Assessment of the Vehicle for Roflumilast Cream Compared to a Ceramide-Containing Moisturizing Cream in Mild Eczema.

BACKGROUND: Inflammatory dermatologic conditions suitable for topical treatments benefit from a hydrating vehicle that improves the skin barrier without irritation. OBJECTIVE: This research was designed to assess skin barrier effects and aesthetic attributes of the vehicle for topical roflumilast cream (vehicle) vs a currently marketed ceramide-containing moisturizing cream (moisturizer). METHODS: This was a single-site, randomized, intraindividual, double-blind, controlled study conducted over 17 days. Patients (aged 18 years or older) with mild, symmetric asteatotic eczema of the lower extremities were enrolled to receive lower leg applications of the vehicle on one leg and moisturizer on the other. The primary efficacy endpoint was a change in transepidermal water loss (TEWL) from baseline to day 15. Secondary efficacy endpoints included change from baseline in TEWL at other study visits, change from baseline in hydration as assessed via corneometry, and patient- and investigator-rated assessments of the products. Safety and tolerability were also assessed. RESULTS: A total of 40 patients enrolled in the study. The primary efficacy endpoint was met for both treatments. A statistically significant difference in TEWL on day 1 favored the moisturizer, but no difference was seen between vehicle and moisturizer at any other timepoint. Both vehicle and moisturizer also met the secondary efficacy endpoint of change from baseline in hydration. LIMITATIONS: The sample size was small. CONCLUSIONS: The vehicle for roflumilast cream performed similarly to a leading, currently marketed, dermatologist-recommended, ceramide-containing moisturizer across all patient- and investigator-rated assessments of efficacy, tolerability, and aesthetic properties in patients with mild asteatotic eczema. J Drugs Dermatol. 2024;23(10):834-840. doi:10.36849/JDD.7958  .

Mask wearing impacts skin barrier function and microbiome profile in sensitive skin.

Mask-wearing behavior, common in the post-COVID-19 era, raises concerns for sensitive skin. This split-face study investigated mask-related changes in skin barrier function and microbiome composition among 30 female volunteers with sensitive skin and assessed the mitigating effects of a moisturizer containing biological lipids and probiotics. Skin physiological indicators (transepidermal water loss, erythema index, stratum corneum hydration, pH, temperature) of masked and unmasked areas were collected at baseline, after three hours of mask-wearing, post-tape stripping, and after 24 h, respectively. Microbiome samples collected from the masked areas before and after wearing a medical mask were analyzed with bioinformatics methods. Mask-wearing significantly weakened barrier function in both masked and adjacent unmasked areas, while reducing bacterial diversity. It was also associated with an increase in Cutibacterium (P = 0.110) and decreases in Streptococcus (P = 0.032) and Prevotella (P = 0.026) abundance. Moisturizer application prior to mask-wearing significantly reduced transepidermal water loss and erythema (both P < 0.001) and further improved erythema after 24 h (P = 0.048). These findings demonstrate that mask-wearing can disrupt the skin barrier and microbiome in individuals with sensitive skin and applying a moisturizer beforehand can mitigate mask-related discomforts by aiding barrier repair and reducing sensitivity.

The Effect of Polynucleotide-Hyaluronic Acid Hydrogel in the Recovery After Mechanical Skin Barrier Disruption.

BACKGROUND: The epidermal barrier acts as a defense against external agents as well as helps to maintain body homeostasis. Polynucleotides (PN), exogenous DNA fragments, promote wound repair through their stimulatory and anti-inflammatory effects. Recent findings indicate a synergistic effect of PN and hyaluronic acid (HA) combinations in regulating inflammation and promoting cell proliferation. This study aims to elucidate the effects of PN and HA on repairing the epidermal barrier following its disruption by tape stripping (TS) in a mouse model. MATERIALS AND METHODS: After disrupting the epidermal barrier using TS, a formulation containing PN (14 mg/mL) and HA (6 mg/mL) was applied. Trans-epidermal water loss (TEWL) was measured at 0, 3, 6, 24, 48, and 72 h. Mice were euthanized after the final application at 72 h, and tissue samples were analyzed for epidermal/dermal thickness, neutrophil infiltration, and filaggrin expression. RESULTS: We observed a significant reduction in TEWL in the PN+HA group compared to that in the control group (20.8 ± 0.5 vs. 43.7 ± 0.5 g/m2h at 72 h, p < 0.05), indicating an improvement in barrier function. Histological evaluation showed decreased epidermal and dermal thickening in the PN+HA group compared to that in the control group (epidermal: 29.4 ± 2.2 vs. 57.9 ± 3.5 µm; dermal: 464.8 ± 25.9 vs. 825.9 ± 44.8 µm, both p < 0.05). Additionally, neutrophil infiltration in the dermis was significantly reduced, and filaggrin protein levels were significantly higher in the PN+HA group compared to those in the control group (4.8 ± 0.4 vs. 21.1 ± 3.3 for neutrophils; 0.84 ± 0.04 vs. 0.42 ± 0.03 for filaggrin, both p < 0.05). CONCLUSION: These results suggest that PN+HA may be an effective therapeutic strategy for repairing skin barrier damage.

Novel Cosmetic Ingredient CS-AA Polyion Complex and Skin Moisturizing Effect.

PURPOSE: The study explored the enhanced skin moisturizing capabilities and moisture retention effects achieved by forming a polyion complex using sulfated glycosaminoglycan (GAG), specifically chondroitin sulfate (CS), and amino acids (AA) such as glutamine (Q) and arginine (R). The overall hydration effect of this CS-AA complex was examined. METHODS: After analyzing the CS-AA polyion complex structure using spectroscopic methods, the ex vivo moisture retention ability was assessed under dry conditions using porcine skin samples. Additionally, the efficacy of the CS-AA polyion complex in reducing transepidermal water loss (TEWL) and improving skin hydration was evaluated on human subjects using a digital evaporimeter and a corneometer, respectively. RESULTS: Validating a systematic reduction in particle size, the following order was observed: CS > CS/AA simple mixture > CS-AA complex based on dynamic light scattering (DLS) and transmission electron microscopy (TEM) analysis. Furthermore, observations revealed that the CS-AA complex exhibits negligible surface charge. Additionally, Fourier-transform infrared spectroscopy (FT-IR) analysis demonstrated a distinct peak shift in the complex, confirming the successful formation of the CS-AA complex. Subsequently, the water-holding effect through porcine skin was assessed, revealing a notable improvement in moisture retention (weight loss) for the CS-Q complex: 40.6% (1 h), 20.5% (2 h), and 18.7% (4 h) compared to glycerin. Similarly, the CS-R complex demonstrated enhancements of 50.2% (1 h), 37.5% (2 h), and 33% (4 h) compared to glycerin. Furthermore, TEWL improvement efficacy on human skin demonstrated approximately 25% improvement for both the CS-Q complex and CS-R complex, surpassing the modest 12.5% and 18% improvements witnessed with water and glycerin applications, respectively. Finally, employing a corneometer, hydration changes in the skin were monitored over 4 weeks. Although CS alone exhibited nominal alterations, the CS-Q complex and CS-R complex showed a significant increase in moisture levels after 4 weeks of application. CONCLUSION: In this study, polyion complexes were successfully formed between CS, a sulfated GAG, and AA. Comparisons with glycerin, a well-known moisturizing agent, confirmed that the CS-AA complex exhibits superior moisturizing effects in various aspects. These findings suggest that the CS-AA complex is a more effective ingredient than CS or AA alone in terms of efficacy.

Restoration of Skin Barrier Abnormalities with IL4/13 Inhibitors and Jak Inhibitors in Atopic Dermatitis: A Systematic Review.

Background and Objectives: Atopic dermatitis is a chronic inflammatory skin disorder with a significant burden on patients' quality of life. This systematic review aims to evaluate the restoration of skin barrier abnormalities with interleukin-4/interleukin-13 (IL-4/IL-13) inhibitors and Janus kinase (JAK) inhibitors in atopic dermatitis. Materials and Methods: A comprehensive review of the literature was conducted, focusing on studies that assess the use of IL-4/IL-13 inhibitors and JAK inhibitors for atopic dermatitis. We identified eligible studies by searching Medline via PubMed with a special focus on their effect on the restoration of the epidermal barrier. Included studies evaluated the transepidermal water loss (TEWL), the reduction in epidermal thickness (ET), the improvement in ceramide synthesis, and the increase in stratum corneum hydration (SCH) with IL-4/IL-13 inhibitors and JAK inhibitors. The quality of included studies was assessed using the ROBINS-I and the RoB 2.0 tool for assessing the risk of bias. Results: Ten of the included studies concern dupilumab, while two concern JAK inhibitors. Ten were observational studies and two were randomized controlled trials (RCTs). The total number of included participants was 378 concerning dupilumab and 38 concerning JAK inhibitors. Five studies did not include any comparison group, three included healthy volunteers, two were conducted versus placebo, and two compared dupilumab with other treatments. The follow-up period ranged between 29 days and 32 weeks. The results demonstrated a significant decrease in transepidermal water loss (TEWL) and an increase in SCH on eczematous lesions for patients with sustained response to dupilumab treatment and observed improvements in ET and filaggrin (FLG) staining, which further support the efficacy of JAK inhibitors in enhancing skin barrier function. Conclusions: This review underscores the efficacy of IL-4/IL-13 inhibitors in improving skin barrier function. However, the limited number of studies focusing on JAK inhibitors and the overall lack of RCTs highlight the need for further research to establish the definitive role of IL-4/IL-13 inhibitors and JAK inhibitors in the restoration of the skin barrier.

Clinical Evaluation of the Efficacy of Itch-Relief Moisturizers Containing Maltotetraose for Dry, Itchy, and Sensitive Skin.

Itching is a prominent clinical manifestation of sensitive skin; it reduces cutaneous barrier function, mainly caused by dryness. Scratching to relieve itching destroys the skin barrier, thus forming the itch-scratch cycle that results in additional disruption of skin barrier and chronic itching. Treatment involves alleviation from itching for sensitive skin. Recently, substance P (11-amino acid neuropeptide of the tachykinin family) and neurokinin 1 receptor (NK1R) have been considered to provide a key pathway to treat chronic itching. A single-center, open-label study was conducted comprising subjects with dry, itchy, and sensitive skin to evaluate the efficacy of two types of itch-relief moisturizers, mist and lotion, containing maltotetraose (MTO). In all, 35 subjects used mist containing MTO, resulting in significant improvement in itch score from 1 minute to 2 hours following single application. On the other hand, 34 subjects applied lotion containing MTO for 1 week, resulting in significant improvement in itch score, skin hydration, and clinical scores of erythema/redness and dryness; however, in both cases, improve-ment was not observed in the measurement of transepidermal water loss (TEWL). It was concluded that two types of itch-relief moisturizers containing MTO were effective for dry, itchy, and sensitive skin.

Polygalacturonic acid partially inhibits matrix metalloproteinases and dehydration in wounds.

BACKGROUND: Key wound environment parameters include pH, hydration, and the balance between tissue remodeling and deposition of new tissue. When prolonged inflammation is present, the proliferation phase of wound healing can be delayed because excessive protease production due to persistent inflammation can destroy newly formed tissue and prevent wounds from filling and reepithelializing. OBJECTIVE: To conduct an in vitro study of the ability of polygalacturonic acid (PG), a natural pectin derivative present in ripening fruit, to inhibit 3 destructive wound proteases and prevent dehydration in environments in which significant evaporation can occur. MATERIALS AND METHODS: In vitro enzyme inhibition assay kits were used to detect the ability of PG to inhibit key wound proteases matrix metalloproteinase (MMP)-2, MMP-9, and neutrophil elastase (NE). Transepidermal evaporative water loss from a polyvinyl alcohol skin substitute hydrogel was gravimetrically measured. RESULTS: PG could partially inhibit MMP-2 (>50% inhibition relative to negative controls), MMP-9 (>50% inhibition relative to negative controls), and NE (>25% inhibition relative to negative controls) and thereby potentially blunt some of the destructive effects of excess proteases where prolonged inflammation is present. In an in vitro transepidermal evaporative water loss assay, PG also helped retain moisture and inhibited dehydration (>25% reduction relative to negative controls). CONCLUSIONS: These findings suggest that PG can be a useful addition to ointments and dressings in wound care and warrants further in vivo testing.

Efficacy and Safety of Oral Administration of Wine Lees Extract (WLE)-Derived Ceramides and Glucosylceramides in Enhancing Skin Barrier Function: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND: Our search for plant-derived ceramides from sustainable sources led to the discovery of ceramides and glucosylceramides in wine lees. OBJECTIVE: This study evaluated the efficacy and safety of wine lees extract (WLE)-derived ceramides and glucosylceramides in enhancing skin barrier function. METHODS: A randomized, double-blind, placebo-controlled study was conducted with 30 healthy Japanese subjects aged 20-64. Subjects were allocated to receive either the WLE-derived ceramides and glucosylceramides (test group) or placebo for 12 weeks. The primary outcome was transepidermal water loss (TEWL), and secondary outcomes included skin hydration, visual analog scale (VAS) of itching sensation, and the Japanese Skindex-29. RESULTS: One participant withdrew for personal reasons, resulting in 29 subjects for data analysis (placebo n = 15; test n = 14). The test group showed a tendency of lower TEWL compared to the placebo after 8 weeks (p = 0.07). Furthermore, after 12 weeks of administration, the test group had significantly lower TEWL than the placebo (p = 0.04). On the other hand, no significant differences were observed in the secondary outcome parameters. No adverse events related to the supplements were reported. CONCLUSIONS: Oral supplementation of WLE-derived ceramides and glucosylceramides is a prominent and safe approach to enhancing skin barrier function and health. TRIAL REGISTRATION: (UMIN000050422).

Effects of lead on avian thermoregulation in the heat: An experimental test with pied crows (Corvus albus).

Many of the negative physiological effects of lead involve the hypothalamus, but the possibility that thermoregulation is affected has received little attention. We tested the hypothesis that lead exposure reduces avian thermoregulatory performance under hot conditions in pied crows (Corvus albus) experimentally exposed to lead in their diet. Crows in our high lead treatment (blood [Pb] = 87.3 ± 44.7 µg dL-1) showed significantly higher air temperature (Tair) inflections for evaporative water loss (EWL) and resting metabolic rate (RMR) compared to control (6.4 ± 1.8 µg dL-1) or intermediate (53.9 ± 23.7 µg dL-1) lead groups, which did not differ. EWL, RMR and body temperature (Tb) all increased more rapidly at Tair > Tb in the high lead treatment. In contrast, neither maximum Tair tolerated by the crows nor maximum Tb varied with treatment. Our data reveal that water and energy balance during hot weather is affected by lead exposure.

Effectiveness of topical hyaluronic acid of different molecular weights in xerosis cutis treatment in elderly: a double-blind, randomized controlled trial.

Dry skin is a common dermatological condition that frequently affects the elderly. A contributing cause to dry skin is a reduced concentration of hyaluronic acid (HA) in both the epidermis and dermis. The effectiveness of moisturizer containing HA as a therapy for dry skin is impacted by its specific molecular weight. Low molecular weight HA (LMWHA) is believed to be more effective in replenishing skin hydration in aging skin compared to High Molecular Weight HA (HMWHA) due to its ability to penetrate the stratum corneum. However, there is a lack of clinical research supporting this claim. A double-blind, randomized controlled trial was conducted on 36 residents of a nursing home in Jakarta. The participants, aged between 60 and 80 years, had been diagnosed with dry skin. Each test subject was administered three distinct, randomized moisturizing lotions (LMWHA, HMWHA, or vehicle), to be topically applied to three separate sites on the leg. Skin capacitance (SCap), transepidermal water loss (TEWL), and specified symptom sum score (SRRC) were measured at weeks 0, 2, and 4. After four weeks of therapy, area that was treated with LMWHA showed greater SCap values compared to the area treated with HMWHA (56.37 AU vs. 52.37 AU, p = 0.004) and vehicle (56.37 AU vs. 49.01 AU, p < 0.001). All groups did not show any significant differences in TEWL and SRRC scores. No side effects were found in all groups. The application of a moisturizer containing LMWHA to the dry skin of elderly resulted in significant improvements in skin hydration compared to moisturizers containing HMWHA and vehicle. Furthermore, these moisturizers demonstrated similar safety in treating dry skin in the elderly. ClinicalTrials.gov Identifier NCT06178367, https://clinicaltrials.gov/study/NCT06178367 .

Friction Dynamics of Human Skin Treated using Polymer Aqueous Solutions.

Herein, we evaluated friction dynamics of human skin treated with polyacrylic acid aqueous solutions or gel creams using a sinusoidal motion friction evaluation system to demonstrate the effect of treatment with polymer aqueous solutions on human skin. A polymer aqueous solution or gel cream was applied to the inner forearms of 10 subjects to evaluate temporal changes in friction force under sinusoidal motion. Water content, skin viscoelasticity, and transepidermal water loss were also simultaneously measured to determine the effects on skin conditions. When human skin was treated with the polymer aqueous solution, the friction coefficient immediately after treatment was 0.69-0.99 and the delay time δ, a normalized parameter of the time difference in the delayed response of friction to the movement of the contact probe divided by the friction time T 0 for one round trip, was 0.171-0.179, which was greater than that of untreated skin. This increase was caused by the swelling and softening of the stratum corneum caused by the penetration of water in the polymer aqueous solution, which increased true contact area between the skin and contact probe. A significant difference was observed in the friction coefficient of the skin immediately after treatment with different polymer aqueous solutions. Among polymers (P1-P4), P4, which has a low-salt resistance and low yield stress, had the lowest friction coefficient because of collapsing of the polymer network structures by shearing and reduced viscosity owing to salts on human skin. The skin treated with a gel cream also exhibited a greater friction coefficient than the untreated skin immediately after treatment and 90 min later. This phenomenon can be caused by the occlusive effect of the oil in the gel cream.

Fabrication and efficacy assessment of combination of brimonidine and ivermectin for treatment of papulopustular rosacea.

BACKGROUND & AIM: Rosacea is a chronic inflammatory, multifactorial disease for which combination therapy could be an effective treatment. In this study, we evaluate the effect of the combination therapy of brimonidine 0.33% and ivermectin 1% as a single cream for the treatment of papulopustular rosacea. METHOD: A stable and appropriate formulation was prepared by adding the aqueous phase to the lipid phase while being stirred. The stability and physicochemical properties of the formulation were evaluated under accelerated conditions. Twelve patients (36-60 years) with mild to moderate papulopustular rosacea and a Demodex count of five or more were treated with the combination of brimonidine 0.33% and ivermectin 1% cream. Clinician's Erythema Assessment (CEA), Patients Self-Assessment (PSA), skin erythema (ΔE) and lightness (ΔL), and skin biophysical parameters including transepidermal water loss (TEWL), skin hydration, pH, and sebum content, as well as erythema and melanin index and ultrasound parameters, were measured before treatment and 4 and 8 weeks after. Adverse drug reactions were also recorded. RESULTS: CEA and PSA decreased significantly from 3 to 2 after 8 weeks, respectively (p-value = 0.014 for CEA and 0.010 for PSA). ΔE and ΔL, as well as skin erythema index and TEWL improved after 8 weeks of treatment (p < 0.05). Two patients withdrew from the study in the first week because of local adverse effects; one developed flushing following treatment and left the investigation after 4 weeks and another patient withdrew from the study after 4 weeks due to deciding to become pregnant. CONCLUSION: Eight-week treatment with the combination of brimonidine 0.33% and ivermectin 1% was shown to be effective for improvement of erythema and inflammatory lesions in mild to moderate papulopustular rosacea.

Going Beyond Ceramides in Moisturizers: The Role of Natural Moisturizing Factors.

Xerosis is experienced by almost everyone at some time in their lives and the foundation of management of dry skin (both consumer- and healthcare professional--directed) rests on the use of moisturizers. Given the wide range of available moisturizers, counseling patients about selecting the optimum moisturizer for their individual situation relies on knowledge of ingredients and formulations. Traditionally, the main focus for many moisturizers centered on the core functional and structural role of ceramides within the epidermal barrier.  However, while a key aspect of transepidermal water loss and other skin barrier functions, components other than ceramides are equally essential in increasing moisturization. The skin's natural moisturizing factors (NMFs) are a complex mixture of water-attracting compounds such as amino acids, urea, lactate, pyrrolidone carboxylic acid (PCA), and electrolytes which play a fundamental role in preserving physiologic function by regulating the water content of the stratum corneum. By facilitating water retention, NMFs contribute significantly to the suppleness, elasticity, normal desquamation, and overall integrity of the skin barrier. Incorporation of NMFs into moisturizers addresses critical deficiencies in the skin's moisture balance that exist in xerotic and atopic skin, and in many skin disorders, mitigating signs and symptoms associated with xerosis and promoting optimal skin health. The biochemical composition of NMFs and the intricate interplay with epidermal homeostasis translate to a central role in moisturizers used for prophylactic and therapeutic management of various dry skin conditions, beyond ceramides alone. J Drugs Dermatol. 2024;23(6):466-471.     doi:10.36849/JDD.8358.

Oral tranexamic acid treats papulopustular rosacea by improving the skin barrier.

BACKGROUND: Papulopustular rosacea (PPR) is a chronic inflammatory disease with a significant impact on facial aesthetics. An impaired skin barrier is an important factor in the development and exacerbation of PPR. Tranexamic acid (TXA) has immune regulatory and anti-inflammatory effects, inhibits angiogenesis and endothelial hyperplasia, and promotes skin barrier repair. AIMS: We investigated the efficacy and safety of oral TXA for PPR treatment. PATIENTS/METHODS: In total, 70 patients were randomly assigned to receive traditional therapy plus oral TXA or traditional therapy alone for 8 weeks, with a 4-week follow-up period. The subjective improvement in rosacea was assessed using the clinical erythema assessment (CEA), investigator's global assessment (IGA), patient self-assessment (PSA) score, rosacea-specific quality of life (RQoL) score, and global aesthetic improvement score (GAIS). An objective improvement in rosacea was assessed using skin hydration, trans-epidermal water loss (TEWL), clinical photography, and an eight spectrum facial imager. RESULTS: CEA/IGA/PSA, dryness, and RQoL scores were significantly lower and GAIS was higher in the TXA group than in the traditional therapy group. Furthermore, oral TXA significantly improved skin barrier function, increased skin hydration, and decreased TEWL, with no significant side effects. Notably, we observed better outcomes and a greater improvement in skin barrier function with TXA treatment in patients with dry-type rosacea than in patients with oily skin. CONCLUSIONS: The addition of oral TXA to traditional therapy can lead to rapid and effective improvements in PPR, which may be attributed to improvements in skin barrier function.

The impact of irritant challenge on the skin barrier and myeloid-resident immune cells in women who are postmenopausal is modulated by hormone replacement therapy.

BACKGROUND: Sex hormone changes during menopausal transition contribute to declining skin health. However, how menopause and its treatment by hormone replacement therapy (HRT) impact the skin barrier and immune system is unclear. OBJECTIVES: To examine how menopause and HRT affect the skin barrier and immune cell composition in postmenopausal women following irritant challenge. METHODS: Two cohorts of postmenopausal women were recruited to the study. The first cohort consisted of 10 untreated women [HRT-; mean (SEM) age 56.5 (1.6) years (range 48-63)] and the second was composed of 8 women receiving HRT [HRT+; mean (SEM) age 54.0 (2.1) years (range 48-63)]. Skin irritation was induced by applying topical sodium lauryl sulfate (SLS) 1.25% to occluded buttock skin for 48 h. Clinical assessment was conducted after 24 h, followed by biopsy of both SLS-challenged and unchallenged skin for analysis of skin barrier proteins and immune cell distribution using immunofluorescence. RESULTS: Clinically, there were no significant differences in skin irritant responses between those taking or not taking HRT (including increased skin redness and blood flow). In response to SLS challenge a significant increase in transepidermal water loss (P < 0.05), filaggrin deposition and cytokeratin 10 (K10)+ cell layers (P < 0.01) was observed in individuals receiving HRT compared with the HRT- group. Following SLS challenge in individuals taking HRT, a significant (P < 0.01) reduction in CD207+ cells in the epidermis was observed, accompanied by an increase of CD207+ cells in the dermis, indicative of migrating Langerhans cells (LCs). Significantly fewer migrating LCs were found in those who were not receiving HRT (P < 0.01). Furthermore, the numbers of dermal dendritic cells (DCs), macrophages, and CD11c+CD206- and CD68+CD206- subsets were found to be significantly (P < 0.05) higher in those taking HRT following SLS challenge. CONCLUSIONS: Individuals receiving HRT displayed enhanced skin barrier response to SLS challenge with thicker filaggrin and increased K10+ epidermal cell layers. Following challenge, HRT users exhibited elevated LC, inflammatory DC and macrophage counts in the dermis. These may render skin both more prone to inflammation and more capable of resolving it, while also promoting skin repair.

Changes to a person's sex hormones during the menopause can affect the skin. The effects of the menopause on the immune system and the skin are still unclear. The effects of a treatment called 'hormone replacement therapy' ('HRT') are also still unclear. We investigated the effects of HRT on immune cells and skin barrier function in women who had been through the menopause. To do this, we compared the skin of two groups of women: those who were taking HRT and those who were not. Looking at skin redness and blood flow, we found that the two groups of women had a similar response to their skin being irritated by a chemical called 'SLS'. Yet, the women taking HRT had increased water loss from their skin after SLS was applied. We also found that after having SLS applied, women on HRT had a thicker layer of cells in the top section of their skin that produced more of a protein that helps protect the skin. Women taking HRT also had more inflammatory cells in the deeper layers of their skin after SLS was applied. Overall, our findings suggest that HRT may improve the skin's immune response to irritating substances. HRT could have an effect on the skin's ability to repair itself and on general skin health.

Open-label topical application of tetrahexyldecyl ascorbate and acetyl zingerone containing serum improves the appearance of photoaging and uneven pigmentation.

BACKGROUND: Skin photoaging and uneven pigmentation are common dermatological concerns. Tetrahexyldecyl ascorbate (THDA) and acetyl zingerone (AZ) are potent antioxidants that have been shown to have anti-photoaging and anti-pigmentation effects. THDA is a more stable and penetrable form of vitamin C. AZ is an antioxidant derived from ginger which has clinical evidence for improving photoaging. However, no studies have assessed how they may synergistically act on the skin. AIMS: This study aims to assess whether a serum containing both THDA and AZ can improve photoaging and the appearance of uneven facial pigmentation. PATIENTS/METHODS: This open-label study was conducted on 35 healthy individuals aged 21-55. All subjects were instructed to use three to five drops of the topical serum (Power-C Serum, Image Skincare, Lantana, FL) daily for 12 weeks. Videomicroscopy and high-resolution photography and various skin biophysical measurements were taken at baseline, 1, 4, and 12 weeks. Outcomes included skin tone and pigmentation, transepidermal water loss (TEWL), skin smoothness, firmness, and elasticity. RESULTS: Compared to baseline, the results at 12 weeks revealed significant decreases in skin pigmentation (p < 0.0001), decreased fine lines and wrinkles (p < 0.0001), and increased smoothness (p < 0.0001), firmness (p < 0.0001), and elasticity (p < 0.0001). Additionally, transepidermal water loss was significantly decreased at 4 weeks compared to baseline (p = 0.01), indicating an increased epidermal barrier integrity. CONCLUSIONS: Overall, these findings provide evidence for the combined use of THDA and AZ to address skin photoaging and dyspigmentation changes.

Dissolvable microneedles in the skin: Determination the impact of barrier disruption and dry skin on dissolution.

Dissolvable microneedles (DMNs), fabricated from biocompatible materials that dissolve in both water and skin have gained popularity in dermatology. However, limited research exists on their application in compromised skin conditions. This study compares the hyaluronic acid-based DMNs penetration, formation of microchannels, dissolution, and diffusion kinetics in intact, barrier-disrupted (tape stripped), and dry (acetone-treated) porcine ear skin ex vivo. After DMNs application, comprehensive investigations including dermoscopy, stereomicroscope, skin hydration, transepidermal water loss (TEWL), optical coherence tomography (OCT), reflectance confocal laser scanning microscopy (RCLSM), confocal Raman micro-spectroscopy (CRM), two-photon tomography combined with fluorescence lifetime imaging (TPT-FLIM), histology, and scanning electron microscopy (SEM) were conducted. The 400 µm long DMNs successfully penetrated the skin to depths of ≈200 µm for dry skin and ≈200-290 µm for barrier-disrupted skin. Although DMNs fully inserted into all skin conditions, their dissolution rates were high in barrier-disrupted and low in dry skin, as observed through stereomicroscopy and TPT-FLIM. The dissolved polymer exhibited a more significant expansion in barrier-disrupted skin compared to intact skin, with the smallest increase observed in dry skin. Elevated TEWL and reduced skin hydration levels were evident in barrier-disrupted and dry skins compared to intact skin. OCT and RCLSM revealed noticeable skin indentation and pronounced microchannel areas, particularly in barrier-disrupted and dry skin. Additional confirmation of DMN effects on the skin and substance dissolution was obtained through histology, SEM, and CRM techniques. This study highlights the impact of skin condition on DMN effectiveness, emphasizing the importance of considering dissolvability and dissolution rates of needle materials, primarily composed of hyaluronic acid, for optimizing DMN-based drug delivery.

Blockade of interleukin-13 signalling improves skin barrier function and biology in patients with moderate-to-severe atopic dermatitis.

BACKGROUND: Interleukin (IL)-13 is a key driver of inflammation and barrier dysfunction in atopic dermatitis (AD). While there is robust evidence that tralokinumab - a monoclonal antibody that neutralizes IL-13 - reduces inflammation and clinical disease activity, less is known about its effects on barrier function. OBJECTIVES: To characterize the effects of tralokinumab treatment on skin barrier function. METHODS: Transepidermal water loss (TEWL), stratum corneum hydration (SCH), natural moisturizing factor content, histopathological characteristics, biomarker expression and microbiome composition were evaluated in lesional, nonlesional and sodium lauryl sulfate-irritated skin of 16 patients with AD over the course of 16 weeks of tralokinumab treatment. RESULTS: All clinical severity scores decreased significantly over time. At week 16, mean TEWL in target lesions decreased by 33% (P = 0.01) and SCH increased by 58% (P = 0.004), along with a histological reduction in spongiosis (P = 0.003), keratin 16 expression and epidermal thickness (P = 0.001). In parallel, there was a significant decrease in several barrier dysfunction-associated and proinflammatory proteins such as fibronectin (P = 0.006), CCL17/TARC (P = 0.03) and IL-8 (P = 0.01), with significant changes seen as early as week 8. Total bacterial load and Staphylococcus aureus abundance were significantly reduced from week 2. CONCLUSIONS: Tralokinumab treatment improved skin physiology, epidermal pathology and dysbiosis, further highlighting the pleiotropic role of IL-13 in AD pathogenesis.

Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized by a marked skin barrier impairment. The skin barrier deficiency is characterized by an imbalance of organisms naturally found on the skin, including a reduction in the diversity of organisms and an increased amount of bacteria called Staphylococcus aureus. Further, there are reduced structural proteins, problems with 'tight junctions' (which maintain skin integrity) and abnormalities in the make-up/organization of skin lipids. As a result, the skin cannot keep itself hydrated or moisturized, and there is an increased likelihood of 'irritant contact dermatitis' (for example, rashes, dry skin and itching). 'Interleukin (IL)-13' is a signalling protein found in the immune system that is increased in AD and causes inflammation. Tralokinumab is a drug that neutralizes IL-13 and reduces inflammation and the severity of AD; however, less is known about its effect on the skin barrier. This study aimed to investigate the effects of tralokinumab on skin barrier function by looking at levels of water loss, hydration, natural moisturizing factor content, histopathological characteristics (how it looks under a microscope), the expression of biomarkers (indicators of a particular condition) and composition of the microbiome (organisms living together) in the upper skin layer of 16 people with AD who were treated with tralokinumab for 16 weeks. We found that blocking IL-13 leads to a better skin barrier with less water loss and better hydration, as well as the normalization of skin bacteria. The skin was also less irritable, and its microscopic appearance was similar to normal skin after 16 weeks of treatment. Finally, the drug appeared to be effective and safe. Overall, our findings suggest that by neutralizing IL-13, tralokinumab could help to restore the skin barrier function of people with AD.

Frequent oil baths and skin barrier during infancy in the PreventADALL study.

BACKGROUND: In the general population randomized controlled trial PreventADALL, frequent emollient bath additives from 2 weeks of age did not prevent atopic dermatitis, while the effect on skin barrier function throughout infancy is not established. OBJECTIVES: The primary aim of this exploratory substudy was to assess the effect of mineral-based oil baths on transepidermal water loss (TEWL) and dry skin through infancy, and secondarily to explore if filaggrin (FLG) mutations modified the effect. METHODS: Overall, 2153 infants were included and randomized to either the 'Skin intervention' (SI) group (n = 995) (oil bath 4 times weekly from 2 weeks through 8 months) or 'No skin intervention' (NSI) group (n = 1158), with TEWL measurements at 3, 6 and/or 12 months of age. Information on FLG mutation status was available for 1683 of these infants. Effects of the skin intervention on TEWL and dry skin through infancy were assessed by mixed-effects regression modelling. Background characteristics and protocol adherence were collected from electronic questionnaires, birth records and weekly diaries. RESULTS: The TEWL (95% confidence interval) was on average 0.42 g m-2 h-1 (0.13-0.70, P = 0.004) higher in the SI group compared with the NSI group through the first year of life, with significantly higher levels at 3 months [8.6 (8.3-9.0) vs. 7.6 (7.3-7.9)], but similar at 6 and 12 months. Dry skin was observed significantly more often in the NSI group compared with the SI group at 3 months (59% vs. 51%) and at 6 months of age (63% vs. 53%), while at 12 months of age, the difference was no longer significant. At 3 months, the TEWL of FLG mutation carriers was similar to the TEWL in the SI group. No interaction between SI and FLG mutation was found in the first year of life. CONCLUSIONS: Infants given frequent oil baths from 2 weeks of age had reduced skin barrier function through infancy compared with controls, largely attributed to higher TEWL at 3 months of age, while the skin at 3 and 6 months appeared less dry in infants subjected to the skin intervention.

Atopic dermatitis (AD) affects approximately 20% of children in industrialized countries. AD causes dry, itchy skin and can increase the chance of infections. This study was a substudy of the large Scandinavian PreventADALL trial, including 2394 infants, recruited from the general population between 2014 and 2016. Children in this trial were allocated randomly to receive either a skin intervention, food intervention, combined intervention, or no intervention. Children were examined at 3, 6 and 12 months of age. The examinations involved an investigation of the skin, to evaluate dry skin and skin barrier function by transepidermal water loss (TEWL) in the outer layers of the skin (higher TEWL suggests decreased skin barrier function). The skin intervention consisted of oil baths at least 4 times per week from 2 weeks of age through 8 months of age, and have previously not been shown to prevent AD by 1 and 3 years of age. We aimed to investigate whether frequent oil baths had any effect on TEWL and dry skin. We found that the skin intervention increased TEWL in the first year of life, especially at 3 months of age. Dry skin was less common in the skin intervention groups compared with the groups with no skin intervention. Infants with mutations in the gene coding for a skin barrier protein, called filaggrin, were associated with increased TEWL; however, in the skin intervention group, TEWL was similar among the infants with or without filaggrin mutations. Our findings suggest that oil baths several times per week from early infancy transiently decreases skin barrier function.

Lipid-based eye drop formulations for the management of evaporative dry eyes.

Dry eye disease is a progressive prevalent ocular surface disorder that arises from various factors and is characterized by insufficient quality and/or quantity of tears. The underlying pathophysiology is intricate and can progress to chronic, difficult-to-treat conditions. Multiple strategies and therapeutic approaches are utilized in its management that target one or more etiopathological components of dry eyes, which may include aqueous tear deficiency or evaporative dry eyes. The primary focus of this paper is on treatment alternatives that utilize lipids for the treatment of evaporative dry eyes. This may arise from either abnormal lipid production or inadequate lipid spreading caused by meibomian gland dysfunction. The hypothesis behind the development of these lipid-containing eye drops is that if they can imitate the lipid layer, they may be able to help in the management of the signs and symptoms of evaporative dry eyes. The lipids used in commercial formulations for dry eyes are mineral oil, castor oil, phospholipids, omega-3 fatty acid, and medium-chain triglycerides. The literature suggests the potential of lipid-containing eye drops to alleviate some of the signs and symptoms and enhance the quality of life for individuals suffering from evaporative dry eyes.