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https://www.readbyqxmd.com/read/28918138/characterizing-effects-of-feed-restriction-and-glucagon-like-peptide-2-administration-on-biomarkers-of-inflammation-and-intestinal-morphology
#1
S K Kvidera, E A Horst, M V Sanz Fernandez, M Abuajamieh, S Ganesan, P J Gorden, H B Green, K M Schoenberg, W E Trout, A F Keating, L H Baumgard
Inadequate feed consumption reduces intestinal barrier function in both ruminants and monogastrics. Objectives were to characterize how progressive feed restriction (FR) affects inflammation, metabolism, and intestinal morphology, and to investigate if glucagon-like peptide 2 (GLP2) administration influences the aforementioned responses. Twenty-eight Holstein cows (157 ± 9 d in milk) were enrolled in 2 experimental periods. Period 1 [5 d of ad libitum (AL) feed intake] served as baseline for period 2 (5 d), during which cows received 1 of 6 treatments: (1) 100% of AL feed intake (AL100; n = 3), (2) 80% of AL feed intake (n = 5), (3) 60% of AL feed intake (n = 5), (4) 40% of AL feed intake (AL40; n = 5), (5) 40% of AL feed intake + GLP2 administration (AL40G; 75 µg/kg of BW s...
September 13, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28914134/blunted-cerebrovascular-response-is-associated-with-elevated-beta-amyloid
#2
Jason-Flor V Sisante, Eric D Vidoni, Kiersten Kirkendoll, Jaimie Ward, Yumei Liu, Sarah Kwapiszeski, Rebecca Maletsky, Jeffrey M Burns, Sandra A Billinger
The goal of this study was to explore the association of beta-amyloid accumulation and cerebrovascular response (CVR) in cognitively normal older adults. Beta-amyloid accumulation was characterized with [18F] Florbetapir positron emission tomography scans. CVR was calculated as middle cerebral artery blood flow velocity change from rest to moderate intensity exercise. We found that individuals with elevated beta-amyloid aggregation had a blunted CVR ( n = 25, age 70.1 ± 4.8; 3.3 ± 3.7 cm/s) compared to non-elevated individuals ( n = 45, age 72...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28912896/investigation-of-the-safety-of-focused-ultrasound-induced-blood-brain-barrier-opening-in-a-natural-canine-model-of-aging
#3
Meaghan Anne O'Reilly, Ryan Matthew Jones, Edward Barrett, Anthony Schwab, Elizabeth Head, Kullervo Hynynen
Rationale: Ultrasound-mediated opening of the Blood-Brain Barrier(BBB) has shown exciting potential for the treatment of Alzheimer's disease(AD). Studies in transgenic mouse models have shown that this approach can reduce plaque pathology and improve spatial memory. Before clinical translation can occur the safety of the method needs to be tested in a larger brain that allows lower frequencies be used to treat larger tissue volumes, simulating clinical situations. Here we investigate the safety of opening the BBB in half of the brain in a large aged animal model with naturally occurring amyloid deposits...
2017: Theranostics
https://www.readbyqxmd.com/read/28911689/effect-of-oleuropein-against-chemotherapy-drug-induced-histological-changes-oxidative-stress-and-dna-damages-in-rat-kidney-injury
#4
Fatime Geyikoglu, Murat Emir, Suat Colak, Kubra Koc, Hasan Turkez, Murat Bakir, Mirkhalil Hosseinigouzdagani, Salim Cerig, Osman Nuri Keles, Nihal Simsek Ozek
Cisplatin-based chemotherapy is responsible for a large number of renal failures, and it is still associated with high rates of mortality today. Oleuropein (OLE) presents a plethora of pharmacological beneficial properties. In this study we investigated whether OLE could provide sufficient protection against cisplatin-induced nephrotoxicity. With this aim, Sprague-Dawley rats were divided into eight groups: control; 7 mg/kg/d cisplatin, 50 mg/kg, 100 mg/kg, and 200 mg/kg OLE; and treatment with OLE for 3 days starting at 24 hours following cisplatin injection...
April 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28906150/safety-and-efficacy-of-a-ttr-specific-antisense-oligonucleotide-in-patients-with-transthyretin-amyloid-cardiomyopathy
#5
Merrill D Benson, Noel R Dasgupta, Stacy M Rissing, Jessica Smith, Harvey Feigenbaum
OBJECTIVES: Cardiomyopathy is a major cause of death in both the hereditary form of transthyretin (TTR) amyloidosis and the sporadic late-age-onset transthyretin amyloidosis (ATTR wild-type (ATTRwt)). Clinically disease progression from time of diagnosis to death is usually quoted as 5- to 15-years. In prior studies, significant progression of cardiac parameters in patients with moderate to severe cardiomyopathy has been noted within a 12-month time span. METHODS: The present study was designed to prospectively monitor changes in cardiac parameters, both structural and functional, in patients with ATTR cardiomyopathy while treated with a TTR specific antisense oligonucleotide (ASO; IONIS-TTR℞) designed to lower blood levels of the amyloid fibril precursor protein...
September 14, 2017: Amyloid: the International Journal of Experimental and Clinical Investigation
https://www.readbyqxmd.com/read/28902142/blood-brain-barrier-dysfunction-and-the-pathogenesis-of-alzheimer-s-disease
#6
REVIEW
Yu Yamazaki, Takahisa Kanekiyo
Brain capillary endothelial cells form the blood-brain barrier (BBB), which is covered with basement membranes and is also surrounded by pericytes and astrocyte end-feet in the neurovascular unit. The BBB tightly regulates the molecular exchange between the blood flow and brain parenchyma, thereby regulating the homeostasis of the central nervous system (CNS). Thus, dysfunction of the BBB is likely involved in the pathogenesis of several neurological diseases, including Alzheimer's disease (AD). While amyloid-β (Aβ) deposition and neurofibrillary tangle formation in the brain are central pathological hallmarks in AD, cerebrovascular lesions and BBB alteration have also been shown to frequently coexist...
September 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28900428/c-reactive-protein-binds-to-cholesterol-crystals-and-co-localizes-with-the-terminal-complement-complex-in-human-atherosclerotic-plaques
#7
Katrine Pilely, Stefano Fumagalli, Anne Rosbjerg, Ninette Genster, Mikkel-Ole Skjoedt, Carlo Perego, Angela M R Ferrante, Maria-Grazia De Simoni, Peter Garred
Inflammation is a part of the initial process leading to atherosclerosis and cholesterol crystals (CC), found in atherosclerotic plaques, which are known to induce complement activation. The pentraxins C-reactive protein (CRP), long pentraxin 3 (PTX3), and serum amyloid P component (SAP) are serum proteins associated with increased risk of cardiovascular events and these proteins have been shown to interact with the complement system. Whether the pentraxins binds to CC and mediate downstream complement-dependent inflammatory processes remains unknown...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28895034/whole-body-biodistribution-and-the-influence-of-body-activity-on-brain-kinetic-analysis-of-the-11-c-pib-pet-scan
#8
Go Akamatsu, Tomoyuki Nishio, Kazuhiko Adachi, Yasuhiko Ikari, Michio Senda
Dynamic (11)C-PiB PET imaging with kinetic analysis has been performed for accurate quantification of amyloid binding in patients with Alzheimer's disease (AD). In this study, we measured the whole-body biodistribution of (11)C-PiB in nine subjects. We then evaluated the effect of body activity on quantitative accuracy of brain (11)C-PiB three-dimensional (3D) dynamic PET. Based on clinical biodistribution data, we conducted phantom experiments to estimate the effect of body activity on quantification of the brain 3D dynamic (11)C-PiB PET data and the error introduced by body activity using six different PET camera models...
September 11, 2017: Radiological Physics and Technology
https://www.readbyqxmd.com/read/28890893/proximate-mediators-of-microvascular-dysfunction-at-the-blood-brain-barrier-neuroinflammatory-pathways-to-neurodegeneration
#9
REVIEW
Barry W Festoff, Ravi K Sajja, Luca Cucullo
Current projections are that by 2050 the numbers of people aged 65 and older with Alzheimer's disease (AD) in the US may increase threefold while dementia is projected to double every 20 years reaching ~115 million by 2050. AD is clinically characterized by progressive dementia and neuropathologically by neuronal and synapse loss, accumulation of amyloid plaques, and neurofibrillary tangles (NFTs) in specific brain regions. The preclinical or presymptomatic stage of AD-related brain changes may begin over 20 years before symptoms occur, making development of noninvasive biomarkers essential...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28888720/aged-chimpanzees-exhibit-pathologic-hallmarks-of-alzheimer-s-disease
#10
Melissa K Edler, Chet C Sherwood, Richard S Meindl, William D Hopkins, John J Ely, Joseph M Erwin, Elliott J Mufson, Patrick R Hof, Mary Ann Raghanti
Alzheimer's disease (AD) is a uniquely human brain disorder characterized by the accumulation of amyloid-beta protein (Aβ) into extracellular plaques, neurofibrillary tangles (NFT) made from intracellular, abnormally phosphorylated tau, and selective neuronal loss. We analyzed a large group of aged chimpanzees (n = 20, age 37-62 years) for evidence of Aβ and tau lesions in brain regions affected by AD in humans. Aβ was observed in plaques and blood vessels, and tau lesions were found in the form of pretangles, NFT, and tau-immunoreactive neuritic clusters...
August 1, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28883786/arterial-pulsations-cannot-drive-intramural-periarterial-drainage-significance-for-a%C3%AE-drainage
#11
Alexandra K Diem, Matthew MacGregor Sharp, Maureen Gatherer, Neil W Bressloff, Roxana O Carare, Giles Richardson
Alzheimer's Disease (AD) is the most common form of dementia and to date there is no cure or efficient prophylaxis. The cognitive decline correlates with the accumulation of amyloid-β (Aβ) in the walls of capillaries and arteries. Our group has demonstrated that interstitial fluid and Aβ are eliminated from the brain along the basement membranes of capillaries and arteries, the intramural periarterial drainage (IPAD) pathway. With advancing age and arteriosclerosis, the stiffness of arterial walls, this pathway fails in its function and Aβ accumulates in the walls of arteries...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28882786/exosomal-biomarkers-in-down-syndrome-and-alzheimer-s-disease
#12
REVIEW
Eric D Hamlett, Aurélie Ledreux, Huntington Potter, Heidi J Chial, David Patterson, Joaquin M Espinosa, Brianne M Bettcher, Ann-Charlotte Granholm
Every person with Down syndrome (DS) has the characteristic features of Alzheimer's disease (AD) neuropathology in their brain by the age of forty, and most go on to develop AD dementia. Since people with DS show highly variable levels of baseline function, it is often difficult to identify early signs of dementia in this population. The discovery of blood biomarkers predictive of dementia onset and/or progression in DS is critical for developing effective clinical diagnostics. Our recent studies show that neuron-derived exosomes, which are small extracellular vesicles secreted by most cells in the body, contain elevated levels of amyloid-beta peptides and phosphorylated-Tau that could indicate a preclinical AD phase in people with DS starting in childhood...
September 4, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28874832/antibiotic-induced-perturbations-in-microbial-diversity-during-post-natal-development-alters-amyloid-pathology-in-an-aged-appswe-ps1%C3%AE-e9-murine-model-of-alzheimer-s-disease
#13
Myles R Minter, Reinhard Hinterleitner, Marlies Meisel, Can Zhang, Vanessa Leone, Xiaoqiong Zhang, Paul Oyler-Castrillo, Xulun Zhang, Mark W Musch, Xunuo Shen, Bana Jabri, Eugene B Chang, Rudolph E Tanzi, Sangram S Sisodia
Recent evidence suggests the commensal microbiome regulates host immunity and influences brain function; findings that have ramifications for neurodegenerative diseases. In the context of Alzheimer's disease (AD), we previously reported that perturbations in microbial diversity induced by life-long combinatorial antibiotic (ABX) selection pressure in the APPSWE/PS1ΔE9 mouse model of amyloidosis is commensurate with reductions in amyloid-β (Aβ) plaque pathology and plaque-localised gliosis. Considering microbiota-host interactions, specifically during early post-natal development, are critical for immune- and neuro-development we now examine the impact of microbial community perturbations induced by acute ABX exposure exclusively during this period in APPSWE/PS1ΔE9 mice...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28871412/rage-nf-%C3%AE%C2%BAb-ppar%C3%AE-signaling-is-involved-in-ages-induced-upregulation-of-amyloid-%C3%AE-influx-transport-in-an-in-vitro-bbb-model
#14
Fang Chen, Arijit Ghosh, Mei Hu, Yan Long, Hongbin Sun, Lingyi Kong, Hao Hong, Susu Tang
The receptor for advanced glycation end products (RAGE) at the blood-brain barrier (BBB) is critical for regulation of amyloid-β (Aβ) homeostasis in the diabetic brain. In this study, we used an in vitro BBB model consisting of mouse brain capillary endothelial cells (MBCECs) to investigate whether advanced glycation end products (AGEs) increase Aβ influx transport across the BBB and the underlying mechanisms. We found that AGEs induced Aβ influx transport across the BBB in concentration- and time-dependent manner, accompanied by increased RAGE expression and nuclear factor-kappa B p65 (NF-κB p65), and decreased nuclear peroxisome proliferator-activated receptor γ (PPARγ)...
September 4, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28869476/pazopanib-reduces-phosphorylated-tau-levels-and-alters-astrocytes-in-a-mouse-model-of-tauopathy
#15
Monica Javidnia, Michaeline L Hebron, Yue Xin, Nikolas G Kinney, Charbel E-H Moussa
Hyperphosphorylation and aggregation of tau protein is a critical factor in many neurodegenerative diseases. These diseases are increasing in prevalence, and there are currently no cures. Previous work from our group and others has shown that tyrosine kinase inhibitors (TKIs) can stimulate autophagy, decrease pathological proteins, and improve symptoms in models of neurodegeneration. Here we examined the role of pazopanib in mouse models that express either human mutant P301L tau (TauP301L) or triple mutant amyloid precursor protein (3x-AβPP)...
September 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28865214/serum-amyloid-a-protein-saa-haptoglobin-hp-and-selected-hematological-and-biochemical-parameters-in-wild-mares-before-and-after-parturition
#16
L Krakowski, P Bartoszek, I Krakowska, P Olcha, T Piech, A Stachurska, P Brodzki
The aim of the study was to evaluate physiological changes in hematological and biochemical parameters in mares in perinatal period. Blood samples were collected from 24 pregnant Polish Konik breed mares which were divided into two groups. The first group (Group - I, n=12) comprised mares living in the wild, in the reserve. The second group (Group - II, n=12) consisted of mares kept in stables. The blood was collected 2 weeks prior to the parturition, then 24 hours after the delivery, and then at the 7th and 21st day after foaling...
March 1, 2017: Polish Journal of Veterinary Sciences
https://www.readbyqxmd.com/read/28861757/histamine-h3-inverse-agonist-bf-2649-or-antagonist-with-partial-h4-agonist-activity-clobenpropit-reduces-amyloid-beta-peptide-induced-brain-pathology-in-alzheimer-s-disease
#17
Ranjana Patnaik, Aruna Sharma, Stephen D Skaper, Dafin F Muresanu, José Vicente Lafuente, Rudy J Castellani, Ala Nozari, Hari S Sharma
Alzheimer's disease (AD) is one of the leading causes for disability and death affecting millions of people worldwide. Thus, novel therapeutic strategies are needed to reduce brain pathology associated with AD. In view of increasing awareness regarding involvement of histaminergic pathways in AD, we explored the role of one H3 receptor inverse agonist BF 2649 and one selective H3 receptor antagonist with partial H4 agonist activity in amyloid beta peptide (AβP) infusion-induced brain pathology in a rat model...
August 31, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28860067/a-novel-role-for-osteopontin-in-macrophage-mediated-amyloid-%C3%AE-clearance-in-alzheimer-s-models
#18
Altan Rentsendorj, Julia Sheyn, Dieu-Trang Fuchs, David Daley, Brenda C Salumbides, Hannah E Schubloom, Nadav J Hart, Songlin Li, Eric Y Hayden, David B Teplow, Keith L Black, Yosef Koronyo, Maya Koronyo-Hamaoui
Osteopontin (OPN), a matricellular immunomodulatory cytokine highly expressed by bone marrow (BM)-derived myelomonocytes, regulates immune cell migration, communication, and response to brain injury. Enhanced cerebral recruitment of monocytes and macrophages by immunomodulation using glatiramer acetate (GA) or by peripheral blood enrichment with BM-derived CD115(+) monocytes (Mo(BM)) substantially curbs amyloid β-protein (Aβ) neuropathology and preserves cognitive function in murine models of Alzheimer's disease (ADtg mice)...
August 28, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28860054/detection-of-contactin-2-in-cerebrospinal-fluid-csf-of-patients-with-alzheimer-s-disease-using-fluorescence-correlation-spectroscopy-fcs
#19
Madhurima Chatterjee, Bernd Nöding, Eline A J Willemse, Marleen J A Koel-Simmelink, Wiesje M van der Flier, Detlev Schild, Charlotte E Teunissen
OBJECTIVES: Alzheimer's disease (AD) is the most common cause of dementia in the world. As many AD biomarkers occur at rather low abundances in CSF or blood, techniques of very high sensitivity and accuracy are important as diagnostic tools in the clinic. Here, we aimed to provide proof of concept of the use of a single molecule detection technique, Fluorescence Correlation Spectroscopy (FCS) for detection of novel candidate biomarkers for AD. DESIGN AND METHODS: FCS detects the diffusion times of the antigen-antibody complexes in highly diluted sample solutions, thus eliminating the need of large sample volumes and allows estimating the concentration of the target antigen...
August 28, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28859225/widespread-brain-distribution-and-activity-following-anti-bace1-intracerebroventricular-infusion-in-nonhuman-primates
#20
Daniela Bumbaca Yadav, Janice A Maloney, Kristin R Wildsmith, Reina N Fuji, William J Meilandt, Hilda Solanoy, Yanmei Lu, Kun Peng, Blair Wilson, Pamela Chan, Kapil Gadkar, Andrew Kosky, Marisa Goo, Ann Daugherty, Jessica A Couch, Thomas Keene, Karen Hayes, Lisa Jungbauer Nikolas, Deanna Lane, Robert Switzer, Eric Adams, Ryan J Watts, Kimberly Scearce-Levie, Saileta Prabhu, Lisa Shafer, Deepak R Thakker, Keith Hildebrand, Jasvinder K Atwal
BACKGROUND AND PURPOSE: The potential for therapeutic antibody treatment of neurological diseases is limited by poor penetration across the blood-brain barrier. Intracerebroventricular (i.c.v.) delivery is a promising route to the brain, however it is unclear how efficiently i.c.v - delivered antibodies penetrate the cerebrospinal fluid (CSF)-brain barrier and distribute throughout the brain parenchyma. EXPERIMENTAL APPROACH: We evaluated the pharmacokinetics and pharmacodynamics of an inhibitory monoclonal antibody against β-site amyloid precursor protein cleaving enzyme 1 (anti-BACE1) following continuous infusion into the left lateral ventricle of healthy adult cynomolgus monkeys...
August 31, 2017: British Journal of Pharmacology
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