Biomedical Engineering and Bioengineering Commons^™

Detecting Physiological Concentrations Of Alzheimer’S Associated Amyloid-Β Protein Utilizing A Cell-Based Response, Brittany Elizabeth Watson

Theses and Dissertations

Alzheimer’s disease (AD) is characterized symptoms of cognitive impairment resulting from blood-brain barrier (BBB) breakdown and neuronal cell death. AD is associated with aggregated amyloid-β (Aβ) plaques deposited around brain vasculature and within the brain. Changes in the brain occur up to 20 years before symptoms arise; however, there is currently no pre-symptomatic detection method available for AD. An intact BBB requires tight junction proteins (TJs) that render relatively high transendothelial electrical resistance (TEER). AD-associated breakdown of the BBB correlates with vascular Aβ deposition, suggesting that aggregated, pathological Aβ can modulate TEER. We explore leveraging this cellular response for early …

Histomechanical Compatibility Of Coronary Artery Bypass Grafts, Colton J. Kostelnik

Theses and Dissertations

Coronary artery disease is a localized form of atherosclerosis that can severely restrict blood flow to the heart often requiring a surgical intervention known as coronary artery bypass grafting (CABG) to reestablish perfusion to this essential circulation. To some extent, the selection of the autograft tissue is at the surgeon’s discretion with factors such as stenosis location and the existing tissue’s pathological state contributing to a choice that could be deterministic in surgical outcomes. Many post-operative complications and premature graft failures originate from graft-target tissue incompatibilities and altered blood flow patterns. We hypothesize that mechanical mismatching between the graft material …

Investigating The Impact Of Endothelial Dysfunction And Aging On Vascular Remodeling Using Mouse Models, Liya Du

Theses and Dissertations

Endothelial dysfunction, characterized by a reduction in the bioavailability of nitric oxide (NO), is a major factor in the initiation and progression of atherosclerosis, an age-related chronic inflammatory process in the arterial wall and the leading cause of mortality and morbidity globally. A better understanding of alterations in vascular structure and function associated with endothelial dysfunction can facilitate the early detection of atherosclerosis and the development of potential pharmaceutical interventions. This study aims to clarify the impact of endothelial dysfunction in conjunction with aging on the microstructure of aortic extracellular matrix (ECM) and to elucidate the relationship between microstructural adaptation …

The Effect Of Pulsed Field Dc Electrophoresis And Field Amplified Sample Stacking On The Microchip Electrophoretic Separation Of Organic Dyes, Travis Geoffrey Stewart

Theses and Dissertations

The utility of field amplified sample stacking and pulsed field electrophoresis toward improving electrophoretic outcomes was studied with regards to the electrophoretic separation of three organic dyes rhodamine B, 2’,7’-dichlorofluorescein, and fluorescein salt in microchip electrophoresis conditions. In this study, there were four experimental groups: nonstacking nonpulsed, nonstacking pulsed, sample stacking nonpulsed, and sample stacking pulsed.

Electrophoretic outcomes were evaluated by examining the electrophoretic separations under an epifluoresence detection method, plotting the signal intensities vs. time, and comparing separation resolutions and signal-to-noise ratios between experimental groups. From this it was shown that sample stacking nonpulsed conditions yielded the best outcome …

Neurochemical, Molecular, And Behavioral Effects Of Intranasal Insulin, Jennifer Marie Erichsen

Theses and Dissertations

Age-related cognitive decline (ARCD) is one of the most dreaded aspects of growing old and a public health concern. Unfortunately, there is currently no treatment that effectively ameliorates ARCD. In recent decades, intranasal insulin (INI) has demonstrated promising memory enhancements for rodents and individuals with Alzheimer’s disease, both in basic science research laboratories and multi-center clinical trials. Other studies have shown INI improves memory and cognition in healthy rodents and humans, indicating that INI may hold promise as a successful ARCD therapeutic. However, there is a glaring lack of evidence regarding how INI produces these effects. The goal of these …

Long Non-Coding Rna Pvt1 – An Exploratory Study In Ovarian And Endometrial Cancer, Kevin Tabury

Theses and Dissertations

Gynecological cancers, ovarian and endometrial cancer, are still leading causes of cancer-related death in women worldwide. Early detection methods as well as treatment resistance remain a challenge. Long non-coding RNAs (lncRNAs) are emerging as therapeutic targets with diagnostic and prognostic potential with lncRNA PVT1 being one of them.

Here I test and demonstrate the role of PVT1 in ovarian cancer growth and metastasis. PVT1 is amplified and overexpressed in ovarian cancer and has predictive value for survival and response to targeted therapeutics. We find that expression of PVT1 is regulated by tumor cells in response to cellular stress, particularly loss …

The Submission Of A Section 513(G) Request For Information, Morgan Ashley Lano

Theses and Dissertations

The Food and Drug Administration designates all medical devices into one of three general classes contingent on their intended use, indications for use, and potential risk to the user. This classification dictates the further path the device must take to be approved for the commercial market. Section 513(g) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360c(g)) is submitted in order to gain the agency’s unofficial classification and suggested regulatory requirements. The Coagulation Companion (MicroVide) is a device designed to fluorescently quantify a key enzyme involved in the coagulation cascade, plasmin, in pediatric patients. clot formation and degradation …

The Immune Modulatory Role Of Endocannabinoid Anandamide To Suppress Inflammation Through Regulation Of Microrna And Microbiome, Muthanna Ali Sultan

Theses and Dissertations

Cannabinoids are group of compounds that exerts their anti-inflammatory action through activation of CB1 and CB2 receptors and other minor receptors. In the current study, we investigated the effect of Anandamide (AEA) on Acute Respiratory Distress Syndrome (ARDS) induced by exposure to Staphylococcus Enterotoxin B (SEB) intranasally. We found that C57BL/6 mice treated with AEA showed improvement in the clinical functions of the lungs, accompanied by a decrease in the infiltration of inflammatory cells in the lung tissue, and a decrease in the secretion of pro-inflammatory cytokines. Furthermore, AEA regulated the miRNA profile of the mononuclear cells in the lungs …

Regulation Of Inflammatory Processes By Tryptamine, Cannabidiol And 2,3,7,8-Tetrachlorodibenzo-P-Dioxin, Nicholas Dopkins

Theses and Dissertations

Host immunity is a complicated system of pro-inflammatory and anti-inflammatory processes that respond to exogenous and endogenous threats to regulate host physiology, inhibit carcinogenesis, and protect from infections. Sustained deviance from normal immunological function occurs due to a variety of factors both endogenous and exogenous, with some factors that can dysregulate host immunity including: genetics, microbiota composition, toxin exposure, age, gender, and smoking. The etiology of inflammatory disorders is both convoluted and complex due to the sheer number of facets regulating host immunity. To better contribute to understanding how immunological dysregulation occurs we focused on how three anti-inflammatory compounds (tryptamine, …

Anatomical Correlates Of Age-Related Basal Forebrain Dysfunction, Brandy Lynn Somera

Theses and Dissertations

The basal forebrain (BF) is comprised of several nuclei including the substantia innominata, medial septum, nucleus basalis and diagonal band of broca which are involved in cognitive functions including attention, motivation, and arousal. BF neurons are particularly vulnerable to dysfunction and degeneration in aged humans and, more dramatically, in diseases such as Alzheimer's disease (AD). Age-related BF dysfunction may reflect diminished afferent regulation as well as an altered local glial environment. Our lab has previously shown reduced orexin/hypocretin innervation of BF in aging, a phenomenon that may link afferent dysfunction with altered microglial homeostasis. There is little research examining these …

An In Vitro Approach To Vascular Therapeutic Testing, Shahd Ali Hasanain

Theses and Dissertations

Aortopathies refer to a broad class of pathological conditions affecting the aorta and are a major cause of morbidity and mortality in the US. Specifically, aortic aneurysms and aortic dissections have diverse etiologies that are initiated by alterations in the tissue’s extracellular-matrix (ECM) proteins, namely collagen and elastin, thereby predisposing the aortic wall to weaken and rupture. Pentagalloyl glucose (PGG) has recently emerged as a non-surgical treatment to reduce the risk of dissection or rupture. PGG is a known antioxidant and anti-inflammatory which has been shown to have ECM-restorative qualities that enhance collagen and elastin’s functional properties. Prior studies using …

Pseudomyxoma Peritonei Derived Cancers: A Novel Study On Growth And Growth Suppression Utilizing Common Colorectal Cancer Agents, Raymond Kennith Bogdon

Theses and Dissertations

Pseudomyxoma peritonei is a devastating gastrointestinal disease characterized by the production of mucinous ascites within the peritoneal cavity. Historically, this condition is discovered in the advanced state due to the lack of adequate screening tests and typically presents as an enlarged abdomen and with symptoms of gastrointestinal distress. Treatment for this disease is a combination of cytoreductive surgery and heated intraperitoneal perfusion chemotherapy, but a successful operation does not guarantee full remission of this malignancy. This study focuses on 3 untested variants of PMP cancer, and 2 mucinous colorectal adenocarcinomas that had invaded into the peritoneal cavity. Clinical presentation of …

Mechanism Of Therapeutic Efficacy Of New Drugs In Glioblastoma, Firas Hameed Khathayer

Theses and Dissertations

Glioblastoma is the most malignant and prevalent brain tumor in adults. It can grow and spread quickly causing harm to brain health. The deregulation of epigenetic mechanisms is considered the main agent in the developing of GBM. One of the enzymes involved in epigenetic alternation and cancer development are histone deacetylases enzyme (HDAC) by removal acetyl group from histone and create condensed chromatin that suppresses transcription gene to histone and non-histone proteins involved in tumorigenesis. Histone deacetylase inhibitors (HADCi) are the most common therapeutic methods for many types of cancer treatments. In the present study, we used relative HDAC inhibitor …

Vascular Endothelial Dysfunction And Effects On Arterial Wall Microstructure, Jeffrey Thomas Rodgers

Theses and Dissertations

Vascular endothelial cell dysfunction (ECD) is a disease characterized by the inability of the vascular endothelial cells to transmit signaling molecules, namely nitric oxide (NO), in response to changes in blood flow rate. This disease is shown to be incident in the onset of more severe vascular disease such as hypertension, atherosclerosis, and heart failure. Long-term ECD is shown to cause long-term remodeling such as decreased flow-mediated dilation, increased pulse-wave velocity, intimal-medial thickening, and increased wall stiffness due to collagen deposition. We used second harmonic generation (SHG) microscopy to analyze this change in the collagen microstructure of the arterial extracellular …

Age And Sex Dependency Of Thoracic Aortic Aneurysm Progression In A Mouse Model Of Marfan Syndrome, Nazli Gharraee

Theses and Dissertations

Aneurysm of the ascending aorta is the most common type of thoracic aortic aneurysm, and it is a life-threatening manifestation of Marfan syndrome (MFS), a connective tissue disorder caused by mutation of the FBN1 gene. Incidence of Marfan syndrome is similar for men and women; however, men suffer from more severe aortic events compared to women.

This study aims to provide a better understanding of age and sex dependency of cell and extracellular matrix alterations of the aortic wall during the progression of the aneurysm caused by Marfan syndrome. To achieve this goal, the C1041G/+ mouse model of Marfan syndrome …

Defining The Pathophysiology Of Gut Humoral Immunodeficiency, Ahmed Dawood Mohammed

Theses and Dissertations

Mucosal antibodies maintain gut homeostasis by promoting spatial segregation between host tissues and luminal microbes. Antibody-deficiency is the most common form of primary immunodeficiency observed in humans. In antibody-deficient humans, abnormal composition of the gut microbiota ('dysbiosis') is associated with chronic inflammatory responses and gastrointestinal complications. However, the mechanisms by which dysbiosis promotes inflammatory disease are poorly defined. In the studies described in this dissertation, we utilize CD19-/- mice as a model of antibody deficiency to test the hypothesis that antibody deficiency negatively impacts gut physiology under steady-state conditions. Chapter #1 is an overview of B cell development and how …

A Comparative Study Of Cannabinoids & Cb1 Receptor Gi Signaling, Haley Kristen Andersen

Theses and Dissertations

The legalization of medical marijuana has highlighted cannabinoids as a potential, opioid-free therapeutic option for pain management; however, the rise in illicit synthetic cannabinoid-induced toxicity has demonstrated the need to outline cannabinoid molecular signaling. The cannabinoid-type 1 (CB1) receptor is an endogenous G protein-gated receptor (GPCR), well-expressed in the central nervous system (CNS) associated with modulating neuronal activity. Cannabinoid agonists bind to the CB1 receptor resulting in the inhibitory G protein (Gi) complex to dissociate into two subunits, Gβγi and Gαi. The Gαi subunit inhibits adenylyl cyclase, leading to a decrease in cyclic adenosine monophosphate (cAMP). The Gβγi subunit activates …

Cis-Resveratrol Upregulates Tyrosyl-Trna Synthetase And Inhibits The Proliferation Of Select Breast Cancer Cell Lines, Marion Cone Hope Iii

Theses and Dissertations

Breast cancer is one of the most commonly occurring cancers in women. 70% of breast cancer patients express ERα and are treated with tamoxifen (Tam), a drug that is used to directly target ERα. However, 20-30% of cancer patients develop a resistance to Tam. This resistance leads to a worse prognosis and other treatments such as DNA damaging drugs or radiation to eliminate these cells. Resveratrol (RSV) is a polyphenolic- compound found in plants such as grapes and hellebore and is known to evoke anti-cancer effects. While natural resveratrol exists as a mixture of both cis- and trans- isomers, so …

The Role Of Acute And Chronic Neuroinflammation In Depression: Uncovering The Relationship Between Histamine And Serotonin Transmission, Melinda Hersey

Theses and Dissertations

Depression is the leading cause of disability worldwide. Disorders of the brain, including depression, are notoriously difficult to treat because the basic pathology underlying behavioral outcomes remains undefined. Robust chemical biomarkers of these diseases have not been identified, nor are there reliable methods to measure brain chemicals. Depression is associated with chemical and inflammatory changes in the brain that are predicted to contribute to the pathology. By studying the serotonin and histamine systems we aim to better define the neurochemical basis of depression. Serotonin has long been hypothesized to play a role in depression since selective serotonin reuptake inhibitors (SSRIs) …

The Use Of Natural Anthraquinone Emodin As A Primary And Complementary Therapeutic In The Treatment Of Colorectal Cancer, Alexander-Jacques Theodore Sougiannis

Theses and Dissertations

5 Fluorouracil (5FU) chemotherapy is widely used in the treatment of colorectal cancer (CRC), and has been the first-choice chemotherapy drug for CRC for many years. However, nearly 10% of patients receiving chemotherapy die during the first 30 days of treatment. Further, it is estimated that 70% of surviving patients will develop non-specific toxicities as a result of chemotherapy treatment. We characterize these toxicities in an animal model of chemotherapy treatment and show that perturbations in the gut microbiome might be exacerbate the prolonged effects of chemotherapy. A compound that could attenuate the multiple non-selective toxicities associated with chemotherapy could …

Nitric Oxide Expression With Age And Diet In The Arterial Wall Of Apoe Knockout Mice, Kara Cooper

Theses and Dissertations

Background: Hypertension is a dangerous condition that precedes many cardiovascular events including myocardial infarction, stroke, transient cerebral ischemic attack and symptomatic aortoiliac occlusive disease. While it is universally accepted that arteries stiffen with age, the physiological reason for this is debated. In a previous study, by Dr. Shana Roach Watson it was shown that collagen fibers re-orient themselves in a circumferential direction, resulting in increased arterial stiffness. The study hypothesized that this collagen remodeling could be a result of decreased nitric oxide production.

Methods: This study measured nitric oxide in two different ways, indirectly via Immunoperoxidase staining for eNOS and …

Using Human Granulosa Cells To Select The Most Competent Embryos For Uterine Transfer In In Vitro Fertilization Cycles, Richard John Kordus

Theses and Dissertations

Infertility is a worldwide epidemic often treated with in vitro fertilization. The success of in vitro fertilization is directly dependent upon the quality of oocytes produced during the controlled stimulation of the patient’s ovaries. There is a need for improved methods to allow embryologists to select the most viable embryos with the highest probability of leading to live births since in vitro fertilization success is far from optimal.

Oocyte and subsequent embryo quality are intimately influenced by the granulosa cells which surround the oocyte during follicular maturation. The oocytes require proper signaling and energy production form the surrounding granulosa cells …

Effect Of Cannabinoid Treatment On Immune Cell Functions During Acute Lung Injury, Amira Kamil Mohammed

Theses and Dissertations

Staphylococcal enterotoxin B (SEB) is a highly potent CDC select agent that can trigger acute lung injury (ALI) via robust T cell proliferation and differentiation, and massive cytokine and chemokine release. Δ9-Tetrahydrocannabinol (THC) is a psychoactive ingredient found in Cannabis sativa. In the current study, we investigated the effects of treatment with THC on SEB-induced acute lung injury. To this end, acute lung injury was induced by a dual dose of SEB in C3H/HeJ mice, which were then treated with vehicle or THC. THC-treatment led to survival of all the SEB-administered mice when compared to vehicle-treated. This corroborated with THC-induced …

Advanced Geometric Analyses In Vascular Disease And Interventions, Dara Ahmadi Azar

Theses and Dissertations

The central function of the vascular system is the transportation and distribution of blood throughout the body. Occurrence of various forms of vascular disease, in which this central function is compromised, is associated with high mortality and morbidity rates. Vascular disease is an active and multifactorial process causing changes in local hemodynamics and blood vessel wall mechanics. The work presented here aims to advance the current knowledge on the role of local geometrical parameters in vascular disease and endovascular intervention modalities. In our first set of studies, we develop a computational framework to understand the role of aortic geometry in …

Adipose Tissue Engineering: A Therapeutic Strategy For The Treatment Of Obesity And Glucose Intolerance, Michael A. Hendley

Theses and Dissertations

Despite available treatment options, the number of people afflicted by type 2 diabetes has steadily risen for decades. Nearly 90% of the diabetic population also suffers from obesity and the link between the two diseases is undeniable. Characterized by rapid expansion of the adipose tissue and improper lipid storage, the mishandling of lipids by adipose tissue promotes the diabetic state. Excess lipids, unable to be properly stored, build up in peripheral tissues promoting insulin resistance and type 2 diabetes. Therapeutic strategies designed to address adipose tissue lipid handling could represent a promising treatment strategy for obesity associated type 2 diabetes. …

Experimental Methods And Techniques For Improved Biomechanical Characterization Of Diverse Murine Aortopathies, Brooks Alexander Lane

Theses and Dissertations

Aortopathies constitute a broad class of diseases affecting the aorta – the largest artery responsible for distributing oxygenated blood to the systemic circulation. Specifically, aortic aneurysms (AAs) are described as a focal dilation of the vascular wall exceeding 50% of the normal vessel diameter. Ultimately AAs may stabilize, dissect, or rupture, with the latter virtually ensuring mortality. Currently clinicians consider prophylactic intervention based on size and growth-rate criteria that have been estimated from large-cohort statistical analyses. These criteria, however, fail to address the underlying mechanisms. Furthermore, 13% of small-to-mid sized AAs have been found to rupture prior to meeting these …

Rage Expression And Inflammation In Alzheimer’S Disease: In Vitro Model Development And Investigation Of A Potential Peptoid Inhibitor, Lauren Michell Wolf

Theses and Dissertations

Despite the increasing prevalence of Alzheimer’s disease (AD), efforts to establish a definitive treatment or cure have met with little success. Many previous therapeutic strategies for AD have focused on the aggregation and accumulation of amyloid-b (Ab) in the brain, concentrating on its small intermediate aggregates as the primary targets to ameliorate neurotoxicity and damage. This approach has yielded little progress, and more recent discussions have shifted to strategies geared toward a multifaceted pathology, with chronic neuroinflammation emerging as an important factor in the disease etiology and progression.

The receptor for advanced glycation end-products, or RAGE, is …

Experimental Study Of Free-Solution Separation Under Pulsed Electrophoresis In Microchip, Xin Liu

Theses and Dissertations

Microchip electrophoresis (MCE) is a promising analytical tool started more than two decades. With the characteristics of short analysis time, trace level sample, high- throughput and easily integration, lots of efforts have been done with the transportation of the applications from capillary to microfabricated devices. However, with the complex designs on microchip rather than a single straight capillary channel, the strategies and approaches have to be figured out under the challenges of sample introduction, the improvement of separation conditions and the detection, for instance.

In miniaturized microchip, the separation channel is reduced to several centimeters or less, fast and quality …

Analysis Of Cellular Interactions Within A Collagen Hydrogel, Austin N. Worden

Theses and Dissertations

Evidence has arisen over the past several years that use of a three- dimensional (3D) culture system provides a distinct advantage over two- dimensional (2D) systems when cellular interactions are examined in a more natural environment. Changes in morphology, speed, and directionality of cells tested in both planar and 3D matrices have all demonstrated that using 3D system is advantageous. The changes to the cellular migration patterns were shown to be dependent on several variables within the surrounding substrate including cellular content, physical environment, and the matrix chemical milieu. We have taken advantage of using collagen hydrogels as a 3D …

An Anatomical Basis Of The Differential Cholinergic Modulation Of Valence-Specific Pyramidal Neurons In The Basolateral Amygdala, Nguyen Vu

Theses and Dissertations

Emotion is a crucial component of the decision-making process. The amygdala, known as the “orchestrator” of the emotion circuit, associates emotional valence with incoming sensory stimuli and thus contributes to decision- making. Within the basolateral nucleus of the amygdala (BLA), spatially segregated and genetically distinct pyramidal neurons (PNs) have been identified based on their correspondence to distinct behavioral stimuli. These PNs project to several brain regions mediating different aspects of the emotional spectrum.

For example, BLA PNs projecting to prelimbic (PL) and infralimbic (IL) cortex are involved in fear acquisition and fear extinction, respectively. However, the mechanism by which these …