Fluctuations in equine cutaneous pH and transepidermal water loss with time of day and ambient conditions.

Cutaneous pH and transepidermal water loss (TEWL) are commonly utilized measures in dermatological research as they provide information concerning barrier function. The importance of dermal health has become more evident in recent years. Accordingly, the aim of this work was to identify natural fluctuations in the biophysical parameters of healthy equine skin. Cutaneous pH and TEWL was collected on nine mares at 6:00 AM, 12:00 PM, and 6:00 PM daily for five days on the nose, withers, girth area, mid-back, and base of tail. Ambient temperature and humidity were measured at each collection. Statistical analysis was completed using SAS On Demand. Tests included repeated measures, ANOVA, and regression analysis. Mean cutaneous pH significantly differed by day (P = 0.0052) and time (P = 0.0073) but was unaffected by anatomical location (P = 0.2841). Interestingly, cutaneous pH had a significant interaction of day and location (P = 0.0004). Mean TEWL measures significantly differed by day (P < 0.0001), time (P < 0.0001), and anatomical location (P = 0.0231). Interaction of day and time had a significant effect on TEWL (P < 0.0001) and also resulted in a three-way interaction of day, time, and location (P = 0.0167). There were no significant associations of pH with temperature and humidity. All measures of TEWL across all locations were significantly correlated with temperature and humidity (P < 0.0001). Cutaneous pH and TEWL measures are affected by environmental conditions which should be considered in future models and work using dermal characteristics of horses.

Models for barrier understanding in health and disease in lab-on-a-chips.

The maintenance of body homeostasis relies heavily on physiological barriers. Dysfunction of these barriers can lead to various pathological processes, including increased exposure to toxic materials and microorganisms. Various methods exist to investigate barrier function in vivo and in vitro. To investigate barrier function in a highly reproducible manner, ethically, and high throughput, researchers have turned to non-animal techniques and micro-scale technologies. In this comprehensive review, the authors summarize the current applications of organ-on-a-chip microfluidic devices in the study of physiological barriers. The review covers the blood-brain barrier, ocular barriers, dermal barrier, respiratory barriers, intestinal, hepatobiliary, and renal/bladder barriers under both healthy and pathological conditions. The article then briefly presents placental/vaginal, and tumour/multi-organ barriers in organ-on-a-chip devices. Finally, the review discusses Computational Fluid Dynamics in microfluidic systems that integrate biological barriers. This article provides a concise yet informative overview of the current state-of-the-art in barrier studies using microfluidic devices.

Characterization and ex vivo evaluation of excised skin samples as substitutes for human dermal barrier in pharmaceutical and dermatological studies.

BACKGROUND: Excised animal and human skins are frequently used in permeability testing in pharmaceutical research. Several factors exist that may have influence on the results. In the current study some of the skin parameters that may affect drug permeability were analysed for human, mouse, rat and pig skin. MATERIALS AND METHODS: Classic biophysical skin parameters were measured (e.g. pH, hydration, permittivity, transepidermal water loss). Physiological characteristics of the skins were also analysed by confocal Raman spectroscopy, scanning electron microscopy and two-photon microscopy. RESULTS: Based on biophysical testing, skin barrier function was damaged in psoriatic mouse skin and in marketed pig skin. Hydration and pH values were similar among the species, but freezing and thawing reduced the water content of the skins and shifted the surface pH to acidic. Aging reduced hydration and permittivity, resulting in impaired barrier function. Mechanical sensitization used in permeability studies resulted in proportional thinning of dead epidermis. DISCUSSION: Results indicate that depending on the scientific question it should be considered whether fresh or frozen tissue is used, and for certain purposes rodent skins are well usable. The structure of the skin tissue (ceramide, cholesterol, keratin, natural moisturizing factor or urea) is similar in rats and mice, but due to the higher skin thickness the lipid distribution is different in porcine skin. Psoriasis led to irregular chemical composition of the skin. CONCLUSION: A comprehensive evaluation of skin samples of four species was performed. The biophysical and microscopic observations should be considered when selecting drug penetration models and experimental conditions.

Development of Skin-On-A-Chip Platforms for Different Utilizations: Factors to Be Considered.

There is increasing interest in miniaturized technologies in diagnostics, therapeutic testing, and biomedicinal fundamental research. The same is true for the dermal studies in topical drug development, dermatological disease pathology testing, and cosmetic science. This review aims to collect the recent scientific literature and knowledge about the application of skin-on-a-chip technology in drug diffusion studies, in pharmacological and toxicological experiments, in wound healing, and in fields of cosmetic science (ageing or repair). The basic mathematical models are also presented in the article to predict physical phenomena, such as fluid movement, drug diffusion, and heat transfer taking place across the dermal layers in the chip using Computational Fluid Dynamics techniques. Soon, it can be envisioned that animal studies might be at least in part replaced with skin-on-a-chip technology leading to more reliable results close to study on humans. The new technology is a cost-effective alternative to traditional methods used in research institutes, university labs, and industry. With this article, the authors would like to call attention to a new investigational family of platforms to refresh the researchers' theranostics and preclinical, experimental toolbox.

Verification of P-Glycoprotein Function at the Dermal Barrier in Diffusion Cells and Dynamic "Skin-On-A-Chip" Microfluidic Device.

The efficacy of transdermal absorption of drugs and the irritation or corrosion potential of topically applied formulations are important areas of investigation in pharmaceutical, military and cosmetic research. The aim of the present experiments is to test the role of P-glycoprotein in dermal drug delivery in various ex vivo and in vitro platforms, including a novel microchip technology developed by Pázmány Péter Catholic University. A further question is whether the freezing of excised skin and age have any influence on P-glycoprotein-mediated dermal drug absorption. Two P-glycoprotein substrate model drugs (quinidine and erythromycin) were investigated via topical administration in diffusion cells, a skin-on-a-chip device and transdermal microdialysis in rat skin. The transdermal absorption of both model drugs was reduced by P-glycoprotein inhibition, and both aging and freezing increased the permeability of the tissues. Based on our findings, it is concluded that the process of freezing leads to reduced function of efflux transporters, and increases the porosity of skin. P-glycoprotein has an absorptive orientation in the skin, and topical inhibitors can modify its action. The defensive role of the skin seems to be diminished in aged individuals, partly due to reduced thickness of the dermis. The novel microfluidic microchip seems to be an appropriate tool to investigate dermal drug delivery.

Skin sparing/skin reducing mastectomy (SSM/SRM) and the concept of oncoplastic breast surgery.

INTRODUCTION: With the better understanding of breast cancer history and biology, improved diagnostic modalities and the shift towards minimally invasive surgeries, indications for prophylactic mastectomy, skin sparing or skin reducing mastectomies (SSM/SRM) with nipple areolar complex (NAC) preservation coupled with immediate breast reconstruction are gaining popularity. The authors share their experience and conception with mastectomy and immediate alloplastic breast reconstruction with the esthetic circumvertical mammoplasty pattern combined with the dermal barrier buttress flap. MATERIAL AND METHODS: The described technique was performed for 28 patients presenting for mastectomy and immediate alloplastic breast reconstruction. With close collaboration between the oncologic and plastic surgeons, mastectomy was performed in all cases with the esthetic circumvertical mammoplasty pattern. To achieve safe excision and optimal reconstruction, the standard incisions could be custom designed to fit oncologic requirements and allow the creation of a dermal barrier flap used as a buttress separating the implant from the suture line. CONCLUSION: The circumvertical mastectomy pattern combined with the dermal barrier buttress flap is a versatile option allowing safe reconstruction regardless of the tumor and necessary skin excision location.