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The Effects of Aptamin® Mist on Skin Barrier Function, Skin Hydration, Pruritus VAS, and SCORAD Index in Mild Atopic Dermatitis
... Aptamin C is a substance that combines vitamin C with an aptamer, a DNA fragment that binds specifically to vitamin C. Vitamin C-specific aptamers enhance the stability of vitamin C by preventing its rapid oxidation through interactions with oxygen or aqueous solutions [44]. Moreover, Aptamin C increases skin moisturization and improves pruritus [30]; it also showed a neuroprotective effect in an animal model of Parkinson's disease induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) [23]. The development and progression of skin diseases, including AD and psoriasis, are closely associated with ROS-mediated immune responses, and the antioxidant vitamin C is an effective anti-inflammatory molecule, because it acts as an ROS scavenger [45]. ...
Atopic dermatitis (AD), a chronic inflammatory skin disease, is characterized by eczemous lesions on the skin that manifest as severe itching and last a long time. AD is thought to be a response to local allergens, including house dust mites (HDMs). Aptamin C is a modified form of vitamin C comprised of aptamers (DNA fragments) that bind specifically to vitamin C and inhibit its oxidation, thereby increasing its stability and antioxidant effects. It is already known that vitamin C shows an anti-inflammatory effect on skin inflammation. Oxidative stress is one of the major causes of inflammatory diseases, including HDM-induced skin inflammation, suggesting that the antioxidant activity of Aptamin C could regulate inflammatory responses to HDMs in the skin keratinocyte cell line HaCaT and primary skin keratinocytes. Aptamin C not only inhibited HDM-induced proliferation of both type of cells, but suppressed HDM-induced increases in interleukin (IL)-1α and IL-6 production by these cells. In addition, Aptamin C suppressed the production of IL-17 and IL-22 by T cells, which are closely associated with AD pathogenesis, as well as HDM-induced IL-22Rα expression. Aptamin C also reduced the production of thymus and activation-regulated chemokine (TARC) by suppressing the interaction between IL-22 and IL-22Rα, as well as reducing T cell migration. Although HDM treatment markedly increased the expression of glial cell line-derived neurotrophic factor (GDNF), which is associated with itching in AD skin lesions, this increase was reduced by Aptamin C treatment. Taken together, these results suggest that Aptamin C can effectively regulate inflammatory lesions, such as AD, by regulating the production of inflammatory cytokines and GDNF induced by HDM.
Dr Anne-Claire Fougerousse is Head of Dermatology at the Bégin Hospital in Saint-Mandé, France, and scientific coordinator of a French network of dermatologists and allergists (ResoEczema). The focus of her work is to improve the care of adolescent and adult patients with atopic dermatitis (AD), a chronic, pruritic inflammatory skin disease that substantially impacts patient quality of life. In this interview, Dr Fougerousse provides an overview of the clinical presentation of adult patients with AD and describes available treatments. Today, topical agents like emollients and corticosteroids are the mainstay of AD therapy, and patients with lesions that are resistant to optimally administered topical treatment can also receive phototherapy or systemic therapy with ciclosporin. Dr Fougerousse discusses her hopes for the future of AD therapy with the recent development of biologicals like dupilumab, which may provide improvements in clinical outcomes and quality of life for patients with moderate-to-severe AD. In the next few years, the therapeutic arsenal for AD will likely expand to include more systemic therapies providing sustained symptom control. The real challenge will be to ensure that the maximum number of patients with AD achieve clinical benefits from these new treatments.
Background:
Vitamin C (also known as L-ascorbic acid) plays a critical role in reactive oxygen species (ROS) reduction and cell regeneration by protecting cell from oxidative stress. Although vitamin C is widely used in cosmetic and therapeutic markets, there is considerable evidence that vitamin C easily undergoes oxidation by air, pH, temperature, and UV light upon storage. This deficiency of vitamin C decreases its potency as an antioxidant and reduces the shelf-life of products containing vitamin C as its ingredient. To overcome the deficiency of vitamin C, we have developed Aptamin C, an innovative DNA aptamer maximizing the antioxidant efficacy of vitamin C by binding to the reduced form of vitamin C and delaying its oxidation.
Methods:
Binding of Aptamin C with vitamin C was determined using ITC analysis. ITC experiment was performed 0.2 mmol/L vitamin C that was injected 25 times in 2 µL aliquots into the 1.8 mL sample cell containing the Aptamin C at a concentration of 0.02 mmol/L. The data were fitted to a one-site binding isotherm using with origin program for ITC v.5.0.
Results:
To investigate the effect of Aptamin C and vitamin C complex in human skins, both in vitro and clinical tests were performed. We observed that the complex of Aptamin C and vitamin C was significantly effective in wrinkle improvement, whitening effect, and hydration increase. In the clinical test, subjects treated with the complex showed dramatic improvement in skin irritation and itching. No adverse reaction was presented by Aptamin C complex in the test.
Conclusion:
Taken together, these results showed that Aptamin C, an innovative novel compound, should potentially be served as a key cosmeceutical ingredient for a range of skin conditions.
The outermost layer of the skin, the stratum corneum , is essential for the protective barrier functions of the skin. It results from the stacking of corneocytes, the dead flattened cells resulting from epidermal terminal differentiation of underlying living keratinocytes. The cornified lipid envelope, encapsulating corneocytes, and the extracellular mortar-like multilayered lipid matrix, called lamellae , are two crucial elements of the epidermal barrier. Stratum corneum extracellular lipids are mainly composed of ceramides, cholesterol and free fatty acids. Ceramides, and more specifically the epidermis specific ω-O-acylceramides, are essential for lipid-matrix organization into lamellae and formation of the corneocyte lipid envelope. Pathophysiological studies of inherited lipid metabolism disorders recently contributed to a better understanding of stratum corneum lipid metabolism. In the lab, our data from patients with Autosomal Recessive Congenital Ichthyosis and a murine knock-out model showed that the enzyme PNPLA1 is essential for the last step of synthesis of omega-O-acylceramides. Skin aging is a complex biological process caused by genetic and extrinsic factors e.g. sun exposure, smoke, and pollution. Aging skin is marked by a senescence-related decline in lipid and water content, which ultimately impairs epidermal barrier function. Thus, aged epidermis is prone to develop altered drug permeability, increased susceptibility to irritants contact dermatitis and severe xerosis. Ceramide deficiency may account, at least in part, for the dysfunction of the stratum corneum associated with ageing. Hence, treatments able to increase skin-ceramide levels could improve the epidermal barrier function in aged skin. Many animal testing and clinical trials are taken in that regard.
Vitamin C (ascorbic acid) is not only commercially available as a nutritionally important dietary supplement, but is also used as a stabilizer in a wide range of other products, including beverages, cosmetics and therapeu-tics, because of its antioxidant properties. However, vitamin C itself undergoes oxidation upon storage, which decreases its efficacy as a stabilizer of other materials and also significantly reduces the shelf-life of products containing it as an active ingredient. Protecting such formulations and products against oxidation-induced degradation would thus be valuable. Here, we report the development of a new DNA aptamer that decreases the rate of oxidation of vitamin C in aqueous solution. We found that the presence of this aptamer reduced the rate of CuSO 4-stimulated oxidation of vitamin C by more than 50% in aqueous solution. Furthermore, we also found that the aptamer increased the half-life of vitamin C by up to 1.7-fold in certain commercially available vitamin water formulations. This is the first description of aptamer-based stabilization of a commercially important substance and has significant implications for multiple industries.
Moisturizer is a major component of basic daily skin care, particularly in presence of epidermal barrier alteration and reduced epidermal water content. It is an important part of a dermatologist's strategy to maintain skin health as well as treating various dermatoses which co-exist with skin dryness, linked to impaired skin barrier function such as in atopic disorder as well as other types of dermatitis. Mastering the knowledge regarding action mechanism, application, dosage, adverse effects as well as specific clinical usage of moisturizers is must for a dermatologist, in order to support the capability to recommend their use, particularly for therapeutic purposes, in accordance with evidence-based medicine. This review is aimed to discuss the use of moisturizer both as skin health maintenance as well as a definitive or adjuvant therapy, particularly for many kinds of dermatitis.
Atopic dermatitis (AD) is a common chronic skin inflammatory disorder characterized by recurrent eczema accompanied by an intractable itch that leads to an impaired quality of life. Extensive recent studies have shed light on the multifaceted pathogenesis of the disease. The complex interplay among skin barrier deficiency, immunological derangement, and pruritus contributes to the development, progression, and chronicity of the disease. Abnormalities in filaggrin, other stratum corneum constituents, and tight junctions induce and/or promote skin inflammation. This inflammation, in turn, can further deteriorate the barrier function by downregulating a myriad of essential barrier-maintaining molecules. Pruritus in AD, which may be due to hyperinnervation of the epidermis, increases pruritogens, and central sensitization compromises the skin integrity and promotes inflammation. There are unmet needs in the treatment of AD. Based on the detailed evidence available to date, certain disease mechanisms can be chosen as treatment targets. Numerous clinical trials of biological agents are currently being conducted and are expected to provide treatments for patients suffering from AD in the future. This review summarizes the etiopathogenesis of the disease and provides a rationale for choosing the novel targeted therapy that will be available in the future.
Background:
Guidelines discourage the use of systemic corticosteroids for atopic dermatitis but their use remains widespread.
Objective:
To reach consensus among an international group of atopic dermatitis experts on the use of systemic corticosteroids for atopic dermatitis.
Methods:
A survey consisting of statements accompanied by visual analog scales ranging from "strongly disagree" to "neutral" to "strongly agree" was distributed to the International Eczema Council (IEC). Consensus was reached in agreement on a statement if <30% of respondents marked to the left of "neutral" towards "strongly disagree."
Results:
Sixty of 77 (79%) IEC members participated. Consensus was reached on 12 statements, including that systemic corticosteroids should generally be avoided but can be used rarely for severe atopic dermatitis under certain circumstances, including a lack of other treatment options, as a bridge to other systemic therapies or phototherapy, during acute flares in need of immediate relief, in anticipation of a major life event or in the most severe cases. If used, treatment should be limited to short-term. Most respondents agreed that systemic corticosteroids should never be used in children, but consensus was not reached on that statement. The conclusions of our expert group are limited by a dearth of high-quality published evidence. If more stringent consensus criteria were applied (e.g., requiring <20% of respondents marking towards "strongly disagree," consensus would have been reached on fewer statements.
Conclusions:
Based on expert opinion from the IEC, routine use of systemic corticosteroids for atopic dermatitis is generally discouraged and should be reserved for special circumstances. This article is protected by copyright. All rights reserved.
Background
Obesity is well associated as being an interfering factor in metabolic diseases such as hypertension and diabetes by increasing the secretion of proinflammatory markers from adipose tissue. Having healthy effects, vitamin C could work as an anti-inflammatory agent through its antioxidant capacity.
Registration
Registration number: FPSK_Mac [13]04.
Objective
The aim of the study reported here was to identify the effect of vitamin C on reducing the levels of inflammatory markers in hypertensive and/or diabetic obese adults.
Subjects and methods
Sixty-four obese patients, who were hypertensive and/or diabetic and had high levels of inflammatory markers, from primary health care centers in Gaza City, Palestine, were enrolled into one of two groups in an open-label, parallel, randomized controlled trial. A total of 33 patients were randomized into a control group and 31 patients were randomized into an experimental group. The experimental group was treated with 500 mg vitamin C twice a day.
Results
In the experimental group, vitamin C significantly reduced the levels of high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), fasting blood glucose (FBG), and triglyceride (TG) after 8 weeks of treatment (overall: P<0.001); no changes appeared in total cholesterol (TC). In the control group, there were significant reductions in FBG and TG (P=0.001 and P=0.026, respectively), and no changes in hs-CRP, IL-6, or TC. On comparing the changes in the experimental group with those in the control group at the endpoint, vitamin C was found to have achieved clinical significance in treating effectiveness for reducing hs-CRP, IL-6, and FBG levels (P=0.01, P=0.001, and P<0.001, respectively), but no significant changes in TC or TG were found.
Conclusion
Vitamin C (500 mg twice daily) has potential effects in alleviating inflammatory status by reducing hs-CRP, IL-6, and FBG in hypertensive and/or diabetic obese patients.
Loss-of-function mutations in the skin barrier protein filaggrin (FLG) are a major risk for atopic dermatitis (AD). The pathogenic sequence of disturbances in skin barrier function before or during the early development of AD is not fully understood. A more detailed understanding of these events is needed to develop a clearer picture of disease pathogenesis. A robust, noninvasive test to identify babies at high risk of AD would be important in planning early intervention and/or prevention studies.
To ascertain whether a noninvasive measurement of skin barrier function at day 2 after birth and at 2 months predicts the development of AD at 1 year. Furthermore, to determine whether increases in transepidermal water loss (TEWL) predate the development of clinical AD.
A total of 1903 infants were enrolled in the Cork Babies After Scope: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints Birth Cohort study from July 2009 to October 2011. Measurements of TEWL were made at birth (day 2) and at 2 and 6 months. The presence of AD was ascertained at 6 and 12 months, and disease severity was assessed by using the SCORing Atopic Dermatitis clinical tool at 6 months and by using both the SCORing Atopic Dermatitis clinical tool and Nottingham Severity Score at 12 months. A total of 1300 infants were genotyped for FLG mutations.
At 6 months, 18.7% of the children had AD, and at 12 months, 15.53%. In a logistic regression model, day 2 upper quartile TEWL measurement was significantly predictive of AD at 12 months (area under the receiver operating characteristic curve, 0.81; P < .05). Lowest quartile day 2 TEWL was protective against AD at 12 months. An upper quartile 2 month TEWL was also strongly predictive of AD at 12 months (area under the receiver operating characteristic curve, 0.84; P < .05). At both ages, this effect was independent of parental atopy, FLG status, or report of an itchy flexural rash at 2 months. Associations were increased when parental atopy status or child FLG mutation status was added into the linear regression model.
Impairment of skin barrier function at birth and at 2 months precedes clinical AD. In addition to providing important mechanistic insights into disease pathogenesis, these findings have implications for the optimal timing of interventions for the prevention of AD.
Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Atopic dermatitis (AD) is the most common chronic inflammatory skin disorder. The disease is typified by chronic pruritus, a series of signs and symptoms associated with immune dysfunction (eg, increased immunoglobulin E mediated allergies), and abnormal skin barrier dysfunction (eg, increased response to irritants). Due to the chronic itch and reactivity, patients and parents of affected children will seek therapy. Therapies range from emollients to topical medicaments, including topical corticosteroids, and immunosuppressive agents. Due to concerns about the side effects of the available agents, patients and their loved ones will often seek "natural" agents as therapy. Oral agents that have been tried in (AD) include probiotics, vitamins, oils, and such traditional therapeutics as Chinese herbals and Ayurvedic agents. At this time probiotics may be promising, but there are inadequate data to determine their efficacy. In addition, there are significant concerns for the risks associated with Chinese herbals, which may be associated with liver failure and death, and Ayurvedic agents, which may be tainted with heavy metals. The safest and most effective natural agents are topically applied emollients.
The skin consists of the epidermis, dermis and subcutis. The epidermis is primarily comprised of keratinocytes and is separated into four layers according to the stage of differentiation of the keratinocytes. Corneocytes are terminally differentiated keratinocytes that closely interact with other corneocytes through corneodesmosomes, and synthesize lamellar bodies and the intercellular multilamellar barrier, which protects the body from the external environment. As ceramides are the principal components of lamellar bodies and the multilamellar barrier, it is important to understand the biosynthesis of ceramides and their functions in skin. Ceramides are synthesized by amide bond‑mediated interactions between sphingoid bases, long‑chain amino alcohols [long-chain base] and fatty acids through a de novo pathway, a sphingomyelin (SM) hydrolysis pathway and a catabolic pathway. The majority of ceramides produced by the de novo pathway form the epidermal barrier. Ceramides used as signaling molecules are synthesized by the SM and catabolic pathways. Synthesized ceramides are released from corneocytes and form the multilamellar barrier. Additionally, ceramides and their metabolites regulate the apoptosis, proliferation and differentiation of skin cells as well as the formation of the skin barrier. Thus, the study of ceramides and their metabolites is crucial to understanding the function and regulation of the skin barrier.
Atopic dermatitis is a common and chronic, pruritic inflammatory skin condition that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this second of 4 sections, treatment of atopic dermatitis with nonpharmacologic interventions and pharmacologic topical therapies are reviewed. Where possible, suggestions on dosing and monitoring are given based on available evidence.
Atopic dermatitis (AD) is a chronic inflammatory skin condition with complex etiology that is dependent upon interactions between the host and the environment. Acute skin lesions exhibit the features of a Th2-driven inflammatory disorder, and many patients are highly atopic. The skin barrier plays key roles in immune surveillance and homeostasis, and in preventing penetration of microbial products and allergens. Defects that compromise the structural integrity or else the immune function of the skin barrier play a pivotal role in the pathogenesis of AD. This article provides an overview of the array of molecular building blocks that are essential to maintaining healthy skin. The basis for structural defects in the skin is discussed in relation to AD, with an emphasis on filaggrin and its genetic underpinnings. Aspects of innate immunity, including the role of antimicrobial peptides and proteases, are also discussed.
Improving skin barrier function and moisturizing without irritation are important components of managing patients with atopic dermatitis. This study evaluated the safety and tolerability of a body wash and moisturizer regimen for infants and toddlers with atopic dermatitis. This was an open-label study involving 56 children (3-36 months old) with a history of atopic dermatitis. The skin care regimen (Cetaphil Restoraderm Skin Restoring Body Wash and Cetaphil Restoraderm Skin Restoring Moisturizer; Galderma Laboratories, L.P.) was used at least once daily, but no more than twice daily, for 4 weeks. The primary variable of interest was the worst postbaseline scores for local tolerability (expressed as success or failure) using a 4-point scale for each component (erythema, edema, scaling and dryness, rash, and signs of discomfort upon application). Assessments of moisture content of the stratum corneum and transepidermal water loss were also performed. Fifty-three children completed the study. The percentage of subjects with no erythema increased from 33.9% to 50.0% by Week 4. The percentage of subjects with no scaling or dryness increased from 58.9% to 85.2% at Week 4. A statistically significant increase in corneometry from baseline (p < 0.001) and a statistically significant decrease in transepidermal water loss (p = .009) were observed. The body wash and moisturizer regimen was safe and well tolerated and improved hydration and skin barrier function in infants and toddlers as young as 3 months of age with a history of atopic dermatitis.
Moisturizers result in an increase of skin hydration and restoration of the skin barrier function and play a prominent role in the longterm management of atopic dermatitis (AD). Cetaphil RestoradermTM Moisturizer (CRM) contains novel ingredients specifically designed for AD, and its effects on skin hydration, skin barrier function and signs of AD were assessed in four studies, three of which were evaluator-blinded, randomized and intra-individual comparison trials. A single application of CRM induced significantly greater hydration than the untreated control for at least 24 hours (P is less than 0.001). After the skin was disrupted with 0.5% sodium dodecyl sulfate (SDS), applications of CRM led to a more rapid restoration of skin barrier function and maintained significantly greater skin hydration compared to the untreated control (both P is less than 0.05). After four weeks of twice-daily CRM application among subjects with a history of AD, a significant decrease of itching/stinging scores compared to baseline was reported, as well as an improvement in the quality-of- life and a high level of satisfaction regarding the product. When CRM was used as an adjunctive treatment with topical steroid for four weeks among subjects with mild-to-moderate AD, a more rapid decrease of overall disease severity was observed on days 7, 14 and 21 by the blinded investigator (P is less than 0.05), compared to steroid treatment alone. In summary, CRM is suitable for the specific needs of patients with AD and can be used either alone for long-term management or in adjunction with traditional treatment for both short and long-term disease control.
Atopic dermatitis (AD) is a common, chronically recurring skin disorder. Dry skin is a common finding in patients with AD, apart from the dermatitis. Although there are obvious clinical signs of an impaired barrier function of the skin, few investigators have studied this aspect of AD. The stratum corneum, where the barrier is located, has been studied with different techniques in patients with AD, and the results are now presented. The water-binding capacity of dry atopic skin was found to be reduced when measured with an in vitro microbalance technique. TEWL (transepidermal water loss) measured with and Evaporimeter Ep1, was increased in dry skin and in clinically normal skin of atopics on predilection areas. Water content was decreased in dry atopic skin, when measured with the Corneometer CM 420. In a quantitative electron microscopic study, the lamellar bodies were found to have an increased relative volume in dry atopic skin. When using chromatographic analysis, preliminary data suggested reduced amounts of extractable stratum corneum lipids in patients with AD. In a clinical study, 80% of the patients with AD regarded their skin as being dry. Fifty percent were found to have areas of dry skin, on clinical examination. By scanning electron microscopy (SEM), the surface pattern of dry atopic skin was found to be coarse and irregular. When using profilometry, quantitative differences in roughness parameters were found in dry atopic vis-à-vis to normal skin.(ABSTRACT TRUNCATED AT 250 WORDS)
Renewed interest in the antihistamine action of ascorbic acid has emerged with the recently recognized immunosuppressive role of histamine. We examined the antihistamine effect of acute and chronic vitamin C (VC) administration and its effect on neutrophil chemotaxis in healthy men and women. In the chronic study, 10 subjects ingested a placebo during weeks 1, 2, 5 and 6, and 2 g/day of VC during weeks 3 and 4. Fasting blood samples were collected after the initial 2-week period (baseline) and at the end of weeks 4 and 6. Plasma ascorbate rose significantly following VC administration compared to baseline and withdrawal values. Neutrophil chemotaxis rose 19% (NS) during VC administration, and fell 30% after VC withdrawal, but these changes were not correlated to plasma ascorbate levels (r = 0.01). Chemotaxis was inversely correlated to blood histamine (r = -0.32, p = 0.045), and, compared to baseline and withdrawal values, histamine levels were depressed 38% following VC supplementation. Blood histamine and neutrophil chemotaxis did not change 4 hours following a single 2 g dose of ascorbic acid, although plasma ascorbate rose 150%. These data indicate that VC may indirectly enhance chemotaxis by detoxifying histamine in vivo.
- S F Thomsen
Thomsen SF (2014) Atopic Dermatitis: Natural History,
Diagnosis, and Treatment 2014: 354250.