Medicine and Health Sciences Commons^™

Better Cognitive Control Of Emotional Information Is Associated With Reduced Pro-Inflammatory Cytokine Reactivity To Emotional Stress, Grant S. Shields, Shari Young Kuchenbecker, Sarah D. Pressman, Ken D. Sumida, George M. Slavich

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Stress is strongly associated with several mental and physical health problems that involve inflammation, including asthma, cardiovascular disease, certain types of cancer, and depression. It has been hypothesized that better cognitive control of emotional information may lead to reduced inflammatory reactivity to stress and thus better health, but to date no studies have examined whether differences in cognitive control predict pro-inflammatory cytokine responses to stress. To address this issue, we conducted a laboratory-based experimental study in which we randomly assigned healthy young-adult females to either an acute emotional stress (emotionally evocative video) or no-stress (control video) condition. Salivary levels of …

Pharmaceutical Integrated Stress Response Enhancement Protects Oligodendrocytes And Provides A Potential Multiple Sclerosis Therapeutic., Sharon W Way, Joseph R Podojil, Benjamin L Clayton, Anita Zaremba, Tassie L Collins, Rejani B Kunjamma, Andrew P Robinson, Pedro Brugarolas, Robert H. Miller, Stephen D Miller, Brian Popko

Anatomy and Regenerative Biology Faculty Publications

Oligodendrocyte death contributes to the pathogenesis of the inflammatory demyelinating disease multiple sclerosis (MS). Nevertheless, current MS therapies are mainly immunomodulatory and have demonstrated limited ability to inhibit MS progression. Protection of oligodendrocytes is therefore a desirable strategy for alleviating disease. Here we demonstrate that enhancement of the integrated stress response using the FDA-approved drug guanabenz increases oligodendrocyte survival in culture and prevents hypomyelination in cerebellar explants in the presence of interferon-γ, a pro-inflammatory cytokine implicated in MS pathogenesis. In vivo, guanabenz treatment protects against oligodendrocyte loss caused by CNS-specific expression of interferon-γ. In a mouse model of MS, experimental …

Specific Increase In Mdr1 Mediated Drug-Efflux In Human Brain Endothelial Cells Following Co-Exposure To Hiv-1 And Saquinavir, Upal Roy, Christine Bulot, Kerstin Honer Zu Bentrup, Debasis Mondal

HWCOM Faculty Publications

Persistence of HIV-1 reservoirs within the Central Nervous System (CNS) remains a significant challenge to the efficacy of potent anti-HIV-1 drugs. The primary human Brain Microvascular Endothelial Cells (HBMVEC) constitutes the Blood Brain Barrier (BBB) which interferes with anti-HIV drug delivery into the CNS. The ATP binding cassette (ABC) transporters expressed on HBMVEC can efflux HIV-1 protease inhibitors (HPI), enabling the persistence of HIV-1 in CNS. Constitutive low level expression of several ABC-transporters, such as MDR1 (a.k.a. P-gp) and MRPs are documented in HBMVEC. Although it is recognized that inflammatory cytokines and exposure to xenobiotic drug substrates (e.g HPI) can …

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, …

Linking Obesity To Colorectal Cancer: Recent Insights Into Plausible Biological Mechanisms, Catherine Guffey

Theses and Dissertations

Obesity has emerged as a leading environmental risk factor for the development of CRC. However, the mechanisms underlying this relationship have not yet been fully explained. Recent literature has focused on 1) inflammatory processes, 2) adipokines, and 3) estrogen. Obesity-enhanced inflammation is largely orchestrated by increases in adipose tissue macrophages leading to the secretion of TNF-alpha, MCP-1, and IL-6, all of which are linked to CRC. Adiponectin is decreased with obesity and has been reported to be negatively associated with CRC, while leptin, which is increased, is positively associated with the disease. Estrogen has been shown to influence CRC, although …

Compound 49b: A Novel Beta-Adrenergic Receptor Agonist In The Treatment Of Diabetic Retinopathy, Kimberly Williams-Guy

Theses and Dissertations (ETD)

Diabetic retinopathy is the leading cause of blindness in working Americans. While there are therapeutic regimens for the disease, more effective methods are needed. We have previously shown that a non-specific beta-adrenergic receptor agonist, isoproterenol, was effective in preventing functional and morphological changes associated with diabetic retinopathy in the rat. Isoproterenol also produced left ventricle remodeling suggesting it entered the systemic circulation. We therefore synthesized various novel beta-adrenergic receptor compounds and screened these compounds in vitro for their ability to reduce markers of inflammation and apoptosis. Of the various compounds tested, Compound 49b was able to reduce both inflammation and …

Synthesis And In Vitro Binding Of N,N-Dialkyl-2-Phenylindol-3-Ylglyoxylamides For The Peripheral Benzodiazepine Binding Sites, T. P. Homes, F. Mattner, Paul A. Keller, A. Katsifis

Paul Keller

A series of N,N-dialkyl-2-phenylindol-3-ylglyoxylamides bearing the halogens iodine and bromine were synthesised and their binding affinity for the peripheral benzodiazepine binding sites (PBBS) in rat kidney mitochondrial membranes were evaluated using [3H]-PK11195. Central benzodiazepine receptor (CBR) affinities were also evaluated in rat cortices using 3H-flumazenil to determine their selectivity for PBBS over CBR. The tested compounds had PBBS binding affinities (IC50) ranging from 7.86 nM to 618 nM, with all compounds showing high selectivity over the CBR (CBR IC50 > 5000 nM). Among the 12 compounds tested, those with a diethylamide group were the most potent. The highest affinity iodinated PBBS …

Synthesis And In Vitro Binding Of N,N-Dialkyl-2-Phenylindol-3-Ylglyoxylamides For The Peripheral Benzodiazepine Binding Sites, T. P. Homes, F. Mattner, Paul A. Keller, A. Katsifis

Faculty of Science - Papers (Archive)

A series of N,N-dialkyl-2-phenylindol-3-ylglyoxylamides bearing the halogens iodine and bromine were synthesised and their binding affinity for the peripheral benzodiazepine binding sites (PBBS) in rat kidney mitochondrial membranes were evaluated using [3H]-PK11195. Central benzodiazepine receptor (CBR) affinities were also evaluated in rat cortices using 3H-flumazenil to determine their selectivity for PBBS over CBR. The tested compounds had PBBS binding affinities (IC50) ranging from 7.86 nM to 618 nM, with all compounds showing high selectivity over the CBR (CBR IC50 > 5000 nM). Among the 12 compounds tested, those with a diethylamide group were the most potent. The highest affinity iodinated PBBS …