Calmodulin-like skin protein level increases in the differentiated epidermal layers in atopic dermatitis.

In atopic dermatitis (AD), the skin barrier is disturbed, and the expression of calcium-dependent S100 proteins and the calcium gradient is also altered in the epidermis. The calmodulin-like skin protein (CLSP), which is expressed in the differentiated epidermis, is believed to modulate the function of calcium-dependent proteins involved in barrier formation and is significantly increased in the epidermis of psoriatic patients. We, therefore, investigated the CLSP level in skin biopsies taken from patients with acute exacerbated and non-exacerbated AD as well as from healthy control subjects. Immunohistochemical, Western blot and ELISA analyses showed significant increases (P < 0.03) in CLSP level in the epidermis from patients with acute exacerbated AD as compared to that from patients with non-exacerbated AD and from control subjects. Such increased expression of CLSP may help re-establish a functional epidermal barrier in acute AD.

Actinic lentigines from Japanese and European volunteers share similar impaired biological functions.

BACKGROUND: Hyperpigmented spots develop earlier and with a higher incidence in Asian individuals compared with Europeans. Although actinic lentigines (AL) are very common, the biological events underlying their formation remain ill-defined. OBJECTIVE: AL from Japanese volunteers were characterized through morphological and gene expression analyses. Data were then compared with published data on European volunteers. METHODS: AL on hands were selected through dermoscopic imaging and pattern scoring in Japanese women. Skin biopsies of AL and adjacent non-lesional (NL) skin were processed for histology and gene expression profiling. Japanese and European studies were compared after harmonizing the data using the same mathematical and statistical methods. RESULTS: Histologically, AL from Japanese individuals revealed deep epidermal invaginations with melanin accumulation in the depth of epidermal rete ridges. Transcriptomic data identified 245 genes differentially expressed in AL versus NL skin samples, associated with the different skin compartments and multiple functional families and biological processes, such as epidermal homeostasis, extracellular matrix organization and ion binding/transmembrane transport. Strikingly, melanogenesis-related genes were not significantly modulated in AL compared with NL skin. Comparison of the molecular profiles of Japanese and European AL showed that a huge majority of genes were modulated in the same way, recapitulating the overall biological alterations. CONCLUSION: AL from Japanese volunteers exhibited morphological and molecular alterations of the whole skin structure with impairment of multiple biological functions similar to that found in European women. These findings will contribute to the development of efficient treatments of AL lesions.

Ethnic variations in facial skin neurosensitivity assessed by capsaicin detection thresholds.

BACKGROUND: Ethnic variations in sensitive skin have not been thoroughly explored and remain controversial. OBJECTIVE: To objectively assess ethnic variations in facial skin neurosensitivity through individual detection thresholds of topically applied capsaicin. PATIENTS/METHODS: The single-blind, controlled study was performed in 144 women from three ethnicities: Asian, African, and Caucasian. Five solutions with increasing capsaicin concentration were successively applied to one side of nasolabial folds, while the other side simultaneously received the vehicle as control. The test was discontinued when the volunteer reported on the capsaicin side a sensation whatever its nature. Otherwise the experimenter continued the test, using the next solution with higher capsaicin content and so on, until the subject experienced a sensation on the capsaicin side. RESULTS: Each ethnic group was divided into six sub-groups according to the level of sensitivity to capsaicin, i.e. from detection of the lowest concentration up to no detection of the highest concentration, 100-fold higher. Asian women tended to have higher capsaicin detection thresholds than Caucasians, but lower thresholds than Africans. Nevertheless, the distribution did not greatly differ between the three ethnicities. CONCLUSIONS: The capsaicin skin neurosensitivity test is painless and the changes across individuals of different ethnic backgrounds appear minimal.

Pharmacologic study of C-terminal fragments of frog skin calcitonin gene-related peptide.

The calcitonin gene-related peptide from the skin of the frog Phyllomedusa bicolor (pbCGRP) is a 37-residue neuropeptide that differs from human alpha CGRP (halphaCGRP) at 16 positions. The affinities of the C-terminal fragments of pbCGRP and halphaCGRP were evaluated in SK-N-MC cells: pbCGRP(8-37) (K(i)=0.2nM) and pbCGRP(27-37) (K(i)=95nM) were, respectively, 3 times and 20 times more potent than the human fragments halphaCGRP(8-37) and halphaCGRP(27-37). Their antagonistic potencies were measured in SK-N-MC and Col 29 cells, and the rat vas deferens. pbCGRP(8-37) inhibited the halphaCGRP-stimulated production of cAMP by SK-N-MC and Col 29 cells 3 to 4 times more strongly than halphaCGRP(8-37). Thus pbCGRP(8-37) is the most potent CGRP-1 competitive antagonist of all the natural sequences reported to date. pbCGRP(27-37) was also as potent as [D(31), A(34), F(35)] halphaCGRP(27-37), a prototypic antagonist analog derived from structure-activity relationship studies of halphaCGRP(8-37).

Effects of topical DHEA on aging skin: a pilot study.

OBJECTIVES: Dehydroepiandrosterone (DHEA) is a steroid hormone involved in physiological aging. When administered by oral route, it has been shown to positively affect skin condition on aged people. The purpose of this pilot study was to observe the in vivo effects on skin aging of topical DHEA (1%). METHODS: The DHEA formulation (1%) or the vehicle was topically applied for 4 months to facial and hand skin, in two groups of 20 post-menopausal women. The efficacy of the treatment was evaluated on the basis of clinical and biophysical signs linked to skin aging. RESULTS: We showed that DHEA treatment increased the rate of sebum, which was perceived rather positively by a menopausal population usually affected with a declining sebum level. Topical DHEA tends to improve skin brightness, to counteract papery appearance of skin and epidermal atrophy, a characteristic feature of hormone-related skin aging. Topical DHEA could also act on skin process related to wrinkles, but this result remains to be confirmed. CONCLUSIONS: This pilot study showed beneficial effects on skin characteristics that are rarely provided by topical treatments. It raised some interesting clues towards the treatment of skin aging.

Neural basis of sensitive skin: an fMRI study.

BACKGROUND/PURPOSE: About 50% of women declare themselves to have sensitive skin. However, sensitive skin still appears to be a questionable problem not corresponding to a specific physiological pattern. To objectivate the neural basis of sensitive skin, we measured cerebral response to cutaneous provocative tests in self-perceived sensitive and non-sensitive skin subjects using functional magnetic resonance imaging (fMRI). METHODS: Subjects were divided into two groups according to their self-perceived characterization by using a dedicated questionnaire about their skin reactivity. Event-related fMRI was used to measure cerebral activation associated with skin discomfort induced by a simultaneous split-face application of lactic acid and of its vehicle. RESULTS AND DISCUSSION: In both groups, skin discomfort due to lactic acid increased activity in the primary sensorimotor cortex contralateral to application site and in a bilateral fronto-parietal network including parietal cortex, prefrontal areas around the superior frontal sulcus, and the supplementary motor area. However, activity was significantly larger in the sensitive skin group. Most remarkably, in the sensitive skin group only, activity spreaded into the ipsilateral primary sensorimotor cortex and the bilateral peri-insular secondary somatosensory area. Our results demonstrate that, compared with control subjects, self-perceived sensitive skin subjects have a specific cerebral activation during skin irritative test, which allows us to hypothesize that self-perceived sensitive skin is intrinsically linked to a specific neurophysiologic pattern for these subjects. CONCLUSION: This study demonstrates that fMRI is an effective objective method for measuring cerebral processes underlying skin reactivity and contributes to a better understanding of the neural basis of the sensitive skin phenomenon.

Low iron stores: a risk factor for excessive hair loss in non-menopausal women.

Iron deficiency has been suspected to represent one of the possible causes of excessive hair loss in women. The aim of our study was to assess this relationship in a very large population of 5110 women aged between 35 and 60 years. Hair loss was evaluated using a standardized questionnaire sent to all volunteers. The iron status was assessed by a serum ferritin assay carried out in each volunteer. Multivariate analysis allowed us to identify three categories: "absence of hair loss" (43%), "moderate hair loss" (48%) and "excessive hair loss" (9%). Among the women affected by excessive hair loss, a larger proportion of women (59%) had low iron stores (< 40 microg/L) compared to the remainder of the population (48%). Analysis of variance and logistic regression show that a low iron store represents a risk factor for hair loss in non-menopausal women.

Age-related changes in skin topography and microcirculation.

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.

Detection thresholds of capsaicin: a new test to assess facial skin neurosensitivity.

The goal of this study was to assess the accuracy/reliability of a new test designed to measure cutaneous neurosensitivity. The test was carried out on a random population of 150 healthy adult women and was based on the determination of individual detection thresholds of topically applied capsaicin. Five capsaicin concentrations were used in 10% ethanol aqueous solution (3.16 x 10(-5)%; 1 x 10(-4)%; 3.16 x 10(-4)%; 1 x 10(-3)%; 3.16 x 10(-3)%). The methodology used to attain the detection threshold was capsaicin application in increasing concentration on the nasolabial folds. The vehicle was simultaneously applied following a split-face, single-blind plan. The test was stopped as soon as the subject reported a specific sensation lasting more than 30 seconds on the capsaicin side. The safety of the test was judged as excellent by the panelists since all the reported sensations were considered as slightly or moderately perceptible. The test allowed the classification of the test population according to six threshold levels corresponding to the sensitive reaction to one of the five capsaicin concentrations and to the absence of sensitivity to the highest concentration. Surprisingly, the distribution of the population was not unimodal and seemed to reveal the existence of two different sub-groups: individuals with a low capsaicin detection threshold and those with a high threshold. These two sub-populations strongly differed in their respective self-perception of sensitive skin. The higher the self-declared sensitive skin incidence was, the lower the detection threshold was. This new test of skin neurosensitivity is easy, quick, and truly painless. It appears to be a promising tool for the cosmetic diagnosis of sensitive skin.

Histological features of peripilar signs associated with androgenetic alopecia.

BACKGROUND: A study of the scalp in a large cohort of volunteers with androgenetic alopecia using macrophotographs showed the presence of peripilar signs (PPS) around the hair ostia. OBJECTIVE: The aim of the present study was to establish the histopathological features related to PPS. DESIGN: Prospective clinicopathological study. SETTING. Department of Dermatology, University Hospital of Bologna. PATIENTS: A group of 40 patients (21 males and 19 females) participated in the study. Macrophotographs of the scalp were taken using a Dermaphot camera and PPS were scored using a three-point scale. Hair density and PPS were clinically scored according to reference scales. Two punch biopsies from the photographed area were obtained from each subject and histological analysis was performed on vertical and horizontal sections. OBSERVATIONS: Clinical parameters indicated that PPS were already detectable on scalp with high hair density. Moreover, in patients with high hair density (score >4), a significant relationship was found between the PPS score and the global score for perifollicular infiltrates. Thus PPS are linked to superficial perifollicular lymphocytic infiltrates in early androgenetic alopecia. CONCLUSIONS: PPS could be the clinical signs reflecting the presence of perifollicular infiltrates.

Skin complexion and pigmentary disorders in facial skin of 1204 women in 4 Indian cities.

BACKGROUND: The color of Indian skin shows great diversity and pigmentary disorders are a major concern of Indian women. Despite great variations in climate, diet, and social parameters within India, studies of the range of skin types have been rather scarce. AIMS: This study was aimed at characterizing the color of Indian skin in various geographical locations, its characteristics in terms of overall skin complexion and pigmentary disorders, and the impact of age on these features. METHODS: An extensive descriptive study, including skin color parameters (objective measurements and evaluations by dermatologists, clinically or from photographs) was carried out involving 1,204 female volunteers of different ages living in four different Indian cities. RESULTS: Important differences in skin complexion according to the geographical location were observed. Age seemed to have little impact on complexion. Hyperpigmented spots were frequent and were noted at early stages and many lentigines were found. Melasma affected about 30% of middle-aged women, but many other ill defined, pigmented macules were also observed. Additionally, we found pigmented lip corners associated with marionette lines, and linear nasal pigmentation. CONCLUSIONS: Indian skin color is diverse and pigmentary disorders are common. Skin complexion is not greatly affected by age. Some hyperpigmented disorders occur at early stages and increase with age, contributing to overall unevenness of facial color.

Age-related changes of the cutaneous microcirculation in vivo.

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.