Barrier function

Soap as used in personal cleansing products has a long safe history of use. Modem soaps have been specifically formulated to be compatible with skin and to be used on a daily basis with minimal side effects. Excessive use of soap for skin cleansing can dismpt the natural barrier function of skin through the removal of skin oils and dismption of the Hpid bdayer in skin. This can result in imperfect desquamation or a dry appearance to skin and cause an irritation response or erythema, ie, reddening of the skin. Neither of these is a permanent response and the eHcitation of this type of skin reaction depends on the individual s skin type, the product formulation, and the frequency of use. 

GPR4 SPC, LPC Migration, angiogenesis, impairment of endothelial barrier function... 

Brinkmann V, Cyster JG, Hla T (2004) FTY720 sphingosine 1-phosphate receptor-1 in the control of lymphocyte egress and endothelial barrier function. Am J Transplant 4 1019-1025... 

Evaluation of inhibition of the other isoforms is still in the preclinical stages. Inhibition of NHE2 with prostaglandin E2 or with amiloride hastens the reestablishment of barrier function after intestinal ischemic damage in pigs and the use of S-3226 in rats with renal ischemia improved outcomes. Further work examining the effect of inhibition of the other isoforms is still required. 

A great deal of our current understanding of the structure and function of the outer membrane of Gram-negative bacteria has come from studies with Escherichia coli and Salmonella typhimurium. The permeability barrier function of the outer membrane can... 

Raith and Neubert [57] have developed a method for the profihng of human stratum comeum ceramides. The method enables the investigation of the role of ceramides in maintaining the barrier function of stratum comeum. TLC using automated multiple development was modified for semipreparative purposes. The fractionation of complex lipid extracts using this method ensured specific, sensitive, and... 

M. Marra Fell, Lipid Phase Contributions to Bilayer Barrier Function, Ph.D. dissertation. University of Utah, Salt Lake City, UT, 1995. 

General functions of the skin are outlined in Table 1. These functions include containment of tissues and organs, multifaceted protections, environmental sensing, and body temperature regulation. Some skin functions are inextricably entwined. For instance, containment and the barrier functions are to some extent inseparable. Active sweating is accompanied by increased peripheral blood flow, which in turn is tied in with greater nourishment of the cells of the skin as needed to promote their proliferation, differentiation, and specialization. 

Containment of body fluids and tissues Protection from harmful external stimuli (barrier functions)... 

The skin s main physiological roles are outlined in Table 1. Of these, the chemical barrier function is central to the use of topical drugs because deposition... 

The amounts of ointments and creams people apply are highly individualized. So are the techniques of application. Some patients vigorously rub semisolid formulations into the skin, while others just spread films until they are more or less uniform over the desired area. While pharmacokinetic assessments of a system s delivery attributes is ordinarily done using normal skin (in vitro) or on healthy volunteers (in vivo), the site of its clinical deployment is usually anything but normal. Rather, it is determined by the skin condition to be treated. Clearly, the manufacturer is without control over how a disease is expressed in a particular patient. For many diseases, disease manifestation can be anywhere on the body. Moreover, from individual to individual it varies in intensity and vastness. Thus, more area may be involved in one case than in another, and the barrier function of the skin may be more or less intact in any instance. This creates a set of imponderables with respect to delivery, efficacy, and safety. 

The significance of the barrier function of membranes has been the topic of considerable research. The blood-brain barrier and the blood-retinal barrier are well understood, and the microscopic structures imparting and controlling barrier properties have been quite thoroughly investigated and the science reviewed [15, 154-155], The structures and functions of ocular membranes specific to transport associated with ophthalmic drug administration also have been topics of extensive research [15, 157-158],... 

Kramer, S. D. Begley, D. J. Abbott, N. J., Relevance of cell membrane hpid composition to blood-brain barrier function Lipids and fatty acids of different BBB models, Am. Assoc. Pharm. Sci. Ann. Mtg., 1999. 

An appropriate starting point for any discussion of drug transport in the gastrointestinal (GI) tract at the cellular level requires some introductory remarks on the structure and function of GI tissue. As a class of tissue, epithelia demarcate body entry points (skin, eye, respiratory, urinary, and GI organ systems), predisposing a general barrier function with respect to solute entry and translocation. In addi-... 

FGJ Poelma, R Breas, JJ Tukker. Intestinal absorption of drugs. IV. The influence of taurocholate and L-cysteine on the barrier function of mucus. Int J Pharm 64 161-169, 1990. 

DW Powell. Barrier function of epithelia. Am J Physiol 241 G275-G288, 1981. 

Watkins PB. (1997). The barrier function of CYP3A4 and P-glycoprotein in the small bowel. Adv Drug Delivery Rev 27 161-170. 

Moorhouse SR, Carden S, Drewitt PN, et al. 1988. The effect of chronic low level lead exposure on blood-brain barrier function in the developing rat. Biochem Pharmacol 37 4539-4547. 

Azghani, A.O., Gray, L.D. and Johnson, AR. (1993) A bacterial protease perturbs the paracellular barrier function of transporting epithelial cell monolayers in culture. Infection and Immunity 61, 2681-2686. 

Kindon, H., Pothoulakis, C., Thim, L., Lynch-Devaney, K. and Podolsky, D.K. (1995) Trefoil peptide protection of intestinal epithelial barrier function cooperative interaction with mucin glycoprotein. Gastroenterobgy 109, 516-523. 

Culture protocols have been published which describes an accelerated differentiation process where monolayers are ready to be used after 3-7 days of culture [90-92]. One of these systems, the so-called BD BioCoat Intestinal Epithelium Differentiation Environment, is commercially available through BD Bioscience. This system is described to produce monolayers of a quality that are comparable with the typical Caco-2 cells with respect to permeability for drugs transported transcellularly. The paracellular barrier function is however low, as indicated by high mannitol permeability and low TER. The functional capacity for active uptake and efflux is not as thoroughly characterized as for the standard Caco-2 mono-layers. 

Modified mammalian cell systems for the study of the role of transporters and/or metabolism in oral absorption consists of two main components the cell line and the vector bearing a cDNA encoding the protein of interest. The cell line serves two roles first, to support adequate expression of the cDNA and second, to provide a barrier function which is generally critical in assays for transporter function. 

The role of lipids on absorption has been extensively reviewed by Porter and Charman [29, 30]. The influences are diverse and include effects on luminal drug solubility, altering the metabolic and barrier function of the intestinal wall, stimulating lymphatic transport and a reduction in gastric transit, thereby increasing the time available for dissolution. 

Garcia-Rodenas C.L., Bergonzelli G.E., Nutten S., Schumsnn A., Cherbut C., Turini M., Omstein K., Rochat F. and Corthesy-Theulaz I. (2006). Nutritional approach to restore impaired intestinal barrier function and growth after neonatal stress in rats . 7 Pediatr Gastroenterol Nutr, 43(1), 16-24. 

Intestinal infections that cause persistent diarrhea normally result in histopathological changes to the intestine including villus blunting, crypt hypertrophy and inflammatory infiltrate in the lamina propria. These histopathological disarrangements are seen in Cryptosporidium, Cy-clospora and microsporidial infections [28], Furthermore, it has been documented that there are substantial disruptions of intestinal barrier function as measured by lactu-lose mannitol permeability ratios in patients with AIDS... 

Among functional alterations in patients with infectious diarrhea are increased secretion, failure of barrier function and reduction of absorptive function causing dehydration and nutritional deficiency. An understanding of the molecular pathogenesis with regard to each enteric pathogen will likely lead to a quicker diagnosis, more effective treatment and prevention of enteric infections. 

Lima AAM, Silva TJ, Gifoni AMR, Barrett LJ, McAuliffe IT, Bao Y, Fox JW, Fedorko DP, Guerrant RL Mucosal injury and disruption of intestinal barrier function in HIV-infected individuals with and without diarrhea and cryptosporidiosis in Northeast Brazil. Am J Gastroenterol 1997 92 1861-1866. 

The leading hypothesis for the development of chronic intestinal inflammation is that an abnormal immune response to normal flora might be crucial. This loss of tolerance might be due to a lack of regulatory mediators or cells, or a breakdown in barrier function which makes possible the access of inflammatory bacterial products to the local immune system, thereby overwhelming the normal regulation [3], These possibilities were supported by... 

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