Development of a Pharmacy Point-of-Dispensing Toolkit for Anthrax Post-Exposure Prophylaxis for Allegheny County Postal Workers.

CONTEXT: The Centers for Disease Control and Prevention (CDC) and the US Postal Service (USPS) consider anthrax to be a potential threat to USPS workers. A county health department-owned pharmacy supports local USPS response in the event of an exposure. The pharmacy team identified the need to review and update the local anthrax response plan. PROGRAM/POLICY: A Pharmacy Point-of-Dispensing Toolkit and response plan for initial 10-day post-exposure antibiotic prophylaxis was developed for use by a local health department in the event of a mass anthrax exposure at a US Post Office sorting facility. The pharmacist's role in medical countermeasures planning for anthrax exposure is also discussed to illustrate how pharmacists' medication expertise can be utilized. EVALUATION: The CDC's Public Health Preparedness Capabilities: National Standards for State and Local Planning framework and inputs from an interprofessional stakeholder team were used to develop a Medical Countermeasures Response Plan and Implementation Toolkit for mass point-of-dispensing (POD) in the event of an anthrax exposure. IMPLEMENTATION AND DISSEMINATION: Stakeholders attended a USPS Community Partner Training event where additional revisions to the toolkit were made. The toolkit and standing order are now implemented at the local health department to be reviewed and updated on a yearly basis by health department leadership. DISCUSSION: Pharmacists can use their medication expertise and experience with patient education to design emergency response plans focused on increasing patient safety and medication adherence. Pharmacists should be involved in emergency response and medical countermeasures planning that involve medications.

Teaching Brief Motivational Interventions for Diabetes to Family Medicine Residents.

BACKGROUND AND OBJECTIVES: As time and resource constraints grow in primary care, so does the value of efficient strategies to promote patient self-management, particularly for chronic diseases such as diabetes mellitus (DM). To that end, incorporating motivational interviewing (MI) into clinical practice has been shown to improve outcomes for patients with DM. Brief motivational interventions (BMI) draw from MI and may be integrated into more concise office visits. Little research has investigated strategies for BMI training for family medicine residents, particularly in the care of patients with DM. This study evaluates the impact of BMI training on improving DM self-management. METHODS: Family medicine residents were trained in BMI for DM over four sessions, then implemented BMI during routine office visits for 1 year. Pre- and post-implementation surveys were compared between residents who received BMI training and those who did not. RESULTS: After BMI training, residents' self-reported use of MI-adherent approaches to managing unhealthy behaviors in patients with DM doubled, and knowledge of MI increased by nearly 50%. BMI-trained residents showed 19% improvement in the application of MI skills, using an objective measure of open-response questions to behavioral change statements. CONCLUSIONS: After fewer than four training sessions in BMI, residents not only improved in their ability to apply motivational skills but also altered their clinical approaches to counseling patients with DM. BMI can also be used to evoke health behavior changes, thereby improving self-management. Training family medicine residents in BMI is effective and can be easily incorporated into a residency curriculum.

Helmsman is expressed in both trachea and photoreceptor development: partial inactivation alters tracheal morphology and visually guided behavior.

We have identified helmsman (hlm), which is expressed in the fruit fly photoreceptor cells during neural network development. Hlm is also expressed in the elongating cells of the embryonic trachea. Both photoreceptor neurons and embryonic trachea cells elongate in precise, targeted growth for cell-to-cell specific recognition. Expression of antisense hlm-interfering RNA during embryogenesis arrests elongation of the developing tracheal cells and blocks maturation. Expression of hlm-interfering RNA during visual system formation results in reduced visual acuity and poor performance in optomotor response, indicative of abnormal neural network development. Hlm is a unique cell surface protein with complement-like protein interaction motifs. We have also cloned hlm from Lucilia cuprina (Australian blowfly), which is approximately 100 million years divergent from Drosophila, and find a remarkable 90% protein identity over the entire 558 amino acid protein. Analysis of the hlm sequence found in other species indicates a significant evolutionary pressure to maintain the hlm protein sequence. Our interpretation is that hlm is involved in cell maturation in both the elongating trachea and elongating photoreceptor cells. Cell adhesion and cell signaling, which are known to use immunoglobulin-like cell adhesion molecules, may use molecular systems analogous to complement to create protein complexes to regulate growth.

Design and synthesis of noncompetitive metabotropic glutamate receptor subtype 5 antagonists.

A series of diaryl amides was designed and synthesized as novel nonethynyl mGluR5 antagonists. The systematic variation of the pharmacophoric groups led to the identification of a lead compound that demonstrated micromolar affinity for the mGluR5. Further optimization resulted in compounds with improved binding affinities and antagonist profiles, in vitro.

Structure-activity relationships of substituted N-benzyl piperidines in the GBR series: Synthesis of 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(2-trifluoromethylbenzyl)piperidine, an allosteric modulator of the serotonin transporter.

A series of 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-(substituted benzyl) piperidines with substituents at the ortho and meta positions in the aromatic ring of the N-benzyl side chain were synthesized and their affinities and selectivities for the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) were determined. One analogue, 4-(2-(bis(4-fluorophenyl)methoxy)ethyl)-1-(2-trifluoromethylbenzyl)piperidine (the C(2)-trifluoromethyl substituted compound), has been found to act as an allosteric modulator of hSERT binding and function. It had little affinity for any of the transporters. Several compounds showed affinity for the DAT in the low nanomolar range and displayed a broad range of SERT/DAT selectivity ratios and very little affinity for the NET. The pharmacological tools provided by the availability of compounds with varying transporter affinity and selectivity could be used to obtain additional information about the properties a compound should have to act as a useful pharmacotherapeutic agent for cocaine addiction and help unravel the pharmacological mechanisms relevant to stimulant abuse.

Studies of the biogenic amine transporters. XI. Identification of a 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR12909) analog that allosterically modulates the serotonin transporter.

Previous studies identified partial inhibitors of serotonin (5-HT) transporter and dopamine transporter binding. We report here on a partial inhibitor of 5-HT transporter (SERT) binding identified among a group of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine analogs (4-[2-[bis(4-fluorophenyl)-methoxy]ethyl]-1-(2-trifluoromethyl-benzyl)-piperidine; TB-1-099). Membranes were prepared from rat brains or human embryonic kidney cells expressing the cloned human dopamine (hDAT), serotonin (hSERT), and norepinephrine (hNET) transporters. beta-(4'-(125)Iodophenyl)tropan-2beta-carboxylic acid methyl ester ([(125)I]RTI-55) binding and other assays followed published procedures. Using rat brain membranes, TB-1-099 weakly inhibited DAT binding (K(i) = 439 nM), was inactive at NET binding ([(3)H]nisoxetine), and partially inhibited SERT binding with an extrapolated plateau ("A" value) of 20%. Similarly, TB-1-099 partially inhibited [(125)I]RTI-55 binding to hSERT with an extrapolated plateau (A value) of 14%. Upon examining the effect of increasing concentrations of TB-1-099 on the apparent K(d) and B(max) of [(125)I]RTI-55 binding to hSERT, we found that TB-1-099 decreased the B(max) in a dose-dependent manner and affected the apparent K(d) in a manner well described by a sigmoid dose-response curve. TB-1-099 increased the K(d) but not to the magnitude expected for a competitive inhibitor. In rat brain synaptosomes, TB-1-099 noncompetitively inhibited [(3)H]5-HT, but not [(3)H]dopamine, uptake. Dissociation experiments indicated that TB-1-099 promoted the rapid dissociation of a small component of [(125)I]RTI-55 binding to hSERT. Association experiments demonstrated that TB-1-099 slowed [(125)I]RTI-55 binding to hSERT in a manner unlike that of the competitive inhibitor indatraline. Viewed collectively, these results support the hypothesis that TB-1-099 allosterically modulates hSERT binding and function.