Protection from physical noxae.

Protection from physical noxae must include multiple approaches; physical irritant contact dermatitis develops most likely when the cumulative exposure to several physical factors, such as climatic environmental conditions and friction, pressure or occlusion is given. The additive effect of these conditions, frequently found in modern working environments, not only provokes barrier disturbances, but also inflammatory reactions of the deeper layers of the skin. This review reflects on some examples of occupational physical irritant contact dermatitis (PICD) and the current understanding of its possible pathomechanism. On the one hand, the literature reveals epidemiological studies and case reports and on the other hand murine studies. The combination of both views may permit new insights into the pathogenic mechanisms of PICD and its prevention.

The pH of commercially available rinse-off products in Sri Lanka and their effect on skin pH.

INTRODUCTION: Initially linked to antimicrobial function, the acidic skin pH plays a key role in permeability barrier homeostasis and integrity of the stratum corneum. Barrier recovery is delayed when acutely perturbed skin sites are exposed to a neutral pH. OBJECTIVE: To evaluate the pH of commercially available rinse-off products in Sri Lanka, and the effect of detergent rinses on skin pH and its recovery rate. METHODS: The pH of 18 rinse-off products was determined using pH indicator paper and a pH meter. The effect of an alkaline (pH 9) and an acid (pH 5.5) rinse-off product on the hand skin pH was compared in 48 healthy volunteers after single and multiple applications. The skin pH of the dorsum of hands was measured in nurses before (n = 131) and during (n = 40) a duty shift that involved frequent hand washing using alkaline soap. RESULTS: Soaps available in Sri Lanka have a pH of 9.1-10.5. The pH of syndets and cleansers range from 5.5-7.0. Five minutes after hand washing, the mean skin pH increased by 1.7 +/- SD 0.5 pH units with alkaline soap, and by 0.8 +/- SD 0.4 pH units with acidic cleanser (p < 0.0001). Recovery of pH was slower when alkaline soap was used. The increase in skin pH was significantly greater when hands were repetitively washed with alkaline soap (p < 0.0001). The mean skin pH values of nurses before (4.9 +/- SD 0.4) and during (5.7 +/- SD 0.7) the work shift were significantly different (p < 0.0001). CONCLUSIONS: Alkalinisation with rinse-off products increases the skin pH with potential functional and clinical implications.

[Chemical peels]. / Chemical Peel Anweisungen für die Praxis.

Chemical peels have become established over the past 40 years as an effective outpatient method for skin rejuvenation as well as the treatment of a variety of skin conditions. Although laser skin rejuvenation has claimed much attention in recent years, phenol peels, despite problems with scarring and hypopigmentation, remains the gold standard for skin resurfacing [11], against which other methods should be evaluated [21]. We present both a theoretical overview of chemical peels and practical step-for-step instructions.

In vivo and in vitro evidence for autocrine DCoH/HNF-1alpha transcription of albumin in the human epidermis.

The presence of albumin in the human epidermis has been reported more than a decade ago, but until now, it was assumed that this protein is synthesized in the liver and transported to the avascular skin. To our knowledge, transcription of albumin in the human epidermis was never considered. In this report, we present for the first time evidence for autocrine synthesis of albumin in the human epidermis in keratinocytes in situ and in vitro. Using double immunofluorescence labelling, we identified that albumin colocalized together with its transcription factor PCD/DCoH/HNF-1alpha in suprabasal keratinocytes in human full-thickness skin sections and in keratinocytes cultured in serum-free medium. Moreover, albumin and HNF-1alpha protein expression was confirmed by Western blotting in undifferentiated and differentiated keratinocytes as well as in human epidermal suction blister roof extracts. Reverse-transcriptase polymerase chain reaction analysis from human epidermal keratinocytes and epidermal suction blister roofs revealed the transcription of albumin. Using in vivo fluorescence excitation spectroscopy at the surface of human skin, we confirmed albumin as a major constituent yielding a lambda(max) at 295 nm, which was assigned to the single tryptophan 214 fluorophore in this protein. This in vivo result is in agreement with albumin concentrations of 10(-3) M, underlining the importance of this protein in epidermal homeostasis.

[Anti-aging. Facts and visions]. / Anti-aging. Fakten und Visionen.

Youth and beauty are today considered to be social ideals. However, as these are not permanent, ever more measures are offered which are reputed to prevent aging, for example of the skin. Most of these measures do not follow scientific recommendations. Within this trend to youth and beauty, the use of the terms aging and anti-aging (rejuvenation) are more frequent. These will be discussed in the present manuscript along with the facts and visions of some well known "anti-aging measures".

Implementation of fatty acid carriers to skin irritation and the epidermal barrier.

Acute perturbations are followed by barrier repair and enhanced lipid synthesis, as well as cellular fatty acid trafficking, yet irritation of the skin may be induced by repeat disturbance of barrier function. Recently, new insights in cellular fatty acid transport and metabolism have evolved with respect to skin irritation and barrier disturbances: (1) Employing sodium dodecyl sulfate, skin irritation is accompanied by the induction of an epidermal (E) cytosolic fatty acid binding protein (FABP) associated with enhanced barrier repair. Whether E-FABP contributes to the water barrier function in normal skin remains to be elucidated; (2) Cutaneous inflammation, as it occurs in irritant contact dermatitis, can be reduced by peroxisome proliferating activated receptor (PPAR) agonists, such as linoleic acid, with clinical effects comparable to that of glucocorticoids; (3) PPARalpha agonists accelerate barrier recovery and enhance lamellar body synthesis, neutral lipid synthesis, in particular that of ceramides and cholesterol; (4) PPARalpha agonists increase the minimal erythema dose in UVB-irradiated human skin. This review provides a brief overview of the current understanding of mammalian fatty acid (FA) metabolism with respect to epidermal barrier abrogation and repair, including new insights into cellular FA transport and metabolism.

Fatty acid uptake by cultured human keratinocytes grown in medium deficient in or supplemented with essential fatty acids.

Epidermal linoleic acid, i.e. essential fatty acid (EFA), is essential for cutaneous barrier function. Cultured human keratinocytes, routinely used for studies of lipid metabolism, are grown in a keratinocyte serum-free medium (KSFM), under conditions that reveal EFA-deficient cells. Here, fatty acid (FA) uptake was analysed in human adult keratinocytes grown either under EFA-deficient conditions [KSFM supplemented with 10% FCS (A) or 1% UltroserG (B)] or EFA-supplemented conditions [KSFM supplemented with a devised FA cocktail (C) or evening primrose oil (D)]. The FA composition of the total cellular lipid and major lipid fractions was analysed by gas chromatography. Cells grown with supplements A or B balanced their EFA-deficient state primarily with oleic acid. Cells grown with supplements C or D normalized to the epidermal FA composition in vivo with raised linoleic and lower oleic acid contents. When cells were grown longer than 48 h with supplements C or D decreased cell growth was observed. FA uptake was curvilinear with preference for linoleic over oleic acid under all culture conditions. The uptake of linoleic acid by cells cultured with supplement B was twice the uptake of those cultured with supplement A, while the uptake of oleic acid was similar under both culture conditions. Oleic acid uptake of cells cultured with supplement C or D was lower. These results show that the uptake of linoleic, but not that of oleic acid, is influenced by the extracellular FA composition, and that EFA-supplemented keratinocytes compared to EFA-deficient cells might serve as an in vitro model for the study of EFA metabolism.

Ferrochelatase activities in patients with erythropoietic protoporphyria and their families.

Ferrochelatase, estimated as zinc chelatase, was measured in the lymphocytes of 30 patients with erythropoietic protoporphyria (EPP), in 35 first- or second-degree relatives of patients with EPP, and in 50 healthy controls. In 30 EPP patients the zinc chelatase level (mean +/- standard deviation, SD) was 0.45 +/- 0.10 nmol of zinc protoporphyrin per hour per milligram of protein, in 14 EPP carriers the zinc chelatase level (mean +/- SD) was 0.42 +/- 0.09 and in 50 healthy controls the zinc chelatase level (mean +/- SD) was 0.84 +/- 0.27. All patients with EPP were also demonstrated to have an elevated protoporphyrin level in their red blood cells: the erythrocyte protoporphyrin levels were as follows EPP patients (mean +/- SD) 1300 +/- 758 nmol protoporphyrin/dl, EPP carriers (mean +/- SD) 60 +/- 24, and healthy controls (mean +/- SD) 50 +/- 25 (P < 0.001 for EPP patients compared to controls and EPP carriers). The families of 12 out of 15 EPP patients were examined with respect to the mode of inheritance of the disorder. Of 35 relatives, 14 were carriers of EPP, as characterized by reduced zinc chelatase activity in lymphocytes and by a normal protoporphyrin level in red blood cells. None of the 14 EPP carriers had presented with clinical symptoms of EPP. The mod of inheritance was autosomal dominant in seven of the 12 examined families, and autosomal recessive in two. In two families only one parent could be investigated, but we nevertheless concluded that the inheritance was autosomal dominant. Inheritance in one EPP family could not be elucidated as both parents showed normal zinc chelatase levels and did not demonstrate abnormal erythrocyte protoporphyrin levels.

Palmoplantar keratoderma with an unusual composition of stratum corneum and serum sterol derivatives: a new entity?

Little is known about the aetiology and pathogenesis of the different types of inherited and acquired palmoplantar keratodermas. We describe a condition of painful palmoplantar keratoderma with an altered stratum corneum lipid pattern which may be responsible for the excessive cornification. Plantar stratum corneum lipids were analysed by quantitative thin-layer chromatography. Serum lipids, and the activities and gene loci of the enzymes serum steroid sulphatase and arylsulphatase C were also determined. Examination revealed that both the stratum corneum and the serum cholesterol sulphate (CS) content were significantly elevated in comparison with the stratum corneum cholesterol ester content. The cholesterol content was unchanged compared with controls. Serum activities of steroid sulphatase and arylsulphatase C were decreased, but not to the extent found in recessive X-linked ichthyosis. Their gene loci did not show any deletions. This unique distribution of stratum corneum sterol derivatives, reflected by the elevated serum CS concentration, may contribute to the altered structural and functional properties of intercellular lipid lamellae within the stratum corneum of this type of keratoderma.

Porphyrin concentrations in various human tissues.

We measured the concentrations of total porphyrins and their metabolites (uro-, hepta-, hexa-, penta-, copro- and protoporphyrin) in various human tissues: liver, erythrocytes, skin, adipose tissue, and mammary gland. The porphyrin concentrations varied within major limits, e.g., 3.1 +/- 2.3 nmol porphyrins/g liver and 0.50 +/- 0.10 nmol/g erythrocytes. No significant differences were detectable in other tissues in comparison with liver. In all tissues, the predominant metabolite was protoporphyrin, followed by coproporphyrin, whereas only low concentrations of higher carboxylated porphyrins such as uroporphyrin were detectable. It is concluded that porphyrin metabolism and its regulation is similar in all human tissues, perhaps with some small differences in the erythrocytes.

Quantitative screening of human stratum corneum lipids by sequential one-dimensional thin layer chromatography.

There is a need in many studies on the epidermal permeability barrier for practical and reliable separation of all major fractions of human stratum corneum lipids. Various methods have been described including thin layer chromatography, high performance thin layer chromatography and iatroscan. However, none of these methods seems to be applicable for an inexpensive, rapid and reliable analysis of a large number of samples. Here, such a method for the separation and quantification of all major stratum corneum lipid fractions is presented. This method employs the one-dimensional separation of stratum corneum lipids using thin layer chromatography. The systems used herein are based upon various modifications of the solvents, solvent ratio and developing distance of each system. For quantification of chromatographed and charred lipids a Desaga densitometer is used. The system described here had been successfully applied to 550 samples of human stratum corneum lipids.

Evidence for a novel keratinocyte fatty acid uptake mechanism with preference for linoleic acid: comparison of oleic and linoleic acid uptake by cultured human keratinocytes, fibroblasts and a human hepatoma cell line.

Keratinocytes require the essential fatty acid (FA), linoleic acid (LA), for the synthesis of stratum corneum membrane lipids. A plasma membrane-FA binding protein (PM-FABP), is postulated to mediate cellular FA-uptake in hepatocytes and several other tissues, but the mechanism whereby exogenous FA are taken up by keratinocytes has not been investigated. This study examines the uptake of LA and oleic acid (non-essential) in cultured human keratinocytes, in comparison to dermal fibroblasts and the human hepatoma cell line, HepG2. As previously reported for hepatocytes, FA-uptake in keratinocytes was curvilinear, with an initial (30 s) rapid cellular influx. The initial uptake component was temperature dependent, exhibited saturable kinetics and was significantly inhibited by pretreatment with trypsin. In contrast, fibroblast FA-uptake lacked an initial rapid uptake component, was relatively temperature insensitive, and was not inhibited by trypsin. Keratinocytes differed from both hepatocytes and fibroblasts by more rapid uptake of LA in comparison to oleic acid during the initial influx phase. Moreover, FA-uptake in keratinocytes was not inhibited by preincubation with a anti-rat liver PM-FABP antibody. These data provide evidence for a PM-FA transporter in keratinocytes that is distinct from the hepatic PM-FABP. The apparent preference of the putative keratinocyte FA transporter for LA may function to ensure epidermal capture of sufficient LA for barrier lipid synthesis.

High-affinity fatty acid-binding activity in epidermis and cultured keratinocytes is attributable to high-molecular-weight and not low-molecular-weight fatty acid-binding proteins.

Fatty acid-binding proteins (FABPs) are abundant low-molecular-weight cytosolic proteins in tissues involved in fatty acid (FA) metabolism. Because epidermis is also an active lipogenic tissue, we examined cytosols from murine and porcine epidermis and cultured human keratinocytes and fibroblasts for FABPs. High-affinity FA-binding activity was present in both epidermis and differentiated keratinocytes, whereas no high-affinity FA-binding activity was found in cultured human fibroblasts or undifferentiated keratinocytes. By column chromatography, a single binding peak was identified in the high (90-100 kDa)-molecular-weight range and no binding activity was evident in the low (14-15 kDa)-molecular-weight range, where conventional FABPs elute. Moreover, rabbit anti-rat heart FABP, anti-rat intestine FABP, and anti-rat liver FABP antisera did not identify proteins in the 14-15-kDa range in murine epidermal cytosol by Western immunoblots, whereas the anti-rat-heart antibody recognized a protein of approximately 32 kDa. Isoelectric focusing of differentiated keratinocyte cytosol demonstrated a single FA-binding peak having a pI of approximately 4.0. Analysis of this binding peak by SDS-PAGE revealed peptides of approximately 66 and 38 kDa. These findings suggest the possibility that the FA-binding protein in keratinocyte cytosol normally exists as a heterodimer. Western immunoblots of both differentiated keratinocyte cytosol and keratinocyte-conditional media stained with a rabbit anti-human serum albumin antibody identified a protein of approximately 67 kDa, but the electrofocused fraction did not react with this antibody. Thus, epidermis and differentiated keratinocytes possess high-affinity cytosolic FA-binding activity that cannot be ascribed either to conventional low-molecular-weight FABPs or to albumin.

Photosensitivity induced by quinidine sulfate: experimental reproduction of skin lesions.

A case of quinidine sulfate-induced photodermatitis is reported. The photosensitive reaction to quinidine sulfate was reproducible in the photopatch test and after oral intake plus ultraviolet A (UVA) irradiation. Eczematous dermatitis was provoked after intradermal injection of in vitro UVA-irradiated quinidine sulfate only in the presence of patient's serum. The clinical picture and histology suggest an allergic reaction. The photobinding of quinidine sulfate to a potential carrier protein in skin or serum seems to be of crucial importance for this type of photodermatitis. Quinidine sulfate is frequently used as an antiarrhythmic drug. Its potential as a photosensitizer should always be considered.