Medical Physiology Commons^™

Seeing The Invisible: Revealing Atrial Ablation Lesions Using Hyperspectral Imaging Approach, Narine Muselimyan, Luther Swift, Huda Asfour, Tigran Chahbazian, Ramesh Mazhari, Marco Mercader, Narine Sarvazyan

Pharmacology and Physiology Faculty Publications

Background

Currently, there are limited means for high-resolution monitoring of tissue injury during radiofrequency ablation procedures.

Objective

To develop the next generation of visualization catheters that can reveal irreversible atrial muscle damage caused by ablation and identify viability gaps between the lesions.

Methods

Radiofrequency lesions were placed on the endocardial surfaces of excised human and bovine atria and left ventricles of blood perfused rat hearts. Tissue was illuminated with 365nm light and a series of images were acquired from individual spectral bands within 420-720nm range. By extracting spectral profiles of individual pixels and spectral unmixing, the relative contribution of ablated …

The Role Of The Mir-200 Family On The Tumor Suppressor Rassf2 And The Effect On Mapk Pathway Activity In Colorectal Cancer., Jane V. Carter

Electronic Theses and Dissertations

This dissertation investigated the role of the miR-200 family in normal colon epithelial (CCD 841) and Dukes’ C (HT-29) colorectal cancer (CRC) cell lines. Our aim was to characterize expression of the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141, and miR-429) in colorectal cell lines, study their effect on the tumor suppressor Ras Associated Domain-Containing Protein (RASSF) 2 and on subsequent activity within the mitogen-activated protein kinase (MAPK) signaling pathway. We wanted to determine whether regulation of miR-200 family members could change cell behavior towards more “cancer-like” in a normal colon epithelium (CCD 841) cell line, or less “cancer-like” in a …

Evaluating Cardiovascular Dysfunction During Increased Activity And Exercise Rehabilitation Following Incomplete Thoracic Spinal Cord Injury In The Adult Rat., Kathryn A. Harman

Electronic Theses and Dissertations

Spinal cord injury (SCI) results in whole-body dysfunction. While the majority of SCI research is focused on improving locomotor function after injury, cardiovascular (CV) disease continues to be the leading cause of morbidity in the chronic SCI patient population. The combination of injury-induced destruction of autonomic pathways, maladaptive plasticity within lumbosacral circuits, and the progressive decline in physical fitness contribute to the poor CV status of SCI individuals. Currently, there is little emphasis on implementing appropriately-timed acute rehabilitation techniques aimed to curtail maladaptive remodeling and improve CV outcomes. Furthermore, no pre-clinical or clinical studies have investigated the most appropriate time-course …

Neuroprotective Molecules And Strategies In A Rat Model Of Neonatal Hypoxic Ischemic Encephalopathy, Brandon Joseph Dixon

Loma Linda University Electronic Theses, Dissertations & Projects

Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating disease that primarily causes neuronal and white matter injury and is among the leading cause of death among infants. Currently there are no well-established treatments; thus, it is important to understand the pathophysiology of the disease and elucidate complications that are creating a gap between basic science and clinical translation. In the development of neuroprotective strategies and translation of experimental results in HIE, there are many limitations and challenges to master based on an appropriate study design, drug delivery properties, dosage, and use in neonates. Since there are no established therapies for …

Role Of Occludin In The Regulation Of Epithelial Tight Junctions, Bhargavi Manda

Theses and Dissertations (ETD)

Tight junctions (TJ) constitute the primary component of epithelial barrier function, a disruption of which is involved in the pathogenesis of many gastrointestinal, pulmonary and renal diseases. Occludin is the major transmembrane protein of TJ, a deletion of which leads to a complex phenotype including chronic inflammation in several epithelial tissues of occludin deficient mice and poor TJ integrity in epithelial cell lines. Its down regulation was seen in Crohn’s disease, tumors of the colon, brain, endometrium and breast cancer. Occludin is also known to be a target that enables Hepatitis C Virus infection and bacterial pathogenesis. But the specific …

Dissecting The Physiological Roles Of Ulk1/2 In The Mouse Brain, Bo Wang

Theses and Dissertations (ETD)

Mammalian UNC-51–like kinases 1 and 2 (ULK1 and ULK2), Caenorhabditis elegans UNC-51 and Drosophila melanogaster Atg1 are redundant serine/threonine kinases that regulate flux through the autophagy pathway in response to various types of cellular stress. C. elegans UNC-51 and D. melanogaster Atg1 also promote axonal growth and defasciculation, and disruption of these genes results in defects in axon guidance in invertebrates. Germline Ulk1/2-deficient mice die perinatally. Therefore, we used a conditional-knockout approach to investigate the roles of ULK1/2 in the brain. Mice lacking Ulk1 and Ulk2 in their central nervous systems (CNS) showed defects in axonal pathfinding and defasciculation affecting …

Development Of Activity In The Mouse Visual Cortex., Jing Shen, Matthew T Colonnese

Pharmacology and Physiology Faculty Publications

No abstract provided.

Increased Mitochondrial Superoxide In The Brain, But Not Periphery, Sensitizes Mice To Angiotensin Ii-Mediated Hypertension., Adam J. Case, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Angiotensin II (AngII) elicits the production of superoxide (O2(•-)) from mitochondria in numerous cell types within peripheral organs and in the brain suggesting a role for mitochondrial-produced O2(•-) in the pathogenesis of hypertension. However, it remains unclear if mitochondrial O2(•-) is causal in the development of AngII-induced hypertension, or if mitochondrial O2(•-) in the absence of elevated AngII is sufficient to increase blood pressure. Further, the tissue specific (i.e. central versus peripheral) redox regulation of AngII hypertension remains elusive. Herein, we hypothesized that increased mitochondrial O2(•-) in the absence of pro-hypertensive stimuli, such as AngII, elevates baseline systemic mean arterial …

Intranasal Oxytocin Enhances Connectivity In The Neural Circuitry Supporting Social Motivation And Social Perception In Children With Autism., Ilanit Gordon, Allison Jack, Charlotte M Pretzsch, Brent Vander Wyk, James F Leckman, Ruth Feldman, Kevin A. Pelphrey

Pharmacology and Physiology Faculty Publications

Oxytocin (OT) has become a focus in investigations of autism spectrum disorder (ASD). The social deficits that characterize ASD may relate to reduced connectivity between brain sites on the mesolimbic reward pathway (nucleus accumbens; amygdala) that receive OT projections and contribute to social motivation, and cortical sites involved in social perception. Using functional magnetic resonance imaging and a randomized, double blind, placebo-controlled crossover design, we show that OT administration in ASD increases activity in brain regions important for perceiving social-emotional information. Further, OT enhances connectivity between nodes of the brain's reward and socioemotional processing systems, and does so preferentially for …

Positive Allosteric Modulator Of Gabab Receptor Alters Behavioral Effects But Not Afterdischarge Progression Induced By Partial Hippocampal Kindling., L Stan Leung, Miao Jin, Liangwei Chu, Jingyi Ma

Physiology and Pharmacology Publications

Hippocampal seizures decreased the function of GABAB receptors, which may further increase seizure susceptibility and contribute to development of schizophrenia-like behaviors. Recent literature indicates that GABAB receptor agonist may normalize schizophrenia-like behaviors and prevent drug-induced behavioral sensitization. We hypothesized that positive modulation of GABAB receptor function during seizure induction will reduce seizure-induced schizophrenia-like behaviors. Using a partial hippocampal kindling model, afterdischarges were induced after injection of saline or dimethyl sulfoxide (vehicle-kindled rats), or a GABAB receptor positive allosteric modulator CGP7930, at 1 mg/kg i.p. (CGP1-kindled) or 5 mg/kg i.p. (CGP5-kindled). The increase in the primary afterdischarge duration during kindling was …

Mitochondrial Superoxide Signaling Contributes To Norepinephrine-Mediated T-Lymphocyte Cytokine Profiles., Adam J. Case, Colton T. Roessner, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Norepinephrine (NE) produces multifaceted regulatory patterns in T-lymphocytes. Recently, we have shown that NE utilizes redox signaling as evidenced by increased superoxide (O2●-) causally linked to the observed changes in these cells; however, the source of this reactive oxygen species (ROS) remains elusive. Herein, we hypothesized that the source of increased O2●- in NE-stimulated T-lymphocytes is due to disruption of mitochondrial bioenergetics. To address this hypothesis, we utilized purified mouse splenic CD4+ and CD8+ T-lymphocytes stimulated with NE and assessed O2●- levels, mitochondrial metabolism, cellular proliferation, and cytokine profiles. We demonstrate that the increase in O2●- levels in response to …

The Beta-1-Receptor Blocker Nebivolol Elicits Dilation Of Cerebral Arteries By Reducing Smooth Muscle [Ca2+]I, Peter Cseplo, Zoltan Vamos, Ivan Ivic, Orsolya Torok, Attila Toth, Akos Koller

NYMC Faculty Publications

RATIONALE: Nebivolol is known to have beta-1 blocker activity, but it was also suggested that it elicits relaxation of the peripheral arteries in part via release of nitric oxide (NO). However, the effect of nebivolol on the vasomotor tone of cerebral arteries is still unclear.

OBJECTIVE: To assess the effects of nebivolol on the diameter of isolated rat basilar arteries (BA) in control, in the presence of inhibitors of vasomotor signaling pathways of know action and hemolysed blood.

METHODS AND RESULTS: Vasomotor responses were measured by videomicroscopy and the intracellular Ca2+ by the Fura-2 AM ratiometric method. Under control conditions, …

An Excitatory Cortical Feedback Loop Gates Retinal Wave Transmission In Rodent Thalamus, Yasunobu Murata, Matthew T. Colonnese

Pharmacology and Physiology Faculty Publications

Spontaneous retinal waves are critical for the development of receptive fields in visual thalamus (LGN) and cortex (VC). Despite a detailed understanding of the circuit specializations in retina that generate waves, whether central circuit specializations also exist to control their propagation through visual pathways of the brain is unknown. Here we identify a developmentally transient, corticothalamic amplification of retinal drive to thalamus as a mechanism for retinal wave transmission in the infant rat brain. During the period of retinal waves, corticothalamic connections excite LGN, rather than driving feedforward inhibition as observed in the adult. This creates an excitatory feedback loop …

Reduced Motor Neuron Excitability Is An Important Contributor To Weakness In A Rat Model Of Sepsis, Paul Nardelli, Jacob A. Vincent, Randall K. Powers, Timothy C. Cope, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

The mechanisms by which sepsis triggers intensive care unit acquired weakness (ICUAW) remain unclear. We previously identified difficulty with motor unit recruitment in patients as a novel contributor to ICUAW. To study the mechanism underlying poor recruitment of motor units we used the rat cecal ligation and puncture model of sepsis. We identified striking dysfunction of alpha motor neurons during repetitive firing. Firing was more erratic, and often intermittent. Our data raised the possibility that reduced excitability of motor neurons was a significant contributor to weakness induced by sepsis. In this study we quantified the contribution of reduced motor neuron …

The Role Of O-Glcnacase During Heart Failure., Sujith Dassanayaka

Electronic Theses and Dissertations

Global augmentation of protein O-GlcNAcylation occurs in response to a myriad of stressors and confers a survival advantage at the cellular level. This protective phenomenon has been demonstrated to mediate cardioprotection through various in vitro and in vivo studies during ischemia-reperfusion, myocardial infarction, and oxidative stress; however, relatively little is known of the regulation of protein O-GlcNAcylation. Protein O-GlcNAcylation is regulated by two antagonistic enzymes, namely, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Ablation of cardiomyocyte OGT, the enzyme that catalyzes the addition of O-GlcNAc to proteins, exacerbates cardiac dysfunction during infarct-induced heart failure (HF). However, little is known of the …

Toll-Like Receptor 4 Mutation Suppresses Hyperhomocysteinemia-Mediated Hypertension., Anastasia Familtseva

Electronic Theses and Dissertations

Background: Hyperhomocysteinemia (HHcy) has been observed to promote hypertension, but the mechanisms are unclear. Toll-like receptor 4 (TLR-4) is a cellular membrane protein that is ubiquitously expressed in all cell types of the vasculature. TLR-4 activation has been shown to promote inflammation that has been associated with pathogenesis of hypertension. In this study, we hypothesize that HHcy induces hypertension by TLR-4 activation that promotes inflammatory cytokine up-regulation (IL-1β, IL-6, TNF-α) and initiation of mitochondrial dysfunction leading to cell death and chronic vascular inflammation. Methods: To test this hypothesis, we used C57BL/6J mice (WT); Cystathionine-β-synthase deficient mice (CBS+/-) with genetic mild …

Ovarian Tumour Growth Is Characterized By Mevalonate Pathway Gene Signature In An Orthotopic, Syngeneic Model Of Epithelial Ovarian Cancer., James B Greenaway, Carl Virtanen, Kata Osz, Tamas Revay, Daniel Hardy, Trevor Shepherd, Gabriel Dimattia, Jim Petrik

Physiology and Pharmacology Publications

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer and often is not detected until late stages when cancer cells transcoelomically metastasize to the abdomen and typically become resistant to therapy resulting in very low survival rates. We utilize an orthotopic, syngeneic mouse model to study late stage disease and have discovered that the tumor cells within the abdominal ascites are irreversibly re-programmed, with an increased tumorigenicity and resistance to apoptosis. The goal of this study was to characterize the reprogramming that occurred in the aggressive ascites-derived cells (28-2 cells) compared to the original cell line used for tumor …

Malignant Hyperthermia, Aaron Roth

Nursing Student Class Projects (Formerly MSN)

Malignant hyperthermia is a rare disease trait and can take place in a variety of settings. If not treated in a timely manner, the consequences will be dire. It is recommended that nurses and other healthcare personnel be properly educated on MH crises. By detecting the signs and symptoms associated with the disease, providers can efficiently remedy the crisis and save patient lives (Seifert, 2014). Since the discovery of dantrolene in 1975 and the advancement of genetics regarding MH, death rates dropped from about 80% to about 5% (Schneiderbanger et al., 2014). Today there is a MH group called the …

Combining Real-Time Fmri Neurofeedback Training Of The Dlpfc With N-Back Practice Results In Neuroplastic Effects Confined To The Neurofeedback Target Region, Matthew Sherwood, Michael P. Weisend, Jessica H. Kane, Jason G. Parker

Neuroscience, Cell Biology & Physiology Faculty Publications

In traditional fMRI, individuals respond to exogenous stimuli and are naïve to the effects of the stimuli on their neural activity patterns. Changes arising in the fMRI signal are analyzed post-hoc to elucidate the spatial and temporal activation of brain regions associated with the tasks performed. The advent of real-time fMRI has enabled a new method to systematically alter brain activity across space and time using neurofeedback training (NFT), providing a new tool to study internally-driven processes such as neuroplasticity. In this work, we combined n-back practice with fMRI-NFT of the left dorsolateral prefrontal cortex (DLPFC) to better understand the …

Complex Regional Pain Syndrome, Maria A. Hendrix

Nursing Student Class Projects (Formerly MSN)

Complex regional pain syndrome (CRPS) is a chronic and often disabling condition that is seen in many patients seeking pain management. The condition leaves patients in excruciating pain that is disproportionate to the inciting injury. In addition, patients with this pain disorder experience abnormal sensations such as cold and heat allodynia, hyperalgesia, edema, abnormal sudomotor activity and trophic changes (D. Lee et al., 2015). CRPS disproportionally affects four times as many women as men (Alexander, Peterlin, Perreault, Grothusen, & Schwartzman, 2012). There are two types of CRPS: type 1, often referred to as reflex sympathetic dystrophy (RSD), is not evident …