Nanodelivery Strategies for Skin Diseases with Barrier Impairment: Focusing on Ceramides and Glucocorticoids

The human epidermis has a characteristic lipidic composition in the stratum corneum, where ceramides play a crucial role in the skin barrier homeostasis and in water-holding capacity. Several skin diseases, such as atopic dermatitis and psoriasis, exhibit a dysfunction in the lipid barrier with altered ceramide levels and increased loss of transepidermal water. Glucocorticoids are normally employed in the therapeutical management of these pathologies. However, they have shown a poor safety profile and reduced treatment efficiency. The main objective of this review is to, within the framework of the limitations of the currently available therapeutical approaches, establish the relevance of nanocarriers as a safe and efficient delivery strategy for glucocorticoids and ceramides in the topical treatment of skin disorders with barrier impairment.

Canine Epidermal Keratinocytes (CPEK) Grown in Monolayer Are Not Representative of Normal Canine Keratinocytes for Permeability Studies: Pilot Studies

Canine progenitor epidermal keratinocytes (CPEK) are used as canine keratinocyte cell line. Their suitability for skin barrier studies is unknown. Measurement of transepithelial electric resistance (TEER) evaluates epithelial permeability. We compared TEER and tight junction (TJ) expression in CPEKs and normal keratinocytes (NK) harvested from biopsies of normal dogs. CPEKs and NK were grown until confluence (D0) and for 13 additional days. Slides were fixed on D0 and stained with ZO-1 and claudin-1 antibodies. Five images/antibody were taken, randomized and evaluated blindly by three investigators for intensity, staining location, granularity, and continuousness. Cell size and variability were evaluated. TEER increased overtime to 2000 Ohms/cm in NK, while remained around 100–150 Ohms/cm in CPEK. ANOVA showed significant effect of time (p < 0.0001), group (p < 0.0001) and group x time interaction (p < 0.0001) for TEER. Size of CPEKs was significantly (p < 0.0001) smaller and less variable (p = 0.0078) than NK. Intensity of claudin-1 staining was greater in CPEKs (p < 0.0001) while granularity was less in CPEKs (p = 0.0012). For ZO-1, cytoplasmic staining was greater in CPEK (p < 0.0001) while membrane continuousness of staining was greater in NK (p = 0.0002). We conclude that CPEKs grown in monolayer are not representative of NK for permeability studies.

Eradication of Ventricular Assist Device Driveline Infection in Paediatric Patients with Taurolidine

Ventricular assist devices (VADs) are used to provide mechanical circulatory support to patients with end-stage heart failure. The driveline connecting the external power source to the pump(s) of the intra-corporal VAD breaches the protective skin barrier and provides a track for microbes to invade the interior of the patient’s body. Driveline infection constitutes a major and potentially fatal vulnerability of VAD therapy. Driveline infection cannot traditionally be salvaged and requires the extraction of the entire VAD system. We report here the successful eradication of a VAD driveline infection with a taurolidine-containing antimicrobial solution used for preventing the infection of cardiac implantable electronic devices. If replicated in more cases, the novel treatment concept described here may provide a valuable alternative management strategy of salvage rather than explantation for VAD driveline infection.

Impact of Water Exposure and Temperature Changes on Skin Barrier Function

The frequency of hand hygiene has increased due to the COVID-19 pandemic, but there is little evidence regarding the impact of water exposure and temperature on skin. The aim of this study is to evaluate the effect of water exposure and temperature on skin barrier function in healthy individuals. A prospective observational study was conducted. Temperature, pH, transepidermal water loss (TEWL), erythema and stratum corneum hydration (SCH) were measured objectively before and after hot- and cold-water exposure and TempTest® (Microcaya TempTest, Bilbao, Spain) contact. Fifty healthy volunteers were enrolled. Hot-water exposure increased TEWL (25.75 vs. 58.58 g·h−1·m−2), pH (6.33 vs. 6.65) and erythema (249.45 vs. 286.34 AU). Cold-water immersion increased TEWL (25.75 vs. 34.96 g·h−1·m−2) and pH (6.33 vs. 6.62). TEWL (7.99 vs. 9.98 g·h−1·m−2) and erythema (209.07 vs. 227.79 AU) increased after being in contact with the hot region (44 °C) of the TempTest. No significant differences were found after contact with the cold region (4 °C) of the TempTest. In conclusion, long and continuous water exposure damages skin barrier function, with hot water being even more harmful. It would be advisable to use cold or lukewarm water for handwashing and avoid hot water. Knowing the proper temperature for hand washing might be an important measure to prevent flares in patients with previous inflammatory skin diseases on their hands.

Impact of Exposome Factors on Epidermal Barrier Function in Patients with Obstructive Sleep Apnea Syndrome

Exposome factors, such as sleep deprivation and diet, could affect skin barrier function. The objectives of this study are to compare skin barrier function between patients with Obstructive Sleep Apnea Syndrome (OSAS) and healthy individuals, and to evaluate the effect of other exposome factors on skin. A cross-sectional study was conducted. Patients with OSAS and healthy volunteers matched by age and sex were included. OSAS severity was assessed by the Apnea-Hypopnea Index (AHI). Validated questionnaires were used to assess diet, anxiety, depression, and psychological stress. Skin barrier function parameters including temperature, erythema, melanin, pH, transepidermal water loss (TEWL), and stratum corneum hydration (SCH) were measured on the volar forearm. A total of 86 participants were included, 56 patients with OSAS and 30 healthy volunteers. TEWL was higher in OSAS patients than in healthy individuals (8.01 vs. 8.68 g·m−2·h−1). Regarding disease severity, severe patients had higher TEWL values (9.31 vs. 8.46 vs. 7.08 g·m−2·h−1) compared to moderate and mild patients. Patients with OSAS had significantly lower sleep quality (11.89 vs. 6.47 Pittsburgh Sleep Quality Index score; p < 0.001), poor adherence to the Mediterranean Diet (8.46 vs. 9.77; p = 0.005), and significantly higher anxiety and depression levels than healthy individuals. In conclusion, patients with OSAS may have skin barrier impairment, reflected in higher TEWL values. These patients also have higher levels of anxiety, depression, stress, and a lower adherence to a Mediterranean Diet, all exposome factors that might impact on skin barrier function.

Epicutaneous sensitization. what do we know?

Background. According to the currently existing hypothesis, epicutaneous sensitization is one of the leading mechanisms in the development of food allergy.The aim of this review was to analyze immune mechanisms in epicutaneous sensitization and the role of skin barrier impairment.We performed a literature search using PubMed, UpToDate, Web of Science, and Scopus databases by the key words: epicutaneous sensitization, atopic dermatitis, skin barrier impairment, food allergy. Articles were to be in open access and present the most relevant information on the topic. Studies were selected by the largest sample size and the highest citation index. Once publications were identified, they were reviewed by all the authors to select the studies that specifically addressed the theme of the review. A total of 101 publications from 1998–2000 were included in the study.This review article discusses the data of experimental studies, sets out modern ideas about the hypothesis of a double exposure to an allergen, and presents research data proving the clinical significance of epicutaneous sensitization in relation to food allergy. Knowledge about the mechanisms of epicutaneous sensitization development is necessary to elaborate strategies for prevention of food allergy. One of the modern trends in prevention is the use of emollients, which are supposed to restore the skin response. However, studies on preventive intake of emollients do not present a similar viewpoint.There is not enough evidence for or against the mechanism of epicutaneous sensitization as an indispensable condition for the formation of food allergies. Further research in this area is required.