Medicine and Health Sciences Commons^™

Reduction In Hepatic Inflammation Is Associated With Less Fibrosis Progression And Fewer Clinical Outcomes In Advanced Hepatitis C, Chihiro Morishima, Mitchell Shiffman, Jules Dienstag, Karen Lindsay, Gyongyi Szabo, Gregory Everson, Anna Lok, Adrian Di Bisceglie, Marc Ghany, Deepa Naishadham, Timothy Morgan, Elizabeth Wright

Gyongyi Szabo

OBJECTIVES:During the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial, 3.5 years of maintenance peginterferon-alfa-2a therapy did not affect liver fibrosis progression or clinical outcomes among 1,050 previous interferon nonresponders with advanced fibrosis or cirrhosis. We investigated whether reduced hepatic inflammation was associated with clinical benefit in 834 patients with a baseline and follow-up biopsy 1.5 years after randomization to peginterferon or observation. METHODS:Relationships between change in hepatic inflammation (Ishak hepatic activity index, (HAI)) and serum alanine aminotransferase level, fibrosis progression and clinical outcomes after randomization, and hepatitis C virus (HCV) RNA decline before and after randomization were evaluated. Histological …

Neurosteroid-Mediated Regulation Of Brain Innate Immunity In Hiv/Aids: Dhea-S Suppresses Neurovirulence, Amber Paul, Ferdinand G. Maingat, Maria J. Polyak, Pornpun Vivithanaporn, Farshid Noorbakhsh, Samir Ahboucha, Glen B. Baker, Keir Pearson, Christopher Power

Publications

Neurosteroids are cholesterol-derived molecules synthesized within the brain, which exert trophic and protective actions. Infection by human and feline immunodeficiency viruses (HIV and FIV, respectively) causes neuroinflammation and neurodegeneration, leading to neurological deficits. Secretion of neuroinflammatory host and viral factors by glia and infiltrating leukocytes mediates the principal neuropathogenic mechanisms during, although the effect of neurosteroids on these processes is unknown. We investigated the interactions between neurosteroid mediated effects and lentivirus infection outcomes. Analyses of HIV-infected uninfected human brains disclosed a reduction in neurosteroid synthesis enzyme expression. Human neurons exposed to supernatants from HIV macrophages exhibited suppressed enzyme expression without …

Residential Traffic Exposure, Pulse Pressure, And C-Reactive Protein: Consistency And Contrast Among Exposure Characterization Methods, Christine L. Rioux, Katherine L. Tucker, Mkaya Mwamburi, David M. Gute, Steven A. Cohen, Doug Brugge

Katherine L. Tucker

Background: Traffic exposure may increase cardiovascular disease (CVD) risk via systemic inflammation and elevated blood pressure, two important clinical markers for managing disease progression. Objectives: We assessed degree and consistency of association between traffic exposure indicators as predictors of C-reactive protein (CRP) and pulse pressure (PP) in an adult U.S. Puerto Rican population (n = 1,017). Methods: Cross-sectional information on health and demographics and blood data was collected. Using multiple linear regression, we tested for associations between CRP, PP, and six traffic exposure indicators including residential proximity to roads with > 20,000 vehicles/day and traffic density [vehicle miles traveled per square …

Novel Use Of Dual Anti-Inflammatory Therapy To Overcome Drug Resistance And Improve Functional Recovery Following Spinal Cord Injury, Jennifer Dulin

Dissertations & Theses (Open Access)

Over 1.2 million Americans are currently living with a traumatic spinal cord injury (SCI). Despite the need for effective therapies, there are currently no proven effective treatments that can improve recovery of function in SCI patients. Many therapeutic compounds have shown promise in preclinical models of SCI, but all of these have fallen short in clinical trials.

P-glycoprotein (Pgp) is an active transporter expressed on capillary endothelial cell membranes at the blood-spinal cord barrier (BSCB). Pgp limits passive diffusion of blood-borne drugs into the CNS, by actively extruding drugs from the endothelial cell membrane. Pgp can become pathologically up-regulated, thus …