Nitric oxide-induced oxidation of 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid under aerobic conditions: non-enzymatic route to melanin pigments of potential relevance to skin (photo)protection

Diffusible melanin-related metabolites have recently been suggested to subserve a variety of functions that are critical for protection of skin against inflammatory stimuli and oxidative tissue injury. We report here the results of in vitro studies showing that 5,6-dihydroxyindole (DHI) and its 2-carboxylic acid (DHICA) exhibit a marked reactivity toward potentially cytotoxic nitrogen oxides produced by autoxidation of nitric oxide (NO) under physiologically relevant conditions. Exposure of DHI or DHICA to NO in air-equilibrated 0.1 M phosphate buffer, pH 7.4, resulted in a fast, concentration-dependent consumption of the substrates and the concomitant deposition of dark melanin-like pigments. All NO-induced oxidations were completely inhibited in the absence of oxygen. Addition of 10 μM DHI and DHICA completely prevented the oxidation of 10 μM α-tocopherol in 0.1 M phosphate buffer, pH 7.4 in the presence of 300 μM NO. Overall, these results shed light on novel oxidative pathways of melanin-related metabolites of possible relevance to the mechanisms of skin hyperpigmentation under oxidative stress conditions.     

Skin surface markers for stereotactic body radiation therapy of sternal metastasis

Stereotactic body radiation therapy is an effective and safe treatment modality for bone metastasis which allows clinicians to accurately target lesions to high doses while minimizing dose to organs at risk. The commercially available CyberKnife^® Xsight? Spine Tracking System (Accuray, Inc., Sunnyvale, CA) tracks static skeletal structures and eliminates the need for implanted fiducial markers (FMs). However, the Xsight? Spine Tracking system is not appropriate for bone metastases outside the spine, which are moving due to respiration and ,typically, FMs have to be implanted close to the lesion. These FMs will be used to track the dynamic target. For targets close to the surface, non-invasive fixation of the FMs to the patient's skin could be an option.     

Ultrastructure and wear patterns of the ventral epidermis of four snake species (Squamata,Serpentes)

Snakes are limbless tetrapods highly specialized for sliding locomotion. This locomotion leads to the skin being exposed to friction loads, especially on the ventral body side, which leads to wear. It is presumed that snakes therefore have specific optimizations for minimizing abrasion. Scales from snakes with habitat, locomotor and/or behavior specializations have specific gradients in material properties that may be due to different epidermal architecture. To approach this issue we examined the skin of Lampropeltis getula californiae (terrestrial), Epicrates cenchria cenchria (generalist), Morelia viridis (arboreal), and Gongylophis colubrinus (burrowing) with a focus on (i) the ultrastructure of the ventral epidermis and (ii) the qualitative abrasion pattern of the ventral scales. Scanning and transmission electron microscopy revealed variations in the structure, thickness, layering, and material composition of the epidermis between the species. Furthermore, SEM and white light interferometer images of the scale surface showed that the abrasion patterns differed, even when the snakes were reared on the same substrate. These data support the idea that (i) a specific gradient in material properties may be due to a variation in epidermis architecture (thickness/ultrastructure) and (ii) this variation may be an optimization of material properties for specific ways of life.     

Participation of interferons in psoriatic inflammation

Interferons are multifunctional cytokines not expressed in the skin under normal physiological conditions. However, they are overexpressed in serum and skin lesions of patients with psoriasis and play an important role in the pathogenesis of the disease. Interferons act directly on skin resident cells and recruit and modulate inflammatory cells, thereby exacerbating psoriatic inflammation. They upregulate the expression of relevant cytokines and chemokines, facilitate excessive proliferation of keratinocytes, and enhance the formation of poorly differentiated dermal microvessels. In this review, we summarized the pathogenic effect of interferons on psoriasis and also discussed the therapeutic strategies targeting interferons.     

Identification of compounds in red wine that effectively upregulate aquaporin-3 as a potential mechanism of enhancement of skin moisturizing

In a previous clinical study, the moisture content in the stratum corneum of healthy Japanese women who consumed a beverage rich in oligomeric proanthocyanidins (OPCs) made from red wine extract was found to be higher than that in the control group. This finding suggested that OPCs can increase skin moisture content. In this study, we determined the expression level of aquaporin-3 (AQP3) in keratinocytes to elucidate the mechanism by which compounds in red wine grape increase moisture content in stratum corneum. Through in vitro studies, we confirmed that normal human epidermal keratinocytes (NHEK) incubated with red wine induced AQP3 expression. Furthermore, the supplementation of red wine fractions enriched in OPC was shown to increase AQP3 expression. Besides, the component of OPC-rich fractions that upregulated AQP3 expression was found to be a gallic acid (GA)-binding flavan-3-ol, particularly oligomeric compounds. We found that GA-binding OPC were able to upregulate AQP3 expression and that these compounds were enriched in red wine. Our findings might suggest that the mechanism of enhancement of moisture content in stratum corneum by red wine might be via the upregulation of AQP3 expression in the epidermal keratinocytes.     

Peripheral skin temperature effects on muscle oxygen levels

In both hot and cold environments, tissue oxygen saturation levels may affect muscle performance. Using near-infrared spectroscopy, muscle oxygen saturation (StO2) and total hemoglobin levels were measured during exercise. Lowering skin temperature caused a greater StO2 and total hemoglobin decrease by 16% and 15.9%, respectively, compared to controls. Increasing skin temperature resulted in a smaller decrease in both StO2 and total hemoglobin by 12.2% and 8.2%, respectively, compared to controls. These data indicate that warming the skin will cause less of decrease in StO2 and total hemoglobin, while cooling the skin has the opposite effect.     

Eicosanoids in skin inflammation

Eicosanoids play an integral part in homeostatic mechanisms related to skin health and structural integrity. They also mediate inflammatory events developed in response to environmental factors, such as exposure to ultraviolet radiation, and inflammatory and allergic disorders, including psoriasis and atopic dermatitis. This review article discusses biochemical aspects related to cutaneous eicosanoid metabolism, the contribution of these potent autacoids to skin inflammation and related conditions, and considers the importance of nutritional supplementation with bioactives such as omega-3 and omega-6 polyunsaturated fatty acids and plant-derived antioxidants as means of addressing skin health issues.     

Thermoregulatory anatomy of pronghorn (Antilocapra americana)

We have found that pronghorn (Antilocapra americana) use external heat exchange with the environment and internal heat exchange between the carotid artery rete and cavernous venous sinus blood to regulate body temperature. Now we have investigated the relationship between the histological structure of the skin, cephalic veins, and carotid rete–cavernous sinus system and the physiological mechanisms pronghorn use, and whether their thermoregulatory anatomy has adaptive advantages. We harvested tissue samples of skin, three veins (i.e., angularis oculi vein, dorsal nasal vein, and facial vein), and the carotid rete–cavernous sinus system from four pronghorn, two culled in summer and two in winter, and examined each histologically. The three veins had the typical structure of veins with large lumina and thin walls. The carotid rete consisted of small (0.1–0.5 mm) arterioles with a density of ~10/mm², intertwined with veins (~2/mm²), enclosed within the cavernous sinus; a structure ideal for heat exchange. We concluded that the main function of the dorsal nasal and facial veins is to return cold blood to the body to effect whole body cooling. The cavernous sinus is supplied with warm blood by the palatine veins in winter and cold blood by the deep facial veins in summer, an arrangement different to that in other ungulates, such as sheep, in which the angularis oculi vein supplies the cavernous sinus. Pronghorn skin is richly supplied with blood vessels that facilitate convective heat loss in summer. In winter, the number of coarse and fine hairs per square millimeter increases more than in European deer to form a thick pelage that minimizes heat loss. In summer, the pelage is shed because hair follicles involute. Unlike in other ungulates, pronghorn skin has little adipose tissue. The number of apocrine glands increases in winter rather than in summer. We concluded that the glands have a reproductive/social function rather than a thermoregulatory one. In summary, our study shows that the thermoregulatory anatomy is consistent with our physiological data and has adaptive advantages that help explain the survival of pronghorn in an arid habitat characterized by extreme temperature variation and sparse vegetation.