Pharmaceutics and Drug Design Commons^™

Elaboration And Design Of Α7 Nachr Negative Allosteric Modulators, Osama I. Alwassil

Theses and Dissertations

α7 Neuronal nicotinic acetylcholine receptors are one of two major classes of receptors responsible for cholinergic neurotransmission in the central nervous system. The existence of α7 neuronal nAChRs in different regions of the nervous system suggests their involvement in certain essential physiological functions as well as in disorders such as Alzheimer’s disease (AD), drug dependence, and depression. This project was aimed toward the discovery and development of small–molecule arylguanidines that modulate α7 nAChR function with improved subtype-selectivity through an allosteric approach. Identifying the required structural features of these small molecules allowed optimization of their negative allosteric modulator (NAM) actions at …

Kinetics And Mechanisms Of Crystal Growth Inhibition Of Indomethacin By Model Precipitation Inhibitors, Dhaval D. Patel

Theses and Dissertations--Pharmacy

Supersaturating Drug Delivery Systems (SDDS) could enhance oral bioavailability of poorly water soluble drugs (PWSD). Precipitation inhibitors (PIs) in SDDS could maintain supersaturation by inhibiting nucleation, crystal growth, or both. The mechanisms by which these effects are realized are generally unknown. The goal of this dissertation was to explore the mechanisms underpinning the effects of model PIs including hydroxypropyl β-cyclodextrins (HP-β-CD), hydroxypropyl methylcellulose (HPMC), and polyvinylpyrrolidone (PVP) on the crystal growth of indomethacin, a model PWSD. At high degrees of supersaturation (S), the crystal growth kinetics of indomethacin was bulk diffusion-controlled, which was attributed to a high energy form deposited …

In Planta Production Of Flock House Virus Transencapsidated Rna And Its Potential Use As A Vaccine, Yiyang Zhou, Payal D. Maharaj, Jyothi K. Mallajosyula, Alison A. Mccormick, Christopher M. Kearney

Faculty Publications & Research of the TUC College of Pharmacy

We have developed a transencapsidated vaccine delivery system based on the insect virus, Flock House virus (FHV). FHV is attractive due to its small genome size, simple organization, and non-pathogenic characteristics. With the insertion of a Tobacco mosaic virus (TMV) origin of assembly (Oa), the independently replicating FHV RNA1 can be transencapsidated by TMV coat protein. In this study we demonstrated that the Oa adapted FHV RNA1 transencapsidation process can take place in planta, by using a bipartite plant expression vector system, where TMV coat protein is expressed by another plant virus vector, Foxtail mosaic virus (FoMV). Dual infection in …

The Slc22 Transporter Family: Novel Insights To Roles In Drug Efficacy, Drug-Drug Interactions And Mood Disorders, Xiaolei Pan

Theses and Dissertations

Numerous studies have demonstrated the impact of organic cation (OCTs; SLC22 family) and anion transporters (OATs; SLC22 family) on the efficacy and safety of clinically important therapeutics. To be specific, OCTs and OATs have been identified as determinants for uptake into and secretion from enterocytes, hepatocytes and renal proximal tubular cells, and are frequent sites of drug-drug interaction (DDI). In addition, OCTs expressed in brain are components of the low-affinity, high capacity clearance pathway (uptake-2) for biogenic monoamine neurotransmitters. As a result, OCTs may represent novel targets for mood disorders.

The inhibitory effects of several therapeutic agents, designed drugs and …

Analysis Of Humira, Electro-Acupuncture, And Pulsatile Dry Cupping On Reducing Joint Inflammation In Patients With Rheumatoid Arthritis, Natalie Noll

Auctus: The Journal of Undergraduate Research and Creative Scholarship

Humira, an anti-TNF drug aimed at decreasing inflammation in Rheumatoid Arthritis patients, can cause skin diseases from rashes to skin cancer. Humira works by blocking the chemical receptor RANKL which inhibits the production of osteoclasts. Osteoclasts are cells that attack and eat bone and cartilage therefore an inhibitory mechanism would cause inflammation.. By analyzing Humira’s effect on the human body, Humira can be compared to other treatments such as electro-acupuncture and pulsatile dry cupping to determine the viability of these alternative treatment methods in regards to their abilities to decrease inflammation in Rheumatoid Arthritis patients through blocking RANKL. An analysis …

Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown

Theses and Dissertations--Neuroscience

The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity …

Feasibility Of Integrating Tripterygium Wilfordii Into Modern Cancer Therapy For Increased Efficacy And Minimal Toxicity, Ngoc T. Vo

Undergraduate Research Posters

Cancer is the second leading cause of death in the U.S. and millions of novel cancer cases are being diagnosed each year. While chemotherapy and ionizing radiation are effective treatments against these malignant tumors, the adverse effects that accompany such treatments are devastating. In order to find alternative treatment methods with less side effects, we turn to Eastern herbal medicine. Recent scientific research has found that Tripterygium wilfordii, an herbal medicine traditionally used to treat inflammation in China, contains compounds (triptolide and celastrol) that prevent the growth of solid tumors, induce apoptosis, and prevent metastasis of developed tumors. Investigations …

Development Of A Multivalent Subunit Vaccine Against Tularemia Using Tobacco Mosaic Virus (Tmv) Based Delivery System, Sukalyani Banik, Ahd Ahmed Mansour, Ragavan Varadharajan Suresh, Sherri Wykoff-Clary, Meenakshi Malik, Alison A. Mccormick, Chandra Shekhar Bakshi

Faculty Publications & Research of the TUC College of Pharmacy

Francisella tularensisis a facultative intracellular pathogen, and is the causative agent of a fatal human disease known as tularemia. F. tularensis is classified as a Category A Biothreat agent by the CDC based on its use in bioweapon programs by several countries in the past and its potential to be used as an agent of bioterrorism. No licensed vaccine is currently available for prevention of tularemia. In this study, we used a novel approach for development of a multivalent subunit vaccine against tularemia by using an efficient tobacco mosaic virus (TMV) based delivery platform. The multivalent subunit vaccine was formulated …

A Molecular-Level View Of The Physical Stability Of Amorphous Solid Dispersions, Xiaoda Yuan

Theses and Dissertations--Pharmacy

Many pharmaceutical compounds being developed in recent years are poorly soluble in water. This has led to insufficient oral bioavailability of many compounds in vitro. The amorphous formulation is one of the promising techniques to increase the oral bioavailability of these poorly water-soluble compounds. However, an amorphous drug substance is inherently unstable because it is a high energy form. In order to increase the physical stability, the amorphous drug is often formulated with a suitable polymer to form an amorphous solid dispersion. Previous research has suggested that the formation of an intimately mixed drug-polymer mixture contributes to the stabilization …

Uji Stabilitas Fisik Formula Krim Yang Mengandung Ekstrak Kacang Kedelai (Glycine Max), Rosmala Dewi, Effionora Anwar, Yunita Ks

Pharmaceutical Sciences and Research

Soybean extract has known for its antiaging potential. The addition of soybean extract was predicted can influence the physical stability of the cream. Therefore, this research was aimed to test the physical stability of cream contained soybean extract in different concentration (2%, 4%, 6%, and 8%). The physical stability test including the storage for eight weeks at room temperature, high temperature (40°±2°C), and low temperature (4°±2°C). Stability parameters were the organoleptic observation, pH, globul size, viscosity, and cycling test. Those four cream formula showed good stability in organoleptic, pH, globul size, viscosity, and cycling test.

Efek Fraksi N-Heksana Kulit Hylocereus Polyhizus Terhadap Kadar Malondialdehida Tikus Stres Oksidatif, Wirna Maya Sari, Sri Wahdaningsih, Eka Kartika Untari

Pharmaceutical Sciences and Research

Excessive free radical production will lead to oxidative stress. One of the indicators used to determine stress oxidative is malondialdehyde (MDA). Hylocereus polyhizus peel is potential used natural exogenous antioxidant. The aim of this research was to study the effect of n-hexane fraction of H.polyhizus peel on MDA level and to determine the dose that could reduce the MDA level. H.polyhizus peel was macerated with chloroform, fractionated with n-Hexane. Rats were divided into 7 groups : normal, negative, positive control vitamin E (18 mg/ kgbw), positive control quercetin (4 mg/200gbw), H.polyhizus peel extract group treated with dose I (10mg/ 200gbw), …

Efek Fraksi N-Heksana Kulit Hylocereus Polyrhizus Terhadapaktivitas Katalase Tikus Stres Oksidatif, Eka Kartika Untari, Sri Wahdaningsih, Agustia Damayanti

Pharmaceutical Sciences and Research

Production of excess free radicals cause oxidative damage and degenerative diseases. Catalase enzyme is one of the endogenous intracellular antioxidant that can be reduced by oxidative stress conditions. The peel of red dragon fruit (Hylocereus polyrhizus) as a potent exogenous antioxidants could support the internal enzyme activity to prevent free radicals. The aim of this research was to determine the effect of n-hexane fraction of H.polyrhizus’s peel and the dose that could increase activity of catalase. The peel was maserated with chloroform, then fractionated by n-hexane. Stress condition was achieved by five days fasting and swimming for 10 mins/day to …

Formulasi Krim Antioksidan Ekstrak Etanol Daun Ubi Jalar Ungu (Ipomoea Batatas (L.) Lamk) Sebagai Anti Aging, Damaranie Dipahayu, Widji Soeratri, Mangestuti Agil

Pharmaceutical Sciences and Research

No abstract provided.

Antibakteri Fraksi N-Heksana Kulit Hylocereus Polyrhizus Terhadap Staphylococcus Epidermidis Dan Propionibacterium Acnes, Sri Wahdaningsih, Eka Kartika Untari, Yunita Fauziah

Pharmaceutical Sciences and Research

Acne can be caused by Staphylococcus epidermidis and Propionibacterium acnes. By using antibiotic for the acne theraphy in a long term period can cause resistance, organ detriment and imunohypersensitivity. Red dragon fruit’s peel (Hylocereus polyrhizus) is one of natural materials which can be used for alternative antibacterial. This study aims to determine the antibacterial activity of n-Hexane fraction of red dragon fruit’s peel against S. epidermidis dan P. acnes by the method of disc diffusion Kirby-Bauer. Red dragon fruit’s peel powder macerated within chloroform, and macerate then fractionated with n-Hexane. Phytochemical screening result red dragon fruit’s peel contains terpenoid and …

Cross-Sector Review Of Drivers And Available 3rs Approaches For Acute Systemic Toxicity Testing, Troy Seidle, Sally Robinson, Tom Holmes, Stuart Creton, Pilar Prieto, Julia Scheel, Magda Chlebus

Troy Seidle, PhD

Acute systemic toxicity studies are carried out in many sectors in which synthetic chemicals are manufactured or used and are among the most criticized of all toxicology tests on both scientific and ethical grounds. A review of the drivers for acute toxicity testing within the pharmaceutical industry led to a paradigm shift whereby in vivo acute toxicity data are no longer routinely required in advance of human clinical trials. Based on this experience, the following review was undertaken to identify (1) regulatory and scientific drivers for acute toxicity testing in other industrial sectors, (2) activities aimed at replacing, reducing, or …

The Fit-Hansa Demonstrates Reliability And Convergent Validity Of Functional Performance In Patients With Shoulder Disorders, Prajyot Kumta, Joy Macdermid, Saurabh Mehta, Paul Stratford

Saurabh Mehta

Study

DesignPsychometric study design.

Objectives

To assess the test-retest reliability and convergent validity of the Functional Impairment Test-Hand and Neck/Shoulder/Arm (FIT-HaNSA) in patients with shoulder disorders.

Background

Performance tests that assess functional ability of patients with shoulder disorders can provide useful information for making clinical or return-to-activity decisions. No performance-based shoulder test has yet demonstrated sufficient relevance or clinical measurement properties. The FIT-HaNSA examines upper extremity performance during repetitive tasks that emphasize shoulder reaching and static postures and, therefore, has greater relevance for assessing performance.

Methods

Thirty-six patients with shoulder disorders and 65 healthy controls were recruited for the study. …

Computer-Aided Drug Design And Discovery, Screening And Synthesis Of Small Molecule Inhibitors Of Nucleoside Transporters, Hilaire Colleen Playa

Theses and Dissertations (ETD)

Using prior biological data, pharmacophore models were made for hCNT1, hCNT3, hENT1, and hENT4. The hCNT3 and hCNT1 pharmacophore were used to select compounds for biological testing. The NBMPR analogue and dipyridamole analogue hENT1 pharmacophores were compared to each other and to a combined pharmacophore for hENT1. The dipyridamole analogue pharmacophore better predicted non-nucleoside small molecule inhibitors, and as such appears to be the better tool for aiding in the design of new small molecule inhibitors. The hCNT3 pharmacophore failed to select active compounds and as such must be redesigned. The hCNT1 pharmacophore succeeded in identifying two moderately active compounds …

Nucleoside Reverse Transcriptase Inhibitors Possess Intrinsic Anti-Inflammatory Activity, Benjamin J. Fowler, Bradley D. Gelfand, Younghee Kim, Nagaraj Kerur, Valeria Tarallo, Yoshio Hirano, Shoba Amarnath, Daniel H. Fowler, Marta Radwan, Mark T. Young, Keir Pittman, Paul Kubes, Hitesh Agarwal, Keykavous Parang, David R. Hinton, Ana Bastos-Carvalho, Shengjian Li, Testuhiro Yasuma, Takeshi Mizutani, Reo Yasuma, Charles Wright, Jayakrishna Ambati

Pharmacy Faculty Articles and Research

Nucleoside reverse transcriptase inhibitors (NRTIs) are mainstay therapeutics for HIV that block retrovirus replication. Alu (an endogenous retroelement that also requires reverse transcriptase for its life cycle)–derived RNAs activate P2X7 and the NLRP3 inflammasome to cause cell death of the retinal pigment epithelium in geographic atrophy, a type of age-related macular degeneration. We found that NRTIs inhibit P2X7-mediated NLRP3 inflammasome activation independent of reverse transcriptase inhibition. Multiple approved and clinically relevant NRTIs prevented caspase-1 activation, the effector of the NLRP3 inflammasome, induced by Alu RNA. NRTIs were efficacious in mouse models of geographic atrophy, choroidal neovascularization, graft-versus-host disease, and sterile …

Considering A New Paradigm For Alzheimer’S Disease Research, Gillian R. Langley

Gill Langley, PhD

Using Alzheimer’s disease as a case study, this review argues that it might be time to consider a new paradigm in medical research and drug discovery. The existing framework is overly dependent on often unvalidated animal models, particularly transgenic mice. Translational success remains elusive and costly late-stage drug failure is common. The conventional paradigm tends to overlook species differences and assumes that animal-based findings are generally applicable to humans. Could pathways-based research using advanced human-specific models probed with new tools, including those of systems biology, take centre stage? The current transition in chemical toxicology to a 21st-century paradigm could be …

Are Elevated Vancomycin Serum Trough Concentrations Achieved Within The First 7 Days Of Therapy Associated With Acute Kidney Injury In Children?, Chad A. Knoderer, Kristen R. Nichols, Kelsey C. Lyon, Megan M. Veverka, Amy C. Wilson

Chad A. Knoderer

Background In 2008, the empiric vancomycin dosing recommendation in children at our institution was changed from 40 to 60 mg/kg per day. Subsequently, an increased incidence of acute kidney injury (AKI) in patients receiving vancomycin was suspected. The objective of this study was to evaluate AKI in children receiving vancomycin and to determine risk factors for AKI development. Methods Medical records of patients aged 30 days through 17 years who received vancomycin for at least 72 hours between January and December 2007 (40 mg/kg per day) and January and December 2010 (60 mg/kg per day) were reviewed. Patients with cystic …