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The importance of the stratum corneum as the rate-limiting barrier to perceutaneous penetration has been well documented in the literature. Data have also been reported which suggest that the barrier function of this zone varies among different regions of the body. However, little attention has been given to regional variation of two morphologic parameters know to affect permeability--thickness and number of cell layers. In the present study, significant regional variation in both the mean thickness and the mean number of cell layers has been documented for four selected , sample regions of the body of a population of six adult volunteers, and for two more homogeneous subgroups separated by sex and age. While the pooled data from the total population and the pooled data from the male and female subgroups are in general agreement. It has been shown that there is also marked individual variation within a region that is characteristic and specific for each individual. The number of cell layers appears to account for the variation in thickness. [ABSTRACT FROM AUTHOR]

Under normal conditions the stratum corneum in vivo is very much less hydrated than the excised tissue routinely used in laboratory permeability experiments. As a consequence, certain quantitative predictions of skin permeability based on laboratory experiments are not applicable to many cases of clinical and practical interest. In this study a modified in vitro permeability technique was used which permitted the hydration of the stratum corneum to be maintained very close to its natural state. Penetrant molecules were applied by adding a few microliters of acetone solution to the stratum corneum surface. The acetone quickly evaporated leaving a residue of solid penetrant. The time course of penetration of the solid material through the epidermis was observed as a function of applied dose, mild hydration, and solvent contact time. Remarkably steady, uniform penetration persisting over several weeks was observed. Generally, the penetration rates were similar to those observed in vivo and increased in a similar manner upon occlusion. Diffusion through the stratum corneum rather than sorption of the solid at the surface appears to be rate limiting. [ABSTRACT FROM AUTHOR]

Most quantitative permeability data on human skin are based on studies in which water was used as the vehicle. Very little is known of the permeability of normal stratum corneum as it exists in vivo where it is considerably less hydrated. Similarly very little is known of the effect of nonaqueous solvents on the skin although they are common vehicles in topical therapy. In this study the permeation rates of a homologous series of primary alcohols (C1-C10) through skin were measured. The alcohols were applied from aqueous solutions and also as the pure liquids. The permeation behavior in the two cases is compared in terms of (1) the transport rates of the alcohols, (2) the distribution equilibrium between the tissue and vehicle, and (3) the damage to the tissue produced by the vehicle. Fick's law was found to hold as an approximation for both the aqueous and the liquid alcohol systems. Using the measured data, which include permeability and diffusion constants and tissue:vehicle partition coefficients, the diffusional resistance offered by epidermis and dermis is accurately apportioned. The overwhelming role of the stratum corneum in both the aqueous and the pure liquid systems is quantitatively confirmed. The effect of the solubility characteristics of different vehicles on skin permeability is discussed. It is shown that with the aid of a few simple principles and a knowledge of the solubility character of the vehicle, the permeation of different substances can be qualitatively predicted. [ABSTRACT FROM AUTHOR]

A comparative study was undertaken in rats, rabbits, miniature swine and man, in which the percutaneous absorption of the following compounds, labeled with 14C or 35S, were studied: haloprogin, N-acetylcysteine, cortisone, testosterone, caffeine and butter yellow. The amount of radioactivity excreted in urine for 5 days following application of the test compound to the skin was employed as the index for quantifying skin penetration. A special nonocclusive foam pad device for rabbits and miniature swine was developed to prevent artifacts resulting from transfer of drug to the urine by any route other than percutaneous absorption. The dose was 4 μg/cm² of skin surface. The excretion data obtained from the topical studies were adjusted for recovery of radioactivity following intravenous administration of the radioactive drug. The results obtained in this study indicated that skin permeability decreases in the following order: rabbit, rat, pig and man. Overall, skin of miniature swine has the closest permeability characteristics to that of human skin with this series of compounds. [ABSTRACT FROM AUTHOR]

A permeability factor extracted from guinea pig skin was partially purified by Sephadex G-50, hydroxylapatite and CM-Sephadex C-50; and its properties were studied. The factor is a heat labile protein (m.w. ca. 31,000) which gave a prolonged increase in vascular permeability after intradermal injection and its activity was slightly inhibited by soybean trypsin inhibitor (24%) and diisopropyl fluorophosphate (10%) but not by Trasylol. A heat inactivation study indicated that the increase in permeability was not due to a proteinase which was present in vasoactive fractions from CM-Sephadex C-50 eluate. Separation of the permeability factor from any esterolytic activity (α-n-Benzoyl-L-Arginine Ethyl Ester as substrate) was achieved. All available evidence indicated that the permeability factor was different from previously described endogenous vasoactive substances. [ABSTRACT FROM AUTHOR]

Compounds which are known to labilize biological membranes have been demonstrated to increase tyrosinase activity in the B-16 melanoma and newborn mouse skin. Detergents, bile acids, chlorpromazin (CPZ), neutral steroids and proteases all increase melanosomal tyrosinase activity. Digitonin (0.5%) produced approximately a five fold increase in tyrosinase activity and released 50% of the enzyme from the melanosome. CPZ (10-5M) produced a 2.7 fold increase in tyrosinase activity without releasing the enzyme from the melanosome. The CPZ-induced activition of tyrosinase was decreased by the membrane stabilizer, chloroquine and abolished by prior treatment of the melanosomes with digitonin. Alteration of the outer melanosomal membrane by digitonin and CPZ was confirmed by electron microscopy. The results suggest that the membrane surrounding the melanosome regulates the accessibility of eh substrate tyrosine to the tyrosinase molecule inside the organelle. A change in membrane permeability may be the mechanism by which certain physio-logical and pharmacological compounds control or alter pigmentation. [ABSTRACT FROM AUTHOR]

A capsule is described which can be used for the measurement of the water vapor loss of the nail with the aid of the same instrumentation that has been used for the measurement of the water vapor loss of skin. The effective area of the described capsule has been determined applying an electric analog. The specific water permeability of the nail plate appeared to be independent of nail thickness in the finger nails of a healthy volunteer. [ABSTRACT FROM AUTHOR]