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https://www.readbyqxmd.com/read/27917870/high-frequency-stimulation-of-the-subthalamic-nucleus-blocks-compulsive-like-re-escalation-of-heroin-taking-in-rats
#1
Carrie L Wade, Marsida Kallupi, Daniel O Hernandez, Emmanuel Breysse, Giordano de Guglielmo, Elena Crawford, George F Koob, Paul Schweitzer, Christelle Baunez, Olivier George
Opioid addiction, including addiction to heroin, has dramatically increased in the last decade. The cost and pervasiveness of heroin addiction, including resistance to recovery from addiction, provide a compelling basis for developing novel therapeutic strategies. Deep brain stimulation may represent a viable alternative strategy for the treatment of intractable heroin addiction particularly in individuals who are resistant to traditional therapies. Here, we provide preclinical evidence of the therapeutic potential of high-frequency stimulation of the subthalamic nucleus (STN HFS) for heroin addiction...
December 5, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27909407/the-tlr4-active-morphine-metabolite-morphine-3-glucuronide-does-not-elicit-macrophage-classical-activation-in-vitro
#2
Samira Khabbazi, Nan Xie, Wenjun Pu, Yannick Goumon, Marie-Odile Parat
Macrophages are abundant in the tumor microenvironment where they adopt a pro-tumor phenotype following alternative polarization induced by paracrine factors from cancer and stromal cells. In contrast, classically activated macrophages have tumoricidal activities, such that the polarization of tumor-associated macrophages has become a novel therapeutic target. Toll-like receptor 4 engagement promotes classical activation of macrophages, and recent literature suggests TLR4 agonism to prevent metastasis and promote survival in experimental metastasis models...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27903758/oprm1-and-comt-gene-gene-interaction-is-associated-with-postoperative-pain-and-opioid-consumption-after-orthopedic-trauma
#3
Heba Khalil, Susan M Sereika, Feng Dai, Sheila Alexander, Yvette Conley, Gary Gruen, Li Meng, Peter Siska, Ivan Tarkin, Richard Henker
BACKGROUND: mu-opioid receptor (OPRM1) and catechol-O-methyltransferase (COMT) contribute to the neurotransmission pathway of pain. COMT affects mu receptor expression and density in the brain. The aim of this study was to explore the OPRM1 and COMT interaction effects on postoperative pain and opioid consumption. METHODS: This cross-sectional exploratory study used genotype and clinical data from 153 postoperative patients. Using multiple regression analyses, four single-nucleotide polymorphisms of COMT (rs6269, rs4633, rs4818, and rs4680), their haplotypes, and diplotypes were considered for their interactions with A118G of OPRM1 regarding postoperative pain and opioid consumption...
November 30, 2016: Biological Research for Nursing
https://www.readbyqxmd.com/read/27899254/thalidomide-attenuates-the-development-and-expression-of-antinociceptive-tolerance-to-%C3%AE-opioid-agonist-morphine-through-l-arginine-inos-and-nitric-oxide-pathway
#4
Muhammad Imran Khan, Sattar Ostadhadi, Faiza Mumtaz, Majid Momeny, Farima Moghaddaskho, Mahsa Hassanipour, Shahram Ejtemaei-Mehr, Ahmad Reza Dehpour
Morphine is a μ-opioid analgesic drug which is used in the treatment and management of chronic pain. However, due to development of antinociceptive tolerance its clinical use is limited. Thalidomide is an old glutamic acid derivative which recently reemerged because of its potential to counteract a number of disorders including neurodegenerative disorders. The potential underlying mechanisms and effects of thalidomide on morphine-induced antinociceptive tolerance is still elusive. Hence, the present study was designed to explore the effect of thalidomide on the development and expression of morphine antinociceptive tolerance targeting l-arginine-nitric oxide (NO) pathway in mice and T98G human glioblastoma cell line...
November 26, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27890744/gene-expression-of-pro-opiomelanocortin-and-melanocortin-receptors-is-regulated-in-the-hypothalamus-and-mesocorticolimbic-system-following-nicotine-administration
#5
Damla E Tapinc, Rabia Ilgin, Egemen Kaya, Oguz Gozen, Muzeyyen Ugur, Ersin O Koylu, Lutfiye Kanit, Aysegul Keser, Burcu Balkan
Pro-opiomelanocortin (POMC)-derived peptides and their receptors have been shown to play important roles in natural and drug-induced reward and reinforcement. Reward process may involve the regulation of POMC gene expression and the gene expression of POMC-derived peptide receptors. The present study investigated the alterations observed in the transcript levels of POMC, melanocortin 3 (MC3R), melanocortin 4 (MC4R) and mu-opioid receptors (MOR) in the hypothalamus and mesocorticolimbic system during nicotine exposure...
November 24, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27883323/association-of-single-nucleotide-polymorhism-c3435t-in-the-abcb1-gene-with-opioid-sensitivity-in-treatment-of-postoperative-pain
#6
Vanja Dzambazovska-Trajkovska, Jordan Nojkov, Andrijan Kartalov, Biljana Kuzmanovska, Tatjana Spiroska, Redzep Seljmani, Gjorgji Trajkovski, Nadica Matevska-Geshkovska, Aleksandar Dimovski
BACKGROUND: The minimal effective analgesic concentration of opioids required for satisfactory analgesia may differ significantly among the patients. Genetic factors may contribute to the variable response to opioids by affecting their pharmacokinetics or pharmacodynamics. METHODS: Ninety nine patients undergoing abdominal surgery with colorectal anastomosis because of colorectal carcinoma were enrolled in the present study. C34535T was genotyped in all subjects and the patients were divided into three groups according to their genotype: CC-wild type homozygous, CT-mutant heterozygous and TT-mutant homozygous...
November 1, 2016: Prilozi (Makedonska Akademija Na Naukite i Umetnostite. Oddelenie za Medicinski Nauki)
https://www.readbyqxmd.com/read/27870427/understanding-the-broad-influence-of-sex-hormones-and-sex-differences-in-the-brain
#7
REVIEW
Bruce S McEwen, Teresa A Milner
Sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Sex hormones can act through many cellular and molecular processes that alter structure and function of neural systems and influence behavior as well as providing neuroprotection. Within neurons, sex hormone receptors are found in nuclei and are also located near membranes, where they are associated with presynaptic terminals, mitochondria, spine apparatus, and postsynaptic densities. Sex hormone receptors also are found in glial cells...
January 2, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/27836661/phosphorylation-of-poly-rc-binding-protein-1-pcbp1-contributes-to-stabilization-of-mu-opioid-receptor-mor-mrna-via-interaction-with-au-rich-element-rna-binding-protein-1-auf1-and-poly-a-binding-protein-pabp
#8
Cheol Kyu Hwang, Yadav Wagley, Ping-Yee Law, Li-Na Wei, Horace H Loh
Gene regulation at the post-transcriptional level is frequently based on cis- and trans-acting factors on target mRNAs. We found a C-rich element (CRE) in mu-opioid receptor (MOR) 3'-untranslated region (UTR) to which poly (rC) binding protein 1 (PCBP1) binds, resulting in MOR mRNA stabilization. RNA immunoprecipitation and RNA EMSA revealed the formation of PCBP1-RNA complexes at the element. Knockdown of PCBP1 decreased MOR mRNA half-life and protein expression. Stimulation by forskolin increased cytoplasmic localization of PCBP1 and PCBP1/MOR 3'-UTR interactions via increased serine phosphorylation that was blocked by protein kinase A (PKA) or (phosphatidyl inositol-3) PI3-kinase inhibitors...
November 9, 2016: Gene
https://www.readbyqxmd.com/read/27831648/a-personalized-approach-identifies-disturbed-pathways-and-key-genes-in-hepatitis-c-virus-cirrhosis-with-hepatocellular-carcinoma
#9
Y-G Li, M-X Zheng, G Wang
OBJECTIVE: This work aimed to identify disturbed pathways in hepatitis C virus (HCV)-cirrhosis with hepatocellular carcinoma (HCC) based on individualized pathway aberrance score (iPAS) method. MATERIALS AND METHODS: First of all, gene expression data and pathway data were recruited and preprocessed. Next, iPAS method, which contained three steps (gene-level statistics based on average Z algorithm, pathway-level statistics and pathway significant analysis based on Wilcoxon-test), was performed to identify differential pathways in HCV-cirrhosis with HCC...
October 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27819333/novel-toll-like-receptor-4-antagonist-naloxone-protects-mice-from-inflammation-induced-preterm-birth
#10
Peck Yin Chin, Camilla L Dorian, Mark R Hutchinson, David M Olson, Kenner C Rice, Lachlan M Moldenhauer, Sarah A Robertson
Toll-like receptor 4 (TLR4) activation by bacterial infection, or by sterile inflammatory insult is a primary trigger of spontaneous preterm birth. Here we utilize mouse models to investigate the efficacy of a novel small molecule TLR4 antagonist, (+)-naloxone, the non-opioid isomer of the opioid receptor antagonist (-)-naloxone, in infection-associated preterm birth. Treatment with (+)-naloxone prevented preterm delivery and alleviated fetal demise in utero elicited by i.p. LPS administration in late gestation...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27819122/erratum-to-carriers-of-genetic-variants-in-the-hnf1a-gene-are-more-common-among-dead-opioid-addicts-than-among-living-addicts
#11
Anh Nguyen, Tore B Stage, Søren Feddersen, Dorte J Christoffersen, Mette Marie H Christensen, Per Damkier, Jørgen L Thomsen, Kim Brøsen
No abstract text is available yet for this article.
November 7, 2016: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27813192/naltrexone-changes-the-expression-of-lipid-metabolism-related-proteins-in-the-endoplasmic-reticulum-er-stress-induced-hepatic-steatosis-in-mice
#12
Azam Moslehi, Fatemeh Nabavizadeh, Ali Zekri, Fatemeh Amiri
Endoplasmic reticulum (ER) stress is closely associated with several chronic diseases such as obesity, atherosclerosis, type 2 diabetes, and hepatic steatosis. Steatosis in hepatocytes may also lead to disorders such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), fibrosis, and possibly cirrhosis. Opioid peptides are involved in triglyceride and cholesterol dysregulation. Naltrexone also attenuates ER stress induced hepatic steatosis in mice. In this study, we evaluated the effects of naltrexone on the expression of lipid metabolism-related nuclear factors and enzymes in the ER stress induced hepatic steatosis...
November 4, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27802429/kappa-opioid-agonist-u50-488h-mediated-protection-against-heart-failure-following-myocardial-ischemia-reperfusion-dual-roles-of-heme-oxygenase-1
#13
Guang Tong, Ben Zhang, Xuan Zhou, Jinbo Zhao, Zhongchan Sun, Ye Tao, Jianming Pei, Weida Zhang
BACKGROUNDS/AIMS: The selective κ-opioid agonist U50,488H protects heart from myocardial ischemia-reperfusion (MI/R) injury. We examined whether U50,488H is also beneficial for MI/R induced heart failure. METHODS: Anesthetized male Sprague-Dawley rats were subjected to 30 min of myocardial ischemia via left anterior descending coronary artery (LAD) occlusion, followed by 4 weeks of reperfusion. Infarct size was examined by Evans blue/triphenyl tetrazolium chloride (TTC) staining...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27778232/a-computational-systems-biology-approach-for-identifying-candidate-drugs-for-repositioning-for-cardiovascular-disease
#14
Alvin Z Yu, Stephen A Ramsey
We report an in silico method to screen for receptors or pathways that could be targeted to elicit beneficial transcriptional changes in a cellular model of a disease of interest. In our method, we integrate: (1) a dataset of transcriptome responses of a cell line to a panel of drugs; (2) two sets of genes for the disease; and (3) mappings between drugs and the receptors or pathways that they target. We carried out a gene set enrichment analysis (GSEA) test for each of the two gene sets against a list of genes ordered by fold-change in response to a drug in a relevant cell line (HL60), with the overall score for a drug being the difference of the two enrichment scores...
October 24, 2016: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/27762075/sex-specific-linkage-scans-in-opioid-dependence
#15
Bao-Zhu Yang, Shizhong Han, Henry R Kranzler, Abraham A Palmer, Joel Gelernter
Sex influences risk for opioid dependence (OD). We hypothesized that sex might interact with genetic loci that influence the risk for OD. Therefore we performed an analysis to identify sex-specific genomic susceptibility regions for OD using linkage. Over 6,000 single nucleotide polymorphism (SNP) markers were genotyped for 1,758 African- and European-American (AA and EA) individuals from 739 families, ascertained via affected sib-pairs with OD and/or cocaine dependence. Autosomewide non-parametric linkage scans, stratified by sex and population, were performed...
October 20, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/27756950/role-of-fosaprepitant-a-neurokinin-type-1-receptor-antagonist-in-morphine-induced-antinociception-in-rats
#16
Pranav Prasoon, Shivani Gupta, Rahul Kumar, Mayank Gautam, Saroj Kaler, Subrata Basu Ray
OBJECTIVES: Opioids such as morphine form the cornerstone in the treatment of moderate to severe pain. However, opioids also produce serious side effects such as tolerance. Fosaprepitant is a substance P (SP) receptor antagonist, which is used for treating chemotherapy-induced nausea and vomiting. SP is an important neuropeptide mediating transmission of pain at the spinal level. Thus, it was hypothesized that combining morphine with fosaprepitant would increase the antinociceptive effect of morphine...
July 2016: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/27754186/sp-04-1-the-role-of-natriuretic-peptides-in-the-pathogenesis-of-cardiovascular-diseases
#17
Zhanna Kobalava
The burden of cardiovascular diseases (CVD) in general and heart failure (HF) in particular continues to increase worldwide. CVD are major contributors to death and morbidity and recognized as important drivers of healthcare expenditure. Chronic overactivity of the renin-angiotensin-aldosterone system (RAAS) plays a key role in human hypertension and HF pathophysiology. RAAS is fundamental in the overall regulation of cardiovascular homeostasis through the actions of hormones, which regulate vascular tone, and specifically blood pressure through vasoconstriction and renal sodium and water retention...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27752976/pharmacogenomics-and-pharmacogenetics-for-the-intensive-care-unit-a-narrative-review
#18
Meghan MacKenzie, Richard Hall
PURPOSE: Knowledge of how alterations in pharmacogenomics and pharmacogenetics may affect drug therapy in the intensive care unit (ICU) has received little study. We review the clinically relevant application of pharmacogenetics and pharmacogenomics to drugs and conditions encountered in the ICU. SOURCE: We selected relevant literature to illustrate the important concepts contained within. PRINCIPAL FINDINGS: Two main approaches have been used to identify genetic abnormalities - the candidate gene approach and the genome-wide approach...
October 17, 2016: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/27749013/high-motivation-for-exercise-is-associated-with-altered-chromatin-regulators-of-monoamine-receptor-gene-expression-in-the-striatum-of-selectively-bred-mice
#19
Michael Saul, Petra Majdak, Samuel Perez, Matthew Reilly, Theodore Garland, Justin S Rhodes
Though exercise is critical for health, many lack the motivation to exercise, and it is unclear how motivation might be increased. To uncover the molecular underpinnings of increased motivation for exercise, we analyzed the transcriptome of the striatum in four mouse lines selectively bred for high voluntary wheel running and four non-selected control lines. The striatum was dissected and RNA was extracted and sequenced from four individuals of each line. We found multiple genes and gene systems with strong relationships to both selection and running history over the previous 6 days...
October 17, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27748566/mu-and-delta-opioid-receptor-knockout-mice-show-increased-colonic-sensitivity
#20
D Reiss, R A Ceredig, T Secher, J Boué, F Barreau, G Dietrich, C Gavériaux-Ruff
BACKGROUND: Opiates act through opioid receptors to diminish pain. Here, we investigated whether mu (MOR) and delta (DOR) receptor endogenous activity assessed in the whole mouse body or in particular at peripheral receptors on primary nociceptive neurons, control colonic pain. METHODS: We compared global MOR and DOR receptor knockout (KO) mice, mice with a conditional deletion of MOR and DOR in Nav1.8-positive nociceptive primary afferent neurons (cKO), and control floxed mice of both genders for visceral sensitivity...
October 17, 2016: European Journal of Pain: EJP
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