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https://www.readbyqxmd.com/read/27933340/enhancement-of-pharmacological-effects-of-uricosuric-agents-by-concomitant-treatment-with-pyrazinamide-in-rats
#1
Tetsuya Taniguchi, Naoki Ashizawa, Koji Matsumoto, Takashi Iwanaga
Our goal was to establish a model for the evaluation of the effects of uricosuric agents and to clarify the underlying mechanism(s). The effects of a uricosuric agent co-treated with pyrazinamide, an anti-tubercular agent, on urate handling were examined in rats. Furthermore, the effects of uricosuric agents on urate uptake were evaluated using the vesicles of rat renal brush-border membrane. Treatment with probenecid, at a dose of 100 mg/kg, significantly increased the urinary urate to creatinine ratio (UUA/UCRE) in pyrazinamide-treated rats although the same treatment did not produce any uricosuric effects in intact rats...
December 8, 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/27932279/severe-gout-strategies-and-innovations-for-effective-management
#2
Eliseo Pascual, Mariano Andrés, Janitzia Vázquez-Mellado, Nicola Dalbeth
Severe gout is characterised by frequent polyarticular flares, numerous tophi, joint damage, and musculoskeletal disability. This is a preventable condition and in many cases, represents a disease that has been insufficiently managed for years. Standard management recommendations may be insufficient for patients with severe gout; these patients frequently require intensive individualised pharmacological management with combinations of urate-lowering therapy and anti-inflammatory agents. In this article, we aim to integrate recent therapeutic advances to provide a practical framework for optimal management of severe gout...
December 5, 2016: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/27931959/imaging-of-gout-new-tools-and-biomarkers
#3
REVIEW
Elizabeth G Araujo, Bernhard Manger, Fernando Perez-Ruiz, Ralf G Thiele
While joint aspiration and crystal identification by polarizing microscopy remain the gold standard for diagnosing tophaceous gout, agreement among medical and ancillary health personnel examining synovial fluid using polarizing microscopy for the detection of monosodium urate (MSU) crystals appears to be poor. Imaging modalities, including conventional radiography (CR), ultrasonography (US), magnetic resonance imaging (MRI), and dual-energy computed tomography (DECT), have been found to provide information on the deposition of MSU crystals in tissues, and the consequences of such deposition...
August 2016: Best Practice & Research. Clinical Rheumatology
https://www.readbyqxmd.com/read/27929277/acute-monoarthritis-diagnosis-in-adults
#4
Jonathan A Becker, Jennifer P Daily, Katherine M Pohlgeers
Acute monoarthritis can be the initial manifestation of many joint disorders. The most common diagnoses in the primary care setting are osteoarthritis, gout, and trauma. It is important to understand the prevalence of specific etiologies and to use the appropriate diagnostic modalities. A delay in diagnosis and treatment, particularly in septic arthritis, can have catastrophic results including sepsis, bacteremia, joint destruction, or death. The history and physical examination can help guide the use of laboratory and imaging studies...
November 15, 2016: American Family Physician
https://www.readbyqxmd.com/read/27927043/allopurinol-insights-from-studies-of-dose-response-relationships
#5
Richard O Day, Diluk R W Kannangara, Sophie L Stocker, Jane E Carland, Kenneth M Williams, Garry G Graham
Gout is the most common inflammatory arthritis in men and is increasingly prevalent. Allopurinol is very effective at reducing plasma urate concentrations to a level sufficient to dissolve monosodium urate crystals. However, many patients fail to achieve a sufficient therapeutic response to allopurinol. Areas covered: This review covers the metabolism and pharmacokinetics of allopurinol and its active metabolite, oxypurinol and how these factors affect the plasma concentrations of urate at initiation and during long-term therapy with allopurinol...
December 7, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27926541/major-unanswered-questions-in-the-clinical-gout-field
#6
Lisa K Stamp
PURPOSE OF REVIEW: Although gout is one of the most common forms of inflammatory arthritis, it has been relatively neglected until recently. Despite progress in many areas of pathophysiology and genetics of gout and the development of new urate lowering therapies, there remain a number of unanswered clinical questions. With the resurgence of interest in gout it is important to recognize key aspects of gout management that remain challenging and require further research. RECENT FINDINGS: The unanswered clinical issues outlined in this review are basic aspects of gout management that clinicians treating people with gout face on a daily basis and include when urate lowering therapy should be commenced, the most appropriate target serum urate, use of prophylaxis when starting urate lowering therapy and the most appropriate urate lowering therapy, particularly for those with chronic kidney disease...
December 6, 2016: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/27922051/catalysis-and-structure-of-zebrafish-urate-oxidase-provide-insights-into-the-origin-of-hyperuricemia-in-hominoids
#7
Marialaura Marchetti, Anastasia Liuzzi, Beatrice Fermi, Romina Corsini, Claudia Folli, Valentina Speranzini, Francesco Gandolfi, Stefano Bettati, Luca Ronda, Laura Cendron, Rodolfo Berni, Giuseppe Zanotti, Riccardo Percudani
Urate oxidase (Uox) catalyses the first reaction of oxidative uricolysis, a three-step enzymatic pathway that allows some animals to eliminate purine nitrogen through a water-soluble compound. Inactivation of the pathway in hominoids leads to elevated levels of sparingly soluble urate and puts humans at risk of hyperuricemia and gout. The uricolytic activities lost during evolution can be replaced by enzyme therapy. Here we report on the functional and structural characterization of Uox from zebrafish and the effects on the enzyme of the missense mutation (F216S) that preceded Uox pseudogenization in hominoids...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27917897/blood-borne-phagocytes-internalize-urate-microaggregates-and-prevent-intravascular-netosis-by-urate-crystals
#8
Elmar Pieterse, Ivica Jeremic, Christine Czegley, Daniela Weidner, Mona H C Biermann, Susan Veissi, Christian Maueröder, Christine Schauer, Rostyslav Bilyy, Tetiana Dumych, Markus Hoffmann, Luis E Munoz, Anders A Bengtsson, Georg Schett, Johan van der Vlag, Martin Herrmann
Hyperuricemia is strongly linked to cardiovascular complications including atherosclerosis and thrombosis. In individuals with hyperuricemia, needle-shaped monosodium urate crystals (nsMSU) frequently form within joints or urine, giving rise to gouty arthritis or renal calculi, respectively. These nsMSU are potent instigators of neutrophil extracellular trap (NET) formation. Little is known on the mechanism(s) that prevent nsMSU formation within hyperuricemic blood, which would potentially cause detrimental consequences for the host...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27916277/the-cost-effectiveness-of-hla-b-5801-screening-to-guide-initial-urate-lowering-therapy-for-gout-in-the-united-states
#9
Eric Jutkowitz, Maureen Dubreuil, Na Lu, Karen M Kuntz, Hyon K Choi
OBJECTIVE: Positive HLA-B*5801 carriers are at greater risk of experiencing rare but severe allopurinol hypersensitivity syndrome (AHS) [i.e., Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)]; however, HLA-B*5801 prevalence and AHS risk vary by race/ethnicity. We evaluated the cost-effectiveness of HLA-B*5801 testing according to race/ethnicity in the United States. METHODS: We determined the cost-effectiveness of universal testing for HLA-B*5801 compared to no testing prior to the initiation of allopurinol per US major race/ethnicity groups...
November 1, 2016: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/27906639/ultrasonography-in-the-diagnosis-of-asymptomatic-hyperuricemia-and-gout
#10
J G Puig, L M Beltrán, C Mejía-Chew, D Tevar, R J Torres
Sonography has detected urate deposits in 34%-42% of the patients with asymptomatic hyperuricemia. This may prompt reclassification of asymptomatic hyperuricemia into "asymptomatic gout" and consideration of urate lowering therapy (ULT) to resolve urate deposits. In patients with gout and no visible tophi, sonography has detected urate deposits in half of the patients. This may allow diagnosing "tophaceous gout" and influencing the serum urate target level, prophylaxis to avoid acute gout flares during ULT, and clinical follow-up...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906637/prevalence-of-urat1-allelic-variants-in-the-roma-population
#11
Blanka Stiburkova, Dana Gabrikova, Pavel Čepek, Pavel Šimek, Pavol Kristian, Elizabeth Cordoba-Lanus, Felix Claverie-Martin
The Roma represents a transnational ethnic group, with a current European population of 8-10 million. The evolutionary process that had the greatest impact on the gene pool of the Roma population is called the founder effect. Renal hypouricemia (RHUC) is a rare heterogenous inherited disorder characterized by impaired renal urate reabsorption. The affected individuals are predisposed to recurrent episodes of exercise-induced nonmyoglobinuric acute kidney injury and nephrolithiasis. To date, more than 150 patients with a loss-of-function mutation for the SLC22A12 (URAT1) gene have been found, most of whom are Asians...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906636/urat1-uox-double-knockout-mice-are-experimental-animal-models-of-renal-hypouricemia-and-exercise-induced-acute-kidney-injury
#12
Makoto Hosoyamada, Yu Tsurumi, Hidenori Hirano, Naoko H Tomioka, Yuko Sekine, Takayuki Morisaki, Shunya Uchida
Renal hypouricemia (RHUC) is a hereditary disease characterized by a low level of plasma urate but with normal urinary urate excretion. RHUC type 1 is caused by mutations of the urate transporter URAT1 gene (SLC22A12). However, the plasma urate levels of URAT1 knockout mice are no different from those of wild-type mice. In the present study, a double knockout mouse, in which the URAT1 and uricase (Uox) genes were deleted (Urat1-Uox-DKO), were used as an experimental animal model of RHUC type 1 to investigate RHUC and excise-induced acute kidney injury (EIAKI)...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906623/orotate-orotic-acid-an-essential-and-versatile-molecule
#13
M Löffler, E A Carrey, E Zameitat
Orotate (OA) is well-known as a precursor in biosynthesis of pyrimidines; in mammals it is released from the mitochondrial dihydroorotate dehydrogenase (DHODH) for conversion to UMP by the cytoplasmic UMP synthase enzyme. OA is also a normal part of the diet, being found in milk and dairy products, and it is converted to uridine for use in the pyrimidine salvage pathway predominantly in liver, kidney and erythrocytes. Early research into nutrition identified orotate as "vitamin B13," and its use as a complex with organic cations or metal ions was promulgated in body-building, and in assisting therapies of metabolic syndromes...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906618/expression-of-a-human-npt1-slc17a1-missense-variant-which-increases-urate-export
#14
Masayuki Sakiyama, Hirotaka Matsuo, Shushi Nagamori, Wei Ling, Yusuke Kawamura, Akiyoshi Nakayama, Toshihide Higashino, Toshinori Chiba, Kimiyoshi Ichida, Yoshikatsu Kanai, Nariyoshi Shinomiya
Human sodium-dependent phosphate cotransporter type 1 (NPT1/SLC17A1) is one of the urate transporters in the kidney. Our recent study revealed that a common missense variant, I269T (rs1165196), of NPT1 decreases the risk of renal underexcretion gout. Moreover, we demonstrated that human NPT1 is localized to the apical membrane of the renal proximal tubule, and that I269T is the gain-of-function variant which increases the NPT1-mediated urate export. However, the mechanism by which I269T variant increases the urate export remains to be clarified...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27904786/a-targeted-metabolomics-assay-to-measure-eight-purines-in-the-diet-of-common-bottlenose-dolphins-tursiops-truncatus
#15
A J Ardente, T J Garrett, R S Wells, M Walsh, C R Smith, J Colee, R C Hill
Bottlenose dolphins managed under human care, human beings and Dalmatian dogs are prone to forming urate uroliths. Limiting dietary purine intake limits urate urolith formation in people and dogs because purines are metabolized to uric acid, which is excreted in urine. Managed dolphins develop ammonium urate nephroliths, whereas free-ranging dolphins do not. Free-ranging dolphins consume live fish, whereas managed dolphins consume different species that have been stored frozen and thawed. Differences in the purine content of fish consumed by dolphins under human care versus in the wild may be responsible for the difference in urolith prevalence...
October 2016: Journal of Chromatography & Separation Techniques
https://www.readbyqxmd.com/read/27903743/uric-acid-crystals-induce-placental-inflammation-and-alter-trophoblast-function-via-an-il-1-dependent-pathway-implications-for-fetal-growth-restriction
#16
Marie-Eve Brien, Cyntia Duval, Julia Palacios, Ines Boufaied, Andrée-Anne Hudon-Thibeault, Mathieu Nadeau-Vallée, Cathy Vaillancourt, Colin P Sibley, Vikki M Abrahams, Rebecca L Jones, Sylvie Girard
Excessive placental inflammation is associated with several pathological conditions, including stillbirth and fetal growth restriction. Although infection is a known cause of inflammation, a significant proportion of pregnancies have evidence of inflammation without any detectable infection. Inflammation can also be triggered by endogenous mediators, called damage associated molecular patterns or alarmins. One of these damage-associated molecular patterns, uric acid, is increased in the maternal circulation in pathological pregnancies and is a known agonist of the Nlrp3 inflammasome and inducer of inflammation...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27903742/p2y6-receptor-antagonist-mrs2578-inhibits-neutrophil-activation-and-aggregated-neutrophil-extracellular-trap-formation-induced-by-gout-associated-monosodium-urate-crystals
#17
Payel Sil, Craig P Hayes, Barbara J Reaves, Patrick Breen, Shannon Quinn, Jeremy Sokolove, Balázs Rada
Human neutrophils (polymorphonuclear leukocytes [PMNs]) generate inflammatory responses within the joints of gout patients upon encountering monosodium urate (MSU) crystals. Neutrophil extracellular traps (NETs) are found abundantly in the synovial fluid of gout patients. The detailed mechanism of MSU crystal-induced NET formation remains unknown. Our goal was to shed light on possible roles of purinergic signaling and neutrophil migration in mediating NET formation induced by MSU crystals. Interaction of human neutrophils with MSU crystals was evaluated by high-throughput live imaging using confocal microscopy...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27900959/effect-of-vitamin-c-supplementation-on-lipid-profile-serum-uric-acid-and-ascorbic-acid-in-children-on-hemodialysis
#18
Ghada Mohamed El Mashad, Hanan M ElSayed, Nahla A Nosair
Children with end-stage renal disease (ESRD) suffer from dyslipidemia and hyperuricemia that might play a causal role in the progression of cardiovascular disease (CVD). The aim of the study is to assess the effects of Vitamin C supplementation on uric acid, ascorbic acid, and serum lipid levels among children on hemodialysis (HD). This prospective study was conducted in the pediatric nephrology unit at Menoufia University Hospital. The study included a total of 60 children with ESRD on maintenance HD therapy...
November 2016: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/27900275/spinal-gout-a-review-with-case-illustration
#19
Hossein Elgafy, Xiaochen Liu, Joseph Herron
AIM: To summarize clinical presentations and treatment options of spinal gout in the literature from 2000 to 2014, and present theories for possible mechanism of spinal gout formation. METHODS: The authors reviewed 68 published cases of spinal gout, which were collected by searching "spinal gout" on PubMed from 2000 to 2014. The data were analyzed for clinical features, anatomical location of spinal gout, laboratory studies, imaging studies, and treatment choices...
November 18, 2016: World Journal of Orthopedics
https://www.readbyqxmd.com/read/27899376/gwas-of-clinically-defined-gout-and-subtypes-identifies-multiple-susceptibility-loci-that-include-urate-transporter-genes
#20
Akiyoshi Nakayama, Hirofumi Nakaoka, Ken Yamamoto, Masayuki Sakiyama, Amara Shaukat, Yu Toyoda, Yukinori Okada, Yoichiro Kamatani, Takahiro Nakamura, Tappei Takada, Katsuhisa Inoue, Tomoya Yasujima, Hiroaki Yuasa, Yuko Shirahama, Hiroshi Nakashima, Seiko Shimizu, Toshihide Higashino, Yusuke Kawamura, Hiraku Ogata, Makoto Kawaguchi, Yasuyuki Ohkawa, Inaho Danjoh, Atsumi Tokumasu, Keiko Ooyama, Toshimitsu Ito, Takaaki Kondo, Kenji Wakai, Blanka Stiburkova, Karel Pavelka, Lisa K Stamp, Nicola Dalbeth, Yutaka Sakurai, Hiroshi Suzuki, Makoto Hosoyamada, Shin Fujimori, Takashi Yokoo, Tatsuo Hosoya, Ituro Inoue, Atsushi Takahashi, Michiaki Kubo, Hiroshi Ooyama, Toru Shimizu, Kimiyoshi Ichida, Nariyoshi Shinomiya, Tony R Merriman, Hirotaka Matsuo
OBJECTIVE: A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. METHODS: Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zealand Polynesian samples was done to further validate the loci identified in this study...
November 29, 2016: Annals of the Rheumatic Diseases
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