Skin Pharmacology and Physiology最新文献

Confocal Raman microspectroscopy is widely used in dermatology and cosmetology for analysis of the concentration of skin components (lipids, natural moisturizing factor molecules, water) and the penetration depth of cosmetic/medical formulations in the human stratum corneum (SC) in vivo. In recent years, it was shown that confocal Raman microspectroscopy can also be used for noninvasive in vivo depth-dependent determination of the physiological parameters of the SC, such as lamellar and lateral organization of intercellular lipids (ICLs), folding properties of keratin, water mobility, and hydrogen bonding states. The results showed that the strongest skin barrier function, which is primarily manifested by the orthorhombic organization of ICLs, is provided at ≈20-40% SC depth, which is related to the maximal bonding state of water with surrounding components in the SC. The secondary and tertiary structures of keratin determine water binding in the SC, which is depth-dependent. This paper shows the technical possibility and advantage of confocal Raman microspectroscopy in noninvasive investigation of the skin and summarizes recent results on in vivo investigation of the human SC.

Introduction: Skin injury and wound healing is an inevitable event during lifetime. However, several complications may hamper the regeneration of the cutaneous tissue and lead to a chronic profile that prolongs patient recovery. Platelet-rich plasma is rising as an effective and safe alternative to the management of wounds. However, this technology presents some limitations such as the need for repeated blood extractions and health-care interventions.

Objective: The aim of this study was to assess the use of an endogenous and storable topical serum (ES) derived from plasma rich in growth factors promoting wound healing, and to obtain preliminary data regarding its clinical and experimental effect over ulcerated skin models and patient care.

Methods: Human dermal fibroblast and 3D organotypic ulcerated skin models were used to assess ES over the main mechanisms of wound healing including cell migration, edge contraction, collagen synthesis, tissue damage, extracellular matrix remodeling, cell death, metabolic activity, and histomorphometry analysis. Additionally, 4 patients suffering from skin wounds were treated and clinically assessed.

Results: ES promoted dermal fibroblast migration, wound edge contraction, and collagen synthesis. When topically applied, ES increased collagen and elastin deposition and reduced tissue damage. The interstitial edema, structural integrity, and cell activity were also maintained, and apoptotic levels were reduced. Patients suffering from hard-to-heal wounds of different etiologies were treated with ES, and the ulcers healed completely within few weeks with no reported adverse events.

Conclusion: This preliminary study suggests that ES might promote cutaneous wound healing and may be useful for accelerating the re-epithelization of skin ulcers.

Introduction: With its large surface area, skin facilitates a topical administration of active ingredients, and thus percutaneous delivery to a specific target site. Due to its high barrier function and different diffusion characteristics, skin governs the efficacy of these active ingredients and a bioavailability in the epidermal and dermal tissue.

Objective: In order to characterize the vertical and lateral movement of molecules into and inside the skin, the diffusivity of active ingredients with different physicochemical properties and their penetration ability in different dermal skin layers was investigated.

Methods: A novel lateral dermal microdialysis (MD) penetration setup was used to compare the diffusion characteristics of active ingredients into superficial and deep-implanted MD membranes in porcine skin. The corresponding membrane depth was determined via ultrasound and the active ingredients concentration via high-pressure liquid chromatography measurement.

Results: The depth depended penetration of superficial and deep-implanted MD membranes and the quantitative diffusivity of two active ingredients was compared. An experimental lateral MD setup was used to determine the influence of percutaneous skin penetration characteristics of an active ingredient with different lipophilic and hydrophilic characteristics. Therefore, hydrophilic caffeine and lipophilic LIP1, which have an identical molecular weight but different lipophilic characteristics, were tested for their penetration ability inside a propylene glycol and oleic acid formulation.

Conclusion: The vertical and lateral penetration movement of caffeine was found to exceed that of LIP1 through the hydrophilic dermal environment. The findings of this study show that the lipophilicity of active ingredients influences the penetration movement and that skin enables a conical increasing lateral diffusivity and transdermal delivery.

Introduction: Proactive therapy with topical corticosteroids (TCSs) is the standard treatment for chronic inflammatory diseases such as atopic dermatitis; however, skin atrophy as TCS side effect remains a concern.

Methods: This 16-week, evaluator-blinded, within-patient placebo-controlled, randomized study enrolled volunteers with healthy skin conditions. For 12 weeks, their volar forearm and the back of their hand were applied with hydrocortisone acetate 1% cream (HC), methylprednisolone aceponate 0.1% cream (MPA), betamethasone valerate 0.1% cream (BMV), or an active agent-free base cream (Dermatop® Basiscreme) once daily twice weekly, and pimecrolimus 1% cream (PIM) twice daily twice weekly. Epidermal and dermal thickness was measured by optical coherence tomography and high-frequency ultrasound, respectively. Furthermore, skin atrophy and telangiectasia were determined by contact dermatoscopic photography (Dermaphot®).

Results: After 8 and 12 weeks, only BMV led to significant epidermal thinning on both sites. Four weeks after the end of treatment, epidermal thickness returned to baseline. No dermal thinning, atrophy, or telangiectasia was observed.

Conclusions: MPA, HC, and PIM may be more suitable for repeated and prolonged treatment, especially in chronic diseases.

Purpose: Surgery within radiated tissue is associated with increased complication rates. It is hypothesized that impaired wound healing may result from aberrant inflammatory responses that occur in previously radiated tissues. Previous work has demonstrated that the topical application of naturally occurring antigen α-gal (Galα1-3Galβ1-(3)4GlcNAc-R) nanoparticles (AGNs) within wounds accelerates macrophage recruitment and subsequent healing in both normal and diabetic wounds. Herein, we hypothesize that application of this antigen would similarly enhance wound healing in irradiated tissues.

Methods: To simulate human physiology, α-1,3-galactosyltransferase knockout (KO) mice were exposed to the antigen to produce anti-α-gal antibodies (anti-Gal). Ten days prior to wounding, the dorsal skin was irradiated with 1 session of 40 Gy. Bilateral dorsal 6-mm splinted full-thickness wounds were created within the radiated skin and treated with 50 µL of AGNs (50 mg/mL) immediately after wounding and again on postoperative day 1. A control KO group underwent similar irradiation and wounding protocols but was treated with phosphate-buffered saline (PBS) vehicle. Wild-type (WT) mice, which do not produce anti-Gal, went through the same irradiation and wounding.

Results: Histologic analysis demonstrated enhanced epithelial migration in the radiated/AGN-treated KO wounds, which was significantly elevated in comparison to radiated/PBS-treated KO wounds beginning by day 15 and continuing until the end of the study (p < 0.01). In WT mice, treatment with AGNs showed no effect on epithelial migration.

Conclusions: Topical application of AGNs onto irradiated wounds significantly ameliorates the delayed wound healing classically seen in radiated skin and results in faster wound closure with only transient application.

Introduction: We aim to explore potentials and modalities of cold atmospheric pressure plasma (CAP) for the subsequent development of therapies targeting an increased perfusion of the lower leg skin tissue. In this study, we addressed the question whether the microcirculation enhancement is restricted to the tissue in direct contact with plasma or if adjacent tissue might also benefit.

Methods: A dielectric barrier discharge (DBD)-generated CAP device exhibiting an electrode area of 27.5 cm2 was used to treat the anterior lower leg of ten healthy subjects for 4.5 min. Subsequently, hyperspectral imaging was performed to measure the tempospatially resolved characteristics of microcirculation parameters in superficial (up to 1 mm) and deeper (up to 5 mm) skin layers.

Results: In the tissue area covered by the plasma electrode, DBD-CAP treatment enhances most of the perfusion parameters. The maximum oxygen saturation increase reached 8%, the near-infrared perfusion index (NIR) increased by a maximum of 4%, and the maximum tissue hemoglobin increase equaled 14%. Tissue water index (TWI) was lower in both the control and the plasma groups, thus not affected by the DBD-CAP treatment. Yet, our study reveals that adjacent tissue is hardly affected by the enhancements in the electrode area, and the effects are locally confined.

Conclusion: Application of DBD-CAP to the lower leg resulted in enhancement of cutaneous microcirculation that extended 1 h beyond the treatment period with localization to the tissue area in direct contact with the cold plasma. This suggests the possibility of tailoring application schemes for topically confined enhancement of skin microcirculation, e.g., in the treatment of chronic wounds.

Introduction: The human lower limb is widely used as a model to study in vivo microcirculatory physiology and pathophysiology. It is a preferential target for critical comorbidities (overweight, diabetes, and peripheral vascular disease). Movement and activity are consistently regarded as beneficial, but the related adaptive physiology is still poorly understood. Our goal was to better identify the foot microcirculatory changes after a regular walking gait activity in healthy subjects of different ages.

Methods: Twelve healthy participants of both sexes, with normal BMI and Ankle-Brachial Index, were selected and grouped according to age - group I (21.0 ± 1 y.o.) and group II (55.8 ± 3 y.o.). The protocol involved 2 phases of 5-min duration each - phase 1, a static standing position, and phase 2, 5-min walking with a comfortable pace on a pre-established circuit. Perfusion changes were assessed in the dorsal region of both feet before (baseline, phase 1) and after (phase 2) the gait period by noninvasive optical technologies - laser Doppler flowmetry (LDF), photoplethysmography, and polarized spectroscopy (PSp). Comparative statistics were performed with a 95% confidence level.

Results: All instruments detected an asymmetric nonsignificant perfusion between right and left feet during rest in all participants with values in females consistently lower than men. Older participants exhibited lower baseline values than the younger group. Gait evoked a perfusion reduction in all participants relative to phase 1 detected with all technologies, with statistically significant changes recorded with LDF (group I, p = 0.033, and group II, p = 0.028) and PSp (group II, p = 0.041). Furthermore, LDF revealed that gait significantly reduced perfusion velocity in the older group (p = 0.003). Corresponding changes in the younger group were present but discrete. Recovery to baseline levels was also slower in the older group.

Discussion/conclusions: Our results confirm that perfusion is age dependent and demonstrate the clinical relevance of simple dynamic activities such as gait. This reduction of the dorsal foot perfusion occurs in depth, being more pronounced with the movement intensity, suggesting a wide application potential in early diagnostics as for rehabilitation.

Introduction: Seborrhea or oily skin has been one of the most common complaints affecting both men and women physically and psychologically. Chitosan is a biopolymer obtained from the alkaline deacetylation of chitin. Due to its positively charged nature, chitosan can effectively bind to lipids. Therefore, chitosan nanoparticle (CN) formulation may benefit in the reduction of skin sebum.

Objective: The aim of this study was to evaluate the efficacy and safety of CN formulation in the reduction of skin sebum.

Method: The study was a randomized, double-blinded, placebo-controlled trial in 24 participants aged 18-40 years with clinical seborrhea. Participants were randomly assigned to apply the CN and gum (CN-G) or placebo (gum alone) twice daily for 4 weeks. Sebum level, corneometry, transepidermal water loss (TEWL), and clinical seborrhea grading were evaluated at baseline and week 2 and 4.

Results: In the T-zone, sebum levels in the CN-G group were significantly lower than the placebo group at week 4 (p = 0.043), while for the U-zone, sebum levels were not different between groups. There were no statistical differences in corneometry and TEWL at any visit. Although the clinical seborrhea grading in CN-G was lower, it was not significantly different from the placebo. A few cases reported mild and self-limiting scaling and acneiform eruption.

Conclusion: The CN-G gel could significantly reduce sebum levels on seborrhea patients with acceptable safety profiles.