Preparation of faculty members and students to be citizen leaders and pharmacy advocates.

To identify characteristics and quality indicators of best practices for leadership and advocacy development in pharmacy education, a national task force on leadership development in pharmacy invited colleges and schools to complete a phone survey to characterize the courses, processes, and noteworthy practices for leadership and advocacy development at their institution. The literature was consulted to corroborate survey findings and identify additional best practices. Recommendations were derived from the survey results and literature review, as well as from the experience and expertise of task force members. Fifty-four institutions provided information about lecture-based and experiential curricular and noncurricular components of leadership and advocacy development. Successful programs have a supportive institutional culture, faculty and alumni role models, administrative and/or financial support, and a cocurricular thread of activities. Leadership and advocacy development for student pharmacists is increasingly important. The recommendations and suggestions provided can facilitate leadership and advocacy development at other colleges and schools of pharmacy.

Adenosine sensory transduction pathways contribute to activation of the sensory irritation response to inspired irritant vapors.

The molecular mechanisms through which sensory irritants stimulate nasal trigeminal nerves are poorly understood. The current study was aimed at evaluating the potential contribution of purinergic sensory transduction pathways in this process. Aerosols of 4-36 mM adenosine 5'-triphosphate (ATP) and adenosine both acted as sensory irritants. Large dose capsaicin pretreatment to induce degeneration of transient receptor potential vanilloid type-1 (TRPV1)-expressing C fibers greatly reduced, but did not abolish, the sensory irritation response to ATP aerosol and was without effect on the response to adenosine aerosol, indicating that ATP acts largely on capsaicin-sensitive (primarily C fibers) and adenosine acts on capsaicin-insensitive (primarily Adelta fibers) nerves. The response to adenosine was diminished by pretreatment with the broad-based adenosine receptor antagonist theophylline (20 mg/kg) and A1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.1 mg/kg), providing evidence that adenosine stimulates capsaicin-insensitive nerves via the A1 receptor. The sensory irritation responses to 275 ppm styrene and 110 ppm acetic acid vapors were significantly reduced by theophylline pretreatment suggesting a role for adenosine signaling pathways in activation of the sensory irritant response by these vapors. If sensory nerves are activated by mediators that are released from injured airway mucosal cells, then nasal sensory nerve activation may be a reflection of irritant-induced alterations in airway cell integrity.

Lack of role for the vanilloid receptor in response to several inspired irritant air pollutants in the C57Bl/6J mouse.

Sensory irritants initiate respiratory reflexes by stimulating trigeminal sensory nerves. The vanilloid receptor (TRPV1) is expressed on sensory C fibers. The current experiments were aimed at examining the role of this receptor in mediating responses to several airborne irritants including an acidic (acetic acid), electrophilic (acrolein), and lipophilic solvent (styrene) vapor. Wild-type (C57Bl/6J) and VR1 knockout [B6.129S4-VR1(tm1jul)] mice were exposed to these irritants and breathing pattern responses were assessed by plethysmographic techniques; both wild-type and knockout animals responded similarly to the irritants. The TRPV1 antagonist iodoresiniferatoxin was also without effect on the responses to the irritants. Thus, in the C57Bl/6J mouse the TRPV1 receptor does not appear to play a major role in the stimulation of nasal trigeminal central reflex responses by these irritant air pollutants.

Sulfate- and size-dependent polysaccharide modulation of AMPA receptor properties.

Previous work found evidence that alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors interact with and are functionally regulated by the glycosaminoglycan heparin. The present study tested whether dextran species affect ligand binding, channel kinetics, and calcium permeability of AMPA receptors. Dextran sulfate of 500 kDa markedly reduced high affinity [3H]AMPA binding in solubilized hippocampal membranes. In isolated receptors reconstituted in a lipid bilayer, the same dextran sulfate prolonged the lifetime of open states exhibited by AMPA-induced channel fluctuations. The large polysaccharide further changed the single channel kinetics by increasing the open channel probability five- to sixfold. Such modulation of channel activity corresponded with enhanced levels of calcium influx as shown in hippocampal neurons loaded with Fluo3AM dye. With an exposure time of <1 min, AMPA produced a dose-dependent increase in intracellular calcium that was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX). Dextran sulfate, at the same concentration range that modified ligand binding (EC50 of 5-10 nM), enhanced the AMPA-induced calcium influx by as much as 60%. The enhanced influx was blocked by CNQX, although unchanged by the N-methyl-D-aspartate (NMDA) receptor antagonist AP5. Confocal microscopy showed that the increase in calcium occurred in neuronal cell bodies and their processes. Interestingly, smaller 5-8-kDa dextran sulfate and a non-sulfated dextran of 500 kDa had little or no effect on the binding, channel, and calcium permeability properties. Together, these findings suggest that synaptic polysaccharide species modulate hippocampal AMPA receptors in a sulfate- and size-dependent manner.