Epidermal production

Emulsion components enter the stratum corneum and other epidermal layers at different rates. Most of the water evaporates, and a residue of emulsifiers, Hpids, and other nonvolatile constituents remains on the skin. Some of these materials and other product ingredients may permeate the skin others remain on the surface. If the blend of nonvolatiles materially reduces the evaporative loss of water from the skin, known as the transepidermal water loss (TEWL), the film is identified as occlusive. AppHcation of a layer of petrolatum to normal skin can reduce the TEWL, which is normally about 4—8 g/(m h), by as much as 50 to 75% for several hours. The evaporated water is to a large extent trapped under the occlusive layer hydrating or moisturizing the dead cells of the stratum corneum. The flexibiHty of isolated stratum corneum is dependent on the presence of water dry stratum corneum is britde and difficult to stretch or bend. Thus, any increase in the water content of skin is beHeved to improve the skin quaHty. 

Fig. 4.3 Epidermal nerve fiber illustrated in a 50-pm vertical skin section, immunostained with the panaxonal marker anti-protein gene product 9.5. Skin section showing epidermal nerve fiber density arrows) in the distal leg of a healthy adult (a) and reduced epidermal nerve fiber density and degenerating fibers arrows) in the distal leg of a HIV-associated sensory neuropathy patient (b) (scale bar, 50 pm). Courtesy of Drs Gigi Ebenezer and Justin McArthur, Johns Hopkins University, Baltimore, Maryland, USA...

Epidermal nerve fiber analysis by immunocytochemical techniques using the panaxonal marker protein gene product 9.5 (PGP 9.5) allows the study of epidermal innervation by small fiber C and A5 nerve fibers (McCarthy et al. 1995 Holland et al. 1997). Studies of skin biopsies of HIV infected patients with DSP or ATN showed reduction in the number of epidermal fibers in distal areas of the lower extremities with an inverse correlation between neuropathic pain intensity and epidermal nerve fiber density (Polydefkis et al. 2002) (Fig. 4.3). There were also fewer epidermal fibers in HIV seropositive patients without clinical evidence of neuropathy, suggesting that HIV infection may be associated with the loss of cutaneous innervation even before the onset of sensory symptomatology (McCarthy et al. 1995). 

We have already stressed the potential importance of lipid-rich membranes in the skin as potential targets for ROS-induced damage and ageing of human skin is morphologically identical to changes found by peroxidative processes (Serri et al., 1977). The involvement of AA metabolites in skin disease, and in particular psoriasis, has been the subject of much recent interest. Studies have included topical and intradermal administrations of AA metabolites, and assay of such products in clinical specimens. Results show that concentration of AA, 12-hydroxy-eicosatetraenoic acid (12-HETE), PG and leu-kotrienes are increased in psoriatic lesions (Hammarstrom etal., 1975 Camp etal., 1983 Brain etal., 1984 Duell et al., 1988) and also that full-thickness epidermis from normal and diseased skin has the enzymatic capacity to convert AA to some of the same metabolites (Hammarstrom etal., 1975, 1979 Camp etal., 1983 Brain etal., 1984 Ziboh et al., 1984 DueU et al., 1988). The biological effect of both 12-HETE and leukotrienes was confirmed by both topical application and intradermal injection, which caused epidermal inflammation and... 

Epidermal growth factor suppresses nitric oxide and hydrogen peroxide production by keratinocytes. Potential role for nitric oxide in the regulation of wound healing. J. Biol. Chem. 267, 21277-21280. 

Transdermal Administration. The development of the stratum corneum is complete at birth and is considered to have permeability similar to that of adults, except in preterm infants [81], Preterm neonates and infants have an underdeveloped epidermal barrier and are subject to excessive absorption of potentially toxic ingredients from topically applied products. 

The site of pheromone production in flies and cockroaches that utilize hydrocarbons is similar to that of the moths. Oenocyte cells produce the hydrocarbon pheromone which is transported by lipophorin in the hemolymph to epidermal cells throughout the body for release from the cuticular surface in general [20,21]. 

LOX-dependent superoxide production was also registered under ex vivo conditions [55]. It has been shown that the intravenous administration of lipopolysaccharide to rats stimulated superoxide production by alveolar and peritoneal macrophages. O Donnell and Azzi [56] proposed that a relatively high rate of superoxide production by cultured human fibroblasts in the presence of NADH was relevant to 15-LOX-catalyzed oxidation of unsaturated acids and was independent of NADPH oxidase, prostaglandin H synthase, xanthine oxidase, and cytochrome P-450 activation or mitochondrial respiration. LOX might also be involved in the superoxide production by epidermal growth factor-stimulated pheochromo-cytoma cells [57]. 

As a result of pathogenic T-cell production and activation, psoriatic epidermal cells proliferate at a rate sevenfold faster than normal epidermal cells. Epidermal proliferation is also elevated in apparently normal skin of psoriatic patients. 

Topical corticosteroids (Table 16-1) may halt synthesis and mitosis of DNA in epidermal cells and appear to inhibit phospholipase A, lowering the amounts of arachidonic acid, prostaglandins, and leukotrienes in the skin. These effects, coupled with local vasoconstriction, reduce erythema, pruritus, and scaling. As antipsoriatic agents, they are best used adjunc-tively with a product that specifically functions to normalize epidermal hyperproliferation. 

Examples of the early application of recombinant DNA technology in medicine are the development of recombinant human growth hormone human insulin human interferons, thought to have anticancer activity in addition to antiviral activity interleukins (regulatory proteins from lymphocytes that are believed to be important in the treatment of immunodeficiency diseases and cancer) tumor necrosis factor epidermal and bone marrow progenitor cell growth factors and the production of vaccines (Table 12.1). 

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