Experiments to determine the site of slow-wave origin and the mechanism of propagation were performed on muscles of the canine proximal colon. Cells along the submucosal border of the circular layer had resting membrane potentials (RMP) averaging -78 mV, and slow waves, 40 mV in amplitude. The RMP of cells through the thickness of the circular layer decreased exponentially with distance from the submucosal border, such that RMPs of circular cells at the myenteric border were only -43 mV. Slow waves decreased in amplitude through the thickness such that slow waves could not be detected adjacent to the myenteric border. When a thin strip of muscle along the submucosal border was removed, slow waves were not recorded from the bulk of the circular layer and could not be evoked by acetylcholine. Slow waves were still present in the excised strip. Experiments to determine the rate of slow-wave propagation were also performed. Two cells were impaled, one at the submucosal surface, and another at some distance through the circular layer. Slow waves occurred nearly simultaneously at both sites. What latency was observed could be explained on the basis of electrotonic conduction. The results support the hypothesis that in the canine proximal colon slow waves are generated at the extreme submucosal surface of the circular layer. The bulk of the circular layer does not possess either pacemaker or regenerative mechanisms, and slow waves propagate passively toward the myenteric border. The cable properties of the circular muscle syncytium furnish a barrier to invasion of the longitudinal layer by the slow wave event.

Experiments were performed to determine the source of the 20 cycles/min electrical oscillation commonly seen in colonic electrical records, the influence of the 20 cycles/min rhythm on the circular and longitudinal muscle layers, and the interactions between the 20 cycles/min rhythm and slow waves in circular muscle cells. Cross-sectional muscle preparations of the canine proximal colon were used to allow impalement of cells at any point through the thickness of the muscularis. Intracellular recordings from circular muscle cells clearly showed the two characteristic pacemaker frequencies in the colon (6 cycles/min slow waves; 20 cycles/min oscillations). The 20 cycles/min oscillations were recorded from longitudinal and circular muscle cells. Their amplitudes were greatest at the myenteric border. In the longitudinal layer the 20 cycles/min events initiated action potentials; in circular muscle the 20 cycles/min events summed with slow waves. Simultaneous recordings from circular and longitudinal cells across the myenteric border demonstrated that events in the two layers were usually in phase, suggesting that the two layers are electrically coupled and are paced by a common pacemaker. The amplitude of the 20 cycles/min events decayed with distance from the myenteric border in both circular and longitudinal muscles. The data demonstrate that two discrete populations of pacemaker cells generate the spontaneous electrical activity in the colon. Both events appear to passively spread through the circular muscle. It is the summation of these events that appears to serve as the signal for excitation-contraction coupling in circular muscle.

Huntington disease is a neurodegenerative disorder that involves preferential atrophy in the striatal complex and related subcortical nuclei. In this paper, which is based on a dataset extracted from the PREDICT-HD study, we use statistical shape analysis with deformation markers obtained through Large Deformation Diffeomorphic Metric Mapping of cortical surfaces to highlight specific atrophy patterns in the caudate, putamen, and globus pallidus, at different prodromal stages of the disease. Based on the relation to cortico-basal-ganglia circuitry, we propose that statistical shape analysis, along with other structural and functional imaging studies, may help expand our understanding of the brain circuitry affected and other aspects of the neurobiology of HD, and also guide the most effective strategies for intervention.

The suppression of human immunodeficiency virus (HIV) replication and elevation in CD4 cells observed with protease inhibitor combination regimens known as HAART (highly active antiretroviral therapy) may allow AIDS patients to undergo an immune recovery that allows them to suppress the progression of cytomegalovirus (CMV) retinitis. Eleven AIDS patients receiving HAART with healed CMV retinitis in whom CMV-specific maintenance therapy was discontinued were studied. Median CD4 cell counts were 42 before the initiation of HAART and 183 at discontinuation of anti-CMV therapy. While a median 1.1 log 10 drop in plasma HIV-1 RNA was obtained between starting HAART and withdrawal of maintenance therapy for CMV, only 3 of 11 patients maintained plasma HIV RNA below the limits of detection. Reactivation of CMV retinitis after withdrawal of anti-CMV therapy did not occur in any of the patients observed for a median of 156 days (range, 92 -558).

Traumatic brain injury (TBI) results in learning and memory dysfunction. Cognitive deficits result from cellular and metabolic dysfunction after injury, including decreased cerebral glucose uptake and inflammation. This study assessed the ability of intranasal insulin to increase cerebral glucose uptake after injury, reduce lesion volume, improve memory and learning function and reduce inflammation. Adult male rats received a controlled cortical impact (CCI) injury followed by intranasal insulin or saline treatment daily for 14 days. PET imaging of [18F]-FDG uptake was performed at baseline and at 48 h and 10 days post-injury and MRI on days three and nine post injury. Motor function was tested with the beam walking test. Memory function was assessed with Morris water maze. Intranasal insulin after CCI significantly improved several outcomes compared to saline. Insulin-treated animals performed better on beam walk and demonstrated significantly improved memory. A significant increase in [18F]-FDG uptake was observed in the hippocampus. Intranasal insulin also resulted in a significant decrease in hippocampus lesion volume and significantly less microglial immunolabeling in the hippocampus. These data show that intranasal insulin improves memory, increases cerebral glucose uptake and decreases neuroinflammation and hippocampal lesion volume, and may therefore be a viable therapy for TBI.