Skin Pharmacology and Physiology最新文献

Introduction: Diabetic foot ulcers (DFUs) are a common complication in diabetes, leading to high amputation risk and significant healthcare costs. Given topical timolol's emergence as a potential wound-healing agent, our study explored its impact on epidermal integrity.

Methods: This study was a post hoc analysis conducted as part of a randomized controlled trial at the Veterans Affairs Northern California Health Care System. Twenty patients, who had DFUs healed in the original trial, 10 in the timolol arm, and 10 in the placebo arm, were enrolled in the study. The primary outcome was transepidermal water loss, measured monthly for 3 months of post-healing using a closed-chamber device. The secondary outcome was re-ulceration rates over 1 year.

Results: Transepidermal water loss at 1, 2, and 3 months of post-healing was significantly lower in the timolol group than in the placebo group (p < 0.01). Linear mixed models identified contralateral foot transepidermal water loss as a significant predictor of healed diabetic foot ulcer site transepidermal water loss (estimate = 0.76, p < 0.001). The interaction between timolol treatment and months since healing significantly reduced transepidermal water loss over time (estimate = -2.2, p = 0.002). The use of a wheelchair was also associated with a significant decrease in transepidermal water loss (estimate = -7.7, p = 0.01). Initial transepidermal water loss values were higher in patients who re-ulcerated, but the difference was not statistically significant (p = 0.42). There was no difference in re-ulceration rates in this small pilot study.

Conclusion: Topical timolol significantly improved skin barrier function in healed DFUs, reducing transepidermal water loss. Although re-ulceration rates were not significantly different, the trend suggests potential benefits. Further studies with larger sample sizes and longer follow-up are needed to confirm these findings and explore transepidermal water loss's predictive value for re-ulceration.

Background: Understanding skin aging and developing effective interventions represent fundamental challenges in dermatology. Key mechanisms driving this process include complex interactions among cellular senescence, extracellular matrix remodeling, oxidative stress, and inflammatory networks.

Summary: Recent advances have catalyzed the development of innovative peptide-based therapeutic strategies for skin aging. These include environment-responsive peptides, biomimetic peptides, and advanced nano-delivery systems. The integration of chronobiology and multi-omics analysis further supports the evolution of these approaches.

Key messages: We envision a new era of personalized solutions for skin aging, driven by the convergence of molecular understanding, delivery innovations, and precision medicine. This paradigm shift holds transformative potential not only for dermatology but also for broader aspects of human aging and health.

Background: The major carriers of linoleic acid in the epidermis are an acylglucosylceramide in the viable portion of the epidermis and an analogous acylceramide in the stratum corneum. The acylglucosylceramide and acylceramide are the precursors of the corneocyte lipid envelope (CLE).

Summary: Oxidation of the ester-linked linoleate by two lipoxygenases working in tandem has been shown to be involved in CLE formation. Acylglucosylceramide appears to be the substrate for initial CLE formation at the bottom of the stratum corneum, while acylceramide is the precursor for the covalently attached ω-hydroxyceramide thereafter. It would be expected that consumption of linoleate in CLE formation would decrease the linoleate content of the remaining acylceramide; however, this is not observed for total acylceramide. When acylceramide from only the outer layers of stratum corneum has been analyzed, the linoleate content is notably reduced compared to the values found for these lipids from full thickness stratum corneum or epidermis. This is consistent with a major role for the linoleate-containing acylceramide in the later stages of CLE maturation. This also suggests that a mechanism that is not selective for ester-linked linoleate may also be involved in early CLE formation, while the oxygen-dependent mechanisms are essential in the later stage of envelope maturation.

Key message: This review proposes an oxygen-independent mechanism that may contribute to the early stages of CLE formation. The lipoxygenase-dependent contribution to the formation of the CLE would be more prominent in the later stages of maturation.

Introduction: Changes in the skin microbiome in atopic dermatitis (AD) include a reduced bacterial diversity and increased abundance of Staphylococcus aureus. Topical antibiotics and antiseptics may decrease bacterial pathogens but lack positive effects on microbiome diversity.

Methods: In this double-blind, intraindividual vehicle-controlled proof-of-concept study, n = 20 patients received a gel containing a defined extract (Spiralin®) of the microalgae Spirulina platensis, previously shown to exert anti-microbial effects, or vehicle on target lesions of similar size and clinical activity. The Shannon index reflecting α-diversity and the abundance of S. aureus were calculated from the analysis of 16s rRNA gene libraries with untreated non-lesional skin serving as control. Clinical activity was determined by the Target Lesion Severity Score (TLSS) and lesion size.

Results: Positive effects of the active gel on the microbiome after 4 weeks of treatment were indicated by a significant increase of the Shannon index in areas treated with verum (mean increase 16.7%; p < 0.01 vs. baseline), but not in areas treated with vehicle. This increase in verum-treated lesions was more pronounced in lesions with an at least 50% (26.3%) or an at least 75% reduction of the TLSS (33.3%). There was also a stronger decrease of the abundance of S. aureus in lesions treated with active gel compared to those treated with vehicle (25.5% vs. 9.4%), but significance was not met. There were several trends, indicating clinical effects of the active gel. For example, vehicle-treated areas showed no reduction in area size (77.8 cm2 at week 4 compared to 77.0 cm2 at baseline), while verum-treated lesion area decreased on average by 6.9 cm2. Active and vehicle gel were well tolerated, and very few local side effects were noted.

Conclusion: These preliminary results indicate a positive effect of a gel-containing Spiralin® on the skin microbiome in patients with active AD lesions combined with reductions in clinical disease activity, supporting further investigations of the active gel alone or in combination with anti-inflammatory treatments in larger AD studies.

Background: Alopecia areata (AA) is a T-cell-mediated autoimmune disease that significantly impacts patient quality of life. The breakdown of hair follicle immune privilege underlies AA pathogenesis. However, the precise mechanism of this breakdown remains unclear. This study investigates the potential role of reactive oxygen species in AA pathogenesis.

Summary: A systematic review and meta-analysis were conducted on observational studies and randomized controlled trials from 2000 to 2024. Studies included AA patients and measured oxidative stress index (OSI), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), or paraoxonase-1 (PON1). Extracted data were analyzed using the Cochrane risk-of-bias tool and random-effects models. The review included 21 studies with 743 AA patients. OSI was elevated in AA patients (effect size = 1.58, 95% CI: 0.31-2.68, p = 0.00068). MDA levels were also elevated (effect size = 1.60, 95% CI: 0.43-2.6, p = 0.00023), while SOD (effect size = -0.97, 95% CI: -1.65 to -0.30, p = 0.00066) and GSH-Px (effect size = -1.41, 95% CI: -2.28 to -0.53, p = 0.00068) activities were reduced. PON1 levels showed no significant difference (effect size = -3.56, 95% CI: -8.63 to 1.51, p = 0.051).

Key messages: The elevated OSI and MDA, and decreased antioxidant activity in AA patients suggest a substantial role for reactive oxygen species and oxidative stress in AA pathogenesis, highlighting oxidative stress as a potential target for therapeutic intervention. These results underscore the importance of oxidative stress in AA and support further research into antioxidant-based therapies.

Introduction: Emollients are part of daily body care and have become indispensable therapeutic adjuvants for the treatment of dry skin conditions. Adherence to topical treatments, notably for dry skin conditions, has been reported to be low. The underlying reasons may include insufficient medical and nursing support for product selection, specific product attributes, aspects of product application, and product feel on the skin. Attempts have also been made to portray lipid content, galenic product format, or rheological attributes (pharmaceutical attributes) as adherence-promoting or adherence-preventing properties. In the treatment of dry dermatoses with emollients, there is little information describing and relating to these various features. We explored whether the sensory attributes of selected emollients were associated with common product attributes such as lipid content, viscosity, or galenic product format and discuss the extent to which this information is useful for product selection.

Methods: Nine trained panellists evaluated ten selected emollients based on a set of 18 predefined sensory attributes according to a standard guide for sensory descriptive analysis. Viscosity was determined using a rotational rheometer.

Results: The emollients had product-specific sensory attributes. Lipid content, viscosity, and galenic product format are not generally indicative of sensory product attributes.

Conclusion: Contrary to popular belief, lipid content and viscosity are not generally indicative of sensory product attributes. This is mainly due to the different physicochemical properties of the lipid-phase ingredients, which are product-specific and diverse. As most emollients contain significant amounts of volatile ingredients that evaporate during and after application, their galenic format changes dramatically. Therefore, this is not a viable selection criterion. Because refined information on sensory product attributes, as compiled for this study, is rarely available in everyday life, eliciting individual and subjective patient preferences through dialogue remains crucial. Ideally, patient preferences can be elicited from the sample packs.

Introduction: Previous studies have investigated the density of dermal papillae (DP) in normal skin using reflectance confocal microscopy (RCM), a noninvasive imaging technique that allows a real-time, high-resolution imaging of the skin, although no histological confirmation was provided. The aim of the present study was to compare the RCM evaluation of DP density in healthy skin with horizontal histopathological sections (HHS), a technique that provides a horizontal view of the skin.

Method: Ten adult patients were selected, and a healthy skin area was marked for RCM examination and a subsequent 5-mm punch biopsy that was processed for HHS. Two different blinded operators performed DP counting on RCM and HHS images, respectively.

Results: A total of 10 skin samples were obtained from the lower back. The mean DP density resulting from RCM was 84.27 ± 3.24/mm2, while that from HHS was 84.08 ± 2.74/mm2. Student t test showed no significant differences in DP count between the two techniques (p = 0.89).

Discussion: The strength of this study is represented by the histological evaluation which has never been previously performed, whose results align with the RCM findings and validate previous data from our group, with negligible differences. We believe that the exact identification of the DP number in normal skin may have practical implications, as several inflammatory skin conditions are characterized by DP changes such as psoriasis, lichen planus, and discoid lupus.

Introduction: Adrenergic modulation of sweating remains equivocal in females. We investigated whether α₁- and α₂-adrenergic receptors can modulate sweating during active heat stress in healthy female participants.

Methods: Thirty young adults (15 females) cycled at 50% peak oxygen uptake for 30 min at 32°C and 40% relative humidity. Sweat rates (ventilated capsule technique) on both forearms were assessed following pretreatment with terazosin (α₁-adrenergic receptor antagonist), rauwolscine (α₂ antagonist), or control (NaCl) using transdermal iontophoresis procedure. The efficacy of α₁ blockade was confirmed postexercise with phenylephrine (α₁-adrenergic agonist)-induced sweating, while α₂ antagonist efficacy was verified in a separate follow-up study assessing clonidine (α₂ agonist)-induced cutaneous vasoconstriction.

Results: Participants sweated by 0.32 ± 0.13 and 0.54 ± 0.26 mg∙cm-2∙min-1 at the end of exercise for females and males, respectively. Neither terazosin nor rauwolscine affected sweating during exercise in males (p ≥ 0.125, interaction and treatment effect) or females (p ≥ 0.277) as compared to control sites. However, the reduction in sweat rate at the terazosin-treated site was negatively correlated with sweat rate at control sites in both sexes (all p ≤ 0.050, r ≤ -0.514), while no such correlation was observed for rauwolscine. Successful α₁-blockade was confirmed by attenuated phenylephrine-induced sweating during postexercise (p ≤ 0.025). Rauwolscine effectively abolished clonidine-induced cutaneous vasoconstriction in a follow-up study, verifying successful transdermal delivery.

Conclusion: The α₁- and α₂-adrenergic receptors do not alter sweating during moderate-intensity exercise in males and females, at least among individuals with relatively low sweat production.

Introduction: In women during pregnancy and in infants during the first months after birth, skin health is challenged. However, evidence about the structural and functional changes of the skin during and after pregnancy is largely lacking.

Methods: The first prospective cohort study was conducted, following women from pregnancy through the postpartum period and their infants until 6 months of age, with skin structure and function measured at different time points. Due to the explorative character of the study, descriptive statistics were used.

Results: Over the study period, transepidermal water loss, epidermal thickness, and skin roughness in women increased. Pregnancy and postpartum period affected skin parameters such as skin roughness, epidermal thickness, and transepidermal water loss, whereas stratum corneum hydration, pH, skin stiffness, and skin elasticity were not affected in women. Infants' skin barrier function matched literature values for healthy skin, with roughness and dryness decreasing through 6 months of age. Infants' skin barrier function characteristics matched literature values for healthy skin, with skin roughness and dryness decreasing by 6 months of age.

Conclusion: Based on the findings of this observational cohort study, we found no statistically significant correlation between maternal health and skin characteristics and skin characteristics of infants except for women's skin roughness and infants' skin stiffness and skin elasticity and women's skin stiffness and skin elasticity and infants' skin elasticity. Therefore, based on our findings it may be justified to consider using skin care for maintaining barrier quality and function: (a) in pregnant women with a positive effect on skin roughness and transepidermal water loss and (b) in infants improving dry skin and skin roughness.

Introduction: The skin serves as a barrier, preventing internal moisture loss and protecting against the invasion of external harmful factors while also playing a role in immune responses. Barrier disruption is a hallmark of inflammatory skin diseases characterized by dryness and itching, notably in conditions like atopic dermatitis (AD). Recent research has focused on exploring novel compounds that can enhance skin barrier function and modulate inflammatory responses. Therefore, this study aimed to investigate the barrier-protective role and underlying mechanisms of lipimoide in an AD-like skin barrier impairment model using normal human keratinocytes and human skin equivalent models.

Method: An in vitro AD-like condition was induced in normal human epidermal keratinocytes (NHEKs) and a human skin equivalent models by treating with a stimulus cocktail containing Th2 cytokines (IL-4 and IL-13), leading to impaired keratinocyte differentiation, increased inflammation, and epidermal thickening. Functional studies on skin barrier function, anti-inflammatory effects, and the molecular mechanisms involving TRPM8 expression were conducted using quantitative real-time PCR, Western blotting, immunofluorescence analysis, immunohistochemistry, and transepithelial electrical resistance measurements to assess skin barrier integrity.

Results: Treatment with lipimoide, a novel synthetic compound, increased the gene and protein expression of TRPM8, which had been downregulated in NHEKs and skin equivalents induced by the stimulus cocktail. Additionally, lipimoide was found to restore the expression of epidermal differentiation markers, reduce inflammation, and enhance skin barrier function in AD-like skin conditions.

Conclusion: This study indicates that TRPM8 plays a crucial role in maintaining skin barrier integrity and may serve as a therapeutic target for treating dermatitis in AD. Furthermore, as a TRPM8 modulator, lipimoide promotes epidermal barrier homeostasis and function, providing a potential therapeutic strategy for managing dry and inflammatory skin conditions.