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https://www.readbyqxmd.com/read/28801519/xor-inhibition-with-febuxostat-accelerates-pulmonary-endothelial-barrier-recovery-and-improves-survival-in-lipopolysaccharide-induced-murine-sepsis
#1
Mahendra Damarla, Laura F Johnston, Gigi Liu, Li Gao, Lan Wang, Lidenys Varela, Todd M Kolb, Bo S Kim, Rachel L Damico, Paul M Hassoun
Sepsis is a leading cause of death among patients in the intensive care unit, resulting from multi-organ failure. Activity of xanthine oxidoreductase (XOR), a reactive oxygen species (ROS) producing enzyme, is known to be elevated in nonsurvivors of sepsis compared to survivors. We have previously demonstrated that XOR is critical for ventilator-induced lung injury. Using febuxostat, a novel nonpurine inhibitor of XOR, we sought to determine the role of XOR inhibition in a murine model of sepsis-induced lung injury and mortality...
August 2017: Physiological Reports
https://www.readbyqxmd.com/read/28693909/synthesis-and-evaluation-of-1-phenyl-1h-1-2-3-triazole-4-carboxylic-acid-derivatives-as-xanthine-oxidase-inhibitors
#2
Ting-Jian Zhang, Qing-Xia Wu, Song-Ye Li, Lin Wang, Qi Sun, Yi Zhang, Fan-Hao Meng, Hua Gao
This study mainly focused on the modification of the X(2) position in febuxostat analogs. A series of 1-phenyl-1H-1,2,3-triazole-4-carboxylic acid derivatives (1a-s) with an N atom occupying the X(2) position was designed and synthesized. Evaluation of their inhibitory potency in vitro on xanthine oxidase indicated that these compounds exhibited micromolar level potencies, with IC50 values ranging from 0.21µM to 26.13μM. Among them, compound 1s (IC50=0.21μM) showed the most promising inhibitory effects and was 36-fold more potent than allopurinol, but was still 13-fold less potent than the lead compound Y-700, which meant that a polar atom fused at the X(2) position could be unfavorable for potency...
June 23, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28689430/current-and-future-therapies-for-gout
#3
Tristan Pascart, Pascal Richette
Gout is a common disease responsible for recurrent flares triggered by the deposition of monosodium urate crystals secondary to longstanding hyperuricaemia. The management of gout implies both the treatment of flares and the treatment of hyperuricaemia itself. Recent improvement in the understanding of the disease led to the development of new drugs. Areas covered: This review covers data related to 'old' treatments of flares and hyperuricaemia, evidence on the recently approved drugs and emerging therapies in development...
July 28, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28682028/-the-uric-acid-cardio-nephropathy
#4
Francesca Viazzi, Barbara Bonino, Francesca Cappadona, Roberto Pontremoli
Uric acid is a product of purine catabolism formed by the activity of xanthine-oxidase and prevalently excreted by the kidney. In vivo, urate is known to have both an anti- or pro-oxidant role depending on several biological conditions. New evidence suggests that chronic hyperuricemia can contribute to hypertension development, kidney disease and cardiovascular risk. The pathophysiologic mechanisms are various, such as endothelial dysfunction and oxidative stress, vasoconstriction and stimulation of renin angiotensin system...
March 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28679982/pseudomelanosis-duodeni-a-case-report
#5
Masaya Iwamuro, Shohei Oka, Hiromitsu Kanzaki, Takehiro Tanaka, Seiji Kawano, Yoshiro Kawahara, Hiroyuki Okada
An 83-year-old Japanese man underwent esophagogastroduodenoscopy for screening purposes. He had a medical history of hypertension, chronic kidney disease, chronic heart failure, and chronic myeloid leukemia, and he had been taking the following medications:ferrous citrate, furosemide, spironolactone, tolvaptan, bisoprolol, nicorandil, warfarin, nilotinib, febuxostat, esomeprazole, digestive enzyme complex, ambroxol, carbocysteine, and potassium L-aspartate. Esophagogastroduodenoscopy revealed a brownish speckled pigmentation in the duodenal bulb...
2017: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
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
#6
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/28631197/prioritizing-future-research-on-allopurinol-and-febuxostat-for-the-management-of-gout-value-of-information-analysis
#7
Eric Jutkowitz, Fernando Alarid-Escudero, Hyon K Choi, Karen M Kuntz, Hawre Jalal
OBJECTIVES: The aim of this study was to quantify the value of conducting additional research and reducing uncertainty regarding the cost effectiveness of allopurinol and febuxostat for the management of gout. METHODS: We used a previously developed Markov model that evaluated the cost effectiveness of nine urate-lowering strategies: no treatment, allopurinol-only fixed dose (300 mg), allopurinol-only dose escalation (up to 800 mg), febuxostat-only fixed dose (80 mg), febuxostat-only dose escalation (up to 120 mg), allopurinol-febuxostat sequential therapy fixed dose, allopurinol-febuxostat sequential therapy dose escalation, febuxostat-allopurinol sequential therapy fixed dose, and febuxostat-allopurinol sequential therapy dose escalation...
June 19, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28603225/cross-over-trial-of-febuxostat-and-topiroxostat-for-hyperuricemia-with-cardiovascular-disease-trofeo-trial
#8
Akira Sezai, Kazuaki Obata, Keisuke Abe, Sakie Kanno, Hisakuni Sekino
BACKGROUND: We previously reported that febuxostat was more effective for hyperuricemia than allopurinol. The efficacy, however, of topiroxostat (a novel xanthine oxidase reductase inhibitor similar to febuxostat), for hyperuricemia is unknown.Methods and Results:Patients with cardiovascular disease and hyperuricemia, in whom serum uric acid (s-UA) was controlled at ≤6 mg/dL, were eligible for enrollment. Fifty-five patients were randomized to receive either febuxostat or topiroxostat for 6 months and were switched to the other drug for the following 6 months...
June 9, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28597604/lesinurad-a-selective-uric-acid-reabsorption-inhibitor-in-combination-with-febuxostat-in-patients-with-tophaceous-gout-findings-of-a-phase-iii-clinical-trial
#9
Nicola Dalbeth, Graeme Jones, Robert Terkeltaub, Dinesh Khanna, Jeff Kopicko, Nihar Bhakta, Scott Adler, Maple Fung, Chris Storgard, Scott Baumgartner, Fernando Perez-Ruiz
OBJECTIVE: To investigate the efficacy and safety of lesinurad in combination with febuxostat in a 12-month phase III trial in patients with tophaceous gout. METHODS: Patients with serum urate (UA) ≥8.0 mg/dl (≥6.0 mg/dl with urate-lowering therapy) and ≥1 measurable target tophus were given febuxostat 80 mg/day for 3 weeks before randomization to receive lesinurad (200 or 400 mg daily) or placebo in addition to the febuxostat. The primary end point was the proportion of patients achieving a serum UA level of <5...
June 9, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28584186/comparative-effectiveness-of-allopurinol-versus-febuxostat-for-preventing-incident-renal-disease-in-older-adults-an-analysis-of-medicare-claims-data
#10
Jasvinder A Singh, John D Cleveland
OBJECTIVE: To assess the comparative effectiveness of allopurinol versus febuxostat for preventing incident renal disease in elderly. METHODS: In a retrospective cohort study using 2006-2012 Medicare claims data, we included patients newly treated with allopurinol or febuxostat (baseline period of 183 days without either medication). We used 5:1 propensity-matched Cox regression analyses to compare the HR of incident renal disease with allopurinol use (and dose) versus febuxostat (reference)...
June 5, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28578274/synthesis-and-characterization-of-a-novel-organic-nitrate-ndhp-role-of-xanthine-oxidoreductase-mediated-nitric-oxide-formation
#11
Zhengbing Zhuge, Luciano L Paulo, Arghavan Jahandideh, Maria C R Brandão, Petrônio F Athayde-Filho, Jon O Lundberg, Valdir A Braga, Mattias Carlström, Marcelo F Montenegro
In this report, we describe the synthesis and characterization of 1,3-bis(hexyloxy)propan-2-yl nitrate (NDHP), a novel organic mono nitrate. Using purified xanthine oxidoreductase (XOR), chemiluminescence and electron paramagnetic resonance (EPR) spectroscopy, we found that XOR catalyzes nitric oxide (NO) generation from NDHP under anaerobic conditions, and that thiols are not involved or required in this process. Further mechanistic studies revealed that NDHP could be reduced to NO at both the FAD and the molybdenum sites of XOR, but that the FAD site required an unoccupied molybdenum site...
May 26, 2017: Redox Biology
https://www.readbyqxmd.com/read/28566603/febuxostat-for-the-prevention-of-recurrent-2-8-dihydroxyadenine-nephropathy-due-to-adenine-phosphoribosyltransferase-deficiency-following-kidney-transplantation
#12
Koji Nanmoku, Akira Kurosawa, Takahiro Shinzato, Toshihiro Shimizu, Takaaki Kimura, Takashi Yagisawa
Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder that results in irreversible renal damage due to 2,8-dihydroxyadenine (DHA) nephropathy. A 28-year-old man underwent living-related kidney transplantation for chronic kidney disease of unknown etiology. Numerous spherical brownish crystals observed in his urinary sediment on postoperative day 3 and were observed within the tubular lumen of renal allograft biopsy specimens on postoperative day 7. After a genetic diagnosis, febuxostat treatment was started on postoperative day 7, with the dosage gradually increased to 80 mg/day until complete the disappearance of 2,8-DHA crystals...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28544467/a-survey-on-the-beliefs-and-knowledge-of-gout-management-in-new-medical-graduates-new-south-wales-australia
#13
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/28532636/erratum-regarding-febuxostat-in-hyperuricemic-patients-with-advanced-ckd-am-j-kidney-dis-2016-68-5-819-821
#14
(no author information available yet)
No abstract text is available yet for this article.
June 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28521802/identification-of-chronic-kidney-disease-patient-characteristics-influencing-the-renoprotective-effects-of-febuxostat-therapy-a-retrospective-follow-up-study
#15
Akinori Yamaguchi, Makoto Harada, Yosuke Yamada, Koji Hashimoto, Yuji Kamijo
BACKGROUND: The ability of antihyperuricemic therapy to exert renoprotective effects in patients with chronic kidney disease (CKD) is controversial. In the present study, we studied patient characteristics that may mask favorable impact of antihyperuricemic therapy on the progression of CKD. METHODS: This was a single-center, retrospective, follow-up study. One-hundred and seventy-eight CKD patients with hyperuricemia who received febuxostat therapy were included in this study...
May 18, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28503330/febuxostat-attenuates-renal-damage-besides-exerting-hypouricemic-effect-in-streptozotocin-induced-diabetic-rats
#16
Jianmin Ran, Gang Xu, Huixuan Ma, Hailing Xu, Yan Liu, Rongshao Tan, Ping Zhu, Jun Song, Gancheng Lao
Aim. In this study, we aimed to investigate the effects of febuxostat, a novel inhibitor of xanthine oxidase (XO), on renal damage in streptozotocin- (STZ-) induced diabetic rats. Methods. Diabetes was induced by the intraperitoneal injection of STZ in male Sprague-Dawley rats. Sham-injected rats served as controls. The control and diabetic rats were treated with and without febuxostat for 8 weeks, respectively. Fasting blood and 24-h urine samples were collected every 4 weeks. Rat livers were extracted for detecting gene expression, content, and bioactivity of XO...
2017: International Journal of Nephrology
https://www.readbyqxmd.com/read/28485997/prophylaxis-of-acute-flares-when-initiating-febuxostat-for-chronic-gouty-arthritis-in-a-real-world-clinical-setting
#17
Jinquan Yu, Qian Qiu, Liuqin Liang, Xiuyan Yang, Hanshi Xu
OBJECTIVE: Flare prophylaxis is recommended during urate-lowering therapy (ULT) despite lack of proven benefit especially when initiating febuxostat. We investigated if colchicine or steroids administration during initiation of febuxostat for chronic gouty arthritis reduces the frequency and/or severity of acute gout flares. METHODS: Patients with confirmed diagnosis of gout starting febuxostat were retrospectively studied. Frequency, severity, and length of flares were analyzed...
May 9, 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/28463849/effect-of-febuxostat-on-the-endothelial-dysfunction-in-hemodialysis-patients-a-randomized-placebo-controlled-double-blinded-study
#18
Mona Alshahawey, Sara Mahmoud Shahin, Tamer Wahid Elsaid, Nagwa Ali Sabri
BACKGROUND: Endothelial dysfunction is an important risk factor for cardiovascular diseases to occur in end-stage renal disease patients. Febuxostat, being a novel xanthine oxidase inhibitor, is apparently having a beneficial role in improving the endothelial dysfunction; however, data among hemodialysis patients are still limited. METHODS: A prospective, placebo-controlled, block-randomized, double-blinded study was carried out to evaluate the effect of oral febuxostat on the endothelial dysfunction in hemodialysis patients...
2017: American Journal of Nephrology
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
#19
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/28458354/previous-dosage-of-allopurinol-is-a-strong-determinant-of-febuxostat-efficacy
#20
Hiroyoshi Koide, Daiki Hira, Masayuki Tsujimoto, Yurie Katsube, Tetsuya Minegaki, Takashi Uzu, Yoshito Ikeda, Shin-Ya Morita, Kohshi Nishiguchi, Tomohiro Terada
Febuxostat has currently played pivotal role in the treatment of hyperuricemia, but there is little comprehensive information for the determinants of individual difference in efficacy of febuxostat. Therefore, the present study, a retrospective investigation, was carried out to analyze the effects of patient characteristics on the efficacy of febuxostat. A total of 225 patients who were continuously prescribed the same dose of febuxostat for 8-12 weeks from the initial therapy were enrolled in the present study...
2017: Biological & Pharmaceutical Bulletin
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