Skin Pharmacology and Physiology最新文献

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.

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.

Introduction: Turpentine derivatives and eucalyptus oil are herbal substances traditionally used to treat various skin infections. Limited non-clinical data suggest they exert an immunological activity, but only scant information exists on their antibiotic effects. This in vitro study has been carried out to investigate the antibacterial and antifungal activity of a marketed skin ointment; its active pharmaceutical ingredients larch turpentine, eucalyptus oil, and turpentine oil; and their mixture, against bacteria and yeasts commonly present on the skin and causing skin infections.

Methods: The antibiotic activity was tested using the drop dilution assay on the Gram-positive bacteria Staphylococcus aureus (wild type), a methicillin-resistant S. aureus strain, S. epidermidis, S. haemolyticus, Streptococcus pyogenes, the Gram-negative Pseudomonas aeruginosa, and the yeasts Candida albicans and C. tropicalis.

Results: The ointment exerts a strong inhibitory effect on all Gram-positive bacteria at a concentration of 5 g/100 mL in the Müller-Hinton medium. It also has inhibiting effect on both Candida species but does not inhibit P. aeruginosa growth. As for the single active pharmaceutical ingredients, larch turpentine was the most active substance. The mixture of the three ingredients, in the concentrations used in the ointment, had a higher antibiotic effect than any of the individual ingredients studied, suggesting at least an additive activity.

Conclusions: Our study has shown that the herbal ingredients and their combination exert antimicrobial activities, especially against Gram-positive bacteria, that justify their use in the treatment of skin infections.

Introduction: The in vitro Permeation Test (IVPT) is considered to be an important tool for assessing the topical pharmacokinetics of dermatologic formulations. An IVPT study evaluating products that contain the skin bleaching agent, hydroquinone (HQ), as the active ingredient, is presented in support of the value of IVPT in comparing the relative bioavailability of HQ products from different commercial products.

Methods: Ten former OTC and Rx products were evaluated for in vitro bioavailability using human ex vivo skin in Franz diffusion cells. In addition, to assess the correlation between in vitro and in vivo absorption, the suction blister technique was used to determine HQ concentration in interstitial fluid from two products differing in HQ bioavailability.

Results: Significant differences in HQ absorption between products were found. Total absorption varied from 27 to 279 μg/cm2/48 h, and neither total absorption nor the rates of absorption were found to correlate with labeled drug concentration. In vivo suction blister data on the two products were in accordance with the IVPT results.

Discussion: Overall, this study demonstrates the sensitivity and value of the IVPT method for detecting differences in the pharmacokinetics of topical formulations containing a single therapeutic agent but which differ in formulation design.

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.

Introduction: Hypertrophic scars are common fibrotic disorders marked by fibroblast overgrowth and excessive extracellular matrix deposition, necessitating further research into their formation mechanisms to improve treatment outcomes. The study investigated the clinical significance and potential mechanisms of long noncoding RNA (lncRNA) HCP5 in the development of hypertrophic scars in human fibroblasts.

Methods: The study involved 63 patients to evaluate HCP5 expression through quantitative real-time PCR. Cellular behaviors of human hypertrophic scar myofibroblasts (HSFs) were measured using CCK-8, Transwell, and flow cytometry assays. Targeting interactions between lncRNA HCP5 and miR-27b-3p were verified using a dual-luciferase reporter assay.

Results: LncRNA HCP5 was significantly upregulated in hypertrophic scar tissue. More intriguingly, the silencing of lncRNA HCP5 led to a reduction in HSFs viability and migration, while simultaneously promoting apoptosis. Furthermore, miR-27b-3p was found to be downregulated and exhibited a negative correlation with lncRNA HCP5, both factors played crucial roles in regulating cellular behavior. In addition, the inhibition of miR-27b-3p may play a role in mitigating the effects induced by silenced lncRNA HCP5 on hypertrophic scars.

Conclusion: LncRNA HCP5 influenced the biological behavior of human hypertrophic scars by targeting miR-27b-3p.

Introduction: Diesel particulate matter (DPM) emitted from diesel engines is a major source of air pollutants. DPM is composed of elemental carbon, which adsorbs organic compounds including toxic polycyclic aromatic hydrocarbons (PAHs). The skin, as well as airways, is directly exposed to DPM, and association of atopic dermatitis, psoriasis flares, and premature skin aging with air pollutant levels has been documented. In skin, the permeation of DPM and DPM-adsorbed compounds is primarily blocked by the epidermal permeability barrier deployed in the stratum corneum. Depending upon the integrity of this barrier, certain amounts of DPM and DPM-adsorbed compounds can permeate into the skin. However, this permeation into human skin has not been completely elucidated.

Methods: We assessed the permeation of PAHs (adsorbed to DPM) into skin using ex vivo normal (barrier-competent) organ-cultured human skin after application of DPM. Two major PAHs, 2-methylnaphthalene and triphenylene, and a carcinogenic PAH, benzo(a)pyrene, all found in DPM, were measured in the epidermis and dermis using liquid chromatography electrospray ionization tandem mass spectrometry. In addition, we investigated whether a topical formulation can attenuate the permeation of DPM into skin.

Results: 2-Methylnaphthalene, triphenylene, and benzo(a)pyrene were recovered from the epidermis. Although these PAHs were also detected in the dermis after DPM application, these PAH levels were significantly lower than those found in the epidermis. We also demonstrated that a topical formulation that has the ability to form more uniform membrane structures can significantly suppress the permeation of PAHs adsorbed to DPM into the skin.

Conclusion: Toxic compounds adsorbed by DPM can permeate even barrier-competent skin. Hence, barrier-compromised skin, such as in atopic dermatitis, psoriasis, and xerosis, is even more vulnerable to air pollutants. A properly formulated topical mixture that forms certain membrane structures on the skin surface can effectively prevent permeation of exogenous substances, including DPM, into skin.