Keratinocytes and

The CaR regulates numerous biological processes, including the expression of various genes (e.g., PTH) the secretion of hormones (PTH and calcitonin), cytokines (MCP-1), and calcium (e.g., into breast milk) the activities of channels (potassium channels) and transporters (aquaporin-2) cellular shape, motility (of macrophages), and migration cellular adhesion (of hematopoietic stem cells) and cellular proliferation (of colonocytes), differentiation (of keratinocytes), and apoptosis (of H-500 ley dig cancer cells) [3]. 

Salicylic acid has a keratolytic effect, thus eliminating superficial pigmented keratinocytes and stimulating cells turnover. This superficial peeling allows TCA to act a low concentration to remove pigmented keratinocytes through papillary dermis (see Fig. 14.12). 

Propionibacterium acnes (P. acnes), an anaerobic organism, is also found in the normal flora of the skin. This bacteria proliferates in the mixture of sebum and keratinocytes and can result in an inflammatory response producing a closed comedo or whitehead. More severe acne lesions such as pustules, papules, and nodules can also form with inflammatory acne and result in significant scarring if treated inadequately (Fig. 62-2). 

Open comedo or "blackhead" a plugged follicle of sebum, keratinocytes, and bacteria that protrudes from the surface of the skin and appears black or brown in color. Although dark in color, blackheads do not indicate the presence of dirt, but rather an accumulation of melanin. 

Once T cells are activated, they migrate from lymph nodes and the bloodstream into skin and secrete various cytokines (e.g., interferon % interleukin 2 [IL-2]) that induce the pathologic changes of psoriasis. Local keratinocytes and neutrophils are induced to produce other cytokines, such as tumor necrosis factor-a (TNF-a), IL-8, and others. 

Rosenthal, D.S., et al., Mechanisms of JP-8 jet fuel cell toxicity B. Induction of necrosis in skin fibroblasts and keratinocytes and modulation of levels of Bcl-2 family members, Toxicol. Appl. Pharmacol., 171, 107, 2001. 

Shopsis, C. (1989). Validation study ocular irritancy prediction with the total cell protein, uridine uptake, and neutral red assays applied to human epidermal keratinocytes and mouse 3t3 cells. In Alternative Methods in Toxicology, Vol. 7 (Goldberg, A.M., Ed.). Mary Arm Liebert, New York, pp. 273-287. 

Karp, J.M., Rodrigo, K.A., Pei, P., Pavlick, M.D., Andersen, J.D., McTigue, D.J., Fields, H.W. and Mallery, S.R. (2005) Sanguinarine activates polycyclic aromatic hydrocarbon associated metabolic pathways in human oral keratinocytes and tissues. Toxicology Letters, 158, 50-60. 

With regard to surface molecule expression of keratinocytes and their role in immunoregulation, a recent study by Loser et al. [49] showed that the member of the TNF superfamily, RANKL, is expressed on keratinocytes of inflamed human and mouse skin. In a murine system, RANKL overexpression in keratinocytes resulted in functional alterations of epidermal dendritic cells and systemic... 

Particles from cationic lipids may also be useful for antisense therapy of skin disease — a nontoxic increase in the oligonucleotide uptake by cultivated keratinocytes and a sebocyte cell line has been reported [66]. Moreover, cationic dendri-mers also efficiently transfer reporter gene DNA to human keratinocytes cultivated in vitro. In the skin of hairless mice, in vivo transfection was possible with complexes, yet reporter gene expression was localized to perifollicular areas. Transfection, however, failed with the naked plasmid. For prolonged contact, biodegradable membranes coated with dendrimer/DNA complexes were used [67]. This hints at a follicular uptake of these complexes and indicates that gene transfection also may be possible with human skin, which has a thicker stratum comeum compared with mouse skin (eight to ten vs. two to three layers [58]). 

Possibilities of method of hybrid cultures obtaining which are used in biotechnology, for scientific and diagnostic researches are unlimited. The obtaining of hybrids with hepatocytes, enterocytes, keratinocytes and other cells, not growing or badly growing in vitro, is very perspective. 

Long-term use - Tretinoin is a dermal irritant, and the results of continued irritation of the skin for greater than 48 weeks are not known. There is evidence of atypical changes in melanocytes and keratinocytes and of increased dermal elastosis in some patients treated with tretinoin 0.05% for longer than 52 weeks. 

In the context of skin sensitization bioavailability can be seen as the capacity of the compound to reach the viable epidermis, where it interacts with keratinocytes and Langerhans cells. This capacity is dependent on its molecular weight and solubility in polar and apolar solvents [115]. Importantly, potency prediction solely on the basis of cell culture models (steps 3 and 4) does not account for skin penetration rate and may thus wrongly predict potency in vivo. Possible in vitro approaches to detect allergic capacity of chemicals/pharmaceuticals are presented in Table 18.5. 

Finally, use of more complex models is in progress. For example, Lee et al. [77] studied the phototoxic impact of chemicals on reconstructed skin models that were prepared from cultured keratinocytes and melanocytes on de-epidermized dermis. 

Reid, L., Clothier, R.H. and Khammo, N. (2001) Hydrogen peroxide induced stress in human keratinocytes and its effect on bithionol toxicity. Toxicology In Vitro An International Journal Published in Association with BIBRA, 15, 441—445. 

Calcipotriene (Dovonex), a synthetic vitamin D3 derivative, is indicated for the treatment of moderate plaque psoriasis. Its mechanism of action is unknown, although it competes for calcitriol receptors on keratinocytes and normalizes differentiation. It also has a variety of immunomodulatory effects in the skin. Although the drug can cause local irritation, the most serious toxicities are hypercalciuria and hypercalcemia, which are usually reversible. 

Results of our experiments suggest that (1) dermal substitute biomaterials may contribute to the improved wound re-epithehalisation when combined with cultured autologous keratinocytes and (2) porcine collagen paste is able to support splitthickness skin graft survival as well as autologous cultured keratinocyte proliferation. 

Incubation of benzoyl peroxide with keratinocytes and the spin trap 5.5-dimetln l-l-... 

Methyl methanesulfonate induced DNA single-strand breaks and alkali-labile sites in human lymphocytes in vitro. It induced unscheduled DNA synthesis in human epidermal keratinocytes and in oral epithelial and fibroblast cell cultures. Methyl methanesulfonate induced gene mutations in human lymphoblasts at the hprt locus and sister chromatid exchanges and micronuclei in HepG2 human liver cells in vitro. 

The dendrites of a melanocyte contact about 36 keratinocytes and are able to transfer melanosomes to these adjacent cells. The numbers and sizes of the melanosomes as well as melanin structure determine differences in skin color.131 Similar cells in amphibians, the melanophores, also contain light receptors p Their melanosomes are not transferred to other cells but may be either clustered near the center of the cell or dispersed. The location can be changed quickly by transport of the melanosomes along a network of microtubules allowing the animals to change in response to changes in light color.0)... 

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