Medicine and Health Sciences Commons^™

Bioerodible Calcium Sulfate Bone Grafting Substitutes With Tailored Drug Delivery Capabilities, Bryan R. Orellana

Theses and Dissertations--Biomedical Engineering

Bone regeneration or augmentation is often required prior to or concomitant with implant placement. With the limitations of many existing technologies, a biologically compatible synthetic bone grafting substitute that is osteogenic, bioerodible, and provides spacing-making functionality while acting as a drug delivery vehicle for bioactive molecules could provide an alternative to ‘gold standard’ techniques.

In the first part of this work, calcium sulfate (CS) space-making synthetic bone grafts with uniformly embedded poly(β-amino ester) (PBAE) biodegradable hydrogel particles was developed to allow controlled release of bioactive agents. The embedded gel particles’ influence on the physical and chemical characteristics of CS was …

Listeria Monocytogenes Can Utilize Both M Cell Transcytosis And Inla-Mediated Uptake To Cross The Epithelial Barrier Of The Intestine During An Oral Infection Model Of Listeriosis, Hilary Denney

Theses and Dissertations--Medical Sciences

The invasive pathways, InlA- and InB-mediated uptake and M cell transcytosis, that Listeria monocytogenes uses to invade the intestine have mainly been studied using infection models that do not truly replicate what occurs during a natural infection. Recently, our lab has developed an oral infection model that is more physiolocally relevant to what occurs during food borne listeriosis. We have sought to evaluate the relative roles of the previously defined invasive pathways, in our oral model of infection. We have done this by utilizing an InlAmCG Lm strain that is able to bind murine E-cadherin, knockout Lm strains, ΔinlA Lm …

Immobilizing Mutation In An Unconventional Myosin15a Affects Not Only The Structure Of Mechanosensory Stereocilia In The Inner Ear Hair Cells But Also Their Ionic Conductances, Diana Syam

Theses and Dissertations--Medical Sciences

In the inner and outer hair cells (OHCs) of the inner ear, an unconventional myosin 15a localizes at the tips of mechanosensory stereocilia and plays an important role in forming and maintaining their normal structure. A missense mutation makes the motor domain of myosin 15a dysfunctional and is responsible for the congenital deafness DFNB3 in humans and deafness and vestibular defects in Shaker-2 (Sh2) mouse model. All hair cells of homozygous Shaker-2 mice (Myo15^sh2/sh2) have abnormally short stereocilia, but, only stereocilia of Myo15^sh2/sh2OHCs start to degenerate after the first few days of postnatal development …

Phosphatidylinositol 3-Kinase (Pi3k) As A Therapeutic Target In Nsclc, Christopher W. Stamatkin

Theses and Dissertations--Pharmacy

Deregulated activation of phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies. The functions of this pathway are critical for normal cell metabolism, proliferation, and survival. In lung cancers, the PI3K pathway activity is often aberrantly driven by multiple mutations, including EGFR, KRAS, and PIK3CA. Molecules targeting the PI3K pathway are intensely investigated as potential anti-cancer agents. Although inhibitors of the pathway are currently in clinical trials, rational and targeted use of these compounds, alone or in combination, requires an understanding of isoform-specific activity in context. We sought to identify class IA PI3K enzyme (p110a/PIK3CA, p110b/PIK3CB, p110d/PIK3CD) activities using …

Expression And Splicing Of Alzheimer’S Disease Risk Gene Phosphatidylinositol-Binding Clathrin Assembly Protein, Ishita Parikh

Theses and Dissertations--Physiology

Recent Genome Wide Association Studies (GWAS) have identified a series of single nucleotide polymorphism (SNP)s that are associated with Alzheimer’s disease (AD). One of the SNPs, rs3851179 (G/A), is near the gene phosphatidylinositol-binding clathrin assembly protein (PICALM). To evaluate whether this SNP is associated with PICALM expression, we quantified PICALM mRNA in 56 brain cDNA samples. Using linear regression analysis, we analyzed PICALM expression relative to rs3851179, AD status, and cell type specific markers. An association was detected between rs3851179 and PICALM, microvessel mRNA, glial fibrillary acidic protein (GFAP) mRNA, and synaptophysin (SYN) mRNA. To gain clarity …

Anti-Müllerian Hormone In Stallions And Mares: Physiological Variations, Clinical Applications, And Molecular Aspects, Anthony N.J. Claes

Theses and Dissertations--Veterinary Science

Anti-Müllerian hormone (AMH) is a homodimeric glycoprotein that is best known for its role in regression of the Müllerian duct in the male fetus. Accumulating evidence indicates that AMH also has an important role during different physiological processes after birth. In contrast to other species, relatively little is known about AMH in the horse. In chapter one, developmental and seasonal changes in serum AMH concentrations in male horses were determined, and the use of AMH for determination of retained cryptorchid testes was established. In chapter two, the interrelationship between plasma AMH concentrations, antral follicle counts (AFC), and age in mares …

Science Classics, Mark Masthay

Chemistry Faculty Publications

An essay on the impact of the works in the Imprints and Impressions: Milestones in Human Progress, an exhibition of rare books from the collection of Stuart Rose. Exhibition was held Sept. 29-Nov. 9, 2014, at the University of Dayton.

Structure-Functional Prediction And Analysis Of Cancer Mutation Effects In Protein Kinases, Anshuman Dixit, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

A central goal of cancer research is to discover and characterize the functional effects of mutated genes that contribute to tumorigenesis. In this study, we provide a detailed structural classification and analysis of functional dynamics for members of protein kinase families that are known to harbor cancer mutations. We also present a systematic computational analysis that combines sequence and structure-based prediction models to characterize the effect of cancer mutations in protein kinases. We focus on the differential effects of activating point mutations that increase protein kinase activity and kinase-inactivating mutations that decrease activity. Mapping of cancer mutations onto the conformational …

Osteopathic Manipulative Medicine (Omm) And Reduction Of Nsaid Use In Low Back Pain: A Pilot Study, Kristopher Kelly

PCOM Biomedical Studies Student Scholarship

This randomized controlled pilot study is to determine if a combination of muscle energy and soft tissue techniques can reduce the amount of daily NSAID use in patients suffering from chronic non-specific low back pain (CNSLBP). Osteopathic manipulative treatment has been shown to be useful in treating low back pain. However, its role in reducing daily NSAID use in CNSLBP patients is unclear. This study was conducted at PCOM from January 2014 to April 2014. By design, patients were to be randomized into either a treatment group consisting of OMT or a control group consisting of a sham OMT. Of …

Chemopreventive Effects Of Pterostilbene In Metastatic Prostate Cancer Cells, Phillip A. Zook

PCOM Biomedical Studies Student Scholarship

Recent studies find that pterostilbene (PTS) exhibits more favorable drug properties and similar chemopreventive effects to its structural analogue resveratrol (RSV). However, few studies describe the activity of PTS in prostate cancer (PCa). Here, we conducted cell count experiments to assess the effects of PTS on metastatic PCa cell viability and to compare the potency of PTS to RSV in this respect. We also performed experiments to assess the effects of PTS on the androgen receptor (AR) and AR-mediated events. We used qPCR to measure the mRNA levels of the androgenresponsive gene (ARG), prostate-specific antigen (PSA), and Western blots to …

An Analysis Of Abnormal Electrocardiograms In First And Second Year Medical School Students, Molly Anne Kalish

PCOM Biomedical Studies Student Scholarship

The high stress level placed upon medical school students, particularly during their first and second didactic years, may have a negative effect on their health. Although surveys and subjective questionnaires have been used to evaluate the effects medical school has upon a student’s cardiovascular health, there has been little clinical data obtained to confirm this notion. The aim of this longitudinal study was to demonstrate whether any abnormal cardiovascular parameters, specifically QTc wave interval, cardiac axis vector and blood pressure abnormalities, could be documented to occur in two different classes of medical students during their first two years. Such information …

Effect Of Heme Oxygenase-1 On Matrix Metalloproteinase-3 Expression In Human Fibroblasts, Theresa A. Stangl

PCOM Biomedical Studies Student Scholarship

Heme oxygenase-1(HO-1) is an enzyme that plays a very important role in the resolution of inflammation. HO-1-based therapies are effective in a number of disease conditions. However, HO-1 also increases tumor growth, angiogenesis, metastasis and chemoresistance. Matrix metalloproteinase-3 (MMP-3) is an enzyme involved in physiological and pathophysiological tissue remodeling. Unbalanced expression of MMPs is a key feature of connective tissue destruction in chronic inflammatory conditions. Previously shown in this laboratory, the HO-1 inducer, hemin, increased MMP-3 mRNA expression in some HGF cultures. To assess whether HO-1 and/or its products regulate expression of MMP-3 in human fibroblasts, the effect of HO-1 …

The Effects Of Dihydrobiopterin And Tetrahydrobiopterin On Hydrogen Peroxide And Nitric Oxide Release During Extracorporeal Shockwave Lithotripsy (Eswl), Brittany Deiling

PCOM Biomedical Studies Student Scholarship

ESWL is an effective, non-invasive therapy utilized to fragment stones in the kidney and subsequently be cleared in the urinary tract. Although lithotripsy provides a safer alternative to invasive treatments for removing stones, ESWL may cause vasoconstriction after ESWL treatment, reducing renal blood flow, which can cause kidney damage leading to acute to chronic hypertension clinically. This may be due to kidney vascular endothelial dysfunction, which is characterized as increased oxidative stress and decreased endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) bioavailability. We hypothesized that ESWL would decrease NO and increase hydrogen peroxide (H₂O₂) in …

Liver Enzymes, Mean Platelet Volume, And Red Cell Distribution Width In Gestational Diabetes, Serpi̇l Erdoğan, Özhan Özdemi̇r, Halef Okan Doğan, Sevi̇lay Sezer, Cemal Reşat Atalay, Fatma Meri̇ç Yilmaz, Yüksel Koca

Turkish Journal of Medical Sciences

To investigate the value of measuring liver enzymes, red cell distribution width (RDW), and mean platelet volume (MPV) in predicting the development of gestational diabetes mellitus (GDM). Materials and methods: The medical records of all pregnant women followed by the obstetrics clinic between January 2010 and November 2012 were systematically evaluated, and patients with a diagnosis of GDM were identified. A total of 68 patients with GDM and 61 healthy controls were included in the study. Results of relevant laboratory parameters were recorded. Results: Out of all the parameters evaluated, mean values for platelet distribution width (PDW) and mean activities …

Detection Of Caga And Vaca Genotypes Of Helicobacter Pylori Isolates From A University Hospital In Ankara Region, Turkey, Ceren Erdoğdu, Zeynep Saribaş, Yakut Akyön Yilmaz

Turkish Journal of Medical Sciences

The cagA and vacA profiles and their association with clinical findings show a distinct geographical distribution. In the present study, we aimed to determine the cagA status and vacA allelic subtypes in strains isolated from a university hospital in Ankara and to evaluate their associations with histopathological and endoscopic findings. Materials and methods: A total of 120 H. pylori strains from stock cultures positive for the ureA gene were randomly included in the present study. Of these strains, cagA and vacA allelic subtypes (s1a, s1b, s2, m1, m2) were examined by polymerase chain reaction. Results: Of the 120 strains, 64 …

Diastolic Function Of The Right Ventricle Is Impaired In Experimental Type 2 Diabetic Rat Models, Ya Miao, Wei Zhang, Yuan Zhong, Ming Zhong, Xiao Ma

Turkish Journal of Medical Sciences

To evaluate diastolic function alterations of the right ventricle (RV) by echocardiography in type 2 diabetic rat models. Materials and methods: Male Wistar rats were divided into 2 groups: a control group (n = 8) and a diabetic group (n = 16, with 11 remaining at the end of the experiment), which was fed a high-fat and high-calorie diet and injected with streptozotocin (STZ). RV diastolic functional alteration of rat models was studied by the tricuspid flow Doppler (Ep, Ap, and Ep/Ap) and tissue Doppler imaging (TDI) (Em, Am, and Em/Am) of the lateral tricuspid annulus. RV structural alteration of …

Serotonin Receptor 2-Induced Mitochondrial Biogenesis As A Therapeutic Strategy For The Treatment Of Multiple Pathologies, Jennifer Linton Harmon

MUSC Theses and Dissertations

Mitochondrial dysfunction is a common pathophysiological feature in many acute and chronic organ injury states. Often, this mitochondrial dysfunction is sub-lethal and persistent and is a major contributor to loss of cellular function in the absence of cell death. Mitochondrial biogenesis (MB) is the process by which new mitochondria are created, and studies have demonstrated that pharmacological induction of MB can reverse loss of mitochondrial content, improve mitochondrial function and reduce measures of acute organ injury. Several classes of pharmacological agents that induce MB through divergent mechanisms have been identified. Previous studies demonstrated that 2,5-Dimethoxy-4-iodoamphetamine (DOI), a potent but non-specific …

The Involvement Of The Ca2+-Independent Phospholipase A2ss In The Pathogenesis Of Type 1 Diabetes, Robert N. Bone

All ETDs from UAB

chapters test the role of non-steady moisture or temperature on sex ratios produced by the

Mitochondrial Genetics Modify Body Composition, Metabolic Efficiency And Myocardial Metabolism, Kimberly Joanne Dunham-Snary

All ETDs from UAB

Obesity and cardiometabolic pathologies have reached epidemic levels worldwide over the last 30 years. Currently, the majority of research investigating possible genetic causes of obesity is focused on nuclear DNA (nDNA). While this has lead to the development of numerous animal models, it is apparent the etiology of obesity is more complex than single gene mutations. Recently it has also been suggested that mitochondrial DNA (mtDNA) mutations sustained during evolution as a consequence of our prehistoric environment may influence individual propensity and risk of disease. Contemporary human populations are no longer faced with the challenges of our ancestors such as …

Synaptic And Circuit Mechanisms Of Glutamate Spillover Signaling, Luke Teichert Coddington

All ETDs from UAB

Glutamate is the most prominent fast excitatory neurotransmitter released at mammalian central synapses, where point-to-point activation of receptors in postsynaptic densities is accepted to be the primary pathway for information flow through neural circuits. More controversial are the activities of synaptically-released glutamate outside the synaptic cleft of origin, as "spillover" glutamate may signal through neighboring synapses or through extrasynaptic receptors. The role of such extrasynaptic signaling in physiological neuronal communication is unproven and its inappropriate occurrence has been proposed to underlie a range of neurodegenerative conditions. Elucidation of spillover signaling mechanisms thus benefits our understanding of the brain in both …

Conformational Changes And Translocation Of Tissue-Transglutaminase To The Plasma Membranes: Role In Cancer Cell Migration, Ambrish Kumar, Jianjun Hu, Holly A. Lavoie, Kenneth B. Walsh, Donald J. Dipette, Ugra S. Singh

Faculty Publications

Background

Tissue-transglutaminase (TG2), a dual function G-protein, plays key roles in cell differentiation and migration. In our previous studies we reported the mechanism of TG2-induced cell differentiation. In present study, we explored the mechanism of how TG2 may be involved in cell migration.

Methods

To study the mechanism of TG2-mediated cell migration, we used neuroblastoma cells (SH-SY5Y) which do not express TG2, neuroblastoma cells expressing exogenous TG2 (SHY_TG2), and pancreatic cancer cells which express high levels of endogenous TG2. Resveratrol, a natural compound previously shown to inhibit neuroblastoma and pancreatic cancer in the animal models, was utilized to …

Empirical Models Of Scalp-Eeg Responses Using Non-Concurrent Intracranial Responses, Komalpreet Kaur, Jerry J. Shih, Dean J. Krusienski

Electrical & Computer Engineering Faculty Publications

Objective- This study presents inter-subject models of scalp-recorded electroencephalographic (sEEG) event-related potentials (ERPs) using intracranially recorded ERPs from electrocorticography and stereotactic depth electrodes in the hippocampus, generally termed as intracranial EEG (iEEG).

Approach- The participants were six patients with medically-intractable epilepsy that underwent temporary placement of intracranial electrode arrays to localize seizure foci. Participants performed one experimental session using a brain-computer interface matrix spelling paradigm controlled by sEEG prior to the iEEG electrode implantation, and one or more identical sessions controlled by iEEG after implantation. All participants were able to achieve excellent spelling accuracy using sEEG, four of the participants …

Hypothesis Testing In Normal Admixture Models To Detect Heterogeneous Genetic Signals, Qian Fan, Richard Charnigo, Zohreh Talebizadeh, Hongying Dai

Manuscripts, Articles, Book Chapters and Other Papers

In this work we consider a three-component normal mixture model in which one component is known to have mean zero and the other two contaminating components have a nonnegative and a nonpositive mean respectively, while all three components share a common unknown variance parameter. One potential application of this model may be in prioritizing statistical scores obtained in biological experiments, including genetics data. Such a mixture model may be useful in describing the distribution of numerous Z test statistics corresponding to different genes or SNPs, such that a “significant” Z test statistic for a particular gene suggests its connection to …

American And Brazilian Children With Primary Urolithiasis: Similarities And Disparities., Maria Goretti Moreira Guimarães Penido, Marcelo De Sousa Tavares, Milena Maria Moreira Guimarães, Tarak Srivastava, Uri S. Alon

Manuscripts, Articles, Book Chapters and Other Papers

Objectives. Considering the differences in location, socioeconomic background, and cultural background, the aim of this study was to try to identify possible factors associated with the increased incidence of urolithiasis by comparing American and Brazilian children with stones.
Methods. Data of 222 American and 190 Brazilian children with urolithiasis were reviewed including age, gender, body mass index, imaging technique used (ultrasound and computed tomography), and 24-hour urine volume and chemistries.
Results. There were no differences between age and gender at diagnosis. Brazilian children were leaner but in no population did obesity rate exceed that of the general population. Ultrasound was …

Transmural Heterogeneity Of Cellular Level Cardiac Contractile Properties In Aging And Heart Failure, Premi Haynes

Theses and Dissertations--Physiology

The left ventricle of the heart relaxes when it fills with blood and contracts to eject blood into circulation to meet the body’s metabolic demands. Dysfunction in either relaxation or contraction of the left ventricle can lead to heart failure. Transmural heterogeneity is thought to contribute to normal ventricular wall motion but it is not well understood how transmural modifications affect the failing left ventricle. The overall hypothesis of this dissertation is that normal left ventricles exhibit transmural heterogeneity in cellular level contractile properties and with aging and heart failure there are region-specific changes in cellular level contractile mechanisms.

Age …

Comparison Of The Effect Of Two Human Milk Fortifiers On Clinical Outcomes In Premature Infants, Melissa Thoene, Corrine K. Hanson, Elizabeth Lyden, Laura Dugick, Leslie Ruybal, Ann Anderson-Berry

Journal Articles: Nebraska Medicine

The use of human milk fortifiers (HMF) helps to meet the high nutritional requirements of the human milk-fed premature infant. Previously available powdered products have not met the protein requirements of the preterm infant population and many neonatologists add powder protein modulars to help meet protein needs. The use of powdered products is discouraged in neonatal intensive care units (NICU) due to concern for invasive infection. The use of a commercially available acidified liquid product with higher protein content was implemented to address these two concerns. During the course of this implementation, poor growth and clinically significant acidosis of infants …

Vitamin C As An Antioxidant: Evaluation Of Its Role On Pulmonary Contusion Experimental Model, Rana Sirmali, Zeynep Gi̇ni̇ş, Mehmet Sirmali, Okan Solak, Bengü Şeli̇man, Yetki̇n Ağaçkiran, Namik Deli̇baş

Turkish Journal of Medical Sciences

To analyze the protective activity of vitamin C on the lungs by assessing biochemical and histopathological analysis after performing an experimental isolated lung contusion model. Materials and methods: Fifty-four male Sprague-Dawley male rats were used. The rats were randomly separated into 4 groups. Vitamin C (200 mg/kg) was injected intraperitoneally 30 min after trauma. Blood samples were obtained for myeloperoxidase (MPO), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities and malondialdehyde (MDA) levels. Blood gas analysis and bronchoalveolar lavage was performed. The lung tissue was also extracted for histopathological examination. Results: The lung contusion enhanced MDA, SOD, CAT, …

Evaluation Of 4 Methods For The Serological Diagnosis Of Epstein–Barr Virus Infection Using An Immunofluorescence Assay As The Reference Method, Mücahi̇de Esra Koçoğlu, Teki̇n Taş, Firat Zafer Mengeloğlu, Şeyda Özsoy, Özlem Bucak

Turkish Journal of Medical Sciences

Tests specific for VCA IgM, VCA IgG, and EBNA IgG are used to diagnose Epstein-Barr virus (EBV) infections and interpret disease status. The immunofluorescence assay (IFA) is accepted as the “gold standard” test. The purpose of this study was to evaluate the performance of 4 methods in comparison with IFA. Materials and methods: In total, 101 serum samples were obtained from clinically suspected cases of EBV infection between May 2010 and May 2012 and evaluated by IFA. All serum samples were analyzed by an immunoblot assay, enzyme-linked fluorescent assay (ELFA), enzyme immunoassay (EIA), and immunochromatographic assay (ICA). Results: ELFA and …

Cell Apoptosis And Proliferation In Rat Brains After Intracerebral Hemorrhage: Role Of Wnt/\Beta-Catenin Signaling Pathway, Ling Zhou, Li Deng, Neng Bin Chang, Ling Dou, Chao Xian Yang

Turkish Journal of Medical Sciences

To investigate the role of Wnt/\beta-catenin signaling pathway in cell apoptosis and proliferation in intracerebral hemorrhage (ICH) in rats. Materials and methods: The ICH rats were established by stereotaxic infusion of 50 µL autologous arterial blood into the right striatum. Pathological characteristics of brain tissue was assessed by hematoxylin and eosin and TUNEL staining, and the expressions of proliferating cell nuclear antigen (PCNA) and Wnt3a/\beta-catenin/cyclin D1 were investigated by immunohistochemistry or reverse-transcription polymerase chain reaction. Results: The number of apoptotic cells and PCNA-positive cells kept increasing from the day following the ICH induction and reached a peak on the 3rd …

Investigation Of Serum Macrophage Migration Inhibitor Factor And Monocyte Chemotactic Protein-1 Levels In Irritable Bowel Syndrome, Feti̇ Tülübaş, Mustafa Oran, Rafet Mete, Fi̇li̇z Turan, Ahsen Yilmaz, Zeynep Deni̇z Yildiz, Ahmet Gürel

Turkish Journal of Medical Sciences

Irritable bowel syndrome (IBS), a functional disorder of the bowel, has been thought to result from immune activation. The aim of this study was to evaluate macrophage migration inhibitory factor (MMIF) and monocyte chemotactic protein-1 (MCP-1) levels in IBS patients. Materials and methods: We enrolled 30 IBS patients and 30 healthy controls. The MMIF and MCP-1 levels of all patients and controls were detected using commercial enzyme-linked immunosorbent assay kits. Results: Serum MMIF and MCP-1 levels were markedly higher in IBS patients than in controls. White blood cell, neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts did not differ significantly between …