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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...
February 12, 2017: International Journal of Cardiology
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)...
October 27, 2016: Drug Metabolism and Pharmacokinetics
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
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
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
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
James M Lipchock, Heidi P Hendrickson, Bonnie B Douglas, Kelly E Bird, Patrick S Ginther, Ivan Rivalta, Nicholas S Ten, Victor S Batista, J Patrick Loria
Protein tyrosine phosphatase 1B (PTP1B) is a known regulator of the insulin and leptin signaling pathways and is an active target for the design of inhibitors for the treatment of type II diabetes and obesity. Recently, cichoric acid (CHA) and chlorogenic acid (CGA) were predicted by docking methods to be allosteric inhibitors that bind distal to the active site. However, using a combination of steady-state inhibition kinetics, solution nuclear magnetic resonance experiments, and molecular dynamics simulations, we show that CHA is a competitive inhibitor that binds in the active site of PTP1B...
January 10, 2017: Biochemistry
Qinghua Hu, Mengze Zhou, Haoran Zhu, Guo Lu, Dongsen Zheng, Huanqiu Li, Kun Hao
Hyperuricemia is a kind of metabolic disease resulted from imbalance between urate production and excretion. Xanthine oxidase (XOD) or renal urate transporter 1 (URAT1) inhibitors have been applied for hyperuricemia treatment in clinic, but available drugs could not simultaneously target XOD and URAT1 and had various adverse effects. (E)-2-(4-bromophenyl)-1-(2, 4-dihydroxyphenyl)ethanone oxime (BDEO), as a deoxybenzoins oxime analog, was obtained from a cluster of deoxybenzoins derivatives synthesized by our research group with potent anti-hyperuricemic activity, which was expected to be dual inhibitor of XOD and URAT1...
February 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Qiao Zhou, Jiang Su, Ting Zhou, Juan Tian, Xixi Chen, Jing Zhu
OBJECTIVE: To evaluate and compare the safety and efficacy of three urate lowering agents: febuxostat, allopurinol, and benzbromarone, when used to treat Chinese gout patients. METHODS: A total of 120 patients treated in our department from November 2011 to December 2014 were randomly selected and divided into four groups: febuxostat (40 mg per day), febuxostat (80 mg per day), allopurinol (100 mg, 3 × per day) or benzbromarone (50 mg per day), (n = 30 patients/group)...
February 2017: International Journal of Clinical Pharmacology and Therapeutics
Jeroen Brijs, Grant W Hennig, Anna-Maria Kellermann, Michael Axelsson, Catharina Olsson
Rhythmic contractions of the mammalian gastrointestinal tract can occur in the absence of neuronal or hormonal stimulation due to the generation of spontaneous electrical activity by interstitial cells of Cajal (ICC) that are electrically coupled to smooth muscle cells. The myogenically-driven component of gastrointestinal motility patterns in fish likely also involves ICC, however, little is known of their presence, distribution and function in any fish species. In the present study, we combined immunohistochemistry and in vivo recordings of intestinal motility to investigate the involvement of ICC in the motility of the proximal intestine in adult shorthorn sculpin (Myoxocephalus scorpius)...
November 10, 2016: Journal of Experimental Biology
Yuko Ohta, Azusa Ishizuka, Hisatomi Arima, Shinichiro Hayashi, Yoshio Iwashima, Masatsugu Kishida, Fumiki Yoshihara, Satoko Nakamura, Yuhei Kawano
Uric acid (UA) has been associated with hypertension, renal disease and cardiovascular disease. The aim of the present study was to compare the UA-lowering effects of a standard dose of the UA synthesis inhibitor febuxostat to a standard dose of the uricosuric agent benzbromarone, and to investigate the effects of a low-dose combination of both agents in hypertensive patients with hyperuricemia. Twenty hypertensive patients with inadequate UA control were administered febuxostat 40 mg (Feb), benzbromarone 50 mg (Ben) and febuxostat 20 mg and benzbromarone 25 mg (feb/ben) for 3 months each in a randomized modified crossover manner...
October 20, 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Jeffrey Miner, Philip K Tan, David Hyndman, Sha Liu, Cory Iverson, Payal Nanavati, David T Hagerty, Kimberly Manhard, Zancong Shen, Jean-Luc Girardet, Li-Tain Yeh, Robert Terkeltaub, Barry Quart
BACKGROUND: Excess body burden of uric acid promotes gout. Diminished renal clearance of uric acid causes hyperuricemia in most patients with gout, and the renal urate transporter (URAT)1 is important for regulation of serum uric acid (sUA) levels. The URAT1 inhibitors probenecid and benzbromarone are used as gout therapies; however, their use is limited by drug-drug interactions and off-target toxicity, respectively. Here, we define the mechanism of action of lesinurad (Zurampic®; RDEA594), a novel URAT1 inhibitor, recently approved in the USA and Europe for treatment of chronic gout...
October 3, 2016: Arthritis Research & Therapy
Sunao Kojima, Shinobu Kojima, Atsuko Hifumi, Hirofumi Soejima, Hisao Ogawa
No abstract text is available yet for this article.
December 1, 2016: International Journal of Cardiology
Shu Li, Hongxi Yang, Yanan Guo, Fengjiang Wei, Xilin Yang, Daiqing Li, Mingzhen Li, Weili Xu, Weidong Li, Li Sun, Ying Gao, Yaogang Wang
The prevalence of hyperuricemia and gout has been increasing, but the comparative effectiveness and safety of different treatments remain uncertain. We aimed to compare the effectiveness and safety of different treatments for hyperuricemia using network meta-analysis methodology. We systematically reviewed fifteen randomized controlled trials (involving 7,246 patients through January 2016) that compared the effects of different urate-lowering drugs (allopurinol, benzbromarone, febuxostat, pegloticase and probenecid) on hyperuricemia...
2016: Scientific Reports
Huey-En Tzeng, Che-Chen Lin, I-Kuan Wang, Po-Hao Huang, Chun-Hao Tsai
There is still debate on whether high uric acid increases bone mineral density (BMD) against osteoporotic fracture or bone resorption caused by gout inflammation. This study aimed to evaluate whether gout offers a protective effect on bone health or not. We conducted a nationwide population-based retrospective cohort study to evaluate the association between gout history and risk factors of fracture.A retrospective cohort study was designed using the claim data from Longitudinal Health Insurance Database (LHID)...
August 2016: Medicine (Baltimore)
Tae Sik Sung, Kate O'Driscoll, Haifeng Zheng, Nicholas J Yapp, Normand Leblanc, Sang Don Koh, Kenton M Sanders
Anoctamin-1 (ANO1) is a Ca(2+)-activated Cl(-) channel expressed in many types of cells. Splice variants of ANO1 have been shown to influence the biophysical properties of conductance. It has been suggested that several new antagonists of ANO1 with relatively high affinity and selectivity might be useful for experimental and, potentially, therapeutic purposes. We investigated the effects of intracellular Ca(2+) concentration ([Ca(2+)]i) at 100-1,000 nM, a concentration range that might be achieved in cells during physiological activation of ANO1 channels, on blockade of ANO1 channels expressed in HEK-293 cells...
September 1, 2016: American Journal of Physiology. Cell Physiology
Yuki Haga, Shin Yasui, Tatsuo Kanda, Noriyuki Hattori, Toru Wakamatsu, Masato Nakamura, Reina Sasaki, Shuang Wu, Shingo Nakamoto, Makoto Arai, Hitoshi Maruyama, Masayuki Ohtsuka, Shigeto Oda, Masaru Miyazaki, Osamu Yokosuka
On-line hemodiafiltration (OLHDF) is one of the treatment options in the management of acute liver failure (ALF) in Japan. It is essential to avoid infection in the management of ALF. In fact, infection is one of the prognostic factors in ALF. In this report, we present a middle-aged Japanese man with ALF associated with benzbromarone use. He was successfully managed without infection until liver transplantation by creating an arteriovenous fistula for OLHDF. Utilizing an arteriovenous fistula for OLHDF, rather than inserting a vascular access catheter, is a beneficial option to avoid infectious diseases in the management of ALF...
January 2016: Case Reports in Gastroenterology
L K Stamp, J Haslett, C Frampton, D White, D Gardner, S Stebbings, G Taylor, R Grainger, R Kumar, S Kumar, T Kain, D Porter, M Corkill, A Cathro, S Metcalfe, J Wyeth, N Dalbeth
BACKGROUND: Benzbromarone is a potent uricosuric but is not widely available due to concerns about hepatotoxicity. In Aotearoa New Zealand, benzbromarone has been available since April 2013, subject to funding restrictions, for patients with inadequate urate-lowering response or intolerance to allopurinol and probenecid. AIM: To assess the safety and efficacy of benzbromarone in a real-life setting. METHODS: All patients who received funding for benzbromarone from 1 April 2013 to 30 September 2014 were identified...
September 2016: Internal Medicine Journal
Laura C López, Olga Varea, Susanna Navarro, José A Carrodeguas, Natalia Sanchez de Groot, Salvador Ventura, Javier Sancho
Human Amylin, or islet amyloid polypeptide (hIAPP), is a small hormone secreted by pancreatic β-cells that forms aggregates under insulin deficiency metabolic conditions, and it constitutes a pathological hallmark of type II diabetes mellitus. In type II diabetes patients, amylin is abnormally increased, self-assembled into amyloid aggregates, and ultimately contributes to the apoptotic death of β-cells by mechanisms that are not completely understood. We have screened a library of approved drugs in order to identify inhibitors of amylin aggregation that could be used as tools to investigate the role of amylin aggregation in type II diabetes or as therapeutics in order to reduce β-cell damage...
June 18, 2016: International Journal of Molecular Sciences
Nikolaos Pagonas, Samad Kor, Felix S Seibert, Arnd Giese, Walter Zidek, Petra Reinke, Nina Babel, Frederic Bauer, Timm H Westhoff
BACKGROUND Hyperuricemia is very common after renal transplantation. It is associated with an increased risk of cardiovascular events and graft loss. To date, however, treatment is only recommended in symptomatic disease. MATERIAL AND METHODS We included 503 adult patients who underwent kidney transplantation at the Charité-Universitätsmedizin Berlin in this retrospective study. Patients were followed up for up to 120 months. All-cause mortality, graft survival, changes in level of serum uric acid (SUA), and estimated glomerular filtration rate (eGFR) were analyzed...
June 7, 2016: Annals of Transplantation: Quarterly of the Polish Transplantation Society
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