Pharmacy and Pharmaceutical Sciences Commons^™

The Gating Charge Should Not Be Estimated By Fitting A Two-State Model To A Q-V Curve, Francisco Bezanilla, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

The voltage dependence of charges in voltage-sensitive proteins, typically displayed as charge versus voltage (Q-V) curves, is often quantified by fitting it to a simple two-state Boltzmann function. This procedure overlooks the fact that the fitted parameters, including the total charge, may be incorrect if the charge is moving in multiple steps. We present here the derivation of a general formulation for Q-V curves from multistate sequential models, including the case of infinite number of states. We demonstrate that the commonly used method to estimate the charge per molecule using a simple Boltzmann fit is not only inadequate, but in …

Minimizing Part D Costs For Medicare Beneficiaries: Not Just A Drop In The Bucket, Rajul A. Patel, Kate M. O'Dell, Kim-Anh Vo, Tiffany Chu, Kenneth Wang, Shu Lu, Joseph A. Woelfel, Sian M. Carr-Lopez, Suzanne M. Galal, Berit Gundersen

School of Pharmacy Faculty Presentations

Background: Although Medicare Part D has been largely successful in providing prescription drug coverage for Medicare beneficiaries, many continue to be burdened with unnecessary out-of-pocket (OOP) costs. Objective: This study sought to identify the frequency and impact of cost-lowering strategies used to assist Medicare beneficiaries with their Part D drug costs. Methods: Twelve outreach events were conducted in 6 different cities throughout Northern/Central California during the 2013 Medicare open enrollment period. During each event, trained student pharmacists under the supervision of licensed pharmacists assisted beneficiaries to minimize their OOP costs. Individualized assistance included: optimization of the beneficiary's Part D plan, …

Medicare Part D Prescription Drug Costs And Plan Satisfaction As A Function Of Student Pharmacists' Assistance, Rajul A. Patel, Kate M. O'Dell, Kenneth Wang, Shu Lu, Tiffany Chu, Kim-Anh Vo, Sian M. Carr-Lopez, Joseph A. Woelfel, Suzanne M. Galal, Berit Gundersen

School of Pharmacy Faculty Presentations

Background: Beneficiaries can become overwhelmed by the myriad of Medicare Part D (MPD) plans that offer prescription drug coverage. Poor choice and increased out-of-pocket (OOP) costs can be reduced through annual plan reevaluation. Objective: To examine beneficiaries' plan satisfaction and MPD drug costs as a function of prior assistance from trained student pharmacists. Methods: Twelve outreach events, nine at the same location as the previous year, were held throughout Northern/Central California during October-November 2012. Trained student pharmacists, at each event, identified the MPD plan best meeting a beneficiary's needs based on their current medications and personal preferences (e.g., preferred pharmacy). …

Sensing Charges Of The Ciona Intestinalis Voltage-Sensing Phosphatase, Carlos A. Villalba-Galea, Ludivine Frezza, Walter Sandtner, Francisco Bezanilla

School of Pharmacy Faculty Articles

Voltage control over enzymatic activity in voltage-sensitive phosphatases (VSPs) is conferred by a voltage-sensing domain (VSD) located in the N terminus. These VSDs are constituted by four putative transmembrane segments (S1 to S4) resembling those found in voltage-gated ion channels. The putative fourth segment (S4) of the VSD contains positive residues that likely function as voltage-sensing elements. To study in detail how these residues sense the plasma membrane potential, we have focused on five arginines in the S4 segment of the Ciona intestinalis VSP (Ci-VSP). After implementing a histidine scan, here we show that four arginine-to-histidine mutants, namely R223H to …

Medicare Part D Roulette: Potential Implications Of Random Assignment And Plan Restrictions, Rajul A. Patel, Mark P. Walberg, Joseph A. Woelfel, Michelle M. Amaral, Paresh Varu

School of Pharmacy Faculty Articles

Background: Dual-eligible (Medicare/Medicaid) beneficiaries are randomly assigned to a benchmark plan, which provides prescription drug coverage under the Part D benefit without consideration of their prescription drug profile. To date, the potential for beneficiary assignment to a plan with poor formulary coverage has been minimally studied and the resultant financial impact to beneficiaries unknown.

Objective: We sought to determine cost variability and drug use restrictions under each available 2010 California benchmark plan.

Methods: Dual-eligible beneficiaries were provided Part D plan assistance during the 2010 annual election period. The Medicare Web site was used to determine benchmark plan costs and prescription …

Turning Stealth Liposomes Into Cationic Liposomes For Anticancer Drug Delivery, Vijay Gyanani

University of the Pacific Theses and Dissertations

Targeting the anticancer agents selectively to cancer cells is desirable to improve the efficacy and to reduce the side effects of anticancer therapy. Previously reported passive tumor targeting by PEGylated liposomes (stealth liposomes) have resulted in their higher tumor accumulation. However their interaction with cancer cells has been minimal due to the steric hindrance of the PEG coating. This dissertation reports two approaches to enhance the interaction of stealth liposomes with cancer cells. First, we designed a lipid-hydrazone-PEG conjugate that removes the PEG coating at acidic pH as in the tumor interstitium. However, such a conjugate was highly unstable on …

Molecular Mechanism For Depolarization-Induced Modulation Of Kv Channel Closure, Alain J. Labro, Jerome J. Lacroix, Carlos A. Villalba-Galea, Dirk J. Snyders, Francisco Bezanilla

School of Pharmacy Faculty Articles

Voltage-dependent potassium (Kv) channels provide the repolarizing power that shapes the action potential duration and helps control the firing frequency of neurons. The K(+) permeation through the channel pore is controlled by an intracellularly located bundle-crossing (BC) gate that communicates with the voltage-sensing domains (VSDs). During prolonged membrane depolarizations, most Kv channels display C-type inactivation that halts K(+) conduction through constriction of the K(+) selectivity filter. Besides triggering C-type inactivation, we show that in Shaker and Kv1.2 channels (expressed in Xenopus laevis oocytes), prolonged membrane depolarizations also slow down the kinetics of VSD deactivation and BC gate closure during the …

A Human Phospholipid Phosphatase Activated By A Transmembrane Control Module, Christian R. Halaszovich, Michael G. Leitner, Angeliki Mavrantoni, Audrey Le, Ludivine Frezza, Anja Feuer, Daniela N. Schreiber, Carlos A. Villalba-Galea, Dominik Oliver

School of Pharmacy Faculty Articles

In voltage-sensitive phosphatases (VSPs), a transmembrane voltage sensor domain (VSD) controls an intracellular phosphoinositide phosphatase domain, thereby enabling immediate initiation of intracellular signals by membrane depolarization. The existence of such a mechanism in mammals has remained elusive, despite the presence of VSP-homologous proteins in mammalian cells, in particular in sperm precursor cells. Here we demonstrate activation of a human VSP (hVSP1/TPIP) by an intramolecular switch. By engineering a chimeric hVSP1 with enhanced plasma membrane targeting containing the VSD of a prototypic invertebrate VSP, we show that hVSP1 is a phosphoinositide-5-phosphatase whose predominant substrate is PI(4,5)P(2). In the chimera, enzymatic activity …

Medicare Part D Plan Optimization: The Need For An Annual Check-Up, Rajul A. Patel, Mark P. Walberg, Nataliya Mcelroy, Anil Mallya, Aesun Kim, Yvonne Mai, Justin Seo, Joseph A. Woelfel, Sian M. Carr-Lopez, Suzanne M. Galal

School of Pharmacy Faculty Presentations

Background: Since its inception, Medicare Part D requires beneficiaries to choose from a myriad of insurance plans in order to receive prescription drug coverage. Moreover, each year beneficiaries are confronted with plan cancellations, new plan offerings, changes in existing plan formularies and cost-sharing structure. Objective: This study prospectively examined the relationship between stand-alone prescription drug plan (PDP) costs, subsidy status, and the number of plans offered in California from 2009-2012. Methods: Forty-one community outreach events were held throughout Central/Northern California during the Medicare Part D annual election periods from 2008-2011. In total, 1,578 beneficiaries were assisted, 983 (62.2%) of whom …

Voltage-Controlled Enzymes: The New Janus Bifrons, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

The Ciona intestinalis voltage-sensitive phosphatase, Ci-VSP, was the first Voltage-controlled Enzyme (VEnz) proven to be under direct command of the membrane potential. The discovery of Ci-VSP conjugated voltage sensitivity and enzymatic activity in a single protein. These two facets of Ci-VSP activity have provided a unique model for studying how membrane potential is sensed by proteins and a novel mechanism for control of enzymatic activity. These facets make Ci-VSP a fascinating and versatile enzyme. Ci-VSP has a voltage sensing domain (VSD) that resembles those found in voltage-gated channels (VGC). The VSD resides in the N-terminus and is formed by four …

Impact Of An Elective Course On Pharmacy Students’ Attitudes, Beliefs, And Competency Regarding Medicare Part D, Suzanne M. Galal, Rajul A. Patel, Huong K. Thai, Christine M. Phou, Mark P. Walberg, Joseph A. Woelfel, Sian M. Carr-Lopez, Emily K. Chan

School of Pharmacy Faculty Articles

Objective. To determine the impact of an elective course on pharmacy students’ perceptions, knowledge, and confidence regarding Medicare Part D, medication therapy management (MTM), and immunizations.

Design. Thirty-three pharmacy students were enrolled in a Medicare Part D elective course that included both classroom instruction and experiential training.

Assessment. Students’ self-reported confidence in and knowledge of Part D significantly improved upon course completion. End-of-course student perceptions about the relative importance of various aspects of MTM interventions and their confidence in performing MTM services significantly improved from those at the beginning of the course. Students’ confidence in performing immunizations also increased significantly …

Controlling The Activity Of A Phosphatase And Tensin Homolog (Pten) By Membrane Potential, Jérôme J. Lacroix, Christian R. Halaszovich, Daniela N. Schreiber, Michael G. Leitner, Francisco Bezanilla, Dominik Oliver, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

The recently discovered voltage-sensitive phosphatases (VSPs) hydrolyze phosphoinositides upon depolarization of the membrane potential, thus representing a novel principle for the transduction of electrical activity into biochemical signals. Here, we demonstrate the possibility to confer voltage sensitivity to cytosolic enzymes. By fusing the tumor suppressor PTEN to the voltage sensor of the prototypic VSP from Ciona intestinalis, Ci-VSP, we generated chimeric proteins that are voltage-sensitive and display PTEN-like enzymatic activity in a strictly depolarization-dependent manner in vivo. Functional coupling of the exogenous enzymatic activity to the voltage sensor is mediated by a phospholipid-binding motif at the interface between voltage sensor …

Geriatric Care As An Introductory Pharmacy Practice Experience, Joseph A. Woelfel, Eric Boyce, Rajul A. Patel

School of Pharmacy Faculty Articles

Objective. To describe the design, delivery, and impact of a geriatric introductory pharmacy practice experience (IPPE) to develop students’ skills related to consultant pharmacists’ roles and patient care responsibilities.

Design. A required 2-unit geriatric IPPE, involving 40 hours in a geriatric-care facility, 5 reflection hours, and 12 classroom-discussion hours, was developed for first- and second-year pharmacy students. Students interviewed patients and caregivers, reviewed patient charts, triaged patient needs, prepared care plans, and performed quality-assurance functions.

Assessment. After completing the IPPE, students’ geriatric- and patient-care abilities were enhanced, based on review of their interactions, care plans, reflections, and examinations, and they …

Coupling Between The Voltage-Sensing And Phosphatase Domains Of Ci-Vsp, Carlos A. Villalba-Galea, Francesco Miceli, Maurizio Taglialatela, Francisco Bezanilla

School of Pharmacy Faculty Articles

The Ciona intestinalis voltage sensor-containing phosphatase (Ci-VSP) shares high homology with the phosphatidylinositol phosphatase enzyme known as PTEN (phosphatase and tensin homologue deleted on chromosome 10). We have taken advantage of the similarity between these proteins to inquire about the coupling between the voltage sensing and the phosphatase domains in Ci-VSP. Recently, it was shown that four basic residues (R11, K13, R14, and R15) in PTEN are critical for its binding onto the membrane, required for its catalytic activity. Ci-VSP has three of the basic residues of PTEN. Here, we show that when R253 and R254 (which are the homologues …

Tablet Splitting: To Split Or Not To Split, J. Obenrader, Joseph A. Woelfel

School of Pharmacy Faculty Articles

No abstract provided.

Medications That Should Not Be Crushed, K. Shaver, Joseph A. Woelfel

School of Pharmacy Faculty Articles

No abstract provided.

Comparison Of Chronic Wound Care Products, S. Hester, Joseph A. Woelfel

School of Pharmacy Faculty Articles

No abstract provided.

Medication Errors And Patient Safety Resources, Joseph A. Woelfel, W. Tom

School of Pharmacy Faculty Articles

No abstract provided.

Medications For Constipation, J. Allen, Joseph A. Woelfel

School of Pharmacy Faculty Articles

No abstract provided.

Optimization Of Porcine Buccal Mucosa For In Vitro Evaluation, Upendra D. Kulkarni

University of the Pacific Theses and Dissertations

Porcine buccal mucosa has been extensively used as in vitro model to study the permeability of drugs and assess their potential to deliver through buccal route. Porcine buccal mucosa is found to be very similar to human oral mucosa in structure and function. However, the in vitro permeation studies across porcine buccal mucosa show high variability which is mostly due to the various experimental and biological variables that are often overlooked while conducting such studies.

The precise nature of the permeability barrier offered by the various tissue layers of buccal mucosa was investigated in this study. It was observed that …

Drug Products With Medication Guides, Joseph A. Woelfel

School of Pharmacy Faculty Articles

No abstract provided.

Products With "Black Box" Warnings, Joseph A. Woelfel

School of Pharmacy Faculty Articles

No abstract provided.

Medications That Should Not Be Crushed, K. Shaver, Joseph A. Woelfel

School of Pharmacy Faculty Articles

No abstract provided.

Over-The-Counter Supplements For Cholesterol Lowering, K. M. Shields, Joseph A. Woelfel

School of Pharmacy Faculty Articles

No abstract provided.

Topical Treatment Of Chronic Wounds, Joseph A. Woelfel

School of Pharmacy Faculty Articles

No abstract provided.

Family Health Portrait, Joseph A. Woelfel

School of Pharmacy Faculty Articles

No abstract provided.

A Stepwise Guide To Selecting A Medicare Prescription Drug Plan, Joseph A. Woelfel

School of Pharmacy Faculty Articles

No abstract provided.

Medicare Part D Resources For The Health Professional, Joseph A. Woelfel

School of Pharmacy Faculty Articles

No abstract provided.

New Take-Home Screening Tests For Colon Cancer, Joseph A. Woelfel

School of Pharmacy Faculty Articles

No abstract provided.

Hipaa Confusion And Fear About Protected Health Information, Joseph A. Woelfel

School of Pharmacy Faculty Articles

No abstract provided.