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https://www.readbyqxmd.com/read/28729482/brca1-and-brca2-tumor-suppressors-protect-against-endogenous-acetaldehyde-toxicity
#1
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
#2
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
#3
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...
July 17, 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
#4
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-multi-drug-resistant-staphylococcus-aureus-infections
#5
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 (VSSA), vancomycin-intermediate (VISA) and vancomycin-resistant (VRSA) 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 bacteria spectrum activity. Synergy studies further determined that disulfiram increases the vancomycin susceptibility of three clinical VRSA strains in vitro, thus establishing a potential use in combination therapy...
July 3, 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
#6
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...
June 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28658981/pharmacotherapy-of-alcoholism-an-update-on-approved-and-off-label-medications
#7
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...
July 24, 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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28518151/disulfiram-copper-selectively-eradicates-aml-leukemia-stem-cells-in-vitro-and-in-vivo-by-simultaneous-induction-of-ros-jnk-and-inhibition-of-nf-%C3%AE%C2%BAb-and-nrf2
#12
Bing Xu, Shiyun Wang, Rongwei Li, Kai Chen, Lingli He, Manman Deng, Vinodh Kannappan, Jie Zha, Huijuan Dong, Weiguang Wang
Acute myeloid leukemia (AML) is a heterogeneous malignancy. Despite the advances in past decades, the clinical outcomes of AML patients remain poor. Leukemia stem cells (LSCs) is the major cause of the recurrence of AML even after aggressive treatment making, promoting development of LSC-targeted agents is an urgent clinical need. Although the antitumor activity of disulfiram (DS), an approved anti-alcoholism drug, has been demonstrated in multiple types of tumors including hematological malignancies such as AML, it remains unknown whether this agent would also be able to target cancer stem cells like LSCs...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28490767/biliverdin-reductase-inhibitors-did-not-improve-severe-unconjugated-hyperbilirubinemia-in-vivo
#13
Remco van Dijk, Sem J Aronson, Dirk R de Waart, Stan F van de Graaf, Suzanne Duijst, Jurgen Seppen, Ronald Oude Elferink, Ulrich Beuers, Piter J Bosma
We aimed to identify potent biliverdin reductase (BVRA) inhibitors as a novel concept for the treatment of severe unconjugated hyperbilirubinemia. 1280 FDA-approved compounds were screened in vitro for their ability to inhibit human and rat BVRA activity and 26 compounds were identified as BVRA inhibitors. Montelukast and Disulfiram were selected as potentially clinically applicable drugs and tested to reduce serum unconjugated bilirubin (UCB) levels in the Ugt1a1-deficient rat, a model for chronic unconjugated hyperbilirubinemia...
May 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28465838/a-critical-review-of-the-evidence-concerning-the-hiv-latency-reversing-effect-of-disulfiram-the-possible-explanations-for-its-inability-to-reduce-the-size-of-the-latent-reservoir-in-vivo-and-the-caveats-associated-with-its-use-in-practice
#14
REVIEW
Harry D J Knights
Combination antiretroviral therapy (cART) effectively suppresses the replication of human immunodeficiency virus type 1 (HIV-1), improves immune function, and decreases the morbidity of acquired immune deficiency syndrome (AIDS). However, it is unable to eradicate the virus because it does not eliminate latently infected cells. The latent reservoir poses the major barrier to an HIV-1 cure. The "shock and kill" strategy aims to reactivate the virus and destroy latently infected cells. Many latency reversing agents (LRAs) reactivate HIV in vitro, but the absence of damaging side-effects and efficacy in vivo make disulfiram particularly promising...
2017: AIDS Research and Treatment
https://www.readbyqxmd.com/read/28460441/inflammatory-breast-cancer-tumor-emboli-express-high-levels-of-anti-apoptotic-proteins-use-of-a-quantitative-high-content-and-high-throughput-3d-ibc-spheroid-assay-to-identify-targeting-strategies
#15
Jay Arora, Scott J Sauer, Michael Tarpley, Peter Vermeulen, Charlotte Rypens, Steven Van Laere, Kevin P Williams, Gayathri R Devi, Mark W Dewhirst
Inflammatory breast cancer (IBC) is one of the most lethal breast cancer variants; with existing therapy, 5-yr survival rate is only 35%. Current barriers to successful treatment of IBC include frequent infiltration and the presence of tumor cell clusters, termed tumor emboli, within the breast parenchyma and lymphatics. Prior studies have identified the role of anti-apoptotic signaling, in particular hyperactivation of NFκB and its target genes, in IBC pathobiology and therapeutic resistance. The objectives of this study were to: (1) determine if IBC tumor emboli express anti-apoptotic proteins and (2) develop a high content, multiparametric assay to assess the morphology of the IBC 3D spheroids and to optimize a high throughput format to screen for compounds that can inhibit the formation of the IBC tumor clusters/embolic structures...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28440205/in-vitro-collapsing-colon-cancer-cells-by-selectivity-of-disulfiram-loaded-charge-switchable-nanoparticles-against-cancer-stem-cells
#16
Marwa Muhammad Abu-Serie, Fatma Hassan El-Rashidy
BACKGROUND: Different strategies against colon cancer are accompanied by treatment failure, because of drug toxicity toward normal cells and cancer stem cells (CSCs) resistance. However, previous patent evaluated liposome that encapsulated inhibitor of CSCs' aldehyde dehydrogenase (ALDH)1; disulfiram, for targeting breast CSCs. Liposome has disadvantages due to its hydrophobicity. OBJECTIVES: Designing hydrophilic nanoparticles have selectivity to release disulfiram in CC cells rather than in normal colonocytes based on variation in microenvironment between normal and cancer cells...
April 24, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/28406579/disparities-in-pharmacotherapy-for-alcohol-use-disorder-in-the-context-of-universal-health-care-a-swedish-register-study
#17
Katherine J Karriker-Jaffe, Jianguang Ji, Jan Sundquist, Kenneth S Kendler, Kristina Sundquist
BACKGROUND AND AIMS: Pharmacotherapy can be an important part of the continuum of care for alcohol use disorder (AUD). The Swedish universal health-care system emphasizes provision of care to marginalized groups. The primary aim was to test associations of neighborhood deprivation and disadvantaged social status with receipt of AUD pharmacotherapy in this context. DESIGN: Data from linked population registers were used to follow an open cohort over 7 years. SETTING: Sweden...
August 2017: Addiction
https://www.readbyqxmd.com/read/28373070/disulfiram-suppresses-cancer-stem-like-properties-and-stat3-signaling-in-triple-negative-breast-cancer-cells
#18
Yoon-Jae Kim, Ji Young Kim, Nahyun Lee, Eunhye Oh, Daeil Sung, Tae-Min Cho, Jae Hong Seo
In the presence of copper (Cu), disulfiram (DSF) suppresses properties associated with cancer stem cells (CSCs) in breast cancer, but the mechanism of action is poorly understood. In the present study, we observed that DSF/Cu treatment induced apoptosis, mediated by caspase-3 activation in triple-negative breast cancer (TNBC) cells. DSF/Cu treatment also specifically targeted CSC-like cell populations, marked by the inhibition of ALDH1 activity, the suppression of CD44+/CD24-and CD49f+/CD24 + subpopulations, and the subsequent impairment of mammosphere formation...
May 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28344087/subacute-alcohol-and-or-disulfiram-intake-affects-bioelements-and-redox-status-in-rat-testes
#19
Ana Djuric, Aida Begic, Borko Gobeljic, Ana Pantelic, Goran Zebic, Ivana Stevanovic, Dragan Djurdjevic, Milica Ninkovic, Vera Prokic, Ivan Stanojevic, Danilo Vojvodic, Mirjana Djukic
The aim of the study was to investigate if alcohol and disulfiram (DSF) individually and in combination affect bioelements' and red-ox homeostasis in testes of the exposed rats. The animals were divided into groups according to the duration of treatments (21 and/or 42 days): C21/C42 groups (controls); OL21 and OL22-42 groups (0.5 mL olive oil intake); A1-21 groups (3 mL 20% ethanol intake); DSF1-21 groups (178.5 mg DSF/kg/day intake); and A21+DSF22-42 groups (the DSF ingestion followed previous 21 days' treatment with alcohol)...
March 24, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28340172/repositioning-disulfiram-as-a-radiosensitizer-against-atypical-teratoid-rhabdoid-tumor
#20
Young Eun Lee, Seung Ah Choi, Pil Ae Kwack, Hak Jae Kim, Il Han Kim, Kyu-Chang Wang, Ji Hoon Phi, Ji Yeoun Lee, Sangjoon Chong, Sung-Hye Park, Kyung Duk Park, Do Won Hwang, Kyeung Min Joo, Seung-Ki Kim
Background.: Atypical teratoid/rhabdoid tumor (AT/RT) is one of the most common malignant brain tumors in infants. Although cancer stem cells of AT/RT express aldehyde dehydrogenase (ALDH), effective chemotherapies against AT/RT have not been established. Here, we examined radiosensitizing effects of disulfiram (DSF), an irreversible inhibitor of ALDH against AT/RT for a novel therapeutic method. Methods.: Patient-derived primary cultured AT/RT cells (SNU.AT/RT-5 and SNU...
March 17, 2017: Neuro-oncology
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