Systems and Integrative Physiology Commons^™

Prolonged Qt Interval In Hiv-1 Infected Humanized Mice Treated Chronically With Dolutegravir/Tenofovir Disoproxil Fumarate/Emtricitabine, Ali Namvaran, Julian V. Garcia, Mahendran Ramasamy, Kayla Nguyen, Farzaneh Tavakkoli Ghazani, Bryan T. Hackfort, Prasanta Dash, Reagan E. Fisher, Benson J. Edagwa, Santhi Gorantla, Keshoer R. Bidasee

Journal Articles: Cellular & Integrative Physiology

The REPRIEVE Trial recently reported high rates of sudden cardiac death (SCD) middle-aged people living with HIV-1 infection (PWH) using the WHO/NIH-recommended two nucleoside reverse transcriptase inhibitors (NRTIs)/one integrase strand inhibitor (INSTI) regimen to manage HIV-1 viremia. To date, clinically relevant animal models to delineate underlying causes for this remain limited. Here, we assessed if HIV-1-infected NOD.Cg-Prkdc^scidIl2rg^tm1Wjl/SzJ humanized mice (Hu-mice) treated with the WHO/NIH-recommended antiretroviral regimen, dolutegravir (DTG, INSTI)/tenofovir disoproxil fumarate (TDF, NRTIs)/emtricitabine (FTC, NRTIs), can recapitulate abnormalities in the ECG and subclinical structural heart disease that serve as harbingers of SCD in middle-aged PWH. …

Attenuation Of Cardiac Dysfunction In The Collagen-Induced Arthritis Mouse Model Mediated By A Reactive Aldehyde Species Inhibitor, Wenxian Zhou, Hannah J. Johnson, Michael J. Duryee, Ali Namvaran, Aradhana Thapa, Cole Blasing, Amy J. Nelson, Engle E. Sharp, Carlos D. Hunter, Bryan T. Hackfort, Bryant England, Tate M. Johnson, Daniel R. Anderson, Adam Lazorchak, Robert G. Bennett, Jill A. Poole, Keshoer R. Bidasee, Geoffrey M. Thiele, Ted R. Mikuls

Journal Articles: Cellular & Integrative Physiology

Individuals with rheumatoid arthritis (RA) experience increased risk of heart failure. Malondialdehyde-acetaldehyde (MAA) adducts are overexpressed and co-localize with citrullinated (CIT) proteins in RA myocardium. This study investigated whether reactive aldehyde species (RASP) inhibitors prevent MAA formation in vitro and attenuate cardiac dysfunction in a collagen-induced arthritis (CIA) mouse model. Among eight RASP inhibitors screened, ADX-246 demonstrated the greatest inhibition of MAA formation in vitro. Mice with early CIA (week 5) exhibited elevated levels of myocardial MAA adducts, myocardial inflammation, and reduced ejection fraction, but normal cardiac collagen deposition and diastolic function vs. control. By weeks 10-12, mice with chronic …

Associations And Condition Sensitivity Of Smartphone-And Force-Plate-Derived Sway Metrics During Vr-Ctsib, Saeed Eshghi, Amin Mohammadi, Eric Schussler, Ryan S. Mccann

Rehabilitation Sciences Faculty Publications

Smartphone-based sensors may provide a complement to laboratory-based force-plate balance assessment; however, validation studies have not established whether smartphone–force-plate associations and agreement vary across combined manipulations of visual input and support-surface reliability, or which smartphone-derived metrics are most sensitive to sensory challenges. Therefore, this study compared smartphone-derived and force-plate-derived sway metrics during virtual reality-based clinical test of sensory interaction and balance (VR-CTSIB) conditions. This secondary analysis included 40 adults (20 with chronic ankle instability and 20 healthy controls). Participants completed 30 s double-leg stance trials under six VR-CTSIB conditions combining firm or foam surfaces with NormVision, DisplayOff, and SwayRef visual …

Over-Expression Of Copper/Zinc Superoxide Dismutase In The Median Preoptic Nucleus Attenuates Chronic Angiotensin Ii-Induced Hypertension In The Rat., John P. Collister, Mitch Bellrichard, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·-) scavenging enzyme, in …

Aberrant Promoter Cpg Methylation Is A Mechanism For Impaired Phd3 Expression In A Diverse Set Of Malignant Cells., Trenton L. Place, Matthew P. Fitzgerald, Sujatha Venkataraman, Sabine U. Vorrink, Adam J. Case, Melissa L.T. Teoh, Frederick E. Domann

Journal Articles: Cellular & Integrative Physiology

BACKGROUND: The prolyl-hydroxylase domain family of enzymes (PHD1-3) plays an important role in the cellular response to hypoxia by negatively regulating HIF-α proteins. Disruption of this process can lead to up-regulation of factors that promote tumorigenesis. We observed decreased basal expression of PHD3 in prostate cancer tissue and tumor cell lines representing diverse tissues of origin. Furthermore, some cancer lines displayed a failure of PHD3 mRNA induction when introduced to a hypoxic environment. This study explores the mechanism by which malignancies neither basally express PHD3 nor induce PHD3 under hypoxic conditions.

METHODOLOGY/PRINCIPAL FINDINGS: Using bisulfite sequencing and methylated DNA enrichment …