Pharmacology, Toxicology and Environmental Health Commons^™

Urinary Excretion Of (1-3)-Beta-D-Glucans., Debra K. Head

Electronic Theses and Dissertations

(1→3)-β-D-Glucans are carbohydrate polymers that are present in the cell wall of various fungi and bacteria; they are pathogen associated molecular patterns that circulate during infection and modulate immunity. Our laboratory has previously established the pharmacokinetics of intravenously and orally administered glucans; the present studies investigated the renal excretion of (1→3)-β-D-glucans following intravenous and oral administration. Three fluorescently-labeled glucans were administered to adult male rats in the presence or absence of toxic challenge. Urine specimens were collected and analyzed by fluorescence spectroscopy, size-exclusion chromatography and GPC/MALLS. 71 ± 3% of fluorescence remained in the >5K MWCO fraction; this fraction showed …

Maturational Changes In Myosin Light Chain Kinase Activity In Ovine Carotids, Elisha Raju Injeti

Loma Linda University Electronic Theses, Dissertations & Projects

Vascular reactivity changes dramatically during postnatal maturation due in large part to developmental changes in myofilament calcium sensitivity. Recent findings suggest that reactivity of the thick filament component of calcium sensitivity is upregulated in fetal compared to adult arteries. In light of these findings, the present study tests the hypothesis that upregulation of fetal thick filament reactivity is due to upregulation of myosin light chain kinase (MLCK) activity. To test this hypothesis, MLCK abundance and its activity is measured in intact arteries. The results indicate that MLCK abundance is 6.03 ± 0.96 fold greater in adult than in fetal arteries. …

Nanoengineered Templates For Controlled Delivery Of Bioactive Compounds, Nalinkanth Ghone Veerabadran

Doctoral Dissertations

The significance of any drugs, therapeutic proteins, or any bioactive compounds, is based not only on their effects on diseases but also on how specifically, how readily, how controllable and how prolonged their effects on the disease without having any side effects. Thus the techniques involved in the drug encapsulation and its controlled release for a longer duration of time form one of the important processes of drug reformulation. In recent years nanoparticles have created overwhelming attention for delivering drugs by nanoencapsulation. The smaller size of nanoparticles has longer circulation time and higher cellular uptake when compared with larger size …

Use Of Monoclonal ∆-9-Tetrahydrocannabinol Antibodies Chemically Bound To A Polystyrene Surface Using Glutaraldehyde For The Purpose Of Extracting ∆-9-Tetrahydrocannabinol And ∆-9-Tetrahydrocannabinol Carboxylic Acid From Postmortem Whole Blood Samples For Analysis By Gas Chromatography Mass Spectrometry, Thomas Sidney Pittman

Dissertations

Quantitations of drugs and their respective metabolites in postmortem blood samples using gas chromatographic instrumentation is a primary analytical practice used to determine if drugs played a role in or were the cause of a victim's death. Postmortem blood samples often prove difficult to work with due to interfering substances formed during the putrefaction process. Attempts to eliminate interfering substances with present day extraction methods can be time-consuming, costly and often ineffective when dealing with drugs that exhibit toxicity or impairment at very low concentrations. This study was conducted using monoclonal antibodies chemically bound to a polystyrene surface to extract …

Cannabinoids: A Novel Treatment Strategy For Retinal Neurodegenerative Disorders, Sandeep Samudre

Theses and Dissertations in Biomedical Sciences

Synthetic and naturally occurring cannabinoids are known to decrease intraocular pressure (IOP). Glaucomatous damage to the retina and optic nerve progresses even after therapy to maintain normal intraocular pressure (IOP). Topical application of cannabinoids decreases IOP while not affecting blood pressure or heart rate. Based upon their effects on other tissues, we hypothesize that these analogs reduce IOP and may also confer direct neuroprotective effects on the retina, possibly via CB1 and/or CB2 receptors. The purpose of this study is to determine if the newly synthesized CB agonists, lipid soluble O-1812 (CB 1), and water soluble O-2545 (CB 1

The …

Three Models Of Anthrax Toxin Effects On The Map-Kinase Pathway And Macrophage Survival, Daniel J. Schneider

Theses and Dissertations

Lethal factor (LF), a component of anthrax toxin, is the primary virulence factor that allows Bacillus anthracis to evade the immune response by blocking the activation of mitogen-activated protein kinase (MAPK) enzymes. This research modifies three published MAPK models to reflect this signal inhibition and to estimate a first-order reaction rate by fitting the models to published viability data for two macrophage cell lines cultured with the LF-producing Bacillus anthracis-Vollum1B strain. One model appears to be ill-suited for this purpose because not all relevant MAPK components could be integrated into the inhibition equations. Despite different underlying parameters and values, the …

Characterization Of A Fluorescent Protein Reporter System, Sandra J. Dias

Theses and Dissertations

Chemical and biological threats are ever present and attacks have occurred throughout the world in both war and peace-time. Multiple government agencies, academia, and private industry are developing detection capabilities to address such threats. The research presented in this paper supports development of a modular synthetic biology based system that detects and reports the presence of a threat agent. Synthetic biology builds upon past research in genetic engineering and seeks to combine broad applications within biotechnology in novel ways. This basic research project will help to demonstrate a proof-of-concept design which will guide future studies on the development of a …

In Vitro Toxicity Of Aluminum Nanoparticles In Human Keratinocytes, Stephanie Mccormack-Brown

Theses and Dissertations

Nanotechnology promises to be the defining technology of the 21st century. At an annual investment of $1B, it provides significant contributions to manufacturing, medicine, energy conservation, and the environment. Nanoparticles are structures with at least one dimension in the 1 to 100 nanometer (nm) range. DoD and US Air Force interest in aluminum nanoparticles (AL NPs) stems from its ability to enhance combustion jet fuel, thus increasing fuel efficiency. The addition of AL NPs to JP-8 may pose a unique dermal hazard to aircraft maintenance workers. There is no published data on AL NP toxicity effects on human skin. This …

In Vitro Toxicity And Inflammation Response Induced By Copper Nanoparticles In Rat Alveolar Macrophages, Brian M. Clarke

Theses and Dissertations

Nanotechnology is a thriving industry and has the potential to benefit society in numerous ways. However, not all environmental and human health concerns of nanomaterials have been addressed. Thus, the purpose of this research was to investigate the toxicity and inflammation potential (using cytokines TNF-alpha and IL-6 as indicators) of various sized copper nanoparticles (40, 60, and 80 nm) in rat alveolar macrophages. Toxicity measurements were accomplished by means of in vitro techniques and toxicity mechanisms were studied by measuring reactive oxygen species (ROS) production. In addition, cytokine measurements used enzyme-linked immunosorbent assay (ELISA) methods. Results show copper nanoparticles as …

Optimization Of Therapeutic Strategies For Organophosphate Poisoning, Gregory G. Seaman

Theses and Dissertations

The National Preparedness Vision requires the U.S. be prepared to prevent, protect against, respond to, and recover from all hazards associated with a chemical attack. Results of this study demonstrate that we cannot protect service members and first responders as required following a nerve agent attack. The research presented herein aimed to construct a physiologically based pharmacokinetic model to determine optimal therapeutic strategies for organophosphate (nerve agent) poisoning. The constructed model integrated organophosphates and two antidotes, atropine and oximes. Model results reasonably mirrored literature data and anecdotal observations of organophosphate poisoning. Results suggest a symptoms-based dosing strategy of atropine and …

Factors That Influence The Distribution Of Antibiotic Resistant Bacteria In The Mud River, Wv, Timothy Shaun Dotson

Theses, Dissertations and Capstones

Background: Prior studies of the Ohio and Mud Rivers have shown that fecal contamination alone does not explain the distribution of antibiotic resistant bacteria (ARB) in surface waters. The objectives of this study were to determine effects on the distribution of ARB in the Mud.

Methods: Water samples and physical parameters were collected twice per season in spring through fall at 12 sites on the Mud River. Aliquots were plated on R2A agar and R2A agar plus individual antibiotics for the enumeration of total cultivable bacteria, and cultivable bacteria resistant to ciprofloxacin, virginiamycin, or tetracycline respectively. The IDEXX Quanti-Tray/2000™ method …

The Metastasis Suppressor Nm23-H1 Is Required For Dna Repair, Mengmeng Yang

University of Kentucky Doctoral Dissertations

NM23-H1 represents the first identified metastasis suppressor, exhibiting reduced expression in breast carcinoma and melanoma, and an ability to inhibit metastatic growth without significant impact on the transformed phenotype. Although its molecular mechanism of action is not fully understood, NM23-H1 possesses at least three enzymatic activities that may mediate metastasis suppressor function. It catalyzes nucleoside diphosphate kinase (NDPK) activity, as well as protein histidine kinase and 3’-5’ exonuclease activities. As 3’-5’ exonucleases are generally required for maintenance of genomic integrity, this activity represents a plausible mediator to underlie the metastasis suppressor function of NM23-H1 protein. To investigate the relevant activity …

The Evaluation Of Midazolam On Head Injured Patients In The Prehospital Setting, Dragana Klinac

Theses: Doctorates and Masters

Midazolam (Hypnovel ®) is the only sedating agent used by paramedics at St John Ambulance Service W.A. in the management of many conditions including seizure activities, antisocial or uncontrollable behaviours, back pain incidents and head injuries. Midazolam, with a rapid absorption, fast onset of action and short duration on neurological activity, has been accepted as a safe and effective agent in prehospital treatment since the late-1990s. Often, if a patient is not complying with treatment or is uncontrollable or aggressive, paramedics are required to sedate the individual. This study primarily examines the use of midazolam for the sedation of unmanageable …