Specific gene expression signature associated with development of autoimmune type-I diabetes using whole-blood microarray analysis.

Understanding the pathogenesis of type-I diabetes (T1D) is hindered in humans by the long autoimmune process occurring before clinical onset and by the difficulty to study the pancreas directly. Alternatively, exploring body fluids and particularly peripheral blood can provide some insights. Indeed, circulating cells can function as 'sentinels', with subtle changes in gene expression occurring in association with disease. Therefore, we investigated the gene expression profiles of circulating blood cells using Affymetrix microarrays. Whole-blood samples from 20 first-degree relatives of T1D children with autoimmune diabetes-related antibodies, 19 children immediately after the onset of clinical T1D and 20 age- and sex-matched healthy controls were collected in PAXgene tubes. A global gene expression analysis with MDS approach allowed the discrimination of pre-diabetic subjects, diabetic patients and healthy controls. Univariate statistical analysis highlighted 107 distinct genes differently expressed between these three groups. Two major gene expression profiles were characterized, including type-I IFN-regulated genes and genes associated with biosynthesis and oxidative phosphorylation. Our results showed the presence of early functional modifications associated with T1D, which could help to understand the disease and suggest possible avenues for therapeutic interventions.

Use of the Reviscometer for measuring cosmetics-induced skin surface effects.

BACKGROUND/PURPOSE: The Reviscometer RVM600 that measures resonance running time (RRT) has been shown to be inversely related to the skin stiffness. However, very few publications describe the use of this instrument for testing the effect of cosmetic products. METHODS: Slight xerotic skin condition was induced by using an alkaline soap for 1 week. Skin has then been rehydrated with a lotion or further dehydrated and dried with sodium lauryl sulfate (SLS). Skin condition at the different stages of the study was evaluated by visual assessment for dryness and redness and by non-invasive methods (Corneometer, Cutometer, Reviscometer, Evaporimeter and squamometry). RESULTS: All methods showed highly significant changes after the slight drying phase with the soap usage. They illustrated skin repair after lotion treatment and further skin impairment after SLS application. Nevertheless, the Reviscometer was able to better statistically discriminate between the treatments (water, lotion, SLS) than the Cutometer . Measurement of the RRT along the transversal axis of the forearms was the most sensitive for differentiating between normal and dry skin and between the treatments on the basis of skin mechanical properties. CONCLUSION: The Reviscometer RVM600 is a sensitive instrument able to detect slight skin surface effect of cosmetics. Combined with published literature on the interpretation of RRT measurements on polymeric gel or in different skin conditions (elderly skin and photoaged skin), the Reviscometer looks to be a recommendable instrument to measure slight changes in SC stiffness/suppleness induced by cosmetic products.

EEMCO guidance for the efficacy assessment of antiperspirants and deodorants.

Overproduction of sweat, sweaty skin and body odours are unpleasant for many social groups. Body cleansing products are designed to combat these undesirable features of skin. In addition, antiperspirant and deodorant products are more specifically used in the underarm site by a large part of the adult population. Antiperspirants are offered to control emotionally triggered sweating in the armpit. Deodorants are designed to combat malodour generated from bacteria-modified sweat. This review summarizes the physiology of eccrine, apocrine and apoeccrine sweat glands. The mechanisms of action of antiperspirants and deodorants are described as well as the factors influencing their efficacies. A series of tests using various measurement methods can be used to demonstrate the efficacy of antiperspirants. These include the gravimetric method, water evaporation quantification, electrodermal measurements, staining procedures, dye injections and cyanoacrylate skin surface strippings and casting replicas. Deodorant efficacy can be evaluated by sensory assessments performed by an expert panel. Indirect support is provided by visualization of apocrine gland excretion and collection of sweat and volatile compounds. Microbiological assessments and chromatographic analysis also provide indirect information.

EEMCO guidance for the in vivo assessment of skin surface pH.

The pH of the skin follows a sharp gradient across the stratum corneum (SC), which is suspected to play an important role in controlling the enzymatic activities involved in cellular metabolism and renewal. This gradient is maintained by several systems, such as sweat and sebum secretion and degradation as well as cellular metabolism. At the surface of the skin, what is measured is in fact an apparent skin pH due to extracted material from the SC diffusing into water applied at the surface. pH values recorded at the surface of a semi hydrophobic milieu such as the SC should be interpreted with great caution because it is obvious that hydrogen ions are not in a pure solution at the surface of the skin. For a correct measurement of skin surface pH, it is recommended to follow all practical operating conditions. Care must be taken in identifying the skin site, healthy controls (age, gender, skin type), the time of day of the measurement and the environmental conditions. Also, subjects should receive precise instructions before the test, mainly in terms of hygiene procedure or use of topical products. The interpretation of data should not overlook the fact that even small differences in pH may reflect significant modifications at the molecular level. Although it is usually agreed that the pH of the skin surface may influence the cutaneous microflora, much remains to be learnt about the role of the acid mantle of the skin with regard to defensins and other protective mechanisms.

Hand and forearm skin: comparison of their respective responsiveness to surfactants.

BACKGROUND/AIMS: Skin compatibility of detergent products is usually evaluated using predictive tests where products are applied on the back or the forearm of the volunteers, even if those products come more readily into contact with consumers' hands. The current study aimed at comparing the skin responsiveness of hands and volar and dorsal forearms to a surfactant solution. METHOD: Volunteers soaked simultaneously their forearms and hands in a solution of anionic surfactants, at 40 degrees C for 20 min, thrice a day and for 2 consecutive days. Skin condition on the hands, and the volar and dorsal forearms was evaluated by clinical examination and instrumental measurements. RESULTS: Significant differences were observed at baseline for various skin parameters, especially those related to skin dryness. After repetitive contacts with the surfactant solution, a parallel evolution of most skin parameters was observed--i.e., an absence of change in instrumentally measured erythema and transepidermal water loss, a similar decrease in corneometry values, and a similar increase in staining of the stratum corneum strippings and in clinical dryness. However, an opposite effect of the soakings on the cohesiveness between corneocytes harvested by tape strippings from hand and forearm was observed. CONCLUSION: For most parameters, skin responsiveness to surfactants appears to be quite similar on the hands and forearms. It is inferred that forearms can be conveniently used to predict interaction of surfactants with hands.

A comparative study of the effects on the skin of a classical bar soap and a syndet cleansing bar in normal use conditions and in the soap chamber test.

BACKGROUND/AIMS: The skin irritation potential of a body cleansing product is often compared under exaggerated test conditions, although the product is intended to be used at home with repetitive and brief contact with the skin. The aim of this study was to determine how much patch testing is predictive of the clinical, sub-clinical and subjective cutaneous effects of products used at home by consumers for their normal hygienic cleansing. METHODS: A double-blind comparative study of the normal use of an alkaline soap bar and a syndet at home during 10 consecutive weeks was performed on two identical groups of 25 healthy female subjects. The eventual skin changes observed at different anatomical skin sites were evaluated by clinical visual examination and by bioengineering measurements before the start of the study and then every 2 weeks. The objective measurements were compared with the subject's perceptions of dryness, tightness and product irritancy during the testing. RESULTS: The bioengineering measurements did not show any significant changes on all the anatomical skin sites, except for a small increase in skin pH with the classical soap bar. However, a trend appeared, showing that the alkaline soap bar is perceived by the subjects themselves as more of an irritant than the syndet bar. In the soap chamber test, the bar soap showed a significantly higher irritancy than the syndet bar. CONCLUSION: This study showed that cutaneous irritation induced by cleansing products in patch testing is not necessarily predictive of the irritation likely to occur in normal use conditions. Finally, a clear relationship could be demonstrated between the results of the soap chamber test and the consumer perception of both cleansing bars.

Subclinical, non-erythematous irritation with an open assay model (washing): sodium lauryl sulfate (SLS) versus sodium laureth sulfate (SLES).

Compared to exaggerated hand washing procedures, an open non-exaggerated assay better approximates consumer surfactant use. Our goal was to observe skin surface modifications induced by an open test with regard to discriminating between surfactant solutions. This human in vivo assay provided information about the effect of only three washes at the laboratory and a week of at-home use. Dorsal hand and volar forearm were compared. The results demonstrated that this clinical model permits exploration of subclinical surfactant-induced irritation. Both the volar forearm and the dorsal hand are capable of discriminating between the effects of sodium lauryl sulfate (SLS) and sodium laureth sulfate (SLES). Squamometry proved to be a sensitive assessment technique for detecting surfactant-induced subclinical skin surface alterations and for differentiating surfactant effects in this open application assay, in as few as three washes.

EEMCO guidance for the in vivo assessment of skin greasiness. The EEMCO Group.

Sebaceous gland activity has four distinct components which are sebum production (a secretion rate function), storage (a volume function), surface output (a delivery rate function) and stratum corneum permeation (an influx rate function). The oily appearance of skin results from an excess of sebum excretion and spreading over the body surface and its interaction with the skin surface. A multi-pronged approach is often useful to assess skin greasiness with precision. The clinical evaluation of skin greasiness and its shiny appearance should be further complemented by quantifying the large pores, follicular plugs and comedones. The sebum amount present at the skin surface can be measured non-invasively using one of several methods based on solvent extraction, cigarette paper pads, photometric assessment, bentonite clay and lipid-sensitive tapes. Quantitative parameters include the sebum casual level, the sebum excretion rate, the sebum replacement time, the instant sebum delivery, the follicular excretion rate, the density in sebum-enriched reservoirs and the sustainable rate of sebum excretion. A series of environmental and biological features influence the data. Hence rigorous methodological designs are mandatory to support claims. As a rule, accuracy of the methods is adversely affected by skin temperature, degree of hydration and surface roughness. An additional confounding factor is the inherent difficulty of collecting the surface lipids without a contribution from the follicular reservoir. A better understanding of factors that alter the sebum amount at the skin surface may well assist in the development of sebosuppressive agents to help the reduction of the skin greasiness and improve acne.

An open assay model to induce subclincal non-erythematous irritation.

To avoid the acute irritation and dryness that a single occlusive surfactant application (24-h patch test) may cause, and to approximate clinical use, an open application model was chosen to define subclinical non-erythematous irritation in the stratum corneum. This human test combined a supervised washing at the laboratory with at-home use of the test products by the subjects. Effects of washing with the surfactants on the dorsal hand and volar forearm were compared. The results demonstrated that this situational use model permits the exploration of subclinical surfactant-induced irritation. The forearm appeared to be more discriminative as compared to the dorsal hand. Squamometry proved to be a sensitive, complementary assessment method for detecting surfactant-induced subclinical skin surface alterations and for differentiating surfactant effects in this open assay.

A hand immersion test under laboratory-controlled usage conditions: the need for sensitive and controlled assessment methods.

Exaggerated test conditions were frequently used to investigate the cutaneous tolerance of detergent products in the past. As the sensitivity of newly designed biometric methods is steadily improving, the trend towards more realistic test conditions should be encouraged. A hand immersion test under laboratory-controlled usage conditions is presently described, fulfilling such principles. Panelists soaked their hands in 2 different hand dishwashing liquids, 2x daily for 10 min each (with successive in-solution/out-of-solution cycles) for 4 consecutive days. Products were at usual dilution for dishwashing liquids and were randomized between the dominant and non-dominant hands of panelists. Visual scoring of erythema and dryness developing on the whole hands (scoring scales including interdigital areas and joints) during the week did not allow discrimination between the 2 products. However the dominant hands were significantly more susceptible to alterations than the non-dominant hands, regardless of product attribution. In contrast, skin electrical measurements (Corneometer CM800 and Skicon 200) on the dorsum of the hands (muscle mass between thumb and index) and squamometry analysis of tape stripping (harvested from the same site) yielded significant differences between the 2 products. In conclusion, a hand immersion test under realistic conditions has been described, which discriminates between products when sensitive assessment methods are used to explore skin sites partially protected from daily-life skin aggressions.

Squamometry: a tool to move from exaggerated to more and more realistic application conditions for comparing the skin compatibility of surfactant-based products.

Squamometry consists of sampling the most superficial layers of the stratum corneum by means of a sticky tape firmly pressed onto the skin. Harvested cells are stained and the intensity of staining is related to the level of skin surface alterations caused by surfactant-based products. This method is extremely sensitive and the current study demonstrates that, thanks to squamometry, product mildness can now be compared without causing skin irritation due to exaggerated application conditions. In a 15 minute patch test, squamometry assessments ranked a series of surfactants as expected from their known irritation potential, without causing clinical signs of irritation. Similarly, the counter-irritant effect of amphoteric and nonionic surfactants on the irritation potential of anionic surfactants was evidenced. In a 30 minute patch test, shampoos were ranked by squamometry as they were in a classical Soap Chamber Test (48 hours of application). Finally, four hand dishwashing liquids were tested for one week by consumers according to a procedure similar to normal usage of the products, and were classified by squamometry as they were in a previous Soap Chamber Test. In conclusion, this study suggests that squamometry is able to predict the skin compatibility of surfactant-based products even after very short and realistic application times to volunteers' skin. Providing further validation, this technique could allow a move to test conditions much closer to the normal usage procedure of the products, to design test protocols much more respectful of panelists' skin condition, and to get information on product tolerance very quickly.

Sensitive skin at menopause; dew point and electrometric properties of the stratum corneum.

OBJECTIVE: A number of menopausal women experience skin sensitive to various environmental threats. METHOD: Two panels of 15 menopausal women on or without HRT were compared. We studied the response of their stratum corneum to variations in environmental humidity, either in air or in response to an emollient. Environment dew point and electrometric measurements on the skin were recorded to search for correlations. RESULTS: Data show that the baseline stratum corneum hydration is influenced by the dew point. HRT improves the barrier function of the skin. The use of emollient further extends the improvement in the functional properties of skin in menopausal women. CONCLUSION: Both HRT and an emollient can counteract in part some of the deleterious effects of cold and dry weather.

Open application assay in investigation of subclinical irritant dermatitis induced by sodium lauryl sulfate (SLS) in man: advantage of squamometry.

BACKGROUND/AIMS: After a single occlusive application (24 h patch test), SLS can cause irritation, dryness, and tightness. In typical use, clinical surfactant exposure is usually brief, of open application, and cumulative. The open application model becomes relevant when phenomena, such as dryness and subclinical, i.e., non-visible, irritation are induced. METHODS: Exaggerated hand wash was performed in a total of 21 healthy individuals. Signs of skin irritation were scored, and skin reactions were measured using various bioengineering techniques. RESULTS: These studies demonstrate that an exaggerated hand wash model permits exploration of sub-clinical irritation. CONCLUSIONS: Squamometry proved to be a sensitive, complementary method to detect surfactant-induced, sub-clinical skin alterations.

Comparison of in vitro predictive tests for irritation induced by anionic surfactants.

Skin compatibility of anionic surfactants may often but not always be predicted by in vitro tests. For instance, the correlation between in vivo and in vitro data is classically hampered in the presence of magnesium. This ion is known to interfere with in vitro skin irritation predictive tests based on protein denaturation. This study was conducted to compare a recently introduced assay, corneosurfametry, with other in vitro tests including the pH-rise of bovine serum albumin, collagen swelling, and zein solubilization tests. Corneosurfametry entails collection of cyanoacrylate skin surface strippings and short contact time with surfactants, followed by staining samples with toluidine blue and basic fuchsin dyes. Measurements are made by reflectance colorimetry. Data show that irritation potentials predicted by corneosurfametry agree with those obtained by established in vivo and in vitro irritation tests. Moreover, corneosurfametry data are not artificially lowered by addition of magnesium in surfactant solutions. In conclusion, corneosurfametry should be viewed as one of the realistic predictive tests for surfactant irritancy.

Skin irritancy classification of body cleansing products: Comparison of two test methodologies.

BACKGROUND/AIMS: Mildness of skin cleansing products is often claimed although difficult to substantiate. Both the society and the producer share a common interest that cleansing products are safe in use and that valid methods are used for premarketing evaluation of new products. The object of the present study was to evaluate methodological aspects when three products were compared using two different test systems to characterize their irritant properties. METHODS: A modified soap chamber test (M-SCT) and an iterative short-term patch test (IPT) were performed. Eight healthy female volunteers aged 18 to 55 selected as having responsive skin were studied. Colorimetry and measurement of transepider-mal water loss was employed. A soap, a synthetic detergent bar and a facial cleanser were studied with deionized water as a reference. RESULTS: The IPT appeared more sensitive than the M-SCT for the detection and discrimination of irritation. The techniques allowed the ranking of the irritant properties of the products relative to water, which showed low values in both systems. CONCLUSION: Ranking of irritant properties of cleansing products was possible even in a limited number of individuals. Iterative short-term patch test was more sensitive than a modified soap chamber test.

Corneometiy measurements to evaluate skin dryness in the modified soap chamber test.

BACKGROUND/AIMS: Patch test procedures have been developed to compare the irritation potential of surfactant-based products. Skin changes due to product application are usually assessed visually by a trained evaluator using standard scoring scales or instrumentally. This study has been carried out to optimize the assessment of skin dryness in the Modified Soap Chamber Test both by visual scoring and Comeometer measurement, with transepidermal water loss as an additional measure. METHODS: Products were applied, under occlusion, to the skin, for 2 successive periods of 24 and 21 h; skin reactions were evaluated 3 h after removal of each series of patches, and followed up to 7 days after patches had been removed. RESULTS: Skin dryness progressively develops after patch removal, and reaches a maximum 3 to 5 days later. Capacitance measurements correlate the best with visual scoring of dryness when waiting 5 days after patch removal before assessment. CONCLUSIONS: Comeometer is an useful instrument to quantify observed dryness only when transepidermal water loss has recovered a value close to its baseline value. For both visual and instrumental assessments of skin dryness, waiting 3 to 5 days after patch removal in the Modified Soap Chamber Test will provide the most valuable results.