Leading Change in Academic Pharmacy: Report of the 2018-2019 AACP Academic Affairs Committee.

The Committee was charged with the responsibility for examining the need for change in pharmacy education and the models of leadership that would enable that change to occur across the academy. They also examined the question of faculty wellbeing in a time of change and made several recommendations and suggestions regarding both charges. Building upon the work of the previous Academic Affairs Committee, the 2018-19 AAC encourages the academy to implement new curricular models supporting personalized learning that creates engaged and lifelong learners.

Consideration of Aggressive and Strategic Approaches to Address Declining Enrollment in US Pharmacy Schools.

Members from Cohort 13 of the Academic Leadership Fellows Program (ALFP) 2016-2017 were challenged to present a debate on the topic: "In Turbulent Times, Pharmacy Education Leaders Must Take Aggressive Action to Prevent Further Declines in Enrollment" at the American Association of Colleges of Pharmacy INfluence 2017 meeting in Rio Grande, Puerto Rico. This paper is the result of thoughtful insights emerging from this debate. We present a discussion of the question of whether pharmacy education leaders must take aggressive action or strategic approaches to prevent further declines in enrollment.

In vivo measurement of blood-brain barrier permeability.

This unit describes various protocols for the in vivo quantitation of drug permeability across the rodent blood - brain barrier. Methods for the measurement of drug influx or efflux are described, and support protocols are provided for determining intravascular capillary volume and cerebral perfusion flow. An in situ perfusion technique is also provided for assessing whether transport of a test compound occurs by carrier-mediated or saturable transport.

An interactive lesson in acid/base and pro-drug chemistry using sodium gamma-hydroxybutyrate and commercial test coasters.

Objective: To develop a classroom activity that applied pertinent pharmaceutical concepts to examine the use and limitations of a commercially available test drink coaster in detecting the presence of a date-rape drug, sodium gamma-hydroxybutyrate (NaGHB), in beverages.

Design: An activity exercise involving a combination of self-study, hands on participation, and classroom discussion was developed. Topics incorporated into the activity were drug-assisted rape, the concepts of false positives and negatives, and prodrug and pH chemistry.

Pharmacokinetics and pharmacodynamics of gamma-hydroxybutyric acid during tolerance in rats: effects on extracellular dopamine.

gamma-Hydroxybutyrate (GHB) is a potent sedative/hypnotic and drug of abuse. Tolerance develops to GHB's sedative/hypnotic effects. It is hypothesized that GHB tolerance may be mediated by alterations in central nervous system pharmacokinetics or neurotransmitter response.

Feasibility of D-glucuronate to enhance gamma-hydroxybutyric acid metabolism during gamma-hydroxybutyric acid toxicity: pharmacokinetic and pharmacodynamic studies.

Gamma-Hydroxybutyric acid (GHB) is a drug of abuse. Literature studies showed that D-glucuronate acts as an oxidative stimulator of GHB metabolism following in vivo GHB tracer doses. The present proof-of-concept study investigates if D-glucuronate enhances GHB metabolism and inhibits blood-brain barrier (BBB) carrier-mediated transport of GHB for clinically relevant and toxicological concentrations of GHB.

Alterations in neuronal transport but not blood-brain barrier transport are observed during gamma-hydroxybutyrate (GHB) sedative/hypnotic tolerance.

Purpose: To investigate if gamma-Hydroxybutyrate (GHB) tolerance is mediated by alterations in GHB systemic pharmacokinetics, transport (blood brain barrier (BBB) and neuronal) or membrane fluidity.

Materials And Methods: GHB tolerance in rats was attained by repeated GHB administration (5.31 mmol/kg, s.

Potential gamma-hydroxybutyric acid (GHB) drug interactions through blood-brain barrier transport inhibition: a pharmacokinetic simulation-based evaluation.

Recreational abuse or overdose of gamma-hydroxybutyric acid (GHB) results in dose-dependent central nervous system (CNS) effects including death. As GHB undergoes monocarboxylic acid transporter (MCT)-mediated transport across the blood-brain barrier (BBB), one possible strategy for the management of GHB toxicity/overdose involves inhibition of GHB BBB transport. To test this strategy, interactions between GHB and MCT substrates (salicylic acid or probenecid) were simulated.

GHB (gamma-hydroxybutyrate) carrier-mediated transport across the blood-brain barrier.

gamma-Hydroxybutyrate (sodium oxybate, GHB) is an approved therapeutic agent for cataplexy with narcolepsy. GHB is widely abused as an anabolic agent, euphoriant, and date rape drug. Recreational abuse or overdose of GHB (or its precursors gamma-butyrolactone or 1,4-butanediol) results in dose-dependent central nervous system (CNS) effects (respiratory depression, unconsciousness, coma, and death) as well as tolerance and withdrawal.

Nitric oxide neurotoxicity in neurodegenerative diseases.

Nitric oxide (nitrogen monoxide; NO) is a simple molecule with diverse biological functions. NO and related reactive nitrogen oxide species (RNOS) mediate intricate physiological and pathophysiological effects in the central nervous system. Depending on environmental conditions, NO and RNOS can initiate and mediate neuroprotection or neurotoxicity either exclusively or synergistically with other effectors.

In vitro studies indicate that miquelianin (quercetin 3-O-beta-D-glucuronopyranoside) is able to reach the CNS from the small intestine.

Miquelianin (quercetin 3-O-beta-D-glucuronopyranoside) is one of the flavonoids of St. John's wort (Hypericum perforatum L.) whose antidepressant activity has been shown by the forced swimming test, an in vivo pharmacological model with rats.

New and known iridoid- and phenylethanoid glycosides from Harpagophytum procumbens and their in vitro inhibition of human leukocyte elastase.

Ten compounds, harpagoside (1), 8- p-coumaroylharpagide (2), 8-feruloylharpagide (3), 8-cinnamoylmyoporoside (4), pagoside (5), acteoside (6), isoacteoside (7), 6'- O-acetylacteoside (8), cinnamic acid (9) and caffeic acid (10) were isolated from the storage roots of Harpagophytum procumbens, Pedaliaceae. Compounds 1, 2, 6, 7 and 9 are known for H. procumbens; 3 and 10 were isolated the first time from H.

Neuroinflammatory role of prostaglandins during experimental meningitis: evidence suggestive of an in vivo relationship between nitric oxide and prostaglandins.

Nitric oxide (NO) and prostaglandins are inflammatory mediators produced during meningitis. The purpose of the present study was to pharmacologically inhibit cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) to 1) explore the prostaglandin contribution to blood-cerebrospinal fluid barrier permeability alterations and 2) elucidate the in vivo concentration relationship between prostaglandin E2 (PGE2) and NO during experimental meningitis. Intracisternal injection of lipopolysaccharides (LPSs, 200 microg) induced neuroinflammation.

In vivo measurement of blood-brain barrier permeability.

This unit describes various protocols for the in vivo quantitation of drug permeability across the rodent blood-brain barrier. Methods for the measurement of drug influx and efflux are described, and support protocols are provided for determining intravascular capillary volume and cerebral perfusion flow. An in situ perfusion technique is also provided for assessing whether transport of a test compound occurs by carrier-mediated or saturable transport.

A critical evaluation of the brain efflux index method as applied to the nitric oxide synthase inhibitor, aminoguanidine.

The Brain Efflux Index (BEI) method is an in vivo procedure designed to quantitate saturable efflux mechanisms resident at the blood--brain barrier (BBB). The present work utilized the BEI method to assess the BBB efflux mechanisms of [(14)C]aminoguanidine, a nitric oxide synthase inhibitor. The BEI for [(14)C]aminoguanidine was >100% (relative to [(3)H]inulin diffusion) over a range of 41-184 pmol after 40 min.

Theoretical pharmacokinetic and pharmacodynamic simulations of drug delivery mediated by blood--brain barrier transporters.

Pharmacokinetic/pharmacodynamic simulations were performed to assess the feasibility of central nervous system (CNS) drug delivery via endogenous transporters resident at the blood-brain barrier (BBB). Pharmacokinetic models were derived for intravenous bolus dosing of a hypothetical drug in the absence or presence of an endogenous, competing transport inhibitor. These models were linked to CNS pharmacodynamic models where the effect sites were either cell surface receptors or intracellularly localized enzymes.

Blood-brain barrier transport studies of organic guanidino cations using an in situ brain perfusion technique.

Blood-brain barrier (BBB) transport of essential polar substrates is mediated by specific, carrier-mediated transport proteins. The BBB transport mechanisms for polar compounds with terminal guanidino functional groups (R-NHC(NH)NH(2)) are not well defined. The goal of the present work was to investigate the BBB transport mechanism(s) for terminal guanidino substrates using an in situ brain perfusion technique.

Nitric oxide redox species exert differential permeability effects on the blood-brain barrier.

Excessive production of nitric oxide (NO) in the central nervous system is suspected to contribute to neurodegenerative diseases. Previous studies showed that excessive central nervous system NO increased the permeability of the blood-brain barrier (BBB) during experimental meningitis. The present work hypothesizes that the various NO redox forms (NO(*), NO(+), NO(-)) differentially mediate disruption of the BBB.

Cellular transport processes of aminoguanidine, a nitric oxide synthase inhibitor, in the opossum kidney cell culture line.

Aminoguanidine has potential pharmacologic utility for diabetes and nitric oxide - mediated inflammation. Because aminoguanidine is positively charged at physiologic pH (pK(a) approximately 10), it is unlikely that simple diffusion is a predominant mechanism for cellular penetration. This study sought to determine the transport processes by which aminoguanidine, a cationic compound, traverses across cellular membranes.

Quantification of iNOS mRNA with reverse transcription polymerase chain reaction directly from cell lysates.

Inducible nitric oxide synthase (iNOS) is a member of a family of primary inflammatory response genes. Quantitative measurement of iNOS mRNA levels is important for the study of gene expression of this enzyme during the process of inflammation. We report here a method for quantitative measurement of iNOS mRNA levels with rtPCR directly from cells lysed with a single step phenol/chloroform/ether extraction.

Improved high-performance liquid chromatographic assay for nimesulide.

An improved, validated HPLC assay was developed for the non-steroidal anti-inflammatory agent, nimesulide. In contrast to previous methods, the present assay requires smaller plasma volumes (0.2 ml) and utilizes a commercially available, structurally similar analogue of nimesulide, NS-398.

Nitric oxide and prostaglandin E2 formation parallels blood-brain barrier disruption in an experimental rat model of bacterial meningitis.

During meningitis, the host produces a plethora of signaling agents as part of a coordinated defense mechanism against invading pathogens. Nitric oxide (NO) and prostaglandin E2 (PGE2) are two such inflammatory mediators produced in response to bacterial endotoxins. Disruption of the blood-brain barrier (BBB) is one of many pathophysiological consequences of meningitis.

Chronic dosing with 1-aminocyclopropanecarboxylic acid, a glycine partial agonist, modulates NMDA inhibition of muscarinic-coupled PI hydrolysis in rat cortical slices.

Chronic dosing with the glycine partial NMDA agonist, 1-aminocyclopropanecarboxylic acid (ACPC) elicited an altered allosteric regulation of cortical NMDA receptor binding. The present study hypothesized that these allosteric receptor binding changes would be manifest as pharmacologically functional reductions in NMDA receptor activity following chronic ACPC dosing. NMDA inhibition of carbachol-induced phosphoinositide (PI) hydrolysis was used as a functional assay to assess NMDA receptor function in rat cerebral cortex.

Chronic administration of NMDA glycine partial agonists induces tolerance in the Porsolt swim test.

The Porsolt swim test (PST) was used to assess behavioral effects following acute or chronic treatment with two N-methyl-D-aspartate (NMDA) glycine partial agonists, 1-aminocyclopropanecarboxylic acid (ACPC), and D-cycloserine (DCS). Consistent with previous findings in mice, single intravenous doses of ACPC in rats produced a significant, dose-dependent reduction in immobility in the PST compared to saline. Single dose DCS also elicited significant dose-dependent reductions in PST immobility times.

Inhibition of nitric oxide synthase attenuates blood-brain barrier disruption during experimental meningitis.

Increased permeability of the blood-brain (B-B) barrier is observed during meningitis. Preventing B-B barrier alterations is important because adverse neurological outcomes are correlated with breeches in barrier integrity. It was hypothesized that pathological production of nitric oxide (NO) contributes to B-B barrier disruption during meningitis in the rat.