Digital Commons Network^™

Enhancement Of The Placental Transmission Of Lopinavir Using A Transporter Targeted Prodrug Strategy, Meng Wang

Theses and Dissertations

Lopinavir (LPV) is a potent protease inhibitor specific for HIV-1. However, LPV has poor placental penetration due to substrate activity for efflux transporter by P-glycoprotein (P-gp). Since fatty acid transporters are highly expressed in the placenta during pregnancy, we designed fatty acid ester prodrug of lopinavir as substrates of fatty acid transporter in order to improve their uptake into placenta. Seven dicarboxylic acid esters of lopinavir have been made in our lab. The structures were characterized by ¹H-NMR, ¹³C-NMR, LC-MS/MS, HRMS, IR and melting points. After making the prodrugs, an LC-MS/MS method with high specificity and sensitivity, as …

Orientia Tsutsugamushi Ankyrin-Repeat Protein Family Targeting Of The Host Endoplasmic Reticulum, Lauren Viebrock

Theses and Dissertations

Abstract

ORIENTIA TSUTSUGAMUSHI ANKYRIN REPEAT-PROTEIN FAMILY TARGETING OF THE HOST ENDOPLASMIC RETICULUM

By Lauren VieBrock, B.S.

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University

Virginia Commonwealth University, 2015

Director: Jason A. Carlyon, Ph.D.

Professor

Microbiology and Immunology

Scrub typhus is an understudied, potentially fatal febrile illness, which poses threat to one billion people annually in the Asia-Pacific region. The host-pathogen interactions that facilitate the intracellular survival of the etiologic agent, Orientia tsutsugamushi, are not well understood. The Orientia tsutsugamushi genome encodes a large number of ankyrin repeat-containing proteins …

Incorporation Of Molecular Diagnostics Into Medical Laboratory Science Curriculum: Clinical Facilities Expectations. An Asynchronous, Iterative, Online Delphi Study., Barbara Kraj

Theses and Dissertations

The medical laboratory science (MLS) profession is in need for published molecular diagnostics competency-based standards and curriculum. To assess their expectations of new MLS graduates, professionals performing and supervising performance of clinical molecular assays were surveyed to rate the importance of relevant cognitive and psychomotor learning objectives. A modified, asynchronous, iterative online Delphi process was utilized for assessment of consensus on the importance of the objectives. The survey was delivered through online REDCap application. Program directors of 221 MLS programs accredited by the National Accrediting Agency for Clinical Laboratory Science (NAACLS) were asked to forward the first Delphi survey to …

General Dentists' Role In Providing Care To Very Young Children:Pediatric Dentists' Perspective, Shinjni Razdan

Theses and Dissertations

To examine the pediatric dentists’ perspective on level of care to children 0-3 years old by general dentists, an electronic survey was sent out to 5185 AAPD members and 769 responded (response rate: 14.8%). Forty-six percent agreed with a general dentist providing a dental home to children 0-3 years old. Only 24% agreed that general dentists could perform complex restorative and behavior management procedures for 0-3 years old. Younger respondents, pediatric dentists who practice in rural areas or teaching pediatric dentistry, and those who perceived adequate exposure during dental school were more likely to agree on general dentists proving a …

The Effect Of Dexamethasone On Il-33-Mediated Mast Cell Activation, Oksana I. Chernushevich

Theses and Dissertations

Dexamethasone has been shown to inhibit IgE-mediated mast cell activation, and the present research investigated its role in suppressing IL-33-mediated mast cell activation. We have found that micromolar concentrations of Dexamethasone are capable of suppressing IL-33-mediated mast cell cytokine production, on several genetic backgrounds, and in not only bone marrow derived mast cells, but also peritoneal mast cells. Intracellular staining demonstrated that Dexamethasone significantly reduces expression of the IL-33 receptor, T1/ST2, in mast cells; however, the cytokine suppression is independent of T1/ST2 downregulation. At the same time, Dexamethasone pretreatment significantly reduced ERK phosphorylation, but our data suggests that inhibition occurs …

The Role Of Adam10, Adam17, And Spag6 In Humoral Immunity And Secondary Lymphoid Tissue Architecture, Lauren Folgosa Cooley

Theses and Dissertations

ADAM10, ADAM17, and SPAG6 contribute significantly to humoral immunity and secondary lymphoid tissue architecture. ADAM10 and ADAM17 are two closely related zinc-metalloproteinases. Through cleavage of their ligands CD23 and TNF, respectively, they greatly influence IgE production and secondary lymphoid tissue architecture maintenance. Th1 prone WT strains initially exhibit increased ADAM17 and TNF yet reduced ADAM10 relative to Th2 prone WT strains. In the absence of B cell ADAM10, a compensatory increase in ADAM17 and TNF cleavage is noted only in Th1 prone C57Bl/6, not Th2 prone Balb/c. B cell TNF homeostasis is important for maintaining secondary lymphoid tissue architecture. We …

A Continuous Process Towards The Synthesis Of Quinolones, Stevara N. Clinton

Theses and Dissertations

Abstract

The development of quinolones is described from the first quinolone to the latest fluoroquinolones. Quinolones have generated considerable interest since their discovery because of their antibacterial capabilities. Analogs incorporating the 4-quinolone ring system comprise a largely expanding group of synthetic compounds. The development of antibacterial resistance has created the need for an efficient synthesis of quinolones that can be easily adapted toward the assembly of quinolone based antibacterial drugs.

There are several reported approaches to the 4-quinolone ring system. Many of these methods use expensive starting materials, require the removal of high boiling solvents, or use high temperature conditions …

Development Of Novel Chimeric Epitope Based Diagnostic Antigens And Vaccines For Lyme Disease, Lee D. Oliver Jr.

Theses and Dissertations

Lyme disease (LD) is the leading arthropod-borne disease in North America with 300-600,000 cases each year. There are currently no approved human LD vaccines. Outer surface protein C (OspC) has emerged as a leading vaccine candidate and an attractive diagnostic marker due to its antigenicity and expression early in infection. Several chimeric, epitope based OspC derived proteins were generated. The constructs were found to be highly immunogenic in mice and vaccination induced complement-dependent bactericidal antibodies. These results suggest that a broadly protective polyvalent OspC epitope based vaccine can be produced. Currently, LD diagnostic approaches are unreliable and unable to differentiate …

Influences Of Flunixin And Tenoxicam On The Pharmacokinetics Of Florfenicol In Lipopolysaccharide-Induced Endotoxemia, Feri̇de Koç, Alptuğ Ati̇la, Emre Karakuş, Kami̇l Üney

Turkish Journal of Veterinary & Animal Sciences

The purpose of this study was to investigate the influences of flunixin (FM) and tenoxicam (TN) on the pharmacokinetics of florfenicol (FF) after coadministration in lipopolysaccharide (LPS)-induced endotoxemic rabbits. Fifteen male rabbits were used in this study. FF (20 mg/kg), FM (2 mg/kg), and TN (1 mg/kg) were coadministered via intravenous injection to the animals. The concentrations of FF were determined by high-performance liquid chromatography with diode-array detection from 0.08 to 12 h in plasma. The plasma concentration-time profile of FF was described using a noncompartmental open model. In this study, terminal half-life, area under the curve, mean residence time, …

Seroepidemiological Survey Of Leptospiral Infection In Stray Dogs In Serbia, Dragica Vojinovic, Natasa Bogicevic, Ana Vasic, Marija Manic, Milica Elezovic Radovanovic, Dragan Rogozarski, Jovan Maric, Miroslav Valcic

Turkish Journal of Veterinary & Animal Sciences

Leptospirosis is a bacterial zoonosis with worldwide distribution. This disease is facilitated among stray dogs due to their lifestyle and the absence of immunoprophylaxis. The aim of the present study was to provide serological data on the presence of certain serovars of Leptospira spp., which are assumed to circulate in the population of stray dogs in Serbia. During a period of 3 years (from April 2010 to June 2013), 1045 canine sera originating from 11 shelters were submitted to the laboratory of the Department of Infectious Animal Diseases and Diseases of Bees, Faculty of Veterinary Medicine, Belgrade. A microscopic agglutination …

Determination Of Serum Cardiac Biomarkers And Plasma D-Dimer Levelsin Anemic Sheep With Babesiosis, Özlem Orunç Kilinç, Yaşar Göz, Nazmi̇ Yüksek, Yildiray Başbuğan, Ali̇ Bi̇lgi̇n Yilmaz, Ahmet Duran Ataş

Turkish Journal of Veterinary & Animal Sciences

In this study, the cardiac effects of anemia and venous thromboembolism (VTE), reportedly caused by the hemolyzed erythrocytes occurring in sheep with babesiosis, were investigated using cardiac markers and D-dimer (DD). The study included 34 sheep: 24 infected Akkaraman sheep (1-3 years old, diagnosed with babesiosis based on clinical and laboratory findings) and a control group of 10 noninfected healthy sheep of the same breed and age. Hematocrit (Hct) levels were measured in blood obtained from both groups. Cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and aspartate aminotransferase (AST) levels were measured in serum samples. In addition, the levels of …

Hospital Preparedness In Community Measles Outbreaks-Challenges And Recommendations For Low-Resource Settings, Sadia Shakoor, Fatima Mir, Anita Zaidi, Afia Zafar

Department of Pathology and Laboratory Medicine

We have reviewed various strategies involved in containment of measles in healthcare facilities during community outbreaks. The strategies that are more applicable to resource-poor settings, such as natural ventilation, mechanical ventilation with heating and air-conditioning systems allowing unidirectional air-flow, and protection of un-infected patients and healthcare workers (HCWs), have been examined. Ventilation methods need innovative customization for resource-poor settings followed by validation and post-implementation analysis for impact. Mandatory vaccination of all HCWs with two doses of measles-containing vaccine, appropriate post-exposure prophylaxis of immunocompromised inpatients, and stringent admission criteria for measles cases can contribute toward reduction of nosocomial and secondary transmission …

Parasites Within Parasites: Transmission And Evolution Of Neorickettsia In Digeneans, Stephen Edward Greiman

Theses and Dissertations

Digeneans are endoparasitic flatworms with complex life cycles that involve two or more different animals as definitive and intermediate hosts. Some digenean species harbor bacterial endosymbionts belonging to the genus Neorickettsia (Order: Rickettsiales, Family: Anaplasmataceae). Neorickettsia occur in all life cycle stages of digeneans and are maintained by vertical transmission. Far from benign however, Neorickettsia may also be transmitted horizontally by digenean parasites to their vertebrate definitive hosts. Once inside, Neorickettsia can infect macrophages and other cell types. For some vertebrate species (e.g. dogs, horses and humans), neorickettsial infections cause severe disease. With a few exceptions, studies of Neorickettsia have …

A Surveillance Study On Tick And Tick-Borne Pathogen Diversity In Shimba Hills National Reserve, Kenya, Micky Mwamuye Mwananje

All Master’s Theses

Outbreaks of emerging and re-emerging tick-borne pathogens are becoming more frequent worldwide. Surveillance is critical to improve our understanding of pathogen diversity and their tick vectors. This will elucidate disease transmission dynamics that can inform the development of better disease prevention and control strategies. A total of 4,324 questing ticks (209 adult ticks, 586 nymphs and 3,502 larvae) were collected from six sites in Kenya‟s Shimba Hills National Reserve (SHNR). Morphologically, adults were identified to species level while nymphs and larvae were identified to the genus level. Three species from two genera of the Ixodidae family were identified; Amblyomma eburneum, …

Phylogeny And Antibiotic Activity Of Xenorhabdus Spp. Isolated From Nematode Symbionts In Kenya, Ryan M. Awori

All Master’s Theses

Xenorhabdus is a bacteria genus of the family Enterobacteriaceae. Bacteria of this genus form a mutualistic relationship with Steinernema entomopathogenic nematodes. More so, their antimicrobial production serves as a potential source of novel antibiotics in the wake of growing antimicrobial resistance. This study aimed to establish the phylogenetic relationship of three Xenorhabdus isolates to the 24 described species of the genus based on the 16s rRNA gene. Secondly, it aimed to determine the antibiotic activity of the three Xenorhabdus isolates from Kenya. Six 16s rRNA sequences were isolated in this study while 184 sequences were obtained from public databases compiling …

Trial Of Short-Course Antimicrobial Therapy For Intraabdominal Infection, J E. Mazuski, Et Al

Open Access Publications

No abstract provided.

Adenovirus Vector Expressing Stx1/Stx2-Neutralizing Agent Protects Piglets Infected With Escherichia Coli O157: H7 Against Fatal Systemic Intoxication, Abhineet S. Sheoran, Igor P. Dmitriev, Elena A. Kashentseva, Ocean Cohen, Jean Mukherjee, Michelle Debatis, Jonathan Schearer, Jacqueline M. Tremblay, Gillian Beamer, David T. Curiel, Charles B. Shoemaker, Saul Tzipori

Open Access Publications

No abstract provided.

Trends In Opioid Analgesic Abuse And Mortality In The United States, Richard C. Dart, Hilary L. Surratt, Theodore J. Cicero, Mark W. Parrino, S Geoff Severtson, Becki Bucher-Bartelson, Jody L. Green

Open Access Publications

No abstract provided.

Phenotypic Complementation Of Genetic Immunodeficiency By Chronic Herpesvirus Infection, Donna A. Macduff, Tiffany A. Reese, Jacqueline M. Kimmey, Leslie A. Weiss, Christina Song, Xin Zhang, Amal Kambal, Erning Duan, Javier A. Carrero, Marco Colonna, Brian T. Edelson, L David Sibley, Christina L. Stallings, Herbert W. Virgin, Et Al

Open Access Publications

No abstract provided.

Comparison Of Chromogenic Media For Recovery Of Carbapenemase-Producing Enterobacteriaceae (Cpe) And Evaluation Of Cpe Prevalence At A Tertiary Care Academic Medical Center, Morgan A. Pence, Tiffany Hink, Carey-Ann D. Burnham

Open Access Publications

No abstract provided.

Scratching The Surface – Tobacco-Induced Bacterial Biofilms, Justin A. Hutcherson, David A. Scott, Juhi Bagaitkar

Open Access Publications

No abstract provided.

The Nsp1, Nsp13, And M Proteins Contribute To The Hepatotropism Of Murine Coronavirus Jhm.Wu, Rong Zhang, Yize Li, Timothy J. Cowley, Adam D. Steinbrenner, Judith M. Phillips, Boyd L. Yount, Ralph S. Baric, Susan R. Weiss

Open Access Publications

No abstract provided.

Ebola Virus Vp35 Interaction With Dynein Lc8 Regulates Viral Rna Synthesis, Priya Luthra, David S. Jordan, Daisy W. Leung, Gaya K. Amarasinghe, Christopher F. Basler

Open Access Publications

No abstract provided.

Travel Advice For The Immunocompromised Traveler: Prophylaxis, Vaccination, And Other Preventive Measures, Rupa R. Patel, Stephen Y. Liang, Pooja Koolwal, Frederick Matthew Kuhlmann

Open Access Publications

No abstract provided.

Role Of Copper Efflux In Pneumococcal Pathogenesis And Resistance To Macrophage-Mediated Immune Clearance, Michael D L Johnson, Thomas E. Kehl-Fie, Roger Klein, Jacqueline Kelly, Corinna Burnham, Beth Mann, Jason W. Rosch

Open Access Publications

No abstract provided.

Subinhibitory Antibiotic Therapy Alters Recurrent Urinary Tract Infection Pathogenesis Through Modulation Of Bacterial Virulence And Host Immunity, Lee W. Goneau, Thomas J. Hannan, Roderick A. Macphee, Drew J. Schwartz, Jean M. Macklaim, Gregory B. Gloor, Hassan Razvi, Gregor Reid, Scott J. Hultgren, Jeremy P. Burton

Open Access Publications

No abstract provided.

Characterization Of Herpes Simplex Virus 2 Primary Microrna Transcript Regulation, Shuang Tang, Marta Bosch-Marce, Amita Patel, Todd P. Margolis, Philip R. Krause

Open Access Publications

No abstract provided.

Complete Genome Sequences Of Two Helicobacter Pylori Strains From A Canadian Arctic Aboriginal Community, Dangeruta Kersulyte, M. Teresita Bertoli, Sravya Tamma, Monika Keelan, Rachel Munday, Janis Geary, Sander Veldhuyzen Van Zanten, Karen J. Goodman, Douglas E. Berg

Open Access Publications

No abstract provided.

Dengue Hemorrhagic Fever Complicated By Intercostal Artery Hemorrhage., Syed Ahsan Ali, Sara Ahmed, Mehmood Riaz

Department of Medicine

Hemorrhagic manifestations are fairly common in Dengue hemorrhagic fever and are associated with increased mortality. During last few decades there have been increasing reports of Dengue infection with unusual manifestations. Here we present a case of dengue hemorrhagic fever complicated by spontaneous rupture of an intercostal artery leading to a large hematoma which was treated successfully with angio-embolization. To the authors' knowledge this is a first case of dengue hemorrhagic fever complicated by spontaneous intercostal artery hemorrhage.

Efficacy And Resistance Potential Of Jpc-3210 In Plasmodium Falciparum, Siobhan Marie Flaherty

USF Tampa Graduate Theses and Dissertations

Combating drug resistant malaria has been historically challenging, and remains so today. Recent reports from Southeast Asia show that Plasmodium falciparum is developing resistance to even our best defenses; artemisinin-based therapies. This development threatens to become a significant challenge in controlling malaria infections worldwide, making research into developing and characterizing new antimalarial drugs increasingly important. The purpose of this study was to characterize the resistance potential of novel antimalarial compound JPC-3210 in vitro using P. falciparum clones. JPC-3210 is a new long acting drug with potential to be used in combination with fast-acting drugs like artemisinins to cure drug resistant …