However, the ability of the dose of LANZO used in this study to induce in vivo inhibition of proton pumps extragastrically has not been thoroughly investigated. We hypothesize that the mechanisms by which combined LANZO and prednisolone treatment improve the dystrophic phenotype in mdx mice may include: 1) reduced inflammatory cell recruitment to the skeletal muscle; 2) altered ion conductivity of skeletal muscle Na + /K + -ATPase and chloride ion channels; 3) decreased apoptotic signaling cascades promoting myonecrosis. Off-label use of LANZO has been more thoroughly investigated in the treatment of cancer, wherein LANZO has been suggested to have anti-inflammatory and anti-metastatic effects. De Milito et al. observed that PPI administration promotes B cell apoptosis in acute B cell lymphatic leukemia via A 987306 altering tumor lysosomes and extracellular pH. The anti-metastatic effects of LANZO administration are also supported by a Phase I/II trial by Spungnini et al. who observed improved tumor outcomes in animals receiving combined treatment of LANZO and chemotherapeutics. Another putative beneficial effect of LANZO on the dystrophic phenotype may be due to its anti-inflammatory properties. Macrophage pre-treatment with LANZO decreases nitric oxide synthesis and cell viability in response to stimulation by LPS. Further, pretreatment of monocytes with LANZO has been shown to decrease LPS-induced TNFa and IL-1b expression via decreasing IkB-a and ERK phosphorylation. A similar PPI, omeprazole, has been shown to decrease neutrophil chemotaxis and ROS production. Further, omeprazole has been shown to decrease peripheral blood neutrophil phagocytic activity and oxidation 4 hours after oral administration in healthy human subjects. Since the mechanisms of actions between different classes of PPI are similar, we hypothesize that oral LANZO administration may attenuate the dystrophic phenotype in mdx mice by Acephate reducing neutrophil recruitment and respiratory burst and by skewing of muscle macrophages away from a proinflammatory M1 macrophage phenotype. This is supported as populations of iNOS expressing muscle macrophages have been suggested to contribute to muscle cell lysis in mdx mice and shifts in muscle macrophage activation from a proinflammatory to anti-inflammatory/ regenerative phenotype improve dystrophic pathology. Further, depletion of neutrophils has been shown to attenuate components of the dystrophic phenotype in mdx mice. Linear chromosomes are capped by telomeres, nucleoprotein structures that protect chromosome ends from nuclease digestion. Telomeres are comprised of simple DNA repeats and are packaged in a sequence-specific manner with the six-member protein complex known as shelterin. Incomplete DNA replication at chromosome ends causes the loss of telomeric DNA with each cell division. Telomeric DNA loss is cumulative and is tolerated until telomeres reach a critically short length.