Lipid Barrier

Law S, Wertz PW, Swartzendruber DC, Squier CA (1995) Regional variation in content, composition and organization of porcine epithelial barrier lipids revealed by thin-layer chromatography and transmission electron microscopy. Arch Oral Biol 40 1085-1091... 

Alkali is a frequent cause of eye bums as again confirmed in a recent study of Midelfarth [22], Alkali reacts with the tissue surface by concentration and time-dependent dissolution of the Upid membranes of epithelial cells the chemical mechanism is saponification of lipids with loss of all membranous barriers. Lipid saponification of membranous lipids starts at a pH over 11 [23]. 

STRATUM CORNEUM BARRIER LIPIDS 11.3.1 Penetration Pathway through the Stratum Corneum... 

Looking at the barrier in more detail, we find that it can be described as composed of two main components. Interspersed between the corneocytes we find the hydrophobic (water-repellent) substance, the barrier lipids. The keratinized corneocytes containing fibrous and amorphous proteins represent a hydrophilic (water-attracting) component. Neutral lipids (fatty acids, cholesterol) and ceramides dominate the lipid phase, and it is mainly these lipids that are responsible for the control and limitation of water transport through the skin.14 Visualization of the penetration pathway through the skin by tracer methods has demonstrated that the extracellular pathway is likely to be the only route through the barrier for substances other than water.15 Water diffusion through the keratinocytes... 

As a generalization, we may be allowed to state that the transition temperature for cell membranes in biological living systems is found between 0 and 40°C and the chain lengths are between 16 and 18 carbons. This is in conspicuous contrast to the lipids of the stratum corneum barrier where chain lengths up to and over 30 carbons have been demonstrated.14,19 From such facts we expect the transition temperature of the skin barrier lipids to be around 40°C, and this has also been substantiated in a number of investigations.20-22 This means that under normal conditions with a skin temperature about 30°C, the barrier will essentially be impermeable to water. 

The recent data of Norlen et al.16,28 demonstrate that the FFA retrieved from stripped lower arm skin (and therefore essentially uncontaminated by sebum lipids) are all saturated and long-chain species (C > 20). This harmonizes with lipid data from epidermal cysts, which are virtually free from triglycerides of sebum origin.29 Furthermore, the ceramides of the barrier lipids are all long-chain species and therefore also comply with the requirement set up for a water-impermeable barrier. 

The lipid bilayers of the stratum corneum not only constitute a barrier, but may also function as a pool from which substances can slowly penetrate into the system on a downhill gradient. The actual effect of solvents and detergents on barrier lipid structure is not known in any satisfactory detail. Likewise, we are only starting to understand how different moisturizers might influence the structure and function of the barrier. We still lack an understanding of how the composition of the ceramide, FFA, and cholesterol influences the defect barrier in some pathological disorders, for example, dry atopic skin. 

The unique character and the particular composition of the human skin barrier lipids call for investigations on human skin, possibly pig skin, and to a great extent preclude rodents as models for barrier function in penetration studies. 

Ponec, M., Weerheim, A., Kempenaar, J., Mulder, A., Gooris, G.S., Bouwstra, J., and Mommaas, A.M., The formation of competent barrier lipids in reconstructed human epidermis requires the presence of vitamin C, J. Invest. Dermatol., 109, 348, 1997. 

Enzyme diffuses towards corneodesmosomes to begin their degradation and encapsulation with barrier lipids, transformation of fragile to resilient corneocyte... 

The transformation of the fluid- to gel-state lipids is achieved by the catabolism of the pro-barrier lipids and the subsequent synthesis of the barrier lipids. In stratum basale, up to 60% of the lipids... 

The EFA metabolism is presented in several extensive reviews.9 16 17 Much of the information concerning EFA physiology and biochemistry has been derived from work in hepatocytes and may be of limited relevance to epidermis since a major role of the liver is to convert dietary lipids into energy stores. Meanwhile, keratinocytes are involved in the fatty acid metabolism required both for normal cellular processes and the specialized role in the permeability barrier. Unlike the liver, the epidermis does not possess the capacity to desaturate at the A5 or A6 position, and therefore the skin relies on a supply of AA, LA, and ALA from the bloodstream. There is evidence for a distinct fatty acid binding protein in keratinocyte plasma membranes that is involved in EFA uptake into the skin and also recycling of free fatty acids from the stratum corneum.18 The transport mechanism in epidermis differs from that in hepatocytes since there is preferential uptake of LA over OA, which may function to ensure adequate capture of LA for barrier lipid synthesis.18... 

De Paepe, K., Roseeuw, D., and Rogiers, V., Repair of acetone- and sodium lauryl sulphate-damaged human skin barrier function using topically applied emulsions containing barrier lipids, J. Eur. Acad. Dermatol. Venereol., 16, 587, 2002. 

New folate antagonists have been identified that are better substrates for the reduced folate carrier and appear to have significant advantages in clinical chemotherapy (see pemetrexed below). In efforts to bypass the obligatory membrane transport system and to facilitate penetration of the blood—brain barrier, lipid-soluble folate antagonists also have been synthesized. Trime-trexate (NEVTREXIN) has modest antitumor activity, primarily in combination with leucovorin rescue. However, it is beneficial in the treatment Pneumocystis jiroveci pneumonia, where leucovorin provides differential rescue of the host but not the parasite. 

The suggestion has been made that hepoxil-ins are more relevant lipids regarding this disease [1648]. The hepoxilins (or trioxilins) ntight be oxidized and play a role in signaling, rather than acting directly as barrier lipids [1643]. 

Our work has been based on the knowledge of the unique composition of the barrier lipids of the naked ape compared with that of furry animals or genetically manipulated naked-animal species (Forslind i994> 1995 Forslind et al. 1997). Chromatographic analyses of the lipids extracted from human and mammal skins have revealed that human skin is... 

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