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Kaku Goto, Naoya Kato, Raymond T Chung
We recently described that the anti-apoptotic AMPK-related kinase, SNARK, promotes transforming growth factor (TGF)-β signaling in hepatocellular carcinoma (HCC) cells, as a potentially new therapeutic target. Here we explored FDA-approved drugs inhibiting the enzymatic activity of SNARK, using an in vitro luminescence kinase assay system. Interestingly, the long-used anti-alcoholism drug disulfiram (DSF), also known as Antabuse, emerged as the top hit. Enzymatic kinetics analyses revealed that DSF inhibited SNARK kinase activity in a noncompetitive manner to ATP or phosphosubstrates...
September 2, 2016: Oncotarget
Radim Vrzal, Zdenek Dvorak
In the recent years, a therapeutic potential of disulfiram (Antabuse) complex with copper, as an anticancer drug, was recognized towards several cancer cell lines. The proteasome was suggested as one of the cellular targets for this compound. As the therapeutic use of diethyldithiocarbamate-copper complex (CuET) is expected to increase, it is of great interest to know whether this compound may be the source of drug-drug interactions via the induction of biotransformation enzymes, especially cytochromes P450 (CYPs)...
December 2016: Fundamental & Clinical Pharmacology
Ole Andersen, Jan Aaseth
Most acute and chronic human metal poisonings are due to oral or inhalation exposure. Almost 80% of published animal experiments on chelation in metal poisoning used single or repeated intraperitoneal, intramuscular or intravenous administration of metal and chelator, impeding extrapolation to clinical settings. Intramuscular administration of dimercaptopropanol (BAL) has until now been used in acute arsenic, lead, and mercury poisonings, but repeated BAL administration increased the brain uptake of As, Pb and Hg in experimental animals...
December 2016: Journal of Trace Elements in Medicine and Biology
Benjamin Rolland, François Paille, Claudine Gillet, Alain Rigaud, Romain Moirand, Corine Dano, Maurice Dematteis, Karl Mann, Henri-Jean Aubin
BACKGROUND: The latest French good practice recommendations (GPRs) for the screening, prevention, and treatment of alcohol misuse were recently published in partnership with the European Federation of Addiction Societies (EUFAS). This article aims to synthesize the GPRs focused on the pharmacotherapy of alcohol dependence. METHODS: A four-member European steering committee defined the questions that were addressed to an 18-member multiprofessional working group (WG)...
January 2016: CNS Neuroscience & Therapeutics
Vikas Sharma, Vikas Verma, Nand Lal, Santosh K Yadav, Saumya Sarkar, Dhanaraju Mandalapu, Konica Porwal, Tara Rawat, J P Maikhuri, Singh Rajender, V L Sharma, Gopal Gupta
Estrogen Receptor-β (ER-β), a tumor-suppressor in prostate cancer, is epigenetically repressed by hypermethylation of its promoter. DNA-methyltransferases (DNMTs), which catalyze the transfer of methyl-groups to CpG islands of gene promoters, are overactive in cancers and can be inhibited by DNMT-inhibitors to re-express the tumor suppressors. The FDA-approved nucleoside DNMT-inhibitors like 5-Azacytidine and 5-Aza-deoxycytidine carry notable concerns due to their off-target toxicity, therefore non-nucleoside DNMT inhibitors are desirable for prolonged epigenetic therapy...
November 2016: Molecular Carcinogenesis
Henning Gr Ønbæk, Mette Borre
INTRODUCTION: Cinnamon contains cumarin, which may be toxic to the liver. EU-regulations standardardize the amount of cinnamon in pastry including cinnamon rolls. The aim of the study was to investigate if cinnamon intake from pastry was associated with toxic or alcoholic hepatitis. RESULTS: We registered 58 patients with toxic hepatitis, 38 (66%) women and 20 (34%) men with a median age of 51 (range: 32-80) and 53 (range: 18-78) years, respectively. A total of 22 patients had primarily cholestasis and 36 had hepatitis biochemically...
December 8, 2014: Ugeskrift for Laeger
Hilde Fjeld, Guttorm Raknes
BACKGROUND: It is common practice to warn against intake of alcohol (ethanol) when taking metronidazole because of the risk of an effect similar to disulfiram (Antabuse). In this article we investigate whether such a warning has any real basis. KNOWLEDGE BASE: The article is based on a review of relevant literature retrieved through a search in PubMed. A search was also made in the WHO's database on adverse effects. RESULTS: No in-vitro studies, animal models, reports of adverse effects or clinical studies provide any convincing evidence of a disulfiram-like interaction between ethanol and metronidazole...
September 16, 2014: Tidsskrift for Den Norske Lægeforening: Tidsskrift for Praktisk Medicin, Ny Række
No abstract text is available yet for this article.
1958: Biological Sciences
(no author information available yet)
No abstract text is available yet for this article.
April 1955: International Journal on Alcohol and Alcoholism
No abstract text is available yet for this article.
1950: Acta Pharmacologica et Toxicologica
C A Cahill
A community program for effective control of alcoholism utilizing obligatory administration of disulfiram (Antabuse) is described. The results over a three-and-one-half-year study period are a reduced rate of rehospitalization, shorter duration of hospitalization in the event of readmission, and reduced morbidity.
September 1967: Community Mental Health Journal
Richard D Dinnen, Yuehua Mao, Wanglong Qiu, Nicholas Cassai, Vesna N Slavkovich, Gwen Nichols, Gloria H Su, Paul Brandt-Rauf, Robert L Fine
Pancreatic cancer cell lines with mutated ras underwent an alternative form of cell death (aponecrosis) when treated concomitantly with clinically achievable concentrations of arsenic trioxide, ascorbic acid, and disulfiram (Antabuse; AAA). AAA's major effects are mediated through generation of intracellular reactive oxygen species (ROS) and more than 50% decline in intracellular ATP. N-acetyl cysteine and a superoxide dismutase mimetic prevented aponecrosis and restored intracellular ATP levels. DIDS (4,4'-diisothiocyanatostilbene-2, 2' disulfonic acid), the pan- Voltage-Dependent Anion Channel (VDAC), -1, 2, 3 inhibitor and short hairpin RNA (shRNA) to VDAC-1 blocked cell death and ROS accumulation...
December 2013: Molecular Cancer Therapeutics
Jarmila Navrátilová, Tereza Hankeová, Petr Beneš, Jan Šmarda
BACKGROUND: Resistance of cancer cells to chemotherapeutic agents is a major cause of treatment failure in patients with cancer. The drug resistance of tumor cells can be significantly modified by specific features of tumor microenvironment, such as oxygen depletion (hypoxia), glucose/energy deprivation and acidosis. METHODS: The effects of acidic tumor-like microenvironment on cytotoxicity of antabuse (disulfiram, DSF)/Cu(2+) complexes to MCF-7 breast carcinoma and HT-29 colon carcinoma cells were studied...
2013: Chemotherapy
Alessandra T Peana, Elio Acquas
Since Chevens' report, in the early 50's that his patients under treatment with the aldehyde dehydrogenase inhibitor, antabuse, could experience beneficial effects when drinking small volumes of alcoholic beverages, the role of acetaldehyde (ACD) in the effects of ethanol has been thoroughly investigated on pre-clinical grounds. Thus, after more than 25 years of intense research, a large number of studies have been published on the motivational properties of ACD itself as well as on the role that ethanol-derived ACD plays in the effects of ethanol...
2013: Frontiers in Behavioral Neuroscience
Gro Askgaard, Søren Friis, Jesper Hallas, Lau C Thygesen, Anton Pottegård
Experimental studies have indicated that disulfiram (Antabuse) has antineoplastic effects against melanoma, breast, and prostate cancer. To explore this hypothesis, we examined the association between disulfiram use and these cancers in a nationwide register-based case-control study nested within ever-users (≥one prescription) of disulfiram. Cases were all Danish individuals with a histologically verified first-time diagnosis of malignant melanoma, breast, or prostate cancer during 2000-2009. For each case, we selected four cancer-free controls matched for age, sex, and year of first disulfiram prescription using risk set sampling...
May 2014: European Journal of Cancer Prevention
Henrik Thiesen
No abstract text is available yet for this article.
July 2013: Drug and Alcohol Review
Suchitra Krishnan-Sarin, Stephanie O'Malley, John H Krystal
Developing pharmacotherapies to treat alcohol dependence and associated health problems traditionally has been based on gaining a better understanding of the neuroscience underlying alcohol-drinking behavior. To date, three medications have been approved for the treatment of alcohol dependence: disulfiram (Antabuse®), naltrexone (Revia®, Vivitrol®, and Naltrel®), and acamprosate (Campral®). However, these medications have modest efficacy, and there is a great need for newer medications that target different neurochemical systems and which could be used either as adjunctive treatments or to treat subpopulations of drinkers...
2008: Alcohol Research & Health: the Journal of the National Institute on Alcohol Abuse and Alcoholism
Meriem Gaval-Cruz, Larry Cameron Liles, Paul Michael Iuvone, David Weinshenker
The anti-alcoholism medication, disulfiram (Antabuse), decreases cocaine use in humans regardless of concurrent alcohol consumption and facilitates cocaine sensitization in rats, but the functional targets are unknown. Disulfiram inhibits dopamine β-hydroxylase (DBH), the enzyme that converts dopamine (DA) to norepinephrine (NE) in noradrenergic neurons. The goal of this study was to test the effects of chronic genetic or pharmacological DBH inhibition on behavioral responses to cocaine using DBH knockout (Dbh -/-) mice, disulfiram, and the selective DBH inhibitor, nepicastat...
2012: PloS One
Pete M Ellis, Alan T Dronsfield
Seventy-five years after its first medical use was described, disulfiram's place in treatment is being favourably re-evaluated. This paper reviews its discovery and subsequent development.
July 2013: Drug and Alcohol Review
Graeme Hogarth
Dithiocarbamates are highly versatile mono-anionic chelating ligands which form stable complexes with all the transition elements and also the majority of main group, lanthanide and actinide elements. They are easily prepared from primary or secondary amines and depending upon the nature of the cation can show good solubility in water or organic solvents. They are related to the thiuram disulfides by a one-electron redox process (followed by dimerisation via sulfur-sulfur bond formation) which is easily carried out upon addition of iodide or ferric salts...
October 2012: Mini Reviews in Medicinal Chemistry
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