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https://www.readbyqxmd.com/read/28327676/management-of-organophosphorus-poisoning
#1
S R Bajracharya, P N Prasad, R Ghimire
Organophosphorus (OP) compounds are widely used for agriculture, domestic pest-control and chemical warfare. Pesticide self-poisoning accounts for one-sixth to one-eighth of the world's suicides and a third of suicide deaths in rural Asia each year. OP pesticides inhibit cholinesterase enzymes leading to overstimulation of cholinergic receptors. Clinical features depend on the types of receptors stimulated at various sites of the body. The diagnosis of OP poisoning is made on the basis of history of poisoning, smell of pesticides, the characteristic clinical signs and reduced cholinesterase activity...
September 2016: Journal of Nepal Health Research Council
https://www.readbyqxmd.com/read/28326551/cyclic-imine-toxins-from-dinoflagellates-a-growing-family-of-potent-antagonists-of-the-nicotinic-acetylcholine-receptors
#2
REVIEW
Jordi Molgó, Pascale Marchot, Rómulo Aráoz, Evelyne Benoit, Bogdan I Iorga, Armen Zakarian, Palmer Taylor, Yves Bourne, Denis Servent
We present an overview of the toxicological profile of the fast-acting, lipophilic macrocyclic imine toxins, an emerging family of organic compounds associated with algal blooms, shellfish contamination and neurotoxicity. Worldwide, shellfish contamination incidents are expanding; therefore, the significance of these toxins for the shellfish food industry deserves further study. Emphasis is directed to the dinoflagellate species involved in their production, their chemical structures, and their specific mode of interaction with their principal natural molecular targets, the nicotinic acetylcholine receptors, or with the soluble acetylcholine-binding protein, used as a surrogate receptor model...
March 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28326549/the-three-finger-toxin-fold-a-multifunctional-structural-scaffold-able-to-modulate-cholinergic-functions
#3
REVIEW
Pascal Kessler, Pascale Marchot, Marcela Silva, Denis Servent
Three-finger fold toxins are miniproteins frequently found in Elapidae snake venoms. This fold is characterized by three distinct loops rich in β-strands and emerging from a dense, globular core reticulated by four highly conserved disulfide bridges. The number and diversity of receptors, channels, and enzymes identified as targets of three-finger fold toxins is increasing continuously. Such manifold diversity highlights the specific adaptability of this fold for generating pleiotropic functions. Although this toxin superfamily disturbs many biological functions by interacting with a large diversity of molecular targets, the most significant target is the cholinergic system...
March 21, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28325810/correction-to-differential-contribution-of-subunit-interfaces-to-a9a10-nicotinic-acetylcholine-receptor-function
#4
(no author information available yet)
No abstract text is available yet for this article.
May 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28321180/multiple-kinases-involved-in-the-nicotinic-modulation-of-gamma-oscillations-in-the-rat-hippocampal-ca3-area
#5
JianGang Wang, XiaoLong He, Fangli Guo, XiangLin Cheng, Yali Wang, XiaoFang Wang, ZhiWei Feng, Martin Vreugdenhil, ChengBiao Lu
Neuronal synchronization at gamma band frequency (20-80 Hz, γ oscillations) is closely associated with higher brain function, such as learning, memory and attention. Nicotinic acetylcholine receptors (nAChRs) are highly expressed in the hippocampus, and modulate hippocampal γ oscillations, but the intracellular mechanism underlying such modulation remains elusive. We explored multiple kinases by which nicotine can modulate γ oscillations induced by kainate in rat hippocampal area CA3 in vitro. We found that inhibitors of cyclic AMP dependent kinase (protein kinase A, PKA), protein kinase C (PKC), N-methyl-D-aspartate receptor (NMDA) receptors, Phosphoinositide 3-kinase (PI3K) and extracellular signal-related kinases (ERK), each individually could prevent the γ oscillation-enhancing effect of 1 μM nicotine, whereas none of them affected baseline γ oscillation strength...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28319594/long-term-cardiovascular-autonomic-and-clinical-changes-after-immunoglobulin-g-immunoadsorption-therapy-in-autoimmune-autonomic-ganglionopathy
#6
Franca Barbic, Franca Dipaola, Francesca Andreetta, Enrico Brunetta, Laura Dalla Vecchia, Renato Mantegazza, Raffaello Furlan, Carlo Antozzi
A 63-year-old male was diagnosed with autoimmune autonomic ganglionopathy based on the finding of plasma antibodies to the nicotinic acetylcholine receptor (nAChR) of autonomic ganglia. He complained of mouth and eye dryness, dysphagia, severe constipation, erectile dysfunction, urgency, frequent urination, habitual orthostatic syncope and presyncope. A remarkable symptomatic orthostatic hypotension without changes in heart rate was present. We here describe the 3-year time course of the changes in spectral indices of cardiovascular autonomic control LF/HF and LFSAP, dysautonomia symptoms intensity and anti-nAChR antibodies following repetitive selective immunoadsorptions...
March 17, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28315314/nicotine-promotes-cholangiocarcinoma-growth-in-xenograft-mice
#7
Allyson K Martínez, Kendal Jensen, Chad Hall, April O'Brien, Laurent Ehrlich, Tori White, Fanyin Meng, Tianhao Zhou, John Greene, Francesca Bernuzzi, Pietro Invernizzi, David E Dostal, Terry Lairmore, Gianfranco Alpini, Shannon Glaser
Nicotine, the main addictive substance in tobacco, is known to play a role in the development and/or progression of a number of malignant tumors. However, nicotine's involvement in the pathogenesis of cholangiocarcinoma is controversial. Therefore, we studied the effects of nicotine on the growth of cholangiocarcinoma cells in vitro and the progression of cholangiocarcinoma in a mouse xenograft model. The predominant subunit responsible for nicotine-mediated proliferation in normal and cancer cells, the α7 nicotinic acetylcholine receptor (α7-nAChR), was more highly expressed in human cholangiocarcinoma cell lines compared with normal human cholangiocytes...
March 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28315274/role-of-%C3%AF-1-receptors-in-learning-and-memory-and-alzheimer-s-disease-type-dementia
#8
Tangui Maurice, Nino Goguadze
The present chapter will review the role of σ1 receptor in learning and memory and neuroprotection , against Alzheimer's type dementia. σ1 Receptor agonists have been tested in a variety of pharmacological and pathological models of learning impairments in rodents these last past 20 years. Their anti-amnesic effects have been explained by the wide-range modulatory role of σ1 receptors on Ca(2+) mobilizations, neurotransmitter responses, and particularly glutamate and acetylcholine systems, and neurotrophic factors...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28314679/an-analysis-of-the-rewarding-and-aversive-associative-properties-of-nicotine-in-the-neonatal-quinpirole-model-effects-on-glial-cell-line-derived-neurotrophic-factor-gdnf
#9
Russell W Brown, Seth L Kirby, Adam R Denton, John M Dose, Elizabeth D Cummins, Wesley Drew Gill, Katherine C Burgess
This study analyzed the associative properties of nicotine in a conditioned place preference (CPP) paradigm in adolescent rats neonatally treated with quinpirole (NQ) or saline (NS). NQ produces dopamine D2 receptor supersensitivity that persists throughout the animal's lifetime, and therefore has relevance towards schizophrenia. In two experiments, rats were ip administered quinpirole (1mg/kg) or saline from postnatal day (P)1-21. After an initial preference test at P42-43, animals were conditioned for eight consecutive days with saline or nicotine (0...
March 14, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28306606/spinal-microglial-p2x4-receptor-brain-derived-neurotrophic-factor-signaling-regulates-nicotine-withdrawal-induced-hyperalgesia
#10
Xiaodi Zhang, Pengcheng Xu, Chengbao Li, Wenchao Zhu, Shanshan Wu, Ailan Yu, Yonghong Ding, Qinghe Wang, Zongwang Zhang
Nicotine withdrawal (NTW) has been shown to increase pain sensitivity. However, the pathogenesis of NTW-induced hyperalgesia syndrome is unknown. Microglial activation, with increased expression of the P2X4 receptor (P2X4R) and brain-derived neurotrophic factor (BDNF) as important markers, is associated with hyperalgesia; therefore, these markers may represent an unprecedented target to prevent hyperalgesia. In this study, we explored the contributions of spinal microglial P2X4R-BDNF signaling in NTW-induced hyperalgesia...
March 16, 2017: Neuroreport
https://www.readbyqxmd.com/read/28302571/alpha-9-nicotinic-acetylcholine-receptors-mediate-hypothermic-responses-elicited-by-provocative-motion-in-mice
#11
Longlong Tu, Lauren Poppi, John Rudd, Ethan T Cresswell, Doug W Smith, Alan Brichta, Eugene Nalivaiko
Hypothermic responses accompany motion sickness in humans and can be elicited by provocative motion in rats. We aimed to determine the potential role in these responses of the efferent cholinergic vestibular innervation. To this end, we used knockout (KO) mice lacking α9 cholinoreceptor subunit predominantly expressed in the vestibular hair cells and CBA strain as a wild-type (WT) control. In WT mice, circular horizontal motion (1Hz, 4cm radius, 20min) caused rapid and dramatic falls in core body temperature and surface head temperature associated with a transient rise in the tail temperature; these responses were substantially attenuated in KO mice; changes were (WT vs...
March 14, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28302458/the-effects-of-dexmedetomidine-pretreatment-on-the-pro-and-anti-inflammation-systems-after-spinal-cord-injury-in-rats
#12
Hui Rong, Zhibin Zhao, Jiying Feng, Yishan Lei, Hao Wu, Rao Sun, Zuoxia Zhang, Bailing Hou, Wei Zhang, YuE Sun, Xiaoping Gu, Zhengliang Ma, Yue Liu
Excessive inflammatory responses play important roles in the aggravation of secondary damage to an injured spinal cord. Dexmedetomidine (DEX), a selective α2-adrenoceptor agonist, has recently been implied to be neuroprotective in clinical anesthesia, but the underlying mechanism is elusive. As signaling through Toll-like receptor 4 (TLR4) and nicotinic receptors (nAChRs, notably α7nAChR) play important roles in the pro- and anti-inflammation systems in the central nervous system, respectively, this study investigated whether and how they were modulated by DEX pretreatment in a rat model of spinal cord compression...
March 14, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28302035/translational-multimodality-neuroimaging
#13
Sushil K Sharma
Recently high-resolution, noninvasive, multimodality in-vivo molecular imaging with PET, SPECT, CT and MRI, employing fusion algorithms has revolutionized personalized medicine. However, specific radiopharmaceuticals (RPs) for the accurate diagnosis and effective treatment of progressive neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, drug addiction, and other cognitive impairments still remain in developmental phase. Currently, multimodality fusion neuroimaging is utilized for the determination of: pharmacokinetics and pre-clinical development of radiopharmaceuticals (RPs); in-vivo monitoring of stem cell transplantation therapy; nicotinic acetylcholine receptors (nAChRs) investigations; and regional cerebral blood flow and glucose metabolism in cognitively-impaired subjects employing noninvasive microPET and nano-SPECT imaging...
March 15, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28298165/high-throughput-patch-clamp-screening-in-human-%C3%AE-6-containing-nicotinic-acetylcholine-receptors
#14
Lucas C Armstrong, Glenn E Kirsch, Nikolai B Fedorov, Caiyun Wu, Yuri A Kuryshev, Abby L Sewell, Zhiqi Liu, Arianne L Motter, Carmine S Leggett, Michael S Orr
Nicotine, the addictive component of tobacco products, is an agonist at nicotinic acetylcholine receptors (nAChRs) in the brain. The subtypes of nAChR are defined by their α- and β-subunit composition. The α6β2β3 nAChR subtype is expressed in terminals of dopaminergic neurons that project to the nucleus accumbens and striatum and modulate dopamine release in brain regions involved in nicotine addiction. Although subtype-dependent selectivity of nicotine is well documented, subtype-selective profiles of other tobacco product constituents are largely unknown and could be essential for understanding the addiction-related neurological effects of tobacco products...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28296947/the-dual-orexin-receptor-antagonist-tcs1102-does-not-affect-reinstatement-of-nicotine-seeking
#15
Shaun Yon-Seng Khoo, Gavan P McNally, Kelly J Clemens
The orexin/hypocretin system is important for appetitive motivation towards multiple drugs of abuse, including nicotine. Both OX1 and OX2 receptors individually have been shown to influence nicotine self-administration and reinstatement. Due to the increasing clinical use of dual orexin receptor antagonists in the treatment of disorders such as insomnia, we examined whether a dual orexin receptor antagonist may also be effective in reducing nicotine seeking. We tested the effect of intracerebroventricular (i...
2017: PloS One
https://www.readbyqxmd.com/read/28294298/proteins-and-chemical-chaperones-involved-in-neuronal-nicotinic-receptor-expression-and-function-an-update
#16
REVIEW
Arianna Crespi, Sara Francesca Colombo, Cecilia Gotti
Neuronal nicotinic acetylcholine receptors (nAChRs) are a family of acetylcholine-(ACh) gated cation channels and their homeostasis or proteostasis is essential for the correct physiology of the central and peripheral nervous systems. The proteostasis network regulates the folding, assembly, degradation and trafficking of nAChRs in order to ensure their efficient functional cell surface expression. However, as nAChRs are multisubunit, multispan, integral membrane proteins, the folding and assembly is a very inefficient process, and only a small portion of subunits can form functional pentamers...
March 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28293176/muscarinic-receptors-are-responsible-for-the-cholinergic-modulation-of-projection-neurons-in-the-song-production-brain-nucleus-ra-of-zebra-finches
#17
Wei Meng, Songhua Wang, Lihua Yao, Nan Zhang, Dongfeng Li
Songbirds are a useful model for the study of learned vocal behavior in vertebrates. The robust nucleus of the arcopallium (RA) is a premotor nucleus in the vocal motor pathway. It receives excitatory synaptic inputs from the anterior forebrain pathway. RA also receives cholinergic inputs from the ventral paleostriatum of the basal forebrain. Our previous study showed that carbachol, a non-selective cholinergic receptor agonist, modulates the electrophysiology of RA projection neurons (PNs), indicating that cholinergic modulation of RA may play an important role in song production...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28290528/nicotine-dependence-is-associated-with-functional-variation-in-fmo3-an-enzyme-that-metabolizes-nicotine-in-the-brain
#18
A M Teitelbaum, S E Murphy, G Akk, T B Baker, A Germann, L B von Weymarn, L J Bierut, A Goate, E D Kharasch, A J Bloom
A common haplotype of the flavin-containing monooxygenase gene FMO3 is associated with aberrant mRNA splicing, a twofold reduction in in vivo nicotine N-oxidation and reduced nicotine dependence. Tobacco remains the largest cause of preventable mortality worldwide. CYP2A6, the primary hepatic nicotine metabolism gene, is robustly associated with cigarette consumption but other enzymes contribute to nicotine metabolism. We determined the effects of common variants in FMO3 on plasma levels of nicotine-N-oxide in 170 European Americans administered deuterated nicotine...
March 14, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28288805/humoral-immunity-and-autism-spectrum-disorders
#19
Keith Fluegge
Abnormal immune activation, particularly of a humoral nature, has consistently been described in the etiopathogenesis of autism spectrum disorders (ASD). In this journal, Mead and Ashwood (2015) reviewed immune abnormalities in autism and linked them to severity of classic autistic symptoms. However, there remains a lack of clarity as to how environmental risk factors in ASD may contribute to such immunophenotypes. The evidence presented herein highlights these immune deficits of a humoral nature in ASD. Moreover, aligned with prior research showing a link between chronic air pollution and suppression of humoral immunity, the author of this commentary has proposed that environmental exposure to pervasive air pollutants, particularly nitrous oxide (N2O), may target several anti-inflammatory biomarkers, including alpha 7 nicotinic acetylcholine receptor (α7nAChR) inhibition and stimulation of kappa opioid receptor (KOR) activity...
March 10, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28287260/probing-for-and-quantifying-agonist-hydrogen-bonds-in-%C3%AE-6%C3%AE-2-nicotinic-acetylcholine-receptors
#20
Michael R Post, Henry A Lester, Dennis A Dougherty
Designing subtype-selective agonists for neuronal nicotinic acetylcholine receptors is a challenging and significant goal aided by intricate knowledge of each subtype's binding patterns. We previously reported that in α6β2 receptors, acetylcholine makes a functional cation-π interaction with Trp149, but nicotine and TC299423 do not, suggesting a distinctive binding site. This work explores hydrogen binding at the backbone carbonyl associated with α6β2 Trp149. Substituting residue i + 1, Thr150, with its α-hydroxy analogue (Tah) attenuates the carbonyl's hydrogen bond accepting ability...
March 21, 2017: Biochemistry
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