Epidermis function

Stratum corneum, the outermost layer of mammalian epidermis, functions physiologically as the principal diflFusion barrier to molecules penetrating the skin and as a protective physical barrier to mechanical insults at the skin surface. Data suggest that these functions are critically dependent on the specific morphological and macromolecular organization of the membrane mosaic (16, 17, 18, 19, 20). Thus, alterations of biophysical properties arise from environmental factors acting directly on the membrane or upon the keratinization process, and they affect... 

Hydroxy vitamin D pools ia the blood and is transported on DBF to the kidney, where further hydroxylation takes place at C-1 or C-24 ia response to calcium levels. l-Hydroxylation occurs primarily ia the kidney mitochondria and is cataly2ed by a mixed-function monooxygenase with a specific cytochrome P-450 (52,179,180). 1 a- and 24-Hydroxylation of 25-hydroxycholecalciferol has also been shown to take place ia the placenta of pregnant mammals and ia bone cells, as well as ia the epidermis. Low phosphate levels also stimulate 1,25-dihydtoxycholecalciferol production, which ia turn stimulates intestinal calcium as well as phosphoms absorption. It also mobilizes these minerals from bone and decreases their kidney excretion. Together with PTH, calcitriol also stimulates renal reabsorption of the calcium and phosphoms by the proximal tubules (51,141,181—183). 

Skin functions as both, an important physical barrier to the absorption of toxic substances and simultaneously as a portal of entry of such substances. The stratum comeum of the epidermis is most significant in providing some degree of physical... 

Let us consider how the skin is structured to better understand how this tissue performs some of its vital functions. Consider the cross section of the skin sketched in Fig. 1. This illustration shows the readily distinguishable layers of the skin, from the outside of the skin inwards the 10 pm thin, fully differentiated, devitalized outer epidermal layer called the stratum corneum the 100 pm thin live, cellular epidermis and the 1000 pm thin (1 mm thin) dermis. Note that all the thicknesses specified here are representative only, for the actual thickness of each stratum varies severalfold from place to place on the body. Dispersed... 

The stratum corneum consists of separated, nonviable, cornified, almost nonpermeable corneocytes embedded into a continuous lipid bilayer made of various classes of lipids, for example, ceramides, cholesterol, cholesterol esters, free fatty acids, and triglycerides [6], Structurally, this epidermis layer is best described by the so-called brick-and-mortar model [7], The stratum corneum is crucial for the barrier function of the skin, controlling percutaneous absorption of dermally applied substances and regulating fluid homeostasis. The thickness of the stratum corneum is usually 10-25 /an, with exceptions at the soles of the feet and the palms, and swells several-fold when hydrated. All components of the stratum corneum originate from the basal layer of the epidermis, the stratum germinativum. 

Epidermis Complete removal of the dermis may be achieved by several mechanical, thermal, and chemical techniques. Most commonly, the epidermal-dermal junction is split by heating the skin to 60 C for 30-120 s [83, 84], Pitman et al. [85] could show that such a treatment does not impair the barrier function. The use of ethylene diamine tetraacetic acid, sodium bromide, or ammonia fumes has also been reported [80, 83, 86], It may, however, be suspected that the use of sufficiently strong acids or bases may change the buffer capacity of skin, which would especially influence the penetration behavior of ionizable drugs. 

The human skin model assay involves measuring the effects of corrosives on viable cells in a reconstituted human skin equivalent. To be accepted as a valid human skin model, several criteria must be met. The artificial skin must comprise a functional stratum corneum with an underlying layer of viable cells. Furthermore, the barrier function of the stratum corneum, as well as the viability of the epidermis, must be verified with appropriate experimental setups. The chemicals to be tested are applied up to 4 h as a liquid or a wet powder onto the skin model. Afterwards, careful washing has to be performed, followed by investigation of the cell viability [e.g., with a (MTT)] reduction assay). 

IL-13 on keratinocytes, two Th-2 cytokines which function via the same receptor in this cell type [26]. IL-13 or IL-4-stimulated keratinocytes attract CCR4+CD4-I- Th-2 cells via CCL22 [27]. Moreover, IL-13 induces the expression of MMP-9 in keratinocytes [28] which may play a crucial role in atopic skin inflammation by facilitating the migration of leukocytes into the epidermis. 

The EpiDerm (EPI-200) skin model is mechanistically and functionally related to EPISKIN. The assay consists of normal human epidermal keratinocytes, which have been cultured in a chemically defined medium to produce a stratified, highly diEerentiated, organotypic tissue model of the human epidermis. 

The principle of the human skin model test is that the test material is apphed topically for up to 4h to a three-dimensional human skin model, comprising at least a reconstructed epidermis with a functional stratum comeum (outermost layer of the skin). The human skin models can come from various sources, but they must meet certain criteria. Corrosive materials are identified by their abdity to produce a decrease in cell viabdity (as determined, e.g., by using a dye reduction assay) below defined threshold levels at specified exposure periods. The principle of the test is in accordance with the hypothesis that corrosive chemicals are able to penetrate the stratum comeum (by diffusion or erosion) and are sufficiently cytotoxic to cause cell death in the underlying cell layers. 

The skin not only is a barrier to restrict diffusion of chemicals into the body, it is also an organ that can metabolize a variety of topically applied substances before they become systemically available. The skin has many of the same enzymes as the liver. The activities of several cutaneous enzymes in whole skin homogenates have been measured and compared to hepatic activity in the mouse. The activities of the enzymes in the whole skin homogenates were typically 2-6% of the hepatic values. However, there is evidence that the enzymes are present primarily in the epidermis. Because the epidermis makes up only 2-3% of the total skin, the real activities may range from 80% to 240% of those in the liver. Enzyme systems present include a qrtochrome P-450 system and a mixed-function oxidase system. 

The layers of the epidermis. (Adapted with permission from Montagna W and Parakkal PR The Structure and Function of Skin [3rd ed.]. New York Academic, 1974.)... 

In addition to nutritional value and flavor, health concerns must also be a part of any discussion of food quality. Among the most interesting of food products with a health related function are the CLAs or conjugated dienoic derivatives of linoleic acid. The CLAs were originally found in meat (beef) extracts and have been shown to be a potent inhibitor of carcinogen-induced neoplasia in the epidermis and forestomach in mice and of the mammaiy in rats Chapter 21). 

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