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Margret Thorsteinsdottir, Unnur A Thorsteinsdottir, Finnur F Eiriksson, Hrafnhildur L Runolfsdottir, Inger M Sch Agustsdottir, Steinunn Oddsdottir, Baldur B Sigurdsson, Hordur K Hardarson, Nilesh R Kamble, Snorri Th Sigurdsson, Vidar O Edvardsson, Runolfur Palsson
Adenine phosphoribosyltransferase (APRT) deficiency is a hereditary disorder that leads to excessive urinary excretion of 2,8-dihydroxyadenine (DHA), causing nephrolithiasis and chronic kidney disease. Treatment with allopurinol or febuxostat reduces DHA production and attenuates the renal manifestations. Assessment of DHA crystalluria by urine microscopy is used for therapeutic monitoring, but lacks sensitivity. We report a high-throughput assay based on ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) for quantification of urinary DHA...
September 14, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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
Andrew Finch Rheumatology, Paul Kubler Rheumatologist
Gout is a common inflammatory arthritis that is increasing in prevalence. It is caused by the deposition of urate crystals. Non-steroidal anti-inflammatory drugs, colchicine and corticosteroids are options for the management of acute gout. They are equally efficacious and comorbidities guide the best choice. Allopurinol is an effective treatment for reducing concentrations of uric acid. Renal function guides the starting dose of allopurinol and the baseline serum uric acid concentration guides the maintenance dose...
August 2016: Australian Prescriber
Bishoy Kamel, Garry G Graham, Kenneth M Williams, Kevin D Pile, Richard O Day
Febuxostat is a xanthine oxidoreductase inhibitor that has been developed to treat chronic gout. In healthy subjects, the pharmacokinetic parameters of febuxostat after multiple oral dose administration include an oral availability of about 85 %, an apparent oral clearance (CL/F) of 10.5 ± 3.4 L/h and an apparent volume of distribution at steady state (V ss/F) of 48 ± 23 L. The time course of plasma concentrations follows a two-compartment model. The initial half-life (t ½) is approximately 2 h and the terminal t ½ determined at daily doses of 40 mg or more is 9...
October 17, 2016: Clinical Pharmacokinetics
Christa Zollbrecht, A Erik G Persson, Jon O Lundberg, Eddie Weitzberg, Mattias Carlström
BACKGROUND: Inorganic nitrite has shown beneficial effects in cardiovascular and metabolic diseases partly via attenuation of NADPH-oxidase (NOX)-mediated oxidative stress. However, the exact mechanisms are still unclear. Here we investigated the role of S-nitrosation or altered expression of NOX subunits, and the role of xanthine oxidoreductase (XOR) in nitrite-derived nitric oxide (NO) production. METHODS: Mouse macrophages were activated with LPS in the presence or absence of nitrite...
September 28, 2016: Redox Biology
A-K Tausche, M Aringer
Gouty arthritis is the most common form of arthritis in men. As a consequence of persisting hyperuricemia, uric acid crystals are deposited in the intra-articular and periarticular spaces and activate the innate immune system. The clinically impressive abrupt onset monoarticular arthritis in the lower extremities is highly suggestive of a gout attack. Arthrosonography can be used for early detection of crystal deposition on joint cartilage. In synovial fluid the detection of uric acid crystals in polarization microscopy is proof of gout even without the detection of intracellular uric acid crystals...
October 11, 2016: Zeitschrift Für Rheumatologie
Meenu Pichholiya, Arvind Kumar Yadav, S K Luhadia, Jameela Tahashildar, M L Aseri
OBJECTIVES: To compare the efficacy and safety of febuxostat and allopurinol in pyrazinamide (PZA)-induced hyperuricemia in patients taking antitubercular therapy (ATT). METHODS: This randomized controlled study was conducted at a tertiary care teaching institute of Rajasthan in all the sputum-positive tubercular patients aged between 18 and 65 years of either sex. Serum uric acid level was monitored at 0(th), 2(nd), 4(th), 6(th), and 8(th) week of ATT. Patients whose uric acid level was found to be increased at 2(nd) week were finally recruited in the study...
September 2016: Indian Journal of Pharmacology
Hyun Seon Kim, Sun Woo Lim, Long Jin, Jian Jin, Byung Ha Chung, Chul Woo Yang
BACKGROUND: The use of calcineurin inhibitors is a well-known risk factor for hyperuricemia in kidney transplant recipients. We evaluated the effect of febuxostat (Fx), a new uric acid-lowering drug, on hyperuricemia and renal injury in an experimental model of chronic tacrolimus (Tac)-induced nephropathy. METHODS: Chronic Tac nephropathy was induced by administering Tac (1.5 mg/kg/day) to rats on a low-salt diet (0.05%) with oxonic acid (OA, 2%, 0.2 g/kg/day) for 28 days...
October 5, 2016: Nephron
Samir G Mallat, Sahar Al Kattar, Bassem Y Tanios, Abdo Jurjus
Uric acid is a product of purine metabolism and has been linked to gout and kidney calculi. Chronic kidney disease (CKD) and hypertension (HTN) are two major public health problems, and both are associated with increased risk of cardiovascular events. Emerging evidence suggests a pathogenic role of hyperuricemia in the development of HTN and CKD, in addition to progression of CKD, by inducing renal inflammation, endothelial dysfunction, and activation of the renin-angiotensin system. In addition, several epidemiological studies have linked hyperuricemia with an increased risk of HTN and CKD...
October 2016: Current Hypertension Reports
Li-Hui Qu, Hong Jiang, Jiang-Hua Chen
BACKGROUND: The purpose of this meta-analysis was to determine if uric acid-lowering therapy is associated with a decrease in blood pressure (BP) and serum creatinine levels. MATERIALS AND METHODS: Medline, Cochrane, EMBASE, and Google Scholar databases were searched until June 29, 2016, with keywords: uric-acid-lowering therapy, allopurinol, febuxostat, uricosuric, blood pressure. Only randomized controlled trials were included. The primary outcomes were reduction in systolic BP (SBP) and diastolic BP (DBP), and secondary was reduction in serum creatinine level...
September 30, 2016: Annals of Medicine
Yeong-Hau H Lien, Joy L Logan
No abstract text is available yet for this article.
September 22, 2016: American Journal of Medicine
Takeo Yasu, Shunsuke Kobayashi, Mai Horii, Yosuke Kurokawa
Tumor lysis syndrome (TLS) is a life-threatening oncologic emergency. The control of serum uric acid level (UA) is important for prevention of TLS. Febuxostat has demonstrated its superiority over allopurinol in decreasing UA level. We retrospectively evaluated the efficacy of febuxostat 10 mg in prevention of hyperuricemia associated with TLS (HU-TLS) in 12 patients with non-Hodgkin's lymphoma (NHL). Mean UA levels were found to significantly decrease (p = 0.003). HU-TLS was prevented in all patients. Thus, febuxostat 10 mg is effective in prevention of HU-TLS...
September 19, 2016: International Journal of Clinical Pharmacology and Therapeutics
Maria Peleli, Christa Zollbrecht, Marcelo F Montenegro, Michael Hezel, Jianghong Zhong, Erik G Persson, Rikard Holmdahl, Eddie Weitzberg, Jon O Lundberg, Mattias Carlström
Xanthine oxidoreductase (XOR) is generally known as the final enzyme in purine metabolism and as a source of reactive oxygen species (ROS). In addition, this enzyme has been suggested to mediate nitric oxide (NO) formation via reduction of inorganic nitrate and nitrite. This NO synthase (NOS)-independent pathway for NO generation is of particular importance during certain conditions when NO bioavailability is diminished due to reduced activity of endothelial NOS (eNOS) or increased oxidative stress, including aging and cardiovascular disease...
September 5, 2016: Free Radical Biology & Medicine
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
Devang Tandel, Purvi Shah, Kalpana Patel, Vaishali Thakkar, Kirti Patel, Tejal Gandhi
A rapid and sensitive reversed-phase high-performance liquid chromatography (HPLC) method using novel salting-out assisted liquid-liquid extraction technique has been developed for the quantitative determination of febuxostat (FEB), used for the treatment of gout, in rat plasma. The method was validated according to US FDA guideline. Separation was achieved using a Phenomenex Luna-C18 (250 × 4.60 mm, 5 µm) column and mobile phase composed of potassium dihydrogen orthophosphate buffer 25 mM, adjusted to pH 6...
September 6, 2016: Journal of Chromatographic Science
Lucas C Pinheiro, Gustavo H Oliveira-Paula, Rafael L Portella, Danielle A Guimarães, Celio D de Angelis, Jose E Tanus-Santos
Proton pump inhibitors (PPIs) are widely used drugs that may increase the cardiovascular risk by mechanisms not entirely known. While PPIs increase asymmetric dimethylarginine (ADMA) levels and inhibit nitric oxide production, it is unknown whether impaired vascular redox biology resulting of increased xanthine oxidoreductase (XOR) activity mediates PPIs-induced endothelial dysfunction (ED). We examined whether increased XOR activity impairs vascular redox biology and causes ED in rats treated with omeprazole...
August 4, 2016: Redox Biology
Magnus Diller, Martin Fleck
Muskuloskeletal ultrasound and dual-energy-CT (DECT) findings are increasingly relevant for the establishment of the diagnosis of gout, and are therefore incorporated into the novel ACR / EULAR classification criteria. Canakinumab, a monoclonal antibody directed against interleukin-1β (IL-1β) has been approved in 2013 for the treatment of acute gout and for prophylaxis of flares. In patients demonstrating an inadequate response upon treatment with allopurinol or febuxostat, combination therapy with lesinurad might reduce uric acid levels to the target of < 6 mg / dl (< 5 mg / dl in tophaceous gout)...
August 2016: Deutsche Medizinische Wochenschrift
Sebastian E Sattui, Angelo L Gaffo
Despite being the most common type of inflammatory arthritis, gout is often poorly managed. Except for febuxostat and pegloticase, research in new therapeutic agents for the management of hyperuricemia in gout remained insufficient for several decades. With emerging evidence of possible roles of hyperuricemia in cardiometabolic comorbidities, as well as more convincing evidence regarding poor outcomes (e.g. disability, recurrent hospital admissions) in patients with uncontrolled gout, several agents are current under development...
August 2016: Therapeutic Advances in Musculoskeletal Disease
Mileta Poskurica, Dejan Petrović, Mina Poskurica
`Hematologic malignancies (leukemia, lymphoma, multiple myeloma, et al.), as well as solid tumours (renal, liver, lung, ovarian, etc.), can lead to acute or chronic renal failure.The most common clinical manifestation is acute renal failure within the tumour lysis syndrome (TLS). It is characterized by specific laboratory and clinical criteria in order to prove that kidney disorders result from cytolysis of tumour cells after chemotherapy regimen given, although on significantly fewer occasions it is likely to occur spontaneously or after radiotherapy...
March 2016: Srpski Arhiv za Celokupno Lekarstvo
P Richette, M Doherty, E Pascual, V Barskova, F Becce, J Castañeda-Sanabria, M Coyfish, S Guillo, T L Jansen, H Janssens, F Lioté, C Mallen, G Nuki, F Perez-Ruiz, J Pimentao, L Punzi, T Pywell, A So, A K Tausche, T Uhlig, J Zavada, W Zhang, F Tubach, T Bardin
BACKGROUND: New drugs and new evidence concerning the use of established treatments have become available since the publication of the first European League Against Rheumatism (EULAR) recommendations for the management of gout, in 2006. This situation has prompted a systematic review and update of the 2006 recommendations. METHODS: The EULAR task force consisted of 15 rheumatologists, 1 radiologist, 2 general practitioners, 1 research fellow, 2 patients and 3 experts in epidemiology/methodology from 12 European countries...
July 25, 2016: Annals of the Rheumatic Diseases
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