Open Access. Powered by Scholars. Published by Universities.®
- Keyword
-
- Pharmacokinetics (3)
- Bioavailability (2)
- Liposomal ciprofloxacin (2)
- Older adults (2)
- Opioid (2)
-
- Sickle cell disease (2)
- 3D Virtual Screening (1)
- 5-Hydroxymethyl furfural (1)
- AIDS (1)
- Acute Myocardial Infarction (1)
- Adherence (1)
- Alcohol (1)
- Allosteric (1)
- Allosteric effectors of hemoglobin (1)
- Alpha4beta2 (1)
- Alveolar macrophages (1)
- Analgesics (1)
- Anti-inflammation (1)
- Antitubulin (1)
- Aspirin (1)
- Attenuation (1)
- Beta-blockers (1)
- Bidirectional Transmucosal Apparatus (BTA) (1)
- Biorelevant In Vitro Testing (1)
- Bisphosphonates (1)
- Bivalent (1)
- Black box warning (1)
- CCR5 (1)
- Calu-3 (1)
- Cellular uptake (1)
Articles 1 - 23 of 23
Full-Text Articles in Medicine and Health Sciences
Tobramycin Disposition In The Lung Following Airway Administration, Min Li
Tobramycin Disposition In The Lung Following Airway Administration, Min Li
Theses and Dissertations
Tobramycin disposition following airway administration was evaluated by meta-analysis of human data in the literature and, experimentally, using a realistic ex vivo model, the isolated perfused rat lung preparation (IPRL). Pulmonary bioavailability of inhaled tobramycin in published studies was re-evaluated separately for CF and healthy adults, with the drug’s intrinsic pharmacokinetic (PK) parameters obtained from intravenous (IV) studies in the literature. While large variations in tobramycin’s clearance precluded accurate assessment of its bioavailability, the results were indicative of substantial pulmonary absorption, in spite of its hydrophilic and poly cationic properties. To explore its disposition kinetics and mechanisms following airway administration, …
Alcohol And Medication Use In Community-Dwelling Older Adults: Understanding The Effect Of Alcohol And Central Nervous System-Acting Medications On The Risk For Falls, Maitreyee Mohanty
Alcohol And Medication Use In Community-Dwelling Older Adults: Understanding The Effect Of Alcohol And Central Nervous System-Acting Medications On The Risk For Falls, Maitreyee Mohanty
Theses and Dissertations
Introduction: Aging, comorbid conditions, and use of medications render older adults more susceptible to alcohol-disease or alcohol-drug interactions that may lead to harmful outcomes. In this dissertation project the risk profile of alcohol and medications use among older adults was investigated. Considering the rise in CNS-acting medication use and the adverse effect profile linked to CNS-acting medications, it was also of interest to find if older adults were at risk of falling due to interactions between alcohol and CNS-acting medication. Objectives: The objectives were as follows: 1) to determine the prevalence, pattern and factors associated with at-risk drinking, 2) to …
Assessment Of The Drug-Drug Interaction Potential Of Anionic Components In The Diet And Herbal Medicines On Organic Anion Transporters (Slc22 Family), Li Wang
Theses and Dissertations
Numerous natural products are widely used as first-line/alternative therapeutics and dietary supplements in both western and eastern society. However, the safety and efficacy profiles for herbal products are still limited. Organic anion transporters (OATs; SLC22 family) are expressed in many barrier organs and mediate in vivo body disposition of a broad array of endogenous substances and clinically important drugs. As some dietary flavonoids and phenolic acids were previously demonstrated to interact with OATs, it is necessary to explore the potential interaction of such components found in natural products in order to avoid potential OAT-mediated drug-drug interactions (DDIs). The inhibitory effects …
A Novel Biorelevant In Vitro System To Predict The In Vivo Performance Of Oral Transmucosal Products, Poonam Delvadia
A Novel Biorelevant In Vitro System To Predict The In Vivo Performance Of Oral Transmucosal Products, Poonam Delvadia
Theses and Dissertations
In vitro dissolution, release and permeation testing is a common practice during drug product research and development. These in vitro tests, if predictive, are referred to as biorelevant tests and can play diverse roles to facilitate and expedite product development in a cost effective manner. Oral transmucosal products (OTPs) are currently tested using compendial and modified in vitro tests which may or may not be good predictors of in vivo performance due to a lack of biorelevance. A critical need for a broadly applicable and biorelevant in vitro system for OTPs has been expressed in the literature and the goal …
Synthesis, Testing And Crystallographic Studies Of Allosteric Modifiers Of Hemoglobin, Tanvi Deshpande
Synthesis, Testing And Crystallographic Studies Of Allosteric Modifiers Of Hemoglobin, Tanvi Deshpande
Theses and Dissertations
The major physiological function of hemoglobin (Hb) is to bind, transport and deliver oxygen to tissues; made efficient by endogenous effectors, such as protons and 2,3-diphosphoglycerate. Synthetic allosteric effectors of Hb (AEHs) are also known to modulate Hb oxygen affinity, showing potential for the treatment of sickle cell disease (SCD) and ischemic-related diseases. In this project, AEHs which increase Hb affinity for oxygen, including derivatives of the anti-sickling compounds, 5HMF and benzaldehydes, as well as an AEH that decreases Hb affinity for oxygen, RSR-13, were synthesized for their effects on Hb oxygen binding property and their capability to release NO …
Development And Evaluation Of The Assessment Of Opioid Taking Behaviors And Adherence Scale (Aotba) In Patients With Sickle Cell Disease, Abdulkhaliq Jassem Alsalman
Development And Evaluation Of The Assessment Of Opioid Taking Behaviors And Adherence Scale (Aotba) In Patients With Sickle Cell Disease, Abdulkhaliq Jassem Alsalman
Theses and Dissertations
The rapid growth in opioid therapy for non-cancer pain has occurred without an adequate appreciation of the consequences of this growth. Few studies provide patient-centered evidence that can be used to inform the current proposed standards for efficacious (safe and effective) opioid prescribing in non-cancer pain. Furthermore, different terms may be used interchangeably in the literature to refer to opioid-taking behaviors, resulting in imprecise or vague interpretation of existing evidence. We therefore sought to explore patterns of opioid-taking behavior and their biopsychosocial-spiritual determinants in African-American adults with sickle cell disease (SCD). Many questions surround opioid use for non-cancer pain, but …
Reverse-Phase Ion-Pairing Ultra Performance Liquid Chromatography-Mass Spectrometry In Characterization And Fingerprinting Of Diverse Sulfated Glycosaminoglycan Mimetics, Pooja Ponnusamy
Theses and Dissertations
Heparin is a highly sulfated glycosaminoglycan with potent anticoagulant, antimetastatic, and anti-inflammatory effects. Polymeric and polyanionic nature of heparin makes dosing and side effects a nightmare for healthcare professionals. Our laboratory has proposed appropriately designed, small, highly sulfated aromatic molecules as potential mimetics of heparin. These easier-to-synthesize small molecules have been shown to possess interesting pharmacological and improved toxicological profiles. However, the detection and characterization of these highly sulfated molecules is challenging. A robust RP-IP UPLC-MS method was developed to successfully retain, resolve and quantify sulfated non-saccharide GAG mimetics without the requirement of pre- or post- column derivatization. Comparative analysis …
The Development And Applications Of The Hint Scoring Function: Exploring Colchicine-Site Anticancer Agents And Tautomerism, Chenxiao Da
Theses and Dissertations
The overall aim of this work was to apply HINT, an empirical scoring function based on the understanding of hydrophobicity, to analyze and predict the binding affinities and biological activities of colchicine-site anticancer agents. The second, concurrent aim was to improve the scoring function by incorporating tautomerism within the modeling process. Our belief is that proper evaluation of tautomeric forms for small molecules will improve performance of virtual screening. The novel pyrrole-based compounds targeting the colchicine site were docked into the receptor using HINT as a rescoring function. Two distinct binding modes dictated by the size and shape of a …
Risk Factors For Postoperative Cognitive Dysfunction In Older Adults Undergoing Major Noncardiac Surgery, Osama Shoair
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 …
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) …
Acute Pharmacological Treatment Given To Older Adults With Acute Myocardial Infarction: A Nationwide Emergency Department Study, 1992-2010, Maryam S. Alowayesh
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 …
Development Of Antagonists Targeting Chemokine Receptor Ccr5 And The Chemokine Receptor Ccr5 – Mu Opioid Receptor Heterodimer, Christopher Kent Arnatt
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 …
Kinetic And Thermodynamic Studies Of Thrombin Inhibitors, Aziz May Abdel
Kinetic And Thermodynamic Studies Of Thrombin Inhibitors, Aziz May Abdel
Theses and Dissertations
Sulfated low molecular weight lignins (LMWLs), CDSO3 and FDSO3, designed recently as macromolecular mimetics of heparin, were found to exhibit potent anticoagulant activity. Small molecules based on the same scaffold, SBD and SBT, showed promising thrombin inhibition. We were able to address the mechanism of the inhibition using Michaelis-Menten kinetics. All the molecules were found to be allosterically impairing thrombin activity using either noncompetitive or uncompetitive mechanism. Absence of competition with hirugen, an exosite 1 ligand, and competition with polymeric heparin points to exosite 2 as the site of interaction for these inhibitors. Yet mixed competition results with other exosite …
Positive Allosteric Modulators Of Alpha4beta2 Neuronal Nicotinic Receptors: Synthesis And In Vitro Studies, Atul Jain
Theses and Dissertations
des-Formylflustrabromine (dFBr), isolated from the marine organism Flustra foliacea, is the first selective, positive allosteric modulator (PAM) of α4β2 nicotinic acetylcholine receptors that potentiates the action of the neurotransmitter acetylcholine (ACh). Most agonists for this receptor population are not selective and can activate other nACh receptors. A selective PAM, which activates α4β2 nACh receptors only in the presence of ACh, might find application in the treatment of of various neurological diseases such as Alzheimer’s disease or autism. dFBr was examined and found to produce a biphasic dose-response curve over a wide concentration range (i.e., potentiation at low concentration, but inhibition …
Impacts Of Black Box Warning, National Coverage Determination, And Risk Evaluation And Mitigation Strategies On The Inpatient On-Label And Off-Label Use Of Erythropoiesis-Stimulating Agents, Arpamas Seetasith
Theses and Dissertations
Background: FDA black box warning, Risk Evaluation and Mitigation Strategies (REMS), and CMS national coverage determination (NCD) aim to reduce inappropriate use of erythropoiesis-stimulating agents (ESAs) that are widely used in anemic patients. Previous studies have not linked specific safety interventions to changes in ESA utilization patterns in the inpatient settings nor assessed such interventions on off-label use of the drugs. Ineffectiveness of the intervention and lag time between such interventions and the observed change in clinical practice could lead to serious clinical outcomes. In addition, such interventions may unintentionally reduce on-label and some off-label use of ESAs considered “appropriate” …
Design, Syntheses, And Biological Evaluation Of 14-N-Substituted Naltrexone Derivatives As Opioid Receptor Ligands, Orgil Elbegdorj
Design, Syntheses, And Biological Evaluation Of 14-N-Substituted Naltrexone Derivatives As Opioid Receptor Ligands, Orgil Elbegdorj
Theses and Dissertations
Opium, the dried resin obtained from the unripe seedpods of the poppy flower, has been used for medicinal and euphoric purposes since ancient times. Morphine, the main active ingredient of opium, and other clinically useful opioid analgesics all mediate their effects through activating the mu opioid receptor. Studies involving the mu opioid receptor knockout mice showed that the interaction with the mu opioid receptor is also responsible for many notorious side effects associated with these drugs including dependence and addiction. Therefore, selective antagonists for the mu opioid receptor are needed to study its function in drug abuse and addiction. Previously, …
Defining A Simplified Pharmacophore For Simocyclinone D8 Inhibition Of Dna Gyrase, Lauren Gaskell
Defining A Simplified Pharmacophore For Simocyclinone D8 Inhibition Of Dna Gyrase, Lauren Gaskell
Theses and Dissertations
The type II topoisomerase subfamily of enzymes has been clinically targeted by the widely used, broad-spectrum quinolone class of antibacterials. Due to emerging drug-resistant strains of bacteria, the quinolones’ effectiveness is threatened. The natural product simocyclinone D8 (SD8) has shown the ability to inhibit the type II topoisomerase, DNA gyrase, even when mutated to be resistant to the quinolones. In order to determine the pharmacophore required for SD8 binding to DNA gyrase, 16 compounds were synthesized. These compounds were then tested by surface plasmon resonance for their ability to inhibit the DNA – DNA gyrase binding interaction. It was found …
Kinetics And Mechanisms Of Accumulation For Liposomal Ciprofloxacin Into Rat Alveolar Macrophages, Sayeed Mossadeq
Kinetics And Mechanisms Of Accumulation For Liposomal Ciprofloxacin Into Rat Alveolar Macrophages, Sayeed Mossadeq
Theses and Dissertations
The kinetics and mechanism of accumulation for liposomal ciprofloxacin (Lipo-CPFX) into the rat alveolar macrophage NR8383 cells were studied in vitro, in comparison to unformulated ciprofloxacin (CPFX). Upon incubation with CPFX or Lipo-CPFX, cellular drug accumulation was determined from the cell lysates or efflux was from the extracellular media by fluorescence-HPLC. The accumulation for Lipo-CPFX reached the asymptotic values at ≥ 2 hours, which was a result of uptake and efflux. The uptake appeared to be due to liposomes, mediated via cellular energy-independent mechanism like lipid fusion. In contrast, the efflux appeared to be due to ciprofloxacin, partly cellular energy-dependent, …
Prevalence Of Anti-Diabetic And Antilipidemic Medications In Children And Adolescents Treated With Atypical Antipsychotics In A Virginia Medicaid Population, Della Varghese
Theses and Dissertations
Objective: To determine if the prevalence of anti-diabetic and antilipidemic medication use among children treated with atypical antipsychotics is higher than those not treated with antipsychotics. Methods: Virginia Medicaid beneficiaries (2-17 years) continuously enrolled from August 1, 2010 to July 31, 2011 with at least two prescription claims for atypical antipsychotics were the exposed group. All other subjects during the study period were the non-exposed group. Prevalence of anti-diabetic and antilipidemic medication use in both groups were computed and compared using Chi-square test (α=0.05). Results: A total of 299,593 and 4,922 subjects were identified as the non-exposed and exposed groups, …
Assessment Of The Feasibility Of Co-Administration Of Phenolic Dietary Compounds With Phenylephrine To Increase Its Bioavailability, Zhenxian Zhang
Assessment Of The Feasibility Of Co-Administration Of Phenolic Dietary Compounds With Phenylephrine To Increase Its Bioavailability, Zhenxian Zhang
Theses and Dissertations
R-(-)-Phenylephrine (PE) is the most commonly used nonprescription oral nasal decongestant in the United States. It is a selective α1-adrenergic receptor agonist and has many years of safe usage. However, the efficacy of PE is controversial, due to its extensive pre-systemic metabolism, which leads to low and variable oral bioavailability (38 ± 9%, mean ± SD). Sulfation plays a very important role in pre-systemic metabolism of PE. The sulfation of PE occurs at its phenolic group, which is the preferred structural feature of many sulfotransferase (SULT) substrates. Compounds with phenolic groups have similar structures to PE, which may share the …
In-Vitro Pk/Pd Profiling And Modeling Of The Anti-Sickling Agents, 5-Hydroxymethyl Furfural (5-Hmf) And Novel Synthetic Allosteric Effectors Of Hemoglobin (Aeh) In Human Whole Blood, Apurvasena Parikh
Theses and Dissertations
Introduction. 5-HMF and novel INN-compounds are left-shifting AEH, shown to have anti-sickling action by forming transiently covalent Schiff-base adducts with hemoglobin (Hb), thereby increasing the Hb O2-affinity. They are hypothesized to be substrates for aldehyde dehydrogenase (ALDH) in the liver and red blood cells (RBC). Methods. Biopharmaceutical assessments were made for AEH, using calculated physicochemical properties. Their in-vitro hepatic metabolism (mediated by ALDH) was characterized using hepatic cytosol, and in-vitro-in-vivo extrapolations (IVIVE) were made. Inter-species differences in hepatic cytosolic ALDH activity were investigated using acetaldehyde as a model substrate in different mammalian species. Time- and concentration-dependent in-vitro disposition of 5-HMF …
In Vitro Lung Epithelial Cell Transport And Anti-Inflammatory Activity For Liposomal Ciprofloxacin, Ruba Darweesh
In Vitro Lung Epithelial Cell Transport And Anti-Inflammatory Activity For Liposomal Ciprofloxacin, Ruba Darweesh
Theses and Dissertations
Liposomal ciprofloxacin (Lipo-CPFX) is being developed for inhalation, with a goal of sustaining the therapeutic activity, compared to unformulated ciprofloxacin (CPFX). However, the kinetics and mechanism of its sustained local lung retention and pharmacological activity are yet to be fully characterized. This project hypothesized that Lipo-CPFX enables slower and sustained lung epithelial transport and uptake, compared to CPFX, thereby producing prolonged local pharmacological actions. The human bronchial epithelial Calu-3 cells were used as monolayers to characterize the kinetics and mechanism of transport and/or uptake, and to assess the effects of such slow kinetics for Lipo-CPFX on its inhibition against lipopolysaccharide …
Association Between Concomitant Use Of Bisphosphonates And Serotonin Reuptake Inhibitors And Increased Risk Of Osteoporotic-Related Fractures: Among Community-Dwelling Postmenopausal Women, Abner Nyandege
Theses and Dissertations
Osteoporosis and depression are prevalent among older postmenopausal women 65 years or older. Bisphosphonates (BPs) and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) are commonly used medications to treat these conditions. Inhibitory effects of BPs on osteoclasts are responsible for the reduction in fracture risk. SSRIs, however, are associated with increased fracture risk through decreasing osteoblasts and increasing osteoclastic activity. These effects of SSRIs could attenuate the beneficial effects of BPs. This dissertation describes the concomitant use of BPs and SSRIs among postmeopausa women and reports findings from examining the association between concomitant use of BPs …