Effect of high‐fat meal intake on the pharmacokinetic profile of ivermectin in Japanese patients with scabies

Ivermectin (IVM) is used as an anthelmintic agent in many countries. To evaluate the effect of high‐fat (HF) meal intake on the pharmacokinetics of IVM, a clinical trial was conducted in Japanese patients with scabies. The patients were administrated Stromectol^® tablets in the fasted state, and after 1 week they were also administrated it after a HF meal (fed state). After the administration, IVM concentrations in plasma and the stratum corneum were determined. The geometric mean of fed/fasted ratio of area under IVM concentration‐time curve (AUC) in plasma was 1.25 (90% confidence interval, 1.09–1.43), suggesting the tendency to increased absorption after a HF meal. The fed/fasted ratio of the maximum IVM concentration in the stratum corneum was well correlated with that in plasma. In addition, no serious adverse events were observed during the trial, while a mild increase of aspartate aminotransferase and alanine aminotransferase activity in plasma was observed under the fed state in two patients. The mean AUC of IVM in plasma of those two patients were approximately threefold higher than that of the other patients at that time. On the other hand, the treatment success rate was 76.9% at 7 days after the second administration, which was comparable with the expected level. The present study not only demonstrates that HF meal intake increases the IVM concentration in plasma and the stratum corneum in Japanese patients with scabies, but also suggests the possibility that HF meals increase the risk of hepatic dysfunction by the increased exposure of IVM.     

Effect of regular sauna on epidermal barrier function and stratum corneum water-holding capacity in vivo in humans: a controlled study

During the last few years, sauna has become the epitome of wellness. Besides studies in general medicine evaluating the health benefit of sauna, e.g. on the cardiovascular system, no systematic study regarding skin physiology has been published. The present exploratory study was intended to analyse the effect of regular Finnish sauna on skin physiology. The effect of regular sauna bathing was assessed with non-invasive instruments: stratum corneum water-holding capacity, skin redness, transepidermal water loss and surface skin pH were analysed in 41 healthy volunteers, aged 20-49 years, in a group with regular sauna exposure compared to a control group with no regular sauna exposure. A more stable epidermal barrier function, an increase in stratum corneum hydration, a faster recovery of both elevated water loss and skin pH after exposure to 2 x 15 min sauna at 80 degrees C could be demonstrated in volunteers with regular sauna. Heart beat rate and ionic concentration in sweat as well as epidermal blood perfusion showed a training effect under regular sauna. A decrease in casual skin sebum content on the skin surface of the forehead was observed in these volunteers. The present data suggest a protective effect of regular sauna on skin physiology, especially surface pH and stratum corneum water-holding capacity.     

Protein oxidation in human stratum corneum: susceptibility of keratins to oxidation in vitro and presence of a keratin oxidation gradient in vivo.

The stratum corneum is located at the interface between body and environment and thus is constantly exposed to a pro-oxidative environment. Previously, we have demonstrated that stratum corneum lipids are targets of oxidative stress induced by ozone and by ultraviolet A and B exposure. Here, we employed an immunoblotting technique to detect protein oxidation in human stratum corneum obtained by tape stripping. After lysis, protein carbonyl groups were measured by derivatization with dinitrophenylhydrazine, separation by sodium dodecylsulfate-polyacrylamide gel electrophoresis, and immunoblotting using antibodies against dinitrophenyl groups. Keratin 10, identified by use of specific antibodies and by microsequencing, was demonstrated in vitro to be oxidizable by ultraviolet A irradiation, hypochlorite, and benzoyl peroxide. In vivo, a keratin 10 oxidation gradient with low levels in the lower stratum corneum layers, and about 3-fold higher contents of carbonyl groups towards the outer layers was demonstrated in forehead stratum corneum of healthy volunteers (n = 6). As protein oxidation can be associated with an increased susceptibility to proteases, this finding may be important for better understanding the process of desquamation.     

Biophysical changes after mechanical injury of the stratum corneum in normal skin

Scrubbing off the stratum corneum with a rough towel after soaking in warm water is a bathing custom unique to Korea. However, Korean dermatologists have advised against this practice due to the potential harm that it may cause, though there is little data to support this advice. This study aimed to evaluate the changes in biophysical characteristics after such mechanical injury of stratum corneum, as reflected by water-holding capacity, stratum corneum barrier function, and stratum corneum turnover time (SCTT). 10 Korean female volunteers (aged 19-34 years) were enrolled in this study to investigate the acute effects and 32 volunteers (aged 19-49 years) the chronic effects. After soaking in warm water (36 degrees C) for 5 min, the flexor surfaces of the forearms were scrubbed with a rough towel. The volunteers' forearms were divided into 4 compartments, and each compartment was scrubbed 0, 5, 10, and 15x, respectively. After a single injury of the stratum corneum, there was an initial decrease in water-holding capacity until 6 h. Thereafter, it increased until day (D) 3, when it began to descend to the normal range. The transepidermal water loss (TEWL) values also peaked at D2 and declined thereafter. However, there were no changes in either water-holding capacity or skin barrier function, and only the SCTT was significantly shortened, after chronic injury of the stratum corneum.     

空气污染对皮肤角质层蛋白羰基化水平的影响及粉红胡椒木提取物和脂质混合物对皮肤损伤的防护作用

目的 研究空气污染对皮肤角质层蛋白羰基化水平的影响,评估粉红胡椒木提取物和脂质混合物对皮肤损伤的防护作用。方法 预实验分析影响因素后,荧光标记法检测34例健康受试者不同部位皮肤角质层蛋白羰基化水平。利用定制的污染模拟箱,以香烟烟雾模拟污染物, 将15名健康受试者前臂屈侧向上暴露于污染模拟箱中,分别于暴露后0、1、2、4、5 h用D?squame胶片采集角质层样本。选14例健康受试者,在单侧前臂屈侧选择相邻的3个区域分别外用1%粉红胡椒木提取物的水溶液（胡椒木组）、去离子水（对照组）或不涂任何样品（空白组）,然后将手臂在污染模拟箱中暴露5 h,暴露前后采集各区域角质层样本。另选16例健康受试者,在单侧前臂屈侧选取3处区域分别外用含5% 脂质混合物的乳液（脂质混合物组）、不含脂质混合物的安慰剂乳液（对照组）或不涂任何样品（空白组）,然后将手臂在污染模拟箱中暴露5 h,暴露前后采集各区域角质层样本。纳入20例健康受试者进行双盲半脸临床测试,即随机选择半脸外用含1%粉红胡椒木提取物的乳液,另外半脸外用安慰剂乳液,于产品使用前和使用56 d后,采用D?Squame胶片在受试者的面颊部分别采集角质层样本。采用荧光标记法检测上述角质层样本中皮肤蛋白羰基化水平。结果 对34名受试者检测显示,人体不同部位蛋白羰基化水平（平均荧光强度）存在显著差异（P < 0.001）,其中,面颊（26.3 ± 7.1）和额部（22.9 ± 7.9）显著高于手臂（14.7 ± 4.9）和腰背部（12.6 ± 4.2）（均P < 0.001）,且手臂蛋白羰基化水平显著高于腰背部（P = 0.046）。短期模拟加速暴露实验中,蛋白羰基化水平随污染暴露时间的增加而持续升高（R2 = 0.995 9）,暴露5 h后,胡椒木组和脂质混合物组皮肤角质层蛋白羰基化水平升高值分别为9.7 ± 5.2和5.8 ± 4.9,低于各自的空白组（19.0 ± 10.0、17.4 ± 8.8,均P < 0.005）和对照组（18.5 ± 7.3、15.9 ± 6.4,均P < 0.005）,差异均有统计学意义。长期人体测试中,20名受试者使用含1%粉红胡椒木提取物的乳液8周后,与安慰剂侧相比,面部蛋白羰基化水平显著降低。结论 空气污染加剧皮肤角质层蛋白羰基化损伤,粉红胡椒木提取物和脂质混合物能有效降低蛋白羰基化水平。     

Large scale study of epidermal recovery after stratum corneum removal: dynamics of genomic response

Please cite this paper as: Large scale study of epidermal recovery after stratum corneum removal: dynamics of genomic response. Experimental Dermatology 2010; 19: 259–268. Abstract: The stratum corneum (SC) is a superficial skin compartment that protects the body from the outside environment. Any disturbance of this function induces cascading steps of molecular and cellular repair in the whole epidermis. The aim of this study was to investigate epidermal gene expression following SC removal by tape stripping. Twenty‐nine healthy male volunteers were included (27 ± 4 years old). Tape stripping was processed on one inner forearm, the other unstripped forearm served as a control. Epidermis samples were collected at 2, 6, 19, 30 and 72 h after tape stripping. Trans‐epidermal water loss measurements were performed at each step to monitor barrier restoration. Total RNA was extracted from collected epidermis samples and analysed by using DermArray® cDNA microarrays. Among 4000 genes under investigation, we found that the expression of 370 genes varied significantly at least once during the time following stripping. Using an original clustering method, the modulated genes were gathered into eight groups. A functional characterization of the clusters enabled us to get a dynamic and global view of the main molecular processes taking place during epidermal recovery.     

Effects of ultraviolet A and B on the skin barrier: a functional, electron microscopic and lipid biochemical study.

To investigate the effects of ultraviolet A (UVA) and B (UVB) on the skin barrier, functional, electron microscopic and lipid biochemical studies were performed on normal and UV-irradiated skin of volunteers. Skin reactivity against primary irritants was evaluated using the alkali resistance test, the dimethylsulfoxide test and the sodium lauryl sulfate test. In all 3 irritation models, UVA- and UVB-irradiated areas were more resistant to damage than normal skin, indicating improvement of the barrier function after UV irradiation. In a second series of experiments, biopsies were taken and processed for electron microscopic evaluation of the stratum corneum. UVB significantly increased the horny cell layers; UVA did not alter the thickness of the stratum corneum. Finally, stratum corneum lipids were extracted in vivo and quantified after high-performance thin-layer chromatography. UVB and, to some extent, UVA exposure increased the amount of all stratum corneum lipids. This was also observed in all major ceramide subfractions.     

The Azerbaijani scrub: a simple method to harvest large amounts of stratum corneum

BACKGROUND: The study of skin barrier constituents may require collection of much stratum corneum. Existing methods are inadequate and/or difficult. METHODS: A simple and safe method to harvest stratum corneum from glabrous human skin derives from the bathing practices of people in Azerbaijan. The method requires water immersion of the subject for 30 min immediately followed by vigorous scrubbing of skin with a moist rough crepe mitten. RESULTS: This scrubbing method causes the separation of large amounts of stratum corneum which is easily harvested. CONCLUSION: The method facilitates study of stratum corneum components, including intercellular lipids.     

New non‐invasive method for evaluation of the stratum corneum structure in diseases with abnormal keratinization by immunofluorescence microscopy of desmoglein 1 distribution in tape‐stripped samples

The corneodesmosomes in the stratum corneum are critical for the maintenance of stratum corneum integrity. To evaluate the normal and diseased keratinization states in the epidermis, we studied the distribution of desmoglein 1 (DSG1), a major component of corneodesmosomes, in samples of the stratum corneum obtained by tape stripping, a non‐invasive method. Samples were collected from lesional skin of four patients with psoriasis and three with lichen planus, and from non‐lesional skin of three volunteers. Upper stratum corneum cells were obtained by tape stripping and skin biopsies were obtained from adjacent sites. Tape‐stripped samples were examined by immunofluorescence microscopy using anti‐DSG1 monoclonal antibody, in combination with histopathology of skin biopsies. In normal human stratum corneum, which shows basket‐woven orthokeratosis, DSG1‐containing fluorescent dots were distributed on the lateral cell–cell contact areas of plasma membrane, but not on the dorsal/ventral plasma membrane, and formed a well‐ordered hexagonal network structure. In psoriatic stratum corneum, fluorescent dots were distributed throughout the cell membrane at ventral aspects of corneocytes as well as at the lateral cell–cell contacts. In lichen planus, fluorescent dots were distributed homogeneously and/or heterogeneously on the ventral surface in some cells. Adjacent cells lacked DSG1 at the lateral cell–cell contacts, but were instead separated by distinctive black‐gap lines. These results suggest that the intercellular adhesion by DSG1 may depend on the lateral plasma membrane in normal human stratum corneum, on the dorsal/ventral plasma membrane in lichen planus, and on both lateral and dorsal/ventral plasma membranes in psoriatic stratum corneum. Tape stripping and DSG1 immunofluorescence visualizes adhesion features of corneocytes and has considerable potential for evaluation of abnormal keratinization and the process of healing in response to treatment.     

A possible function of structural lipids in the water-holding properties of the stratum corneum

In order to clarify the possible role of lipids in the water-holding property of stratum corneum, the forearm skin of 6 healthy male volunteers was treated with acetone/ether (1/1) for 1, 5, 10, and 20 min. A prolonged treatment period of 5-20 min produced a chapped and scaly appearance of the stratum corneum without any inflammatory reactions. Under these conditions, there was a marked decrease in the water-holding capacity of the stratum corneum accompanied by a considerable and selective loss of intercellular lipids such as cholesterol, cholesterol esters, and phospholipids. These impairments persisted until day 4 after treatment. Electron microscopic observation of the altered stratum corneum revealed that naturally occurring intercellular materials were absent, leaving the area with the appearance of a vacant space. These findings suggest an additional and essential role of the specific structural lipids for the water-holding properties of the stratum corneum.     

Efficacy and tolerance of oral ivermectin in scabies

Objective The aim of this open-label study was to investigate the therapeutic effect and adverse reactions of oral ivermectin in scabies patients.
Background There is much confusion over reports of efficacy, adverse reactions and relapses after oral treatment of scabies with ivermectin.
Methods Nineteen patients, ten otherwise healthy outpatients with scabies, and nine inpatients with scabies and another skin disease (dermatomyositis, 3; pemphigus, 2; bullous pemphigoid, 1; pyoderma, 1; HIV, 1; Behcet's disease, 1) were treated with an oral dose of 0.2 mg/kg ivermectin (1% water solution) on days 1 and 8. The presence of live mites and ova in the patient's skin was investigated before, during and after the treatment.
Results None of the 19 patients with scabies had evidence of scabies after the second dose of ivermectin. In seven patients we noted the enhancement of pruritus 24–72 h after the first administration of ivermectin. In three patients the skin manifestation, vesicle-pustular rash increased between the second and the fourth day.
Conclusion The advantages of oral ivermectin treatment in scabies patients are: high therapeutic efficacy against Sarcoptes scabiei , good tolerance and influence of the drug on the whole skin surface and on clinical symptoms. The administration of the drug is easy and quick.     

Efficacy of erbium:yttrium-aluminum-garnet laser-assisted delivery of topical anesthetic

BACKGROUND: Penetration through the stratum corneum limits effectiveness of topical anesthetics. OBJECTIVE: Our aim was to evaluate the effectiveness of 5% lidocaine (ELA-Max) cream applied after erbium:yttrium-aluminum-garnet (Er:YAG) laser ablation of the stratum corneum. METHODS: Randomized, controlled, split-face comparison of anesthesia was performed on 12 volunteers. The stratum corneum was painlessly ablated with a low-fluence Er:YAG laser on half of the face, then the whole face was covered with ELA-Max cream for 60 minutes. Full-face laser resurfacing was performed, and visual analog pain scores (0 to 10) were recorded during each of 2 passes. RESULTS: Laser-assisted topical anesthesia demonstrated significantly lower mean pain scores than topical anesthesia alone. This was more pronounced during the more painful second pass. Resurfacing after laser-assisted topical anesthesia was well tolerated by 72% of subjects in pass 1 and 58% in pass 2. CONCLUSION: Laser-assisted topical anesthesia is fast, painless, and substantially more effective than conventional topical anesthesia but does not provide adequate anesthesia for full-face resurfacing in all subjects.     

Increased carbonyl protein level in the stratum corneum of inflammatory skin disorders: A non‐invasive approach

The stratum corneum (SC) is the interface of body and environment, and is continuously exposed to oxidative stress, resulting in carbonyl modification of proteins. We have developed a simple and non‐invasive method to assess carbonyl protein (CP) level in the SC, applied it to various kinds of skin, and revealed a link between the stratum corneum carbonylated protein (SCCP) level and water content in the SC. The purpose of the present study is to examine the SCCP level in inflammatory skin disorders associated with xerosis. Psoriasis vulgaris (PV) and atopic dermatitis (AD) are typical inflammatory skin disorders, of which the stratum corneum shows markedly low water content. SC samples were non‐invasively collected from the lesional and non‐lesional areas of PV and AD by adhesive tape stripping, and their carbonyl groups were determined by reaction with fluorescein‐5‐thiosemicarbazide. The average fluorescence intensity of the SC was calculated as SCCP level. Higher SCCP level was observed in the lesional area of PV as compared with non‐lesional area or healthy control. Lesional area of AD also exhibited higher SCCP level than corresponding non‐lesional area, of which SCCP level was slightly higher than the healthy control. These data suggest the involvement of oxidative modification of the SC protein, at least in part, in generation of xerotic skin in inflammatory skin disorders as well as dry skin in healthy subjects.     

In vivo quantitative analysis of the effect of hydration (immersion and Vaseline treatment) in skin layers using high‐resolution MRI and magnetisation transfer contrast*

Background/aims: Many claims are made as to the efficacy of topical preparations in moisturising the skin, yet most of these claims cannot be substantiated by scientific study for the skin layers beneath the stratum corneum, and yield no information on the remainder of the epidermis and dermis. This argues for an in vivo quantitative method for measuring the effect of water loading extended to various layers of the skin. Methods: Detailed high‐resolution in vivo MRI studies of hydration and dehydration of finger pad skin layers were conducted on one normal subject using two moisturisation methods (topical white soft paraffin (Vaseline) and water immersion). The dehydration study was carried out immediately following removal from prolonged skin moisturisation. Inter‐individual variability for skin hydration (group study) was studied in seven healthy volunteers at 0 and 7 h hydration with Vaseline. Location dependence in skin hydration was investigated on the same subject by looking into the hydration of forearm and finger pad skin. System stability and measurement reproducibility was verified through a detailed phantom study. Results: Images of normal and hydrated human skin were obtained in vivo at voxel dimensions of 50 μm×150 μm×1000 μm. The effect of hydration and dehydration as a function of exposure to moisturiser (i.e. water and Vaseline) on the image signal intensity, observed T1, and interaction of free and bound water in specific tissues were identified and correlated with existing physiological knowledge. Swelling of stratum corneum due to hydration was expressed as an in vivo model of tissue hydration. Conclusion: Results of the dehydration study showed that the changes due to the previous hydration of the skin are reversible for all skin layers. For both moisturisation methods (i.e. Vaseline and skin bathing), the effects of hydration and dehydration on the skin were similar. The trends of the MRI parameters for finger pad and arm skin were similar. The group study showed low inter‐subject variability of hydration on stratum corneum and epidermis.     

Clinical microneedle injection of methyl nicotinate: stratum corneum penetration

BACKGROUND/PURPOSE: In recent years, microneedles were proposed as a method to painlessly deliver drugs past the stratum corneum. Microneedles have been fabricated in several designs, but limited studies have tested microneedle injections in humans. In this work, we compare microneedle injections with topical application (TA) to investigate if microneedles enhance in vivo drug delivery past the stratum corneum. METHOD: In vitro tests were used to measure microneedle pressures and injection volumes. In vivo microneedle injections were performed on the volar forearm of 11 healthy volunteers. Two sets of microneedles, pointed and symmetric, were used to develop microneedle/syringe apparatuses that were used to inject approximately 1 microL of 0.1 M methyl nicotinate, and were compared against TA. A Laser Doppler Perfusion Monitor was used to record maximum blood flow and the time to maximum blood flow at the treatment sites. RESULTS: Pointed and symmetric microneedle-injected sites showed a significantly faster time to maximum blood flow than TA. The pointed microneedle injections also resulted in a higher maximum blood flux. Volunteers reported feeling pressure but no pain from the microneedles during the injections. CONCLUSION: The microneedles aid in bypassing the stratum corneum and enhance drug delivery through it. The design of the microneedle influences its delivery capabilities, because the pointed microneedles seem to be less susceptible to clogging during the injection.     

Hydration disrupts human stratum corneum ultrastructure

Using transmission and cryo-scanning electron microscopy, we confirm that extended water exposure leads to extensive disruption of stratum corneum intercellular lipid lamellae. We define the in vivo swelling behavior of the stratum corneum: exposure to water for 4 or 24 h results in a 3- or 4-fold expansion of the stratum corneum thickness, respectively. Corneocytes swell uniformly with the exception of the outermost and inner two to four corneocyte layers, which swell less. We show that hydration induces large pools of water in the intercellular space, pools that can exceed the size of water-swollen corneocytes. By 4 h of water exposure there are numerous small and large intercellular pools of water ("cisternae") present throughout the stratum corneum, and at 24 h these cisternae substantially increase in size. Within cisternae the lipid structure is disrupted by lamellar delamination ("roll-up"). Cisternae appear to be disk-shaped structures that do not obviously communicate. Cisternae appear to contain considerable lipidic and other material and to contain a substantial fluid volume that can rival the volume of the dry stratum corneum. Similar results are obtained following urine exposure. With urine exposure, cisternae communicate with salts in the external solution. This study illustrates the disruptive effect of overhydration on the stratum corneum intercellular space, identifies large and numerous unanticipated intercellular cisternal structures, defines the magnitude of stratum corneum swelling, and identifies stratum corneum cell layers that swell less. The study suggests the stratum corneum is a more chaotic structure than previously envisioned, and provides a framework for better understanding desquamation, irritancy, and percutaneous transport.     

Short-term glucocorticoid treatment compromises both permeability barrier homeostasis and stratum corneum integrity: inhibition of epidermal lipid synthesis accounts for functional abnormalities

Prolonged exposure of human epidermis to excess endogenous or exogenous glucocorticoids can result in well-recognized cutaneous abnormalities. Here, we determined whether short-term glucocorticoid treatment would also display adverse effects, specifically on two key epidermal functions, permeability barrier homeostasis and stratum corneum integrity and cohesion, and the basis for such changes. In humans 3 d of treatment with a potent, commonly employed topical glucocorticoid (clobetasol), applied topically, produced a deterioration in barrier homeostasis, characterized by delayed barrier recovery and abnormal stratum corneum integrity (rate of barrier disruption with tape strippings) and stratum corneum cohesion (microg protein removed per stripping). Short-term systemic and topical glucocorticoid produced similar functional defects in mice, where the basis for these abnormalities was explored further. Both the production and secretion of lamellar bodies were profoundly decreased in topical glucocorticoid-treated mice resulting in decreased extracellular lamellar bilayers. These structural changes, in turn, were attributable to a profound global inhibition of lipid synthesis, demonstrated both in epidermis and in cultured human keratinocytes. The basis for the abnormality in stratum corneum integrity and cohesion was a diminution in the density of corneodesmosomes in the lower stratum corneum. We next performed topical replacement studies to determine whether lipid deficiency accounts for the glucocorticoid-induced functional abnormalities. The abnormalities in both permeability barrier homeostasis and stratum corneum integrity were corrected by topical applications of an equimolar distribution of free fatty acids, cholesterol, and ceramides, indicating that glucocorticoid-induced inhibition of epidermal lipid synthesis accounts for the derangements in both cutaneous barrier function and stratum corneum integrity/cohesion. These studies indicate that even short-term exposure to potent glucocorticosteroids can exert profound negative effects on cutaneous structure and function. Finally, topical replenishment with epidermal physiologic lipids could represent a potential method to reduce the adverse cutaneous effects of both topical glucocorticoid treatment and Cushing's syndrome.     

Functional and structural changes of the epidermal barrier induced by various types of insults in hairless mice

Abstract Acute barrier disruption, regardless of the method of induction, depletes the stratum corneum intercellular lipids and this stimulates a series of lipid/ DNA synthesis activities which lead to barrier recovery. After barrier disruption by tape stripping, occlusion with a water vapor-impermeable membrane inhibits barrier repair. In this study, we investigated the changes in the murine epidermis after barrier perturbation by tape stripping and three different types of surfactants (Emalex NP-12, ENP-12; sodium dodecyl sulfate, SDS; benzalkonium chloride, BKC). To examine the effect of an artificial barrier, we covered the animals with a water vapor-impermeable membrane for 3 days following barrier disruption and then exposed them to the air for 2 days. The histological findings after occlusion or air exposure were similar. However, after air exposure for 2 days, the thickness of the epidermis including the stratum corneum and the stratum granulosum layers decreased to about half that of the epidermis after occlusion. Ultrastructural examination revealed obvious distortion of the lamellar bilayers within the stratum corneum interstices immediately after barrier disruption. After 3 days of occlusion, extensive disorganization was evident in the intercellular domain of the stratum corneum, whereas 2 days after removal of the occlusion, the normal basic unit structure of the lamellar bilayers had partially reappeared. Our findings provide evidence that the kinetic pattern of barrier repair and the morphological changes are similar after occlusion following barrier disruption regardless of the mechanism of disruption. Received: 14 August 2000 / Revised: 20 December 2000 / Accepted: 24 February 2001     

Properties of acid phosphatase in human stratum corneum

Sheets of stratum corneum were prepared by a trypsinization procedure from human skin samples, homogenized with a freeze press and then fractionated into a soluble fraction and a sediment by centrifugation at 50,000 g. Acid phosphatase (AcP) activity was found in both fractions but the bulk of the activity was detected in the supernatant. Highest activities were observed after treatment with Triton X-100. The bulk of the AcP activity remained bound to the pellet, if suspension and fractionation of the homogenized stratum corneum were performed in acetate buffer in the range between pH 4.0-5.0, probably due to ionic or hydrophobic interactions. AcP activity was totally lost if homogenates or fractions were stored frozen at -20 degrees C in buffers with pH values lower than 4.0. Triton X-100 extracts from whole skin, epidermis, stratum corneum, cultured skin fibroblasts and leukocytes were compared by isoelectric focusing. Extracts from whole skin, epidermis and stratum corneum yielded almost identical patterns with one main AcP activity band at pI of 5.65, whereas a second pronounced band from whole skin behaved similarly to one band from cultured skin fibroblasts and leukocytes (pI 6.1). The prominent band from extracts of stratum corneum and epidermis was not observed in extracts of skin fibroblasts and leukocytes. Hence, we conclude that stratum corneum and epidermis contain a tissue-specific AcP.     

Do we alter ultraviolet sensitivity in vivo with stratum corneum rehydration? A pilot study and review of the literature

BACKGROUND: Numerous therapeutic schemes recommend topical administration of emollients immediately prior to ultraviolet (UV) B therapy. The rationale behind the clinical improvement is a presumed enhancement of UV transmission through the epidermis. Originating from this clinical observation, there has been some concern as to whether a well-hydrated skin in general might be more susceptible to actinic damage. OBJECTIVES: To investigate whether rehydration of healthy skin causes an altered UVB sensitivity in vivo. METHODS: We determined minimal erythema doses (MEDs) and erythema sum scores (ESSs) after differential rehydration of the skin in 10 healthy volunteers. In each subject six UVB phototests were performed after pretreatment with five different emulsifying ointments (unguentum emulsificans and dilutions with 30, 50, 70 and 90% aqua purificans) plus a negative control. In vivo evaluation of stratum corneum hydration was performed by measurement of electrical capacitance. RESULTS: The results of this randomized, double-blind in vivo study indicated that rehydration of normal stratum corneum with the emulsifying ointments tested did not result in a significantly altered sensitivity to the erythematous effects of UVB irradiation (no significant differences in MED and ESS). Furthermore, there was no correlation between measured stratum corneum hydration and the erythema response of healthy skin. CONCLUSIONS: Although many schemes recommend the administration of emollients prior to UV therapy, there have also been calls for caution, as an uncritical application may interfere with such treatment. We showed that the emulsifying ointments tested exhibited no photoprotective potential and thus are suitable for the pretreatment of psoriasis prior to phototherapy. It has long been discussed whether the effects of emollient pretreatment on response to UV occur only in psoriatic skin or also in healthy skin. Our results indicated that stratum corneum rehydration did not result in a significantly increased erythema response of healthy skin to UVB exposure. With regard to the use of rehydrating cosmetics in everyday life, the outcome of our pilot study is reassuring, as we could not confirm with our experimental design that well-hydrated healthy skin is more prone to actinic damage.