Epithelia nasal epithelium

Site-of-contact tissues might be preferable for such compounds (Burlinson 1989 Furihata et al. 1984 Furihata and Matsushima 1987 Mori et al. 1999 Sawyer et al. 1988), if sufficiently validated. The main technical limitation of this assay with respect to other tissues is the need to isolate the cells after in vivo treatment and to get them to incorporate tritiated thymidine in vitro. Because UDS measurement does not require cell division, it can potentially be applied to many different tissues, provided that the cells can be isolated and maintained in primary culture for the few hours required for tritiated thymidine incorporation. The literature contains reports of UDS-based studies of stomach, colon, kidney, pancreas, tracheal epithelium, nasal epithelium, epidermis, keratinocytes, and spermatocytes (Burlinson 1989 Furihata et al. 1984 Furihata and Matsushima 1987 Sawyer et al. 1988 Loury et al. 1987 Mori et al. 1999 Latt et al. 1981 Helleday 2003). 

Wilson D.B. and Hendrickx A.G. (1977). Quantitative aspects of proliferation in the nasal epithelium of the rhesus monkey embryo. J Emb Exp Morphol 38, 217-226. 

Although the ocular absorption of peptide as well as nonpeptide drugs is poor [96,196-198], the ocular route is by far the least studied for the usefulness of penetration enhancers. This is in part due to the perceived sensitivity of ocular tissues to irritation and the fear of corneal and conjunctival damage caused by the enhancers. Whereas the rat nasal epithelium may tolerate up to 5% sodium glycocholate [199], ocular administration of sodium glycocholate at a concentration of 2% and beyond induces reddening of the eye and tear production in rabbits (Kompella and Lee, unpublished observation). 

Morimoto et al. [33] demonstrated that the ocular absorption of hydrophilic compounds over a wide range of molecular weights could be increased by 2 and 10 mM sodium taurocholate and sodium taurodeoxycholate in a dose-dependent manner. The compounds were glutathione (307 Da), 6-carboxyfluorescein (376 Da), FTTC-dextran (4 kDa), and insulin (5.7 kDa). Of the two bile salts, sodium taurodeoxycholate was more effective. At 10 mM, this bile salt increased the permeability of 6-carboxyfluorescein from 0.02% to 11%, glutathione from 0.08% to 6%, FITC-dextran from 0% to 0.07%, and insulin from 0.06% to 3.8%. Sodium taurocholate, on the other hand, increased the permeability to 0.13%, 0.38%, 0.0011%, and 0.14%, respectively. Taurodeoxycholate was more effective than taurocholate in the nasal epithelium as well [202], This difference in activities can possibly be attributed to their micelle-forming capability, which is higher for taurodeoxycholate, a dihydroxy bile salt [190],... 

Radon daughters are deposited on the surface of mucus lining the bronchi. It is generally assumed that the daughter nuclides, i.e. polonium-218 (RaA), lead-214 (RaB) and bismuth-214 (RaC), remain in the mucus and are transported towards the head. However, one dosimetric model assumes that unattached radon daughters are rapidly absorbed into the blood (Jacobi and Eisfeld, 1980). This has the effect of reducing dose by about a factor of two. Experiments in which lead-212 was instilled as free ions onto nasal epithelium in rats have shown that only a minor fraction is absorbed rapidly into the blood (Greenhalgh et al., 1982). Most of the lead remained in the mucus but about 30% was not cleared in mucus and probably transferred to the epithelium. 

Caplen NJ, Alton EW, Middleton PG, Dorin JR, Stevenson BJ, Gao X, Durham SR, Jeffery PK, Hodson ME, Coutelle C (1995) Liposome-mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis. Nat Med 1 39-46... 

Ziady AG, Kelley TJ, Milliken E, Ferkol T, Davis PB (2002) Functional evidence of CFTR gene transfer in nasal epithelium of cystic fibrosis mice in vivo following luminal application of DNA complexes targeted to the serpin-enzyme complex receptor. Mol Ther 5 413-419... 

HCN is detoxified to thiocyanate (SCN ) by the mitochondrial enzyme rhodanese rhodanese catalyzes the transfer of sulfur from thiosulfate to cyanide to yield thiocyanate, which is relatively nontoxic (Smith 1996). The rate of detoxification of HCN in humans is about 1 pg/kg/min (Schulz 1984) or 4.2 mg/h, which, the author states, is considerably slower than in small rodents. This information resulted from reports of the therapeutic use of sodium nitroprusside to control hypertension. Rhodanese is present in the liver and skeletal muscle of mammalian species as well as in the nasal epithelium. The mitochondria of the nasal and olfactory mucosa of the rat contain nearly seven times as much rhodanese as the liver (Dahl 1989). The enzyme rhodanese is present to a large excess in the human body relative to its substrates (Schulz 1984). This enzyme demonstrates zero-order kinetics, and the limiting factor in the detoxification of HCN is thiosulphate. However, other sulfur-containing substrates, such as cystine and cysteine, can also serve as sulfur donors. Other enzymes, such as 3-mercapto-pyruvate sulfur transferase, can convert... 

The extent of drug absorption following nasal administration depends to a reasonable extent on the ease with which a drug molecule crosses the nasal epithelium without degradation or rapid clearance by the mucociliary clearance system. The effects of these two elimination components are more pronounced for proteins and peptides. The nasal administration of drugs, especially proteins and peptides, as well as other molecules has been studied with excised tissues harvested from rabbit, cow, sheep, and pig species (Table 5.2). A... 

Cremaschi et al. [39] investigated transepithelial pathways of eel calcitonin, corticotrophin, sucrose, and polyethylene glycol-4000 (PEG-4000) transport across the nasal epithelium using rabbit nasal mucosa mounted on Ussing chamber that was maintained at 27°C. The electrical parameters of the tissues were those of leaky epithelium that allow macromolecules to permeate paracellularly their observation was similar to the finding made by McMartin et al. [40] in which the authors described the nasal epithelium as leaky with... 

Ohtake K, Maeno T, Ueda H, Ogihara M, Natsume H, Morimoto Y (2003) Poly-L-arginine enhances paracellular permeability via serine/threonine phosphorylation of ZO-1 and tyrosine dephosphorylation of occludin in rabbit nasal epithelium. Pharm Res 20 1838-1845. 

Agu RU, Vu Dang H, Jorissen M, Willems T, Kinget R, Verbeke N (2002) Nasal absorption enhancement strategies for therapeutic peptides an in vitro study using cultured human nasal epithelium. Int J Pharm 237 179-191. 

Merkus FWHM, Marttin E, Romeijn SG, Verhoef J (1996) In situ perfusion is an unrealistic approach to assess the effects of absorption enhancers on nasal epithelium. Eur J Pharm Biopharm 42 159. 

Schmidt MC, Simmen D, Hilbe M, Boderke P, Ditzinger G, Sandow J, Lang S, Rubas W, Merkle HP (2000) Validation of excised bovine nasal mucosa as in vitro model to study drug transport and metabolic pathways in nasal epithelium. J Pharm Sci 89 396-407. 

Harkema JR, Carey SA, Wagner (2006) The nose revisited a brief review of the comparative structure, function, and toxicologic pathology of the nasal epithelium. Toxicol Pathol 34 252-269. 

In vitro cell culture models of human nasal epithelium based on primary culture technologies have proven to be extremely useful for mechanistic studies of nasal epithelial permeability and drug absorption [13]. However, efforts... 

This refers to the transport across the epithelial cells, which can occur by passive diffusion, carrier-mediated transport, and/or endocytic processes (e.g., transcytosis). Traditionally, the transcellular route of nasal mucosa has been simply viewed as primarily crossing the lipoidal barrier, in which the absorption of a drug is determined by the magnitude of its partition coefficient and molecular size. However, several investigators have reported the lack of linear correlation between penetrant lipophilicity and permeability [9], which implies that cell membranes of nasal epithelium cannot be regarded as a simple lipoidal barrier. Recently, compounds whose transport could not be fully explained by passive simple diffusion have been investigated to test if they could be utilized as specific substrates for various transporters which have been identified in the... 

Since the uptake of particles in nasal epithelial tissue is known to be mostly mediated by M cells, nasal administration has been investigated as a noninva-sive delivery of vaccines [37], However, since the uptake of naked DNA by endocytocis is limited, use of either nanoparticles as mucosal delivery systems [37] or hypotonic shock [38] is reported for the efficient transfection of gene and vaccine into the nasal epithelium. It was also reported that polypeptides and polypeptide-coated nanospheres (diameter about 500 nm) are transported through endocytic process in rat M cells [39],... 

R. Agu, H. V. Dang, M. Jorissen, T. Willems, S. Vandoninck, J. Van Lint, J. V. Vandenheede, R. Kinqet, and N. Verbeke. In vitro polarized transport of L-phenylalanine in human nasal epithelium and partial characterization of the amino acid transporters involved. Pharm Res 20 1125-1132 (2003). 

U. Werner and T. Kissel. In-vitro cell culture models of the nasal epithelium A comparative histochemical investigation of their suitability for drug transport studies. Pharm Res 13 978-988 (1996). 

C. Ruckes, U. Blank, K. Moller, J. Rieboldt, H. Lindemann, G. Munker, W. Clauss, and W. M. Weber. Amiloride-sensitive Na+ channels in human nasal epithelium are different from classical epithelial Na+ channels. Biochem Biophys Res Commun 237 488-491 (1997). 

T. Kissel and U. Werner. Nasal delivery of peptides An in vitro cell culture model for the investigation of transport and metabolism in human nasal epithelium. J Control Release 53 195-203 (1998). 

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