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https://www.readbyqxmd.com/read/29172520/copper-i-chelators-for-alzheimer-s-disease
#1
Stanley Opare, Arvi Rauk
A component of the neurotoxicity of the beta amyloid peptide (Aβ) of Alzheimer's disease is its ability to generate superoxide, hydrogen peroxide and hydroxyl radicals by the reaction of its reduced copper complex, Aβ/Cu+ has with molecular oxygen. The objective of the present work was to devise compounds, L, that could remove Cu+ from Aβ/Cu+, with the property that L/Cu+ itself would not be capable of reducing O2 or hydrogen peroxide. We show by density functional calculations that several pincer-type compounds with two imidazole rings and a sulphur or nitrogen, have the desired combination of Cu+ binding affinity and Cu2+ reduction potential...
November 27, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29168380/quantitative-study-of-oligomerization-of-yeast-prion-sup35nm-proteins
#2
Yanjing Wang, Chi Wu
The fibrillation of misfolded neurodegenerative diseases related proteins has been extensively studied in the last few decades, but the initial oligomerization has been rarely touched even though some recent evidences indicated that small protein oligomers are more neurotoxic than long protein fibers. It is rather difficult to study the initial oligomerization (nucleation) because most of experimental methods, such as β-sheet related fluorescence assay and X-ray diffraction, are helpless in detecting small structure-less protein oligomers...
November 23, 2017: Biochemistry
https://www.readbyqxmd.com/read/29151132/safety-of-intrathecal-route-focus-to-methylprednisolone-acetate-depo-medrol-use
#3
REVIEW
Joël Schlatter, David Nguyen, Michèle Zamy, Sofiane Kabiche, Jean-Eudes Fontan, Salvatore Cisternino
PURPOSE: Complications of the intrathecal route may cause potential toxicity related to the medical device and properties of the administered drug and/or excipient. A description of clinical and histological effects of polyethylene glycol and miripirium after Depo-Medrol injection, and the adverse reactions of particulate methylprednisolone acetate was conducted. The safety of the intrathecal route with excipients, label and off-label drugs is discussed. METHODS: A bibliographic search in Medline, Google, and Cochrane database from 1940 to June 2016 was performed...
November 18, 2017: European Spine Journal
https://www.readbyqxmd.com/read/29145874/peripheral-immune-tolerance-alleviates-the-intracranial-lipopolysaccharide-injection-induced-neuroinflammation-and-protects-the-dopaminergic-neurons-from-neuroinflammation-related-neurotoxicity
#4
Yang Liu, Xin Xie, Li-Ping Xia, Hong Lv, Fan Lou, Yan Ren, Zhi-Yi He, Xiao-Guang Luo
BACKGROUND: Neuroinflammation plays a critical role in the onset and development of neurodegeneration disorders such as Parkinson's disease. The immune activities of the central nervous system are profoundly affected by peripheral immune activities. Immune tolerance refers to the unresponsiveness of the immune system to continuous or repeated stimulation to avoid excessive inflammation and unnecessary by-stander injury in the face of continuous antigen threat. It has been proved that the immune tolerance could suppress the development of various peripheral inflammation-related diseases...
November 16, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29137682/cefepime-induced-neurotoxicity-a-systematic-review
#5
Lauren E Payne, David J Gagnon, Richard R Riker, David B Seder, Elizabeth K Glisic, Jane G Morris, Gilles L Fraser
BACKGROUND: Cefepime is a widely used antibiotic with neurotoxicity attributed to its ability to cross the blood-brain barrier and exhibit concentration-dependent ϒ-aminobutyric acid (GABA) antagonism. Neurotoxic symptoms include depressed consciousness, encephalopathy, aphasia, myoclonus, seizures, and coma. Data suggest that up to 15% of ICU patients treated with cefepime may experience these adverse effects. Risk factors include renal dysfunction, excessive dosing, preexisting brain injury, and elevated serum cefepime concentrations...
November 14, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/29137186/dopaminergic-dysfunction-in-mammalian-dopamine-neurons-induced-by-simazine-neurotoxicity
#6
Xueting Li, Jia Yu, Jianan Li, Yanping Wu, Baixiang Li
Many studies have shown that the pollutant simazine (6-chloro-N,N'-diethyl-1,3,5-triazine-2,4-diamine), which has been overused, inhibits the proliferation of mammalian dopaminergic cells, and affects the developmental differentiation of mammalian dopaminergic neurons. However, few studies have shown the effects of simazine on dopaminergic metabolism in these cells. Therefore, we aim to examine the metabolic effects of simazine exposure in mouse dopaminergic progenitor neurons (MN9D) at different exposure times...
November 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29134560/neurochemical-and-neurotoxic-effects-of-mdma-ecstasy-and-caffeine-after-chronic-combined-administration-in-mice
#7
Anna Maria Górska, Katarzyna Kamińska, Agnieszka Wawrzczak-Bargieła, Giulia Costa, Micaela Morelli, Ryszard Przewłocki, Grzegorz Kreiner, Krystyna Gołembiowska
MDMA (3,4-methylenedioxymethamphetamine) is a psychostimulant popular as a recreational drug because of its effect on mood and social interactions. MDMA acts at dopamine (DA) transporter (DAT) and serotonin (5-HT) transporter (SERT) and is known to induce damage of dopamine and serotonin neurons. MDMA is often ingested with caffeine. Caffeine as a non-selective adenosine A1/A2A receptor antagonist affects dopaminergic and serotonergic transmissions. The aim of the present study was to determine the changes in DA and 5-HT release in the mouse striatum induced by MDMA and caffeine after their chronic administration...
November 13, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29131611/synthesis-and-in-vitro-evaluation-of-monodisperse-amino-functional-polyester-dendrimers-with-rapid-degradability-and-antibacterial-properties
#8
Patrik Stenström, Erik Hjorth, Yuning Zhang, Oliver C J Andrén, Simon Guette-Marquet, Marianne Schultzberg, Michael Malkoch
Amine functional polymers, especially cationically charged, are interesting biomacromolecules for several reasons, including easy cell membrane entrance, their ability to escape endosomes through the proton sponge effect, spontaneous complexation and delivery of drugs and siRNA, and simple functionalization in aqueous solutions. Dendrimers, a subclass of precision polymers, are monodisperse and exhibit a large and exact number of peripheral end groups in relation to their size and have shown promise in drug delivery, biomedical imaging and as antiviral agents...
November 22, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29127491/pink1-attenuates-propofol-induced-apoptosis-and-oxidative-stress-in-developing-neurons
#9
Chao Liang, Fang Du, Jing Cang, Zhanggang Xue
BACKGROUND: The underlying mechanisms of propofol-induced neurotoxicity in developing neurons are still not completely understood. We examined the role of PTEN-induced kinase 1 (Pink1), an antioxidant protein, in propofol-induced apoptosis in developing neurons. MATERIALS AND METHODS: Primary hippocampal neurons isolated from neonatal Sprague-Dawley rats were exposed to propofol 20 μM for 2, 4, 6 and 12 h. Subsequently, neurons underwent overexpression and knockdown of Pink1, followed by propofol exposure (20 μM, 6 h)...
November 10, 2017: Journal of Anesthesia
https://www.readbyqxmd.com/read/29123854/local-anesthetic-toxicity-acute-and-chronic-management
#10
REVIEW
Kenichi Sekimoto, Masaru Tobe, Shigeru Saito
Local anesthetics are commonly used medicines in clinical settings. They are used for pain management during minor interventional treatments, and for postoperative care after major surgeries. Cocaine is the well-known origin of local anesthetics, and the drug and related derivatives have long history of clinical usage for more than several centuries. Although illegal use of cocaine and its abuse are social problem in some countries, other local anesthetics are safely and effectively used in clinics and hospitals all over the world...
April 2017: Acute Medicine & Surgery
https://www.readbyqxmd.com/read/29116375/uncoupling-n-acetylaspartate-from-brain-pathology-implications-for-canavan-disease-gene-therapy
#11
Georg von Jonquieres, Ziggy H T Spencer, Benjamin D Rowlands, Claudia B Klugmann, Andre Bongers, Anne E Harasta, Kristina E Parley, Jennie Cederholm, Orla Teahan, Russell Pickford, Fabien Delerue, Lars M Ittner, Dominik Fröhlich, Catriona A McLean, Anthony S Don, Miriam Schneider, Gary D Housley, Caroline D Rae, Matthias Klugmann
N-Acetylaspartate (NAA) is the second most abundant organic metabolite in the brain, but its physiological significance remains enigmatic. Toxic NAA accumulation appears to be the key factor for neurological decline in Canavan disease-a fatal neurometabolic disorder caused by deficiency in the NAA-degrading enzyme aspartoacylase. To date clinical outcome of gene replacement therapy for this spongiform leukodystrophy has not met expectations. To identify the target tissue and cells for maximum anticipated treatment benefit, we employed comprehensive phenotyping of novel mouse models to assess cell type-specific consequences of NAA depletion or elevation...
November 7, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/29100263/antioxidant-and-neuroprotective-effects-of-km-34-a-novel-synthetic-catechol-against-oxidative-stress-induced-neurotoxicity
#12
Yanier Nuñez-Figueredo, Jeney Ramirez-Sanchez, Yeniceis Alcantara Issac, Estael Ochoa-Rodriguez, Yamila Verdecia-Reyes, Rene Delgado-Hernandez, Diogo O Souza, Gilberto L Pardo Andreu
Free radicals are important mediators in a number of neurodegenerative diseases and molecules capable of scavenging reactive oxygen species (ROS) may be a feasible strategy for protecting neuronal cells. In this sense, polyphenols have been studied for their antioxidant effects, KM-34 (5-(3, 4-dydroxyl-benzylidene)-2, 2-dimethyl-1, 3-dioxane-4, 6-Dione) is a novel synthetic catechol with potential neuroprotective and antioxidant properties. We have assessed the antioxidant (as scavenging and iron-chelating compound) and neuroprotectant in vitro (in PC12 cell injury induced by H2O2, glutamate or FeSO4/AA) of KM-34...
November 3, 2017: Drug Research
https://www.readbyqxmd.com/read/29097283/biomolecular-engineering-of-biocatalysts-hydrolyzing-neurotoxic-organophosphates
#13
Ilya V Lyagin, Elena N Efremenko
Novel methods of molecular modeling help solving urgent problems in drug design, directed evolution of biocatalysts and biosensors, and a lot of other research fields. Implementation of such methods to organophosphorus hydrolase being perfect research object that hydrolyzes dangerous neurotoxic organophosphates could intensify development of antidote and protective preparations to treat poisoning. Structures of enzyme-polyelectrolyte complexes (EPCs) based on hexahistidine-tagged organophosphorus hydrolase (His6-OPH) with different biopolymers (various modifications of polyglutamic and polyaspartic acid, as well as hydroxyethyl starch and succinylated gelatin) were simulated at different pH using molecular docking...
October 30, 2017: Biochimie
https://www.readbyqxmd.com/read/29092802/the-effects-of-mesna-on-the-facial-nerve-an-experimental-animal-study
#14
Deniz Baklacı, Rauf Oğuzhan Kum, Sezer Kulaçoğlu, Yavuz Fuat Yılmaz, Müge Özcan
OBJECTIVE: MESNA (Sodium-2-mercaptoethanesulfonate) is a mucolytic substance that is used for chemically assisted tissue dissection in various surgical operations. The aim of this study was to address the issue of possible neurotoxicity from topical administration of MESNA solution on the facial nerve. We used different concentrations of MESNA solution and evaluated their effects on facial nerve by histopathological and functional analysis. MATERIALS AND METHODS: These groups were the saline administered group (control) (3 rats, 6 facial nerves), the 25% MESNA solution group (3 rats, 6 facial nerves), and the 100% MESNA solution group (3 rats, 6 facial nerves)...
November 2, 2017: Journal of International Advanced Otology
https://www.readbyqxmd.com/read/29092635/hydrogen-sulfide-ameliorates-zinc-induced-cell-death-in-neuroblastoma-sh-sy5y-cells
#15
Megumi Shimoji, Hirokazu Hara, Tetsuro Kamiya, Kensuke Okuda, Tetsuo Adachi
Previous reports have demonstrated that excess zinc (Zn(2+)) released from nerve terminals following cerebral ischemia causes brain injury. Therefore, disturbance of Zn(2+) homeostasis in the brain is thought to be closely linked to neurotoxicity. Recently, hydrogen sulfide (H2S), a gaseous mediator, has been reported to ameliorate ischemic brain injury. However, its mechanism is not fully understood. In this study, we examined whether sodium hydrogen sulfide (NaHS), an H2S donor, protects against Zn(2+) cytotoxicity using human neuroblastoma SH-SY5Y cells...
November 1, 2017: Free Radical Research
https://www.readbyqxmd.com/read/29071893/-influence-of-electroacupuncture-intervention-on-glutamic-acid-and-ca-2-contents-and-expression-of-nmda-receptor-protein-in-hippocampus-in-vascular-dementia-rats
#16
Qian Zhang, Chuang Zhang, Jia-Yin Zhang, Hui-Zhen Zhang, Xiao-Feng Li, Hong-Ling Xiao, Yan-Hui Sun, Hai-Jiao Xing, Xiao-Kang Xu, Yu-Lei Liang, Xin Zhang, Xiao-Qi Zhang, Ai-Ying Li
OBJECTIVE: To observe the influence of electroacupuncture (EA) intervention on hippocampal glutamate (Glu) and Ca(2+) contents, and expression of Glu-N-methyl-D-aspartic acid receptor(NMDAR) and the learning-memory ability in vascular dementia (VD) rats, so as to reveal its mechanisms underlying improvement of VD. METHODS: SD rats were rando-mized into sham operation (sham) group (n=9), model group (n=11) and EA groups (n=10). The VD model was established by repeated bilateral common carotid arteries occlusion and reperfusion plus intraperitoneal injection of sodium nitroprusside...
December 25, 2016: Zhen Ci Yan Jiu, Acupuncture Research
https://www.readbyqxmd.com/read/29059579/metabolic-solutions-to-the-biosynthesis-of-some-diaminomonocarboxylic-acids-in-nature-formation-in-cyanobacteria-of-the-neurotoxins-3-n-methyl-2-3-diaminopropanoic-acid-bmaa-and-2-4-diaminobutanoic-acid-2-4-dab
#17
REVIEW
Peter B Nunn, Geoffrey A Codd
The non-encoded diaminomonocarboxylic acids, 3-N-methyl-2,3-diaminopropanoic acid (syn: α-amino-β-methylaminopropionic acid, MeDAP; β-N-methylaminoalanine, BMAA) and 2,4-diaminobutanoic acid (2,4-DAB), are distributed widely in cyanobacterial species in free and bound forms. Both amino acids are neurotoxic in whole animal and cell-based bioassays. The biosynthetic pathway to 2,4-DAB is well documented in bacteria and in one higher plant species, but has not been confirmed in cyanobacteria. The biosynthetic pathway to BMAA is unknown...
October 20, 2017: Phytochemistry
https://www.readbyqxmd.com/read/29029323/lncrnal20992-regulates-apoptotic-proteins-to-promote-lead-induced-neuronal-apoptosis
#18
Aruo Nan, Yangyang Jia, Xin Li, Meiling Liu, Nan Zhang, Lijian Chen, Ti Yang, Yiqin Xu, Xin Dai, Ying Cheng, Zhenzhong Liu, Yihui Ling, Yiguo Jiang
Lead is a heavy metal pollutant that is widely present in the environment and can seriously harm human health, especially the nervous system. Long noncoding RNAs (lncRNAs) play important roles in many physiological and pathological processes; however, there remains a lack of in-depth studies on the molecular mechanisms associated with lead neurotoxicity. Here, our results showed that lead exposure inhibited cell proliferation and promoted cell apoptosis. We observed that lncRNAL20992 was significantly upregulated in a lead-induced neuronal-injury cell model according to quantitative reverse transcription polymerase chain reaction...
September 25, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28993949/poly-n-methylated-a%C3%AE-peptide-c-terminal-fragments-meptides-reverse-the-deleterious-effects-of-amyloid-%C3%AE-in-rats
#19
Siya G Sibiya, Musa V Mbandla, Thavi Govender, Adeola Shobo, William M U Daniels
Alzheimer's disease (AD) is characterized by extracellular deposition of amyloid-β (Aβ) plaques. These protein deposits impair synaptic plasticity thereby producing a progressive decline in cognitive function. Current therapies are merely palliative and only slow cognitive decline. Poly-N-methylated Aβ-Peptide C-Terminal Fragments (MEPTIDES) were recently shown to reduce Aβ toxicity in vitro and in Drosophila melanogaster, however whether these novel compounds are effective in inhibiting Aβ-induced toxicity in the mammalian brain remains unclear...
October 9, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28958600/methylmercury-promotes-prostacyclin-release-from-cultured-human-brain-microvascular-endothelial-cells-via-induction-of-cyclooxygenase-2-through-activation-of-the-egfr-p38-mapk-pathway-by-inhibiting-protein-tyrosine-phosphatase-1b-activity
#20
Eiko Yoshida, Masaru Kurita, Komyo Eto, Yoshito Kumagai, Toshiyuki Kaji
Methylmercury is an environmental pollutant that exhibits neurotoxicity when ingested, primarily in the form of neuropathological lesions that localize along deep sulci and fissures, in addition to edematous and inflammatory changes in patient cerebrums. These conditions been known to give rise to a variety of ailments that have come to be collectively termed Minamata disease. Since prostaglandins I2 and E2 (PGI2 and PGE2) increase vascular permeability and contribute to the progression of inflammatory changes, we hypothesize that methylmercury induces the synthesis of these prostaglandins in brain microvascular endothelial cells and pericytes...
September 25, 2017: Toxicology
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