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Introduction: Non-invasive measurement of the stratum corneum hydration (SCH) with capacitance-based instrumentation is established in dermatological and cosmetic studies. We wanted to test the reliability of non-invasive self-measurements for SCH performed under real-life conditions by volunteers with a Bluetooth-based (wireless) probe Corneometer® (CM 825i) transmitting the data via a smartphone application to a central server. Probes and smartphones communicated using Bluetooth Low Energy. Data from the smartphone were securely transferred to a remote server in a different country with TLS encryption using HTTPS protocols. CM 825i values were correlated with the established CM 825 under laboratory conditions. The primary endpoint was the correlation of the two probes. Secondary endpoints were the coefficient of variation (CV) and delta values (before and after treatment). Methods: Eighteen healthy volunteers (f: 8; m: 10) participated in the prospective observational study. The real-world home use of the wireless CM 825i was performed before and after treatments with base cream DAC for 7 days. Results: Both instruments showed a significant and relevant correlation (p < 0.0001; Spearman coefficient of r = 0.8647). CM 825i and CM 825 differentiate significantly between normal and high SCH. Both devices showed comparable robustness in repeated measurements with a CV between 5.6% and 9.2%. Conclusion: We could show a significant correlation between both devices and a comparable differentiation between low and high SCH and comparable CVs. The real-life use demonstrated adequate acquiring and transmitting of in vivo data to a smartphone and subsequently transmitting to the secure server with low numbers of missed transmissions (<0.2%) and missed measurements (<5%). [ABSTRACT FROM AUTHOR]

The stratum corneum (SC)--the outermost layer of the epidermis--is the principal permeability and protective barrier of the skin. Different components of the SC, including corneocytes, natural moisturizing factor, a variety of enzymes and their inhibitors, antimicrobial peptides and lipids, work interactively to maintain barrier function. The main barrier properties of the SC are the limitation of water loss and the prevention of infection and contact with potentially harmful exogenous factors. Although the SC functions consistently as a protective barrier throughout the body, variations in functions and morphology occur across body sites with age and skin type. Healthy SC function also depends on the interplay between the chemosensory barrier, the skin's microbiome and the innate immune system. Dysregulation of SC barrier function can lead to the development of skin disorders, such as dry, flaky or sensitive skin, but the complete underlying pathophysiology of these are not fully understood. This review provides insight into the current literature and emerging themes related to epidermal barrier changes that occur in the context of dry, flaky and sensitive skin. Additional studies are needed to further elucidate the underlying aetiology of dry, flaky and sensitive skin and to provide tailored treatment. [ABSTRACT FROM AUTHOR]

Introduction: Along with climate changes, we see an increase in allergic symptoms and the number of pollen-allergic patients in many countries. Increased allergic symptoms are associated with an elevated ozone exposure which may be linked by impaired epithelial barrier function. This study aimed to quantify the clinical effect of ozone and pollen double exposure (DE). We tested whether ozone impairs barrier-related skin physiology and mucosal functions under DE with pollen in grass pollen-allergic patients versus healthy controls. Methods: This case-control study included 8 grass pollen-allergic patients and 8 non-allergic healthy subjects exposed to grass pollen and ozone in the GA2LEN pollen chamber, comparing shorter and longer DE duration. Non-invasive skin physiological parameters were assessed, including stratum corneum hydration, skin redness, surface pH, and basal transepidermal water loss as a parameter for epidermal barrier function. The subjects' general well-being, bronchial, nasal, and ocular symptoms were documented. Results: Skin physiology tests revealed that DE in allergic patients deteriorates the epidermal barrier function and increases the surface pH and skin redness. DE significantly induced nasal secretion in pollen-allergic versus healthy subjects, which was more pronounced with longer DE. The general well-being was significantly impaired under DE versus pollen or ozone alone, with a negative influence of DE duration. No relevant bronchial symptoms were recorded. Conclusion: Skin physiology and nasal mucosal symptoms are negatively affected by ozone and grass pollen DE in allergic patients. The negative effects showed, in some parameters, a dose (time)-response relationship. The pH can be regarded as a possible modulatory mechanism. [ABSTRACT FROM AUTHOR]

The multiple protective functions of the skin derive from the interactions between epithelial skin and immune cells as well as the commensal microbiota. Developed in the last trimester of intra‐uterine life, the skin barrier adapts dynamically after birth. Specific differences in the structure and physiology have been disclosed between infant and adult skin. The stratum corneum of infants is thinner and structured by thicker corneocytes with a more anisotropic surface in comparison to adult skin. Lower levels of the natural moisturizing factor and its constituents, together with the increased protease activity in the epidermis result in dry baby skin and ongoing adaptation of the desquamation to the extra‐uterine environment. Infant epidermis is characterized by an accelerated proliferation rate and clinically competent permeability barrier in term neonates, despite the higher baseline values of transepidermal water loss in infants. The skin surface of newborns is less acidic, which could increase susceptibility to diaper and atopic dermatitis. Immediately after birth, skin is colonized by commensal bacteria—a process dependent on the mode of delivery and of major importance for the maturation of the immune system. Skin bacterial diversity and dysbiosis have been related to different pathology such as atopic and seborrheic dermatitis. This paper focuses on the ongoing structural, functional and biochemical adaptation of the human skin barrier after birth. We discuss the interactions on the 'skin barrier/ microbiota/ immune system' axis and their role in the development of competent functional integrity of the epidermal barrier. [ABSTRACT FROM AUTHOR]

Background: Instrumentation technology for transepidermal water loss measurements has not been substantially modified since its introduction by Nilsson in 1977. Recent progress in sensor development allowed a new sensor arrangement using a matrix of 30 sensors. Raw measurement values are processed with spatial statistical analysis. We aimed to compare the new, multi‐sensor probe (Tewameter TM Hex) with the established Tewameter TM 300 probe and to gain reference data for the new parameters of transepidermal energy loss and water vapor concentration on skin. Material and methods: Baseline measurements and repeated measurements on the volar forearm and assessment on eight different anatomical locations were performed on 24 healthy volunteers (both gender) with the TM Hex and the TM 300. Results: A significant correlation (p < 0.001; R‐coefficient = 0.9) between TM Hex and the TM 300 with a low coefficient of variance (CV) 11% for TM Hex and 19% for TM 300, could be assessed. The CV ranged between 7% (right inner upper arm) and 14% (palms). Average transepidermal heat loss ranged from 12 W/m2 on the lower leg to 38.8 W/m2 on the palm. Conclusion: The correlation between TM Hex and TM 300 along with the robustness of the measurements with the TM Hex shows that the new probe for assessment of epidermal barrier function is comparable to the TM 300. In most conditions, TM Hex provides more accurate measurements than TM 300. New parameters open the field to studying skin's water and energy balance. [ABSTRACT FROM AUTHOR]

Introduction: Skin microbiome and skin physiology are important indicators of the epidermal homeostasis status. Stress models can reveal pathological conditions and modulating effects. Here we investigated the cutaneous microbiome in relation to skin physiology after mild tape stripping (TS) without treatment compared to two cosmetic leave-on lotions (pH 5.5 vs. pH 9.3) in 25 healthy volunteers. Methods: The microbiome was analyzed by 16S-rRNA-gene amplicon sequencing and put in relation to the following skin physiology parameter: epidermal barrier function (TEWA-Meter TM300), stratum corneum hydration (Corneometer CM 825), surface pH (pH-Meter), and skin erythema (Mexameter). Results: TS reduced the alpha diversity with a recovery over 7 days without treatment. Both lotions significantly accelerated the recovery of the alpha diversity already after 2 days with a slightly higher rate for the acidic lotion. After TS, the relative abundance of Proteobacteria was increased, whereas Actinobacteria were reduced. The relative abundances of typical skin-associated genera were reduced after TS. Taxa compositions returned to normal levels after 7 days in all treatment groups. An accelerated normalization could be observed with both lotions already after 2 days. A significant difference in skin pH was observed on day 2 and day 7 with an increased pH for the alkaline lotion. Both lotions induced an increase in stratum corneum hydration. Conclusion: The study proved the suitability of an experimental stress model in the assessment of skin surface microbiome in relation to skin physiology. Stratum corneum hydration increased significantly with both lotions already at day 2. Microbiome parameters (alpha diversity, mean relative taxa, abundance of selected genera) normalized over 2–7 days. The following mechanisms could be responsible for the accelerated normalization of the microbiome: (a) optimized hydration during the recovery phase, (b) the composition of the lotion, (c) the induced repair mechanism. Thus, the formulation has a positive effect on the stratum corneum hydration and subsequently on cutaneous microbiome and skin physiology. Furthermore, this eventually has implications on the modulation of exogenous stress-induced epidermal alterations. [ABSTRACT FROM AUTHOR]

Purpose of Review: Atopy is defined as the genetic predisposition to react with type I allergic diseases such as food‐, skin‐, and respiratory allergies. Distinct molecular mechanisms have been described, including the known Th2 driven immune response. IL‐17A (IL‐17) is mainly produced by Th17 cells and belongs to the IL‐17 family of cytokines, IL‐17A to F. While IL‐17 plays a major role in inflammatory and autoimmune disorders, more data was published in recent years elucidating the role of IL‐17 in allergic diseases. The present study aimed to elaborate specifically the role of IL‐17 in atopy. Methods: A systematic literature search was conducted in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials, regarding IL‐17 and atopy/allergic diseases. Results: In total, 31 novel publications could be identified (food allergy n = 3, allergic asthma n = 7, allergic rhinitis [AR] n = 10, atopic dermatitis [AD] n = 11). In all allergic diseases, the IL‐17 pathway has been investigated. Serum IL‐17 was elevated in all allergic diseases. In AR, serum and nasal IL‐17 levels correlated with the severity of the disease. In food allergies, serum IL‐17E was also elevated in children. In AD, there is a trend for higher IL‐17 values in the serum and skin specimen, while it is more expressed in acute lesions. In allergic asthma, serum IL‐17 levels were increased. In two studies, higher serum IL‐17 levels were found in severe persistent asthmatic patients than in intermittent asthmatics or healthy controls. Only one therapeutic clinical study exists on allergic diseases (asthma patients) using a monoclonal antibody against the IL‐17 receptor A. No clinical efficacy was found in the total study population, except for a subgroup of patients with (post‐bronchodilator) high reversibility. Summary: The role of IL 17 in the pathogenesis of allergic diseases is evident, but the involvement of the Th17 cytokine in the pathophysiological pathway is not conclusively defined. IL‐17 is most likely relevant and will be a clinical target in subgroups of patients. The current data indicates that IL‐17 is elevated more often in acute and severe forms of allergic diseases. [ABSTRACT FROM AUTHOR]

Biomechanics of the skin is an important subject in skin research. It has been studied for many decades involving various technologies and methods to characterize and quantify mechanical properties of the skin under different in vivo conditions. The present EEMCO paper reviews the current rel-evant information, providing practical orientation to researchers dedicated to in vivo assessment of biomechanics of skin and its annexes. We discuss the available non-invasive instruments, including their principles and variables. A correspondence between the descriptors nomenclature proposed by Agache and the designation for the suction-based standard instruments is proposed. The addressed properties include skin softness/stiffness, firmness, elasticity, elastic and viscoelastic properties, extensibility, resilience, anisotropy, acoustical shock wave hardness, friction (in relation to topographic properties), thickness, fiber/stress mechanics (bending, cyclic, tensile, fatigue, or torsion), and hardness. We provide the relation of these properties to biomechanical descriptors and in some cases to SI units. Practical guidance for the proper use of these instruments, limitations, and possible interpretations are provided, while discussing the meaning of descriptive or "phenomenological" variables. For studies intended to quantify the effect of an intervention with regard to mechanical properties, we recommend a minimum of 30–40 participants, based on normal distribution of the data sets. Some important limitations are recognized, including the lack of standardization of procedures and calibration of instruments, which compromises the relevance and real nature of the descriptors/parameters obtained with these devices. The present work highlights an approach to a better practice and a science-supported biomechanical assessment of human skin, hair, and nails. [ABSTRACT FROM AUTHOR]

In recent years, the importance of the microbiome in maintaining healthy skin has become apparent. Both the classic microbiology cultivation techniques used since the early 1970s and the next-generation sequencing procedures refined in the past decade reveal the importance of skin microbiome in healthy and diseased skin. To strengthen and eventually restore a healthy microbiome in patients with dermatological conditions like atopic dermatitis (AD), it is important to consider the factors that influence the composition of the microbiome, such as skin pH and skin barrier integrity. Moreover, targeting the microbiome may support established treatment regimens in years to come. Initial studies have generated promising results, suggesting that AD treatments, including select emollients and topical corticosteroids, have a positive impact on the microbiome. This paper reviews different aspects of microbiome in AD and their implications in clinical practice. [ABSTRACT FROM AUTHOR]

Background: There is a lack of real-life safety data on treatment options for chronic urticaria in the presence of comedication and comorbidities. Methods: We present a single-center UCARE pilot study of 212 outpatients with chronic urticaria. Patients were divided into three groups according to different CU therapies according to international guidelines. Results: Of 212 patients, 108 (mean age 48.9years, 71.3% female) had 59 comorbidities, including cardiovascular, autoimmune and malignant diseases. Patients were followed for a mean of 24.6months (SD ± 21.3). Urticaria therapies were divided into three groups: A: 105 (97.2%) with omalizumab and 2nd generation antihistamines), B: 16 patients (14.8%): dual therapy with antihistamines and cyclosporine in 10 (9.3%), montelukast in five (4. 6%), dapsone in four (3.7%), hydroxychloroquine in one patient (0.9%), C: 12 (11.1%) patients received a third drug for 4.9months (SD ± 3.2) and one quadruple therapy (2.1months). 10 out of 12 (83.3%) patients received montelukast, two (16.7%) cyclosporine, two (16.7%) dapsone and one (8.3%) hydroxychloroquine as a third drug for chronic urticaria. Conclusions: Combining treatment modalities for chronic urticaria and comorbidities are available and feasible with a good safety profile. [ABSTRACT FROM AUTHOR]

Abstract: The intact skin represents a barrier to the uncontrolled loss of water, proteins, and plasma components from the organism. Owing to its complex structure, the epidermal barrier with its major layer, the stratum corneum, is the rate-limiting unit for the penetration of exogenous substances through the skin. The epidermal barrier is not a static structure. The status of different functions of the epidermis can be monitored by assessing specific biophysical parameters such as transepidermal water loss, stratum corneum hydration, and skin surface pH. Variables originating from the individual as well as exogenous factors have an important influence on the epidermal barrier parameters. [Copyright &y& Elsevier]

The antimicrobial treatment of wounds is still a major problem. Tissue-tolerable electrical plasma (TTP) is a new approach for topical microbial disinfection of the skin surface. The aim of the present study was to investigate the influence of TTP on a carotenoid profile in relation to skin physiology parameters (epidermal barrier function, stratum corneum (SC) hydration, surface temperature and irritation parameters). We were interested in the interaction of TTP and the antioxidative network, as well as the consequences for skin physiology parameters. These parameters are also indicative of TTP safety in vivo. For plasma application, 'Kinpen 09' was used (surface exposure 30-43°C) for 3 s. Beta-carotene and water profiles were assessed by in vivo Raman microspectroscopy (skin composition analyzer 3510). Skin physiology parameters were measured with Tewameter TM 300, Corneometer CM 825, skin thermometer and Chromameter CR 300. All parameters were assessed non-invasively on seven healthy volunteers before and after plasma application in vivo. We could show that TTP application leads to a decrease in beta-carotene especially in the superficial SC. Skin-surface temperature increased by 1.74°C, while the transepidermal water loss (TEWL) increase indicated an impaired barrier function. SC hydration decreased as seen in water profile especially in the superficial layers and capacitance values. A slight increase in skin redness was measurable. The induction of reactive oxygen species is probably the major contributor of TTP efficacy in skin disinfection. Skin physiology parameters were influenced without damaging the skin or skin functions, indicating the safety of TTP under in vivo conditions. [ABSTRACT FROM AUTHOR]

Abstract: Background: High doses of sun-emitted UV-radiation induce reactive oxygen species (ROS) as major pro-oxidants thus inducing premature skin aging. The best prevention of the destructive action of free radicals in human skin is textile coverings, topical sunscreens and the development of a high antioxidative protective network. Objective: The effects of topical, systemic and combined application of antioxidants (AO) were investigated on human skin in vivo. Methods: Topical application of creams and systemic incorporation of tablets both containing AO was investigated in vivo by resonance Raman spectroscopy. Results: Topical, systemic and combined AO-treatments induced a statistically significant increase of AO levels in human skin while placebo did not show any changes. The highest accumulation was induced by the combination of topical and systemic AO. Carotenoid-tablets combined with placebo-cream induced less carotenoid accumulation than carotenoid-tablets alone. Carotenoid levelling after the end of treatment lasted for around 2weeks following the topical application of AOs, and up to 5weeks after systemic administration, depending on the BMI of volunteers. Conclusion: Topically applied AO are stored in the SC for a short time only due to the rapid AO-depletion by desquamation, textile contact, washing and environmental stress. In contrast to topical application, the systemically applied carotenoids are stored in the body fat tissue and slowly released onto the skin surface with sweat and sebum. The combined topical and systemic application of AO represents an optimal form of protection of the AO-network. [Copyright &y& Elsevier]

The influence of stress factors on human skin induces the production of free radicals. Free radicals react immediately with antioxidants contained in the skin, giving rise to their depletion and with the surrounding molecules, resulting in their damage, disorganization and even destruction. High amounts of free radicals are produced in the upper skin layers, i.e. mainly in the epidermis, subsequent to sun irradiation. Irradiation of the skin in the infra-red (IR) range of the spectra, applied at physiological doses, can produce free radicals. The magnitude of destruction of antioxidants, such as carotenoids, can serve as a marker of the extent of the stress factor, characterized by the quantity of produced free radicals. In this study, measurements on the degradation of cutaneous carotenoids following IR skin irradiation of 12 healthy volunteers (skin type II), with two IR sources (standard infrared radiator = SIR and water filter infrared = wIRA) were taken using resonance Raman spectroscopy. Topical application of the antioxidant beta-carotene (2 mg/cm) provided protection for the human skin when exposed to IR radiation. The magnitude of the degradation of dermal carotenoids after IR irradiation was significantly higher for SIR than for wIRA irradiation, for both non-treated and cream-treated skin areas. The amount of destroyed carotenoids after IR irradiation was higher in the case of pretreatment with beta-carotene than for the untreated skin, indicating that the superficial part of antioxidants is most important for protecting against external stressors. The direct comparison of beta-carotene content was significantly higher for the cream-treated compared to untreated areas for all pairs: baseline, wIRA, after wIRA, baseline SIR and after SIR. Additionally, topically applied carotenoids as a single antioxidant component are less stable than the carotenoids in the skin incorporated by nutrition and accumulated in a mixture with different antioxidant substances. Resonance Raman spectroscopy can be used for the non-invasive measurements of carotenoids, which can be rated as marker substances of redox processes. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Silver-loaded seaweed-based cellulosic fibre improves epidermal skin physiology in atopic dermatitis: safety assessment, mode of action and controlled, randomized single-blinded exploratory in vivo study. Experimental Dermatology 2010; 19: e9-e15. Abstract Background: The epidermal part of the skin is the major interface between the internal body and the external environment. The skin has a specific physiology and is to different degrees adapted for protection against multiple exogenous stress factors. Clothing is the material with the longest and most intensive contact to human skin. It plays a critical role especially in inflammatory dermatoses or skin conditions with an increased susceptibility of bacterial and fungal infections like atopic dermatitis. Previously, we have shown a dose-dependent antibacterial and antifungal activity of silver-loaded seaweed-based cellulosic fibres. Aim of the study: We studied the mode of action of silver-loaded seaweed-based cellulosic fiber and performed a broad safety assessment. The principal aim was to analyse the effects of wearing the textile on epidermal skin physiology in 37 patients with atopic dermatitis in a controlled, randomized single-blinded in vivo study. Furthermore, the sensitization potential was tested in a patch test in 111 panellists. Results: We could demonstrate in vitro a dose-dependent scavenging of induced reactive oxygen species by silver-loaded seaweed-based cellulosic fibers. Safety assessment of these fibres showed no detectable release of silver ions. Furthermore, ex vivo assessment after 24 h application both in healthy volunteers and patients with atopic dermatitis by sequential tape stripping and subsequently raster electron microscopy and energy dispersive microanalysis analysis revealed no detectable amounts of silver in any of stratum corneum layers. Serum analysis of silver showed no detectable levels. The in vivo patch testing of 111 volunteers revealed no sensitization against different SeaCell® Active (SeaCell GmbH, Rudolstadt, Germany) containing fabrics. The in vivo study on 37 patients with known atopic dermatitis and mild-to-moderate eczema on their arms were randomly assigned to either silver-loaded seaweed fibre T-shirts or to cotton T-shirts for 8 weeks. A significant reduction in Staphylococcus aureus colonization was detectable for the silver T-shirts compared with cotton T-shirts without any changes in non-pathogenic surface bacteria colonization. Furthermore, a more pronounced improvement in barrier function (transepidermal water loss) was observed in mildly involved eczema areas during the first 4 weeks of the study. Stratum corneum hydration and surface pH improved in both treatment groups over time. Conclusion: The tested silver-loaded seaweed fibre can be regarded as safe and seams to be suited for application in bio-active textiles in atopic dermatitis based on its positive in vivo activity. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which discusses the study on the function of filaggrin-histidine-urocanic acid cascade in the acidification of stratum corneum.

Please cite this paper as: Functional skin adaptation in infancy – almost complete but not fully competent. Experimental Dermatology 2010; 19: 483–492. Early postnatal life is a period of active functional reorganization and cutaneous physiological adaptation to the extrauterine environment. Skin as the outermost organ of mammalians is endowed of multiple functions such as protection, secretion, absorption and thermoregulation. Birth stimulates the epidermal barrier maturation and the skin surface acidification especially in premature infants. In full-term infants the developed stratum corneum accomplishes competent barrier function, in contrast to prematures. Complete barrier maturation in preterm infants is fulfilled by 2–4 weeks of the postnatal life. However, in preterms with 23–25 weeks gestational age this process takes longer. Versatile regulatory mechanisms, namely skin surface acidity, calcium ion gradient and nuclear hormone receptors/ligands are interrelated in the complex postnatal newborn adaptation. The skin of newborns is adjusting quickly to the challenging environmental conditions of the postpartum. However, certain functions, for example, microcirculation, continue to develop even beyond the neonatal period, that is, up to the age of 14–17 weeks. Different environmental factors (for instance, dry and cold climate, diapers and cosmetic care procedures) influence the postnatal development of skin functional parameters such as stratum corneum hydration and the permeability barrier especially in premature infants. The aim of this article is to summarize the current knowledge on skin physiology in newborn and infants with a practical approach and to discuss the possible clinical consequences. This review offers the readership a critical and practical overview of skin physiology in newborns and infants. It emphasizes possible new research fields in neonatal and infantile skin physiology. [ABSTRACT FROM AUTHOR]

Background: The cutaneous antioxidants form an efficient protection system against the destructive potential of free radicals, produced by environmental factors, such as UV-sun irradiation, hazardous substances and lifestyle habits. Most of the antioxidants cannot be produced by the human organism. Thus, they have to be incorporated by food and beverages. Material and Methods: In the present manuscript, the distribution of carotenoids as a marker for antioxidative potential in human skin was investigated with two different in vivo Raman spectroscopy methods with an excitation wavelength of 785 nm (Skin Analyzer) and at 488 nm (resonance Raman spectroscopy). The carotenoid profile was assessed at three different anatomical locations (palm, forehead and volar forearm) in 12 healthy volunteers. Results: In untreated skin, the major fraction of the carotenoids is located in the upper part of the stratum corneum (SC). The amount of carotenoid is lower in the upper part of the SC on the forearm compared to forehead and palm shown with both methods. Both methods detect similar distinction patterns of carotenoid levels for the three anatomical locations. Conclusion: The present study supports the hypothesis that antioxidative substances; here carotenoids, are secreted via eccrine sweat glands and/or sebaceous glands to the skin surface. Raman spectroscopic methods are an efficient tool to analyze the distribution of carotenoids in the human skin over time and with the Skin Analyzer over different layers of the epidermis. Resonance Raman spectroscopy is suited to analyze deeper parts of the skin. [ABSTRACT FROM AUTHOR]

Previous studies have shown that pH declines from between 6 and 7 at birth to adult levels (pH 5.0–5.5) over 5–6 days in neonatal rat stratum corneum (SC). As a result, at birth, neonatal epidermis displays decreased permeability barrier homeostasis and SC integrity, improving days 5–6. We determined here whether peroxisome proliferator-activated receptor (PPAR) activators accelerate postnatal SC acidification. Topical treatment with two different PPARα activators, clofibrate and WY14643, accelerated the postnatal decline in SC surface pH, whereas treatment with PPARγ activators did not and a PPARβ/δ activator had only a modest effect. Treatment with clofibrate significantly accelerated normalization of barrier function. The morphological basis for the improvement in barrier function in PPARα-treated animals includes accelerated secretion of lamellar bodies and enhanced, postsecretory processing of secreted lamellar body contents into mature lamellar membranes. Activity of β-glucocerebrosidase increased after PPARα-activator treatment. PPARα activator also improved SC integrity, which correlated with an increase in corneodesmosome density and increased desmoglein-1 content, with a decline in serine protease activity. Topical treatment of newborn animals with a PPARα activator increased secretory phospholipase A2 activity, which likely accounts for accelerated SC acidification. Thus, PPARα activators accelerate neonatal SC acidification, in parallel with improved permeability homeostasis and SC integrity/cohesion. Hence, PPARα activators might be useful to prevent or treat certain common neonatal dermatoses.Journal of Investigative Dermatology (2009) 129, 365–374; doi:10.1038/jid.2008.218; published online 14 August 2008 [ABSTRACT FROM AUTHOR]

Abstract: Emollients, moisturizers, and keratolytic agents are essential in the topical treatment of psoriasis. They are adjuvants for classic treatments and help to reduce the scale load of individual patients. The major role for emollients and moisturizers is the supportive role in normalizing hyperproliferation, differentiation, and apoptosis; furthermore, they exert anti-inflammatory effects, for example, through physiologic lipids. Subsequently, an improved barrier function and stratum corneum hydration makes the epidermis more resistant to external stressors and reduces the induction of Koebner phenomena. Most of the emollients are lipid-rich (sometimes oily). The keratolytic agents, especially salicylic acid, and higher concentration of urea should be used in the initial keratolytic phase, whereas moisturizing products and emollients are especially suitable in the intermediate phase and the chronic/remission phase of psoriasis. They should be combined with bath oils. [Copyright &y& Elsevier]

Permeability barrier function is measured with instruments that assess transepidermal water loss (TEWL), either with closed- or open-loop systems. Yet, the validity of TEWL as a measure of barrier status has been questioned recently. Hence, we tested the validity of this measure by comparing TEWL across a wide range of perturbations, with a variety of methods, and in a variety of models. TEWL rates with two closed-chamber systems (VapoMeter and H4300) and one closed-loop system (MEECO) under different experimental in vivo conditions were compared with data from four open-loop instruments, i.e. TM 210, TM 300, DermaLab and EP 1. The instruments were compared in vivo both in humans and hairless mice skin subjected to different degrees of acute barrier disruption. The values obtained with bioengineering systems were correlated with absolute water loss rates, determined gravimetrically. Measurements with both closed and open systems correlated not only with each other, but each method detected different degrees of barrier dysfunction. Although all instruments differentiated among gradations in TEWL in the mid-range of barrier disruption in vivo, differences in very low and very high levels of disruption were less accurately measured with the H4300 and DermaLab systems. Nevertheless, a high Pearson correlation coefficient ( r) was calculated for data from all instruments vs. gravimetrically assessed TEWL. Together, these results verify the utility of TEWL as a measure of permeability barrier status. Moreover, all tested instruments are reliable tools for the assessment of variations in permeability barrier function. [ABSTRACT FROM AUTHOR]

In neonatal rat stratum corneum (SC), pH declines from pH 6.8 at birth to adult levels (pH 5.0–5.5) over 5–6 d. Liver X receptor (LXR) activators stimulate keratinocyte differentiation, improve permeability barrier homeostasis, and accelerate the in utero development of the SC. In this manuscript we determined the effect of LXR activators on SC acidification in the neonatal period and whether these activators correct the functional abnormalities in permeability barrier homeostasis and SC integrity/cohesion. Formation of the acid SC-buffer system was accelerated by topically applying the LXR activator, 22( R)-hydroxycholesterol, and non-oxysterol activators of LXR, TO-901317, and GW-3965. A sterol which does not activate LXR had no effect. LXR activation increased secretory phospholipase A2 (sPLA2) activity and conversely, inhibition of sPLA2 activity prevented the LXR induced increase in SC acidification, suggesting that increasing sPLA2 accounts in part, for the LXR stimulation of acidification. LXR activation resulted in an improvement in permeability barrier homeostasis, associated with an increased maturation of lamellar membranes attributable to an increased β-glucocerebrosidase activity. SC integrity cohesion also normalized in LXR-activator-treated animals and was associated with an increase in corneodesmosomes and in desmoglein 1 expression. These results demonstrate that LXR activators stimulate the formation of an acidic SC and improve both permeability barrier homeostasis and SC integrity/cohesion. [ABSTRACT FROM AUTHOR]

At birth, neonatal stratum corneum (SC) pH is close to neutral but acidifies with maturation, which can be ascribed, in part, to secretory phospholipase A2 and sodium/hydrogen antiporter 1 (NHE1) activities. Here we assessed the functional consequences of a neutral SC pH in a newborn rat model. While basal transepidermal water loss rates are near normal, barrier recovery (BR) rates after acute barrier disruption were delayed in newborn animals. The abnormality in barrier homeostasis could be improved by topical applications of an acidic buffer, indicating that barrier abnormality is primarily due to high SC pH. The delay in BR correlated with incompletely processed lamellar membranes and decreased activity of beta-glucocerebrosidase. Inhibition of NHE1 delayed BR after acute barrier perturbation. SC integrity was abnormal in newborn animals. Electron microscopy demonstrated decreased corneodesmosomes (CD) in newborn animals with decreased expression of desmoglein 1 and corneodesmosin. Serine protease activation appears to be responsible for CD degradation in newborn animals, because serine protease activity is increased in the SC and it can be reduced by acidification of the SC. The delay in acidification of neonatal SC results in abnormalities in permeability barrier homeostasis and SC integrity and are likely due to pH-induced modulations in enzyme activity. [ABSTRACT FROM AUTHOR]

Although loricrin is the predominant protein of the cornified envelope (CE) in keratinocytes, loss or gain of loricrin function in mouse models produces only modest skin phenotypes. In contrast, insertional mutations resulting in a frameshift in the C-terminal domain of loricrin produce the characteristic ichthyosis of loricrin keratoderma in mouse and man. To ascertain the basis for the loricrin keratoderma phenotype, we assessed epidermal structure and stratum corneum (SC) function in a previously genotyped human loricrin keratoderma kindred. Our studies revealed abnormal corneocyte fragility and basal permeability barrier function, but accelerated repair kinetics. Despite fragility, increased water loss occurred predominantly via extracellular domains, which correlated with disorganized lamellar bilayers that were linked spatially to discontinuities of the CE. Accelerated barrier recovery was explicable by amplified lamellar body secretion, while partial normalization of the CE in the outer SC correlated with persistence of abundant calcium in the extracellular spaces (positioned to activate transglutaminase-1). These results show that the barrier abnormality in loricrin keratoderma is linked to a defective CE scaffold, resulting in increased extracellular permeability, as shown previously for another "scaffold disorder", lamellar ichthyosis. But in contrast to lamellar ichthyosis, the CE scaffold partially normalizes in the outer SC in loricrin keratoderma. [ABSTRACT FROM AUTHOR]

At birth, human stratum corneum (SC) displays a near-neutral surface pH, which declines over several days to weeks to months to an acidic pH, comparable to that of adults. Recent studies suggest that an acidic pH is required for normal permeability barrier homeostasis and SC integrity/cohesion. We assessed here the basis for postnatal acidification in the neonatal rat, where SC pH, as measured with a flat surface electrode, declines progressively from near-neutral levels (pH 6.63) on postnatal days 0 to 1 to adult levels (pH 5.9) or even below over the subsequent 7 to 8 d. The postnatal decline in SC pH was paralleled by a progressive activation of a pH-dependent hydrolytic enzyme, β-glucocerebrosidase. Because SC acidification could not be linked to commonly implicated exogenous factors, such as bacterial colonization, or the deposition of sebaceous gland products. We next assessed whether changes in one or more of three endogenous mechanisms demonstrate postnatal activity changes that contribute to the progressive development of an acidic SC pH. Although the histidine-to-urocanic acid pathway has been implicated in acidification of the adult SC, surface pH is completely normal in histidase-deficient (his/his, Peruvian) mice, ruling out a requirement for this mechanism. In contrast, when sodium/hydrogen antiporter-1 (NHE1), which predominantly acidifies membrane domains at the stratum granulosum–SC interface, is inhibited, postnatal acidification of the SC is partially blocked. Likewise, SC secretory phospholipase A2 (sPLA2) activity, measured with a fluorometric assay, is low at birth, but increases progressively (by 66%) over the first 5 d after birth, and inhibition of sPLA2 between days 0 to 1 and days 5 to 6 delays postnatal SC acidification. Together, these results describe a neonatal model, in which the development of an acidic surface pH can be ascribed, in part, to progressive SC acidification by two endogenous mechanisms, namely, sPLA2 and NHE1, which are known to be important for acidification of adult rodent SC. Conversely, the impaired acidification of neonatal SC, which has important functional and clinical consequences, can be explained by the relatively low activities of one or both of these mechanisms at birth. [ABSTRACT FROM AUTHOR]

The only known function of human sebaceous glands is the provocation of acne. We assessed here whether sebum influences stratum corneum hydration or permeability barrier function in asebia J1 and 2 J mice, with profound sebaceous gland hypoplasia. Asebia J1 mice showed normal permeability barrier homeostasis and extracellular lamellar membrane structures, but they displayed epidermal hyperplasia, inflammation, and decreased (>50%) stratum corneum hydration, associated with a reduction in sebaceous gland lipids (wax diesters/monoesters, sterol esters). The triglyceride content of both asebia and control stratum corneum was low, consistent with high rates of triglyceride hydrolysis within the normal pilosebaceous apparatus, despite high rates of triglyceride synthesis. Although a mixture of synthetic, sebum-like lipids (sterol/wax esters, triglycerides) did not restore normal stratum corneum hydration to asebia skin, topical glycerol, the putative product of triglyceride hydrolysis in sebaceous glands, normalized stratum corneum hydration, and the glycerol content of asebia stratum corneum was 85% lower than in normal stratum corneum. In contrast, another potent endogenous humectant (urea) did not correct the abnormality. The importance of glycerol generation from triglyceride in sebaceous glands for stratum corneum hydration was demonstrated further by (i) the absence of sebaceous-gland-associated lipase activity in asebia mice, whereas abundant enzyme activity was present in the glands of control mice; and (ii) the inability of high concentrations of topical triglyceride to correct the hydration abnormality, despite the presence of abundant lipase activity in asebia stratum corneum. These results show that sebaceous-gland-derived glycerol is a major contributor to stratum corneum hydration. [ABSTRACT FROM AUTHOR]

Prolonged exposure of human epidermis to excess endogenous or exogenous glucocorticoids can result in well-recognized cutaneous abnormalities. Here, we determined whether short-term glucocorticoid treatment would also display adverse effects, specifically on two key epidermal functions, permeability barrier homeostasis and stratum corneum integrity and cohesion, and the basis for such changes. In humans 3 d of treatment with a potent, commonly employed topical glucocorticoid (clobetasol), applied topically, produced a deterioration in barrier homeostasis, characterized by delayed barrier recovery and abnormal stratum corneum integrity (rate of barrier disruption with tape strippings) and stratum corneum cohesion (μg protein removed per stripping). Short-term systemic and topical glucocorticoid produced similar functional defects in mice, where the basis for these abnormalities was explored further. Both the production and secretion of lamellar bodies were profoundly decreased in topical glucocorticoid-treated mice resulting in decreased extracellular lamellar bilayers. These structural changes, in turn, were attributable to a profound global inhibition of lipid synthesis, demonstrated both in epidermis and in cultured human keratinocytes. The basis for the abnormality in stratum corneum integrity and cohesion was a diminution in the density of corneodesmosomes in the lower stratum corneum. We next performed topical replacement studies to determine whether lipid deficiency accounts for the glucocorticoid-induced functional abnormalities. The abnormalities in both permeability barrier homeostasis and stratum corneum integrity were corrected by topical applications of an equimolar distribution of free fatty acids, cholesterol, and ceramides, indicating that glucocorticoid-induced inhibition of epidermal lipid synthesis accounts for the derangements in both cutaneous barrier function and stratum corneum integrity/cohesion. These studies indicate that even... [ABSTRACT FROM AUTHOR]

There is evidence that the “acid mantle” of the stratum corneum is important for both permeability barrier formation and cutaneous antimicrobial defense. The origin of the acidic pH of the stratum corneum remains conjectural, however. Both passive (e.g., eccrine/sebaceous secretions, proteolytic) and active (e.g., proton pumps) mechanisms have been proposed. We assessed here whether the free fatty acid pool, which is derived from phospholipase-mediated hydrolysis of phospholipids during cornification, contributes to stratum corneum acidification and function. Topical applications of two chemically unrelated secretory phospholipase sPLA2 inhibitors, bromphenacylbromide and 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol, for 3 d produced an increase in the pH of murine skin surface that was paralleled not only by a permeability barrier abnormality but also altered stratum corneum integrity (number of strippings required to break the barrier) and decreased stratum corneum cohesion (protein weight removed per stripping). Not only stratum corneum pH but also all of the functional abnormalities normalized when either palmitic, stearic, or linoleic acids were coapplied with the inhibitors. Moreover, exposure of intact murine stratum corneum to a neutral pH for as little as 3 h produced comparable abnormalities in stratum corneum integrity and cohesion, and further amplified the inhibitor-induced functional alterations. Furthermore, short-term applications of an acidic pH buffer to inhibitor-treated skin also reversed the abnormalities in stratum corneum integrity and cohesion, despite the ongoing decrease in free fatty acid levels. Finally, the secretory-phospholipase-inhibitor-induced alterations in integrity/cohesion were in accordance with premature dissolution of desmosomes, demonstrated both by electron microscopy and by reduced desmoglein 1 levels in the stratum corneum (shown by immunofluorescence staining and vizualized by confocal microscopy). Together, these results demonstrate: (i) the importance of phospholipid-to-free-fatty-acid processing for normal stratum corneum acidification; and (ii) the potentially important role of this pathway not only for barrier homeostasis but also for the dual functions of stratum corneum integrity and cohesion. [ABSTRACT FROM AUTHOR]

Part II. Presents information on a study which compared five instruments used in measuring stratum corneum hydration in vivo. Measurement of different anatomical sites; Moisture-accumulation test results; Sorption-desorption test results.

Part I. Presents information on a study which compared five instruments used in measuring stratum corneum hydration in vitro. Depth of the electrical measurement; Effects of solutions with different dielectric constants; In vitro sorption-desorption test on filter paper.

The article presents the case reports of a 7-year old boy with generalized prutitic skin lesions. It relates that after a histologic examination of a biopsy, the skin lesions were diagnosed as cutaneous mastocytosis characterized by a proliferation and accumulation of mast cells in different body tissues. Moreover, it discusses the treatment procedure to cure pediatric manifestation of cutaneous mastocytosis.

Discusses several facts about standardized washing models. Characteristics of surfactants in modern cleansing products; Mechanisms that induce the dermatological effects of surfactants; Approaches used in washing protocols; Comparison between home application and controlled laboratory application.

The effects of air pollution on health are gaining increasing research interest with limited data on skin alterations available. It was suggested that air pollution is a trigger factor for sensitive skin (SS). However, this data was based on surveys with a lack of experimental data. SS is related to altered skin nerve endings and cutaneous neurogenic inflammation. TTe present study was to assess the in vitro effect of particulate matter (PM) on epidermis and nerve ending homeostasis. PM samples were collected according to a validated protocol. Reconstructed human epidermis (RHE, Episkin®) was exposed to PM and subsequently the supernatants were transferred to a culture of PC12 cells differentiated into sensory neurons (SN). Cell viability, axonal growth and neuropeptide‐release were measured. The modulation of the expression of different inflammatory, keratinocytes differentiation and neurites growth markers was assessed. PM samples contained a high proportion of particles with a size below 1 μm and a complex chemical composition. Transcriptomic and immunohistochemical analyses revealed that PM altered keratinocytes terminal differentiation and induced an inflammatory response. While viability and functionality of the SN were not modified, their outgrowth was significantly decreased after incubation with PM‐exposed Episkin® supernatants. This was closely related to the modification of nerve growth factor/semaphorin 3A balance. This study showed that air pollutants have negative effects on keratinocytes and sensory nerve endings including inflammatory responses. These effects are probably involved in the SS pathophysiology and might be involved in inflammatory skin disorders. [ABSTRACT FROM AUTHOR]

Sensitive skin is commonly assessed on the basis of self-reports from patients, and sometimes questionnaires, such as the Sensitive Scale-10, are used. The severity of sensitive skin follows a continuum, from the absence of sensitive skin to very sensitive skin. The aims of this cross-sectional study were to compare subjects with and without symptomatic sensitive skin and to propose diagnostic criteria for sensitive skin. A total of 160 women, between 18 and 65 years of age, with and without sensitive skin, and without any associated skin diseases, were recruited. Mean age was 41 years old. Fifty-five percent of participants reported having “very sensitive” or “sensitive” skin. In the sensitive skin group, the participants mainly experienced skin irritability (100%), tautness (97.5%), discomfort (90%) and redness (90%). According to the receiver operating characteristic curve, a Sensitive Scale-10 (SS-10) cut-off value of 12.7 can be used to detect sensitive skin (with a sensitivity of 72.4% and specificity of 90.3%). [ABSTRACT FROM AUTHOR]

Polidocanol is a local anaesthetic and antipruritic compound that is used in the treatment of itching skin conditions such as eczema. Its mechanisms of action are largely ill defined. This study has compared the antipruritic efficacy of topical polidocanol in histamine-induced itch and a histamine-independent, cowhage-induced model of pruritus. Polidocanol (3%) or vehicle was applied topically under occlusion for 1 h to the forearms of 45 healthy volunteers before itch was provoked by rubbing in 40-45 spicules of cowhage or skin prick testing with 10 mg/ml histamine. Itch was recorded at 1-min intervals for 30 min on a 100-mm visual analogue scale. Polidocanol significantly reduced the area under the curve for cowhage-induced itch by 58% ( P < 0.05), but had no significant effect on histamine-induced itch. This result underlines the importance of histamine-independent itch models in the development of topical antipruritic agents. [ABSTRACT FROM AUTHOR]

No abstract available Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The human organism has developed a protection system against the destructive effect of free radicals. The aim of the present study was to investigate the extent of exogenous stress factors such as disinfectant and IR-A radiation on the skin, and their influence on the kinetics of carotenoids distribution during the recovery process. Ten healthy volunteers were assessed with resonance spectroscopy using an Argon-laser at 488 nm to excite the carotenoids in vivo. Additionally, Raman-confocal-micro-spectroscopy measurements were performed using a model 3510 Skin Composition Analyzer with spatially resolved measurements down to 30 m. The measurements were performed at a baseline of 20, 40, 60, and 120 min after an external stressor consisting either of water-filtered infrared A (wIRA) with 150 mWcm2or 1 mlcm2of an alcoholic disinfectant. Both Raman methods were capable to detect the infrared-induced depletion of carotenoids. Only Raman-microspectroscopy could reveal the carotenoids decrease after topical disinfectant application. The carotenoid-depletion started at the surface. After 60 min, recovery starts at the surface while deeper parts were still depleted. The disinfectant- and wIRA-induced carotenoid depletion in the epidermis recovers from outside to inside and probably delivered by sweat and sebaceous glands. We could show that the Raman microscopic spectroscopy is suited to analyze the carotenoid kinetic of stress effects and recovery. [ABSTRACT FROM AUTHOR]

Background Systemic alteration of interleukin-6 (IL-6) influences peripheral nerve regeneration. We investigated the potential influences of in situ (at the coaptation site) IL-6 modulation in a peripheral-nerve-transection/sciatic-nerve-graft in vivo model. Methods We quantified the elongation of regenerating axons, the number of arborizing axons, and the number of branches per arborizing axon 7 days after the injury in mice expressing axonal fluorescent proteins (thy-1-YFP mice). Sciatic nerves from nonexpressing mice (C57Bl6 or IL-6-/- mice) were grafted into those expressing yellow fluorescent protein. We altered the in situ IL-6 concentration by loading a topical gelatin sponge with an inhibiting IL-6 receptor antibody or IL-6 combined with a soluble IL-6 receptor. Sciatic nerves from IL-6-/- mice were grafted into an additional group. The contralateral sham-operated side served as control in all the groups. Results Axonal elongation increased significantly with the in situ application of the IL-6 receptor antibody, while topical IL-6 significantly reduced the regeneration distance. The number of arborizing axons increased significantly in nerves grafted from IL-6-/- mice, whereas branches per arborizing axons remained stable. Conclusion In situ IL-6 receptor inhibition and IL-6-/- nerve grafting enhance early peripheral nerve regeneration in an acute murine injury model. [ABSTRACT FROM AUTHOR]

Chronic rhinosinusitis (CRS) with (CRSwNP) or without nasal polyps (CRSsNP) is a persistent, heterogeneous inflammatory condition affecting the upper respiratory tract. The present study aimed to improve the characterization of CRS endotypes based on the chemokine and cytokine expression pattern in the CRS tissues. Concentrations of chemokines and cytokines were measured in tissues from nasal biopsies obtained from 66 CRS patients and 25 control subjects using multiplexing or single analyte technologies. Cluster analysis based on the concentration of type-1 (MCP-3/CCL7, MIP-1 α/CCL3), type-2 (IL-5, MCP-3/CCL7, MIP-1 α/CCL3, TARC/CCL17, PARC/CCL18, IP-10/CXCL10, ECP), and type-3 (IL-22) chemokines and cytokines identified six CRS endotypes (clusters). Cluster 1 (type-3) and 2 (type-1) were associated with a low prevalence of nasal polyps, Cluster 3 (type-1, -2, -3) and Cluster 4 (type-2, -3, medium IL-22) with medium, and Cluster 5 (type-2, -3, high Il-22) and Cluster 6 (type-2) with high prevalence of nasal polyps. Asthma was highly prevalent in Cluster-6. Our findings add to the existing knowledge of CRS endotypes and may be useful for the clinical decision-making process. The advancement of biologics therapy for upper respiratory tract disorders rationalizes the personalized diagnostic approach to warrant a successful treatment and monitoring of CRS. [ABSTRACT FROM AUTHOR]

Until recently, itch pathophysiology was poorly understood and treatments were poorly effective in relieving itch. Current progress in our knowledge of the itch processing, the numerous mediators and receptors involved has led to a large variety of possible therapeutic pathways. Currently, inhibitors of IL‐31, IL‐4/13, NK1 receptors, opioids and cannabinoids, JAK, PDE4 or TRP are the main compounds involved in clinical trials. However, many new targets, such as Mas‐related GPCRs and unexpected new pathways need to be also explored. [ABSTRACT FROM AUTHOR]

Abstract: Understanding the penetration behaviour of drugs into human skin is a prerequisite for the rational development and evaluation of effective dermal drug delivery. The general procedure for the acquisition of quantitative drug penetration profiles in human skin is performed by sequential segmentation and extraction. Unfortunately, this technique is destructive, laborious and lacks spatial resolution. Confocal Raman microscopy bares the potential of a chemically selective, label free and nondestructive analysis. However, the acquisition of quantitative drug depth profiles within skin by Raman microscopy is impeded by imponderable signal attenuation inside the tissue. In this study, we present a chemical semi-solid matrix system simulating the optical properties of human skin. This system serves as a skin surrogate for investigation of Raman signal attenuation under controlled conditions. Caffeine was homogeneously incorporated within the skin surrogate, and Raman intensity depth profiles were acquired. A mathematical algorithm describing the Raman signal attenuation within the surrogate was derived from these profiles. Human skin samples were incubated with caffeine, and Raman intensity depth profiles were similarly acquired. The surrogate algorithm was successfully applied to correct the drug profiles in human skin for signal attenuation. For the first time, a mathematical algorithm was established, which allows correction of Raman signal attenuation in human skin, thus facilitating reliable drug quantification in human skin by confocal Raman spectroscopy. [Copyright &y& Elsevier]

Background Optical coherence tomography ( OCT) is a noninvasive imaging technique that uses a low-power infrared laser to image up to 2 mm beneath the skin's surface. Objective To test the feasibility and diagnostic value of using in vivo OCT to define excision margins before Mohs micrographic surgery ( MMS) of basal cell carcinoma (BCC). Methods Patients with biopsy confirmed BCC undergoing MMS were recruited ( n = 52). Excision margins defined by experienced dermatologists were compared with those of OCT-assessed borders and validated with histologic assessments. Results Forty-one (79%) lesions were clear after one MMS procedure; 11 (21%) lesions required a second MMS stage after excision of the clinician-predicted boundary. Generally, the OCT instrument indicated that the estimated clinical margin was 0.4-mm larger than the OCT margin. For lesions requiring a single MMS stage, OCT indicated that lesions were 1.4 ± 1.3 mm smaller than the Mohs excision. Before excision of lesions requiring more than one MMS stage, OCT always indicated that the lesion boundary would extend outside the planned MMS defect boundary. Conclusions The present study shows the prospective utility of using OCT to refine clinically estimated borders for MMS. OCT assessment has the potential to reduce the excised area without compromising the integrity of tumor-free borders. [ABSTRACT FROM AUTHOR]

There are multiple techniques and methods to assess peripheral vascular function in vivo but not without limitations. More discriminative, sensitive and also practical evaluation strategies are needed to fully characterize the peripheral vascular function. In the present work, a new quantitative descriptor, the 'elimination half-life time' was developed from flow-related variables as a non-invasive microcirculatory rate parameter to describe vascular dynamics. Fifty-four healthy volunteers and six type 2 diabetic patients, both genders, were submitted to a dynamical procedure consisting in the inhalation of a 100% saturated atmosphere of oxygen for 10 min. The tcpO2 and microcirculatory blood flow [Laser Doppler Flowmetry (LDF)] were measured in a randomly selected leg with a Periflux 5000 system before, during and after the procedure. A monocompartmental model was adjusted to tcpO2 and LDF data. The tcpO2 constant elimination rate, expressed as the Oxygen elimination half-life, was used as an indicator of the vulnerability of peripheral tissue and compared in healthy versus non-healthy individuals. Under normal conditions, the saturated ventilation increases the tissue's O2 availability, as an expression of the natural capacity to adjust the tissue hemodynamics to new metabolical/perfusion conditions. Diabetic patients are expected to suffer vascular impairment and ischemia. Under O2 overloading conditions, those hypoxic territories tend to uptake all the delivered oxygen, expressed as a significant increase in the O2 elimination half-life. This approach allows to propose 'elimination half-life time' as the first quantitative descriptive parameter combining miogenic, hemodynamic and metabolic aspects of the microcirculatory physiology and to help to identify the individual's vascular vulnerability. [ABSTRACT FROM AUTHOR]

In 1951, Crosti reported on seven patients with ‘reticulo-histiocytoma of the back’ who presented with figurate erythematous plaques and nodules on the back or lateral trunk. Reticulo-histiocytoma of the back was later classified as a primary cutaneous follicle center lymphoma (PCFCL). A definitive diagnosis of the condition is frequently delayed because of a relative lack of clinical symptoms and difficulties in interpretation of the histologic findings. Indeed, a number of primary cutaneous B-cell lymphomas have been mislabeled as pseudolymphomas in the past.We present a case of PCFCL that initially demonstrated predominantly small T lymphocytes on histology. These findings were interpreted as an inflammatory pseudolymphomatous reaction. However, small lymphocytes, whether B or T cells, in early lesions of cutaneous B-cell lymphomas should not automatically be considered ‘reactive.’ Persistent antigenic stimulation of lymphocytes in a neoplastic process or by an antigen, for example, Borrelia burgdorferi, can lead to transformation and cell division with development of large blast cells. In our patient, the initial scarcity of B lymphocytes also led to further diagnostic difficulties.Although the association of primary cutaneous B-cell lymphoma with Borrelia infection is known, there are still difficulties in differentiating the condition from pseudolymphoma. Such difficulties can in part be ascribed to the morphologic changes such lymphomas can undergo over time. The initially small number of B cells that may be seen at first in PCFCL infiltrates may increase in number in longer-standing lesions. It is also important to recognize that inability to verify monoclonality should not exclude the diagnosis of lymphoma. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a systemic inflammatory disease characterized by hindered antioxidant defense and increased formation of free radicals. There are limited data on the skin carotenoids in psoriatic skin as well as their modulation during narrow‐band UVB (NB‐UVB) phototherapy of the disease. Aim: The aim of this prospective study is to reveal the skin carotenoids levels during NB‐UVB phototherapy of psoriasis in humans. Material and methods: Twenty Caucasian subjects with mild‐to‐moderate plaque psoriasis (15m; 5f) were enrolled in the study, and nine gender‐ and age‐matched healthy volunteers were recruited for controls of oxidative stress measurements. All psoriasis patients underwent 10 sessions of NB‐UVB phototherapy. Measurements were taken at baseline and after 10 sessions of NB‐UVB phototherapy. The assessment of carotenoid levels in the skin in vivo was performed by a non‐invasive, reflectance spectroscopy‐based device. Psoriasis severity was assessed by psoriasis area and severity index (PASI). The dermatology life quality index (DLQI) was evaluated in psoriatic patients. Results: Baseline carotenoid levels were significantly lower in psoriasis patients in comparison to healthy controls. NB‐UVB phototherapy insignificantly diminished carotenoid levels in the skin of psoriasis patients, while clinical improvement both in PASI score and DLQI was observed. Conclusion: We showed the levels of skin carotenoids in psoriatic patients are lower than in healthy subjects. NB‐UVB did not change significantly skin carotenoid levels. Further studies should elucidate the potential effect of antioxidants supplementation during NB‐UVB of psoriasis. [ABSTRACT FROM AUTHOR]

Background: The early detection of skin cancer is still challenging and calls for objective, fast diagnostic, and ideally non‐invasive methods in order to leave the potentially malignant tumor cells unaltered. In this paper, the parelectric spectroscopy was applied to evaluate the potential of a non‐invasive detection of basal cell carcinoma (BCC) and malignant melanoma. Materials and Methods: A prototype of parelectric spectroscopy was used to investigate non‐invasively dipole density and mobility of suspicious skin lesions. The differences in investigated tissue were analyzed compared to pathohistological findings in a clinical study on 51 patients with suspected BCC and malignant melanoma. Results: The non‐invasive parelectric spectroscopy could differentiate between normal skin, BCC, and melanoma but failed to distinguish between different types of skin cancer. The data were normalized to unsuspected nearby skin because the different skin locations influence dipole density and mobility. Conclusion: The results of the pilot study indicate that the parelectric spectroscopy might be an additional, useful non‐invasive diagnostic procedure to distinguish between normal skin and skin cancer. [ABSTRACT FROM AUTHOR]

Background: Atopic diseases constitute a major health challenge for industrialized countries, and elevated levels of interleukin 4 (IL-4) frequently characterize these disorders. Previous in vitroanalyses have indicated that IL-4 strongly upregulates the expression of IL-4-sensitive genes in human monocytes. Objective: To explore whether similar expression alterations may contribute to the pathomechanisms of atopic diseases in vivo we carried out a small-scale case-control clinical study (n = 43), in which we quantified the plasma levels of IgE and IL-4 as well as the expression of selected IL-4-sensitive genes in blood leukocytes. Methods: 34 allergic patients suffering from allergic rhinitis (n = 11), atopic eczema (n = 11) and allergic asthma (n = 12) as well as 9 healthy control individuals were recruited. IgE and IL-4 plasma levels were determined by ELISA, and the expression of selected IL-4-sensitive gene products in blood leukocytes was quantified by qRT-PCR. In addition, the fatty acid oxygenase activity of isolated monocytes was measured by RP-HPLC analysis of the arachidonic acid oxygenation products (ex vivo activity assays). Results: We found that plasma levels of IgE and IL-4 were significantly elevated in atopic patients but the degree of elevation was not sufficient to upregulate the expression of the selected IL-4-sensitive genes in circulating leukocytes. Moreover, the arachidonic acid oxygenase activity of blood monocytes was not significantly altered in atopic patients. Conclusion: Our data suggest that the IL-4 plasma levels of atopic patients are not high enough to impact the expression of IL-4-sensitive genes. [ABSTRACT FROM AUTHOR]

Background Psoriasis is a multi-systemic inflammatory disease that results from dysregulation between epidermal keratinocyte homeostasis and both innate and acquired immunity. Epidermal barrier defect has been described in psoriatic lesions. Furthermore an imbalance between pro-oxidative stress and antioxidant defense mechanisms are known in psoriasis patients. Aim The aim of this study was to address the link between disease activity, epidermal barrier and systemic oxidative stress in the course of 311 nm narrow band ultraviolet B (NB-UVB) therapy of psoriasis. The dynamic of systemic oxidative stress parameters as well as local transepidermal water loss (TEWL) and stratum corneum hydration (SCH) was characterized before and after 311 nm NB-UVB therapy on the plaques of psoriasis vulgaris in comparison to untreated non-affected volar forearm sites of the same patients. Material and methods 22 patients with plaque type psoriasis vulgaris and 25 gender- and age-matched healthy controls were enrolled. We assessed the psoriasis area and severity index (PASI) and the dermatology life quality index (DLQI) for monitoring disease activity, severity and self-perceived DLQI impact as patient related outcome parameter. We measured non-invasively TEWL (Tewameter TM 300) and SCH (Corneometer CM 825) and the end product of lipid peroxidation – malondialdehyde (MDA), Reactive oxygen species (ROS), ascorbyl radicals (Asc ) and detoxifying activity of catalase (CAT) were measured in the peripheral blood with spectrophotometric and EPR spectroscopy methods. Results Disease activity improved in all patients compared to baseline witnessed by significant decrease in PASI; (from 14.1 to 10.4; p < 0.0001) and DLQI (from 11.7 to 8.1; p < 0.0001). At baseline TEWL-values were significantly (p < 0.0001) higher on psoriatic plaques (16.8 g/h/m 2 ) in comparison to uninvolved skin (5.3 g/h/m 2 ); with a decrease at both sites after NB-UVB phototherapy. SCH was significantly lower at psoriatic plaque s (4.7AU) compared to uninvolved sskin (42.4AU) and increased after treatment (8.6AU) (p < 0.0001). Interestingly, SCH decrease slightly during therapy at uninvolved skin (40.6AU). ROS and Asc declined during therapy in parallel to a decrease in MDA. A mild decrease in the antioxidative enzyme CAT activity which did not reach the significance was observed. Conclusion The presented data is shows that a clinical improvement of psoriatic plaques under NB-UVB therapy, shown in with a decreased PASI and reflected by an increase in quality of life has beneficial effects on epidermal barrier function, SCH and improvement of systemic oxidative stress parameters (ROS, MDA and Asc ). We assume that the general improvement in the oxidative stress parameters along with epidermal barrier parameters reflects mainly the improvement of disease activity which overwrites the possible negative pro-oxidative effects of the UV treatment. [ABSTRACT FROM AUTHOR]

Raman spectroscopy has proved its capability as an objective, non-invasive tool for the detection of various melanoma and non-melanoma skin cancers ( NMSC) in a number of studies. Most publications are based on a Raman microspectroscopic ex vivo approach. In this in vivo clinical evaluation, we apply Raman spectroscopy using a fibre-coupled probe that allows access to a multitude of affected body sites. The probe design is optimized for epithelial sensitivity, whereby a large part of the detected signal originates from within the epidermal layer's depth down to the basal membrane where early stages of skin cancer develop. Data analysis was performed on measurements of 104 subjects scheduled for excision of lesions suspected of being malignant melanoma ( MM) ( n = 36), basal cell carcinoma ( BCC) ( n = 39) and squamous cell carcinoma ( SCC) ( n = 29). NMSC were discriminated from normal skin with a balanced accuracy of 73% ( BCC) and 85% ( SCC) using partial least squares discriminant analysis ( PLS- DA). Discriminating MM and pigmented nevi ( PN) resulted in a balanced accuracy of 91%. These results lie within the range of comparable in vivo studies and the accuracies achieved by trained dermatologists using dermoscopy. Discrimination proved to be unsuccessful between cancerous lesions and suspicious lesions that had been histopathologically verified as benign by dermoscopy. [ABSTRACT FROM AUTHOR]