Acta dermato-venereologica. Supplementum最新文献

The stratum corneum is a complex biological material characterized by very low permeability to water and most other molecules. This material may be thought of as a 'porous medium' composed of impermeable and permeable regions. Intercellular lipid membranes in the stratum corneum are postulated to exist in a mixture of two phases: solid (i.e. impermeable) and liquid crystalline (permeable). The corneocyte envelope is classified as impermeable. Diffusion mechanisms of solutes within, across and between the intercellular lamellae are discussed. This model represents a refinement of previous theories about the physical structures responsible for the low observed permeability of the stratum corneum.

Developing transdermal therapeutic systems for estradiol and norethindrone acetate raised questions about the steroids penetration pathway across and retention in the skin. This paper describes the distribution of 3H-estradiol and 3H-norethindrone acetate in human stratum corneum after topical application to dermatomed skin in vitro. The study involved (a) permeation experiments to determine the steroid flux, (b) autoradiographical visualization of the steroid distribution in the same skin samples, and (c) a correlation between flux and skin distribution in time. On correlating the steroid flux with intraepidermal steroid distribution, it was concluded that both permeants were bound in the skin tissue. The steroids were preferentially located in or close to the intercellular lipids of the stratum corneum, indicating that both transport and binding occurred via this domain of the stratum corneum. This study demonstrated the importance of correlating drug flux with intraepidermal drug distribution as a function of time.

The purpose of the present manuscript is to review the chemical and physical properties of epidermal lipids and to relate these properties to the formation and function of the permeability barrier of the skin. Lipids accumulate in small organelles known as lamellar granules as epidermal keratinocytes differentiate. This lipid is extruded into the intercellular spaces where it undergoes enzymatic processing to produce a lipid mixture consisting of ceramides, cholesterol and fatty acids. This intercellular lipid is uniquely organized into a multilamellar complex that fills most of the intercellular space of the stratum corneum. The barrier properties of the stratum corneum are related to the phase behavior of the intercellular lipids. It has been proposed that a structurally unusual acylglucosylceramide is thought to be involved in assembly of the lamellar granules, and a related acylceramide may have a major influence on the organization of the lamellae in the stratum corneum.

The main function of the skin is to protect the body against exogenous substances. The skin barrier is located in the outermost layer of the skin, the stratum corneum. This layer consists of keratin enriched cells embedded in lipid lamellae. These lamellae form the main barrier for diffusion of substances through the skin. In diseased skin the barrier function is often impaired. For a full understanding of the properties of the human skin barrier, insight in the stratum corneum lipid organisation is of great importance. In this paper a short description of the lipid organisation in normal human stratum corneum will be given, after which the role the main lipid classes play in the stratum corneum lipid organisation will be described. In addition the effect of cholesterol sulfate and calcium on the lipid organisation will be discussed. Finally a new model, the "sandwich model", will be proposed that describe the localisation of the fluid phases in the stratum corneum.

To maintain a constant thickness of the stratum corneum the desquamation rate and the de novo production of corneocytes is delicately balanced. Using a plantar stratum corneum model we have obtained evidence that proteolysis is a central event in the desquamation process. A number of regulatory mechanisms for desquamation have been postulated based on our findings.

Changes in the properties of the skin barrier should have correlates in the physiological status of the differentiating epidermal cells. However, the quantitative distributions of physiologically important elements and trace elements of the skin has been a neglected area of research for lack of tools to investigate this highly differentiated tissue. With the event of the particle probes, the electron microprobe and the scanning proton microprobe, it has become possible to investigate different aspects of normal skin physiology as well as pathophysiological processes. In addition penetration profiles of allergenic metals can be demonstrated with the trace element sensitive proton probe. Future approaches to the study of skin physiology in normal and pathological conditions should incorporate other techniques including immunological and biochemical tagging of particular cells to achieve a broad basis for interpretations of data.