Pharmacy and Pharmaceutical Sciences Commons^™

Exploring The Effect Of Solution Speciation On Crystallization Outcome, David M. Harvey, Arjun Kalra, Tonglei Li

The Summer Undergraduate Research Fellowship (SURF) Symposium

In the field of pharmaceuticals, the crystallization process significantly impacts the purity, morphology and polymorphism of active pharmaceutical ingredients (API), all of which are important in drug development. Polymorphism is the existence of more than one solid-state form of the same chemical entity. Tolfenamic acid (TFA), a Non-Steroid Anti-inflammatory drug (NSAID), has been shown to exhibit a unique physical phenomenon called concomitant polymorphism, whereby two polymorphs crystallize from the solution simultaneously. From previous work, it has been established that solution speciation i.e. the presence of monomers or dimers of TFA in solution is concentration and temperature dependent. This study correlates …

Effect Of Twin Screw Granulator Process Parameters On Granule Attributes, Haosheng Xu, Ridade Sayin, James Litster

The Summer Undergraduate Research Fellowship (SURF) Symposium

Twin screw wet granulation has been considered as an efficient and effective technique of manufacturing granules (agglomerates made up of small particles) and has been widely applied in pharmaceutical industry. However, narrow granule size distributions are difficult to achieve. This study aims to elucidate the effect of process parameters such as liquid feed rate and screw configuration on the granule attributes through granule characterization. The methods used are sieve analysis (for size distribution), liquid distribution (determining the dye concentration in the granules) and density and porosity (percentage gas volume in the granule) analyses. A sieve shaker is used to divide …

Controlling Protein Release Using Biodegradable Microparticles, Benjamin Patrick Kline

Open Access Theses

Research in the field of protein therapeutics has exploded over the past decade and continues to grow in both academia and in industry. Protein drugs have advantages of being highly specific and highly active making them coveted targets for high profile disease states like cancer and multiple sclerosis. Unfortunately, their many advantages are complemented by their obstacles. Because proteins are highly active and highly specific, the window between efficacy and toxicity is very narrow and drug development can be long and arduous. In addition, protein activity is dependent on its specific folding conformation that is easily disrupted by a variety …

A Genome-Wide Association Study Identifies A Locus On Tert For Mean Telomere Length In Han Chinese., Yun Liu, Lan Cao, Zhiqiang Li, Daizhan Zhou, Wanqing Liu, Qin Shen, Yanting Wu, Dan Zhang, Xun Hu, Ting Wang, Junyi Ye, Xiaoling Weng, Hong Zhang, Di Zhang, Zhou Zhang, Fatao Liu, Lin He, Yongyong Shi

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Leukocyte telomere length (LTL) is a predictor of aging and a number of age-related diseases. We performed genome-wide association studies of mean LTL in 2632 individuals,with a two-stage replication in 3917 individuals from Chinese populations. To further validate our findings, we get the results of 696 samples from a cohort of European ancestry. We identified two loci associated with LTL that map in telomerase reverse transcriptase (TERT; rs2736100, P = 1.93×10−5) on chromosome 5p15.33 and near keratin 80 (KRT80; rs17653722, P = 6.96×10−6) on 12q13.13. In Chinese population each C allele of rs2736100 and T allele …

A Service Learning Experience For Pharmacy Students Involving Unwanted Medication Collection, Patricia L. Darbishire

IMPACT Symposium

This poster outlining a serve learning experience of students in Purdue’s pharmacy program was presented at the IMPACT Symposium 2014.

Structure Based Identification And Characterization Of Flavonoids That Disrupt Human Papillomavirus-16 E6 Function, Elliot J. Androphy, Jonathan J. Cherry, Anne Rietz, Anna Malinkevich, Yuqi Liu, Meng Xie, Matthew D. Bartolowits, Vincent J. Davisson, James D. Baleja

Department of Medicinal Chemistry and Molecular Pharmacology Graduate Student Publications

Expression and function of the human papillomavirus (HPV) early protein 6 (E6) is necessary for viral replication and oncogenesis in cervical cancers. HPV E6 targets the tumor suppressor protein p53 for degradation. To achieve this, “high-risk” HPV E6 proteins bind to and modify the target specificity of the ubiquitin ligase E6AP (E6 associated protein). This E6-dependent loss of p53 enables the virus to bypass host cell defenses and facilitates virally induced activation of the cell cycle progression during viral replication. Disruption of the interaction between E6 and E6AP and stabilization of p53 should decrease viability and proliferation of HPV positive …

Survey Of Pharmacist-Managed Primary Care Clinics Using Healthcare Failure Mode And Effect Analysis (Hfmea), Ashley H. Meredith, Jasmine Gonzalvo, Darin Ramsey, Alison M. Walton, Zachary Alan Weber, Jessica E. Wilhoite

Department of Pharmacy Practice Faculty Publications

Objectives: The primary objective was to expand upon results of a previously piloted patient perception survey with Healthcare Failure Mode and Effect Analysis (HFMEA), to identify areas within pharmacist-managed clinics needing improvement.

Methods: The survey was adapted for use in pharmacist-managed clinics. Patients completed the survey following regularly scheduled pharmacist appointments. Data were analyzed with a method adapted from HFMEA. Product scores could range from five to 25. A product of five indicates that pharmacists are doing a good job on the items that patients place the most value on, while a product score of 25 indicates that pharmacists are …

Investigating Intermolecular Interactions In Crystalline Aspirin Using Cdft, Nicholas Turner, Tonglei Li, Mingtao Zhang

The Summer Undergraduate Research Fellowship (SURF) Symposium

Drugs today are widely administered in their crystalline form, namely via tablets and capsules. The crystal structure of a drug molecule affects important drug qualities such as solubility, bioavailability, shelf life, and compaction properties. In order to form a basis for crystal structure prediction, it is necessary to first understand how intermolecular interactions cause molecules to pack in certain ways. Being able to predict and perhaps even control a drug molecule’s crystal structure will lead to the development of higher quality drugs that perform more consistently. Scientists and engineers do not fully understand the reasons for a molecule assuming a …

Investigation Of Major Intermolecular Interactions In 7,8-Dihydrobenzo(K)Phenanthridin-6(5h)-One Crystal Using Quantum Calculations And Crystallographic Visualization Programs, Zhiwei Liao, Tonglei Li, Mingtao Zhang

The Summer Undergraduate Research Fellowship (SURF) Symposium

Currently, tablets and capsules are the most common ways of delivering drugs. The active pharmaceutical ingredients and excipients used to make those tablets and capsules are in their crystalline form generally. However, a single molecule can form multiple different crystal structures because of different packing arrangements of the molecules. These different crystal structures have identical chemical composition but different properties such as solubility, density, stability, etc. This phenomenon is called polymorphism. Occurrence of polymorphism could be a disaster for both patients and pharmaceutical companies, as the drug could lose its efficacy due to changes in properties. Studying intermolecular interactions in …

Patient Perceptions Of Physicians And Medication Adherence Among Medicare Part D Beneficiaries, Lori Marquinne Ward

Open Access Dissertations

Ward, Lori Marquinne. Ph.D., Purdue University, December, 2013. Patient Perceptions of Physicians and Medication Adherence Among Medicare Part D Beneficiaries. Major Professor: Joseph Thomas III.

An observational database analysis using Medicare Current Beneficiary Survey data was conducted to examine patient perceptions of physicians and associations with adherence to antihypertensive medication among Medicare beneficiaries enrolled in Medicare Part D. The study sample included beneficiaries if they were 65 years or older, dwelling in the community, had a diagnosis of hypertension in 2007, were enrolled in Medicare Part D all 12 months in 2008, and had Medicare Part D claims for antihypertensive …

Patients' Perceptions Of Provider Communication, Provider Knowledge And Provider Competence And Associations With Potentially Inappropriate Medication Use Among Medicare Part D Beneficiaries, Engels Nnamdi Obi

Open Access Dissertations

The objectives for this study were to determine prevalence and incidence of potentially inappropriate medication (PIM) use among community-dwelling Medicare Part D beneficiaries, and to assess associations between patients' perceptions of provider communication, provider knowledge, and provider competence with PIM use. A retrospective observational analysis was conducted using data from the Medicare Current Beneficiary Survey. Individuals were included in the prevalence sample if they were aged 65 years or older in 2008, continuously enrolled in Medicare Part D from October 2007 through December 2008, and living in the community from October 2007 through December 2008. Individuals were included in the …

Health Care Resource Utilization And Expenditures In Persons With Autosomal Dominant Polycystic Kidney Disease, Neeraj Neelakantan Iyer

Open Access Dissertations

The objectives of this study were to determine prevalence of autosomal dominant polycystic kidney disease (ADPKD), to determine all-cause health care resource utilization and all-cause health care expenditures, to determine incremental health care resource utilization, and to determine incremental health care expenditures associated with ADPKD. An observational database analysis of a privately insured population was conducted using information from a large administrative claims database. Individuals 18 years of age or older and enrolled in a tracked health plan anytime during the period from April 1, 2011 through March 31, 2012, were eligible for inclusion in the sample for determination of …

Solvent Dependency Of The Uv-Vis Spectrum Of Indenoisoquinolines: Role Of Keto-Oxygens As Polarity Interaction Probes., Andrea Coletta, Silvia Castelli, Giovanni Chillemi, Nico Sanna, Mark S. Cushman, Yves Pommier, Alessandro Desideri

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Indenoisoquinolines are the most promising non-campthotecins topoisomerase IB inhibitors. We present an integrated experimental/computational investigation of the UV-Vis spectra of the IQNs parental compound (NSC314622) and two of its derivatives (NSC724998 and NSC725776) currently undergoing Phase I clinical trials. In all the three compounds a similar dependence of the relative absorption intensities at 270 nm and 290 nm on solvent polarity is found. The keto-oxygens in positions 5 and 11 of the molecular scaffold of the molecule are the principal chromophores involved in this dependence. Protic interactions on these sites are also found to give rise to absorptions at wavelengthsolution, …

Screening For Diabetes And Hypertension In A Rural Low Income Setting In Western Kenya Utilizing Home-Based And Community-Based Strategies, Sonak Pastakia, Shamim M. Ali, Jemima H. Kamano, Constantine O. Akwanalo, Samson K. Ndege, Victor L. Buckwalter, Rajesh Vedanthan, Gerald S. Bloomfield

Department of Pharmacy Practice Faculty Publications

BACKGROUND:

The burdens of hypertension and diabetes are increasing in low- and middle-income countries (LMICs). It is important to identify patients with these conditions early in the disease process. The goal of this study, therefore, is to compare community- versus home-based screening for hypertension and diabetes in Kenya.

METHODS:

This was a feasibility study conducted by the Academic Model Providing Access to Healthcare (AMPATH) program in Webuye, a town in western Kenya. Home-based (door-to-door) screening occurred in March 2010 and community-based screening in November 2011. HIV counselors were trained to screen for diabetes and hypertension in the home-based screening with …

Synthesis And Biological Evaluation Of Novel Folic Acid Receptor-Targeted, Β-Cyclodextrin-Based Drug Complexes For Cancer Treatment., Juan-Juan Yin, Sonali Sharma, Stepan P. Shumyak, Zhi-Xin Wang, Zhi-Wei Zhou, Yangde Zhang, Peixuan Guo, Chen-Zhong Li, Jagat R. Kanwar, Tianxin Yang, Shyam S. Mohapatra, Wanqing Liu, Wei Duan, Jian-Cheng Wang, Qi Li, Xueji Zhang, Jun Tan, Lee Jia, Jun Liang, Ming Q. Wei, Xiaotian Li, Shu-Feng Zhou

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Drug targeting is an active area of research and nano-scaled drug delivery systems hold tremendous potential for the treatment of neoplasms. In this study, a novel cyclodextrin (CD)-based nanoparticle drug delivery system has been assembled and characterized for the therapy of folate receptor-positive [FR(+)] cancer. Water-soluble folic acid (FA)-conjugated CD carriers (FACDs) were successfully synthesized and their structures were confirmed by 1D/2D nuclear magnetic resonance (NMR), matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS), high performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), and circular dichroism. Drug complexes of adamatane (Ada) and cytotoxic doxorubicin (Dox) with FACD were readily …

Epigenetic Regulation Of Bmp2 By 1,25-Dihydroxyvitamin D3 Through Dna Methylation And Histone Modification., Baisheng Fu, Hongwei Wang, Jinhua Wang, Ivana Barouhas, Wanqing Liu, Adam Shuboy, David A. Bushinsky, Dongsheng Zhou, Murray J. Favus

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Genetic hypercalciuric stone-forming (GHS) rats have increased intestinal Ca absorption, decreased renal tubule Ca reabsorption and low bone mass, all of which are mediated at least in part by elevated tissue levels of the vitamin D receptor (VDR). Both 1,25-dihydroxyvitamin D3(1,25(OH)2D3) and bone morphogenetic protein 2 (BMP2) are critical for normal maintenance of bone metabolism and bone formation, respectively. The complex nature of bone cell regulation suggests a potential interaction of these two important regulators in GHS rats. In the present study, BMP2 expression is suppressed by the VDR-1,25(OH)2D3 complex in Bone Marrow Stromal Cells (BMSCs) from GHS and SD …

Binding Of An Indenoisoquinoline To The Topoisomerase-Dna Complex Induces Reduction Of Linker Mobility And Strengthening Of Protein-Dna Interaction., Giordano Mancini, Ilda D'Annessa, Andrea Coletta, Giovanni Chillemi, Yves Pommier, Mark S. Cushman, Alessandro Desideri

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Long-duration comparative molecular dynamics simulations of the DNA-topoisomerase binary and DNA-topoisomerase-indenoisoquinoline ternary complexes have been carried out. The analyses demonstrated the role of the drug in conformationally stabilizing the protein-DNA interaction. In detail, the protein lips, clamping the DNA substrate, interact more tightly in the ternary complex than in the binary one. The drug also reduces the conformational space sampled by the protein linker domain through an increased interaction with the helix bundle proximal to the active site. A similar alteration of linker domain dynamics has been observed in a precedent work for topotecan but the molecular mechanisms were different …

Plk1 Phosphorylation Of Orc2 And Hbo1 Contributes To Gemcitabine Resistance In Pancreatic Cancer, Bing Song, X Shawn Liu, Steven J. Rice, Shihuan Kuang, Bennett D. Elzey, Stephen F. Konieczny, Timoty L. Ratliff, Tony R. Hazbun, Elena G. Chiorean, Xiaoqi Liu

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Although gemcitabine is the standard chemotherapeutic drug for treatment of pancreatic cancer, almost all patients eventually develop resistance to this agent. Previous studies identified Polo-like kinase 1 (Plk1) as the mediator of gemcitabine resistance, but the molecular mechanism remains unknown. In this study, we show that Plk1 phosphorylation of Orc2 and Hbo1 mediates the resistance to gemcitabine. We show that the level of Plk1 expression positively correlates with gemcitabine resistance, both in pancreatic cancer cells and xenograft tumors. Overexpression of Plk1 increases gemcitabine resistance, while inhibition of Plk1 sensitizes pancreatic cancer cells to gemcitabine treatment. To validate our findings, we …

Portable Bacterial Identification System Based On Elastic Light Scatter Patterns, Euiwon Bae, Dawei Ying, Donald Kramer, Valery Patsekin, Bartek Rajwa, Cheryl Holdman, Jennifer Sturgis, Vincent J. Davisson, J Paul Robinson

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Background

Conventional diagnosis and identification of bacteria requires shipment of samples to a laboratory for genetic and biochemical analysis. This process can take days and imposes significant delay to action in situations where timely intervention can save lives and reduce associated costs. To enable faster response to an outbreak, a low-cost, small-footprint, portable microbial-identification instrument using forward scatterometry has been developed.

Results

This device, weighing 9 lb and measuring 12 × 6 × 10.5 in., utilizes elastic light scatter (ELS) patterns to accurately capture bacterial colony characteristics and delivers the classification results via wireless access. The overall system consists of …

Bigpic: Bridging Income Generation With Provision Of Incentives For Care, Sonak Pastakia

Changing World Conference

No abstract provided.

Anti-Malarial Activity Of Geldanamycin Derivatives In Mice Infected With Plasmodium Yoelii, Rubul Mout, Zhi-Dong Xu, Angela Kh Wolf, Vincent J. Davisson, Gotam K. Jarori

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Background

Geldanamycin (GA), a benzoquinone ansamycin antibiotic has been shown in vitro to possess anti-plasmodial activity. Pharmacological activity of this drug is attributed to its ability to inhibit PfHSP90. The parasite growth arrest has been shown to be due to drug-induced blockage of the transition from ring to trophozoite stage. To further evaluate the consequences of this pharmacodyamic feature, the anti-malarial activity of GA analogs with enhanced drug properties in a Plasmodium-infected animal model have been evaluated for their capacity to induce clearance of the parasite. In the process, a hypothesis was subsequently tested regarding the susceptibility of the …

Improving Delirium Care In The Intensive Care Unit: The Design Of A Pragmatic Study, Noll L. Campbell, Babar A. Khan, Mark Farber, Tiffany Campbell, Anthony J. Perkins, Siu L. Hui, Greg Abernathy, John Buckley, Regg Sing, Jason Tricker, Mohammad Zawahiri, Malaz A. Boustani

Department of Pharmacy Practice Faculty Publications

Background

Delirium prevalence in the intensive care unit (ICU) is high. Numerous psychotropic agents are used to manage delirium in the ICU with limited data regarding their efficacy or harms.

Methods/Design

This is a randomized controlled trial of 428 patients aged 18 and older suffering from delirium and admitted to the ICU of Wishard Memorial Hospital in Indianapolis. Subjects assigned to the intervention group will receive a multicomponent pharmacological management protocol for delirium (PMD) and those assigned to the control group will receive no change in their usual ICU care. The primary outcomes of the trial are (1) delirium severity …

A Synergistic Antiproliferation Effect Of Curcumin And Docosahexaenoic Acid In Sk-Br-3 Breast Cancer Cells: Unique Signaling Not Explained By The Effects Of Either Compound Alone., Jeffrey D. Altenburg, Andrew A. Bieberich, Colin Terry, Kevin A. Harvey, Justin F. Vanhorn, Zhidong Xu, Vincent J. Davisson, Rafat A. Siddiqui

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Background

Breast cancer is a collection of diseases in which molecular phenotypes can act as both indicators and mediators of therapeutic strategy. Therefore, candidate therapeutics must be assessed in the context of multiple cell lines with known molecular phenotypes. Docosahexaenoic acid (DHA) and curcumin (CCM) are dietary compounds known to antagonize breast cancer cell proliferation. We report that these compounds in combination exert a variable antiproliferative effect across multiple breast cell lines, which is synergistic in SK-BR-3 cells and triggers cell signaling events not predicted by the activity of either compound alone.

Methods

Dose response curves for CCM and DHA …

Challenges Predicting Ligand-Receptor Interactions Of Promiscuous Proteins: The Nuclear Receptor Pxr., Sean Ekins, Sandhya Kortagere, Manisha Iyer, Erica J. Reschly, Markus A. Lill, Matthew R. Redinbo, Matthew D. Krasowski

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Transcriptional regulation of some genes involved in xenobiotic detoxification and apoptosis is performed via the human pregnane X receptor (PXR) which in turn is activated by structurally diverse agonists including steroid hormones. Activation of PXR has the potential to initiate adverse effects, altering drug pharmacokinetics or perturbing physiological processes. Reliable computational prediction of PXR agonists would be valuable for pharmaceutical and toxicological research. There has been limited success with structure-based modeling approaches to predict human PXR activators. Slightly better success has been achieved with ligand-based modeling methods including quantitative structure-activity relationship (QSAR) analysis, pharmacophore modeling and machine learning. In this …

A Protein Interaction Map Of The Mitotic Spindle, Jonathan Wong, Yuko Nakajima, Stefan Westermann, Ching Shang, Jung-Seog Kang, Crystal Goodner, Pantea Houshmand, Stanley Fields, Clarence S.M. Chan, David Drubin, Georjana Barnes, Tony R. Hazbun

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

The mitotic spindle consists of a complex network of proteins that segregates chromosomes in eukaryotes. To strengthen our understanding of the molecular composition, organization, and regulation of the mitotic spindle, we performed a system-wide two-hybrid screen on 94 proteins implicated in spindle function in Saccharomyces cerevisiae. We report 604 predominantly novel interactions that were detected in multiple screens, involving 303 distinct prey proteins. We uncovered a pattern of extensive interactions between spindle proteins reflecting the intricate organization of the spindle. Furthermore, we observed novel connections between kinetochore complexes and chromatin-modifying proteins and used phosphorylation site mutants of NDC80/TID3 to gain …

Riboflavin Synthase Of Schizosaccharomyces Pombe. Protein Dynamics Revealed By 19f Nmr Protein Perturbation Experiments., Markus Fischer, Ann-Kathrin Schott, Kristina Kemter, Richard Feicht, Gerald Richter, Boris Illarionov, Wolfgang Eisenreich, Stefan Gerhardt, Mark S. Cushman, Stefan Steinbacher, Robert Huber, Adelbert Bacher

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Background

Riboflavin synthase catalyzes the transformation of 6,7-dimethyl-8-ribityllumazine into riboflavin in the last step of the riboflavin biosynthetic pathway. Gram-negative bacteria and certain yeasts are unable to incorporate riboflavin from the environment and are therefore absolutely dependent on endogenous synthesis of the vitamin. Riboflavin synthase is therefore a potential target for the development of antiinfective drugs.

Results

A cDNA sequence from Schizosaccharomyces pombe comprising a hypothetical open reading frame with similarity to riboflavin synthase of Escherichia coli was expressed in a recombinant E. coli strain. The recombinant protein is a homotrimer of 23 kDa subunits as shown by sedimentation equilibrium …