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The aetiology of infraorbital dark circles is complex and multi-factorial. The aim of this research was to measure and characterize dark circles and to determine the physiological changes associated with the occurrence of this aesthetically unpleasing issue. Clinical, photographic and instrumental assessments were performed on Caucasian skin to determine the most appropriate methodologies to measure dark circles, comparing different zones of the infraorbital region in subjects with and without dark circles. Exploratory studies were also carried out on African and Far East Asian skin, as well as on tracking the natural variation of dark circles over seven days in Caucasian subjects. Under-eye dark circles in Caucasian subjects are characterized by significantly darker coloured skin and higher colour deviations between the dark circle region and surrounding areas of skin. Multispectral image analysis produced a higher melanin index in subjects with dark circles, suggesting hyperpigmentation in the affected area, in addition to a higher haemoglobin index. The higher haemoglobin index, combined with preliminary assessments of the vascular network by videocapillaroscopy, suggests there may be more dilated, thicker or increased numbers of capillaries in subjects with dark circles. Ultrasound analysis showed a significant difference in skin thickness between the two groups of subjects linking the appearance of dark circles to thinner skin under the eye. Many of these trends were also observed in African and Far East Asian skin. The results also showed intra-individual, intra-day and inter-day variability of dark circle intensity in subjects with Caucasian skin. Three key physiological factors associated with the occurrence of infraorbital dark circles are hyperpigmentation, a tendency for more dilated, thicker or increased number of capillaries and thinner skin in the under-eye area. The combination of these three factors provides a robust indication of the presence of infraorbital dark circles.

Background: Reactive oxygen species generated by ultraviolet light result in photocarcinogenic and photoaging changes in the skin. Antioxidants protect the skin from these insults. Objective: The aim of this study was to determine the ex vivo ascorbic acid penetration and its degradation in the skin after its topical application from an 8% new formulation. Method: Ascorbic acid was applied to human skin fragments. Ascorbic acid and its metabolites were collected by microdialysis and assessed by gas chromatography mass spectrometry. Results: After topical application of the new formulation, the ascorbic acid level achieved was 8.5% higher than the normal tissue value. This high ascorbic acid dermal concentration remained constant if a topical application was made every 8 h. No degradation of ascorbic acid was detected. Conclusion: Ascorbic acid penetrates rapidly after its topical application. The persistent reservoir of ascorbic acid provides an important and attractive photoprotection strategy.

Skin topography and microvasculature undergo characteristic changes with age. Although several non-invasive bioengineering methods are currently available to measure them quantitatively, few publications have referred to their relationship with age in different anatomical sites. This study was carried out to observe the age-related changes of the skin topography and skin microcirculation. The microrelief was assessed with special processing software from scanning by interference fringe profilometry of silicone replicas performed on two sites (volar forearm and back of hand) on 50 female volunteers (aged 20-74 years who consisted of ten probands in each decade). The superficial vascular network of both sites was assessed by videocapillaroscopy, and the subpapillary vascular plexus was studied with laser Doppler flowmetry. Skin color, which is affected by blood flow, was observed by colorimeter. The skin roughness and the mean height between peak and valley increased with age. There were statistically significant differences between the evaluated sites. This study also shows that the capillary loops in the dermal papillae decrease but the subpapillary plexus increase with age. The interference fringe profilometry associated with videocapillaroscopy may be useful and accurate to measure the efficacy of medical or cosmetic products to delay skin aging.

Several studies have confirmed dramatic changes in skin surface parameters during the winter months. Although there are many studies supporting the positive effects of topical treatment, there are no published studies demonstrating the effects of oral supplementation in the prevention of negative skin changes during winter. The purpose of this study was to evaluate the efficacy of an oral micronutrient supplement in preventing the negative effects of winter weather on skin quality using noninvasive biometrologic instruments. This study included 80 healthy female volunteers aged 35-55 years with phototype II-IV skin. Randomization was balanced. Two tablets of a micronutrient supplement (Perfectil® Platinum) or placebo were administered once daily for 4 months. The volunteers were examined at baseline, after 4 months, and 6 weeks after termination of treatment (month 5.5). The evaluation included skin microrelief by Visioscan® as the main outcome, and the secondary outcomes were results on standard macrophotography, skin tension by Reviscometer®, skin high-frequency ultrasound, and self-assessment. For all pseudoroughness and microrelief indicators, there was a significant increase from baseline to month 4 in the placebo group (P<0.05) but no change in the active group. Descriptive statistics for the mean minimum, mean maximum, and minimum to maximum ratio on the nonexposed study zone showed a significant and dramatic difference between baseline and month 4 and between baseline and month 5.5 (P<0.05) in the active group, indicating decreasing anisotropy of the skin. High-frequency ultrasound on the exposed study zone revealed that skin thickness was significantly decreased in the placebo group during winter but was stable in the treated group (P<0.01). The photography scaling and self-assessment questionnaire revealed no significant changes in either group. These results indicate that the skin is prone to seasonal changes during winter, particularly in exposed areas. The data also indicate that oral supplementation can be a safe treatment, with no serious side effects, and may prevent or even eliminate the negative effects of winter on the skin.

Background: The architectural frameworks of the skin microcirculation are rather complex and change continuously with aging. But these changes are yet poorly documented in vivo. Objectives: Using non-invasive methods belonging to the field of biometrology, the study aimed to investigate quantitatively the changes of the cutaneous microvasculature in different anatomic sites with age. Methods: Measurements were performed on crow’s feet, forehead, volar forearm and dorsum of hand in 50 women (aged 20–74 years who consisted of 10 probands in each live decades). The superficial vascular plexus was scanned by videocapillaroscopy and assessed with the software Capilab Toolbox ® . The subpapillary vascular plexus was explored with laser Doppler flowmetry. The skin color a* was analyzed by chromametry. Results: A marked site and age effect on the skin microcirculation has been demonstrated. The density of capillary loops in the eldest group decreased by about 40–70% compared with the youngest group whereas the vascular length increased by 35–156%. The capillary density in the back of the hand was 4 times higher than in the crow’s feet. The vascular length in the crow’s feet was 3 times longer than in the back of the hand. Both blood flow and skin redness (a*) increased also with age. Conclusion: Both morphology and quantification of the cutaneous microvasculature showed changes with site and age. Videocapillaroscopy associated to an image processing and laser Doppler flowmetry revealed different vascular layers. So the combination of both instruments offers an easy way to observe the architectural frameworks in vivo.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease in which reactive oxygen species (ROS) may be involved. Iron catalyses ROS formation and ascorbic acid (AA) scavenges these species. Objective: The aim of this work was to determine iron and AA levels in AD patients’ dermis and to compare their concentrations with those of healthy volunteers’ dermis. Methods: Five AD patients and 5 healthy subjects (controls) were enrolled in this study. Iron and AA were collected from human dermis by microdialysis and assessed by atomic absorption spectrometry and gas chromatography-mass spectrometry, respectively. Results: The AD dermis demonstrated higher iron concentrations (44.3 ± 4.6 µg/l) compared to controls (21.8 ± 1.2 µg/l) as well as a significantly lower concentration of AA (46.7 ± 0.6 vs. 176.8 ± 14.5 µg/ml, respectively). Conclusion: These results suggest that iron and AA dermis levels could be indicators of inflammatory tissues and might be implicated in dermatological diseases such as AD.

Background Rosacea is a common condition characterized by transient or persistent central facial erythema, and often papules and pustules. Currently, the role of bacterium in the development and progression of rosacea remains controversial. This study aimed to investigate the difference in the physiological conditions and microorganisms between the lesional and non‐lesional areas of papulopustular rosacea. Methods Twenty‐five French patients with papulopustular rosacea were enrolled in this pilot study. Each patient was subjected to clinical assessment, and the skin barrier function was tested in lesional and non‐lesional areas. In addition, samples from the lesional and non‐lesional areas were collected for bacterial culturing. Results Of all subjects included in the study, a lower skin conductivity was measured in lesional areas than in non‐lesional areas (43.5 ± 12.4 vs. 57.2 ± 11.6 U, P < .05), and a higher transepidermal water loss (TEWL) value was found in lesional areas than in non‐lesional areas (17.2 ± 5.9 vs. 14.2 ± 4.1 g/(m2 h), P < .05). We found a lower TEWL in lesions in rosacea patients with bacterial dysbiosis than in those with bacterial balance (P < .05). In addition, there were significant differences in the skin conductivity and TEWL between lesional and non‐lesional areas in patients with bacterial dysbiosis (P < .001), and no significant differences were seen in patients with bacterial balance (P < .05). Conclusion The results of the present study demonstrate that the physiological features of rosacea are closely associated with the interactions between the host and the microorganisms.

Background: Published studies assessing whether asymmetric facial ultraviolet light exposure leads to underlying differences in skin physiology and morphology are only observational. The aim of this study was to assess the visual impact on the skin of repeated ultraviolet-A (UVA) exposure through a window. Methods: Eight women and two men presenting with asymmetric signs of photoaging due to overexposure of one side of their face to the sun through a window over a long period of time were enrolled in the study. Split-face biometrologic assessments were performed (clinical scoring, hydration with Corneometer®, mechanical properties with a Cutometer®, transepidermal water loss with AquaFlux®, skin relief with fringe projection, photography, stripping, and then lipid peroxidation analyses). Results: Significant differences were observed in clinical scores for wrinkles, skin roughness assessed by fringe projection on the cheek, and skin heterogeneity assessed with spectrocolorimetry on the cheekbone. Other differences were observed for skin hydration, as well as skin laxity, which tended towards significance. Discussion: This study suggests the potential benefit of daily UVA protection during nondeliberate exposure indoors as well as outside.

MSH2 and MLH1 have a central role in correcting mismatches in DNA occurring during DNA replication and have been implicated in the engagement of apoptosis induced by a number of cytotoxic anticancer agents. The function of MLH1 is not clearly defined, although it is required for mismatch repair (MMR) and engagement of apoptosis after certain types of DNA damage. In order to identify other partners of MLH1 that may be involved in signalling MMR or apoptosis, we used human MLH1 in yeast two-hybrid screens of normal human breast and ovarian cDNA libraries. As well as known partners of MLH1 such as PMS1, MLH3 and MBD4, we identified the carboxy terminus of the human c-MYC proto-oncogene as an interacting sequence. We demonstrate, both in vitro by yeast two-hybrid and GST-fusion pull-down experiments, as well as in vivo by coimmunoprecipitation from human tumour cell extracts, that MLH1 interacts with the c-MYC protein. We further demonstrate that the heterodimeric partner of c-MYC, MAX, interacts with a different MMR protein, MSH2, both in vitro and in vivo. Using an inducible c-MYC-ER™ fusion gene, we show that elevated c-MYC expression leads to an increased HGPRT mutation rate of Rat1 cells and an increase in the number of frameshift mutants at the HGPRT locus. The effect on HGPRT mutation rate is small (2–3-fold), but is consistent with deregulated c-MYC expression partially inhibiting MMR activity.

Published studies assessing whether asymmetrical facial ultraviolet light exposure leads to underlying differences in skin physiology and morphology report only clinical observations. The aim of this study was to assess the visual impact on the skin of repeated ultraviolet-A (UVA) exposure through a window. Eight women and two men presenting with asymmetrical signs of photoaging due to overexposure of one side of their face to the sun through a window over a long period of time were enrolled in the study. Split-face biometrologic assessments were performed (clinical scoring, hydration with Corneometer, mechanical properties with Cutometer, transepidermal water loss with AquaFlux, skin relief with fringe projection, photography, stripping, and then lipid peroxidation analysis). Significant differences were observed in clinical scores for wrinkles, skin roughness assessed by fringe projection on the cheek, and skin heterogeneity assessed with spectrocolorimetry on the cheekbone. Other differences were observed for skin hydration, as well as skin laxity, which tended towards significance. This study suggests the potential benefit of daily UVA protection during nondeliberate exposure indoors as well as outside.