[CYP3A inhibitors as a pharmacokinetic enhancer: pros and cons of drug interactions].

Certain drugs inherently have unfavourable pharmacokinetic properties; for example, they are poorly absorbed or broken down too quickly in the liver. In some cases, the addition of a pharmacokinetic excipient, thus deliberately causing an interaction, may offer a solution. To date, this concept has been most widely applied in HIV treatment where addition of the CYP3A inhibitors ritonavir and cobicistat greatly increases plasma levels of other HIV medications.

Carboxamide Derivatives Are Potential Therapeutic AHR Ligands for Restoring IL-4 Mediated Repression of Epidermal Differentiation Proteins.

Atopic dermatitis (AD) is a common T-helper 2 (Th2) lymphocyte-mediated chronic inflammatory skin disease characterized by disturbed epidermal differentiation (e.g., () expression) and diminished skin barrier function.

Identification of Keratinocyte Mitogens: Implications for Hyperproliferation in Psoriasis and Atopic Dermatitis.

Psoriasis and atopic dermatitis are chronic inflammatory skin diseases characterized by keratinocyte (KC) hyperproliferation and epidermal acanthosis (hyperplasia). The milieu of disease-associated cytokines and soluble factors is considered a mitogenic factor; however, pinpointing the exact mitogens in this complex microenvironment is challenging. We employed organotypic human epidermal equivalents, faithfully mimicking native epidermal proliferation and stratification, to evaluate the proliferative effects of a broad panel of (literature-based) potential mitogens.

Perfusion measured by laser speckle contrast imaging as a predictor for expansion of psoriasis lesions.

Background: Skin microvasculature changes are crucial in psoriasis development and correlate with perfusion. The noninvasive Handheld Perfusion Imager (HAPI) examines microvascular skin perfusion in large body areas using laser speckle contrast imaging (LSCI).

Objectives: To (i) assess whether increased perilesional perfusion and perfusion inhomogeneity are predictors for expansion of psoriasis lesions and (ii) assess feasibility of the HAPI system in a mounted modality.

Vesicular hand eczema transcriptome analysis provides insights into its pathophysiology.

Hand eczema is a common inflammatory skin condition of the hands whose pathogenesis is largely unknown. More insight and knowledge of the disease on a more fundamental level might lead to a better understanding of the biological processes involved, which could provide possible new treatment strategies. We aimed to profile the transcriptome of lesional palmar epidermal skin of patients suffering from vesicular hand eczema using RNA-sequencing.

Skin Surface Protein Detection by Transdermal Analysis Patches in Pediatric Psoriasis.

Introduction: Transdermal analysis patches (TAPs) noninvasively measure soluble proteins in the stratum corneum. Ultimately, such local protein profiles could benefit the search for biomarkers to improve personalized treatment in psoriasis. This study aimed to explore the patient friendliness and protein detection by TAP in pediatric psoriasis in daily clinical practice.

Immune responses to azacytidine in animal models of inflammatory disorders: a systematic review.

Inflammatory disorders like diabetes, systemic lupus erythematodes, inflammatory lung diseases, rheumatoid arthritis and multiple sclerosis, but also rejection of transplanted organs and GvHD, form a major burden of disease. Current classes of immune suppressive drugs to treat these disorders are never curative and side effects are common. Therefore there is a need for new drugs with improved and more targeted modes of action.

Biopsy outperforms reflectance confocal microscopy in diagnosing and subtyping basal cell carcinoma: results and experiences from a randomized controlled multicentre trial.

Background: Reflectance confocal microscopy (RCM) is a noninvasive method for skin assessment, allowing entire lesion evaluation up to the papillary dermis. RCM is a potentially attractive alternative to punch biopsy (PB) in basal cell carcinoma (BCC).

Objectives: To determine the diagnostic accuracy of RCM vs.

Value of GPSkin for the measurement of skin barrier impairment and for monitoring of rosacea treatment in daily practice.

Background: Stratum corneum hydration (SCH) and transepidermal water loss (TEWL) provide useful information about skin barrier function. This study aimed to determine the value of GPSkin Pro, a new handheld device determining both SCH and TEWL, to measure skin barrier impairment and to monitor barrier function in rosacea in daily practice.

Materials And Methods: Two pilots were performed.

Evaluation of a simple image-based tool to quantify facial erythema in rosacea during treatment.

Background: Facial erythema is a common symptom in rosacea. To overcome subjectivity in scoring erythema severity, objective redness quantification is desirable. This study evaluated an image-based erythema quantification tool to monitor facial erythema in rosacea patients during treatment and compared these values to clinical scores.

Successful Regulatory T Cell-Based Therapy Relies on Inhibition of T Cell Effector Function and Enrichment of FOXP3+ Cells in a Humanized Mouse Model of Skin Inflammation.

Background: Recent clinical trials using regulatory T cells (Treg) support the therapeutic potential of Treg-based therapy in transplantation and autoinflammatory diseases. Despite these clinical successes, the effect of Treg on inflamed tissues, as well as their impact on immune effector function , is poorly understood. Therefore, we here evaluated the effect of human Treg injection on cutaneous inflammatory processes using a humanized mouse model of human skin inflammation (huPBL-SCID-huSkin).

Value of reflectance confocal microscopy for the monitoring of rosacea during treatment with topical ivermectin.

Background: Reflectance confocal microscopy (RCM) enables noninvasive mite detection in rosacea. Objective scoring of rosacea severity is currently lacking.

Objectives: To determine the value of RCM for monitoring , inflammation and vascular parameters in rosacea during treatment.

Reliability and Responsiveness of the Observable Movement Quality Scale for Children with Mild to Moderate Motor Impairments.

Aim: The Observable Movement Quality (OMQ) scale measures generic movement quality and is used alongside standardized age-adequate motor performance tests. The scale consists of 15 items, each focusing on a different aspect; together, the entire construct of movement quality is assessed. This study aimed to determine interrater and intrarater reliability, and responsiveness of the OMQ scale.

Skin Barrier Impairment due to the Occlusive Effect of Firefighter Clothing.

At fire scenes, firefighters are exposed to potentially harmful substances. Besides inhalation of these products, also skin contamination and the risk of dermal absorption is getting more attention. In this perspective, skin barrier impairment due to the occlusive effect of firefighter clothes could enhance the risk of penetration of hazardous substances.

Noninvasive objective skin measurement methods for rosacea assessment: a systematic review.

Background: Rosacea assessment and therapy monitoring can be challenging to standardize, as most clinical evaluation systems are prone to interobserver variability and not always validated. Therefore, objective, reliable and preferably noninvasive measurement tools are needed.

Objectives: To give insight into available noninvasive imaging techniques and biophysical methods in rosacea by performing a systematic review.

Assessment of reflectance confocal microscopy for non-invasive selection of optimal ovarian cortex fragments for autotransplantation.

Research Question: Can reflectance confocal microscopy (RCM) be used to determine follicle density in human ovarian cortex fragments that are intended for fertility restoration?

Design: RCM was used on living cortex tissue fragments derived from five bovine ovaries and 13 human ovaries. All tissue fragments were cryopreserved and thawed before RCM analysis. Follicle numbers and distribution were determined by RCM and histology.

Development of a Novel Approach to Studying Corneodesmosomes and Stratum Corneum Adhesion: Extending Knowledge on the Pathophysiology of Sensitive Skin.

Background/aims: Aberrant skin barrier and intercorneocyte adhesion are potential contributors to the pathomechanism of sensitive skin (SS). Here we aimed to develop a novel and easy-to-apply method to analyze corneodesmosomes and to interrogate potential differences between corneocytes of subjects with SS and non-SS (NSS).

Methods: Corneocytes of the volar forearm and upper outer quadrant of the left buttock of SS (n = 10) and NSS (n = 8) subjects were extracted as a function of depth using adhesive tape and stained with anti-desmoglein 1 (DSG1) antibody.

Anatomical site variation of water content in human skin measured by the Epsilon: A pilot study.

Background: This pilot study aimed to investigate the anatomical site variation of water content of the stratum corneum (SC) on the body by measuring skin capacitance with the Epsilon, a new generation corneometer with multiple sensors. Secondly, values of the Epsilon were compared to values measured by conventional single sensor corneometers.

Methods: The hydration status of SC was measured in 15 healthy Caucasian volunteers with the Epsilon at five body sites (cheek, lower forearm, mid-calf, lower back and abdomen).

Deficiency of the human cysteine protease inhibitor cystatin M/E causes hypotrichosis and dry skin.

Purpose: We aimed to assess the biological and clinical significance of the human cysteine protease inhibitor cystatin M/E, encoded by the CTS6 gene, in diseases of human hair and skin.

Methods: Exome and Sanger sequencing was performed to reveal the genetic cause in two related patients with hypotrichosis. Immunohistochemical, biophysical, and biochemical measurements were performed on patient skin and 3D-reconstructed skin from patient-derived keratinocytes.

The value of (video)dermoscopy in the diagnosis and monitoring of common inflammatory skin diseases: a systematic review.

Clinical diagnosis of inflammatory skin disorders (ISD), including hair and nail disorders, is not always straightforward. Not uncommonly, a punch biopsy may be required. Dermoscopy and videodermoscopy (VD) are non-invasive techniques that are used for in vivo examination of the skin, hair, and nails.

The effect of adalimumab on the vasculature in psoriatic skin lesions.

Background: Vascular proliferation is considered an important feature in psoriasis. Early psoriatic changes are characterized by vascular network expansion; healing of the lesions ultimately results in a decreasing size of the vascular network. Currently, the response of the vasculature in psoriatic lesions during treatment of adalimumab is still obscure.

Noninvasive analysis and minimally invasive in vivo experimental challenges of the skin barrier.

In this review, we aim to give a concise and selective overview of noninvasive biophysical analysis techniques for skin barrier analysis (transepidermal water loss, electrical methods, confocal Raman microspectroscopy, sebumeter, reflectance spectrophotometry, tristimulus colorimetry, diffuse reflectance spectroscopy and reflectance confocal microscopy), including advantages and limitations. Rather than giving an exhaustive description of the many techniques currently available, we show the usefulness of a representative selection of techniques in the functional and morphological evaluation of the skin barrier. Furthermore, we introduce human minimally invasive skin challenging models as a means to study the mechanisms regulating skin homoeostasis and disease and subsequently show how biophysical analysis techniques can be combined with these in vivo skin challenging models in the functional and morphological evaluation of the skin barrier in healthy human skin.

Intradermal injection of low dose human regulatory T cells inhibits skin inflammation in a humanized mouse model.

Recent regulatory T cell (Treg) based clinical trials support their therapeutic potential in transplantation and auto-inflammatory diseases. However, large numbers of Treg are needed to accomplish therapeutic efficacy. Local injection at the site of inflammation (targeted delivery) may lower the numbers needed for therapy.