Comparison of the chloride channel activator lubiprostone and the oral laxative Polyethylene Glycol 3350 on mucosal barrier repair in ischemic-injured porcine intestine.

AIM: To investigate the effects of lubiprostone and Polyethylene Glycol 3350 (PEG) on mucosal barrier repair in ischemic-injured porcine intestine. METHODS: Ileum from 6 piglets (approximately 15 kg body weight) was subjected to ischemic conditions by occluding the local mesenteric circulation for 45 min in vivo. Ileal tissues from each pig were then harvested and mounted in Ussing chambers and bathed in oxygenated Ringer's solution in vitro. Intestinal barrier function was assessed by measuring transepithelial electrical resistance (TER) and mucosal-to-serosal fluxes of (3)H-mannitol and (14)C-inulin. Statistical analyses of data collected over a 120-min time course included 2-way ANOVA for the effects of time and treatment on indices of barrier function. RESULTS: Application of 1 micromol/L lubiprostone to the mucosal surface of ischemic-injured ileum in vitro induced significant elevations in TER compared to non-treated tissue. Lubiprostone also reduced mucosal-to-serosal fluxes of (3)H-mannitol and (14)C-inulin. Alternatively, application of a polyethylene laxative (PEG, 20 mmol/L) to the mucosal surface of ischemic tissues significantly increased flux of (3)H-mannitol and (14)C-inulin. CONCLUSION: This experiment demonstrates that lubiprostone stimulates recovery of barrier function in ischemic intestinal tissues whereas the PEG laxative had deleterious effects on mucosal repair. These results suggest that, unlike osmotic laxatives, lubiprostone stimulates repair of the injured intestinal barrier.

Spatial distribution of inhibitory synaptic connections during development of ferret primary visual cortex.

Intracortical inhibition in the primary visual cortex plays an important role in creating properties like orientation and direction selectivity. However, the development of the spatial pattern of inhibitory connections is largely unexplored. This was investigated in the present study. Tangential slices of layers 2/3 of ferret striate cortex were prepared for whole-cell patch clamp recordings, and presynaptic inhibitory inputs to pyramidal neurons were scanned by local photolysis of Nmoc-caged glutamate. Inhibitory synaptic currents (IPSCs) were first detected around postnatal day (P) 17. They originated locally around the recorded cells. Both the number and the total areas supplying the inhibitory inputs increased thereafter and peaked at the time around and shortly after eye opening (P29-37). A refinement period then followed in which the areas providing the majority of inhibitory inputs shrank from 600 microm around the recorded neurons to 200-300 microm in more mature animals (>/=P38). The amplitude of IPSCs increased progressively with increasing age. Long-range inhibitory inputs (>600 microm) were present around eye opening and they often developed into a clustered patchy pattern in more mature animals (>/=P38). In summary, our results show a refinement and clustering in the spatial pattern of inhibitory connections during postnatal development of ferret visual cortex.

Different inhibitory synaptic input patterns in excitatory and inhibitory layer 4 neurons of ferret visual cortex.

The synaptic mechanisms underlying the generation of orientation and direction selectivity in layer 4 of the primary visual cortex are still largely unclear. Previous in vivo work has shown that intra-cortical inhibition plays a major role in generating the properties of orientation and direction selectivity. Excitatory and inhibitory cortical neurons differ in their receptive field properties: excitatory neurons tend to be orientation- and direction-selective, inhibitory neurons tend to be orientation-, but not direction-selective. Here we have compared the relationship between direction preference maps recorded in vivo and synaptic input maps recorded in vitro from excitatory and inhibitory stellate cells in layer 4 of ferret visual cortex. Our goal was to test whether the differences in direction tuning between these cell populations might result from different inhibitory connectivity patterns. We found that excitatory neurons, which are direction tuned in vivo, receive approximately 50% of their inhibitory inputs from cortical regions of opposite direction preference whereas inhibitory cells, which are not or poorly direction tuned, receive only very few inputs from regions of opposite direction preference. This confirms that inhibitory connections arising in cortical regions of opposite direction preference may be required to create or strengthen direction tuning in their target neurons. Thus, differences in intracortical inhibitory circuit patterns may underlie the differences in receptive field properties observed between excitatory and inhibitory neurons in vivo.