Digital Commons Network^™

Organic Anion And Cation Transporter Expression And Function During Embryonic Kidney Development And In Organ Culture Model Systems, Douglas H. Sweet, Satish A. Eraly, Kevin T. Bush, Sanjay K. Nigam

Pharmaceutics Publications

Background

Organic anion and cation transporters (OATs, OCTs and OCTNs) mediate the proximal tubular secretion of numerous clinically important compounds, including various commonly prescribed pharmaceuticals. Here, we examine the ontogeny of these transporters in rat embryonic kidney in detail, both in vivo and in two in vitro organ culture models of kidney development, whole embryonic kidney (WEK) culture and culture of induced metanephric mesenchyme (MM).

Methods

We used QPCR to determine expression levels of transporter genes in rat embryonic kidneys on each day of gestation from ed13 to ed18, in induced and un-induced MM, and on each day of one …

Characterization Of Perphenazine And Scopolamine Aerosols Generated Using The Capillary Aerosol Generator, Xihao Li

Theses and Dissertations

The characterization of perphenazine and scopolamine aerosols generated using the capillary aerosol generator (CAG) was reported. Variables including steady state power, the formulation vehicle, the drug concentration and the formulation flow rate were studied for their effects on the chemical stability and particle size of these drug aerosols.Stability-indicating HPLC and LC-MS assays were developed and validated for perphenazine and scopolamine, respectively. The chemical stability of each compound was investigated under a variety of stress conditions and the structure of degradation products was proposed.Perphenazine aerosols were generated from propylene glycol (PG) formulations with concentrations of 9, 48 and 90mM at formulation …

Surgical Infection Society Guidelines For Vaccination After Traumatic Injury, Thomas R. Howdieshell, Daithi Heffernan, Joseph T. Dipiro

Publications from the Office of the Dean

Background: Recommendations for vaccination of injured patients against infection are evolving. Newly-recognized infections, safety considerations, changing epidemiology, and redefinition of patient groups at risk are factors that may influence vaccine development priorities and recommendations for immunization. However, recommendations must often be formulated based on incomplete data, forcing reliance on expert opinion to address some crucial questions. These guidelines provide evidence-based recommendations for the prevention or treatment of infectious morbidity and mortality after traumatic injury, such as soft tissue wounds, human or animal bites, or after splenectomy.

Methods: A panel of experts conducted a thorough review of published literature, …

Interspecies Pharmacokinetic Scaling And Metabolism Of Alcohols And Glycols, Pankaj Gupta

Theses and Dissertations

Background: Despite the numerous pharmaceutical applications of alcohols andglycols, the interspecies differences with respect to their pharmacokinetics (PK) arepoorly understood. The aim of this research was to use in-vivo and in-vitro approaches to compare and model the PK characteristics across various species.Methods: Appropriate published in-vivo studies (in different species) foralcohols and glycols were carefully selected. PK analysis was performed using (a) noncompartmental analysis and (b) compartmental modeling to estimate relevant dose-independent PK parameters. Next, six alcohols (methanol, ethanol, 1 -propanol, 1 -butanol, 1-hexanol, and 1-octanol), two glycols (ethylene glycol and propylene glycol)and one secondary alcohol (2-propanol) were examined as in-vitro …

Length Of Hospital Stay, Delirium And Discharge Status Outcomes Associated With Anticholinergic Drug Use In Elderly Hospitalized Dementia Patients, Kelly J. Gauthier

Theses and Dissertations

Problem: There are a significant proportion of patients taking acetylcholinesterase inhibitors (ChEi) for cognitive dysfunction also taking medications with anticholinergic (ACh) properties that may counteract their effects. As the number of ACh medications, burden, increases so does the likelihood of an adverse outcome.Background: ACh medications are frequently used in the elderly population (Carnahan 2004) even those with dementia or AD (Roe et al., 2002; Giron et al., 2001; Altavela 2003; Gill et al., 2005; Kogut et al., 2005). Methods: Hospitalized patients > 65 years of age with dementia (AD, other dementias, or with inferred dementia based on ChEi or NMDA antagonist …

A 'Biorelevant' Approach For Accelerated In Vitro Release And In Vitro-In Vivo Relationship Of A Biodegradable, Naltrexone Implant, Sunil S. Iyer

Theses and Dissertations

Characterization of in vitro and in vivo drug release profiles constitutes an important step in developing and optimizing an effective, long acting delivery system for naltrexone. Accelerated in vitro methods are also important for quality assurance of manufactured dosage forms. For drug release testing of sustained release parenteral dosage forms, the modified USP Apparatus 4 (flow-through cell) has been recommended by the The Fédération Internationale Pharmaceutique/American Association of Pharmaceutical Scientists (FIP/AAPS) Guidelines. Details on such studies however, are generally not found in the literature. To incorporate 'biorelevance' to implant drug release studies, this research investigated an approach to apparatus design …

Small Molecules Binding To Serpins, Junaid Afridi

Theses and Dissertations

Serpins are a unique breed of proteins due to their enzymatic mechanism. Two systems were closely monitored during fluorescent binding studies, the ACT-CHY along with the AT:TRY interaction. Four different conformational variants of each system were studied including the native, cleaved, latent and complex forms. Three different fluorescent dyes were used to identify the conformations including ANS, TNS, and bis-ANS. SI studies and protease assays utilizing both Suc-AAPF-pNA and L-BAPNA were instrumental in determining conformations along with gel electrophoresis studies. The hydrophobic dyes bound to the different serpins with varying KD and ΔFmax due to structural variations among the conformers …

The Effect Of Variability In Substance Abuse And Dependence Terminology On Physicians' Prescribing Decisions, Lisa Rochelle Burroughs Phipps

Theses and Dissertations

Prescription drug abuse is a continuing problem in the United States. Educating physicians on issues related to prescription drug abuse is a key factor in preventing and treating this problem. High variability has been found in substance abuse terminology in the literature, textbooks, and FDA-approved product labeling. This dissertation describes a survey study designed to address how the variability in substance abuse terminology, specifically package inserts, affects the prescribing decisions made by physicians.A random sample of 1008 physicians currently licensed and residing in the Commonwealth of Virginia received a letter of explanation, a self-administered questionnaire, and a follow-up reminder and …