Chemical Damage

When the stratum corneum is perturbed, several localized biochemical events occur that result in rapid reconstitution of barrier function (64,129-137). Thus, in extreme cases of stratum corneum damage, such as acetone-induced delipidation (129-131) or tape-stripping (137), there appears to be a biphasic pattern of recovery: a rapid phase of repair, followed by a slower phase of normalization. The initial rapid phase of barrier recovery involves the expeditious secretion of preformed lamellar bodies from the granular cells into the intercellular space (64), an increase in epidermal cholesterol and fatty acid synthesis (134,135), and accelerated production and secretion, into the intercellular space, of new lamellar bodies. The subsequent and slower phase of barrier repair involves an increase in ceramide synthesis (135) and an increase in DNA synthesis (136) leading to epidermal hyperplasia. A similar response to barrier perturbation occurs following treatment of the skin with sodium dodecyl sulfate (SDS) (137), but the magnitude of the response depends on the severity of

Figure 11 During hydration the lacunae formed by degrading desmosomes provide an obvious site for water pooling and, during prolonged exposure to water, lateral expansion of the lacunae occurs through polar-head regions of the intercellular lipids. Although the expansion of the individual lacunae may lead to a continuous lacunar system, this process does not appear to disrupt the lipid lamellae. Menon and Elias (127) have proposed that the continuous lacunal system may represent a putative aqueous "pore" pathway through the stratum corneum.

Figure 11 During hydration the lacunae formed by degrading desmosomes provide an obvious site for water pooling and, during prolonged exposure to water, lateral expansion of the lacunae occurs through polar-head regions of the intercellular lipids. Although the expansion of the individual lacunae may lead to a continuous lacunar system, this process does not appear to disrupt the lipid lamellae. Menon and Elias (127) have proposed that the continuous lacunal system may represent a putative aqueous "pore" pathway through the stratum corneum.

the induced perturbation. It is remarkable that the initial perturbation, which occurs in the outermost layers of the stratum corneum, can rapidly stimulate biochemical events in the stratum granulosum and lower levels of the epidermis.

Although the exact mechanisms stimulating these events are unknown, there is some indication that a change in the rate of transepidermal water loss (TEWL) induced by barrier alterations, may play a role (131). This increase in TEWL may lead to focal changes in the concentration of certain ions in the outer epidermis. In the normal state, the epidermis possesses a Ca2+ ion gradient such that there is more Ca2+ in the outer layers than the inner (138). Following barrier disruption the Ca2+ gradient is lost. The presence of higher levels of intracellular Ca2+ in the outer epidermis is believed to block lamellar body secretion (139,140), and reduced levels will stimulate secretion. In addition, K+ may play a role in this homeostatic mechanism and may also influence barrier repair independently of Ca2+ (141). Thus, although there are still many uncertainties concerning the biochemistry of barrier repair, there is much evidence that suggests the role of ion concentration and the induction of lipid-producing enzymes; such as 3-hydroxy-3-methylglutaryl coenzyme A and serine palmitoyl transferase (142).

Perturbation of barrier function sometimes, but not always, also induces an inflammatory response that results in irritation. It is important to appreciate that irritation is used to describe skin reactions that can range from a mild and transient erythema or itch, to serious vesiculation (see Chaps. 12 and 13). Whereas the insults of solvent delipidation and tape-stripping of the stratum corneum result in barrier repair and epidermal hyperplasia, they do not necessarily lead to an irritant reaction. On the other hand, application of SDS almost always results in an irritant response (143,144). Although solvent delipidation and tape-stripping of the stratum corneum both physically remove the intercellular lipid lamellae, which results in considerable increases in TEWL, SDS intercalates with the lamellae and increases fluidity in this region (145), resulting in an increase in TEWL. Furthermore, although other surface-active agents, such as sodium laurate and polysorbates, can increase TEWL to levels similar to SDS, the resultant irritation is much less and, in some cases, not significantly different from untreated skin (146). It follows that irritation subsequent to exposure to SDS must be a result of factors other than an increase in water transport and the stimulation of lipogenesis.

That surface-active agents can cause skin irritation is well established and has been so for many years (147). Also, whereas ionic surfactants can cause severe irritation, nonionic surfactants are considered virtually nonirritant in normal use (148,149). Thus, much of the research on surfactant-induced skin irritation has involved studies on SDS. The collective data suggest that SDS can interact with both lipid and protein structures in the stratum corneum. Interaction with lipids will increase lipid fluidity and thereby enhance skin permeability. This alone, however, apart from increasing its own permeation, will not account for the irritation caused by SDS. Although SDS can penetrate into the corneocyte and interact with the protein structure such that a-keratin is uncoiled (150), it is difficult to relate this aspect to an irritant response. A more likely explanation for the irritation induced by SDS is its capacity to stimulate keratinocyte production of inflammatory mediators such as IL-1 and PGE2 (151). Whether this induction is secondary to some interaction between SDS and the corneocyte cell membrane is unknown.

There is a range of mechanisms by which solvents may affect skin permeability, as proposed by Menon et al. (152). Suhonen et al. (89) recently reviewed chemical enhancement in terms of stratum corneum alterations. They suggested that both hydration and temperature effects by transitions were involving the hydrocarbon chains of the stratum corneum lipid components. They suggested that enhancer actions could be located either in the lipid region near the polar head group or between the hy-drophobic tails. Extraction of lipids would also lead to an increase in disorder because there is more space (free volume) in which the hydrocarbon chains can move (Fig. 12). Suhonen et al. (89) suggest that ethanol may act by displacing bound water molecules at the lipid headgroup-membrane interface region with a resulting increased interdigitation of the hydrocarbon chains. Ethanol extracts lipids from the stratum corneum only at high concentrations, with a resulting greater free volume for the lipid chains, as shown by infrared spectroscopy.

Keratolytics are becoming increasing used to promote permeability of the human epidermis, especially the nail plate, to topical agents. Walters et al. (153) have previously reported that agents that act as accelerants on the epidermis may not necessarily do so with the nail plate. Many enhancers have an effect on intercellular lipids, which constitute less than 1% of the nail weight. Quintanar-Guerrero et al. (154) suggest that keratolytic agents may facilitate antimycotic penetration through the nail plate by pore formation. This effect, observed using scanning electron microscopy, was most pronounced for papain, followed by salicylic acid, and then urea. Effects on deeper regions of the nail required a combination of papain and salicylic acid. In general, keratolytics have a limited effect on skin permeability, emphasizing the role of the intercellular lipids as a barrier to skin penetration by solutes. It has been suggested that other agents that affect stratum corneum protein structures (e.g., propylene glycol, ethanol, and dimethyl sulfoxide), create a reversible conformation change in the keratin protein from an a-helix to a ^-sheet as a consequence of a replacement of water that is bound to polar protein side chains. Dithiothreitol, a disulfide-reducing agent, has also been suggested to enhance hydrophilic solute penetration by an altered protein conformation to the ^-sheet as a consequence of the appearance of free thiols.

How To Deal With Rosacea and Eczema

How To Deal With Rosacea and Eczema

Rosacea and Eczema are two skin conditions that are fairly commonly found throughout the world. Each of them is characterized by different features, and can be both discomfiting as well as result in undesirable appearance features. In a nutshell, theyre problems that many would want to deal with.

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