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https://www.readbyqxmd.com/read/28447569/a-new-treatment-strategy-for-parkinson-s-disease-through-the-gut-brain-axis-the-glucagon-like-peptide-1-receptor-pathway
#1
Dong Seok Kim, Ho-Il Choi, Yun Wang, Yu Luo, Barry J Hoffer, Nigel H Greig
Molecular communications in the gut-brain axis, between the central nervous system and the gastrointestinal tract, arecritical for maintaining healthy brain function particularly in aging. Epidemiological analyses indicate type 2 diabetes mellitus (T2DM) is a risk factor for neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's diseases (PD) for which aging shows a major correlative association. Common pathophysiological features exist between T2DM, AD and PD, including oxidative stress, inflammation, insulin resistance, abnormal protein processing and cognitive decline, and suggest that effective drugs for T2DM that positively impact the gut-brain axis could provide an effective treatment option for neurodegenerative diseases...
April 26, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28412449/targeted-drug-delivery-system-to-neural-cells-utilizes-the-nicotinic-acetylcholine-receptor
#2
Rachel Huey, Barry O'Hagan, Paul McCarron, Susan Hawthorne
Drug delivery to the brain is still a major challenge in the field of therapeutics, especially for large and hydrophilic compounds. In order to achieve drug delivery of therapeutic concentration in the central nervous system, the problematic blood brain barrier (BBB) must be overcome. This work presents the formulation of a targeted nanoparticle-based drug delivery system using a specific neural cell targeting ligand, rabies virus derived peptide (RDP). Characterization studies revealed that RDP could be conjugated to drug-loaded PLGA nanoparticles of average diameter 257...
April 12, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28395539/unlocking-the-box-basic-requirements-for-an-ideal-ventricular-assist-device-controller
#3
Alexander L Medvedev, Jamshid H Karimov, Barry D Kuban, David J Horvath, Nader Moazami, Kiyotaka Fukamachi
A modern ventricular assist device (VAD) system comprises an implantable rotary blood pump and external components located outside the patient's body: a wearable controller connected to the pump via a percutaneous cable, wearable rechargeable batteries, battery charger, alternating- and direct-current power supplies, and a hospital device to control and monitor the system. If the blood pump is the "heart" of a VAD system, the controller is its "brain." The controller drives the pump's electrical motor; varies the pump speed or flow based on user commands or feedback signals; collects, processes, and stores data; performs self-diagnostics; transmits to and receives data from other system components, i...
April 11, 2017: Expert Review of Medical Devices
https://www.readbyqxmd.com/read/28319499/developmental-venous-anomalies-mimicking-neoplasm-on-11c-methionine-pet-and-dsc-perfusion-mri
#4
Julie H Harreld, Mikhail Doubrovin, Elizabeth R Butch, Angela Edwards, Barry Shulkin
Elevated relative cerebral blood volume on perfusion MRI and increased uptake on C-methionine PET can be used to diagnose and guide biopsy of brain tumors but are not specific. We report increased uptake on C-methionine PET associated with 4 developmental venous anomalies (DVAs) in 3 children with brain tumors, which could potentially mimic tumor and misdirect biopsy. Because DVAs are not readily visible on CT, prevention of misdirected biopsy in patients with focally elevated C-methionine uptake and relative cerebral blood volume relies on close correlation with contrast-enhanced anatomic MRI to exclude DVA or other nonneoplastic etiology...
May 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28276534/non-invasive-assessment-of-cerebral-blood-flow-and-oxygen-metabolism-in-neonates-during-hypothermic-cardiopulmonary-bypass-feasibility-and-clinical-implications
#5
Silvina L Ferradal, Koichi Yuki, Rutvi Vyas, Christopher G Ha, Francesca Yi, Christian Stopp, David Wypij, Henry H Cheng, Jane W Newburger, Aditya K Kaza, Maria A Franceschini, Barry D Kussman, P Ellen Grant
The neonatal brain is extremely vulnerable to injury during periods of hypoxia and/or ischemia. Risk of brain injury is increased during neonatal cardiac surgery, where pre-existing hemodynamic instability and metabolic abnormalities are combined with long periods of low cerebral blood flow and/or circulatory arrest. Our understanding of events associated with cerebral hypoxia-ischemia during cardiopulmonary bypass (CPB) remains limited, largely due to inadequate tools to quantify cerebral oxygen delivery and consumption non-invasively and in real-time...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197303/optimization-of-3-pyrimidin-4-yl-oxazolidin-2-ones-as-allosteric-and-mutant-specific-inhibitors-of-idh1
#6
Julian R Levell, Thomas Caferro, Gregg Chenail, Ina Dix, Julia Dooley, Brant Firestone, Pascal D Fortin, John Giraldes, Ty Gould, Joseph D Growney, Michael D Jones, Raviraj Kulathila, Fallon Lin, Gang Liu, Arne Mueller, Simon van der Plas, Kelly Slocum, Troy Smith, Remi Terranova, B Barry Touré, Viraj Tyagi, Trixie Wagner, Xiaoling Xie, Ming Xu, Fan S Yang, Liping X Zhou, Raymond Pagliarini, Young Shin Cho
High throughput screening and subsequent hit validation identified 4-isopropyl-3-(2-((1-phenylethyl)amino)pyrimidin-4-yl)oxazolidin-2-one as a potent inhibitor of IDH1(R132H). Synthesis of the four separate stereoisomers identified the (S,S)-diastereomer (IDH125, 1f) as the most potent isomer. This also showed reasonable cellular activity and excellent selectivity vs IDH1(wt). Initial structure-activity relationship exploration identified the key tolerances and potential for optimization. X-ray crystallography identified a functionally relevant allosteric binding site amenable to inhibitors, which can penetrate the blood-brain barrier, and aided rational optimization...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28140493/cerebral-high-intensity-transient-signals-during-pediatric-cardiac-catheterization-a-pilot-study-using-transcranial-doppler-ultrasonography
#7
Kerri L LaRovere, Kush Kapur, Doff B McElhinney, Alexander Razumovsky, Barry D Kussman
BACKGROUND AND PURPOSE: Cerebral emboli are one potential cause of acute brain injury in children with congenital heart disease (CHD) undergoing cardiac catheterization. In this pilot study using transcranial Doppler (TCD) ultrasonography, we sought to evaluate the incidence, burden, and circumstances of cerebral high-intensity transient signals (HITS), presumably representing emboli, during pediatric cardiac catheterization. METHODS: Emboli monitoring of the right middle cerebral artery was performed in five children...
January 31, 2017: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/28139719/a-functional-il22-polymorphism-rs2227473-is-associated-with-predisposition-to-childhood-cerebral-malaria
#8
Sandrine Marquet, Ianina Conte, Belco Poudiougou, Laurent Argiro, Hélia Dessein, Charlène Couturier, Florence Burté, Aboubacar A Oumar, Biobele J Brown, Abdoualye Traore, Nathaniel K Afolabi, Abdoulaye Barry, Samuel Omokhodion, Wuraola A Shokunbi, Olugbemiro Sodeinde, Ogobara Doumbo, Delmiro Fernandez-Reyes, Alain J Dessein
Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection. This encephalopathy is characterized by coma and is thought to result from mechanical microvessel obstruction and an excessive activation of immune cells leading to pathological inflammation and blood-brain barrier alterations. IL-22 contributes to both chronic inflammatory and infectious diseases, and may have protective or pathogenic effects, depending on the tissue and disease state. We evaluated whether polymorphisms (n = 46) of IL22 and IL22RA2 were associated with CM in children from Nigeria and Mali...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27553758/hmgb1-and-thrombin-mediate-the-blood-brain-barrier-dysfunction-acting-as-biomarkers-of-neuroinflammation-and-progression-to-neurodegeneration-in-alzheimer-s-disease
#9
Barry W Festoff, Ravi K Sajja, Patrick van Dreden, Luca Cucullo
BACKGROUND: The blood-brain barrier (BBB) dysfunction represents an early feature of Alzheimer's disease (AD) that precedes the hallmarks of amyloid beta (amyloid β) plaque deposition and neuronal neurofibrillary tangle (NFT) formation. A damaged BBB correlates directly with neuroinflammation involving microglial activation and reactive astrogliosis, which is associated with increased expression and/or release of high-mobility group box protein 1 (HMGB1) and thrombin. However, the link between the presence of these molecules, BBB damage, and progression to neurodegeneration in AD is still elusive...
2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27342958/apol1-renal-risk-variants-associate-with-reduced-cerebral-white-matter-lesion-volume-and-increased-gray-matter-volume
#10
Barry I Freedman, Crystal A Gadegbeku, R Nick Bryan, Nicholette D Palmer, Pamela J Hicks, Lijun Ma, Michael V Rocco, S Carrie Smith, Jianzhao Xu, Christopher T Whitlow, Benjamin C Wagner, Carl D Langefeld, Amret T Hawfield, Jeffrey T Bates, Alan J Lerner, Dominic S Raj, Mohammad S Sadaghiani, Robert D Toto, Jackson T Wright, Donald W Bowden, Jeff D Williamson, Kaycee M Sink, Joseph A Maldjian, Nicholas M Pajewski, Jasmin Divers
To assess apolipoprotein L1 gene (APOL1) renal-risk-variant effects on the brain, magnetic resonance imaging (MRI)-based cerebral volumes and cognitive function were assessed in 517 African American-Diabetes Heart Study (AA-DHS) Memory IN Diabetes (MIND) and 2568 hypertensive African American Systolic Blood Pressure Intervention Trial (SPRINT) participants without diabetes. Within these cohorts, 483 and 197 had cerebral MRI, respectively. AA-DHS participants were characterized as follows: 60.9% female, mean age of 58...
August 2016: Kidney International
https://www.readbyqxmd.com/read/27325686/st-11-a-new-brain-penetrant-microtubule-destabilizing-agent-with-therapeutic-potential-for-glioblastoma-multiforme
#11
Allison E Cherry, Brian R Haas, Alipi V Naydenov, Susan Fung, Cong Xu, Katie Swinney, Michael Wagenbach, Jennifer Freeling, David A Canton, Jonathan Coy, Eric A Horne, Barry Rickman, Juan Jesus Vicente, John D Scott, Rodney J Y Ho, Denny Liggitt, Linda Wordeman, Nephi Stella
Glioblastoma multiforme is a devastating and intractable type of cancer. Current antineoplastic drugs do not improve the median survival of patients diagnosed with glioblastoma multiforme beyond 14 to 15 months, in part because the blood-brain barrier is generally impermeable to many therapeutic agents. Drugs that target microtubules (MT) have shown remarkable efficacy in a variety of cancers, yet their use as glioblastoma multiforme treatments has also been hindered by the scarcity of brain-penetrant MT-targeting compounds...
September 2016: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27247960/behavioral-and-transcriptomic-profiling-of-mice-null-for-lphn3-a-gene-implicated-in-adhd-and-addiction
#12
Caitlin A Orsini, Barry Setlow, Michael DeJesus, Stacy Galaviz, Kimberly Loesch, Thomas Ioerger, Deeann Wallis
BACKGROUND: The Latrophilin 3 (LPHN3) gene (recently renamed Adhesion G protein-coupled receptor L3 (ADGRL3)) has been linked to susceptibility to attention deficit/hyperactivity disorder (ADHD) and vulnerability to addiction. However, its role and function are not well understood as there are no known functional variants. METHODS: To characterize the function of this little known gene, we phenotyped Lphn3 null mice. We assessed motivation for food reward and working memory via instrumental responding tasks, motor coordination via rotarod, and depressive-like behavior via forced swim...
May 2016: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/27154855/active-rehabilitation-of-concussion-and-post-concussion-syndrome
#13
REVIEW
John J Leddy, John G Baker, Barry Willer
Concussion is a physiological brain injury with physical, cognitive, and emotional sequelae. The macrophysiological insult to the brain affects the autonomic nervous system and its control of cerebral blood flow. Most patients recover within 2 weeks, but some do not. Persistence of symptoms beyond the generally accepted time frame for recovery is called post-concussion syndrome (PCS). PCS is not a single entity; it is a group of disorders that requires specific forms of therapy. Rest has been the mainstay of the treatment for concussion and PCS...
May 2016: Physical Medicine and Rehabilitation Clinics of North America
https://www.readbyqxmd.com/read/27149521/a-susceptible-mouse-model-for-zika-virus-infection
#14
Stuart D Dowall, Victoria A Graham, Emma Rayner, Barry Atkinson, Graham Hall, Robert J Watson, Andrew Bosworth, Laura C Bonney, Samantha Kitchen, Roger Hewson
Zika virus (ZIKV) is a mosquito-borne pathogen which has recently spread beyond Africa and into Pacific and South American regions. Despite first being detected in 1947, very little information is known about the virus, and its spread has been associated with increases in Guillain-Barre syndrome and microcephaly. There are currently no known vaccines or antivirals against ZIKV infection. Progress in assessing interventions will require the development of animal models to test efficacies; however, there are only limited reports on in vivo studies...
May 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27039129/use-of-high-sensitivity-troponin-t-to-identify%C3%A2-patients-with-acute-heart-failure-at%C3%A2-lower%C3%A2-risk-for-adverse-outcomes-an-exploratory-analysis-from-the-relax-ahf-trial
#15
Peter S Pang, John R Teerlink, Adriaan A Voors, Piotr Ponikowski, Barry H Greenberg, Gerasimos Filippatos, G Michael Felker, Beth A Davison, Gad Cotter, Joshua Kriger, Margaret F Prescott, Tsushung A Hua, Thomas Severin, Marco Metra
OBJECTIVES: The aim of this study was to determine if a baseline high-sensitivity troponin T (hsTnT) value ≤99th percentile upper reference limit (0.014 μg/l ["low hsTnT"]) identifies patients at low risk for adverse outcomes. BACKGROUND: Approximately 85% of patients who present to emergency departments with acute heart failure are admitted. Identification of patients at low risk might decrease unnecessary admissions. METHODS: A post-hoc analysis was conducted from the RELAX-AHF (Serelaxin, Recombinant Human Relaxin-2, for Treatment of Acute Heart Failure) trial, which randomized patients within 16 h of presentation who had systolic blood pressure >125 mm Hg, mild to moderate renal impairment, and N-terminal pro-brain natriuretic peptide ≥1,600 ng/l to serelaxin versus placebo...
July 2016: JACC. Heart Failure
https://www.readbyqxmd.com/read/26997298/the-psychoactive-designer-drug-and-bath-salt-constituent-mdpv-causes-widespread-disruption-of-brain-functional-connectivity
#16
Luis M Colon-Perez, Kelvin Tran, Khalil Thompson, Michael C Pace, Kenneth Blum, Bruce A Goldberger, Mark S Gold, Adriaan W Bruijnzeel, Barry Setlow, Marcelo Febo
The abuse of 'bath salts' has raised concerns because of their adverse effects, which include delirium, violent behavior, and suicide ideation in severe cases. The bath salt constituent 3,4-methylenedioxypyrovalerone (MDPV) has been closely linked to these and other adverse effects. The abnormal behavioral pattern produced by acute high-dose MDPV intake suggests possible disruptions of neural communication between brain regions. Therefore, we determined if MDPV exerts disruptive effects on brain functional connectivity, particularly in areas of the prefrontal cortex...
August 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/26975495/quantitative-measurement-of-blood-flow-in-paediatric-brain-tumours-a-comparative-study-of-dynamic-susceptibility-contrast-and-multi-time-point-arterial-spin-labelled-mri
#17
Rishma Vidyasagar, Laurence Abernethy, Barry Pizer, Shivaram Avula, Laura M Parkes
OBJECTIVE: Arterial spin-labelling (ASL) MRI uses intrinsic blood water to quantify the cerebral blood flow (CBF), removing the need for the injection of a gadolinium-based contrast agent used for conventional perfusion imaging such as dynamic susceptibility contrast (DSC). Owing to the non-invasive nature of the technique, ASL is an attractive option for use in paediatric patients. This work compared DSC and multi-timepoint ASL measures of CBF in paediatric brain tumours. METHODS: Patients (n = 23; 20 low-grade tumours and 3 high-grade tumours) had DSC and multi-timepoint ASL with and without vascular crushers (VC)...
June 2016: British Journal of Radiology
https://www.readbyqxmd.com/read/26944489/neck-length-and-mean-arterial-pressure-in-the-sauropod-dinosaurs
#18
Stephen Hughes, John Barry, Jeremy Russell, Robert Bell, Som Gurung
How blood was able to reach the heads of the long-necked sauropod dinosaurs has long been a matter of debate and several hypotheses have been presented. For example, it has been proposed that sauropods had exceptionally large hearts, multiple 'normal' sized hearts spaced at regular intervals up the neck or held their necks horizontal, or that the siphon effect was in operation. By means of an experimental model, we demonstrate that the siphon principle is able to explain how blood was able to adequately perfuse the sauropod brain...
April 15, 2016: Journal of Experimental Biology
https://www.readbyqxmd.com/read/26700867/comparative-clinico-pathological-observations-in-young-zebu-bos-indicus-cattle-experimentally-infected-with-trypanosoma-vivax-isolates-from-tsetse-infested-and-non-tsetse-areas-of-northwest-ethiopia
#19
Shimelis Dagnachew, Getachew Terefe, Getachew Abebe, Asegedech Sirak, Enrico Bollo, Dave Barry, Bruno Goddeeris
BACKGROUND: The Northwest region of Ethiopia is affected by both tsetse and non-tsetse transmitted trypanosomosis with a huge impact on livestock productivity. The objective of this experimental study was to determine clinical and pathological findings in young Zebu cattle experimentally infected with Trypanosoma vivax isolates from tsetse infested and non-tsetse infested areas of Northwest Ethiopia. A total of 18 cattle (Bos indicus) aged between 6 and 12 months, purchased from a trypanosome-free and confirmed to be trypanosome negative divided into three groups of six animals were used...
2015: BMC Veterinary Research
https://www.readbyqxmd.com/read/26670617/hydroxycarbamide-versus-chronic-transfusion-for-maintenance-of-transcranial-doppler-flow-velocities-in-children-with-sickle-cell-anaemia-tcd-with-transfusions-changing-to-hydroxyurea-twitch-a-multicentre-open-label-phase-3-non-inferiority-trial
#20
RANDOMIZED CONTROLLED TRIAL
Russell E Ware, Barry R Davis, William H Schultz, R Clark Brown, Banu Aygun, Sharada Sarnaik, Isaac Odame, Beng Fuh, Alex George, William Owen, Lori Luchtman-Jones, Zora R Rogers, Lee Hilliard, Cynthia Gauger, Connie Piccone, Margaret T Lee, Janet L Kwiatkowski, Sherron Jackson, Scott T Miller, Carla Roberts, Matthew M Heeney, Theodosia A Kalfa, Stephen Nelson, Hamayun Imran, Kerri Nottage, Ofelia Alvarez, Melissa Rhodes, Alexis A Thompson, Jennifer A Rothman, Kathleen J Helton, Donna Roberts, Jamie Coleman, Melanie J Bonner, Abdullah Kutlar, Niren Patel, John Wood, Linda Piller, Peng Wei, Judy Luden, Nicole A Mortier, Susan E Stuber, Naomi L C Luban, Alan R Cohen, Sara Pressel, Robert J Adams
BACKGROUND: For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions. METHODS: TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada...
February 13, 2016: Lancet
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