Skin Pharmacology and Physiology最新文献

Eczematous cheilitis is a common issue in atopic dermatitis patients, and restoring the lip barrier function is crucial for effective management. Wet wrap dressing is frequently used as an adjuvant method to treat atopic dermatitis lesions, and a similar strategy can be applied to the treatment of atopic cheilitis. This study aimed to evaluate the short-term effects of saline gauze wet dressing on lip barrier function and to compare the clinical efficacy of gauze wet dressing as an adjuvant treatment for eczematous cheilitis. The study involved patients with eczematous cheilitis and healthy volunteers, assessing barrier function through transepidermal water loss, stratum corneum hydration, pH, and erythema values. Short-term changes were measured at 15, 30, and 60 minutes post-application, and a case-control design was used to compare the 7-day efficacy of gauze wet dressing as an adjuvant therapy to topical glucocorticoid and petroleum jelly. Results indicated that patients exhibited decreased lip barrier function, which improved significantly with gauze wet dressing, enhancing hydration and normalizing pH levels within 30 minutes. The adjuvant treatment also showed more significant clinical improvement at 7 days compared to the control group, with notable restoration of barrier function and improvement in fissure phenotype. Furthermore, the study demonstrated that the application of gauze wet dressing not only increased stratum corneum hydration and normalized pH levels but also significantly improved the clinical condition of eczematous cheilitis over the 7-day treatment period. This suggests that gauze wet dressing, as an adjunct to standard therapy, provides a convenient and cost-effective method for enhancing lip barrier function and managing eczematous cheilitis, leading to better therapeutic outcomes and patient satisfaction.

Introduction Skin senescence leads to decreased lipid and water levels, inducing xerosis with compromised barrier function. Xerosis affects ≈56% of the aging population, usually characterized by skin scaling, itching, and cracking predominating on the lower legs, causing discomfort, limited mobility and increased risk of eczema/infections. With hydrating and barrier strengthening properties, urea-based topical moisturizers are commonly used to manage skin dryness. This observational, open label, single group study, conducted in 59 participants (60 75 years), evaluated the effectiveness, tolerability and patient benefits of a 10% urea based emollient ("U10%") in the management of moderate to severe senile xerosis of the lower legs. Methods Subjects applied U10% twice daily over 4 weeks. Clinical evaluations by physicians were conducted at Baseline and Day 28 to measure changes in hydration levels, barrier function, and skin texture. Patient-reported outcomes on treatment benefits and quality of life were recorded on Day 7 and Day 28. Results After 4 weeks of treatment, meaningful improvements were observed in the global clinical assessment scores of xerosis, overall dry skin, skin roughness and dryness, total xerosis severity of the lower legs, xerosis severity for erythema, lichenification, desquamation and body surface. Corneometry measurements showed decreased trans-epidermal water loss, in line with improvements in the skin barrier function. Patient-reported outcomes showed marked improvements indicating enhancement in the overall patient perception of benefit and in the patients' quality of life resulting from treatment. Conclusion This study has provided strong evidence for the potential use of U10% emollient as a highly effective solution tailored to meet unique needs of age-related xerosis and pruritus.

Introduction: Physical exercise influences the function of multiple organs, including the skin. Previous studies demonstrated an increase in transepidermal water loss rates (TEWL) after exercise. However, TEWL measured shortly after exercise may not truly reflect the epidermal permeability barrier function. And the limited sample size may also affect the generalizability of the findings. Therefore, we assessed the influence of physical exercise on epidermal biophysical properties in a larger cohort prior to exercise.

Participants and methods: A total of 327 university students without inflammatory skin disorders or other diseases which may affect epidermal function were enrolled in this study. Epidermal biophysical properties, including TEWL, stratum corneum hydration levels and skin surface pH on the volar site of the forearm and shin were measured with a multifunctional skin physiology monitor. The correlation between epidermal biophysical properties and duration of daily exercise were determined.

Results: This cohort included 168 females and 159 males with a mean age of 18.91 ± 0.04 years. On the forearm, TEWL were lower in females than in males, while on the shin, both stratum corneum hydration levels and skin surface pH were significantly higher in females than in males. No significant differences in other parameters were observed between males and females. Overall, there were no significant differences in epidermal biophysical properties among individuals with various daily exercise duration over the past month although there was a trend of higher stratum corneum hydration levels among individuals with longer duration of daily exercise. However, TEWL on the shin of females positively correlated with the daily exercise duration.

Conclusions: There are slight but significant differences in some epidermal biophysical properties between male and female university students. Overall, exercise does not dramatically affect TEWL, stratum corneum hydration levels and skin surface pH on both the shin and forearm except on the shin of females where shows a positive correlation between the daily exercise duration and TEWL.

Introduction: Since skin tissues feature highly inter- and intraindividual variable scattering properties, it is of interest for fluorescence spectroscopy applied to skin cancer diagnostic assistance to be combined with a device able to measure scattering properties of skin tissues in vivo and further correct fluorescence spectra. This study aimed to explore the interest of combining two devices previously used in vivo during clinical trials: line-field confocal optical coherence tomography (LC-OCT) for scattering property estimation and fluorescence spectroscopy for measuring the modification of endogenous fluorescence induced by carcinogenesis.

Methods: This study was performed on liquid phantoms and on commercially available in vitro-grown 3D human skin models. Bulk scattering properties of liquid fluorescent phantoms were estimated separately at 800 nm as a function of intralipid concentration from LC-OCT images using a model based on the modified Beer-Lambert law. These results were then compared with values obtained with double-integrating spheres and collimated transmittance measurements followed by inverse adding-doubling estimation of bulk scattering properties. Changes in the amplitude of the chlorin-e6 fluorescence peak were measured as a function of IL concentration using fluorescence spectroscopy. The results obtained on phantoms were then validated with the in vitro-grown skin model.

Results: Measurements performed on liquid phantoms showed that LC-OCT overestimates scattering coefficient and anisotropy factor by approximately 20-30% compared to values measured by a method (useable only ex vivo) considered here as the gold standard: double-integrating spheres-based optical bench. Fluorescence spectroscopy was employed to measure changes in chlorin-e6 fluorescence-measured intensity relative to varying intralipid concentration. Optical characterization of human skin models confirmed their similarity with in vivo human skin in terms of morphology and of autofluorescence signals. LC-OCT was used to detect dermal scattering coefficient increase induced by impregnating the artificial skin with a PEG-400/DMSO solution that usually acts as an optical clearing agent. However, the observed effect was opposite to the typically expected decrease in the scattering coefficient, which was likely attributable to specific morphological features of the artificial skin that hindered the clearing process, resulting in only hyperosmotic effect. Spectral measurements supported these findings.

Conclusion: These findings underscore the interest of combining both optical methods, LC-OCT imaging and autofluorescence spectroscopy, to assess pathology-related fluorophore and scattering alterations in vivo.

The human epidermis is the interface between the　human body and the environment. It is mainly comprised of keratinocytes. Since the beginning of this century, functional expression of a series of receptors for various environmental factors has been reported. Moreover, neurotransmitters and hormones originally found in the central nervous system are generated and released from keratinocytes. Thus, the pathophysiology of the epidermis is important not only for skin health but also for whole-body conditions. In outer space, humans must confront environmental factors different from those on Earth, such as electromagnetic fields, drastic changes in atmospheric pressure or humidity, and microgravity. In this review, the author discusses the potential effects of these factors on epidermal homeostasis and whole-body conditions.

Introduction: Stimulated skin wrinkling (SSW) reflects the integrity of the autonomic nervous system, eccrine sweat glands, and microcirculation. Specific stimuli, as water immersion or mechanical pressure usually elicit it. This study explored the influence of some physical, chemical, sympathetic stimuli, and circadian cycle on SSW.

Methods: Time required to achieve grade III finger wrinkling was assessed in 24 healthy adults. SSW induced by room-temperature filtered water (RTFW) for comparison across temperature variations: warm water (40°C) and iced water; tonicity: Distilled water and hypertonic saline (36% NaCl); pH variations: acidic and alkaline solution; oily medium: soybean oil; or pressure: immersion under hydrostatic pressure (30 cm water column). To evaluate the influence of sympathetic activity, SSW was assessed under caffeine stimulation: 30 min after ingestion of 60 mg caffeine (Ristretto espresso); diurnal variation: testing at 10 a.m. versus 10 p.m.; or ischemic influence: under sub-systolic ischemia induced by an arm cuff. Additionally, 12 participants underwent 10 min fingertip exposures to EMLA and room-temperature vinegar for comparison.

Results: The time to reach grade III SSW under RTFW varied widely across the sample (from 2.1 to 37.0 min). The acidic solution reduced the time to SSW compared to RTFW (mean: 6.4 vs. 13.9 min; p < 0.01), with a more pronounced effect observed with a warm (40°C) acidic solution (4.0 vs. 15.5 min; p < 0.01). Hot water, distilled water, and 30 cm hydrostatic pressure stimulation shortened the time to SSW compared to RTFW (p < 0.01). No SSW was observed after 30 min of immersion in the oily medium, iced water, alkaline solution, hypertonic solution, or following ischemia. A circadian influence on SSW was also observed, with morning measurements resulting in a faster response than at night (10.4 vs. 14.6 min; p < 0.01). SSW was also accelerated after coffee consumption (6.1 vs. 10.5 min; p < 0.01). After 10 min of stimulation with either EMLA or vinegar, 75% of participants reached grade III SSW (p = 1.00).

Conclusion: SSW is influenced by multiple factors, including solution temperature, pH, osmolarity, hydrostatic pressure, caffeine ingestion, and circadian timing. Warm vinegar elicited a faster and more consistent SSW response compared to other tested conditions, highlighting its use in experimental settings. No difference in SSW was observed between room-temperature vinegar and EMLA after 10 min, supporting its potential for clinical application.

Introduction: Sleep fragmentation (SF) is a hallmark of sleep disorders and has been associated with systemic health issues, but its specific impact on skin health remains unclear. This study aimed to investigate whether SF impairs skin barrier function and identify the biological pathways involved in SF-induced skin damage.

Methods: Twenty-four 6-week-old male BALB/c mice were divided into home cage control (HC) and SF groups. SF was induced using a commercially available SF chamber. Skin barrier function was assessed by measuring transepidermal water loss (TEWL) at 4 and 8 weeks. Epidermal thickness and dermal collagen density were also measured. Total RNA sequencing (RNA-Seq) and bioinformatics analysis were conducted to identify the affected pathways.

Results: TEWL was significantly higher in the SF group than in the HC group at 8 weeks. Epidermal thickness and dermal collagen density were significantly lower in the SF group than in the HC group. In the SF group, 133 differentially expressed genes were identified, of which 14 were upregulated and 119 were downregulated. RNA-Seq and bioinformatics analysis revealed an altered fatty acid metabolism pathway in the skin of mice subjected to chronic SF. This was validated through quantitative real-time polymerase chain reaction.

Conclusion: SF caused physiological and histological changes in the skin, altering the fatty acid metabolism pathway. The role of this pathway in SF-induced skin damage requires further exploration.

Introduction: A new method for conducting in vitro release testing (IVRT) was developed by adapting Higuchi's square root approximation for use with UV-Vis spectrophotometry, and over the counter hydrocortisone formulations at 0.5% and 1.0% concentrations. This IVRT method was investigated for the required validation elements as specified by abbreviated new drug applications (ANDAs) and USP General Chapter <1724> for linearity and range, precision and reproducibility, and discrimination sensitivity, specificity, and selectivity.

Methods: IVRT kinetic experiments were conducted using UV-Vis spectrophotometer, a quartz cuvette, with measurements collected every 15 s for 5 min, and methanol as the receptor solution. Six measurements of the 1% hydrocortisone formulation were conducted over 3 different days, for a total of 18 measurements. The 0.5% formulation was measured 6 times over 1 day. Release rates were obtained by plotting the slope of Abs₂₄₂ vs. √t. HPLC was used to demonstrate specificity via an alternate analytical technique and to show membrane inertness.

Results: The hydrocortisone cream formulations demonstrated specificity via HPLC compared to a USP traceable hydrocortisone reference standard. IVRT sensitivity and selectivity were demonstrated by the statistically different release rates (slopes) of the 0.5% vs. the 1% hydrocortisone formulations at 90% confidence interval (75-133.33%). Linearity throughout the duration of the assay was demonstrated through a r2 value of ≥0.97 for each experiment and for each formulation. All intra-run and inter-run precision calculations relating to the IVRT experiments had %CV values of ≤15%.

Conclusion: IVRT experiments were conducted using UV-Vis spectrophotometry kinetic monitoring of 0.5% and 1% hydrocortisone formulations. This IVRT method was validated for specificity, selectivity, sensitivity, linearity and range, precision and reproducibility following the guidance for ANDAs and USP General Chapter <1724>, thus demonstrating the capability of UV-Vis spectrophotometry as a reliable way of discerning release rates of semisolid formulations. This novel approach can be conducted in a matter of minutes as opposed to hours, a vast improvement over conventional IVRT studies.

Background: Human life is based on oxygen respiration and an enzymatic, free radical-dependent water chemistry, whose billions of parallel reactions take place at pH ∼7.4 and a temperature of 37°C, in accordance with the laws of chemistry. The cellular metabolic processes occur over time periods covered by the half-lives of reactive oxygen species (ROS) for °OH to over 10 s for lipid oxygen species (LOS), indicating that mixtures of free radicals form the basic components for these processes.

Summary: The main source of radicals is the mitochondrial conversion of 1-5% oxygen into "primary" ROS and "secondary" LOS. Every endogenous and exogenous radical generation, triggered by "natural background radiation," "natural environment," or "solar radiation" leads to qualitatively similar mixtures of "primary" ROS and "secondary" LOS or RNS (reactive nitrogen species). A Multilevel Antioxidant Regulation, Repair and Protection System (MARRPS) keeps these radical mixtures in a steady state. Depending on the total number of free radicals, different areas of radical action are defined. The Free Radical Ground State (FRGS) with "homeostasis" and "adaptive homeostasis," the Free Radical Threshold Value (FRTV), and Free Radical Pathological Conditions (FRPC). The quantitative ratio ROS > LOS comprehensively characterizes the "'homeostasis" and "adaptive homeostasis" area of the FRGS. The total number of free radicals cannot be measured directly in the "homeostasis" area. "Adaptive homeostasis" is achieved when excess radicals are stable produced beyond "homeostasis" of the FRGS. The quantity that remains controllable in this range is a maximum of ∼3.58 × 1012 radicals/mg, the value of the body constant FRTV. The sensitized MARRPS provides "semi-stable homeostatic" states characterized by dual stability with ROS > LOS and a stable total ROS/LOS and RNS count beyond the basal FRGS "homeostasis." If the total number of all radicals exceeds the FRTV, where LOS > ROS, this initiates uncontrolled radical chain reactions. The partial failure of the MARRPS in the FRPC area leads to pathological processes which are the starting point for a hundred different diseases.

Key messages: The universal body constant FRTV is the basis for all regular life processes. The design principle described by this simple model applies universally to all aerobic life.

Introduction: Emulsifiers are common excipients in dermal products stabilizing formulations such as creams and emulsions. But due to their potential for skin irritation, emulsifiers for pharmaceutical use should be tested regarding their tolerability before introducing them to the skin of patients. In this study, a systematic investigation with six oil in water-emulsifiers was performed on the forearms of 12 healthy human volunteers, six female, and six male.

Methods: We analyzed the effects of pharmaceutical emulsifiers on the macroscopic skin health parameters measured as trans-epidermal water loss (TEWL) and skin hydration and measured the ceramide profile of the treated skin sites using liquid chromatography coupled to mass spectrometry in order to assess the skin tolerability of the investigated emulsifiers. In a second step, a Partial Least Squares Regression was employed to investigate relationships between changes in the ceramide profile to changes in the TEWL of skin treated with a nonionic as well as an anionic emulsifier.

Results: Skin health measurements showed that the applied emulsifiers inflicted no significant changes compared to the water-treated sample, demonstrating a remarkable skin tolerability. The employed regression model showed a good fit as well as adequate prediction and identified ceramide species associated with impaired skin barrier function. Furthermore, it was found that the relationship between the ceramide profile and the skin barrier function in emulsifier-induced skin damage shows distinct similarities to the interplay of ceramides and skin barrier function in lesional skin linked to atopic dermatitis, hinting toward a common underlying mechanism and opening up possibilities to simulate disease-related changes to the skin for the development of skin damage models.

Conclusion: In conclusion, these detailed investigations yield insight into possible mechanisms of emulsifier-induced skin damage and show its versatility in the investigation of pharmaceutical emulsifiers for formulation development as well as basic research.