Background While increased levels of circulating inflammatory cytokines in chronologically aged humans have been linked to the development of ageing‐associated chronic disorders (e.g., cardiovascular disease, type II diabetes, osteoporosis and Alzheimer's disease), approaches that reduce circulating cytokines are not yet available. In chronologically aged mice, we recently demonstrated that epidermal dysfunction largely accounts for age‐associated elevations in circulating cytokine levels, and that improving epidermal function reduced circulating cytokine levels. Objective We performed a pilot study to determine whether improving epidermal function reduces circulating pro‐inflammatory cytokine levels in aged humans. Methods Thirty‐three aged humans were topically treated twice‐daily for 30 days, with ≈ 3 mL of an emollient, previously shown to improve epidermal function, while untreated, aged humans and a cohort of young volunteers served as controls. Changes in epidermal function and levels of three key, age‐related, plasma cytokines (IL‐1β, IL‐6 and TNFα) were measured at baseline and after treatment, using Luminex 200™ system. Results We also found significantly higher baseline levels of IL‐1β, IL‐6 and TNFα in aged vs. young humans (P < 0.001), as previously reported. Topical applications of the barrier repair emollient significantly enhanced epidermal permeability barrier function (P < 0.01) and stratum corneum hydration (P < 0.05). In parallel, circulating levels of IL‐1β and IL‐6 normalized, while TNFα levels declined substantially. Conclusion The results of this preliminary study suggest that a larger clinical trial should be performed to confirm whether improving epidermal function also can reduce circulating pro‐inflammatory cytokine levels in aged humans, while also possibly attenuating the downstream development of chronic inflammatory disorders in the aged humans.
Mutations in several lipid synthetic enzymes that block fatty acid and ceramide production produce autosomal recessive congenital ichthyoses (ARCIs) and associated abnormalities in permeability barrier homeostasis. However, the basis for the phenotype in patients with NIPAL4 (ichthyin) mutations (among the most prevalent ARCIs) remains unknown. Barrier function was abnormal in an index patient and in canines with homozygous NIPAL4 mutations, attributable to extensive membrane stripping, likely from detergent effects of nonesterified free fatty acid. Cytotoxicity compromised not only lamellar body secretion but also formation of the corneocyte lipid envelope (CLE) and attenuation of the cornified envelope (CE), consistent with a previously unrecognized, scaffold function of the CLE. Together, these abnormalities result in failure to form normal lamellar bilayers, accounting for the permeability barrier abnormality and clinical phenotype in NIPA-like domain-containing 4 (NIPAL4) deficiency. Thus, NIPAL4 deficiency represents another lipid synthetic ARCI that converges on the CLE (and CE), compromising their putative scaffold function. However, the clinical phenotype only partially improved after normalization of CLE and CE structure with topical ω-O-acylceramide because of ongoing accumulation of toxic metabolites, further evidence that proximal, cytotoxic metabolites contribute to disease pathogenesis.
The dermal-epidermal junction (DEJ) provides a physical and biological interface between the epidermis and the dermis. In addition to providing a structural integrity, the DEJ also acts as a passageway for molecular transport. Based on the recently reported importance of the DEJ in skin aging, novel peptide derivatives have been tested for their effects on basement membrane (BM) protein expressions in cultured human epidermal keratinocytes. As a result, protein expressions of collagen XVII, laminin and nidogen were stimulated by the test peptide and peptides complex. Further ex vivo evaluation using excised human skin, confirmed that the topical application of the peptides complex significantly increased dermal collagen expression, as well as expressions of collagen XVII and laminin. Interestingly, while the origin of the laminin protein is epidermal keratinocytes, the immunohistochemical staining of skin showed that laminin was only detected in the uppermost layer of the dermis, which suggests a tight assembly of laminin protein onto the dermal side of the DEJ. These results suggest that a peptide complex could improve the structural properties of the DEJ through its ability to stimulate BM proteins. In order to evaluate the anti-wrinkle benefits of the peptide complex in vivo, a clinical study was performed on 22 healthy Asian female volunteers older than 40 years. As a result, significant improvements in skin wrinkles for all of the five sites were observed after two weeks, as assessed by skin topographic measurements. Collectively, these results demonstrate the anti-aging efficacy of the peptides complex.
IntroductionThe management of sensitive skin, which affects over 60% of the general population, has been a long-standing challenge for both patients and clinicians. Because defective epidermal permeability barrier is one of the clinical features of sensitive skin, barrier-enhancing products could be an optimal regimen for sensitive skin. In the present study, we evaluated the efficacy and safety of two barrier-enhancing products, i.e., Atopalm® Multi-Lamellar Emulsion (MLE) Cream and Physiogel® Intensive Cream for sensitive skin.Methods60 patients with sensitive skin, aged 22–40 years old, were randomly assigned to one group treated with Atopalm MLE Cream, and another group treated with Physiogel Intensive Cream twice daily for 4 weeks. Lactic acid stinging test scores (LASTS), stratum hydration (SC) and transepidermal water loss (TEWL) were assessed before, 2 and 4 weeks after the treatment.ResultsAtopalm MLE Cream significantly lowered TEWL after 2 and 4 weeks of treatment (p < 0.01). In contrast, Physiogel Intensive Cream significantly increased TEWL after 2 weeks of treatment (p < 0.05) while TEWL significantly decreased after 4-week treatments. Moreover, both Atopalm MLE Cream and Physiogel Intensive Cream significantly increased SC hydration, and improved LASTS after 4 weeks of treatment.ConclusionBoth barrier-enhancing products are effective and safe for improving epidermal functions, including permeability barrier, SC hydration and LASTS, in sensitive skin. These products could be a valuable alternative for management of sensitive skin.FundingVeterans Affairs Medical Center, San Francisco, California, USA, and NeoPharm Co., Ltd., Daejeon, Korea.Electronic supplementary materialThe online version of this article (doi:10.1007/s13555-016-0097-6) contains supplementary material, which is available to authorized users.
This study focuses on identifying the CO2 absorption mechanism in an aqueous potassium carbonate (K2CO3)/homopiperazine (homoPZ) solution, at various CO2 loading. 1H nuclear magnetic resonance (NMR) and 13C NMR measurements were conducted at 295 K within the absorbent concentration of homoPZ 7.5 wt % and K2CO3 15 wt %/homoPZ 7.5 wt %. The CO2-loaded absorbents were prepared by using vapor–liquid equilibrium (VLE) apparatus at 333 K. The results show that the amount of carbamate and bicarbamate in the CO2-loaded K2CO3/homoPZ solution was larger than in the homoPZ solution. The free homoPZ that is able to react with CO2 increases in the aqueous K2CO3/homoPZ solution because the K2CO3 serves as a buffer. It was found that the NMR method can be used to determine the CO2 absorption mechanism of the absorbents.
Recently, cannabis, or its major constituent cannabidiol (CBD), has emerged as an attractive cosmetic ingredient. Initiated as a basic investigation of the physiological roles of cannabinoid receptors and their endogenous ligands, endocannabinoids’ diverse potential benefits have been proposed for using cannabinoid receptor modulating compounds in skin health. Improvement in skin barrier functions, alleviating inflammatory responses, and the relief of itching sensations are some commonly expected therapeutic benefits, which have been supported by many in vitro, in vivo, and clinical studies. While hemp seed oils or hemp extracts might be used for the cosmetic formulation, the potential for contamination with a psychoactive cannabinoid, such as 9-THC, should be carefully checked. Instead of using hemp-derived ingredients, the use of cannabinomimetics, synthetic ligands on cannabinoid receptors, or entourage compounds (which modulate intracellular synthesis and the degradation of endocannabinoids), have been tried. In this review, a brief introduction of the epidermal endocannabinoid system (EES) and its physiological roles will be followed by a review of the cosmetic and dermatologic application of cannabinomimetics and entourage compounds. The practical application of newly developed endocannabinomimetics will be discussed as well.
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