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https://www.readbyqxmd.com/read/28919445/cognitive-effects-of-labeled-addictolytic-medications
#1
REVIEW
Camille Noélie Pujol, Cecilia Paasche, Vincent Laprevote, Benoit Trojak, Pierre Vidailhet, Elisabeth Bacon, Laurence Lalanne
INTRODUCTION: Alcohol, tobacco, and illegal drug usage is pervasive throughout the world, and abuse of these substances is a major contributor to the global disease burden. Many pharmacotherapies have been developed over the last 50years to target addictive disorders. While the efficacy of these pharmacotherapies is largely recognized, their cognitive impact is less known. However, all substance abuse disorders are known to promote cognitive disorders like executive dysfunction and memory impairment...
September 14, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28918668/current-status-and-future-prospects-for-the-development-of-substance-abuse-vaccines
#2
Thomas R Kosten, Daryl Shorter, David Heekin
Substance use disorders (SUD) are a significant threat to both individual and public health. To date, SUD pharmacotherapy has focused primarily on agonist medications (i.e., nicotine replacement therapy for tobacco use disorder; methadone and buprenorphine for opioid use disorder), antagonist medications (i.e., naltrexone for opioid use disorder), and aversive therapy (i.e., disulfiram for alcohol use disorder). Pharmacotherapeutic approaches utilizing an immunological framework for medication development represent an important focus of study for treatment of these illnesses...
September 18, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28887129/disulfiram-is-a-slow-binding-partial-noncompetitive-inhibitor-of-20s-proteasome-activity
#3
Brian B Hasinoff, Daywin Patel
The alcohol abuse drug disulfiram has also been shown to exhibit potent cell growth inhibitory and anticancer activity. While a number of cellular and animal studies have suggested that disulfiram exhibits its anticancer activity through interaction with the proteasome, direct evidence for inhibition of proteasome activity is lacking. In this study we show that disulfiram potently inhibits the chymotrypsin-like activity of purified human 20S proteasome at low micromolar pharmacological concentrations. The enzyme progress curves displayed characteristics of a slow-binding reaction, similar to that observed for the FDA-approved proteasomal-targeted anticancer drugs bortezomib and carfilzomib...
September 5, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28875004/a-comparative-cytotoxic-evaluation-of-disulfiram-encapsulated-plga-nanoparticles-on-mcf-7-cells
#4
Hamidreza Fasehee, Ardeshir Ghavamzadeh, Kamran Alimoghaddam, Seyed-Hamidollah Ghaffari, Shahab Faghihi
Background: Disulfiram is oral aldehyde dehydrogenase (ALDH) inhibitor that has been used in the treatment of alcoholism. Recent studies show that this drug has anticancer properties; however, its rapid degradation has limited its clinical application. Encapsulation of disulfiram polymeric nanoparticles (NPs) may improve its anticancer activities and protect rapid degradation of the drug. Materials andMethods: A poly (lactide-co-Glycolide) (PLGA) was developed for encapsulation of disulfiram and its delivery into breast cancer cells...
April 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/28864067/a-novel-chemoradiation-targeting-stem-and-nonstem-pancreatic-cancer-cells-by-repurposing-disulfiram
#5
Juan Cong, Yangyang Wang, Xiao Zhang, Nan Zhang, Ling Liu, Klara Soukup, Theodoros Michelakos, Theodore Hong, Albert DeLeo, Lei Cai, Francesco Sabbatino, Soldano Ferrone, Hang Lee, Vera Levina, Bryan Fuchs, Kenneth Tanabe, Keith Lillemoe, Cristina Ferrone, Xinhui Wang
Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate of 6% and is projected to be the second leading cause of cancer death by 2030, underscoring the urgency to develop new strategies to improve current therapeutic modalities for PDAC. Targeting pancreatic cancer stem cells (PCSCs), which are resistant to radiation and chemotherapy, is a promising strategy. A novel approach which can be readily clinically translated is to repurpose disulfiram (DSF), a drug for treating alcoholism, to target PCSCs...
August 30, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28827047/high-drinking-in-the-dark-hdid-mice-are-sensitive-to-the-effects-of-some-clinically-relevant-drugs-to-reduce-binge-like-drinking
#6
John C Crabbe, Angela R Ozburn, Pamela Metten, Amanda Barkley-Levenson, Jason P Schlumbohm, Stephanie E Spence, Wyatt R Hack, Lawrence C Huang
BACKGROUND: There is a serious public health need for better understanding of alcohol use disorder disease mechanisms and for improved treatments. At this writing, only three drugs are approved by the Food and Drug Administration as medications to treat alcohol use disorders - disulfiram, naltrexone, and acamprosate. Binge drinking is a form of abusive alcohol drinking defined by the NIAAA as a drinking to blood alcohol levels (BALs)>0.08% during a period of approximately 2h. To model genetic risk for binge-like drinking, we have used selective breeding to create a unique animal model, High Drinking in the Dark (HDID) mice...
September 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28811616/synthesis-free-pet-imaging-of-brown-adipose-tissue-and-tspo-via-combination-of-disulfiram-and-64-cucl2
#7
Jing Yang, Jian Yang, Lu Wang, Anna Moore, Steven H Liang, Chongzhao Ran
PET imaging is a widely applicable but a very expensive technology. On-site synthesis is one important contributor to the high cost. In this report, we demonstrated the feasibility of a synthesis-free method for PET imaging of brown adipose tissue (BAT) and translocator protein 18 kDa (TSPO) via a combination of disulfiram, an FDA approved drug for alcoholism, and (64)CuCl2 (termed (64)Cu-Dis). In this method, a step-wise injection protocol of (64)CuCl2 and disulfiram was used to accomplish the purpose of synthesis-free...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28768860/zinc-finger-containing-cellular-transcription-corepressor-zbtb25-promotes-influenza-virus-rna-transcription-and-is-a-target-for-zinc-ejector-drugs
#8
Shu-Chuan Chen, King-Song Jeng, Michael M C Lai
Influenza A virus (IAV) replication relies on an intricate interaction between virus and host cells. How the cellular proteins are usurped for IAV replication remains largely obscure. The aim of this study was to search for novel and potential cellular factors that participate in IAV replication. ZBTB25, a transcription repressor of a variety of cellular genes, was identified by an RNAi genomic library screening. Depletion of ZBTB25 significantly reduced IAV production. Conversely, overexpression of ZBTB25 enhanced it...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28753074/acute-pneumonitis-associated-with-nickel-carbonyl-exposure-in-the-workplace
#9
Nena Bowman, E Martin Caravati, B Z Horowitz, Barbara Insley Crouch
BACKGROUND: We describe the clinical course of one industrial technician occupationally exposed to nickel carbonyl (NiC). CASE REPORT: A 50-year-old male industrial technician presented with complaints of nausea, myalgia, and cough to a local clinic after suspected occupational exposure to nickel carbonyl. He has no history of lung disease or smoking. His initial urine nickel concentration was 692 ug/L. He had infiltrates on the initial chest X-ray (CXR) and an oxygen saturation (O2) of 97% on room air...
July 28, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28729482/brca1-and-brca2-tumor-suppressors-protect-against-endogenous-acetaldehyde-toxicity
#10
Eliana Mc Tacconi, Xianning Lai, Cecilia Folio, Manuela Porru, Gijs Zonderland, Sophie Badie, Johanna Michl, Irene Sechi, Mélanie Rogier, Verónica Matía García, Ankita Sati Batra, Oscar M Rueda, Peter Bouwman, Jos Jonkers, Anderson Ryan, Bernardo Reina-San-Martin, Joannie Hui, Nelson Tang, Alejandra Bruna, Annamaria Biroccio, Madalena Tarsounas
Maintenance of genome integrity requires the functional interplay between Fanconi anemia (FA) and homologous recombination (HR) repair pathways. Endogenous acetaldehyde, a product of cellular metabolism, is a potent source of DNA damage, particularly toxic to cells and mice lacking the FA protein FANCD2. Here, we investigate whether HR-compromised cells are sensitive to acetaldehyde, similarly to FANCD2-deficient cells. We demonstrate that inactivation of HR factors BRCA1, BRCA2, or RAD51 hypersensitizes cells to acetaldehyde treatment, in spite of the FA pathway being functional...
July 20, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28728114/variation-in-receipt-of-pharmacotherapy-for-alcohol-use-disorders-across-racial-ethnic-groups-a-national-study-in-the-u-s-veterans-health-administration
#11
Emily C Williams, Shalini Gupta, Anna D Rubinsky, Joseph E Glass, Rhonda Jones-Webb, Kara M Bensley, Alex H S Harris
OBJECTIVE: Pharmacologic treatment is recommended for alcohol use disorders (AUD), but most patients do not receive it. Although racial/ethnic minorities have greater AUD consequences than whites, whether AUD medication receipt varies across race/ethnicity is unknown. We evaluate this in a national sample. METHODS: Electronic health records data were extracted for all black, Hispanic, and/or white patients who received care at the U.S. Veterans Health Administration (VA) during Fiscal Year 2012 and had a documented AUD diagnosis...
July 11, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28714728/functional-neural-changes-following-behavioral-therapies-and-disulfiram-for-cocaine-dependence
#12
Elise E DeVito, Guangheng Dong, Hedy Kober, Jiansong Xu, Kathleen M Carroll, Marc N Potenza
A growing literature exists on neural correlates of treatment outcome. However, different types-or components of-treatment have distinct theorized mechanisms of action. And it is not yet known how changes in neural activity across treatment relate to engagement in different treatment components. Participants with cocaine use disorders in a randomized clinical trial received cognitive-behavioral therapy (CBT) plus, in a 2 × 2 design, contingency management (CM) or no CM, and disulfiram or placebo. Participants performed a functional MRI Stroop task, a measure of cognitive control, at the beginning of and after the 12-week treatment...
August 2017: Psychology of Addictive Behaviors: Journal of the Society of Psychologists in Addictive Behaviors
https://www.readbyqxmd.com/read/28709722/involvement-of-dopamine-beta-hydroxylase-in-the-neuroendocrine-immune-regulatory-network-of-white-shrimp-litopenaeus-vannamei
#13
Winton Cheng, Ya-Wen Ka, Chin-Chyuan Chang
In shrimp, the biosynthesis of catecholamines, including dopamine and norepinephrine, is required for physiological and immunological responses against stress. Dopamine beta-hydroxylase (DBH), a copper-containing monooxygenase enzyme that plays an important role in catecholamine synthesis of the neuroendocrine regulatory network, was identified in Litopenaeus vannamei. In the present study, the potential role of DBH in the immunocompetence of L. vannamei was further estimated by depleting DBH by pharmaceutical inhibition of disulfiram and a gene silencing technique of L...
July 11, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28674046/repurposing-thiram-and-disulfiram-as-antibacterial-agents-for-multidrug-resistant-staphylococcus-aureus-infections
#14
Timothy E Long
Thiram and disulfiram were evaluated as antibacterial agents against multidrug-resistant Staphylococcus aureus Against a 30-member panel comprised of vancomycin-susceptible, vancomycin-intermediate, and vancomycin-resistant S. aureus strains, the MIC90 values of the respective test agents were 4 and 16 μg/ml. Additional analyses revealed that thiram and disulfiram are rapid-acting bacteriostatic agents with narrow, Gram-positive-bacterium spectrum activity. Synergy studies further determined that disulfiram increases the vancomycin susceptibility of three clinical vancomycin-resistant S...
September 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28668395/gc-ms-based-metabolomics-of-csf-and-blood-serum-metabolic-phenotype-for-a-rat-model-of-cefoperazone-induced-disulfiram-like-reaction
#15
Linsheng Liu, Chenrong Huang, Yicong Bian, Liyan Miao
Cefoperazone is most popularly used in the treatment of complicated infections clinically. Concomitant ingestion of ethnaol and cefoperazone may cause a disulfiram-like reaction. However, very little is known about the possible interactions between cefoperazone treatment and an alcohol with regard to the induction of disulfiram-like reaction. Study of the metabolic impact of cotreatment with cefoperazone and alcohol on animals can facilitate the identification of markers relevant to disulfiram-like reaction...
August 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28658981/pharmacotherapy-of-alcoholism-an-update-on-approved-and-off-label-medications
#16
Michael Soyka, Christian A Müller
Only a few medications are available for the treatment of alcohol use disorders (AUDs). Areas covered: This paper discusses approved AUD medications, including the opioid antagonists naltrexone and nalmefene (the latter is licensed for reduction of alcohol consumption only), the putative glutamate receptor antagonist acamprosate and the aldehyde dehydrogenase inhibitor disulfiram. It also covers off-label medications of interest, including topiramate, gabapentin, ondansetron, varenicline, baclofen, sodium oxybate and antidepressants...
August 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28615941/development-and-optimization-of-an-injectable-formulation-of-copper-diethyldithiocarbamate-an-active-anticancer-agent
#17
Mohamed Wehbe, Malathi Anantha, Minghan Shi, Ada Wai-Yin Leung, Wieslawa H Dragowska, Léon Sanche, Marcel B Bally
Copper diethyldithiocarbamate (Cu(DDC)2) is the active anticancer agent generated when disulfiram (DSF) is provided in the presence of copper. To date, research directed toward repurposing DSF as an anticancer drug has focused on administration of DSF and copper in combination, efforts that have proven unsuccessful in clinical trials. This is likely due to the inability to form Cu(DDC)2 at relevant concentrations in regions of tumor growth. Little effort has been directed toward the development of Cu(DDC)2 because of the inherent aqueous insolubility of the complex...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28595020/tamoxifen-inhibits-mitochondrial-membrane-damage-caused-by-disulfiram
#18
Natalia Pavon, Mabel Buelna-Chontal, Francisco Correa, Belem Yoval-Sánchez, Javier Belmont, Luz Hernández-Esquivel, Jose S Rodríguez-Zavala, Edmundo Chavez
In this work, we studied the protective effect of tamoxifen on disulfiram-induced mitochondrial membrane insult. The results indicate that tamoxifen circumvents inner membrane leakiness manifested by Ca2+ release, mitochondrial swelling, and collapse of the transmembrane electric gradient. Furthermore, it was found that tamoxifen prevents the inactivation of the mitochondrial enzyme aconitase and detachment of cytochrome c from the inner membrane. Interestingly, tamoxifen also inhibited disulfiram-promoted generation of hydrogen peroxide...
June 8, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28528648/copper-and-antibiotics-discovery-modes-of-action-and-opportunities-for-medicinal-applications
#19
Alex G Dalecki, Cameron L Crawford, Frank Wolschendorf
Copper is a ubiquitous element in the environment as well as living organisms, with its redox capabilities and complexation potential making it indispensable for many cellular functions. However, these same properties can be highly detrimental to prokaryotes and eukaryotes when not properly controlled, damaging many biomolecules including DNA, lipids, and proteins. To restrict free copper concentrations, all bacteria have developed mechanisms of resistance, sequestering and effluxing labile copper to minimize its deleterious effects...
2017: Advances in Microbial Physiology
https://www.readbyqxmd.com/read/28527633/anthelmintic-activity-of-cytochrome-p450-inhibitors-miconazole-and-clotrimazole-in-vitro-effect-on-the-liver-fluke-opisthorchis-felineus
#20
Viatcheslav A Mordvinov, Alexander G Shilov, Maria Y Pakharukova
Discovery of drugs for the treatment of opisthorchiasis and schistosomiasis is a high priority. The basic metabolic cytochrome P450 (CYP) system in parasitic flatworms contains a single gene. CYP of the liver fluke Opisthorchis felineus, the causative agent of opisthorchiasis, is important for survival of the worm, so it may be a promising target for therapeutics against liver fluke infection. The aims of this study were: (i) to analyse in-vitro anthelmintic activity of various CYP inhibitors using standard motility and mortality assays against juvenile and adult O...
May 17, 2017: International Journal of Antimicrobial Agents
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