Cornified

It is a lipophilic compound which removes intercellular lipids that are covalently linked to the cornified envelope surrounding epithelial cells [3]. It also enhances penetration of other agents. Resorcinol (m-dihydroxy benzene) is structurally and chemically similar to phenol. It disrupts the weak hydrogen bonds of keratin [4]. Lactic acid is an alpha hydroxy acid which causes corneocyte detachment and subsequent desquamation of the stratum corneum [5]. 

The earliest morphological change in the sebaceous follicle is an abnormal follicular epithelial differentiation, which results in ductal hypercornification. Cornified cells in the upper section of the follicular canal become abnormally adherent. Comedones represent the retention of hyperproliferating ductal keratinoc-ytes in the duct. Several factors have been implicated in the induction of hyperproliferation sebaceous lipid composition, androgens, local cytokine production (IL-i, EGF) and bacteria (P. acnes). 

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. 

Stratum Comeum The cornified skin layers may be isolated by digestion of the connective epidermal tissue using trypsin in buffer solutions of pH 7.4. 

Assessing the depth by determining the protein amount removed per strip, Mueller et al. noted a nonlinear steady-state concentration gradient which they ascribed to an increased permeability of the cornified envelope within the... 

Kasturi L, Sizemore N, Eckert RL, Martin K, and Rorke EA [1993] Calcium modulates cornified envelope formation, involucrin content, and transglutaminase activity in cultured human ectocervical epithelial cells. Exp Cell Res 205 84-90... 

Salicylic acid is a keratolytic agent that removes layers of cornified skin cells. Treatment for corns, calluses and warts involves the application of salicylic acid at a concentration of 1 1-50%. Salicylic acid is contraindicated in allergic patients and its use should be avoided in diabetic patients. 

The animals treated with 200, 400, and 800 lU A showed a healing effect of vitamin A on the cornified vaginal epithelium as early as 2 days after starting the experiment. In the smear of all concentrations, almost exclusively leukocytes — indicating a successful healing and mucosal regeneration — with only sporadic epithelial cells and squamous cells... 

Mecfianism of Action A wart removal agent that produces desquamation of hyper-keratotic epithelium by dissolution of intercellular cement and causes the cornified tissue to swell, soften, macerate, and desquamate. Therapeutic Effect Decreases acne, psoriasis and promotes wart removal... 

Steinert, P. M., and Marekov, L. N. (1997). Direct evidence that involucrin is a major early isopeptide crosslinked component of the keratinocyte cornified cell envelope./ Biol. Chem. 272, 2021-2030. 

Aho, S., Li, K., Ryoo, Y., McGee, C., Ishida-Yamamoto, A., Uitto,J., and Klement, J. F. (2004). Periplakin gene targeting reveals a constituent of the cornified cell envelope dispensable for normal mouse development. Mol. Cell. Biol. 24, 6410-6418. 

Lee, S.-C., Kim, I.-G., Marekov, L. N., O Keefe, E. J., Parry, D. A. D., and Steinert, P. M. (1993). The structure of human trichohyalin Potential multiple roles as a functional EF-hand-like calcium-binding protein, a cornified cell envelope precursor, and an intermediate filament-associated (cross-linking) protein. / Biol. Chem. 268, 12164-12176. 

Maatta, A., DiColandrea, T., Groot, K., and Watt, F. M. (2001). Gene targeting of envoplakin, a cytoskeletal linker protein and precursor of the epidermal cornified envelope. Mol. Cell. Biol. 21, 7047-7053. 

Simon, M., Haftek, M., Sebbag, M., Montezin, M., Girbal-Neuhauser, E., Schmitt, D., and Serre, G. (1996). Evidence that filaggrin is a component of cornified cell envelopes in human plantar epidermis. Biochem. J. 317, 173-177. 

The outermost layer of the skin, the cornified layer or stratum corneum, has been identified as the principal diffusion barrier for substances, including water [2,3]. It is approximately 10 to 20 pm thick when dry but swells to several times this thickness when fully hydrated [17], It contains 10 to 25 layers lying parallel to the skin surface of nonviable cells, the corneocytes, which are surrounded by a cell envelope and imbedded in a lipid matrix. This architecture is often modeled as a wall-like structure, with the corneocytes as protein bricks embedded in a lipid mortar [18]. Similarly to the viable epidermis, desmosomes (corneodesmosomes) contribute to the cell cohesion. 

Compounds that penetrate the stratum corneum via the transepidermal route may follow a transcellular (or intracellular) or intercellular pathway (see Figure 11.1). Because of the highly impermeable character of the cornified envelope (see previous section), the tortuous intercellular pathway has been suggested to be the route of preference for most drug molecules [32], This is confirmed by several microscopic transport studies, in which compounds have been visualized in the intercellular space of the stratum corneum [33-35]. Moreover, it has been demonstrated that drug permeation across stratum corneum increases many folds after lipid extraction [36], Hence, knowledge of the structure and physical properties of the intercellular lipids is crucial to broaden our insight into the skin barrier function. 

Hirao, T. 2003. Involvement of transglutaminase in ex vivo maturation of cornified envelopes in the stratum corneum. Ini J Cosmet Sci 25 245. 

Hohl, D., M. Huber, and E. Frenk. 1993. Analysis of the cornified cell envelope in lamellar... 

Figure 26.3 Percent of total days with estrous cytology in SD female rats fed atrazine in the diet. (Vaginal cytology was monitored daily for 14-day intervals, followed by 14 days of rest. Estrous cytology was defined by the presence of a majority of keratinized (cornified) cells in the lavage. Each point represents the mean S.E. of 60 animals per dose group. The mean responses to 400ppm at 13-14, 17-18, 21-22, and 25-26 weeks were significantly different from controls (ANOVA, p <. 05) other mean values were not significantly different.)...

FIGURE 4.3 High magnification transmission electron micrographs of multilamellar membrane structures in the intercellular space of the cornified part of human epidermis. (A) cryo-electron micrograph of vitreous section. (B, C) conventional electron micrographs of resin embedded sections. The cell plasma membranes appear as 3.8 nm wide bilayers in (A) (open white arrow). A 16 nm broad zone of electron dense material, the cornified cell envelope (white asterix), is directly apposed to the cytoplasmic side of the bilayer plasma membranes in the native sample (A) (open white arrow). Scale bar 50 nm (A). Scale bars 25 nm (B, C) adapted from measures given in Swartzendruber et al. (1989). (A) reprinted from Norlen (2003). With permission from Blackwell Science Publications. (B, C) reprinted from Swartzendruber et al. (1989). With permission from Blackwell Science Publications. 

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