Effect of seasonal and geographical differences on skin and effect of treatment with an osmoprotectant: Sorbitol.

Human skin maintains an optimal permeability barrier function in a terrestrial environment that varies considerably in humidity. Cells cultured under hyperosmotic stress accumulate osmolytes including sorbitol. Epidermal keratinocytes experience similar high osmolality under dry environmental conditions because of increased transepidermal water loss (TEWL) and concomitant drying of the skin. This study was designed to determine if epidermal keratinocytes, in vitro, could be protected from high osmotic stress, with the exogenous addition of sorbitol. In addition, we evaluated the effect of a formulation containing topical sorbitol on skin barrier and moisturization of subjects living in arid and humid regions in summer as well as in winter. Results from in vitro experiments showed that 50 mM sorbitol protected epidermal keratinocytes from osmotic toxicity induced by sodium chloride. Clinical studies indicated that skin chronically exposed to hot, dry environment appeared to exhibit stronger skin barrier and a lower baseline TEWL. In addition, skin barrier was stronger in summer than in winter. Sorbitol exhibited significant improvement in both barrier repair and moisturization, especially in individuals subjected to arid environmental conditions.

Enzymatically generated hydrogen peroxide reduces the number of acne lesions in acne vulgaris.

A major component to the etiology of acne is the growth and invasion by Propionibacterium acnes. Hydrogen peroxide is an excellent antimicrobial agent but is unstable in most formulations. We have developed a hydrogen peroxide generation system using the enzyme glucose oxidase and glucose. This system is stable in a simple formulation and nonirritating. In a short-term clinical study (4 days), this formulation was effective in reducing the individual lesion size and total number of inflammatory acne lesions. There was a 68% reduction in acne-induced inflammation and 61% reduction in acne size within 4 days of treatment. A long-term clinical study (6 weeks in use) displayed 56% reduction in total number of inflamed lesions and a 45% reduction in noninflamed lesions after 6 weeks. This suggests that topical enzymatically generated hydrogen peroxide may help alleviate acne.

UV protection afforded by gel-trapped TiO2 particles.

We have developed a technology to incorporate micronized titanium dioxide (TiO(2)), together with antioxidants, in particles of a UV-visible transparent polymer gel. These particles are coated with silica to avoid clustering and the size of the micronized TiO(2) reduces the back scattering of white light. gel-trapped TiO(2) minimizes the oxidative stress exerted by UV radiation, increases the photo-stability of some accompanying ingredients, such as avobenzone. The size of the particles is in the micrometre range. This favors their permanence on the top of the stratum corneum. Gel-trapped TiO(2)-based sunscreens provide a larger SPF and two-fold larger UVA protection than equal-composition sunscreens that contain larger amounts of untrapped TiO(2).

A novel method to study the skin-lightening effect of topical materials.

Skin without significant dyschromia is an aesthetic requirement for people worldwide. There are several in vitro methods to determine the whitening potential of actives; however, the in vivo testing of skin whiteners is a long and expensive process. We have designed a rapid clinical method to screen potential skin whiteners using a UV-induced skin tan as a model. Small areas of identical suntan are repeatably induced on the skin, and treatment of these sites allows rapid screening of several skin whiteners within the course of a month. The method provides reproducible results and valuable information about the potential skin-lightening activity of topical preparations.

A rapid method to clinically assess the effect of an anti-acne formulation.

Historically, clinical evaluation of acne treatment has been based on direct visual assessment and the counting of lesions over a period of several weeks of treatment. However, with advancing technology there has been ever-increasing speed in the effectiveness of these treatments. To successfully assess these faster treatments, acne pathology needs to be evaluated in a shorter time frame. The object of these studies was to develop techniques to evaluate individual acne lesions in a shorter time frame and to assess speedier treatment technologies. Ten healthy volunteers with acne lesions on their upper backs were recruited for the study. Two inflamed acne lesions were selected for each treatment, along with lesions to be left untreated, on each volunteer. Each lesion was marked, photographed, and visually graded. A skin surface microscope (Scopeman) was used to visualize size and to grade the lesions by two experts every day for five days. The sites were treated once a day for the course of the study. There was a remarkable reduction in the size and erythema of acne lesions after treatment with the acne formulation as compared to the untreated and vehicle-treated lesions. Individual lesions, both treated and untreated, appeared resolved in 14 days. This resolution can be noticeably accelerated by topical treatments. We have developed a simple and faster clinical method to evaluate the effects of topical anti-acne technology.

Neuropeptide (calcitonin gene-related peptide) induction of nitric oxide in human keratinocytes in vitro.

Nitric oxide (NO) is an important signaling molecule in both the central nervous system and the periphery, where it is involved in neurotransmission, vascular and bronchial tone, inflammation, and cutaneous immune function. More recently, NO has been implicated in intracellular signaling and may have a role in cellular differentiation, cytokine expression, and apoptosis. The experiments described herein examined the effect of calcitonin gene-related protein (CGRP), a cutaneous nerve neuropeptide, on NO production in human keratinocytes in vitro. CGRP stimulated two distinct increases in NO production: one within 30 minutes and a second at 24 hours. CGRP stimulated a modest increase in inducible nitric oxide synthase (iNOS) at 3-6 hours. Experimental evidence suggested that CGRP stimulated both constitutive NOS activity and generation of NO via nitrosothiol degradation within the first hour. Production of NO was paralleled by a decrease in nitrosothiol levels for 2 hour, suggesting that immediate NO release may originate from pre-existing stores. Nitrosothiols are ubiquitous molecules that comprise an important NO pool and have intracellular regulatory roles, particularly linked to oxidative stress. The present data indicate that, in addition to its known cAMP signaling pathway, CGRP may act to regulate keratinocyte biology through intracellular NO by modulation of S-nitrosothiol stores and stimulation of NOS activity.

Effect of systemic hormonal cyclicity on skin.

Fluctuations in estrogen and progesterone during the menstrual cycle can cause changes in body systems other than the reproductive system. We conducted several studies to determine a possible correlation between phases of the menstrual cycle and specific skin properties. Healthy Caucasian women (ages 21-48), who had a typical 26-29 day menstrual cycle, participated in the studies. Measurements of skin barrier strength, dryness, response to lactic acid stinging, skin surface lipids, and microflora were obtained every week for two to three months. Ultraviolet B susceptibility in terms of minimal erythemal dose was also studied. The skin barrier was the weakest between days 22 and 26 of the cycle. Elevated neuronal response (lactic acid sting) was not observed to vary much with the cycle. Skin was driest between day 1 and day 6, while skin surface lipid secretion appeared to be highest on days 16-20 of the hormonal cycle. The highest microbial count was around days 16-22, and there was a high UV-B susceptibility between days 20 and 28 of the menstrual cycle.

Impact of stress of marital dissolution on skin barrier recovery: tape stripping and measurement of trans-epidermal water loss (TEWL).

BACKGROUND: Psychological stress of marital disruption is associated with significant increases in a variety of psychological and physical disorders. The effect of stress on the immune system is well documented and skin disorders have been reported to exacerbate during stressful situations. This study was designed to observe the effects of stress on skin barrier strength and recovery. Twenty-eight healthy females age 21-45 who were in the process of marital separation were tested for skin barrier strength and recovery. The panel was chosen on the basis of the intensity of self perceived stress. The control group was an age-matched group of self perceived 'happy' subjects. Servomed evaporimeter was used to measure trans-epidermal water loss (TEWL) from cheek area of the face, before and after removing stratum corneum layers with tape strippings. Skin barrier strength was defined as the number of tape strippings required to disrupt skin barrier, which is a TEWL of 18 g/m2/h or more. Barrier recovery was denoted by the level of TEWL, 3 h and 24 h after barrier disruption. RESULTS: There was no correlation between the degree of stress and barrier strength. However, individuals with high stress recovered slower than the individuals with low stress after 3 h (R = 0.64) and 24 h (R = 0.74). CONCLUSIONS: Psychological stress of marital dissolution does not appear to change skin barrier strength but has a negative impact on skin barrier recovery.

Tonality of suntan vs sunless tanning with dihydroxyacetone.

BACKGROUND/AIMS: Although there is an increasing awareness of the detrimental effects of solar irradiation on skin, a tanned look is still in fashion. To achieve the tanned look without sun exposure various sunless tanning formulations have become available. Most of these contain dihydroxyacetone (DHA) which binds to the proteins of the stratum cornium and imparts a brown color to skin. This color is similar to a suntan but can be somewhat more yellow, making it appear unnatural. The aim of this study was to determine a quantitative method to define a "natural" tan and to study methods to improve the tonality of sunless tanning on skin. METHODS: Tonality of suntan was determined as the marker for a "natural" tan. In order to achieve this, human volunteers were exposed to the sun and the change in skin color was observed after 3 days. Color measurements obtained with the Minolta Chromameter were plotted in two standard graphs labeled as the "natural universe of tan", which depicted a balance between Chroma and change in reflectance, while the "natural universe of color" determined the balance between changes in yellow and red components of the suntan. Change in skin color after treatment with DHA was then inserted in these graphs to observe how "natural" the tonality of sunless tan appeared relative to suntan. RESULTS: Results show a good balance between Chroma and change in reflectance for suntanned skin in the "natural universe of tan". Conversely, the "natural universe of color" exhibited a good balance between increase in yellow and red components of suntan. Sunless tan data inserted in these graphs showed that for several subjects with skin types I-II the tonality is not within the realm of "natural" but is unnaturally yellow. Addition of antioxidants, especially caffeic acid phenethyl ester (CAPE) in DHA formulation significantly shifted the tonality towards the center of the "natural universe of color". CONCLUSIONS: The "natural universes of tan and color" exhibit a simple and quantitative assessment of tonality of suntan and sunless tan. Although skin tonality from DHA-induced sunless tan can often lie outside the realm of the "natural" tan, it is possible to improve this tonality to a more "natural" look by addition of strong antioxidants in the DHA formulations.