Diseases Commons^™

Bioengineered Lysozyme Reduces Bacterial Burden And Inflammation In A Murine Model Of Mucoid Pseudomonas Aeruginosa Lung Infection, Charlotte C. Teneback, Thomas C. Scanlon, Matthew J. Wargo, Jenna L. Bement, Karl E. Griswold, Laurie W. Leclair

Dartmouth Scholarship

The spread of drug-resistant bacterial pathogens is a growing global concern and has prompted an effort to explore potential adjuvant and alternative therapies derived from nature's repertoire of bactericidal proteins and peptides. In humans, the airway surface liquid layer is a rich source of antibiotics, and lysozyme represents one of the most abundant and effective antimicrobial components of airway secretions. Human lysozyme is active against both Gram-positive and Gram-negative bacteria, ac

Selective Effects Of Intrinsic A2aar Activity On Cardiac And Coronary Injuries With Lps Challenge, Melissa Reichelt, Kevin Ashton, S Mustafa, B Tang, Catherine Ledent, Xing Tan, John Headrick, R Morrison

Kevin Ashton

We assessed the impact of A2A adenosine receptor (A2AAR) knockout (KO) on LPS-triggered cardiovascular injuries, inflammation, gene expression and mortality. LPS precipitated cardiac injury, with 7-fold elevations in serum cardiac troponin I (cTnI) and 25–35% reductions in ventricular contractility. Coronary dysfunction was evident as a 20% reduction in reactive hyperaemic flows. A2AAR KO augmented cTnI release 3-fold without modifying ventricular dysfunction. Coronary effects of LPS and A2AAR KO were identical, and LPS no longer modified hyperaemia in A2AAR KO hearts. Effects of A2AAR activity were largely independent of shifts in acute phase reactants (CRP, haptoglobin) and circulating cytokines. Thus, up …

Cardiovascular Adenosine Receptors: Expression, Actions And Interactions, John Headrick, Kevin Ashton, Roselyn Rose'meyer, Jason Peart

Kevin Ashton

Intra- and extracellular adenosine levels rise in response to physiological stimuli and with metabolic/energetic perturbations, inflammatory challenge and tissue injury. Extracellular adenosine engages members of the G-protein coupled adenosine receptor (AR) family to mediate generally beneficial acute and adaptive responses within all constituent cells of the heart. In this way the four AR sub-types—A1, A2A, A2B, and A3Rs—regulate myocardial contraction, heart rate and conduction, adrenergic control, coronary vascular tone, cardiac and vascular growth, inflammatory–vascular cell interactions, and cellular stress-resistance, injury and death. The AR sub-types exert both distinct and overlapping effects, and may interact in mediating these cardiovascular responses. The …

Regulation Of Lipid Homeostasis, Inflammatory Signalling And Atherosclerosis By The Peroxisome Proliferator-Activated Receptor Delta, Lazar A. Bojic

Electronic Thesis and Dissertation Repository

The peroxisome proliferator-activated receptor (PPAR) δ is a ligand-dependent transcription factor that has been implicated in metabolic and inflammatory regulation. The molecular and physiological mechanisms by which PPARδ activation regulates lipid metabolism, inflammatory signaling and protection from atherosclerosis in states of metabolic disturbance such as insulin resistance and dyslipidemia, were investigated in a series of in vitro and in vivo studies. In vitro experiments demonstrated that PPARδ activation inhibits atherogenic lipoprotein-induced lipid accumulation and the associated proinflammatory responses. The primary mechanisms for these effects were increased fatty acid β-oxidation, decreased lipoprotein lipase (LPL) activity, reduced MAPK signaling and improved insulin …

Stimulation Through Tlr4 Increases Fviii Inhibitor Formation In A Mouse Model Of Hemophilia A, Claire K. Holley

Dissertations & Theses (Open Access)

Hemophilia A is a clotting disorder caused by functional factor VIII (FVIII) deficiency. About 25% of patients treated with therapeutic recombinant FVIII develop antibodies (inhibitors) that render subsequent FVIII treatments ineffective. The immune mechanisms of inhibitor formation are not entirely understood, but circumstantial evidence indicates a role for increased inflammatory response, possibly via stimulation of Toll-like receptors (TLRs), at the time of FVIII immunization. I hypothesized that stimulation through TLR4 in conjunction with FVIII treatments would increase the formation of FVIII inhibitors. To test this hypothesis, FVIII K.O. mice were injected with recombinant human FVIII with or without concomitant doses …

The Effect Of Statins On Testosterone In Men And Women, A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Mary Schooling, Shiu Lun Au Yeung, Guy Freeman, Benjamin J. Cowling

Publications and Research

Background
Statins are extensively used for cardiovascular disease prevention. Statins reduce mortality rates morethan other lipid-modulating drugs, although evidence from randomized controlled trials also suggests that statinsunexpectedly increase the risk of diabetes and improve immune function. Physiologically, statins would beexpected to lower androgens because statins inhibit production of the substrate for the local synthesis of androgens and statins’ pleiotropic effects are somewhat similar to the physiological effects of lowering testosterone, so we hypothesized that statins lower testosterone.

Methods
A meta-analysis of placebo-controlled randomized trials of statins to test the a priori hypothesis that statins lower testosterone. We searched the PubMed, …

What Is The Effectiveness Of Roxithromycin In Management Of The Signs And Symptoms Of Rheumatoid Arthritis?, Adriana Distanislao

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not roxithromycin is effective in management of the signs and symptoms of rheumatoid arthritis.

STUDY DESIGN: Review of three primary studies in the English language published in 2006, 2009, and 2011.

DATA SOURCES: Randomized, controlled and double blind clinical trials testing the effectiveness roxithromycin in management of inflammation and signs and symptoms of rheumatoid arthritis were found using the PubMed and Ovid databases.

OUTCOMES MEASURED: Improvement in the signs and symptoms of tenderness/inflammation using the American College of Rheumatology-20 (ACR-20) scoring approach, improvement of quality of …

Serum 25-Hydroxyvitamin D Levels And C-Reactive Protein In Persons With Human Immunodeficiency Virus Infection, C. Anderson Johnson, Kalpana Poudel-Tandukar, Krishna C. Poudel, Masamine Jimba, Jun Kobayashi, Paula Palmer

CGU Faculty Publications and Research

Human immunodeficiency virus (HIV) infection has frequently been associated with vitamin D deficiency as well as chronic inflammatory response. We tested the hypothesis of an independent relationship between serum concentrations of 25-hydroxyvitamin D [25(OH)D] and high-sensitivity C-reactive protein (CRP) in a cohort of HIV-positive people. A cross-sectional survey was conducted among 316 HIV-positive people (181 men and 135 women) aged 16 to 60 years residing in the Kathmandu Valley, Nepal. Serum high-sensitivity CRP concentrations and serum 25(OH)D levels were measured by the latex agglutination nephelometry method and the competitive protein-binding assay, respectively. The relationship between serum CRP concentrations and 25(OH)D …