Barrier Integrity

The GI surface is lined by a single layer of epithelial cells. This cellular barrier coupled with the mucus layer provides 

There are, of course, many other in vitro, ex vivo, and in vivo endpoints that can be employed depending on target cell type, understanding of potential for GI effects related to the primary pharmacology of the target or lesions identified from preclinical models, such as fecal microflora composition, charcoal transit time, ileum contraction, or quantification of short-circuit current with Ussing chambers. For excellent review of endpoints for assessment of GI toxicity, the reader is referred to Kapp (2008). 

Aamann, L., Vestergaard, E.M., and Gr0nbaek, H. 2014. Trefoil factors in inflammatory bowel disease. World J Gastroenterol, 20(12) 3223-3230. 

Ayehounie, S., Stevens, Z., Landry, T., Cataldo, A., Armento, A., Klausner, M., and Hayden, P. 2014. Organotypic human small intestine tissue to assess epithelial restitution. 17th Annual AAPS NERDG Meeting, May 2014, Farmington, CT. 

Bastian, S.E.P., Walton, P.E., Ballard, F.J., and Belford, D.A. 1999. Transport of IGF-1 across epithelial cell monolayers. J Endocrinol, 162 361-369. 

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Guy, J., Ellis, E., Hope, G. and Rao, N.A. (1989b). Antioxidant enzymes reduce loss of blood-brain barrier integrity m experimental optic neuritis. Arch. Ophthalmol. 107, 1359-1363. 

As mentioned above, a subgroup of patients with atopic dermatitis has a filaggrin loss-of-function mutation Recently, it was shown that filaggrin expression is reduced in atopic dermatitis even in the absence of any mutation [29]. Keratinocytes differentiated in the presence of IL-4 and IL-13 exhibited significantly reduced filaggrin gene expression and neutralization of IL-4 and IL-13 improves skin barrier integrity [30]. This indicates that Th-2 lymphocytes directly contribute to the skin barrier defect in atopic dermatitis. 

Platen, G.E., Skar, M., Luthman, K. and Brandi, M. (2007) Drug permeability across a phospholipid vesicle based barrier 3. Characterization of drug-membrane interactions and the, effect of agitation on the barrier integrity and on the permeability. European Journal of Pharmaceutical Sciences, 30, 324—332. 

All the above-mentioned changes in lipid composition and organization in diseased and dry skin likely contribute to an impaired stratum corneum barrier function and increased susceptibility to dry skin. However, as previously indicated, abnormalities in the process of envelope formation may also strongly influence the stratum corneum barrier integrity. Therefore, more information is required to elucidate the precise mechanisms by which stratum corneum structure and function are altered. 

Cumulative (8 h) Passive and lontophoretic Lidocaine Transport through Porcine Skin as a Function of Barrier Integrity... 

Barrier Integrity (Relative TEWL) Passive Iontophoresis... 

Within all of these procedures, the actual measurements continue to focus on mildness and moisturization as defined by the same three aspects used in short-term tests, sensory, visible appearance, and hydration state, with the addition of a measure of barrier integrity using TEWL. 

Gon, Y., Wood, M. R., Kiosses, W. B., Jo, E., Sanna, M. G., Chun, J., and Rosen, H. (2005). S1P3 receptor-induced reorganization of epithelial tight junctions compromises lung barrier integrity and is potentiated by TNF. Proc. Natl. Acad. Sci. USA 102(26), 9270-9275. 

Related to the post-traumatic microvascular damage is the pathophysiological process of vasogenic brain edema that represents a disruption of blood-brain barrier integrity, resulting in sodium and protein accumulation and osmotic fluid expansion of the brain extracellular space. Clinically, this is reflected by an increase in intracranial pressure which, if unchecked, can cause secondary compressive injury to vital brain structures. 

Lawrence, J.N. (1997). Electrical resistance and tritiated water permeability as indicators of barrier integrity of in vitro human skin, Toxicol In Vitro, 11, 241-249. 

Beauchesne E, Desjardins P, HazeU AS, Butterworth RE (2009) eNOS gene deletion restores blood-brain barrier integrity and attenuates neurodegeneration in the thiamine-deficient mouse brain. J Neurochem 111 452-459... 

Fig. 24 Three different capacitor structures according to the (a) node, (b) concave and (c) buried barrier integration schemes.

Kanmogne GD, Schall K, Leibhart J, Knipe B, Gendelman HE, Per-sidsky Y (2007) HIV-1 gpl20 compromises blood-brain barrier integrity and enliance monocyte migi ation across blood-brain barrier Implication for viral neuropathogenesis. J Cereb Blood Plow Metab 27 123-134. 

Nygaard, S.D., Ganz, T. and Peterson, M.W. (1993). Defensins reduce the barrier integrity of a cultured epithelial monolayer without cytotoxicity. Am. J. Respir. Cell Mol. Biol. 8, 193-200. 

Barrier integrity Preparation and storage conditions, follicles and other holes, viability (metabolic capacity)... 

Receptor fluid Solubility, maintenance of skin viability/ barrier integrity... 

Fenart L, Buee-Scherrer V, Descamps L, Duhem C, Poullain MG, et al. 1998. Inhibition of P-glycoprotein rapid assessment of its implication in blood-brain barrier integrity and drug transport to the brain by an in vitro model of the blood-brain barrier. Pharm. Res. 15(7) 993-1000... 

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