New formulation of chemical peeling agent: 30% salicylic acid in polyethylene glycol. Absorption and distribution of 14C-salicylic acid in polyethylene glycol applied topically to skin of hairless mice

Salicylic acid is used in chemical peeling procedures. However, they have caused many side effects, even salicylism. To achieve a salicylic acid peeling that would be safer for topical use, we recently developed a new formulation consisting of 30% salicylic acid in polyethylene glycol (PEG) vehicle. In an extension of our previous research, we studied the absorption of 30% salicylic acid labeled with 14C in PEG vehicle applied topically to the intact and damaged skin of male hairless mice. An ointment containing 3 mg salicylic acid in 10 mg vehicle was applied to both groups. In animals with intact skin, 1 h after application the plasma concentration of radioactivity was 1665.1 ng eq/ml, significantly lower than the 21437.6 ng eq/ml observed in mice with damaged skin. Microautoradiograms of intact skin showed that the level of radioactivity in the cornified cell layer was similar at 6 h after application. However, in damaged skin, the overall level of radioactivity showed a decrease by 3 h after application. In the carcasses remaining after the treated intact and damaged skin had been removed, 0.09 and 11.38% of the applied radioactivity remained, respectively. These findings confirm that 30% salicylic acid in PEG vehicle is little absorbed through the intact skin of hairless mice, and suggest that salicylism related to absorption through the skin of quantities of topically applied salicylic acid is not likely to occur in humans with intact skin during chemical peeling with this preparation. This new preparation of 30% salicylic acid in PEG vehicle is believed to be safe for application as a chemical peeling agent.     

Comparative caustic and biological activity of trichloroacetic and glycolic acids on keratinocytes and fibroblasts in vitro

OBJECTIVES: Beside their causticity, the biological mechanism by which trichloroacetic acid (TCA) and glycolic acid (GA), two agents extensively used for chemical peeling, might act remains unknown. The purpose of this study was to examine in vitro the effect of TCA and GA on human keratinocytes and the influence of the released epithelial mediators on collagen and matrix metalloproteinases (MMPs) production by human dermal fibroblasts. METHOD: Cultured keratinocytes were treated by TCA and GA at 10 mg/ml brought to pH 3, 5 and 7, and the conditioned media neutralized to pH 7 were added to human normal skin fibroblasts. RESULTS: TCA was cytotoxic for keratinocytes at each tested pH. The conditioned medium depressed protein and collagen synthesis and the expression of MMPs when added to fibroblasts as did also TCA when added directly to fibroblasts. GA was not cytotoxic for keratinocytes at neutral pH and the conditioned medium obtained at each pH applied to fibroblasts did not alter protein, collagen nor MMPs production while causing an elevated secretion of IL-6. CONCLUSION: TCA exerts a toxic effect on keratinocytes and fibroblasts while GA does not alter the metabolism of fibroblasts but induces the secretion of IL-6.     

K6PC-5, a novel sphingosine kinase activator, improves long-term ultraviolet light-exposed aged murine skin

Sphingosine-1-phosphate (S1P), which is formed by phosphorylation of sphingosine through a process catalysed by sphingosine kinase (SK), is a multifunctional mediator of a variety of cellular responses including proliferation, differentiation, motility, and survival. K6PC-5, which was recently synthesized as a novel SK activator, is expected to increase S1P levels. Indeed studies have already demonstrated that K6PC-5 exhibits anti-aging effects on intrinsic aged murine skin by increasing fibroblasts, collagen synthesis, dermal thickness, and epidermal differentiation. However, photoaging and intrinsic aging have highly different clinical and histopathological properties. In this study, we developed a photoaged murine model by exposing mice that were 56 weeks old to ultraviolet (UV)B and UVA radiation for 8 weeks. We then investigated whether K6PC-5, as an SK activator, had anti-aging effects on photoaged murine skin in addition to its effects on intrinsic aged murine skin and determined the mechanism. K6PC-5 increased dermal collagen density in photoaged skin through increases in fibroblasts and collagen production. Photoaged murine skin treated with K6PC-5 showed an increase in stratum corneum (SC) integrity with increased corneodesmosome density and an improvement in barrier recovery rate. Matrix metalloproteinase 13 remained unchanged. These results indicate that topical application of K6PC-5 improves photoaged skin by improving skin barrier and increasing fibroblast count and function. In conclusion, K6PC-5, as an S1P activator, improves long-term UV-exposed aged skin as well as intrinsic aged skin.     

Chemical peeling by SA-PEG remodels photo-damaged skin: suppressing p53 expression and normalizing keratinocyte differentiation

Chemical peeling with salicylic acid in polyethylene glycol vehicle (SA-PEG), which specifically acts on the stratum corneum, suppresses the development of skin tumors in UVB-irradiated hairless mice. To elucidate the mechanism through which chemical peeling with SA-PEG suppresses skin tumor development, the effects of chemical peeling on photodamaged keratinocytes and cornified envelopes (CEs) were evaluated in vivo. Among UVB-irradiated hairless mice, the structural atypia and expression of p53 protein in keratinocytes induced by UVB irradiation were intensely suppressed in the SA-PEG-treated mice 28 days after the start of weekly SA-PEG treatments when compared to that in the control UVB-irradiated mice. Incomplete expression of filaggrin and loricrin in keratinocytes from the control mice was also improved in keratinocytes from the SA-PEG-treated mice. In photo-exposed human facial skin, immature CEs were replaced with mature CEs 4 weeks after treatment with SA-PEG. Restoration of photodamaged stratum corneum by treatment with SA-PEG, which may affect remodeling of the structural environment of the keratinocytes, involved the normalization of keratinocyte differentiation and suppression of skin tumor development. These results suggest that the stratum corneum plays a protective role against carcinogenesis, and provide a novel strategy for the prevention of photo-induced skin tumors.     

Medium-depth and deep chemical peels

Chemical peeling, also known as chemoexfoliation or dermapeeling, is performed to improve the skin's appearance as it reduces the wrinkles caused by aging and the features of photoaged skin. Although the best results are obtained with deep peels, the medium-depth peels allow to obtain excellent results without the dangerous side effects of deep peels. Medium-depth peelings are performed with trichloroacetic acid (TCA) at 35-50% alone or at 35% in combination with Jessner's solution, 70% glycolic acid, and solid CO(2). TCA must be applied with a cotton-tipped applicator or saturated gauze pads with smooth strokes. After application, a dry gauze pad must be used to blot the excess TCA from the skin. Postoperative care of 35% TCA peeling consists of cleansing during the following days. Habitually, medium-depth peelings with TCA alone or in combination have no complications. Sometimes, as a consequence of the patient's type of skin, the practitioner's lack of experience or other circumstances, complications such as hyper- or hypopigmentation, erythema, hypertrophiyc and keloid scars, infections, and milia may occur. Deep peeling with phenol has two modalities: unoccluded and occluded Baker's formula phenol. Unoccluded phenol peels is similar to the medium-depth peeling with Jessner's solution + TCA at 35%, but it has the disadvantage that it may produce cardiac and renal complications. This kind of peeling must be applied more slowly, and it is specific for the eyelids in full-face deep peeling. Afterpeel care is the same as that of medium-depth peeling. Complications of deep peelings can be cardiac arrhythmias, hypertrophic scars, infections, prolonged erythema, pigmentary changes, cutaneous atrophy, and exceptionally toxic shock syndrome.     

Peeling agents and irritants,unlike tretinoin,do not stimulate collagen synthesis in the photoaged hairless mouse

Tretinoin has been shown to stimulate the synthesis of collagen in photoaged human and hairless mouse skin. It has been suggested that this partial reversal of photodamage by tretinoin is a consequence of low-grade inflammation. The purpose of this study was to compare the effect of tretinoin with a number of irritants and peeling agents on collagen synthesis. Hairless mice were irradiated thrice weekly for 10 weeks with UVB. In the 10-week postirradiation period, the mice were treated topically five times per week with tretinoin (0.05%), glycolic acid (10%), benzalkonium chloride (1.0%), sodium lauryl sulfate (5%), croton oil (5%) and the water—propylene glycol vehicle. Microscopic measurements showed that the tretinoin-induced zone of new collagen was twice the depth of that induced by irritants or vehicle. The salt-soluble collagen content was determined by HPLC analysis of hydroxyproline levels. Type III procollagen was quantified by radioimmunoassay. Tretinoin-treated skin had increased amounts of collagen and type III procollagen whereas irritant- and peeling agent-treated skins were similar to vehicle-treated controls. Immunofluorescence studies were confirmatory. These results demonstrate that these agents, unlike tretinoin, do not have the capacity to enhance collagen synthesis. Therefore, it is likely that the effect of tretinoin does not depend upon irritation. This study was supported in part by Ortho Pharmaceutical Corp. Dermatology Division, Raritan, N.J., USA     

Dietary compound ellagic acid alleviates skin wrinkle and inflammation induced by UV‐B irradiation

Please cite this paper as: Dietary compound ellagic acid alleviates skin wrinkle and inflammation induced by UV‐B irradiation. Experimental Dermatology 2010; 19 : e182–e190. Abstract: Ellagic acid, a polyphenol compound present in berries and pomegranate, has received attention as an agent that may have potential bioactivities preventing chronic diseases. This study examined photoprotective effects of ellagic acid on collagen breakdown and inflammatory responses in UV (ultraviolet)‐B irradiated human skin cells and hairless mice. Ellagic acid attenuated the UV‐B‐induced toxicity of HaCaT keratinocytes and human dermal fibroblasts. Non‐toxic ellagic acid markedly prevented collagen degradation by blocking matrix metalloproteinase production in UV‐B‐exposed fibroblasts. Anti‐wrinkle activity of ellagic acid was further investigated in hairless mice exposed to UV‐B, in which it attenuated UV‐B‐triggered skin wrinkle formation and epidermal thickening. Topical application of 10 μmol/l ellagic acid diminished production of pro‐inflammatory cytokines IL‐1β and IL‐6, and blocked infiltration of inflammatory macrophages in the integuments of SKH‐1 hairless mice exposed to UV‐B for 8 weeks. In addition, this compound mitigated inflammatory intracellular cell adhesion molecule‐1 expression in UV‐B‐irradiated keratinocytes and photoaged mouse epidermis. These results demonstrate that ellagic acid prevented collagen destruction and inflammatory responses caused by UV‐B. Therefore, dietary and pharmacological interventions with berries rich in ellagic acid may be promising treatment strategies interrupting skin wrinkle and inflammation associated with chronic UV exposure leading to photoageing.     

Chemical peeling with salicylic acid in polyethylene glycol vehicle suppresses skin tumour development in hairless mice

BACKGROUND: Chemical peeling with salicylic acid in polyethylene glycol (PEG) vehicle is used clinically to improve the cosmetic appearance of skin that has been damaged by exposure to the sun. It is well known that cancers of the skin such as basal cell carcinoma and squamous cell carcinoma may be induced by the sun. However, the carcinogenic potential of chemical peeling agents has not been studied. OBJECTIVES: To evaluate the effects of chemical peeling with 30% salicylic acid in PEG on skin tumour formation in treated vs. control mice. METHODS: To serve as a model of sun-damaged skin, hairless SKH/hr1 mice were irradiated with ultraviolet (UV) B for 14 weeks, with or without treatment every 2 weeks with 30% salicylic acid in PEG for a total of 18 weeks. RESULTS: Not only was the total number of tumours greatly reduced in the treated vs. the control mice, but skin tumour development was also slower in the treated vs. the control mice. At the final treatment, the fractions of T and B lymphocytes and natural killer cells from spleens of both groups of mice were comparable, and interferon-gamma production did not differ. CONCLUSIONS: Our findings suggest that chemical peeling with salicylic acid in PEG may help to prevent as well as to reduce the number of UVB-induced skin tumours.     

Effect of chemical peeling on photocarcinogenesis

Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photo‐aged skin. We assessed the photo‐chemopreventive effect of several clinically used chemical peeling agents on the ultraviolet‐irradiated skin of hairless mice. Chemical peeling was done using 35% glycolic acid dissolved in distilled water, 30% salicylic acid in ethanol, and 10% or 35% trichloroacetic acid in distilled water at the right back of ultraviolet‐irradiated hairless mice every 2 weeks for glycolic acid, salicylic acid and 10% trichloroacetic acid, and every 4 weeks for 35% trichloroacetic acid for a total of 18 weeks after the establishment of photo‐aged mice by irradiation with ultraviolet B range light three times a week for 14 weeks at a total dose of 6.66 J/cm². Tumor formation was assessed every week. Skin specimens were taken from treated and non‐treated area for evaluation under microscopy, evaluation of p53 expression and mRNA expression of cyclooxygenase‐2. Serum level of prostaglandin E₂ was also evaluated. All types of chemical peeling reduced tumor formation in treated mice, mostly in the treated area but also in the non‐treated area. Peeling suppressed retention of p53‐positive abnormal cells and reduced mRNA expression of cyclooxygenase‐2 in treated skin. Further, serum prostaglandin E₂ level was decreased in chemical peeling treated mice. These results indicate that chemical peeling with glycolic acid, salicylic acid and trichloroacetic acid could serve tumor prevention by removing photo‐damaged cells.     

A short-term screening protocol, using fibrillin-1 as a reporter molecule, for photoaging repair agents

Photoaged skin is characterized by coarse and fine wrinkles. The mechanisms of wrinkle formation are undetermined, but appear to be due to changes within the matrix of the dermis and at the dermal-epidermal junction. Previous studies have identified marked reductions in procollagens I and III, collagen VII, and the fibrillin-rich microfibrillar apparatus in this area. Topically applied all-trans retinoic acid can repair photoaged dermal matrix, but this takes at least 6 mo of treatment. In this study, we have examined the abundance and distribution of fibrillin-1 prior to, and following, 192 wk of all-trans retinoic acid treatment. We have further developed a short-term protocol to determine the utility of potential repair agents, using fibrillin-1 as the marker for outcome. Individuals with clinically assessed severe photoaging were recruited to the study (n = 8). 0.025% all-trans retinoic acid, 5% sodium lauryl sulfate (irritant control), or vehicle were applied under occlusion to photoaged extensor forearm. A fourth control area was also occluded. After 96 h, punch biopsies were taken under local anesthesia and processed for either transmission electron microscopy or snap frozen. Frozen sections were prepared for immunohistochemistry and in situ hybridization immunohistochemistry. Electron microscopy revealed aberrant elastic fibers in the papillary dermis of photoaged forearm skin, with sparse microfibrillar apparatus and interstitial collagen. After application of 0.025% all-trans retinoic acid, there was increased deposition of both these dermal matrix components, with the aberrant elastic fibers no longer apparent. Significant increases (p < 0.05) were observed at the protein and mRNA levels for fibrillin-1 following all-trans retinoic acid and sodium lauryl sulfate treatments, with all-trans retinoic acid having a significantly greater effect than irritant control (p < 0.001); however, neither application had significant effect on the abundance of collagen VII or its mRNA. Investigation of collagen I synthesis revealed no difference following treatments. To ascertain the clinical relevance of using fibrillin-1 as a marker for photoaging, facial skin was biopsied at baseline and after long-term (192 wk) topical all-trans retinoic acid treatment (n = 5). Biopsies were wax-embedded and sections prepared for immunohistochemistry for fibrillin-1. Significant increases in the abundance of the microfibrillar apparatus was observed proximal to the dermal- epidermal junction (p < 0.001) following long-term all-trans retinoic acid application. This study indicates that all-trans retinoic acid can significantly affect fibrillin-1 content in photoaged skin. Furthermore, fibrillin-1 can be used as a "reporter" molecule in short-term protocols for testing the utility of topical agents in the repair of photoaged skin.     

Adipose-derived stem cells as a new therapeutic modality for ageing skin

Stem cells are undifferentiated cells, which have the important properties of self-renewal and differentiation. Adipose-derived stem cells (ADSC) have relative advantages in accessibility and abundance compared to other kinds of stem cells. Regeneration therapy using ADSC has received attention in the treatment of various dermatologic diseases. In previous studies, ADSC were shown to have antioxidant, whitening and wound-healing effects in the skin through secretion of growth factors and by activating fibroblasts. In this study, we investigated whether ADSC could be used as an anti-ageing therapy, especially by dermal collagen synthesis and angiogenesis. Subcutaneous injection of ADSC significantly increased collagen synthesis in hairless mice, and dermal thickness, collagen density and fibroblast number also increased. In addition, procollagen type I protein and mRNA expression increased, which accounts for the increased dermal collagen density. Angiogenesis, which was visualized by CD31 and NG2 immunofluorescence stains, also increased in ADSC-treated skin. Our results suggest that ADSC therapy may be useful in ageing skin. Its effects are mainly mediated by stimulating collagen synthesis in dermal fibroblasts and increasing angiogenesis.     

Enhanced proliferation and collagen synthesis of human dermal fibroblasts in chronically photodamaged skin

Cutaneous aging can be divided into intrinsic aging and photoaging. We investigated the influence of aging and photoaging on the proliferation and collagen synthesis of human dermal fibroblasts cultured 3-dimensionally in a collagen gel. We examined 11 human dermal fibroblast cell lines cultured from 3 newborn skins (1 day old), and both exposed and unexposed skin from 4 elderly volunteers (60, 60, 73, 76 years old), respectively. Newborn fibroblasts actively proliferated within the attached collagen gels compared with the elderly cell lines. Within the attached collagen gels in the presence of 10% fetal calf serum (FCS), the fibroblasts from exposed skin proliferated rapidly compared with fibroblasts from unexposed skin from the same individuals. In collagen gel and monolayer cultures with 1% FCS, the percentage of collagen synthesized by photoaged and aged fibroblasts decreased significantly compared with that by newborn fibroblasts. When the fibroblasts were cultured three dimensionally in attached collagen gels in the presence of 1% FCS, the relative levels of collagen synthesis by cultured fibroblasts from photoaged skin were increased significantly compared with those of aged skin fibroblasts from the same individuals. These results suggest that fibroblasts of exposed skin may be more active than those of unexposed skin and that the three-dimensional culture of fibroblast can be used as a model to investigate the influence of aging and photoaging on cell functions.     

Collagen loss in photoaged human skin is overestimated by histochemistry

It is well known that photoaged skin is characterized by increases in dermal matrix components that include glycosaminoglycans, proteoglycans and masses of abnormal elastic fibers accompanied by substantial collagen loss. Histochemical staining of such tissue gives the impression of "massive" loss of collagen and its replacement by these other matrix components. Early biochemical studies have lent support to this notion with a reported decrease in total collagen of approximately 45% compared to protected skin. More recent studies report considerably less, but varying, amounts of collagen loss. Rarely have the two approaches, histochemistry and biochemical analysis, been used in the same study to examine the same tissue. In this study, collagen loss was quantified biochemically in paired biopsies from sun-protected and sun-exposed arm skin of moderately photoaged female subjects (age 51-77 years). The values obtained were compared with histochemical and immunochemical findings. Quantitatively, collagen loss on a per mg protein basis was small compared to the histochemical appearance.     

Different effects of topically applied 5-fluorouracil on hairy and hairless mice

The effects of topically applied 5-fluorouracil (5-FU) ointment on hairy and hairless mice have been studied. Five per cent 5-FU ointment was applied once daily to the dorsal surface of the mice, totalling one, two or seven applications. No changes have occurred in all the hairy mice, while remarkable changes such as erosion or ulcer, followed by skin hypertrophy and pigmentation have occurred after the applications of the drug to hairless mice. In the altered hairless mice, acanthosis, the appearance of active (DOPA positive) melanocytes in the epidermis and dermal cyst wall, and moderate increase in the dermal melanocytes were seen in the marked pigmentation area. Pseudocarcinomatous hyperplasia and a high increase in the dermal melanocytes were seen in the hypertrophic skin. It is suggested that different from the hairy mice skin the hairless mice skin shows abnormal reaction to 5-FU (erosion or ulcer), resulting in epidermal hyperplasia and pigmentation.     

强脉冲光照射对小鼠皮肤胶原纤维、弹性纤维及透明质酸含量的影响

目的 探讨强脉冲光照射对昆明小鼠皮肤胶原纤维、弹性纤维、透明质酸含量的意义。方法用强脉冲光照射小鼠右侧背部皮肤,左侧为对照,取各时间点照射组和对照组皮肤进行组织学观察,包括HE染色、Ⅰ型和Ⅲ型胶原纤维饱和苦味酸-天狼猩红染色、弹性纤维Gomori醛品红法染色,同时提取皮肤组织,碱水解-分光光度法测定羟脯氨酸含量,放射免疫法测定透明质酸含量。结果 照射后2周,真皮厚度较对照组增加（t = 4.623,P < 0.05）,4周时达最大值,较对照组增加18.71%,8周时仍大于对照组,差异有统计学意义（t = 3.904,P < 0.05）。照射后1周,Ⅲ型胶原纤维较对照组增加40.54%（t = 5.129,P < 0.05）,照射后2周和4周,Ⅰ型和Ⅲ型胶原纤维均较对照组增多明显,至8周时,均大于对照组（P < 0.05）。照射后2 ~ 8周,弹性纤维均较对照组增多（P < 0.05）;照射后1 ~ 8周,羟脯氨酸含量均较对照组增多（P < 0.05）。照射后1 d和3 d,透明质酸含量显著增加,1 ~ 8周,渐进性降低,但均高于对照组（P < 0.05）。结论 强脉冲光照射小鼠皮肤可刺激真皮胶原纤维、弹性纤维、透明质酸含量增加。     

Proteolytic digest derived from bovine Ligamentum Nuchae stimulates deposition of new elastin-enriched matrix in cultures and transplants of human dermal fibroblasts

BACKGROUND: Diverse topical products and injectable fillers used for correcting facial wrinkles induce rather short-lived effects because they target replacement of dermal collagen and hyaluronan, matrix components of limited biologic durability. OBJECTIVE: Present studies were aimed at stimulation of fully differentiated human dermal fibroblasts to resume deposition of new extracellular matrix rich of elastin, the most durable and metabolically inert component of dermal ECM. METHODS: We have created a novel proteolytic digest of bovine ligamentum nuchae (ProK-60), and tested its potential biological effect on dermal fibroblasts derived from females of different ages. Northern blots, quantitative immunohistochemistry and metabolic assays were used to assess effects of ProK-60 on proliferation and matrix production in primary cultures of dermal fibroblasts, in cultures of skin explants and after implantation of stimulated fibroblasts into the skin of athymic nude mice. RESULTS: ProK-60 increased proliferation (25-30%) of cultured dermal fibroblasts and significantly enhanced their production of new elastic fibers (>250%) and collagen fibers (100%). These effects were mostly mediated by stimulation of cellular elastin receptor. In contrast, ProK-60 inhibited production of fibronectin (-30%) and chondroitin sulfate proteoglycans (-50%). ProK-60 also activated proliferation of dermal fibroblasts, mostly derived from the stratum basale and induced deposition of elastic fibers in cultures of skin explants. Moreover, human fibroblasts pre-treated with ProK-60 produced abundant elastic fibers after their injection into the skin of athymic nude mice. CONCLUSION: The described biological effects of ProK-60, including its unique elastogenic property, encourage use of this compound in cosmetic formulations stimulating rejuvenation of aged skin.     

Remodeling of the human dermis after application of salicylate silanol

Recently, a controlled double-blind study in patients with photo-aged facial skin demonstrated the beneficial role of oral intake of silanol for skin, hair and nails. The aim of our pilot study was to investigate histologic alterations in human skin after injection of silanol. Seven healthy female caucasian volunteers with a moderate degree of photoaged skin received ten sessions of weekly injections of 0.1% salicylate silanol in the left ventral lateral forearm. The histologic features of punch biopsies of the treated area and the nontreated contralateral arm were compared and the collagen and elastic fibers quantified. Texture analysis was performed on digitalized microscopic images by analyzing the Sarkar fractal dimension or amplitudes (inertia values) after Fast Fourier transformation. The treated area revealed a statistically significant increase of the density of both collagen and elastic fibers. Texture analysis showed more compact and homogenously distributed collagen fibers after silicon injection. Our results suggest that the application of silicon may stimulate the production of collagen and elastic fibers leading to remodeling of the dermal fiber architecture, which may explain the improvement of the skin surface observed in clinical studies.     

Effect of chemical peeling on the skin in relation to UV irradiation

Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photoaged skin. However, it needs to be clarified whether the repetitive procedure of chemical peeling on photodamaged skin is safe and whether the different chemicals used for peeling results in similar outcomes or not. In this article, we reviewed the effect of peeling or peeling agents on the skin in relation to ultraviolet (UV) radiation. The pretreatment of peeling agents usually enhance UV sensitivity by inducing increased sunburn cell formation, lowering minimum erythematous dose and increasing cyclobutane pyrimidine dimers. However, this sensitivity is reversible and recovers to normal after 1-week discontinuation. Using animals, the chronic effect of peeling and peeling agents was shown to prevent photocarcinogenesis. There is also an in vitro study using culture cells to know the detailed mechanisms of peeling agents, especially on cell proliferation and apoptotic changes via activating signalling cascades and oxidative stress. It is important to understand the effect of peeling agents on photoaged skin and to know how to deal with UV irradiation during the application of peeling agents and treatment of chemical peeling in daily life.     

P-cadherin expression in skin peeled with phenol or trichloroacetic acid (TCA)

P-cadherin expression patterns were studied in trichloroacetic acid (TCA) or phenol treated skin. The expression was absent or very weak on the basal cell surfaces by day 2. Seven days after peeling, P-cadherin was clearly distributed in a continuous granular pattern over the cell surface of the entire epidermis of the 40% TCA treated skin, in a weak granular pattern on a few suprabasal cells and basal cells of the phenol treated skin, and very weakly expressed on the lateral surfaces and in the cytoplasm of basal cells of the 60% TCA treated skin. Based on the present results and previous reports, it is likely that there are distinct patterns of P cadherin expression. Furthermore, a specific type of P cadherin expression might be involved in wound healing in general, which could provide new insights into tissue repair mechanisms after chemical peeling.     

The hairless mouse as a model for study of local and systemic atrophogenic effects following topical application of corticosteroids.

The hairless mouse has been used as a model to distinguish between local and systemic atrophogenic effects of topical steroids. Hydrocortisone-17-butyrate, betamethasone-17-valerate, budesonide and clobetasol-17-propionate were applied topically daily for 21 days. Skinfold thickness and dermal DNA synthesis of treated and untreated skin were evaluated as parameters of local and systemic atrophogenicity. Further, body weight gain and thymus weight were assessed as markers of systemic activity. With respect to local effects, skin thickness and dermal DNA synthesis both proved to be good parameters. Of the systemic parameters, thymic involution and body weight gain paralleled quite well the skin thinning on the untreated side. The results confirmed the potency differences of the steroids. Furthermore, they emphasize the usefulness of the hairless mouse to assess the relative safety with respect to local and systemic side effects of chronically applied topical corticosteroids.