No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Effects of vitamin C on dark circles of the lower eyelids: Quantitative evaluation using image analysis and echogram
Skin Research and Technology
Abstract
The pathogenesis of dark circles of the lower eyelid (DCLE) has been considered to involve stasis and hyperpigmentation of the eyelids. We have already reported that dermal thickness of lower eyelid skin may represent another factor that affects the appearance of DCLE. The aim of this study was to evaluate the efficacy of vitamin C, which is known to increase collagen, on DCLE through a clinical trial.
Fourteen subjects with DCLE applied either 10% sodium ascorbate (ANa) or ascorbic acid glucoside (AG) lotion in split-face fashion (opposite side: vehicle only) for 6 months. Melanin index (MI), erythema index (EI), thickness and echogenicity of the dermis at bilateral lower eyelids was measured during this trial.
Change in EI was significantly smaller on the ANa-treated side than on the vehicle-treated side. Dermal thickness tended to be thicker for the ANa-treated side than for the vehicle-treated side, although no significant difference was seen. Both EI and dermal thickness tended to change in parallel manner. On the other hand, no significant differences in changes of EI, MI, and dermal thickness were found between AG- and vehicle-treated sides.
ANa may improve DCLE by thickening the eyelid dermis and concealing dark coloration due to congested blood.
... By initiating oxidative stress, compromising cell membrane integrity, producing toxic byproducts, and promoting inflammation ROS oxidize membrane phospholipids, causing lipid peroxidation and unsaturated lipid chains to form hydroperoxidised lipids and alkyl radicals, affecting membrane structure, fluidity, and lipoperoxidation. (Hussen et al., 2024b;Rhie et al., 2001;Irato and Santovito, 2021) Melanogenesis ROS imbalance can affect melanin production, leading to pigmentation disorders UV-induced ROS and RNS can stimulate skin melanogenesis, a melanin production process, leading to dermatological issues like melasma, hyperpigmentation, and actinic lentigo due to abnormal melanin production (Uwa, 2017;Ö zkan et al., 2005;Darvin et al., 2006;Rattanawiwatpong et al., 2020;Glynn et al., 2007;Kamei et al., 2009;Trela-Makowej et al., 2022) Skin Matrix ROS promote the breakdown of collagen and elastin in the dermis ROS trigger growth factors and cytokines, causing collagen degradation and inflammatory cytokines, attracting neutrophils, monocytes, and macrophages, contributing to skin aging and increased ROS production (Pinnell, 2003;Santos et al., 2021;Al-Niaimi and Chiang, 2017;Ohshima et al., 2009;Chambial et al., 2013;Ernster and Dallner, 1995;Aaseth et al., 2021;Ayunin et al., 2022;Mortensen et al., 1997;Du et al., 2017) olive or light brown. Type V is brown skin that rarely burns and tans profusely (D'Orazio et al., 2013). ...
... In addition, ROS trigger the activation of c-Jun N-terminal kinase (JNK) following UV exposure, which stimulates the production of MMP-1. ROS cause persistent phosphorylation of the epidermal growth factor receptor by blocking protein tyrosine phosphatase, which activates JNK (Ohshima et al., 2009). An in vivo study has shown that the accumulation of hydrogen peroxide (H₂O₂) in the skin, due to decreased catalase activity, directly enhances MMP-1 expression (Chambial et al., 2013). ...
... It also alters the equilibrium between ferric iron (Fe³⁺) and ferrous iron (Fe 2 ⁺), scavenges oxygen, and inhibits oxidation (Santos et al., 2021;Al-Niaimi and Chiang, 2017). The decline in ascorbate levels associated with aging is complex and involves multiple cellular signaling pathways, including increased turnover, higher utilization, reduced cellular uptake, and decreased absorption/reabsorption (Ohshima et al., 2009). Additionally, ascorbic acid may provide prevention of cancer. ...
... Thiamine hydrochloride (B 1 .HCl) is used in the food industry as a nutritional additive, nutritional source and flavour enhancer. Hydrochloride form of pyridoxine, pyridoxine hydrochloride (B 6 .HCl) functions to treat number of disorders. It is mainly used as dietary supplement and for the enrichment of cereals, flour, rice, confectionery and dry food preparations. ...
... Important parameters such as partial molar volumes and viscosities are known to provide useful insight into solution structure and interactions. As vitamins are biologically important their biomedical properties are most commonly investigated [2][3][4][5][6][7]. Some data have been reported on structural, crystallographic, spectrophotometric, spectrofluorimetric, spectrothermodynamic and nanoscale properties of B 1 .HCl, B 6 . ...
... As vitamins are biologically important their biomedical properties are most commonly investigated [2][3][4][5][6][7]. Some data have been reported on structural, crystallographic, spectrophotometric, spectrofluorimetric, spectrothermodynamic and nanoscale properties of B 1 .HCl, B 6 . HCl and NaAs [1,[8][9][10][11][12][13]. Despite their fundamental importance the volumetric and viscometric values for aqueous solutions of these vitamins are limited. ...
This paper presents data for density and relative viscosity measurements of aqueous solutions of thiamine hydrochloride, pyridoxine hydrochloride and sodium-L-ascorbate in dilute solutions (0-0.1) mol⋅kg⁻¹ at three different temperatures, T = (275.15, 277.15 and 279.15) K and at 101.3 kPa. Density results have been used to calculate apparent molar volume of solute , limiting apparent molar volume of solute , limiting apparent molar expansivity of solute , and coefficient of thermal expansion . Calculated viscosity values have been correlated according to Jones-Dole equation to obtain Falkenhagen coefficient A, Jones-Dole viscosity B-coefficient, temperature derivative of B-coefficient i.e. and hydration number . Free energy of activation for viscous flow per mole of solvent , per mole of solute entropy of activation per mole of viscous flow of solution and enthalpy of activation have also been computed through B-coefficient. These significant parameters have been discussed in terms of different molecular interactions.
... Reduces ROS [84] Acts as a cofactor in the biosynthesis of procollagen and elastin [85] Induces collagen synthesis in human skin fibroblasts and increase dermal thickness [86,87] Application of 5% ascorbic acid for 6 months led to a clinical improvement of the photodamaged skin [88]. ...
... In the skin, ascorbic acid is a cofactor required for the synthesis of procollagen and elastin [85]. Ex vivo and in vivo studies suggest that ascorbic acid induces collagen synthesis in human skin fibroblasts, and increases dermal thickness (Table 2) [86,87]. Topical formulations containing ascorbic acid have clinical efficacy in antiaging treatments (Table 2) [71,88,118]. ...
The dermis is primarily composed of the extracellular matrix (ECM) and fibroblasts. During the aging process, the dermis undergoes significant changes. Collagen, which is a major component of ECM, becomes fragmented and coarsely distributed, and its total amount decreases. This is mainly due to increased activity of matrix metalloproteinases, and impaired transforming growth factor-β signaling induced by reactive oxygen species generated during aging. The reduction in the amount of collagen hinders the mechanical interaction between fibroblasts and the ECM, and consequently leads to the deterioration of fibroblast function and further decrease in the amount of dermal collagen. Other ECM components, including elastic fibers, glycosaminglycans (GAGs), and proteoglycans (PGs), also change during aging, ultimately leading to a reduction in the amount of functional components. Elastic fibers decrease in intrinsically aged skin, but accumulate abnormally in photoaged skin. The changes in the levels of GAGs and PGs are highly diverse, and previous studies have reported conflicting results. A reduction in the levels of functional dermal components results in the emergence of clinical aging features, such as wrinkles and reduced elasticity. Various antiaging approaches, including topicals, energy-based procedures, and dermal fillers, can restore the molecular features of dermal aging with clinical efficacy. This review summarizes the current understanding of skin aging at the molecular level, and associated treatments, to put some of the new antiaging technology that has emerged in this rapidly expanding field into molecular context.
... Vitamin C promotes collagen production and conceals color of blood stasis, which could improve appearance of dark circles under the lower eye lid. 34 Ohshima et al 34 showed that vitamin C and its derivatives, such as magnesium ascorbyl phosphate and ascorbic acid glucoside, inhibit melanogenesis in human melanocytes. They used two types of 10% vitamin C lotion, sodium ascorbate and ascorbic acid glucoside for six months in a splitfaced manner for dark circles. ...
... Vitamin C promotes collagen production and conceals color of blood stasis, which could improve appearance of dark circles under the lower eye lid. 34 Ohshima et al 34 showed that vitamin C and its derivatives, such as magnesium ascorbyl phosphate and ascorbic acid glucoside, inhibit melanogenesis in human melanocytes. They used two types of 10% vitamin C lotion, sodium ascorbate and ascorbic acid glucoside for six months in a splitfaced manner for dark circles. ...
Periorbital hyperpigmentation is a commonly encountered condition. There is very little scientific data available on the clinical profile and pathogenesis of periorbital hyperpigmentation. Periorbital hyperpigmentation is caused by various exogenous and endogenous factors. The causative factors include genetic or heredity, excessive pigmentation, postinflammatory hyperpigmentation secondary to atopic and allergic contact dermatitis, periorbital edema, excessive vascularity, shadowing due to skin laxity and tear trough associated with aging. There are a number of treatment options available for periorbital hyperpigmentation. Among the available alternatives to treat dark circles are topical depigmenting agents, such as hydroquinone, kojic acid, azelaic acid, and topical retinoic acid, and physical therapies, such as chemical peels, surgical corrections, and laser therapy, most of which are tried scientifically for melasma, another common condition of hyperpigmentation that occurs on the face. The aim of treatment should be to identify and treat the primary cause of hyperpigmentation as well as its contributing factors.
... Treatment of infraorbital dark circles and pu ness is challenging because of its multifactorial nature and lack of broadly applicable, effective treatments [21]. Individuals with dark circles and pu ness are perceived as tired, sad, stressed, and aged by societal and cultural communities, signi cantly impacting an individual's quality of life, and driving the demand and investment into measures to conceal and correct these concerns [5,31]. ...
Treatment of infraorbital dark circles and under-eye puffiness is challenging due to its multifactorial nature and lack of broadly applicable, effective treatments. A daily skincare treatment option that is multi-modal, effective, and tolerable across a broad patient population is an unmet need. A multi-corrective topical eye cream (MTEC) formulated with Tetrahexyldecyl (THD) ascorbate (vitamin C), prebiotic Inula Helenium, bioavailable peptides, botanical extracts, chrysin, and caffeine, is hypothesized to improve the appearance of infraorbital dark circles and under-eye puffiness by targeting micro-vasculature congestion and permeability, melanin accumulation and hemoglobin degradation related pigmentation, and skin health.
An IRB approved, open-label, 12-week clinical study set out to evaluate the efficacy and tolerability of the MTEC across a broad patient population including varying ethnicities and Fitzpatrick Skin Types (FST). Female subjects (n = 40) ages 35 to 60 years old, with moderate to severe under-eye dark circles, moderate under-eye puffiness, and mild-to-moderate fine lines were enrolled into the study. Objective (Chromameter, VISIA® imaging, and Laser Doppler) and subjective assessments (clinical grading and self-assessment questionnaire) were conducted at baseline and post-baseline timepoints.
The MTEC efficaciously demonstrated short-term and long-term improvements in objective and subjective assessments across a broad patient population. Specifically, the MTEC demonstrated significant improvement of infraorbital dark circles, mainly by the reduction of micro-vasculature congestion and permeability, melanin and hemoglobin degradation related pigmentation. Topical application of the MTEC may offer an effective and tolerable treatment option for infraorbital dark circles and puffiness.
... Vitamins C, E, and ferulic acid used in formulations help with hyperpigmentation. [58,59] Azelaic acid containing formulations help with hyperpigmentation. [60] ...
A cosmetic is “intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body for cleansing, beautifying, promoting attractiveness, or altering the appearance” while a drug is “intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease, i.e. it affects the structure and function of the body.” Cosmeceuticals attempt to interface between a pure cosmetic and a drug. ey are those which lie between a prescription and a non-prescription over-the-counter product. ey are medical products, which are cosmetics, with functional benefits for the skin, hair, and nails. Cosmeceuticals are disease-treating and disease-modifying. Dermatologists form a unique interface between products with perceived advantages and those with proven efficacy. In an attempt to hard-sell products with minimal side effects, certain compounds may contain sub-therapeutic doses of topical agents hence rendering them ineffective. On the other hand, certain products may form a useful bridge with a safety profile better than cosmetics in their class. is article reviews commonly available and evolving cosmeceuticals, their rationale, side effects, and use in dermatology practice with the aim to sensitize dermatologists about their perceived usefulness.
... Among topical drugs and methods, sunscreens and peels are widely used [16,17]. Tretinoin, vitamin C, arbutin, and azelaic acid are known to reduce melanin pigmentation [18][19][20][21][22]. ...
Periorbital hyperpigmentation (POH) is a frequent concern among both young and adult patients. The etiology is multifactorial with a genetic background. Prevalence is higher in darker skin types. It has been estimated as high as 30% in a recent Indian study. Females are often more disappointed by POH than males. Treatment has to consider underlying pathologies and patients’ needs. We present our treatment algorithm for POH. In this study, 74 patients with POH, 64 females (86.5%) and 10 males (13.3%), were treated. Of these, 39 patients (53%) had a family history of POH. The age range of patients was 18−57 years (average: 36.1 years). In case of tear trough deformity, soft tissue augmentation was used by injection of hyaluronic acid gel, calcium hydroxylapatite, or autologous fat. Blepharoplasty with partial fat pad resection or repositioning via arcus marginalis release was used to correct severe orbital fat herniation and excess of the lower lid skin. Melanin hyperpigmentation of the skin was improved by sessions of Q-switched 1064 and 532 nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser. Small vessels (capillaries and veins) were targeted by a 1064 nm long-pulsed Nd-YAG laser. Sessions of intense pulsed light (IPL) or CO2 fractional laser were employed to improve skin texture and fine lines. Topical hyaluronic acid-based formulations may be used as adjuvant self-treatment by patients. For pigmented and mixed-type POH, ultraviolet light protection is recommended as a maintenance treatment. By the use of various technologies, treatment can be individually tailored.
... Among topical drugs and methods, sunscreens and peels are widely used [16,17]. Tretinoin, vitamin C, arbutin, and azelaic acid are known to reduce melanin pigmentation [18][19][20][21][22]. ...
Periorbital hyperpigmentation (POH) is a frequent concern among both young and adult patients. The etiology is multifactorial with a genetic background. Prevalence is higher in darker skin types. It has been estimated as high as 30% in a recent Indian study. Females are often more disappointed by POH than males. Treatment has to consider underlying pathologies and patients’ needs. We present our treatment algorithm for POH. In this study, 74 patients with POH, 64 females
(86.5%) and 10 males (13.3%), were treated. Of these, 39 patients (53%) had a family history of POH.
The age range of patients was 1857 years (average: 36.1 years). In case of tear trough deformity, soft tissue augmentation was used by injection of hyaluronic acid gel, calcium hydroxylapatite, or autologous fat. Blepharoplasty with partial fat pad resection or repositioning via arcus marginalis release was used to correct severe orbital fat herniation and excess of the lower lid skin. Melanin hyperpigmentation of the skin was improved by sessions of Q-switched 1064 and 532 nm neodymiumdoped
yttrium aluminum garnet (Nd:YAG) laser. Small vessels (capillaries and veins) were targeted by a 1064 nm long-pulsed Nd-YAG laser. Sessions of intense pulsed light (IPL) or CO2 fractional laser were employed to improve skin texture and fine lines. Topical hyaluronic acid-based formulations may be used as adjuvant self-treatment by patients. For pigmented and mixed-type POH, ultraviolet light protection is recommended as a maintenance treatment. By the use of various technologies, treatment can be individually tailored.
... Ascorbic acid or vitamin C is a widely known watersoluble vitamin known for its anti-aging effect and antitanning effects (Ohshima et al. 2009;Zussman and Ahdout 2010). However, the molecule is unstable and can rapidly oxidize when exposed to heat and UV light (Austria et al. 1997). ...
Natural products have been used to protect the skin from harmful UV radiation for decades. Due to the ecotoxicological implications of synthetic sunscreen exposure in aquatic ecosystems, there is a greater need to explore alternative sources of UV filters. Recent research has focused on discovering novel UV absorbing photoprotective molecules from nature. In response to the excessive damage caused by UVB rays, plants induce the production of high concentrations of phytoprotective secondary metabolites and anti-oxidative enzymes. Despite promising UV absorbing and photoprotective properties, plant secondary metabolites have been underutilized in topical delivery due to low solubility and high instability. Numerous phytochemicals have been effectively nanosized, incorporated in formulations, and studied for their sustained effects in photoprotection. The present review outlines recent developments in nanosizing and delivering photoprotective crude plant extract and phytochemicals from a phytochemical perspective. We searched for articles using keywords: “UV damage,” “skin photoprotection,” “photodamage,” and “nano delivery” in varied combinations. We identified and reviewed literature from 43 original research articles exploring nanosized phytochemicals and crude plant extracts with photoprotective activity. Nanosized phytochemicals retained higher amounts of bioactive compounds in the skin and acted as depots for their sustained release. Novel approaches in nanosizing considerably improved the photostability, efficacy, and water resistance of plant secondary metabolites. We further discuss the need for broad-spectrum sunscreen products, potential challenges, and future growth in this area.
... In a split-face trial to evaluate efficacy of vitamin C in periorbital dark circles, it was found to increase dermal thickness due to collagen production and thereby reduced the appearance of dark circle. 13 ...
Background:
The periorbital region is among the first areas to be affected by the process of aging, which is influenced by genetic and constitutional factors. As the region plays an important role in overall facial appearance, rejuvenation of the area has immense cosmetic benefit and various treatment modalities have been used to achieve the same.
Aims:
This article reviews commonly used non-surgical and minimally invasive modalities for periorbital rejuvenation.
Methods:
The literature research considered published journal articles (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) and reference lists of respective articles. Only articles available in English were considered for this review.
Results:
Autologous platelet rich plasma (PRP) is increasingly used in dermatology for skin and hair conditions. The use of PRP is rapidly growing in popularity as a modality to achieve skin rejuvenation. The mechanism by which PRP leads to skin rejuvenation is by increasing the dermal fibroblast proliferation, expression of matrix metalloproteinase and collagen synthesis.
Conclusion:
The evidence discussed in this article indicates the increasing importance of minimally invasive modalities in periorbital rejuvenation and a promising role for PRP as solo therapy or in multimodality regimens.
... 78,79 Vitamin C in particular may serve to thicken eyelid dermal tissue, masking hemostasis-related discoloration. 80 Although hydroquinone has been the gold standard for hyperpigmentation, a recently released hydroquinone-free topical product targeting all major biochemical pathways of cutaneous pigmentation may lead to equivalent results without safety concerns associated with long-term use. 81,82 Topical application of growth factors may also help to reverse under-eye photodamage and laxity. ...
Dark under-eye circles are a common cosmetic complaint among patients, spanning all age groups and skin types. We review the anatomic and physiologic features of dark circles and highlight the varied treatment options available, including lasers to target pigment and superficial vasculature, fillers to reverse volume loss, and resurfacing to improve skin laxity and wrinkling.
Copyright © 2015 Elsevier Inc. All rights reserved.
... Heller et al. suggest that dark circles on the lower eyelid, which are caused by hyperpigmentation and poor blood circulation, are improved by ascorbic acid. In fact, in an in vivo study, ascorbic acid Na salt significantly improved dark circles due to effects on melanin, erythema, and dermal thickness [56]. These findings demonstrated the effects of ascorbic acid to suppress melanogenesis, to stabilize NOS, and to stimulate collagen synthesis. ...
Intracellular and extracellular oxidative stress initiated by reactive oxygen species (ROS) advance skin aging, which is characterized by wrinkles and atypical pigmentation. Because UV enhances ROS generation in cells, skin aging is usually discussed in relation to UV exposure. The use of antioxidants is an effective approach to prevent symptoms related to photo-induced aging of the skin. In this review, the mechanisms of ROS generation and ROS elimination in the body are summarized. The effects of ROS generated in the skin and the roles of ROS in altering the skin are also discussed. In addition, the effects of representative antioxidants on the skin are summarized with a focus on skin aging.
BACKGROUND
Periorbital dyschromia (POD) is a prevalent dermatologic problem with multifactorial etiology, making treatment outcomes inconsistent and unclear.
OBJECTIVE
To evaluate and compose a comprehensive review of topical ingredients proven to be effective in the treatment of POD.
MATERIALS AND METHODS
Scopus, PubMed, and OVID databases were searched in a span of 30 years through December 31, 2023, to identify articles with original findings of topical therapies for the treatment of POD. Findings of interest were objectively and subjectively measured regarding pigmentation, skin texture, aesthetic improvement, elasticity, hydration, and eye-bag volume.
RESULTS
The database searches yielded 339 unique studies. After screening and review, 22 studies were included totaling 13 nonrandomized control trials, 7 randomized clinical trials, 1 retrospective case series, and 1 prospective single-arm study. Studies included all reported statistically significant results with topical therapies inclusive of acids, bark extract, bicyclic monoterpene diols, caffeine, combo ingredient serums, ethyl ximenynate, gentiopicroside, glycosaminoglycans, growth factors, topical PRP, and vitamins.
CONCLUSION
The findings of this review suggest that topical therapies can be effective in the treatment of POD. Future trials should focus on delineating specific etiology of POD and evaluation of therapies specific to their cause.
Periorbital hyperpigmentation (POH), also referred to as periorbital melanosis or dark eye circles, is a common dermatological concern characterized by darkening of the skin around the eyes. This review article aims to comprehensively analyze the current understanding of POH, encompassing its epidemiology, etiopathogenesis, clinical manifestations, diagnosis and available treatment modalities, and focusing on patients’ skin color. The review also consolidates a grading system for POH and emphasizes the importance of accurate diagnosis using clinical examination, assessment scores, Wood’s lamp, ultrasonography, and dermoscopy. Treatment modalities range from non-pharmacological measures to topical agents, including kojic acid, alpha-arbutin, vitamin C, vitamin E, niacinamide, retinoids, and hydrating agents. The manuscript explores the efficacy of various skin-lightening agents, such as hydroquinone, and introduces emerging treatments like caffeine, carotenoids, lactic acid, curcumin, and vitamin K. Additionally, it delves into procedural treatments like chemical peels, lasers, blepharopigmentation, mesotherapy, platelet-rich plasma therapy, fillers, autologous fat transplantation, and surgical interventions. The comprehensive approach to understanding and managing POH presented in this review aims to provide clinicians with valuable insights into the diverse therapeutic options available for this challenging cosmetic concern.
Introduction
Dark under‐eye circles or periorbital hyperpigmentation constitute a prevalent and challenging cosmetic problem with diverse etiologies and types. While modifying exacerbating habits can provide partial relief for the pigmentary and vascular factors associated with this condition, and despite the abundance of available treatment options, there is currently a lack of gold‐standard evidence‐based treatments proposed for curing this disorder.
Objectives
This study aimed to assess the safety and effectiveness of carboxytherapy in treating periorbital hyperpigmentation.
Material and Methods
In this 4‐week single‐arm clinical trial, 20 eligible Iranian patients with symmetric periorbital hyperpigmentation received weekly intradermal carboxytherapy. The treatment involved administering 10–20 mL of CO2 at a rate of 20 mL/min and a temperature of 15°C for a duration ranging from a few seconds to 1 min. Follow‐up assessments were conducted 1 month after the final session. The primary outcome was defined as the changes in ΔE or the variations in pigmentation observed between the orbital and extra‐orbital skin before and after the trial.
Results
The patients reported satisfaction with the statistically significant reduction in hyperpigmentation achieved through carboxytherapy in the lateral (p = 0.002), middle (p = 0.001), and medial (p = 0.001) regions of the periorbital area. The total response rate of the patients was estimated at 20%. Patient satisfaction exceeded ΔE changes, with no significant linear relationship (p = 0.084).
Conclusion
Carboxytherapy can be proposed as an effective and safe treatment for periorbital hyperpigmentation.
Background
Treatment of infraorbital dark circles and under‐eye puffiness is challenging due to its multifactorial nature and lack of broadly applicable, effective treatments. A daily skincare treatment option that is multimodal, effective, and tolerable across a broad patient population is an unmet need.
Aim
A multicorrective topical eye cream (MTEC) formulated with Tetrahexyldecyl (THD) ascorbate (vitamin C), prebiotic Inula Helenium , bioavailable peptides, botanical extracts, chrysin, and caffeine is hypothesized to improve the appearance of infraorbital dark circles and under‐eye puffiness by targeting microvasculature congestion and permeability, melanin accumulation and hemoglobin degradation‐related pigmentation, and skin health.
Methods
An IRB approved, open‐label, 12‐week clinical study set out to evaluate the efficacy and tolerability of the MTEC across a broad patient population including varying ethnicities and Fitzpatrick Skin Types (FST). Female subjects ( n = 40) ages 35–60 years old, with moderate‐to‐severe under‐eye dark circles, moderate under‐eye puffiness, and mild‐to‐moderate fine lines were enrolled into the study. Objective (Chromameter, VISIA® imaging, and Laser Doppler) and subjective assessments (clinical grading and self‐assessment questionnaire) were conducted at baseline and post‐baseline timepoints.
Results
Thirty‐seven subjects completed the study, and the MTEC efficaciously demonstrated short‐term and long‐term improvements in objective and subjective assessments across a broad patient population. Specifically, the MTEC demonstrated significant improvement of infraorbital dark circles, mainly by the reduction in microvasculature congestion and permeability, melanin, and hemoglobin degradation‐related pigmentation.
Conclusion
Topical application of the MTEC may offer an effective and tolerable treatment option for infraorbital dark circles and puffiness.
Periorbital hyperpigmentation (POH) is a common aesthetic concern that impacts patients' emotional well-being and quality of life. POH can be difficult to manage as the etiology is often multifactorial or difficult to elucidate. An understanding of different contributing factors and ability to classify hyperpigmentation can aid in the management of POH. Classification of POH is divided into pigmented, vascular, structural, and mixed subtypes. A wide array of treatment options has been proposed belying the challenges inherent to improving POH. Modalities vary from topical therapies, chemical peels, dermal fillers, and lasers, to surgical intervention. Because POH can be multifactorial, successful management of POH will depend on elucidating the etiology and often requires a combination of therapies.
In this report the use of eye cosmetic products and procedures and how this represents a lifestyle challenge that may exacerbate or promote the development of ocular surface and adnexal disease is discussed. Multiple aspects of eye cosmetics are addressed, including their history and market value, psychological and social impacts, possible problems associated with cosmetic ingredients, products, and procedures, and regulations for eye cosmetic use. In addition, a systematic review that critically appraises randomized controlled trial evidence concerning the ocular effects of eyelash growth products is included. The findings of this systematic review highlight the evidence gaps and indicate future directions for research to focus on ocular surface outcomes associated with eyelash growth products.
The skin aging process is caused by an interaction of epigenetic, genetic, and environmental factors. Thus, skin suffers from extrinsic and intrinsic factors enhancing this process. Both factors contribute to ROS formation in skin aging. ROS is necessary for intrinsic aging; it is produced mainly in mitochondria due to aerobic metabolic reactions. As for extrinsic aging, smoking, UV, and hyperglycemia lead to ROS generation. In skin aging process, generated excessive ROS activates MAPKs and thus induces NF-κB transcription factors. This activation inhibits TGF-β signaling pathway and increases MMPs expression, leading to decreased collagen synthesis and breakdown. Excess ROS related to aging-associated diseases also accelerates skin aging.On the other hand, metformin, an antidiabetic agent, via inactivating NF-kB, inhibits oxidative stress, ameliorates inflammatory reactions, improves mitochondrial function, and regulates cell death. Up-to-date evidence suggests that NF-kB signaling dysfunction and dysregulation are related to skin aging. There are current mechanisms and novel strategies for the therapeutic manipulation of NF-kB in treating skin aging. This chapter summarizes the current role of NF-kB in dermal aging, underlines the molecular mechanism of metformin in skin aging, attributes its effects to the modulation of NF-kB, and presents novel therapeutic approaches to skin aging through this modulation.
Keywords: NF-κB signaling pathway. Metformin. Skin aging. Collagen. MMP
BACKGROUND: The main function of vitamin C for skin health is as an antioxidant, combating environmental oxidative stress, which helps the natural regeneration of environmental oxidative stressors, collagen formation and brightening the skin. Humans cannot synthesize their own vitamin C, so to meet the vitamin C needs of the body, humans must consume vitamin C from fresh fruits and vegetables. In addition to oral and topical use, the practice of using vitamin C by injection has also been widely spread in major cities in Indonesia. Taking vitamin C is not something bad, but using vitamin C that is not according to the recommended dosage can have unwanted effects on health. OBJECTIVE: This study aims to determine the level of knowledge of students at the Faculty of Medicine, Universitas Sumatera Utara to regarding the role of vitamin C for skin health in 2020. METHODS: This study used a descriptive observational method with a cross sectional design. The sample size in this study was 247 people. The samples used were students of Faculty of Medicine at the Universitas Sumatera Utara class 2017, 2018, and 2019. Data on student knowledge levels collected from the results of filling out the questionnaire will be grouped using the Guttman scale and forwarded for further data processing using the Statistical Package for Social Sciences (SPSS) program 25 . RESULTS : In this study it was found that 86.3% of respondents had sufficient knowledge about the role of vitamin C for skin health, 91.2% of female respondents had sufficient knowledge, 81.5% of male respondents had sufficient knowledge. Based on how to use vitamin C, it can be seen that 41.9% of students have high knowledge about the use of vitamin C orally, 60% of respondents have sufficient knowledge about the use of vitamin C topically, and 50.4% of respondents have sufficient knowledge about its use vitamin C by injection. CONCLUSION: The level of knowledge of students at the Faculty of Medicine at the Universitas Sumatera Utara, for 2017, 2018 and 2019 regarding the role of vitamin C for skin health is sufficient. There are differences in the level of knowledge according to gender in this study, it was found that women have a better level of knowledge than men.
Periorbital hyperpigmentation (POH) is a common aesthetic concern that impacts patients' emotional well-being and quality of life. POH can be difficult to manage as the etiology is often multifactorial or difficult to elucidate. An understanding of different contributing factors and ability to classify hyperpigmentation can aid in the management of POH. Classification of POH is divided into pigmented, vascular, structural, and mixed subtypes. A wide array of treatment options has been proposed belying the challenges inherent to improving POH. Modalities vary from topical therapies, chemical peels, dermal fillers, and lasers, to surgical intervention. Because POH can be multifactorial, successful management of POH will depend on elucidating the etiology and often requires a combination of therapies.
Nanotechnology is an innovative area of science that deals with things smaller than 100 nanometers. The influence of nanotechnology in the cosmetic industry is overwhelming since it can enhance the properties attained by the particles at the nano level which includes color, solubility, etc, and also promotes the bioavailability of API. A plethora of nanomaterials can be employed in cosmetics including organic and inorganic nanoparticles. Unlike orthodox carriers, they facilitate easy penetration of the product into the skin and thereby increasing the stability and allowing a controlled drug release so that they can permeate deeper into the skin and start revitalizing it. Nanomaterials rejuvenate the skin by forming an occlusive barrier to inhibit the loss of water from the skin’s surface and thereby moisturize the skin. Nano-cosmeceuticals are used to provide better protection against UV radiation, facilitate deeper skin penetration, and give long-lasting effects. Although they still have some safety concerns, hence detailed characterization or risk assessments are required to fulfill the standard safety requirements. In this review, an attempt is made to make a brief overview of various nanocosmeceutical skincare and anti-aging products.
Introduction:
Ascorbic acid (AA) is a powerful antioxidant capable of acting significantly both in the prevention and treatment of the skin aging process. One way to assess the in vivo efficacy of anti-aging treatments is by using the high-frequency ultrasound (HFUS) skin image analysis technique, a non-invasive approach that allows for a new level of evaluating the effectiveness of dermatological and cosmetic products. The aim of the present study was to assess the performance of a topical emulsion of liquid crystalline structures containing AA using the 50 MHz HFUS skin image analysis method.
Methods:
Twenty-five healthy female participants between 35 and 60 years were included, all of whom randomly applied a placebo formulation and an AA-containing formulation to each forearm, once a day, for 30 days. HFUS measurements were performed before using the products (T0), 2 h later (T2h), and after 30 days of use (T30d). The analyzed parameters included total skin, dermal, and epidermal echogenicity; variation and mean thickness of total skin, the epidermis and dermis; and surface roughness. Statistical analyses were performed using the Friedman test, followed by Dunn's test for comparisons of multiple means (α = 0.05).
Results:
A significant increase in total skin and dermal echogenicity was observed after topical AA application.
Conclusion:
Our findings suggest that collagen synthesis significantly increased after topical therapy with AA, which was responsible for the increment in dermal echogenicity. This study showed, through the HFUS technique, that the topical use of AA promoted dermal redensification after 30 days of application.
In this research, we propose a method using a spectroscopic camera to estimate the concentration of blood in different layers of skin tissue. For the demonstration that shows the possibility of application of our method, we conducted a stimulation experiment on 20 subjects involving hot or carbonated baths to promote blood circulation, and estimated the blood concentration before and after stimulation. The results indicate the possibility of estimating blood concentration by proposed method based on spectroscopic images.
Infraorbital dark circles are a significant esthetic concern with few publications however offering evidence-based recommendations for their classification and consequent management. A literature review has been undertaken to classify dark circles based on etiology: shadowing, vascular, idiopathic hyperpigmentation, post-inflammatory hyperpigmentation, constitutional and offer an analysis of current treatment modalities and their effectiveness in managing specific types of infraorbital circles. This review aims to provide a detailed account of dark circle etiology, assessment and management.
Background:
Periorbital hyperpigmentation (POH) is an aesthetic concern for patients. Etiologies of the condition include pigmentary, structural, vascular, and mixed causes.
Objective:
To systematically review the current literature for treatment of POH.
Methods:
A systematic literature review was performed on PubMed. Search terms included "infraorbital dark circles," "dark circles," "periorbital hyperpigmentation," "idiopathic hyperchromia AND orbital," "under-eye circles," "ICHOR (idiopathic cutaneous hyperchromia of the orbital region)," "dark circles" AND "treatment," and "filler" AND "dark circles."
Results:
A total of 39 studies were included. Effective treatments for POH include lasers, topical creams and serums, fillers, chemical peels, carboxytherapy, plasma-rich platelet injections, blepharoplasty, and normobaric oxygen.
Conclusion:
Soft tissue fillers and autologous fat grafting are most effective in treating dark circles due to volume loss. Blepharoplasty surgery is best when excessive skin laxity is the underlying cause. Various topical creams and chemical peels are useful in treating pigment-based POH, whereas lasers are mildly to moderately beneficial for both vascular and pigment types. Given the scarcity of high-quality evidence supporting these results, recommendations should be interpreted selectively. Additional randomized clinical trials studying POH will be helpful.
Dermatological disorders can be reflected in the eye and the periorbital area. Various skin diseases can affect the skin of the periorbital area e.g. dermatitis, vitiligo, xanthelasma, hidrocystomas, syringomas, milia, etc. Other cutaneous disorders may have associated ocular involvement e.g. rosacea, port-wine stain and nevus of Ota. Some infectious diseases can affect both the skin and eyes e.g. herpes simplex and herpes zoster. Systemic diseases can have ocular, as well as, dermatological involvement e.g. amyloidosis, dermatomyositis, sarcoidosis and Bechet’s disease. Periorbital dermatological procedures e.g. periorbital chemical peeling and laser procedures, and their expected complications, can be of interest to ophthalmologists.
Background:
Tear trough and infraorbital region changes are one of the first signs recognizable aging. This is a common consultation for cosmetic dermatologists and there are many treatment options available.
Objective:
This article provides a review of the anatomy and changes that occur in the infraorbital region as we age. We also suggest the use of the osseous, color, underlying anatomy, laxity, adipose, rhytides (OCULAR) mnemonic to evaluate these changes and review the literature for treatments options.
Materials and methods:
A literature search was performed through PubMed, using search terms "Tear trough," "Infra-orbital," "Dark-circles," "Lower-Eyelid," and "Midface."
Results:
Fillers, lasers, radiofrequency devices, chemical peels, various topicals, and botulinum toxin are available non-surgical treatment options discussed in the literature found to significantly improve and rejuvenate the infraorbital region.
Conclusion:
A complete understanding of the anatomy and changes that occur with aging are of most importance when assessing the infraorbital region. Organizing these changes into the OCULAR mnemonic is one way to assess the infraorbital region and achieve optimal rejuvenation.
There are a number of different patterns of pigment variation that lie within the spectrum of normal pigmentation. In general, these are typically more common and more prominent in skin of color. The most common of these will be discussed in this chapter including pigmentary demarcation lines, periorbital hyperpigmentation, acquired idiopathic pattern facial pigmentation (AIPFP), oral mucosal hyperpigmentation, palmar/plantar melanotic macules, and longitudinal physiologic melanonychia.
Introduction:
Periorbital Melanosis (POM) is a very common esthetic condition, yet there is no definite treatment modality. Topical therapy is the mainstay of treatment which includes chemical peels, vitamin C, and other depigmenting agents.
Objective:
To compare clinical efficacy, safety, and tolerability of 20% glycolic acid peels, 15% lactic acid peels, and topical 20% vitamin C in treatment of constitutional type of POM in Indian patients.
Method:
Ninety patients of constitutional POM were enrolled for 12 weeks. The patients were distributed into three groups. One-third of patients underwent 3-weekly GA peel, another one-third underwent 3-weekly lactic peel, and rest applied vitamin C daily. Clinical improvement was assessed objectively using POM grading. Patient's and physicians global assessment along with patient's global tolerance was also evaluated.
Results:
More than 50% improvement in POM was observed in 73.34% of patients on GA peel, 56.67% on lactic peel, and 26.67% on vitamin C. On comparing improvement with respect to duration of therapy, GA peel was significantly more effective than lactic peel from 12 weeks onward, while it was more effective than vitamin C from 6 weeks onward. Lactic peel was more effective than vitamin C from 6 weeks onward. Physician and patient global assessment was excellent with glycolic peel followed by lactic peel and vitamin C. The incidence of adverse effect was maximum with GA peel followed by lactic peel and vitamin C.
Conclusion:
Glycolic peel was best among the three modalities, although it was associated with increased rate of side effects.
Intracellular and extracellular oxidative stress initiated by reactive oxygen species (ROS) advances skin aging, which is characterized by wrinkles and atypical pigmentation. Because UV enhances ROS generation in skin cells, skin aging is generally discussed in relation to UV exposure. The use of antioxidants is one of the effective approaches to prevent symptoms related to photo-induced aging of the skin. In this chapter, alterations of the skin caused by chronic solar exposure are discussed in relation to the influence of ROS/oxidative stress. After summarizing the mechanisms of the generation and elimination of ROS in the body, the roles of ROS in altering the skin are discussed. Finally, the effects of representative antioxidants on the skin are introduced with a focus on skin aging.
Objective:
Examine clinical trials performed for depigmenting agents in order to determine the most effective and well-tolerated depigmenting agent.
Methods:
We searched clinical trials, published and unpublished, performed for hydroquinone, ascorbic acid, azelaic acid, retinol and niacinamide in the period 2009 till present. Studies were examined based on participant information, design, duration, intervention, outcome measurements and statistical significance.
Results:
Sixty-one studies were examined, 40 published and 21 unpublished. Design, outcome measures and intervention showed sources of bias were not avoided. Only 30% of published trials were double-blind, 27% used a placebo and 80% used subjective measurements for their results. Unpublished trials follow similar outcomes, however, did not provide any significant results.
Conclusion:
Based on these results, we are unable to recommend a safer, more effective depigmenting agent. Lack of thorough trials limits us from accepting depigmenting agent full evaluation. To accept a depigmenting agent, its duration must test for long-term safety, clinical trial must be double-blind and comparative, use participants of the correct skin type and measure outcomes objectively. In addition, lack of results for parallel unpublished studies leaves room for discussion. Efforts toward creating more effective formulations are welcomed.
Cutaneous hyperpigmentations are frequent complaints, motivating around 8.5% of all dermatological consultations in our country. They can be congenital, with different patterns of inheritance, or acquired in consequence of skin problems, systemic diseases or secondary to environmental factors. The vast majority of them are linked to alterations on the pigment melanin, induced by different mechanisms. This review will focus on the major acquired hyperpigmentations associated with increased melanin, reviewing their mechanisms of action and possible preventive measures. Particularly prominent aspects of diagnosis and therapy will be emphasized, with focus on melasma, post-inflammatory hyperpigmentation, periorbital pigmentation, dermatosis papulosa nigra, phytophotodermatoses, flagellate dermatosis, erythema dyschromicum perstans, cervical poikiloderma (Poikiloderma of Civatte), acanthosis nigricans, cutaneous amyloidosis and reticulated confluent dermatitis.
It is often difficult to differentiate between allergic and irritant patch test reactions by visual inspection. The purpose of this study was to test an image analysis-based method that differentiates between the two reactions by quantifying the degree of erythema at the patch test site.
A total of 172 Japanese patients were patch-tested with sodium lauryl sulfate (SLS) and nickel sulfate, followed by digital photography and visual evaluation of the patch test areas by dermatologists at 48 and 72 h. The digital images were converted to erythema index (EI) images by image processing, and changes in ΔEI (the difference in the EI between the patch test site and the adjacent normal skin) values were analyzed.
The ΔEI was significantly increased at 72 h relative to that at 48 h for positive nickel sulfate reactions (P < 0.0001), while no significant difference in the ΔEI was found for SLS reactions.
Using image analysis, allergic patch test reactions may be distinguished from irritant reactions by evaluating the change in the degree of erythema at 48 and 72 h.
The concept of a nanocarrier with a self-antioxidative property to deliver and stabilize a labile drug while at the same time providing a free radical scavenging activity is demonstrated. Curcumin was grafted onto a poly(vinyl alcohol) [PV(OH)] chain, and the nanocarriers fabricated from the obtained curcumin-grafted PV(OH) polymer [CUR-PV(OH)] showed a good free radical scavenging activity. Ascorbyl palmitate (AP) could be effectively loaded into the CUR-PV(OH) at 29% by weight. The CUR-PV(OH)-encapsulated AP was 77% more stable than the free (unencapsulated) AP, and 47% more stable than AP encapsulated in the control nanocarrier with no antioxidative property [cinnamoyl-grafted PV(OH); CIN-PV(OH)]. Although coencapsulation of curcumin and AP into CIN-PV(OH) showed some improvement on the AP stability, AP was more stable when encapsulated in CUR-PV(OH). Compared with the free AP, encapsulated AP within the CUR-PV(OH) nanocarriers showed not only a better penetration into pig skin dermis via hair follicle pathway followed by the release and diffusion of the AP, but also a greater AP stability after skin application. Although a proof of principle is shown for CUR-PV(OH) and AP, it is likely that other carriers of the same principal could be designed and applied to different oxidation-sensitive drugs. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
Background:
Periocular "dark circles" fall among the most difficult chief complaints to address. In most cases, we have little information regarding etiology and no gold-standard treatment option. The extent of the problem is reflected in the sheer number of products on the market advertised to either lighten or cover the pigmentation.
Objective/methods:
To present dermatologists with a complete review of the literature with regard to anatomy, definition, etiology, and treatment of periocular hyperpigmentation.
Conclusions:
Our understanding of the causes and treatment of periocular hyperpigmentation continues to advance. Nevertheless, we are in need of additional controlled clinical trials and novel therapeutic options. Individual patients will likely benefit most from a combination of approaches. Although more randomized clinical studies are necessary, Pfaffia paniculata/Ptychopetalum olacoides B.⁄Lilium candidum L.-associated compound cream seems to be a promising option, with 90% improvement. For patients with increased melanin deposition, quality-switched ruby laser therapy could offer a better treatment option. In the hands of experienced professionals, a surgical option might be suitable, either by autologous fat transplantation or hyaluronic acid filler.
Background
Dark circles under or around the eyes is a cosmetic problem for a large number of people. It is a condition of unknown etiology characterized by the darkening of the eyelids and periorbital skin. The aim of this study was to determine histopathological changes associated with cutaneous idiopathic hyperchromia of the orbital region (CIHOR).
Methods
Twenty-eight adult patients with CIHOR were consecutively selected for the study. Biopsy specimens were taken from the darkened skin of the eyelid and from the normal retroauricular skin as a control.
Results
Hemosiderin was absent in all cases. The increase in melanin content in the papillary dermis was slight in mild clinical cases and moderate in both the moderate and severe clinical cases of CIHOR. Mild dilation of blood vessels was observed in the papillary dermis at the different clinical levels of CIHOR severity, while in the reticular dermis, blood vessels showed moderate dilation and few melanophages were found.
Conclusion
An increase in melanin content was the most marked histological change in specimens of darkened skin. Dilation of dermal blood vessels may contribute to the severity of CIHOR. Hemosiderin was not observed in any case.
Level of Evidence III
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www. springer. com/ 00266.
BACKGROUND Periorbital hyperpigmentation (POH) presents with a dark area surrounding the eyelids. It is an ill-defined condition, and the pathogenesis can be multifactorial.OBJECTIVE This epidemiologic study was conducted to assess the prevalence of periorbital hyperpigmentation in Singapore in an attempt to propose a classification.MATERIALS AND METHODS One thousand consecutive patients attending the general dermatology clinic at the National Skin Center were enrolled in the study to assess for POH, of whom 200 with POH were examined and investigated to define the cause of POH. The possible causes were determined according to a detailed history, clinical examination, and assessment by three dermatologists. The extent of the POH was measured using a mexameter.RESULTS The commonest form of POH was the vascular type (41.8%), followed by constitutional (38.6%), postinflammatory hyperpigmentation (12%), and shadow effects (11.4%). The vascular type was seen predominantly in Chinese, whereas as the constitutional type was most common in Indians and Malays.CONCLUSION The vascular form of POH was the predominant type. We propose a comprehensive classification for POH that we hope will influence the choice of treatment modalities used in managing POH in the future.Unilever R&D Trumbul, USA provided funding for this study.
New double-chain zwitterionic surfactants were shown to undergo spontaneous dispersion as vesicles in water by means of simple
dilution of the lamellar phase. The molecular parameters of relevance were investigated in a systematic study of the structure
of the lamellar phase and of the ability of spontaneous formation of vesicles in a series of homologous zwitterionic surfactants.
Thus, the double-chain zwitterionic surfactants which occupies a small interfacial area per molecule in spite of the large
size of their hydrophilic headgroup can form spontaneous vesicles. In this case, the bending modulus ¯k of the surfactant film is strongly negative and the short-range repulsive interactions between hydrophilic groups protruding
from the surfactant films into water allow a large swelling of the lamellar phase, and are the origin of the colloidal stability
of the vesicles dispersion.
Periorbital hyperpigmentation (POH) presents with a dark area surrounding the eyelids. It is an ill-defined condition, and the pathogenesis can be multifactorial.
This epidemiologic study was conducted to assess the prevalence of periorbital hyperpigmentation in Singapore in an attempt to propose a classification.
One thousand consecutive patients attending the general dermatology clinic at the National Skin Center were enrolled in the study to assess for POH, of whom 200 with POH were examined and investigated to define the cause of POH. The possible causes were determined according to a detailed history, clinical examination, and assessment by three dermatologists. The extent of the POH was measured using a mexameter.
The commonest form of POH was the vascular type (41.8%), followed by constitutional (38.6%), postinflammatory hyperpigmentation (12%), and shadow effects (11.4%). The vascular type was seen predominantly in Chinese, whereas as the constitutional type was most common in Indians and Malays.
The vascular form of POH was the predominant type. We propose a comprehensive classification for POH that we hope will influence the choice of treatment modalities used in managing POH in the future.
The interpretation of patch test reactions may vary between examiners. As test results are graded, an issue also arises when differing degrees of erythema are placed in the same grade. The purpose of this study was to quantitatively evaluate the degree of erythema in patch tests using image analysis and to study the usefulness of this method by comparing it with visual grading.
A total of 121 Japanese patients were patch tested with various materials. At 48 h, digital photographs of the patch test areas were taken, in addition to a visual evaluation by dermatologists. Digital images of the areas were converted to erythema index (EI) images using image processing and both EI and ΔEI (the difference between the patch test site and adjacent normal skin) values of the patch test sites were compared with the corresponding visual grades.
An excellent linear correlation (r=0.95) was found between ΔEI and visual grades, although EI also significantly correlated with visual grades. There were significant differences (P<0.0001-0.05) between the mean ΔEI values of any two adjacent visual grades.
ΔEI values derived from image processing appear to be suitable for the quantitative evaluation of erythema in patch tests. This method may be helpful in overcoming the subjectiveness of visual evaluation and for training non-experts in patch testing.
After prolonged exposure to ascorbate, collagen synthesis in cultured human skin fibroblasts increased approximately 8-fold with no significant change in synthesis of noncollagen protein. This effect of ascorbate appears to be unrelated to its cofactor function in collagen hydroxylation. The collagenous protein secreted in the absence of added ascorbate was normal in hydroxylysine but was mildly deficient in hydroxyproline. In parallel experiments, lysine hydroxylase (peptidyllysine, 2-oxoglutarate:oxygen 5-oxidoreductase, EC 1.14.11.4) activity increased 3-fold in response to ascorbate administration whereas proline hydroxylase (prolyl-glycyl-peptide, 2-oxoglutarate:oxygen oxidoreductase, EC 1.14.11.2) activity decreased considerably. These results suggest that collage polypeptide synthesis, posttranslational hydroxylations, and activities of the two hydroxylases are independently regulated by ascorbate.
Blood flow stagnation is said to be an important factor for the incidence of dark eye circles, but there are few reports, which have studied dark eye circles and the relationship to blood flow. We have examined dark eye circles dermatologically using a non-invasive method and made clear the factor related to it. We have also studied the effect of newly developed cosmetics on improvement of dark eye circles. Melanin and haemoglobin content, haemoglobin oxygen saturation and blood flow rate were measured to compare dark eye circles with a normal control. An increased amount of haemoglobin and decreased haemoglobin oxygen saturation were observed at the site of dark eye circles. We also observed that the blood flow rate was slow at dark eye circles in comparison with cheek. From these results, blood flow stagnation seems to be one of the factors that could induce dark eye circles. In addition, the increase of melanin at dark eye circles was also observed in older subjects. It was considered that not only congestion but also an increase of melanin content in the skin could induce dark eye circles. On the basis of these results, we developed anti-dark eye circle cosmetics that can improve blood circulation, reduce melanin content and maintain high moisture retention in the skin. After 3 weeks’ usage of this product, it was confirmed that dark eye circles were improved, judging from the result of non-invasive instrumental measurements.
Ultraviolet radiation damage to the skin is due, in part, to the generation of reactive oxygen species. Vitamin C (L-ascorbic acid) functions as a biological co-factor and antioxidant due to its reducing properties. Topical application of vitamin C has been shown to elevate significantly cutaneous levels of this vitamin in pigs, and this correlates with protection of the skin from UVB damage as measured by erythema and sunburn cell formation. This protection is biological and due to the reducing properties of the molecule. Further, we provide evidence that the vitamin C levels of the skin can be severely depleted after UV irradiation, which would lower this organ's innate protective mechanism as well as leaving it at risk of impaired healing after photoinduced damage. In addition, vitamin C protects porcine skin from UVA-mediated phototoxic reactions (PUVA) and therefore shows promise as a broad-spectrum photoprotectant.
This study was designed to investigate the biochemical mechanisms responsible for the connective tissue changes seen in actinically damaged skin, which is characterized histologically by diminution and ultrastructural alterations of collagen fibrils and deposition of elastotic material in the papillary dermis. We hypothesized that ultraviolet light could stimulate synthesis of interstitial collagenase in the skin, resulting in collagen degradation. Monolayer cultures of human fibroblasts or keratinocytes were irradiated with ultraviolet A (UVA) or ultraviolet B (UVB) radiation and interstitial collagenase or its inhibitor, TIMP (tissue inhibitor of metalloproteinases) assessed in the conditioned medium with Western immunoblots 24 h after irradiation. Northern blot analysis of the irradiated fibroblasts with a cDNA probe representing collagenase was also performed. Cell viability was greater than 90% with all doses of UV radiation studied. A dose-related increase in immunoreactive collagenase was detected in the medium of fibroblasts irradiated with 0-10 J/cm2 of UVA radiation as well as a parallel increase in the collagenase mRNA in the irradiated cells. UVA radiation stimulated collagenase synthesis in both neonatal and adult fibroblasts. TIMP production in UVA-irradiated fibroblasts increased to a lesser degree than did collagenase and its increase did not parallel the increase in collagenase. UVB (0-100 mJ/cm2) did not stimulate collagenase production by fibroblasts. In contrast to the stimulation of collagenase production by fibroblasts, a slight decrease in immunoreactive collagenase was seen in UVA-irradiated keratinocytes. These data suggest that direct stimulation of collagenase synthesis by human skin fibroblasts by UVA radiation may contribute to the connective tissue damage induced by ultraviolet radiation leading to photoaging.
In confluent human skin fibroblasts maintained in 0.5% serum-supplemented medium. L-ascorbate specifically stimulated the rate of incorporation of labeled proline into total collagenase-sensitive protein, without changing the specific activity of the intracellular free proline. This influence of ascorbate reached a maximum at 30 microM and continued for at least 4 days, resulting in a 4-fold increase. The ascorbate effect occurred in cells at both confluent and subconfluent densities and was evident at all serum concentrations from 0.5-20%. The effect was independent of duration of the radioactive pulse between 2-6 h. D-Ascorbate, D-isoascorbate, and L-dehydroascorbate also stimulated collagen synthesis but at considerably higher concentrations, i.e., 250-300 microM. The stimulation of collagen synthesis by ascorbate and its analogs was accompanied by a decline in prolyl hydroxylase activity and a rise in lysyl hydroxylase activity; again L-ascorbate was found to be most effective. Dimethyltetrahydropterine and L-lactate failed to produce these effects.
Like other cytokines, IL-6 has been reported to stimulate collagenase. In this study we were interested in whether IL-6 is involved in the ultraviolet (UV) mediated up-regulation of fibroblast-derived collagenase. Confluent fibroblast monolayers were irradiated under standardized conditions. Following UVA irradiation the bioactivity of IL-6 increased up to fiftyfold in the supernatants of irradiated compared to mock-irradiated fibroblasts. As determined by Northern blot analysis this was also reflected on the pre-translational level by a tenfold increase of IL-6-specific mRNA following UVA irradiation. Induction of IL-6-specific mRNA was maximal at 6 h post-irradiation, thus clearly preceding the maximal induction of collagenase mRNA at 24 h post-irradiation. To elucidate the regulatory role of IL-6 in the UVA induction of fibroblast-derived collagenase, monospecific polyclonal neutralizing antibodies directed against recombinant human IL-6 and antisense oligonucleotides specifically inhibiting the translation of IL-6 mRNA were used at various concentrations. The amount of UVA-induced collagenase mRNA was reduced in a dose-dependent manner when antibodies or specific antisense oligonucleotides were present during and after irradiation. Taken together our data provide first evidence that UVA enhances IL-6 synthesis and secretion in fibroblasts. IL-6 induces via an autocrine mechanism collagenase and may thus contribute to the actinic damage of the dermis.
We report a method for quantitative analysis of erythema and pigmentation using a videomicroscope interfaced with a computer. The analysis was carried out by examining the brightness intensity of every picture element, composed of an image picked up from each band of red, green, and blue, and by deriving the quasi-absorbance value (absorbance index) from the mean brightness for each band. In assessments of UV-induced erythema and tanning, excellent linear correlations were found between the results obtained with our system and those with a narrow-band reflectance spectrometer. Moreover, the absorbance indices of haemoglobin and melanin solutions showed linear relationships with their concentrations in in vitro examination. As the monitored picture becomes out of focus if incorrect pressure is exerted on the skin, and as regions of interest can be chosen from a magnified image, this system offers excellent interobserver reproducibility, and is suitable for the evaluation of erythema or pigmented lesions which are too small or irregular to quantify by conventional methods such as colorimetry.
Decreased collagen synthesis and loss of responsiveness to growth factors are well known phenomena in in vivo or in vitro aged cells. Ascorbic acid and some cytokines such as transforming growth factor-beta and interferon-gamma are important regulators of collagen synthesis. To investigate the responsiveness of fibroblasts with regard to the photoaging and aging process, we examined the effect of ascorbic acid, TGF-beta, and IFN-gamma on collagen synthesis in dermal fibroblasts from three newborn foreskins (1 day old) and in both exposed and unexposed skin fibroblasts from 4 old individuals (60-76 years old) cultured in monolayer and in collagen gel. We demonstrated that basal levels of collagen synthesis decreased with increasing age. Photoaged fibroblasts in collagen gel showed greater basal collagen synthesis than aged fibroblasts in the same individuals, but similar basal collagen synthesis in monolayer cultures. Even though basal levels of collagen synthesis in collagen gel are downregulated in a photoaging- and aging-dependent manner, collagen synthesis by ascorbic acid in collagen gel, and by TGF-beta and IFN-gamma in both monolayer culture and collagen gel were regulated in a photoaging- and aging-independent manner. In monolayer culture, however, the responsiveness to ascorbic acid in newborn fibroblasts was greater than in photoaged and aged fibroblasts. Our results suggest that there are differences in collagen synthesis between photoaged and aged cells, depending on culture conditions. Responsiveness to ascorbic acid, TGF-beta and IFN-gamma related to collagen synthesis in photoaged and aged fibroblasts in collagen gel appears to be the same as in newborn fibroblasts, even though basal levels of collagen synthesis are downregulated in a photoaging- or aging-dependent manner.
Aging of the population, in particular the "baby boomers," has resulted in increased interest in methods of reversal of photodamage. Non-invasive treatments are in high demand, and our knowledge of mechanisms of photodamage to skin, protection of the skin, and repair of photodamage are becoming more sophisticated and complex.
The objective of this study is to determine if the topical use of a vitamin C preparation can stimulate the skin to repair photodamage and result in clinically visible differences, as well as microscopically visible improvement.
Ten patients applied in a double-blind manner a newly formulated vitamin C complex having 10% ascorbic acid (water soluble) and 7% tetrahexyldecyl ascorbate (lipid soluble) in an anhydrous polysilicone gel base to one-half of the face and the inactive polysilicone gel base to the opposite side. Clincial evaluation of wrinkling, pigmentation, inflammation, and hydration was performed prior to the study and at weeks 4, 8, and 12. Two mm punch biopsies of the lateral cheeks were performed at 12 weeks in four patients and stained with hematoxylin and eosin, as well as in situ hybridization studies using an anti-sense probe for mRNA for type I collagen. A questionnaire was also completed by each patient.
A statistically significant improvement of the vitamin C-treated side was seen in the decreased photoaging scores of the cheeks (P = 0.006) and the peri-oral area (P = 0.01). The peri-orbital area improved bilaterally, probably indicating improved hydration. The overall facial improvement of the vitamin C side was statistically significant (P = 0.01). Biopsies showed increased Grenz zone collagen, as well as increased staining for mRNA for type I collagen. No patients were found to have any evidence of inflammation. Hydration was improved bilaterally. Four patients felt that the vitamin C-treated side improved unilaterally. No patient felt the placebo side showed unilateral improvement.
This formulation of vitamin C results in clinically visible and statistically significant improvement in wrinkling when used topically for 12 weeks. This clinical improvement correlates with biopsy evidence of new collagen formation.
Vitamin C is known for its antioxidant potential and activity in the collagen biosynthetic pathway. Photoprotective properties of topically applied vitamin C have also been demonstrated, placing this molecule as a potential candidate for use in the prevention and treatment of skin ageing.
A topically applied cream containing 5% vitamin C and its excipient were tested on healthy female volunteers presenting with photoaged skin on their low-neck and arms in view to evaluate efficacy and safety of such treatment. A double-blind, randomized trial was performed over a 6-month period, comparing the action of the vitamin C cream vs. excipient on photoaged skin. Clinical assessments included evaluation at the beginning and after 3 and 6 months of daily treatment. They were performed by the investigator and compared with the volunteer self assessment. Skin relief parameters were determined on silicone rubber replicas performed at the same time-points. Cutaneous biopsies were obtained at the end of the trial and investigated using immunohistochemistry and electron microscopy. Clinical examination by a dermatologist as well as self-assessment by the volunteers disclosed a significant improvement, in terms of the ‘global score’, on the vitamin C-treated side compared with the control. A highly significant increase in the density of skin microrelief and a decrease of the deep furrows were demonstrated. Ultrastructural evidence of the elastic tissue repair was also obtained and well corroborated the favorable results of the clinical and skin surface examinations.
Topical application of 5% vitamin C cream was an effective and well-tolerated treatment. It led to a clinically apparent improvement of the photodamaged skin and induced modifications of skin relief and ultrastructure, suggesting a positive influence of topical vitamin C on parameters characteristic for sun-induced skin ageing.
Dysfunctional endothelium caused by oxidative stress is thought to play a role in pathogenesis of a variety of conditions including atherosclerosis. We investigated whether a microcirculatory disturbance in hemodialysis (HD) patients was associated with increased oxidative stress and endothelial injury.
Transcutaneous oxygen tension (TcPO2) on the dorsum of the foot at rest was measured as a marker of microcirculation in 33 patients undergoing HD without clinical manifestations of peripheral arterial disease and 20 healthy controls. Furthermore, in order to examine whether TcPO2 was affected by antioxidants, oral supplementation with a combination of vitamin C (200 mg daily) and vitamin E (600 mg daily) was administered for 6 months to 8 patients with microcirculatory disturbance (TcPO2 values of 50 mmHg or less). Serum biochemical parameters including vitamins were also measured.
Mean TcPO2 value was significantly lower in HD patients than in control subjects (47.9 +/- 13.5 mmHg versus 62.4 +/- 11.9 mmHg, p < 0.001). After vitamin supplementation, TcPO2 values remarkably increased (40.6 +/- 10.0 mmHg versus 57.4 +/- 6.5 mmHg, p < 0.005). Serum vitamin C and vitamin E levels increased significantly as well, while serum levels of thrombomodulin, a marker of endothelial injury, and thiobarbituric acid reactants, a marker of lipid peroxidation, were significantly decreased in comparison with those before supplementation.
Our results suggest that the microcirculatory disturbance in HD patients seems to be associated with endothelial damage caused by oxidative stress. Combined supplementation with vitamin C and vitamin E may be of clinical benefit in improving the cutaneous microcirculation by reducing oxidative stress.
Cutaneous hyperpigmentation occurs in multiple conditions. There is a strong need for the improvement of hyperpigmentation especially among Asian women. However, the effect of existing skin-lightening agents is not sufficient. One reason attributes to the limited capability of active agents to be delivered transepidermally. Ultrasound is one promising approach to enhance transepidermal transport. In this work, we investigate the effect of the use of high-frequency ultrasound together with coupling gel containing skin-lightening agents (ascorbyl glucoside and niacinamide) on facial hyperpigmentation in vivo in Japanese women.
The effect of ultrasound on the absorption of skin-lightening agents into the stratum corneum was evaluated in a tape-stripping method on human forearms in vivo. The skin efficacy was assessed in a facial clinical trial involving 60 subjects with hyperpigmentation in a paired design. Subjects were assigned to two groups, each group using two treatments (one on each facial cheek): (1) skin-lightening gel with ultrasound vs. no treatment or (2) skin-lightening gel with ultrasound vs. skin-lightening gel treatment. Changes in facial hyperpigmentation were objectively quantified by computer analysis and visual grading of high-resolution digital images of the face in addition to the subjective assessment via questionnaire.
Ultrasound radiation enhanced the absorption of skin-lightening agents in the stratum corneum in a radiation-time-dependent manner. In the facial clinical trial, use of ultrasound radiation together with the skin-lightening gel significantly reduced facial hyperpigmented spots compared with both no treatment and skin-lightening gel alone after 4 weeks.
The data suggest that use of high-frequency ultrasound radiation together with skin-lightening gel is effective to reduce hyperpigmentation via enhancing transepidermal transport of skin-lightening agents.
Naturally occurring antioxidants were used to regulate the skin damage caused by ultraviolet (UV) radiation because several antioxidants have demonstrated that they can inhibit wrinkle formation through prevention of matrix metalloproteinases (MMPs) and/or increase of collagen synthesis.
We examined the effect of oral administration of the antioxidant mixture of vitamin C, vitamin E, pycnogenol, and evening primrose oil on UVB-induced wrinkle formation. In addition, we investigated the possible molecular mechanism of photoprotection against UVB through inhibition of collagen-degrading MMP activity or through enhancement of procollagen synthesis in mouse dorsal skin.
Female SKH-1 hairless mice were orally administrated the antioxidant mixture (test group) or vehicle (control group) for 10 weeks with UVB irradiation three times a week. The intensity of irradiation was gradually increased from 30 to 180 mJ/cm2. Microtopographic and histological assessment of the dorsal skins was carried out at the end of 10 weeks to evaluate wrinkle formation. Western blot analysis and EMSA were also carried out to investigate the changes in the balance of collagen synthesis and collagen degradation.
Our antioxidant mixture significantly reduced UVB-induced wrinkle formation, accompanied by significant reduction of epidermal thickness, and UVB-induced hyperplasia, acanthosis, and hyperkeratosis. This antioxidant mixture significantly prevented the UVB-induced expressions of MMPs, mitogen-activated protein (MAP) kinase, and activation of activator protein (AP)-1 transcriptional factor in addition to enhanced type I procollagen and transforming growth factor-beta2 (TGF-beta2) expression.
Oral administration of the antioxidant mixture significantly inhibited wrinkle formation caused by chronic UVB irradiation through significant inhibition of UVB-induced MMP activity accompanied by enhancement of collagen synthesis.
Quantification of erythema and pigmentation is useful for analysis of skin tests and management of skin diseases. However, reflectance instruments for this purpose suffer from many technical and financial disadvantages. The aim of this study was to establish a method for evaluation of the amounts of haemoglobin and melanin using ordinary digital cameras and Image J freeware.
Based on the theories on the absorbance of a multilayered skin model, the erythema index (EI) and melanin index (MI) images were derived by image processing from digital colour images of the skin, which were obtained with four kinds of digital cameras. The specificity of these indices and the linearity between index values and the amounts of haemoglobin and melanin were determined by using images of various concentrations of haemoglobin and melanin solutions. The accuracy of both types of index images was also examined by comparing the index values of UV-induced erythema and pigmentation of various intensities with those measured with a reflectance spectrophotometer.
The specificity of EI and MI images was good as little interference was noted with each other. The linearity between EI and haemoglobin concentration, as well as that between MI and melanin concentration was excellent. For UV-induced erythema and pigmentation, good linear correlation was confirmed between two types of EI obtained by the two methods, as well as between two types of MI. However, the index values derived from digital images depended on the camera used as well as on the circumstantial conditions, such as the distance from objects and illumination.
EI and MI images are reliable and useful for quantifying erythema and pigmentation, if obtained under constant and consistent conditions. Apart from financial benefits, this method has many advantages and greater clinical utility in comparison with reflectance instruments.
Dark circles of the lower eyelid (DCLE) represent a well-known beauty problem. The pathogenesis of DCLE is obscure, although stasis and hyperpigmentation of the eyelids have been considered to be involved. One reason for the small number of studies on DCLE may be the difficulty in measuring such soft and curved skin as the eyelids using bulky reflectance meters. The purpose of this study was to quantitatively analyze DCLE using various bioengineering methods.
The lower eyelid and cheek areas of 14 subjects with DCLE and 28 without DCLE were examined using two kinds of reflectance meters and image analysis to measure erythema index (EI), melanin index (MI), and oxygenation index (OX). Ultrasound echo images were also recorded to evaluate the thickness and echo density of the dermis. An in vitro model using collagen gel and hemoglobin solution was also examined as a phantom of eyelid skin.
When contact-type reflectance meters were used, no significant differences in EI, MI, and OX were found between groups with and without DCLE. However, mean values of both MI and EI at eyelids were significantly higher in subjects with DCLE on image analysis, paralleling the results of inspection. Mean dermal thickness was significantly smaller in subjects with DCLE.
Evaluation of EI and MI by image processing methods seems suitable for quantitative evaluation of DCLE, since inadequate contact of the measuring head with the skin is avoided. Whether stasis or hyperpigmentation is more responsible for DCLE remains uncertain. Dermal thickness of eyelid skin may be involved in the appearance of DCLE.
Eye area problems puffiness, bags, dark circles and crowsfeet
- C Oresajo
- M Dickens
- A Znaiden
Oresajo C, Dickens M, Znaiden A. Eye area problems puffiness, bags, dark circles and crowsfeet. Cosmetics Toiletries 1987; 102: 29–34.
Ultrasound: applications in the study of human skin disorders and the response to treatment
- H Schatz
- T Stoudemayer
- Kligman
- A Peter
- G Stephan
- Klaus
Schatz H, Stoudemayer T, Kligman AM. Ultrasound: applications in the study of human skin disorders and the response to treatment. In: Peter A, Stephan G, Klaus H, eds Ultrasound in dermatology. Springer-Verlag New York, NY, 1992: 256–263.
UVA-induced autocrine stimulation of fibroblast-derived-collagenase by IL-6: a possible mechanism in dermal photodamage?
- M Wlaschek
- K Bolsen
- G Herrmann
- A Schwartz
- F Wilmorth
- P C Heinrich
- G Goerz
- K Scharffertter-Kochanek
Evaluation of dark circles of the lower eyelid
- Ohshima H
Eye area problems puffiness, bags, dark circles and crowsfeet
- Oresajo C