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Norman haughey

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https://www.readbyqxmd.com/read/29147885/proceedings-of-the-2017-isev-symposium-on-hiv-neurohiv-drug-abuse-evs
#1
Guoku Hu, Sowmya Yelamanchili, Fatah Kashanchi, Norman Haughey, Vincent C Bond, Kenneth W Witwer, Lynn Pulliam, Shilpa Buch
Despite the success of combination antiretroviral therapy (cART), there is increased prevalence of HIV-associated neurocognitive disorders (HAND) in HIV-1-infected individuals on cART, which poses a major health care challenge. Adding further complexity to this long-term antiretroviral use is the comorbidity with drugs of abuse such as morphine, cocaine, and methamphetamine, which can in turn, exacerbate neurologic and cognitive deficits associated with HAND. Furthermore, HIV proteins, such as the transactivator of transcription (Tat) and the envelope protein (gp120), as well as antiretrovirals themselves can also contribute to the progression of neurodegeneration underlying HAND...
November 16, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/29063516/paroxetine-and-fluconazole-therapy-for-hiv-associated-neurocognitive-impairment-results-from-a-double-blind-placebo-controlled-trial
#2
Ned Sacktor, Richard L Skolasky, Richard Moxley, Sheng Wang, Michelle M Mielke, Cynthia Munro, Joseph Steiner, Avindra Nath, Norman Haughey, Justin McArthur
Paroxetine and fluconazole have neuroprotective effects in an in vitro model of HIV protein-mediated neuronal injury. This study evaluated the safety, tolerability, and efficacy of both paroxetine and fluconazole for the treatment of HIV-associated neurocognitive disorder (HAND). A 24-week randomized double-blind, placebo-controlled 2 × 2 factorial design study was used. HIV+ individuals with cognitive impairment were enrolled in the 24-week trial. Participants were randomly assigned to one of four groups: (1) paroxetine 20 mg/day, (2) fluconazole 100 mg every 12 h, (3) paroxetine and fluconazole, or (4) placebo...
October 23, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/29020847/sphingolipids-and-microrna-changes-in-blood-following-blast-traumatic-brain-injury-an-exploratory-study
#3
Venkata Siva Sai Sujith Sajja, Anna Jablonska, Norman Haughey, Jeff W M Bulte, Robert D Stevens, Joseph B Long, Piotr Walczak, Miroslaw Janowski
At present, accurate and reliable biomarkers to ascertain the presence, severity, or prognosis of blast traumatic brain injury (bTBI) are lacking. There is an urgent need to establish accurate and reliable biomarkers capable of mbTBI detection. Currently, there are no studies that identify changes in miRNA and lipids at varied severities of bTBI. Various biological components such as lipids, circulating mRNA, and miRNA, could potentially be detected using advanced techniques such as next-generation sequencing and mass spectroscopy...
November 17, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28869672/internal-grant-review-to-increase-grant-funding-for-junior-investigators
#4
Heather S Thomas, Martin B Brodsky, Joshua B Ewen, Gregory K Bergey, Thomas E Lloyd, Norman J Haughey, Cherie L Marvel
No abstract text is available yet for this article.
October 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28851955/circulating-endothelial-cell-derived-extracellular-vesicles-mediate-the-acute-phase-response-and-sickness-behaviour-associated-with-cns-inflammation
#5
Yvonne Couch, Naveed Akbar, Jay Roodselaar, Matthew C Evans, Chris Gardiner, Ian Sargent, Ignacio A Romero, Adrian Bristow, Alastair M Buchan, Norman Haughey, Daniel C Anthony
Brain injury elicits a systemic acute-phase response (APR), which is responsible for co-ordinating the peripheral immunological response to injury. To date, the mechanisms responsible for signalling the presence of injury or disease to selectively activate responses in distant organs were unclear. Circulating endogenous extracellular vesicles (EVs) are increased after brain injury and have the potential to carry targeted injury signals around the body. Here, we examined the potential of EVs, isolated from rats after focal inflammatory brain lesions using IL-1β, to activate a systemic APR in recipient naïve rats, as well as the behavioural consequences of EV transfer...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28800366/proceedings-of-the-isev-symposium-on-hiv-neuroaids-drug-abuse-evs
#6
Guoku Hu, Kenneth W Witwer, Vincent C Bond, Norman Haughey, Fatah Kashanchi, Lynn Pulliam, Shilpa Buch
Extracellular vesicles (EVs) are globular, membrane bound nanovesicles (30-100 nm range) that are shed both during normal cellular functioning and under pathological conditions by most cell types. In recent years, there has been significant interest in the study of these vesicles as conduits for the delivery of information between cells from both analogous and disparate tissues. Their ability to carry specialised cargo including signalling mediators, proteins, messenger RNA and miRNAs characterises these vesicles as primary facilitators of cell-to-cell communication and regulation...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28798382/chronic-low-level-expression-of-hiv-1-tat-promotes-a-neurodegenerative-phenotype-with-aging
#7
Alex M Dickens, Seung Wan Yoo, Alfred C Chin, Jiadi Xu, Tory P Johnson, Amanda L Trout, Kurt F Hauser, Norman J Haughey
The widespread use of combinational antiretroviral therapies (cART) in developed countries has changed the course of Human Immunodeficiency Virus (HIV) infection from an almost universally fatal disease to a chronic infection for the majority of individuals. Although cART has reduced the severity of neurological damage in HIV-infected individuals, the likelihood of cognitive impairment increases with age, and duration of infection. As cART does not suppress the expression of HIV non-structural proteins, it has been proposed that a constitutive production of HIV regulatory proteins in infected brain cells may contribute to neurological damage...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28694327/efficacy-of-nutritional-interventions-to-lower-circulating-ceramides-in-young-adults-fruvedomic-pilot-study
#8
Alice T Mathews, Oluremi A Famodu, Melissa D Olfert, Pamela J Murray, Christopher F Cuff, Marianne T Downes, Norman J Haughey, Sarah E Colby, Paul D Chantler, I Mark Olfert, Joseph W McFadden
The 2010 USDA Dietary Guidelines for Americans (DGA) recommends a diet largely composed of fruit and vegetables. Consuming a diet high in fruit and vegetables and low in refined carbohydrates and saturated fat may reduce an individual's risk for type 2 diabetes, nonalcoholic fatty liver disease, low-grade chronic inflammation, and metabolic syndrome (MetS). Several recent studies have implicated the bioactive sphingolipid ceramide as an associative and causative biomarker for the development of these conditions...
July 2017: Physiological Reports
https://www.readbyqxmd.com/read/28598843/a-lipidomics-approach-to-assess-the%C3%A2-association-between-plasma-sphingolipids-and-verbal-memory-performance-in-coronary-artery-disease-patients-undertaking-cardiac-rehabilitation-a-c18-0-signature-for%C3%A2-cognitive-response-to-exercise
#9
Mahwesh Saleem, Nathan Herrmann, Adam Dinoff, Michelle M Mielke, Paul I Oh, Prathiba Shammi, Xingshan Cao, Swarajya Lakshmi Vattem Venkata, Norman J Haughey, Krista L Lanctôt
BACKGROUND: Early subtle deficits in verbal memory, which may indicate early neural risk, are common in patients with coronary artery disease (CAD). While exercise can improve cognition, cognitive response to exercise is heterogeneous. Sphingolipids have been associated with the development and progression of CAD, and impairments in sphingolipid metabolism may play roles in neurodegeneration and in the neural adaptation response to exercise. OBJECTIVE: In this study, change in plasma concentrations of sphingolipids was assessed in relation to change in verbal memory performance and in other cognitive domains among CAD subjects undertaking a 6-month cardiac rehabilitation (CR) program...
June 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28574961/modifications-in-acute-phase-and-complement-systems-predict-shifts-in-cognitive-status-of-hiv-infected-patients
#10
Ceereena Ubaida-Mohien, Benjamin Lamberty, Alex M Dickens, Michelle M Mielke, Thomas Marcotte, Ned Sacktor, Igor Grant, Scott Letendre, Donald Franklin, Pawel Cibrowski, Ravi Tharakan, Justin C McArthur, Howard Fox, Norman J Haughey
BACKGROUND: The prevalence of HIV-associated neurocognitive disorders (HAND) has not changed considerably in the last two decades. Potent antiretroviral therapy has shifted the severity of HAND to milder phenotypes, but excess morbidity and mortality continue to be associated with HAND. Changes in numerous markers of immune function, inflammation, and cellular stress have been repeatedly associated with HAND, but the underlying systems that drive these changes have not been identified...
June 19, 2017: AIDS
https://www.readbyqxmd.com/read/28537385/the-psychiatric-impact-of-hiv
#11
Michael T Nedelcovych, Arena A Manning, Svetlana Semenova, Charlene Gamaldo, Norman J Haughey, Barbara S Slusher
This Viewpoint is based on a recent panel featured at the 2017 Winter Conference on Brain Research in which the psychiatric comorbidities of HIV infection were discussed. Psychiatric comorbid conditions occur at high rates in HIV infected patients, complicating treatment and contributing to poor outcomes. A complex relationship between HIV infection and psychiatric comorbidity is an active area of investigation, but increased awareness of the impact of psychiatric complications of NeuroAIDS is needed in both the laboratory and the clinic to better understand and treat these interrelated conditions...
May 24, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28486481/temporal-changes-in-sphingolipids-and-systemic-insulin-sensitivity-during-the-transition-from-gestation-to-lactation
#12
J Eduardo Rico, Sina Saed Samii, Alice T Mathews, Jacqueline Lovett, Norman J Haughey, Joseph W McFadden
Reduced insulin action develops naturally during the peripartum to ensure maternal nutrient delivery to the fetus and neonate. However, increased insulin resistance can facilitate excessive lipolysis which in turn promotes metabolic disease in overweight dairy cattle. Increased fatty acid availability favors the accumulation of the sphingolipid ceramide and is implicated in the pathogenesis of insulin resistance, however, the relationship between sphingolipid metabolism and insulin resistance during the peripartum remains largely unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28398956/informatic-interrogation-of-csf-proteomic-profiles-from-hiv-infected-subjects-implicates-acute-phase-and-complement-systems-in-shifting-cognitive-status
#13
Ceereena Ubaida-Mohien, Benjamin Lamberty, Alex M Dickens, Michelle M Mielke, Thomas Marcotte, Ned Sacktor, Igor Grant, Scott Letendre, D Franklin, Pawel Cibrowski, Ravi Tharakan, Justin C McArthur, Howard Fox, Norman J Haughey
The prevalence of HIV-Associated Neurocognitive Disorders (HAND) has not changed considerably in the last two decades. Potent antiretroviral therapy (ART) has shifted the severity of HAND to milder phenotypes, but excess morbidity and mortality continue to be associated with HAND. Changes in numerous markers of immune function, inflammation and cellular stress have been repeatedly associated with HAND but the underlying systems that drive these changes have not been identified. In this study we used systems informatics to interrogate the CSF proteomic content of longitudinal samples obtained from HIV-infected adults with stably unimpaired, stably impaired, worsening, or improving neurocognitive (NC) performance...
April 10, 2017: AIDS
https://www.readbyqxmd.com/read/28377412/astrocyte-shed-extracellular-vesicles-regulate-the-peripheral-leukocyte-response-to-inflammatory-brain-lesions
#14
Alex M Dickens, Luis B Tovar-Y-Romo, Seung-Wan Yoo, Amanda L Trout, Mihyun Bae, Marlene Kanmogne, Bezawit Megra, Dionna W Williams, Kennith W Witwer, Mar Gacias, Nino Tabatadze, Robert N Cole, Patrizia Casaccia, Joan W Berman, Daniel C Anthony, Norman J Haughey
Brain injury induces a peripheral acute cytokine response that directs the transmigration of leukocytes into the brain. Because this brain-to-peripheral immune communication affects patient recovery, understanding its regulation is important. Using a mouse model of inflammatory brain injury, we set out to find a soluble mediator for this phenomenon. We found that extracellular vesicles (EVs) shed from astrocytes in response to intracerebral injection of interleukin-1β (IL-1β) rapidly entered into peripheral circulation and promoted the transmigration of leukocytes through modulation of the peripheral acute cytokine response...
April 4, 2017: Science Signaling
https://www.readbyqxmd.com/read/28218748/hiv-tat-protein-and-amyloid-%C3%AE-peptide-form-multifibrillar-structures-that-cause-neurotoxicity
#15
Alina Hategan, Mario A Bianchet, Joseph Steiner, Elena Karnaukhova, Eliezer Masliah, Adam Fields, Myoung-Hwa Lee, Alex M Dickens, Norman Haughey, Emilios K Dimitriadis, Avindra Nath
Deposition of amyloid-β plaques is increased in the brains of HIV-infected individuals, and the HIV transactivator of transcription (Tat) protein affects amyloidogenesis through several indirect mechanisms. Here, we investigated direct interactions between Tat and amyloid-β peptide. Our in vitro studies showed that in the presence of Tat, uniform amyloid fibrils become double twisted fibrils and further form populations of thick unstructured filaments and aggregates. Specifically, Tat binding to the exterior surfaces of the Aβ fibrils increases β-sheet formation and lateral aggregation into thick multifibrillar structures, thus producing fibers with increased rigidity and mechanical resistance...
April 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28035934/the-association-between-plasma-ceramides-and-sphingomyelins-and-risk-of-alzheimer-s-disease-differs-by-sex-and-apoe-in-the-baltimore-longitudinal-study-of-aging
#16
Michelle M Mielke, Norman J Haughey, Dingfen Han, Yang An, Veera Venkata Ratnam Bandaru, Constantine G Lyketsos, Luigi Ferrucci, Susan M Resnick
BACKGROUND: Cellular and animal studies demonstrated relationships between sphingolipid metabolism and Alzheimer's disease (AD) pathology. High blood ceramide levels have been shown to predict cognitive impairment and AD, but these studies had small sample sizes and did not assess differences in risk by sex or APOE genotype. OBJECTIVE: To determine whether plasma ceramides and sphingomyelins were associated with risk of AD, and whether the association varied by sex and APOE genotype...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27993242/hiv-protease-inhibitors-alter-amyloid-precursor-protein-processing-via-%C3%AE-site-amyloid-precursor-protein-cleaving-enzyme-1-translational-up-regulation
#17
Patrick J Gannon, Cagla Akay-Espinoza, Alan C Yee, Lisa A Briand, Michelle A Erickson, Benjamin B Gelman, Yan Gao, Norman J Haughey, M Christine Zink, Janice E Clements, Nicholas S Kim, Gabriel Van De Walle, Brigid K Jensen, Robert Vassar, R Christopher Pierce, Alexander J Gill, Dennis L Kolson, J Alan Diehl, Joseph L Mankowski, Kelly L Jordan-Sciutto
Mounting evidence implicates antiretroviral (ARV) drugs as potential contributors to the persistence and evolution of clinical and pathological presentation of HIV-associated neurocognitive disorders in the post-ARV era. Based on their ability to induce endoplasmic reticulum (ER) stress in various cell types, we hypothesized that ARV-mediated ER stress in the central nervous system resulted in chronic dysregulation of the unfolded protein response and altered amyloid precursor protein (APP) processing. We used in vitro and in vivo models to show that HIV protease inhibitor (PI) class ARVs induced neuronal damage and ER stress, leading to PKR-like ER kinase-dependent phosphorylation of the eukaryotic translation initiation factor 2α and enhanced translation of β-site APP cleaving enzyme-1 (BACE1)...
January 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/27379802/humoral-dysregulation-associated-with-increased-systemic-inflammation-among-injection-heroin-users
#18
Michael S Piepenbrink, Memorie Samuel, Bo Zheng, Brittany Carter, Christopher Fucile, Catherine Bunce, Michelle Kiebala, Atif A Khan, Juilee Thakar, Sanjay B Maggirwar, Diane Morse, Alexander F Rosenberg, Norman J Haughey, William Valenti, Michael C Keefer, James J Kobie
BACKGROUND: Injection drug use is a growing major public health concern. Injection drug users (IDUs) have a higher incidence of co-morbidities including HIV, Hepatitis, and other infections. An effective humoral response is critical for optimal homeostasis and protection from infection; however, the impact of injection heroin use on humoral immunity is poorly understood. We hypothesized that IDUs have altered B cell and antibody profiles. METHODS AND FINDINGS: A comprehensive systems biology-based cross-sectional assessment of 130 peripheral blood B cell flow cytometry- and plasma- based features was performed on HIV-/Hepatitis C-, active heroin IDUs who participated in a syringe exchange program (n = 19) and healthy control subjects (n = 19)...
2016: PloS One
https://www.readbyqxmd.com/read/27255825/peripheral-sphingolipids-are-associated-with-variation-in-white-matter-microstructure-in-older-adults
#19
Christopher E Gonzalez, Vijay K Venkatraman, Yang An, Bennett A Landman, Christos Davatzikos, Veera Venkata Ratnam Bandaru, Norman J Haughey, Luigi Ferrucci, Michelle M Mielke, Susan M Resnick
Sphingolipids serve important structural and functional roles in cellular membranes and myelin sheaths. Plasma sphingolipids have been shown to predict cognitive decline and Alzheimer's disease. However, the association between plasma sphingolipid levels and brain white matter (WM) microstructure has not been examined. We investigated whether plasma sphingolipids (ceramides and sphingomyelins) were associated with magnetic resonance imaging-based diffusion measures, fractional anisotropy (FA), and mean diffusivity, 10...
July 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/27135629/circulating-ceramides-are-inversely-associated-with-cardiorespiratory-fitness-in-participants-aged-54-96%C3%A2-years-from-the-baltimore-longitudinal-study-of-aging
#20
Elisa Fabbri, An Yang, Eleanor M Simonsick, Chee W Chia, Marco Zoli, Norman J Haughey, Michelle M Mielke, Luigi Ferrucci, Paul M Coen
Cardiorespiratory fitness (VO2 peak) declines with age and is an independent risk factor for morbidity and mortality in older adults. Identifying biomarkers of low fitness may provide insight for why some individuals experience an accelerated decline of aerobic capacity and may serve as clinically valuable prognostic indicators of cardiovascular health. We investigated the relationship between circulating ceramides and VO2 peak in 443 men and women (mean age of 69) enrolled in the Baltimore Longitudinal Study of Aging (BLSA)...
October 2016: Aging Cell
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