There is good evidence to support the use of PEG, tegaserod, lactulose, and psyllium. Surprisingly, there is a paucity of trials for many commonly used agents. These aspects should be considered when designing trials comparing new agents with traditional therapies because their use may not be well validated.

The pylorus controls the flow between a reservoir dedicated to mechanical and chemical digestion (the stomach) and a conduit dedicated to the absorption of nutrients (the intestines). The pylorus adjusts gastric outflow resistance to physiological needs. It allows the outflow of isotonic fluids yet selectively retains particles too large for delivery to the intestines and in concert with the antrum further processes them (gastric sieving). Unlike most gut sphincters, the pylorus, at least of man, maintains a patent lumen most of the time. It only intermittently becomes a tightly closed barrier that arrests all flow out of and into the stomach. The geometry of the pylorus changes dramatically from the relaxed open state to closure. Pyloric closure involves contraction of its proximal and distal muscle loops, and occlusion of its lumen by mucosal folds. Current studies that combine pressure recordings with imaging by magnetic resonance imaging or ultrasound and fluid-mechanical analysis shed new light on the role of the pylorus in gastric emptying and digestion. Much has been learned in recent years on the innervation of the normal pylorus particularly from studies on infantile hypertrophic stenosis, and attempts are being made to treat gastroparesis by interventions on the pylorus.

Drugs may be designed that specifically act on 5-HT3, cholecystokinin, or TNF-alpha receptors. Spatiotemporal maps should boost the diagnostic yield from dynamic imaging of motility using ultrasound, computed axial tomography scan, or MRI and the understanding of the mechanical forces driving digestion. Symptomatic benefit in gastroparesis may derive more from improved accommodation than gastric emptying.

No abstract

Cancer cells respond to matrix mechanical stiffness in a complex manner using a coordinated, hierarchical mechano-chemical system composed of adhesion receptors and associated signal transduction membrane proteins, the cytoskeletal architecture, and molecular motors. Mechanosensitivity of different cancer cells in vitro are investigated primarily with immortalized cell lines or murine derived primary cells, not with primary human cancer cells. Hence, little is known about the mechanosensitivity of primary human colon cancer cells in vitro. Here, an optimized protocol is developed that describes the isolation of primary human colon cells from healthy and cancerous surgical human tissue samples. Isolated colon cells are then successfully cultured on soft (2 kPa stiffness) and stiff (10 kPa stiffness) polyacrylamide hydrogels and rigid polystyrene (~3.6 GPa stiffness) substrates functionalized by an extracellular matrix (fibronectin in this case). Fluorescent microbeads are embedded in soft gels near the cell culture surface, and traction assay is performed to assess cellular contractile stresses using free open access software. In addition, immunofluorescence microscopy on different stiffness substrates provides useful information about primary cell morphology, cytoskeleton organization and vinculin containing focal adhesions as a function of substrate rigidity.