Facilitated diffusion by iontophoresis of vasoactive agents to the rat incisor pulp

The use of iontophoresis for facilitated diffusion of vasoactive agents into the dental pulp was investigated in lower incisor teeth of anaesthetized rats. Acetylcholine, carbachol and noradrenaline were iontophoresed with anodal and sodium nitroprusside with cathodal direct current through a superficial dentin exposure. Pulpal blood flow was measured with laser Doppler flowmetry. Current intensities below 100 microA of both polarities, using sodium chloride as a medium, caused no or minor afferent nerve-induced vasodilation, but excited sympathetic fibres of the pulp in a current-dependent manner. The current threshold for facilitated diffusion of acetylcholine was about 20 microA. The vascular responses to the cholinergic and noradrenergic drugs appeared within a minute after the onset of current and they were abolished by systemic administration of atropine and phenoxy benzamine, respectively. Iontophoresis of acetylcholine (40-100 microA for 20-120 s) caused a 3-fold increase of pulpal blood flow which was not dose-dependent; carbachol provoked a high-magnitude, long-lasting vasodilation and so did sodium nitroprusside. Noradrenaline caused a long-lasting vasoconstriction. In denervated rats iontophoresis of carbachol had effects similar to those seen in intact animals. None of the drugs used locally had any effect on systemic blood pressure. The results of this study indicate that iontophoresis can be used for delivery of vasoactive agents from an exposed dentin surface into the pulp in sufficient quantity to elicit drug-specific local vascular responses without causing systemic vascular effects.     

Diffraction correction methods for insertion ultrasound attenuationestimation

Diffraction effects in acoustic ultrasound attenuation coefficient estimation using an insertion technique are described. The estimation error produced by diffraction is characterized as a function of distance and nominal attenuation values. Two methods for correcting for the diffraction effect, termed the theoretical diffraction correction and experimental diffraction correction techniques, respectively, are presented. Experimental validation of the two techniques, using two different sets of ultrasound measurements obtained with 1-MHz and 500-kHz transducer pairs, respectively, is also presented. Significant improvement in the accuracy of the acoustic attenuation coefficient is demonstrated for both techniques     

Protein phosphatases limit tumor motility

Elevators of cAMP, such as prostaglandin E2 (PGE2), activate protein kinase A (PKA) and induce PKA-stimulated motility and metastasis by metastatic Lewis lung carcinoma cells (LLC-LN7). Non-metastatic LLC (LLC-C8) are unresponsive to cAMP elevation even though they are not deficient in the PKA enzymes. To determine whether this PKA unresponsiveness might be due to increased dephosphorylation by serine/threonine protein phosphatases (PP-1/2A) within non-metastatic LLC-C8, the effects of the PP-1/2A inhibitor okadaic acid on the migration and invasion by non-metastatic LLC-C8 cells was measured. Okadaic acid stimulated motility of non-metastatic LLC-C8 cells to a level that was comparable to that of metastatic LLC-LN7 cells. PGE2 further increased the motility of the non-metastatic LLC-C8 cells when okadaic acid was present, although not in the absence of okadaic acid. The stimulation of motility by okadaic acid was diminished when PKA activity was inhibited. Dose-response studies with concentrations of okadaic acid that selectively inhibited PP-2A or both PP-2A and PP-1 showed a progressive increase in migration of non-metastatic LLC-C8 cells, suggesting that both PP-1 and PP-2A limit their motility. By contrast, metastatic LLC-LN7 cells were more motile than were non-metastatic LLC-C8 cells, but this motility was only marginally affected by okadaic acid. Comparisons of the levels of PP-1/2A enzyme activities in the LLC variants showed more activity in non-metastatic LLC-C8 than in metastatic LLC-LN7 cells. The identity of the PP whose activity was increased in the non-metastatic LLC-C8 was assessed by using okadaic acid, which selectively inhibits PP-2A activity at low concentrations and PP-1 and PP-2A at high concentrations, and calyculin A, which inhibits PP-2A at a similar concentration to that affected by okadaic acid but is more potent at inhibiting PP-1. The inhibition of PP activities by okadaic acid and by calyculin A showed a pattern which suggested the presence both of PP-1 and of PP-2A in non-metastatic LLC-C8 cells, but the presence of PP-1 and a reduction in PP-2A in metastatic LLC-LN7 cells. The sum of these data suggests that PKA-stimulated motility is restricted both by PP-1 and by PP-2A in non-metastatic LLC, and that a deficiency in this restriction results in increased migration and invasion.     

Day by day: Playing and learning.

Discussion of the inherent value of youngsters' play highlights significant factors to consider when interacting with children in a variety of contexts. Appropriate play activities can provide optimal opportunities for healthy cognitive and socioemotional development. Presentation of several case examples illustrates the importance of integrating play in child development programs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)