Raja K. Sivamani

Coefficient of friction: tribological studies in man – an overview

Background/purpose: Compared to other studies of skin, relatively few studies have focused on the friction of skin. This work reviews existing skin friction, emphasizing test apparatuses and parameters that have added to information regarding the friction coefficient. This review also outlines what factors are important to consider in future friction studies.

Friction coefficient of skin in real‐time

Background/purpose: Friction studies are useful in quantitatively investigating the skin surface. Previous studies utilized different apparatuses and materials for these investigations but there was no real‐time test parameter control or monitoring. Our studies incorporated the commercially available UMT Series Micro‐Tribometer, a tribology instrument that permits real‐time monitoring and calculation of the important parameters in friction studies, increasing the accuracy over previous tribology and friction measurement devices used on skin.

Microneedles and transdermal applications

With the limitations of oral drug delivery and the pain and needle phobias associated with traditional injections, drug delivery research has focused on the transdermal delivery route. A formidable barrier to transdermal drug delivery is the stratum corneum, the superficial layer of the skin. In the last 10 years, microneedles were proposed as a mechanical tool to pierce through the stratum corneum, in order to create drug delivery channels without stimulating underlying pain nerves. Since then, the field of microneedles has rapidly evolved to spawn a plethora of potential transdermal applications. In this review, the authors provide an overview of the progress in microneedle research and design, and the advancements that have been made in employing this technology for transdermal applications.

Stress-Mediated Increases in Systemic and Local Epinephrine Impair Skin Wound Healing: Potential New Indication for Beta Blockers

Background Stress, both acute and chronic, can impair cutaneous wound repair, which has previously been mechanistically ascribed to stress-induced elevations of cortisol. Here we aimed to examine an alternate explanation that the stress-induced hormone epinephrine directly impairs keratinocyte motility and wound re-epithelialization. Burn wounds are examined as a prototype of a high-stress, high-epinephrine, wound environment. Because keratinocytes express the β2-adrenergic receptor (β2AR), another study objective was to determine whether β2AR antagonists could block epinephrine effects on healing and improve wound repair. Methods and Findings Migratory rates of normal human keratinocytes exposed to physiologically relevant levels of epinephrine were measured. To determine the role of the receptor, keratinocytes derived from animals in which the β2AR had been genetically deleted were similarly examined. The rate of healing of burn wounds generated in excised human skin in high and low epinephrine environments was measured. We utilized an in vivo burn wound model in animals with implanted pumps to deliver β2AR active drugs to study how these alter healing in vivo. Immunocytochemistry and immunoblotting were used to examine the up-regulation of catecholamine synthetic enzymes in burned tissue, and immunoassay for epinephrine determined the levels of this catecholamine in affected tissue and in the circulation. When epinephrine levels in the culture medium are elevated to the range found in burn-stressed animals, the migratory rate of both cultured human and murine keratinocytes is impaired (reduced by 76%, 95% confidence interval [CI] 56%–95% in humans, p < 0.001, and by 36%, 95% CI 24%–49% in mice, p = 0.001), and wound re-epithelialization in explanted burned human skin is delayed (by 23%, 95% CI 10%–36%, p = 0.001), as compared to cells or tissues incubated in medium without added epinephrine. This impairment is reversed by β2AR antagonists, is absent in murine keratinocytes that are genetically depleted of the β2AR, and is reproduced by incubation of keratinocytes with other β2AR-specific agonists. Activation of the β2AR in cultured keratinocytes signals the down-regulation of the AKT pathway, accompanied by a stabilization of the actin cytoskeleton and an increase in focal adhesion formation, resulting in a nonmigratory phenotype. Burn wound injury in excised human skin also rapidly up-regulates the intra-epithelial expression of the epinephrine synthesizing enzyme phenylethanolamine-N-methyltransferase, and tissue levels of epinephrine rise dramatically (15-fold) in the burn wounded tissue (values of epinephrine expressed as pg/ug protein ± standard error of the mean: unburned control, 0.6 ± 0.36; immediately postburn, 9.6 ± 1.58; 2 h postburn, 3.1 ± 1.08; 24 h post-burn, 6.7 ± 0.94). Finally, using an animal burn wound model (20% body surface in mice), we found that systemic treatment with βAR antagonists results in a significant increase (44%, 95% CI 27%–61%, p < 0.00000001) in the rate of burn wound re-epithelialization. Conclusions This work demonstrates an alternate pathway by which stress can impair healing: by stress-induced elevation of epinephrine levels resulting in activation of the keratinocyte β2AR and the impairment of cell motility and wound re-epithelialization. Furthermore, since the burn wound locally generates epinephrine in response to wounding, epinephrine levels are locally, as well as systemically, elevated, and wound healing is impacted by these dual mechanisms. Treatment with beta adrenergic antagonists significantly improves the rate of burn wound re-epithelialization. This work suggests that specific β2AR antagonists may be apt, near-term translational therapeutic targets for enhancing burn wound healing, and may provide a novel, low-cost, safe approach to improving skin wound repair in the stressed individual.

Tribometrology of skin

The quantitative assessment of both skin health and skin care products is suggested based on skin tribological properties. Simultaneous multi-sensor measurements of both coefficient of friction and contact electrical impedance allow for fast and quantitative evaluation of skin conditions such as dryness and moisturization, and early diagnosis of skin diseases or of the deterioration in skin functions at a stage that may not be easily discernable visibly. It may be instrumental in developing and testing skin cosmetics and medicine.

Antioxidant Therapies for Wound Healing: A Clinical Guide to Currently Commercially Available Products

Many facets of wound healing under redox control require a delicate balance between oxidative stress and antioxidants. While the normal physiology of wound healing depends on low levels of reactive oxygen species and oxidative stress, an overexposure to oxidative stress leads to impaired wound healing. Antioxidants are postulated to help control wound oxidative stress and thereby accelerate wound healing. Many antioxidants are available over the counter or by prescription, but only one, Medihoney®, has been specifically FDA approved for wound healing. Here we review the existing evidence for the use of antioxidants for wound healing, with a review of the pertinent animal and clinical studies. Natural products and naturally derived antioxidants are becoming more popular, and we specifically review the evidence for the use of naturally derived antioxidants in wound healing. Antioxidant therapy for wound healing is promising, but only few animal studies and even fewer clinical studies are available. Because only few products have undergone FDA approval, the consumer is advised to scrutinize them for purity and contaminants prior to use, and this may require direct contact with the companies that sell them. As a field of science, the use of antioxidants for wound healing is in its infancy, and future studies will better elucidate the role of antioxidants in wound healing.

Tribological testing of skin products: gender, age, and ethnicity on the volar forearm

Background/purpose: Few studies have focused on the simultaneous measurement of the friction and electrical properties of skin. This work investigates the feasibility of using these measurements to differentiate between the effects of chemicals commonly applied to the skin. In addition, this study also compares the condition of the skin and its response to application of chemicals across gender, ethnicity, and age at the volar forearm.

Biologic Therapies in the Treatment of Psoriasis: A Comprehensive Evidence-Based Basic Science and Clinical Review and a Practical Guide to Tuberculosis Monitoring

The treatment of psoriasis has undergone a revolution with the advent of biologic therapies including infliximab, etanercept, adalimumab, efalizumab, golimumab, certolizumab, alefacept, secukinumab, abatacept, and ustekinumab. These medications are designed to target specific components of the immune system and are a major technological advancement over traditional immunosuppressive medications. Herein, we present a comprehensive, unbiased comparison of these medications focusing on their differences. For example, TNF antagonists can differ in the way they are dissolved and administered, the effector molecules they can bind, serum peak and trough levels, the types of intracellular signals they can induce, the in vivo complexes that they can form, their protein structure, and their incidence and timing of rare adverse events, among other things. A critical review of the clinical studies that have tested the efficacy of these molecules is also presented including head-to-head comparison trials. The safety of biologics in terms of their long-term adverse events is discussed, as is their use in different types of psoriasis and in different patient populations. Finally, all anti-TNF agents have been associated with a variety of serious and “routine” opportunistic infections, particularly tuberculosis. For this reason, anti-tuberculosis testing both prior to the initiation of a biologic therapy and annually during treatment is pertinent. The uses and limitations of both the tuberculin skin test (TST) and QuantiFeron®-TB Gold (QFT) are discussed, as is the care of patients who present with latent tuberculosis infection prior to the initiation of biologic therapy. Recommendations for tuberculosis monitoring are provided.

The use of botanically derived agents for hyperpigmentation: A systematic review

BACKGROUND Hyperpigmentation disorders are common among those seeking care from dermatologists and primary care physicians. The cosmeceutical and natural product industries are rapidly growing and many botanical agents are purported to improve hyperpigmentation disorders. OBJECTIVE We sought to review clinical evidence for the use of botanical agents in the treatment of hyperpigmentation. METHODS We searched MEDLINE and Embase databases and a total of 26 articles met inclusion criteria. Study methodology was analyzed and the reproducibility of the studies was graded. RESULTS Several botanical agents appear promising as treatment options but few studies were methodologically rigorous. Several plant extract and phytochemicals effectively lighten signs of epidermal melasma and hyperpigmentation induced by ultraviolet radiation exposure. Results were mixed for treatment of solar lentigines or dermal hyperpigmentation. LIMITATIONS There were few rigorously designed studies; future research will be critical to further ascertain the discussed results. CONCLUSIONS The subtype of hyperpigmentation is important for treatment prognosis, with dermal hyperpigmentation less responsive to treatment. Botanical extracts may play an integrative role in the treatment of hyperpigmentation and further studies that integrate them with standard therapies are needed. Side effects, including worsened hyperpigmentation, need to be discussed when considering these therapies.

BIOLOGICAL THERAPY OF PSORIASIS

The treatment of psoriasis has undergone a revolution with the advent of biologic therapies, including infliximab, etanercept, adalimumab, efalizumab, and alefacept. These medications are designed to target specific components of the immune system and are a major technological advancement over traditional immunosuppressive medications. These usually being well tolerated are being found useful in a growing number of immune-mediated diseases, psoriasis being just one example. The newest biologic, ustekinumab, is directed against the p40 subunit of the IL-12 and IL-23 cytokines. It has provided a new avenue of therapy for an array of T-cell-mediated diseases. Biologics are generally safe; however, there has been concern over the risk of lymphoma with use of these agents. All anti-TNF-α agents have been associated with a variety of serious and “routine” opportunistic infections.