A phase I, randomized, double-blind study to assess the safety, tolerability and efficacy of the topical RORC2 inverse agonist PF-06763809 in participants with mild-to-moderate plaque psoriasis.

BACKGROUND: Transcription factor retinoic acid-related orphan receptor 2 (RORC2/RORγT) mediates interleukin (IL)-17A and IL-17F expression. IL-17A plays a central role in the pathogenesis of several inflammatory disorders, including psoriasis. The RORC2 inhibitor PF-06763809 has been hypothesized to inhibit IL-17A production in T-helper 17 (Th17) cells, thereby reducing psoriasis symptoms. AIM: To assess the safety, tolerability and effect on skin infiltrate thickness of PF-06763809 in participants with mild/moderate chronic plaque psoriasis. METHODS: This was a randomized, double-blind, first-in-human study (trial registration: ClinicalTrials.gov NCT03469336). Participants received each of the following six treatments once daily for 18 days: three topical doses (2.3%, 0.8%, 0.23%) of PF-06763809, a vehicle and two active comparators (betamethasone and calcipotriol). Primary endpoints included change from baseline in psoriatic skin infiltrate thickness [echo-poor band (EPB) on ultrasonography] at Day 19, and safety. Change in psoriasis-associated gene expression (Day 19), evaluated by real-time reverse transcription PCR of skin biopsies, was an exploratory endpoint. RESULTS: In total, 17 participants completed the study. Change from baseline in the EPB on Day 19 for all three doses of PF-06763809 was not significantly different from that of vehicle (P > 0.05). A significant reduction in EPB from baseline was observed with betamethasone on Day 19 relative to all other treatments (P < 0.0001). Treatment-related adverse events were mild/moderate. There were no significant differences in gene expression on Day 19 between vehicle and PF-06763809-treated skin lesions. CONCLUSION: Using a psoriasis plaque test design, PF-06763809 was found to be well tolerated with an acceptable safety profile in participants with psoriasis, but without reduction in skin infiltrate thickness or disease biomarkers.

Adapting epicutaneous patch testing protocols to assess immediate-type skin reactions.

OBJECTIVE: During the development of cosmetic formulations, in vitro and in vivo methods are essential tools used to reliably assess the skin irritation potential of a product or ingredient. Epicutaneous patch testing (single and/or multiple application protocols) has long been used as an initial in vivo method to screen for possible skin irritation properties of a substance or formulation. To confirm the mildness and dermatological and/or consumer acceptance of a product, use tests are often subsequently conducted. A study was therefore initiated to see how well patch test results correlate with use tests with respect to irritation elicited by skincare (leave-on) products. METHODS/RESULTS: A number of different cosmetic formulations were assessed in both tests. Although the patch test results did not indicate substantial irritation potentials, immediate-type reactions (stinging and redness) were observed in some volunteers which disappeared within approx. 1 h. Although transient, these reactions suggested that consumer acceptance would probably be low and the studies were discontinued. Immediate-type reactions are rare but have been described for some substances used in cosmetics. These unexpected results were nevertheless intriguing and prompted the start of a journey to see if patch test protocols could be modified to assess these reactions. An occlusive short-term patch test protocol with an application period of 20 min was developed. Successful identification of the spontaneous reactions became possible. Furthermore, there was a correlation between the intensity of reactions observed in the short-term patch test and those observed in the controlled in-use studies. Short-term patch testing using the developed protocol can therefore reliably be used as a screening method, for example in the development and optimization of cosmetic formulations containing ingredients that could cause spontaneous reactions, for instance of non-immunological contact urticaria type. CONCLUSION: The lessons learned from this studies indicate that simple modifications of existing test protocols can lead to important insights into skin reactions. These modifications can then be used to create further building blocks in the development and optimization of test strategies for cosmetic formulations which offer reliable study designs for possible reactions product developers may encounter.

OBJECTIF: Lors du développement de formulations cosmétiques, les méthodes in vitro et in vivo sont des outils essentiels utilisés pour évaluer de manière fiable le potentiel d'irritation cutanée d'un produit ou d'un ingrédient. Le test épicutané (protocoles d'application uniques et / ou multiples) est utilisé depuis longtemps comme méthode initiale in vivo pour dépister les éventuelles propriétés d'irritation cutanée d'une substance ou d'une formulation. Afin de confirmer la douceur et l'acceptation dermatologique et / ou consommateur d'un produit, des tests d'usage sont souvent effectués ultérieurement. Une étude a donc été initiée pour voir dans quelle mesure les résultats des tests épicutanés correspondent aux tests d'usage en ce qui concerne l'irritation provoquée par les produits de soin (sans rinçage). MÉTHODES/RÉSULTATS: Un certain nombre de formulations cosmétiques différentes ont été évaluées dans les deux tests. Bien que les résultats du test épicutané n'indiquent pas de potentiels d'irritation substantiels, des réactions de type immédiat (picotements et rougeurs) ont été observées chez certains volontaires. Celles-ci ont disparu en à peu près 1 heure. Bien que transitoires, ces réactions de type 5 suggéraient que l'acceptation du consommateur serait probablement faible et les études ont été interrompues. Les réactions de type immédiat 6 sont rares mais ont été évoquées en relation avec certaines substances utilisées en cosmétique. Ces résultats inattendus étaient néanmoins intrigants et ont incité le lancement d'un processus pour voir si les protocoles de test épicutané pouvaient être modifiés pour évaluer ces réactions. Un protocole de test épicutané à court terme occlusif avec une période d'application de 20 min a été développé, permettant l'identification réussie des réactions spontanées. Il a été de plus constate une corrélation entre l'intensité des réactions observées dans le test épicutané à court terme et celles observées dans les test d'usage contrôlés. Le test épicutané à court terme utilisant le protocole développé peut donc être utilisé de manière fiable comme méthode de dépistage, par exemple dans le développement et l'optimisation de formulations cosmétiques contenant des ingrédients qui pourraient provoquer des réactions spontanées, par exemple de type urticaire de contact non immunologique. CONCLUSION: Les leçons tirées de ces études indiquent que de simples modifications des protocoles de test existants peuvent révéler des informations importantes sur les réactions cutanées. Ces modifications peuvent ensuite être utilisées pour créer d'autres blocs de construction dans le développement et l'optimisation de stratégies de test pour des formulations cosmétiques qui offrent des conceptions d'études fiables pour les réactions possibles que les développeurs de produits peuvent rencontrer.

A phase I randomized trial to assess the effect on skin infiltrate thickness and tolerability of topical phosphodiesterase inhibitors in the treatment of psoriasis vulgaris using a modified psoriasis plaque test.

BACKGROUND: Oral phosphodiesterase (PDE)4 inhibitors have shown efficacy in chronic obstructive pulmonary disease and psoriasis. OBJECTIVES: To assess the effectiveness, local safety and tolerability, and systemic pharmacokinetics of two topical PDE4 inhibitors, roflumilast and TAK-084, in plaque psoriasis. METHODS: An intraindividual comparison of six topical products was made in 15 patients aged 18-65 years with stable chronic plaque psoriasis in an investigator-blinded, within-subject randomized study. The products evaluated were calcipotriol 0·005% cream; betamethasone valerate 0·1% (both in their marketed formulations); investigational cream formulations of roflumilast 0·5% and TAK-084 0·5% and 5%; and a vehicle cream formulation as a control. Each treatment was applied daily to different test sites located on psoriasis plaques for 3 weeks. RESULTS: The primary end point of (mean) change from baseline in skin infiltrate thickness after 3 weeks of treatment showed statistically significant improvements for all treatments: betamethasone valerate cream (-286·9 µm), the selective PDE4 inhibitors roflumilast 0·5% (-237·1 µm) and TAK-084 (0·5% cream, -153·6 µm; 5% cream, -216·7 µm) and calcipotriol 0·005% (-187·7 µm) when compared with vehicle cream control (all P < 0·001). Both the TAK-084 5% and roflumilast 0·5% formulations performed well overall compared with the potent corticosteroid, betamethasone, and were ranked better than the vitamin D analogue calcipotriol. All adverse events were mild or moderate and none was serious. CONCLUSIONS: Topical treatment with cream formulations of the PDE4 inhibitors roflumilast and TAK-084 reduced inflammation, measured as a change in skin infiltrate thickness, and reduced psoriasis severity. Corticosteroid treatments have known systemic and cutaneous side-effects; PDE4 inhibitors could offer an alternative to these and deserve further study.

Efficacy of a tyrothricin-containing wound gel in an abrasive wound model for superficial wounds.

BACKGROUND: Topical preparations are a common treatment for superficial acute wounds, which at the least do not interfere with healing and ideally result in enhanced wound healing irrespective of microbial colonization. OBJECTIVE: To examine the effects of a topical antimicrobial gel and its vehicle on the wound healing of standardized, superficial abrasions. METHODS: Thirty-three healthy volunteers were enrolled in a double-blinded, randomized, intraindividual comparison study. Three standardized, superficial abrasions were induced on their forearms. A tyrothricin 0.1% gel (Tyrosur® gel; Engelhard Arzneimittel GmbH & Co. KG, Niederdorfelden, Germany) and its vehicle were randomly applied to two of the test areas, and one lesion remained untreated. RESULTS: A significant improvement of wound healing was seen with both tyrothricin 0.1% gel and its corresponding vehicle in the clinical assessment. The mean area under the curve (AUC) of wound healing scores was the same for both preparations and the mean reepithelization scores were comparable at all test points over the entire 12 days. A lower mean AUC representing less reepithelization was found for the untreated test fields. CONCLUSION: The use of tyrothricin 0.1% gel and its corresponding vehicle resulted in statistically significant improved wound healing with an earlier onset of healing in particular. Based on these results obtained using an abrasive wound model, it can be concluded that the addition of tyrothricin 0.1% to the gel vehicle did not interfere with the improved wound healing seen with the vehicle alone.

Tandem repeated irritation in aged skin induces distinct barrier perturbation and cytokine profile in vivo.

BACKGROUND: The barrier perturbation pattern and molecular markers of inflammation upon tandem repeated irritation in chronologically aged skin have not been previously studied. OBJECTIVES: We aimed to investigate the barrier impairment kinetic and in vivo cytokine profile following sequential irritation with sodium lauryl sulfate (SLS) and undiluted toluene (Tol) in aged compared with young skin. METHODS: Four fields on the volar forearm of healthy aged and young volunteers (median age, respectively, 63.9 and 32.6 years) were sequentially exposed to 0.5% SLS and undiluted toluene in a controlled tandem repeated irritation test; an adjacent nontreated field served as control. The permeability barrier function was monitored by repeated measurements of transepidermal water loss (TEWL), capacitance and erythema every 24 h up to 96 h. The stratum corneum cytokines were harvested by sequential tape stripping and quantified by multiplex bead array and enzyme-linked immunosorbent assay. RESULTS: Compared with young skin, aged skin was characterized by delayed and/or less pronounced alterations in the visual irritation score, TEWL, chromametry a*-value and capacitance, assessed by the respective Δ-values for each parameter and monitoring time point. In both groups, exposure to SLS/SLS, SLS/Tol and Tol/SLS resulted in decreased interleukin (IL)-1α levels, whereas the application of Tol/Tol induced an increase in IL-1α. Furthermore, decreased IL-1 receptor antagonist (IL-1RA) levels and a lower IL-1RA/IL-1α ratio were found following repeated exposure to the irritants. CONCLUSIONS: Our results provide evidence for selective alterations in the cytokine profile and distinct barrier impairment kinetic following tandem repeated irritation with SLS and Tol in aged compared with young skin in vivo.

Bioavailability, antipsoriatic efficacy and tolerability of a new light cream with mometasone furoate 0.1%.

Mometasone furoate, a potent glucocorticoid (class III) with a favorable benefit/risk ratio, has emerged as a standard medication for the treatment of inflammatory skin disorders. The purpose of the investigation presented here was to determine the noninferiority of a topical mometasone formulation, a light cream (O/W 60/40 emulsion) with mometasone furoate 0.1% (water content of 33%) versus marketed comparators. Using the vasoconstrictor assay, a strong blanching effect of the new cream (called Mometasone cream) comparable to that of a mometasone comparator, a fatty cream with mometasone furoate 0.1%, could be demonstrated. Thus, the topical bioavailability of the active ingredient mometasone furoate (0.1%) was regarded to be similar for Mometasone cream and the mometasone comparator. Using the psoriasis plaque test, a strong antipsoriatic effect comparable to that of the mometasone comparator was found for Mometasone cream after 12 days of occlusive treatment. A nearly identical reduction in the mean infiltrate thickness and similar mean AUC values were noted with both formulations confirmed by clinical assessment data. The noninferiority of Mometasone cream to its active comparator with respect to the AUC of change to baseline in infiltrate thickness was demonstrated. Both medications were well tolerated. Overall, Mometasone cream and the mometasone comparator showed similar efficacy and tolerability. Mometasone cream, in addition to its high potency and good tolerability, provides the properties of a light cream, which might make this new medication particularly suitable for application on acutely inflamed and sensitive skin.

Efficacy of a new mouthrinse formulation on the reduction of oral malodour in vivo. A randomized, double-blind, placebo-controlled, 3 week clinical study.

The present study was conducted to assess the efficacy of a new mouthrinse formulation in reducing oral malodour compared to that of commercially available products containing chlorhexidine (CHX) and a negative control. 174 healthy volunteers, each with an organoleptic score of at least 2 and an H(2)S level as part of the volatile sulfur compounds (VSC) higher than 50 ppb, were divided into four groups. Participants were stratified according to their organoleptic ratings (OR). Group I: mouthrinse I (250 ppm F(-) from amine fluoride/stannous fluoride (ASF), 0.2% zinc lactate, oral malodour counteractives); group II: mouthrinse II (0.05% CHX, 0.05% cetylpyridinium chloride, 0.14% zinc lactate); group III: mouthrinse III (0.12% CHX); group IV: tap water. All groups were instructed to perform standardized oral hygiene measures and to apply the respective test rinse twice daily after tooth brushing. Malodour was assessed by organoleptic measurement and by VSC levels at baseline, day 1, day 7, day 14 and day 21 into the study. To evaluate discolouration of the teeth, the colour was assessed at baseline and final visit. The ASF mouthrinse showed superior efficacy as compared to the negative control. A significant reduction in OR and VSC readings was achieved after single application as well as after 7 and 21 days of continuous use. Between test groups I-III no statistically significant differences were found at any time point. There was also a trend towards fewer side effects caused by the ASF product compared to the products containing CHX. The newly developed mouthrinse product significantly reduces oral malodour in patients with increased values both in OR and in VSC.

Using a novel wound model to investigate the healing properties of products for superficial wounds.

OBJECTIVE: To establish a new wound model that can induce uniform abrasions and use it to assess the healing properties of a range of products commonly applied to these wounds. METHOD: Ten healthy volunteers were enrolled into an open-label, randomised, intra-individual comparison pilot study. Five standardised, superficial abrasions were induced on their forearms by repeatedly scrubbing the skin with a surgical brush until the first signs of uniform glistening and punctuate bleeding were observed. Three products that promote a moist wound environment (polyurethane, hydrocolloid, hydrogel) and two standard plasters were randomly allocated to the test areas. RESULTS: Evaluation of wound healing on days 2, 5, 8 and 14 +/- 1 showed best results for the polyurethane and hydrocolloid plasters. Visible re-epithelialisation was recorded on days 5 and 8. More than 50% of the wound area had closed. Video microscope images support these findings. The investigator and volunteers assessed cosmetic outcomes on day 31 +/- 2. Best results were obtained for the polyurethane and hydrocolloid products, which had high mean scores close to the maximum of 10. Histological examination of biopsies taken from the abrasions of two volunteers showed the dermis remained intact, making the model highly suitable for the study of superficial wounds. CONCLUSION: Uniform and identical standardised wounds created using an abrasive brush technique can be used to reliably detect differences in the performance of plasters intended for superficial wounds. In general, products that promote a moist wound environment produced better results than those that promote a dry wound environment, with an earlier onset of healing and better healing outcomes. Superficial cutaneous wounds treated with polyurethane or hydrocolloid products demonstrated superior rates of re-epithelialisation and overall cosmetic outcomes. DECLARATION OF INTEREST: This study was funded by Beiersdorf AG. Neither author has any interest in the sponsor's commercial activities.

Assessment of topical corticosteroid activity using the vasoconstriction assay in healthy volunteers.

OBJECTIVE AND DESIGN: The aim of the study was to evaluate the vasoconstrictive activity of four new galenic preparations of hydrocortisone and to compare it with concentration-equivalent reference preparations. The study comprised two study phases: the pilot study phase and the main study phase. During open, nonrandomized pilot study, the optimal administration period was tested. The main study was performed in a randomized, double-blind intraindividual comparative design. SUBJECTS: Twenty male and female volunteers with healthy skin who responded to topically applied clobetasol-17-propionate before entering the trial participated in this study. TREATMENT: All subjects received the same treatments. The test preparations new galenic formulation (NGF) hydrocortisone 0.25% cream, NGF hydrocortisone acetate 0.25% cream, NGF hydrocortisone 0.5% cream, and NGF hydrocortisone 1.0% cream were compared with the respective reference preparations Soventol hydrocortisone (hydrocortisone acetate 0.25%), Hydroderm HC 0.5% cream (hydrocortisone 0.5%), Hydrogalen cream (hydrocortisone 1.0%) and placebo (vehicle of test preparations). METHOD: The topical preparations were applied occlusively for 2 h (pilot study) or 24 h (main study) on outlined areas (5 x 5 cm with a distance of 3 cm) of both forearms (4 areas for each). Assessment of vasoconstriction was performed before treatment, and 0.5, 4, 6 and 24 h after treatment (observation period) using a subjective rating scale (OLSEN vasoconstriction score) and measuring the colorimetric parameter a* (redness) by use of the Chroma-Meter (Minolta company, Ahrensburg, Germany). RESULTS: A significant vasoconstriction (positive blanching effect) was measured by use of chromametry for test preparations hydrocortisone 0.25% cream, hydrocortisone 0.5% cream, hydrocortisone 1.0% cream and for the reference preparation Hydrogalen cream compared to placebo 30 min after the end of treatment. In contrast, the reference preparations Soventol hydrocortisone and Hydroderm HC 0.5% did not differ significantly from placebo 30 min after treatment. No statistically significant effect of all formulations was observed 4-24 h after treatment in comparison with placebo. CONCLUSIONS: The vasoconstrictive efficacy of test preparations was mostly stronger than the concentration-equivalent reference preparations. This effect was achieved by use of new galenics of test preparations resulting in enhanced skin penetration and improved efficiency. No unwanted side effects were observed during the course of the study despite increased efficacy of the topically applied test preparations.

Transepidermal water loss dynamics of human vulvar and thigh skin.

Refinement in procedures to assess skin surface water loss (SSWL) dynamics of the vulvar skin on a large sample of subjects (60) is described and compared to another semi-occluded skin site, the inner thigh. Vulvar SSWL significantly decreased over a 30-min period from 46.2 +/- 2.6 (SE) to 24.7 +/- 1.6 g m(-2) h (p < 0.001). The inner thigh, another semi-occluded region, showed no similar pattern for SSWL (6.2 +/- 0.3 to 6.6 +/- 0.5 g m(-2) h), and the values were significantly less than those for vulvar skin. There was no significant effect of age, body mass index or atopic status on vulvar SSWL.

Percutaneous penetration of topically applied melatonin in a cream and an alcoholic solution.

In a clinical study, the skin penetration properties of melatonin 0.01% in a cream and 0.01 and 0.03% in a solution were investigated by evaluation of the serum melatonin levels over a 24-hour time course in 15 healthy volunteers. Blood samples for melatonin measurements were taken at 9.00 a.m. before applying the test preparations and 1, 4, 8 and 24 h after application. The measurements were carried out by radioimmunoassay for melatonin. In 15 volunteers, the serum levels of melatonin before application of the topical preparations were between 0.6 and 15.9 pg/ml. After application of the 0.01% melatonin cream, there was a steady increase starting from 9.00 a.m. up to a mean serum value of 9.0 pg/ml at 9.00 a.m. the next day. The solution of 0.01% melatonin also showed an increase, starting from 5.00 p.m., up to a mean melatonin level of 12.7 pg/ml 24 h after application. The solution containing 0.03% melatonin resulted in elevated melatonin levels 1 and 8 h after application. The values were 18.1 and 19.0 pg/ml. The cumulative melatonin values for each preparation were 7.1, 8.6 and 15.7 pg/ml, respectively. This study shows that the strongly lipophilic substance melatonin is able to penetrate through the skin and leads to dose- and galenic-dependent melatonin levels in the blood. No increase of melatonin above the physiological range was observed.

Skin-conditioning products in occupational dermatology.

Moisturizers are frequently used in the prevention of occupational contact dermatitis. This review discusses their chemistry and mode of action. Methods to prove their preventive efficacy are presented. In addition to pharmacological efficacy, subjective factors that influence application of the products and compliance come into play. In conclusion, moisturizers are only one element of skin-disease prevention at the workplace that should be viewed as a complex, inter-dependent system. The efficacy of the complete, integrated system of occupational skin care has to be proven.

The atopy patch test -- reproducibility and comparison of different evaluation methods.

BACKGROUND: There is still a lack of standardization of the atopy patch test (APT) in test procedures and evaluation methods. Our aim was to examine the reproducibility of APT results and to compare visual evaluation to chromametry and laser Doppler imaging. METHODS: Fifty-two volunteers with atopic eczema/dermatitis syndrome (AEDS) were included. The APT was performed on tape-stripped and unstripped test fields on their backs using cat dander, house dust mite and grass pollen allergens from two different suppliers. Responders were re-tested 4-12 weeks later with the same allergens on their forearms. RESULTS: Using Allergopharma allergens, 14 (26.9%) volunteers showed one or more positive reactions. The reproducibility rate was 56.3%. The Erlangen atopy score in APT-positive and negative volunteers was 19 +/- 6 vs 15 +/- 6. The test agreement in volunteers tested with both allergens, from Allergopharma and Stallergènes, was poor. Correlation of the results between the three evaluation methods was significant (P < or = 0.001). CONCLUSIONS: The low reproducibility rate of APT results and the poor inter-test-agreement using allergens from different suppliers show that much work remains to make the APT a reliable tool in identifying relevant aeroallergens that lead to flare ups of AEDS. Compared to chromametry and laser Doppler imaging, visual scoring was superior in differentiation between irritative and allergic reactions.

Natural vegetable fats in the prevention of irritant contact dermatitis.

Chronic irritant contact dermatitis (ICD) is one of the most pressing problems in occupational medicine and is common in the food processing industry. To date, protective creams that fulfil the special requirements in the foodstuffs industry have not been available. Therefore, we studied the efficacy of pre-exposure application of natural vegetable fats in the prevention of experimentally induced ICD. A panel of 20 healthy volunteers was tested with a repetitive irritation test using sodium lauryl sulfate (SLS) as a standard irritant in a randomized study. Application sites were assessed clinically and by the use of bioengineering techniques (evaporimetry, chromametry, and corneometry). Rape seed and palm fats showed significant protective potential. Gas-chromatographic analysis revealed differences in the fatty acid composition of the vegetable. Higher content of linoleic acid and lower content of oleic acid was associated with beneficial effects. Our results are a new approach in the prevention of ICD and towards the development of new protective preparations for workplaces in the foodstuffs industry.

Case report. Monascus purpureus--a new fungus of allergologic relevance.

Anaphylactic reactions to food containing allergens in the consumption or preparation of food are well known. However, allergy in the preparation of sausages has rarely been described. In the present study a 26-year-old-butcher was investigated who had a severe anaphylactic reaction developing sneezing, rhinitis, conjunctivitis, generalised pruritus, followed by widespread urticaria, Quincke's oedema and dyspnoe after starting to prepare sausages containing red yield rice. Red yield rice is produced by the fungus Monascus purpureus. It was the first time that Monascus purpureus could be shown as allergic agent by means of prick-to-prick test, Cellular Antigen Stimulation Test (CAST) and different immunoblots.

[Clinical effectiveness and tolerance of climbazole containing dandruff shampoo in patients with seborrheic scalp eczema]. / Klinische Wirksamkeit und Verträglichkeit eines Climbazol-haltigen Antischuppen-Shampoos bei Patienten mit seborrhoischem Kopfhautekzem.

Pityrosporum ovale appears to play an important role in the pathogenesis of dandruff as a symptom of seborrheic dermatitis. Climbazole is an antimycotic agent with a high in vitro and in vivo efficacy against P. ovale. In the presented work we investigated the efficacy and safety of a climbazole 0.65% shampoo on seborrheic dermatitis of 30 volunteers. Subjects were diagnosed as having moderate to severe seborrheic dermatitis of the scalp. After a 1-week washout and a 4-week treatment the clinical evaluation showed a successful reduction of dandruff, skin redness and itching in 80% of the volunteers and a mild improvement in 20% of the volunteers. The cosmetic acceptability was very good by the majority. It is concluded that the formulation tested is effective in the treatment of moderate to severe dandruff.

Assessment of 'dry skin': current bioengineering methods and test designs.

Dry skin is a frequent problem in dermatology and a sign of dysfunction of the epidermis, especially of the stratum corneum as the morphological equivalent of the skin barrier. It may occur as an individual disposition or as the leading symptom of atopic dermatitis or ichthyosis. Besides the visual examination of the skin, various bioengineering methods have been developed to assess the different pathological and adaptive changes in the skin. In addition to the assessment of skin humidity, barrier function and desquamation, the quantification of skin surface topography and the mechanical properties of skin are suitable methods to characterize a dry skin condition. For clinical assessment of moisturizing products and emollients the parameters of investigation have to be defined and integrated in an adapted study design depending on the composition and content of the active agent in the test product. Newly developed cosmetic products have to be investigated for safety and efficacy. Modern bioengineering methods are suitable to fulfill these challenges.

Tandem application of sodium lauryl sulfate and n-propanol does not lead to enhancement of cumulative skin irritation.

Irritant contact dermatitis has a broad spectrum of clinical features and is a leading cause of occupational disease worldwide. It has been shown previously that a combination of chemically different irritants may cause an additive effect compared to single application of these substances. In this study, tandem application of sodium lauryl sulfate and n-propanol was investigated in 20 human volunteers using non-invasive bioengineering methods, such as measurement of transepidermal water loss and chromametry. N-propanol did not enhance cumulative skin irritation when used with sodium lauryl sulfate, as has been reported for toluene. As n-propanol is the active ingredient in many disinfectants, this is of particular interest regarding occupational skin irritation in health care workers.