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Hemodynamics and vascular sensitivity to circulating norepinephrine in normal skin and delayed and acute random skin flaps in the pig.

Cutaneous circulation in 4 X 10 cm skin samples and delayed and acute random skin flaps constructed on the flanks of castrated Yorkshire pigs (13.3 +/- 0.7 kg; n = 12) were studied during intravenous infusion (0.5 ml per minute) of 5% dextrose solution (vehicle) and 5% dextrose containing norepinephrine (1 microgram/kg per minute). Total and capillary blood flow and A-V shunt flow were measured by the radioactive microsphere technique 6 hours after the raising of 4 X 10 cm single-pedicle acute and delayed random skin flaps using the technique and calculations published previously. Fluorescein dye test was also performed to assess vascular perfusion. It was observed that the capillary blood flow in the single-pedicle delayed skin flaps was similar to that in the normal skin, and the maintenance of this normal skin blood flow was not due to the closing of A-V shunt flow in the delayed skin flaps. Similarly, the significant (p less than 0.01) decrease in capillary blood flow and distal perfusion in the acute skin flaps compared with the delayed skin flaps was not due to the opening of A-V shunts in the acute skin flaps. There was no evidence to indicate that A-V shunt flow per se was the primary factor for the regulation of capillary blood flow in the acute and delayed skin flaps in the pig. Our data seemed to indicate that tissue ischemia in the distal portion of acute skin flaps was likely the result of vasoconstriction of the small random arteries which supplied blood to arterioles and A-V shunts, and locally released neurohumoral substances may play an important role in the pathogenesis of vascular resistance and ischemia in the acute skin flaps.

Animals↗

Skin fails too: acute, chronic, and end-stage skin failure.

OBJECTIVE: To identify what has been published in the literature about acute and chronic skin failure and to propose a working definition of this phenomenon. DESIGN: A systematic review of MEDLINE and CINAHL to determine what has been published in the literature on the topics of skin failure, acute skin failure, chronic skin failure, multiple organ failure, end-of-life skin deterioration, and pressure ulcers in hospice from 1984 to 2005. MAIN OUTCOME MEASURES: Published papers were reviewed for content related to acute, chronic, and end-stage skin failure. MAIN RESULTS: Seven articles were identified that referenced either acute, chronic, or end-stage skin failure. Additional information was identified that discussed the processes of acute and chronic skin failure and pressure ulcers in individuals in hospice care or at the end of life. Care considerations and dilemmas related to a curative versus palliative goal in wound healing were discussed. CONCLUSIONS: Minimal literature exists on skin failure, yet caregivers and the public must be aware of, assess for, and consider this phenomenon in their care. Based on this literature review, skin failure was defined by the authors as an event in which the skin and underlying tissue die due to hypoperfusion that occurs concurrent with severe dysfunction or failure of other organ systems. Skin failure can be categorized as acute, chronic, or end stage. Pressure ulcers, a type of skin death, frequently occur in persons with a heavy disease burden, especially those at or near the end of life, despite good care.

Acute Disease↗

Limitations of hairless mouse skin as a model for in vitro permeation studies through human skin: hydration damage.

Hairless mouse skin currently provides a popular model membrane for studies in human percutaneous absorption. Although some similarities between the two skin types have been demonstrated, the effects of prolonged hydration on hairless mouse skin have not previously been rigorously examined. We have measured in vitro the effects of hydration at 31 degrees C on the permeabilities of hairless mouse skin and human abdominal and scalp skin to a model polar compound (water) and a lipid material (hexanol). The permeability of hairless mouse skin rose dramatically, especially to water (fiftyfold increase), whereas the human skin was more stable. We also compared the effects of stripping the stratum corneum with the effects of 8-d hydration for hairless mouse and human abdominal skin. Hydration of hairless mouse skin was as effective as tape-stripping in eliminating the stratum corneum barrier, whereas stripping human skin was far more damaging than hydration, suggesting that prolonged hydration mechanically disrupted mouse skin but not human skin. Histological examination of fresh and hydrated tissues confirmed this suggestion. We therefore recommend that hairless mouse skin is not used as a model for human tissue during in vitro permeation studies under conditions of long-term hydration, i.e., greater than three days.

Animals↗

Diffusion of [2-14C]diazepam across hairless mouse skin and human skin.

The objectives of this study were to investigate the absorption of diazepam applied topically to the hairless mouse in vivo and to determine the diffusion of diazepam across isolated hairless mouse skin and human skin. [14C]Diazepam was readily absorbed after topical administration to the intact hairless mouse, a total of 75.8% of the 14C-label applied being recovered in urine and feces. Diazepam was found to diffuse across human and hairless mouse skin unchanged in experiments with twin-chambered diffusion cells. The variation in diffusion rate or the flux for both human and mouse tissues was greater among specimens than between duplicate or triplicate trials for a single specimen. Fluxes for mouse skin (stratum corneum, epidermis, and dermis) were greater than for human skin (stratum corneum and epidermis): 0.35-0.61 microgram/cm2/h for mouse skin vs 0.24-0.42 microgram/cm2/h for human skin. The permeability coefficients for mouse skin ranged from 1.4-2.4 X 10(-2)cm/h compared with 0.8-1.4 X 10(-2)cm/h for human skin. Although human stratum corneum is almost twice the thickness of that of the hairless mouse, the diffusion coefficients for human skin were 3-12 times greater (0.76-3.31 X 10(-6) cm2/h for human skin vs 0.12-0.27 X 10(-6) cm2/h for hairless mouse) because of a shorter lag time for diffusion across human skin. These differences between the diffusion coefficients and diffusion rates (or permeability coefficients) suggest that the presence of the dermis may present some barrier properties. In vitro the dermis may require complete saturation before the diazepam can be detected in the receiving chamber. [14C]Diazepam was not detected in the receiving chamber of the Franz cell apparatus in experiments with human skin. This indicated that the rate of diffusion was less than 0.09 microgram/cm2/h. Since this diffusion technique more closely resembles topical administration to humans, these results appear to indicate that achieving therapeutic concentrations in humans may be difficult. In addition, the hairless mouse may not be a suitable model for predicting percutaneous absorption of diazepam in humans.

Absorption↗

Pathogenic role for skin macrophages in a mouse model of keratinocyte-induced psoriasis-like skin inflammation.

Psoriasis is a common skin disease, the pathogenesis of which has not yet been resolved. In mice, epidermis-specific deletion of inhibitor of NF-kappaB (IkappaB) kinase 2 (IKK2) results in a skin phenotype that mimics human psoriasis in several aspects. Like psoriasis, this skin disease shows pronounced improvement when mice are treated with a TNF-neutralizing agent. We have found previously that this phenotype does not depend on the presence of alphabeta T lymphocytes. In order to evaluate contributions of other immune cell populations to the skin disease, we selectively eliminated macrophages and granulocytes from the skin of mice with epidermis-specific deletion of IKK2 (K14-Cre-IKK2fl/fl mice). Elimination of skin macrophages by subcutaneous injection of clodronate liposomes was accompanied by inhibition of granulocyte migration into the skin and resulted in a dramatic attenuation of psoriasis-like skin changes. The hyperproliferative, inflammatory skin disease in K14-Cre-IKK2fl/fl mice was a direct consequence of the presence of macrophages in the skin, as targeted deletion of CD18, which prevented accumulation of granulocytes but not macrophages, did not lead to major changes in the phenotype. Targeted deletion of the receptor for IFN-gamma revealed that the pathogenesis of the skin disease does not depend on classical IFN-gamma-mediated macrophage activation. Our results demonstrate that in mice epidermal keratinocytes can initiate a hyperproliferative, inflammatory, IFN-gamma-independent, psoriasis-like skin disease whose development requires essential contributions from skin macrophages but not from granulocytes or alphabeta T lymphocytes.

Animals↗

Skin involvement in invasive breast carcinoma: safety of skin-sparing mastectomy.

BACKGROUND: There is concern about the oncological safety of preserving most of the breast skin in skin-sparing mastectomy (SSM). Most supportive evidence for SSM evaluates the local recurrence rate on clinical follow-up. METHODS: The skin and 10 mm of the subcutaneous tissue of 30 total mastectomy specimens were studied with a step-serial sectioning technique. The incidence and mode of involvement of the skin and subcutaneous tissue were recorded in detail. This was correlated with other clinical and pathologic parameters. RESULTS: The incidence of skin involvement outside the nipple-areola complex was 20% (6 of 30). This was significantly related to the clinical T stage, site of the tumor, skin tethering, pathologic tumor size, and perineural infiltration. When the effects of both skin and subcutaneous tissue involvement were considered, the incidence of skin-flap involvement outside the nipple-areola complex was 23% (7 of 30). The significant parameters related to skin-flap involvement were skin tethering (75% vs. 15%; P <.05), pathologic tumor size (P <.03), and perineural infiltration (63% vs. 9%; P <.01). CONCLUSIONS: It would be oncologically safe to perform SSM in T1 and T2 tumors, because the chance of skin involvement is small. It is safe to preserve the skin overlying the tumor if there is no skin tethering.

Adult↗

Meshed skin graft versus split thickness skin graft in diabetic ulcer coverage.

OBJECTIVE: To compare results of skin graft healing in diabetic ulcers between the meshed skin graft method and split thickness skin graft method. Duration of complete skin graft healing in both groups was recorded. The relations between ulcer size and complete skin graft healing duration were analyzed. PATIENTS AND METHOD: This research used a prospective randomized controlled study with 80 diabetic ulcer patients from January 2002-June 2003. Thirty-eight cases were treated by the meshed skin graft method with expansion ratio 1:3 and another 42 cases were treated with the ordinary split-thickness skin. RESULTS: The means of complete healing duration were 19.84 +/- 7.37 days in the meshed skin group and 20.36 +/- 7.21 days in the normal split-thickness skin graft group. There was no statistically significant difference between the groups in duration of complete graft healing and efficacy of treatment. The cosmetic result was accepted in both skin graft methods. There was no statistically significant difference between wound size and complete skin graft healing duration. CONCLUSION: The meshed skin graft method is as good for diabetic ulcer coverage as the ordinary split thickness skin graft.

Adult↗

Adverse and beneficial effects of plant extracts on skin and skin disorders.

Plants are of relevance to dermatology for both their adverse and beneficial effects on skin and skin disorders respectively. Virtually all cultures worldwide have relied historically, or continue to rely on medicinal plants for primary health care. Approximately one-third of all traditional medicines are for treatment of wounds or skin disorders, compared to only 1-3% of modern drugs. The use of such medicinal plant extracts for the treatment of skin disorders arguably has been based largely on historical/anecdotal evidence, since there has been relatively little data available in the scientific literature, particularly with regard to the efficacy of plant extracts in controlled clinical trials. In this article therefore, adverse and beneficial aspects of medicinal plants relating to skin and skin disorders have been reviewed, based on recently available information from the peer-reviewed scientific literature. Beneficial aspects of medicinal plants on skin include: healing of wounds and burn injuries (especially Aloe vera); antifungal, antiviral, antibacterial and acaricidal activity against skin infections such as acne, herpes and scabies (especially tea tree (Melaleuca alternifolia) oil); activity against inflammatory/immune disorders affecting skin (e.g. psoriasis); and anti-tumour promoting activity against skin cancer (identified using chemically-induced two-stage carcinogenesis in mice). Adverse effects of plants on skin reviewed include: irritant contact dermatitis caused mechanically (spines, irritant hairs) or by irritant chemicals in plant sap (especially members of the Ranunculaceae, Euphorbiaceae and Compositae plant families); phytophotodermatitis resulting from skin contamination by plants containing furocoumarins, and subsequent exposure to UV light (notably members of the Umbelliferae and Rutaceae plant families); and immediate (type I) or delayed hypersensitivity contact reactions mediated by the immune system in individuals sensitized to plants or plant products (e.g. peanut allergy, poison ivy (Toxicodendron) poisoning).

Burns↗

The use of the source-skin distance measuring bridge indeed reduces skin teleangiectasia after interstitial boost in breast conserving therapy.

BACKGROUND AND PURPOSE: In 1990 the skin source measuring bridge was proposed as a tool to measure (1) the distance between the interstitial implant and the overlying skin during brachytherapy boost treatment as well as (2) the distances between the lateral source end and the exit point of the guide needle. The present study reports on the clinical experience using the source skin measuring bridge with respect to incidence and grade of teleangiectasia, and their relation to source skin distances and doses. PATIENTS AND METHODS: Two hundred and twenty-two breast cancer patients (229 breasts) treated between 1983 and 1996 with breast conserving therapy including a brachytherapy boost were scored on the occurrence of teleangiectasia. The minimum distance between the sources (above implant and laterally) and the skin surface were measured. RESULTS: If no bridge was used the appearance of teleangiectasia in the epiderm above the implant is 77, 63 and 50% for boost doses of 25, 20 and 15 Gy, respectively. For brachytherapy boost doses of 25 and 20 Gy and distances smaller than 10mm between the implant and the overlying epiderm, as determined with the skin source measuring bridge, the appearance of teleangiectasia was 78 and 46%, respectively. When respecting provisional dosimetry to spare the skin for a boost dose of 15 Gy, resulting in distances between 10 and 15 mm for the implant overlying skin and distances between 5 and 10 mm for the lateral skin, teleangiectasia can be reduced to a minimum (6.3% above and 3.3% laterally). While in a univariate analysis several parameters (use of the bridge, boost dose, boost modality, external beam therapy modality) were predictive factors, the use of the bridge remained the only significant variable in a multivariate analysis. CONCLUSIONS: The skin source measuring bridge reduces teleangiectasia after interstitial brachytherapy boost treatment. A hypothesis made previously relating teleangiectasia and source skin distances was verified and extended. Even when 3D planning is used, the bridge allows for a provisional calculation of the security margins between source positions and the skin at the time of BT implantation to assure a correct needle positioning from the beginning, instead of correcting dwell times later on to avoid unnecessary high skin doses.

Adult↗

Regional specificity of anuran larval skin during metamorphosis: dermal specificity in development and histolysis of recombined skin grafts.

Skins from back and tail were dissected from tadpoles of Rana japonica prior to resorption of the tail and separated into epidermis and dermis by treatment with neutral protease. Homotypically and heterotypically recombined skins were constructed from the separated epidermis and dermis and transplanted into the tail of the original tadpole. Skin grafts using dermis from tail region degenerated simultaneously with resorption of the tail. However, skin grafts containing dermis from back region survived on the posterior part of the juvenile frog beyond metamorphosis. Furthermore, all epidermis underlaid with dermis from back region formed secretory glands and became flattened epithelia characteristic of adult back skin, regardless of region from which the epidermis came. Even when epidermis isolated from tail skin was cultured inside a back skin graft, the tail epidermis survived forming an epithelial cyst and developed secretory glands. These results suggest that regional specificities of anuran larval skin, i.e., development of back skin and even histolysis of tail skin, are determined by regionally specific dermis. The results also suggest that some of epidermal cells of tail skin are able to differentiate into epithelial cells similar to back skin of the adult under the influence of back dermis.

Animals↗

Excised porcine skin experimental systems to validate quantitative microdialysis methods for determination of drugs in skin after topical application.

Microdialysis is useful as a method to evaluate the disposition of drugs in the skin to design improved transdermal delivery systems (TDDSs). In this study, quantitative microdialysis methods were validated in excised porcine skin experimental systems in vitro. Flurbiprofen (FP), used as a model drug, showed high affinity for the skin tissues in equilibrium states between the medium and skin. The membrane clearances of FP for permeation through the membrane of a dialysis fiber placed in the skin (CL(m in S)) were lower than that in the medium. The adsorption of components in the skin to the membrane surface of the dialysis fiber and accumulation of FP near the dialysis fiber are the most likely reasons for this. When CL(m in S) was used to predict the extracellular FP concentration in skin (C(T)), the value obtained was lower than that expected from the FP concentration in the medium on the dermis side, which should be equal to C(T) at equilibrium. In the zero net flux (ZNF) method, in which the concentration difference of perfusate (DeltaC) between the inflow and outflow were used to obtain C(T), the predicted C(T) was similar to the expected value. In an in vitro skin permeation experiment, the ZNF method was used for the prediction of C(T) near the dialysis fiber. The predicted C(T) was over 10 times higher than the FP concentration in the medium on the dermis side, suggesting a concentration gradient in the dermis. Although the ZNF method is good for predicting the C(T) in skin, the mass balance has to be considered for the quantitative evaluation of the skin permeation of drugs. In this study, the effect of the mass transfer of FP from the perfusate to the skin on the cumulative amount of FP passing through the skin was relatively low because of the use of suitable solutions as perfusate. The perfusion conditions and schedules should be designed carefully for quantitative evaluations using the ZNF method. These results provide useful information for the in vivo application of quantitative microdialysis to evaluate TDDS.

Administration, Topical↗

Evaluation of autologous cultured epithelium as replacement skin after tattoo excision: correlation between skin texture and histological features.

BACKGROUND: Cultured epidermal autographs (CEAs) are currently used as a coverage treatment for burn wounds, for disfiguring burn scars involving depigmentation and in restoring the elasticity of the skin. The advantage of CEAs is that epidermal sheets prepared from small skin pieces can be enlarged sufficiently to cover large burn areas. OBJECTIVES: We examined the correlation between recovery of skin texture, and elastic fibre formation and keratinocyte differentiation (assessed by immunohistochemistry) in CEAs used as replacement skin after tattoo excision in a Japanese patient. METHODS: The tattooed skin was excised down to the deep dermal layer and then CEA was transplanted onto the patient. The skin textures were evaluated by taking replicas of the skin surface, and histological changes of filaggrin, transglutaminase, involucrin, fibrillin and elastin in the autograft skin were examined by immunohistochemistry. RESULTS: The skin texture improved with time after grafting the CEA, and appeared similar to that of normal skin at 39 months. Among keratinocyte differentiation markers, filaggrin recovered to a normal pattern at around 6 months, and transglutaminase did so at 39 months, whereas involucrin expression remained abnormal at 39 months. Fibrillin expression appeared similar to that of normal skin by 39 months, except for sparse candelabra-like structures of short fibres. Elastin expression remained at a low level throughout. CONCLUSIONS: Our results show that the recovery of skin texture after application of CEAs following tattoo excision is associated with the normalization of epidermal differentiation markers, except involucrin, and with the regeneration of elastic fibres in the dermis.

Adult↗

Toxicokinetics of tumour promoters of mouse skin. II. Metabolism of the tumour promoter 12-O-tetradecanoylphorbol-13-acetate in mouse skin and biological activities of metabolites.

The metabolism of the phorbol diester [20-3H]12-O-tetradecanoylphorbol-13-acetate [( 3H]TPA) was studied in the back skin of NMRI mice after topical administration of a single tumour-promoting dose, dp. Up to 72 h after administration most of the radioactivity recovered from the skin surface, and from the epidermis and dermis of the treated skin area was unchanged TPA, as determined by silica gel HPLC of extracts obtained from these skin fractions. The major TPA metabolite was less polar than TPA and chromatographed in the range of long-chain TPA-20-acylates. At 72 h, it accounted for about 25, 5 and 30% of total radio-activity extracted from skin surface, epidermis and dermis respectively. Of metabolites more polar than TPA, phorbol-13-acetate (PA) by far predominated over 12-O-tetradecanoylphorbol (TP) in both the epidermis and dermis, and by 72 h its relative amount was 3.9 and 2.4% in these skin fractions. Both phorbol monoesters, PA and TP, were not detected in skin surface extracts. In addition to metabolites, various autoxidation products of TPA were present in small amounts in the extracts from each of the skin fractions. The TPA-20-acylate fraction of metabolites isolated from the extracts of skin fractions at 24 h was separated further into the individual metabolites by the combined use of argentation and reversed-phase HPLC. These individual metabolites were identified by co-chromatography with authentic reference compounds. They were TPA-20-acylates carrying saturated fatty acids (16-26 carbon atoms), cis-mono-unsaturated fatty acids (16-24 carbon atoms), linoleic acid and arachidonic acid. The conjugation of TPA with long-chain fatty acids is the first example of a new route of xenobiotic metabolism in skin. When tested for irritant activity on the mouse ear, TPA-20-acylates were about one to two orders of magnitude less active than TPA. Similarly, when TPA-20-tetradecanoate was tested for tumour-promoting activity on the back skin of NMRI mice over a dose range of dp = 50-200 nmol applied twice weekly according to the computer-assisted standard protocol 16, it was found to be of only intermediate potency as compared to the highly potent tumour promoter TPA. The results of the present investigation indicate that metabolic conjugation of TPA with long-chain fatty acids to yield TPA-20-acylates is another pathway of metabolic deactivation of TPA, thus supporting the hypothesis that TPA itself is the ultimate tumour promoter in mouse skin.

Animals↗

The use of full-thickness skin grafts for the skin-abutment interface around bone-anchored hearing aids.

OBJECTIVE: To review the complication rate encountered with the use of full-thickness skin grafts to establish the skin-abutment interface around bone-anchored hearing aid implants. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Fifteen patients who underwent bone-anchored hearing aid placement over a 4-year period. INTERVENTION: Each percutaneous titanium implant and abutment was placed into the temporal bone following the standard Branemark technique. Eight procedures were performed in two stages, and seven were performed as single-stage procedures. In all cases, the skin-abutment interface was established by use of a full-thickness skin graft inset around the implant. MAIN OUTCOME MEASURES: The incidence of complications resulting in skin graft loss, time from implantation to bone-anchored hearing aid use, additional procedures for revision of the interface, and complicating medical factors in the patient population. RESULTS: Seven patients (46.7%) experienced loss of the full-thickness skin graft around the abutment. Four of these seven had complicating medical factors associated with impaired wound healing: two with diabetes mellitus, one of whom was also a smoker, and two patients who were receiving inhaled steroids for treatment of asthma. Of the seven patients who lost skin grafts, two healed by secondary intention, two underwent repeated full-thickness skin grafting, and three underwent galeal rotation flaps with split-thickness skin grafting, one of which eventually required a scalp flap. No patient experienced loss of the implant. CONCLUSION: The use of full-thickness skin grafts for establishment of the skin-abutment interface around bone-anchored hearing aid implants is associated with a high rate of graft loss. Although salvage techniques can successfully establish the interface after skin graft failure, alternative methods should be considered, especially in high-risk patients.

Adult↗

Microarray analysis of gene expression in cultured skin substitutes compared with native human skin.

Cultured skin substitutes (CSS), prepared using keratinocytes, fibroblasts, and biopolymers, can facilitate closure of massive burn wounds by increasing the availability of autologous tissue for grafting. But because they contain only two cell types, skin substitutes cannot replace all of the functions of native human skin. To better understand the physiological and molecular differences between CSS and native skin, we undertook a comprehensive analysis of gene expression in native skin, cultured keratinocytes, cultured fibroblasts, and skin substitutes using Affymetrix gene chip microarrays. Hierarchical tree clustering identified six major clusters of coordinately regulated genes, using a list of 1030 genes that were the most differentially expressed between groups. These clusters correspond to biomarker pools representing expression signatures for native skin, fibroblasts, keratinocytes, and cultured skin. The expression analysis revealed that entire clusters of genes were either up- or downregulated upon combination of fibroblasts and keratinocytes in cultured skin grafts. Further, several categories of genes were overexpressed in CSS compared with native skin, including genes associated with hyperproliferative skin or activated keratinocytes. The observed pattern of expression indicates that CSS in vitro, which display a well-differentiated epidermal layer, exhibit a hyperproliferative phenotype similar to wounded native skin.

Cluster Analysis↗

Relationship between skin phototype and MED in Korean, brown skin.

The Fitzpatrick skin classification has been a useful method to categorize cutaneous sensitivity to ultraviolet radiation (UVR), although it was based originally on responses in white skin. Because the relevance of this phototype in brown skin is in question, we investigated skin phototypes of university students by a self-reporting questionnaire and measured their MEDs in Korean, brown skin. After studying our explanation of the definition of Fitzpatrick skin types, 707 Korean university students answered the questionnaire. We then measured UVB MEDs in 156 randomly selected male students. The order of frequency of skin type was type III (55.0%), IV (29.0%), and V (12.3%) by the questionnaire, with the sun sensitive categories (types I and II) reported only for 3.7%. There was no significant difference in MEDs between types IV and V, and the mean MED of each skin type did not show a monotonic increase with increasing skin type. Subjects with MEDs of 70-90 mJ/cm2 (corresponding to the MED of skin type V, as proposed by Pathak & Fitzpatrick) represented about half or more of the subjects in all categories, even types II and III. Subjects with MEDs lower than 60 mJ/cm2 were more prevalent in types II and III compared with types IV and V. We suggest that there is at best a weak relationship between the skin types, by the Fitzpatrick method, and MEDs in Korean, brown skin.

Adult↗

Percutaneous absorption of aromatic amines in rubber industry workers: impact of impaired skin and skin barrier creams.

BACKGROUND: Several aromatic amines (AA) could cause bladder cancer and are an occupational hygiene problem in the workplace. However, little is known about the percutaneous absorption of chemicals via impaired skin and about the efficacy of skin protection measures to reduce internal exposure. AIMS: To determine the impact of skin status and of skin protection measures on the internal exposure to AA in workers manufacturing rubber products. METHODS: 51 workers occupationally exposed to aniline and o-toluidine were examined. The workplace conditions, risk factors for skin and the use of personal protective equipment were assessed by means of a self-administered questionnaire. The skin of hands and forearms was clinically examined. Exposure to aniline and o-toluidine was assessed by ambient air and biological monitoring (analyses of urine samples and of haemoglobin adducts). RESULTS: Haemoglobin-AA-adduct levels in workers with erythema (73%) were significantly higher (p<0.04) than in workers with healthy skin (mean values: aniline 1150.4 ng/l vs 951.7 ng/l, o-toluidine 417.9 ng/l vs 118.3 ng/l). The multiple linear regression analysis showed that wearing gloves significantly reduced the internal exposure. A frequent use of skin barrier creams leads to a higher internal exposure of AA (p<0.03). However, the use of skincare creams at the workplace was associated with a reduced internal exposure (p<0.03). From these findings we assume that internal exposure of the workers resulted primarily from the percutaneous uptake. CONCLUSIONS: The study demonstrates a significantly higher internal exposure to AA in workers with impaired skin compared with workers with healthy skin. Daily wearing of gloves efficiently reduced internal exposure. However, an increased use of skin barrier creams enhances the percutaneous uptake of AA. Skincare creams seem to support skin regeneration and lead to reduced percutaneous uptake.

Adult↗

Comparison of cutaneous bioavailability of cosmetic preparations containing caffeine or alpha-tocopherol applied on human skin models or human skin ex vivo at finite doses.

The use of human skin models for performing cutaneous bioavailability studies has been little investigated. For instance, only few studies have been reported on human skin models dealing with vehicle effects on percutaneous penetration. The present study aimed at evaluating the influence on caffeine's and alpha-tocopherol's cutaneous bioavailability of cosmetic vehicles such as a water-in-oil emulsion, an oil-in-water emulsion, a liposome dispersion and a hydrogel applied at finite dose using the reconstructed human skin models EpiDerm and Episkin. The results were compared with those obtained in human skin ex vivo using similar experimental conditions. It was demonstrated that the rank order of solute permeability could be correctly predicted when the preparation was applied at a finite dose in human skin models, at least when solutes with far different physicochemical properties such as caffeine and alpha-tocopherol were used. If only slight effects of cosmetic vehicle on skin bioavailability were observed in human skin ex vivo, they were less predictable using skin models. Especially, alcohol-containing vehicles seemed to behave differently in EpiDerm as well as in Episkin than on human skin ex vivo. Stratum corneum intercellular lipid composition and organization of human skin models differ to some extent from that of human stratum corneum ex vivo, which contributes to less pronounced barrier properties, together with the increased hydration of the outermost stratum corneum layers of the models. These features, as well as still unknown factors, may explain the differences observed in vehicle effects in human skin ex vivo versus human skin models.

Biological Availability↗