associated with the subsequent reduction in the elastic properties of the skin, resulting in wrinkle formation. Studies using anti-wrinkle treatments suggest a close relationship between the recovery of wrinkles and an improvement in the linearity of elastic fibers. Those studies also suggest a close correlation between the recovery in the linearity of elastic fibers and the improvement in skin elasticity. In a study using ovariectomized animals, we characterized the important role of elastase in their high vulnerability to UV-induced wrinkle formation. A synthetic inhibitor specific for fibroblast elastases significantly prevents wrinkle formation without reducing the elastic properties of the skin, accompanied by minor damage in elastic fibers. Finally, we identified an effective extract of Zingiber officinale (L.) Rose from a screen of many herb extracts, which has a safe and potent inhibitory activity against fibroblast elastases. Animal studies using the L. Rose extract revealed that it has significant preventive effects against UVB-induced wrinkle formation, which occur in concert with beneficial effects on skin elasticity. A 1-year clinical study on human facial skin to determine the efficacy of the L. Rose extract demonstrated that it inhibits the UV-induced decrease in skin elasticity and prevents or improves wrinkle formation in skin around the corner of the eye without changing the water content of the stratum corneum. Our long-term studies support our hypothesis for a mechanism of wrinkle formation in which cytokine expression is activated by UV irradiation and triggers dermal fibroblasts to increase the expression of elastase. That increase in elastase results in the deterioration of the three-dimensional architecture of elastic fibers, reducing skin elasticity and finally leading to the formation of wrinkles.