Uridine enhances neurite outgrowth in nerve growth factor-differentiated PC12 [corrected].

During rapid cell growth the availability of phospholipid precursors like cytidine triphosphate and diacylglycerol can become limiting in the formation of key membrane constituents like phosphatidylcholine. Uridine, a normal plasma constituent, can be converted to cytidine triphosphate in PC12 [corrected] cells and intact brain, and has been shown to produce a resulting increase in phosphatidylcholine synthesis. To determine whether treatments that elevate uridine availability also thereby augment membrane production, we exposed PC12 [corrected] cells which had been differentiated by nerve growth factor to various concentrations of uridine, and measured the numbers of neurites the cells produced. After 4 but not 2 days uridine significantly and dose-dependently increased the number of neurites per cell. This increase was accompanied by increases in neurite branching and in levels of the neurite proteins neurofilament M [corrected] and neurofilament 70. Uridine treatment also increased intracellular levels of cytidine triphosphate, which suggests that uridine may affect neurite outgrowth by enhancing phosphatidylcholine synthesis. Uridine may also stimulate neuritogenesis by a second mechanism, since the increase in neurite outgrowth was mimicked by exposing the cells to uridine triphosphate, and could be blocked by various drugs known to antagonize P2Y receptors (suramin; Reactive Blue 2; pyridoxal-phosphate-6-azophenyl-2',4' disulfonic acid). Treatment of the cells with uridine or uridine triphosphate stimulated their accumulation of inositol phosphates, and this effect was also blocked by pyridoxal-phosphate-6-azophenyl-2',4' disulfonic acid. Moreover, degradation of nucleotides by apyrase blocked the stimulatory effect of uridine on neuritogenesis. Taken together these data indicate that uridine can regulate the output of neurites from differentiating PC12 [corrected] cells, and suggest that it does so in two ways, i.e. both by acting through cytidine triphosphate as a precursor for phosphatidylcholine biosynthesis and through uridine triphosphate as an agonist for P2Y receptors.

Regional right ventricular endocardial motion in normal hearts and in hearts with left ventricular aneurysm: a three dimensional study.

We mapped the three dimensional (3D) regional right ventricular (RV) motion using Cine-CT in 9 normal subjects and compared it to data from 10 patients with left ventricular (LV) aneurysm. The endocardial borders were traced and the RV's reconstructed in 3D. Regional perpendicular RV systolic motion was evaluated by our 3D stroke-volume-element approach, and the circumferential and longitudinal variations determined. The normal RV is characterized by higher endocardial motion in the posterior relative to the anterior regions (p < 0.0001), and no longitudinal (apex-to-base) gradient. In hearts with LV aneurysms, similar circumferential variations in wall motion are accompanied with a longitudinal increase in systolic motion, from apex to the base (p < 0.0001). Therefore, a 3D method for measurement of RV regional motion was developed and applied to normal and LV aneurysm patients, showing that LV aneurysm causes RV motion abnormality at the apex, compensated by an increased basal motion.