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Interlocking Inequalities Related to Water and Sanitation, Nutrition and Healthcare Access
Published in Oliver Cumming, Tom Slaymaker, Equality in Water and Sanitation Services, 2018
Access to healthcare is important for obtaining preventive care (e.g. nutritional supplements and vaccines), health education (e.g. exclusive breastfeeding, child nutrition, and the importance of hygiene during child care), and treatment for diseases and malnutrition. Zinc supplements are effective in promoting linear growth and preventing stunting.33 Zinc and vitamin A supplements have been linked with decreased intestinal permeability, a contributor to malabsorption in EED.34 Access to routine immunizations, rotavirus, cholera and new ETEC and Shigella vaccines could be especially critical for undernourished children by preventing diarrhea,35 although the impact on EED on vaccine effectiveness needs further investigation.36
Circulating markers of intestinal barrier injury and inflammation following exertion in hypobaric hypoxia
Published in European Journal of Sport Science, 2023
Zachary J. McKenna, Bryanne N. Bellovary, Jeremy B. Ducharme, Michael R. Deyhle, Andrew D. Wells, Zachary J. Fennel, Jonathan W. Specht, Jonathan M. Houck, Trevor J. Mayschak, Christine M. Mermier
Under normal physiological conditions the intestinal epithelium operates in a state of “physiologic hypoxia”, often characterized as a steep oxygen gradient from the submucosa to the intestinal lumen (Konjar et al., 2021; Singhal & Shah, 2020; Zheng et al., 2015). Indeed, this physiologic hypoxia allows for several intracellular adaptations that collectively promote intestinal barrier homeostasis via hypoxia inducible factors (Konjar et al., 2021; Singhal & Shah, 2020; Zheng et al., 2015). However, in some scenarios this hypoxia can become pathological resulting in intestinal injury and inflammation (Singhal & Shah, 2020). High altitude exposures can reduce splanchnic perfusion (Loshbaugh et al., 2006) and lower blood oxygen levels causing local hypoxic and oxidative stress in the gut (Dosek et al., 2007). These stressors can injure the intestinal barrier leading to increased intestinal permeability and bacterial endotoxin translocation (Lian et al., 2021; McKenna et al., 2022b). The translocation of Gram-negative bacteria which harbor lipopolysaccharides (LPS) on their outer membrane can activate innate immune cells via Toll like receptor-4 (TLR-4) to initiate local and systemic inflammatory responses (Ducharme et al., 2022). Indeed, residence at high altitude has been shown to damage the intestinal barrier and increase intestinal permeability (Karl et al., 2018). Subsequent LPS-mediated increases in pro-inflammatory cytokines could cross the blood brain barrier and contribute to central nervous system dysfunction which may be a contributing factor to development of AMS (Banks et al., 1995).
Toxicological and pharmacokinetic properties of sucralose-6-acetate and its parent sucralose: in vitro screening assays
Published in Journal of Toxicology and Environmental Health, Part B, 2023
Susan S. Schiffman, Elizabeth H. Scholl, Terrence S. Furey, H. Troy Nagle
The assessment of transepithelial electrical resistance (TEER) and permeability in human transverse colon epithelium in the current in vitro study found that sucralose-6-acetate and sucralose both disrupt gastrointestinal epithelial tight junctions and mucosal barrier function at mM concentrations in the absence of bacteria. A significant collapse of TEER occurred after a single 24-hr exposure to 40 mM sucralose which is only 6.7-fold greater than the concentration of sucralose currently approved by the European Union (2004) for use in a single syrup-type food supplement at 2400 mg/kg (6 mM). Integrity of the intestinal epithelial barrier is dependent upon tight junctions, the specialized complexes which connect adjacent cells and provide a physical and functional barrier that limits or regulates passive diffusion of ions, solutes, macromolecules, and cells from the lumen through the paracellular space. Sucralose-6-acetate and sucralose reduced the transepithelial resistance and enabled ions and macromolecules to pass from the apical (luminal) to the basolateral side of intestinal epithelium through the paracellular pathways. Enhanced intestinal permeability (leaky gut) that enables passage of microorganisms and metabolites into the body plays a major role in IBD (Lee 2015; Welcker et al. 2004), chronic liver disease (Mohandas and Vairappan 2017), as well as pathogenesis of colorectal cancer (Sánchez-Alcoholado et al. 2020). Further, elevated intestinal permeability in conjunction with repeated ingestion and retention of colonic contents over days may increase intraluminal concentration, absorption, and systemic exposure to sucralose and sucralose-6-acetate resulting long-term in bioaccumulation and toxicity.