Epidermal barrier

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. 

Colorimetric, spectrophotometric and histochemical studies have shown that the homy layer is the epidermal barrier to nickel absorption [270]. The carboxyl groups of the keratin have been found to be important in the binding of nickel [271, 272],... 

There are several genetic skin diseases with known defects in the lipid metabolism. Atopic dermatitis, lamellar ichthyosis, and psoriasis have been the most widely studied with respect to epidermal barrier function and alterations in the lipid profile. Deviations in the lipid profile have been linked with an impaired stratum corneum barrier function. Atopic dermatitis is characterized by inflammatory, dry and easily irritable skin, and overall reduced ceramide levels in the stratum corneum [58-60]. In particular a significant decrease in the ceramide 1 level is observed, whereas the levels of oleate that is esterified to ceramide 1 are elevated [59]. Both aberrations may be responsible for the reduced order of the lamellar phases as observed with freeze fracture electron microscopy [61]. It has further been established that, in comparison to healthy stratum corneum, the fraction of lipids forming a hexagonal packing is increased [61]. A recent study reveals that the level of free fatty acids... 

Fartasch, M. 1997. Epidermal barrier in disorders of the skin. Microsc Res Tech 38 361. 

Tupker, R.A., J. Pinnagoda, and J.P. Nater. 1990. The transient and cumulative effect of sodium lauryl sulphate on the epidermal barrier assessed by transepidermal water loss Inter-individual variation. Acta Derm Venereol (Stockh) 70 1. 

Palmer, C. N., Irvine, A. D., Terron-Kwiatkowski, A., Zhao, Y., Liao, H., Lee, S. P., et al. (2006) Common loss-of-fiinction variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nat Genet 38, 441-446. 

Furuse, M., Hata, M., Furuse, K., Yoshida, Y., Haratake, A., Sugitani, Y., Noda, T., Kubo, A., and Tsukita, S. (2002) Claudin-based tight-junctions are crucial for the mamallian epidermal barrier a lesson from claudin-1-deficient mice. J. Cell Biol. 156(6) 1099-1111. 

The treatment of EHK is complicated. On the one hand, hyperkeratosis must be reduced to minimize the disfiguring and foul-smelling scales. On the other hand, skin blisters and erosions must be protected from irritation in order to heal. A too potent keratolytic treatment will often aggravate the condition by disrupting the epidermal barrier and increasing the risk for painful and... 

Nickoloff, B.J. and Naidu, Y. (1994) Perturbation of epidermal barrier function correlates with initiation of cytokine cascade in human skin. J. Am. Acad. Dermatol. 30 535-546. 

Fartasch, M. (1997) Ultrastructure of the epidermal barrier after irritation. Microsc. Res. Tech. 37 193-199. 

Holleran, W.M., Uchida, Y., Halkier-Sorensen, L., Haratake, A., Hara, M., Epstein, J.H., and Elias, P.M., Structural and biochemical basis for the UVB-induced alterations in epidermal barrier function, Photodermatol, Photoimmunol. Photomed., 13, 117-128, 1997. 

The G-protein coupled receptors modulate intracellular cAMP level, which plays a crucial role in epidermal barrier homeostasis.5 Increase of intracellular cAMP in epidermal keratinocytes by topical application of forskolin delays barrier recovery, while cAMP antagonists accelerate the barrier recovery. Activation of dopamine 2-like receptors (manuscript in preparation), melatonin receptors, or serotonin receptor (type 5-HT1) decreases intracellular cAMP and consequently accelerates the barrier recovery (Figure 15.1), while activation of adrenergic 32 receptors increases intracellular cAMP and delays the barrier repair.6 Barrier disruption induces an increase of the intracellular cAMP level. Thus, topical application of agonists of receptors that reduce intracellular cAMP accelerates the barrier repair. Our results are summarized in Table. 15.1. 

Taieb, A., Hypothesis from epidermal barrier dysfunction to atopic disorders, Contact Derm., 41,177, 1999. 

The mode of action of glycerol both on SC hydration and epidermal barrier function seems to be related to the aquaporin-3 (AQP3) channel. The basal layer of epidermal keratinocytes contains AQP3, a small membrane protein that functions as a facilitated transporter of water and glycerol.11 Glycerol is transported very slowly into the epidermis and thus its transport rate is sensitive to the intrinsic glycerol permeability of the basal keratinocyte layer. 

In addition to the repair of the epidermal barrier, petrolatum has been used in other types of dermatological treatments. Petrolatum can affect the transmission of UV light during phototherapy... 

Lysophosphatidylcholine protects mice in the lipopolysacharide-induced septic shock.11 The fact that the lipopolysacharide increases the concentration of cytokines (the same effect is observed upon the epidermal barrier disruption), and that lysophosphatidylcholine normalizes the cytokines level, provides the theoretical basis for treating disorders of the skin. 

In addition to restoring the clinical appearance of xerotic skin, lanolin can also accelerate the restoration of normal barrier function to normal skin that has been acutely perturbed. Elias and colleagues have demonstrated that lanolin accelerated epidermal barrier recovery following perturbation with acetone.41 Three percent lanolin not only significantly (p < 0.001) decreased the TEWL at 45 min, but also after 4 h compared to vehicle-treated sites (Table 25.1). However, the rate of barrier recovery of lanolin-treated sites between 45 min and 4 h was not significantly different compared to vehicle treatment. This indicates that lanolin has an immediate effect on restoring a permeability barrier and does not interfere with the process of lamellar body extrusion and lipid synthesis, which are required for continued recovery. The effect of 3% lanolin on barrier recovery was very similar to that of the optimized ratio of stratum corneum lipids (ceramides, cholesterol, and fatty acids).42,43... 

Fartasch, M., Teal, J., and Menon, G.K., Mode of action of glycolic acid on human stratum corneum ultrastructural and functional evaluation of the epidermal barrier, Arch. Dermatol. Res., 289, 404, 1997. 

Gehring, W. and Gloor, M., Effect of topically applied dexpanthenol on epidermal barrier function and stratum corneum hydration. Results of a human in vivo study, Arzneimittelforschung, 50, 659, 2000. 

Chapter 15 New Methodology to Improve Epidermal Barrier Homeostasis 155 Mitsuhiro Denda... 

Skin diseases including essential fatty acid deficiency and ichthyosis may also affect the transdermal delivery of a compound. Studies have shown that the epidermal barrier function is altered by abnormal lipid composition in noneczematous atopic dry skin. Numerous other dermatologic conditions affect the anatomical structure and function of skin, which may impact on the nature of the toxic responses seen. 

The main sources of TNFa in the skin are mast cells, resident keratinocytes and Langerhans cells. Mature mast cells contain significant quantities of preformed TNFa in their granules that are released in an IgE-dependent manner. Investigators studying the inflammatory response in mouse skin revealed by Western blot analysis that exposure to acetone and tape stripping increased TNFa expression by 72% at 2.5 hr after treatment. The mRNA levels were highest at 1 hr after acetone, and then they decreased to control levels by 8 hr. These studies indicate an immediate response of TNFa to irritants that perturb the epidermal barrier. 

Monteiro-Riviere, N. A., Inman, A. O., Mak, V., Wertz, P., and Riviere, J. E. Effect of selective lipid extraction from different body regions on epidermal barrier function. Pharm. Res. 

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