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Transdermal drug delivery allows for a constant rate of drug administration and prolonged action, which can be beneficial to elderly patients who are often polymedicated. Several studies have compared dermatopharmacokinetics in the young and elderly with conflicting results. Despite the potential limitations of age-related changes in skin factors and cutaneous metabolism, marketed transdermal products generally do not report age-related differences in pharmacokinetics. This overview discusses the current data, summarizes marketed product findings and highlights the importance of further studies to evaluate age-related dermatopharmacokinetics.

Changes in the skin that occur in the elderly may put them at increased risk for altered percutaneous penetration from pharmacotherapy along with potential adverse effects. Skin factors that may have a role in age-related percutaneous penetration include blood flow, pH, skin thickness, hair and pore density, and the content and structure of proteins, glycosaminoglycans (GAGs), water, and lipids. Each factor is examined as a function of increasing age along with its potential impact on percutaneous penetration. Additionally, topical drugs that successfully overcome the barrier function of the skin can still fall victim to cutaneous metabolism, thereby producing metabolites that may have increased or decreased activity. This overview discusses the current data and highlights the importance of further studies to evaluate the impact of skin factors in age-related percutaneous penetration.

To investigate differences in response to irritation according to age and site seven young-adult and eight elderly females were exposed to 0.25% sodium lauryl sulphate (SLS) under patch-test occlusion for 24 h. Ten anatomical regions were tested: forehead, upper arm, volar and dorsal forearm, postauricular, palm, abdomen, upper back, thigh, and ankle. The skin responses were evaluated 24 h post-patch removal by visual scoring and by transepidermal water loss measurements (TEWL). Non-treated symmetrical anatomical regions served as controls. SLS induced a mild erythematous reaction on most anatomical regions except the palm and TEWL was significantly increased as compared with controls. The elderly group demonstrated significantly less susceptibility to SLS-induced irritation for most regions of the body as indicated by visual scores and TEWL measurements. In addition, evaluation of the stratum corneum water content following SLS irritation demonstrated lower responses in the old age group for most regions. The thigh had the highest reactivity and the palm the lowest, in both age groups. These data suggest that young adult skin is more sensitive to SLS than old skin and that SLS irritation varies considerably with respect to region. Moreover, objective TEWL measurements seem to be a better indicator of irritant susceptibility, especially in the elderly, than clinical evaluation by visual scoring.

To examine possible ethnic variations in perception of sensitive skin, an epidemiological survey was performed in the San Francisco area. Approximately 800 telephone interviews were conducted with women from four different ethnic groups (Afro-Americans, Asians, Euro-Americans, Hispanics; approximately 200 women per group). In addition to sensitive facial skin assessments, age and other general skin condition data were collected. 52% of the subjects identified themselves as having sensitive facial skin. There was no statistical difference between the ethnic groups in terms of sensitive skin prevalence. Nevertheless, some differences were noted between ethnic subgroups of sensitive skin. Euro-Americans were characterized by a higher skin reactivity to wind and tended to be less reactive to cosmetics. Afro-Americans presented diminished skin reactivity to most environmental factors and a lower frequency of recurring facial redness. Asians appeared to have greater skin reactivity to spicy food, to sudden changes in temperature and to wind, and tended to suffer from itching more frequently. Hispanics presented a lower incidence of skin reactivity to alcohol. The differences in skin sensitivity between ethnic groups concerned mostly factors of skin reactivity and, to a lesser extent, its symptomatology. But, taken together, we note the similarities in comparing how women of varying ethnic backgrounds perceive the sensitive skin condition.

Acute irritant contact dermatitis (ICD) is frequently treated with cool water or saline compresses. While presumed effective, little quantitative evaluation documents the treatment's benefit. This study sought to determine the efficacy of both distilled water and physiologic saline compresses on experimentally-induced ICD. 24-h application of both the lipophilic nonanoic acid (NAA) and the hydrophilic sodium lauryl sulfate (SLS) were used to induce irritant contact dermatitis in 9 healthy volunteers. Following irritation, compresses were applied 0.5 h 2x daily for 4 consecutive days. Transepidermal water loss (TEWL), laser Doppler flowmetry (LDF), chromametry and visual scoring were used to quantify results. Cool compresses of both water and saline significantly reduced TEWL and LDF, with no statistically significant difference between the efficacy of the saline or water compresses. Chromametry and visual scoring did not detect a significant effect with either the water or saline compresses. The results suggest an improvement with 2x-daily application of either water or physiologic saline compresses in the treatment of acute ICD, though true clinical benefit will be elucidated through further experimentation. Certainly, the current recommendation regarding the use of cool compresses for treating ICD should not be discarded.

Tape stripping of human stratum corneum has been performed to measure stratum corneum mass, barrier function, drug reservoir and percutaneous penetration. However, the technique itself requires further development to facilitate interpretation.In this study we quantified stratum comeum (SC) tape stripping and water kinetic parameters utilizing three types of adhesive tapes, in an in vivo randomized clinical trial. Stratum corneum was tape stripped, and the mass of SC removed by each tape was quantified utilizing a protein assay. Transepidermal water loss (TEWL) was measured and barrier disruption and SC water kinetics calculated. Three commonly utilized acrylate adhesive tapes were utilized and a comparison made between them.Each type of tape successfully stripped the stratum corneum, but the rayon tape did not induce SC barrier disruption. Neither the type of tape nor the site stripped significantly influenced the mass of SC removed. Water kinetic parameters did not differ significantly for the tapes that did induce barrier disruption. Individual variation in barrier disruption to water following tape stripping was demonstrated.The tapes utilized removed a similar amount of SC. The tapes have a different propensity to cause barrier disruption. Some individuals do not demonstrate increased TEWL despite an equivalent mass of SC being removed compared to those who do show a response.

Occlusion, widely used to enhance percutaneous absorption of drugs, also increases penetration of other chemicals and antigens, and hence may exacerbate irritant and allergic contact dermatitis. This overview summarizes the adverse effects of occlusion.

Corticoid allergic contact dermatitis (ACD) may be topically or systemically elicited. Allergic contact dermatitis to topical corticosteroids is relatively common, whereas reports of orally elicited ACD to corticosteroids are rarer. Patients allergic to one corticosteroid often exhibit cross-reactivity to other corticoids. We have previously reported a 46-year-old woman with contact allergy documented by patch and provocative use testing to multiple topical corticosteroids. On further testing, she was thought to have multiple corticoid orally elicited ACD to triamcinolone, methyl prednisolone, dexamethasone, and prednisone. Oral provocation tests were performed in a single-blind fashion following the method of Alanko and Kauppinen [Diagnosis of drug eruptions: clinical evaluation and drug challenges. In, Skin Reactions to Drugs (Kauppinen K, Alanko K, Hannuksela M, Maibach HI, eds). Boca Raton, FL, CRC Press, 1998.]. The five oral corticosteroids tested were triamcinolone, methyl prednisolone, dexamethasone, prednisone, and hydrocortisone. Four of the five challenged corticosteroids (i.e., triamcinolone, methyl prednisolone, dexamethasone, and prednisone) produced a generalized maculopapular eruption in a delayed manner. The fifth challenged corticoid, hydrocortisone, had no adverse effect on this patient. This patient was unusual in that she exhibited polysensitivity to a spectrum of oral and topical corticosteroids. Hydrocortisone was identified as a corticosteroid for future clinical use. This is an important finding since corticosteroids are important emergency drugs.

To avoid the acute irritation and dryness that a single occlusive surfactant application (24-h patch test) may cause, and to approximate clinical use, an open application model was chosen to define subclinical non-erythematous irritation in the stratum corneum. This human test combined a supervised washing at the laboratory with at-home use of the test products by the subjects. Effects of washing with the surfactants on the dorsal hand and volar forearm were compared. The results demonstrated that this situational use model permits the exploration of subclinical surfactant-induced irritation. The forearm appeared to be more discriminative as compared to the dorsal hand. Squamometry proved to be a sensitive, complementary assessment method for detecting surfactant-induced subclinical skin surface alterations and for differentiating surfactant effects in this open assay.

Hyaluronic acid (HA), a high molecular weight glycosaminoglycan of the extracellular matrix involved in growth, inflammation and wound healing, also contributes to the hydration and plastic properties of skin. Several drug and cosmetic formulations contain HA. We have initiated investigations that explore whether it is possible, by topical application, to modulate endogenous HA levels in skin. We developed a model epidermal culture system that exhibited a differentiated stratum corneum, and expressed HA and the HA receptor CD44, in a pattern similar to that observed in intact skin. Such in vitro skin equivalents are useful models for investigating the effect of topical drugs. HA and bacterial hyaluronidase were applied to the in vitro skin equivalent and to human skin. Their effects on endogenous HA and CD44 expression were examined using histochemical analysis. Topical HA treatment had no significant effect on HA or CD44 expression in either system. However, hyaluronidase decreased HA and CD44 expression in a dose-dependent manner in both the epidermal culture system and in skin. Apparently, HA is not able to permeate the epidermal culture system or human skin to a significant degree, but bacterial hyaluronidase does permeate both human skin and the culture system, depleting HA and decreasing CD44 expression. These effects were more prominent in the dermal than in the epidermal layers, suggesting that marked differences in HA metabolism exist in these two skin compartments. The ability of hyaluronidase to permeate the stratum corneum suggests that topical application may, additionally, be useful as a clinical modality.

Skin care products are complex formulations that may cause sensory irritation symptoms, characterized by stinging, burning, and itching. Substances capable of counteracting sensory irritation are of great practical interest. Strontium salts have been demonstrated to inhibit sensory irritation and inflammation when applied topically. In this double-blind study, we evaluated the efficacy of strontium nitrate in reducing chemically-induced skin sensory irritation in 8 subjects. In a random order, 20% strontium nitrate in 70% glycolic acid (pH=0.6) (mixture) was applied to the volar aspect of the forearm and a positive control (70% glycolic acid, pH=0.6) to the contralateral forearm. The irritation sensation was evaluated each min for the first 20 min after topical application using a scale from 0-4. The duration of the irritation sensation in min was also recorded. Strontium nitrate mixed with glycolic acid, in comparison with glycolic acid alone, markedly (p0.01) shortened the duration of the irritation sensation from 24.4+/-4.1 (mean+/-SEM) min to 8.9+/-3.7 (mean+/-SEM) min, and significantly (p0.05) reduced the mean magnitude of the irritation sensation at all time points (overall). The study demonstrated that strontium nitrate potently suppresses the sensation of chemically-induced irritation.

False-negative patch tests are clinically relevant. Skin hyporeactivity has been suggested as one possible cause. Evidence supports that failure to respond to a specific antigen might be due either to a faulty immune response, a defective inflammatory response or both. Thus, skin hyporeactivity may have clinical relevance in routine patch testing. Articles on this topic are infrequent and there is no index keyword for skin hyporeactivity as this phenomenon is poorly defined and investigated. This article summarizes several observations of skin hyporeactivity, reviews theories of possible mechanisms and discusses further consequences.

The primary objective of this study was to determine the rate and extent of transdermal absorption for systemic delivery of diclofenac from Pennsaid (Dimethaid Research, Inc.) topical lotion into the systemic circulation after the lotion was applied to human volunteers, in an open treatment, non-blinded, non-vehicle controlled study. In addition, the in vivo metabolism of this topical diclofenac lotion has also been studied.Human volunteers were dosed with topical [14C]-diclofenac sodium 1.5% lotion on the knee for 24 h. Sequential time blood and urine samples were taken to determine pharmacokinetics, bioavailability and metabolism.Topical absorption was 6.6% of applied dose. Peak plasma 14C occurred at 30 h after dosing, and peak urinary 14C excretion was at 24-48 h. The urinary 14C excretion pattern exhibits more elimination towards 24 h and beyond, as opposed to early urinary 14C excretion. This suggests a continuous delivery of [14C]-diclofenac sodium from the lotion into and through skin which only ceased when the dosing site was washed. Skin surface residue at 24 h was 26 +/- 9.5% dose (remainder assumed lost to clothing and bedding). Extraction of metabolites from urine amounted to 7.4-22.7% in untreated urine, suggesting substantial diclofenac metabolism to more water soluble metabolites, probably conjugates, which could not be extracted by the method employed. Two Dimensional TLC analysis of untreated urine showed minimal or no diclofenac, again emphasizing the extensive in vivo metabolism of this drug. Treatment of the same urine samples with the enzymes sulfatase and beta-glucuronidase showed a substantial increase in the extractable material. Three spots were consistently present in each sample run, namely diclofenac, 3'hydroxy diclofenac and an intermediate polar metabolite (probably a hydroxylated metabolite). Therefore, there was significant sulfation and glucuronidation of both diclofenac and numerous hydroxy metabolites of diclofenac, but many of the metabolites/conjugates remain unidentified. CONCLUSIONS; There was a continuous delivery of diclofenac sodium from the lotion into and through the skin, which ceased after the dosing site was washed. The majority of the material excreted in the urine were conjugates of hydroxylated metabolites, and not the parent chemical, although further identification is required.

This study determines comparative bioavailability of diclofenac sodium lotion compared to an aqueous solution after topical application to viable human skin in vitro. In addition, the difference between a single dose and multiple doses (8 times) was also determined.An in vitro flow-through diffusion cell system was employed, using radiolabelled diclofenac sodium.Multiple doses of lotion (2 microl/cm2 and 5 microl/cm2) delivered a total of 40.1 +/- 17.6 microg and 85.6 micro 41.4 microg diclofenac, respectively, at 48 h, compared to only 9.4 +/- 2.9 microg and 35.7 +/- 19.0 microg absorbed after topical application of diclofenac as an aqueous solution (P0.05). A single dose study showed no statistical difference between diclofenac delivered in lotion or an aqueous solution. Over 48 h the total absorption from lotion was 10.2 +/- 6.7 microg and 26.2 +/- 17.6 microg (2 microl/cm2 and 5 microl/cm2, respectively), compared to 8.3 +/- 1.5 microg and 12.5 +/- 5.7 microg from an aqueous solution. Both single doses of lotion and aqueous diclofenac showed decreased diclofenac absorption into the receptor fluid between 12 and 24 h. However, when applied multiple times, absorption from lotion was continually increasing up to 48 h. The total dose accountability ranged from 76.8 +/- 8.2% to 110.6 +/- 15. 1% of the applied dose.Diclofenac lotion exhibited enhanced diclofenac percutaneous absorption rate through human skin (mass, flux and partition coefficient) when applied a multiple number of times and this enhanced absorption was maintained over 48 h. This suggests that a constituent of the lotion (DMSO) will enhance human skin absorption of diclofenac when used in a multi-dose regimen, but not after a single dose.

The efficacy of a topical agent in barrier recovery was evaluated after acetone-induced acute water loss barrier disruption in vivo in humans. The upper back of several volunteers was rubbed with acetone-soaked cotton balls until elevated rates of transepidermal water loss (TEWL) occurred (20 g/m2h, or greater). The topical agent was then applied to the acetone-treated skin sites once daily for 5 days. Resolution evaluation used TEWL measurements and the data were expressed as the percentage recovery in water barrier function. In comparison with placebo control the topical agent significantly enhanced barrier recovery, especially within the first 72 h (P0.05). This model offers a simple method of examining chemicals accelerating (or inhibiting) repair of this form of acute skin damage in man.

To evaluate skin penetration of various vitamin E homologs, a 5% solution of either alpha-tocopherol, alpha-tocotrienol, or gamma-tocotrienol in polyethylene glycol was topically applied to SKH-1 hairless mice. After 0.5, 1, 2, or 4 h (n = four per time point and four per vitamin E homolog), the skin was washed, the animals killed, the skin rapidly removed, frozen on dry ice, and a biopsy taken and sectioned: stratum corneum (two uppermost, 5-micron sections--SC1 and SC2), epidermis (next two 10-micron sections--E1 and E2), papillary dermis (next 100 microns, PD), dermis (next 400 microns, D), and subcutaneous fat (next 100 microns, SF). SC1 contained the highest vitamin E concentrations per mu thickness. To compare the distribution of the various vitamin E forms into the skin layers, the percentage of each form was expressed per its respective total. Most surprising was that the largest fraction of skin vitamin E following topical application was found in the deeper subcutaneous layers--the lowest layers, PD (40 +/- 15%) and D (36 +/- 15%), contained the major portion of the applied vitamin E forms. Although PD only represents about 16% of the total skin thickness, it contains sebaceous glands--lipid secretory organs, and, thus, may account for the vitamin E affinity for this layer. Hence, applied vitamin E penetrates rapidly through the skin, but the highest concentrations are found in the uppermost 5 microns.

Benzoic acid (BA) was used to induce nonimmunologic contact irritation in 10 younger (23-47 years old) and 5 older (72-90 years old) healthy volunteers. BA 2.5% in petrolatum was applied to 8 locations on the face, neck and volar forearm. Changes in the skin blood flow were monitored using a laser Doppler flowmeter. Also measured at each location were baseline measurements of skin blood flow, transepidermal water loss, stratum corneum hydration, skin surface temperature and skin surface pH.The neck area exhibited the greatest reaction in both age groups while the forearm exhibited the least. At each site tested, the younger group consistently demonstrated greater reactivity to BA. A significant correlation was noted between stratum corneum hydration and irritation.This information provides a basis to further study the frequent poorly understood intolerance of the face to topical formulation.

Different reactivities of small blood vessels to the histamine released by exogenous and endogenous substances may play a role in the regional variations of the elicited cutaneous response. To study the regional dependence of cutaneous blood flow in response to histamine, the compound was administered intradermally (prick introduction), thereby bypassing the spatially dependent penetration process. The induced response was quantified with cutaneous blood flow measurements utilizing laser Doppler flowmetry. Extent of response and time parameters were compared. Three anatomical sites, the back, volar side of the forearm, and ankle, were studied on 20 volunteers (10 men and 10 women, age 24-34). For comparison, topical administration was also performed. Significant differences in the measured responses at the three sites were observed: the increase of the cutaneous blood flow on the back was greater than the forearm (p0.01 prick test, p0.05 topical application), and that of both sites was greater than the ankle (p0.01 prick test, p0.05 topical application). There were no significant differences among the different sites in time parameters and no gender variations. As expected, the time required to reach maximum response was shorter for the intradermal method as compared to the topical application on the back (p0.001) and forearm (p0.05). On the other hand, the time required to decrease to 50% of maximum response was not different for the intradermal and topical methods of histamine application. These blood vessel response observations may provide initial insight into inherent functional differences influencing cutaneous manifestations of endogenous and exogenous diseases.

Four cases of contact leukoderma associated with the application of hair rinses and permanent and semipermanent hair colors are described. To our knowledge, this association has not been previously reported. Although none had evidence of pigment loss in other sites, Koebner-induced vitiligo cannot be excluded. In our cases hair color ingredients seem to have had a selective toxic effect on melanocytes. Further study of pigment loss from hair colors is warranted, especially in animal and in vitro assays. Patch testing with putative depigmenting agents in patients should be done with caution, so as to minimize potential for depigmentation in cosmetically important anatomic sites.

Skin barrier disruption caused by organic solvents to human cadaver dermatomed skin was evaluated using an in vitro model system. Resultant changes in transepidermal water loss (TEWL), as measured with an evaporimeter, were recorded after topical application of either acetone, chloroform: methanol 2: 1, hexane, hexane : methanol 2 : 3, or the control, water, for exposure times of 1,3,6, and 12 mm. The resultant lipid/solvent mixture was removed and analyzed for its lipid content. The ability of the different solvents to induce changes in the skin's barrier function was assessed by comparing pre- to post-solvent exposure TEWL (ΔTEWL).When compared to the controls, water and unexposed skin, chloroform: methanol 2: 1 caused the greatest significant increase in TEWL, followed by hexane: methanol 2: 3. Acetone and hexane showed no difference in TEWL from the controls. Besides solvent, exposure time was a significant independent variable for predicting ΔTEWL, and the interaction of the two (exposure time and solvent type together) was the strongest predictor.Lipid analysis of the extracts revealed that all the solvents removed comparable quantities of the surface lipids (tri-glycerides, wax esters, squalene, cholesterol esters). Stratum corneum lipids—ceramides, free fatty acids, and cholesterol—extracted by chloroform : methanol 2: 1 and hexane: methanol 2: 3 were comparable and significantly greater than those extracted by acetone and hexane. These two solvents failed, however, to induce comparable changes in TEWL, as chloroform : methanol 2: 1 induced a significantly greater ATEWL than hexane: methanol 2:3. Additionally, no individual lipid class extracted by either chloroform : methanol 2: 1 or hexane : methanol 2: 3 proved to be a significant or accurate variable for predicting ΔTEWL. This suggests that the mechanism by which topical chloroform : methanol 2 : 1 and hexane : methanol 2: 3 exposure induce a ΔTEWL involves more than pure lipid extraction.

Acitretin has recently been introduced for the systemic treatment of dermatologic diseases such as psoriasis and congenital disorders of keratinization. At present, only an oral form of this drug is available. However results from recent studies have shown that considerable drug concentrations can be delivered to the skin by topical administration of acitretin. Based on this data we addressed the question whether the topical administration of acitretin can produce in humans a drug concentration in the skin which exceeds the drug concentration that is found in the skin after multiple oral acitretin dosing and is reported to be clinical effective. Drug concentrations in the skin were investigated under conditions in which the maximum dose that can be administered in a therapeutic situation was applied. Additionally, three different skin sampling techniques, the punch biopsy, the shave biopsy and the suction blister technique were validated to quantitate acitretin in the skin. The drug concentrations in skin after systemic application in a steady state situation were comparable with the drug concentration reached after a single 24 hours topical application of a saturated acitretin/isopropylmyristate formulation. However, no unequivocal effects in psoriasis and disorders of keratinization were observed up to now by the topical administration of acitretin. The inverse drug concentration gradients which are present in the skin, depending on the route of administration, may explain differences in activity. The skin samples in our and other studies were homogenized or dissolved and thus much of the anatomical information is lost. The latter may be most important for the understanding of the local events.

Prick test reactions are evaluated and quantified, comparing visual assessment with two non-invasive techniques: remittance spectroscopy and pulsed ultrasound for erythema and skin thickness measurements. Different information is provided by the two methods. Remittance spectroscopy discriminates well between negative and positive reactions (+ or ++), while failing to differentiate stronger reactions, where edema is a prominent feature. The latter reactions are better evaluated by skin thickness measurements, which, on the contrary, are less sensitive in revealing small skin thickness increases in weak reactions.

Mechanical trauma to genital skin may favor the transmission of sexually transmitted diseases. To study differences between vulvar and forearm skin in epidermal repair after standardized trauma, transepidermal water loss, capacitance and pH of forearm and vulvar skin in 10 healthy premenopausal women were monitored for 7 days after a standardized trauma induced by tape stripping to glistening. Vulvar and forearm skin showed similar responses immediately after tape stripping: a sudden increase in transepidermal water loss and capacitance. Forearm skin, however, reacted more intensely than vulvar skin; forearm skin readings remained significantly higher than normal values for 2 days after tape stripping, whereas vulvar skin readings were not significantly different from normal. Thus, vulvar skin did not respond as extensively as forearm skin, presumably because it is a less complete barrier against excess body water loss. On the other hand, vulvar skin seemed to recover faster from skin damage than forearm skin, probably because of its higher epidermal cell turnover.

Laser doppler velocimetry (LDV) has been used to assess the cutaneous pharmacodynamics of isosorbide dinitrate (ISDN) following transdermal delivery of the drug from prototypal patches. The delivery systems, which were saturated with ISDN, (a) produced various degrees of skin occlusion and (b) spanned a six-fold range of adhesiveness. The patches were applied to the ventral forearm skin of 10 healthy volunteers and the local ISDN-induced increase in local skin blood flow was determined using LDV by locating the probe in a central hole in the delivery system. Measurements were made for 1.5 hr and the pharmacodynamics were quantified by (i) the maximum LDV response and (ii) the area under the LDV response versus time curve. These parameters were not sensitive to patch occlusivity. They were significantly (P less than 0.01) dependent on patch adhesiveness, though, and decreased with increasing adhesion. Although this observation suggested that ISDN diffusion through the adhesive could determine, at least in part, the rate of drug delivery, it was subsequently demonstrated that ISDN release (in vitro, into a perfect "sink") was unaffected by the level of cross-linking in the adhesive polymer. Because the drug was present in all systems at unit thermodynamic activity, these results cannot be explained on the basis of altered ISDN partitioning at the device-stratum corneum interface. We speculate that the in vivo-in vitro discrepancy may be due to the efficiency of skin contact achieved by different adhesives: that is, the more adhesive, less flexible systems make poorer contact with the skin surface, thereby decreasing the effective surface area of drug delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Human vulvar skin is an example of specialized skin. This is not only true for its gross and microscopic anatomy and physiology, but also for its microbiology. To the microbiologist, the vulva consists of several distinct ecotopes. These are defined by the physical factors, especially occlusion, nutrient factors, and by the close proximity to the vagina, the urethra, and the anus, which may result in contamination with the flora typical for those sites. Of the vulva ecotopes, only the labia majora have been seriously studied. The microbial flora of the labia majora is characterized by a high density of microorganisms, as is typical for occluded areas of the body, by the presence of organisms common for intertriginous skin such as gram-negative rods, and by the carriage of organisms unique for the vulva and probably related to urethral and vaginal flora such as the nonpathogenic neisseria, lactobacilli, and Gardnerella vaginalis. Finally, the labia majora skin is a preferred site of Staphylococcus aureus carriage that can be of clinical and epidemiological relevance.

The objective was to determine percutaneous absorption of DDT and benzo[a]pyrene in vitro and in vivo from soil into and through skin. Soil (Yolo County 65-California-57-8; 26% sand, 26% clay, 48% silt) was passed through 10-, 20-, and 48-mesh sieves. Soil then retained by 80-mesh was mixed with [14C]-labeled chemical at 10 ppm. Acetone solutions at 10 ppm were prepared for comparative analysis. Human cadaver skin was dermatomed to 500 microns and used in glass diffusion cells with human plasma as the receptor fluid (3 ml/hr flow rate) for a 24-hr skin application time. With acetone vehicle, DDT (18.1 +/- 13.4%) readily penetrated into human skin. Significantly less DDT (1.0 +/- 0.7%) penetrated into human skin from soil. DDT would not partition from human skin into human plasma in the receptor phase (less than 0.1%). With acetone vehicle, benzo[a]pyrene (23.7 +/- 9.7%) readily penetrated into human skin. Significantly less benzo[a]pyrene (1.4 +/- 0.9%) penetrated into human skin from soil. Benzo[a]pyrene would not partition from human skin into human plasma in the receptor phase (less than 0.1%). Substantivity (skin retention) was investigated by applying 14C-labeled chemical to human skin in vitro for only 25 min. After soap and water wash, 16.7 +/- 13.2% of DDT applied in acetone remained absorbed to skin. With soil only 0.25 +/- 0.11% of DDT remained absorbed to skin. After soap and water wash 5.1 +/- 2.1% of benzo[a]pyrene applied in acetone remained absorbed to skin. With soil only 0.14 +/- 0.13% of benzo[a]pyrene remained absorbed to skin.(ABSTRACT TRUNCATED AT 250 WORDS)

The functional role of different layers of the horny layer in preventing evaporative water loss was studied by an adhesive cellophane-tape stripping technique. The increase in transepidermal water loss, as described by a mathematical equation based on curve-fitting analysis, was shown to be proportional to the decrease in thickness of the horny layer. In the second half of the curve the experimental data showed slightly higher transepidermal-water-loss values than would be expected on the basis of proportionality with thickness of the stratum corneum. The data suggest that the outer layers of the horny layer are also important in forming a barrier to evaporative water loss.

Skin-surface water loss (SSWL) and transepidermal water loss (TEWL) were studied after a plastic occlusion stress test (POST) in visually non-damaged skin treated with 7% sodium lauryl sulphate for 3 days (open application). After removal of the 24-h plastic occlusion, SSWL and TEWL were recorded continuously for 25 min. SSWL decay curves show significant differences between control and treated areas. The total amount of water trapped within the stratum corneum and released after 1 min is significantly reduced (P less than 0.01) in the treated site. Higher TEWL (P less than 0.02) in visually non-irritated skin is noticeable in the terminal part of the curve reflecting the damage of the water barrier in irritated skin. The data suggest that clinically normal skin exposed to subliminal irritant stimuli is less capable of storing water within the stratum corneum resulting in decreased hydration. The POST appears to be a simple and reliable tool to investigate non-visible but biologically relevant changes in stratum corneum function.

Transepidermal water loss (TEWL) and water content of the stratum corneum, when measured simultaneously, provide important information regarding skin function. On the basis of the model presented, it is possible to differentiate dry senile skin from dry pathological skin (such as psoriasis, atopic dermatitis, irritant reaction), clinically involved or uninvolved. Pathological dry skin, because of the impaired barrier function is associated with increased TEWL and low corneum water content. Senile skin, on the other hand, shows both, decreased TEWL and stratum corneum water content. It is suggested that with this model it may be possible to differentiate uninvolved pathologic from healthy skin.

In experimental skin toxicology, as well as in clinical practice, considerable interindividual variation in the susceptibility to irritant dermatitis is noted when irritant doses are low. Cutaneous sensitivity and hypersensitivity are not determined by a single known feature but are multifactorial. Previous atopic dermatitis may predispose to irritant dermatitis. Susceptibility to irritation seems to be influenced by age, race, and genetic background, whereas sex-related differences do not seem to exist. Of biophysical skin baseline features, skin-surface pH was correlated with the severity of experimentally induced irritant dermatitis, but baseline transepidermal water loss, water-holding capacity, stratum corneum turnover time, and sebum content were not.

This study evaluated the vasodilation induced in young whites and blacks by topical application of two nicotinates, methylnicotinate (MN) and hexylnicotinate (HN) at the same concentration and in the same vehicle. To assess the influence of skin surface lipids and water content of the stratum corneum on the penetration of the substances, the drugs were applied on the back, on untreated skin and pre-occluded and pre-delipidized sites. Skin blood flow was monitored with laser Doppler velocimetry. The initial response recorded at 15 min (IR), the peak response (PR) and the area under the curve (AUC) were used to characterize the pharmacodynamic response. Statistically significant racial differences in the penetration of nicotinates were detected for the area under the response curve in the untreated and occluded sites, for the initial response and peak response in the pre-occluded site. Occlusion increased (even though not significantly) penetration, except for blacks in the methylnicotinate experiment. Delipidization elicited significantly lower responses for the IR and PR in the MN study, rendering the penetration similar in the two groups. No major differences were recorded between the two nicotinates. The effect of delipidization was most noticeable in blacks in the MN study. We suggest that there are racial (blacks vs. whites) differences in percutaneous penetration of nicotinates, with decreased levels in black skin recorded in all sites investigated.

The postocclusive hyperaemic reaction before and after a single 1 h application of a potent corticoid (clobetasol 0.05% in ointment) was recorded by means of laser Doppler velocimetry in order to elucidate different racial responses in skin vasoconstriction. Fourteen young male subjects entered the study (eight Caucasians, six Blacks). Reactive hyperaemia was recorded after 4 min of occlusion of the forearm blood flow. The following parameters of the hyperaemic reaction were investigated: area under the curve response, peak response, rise of blood flow slope to peak and decay of blood flow slope after peak. Different responses were recorded in the Black subjects after the vasoconstrictive stimulus compared to the Caucasians, namely: decreased area under the curve response (P less than 0.04); decreased peak response (P less than 0.01); decreased decay slope after peak blood flow (P less than 0.04). These data are consistent with a different reactivity of blood vessels in black skin and possibly not related to the transcutaneous penetration of the chemical compound.

This investigation demonstrates the capacity of Pityrosporum orbiculare to adhere to human stratum corneum cells in vitro; this may be an important initial step in its colonization of stratum corneum. Adherence was significantly higher when incubation for 120 min (mean 9.4 adherent yeasts) was compared to 60 min (mean 3.5 adherent yeasts, P less than 0.001), but not to 90 min (mean 8.6 adherent yeasts, P greater than 0.05). Adherence was higher at an incubation temperature of 37 degrees C (mean 10.0 adherent yeasts) as compared with 25 degrees C (mean 4.0, P less than 0.001), but not at 32 degrees C (mean 8.0, P greater than 0.1). There was no significant difference in adherence related to the anatomic area (forearm, back, and chest) from which the stratum corneum cells have been collected. No difference was seen in adherence between different Pityrosporum strains, but it increased significantly with inoculum size of P. orbiculare, being optimal at 10(7) cells ml-1. The adherence of P. orbiculare and Staphylococcus epidermidis to stratum corneum cells was not influenced by incubation of the organisms together or alone. This model opens possibilities to study the influence of: stratum corneum cells from diseased skin compared with controls; antibodies; and types of surface receptors and antimycotics on P. orbiculare adherence to stratum corneum cells.

A 4-week open cumulative irritancy test in guinea pigs discriminated between two low grade irritant vehicles, nonionic base (anhydrous) and hydrophilic ointment. The procedure might be useful as a predictive test for low grade irritants. The angry skin syndrome was established in the guinea pigs by one Freunds complete adjuvant intradermal injection on day 0, or by daily open applications of 10% sodium lauryl sulfate in petrolatum to the neck area of the animals.

The effect of skin delipidization in humans on the percutaneous penetration of hydrocortisone was investigated in a cross-over trial. The delipidizing agent was 1:1:1 trichloroethane, a common industrial organic solvent. The findings do not show any significant difference in the topical absorption of hydrocortisone with and without skin delipidization. It was postulated that the natural skin barrier was reestablished by the metabolic cutaneous lipid regeneration concomitant with the absorption of the fatty ingredients from the cream.

No abstract available

Human repeated insult patch testing with an experimental pump spray antiperspirant formulation elicited sensitization reactions in two separate groups of panelists. After several rechallenges with variations of the formula components, isostearyl alcohol at 5% concentration in the product emerged as the causative agent in both groups. Due to the high content of alcohol in the pump spray antiperspirant, control patch testing was done with 100% ethanol, which served as the vehicle for testing isostearyl alcohol alone. All reactions were negative. Six out of 148 participants in the first group and one of 60 in the second group exhibited sensitization responses to isostearyl alcohol.

This study elaborates on the effect of occlusive, partially occlusive, and nonocclusive tape systems containing hydrocoritsone on human epidermal mitotic activity that has been increased by tape stripping. The experimental variables included tape delivery systems affording total, partial (50%), or no occlusion to normal human skin. The test corticosteroid was hydrocortisone at a dose range of 1, 4, and 20 microgram/sq cm. Utilizing demecolcine cream, biopsy specimens, were taken and mitotic figures determined. Results suggest that potent antimitotic effects occur equally with semiocclusive and nonocclusive tapes containing hydrocortisone as with total occlusive tapes. Verification of the practicality of this in clinical use will depend on appropriate clinical trials in diseased states.

The effect of occlusion on the carbon dioxide (CO2) emission rate (CDER) of human skin was determined. Occlusive plastic tape elevated the CDER 4.5 times (90nl/cm2/hr) over the normal CDER (20nl/cm2/hr). This increase was noted within a 3-hour period. Non-occlusive paper tape had no effect on CDER. Quantitation of the amount of CO2 under plastic tape revealed that CO2 was present at a concentration of 8-10%. Removal of the plastic tape after 24 hours allowed the CDER to return to approximately normal values within 2 hours. The mechanism by which occlusive plastic tape mediates this dramatic effect on CDER as well as the significance of elevated CO2 concentrations under occlusion are discussed.