Skin Pharmacology and Physiology最新文献

Introduction: Heparin is a commonly used anti-coagulant administered either by intravenous or subcutaneous injection for a systemic effect or topically for the treatment of peripheral vascular disorders.

Objective: This study aimed to formulate heparin in non-ionic colloidal carrier systems (CCSs) having enhanced percutaneous absorption for systemic and topical administration.

Methods: Five CCSs were developed and characterized for their rheological properties, droplet size, and drug loading. The percutaneous absorption of heparin was evaluated in vitro using Franz diffusion cells with rats' skin and with the aid of a developed high-pressure chromatography method. Furthermore, the efficacy of two developed heparin CCSs was tested percutaneously in rats by measuring the response against the time in comparison to subcutaneous administration.

Results: The rheograms and droplet size measurements showed that the developed drug delivery systems have Newtonian properties with a droplet size between 109 and 460 nm. As much as 500 mg of heparin could be loaded in around 5 mL of CCS. Furthermore, using Franz diffusion cells, a diffusion rate of 19.216 ± 2.01 USP U/cm2.h could be achieved for heparin-loaded CCSs. Moreover, the estimated percutaneous in vivo relative bioavailability in comparison to subcutaneous administration could reflect that at least more than 50% of the drug passed through the skin.

Conclusion: The developed novel non-toxic CCSs containing heparin can be good candidates for percutaneous administration as alternative delivery systems for subcutaneous and intravenous invasive administration.

Introduction: Tumor necrosis factor (TNF)-α released after follicular injury such as that caused by plucking plays a role in the activation of hair regeneration. Microneedle (MN) treatment is applied to the scalp to increase permeability and facilitate the delivery of any number of compounds. Because the MN treatment causes injury to the epidermis, albeit minor, we reasoned that this treatment would lead to a temporary TNF-α surge and thereby promote hair regeneration.

Methods: To investigate the effects of MN-treatment-induced microinjury and TNF-α on hair growth, we used C57BL/6N mice which were divided into six experimental groups: three groups of 1) negative control (NC), 2) plucking positive control (PK), and 3) MN therapy system (MTS) mice; and three groups identical to above were treated with a TNF-α blocker for 3 weeks: 4) NCB, 5) PKB, and 6) MTSB group.

Results: After injury, TNF-α surge occurred on day 3 in the PK group and on day 6 in the MTS group. Wnt proteins and VEGF expression were markedly increased in the PK group on day 3 and on day 6 in the MTS group compared to the NC group. Following wound healing, only MTS and PK groups displayed thickened epidermis and longer HF length. Within the 2 weeks following treatment, the rate of hair growth was much slower in the injured mice treated with the TNF-α blocker.

Conclusion: Our findings indicate that microinjury stimulates the wound-healing mechanism via TNF-α/Wnt/VEGF surge to induce hair growth, and that blocking TNF-α inhibits this growth process.

Introduction: The use of epicutaneously applied permethrin in the treatment of common scabies is considered to be the first-line therapy. Due to increasing clinical treatment failure, the development of genetic resistance to permethrin in Sarcoptes scabiei var. hominis has been postulated. In addition, metabolic resistance and pharmacokinetic limitations by parasitic digestion and reactive thickening of stratum corneum are suspected to cause a reduction in cutaneous bioavailability.

Methods: Since lipophilic permethrin is known to form hydrophobic interactions with proteins via van der Waals interactions, a similar interaction was assumed and investigated for permethrin and the protein keratin. Using keratin particles extracted from animal material, a model for hyperkeratotic and parasitic digested scabies skin was developed. Using fluorescence-labeled keratin and ³H-permethrin, their interaction potential was validated by loading and unloading experiments. Additionally, the impact of keratin to permethrin penetration was investigated based on an in vitro model using Franz diffusion cells.

Results: For the first time, keratin particles were introduced as a model for dyskeratotic skin, as we were able to show, the keratin particles' interaction potential with permethrin but no penetration behavior into the stratum corneum. Moreover, comparative penetration experiments of a reference formulation with and without added keratin or keratin-adherent permethrin showed that keratin causes a steal effect for permethrin, leading to a relevant reduction in cutaneous bioavailability in the target compartment.

Conclusion: The results provide further evidence for a relevant pharmacokinetic influencing factor in the epicutaneous application of permethrin and a rationale for the necessity of keratolytic pretreatment in hyperkeratotic skin for the effective use of topical permethrin application in scabies.

Introduction: Folliculitis is a painful infection and inflammation of the hair follicles, mostly caused by bacterial, fungal, or, more rarely, viral infections. Turpentine derivatives have been used traditionally to treat various skin infections and could thus also be effective in treating folliculitis. We carried out an open, prospective, randomized, placebo- and comparator-controlled multicenter trial to evaluate the efficacy and safety of an ointment containing pine turpentine oil, larch turpentine, and eucalyptus oil in the treatment of acute folliculitis.

Methods: Seventy outpatients with acute folliculitis were treated with the turpentine ointment, a comparator (povidone iodine solution), or a placebo (Vaseline) for 7 days. Photographs of the affected skin areas were taken by the physicians at four visits and by the patients on a daily basis. Photographs were evaluated by blinded observers. Primary efficacy endpoint was the change in total hair follicle lesion counts. Secondary endpoints included the evolution of the lesion counts in the course of the study, responder rate (improvement of follicle lesions by at least one count), and the patient's global assessment. Safety endpoints were the tolerability of the treatments and adverse event recording.

Results: A decrease of follicle lesions counts was detected for both active treatments but not for placebo, but the differences among groups were not statistically significant. As for the secondary endpoints, the ointment showed statistically significant superiority over placebo for the evolution of the lesions during the course of the study (p = 0.017), the responder rate (p = 0.032), and the subjective efficacy assessment by patients (p = 0.029). All treatments were equally well tolerated, with a similar number of treatment-emergent adverse events.

Conclusion: The turpentine ointment is an effective and safe option for the treatment of folliculitis.

Background: Skin care is a basic, daily activity performed by formal and informal caregivers from birth until end of life. Skin care activities are influenced by different factors, e.g., culture, knowledge, industrial developments and marketing activities. Therefore, various preferences, traditions, and behaviors exist worldwide including skin care of neonates and infants. The objective of this scoping review was to obtain an overview about the evidence of skin care activities in neonates and infants. Studies from 2010 were eligible if the population was (skin) healthy neonates and infants; if the concept was skin care interventions; and if the context was at home, in a community setting, in a pediatric outpatient service, or in a hospital. We searched for the literature via OVID in MEDLINE and Embase, in the Cochrane Library, in trial registries and for gray literature.

Summary: We identified 42 studies since 2010, which examined four main skin care interventions: bathing, wiping, washing, and topical application of leave-on products. Details of interventions were often not reported, and if they were, they were not comparable. The four skin care interventions focused on 13 different care goals, mainly prevention of skin diseases, maintaining skin barrier function, and improving (skin) health. We evaluated effects of skin care interventions using 57 different outcome domains; 39 of 57 were skin-related and 18 were not. Mostly, laboratory or instrumental measurements were used.

Key messages: Our scoping review identified four skin care interventions with a broad heterogeneity of product categories and application details. Studies in skin care interventions should include all relevant information about product category and application details to ensure comparability of study results. This would be helpful in developing recommendations for formal and informal caregivers. We identified 13 skin care goals. "Maintaining healthy skin/skin barrier function/skin barrier integrity," "prevention of atopic dermatitis," "cleansing," and "improving skin barrier function" were most often allocated to skin care interventions. There is substantial variability regarding outcome domains in skin care research. Our results support the need of developing core outcome sets in the field of skin care in healthy skin, especially in this age-group of neonates and infants.

Background: A disruption of sebocyte differentiation and lipogenesis has fatal consequences and can cause a wide spectrum of skin diseases, from acne vulgaris to sebaceous carcinoma, however, the relevant molecular mechanisms have not been fully clarified.

Objectives: The induction of autophagy and apoptosis in human sebocytes in response to biologically relevant fatty acids was investigated.

Methods: Free fatty acids (arachidonic acid, linoleic acid, palmitic acid, and palmitoleic acid) and the pan-caspase inhibitor QVD-Oph were added to the supernatant of cultured human SZ95 sebocytes. Individual relevant proteins were analyzed by Western blotting. Apoptosis and cell viability were determined, and typical autophagy structures were detected through electron microscopy. To obtain cell growth curves, cell confluence was continuously monitored by real-time cell analysis.

Results: Fatty acids induced the development of intracellular lipid droplets with subsequent apoptosis, whereas arachidonic acid caused the most rapid effect. Cleavage products of caspase-3 were only detected in arachidonic acid-induced apoptosis. The high basal apoptotic rate of cultured SZ95 sebocytes was strongly suppressed by QVD-Oph. Fatty acid-induced apoptosis was also markedly inhibited by QVD-Oph, whereas intracellular lipid droplets further accumulated. While cell viability after incubation with linoleic acid, palmitic acid, or palmitoleic acid and QVD-Oph was comparable with that of non-treated controls, arachidonic acid significantly reduced cell viability and cell density despite the concomitant pan-caspase inhibitor treatment. Using electron microscopy, typical autophagy structures were detected, such as autophagosomes and autolysosomes, at the basal level, which became more pronounced after treatment with fatty acids.

Conclusions: Our findings contribute to a better understanding of the inflammation-associated mechanisms of lipogenesis and cell death induction in human sebocytes and may help to unveil the effects of fatty acid-rich human nutrition.

Introduction: Rosacea is a common, facial, chronic inflammatory skin disease. Due to its complex pathogenesis, adequate therapy of rosacea can be challenging. An innovative recent therapeutic tool is cold atmospheric plasma (CAP), which is already established in the treatment of chronic wounds and promising in different other skin diseases.

Methods: In a split-face pilot study we investigated dielectric-barrier-discharged CAP in erythemato-telangiectatic (ETR) and/or papulopustular rosacea (PPR). CAP treatment was applied on lesional skin of a randomized side once daily (90 s/area) for 6 weeks. The other untreated side served as control. Co-primary endpoints were ≥1 improvement of the Investigator Global Assessment (IGA) score on the treated side compared to control and a decline of the Dermatology Life Quality Index (DLQI) after 6 weeks. Secondary endpoints included inflammatory lesion count (papules and pustules), skin redness intensity and erythema size. Adverse events (AEs) were recorded constantly. Additionally, participants were weekly assessed for symptoms, skin condition, trigger factors, skin care, treatment success, and local tolerance parameters. All p values were calculated using the Wilcoxon signed-rank test.

Results: Twelve subjects (ETR, n = 3; ETR and PPR, n = 9) completed the study. DLQI was significantly improved after 6 weeks (p = 0.007). On the CAP-treated side, lesions (p = 0.007) and erythema size (p = 0.041) were significantly reduced compared to the control. IGA (p = 0.2) and skin redness intensity (p = 0.5) did not differ significantly between control and CAP-treated side. No serious AEs occurred and treatment was well tolerated.

Conclusion: CAP is a promising new treatment of rosacea, especially for PPR.

Introduction: Compared to adults, newborns' skin has a thinner epidermis and stratum corneum with decreased hydration levels, higher transepidermal water loss, and a pH variation between 5.5 and 7.5. These characteristics can predispose to the occurrence of dryness, infections, and dermatological conditions. Water and liquid soap with adequate formulation have shown to be beneficial and safe for newborns' skin. However, studies evaluating the effect of bar soap, products widely used in Brazil and Latin America, are unknown. Therefore, the objective of this study was to compare the effects of liquid and bar soaps on the term newborns' skin.

Methods: This randomized controlled, parallel, single-blind clinical trial was conducted at a public university hospital in São Paulo, Brazil. 100 healthy term newborns with no congenital anomalies, acute diseases, or dermatological conditions were randomized to use liquid soap (experimental group) or bar soap (control group). Skin pH, transepidermal water loss, stratum corneum hydration, sebum content, and skin condition were assessed before and after the first bath, at 48 h, 14 days, and 28 days after birth. These evaluations were performed on the forearm, abdomen, buttocks, and thigh. In addition, the mother's perception of soap use was also evaluated.

Results: Data of 100 newborns were analyzed by intention to treat. The rate of retention was 53%. Newborns exposed to the liquid soap presented significantly better skin acidification (p < 0.001) and significantly better stratum corneum hydration (p < 0.001) than the skin of newborns exposed to the bar soap, regardless of the area evaluated. There were no significant differences in transepidermal water loss, sebum content, dryness, erythema, or skin breakdown and the mother's perceptions of the use of the soaps.

Conclusion: Newborns in the experimental group presented better skin acidification and stratum corneum hydration when compared to newborns in the control group.

Introduction: Atopic dermatitis (AD) is a physical, emotional, and social burden for patients. Most suffer from itching, pain, and dry skin as well as sleep disturbances, experienced stigmatization, anxiety, or depression. Therefore, it is important to consider the psychosocial well-being and also stigmatization in the treatment of people with AD. The aims of this study were to compare clinical and psychosocial parameters between patients with a different severity of AD and to analyse the effect of an omega-6-fatty-acid-skin therapy.

Methods: Adult patients with clinically confirmed AD were asked about quality of life, stigmatization, and well-being after dermatological diagnosis. A second examination took place after 2-5 weeks. Meanwhile, after randomization, half of the patients used an omega-6-fatty-acid-skin therapy.

Results: Seventy-nine patients were included in the study. The use of omega-6-fatty-acid-skin therapy resulted in a significant reduction in the severity of xerosis cutis compared to patients using another basic therapy. In addition, the health-related quality of life of all patients improved significantly in both groups (F = 7.56; p = 0.008), and no significant difference was found between the groups over time in the patient-reported outcomes.

Conclusion: Basic therapy for AD leads to relevant improvements in clinical status as well as quality of life. Patients using omega-6-fatty-acid-skin therapy experience greater improvement in xerosis cutis compared to free-choice basic therapy.