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https://www.readbyqxmd.com/read/28446518/glutaminyl-cyclase-inhibitor-pq912-improves-cognition-in-mouse-models-of-alzheimer-s-disease-studies-on-relation-to-effective-target-occupancy
#1
Torsten Hoffmann, Antje Meyer, Ulrich Heiser, Stephan Kurat, Livia Bohme, Martin Kleinschmidt, Karl-Ulrich Buhring, Birgit Hutter-Paier, Martina Farcher, Hans-Ulrich Demuth, Inge Lues, Stephan Schilling
Numerous studies suggest that the majority of Aβ peptides deposited in Alzheimer's Disease (AD) is truncated and post-translationally modified at the N-terminus. Among these modified species, pyroglutamyl-Aβ (pE-Aβ including N3pE-Aβ42) has been identified as particularly neurotoxic. The N-terminal modification renders the peptide hydrophobic, accelerates formation of oligomers and reduces degradation by peptidases leading ultimately to the accumulation of the peptide and progression of AD. It has been shown, that the formation of pyroglutamyl residues is catalysed by glutaminyl cyclase (QC)...
April 26, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28445178/familial-hemiplegic-migraine-with-asymmetric-encephalopathy-secondary-to-atp1a2-mutation-a-case-series
#2
Olwen C Murphy, Aine Merwick, Olivia OʼMahony, Aisling M Ryan, Brian McNamara
INTRODUCTION: Familial hemiplegic migraine (FHM) is a genetic disease with a variable clinical phenotype. The imaging and electroencephalogram (EEG) correlates of FHM are not well described. CASE SERIES: We describe a case series of five young women aged 12 to 32 years. Each case presented with headache, encephalopathy, and hemiparesis of varying severity. One patient developed seizures. All patients improved spontaneously. INVESTIGATIONS: Asymmetric slow-wave activity was seen on electroencephalogram in each case...
April 25, 2017: Journal of Clinical Neurophysiology: Official Publication of the American Electroencephalographic Society
https://www.readbyqxmd.com/read/28440309/glypican-2-levels-in-cerebrospinal-fluid-predict-the-status-of-adult-hippocampal-neurogenesis
#3
S Lugert, T Kremer, R Jagasia, A Herrmann, S Aigner, C Giachino, I Mendez-David, A M Gardier, J P Carralot, H Meistermann, A Augustin, M D Saxe, J Lamerz, G Duran-Pacheco, A Ducret, V Taylor, D J David, C Czech
Adult hippocampal neurogenesis is a remarkable form of brain plasticity through which new neurons are generated throughout life. Despite its important roles in cognition and emotion and its modulation in various preclinical disease models, the functional importance of adult hippocampal neurogenesis in human health has not been revealed because of a lack of tools for monitoring adult neurogenesis in vivo. Therefore, we performed an unbiased proteomics screen to identify novel proteins expressed during neuronal differentiation using a human neural stem cell model, and we identified the proteoglycan Glypican-2 (Gpc2) as a putative secreted marker of immature neurons...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28427941/elongation-affinity-activation-barrier-and-stability-of-a%C3%AE-42-oligomers-fibrils-in-physiological-saline
#4
Roberto A Rodriguez, Liao Y Chen, Germán Plascencia-Villa, George Perry
Amyloid-beta (Aβ) peptides, Aβ40 and the more neurotoxic Aβ42, have been the subject of many research efforts for Alzheimer's disease. In two recent independent investigations, the atomistic structure of Aβ42 fibril has been clearly established in the S-shaped conformation consisting of three β-sheets stabilized by salt bridges formed between the Lys28 sidechain and the C-terminus of Ala42. This structure distinctively differs from the long-known structure of Aβ40 in the β-hairpin shaped conformation consisting of two β-sheets...
April 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28403108/analyses-and-treatments-of-postoperative-nasal-complications-after-endonasal-transsphenoidal-resection-of-pituitary-neoplasms
#5
You Cheng, Fei Xue, Tian-You Wang, Jun-Feng Ji, Wei Chen, Zhi-Yi Wang, Li Xu, Chun-Hua Hang, Xin-Feng Liu
In this study, we analyze and discuss the treatments of postoperative nasal complications after endonasal transsphenoidal resection of pituitary neoplasms (PNs). We performed 129 endonasal transsphenoidal resections of PNs and analyzed and treated cases with nasal complications. After endonasal transsphenoidal resection of PNs, there were 26 cases of postoperative nasal complications (20.1%), including nasal hemorrhage (4.8%), cerebrospinal fluid rhinorrhea (6.9%), sphenoid sinusitis (2.3%), atrophic rhinitis (1...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28380662/involvement-of-intracellular-zn-2-signaling-in-ltp-at-perforant-pathway-ca1-pyramidal-cell-synapse
#6
Haruna Tamano, Ryusuke Nishio, Atsushi Takeda
Physiological significance of synaptic Zn(2+) signaling was examined at perforant pathway-CA1 pyramidal cell synapses. In vivo long-term potentiation (LTP) at perforant pathway-CA1 pyramidal cell synapses was induced using a recording electrode attached to a microdialysis probe and the recording region was locally perfused with artificial cerebrospinal fluid (ACSF) via the microdialysis probe. Perforant pathway LTP was not attenuated under perfusion with CaEDTA (10 mM), an extracellular Zn(2+) chelator, but attenuated under perfusion with ZnAF-2DA (50 μM), an intracellular Zn(2+) chelator, suggesting that intracellular Zn(2+) signaling is required for perforant pathway LTP...
April 5, 2017: Hippocampus
https://www.readbyqxmd.com/read/28370852/prospective-study-of-the-use-of-intraoperative-neuromonitoring-in-determining-post-operative-energy-requirements-and-physiologic-midline-in-spinal-cord-stimulation
#7
Claire Collison, Julia Prusik, Steven Paniccioli, Michael Briotte, Rachael Grey, Paul Feustel, Julie G Pilitsis
BACKGROUND: Intraoperative neuromonitoring (IONM) through electromyography (EMG) studies has been shown to be a safe, effective way to determine the laterality of the spinal cord and guide electrode placement during spinal cord stimulation (SCS). However, the use of IONM to predict post-operative energy requirements and midline has not been examined and offers a new avenue to streamline programming and device selection. Further, the impact of cerebrospinal fluid (CSF) thickness on intraoperative and post-operative amplitudes is understood but has not been explicitly characterized...
March 28, 2017: Neuromodulation: Journal of the International Neuromodulation Society
https://www.readbyqxmd.com/read/28365894/gene-expression-analysis-and-microdialysis-suggest-hypothalamic-triiodothyronine-t3-gates-daily-torpor-in-djungarian-hamsters-phodopus-sungorus
#8
Jonathan H H Bank, Ceyda Cubuk, Dana Wilson, Eddy Rijntjes, Julia Kemmling, Hanna Markovsky, Perry Barrett, Annika Herwig
Thyroid hormones play an important role in regulating seasonal adaptations of mammals. Several studies suggested that reduced availability of 3,3',5-triiodothyronine (T3) in the hypothalamus is required for the physiological adaptation to winter in Djungarian hamsters. We have previously shown that T3 is involved in the regulation of daily torpor, but it remains unclear, whether T3 affects torpor by central or peripheral mechanisms. To determine the effect of T3 concentrations within the hypothalamus in regulating daily torpor, we tested the hypothesis that low hypothalamic T3 metabolism would favour torpor and high T3 concentrations would not...
April 1, 2017: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
https://www.readbyqxmd.com/read/28344983/effects-of-bile-acids-on-human-airway-epithelial-cells-implications-for-aerodigestive-diseases
#9
Adil Aldhahrani, Bernard Verdon, Chris Ward, Jeffery Pearson
Gastro-oesophageal reflux and aspiration have been associated with chronic and end-stage lung disease and with allograft injury following lung transplantation. This raises the possibility that bile acids may cause lung injury by damaging airway epithelium. The aim of this study was to investigate the effect of bile acid challenge using the immortalised human bronchial epithelial cell line (BEAS-2B). The immortalised human bronchial epithelial cell line (BEAS-2B) was cultured. A 48-h challenge evaluated the effect of individual primary and secondary bile acids...
January 2017: ERJ Open Research
https://www.readbyqxmd.com/read/28343338/expression-of-typical-osteoclast-markers-by-pbmcs-after-peg-induced-fusion-as-a-model-for-studying-osteoclast-differentiation
#10
Luz M Castillo, Carlos A Guerrero, Orlando Acosta
Bone is a metabolically active organ subjected to continuous remodeling process that involves resorption by osteoclast and subsequent formation by osteoblasts. Osteoclast involvement in this physiological event is regulated by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). Fusion of mono-nuclear pre-osteoclasts is a critical event for osteoclast differentiation and for bone resorption. Here we show that PBMCs can be successfully fused with polyethylenglicol (PEG) in order to generated viable osteoclast-like cells that exhibit tartrate-resistant acid phosphatase (TRAP) and bone resorptive activities...
March 25, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/28340601/rantes-levels-in-peripheral-blood-csf-and-contused-brain-tissue-as-a-marker-for-outcome-in-traumatic-brain-injury-tbi-patients
#11
Venencia Albert, Arulselvi Subramanian, Deepak Agrawal, Sanjeev Kumar Bhoi, Pooja Pallavi, A K Mukhopadhayay
BACKGROUND: Traumatic brain injury (TBI) causes activation of several neurochemical and physiological cascades, leading to neurological impairment. We aimed to investigate the level of novel chemokine RANTES in plasma, cerebrospinal fluid (CSF) and contused brain tissue in traumatic brain injury patients and to correlate the expression of this chemokine with the severity of head injury and neurological outcome. METHODS: This longitudinal case control study was performed on 70 TBI patients over a period of 30 months...
March 24, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28337665/effect-of-efflux-transporter-inhibition-on-the-distribution-of-fluconazole-in-the-rat-brain
#12
Wei Wang, Na Zheng, Jiatang Zhang, Xusheng Huang, Shengyuan Yu
Multidrug resistance-associated proteins (MRPs) and organic anion transporters (OATs) are expressed on the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB), preventing the entry of or the pumping out of numerous molecules. Fluconazole is widely used to treat fungal meningoencephalitis. The effect of these transporters on the distribution of fluconazole in the brain is unclear. We used microdialysis to compare the distribution of fluconazole in the rat brain with and without co-administration of probenecid, a MRP and OAT inhibitor...
March 24, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28330873/amp-activated-protein-kinase-%C3%AE-1-promotes-atherogenesis-by-increasing-monocyte-to-macrophage-differentiation
#13
Miao Zhang, Huaiping Zhu, Ye Ding, Zhaoyu Liu, Zhejun Cai, Ming-Hui Zou
Monocyte-to-macrophage differentiation, which can be initiated by physiological or atherogenic factors, is a pivotal process in atherogenesis, a disorder in which monocytes adhere to endothelial cells and subsequently migrate into the sub-endothelial spaces, where they differentiate into macrophages and macrophage-derived foam cells and cause atherosclerotic lesions. However, the monocyte-differentiation signaling pathways that are activated by atherogenic factors are poorly defined. Here we report that the AMP- activated protein kinase (AMPK) α1 in monocytes promotes atherosclerosis by increasing monocyte differentiation and survival...
March 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28330845/transport-across-the-choroid-plexus-epithelium
#14
Jeppe Praetorius, Helle Hasager Damkier
The choroid plexus epithelium is a secretory epithelium par excellence. However, this is perhaps not the most prominent reason for the massive interest in this modest-sized tissue residing inside the brain ventricles. Most likely, the dominant reason for extensive studies of the choroid plexus is the identification of this epithelium as the source of the majority of intraventricular cerebrospinal fluid. This finding has direct relevance for studies of diseases and conditions with deranged central fluid volume or ionic balance...
March 22, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28325760/neisseria-meningitidis-uses-sibling-small-regulatory-rnas-to-switch-from-cataplerotic-to-anaplerotic-metabolism
#15
Yvonne Pannekoek, Robert A G Huis In 't Veld, Kim Schipper, Sandra Bovenkerk, Gertjan Kramer, Matthijs C Brouwer, Diederik van de Beek, Dave Speijer, Arie van der Ende
Neisseria meningitidis (the meningococcus) is primarily a commensal of the human oropharynx that sporadically causes septicemia and meningitis. Meningococci adapt to diverse local host conditions differing in nutrient supply, like the nasopharynx, blood, and cerebrospinal fluid, by changing metabolism and protein repertoire. However, regulatory transcription factors and two-component systems in meningococci involved in adaptation to local nutrient variations are limited. We identified novel sibling small regulatory RNAs ( Neisseriametabolic switch regulators [NmsRs]) regulating switches between cataplerotic and anaplerotic metabolism in this pathogen...
March 21, 2017: MBio
https://www.readbyqxmd.com/read/28300644/the-connective-tissue-phenotype-of-glaucomatous-cupping-in-the-monkey-eye-clinical-and-research-implications
#16
REVIEW
Hongli Yang, Juan Reynaud, Howard Lockwood, Galen Williams, Christy Hardin, Luke Reyes, Cheri Stowell, Stuart K Gardiner, Claude F Burgoyne
In a series of previous publications we have proposed a framework for conceptualizing the optic nerve head (ONH) as a biomechanical structure. That framework proposes important roles for intraocular pressure (IOP), IOP-related stress and strain, cerebrospinal fluid pressure (CSFp), systemic and ocular determinants of blood flow, inflammation, auto-immunity, genetics, and other non-IOP related risk factors in the physiology of ONH aging and the pathophysiology of glaucomatous damage to the ONH. The present report summarizes 20 years of technique development and study results pertinent to the characterization of ONH connective tissue deformation and remodeling in the unilateral monkey experimental glaucoma (EG) model...
March 12, 2017: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/28296283/effects-of-transendocardial-cd34-cell-transplantation-on-diastolic-parameters-in-patients-with-nonischemic-dilated-cardiomyopathy
#17
Mojca Bervar, Mirta Kozelj, Gregor Poglajen, Matjaz Sever, Gregor Zemljic, Sabina Frljak, Marko Cukjati, Peter Cernelc, François Haddad, Bojan Vrtovec
We sought to evaluate the physiological background and the effects of CD34(+) cell transplantation on diastolic parameters in nonischemic dilated cardiomyopathy patients (DCM). We enrolled 38 DCM patients with NYHA class III and LVEF <40% who underwent transendocardial CD34(+) cell transplantation. Peripheral blood CD34(+) cells were mobilized by G-CSF, collected via apheresis, and injected transendocardially in the areas of myocardial hibernation. Patients were followed for 1 year. At baseline, estimated filling pressures were significantly elevated (E/e'≥15) in 18 patients (Group A), and moderately elevated (E/e'<15) in 20 patients (Group B)...
March 11, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28292683/lower-inflammatory-markers-in-women-with-antenatal-depression-brings-the-m1-m2-balance-into-focus-from-a-new-direction
#18
Åsa Edvinsson, Emma Bränn, Charlotte Hellgren, Eva Freyhult, Richard White, Masood Kamali-Moghaddam, Jocelien Olivier, Jonas Bergquist, Adrian E Boström, Helgi B Schiöth, Alkistis Skalkidou, Janet L Cunningham, Inger Sundström-Poromaa
BACKGROUND: Antenatal depression and use of serotonin reuptake inhibitors (SSRI) in pregnancy have both been associated with an increased risk of poor pregnancy outcomes, such as preterm birth and impaired fetal growth. While the underlying biological pathways for these complications are poorly understood, it has been hypothesized that inflammation may be a common physiological pathway. The aim of the present study was to assess peripheral inflammatory markers in healthy women, women with antenatal depression, and in women using SSRI during pregnancy...
February 28, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28273770/transglutaminase-6-is-an-autoantigen-in-progressive-multiple-sclerosis-and-is-upregulated-in-reactive-astrocytes
#19
Massimiliano Cristofanilli, Daniel Gratch, Benjamin Pagano, Kelsey McDermott, Jessie Huang, Jeffrey Jian, Deneb Bates, Saud A Sadiq
BACKGROUND: Transglutaminase-6 (TGM6), a member of the transglutaminase enzyme family, is found predominantly in central nervous system (CNS) neurons under physiological conditions. It has been proposed as an autoimmune target in cerebral palsy, gluten-sensitive cerebellar ataxia, and schizophrenia. OBJECTIVE: To investigate TGM6 involvement in multiple sclerosis (MS). METHODS: Antibody levels against TGM6 (TGM6-IgG) were measured in the cerebrospinal fluid (CSF) of 62 primary progressive multiple sclerosis (PPMS), 85 secondary progressive multiple sclerosis (SPMS), and 50 relapsing-remitting multiple sclerosis (RRMS) patients and 51 controls...
December 1, 2016: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28243999/physiological-effects-of-early-incremental-mobilization-of-a-patient-with-acute-intracerebral-and-intraventricular-hemorrhage-requiring-dual-external-ventricular-drainage
#20
Sowmya Kumble, Elizabeth K Zink, Mackenzie Burch, Sandra Deluzio, Robert D Stevens, Mona N Bahouth
BACKGROUND: Recent trials have challenged the notion that very early mobility benefits patients with acute stroke. It is unclear how cerebral autoregulatory impairments, prevalent in this population, could be affected by mobilization. The safety of mobilizing patients who have external ventricular drainage (EVD) devices for cerebrospinal fluid diversion and intracranial pressure (ICP) monitoring is another concern due to risk of device dislodgment and potential elevation in ICP. We report hemodynamic and ICP responses during progressive, device-assisted mobility interventions performed in a critically ill patient with intracerebral hemorrhage (ICH) requiring two EVDs...
February 27, 2017: Neurocritical Care
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