Life Sciences Commons^™

Repurposing Lansoprazole And Posaconazole To Treat Leishmaniasis: Integration Of In Vitro Testing, Pharmacological Corroboration, And Mechanisms Of Action, Yash Gupta, Steven Goicoechea, Jesus G. Romero, Raman Mathur, Thomas R. Caulfield, Daniel P. Becker, Ravi Durvasula, Prakasha Kempaiah

Chemistry: Faculty Publications and Other Works

Leishmaniasis remains a serious public health problem in many tropical regions of the world. Among neglected tropical diseases, the mortality rate of leishmaniasis is second only to malaria. All currently approved therapeutics have toxic side effects and face rapidly increasing resistance. To identify existing drugs with antileishmanial activity and predict the mechanism of action, we designed a drug-discovery pipeline utilizing both in-silico and in-vitro methods. First, we screened compounds from the Selleckchem Bio-Active Compound Library containing ~1622 FDA-approved drugs and narrowed these down to 96 candidates based on data mining for possible anti-parasitic properties. Next, we completed preliminary in-vitro testing …

Comparative Studies On Biochemical And Pharmacological Profiles Of Unfractionated Heparins & Their Depolymerized Derivatives From Bovine, Ovine And Porcine Origins, Ahmed Kouta

Dissertations

Heparin and heparin related drugs have remained the anticoagulant of choice for medical and surgical indications. These drugs are comprised of poly-component sulfated chains of varying length and biophysical structure with direct and indirect pharmacological effects. Heparins produce their therapeutic effects by multiple mechanisms involving both the cellular and humoral targets. These drugs represent natural products which are isolated from mammalian tissue rich in mast cells. Currently used heparin and LMWHs are obtained from porcine mucosal tissue. Other animal sources including bovine and ovine tissues also provide additional sources for the manufacturing of heparins. While there may be microchemical and …

Cardioprotective Extracellular Vesicles Derived-Micrornas: Sorting Mechanisms And Functions, Anh P. Phan

Dissertations

Extracellular vesicles (EVs) are nano-size membrane bound vesicles that are derived from the fusion of multivesicular endosomes with the plasma membranes. EVs have important roles in intercellular communication through the transfer of their unique cargoes including RNA, DNA and protein molecules to recipient cells. Mesenchymal stem cell (MSC)-derived EVs have been shown to reduce infarct size and reduce the progress of heart failure after cardiac ischemia/reperfusion (I/R) injury in animal models. Small non-coding RNAs such as microRNA (miRNA) have been indicated as one of the active components that mediate the beneficial effects of MSC-derived EVs. However, the selective packaging mechanisms …

Reducing Reperfusion Injury In An Adult Rat Stroke Model With St-115 Treatment, Morgan Rae Lenz

Master's Theses

The restoration of blood flow to ischemic cerebral tissue can result in reperfusion injury, and blocking reperfusion injury can significantly aid in recovery of ischemic tissue. Bradykinin has been shown to exhibit protective effects, but does not reach protective levels during reperfusion due to inactivation by aminopeptidase P2 (APP2). Therefore, inhibiting APP2 during reperfusion is a potential therapeutic strategy to aid in the reduction of reperfusion injury, leading to the development of ST-115, an APP2 inhibitor. It was hypothesized that administration of ST-115 during ischemic stroke, and just prior to reperfusion, will result in reduced neurological injury and increased functional …

Elucidation Of The Molecular Mechanisms Of Electrically-Induced Cardioprotection, Anne Elizabeth Roessler

Dissertations

Cardiovascular disease is the leading cause of death worldwide. A myocardial infarction (MI), commonly known as a heart attack, is a major event in cardiovascular disease characterized by reduced blood flow to the heart. The ischemia and reperfusion (I/R) injury associated with an MI results in a region of dead tissue in the heart called an infarct, the size of which influences patient prognosis. In the 1980s, it was discovered that short, non-lethal episodes of I/R, termed ischemic preconditioning (IPC), can protect the heart against a subsequent MI. Ischemic preconditioning demonstrated the phenomenon of endogenous cardioprotection. Cardioprotection has great potential …

Addressing Environmental Gentrification: Improving Environmental Health For Children And Youth Without Displacement, Tania Schusler, Amy Krings

Social Work: School of Social Work Faculty Publications and Other Works

Historically, low income communities and communities of color have borne the brunt of environmental pollution with limited access to environmental amenities. This has arisen, in part, due to marginalized communities’ lack of access and influence in environmental decision making, as well as legacies of racial and ethnic housing segregation (Cole & Foster, 2001). Environmental justice concerns include the disproportionate placement and inequitable regulation of polluting facilities in areas populated by people who are poor and/or racial minorities (Bryant, 1995: Bullard, 1993; Mohai & Bryant, 1992; Lavelle & Coyle, 1992). The inequitable distribution of environmental pollution is especially problematic for children’s …

Studying The Antagonistic Relationship Between Nkg2d And Tgf-Β Signaling In Cd8+ T Cells, Kushal Prajapati

Dissertations

Despite the remarkable success of cancer immunotherapies in treating patients with hematological cancers, the clinical response rates of immunotherapies in the case of solid tumors have been dismal. One major reason for the lower response rates is tumor-induced immune-suppression mediated by TGF-?, which directly suppresses the functionality of CD8+ T cells by inhibiting their activation, proliferation, and acquisition of inflammatory cytokines, granzyme B and perforin. On the other hand, NKG2D, a potent co-stimulatory receptor, has effects on CD8+ T cells opposite to that of TGF-?. In T cells from 22 healthy human donors, we found that the suppression by TGF-? …

Chronic Toxicity Of Binary‐Metal Mixtures Of Cadmium And Zinc To Daphnia Magna, Edgar Pérez, Tham C. Hoang

School of Environmental Sustainability: Faculty Publications and Other Works

The present study characterized the chronic effect of binary‐metal mixtures of cadmium (Cd) and zinc (Zn) on Daphnia magna. The titration design was chosen to characterize the 21‐d chronic effects of the binary‐metal mixtures on survival, growth, reproduction, and metal accumulation in D. magna. Using this design, increasing concentrations of Zn (10, 20, 40, 80, 120, 160, and 200 μg/L) were titrated against a constant concentration of 1.5 μg/L Cd. The results demonstrated that Cd was highly toxic to D. magna. In a mixture with Cd and Zn, sublethal concentrations of 10 and 20 μg/L Zn were …

Characterization Of The Effect Of Aeration On A Commercially Available Fibrin Sealant For Use In Wound Therapy, Adam Robert Marek

Dissertations

Wound care affects millions of people worldwide each year, and the need for an effective wound therapy still exists. The aim of this study was to characterize a novel, aerated biopolymer, fibrin foam, which is generated through a patented mixing process using a commercially-available fibrin sealant. This research developed a distinct preparation of fibrin foam that creates a porous environment with improved wound healing properties. With this fibrin foam, characterization assessments were performed, including evaluation of mixing parameters, biocompatibility, and biomechanical strengths.

Fibrin foam is created by performing six passes through a mixing device, which generates a foam matrix with …

Chronic Effects Of Lead Exposure On Atherinops Affinis (Topsmelt): Influence Of Salinity And Organism Age, Erik Joseph Reynolds

Master's Theses

Pb (lead) appears in the environment as a consequence of both natural and anthropogenic processes. Mining, smelting, coal burning, lead acid batteries, and cement manufacturing substantially release Pb into aquatic environments. The goal of this study was to determine the influence of salinity and organism age on chronic toxicity of Pb to Atherinops affinis (topsmelt) in support of development of a species sensitivity distribution (SSD). Species sensitivity distributions assist in ecological risk assessments and establishing quality criteria for contaminants. Three chronic exposure studies were conducted for 28 days in a water flow-through testing system. Survival, standard length, dry weight, and …

Examining The Regulation Of Kv7 K+ Channels In Airway Smooth Muscle Cells And Their Potential As Novel Therapeutic Targets For The Treatment Of Asthma, Jennifer Haick

Dissertations

Asthma is a disease characterized by nonspecific and exaggerated airway narrowing, termed airway hyperresponsiveness (AHR), which involves the excessive contraction of airway smooth muscle. Despite the fact that airway smooth muscle is widely studied and understood to play a role in AHR, little is known about the specifics of that role. Our laboratory recently found that Kv7 potassium (K+) channels are expressed in airway smooth muscle cells (ASMCs). Kv7 channels are voltage sensitive K+ channels whose outward flux of K+ ions promotes a negative resting membrane voltage in excitable cells, thereby opposing electrical excitability. Inhibition of K+ channels is known …

Phosphodiesterase Inhibition As A Mechanism Of Ion Channel Modulation By Celecoxib, Christina Jean Robakowski

Master's Theses

The overall objective of this thesis work is to determine the mechanism by which celecoxib modulates Kv7 potassium channels in vascular smooth muscle cells. The central hypothesis of the project is that celecoxib modulates Kv7 potassium channels in vascular smooth muscle cells through inhibition of phosphodiesterase 4 (PDE4, which catalyzes the breakdown of cyclic adenosine monophosphate (cAMP)), thereby activating a cAMP/protein kinase A (PKA) signaling pathway. The aims of this thesis targeted different points in the cAMP/PKA pathway with pharmacological interventions using whole cell perforated patch clamp electrophysiology and biochemical methods.

The data suggest multiple mechanisms by which celecoxib could …

Effects Of Contaminated St. Lucie River Saltwater Sediments On An Amphipod (Ampelisca Abdita) And A Hard-Shell Clam (Mercenaria Mercenaria), Tham C. Hoang, Gary M. Rand

School of Environmental Sustainability: Faculty Publications and Other Works

The St. Lucie estuary (SLE) ecosystem in South Florida has been shown to be contaminated with metals and pesticides. Our earlier studies also showed that aquatic organisms, especially benthic species in the SLE ecosystem, might be potentially at high risk from copper (Cu) exposure. The objectives of this study were to conduct studies with separate groups of organisms exposed to seven field-collected sediment samples from the St. Lucie River according to standard procedures to evaluate toxicity and tissue concentrations of Cu and zinc (Zn). Short term and longer term whole sediment acute toxicity studies were performed with Ampelisca abdita and …

Non-Additive Toxicity Of Bi-Metal Mixtures To Fathead Minnows, Natalie Rae Lynch

Master's Theses

Much research has been conducted to assess the toxicity of metals to aquatic organisms. Most of the research has focused on the toxicity of individual metals. Recently, attention has been paid to metal mixture toxicity because metals are usually present as mixtures in contaminated environments. The literature review indicates that metal mixtures may be additive, synergistic, or antagonistic to freshwater species. However, the data is not consistent and is dependent on the metal and organisms. The goal of this research is to use a systematic experimental design to characterize the toxicity of Cu, Zn, Cd and Ni mixtures to Pimephales …

Vascular Kv7 (Kcnq) Potassium Channels As Therapeutic Targets In Cerebral Vasospasm, Bharath Kumar Mani

Dissertations (6 month embargo)

Cerebral vasospasm, a grave sequel to subarachnoid hemorrhage (SAH), is characterized by prolonged severe constriction of arteries in the base of the brain, including the basilar artery. Spasmogens (serotonin, endothelin and vasopressin), elevated in response to SAH, induce persistent depolarization of the myocytes in the artery wall, leading to continuous influx of calcium (Ca2+) through voltage-sensitive Ca2+ channels (VSCC) resulting in hyperconstriction (spasm). The spasm of the arteries restricts blood flow to the brain, inducing ischemic neurological deficits and consequential high morbidity and mortality. The cellular pathogenesis of cerebral vasospasm is poorly understood and the therapeutic options are limited.

Kv7 …

Compositional Determinants Of The Pharmacological Actions Of Heparins, Angel Lee Gray-Shah

Dissertations

This dissertation primarily focuses on how differences in molecular weight (MW) and structural composition affect the pharmacological activity of heparin and its derivatives. Heparins are a mixture of glycosaminoglycans chains which are used to prevent thrombosis in a number of clinical indications. Heparins promote the inhibition of blood coagulation via their plasmatic cofactors antithrombin (AT) and heparin cofactor II (HCII).

In these studies, various heparins with molecular weights ranging from 2.6 to 16.5 kDa were investigated. Not only the molecular weight but also the oligosaccharide composition greatly varied in these agents. One of the major objectives of this research was …

Kv7 K+ Channels In Airway Smooth Muscle Cells As Target For Asthma Therapy, Priyanka Prakash Kakad

Master's Theses

Airway hyperresponsiveness (AHR) is an important etiological feature of asthma, the molecular mechanisms of which are poorly understood, thus preventing development of specific and effective therapies. We investigate the role played by Kv7 voltage-activated potassium channels in the pathophysiology of AHR and evaluate the significance of their regulation in treatment of asthma. Our studies provide the first evidence for expression of multiple Kv7 channels in guinea pig and human airways and demonstrate that the expression of Kv7 channels is reduced in allergen-sensitized guinea pig airways. Our ex vivo functional studies reveal that clinically available Kv7 channel activators attenuate the bronchoconstrictor …

Gabab Regulation Of Methamphetamine-Induced Associative Learning, Robin Michelle Voigt

Dissertations

Addiction is a chronic, relapsing disorder for which strikingly few effective therapies exist, and there are no FDA-approved pharmacotherapies for methamphetamine (Meth) addition. There is an immense need to identify the neurobiological underpinnings of psychostimulant addiction and develop efficacious drug therapies to compliment the current mainstay treatment of behavioral/cognitive therapy.

Re-exposure to cues associated with psychostimulants (e.g., drug paraphernalia) increase neuronal activity and can elicit drug-craving and -seeking; an effect which is profound and long-lasting. A mechanism to disrupt those brain processes which are necessary to maintain the association may reduce the incidence of cue-elicited relapse.

Conditioned place preference (CPP) …

Corticosteroid Modulation Of Hippocampal Neural Activity, Dayne Y. Okuhara

Dissertations

No abstract provided.

Characterization Of Adaptive Changes In 5-Htia Receptor Systems Induced By Repeated Injections Of 5-Ht Uptake Inhibitors, Qian Li

Dissertations

No abstract provided.

Amyloid-β Deposition In Rat Brain: Histopathological And Functional Sequelae, Einar M. Sigurdsson

Dissertations

No abstract provided.

Effect Of Af64a On Rat Brain Septo-Hippocampal And Striatal Cholinergic Systems: A Neurochemical And Molecular Analysis, Qing Ivy Fan

Dissertations

No abstract provided.

Characterization Of Central Serotonergic Alterations In Male Rats Following Prenatal Exposure To Fluoxetine, Theresa M. Cabrera

Dissertations

No abstract provided.

Androgen Receptors In The Hippocampus: Localization, Autoregulation, And Modulation Of Gene Expression In The Adult Male Rat, Janice E. Kerr

Dissertations

No abstract provided.

Relationships Between The Expression Of Genes Involved In The Regulation Of Apoptosis And Cell Death Induced By Nitrogen Mustard In Human Colon Carcinoma Cell Lines, Greggory Bernard Herbert

Dissertations

No abstract provided.

Pharmacologic Studies On Synthetic Analogues Of Heparin With Selective Affinity To Endogenous Serine Protease Inhibitors, Walter P. Jeske

Dissertations

No abstract provided.

Comparative Pharmacologic Studies On Synthetic And Recombinant Inhibitors Of Thrombin, Demetra D. Callas

Dissertations

No abstract provided.

Dopaminergic Modulation Of Basal Forebrain Cholinergic Neurons, Mary Elizabeth Muench

Master's Theses

No abstract provided.

The Interaction Of O6-Benzylguanine And Streptozotocin In The Inactivation Of O6-Methylguanine Dna Methyltransferase And The Reversal Of 1,3 Bis (2-Chloroethyl)-1-Nitrosourea Resistance, Upendra Kumar Marathi

Master's Theses

No abstract provided.

Central Serotonergic Stimulation Of Renin Secretion, Peter Andrew Rittenhouse

Dissertations

No abstract provided.