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https://www.readbyqxmd.com/read/29335442/nanostructural-differentiation-and-toxicity-of-amyloid-%C3%AE-25-35-aggregates-ensue-from-distinct-secondary-conformation
#1
Yongxiu Song, Ping Li, Lei Liu, Christian Bortolini, Mingdong Dong
Amyloid nanostructures are originated from protein misfolding and aberrant aggregation, which is associated with the pathogenesis of many types of degenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease. The secondary conformation of peptides is of a fundamental importance for aggregation and toxicity of amyloid peptides. In this work, Aβ25-35, a fragment of amyloid β(1-42) (Aβ42), was selected to investigate the correlation between secondary structures and toxicity of amyloid fibrils...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29326853/purtscher-like-retinopathy-associated-with-atypical-hemolytic-uremic-syndrome
#2
Melih Ustaoğlu, Feyza Önder, Nilgün Solmaz, Savaş Öztürk, Mesut Ayer
A 25-year-old woman presented with acute bilateral blurred vision and history of headache, dizziness, and syncope for three days. Her visual acuity was 20/60 in both eyes. Fundoscopy revealed multiple bilateral peripapillary yellow-white patches like cotton wool spots, intraretinal hemorrhages and macular edema. The patient was diagnosed with Purtscher-like retinopathy based on the retinal findings and lack of trauma history. She was urgently admitted to the nephrology clinic due to thrombotic microangiopathy findings (hemoglobinemia, thrombocytopenia, and acute renal failure)...
December 2017: Turkish Journal of Ophthalmology
https://www.readbyqxmd.com/read/29322109/influence-of-hydrodynamic-features-in-the-transport-and-fate-of-hazard-contaminants-within-touristic-ports-case-study-torre-a-mare-italy
#3
Matilda Mali, Daniela Malcangio, Maria Michela Dell' Anna, Leonardo Damiani, Piero Mastrorilli
The environmental quality of Torre a Mare port (Italy) was assessed evaluating on one side, the chemical concentration of nine metals and metalloids within bottom sediments and on the other one, by exploring the impact of hydrodynamic conditions in contaminant's transport within the most polluted basins. The investigated port was selected as case study because it resulted much more polluted than it was expected based on the touristic port activities and related stressors loading on it. In order to determine the origin and fate of contaminants in the port basin, 2D numerical simulations were carried out by MIKE21 software...
January 2018: Heliyon
https://www.readbyqxmd.com/read/29320887/transducing-airway-basal-cells-with-a-helper-dependent-adenoviral-vector-for-lung-gene-therapy
#4
Huibi Cao, Hong Ouyang, Hartmut Grasemann, Claire Bartlett, Kai Du, Rongqi Duan, Fushan Shi, Marvin Estrada, Kyle Seigel, Allan Coates, Herman Yeger, Christine Bear, Tanja Gonska, Theo Moraes, Jim Hu
A major challenge in developing gene-based therapies for airway diseases such as cystic fibrosis (CF) is sustaining therapeutic levels of transgene expression over time. This is largely due to airway epithelial cell turnover and the host immunogenicity to gene delivery vectors. Modern gene editing tools and delivery vehicles hold great potential for overcoming the challenge. There is currently not much known about how to deliver genes into airway stem cells, of which basal cells are the major type in human airways...
January 10, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29317338/astrocytes-as-targets-for-drug-discovery
#5
REVIEW
Kirill Gorshkov, Francis Aguisanda, Natasha Thorne, Wei Zheng
Recent studies have illuminated the crucial role of astrocytes in maintaining proper neuronal health and function. Abnormalities in astrocytic functions have now been implicated in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Historically, drug development programs for neurodegenerative diseases generally target only neurons, overlooking the contributions of astrocytes. Therefore, targeting both disease neurons and astrocytes offers a new approach for drug development for the treatment of neurological diseases...
January 6, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29305855/microglia-derived-extracellular-vesicles-in-alzheimer-s-disease-a-double-edged-sword
#6
REVIEW
Teresa Trotta, Maria Antonietta Panaro, Antonia Cianciulli, Giorgio Mori, Adriana Di Benedetto, Chiara Porro
Extracellular vesicles (EVs), based on their origin or size, can be classified as apoptotic bodies, microvesicles (MVs)/microparticles (MPs), and exosomes. EVs are one of the new emerging modes of communication between cells that are providing new insights into the pathophysiology of several diseases. EVs released from activated or apoptotic cells contain specific proteins (signaling molecules, receptors, integrins, cytokines), bioactive lipids, nucleic acids (mRNA, miRNA, small non coding RNAs, DNA) from their progenitor cells...
January 3, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29302618/time-restricted-feeding-improves-circadian-dysfunction-as-well-as-motor-symptoms-in-the-q175-mouse-model-of-huntington-s-disease
#7
Huei-Bin Wang, Dawn H Loh, Daniel S Whittaker, Tamara Cutler, David Howland, Christopher S Colwell
Huntington's disease (HD) patients suffer from a progressive neurodegeneration that results in cognitive, psychiatric, cardiovascular, and motor dysfunction. Disturbances in sleep/wake cycles are common among HD patients with reports of delayed sleep onset, frequent bedtime awakenings, and fatigue during the day. The heterozygous Q175 mouse model of HD has been shown to phenocopy many HD core symptoms including circadian dysfunctions. Because circadian dysfunction manifests early in the disease in both patients and mouse models, we sought to determine if early intervention that improve circadian rhythmicity can benefit HD and delay disease progression...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29298483/a-metal-protein-attenuating-compound-for-pet-neuroimaging-synthesis-and-preclinical-evaluation-of-11c-pbt2
#8
Hema S Krishnan, Vadim Bernard-Gauthier, Michael Stephen Placzek, Kenneth Dahl, Vidya Narayanaswami, Elijahu Livni, Zhen Chen, Jing Yang, Thomas Lee Collier, Chongzhao Ran, Jacob M Hooker, Steven H Liang, Neil Vasdev
Dyshomeostasis or abnormal accumulation of metal ions such as copper, zinc and iron have been linked to the pathogenesis of multiple neurodegenerative disorders including Alzheimer's disease (AD) and Huntington's disease (HD). 5,7-Dichloro-2-((dimethylamino)methyl)quinolin-8-ol, PBT2, is a second generation metal protein-attenuating compound that has recently advanced in Phase II clinical trials for the treatment of AD and HD based on promising preclinical efficacy data. Herein, we report the first radiosynthesis and preclinical positron emission tomography (PET) neuroimaging evaluation of [11C]PBT2 in rodents and nonhuman primates...
January 3, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29296170/end-stage-renal-disease-is-associated-with-development-of-dementia
#9
Peir-Haur Hung, Chih-Ching Yeh, Chih-Yen Hsiao, Pi-Shan Sung, Chih-Hsin Muo, Fung-Chang Sung, Kuan-Yu Hung, Kuen-Jer Tsai
There is controversy regarding the extent of risk for dementia in patients with end stage renal disease (ESRD) who are undergoing hemodialysis (HD) or peritoneal dialysis (PD). We examined data from Taiwan's Longitudinal Health Insurance Database, and used Cox proportional hazard regression analysis to compare the development of dementia in 72,934 HD and PD patients with 72,934 matched controls from January 1, 1999 to December 31, 2010. The results indicate an increased risk for dementia overall in HD patients (adjusted hazard ratio [aHR] = 1...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29246205/the-autism-tics-adhd-and-other-comorbidities-inventory-a-tac-previous-and-predictive-validity
#10
Caroline Mårland, Paul Lichtenstein, Alessio Degl'Innocenti, Tomas Larson, Maria Råstam, Henrik Anckarsäter, Christopher Gillberg, Thomas Nilsson, Sebastian Lundström
BACKGROUND: Reliable and easy to administer screening instruments focusing on neurodevelopmental disorders and associated conditions are scarce. The Autism-Tics, AD/HD and other Comorbidities inventory (A-TAC) has previously been validated and reporting good- excellent validity for several disorders. This article aims to expand these findings by including more conditions in a substantially larger sample augmented with the Swedish National Patient Register (NPR). METHODS: Since 2004 parents of all 9-year-old Swedish twins have been invited to participate in a telephone interview in the Child and Adolescent Twin Study in Sweden, CATSS...
December 16, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/29228015/development-of-an-iron-selective-antioxidant-probe-with-protective-effects-on-neuronal-function
#11
Olimpo García-Beltrán, Natalia P Mena, Pabla Aguirre, Germán Barriga-González, Antonio Galdámez, Edgar Nagles, Tatiana Adasme, Cecilia Hidalgo, Marco T Núñez
Iron accumulation, oxidative stress and calcium signaling dysregulation are common pathognomonic signs of several neurodegenerative diseases, including Parkinson´s and Alzheimer's diseases, Friedreich ataxia and Huntington's disease. Given their therapeutic potential, the identification of multifunctional compounds that suppress these damaging features is highly desirable. Here, we report the synthesis and characterization of N-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)-2-(7-hydroxy-2-oxo-2H-chromen-4-yl)acetamide, named CT51, which exhibited potent free radical neutralizing activity both in vitro and in cells...
2017: PloS One
https://www.readbyqxmd.com/read/29224028/atp-binding-cassette-subfamily-a-member-2-abca2-expression-and-methylation-are-associated-with-alzheimer-s-disease
#12
Wanhua Hu, Xiaodong Lin, Huihe Zhang, Na Zhao
BACKGROUND ABCA2 has been genetically linked to Alzheimer's disease (AD) risk, but its mRNA expression and epigenetics in AD have not been investigated. MATERIAL AND METHODS To explore the diagnosis value of ABCA2 mRNA expression in AD, 2 datasets GES15222 and GSE33000 containing expression profile of brain cortex tissues and 2 datasets GSE63063 (Cohort 1) and GSE63063 (Cohort 2) containing expression profile of blood were downloaded from the NCBI GEO database and analyzed by receiver operating characteristic curve (ROC) analyses and logistic regression...
December 10, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29218425/ionized-and-total-serum-magnesium-in-hemodialysis-predictors-and-variability-a-longitudinal-cross-sectional-study
#13
Rosaria Del Giorno, Hilary Riva, Gaetano Donato, Luca Gabutti
BACKGROUND: Ionized Magnesium (ion-Mg) represents the active biological fraction of the serum magnesium content. The assessment of total serum Mg (tot-Mg) might not accurately identify patients with hypo-or hyper-magnesaemie. In hemodialysis, serum tot-Mg levels in the upper part of the distribution, have been associated with reduced mortality and fewer vascular calcifications; thus, resulting in the tendency to increase the Mg concentration in the dialysate, traditionally set at 0.5 mmol/L...
December 7, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29213063/efficacy-and-safety-of-hd-mtx-based-systemic-chemotherapy-regimens-retrospective-study-of-induction-therapy-for-primary-central-nervous-system-lymphoma-in-chinese
#14
Xiao Han, Yali Ji, Mingqi Ouyang, Tienan Zhu, Daobin Zhou
We performed a retrospective study of 49 patients with newly diagnosed primary central nervous system lymphoma (PCNSL), to compare the efficacy and safety of different high-dose methotrexate (HD-MTX) based systemic chemotherapy regimens as induction therapy. 25 patients received AB ± R alternative regimen (consist methotrexate, ifosfamide, vindesine, dexamethasone, carmustine and teniposide), while others received HD-MTX ± R regimen. The complete response rate and overall response rate of AB ± R group and HD-MTX ± R group were 36...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29204109/intracellular-cholesterol-trafficking-and-impact-in-neurodegeneration
#15
REVIEW
Fabian Arenas, Carmen Garcia-Ruiz, Jose C Fernandez-Checa
Cholesterol is a critical component of membrane bilayers where it plays key structural and functional roles by regulating the activity of diverse signaling platforms and pathways. Particularly enriched in brain, cholesterol homeostasis in this organ is singular with respect to other tissues and exhibits a heterogeneous regulation in distinct brain cell populations. Due to the key role of cholesterol in brain physiology and function, alterations in cholesterol homeostasis and levels have been linked to brain diseases and neurodegeneration...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29203337/shati-nat8l-knockout-mice-show-behavioral-deficits-ameliorated-by-atomoxetine-and-methylphenidate
#16
Kazuya Toriumi, Junko Tanaka, Takayoshi Mamiya, Tursun Alkam, Hyoung-Chun Kim, Atsumi Nitta, Toshitaka Nabeshima
We previously identified a novel molecule, SHATI/NAT8L, as having an inhibitory effect on methamphetamine dependence. We generated Shati/Nat8l knockout (KO) mice and found that they showed neurochemical changes and behavioral abnormalities related to attention deficit/hyperactivity disorder (AD/HD). In this study, we assessed validities of the Shati/Nat8l KO mice as a new animal model for AD/HD through a behavioral pharmacology approach. We conducted a locomotor activity test in a novel environment, a cliff avoidance test, and an object-based attention assay using Shati/Nat8l KO mice at the ages of 4 and 8 weeks...
December 1, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29177651/measurement-of-chaperone-mediated-effects-on-polyglutamine-protein-aggregation-by-the-filter-trap-assay
#17
Maria A W H van Waarde-Verhagen, Harm H Kampinga
The formation of aggregates by polyglutamine-containing (polyQ) proteins in neurons is a key to the pathogenesis of several progressive neurodegenerative diseases such as Huntington's disease (HD) spinocerebellar ataxias (SCAs), and spinal and bulbar muscular atrophy (SBMA). In order to study whether the members of the heat shock protein (HSP) families, by virtue of their molecular chaperone activity, can inhibit the formation of polyQ aggregates, we developed a cell culture model expressing the GFP tagged fragment of exon1 of the huntingtin gene with an expanded polyQ chain and tetracycline inducible chaperones...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29175000/cyclic-nucleotide-signaling-changes-associated-with-normal-aging-and-age-related-diseases-of-the-brain
#18
REVIEW
Michy P Kelly
Deficits in brain function that are associated with aging and age-related diseases benefit very little from currently available therapies, suggesting a better understanding of the underlying molecular mechanisms is needed to develop improved drugs. Here, we review the literature to test the hypothesis that a break down in cyclic nucleotide signaling at the level of synthesis, execution, and/or degradation may contribute to these deficits. A number of findings have been reported in both the human and animal model literature that point to brain region-specific changes in Galphas (a...
January 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29171099/regional-citrate-anticoagulation-for-intermittent-hemodialysis-in-dogs
#19
T Francey, A Schweighauser
BACKGROUND: The traditional systemic heparinization used for anticoagulation in extracorporeal therapies may cause fatal complications in animals at risk of bleeding. HYPOTHESIS/OBJECTIVES: To develop and validate a protocol of regional citrate anticoagulation (RCA) for intermittent hemodialysis in dogs. ANIMALS: A total of 172 dogs treated with hemodialysis for acute kidney injury. METHODS: In vitro titration was performed, adding trisodium citrate and calcium chloride to heparinized canine blood...
November 24, 2017: Journal of Veterinary Internal Medicine
https://www.readbyqxmd.com/read/29166634/sodium-prescription-in-the-prevention-of-intradialytic-hypotension-new-insights-into-an-old-concept
#20
Gabriele Donati, Mauro Ursino, Alessandra Spazzoli, Nicolò Natali, Roberto Schillaci, Diletta Conte, Andrea Angeletti, Anna Laura Croci Chiocchini, Irene Capelli, Olga Baraldi, Gaetano La Manna
BACKGROUND: Sodium prescription in patients with intradialytic hypotension remains a challenge for the attending nephrologist, as it increases dialysate conductivity in hypotension-prone patients, thereby adding to dietary sodium levels. METHODS: New sodium prescription strategies are now available, including the use of a mathematical model to compute the sodium mass to be removed during dialysis as a physiological controller. RESULTS: This review describes the sodium load of patients with end-stage renal disease on chronic hemodialysis (HD) and discusses 2 strategies to remove excess sodium in patients prone to intradialytic hypotension, namely, Profiled HD and the hemodiafiltration Aequilibrium System...
November 23, 2017: Blood Purification
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