Medical Physiology Commons^™

Lipid Regulation As A Critical Factor In The Development Of Alzheimer's Disease, Michael A. Castello

Loma Linda University Electronic Theses, Dissertations & Projects

Alzheimer’s disease (AD) is the most common form of dementia in the United States, representing around eighty percent of all cases. For more than two decades, researchers have been led by the amyloid cascade hypothesis, which assumes that accumulation of the amyloid peptide Aβ, derived by proteolytic processing from the amyloid precursor protein (APP), is the key pathogenic trigger in AD. To date, therapies have largely focused on removing Aβ from the brain, an approach that has produced disappointing clinical outcomes. I present an alternative hypothesis in which Aβ production and aggregation is a symptom of a larger, systemic disease …

Identifying The Molecular Mechanisms Of Early Cachexia Using Whole Transcriptome Sequencing In Muscle And Fat Biopsies From Cancer Patients, Amal Hussain Al Hadad

Dissertations

Cancer cachexia is responsible for one third of cancer–related deaths and contributes to the death of many others. More than 80% of cancer patients are cachectic towards the end of life. Despite intensive research, the mechanisms of cancer cachexia are still poorly understood. It is our hypothesis that identification of early changes in gene expression in cachexia will lead to an improved understanding of the mechanism that trigger this important problem in cancer patients. Thus, to shed light on the mechanisms involved in the major cachexia target tissues, we investigated the entire transcriptome in muscle and fat to identify altered …

Differential Activation Of Microglia In An In Vitro Model Of Intracerebral Hemorrhage, Bhakti Patel

Renée Crown University Honors Thesis Projects - All

An in vitro model of intracerebral hemorrhage was established to examine the protective versus cytotoxic roles of microglia in the context of mild versus severe injury. Co-cultures of microglia, astrocytes, and granule neurons were prepared from the cerebellar cortex of neonatal rats, and grown in standard medium containing fetal bovine serum or, in some cases, a serum-free chemically defined medium. To mimic hemorrhagic stroke, co-cultures grown for 7-8 days in vitro were challenged with two different concentrations of the toxic blood product hemin, corresponding to a mild versus a severe brain bleed. Immunocyto-chemical, real-time RT-PCR, iron deposition, and cell survival …

Coaching And Concussions: Prevention, Education, And Perspective, Colby J. Felts

Honors Thesis

The large participation of players and coaches in football has made it one of the most popular sports in America. Concussions have specifically gained national attention in football due to frequent, high impact collisions. A concussion injury poses a unique threat in high school football because of the developing adolescent brain and high participation numbers. Additionally, lack of medical personnel to diagnose concussions at the high school level imposes a legal duty on the coaches. The thesis develops a recommended plan of action for directors of Iowa high school football to assist in preserving the future of the sport. A …

Oral Vs. Nasal Breathing During Submaximal Aerobic Exercise, Chase Ovila Platt Lacomb

UNLV Theses, Dissertations, Professional Papers, and Capstones

When comparing oral breathing versus nasal breathing more volume of air can be transported through the oral passageway, but nasal breathing can lead to slower respiration rates and cleaner inspired air. The purpose of this study is to find the most efficient mode of breathing during different intensities of submaximal aerobic exercise. There were 9 males and 10 females that completed this study. First test was a VO₂ Max test, 3.0 mph for 3 minutes, with increases in 1.0 mph every minute after that. Using a regression equation running speeds were determined for each individual’s submaximal intensities. The desire …

Mindfulness-Based Stress Reduction And Transcendental Meditation: Current State Of Research, Adam Holt

Journal of Patient-Centered Research and Reviews

This article summarizes the current state of meditation research, specifically focusing on mindfulness-based stress reduction and transcendental meditation. Despite significant methodological problems with the studies reported to date on the subject, there is consistent evidence that meditation can produce changes in the nervous system and physiology of the meditator, and can help with various psychological markers of well-being. Regarding improvement in specific clinical diseases, research is generally mixed and preliminary. Strong recommendations cannot be made based on current evidence, and further studies are needed. In general, there is a stronger body of evidence supporting mindfulness-based stress reduction than for transcendental …

Exercise Ameliorates High Fat Diet Induced Cardiac Dysfunction By Increasing Interleukin 10., Varun Kesherwani, Vishalakshi Chavali, Bryan T. Hackfort, Suresh C. Tyagi, Paras K. Mishra

Journal Articles: Cellular & Integrative Physiology

Increasing evidence suggests that a sedentary lifestyle and a high fat diet (HFD) leads to cardiomyopathy. Moderate exercise ameliorates cardiac dysfunction, however underlying molecular mechanisms are poorly understood. Increased inflammation due to induction of pro-inflammatory cytokine such as tumor necrosis factor-alpha (TNF-α) and attenuation of anti-inflammatory cytokine such as interleukin 10 (IL-10) contributes to cardiac dysfunction in obese and diabetics. We hypothesized that exercise training ameliorates HFD- induced cardiac dysfunction by mitigating obesity and inflammation through upregulation of IL-10 and downregulation of TNF-α. To test this hypothesis, 8 week old, female C57BL/6J mice were fed with HFD and exercised (swimming …

Induction Of Autophagy Markers Is Associated With Attenuation Of Mir-133a In Diabetic Heart Failure Patients Undergoing Mechanical Unloading., Shyam Sundar Nandi, Michael J. Duryee, Hamid R. Shahshahan, Geoffrey M. Thiele, Daniel R. Anderson, Paras K. Mishra

Journal Articles: Cellular & Integrative Physiology

Autophagy is ubiquitous in all forms of heart failure and cardioprotective miR-133a is attenuated in human heart failure. Previous reports from heart failure patients undergoing left ventricular assist device (LVAD) implantation demonstrated that autophagy is upregulated in the LV of the failing human heart. Studies in the murine model show that diabetes downregulates miR-133a. However, the role of miR-133a in the regulation of autophagy in diabetic hearts is unclear. We tested the hypothesis that diabetes exacerbates cardiac autophagy by inhibiting miR-133a in heart failure patients undergoing LVAD implantation. The miRNA assay was performed on the LV of 15 diabetic (D) …

A Systems Approach To Stress, Stressors And Resilience In Humans, Barry S. Oken, Irina Chamine, Wayne W. Wakeland

Complex Systems Faculty Publications and Presentations

The paper focuses on the biology of stress and resilience and their biomarkers in humans from the system science perspective. A stressor pushes the physiological system away from its baseline state towards a lower utility state. The physiological system may return towards the original state in one attractor basin but may be shifted to a state in another, lower utility attractor basin. While some physiological changes induced by stressors may benefit health, there is often a chronic wear and tear cost due to implementing changes to enable the return of the system to its baseline state and maintain itself in …

Maternal Nicotine Exposure Leads To Impaired Disulfide Bond Formation And Augmented Endoplasmic Reticulum Stress In The Rat Placenta, Michael Wong, Catherine J. Nicholson, Alison C. Holloway, Daniwl Hardy

Physiology and Pharmacology Publications

Maternal nicotine exposure has been associated with many adverse fetal and placental outcomes. Although underlying mechanisms remain elusive, recent studies have identified that augmented endoplasmic reticulum (ER) stress is linked to placental insufficiency. Moreover, ER function depends on proper disulfide bond formation-a partially oxygen-dependent process mediated by protein disulfide isomerase (PDI) and ER oxidoreductases. Given that nicotine compromised placental development in the rat, and placental insufficiency has been associated with poor disulfide bond formation and ER stress, we hypothesized that maternal nicotine exposure leads to both placental ER stress and impaired disulfide bond formation. To test this hypothesis, female Wistar …

Exposure To Phthalates Affects Calcium Handling And Intercellular Connectivity Of Human Stem Cell-Derived Cardiomyocytes, Nikki G. Posnack, Rabia Idrees, Hao Ding, Rafael Jaimes Iii, Gulnaz Stybayeva, Zaruhi Karabekian, Michael A. Laflamme, Narine Sarvazyan

Pharmacology and Physiology Faculty Publications

Background

The pervasive nature of plastics has raised concerns about the impact of continuous exposure to plastic additives on human health. Of particular concern is the use of phthalates in the production of flexible polyvinyl chloride (PVC) products. Di-2-ethylhexyl-phthalate (DEHP) is a commonly used phthalate ester plasticizer that imparts flexibility and elasticity to PVC products. Recent epidemiological studies have reported correlations between urinary phthalate concentrations and cardiovascular disease, including an increased risk of high blood pressure and coronary risk. Yet, there is little direct evidence linking phthalate exposure to adverse effects in human cells, including cardiomyocytes.

Methods and Results

The …

Guidelines For Pre-Clinical Assessment Of The Acetylcholine Receptor-Specific Passive Transfer Myasthenia Gravis Model - Recommendations For Methods And Experimental Designs., Linda L. Kusner, Mario Losen, Angela Vincent, Jon Lindstrom, Socrates Tzartos, Konstantinos Lazaridis, Pilar Martinez-Martinez

Pharmacology and Physiology Faculty Publications

Antibodies against the muscle acetylcholine receptor (AChR) are the most common cause of myasthenia gravis (MG). Passive transfer of AChR antibodies from MG patients into animals reproduces key features of human disease, including antigenic modulation of the AChR, complement-mediated damage of the neuromuscular junction, and muscle weakness. Similarly, AChR antibodies generated by active immunization in experimental autoimmune MG models can subsequently be passively transferred to other animals and induce weakness. The passive transfer model is useful to test therapeutic strategies aimed at the effector mechanism of the autoantibodies. Here we summarize published and unpublished experience using the AChR passive transfer …

Voltage-Gated Na+ Channel Activity Increases Colon Cancer Transcriptional Activity And Invasion Via Persistent Mapk Signaling, Carrie D. House, Bi-Dar Wang, Kristin Ceniccola, Russell Williams, May Simaan, Norman H. Lee, +7 Additional Authors

Pharmacology and Physiology Faculty Publications

Functional expression of voltage-gated Na⁺ channels (VGSCs) has been demonstrated in multiple cancer cell types where channel activity induces invasive activity. The signaling mechanisms by which VGSCs promote oncogenesis remain poorly understood. We explored the signal transduction process critical to VGSC-mediated invasion on the basis of reports linking channel activity to gene expression changes in excitable cells. Coincidentally, many genes transcriptionally regulated by the SCN5A isoform in colon cancer have an over-representation of cis-acting sites for transcription factors phosphorylated by ERK1/2 MAPK. We hypothesized that VGSC activity promotes MAPK activation to induce transcriptional changes in invasion-related genes. Using …

The Role Of Occupational Therapy In Primary Care, Priti Patel

Occupational Therapy Doctorate Capstone Projects

The Capstone Project is focused on communicating, influencing and educating other health care professionals regarding the role of occupational therapy in the future model of primary care delivery initiated by the adoption of the Affordable Care Act and the Triple Aim Initiative. Currently, primary care, the largest health care platform in United States, is not inclusive of occupational therapy services. Occupational therapists have the scope, knowledge and understanding to be part of the redesigned team model of primary care. Educating those currently working in primary care about adding occupational therapy services can have a significant impact on the profession of …

Risperidone And Its Deconstructed Analogs: Functional Effects On The 5ht2ar, Sneha Shah

Theses and Dissertations

G protein-coupled receptors (GPCRs) are seven-transmembrane domain receptors that sense extracellular signal and activate intracellular signaling pathways. The serotonin 5HT2A receptor (or 2AR) is one of the GPCRs coupled to Gq proteins, activating PLC and hydrolyzing PIP2. This hydrolysis causes a diffusion of bound PIP2 away from the channel binding site resulting in G protein-gated inwardly rectifying K⁺ channel (GIRK) inhibition and a downstream stimulation of Ca²⁺ release from endoplasmic reticulum stores. Previous experiments have demonstrated that the serotonin 5HTA receptor is a target of serotonergic psychedelic drugs, such as LSD, and partially mediates the action of many …

Appropriate Timing Of Fluoxetine And Statin Delivery Reduces The Risk Of Secondary Bleeding In Ischemic Stroke Rats, Maria Helen Harley Balch, Moner A. Ragas, Danny Wright, Kenny Reynolds, Bryce Kerr, Adrian M. Corbett

Neuroscience, Cell Biology & Physiology Faculty Publications

Background: Ongoing clinical trials are testing the effect of fluoxetine delivered post-stroke where a majority of patients are taking statins. This study determined the influence of the timing of administration of fluoxetine and statin on the final infarct volume and the risk of secondary bleeding in an animal model of ischemic stroke.

Methods and findings: Ischemic strokes were induced by endothelin-1 injection into two cortical sites of 10-12 month old female rats, targeting the forelimb motor cortex. Combined medications (5 mg/kg fluoxetine and 1 mg/kg simvastatin) were orally administered either beginning 6-12 hours or 20-26 hours after stroke induction and …

The Skeletal Muscle Molecular Clock Regulates The Timing Of Substrate Metabolism And The Circadian Expression Of Titin-Cap, Brian A. Hodge

Theses and Dissertations--Physiology

Skeletal muscle is a major contributor to whole-body metabolism as it serves as a depot for both glucose and amino acids, and is a highly metabolically active tissue. An intrinsic molecular clock mechanism exists within skeletal muscle that regulates the timing of physiological processes. A key function of the clock is to regulate the timing of metabolic processes to anticipate time of day changes in environmental conditions. The purpose of this study was to identify metabolic genes that are expressed in a circadian manner and determine if these genes are regulated downstream of the intrinsic molecular clock by assaying gene …

Inverse Relationship Between Physical Activity, Adiposity And Arterial Stiffness In Healthy Middle-Aged Subjects, Oscar Mac Ananey, B Mc Loughlin, A Leonard, L Maher, P Gaffney, G Boran, V Maher

Articles

BACKGROUND:

Several obesity related factors are reported to exacerbate premature arterial stiffening, including inactivity and metabolic disarray. The aim of the present study was to investigate the relationship between physical activity, arterial stiffness and adiposity using objective methods. To further explore the role of adiposity in this complex process, obesity associated anthropometric and humoral biomarkers were measured.

METHODS:

Seventy-nine healthy, lifelong non-smoking, subjects were recruited. Habitual physical activity was measured using accelerometry. Arterial stiffness (augmentation index; AIx & pulse wave velocity; PWV), was measured using tonometry. Body composition was estimated using bioimpedence. Adipose associated biomarkers, leptin and adiponectin, were also …

Inhibition Of Mtor Signaling Protects Against Myocardial Reperfusion Injury, Acute Myocardial Infarction, Scott M. Filippone

Theses and Dissertations

Acute myocardial infarction (AMI) is the leading cause of death worldwide. Currently, the best method of treating cardiac ischemia is early reperfusion which, itself, induces myocardial damage. The mTOR complex is a key regulator of cardioprotection against cell stressors. We hypothesized that reperfusion therapy with Rapamycin, a potent mTOR inhibitor, would reduce infarct size in adult mouse hearts. Rapamycin was administered at the onset of reperfusion following 30 min in situ LAD ligation. After 24 hours of reperfusion, myocardial infarct size and apoptosis were significantly reduced in rapamycin-treated mice compared to control. Rapamycin inhibited pro-apoptotic protein Bax and phosphorylation of …

Conduction States Of The Human Dopamine Transporter, Krasnodara Cameron

Theses and Dissertations

Dysregulation of dopaminergic homeostasis has been established as the primary source of numerous neurological disorders including Parkinson’s and drug addiction. A tonic increase of dopamine (DA) in the nucleus accumbens is required for associating everyday events and behaviors with rewards. Yet many addictive exogenous compounds such as amphetamine (AMPH) and cocaine (COC) produce a much greater augmentation of synaptic DA levels that are linked to euphoria and a shift in behavior towards drug seeking. The protein responsible for maintaining extracellular levels of DA is the dopamine transporter (DAT). It is primarily located in the perisynaptic area at terminals of pre-synaptic …