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Abstract. Background: Methylsulfonylmethane (MSM) is an organosulfur compound with known benefits for joint health, sports nutrition, immune function, and anti‐aging formulations and is gaining popularity as a nutritional supplement for the support of hair, skin and nails. Methods: The study was conducted in two steps; in Part I (pilot study) a panel of 20 participants ingested either 3 g a day of MSM or placebo capsules for 16 weeks. Visual and subject self assessment of wrinkles and skin texture as the predominant sign of ageing was observed. In Part II (dose-response study), 63 participants ingested either 1 g or 3 g per day of MSM for 16 weeks. Expert clinical grading, instrumental measurements and consumer perception was used to evaluate skin conditions like lines and wrinkles. Additionally, instrumentational analysis was conducted using corneometer and cutometer for investigation of skin hydration, firmness and elasticity. Results: Part I of the study clearly indicates that oral ingestion of MSM (3 g/d) reduces signs of ageing like facial wrinkles ( p

Omeprazole is a proton pump inhibitor used in the treatment of peptic ulcer disease and gastrosophageal reflux disease and acts by irreversibly blocking ATP4A, a P-type H+/K+ ATPase in gastric parietal cells. We found that omeprazole and its closely related congeners inhibited melanogenesis at micromolar concentrations in B16 mouse melanoma cells, normal human epidermal melanocytes, and in a reconstructed human skin model. Omeprazole topically applied to the skin of UV-irradiated human subjects significantly reduced pigment levels after 3 weeks compared with untreated controls. Omeprazole had no significant inhibitory effect on the activities of purified human tyrosinase or on the mRNA levels of tyrosinase, dopachrome tautomerase, Pmel17, or MITF mRNA levels. Although melanocytes do not express ATP4A, they do express ATP7A, a copper transporting P-type ATPase in the trans-Golgi network that is required for copper acquisition by tyrosinase. ATP7A relocalization from the trans-Golgi network to the plasma membrane in response to elevated copper concentrations in melanocytes was inhibited by omeprazole. Omeprazole treatment increased the proportion of EndoH sensitive tyrosinase, indicating that tyrosinase maturation was impaired. In addition, omeprazole reduced tyrosinase protein abundance in the presence of cycloheximide, suggestive of increased degradation. Our findings are consistent with the hypothesis that omeprazole reduces melanogenesis by inhibiting ATP7A and by enhancing degradation of tyrosinase.

Background/aims: Within the past three decades, there has emerged a greater awareness of the molecular effects of solar rays especially ultraviolet radiation (UV-R), to the extent that the harmful effects of solar radiation are recognized not only by molecular biologists and physicians, but also by the general public (1). Various sunscreen molecules that effectively block the UVB component of the sun are available; however, a large part of Western populations elicits adverse reactions against chemical sunscreens (2). This study was designed to observe the protective effect of antioxidants against the damaging effects of chronic UVB exposure of skin in an attempt to introduce antioxidants and free radical scavengers as topical sun protective agents. Methods: Jackson hairless mice were exposed to suberythemal doses of UVB, three times a week, and topically treated with a cream containing the anti-oxidants vitamin E, butylated hydroxy-toluene, nordihydroguaradinic acid and vitamin C. Results: Treatment with vehicle alone along with UVB exposure resulted in an increase in epidermal thickness showing a 38%, 77% and 112% increase after 4 weeks, 8 weeks and 12 weeks, respectively. Chronic UVB exposed skin treated with the material containing free radical scavengers and antioxidants mix (AO mix) exhibited 39%, 73% and 124% thicker epidermis than the un-treated control after, respectively, 4 weeks, 8 weeks and 12 weeks of treatment. The vehicle did not appear to protect skin against UV irradiation, since there appeared to be more (16%) sunburn cells in vehicle treated skin than the untreated, UV exposed skin after 4 weeks of treatment. After 8 weeks and 12 weeks, there were 33% and 36% less sunburn cells in the vehicle treated skin than the untreated, UV exposed skin. The antioxidant mix was significantly effective (P=

Advanced glycation end products (AGEs) and oxidation products (OPs) play an important role in diabetes complications, aging, and damage from sun exposure. Measurement of skin autofluorescence (SAF) has been promoted as a noninvasive technique to measure skin AGEs, but the actual products quantified are uncertain. We have compared specific SAF measurements with analytically determined AGEs and oxidative biomarkers in skin collagen and determined if these measurements can be correlated with chronological aging and actinic exposure.SAF at four excitation (ex)/emission (em) intensities was measured on the upper inner arm ("sun protected") and dorsal forearm ("sun exposed") in 40 subjects without diabetes 20-60 years old. Skin collagen from the same sites was analyzed by liquid chromatography-tandem mass spectrometry for three AGEs-pentosidine, carboxymethyllysine (CML), and carboxyethyllysine (CEL)-and the OP methionine sulfoxide (MetSO).There was poor correlation of AGE-associated fluorescence spectra with AGEs and OP in collagen, with only pentosidine correlating with fluorescence at 370(ex)/440(em) nm. A little-studied SAF (440(ex)/520(em) nm), possibly reflecting elastin cross-links, correlated with all AGEs and OPs. Levels of CML, pentosidine, and MetSO, but not SAF, were significantly higher in sun-exposed skin. These AGEs and OPs, as well as SAF at 370(ex)/440(em) nm and 440(ex)/520(em) nm, increased with chronological aging.SAF measurements at 370(ex)/440(em) nm and 335(ex)/385(em) nm, except for pentosidine, which correlated with fluorescence at 370(ex)/440(em), correlate poorly with glycated and oxidatively modified protein in human skin and do not reflect actinic modification. A new fluorescence measurement (440(ex)/520(em) nm) appears to reflect AGEs and OPs in skin.

Background Differences in structural and functional skin characteristics have been linked with ethnical background. But racial differences in skin have not been thoroughly investigated by objective methods and the data are often contradictory. Objectives This study was undertaken to compare skin barrier-related parameters of the stratum corneum on African American, Caucasian and East Asian skin by objective measurements. Methods Baseline values of trans epidermal water loss were collected on the face. Consecutive stratum corneum D-squame® tape strippings were collected on the panelist's ventral forearm and face to evaluate skin barrier strength and cohesion. Stratum corneum ceramides, maturation, measured as the transglutaminase-mediated cross-linking of stratum corneum proteins, and stratum corneum trypsin like enzyme activity were measured on the D-squame® tape strippings. Results East Asian and to some extent Caucasian skin was characterized by low maturation and relatively weak skin barrier. African American skin was characterized by low ceramide levels and high protein cohesion in the uppermost layers of the stratum corneum. These data can be interpreted in terms of the high prevalence of xerosis in black skin and increased skin sensitivity in East Asian skin. Conclusion These results demonstrate that skin properties at the level of the stratum corneum vary considerably among these ethnic groups. This contributes to an improved understanding of physiological differences between these study populations.

Skin hyperpigmentation, and the reactions that precipitate it, have been linked to free radicals by the fact that free radical scavengers or antioxidants can slow that hyperpigmentation. We have screened several hundred plant extracts for antioxidants and discovered one that is both a strong antioxidant and can reduce skin hyperpigmentation. Extracts of Dianella ensifolia contain 1-(2,4-dihydrophenyl)-3-(2,4-dimethoxy-3-methylphenyl) propane (DP), which was found to inhibit the free radical 1-1-diphenyl-2-picryl-hydrazyl (DPPH) with an EC(50) value of 78 mum. DP was also found to inhibit Ultraviolet (UV)C-induced lipid oxidation with an EC(50) of about 30 mum. We next investigated the effects of this antioxidant on skin hyperpigmentation. The reduction of discoloration by different topical treatments has been assessed in human volunteers using an in vivo assay for the rate of fading of UVB-induced tan. Two pharmaceutical formulas containing 4% hydroquinone (HQ) were used as positive controls, and we tested the ability of DP, a plant-derived amphoteric antioxidant, to increase performance of non-HQ cosmetic formulations. We found that the cosmetic formula containing DP produced an increase in the rate of fading compared to the two pharmaceutical treatments containing HQ.

The estimated apparent age (EAA) was estimated by a panel of trained experts, for the individuals in a cohort. Twelve independent clinical, biophysical and biochemical parameters measured on facial skin, have been identified by multiple regression analysis, which influence the EAA of a person of chronological age (CA) (under eye lines, clinically assessed crow’s feet, age spots, clinically evaluated firmness, forehead lines, pores, lip lines, instrumentally evaluated firmness, instrumentally evaluated crow feet, skin texture, in vivo fluorescence related to proliferation and glycation). An algorithm has been devised to obtain the calculated age score (CAS) in a cohort of 452 female volunteers, as $$ {\text{CAS}}(n )= \Upsigma C_{i} P_{i} (n)\quad (i = 1{-}13,n = 1{-}452\,{\text{and}}\,P_{13} = 1) $$ where the coefficients Ci are obtained by minimizing the difference EAA − CAS, and Pi(n) are the experimental values of the i-th parameter for the n-th volunteer. The determination of CAS before and after a specific cosmetic or pharmacological anti-aging treatment can be used to objectively assess the efficacy of the treatment. The comparison of EAA(n) and of CAS(n) with CA(n) allows one to predict the susceptibility of an individual’s face to undergo aging. It has been observed that the biophysical and biochemical parameters play a relevant role in the assessment of the predisposition of skin to undergo accelerated aging.

Glycation is the non-enzymatic reaction between reducing sugars and proteins that leads to the formation of advanced glycation end products (AGEs). In vivo skin autofluorescence (lambda(ex)/lambda(em)=370/440 nm) was used as a non-invasive clinical tool to study skin AGE accumulation in healthy panellists. Using multiple linear regression analysis, it was shown that for panellists below the age of 40, glycation associated in vivo skin fluorescence intensity increased as a function of chronological age and body mass index (BMI). Above the age of 40, the fluorescence was associated to age but not to BMI, suggesting that the effect of age became dominant over BMI. Since the accumulation of AGEs is expected to affect the biomechanical properties of the skin, in vivo skin elasticity data were gathered on a second panel. It was found that skin elasticity depended on age and BMI in a similar fashion as to what we observed for the skin fluorescence data. It is hypothesised that skin AGE accumulation contributes to the loss of skin elasticity in aged and/or overweight people.

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.

Background/aims: This study was designed to observe the effect of a mix of commercial antioxidants and free radical scavengers (AO) on protection of human skin against different wavelengths of the solar spectrum: 280-320 nm (UVB), 320-400 nm (UVA) and 400-900 nm (IR). Methods: Healthy volunteers were chosen from the local population and exposed to the three aspects of the solar spectrum. Erythema at 24 h, immediate pigment darkening (IPD) and immediate erythema were employed as markers for UVB, UVA and IR exposure, respectively. Results: Based on 24 h erythema measurements, the AO mix afforded about 2.6-fold (163%) protection against UVB-induced erythema (Table 1). IPD measurements after UVA exposure exhibited 76% protection afforded by the AO mix. The AO mix reduced IR-induced increases in erythema and blood flow by 43% and 52%, respectively (Table 1). Conclusions: Data from these studies suggest that treatment with antioxidants prior to exposure to solar irradiation allows protection of human skin against IR as well as UVB and UVA. Antioxidants and free radical scavengers may be valuable adjuncts to traditional sunscreens, for protection of skin against the effects of actinic exposure that, over a long term, can result in formidable consequences such as skin cancer and photo-aging.

Background: Users of cosmetics and skin care products often report adverse reactions ranging from itching and dryness to intense inflammatory responses such as erythema or wheal and rash. Self-assessment is not always an accurate parameter for categorizing skin as sensitive or nonsensitive, although it can be valuable. For this reason, it is important to define sensitive skin by more objective factors. Objective: Studies were undertaken to determine if objective biophysical measurements could detect differences in barrier function between those individuals who identified themselves as having sensitive skin and those self-identified as having normal skin. In addition, the effects of treatment on barrier functions of individuals with sensitive skin were determined. Methods: Three main factors that contribute to cutaneous reactivities were observed for the estimation of skin sensitivity: barrier functions, reactivity to irritants, and neuronal responses manifested as sensory reactions. Barrier functions of the skin was tested by gentle removal of the stratum corneum with simple cellophane tape stripping followed by measurement of transepidermal water loss (TEWL) as a marker of barrier loss. The onset and intensity of skin reaction against an irritant, balsam of Peru, was tested on the same individuals to observe the reactivity of their skin. Using the lactic acid sting test, additional information regarding skin sensitivities was obtained. Results: Sensitive skin individuals exhibiting easy barrier damage possess delicate skin that is also highly reactive to irritants. When these individuals used a regimen of products that contained minimal preservatives and no surfactants for 8 weeks, the skin barrier and reactivity changed such that it was similar to nonsensitive skin. Conclusions: Skin sensitivity is observed because of a combination of factors, including a disrupted barrier and a tendency to hyperreact to topical agents. Treatment with special topical skin care formulations can reduce overall skin sensitivity.

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.

The primary goal of the present research was to determine whether sulfated polysaccharides derived from red microalgae possess antiinflammatory properties when directed against specific parameters of human skin inflammation. These unique biopolymers were studied in both in vitro and in vivo models of skin inflammation. Human subjects were recruited to participate in a study in which the polysaccharide material was applied topically and shown to inhibit cutaneous erythema induced by a known irritant. Leukocyte migration from capillary blood into sites of inflammation is an essential component of the inflammatory process and occurs in a series of steps, two of which are adhesion and chemotaxis. In vitro, the polysaccharide material primarily inhibited the migration of polymorphonuclear leukocytes (PMNs) toward a standard chemoattractant molecule and also partially blocked adhesion of PMNs to endothelial cells. The data obtained strongly suggest that sulfated polysaccharides derived from red microalgae have significant beneficial potential for use in topical products. In addition, the data suggested that the antiinflammatory mechanism for the polysaccharide was, at least in part, due to inhibition of circulating immune cell recruitment toward inflammatory stimuli.

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.

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.