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Benzbromarone

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https://www.readbyqxmd.com/read/28828541/role-of-the-oatp-transporter-family-and-a-benzbromarone-sensitiveefflux-transporter-in-the-hepatocellular-disposition-of-vincristine
#1
Johan Nicolaï, Louise Thevelin, Qi Bing, Bruno Stieger, Hugues Chanteux, Patrick Augustijns, Pieter Annaert
PURPOSE: Vincristine is known to interfere with OATP-mediated uptake of other compounds, hinting that vincristine itself could be a substrate of OATP transporters. The present study therefore aimed to investigate the role of OATP transporters in the hepatocellular disposition of vincristine. METHODS: Vincristine uptake was studied in suspended rat and human hepatocytes as well as OATP-transfected Chinese hamster ovary (CHO) cells in the absence and presence of OATP transporter inhibitors...
August 21, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28658988/updates-on-the-treatment-of-gout-including-a-review-of-updated-treatment-guidelines-and-use-of-small-molecule-therapies-for-difficult-to-treat-gout-and-gout-flares
#2
Rose Soskind, Daniel T Abazia, Mary Barna Bridgeman
Gout is a rheumatologic condition associated with elevated serum uric acid levels and deposition of monosodium urate crystals in joints and soft tissues. Areas covered: In this article, we describe the role of currently available drug therapies for managing acute gout flares and used in reducing serum urate levels. Further, we explore the role of novel small molecular therapies and biologic agents in the treatment of refractory or severe gout symptoms. A literature search of MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations Databases (1996-June 2017) was conducted utilizing the key words 'gout', 'interleukin-1 inhibitors', 'acute gout', 'gout treatment', 'urate lowering therapies', 'hyperuricemia', 'colchicine', 'pegloticase', 'lesinurad', 'xanthine oxidase', 'xanthine oxidase inhibitors', 'allopurinol', 'febuxostat', 'uricosurics', 'probenecid', and 'benzbromarone'...
August 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28598529/association-of-a-reactive-intermediate-derived-from-1-6-dihydroxy-metabolite-with-benzbromarone-induced-hepatotoxicity
#3
Mina Yoshida, Naoki Cho, Hidetaka Akita, Kaoru Kobayashi
Treatment with benzbromarone can be associated with liver injury, but the detailed mechanism remains unknown. Our recent studies demonstrated that benzbromarone was metabolized to 1',6-dihydroxybenzbromarone and followed by formation of reactive intermediates that were trapped by glutathione, suggesting that the reactive intermediates may be responsible for the liver injury. The aim of this study was to clarify whether the reactive intermediates derived from 1',6-dihydroxybenzbromarone is a risk factor of liver injury in mice...
June 9, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28544467/a-survey-on-the-beliefs-and-knowledge-of-gout-management-in-new-medical-graduates-new-south-wales-australia
#4
Matthew Terrill, John Riordan
AIM: To assess the beliefs and knowledge of gout management in new medical graduates. METHOD: A survey on gout management was sent to new medical graduates during their orientation week, New South Wales, Australia. RESULTS: Of 15 hospital networks, 11 agreed to participate. From these, 168 graduates responded (23.7% response rate). Most (81.1%) felt that gout was a serious disease, 51.2% answered that they had been taught adequately to manage acute gout, only 37...
May 25, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28539294/-effects-of-clostridium-butyricum-on-serum-uric-acid-and-inflammatory-mediators-in-rats-with-hyperuricemia
#5
Li Wang, Zhi-Rong Fang, Ya-Ting Shen, Yan-Bo Liu, Li-Li Liu
OBJECTIVE: To investigate the effects of intragastric administration of Clostridium butyricum in regulating serum uric acid, lipopolysaccharides (LPS), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in rats with hyperuricemia rats. METHODS: Forty SD rats were randomized into 4 equal groups, namely the normal control group, hyperuricemia model group, benzbromarone (3 mg/kg daily) intervention group and live Clostridium butyricum group (1.5×10(7) CFU/day)...
May 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28460508/-effect-of-febuxostat-on-epithelial-to-mesenchymal-transition-of-kidney-tubules-serum-interleukin-6-and-transforming-growth-factor-%C3%AE-1-in-hyperuricemic-rats
#6
Z M Lin, R S Zhang, C X Fan, Y L Liang, L Li, L Zhao, J C Qu, X Xu, H Y Zhao, X N Liu, K S Zhu
Objective: To observe the effect of febuxostat on epithelial-to-mesenchymal transition (EMT) of kidney tubules and the levels of serum IL-6 nad transforming growth factor (TGF)β(1) in hyperuricemic rats. Methods: Forty male SD rats were divided into 4 groups: normal control group (NC group), oteracil potassium group (OP group), oteracil potassium with febuxostat group (OF group) and oteracil potassium with benzbromarone group (OB group). Each group had 10 rats and balanced in body weights. To induce hyperuricemia, rats were given oteracil potassium by gastric gavage once a day for eight weeks...
May 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/28408375/uric-acid-is-associated-with-inflammatory-biomarkers-and-induces-inflammation-via-activating-the-nf-%C3%AE%C2%BAb-signaling-pathway-in-hepg2-cells
#7
Rosangela Spiga, Maria Adelaide Marini, Elettra Mancuso, Concetta Di Fatta, Anastasia Fuoco, Francesco Perticone, Francesco Andreozzi, Gaia Chiara Mannino, Giorgio Sesti
OBJECTIVE: Serum uric acid (UA) has been associated with increased risk of cardiovascular and metabolic diseases. However, the causal mechanisms linking elevated UA levels to cardio-metabolic diseases are still unsettled. One potential explanation for how UA might contribute to cardio-metabolic disease might be its ability to induce systemic inflammation. APPROACH AND RESULTS: Herein, we report a positive relationship between serum UA and acute-phase reactants, such as high-sensitivity C-reactive protein, fibrinogen, ferritin, complement C3, and erythrocyte sedimentation rate, in a cohort of 2731 nondiabetic adults...
June 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28386072/discovery-and-characterization-of-verinurad-a-potent-and-specific-inhibitor-of-urat1-for-the-treatment-of-hyperuricemia-and-gout
#8
Philip K Tan, Sha Liu, Esmir Gunic, Jeffrey N Miner
Gout is caused by elevated serum urate levels, which can be treated using inhibitors of the uric acid transporter, URAT1. Here, we characterize verinurad (RDEA3170), which is currently under evaluation for gout therapy. Verinurad specifically inhibits URAT1 with a potency of 25 nM. High affinity inhibition of uric acid transport requires URAT1 residues Cys-32, Ser-35, Phe-365 and Ile-481. Unlike other available uricosuric agents, the requirement for Cys-32 is unique to verinurad. Two of these residues, Ser-35 and Phe-365, are also important for urate transport kinetics...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28379501/cardiovascular-effects-of-urate-lowering-therapies-in-patients-with-chronic-gout-a-systematic-review-and-meta-analysis
#9
Tony Zhang, Janet E Pope
Objectives: To determine if urate-lowering treatment (ULT) in gout can reduce cardiovascular (CV) outcomes. Methods: Randomized trials were searched for treatment with ULT in gout. Eligible trials had to report CV safety of a ULT. Potential medications included allopurinol, febuxostat, pegloticase, rasburicase, probenecid, benzbromarone, sulphinpyrazone, losartan, fenofibrate and sodium-glucose linked transporter 2 inhibitors. Results: A total of 3084 citations were found, with 642 duplicates...
July 1, 2017: Rheumatology
https://www.readbyqxmd.com/read/28365572/cost-effectiveness-analysis-for-genotyping-before-allopurinol-treatment-to-prevent-severe-cutaneous-adverse-drug-reactions
#10
Ching-Hua Ke, Wen-Hung Chung, Yen-Hsia Wen, Yaw-Bin Huang, Hung-Yi Chuang, You-Lin Tain, Yu-Ching Lily Wang, Cheng-Chih Wu, Chien-Ning Hsu
OBJECTIVE: Patients with an HLA-B*58:01 allele have an increased risk of developing severe cutaneous adverse drug reactions (SCAR) when treated with allopurinol. Although one-off pharmacogenetic testing may prevent life-threatening adverse drug reactions, testing prior to allopurinol initiation incurs additional costs. The study objective was to evaluate the cost-effectiveness of HLA-B*58:01 screening compared with using other available urate-lowering agents (ULA). METHODS: A decision-analytical model was used to compare direct medical costs and effectiveness [including lifetime saved, quality-adjusted life-yrs (QALY) gained] in treating new patients with the following options: (1) genetic screening followed by allopurinol prescribing for noncarriers of HLAB* 58:01, (2) prescribing benzbromarone without screening, (3) prescribing febuxostat without screening, and (4) prescribing allopurinol without screening...
April 1, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28357121/uricosuric-targets-of-tranilast
#11
Asim K Mandal, Adriana Mercado, Andria Foster, Kambiz Zandi-Nejad, David B Mount
Uric acid, generated from the metabolism of purines, has both proven and emerging roles in human disease. Serum uric acid in humans is determined by production and by the net balance of reabsorption and secretion in kidney and intestine. In the human kidney, epithelial reabsorption dominates over secretion, such that in normal subjects there is at least 90% net reabsorption of filtered urate resulting in a fractional excretion of <10%. Tranilast, an anti-inflammatory drug with pleiotropic effects, has a marked hypouricemic, uricosuric effect in humans...
April 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28328020/detection-of-glutathione-conjugates-of-amiodarone-and-its-reactive-diquinone-metabolites-in-rat-bile-using-mass-spectrometry-tools
#12
Keyur R Parmar, Shalu Jhajra, Saranjit Singh
RATIONALE: Amiodarone is reported to cause hepato and pulmonary toxicity in humans, which has been envisaged to be due to formation of its reactive metabolites, essentially based on its structural similarity to benzbromarone, a drug withdrawn from the market due to reasons of similar hepatotoxicity. Therefore, the purpose of this study was to detect glutathione conjugates of amiodarone and its reactive diquinone metabolites in rat bile using mass spectrometry tools. METHODS: Wistar rats were dosed orally with an amiodarone suspension and bile was collected via bile duct cannulation followed by solid-phase extraction, protein precipitation and centrifugation...
May 30, 2016: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/28300627/serum-uric-acid-is-associated-with-better-executive-function-in-men-but-not-in-women-baseline-assessment-of-the-elsa-brasil-study
#13
Cristina Pellegrino Baena, Claudia Kimie Suemoto, Sandhi Maria Barreto, Paulo Andrade Lotufo, Isabela Benseñor
BACKGROUND: Serum uric acid (SUA) may protect against free radical stress damage and was previously linked to cognitive impairment in older adults, but evidence in middle-aged adults is scarce. PURPOSE: We sought to analyze whether SUA is associated with cognitive performance in apparently healthy middle-aged participants in the ELSA-Brasil cohort study. METHODS: We excluded participants older than age 65, those taking allopurinol, benzbromarone, or medications that could impair cognitive performance, those with previous stroke, and those with incomplete data on cognitive tests or SUA...
June 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28250317/strategic-drug-design-to-avoid-the-metabolic-activation-of-hepatotoxic-drugs
#14
REVIEW
Tomoyuki Ohe, Kyoko Takahashi, Shigeo Nakamura, Tadahiko Mashino
 Adverse reactions are one of the most important issues in drug development, as well as in the therapeutic usage of drugs during the post-approval stage. Specifically, idiosyncratic adverse drug reactions (IDR) occur in only a small group of patients who are treated with certain drugs, and are unpredictable. It is widely accepted that drug-induced IDR is often associated with CYP-mediated bioactivation. Benzbromarone (BBR) is effective in the treatment of hyperuricemia, and has been used as an effective drug in Japan for a long time...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28202260/allopurinol-benzbromarone-and-risk-of-coronary-heart-disease-in-gout-patients-a-population-based-study
#15
Hsiu-Chen Lin, Masao Daimon, Ching-Hung Wang, Yi Ho, Yow-Shieng Uang, Shuo-Ju Chiang, Li-Hsuan Wang
BACKGROUND: The effect of gout on the risk of developing coronary artery disease (CAD) is uncertain. Some studies have found that gout is a risk factor for acute myocardial infarction. This study examined the changes in risk of CAD in gout patients taking allopurinol and/or benzbromarone, and analyzed the dose-response relationship of both drugs with CAD incidence. METHODS: The medical records of one million subjects from 2000 to 2011 were provided by the Taiwan National Health Insurance Research Database...
April 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28131653/identification-of-novel-glutathione-adducts-of-benzbromarone-in-human-liver-microsomes
#16
Naoki Cho, Kaoru Kobayashi, Mina Yoshida, Noriyuki Kogure, Hiromitsu Takayama, Kan Chiba
Benzbromarone (BBR) is a potent uricosuric drug that can cause serious liver injury. Our recent study suggested that 1'-hydroxy BBR, one of major metabolites of BBR, is metabolized to a cytotoxic metabolite that could be detoxified by glutathione (GSH). The aim of this study was to clarify whether GSH adducts are formed from 1'-hydroxy BBR in human liver microsomes (HLM). Incubation of 1'-hydroxy BBR with GSH in HLM did not result in the formation of GSH adducts, but 1',6-dihydroxy BBR was formed. In addition, incubation of 1',6-dihydroxy BBR with GSH in HLM resulted in the formation of three novel GSH adducts (M1, M2 and M3)...
February 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28116659/effect-of-rhizoma-polygoni-cuspidati-and-ramulus-cinnamomi-compatibility-on-uric-acid-metabolism-and-urinary-neutrophil-gelatinase-associated-lipocalin-and-kidney-injury-molecule-1-in-rats-with-hyperuricemia
#17
Bin Han, Chun-Xia Zhu, Wan Shi, Hui-Zhu Huang, Xu-Guang Hu, Xiao-Ming Zhou, Ming Lei, Zhong Li
OBJECTIVE: To explore the effects of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomi compatibility (PR) on uric acid metabolism and the expression of urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in rats with hyperuricemia. METHODS: Seventy male Sprague Dawley (SD) rats were randomly divided into 7 groups with 10 rats per group, including the normal group, model group, allopurinol group, benzbromarone group and PR groups at 3 doses (3...
January 24, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28109183/chloride-ion-transport-and-overexpression-of-tmem16a-in-a-guinea-pig-asthma-model
#18
M Kondo, M Tsuji, K Hara, K Arimura, O Yagi, E Tagaya, K Takeyama, J Tamaoki
BACKGROUND: TMEM16A, a Ca-activated Cl channel, regulates various physiological functions such as mucin secretion. However, the role of TMEM16A in hyper-secretion in asthma is not fully understood. OBJECTIVE: The aim of this study is to evaluate Cl ion transport via TMEM16A and determine the localization of TMEM16A in a guinea-pig asthma model. METHODS: Guinea-pigs were sensitized with ovalbumin (OVA) i.p. on Days 1 and 8. On Day 22, we assessed OVA challenge-induced Cl ion transport in the sensitized tracheas ex vivo in an Ussing chamber, compared with the non-sensitized tracheas...
January 21, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28104163/hyperuricemia-and-acute-renal-failure-in-renal-transplant-recipients-treated-with-high-dose-mizoribine
#19
K Akioka, T Ishikawa, M Osaka, Y Kadotani, K Okugawa, K Nakano, Y Osaka, K Tsuchiya, H Sako
BACKGROUND: Hyperuricemia is a common adverse event frequently found in renal transplant recipients with mizoribine (MZ). Hyperuricemia itself will be a cause of renal dysfunction, and renal dysfunction also will be a cause of hyperuricemia simultaneously. This study investigates frequency of hyperuricemia and renal failure in renal transplant recipients treated with high-dose MZ. PATIENTS AND METHODS: From December 2007 to October 2015, there was a total of 32 living related renal transplant recipients treated with high-dose MZ...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/27989145/cysteine-based-protein-adduction-by-epoxide-derived-metabolite-s-of-benzbromarone
#20
Hui Wang, Yukun Feng, Qian Wang, Xiucai Guo, Wenlin Huang, Ying Peng, Jiang Zheng
Benzbromarone (BBR) is a therapeutically useful uricosuric agent but can also cause acute liver injury. The hepatotoxicity of BBR is suggested to be associated with its metabolic activation. Our recent metabolic study demonstrated that BBR was metabolized to epoxide intermediate(s) by cytochrome P450 3A, and the intermediate(s) was reactive to N-acetylcysteine. The objectives of the present study were to determine the chemical identity of the interaction of protein with the epoxide intermediate(s) of BBR and to define the association of the protein modification with hepatotoxicity induced by BBR...
December 19, 2016: Chemical Research in Toxicology
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