Pharmacy and Pharmaceutical Sciences Commons^™

Access To Essential Medicines In Pakistan: Policy And Health Systems Research Concerns., Shehla Zaidi, Maryam Bigdeli, Noureen Aleem, Arash Rashidian

Community Health Sciences

NTRODUCTION:

Inadequate access to essential medicines is a common issue within developing countries. Policy response is constrained, amongst other factors, by a dearth of in-depth country level evidence. We share here i) gaps related to access to essential medicine in Pakistan; and ii) prioritization of emerging policy and research concerns.

METHODS:

An exploratory research was carried out using a health systems perspective and applying the WHO Framework for Equitable Access to Essential Medicine. Methods involved key informant interviews with policy makers, providers, industry, NGOs, experts and development partners, review of published and grey literature, and consultative prioritization in stakeholder's Roundtable. …

In Vitro Characterization Of Avian Influenza Virus Isolates With A Truncated Ns1 Gene Segment, Aaron Dick

Honors Scholar Theses

Avian Influenza Virus represents a significant threat to the world poultry population, and is a potential threat to humans due to the possibility of cross-species AIV infection. Our approach is to characterize a number of avian virus populations with respect to their content of biologically active particles that include hemagglutinating particles (HAP), plaque forming particles (PFP), interferon inducing particles (IFP), interferon induction-suppressing particles (ISP), defective-interfering particles (DIP), cell-killing particles (CKP) and non-infectious cell killing particles (niCKP) using unique in vitro assays developed for avian influenza virus in the Marcus-Sekellick Laboratory. Specifically, we will use a strain of Avian influenza virus, …

A Series Of Pharmaceutical Technology Concepts Applied To Pediatric Formulations, Hao Lou

Theses and Dissertations (ETD)

Pediatric formulations have received great attention from regulatory agencies in the United States and Europe. Since solid dosage forms such as tablets and capsules will not be able to improve pediatric patients’ compliance, customized pediatric formulations are needed. In response, formulators in the pharmaceutical industry have made significant effort into developing various pediatric formulations. However, developing satisfactory pediatric formulations is a process that is guided by case by case basis. The objective of this current study was to apply the scientific pharmaceutical technology concepts into developing modern pediatric formulations. We have shown that the drug delivery design will be affected …

Role Of Ethanol As A Cofactor In Haart Induced Hepatic Steatosis And Injury., Hridgandh Donde

Electronic Theses and Dissertations

Highly Active Antiretroviral Therapy (HAART) has led to a significant increase in the life expectancy of HIV patients; however, there are significant side effects including lipodystrophy and hepatotoxicity. Alcohol abuse is highly prevalent in HIV infected individuals and hence may be a significant negative cofactor in HAART induced hepatotoxicity. The present study examines the mechanisms underlying HAART and alcohol induced hepatotoxicity. The effects of HAART drugs (azidothymidine, and Indinavir sulphate) in combination with alcohol were examined in in vivo animal model. Alcohol and HAART drug interactions and hepatotoxicity were also assessed in-vivo using an animal model of chronic alcohol feeding. …

Risk Factors For Postoperative Cognitive Dysfunction In Older Adults Undergoing Major Noncardiac Surgery, Osama Shoair

Theses and Dissertations

Background: Postoperative cognitive dysfunction (POCD) is a deterioration in cognitive function that occurs after surgery as measured by neuropsychological tests. The purpose of this study was to determine the incidence and risk factors for POCD in older adults three months after major noncardiac surgery. Methods: This is a prospective study of patients aged 65 years and older who underwent major noncardiac surgery. Patients’ cognitive function was assessed before and three months after surgery using a computerized neurocognitive battery. Blood samples were withdrawn from patients before surgery to identify patients with high level of C-reactive protein (CRP), and patients who had …

Liposomal Fasudil, A Rho-Kinase Inhibitor, For Prolonged Pulmonary Preferential Vasodilation In Pulmonary Arterial Hypertension, Vivek Gupta, Nilesh Gupta, Imam H. Shaik, Reza Mehvar, Ivan F. Mcmurty, Masahiko Osa, Eva Nozik-Grayck, Fakhrul Ahsan

Pharmacy Faculty Articles and Research

Current pharmacological interventions for pulmonary arterial hypertension (PAH) require continuous infusions, multiple inhalations, or oral administration of drugs that act on various pathways involved in the pathogenesis of PAH. However, invasive methods of administration, short duration of action, and lack of pulmonary selectivity result in noncompliance and poor patient outcomes. In this study, we tested the hypothesis that encapsulation of an investigational anti-PAH molecule fasudil (HA-1077), a Rho-kinase inhibitor, into liposomal vesicles results in prolonged vasodilation in distal pulmonary arterioles. Liposomes were prepared by hydration and extrusion method and fasudil was loaded by ammonium sulfate-induced transmembrane electrochemical gradient. Liposomes were …

Crizotinib: A Tyrosine Kinase Inhibitor, Graham Mclaren

Honors Theses

Crizotinib is a small molecule tyrosine kinase inhibitor that is currently being marketed by Pfizer under the trade name Xalkori^®. After its development in 2005, an appropriate target was discovered in 2007. By 2011 the FDA had approved crizotinib for use in patients with ALK+ non small cell lung cancer (NSCLC). ALK+ NSCLC is caused by a genetic mutation that truncates and flips a section of the EML4 gene and attaches it to a section of the ALK gene. The result is the EML4-ALK oncogene. The resulting protein from this mutation is capable of undergoing ligand independent dimerization, …

Understanding Molecular Interactions: Application Of Hint-Based Tools In The Structural Modeling Of Novel Anticancer And Antiviral Targets, And In Protein-Protein Docking, Hardik Parikh

Theses and Dissertations

Computationally driven drug design/discovery efforts generally rely on accurate assessment of the forces that guide the molecular recognition process. HINT (Hydropathic INTeraction) is a natural force field, derived from experimentally determined partition coefficients that quantifies all non-bonded interactions in the biological environment, including hydrogen bonding, electrostatic and hydrophobic interactions, and the energy of desolvation. The overall goal of this work is to apply the HINT-based atomic level description of molecular systems to biologically important proteins, to better understand their biochemistry – a key step in exploiting them for therapeutic purposes. This dissertation discusses the results of three diverse projects: i) …

Stemming The Global Trade In Falsified And Substandard Medicines, Lawrence O. Gostin, Gillian J. Buckley, Patrick W. Kelley

Georgetown Law Faculty Publications and Other Works

Drug safety and quality is an essential assumption of clinical medicine, but there is growing concern that this assumption is not always correct. Poor manufacturing and deliberate fraud occasionally compromises the drug supply in the United States, and the problem is far more common and serious in low- and middle-income countries with weak drug regulatory systems. An Institute of Medicine consensus committee report identified the causes and possible solutions to the problem of falsified and substandard drugs around the world.

The vocabulary people use to discuss the problem is itself a concern. The word counterfeit is often used innocuously to …

Glycosylate Derivatives Of Mithramycin, Method Of Preparation And Uses Thereof, Jürgen Rohr, Irfan Baig, Jose Antonio Salas Fernandez, Alfredo Fernandez Brana, Maria Perez Solares

Pharmaceutical Sciences Faculty Patents

The present invention provides compounds characterized by the formula (I), where each of the substituent radicals is described in the specification. The invention also describes the use of said compounds in the treatment of various diseases, including: cancer or tumoral processes in general, Paget's disease, hypercalcaemia, hypercalciuria and neurological diseases (inter alia, Parkinson's, Alzheimer's, Huntington's).

Design, Synthesis And Evaluation Of Antimicrobial Activity Of N-Terminal Modified Leucocin A Analogues, Krishna Chaitanya Bodapati, Rania Soudy, Hashem Etayash, Michael Stiles, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Class IIa bacteriocins are potent antimicrobial peptides produced by lactic acid bacteria to destroy competing microorganisms. The N-terminal domain of these peptides consists of a conserved YGNGV sequence and a disulphide bond. The YGNGV motif is essential for activity, whereas, the two cysteines involved in the disulphide bond can be replaced with hydrophobic residues. The C-terminal region has variable sequences, and folds into a conserved amphipathic α-helical structure. To elucidate the structure–activity relationship in the N-terminal domain of these peptides, three analogues (1–3) of a class IIa bacteriocin, Leucocin A (LeuA), were designed and synthesized by …

Acute Pharmacological Treatment Given To Older Adults With Acute Myocardial Infarction: A Nationwide Emergency Department Study, 1992-2010, Maryam S. Alowayesh

Theses and Dissertations

OBJECTIVES: To determine the pattern and predictors of use of antiplatelet agents and beta-blockers given in the emergency department (ED) to older adults with acute myocardial infarction (AMI) and its effects on in-hospital mortality and length of hospital stay (LOS) and to determine the effect of computerized ED guideline reminders on their utilization. METHODS: A cross-sectional study using the National Hospital Ambulatory Medical Care Survey (NHAMCS) ED data for years 1992 to 2010 was conducted. Patients were included if they had an admission diagnosis of AMI (ICD-9-CM code 410.xx) and were ≥55 years. Survey logistic regression was used to examine …

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 …

Pancreatic Angiotensin-Converting Enzyme 2 Improves Glycemia In Angiotensin Ii-Infused Mice, Kavaljit H. Chhabra, Huijing Xia, Kim Brint Pedersen, Robert C. Speth, Eric Lazartigues

HPD Articles

An overactive renin-angiotensin system (RAS) is known to contribute to type 2 diabetes mellitus (T2DM). Although ACE2 overexpression has been shown to be protective against the overactive RAS, a role for pancreatic ACE2, particularly in the islets of Langerhans, in regulating glycemia in response to elevated angiotensin II (Ang II) levels remains to be elucidated. This study examined the role of endogenous pancreatic ACE2 and the impact of elevated Ang II levels on the enzyme's ability to alleviate hyperglycemia in an Ang II infusion mouse model. Male C57bl/6J mice were infused with Ang II or saline for a period of …

Chemically Diverse Microtubule Stabilizing Agents Initiate Distinct Mitotic Defects And Dysregulated Expression Of Key Mitotic Kinases., Cristina C. Rohena, Jiangnan Peng, Tyler A. Johnson, Phillip Crews, Susan L. Mooberry

Natural Sciences and Mathematics | Faculty Scholarship

Microtubule stabilizers are some of the most successful drugs used in the treatment of adult solid tumors and yet the molecular events responsible for their antimitotic actions are not well defined. The mitotic events initiated by three structurally and biologically diverse microtubule stabilizers; taccalonolide AJ, laulimalide/fijianolide B and paclitaxel were studied. These microtubule stabilizers cause the formation of aberrant, but structurally distinct mitotic spindles leading to the hypothesis that they differentially affect mitotic signaling. Each microtubule stabilizer initiated different patterns of expression of key mitotic signaling proteins. Taccalonolide AJ causes centrosome separation and disjunction failure to a much greater extent …

Angiotensin Type 1 Receptor Resistance To Blockade In The Opossum Proximal Tubule Cell Due To Variations In The Binding Pocket, Ravi Nistala, Bradley T. Andresen, Lakshmi Pulakat, Alex Meuth, Catherine Sinak, Chirag Mandavia, Thomas Thekkumkara, Robert C. Speth, Adam Whaley-Connell, James R. Sowers

HPD Articles

Blockade of the angiotensin (ANG) II receptor type 1 (AT(1)R) with angiotensin receptor blockers (ARBs) is widely used in the treatment of hypertension. However, ARBs are variably effective in reducing blood pressure, likely due, in part, to polymorphisms in the ARB binding pocket of the AT(1)R. Therefore, we need a better understanding of variations/polymorphisms that alter binding of ARBs in heterogeneous patient populations. The opossum proximal tubule cell (OKP) line is commonly used in research to evaluate renal sodium handling and therefore blood pressure. Investigating this issue, we found natural sequence variations in the opossum AT(1)R paralleling those observed in …

Development Of Antagonists Targeting Chemokine Receptor Ccr5 And The Chemokine Receptor Ccr5 – Mu Opioid Receptor Heterodimer, Christopher Kent Arnatt

Theses and Dissertations

The chemokine receptor CCR5 (CCR5) plays an integral role within the inflammatory network of cells. Importantly, CCR5 is a mediator in several disease states and can be targeted using small molecule antagonists. Within this work, CCR5’s role in prostate cancer and HIV/AIDS has been exploited in order to develop potential therapeutics and probes. First, a series of novel compounds was designed by using pharmacophore-based drug design based upon known CCR5 antagonists and molecular modeling studies of the CCR5 receptor’s three-dimensional conformation. Once synthesized, these compounds were tested for their CCR5 antagonism and their anti-proliferative effects in several prostate cancer cell …

The Influence Of Faculty Mentors On Junior Pharmacy Faculty Members’ Career Decisions, Nicholas E. Hagemeier, Matthew M. Murawski, Nicholas G. Popovich

ETSU Faculty Works

Objective. To assess junior faculty members’ perceptions regarding the impact of past faculty-mentoring relationships in their career decisions, including the decision to pursue postgraduate training and ultimately an academic career.

Methods. A mixed-mode survey instrument was developed and an invitation to participate in the survey was sent to 2,634 pharmacy faculty members designated as assistant professors in the American Association of Colleges of Pharmacy (AACP) directory data.

Results. Usable responses were received from 1,059 pharmacy faculty members. Approximately 59% of respondents indicated that they had received encouragement from 1 or more faculty mentors that was very or extremely influential in …

Advocacy For Pneumonia Prevention In Korea: A Multi-Dimensional Program Organised Around World Pneumonia Day, Soon A. Kim, Paul E. Kilgore

Department of Pharmacy Practice

There are limited examples of population-based approaches that engage a broad range of stakeholders for prevention of pneumonia. In 2010, a multi-dimensional public-private partnership was established around World Pneumonia Day (WPD) in Seoul, Korea and included the following components: a) formation of an expert advisory group, b) creation of educational materials tailored for lay persons, c) creation of a dedicated WPD internet website in the local language, d) organisation of a WPD venue in central Seoul, e) creation of video and social networking messages for wide distribution, and f) engagement of parents, health-care professionals, public health agencies and policymakers. This …

In Vitro Anticancer Screening Of 24 Locally Used Nigerian Medicinal Plants, Saudat Adamson Fadeyi, Olugbeminiyi O. Fadeyi, Adedeji A. Adejumo, Cosmas Okoro, Elbert L. Myles

Chemistry Faculty Research

Background

Plants that are used as traditional medicine represent a relevant pool for selecting plant candidates that may have anticancer properties. In this study, the ethnomedicinal approach was used to select several medicinal plants native to Nigeria, on the basis of their local or traditional uses. The collected plants were then evaluated for cytoxicity.

Methods

The antitumor activity of methanolic extracts obtained from 24 of the selected plants, were evaluated in vitro on five human cancer cell lines.

Results

Results obtained from the plants screened indicate that 18 plant extracts of folk medicine exhibited promising cytotoxic activity against human carcinoma …