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N-acyl or cannabinoid or NAPE

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https://www.readbyqxmd.com/read/28719234/the-in-vivo-effects-of-the-cb1-positive-allosteric-modulator-gat229-on-intraocular-pressure-in-ocular-normotensive-and-hypertensive-mice
#1
Elizabeth A Cairns, Anna-Maria Szczesniak, Alex J Straiker, Pushkar M Kulkarni, Roger G Pertwee, Ganesh A Thakur, William H Baldridge, Melanie E M Kelly
PURPOSE: Orthosteric cannabinoid receptor 1 (CB1) activation leads to decreases in intraocular pressure (IOP). However, use of orthosteric CB1 agonists chronically has several disadvantages, limiting their usefulness as clinically relevant drugs. Allosteric modulators interact with topographically distinct sites to orthosteric ligands and may be useful to circumvent some of these disadvantages. The purpose of this study was to investigate the effects of the novel CB1-positive allosteric modulator (PAM) GAT229 on IOP...
July 18, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28718196/retracted-cannabinoid-cb-2-receptors-modulate-erk-1-2-kinase-signalling-and-no-release-in-microglial-cells-stimulated-with-bacterial-lipopolysaccharide-by-s-merighi-s-gessi-k-varani-c-simioni-d-fazzi-p-mirandola-and-p-a-borea-british-journal-of-pharmacology
#2
(no author information available yet)
The above article, published by the British Journal of Pharmacology in March 2012 (http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01673.x/full), has been retracted by agreement between the authors, the Journal Editor in Chief and John Wiley & Sons Ltd. The authors wish to state that in preparation of the original manuscript errors occurred resulting in duplication. This issue relates specifically to Figures 2A and 2B, lanes 3-5 of the pJNK1/2 in Figure 3B and lanes 1-3 of the pJNK1/2 blot from Figure 3C...
August 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28717968/deletion-of-type-2-cannabinoid-receptor-induces-alzheimer-s-disease-like-tau-pathology-and-memory-impairment-through-ampk-gsk3%C3%AE-pathway
#3
Lin Wang, Bing-Jin Liu, Yun Cao, Wei-Qi Xu, Dong-Sheng Sun, Meng-Zhu Li, Fang-Xiao Shi, Man Li, Qing Tian, Jian-Zhi Wang, Xin-Wen Zhou
Although several studies have shown that type-2 cannabinoid receptor (CB2R) is involved in Alzheimer's disease (AD) pathology, the effects of CB2R on AD-like tau abnormal phosphorylation and its underlying mechanism remain unclear. Herein, we employed the CB2R(-/-) mice as the animal model to explore roles of CB2R in regulating tau phosphorylation and brain function. We found that CB2R(-/-) mice display AD-like tau hyperphosphorylation, hippocampus-dependent memory impairment, increase of GSK3β activity, decrease of AMPK and Sirt1 activity and mitochondria dysfunction...
July 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28716633/the-synthetic-cannabinoid-win55212-2-ameliorates-traumatic-spinal-cord-injury-via-inhibition-of-gapdh-siah1-in-a-cb2-receptor-dependent-manner
#4
Bin-Xiao Su, Xin Chen, Jia Huo, Shu-Yun Guo, Rui Ma, Yan-Wu Liu
The essential role of GAPDH/Siah1 signaling pathway in the pathogenesis of various injurious conditions such as traumatic spinal cord injury (SCI) has been gradually recognized. However, the drugs targeting this signaling pathway are still lacking. The endocannabinoid system, including its receptors (CB1 and CB2), act as neuroprotective and immunomodulatory modulators in SCI. WIN55212-2, an agonist for CB1 and CB2 receptors, has been demonstrated with anti-inflammatory and anti-apoptotic effects in multiple neurological diseases...
July 14, 2017: Brain Research
https://www.readbyqxmd.com/read/28716266/sativex%C3%A2-effects-on-promoter-methylation-and-on-cnr1-cnr2-expression-in-peripheral-blood-mononuclear-cells-of-progressive-multiple-sclerosis-patients
#5
Massimo Santoro, Massimiliano Mirabella, Chiara De Fino, Assunta Bianco, Matteo Lucchini, Francesco Losavio, Andrea Sabino, Viviana Nociti
Multiple sclerosis (MS) is a chronic demyelinating central nervous system (CNS) disease that involve oligodendrocyte loss and failure to remyelinate damaged brain areas causing a progressive neurological disability. Studies in MS mouse model suggest that cannabinoids ameliorate symptoms as spasticity, tremor and pain reducing inflammation via cannabinoid-mediated system. The aim of our study is to investigate the changes in cannabinoid type 1 (CNR1) and 2 (CNR2) receptors mRNA expression levels and promoter methylation in peripheral blood mononuclear cells (PBMCs) of MS secondary progressive (MSS-SP) patients treated with Sativex®...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28715253/drug-helplines-and-adult-marijuana-users-an-assessment-in-washington-colorado-oregon-and-alaska
#6
Beatriz H Carlini, Sharon B Garrett
Drug helplines are well known and widely utilized resources for those seeking help with managing their substance use. We used "secret shoppers" to preliminarily assess the readiness of drug helplines in four states that legalized non-medical adult marijuana use to assist those seeking information and help for marijuana use. Eleven calls were placed to the helpline staff, where the secret shopper posed as an adult users of marijuana interested in decreasing their marijuana use and asked questions about cannabinoids and methods of marijuana consumption...
July 17, 2017: Substance Abuse
https://www.readbyqxmd.com/read/28715115/membrane-topology-and-identification-of-key-residues-of-eadact-a-plant-mboat-with-unusual-substrate-specificity
#7
Tam N T Tran, Jennifer Shelton, Susan Brown, Timothy P Durrett
Euonymus alatus diacylglycerol acetyltransferase (EaDAcT) catalyzes the transfer of an acetyl group from acetyl-CoA to the sn-3 position of diacylglycerol (DAG) to form 3-acetyl-1,2-diacyl-sn-glycerol (acetyl-TAG). EaDAcT belongs to a small, plant-specific subfamily of the membrane bound O-acyltransferases (MBOAT) that acylate different lipid substrates. Sucrose gradient density centrifugation revealed that EaDAcT colocalizes to the same fractions as an endoplasmic reticulum specific marker. By mapping the membrane topology of EaDAcT, we obtained an experimentally determined topology model for a plant MBOAT...
July 17, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28714993/a-two-helix-motif-positions-the-lysophosphatidic-acid-acyltransferase-active-site-for-catalysis-within-the-membrane-bilayer
#8
Rosanna M Robertson, Jiangwei Yao, Stefan Gajewski, Gyanendra Kumar, Erik W Martin, Charles O Rock, Stephen W White
Phosphatidic acid (PA), the central intermediate in membrane phospholipid synthesis, is generated by two acyltransferases in a pathway conserved in all life forms. The second step in this pathway is catalyzed by 1-acyl-sn-glycerol-3-phosphate acyltransferase, called PlsC in bacteria. Here we present the crystal structure of PlsC from Thermotoga maritima, revealing an unusual hydrophobic/aromatic N-terminal two-helix motif linked to an acyltransferase αβ-domain that contains the catalytic HX4D motif. PlsC dictates the acyl chain composition of the 2-position of phospholipids, and the acyl chain selectivity 'ruler' is an appropriately placed and closed hydrophobic tunnel...
July 17, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28714716/cb%C3%A2-receptor-antagonism-in-the-bed-nucleus-of-the-stria-terminalis-interferes-with-affective-opioid-withdrawal-in-rats
#9
Kiri L Wills, Marieka V DeVuono, Cheryl L Limebeer, Kiran Vemuri, Alexandros Makriyannis, Linda A Parker
The bed nucleus of the stria terminalis (BNST) is a region of the extended amygdala that is implicated in addiction, anxiety, and stress related behaviors. This region has been identified in mediating the aversive state of naloxone-precipitated morphine withdrawal (MWD) and cannabinoid Type I (CB1) receptors have been found to modulate neurotransmission within this region. Previous findings suggest that the CB1 antagonist/inverse agonist, AM251, administered systemically or by infusion into the central nucleus of the amygdala (CeA) prevented the aversive affective properties of MWD as measured by conditioned place aversion learning...
August 2017: Behavioral Neuroscience
https://www.readbyqxmd.com/read/28713595/fatty-acid-profiles-of-stipe-and-blade-from-the-norwegian-brown-macroalgae-laminaria-hyperborea-with-special-reference-to-acyl-glycerides-polar-lipids-and-free-fatty-acids
#10
Lena Foseid, Hanne Devle, Yngve Stenstrøm, Carl Fredrik Naess-Andresen, Dag Ekeberg
A thorough analysis of the fatty acid profiles of stipe and blade from the kelp species Laminaria hyperborea is presented. Lipid extracts were fractionated into neutral lipids, free fatty acids, and polar lipids, prior to derivatization and GC-MS analysis. A total of 42 fatty acids were identified and quantified, including the n-3 fatty acids α-linolenic acid, stearidonic acid, and eicosapentaenoic acid. The fatty acid amounts are higher in blade than in stipe (7.42 mg/g dry weight and 2.57 mg/g dry weight, resp...
2017: Journal of Lipids
https://www.readbyqxmd.com/read/28713291/an-expanding-world-of-novel-psychoactive-substances-opioids
#11
REVIEW
Jolanta B Zawilska
The abuse of novel psychoactive substances (NPS) has been increasing dramatically worldwide since late 2000s. By the end of 2015, more than 560 NPS had been reported to the European Monitoring Centre for Drugs and Drug Addiction. Although the most popular compounds are synthetic cannabinoids and psychostimulatory derivatives of cathinone (so-called β-keto-amphetamines), novel synthetic opioids have recently emerged on the recreational drug market. They include fentanyl (a potent narcotic analgesic) and its analogs (e...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28711691/effects-of-the-2009-medical-cannabinoid-legalization-policy-on-hospital-use-for-cannabinoid-dependency-and-persistent-vomiting
#12
Mustafa Al-Shammari, Karina Herrera, Xibei Liu, Brandon Gisi, Takashi Yamashita, Kyu-Tae Han, Mohamed Azab, Harmeet Mashiana, Muthena Maklad, Muhammad Talha Farooqui, Ranjit Makar, Ji Won Yoo
BACKGROUND & AIMS: In year of 2009, the United States federal Department of Justice issued a memo stating that it would not prosecute users and sellers who complied with the state laws allowing for medical use of marijuana. There are growing concerns about legalization of marijuana use and its related public health effects. We performed an interrupted time series analysis to evaluate these effects. METHODS: We collected a representative sample of hospital discharge data from the healthcare cost and utilization project, from January 1993 through December 2014...
July 12, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28711408/biochemical-characteristics-of-newborns-with-carnitine-transporter-defect-identified-by-newborn-screening-in-california
#13
N M Gallant, K Leydiker, Y Wilnai, C Lee, F Lorey, L Feuchtbaum, H Tang, J Carter, G M Enns, S Packman, H J Lin, W R Wilcox, S D Cederbaum, J E Abdenur
Carnitine transporter defect (CTD; also known as systemic primary carnitine deficiency; MIM 212140) is due to mutations in the SLC22A5 gene and leads to extremely low carnitine levels in blood and tissues. Affected individuals may develop early onset cardiomyopathy, weakness, or encephalopathy, which may be serious or even fatal. The disorder can be suggested by newborn screening. However, markedly low newborn carnitine levels can also be caused by conditions unrelated to CTD, such as the low carnitine levels often associated with normal pregnancies and some metabolic disorders occurring in the mother...
July 8, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28710683/highly-selective-cb2-receptor-agonist-a836339-has-gastroprotective-effect-on-experimentally-induced-gastric-ulcers-in-mice
#14
M Salaga, H Zatorski, M Zielińska, P Mosinska, J-P Timmermans, R Kordek, M Storr, J Fichna
Cannabinoid type 2 (CB2) receptors are distributed in central and peripheral tissues, including immunocytes and the gastrointestinal (GI) tract, suggesting that CB2 receptor agonists represent potential therapeutics in GI inflammatory states. In this study, we investigated the effect of highly selective CB2 agonist, A836339, on the development of gastric lesions. We used two models of gastric ulcer (GU) induced by ethanol (EtOH) and diclofenac. To confirm the involvement of CB2 receptors, a selective CB2 antagonist, AM630 was used...
July 14, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28708388/nickel-catalyzed-alkene-carboacylation-via-activation-of-amide-c-n-bonds
#15
James A Walker, Kevin L Vickerman, Jenna N Humke, Levi M Stanley
We report nickel-catalyzed formal carboacylation of ortho-allylbenzamides with arylboronic acid pinacol esters. These carboacylation reactions are triggered by the oxidative addition of an activated amide C-N bond to a nickel(0) catalyst and proceed via alkene insertion into a nickel(II)-acyl bond. The exo-selective carboacylation reactions generate 2-benzyl-2,3-dihydro-1H-inden-1-ones in moderate-to-high yields (46-99%) from a variety of arylboronic acid pinacol esters and substituted ortho-allylbenzamides...
July 14, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28707583/cannabis-an-overview-of-its-adverse-acute-and-chronic-effects-and-their-implications
#16
Talitha C Ford, Amie C Hayley, Luke A Downey, Andrew C Parrott
In many communities, cannabis is perceived as a low-risk drug, leading to political lobbying to decriminalise its use. However, acute and chronic cannabis use has been shown to be harmful to several aspects of psychological and physical health, such as mood states, psychiatric outcomes, neurocognition, driving and general health. Furthermore, cannabis is highly addictive, and the adverse effects of withdrawal can lead to regular use. These in turn have adverse implications for public safety and health expenditure...
July 12, 2017: Current Drug Abuse Reviews
https://www.readbyqxmd.com/read/28707493/ab-chminaca-induced-sudden-death-from-non-cardiogenic-pulmonary-edema
#17
Hideyuki Maeda, Ruri Kikura-Hanajiri, Maiko Kawamura, Erika Nagashima, Ken-Ichi Yoshida
CONTEXT: Despite widespread use of diverse synthetic cannabinoid (sCB) compounds, the pathophysiology associated with intoxication with many sCB compounds, including AB-CHMINACA, is poorly understood, as is their metabolism and distribution into blood and organs. CASE DETAILS: A young man died shortly after ingesting an herb product containing sCB compounds. Toxicological analyses of blood samples revealed high levels of AB-CHMINACA (7.61 ± 0.59 ng/mL) and its metabolites (M2, 56...
July 14, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28706566/motor-vehicle-collisions-caused-by-the-super-strength-synthetic-cannabinoids-mam-2201-5f-pb-22-5f-ab-pinaca-5f-amb-and-5f-adb-in-japan-experienced-from-2012-to-2014
#18
REVIEW
Shuji Kaneko
From 2012 to 2014 in Japan, 214 cases of motor vehicle collisions were attributed to the use of illegal drugs. In 93 out of 96 investigated cases, the causative agents were a variety of synthetic cannabinoids (SCs). These SCs can be classified into three groups according to the lineage of the chemical structures: (1) naphthoyl indoles, such as MAM-2201, (2) quinolinyl ester indoles, such as 5F-PB-22, and (3) indazole carboxamides, such as 5F-AB-PINACA, 5F-AMB, and 5F-ADB. These SCs became available sequentially with increasing cannabinoid CB1 agonist potencies and reached a nationwide outbreak in the summer of 2014...
2017: Forensic Toxicology
https://www.readbyqxmd.com/read/28706006/integration-of-flux-measurements-to-resolve-changes-in-anabolic-and-catabolic-metabolism-in-cardiac-myocytes
#19
Andrew A Gibb, Pawel K Lorkiewicz, Yu-Ting Zheng, Xiang Zhang, Aruni Bhatnagar, Steven P Jones, Bradford G Hill
Although ancillary pathways of glucose metabolism are critical for synthesizing cellular building blocks and modulating stress responses, how they are regulated remains unclear.  In this study, we used radiometric glycolysis assays, [(13)C6]-glucose isotope tracing, and extracellular flux analysis to understand how phosphofructokinase (PFK)-mediated changes in glycolysis regulate glucose carbon partitioning into catabolic and anabolic pathways. Expression of kinase-deficient or phosphatase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in rat neonatal cardiomyocytes coordinately regulated glycolytic rate and lactate production...
July 13, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28705172/endocannabinoid-receptor-blockade-reduces-alanine-aminotransferase-in-polycystic-ovary-syndrome-independent-of-weight-loss
#20
Alison J Dawson, Eric S Kilpatrick, Anne-Marie Coady, Abeer M M Elshewehy, Youssra Dakroury, Lina Ahmed, Stephen L Atkin, Thozhukat Sathyapalan
BACKGROUND: Evidence suggests that endocannabinoid system activation through the cannabinoid receptor 1 (CB1) is associated with enhanced liver injury, and CB1 antagonism may be beneficial. The aim of this study was to determine the impact of rimonabant (CB1 antagonist) on alanine aminotransferase (ALT), a hepatocellular injury marker, and a hepatic inflammatory cytokine profile. METHODS: Post hoc review of 2 studies involving 50 obese women with PCOS and well matched for weight, randomised to weight reducing therapy; rimonabant (20 mg od) or orlistat (120 mg tds), or to insulin sensitising therapy metformin, (500 mg tds), or pioglitazone (45 mg od)...
July 14, 2017: BMC Endocrine Disorders
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