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https://www.readbyqxmd.com/read/28730160/epigenetic-interactions-between-alcohol-and-cannabinergic-effects-focus-on-histone-modification-and-dna-methylation
#1
Tiyash Parira, Alejandra Laverde, Marisela Agudelo
Epigenetic studies have led to a more profound understanding of the mechanisms involved in chronic conditions. In the case of alcohol addiction, according to the National Institute on Alcohol Abuse and Alcoholism, 16 million adults suffer from Alcohol Use Disorders (AUDs). Even though therapeutic interventions like behavioral therapy and medications to prevent relapse are currently available, no robust cure exists, which stems from the lack of understanding the mechanisms of action of alcohol and the lack of development of precision medicine approaches to treat AUDs...
April 2017: Journal of Alcoholism and Drug Dependence
https://www.readbyqxmd.com/read/28666811/%C3%AE-6%C3%AE-2-subunit-containing-nicotinic-acetylcholine-receptors-exert-opposing-actions-on-rapid-dopamine-signaling-in-the-nucleus-accumbens-of-rats-with-high-versus-low-response-to-novelty
#2
Cody A Siciliano, J Michael McIntosh, Sara R Jones, Mark J Ferris
Determining neurobiological factors that contribute to individual variance in drug addiction vulnerability allows for identification of at-risk populations, use of preventative measures and personalized medicine in the treatment of substance use disorders. Rodents that exhibit high locomotor activity when exploring an inescapable novel environment (high-responder; HR) are more susceptible to the reinforcing effects of many abused compounds, including nicotine, as compared to animals that exhibit low locomotor activity (low-responder; LR)...
June 27, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28663570/brain-stimulation-in-obesity
#3
REVIEW
C H Göbel, V M Tronnier, T F Münte
Obesity is taking up epidemic proportions worldwide with significant impacts on the health of both the affected individual and on society as a whole. Treatment approaches consist of behavioural and pharmacological approaches, however these are often found to be ineffective. In severe obesity, bariatric surgery is frequently performed. Unfortunately, 40% of patients show substantial weight gain over the long-term or display the associated metabolic syndrome, making the development of novel therapies necessary...
June 30, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28645915/cebranopadol-blocks-the-escalation-of-cocaine-intake-and-conditioned-reinstatement-of-cocaine-seeking-in-rats
#4
Giordano de Guglielmo, Alessandra Matzeu, Jenni Kononoff, Julia Mattioni, Remi Martin-Fardon, Olivier George
Cebranopadol is a novel agonist of nociceptin/orphanin FQ peptide (NOP) and opioid receptors with analgesic properties that is being evaluated in clinical Phase 2 and Phase 3 trials for the treatment of chronic and acute pain. Recent evidence indicates that the combination of opioid and NOP receptor agonism may be a new treatment strategy for cocaine addiction. We sought to extend these findings by examining the effects of cebranopadol on cocaine self-administration (0.5 mg/kg/infusion) and cocaine conditioned reinstatement in rats with extended access to cocaine...
June 23, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28645606/presence-of-a-malignant-tumor-as-a-novel-predictive-factor-for-repeated-recurrences-of-chronic-subdural-hematoma
#5
Yusuke S Hori, Mizuho Aoi, Kazunori Oda, Toru Fukuhara
BACKGROUND: Various risk factors for recurrence of chronic subdural hematomas (CSDHs) have been reported, including alcohol addiction and diabetes mellitus. However, the significance of malignant tumors with respect to CSDH recurrence remains unclear. METHODS: We retrospectively evaluated 281 patients with a first-time CSDH from 2006 to 2016. The difference in the recurrence rate within 100 days postoperatively was compared between patients with a past or present extracranial malignant tumor and those with neither a past nor present extracranial malignant tumor at presentation...
June 20, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28640835/bilateral-blockade-of-mek-and-pi3k-mediated-pathways-downstream-of-mutant-kras-as-a-treatment-approach-for-peritoneal-mucinous-malignancies
#6
Murali R Kuracha, Peter Thomas, Brian W Loggie, Venkatesh Govindarajan
Mucinous colorectal adenocarcinomas (MCAs) are clinically and morphologically distinct from nonmucinous colorectal cancers (CRCs), show a distinct spectrum of genetic alterations (higher KRAS mutations, lower p53, high MUC2), exhibit more aggressive behavior (more prone to peritoneal dissemination and lymph node involvement) and are associated with poorer response to chemotherapy with limited treatment options. Here, we report the effectiveness of combinatorial targeting of two KRAS-mediated parallel pathways in reducing MUC2 production and mucinous tumor growth in vitro and in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28631421/impact-of-synthetic-cannabinoids-on-the-duration-of-opioid-related-withdrawal-and-craving-among-patients-of-addiction-clinics-in-kazakhstan-a-prospective-case-control-study
#7
Mariya Prilutskaya, Francesco Saverio Bersani, Ornella Corazza, Sergey Molchanov
OBJECTIVE: The aim of the study was to prospectively assess whether regular use of synthetic cannabinoids (SCs) affects the duration of opioid-related withdrawal and craving symptoms in patients undergoing drug detoxification treatments. METHODS: Patients (n = 193) with opioid use disorder, among which 47 patients are regularly using SCs, underwent integrated drug detoxification therapies. The Clinical Opiate Withdrawal Scale and a specific visual analogue scale were used to assess opioid withdrawal and craving symptoms over time...
May 2017: Human Psychopharmacology
https://www.readbyqxmd.com/read/28625446/a-novel-treatment-for-chronic-opioid-use-after-surgery
#8
Paul F White, Ofelia Loani Elvir-Lazo, Hector Hernandez
In a recent article from the Center for Disease Control, the authors addressed the current opioid epidemic in America and emphasized the importance of utilizing non-opioid analgesic alternatives to opioid medication for treating chronic pain. In cases where non-opioid analgesic drugs alone have failed to produce adequate pain relief, these authors suggested that non-pharmacologic therapies should also be considered. This Case Series describes a pilot study designed to evaluate a novel non-pharmacologic approach to treating long-standing (>1year) opioid dependency...
August 2017: Journal of Clinical Anesthesia
https://www.readbyqxmd.com/read/28624806/targeting-the-tumor-promoting-microenvironment-in-met-amplified-nsclc-cells-with-a-novel-inhibitor-of-pro-hgf-activation
#9
Benjamin Y Owusu, Shantasia Thomas, Phanindra Venukadasula, Zhenfu Han, James W Janetka, Robert A Galemmo, Lidija Klampfer
Targeted therapeutic agents, such as inhibitors of epithelial growth factor receptor (EGFR), have transformed the management of non-small cell lung cancer (NSCLC) patients. MET-amplified NSCLC cells display resistance to EGFR-targeting agents, but are addicted to MET signaling for survival and proliferation and are sensitive to MET inhibition. However, responsive cancer cells invariably develop resistance to MET-targeted treatment.The tumor microenvironment plays a major role in resistance to anticancer therapy...
May 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28618002/novel-psychoactive-substance-use-among-treatment-seeking-opiate-users-the-role-of-life-events-and-psychiatric-symptoms
#10
Máté Kapitány-Fövény, Judit Farkas, Patrícia Andrea Pataki, Anna Kiss, Janka Horváth, Róbert Urbán, Zsolt Demetrovics
OBJECTIVE: Over the past 5 years, a shift to the use of novel psychoactive substances (NPS) has been observed among opioid users. The aim of this study was to assess the potential reasons for NPS use among treatment-seeking patients receiving opiate substitution therapy. METHOD: A structured questionnaire was filled out by a sample of 198 opiate dependent patients of Hungary's National Institute of Psychiatry and Addiction. This questionnaire assessed demographics, treatment characteristics, lifetime substance use, potential reasons for NPS use, negative life events (Life Events Scale), and psychiatric symptoms (Brief Symptom Inventory)...
May 2017: Human Psychopharmacology
https://www.readbyqxmd.com/read/28572168/preclinical-efficacy-and-molecular-mechanism-of-targeting-cdk7-dependent-transcriptional-addiction-in-ovarian-cancer
#11
Zhenfeng Zhang, Huixin Peng, Xiaojie Wang, Xia Yin, Pengfei Ma, Ying Jing, Mei-Chun Cai, Jin Liu, Meiying Zhang, Shengzhe Zhang, Kaixuan Shi, Wei-Qiang Gao, Wen Di, Guanglei Zhuang
Ovarian cancer remains a significant cause of gynecological cancer mortality and novel therapeutic strategies are urgently needed in clinic as new treatment options. We previously showed that BET bromodomain inhibitors displayed promising efficacy for the treatment of epithelial ovarian cancer by downregulating pivot transcription factors. However, the potential anti-tumor activities and molecular mechanisms of other epigenetic or transcriptional therapies have not been systematically determined. Here, by performing an unbiased high-throughput drug screen to identify candidate compounds with antineoplastic effects, we identified THZ1, a recently developed covalent CDK7 inhibitor, as a new transcription-targeting compound that exerted broad cytotoxicity against ovarian tumors...
June 1, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28564576/the-endocannabinoid-system-as-a-target-for-addiction-treatment-trials-and-tribulations
#12
REVIEW
Matthew E Sloan, Joshua L Gowin, Vijay A Ramchandani, Yasmin L Hurd, Bernard Le Foll
Addiction remains a major public health concern, and while pharmacotherapies can be effective, clinicians are limited by the paucity of existing interventions. Endocannabinoid signaling is involved in reward and addiction, which raises the possibility that drugs targeting this system could be used to treat substance use disorders. This review discusses findings from randomized controlled trials evaluating cannabinergic medications for addiction. Current evidence suggests that pharmacotherapies containing delta-9-tetrahydrocannabinol, such as dronabinol and nabiximols, are effective for cannabis withdrawal...
May 28, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28553834/evidence-for-a-long-lasting-compulsive-alcohol-seeking-phenotype-in-rats
#13
Chiara Giuliano, Yolanda Peña-Oliver, Charles R Goodlett, Rudolf N Cardinal, Trevor W Robbins, Edward T Bullmore, David Belin, Barry J Everitt
Excessive drinking to intoxication is the major behavioral characteristic of those addicted to alcohol but it is not the only one. Indeed, those addicted to alcohol also crave alcoholic beverages and spend time and put much effort into compulsively seeking alcohol, before eventually drinking large amounts. Unlike this excessive drinking, for which treatments exist, compulsive alcohol seeking is therefore another key feature of the persistence of alcohol addiction since it leads to relapse and for which there are few effective treatments...
May 29, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28552458/opioid-addiction-who-are-your-real-friends
#14
REVIEW
Shoshana Eitan, Michael A Emery, M L Shawn Bates, Christopher Horrax
Opioid addiction is a chronic and relapsing mental health disorder. However, only some individuals exposed to opioids, either recreationally or during the course of pain management, will develop addiction. The reasons why some individuals develop addiction and some are spared are not fully understood. Studies indicate that it is likely a combination of genetic predispositions and environmental conditions. Given the role of environmental factors in human addiction, this review examines the role of social environments and social interactions in the development of opioid addictive-like behaviors in rodent studies...
May 26, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28541119/treatment-of-opioid-use-disorder-with-ibogaine-detoxification-and-drug-use-outcomes
#15
Thomas Kingsley Brown, Kenneth Alper
BACKGROUND: Ibogaine is a monoterpene indole alkaloid used in medical and nonmedical settings for the treatment of opioid use disorder. Its mechanism of action is apparently novel. There are no published prospective studies of drug use outcomes with ibogaine. OBJECTIVES: To study outcomes following opioid detoxification with ibogaine. METHODS: In this observational study, 30 subjects with DSM-IV Opioid Dependence (25 males, 5 females) received a mean total dose of 1,540 ± 920 mg ibogaine HCl...
May 25, 2017: American Journal of Drug and Alcohol Abuse
https://www.readbyqxmd.com/read/28531265/utility-of-nonhuman-primates-in-substance-use-disorders-research
#16
Matthew L Banks, Paul W Czoty, Sidney S Negus
Substance use disorders (i.e., drug addiction) constitute a global and insidious public health issue. Preclinical biomedical research has been invaluable in elucidating the environmental, biological, and pharmacological determinants of drug abuse and in the process of developing innovative pharmacological and behavioral treatment strategies. For more than 70 years, nonhuman primates have been utilized as research subjects in biomedical research related to drug addiction. There are already several excellent published reviews highlighting species differences in both pharmacodynamics and pharmacokinetics between rodents and nonhuman primates in preclinical substance abuse research...
May 20, 2017: ILAR Journal
https://www.readbyqxmd.com/read/28523977/the-application-of-deep-brain-stimulation-in-the-treatment-of-psychiatric-disorders
#17
Ilse Graat, Martijn Figee, Damiaan Denys
Deep brain stimulation (DBS) is a last-resort treatment for neurological and psychiatric disorders that are refractory to standard treatment. Over the last decades, the progress of DBS in psychiatry has been slower than in neurology, in part owing to the heterogenic symptomatology and complex neuroanatomy of psychiatric disorders. However, for obsessive-compulsive disorder (OCD) DBS is now an accepted treatment. This study first reviews clinical outcomes and mechanisms of DBS for OCD, and then discusses these results in an overview of current and future psychiatric applications, including DBS for mood disorders, Tourette's syndrome, addiction, anorexia nervosa, autism, schizophrenia, and anxiety disorders...
April 2017: International Review of Psychiatry
https://www.readbyqxmd.com/read/28523558/epigenome-editing-in-the-brain
#18
Pavel Bashtrykov, Albert Jeltsch
Epigenome editing aims for an introduction or removal of chromatin marks at a defined genomic region using artificial EpiEffectors resulting in a modulation of the activity of the targeted functional DNA elements. Rationally designed EpiEffectors consist of a targeting DNA-binding module (such as a zinc finger protein, TAL effector, or CRISPR/Cas complex) and usually, but not exclusively, a catalytic domain of a chromatin-modifying enzyme. Epigenome editing opens a completely new strategy for basic research of the central nervous system and causal treatment of psychiatric and neurological diseases, because rewriting of epigenetic information can lead to the direct and durable control of the expression of disease-associated genes...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28521782/combining-alcohol-interventions-with-tobacco-addictions-treatment-in-primary-care-the-combat-study-a-pragmatic-cluster-randomized-trial
#19
Nadia Minian, Dolly Baliunas, Laurie Zawertailo, Aliya Noormohamed, Norman Giesbrecht, Christian S Hendershot, Bernard Le Foll, Jürgen Rehm, Andriy Samokhvalov, Peter L Selby
BACKGROUND: Tobacco and alcohol use present multiplicative risk for aerodigestive cancers. Reducing alcohol consumption improves smoking cessation outcomes and reduces cancer risk. Risky alcohol consumption and smoking are often treated separately despite concurrent treatment potentially leading to better outcomes for each. However, no rapidly scalable program exists for combined interventions in primary care clinics spread across wide geographic areas. This cluster randomized trial aims to report on the effects of a novel clinical decision support system (CDSS) on intervention rates by primary care practitioners addressing risky alcohol use in a smoking cessation program...
May 18, 2017: Implementation Science: IS
https://www.readbyqxmd.com/read/28516124/bioinformatic-analysis-for-profiling-drug-induced-chromatin-modification-landscapes-in-mouse-brain-using-chlp-seq-data
#20
Yong-Hwee Eddie Loh, Jian Feng, Eric Nestler, Li Shen
Chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq) is a powerful technology to profile genome-wide chromatin modification patterns and is increasingly being used to study the molecular mechanisms of brain diseases such as drug addiction. This protocol discusses the typical procedures involved in ChIP-seq data generation, bioinformatic analysis, and interpretation of results, using a chronic cocaine treatment study as a template. We describe an experimental design that induces significant chromatin modifications in mouse brain, and the use of ChIP-seq to derive novel information about the chromatin regulatory mechanisms involved...
February 5, 2017: Bio-protocol
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