The ability of the host to regulate permeability of the intestinal barrier is a critical determinant of host defense. Regulation of permeability occurs at the level of epithelial tight junctions (TJ). TJ are composed of transmembrane proteins, such as occludin, claudin, and JAM family proteins. Plaque proteins, such as zonula occludins (ZO), connect the TJ complex to F-actin and actomyosin rings regulating cytoskeletal reorganization (Fig. 1, reviewed in [1]). Several signaling pathways, such as myosin light chain kinase (MLCK), protein kinase C (PKC), mitogen-activated protein kinases (MAPK), and the Rho family of small GTPases, control the remodeling and maintenance of TJ. TJ not only regulate paracellular transport of nutrients and water, but they also provide a barrier against enteric microbes. Although the exact etiology is unknown, there is ample evidence that epithelial barrier function is compromised in inflammatory bowel disease (IBD) patients. Data from various studies using inert non-metabolized probes indicate that paracellular permeability is increased in Crohn’s Disease (CD) [2]. Furthermore, increased permeability may precede the onset of inflammation [3]. Researchers also found that enteric permeability is increased in 10–54 % of healthy, first-degree relatives of IBD patients [4, 5]. To date, several studies have associated IBD with mutations in the NOD2 gene [6, 7]. However, NOD2 penetrance of the most at-risk genotypes is low [8], and it is likely that cooperation with other genetic factors, such as TJ defects, is required for disease development. Interestingly, Buhner et al. detected increased permeability in IBD patients and family members with NOD2 mutations [9]. Altogether, these findings support the speculation that altered permeability constitutes one of several genetically determined variables that enhances the risk for developing IBD.
WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.
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Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.