Heat Shock Lipolysis: Radiofrequency Combined with Cryolipolysis for the Reduction of Localized Subcutaneous Fat.

Introduction. Noninvasive procedures such as cryolipolysis, noncontact selective radiofrequency (RF), and laser selective fat heating have been shown to be safe and effective for the reduction of localized subcutaneous fat. Material and Methods. In this retrospective study, we describe the safety and efficacy of combining RF with cryolipolysis for localized unwanted fat after one single session. 69 patients, 61 females, and 8 males for a total of 75 treatments were included in this study. All patients underwent RF prior to and following cryolipolysis. Pictures (n = 24), taken before and after treatment, were used to clinically assess the physician Global Aesthetic Improvement Scale (PhGAIS). In parallel, patients were asked to subjectively evaluate the efficacy of the treatment using the same scale (PaGIAS). RESULTS: PhGIAS showed an improvement in 18 patients (73.46%), 5 (22.44%) were unchanged, and 1 (4.08%) worsened their appearance after treatment. The mean PaGIAS scored as "good improvement." CONCLUSION: In conclusion, combining RF with cryolipolysis in one single session is safe and effective.

Infant epidermal skin physiology: adaptation after birth.

BACKGROUND: Functional and structural skin adaptation is a dynamic process which starts immediately after birth in humans and in mammalian skin in general. This adjustment to the extrauterine dry environment is accomplished in the first year of postnatal life of humans. OBJECTIVES: To assess the dynamic changes in vivo after birth in the molecular composition and skin physiology parameters compared with older children and adults. METHODS: The molecular composition of the stratum corneum (SC) and the water profile were investigated noninvasively by in vivo Raman confocal microscopy as a function of depth. Functional parameters including transepidermal water loss (characterizing epidermal permeability barrier), capacitance (as an indirect parameter for SC hydration) and skin surface pH were assessed noninvasively. The measurements were performed in 108 subjects divided into six age groups: full-term newborns (1-15 days), babies aged 5-6 weeks, babies aged 6±1 months, children aged 1-2 years, children aged 4-5 years and adults aged 20-35 years. RESULTS: We showed that skin acidification is still under development during the first weeks of life. While the basal epidermal barrier is competent immediately after birth, the SC is less hydrated in the first 2 weeks of postnatal life. Similar continuous decreasing water content towards the surface for all age groups was observed, whereas this gradient was lower for the newborns. Dynamic changes in the amounts of the natural moisturizing factor constituents were revealed in the period of infancy. CONCLUSIONS: We demonstrated the relation of formation of an acidic pH as well as underlying mechanisms in the induction of a fully hydrated SC over the first weeks of human life as a dynamic functional adaptation.

LEKTI-1 in sickness and in health.

The stratum corneum (SC) is a biosensor that mediates responses to a variety of exogenous insults through various signalling mechanisms, including the activation of SC serine proteases (SP) kallikrein cascade. The SPINK5 gene encodes an SP inhibitor, the lympho-epithelial-Kazal-type-1 inhibitor (LEKTI-1), which in turn will buffer the excess of SP cascade initiation, key in the maintenance of permeability barrier homeostasis. We demonstrate that LEKTI processing can occur within the SC after secretion from stratum granulosum keratinocytes at least partially by klk7, an SC-specific chymotryptic SP. Unlike the recently described LEKTI-2, neither recombinant full-length LEKTI-1 nor recombinant LEKTI-1 fragments exhibit antimicrobial activity. Finally, we discuss the pathophysiological implications of LEKTI-1 in skin biology as well as its contribution to the pathogenesis of Netherton Syndrome and its potential involvement in atopic dermatitis.

Seasonal effects on the nasolabial skin condition.

In the present work, nasolabial skin condition and the influence of seasonal changes during autumn and winter were studied in 16 healthy female volunteers. Apart from visual scoring of erythema and skin scaliness, transepidermal water loss (TEWL), skin hydration, apparent skin pH, skin colour and skin desquamation were biophysically measured. The study results showed that nasolabial TEWL was significantly higher during wintertime than in autumn. Also skin colour measurements and squamometry scorings revealed higher values, indicating a more reddish and scaly nasolabial skin during winter compared to autumn. Results from tape stripping and skin surface lipid analysis by high-performance thin-layer chromatography demonstrated significant differences for triglycerides and cholesterol esters, indicating a functionally inferior hydrolipidic layer during the winter season.

Epidermal ceramidase activity regulates epidermal desquamation via stratum corneum acidification.

The acidic pH of the outer surface of the mammalian skin plays several important roles in the epidermal barrier function. The 2 endogenous pathways that are currently known to elicit this acidic pH are the generation of free fatty acids from phospholipids and the exchange of protons for sodium ions by non-energy-dependent sodium-proton exchangers. In this study, we propose a third endogenous pathway, i.e. epidermal ceramidase activity, generating free fatty acids from ceramides. By topical application of N-oleylethanolamine, a well-known ceramidase inhibitor, we could demonstrate a significant increase in the stratum corneum pH and a corresponding decrease in the epidermal free fatty acid content. Moreover, we could show that the resulting change in the apparent skin pH also provoked a delay in early barrier recovery and an increased epidermal desquamation, corresponding to earlier observations made for the already known endogenous mechanisms.

The two compartment model of the stratum corneum: biochemical aspects and pathophysiological implications.

"La raison d'être" of the epidermis, as beautifully portrayed by Kathy Madison in The Journal of Investigative Dermatology (2003;121:231-41), describes the primary function of the skin: The terminal differentiation of an initially multipotent stem cell produces a protective, semi-permeable SC that permits terrestrial life. The permeability barrier function of the SC is provided by lipid bilayers lamellae surrounding anucleated apoptotic corneocytes. This structure has been described by Peter Elias as the "bricks and mortar" model where the bricks are the cornecytes and the mortar refers to the adjoining lipids. How important is the barrier to the skin? Certain genetic defects are characterized by profound barrier abnormaities due to alterations in either stratum corneum lipid metabolism or protein components of the corneocytes, producing ichthyotic genodermatosis. In this review, the mechanisms that drive barrier formation are summarized and this in the light of our recent scientific findings and publications in the domain of epidermal structure and function.

Extracellular pH Controls NHE1 expression in epidermis and keratinocytes: implications for barrier repair.

We have previously shown that the Na+/H+ antiporter (NHE1) is an essential endogenous pathway responsible for stratum corneum (SC) acidification. Since the epidermis must re-establish its epidermal barrier after acute barrier perturbations, we asked whether the NHE1 was, in turn, regulated by changes in barrier status. We found that in vivo epidermal NHE1 expression was upregulated within hours of barrier disruption. We next asked whether NHE1 was regulated by barrier status per se, or by the SC alkalinization that accompanies barrier perturbation. NHE1 was upregulated by alkalinizing SC pH, whereas this antiporter was downregulated by acidifying SC pH, independent of changes in barrier status. Moreover, acidifying SC pH overrode the effects of barrier break in regulating NHE1 expression, suggesting that SC alkalinization is the major stimulus for increased NHE1 expression. Finally, we confirmed that the keratinocyte NHE1 antiporter is regulated by extracellular pH independent of barrier status, by demonstrating that NHE1 was upregulated in cultured keratinocytes exposed to pH 8.3 medium and downregulated in cultured keratinocytes exposed to pH 6.3 medium. These data suggest that the keratinocyte NHE1 is regulated by extracellular pH. SC barrier break also upregulates NHE1 expression, but this response seems to be mediated by concomitant changes in SC pH.

The prevalence of positive reactions in the atopy patch test with aeroallergens and food allergens in subjects with atopic eczema: a European multicenter study.

BACKGROUND: The atopy patch test (APT) was proposed to evaluate IgE-mediated sensitizations in patients with atopic eczema (AE). OBJECTIVE: The prevalence and agreement with clinical history and specific IgE (sIgE) of positive APT reactions was investigated in six European countries using a standardized method. METHODS: A total of 314 patients with AE in remission were tested in 12 study centers on clinically uninvolved, non-abraded back skin with 200 index of reactivity (IR)/g of house dust mite Dermatophagoides pteronyssinus, cat dander, grass, and birch pollen allergen extracts with defined major allergen contents in petrolatum. Extracts of egg white, celery and wheat flour with defined protein content were also patch tested. APT values were evaluated at 24, 48, and 72 h according to the European Task Force on Atopic Dermatitis (ETFAD) guidelines. In addition, skin-prick test (SPT) and sIgE and a detailed history on allergen-induced eczema flares were obtained. RESULTS: Previous eczema flares, after contact with specific allergens, were reported in 1% (celery) to 34% (D. pteronyssinus) of patients. The frequency of clear-cut positive APT reactions ranged from 39% with D. pteronyssinus to 9% with celery. All ETFAD intensities occured after 48 and 72 h. Positive SPT (16-57%) and elevated sIgE (19-59%) results were more frequent. Clear-cut positive APT with all SPT and sIgE testing negative was seen in 7% of the patients, whereas a positive APT without SPT or sIgE for the respective allergen was seen in 17% of the patients. APT, SPT and sIgE results showed significant agreement with history for grass pollen and egg white (two-sided Pr > /Z/ < or = 0.01). In addition, SPT and sIgE showed significant agreement with history for the other aeroallergens. With regard to clinical history, the APT had a higher specificity (64-91% depending on the allergen) than SPT (50-85%) or sIgE (52-85%). Positive APT were associated with longer duration of eczema flares and showed regional differences. In 10 non-atopic controls, no positive APT reaction was seen. CONCLUSION: Aeroallergens and food allergens are able to elicit eczematous skin reactions after epicutaneous application. As no gold standard for aeroallergen provocation in AE exists, the relevance of aeroallergens for AE flares may be evaluated by APT in addition to SPT and sIgE. The data may contribute to the international standardization of the APT.

Efficacy of topical corticosteroids in nickel-induced contact allergy.

In this study we used the nickel contact allergy patch (CAP) test to investigate the effect of topical corticosteroids on allergic contact dermatitis (ACD). On day 1, three CAP tests were applied for 48 h on the forearms of 20 female volunteers with a known nickel ACD. CAP of the right forearm contained 5% nickel, and of the left forearm physiological saline. Clinical scoring, transepidermal water loss and skin hydration were measured on day 1 before CAP application, on day 4 (0, 2 and 6 h) after ACD and from days 5 to 8 (0 h). A topical corticosteroid and its vehicle were applied twice daily starting from day 4 on two ACD sites. Transepidermal water loss values were significantly decreased on the topical-corticosteroid-treated sites in the early phase of ACD (day 4, 6 h after the first application) while clinical efficacy showed significant improvement on days 7 and 8. The vehicle was found to improve skin hydration only on day 8. In conclusion the topical corticosteroid improved the skin barrier function in the early inflammatory phase of ACD (day 4, 6 h). The lack of improvement in transepidermal water loss in the later phase of ACD might be accounted for by the secondary effects of the corticosteroid on proliferation and differentiation of keratinocytes.

Squamometry as a screening method for the evaluation of hydrating products.

BACKGROUND/AIMS: Squamometry is a combination of sampling corneocytes by adhesive coated discs followed by colour measurements after staining the cells. In this study, the correlation between stratum corneum (SC) hydration and scaling was investigated using capacitance measurements and squamometry, respectively. METHODS: Stratum corneum hydration and assessment of barrier function by transepidermal water loss (TEWL) measurements were carried out on different sites of left and right volar forearm skin of female volunteers (n = 13; 24 +/- 3 years). D-Squame samples were taken on the same test spots. RESULTS: Visual evaluation of the coloured samples by light microscopy and the development of a four-point-scale scoring system was found to be necessary to detect and minimise overestimation of chroma C* values. Capacitance measurements revealed neither significant differences between corresponding sites on left and right forearms no between different skin areas on the same forearm. Squamometric measurements, on the contrary, did not show any symmetry between corresponding test sites on both forearms or between different sites on one forearm. No correlation could be found between squamometric measurements and SC hydration values obtained at the same test sites. No skin barrier function impairment lays at the origin of this observation since TEWL values were found to be similar at all test sites in comparison to control skin. In a randomised single blind study, hydration and TEWL showed a significant improvement of 25% and 15%, respectively, after a 14-day application period of a moisturising cream. Although visual scoring of the coloured samples of both treated and untreated test spots revealed a good correlation with chroma C* values, the quantitative results found with squamometry were very doubtful. CONCLUSION: Squamometry with visual scoring can be proposed as a screening technique for SC hydration rather than a quantitative method to appreciate skin moisturisation.

Combination therapy improves the recovery of the skin barrier function: an experimental model using a contact allergy patch test combined with TEWL measurements.

BACKGROUND: Nickel (Ni) allergic contact dermatitis (ACD) alters the skin barrier. OBJECTIVE: Our aim was to compare the efficacy of combination therapies on ACD, using a topical corticosteroid and a corneotherapy agent (barrier cream), with that of a single therapy with corticosteroids. METHODS: On day 1, 3 Ni test patches were applied on each forearm of 14 Ni-patch-test-positive females. Four contained 5% Ni and 2 physiological saline. Either topical corticosteroid or barrier cream were matched with the combination of both products on 3 of the 4 Ni ACD. The fourth was not treated. Clinical scoring, transepidermal water loss (TEWL) and stratum corneum (SC) capacitance were measured before (day 1) and after (days 4-8) ACD. RESULTS: The combination therapy showed a significant decrease in TEWL values and an increase in SC capacitance. CONCLUSION: Combining a topical corticosteroid with corneotherapy agents prevents the delay in the healing process of skin barrier disruption due to ACD.

Beneficial effects of a skin tolerance-tested moisturizing cream on the barrier function in experimentally-elicited irritant and allergic contact dermatitis.

In experimentally-induced irritant (ICD) and allergic (ACD) contact dermatitis, an oil-in-water (o/w) cream was applied to investigate its effects on a disturbed barrier function compared to untreated physiological barrier repair. Transepidermal water loss (TEWL) measurements were performed. Before the start of the experiments, the skin tolerance of the cream was examined, revealing the non-irritating characteristics of the ingredients and the absence of any contact allergic patch test reaction. In the ICD study, sodium lauryl sulfate (SLS) patches were applied to the forearms of young female volunteers. Consequently, it was observed that repeated cream application (14 days, 2x/day) significantly improved the TEWL of SLS-damaged skin, leading to a complete recovery on day 15. In the ACD study, disruption of skin barrier function was obtained by a nickel-mediated contact allergy patch (CAP) test. The cream was then applied 2x/day for 4 consecutive days. Assessment of TEWL clearly showed that recovery of the disrupted skin significantly improved after cream application in comparison to untreated barrier repair.