Anti-inflammatory effects of traditional mixed extract of medicinal herbs (MEMH) on monosodium urate crystal-induced gouty arthritis.

PubMed

Nam, Ju-Suk; Jagga, Supriya; Sharma, Ashish Ranjan; Lee, Joon-Hee; Park, Jong Bong; Jung, Jun-Sub; Lee, Sang-Soo

2017-08-01

Korean oriental medicine prescription is widely used for the treatment of gouty diseases. In the present study, we investigated anti-inflammatory effects of modified Korean herbal formulation, mixed extract of medicinal herbs (MEMH), and its modulatory effects on inflammatory mediators associated with gouty arthritis. Both in vitro and in vivo studies were carried out to assess the anti-inflammatory efficacy of MEMH on monosodium urate (MSU) crystals-induced gouty inflammation. MSU crystals stimulated human chondrosarcoma cell line, SW1353, and human primary chondrocytes were treated with MEMH in vitro. The expression levels of pro-inflammatory mediators and metalloproteases were analyzed. The effect of MEMH on NFκB signaling pathway in SW1353 cells was examined. Effect of MEMH on the mRNA expression level of pro-inflammatory mediators and chemotactic factor from human monocytic cell line, THP-1, was also analyzed. The probable role of MEMH in the differentiation process of osteoblast like cells, SaOS-2, after MSU treatment was also observed. To investigate the effects of MEMH in vivo, MSU crystals-induced ankle arthritic model was established. Histopathological changes in affected joints and plasma levels of pro-inflammatory mediators (IL-1β and TNFα) were recorded. MEMH inhibited NFκB signaling pathway and COX-2 protein expression in chondrocytes. MSU-induced mRNA expressions of pro-inflammatory mediators and chemotactic cytokines were suppressed by MEMH. In MSU crystals-induced ankle arthritic mouse model, administration of MEMH relieved inflammatory symptoms and decreased the plasma levels of IL-1β and TNFα. The results indicated that MEMH can effectively inhibit the expression of inflammatory mediators in gouty arthritis, demonstrating its potential for treating gouty arthritis. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Synthesis and characterization of monosodium urate (MSU) nano particles

NASA Astrophysics Data System (ADS)

Tank, Nirali S.; Rathod, K. R.; Parekh, B. B.; Parikh, K. D.; Joshi, M. J.

2016-05-01

In Gout the deposition of crystals of Monosodium Urate (MSU) in various connective tissues and joints occurs, which is very painful with immflamation. The deposition likely to begin with nano particles form and expected to grow in to micro-paricles and hence it is important to synthesize and characrterize MSU nano-particles. The MSU nano particles were synthesized by wet chemical method using NaOH and uric acid (C5H4N4O3) and then characterized by powder XRD, TEM, FT-IR and thermal analysis. From the powder XRD the triclinic structure was found and 40 nm average particle size was estimated by using Scherrer's formula. From TEM the particle size was found to be in the range of 20 to 60 nm. The FT-IR spectrum for the MSU nano particles confirmed the presence of O-H stretching, N-H stretching, N-H rocking, C = O, C = C Enol or Keto and C = N vibrations. The thermal analysis was carried out from room temperature to 900°C. With comparison to the bulk MSU the thermal stability of MSU nano particles was slightly higher and 1.5 water molecules were found to be associated with MSU nano particles. Present results are compared with the bulk MSU.

Monosodium urate crystal deposition associated with the progress of radiographic grade at the sacroiliac joint in axial SpA: a dual-energy CT study.

PubMed

Zhu, Junqing; Li, Aiwu; Jia, Ertao; Zhou, Yi; Xu, Juan; Chen, Shixian; Huang, Yinger; Xiao, Xiang; Li, Juan

2017-05-02

Previous studies have revealed that ankylosing spondylitis (AS), as the progenitor of axial spondyloarthritis (AxSpA), has been characterized by the insidiously progressive nature of sacroiliitis and spondylitis. Dual-energy computed tomography (DECT) has recently been used to analyse the deposition of monosodium urate (MSU) crystals with higher sensitivity and specificity. However, it remains unclear whether the existence of the MSU crystal deposition detected by DECT at the sacroiliac joint in patients with AxSpA also is associated with the existing structural damage. Here, we performed this study to show the DECT MSU crystal deposits in AxSpA patients without coexisting gout and to ascertain the relationship between the MSU crystal deposition and the structural joint damage of sacroiliac joints. One hundred and eighty-six AxSpA patients without coexisting gout were recruited. The plain radiographs of the sacroiliac joint were obtained, along with the DECT scans at the pelvis and the clinical variables. All statistics based on the left or right sacroiliac joint damage grading (0-4) were calculated independently. Bivariate analysis and ordinal logistic regression was performed between the clinical features and radiographic grades at the sacroiliac joint. At the pelvis, large quantities of MSU crystal deposition were found in patients with AxSpA. The average MSU crystal volume at the left sacroiliac joint, the right sacroiliac joint, and the pelvis were 0.902 ± 1.345, 1.074 ± 1.878, and 5.272 ± 9.044 cm 3 , values which were correlated with serum uric acid concentrations (r = 0.727, 0.740, 0.896; p < 0.001). In bivariate analysis, wide clinical variables were associated with the changes in sacroiliac joint damage. Further, the AxSpA duration, BASFI score, and the volume of MSU crystal at both sides of sacroiliac joint were associated with the progress of radiographic grade at the sacroiliac joints in the ordinal logistic models (left AOR = 1.180, 3.800, 1.920; right AOR = 1.190, 3.034, 1.418; p < 0.01). Large quantities of MSU crystal deposition detected by DECT were found at the pelvis in AxSpA patients without coexisting gout. In addition to AxSpA duration and BASFI score, the MSU crystal deposition at the sacroiliac joint is associated with the progress of radiographic grade at sacroiliac joints in those patients.

Effects of RuPeng15 Powder (RPP15) on Monosodium Urate Crystal-Induced Gouty Arthritis in Rats

PubMed Central

Kou, Y.-Y.; Li, Y.-F.; Xu, M.; Li, W.-Y.; Yang, M.; Li, R.-L.

2015-01-01

RuPeng15 Powder (RPP15) is a herbal multicompound remedy that originates from traditional Tibetan medicine and possesses antigout, anti-inflammatory, and antihyperuricemic properties based on the traditional conceptions. The present study was undertaken to evaluate the therapeutic effect of PRP15 in rat gouty arthritis induced by monosodium urate (MSU) crystals. In the present study, we found that treatment with RPP15 (0.4, 0.8, and 1.2 g/kg) in rats with gouty arthritis induced by MSU crystals significantly attenuated the knee swelling. Histomorphometric and immunohistochemistry analyses revealed that MSU-induced inflammatory cell infiltration and the elevated expressions of nuclear transcription factor-κB p65 (NF-κB p65) in synovial tissues were significantly inhibited, and enzyme-linked immunosorbent assay (ELISA) result showed that MSU-induced high levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-8 (IL-8) in synovial fluid were reduced by treatment with RPP15 (0.4, 0.8, and 1.2 g/kg). We conclude that RPP15 may be a promising candidate for the development of a new treatment for gout and its activity of antigout may be partially related to inhibiting TNF-α, IL-1β, IL-8, and NF-κB p65 expression in the synovial tissues. PMID:26221174

Effects of Extract from Mangifera indica Leaf on Monosodium Urate Crystal-Induced Gouty Arthritis in Rats

PubMed Central

Jiang, Yan; You, Xiao-Ying; Fu, Kong-Long; Yin, Wan-Le

2012-01-01

The leaves of Mangifera indica L. (Anacardiaceae) is used as a medicinal material in traditional herb medicine for a long time in India, China, and other Eastern Asian countries. Our present study investigated the therapeutic effects of the ethanol extract from Mangifera indica (EMI) in rat with monosodium urate (MSU) crystals-induced gouty arthritis. Effects of EMI (50, 100, and 200 mg/kg, p.o.) administrated for 9 days on the ankle swelling, synovial tumor necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1β) levels were assessed in MSU crystal rat. Data from our study showed that rat with gouty arthritis induced by MSU crystal demonstrated an elevation in ankle swelling, synovial TNF-α, IL-1β mRNA, and protein levels. Oral administration of 100 and 200 mg/kg EMI for 9 days reversed the abnormalities in ankle swelling, synovial TNF-α, IL-1β mRNA, and protein levels. The results indicated that the beneficial antigouty arthritis effect of EMI may be mediated, at least in part, by inhibiting TNF-α and IL-1β expression in the synovial tissues. Our study suggests that Mangifera indica and its extract may have a considerable potential for development as an anti-gouty arthritis agent for clinical application. PMID:23304232

NALP3 inflammasome functional polymorphisms and gout susceptibility.

PubMed

Miao, Zhi-Min; Zhao, Shi-Hua; Yan, Sheng-Li; Li, Chang-Gui; Wang, Yan-Gang; Meng, Dong-Mei; Zhou, Li; Mi, Qing-Sheng

2009-01-01

Gout is the most common autoinflammatory arthritis characterized by elevated serum urate and recurrent attacks of intra-articular crystal deposition of monosodium urate (MSU). Although the pathogenesis of gout is still unclear, accumulated studies indicate that genetic factors trigger gout development, including some susceptibility genes that control the production and clearance of urate and lead to hyperuricemia. However, the epidemiological evidence suggests that only less than 10% of hyperuricemia patients develop gout, indicating that other genes unrelated to the urate metabolism may also contribute to the diseases susceptibility. Accumulated evidences have implied that MSU crystal-induced inflammation is a paradigm of innate immunity and that NALP3 inflammasome, an innate immune complex containing NALP3, ASC and CARD-8, is involved in gout development. Recent studies suggest that NALP3 and CARD-8 functional mutations contribute to the development of autoinflammatory diseases including hereditary periodic fever syndrome, arthritis as well as hypertension susceptibility. Taking into account these genetic findings, here we would like to propose a novel hypothesis that functional mutations in NALP3 inflammasome may make NALP3 inflammasome as attractive susceptibility candidates and genetic markers for gout. Further clinical genetic studies need to be performed to confirm the role of NALP3 inflammasome in the etiology of gout.

Inhibition of Inducible Nitric Oxide Synthase Attenuates Monosodium Urate-induced Inflammation in Mice

PubMed Central

Ju, Tae-Jin; Dan, Jin-Myoung; Cho, Young-Je

2011-01-01

The present study elucidated the effect of the selective inducible nitric oxide synthase (iNOS) inhibitor N6-(1-iminoethyl)-L-lysine (L-NIL) on monosodium urate (MSU) crystal-induced inflammation and edema in mice feet. L-NIL (5 or 10 mg/kg/day) was administered intraperitoneally 4 h before injection of MSU (4 mg) into the soles of mice hindlimb feet. Twenty-four hours after MSU injection, foot thickness was increased by 160% and L-NIL pretreatment reduced food pad swelling in a dose dependent manner. Pretreatment of 10 mg/kg/day L-NIL significantly suppressed the foot pad swelling by MSU. Plasma level of nitric oxide (NO) metabolites and gene expression and protein level of iNOS in feet were increased by MSU, which was suppressed by L-NIL pretreatment. Similar pattern of change was observed in nitrotyrosine level. MSU increased the gene expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β and L-NIL pretreatment suppressed MSU-induced cytokines expression. The mRNA levels of superoxide dismutase and glutathione peroxidase1 were increased by MSU and L-NIL pretreatment normalized the gene expression. Phosphorylation of extracellular signal-regulated kinase 1/2 and p38 was increased by MSU, which was suppressed by L-NIL pretreatment. The mRNA levels of iNOS, TNF-α, and IL-1β were increased by MSU in human dermal fibroblasts, C2C12 myoblasts, and human fetal osteoblasts in vitro, which was attenuated by L-NIL in a dose dependent manner. This study shows that L-NIL inhibits MSU-induced inflammation and edema in mice feet suggesting that iNOS might be involved in MSU-induced inflammation. PMID:22359474

Beneficial Properties of Phytochemicals on NLRP3 Inflammasome-Mediated Gout and Complication.

PubMed

Jhang, Jhih-Jia; Lin, Jia-Hong; Yen, Gow-Chin

2018-01-31

Gouty arthritis is characterized by the precipitation of monosodium urate (MSU) crystals in the joint. Pro-inflammatory cytokine IL-1β is a critical manifestation in response to MSU crystals attack. IL-1β secretion is dependent on the nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome. Abnormal activation of the NLRP inflammasome is related to cellular oxidative stress. However, recent studies have illustrated that phytochemicals with potent antioxidant activity exert inhibitory effects on NLRP3 inflammasome-mediated diseases. This review focuses on the current findings of studies on the NLRP3 inflammasome and the proposed mechanisms that MSU crystals trigger inflammation via activation of the NLRP3 inflammasome. We also summarized the potential use of phytochemicals on NLRP3 inflammasome-mediated diseases, suggesting that phytochemicals can further prevent acute gout attack.

Joint nociceptor nerve activity and pain in an animal model of acute gout and its modulation by intra-articular hyaluronan

PubMed Central

Marcotti, Aida; Miralles, Ana; Dominguez, Eduardo; Pascual, Eliseo; Gomis, Ana; Belmonte, Carlos; de la Peña, Elvira

2018-01-01

Abstract The mechanisms whereby deposition of monosodium urate (MSU) crystals in gout activates nociceptors to induce joint pain are incompletely understood. We tried to reproduce the signs of painful gouty arthritis, injecting into the knee joint of rats suspensions containing amorphous or triclinic, needle MSU crystals. The magnitude of MSU-induced inflammation and pain behavior signs were correlated with the changes in firing frequency of spontaneous and movement-evoked nerve impulse activity recorded in single knee joint nociceptor saphenous nerve fibers. Joint swelling, mechanical and cold allodynia, and hyperalgesia appeared 3 hours after joint injection of MSU crystals. In parallel, spontaneous and movement-evoked joint nociceptor impulse activity raised significantly. Solutions containing amorphous or needle-shaped MSU crystals had similar inflammatory and electrophysiological effects. Intra-articular injection of hyaluronan (HA, Synvisc), a high-MW glycosaminoglycan present in the synovial fluid with analgesic effects in osteoarthritis, significantly reduced MSU-induced behavioral signs of pain and decreased the enhanced joint nociceptor activity. Our results support the interpretation that pain and nociceptor activation are not triggered by direct mechanical stimulation of nociceptors by MSU crystals, but are primarily caused by the release of excitatory mediators by inflammatory cells activated by MSU crystals. Intra-articular HA decreased behavioral and electrophysiological signs of pain, possibly through its viscoelastic filtering effect on the mechanical forces acting over sensitized joint sensory endings and probably also by a direct interaction of HA molecules with the transducing channels expressed in joint nociceptor terminals. PMID:29319609

Wide-field imaging of birefringent synovial fluid crystals using lens-free polarized microscopy for gout diagnosis

NASA Astrophysics Data System (ADS)

Zhang, Yibo; Lee, Seung Yoon Celine; Zhang, Yun; Furst, Daniel; Fitzgerald, John; Ozcan, Aydogan

2016-06-01

Gout is a form of crystal arthropathy where monosodium urate (MSU) crystals deposit and elicit inflammation in a joint. Diagnosis of gout relies on identification of MSU crystals under a compensated polarized light microscope (CPLM) in synovial fluid aspirated from the patient’s joint. The detection of MSU crystals by optical microscopy is enhanced by their birefringent properties. However, CPLM partially suffers from the high-cost and bulkiness of conventional lens-based microscopy, and its relatively small field-of-view (FOV) limits the efficiency and accuracy of gout diagnosis. Here we present a lens-free polarized microscope which adopts a novel differential and angle-mismatched polarizing optical design achieving wide-field and high-resolution holographic imaging of birefringent objects with a color contrast similar to that of a standard CPLM. The performance of this computational polarization microscope is validated by imaging MSU crystals made from a gout patient’s tophus and steroid crystals used as negative control. This lens-free polarized microscope, with its wide FOV (>20 mm2), cost-effectiveness and field-portability, can significantly improve the efficiency and accuracy of gout diagnosis, reduce costs, and can be deployed even at the point-of-care and in resource-limited clinical settings.

Wide-field imaging of birefringent synovial fluid crystals using lens-free polarized microscopy for gout diagnosis

PubMed Central

Zhang, Yibo; Lee, Seung Yoon Celine; Zhang, Yun; Furst, Daniel; Fitzgerald, John; Ozcan, Aydogan

2016-01-01

Gout is a form of crystal arthropathy where monosodium urate (MSU) crystals deposit and elicit inflammation in a joint. Diagnosis of gout relies on identification of MSU crystals under a compensated polarized light microscope (CPLM) in synovial fluid aspirated from the patient’s joint. The detection of MSU crystals by optical microscopy is enhanced by their birefringent properties. However, CPLM partially suffers from the high-cost and bulkiness of conventional lens-based microscopy, and its relatively small field-of-view (FOV) limits the efficiency and accuracy of gout diagnosis. Here we present a lens-free polarized microscope which adopts a novel differential and angle-mismatched polarizing optical design achieving wide-field and high-resolution holographic imaging of birefringent objects with a color contrast similar to that of a standard CPLM. The performance of this computational polarization microscope is validated by imaging MSU crystals made from a gout patient’s tophus and steroid crystals used as negative control. This lens-free polarized microscope, with its wide FOV (>20 mm2), cost-effectiveness and field-portability, can significantly improve the efficiency and accuracy of gout diagnosis, reduce costs, and can be deployed even at the point-of-care and in resource-limited clinical settings. PMID:27356625

Ultrasonography shows disappearance of monosodium urate crystal deposition on hyaline cartilage after sustained normouricemia is achieved.

PubMed

Thiele, Ralf G; Schlesinger, Naomi

2010-02-01

This study aimed at determining whether lowering serum urate (SU) to less than 6 mg/dl in patients with gout affects ultrasonographic findings. Seven joints in five patients with monosodium urate (MSU) crystal proven gout and hyperuricemia were examined over time with serial ultrasonography. Four of the five patients were treated with urate lowering drugs (ULDs) (allopurinol, n = 3; probenecid, n = 1). One patient was treated with colchicine alone. Attention was given to changes in a hyperechoic, irregular coating of the hyaline cartilage in the examined joints (double contour sign or "urate icing"). This coating was considered to represent precipitate of MSU crystals. Index joints included metacarpophalangeal (MCP) joints (n = 2), knee joints (n = 3), and first metatarsophalangeal (MTP) joints (n = 2). The interval between baseline and follow-up images ranged from 7 to 18 months. Serial SU levels were obtained during the follow-up period. During the follow-up period, three patients treated with ULD (allopurinol, n = 2; probenecid, n = 1) achieved a SU level of <6 mg/dl. In two patients, SU levels remained above 6 mg/dl (treated with allopurinol, n = 1; treated with colchicine, n = 1). At baseline, the double contour sign was seen in all patients. In those patients who achieved SU levels of <6 ml/dl, this sign had disappeared at follow-up. Disappearance of the double contour sign was seen in two knee joints, two first MTP joints, and one MCP joint. In contrast, disappearance of the double contour sign was not seen in patients who maintained a SU level > or =7 mg/dl. In one patient treated with allopurinol, SU levels improved from 13 to 7 mg/dl during the follow-up period. Decrease, but not resolution of the hyperechoic coating was seen in this patient. In the patient treated with colchicine alone, SU levels remained >8 mg/dl, and no sonographic change was observed. In our patients, sonographic signs of deposition of MSU crystals on the surface of hyaline cartilage disappeared completely if sustained normouricemia was achieved. This is the first report showing that characteristic sonographic changes are influenced by ULDs once SU levels remain < or =6 mg/dl for 7 months or more. Sonographic changes of gout correlate with SU levels and may be a non-invasive means to track changes in the uric acid pool. Larger prospective studies are needed to further assess these potentially important findings.

Berberine, an isoquinoline alkaloid suppresses TXNIP mediated NLRP3 inflammasome activation in MSU crystal stimulated RAW 264.7 macrophages through the upregulation of Nrf2 transcription factor and alleviates MSU crystal induced inflammation in rats.

PubMed

Dinesh, Palani; Rasool, MahaboobKhan

2017-03-01

The current study was designed to investigate the therapeutic potential of berberine on monosodium urate (MSU) crystal stimulated RAW 264.7 macrophages and in MSU crystal induced rats. Our results indicate that berberine (25, 50 and 75μM) suppressed the levels of pro-inflammatory cytokines (interleukin-1beta (IL-1β) and tumor necrosis factor alpha (TNFα)) and intracellular reactive oxygen species in MSU crystal stimulated RAW 264.7 macrophages. The mRNA expression levels of IL-1β, caspase 1, nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3), thioredoxin interacting protein (TXNIP) and kelch-like ECH-associated protein 1 (Keap1) were found downregulated with the upregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) transcription factor and its associated anti-oxidant enzymes: Heme oxygenase I (HO-1), superoxide dismutase (SOD1), glutathione peroxidase (GPx), NADPH quinone oxidoreductase-1 (NQO1) and catalase (CAT) in MSU crystal stimulated RAW 264.7 macrophages upon berberine treatment. Subsequently, western blot analysis revealed that berberine decreased the protein expression of IL-1β and caspase 1 and increased Nrf2 expression in RAW 264.7 macrophages. Immunofluorescence analysis also explored increased expression of Nrf2 in MSU crystal stimulated RAW 264.7 macrophages by berberine treatment. In addition, the paw edema, pain score, pro-inflammatory cytokines (IL-1β and TNFα) and articular elastase activity were found significantly reduced in berberine (50mg/kgb·wt) administered MSU crystal-induced rats. Conclusively, our current findings suggest that berberine may represent as a potential candidate for the treatment of gouty arthritis by suppressing inflammatory mediators and activating Nrf2 anti-oxidant pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

Ultrasound scans and dual energy CT identify tendons as preferred anatomical location of MSU crystal depositions in gouty joints.

PubMed

Yuan, Yuan; Liu, Chang; Xiang, Xi; Yuan, Tong-Ling; Qiu, Li; Liu, Yi; Luo, Yu-Bin; Zhao, Y; Herrmann, Martin

2018-05-01

The present study was performed to localize the articular deposition of monosodium urate (MSU) crystal in joints. We compare the detection efficiencies of dual-energy CT (DECT) and ultrasound scans. Analyses by DECT and ultrasound were performed with 184 bilateral joints of the lower limbs of 54 consecutive gout patients. All joints were categorized into (1) knee, (2) ankle, (3) MTP1, and (4) MTP2, and sorted into those with and those without detectable MSU deposition. The comparison of the positive rate between DECT and ultrasound and the agreement was performed using the McNemar test and the Cohen's κ coefficient, respectively. Next, we listed the MSU crystal deposition as assessed by ultrasound between the DECT-positive and -negative joints according to their interior structure. We included tendons, synovia, cartilage, subcutaneous tissue, etc. RESULTS: Among all joints, the percentages with MSU crystal deposition detected by DECT (99/184, 53.8%) and ultrasound (106/184, 57.6%) were comparable (P = 0.530 > 0.05). For MTP1 (21/34, 61.8%; 12/34, 35.3%; P < 0.05) and MTP2-5 (17/34, 50.0%; 10/34, 29.4%, P < 0.05), ultrasound and DECT were more efficient, respectively. The data concordance in 46 of 50 joints (92.00%; κ = 0.769, P < 0.05) for knee; and 27 of 34 joints (79.41%; κ = 0.588, P < 0.05) for MTP2-5 and suggested that tendons were the most frequent anatomical location of MSU crystal deposition. The tendons are the most frequent anatomical location of MSU crystal depositions. The concordance rate of knee joints and MTP2-5 joints shows good agreement between DECT and ultrasound depending on the location.

2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative

PubMed Central

Neogi, Tuhina; Jansen, Tim L Th A; Dalbeth, Nicola; Fransen, Jaap; Schumacher, H Ralph; Berendsen, Dianne; Brown, Melanie; Choi, Hyon; Edwards, N Lawrence; Janssens, Hein J E M; Lioté, Frédéric; Naden, Raymond P; Nuki, George; Ogdie, Alexis; Perez-Ruiz, Fernando; Saag, Kenneth; Singh, Jasvinder A; Sundy, John S; Tausche, Anne-Kathrin; Vaquez-Mellado, Janitzia; Yarows, Steven A; Taylor, William J

2015-01-01

Objective Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout. Methods An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multi-criterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set. Results The entry criterion for the new classification criteria requires the occurrence of at least one episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (ie, synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU-negative synovial fluid aspirate), and imaging (double-contour sign on ultrasound or urate on dual-energy CT, radiographic gout-related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively). Conclusions The new classification criteria, developed using a data-driven and decision-analytic approach, have excellent performance characteristics and incorporate current state-of-the-art evidence regarding gout. PMID:26359487

Uric acid as a danger signal in gout and its comorbidities

PubMed Central

Rock, Kenneth L.; Kataoka, Hiroshi; Lai, Jiann-Jyh

2013-01-01

Uric acid is a waste product of purine catabolism. This molecule comes to clinical attention when it nucleates to form crystals of monosodium urate (MSU) in joints or other tissues and thereby causes the inflammatory disease of gout. Patients with gout also frequently suffer from a number of co-morbid conditions including hypertension, diabetes mellitus and cardiovascular disease. Why MSU crystals trigger inflammation and are associated with comorbidities of gout has been unclear, but recent studies provide new insights these issues. Rather than simply being a waste product, uric acid could serve a pathophysiological role as a local alarm signal that alerts the immune system to cell injury and helps to trigger both innate and adaptive immune responses. The inflammatory component of these immune responses is caused when urate crystals trigger both inflammasome-dependent and independent pathways to generate the proinflammatory cytokine IL-1. The resulting bioactive IL-1 stimulates the inflammation of gout and might contribute to the development of other comorbidities. Surprisingly, the same mechanisms underlie the inflammatory response to a number of irritant particles, many of which also cause disease. These new insights help to explain the pathogenesis of gout and point to potential new therapeutic targets for this and other sterile inflammatory diseases. PMID:22945591

Targeting inflammatory mediators with ferulic acid, a dietary polyphenol, for the suppression of monosodium urate crystal-induced inflammation in rats.

PubMed

Doss, Hari Madhuri; Dey, Chandrima; Sudandiradoss, C; Rasool, Mahaboob Khan

2016-03-01

The aim of this study was to investigate the anti-inflammatory effect of ferulic acid, a dietary phenol, on monosodium urate (MSU) crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. For the purpose of comparison, colchicine was used as a reference drug. Paw edema, levels/activities of elastase, lysosomal enzymes (acid phosphatase and β-galactosidase), nitric oxide, lipid peroxidation, antioxidant status and pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β), and histology of ankle joints were evaluated in rats with MSU crystal-induced inflammation. The messenger RNA (mRNA) expression of pro-inflammatory cytokines (TNF-α and IL-1β), NLRP3 (nucleotide oligomerization domain (NOD)-like receptor family, pyrin domain containing 3) inflammasomes, caspase-1, and the transcription factor nuclear factor kappa B p65 (NF-κB p65) was determined by real-time polymerase chain reaction (PCR) analysis. The protein expression of NF-κB p65 and TNF-α was detected by immunohistochemical analysis. Further, a molecular docking analysis was conducted to determine the ligand efficiency of ferulic acid towards NF-κB, apoptosis-associated speck-like protein containing a CARD (PYCARD/ASC), NLRP3, and pro-caspase-1. In the joint homogenate of rats with MSU crystal-induced inflammation, treatment with ferulic acid (30mg/kg body weight (b.wt)) decreased paw edema; the level/activity of elastase, lysosomal enzymes, nitric oxide, lipid peroxidation, and pro-inflammatory cytokines (TNF-α and IL-1β); and the mRNA expression of NLRP3 inflammasomes, caspase-1, pro-inflammatory cytokines, and NF-κB p65. In addition, the protein expression of NF-κB p65 and TNF-α was also found to be significantly decreased. However, the antioxidant status (superoxide dismutase (SOD) and catalase (CAT)) were found to be increased. The molecular docking analysis showed that ferulic acid exhibited significant ligand efficiency towards pro-caspase-1, NF-κB, PYCARD/ASC, and NLRP3. Our findings demonstrate the potential anti-inflammatory effect of ferulic acid on MSU crystal-induced inflammation in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Interleukin 37 limits monosodium urate crystal-induced innate immune responses in human and murine models of gout.

PubMed

Liu, Lei; Xue, Yu; Zhu, Yingfeng; Xuan, Dandan; Yang, Xue; Liang, Minrui; Wang, Juan; Zhu, Xiaoxia; Zhang, Jiong; Zou, Hejian

2016-11-18

Interleukin (IL)-37 has emerged as a fundamental inhibitor of innate immunity. Acute gout is a self-limiting inflammatory response to monosodium urate (MSU) crystals. In the current study, we assessed the preventive and therapeutic effect of recombinant human IL-37 (rhIL-37) in human and murine gout models. We investigated the expression of IL-37 in patients with active and inactive gouty arthritis and assessed the effect of rhIL-37 in human and murine gout models: a human monocyte cell line (THP-1) and human synovial cells (containing macrophage-like and fibroblast-like synoviocytes) exposed to MSU crystals, a peritoneal murine model of gout and a murine gouty arthritis model. After inhibition of Mer receptor tyrosine kinase (Mertk), levels of IL-1β, IL-8 and chemokine (C-C motif) ligand 2 (CCL-2) were detected by ELISA and expression of mammalian homologs of the drosophila Mad gene 3 (Smad), suppressor of cytokine signaling 3 (SOCS3), NACHT-LRR-PYD-containing protein 3 (NLRP3), and IL-8R of THP-1 were assessed by qPCR and western blot to explore the molecular mechanisms. Our studies strongly indicated that rhIL-37 played a potent immunosuppressive role in the pathogenesis of experimental gout models both in vitro and in vivo, by downregulating proinflammatory cytokines and chemokines, markedly reducing neutrophil and monocyte recruitment, and mitigating pathological joint inflammation. In our studies, rhIL-37 suppressed MSU-induced innate immune responses by enhancing expression of Smad3 and IL-1R8 to trigger multiple intracellular switches to block inflammation, including inhibition of NLRP3 and activation of SOCS3. Mertk signaling participated in rhIL-37 inhibitory pathways in gout models. By inhibition of Mertk, the anti-inflammatory effect of rhIL-37 was partly abrogated, and IL-1R8, Smad3 and S​OCS3 expression were suppressed, whereas NLRP3 expression was reactivated. Our studies reveal that IL-37 limits runaway inflammation initiated by MSU crystal-induced immune responses, partly in a Mertk-dependent fashion. Thus, rhIL-37 has both preventive and therapeutic effects in gouty arthritis.

Presence of Gout is Associated With Increased Prevalence and Severity of Knee Osteoarthritis

PubMed Central

Howard, Rennie G.; Samuels, Jonathan; Gyftopoulos, Soterios; Krasnokutsky, Svetlana; Leung, Joseph; Swearingen, Christopher J.; Pillinger, Michael H.

2015-01-01

Background Gout and osteoarthritis (OA) are the most prevalent arthritides, but their relationship is neither well established nor well understood. Objectives We assessed whether a diagnosis of gout or asymptomatic hyperuricemia (AH) is associated with increased prevalence/severity of knee OA. Methods 119 male patients ages 55–85 were sequentially enrolled from the primary care clinics of an urban VA hospital, assessed and categorized into 3 groups: gout (ACR Classification Criteria), AH ([serum urate] ≥ 6.8 mg/dL, no gout), and control ([serum urate] < 6.8 mg/dL, no gout). 25 patients from each group subsequently underwent formal assessment of knee OA presence and severity (ACR Clinical/Radiographic Criteria, Kellgren-Lawrence (KL) grade). Musculoskeletal ultrasound was used to detect monosodium urate (MSU) deposition at the knees and 1st metatarsophalangeal (MTP) joints. Results 68.0% of gout, 52.0% of AH, and 28.0% of age-matched control subjects had knee OA (gout vs. control, P=0.017). Odds ratio for knee OA in gout vs. controls was 5.46 prior to, and 3.80 after adjusting for BMI. Gout subjects also had higher KL grades than controls (P=0.001). Subjects with sonographically-detected MSU crystal deposition on cartilage were more likely to have OA than those without (60.0 vs 27.5%, P=0.037), with crystal deposition at the 1st MTP joints correlating most closely with OA knee involvement. Conclusion Knee OA was more prevalent in gout patients vs. controls, and intermediate in AH. Knee OA was more severe in gout patients vs. controls. PMID:25710856

Blocking fatty acid-fueled mROS production within macrophages alleviates acute gouty inflammation.

PubMed

Hall, Christopher J; Sanderson, Leslie E; Lawrence, Lisa M; Pool, Bregina; van der Kroef, Maarten; Ashimbayeva, Elina; Britto, Denver; Harper, Jacquie L; Lieschke, Graham J; Astin, Jonathan W; Crosier, Kathryn E; Dalbeth, Nicola; Crosier, Philip S

2018-05-01

Gout is the most common inflammatory arthritis affecting men. Acute gouty inflammation is triggered by monosodium urate (MSU) crystal deposition in and around joints that activates macrophages into a proinflammatory state, resulting in neutrophil recruitment. A complete understanding of how MSU crystals activate macrophages in vivo has been difficult because of limitations of live imaging this process in traditional animal models. By live imaging the macrophage and neutrophil response to MSU crystals within an intact host (larval zebrafish), we reveal that macrophage activation requires mitochondrial ROS (mROS) generated through fatty acid oxidation. This mitochondrial source of ROS contributes to NF-κB-driven production of IL-1β and TNF-α, which promote neutrophil recruitment. We demonstrate the therapeutic utility of this discovery by showing that this mechanism is conserved in human macrophages and, via pharmacologic blockade, that it contributes to neutrophil recruitment in a mouse model of acute gouty inflammation. To our knowledge, this study is the first to uncover an immunometabolic mechanism of macrophage activation that operates during acute gouty inflammation. Targeting this pathway holds promise in the management of gout and, potentially, other macrophage-driven diseases.

2015 Gout Classification Criteria: An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative

PubMed Central

Jansen, Tim L. Th. A.; Dalbeth, Nicola; Fransen, Jaap; Schumacher, H. Ralph; Berendsen, Dianne; Brown, Melanie; Choi, Hyon; Edwards, N. Lawrence; Janssens, Hein J. E. M.; Lioté, Frédéric; Naden, Raymond P.; Nuki, George; Ogdie, Alexis; Perez‐Ruiz, Fernando; Saag, Kenneth; Singh, Jasvinder A.; Sundy, John S.; Tausche, Anne‐Kathrin; Vaquez‐Mellado, Janitzia; Yarows, Steven A.; Taylor, William J.

2015-01-01

Objective Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout. Methods An international group of investigators, supported by the American College of Rheumatology and the European League Against Rheumatism, conducted a systematic review of the literature on advanced imaging of gout, a diagnostic study in which the presence of monosodium urate monohydrate (MSU) crystals in synovial fluid or tophus was the gold standard, a ranking exercise of paper patient cases, and a multicriterion decision analysis exercise. These data formed the basis for developing the classification criteria, which were tested in an independent data set. Results The entry criterion for the new classification criteria requires the occurrence of at least 1 episode of peripheral joint or bursal swelling, pain, or tenderness. The presence of MSU crystals in a symptomatic joint/bursa (i.e., synovial fluid) or in a tophus is a sufficient criterion for classification of the subject as having gout, and does not require further scoring. The domains of the new classification criteria include clinical (pattern of joint/bursa involvement, characteristics and time course of symptomatic episodes), laboratory (serum urate, MSU‐negative synovial fluid aspirate), and imaging (double‐contour sign on ultrasound or urate on dual‐energy computed tomography, radiographic gout‐related erosion). The sensitivity and specificity of the criteria are high (92% and 89%, respectively). Conclusion The new classification criteria, developed using a data‐driven and decision analytic approach, have excellent performance characteristics and incorporate current state‐of‐the‐art evidence regarding gout. PMID:26352873

Gout.

PubMed

Pascual, Eliseo; Pedraz, Teresa

2004-05-01

We have reviewed the latest publications on epidemiology of gout; also there have been new insights into the regulation of the inflammation resulting from the regular interaction occurring between MSU crystals and cells in both asymptomatic and symptomatic gouty joints. Finally we review different publications of clinical interest. The incidence of gout has been found to be increasing, and the disease starts at an earlier age; this likely relates to changes in dietary habits that lead to the development of the insulin resistance syndrome to which hyperuricemia, and thus gout, relates. Dietary modifications to correct the insulin resistance syndrome and reduce uricemia by increasing renal clearance of urate have heath consequences that go far beyond their beneficial effect on gout. Monosodium urate crystals and cells interact in the asymptomatic joints of gouty patients. The mechanisms that trigger a gouty attack with this background and those responsible for the self-limitation of gouty attacks are not understood. The degree of maturation of the monocytes-macrophages present in the fluid appears to modulate the consequences of the crystal-cell interaction and gives a hint of how from the crystal-cell interaction may result in such divergent consequences as intense inflammation or the absence of symptoms. Interest in gout treatment continues, as shown by the number of papers on the subject reviewed. In most cases, gout is an easy disease to treat, but we do not have enough information about how to handle those few patients with "difficult" disease, and what we refer colloquially to as difficult gout has not been properly defined yet. Gout incidence and severity appear to be increasing likely in relation to dietary habits. Switching the pattern of secretion of inflammatory mediators with maturating macrophages which contain MSU crystals may be the key to self limitation of gouty attacks. We must define better which gout is a "difficult" one.

Anti-inflammatory and antinociceptive effects of Chinese medicine SQ gout capsules and its modulation of pro-inflammatory cytokines focusing on gout arthritis.

PubMed

Kodithuwakku, Nandani Darshika; Pan, Min; Zhu, Yi-lin; Zhang, Yan-yan; Feng, Yi-dong; Fang, Wei-rong; Li, Yun-man

2013-12-12

Shuang-Qi gout capsule is a traditional Chinese medicine prescription, which has been used in the treatment of joint pain, inflammation and gout arthritis. This study evaluates anti-inflammatory and antinociceptive effects of Shuang-Qi gout capsule and its modulation of pro-inflammatory cytokines with special reference to gout arthritis. Anti-inflammatory effect of Shuang-Qi gout capsule was investigated bymice tail-flick response, acetic acid induced writhing response, Xylene-induced auricle inflammation and the hind paw volume of the monosodium urate (MSU) crystal induced rats with different time durations. To investigate the effects on gout arthritis, ankle joint of rats induced by MSU crystals and assessed for edema and histopathological changes. In vitro, prepared serum was incubated with urate crystal induced HUVE cells and the release of TNF-α and IL-1β determined by ELISA. Shuang-Qi gout capsule showed significant and dose dependent anti-inflammatory effect via reducing edema and pain, throughout all the models. The high dose of Shuang-Qi gout capsule and Indomethacin significantly attenuated the edema. Histopathological results showed that high and medium dose of Shuang-Qi gout capsule and Indomethacin reduced gouty joint inflammatory features, while the high dose of Shuang-Qi gout capsule showed a better therapeutic effect. High and medium dose of Shuang-Qi gout capsule significantly reduced the release of TNF-α and IL-1β (p<0.05). Shuang-Qi gout capsule can effectively inhibit the inflammation, analgesia, through the modulation of emission of pro-inflammatory cytokines and the curative effect is dose dependent. Conversely, these MSU induced in vivo and in vitro studies of Shuang-Qi gout capsule suggest that, Shuang-Qi gout capsule may be a potential agent for treatment in gouty arthritis. © 2013 Published by Elsevier Ireland Ltd.

Wide-field synovial fluid imaging using polarized lens-free on-chip microscopy for point-of-care diagnostics of gout (Conference Presentation)

NASA Astrophysics Data System (ADS)

Zhang, Yibo; Lee, Seung Yoon; Zhang, Yun; Furst, Daniel; Fitzgerald, John; Ozcan, Aydogan

2016-03-01

Gout and pseudogout are forms of crystal arthropathy caused by monosodium urate (MSU) and calcium pyrophosphate dehydrate (CPPD) crystals in the joint, respectively, that can result in painful joints. Detecting the unique-shaped, birefringent MSU/CPPD crystals in a synovial fluid sample using a compensated polarizing microscope has been the gold-standard for diagnosis since the 1960's. However, this can be time-consuming and inaccurate, especially if there are only few crystals in the fluid. The high-cost and bulkiness of conventional microscopes can also be limiting for point-of-care diagnosis. Lens-free on-chip microscopy based on digital holography routinely achieves high-throughput and high-resolution imaging in a cost-effective and field-portable design. Here we demonstrate, for the first time, polarized lens-free on-chip imaging of MSU and CPPD crystals over a wide field-of-view (FOV ~ 20.5 mm2, i.e., <20-fold larger compared a typical 20X objective-lens FOV) for point-of-care diagnostics of gout and pseudogout. Circularly polarizer partially-coherent light is used to illuminate the synovial fluid sample on a glass slide, after which a quarter-wave-plate and an angle-mismatched linear polarizer are used to analyze the transmitted light. Two lens-free holograms of the MSU/CPPD sample are taken, with the sample rotated by 90°, to rule out any non-birefringent objects within the specimen. A phase-recovery algorithm is also used to improve the reconstruction quality, and digital pseudo-coloring is utilized to match the color and contrast of the lens-free image to that of a gold-standard microscope image to ease the examination by a rheumatologist or a laboratory technician, and to facilitate computerized analysis.

Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury

PubMed Central

Maejima, Ikuko; Takahashi, Atsushi; Omori, Hiroko; Kimura, Tomonori; Takabatake, Yoshitsugu; Saitoh, Tatsuya; Yamamoto, Akitsugu; Hamasaki, Maho; Noda, Takeshi; Isaka, Yoshitaka; Yoshimori, Tamotsu

2013-01-01

Diverse causes, including pathogenic invasion or the uptake of mineral crystals such as silica and monosodium urate (MSU), threaten cells with lysosomal rupture, which can lead to oxidative stress, inflammation, and apoptosis or necrosis. Here, we demonstrate that lysosomes are selectively sequestered by autophagy, when damaged by MSU, silica, or the lysosomotropic reagent L-Leucyl-L-leucine methyl ester (LLOMe). Autophagic machinery is recruited only on damaged lysosomes, which are then engulfed by autophagosomes. In an autophagy-dependent manner, low pH and degradation capacity of damaged lysosomes are recovered. Under conditions of lysosomal damage, loss of autophagy causes inhibition of lysosomal biogenesis in vitro and deterioration of acute kidney injury in vivo. Thus, we propose that sequestration of damaged lysosomes by autophagy is indispensable for cellular and tissue homeostasis. PMID:23921551

Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury.

PubMed

Maejima, Ikuko; Takahashi, Atsushi; Omori, Hiroko; Kimura, Tomonori; Takabatake, Yoshitsugu; Saitoh, Tatsuya; Yamamoto, Akitsugu; Hamasaki, Maho; Noda, Takeshi; Isaka, Yoshitaka; Yoshimori, Tamotsu

2013-08-28

Diverse causes, including pathogenic invasion or the uptake of mineral crystals such as silica and monosodium urate (MSU), threaten cells with lysosomal rupture, which can lead to oxidative stress, inflammation, and apoptosis or necrosis. Here, we demonstrate that lysosomes are selectively sequestered by autophagy, when damaged by MSU, silica, or the lysosomotropic reagent L-Leucyl-L-leucine methyl ester (LLOMe). Autophagic machinery is recruited only on damaged lysosomes, which are then engulfed by autophagosomes. In an autophagy-dependent manner, low pH and degradation capacity of damaged lysosomes are recovered. Under conditions of lysosomal damage, loss of autophagy causes inhibition of lysosomal biogenesis in vitro and deterioration of acute kidney injury in vivo. Thus, we propose that sequestration of damaged lysosomes by autophagy is indispensable for cellular and tissue homeostasis.

Role of Dual Energy Computed Tomography Imaging in the Diagnosis of Gout

PubMed Central

Sehra, Shiv T; Anand, Suneesh; Stallings, Gary W.; Danve, Abhijeet

2017-01-01

Gout is a well-known inflammatory arthritis and affects four percent of the United States population. It results from the deposition of uric acid crystals in joints, tendons, bursae, and other surrounding tissues. Prevalence of gout has increased in the recent decade. Gout is usually seen in conjunction with other chronic comorbid conditions like cardiac disease, metabolic syndrome, and renal disease. The diagnosis of this inflammatory arthritis is confirmed by visualization of monosodium urate (MSU) crystals in the synovial fluid. Though synovial fluid aspiration is the standard of care, it is often deferred because of inaccessibility of small joints, patient assessment during intercritical period, or procedural inexperience in a primary care office. Dual energy computed tomography (DECT) is a relatively new imaging modality which shows great promise in the diagnosis of gout. It is a good noninvasive alternative to synovial fluid aspiration. DECT is increasingly useful in diagnosing cases of gout where synovial fluid fails to demonstrate monosodium urate crystals. In this article, we will review the mechanism, types, advantages, and disadvantages of DECT. PMID:28229032

Feasibility of a tetracycline-binding method for detecting synovial fluid basic calcium phosphate crystals.

PubMed

Rosenthal, Ann K; Fahey, Mark; Gohr, Claudia; Burner, Todd; Konon, Irina; Daft, Laureen; Mattson, Eric; Hirschmugl, Carol; Ryan, Lawrence M; Simkin, Peter

2008-10-01

Basic calcium phosphate (BCP) crystals are common components of osteoarthritis (OA) synovial fluid. Progress in understanding the role of these bioactive particles in clinical OA has been hampered by difficulties in their identification. Tetracyclines stain calcium phosphate mineral in bone. The aim of this study was to investigate whether tetracycline staining might be an additional or alternative method for identifying BCP crystals in synovial fluid. A drop of oxytetracycline was mixed with a drop of fluid containing synthetic or native BCP, calcium pyrophosphate dihydrate (CPPD), or monosodium urate (MSU) crystals and placed on a microscope slide. Stained and unstained crystals were examined by light microscopy, with and without a portable broad-spectrum ultraviolet (UV) pen light. A small set of characterized synovial fluid samples were compared by staining with alizarin red S and oxytetracycline. Synthetic BCP crystals in synovial fluid were quantified fluorimetrically using oxytetracycline. After oxytetracycline staining, synthetic and native BCP crystals appeared as fluorescent amorphous aggregates under UV light. Oxytetracycline did not stain CPPD or MSU crystals or other particulates. Oxytetracycline staining had fewer false-positive test results than did alizarin red S staining and could provide estimates of the quantities of synthetic BCP crystals in synovial fluid. With further validation, oxytetracycline staining may prove to be a useful adjunct or alternative to currently available methods for identifying BCP crystals in synovial fluid.

Uric acid priming in human monocytes is driven by the AKT-PRAS40 autophagy pathway.

PubMed

Crişan, Tania O; Cleophas, Maartje C P; Novakovic, Boris; Erler, Kathrin; van de Veerdonk, Frank L; Stunnenberg, Hendrik G; Netea, Mihai G; Dinarello, Charles A; Joosten, Leo A B

2017-05-23

Metabolic triggers are important inducers of the inflammatory processes in gout. Whereas the high serum urate levels observed in patients with gout predispose them to the formation of monosodium urate (MSU) crystals, soluble urate also primes for inflammatory signals in cells responding to gout-related stimuli, but also in other common metabolic diseases. In this study, we investigated the mechanisms through which uric acid selectively lowers human blood monocyte production of the natural inhibitor IL-1 receptor antagonist (IL-1Ra) and shifts production toward the highly inflammatory IL-1β. Monocytes from healthy volunteers were first primed with uric acid for 24 h and then subjected to stimulation with lipopolysaccharide (LPS) in the presence or absence of MSU. Transcriptomic analysis revealed broad inflammatory pathways associated with uric acid priming, with NF-κB and mammalian target of rapamycin (mTOR) signaling strongly increased. Functional validation did not identify NF-κB or AMP-activated protein kinase phosphorylation, but uric acid priming induced phosphorylation of AKT and proline-rich AKT substrate 40 kDa (PRAS 40), which in turn activated mTOR. Subsequently, Western blot for the autophagic structure LC3-I and LC3-II (microtubule-associated protein 1A/1B-light chain 3) fractions, as well as fluorescence microscopy of LC3-GFP-overexpressing HeLa cells, revealed lower autophagic activity in cells exposed to uric acid compared with control conditions. Interestingly, reactive oxygen species production was diminished by uric acid priming. Thus, the Akt-PRAS40 pathway is activated by uric acid, which inhibits autophagy and recapitulates the uric acid-induced proinflammatory cytokine phenotype.

Uric acid priming in human monocytes is driven by the AKT–PRAS40 autophagy pathway

PubMed Central

Crişan, Tania O.; Cleophas, Maartje C. P.; Novakovic, Boris; Erler, Kathrin; van de Veerdonk, Frank L.; Stunnenberg, Hendrik G.; Netea, Mihai G.; Dinarello, Charles A.; Joosten, Leo A. B.

2017-01-01

Metabolic triggers are important inducers of the inflammatory processes in gout. Whereas the high serum urate levels observed in patients with gout predispose them to the formation of monosodium urate (MSU) crystals, soluble urate also primes for inflammatory signals in cells responding to gout-related stimuli, but also in other common metabolic diseases. In this study, we investigated the mechanisms through which uric acid selectively lowers human blood monocyte production of the natural inhibitor IL-1 receptor antagonist (IL-1Ra) and shifts production toward the highly inflammatory IL-1β. Monocytes from healthy volunteers were first primed with uric acid for 24 h and then subjected to stimulation with lipopolysaccharide (LPS) in the presence or absence of MSU. Transcriptomic analysis revealed broad inflammatory pathways associated with uric acid priming, with NF-κB and mammalian target of rapamycin (mTOR) signaling strongly increased. Functional validation did not identify NF-κB or AMP-activated protein kinase phosphorylation, but uric acid priming induced phosphorylation of AKT and proline-rich AKT substrate 40 kDa (PRAS 40), which in turn activated mTOR. Subsequently, Western blot for the autophagic structure LC3-I and LC3-II (microtubule-associated protein 1A/1B-light chain 3) fractions, as well as fluorescence microscopy of LC3-GFP–overexpressing HeLa cells, revealed lower autophagic activity in cells exposed to uric acid compared with control conditions. Interestingly, reactive oxygen species production was diminished by uric acid priming. Thus, the Akt–PRAS40 pathway is activated by uric acid, which inhibits autophagy and recapitulates the uric acid-induced proinflammatory cytokine phenotype. PMID:28484006

Effects of the Aqueous Extract from Tabebuia roseoalba and Phenolic Acids on Hyperuricemia and Inflammation

PubMed Central

Ferraz-Filha, Zilma Schimith; Ferrari, Fernanda Cristina; Araújo, Marcela Carolina de Paula Michel; Bernardes, Ana Catharina Fernandes P. F.

2017-01-01

Tabebuia species (Bignoniaceae) have long been used in folk medicine as anti-inflammatory, antirheumatic, antimicrobial, and antitumor. The aim of this study was to investigate if aqueous extract from the leaves (AEL) of Tabebuia roseoalba (Ridl.) Sandwith, Bignoniaceae, and its constituents could be useful to decrease serum uric acid levels and restrain the gout inflammatory process. HPLC analysis identified caffeic acid and chlorogenic acid in AEL. Antihyperuricemic effects and inhibition of liver XOD (xanthine oxidoreductase) by AEL and identified compounds were evaluated in hyperuricemic mice. Anti-inflammatory activity was evaluated on MSU (monosodium urate) crystal-induced paw edema. In addition, AEL antioxidant activity in vitro was evaluated. AEL, caffeic, and chlorogenic acids were able to reduce serum uric acid levels in hyperuricemic mice probably through inhibition of liver xanthine oxidase activity and significantly decreased the paw edema induced by MSU crystals. AEL showed significant antioxidant activity in all evaluated assays. The results show that the AEL of Tabebuia roseoalba can be a promising agent for treatment for gout and inflammatory diseases. We suggest that caffeic and chlorogenic acids may be responsible for the activities demonstrated by the species. PMID:29375639

Uric Acid, Hyperuricemia and Vascular Diseases

PubMed Central

Jin, Ming; Yang, Fan; Yang, Irene; Yin, Ying; Luo, Jin Jun; Wang, Hong; Yang, Xiao-Feng

2011-01-01

Uric acid is the product of purine metabolism. It is known that hyperuricemia, defined as high levels of blood uric acid, is the major etiological factor of gout. A number of epidemiological reports have increasingly linked hyperuricemia with cardiovascular and neurological diseases. Studies highlighting the pathogenic mechanisms of uric acid point to an inflammatory response as the primary mechanism for inducing gout and possibly contributing to uric acid's vascular effects. Monosodium urate (MSU) crystals induce an inflammatory reaction, which are recognized by Toll-like receptors (TLRs). These TLRs then activate NALP3 inflammasome. MSU also triggers neutrophil activation and further produces immune mediators, which lead to a proinflammatory response. In addition, soluble uric acid can also mediate the generation of free radicals and function as a pro-oxidant. This review summarizes the epidemiological studies of hyperuricemia and cardiovascular disease, takes a brief look at hyperuricemia and its role in neurological diseases, and highlights the studies of the advanced pathological mechanisms of uric acid and inflammation. PMID:22201767

Diagnosis of chronic gout: evaluating the american college of rheumatology proposal, European league against rheumatism recommendations, and clinical judgment.

PubMed

Peláez-Ballestas, Ingris; Hernández Cuevas, Claudia; Burgos-Vargas, Rubén; Hernández Roque, Lizandra; Terán, Leobardo; Espinoza, Jesús; Esquivel-Valerio, Jorge A; Goycochea-Robles, María Victoria; Aceves, Francisco J; Bernard, Ana Guilaisne; Ventura, Lucio; Shumsky, Clara; Hernández Garduño, Adolfo; Vázquez-Mellado, Janitzia

2010-08-01

Observation of monosodium urate (MSU) crystal is the gold standard for diagnosis of gout, but is rarely performed in daily clinical practice, and diagnosis is based on clinical judgment. Our aim was to identify clinical and paraclinical data included in the European League Against Rheumatism recommendations (EULARr) and American College of Rheumatology proposed criteria (ACRp) for diagnosis of gout in patients with chronic gout according to their attending rheumatologists. This cross-sectional and multicenter study included consecutive patients from outpatient clinics with a diagnosis of gout by their attending rheumatologists according to their expertise. The frequency of each item from the ACRp and EULARr was determined. Possible combinations of the items that were frequent, clinically relevant, and simple to evaluate in daily practice were determined. We studied 549 patients (96% men), mean age 50 +/- 14 years. Analysis of MSU crystals was performed in 15%. We selected 7 clinical criteria and 1 laboratory measure because of their frequency, importance, and simplicity to obtain: current or past history of: > 1 attack of acute arthritis (93%); mono or oligoarthritis attacks (74%); rapid progression of pain and swelling (< 24 hours; 74%); podagra (70%); erythema (56%); unilateral tarsitis (33%); tophi (52%); and hyperuricemia (93%). The chronic gout diagnosis (CGD) proposal comprised >or= 4/8 of these; 88% of patients had the criteria of the CGD proposal while 75% had 6/11 ACRp criteria (p = 0.001). When analysis of MSU crystals was added, 90.1% (CGD) and 83.9% (ACRp) met the criteria (p = 0.004). Current or past history of >or= 4/8 CGD parameters is highly suggestive of chronic gout.

Limitations of the Current Standards of Care for Treating Gout and Crystal Deposition in the Primary Care Setting: A Review.

PubMed

Keenan, Robert T

2017-02-01

This article outlines several important issues regarding the management of patients with gout. The topics discussed include best practices for gout based on the most current guidelines, opportunities for improving gout management, and current and emerging therapies for gout. [PubMed and Google Scholar databases] were search for all articles and trials published before 2016, using the key terms [hyperuricemia, gout, tophi, joint erosion, joint damage, treatment guidelines, American College of Rheumatology (ACR), European League Against Rheumatism (EULAR), flare, comorbidity, epidemiology, adherence, serum uric acid (sUA), monosodium urate (MSU), <6 mg/dL, MSU crystal formation, as well as individual drug names and classes of treatments of interest (allopurinol, febuxostat, colchicine, non-steroidal anti-inflammatories (NSAIDs)]. Studies were selected that presented data on gout treatment, including drugs under development, and on the management of gout from both the physician and patient perspectives. The reference lists of identified articles were searched manually for additional publications. Gout, a progressive debilitating form of inflammatory arthritis, is caused by factors that elevate serum uric acid (sUA) levels, leading to hyperuricemia. Continued elevated sUA can result in monosodium urate crystal deposition in joints and soft tissues, causing acute and chronic inflammation. Crystal deposition can lead to chronic gout, with an increased number of flares, tophi development, and structural joint damage. The aims of gout treatment are to reduce the sUA level to <6 mg/dL, to inhibit the formation of new crystals, and to promote the dissolution of existing crystals. Gout is often poorly managed for several reasons, including a lack of adherence to treatment guidelines by health care providers, patients' poor adherence to therapy, and differences between a provider's and patient's perspectives regarding treatment. Patients need to be educated about their diagnosis and management of the disease, such as the importance of compliance with long-term treatment. Gout treatment may also confounded by contraindications to current standards of therapy and the limitations of current treatment paradigms. Recently approved medications, as well as drugs under development, may provide new ways for reaching the sUA target and also "curing" the disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Cyclic GMP-dependent protein kinase II is necessary for macrophage M1 polarization and phagocytosis via toll-like receptor 2.

PubMed

Liao, Wei-Ting; You, Huey-Ling; Li, Changgui; Chang, Jan-Gowth; Chang, Shun-Jen; Chen, Chung-Jen

2015-05-01

Cyclic GMP-dependent protein kinase II (cGKII; PRKG2) phosphorylates a variety of biological targets and has been identified as a gout-susceptible gene. However, the regulatory role of cGKII in triggering gout disease has yet to be clarified. Thus, we plan to explore the specific function of cGKII in macrophages related to gout disease. By using cGKII gene knockdown method, we detected macrophage M1/M2 polarization, phagocytosis, and their responses to stimulation by monosodium urate (MSU). cGKII was highly expressed in M1 phenotype, but not in M2, and cGKII knockdown significantly inhibited macrophage M1 polarization by decreasing M1 chemokine markers (CXCL10 and CCL2) and downregulating phagocytosis function. We further identified that cGKII-associated phagocytosis was mediated by upregulating toll-like receptor 2 (TLR2) expression, but not by TLR4. Mimicking gout condition by MSU treatments, we found that MSU alone induced cGKII and TLR2 expression with increased M1 polarization markers and phagocytosis activity. It means that cGKII knockdown significantly inhibited this MSU-induced cGKII-TLR2-phagocytosis axis. Our study showed that cGKII plays a key role in M1 polarization, especially in TLR2-mediated phagocytosis under MSU exposure. The findings provide evidence for the possible role of cGKII as an inflammation exciter in gout disease. Gout-susceptible gene cGKII is necessary for macrophage M1 polarization. cGKII regulates M1 phagocytosis function via TLR2. Monosodium urate treatments increase cGKII expression and related function. This study reveals the role of cGKII in enhancing gouty inflammatory responses.

Endogenous and Uric Acid-Induced Activation of NLRP3 Inflammasome in Pregnant Women with Preeclampsia.

PubMed

Matias, Mariana Leticia; Romão, Mariana; Weel, Ingrid Cristina; Ribeiro, Vanessa Rocha; Nunes, Priscila Rezeck; Borges, Vera Therezinha; Araújo, João Pessoa; Peraçoli, José Carlos; de Oliveira, Leandro; Peraçoli, Maria Terezinha

2015-01-01

Preeclampsia (PE) is a specific syndrome of pregnancy, characterized by hypertension and proteinuria. This pathology is associated with hyperuricemia and elevated serum levels of inflammatory cytokines. Uric acid crystals may activate an intracellular complex called inflammasome, which is important for processing and release of inflammatory cytokines. This study investigated the state of monocyte activation, both endogenous and stimulated with monosodium urate (MSU), by gene expression of NLRP1 and NLRP3 receptors as well as their association with inflammatory cytokines expression. Monocytes were obtained from peripheral blood of 23 preeclamptic pregnant women, 23 normotensive pregnant women (NT) and 23 healthy non-pregnant women (NP). Inflammasome activation was evaluated by the gene expression of NLRP1, NLRP3, caspase-1, IL-1β, IL-18 and TNF-α by RT-qPCR in unstimulated monocytes (endogenous expression), or after cell stimulation with MSU (stimulated expression). The concentration of cytokines was assessed by ELISA. In preeclamptic pregnant women, gene expression of NLRP1, NLRP3, caspase-1, IL-1β and TNF-α by monocytes stimulated or not with MSU was significantly higher than in NT and NP groups. Stimulation of monocytes from preeclamptic and non-pregnant women with MSU induced increased gene expression of NLRP3, caspase-1 and TNF-α in relation to the endogenous expression in these groups, while this was not observed in the NT group. The cytokine determination showed that monocytes from women with PE produced higher endogenous levels of IL-1β, IL-18 and TNF-α compared to the other groups, while the stimulus with MSU led to higher production of these cytokines in preeclamptic group than in the NT group. In conclusion, the results showed increased basal gene expression of NLRP1 and NLRP3 receptors in monocytes from PE group. These cells stimulation with MSU demonstrates that uric acid plays a role in NLRP3 inflammasome activation, suggesting the participation of this inflammatory complex in the pathogenesis of preeclampsia.

Anti-Gouty Arthritis and Antihyperuricemia Effects of Sunflower (Helianthus annuus) Head Extract in Gouty and Hyperuricemia Animal Models.

PubMed

Li, Lanzhou; Teng, Meiyu; Liu, Yange; Qu, Yidi; Zhang, Yuanzhu; Lin, Feng; Wang, Di

2017-01-01

This study was performed to investigate the therapeutic effects and possible mechanisms of sunflower (Helianthus annuus) head extract (SHE) on gout. First, the components of sunflower head powder and SHE were analyzed systematically. SHE, especially SHEB (extracted with 20% ethanol and 80% double-distilled water), strongly suppressed the swelling of the ankles in rats with acute gout induced by monosodium urate (MSU) crystals and reduced the levels of uric acid and xanthine oxidase (XO) in mice with hyperuricemia induced by oteracil potassium and yeast extract powder. Hematoxylin and eosin staining indicated that SHEB reduced inflammation cells and increased the joint space in the ankle compared with the control rats with MSU-induced gout. In the rats with acute gout, among 13 detected inflammatory cytokines, SHEB significantly enhanced the serum levels of interleukin-10 and the monocyte chemoattractant protein 1 α . In the mice with hyperuricemia, SHEB reduced the levels of glutathione peroxidase, superoxide dismutase, malondialdehyde, and nitrogen monoxide in liver tissues. The potential therapeutic effects of SHE on gout are probably due to the production of anti-inflammatory cytokines and the suppression of XO activity via the modulation of oxidative stress status.

Anti-Gouty Arthritis and Antihyperuricemia Effects of Sunflower (Helianthus annuus) Head Extract in Gouty and Hyperuricemia Animal Models

PubMed Central

Li, Lanzhou; Teng, Meiyu; Liu, Yange; Qu, Yidi; Zhang, Yuanzhu

2017-01-01

This study was performed to investigate the therapeutic effects and possible mechanisms of sunflower (Helianthus annuus) head extract (SHE) on gout. First, the components of sunflower head powder and SHE were analyzed systematically. SHE, especially SHEB (extracted with 20% ethanol and 80% double-distilled water), strongly suppressed the swelling of the ankles in rats with acute gout induced by monosodium urate (MSU) crystals and reduced the levels of uric acid and xanthine oxidase (XO) in mice with hyperuricemia induced by oteracil potassium and yeast extract powder. Hematoxylin and eosin staining indicated that SHEB reduced inflammation cells and increased the joint space in the ankle compared with the control rats with MSU-induced gout. In the rats with acute gout, among 13 detected inflammatory cytokines, SHEB significantly enhanced the serum levels of interleukin-10 and the monocyte chemoattractant protein 1α. In the mice with hyperuricemia, SHEB reduced the levels of glutathione peroxidase, superoxide dismutase, malondialdehyde, and nitrogen monoxide in liver tissues. The potential therapeutic effects of SHE on gout are probably due to the production of anti-inflammatory cytokines and the suppression of XO activity via the modulation of oxidative stress status. PMID:28929115

TNF-α potentiates uric acid-induced interleukin-1β (IL-1β) secretion in human neutrophils.

PubMed

Yokose, Kohei; Sato, Shuzo; Asano, Tomoyuki; Yashiro, Makiko; Kobayashi, Hiroko; Watanabe, Hiroshi; Suzuki, Eiji; Sato, Chikako; Kozuru, Hideko; Yatsuhashi, Hiroshi; Migita, Kiyoshi

2018-05-01

Monosodium urate (MSU) has been shown to promote interleukin-1β (IL-1β) secretion in human monocytes, but the priming signals for NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway remains elusive. In this study, we investigated the role of Tumor necrosis factor-alpha (TNF-α) on MSU-mediated IL-1β induction in human neutrophils. Human neutrophils were stimulated with MSU, in the presence or absence of TNF-α priming. The cellular supernatants were analyzed for IL-1β, IL-18, and caspase-1 by enzyme-linked immunosorbent assay (ELISA) methods. Pro-IL-1β mRNA expressions in human neutrophils were analyzed by real-time PCR method. TNF-α stimulation induced pro-IL-1β mRNA expression; however, MSU stimulation did not induce pro-IL-1β mRNA expression in human neutrophils. TNF-α alone or MSU stimulation did not result in efficient IL-1β secretion in human neutrophils, whereas in TNF-α-primed neutrophils, MSU stimulation resulted in a marked IL-1β and IL-18 secretion. TNF-α-primed neutrophils secreted cleaved caspase-1 (p20), in response to MSU stimulation. Our data demonstrate that priming of human neutrophils with TNF-α promotes uric acid-mediated IL-1β secretion in the absence of microbial stimulation. These findings provide insights into the neutrophils-mediated inflammatory processes in gouty arthritis.

Urate Oxidase Purification by Salting-in Crystallization: Towards an Alternative to Chromatography

PubMed Central

Giffard, Marion; Ferté, Natalie; Ragot, François; El Hajji, Mohamed; Castro, Bertrand; Bonneté, Françoise

2011-01-01

Background Rasburicase (Fasturtec® or Elitek®, Sanofi-Aventis), the recombinant form of urate oxidase from Aspergillus flavus, is a therapeutic enzyme used to prevent or decrease the high levels of uric acid in blood that can occur as a result of chemotherapy. It is produced by Sanofi-Aventis and currently purified via several standard steps of chromatography. This work explores the feasibility of replacing one or more chromatography steps in the downstream process by a crystallization step. It compares the efficacy of two crystallization techniques that have proven successful on pure urate oxidase, testing them on impure urate oxidase solutions. Methodology/Principal Findings Here we investigate the possibility of purifying urate oxidase directly by crystallization from the fermentation broth. Based on attractive interaction potentials which are known to drive urate oxidase crystallization, two crystallization routes are compared: a) by increased polymer concentration, which induces a depletion attraction and b) by decreased salt concentration, which induces attractive interactions via a salting-in effect. We observe that adding polymer, a very efficient way to crystallize pure urate oxidase through the depletion effect, is not an efficient way to grow crystals from impure solution. On the other hand, we show that dialysis, which decreases salt concentration through its strong salting-in effect, makes purification of urate oxidase from the fermentation broth possible. Conclusions The aim of this study is to compare purification efficacy of two crystallization methods. Our findings show that crystallization of urate oxidase from the fermentation broth provides purity comparable to what can be achieved with one chromatography step. This suggests that, in the case of urate oxidase, crystallization could be implemented not only for polishing or concentration during the last steps of purification, but also as an initial capture step, with minimal changes to the current process. PMID:21589929

Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation.

PubMed

Kwak, Su-Bin; Koppula, Sushruta; In, Eun-Jung; Sun, Xiao; Kim, Young-Kyu; Kim, Myong-Ki; Lee, Kwang-Ho; Kang, Tae-Bong

2018-01-01

Artemisia princeps var. orientalis (Asteraceae, A. princeps ) is a well-known traditional medicinal herb used for treating various inflammatory disorders in Korea, Japan, China, and other Asian countries. In the present study, we investigated the effects of A. princeps extract (APO) on interleukin- (IL-) 1 β regulation and inflammasome activation in bone marrow-derived macrophages (BMDMs) and monosodium urate- (MSU-) induced peritonitis mouse model in vivo . The APO treatment to BMDMs primed with lipopolysaccharide (LPS) attenuated the NLRP3 and AIM2 inflammasome activation induced by danger signals, such as ATP, nigericin, silica crystals, and poly (dA:dT), respectively. Mechanistic study revealed that APO suppressed the ASC oligomerization and speck formation, which are required for inflammasome activation. APO treatment also reduced the ASC phosphorylation induced by the combination of LPS and a tyrosine phosphatase inhibitor. In vivo evaluation revealed that intraperitoneal administration of APO reduced IL-1 β levels, significantly ( p < 0.05) and dose dependently, in the MSU-induced peritonitis mouse model. In conclusion, our study is the first to report that the extract of A. princeps inhibits inflammasome activation through the modulation of ASC phosphorylation. Therefore, APO might be developed as therapeutic potential in the treatment of inflammasome-mediated inflammatory disorders, such as gouty arthritis.

Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation

PubMed Central

Kwak, Su-Bin; Koppula, Sushruta; In, Eun-Jung; Sun, Xiao; Kim, Young-Kyu

2018-01-01

Artemisia princeps var. orientalis (Asteraceae, A. princeps) is a well-known traditional medicinal herb used for treating various inflammatory disorders in Korea, Japan, China, and other Asian countries. In the present study, we investigated the effects of A. princeps extract (APO) on interleukin- (IL-) 1β regulation and inflammasome activation in bone marrow-derived macrophages (BMDMs) and monosodium urate- (MSU-) induced peritonitis mouse model in vivo. The APO treatment to BMDMs primed with lipopolysaccharide (LPS) attenuated the NLRP3 and AIM2 inflammasome activation induced by danger signals, such as ATP, nigericin, silica crystals, and poly (dA:dT), respectively. Mechanistic study revealed that APO suppressed the ASC oligomerization and speck formation, which are required for inflammasome activation. APO treatment also reduced the ASC phosphorylation induced by the combination of LPS and a tyrosine phosphatase inhibitor. In vivo evaluation revealed that intraperitoneal administration of APO reduced IL-1β levels, significantly (p < 0.05) and dose dependently, in the MSU-induced peritonitis mouse model. In conclusion, our study is the first to report that the extract of A. princeps inhibits inflammasome activation through the modulation of ASC phosphorylation. Therefore, APO might be developed as therapeutic potential in the treatment of inflammasome-mediated inflammatory disorders, such as gouty arthritis. PMID:29686531

IL-8 -251T/A and IL-12B 1188A/C polymorphisms are associated with gout in a Chinese male population.

PubMed

Liu, S; Yin, C; Chu, N; Han, L; Li, C

2013-01-01

Gout is caused by monosodium urate (MSU) crystal-induced inflammation of the joints and periarticular tissues. MSU crystals activate NALP3 and mediate interleukin (IL)-1β generation from its inactive pro-form, resulting in cellular activation and an IL-8-mediated neutrophil influx into the joint. IL-8 and IL-12 are important chemokines related to the initiation and amplification of acute and chronic inflammatory processes. In this study, we investigated whether the IL-8 -251T/A and IL-12 1188A/C polymorphisms are associated with susceptibility to gout in a Chinese Han male population. Overall, 387 patients with gout and 576 controls were included in this study. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). An association analysis was carried out using the χ2 test. A genotype-phenotype analysis was also conducted. The T allele of IL-8 -251 was associated with risk of gout [p = 0.031 (odds ratio (OR) 1.229, 95% confidence interval (CI) 1.019-1.483]. There was a clear link between the IL-12 1188 AA and AC genotypic and A allelic frequencies between gout cases and controls (p < 0.001, df = 2 by genotype; p < 0.001, OR 1.404, 95% CI 1.165-1.691 by allele). Our results suggest that the IL-8 -251T/A and IL-12B 1188A/C polymorphisms may be relevant host susceptibility factors for the development of gout.

Clinical significance of delta neutrophil index in the differential diagnosis between septic arthritis and acute gout attack within 24 hours after hospitalization

PubMed Central

Pyo, Jung Yoon; Kim, Dae Sik; Jung, Seung Min; Song, Jason Jungsik; Park, Yong-Beom; Lee, Sang-Won

2017-01-01

Abstract The most important differential diagnoses of acute monoarticular arthritis are septic arthritis and acute gout attack. Identifying infection is crucial in preventing the devastating outcome of septic arthritis. The delta neutrophil index (DNI) is a value that corresponds to the fraction of circulating immature granulocytes. As DNI reflects the burden of infection, we evaluated this index as a differentiating marker between septic arthritis and acute gout attack. The medical records of 149 patients with septic arthritis and 194 patients with acute gout attack were reviewed. A specific cell analyzer, ADVIA 2120, was used to measure DNI. Clinical and laboratory markers associated with predicting septic arthritis were assessed by using logistic regression. Patients with septic arthritis showed higher levels of DNI than those with acute gout attack (3.3 vs 0.6%, P < .001). Similar results were observed in patients without monosodium urate (MSU) crystal confirmation or those with normouricemia (3.3 vs 0.5 and 3.1 vs 0.7%, respectively; P < .001 for both). A DNI level of 1.9% was determined as the cutoff value for predicting septic arthritis. In the multivariate analysis, DNI was the most powerful independent value for predicting septic arthritis (odds ratio 14.003). This study showed the possibility of using DNI as a differentiating marker between septic arthritis and acute gout attack at the crucial early phase. DNI showed its relevance regardless of confirmation of MSU crystal deposition or serum level of uric acid. PMID:28746185

6-Shogaol inhibits monosodium urate crystal-induced inflammation--an in vivo and in vitro study.

PubMed

Sabina, Evan Prince; Rasool, Mahaboobkhan; Mathew, Lazar; Ezilrani, Panneerselvam; Indu, Haridas

2010-01-01

Gout is a rheumatic disease that is manifestated by an intense inflammation secondary to monosodium urate crystal deposition in joints. In the present study, we assessed the effect of 6-shogaol (isolated active principle from ginger) on monosodium urate crystal-induced inflammation in mice; an experimental model for gouty arthritis and compared it with that of the non-steroidal anti-inflammatory drug, indomethacin. Paw volume and levels/activities of lysosomal enzymes, lipid peroxidation, anti-oxidant status and inflammatory mediator TNF-alpha were determined in control and monosodium urate crystal-induced mice. The levels of beta-glucuronidase and lactate dehydrogenase were also measured in monosodium urate crystal-incubated polymorphonuclear leucocytes (PMNL) in vitro. The levels of lysosomal enzymes, lipid peroxidation, and inflammatory mediator tumour necrosis factor-alpha and paw volume were increased significantly and the activities of anti-oxidant status were in turn decreased in monosodium urate crystal-induced mice, whereas these changes were reverted to near normal levels upon 6-shogaol administration. In vitro, 6-shogaol reduced the level of beta-glucuronidase and lactate dehydrogenase in monosodium urate crystal-incubated polymorphonuclear leucocytes in concentration dependent manner when compared to control cells. The present results clearly indicated that 6-shogaol exerted a strong anti-inflammatory effect and can be regarded as useful tool for the treatment of acute gouty arthritis. Copyright 2009 Elsevier Ltd. All rights reserved.

The genetic basis of hyperuricaemia and gout.

PubMed

Merriman, Tony R; Dalbeth, Nicola

2011-01-01

Gout results from elevated urate concentrations in the blood (hyperuricaemia). When super-saturation of urate is reached, monosodium urate crystals form within the joint. In some individuals, these crystals elicit a painful self-limiting inflammatory response that is characteristic of acute gouty arthritis. The most important cause of hyperuricaemia is reduced excretion of uric acid in the urine. Uric acid excretion is coordinated by a suite of urate transport molecules expressed in the renal collecting tubules, and is a key physiological checkpoint in gout. Other checkpoints in gout are hepatic production of urate, monosodium urate crystal formation, and initiation of the acute inflammatory response. Genome-wide association scans for genes regulating serum urate concentrations have identified two major regulators of hyperuricaemia- the renal urate transporters SLC2A9 and ABCG2. The risk variants at each gene approximately double the risk for gout in people of Caucasian ancestry, with SLC2A9 also resulting in higher risk for gout in people of Polynesian ancestry, a diverse population characterized by a high prevalence of gout. Ongoing genetic association studies are identifying and confirming other genes controlling serum urate concentrations; although genome-wide association studies in gout per se await recruitment of suitable case sample sets. Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

An in vivo and in vitro potential of Indian ayurvedic herbal formulation Triphala on experimental gouty arthritis in mice.

PubMed

Sabina, E P; Rasool, M

2008-01-01

In the present study, we have investigated the efficacy of Indian ayurvedic herbal formulation Triphala on monosodium urate crystal-induced inflammation in mice; an experimental model for gouty arthritis and compared it with that of the non-steroidal anti-inflammatory drug, Indomethacin. The anti-arthritic effect of Triphala was evaluated by measuring changes in the paw volume, lysosomal enzyme activities, lipid peroxidation, anti-oxidant status and inflammatory mediator TNF-alpha in control and monosodium urate crystal-induced mice. The levels of beta-glucuronidase and lactate dehydrogenase were also measured in monosodium urate crystal-incubated polymorphonuclear leucocytes (PMNL). Triphala treatment (1 gm/kg/b.w. orally) significantly inhibited the paw volume and the levels of lysosomal enzymes, lipid peroxidation and inflammatory mediator tumour necrosis factor-alpha; however the anti-oxidant status was found to be increased in plasma, liver and spleen of monosodium urate crystal-induced mice when compared to control mice. In addition, beta-glucuronidase and lactate dehydrogenase level were reduced in Triphala (100 microg/ml) treated monosodium urate crystal-incubated polymorphonuclear leucocytes. In conclusion, the results obtained clearly indicated that Triphala exerted a strong anti-inflammatory effect against gouty arthritis.

An update on the genetics of hyperuricaemia and gout.

PubMed

Major, Tanya J; Dalbeth, Nicola; Stahl, Eli A; Merriman, Tony R

2018-06-01

A central aspect of the pathogenesis of gout is elevated urate concentrations, which lead to the formation of monosodium urate crystals. The clinical features of gout result from an individual's immune response to these deposited crystals. Genome-wide association studies (GWAS) have confirmed the importance of urate excretion in the control of serum urate levels and the risk of gout and have identified the kidneys, the gut and the liver as sites of urate regulation. The genetic contribution to the progression from hyperuricaemia to gout remains relatively poorly understood, although genes encoding proteins that are involved in the NLRP3 (NOD-, LRR- and pyrin domain-containing 3) inflammasome pathway play a part. Genome-wide and targeted sequencing is beginning to identify uncommon population-specific variants that are associated with urate levels and gout. Mendelian randomization studies using urate-associated genetic variants as unconfounded surrogates for lifelong urate exposure have not supported claims that urate is causal for metabolic conditions that are comorbidities of hyperuricaemia and gout. Genetic studies have also identified genetic variants that predict responsiveness to therapies (for example, urate-lowering drugs) for treatment of hyperuricaemia. Future research should focus on large GWAS (that include asymptomatic hyperuricaemic individuals) and on increasing the use of whole-genome sequencing data to identify uncommon genetic variants with increased penetrance that might provide opportunities for clinical translation.

New insights into the epidemiology of gout.

PubMed

Doherty, Michael

2009-05-01

Gout is a true crystal deposition disease caused by formation of monosodium urate crystals in joints and other tissues. It is a common inflammatory arthritis that has increased in prevalence in recent decades. Gout normally results from the interaction of genetic, constitutional and environmental risk factors. It is more common in men and strongly age related. A major determinant is the degree of elevation of uric acid levels above the saturation point for urate crystal formation, principally caused by inefficient renal urate excretion. Local joint tissue factors may influence the topography and extent of crystal deposition. Recent studies have provided information on dietary risk factors for gout: higher intakes of red meat, fructose and beer are independently associated with increased risk, whereas higher intakes of coffee, low-fat dairy products and vitamin C are associated with lower risk. Several renal urate transporters have been identified including URAT1 and SLC2A9 (GLUT9) and polymorphisms in these genes are associated with an increased risk of hyperuricaemia and gout. Many drugs influence serum uric acid levels through an effect on renal urate transport. Comorbidities, including the metabolic syndrome and impaired renal function are common in gout patients. The usual initial presentation of gout is with rapidly developing acute inflammatory monoarthritis, typically affecting the first MTP joint. If left untreated it may progress with recurrent acute attacks and eventual development of chronic symptoms and joint damage. New knowledge of the modifiable risk factors for gout can be integrated into the management strategy to optimize long-term patient outcomes.

Suppression of NLRP3 inflammasome by oral treatment with sulforaphane alleviates acute gouty inflammation.

PubMed

Yang, Gabsik; Yeon, Sang Hyeon; Lee, Hye Eun; Kang, Han Chang; Cho, Yong Yeon; Lee, Hye Suk; Lee, Joo Young

2018-04-01

The aetiology of gout is closely linked to the deposition of monosodium uric acid (MSU) crystals and the consequent activation of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. In this study, we investigated whether oral administration of an NLRP3 inhibitor would be effective to attenuate the symptoms of gout. The effects of oral administration with sulforaphane (SFN) were examined in two mouse models of acute gout induced by injection of MSU crystals into footpads or air pouch. The production of caspase-1 (p10) and IL-1β was examined by immunoblotting and ELISA as hallmarks of NLRP3 inflammasome activation. Oral administration of SFN attenuated MSU crystal-induced swelling and neutrophil recruitment in a mouse foot acute gout model, correlating with the suppression of the NLRP3 inflammasome activation in foot tissues. Consistently, oral administration of SFN blocked MSU-crystal-induced activation of the NLRP3 inflammasome in a mouse air pouch gout model. SFN suppressed NLRP3 inflammasome activation induced by MSU crystals, adenosine triphosphate and nigericin but not by poly(dA:dT) in primary mouse macrophages, independent of the reactive oxygen species pathway. SFN inhibited ligand-independent activation of the NLRP3 inflammasome, suggesting that SFN may act directly on the NLRP3 inflammasome complex. Oral administration of SFN effectively alleviated acute gouty inflammation by suppression of the NLRP3 inflammasome. Our results provide a novel strategy in which oral treatment with SFN may be beneficial in preventing acute attacks of gout.

Evaluation of liposome-encapsulated butorphanol tartrate for alleviation of experimentally induced arthritic pain in green-cheeked conures (Pyrrhura molinae)

PubMed Central

Paul-Murphy, Joanne R.; Krugner-Higby, Lisa A.; Tourdot, Renee L.; Sladky, Kurt K.; Klauer, Julia M.; Keuler, Nicholas S.; Brown, Carolyn S.; Heath, Timothy D.

2014-01-01

Objective To evaluate injection of microcrystalline sodium urate (MSU) for inducing articular pain in green-cheeked conures (Pyrrhura molinae) and the analgesic efficacy of liposome-encapsulated butorphanol tartrate (LEBT) by use of weight load data, behavioral scores, and fecal corticosterone concentration. Animals 8 conures. Procedures In a crossover study, conures were randomly assigned to receive LEBT (15 mg/kg) or liposomal vehicle subsequent to experimental induction of arthritis or sham injection. The MSU was injected into 1 tibiotarsal-tarsometatarsal (intertarsal) joint to induce arthritis (time 0). Weight-bearing load and behavioral scores were determined at 0, 2, 6, 26, and 30 hours. Results MSU injection into 1 intertarsal joint caused a temporary decrease in weight bearing on the affected limb. Treatment of arthritic conures with LEBT resulted in significantly more weight bearing on the arthritic limb than treatment with vehicle. Administration of vehicle to arthritic conures caused a decrease in activity and feeding behaviors during the induction phase of arthritis, but as the arthritis resolved, there was a significant increase in voluntary activity at 30 hours and feeding behaviors at 26 and 30 hours, compared with results for LEBT treatment of arthritic birds. Treatment with LEBT or vehicle in conures without arthritis resulted in similar measurements for weight bearing and voluntary and motivated behaviors. Conclusions and Clinical Relevance Experimental induction of arthritis in conures was a good method for evaluating tonic pain. Weight-bearing load was the most sensitive measure of pain associated with induced arthritis. Pain associated with MSU-induced arthritis was alleviated by administration of LEBT. PMID:19795935

Analgesic effects of carprofen and liposome-encapsulated butorphanol tartrate in Hispaniolan parrots (Amazona ventralis) with experimentally induced arthritis.

PubMed

Paul-Murphy, Joanne R; Sladky, Kurt K; Krugner-Higby, Lisa A; Stading, Ben R; Klauer, Julia M; Keuler, Nicholas S; Brown, Carolyn S; Heath, Timothy D

2009-10-01

To evaluate the microcrystalline sodium urate (MSU) method for inducing arthritis in parrots and to compare the analgesic efficacy of long-acting liposome-encapsulated butorphanol (LEBT), carprofen, or a combination of both. 20 Hispaniolan parrots. MSU was injected into a tibiotarsal-tarsometatarsal (intertarsal) joint to induce arthritis (time 0). Four treatments were compared (LEBT [15 mg/kg, SC] administered once at time 0; injections of carprofen [3 mg/kg, IM, q 12 h] starting at time 0; administration of LEBT plus carprofen; and a control treatment of saline [0.9% NaCl] solution). Weight load testing and behavioral scoring were conducted at 0, 2, 6, 26, and 30 hours. Injection of MSU into the intertarsal joint induced arthritis, which resolved within 30 hours. Treatment with LEBT or LEBT plus carprofen resulted in significantly greater weight-bearing load on the limb with induced arthritis, compared with the control treatment. Treatment with carprofen alone caused a slight but nonsignificant improvement in weight-bearing load on the arthritic limb, compared with the control treatment. Behaviors associated with motor activity and weight bearing differed between the control and analgesic treatments. Butorphanol was an effective treatment for pain associated with arthritis, but carprofen administered every 12 hours was insufficient. Injection of MSU to induce arthritis in a single joint was a good method for evaluating tonic pain in parrots, and measurement of the weight-bearing load was accurate for assessment of arthritic pain; however, behavioral changes associated with pain were subtle.

Erosive Pustular Dermatosis of the Scalp with Urate-Like Crystals.

PubMed

Emanuel, Patrick O; Paul, Sharad P

2017-01-01

Follicular urate-like crystals were first described in Necrotizing Infundibular Crystalline Folliculitis (NICF), a rare cutaneous disorder with multiple waxy folliculocentric papules. Similar crystal accumulation may be seen within follicular infundibulae as an incidental finding. We describe a case showing identical crystals occurring within the horn-like crusts of a patient with erosive pustular dermatosis of the scalp (EPDS), a condition which due to its presentation can often be mistaken for nonmelanoma skin cancer. A brief overview of erosive pustular dermatosis of the scalp (EPDS) is presented in this paper.

Dual-energy CT for the diagnosis of gout: an accuracy and diagnostic yield study.

PubMed

Bongartz, Tim; Glazebrook, Katrina N; Kavros, Steven J; Murthy, Naveen S; Merry, Stephen P; Franz, Walter B; Michet, Clement J; Veetil, Barath M Akkara; Davis, John M; Mason, Thomas G; Warrington, Kenneth J; Ytterberg, Steven R; Matteson, Eric L; Crowson, Cynthia S; Leng, Shuai; McCollough, Cynthia H

2015-06-01

To assess the accuracy of dual-energy CT (DECT) for diagnosing gout, and to explore whether it can have any impact on clinical decision making beyond the established diagnostic approach using polarising microscopy of synovial fluid (diagnostic yield). Diagnostic single-centre study of 40 patients with active gout, and 41 individuals with other types of joint disease. Sensitivity and specificity of DECT for diagnosing gout was calculated against a combined reference standard (polarising and electron microscopy of synovial fluid). To explore the diagnostic yield of DECT scanning, a third cohort was assembled consisting of patients with inflammatory arthritis and risk factors for gout who had negative synovial fluid polarising microscopy results. Among these patients, the proportion of subjects with DECT findings indicating a diagnosis of gout was assessed. The sensitivity and specificity of DECT for diagnosing gout was 0.90 (95% CI 0.76 to 0.97) and 0.83 (95% CI 0.68 to 0.93), respectively. All false negative patients were observed among patients with acute, recent-onset gout. All false positive patients had advanced knee osteoarthritis. DECT in the diagnostic yield cohort revealed evidence of uric acid deposition in 14 out of 30 patients (46.7%). DECT provides good diagnostic accuracy for detection of monosodium urate (MSU) deposits in patients with gout. However, sensitivity is lower in patients with recent-onset disease. DECT has a significant impact on clinical decision making when gout is suspected, but polarising microscopy of synovial fluid fails to demonstrate the presence of MSU crystals. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Urate-Lowering Agents in Asymptomatic Hyperuricemia: Role of Urine Sediment Analysis and Musculoskeletal Ultrasound.

PubMed

Viggiano, Davide; Gigliotti, Giuseppe; Vallone, Gianfranco; Giammarino, Anna; Nigro, Michelangelo; Capasso, Giovambattista

2018-01-01

Current urate-lowering therapy (ULT) includes three direct acting drugs (allopurinol, febuxostat, Rasburicase) and at least four 'indirect' drugs with other important targets (canagliflozin, losartan, fenofibrate and sevelamer). Moreover, the alcalinization of urines using bicarbonate can be used to dissolve urate crystals and the clinician may discontinue several drugs are known to increase serum levels of uric acid, such as diuretics, aspirin, cyclosporine, theophylline, mycophenolate and ACE inhibitors. While there is a consensus to start ULT in cases of symptomatic hyperuricemia (gout, urate-nephrolithiasis), the very frequent conditions of asymptomatic hyperuricemia remains a major conundrum. The effect of asymptomatic hyperuricemia on kidney function has had fluctuating positions over decades. The conflicting results might indicate: (i) the presence of counterbalancing positive and negative effects on kidney function of both serum uric acid and urate-lowering agents, (ii) the presence of a subpopulation of patients, as yet unidentified, which could truly benefit from a urate-lowering therapy. Therefore, today the treatment of asymptomatic hyperuricemia is not recommended nor excluded by current guidelines. Here we suggest that a possible guide for the treatment of asymptomatic hyperuricemia might be the presence of urate crystals in the urine sediment and/or signs of asymptomatic articular damage by urates, identified by musculo-skeletal ultrasound. Moreover, a watchful analysis of the trend in creatinine/eGFR, proteinuria or urate levels might also guide the clinician. Initiation of ULT and follow-up in cases of asymptomatic hyperuricemia should consider urine sediment analysis, musculoskeletal ultrasound and trends in creatinine, proteinuria and serum urate levels. © 2018 The Author(s). Published by S. Karger AG, Basel.

Discordant American College of Physicians and international rheumatology guidelines for gout management: consensus statement of the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN).

PubMed

Dalbeth, Nicola; Bardin, Thomas; Doherty, Michael; Lioté, Frédéric; Richette, Pascal; Saag, Kenneth G; So, Alexander K; Stamp, Lisa K; Choi, Hyon K; Terkeltaub, Robert

2017-09-01

In November 2016, the American College of Physicians (ACP) published a clinical practice guideline on the management of acute and recurrent gout. This guideline differs substantially from the latest guidelines generated by the American College of Rheumatology (ACR), European League Against Rheumatism (EULAR) and 3e (Evidence, Expertise, Exchange) Initiative, despite reviewing largely the same body of evidence. The Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) convened an expert panel to review the methodology and conclusions of these four sets of guidelines and examine possible reasons for discordance between them. The G-CAN position, presented here, is that the fundamental pathophysiological knowledge underlying gout care, and evidence from clinical experience and clinical trials, supports a treat-to-target approach for gout aimed at lowering serum urate levels to below the saturation threshold at which monosodium urate crystals form. This practice, which is truly evidence-based and promotes the steady reduction in tissue urate crystal deposits, is promoted by the ACR, EULAR and 3e Initiative recommendations. By contrast, the ACP does not provide a clear recommendation for urate-lowering therapy (ULT) for patients with frequent, recurrent flares or those with tophi, nor does it recommend monitoring serum urate levels of patients prescribed ULT. Results from emerging clinical trials that have gout symptoms as the primary end point are expected to resolve this debate for all clinicians in the near term future.

Performance of the 2015 American College of Rheumatology/European League Against Rheumatism gout classification criteria in Thai patients.

PubMed

Louthrenoo, Worawit; Jatuworapruk, Kanon; Lhakum, Panomkorn; Pattamapaspong, Nuttaya

2017-05-01

To evaluate the sensitivity and specificity of the 2015 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) gout classification criteria in Thai patients presenting with acute arthritis in a real-life setting. Data were analyzed on consecutive patients presenting with arthritis of less than 2 weeks duration. Sensitivity and specificity were calculated by using the presence of monosodium urate (MSU) crystals in the synovial fluid or tissue aspirate as gold standard for gout diagnosis. Subgroup analysis was performed in patients with early disease (≤2 years), established disease (>2 years), and those without tophus. Additional analysis also was performed in non-tophaceous gout patients, and patients with acute calcium pyrophosphate dihydrate crystal arthritis were used as controls. One hundred and nine gout and 74 non-gout patients participated in this study. Full ACR/EULAR classification criteria had sensitivity and specificity of 90.2 and 90.0%, respectively; and 90.2 and 85.0%, respectively, when synovial fluid microscopy was excluded. Clinical-only criteria yielded sensitivity and specificity of 79.8 and 87.8%, respectively. The criteria performed well among patients with early and non-tophaceous disease, but had lower specificity in patients with established disease. The variation of serum uric acid level was a major limitation of the classification criteria. The ACR/EULAR classification criteria had high sensitivity and specificity in Thai patients presenting with acute arthritis, even when clinical criteria alone were used.

C-type lectin domain family 12, member A: A common denominator in Behçet's syndrome and acute gouty arthritis.

PubMed

Oğuz, Ali Kemal; Yılmaz, Seda; Akar, Nejat; Özdağ, Hilal; Gürler, Aysel; Ateş, Aşkın; Oygür, Çağdaş Şahap; Kılıçoğlu, Sibel Serin; Demirtaş, Selda

2015-08-01

C-type lectin domain family 12, member A (CLEC12A) is a C-type lectin-like pattern recognition receptor capable of recognizing monosodium urate crystals. Monosodium urate crystals, the causative agents of gout are also among the danger-associated molecular patterns reflecting cellular injury/cell death. In response to monosodium urate crystals, CLEC12A effectively inhibits granulocyte and monocyte/macrophage functions and hence acts as a negative regulator of inflammation. Behçet's syndrome and gout are autoinflammatory disorders sharing certain pathological (neutrophilic inflammation), clinical (exaggerated response to monosodium urate crystals) and therapeutic (colchicine) features. We propose the hypothesis that decreased expression of CLEC12A is a common denominator in the hyperinflammatory responses observed in Behçet's syndrome and gout. Major lines of evidence supporting this hypothesis are: (1) Downregulation/deficiency of CLEC12A is associated with hyperinflammatory responses. (2) CLEC12A polymorphisms with functional and clinical implications have been documented in other inflammatory diseases. (3) Colchicine, a fundamental therapeutic agent used both in Behçet's syndrome and gout is shown to oppose the downregulation of CLEC12A. (4) Behçet's syndrome and gout are characterized by a hyperinflammatory response to monosodium urate crystals and other than gout, Behçet's syndrome is the only inflammatory condition exhibiting this exaggerated response. (5) Genomewide linkage and association studies of Behçet's syndrome collectively point to 12p12-13, the chromosomal region harboring CLEC12A. (6) Patients with severe forms of Behçet's syndrome underexpress CLEC12A with respect to patients with mild forms of the disease. If supported by well-designed, rigorous experiments, the forementioned hypothesis pertinent to CLEC12A will carry important implications for therapy, designing experimental models, and uncovering immunopathogenic mechanisms in Behçet's syndrome and gout. Copyright © 2015 Elsevier Ltd. All rights reserved.

Gout in the spotlight.

PubMed

So, Alexander

2008-01-01

Understanding how uric acid crystals provoke inflammation is crucial to improving our management of acute gout. It is well known that urate crystals stimulate monocytes and macrophages to elaborate inflammatory cytokines, but the tissue response of the synovium is less well understood. Microarray analysis of mRNA expression by these lining cells may help to delineate the genes that are modulated. Employing a murine air-pouch model, a number of genes expressed by innate immune cells were found to be rapidly upregulated by monosodium urate crystals. These findings provide new research avenues to investigate the physiopathology of gouty inflammation, and may eventually lead to new therapeutic targets in acute gout.

A preliminary neutron diffraction study of rasburicase, a recombinant urate oxidase enzyme, complexed with 8-azaxanthin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Budayova-Spano, Monika, E-mail: spano@embl-grenoble.fr; Institut Laue-Langevin, 6 Rue Jules Horowitz, BP 156, 38042 Grenoble; Bonneté, Françoise

2006-03-01

Neutron diffraction data of hydrogenated recombinant urate oxidase enzyme (Rasburicase), complexed with a purine-type inhibitor 8-azaxanthin, was collected to 2.1 Å resolution from a crystal grown in D{sub 2}O by careful control and optimization of crystallization conditions via knowledge of the phase diagram. Deuterium atoms were clearly seen in the neutron-scattering density map. Crystallization and preliminary neutron diffraction measurements of rasburicase, a recombinant urate oxidase enzyme expressed by a genetically modified Saccharomyces cerevisiae strain, complexed with a purine-type inhibitor (8-azaxanthin) are reported. Neutron Laue diffraction data were collected to 2.1 Å resolution using the LADI instrument from a crystal (grownmore » in D{sub 2}O) with volume 1.8 mm{sup 3}. The aim of this neutron diffraction study is to determine the protonation states of the inhibitor and residues within the active site. This will lead to improved comprehension of the enzymatic mechanism of this important enzyme, which is used as a protein drug to reduce toxic uric acid accumulation during chemotherapy. This paper illustrates the high quality of the neutron diffraction data collected, which are suitable for high-resolution structural analysis. In comparison with other neutron protein crystallography studies to date in which a hydrogenated protein has been used, the volume of the crystal was relatively small and yet the data still extend to high resolution. Furthermore, urate oxidase has one of the largest primitive unit-cell volumes (space group I222, unit-cell parameters a = 80, b = 96, c = 106 Å) and molecular weights (135 kDa for the homotetramer) so far successfully studied with neutrons.« less

Management of Gout and Hyperuricemia in CKD.

PubMed

Vargas-Santos, Ana Beatriz; Neogi, Tuhina

2017-09-01

Hyperuricemia and gout, the clinical manifestation of monosodium urate crystal deposition, are common in patients with chronic kidney disease (CKD). Although the presence of CKD poses additional challenges in gout management, effective urate lowering is possible for most patients with CKD. Initial doses of urate-lowering therapy are lower than in the non-CKD population, whereas incremental dose escalation is guided by regular monitoring of serum urate levels to reach the target level of <6mg/dL (or <5mg/dL for patients with tophi). Management of gout flares with presently available agents can be more challenging due to potential nephrotoxicity and/or contraindications in the setting of other common comorbid conditions. At present, asymptomatic hyperuricemia is not an indication for urate-lowering therapy, though emerging data may support a potential renoprotective effect. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Hyperuricaemia and gout.

PubMed

Shipley, M

2011-09-01

Gout is increasing in prevalence throughout the world, particularly in developed countries. The causes are dietary--purine-rich foods, high saturated fats, fructose-containing drinks and alcohol. Gout is also drug-related and associated with increased obesity, hypertension, insulin resistance and metabolic syndrome. Although very readily treated, there is evidence that physicians fail to optimise the treatment and achieve low enough serum urate levels, while patients fail to comply with the treatment and dietary advice. Standard treatment of acute attacks is with non-steroidal anti-inflammatory drugs, colchicine or steroids. The standard urate-lowering agents are allopurinol and uricosuric agents. Newer urate lowering agents are now available for refractory gout. Increased understanding of the membrane transporters involved in urate excretion in the kidney and the genes that control them and of the way that sodium urate crystals cause inflammation via the innate immune system and the inflammasome offers hope for new therapeutic approaches.

Rational pharmacotherapy (RPT) in goutology: Define the serum uric acid target & treat-to-target patient cohort and review on urate lowering therapy (ULT) applying synthetic drugs.

PubMed

Jansen, Tim L

2015-07-01

A gout revolution is at hand as can be seen from the number of publications and our recent increase in a better understanding of gout regarding imaging, regarding pathogenetic involvement of crystals, cells and cytokines, as well as regarding new pharmacotherapeutic options. We should now focus on rational pharmacotherapy to significantly improve gout care. With modern combinations of xanthine oxidase inhibition PLUS uricosuric all serum urate concentrations can be targeted. The pharmacotherapeutic literature of synthetic urate lowering treatment is reviewed and a plea is given for rational pharmacotherapy combining different modes of action aiming at the rheumatologically predefined optimal serum urate concentrations instead of a more reluctant approach to just lower a serum urate to any lower level with a fixed dose allopurinol. Copyright © 2014. Published by Elsevier SAS.

Lesinurad for the treatment of hyperuricaemia in people with gout.

PubMed

Robinson, Philip C; Dalbeth, Nicola

2017-12-01

Gout is a common form of inflammatory arthritis caused by deposition of monosodium urate crystals. The central strategy for effective long-term management of gout is serum urate lowering. Current urate-lowering drugs include both xanthine oxidase inhibitors and uricosuric agents. Lesinurad is a URAT1 inhibitor that selectively inhibits urate rebsorption at the proximal renal tubule. Lesinurad 200mg daily in combination with a xanthine oxidase is approved for urate-lowering therapy in patients with gout. Areas covered: The published literature was searched using Pubmed and additional information was obtained from publically available regulatory documents. Pre-clinical data and clinical trials of lesinurad are described. Serum urate-lowering efficacy and effects on other clinical endpoints are discussed. Adverse event data, focusing on renal safety are also presented. Expert opinion: Lesinurad is an effective urate-lowering drug that has a generally acceptable safety profile when used at 200mg daily dosing in combination with a xanthine oxidase inhibitor. The recent approval of fixed dose combination pills of lesinurad with allopurinol is an important step in improving adherence and reducing risk of renal adverse events. It remains to be seen if this therapy will provide additional benefit for gout management above improved use of widely available generic therapies.

Untangling the complex relationships between incident gout risk, serum urate, and its comorbidities.

PubMed

Sun, Mengying; Vazquez, Ana I; Reynolds, Richard J; Singh, Jasvinder A; Reeves, Mathew; Merriman, Tony R; Gaffo, Angelo L; Los Campos, Gustavo de

2018-05-03

Many gout comorbidities (e.g., hypertension) are correlated with serum urate. In this investigation, we identified risk factors (e.g., systolic blood pressure [SBP]), that (1) are associated with incident gout, (2) have effects on gout risk that cannot be fully explained by correlated differences in serum urate, and (3) may modulate the relationship between gout and serum urate. Using data from the Atherosclerosis Risk in Communities (ARIC) study, we estimated the unadjusted associations between gout and risk factors by calculating ORs and using chi-square tests. The adjusted associations were analyzed using logistic regression by sequentially adding (1) one risk factor at a time or (2) all risk factors, to a baseline model that includes serum urate only. Stepwise selection was used to select main effects. Two-way interactions of variables from the main effects model were also analyzed. Average gout incidence was 2.7 per 1000 people per year. Serum urate was highly associated with incident gout, with odd ratios of 3.16 [95% CI 2.11, 4.76] and 25.9 [95% CI 17.2, 38.4] for moderately high (6-8 mg/dl) and high serum urate (> 8 mg/dl), relative to normal serum urate (< 6 mg/dl), respectively. Ethnicity and SBP were independently and additively associated with gout after accounting for serum urate levels. No significant interactions were found between serum urate and ethnicity or SBP. Ethnicity and hypertension are predictive of gout risk, and the associations cannot be fully explained by serum urate. For serum urate levels near the crystallization threshold (6-8 mg/dl) African Americans and people with hypertension are at two to three times greater risk for developing gout. The gout risk for this group appears to increase before the onset of severe hyperuricemia.

Temporal evolution of urate crystal deposition over articular cartilage after successful urate-lowering therapy in patients with gout: An ultrasonographic perspective.

PubMed

Das, Shyamashis; Goswami, Rudra Prosad; Ghosh, Alakendu; Ghosh, Parasar; Lahiri, Debasish; Basu, Kaushik

2017-05-01

To detect evolution of ultrasonographic signs of deposition of monosodium urate crystals (MSUC) in gouty joints by serial ultrasonography after initiation of urate-lowering therapy (ULT). Adult gout patients were examined by serial ultrasonography after initiation of ULT with target serum uric acid (SUA) < 6 mg/dL. Thirty-eight male patients with gout with mean age of 50 ± 11 years, median disease duration of 48 months and baseline mean SUA level of 8.8 ± 1.5 mg/dL were recruited. Ultrasonographic evidence of MSUC deposition was detected in 89.74% of first metatarsophalangeal (MTP) joints and 27.63% of knee joints. Double contour sign (DCS), tophi, and hyperechoic spots (HES) were detected in 77.63%, 43.42%, and 19.74% of first MTPs, respectively. SUA level normalizes and plateaus after fourth month of follow-up. DCS thickness reduced significantly throughout the follow-up period. Overall, 86.25% DCS and 100% HES disappeared with median time of 6 months and 5.7 months, respectively. SUA normalization was the only significant predictor of DCS disappearance. Serial ultrasonographic determination of DCS, tophi, or HES during hypouricemic therapy is a noninvasive, effective method to detect the lowering of burden of urate load in gouty joints.

High catalytic activity and stability of Ni/CexZr1-xO2/MSU-H for CH4/CO2 reforming reaction

NASA Astrophysics Data System (ADS)

Chang, Xiaoqian; Liu, Bingsi; Xia, Hong; Amin, Roohul

2018-06-01

How to reduce emission of CO2 as greenhouse gases, which resulted in global warming, is of very important significance. A series of Ni/CexZr1-xO2/MSU-H catalysts was prepared by means of hexagonally ordered mesoporous MSU-H with thermal and hydrothermal stabilities, which is cheap and can be synthesized in the large scale. The 10%Ni/Ce0.75Zr0.25O2/MSU-H catalyst presents high catalytic activity, stability and the ability of coke-resistance for CH4/CO2 reforming reaction due to high SBET (428 m2/g) and smaller Nio nanoparticle size (3.14 nm). The high dispersed Nio nanoparticles over MSU-H promoted the decomposition of CH4 and the carbon species accumulated on active Nio sites reacting with crystal lattice oxygen in Ce0.75Zr0.25O2 to form CO molecules. In the meantime, the remained oxygen vacancies on the interface between Nio and Ce0.75Zr0.25O2 could be supplemented via CO2. HRTEM images and XRD results of Ni/Ce0.75Zr0.25O2/MSU-H verified that high dispersion of Ni nanoparticles over Ni/Ce0.75Zr0.25O2/MSU-H correlated closely with the synergistic action between Ce0.75Zr0.25O2 and MSU-H as well as hexagonally ordered structure of MSU-H, which can provide effectively the oxygen storage capacity and inhibit the formation of coke.

Improvement in Diagnosis and Treat-to-Target Management of Hyperuricemia in Gout: Results from the GEMA-2 Transversal Study on Practice.

PubMed

Perez Ruiz, Fernando; Sanchez-Piedra, Carlos A; Sanchez-Costa, Jesus T; Andrés, Mariano; Diaz-Torne, Cesar; Jimenez-Palop, Mercedes; De Miguel, Eugenio; Moragues, Carmen; Sivera, Francisca

2018-06-01

The objective of the study was to evaluate changes regarding main European League Against Rheumatism (EULAR) recommendations on diagnosis and treatment of gout compared to a previous assessment. The GEMA-2 (Gout Evaluation and MAnagement) is a transversal assessment of practice for gout by rheumatologists. Main outcome variables were improvement of the previous GEMA assessment regarding the rate of crystal-proven diagnosis and that reaching therapeutic serum urate target below 6 mg/dl at last visit. Other management variables (prophylaxis, treatment of flares, lifestyle change advice) were also evaluated along with general characteristics. The sample was powered to include at least 483 patients for up to 50% change. Data on management of 506 patients were retrieved from 38 out of 41 rheumatology units that participated in the previous GEMA audit. Crystal-proved diagnosis rate increased from 26% to 32% (31% improvement) and was higher in gout-dedicated practices; ultrasonography contributed to diagnosis in less than 1% of cases. Therapeutic serum urate at last visit improved from 41% to 64% of all patients (66% of patients on urate-lowering medications), in any case over 50% improvement from the previous assessment. The use of any urate-lowering medication available was not prescribed as per label dosing in patients who failed to achieve target serum urate. Clinical inertia to increase doses of either allopurinol or febuxostat was still present in clinical practice. Over 50% improvement in targeting therapeutic serum urate has been observed, but clinical inertia is still present. Diagnosis is still mostly clinically based, ultrasonography not being commonly contributive. Menarini España.

Coevolution of URAT1 and Uricase during Primate Evolution: Implications for Serum Urate Homeostasis and Gout

PubMed Central

Tan, Philip K.; Farrar, Jennifer E.; Gaucher, Eric A.; Miner, Jeffrey N.

2016-01-01

Uric acid is the highly insoluble end-product of purine metabolism in humans. Serum levels exceeding the solubility threshold can trigger formation of urate crystals resulting in gouty arthritis. Uric acid is primarily excreted through the kidneys with 90% reabsorbed back into the bloodstream through the uric acid transporter URAT1. This reabsorption process is essential for the high serum uric acid levels found in humans. We discovered that URAT1 proteins from humans and baboons have higher affinity for uric acid compared with transporters from rats and mice. This difference in transport kinetics of URAT1 orthologs, along with inability of modern apes to oxidize uric acid due to loss of the uricase enzyme, prompted us to ask whether these events occurred concomitantly during primate evolution. Ancestral URAT1 sequences were computationally inferred and ancient transporters were resurrected and assayed, revealing that affinity for uric acid was increased during the evolution of primates. This molecular fine-tuning occurred between the origins of simians and their diversification into New- and Old-World monkey and ape lineages. Remarkably, it was driven in large-part by only a few amino acid replacements within the transporter. This alteration in primate URAT1 coincided with changes in uricase that greatly diminished the enzymatic activity and took place 27–77 Ma. These results suggest that the modifications to URAT1 transporters were potentially adaptive and that maintaining more constant, high levels of serum uric acid may have provided an advantage to our primate ancestors. PMID:27352852

The neutron structure of urate oxidase resolves a long-standing mechanistic conundrum and reveals unexpected changes in protonation.

PubMed

Oksanen, Esko; Blakeley, Matthew P; El-Hajji, Mohamed; Ryde, Ulf; Budayova-Spano, Monika

2014-01-01

Urate oxidase transforms uric acid to 5-hydroxyisourate without the help of cofactors, but the catalytic mechanism has remained enigmatic, as the protonation state of the substrate could not be reliably deduced. We have determined the neutron structure of urate oxidase, providing unique information on the proton positions. A neutron crystal structure inhibited by a chloride anion at 2.3 Å resolution shows that the substrate is in fact 8-hydroxyxanthine, the enol tautomer of urate. We have also determined the neutron structure of the complex with the inhibitor 8-azaxanthine at 1.9 Å resolution, showing the protonation states of the K10-T57-H256 catalytic triad. Together with X-ray data and quantum chemical calculations, these structures allow us to identify the site of the initial substrate protonation and elucidate why the enzyme is inhibited by a chloride anion.

Coevolution of URAT1 and Uricase during Primate Evolution: Implications for Serum Urate Homeostasis and Gout.

PubMed

Tan, Philip K; Farrar, Jennifer E; Gaucher, Eric A; Miner, Jeffrey N

2016-09-01

Uric acid is the highly insoluble end-product of purine metabolism in humans. Serum levels exceeding the solubility threshold can trigger formation of urate crystals resulting in gouty arthritis. Uric acid is primarily excreted through the kidneys with 90% reabsorbed back into the bloodstream through the uric acid transporter URAT1. This reabsorption process is essential for the high serum uric acid levels found in humans. We discovered that URAT1 proteins from humans and baboons have higher affinity for uric acid compared with transporters from rats and mice. This difference in transport kinetics of URAT1 orthologs, along with inability of modern apes to oxidize uric acid due to loss of the uricase enzyme, prompted us to ask whether these events occurred concomitantly during primate evolution. Ancestral URAT1 sequences were computationally inferred and ancient transporters were resurrected and assayed, revealing that affinity for uric acid was increased during the evolution of primates. This molecular fine-tuning occurred between the origins of simians and their diversification into New- and Old-World monkey and ape lineages. Remarkably, it was driven in large-part by only a few amino acid replacements within the transporter. This alteration in primate URAT1 coincided with changes in uricase that greatly diminished the enzymatic activity and took place 27-77 Ma. These results suggest that the modifications to URAT1 transporters were potentially adaptive and that maintaining more constant, high levels of serum uric acid may have provided an advantage to our primate ancestors. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Critical Roles of Two Hydrophobic Residues within Human Glucose Transporter 9 (hSLC2A9) in Substrate Selectivity and Urate Transport*

PubMed Central

Long, Wentong; Panwar, Pankaj; Witkowska, Kate; Wong, Kenneth; O'Neill, Debbie; Chen, Xing-Zhen; Lemieux, M. Joanne; Cheeseman, Chris I.

2015-01-01

High blood urate levels (hyperuricemia) have been found to be a significant risk factor for cardiovascular diseases and inflammatory arthritis, such as hypertension and gout. Human glucose transporter 9 (hSLC2A9) is an essential protein that mainly regulates urate/hexose homeostasis in human kidney and liver. hSLC2A9 is a high affinity-low capacity hexose transporter and a high capacity urate transporter. Our previous studies identified a single hydrophobic residue in trans-membrane domain 7 of class II glucose transporters as a determinant of fructose transport. A mutation of isoleucine 335 to valine (I355V) in hSLC2A9 can reduce fructose transport while not affecting glucose fluxes. This current study demonstrates that the I335V mutant transports urate similarly to the wild type hSLC2A9; however, Ile-335 is necessary for urate/fructose trans-acceleration exchange to occur. Furthermore, Trp-110 is a critical site for urate transport. Two structural models of the class II glucose transporters, hSLC2A9 and hSLC2A5, based on the crystal structure of hSLC2A1 (GLUT1), reveal that Ile-335 (or the homologous Ile-296 in hSLC2A5) is a key component for protein conformational changes when the protein translocates substrates. The hSLC2A9 model also predicted that Trp-110 is a crucial site that could directly interact with urate during transport. Together, these studies confirm that hSLC2A9 transports both urate and fructose, but it interacts with them in different ways. Therefore, this study advances our understanding of how hSLC2A9 mediates urate and fructose transport, providing further information for developing pharmacological agents to treat hyperuricemia and related diseases, such as gout, hypertension, and diabetes. PMID:25922070

Survey Definitions of Gout for Epidemiologic Studies: Comparison With Crystal Identification as the Gold Standard.

PubMed

Dalbeth, Nicola; Schumacher, H Ralph; Fransen, Jaap; Neogi, Tuhina; Jansen, Tim L; Brown, Melanie; Louthrenoo, Worawit; Vazquez-Mellado, Janitzia; Eliseev, Maxim; McCarthy, Geraldine; Stamp, Lisa K; Perez-Ruiz, Fernando; Sivera, Francisca; Ea, Hang-Korng; Gerritsen, Martijn; Scire, Carlo A; Cavagna, Lorenzo; Lin, Chingtsai; Chou, Yin-Yi; Tausche, Anne-Kathrin; da Rocha Castelar-Pinheiro, Geraldo; Janssen, Matthijs; Chen, Jiunn-Horng; Cimmino, Marco A; Uhlig, Till; Taylor, William J

2016-12-01

To identify the best-performing survey definition of gout from items commonly available in epidemiologic studies. Survey definitions of gout were identified from 34 epidemiologic studies contributing to the Global Urate Genetics Consortium (GUGC) genome-wide association study. Data from the Study for Updated Gout Classification Criteria (SUGAR) were randomly divided into development and test data sets. A data-driven case definition was formed using logistic regression in the development data set. This definition, along with definitions used in GUGC studies and the 2015 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) gout classification criteria were applied to the test data set, using monosodium urate crystal identification as the gold standard. For all tested GUGC definitions, the simple definition of "self-report of gout or urate-lowering therapy use" had the best test performance characteristics (sensitivity 82%, specificity 72%). The simple definition had similar performance to a SUGAR data-driven case definition with 5 weighted items: self-report, self-report of doctor diagnosis, colchicine use, urate-lowering therapy use, and hyperuricemia (sensitivity 87%, specificity 70%). Both of these definitions performed better than the 1977 American Rheumatism Association survey criteria (sensitivity 82%, specificity 67%). Of all tested definitions, the 2015 ACR/EULAR criteria had the best performance (sensitivity 92%, specificity 89%). A simple definition of "self-report of gout or urate-lowering therapy use" has the best test performance characteristics of existing definitions that use routinely available data. A more complex combination of features is more sensitive, but still lacks good specificity. If a more accurate case definition is required for a particular study, the 2015 ACR/EULAR gout classification criteria should be considered. © 2016, American College of Rheumatology.

Activated fibrinolytic enzymes in the synovial fluid during acute arthritis induced by urate crystal injection in dogs.

PubMed

Morimoto, N; Sumi, H; Tsushima, H; Etou, Y; Yoshida, E; Mihara, H

1991-10-01

To identify the relationship of the severity of inflammation and fibrinolytic activity in arthritis, the fibrinolytic activity of synovial fluid was studied in acute experimental arthritis induced by injecting monosodium urate crystals into dogs' knee joints. The maximum activity in the synovial fluid was observed 6 h after crystal injection. It was inferred that the fibrinolytic activity was mainly due to plasminogen activator based on fibrin plate assays, substrate specificity, inhibitor effects and zymography. On the other hand, the activity of lysosomal enzymes (beta-glucuronidase and cathepsin G) reached a peak in the synovia after 12 h. Histological examination of the synovial membrane after 12 h also showed greater inflammation than at 6 h. The peak in fibrinolytic activity preceded the peak of lysosomal enzymes and histological changes. These results suggest that an increase in fibrinolytic activity by plasminogen activator may contribute to the development of an acute inflammatory response.

Multiplicative interaction of functional inflammasome genetic variants in determining the risk of gout.

PubMed

McKinney, Cushla; Stamp, Lisa K; Dalbeth, Nicola; Topless, Ruth K; Day, Richard O; Kannangara, Diluk Rw; Williams, Kenneth M; Janssen, Matthijs; Jansen, Timothy L; Joosten, Leo A; Radstake, Timothy R; Riches, Philip L; Tausche, Anne-Kathrin; Lioté, Frederic; So, Alexander; Merriman, Tony R

2015-10-13

The acute gout flare results from a localised self-limiting innate immune response to monosodium urate (MSU) crystals deposited in joints in hyperuricaemic individuals. Activation of the caspase recruitment domain-containing protein 8 (CARD8) NOD-like receptor pyrin-containing 3 (NLRP3) inflammasome by MSU crystals and production of mature interleukin-1β (IL-1β) is central to acute gouty arthritis. However very little is known about genetic control of the innate immune response involved in acute gouty arthritis. Therefore our aim was to test functional single nucleotide polymorphism (SNP) variants in the toll-like receptor (TLR)-inflammasome-IL-1β axis for association with gout. 1,494 gout cases of European and 863 gout cases of New Zealand (NZ) Polynesian (Māori and Pacific Island) ancestry were included. Gout was diagnosed by the 1977 ARA gout classification criteria. There were 1,030 Polynesian controls and 10,942 European controls including from the publicly-available Atherosclerosis Risk in Communities (ARIC) and Framingham Heart (FHS) studies. The ten SNPs were either genotyped by Sequenom MassArray or by Affymetrix SNP array or imputed in the ARIC and FHS datasets. Allelic association was done by logistic regression adjusting by age and sex with European and Polynesian data combined by meta-analysis. Sample sets were pooled for multiplicative interaction analysis, which was also adjusted by sample set. Eleven SNPs were tested in the TLR2, CD14, IL1B, CARD8, NLRP3, MYD88, P2RX7, DAPK1 and TNXIP genes. Nominally significant (P < 0.05) associations with gout were detected at CARD8 rs2043211 (OR = 1.12, P = 0.007), IL1B rs1143623 (OR = 1.10, P = 0.020) and CD14 rs2569190 (OR = 1.08; P = 0.036). There was significant multiplicative interaction between CARD8 and IL1B (P = 0.005), with the IL1B risk genotype amplifying the risk effect of CARD8. There is evidence for association of gout with functional variants in CARD8, IL1B and CD14. The gout-associated allele of IL1B increases expression of IL-1β - the multiplicative interaction with CARD8 would be consistent with a synergy of greater inflammasome activity (resulting from reduced CARD8) combined with higher levels of pre-IL-1β expression leading to increased production of mature IL-1β in gout.

Patients with gout can be cured in primary care.

PubMed

Rees, Frances; Doherty, Michael

2014-12-01

Gout affects 2.5% of the total UK population and is four times more common in men than women. The peak prevalence and incidence in the UK is in those aged 80-84 years. Gout is associated with comorbidities such as nephrolithiasis, chronic renal impairment, metabolic syndrome, depression and heart disease. It is also associated with increased mortality. Untreated gout can result in disabling irreversible peripheral joint damage and chronic usage-related pain. However, gout is curable. The pathogenic agents that cause gout i.e.urate crystals can be eliminated through a combination of effective patient education and evidence-based, targeted urate-lowering therapy. Gout is caused by the precipitation of monosodium urate crystals in and around a joint. The crystals preferentially form in peripheral, cooler joints and especially in those with osteoarthritis. It is thought that some of these preformed crystals within articular cartilage spill over into the joint space and trigger an acute attack of inflammation. Uric acid is predominantly renally excreted and the common heritable component of gout results from relative inefficiency of urate excretion. Chronic kidney disease, metabolic syndrome and drugs that reduce renal function (e.g. thiazide diuretics, beta-blockers and ACE inhibitors) will all lead to reduced elimination. Patients with chronic gout can present with monoarthritis but more commonly present with asymmetrical polyarthritis or tophi. Joints affected by osteoarthritis are preferentially targeted, the most common sites of involvement are feet, knees, hands and elbows. Diagnosis can be confirmed in primary care by taking a good history and clinical examination. An acute peripheral monoarthritis which reaches its peak within 24 hours and causes 'the worst pain ever experienced' is characteristic of an acute attack. A patient may have co-existing risk factors for gout such as osteoarthritis, obesity, hypertension, renal impairment, diuretic and antihypertensive drug use or increased beer or spirit consumption. A raised serum uric acid can confirm the diagnosis, however, this can be normal in the acute phase. Radiographs are rarely helpful but joint ultrasound may demonstrate deposits in cartilage, the synovium and peri-articular sites.

Relevant aspects of imaging in the diagnosis and management of gout.

PubMed

De Avila Fernandes, Eloy; Bergamaschi, Samuel Brighenti; Rodrigues, Tatiane Cantarelli; Dias, Gustavo Coelho; Malmann, Ralff; Ramos, Germano Martins; Monteiro, Soraya Silveira

Gout is an inflammatory arthritis characterized by the deposition of monosodium urate crystals in the synovial membrane, articular cartilage and periarticular tissues leading to inflammation. Men are more commonly affected, mainly after the 5th decade of life. Its incidence has been growing with the population aging. In the majority of the cases, the diagnosis is made by clinical criteria and synovial fluid analysis, in search for monosodium urate crystals. Nonetheless, gout may sometimes have atypical presentations, complicating the diagnosis. In these situations, imaging methods have a fundamental role, aiding in the diagnostic confirmation or excluding other possible differential diagnosis. Conventional radiographs are still the most commonly used method in gout patients' evaluation; nevertheless, this is not a sensitive method, since it detect only late alterations. In the last years, there have been several advances in imaging methods for gout patients. Ultrasound has shown a great accuracy in the diagnosis of gout, identifying monosodium urate deposits in the synovial membrane and articular cartilage, in detecting and characterizing tophi and in identifying tophaceous tendinopathy and enthesopathy. Ultrasound has also been able to show crystal deposition in patients with articular pain in the absence of a classical gout crisis. Computed tomography is an excellent method for detecting bone erosions, being useful in spine involvement. Dual-energy CT is a new method able to provide information about the chemical composition of tissues, with high accuracy in the identification of monosodium urate deposits, even in the early stages of the disease and in cases of difficult characterization. Magnetic resonance imaging is useful in the evaluation of deep tissues not accessible by ultrasound. Besides the diagnosis, with the emergence of new drugs that aim to reduce tophaceous burden, imaging methods have become useful tools in monitoring the treatment of patients with gout. Copyright © 2016. Published by Elsevier Editora Ltda.

Imaging of gout: an overview.

PubMed

Dalbeth, Nicola; Doyle, Anthony J

2012-12-01

The diverse clinical states and sites of pathology in gout provide challenges when considering the features apparent on imaging. Ideally, an imaging modality should capture all aspects of disease including monosodium urate crystal deposition, acute inflammation, tophus, tissue remodelling and complications of disease. The modalities used in gout include conventional radiography, ultrasonography, magnetic resonance imaging, computed tomography and dual-energy computed tomography. This review discusses the role of each of these imaging modalities in gout, focussing on the imaging characteristics, role in gout diagnosis and role for disease monitoring. Ultrasonography and dual-energy computed tomography are particularly promising methods for both non-invasive diagnosis and monitoring of disease. The observation that ultrasonographic appearances of monosodium urate crystal deposition can be observed in patients with hyperuricaemia but no other clinical features of gout raises important questions about disease definitions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Common gene variants interactions related to uric acid transport are associated with knee osteoarthritis susceptibility.

PubMed

Fernández-Torres, Javier; Martínez-Nava, Gabriela Angélica; Oliviero, Francesca; López-Reyes, Alberto Gabriel; Martínez-Flores, Karina; Garrido-Rodríguez, Daniela; Francisco-Balderas, Adriana; Zamudio-Cuevas, Yessica

2018-06-01

Background The presence of genetic variants in the uric acid (UA) transporters can be associated with hyperuricemia, and therefore with an increased risk of monosodium urate (MSU) crystal precipitation. The inflammatory process triggered by these crystals lead to cartilage damage which, in turn, could promote knee osteoarthritis (KOA). Objective To determine whether genetic polymorphisms of the UA transporters and its interactions are associated with KOA. Materials and Methods Two hundred forty-three unrelated Mexican-mestizo individuals were recruited for this case control-study. Ninety-three of them were KOA patients but without gout, and one hundred and fifty healthy individuals with no symptoms or signs of KOA were recruited as controls. Forty-one single nucleotide polymorphisms (SNPs) involved in the UA transporters were genotyped with OpenArray technology in a QuantStudio 12K flex-System both cases and controls. Results After adjusting by age, gender, BMI and ancestry, significant associations were found for 8 SNPs: rs1260326 (GCKR), rs780093 (GCKR), rs17050272 (INHBB), rs1471633 (PDZK1), rs12129861 (PDZK1), rs7193778 (IGF1R), rs17786744 (STC1) and rs1106766 (R3HDM2). With respect to gene-gene interactions, the pairwise interactions of rs112129861 (PDZK1) and rs7193778 (IGF1R); rs17050272 (INHBB) and rs1106766 (R3HDM2); rs1106766 (R3HDM2) and rs780093 (GCKR); rs1260326 (GCKR) and rs17786744 (STC1); and rs17786744 (STC1) and rs1106766 (R3HDM2), make it possible to visualize the synergistic or antagonistic effect of their genotypes or alleles on KOA development. Conclusions Our preliminary results show that the common gene variants related with the UA transport are associated with KOA in the Mexican population. Further studies must be done to corroborate it.

Recent insights into the pathogenesis of hyperuricaemia and gout.

PubMed

Riches, Philip L; Wright, Alan F; Ralston, Stuart H

2009-10-15

Gout is a common rheumatic disease in humans which is characterized by elevation in serum uric acid levels, and deposition of uric acid crystals in the joint. Hyperuricaemia is the primary risk factor for the development of gout and primates have uniquely high levels of serum uric acid due to missense mutations in the uricase gene. Levels of serum uric acid are known to be highly heritable, and mutations in genes which encode enzymes in the purine salvage pathway have long been recognized as rare causes of gout. Until recently, however, little has been known about the genetic determinants of urate metabolism and susceptibility to gout in the general population. Over recent months, a series of large scale genome wide association studies have been performed which have shed new light on the genes which regulate serum uric acid levels and susceptibility to gout. Most of these genes seem to be involved in regulating the renal excretion of uric acid which underscores the importance of reduced urate excretion as opposed to increased endogenous production as a cause of gout. Further work will now be required to investigate the mechanisms by which these genetic variants regulate urate excretion and serum urate levels. However, it seems likely that the genes so far identified will represent new molecular targets for the design of drugs to enhance urate excretion and the genetic variants that predispose to gout might be of value as genetic markers of susceptibility to gout.

Xanthine oxidoreductase and its inhibitors: relevance for gout.

PubMed

Day, Richard O; Kamel, Bishoy; Kannangara, Diluk R W; Williams, Kenneth M; Graham, Garry G

2016-12-01

Xanthine oxidoreductase (XOR) is the rate-limiting enzyme in purine catabolism and converts hypoxanthine to xanthine, and xanthine into uric acid. When concentrations of uric acid exceed its biochemical saturation point, crystals of uric acid, in the form of monosodium urate, emerge and can predispose an individual to gout, the commonest form of inflammatory arthritis in men aged over 40 years. XOR inhibitors are primarily used in the treatment of gout, reducing the formation of uric acid and thereby, preventing the formation of monosodium urate crystals. Allopurinol is established as first-line therapy for gout; a newer alternative, febuxostat, is used in patients unable to tolerate allopurinol. This review provides an overview of gout, a detailed analysis of the structure and function of XOR, discussion on the pharmacokinetics and pharmacodynamics of XOR inhibitors-allopurinol and febuxostat, and the relevance of XOR in common comorbidities of gout. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Diagnosis, treatment, and prevention of gout.

PubMed

Hainer, Barry L; Matheson, Eric; Wilkes, R Travis

2014-12-15

Gout is characterized by painful joint inflammation, most commonly in the first metatarsophalangeal joint, resulting from precipitation of monosodium urate crystals in a joint space. Gout is typically diagnosed using clinical criteria from the American College of Rheumatology. Diagnosis may be confirmed by identification of monosodium urate crystals in synovial fluid of the affected joint. Acute gout may be treated with nonsteroidal anti-inflammatory drugs, corticosteroids, or colchicine. To reduce the likelihood of recurrent flares, patients should limit their consumption of certain purine-rich foods (e.g., organ meats, shellfish) and avoid alcoholic drinks (especially beer) and beverages sweetened with high-fructose corn syrup. Consumption of vegetables and low-fat or nonfat dairy products should be encouraged. The use of loop and thiazide diuretics can increase uric acid levels, whereas the use of the angiotensin receptor blocker losartan increases urinary excretion of uric acid. Reduction of uric acid levels is key to avoiding gout flares. Allopurinol and febuxostat are first-line medications for the prevention of recurrent gout, and colchicine and/or probenecid are reserved for patients who cannot tolerate first-line agents or in whom first-line agents are ineffective. Patients receiving urate-lowering medications should be treated concurrently with nonsteroidal anti-inflammatory drugs, colchicine, or low-dose corticosteroids to prevent flares. Treatment should continue for at least three months after uric acid levels fall below the target goal in those without tophi, and for six months in those with a history of tophi.

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.

PubMed

Soskind, Rose; Abazia, Daniel T; Bridgeman, Mary Barna

2017-08-01

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'. All published articles regarding therapeutic management of gout and hyperuricemia were evaluated. References of selected articles, data from poster presentations, and abstract publications were additionally reviewed. Expert opinion: Numerous therapies are currently available to managing acute gout flares and for lowering serum urate levels; advances in the understanding of the pathophysiology of this disorder has led to the emergence of targeted therapies and novel biologic preparations currently in development which may improve the clinical management of severe or refractory cases of disease that fail to respond to traditional therapies.

Physiology of Hyperuricemia and Urate-Lowering Treatments.

PubMed

Benn, Caroline L; Dua, Pinky; Gurrell, Rachel; Loudon, Peter; Pike, Andrew; Storer, R Ian; Vangjeli, Ciara

2018-01-01

Gout is the most common form of inflammatory arthritis and is a multifactorial disease typically characterized by hyperuricemia and monosodium urate crystal deposition predominantly in, but not limited to, the joints and the urinary tract. The prevalence of gout and hyperuricemia has increased in developed countries over the past two decades and research into the area has become progressively more active. We review the current field of knowledge with emphasis on active areas of hyperuricemia research including the underlying physiology, genetics and epidemiology, with a focus on studies which suggest association of hyperuricemia with common comorbidities including cardiovascular disease, renal insufficiency, metabolic syndrome and diabetes. Finally, we discuss current therapies and emerging drug discovery efforts aimed at delivering an optimized clinical treatment strategy.

Expression, Purification, and Structural Insights for the Human Uric Acid Transporter, GLUT9, Using the Xenopus laevis Oocytes System

PubMed Central

Clémençon, Benjamin; Lüscher, Benjamin P.; Fine, Michael; Baumann, Marc U.; Surbek, Daniel V.; Bonny, Olivier; Hediger, Matthias A.

2014-01-01

The urate transporter, GLUT9, is responsible for the basolateral transport of urate in the proximal tubule of human kidneys and in the placenta, playing a central role in uric acid homeostasis. GLUT9 shares the least homology with other members of the glucose transporter family, especially with the glucose transporting members GLUT1-4 and is the only member of the GLUT family to transport urate. The recently published high-resolution structure of XylE, a bacterial D-xylose transporting homologue, yields new insights into the structural foundation of this GLUT family of proteins. While this represents a huge milestone, it is unclear if human GLUT9 can benefit from this advancement through subsequent structural based targeting and mutagenesis. Little progress has been made toward understanding the mechanism of GLUT9 since its discovery in 2000. Before work can begin on resolving the mechanisms of urate transport we must determine methods to express, purify and analyze hGLUT9 using a model system adept in expressing human membrane proteins. Here, we describe the surface expression, purification and isolation of monomeric protein, and functional analysis of recombinant hGLUT9 using the Xenopus laevis oocyte system. In addition, we generated a new homology-based high-resolution model of hGLUT9 from the XylE crystal structure and utilized our purified protein to generate a low-resolution single particle reconstruction. Interestingly, we demonstrate that the functional protein extracted from the Xenopus system fits well with the homology-based model allowing us to generate the predicted urate-binding pocket and pave a path for subsequent mutagenesis and structure-function studies. PMID:25286413

β-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares.

PubMed

Goldberg, Emily L; Asher, Jennifer L; Molony, Ryan D; Shaw, Albert C; Zeiss, Caroline J; Wang, Chao; Morozova-Roche, Ludmilla A; Herzog, Raimund I; Iwasaki, Akiko; Dixit, Vishwa Deep

2017-02-28

Aging and lipotoxicity are two major risk factors for gout that are linked by the activation of the NLRP3 inflammasome. Neutrophil-mediated production of interleukin-1β (IL-1β) drives gouty flares that cause joint destruction, intense pain, and fever. However, metabolites that impact neutrophil inflammasome remain unknown. Here, we identified that ketogenic diet (KD) increases β-hydroxybutyrate (BHB) and alleviates urate crystal-induced gout without impairing immune defense against bacterial infection. BHB inhibited NLRP3 inflammasome in S100A9 fibril-primed and urate crystal-activated macrophages, which serve to recruit inflammatory neutrophils in joints. Consistent with reduced gouty flares in rats fed a ketogenic diet, BHB blocked IL-1β in neutrophils in a NLRP3-dependent manner in mice and humans irrespective of age. Mechanistically, BHB inhibited the NLRP3 inflammasome in neutrophils by reducing priming and assembly steps. Collectively, our studies show that BHB, a known alternate metabolic fuel, is also an anti-inflammatory molecule that may serve as a treatment for gout. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Conventional Radiology in Crystal Arthritis: Gout, Calcium Pyrophosphate Deposition, and Basic Calcium Phosphate Crystals.

PubMed

Jacques, Thibaut; Michelin, Paul; Badr, Sammy; Nasuto, Michelangelo; Lefebvre, Guillaume; Larkman, Neal; Cotten, Anne

2017-09-01

This article reviews the main radiographic features of crystal deposition diseases. Gout is linked to monosodium urate crystals. Classic radiographic features include subcutaneous tophi, large and well-circumscribed paraarticular bone erosions, and exuberant bone hyperostosis. Calcium pyrophosphate deposition (CPPD) can involve numerous structures, such as hyaline cartilages, fibrocartilages, or tendons. CPPD arthropathy involves joints usually spared by osteoarthritis. Basic calcium phosphate deposits are periarticular or intraarticular. Periarticular calcifications are amorphous, dense, and round or oval with well-limited borders, and most are asymptomatic. When resorbing, they become cloudy and less dense with an ill-defined shape and can migrate into adjacent structures. Copyright © 2017 Elsevier Inc. All rights reserved.

Crystal-proven Gout and Characteristic Gout Severity Factors are Associated with Cardiovascular Disease.

PubMed

Disveld, Iris J M; Fransen, Jaap; Rongen, Gerard A; Kienhorst, Laura B E; Zoakman, Sahel; Janssens, Hein J E M; Janssen, Matthijs

2018-04-15

Our aim was to examine the prevalence of cardiovascular disease (CVD) in patients with crystal-proven gout compared to arthritis controls. Further, we analyzed the association between characteristic gout severity factors and CVD to provide further support for a pathogenetic relationship between gout and CVD. Patients with arthritis referred for diagnosis were consecutively included in the Gout Arnhem-Liemers cohort. Joint fluid analysis was performed in all referred patients; controls were negative for crystals. Patients' characteristics and different manifestations of CVD and gout severity factors (disease duration, attack frequency, tophi, affected joints, high serum urate acid level, joint damage) were collected. Gout patients were compared with controls for the prevalence of CVD. In addition, the association between characteristic gout severity factors and presence of CVD was analyzed. Data from 700 gout patients and 276 controls were collected. CVD was present in 47% (95% CI 44%-51%) and 24% (95% CI 19%-29%) of gout patients and controls, respectively. Corrected for confounders, gout was still strongly associated with an increased prevalence of CVD compared to controls (OR 3.39, 95% CI 2.37-4.84). In patients with gout, disease duration ≥ 2 years, oligo- or polyarthritis, serum urate acid > 0.55 mmol/l at presentation, and joint damage were independently (p < 0.05) associated with prevalent CVD. Crystal-proven gout was strongly associated with an increased prevalence of CVD. In patients with gout, characteristic gout severity factors were associated with CVD.

Plasma Urate and Risk of a Hospital Stay with AKI: The Atherosclerosis Risk in Communities Study.

PubMed

Greenberg, Keiko I; McAdams-DeMarco, Mara A; Köttgen, Anna; Appel, Lawrence J; Coresh, Josef; Grams, Morgan E

2015-05-07

Higher urate levels are associated with higher risk of CKD, but the association between urate and AKI is less established. This study evaluated the risk of hospitalized AKI associated with urate concentrations in a large population-based cohort. To explore whether urate itself causes kidney injury, the study also evaluated the relationship between a genetic urate score and AKI. A total of 11,011 participants from the Atherosclerosis Risk in Communities study were followed from 1996-1998 (baseline) to 2010. The association between baseline plasma urate and risk of hospitalized AKI, adjusted for known AKI risk factors, was determined using Cox regression. Interactions of urate with gout and CKD were tested. Mendelian randomization was performed using a published genetic urate score among the participants with genetic data (n=7553). During 12 years of follow-up, 823 participants were hospitalized with AKI. Overall, mean participant age was 63.3 years, mean eGFR was 86.3 ml/min per 1.73 m(2), and mean plasma urate was 5.6 mg/dl. In patients with plasma urate >5.0 mg/dl, there was a 16% higher risk of hospitalized AKI for each 1-mg/dl higher urate (adjusted hazard ratio, 1.16; 95% confidence interval, 1.10 to 1.23; P<0.001). When stratified by history of gout, the association between higher urate and AKI was significant only in participants without a history of gout (P for interaction=0.02). There was no interaction of CKD and urate with AKI, nor was there an association between genetic urate score and AKI. Plasma urate >5.0 mg/dl was independently associated with risk of hospitalized AKI; however, Mendelian randomization did not provide evidence for a causal role of urate in AKI. Further research is needed to determine whether lowering plasma urate might reduce AKI risk. Copyright © 2015 by the American Society of Nephrology.

Registration of "MSU E5024" wheat

USDA-ARS?s Scientific Manuscript database

'MSU E5024' (Reg. No. CV-1077, PI 664078) soft white winter wheat (Triticum aestivum L.) was developed by Michigan State University (MSU) AgBioResearch and released in 2011 via exclusive licensing agreements through MSU Technologies. In addition to researchers at MSU, USDA-ARS researchers at the Sof...

Mangiferin Inhibits Renal Urate Reabsorption by Modulating Urate Transporters in Experimental Hyperuricemia.

PubMed

Yang, Hua; Gao, Lihui; Niu, Yanfen; Zhou, Yuanfang; Lin, Hua; Jiang, Jing; Kong, Xiangfu; Liu, Xu; Li, Ling

2015-01-01

Mangiferin, a natural glucosyl xanthone from the leaves of Mangifera indica L., was previously shown to exert potent hypouricemic effects associated with inhibition of the activity of xanthine dehydrogenase/oxidase. The present study aimed to evaluate its uricosuric effect and possible molecular mechanisms underlying the renal urate transporters responsible for urate reabsorption in vivo. Mangiferin (1.5-24.0 mg/kg) was administered intragastrically to hyperuricemic mice and rats induced by the intraperitoneal injection of uric acid and potassium oxonate, respectively. The uricosuric effect was evaluated by determining the serum and urinary urate levels as well as fractional excretion of uric acid (FEUA). The mRNA and protein levels of renal urate-anion transporter 1 (URAT1), organic anion transporter 10 (OAT10), glucose transporter 9 (GLUT9), and PDZ domain-containing protein (PDZK1) were analyzed. The administration of mangiferin significantly decreased the serum urate levels in hyperuricemic mice in a dose- and time-dependent manner. In hyperuricemic rats, mangiferin also reduced the serum urate levels and increased the urinary urate levels and FEUA. These results indicate that mangiferin has uricosuric effects. Further examination showed that mangiferin markedly inhibited the mRNA and protein expression of renal URAT1, OAT10, and GLUT9 in hyperuricemic rats, but did not interfere with PDZK1 expression. Taken together, these findings suggest that mangiferin promotes urate excretion by the kidney, which may be related to the inhibition of urate reabsorption via downregulation of renal urate transporters.

Urate as a Physiological Substrate for Myeloperoxidase

PubMed Central

Meotti, Flavia C.; Jameson, Guy N. L.; Turner, Rufus; Harwood, D. Tim; Stockwell, Samantha; Rees, Martin D.; Thomas, Shane R.; Kettle, Anthony J.

2011-01-01

Urate and myeloperoxidase (MPO) are associated with adverse outcomes in cardiovascular disease. In this study, we assessed whether urate is a likely physiological substrate for MPO and if the products of their interaction have the potential to exacerbate inflammation. Urate was readily oxidized by MPO and hydrogen peroxide to 5-hydroxyisourate, which decayed to predominantly allantoin. The redox intermediates of MPO were reduced by urate with rate constants of 4.6 × 105 m−1 s−1 for compound I and 1.7 × 104 m−1 s−1 for compound II. Urate competed with chloride for oxidation by MPO and at hyperuricemic levels is expected to be a substantive substrate for the enzyme. Oxidation of urate promoted super-stoichiometric consumption of glutathione, which indicates that it is converted to a free radical intermediate. In combination with superoxide and hydrogen peroxide, MPO oxidized urate to a reactive hydroperoxide. This would form by addition of superoxide to the urate radical. Urate also enhanced MPO-dependent consumption of nitric oxide. In human plasma, stimulated neutrophils produced allantoin in a reaction dependent on the NADPH oxidase, MPO and superoxide. We propose that urate is a physiological substrate for MPO that is oxidized to the urate radical. The reactions of this radical with superoxide and nitric oxide provide a plausible link between urate and MPO in cardiovascular disease. PMID:21266577

Human Sodium Phosphate Transporter 4 (hNPT4/SLC17A3) as a Common Renal Secretory Pathway for Drugs and Urate*

PubMed Central

Jutabha, Promsuk; Anzai, Naohiko; Kitamura, Kenichiro; Taniguchi, Atsuo; Kaneko, Shuji; Yan, Kunimasa; Yamada, Hideomi; Shimada, Hidetaka; Kimura, Toru; Katada, Tomohisa; Fukutomi, Toshiyuki; Tomita, Kimio; Urano, Wako; Yamanaka, Hisashi; Seki, George; Fujita, Toshiro; Moriyama, Yoshinori; Yamada, Akira; Uchida, Shunya; Wempe, Michael F.; Endou, Hitoshi; Sakurai, Hiroyuki

2010-01-01

The evolutionary loss of hepatic urate oxidase (uricase) has resulted in humans with elevated serum uric acid (urate). Uricase loss may have been beneficial to early primate survival. However, an elevated serum urate has predisposed man to hyperuricemia, a metabolic disturbance leading to gout, hypertension, and various cardiovascular diseases. Human serum urate levels are largely determined by urate reabsorption and secretion in the kidney. Renal urate reabsorption is controlled via two proximal tubular urate transporters: apical URAT1 (SLC22A12) and basolateral URATv1/GLUT9 (SLC2A9). In contrast, the molecular mechanism(s) for renal urate secretion remain unknown. In this report, we demonstrate that an orphan transporter hNPT4 (human sodium phosphate transporter 4; SLC17A3) was a multispecific organic anion efflux transporter expressed in the kidneys and liver. hNPT4 was localized at the apical side of renal tubules and functioned as a voltage-driven urate transporter. Furthermore, loop diuretics, such as furosemide and bumetanide, substantially interacted with hNPT4. Thus, this protein is likely to act as a common secretion route for both drugs and may play an important role in diuretics-induced hyperuricemia. The in vivo role of hNPT4 was suggested by two hyperuricemia patients with missense mutations in SLC17A3. These mutated versions of hNPT4 exhibited reduced urate efflux when they were expressed in Xenopus oocytes. Our findings will complete a model of urate secretion in the renal tubular cell, where intracellular urate taken up via OAT1 and/or OAT3 from the blood exits from the cell into the lumen via hNPT4. PMID:20810651

Acute gouty bursitis: report of 15 cases.

PubMed Central

Canoso, J J; Yood, R A

1979-01-01

Fifteen cases of acute gouty bursitis were seen among 136 crystal-proved cases of gout. Bursal aspirate yielded yellow or pink fluid in 10, chalky white fluid in 1, and a small amount of bloody fluid in 4. Monosodium urate crystals were present in all. Bursal fluid leucocyte counts averaged 2.9 X 10(9)/1 compared with synovial fluid leucocyte counts that averaged 25.5 X 10(9)/1 in cases of articular gout (P less than 0.05). Gouty, septic, and idiopathic (traumatic) bursitis share clinical features, and detailed bursal fluid analysis is crucial for diagnosis. PMID:496446

Microbial urate catabolism: characterization of HpyO, a non-homologous isofunctional isoform of the flavoprotein urate hydroxylase HpxO.

PubMed

Michiel, Magalie; Perchat, Nadia; Perret, Alain; Tricot, Sabine; Papeil, Aude; Besnard, Marielle; de Berardinis, Véronique; Salanoubat, Marcel; Fischer, Cécile

2012-12-01

In aerobic cells, urate is oxidized to 5-hydroxyisourate by two distinct enzymes: a coenzyme-independent urate oxidase (EC 1.7.3.3) found in eukaryotes and bacteria like Bacillus subtilis and a prokaryotic flavoprotein urate hydroxylase (HpxO) originally found in some Klebsiella species. More cases of analogous or non-homologous isofunctional enzymes (NISE) for urate catabolism have been hypothesized by inspecting bacterial genomes. Here, we used a functional complementation approach in which a candidate gene for urate oxidation is integrated by homologous recombination in the Acinetobacter baylyi ADP1 genome at the locus of its original hpxO gene. Catabolism of urate was restored in A. baylyi ADP1 expressing a FAD-dependent protein from Xanthomonas campestris, representing a new urate hydroxylase family that we called HpyO. This enzyme was kinetically characterized and compared with other HpxO enzymes. In contrast to the latter, HpyO is a typical Michaelian enzyme. This work provides the first experimental evidences for the function of HpyO in bacterial urate catabolism and establishes it as a NISE of HpxO. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

Models of globular proteins in aqueous solutions

NASA Astrophysics Data System (ADS)

Wentzel, Nathaniel James

Protein crystallization is a continuing area of research. Currently, there is no universal theory for the conditions required to crystallize proteins. A better understanding of protein crystallization will be helpful in determining protein structure and preventing and treating certain diseases. In this thesis, we will extend the understanding of globular proteins in aqueous solutions by analyzing various models for protein interactions. Experiments have shown that the liquid-liquid phase separation curves for lysozyme in solution with salt depend on salt type and salt concentration. We analyze a simple square well model for this system whose well depth depends on salt type and salt concentration, to determine the phase coexistence surfaces from experimental data. The surfaces, calculated from a single Monte Carlo simulation and a simple scaling argument, are shown as a function of temperature, salt concentration and protein concentration for two typical salts. Urate Oxidase from Asperigillus flavus is a protein used for studying the effects of polymers on the crystallization of large proteins. Experiments have determined some aspects of the phase diagram. We use Monte Carlo techniques and perturbation theory to predict the phase diagram for a model of urate oxidase in solution with PEG. The model used includes an electrostatic interaction, van der Waals attraction, and a polymerinduced depletion interaction. The results agree quantitatively with experiments. Anisotropy plays a role in globular protein interactions, including the formation of hemoglobin fibers in sickle cell disease. Also, the solvent conditions have been shown to play a strong role in the phase behavior of some aqueous protein solutions. Each has previously been treated separately in theoretical studies. Here we propose and analyze a simple, combined model that treats both anisotropy and solvent effects. We find that this model qualitatively explains some phase behavior, including the existence of a lower critical point under certain conditions.

Serum Urate at Trial Entry and ALS Progression in EMPOWER

PubMed Central

O'Reilly, Éilis J.; Liu, Dawei; Johns, Donald R.; Cudkowicz, Merit E.; Paganoni, Sabrina; Schwarzschild, Michael A.; Leitner, Melanie; Ascherio, Alberto

2017-01-01

Objective Determine whether serum urate predicts ALS progression. Methods The study population comprised adult participants of EMPOWER (n=942), a phase III clinical trial to evaluate the efficacy of dexpramipexole to treat ALS. Urate was measured in blood samples collected during enrollment as part of the routine block chemistry. Outcomes Combined assessment of function and survival rank (CAFs), and time to death, by 12 months. Results In women there was not a significant relation between urate and outcomes. In men, outcomes improved with increasing urate (comparing highest to lowest urate quartile: CAFS was 53 points better with p for trend=0.04; and hazard ratio for death was 0.60 with p for trend=0.07), but with adjustment for body mass index (BMI) at baseline, a predictor of both urate levels and prognosis, associations were attenuated and no longer statistically significant. Overall, participants with urate levels equal to or above the median (5.1 mg/dL) appeared to have a survival advantage compared to those below (hazard ratio adjusted for BMI: 0.67; 95% confidence interval: 0.47 to 0.95). Conclusion These findings suggest that while the association between urate at baseline and ALS progression is partially explained by BMI, there may be an independent beneficial effect of urate. PMID:27677562

Effect of pyrazinamide and probenecid on peritoneal urate transport kinetics during continuous ambulatory peritoneal dialysis.

PubMed

Spaia, S; Magoula, I; Tsapas, G; Vayonas, G

2000-01-01

We administered pyrazinamide (PZA) and probenecid (PB) --two well-known modulators of urate transport via the proximal tubules - to evaluate their impact on urate transport through the peritoneal membrane and to clarify mechanisms affecting peritoneal transport. A continuous ambulatory peritoneal dialysis (CAPD) unit in 2nd Hospital of IKA (Social Services Institute), Greece. In 20 stable CAPD patients, on the study day, a 4-hour, 2-L, 1.36% glucose exchange was performed (control exchange). Pyrazinamide 3 g was given orally and another identical exchange was performed (study exchange). The same protocol was repeated with 2 g PB. KtN, peritoneal clearances of urea, creatinine, and urate for each exchange, and mass transfer area coefficients (MTAC) for the three solutes and their dialysate-to-plasma concentration (D/P) ratios were used to estimate peritoneal transport. Administration of PZA resulted in decreased clearances and MTAC values for the three solutes. The D/P ratio decreased significantly only for urate, indicating a more intense influence of PZA on urate. After PB administration, clearances of urea, creatinine, and urate were increased. MTAC and DIP ratio increased significantly only for urate (p < 0.05), demonstrating an action similar to that exerted on renal tubules. These findings provide evidence that unrestricted diffusion is not the only transport mechanism in the case of urate, and demonstrate the existence of an active mechanism in peritoneal urate transport with a reabsorptive and, probably, a secretive component that resembles that of renal tubule urate transport. Attention should be given in the case of CAPD patients undergoing antituberculous (PZA) treatment: it might have a negative impact on urea, creatinine, and urate peritoneal transport rates.

Anti- and pro-oxidant effects of quercetin in copper-induced low density lipoprotein oxidation. Quercetin as an effective antioxidant against pro-oxidant effects of urate.

PubMed

Filipe, Paulo; Haigle, Josiane; Silva, João Nuno; Freitas, João; Fernandes, Afonso; Mazière, Jean-Claude; Mazière, Cécile; Santus, René; Morlière, Patrice

2004-05-01

We recently reported that, depending on its concentration, urate is either a pro- or an antioxidant in Cu(2+)-induced low-density lipoprotein (LDL) oxidation. We also previously demonstrated an antioxidant synergy between urate and some flavonoids in the Cu(2+)-induced oxidation of diluted serum. As a result, the effect of the flavonoid quercetin on the Cu(2+)-induced oxidation of isolated LDL has been studied either in the presence or absence of urate. We demonstrate that, like urate, quercetin alone, at low concentration, exhibits a pro-oxidant activity. The pro-oxidant behavior depends on the Cu(2+) concentration but it is not observed at high Cu(2+) concentration. When compared with urate, the switch between the pro- and the antioxidant activities occurs at much lower quercetin concentrations. As for urate, the pro-oxidant character of quercetin is related to its ability to reduce Cu(2+) with the formation of semioxidized quercetin and Cu(+) with an expected yield larger than that obtained with urate owing to a more favorable redox potential. It is also shown that the pro-oxidant activity of urate can be inhibited by quercetin. An electron transfer between quercetin and semioxidized urate leading to the repair of urate could account for this observation as suggested by recently published pulse radiolysis data. It is anticipated that the interactions between quercetin-Cu(2+)-LDL and urate, which are tightly controlled by their respective concentration, determine the balance between the pro- and antioxidant behaviors. Moreover, as already observed with other antioxidants, it is demonstrated that quercetin alone behaves as a pro-oxidant towards preoxidized LDL.

Recent advances on uric acid transporters

PubMed Central

Xu, Liuqing; Shi, Yingfeng; Zhuang, Shougang; Liu, Na

2017-01-01

Uric acid is the product of purine metabolism and its increased levels result in hyperuricemia. A number of epidemiological reports link hyperuricemia with multiple disorders, such as kidney diseases, cardiovascular diseases and diabetes. Recent studies also showed that expression and functional changes of urate transporters are associated with hyperuricemia. Uric acid transporters are divided into two categories: urate reabsorption transporters, including urate anion transporter 1 (URAT1), organic anion transporter 4 (OAT4) and glucose transporter 9 (GLUT9), and urate excretion transporetrs, including OAT1, OAT3, urate transporter (UAT), multidrug resistance protein 4 (MRP4/ABCC4), ABCG-2 and sodium-dependent phosphate transport protein. In the kidney, uric acid transporters decrease the reabsorption of urate and increase its secretion. These transporters’ dysfunction would lead to hyperuricemia. As the function of urate transporters is important to control the level of serum uric acid, studies on the functional role of uric acid transporter may provide a new strategy to treat hyperuricemia associated diseases, such as gout, chronic kidney disease, hyperlipidemia, hypertension, coronary heart disease, diabetes and other disorders. This review article summarizes the physiology of urate reabsorption and excretion transporters and highlights the recent advances on their roles in hyperuricemia and various diseases. PMID:29246027

Serum urate at trial entry and ALS progression in EMPOWER.

PubMed

O'Reilly, ÉIlis J; Liu, Dawei; Johns, Donald R; Cudkowicz, Merit E; Paganoni, Sabrina; Schwarzschild, Michael A; Leitner, Melanie; Ascherio, Alberto

2017-02-01

Our objective was to determine whether serum urate predicts ALS progression. A study population comprised adult participants of EMPOWER (n = 942), a phase III clinical trial to evaluate the efficacy of dexpramipexole to treat ALS. Urate was measured in blood samples collected during enrollment as part of the routine block chemistry. We measured outcomes by combined assessment of function and survival rank (CAFs), and time to death, by 12 months. Results showed that in females there was not a significant relation between urate and outcomes. In males, outcomes improved with increasing urate (comparing highest to lowest urate quartile: CAFS was 53 points better with p for trend = 0.04; and hazard ratio for death was 0.60 with p for trend = 0.07), but with adjustment for body mass index (BMI) at baseline, a predictor of both urate levels and prognosis, associations were attenuated and no longer statistically significant. Overall, participants with urate levels equal to or above the median (5.1 mg/dl) appeared to have a survival advantage compared to those below (hazard ratio adjusted for BMI: 0.67; 95% confidence interval 0.47-0.95). In conclusion, these findings suggest that while the association between urate at baseline and ALS progression is partially explained by BMI, there may be an independent beneficial effect of urate.

A novel three-dimensional large-pore mesoporous carbon matrix as a potential nanovehicle for the fast release of the poorly water-soluble drug, celecoxib.

PubMed

Zhang, Yanzhuo; Wang, Hong; Li, Chuanjun; Sun, Baoxiang; Wang, Yu; Wang, Siling; Gao, Cunqiang

2014-04-01

A novel mesocellular carbon foam (MSU-FC) with a large pore size and a three-dimensional porous structure for the oral delivery of poorly water-soluble drugs was prepared. The goal of this study was to improve in vitro dissolution and in vivo absorption of celecoxib (CEB), a model drug, by means of novel carbon-based nanoparticles prepared from the MSU-FC matrix. The MSU-FC matrix was synthesized by an inverse replica templating method using mesocellular silica template. A solvent immersion/evaporation method was used to load the drug molecules. The drug-loaded nanoparticles were characterized for morphology, surface area, particle size, mesoporous structure, crystallinity, solubility and dissolution. The effect of MSU-FC on cell viability was measured using the MTT conversion assay. Furthermore, the oral bioavailability of CEB-loaded MSU-FC in fasted rats was compared with that of the marketed product. Our results demonstrate that CEB incorporation into the prepared MSU-FC resulted in an approximately 9-fold increase in aqueous solubility in comparison with crystalline CEB. MSU-FC produced accelerated immediate release of CEB in comparison with crystalline CEB (pure CEB powder or marketed formulation) and the drug-loaded conventional mesoporous carbon particles. The relative bioavailability of CEB for CEB-loaded MSU-FC was 172%. In addition, MSU-FC nanoparticles exhibited very low toxicity. The MSU-FC nanomatrix has been shown to be a promising drug delivery vehicle for improving the dissolution and biopharmaceutical characteristics of poorly water-soluble drugs.

Synthesis and characterization of Cr-MSU-1 and its catalytic application for oxidation of styrene

NASA Astrophysics Data System (ADS)

Liu, Hong; Wang, Zhigang; Hu, Hongjiu; Liang, Yuguang; Wang, Mengyang

2009-07-01

Chromium-containing mesoporous silica material Cr-MSU-1 was synthesized using lauryl alcohol-polyoxyethylene (23) ether as templating agent under the neutral pH condition by two-step method. The sample was characterized by XRD, TEM, FT-IR, UV-Vis, ESR, ICP-AES and N 2 adsorption. Its catalytic performance for oxidation of styrene was studied. Effects of the solvent used, the styrene/H 2O 2 mole ratio and the reaction temperature and time on the oxidation of styrene over the Cr-MSU-1 catalyst were examined. The results indicate that Cr ions have been successfully incorporated into the framework of MSU-1 and the Cr-MSU-1 material has a uniform worm-like holes mesoporous structure. After Cr-MSU-1 is calcined, most of Cr 3+ is oxidized to Cr 5+ and Cr 6+ in tetrahedral coordination and no extra-framework Cr 2O 3 is formed. The Cr-MSU-1 catalyst is highly active for the selective oxidation of styrene and the main reaction products over Cr-MSU-1 are benzaldehyde and phenylacetaldehyde. Its catalytic performance remains stable within five repeated runs and no leaching is noticed for this chromium-based catalyst.

Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

PubMed Central

Köttgen, Anna; Albrecht, Eva; Teumer, Alexander; Vitart, Veronique; Krumsiek, Jan; Hundertmark, Claudia; Pistis, Giorgio; Ruggiero, Daniela; O’Seaghdha, Conall M; Haller, Toomas; Yang, Qiong; Tanaka, Toshiko; Johnson, Andrew D; Kutalik, Zoltán; Smith, Albert V; Shi, Julia; Struchalin, Maksim; Middelberg, Rita P S; Brown, Morris J; Gaffo, Angelo L; Pirastu, Nicola; Li, Guo; Hayward, Caroline; Zemunik, Tatijana; Huffman, Jennifer; Yengo, Loic; Zhao, Jing Hua; Demirkan, Ayse; Feitosa, Mary F; Liu, Xuan; Malerba, Giovanni; Lopez, Lorna M; van der Harst, Pim; Li, Xinzhong; Kleber, Marcus E; Hicks, Andrew A; Nolte, Ilja M; Johansson, Asa; Murgia, Federico; Wild, Sarah H; Bakker, Stephan J L; Peden, John F; Dehghan, Abbas; Steri, Maristella; Tenesa, Albert; Lagou, Vasiliki; Salo, Perttu; Mangino, Massimo; Rose, Lynda M; Lehtimäki, Terho; Woodward, Owen M; Okada, Yukinori; Tin, Adrienne; Müller, Christian; Oldmeadow, Christopher; Putku, Margus; Czamara, Darina; Kraft, Peter; Frogheri, Laura; Thun, Gian Andri; Grotevendt, Anne; Gislason, Gauti Kjartan; Harris, Tamara B; Launer, Lenore J; McArdle, Patrick; Shuldiner, Alan R; Boerwinkle, Eric; Coresh, Josef; Schmidt, Helena; Schallert, Michael; Martin, Nicholas G; Montgomery, Grant W; Kubo, Michiaki; Nakamura, Yusuke; Tanaka, Toshihiro; Munroe, Patricia B; Samani, Nilesh J; Jacobs, David R; Liu, Kiang; D’Adamo, Pio; Ulivi, Sheila; Rotter, Jerome I; Psaty, Bruce M; Vollenweider, Peter; Waeber, Gerard; Campbell, Susan; Devuyst, Olivier; Navarro, Pau; Kolcic, Ivana; Hastie, Nicholas; Balkau, Beverley; Froguel, Philippe; Esko, Tõnu; Salumets, Andres; Khaw, Kay Tee; Langenberg, Claudia; Wareham, Nicholas J; Isaacs, Aaron; Kraja, Aldi; Zhang, Qunyuan; Wild, Philipp S; Scott, Rodney J; Holliday, Elizabeth G; Org, Elin; Viigimaa, Margus; Bandinelli, Stefania; Metter, Jeffrey E; Lupo, Antonio; Trabetti, Elisabetta; Sorice, Rossella; Döring, Angela; Lattka, Eva; Strauch, Konstantin; Theis, Fabian; Waldenberger, Melanie; Wichmann, H-Erich; Davies, Gail; Gow, Alan J; Bruinenberg, Marcel; Study, LifeLines Cohort; Stolk, Ronald P; Kooner, Jaspal S; Zhang, Weihua; Winkelmann, Bernhard R; Boehm, Bernhard O; Lucae, Susanne; Penninx, Brenda W; Smit, Johannes H; Curhan, Gary; Mudgal, Poorva; Plenge, Robert M; Portas, Laura; Persico, Ivana; Kirin, Mirna; Wilson, James F; Leach, Irene Mateo; van Gilst, Wiek H; Goel, Anuj; Ongen, Halit; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G; Imboden, Medea; von Eckardstein, Arnold; Cucca, Francesco; Nagaraja, Ramaiah; Piras, Maria Grazia; Nauck, Matthias; Schurmann, Claudia; Budde, Kathrin; Ernst, Florian; Farrington, Susan M; Theodoratou, Evropi; Prokopenko, Inga; Stumvoll, Michael; Jula, Antti; Perola, Markus; Salomaa, Veikko; Shin, So-Youn; Spector, Tim D; Sala, Cinzia; Ridker, Paul M; Kähönen, Mika; Viikari, Jorma; Hengstenberg, Christian; Nelson, Christopher P; Consortium, CARDIoGRAM; Consortium, DIAGRAM; Consortium, ICBP; Consortium, MAGIC; Meschia, James F; Nalls, Michael A; Sharma, Pankaj; Singleton, Andrew B; Kamatani, Naoyuki; Zeller, Tanja; Burnier, Michel; Attia, John; Laan, Maris; Klopp, Norman; Hillege, Hans L; Kloiber, Stefan; Choi, Hyon; Pirastu, Mario; Tore, Silvia; Probst-Hensch, Nicole M; Völzke, Henry; Gudnason, Vilmundur; Parsa, Afshin; Schmidt, Reinhold; Whitfield, John B; Fornage, Myriam; Gasparini, Paolo; Siscovick, David S; Polašek, Ozren; Campbell, Harry; Rudan, Igor; Bouatia-Naji, Nabila; Metspalu, Andres; Loos, Ruth J F; van Duijn, Cornelia M; Borecki, Ingrid B; Ferrucci, Luigi; Gambaro, Giovanni; Deary, Ian J; Wolffenbuttel, Bruce H R; Chambers, John C; März, Winfried; Pramstaller, Peter P; Snieder, Harold; Gyllensten, Ulf; Wright, Alan F; Navis, Gerjan; Watkins, Hugh; Witteman, Jacqueline C M; Sanna, Serena; Schipf, Sabine; Dunlop, Malcolm G; Tönjes, Anke; Ripatti, Samuli; Soranzo, Nicole; Toniolo, Daniela; Chasman, Daniel I; Raitakari, Olli; Kao, W H Linda; Ciullo, Marina; Fox, Caroline S; Caulfield, Mark; Bochud, Murielle; Gieger, Christian

2013-01-01

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout. PMID:23263486

The Association of Dietary Intake of Purine-Rich Vegetables, Sugar-Sweetened Beverages and Dairy with Plasma Urate, in a Cross-Sectional Study

PubMed Central

Zgaga, Lina; Theodoratou, Evropi; Kyle, Janet; Farrington, Susan M.; Agakov, Felix; Tenesa, Albert; Walker, Marion; McNeill, Geraldine; Wright, Alan F.; Rudan, Igor; Dunlop, Malcolm G.; Campbell, Harry

2012-01-01

Introduction Hyperuricemia is a strong risk factor for gout. The incidence of gout and hyperuricemia has increased recently, which is thought to be, in part, due to changes in diet and lifestyle. Objective of this study was to investigate the association between plasma urate concentration and: a) food items: dairy, sugar-sweetened beverages (SSB) and purine-rich vegetables; b) related nutrients: lactose, calcium and fructose. Methods A total of 2,076 healthy participants (44% female) from a population-based case-control study in Scotland (1999–2006) were included in this study. Dietary data was collected using a semi-quantitative food frequency questionnaire (FFQ). Nutrient intake was calculated using FFQ and composition of foods information. Urate concentration was measured in plasma. Results Mean urate concentration was 283.8±72.1 mmol/dL (females: 260.1±68.9 mmol/dL and males: 302.3±69.2 mmol/dL). Using multivariate regression analysis we found that dairy, calcium and lactose intakes were inversely associated with urate (p = 0.008, p = 0.003, p = 0.0007, respectively). Overall SSB consumption was positively associated with urate (p = 0.008), however, energy-adjusted fructose intake was not associated with urate (p = 0.66). The intake of purine-rich vegetables was not associated to plasma urate (p = 0.38). Conclusions Our results suggest that limiting purine-rich vegetables intake for lowering plasma urate may be ineffectual, despite current recommendations. Although a positive association between plasma urate and SSB consumption was found, there was no association with fructose intake, suggesting that fructose is not the causal agent underlying the SSB-urate association. The abundant evidence supporting the inverse association between plasma urate concentration and dairy consumption should be reflected in dietary guidelines for hyperuricemic individuals and gout patients. Further research is needed to establish which nutrients and food products influence plasma urate concentration, to inform the development of evidence-based dietary guidelines. PMID:22701608

Gout - a guide for the general and acute physicians.

PubMed

Abhishek, Abhishek; Roddy, Edward; Doherty, Michael

2017-02-01

Gout is the most prevalent inflammatory arthritis and affects 2.5% of the general population in the UK. It is also the only arthritis that has the potential to be cured with safe, inexpensive and well tolerated urate-lowering treatments, which reduce serum uric acid by either inhibiting xanthine oxidase - eg allopurinol, febuxostat - or by increasing the renal excretion of uric acid. Of these, xanthine oxidase inhibitors are used first line and are effective in 'curing' gout in the vast majority of patients. Gout can be diagnosed on clinical grounds in those with typical podagra. However, in those with involvement of other joints, joint aspiration is recommended to demonstrate monosodium urate crystals and exclude other causes of acute arthritis, such as septic arthritis. However, a clinical diagnosis of gout can be made if joint aspiration is not feasible. This review summarises the current understanding of the pathophysiology, clinical presentation, investigations and treatment of gout. © Royal College of Physicians 2017. All rights reserved.

Protective effects of Cinnamomum cassia (Lamaceae) against gout and septic responses via attenuation of inflammasome activation in experimental models.

PubMed

Shin, Woo-Young; Shim, Do-Wan; Kim, Myong-Ki; Sun, Xiao; Koppula, Sushruta; Yu, Sang-Hyeun; Kim, Han-Bi; Kim, Tack-Joong; Kang, Tae-Bong; Lee, Kwang-Ho

2017-06-09

Cinnamomum cassia (C. cassia, Lauraceae family), commonly used for treating dyspepsia, gastritis, blood circulation, and inflammatory diseases is considered as one of the 50 fundamental herbs in traditional Chinese medicine. The anti-inflammatory action of an ethanol extract of C. cassia (CA), and its underlying mechanisms were explored in both in vitro cellular and in vivo murine models. Bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of CA on inflammasome activation. A lipopolysaccharide (LPS)-induced sepsis mouse model and a monosodium urate (MSU)-induced gout model were employed to study the effect of CA on in vivo efficacy. CA improved the survival rate in the LPS-induced septic shock mouse model and inhibited inflammasome activation including NLRP3, NLRC4, and AIM2, leading to suppression of interleukin-1β secretion. Further, ASC oligomerization and its speck formation in cytosol were attenuated by CA treatment. Furthermore, CA improved both survival rate of LPS-induced septic shock and gout murine model. CA treatment significantly attenuated danger signals-induced inflammatory responses via regulation of inflammasome activation, substantiating the traditional claims of its use in the treatment of inflammation-related disorders. Copyright © 2017. Published by Elsevier B.V.

Urate is a ligand for the transcriptional regulator PecS.

PubMed

Perera, Inoka C; Grove, Anne

2010-09-24

PecS is a member of the MarR (multiple antibiotic resistance regulator) family, which has been shown in Erwinia to regulate the expression of virulence genes. MarR homologs typically bind a small molecule ligand, resulting in attenuated DNA binding. For PecS, the natural ligand has not been identified. We have previously shown that urate is a ligand for the Deinococcus radiodurans-encoded MarR homolog HucR (hypothetical uricase regulator) and identified residues responsible for ligand binding. We show here that all four residues involved in urate binding and propagation of conformational changes to DNA recognition helices are conserved in PecS homologs, suggesting that urate is the ligand for PecS. Consistent with this prediction, Agrobacterium tumefaciens PecS specifically binds urate, and urate attenuates DNA binding in vitro. PecS binds two operator sites in the intergenic region between the divergent pecS gene and pecM genes, one of which features two partially overlapping repeats to which PecS binds as a dimer on opposite faces of the duplex. Notably, urate dissociates PecS from cognate DNA, allowing transcription of both genes in vivo. Taken together, our data show that urate is a ligand for PecS and suggest that urate serves a novel function in signaling the colonization of a host plant. Copyright © 2010 Elsevier Ltd. All rights reserved.

Heat Stress Nephropathy From Exercise-Induced Uric Acid Crystalluria: A Perspective on Mesoamerican Nephropathy.

PubMed

Roncal-Jimenez, Carlos; García-Trabanino, Ramón; Barregard, Lars; Lanaspa, Miguel A; Wesseling, Catharina; Harra, Tamara; Aragón, Aurora; Grases, Felix; Jarquin, Emmanuel R; González, Marvin A; Weiss, Ilana; Glaser, Jason; Sánchez-Lozada, Laura G; Johnson, Richard J

2016-01-01

Mesoamerican nephropathy (MeN), an epidemic in Central America, is a chronic kidney disease of unknown cause. In this article, we argue that MeN may be a uric acid disorder. Individuals at risk for developing the disease are primarily male workers exposed to heat stress and physical exertion that predisposes to recurrent water and volume depletion, often accompanied by urinary concentration and acidification. Uric acid is generated during heat stress, in part consequent to nucleotide release from muscles. We hypothesize that working in the sugarcane fields may result in cyclic uricosuria in which uric acid concentrations exceed solubility, leading to the formation of dihydrate urate crystals and local injury. Consistent with this hypothesis, we present pilot data documenting the common presence of urate crystals in the urine of sugarcane workers from El Salvador. High end-of-workday urinary uric acid concentrations were common in a pilot study, particularly if urine pH was corrected to 7. Hyperuricemia may induce glomerular hypertension, whereas the increased urinary uric acid may directly injure renal tubules. Thus, MeN may result from exercise and heat stress associated with dehydration-induced hyperuricemia and uricosuria. Increased hydration with water and salt, urinary alkalinization, reduction in sugary beverage intake, and inhibitors of uric acid synthesis should be tested for disease prevention. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Fourier transform infrared spectroscopy for analysis of kidney stones.

PubMed

Khan, Aysha Habib; Imran, Sheharbano; Talati, Jamsheer; Jafri, Lena

2018-01-01

To compare the results of a chemical method of kidney stone analysis with the results of Fourier transform infrared (FT-IR) spectroscopy. Kidney stones collected between June and October 2015 were simultaneously analyzed by chemical and FT-IR methods. Kidney stones (n=449) were collected from patients from 1 to 81 years old. Most stones were from adults, with only 11.5% from children (aged 3-16 years) and 1.5% from children aged <2 years. The male to female ratio was 4.6. In adults, the calcium oxalate stone type, calcium oxalate monohydrate (COM, n=224), was the most common crystal, followed by uric acid and calcium oxalate dihydrate (COD, n=83). In children, the most frequently occurring type was predominantly COD (n=21), followed by COM (n=11), ammonium urate (n=10), carbonate apatite (n=6), uric acid (n=4), and cystine (n=1). Core composition in 22 stones showed ammonium urate (n=2), COM (n=2), and carbonate apatite (n=1) in five stones, while uric acid crystals were detected (n=13) by FT-IR. While chemical analysis identified 3 stones as uric acid and the rest as calcium oxalate only. Agreement between the two methods was moderate, with a kappa statistic of 0.57 (95% confidence interval, 0.5-0.64). Disagreement was noted in the analysis of 77 stones. FT-IR analysis of kidney stones can overcome many limitations associated with chemical analysis.

Feline urate urolithiasis.

PubMed

Appel, Sherry L; Houston, Doreen M; Moore, Andrew E P; Weese, J Scott

2010-05-01

This retrospective case control study describes associations between feline urate urolithiasis and breed, age, gender, and urine composition. Data from cases of feline uroliths submitted to the Canadian Veterinary Urolith Centre (CVUC) between February 2, 1998 and July 7, 2007 were reviewed. There were 10 083 feline uroliths examined, including 385 ammonium urate, 13 uric acid, and 21 mixed struvite/urate uroliths. The Egyptian Mau, Birman, and Siamese breeds were significantly predisposed to urate urolithiasis [odds ratio (OR) = 118, 95% confidence interval (CI) = 38.2 to 510, P < 0.001], (OR = 9.1, 95% CI = 2.0 to 32, P < 0.001) and (OR = 3.9, 95% CI = 2.5 to 5.9, P < 0.001), respectively. Urate urolithiasis was more frequent in younger cats (mean age 6.3 versus 7.1 y in cats with other uroliths, P < 0.0001) and in male cats (P = 0.024). The association between Egyptian Maus and urate urolithiasis was remarkable. The association in Siamese cats is consistent with prior reports, and the association with Birman cats requires further study.

Nano-graphite functionalized mesocellular carbon foam with enhanced intra-penetrating electrical percolation networks for high performance electrochemical energy storage electrode materials.

PubMed

Jo, Changshin; An, Sunhyung; Kim, Younghoon; Shim, Jongmin; Yoon, Songhun; Lee, Jinwoo

2012-04-28

Mesocellular carbon foam (MSU-F-C) is functionalized with hollow nanographite by a simple solution-phase method to enhance the intrapenetrating electrical percolation network. The electrical conductivity of the resulting material, denoted as MSU-F-C-G, is increased by a factor of 20.5 compared with the pristine MSU-F-C. Hollow graphite nanoparticles are well-dispersed in mesocellular carbon foam, as confirmed by transmission electron microscopy (TEM), and the d spacing of the (002) planes is 0.343 nm, which is only slightly larger than that of pure graphite (0.335 nm), suggesting a random combination of graphitic and turbostratic stacking. After nanographitic functionalization, the BET surface area and total pore volume decreased from 928 m(2) g(-1) and 1.5 cm(3) g(-1) to 394 m(2) g(-1) and 0.7 cm(3) g(-1), respectively. Thermogravimetric analysis in air shows that the thermal stability of MSU-F-C-G is improved relative to that of MSU-F-C, and the one-step weight loss indicates that the nanographite is homogeneously functionalized on the MSU-F-C particles. When the resulting mesocellular carbon materials are used as electrode materials for an electric double layer capacitor (EDLC), the specific capacitances (C(sp)) of the MSU-F-C and MSU-F-C-G electrodes at 4 mV s(-1) are 109 F g(-1) and 93 F g(-1), respectively. The MSU-F-C-G electrode exhibited a very high area capacitance (C(area), 23.5 μF cm(-2)) compared with that of the MSU-F-C electrode (11.7 μF cm(-2)), which is attributed to the enhanced intraparticle conductivity by the nanographitic functionalization. MSU-F-C-G exhibited high capacity retention (52%) at a very high scan rate of 512 mV s(-1), while only a 23% capacity retention at 512 mV s(-1) was observed in the case of the MSU-F-C electrode. When applied as an anode in a lithium ion battery, a significant increase in the initial efficiency (44%), high reversible discharge capacity (580 mA h g(-1)) in the lower voltage region, and a higher rate capability were observed. The high rate capability of the MSU-F-C-G electrode as charge storage was due to the low resistance derived from the nanographitic functionalization. This journal is © the Owner Societies 2012

A pilot study: sodium urate synovitis as an acute model of inflammatory response using objective and subjective criteria to evaluate arthritic pain in cats.

PubMed

Carroll, G L; Narbe, R; Peterson, K; Kerwin, S C; Taylor, L; DeBoer, M

2008-10-01

Sodium urate (SU) synovitis was evaluated as a model for feline arthritic pain using a placebo- and positive-controlled (meloxicam) randomized blinded controlled single crossover design. Monosodium urate crystals [20 mg (1 mL) rod-shaped] were injected into alternate stifles of trained anesthetized cats (n = 3) with a 28 day washout. During the first trial phase, two cats received meloxicam (0.1 mg/kg, PO), a nonsteroidal anti-inflammatory drug (NSAID), for three days before and on the day of SU injection; the third cat received placebo. Treatments and stifles were switched for the second trial. Total force, contact pressure and area of the fore and hind limbs were measured using a pressure mat one day and 0.5 h before, and 2, 4, 6, 8, 10, 24, and 30 h post-SU injection. Skin temperature, joint circumference, analgesia, lameness, and visual analogue scale (VAS) pain scores, were measured at the same times. Comparisons were made for each time and for areas under the curve (AUC) using original and change from baseline; P < 0.05 was significant. Significant differences in force mat data and subjective data were found for the hind limb data (total force and total contact pressure at 6, 10, and 30 h; analgesia and VAS for pain at 4 h; lameness at 10, 24, and 30 h) and for AUC(0)-->(24h) and AUC(0)-->(30 h) (total force, total contact pressure, and mean lameness score) and for differences from BL AUC(0)-->(10h) (total contact area) and AUC(0)-->(24h) (total contact area and mean lameness score) and AUC(0)-->(30 h) (total force, total contact area, and mean lameness). No cats required rescue analgesia. Injection of 1 mL of monosodium urate into the stifle of a cat causes moderate transitory pain and was suitable for assessing analgesic efficacy of an NSAID with a pressure mat and subjective criteria.

Up-titration of allopurinol in patients with gout.

PubMed

Jennings, Claudine G; Mackenzie, Isla S; Flynn, Rob; Ford, Ian; Nuki, George; De Caterina, Raffaele; Riches, Philip L; Ralston, Stuart H; MacDonald, Thomas M

2014-08-01

European League against Rheumatism (EULAR) gout management guidelines recommend achieving a target urate level <6.0 mg/dL (<357 µmol/L). Allopurinol is the most widely used urate-lowering therapy; however, many gout patients who are prescribed allopurinol do not have urate levels optimally controlled. The objective of this analysis was to review the efficacy and tolerability of allopurinol up-titration in achieving the EULAR target levels. The Febuxostat versus Allopurinol Streamlined Trial (FAST) is an ongoing multi-centre study comparing the cardiovascular safety of febuxostat and allopurinol (target recruitment: 5706 patients). Recruited patients were already taking allopurinol and the protocol required up-titration of daily allopurinol dose, in 100 mg increments, to achieve the EULAR urate target level prior to randomisation. We reviewed pre-randomisation data from the first 400 recruited and subsequently randomised FAST patients. Of 400 patients, 144 (36%) had urate levels ≥357 µmol/L at screening and required allopurinol up-titration. Higher urate levels were significantly associated with lower allopurinol dose, male sex, increased BMI, increased alcohol intake and diuretic use. Mean fall in urate levels after a single 100-mg dose increase was 71 µmol/L. The number of up-titrations required ranged from one to five (median = 1) with 65% of patients controlled after one 100-mg up-titration. Overall, 97% of up-titrated patients achieved target urate levels with median final allopurinol dose of 300 mg daily. Side effects and complications of up-titration were minimal. Overall, 36% of FAST patients were not at target urate levels and required up-titration. Allopurinol up-titration was effective in achieving urate target levels and was generally well tolerated by patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Urate predicts rate of clinical decline in Parkinson disease

PubMed Central

Ascherio, Alberto; LeWitt, Peter A.; Xu, Kui; Eberly, Shirley; Watts, Arthur; Matson, Wayne R.; Marras, Connie; Kieburtz, Karl; Rudolph, Alice; Bogdanov, Mikhail B.; Schwid, Steven R.; Tennis, Marsha; Tanner, Caroline M.; Beal, M. Flint; Lang, Anthony E.; Oakes, David; Fahn, Stanley; Shoulson, Ira; Schwarzschild, Michael A.

2009-01-01

Context The risk of Parkinson disease (PD) and its rate of progression may decline with increasing blood urate, a major antioxidant. Objective To determine whether serum and cerebrospinal fluid (CSF) concentrations of urate predict clinical progression in patients with PD. Design, Setting, and Participants 800 subjects with early PD enrolled in the DATATOP trial. Pre-treatment urate was measured in serum for 774 subjects and in CSF for 713. Main Outcome Measures Treatment-, age- and sex-adjusted hazard ratios (HRs) for clinical disability requiring levodopa therapy, the pre-specified primary endpoint. Results The HR of progressing to endpoint decreased with increasing serum urate (HR for 1 standard deviation increase = 0.82; 95% CI = 0.73 to 0.93). In analyses stratified by α-tocopherol treatment (2,000 IU/day), a decrease in the HR for the primary endpoint was seen only among subjects not treated with α-tocopherol (HR = 0.75; 95% CI = 0.62 to 0.89, versus those treated HR = 0.90; 95% CI = 0.75 to 1.08). Results were similar for the rate of change in the United Parkinson Disease Rating Scale (UPDRS). CSF urate was also inversely related to both the primary endpoint (HR for highest versus lowest quintile = 0.65; 95% CI: 0.54 to 0.96) and to the rate of change in UPDRS. As with serum urate, these associations were present only among subjects not treated with α-tocopherol. Conclusion Higher serum and CSF urate at baseline were associated with slower rates of clinical decline. The findings strengthen the link between urate and PD and the rationale for considering CNS urate elevation as a potential strategy to slow PD progression. PMID:19822770

GLUT9 influences uric acid concentration in patients with Lesch-Nyhan disease.

PubMed

Torres, Rosa J; Puig, Juan G

2018-06-01

Patients with deficient hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity present hyperuricemia and/or hyperuricosuria, with a variable degree of neurological manifestations. Hyperuricemia in HPRT deficiency is due to uric acid overproduction and is frequently treated with allopurinol. Renal uric acid excretion is sharply increased in these patients. In recent years, several renal tubular urate transporter single nucleotide polymorphisms (SNPs), including those of the GLUT9, ABCG2 and URAT1 genes, have been described that influence the renal handling of uric acid and modulate serum urate levels. In the present study, we analyzed whether GLUT9, ABCG2 and URAT1 gene SNPs are able to influence uric acid levels and allopurinol response in patients with HPRT deficiency. Three SNPs, URAT1 rs11231825, GLUT9 rs16890979 and ABCG2 rs2231142, previously associated in our population with hyperuricemia and gout, were analyzed in 27 patients with HPRT deficiency treated with allopurinol for at least 5 years. Patients with HPRT deficiency having allele A of rs16890979 in the GLUT9 gene present with a lower serum urate concentration at diagnosis, before allopurinol treatment is instituted, and need lower allopurinol doses to maintain serum urate levels between 268 and 446 μmol/L (4.5 and 7.5 mg/dL). No relationship between rs2231142 in the ABCG2 gene or rs11231825 in the URAT1 gene and serum urate levels or allopurinol response was found in our patients with HPRT deficiency. GLUT9 SNPs influence the renal handling of uric acid and modulate serum urate levels and the response to treatment in patients with uric acid overproduction due to HPRT deficiency. © 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Saponins extracted from Dioscorea collettii rhizomes regulate the expression of urate transporters in chronic hyperuricemia rats.

PubMed

Zhu, Liran; Dong, Yifan; Na, Sha; Han, Ru; Wei, Chengyin; Chen, Guangliang

2017-09-01

The current study aimed to investigate whether the saponins, bioactive component of effects of D. collettii, could reduce the serum uric acid level in a hyperuricemic mouse via regulation of urate transporters. Chronic hyperuricemia model was established by combine administration of adenine (100mg/kg) and ethambutol (250mg/kg). In the model group, the serum uric acid (SUA), urine uric acid (UUA) volume, and 24-h UUA values increased significantly, while the uric acid clearance rate (CUr) and creatinine clearance rate (CCr) values decreased. Further, the model groups showed significantly lower expression of organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) and significantly higher expression of renal tubular urate transporter 1 (URAT1), glucose transporter 9 (GLUT9) and URAT1 mRNA than the normal control group. Saponins administration was found to have a dose-dependent effect, as evidenced by the increase in the 24-h UUA, CUr and CCr values; the decrease in SUA; the decrease in the renal expression of URAT1 mRNA and URAT1 and GLUT9 proteins; and the increase in the renal expression of the OAT1 and OAT3 proteins. The saponins extracted from D. collettii rhizomes had an obvious anti-hyperuricemic effect through downregulation of the URAT1 mRNA and the URAT1 and GLUT9 proteins and upregulation of the OAT1 and OAT3 proteins. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Pre-diagnostic plasma urate and the risk of amyotrophic lateral sclerosis.

PubMed

O'Reilly, Éilis J; Bjornevik, Kjetil; Schwarzschild, Michael A; McCullough, Marjorie L; Kolonel, Laurence N; Le Marchand, Loic; Manson, Joann E; Ascherio, Alberto

2018-05-01

To prospectively examine for the first time the association between plasma urate levels measured in healthy participants and future amyotrophic lateral sclerosis (ALS) risk. A pooled case-control study nested in five US prospective cohorts comprising 319,617 participants who provided blood, of which 275 had ALS during follow-up. Pre-diagnostic plasma urate was determined for all participants using a clinical colorimetric enzyme assay. Gender-specific multivariable-adjusted rate ratios (RR) of ALS incidence or death estimated by conditional logistic regression and pooled using inverse-variance weighting. In age- and matching factor-adjusted analyses, a 1 mg/dL increase in urate concentration was associated with RR = 0.88 (95% CI: [0.78, 0.997] p = 0.044). After adjustment for BMI, a strong predictor of ALS and urate levels, and other potential covariates, the RR = 0.89 (95% CI: [0.78, 1.02]; p = 0.08 for 1mg/dL increase in urate). Elevation of plasma urate was modestly inversely associated with the risk of ALS and warrants further study for a potential role in this disease.

URAT South Parallax Results

NASA Astrophysics Data System (ADS)

Finch, Charlie T.; Zacharias, Norbert; Jao, Wei-Chun

2018-04-01

We present 916 trigonometric parallaxes and proper motions of newly discovered nearby stars from the United States Naval Observatory Robotic Astrometric Telescope (URAT). Observations were taken at the Cerro Tololo Interamerican Observatory over a 2-year period from 2015 to 2017 October covering the entire sky south of about +25° decl. SPM4 and UCAC4 early epoch catalog data were added to extend the temporal coverage for the parallax and proper motion fit up to 48 years. Using these new URAT parallaxes, optical and near-IR photometry from the AAVSO Photometric All-Sky Survey and Two Micron All-Sky Survey catalogs, we identify possible new nearby dwarfs, young stars, low-metallicity subdwarfs and white dwarfs. Comparison to known trigonometric parallaxes shows a high quality of the URAT-based results confirming the error in parallax of the URAT south parallaxes reported here to be between 2 and 13 mas. We also include additional 729 trigonometric parallaxes from the URAT north 25 pc sample published in Finch & Zacharias here after applying the same criterion as for the southern sample to have a complete URAT 25 pc sample presented in this paper.

Registration of ‘Coral’ Wheat

USDA-ARS?s Scientific Manuscript database

‘Coral’ soft white winter wheat (Triticum aestivum L.) was developed by the Michigan Agricultural Experiment Station and released March 28, 2008, via an exclusive licensing agreement through Michigan State University (MSU) Technologies. Coral was selected from the cross MSU D3913 / MSU D0331 made i...

Cooperative Extension as a Framework for Health Extension: The Michigan State University Model.

PubMed

Dwyer, Jeffrey W; Contreras, Dawn; Eschbach, Cheryl L; Tiret, Holly; Newkirk, Cathy; Carter, Erin; Cronk, Linda

2017-10-01

The Affordable Care Act charged the Agency for Healthcare Research and Quality to create the Primary Care Extension Program, but did not fund this effort. The idea to work through health extension agents to support health care delivery systems was based on the nationally known Cooperative Extension System (CES). Instead of creating new infrastructure in health care, the CES is an ideal vehicle for increasing health-related research and primary care delivery. The CES, a long-standing component of the land-grant university system, features a sustained infrastructure for providing education to communities. The Michigan State University (MSU) Model of Health Extension offers another means of developing a National Primary Care Extension Program that is replicable in part because of the presence of the CES throughout the United States. A partnership between the MSU College of Human Medicine and MSU Extension formed in 2014, emphasizing the promotion and support of human health research. The MSU Model of Health Extension includes the following strategies: building partnerships, preparing MSU Extension educators for participation in research, increasing primary care patient referrals and enrollment in health programs, and exploring innovative funding. Since the formation of the MSU Model of Health Extension, researchers and extension professionals have made 200+ connections, and grants have afforded savings in salary costs. The MSU College of Human Medicine and MSU Extension partnership can serve as a model to promote health partnerships nationwide between CES services within land-grant universities and academic health centers or community-based medical schools.

A network pharmacology approach to determine active ingredients and rationality of herb combinations of Modified-Simiaowan for treatment of gout.

PubMed

Zhao, Fangli; Guochun, Li; Yang, Yanhua; Shi, Le; Xu, Li; Yin, Lian

2015-06-20

Modified Simiaowan (MSW) is a traditional Chinese medicine (TCM) formula and is widely used as a clinically medication formula for its efficiency in treating gouty diseases.To predict the active ingredients in MSW and uncover the rationality of herb combinations of MSW. Three drug-target networks including the "candidate ingredient-target network" (cI-cT) that links the candidate ingredients and targets, the "core ingredient-target-pathway network" connecting core potential ingredients and targets through related pathways, and the "rationality of herb combinations of MSW network", which was derived from the cI-cT network, were developed to dissect the active ingredients in MSW and relationship between ingredients in herb combinations and their targets for gouty diseases. On the other hand, herbal ingredients comparisons were also conducted based on six physicochemical properties to investigate whether the herbs in MSW are similar in chemicals. Moreover, HUVEC viability and expression levels of ICAM-1 induced by monosodium urate (MSU) crystals were assessed to determine the activities of potential ingredients in MSW. Predicted by the core ingredient-target-pathway network, we collected 30 core ingredients in MSW and 25 inflammatory cytokines and uric acid synthetase or transporters, which are effective for gouty treatment through some related pathways. Experimental results also confirmed that those core ingredients could significantly increase HUVEC viability and attenuate the expression of ICAM-1, which supported the effectiveness of MSW in treating gouty diseases. Moreover, heat-clearing and dampness-eliminating herbs in MSW have similar physicochemical properties, which stimulate all the inflammatory and uric acid-lowing targets respectively, while the core drug and basic prescription in MSW stimulate the major and almost all the core targets, respectively. Our work successfully predicts the active ingredients in MSW and explains the cooperation between these ingredients and corresponding targets through related pathways for gouty diseases, and provides basis for an alternative approach to investigate the rationality of herb combinations of MSW on the network pharmacology level, which might be beneficial to drug development and applications. Copyright © 2015. Published by Elsevier Ireland Ltd.

Urate oxidase is imported into peroxisomes recognizing the C-terminal SKL motif of proteins.

PubMed

Miura, S; Oda, T; Funai, T; Ito, M; Okada, Y; Ichiyama, A

1994-07-01

Rat liver urate oxidase synthesized from cDNA through coupled transcription and translation was incubated at 26 degrees C for 60 min with purified peroxisomes from rat liver. Urate oxidase was efficiently imported into the peroxisomes, as determined by resistance to externally added proteinase K. The amount of imported urate oxidase increased with time and the import was temperature dependent. A synthetic peptide composed of the C-terminal 10 amino acid residues of acyl-CoA oxidase (the C-terminal tripeptide is Ser-Lys-Leu) inhibited the import of urate oxidase, whereas other peptides, in which the C-terminal Ser-Lys-Leu (SKL) sequence was deleted or mutated, were not effective. Two mutant urate oxidase proteins in which the C-terminal Ser-Arg-Leu (SRL) sequence was deleted or mutated to Ser-Glu-Leu (SEL) were not imported into peroxisomes. With substitution of a lysine residue for arginine in the SRL tripeptide at the C-terminus the import activity was retained. These results show that urate oxidase is important into peroxisomes via a common pathway with acyl-CoA oxidase, and that the C-terminal SRL sequence functions as a peroxisomal-targeting signal.

SLC2A9 is a high-capacity urate transporter in humans.

PubMed

Caulfield, Mark J; Munroe, Patricia B; O'Neill, Deb; Witkowska, Kate; Charchar, Fadi J; Doblado, Manuel; Evans, Sarah; Eyheramendy, Susana; Onipinla, Abiodun; Howard, Philip; Shaw-Hawkins, Sue; Dobson, Richard J; Wallace, Chris; Newhouse, Stephen J; Brown, Morris; Connell, John M; Dominiczak, Anna; Farrall, Martin; Lathrop, G Mark; Samani, Nilesh J; Kumari, Meena; Marmot, Michael; Brunner, Eric; Chambers, John; Elliott, Paul; Kooner, Jaspal; Laan, Maris; Org, Elin; Veldre, Gudrun; Viigimaa, Margus; Cappuccio, Francesco P; Ji, Chen; Iacone, Roberto; Strazzullo, Pasquale; Moley, Kelle H; Cheeseman, Chris

2008-10-07

Serum uric acid levels in humans are influenced by diet, cellular breakdown, and renal elimination, and correlate with blood pressure, metabolic syndrome, diabetes, gout, and cardiovascular disease. Recent genome-wide association scans have found common genetic variants of SLC2A9 to be associated with increased serum urate level and gout. The SLC2A9 gene encodes a facilitative glucose transporter, and it has two splice variants that are highly expressed in the proximal nephron, a key site for urate handling in the kidney. We investigated whether SLC2A9 is a functional urate transporter that contributes to the longstanding association between urate and blood pressure in man. We expressed both SLC2A9 splice variants in Xenopus laevis oocytes and found both isoforms mediate rapid urate fluxes at concentration ranges similar to physiological serum levels (200-500 microM). Because SLC2A9 is a known facilitative glucose transporter, we also tested whether glucose or fructose influenced urate transport. We found that urate is transported by SLC2A9 at rates 45- to 60-fold faster than glucose, and demonstrated that SLC2A9-mediated urate transport is facilitated by glucose and, to a lesser extent, fructose. In addition, transport is inhibited by the uricosuric benzbromarone in a dose-dependent manner (Ki = 27 microM). Furthermore, we found urate uptake was at least 2-fold greater in human embryonic kidney (HEK) cells overexpressing SLC2A9 splice variants than nontransfected kidney cells. To confirm that our findings were due to SLC2A9, and not another urate transporter, we showed that urate transport was diminished by SLC2A9-targeted siRNA in a second mammalian cell line. In a cohort of men we showed that genetic variants of SLC2A9 are associated with reduced urinary urate clearance, which fits with common variation at SLC2A9 leading to increased serum urate. We found no evidence of association with hypertension (odds ratio 0.98, 95% confidence interval [CI] 0.9 to 1.05, p > 0.33) by meta-analysis of an SLC2A9 variant in six case-control studies including 11,897 participants. In a separate meta-analysis of four population studies including 11,629 participants we found no association of SLC2A9 with systolic (effect size -0.12 mm Hg, 95% CI -0.68 to 0.43, p = 0.664) or diastolic blood pressure (effect size -0.03 mm Hg, 95% CI -0.39 to 0.31, p = 0.82). This study provides evidence that SLC2A9 splice variants act as high-capacity urate transporters and is one of the first functional characterisations of findings from genome-wide association scans. We did not find an association of the SLC2A9 gene with blood pressure in this study. Our findings suggest potential pathogenic mechanisms that could offer a new drug target for gout.

SLC2A9 Is a High-Capacity Urate Transporter in Humans

PubMed Central

O'Neill, Deb; Witkowska, Kate; Charchar, Fadi J; Doblado, Manuel; Evans, Sarah; Eyheramendy, Susana; Onipinla, Abiodun; Howard, Philip; Shaw-Hawkins, Sue; Dobson, Richard J; Wallace, Chris; Newhouse, Stephen J; Brown, Morris; Connell, John M; Dominiczak, Anna; Farrall, Martin; Lathrop, G. Mark; Samani, Nilesh J; Kumari, Meena; Marmot, Michael; Brunner, Eric; Chambers, John; Elliott, Paul; Kooner, Jaspal; Laan, Maris; Org, Elin; Veldre, Gudrun; Viigimaa, Margus; Cappuccio, Francesco P; Ji, Chen; Iacone, Roberto; Strazzullo, Pasquale; Moley, Kelle H; Cheeseman, Chris

2008-01-01

Background Serum uric acid levels in humans are influenced by diet, cellular breakdown, and renal elimination, and correlate with blood pressure, metabolic syndrome, diabetes, gout, and cardiovascular disease. Recent genome-wide association scans have found common genetic variants of SLC2A9 to be associated with increased serum urate level and gout. The SLC2A9 gene encodes a facilitative glucose transporter, and it has two splice variants that are highly expressed in the proximal nephron, a key site for urate handling in the kidney. We investigated whether SLC2A9 is a functional urate transporter that contributes to the longstanding association between urate and blood pressure in man. Methods and Findings We expressed both SLC2A9 splice variants in Xenopus laevis oocytes and found both isoforms mediate rapid urate fluxes at concentration ranges similar to physiological serum levels (200–500 μM). Because SLC2A9 is a known facilitative glucose transporter, we also tested whether glucose or fructose influenced urate transport. We found that urate is transported by SLC2A9 at rates 45- to 60-fold faster than glucose, and demonstrated that SLC2A9-mediated urate transport is facilitated by glucose and, to a lesser extent, fructose. In addition, transport is inhibited by the uricosuric benzbromarone in a dose-dependent manner (K i = 27 μM). Furthermore, we found urate uptake was at least 2-fold greater in human embryonic kidney (HEK) cells overexpressing SLC2A9 splice variants than nontransfected kidney cells. To confirm that our findings were due to SLC2A9, and not another urate transporter, we showed that urate transport was diminished by SLC2A9-targeted siRNA in a second mammalian cell line. In a cohort of men we showed that genetic variants of SLC2A9 are associated with reduced urinary urate clearance, which fits with common variation at SLC2A9 leading to increased serum urate. We found no evidence of association with hypertension (odds ratio 0.98, 95% confidence interval [CI] 0.9 to 1.05, p > 0.33) by meta-analysis of an SLC2A9 variant in six case–control studies including 11,897 participants. In a separate meta-analysis of four population studies including 11,629 participants we found no association of SLC2A9 with systolic (effect size −0.12 mm Hg, 95% CI −0.68 to 0.43, p = 0.664) or diastolic blood pressure (effect size −0.03 mm Hg, 95% CI −0.39 to 0.31, p = 0.82). Conclusions This study provides evidence that SLC2A9 splice variants act as high-capacity urate transporters and is one of the first functional characterisations of findings from genome-wide association scans. We did not find an association of the SLC2A9 gene with blood pressure in this study. Our findings suggest potential pathogenic mechanisms that could offer a new drug target for gout. PMID:18842065

Gout therapeutics: new drugs for an old disease.

PubMed

Burns, Christopher M; Wortmann, Robert L

2011-01-08

The approval of febuxostat, a non-purine-analogue inhibitor of xanthine oxidase, by the European Medicines Agency and the US Food and Drug Administration heralds a new era in the treatment of gout. The use of modified uricases to rapidly reduce serum urate concentrations in patients with otherwise untreatable gout is progressing. Additionally, advances in our understanding of the transport of uric acid in the renal proximal tubule and the inflammatory response to monosodium urate crystals are translating into potential new treatments. In this Review, we focus on the clinical trials of febuxostat. We also review results from studies of pegloticase, a pegylated uricase in development, and we summarise data for several other pipeline drugs for gout, such as the selective uricosuric drug RDEA594 and various interleukin-1 inhibitors. Finally, we issue a word of caution about the proper use of the new drugs and the already available drugs for gout. At a time of important advances, we need to recommit ourselves to a rational approach to the treatment of gout. Copyright © 2011 Elsevier Ltd. All rights reserved.

Racial and Gender Disparities in Patients with Gout

PubMed Central

Singh, Jasvinder A.

2012-01-01

Gout affects 8.3 million Americans according to NHANES 2007–2008, roughly 3.9% of the U.S. population. Gout has significant impact on physical function, productivity, health-related quality of life (HRQOL) and health care costs. Uncontrolled gout is also associated with significant utilization of emergent care services. Women are less likely to have gout than men, but in the postmenopausal years the gender difference in disease incidence decreases. Compared to Whites, racial/ethnic minorities, especially blacks, have higher prevalence of gout. On the other hand, blacks are less likely to receive quality gout care, leading to a disproportionate morbidity. Women are less likely than men to receive allopurinol, less likely to get joint aspirations for crystal analyses for establishing diagnosis, but those on urate-lowering therapy are as/more likely as men to get serum urate check within 6-months of initiation. While a few studies provide the knowledge related to gender and race/ethnicity disparities in gout, several knowledge gaps exist in gout epidemiology and outcomes differences by gender and race/ethnicity. These should be explored in future studies. PMID:23315156

Genome-wide association analysis identifies three new risk loci for gout arthritis in Han Chinese

PubMed Central

Li, Changgui; Li, Zhiqiang; Liu, Shiguo; Wang, Can; Han, Lin; Cui, Lingling; Zhou, Jingguo; Zou, Hejian; Liu, Zhen; Chen, Jianhua; Cheng, Xiaoyu; Zhou, Zhaowei; Ding, Chengcheng; Wang, Meng; Chen, Tong; Cui, Ying; He, Hongmei; Zhang, Keke; Yin, Congcong; Wang, Yunlong; Xing, Shichao; Li, Baojie; Ji, Jue; Jia, Zhaotong; Ma, Lidan; Niu, Jiapeng; Xin, Ying; Liu, Tian; Chu, Nan; Yu, Qing; Ren, Wei; Wang, Xuefeng; Zhang, Aiqing; Sun, Yuping; Wang, Haili; Lu, Jie; Li, Yuanyuan; Qing, Yufeng; Chen, Gang; Wang, Yangang; Zhou, Li; Niu, Haitao; Liang, Jun; Dong, Qian; Li, Xinde; Mi, Qing-Sheng; Shi, Yongyong

2015-01-01

Gout is one of the most common types of inflammatory arthritis, caused by the deposition of monosodium urate crystals in and around the joints. Previous genome-wide association studies (GWASs) have identified many genetic loci associated with raised serum urate concentrations. However, hyperuricemia alone is not sufficient for the development of gout arthritis. Here we conduct a multistage GWAS in Han Chinese using 4,275 male gout patients and 6,272 normal male controls (1,255 cases and 1,848 controls were genome-wide genotyped), with an additional 1,644 hyperuricemic controls. We discover three new risk loci, 17q23.2 (rs11653176, P=1.36 × 10−13, BCAS3), 9p24.2 (rs12236871, P=1.48 × 10−10, RFX3) and 11p15.5 (rs179785, P=1.28 × 10−8, KCNQ1), which contain inflammatory candidate genes. Our results suggest that these loci are most likely related to the progression from hyperuricemia to inflammatory gout, which will provide new insights into the pathogenesis of gout arthritis. PMID:25967671

Genome-wide association analysis identifies three new risk loci for gout arthritis in Han Chinese.

PubMed

Li, Changgui; Li, Zhiqiang; Liu, Shiguo; Wang, Can; Han, Lin; Cui, Lingling; Zhou, Jingguo; Zou, Hejian; Liu, Zhen; Chen, Jianhua; Cheng, Xiaoyu; Zhou, Zhaowei; Ding, Chengcheng; Wang, Meng; Chen, Tong; Cui, Ying; He, Hongmei; Zhang, Keke; Yin, Congcong; Wang, Yunlong; Xing, Shichao; Li, Baojie; Ji, Jue; Jia, Zhaotong; Ma, Lidan; Niu, Jiapeng; Xin, Ying; Liu, Tian; Chu, Nan; Yu, Qing; Ren, Wei; Wang, Xuefeng; Zhang, Aiqing; Sun, Yuping; Wang, Haili; Lu, Jie; Li, Yuanyuan; Qing, Yufeng; Chen, Gang; Wang, Yangang; Zhou, Li; Niu, Haitao; Liang, Jun; Dong, Qian; Li, Xinde; Mi, Qing-Sheng; Shi, Yongyong

2015-05-13

Gout is one of the most common types of inflammatory arthritis, caused by the deposition of monosodium urate crystals in and around the joints. Previous genome-wide association studies (GWASs) have identified many genetic loci associated with raised serum urate concentrations. However, hyperuricemia alone is not sufficient for the development of gout arthritis. Here we conduct a multistage GWAS in Han Chinese using 4,275 male gout patients and 6,272 normal male controls (1,255 cases and 1,848 controls were genome-wide genotyped), with an additional 1,644 hyperuricemic controls. We discover three new risk loci, 17q23.2 (rs11653176, P=1.36 × 10(-13), BCAS3), 9p24.2 (rs12236871, P=1.48 × 10(-10), RFX3) and 11p15.5 (rs179785, P=1.28 × 10(-8), KCNQ1), which contain inflammatory candidate genes. Our results suggest that these loci are most likely related to the progression from hyperuricemia to inflammatory gout, which will provide new insights into the pathogenesis of gout arthritis.

Uric acid is released in the brain during seizure activity and increases severity of seizures in a mouse model for acute limbic seizures.

PubMed

Thyrion, Lisa; Raedt, Robrecht; Portelli, Jeanelle; Van Loo, Pieter; Wadman, Wytse J; Glorieux, Griet; Lambrecht, Bart N; Janssens, Sophie; Vonck, Kristl; Boon, Paul

2016-03-01

Recent evidence points at an important role of endogenous cell-damage induced pro-inflammatory molecules in the generation of epileptic seizures. Uric acid, under the form of monosodium urate crystals, has shown to have pro-inflammatory properties in the body, but less is known about its role in seizure generation. This study aimed to unravel the contribution of uric acid to seizure generation in a mouse model for acute limbic seizures. We measured extracellular levels of uric acid in the brain and modulated them using complementary pharmacological and genetic tools. Local extracellular uric acid levels increased three to four times during acute limbic seizures and peaked between 50 and 100 min after kainic acid infusion. Manipulating uric acid levels through administration of allopurinol or knock-out of urate oxidase significantly altered the number of generalized seizures, decreasing and increasing them by a twofold respectively. Taken together, our results consistently show that uric acid is released during limbic seizures and suggest that uric acid facilitates seizure generalization. Copyright © 2016 Elsevier Inc. All rights reserved.

Cooperative Extension as a Framework for Health Extension: The Michigan State University Model

PubMed Central

Dwyer, Jeffrey W.; Contreras, Dawn; Tiret, Holly; Newkirk, Cathy; Carter, Erin; Cronk, Linda

2017-01-01

Problem The Affordable Care Act charged the Agency for Healthcare Research and Quality to create the Primary Care Extension Program, but did not fund this effort. The idea to work through health extension agents to support health care delivery systems was based on the nationally known Cooperative Extension System (CES). Instead of creating new infrastructure in health care, the CES is an ideal vehicle for increasing health-related research and primary care delivery. Approach The CES, a long-standing component of the land-grant university system, features a sustained infrastructure for providing education to communities. The Michigan State University (MSU) Model of Health Extension offers another means of developing a National Primary Care Extension Program that is replicable in part because of the presence of the CES throughout the United States. A partnership between the MSU College of Human Medicine and MSU Extension formed in 2014, emphasizing the promotion and support of human health research. The MSU Model of Health Extension includes the following strategies: building partnerships, preparing MSU Extension educators for participation in research, increasing primary care patient referrals and enrollment in health programs, and exploring innovative funding. Outcomes Since the formation of the MSU Model of Health Extension, researchers and extension professionals have made 200+ connections, and grants have afforded savings in salary costs. Next Steps The MSU College of Human Medicine and MSU Extension partnership can serve as a model to promote health partnerships nationwide between CES services within land-grant universities and academic health centers or community-based medical schools. PMID:28353501

Management of Gout in a Hospital Setting: A Lost Opportunity.

PubMed

Wright, Sarah; Chapman, Peter T; Frampton, Christopher; O'Donnell, John L; Raja, Rafi; Stamp, Lisa K

2017-10-01

Management of gout is frequently suboptimal. The aim of this study was to determine the proportion of patients presenting to Christchurch Hospital for a gout flare and to determine whether management for both acute flares and urate lowering was in accordance with international recommendations. A retrospective audit was undertaken of all admissions to Christchurch Hospital from June 1, 2013, to May 31, 2014, in which gout was coded as a primary or secondary discharge diagnosis. Information including demographics, comorbidities, concomitant medications, treatment of acute gout, and urate lowering was collected. A total of 235 acute admissions for gout in 216 individuals were identified. Eleven individuals had 2 admissions and 4 individuals had 3 admissions. In 95/235 admissions (40.4%), gout was the primary diagnosis. Gout accounted for 95/77,321 (0.12%) of acute admissions. The treatment of acute gout was prednisone monotherapy in 170/235 (72.3%) of admissions. Serum urate was measured at some point during 123/235 (52.3%) of admissions, with only 19/123 (15.4%) at target urate level (< 0.36 mmol/l). At 60 of the 235 admissions, urate-lowering therapy was already being prescribed. Nine out of 175 patients (5.1%) not treated with urate-lowering therapy at admission commenced allopurinol and 32/174 (18.4%) had commencement of urate-lowering therapy recommended in the discharge plan. Rates of admission for gout are similar to that observed in other studies. Failure to initiate, change, or recommend alterations in urate-lowering therapy to achieve target urate in people with gout admitted to hospital represents a significant lost opportunity to improve longterm gout management.

Effects of multiple genetic loci on the pathogenesis from serum urate to gout

PubMed Central

Dong, Zheng; Zhou, Jingru; Jiang, Shuai; Li, Yuan; Zhao, Dongbao; Yang, Chengde; Ma, Yanyun; Wang, Yi; He, Hongjun; Ji, Hengdong; Yang, Yajun; Wang, Xiaofeng; Xu, Xia; Pang, Yafei; Zou, Hejian; Jin, Li; Wang, Jiucun

2017-01-01

Gout is a common arthritis resulting from increased serum urate, and many loci have been identified that are associated with serum urate and gout. However, their influence on the progression from elevated serum urate levels to gout is unclear. This study aims to explore systematically the effects of genetic variants on the pathogenesis in approximately 5,000 Chinese individuals. Six genes (PDZK1, GCKR, TRIM46, HNF4G, SLC17A1, LRRC16A) were determined to be associated with serum urate (PFDR < 0.05) in the Chinese population for the first time. ABCG2 and a novel gene, SLC17A4, contributed to the development of gout from hyperuricemia (OR = 1.56, PFDR = 3.68E-09; OR = 1.27, PFDR = 0.013, respectively). Also, HNF4G is a novel gene associated with susceptibility to gout (OR = 1.28, PFDR = 1.08E-03). In addition, A1CF and TRIM46 were identified as associated with gout in the Chinese population for the first time (PFDR < 0.05). The present study systematically determined genetic effects on the progression from elevated serum urate to gout and suggests that urate-associated genes functioning as urate transporters may play a specific role in the pathogenesis of gout. Furthermore, two novel gout-associated genes (HNF4G and SLC17A4) were identified. PMID:28252667

Effects of multiple genetic loci on the pathogenesis from serum urate to gout.

PubMed

Dong, Zheng; Zhou, Jingru; Jiang, Shuai; Li, Yuan; Zhao, Dongbao; Yang, Chengde; Ma, Yanyun; Wang, Yi; He, Hongjun; Ji, Hengdong; Yang, Yajun; Wang, Xiaofeng; Xu, Xia; Pang, Yafei; Zou, Hejian; Jin, Li; Wang, Jiucun

2017-03-02

Gout is a common arthritis resulting from increased serum urate, and many loci have been identified that are associated with serum urate and gout. However, their influence on the progression from elevated serum urate levels to gout is unclear. This study aims to explore systematically the effects of genetic variants on the pathogenesis in approximately 5,000 Chinese individuals. Six genes (PDZK1, GCKR, TRIM46, HNF4G, SLC17A1, LRRC16A) were determined to be associated with serum urate (P FDR  < 0.05) in the Chinese population for the first time. ABCG2 and a novel gene, SLC17A4, contributed to the development of gout from hyperuricemia (OR = 1.56, P FDR  = 3.68E-09; OR = 1.27, P FDR  = 0.013, respectively). Also, HNF4G is a novel gene associated with susceptibility to gout (OR = 1.28, P FDR  = 1.08E-03). In addition, A1CF and TRIM46 were identified as associated with gout in the Chinese population for the first time (P FDR  < 0.05). The present study systematically determined genetic effects on the progression from elevated serum urate to gout and suggests that urate-associated genes functioning as urate transporters may play a specific role in the pathogenesis of gout. Furthermore, two novel gout-associated genes (HNF4G and SLC17A4) were identified.

Flavonoids and urate antioxidant interplay in plasma oxidative stress.

PubMed

Filipe, P; Lança, V; Silva, J N; Morlière, P; Santus, R; Fernandes, A

2001-05-01

Flavonoids are naturally occurring plant compounds with antioxidant properties. Their consumption has been associated with the protective effects of certain diets against some of the complications of atherosclerosis. Low-density lipoprotein (LDL) oxidative modification is currently thought to be a significant event in the atherogenic process. Most of the experiments concerning the inhibition of LDL oxidation used isolated LDL. We used diluted human whole plasma to study the influence of flavonoids on lipid peroxidation (LPO) promoted by copper, and their interaction with uric acid, one of the most important plasma antioxidants. Lipid peroxidation was evaluated by the formation of thiobarbituric acid reactive substances (TBARS) and of free malondialdehyde (MDA). The comparative capability of the assayed flavonoids on copper (II) reduction was tested using the neocuproine colorimetric test. In our assay system, urate disappears and free MDA and TBARS formation increase during the incubation of plasma with copper. Most of the tested flavonoids inhibited copper-induced LPO. The inhibition of LPO by flavonoids correlated positively with their capability to reduce copper (II). The urate consumption during the incubation of plasma with copper was inhibited by myricetin, quercetin and kaempferol. The inhibition of urate degradation by flavonoids correlated positively with the inhibition of LPO. Urate inhibited the copper-induced LPO in a concentration-dependent mode. Luteolin, rutin, catechin and quercetin had an antioxidant synergy with urate. Our results show that some flavonoids could protect endogenous urate from oxidative degradation, and demonstrate an antioxidant synergy between urate and some of the flavonoids.

A Novel Multi-Epitope Vaccine Based on Urate Transporter 1 Alleviates Streptozotocin-Induced Diabetes by Producing Anti-URAT1 Antibody and an Immunomodulatory Effect in C57BL/6J Mice.

PubMed

Ma, Yanjie; Cao, Huimin; Li, Zhixin; Fang, Jinzhi; Wei, Xiaomin; Cheng, Peng; Jiao, Rui; Liu, Xiaoran; Li, Ya; Xing, Yun; Tang, Jiali; Jin, Liang; Li, Taiming

2017-10-16

Hyperuricemia (HUA) is related to diabetes. Uric acid-induced inflammation and oxidative stress are risk factors for diabetes and its complications. Human urate transporter 1 (URAT1) regulates the renal tubular reabsorption of uric acid. IA-2(5)-P2-1, a potent immunogenic carrier designed by our laboratory, can induce high-titer specific antibodies when it carries a B cell epitope, such as B cell epitopes of DPP4 (Dipeptidyl peptidase-4), xanthine oxidase. In this report, we describe a novel multi-epitope vaccine composing a peptide of URAT1, an anti-diabetic B epitope of insulinoma antigen-2(IA-2) and a Th2 epitope (P2:IPALDSLTPANED) of P277 peptide in human heat shock protein 60 (HSP60). Immunization with the multi-epitope vaccine in streptozotocin-induced diabetes C57BL/6J mice successfully induced specific anti-URAT1 antibody, which inhibited URAT1 action and uric acid reabsorption, and increased pancreatic insulin level with a lower insulitis incidence. Vaccination with U-IA-2(5)-P2-1 (UIP-1) significantly reduced blood glucose and uric acid level, increased Th2 cytokines interleukin (IL)-10 and IL-4, and regulated immune reactions through a balanced Th1/Th2 ratio. These results demonstrate that the URAT1-based multi-epitope peptide vaccine may be a suitable therapeutic approach for diabetes and its complications.

THE ASSOCIATION BETWEEN SERUM FERRITIN AND URIC ACID IN HUMANS

EPA Science Inventory

OBJECTIVE: Urate forms a coordination complex with Fe(3+) which does not support electron transport. The only enzymatic source of urate is xanthine oxidoreductase. If a major purpose of xanthine oxidoreductase is the production of urate to function as an iron chelator and antioxi...

Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis.

PubMed

White, Jon; Sofat, Reecha; Hemani, Gibran; Shah, Tina; Engmann, Jorgen; Dale, Caroline; Shah, Sonia; Kruger, Felix A; Giambartolomei, Claudia; Swerdlow, Daniel I; Palmer, Tom; McLachlan, Stela; Langenberg, Claudia; Zabaneh, Delilah; Lovering, Ruth; Cavadino, Alana; Jefferis, Barbara; Finan, Chris; Wong, Andrew; Amuzu, Antoinette; Ong, Ken; Gaunt, Tom R; Warren, Helen; Davies, Teri-Louise; Drenos, Fotios; Cooper, Jackie; Ebrahim, Shah; Lawlor, Debbie A; Talmud, Philippa J; Humphries, Steve E; Power, Christine; Hypponen, Elina; Richards, Marcus; Hardy, Rebecca; Kuh, Diana; Wareham, Nicholas; Ben-Shlomo, Yoav; Day, Ian N; Whincup, Peter; Morris, Richard; Strachan, Mark W J; Price, Jacqueline; Kumari, Meena; Kivimaki, Mika; Plagnol, Vincent; Whittaker, John C; Smith, George Davey; Dudbridge, Frank; Casas, Juan P; Holmes, Michael V; Hingorani, Aroon D

2016-04-01

Increased circulating plasma urate concentration is associated with an increased risk of coronary heart disease, but the extent of any causative effect of urate on risk of coronary heart disease is still unclear. In this study, we aimed to clarify any causal role of urate on coronary heart disease risk using Mendelian randomisation analysis. We first did a fixed-effects meta-analysis of the observational association of plasma urate and risk of coronary heart disease. We then used a conventional Mendelian randomisation approach to investigate the causal relevance using a genetic instrument based on 31 urate-associated single nucleotide polymorphisms (SNPs). To account for potential pleiotropic associations of certain SNPs with risk factors other than urate, we additionally did both a multivariable Mendelian randomisation analysis, in which the genetic associations of SNPs with systolic and diastolic blood pressure, HDL cholesterol, and triglycerides were included as covariates, and an Egger Mendelian randomisation (MR-Egger) analysis to estimate a causal effect accounting for unmeasured pleiotropy. In the meta-analysis of 17 prospective observational studies (166 486 individuals; 9784 coronary heart disease events) a 1 SD higher urate concentration was associated with an odds ratio (OR) for coronary heart disease of 1·07 (95% CI 1·04-1·10). The corresponding OR estimates from the conventional, multivariable adjusted, and Egger Mendelian randomisation analysis (58 studies; 198 598 individuals; 65 877 events) were 1·18 (95% CI 1·08-1·29), 1·10 (1·00-1·22), and 1·05 (0·92-1·20), respectively, per 1 SD increment in plasma urate. Conventional and multivariate Mendelian randomisation analysis implicates a causal role for urate in the development of coronary heart disease, but these estimates might be inflated by hidden pleiotropy. Egger Mendelian randomisation analysis, which accounts for pleiotropy but has less statistical power, suggests there might be no causal effect. These results might help investigators to determine the priority of trials of urate lowering for the prevention of coronary heart disease compared with other potential interventions. UK National Institute for Health Research, British Heart Foundation, and UK Medical Research Council. Copyright © 2016 White et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Plasma urate concentration and risk of coronary heart disease: a Mendelian randomisation analysis

PubMed Central

White, Jon; Sofat, Reecha; Hemani, Gibran; Shah, Tina; Engmann, Jorgen; Dale, Caroline; Shah, Sonia; Kruger, Felix A; Giambartolomei, Claudia; Swerdlow, Daniel I; Palmer, Tom; McLachlan, Stela; Langenberg, Claudia; Zabaneh, Delilah; Lovering, Ruth; Cavadino, Alana; Jefferis, Barbara; Finan, Chris; Wong, Andrew; Amuzu, Antoinette; Ong, Ken; Gaunt, Tom R; Warren, Helen; Davies, Teri-Louise; Drenos, Fotios; Cooper, Jackie; Ebrahim, Shah; Lawlor, Debbie A; Talmud, Philippa J; Humphries, Steve E; Power, Christine; Hypponen, Elina; Richards, Marcus; Hardy, Rebecca; Kuh, Diana; Wareham, Nicholas; Ben-Shlomo, Yoav; Day, Ian N; Whincup, Peter; Morris, Richard; Strachan, Mark W J; Price, Jacqueline; Kumari, Meena; Kivimaki, Mika; Plagnol, Vincent; Whittaker, John C; Smith, George Davey; Dudbridge, Frank; Casas, Juan P; Holmes, Michael V; Hingorani, Aroon D

2016-01-01

Summary Background Increased circulating plasma urate concentration is associated with an increased risk of coronary heart disease, but the extent of any causative effect of urate on risk of coronary heart disease is still unclear. In this study, we aimed to clarify any causal role of urate on coronary heart disease risk using Mendelian randomisation analysis. Methods We first did a fixed-effects meta-analysis of the observational association of plasma urate and risk of coronary heart disease. We then used a conventional Mendelian randomisation approach to investigate the causal relevance using a genetic instrument based on 31 urate-associated single nucleotide polymorphisms (SNPs). To account for potential pleiotropic associations of certain SNPs with risk factors other than urate, we additionally did both a multivariable Mendelian randomisation analysis, in which the genetic associations of SNPs with systolic and diastolic blood pressure, HDL cholesterol, and triglycerides were included as covariates, and an Egger Mendelian randomisation (MR-Egger) analysis to estimate a causal effect accounting for unmeasured pleiotropy. Findings In the meta-analysis of 17 prospective observational studies (166 486 individuals; 9784 coronary heart disease events) a 1 SD higher urate concentration was associated with an odds ratio (OR) for coronary heart disease of 1·07 (95% CI 1·04–1·10). The corresponding OR estimates from the conventional, multivariable adjusted, and Egger Mendelian randomisation analysis (58 studies; 198 598 individuals; 65 877 events) were 1·18 (95% CI 1·08–1·29), 1·10 (1·00–1·22), and 1·05 (0·92–1·20), respectively, per 1 SD increment in plasma urate. Interpretation Conventional and multivariate Mendelian randomisation analysis implicates a causal role for urate in the development of coronary heart disease, but these estimates might be inflated by hidden pleiotropy. Egger Mendelian randomisation analysis, which accounts for pleiotropy but has less statistical power, suggests there might be no causal effect. These results might help investigators to determine the priority of trials of urate lowering for the prevention of coronary heart disease compared with other potential interventions. Funding UK National Institute for Health Research, British Heart Foundation, and UK Medical Research Council. PMID:26781229

Are Michigan State University medical school (MSU-CHM) alumni more likely to practice in the region of their graduate medical education primary care program compared to non-MSU-CHM alumni?

PubMed

Switzer, Richard; VandeZande, Luke; Davis, Alan T; Koehler, Tracy J

2018-05-24

Over the past 10 years, three new MD schools have been created in the state of Michigan, while the Michigan State University College of Human Medicine (MSU-CHM) has increased their class size to 850 students. The aim of this study was to determine if MSU-CHM alumni who graduate from an MSU-affiliated primary care residency from a single graduate medical education (GME) training program in Michigan are more likely to go on to practice in close proximity to the location of their training program immediately after graduation compared to non MSU-CHM alumni. Changes over time in the proportion of primary care graduates who received fellowship training immediately following residency were also compared between these groups. A review of historical data was performed for all 2000-2016 primary care (Family Medicine, FM; Internal Medicine, IM; Internal Medicine-Pediatrics, IMP; Pediatrics, Peds) program graduates sponsored by Grand Rapids Medical Education Partners (GRMEP). Study variables included primary care program, gender, age at graduation, fellowship training, practice location immediately after graduation and undergraduate medical education location. Summary statistics were calculated for the data. Comparisons were made using the chi-square test or Fisher's Exact test when appropriate. Significance was assessed at p < 0.05. There were 478 primary care program graduates who went into practice immediately following graduation, 102 of whom also graduated from MSU-CHM. Just over half of the graduates were female and the average age at graduation was 32 years. There were 152 FM, 150 IM, 50 IMP and 126 Peds graduates. Those that graduated from both MSU-CHM and GRMEP were more likely to practice in Michigan immediately after residency training (79.4% vs 52.0%; p < 0.001), as well as within 100 miles of GRMEP (71.6% vs 46.4%; p < 0.001). There were 8% of MSU-CHM primary care graduates who went on to fellowship training from 2000 to 2009, increasing to 34% from 2010 to 2016 (p < 0.001). Medical school graduates of MSU-CHM who receive GME training in primary care are more likely to practice medicine within close proximity to their training site than non MSU-CHM graduates. However, plans for fellowship after training may add one caveat to this finding.

Power generation and solar panels for an MSU CubeSat

NASA Astrophysics Data System (ADS)

Sassi, Soundouss

This thesis is a power generation study of a proposed CubeSat at Mississippi State University (MSU). CubeSats are miniaturized satellites of 10 x 10 x 10 cm in dimension. Their power source once in orbit is the sun during daylight and the batteries during eclipse. MSU CubeSat is equipped with solar panels. This effort will discuss two types of cells: Gallium Arsenide and Silicon; and which one will suit MSU CubeSat best. Once the cell type is chosen, another decision regarding the electrical power subsystem will be made. Solar array design can only be done once the choice of the electrical power subsystem and the solar cells is made. Then the power calculation for different mission durations will start along with the sizing of the solar arrays. In the last part the batteries are introduced and discussed in order to choose one type of batteries for MSU CubeSat.

Assessing applicants to the NASA flight program for their renal stone-forming potential

NASA Technical Reports Server (NTRS)

Pak, Charles Y. C.; Hill, Kathy; Cintron, Nitza M.; Huntoon, Carolyn

1989-01-01

Because spaceflight can provoke the formation of kidney stones, 24-hour urine samples for 104 male applicants were analyzed for stone-forming risk factors prior to their selection into the NASA astronaut-mission specialist corps. A high level of supersaturation (with either calcium oxalate, brushite, or monosodium urate) was noted in these applicants which predisposes them to the crystallization of stone-forming calcium salts. It is suggested that most of the abnormal stone risk factors found were environmental, rather than metabolic, in origin.

The kidney in hyperuricemia and gout.

PubMed

Mount, David B

2013-03-01

Gout is a painful inflammatory arthritis associated with hyperuricemia, with a prevalence of almost 10 million in the USA. Reduced renal excretion of urate is the underlying hyperuricemic mechanism in the vast majority of gout patients; most of the genes that affect serum urate level (SUA) encode urate transporters or associated regulatory proteins. Acquired influences can also modulate SUA and renal urate excretion, sometimes precipitating acute gout. Coincidentally, the prevalence of renal comorbidities in gout - hypertension, chronic kidney disease (CKD), and nephrolithiasis - is very high. Recent advances in genetics and molecular physiology have greatly enhanced the understanding of renal reabsorption and secretion of filtered urate. Moreover, baseline SUA appears to be set by the net balance of absorption and secretion across epithelial cells in the kidney and intestine. There have also been substantial advances in the management of gout in patients with CKD. The stage is set for an increasingly molecular understanding of baseline and regulated urate transport by the kidney and intestine. The increasing prevalence of gout with CKD will be balanced by an expanding spectrum of therapeutic options for this important disease.

Levels of cytokines and microRNAs in individuals with asymptomatic hyperuricemia and ultrasonographic findings of gout: a bench-to-bedside approach.

PubMed

Estevez-Garcia, Irving O; Gallegos-Nava, Selma; Vera-Pérez, Erika; Silveira, Luis H; Ventura-Ríos, Lucio; Vancini, Gonzalo; Hernández-Díaz, Cristina; Sánchez-Muñoz, Fausto; Ballinas-Verdugo, Martha A; Gutierrez, Marwin; Pineda, Carlos; Rodriguez-Henriquez, Pedro; Castillo-Martínez, Diana; Amezcua-Guerra, Luis M

2018-02-18

To assess potential associations among serum cytokines and microRNA (miR) levels with ultrasound (US) findings suggestive of urate deposits in chronic asymptomatic hyperuricemia and gout. All participants underwent musculoskeletal US and measurements of serum IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IFN-γ, TNF, MCP-1, and ENA-78, as well as miR-146a, miR-155, and miR-223 levels. Thirty individuals with asymptomatic hyperuricemia, 31 normouricemic controls, and 30 gouty patients were included. The frequency of synovitis and double contour sign using US was similar between asymptomatic hyperuricemia (67% and 27%, respectively) and gouty participants (77% and 27%), and each had a higher frequency than controls (45% and 0%). Serum IL-6 and IL-8 levels were similar between patients with asymptomatic hyperuricemia (69.7±73.4 and 18.5±25.6 pg/ml, respectively) and gout (75.8±47.6 and 24.4±31.7 pg/ml), and higher than controls (28.2±17.6 and 7.4±6.0 pg/ml). A similar distribution was observed for miR-155 levels (0.22±0.18, 0.20±0.14, and 0.08±0.04, respectively). Associations between morphostructural abnormalities suggestive of urate deposits (regardless of clinical diagnosis) and serum markers were assessed. Subjects with urate deposits had higher IL-6 (257.2 versus 47.0 pg/mL; P=0.005), IL-8 (73.2 versus 12.0 pg/mL; P=0.026), and miR-155 (0.21 versus 0.16; P=0.015) levels than those without deposition findings. In asymptomatic individuals with chronic hyperuricemia, the presence of synovitis and double contour sign by US may represent a subclinical manifestation of monosodium urate crystals nucleation, capable of triggering inflammatory pathways (IL-6 and IL-8) and mechanisms of intercellular communication (miR-155) similar to what is observed in gout. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Efficacy of allopurinol and benzbromarone for the control of hyperuricaemia. A pathogenic approach to the treatment of primary chronic gout

PubMed Central

Perez-Ruiz, F; Alonso-Ruiz, A; Calabozo, M; Herrero-Beites, A; Garcia-Erauskin, G; Ruiz-Lucea, E

1998-01-01

OBJECTIVES—To study the efficacy of allopurinol and benzbromarone to reduce serum urate concentrations in patients with primary chronic gout.
METHODS—Prospective, parallel, open study of 86 consecutive male patients with primary chronic gout. Forty nine patients (26 normal excretors and 23 under excretors) were given allopurinol 300 mg/day and 37 under excretors benzbromarone 100 mg/day. After achieving steady plasma urate concentrations with such doses, treatment was then adjusted to obtain optimal plasmatic urate concentrations (under 6 mg/dl).
RESULTS—Patients receiving allopurinol 300 mg/day showed a mean reduction of plasmatic urate of 2.75 mg/dl (from 8.60 to 5.85 mg/dl) and 3.34 mg/dl (from 9.10 to 5.76 mg/dl) in normal excretors and under excretors respectively. Patients receiving benzbromarone 100 mg/day achieved a reduction of plasmatic urate of 5.04 mg/dl (from 8.58 to 3.54 mg/dl). Fifty three per cent of patients receiving allopurinol and 100% receiving benzbromarone achieved optimal plasma urate concentrations at such doses. The patients with poor results with allopurinol 300 mg/day achieved a proper plasma urate concentration with allopurinol 450 to 600 mg/day, the mean final dose being 372 mg/day. Renal fuction improved and no case of renal lithiasis was observed among benzbromarone treated patients, whose mean final dose was 76 mg/day.
CONCLUSION—Benzbromarone is very effective to control plasma urate concentrations at doses ranging from 50 to 100 mg/day. Uricosuric treatment is a suitable approach to the treatment of patients with gout who show underexcretion of urate.

 Keywords: gout; gout suppressants; allopurinol; benzbromarone PMID:9849314

Mendelian randomization analysis associates increased serum urate, due to genetic variation in uric acid transporters, with improved renal function.

PubMed

Hughes, Kim; Flynn, Tanya; de Zoysa, Janak; Dalbeth, Nicola; Merriman, Tony R

2014-02-01

Increased serum urate predicts chronic kidney disease independent of other risk factors. The use of xanthine oxidase inhibitors coincides with improved renal function. Whether this is due to reduced serum urate or reduced production of oxidants by xanthine oxidase or another physiological mechanism remains unresolved. Here we applied Mendelian randomization, a statistical genetics approach allowing disentangling of cause and effect in the presence of potential confounding, to determine whether lowering of serum urate by genetic modulation of renal excretion benefits renal function using data from 7979 patients of the Atherosclerosis Risk in Communities and Framingham Heart studies. Mendelian randomization by the two-stage least squares method was done with serum urate as the exposure, a uric acid transporter genetic risk score as instrumental variable, and estimated glomerular filtration rate and serum creatinine as the outcomes. Increased genetic risk score was associated with significantly improved renal function in men but not in women. Analysis of individual genetic variants showed the effect size associated with serum urate did not correlate with that associated with renal function in the Mendelian randomization model. This is consistent with the possibility that the physiological action of these genetic variants in raising serum urate correlates directly with improved renal function. Further studies are required to understand the mechanism of the potential renal function protection mediated by xanthine oxidase inhibitors.

Hyperuricemia, Acute and Chronic Kidney Disease, Hypertension, and Cardiovascular Disease: Report of a Scientific Workshop Organized by the National Kidney Foundation.

PubMed

Johnson, Richard J; Bakris, George L; Borghi, Claudio; Chonchol, Michel B; Feldman, David; Lanaspa, Miguel A; Merriman, Tony R; Moe, Orson W; Mount, David B; Sanchez Lozada, Laura Gabriella; Stahl, Eli; Weiner, Daniel E; Chertow, Glenn M

2018-06-01

Urate is a cause of gout, kidney stones, and acute kidney injury from tumor lysis syndrome, but its relationship to kidney disease, cardiovascular disease, and diabetes remains controversial. A scientific workshop organized by the National Kidney Foundation was held in September 2016 to review current evidence. Cell culture studies and animal models suggest that elevated serum urate concentrations can contribute to kidney disease, hypertension, and metabolic syndrome. Epidemiologic evidence also supports elevated serum urate concentrations as a risk factor for the development of kidney disease, hypertension, and diabetes, but differences in methodologies and inpacts on serum urate concentrations by even subtle changes in kidney function render conclusions uncertain. Mendelian randomization studies generally do not support a causal role of serum urate in kidney disease, hypertension, or diabetes, although interpretation is complicated by nonhomogeneous populations, a failure to consider environmental interactions, and a lack of understanding of how the genetic polymorphisms affect biological mechanisms related to urate. Although several small clinical trials suggest benefits of urate-lowering therapies on kidney function, blood pressure, and insulin resistance, others have been negative, with many trials having design limitations and insufficient power. Thus, whether uric acid has a causal role in kidney and cardiovascular diseases requires further study. Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Data Analysis Tools for Visualization Study

DTIC Science & Technology

2015-08-01

34The line is darker."],Ŗ":[99,130,58,"Other countries trying to connect directly with the US."],ŗ":[57,94,105,107,109,131,30,41,47,68,72,124,"Too... countries . . . | 3 98335 | MSU | 16 | nodelink | 16:51:42 | 130 | 2 | Other countries . . . | 3 98336...MSU | 16 | nodelink | 16:51:42 | 58 | 2 | Other countries . . . | 3 98337 | MSU | 16 | nodelink

Serum urate and the risk of major coronary heart disease events.

PubMed Central

Wannamethee, S. G.; Shaper, A. G.; Whincup, P. H.

1997-01-01

OBJECTIVE: To examine the relation between serum urate and the risk of major coronary heart disease events. DESIGN: A prospective study of a male cohort. SETTING: One general practice in each of 24 British towns. SUBJECTS: 7688 men aged 40-59 years at screening. MAIN OUTCOME MEASURES: Fatal and non-fatal coronary heart disease events. RESULTS: There were 1085 major coronary heart disease events during the average follow up period of 16.8 years. Serum urate was significantly associated with a wide range of cardiovascular risk factors including body mass index, alcohol intake, antihypertensive treatment, pre-existing coronary heart disease, serum triglycerides, cholesterol, and diastolic blood pressure. There was a significant positive association between serum urate and risk of coronary heart disease after adjustment for lifestyle factors and disease indicators. This relation was attenuated to non-significance upon additional adjustment for diastolic blood pressure and serum total cholesterol: cholesterol appeared to be the critical factor in attenuating this relation. When the association between serum urate and risk of coronary heart disease was examined by presence and grade of pre-existing coronary heart disease, a positive association was seen only in men with previous definite myocardial infarction, even after full adjustment (P = 0.07). CONCLUSIONS: The relation between serum urate and the risk of coronary heart disease depends heavily upon the presence of pre-existing myocardial infarction and widespread underlying atherosclerosis as well as the clustering of risk factors. Thus serum urate is not a truly independent risk factor for coronary heart disease. Raised serum urate appears to be an integral part of the cluster of risk factors associated with the insulin resistance syndrome that include obesity, raised serum triglycerides, and serum cholesterol. PMID:9326988

MSU Antenna Pattern Data

NASA Technical Reports Server (NTRS)

Mo, Tsan; Kleespies, Thomas J.; Green, J. Philip

2000-01-01

The Microwave Sounding Unit (MSU) antenna pattern data for nine MSU Flight Models (FMs) have been successfully rescued from 22-year old 7-track and 9-track magnetic tapes and cartridges. These antenna pattern data were unpacked into user-friendly ASCII format, and are potentially useful for making antenna pattern corrections to MSU antenna temperatures in retrieving the true brightness temperatures. We also properly interpreted the contents of the data and show how to convert the measured antenna signal amplitude in volts into relative antenna power in dB with proper normalization. It is found that the data are of high quality with a 60-dB drop in the co-polarized antenna patterns from the central peak value to its side-lobe regions at scan angles beyond 30 deg. The unpacked antenna pattern data produced in this study provide a useful database for data users to correct the antenna side-lobe contribution to MSU measurements. All of the data are available to the scientific community on a single CD-ROM.

Treat-to-target (T2T) recommendations for gout.

PubMed

Kiltz, U; Smolen, J; Bardin, T; Cohen Solal, A; Dalbeth, N; Doherty, M; Engel, B; Flader, C; Kay, J; Matsuoka, M; Perez-Ruiz, F; da Rocha Castelar-Pinheiro, G; Saag, K; So, A; Vazquez Mellado, J; Weisman, M; Westhoff, T H; Yamanaka, H; Braun, J

2017-04-01

The treat-to-target (T2T) concept has been applied successfully in several inflammatory rheumatic diseases. Gout is a chronic disease with a high burden of pain and inflammation. Because the pathogenesis of gout is strongly related to serum urate levels, gout may be an ideal disease in which to apply a T2T approach. Our aim was to develop international T2T recommendations for patients with gout. A committee of experts with experience in gout agreed upon potential targets and outcomes, which was the basis for the systematic literature search. Eleven rheumatologists, one cardiologist, one nephrologist, one general practitioner and one patient met in October 2015 to develop T2T recommendations based on the available scientific evidence. Levels of evidence, strength of recommendations and levels of agreement were derived. Although no randomised trial was identified in which a comparison with standard treatment or an evaluation of a T2T approach had been performed in patients with gout, indirect evidence was provided to focus on targets such as normalisation of serum urate levels. The expert group developed four overarching principles and nine T2T recommendations. They considered dissolution of crystals and prevention of flares to be fundamental; patient education, ensuring adherence to medications and monitoring of serum urate levels were also considered to be of major importance. This is the first application of the T2T approach developed for gout. Since no publication reports a trial comparing treatment strategies for gout, highly credible overarching principles and level D expert recommendations were created and agreed upon. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Renal Transport of Uric Acid: Evolving Concepts and Uncertainties

PubMed Central

Bobulescu, Ion Alexandru; Moe, Orson W.

2013-01-01

In addition to its role as a metabolic waste product, uric acid has been proposed to be an important molecule with multiple functions in human physiology and pathophysiology and may be linked to human diseases beyond nephrolithiasis and gout. Uric acid homeostasis is determined by the balance between production, intestinal secretion, and renal excretion. The kidney is an important regulator of circulating uric acid levels, by reabsorbing around 90% of filtered urate, while being responsible for 60–70% of total body uric acid excretion. Defective renal handling of urate is a frequent pathophysiologic factor underpinning hyperuricemia and gout. In spite of tremendous advances over the past decade, the molecular mechanisms of renal urate transport are still incompletely understood. Many transport proteins are candidate participants in urate handling, with URAT1 and GLUT9 being the best characterized to date. Understanding these transporters is increasingly important for the practicing clinician as new research unveils their physiology, importance in drug action, and genetic association with uric acid levels in human populations. The future may see the introduction of new drugs that specifically act on individual renal urate transporters for the treatment of hyperuricemia and gout. PMID:23089270

Brain Imaging Using Mobile CT: Current Status and Future Prospects.

PubMed

John, Seby; Stock, Sarah; Cerejo, Russell; Uchino, Ken; Winners, Stacey; Russman, Andrew; Masaryk, Thomas; Rasmussen, Peter; Hussain, Muhammad S

2016-01-01

Computed tomography (CT) is an invaluable tool in the diagnosis of many clinical conditions. Several advancements in biomedical engineering have achieved increase in speed, improvements in low-contrast detectability and image quality, and lower radiation. Portable or mobile CT constituted one such important advancement. It is especially useful in evaluating critically ill, intensive care unit patients by scanning them at bedside. A paradigm shift in utilization of mobile CT was its installation in ambulances for the management of acute stroke. Given the time sensitive nature of acute ischemic stroke, Mobile stroke units (MSU) were developed in Germany consisting of an ambulance equipped with a CT scanner, point of care laboratory system, along with teleradiological support. In a radical reconfiguration of stroke care, the MSU would bring the CT scanner to the stroke patient, without waiting for the patient at the emergency room. Two separate MSU projects in Saarland and Berlin demonstrated the safety and feasibility of this concept for prehospital stroke care, showing increased rate of intravenous thrombolysis and significant reduction in time to treatment compared to conventional care. MSU also improved the triage of patients to appropriate and specialized hospitals. Although multiple issues remain yet unanswered with the MSU concept including clinical outcome and cost-effectiveness, the MSU venture is visionary and enables delivery of life-saving and enhancing treatment for ischemic and hemorrhagic stroke. In this review, we discuss the development of mobile CT and its applications, with specific focus on its use in MSUs along with our institution's MSU experience. Copyright © 2015 by the American Society of Neuroimaging.

Mobile Simulation Unit: taking simulation to the surgical trainee.

PubMed

Pena, Guilherme; Altree, Meryl; Babidge, Wendy; Field, John; Hewett, Peter; Maddern, Guy

2015-05-01

Simulation-based training has become an increasingly accepted part of surgical training. However, simulators are still not widely available to surgical trainees. Some factors that hinder the widespread implementation of simulation-based training are the lack of standardized methods and equipment, costs and time constraints. We have developed a Mobile Simulation Unit (MSU) that enables trainees to access modern simulation equipment tailored to the needs of the learner at the trainee's workplace. From July 2012 to December 2012, the MSU visited six hospitals in South Australia, four in metropolitan and two in rural areas. Resident Medical Officers, surgical trainees, Fellows and International Medical Graduates were invited to voluntarily utilize a variety of surgical simulators on offer. Participants were asked to complete a survey about the accessibility of simulation equipment at their workplace, environment of the MSU, equipment available and instruction received. Utilization data were collected. The MSU was available for a total of 303 h over 52 days. Fifty-five participants were enrolled in the project and each spent on average 118 min utilizing the simulators. The utilization of the total available time was 36%. Participants reported having a poor access to simulation at their workplace and overwhelmingly gave positive feedback regarding their experience in the MSU. The use of the MSU to provide simulation-based education in surgery is feasible and practical. The MSU provides consistent simulation training at the surgical trainee's workplace, regardless of geographic location, and it has the potential to increase participation in simulation programmes. © 2014 Royal Australasian College of Surgeons.

Temporal and Spatial Flap Variability in Laser In-Situ Keratomileusis by Optical Coherence Tomography.

PubMed

Dawood, Yousif Farhan; Al Hassany, Usama; Issa, Ammar F

2017-01-01

To study changes in flap thickness made with two different microkeratome heads across different corneal locations using anterior segment optical coherence tomography (OCT). In this prospective, non-randomized, consecutive case series, subjects who had their laser in-situ keratomileusis (LASIK) flaps made using 90 μm (MSU90) or 130 μm (MSU130) disposable M2 microkeratome heads were examined using OCT. The measurements were performed at three locations (central and 2.5 mm to either side) at 1 day, 1 week, and 1 month postoperatively. The central flap thickness was 123 ± 15, 130 ± 14, and 127 ± 13 μm, respectively, at 1 day, 1 week, and 1 month postoperatively in the MSU90 group (41 eyes) and 142 ± 20, 147 ± 19, and 143 ± 15 μm, respectively, in the MSU130 group (47 eyes). At 1 month, peripheral flap thickness was 161 ± 17 and 159 ± 13 μm, respectively, at 2.5 mm to the right and left of corneal center in the MSU90 group. The corresponding figures were 170 ± 14 and 167 ± 13 μm, respectively, in the MSU130 group. There was a statistically significant difference between the two groups at all locations ( P < 0.001). No statistically significant change in flap thickness was detected in either group at any assessment time. There was a partial positive correlation (after controlling for preoperative manifest refractive spherical equivalent) between central flap thickness and preoperative ultrasound central pachymetry ( r = 0.739, P = 0.036) in the MSU90 group but not in the MSU130 group. Using OCT, changes in flap thickness were minimal in the first month after LASIK. Flap thickness correlated strongly with central corneal thickness if a 90 μm head was used.

Clinical Information Systems Integration in New York City's First Mobile Stroke Unit.

PubMed

Kummer, Benjamin R; Lerario, Michael P; Navi, Babak B; Ganzman, Adam C; Ribaudo, Daniel; Mir, Saad A; Pishanidar, Sammy; Lekic, Tim; Williams, Olajide; Kamel, Hooman; Marshall, Randolph S; Hripcsak, George; Elkind, Mitchell S V; Fink, Matthew E

2018-01-01

Mobile stroke units (MSUs) reduce time to thrombolytic therapy in acute ischemic stroke. These units are widely used, but the clinical information systems underlying MSU operations are understudied. The first MSU on the East Coast of the United States was established at New York Presbyterian Hospital (NYP) in October 2016. We describe our program's 7-month pilot, focusing on the integration of our hospital's clinical information systems into our MSU to support patient care and research efforts. NYP's MSU was staffed by two paramedics, one radiology technologist, and a vascular neurologist. The unit was equipped with four laptop computers and networking infrastructure enabling all staff to access the hospital intranet and clinical applications during operating hours. A telephone-based registration procedure registered patients from the field into our admit/discharge/transfer system, which interfaced with the institutional electronic health record (EHR). We developed and implemented a computerized physician order entry set in our EHR with prefilled values to permit quick ordering of medications, imaging, and laboratory testing. We also developed and implemented a structured clinician note to facilitate care documentation and clinical data extraction. Our MSU began operating on October 3, 2016. As of April 27, 2017, the MSU transported 49 patients, of whom 16 received tissue plasminogen activator (t-PA). Zero technical problems impacting patient care were reported around registration, order entry, or intranet access. Two onboard network failures occurred, resulting in computed tomography scanner malfunctions, although no patients became ineligible for time-sensitive treatment as a result. Thirteen (26.5%) clinical notes contained at least one incomplete time field. The main technical challenges encountered during the integration of our hospital's clinical information systems into our MSU were onboard network failures and incomplete clinical documentation. Future studies are necessary to determine whether such integrative efforts improve MSU care quality, and which enhancements to information systems will optimize clinical care and research efforts. Schattauer GmbH Stuttgart.

World's First 24/7 Mobile Stroke Unit: Initial 6-Month Experience at Mercy Health in Toledo, Ohio.

PubMed

Lin, Eugene; Calderon, Victoria; Goins-Whitmore, Julie; Bansal, Vibhav; Zaidat, Osama

2018-01-01

As the fourth mobile stroke unit (MSU) in the nation, and the first 24/7 unit worldwide, we review our initial experience with the Mercy Health MSU and institutional protocols implemented to facilitate rapid treatment of acute stroke patients and field triage for patients suffering other time-sensitive, acute neurologic emergencies in Lucas County, Ohio, and the greater Toledo metropolitan area. Data was prospectively collected for all patients transported and treated by the MSU during the first 6 months of service. Data was abstracted from documentation of on-scene emergency medical services (EMS) personnel, critical care nurses, and onboard physicians, who participated through telemedicine. The MSU was dispatched 248 times and transported 105 patients after on-scene examination with imaging. Intravenous (IV) tissue plasminogen activator (tPA) was administered to 10 patients; 8 patients underwent successful endovascular therapy after a large vessel occlusion was identified using CT performed within the MSU without post treatment symptomatic hemorrhage. Moreover, 14 patients were treated with IV anti-epileptics for status epilepticus, and 19 patients received IV anti-hypertensive agents for malignant hypertension. MSU alarm to on-scene times and treatment times were 34.7 min (25-49) and 50.6 min (44.4-56.8), respectively. The world's first 24/7 MSU has been successfully implemented with IV-tPA administration rates and times comparable to other MSUs nation-wide, while demonstrating rapid triage and treatment in the field for neurologic emergencies, including status epilepticus. With the rising number of MSUs worldwide, further data will drive standardized protocols that can be adopted nationwide by EMS.

Inference of Global Mean Temperature Trend and Climate Change from MSU and AMSU

NASA Technical Reports Server (NTRS)

Prabhakara, Cuddapah; Iacovazzi, R. A., Jr.; Yoo, J.-M.; Lau, William K. M. (Technical Monitor)

2001-01-01

Microwave Sounding Unit (MSU) and Advanced MSU (AMSU) radiometers flown on the NOAA operational satellite series are potentially valuable as global temperature monitoring devices. Spencer and Christy pioneered the analysis of mid-tropospheric temperature, given by MSU Channel 2 (Ch 2) at 53.74 GHz, to derive the global temperature trend. Also, in addition to monitoring global temperature, these microwave radiometers have the potential to reveal interannual climate signals in tropics. We have analyzed the data of MSU Ch 2 and AMSU Ch 5 (53.6 GHz) from the NOAA operational satellites for the period 1980 to 2000, utilizing the NOAA calibration procedure. The data are corrected for the satellite orbital drift based on the temporal changes of the on-board warm blackbody temperature. From our analysis, we find that the global temperature increased at a rate of 0.13 +/- 0.05 Kdecade(sup -1) during 1980 to 2000. From an Empirical Orthogonal Function (EOF) analysis of the MSU global data, we find that the mid-tropospheric temperature in middle and high latitudes responds to the ENSO forcing during the Northern Hemisphere Winter in a distinct manner. This mid-latitude response is opposite in phase to that in the tropics. This result is in accord with simulations performed with an ECMWF global spectral model. This study shows a potential use of the satellite observations for climatic change.

Gout: A Disease of Kings.

PubMed

Tang, Sydney C W

2018-01-01

As a disease of kings, and the king of diseases, gout is one of the oldest joint diseases known to humans. First described as far back as 2640 B.C., gout is still the most common form of inflammatory arthritis haunting humans in the 21st century. The disease is caused by the chronic elevation of serum uric acid levels above the saturation point for monosodium urate crystal formation. Its incidence is progressively rising even today, but there are also regional and ethnic variations. Finally, the role of genetics is only beginning to be unraveled. © 2018 S. Karger AG, Basel.

Coexistence of Sarcoidosis and Gouty Arthritis.

PubMed

Semiz, Hüseyin; Kobak, Senol

2017-08-21

Sarcoidosis is an inflammatory disease with unknown cause characterized by non-caseating granuloma formations. It may present with bilateral hilar lymphadenopathy, skin lesions, the involvement of eye and symptoms on the locomotor system. Gouty arthritis is an autoinflammatory disease characterized by hyperuricemia, recurrent arthritis attacks and the deposition of monosodium urate crystals in the joints and the surrounding tissues. We reported the coexistence of sarcoidosis and gouty arthritis in this paper. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

The genetics of hyperuricaemia and gout.

PubMed

Reginato, Anthony M; Mount, David B; Yang, Irene; Choi, Hyon K

2012-10-01

Gout is a common and very painful inflammatory arthritis caused by hyperuricaemia. This review provides an update on the genetics of hyperuricaemia and gout, including findings from genome-wide association studies. Most of the genes that associated with serum uric acid levels or gout are involved in the renal urate-transport system. For example, the urate transporter genes SLC2A9, ABCG2 and SLC22A12 modulate serum uric acid levels and gout risk. The net balance between renal urate absorption and secretion is a major determinant of serum uric acid concentration and loss-of-function mutations in SLC2A9 and SLC22A12 cause hereditary hypouricaemia due to reduced urate absorption and unopposed urate secretion. However, the variance in serum uric acid explained by genetic variants is small and their clinical utility for gout risk prediction seems limited because serum uric acid levels effectively predict gout risk. Urate-associated genes and genetically determined serum uric acid levels were largely unassociated with cardiovascular-metabolic outcomes, challenging the hypothesis of a causal role of serum uric acid in the development of cardiovascular disease. Strong pharmacogenetic associations between HLA-B*5801 alleles and severe allopurinol-hypersensitivity reactions were shown in Asian and European populations. Genetic testing for HLA-B*5801 alleles could be used to predict these potentially fatal adverse effects.

The dynamics of chronic gout treatment: medication gaps and return to therapy.

PubMed

Harrold, Leslie R; Andrade, Susan E; Briesacher, Becky; Raebel, Marsha A; Fouayzi, Hassan; Yood, Robert A; Ockene, Ira S

2010-01-01

To identify gaps in therapy with urate-lowering drugs for the treatment of gout as well as factors associated with resuming therapy. From 2 integrated delivery systems, we identified patients 18 years or older with a diagnosis of gout who initiated use of a urate-lowering drug from January 1, 2000 through June 30, 2006 and who had a gap in therapy. A gap was defined as a period of over 60 days after the completion of 1 prescription in which no refill for a urate-lowering drug was obtained. Survival curves were used to assess return to therapy of urate-lowering drugs. Cox proportional hazards analysis estimated the association between covariates and return to therapy. There were 4166 new users of urate-lowering drugs (97% received allopurinol), of whom 2929 (70%) had a gap in therapy. Among those with a gap, in 75% it occurred in the first year of therapy. Fifty percent of patients with a gap returned to therapy within 8 months, and by 4 years it was 75%. Age 45-74 years (<45 referent) and greater duration of urate-lowering drug use before the gap was associated with resuming treatment within 1 year. In contrast, receipt of nonsteroidal anti-inflammatory drugs or glucocorticoids in the year before the gap was associated with a reduced likelihood of resuming therapy. The majority of gout patients with gaps in urate-lowering drug use returned to treatment. More investigation is needed to better understand why patients may go for months without refilling prescriptions, given the clinical consequences of nonadherence. Copyright 2010 Elsevier Inc. All rights reserved.

Using serum urate as a validated surrogate end point for flares in patients with gout: protocol for a systematic review and meta-regression analysis

PubMed Central

Morillon, Melanie B; Stamp, Lisa; Taylor, William; Fransen, Jaap; Dalbeth, Nicola; Singh, Jasvinder A; Lassere, Marissa

2016-01-01

Introduction Gout is the most common inflammatory arthritis in men over 40 years of age. Long-term urate-lowering therapy is considered a key strategy for effective gout management. The primary outcome measure for efficacy in clinical trials of urate-lowering therapy is serum urate levels, effectively acting as a surrogate for patient-centred outcomes such as frequency of gout attacks or pain. Yet it is not clearly demonstrated that the strength of the relationship between serum urate and clinically relevant outcomes is sufficiently strong for serum urate to be considered an adequate surrogate. Our objective is to investigate the strength of the relationship between changes in serum urate in randomised controlled trials and changes in clinically relevant outcomes according to the ‘Biomarker-Surrogacy Evaluation Schema version 3’ (BSES3), documenting the validity of selected instruments by applying the ‘OMERACT Filter 2.0’. Methods and analysis A systematic review described in terms of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines will identify all relevant studies. Standardised data elements will be extracted from each study by 2 independent reviewers and disagreements are resolved by discussion. The data will be analysed by meta-regression of the between-arm differences in the change in serum urate level (independent variable) from baseline to 3 months (or 6 and 12 months if 3-month values are not available) against flare rate, tophus size and number and pain at the final study visit (dependent variables). Ethics and dissemination This study will not require specific ethics approval since it is based on analysis of published (aggregated) data. The intended audience will include healthcare researchers, policymakers and clinicians. Results of the study will be disseminated by peer-reviewed publications. Trial registration number CRD42016026991. PMID:27650765

Quantitative analysis with advanced compensated polarized light microscopy on wavelength dependence of linear birefringence of single crystals causing arthritis

NASA Astrophysics Data System (ADS)

Takanabe, Akifumi; Tanaka, Masahito; Taniguchi, Atsuo; Yamanaka, Hisashi; Asahi, Toru

2014-07-01

To improve our ability to identify single crystals causing arthritis, we have developed a practical measurement system of polarized light microscopy called advanced compensated polarized light microscopy (A-CPLM). The A-CPLM system is constructed by employing a conventional phase retardation plate, an optical fibre and a charge-coupled device spectrometer in a polarized light microscope. We applied the A-CPLM system to measure linear birefringence (LB) in the visible region, which is an optical anisotropic property, for tiny single crystals causing arthritis, i.e. monosodium urate monohydrate (MSUM) and calcium pyrophosphate dihydrate (CPPD). The A-CPLM system performance was evaluated by comparing the obtained experimental data using the A-CPLM system with (i) literature data for a standard sample, MgF2, and (ii) experimental data obtained using an established optical method, high-accuracy universal polarimeter, for the MSUM. The A-CPLM system was found to be applicable for measuring the LB spectra of the single crystals of MSUM and CPPD, which cause arthritis, in the visible regions. We quantitatively reveal the large difference in LB between MSUM and CPPD crystals. These results demonstrate the usefulness of the A-CPLM system for distinguishing the crystals causing arthritis.

US 93 north wildlife-vehicle collision and wildlife crossing monitoring.

DOT National Transportation Integrated Search

2015-01-01

Human safety: Wildlife-vehicle collisions : Habitat connectivity: Wildlife use crossing structures : Cost-benefit analyses : Contract research : WTI-MSU and CSKT : Students and other partners at MSU and UofM

Association analysis of the beta-3 adrenergic receptor Trp64Arg (rs4994) polymorphism with urate and gout.

PubMed

Fatima, Tahzeeb; Altaf, Sara; Phipps-Green, Amanda; Topless, Ruth; Flynn, Tanya J; Stamp, Lisa K; Dalbeth, Nicola; Merriman, Tony R

2016-02-01

The Arg64 allele of variant rs4994 (Trp64Arg) in the β3-adrenergic receptor gene has been associated with increased serum urate and risk of gout. Our objective was to investigate the relationship of rs4994 with serum urate and gout in New Zealand European, Māori and Pacific subjects. A total of 1730 clinically ascertained gout cases and 2145 controls were genotyped for rs4994 by Taqman(®). Māori and Pacific subjects were subdivided into Eastern Polynesian (EP) and Western Polynesian (WP) sample sets. Publicly available genotype data from the Atherosclerosis Risk in Communities Study and the Framingham Heart Study were utilized for serum urate association analysis. Multivariate logistic and linear regression adjusted for potential confounders was carried out using R version 2.15.2. No significant association of the minor Arg64 (G) allele of rs4994 with gout was found in the combined Polynesian cohorts (OR = 0.98, P = 0.88), although there was evidence, after adjustment for renal disease, for association in both the WP (OR = 0.53, P = 0.03) and the lower Polynesian ancestry EP sample sets (OR = 1.86, P = 0.05). There was no evidence for association with gout in the European sample set (OR = 1.11, P = 0.57). However, the Arg64 allele was positively associated with urate in the WP data set (β = 0.036, P = 0.004, P Corrected = 0.032). Association of the Arg64 variant with increased urate in the WP sample set was consistent with the previous literature, although the protective effect of this variant with gout in WP was inconsistent. This association provides an etiological link between metabolic syndrome components and urate homeostasis.

The genetics of hyperuricaemia and gout

PubMed Central

Reginato, Anthony M.; Mount, David B.; Yang, Irene; Choi, Hyon K.

2013-01-01

Gout is a common and very painful inflammatory arthritis caused by hyperuricaemia. This Review provides an update on the genetics of hyperuricaemia and gout, including findings from genome-wide association studies. Most of the genes that associated with serum uric acid levels or gout are involved in the renal urate-transport system. For example, the urate transporter genes SLC2A9, ABCG2 and SLC22A12 modulate serum uric acid levels and gout risk. The net balance between renal urate absorption and secretion is a major determinant of serum uric acid concentration and loss-of-function mutations in SLC2A9 and SLC22A12 cause hereditary hypouricaemia due to reduced urate absorption and unopposed urate secretion. However, the variance in serum uric acid explained by genetic variants is small and their clinical utility for gout risk prediction seems limited because serum uric acid levels effectively predict gout risk. Urate-associated genes and genetically determined serum uric acid levels were largely unassociated with cardiovascular–metabolic outcomes, challenging the hypothesis of a causal role of serum uric acid in the development of cardiovascular disease. Strong pharmacogenetic associations between HLA-B*5801 alleles and severe allopurinol-hypersensitivity reactions were shown in Asian and European populations. Genetic testing for HLA-B*5801 alleles could be used to predict these potentially fatal adverse effects. PMID:22945592

Urate levels predict survival in amyotrophic lateral sclerosis: Analysis of the expanded Pooled Resource Open-Access ALS clinical trials database.

PubMed

Paganoni, Sabrina; Nicholson, Katharine; Chan, James; Shui, Amy; Schoenfeld, David; Sherman, Alexander; Berry, James; Cudkowicz, Merit; Atassi, Nazem

2018-03-01

Urate has been identified as a predictor of amyotrophic lateral sclerosis (ALS) survival in some but not all studies. Here we leverage the recent expansion of the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database to study the association between urate levels and ALS survival. Pooled data of 1,736 ALS participants from the PRO-ACT database were analyzed. Cox proportional hazards regression models were used to evaluate associations between urate levels at trial entry and survival. After adjustment for potential confounders (i.e., creatinine and body mass index), there was an 11% reduction in risk of reaching a survival endpoint during the study with each 1-mg/dL increase in uric acid levels (adjusted hazard ratio 0.89, 95% confidence interval 0.82-0.97, P < 0.01). Our pooled analysis provides further support for urate as a prognostic factor for survival in ALS and confirms the utility of the PRO-ACT database as a powerful resource for ALS epidemiological research. Muscle Nerve 57: 430-434, 2018. © 2017 Wiley Periodicals, Inc.

A biohybrid hydrogel for the urate-responsive release of urate oxidase.

PubMed

Geraths, Christian; Daoud-El Baba, Marie; Charpin-El Hamri, Ghislaine; Weber, Wilfried

2013-10-10

Functional biomaterials that detect and correct pathological parameters hold high promises for biomedical application. In this study we describe a biohybrid hydrogel that detects elevated concentrations of uric acid and responds by dissolution and the release of uric acid-degrading urate oxidase. This material was synthesized by incorporating PEG-stabilized urate oxidase into a polyacrylamide hydrogel that was crosslinked by the uric acid-sensitive interaction between the uric acid transcription factor HucR and its operator hucO. We characterize the uric acid responsiveness of the material and demonstrate that it can effectively be applied to counteract flares of uric acid in a mouse model. This approach might be a first step towards a biomedical device autonomously managing uric acid burst associated to gouty arthritis and the tumor lysis syndrome. © 2013.

VizieR Online Data Catalog: The URAT Parallax Catalog (UPC). Update 2018 (Finch+, 2018)

NASA Astrophysics Data System (ADS)

Finch, C. T.; Zacharias, N.; Jao, W.-C.

2018-03-01

United States Naval Observatory (USNO) Robotic Astrometric Telescope (URAT) Parallax Catalog south (UPCs) and north (UPCn). These data are based on the accepted paper for the Astronomical Journal (2018) by C. Finch, N. Zacharias, and W.-C. Jao, "URAT south parallax results: discovery of new nearby stars" (2018AJ....155..176F). The southern data are new, while the northern data contain a subset of the previously published UPC catalog after applying the more stringent selection criteria of the south data and supplementing the data with columns of the southern data. The previously published URAT Parallax Catalog (UPC) paper is: C. Finch and N. Zacharias (2016AJ....151..160F, Cat. J/AJ/151/160) (arXiv:1604.06739). (3 data files).

Imaging birefringent crystals using micro optical coherence tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sharma, Gargi; Singh, Kanwarpal; Gardecki, Joseph A.; Tearney, Guillermo J.

2017-02-01

Background: Uric acid crystals have recently been identified as a possible therapeutic target for coronary artery disease. Being subcellular in size, it is difficult to identify these crystals in situ. Micro optical coherence tomography (Micro-OCT) allows one to image subcellular structures with 1-micron resolution. Even though Micro-OCT should be capable of resolving urate crystals, it's difficult to differentiate these structures from other scattering particles within tissue. In this work we developed a novel polarization sensitive micro OCT (ps-Micro-OCT) system for identification of uric acid crystals. Methods: A spectrometer based ps-Micro-OCT system was developed using a broadband light source. The broadband input light was divided into reference and sample signals using a beam splitter. The reference signal was further divided into two polarized signals with different polarization states. Reflected reference and sample signals were combined and sent to a spectrometer that recorded the interference signal. Results: To test the performance of system, a mirror was used as sample and a quarter wave-plate was placed in the sample path. The measured quarter wave-plate angle values matched closely to actual angle values. Next we prepared uric acid crystals in our lab and imaged them using this system.We were able to image and identify these crystals based on polarization measurements. Conclusion: In this work we imaged and identified uric acid crystals using a newly developed ps-Micro-OCT system. The proposed technique will enable imaging uric acid crystals in coronary artery.

Effectiveness of an electronic patient-centred self-management tool for gout sufferers: a cluster randomised controlled trial protocol.

PubMed

Day, Richard O; Frensham, Lauren J; Nguyen, Amy D; Baysari, Melissa T; Aung, Eindra; Lau, Annie Y S; Zwar, Nicholas; Reath, Jennifer; Laba, Tracey; Li, Ling; McLachlan, Andrew; Runciman, William B; Buchbinder, Rachelle; Clay-Williams, Robyn; Coiera, Enrico; Braithwaite, Jeffrey; McNeil, H Patrick; Hunter, David J; Pile, Kevin D; Portek, Ian; WIlliams, Kenneth Mapson; Westbrook, Johanna I

2017-10-16

Gout is increasing despite effective therapies to lower serum urate concentrations to 0.36 mmol/L or less, which, if sustained, significantly reduces acute attacks of gout. Adherence to urate-lowering therapy (ULT) is poor, with rates of less than 50% 1 year after initiation of ULT. Attempts to increase adherence in gout patients have been disappointing. We aim to evaluate the effectiveness of use of a personal, self-management, 'smartphone' application (app) to achieve target serum urate concentrations in people with gout. We hypothesise that personalised feedback of serum urate concentrations will improve adherence to ULT. Setting and designPrimary care. A prospective, cluster randomised (by general practitioner (GP) practices), controlled trial. GP practices will be randomised to either intervention or control clusters with their patients allocated to the same cluster. The intervention group will have access to the Healthy.me app tailored for the self-management of gout. The control group patients will have access to the same app modified to remove all functions except the Gout Attack Diary. The proportion of patients whose serum urate concentrations are less than or equal to 0.36 mmol/L after 6 months. Secondary outcomes will be proportions of patients achieving target urate concentrations at 12 months, ULT adherence rates, serum urate concentrations at 6 and 12 months, rates of attacks of gout, quality of life estimations and process and economic evaluations. The study is designed to detect a ≥30% improvement in the intervention group above the expected 50% achievement of target serum urate at 6 months in the control group: power 0.80, significance level 0.05, assumed 'dropout' rate 20%. This study has been approved by the University of New South Wales Human Research Ethics Committee. Study findings will be disseminated in international conferences and peer-reviewed journal. ACTRN12616000455460. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Effectiveness of an electronic patient-centred self-management tool for gout sufferers: a cluster randomised controlled trial protocol

PubMed Central

Frensham, Lauren J; Nguyen, Amy D; Baysari, Melissa T; Aung, Eindra; Lau, Annie Y S; Zwar, Nicholas; Reath, Jennifer; Li, Ling; McLachlan, Andrew; Runciman, William B; Buchbinder, Rachelle; Clay-Williams, Robyn; Braithwaite, Jeffrey; McNeil, H Patrick; Pile, Kevin D; Portek, Ian; WIlliams, Kenneth Mapson; Westbrook, Johanna I

2017-01-01

Introduction Gout is increasing despite effective therapies to lower serum urate concentrations to 0.36 mmol/L or less, which, if sustained, significantly reduces acute attacks of gout. Adherence to urate-lowering therapy (ULT) is poor, with rates of less than 50% 1 year after initiation of ULT. Attempts to increase adherence in gout patients have been disappointing. We aim to evaluate the effectiveness of use of a personal, self-management, ‘smartphone’ application (app) to achieve target serum urate concentrations in people with gout. We hypothesise that personalised feedback of serum urate concentrations will improve adherence to ULT. Methods and analysis Setting and design Primary care. A prospective, cluster randomised (by general practitioner (GP) practices), controlled trial. Participants GP practices will be randomised to either intervention or control clusters with their patients allocated to the same cluster. Intervention The intervention group will have access to the Healthy.me app tailored for the self-management of gout. The control group patients will have access to the same app modified to remove all functions except the Gout Attack Diary. Primary and secondary outcomes The proportion of patients whose serum urate concentrations are less than or equal to 0.36 mmol/L after 6 months. Secondary outcomes will be proportions of patients achieving target urate concentrations at 12 months, ULT adherence rates, serum urate concentrations at 6 and 12 months, rates of attacks of gout, quality of life estimations and process and economic evaluations. The study is designed to detect a ≥30% improvement in the intervention group above the expected 50% achievement of target serum urate at 6 months in the control group: power 0.80, significance level 0.05, assumed ‘dropout’ rate 20%. Ethics and dissemination This study has been approved by the University of New South Wales Human Research Ethics Committee. Study findings will be disseminated in international conferences and peer-reviewed journal. Trial registration number ACTRN12616000455460. PMID:29042386

Genetics of hyperuricemia and gout: implications for the present and future.

PubMed

George, Ronald L; Keenan, Robert T

2013-02-01

Gout is the most common inflammatory arthropathy and occurs in the setting of elevated serum urate levels. Gout is also known to be associated with multiple comorbidities including cardiovascular disease and the metabolic syndrome. Recent advances in research have increased our understanding and improved our knowledge of the pathophysiology of gout. Genome-wide association studies have permitted the identification of several new and common genetic factors that contribute to hyperuricemia and gout. Most of these are involved with the renal urate transport system (the uric acid transportasome), generally considered the most influential regulator of serum urate homeostasis. Thus far, SCL22A12, SCL2A9, and GLUT9 have been found to have the greatest variation and most influence on serum urate levels. However, genetics are only a part of the explanation in the development of hyperuricemia and gout. As results have been mixed, the role of known urate influential genes in gout's associated comorbidities remains unclear. Regardless, GWAS findings have expanded our understanding of the pathophysiology of hyperuricemia and gout, and will likely play a role in the development of future therapies and treatment of this ancient disease.

Effects of febuxostat on serum urate level in Japanese hyperuricemia patients.

PubMed

Yamamoto, Tetsuya; Hidaka, Yuji; Inaba, Masaaki; Ishimura, Eiji; Ooyama, Hiroshi; Kakuda, Hirokazu; Moriwaki, Yuji; Higami, Kenshi; Ohtawara, Akira; Hosoya, Tatsuo; Nishikawa, Hazime; Taniguchi, Atsuo; Ueda, Takanori; Yamauchi, Takahiro; Fujimori, Shin; Mineo, Ikuo; Yamanaka, Hisashi

2015-09-01

We assessed the efficacy and adverse effects of febuxostat in male hyperuricemia patients. This was a 12-week, multicenter, open-label, uncontrolled study. The enrolled subjects were 89 hyperuricemic male patients (12 overexcretors, 56 normal excretors, and 21 underexcretors). The endpoint was percent change in serum urate level. The concentration of urate in serum before and 12 weeks after beginning administration of febuxostat in the overexcretors was 9.34 ± 1.48 and 5.59 ± 1.17 mg/dl, respectively, while those were 8.59 ± 1.24 and 5.41 ± 1.35 mg/dl, respectively, in the normal excretors, and 8.29 ± 1.01and 5.11 ± 1.71 mg/dl, respectively, in the underexcretors. After 12 weeks, the rate of change in serum urate after beginning administration of febuxostat was - 0.384 ± 0.186 in the overexcretors, - 0.368 ± 0.128 in the normal excretors, and - 0.365 ± 0.217 in the underexcretors, with no significant differences among them. A common adverse event related to febuxostat was gout flare. Febuxostat effectively reduced the concentration of urate in serum in hyperuricemic patients regardless of the level of uric acid excreted in urine without severe adverse effects.

Parallax Results from URAT Epoch Data

NASA Astrophysics Data System (ADS)

Finch, Charlie T.; Zacharias, Norbert

2016-06-01

We present 1103 trigonometric parallaxes and proper motions from the United States Naval Observatory Robotic Astrometric Telescope (URAT) observations taken at the Naval Observatory Flagstaff Station (NOFS) over a three-year period from 2012 April to 2015 June covering the entire sky north of about -10^\\circ decl. We selected two samples: previously suspected nearby stars from known photometric distances and stars showing a large, significant parallax signature in URAT epoch data without any prior selection criteria. All systems presented in this paper have an observed parallax ≥40 mas with no previous published trigonometric parallax. The formal errors on these weighted parallax solutions are mostly between 4 and 10 mas. This sample gives a significant (of the order of 50%) increase to the number of known systems having a trigonometric parallax to be within 25 pc of the Sun (without applying Lutz-Kelker bias corrections). A few of these are found to be within 10 pc. Many of these new nearby stars display a total proper motion of less than 200 mas yr-1. URAT parallax results have been verified against Hipparcos and Yale data for stars in common. The publication of all signifigant parallax observations from URAT data is in preparation for CDS.

Calcium pyrophosphate dihydrate gout and other crystal deposition diseases.

PubMed

Reginato, A J

1991-08-01

The number of crystal or birefringent particles associated with arthritis is increasing, and a uniform taxonomy is needed. The term gout has been proposed as a generic term for these diseases based on historical, clinical, and crystallographic reasons. Calcium pyrophosphate dihydrate gout follows monosodium urate gout in frequency, and its spectrum of clinical manifestations continues to grow. Familial calcium pyrophosphate dihydrate gout was described for the first time in kindreds studied in England and Tunisia; new Jewish and Spanish kindreds were also reported. Type I collagen was shown to nucleate nativelike calcium pyrophosphate dihydrate crystals, and pyrophosphate elaboration was explored in cartilage explants in an attempt to reproduce the in vivo metabolic or endocrine disorders associated with calcium pyrophosphate dihydrate gout. The effect of pyrophosphatase and different cofactors such as magnesium in dissolving calcium pyrophosphate dihydrate crystals was investigated. High-resolution electron microscopy was used to study the interrelation between apatite and other basic calcium phosphate crystals in apatite gout. Raman microscopy was applied for the first time to identify crystals in biologic specimens. A simple and specific technique for basic calcium phosphate crystal identification is necessary to understand the relationship between different calcium phosphate crystals and osteoarthritis. Several reports about children and young patients with primary oxalate gout described the effect of oxalate on eyes, periodontal tissues, and bone. Multicenter studies showed poor results of renal transplantation, but favored combined liver and renal transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Simple Fabrication of a Highly Sensitive and Fast Glucose Biosensor using Enzyme Immobilized in Mesocellular Carbon Foam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Dohoon; Lee, Jinwoo; Kim, Jungbae

2005-12-05

We fabricated a highly sensitive and fast glucose biosensor by simply immobilizing glucose oxidase in mesocellular carbon foam. Due to its unique structure, the MSU-F-C enabled high enzyme loading without serious mass transfer limitation, resulting in high catalytic efficiency. As a result, the glucose biosensor fabricated with MSU-F-C/GOx showed a high sensitivity and fast response. Given these results and the inherent electrical conductivity, we anticipate that MSU-F-C will make a useful matrix for enzyme immobilization in various biocatalytic and electrobiocatalytic applications.

Achieving serum urate targets in gout: an audit in a gout-oriented rheumatology practice.

PubMed

Corbett, Elizabeth J M; Pentony, Peta; McGill, Neil W

2017-07-01

To assess the proportion of patients with gout who achieve target serum urate levels, the drug regime required and the reasons for failing to do so. We reviewed the files of all patients with gout who presented to a gout-oriented rheumatology practice between January 2010 and September 2014. Two hundred and thirty patients agreed to commence urate lowering therapy (ULT); 73% achieved their urate target, including 74% with non-tophaceous gout (target ≤ 0.36 mmol/L) and 71% with tophi (target ≤ 0.30 mmol/L). Of the 62 who failed to reach target, in 61 it was due to non-adherence and in one due to inefficacy. Adherence remains the major challenge to successful long-term gout management. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Streptomyces coelicolor encodes a urate-responsive transcriptional regulator with homology to PecS from plant pathogens.

PubMed

Huang, Hao; Mackel, Brian J; Grove, Anne

2013-11-01

Many transcriptional regulators control gene activity by responding to specific ligands. Members of the multiple-antibiotic resistance regulator (MarR) family of transcriptional regulators feature prominently in this regard, and they frequently function as repressors in the absence of their cognate ligands. Plant pathogens such as Dickeya dadantii encode a MarR homolog named PecS that controls expression of a gene encoding the efflux pump PecM in addition to other virulence genes. We report here that the soil bacterium Streptomyces coelicolor also encodes a PecS homolog (SCO2647) that regulates a pecM gene (SCO2646). S. coelicolor PecS, which exists as a homodimer, binds the intergenic region between pecS and pecM genes with high affinity. Several potential PecS binding sites were found in this intergenic region. The binding of PecS to its target DNA can be efficiently attenuated by the ligand urate, which also quenches the intrinsic fluorescence of PecS, indicating a direct interaction between urate and PecS. In vivo measurement of gene expression showed that activity of pecS and pecM genes is significantly elevated after exposure of S. coelicolor cultures to urate. These results indicate that S. coelicolor PecS responds to the ligand urate by attenuated DNA binding in vitro and upregulation of gene activity in vivo. Since production of urate is associated with generation of reactive oxygen species by xanthine dehydrogenase, we propose that PecS functions under conditions of oxidative stress.

Streptomyces coelicolor Encodes a Urate-Responsive Transcriptional Regulator with Homology to PecS from Plant Pathogens

PubMed Central

Huang, Hao; Mackel, Brian J.

2013-01-01

Many transcriptional regulators control gene activity by responding to specific ligands. Members of the multiple-antibiotic resistance regulator (MarR) family of transcriptional regulators feature prominently in this regard, and they frequently function as repressors in the absence of their cognate ligands. Plant pathogens such as Dickeya dadantii encode a MarR homolog named PecS that controls expression of a gene encoding the efflux pump PecM in addition to other virulence genes. We report here that the soil bacterium Streptomyces coelicolor also encodes a PecS homolog (SCO2647) that regulates a pecM gene (SCO2646). S. coelicolor PecS, which exists as a homodimer, binds the intergenic region between pecS and pecM genes with high affinity. Several potential PecS binding sites were found in this intergenic region. The binding of PecS to its target DNA can be efficiently attenuated by the ligand urate, which also quenches the intrinsic fluorescence of PecS, indicating a direct interaction between urate and PecS. In vivo measurement of gene expression showed that activity of pecS and pecM genes is significantly elevated after exposure of S. coelicolor cultures to urate. These results indicate that S. coelicolor PecS responds to the ligand urate by attenuated DNA binding in vitro and upregulation of gene activity in vivo. Since production of urate is associated with generation of reactive oxygen species by xanthine dehydrogenase, we propose that PecS functions under conditions of oxidative stress. PMID:23995633

Modulation of genetic associations with serum urate levels by body-mass-index in humans.

PubMed

Huffman, Jennifer E; Albrecht, Eva; Teumer, Alexander; Mangino, Massimo; Kapur, Karen; Johnson, Toby; Kutalik, Zoltán; Pirastu, Nicola; Pistis, Giorgio; Lopez, Lorna M; Haller, Toomas; Salo, Perttu; Goel, Anuj; Li, Man; Tanaka, Toshiko; Dehghan, Abbas; Ruggiero, Daniela; Malerba, Giovanni; Smith, Albert V; Nolte, Ilja M; Portas, Laura; Phipps-Green, Amanda; Boteva, Lora; Navarro, Pau; Johansson, Asa; Hicks, Andrew A; Polasek, Ozren; Esko, Tõnu; Peden, John F; Harris, Sarah E; Murgia, Federico; Wild, Sarah H; Tenesa, Albert; Tin, Adrienne; Mihailov, Evelin; Grotevendt, Anne; Gislason, Gauti K; Coresh, Josef; D'Adamo, Pio; Ulivi, Sheila; Vollenweider, Peter; Waeber, Gerard; Campbell, Susan; Kolcic, Ivana; Fisher, Krista; Viigimaa, Margus; Metter, Jeffrey E; Masciullo, Corrado; Trabetti, Elisabetta; Bombieri, Cristina; Sorice, Rossella; Döring, Angela; Reischl, Eva; Strauch, Konstantin; Hofman, Albert; Uitterlinden, Andre G; Waldenberger, Melanie; Wichmann, H-Erich; Davies, Gail; Gow, Alan J; Dalbeth, Nicola; Stamp, Lisa; Smit, Johannes H; Kirin, Mirna; Nagaraja, Ramaiah; Nauck, Matthias; Schurmann, Claudia; Budde, Kathrin; Farrington, Susan M; Theodoratou, Evropi; Jula, Antti; Salomaa, Veikko; Sala, Cinzia; Hengstenberg, Christian; Burnier, Michel; Mägi, Reedik; Klopp, Norman; Kloiber, Stefan; Schipf, Sabine; Ripatti, Samuli; Cabras, Stefano; Soranzo, Nicole; Homuth, Georg; Nutile, Teresa; Munroe, Patricia B; Hastie, Nicholas; Campbell, Harry; Rudan, Igor; Cabrera, Claudia; Haley, Chris; Franco, Oscar H; Merriman, Tony R; Gudnason, Vilmundur; Pirastu, Mario; Penninx, Brenda W; Snieder, Harold; Metspalu, Andres; Ciullo, Marina; Pramstaller, Peter P; van Duijn, Cornelia M; Ferrucci, Luigi; Gambaro, Giovanni; Deary, Ian J; Dunlop, Malcolm G; Wilson, James F; Gasparini, Paolo; Gyllensten, Ulf; Spector, Tim D; Wright, Alan F; Hayward, Caroline; Watkins, Hugh; Perola, Markus; Bochud, Murielle; Kao, W H Linda; Caulfield, Mark; Toniolo, Daniela; Völzke, Henry; Gieger, Christian; Köttgen, Anna; Vitart, Veronique

2015-01-01

We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.

Modulation of Genetic Associations with Serum Urate Levels by Body-Mass-Index in Humans

PubMed Central

Huffman, Jennifer E.; Albrecht, Eva; Teumer, Alexander; Mangino, Massimo; Kapur, Karen; Johnson, Toby; Kutalik, Zoltán; Pirastu, Nicola; Pistis, Giorgio; Lopez, Lorna M.; Haller, Toomas; Salo, Perttu; Goel, Anuj; Li, Man; Tanaka, Toshiko; Dehghan, Abbas; Ruggiero, Daniela; Malerba, Giovanni; Smith, Albert V.; Nolte, Ilja M.; Portas, Laura; Phipps-Green, Amanda; Boteva, Lora; Navarro, Pau; Johansson, Asa; Hicks, Andrew A.; Polasek, Ozren; Esko, Tõnu; Peden, John F.; Harris, Sarah E.; Murgia, Federico; Wild, Sarah H.; Tenesa, Albert; Tin, Adrienne; Mihailov, Evelin; Grotevendt, Anne; Gislason, Gauti K.; Coresh, Josef; D'Adamo, Pio; Ulivi, Sheila; Vollenweider, Peter; Waeber, Gerard; Campbell, Susan; Kolcic, Ivana; Fisher, Krista; Viigimaa, Margus; Metter, Jeffrey E.; Masciullo, Corrado; Trabetti, Elisabetta; Bombieri, Cristina; Sorice, Rossella; Döring, Angela; Reischl, Eva; Strauch, Konstantin; Hofman, Albert; Uitterlinden, Andre G.; Waldenberger, Melanie; Wichmann, H-Erich; Davies, Gail; Gow, Alan J.; Dalbeth, Nicola; Stamp, Lisa; Smit, Johannes H.; Kirin, Mirna; Nagaraja, Ramaiah; Nauck, Matthias; Schurmann, Claudia; Budde, Kathrin; Farrington, Susan M.; Theodoratou, Evropi; Jula, Antti; Salomaa, Veikko; Sala, Cinzia; Hengstenberg, Christian; Burnier, Michel; Mägi, Reedik; Klopp, Norman; Kloiber, Stefan; Schipf, Sabine; Ripatti, Samuli; Cabras, Stefano; Soranzo, Nicole; Homuth, Georg; Nutile, Teresa; Munroe, Patricia B.; Hastie, Nicholas; Campbell, Harry; Rudan, Igor; Cabrera, Claudia; Haley, Chris; Franco, Oscar H.; Merriman, Tony R.; Gudnason, Vilmundur; Pirastu, Mario; Penninx, Brenda W.; Snieder, Harold; Metspalu, Andres; Ciullo, Marina; Pramstaller, Peter P.; van Duijn, Cornelia M.; Ferrucci, Luigi; Gambaro, Giovanni; Deary, Ian J.; Dunlop, Malcolm G.; Wilson, James F.; Gasparini, Paolo; Gyllensten, Ulf; Spector, Tim D.; Wright, Alan F.; Hayward, Caroline; Watkins, Hugh; Perola, Markus; Bochud, Murielle; Kao, W. H. Linda; Caulfield, Mark; Toniolo, Daniela; Völzke, Henry; Gieger, Christian; Köttgen, Anna; Vitart, Veronique

2015-01-01

We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment. PMID:25811787

The high affinity of small-molecule antioxidants for hemoglobin.

PubMed

Puscas, Cristina; Radu, Luana; Carrascoza, Francisco; Mot, Augustin C; Amariei, Diana; Lungu, Oana; Scurtu, Florina; Podea, Paula; Septelean, Raluca; Matei, Alina; Mic, Mihaela; Attia, Amr A; Silaghi-Dumitrescu, Radu

2018-06-18

Hemoglobin has previously been shown to display ascorbate peroxidase and urate peroxidase activity, with measurable Michaelis-Menten parameters that reveal a particularly low Km for ascorbate as well as for urate - lower than the respective in vivo concentrations of these antioxidants in blood. Also, direct detection of a hemoglobin-ascorbate interaction was possible by monitoring the 1H-NMR spectrum of ascorbate in the presence of hemoglobin. The relative difference in structures between ascorbate and urate may raise the question as to exactly what the defining structural features would be, for a substrate that binds to hemoglobin with high affinity. Reported here are Michaelis-Menten parameters for hemoglobin acting as peroxidase against a number of other substrates of varying structures - gallate, caffeate, rutin, 3-hydroxyflavone, 3,6-dihydroxyflavone, quercetin, epicatechin, luteolin - all with high affinities (some higher than those of physiologically-relevant redox partners of Hb - ascorbate and urate). Moreover, this high affinity appears general to animal hemoglobins. 1 H-NMR and 13 C-NMR spectra reveal a general pattern wherein small hydrophilic antioxidants appear to all have their signals affected, presumably due to binding to hemoglobin. Fluorescence and calorimetry measurements confirm these conclusions. Docking calculations confirm the existence of binding sites on hemoglobin and on myoglobin for ascorbate as well as for other antioxidants. Support is found for involvement of Tyr42 in binding of three out of the four substrates investigated in the case of hemoglobin (including ascorbate and urate, as blood-contained relevant substrates), but also for Tyr145 (with urate and caffeate) and Tyr35 (with gallate). Copyright © 2018 Elsevier Inc. All rights reserved.

Report About the NASA-MSU Professional Enhancement Awards in 2015

NASA Technical Reports Server (NTRS)

Liu, Jianguo (Jack); Gutman, George

2015-01-01

With support from NASA and Michigan State University (MSU), 17 "NASA-MSU Professional Enhancement Award" recipients were able to attend the 2015 World Congress of Landscape Ecology. This year's conference was held in Portland (Oregon) during July 5-10, 2015 (http://www.ialeworldcongress.org/). On May 6, a dinner gathering was organized for the new NASA-MSU Award recipients. At the gathering, the participants first made a brief self-introduction regarding their background and research interests. Then they formed five groups to work on manuscripts. Furthermore, each new awardee was recognized with a certificate at the conference luncheon on July 6. In addition, the awardees attended a "Student/Mentor Lunch" on July 8 when the awardees (and other students) met with leading scientists. The awardees also attended a workshop on telecoupling on July 5. The awardees had a great time and were very productive at the conference, and many are continuing to collaborate on preparing manuscripts after the conference and preparing presentations for next year's meeting of US-IALE.

Multiple GISS AGCM Hindcasts and MSU Versions of 1979-1998

NASA Technical Reports Server (NTRS)

Shah, Kathryn Pierce; Rind, David; Druyan, Leonard; Lonergan, Patrick; Chandler, Mark

1998-01-01

Multiple realizations of the 1979-1998 time period have been simulated by the Goddard Institute for Space Studies Atmospheric General Circulation Model (GISS AGCM) to explore its responsiveness to accumulated forcings, particularly over sensitive agricultural regions. A microwave radiative transfer postprocessor has produced the AGCM's lower tropospheric, tropospheric and lower stratospheric brightness temperature (Tb) time series for correlations with the various Microwave Sounding Unit (MSU) time series available. MSU maps of monthly means and anomalies were also used to assess the AGCM's mean annual cycle and regional variability. Seven realizations by the AGCM were forced by observed sea surface temperatures (sst) through 1992 to gather rough standard deviations associated with internal model variability. Subsequent runs hindcast January 1979 through April 1998 with an accumulation of forcings: observed ssts, greenhouse gases, stratospheric volcanic aerosols. stratospheric and tropospheric ozone and tropospheric sulfate and black carbon aerosols. The goal of narrowing gaps between AGCM and MSU time series was complicated by MSU time series, by Tb simulation concerns and by unforced climatic variability in the AGCM and in the real world. Lower stratospheric Tb correlations between the AGCM and MSU for 1979-1998 reached as high as 0.91 +/-0.16 globally with sst, greenhouse gases, volcanic aerosol, stratospheric ozone forcings and tropospheric aerosols. Mid-tropospheric Tb correlations reached as high as 0.66 +/-.04 globally and 0.84 +/-.02 in the tropics. Oceanic lower tropospheric Tb correlations similarly reached 0.61 +/-.06 globally and 0.79 +/-.02 in the tropics. Of the sensitive agricultural areas considered, Nordeste in northeastern Brazil was simulated best with mid-tropospheric Tb correlations up to 0.75 +/- .03. The two other agricultural regions, in Africa and in the northern mid-latitudes, suffered from higher levels of non-sst variability. Zimbabwe had a maximum mid-tropospheric correlation of 0.54 +/- 0.11 while the U.S. Cornbelt had only 0.25 +/- .10. Precipitation and surface temperature performance are also examined over these regions. Correlations of MSU and AGCM time series mostly improved with addition of explicit atmospheric forcings in zonal bands but not in agricultural regional bins each encompassing only six AGCM gridcells.

Application of JLab 12GeV helium refrigeration system for the FRIB accelerator at MSU

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganni, Venkatarao; Knudsen, Peter N.; Arenius, Dana M.

The planned approach to have a turnkey helium refrigeration system for the MSU-FRIB accelerator system, encompassing the design, fabrication, installation and commissioning of the 4.5-K refrigerator cold box(es), cold compression system, warm compression system, gas management, oil removal and utility/ancillary systems, was found to be cost prohibitive. Following JLab’s suggestion, MSU-FRIB accelerator management made a formal request to evaluate the applicability of the recently designed 12GeV JLab cryogenic system for this application. The following paper will outline the findings and the planned approach for the FRIB helium refrigeration system.

Red wine induced modulation of vascular function: separating the role of polyphenols, ethanol, and urates.

PubMed

Boban, Mladen; Modun, Darko; Music, Ivana; Vukovic, Jonatan; Brizic, Ivica; Salamunic, Ilza; Obad, Ante; Palada, Ivan; Dujic, Zeljko

2006-05-01

By using red wine (RW), dealcoholized red wine (DARW), polyphenols-stripped red wine (PSRW), ethanol-water solution (ET), and water (W), the role of wine polyphenols, ethanol, and urate on vascular function was examined in humans (n = 9 per beverage) and on isolated rat aortic rings (n = 9). Healthy males randomly consumed each beverage in a cross-over design. Plasma ethanol, catechin, and urate concentrations were measured before and 30, 60 and 120 minutes after beverage intake. Endothelial function was assessed before and 60 minutes after beverage consumption by normalized flow-mediated dilation (FMD). RW and DARW induced similar vasodilatation in the isolated vessels whereas PSRW, ET, and W did not. All ethanol-containing beverages induced similar basal vasodilatation of brachial artery. Only intake of RW resulted in enhancement of endothelial response, despite similar plasma catechin concentration after DARW. The borderline effect of RW on FMD (P = 0.0531) became significant after FMD normalization (P = 0.0043) that neutralized blunting effect of ethanol-induced basal vasodilatation. Effects of PSRW and ET did not differ although plasma urate increased after PSRW and not after ET, indicating lack of urate influence on endothelial response. Acute vascular effects of RW, mediated by polyphenols, cannot be predicted by plasma catechin concentration only.

Reactive oxygen species promote tubular injury in diabetic nephropathy: The role of the mitochondrial ros-txnip-nlrp3 biological axis.

PubMed

Han, Yachun; Xu, Xiaoxuan; Tang, Chengyuan; Gao, Peng; Chen, Xianghui; Xiong, Xiaofen; Yang, Ming; Yang, Shikun; Zhu, Xuejing; Yuan, Shuguang; Liu, Fuyou; Xiao, Li; Kanwar, Yashpal S; Sun, Lin

2018-06-01

NLRP3/IL-1β activation via thioredoxin (TRX)/thioredoxin-interacting protein (TXNIP) following mitochondria ROS (mtROS) overproduction plays a key role in inflammation. However, the involvement of this process in tubular damage in the kidneys of patients with diabetic nephropathy (DN) is unclear. Here, we demonstrated that mtROS overproduction is accompanied by decreases in TRX expression and TXNIP up-regulation. In addition, we discovered that mtROS overproduction is also associated with increases in NLRP3/IL-1β and TGF-β expression in the kidneys of patients with DN and db/db mice. We reversed these changes in db/db mice by administering a peritoneal injection of MitoQ, an antioxidant targeting mtROS. Similar results were observed in human tubular HK-2 cells subjected to high-glucose (HG) conditions and treated with MitoQ. Treating HK-2 cells with MitoQ suppressed the dissociation of TRX from TXNIP and subsequently blocked the interaction between TXNIP and NLRP3, leading to the inhibition of NLRP3 inflammasome activation and IL-1β maturation. The effects of MitoQ were enhanced by pretreatment with TXNIP siRNA and abolished by pretreatment with monosodium urate (MSU) and TRX siRNA in vitro. These results suggest that mitochondrial ROS-TXNIP/NLRP3/IL-1β axis activation is responsible for tubular oxidative injury, which can be ameliorated by MitoQ via the inhibition of mtROS overproduction. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Release of the antioxidants ascorbate and urate from a nitrergically-innervated smooth muscle.

PubMed

Lilley, E; Gibson, A

1997-12-01

1. The main object of the present study was to determine whether ascorbate, an antioxidant which has been shown to protect nitric oxide (NO) from attack by scavenger molecules, might be released from nitrergically-innervated smooth muscle; ascorbate release from the rat anococcygeus was measured by use of h.p.l.c. with electrochemical detection. 2. Incubation of rat anococcygeus muscles in normal physiological salt solution (PSS; 30 min) resulted in release of ascorbate into the bathing medium (7.7 +/- 0.9 nmol g-1 tissue). This release was increased by 96% when muscles were incubated in high K+ (70 mM) PSS. The resting release of ascorbate was unaffected by tetrodotoxin (TTX; 1 microM), omega-conotoxin GVIA (10 nM) or omission of calcium ions from the PSS (with addition of 0.2 mM EGTA), but all three procedures attenuated the increased release observed under depolarizing conditions. Resting release of ascorbate was unaffected by glutamate (100 microM), aspartate (100 microM), gamma-aminobutyric acid (100 microM) or carbachol (50 microM). 3. A second h.p.l.c. peak, which always preceded the ascorbate peak, was identified as urate. Urate release from the anococcygeus, following 30 min incubation in normal PSS, was 64.6 +/- 12.7 nmol g-1 tissue but, unlike ascorbate, urate release was unchanged in high K+ PSS. In functional experiments, urate (100-400 microM) partially protected NO (15 microM)-induced relaxations of the rat anococcygeus from inhibition by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO; 50 microM), but not from inhibition by hydroquinone or duroquinone (both 100 microM). 4. Muscles chemically sympathectomized with 6-hydroxydopamine (6-OHDA, 500 microM; 2 h) still exhibited release of ascorbate (2.5 +/- 0.4 nmol g-1 tissue) and urate (22.2 +/- 2.9 nmol g-1 tissue); in both cases the release was similar to that observed in time-matched control tissues not exposed to 6-OHDA. High K+ PSS produced a TTX-sensitive increase in release of ascorbate, but not urate, from 6-OHDA-treated muscles. 5. The results demonstrate that significant amounts of ascorbate and urate are released from the rat anococcygeus muscle. Ascorbate, but not urate, release appears to be enhanced by activation of nerves which are resistant to 6-OHDA pretreatment. Since both antioxidants can protect NO from attack by scavenger molecules, their release in nitrergically-innervated tissues may be important for the provision of the correct redox environment to allow NO to fulfill its proposed neurotransmitter role.

Clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma.

PubMed

Kim, Tae-Min; An, Chang Hyeok; Rhee, Je-Keun; Jung, Seung-Hyun; Lee, Sung Hak; Baek, In-Pyo; Kim, Min Sung; Lee, Sug Hyung; Chung, Yeun-Jun

2015-09-29

Although the colorectal adenoma-to-carcinoma sequence represents a classical cancer progression model, the evolution of the mutational landscape underlying this model is not fully understood. In this study, we analyzed eight synchronous pairs of colorectal high-grade adenomas and carcinomas, four microsatellite-unstable (MSU) and four-stable (MSS) pairs, using whole-exome sequencing. In the MSU adenoma-carcinoma pairs, we observed no subclonal mutations in adenomas that became fixed in paired carcinomas, suggesting a 'parallel' evolution of synchronous adenoma-to-carcinoma, rather than a 'stepwise' evolution. The abundance of indel (in MSU and MSS pairs) and microsatellite instability (in MSU pairs) was noted in the later adenoma- or carcinoma-specific mutations, indicating that the mutational processes and functional constraints operative in early and late colorectal carcinogenesis are different. All MSU cases exhibited clonal, truncating mutations in ACVR2A, TGFBR2, and DNA mismatch repair genes, but none were present in APC or KRAS. In three MSS pairs, both APC and KRAS mutations were identified as both early and clonal events, often accompanying clonal copy number changes. An MSS case uniquely exhibited clonal ERBB2 amplification, followed by APC and TP53 mutations as carcinoma-specific events. Along with the previously unrecognized clonal origins of synchronous colorectal adenoma-carcinoma pairs, our study revealed that the preferred sequence of mutational events during colorectal carcinogenesis can be context-dependent.

Graduate Writing across the Disciplines, Introduction

ERIC Educational Resources Information Center

Brooks-Gillies, Marilee; Garcia, Elena G.; Kim, Soo Hyon; Manthey, Katie; Smith, Trixie

2015-01-01

While the editors of "Across the Disciplines" were working at the Michigan State University (MSU) Writing Center in 2011, they began focusing on the issues of graduate writing support through their involvement with the graduate writing groups hosted through the MSU Writing Center, conducting research on the benefits of such groups. When…

[The hyperiricosuria as an indicator of derangement of biologic functions of endoecology and adaptation, biologic reactions of excretion, inflammation and arterial tension].

PubMed

Titov, V N; Oshchepkova, E V; Dmitriev, V A; Gushchina, O V; Shiriaeva, Iu K; Iashin, A Ia

2012-04-01

During millions years in all animals allantoine (oxidized by uricase uric acid) was catabolite of purines and ascorbic acid was an acceptor of active forms of oxygen. The proximal tubules of nephron reabsorbed the trace amounts of uric acid Then during phylogenesis the primates had a mutation of ascorbic acid gen minus. Later on occurred a second spontaneous mutation and uricase gen minus and uric acid became catabolites of purines. In absence of ascorbic acid synthesis ions of urates became a major capturers of active forms of oxygen and all uric acid as before underwent the reabsorption. Later the carriers were formed which began in epithelium of proximal tubules to secrete all uric acid into urine. At every incident of "littering" of intercellular medium with endogenic flogogens (impairment of biologic function of endoecology) under compensatory development of biologic reaction of inflammation the need in inactivation of active forms of oxygen increases. Hence later on in phylogenesis one more stage was formed--post secretory reabsorption of uric acid In the biologic reaction of inflammation epithelium of proximal tubules initiates retentional hyperiricosuria. The general antioxidant activity of human blood plasma in 60% is presented by urates' ions. The excretion of uric acid includes 4 stages: filtration, full reabsorption, secretion and post secretory reabsorption. In phylogenesis these stages formed in sequence. The mild hyperiricosuria is most frequently considered as a non-specific indicator of activation of biologic reaction of inflammation. The productive hyperiricosuria develops more infrequently under surplus of meat food and cytolysis syndrome (intensification of cell loss in vivo). Under concentration of uric acid more than 400 mkmol/l part of urates circulates in intercellular medium in the form of crystals. The microcrystals of uric acid (biologic "litter") initiate the syndrome of systemic inflammatory response as an endogenic flogogen--initiator of inflammation. The uric acid in the form of ion-capturers of active forms of oxygen is involved into in the formation of syndrome of compensatory anti-inflammatory defense. It may be assumed that simultaneously with post-secretory reabsorption of ions of urates in proximal tubules of nephron occurs intensification of philogenetically late post-secretory reabsorption of ions of sodium and activation of of biologic reaction of hydrodynamic and hydraulic pressure in local pool of intravascular medium i.e. arterial tension. The uric acid simultaneously participates in realization of biologic function of endoecology and adaptation, biologic reactions of excretion, inflammation and arterial tension.

Factors influencing medication adherence in patients with gout: A descriptive correlational study.

PubMed

Chua, Xin Hui Jasmine; Lim, Siriwan; Lim, Fui Ping; Lim, Yee Nah Anita; He, Hong-Gu; Teng, Gim Gee

2018-01-01

To examine the factors influencing adherence to urate-lowering therapy in patients with gout in Singapore. Gout is the most common type of chronic inflammatory arthritis. Urate-lowering therapy is used to treat gout by reducing serum uric acid levels. However, adherence to urate-lowering therapy among patients remains poor. To date, there have been no available studies based on a conceptual framework that examined factors influencing medication adherence in patients with gout. Cross-sectional, descriptive correlational study. A convenience sample of outpatients (n = 108) was recruited between October 2014-January 2015 from a tertiary hospital in Singapore. Outcomes were measured by relevant valid and reliable instruments. Descriptive statistics and parametric tests including multiple linear regression were used to analyse the data. Although 44.4% of the participants were high adherers to urate-lowering therapy, the mean adherence level was moderate. Significant differences in medication adherence scores were found among the subgroups of gender, ethnicity, marital status, employment status and presence of comorbidity. Medication adherence was positively significantly correlated with age, number of comorbidities and beliefs about medicines. Linear regression showed that higher level of beliefs about medicines, presence of comorbidity and being married were factors positively influencing medication adherence. This study revealed moderate adherence to urate-lowering therapy in patients with gout in Singapore, indicating the need for strategies to improve adherence by considering its main influencing factors. Future research should be conducted to develop interventions targeted at modifying patients' beliefs about medicines in order to improve medication adherence. Findings from this study allow healthcare providers to quickly and easily identify patients who may have low adherence. Nurses should take the lead in educating patients on the mechanism of urate-lowering therapy and highlight the importance of adhering to it. © 2017 John Wiley & Sons Ltd.

Serum urate gene associations with incident gout, measured in the Framingham Heart Study, are modified by renal disease and not by body mass index.

PubMed

Reynolds, Richard J; Vazquez, Ana I; Srinivasasainagendra, Vinodh; Klimentidis, Yann C; Bridges, S Louis; Allison, David B; Singh, Jasvinder A

2016-02-01

We hypothesized that serum urate-associated SNPs, individually or collectively, interact with BMI and renal disease to contribute to risk of incident gout. We measured the incidence of gout and associated comorbidities using the original and offspring cohorts of the Framingham Heart Study. We used direct and imputed genotypes for eight validated serum urate loci. We fit binomial regression models of gout incidence as a function of the covariates, age, type 2 diabetes, sex, and all main and interaction effects of the eight serum urate SNPs with BMI and renal disease. Models were also fit with a genetic risk score for serum urate levels which corresponds to the sum of risk alleles at the eight SNPs. Model covariates, age (P = 5.95E-06), sex (P = 2.46E-39), diabetes (P = 2.34E-07), BMI (P = 1.14E-11) and the SNPs, rs1967017 (P = 9.54E-03), rs13129697 (P = 4.34E-07), rs2199936 (P = 7.28E-03) and rs675209 (P = 4.84E-02) were all associated with incident gout. No BMI by SNP or BMI by serum urate genetic risk score interactions were statistically significant, but renal disease by rs1106766 was statistically significant (P = 6.12E-03). We demonstrated that minor alleles of rs1106766 (intergenic, INHBC) were negatively associated with the risk of incident gout in subjects without renal disease, but not for individuals with renal disease. These analyses demonstrate that a significant component of the risk of gout may involve complex interplay between genes and environment.

Serum urate gene associations with incident gout, measured in the Framingham Heart Study, are modified by renal disease and not by body mass index

PubMed Central

Reynolds, Richard J.; Vazquez, Ana I.; Srinivasasainagendra, Vinodh; Klimentidis, Yann C.; Bridges, S. Louis; Allison, David B.; Singh, Jasvinder A.

2015-01-01

Introduction/objectives We hypothesized that serum urate-associated SNPs, individually or collectively, interact with BMI and renal disease to contribute to risk for incident gout. Method We measured the incidence of gout and associated comorbidities using the Original and Offspring cohorts of the Framingham Heart Study. We used direct and imputed genotypes for eight validated serum urate loci. We fit binomial regression models of gout incidence as a function of the covariates, age, type 2 diabetes, sex, and all main and interaction effects of the eight serum urate SNPs with BMI and renal disease. Models were also fit with a genetic risk score for serum urate levels which corresponds to the sum of risk alleles at the 8 SNPs. Results Model covariates, age (P = 5.95E-06), sex (P = 2.46E-39), diabetes (P = 2.34E-07), BMI (P = 1.14E-11) and the SNPs, rs1967017 (P = 9.54E-03), rs13129697 (P = 4.34E-07), rs2199936 (P = 7.28E-03) and rs675209 (P = 4.84E-02) were all associated with incident gout. No BMI by SNP or BMI by serum urate genetic risk score (GRS) interactions were statistically significant, but renal disease by rs1106766 was statistically significant (P=6.12E-03). Conclusions We demonstrated that minor alleles of rs1106766 (intergenic, INHBC) were negatively associated with the risk of incident gout in subjects without renal disease, but not for individuals with renal disease. These analyses demonstrate that a significant component of the risk for gout may involve complex interplay between genes and environment. PMID:26427508

VizieR Online Data Catalog: URAT Parallax Catalog (UPC) (Finch+, 2016)

NASA Astrophysics Data System (ADS)

Finch, C. T.; Zacharias, N.

2016-04-01

The URAT Parallax Catalog (UPC) consists of 112177 parallaxes. The catalog utilizes all Northern Hemisphere epoch data from the United States Naval Observatory (USNO) Robotic Astrometric Telescope (URAT). This data includes all individual exposures from April 2012 to June 2015 giving a larger epoch baseline for determining parallaxes over the 2-year span of the First USNO Robotic Astrometric Telescope Catalog (URAT1) (Zacharias et al., 2015, Cat. I/329) published data. The URAT parallax pipeline is custom code that utilizes routines from (Jao, C.-W., 2004, PhD thesis Georgia Stat), the JPL DE405 ephemeris and Green's parallax factor (Green, R.M., 1985, Spherical Astronomy) for determining parallaxes from a weighted least-squares reduction. The relative parallaxes have been corrected to absolute by using the distance color relation described in (Finch et. al, 2014, Cat. J/AJ/148/119) to determine a mean distance of all UCAC4 reference stars (R=8-16 mag) used in the astrometric reductions. Presented here are all significant parallaxes from the URAT Northern Hemisphere epoch data comprising of 2 groups: a) URAT parallax results for stars with prior published parallax, and b) first time trigonometric parallaxes as obtained from URAT data of stars without prior published parallax. Note, more stringent selection criteria have been applied to the second group than the first in order to keep the rate of false detections low. For specific information about the astrometric reductions please see 'The First U.S. Naval Observatory Robotic Astrometric Telescope Catalog' published paper (Zacharias et al., 2015AJ....150..101Z, Cat. I/329). For complete details regarding the parallax pipeline please see 'Parallax Results From URAT Epoch Data' (Finch and Zacharias, 2016, AJ, in press). This catalog gives all positions on the ICRS at Epoch J2014.0; it covers the magnitude range 6.56 to 16.93 in the URAT band-pass, with an average parallax precision of 4.3mas for stars having no known parallax and 10.8mas for stars matched to external parallax sources. This catalog covers the sky from about North of -12.75° declination. This catalog was matched with the Hipparcos catalog, Yale Parallax Catalog, (Finch & Zacharias, 2016, AJ, in press), MEarth (Dittmann et. al., 2014ApJ...784..156D) and the SIMBAD database to obtain known parallax and star names. For stars matched to SIMBAD using the automated search feature, only the parallaxes are given so no information on the parallax errors or source for the parallax are reported for those stars in this catalog. A flag is included to show which catalog or database the URAT parallax was matched with. Only the data from the first catalog that was matched is reported here according to the following priority list. This means for example, if a star was matched with Hipparcos, that information was used while possible other catalog data are not listed here. -------------------------------------------------------- # stars flg catalog -------------------------------------------------------- 53500 0 no catalog match 55549 1 Hipparcos 254 2 Yale Parallax Catalog 1041 3 Finch and Zacharias 2016 (UPM NNNN-NNNN) 1431 4 MEarth parallaxes 402 5 SIMBAD Database (w/parallax) -------------------------------------------------------- 112177 total number stars in catalog -------------------------------------------------------- Not all parallaxes from the URAT epoch data are included in this catalog. Only those data meeting the following criteria have been included. For the epoch data we only used data having a FWHM<=7.0pixel; amplitude between 500 and 30000ADU; sigma x,y <=90.0mas; number of observations >=20 and epoch span>=1.0 years. The limits imposed on individual image amplitude, image profile width (FWHM) and position fit errors (sigma) are set to not allow saturated stars, stars with too few photons or poorly determined positions to be used in the parallax solution. We present all URAT parallax solutions having a known parallax from an external data source regardless of the quality of the solution (srcflg=1-5). This was done for the user to better understand the limitations for determining parallaxes with the current URAT epoch data. For the remaining URAT parallaxes without a match to any published trigonometric parallax (srcflg=0) we only present a parallax solutions having: 1) a parallax error <=10mas 2) a parallax error <=1/4 the relative parallax 3) epoch span >=1.5 years 4) number of observations used >=30 5) fit sigma<=1.4 (unit weight) 6) average image elongation <1.1. All of these cuts have been implemented in an attempt to lower the number of possible erroneous parallax solutions entering our catalog. However, the URAT reduction process does not take provisions for close doubles (blended images) of arcsecond-level separations. Many of the parallaxes, particularly those with large mean elongation, large parallax error, large fit sigma and many rejected observations are possibly blended images leading to a higher chance of an erroneous parallax solutions. A visual inspection of all residual plots and real sky images would not be practical for the entire catalog. However, we have included information in the catalog to help the user to determine if a solution should be investigated further. (1 data file).

The limitations of Gram-stain microscopy of synovial fluid in concomitant septic and crystal arthritis.

PubMed

Stirling, Paul; Tahir, Mohammed; Atkinson, Henry Dushan

2017-03-29

Rapid diagnosis of septic arthritis from Gram-stain microscopy is limited by an inherent false-negative rate of 25-78%. The presence of concomitant crystal arthritis in 5% of cases represents a particular diagnostic challenge. This study aims to investigate the effects that a concomitant crystal arthropathy have on the ability of Gram-stain microscopy of synovial fluid to diagnose a septic arthritis. This is a 12-year retrospective cohort study. Inclusion criteria were a positive synovial fluid culture result with a positive clinical diagnosis of septic arthritis. Results were correlated with presence or absence of urate and calcium pyrophosphate crystals, and Gram-stain result. During this time our collection and analysis methods remained unchanged. All samples were collected in Lithium Heparin containers. Chi-squared test with a p value < 0.05 was considered significant. 602 synovial fluid samples were included. 162 cases of concomitant crystal arthritis were identified (27%). Of these, 16 (10%) had an initial negative Gram-stain. Of the 440 samples with no crystals detected, 18 (4%) had an initial negative Gram-stain microscopy result (p < 0.05). The incidence of concurrent septic and crystal arthritis may be higher than previously thought. Synovial fluid samples in concomitant septic and crystal arthritis are significantly less likely to have a positive Gram-stain at microscopy than in cases of an isolated septic arthritis. We would advise the clinician to maintain a high index of suspicion for septic arthritis in these patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

VizieR Online Data Catalog: 1103 parallaxes and proper motions from URAT (Finch+, 2016)

NASA Astrophysics Data System (ADS)

Finch, C. T.; Zacharias, N.

2016-07-01

We present 1103 trigonometric parallaxes and proper motions from the United States Naval Observatory (USNO) Robotic Astrometric Telescope (URAT) observations taken at the Naval Observatory Flagstaff Station (NOFS). URAT observes through a single filter (part of the dewar window) to provide a fixed bandpass of about 680 to 760nm. The clear aperture of the USNO astrograph is 206mm with a focal length of only 2m. A single exposure covers 28 square degrees with a resolution of 0.9arcsec/pixel. Each of the four large CCDs in the focal plane covers a 2.65 by 2.65 deg area on the sky. Data of all three years of operations (2012 April to 2015 June) at the NOFS are used here for this parallax investigation. For more details about the project, instrument, and observing the reader is referred to the URAT1 paper (Zacharias et al. 2015, cat. I/329). (3 data files).

Unusual Dermatological Manifestations of Gout: Review of Literature and a Case Report

PubMed Central

Ortega, Viviana Gómez; Gaona, Jennifer; Motta, Adriana; Medina Barragán, Oskar Javier

2015-01-01

Background: Gouty panniculitis is a rare clinical manifestation of gout, characterized by deposits of monosodium urate crystals in the hypodermis. Our aim was to describe atypical and rare clinical presentations of gouty tophi. Methods: We searched relevant English and Spanish literature of unusual gout manifestations using the following keywords: giant, gout, panniculitis, gouty panniculitis, gouty tophi, rare manifestations of gout, gouty, tophi, tophus, monosodium urate, uric acid, and unusual. Well-described case reports, case series, and review articles were evaluated and included in the literature review. Results: International literature has reported fewer than 10 cases of gouty panniculitis worldwide. In this case report, the patient presents a rare manifestation of gouty panniculitis, with typical joint injuries, gouty tophi in both lower and upper extremities, chronic gouty tophi in the nose, for which only 3 cases have been reported in literature, and great hypertrophy of adipose tissue in the lower back. Conclusions: Tophi can be found in atypical locations, which increase morbidities and deformities caused by the disease. We report an interesting case of gouty panniculitis associated with great hypertrophy of the adipose tissue, a rare manifestation of gout, and unusual locations of tophi. These clinical manifestations in our patient have not been recorded before, which leads us to think that we are in the presence of a new dermatological manifestation of gout. PMID:26301134

Study of the QCD Phase Diagram using STAR at RHIC - Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Westfall, Gary

This grant supported the MSU STAR Group from April 1, 1998 to October 31, 2016. Originally the MSU STAR Group consisted of the principal investigator (PI), a staff physicist, and one graduate student. Funds were provided for half the summer salary of the PI, the full salary of the staff physicist, and half the costs associated with one graduate student. The other half of the PI’s summer salary and graduate student costs was covered by NSCL. In addition, this grant provided funds for travel and workstations related to STAR. Starting in 2009, the MSU STAR Group replaced the staff physicistmore » with a postdoctoral scientist.« less

Professional Education in Instructional Development at Michigan State University.

ERIC Educational Resources Information Center

Gustafson, Kent L.; Schuller, Charles F.

This chapter describes the history and philosophy of the professional preparation program for instructional developers at Michigan State University (MSU). The history of the program is traced from the establishment of the MSU Audiovisual Center in 1952 through the Joint Film Catalog and the NDEA (National Defense Education Act) Fellowships in the…

MSU-Test: A Tool for Measuring Students' Achievement

ERIC Educational Resources Information Center

Chansirisira, Pacharawit; Nuangchalerm, Prasart; Morakot, Nongnit; Khamkong, Surasak

2011-01-01

The study aims to employ MSU-test as a tool to measure Mahasarakham student in secondary and high school levels to achieve their learning potential. The importance of this study will help university understanding school potential and provide information to increase students' score. Two thousand and seven hundred eight nine students participated in…

Mobile surveillance units (MSU) for border protection and homeland defense

NASA Astrophysics Data System (ADS)

Crandon, Christopher; Kimber, Paul K.

2003-09-01

During the last 12 years the European Union (EU) has financed the new member applicant countries of Central and Eastern Europe in their preparation for joining the EU. Based on this enlargement of the EU, funding for border protection has been made available from the overall infrastructure improvement budget. Border protection was required in areas where border conflicts had taken place and to limit illegal immigration and smuggling. After 9/11 defence against terrorist activities will no doubt be added to the requirement. This paper describes the approach taken in the provision of police and para-military Mobile Surveillance Units (MSU's). This approach may also be considered for the US Homeland Defense initiative. These MSU's utilize standard road vehicles converted to use high performance military thermal imagers, such as SiGMA. In future the current, in service, MSU will require increased sensor integration and networking to cover land and coastal borders. The underlying key is affordability for the police and para-military markets while retaining the highest performance derived from the latest military standard thermal imagers.

Genetic variants in two pathways influence serum urate levels and gout risk: a systematic pathway analysis.

PubMed

Dong, Zheng; Zhou, Jingru; Xu, Xia; Jiang, Shuai; Li, Yuan; Zhao, Dongbao; Yang, Chengde; Ma, Yanyun; Wang, Yi; He, Hongjun; Ji, Hengdong; Zhang, Juan; Yuan, Ziyu; Yang, Yajun; Wang, Xiaofeng; Pang, Yafei; Jin, Li; Zou, Hejian; Wang, Jiucun

2018-03-01

The aims of this study were to identify candidate pathways associated with serum urate and to explore the genetic effect of those pathways on the risk of gout. Pathway analysis of the loci identified in genome-wide association studies (GWASs) showed that the ion transmembrane transporter activity pathway (GO: 0015075) and the secondary active transmembrane transporter activity pathway (GO: 0015291) were both associated with serum urate concentrations, with P FDR values of 0.004 and 0.007, respectively. In a Chinese population of 4,332 individuals, the two pathways were also found to be associated with serum urate (P FDR  = 1.88E-05 and 3.44E-04, separately). In addition, these two pathways were further associated with the pathogenesis of gout (P FDR  = 1.08E-08 and 2.66E-03, respectively) in the Chinese population and a novel gout-associated gene, SLC17A2, was identified (OR = 0.83, P FDR  = 0.017). The mRNA expression of candidate genes also showed significant differences among different groups at pathway level. The present study identified two transmembrane transporter activity pathways (GO: 0015075 and GO: 0015291) were associations with serum urate concentrations and the risk of gout. SLC17A2 was identified as a novel gene that influenced the risk of gout.

Previous Dosage of Allopurinol Is a Strong Determinant of Febuxostat Efficacy.

PubMed

Koide, Hiroyoshi; Hira, Daiki; Tsujimoto, Masayuki; Katsube, Yurie; Minegaki, Tetsuya; Uzu, Takashi; Ikeda, Yoshito; Morita, Shin-Ya; Nishiguchi, Kohshi; Terada, Tomohiro

2017-01-01

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. The data, including patient information and laboratory data, were collected from electronic medical records. Serum urate lowering effects of febuxostat were evaluated by calculating the change in serum urate level at baseline and at 8-12 weeks after starting febuxostat. The multiple regression analysis showed the change in serum urate level was significantly lower in male patients and in those with a lower baseline serum urate level, higher previous dose of allopurinol, lower dose of febuxostat and lower body surface area-unadjusted estimated glomerular filtration rate. Concomitantly administered drugs did not show a significantly influence on the efficacy of febuxostat. In conclusion, it should be noted that the serum urate lowering efficacy of febuxostat may decrease in patients with a higher previous dose of allopurinol, renal impairment or male patients. The basic findings of the present study are believed to contribute to the proper use of febuxostat.

Urate oxidase knockdown decreases oxidative stress in a murine hepatic cell line

USDA-ARS?s Scientific Manuscript database

Humans, birds, and some primates do not express the uric acid degrading enzyme urate oxidase (UOX) and, as a result, have plasma uric acid concentrations higher than UOX expressing animals. Although high uric acid concentrations are suggested to increase the antioxidant defense system and provide a...

Virtual Journal Room: MSU Libraries Table of Contents Service

ERIC Educational Resources Information Center

Sutherland, Michael; Clark, Jason

2009-01-01

Montana State University (MSU) Libraries (where the authors serve as web services librarian and digital initiatives librarian, respectively) is perhaps unique because it has no current periodicals room due to lack of space. As a result, finding current journals for research is difficult for its patrons, who do not always know how or where to…

Montclair State University: Documentation of the Teachers for a New Era Learning Network. Case Study

ERIC Educational Resources Information Center

Academy for Educational Development, 2009

2009-01-01

The Academy for Educational Development (AED) sent a research team to Montclair State University (MSU) on September 25-26, 2008 to conduct interviews with individuals who play important roles in the university's teacher preparation program. These interviews, along with additional documentation provided by MSU and identified by the AED research…

Are We There Yet?

ERIC Educational Resources Information Center

Rice, George; Bowman, Michael

2007-01-01

Children in the back seat on a long trip are not the only ones asking the question "Are we there yet?" At Murray State University (MSU) and other universities starting new programs, the question becomes one of validation of the program. In the late 90s, MSU, a midsize university, was entrusted with the responsibility of developing a program of…

The Effect of Individual Learning Styles on Student GPA in Engineering Education at Morgan State University

ERIC Educational Resources Information Center

Hargrove, S. Keith, Sr.; Wheatland, John A.; Ding, Duowen; Brown, Cordelia M.

2008-01-01

The Clarence M. Mitchell School of Engineering at Morgan State University (MSU) is one of nine historically Black colleges and universities with undergraduate engineering programs accredited by the Accreditation Board for Engineering and Technology (ABET). Since 2001, the School of Engineering at MSU has been a participant in a multi-school…

TEDS-M 2008 User Guide for the International Database

ERIC Educational Resources Information Center

Brese, Falk, Ed.

2012-01-01

The Teacher Education Study in Mathematics or TEDS-M is a study conducted under the aegis of the International Association for the Evaluation of Educational Achievement (IEA). The lead research center for the study is the International Study Center at Michigan State University (ISC/MSU). The ISC/MSU worked from 2006 to 2011 with the International…

Concentrating Solar Power Projects - Urat Middle Banner 100MW Thermal Oil

Science.gov Websites

Parabolic Trough project | Concentrating Solar Power | NREL Middle Banner 100MW Thermal Oil Thermal Oil Parabolic Trough project Country: China Location: Urat Middle Banner (Inner Mongolia) Owner(s , 2017 Start Production: 2018 Participants Developer(s): Changzhou Royal Tech Solar Thermal Equipment Co

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ames, B.N.; Cathcart, R.; Schwiers, E.

During primate evolution, a major factor in lengthening life-span and decreasing age-specific cancer rates may have been improved protective mechanisms against oxygen radicals. We propose that one of these protective systems is plasma uric acid, the level of which increased markedly during primate evolution as a consequence of a series of mutations. Uric acid is a powerful antioxidant and is a scavenger of singlet oxygen and radicals. We show that, at physiological concentrations, urate reduces the oxo-heme oxidant formed by peroxide reaction with hemoglobin, protects erythrocyte ghosts against lipid peroxidation, and protects erythrocytes from peroxidative damage leading to lysis. Uratemore » is about as effective an antioxidant as ascorbate in these experiments. Urate is much more easily oxidized than deoxynucleosides by singlet oxygen and is destroyed by hydroxyl radicals at a comparable rate. The plasma urate level in humans (about 300 ..mu..M) is considerably higher than the ascorbate level, making it one of the major antioxidants in humans. Previous work on urate reported in the literature supports our experiments and interpretations, although the findings were not discussed in a physiological context.« less

The Effects of Modified Simiao Decoction in the Treatment of Gouty Arthritis: A Systematic Review and Meta-Analysis

PubMed Central

Huang, Ying; Wen, Cai-Yu-Zhu; Zhang, Jun-Jun; Xing, Guo-Lan; Chen, Zhe

2017-01-01

The modified Simiao decoctions (MSD) have been wildly applied in the treatment of gouty arthritis in China. However, the evidence needs to be evaluated by a systematic review and meta-analysis. After filtering, twenty-four randomised, controlled trials (RCTs) comparing the effects of MSD and anti-inflammation medications and/or urate-lowering therapies in patients with gouty arthritis were included. In comparison with anti-inflammation medications, urate-lowering therapies, or coadministration of anti-inflammation medications and urate-lowering therapies, MSD monotherapy significantly lowered serum uric acid (p < 0.00001, mean difference = −90.62, and 95% CI [−128.38, −52.86]; p < 0.00001, mean difference = −91.43, and 95% CI [−122.38, −60.49]; p = 0.02, mean difference = −40.30, and 95% CI [−74.24, −6.36], resp.). Compared with anti-inflammation medications and/or urate-lowering therapies, MSD monotherapy significantly decreased ESR (p < 0.00001; mean difference = −8.11; 95% CI [−12.53, −3.69]) and CRP (p = 0.03; mean difference = −3.21; 95% CI [−6.07, −0.36]). Additionally, the adverse effects (AEs) of MSD were fewer (p < 0.00001; OR = 0.08; 95% CI [0.05, 0.16]). MSD are effective in the treatment of gouty arthritis through anti-inflammation and lowering urate. However, the efficacy of MSD should be estimated with more RCTs. PMID:28373889

Interpretation of Brain CT Scans in the Field by Critical Care Physicians in a Mobile Stroke Unit

PubMed Central

Zakariassen, Erik; Lindner, Thomas; Nome, Terje; Bache, Kristi G.; Røislien, Jo; Gleditsch, Jostein; Solyga, Volker; Russell, David; Lund, Christian G.

2017-01-01

ABSTRACT BACKGROUND AND PURPOSE In acute stroke, thromboembolism or spontaneous hemorrhage abruptly reduces blood flow to a part of the brain. To limit necrosis, rapid radiological identification of the pathological mechanism must be conducted to allow the initiation of targeted treatment. The aim of the Norwegian Acute Stroke Prehospital Project is to determine if anesthesiologists, trained in prehospital critical care, may accurately assess cerebral computed tomography (CT) scans in a mobile stroke unit (MSU). METHODS In this pilot study, 13 anesthesiologists assessed unselected acute stroke patients with a cerebral CT scan in an MSU. The scans were simultaneously available by teleradiology at the receiving hospital and the on‐call radiologist. CT scan interpretation was focused on the radiological diagnosis of acute stroke and contraindications for thrombolysis. The aim of this study was to find inter‐rater agreement between the pre‐ and in‐hospital radiological assessments. A neuroradiologist evaluated all CT scans retrospectively. Statistical analysis of inter‐rater agreement was analyzed with Cohen's kappa. RESULTS Fifty‐one cerebral CT scans from the MSU were included. Inter‐rater agreement between prehospital anesthesiologists and the in‐hospital on‐call radiologists was excellent in finding radiological selection for thrombolysis (kappa .87). Prehospital CT scans were conducted in median 10 minutes (7 and 14 minutes) in the MSU, and median 39 minutes (31 and 48 minutes) before arrival at the receiving hospital. CONCLUSION This pilot study shows that anesthesiologists trained in prehospital critical care may effectively assess cerebral CT scans in an MSU, and determine if there are radiological contraindications for thrombolysis. PMID:28766306

Global Warming Estimation from MSU

NASA Technical Reports Server (NTRS)

Prabhakara, C.; Iacovazzi, Robert; Yoo, Jung-Moon

1998-01-01

Microwave Sounding Unit (MSU) radiometer observations in Ch 2 (53.74 GHz) from sequential, sun-synchronous, polar-orbiting NOAA satellites contain small systematic errors. Some of these errors are time-dependent and some are time-independent. Small errors in Ch 2 data of successive satellites arise from calibration differences. Also, successive NOAA satellites tend to have different Local Equatorial Crossing Times (LECT), which introduce differences in Ch 2 data due to the diurnal cycle. These two sources of systematic error are largely time independent. However, because of atmospheric drag, there can be a drift in the LECT of a given satellite, which introduces time-dependent systematic errors. One of these errors is due to the progressive chance in the diurnal cycle and the other is due to associated chances in instrument heating by the sun. In order to infer global temperature trend from the these MSU data, we have eliminated explicitly the time-independent systematic errors. Both of the time-dependent errors cannot be assessed from each satellite. For this reason, their cumulative effect on the global temperature trend is evaluated implicitly. Christy et al. (1998) (CSL). based on their method of analysis of the MSU Ch 2 data, infer a global temperature cooling trend (-0.046 K per decade) from 1979 to 1997, although their near nadir measurements yield near zero trend (0.003 K/decade). Utilising an independent method of analysis, we infer global temperature warmed by 0.12 +/- 0.06 C per decade from the observations of the MSU Ch 2 during the period 1980 to 1997.

PecS regulates the urate-responsive expression of type 1 fimbriae in Klebsiella pneumoniae CG43.

PubMed

Wang, Zhe-Chong; Liu, Chia-Jui; Huang, Ying-Jung; Wang, Yu-Seng; Peng, Hwei-Ling

2015-12-01

In the Klebsiella pneumoniae CG43 genome, the divergently transcribed genes coding for PecS, the MarR-type transcription factor, and PecM, the drug metabolite transporter, are located between the type 1 and type 3 fimbrial gene clusters. The intergenic sequence pecO between pecS and pecM contains three putative PecS binding sites and a CpxR box. Electrophoretic mobility shift assay revealed that the recombinant PecS and CpxR could specifically bind to the pecO sequence, and the specific interaction of PecS and pecO could be attenuated by urate. The expression of pecS and pecM was negatively regulated by CpxAR and PecS, and was inducible by exogenous urate in the absence of cpxAR. Compared with CG43S3ΔcpxAR, the derived mutants CG43S3ΔcpxARΔpecS and CG43S3ΔcpxARΔpecSΔpecM exerted similar levels of sensitivity to H2O2 or paraquat, but higher levels of mannose-sensitive yeast agglutination activity and FimA production. The promoter activity and transcript levels of fimA in CG43S3ΔcpxAR were also increased by deleting pecS. However, no binding activity between PecS and the fimA promoter could be observed. Nevertheless, PecS deletion could reduce the expression of the global regulator HNS and release the negative effect of HNS on FimA expression. In CG43S3ΔcpxAR, the expression of FimA as well as PecS was inducible by urate, whilst urate-induced FimA expression was inhibited by the deletion of pecS. Taken together, we propose that K. pneumoniae PecS indirectly and negatively regulates the expression of type 1 fimbriae, and the regulation is urate-inducible in the absence of CpxAR.

Urinary and plasma oxalate during ingestion of pure ascorbic acid: a re-evaluation.

PubMed

Fituri, N; Allawi, N; Bentley, M; Costello, J

1983-01-01

Daily ingestion of 8 g of pure ascorbic acid by 8 normal subjects for 7 days did not, in contrast to previous reports in the literature, significantly alter urinary or plasma oxalate during or after ingestion. When urine with raised ascorbate values was heated at 100 degrees C for 30 min, a significant increase in urinary oxalate concentration was observed. Plasma ascorbate reached a mean value during ingestion of 3.3 mg/100 ml. Urinary citrate excretion significantly decreased during the first 4 days of ascorbic acid ingestion; however, the urinary inhibitory activity of calcium oxalate crystal growth was not significantly altered. Urinary and serum urate as well as urinary calcium and magnesium were unaltered by ingestion of the vitamin supplement.

[Chronic tophaceous gout].

PubMed

González-Rozas, M; Prieto de Paula, J M; Franco Hidalgo, S; López Pedreira, M R

2013-09-01

Gout is a common illness, usually of unknown etiology, is more frequent in men, and with a prevalence that increases with age. It is characterized by recurrent episodes of acute arthritis due to the deposition of monosodium urate crystals in joints. The underlying disorder in most cases is hyperuricemia, usually as a consequence of impairment in its renal excretion. Although it is generally believed that both the diagnosis and treatment are simple, the truth is that the level of adherence of clinical decisions using the existing guidelines is poor. We describe a case of chronic tophaceous gout, and review the general characteristics of this condition. Copyright © 2011 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

The US Forest Service Insect Unit in East Lansing, MI, turns 50

Treesearch

Robert A. Haack

2006-01-01

There has been a USDA Forest Service Insect Unit located on the Michigan State University (MSU) campus in East Lansing, MI, since March 1956. Over the years, MSU has provided strong support for the Insect Unit, including both office and laboratory space through the Departments of Entomology and Forestry. The Unit's scientists have usually served as adjunct faculty...

Generation of a mesoporous silica MSU shell onto solid core silica nanoparticles using a simple two-step sol-gel process.

PubMed

Allouche, Joachim; Dupin, Jean-Charles; Gonbeau, Danielle

2011-07-14

Silica core-shell nanoparticles with a MSU shell have been synthesized using several non-ionic poly(ethylene oxide) based surfactants via a two step sol-gel method. The materials exhibit a typical worm-hole pore structure and tunable pore diameters between 2.4 nm and 5.8 nm.

Aligning Academic Offerings with Industry Needs and Facility Construction, While Making Space for Relevant Public Private Partnerships (P3s)

ERIC Educational Resources Information Center

Golich, Vicki L.; Haynes, Sandra; Hillhouse, Erin; Pfeifer, David

2018-01-01

Metropolitan State University of Denver (MSU Denver) has been educating students for Colorado's urban workforce for over fifty years. The following case study of MSU Denver's new Aerospace Engineering Sciences (AES) Building reveals the roles played by partnerships among universities, faculty, and local civic and industry leaders in creating new…

Interannual variability of the annual cycle of temperature channel-2 msu data over northern hemisphere

NASA Astrophysics Data System (ADS)

Tesouro, M.; Gimeno, L.; de La Torre, L.; Nieto, R.; Añel, J. A.; Ribera, P.; García, R.; Hernández, E.

2003-04-01

The seasonal cycle of the temperature MSU data in the Northern Hemisphere was investigated with the aim of studing interannual variability. Data consist of daily temperatures from the MSU-channel 2 that represent the lower troposphere. The analyzed area was the whole Northern Hemisphere and the studied period the last 23 years. Daily data were adjusted to the following expression for each year: y=a+b*sin(((2*PI)/d)x+c) The amplitude of the wave and the first inflexion point were used as indicators of the seasonal cycle. Results show a positive correlation in high latitudes between the NAO index and the amplitude and a negative one in middle latitudes. Correlations between the NAO index and the first inflexion point were negative for high latitudes regions.

Study for Updated Gout Classification Criteria (SUGAR): identification of features to classify gout

PubMed Central

Taylor, William J.; Fransen, Jaap; Jansen, Tim L.; Dalbeth, Nicola; Schumacher, H. Ralph; Brown, Melanie; Louthrenoo, Worawit; Vazquez-Mellado, Janitzia; Eliseev, Maxim; McCarthy, Geraldine; Stamp, Lisa K.; Perez-Ruiz, Fernando; Sivera, Francisca; Ea, Hang-Korng; Gerritsen, Martijn; Scire, Carlo; Cavagna, Lorenzo; Lin, Chingtsai; Chou, Yin-Yi; Tausche, Anne-Kathrin; Vargas-Santos, Ana Beatriz; Janssen, Matthijs; Chen, Jiunn-Horng; Slot, Ole; Cimmino, Marco A.; Uhlig, Till; Neogi, Tuhina

2015-01-01

Objective To determine which clinical, laboratory and imaging features most accurately distinguished gout from non-gout. Methods A cross-sectional study of consecutive rheumatology clinic patients with at least one swollen joint or subcutaneous tophus. Gout was defined by synovial fluid or tophus aspirate microscopy by certified examiners in all patients. The sample was randomly divided into a model development (2/3) and test sample (1/3). Univariate and multivariate association between clinical features and MSU-defined gout was determined using logistic regression modelling. Shrinkage of regression weights was performed to prevent over-fitting of the final model. Latent class analysis was conducted to identify patterns of joint involvement. Results In total, 983 patients were included. Gout was present in 509 (52%). In the development sample (n=653), these features were selected for the final model (multivariate OR) joint erythema (2.13), difficulty walking (7.34), time to maximal pain < 24 hours (1.32), resolution by 2 weeks (3.58), tophus (7.29), MTP1 ever involved (2.30), location of currently tender joints: Other foot/ankle (2.28), MTP1 (2.82), serum urate level > 6 mg/dl (0.36 mmol/l) (3.35), ultrasound double contour sign (7.23), Xray erosion or cyst (2.49). The final model performed adequately in the test set with no evidence of misfit, high discrimination and predictive ability. MTP1 involvement was the most common joint pattern (39.4%) in gout cases. Conclusion Ten key discriminating features have been identified for further evaluation for new gout classification criteria. Ultrasound findings and degree of uricemia add discriminating value, and will significantly contribute to more accurate classification criteria. PMID:25777045

[Effects of electro-acupuncture on expression of triggering receptor expressed on myeloid cells 1 in ankle joint synovial tissue of acute gouty arthritis rats].

PubMed

Zhang, Chao-Nan; Huang, Xue-Kuan; Luo, Yan; Jiang, Juan; Wan, Lei; Wang, Ling

2015-01-01

To investigate the effects of electro-acupuncture (EA) on the expression of triggering receptor expressed on myeloid cell (TREM)l in ankle joint synovial tissue of acute gouty arthritis (AGA) rats. Forty male SD rats were randomly divided into 4 groups: normal, AGA, medication and EA group, 10 rats in each group. AGA model was established by induced monosodium urate (MSU) method, except the normal group. Tow days before AGA model was established, normal and AGA groups were lavaged with normal saline (20 ml/kg), medication group was lavaged with colchicine solution (20 ml/kg), EA(1.5-2 Hz, D.-D.wave, 9v; 1-3 rnA) was applied to "Sanyinjiao" (SP6), "jiexi" (ST41) and "Kunlun" (BL60) for 20 min, once daily;continuously for 9 days. Then observed the changes in dysfunction, and the content of TNF-α and IL-lβ detected by ELISA, the expression of TREM-l detected by immunohistochemistry and western blot. Compared to the normal group, the AGA group of the dysfunction index increased significantly (P<0.01), the content of TNF-α and IL-lβ increased significantly (P<0.05), the expression of TREM-l in synovial tissue increased significantly (P<0.05); the medication and EA groups compared to the AGA group, the dysfunction index decreased significantly (P<0.01), the content of TNF-α and IL-lβ decreased significantly (P<0.05), the expression of TREM-l in synovial tissue decreased significantly (P<0.05); there were not statistically significant between the medication and EA group (P>0.05). EA treating AGA may be through down-regulating the expression of TREM -1 in synovial tissue.

(S)Partners for Heart Health: a school-based program for enhancing physical activity and nutrition to promote cardiovascular health in 5th grade students.

PubMed

Carlson, Joseph J; Eisenmann, Joey C; Pfeiffer, Karin A; Jager, Kathleen B; Sehnert, Scott T; Yee, Kimbo E; Klavinski, Rita A; Feltz, Deborah L

2008-12-22

The American Heart Association Position Statement on Cardiovascular Health Promotion in Public Schools encourages school-based interventions for the primary prevention of cardiovascular disease (CVD) through risk factor prevention or reduction in children with an emphasis on creating an environment that promotes healthy food choices and physical activity (PA). In an effort to address issues related to CVD risk factors including obesity in Michigan children, a multi-disciplinary team of Michigan State University (MSU) faculty, clinicians, and health profession students was formed to "(S)partner" with elementary school physical education (PE) teachers and MSU Extension staff to develop and implement a cost-effective, sustainable program aimed at CVD risk factor prevention and management for 5th grade students. This (S)partnership is intended to augment and improve the existing 5th grade PE, health and nutrition curriculum by achieving the following aims: 1) improve the students' knowledge, attitudes and confidence about nutrition, PA and heart health; 2) increase the number of students achieving national recommendations for PA and nutrition; and 3) increase the number of students with a desirable CVD risk factor status based on national pediatric guidelines. Secondary aims include promoting school staff and parental support for heart health to help children achieve their goals and to provide experiential learning and service for MSU health profession students for academic credit. This pilot effectiveness study was approved by the MSU IRB. At the beginning and the end of the school year students undergo a CVD risk factor assessment conducted by MSU medical students and graduate students. Key intervention components include eight lesson plans (conducted bi-monthly) designed to promote heart healthy nutrition and PA behaviors conducted by PE teachers with assistance from MSU undergraduate dietetic and kinesiology students (Spartners). The final 10 minutes of each lesson, MSU Spartners conduct small breakout/discussion groups with the 5th grade students. Additionally, each Spartner case manages/mentors two to three 5th grade students using a web-based goal setting and tracking protocol throughout the school year. This paper describes the rationale, development, and methods of the Spartners for Heart Health program. This is a multi-level intervention designed to promote heart healthy behaviors and prevent or manage CVD risk factors in children. We believe this will be a viable sustainable intervention that can be disseminated and adopted by other institutions with minimal cost by engaging college students as an integral part of the measurement and intervention teams.

(S)Partners for Heart Health: a school-based program for enhancing physical activity and nutrition to promote cardiovascular health in 5th grade students

PubMed Central

Carlson, Joseph J; Eisenmann, Joey C; Pfeiffer, Karin A; Jager, Kathleen B; Sehnert, Scott T; Yee, Kimbo E; Klavinski, Rita A; Feltz, Deborah L

2008-01-01

Background The American Heart Association Position Statement on Cardiovascular Health Promotion in Public Schools encourages school-based interventions for the primary prevention of cardiovascular disease (CVD) through risk factor prevention or reduction in children with an emphasis on creating an environment that promotes healthy food choices and physical activity (PA). In an effort to address issues related to CVD risk factors including obesity in Michigan children, a multi-disciplinary team of Michigan State University (MSU) faculty, clinicians, and health profession students was formed to "(S)partner" with elementary school physical education (PE) teachers and MSU Extension staff to develop and implement a cost-effective, sustainable program aimed at CVD risk factor prevention and management for 5th grade students. This (S)partnership is intended to augment and improve the existing 5th grade PE, health and nutrition curriculum by achieving the following aims: 1) improve the students' knowledge, attitudes and confidence about nutrition, PA and heart health; 2) increase the number of students achieving national recommendations for PA and nutrition; and 3) increase the number of students with a desirable CVD risk factor status based on national pediatric guidelines. Secondary aims include promoting school staff and parental support for heart health to help children achieve their goals and to provide experiential learning and service for MSU health profession students for academic credit. Methods/Design This pilot effectiveness study was approved by the MSU IRB. At the beginning and the end of the school year students undergo a CVD risk factor assessment conducted by MSU medical students and graduate students. Key intervention components include eight lesson plans (conducted bi-monthly) designed to promote heart healthy nutrition and PA behaviors conducted by PE teachers with assistance from MSU undergraduate dietetic and kinesiology students (Spartners). The final 10 minutes of each lesson, MSU Spartners conduct small breakout/discussion groups with the 5th grade students. Additionally, each Spartner case manages/mentors two to three 5th grade students using a web-based goal setting and tracking protocol throughout the school year. Discussion This paper describes the rationale, development, and methods of the Spartners for Heart Health program. This is a multi-level intervention designed to promote heart healthy behaviors and prevent or manage CVD risk factors in children. We believe this will be a viable sustainable intervention that can be disseminated and adopted by other institutions with minimal cost by engaging college students as an integral part of the measurement and intervention teams. PMID:19102777

Precipitation and Solubility of Calcium Hydrogenurate Hexahydrate

PubMed Central

Babić-Ivančić, V.; Füredi-Milhofer, H.; Brničević, N.; Marković, M.

1992-01-01

Solid phases formed in the quaternary system: uric acid—calcium hydroxide —hydrochloric acid—water aged for 2 months at 310 K were studied to determine conditions for calcium hydrogenurate hexahydrate, Ca(C5H3N4O)2 · 6H2O precipitation. The precipitates were identified by chemical and thermogravimetric analyses, x-ray powder diffraction, infrared spectroscopy, light microscopy, and scanning electron microscopy. In the precipitation diagram the concentration region in which calcium hydrogenurate hexahydrate precipitated as a single solid phase was established. The solubility of calcium hydrogenurate hexahydrate was investigated in the pH range from 6.2 to 10.1 at different temperatures. The total soluble and ionic concentration of calcium (atomic absorption spectroscopy and Ca-selective electrode), total urate concentration (spectrophotometry), and pH were determined in equilibrated solutions. The data are presented in the form of tables and chemical potential diagrams. By using these data the thermodynamic solubility products of calcium hydrogenurate hexahydrate, Ks = a(Ca2+) · a2(C5H3N4O3−), were determined: pKs=10.12±0.07at288K,pKs=9.81±0.09at298K,pKs=9.28±0.04at310K,andpKs=9.01±0.03at318K.The formation of calcium hydrogenurate hexahydrate crystals in urinary tract of patients with pathologically high concentrations of calcium and urates (hypercalciuria and hyperuricosiuria) is possible. PMID:28053438

VizieR Online Data Catalog: Nine new open clusters within 500pc from the Sun (Roser+, 2016)

NASA Astrophysics Data System (ADS)

Roser, S.; Schilbach, E.; Goldman, B.

2017-03-01

We used URAT1 (Zacharias et al., 2015, Cat. I/329) to improve the Tycho-2 proper motions and to test what proper motions, which are more precise than those of Tycho-2 (Hog et al., 2000, Cat. I/259), can do for open cluster studies. URAT1 contains 228 million objects down to about R=18.5 mag, north of about -20° declination. For the bulk of the Tycho-2 stars, URAT1 gives positions at a mean epoch around 2013.5 and an accuracy level of about 20mas per co-ordinate. We cross-matched URAT1 with Tycho-2 (the original data set tyc2.dat from CDS), and obtained new proper motions via a least-squares adjustment as described, for example in PPMXL (Roeser et al., 2010, Cat. I/317). To avoid formally ultra-precise astrometry for a small number of stars, we chose a 10mas floor for the precision of a URAT1 position. The newly detected clusterings are located in the solar neighbourhood at distances below 500pc from the Sun. The candidates RSG1 to RSG8 are very probably genuine physical groups. Membership and astrophysical parameters could be determined sufficiently well. Nevertheless, accurate parallaxes of at least several reliable cluster stars could improve the quality of parameter determination. A definite age cannot be derived for RSG9; this critically depends on the secure membership status of the two brightest stars. Table 1 summarises the astrophysical parameters of the newly found objects. (1 data file).

An extended theory of planned behavior to predict consumers' willingness to buy mobile slaughter unit meat.

PubMed

Hoeksma, Djura L; Gerritzen, Marien A; Lokhorst, Anne Marike; Poortvliet, P Marijn

2017-06-01

The current study investigated the determinants of consumers' intention to purchase meat from mobile slaughter units (MSU). The theory of planned behavior (TPB) and the value belief norm theory (VBN) were used as conceptual lenses to guide this investigation. We conducted a survey among 329 respondents in the Netherlands who buy meat for themselves and/or for others. The results indicated that (1) TPB and VBN explain a high proportion of the variance in consumers' intention to buy MSU meat, and that (2) an extended TPB that includes peoples' attitude, personal norm, subjective norm, and perceived behavioral control turned out to be the best model to predict willingness to buy MSU meat. Further implications for future research and practice are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Direct-to-Consumer Marketing: A Complementary Approach to Traditional Dissemination and implementation Efforts for Mental Health and Substance Abuse Interventions.

PubMed

Becker, Sara J

2015-03-01

The overall chasm between those who need treatment for mental health and substance abuse (M/SU) and those who receive effective treatment consists of two, interrelated gaps: the research-to-practice gap and the treatment gap. Prior efforts to disseminate evidence-based practice (EBP) for M/SU have predominantly targeted the research-to-practice gap, by focusing efforts toward treatment providers. This article introduces direct-to-consumer (DTC) marketing that targets patients and caregivers as a complementary approach to existing dissemination efforts. Specific issues discussed include: rationale for DTC marketing based on the concept of push versus pull marketing; overview of key stakeholders involved in DTC marketing; and description of the Marketing Mix planning framework. The applicability of these issues to the dissemination of EBP for M/SU is discussed.

Estimating stratospheric temperature trends using satellite microwave radiances

NASA Technical Reports Server (NTRS)

Hudson, Robert D.; Newman, Paul A.; Schoeberl, Mark R.

1990-01-01

The objective was to evaluate and intercompare stratospheric temperatures using Microwave Sounding Unit (MSU) data as a basis data set. The MSU, aboard the NOAA polar orbiter satellite series, provides twice daily global coverage over a layer (50-150 mb) at approximately a (170km)(exp 2) resolution. Conventional data sets will be compared to the satellite data in the lower stratosphere in order to assess their quality for trend computations.

Association analysis of the SLC22A11 (organic anion transporter 4) and SLC22A12 (urate transporter 1) urate transporter locus with gout in New Zealand case-control sample sets reveals multiple ancestral-specific effects

PubMed Central

2013-01-01

Introduction There is inconsistent association between urate transporters SLC22A11 (organic anion transporter 4 (OAT4)) and SLC22A12 (urate transporter 1 (URAT1)) and risk of gout. New Zealand (NZ) Māori and Pacific Island people have higher serum urate and more severe gout than European people. The aim of this study was to test genetic variation across the SLC22A11/SLC22A12 locus for association with risk of gout in NZ sample sets. Methods A total of 12 single nucleotide polymorphism (SNP) variants in four haplotype blocks were genotyped using TaqMan® and Sequenom MassArray in 1003 gout cases and 1156 controls. All cases had gout according to the 1977 American Rheumatism Association criteria. Association analysis of single markers and haplotypes was performed using PLINK and Stata. Results A haplotype block 1 SNP (rs17299124) (upstream of SLC22A11) was associated with gout in less admixed Polynesian sample sets, but not European Caucasian (odds ratio; OR = 3.38, P = 6.1 × 10-4; OR = 0.91, P = 0.40, respectively) sample sets. A protective block 1 haplotype caused the rs17299124 association (OR = 0.28, P = 6.0 × 10-4). Within haplotype block 2 (SLC22A11) we could not replicate previous reports of association of rs2078267 with gout in European Caucasian (OR = 0.98, P = 0.82) sample sets, however this SNP was associated with gout in Polynesian (OR = 1.51, P = 0.022) sample sets. Within haplotype block 3 (including SLC22A12) analysis of haplotypes revealed a haplotype with trans-ancestral protective effects (OR = 0.80, P = 0.004), and a second haplotype conferring protection in less admixed Polynesian sample sets (OR = 0.63, P = 0.028) but risk in European Caucasian samples (OR = 1.33, P = 0.039). Conclusions Our analysis provides evidence for multiple ancestral-specific effects across the SLC22A11/SLC22A12 locus that presumably influence the activity of OAT4 and URAT1 and risk of gout. Further fine mapping of the association signal is needed using trans-ancestral re-sequence data. PMID:24360580

Nephrolithiasis: Molecular Mechanism of Renal Stone Formation and the Critical Role Played by Modulators

PubMed Central

Aggarwal, Kanu Priya; Narula, Shifa; Kakkar, Monica

2013-01-01

Urinary stone disease is an ailment that has afflicted human kind for many centuries. Nephrolithiasis is a significant clinical problem in everyday practice with a subsequent burden for the health system. Nephrolithiasis remains a chronic disease and our fundamental understanding of the pathogenesis of stones as well as their prevention and cure still remains rudimentary. Regardless of the fact that supersaturation of stone-forming salts in urine is essential, abundance of these salts by itself will not always result in stone formation. The pathogenesis of calcium oxalate stone formation is a multistep process and essentially includes nucleation, crystal growth, crystal aggregation, and crystal retention. Various substances in the body have an effect on one or more of the above stone-forming processes, thereby influencing a person's ability to promote or prevent stone formation. Promoters facilitate the stone formation while inhibitors prevent it. Besides low urine volume and low urine pH, high calcium, sodium, oxalate and urate are also known to promote calcium oxalate stone formation. Many inorganic (citrate, magnesium) and organic substances (nephrocalcin, urinary prothrombin fragment-1, osteopontin) are known to inhibit stone formation. This review presents a comprehensive account of the mechanism of renal stone formation and the role of inhibitors/promoters in calcium oxalate crystallisation. PMID:24151593

Tubular urate transporter gene polymorphisms differentiate patients with gout who have normal and decreased urinary uric acid excretion.

PubMed

Torres, Rosa J; de Miguel, Eugenio; Bailén, Rebeca; Banegas, José R; Puig, Juan G

2014-09-01

Primary gout has been associated with single-nucleotide polymorphisms (SNP) in several tubular urate transporter genes. No study has assessed the association of reabsorption and secretion urate transporter gene SNP with gout in a single cohort of documented primary patients with gout carefully subclassified as normoexcretors or underexcretors. Three reabsorption SNP (SLC22A12/URAT1, SLC2A9/GLUT9, and SLC22A11/OAT4) and 2 secretion transporter SNP (SLC17A1/NPT1 and ABCG2/BRCP) were studied in 104 patients with primary gout and in 300 control subjects. The patients were subclassified into normoexcretors and underexcretors according to their serum and 24-h urinary uric acid levels under strict conditions of dietary control. Compared with control subjects, patients with gout showed different allele distributions of the 5 SNP analyzed. However, the diagnosis of underexcretor was only positively associated with the presence of the T allele of URAT1 rs11231825, the G allele of GLUT9 rs16890979, and the A allele of ABCG2 rs2231142. The association of the A allele of ABCG2 rs2231142 in normoexcretors was 10 times higher than in underexcretors. The C allele of NPT1 rs1165196 was only significantly associated with gout in patients with normal uric acid excretion. Gout with uric acid underexcretion is associated with transporter gene SNP related mainly to tubular reabsorption, whereas uric acid normoexcretion is associated only with tubular secretion SNP. This finding supports the concept of distinctive mechanisms to account for hyperuricemia in patients with gout with reduced or normal uric acid excretion.

Population-specific influence of SLC2A9 genotype on the acute hyperuricaemic response to a fructose load.

PubMed

Dalbeth, Nicola; House, Meaghan E; Gamble, Gregory D; Horne, Anne; Pool, Bregina; Purvis, Lauren; Stewart, Angela; Merriman, Marilyn; Cadzow, Murray; Phipps-Green, Amanda; Merriman, Tony R

2013-11-01

SLC2A9 is a strong genetic risk factor for hyperuricaemia and gout. SLC2A9 (GLUT9) is a high capacity urate transporter and reportedly transports glucose and fructose. Intake of fructose-containing beverages is associated with development of hyperuricaemia and gout. To determine whether genetic variation in SLC2A9 influences the acute serum urate response to a fructose load. Following an overnight fast, 76 healthy volunteers (25 Māori, 26 Pacific, 25 European Caucasian) drank a solution containing 64 g fructose. Serum and urine were obtained immediately before and then 30, 60, 120 and 180 min after ingestion. The SLC2A9 single nucleotide polymorphism (SNP) rs11942223 was genotyped and data were analysed based on the presence or absence of the gout protective minor allele (C). The rs11942223 C allele was present in 17 participants (22%). In the entire group, fructose intake led to an increase in serum urate, which peaked 60 min following fructose ingestion (analysis of variance p=0.006). The presence of the C allele was associated with an attenuated hyperuricaemic response (p(SNP)<0.0001) and increased fractional excretion of uric acid (FEUA) (p(SNP)<0.0001) following the fructose load. The effects of rs11942223 variants on serum urate and FEUA in response to fructose were present only in Caucasian ancestral subgroups but not in the Māori and Pacific ancestral subgroup. Variation in SLC2A9 influences acute serum urate and FEUA responses to a fructose load. SLC2A9 genotype may influence the development of gout on exposure to fructose-containing beverages, particularly in European Caucasian populations.

Safety and efficacy of oral febuxostat for treatment of HLA-B*5801-negative gout: a randomized, open-label, multicentre, allopurinol-controlled study

PubMed Central

Yu, K-H; Lai, J-H; Hsu, P-N; Chen, D-Y; Chen, C-J; Lin, H-Y

2016-01-01

Objectives: This phase IIIB study compared the efficacy and safety of febuxostat and allopurinol in gout patients with or without tophi who were HLA-B*5801 negative. Method: Eligible patients were randomized to a febuxostat group (80 mg QD) or an allopurinol group (300 mg QD). Following an initial 2-week washout period, over the next 12 weeks we made five measurements of serum urate levels along with assessments of adverse events (AEs). Results: Forty-three out of 152 screened subjects (28.3%) were ineligible either because of the presence of the HLA-B*5801 allele or for various other reasons. The febuxostat group (n = 54) and the allopurinol group (n = 55) had no significant differences in demographic or baseline characteristics. From week 2 to week 12, the febuxostat group had a significantly lower serum urate level than the allopurinol group (p ≤ 0.001 for all comparisons) and significantly more patients with serum urate levels less than 6.0 mg/dL. The serum urate levels of the febuxostat group declined by more than 40% from week 2 to week 12 and this decrease was greater than that in the allopurinol group (~30%). The two groups were similar in terms of AEs. Conclusions: Febuxostat was more effective than allopurinol in reducing the serum urate levels of Han Chinese patients with gout or tophaceous gout who were HLA-B*5801 negative, without causing any serious skin reactions. Febuxostat should be considered for treatment of Han Chinese patients with gout who are HLA-B*5801 negative. PMID:26771445

Safety and efficacy of oral febuxostat for treatment of HLA-B*5801-negative gout: a randomized, open-label, multicentre, allopurinol-controlled study.

PubMed

Yu, K-H; Lai, J-H; Hsu, P-N; Chen, D-Y; Chen, C-J; Lin, H-Y

2016-07-01

This phase IIIB study compared the efficacy and safety of febuxostat and allopurinol in gout patients with or without tophi who were HLA-B*5801 negative. Eligible patients were randomized to a febuxostat group (80 mg QD) or an allopurinol group (300 mg QD). Following an initial 2-week washout period, over the next 12 weeks we made five measurements of serum urate levels along with assessments of adverse events (AEs). Forty-three out of 152 screened subjects (28.3%) were ineligible either because of the presence of the HLA-B*5801 allele or for various other reasons. The febuxostat group (n = 54) and the allopurinol group (n = 55) had no significant differences in demographic or baseline characteristics. From week 2 to week 12, the febuxostat group had a significantly lower serum urate level than the allopurinol group (p ≤ 0.001 for all comparisons) and significantly more patients with serum urate levels less than 6.0 mg/dL. The serum urate levels of the febuxostat group declined by more than 40% from week 2 to week 12 and this decrease was greater than that in the allopurinol group (~30%). The two groups were similar in terms of AEs. Febuxostat was more effective than allopurinol in reducing the serum urate levels of Han Chinese patients with gout or tophaceous gout who were HLA-B*5801 negative, without causing any serious skin reactions. Febuxostat should be considered for treatment of Han Chinese patients with gout who are HLA-B*5801 negative.

A survey on the beliefs and knowledge of gout management in new medical graduates - New South Wales, Australia.

PubMed

Terrill, Matthew; Riordan, John

2018-02-01

To assess the beliefs and knowledge of gout management in new medical graduates. A survey on gout management was sent to new medical graduates during their orientation week, New South Wales, Australia. 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 37.2% for chronic gout. In an acute gout flare, 63.4% answered they would continue urate lowering therapy and 67.2% were aware of first-line pharmacological management options; 28% answered the correct dosing regimen for colchicine. Chronic management was answered poorly. Only 42.0% stated they would titrate allopurinol dosing to a target urate level; 23.5% would check the urate level monthly. More than half, 56.8%, were aware that medical prophylaxis is indicated when initiating urate lowering therapy. Of this subgroup, 46.7% (25.9% overall) knew that non-steroidal anti-inflammatory drugs and colchicine were recommended and 28.4% (15.4% overall) answered the correct timeframe of use. Close to one-third (35.0%), were aware of febuxostat, probenecid and benzbromarone as second-line urate lowering therapy. The findings of this study suggest that new graduates' knowledge of gout management, especially chronic management, is suboptimal. Many felt their teaching on gout management inadequate; this is a potential target for intervention. Up to date university education which covers chronic management may lead to better clinical outcomes for this burdensome disease. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Zurampic Protects Pancreatic β-Cells from High Uric Acid Induced-Damage by Inhibiting URAT1 and Inactivating the ROS/AMPK/ERK Pathways.

PubMed

Xin, Ying; Wang, Kun; Jia, Zhaotong; Xu, Tao; Xu, Qiang; Zhang, Chao; Liu, Jia; Chen, Rui; Du, Zhongcai; Sun, Jianjing

2018-05-25

Zurampic is a US FDA approved drug for treatment of gout. However, the influence of Zurampic on pancreatic β-cells remains unclear. The study aimed to evaluate the effects of Zurampic on high uric acid-induced damage of pancreatic β-cells and the possible underlying mechanisms. INS-1 cells and primary rat islets were stimulated with Zurampic and the mRNA expression of urate transporter 1 (URAT1) was assessed by qRT-PCR. Cells were stimulated with uric acid or uric acid plus Zurampic, and cell viability, apoptosis and ROS release were measured by MTT and flow cytometry assays. Western blot analysis was performed to evaluate the expressions of active Caspase-3 and phosphorylation of AMPK and ERK. Finally, cells were stimulated with uric acid or uric acid plus Zurampic at low/high level of glucose (2.8/16.7 mM glucose), and the insulin release was assessed by ELISA. mRNA expression of URAT1 was decreased by Zurampic in a dose-dependent manner. Uric acid decreased cell viability, promoted cell apoptosis and induced ROS release. Uric acid-induced alterations could be reversed by Zurampic. Activation of Caspase-3 and phosphorylation of AMPK and ERK were enhanced by uric acid, and the enhancements were reversed by Zurampic. Decreased phosphorylation of AMPK and ERK, induced by Zurampic, was further reduced by adding inhibitor of AMPK or ERK. Besides, uric acid inhibited high glucose-induced insulin secretion and the inhibition was rescued by Zurampic. Zurampic has a protective effect on pancreatic β-cells against uric acid induced-damage by inhibiting URAT1 and inactivating the ROS/AMPK/ERK pathway. © 2018 The Author(s). Published by S. Karger AG, Basel.

Placement into First College Mathematics Course: A Comparison of the Results of the Michigan State University Proctored Mathematics Placement Examination and the Unproctored Mathematics Placement Examination

ERIC Educational Resources Information Center

Drake, Samuel

2010-01-01

The primary purpose of this study was to compare the results of the Michigan State University (MSU) unproctored examination to the results of the proctored examination. Both examinations are used to determine whether first time freshmen at MSU are ready for a standard mathematics course or if a remedial course is necessary. In addition to…

Direct-to-Consumer Marketing: A Complementary Approach to Traditional Dissemination and implementation Efforts for Mental Health and Substance Abuse Interventions

PubMed Central

Becker, Sara J.

2014-01-01

The overall chasm between those who need treatment for mental health and substance abuse (M/SU) and those who receive effective treatment consists of two, interrelated gaps: the research-to-practice gap and the treatment gap. Prior efforts to disseminate evidence-based practice (EBP) for M/SU have predominantly targeted the research-to-practice gap, by focusing efforts toward treatment providers. This article introduces direct-to-consumer (DTC) marketing that targets patients and caregivers as a complementary approach to existing dissemination efforts. Specific issues discussed include: rationale for DTC marketing based on the concept of push versus pull marketing; overview of key stakeholders involved in DTC marketing; and description of the Marketing Mix planning framework. The applicability of these issues to the dissemination of EBP for M/SU is discussed. PMID:25937710

Global Warming: Evidence from Satellite Observations

NASA Technical Reports Server (NTRS)

Prabhakara, C.; Iacovazzi, R.; Yoo, J.-M.; Dalu, G.; Einaudi, Franco (Technical Monitor)

2000-01-01

Observations made in Channel 2 (53.74 GHz) of the Microwave Sounding Unit (MSU) radiometer, flown onboard sequential, sun-synchronous, polar-orbiting NOAA (National Oceanic and Atmospheric Administration) operational satellites, indicate that the mean temperature of the atmosphere over the globe increased during the period 1980 to 1999. In this study, we have minimized systematic errors in the time series introduced by satellite orbital drift in an objective manner. This is done with the help of the onboard warm-blackbody temperature, which is used in the calibration of the MSU radiometer. The corrected MSU Channel 2 observations of the NOAA satellite series reveal that the vertically-weighted global-mean temperature of the atmosphere, with a peak weight near the mid troposphere, warmed at the rate of 0.13 +/- 0.05 K/decade during 1980 to 1999. The global warming deduced from conventional meteorological data that have been corrected for urbanization effects agrees reasonably with this satellite-deduced result.

Celebrating Einstein

NASA Astrophysics Data System (ADS)

Key, Joey; Yunes, Nicolas

2013-04-01

The Gravity Group at Montana State University (MSU) hosted Celebrating Einstein, a free public arts and multimedia event celebrating Einstein and his ideas in Bozeman, Montana April 2-6, 2013. The products of our efforts are now available to any party interested in hosting a similar event. Celebrating Einstein is a truly interdisciplinary effort including art, film, dance, music, physics, history, and education. Events included a black hole immersive art installation, a series of public talks by physicists, and Einstein lessons in the public schools leading up to a live free public multimedia performance including a professional dance company, a live interview with a renowned physicist, and an original score composed for the MSU student symphony to be performed with an original film produced by the Science and Natural History film program at MSU. This project is funded by the Montana Space Grant Consortium, Montana State University, and the National Science Foundation.

Febuxostat for the chronic management of hyperuricemia in patients with gout.

PubMed

Chinchilla, Sandra Pamela; Urionaguena, Irati; Perez-Ruiz, Fernando

2016-01-01

Febuxostat is a non-purine, selective inhibitor of both isoforms of xanthine oxido-reductase (XOR), and a major alternative to the scarce number of urate-lowering medications available in the last decades. Its inhibition of XOR is more potent than allopurinol in a mg to mg comparison, what is associated to achievement of serum urate target more frequently than allopurinol at doses tested in clinical trials, especially in patients with the highest baseline serum urate levels. Its pharmacokinetics is not greatly dependent on renal clearance, contrary to allopurinol, what may be an advantage in patients with chronic kidney disease. Several trials are further evaluating both the cardiovascular safety of febuxostat and its possible beneficial effect on renal function preservation. Still scarce, but clinically interesting, evidence on its use in transplant patients has been recently released.

Ascorbic acid interference in the measurement of serum biochemical parameters: in vivo and in vitro studies.

PubMed

Martinello, Flávia; da Silva, Edson Luiz

2006-04-01

To investigate the negative interference of ascorbic acid in serum biochemical tests in relation to the dose of vitamin C intake and to the time of blood collection. Healthy volunteers (n = 18) consumed daily doses of vitamin C (0.25-4.0 g) for 1 week and serum parameters were assayed prior to the experiment and on the eighth day of consumption. Blood samples were collected 4, 12 and 24 h after vitamin C intake. Serum levels of ascorbic acid increased significantly after vitamin C ingestion inhibiting urate and total bilirubin tests 4 and 12 h after intake (P < 0.01). A significant negative interference occurred up to 24 h after consumption of 4 g vitamin C for the urate test. In contrast, ingestion of vitamin C did not show interference in glucose, triglyceride and cholesterol tests. Addition of ascorbic acid to serum inhibited the urate test to a similar extent to that observed after vitamin C intake. However, after ingesting vitamin C, the interference for the bilirubin test was greater than that of the in vitro interference. Commonly taken doses of supplementary vitamin C interfered negatively with the serum urate test based on the Trinder method, and with bilirubin metabolism.

Using satellite data on meteorological and vegetation characteristics and soil surface humidity in the Land Surface Model for the vast territory of agricultural destination

NASA Astrophysics Data System (ADS)

Muzylev, Eugene; Startseva, Zoya; Uspensky, Alexander; Vasilenko, Eugene; Volkova, Elena; Kukharsky, Alexander

2017-04-01

The model of water and heat exchange between vegetation covered territory and atmosphere (LSM, Land Surface Model) for vegetation season has been developed to calculate soil water content, evapotranspiration, infiltration of water into the soil, vertical latent and sensible heat fluxes and other water and heat balances components as well as soil surface and vegetation cover temperatures and depth distributions of moisture and temperature. The LSM is suited for utilizing satellite-derived estimates of precipitation, land surface temperature and vegetation characteristics and soil surface humidity for each pixel. Vegetation and meteorological characteristics being the model parameters and input variables, correspondingly, have been estimated by ground observations and thematic processing measurement data of scanning radiometers AVHRR/NOAA, SEVIRI/Meteosat-9, -10 (MSG-2, -3) and MSU-MR/Meteor-M № 2. Values of soil surface humidity has been calculated from remote sensing data of scatterometers ASCAT/MetOp-A, -B. The case study has been carried out for the territory of part of the agricultural Central Black Earth Region of European Russia with area of 227300 km2 located in the forest-steppe zone for years 2012-2015 vegetation seasons. The main objectives of the study have been: - to built estimates of precipitation, land surface temperatures (LST) and vegetation characteristics from MSU-MR measurement data using the refined technologies (including algorithms and programs) of thematic processing satellite information matured on AVHRR and SEVIRI data. All technologies have been adapted to the area of interest; - to investigate the possibility of utilizing satellite-derived estimates of values above in the LSM including verification of obtained estimates and development of procedure of their inputting into the model. From the AVHRR data there have been built the estimates of precipitation, three types of LST: land skin temperature Tsg, air temperature at a level of vegetation cover (taken for vegetation temperature) Ta and efficient radiation temperature Ts.eff, as well as land surface emissivity E, normalized difference vegetation index NDVI, vegetation cover fraction B, and leaf area index LAI. The SEVIRI-based retrievals have included precipitation, LST Tls and Ta, E at daylight and nighttime, LAI (daily), and B. From the MSU-MR data there have been retrieved values of all the same characteristics as from the AVHRR data. The MSU-MR-based daily and monthly sums of precipitation have been calculated using the developed earlier and modified Multi Threshold Method (MTM) intended for the cloud detection and identification of its types around the clock as well as allocation of precipitation zones and determination of instantaneous maximum rainfall intensities for each pixel at that the transition from assessing rainfall intensity to estimating their daily values is a key element of the MTM. Measurement data from 3 IR MSU-MR channels (3.8, 11 i 12 μm) as well as their differences have been used in the MTM as predictors. Controlling the correctness of the MSU-MR-derived rainfall estimates has been carried out when comparing with analogous AVHRR- and SEVIRI-based retrievals and with precipitation amounts measured at the agricultural meteorological station of the study region. Probability of rainfall zones determination from the MSU-MR data, to match against the actual ones, has been 75-85% as well as for the AVHRR and SEVIRI data. The time behaviors of satellite-derived and ground-measured daily and monthly precipitation sums for vegetation season and yeaŗ correspondingly, have been in good agreement with each other although the first ones have been smoother than the latter. Discrepancies have existed for a number of local maxima for which satellite-derived precipitation estimates have been less than ground-measured values. It may be due to the different spatial scales of areal satellite-derived and point ground-based estimates. Some spatial displacement of the satellite-determined rainfall maxima and minima regarding to ground-based data can be explained by the discrepancy between the cloud location on satellite images and in reality at high angles of the satellite sightings and considerable altitudes of the cloud tops. Reliability of MSU-MR-derived rainfall estimates at each time step obtained using the MTM has been verified by comparing their values determined from the MSU-MR, AVHRR and SEVIRI measurements and distributed over the study area with similar estimates obtained by interpolation of ground observation data. The MSU-MR-derived estimates of temperatures Tsg, Ts.eff, and Ta have been obtained using computational algorithm developed on the base of the MTM and matured on AVHRR and SEVIRI data for the region under investigation. Since the apparatus MSU-MR is similar to radiometer AVHRR, the developed methods of satellite estimating Tsg, Ts.eff, and Ta from AVHRR data could be easily transferred to the MSU-MR data. Comparison of the ground-measured and MSU-MR-, AVHRR- and SEVIRI-derived LSTs has shown that the differences between all the estimates for the vast majority of observation terms have not exceed the RMSE of these quantities built from the AVHRR data. The similar conclusion has been also made from the results of building the time behavior of the MSU-MR-derived value of LAI for vegetation season. Satellite-based estimates of precipitation, LST, LAI and B have been utilized in the model with the help of specially developed procedures of replacing these values determined from observations at agricultural meteorological stations by their satellite-derived values taking into account spatial heterogeneity of their fields. Adequacy of such replacement has been confirmed by the results of comparing modeled and ground-measured values of soil moisture content W and evapotranspiration Ev. Discrepancies between the modeled and ground-measured values of W and Ev have been in the range of 10-15 and 20-25 %, correspondingly. It may be considered as acceptable result. Resulted products of the model calculations using satellite data have been spatial fields of W, Ev, vertical sensible and latent heat fluxes and other water and heat regime characteristics for the region of interest over the year 2012-2015 vegetation seasons. Thus, there has been shown the possibility of utilizing MSU-MR/Meteor-M №2 data jointly with those of other satellites in the LSM to calculate characteristics of water and heat regimes for the area under consideration. Besides the first trial estimations of the soil surface moisture from ASCAT scatterometers data for the study region have been obtained for the years 2014-2015 vegetation seasons, their comparison has been performed with the results of modeling for several agricultural meteorological stations of the region that has been carried out utilizing ground-based and satellite data, specific requirements for the obtained information have been formulated. To date, estimates of surface moisture built from ASCAT data can be used for the selection of the model soil parameter values and the initial soil moisture conditions for the vegetation season.

Ultrasound sensitivity to changes in gout: a longitudinal study after two years of treatment.

PubMed

Peiteado, Diana; Villalba, Alejandro; Martín-Mola, Emilio; Balsa, Alejandro; De Miguel, Eugenio

2017-01-01

The goals of our study are to evaluate the urate-lowering therapy (ULT) effect on gout ultrasound (US) lesions and to explore US sensitivity to change in gout patients. Patients with chronic and symptomatic gout, confirmed by crystal identification, were prospectively included. Clinical and US assessments were performed at baseline and after 6, 12 and 24 months of ULT. The presence of double contour sign (DCS) and US- detectable tophi were assessed in the first metatarsophalangeals, the knees and patellar tendons. The mean and standard deviation were calculated for each parameter. The correlation between the clinical and US parameters was assessed by calculating Pearson's correlation coefficient. Sensitivity to change in the US examinations was assessed by estimating the smallest detectable difference (SDD). Twenty-three consecutive patients were included (96% men; mean age 59 ± 11 years). DCS and US tophi were detected in 73.9% and 91.3% of patients at baseline. A significant parallel improvement in the serum urate, clinical parameters and US lesions was found at the follow-up assessment. The SDD values for the global DCS and tophi were 0.52 and 0.69, respectively, which were smaller than the differences achieved over the course of the two years. A significant correlation between DCS and clinical parameters was observed (r =0.49, p=0.038). Ultrasound findings in gout patients show sensitivity to change and concurrent validity with uric acid reduction after ULT in gout patients. US can be a useful tool for gout tophus burden monitoring.

Pharmacophore modeling, molecular docking and molecular dynamics studies on natural products database to discover novel skeleton as non-purine xanthine oxidase inhibitors.

PubMed

Peng, Jiale; Li, Yaping; Zhou, Yeheng; Zhang, Li; Liu, Xingyong; Zuo, Zhili

2018-05-29

Gout is a common inflammatory arthritis caused by the deposition of urate crystals within joints. It is increasingly in prevalence during the past few decades as shown by the epidemiological survey results. Xanthine oxidase (XO) is a key enzyme to transfer hypoxanthine and xanthine to uric acid, whose overproduction leads to gout. Therefore, inhibiting the activity of xanthine oxidase is an important way to reduce the production of urate. In the study, in order to identify the potential natural products targeting XO, pharmacophore modeling was employed to filter databases. Here, two methods, pharmacophore based on ligand and pharmacophore based on receptor-ligand, were constructed by Discovery Studio. Then GOLD was used to refine the potential compounds with higher fitness scores. Finally, molecular docking and dynamics simulations were employed to analyze the interactions between compounds and protein. The best hypothesis was set as a 3D query to screen database, returning 785 and 297 compounds respectively. A merged set of the above 1082 molecules was subjected to molecular docking, which returned 144 hits with high-fitness scores. These molecules were clustered in four main kinds depending on different backbones. What is more, molecular docking showed that the representative compounds established key interactions with the amino acid residues in the protein, and the RMSD and RMSF of molecular dynamics results showed that these compounds can stabilize the protein. The information represented in the study confirmed previous reports. And it may assist to discover and design new backbones as potential XO inhibitors based on natural products.

The unwelcome visitor.

PubMed

Teng, Gim Gee; Tong, Chung Yan; How, Choon How; Goh, Lay Hoon

2012-08-01

Gout is a chronic, progressive inflammatory disease with intermittent arthritic flares, which should not be regarded as a minor inconvenience or nuisance. It can be effectively controlled when the patient's serum urate level is reduced to less than 360 μmol/l (6 mg/dL) by consistent use of urate-lowering pharmacotherapy. Colchicine prophylaxis for gouty flares during titration of urate-lowering therapy has been underused. Holistic long-term management of gout must encompass patient education, evidence-based dietary advice, screening and aggressive treatment of comorbidities such as hypertension, diabetes mellitus, dyslipidaemia and renal impairment. Acute therapies for recurrent attacks with non-steroidal anti-inflammatory drugs, colchicine and/or corticosteroids should be used judiciously, especially in the elderly, due to the risk of toxicities. With appreciation of the underlying pathogenesis and artful use of the limited drug options, control of gout can be effectively achieved, bringing tremendous satisfaction to the patient and doctor.

Gout and hyperuricemia.

PubMed

Wortmann, Robert L

2002-05-01

Gout continues to be a health problem around the world despite the availability of effective therapies. Although the prevalence is influenced by genetic factors, the associations of alcohol consumption, obesity, and hypertension appear to be partially responsible for the increased prevalence of gout and hyperuricemia in African and Oriental countries. The association between hyperuricemia and cardiovascular disease seems linked to insulin resistance. This relation, in part, explains the common coexistence of hyperlipidemia and glucose intolerance in patients with gout. Accordingly, it is recommended that one pay more attention to dietary manipulation in patients with gout in addition to managing hypertension, obesity, and other medical problems. Although acute gout attacks can be treated, eliminating gout requires effective removal of urate from the body. Allopurinol remains a dominant urate-lowering agent, however its use may be limited by allergic reactions. Uricosuric agents are also effective urate-lowering agents and provide an alternative to allopurinol. Strategies to treat patients who are sensitive to allopurinol continue to evolve.

Global Warming Estimation From Microwave Sounding Unit

NASA Technical Reports Server (NTRS)

Prabhakara, C.; Iacovazzi, R., Jr.; Yoo, J.-M.; Dalu, G.

1998-01-01

Microwave Sounding Unit (MSU) Ch 2 data sets, collected from sequential, polar-orbiting, Sun-synchronous National Oceanic and Atmospheric Administration operational satellites, contain systematic calibration errors that are coupled to the diurnal temperature cycle over the globe. Since these coupled errors in MSU data differ between successive satellites, it is necessary to make compensatory adjustments to these multisatellite data sets in order to determine long-term global temperature change. With the aid of the observations during overlapping periods of successive satellites, we can determine such adjustments and use them to account for the coupled errors in the long-term time series of MSU Ch 2 global temperature. In turn, these adjusted MSU Ch 2 data sets can be used to yield global temperature trend. In a pioneering study, Spencer and Christy (SC) (1990) developed a procedure to derive the global temperature trend from MSU Ch 2 data. Such a procedure can leave unaccounted residual errors in the time series of the temperature anomalies deduced by SC, which could lead to a spurious long-term temperature trend derived from their analysis. In the present study, we have developed a method that avoids the shortcomings of the SC procedure, the magnitude of the coupled errors is not determined explicitly. Furthermore, based on some assumptions, these coupled errors are eliminated in three separate steps. Such a procedure can leave unaccounted residual errors in the time series of the temperature anomalies deduced by SC, which could lead to a spurious long-term temperature trend derived from their analysis. In the present study, we have developed a method that avoids the shortcomings of the SC procedures. Based on our analysis, we find there is a global warming of 0.23+/-0.12 K between 1980 and 1991. Also, in this study, the time series of global temperature anomalies constructed by removing the global mean annual temperature cycle compares favorably with a similar time series obtained from conventional observations of temperature.

Improved mb-Ms Discrimination Using mb(P-coda) and MsU with Application to the Six North Korean Nuclear Tests

NASA Astrophysics Data System (ADS)

Napoli, V.; Yoo, S. H.; Russell, D. R.

2017-12-01

To improve discrimination of small explosions and earthquakes, we developed a new magnitude scale based on the standard Ms:mb discrimination method. In place of 20 second Ms measurements we developed a unified Rayleigh and Love wave magnitude scale (MsU) that is designed to maximize available information from single stations and then combine magnitude estimates into network averages. Additionally, in place of mb(P) measurements we developed an mb(P-Coda) magnitude scale as the properties of the coda make sparse network mb(P-Coda) more robust and less variable than network mb(P) estimates. A previous mb:MsU study conducted in 2013 in the Korean Peninsula shows that the use of MsU in place of standard 20 second Ms, leads to increased population separation and reduced scattering. The goals of a combined mb(P-coda):MsU scale are reducing scatter, ensuring applicability at small magnitudes with sparse networks, and improving the overall distribution for mb:Ms earthquake and explosion populations. To test this method we are calculating mb(P-coda)and MsU for a catalog earthquakes located in and near the Korean Peninsula, for the six North Korean nuclear tests (4.1 < mb < 6.3) and for the 3 aftershocks to date that occurred after the sixth test (2.6 < ML < 4.0). Compared to the previous 2013 study, we expect to see greater separation in the populations and less scattering with the inclusion of mb(P-coda) and with the implementation of additional filters for MsU to improve signal-to-noise levels; this includes S-transform filtering for polarization and off-azimuth signal reduction at regional distances. As we are expanding our database of mb(P-coda):MsU measurements in the Korean Peninsula to determine the earthquake and explosion distribution, this research will address the limitations and potential for discriminating small magnitude events using sparse networks.

A multi-year comparison of lower stratospheric temperatures from CHAMP radio occultation data with MSU/AMSU records

NASA Astrophysics Data System (ADS)

Steiner, A. K.; Kirchengast, G.; Borsche, M.; Foelsche, U.; Schoengassner, T.

2007-11-01

Long-term upper air temperature records have been established by different groups with considerable effort from radiosonde data and from satellite based (Advanced) Microwave Sounding Unit (MSU/AMSU) measurements, the latter providing information on layer-average stratospheric and tropospheric brightness temperatures. Comparisons of the temperature series show discrepancies not only with respect to radiosonde data but also between MSU data sets stemming from different retrievals. In this context the Global Navigation Satellite System radio occultation (RO) technique offers new possibilities by providing high quality observations of the atmosphere in an active limb sounding mode. RO temperature climatologies have been constructed at the WegCenter/UniGraz based on RO observations of the CHAllenging Minisatellite Payload for geoscientific research (CHAMP) satellite since September 2001, and based on a few months of RO data from other satellite missions (SAC-C, GRACE, COSMIC). Focusing on the MSU lower stratosphere channel (TLS), synthetic TLS temperatures were calculated by applying global weighting functions to zonal-mean monthly mean RO temperature climatology profiles for September 2001-December 2006. These synthetic CHAMP TLS temperatures were compared to recent MSU TLS records from the University of Alabama in Huntsville (UAH, USA) and from Remote Sensing Systems (RSS, USA), as well as to synthetic TLS temperatures from HadAT2 radiosonde data (Hadley Centre/MetOffice, UK) and ECMWF (European Centre for Medium-Range Weather Forecasts) analyses. In terms of TLS temperature anomalies, overall very good agreement of CHAMP temperature anomalies with UAH, RSS, and ECMWF anomalies was found for intra-annual variability (RMS difference of de-trended data <0.1 K globally, 0.1 K in the tropics, <0.25 K in the extratropics), while HadAT2 anomalies show larger differences (factor of two globally and more in the extratropics). Regarding 2001-2006 trends, UAH and RSS exhibit a statistically significant cooling trend difference to CHAMP globally (-0.30 to -0.36 K/5 yrs), stemming mainly from the tropics (-0.40 to -0.42 K/5 yrs), while in the extratropics the cooling trend differences are not significant. The contribution of known error sources regarding the RO data and the related synthetic-MSU computation procedure is about an order of magnitude smaller than these trend differences. Resolution of the trend discrepancy thus requires either additional, so far overlooked, sources of error in the RO TLS record or the presence of currently unresolved biases in the MSU records. SAC-C, GRACE, and COSMIC TLS temperatures closely match CHAMP temperatures, indicating the consistency and homogeneity of the RO data series. The results underpin the benefit of having multiple independent estimates of the same variable from different instruments for detecting residual weaknesses in otherwise high-quality climate records. Continued inter-comparison, and exploiting the traceability of the RO data to the universal time standard (UTC), then enables us to further reduce the uncertainty in the climate records in absolute terms.

Ammonium acid urate urinary stone caused by a low-caloric diet: a case report.

PubMed

Nakamura, Kogenta; Kokubo, Hiroto; Kato, Keitaro; Aoki, Shigeyuki; Taki, Tomohiro; Mitsui, Kenji; Yamada, Yoshiaki; Honda, Nobuaki; Fukatsu, Hidetoshi; Kamijo, Ayumi

2002-08-01

A 32-year-old woman complained of right back pain and pyuria. The plain radiograph (KUB) and drip infusion pyelography (DIP) demonstrated a right renal stone and hydronephrosis. The stone was successfully treated using extracorporeal shock wave lithotripsy. Infrared spectrophotometry revealed that the stone was composed of pure ammonium acid urate. The patient had a 3-year history of excessive anorexia. The low-caloric diet was considered to have caused the disease.

Clinical efficacy and safety of topiroxostat in Japanese hyperuricemic patients with or without gout: a randomized, double-blinded, controlled phase 2b study.

PubMed

Hosoya, Tatsuo; Sasaki, Tomomitsu; Ohashi, Tetsuo

2017-03-01

Topiroxostat, a selective xanthine oxidoreductase inhibitor, is used in Japan for the treatment of hyperuricemic patients with or without gout. In terms of the effectiveness of topiroxostat in lowering serum urate levels, the dose-response relationship has been evaluated; however, it remains to be verified. A randomized, multi-center, double-blinded study of topiroxostat was performed for Japanese hyperuricemic patients with or without gout. During the 16-week study, 157 Japanese hyperuricemic patients with or without gout were randomly assigned to receive a placebo, topiroxostat at 120 or 160 mg/day, or allopurinol at 200 mg/day. The primary endpoint of this study was to determine the lowering rate of serum uric acid levels compared to those of baseline at the end of administration. A dose-response relationship (regarding decreases in the serum urate levels) was confirmed for the placebo and topiroxostat at 120 and at 160 mg/day. Moreover, at the end of administration, the lowering rate of serum urate levels was determined to be -44.8% in the topiroxostat 160-mg/day group. No significant difference in the incidence of adverse events was observed among all groups, including the allopurinol group. The serum urate-lowering effect of topiroxostat was found to have a dose-response relationship in Japanese hyperuricemic patients with or without gout.

Additive composite ABCG2, SLC2A9 and SLC22A12 scores of high-risk alleles with alcohol use modulate gout risk.

PubMed

Tu, Hung-Pin; Chung, Chia-Min; Min-Shan Ko, Albert; Lee, Su-Shin; Lai, Han-Ming; Lee, Chien-Hung; Huang, Chung-Ming; Liu, Chiu-Shong; Ko, Ying-Chin

2016-09-01

The aim of the present study was to evaluate the contribution of urate transporter genes and alcohol use to the risk of gout/tophi. Eight variants of ABCG2, SLC2A9, SLC22A12, SLC22A11 and SLC17A3 were genotyped in male individuals in a case-control study with 157 gout (33% tophi), 106 asymptomatic hyperuricaemia and 295 control subjects from Taiwan. The multilocus profiles of the genetic risk scores for urate gene variants were used to evaluate the risk of asymptomatic hyperuricaemia, gout and tophi. ABCG2 Q141K (T), SLC2A9 rs1014290 (A) and SLC22A12 rs475688 (C) under an additive model and alcohol use independently predicted the risk of gout (respective odds ratio for each factor=2.48, 2.03, 1.95 and 2.48). The additive composite Q141K, rs1014290 and rs475688 scores of high-risk alleles were associated with gout risk (P<0.0001). We observed the supramultiplicative interaction effect of genetic urate scores and alcohol use on gout and tophi risk (P for interaction=0.0452, 0.0033). The synergistic effect of genetic urate score 5-6 and alcohol use indicates that these combined factors correlate with gout and tophi occurrence.

Global Warming Estimation from MSU

NASA Technical Reports Server (NTRS)

Prabhakara, C.; Iacovazzi, Robert, Jr.

1999-01-01

In this study, we have developed time series of global temperature from 1980-97 based on the Microwave Sounding Unit (MSU) Ch 2 (53.74 GHz) observations taken from polar-orbiting NOAA operational satellites. In order to create these time series, systematic errors (approx. 0.1 K) in the Ch 2 data arising from inter-satellite differences are removed objectively. On the other hand, smaller systematic errors (approx. 0.03 K) in the data due to orbital drift of each satellite cannot be removed objectively. Such errors are expected to remain in the time series and leave an uncertainty in the inferred global temperature trend. With the help of a statistical method, the error in the MSU inferred global temperature trend resulting from orbital drifts and residual inter-satellite differences of all satellites is estimated to be 0.06 K decade. Incorporating this error, our analysis shows that the global temperature increased at a rate of 0.13 +/- 0.06 K decade during 1980-97.

Global Warming: Evidence from Satellite Observations

NASA Technical Reports Server (NTRS)

Prabhakara, C.; Iacovazzi, R., Jr.; Yoo, J.-M.

2001-01-01

Observations made in Channel 2 (53.74 GHz) of the Microwave Sounding Unit (MSU) radiometer, flown on-board sequential, sun-synchronous, polar orbiting NOAA operational satellites, indicate that the mean temperature of the atmosphere over the globe increased during the period 1980 to 1999. In this study we have minimized systematic errors in the time series introduced by the satellite orbital drift in an objective manner. This is done with the help the onboard warm black body temperature, which is used in the calibration of the MSU radiometer. The corrected MSU Channel 2 observations of the NOAA satellite series reveal that the vertically weighted global mean temperature of the atmosphere, with a peak weight near the mid-troposphere, warmed at the rate of 0.13 K per decade (with an uncertainty of 0.05 K per decade) during 1980 to 1999. The global warming deduced from conventional meteorological data that have been corrected for urbanization effects agrees reasonably with this satellite deuced result.

Variability in daily, zonal mean lower-stratospheric temperatures

NASA Technical Reports Server (NTRS)

Christy, John R.; Drouilhet, S. James, Jr.

1994-01-01

Satellite data from the microwave sounding unit (MSU) channel 4, when carefully merged, provide daily zonal anomalies of lower-stratosphere temperature with a level of precision between 0.01 and 0.08 C per 2.5 deg latitude band. Global averages of these daily zonal anomalies reveal the prominent warming events due to volcanic aerosol in 1982 (El Chichon) and 1991 (Mt. Pinatubo), which are on the order of 1 C. The quasibiennial oscillation (QBO) may be extracted from these zonal data by applying a spatial filter between 15 deg N and 15 deg S latitude, which resembles the meridional curvature. Previously published relationships between the QBO and the north polar stratospheric temperatures during northern winter are examined but were not found to be reproduced in the MSU4 data. Sudden stratospheric warmings in the north polar region are represented in the MSU4 data for latitudes poleward of 70 deg N. In the Southern Hemisphere, there appears to be a moderate relationship between total ozone concentration and MSU4 temperatures, though it has been less apparent in 1991 and 1992. In terms of empirical modes of variability, the authors find a strong tendency in EOF 1 (39.2% of the variance) for anomalies in the Northern Hemisphere polar regions to be counterbalanced by anomalies equatorward of 40 deg N and 40 deg S latitudes. In addition, most of the modes revealed significant power in the 15-20 day period band.

Mississippi State University Center for Air Sea Technology FY95 Research Program

NASA Technical Reports Server (NTRS)

Yeske, Lanny; Corbin, James H.

1995-01-01

The Mississippi State University (MSU) Center for Air Sea Technology (CAST) evolved from the Institute for Naval Oceanography's (INO) Experimental Center for Mesoscale Ocean Prediction (ECMOP) which was started in 1989. MSU CAST subsequently began operation on 1 October 1992 under an Office of Naval Research (ONR) two-year grant which ended on 30 September 1994. In FY95 MSU CAST was successful in obtaining five additional research grants from ONR, as well as several other research contracts from the Naval Oceanographic Office via NASA, the Naval Research Laboratory, the Army Corps of Engineers, and private industry. In the past, MSU CAST technical research and development has produced tools, systems, techniques, and procedures that improve efficiency and overcome deficiency for both the operational and research communities residing with the Department of Defense, private industry, and university ocean modeling community. We continued this effort with the following thrust areas: to develop advanced methodologies and tools for model evaluation, validation and visualization, both oceanographic and atmospheric; to develop a system-level capability for conducting temporally and ; spatially scaled ocean simulations driven by or are responsive to ocean models, and take into consideration coupling to atmospheric models; to continue the existing oceanographic/atmospheric data management task with emphasis on distributed databases in a network environment, with database optimization and standardization, including use of Mosaic and World Wide Web (WWW) access; and to implement a high performance parallel computing technology for CAST ocean models

GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

PubMed Central

Nakayama, Akiyoshi; Nakaoka, Hirofumi; Yamamoto, Ken; Sakiyama, Masayuki; Shaukat, Amara; Toyoda, Yu; Okada, Yukinori; Kamatani, Yoichiro; Nakamura, Takahiro; Takada, Tappei; Inoue, Katsuhisa; Yasujima, Tomoya; Yuasa, Hiroaki; Shirahama, Yuko; Nakashima, Hiroshi; Shimizu, Seiko; Higashino, Toshihide; Kawamura, Yusuke; Ogata, Hiraku; Kawaguchi, Makoto; Ohkawa, Yasuyuki; Danjoh, Inaho; Tokumasu, Atsumi; Ooyama, Keiko; Ito, Toshimitsu; Kondo, Takaaki; Wakai, Kenji; Stiburkova, Blanka; Pavelka, Karel; Stamp, Lisa K; Dalbeth, Nicola; Sakurai, Yutaka; Suzuki, Hiroshi; Hosoyamada, Makoto; Fujimori, Shin; Yokoo, Takashi; Hosoya, Tatsuo; Inoue, Ituro; Takahashi, Atsushi; Kubo, Michiaki; Ooyama, Hiroshi; Shimizu, Toru; Ichida, Kimiyoshi; Shinomiya, Nariyoshi; Merriman, Tony R; Matsuo, Hirotaka

2017-01-01

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. Results In addition to the five loci we reported previously, further susceptibility loci were identified at a genome-wide significance level (p<5.0×10−8): urate transporter genes (SLC22A12 and SLC17A1) and HIST1H2BF-HIST1H4E for all gout cases, and NIPAL1 and FAM35A for the renal underexcretion gout subtype. While NIPAL1 encodes a magnesium transporter, functional analysis did not detect urate transport via NIPAL1, suggesting an indirect association with urate handling. Localisation analysis in the human kidney revealed expression of NIPAL1 and FAM35A mainly in the distal tubules, which suggests the involvement of the distal nephron in urate handling in humans. Clinically ascertained male patients with gout and controls of Caucasian and Polynesian ancestries were also genotyped, and FAM35A was associated with gout in all cases. A meta-analysis of the three populations revealed FAM35A to be associated with gout at a genome-wide level of significance (pmeta=3.58×10−8). Conclusions Our findings including novel gout risk loci provide further understanding of the molecular pathogenesis of gout and lead to a novel concept for the therapeutic target of gout/hyperuricaemia. PMID:27899376

Fructose malabsorption in people with and without gout: A case-control study.

PubMed

Batt, Caitlin; Fanning, Niamh; Drake, Jill; Frampton, Christopher; Gearry, Richard B; Stamp, Lisa K

2017-10-01

Higher fructose intake has been associated with hyperuricaemia and gout. Some individuals malabsorb fructose in the small intestine. The aims of this study were to determine the rate of fructose malabsorption and the effects of gout and fructose malabsorption on serum urate in people with and without gout. A total of 100 people with gout (cases) were age and gender matched with one control without gout. After a low fructose diet, fructose malabsorption was measured using a hydrogen and methane breath test with a 35g fructose load. In a subgroup of 35 cases and 35 controls, serum urate response to the fructose load over 240 minutes was measured. There was no significant difference in the rate of fructose malabsorption between cases and controls (48% vs. 52%; p = 0.67). Cases had a significantly lower mean (SEM) serum urate cumulative incremental concentration from baseline-240 minutes (iAUC 0-240 ) compared to controls 0.97 (0.56) vs. 4.78 (0.55); p < 0.001. C max was significantly lower in cases compared to controls [0.38 (0.003) vs. 0.40 (0.003); p < 0.001]. 95% of cases were receiving allopurinol. There was no significant difference between iAUC 0-240 or C max for malabsorbers compared to normal absorbers irrespective of case-control status. The mean (SEM) increase in serum urate between baseline and 30 minutes was 0.04 (0.004)mmol/l in the controls compared to 0.009 (0.002) in the cases (p < 0.001). The rates of fructose malabsorption are similar in people with and without gout. Allopurinol inhibits the increase in serum urate induced by a fructose load suggesting that people with gout receiving allopurinol may not need to restrict dietary intake of fructose. Copyright © 2017 Elsevier Inc. All rights reserved.

The Dietary Fructose:Vitamin C Intake Ratio Is Associated with Hyperuricemia in African-American Adults.

PubMed

Zheng, Zihe; Harman, Jane L; Coresh, Josef; Köttgen, Anna; McAdams-DeMarco, Mara A; Correa, Adolfo; Young, Bessie A; Katz, Ronit; Rebholz, Casey M

2018-03-01

A high fructose intake has been shown to be associated with increased serum urate concentration, whereas ascorbate (vitamin C) may lower serum urate by competing with urate for renal reabsorption. We assessed the combined association, as the fructose:vitamin C intake ratio, and the separate associations of dietary fructose and vitamin C intakes on prevalent hyperuricemia. We conducted cross-sectional analyses of dietary intakes of fructose and vitamin C and serum urate concentrations among Jackson Heart Study participants, a cohort of African Americans in Jackson, Mississippi, aged 21-91 y. In the analytic sample (n = 4576), multivariable logistic regression was used to examine the separate associations of dietary intakes of fructose and vitamin C and the fructose:vitamin C intake ratio with prevalent hyperuricemia (serum urate ≥7 mg/dL), after adjusting for age, sex, smoking, waist circumference, systolic blood pressure, estimated glomerular filtration rate, diuretic medication use, vitamin C supplement use, total energy intake, alcohol consumption, and dietary intake of animal protein. Analyses for individual dietary factors (vitamin C, fructose) were adjusted for the other dietary factor. In the fully adjusted model, there were 17% greater odds of hyperuricemia associated with a doubling of the fructose:vitamin C intake ratio (OR: 1.17; 95% CI: 1.08, 1.28), 20% greater odds associated with a doubling of fructose intake (OR: 1.20; 95% CI: 1.08, 1.34), and 13% lower odds associated with a doubling of vitamin C intake (OR: 0.87; 95% CI: 0.78, 0.97). Dietary fructose and the fructose:vitamin C intake ratio were more strongly associated with hyperuricemia among men than women (P-interaction ≤ 0.04). Dietary intakes of fructose and vitamin C are associated with prevalent hyperuricemia in a community-based population of African Americans.

Serum antioxidant and cholesterol levels in patients with different types of cancer.

PubMed

Abiaka, C; Al-Awadi, F; Al-Sayer, H; Gulshan, S; Behbehani, A; Farghally, M; Simbeye, A

2001-01-01

Serum antioxidant (urate, alpha-tocopherol) activity and cholesterol concentration in 142 patients of Indian and Arab (Kuwaitis and other Arabs) origin with different types of cancer (breast, colon, stomach, thyroid, oral, rectal, pancreatic, and renal) were compared to 100 age- and sex-matched control subjects. Values were expressed as medians (interquartile range). Urate concentration was significantly decreased in male patients compared to male controls (P < 0.0001) and in female patients and female breast cancer cases compared to female controls; P < 0.0001 and P = 0.001, respectively. Alpha-tocopherol concentration decreased significantly in total cancer, stomach, colon, rectal, and breast cancer cases than the controls; P < 0.0001, P < 0.0001, P < 0.0001, P = 0.012, and P = 0.022, respectively. Cholesterol concentration decreased significantly in stomach, oral, colon, and total cancer cases compared to the controls; P < 0.0001, P < 0.0001, P = 0.002, and P = 0.012, respectively. Among controls, females had significantly (P < 0.0001) lower concentrations of alpha-tocopherol than males. Among patients, cholesterol, urate, and alpha-tocopherol concentrations decreased significantly in smokers than in nonsmokers; P < 0.0001, P = 0.004, and P = 0.047, respectively. Generally, changes in alpha-tocopherol/cholesterol ratios mimicked changes in alpha-tocopherol concentration. Concentrations of all parameters decreased significantly in male patients compared to male controls. Age was positively associated with all three analytes with respect to the controls. Alpha-tocopherol correlated with cholesterol in cancer patients (r = 0.367; P < 0.0001) and with urate in the controls (r = 0.342; P < 0.0001). The data suggest cancer-related diminished synthesis of cholesterol and, generally, a greater antioxidant burden for alpha-tocopherol than urate in cancer-generated oxidative stress. The increased incidence of pancreatic cancer in Kuwaitis warrants further study. Copyright 2001 Wiley-Liss, Inc.

Secretion of S100A8, S100A9, and S100A12 by Neutrophils Involves Reactive Oxygen Species and Potassium Efflux.

PubMed

Tardif, Mélanie R; Chapeton-Montes, Julie Andrea; Posvandzic, Alma; Pagé, Nathalie; Gilbert, Caroline; Tessier, Philippe A

2015-01-01

S100A8/A9 (calprotectin) and S100A12 proinflammatory mediators are found at inflammatory sites and in the serum of patients with inflammatory or autoimmune diseases. These cytoplasmic proteins are secreted by neutrophils at sites of inflammation via alternative secretion pathways of which little is known. This study examined the nature of the stimuli leading to S100A8/A9 and S100A12 secretion as well as the mechanism involved in this alternative secretion pathway. Chemotactic agents, cytokines, and particulate molecules were used to stimulate human neutrophils. MSU crystals, PMA, and H2O2 induced the release of S100A8, S100A9, and S100A12 homodimers, as well as S100A8/A9 heterodimer. High concentrations of S100A8/A9 and S100A12 were secreted in response to nanoparticles like MSU, silica, TiO2, fullerene, and single-wall carbon nanotubes as well as in response to microbe-derived molecules, such as zymosan or HKCA. However, neutrophils exposed to the chemotactic factors fMLP failed to secrete S100A8/A9 or S100A12. Secretion of S100A8/A9 was dependent on the production of reactive oxygen species and required K(+) exchanges through the ATP-sensitive K(+) channel. Altogether, these findings suggest that S100A12 and S100A8/A9 are secreted independently either via distinct mechanisms of secretion or following the activation of different signal transduction pathways.

Secretion of S100A8, S100A9, and S100A12 by Neutrophils Involves Reactive Oxygen Species and Potassium Efflux

PubMed Central

Tardif, Mélanie R.; Chapeton-Montes, Julie Andrea; Posvandzic, Alma; Pagé, Nathalie; Gilbert, Caroline; Tessier, Philippe A.

2015-01-01

S100A8/A9 (calprotectin) and S100A12 proinflammatory mediators are found at inflammatory sites and in the serum of patients with inflammatory or autoimmune diseases. These cytoplasmic proteins are secreted by neutrophils at sites of inflammation via alternative secretion pathways of which little is known. This study examined the nature of the stimuli leading to S100A8/A9 and S100A12 secretion as well as the mechanism involved in this alternative secretion pathway. Chemotactic agents, cytokines, and particulate molecules were used to stimulate human neutrophils. MSU crystals, PMA, and H2O2 induced the release of S100A8, S100A9, and S100A12 homodimers, as well as S100A8/A9 heterodimer. High concentrations of S100A8/A9 and S100A12 were secreted in response to nanoparticles like MSU, silica, TiO2, fullerene, and single-wall carbon nanotubes as well as in response to microbe-derived molecules, such as zymosan or HKCA. However, neutrophils exposed to the chemotactic factors fMLP failed to secrete S100A8/A9 or S100A12. Secretion of S100A8/A9 was dependent on the production of reactive oxygen species and required K+ exchanges through the ATP-sensitive K+ channel. Altogether, these findings suggest that S100A12 and S100A8/A9 are secreted independently either via distinct mechanisms of secretion or following the activation of different signal transduction pathways. PMID:27057553

Potential Pharmacologic Treatments for Cystinuria and for Calcium Stones Associated with Hyperuricosuria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goldfarb, David S.

Two new potential pharmacologic therapies for recurrent stone disease are described. The role of hyperuricosuria in promoting calcium stones is controversial with only some but not all epidemiologic studies demonstrating associations between increasing urinary uric acid excretion and calcium stone disease. The relationship is supported by the ability of uric acid to 'salt out' (or reduce the solubility of) calcium oxalate in vitro. A randomized, controlled trial of allopurinol in patients with hyperuricosuria and normocalciuria was also effective in preventing recurrent stones. Febuxostat, a nonpurine inhibitor of xanthine oxidase (also known as xanthine dehydrogenase or xanthine oxidoreductase) may have advantagesmore » over allopurinol and is being tested in a similar protocol, with the eventual goal of determining whether urate-lowering therapy prevents recurrent calcium stones. Treatments for cystinuria have advanced little in the past 30 years. Atomic force microscopy has been used recently to demonstrate that effective inhibition of cystine crystal growth is accomplished at low concentrations of L-cystine methyl ester and L-cystine dimethyl ester, structural analogs of cystine that provide steric inhibition of crystal growth. In vitro, L-cystine dimethyl ester had a significant inhibitory effect on crystal growth. The drug's safety and effectiveness will be tested in an Slc3a1 knockout mouse that serves as an animal model of cystinuria.« less

Elevated synovial fluid concentration of adenosine triphosphate in dogs with osteoarthritis or sodium urate-induced synovitis of the stifle.

PubMed

Torres, Bryan T; Jimenez, David A; Budsberg, Steven C

2016-07-19

Adenosine triphosphate has been shown to stimulate nociceptive nerve terminals in joints. Elevated synovial fluid adenosine triphosphate concentrations as well as a correlation between synovial fluid adenosine triphosphate concentrations and osteoarthritic knee pain has been demonstrated in humans, but not yet in dogs. This study documented elevated synovial fluid adenosine triphosphate concentrations in the stifles of dogs with secondary osteoarthritis and urate-induced synovitis, as compared to normal stifles.

Local and systemic oxidant/antioxidant status before and during lung cancer radiotherapy

PubMed Central

Crohns, Marika; Saarelainen, Seppo; Kankaanranta, Hannu; Moilanen, Eeva; Alho, Hannu; Kellokumpu-Lehtinen, Pirkko

2009-01-01

To examine local and systemic oxidative status of lung cancer (LC) and oxidant effects of radiotherapy (RT), this study evaluated antioxidants and markers of oxidative and nitrosative stress in bronchoalveolar lavage (BAL) fluid and in the blood of 36 LC patients and 36 non-cancer controls at baseline and during and after RT for LC. LC patients had higher baseline serum urate, plasma nitrite and lower serum oxidized proteins than controls (p = 0.016, p < 0.001 and p = 0.027, respectively), but BAL fluid oxidative stress markers were similar. RT tended to raise some antioxidants, however, significant increases were seen in serum urate, conjugated dienes and TBARS (p = 0.044, p = 0.034 and p = 0.004, respectively) 3 months after RT. High urate at baseline may compensate against the oxidative stress caused by LC. RT shifts the oxidant/antioxidant balance towards lipid peroxidation, although the antioxidant defense mechanisms of the body appear to counteract the increased oxidative stress rather effectively. PMID:19444690

The genetics of gout: towards personalised medicine?

PubMed

Dalbeth, Nicola; Stamp, Lisa K; Merriman, Tony R

2017-05-31

Over the last decade, there have been major advances in the understanding of the genetic basis of hyperuricaemia and gout as well as of the pharmacogenetics of urate-lowering therapy. Key findings include the reporting of 28 urate-associated loci, the discovery that ABCG2 plays a central role on extra-renal uric acid excretion, the identification of genes associated with development of gout in the context of hyperuricaemia, recognition that ABCG2 variants influence allopurinol response, and the impact of HLA-B*5801 testing in reducing the prevalence of allopurinol hypersensitivity in high-risk populations. These advances, together with the reducing cost of whole genome sequencing, mean that integrated personalised medicine approaches may soon be possible in clinical practice. Genetic data may inform assessment of disease prognosis in individuals with hyperuricaemia or established gout, personalised lifestyle advice, selection and dosing of urate-lowering therapy, and prevention of serious medication adverse effects. In this article, we summarise the discoveries from genome-wide association studies and discuss the potential for translation of these findings into clinical practice.

Uric Acid Spherulites in the Reflector Layer of Firefly Light Organ

PubMed Central

Goh, King-Siang; Sheu, Hwo-Shuenn; Hua, Tzu-En; Kang, Mei-Hua; Li, Chia-Wei

2013-01-01

Background In firefly light organs, reflector layer is a specialized tissue which is believed to play a key role for increasing the bioluminescence intensity through reflection. However, the nature of this unique tissue remains elusive. In this report, we investigated the role, fine structure and nature of the reflector layer in the light organ of adult Luciola cerata. Principal Findings Our results indicated that the reflector layer is capable of reflecting bioluminescence, and contains abundant uric acid. Electron microscopy (EM) demonstrated that the cytosol of the reflector layer's cells is filled with densely packed spherical granules, which should be the uric acid granules. These granules are highly regular in size (∼700 nm in diameter), and exhibit a radial internal structure. X-ray diffraction (XRD) analyses revealed that an intense single peak pattern with a d-spacing value of 0.320 nm is specifically detected in the light organ, and is highly similar to the diffraction peak pattern and d-spacing value of needle-formed crystals of monosodium urate monohydrate. However, the molar ratio evaluation of uric acid to various cations (K+, Na+, Ca2+ and Mg2+) in the light organ deduced that only a few uric acid molecules were in the form of urate salts. Thus, non-salt uric acid should be the source of the diffraction signal detected in the light organ. Conclusions In the light organ, the intense single peak diffraction signal might come from a unique needle-like uric acid form, which is different from other known structures of non-salt uric acid form. The finding of a radial structure in the granules of reflector layer implies that the spherical uric acid granules might be formed by the radial arrangement of needle-formed packing matter. PMID:23441187

The hURAT1 rs559946 polymorphism and the incidence of gout in Han Chinese men.

PubMed

Li, C; Yu, Q; Han, L; Wang, C; Chu, N; Liu, S

2014-01-01

Our previous study identified rs559946, a human urate transporter 1 (hURAT1) single nucleotide polymorphism (SNP), as being significantly associated with risk of primary hyperuricaemia (HUA) in a Han Chinese population. In the current study we aimed to identify the genetic effects of rs559946 on gout susceptibility in Han Chinese men. A total of 335 patients with gout and 376 healthy controls were recruited for a case-control association study. To examine the functional effect of rs559946, we performed luciferase reporter assays and an electrophoretic mobility shift assay (EMSA). rs559946 was found to be significantly associated with gout susceptibility (p = 0.004), with T-allele carriers showing a decreased risk of gout [odds ratio (OR) 0.70, 95% confidence interval (CI) 0.55-0.89]. Multiple linear regression analysis identified a significant association between rs559946 genotypes and tophi. Luciferase reporter assays show increased transcriptional activity of the hURAT1 promoter with the C allele of rs559946. EMSA detected binding of nuclear proteins to both the T and C alleles, although increased binding was observed with the T allele. Cold competition assays suggest that rs559946 may bind within a glucocorticoid receptor (GR) binding motif. Our study suggests that the rs559946 polymorphism is associated with increased HUA risk and may also contribute to gout development in Han Chinese men. The T to C substitution within rs559946 increased the transcriptional activity, and potentially increases gout susceptibility.

New and Pipeline Drugs for Gout.

PubMed

Keenan, Robert T; Schlesinger, Naomi

2016-06-01

Gout is the most common inflammatory arthropathy in the western world. Affecting millions and accounting for lost wages, increased health care costs, and significant disability, it remains a burden for those afflicted, their families, and the health care system. Despite the availability of a number of effective therapies, gout is often inadequately treated, and its impact on the patients overall health and well-being is underestimated by physicians and patients alike. For many decades, controlling acute flares was the priority in the management of gout. More recently, however, a deeper understanding of gout pathophysiology has resulted in a new appreciation that gout impacts the patient with consequences well beyond the episodes of acute inflammatory arthritis. Reflecting the chronic nature of the disease, gout treatment needs to be chronic as well, and aimed at reducing the underlying cause of gout-hyperuricemia-as well as the symptom of acute attacks. Therapy therefore requires both urate lowering and anti-inflammatory strategies. Unfortunately, the most commonly used urate lowering and anti-inflammatory treatments may be problematic in some gout patients, who often have multiple comorbidities that establish relative contraindications. Novel urate lowering therapies, and new medications to treat and prevent acute gouty flares, can not only improve care of the individual; they can also lead to a better discourse for the edification of those who manage and are managed for this underestimated disease. In this paper, we discuss new and pipeline drugs for acute gout, prophylactic anti-inflammatory therapies as well as urate lowering therapies.

Iron catalyzed conversion of NO into nitrosonium (NO+) and nitroxyl (HNO/NO-) species.

PubMed

Stojanović, Srdjan; Stanić, Dragana; Nikolić, Milan; Spasić, Mihailo; Niketić, Vesna

2004-11-01

The conversion of NO into its congeners, nitrosonium (NO+) and nitroxyl (HNO/NO-) species, has important consequences in NO metabolism. Dinitrosyl iron complex (DNIC) combined with thiol ligands was shown to catalyze the conversion of NO into NO+, resulting in the synthesis of S-nitrosothiols (RSNO) both in vitro and in vivo. The formation mechanism of DNIC was proposed to involve the intermediate release of nitroxyl. Since the detection of hydroxylamine (as the product of a rapid reaction of HNO/NO- with thiols) is taken as the evidence for nitroxyl generation, we examined the formation of hydroxylamine, RSNO, and nitrite (the product of a rapid reaction of NO+ with water) in neutral solutions containing iron ions and thiols exposed to NO under anaerobic conditions. Hydroxylamine was detected in NO treated solutions of iron ions in the presence of cysteine, but not glutathione (GSH). The addition of urate, a major "free" iron-binding agent in humans, to solutions of GSH and iron ions, and the subsequent treatment of these solutions with NO increased the synthesis of GSNO and resulted in the formation of hydroxylamine. This caused a loss of urate and yielded a novel nitrosative/nitration product. GSH attenuated the urate decomposition to such a degree that it could be reflected as the function of GSH:urate. Results described here contribute to the understanding of the role of iron ions in catalyzing the conversion of NO into HNO/NO- and point to the role of uric acid not previously described.

Risk factors for incident hyperuricemia during mid-adulthood in African American and White men and women enrolled in the ARIC cohort study

PubMed Central

2013-01-01

Background Increased serum urate levels are associated with poor outcomes including but not limited to gout. It is unclear whether serum urate levels are the sole predictor of incident hyperuricemia or whether demographic and clinical risk factors also predict the development of hyperuricemia. The goal of this study was to identify risk factors for incident hyperuricemia over 9 years in a population-based study, ARIC. Methods ARIC recruited individuals from 4 US communities; 8,342 participants who had urate levels <7.0 mg/dL were included in this analysis. Risk factors (including baseline, 3-year, and change in urate level over 3 years) for 9-year incident hyperuricemia (urate level of >7.0 g/dL) were identified using an AIC-based selection approach in a modified Poisson regression model. Results The 9-year cumulative incidence of hyperuricemia was 4%; men = 5%; women = 3%; African Americans = 6% and whites = 3%. The adjusted model included 9 predictors for incident hyperuricemia over 9 years: male sex (RR = 1.73 95% CI: 1.36-2.21), African-American race (RR = 1.79 95% CI: 1.37-2.33), smoking (RR = 1.27, 95% CI: 0.97-1.67),

The First U.S. Naval Observatory Robotic Astrometric Telescope Catalog

DTIC Science & Technology

2015-10-01

in the “info” folder. URAT1 covers almost the entire northern sky and most of the area δ �−15°, plus the far south area around Pluto . 2.3. Robotic...meeting acceptable quality standards. A total of 14 and 12 exposures of the Pluto field area taken on 2013 September 19 and 2014 September 06...for our project. 2MASS was used for near-IR photometry and as the first epoch of URAT1 proper motions. Bill Gray (Project Pluto ) is thanked for making

Development of a COTS Mass Storage Unit for the Space Readiness Coherent Lidar Experiment

NASA Technical Reports Server (NTRS)

Liggin, Karl; Clark, Porter

1999-01-01

The technology to develop a Mass Storage Unit (MSU) using commercial-off-the-shelf (COTS) hard drives is an on-going challenge to meet the Space Readiness Coherent Lidar Experiment (SPARCLE) program requirements. A conceptual view of SPARCLE's laser collecting atmospheric data from the shuttle is shown in Figure 1. The determination to develop this technology required several in depth studies before an actual COTS hard drive was selected to continue this effort. Continuing the development of the MSU can, and will, serve future NASA programs that require larger data storage and more on-board processing.

GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes.

PubMed

Nakayama, Akiyoshi; Nakaoka, Hirofumi; Yamamoto, Ken; Sakiyama, Masayuki; Shaukat, Amara; Toyoda, Yu; Okada, Yukinori; Kamatani, Yoichiro; Nakamura, Takahiro; Takada, Tappei; Inoue, Katsuhisa; Yasujima, Tomoya; Yuasa, Hiroaki; Shirahama, Yuko; Nakashima, Hiroshi; Shimizu, Seiko; Higashino, Toshihide; Kawamura, Yusuke; Ogata, Hiraku; Kawaguchi, Makoto; Ohkawa, Yasuyuki; Danjoh, Inaho; Tokumasu, Atsumi; Ooyama, Keiko; Ito, Toshimitsu; Kondo, Takaaki; Wakai, Kenji; Stiburkova, Blanka; Pavelka, Karel; Stamp, Lisa K; Dalbeth, Nicola; Sakurai, Yutaka; Suzuki, Hiroshi; Hosoyamada, Makoto; Fujimori, Shin; Yokoo, Takashi; Hosoya, Tatsuo; Inoue, Ituro; Takahashi, Atsushi; Kubo, Michiaki; Ooyama, Hiroshi; Shimizu, Toru; Ichida, Kimiyoshi; Shinomiya, Nariyoshi; Merriman, Tony R; Matsuo, Hirotaka

2017-05-01

A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. 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. In addition to the five loci we reported previously, further susceptibility loci were identified at a genome-wide significance level (p<5.0×10 -8 ): urate transporter genes ( SLC22A12 and SLC17A1 ) and HIST1H2BF-HIST1H4E for all gout cases, and NIPAL1 and FAM35A for the renal underexcretion gout subtype. While NIPAL1 encodes a magnesium transporter, functional analysis did not detect urate transport via NIPAL1, suggesting an indirect association with urate handling. Localisation analysis in the human kidney revealed expression of NIPAL1 and FAM35A mainly in the distal tubules, which suggests the involvement of the distal nephron in urate handling in humans. Clinically ascertained male patients with gout and controls of Caucasian and Polynesian ancestries were also genotyped, and FAM35A was associated with gout in all cases. A meta-analysis of the three populations revealed FAM35A to be associated with gout at a genome-wide level of significance (p meta =3.58×10 -8 ). Our findings including novel gout risk loci provide further understanding of the molecular pathogenesis of gout and lead to a novel concept for the therapeutic target of gout/hyperuricaemia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Effect and mechanism of dioscin from Dioscorea spongiosa on uric acid excretion in animal model of hyperuricemia.

PubMed

Zhang, Yi; Jin, Lijun; Liu, Jinchang; Wang, Wei; Yu, Haiyang; Li, Jian; Chen, Qian; Wang, Tao

2018-03-25

Dioscin, a spirostane glycoside, the rhizoma of Dioscorea septemloba (Diocoreacea) is used for diuresis, rheumatism, and joints pain. Given the poor solubility and stability of Dioscin, we proposed a hypothesis that Dioscin's metabolite(s) are the active substance(s) in vivo to contribute to the reducing effects on serum uric acid levels. The aim of this study is to identify the active metabolite(s) of Dioscin in vivo and to explore the mechanism of its antihyperuricemic activity. After oral administration of Dioscin in potassium oxonate (PO) induced hyperuricemia rats and adenine-PO induced hyperuricemia mice models, serum uric acid and creatinine levels, clearance of uric acid and creatinine, fractional excretion of uric acid, and renal pathological lesions were determined were used to evaluate the antihyperuricemic effects. Renal glucose transporter-9 (GLUT-9) and organic anion transporter-1 (OAT-1) expressions were analyzed by western blotting method. Renal uric acid excretion was evaluated using stably urate transporter-1 (URAT-1) transfected human epithelial kidney cell line. Intestinal uric acid excretion was evaluated by measuring the transcellular transport of uric acid in HCT116 cells. In hyperuricemia rats, both 25 and 50mg/kg of oral Dioscin decreased serum uric acid levels over 4h. In the hyperuricemia mice, two weeks treatment of Dioscin significantly decreased serum uric acid and creatinine levels, increased clearance of uric acid and creatinine, increased fractional excretion of uric acid, and reduced renal pathological lesions caused by hyperuricemia. In addition, renal GLUT -9 was significantly down-regulated and OAT-1 was up-regulated in Dioscin treated hyperuricemia mice. Dioscin's metabolite Tigogenin significantly inhibited uric acid re-absorption via URAT1 from 10 to 100μM. Diosgenin and Tigogenin increased uric acid excretion via ATP binding cassette subfamily G member 2 (ABCG2). Decreasing effect of Dioscin on serum uric acid level and enhancing effect on urate excretion were confirmed in hyperuricemia animal models. Tigogenin, a metabolite of Dioscin, was identified as an active substance with antihyperuricemic activity in vivo, through inhibition of URAT1 and promotion of ABCG2. Copyright © 2017 Elsevier B.V. All rights reserved.

Gout and Metabolic Syndrome: a Tangled Web.

PubMed

Thottam, Gabrielle E; Krasnokutsky, Svetlana; Pillinger, Michael H

2017-08-26

The complexity of gout continues to unravel with each new investigation. Gout sits at the intersection of multiple intrinsically complex processes, and its prevalence, impact on healthcare costs, and association with important co-morbidities make it increasingly relevant. The association between gout and type 2 diabetes, hypertension, hyperlipidemia, cardiovascular disease, renal disease, and obesity suggest that either gout, or its necessary precursor hyperuricemia, may play an important role in the manifestations of the metabolic syndrome. In this review, we analyze the complex interconnections between gout and metabolic syndrome, by reviewing gout's physiologic and epidemiologic relationships with its major co-morbidities. Increasing evidence supports gout's association with metabolic syndrome. More specifically, both human studies and animal models suggest that hyperuricemia may play a role in promoting inflammation, hypertension and cardiovascular disease, adipogenesis and lipogenesis, insulin and glucose dysregulation, and liver disease. Fructose ingestion is associated with increased rates of hypertension, weight gain, impaired glucose tolerance, and dyslipidemia and is a key driver of urate biosynthesis. AMP kinase (AMPK) is a central regulator of processes that tend to mitigate against the metabolic syndrome. Within hepatocytes, leukocytes, and other cells, a fructose/urate metabolic loop drives key inhibitors of AMPK, including AMP deaminase and fructokinase, that may tilt the balance toward metabolic syndrome progression. Preliminary evidence suggests that agents that block the intracellular synthesis of urate may restore AMPK activity and help maintain metabolic homeostasis. Gout is both an inflammatory and a metabolic disease. With further investigation of urate's role, the possibility of proper gout management additionally mitigating metabolic syndrome is an evolving and important question.

Evaluation of dogs with genetic hyperuricosuria and urate urolithiasis consuming a purine restricted diet: a pilot study.

PubMed

Westropp, Jodi L; Larsen, Jennifer A; Johnson, Eric G; Bannasch, Dannika; Fascetti, Andrea J; Biourge, Vincent; Queau, Yann

2017-02-08

Urate urolithiasis is a common problem in breed homozygous for the mutation that results in hyperuricosuria. Low purine diets have been recommended to reduce purine intake in these dogs. A higher protein, purine restricted diet with water added was evaluated in dogs with genetic hyperuricosuria and a history of clinical urate urolithiasis over a one year time period. Dogs were evaluated at baseline and 2, 6, and 12 months after initiating the test diet. Bloodwork, urinalysis, abdominal ultrasound, body composition, and 24-h urinary purine metabolite analyses were performed. Transient, mild, self-limited lower urinary tract signs were noted in only one dog on a single day, despite variable but usually mild and occasionally moderate amounts of echogenic bladder stones (<2-3 mm in size) in almost every dog at each visit. No significant differences were noted in urine specific gravity, urine pH, lean body condition score or body composition. Urinary uric acid concentration was lower on the test diet (p = 0.008), but 24-h uric acid excretions were similar (p = 0.220) compared to baseline. Significant differences between least squares mean plasma amino acid concentrations measured at the 0 and 12-month visits were found only for valine (p = 0.0119) and leucine (p = 0.0017). This study suggests the use of a low purine, higher protein diet with added water may be beneficial as part of the management of dogs with genetic hyperuricosuria and history of clinical urate urolithiasis.

The dual actions of morin (3,5,7,2',4'-pentahydroxyflavone) as a hypouricemic agent: uricosuric effect and xanthine oxidase inhibitory activity.

PubMed

Yu, Zhifeng; Fong, Wing Ping; Cheng, Christopher H K

2006-01-01

Hyperuricemia is associated with a number of pathological conditions such as gout. Lowering of elevated uric acid level in the blood could be achieved by xanthine oxidase inhibitors and inhibitors of renal urate reabsorption. Some natural compounds isolated from herbs used in traditional Chinese medicine have been previously demonstrated to possess xanthine oxidase inhibitory activities. In the present investigation, morin (3,5,7,2',4'-pentahydroxyflavone), which occurs in the twigs of Morus alba L. documented in traditional Chinese medicinal literature to treat conditions akin to gout, was demonstrated to exert potent inhibitory action on urate uptake in rat renal brush-border membrane vesicles, indicating that this compound acts on the kidney to inhibit urate reabsorption. Lineweaver-Burk transformation of the inhibition kinetics data demonstrated that the inhibition of urate uptake was of a competitive type, with a K(i) value of 17.4 microM. In addition, morin was also demonstrated to be an inhibitor of xanthine oxidase. Lineweaver-Burk analysis of the enzyme kinetics indicated that the mode of inhibition was of a mixed type, with K(i) and K(ies) values being 7.9 and 35.1 microM, respectively. Using an oxonate-induced hyperuricemic rat model, morin was indeed shown to exhibit an in vivo uricosuric action, which could explain, in part at least, the observed hypouricemic effect of morin in these rats. The potential application of this compound in the treatment of conditions associated with hyperuricemia was discussed.

Calcium supplementation during pregnancy for preventing hypertensive disorders is not associated with changes in platelet count, urate, and urinary protein: a randomized control trial.

PubMed

Hofmeyr, G J; Mlokoti, Z; Nikodem, V C; Mangesi, L; Ferreira, S; Singata, M; Jafta, Z; Merialdi, M; Hazelden, C; Villar, J

2008-01-01

To test the hypothesis that calcium supplementation inhibits the underlying pathological processes in women with preeclampsia. Seven hundred and eight nulliparous women were enrolled in a WHO randomized double-blind trial, who received 1.5 g of calcium or placebo from 20 weeks of pregnancy or earlier. Platelet count, serum urate, and urinary protein/creatinine ratio were measured at or near 35 gestational weeks. No difference was detected in rates of abnormal platelet count (relative risk [RR] 1.18; 95% confidence interval [CI], 0.63 to 2.18), serum urate level (1.0; 0.64 to 1.57) or urine protein/creatinine ratio (1.01; 0.76 to 1.34). This was consistent with the main trial finding of no difference in the incidence of 'dipstick' proteinuria between women receiving calcium and those receiving placebo (8312 women; RR, 1.01; 95% CI, 0.88 to 1.15). An effect of calcium supplementation in the second half of pregnancy on the rate of abnormal laboratory measures associated with preeclampsia was not demonstrated.

Space Radiation Monitoring Center at SINP MSU

NASA Astrophysics Data System (ADS)

Kalegaev, Vladimir; Barinova, Wera; Barinov, Oleg; Bobrovnikov, Sergey; Dolenko, Sergey; Mukhametdinova, Ludmila; Myagkova, Irina; Nguen, Minh; Panasyuk, Mikhail; Shiroky, Vladimir; Shugay, Julia

2015-04-01

Data on energetic particle fluxes from Russian satellites have been collected in Space monitoring data center at Moscow State University in the near real-time mode. Web-portal http://smdc.sinp.msu.ru/ provides operational information on radiation state of the near-Earth space. Operational data are coming from space missions ELECTRO-L1, Meteor-M2. High-resolution data on energetic electron fluxes from MSU's satellite VERNOV with RELEC instrumentation on board are also available. Specific tools allow the visual representation of the satellite orbit in 3D space simultaneously with particle fluxes variations. Concurrent operational data coming from other spacecraft (ACE, GOES, SDO) and from the Earth's surface (geomagnetic indices) are used to represent geomagnetic and radiation state of near-Earth environment. Internet portal http://swx.sinp.msu.ru provides access to the actual data characterizing the level of solar activity, geomagnetic and radiation conditions in heliosphere and the Earth's magnetosphere in the real-time mode. Operational forecasting services automatically generate alerts on particle fluxes enhancements above the threshold values, both for SEP and relativistic electrons, using data from LEO and GEO orbits. The models of space environment working in autonomous mode are used to generalize the information obtained from different missions for the whole magnetosphere. On-line applications created on the base of these models provide short-term forecasting for SEP particles and relativistic electron fluxes at GEO and LEO, Dst and Kp indices online forecasting up to 1.5 hours ahead. Velocities of high-speed streams in solar wind on the Earth orbit are estimated with advance time of 3-4 days. Visualization system provides representation of experimental and modeling data in 2D and 3D.

Altered newborn gender distribution in patients with low mid-trimester maternal serum human chorionic gonadotropin (MShCG).

PubMed

Santolaya-Forgas, J; Meyer, W J; Burton, B K; Scommegna, A

1997-01-01

to determine if the sex ratio (male/female) is altered in infants born to patients with low mid-trimester maternal serum human chorionic gonadotropin (MShCG). Between 2/1/90 and 1/3/91, 3,116 patients underwent prenatal screening using second-trimester maternal serum alpha-fetoprotein (MSAFP), MShCG, and maternal serum unconjugated estriol (MSuE3). Among these, there were 132 patients with low second-trimester MShCG (< 0.4 MoM), normal MSAFP and MSuE3. The gender distribution of these term, normal newborns was compared to that of 237 controls, matched for race, maternal age, and referral source and delivered at term to mothers with normal mid-trimester MSAFP, MSuE3, and MShCG. The gender distribution of these two groups of newborns was also compared to that of 78 term newborns from the same obstetrical population delivered to mothers with second-trimester MShCG > 2.5 MoM and normal MSAFP and MSuE3. All patients had a complete obstetrical history. Forty-nine percent of the controls were male vs. 62% of the group with slow second-trimester MShCG (P < .01). Within the group with low MShCG, 59% of infants were male when the MShCG was between 0.19 and 0.4 MoM (A) and 80% when the MShCG was < 0.2 MoM (B) (control vs. A vs. B P < .005). The sex ratio in the high-MShCG group was similar to control. The data suggest that gender distribution is different from normal in patients with low mid-trimester MShCG.

Transcriptional Analysis of Resistance to Low Temperatures in Bermudagrass Crown Tissues

PubMed Central

Melmaiee, Kalpalatha; Anderson, Michael; Elavarthi, Sathya; Guenzi, Arron; Canaan, Patricia

2015-01-01

Bermudagrass (Cynodon dactylon L pers.) is one of the most geographically adapted and utilized of the warm-season grasses. However, bermudagrass adaptation to the Northern USA is limited by freeze damage and winterkill. Our study provides the first large-scale analyses of gene expression in bermudagrass regenerative crown tissues during cold acclimation. We compared gene expression patterns in crown tissues from highly cold tolerant “MSU” and susceptible “Zebra” genotypes exposed to near-freezing temperatures. Suppressive subtractive hybridization was used to isolate putative cold responsive genes Approximately, 3845 transcript sequences enriched for cold acclimation were deposited in the GenBank. A total of 4589 ESTs (3184 unigenes) including 744 ESTs associated with the bermudagrass disease spring dead spot were printed on microarrays and hybridized with cold acclimated complementary Deoxyribonucleic acid (cDNA). A total of 587 differentially expressed unigenes were identified in this study. Of these only 97 (17%) showed significant NCBI matches. The overall expression pattern revealed 40% more down- than up-regulated genes, which was particularly enhanced in MSU compared to Zebra. Among the up-regulated genes 68% were uniquely expressed in MSU (36%) or Zebra (32%). Among the down-regulated genes 40% were unique to MSU, while only 15% to Zebra. Overall expression intensity was significantly higher in MSU than in Zebra (p value ≤ 0.001) and the overall number of genes expressed at 28 days was 2.7 fold greater than at 2 days. These changes in expression patterns reflect the strong genotypic and temporal response to cold temperatures. Additionally, differentially expressed genes from this study can be utilized for developing molecular markers in bermudagrass and other warm season grasses for enhancing cold hardiness. PMID:26348040

Automated Transfer Vehicle (ATV) Critical Safety Software Overview

NASA Astrophysics Data System (ADS)

Berthelier, D.

2002-01-01

The European Automated Transfer Vehicle is an unmanned transportation system designed to dock to International Space Station (ISS) and to contribute to the logistic servicing of the ISS. Concisely, ATV control is realized by a nominal flight control function (using computers, softwares, sensors, actuators). In order to cover the extreme situations where this nominal chain can not ensure safe trajectory with respect to ISS, a segregated proximity flight safety function is activated, where unsafe free drift trajectories can be encountered. This function relies notably on a segregated computer, the Monitoring and Safing Unit (MSU) ; in case of major ATV malfunction detection, ATV is then controlled by MSU software. Therefore, this software is critical because a MSU software failure could result in catastrophic consequences. This paper provides an overview both of this software functions and of the software development and validation method which is specific considering its criticality. First part of the paper describes briefly the proximity flight safety chain. Second part deals with the software functions. Indeed, MSU software is in charge of monitoring nominal computers and ATV corridors, using its own navigation algorithms, and, if an abnormal situation is detected, it is in charge of the ATV control during the Collision Avoidance Manoeuvre (CAM) consisting in an attitude controlled braking boost, followed by a Post-CAM manoeuvre : a Sun-pointed ATV attitude control during up to 24 hours on a safe trajectory. Monitoring, navigation and control algorithms principles are presented. Third part of this paper describes the development and validation process : algorithms functional studies , ADA coding and unit validations ; algorithms ADA code integration and validation on a specific non real-time MATLAB/SIMULINK simulator ; global software functional engineering phase, architectural design, unit testing, integration and validation on target computer.

The Physics Department of Moscow University: In Its Ladies' Faces

NASA Astrophysics Data System (ADS)

Elena, Ermolaeva

2005-10-01

In commemoration of the 250th anniversary of Moscow University, the Women Council of MSU published a biographical dictionary dedicated to women who contributed significantly to the academic success of their institution and who distinguished themselves both in research and in teaching. The book contains brief biographies of some 619 women employed by MSU; 63 of these entries are for members of the Department of Physics and of its adjacent research institutes. They are doctors of sciences, full professors, recipients of government as well as university awards, and some are WWII veterans. Their lives in science have embodied all tendencies of the Soviet period of the country. The great majority graduated from Moscow State University and have been working at MSU for more than 25 years. At present, the Physics Department consists of 37 sectors with more than two hundred doctors of sciences, 15% of whom are women. The information supplied by the dictionary, combined with data on the younger staff of MSU with similar degrees in physics, lets us compare tendencies in women's professional development, their research and teaching careers, and their success in publishing. It also lets us see some of the key issues. Since 1933 (the year of establishment) more than 25,000 people have graduated from the Physics Department, a quarter of whom were girls. Of 90 students who have graduated with honors this year, one third were girls, and of 22 award-winning thesis this year, 10 were defended by them. About 400 persons are participating in the 3-year postgraduate program of the Physics Department; 30% of all students enrolled this year are girls. Half the winners of annual awards to students, postgraduate students, and ``young scientists'' in physics this year were girls. The percent of successful women in physics is growing.

Climate Change Science Teaching through Integration of Technology in Instruction and Research

NASA Astrophysics Data System (ADS)

Sriharan, S.; Ozbay, G.; Robinson, L.; Klimkowski, V.

2015-12-01

This presentation demonstrates the importance of collaborations between the institutions with common focus on offering the academic program on climate change science. Virginia State University (VSU) developed and established the course on climate change and adaptation, AGRI 350 for undergraduates, in cooperation with two HBCUs, Delaware State University (DSU) and Morgan State University (MSU). This program was developed to enhance the science curriculum with funding from the USDA NIFA. The hands-on research opportunities for students were supported by the NSF HBCU UP Supplement Grant at VSU. The technical guidance and lesson plans were available through the courtesy of the AMS and faculty/student team training at the NCAR. In the initial stages, the faculty members participated in faculty development workshops hosted by the AMS and NCAR. This contributed to trained faculty members developing the courses on Climate Change at VSU, DSU, and MSU. To create awareness of global climate change and exposure of students to international programs, seven students from VSU, MSU, and DSU participated in the Climate Change course (ENS 320) at the University of Sunshine Coast (USC), Australia. This international experience included faculty members in using SimCLIM for climate change data into decision-making with regard to potential changes to cropping systems and tree growth. The Climate Change program at VSU, DSU, and MSU is emerging into comprehensive academic program which includes use of case studies and exchange of students' reflections with their peers through discussion board and videoconferencing, hands-on research on water quality monitoring and mapping the study sites, and integration of geospatial technologies and i-Tree. In addition, the students' engagement in intensive research was conducted through hands-on experience with Scanning Electron Microscopy in the Marine Science Department, University of Hawaii at Hilo in summer 2015.

The potential role of salt abuse on the risk for kidney stone formation

NASA Technical Reports Server (NTRS)

Sakhaee, K.; Harvey, J. A.; Padalino, P. K.; Whitson, P.; Pak, C. Y.

1993-01-01

The kidney stone-forming risk of a high sodium diet was evaluated by assessing the effect of such a diet on the crystallization of stone-forming salts in urine. Fourteen normal subjects participated in 2 phases of study of 10 days duration each, comprising a low sodium phase (basal metabolic diet containing 50 mmol. sodium per day) and a high sodium phase (basal diet plus 250 mmol. sodium chloride per day). The high sodium intake significantly increased urinary sodium (34 +/- 12 to 267 +/- 56 mmol. per day), calcium (2.73 +/- 1.03 to 3.93 +/- 1.51 mmol. per day) and pH (5.79 +/- 0.44 to 6.15 +/- 0.25), and significantly decreased urinary citrate (3.14 +/- 1.19 to 2.52 +/- 0.83 mmol. per day). Arterialized venous blood bicarbonate and total serum carbon dioxide concentrations decreased significantly during the high sodium diet, whereas serum chloride concentration increased. However, no change in arterialized venous pH was detected. Thus, a high sodium intake not only increased calcium excretion, but also increased urinary pH and decreased citrate excretion. The latter effects are probably due to sodium-induced bicarbonaturia and a significant decrease in serum bicarbonate concentration, respectively. Commensurate with these changes, the urinary saturation of calcium phosphate (brushite) and monosodium urate increased, and the inhibitor activity against calcium oxalate crystallization (formation product) decreased. The net effect of a high sodium diet was an increased propensity for the crystallization of calcium salts in urine.

Full Monte-Carlo description of the Moscow State University Extensive Air Shower experiment

NASA Astrophysics Data System (ADS)

Fomin, Yu. A.; Kalmykov, N. N.; Karpikov, I. S.; Kulikov, G. V.; Kuznetsov, M. Yu.; Rubtsov, G. I.; Sulakov, V. P.; Troitsky, S. V.

2016-08-01

The Moscow State University Extensive Air Shower (EAS-MSU) array studied high-energy cosmic rays with primary energies ~ (1-500) PeV in the Northern hemisphere. The EAS-MSU data are being revisited following recently found indications to an excess of muonless showers, which may be interpreted as the first observation of cosmic gamma rays at ~ 100 PeV. In this paper, we present a complete Monte-Carlo model of the surface detector which results in a good agreement between data and simulations. The model allows us to study the performance of the detector and will be used to obtain physical results in further studies.

Determination of cloud fields from analysis of HIRS2/MSU sounding data. [20 channel infrared and 4 channel microwave atmospheric sounders

NASA Technical Reports Server (NTRS)

Susskind, J.; Reuter, D.

1986-01-01

IR and microwave remote sensing data collected with the HIRS2 and MSU sensors on the NOAA polar-orbiting satellites were evaluated for their effectiveness as bases for determining the cloud cover and cloud physical characteristics. Techniques employed to adjust for day-night alterations in the radiance fields are described, along with computational procedures applied to compare scene pixel values with reference values for clear skies. Sample results are provided for the mean cloud coverage detected over South America and Africa June 1979, with attention given to concurrent surface pressure and cloud top pressure values.

Current Concepts of Hyperuricemia and Gout

PubMed Central

Klinenberg, James R.

1969-01-01

Recent studies have confirmed that gout is an inborn error of metabolism. It has now become evident that the hyperuricemia associated with gout might occur either due to overproduction of uric acid, underexcretion of uric acid or a combination of these processes. Furthermore, patients with excessive purine synthesis may have a specific enzyme defect resulting in altered feedback inhibition of purine synthesis. A neurological disease manifest by mental retardation, choreo-athetosis, aggressive behavior, lip-biting and self-mutilation and associated with decidedly increased purine biosynthesis serves as a prototype of this kind of disorder. Other defects in regulation of purine biosynthesis have been postulated but their existence not yet confirmed. It has been demonstrated that urate crystals which are deposited from hyperuricemic body fluids set up an acute inflammatory reaction by means of a variety of chemical mediators. Thus, acute gouty arthritis is now recognized as an example of “crystal induced” synovitis. The treatment of gout consists of (1) the control of acute gouty attacks, and (2) the maintenance of normal serum uric acid concentrations. This latter may be achieved either with uricosuric drugs or with xanthine oxidase inhibition. With these principles in mind, it is now possible to avoid many of the severe crippling effects of gout and to restore the vast majority of gouty patients to useful and productive lives. PMID:5773483

[The clinical characteristics, diagnosis and treatment of patients with gout in China].

PubMed

Luo, H; Fang, W G; Zuo, X X; Wu, R; Li, X X; Chen, J W; Zhou, J G; Yang, J; Song, H; Duan, X J; Lin, X F; Zeng, X W; Zeng, H

2018-01-01

Objective: To investigate the demographic characteristics, clinical features, diagnosis and treatment of patients with gout in China. Methods: Clinical data of 6 814 patients with gout from 100 hospitals in 27 provinces, municipalities or autonomous regions in China were collected and analyzed. Results: (1) The ratio of male to female in patients with gout was 14.7∶1. The mean age of onset was (48.8±15.1) years old. Mean serum urate level was (526.7±132.3) μmol/L. Patients' education background was of U-shaped distribution; (2) Hypertension was the most common comorbidity [15.8%(1 079/6 814)], then overweight or obesity [51.9%(3 536/6 814)]; (3) Alcohol and high-purine food intake were dominant triggering factors in men. The diagnosis of gout was made after onset in majority of patients with cardinal symptom arthralgia. Most patients had the disease less than 5 years, and the longer the course, the more flares in the previous year of entry; (4) Febuxostat was the mostly used urate-lowering medication. 20.7%(1 412/6 814), 10.8%(739/6 814) and 3.9%(265/6 814) of patients were followed up in 4 weeks, 12 weeks and 24 weeks after registration, and 18.9%(267/1 412), 29.1%(215/739) and 38.1%(101/265) of them reached the control target of serum urate levels, respectively. After treatment, patients' liver function was not affected, but serum creatinine levels decreased significantly. Conclusions: The proportion of gout patients who reach target serum urate level is very low. Further steps including education and survey need to be carried on.

Prevalence of comorbidities and management of gout in a tropical city in Australia.

PubMed

Jeyaruban, Andrew; Soden, Muriel; Larkins, Sarah

2016-12-01

To examine the management of gout in general practice in Townsville, Australia, and to explore comorbid conditions in patients with gout. Study will also explore how closely guidelines are being followed in managing gout. Retrospective chart review was conducted from May to November 2014 in three general practices in Townsville. Registers for patients were established by searching "gout" and "gouty arthritis". Three hundred and twenty-one patients were included in the study after excluding inactive patients, patients below age of 18 and patients with cancer. Main outcome measures were prevalence of comorbidities in gout patients, gout medications and adequate serum urate control (≤0.36 mmol/l). Multivariate logistic regression was used to study the relationship between serum urate level, comorbid conditions and lifestyle factors. Hypertension was the most common comorbid condition with 60.8 % of patients followed by obesity and dyslipidaemia. In terms of medication, 46.7 % of patients were on allopurinol, 12.8 % on indomethacin and 13.4 % on diuretics. Eighty-six percentage of patients had serum urate level (sUA) recorded in the previous year. Of these, 32.2 % had a serum urate level below or equal to 0.36 mmol/l. Moreover, 17.4 % of patients had lifestyle advice documented in chart. Male gender was the most influential factor in having poor uric acid control (p < 0.01), followed by not being on allopurinol (p < 0.01) and patients older than 50 years (p = 0.02). Management of gout in this study sample was not entirely concordant with guidelines. The study also suggests a need for possible tighter monitoring and allopurinol dosing regime in older, male patients.

Patients with gout differ from healthy subjects in renal response to changes in serum uric acid.

PubMed

Liu, Sha; Perez-Ruiz, Fernando; Miner, Jeffrey N

2017-03-01

Our objectives were to determine whether a change in serum uric acid (sUA) resulted in a corresponding change in the fractional excretion of uric acid (FEUA) and whether the renal response was different in patients with gout versus healthy subjects. FEUA was calculated from previously published studies and four new phase I studies in healthy subjects and/or patients with gout before and after treatment to lower or raise sUA. Treatments included xanthine oxidase inhibitors to lower sUA as well as infusion of uric acid and provision of a high-purine diet to raise sUA. Plots were created of FEUA versus sUA before and after treatment. For the phase I studies, percent change in FEUA per mg/dL change in sUA was calculated separately for healthy subjects and patients with gout, and compared using Student's t test. Analysis of previously published data and the new phase I clinical data indicates that changing sUA by a non-renal mechanism leads to a change in FEUA. The magnitude of change is greater in subjects with higher baseline FEUA versus patients with gout. Healthy subjects excrete more urate than do patients with gout at physiological urate-filtered load; this difference disappears when the urate-filtered load is decreased to ∼5000mg/24hours. These observations are consistent with a less saturated urate reabsorption system in patients with gout versus healthy subjects, resulting in elevated retention of uric acid. Further investigation could lead to the discovery of mechanisms responsible for the etiology of hyperuricemia/gout. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

A urate gene-by-diuretic interaction and gout risk in participants with hypertension: results from the ARIC study.

PubMed

McAdams-DeMarco, Mara A; Maynard, Janet W; Baer, Alan N; Kao, Linda W; Kottgen, Anna; Coresh, Josef

2013-05-01

To test for a urate gene-by-diuretic interaction on incident gout. The Atherosclerosis Risk in Communities Study is a prospective population-based cohort of 15 792 participants recruited from four US communities (1987-1989). Participants with hypertension and available single nucleotide polymorphism (SNP) genotype data were included. A genetic urate score (GUS) was created from common urate-associated SNPs for eight genes. Gout incidence was self-reported. Using logistic regression, the authors estimated the adjusted OR of incident gout by diuretic use, stratified by GUS median. Of 3524 participants with hypertension, 33% used a diuretic and 3.1% developed gout. The highest 9-year cumulative incidence of gout was in those with GUS above the median and taking a thiazide or loop diuretic (6.3%). Compared with no thiazide or loop diuretic use, their use was associated with an OR of 0.40 (95% CI 0.14 to 1.15) among those with a GUS below the median and 2.13 (95% CI 1.23 to 3.67) for those with GUS above the median; interaction p=0.006. When investigating the genes separately, SLC22A11 and SLC2A9 showed a significant interaction, consistent with the former encoding an organic anion/dicarboxylate exchanger, which mediates diuretic transport in the kidney. Participants who were genetically predisposed to hyperuricaemia were susceptible to developing gout when taking thiazide or loop diuretics, an effect not evident among those without a genetic predisposition. These findings argue for a potential benefit of genotyping individuals with hypertension to assess gout risk, relative in part to diuretic use.

A urate gene-by-diuretic interaction and gout risk in participants with hypertension: results from the ARIC study

PubMed Central

McAdams-DeMarco, Mara A; Maynard, Janet W; Baer, Alan N; Kao, Linda W; Kottgen, Anna; Coresh, Josef

2015-01-01

Objective To test for a urate gene-by-diuretic interaction on incident gout. Methods The Atherosclerosis Risk in Communities Study is a prospective population-based cohort of 15 792 participants recruited from four US communities (1987–1989). Participants with hypertension and available single nucleotide polymorphism (SNP) genotype data were included. A genetic urate score (GUS) was created from common urate-associated SNPs for eight genes. Gout incidence was self-reported. Using logistic regression, the authors estimated the adjusted OR of incident gout by diuretic use, stratified by GUS median. Results Of 3524 participants with hypertension, 33% used a diuretic and 3.1% developed gout. The highest 9-year cumulative incidence of gout was in those with GUS above the median and taking a thiazide or loop diuretic (6.3%). Compared with no thiazide or loop diuretic use, their use was associated with an OR of 0.40 (95% CI 0.14 to 1.15) among those with a GUS below the median and 2.13 (95% CI 1.23 to 3.67) for those with GUS above the median; interaction p=0.006. When investigating the genes separately, SLC22A11 and SLC2A9 showed a significant interaction, consistent with the former encoding an organic anion/dicarboxylate exchanger, which mediates diuretic transport in the kidney. Conclusions Participants who were genetically predisposed to hyperuricaemia were susceptible to developing gout when taking thiazide or loop diuretics, an effect not evident among those without a genetic predisposition. These findings argue for a potential benefit of genotyping individuals with hypertension to assess gout risk, relative in part to diuretic use. PMID:22753387

Rationale and Design of the Randomized Evaluation of an Ambulatory Care Pharmacist-Led Intervention to Optimize Urate Lowering Pathways (RAmP-UP) Study

PubMed Central

Coburn, Brian W; Cheetham, T Craig; Rashid, Nazia; Chang, John M; Levy, Gerald D; Kerimian, Artak; Low, Kimberly J; Redden, David T; Bridges, S Louis; Saag, Kenneth G; Curtis, Jeffrey R; Mikuls, Ted R

2016-01-01

Background Despite the availability of effective therapies, most gout patients achieve suboptimal treatment outcomes. Current best practices suggest gradual dose-escalation of urate lowering therapy and serial serum urate (sUA) measurement to achieve sUA < 6.0 mg/dl. However, this strategy is not routinely used. Here we present the study design rationale and development for a pharmacist-led intervention to promote sUA goal attainment. Methods To overcome barriers in achieving optimal outcomes, we planned and implemented the Randomized Evaluation of an Ambulatory Care Pharmacist-Led Intervention to Optimize Urate Lowering Pathways (RAmP-UP) study. This is a large pragmatic cluster-randomized trial designed to assess a highly automated, pharmacist-led intervention to optimize allopurinol treatment in gout. Ambulatory clinics (n=101) from a large health system were randomized to deliver either the pharmacist-led intervention or usual care to gout patients over the age of 18 years newly initiating allopurinol. All participants received educational materials and could opt-out of the study. For intervention sites, pharmacists conducted outreach primarily via an automated telephone interactive voice recognition system. The outreach, guided by a gout care algorithm developed for this study, systematically promoted adherence assessment, facilitated sUA testing, provided education, and adjusted allopurinol dosing. The primary study outcomes are achievement of sUA < 6.0 mg/dl and treatment adherence determined after one year. With follow-up ongoing, study results will be reported subsequently. Conclusion Ambulatory care pharmacists and automated calling technology represent potentially important, underutilized resources for improving health outcomes for gout patients. PMID:27449546

Rationale and design of the randomized evaluation of an Ambulatory Care Pharmacist-Led Intervention to Optimize Urate Lowering Pathways (RAmP-UP) Study.

PubMed

Coburn, Brian W; Cheetham, T Craig; Rashid, Nazia; Chang, John M; Levy, Gerald D; Kerimian, Artak; Low, Kimberly J; Redden, David T; Bridges, S Louis; Saag, Kenneth G; Curtis, Jeffrey R; Mikuls, Ted R

2016-09-01

Despite the availability of effective therapies, most gout patients achieve suboptimal treatment outcomes. Current best practices suggest gradual dose-escalation of urate lowering therapy and serial serum urate (sUA) measurement to achieve sUA<6.0mg/dl. However, this strategy is not routinely used. Here we present the study design rationale and development for a pharmacist-led intervention to promote sUA goal attainment. To overcome barriers in achieving optimal outcomes, we planned and implemented the Randomized Evaluation of an Ambulatory Care Pharmacist-Led Intervention to Optimize Urate Lowering Pathways (RAmP-UP) study. This is a large pragmatic cluster-randomized trial designed to assess a highly automated, pharmacist-led intervention to optimize allopurinol treatment in gout. Ambulatory clinics (n=101) from a large health system were randomized to deliver either the pharmacist-led intervention or usual care to gout patients over the age of 18years newly initiating allopurinol. All participants received educational materials and could opt-out of the study. For intervention sites, pharmacists conducted outreach primarily via an automated telephone interactive voice recognition system. The outreach, guided by a gout care algorithm developed for this study, systematically promoted adherence assessment, facilitated sUA testing, provided education, and adjusted allopurinol dosing. The primary study outcomes are achievement of sUA<6.0mg/dl and treatment adherence determined after one year. With follow-up ongoing, study results will be reported subsequently. Ambulatory care pharmacists and automated calling technology represent potentially important, underutilized resources for improving health outcomes for gout patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Consumption of strawberries on a daily basis increases the non-urate 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging activity of fasting plasma in healthy subjects

PubMed Central

Prymont-Przyminska, Anna; Zwolinska, Anna; Sarniak, Agata; Wlodarczyk, Anna; Krol, Maciej; Nowak, Michal; de Graft-Johnson, Jeffrey; Padula, Gianluca; Bialasiewicz, Piotr; Markowski, Jaroslaw; Rutkowski, Krzysztof P.; Nowak, Dariusz

2014-01-01

Strawberries contain anthocyanins and ellagitanins which have antioxidant properties. We determined whether the consumption of strawberries increase the plasma antioxidant activity measured as the ability to decompose 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) in healthy subjects. The study involved 10 volunteers (age 41 ± 6 years, body weight 74.4 ± 12.7 kg) that consumed 500 g of strawberries daily for 9 days and 7 matched controls. Fasting plasma and spot morning urine samples were collected at baseline, during fruit consumption and after a 6 day wash-out period. DPPH decomposition was measured in both deproteinized native plasma specimens and pretreated with uricase (non-urate plasma). Twelve phenolics were determined with HPLC. Strawberries had no effect on the antioxidant activity of native plasma and circulating phenolics. Non-urate plasma DPPH decomposition increased from 5.7 ± 0.6% to 6.6 ± 0.6%, 6.5 ± 1.0% and 6.3 ± 1.4% after 3, 6 and 9 days of supplementation, respectively. The wash-out period reversed this activity back to 5.7 ± 0.8% (p<0.01). Control subjects did not reveal any changes of plasma antioxidant activity. Significant increase in urinary urolithin A and 4-hydroxyhippuric (by 8.7- and 5.9-times after 6 days of supplementation with fruits) was noted. Strawberry consumption can increase the non-urate plasma antioxidant activity which, in turn, may decrease the risk of systemic oxidants overactivity. PMID:25120279

Acupuncture for serum uric acid in patients with asymptomatic hyperuricemia: A randomized, double-blind, placebo-controlled trial.

PubMed

Huang, Yingjuan; Meng, Jun; Sun, Baoguo; Xiang, Ting; Zhou, Xin; Xu, Biyu; Wu, Yingzi; Chen, Zexiong; Zhang, Shijun

2017-04-01

Hyperuricemia (HUA) is the most common disease associated with cardiovascular disease, metabolic syndrome, hypertension, and kidney disease. The objective of the current study was to evaluate the preliminary efficacy, mechanism, and safety of acupuncture on serum uric acid in patients with asymptomatic HUA. A randomized, placebo-controlled trial among 123 patients with asymptomatic HUA was conducted. The acupoints used in the acupuncture group were bilateral Five Shu in Spleen Meridian. Each participant received the intervention once daily for 10 consecutive days. The sham group received the same treatment duration on the same acupoints by the Park Sham Device. All patients underwent measurements of serum or urine creatinine, uric acid, serum lipid profiles, fasting plasma glucose, HbA1c, xanthine oxidase (XOD) and urate-anion exchanger (URAT-1). At the end of the intervention, the individuals in the acupuncture group were found to have significantly less levels of serum uric acid than those in the sham group [(453±65 vs. 528±81) μmol/L, p<0.01]. Acupuncture was effective on increasing the urine uric acid level, urine pH value and 24-hour urine volume than the sham treatment (p<0.05 for all). Interestingly, acupuncture significantly decreased the level of URAT-1 (p<0.01) but not XOD than that of the sham intervention. The adverse events were that 3 patients experienced severe pain. Acupuncture on Five Shu in Spleen Meridian appeared to be safe and efficacious for decreasing serum uric acid in a Chinese HUA patient population. The mechanism might be associated with the decrease level of enzyme URAT-1. ChiCTR-TRC-13004122. Copyright © 2017 Elsevier B.V. All rights reserved.

Animal urine as painting materials in African rock art revealed by cluster ToF-SIMS mass spectrometry imaging.

PubMed

Mazel, Vincent; Richardin, Pascale; Touboul, David; Brunelle, Alain; Richard, Caroline; Laval, Eric; Walter, Philippe; Laprévote, Olivier

2010-08-01

The rock art site at the village of Songo in Mali is a very important Dogon ritual place where, since the end of the nineteenth century until today, takes place the ceremony of circumcision. During these ceremonies, paintings are performed on the walls of the shelter with mainly three colors: red, black and white. Ethnological literature mentions the use of animal urine of different species such as birds, lizards or snakes as a white pigment. Urine of these animals is mainly composed of uric acid or urate salts. In this article, time-of-flight secondary ion mass spectrometry (ToF-SIMS) is used to compare uric acid, snake urine and a sample of a white pigment of a Dogon painting coming from the rock art site of Songo. ToF-SIMS measurements in both positive and negative ion modes on reference compounds and snake urine proved useful for the study of uric acid and urate salts. This method enables to identify unambiguously these compounds owing to the detection in negative ion mode of the ion corresponding to the deprotonated molecule ([M-H](-) at m/z 167.01) and its fragment ions. Moreover, the mass spectra obtained in positive ion mode permit to differentiate uric acid and urate salts on the basis of specific ions. Applying this method to the Dogon white pigments sample, we show that the sample is entirely composed of uric acid. This proves for the first time, that animal urine was used as a pigment by the Dogon. The presence of uric acid instead of urate salts as normally expected in animal urine could be explained by the preparation of the pigment for its application on the stone. Copyright 2010 John Wiley & Sons, Ltd.

Genomic Influences on Hyperuricemia and Gout.

PubMed

Merriman, Tony

2017-08-01

Genome-wide association studies (GWAS) have identified nearly 30 loci associated with urate concentrations that also influence the subsequent risk of gout. The ABCG2 Q141 K variant is highly likely to be causal and results in internalization of ABCG2, which can be rescued by drugs. Three other GWAS loci contain uric acid transporter genes, which are also highly likely to be causal. However identification of causal genes at other urate loci is challenging. Finally, relatively little is known about the genetic control of progression from hyperuricemia to gout. Only 4 small GWAS have been published for gout. Copyright © 2017 Elsevier Inc. All rights reserved.

The safety of treatment options available for gout.

PubMed

Schlesinger, Naomi

2017-04-01

Gout is the most common inflammatory arthritis in humans. Gout treatment includes rapid initiation of anti-inflammatory medications for acute attacks and chronically treating with urate lowering drugs as well as chronic anti-inflammatory prophylaxis. Areas covered: This review aims to provide an overview and discussion of the safety concerns of current treatment options available for gout. Expert opinion: Gout is a curable disease with appropriate treatment. The advent of new therapies provides encouraging opportunities to improve gout management. However, clinicians should be aware of some of the safety concerns of medications used to treat acute and chronic gout. When prescribing medications for gout one has to be mindful of the presence of comorbidities commonly affecting gout patients that may affect drug safety and efficacy, especially in the elderly and in patients treated with multiple drugs. The benefits of gout drugs, usually, outweigh their safety concerns. Studies are needed in gout patients with chronic kidney disease and/or cardiovascular disease, so that escalation of dosing /combination of anti-inflammatory drugs needed to suppress gouty inflammation as well as escalation of dosing/combination of urate lowering drugs needed to achieve target serum urate level will lead to better understanding of gout treatment safety issues.

[Shmakovka narzan mineral water in the treatment of chronic pyelonephritis in children].

PubMed

Olofinskiĭ, L A; Alekseeva, I L

1990-01-01

The impact of "Pasechnyĭ" spa of the Shmakovka health resort on the circadian urinary output, renal excretion of magnesium, calcium, nonorganic phosphorus, oxalates, uric acid, phospholipids, acido- and ammoniogenases, daily fluctuations of urinary pH was studied for the first time in 65 children with chronic pyelonephritis. In the presence of spa treatment the authors revealed a 75-100 per cent increase in the circadian urinary output, urinary excretion of magnesium, uric acid, ammonia, titrated acids, a decrease in the levels of calcium, oxalates, nonorganic phosphorus and acidification of the urine at 9 o'clock in the morning mainly in children with primary pyelonephritis and at 9 and 6 o'clock in the morning in patients with concurrent uricosuria. Other parameters were not significantly different from those in the controls. Acidification of the urine in the presence of high uricosuria resulted in crystalluria of urates and oxalates in 26.31 per cent of patients with the concurrent urate diathesis. The water of Shmakovka mineral springs is recommended for patients with primary pyelonephritis, phosphaturia and calcium oxalate crystalluria with alkaline reaction of the urine and unjustified for those who suffered from urate diathesis.

Active Struts With Variable Spring Stiffness and Damping

NASA Technical Reports Server (NTRS)

Farley, Gary L.

2006-01-01

An ultrasonic rock-abrasion tool (URAT) was developed using the same principle of ultrasonic/sonic actuation as that of the tools described in two prior NASA Tech Briefs articles: Ultrasonic/ Sonic Drill/Corers With Integrated Sensors (NPO-20856), Vol. 25, No. 1 (January 2001), page 38 and Ultrasonic/ Sonic Mechanisms for Drilling and Coring (NPO-30291), Vol. 27, No. 9 (September 2003), page 65. Hence, like those tools, the URAT offers the same advantages of low power demand, mechanical simplicity, compactness, and ability to function with very small axial loading (very small contact force between tool and rock). Like a tool described in the second of the cited previous articles, a URAT includes (1) a drive mechanism that comprises a piezoelectric ultrasonic actuator, an amplification horn, and a mass that is free to move axially over a limited range and (2) an abrasion tool bit. A URAT tool bit is a disk that has been machined or otherwise formed to have a large number of teeth and an overall shape chosen to impart the desired shape (which could be flat or curved) to the rock surface to be abraded. In operation, the disk and thus the teeth are vibrated in contact with the rock surface. The concentrated stresses at the tips of the impinging teeth repeatedly induce microfractures and thereby abrade the rock. The motion of the tool induces an ultrasonic transport effect that displaces the cuttings from the abraded area. The figure shows a prototype URAT. A piezoelectric-stack/horn actuator is housed in a cylindrical container. The movement of the actuator and bit with respect to the housing is aided by use of mechanical sliders. A set of springs accommodates the motion of the actuator and bit into or out of the housing through an axial range between 5 and 7 mm. The springs impose an approximately constant force of contact between the tool bit and the rock to be abraded. A dust shield surrounds the bit, serving as a barrier to reduce the migration of rock debris to sensitive instrumentation or mechanisms in the vicinity. A bushing at the tool-bit end of the housing reduces the flow of dust into the actuator and retains the bit when no axial load is applied.

Ultrasonically Actuated Tools for Abrading Rock Surfaces

NASA Technical Reports Server (NTRS)

Dolgin, Benjamin; Sherrit, Stewart; Bar-Cohen, Yoseph; Rainen, Richard; Askin, Steve; Bickler, Donald; Lewis, Donald; Carson, John; Dawson, Stephen; Bao, Xiaoqi;

Urate oxidase for the prevention and treatment of tumour lysis syndrome in children with cancer.

PubMed

Cheuk, Daniel K L; Chiang, Alan K S; Chan, Godfrey C F; Ha, Shau Yin

2014-08-14

Tumour lysis syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Preliminary reports suggest that urate oxidase is effective in reducing serum uric acid, the build-up of which causes TLS. It is uncertain whether high-quality evidence exists to support its routine use in children with malignancies. To assess the effects and safety of urate oxidase for the prevention and treatment of TLS in children with malignancies. This is an update of the original review. We performed a comprehensive search of the Cochrane Central Register of Controlled Trials (CENTRAL) (in The Cochrane Library issue 1, 2013), MEDLINE (1966 to February 2013), Embase (1980 to February 2013), and CINAHL (1982 to February 2013). In addition, we searched the reference lists of all identified relevant papers. We also explored other internet sources (updated search on 26 February 2013): the NHS' National Research Register, the US National Institutes of Health Ongoing Trials Register, the metaRegister of Controlled Trials, and ProQuest Dissertations & Theses Database. We also screened conference proceedings of the American Society of Clinical Oncology, the European Society for Medical Oncology, and the International Society of Paediatric Oncology meetings from 1993 to 2012. Finally, we contacted experts in the field and the manufacturer of rasburicase, Sanofi-aventis. Randomised controlled trials (RCT) and controlled clinical trials (CCT) of urate oxidase for the prevention or treatment of TLS in children under 18 years with any malignancy. Two review authors independently extracted trial data and assessed individual trial quality. We used risk ratios (RR) for dichotomous data and mean difference (MD) for continuous data. We included seven trials, involving 471 participants in the treatment groups and 603 participants in the control groups. One RCT and five CCTs compared urate oxidase and allopurinol. Three trials tested Uricozyme, and three trials tested rasburicase for the prevention of TLS.The RCT showed no significant difference in mortality (both all-cause mortality and mortality due to TLS), renal failure, and adverse effects between the treatment and the control groups. The frequency of normalisation of uric acid at four hours (Fisher's exact test P < 0.001) and area under curve of uric acid at four days (MD -201.00 mg/dLhr, 95% confidence interval (CI) -258.05 mg/dLhr to -143.95 mg/dLhr; P < 0.00001) were significantly better in the treatment group. The trial did not evaluate the primary outcome (incidence of clinical TLS).Pooled results of three CCTs showed significantly lower mortality due to TLS in the treatment group (RR 0.05, 95% CI 0.00 to 0.89; P = 0.04); all-cause mortality was not significantly different between the groups. Pooled results from five CCTs showed significantly lower incidence of renal failure in the treatment group (RR 0.26, 95% CI 0.08 to 0.89; P = 0.03). Results of CCTs also showed significantly lower uric acid in the treatment group at two days (three CCTs), three days (two CCTs), four days (two CCTs), and seven days (one CCT) after therapy, but not one day (three CCTs), five days (one CCT), and 12 days (one CCT) after therapy. Pooled results from three CCTs showed higher frequency of adverse effects in participants who received urate oxidase (RR 9.10, 95% CI 1.29 to 64.00; P = 0.03). One CCT evaluated the primary outcome; no significant difference was identified.Another included RCT, with 30 participants, compared different doses of rasburicase (0.2 mg/kg versus 0.15 mg/kg), which demonstrated no significant difference in uric acid normalisation and uric acid level at four hours). Common adverse events of urate oxidase included hypersensitivity, haemolysis, and anaemia, but no significant difference between treatment groups was identified. No significant difference in mortality (all-cause mortality and mortality due to TLS) and renal failure was identified. The primary outcome was not evaluated.All included trials were highly susceptible to biases. Although urate oxidase might be effective in reducing serum uric acid, it is unclear whether it reduces clinical tumour lysis syndrome, renal failure, or mortality. Adverse effects might be more common for urate oxidase compared with allopurinol. Clinicians should weigh the potential benefits of reducing uric acid and uncertain benefits of preventing mortality or renal failure from TLS against the potential risk of adverse effects.

One library's experience with review and selection of chat software for reference.

PubMed

Behm, Leslie M

2003-01-01

When Michigan State University (MSU) Libraries decided to make the foray into virtual reference, the first thing that needed to be done was to decide on the software to use. This article discusses the process used including the items considered essential (deal-breakers) for software to make the first cut, what other features needed to be included, and what features would be useful but were not critical. A literature review of some useful current articles on virtual reference is included. The vendor and software ultimately selected was not one of the original vendors; how MSU Libraries was able to evaluate and select Docutek is presented. A matrix for software comparison is included in the appendix.

Draft genome sequence of Xylaria sp., the causal agent of taproot decline of soybean in the southern United States.

PubMed

Sharma, Sandeep; Zaccaron, Alex Z; Ridenour, John B; Allen, Tom W; Conner, Kassie; Doyle, Vinson P; Price, Trey; Sikora, Edward; Singh, Raghuwinder; Spurlock, Terry; Tomaso-Peterson, Maria; Wilkerson, Tessie; Bluhm, Burton H

2018-04-01

The draft genome of Xylaria sp. isolate MSU_SB201401, causal agent of taproot decline of soybean in the southern U.S., is presented here. The genome assembly was 56.7 Mb in size with an L50 of 246. A total of 10,880 putative protein-encoding genes were predicted, including 647 genes encoding carbohydrate-active enzymes and 1053 genes encoding secreted proteins. This is the first draft genome of a plant-pathogenic Xylaria sp. associated with soybean. The draft genome of Xylaria sp. isolate MSU_SB201401 will provide an important resource for future experiments to determine the molecular basis of pathogenesis.

Superconducting Resonators Development for the FRIB and ReA Linacs at MSU: Recent Achievements and Future Goals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Facco, A; Binkowski, J; Compton, C

2012-07-01

The superconducting driver and post-accelerator linacs of the FRIB project, the large scale radioactive beam facility under construction at MSU, require the construction of about 400 low-{beta} Quarter-wave (QWR) and Half-wave resonators (HWR) with four different optimum velocities. 1st and 2nd generation prototypes of {beta}{sub 0} = 0.041 and 0.085 QWRs and {beta}{sub 0} = 0.53 HWRs have been built and tested, and have more than fulfilled the FRIB and ReA design goals. The present cavity surface preparation at MSU allowed production of low-{beta} cavities nearly free from field emission. The first two cryostats of {beta}{sub 0} = 0.041 QWRsmore » are now in operation in the ReA3 linac. A 3rd generation design of the FRIB resonators allowed to further improve the cavity parameters, reducing the peak magnetic field in operation and increasing the possible operation gradient, with consequent reduction of the number of required resonators. The construction of the cavities for FRIB, which includes three phases for each cavity type (development, pre-production and production runs) has started. Cavity design, construction, treatment and performance will be described and discussed.« less

Hyaline cartilage involvement in patients with gout and calcium pyrophosphate deposition disease. An ultrasound study.

PubMed

Filippucci, E; Riveros, M Gutierrez; Georgescu, D; Salaffi, F; Grassi, W

2009-02-01

The main aim of the present study was to determine the sensitivity, specificity and accuracy of ultrasonography (US) in detecting monosodium urate and calcium pyrophosphate dihydrate crystals deposits at knee cartilage level using clinical definite diagnosis as standard reference. A total of 32 patients with a diagnosis of gout and 48 patients with pyrophosphate arthropathy were included in the study. Fifty-two patients with rheumatoid arthritis (RA), psoriatic arthritis or osteoarthritis (OA) were recruited as disease controls. All diagnoses were made using an international clinical criterion. US examinations were performed by an experienced sonographer, blind to clinical and laboratory data. Hyaline cartilage was assessed to detect two US findings recently indicated as indicative of crystal deposits: hyperechoic enhancement of the superficial margin of the hyaline cartilage and hyperechoic spots within the cartilage layer not generating a posterior acoustic shadow. Hyperechoic enhancement of the chondrosynovial margin was found in at least one knee of 14 out of 32 (43.7%) patients with gout and in a single knee of only one patient affected by pyrophosphate arthropathy (specificity=99%). Intra-cartilaginous hyperechoic spots were detected in at least one knee of 33 out of 48 (68.7%) patients with pyrophosphate arthropathy and in two disease controls one with OA and the second with RA (specificity=97.6%). The results of the present study indicate that US may play a relevant role in distinguishing cartilage involvement in patients with crystal-related arthropathy. The selected US findings were found to be highly specific.

Current and future therapies for gout.

PubMed

Pascart, Tristan; Richette, Pascal

2017-08-01

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. Expert opinion: Recent data provide a good grasp of the optimal use of colchicine, corticosteroids and NSAIDs for the treatment of flares. Interleukin-1 blocking therapies have an increasing role in the management of difficult-to-treat gout. Sub-optimal use of allopurinol is common and its potency to reduce serum uric acid (SUA) levels is underestimated. Febuxostat effectively reduces SUA levels. New uricosurics, notably lesinurad and arhalofenate, in combination with xanthine oxidase inhibitors, offer promising perspectives to help a greater number of patients achieve sufficient SUA reduction.

Comparison of the effects of firocoxib, carprofen and vedaprofen in a sodium urate crystal induced synovitis model of arthritis in dogs.

PubMed

Hazewinkel, Herman A W; van den Brom, Walter E; Theyse, Lars F H; Pollmeier, Matthias; Hanson, Peter D

2008-02-01

A randomized, placebo-controlled, four-period cross-over laboratory study involving eight dogs was conducted to confirm the effective analgesic dose of firocoxib, a selective COX-2 inhibitor, in a synovitis model of arthritis. Firocoxib was compared to vedaprofen and carprofen, and the effect, defined as a change in weight bearing measured via peak ground reaction, was evaluated at treatment dose levels. A lameness score on a five point scale was also assigned to the affected limb. Peak vertical ground reaction force was considered to be the most relevant measurement in this study. The firocoxib treatment group performed significantly better than placebo at the 3 h post-treatment time point and significantly better than placebo and carprofen at the 7 h post-treatment time point. Improvement in lameness score was also significantly better in the dogs treated with firocoxib than placebo and carprofen at both the 3 and 7 h post-treatment time points.

Catching the PEG-induced attractive interaction between proteins.

PubMed

Vivarès, D; Belloni, L; Tardieu, A; Bonneté, F

2002-09-01

We present the experimental and theoretical background of a method to characterize the protein-protein attractive potential induced by one of the mostly used crystallizing agents in the protein-field, the poly(ethylene glycol) (PEG). This attractive interaction is commonly called, in colloid physics, the depletion interaction. Small-Angle X-ray Scattering experiments and numerical treatments based on liquid-state theories were performed on urate oxidase-PEG mixtures with two different PEGs (3350 Da and 8000 Da). A "two-component" approach was used in which the polymer-polymer, the protein-polymer and the protein-protein pair potentials were determined. The resulting effective protein-protein potential was characterized. This potential is the sum of the free-polymer protein-protein potential and of the PEG-induced depletion potential. The depletion potential was found to be hardly dependent upon the protein concentration but strongly function of the polymer size and concentration. Our results were also compared with two models, which give an analytic expression for the depletion potential.

Global Warming Estimation from MSU: Correction for Drift and Calibration Errors

NASA Technical Reports Server (NTRS)

Prabhakara, C.; Iacovazzi, R., Jr.; Yoo, J.-M.; Einaudi, Franco (Technical Monitor)

2000-01-01

Microwave Sounding Unit (MSU) radiometer observations in Ch 2 (53.74 GHz), made in the nadir direction from sequential, sun-synchronous, polar-orbiting NOAA morning satellites (NOAA 6, 10 and 12 that have about 7am/7pm orbital geometry) and afternoon satellites (NOAA 7, 9, 11 and 14 that have about 2am/2pm orbital geometry) are analyzed in this study to derive global temperature trend from 1980 to 1998. In order to remove the discontinuities between the data of the successive satellites and to get a continuous time series, first we have used shortest possible time record of each satellite. In this way we get a preliminary estimate of the global temperature trend of 0.21 K/decade. However, this estimate is affected by systematic time-dependent errors. One such error is the instrument calibration error. This error can be inferred whenever there are overlapping measurements made by two satellites over an extended period of time. From the available successive satellite data we have taken the longest possible time record of each satellite to form the time series during the period 1980 to 1998 to this error. We find we can decrease the global temperature trend by about 0.07 K/decade. In addition there are systematic time dependent errors present in the data that are introduced by the drift in the satellite orbital geometry arises from the diurnal cycle in temperature which is the drift related change in the calibration of the MSU. In order to analyze the nature of these drift related errors the multi-satellite Ch 2 data set is partitioned into am and pm subsets to create two independent time series. The error can be assessed in the am and pm data of Ch 2 on land and can be eliminated. Observations made in the MSU Ch 1 (50.3 GHz) support this approach. The error is obvious only in the difference between the pm and am observations of Ch 2 over the ocean. We have followed two different paths to assess the impact of the errors on the global temperature trend. In one path the entire error is placed in the am data while in the other it is placed in the pm data. Global temperature trend is increased or decreased by about 0.03 K/decade depending upon this placement. Taking into account all random errors and systematic errors our analysis of MSU observations leads us to conclude that a conservative estimate of the global warming is 0. 11 (+-) 0.04 K/decade during 1980 to 1998.

Are ultrasound features at the first metatarsophalangeal joint associated with clinically-assessed pain and function? A study of people with gout, asymptomatic hyperuricaemia and normouricaemia.

PubMed

Stewart, Sarah; Dalbeth, Nicola; Vandal, Alain C; Allen, Bruce; Miranda, Rhian; Rome, Keith

2017-01-01

The first metatatarsophalangeal joint (1st MTP joint) is a common location for sonographic evidence of urate deposition in people with gout and asymptomatic hyperuricaemia. However, it is unclear whether these are related to clinically-assessed pain and function. This study aimed to determine the association between ultrasound features and clinical characteristics of the 1st MTP joint in people with gout, asymptomatic hyperuricaemia and age- and sex-matched normouricaemic individuals. Twenty-three people with gout, 29 with asymptomatic hyperuricaemia and 34 with normouricaemia participated in a cross-sectional study. No participant had clinical evidence of acute inflammatory arthritis at the time of assessment. Four sonographic features at the 1st MTP joint were analysed: double contour sign, tophus, bone erosion and synovitis. Clinical characteristics included in the analysis were 1st MTP joint pain, overall foot pain and disability, 1st MTP joint temperature, 1st MTP joint range of motion and gait velocity. Statistical analyses adjusted for the diagnostic group of the participant. After accounting for the diagnostic group, double contour sign was associated with higher foot pain and disability scores ( P  < 0.001). Ultrasound tophus was associated with higher foot pain and disability scores ( P  < 0.001), increased temperature ( P  = 0.005), and reduced walking velocity ( P  = 0.001). No associations were observed between ultrasound synovitis or erosion and the clinical characteristics. Ultrasound features of urate crystal deposition, rather than soft tissue inflammation or bone erosion, are associated with clinical measures of foot-related functional impairment and disability even in the absence of clinical evidence of current acute inflammatory arthritis. This association persisted regardless of the diagnosis of the participant as having gout or asymptomatic hyperuricaemia.

Hydrodeoxygenation of Pyrolysis Bio-Oil Over Ni Impregnated Mesoporous Materials.

PubMed

Lee, In-Gu; Lee, Heejin; Kang, Bo Sung; Kim, Young-Min; Kim, Sang Chai; Jung, Sang-Chul; Ko, Chang Hyun; Park, Young-Kwon

2018-02-01

The catalytic hydrodeoxygenation (HDO) of bio-oil over Ni-supported mesoporous materials was performed using a high pressure autoclave reactor. The actual pyrolysis oil of cork oak wood was used as a sample, and Ni/Al-SBA-15 and Ni/Al-MSU-F were used as catalysts. In addition, supercritical ethanol was added as solvent. Both Ni-supported mesoporous catalysts showed efficient HDO reaction ability. A higher heating value and pH of bio-oil were achieved by the HDO reaction over both catalysts and upgraded bio-oil had a lower viscosity. Compared to Ni/Al-MSU-F, Ni/Al- SBA-15 produced more upgraded bio-oil with a lower oxygen content and higher heating value via a catalytic HDO process.

The Montana ALE (Autonomous Lunar Excavator) Systems Engineering Report

NASA Technical Reports Server (NTRS)

Hull, Bethanne J.

2012-01-01

On May 2 1-26, 20 12, the third annual NASA Lunabotics Mining Competition will be held at the Kennedy Space Center in Florida. This event brings together student teams from universities around the world to compete in an engineering challenge. Each team must design, build and operate a robotic excavator that can collect artificial lunar soil and deposit it at a target location. Montana State University, Bozeman, is one of the institutions selected to field a team this year. This paper will summarize the goals of MSU's lunar excavator project, known as the Autonomous Lunar Explorer (ALE), along with the engineering process that the MSU team is using to fulfill these goals, according to NASA's systems engineering guidelines.

The renal urate transporter SLC17A1 locus: confirmation of association with gout.

PubMed

Hollis-Moffatt, Jade E; Phipps-Green, Amanda J; Chapman, Brett; Jones, Gregory T; van Rij, Andre; Gow, Peter J; Harrison, Andrew A; Highton, John; Jones, Peter B; Montgomery, Grant W; Stamp, Lisa K; Dalbeth, Nicola; Merriman, Tony R

2012-04-27

Two major gout-causing genes have been identified, the urate transport genes SLC2A9 and ABCG2. Variation within the SLC17A1 locus, which encodes sodium-dependent phosphate transporter 1, a renal transporter of uric acid, has also been associated with serum urate concentration. However, evidence for association with gout is equivocal. We investigated the association of the SLC17A1 locus with gout in New Zealand sample sets. Five variants (rs1165196, rs1183201, rs9358890, rs3799344, rs12664474) were genotyped across a New Zealand sample set totaling 971 cases and 1,742 controls. Cases were ascertained according to American Rheumatism Association criteria. Two population groups were studied: Caucasian and Polynesian. At rs1183201 (SLC17A1), evidence for association with gout was observed in both the Caucasian (odds ratio (OR) = 0.67, P = 3.0 × 10-6) and Polynesian (OR = 0.74, P = 3.0 × 10-3) groups. Meta-analysis confirmed association of rs1183201 with gout at a genome-wide level of significance (OR = 0.70, P = 3.0 × 10-8). Haplotype analysis suggested the presence of a common protective haplotype. We confirm the SLC17A1 locus as the third associated with gout at a genome-wide level of significance.

Salivary uric acid as a noninvasive biomarker for monitoring the efficacy of urate-lowering therapy in a patient with chronic gouty arthropathy.

PubMed

Zhao, Jianxing; Huang, Ying

2015-10-23

Monitoring blood uric acid (UA) is important in all patients on urate-lowering therapy so that the selection of the effective drugs and dosage adjustments could be made until the target level is reached. The issue is that frequent needle jabs are unacceptable. Reported mean levels of salivary UA were 185-240 μmol/l in healthy adults. A linear correlation was demonstrated between UA concentrations in saliva and plasma. We monitored salivary UA instead of plasmatic UA in a patient with gout. Allopurinol and benzbromarone were used as the therapeutic drugs. Salivary UA; urinary UA and creatinine; and plasmatic UA, creatinine, kynurenine and tryptophan were measured by HPLC. Salivary UA indicated the efficacy of therapy accurately and conveniently. After eight weeks therapy, the weekly mean levels of salivary UA were reduced and maintained to <300 μmol/l, which was equivalent to <360 μmol/l of plasmatic UA according to the salivary UA/plasmatic UA ratio of this patient. Measurement of salivary UA is a noninvasive and useful way for monitoring the status of hyperuricemia and the therapeutic efficacy of urate-lowering therapy. It has value for the management of hyperuricemia and gout. Copyright © 2015 Elsevier B.V. All rights reserved.

Management of Acute and Recurrent Gout: A Clinical Practice Guideline From the American College of Physicians.

PubMed

Qaseem, Amir; Harris, Russell P; Forciea, Mary Ann

2017-01-03

The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the management of gout. Using the ACP grading system, the committee based these recommendations on a systematic review of randomized, controlled trials; systematic reviews; and large observational studies published between January 2010 and March 2016. Clinical outcomes evaluated included pain, joint swelling and tenderness, activities of daily living, patient global assessment, recurrence, intermediate outcomes of serum urate levels, and harms. The target audience for this guideline includes all clinicians, and the target patient population includes adults with acute or recurrent gout. ACP recommends that clinicians choose corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or colchicine to treat patients with acute gout. (Grade: strong recommendation, high-quality evidence). ACP recommends that clinicians use low-dose colchicine when using colchicine to treat acute gout. (Grade: strong recommendation, moderate-quality evidence). ACP recommends against initiating long-term urate-lowering therapy in most patients after a first gout attack or in patients with infrequent attacks. (Grade: strong recommendation, moderate-quality evidence). ACP recommends that clinicians discuss benefits, harms, costs, and individual preferences with patients before initiating urate-lowering therapy, including concomitant prophylaxis, in patients with recurrent gout attacks. (Grade: strong recommendation, moderate-quality evidence).

Management of hyperuricemia in gout: focus on febuxostat

PubMed Central

Reinders, Mattheus K; Jansen, Tim L Th A

2010-01-01

Gout is the most common inflammatory arthritis in an elderly population, and can be diagnosed with absolute certainty by polarization microscopy. However, diagnosis may be challenging because atypical presentations are more common in the elderly. Management of hyperuricemia in the elderly with gout requires special consideration because of co-medication, contra-indications, and risk of adverse reactions. Urate-lowering agents include allopurinol and uricosuric agents. These also must be used sensibly in the elderly, especially when renal function impairment is present. However, if used at the lowest dose that maintains the serum urate level below 5.0 to 6.0 mg/dL (0.30 to 0.36 mmol/L), the excess urate in the body will eventually be eliminated, acute flares will no longer occur, and tophi will resolve. Febuxostat, a new xanthine oxidase inhibitor, is welcomed, as few alternatives for allopurinol are available. Its pharmacokinetics and pharmacodynamics are not significantly altered in patients with moderate renal function or hepatic impairment. Its antihyperuricemic efficacy at 80 to 120 mg/day is better than “standard dosage” allopurinol (300 mg/day). Long-term safety data and efficacy data on tophus diminishment and reduction of gout flares have recently become available. Febuxostat may provide an important option in patients unable to use allopurinol, or refractory to allopurinol. PMID:20169038

Taurine decreased uric acid levels in hyperuricemic rats and alleviated kidney injury.

PubMed

Feng, Ying; Sun, Fang; Gao, Yongchao; Yang, Jiancheng; Wu, Gaofeng; Lin, Shumei; Hu, Jianmin

2017-07-29

Hyperuricemia can lead to direct kidney damage. Taurine participates in several renal physiological processes and has been shown as a renoprotective agent. It has been reported that taurine could reduce uric acid levels in diabetic rats, but to date there was no research on the effects of taurine on hyperuricemic rats with kidney injury. In present study, hyperuricemic rat models were induced by intragastric administration of adenine and ethambutol hydrochloride for 10 days, and taurine (1% or 2%) were added in the drinking water 7 days in advance for consecutively 17 days. The results showed that taurine alleviated renal morphological and pathological changes as well as kidney dysfunction in hyperuricemic rats. Taurine could efficiently decrease the elevated xanthine oxidase activities in hyperuricemic rats, indicating its effect on the regulation of uric acid formation. The reabsorption and secretion of uric acid are dependent on a number of urate transporters. Expressions of three urate transporters were significantly down-regulated in hyperuricemic rats, while taurine prevented the decrease of mRNA and protein expression levels of these urate transporters. The results indicate that taurine might play a role in the regulation of renal uric acid excretion. Therefore, taurine could be a promising agent for the treatment of hyperuricemia. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanism of ascorbic acid interference in biochemical tests that use peroxide and peroxidase to generate chromophore.

PubMed

Martinello, Flávia; Luiz da Silva, Edson

2006-11-01

Ascorbic acid interferes negatively in peroxidase-based tests (Trinder method). However, the precise mechanism remains unclear for tests that use peroxide, a phenolic compound and 4-aminophenazone (4-AP). We determined the chemical mechanism of this interference, by examining the effects of ascorbic acid in the reaction kinetics of the production and reduction of the oxidized chromophore in urate, cholesterol, triglyceride and glucose tests. Reaction of ascorbic acid with the Trinder method constituents was also verified. Ascorbic acid interfered stoichiometrically with all tests studied. However, it had two distinct effects on the reaction rate. In the urate test, ascorbic acid decreased the chromophore formation with no change in its production kinetics. In contrast, in cholesterol, triglyceride and glucose tests, an increase in the lag phase of color development occurred. Of all the Trinder constituents, only peroxide reverted the interference. In addition, ascorbic acid did not interfere with oxidase activity nor reduce significantly the chromophore formed. Peroxide depletion was the predominant chemical mechanism of ascorbic acid interference in the Trinder method with phenolics and 4-AP. Distinctive effects of ascorbic acid on the reaction kinetics of urate, cholesterol, glucose and triglyceride might be due to the rate of peroxide production by oxidases.

Evaluating the urate-lowering effects of different microbial fermented extracts in hyperuricemic models accompanied with a safety study.

PubMed

Chen, Rong-Jane; Chen, Mei-Huei; Chen, Yen-Lin; Hsiao, Ching-Mao; Chen, Hsiu-Min; Chen, Siao-Jhen; Wu, Ming-Der; Yech, Yi-Jen; Yuan, Gwo-Fang; Wang, Ying-Jan

2017-07-01

Uric acid (UA) is an end product of purine metabolism by the enzyme xanthine oxidase (XOD). Hyperuricemia is characterized by the accumulation of serum UA and is an important risk factor for gout and many chronic disorders. XOD inhibitors or uricase (catalyzes UA to the more soluble end product) can prevent these chronic diseases. However, currently available hypouricemic agents induce severe side effects. Therefore, we developed new microbial fermented extracts (MFEs) with substantial XOD inhibition activity from Lactobacillus (MFE-21) and Acetobacter (MFE-25), and MFE-120 with high uricase activity from Aspergillus. The urate-lowering effects and safety of these MFEs were evaluated. Our results showed that MFE-25 exerts superior urate-lowering effects in the therapeutic model. In the preventive model, both MFE-120 and MFE-25 significantly reduced UA. The results of the safety study showed that no organ toxicity and no treatment-related adverse effects were observed in mice treated with high doses of MFEs. Taken together, the results showed the effectiveness of MFEs in reducing hyperuricemia without systemic toxicity in mice at high doses, suggesting that they are safe for use in the treatment and prevention of hyperuricemia. Copyright © 2016. Published by Elsevier B.V.

Dual-energy computed tomography as a diagnostic tool for gout during intercritical periods.

PubMed

Breuer, Gabriel S; Bogot, Naama; Nesher, Gideon

2016-12-01

The aim of this study is to evaluate the diagnostic yield of dual-energy computed tomography (DECT) in detection of uric acid accumulation in joints or periarticular structures in patients suspected of having gout, in their intercritical period. Patients with a history of recurrent, short-lived mono- or oligo-arthralgia or arthritis, referred to the rheumatology clinic for diagnosis of their condition, were included in this retrospective evaluation. DECT confirmed the diagnosis of gout in 30 of 50 patients (60%). A positive DECT was present in 12 of 16 cases (75%) with serum uric acid > 8.5 mg/dL, compared to seven of 13 cases (54%) and two of five cases (40%) with levels of 6.1-8.5 mg/dL and ≤ 6 mg/dL, respectively. The diagnostic impact of screening hands and feet were highest (78% and 56%, respectively). Follow-up data were available for 24 of the 30 patients with urate deposits identified by DECT. Twenty-one were treated with urate-lowering agents, all responded with lowering of serum uric acid and cessation of flares. Follow-up data were available for 16 of the 20 patients with no urate deposits identified by DECT. Gout was diagnosed in two of them by synovial fluid examination during subsequent flares. Both positive and negative predictive values of DECT for diagnosing gout in this patient population were 87%. Following DECT, treatment regimen was modified to gout-specific therapy in 52% of the patients. The ability to make a definite diagnosis of gout by DECT imaging in a substantial number of asymptomatic patients in the intercritical period should help in treatment decision-making and improve patient adherence to long-term urate-lowering therapy. © 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Complex analysis of urate transporters SLC2A9, SLC22A12 and functional characterization of non-synonymous allelic variants of GLUT9 in the Czech population: no evidence of effect on hyperuricemia and gout.

PubMed

Hurba, Olha; Mancikova, Andrea; Krylov, Vladimir; Pavlikova, Marketa; Pavelka, Karel; Stibůrková, Blanka

2014-01-01

Using European descent Czech populations, we performed a study of SLC2A9 and SLC22A12 genes previously identified as being associated with serum uric acid concentrations and gout. This is the first study of the impact of non-synonymous allelic variants on the function of GLUT9 except for patients suffering from renal hypouricemia type 2. The cohort consisted of 250 individuals (150 controls, 54 nonspecific hyperuricemics and 46 primary gout and/or hyperuricemia subjects). We analyzed 13 exons of SLC2A9 (GLUT9 variant 1 and GLUT9 variant 2) and 10 exons of SLC22A12 by PCR amplification and sequenced directly. Allelic variants were prepared and their urate uptake and subcellular localization were studied by Xenopus oocytes expression system. The functional studies were analyzed using the non-parametric Wilcoxon and Kruskall-Wallis tests; the association study used the Fisher exact test and linear regression approach. We identified a total of 52 sequence variants (12 unpublished). Eight non-synonymous allelic variants were found only in SLC2A9: rs6820230, rs2276961, rs144196049, rs112404957, rs73225891, rs16890979, rs3733591 and rs2280205. None of these variants showed any significant difference in the expression of GLUT9 and in urate transport. In the association study, eight variants showed a possible association with hyperuricemia. However, seven of these were in introns and the one exon located variant, rs7932775, did not show a statistically significant association with serum uric acid concentration. Our results did not confirm any effect of SLC22A12 and SLC2A9 variants on serum uric acid concentration. Our complex approach using association analysis together with functional and immunohistochemical characterization of non-synonymous allelic variants did not show any influence on expression, subcellular localization and urate uptake of GLUT9.

Final Project Report for Award ER65581

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stoy, Paul C.

2017-07-13

The attached final project report describes contributions of Montana State University (MSU) to the project "Bridging land-surface fluxes and aerosol concentrations to triggering convective rainfall" (PI: Fuentes).

ABCG2 variant has opposing effects on onset ages of Parkinson's disease and gout

PubMed Central

Matsuo, Hirotaka; Tomiyama, Hiroyuki; Satake, Wataru; Chiba, Toshinori; Onoue, Hiroyuki; Kawamura, Yusuke; Nakayama, Akiyoshi; Shimizu, Seiko; Sakiyama, Masayuki; Funayama, Manabu; Nishioka, Kenya; Shimizu, Toru; Kaida, Kenichi; Kamakura, Keiko; Toda, Tatsushi; Hattori, Nobutaka; Shinomiya, Nariyoshi

2015-01-01

Uric acid (urate) has been suggested to play a protective role in Parkinson's disease onset through its antioxidant activity. Dysfunction of ABCG2, a high-capacity urate exporter, is a major cause for early-onset gout based on hyperuricemia. In this study, the effects of a dysfunctional ABCG2 variant (Q141K, rs2231142) were analyzed on the ages at onset of gout patients (N = 507) and Parkinson's disease patients (N = 1015). The Q141K variant hastened the gout onset (P = 0.0027), but significantly associated with later Parkinson's disease onset (P = 0.025). Our findings will be helpful for development of more effective prevention of Parkinson's disease. PMID:25815357

ABCG2 variant has opposing effects on onset ages of Parkinson's disease and gout.

PubMed

Matsuo, Hirotaka; Tomiyama, Hiroyuki; Satake, Wataru; Chiba, Toshinori; Onoue, Hiroyuki; Kawamura, Yusuke; Nakayama, Akiyoshi; Shimizu, Seiko; Sakiyama, Masayuki; Funayama, Manabu; Nishioka, Kenya; Shimizu, Toru; Kaida, Kenichi; Kamakura, Keiko; Toda, Tatsushi; Hattori, Nobutaka; Shinomiya, Nariyoshi

2015-03-01

Uric acid (urate) has been suggested to play a protective role in Parkinson's disease onset through its antioxidant activity. Dysfunction of ABCG2, a high-capacity urate exporter, is a major cause for early-onset gout based on hyperuricemia. In this study, the effects of a dysfunctional ABCG2 variant (Q141K, rs2231142) were analyzed on the ages at onset of gout patients (N = 507) and Parkinson's disease patients (N = 1015). The Q141K variant hastened the gout onset (P = 0.0027), but significantly associated with later Parkinson's disease onset (P = 0.025). Our findings will be helpful for development of more effective prevention of Parkinson's disease.

Experience of the JPL Exploratory Data Analysis Team at validating HIRS2/MSU cloud parameters

NASA Technical Reports Server (NTRS)

Kahn, Ralph; Haskins, Robert D.; Granger-Gallegos, Stephanie; Pursch, Andrew; Delgenio, Anthony

1992-01-01

Validation of the HIRS2/MSU cloud parameters began with the cloud/climate feedback problem. The derived effective cloud amount is less sensitive to surface temperature for higher clouds. This occurs because as the cloud elevation increases, the difference between surface temperature and cloud temperature increases, so only a small change in cloud amount is needed to effect a large change in radiance at the detector. By validating the cloud parameters it is meant 'developing a quantitative sense for the physical meaning of the measured parameters', by: (1) identifying the assumptions involved in deriving parameters from the measured radiances, (2) testing the input data and derived parameters for statistical error, sensitivity, and internal consistency, and (3) comparing with similar parameters obtained from other sources using other techniques.

Identification of patients with gout: elaboration of a questionnaire for epidemiological studies.

PubMed

Richette, P; Clerson, P; Bouée, S; Chalès, G; Doherty, M; Flipo, R M; Lambert, C; Lioté, F; Poiraud, T; Schaeverbeke, T; Bardin, T

2015-09-01

In France, the prevalence of gout is currently unknown. We aimed to design a questionnaire to detect gout that would be suitable for use in a telephone survey by non-physicians and assessed its performance. We designed a 62-item questionnaire covering comorbidities, clinical features and treatment of gout. In a case-control study, we enrolled patients with a history of arthritis who had undergone arthrocentesis for synovial fluid analysis and crystal detection. Cases were patients with crystal-proven gout and controls were patients who had arthritis and effusion with no monosodium urate crystals in synovial fluid. The questionnaire was administered by phone to cases and controls by non-physicians who were unaware of the patient diagnosis. Logistic regression analysis and classification and regression trees were used to select items discriminating cases and controls. We interviewed 246 patients (102 cases and 142 controls). Two logistic regression models (sensitivity 88.0% and 87.5%; specificity 93.0% and 89.8%, respectively) and one classification and regression tree model (sensitivity 81.4%, specificity 93.7%) revealed 11 informative items that allowed for classifying 90.0%, 88.8% and 88.5% of patients, respectively. We developed a questionnaire to detect gout containing 11 items that is fast and suitable for use in a telephone survey by non-physicians. The questionnaire demonstrated good properties for discriminating patients with and without gout. It will be administered in a large sample of the general population to estimate the prevalence of gout in France. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Global Warming Estimation from MSU: Correction for Drift and Calibration Errors

NASA Technical Reports Server (NTRS)

Prabhakara, C.; Iacovazzi, R., Jr.; Yoo, J.-M.

2000-01-01

Microwave Sounding Unit (MSU) radiometer observations in Ch 2 (53.74 GHz), made in the nadir direction from sequential, sun-synchronous, polar-orbiting NOAA morning satellites (NOAA 6, 10 and 12 that have approximately 7am/7pm orbital geometry) and. afternoon satellites (NOAA 7, 9, 11 and 14 that have approximately 2am/2pm orbital geometry) are analyzed in this study to derive global temperature trend from 1980 to 1998. In order to remove the discontinuities between the data of the successive satellites and to get a continuous time series, first we have used shortest possible time record of each satellite. In this way we get a preliminary estimate of the global temperature trend of 0.21 K/decade. However, this estimate is affected by systematic time-dependent errors. One such error is the instrument calibration error eo. This error can be inferred whenever there are overlapping measurements made by two satellites over an extended period of time. From the available successive satellite data we have taken the longest possible time record of each satellite to form the time series during the period 1980 to 1998 to this error eo. We find eo can decrease the global temperature trend by approximately 0.07 K/decade. In addition there are systematic time dependent errors ed and ec present in the data that are introduced by the drift in the satellite orbital geometry. ed arises from the diurnal cycle in temperature and ec is the drift related change in the calibration of the MSU. In order to analyze the nature of these drift related errors the multi-satellite Ch 2 data set is partitioned into am and pm subsets to create two independent time series. The error ed can be assessed in the am and pm data of Ch 2 on land and can be eliminated. Observation made in the MSU Ch 1 (50.3 GHz) support this approach. The error ec is obvious only in the difference between the pm and am observations of Ch 2 over the ocean. We have followed two different paths to assess the impact of the error ec on the global temperature trend. In one path the entire error ec is placed in the am data while in the other it is placed in the pm data. Global temperature trend is increased or decreased by approximately 0.03 K/decade depending upon this placement. Taking into account all random errors and systematic errors our analysis of MSU observations leads us to conclude that a conservative estimate of the global warming is 0. 11 (+/-) 0.04 K/decade during 1980 to 1998.

Surfactant-mediated assembly of crystalline mesoporous aluminas: Synthesis, characterization, and application in hydrodesulfurization

NASA Astrophysics Data System (ADS)

Hicks, Randall Wayne

Aluminas are utilized in many industrial applications, including as adsorbents, abrasives, ceramics, catalysts, and catalyst supports. Many different phases of aluminas exist, but due to its favorable combination of surface and textural properties, the most important phase is gamma-alumina. Surface areas and pore volumes of conventional aluminas are typically less than 250 m 2/g and 0.5 cc/g, respectively. Performance in catalytic applications is limited in part by these properties. As has been shown in silica chemistry, the use of surfactants to aid in the assembly of a mesostructure leads to improvement in textural properties. Similar advances are anticipated in alumina chemistry, but to date, little progress has been made in this area. Since the disclosure of mesostructured aluminas in 1996, all but a couple of subsequent reports have described compositions of mesostructured aluminas with amorphous walls. This limits their thermal and hydrothermal stability, and thus their potential use in catalytic applications. The present work describes the synthesis of the first members of a new family of crystalline mesostructured aluminas prepared from the hydrolysis of aluminum sec-butoxide in the presence of either polyethylene oxide (PEO) or amine surfactants as porogens. Members of this family exhibiting the gamma-Al 2O3 phase, denoted MSU-gamma aluminas, have surface areas, pore sizes, and pore volumes in excess of 400 m2/g, 15 nm, and 1.5 cc/g, respectively. In addition, forms of these aluminas have expressed thermal and hydrothermal stability. Mesostructured boehmites, MSU-B aluminas, have also been obtained using similar synthetic methods. In the synthesis of either alumina, the key step is the formation of an MSU-S/B surfactant-boehmite precursor, which is converted to the desired final product through calcination. To demonstrate their usefulness, MSU-gamma aluminas have been utilized as catalyst supports in dibenzothiophene hydrodesulfurization reactions. Conversions and selectivities superior to that of a commercial catalyst have been achieved. Their success in this capacity can be traced to the stability of the gamma-Al 2O3 phase, the ability to effectively disperse the active catalytic component, and increased accessibility to the active sites.

Gout in Older Adults: The Atherosclerosis Risk in Communities Study

PubMed Central

Burke, Bridget Teevan; Köttgen, Anna; Law, Andrew; Grams, Morgan; Baer, Alan N.; Coresh, Josef

2016-01-01

Background: It is unclear whether traditional and genetic risk factors in middle age predict the onset of gout in older age. Methods: We studied the incidence of gout in older adults using the Atherosclerosis Risk in Communities study, a prospective U.S. population–based cohort of middle-aged adults enrolled between 1987 and 1989 with ongoing follow-up. A genetic urate score was formed from common urate-associated single nucleotide polymorphisms for eight genes. The adjusted hazard ratio and 95% confidence interval of incident gout by traditional and genetic risk factors in middle age were estimated using a Cox proportional hazards model. Results: The cumulative incidence from middle age to age 65 was 8.6% in men and 2.5% in women; by age 75 the cumulative incidence was 11.8% and 5.0%. In middle age, increased adiposity, beer intake, protein intake, smoking status, hypertension, diuretic use, and kidney function (but not sex) were associated with an increased gout risk in older age. In addition, a 100 µmol/L increase in genetic urate score was associated with a 3.29-fold (95% confidence interval: 1.63–6.63) increased gout risk in older age. Conclusions: These findings suggest that traditional and genetic risk factors in middle age may be useful for identifying those at risk of gout in older age. PMID:26714568

The kidney of chicken adapts to chronic metabolic acidosis: in vivo and in vitro studies.

PubMed

Craan, A G; Lemieux, G; Vinay, P; Gougoux, A

1982-08-01

Renal adaptation to chronic metabolic acidosis was studies in Arbor Acre hens receiving ammonium chloride by stomach tube 0.75 g/kg/day during 6 days. During a 14-day study, it was shown that the animals could excrete as much as 60% of the acid load during ammonium chloride administration. At the same time urate excretion fell markedly but the renal contribution to urate excretion (14%) did not change. During acidosis, blood glutamine increased twofold and the tissue concentration of glutamine rose in both liver and kidney. Infusion of L-glutamine led to increased ammonia excretion and more so in acidotic animals. Glutaminase I, glutamate dehydrogenase, alanine aminotransferase (GPT), and malic enzyme activities increased in the kidney during acidosis but phosphoenolpyruvate carboxykinase (PEPCK) activity did not change. Glutaminase I was not found in the liver, but hepatic glutamine synthetase rose markedly during acidosis. Glutamine synthetase was not found in the kidney. Renal tubules incubated with glutamine and alanine were ammoniagenic and gluconeogenic to the same degree as rat tubules with the same increments in acidosis. Lactate was gluconeogenic without increment during acidosis. The present study indicates that the avian kidney adapts to chronic metabolic acidosis with similarities and differences when compared to dog and rat. Glutamine originating from the liver appears to be the major ammoniagenic substrate. Our data also support the hypothesis that hepatic urate synthesis is decreased during acidosis.

The role of IL-1 in gout: from bench to bedside.

PubMed

So, Alexander; Dumusc, Alexandre; Nasi, Sonia

2018-01-01

The translation of our knowledge of the biology of MSU crystal-induced IL-1 secretion gives rise to new targets and therapeutic strategies in the treatment of acute gout. The NACHT, LRR and PYD domains-containing protein 3 inflammasome is key to this, and is the subject of intense research. Novel pathways that modulate inflammasome activation, reactive oxygen species generation and extracellular processing of IL-1 have been described and show promise in in vitro and animal studies. Meanwhile, blocking IL-1 by various IL-1 inhibitors has shown the validity of this concept. Patients with acute gout treated with these inhibitors showed positive clinical and biological responses. More work needs to be performed to assess the risk/benefit profile of anti-IL-1 therapies as well as to identify those who will benefit the most from this novel approach to the treatment of gout. © The Author 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Acute Gout Following Dermofasciectomy in a Patient With Dupuytren Disease.

PubMed

Cochrane, Elliott; Harper, Rosalyn

2017-01-01

A 62-year-old man underwent uncomplicated dermofasciectomy of the right little finger. In the week after surgery, he presented with erythema, tenderness, reduced range of movement, and a chalklike discharge from the suture line. Investigations revealed a raised serum urate level accompanied with a borderline rise in inflammatory markers. A diagnosis of acute gout was made. The patient was managed with nonsteroidal anti-inflammatory drugs. Clinicians should consider the diagnosis of gout when patients present after surgery with redness, pain, and swelling and also consider measuring urate levels before surgery and initiating colchicine prophylaxis when there is a known diagnosis of gout before surgery. Accurate diagnosis may prevent unnecessary antibiotic use. Copyright © 2017 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Allopurinol treatment and its effect on renal function in gout: a controlled study.

PubMed Central

Gibson, T; Rodgers, V; Potter, C; Simmonds, H A

1982-01-01

Fifty-nine patients with primary gout were treated with either a combination of colchicine and allopurinol or colchicine alone. Assessments of renal function over 2 years revealed a statistically significant fall of glomerular filtration rate an urine concentrating ability in those receiving only colchicine. The renal function of patients given allopurinol did not change. Treatment with allopurinol resulted ina significant reduction of ammonium excretion, a phenomenon which could not be readily explained. Urate clearance also declined during allopurinol treatment, and the impaired urate clearance associated with gout became more evident. The most important observation was that allopurinol retarded an apparent decline of renal function. Presumably this was achieved through its hypouricaemic effect and implies that the hyperuricaemia of gouty patients is deleterious to the kidneys. PMID:7039523

Renal function in urinary schistosomiasis in the Natal Province of South Africa.

PubMed

Coopan, R M; Naidoo, K; Jialal, I

1987-11-01

Renal function was assessed in 101 schoolchildren with active urinary schistosomiasis by measuring serum creatinine, urate, urea, and B2-microglobulin, urinary B2 microglobulin, and the glomerular filtration rate. Glomerular function in all subjects was normal as were serum creatinine, urate, and urea levels. Serum B2-microglobulin was elevated in only 8% of subjects while urinary B2-microglobulin only was raised in 7% of subjects, indicating proximal tubular dysfunction, a previously unreported feature in urinary schistosomiasis. Urinary tract abnormalities were found in 43% of subjects consenting to an excretory urogram but no correlation with biochemical parameters of renal function was noted. Serum angiotensin converting enzyme level measured in 70 subjects was elevated in 11% of subjects and was regarded as a possible measure of increased granulomatous activity.

2013 Montana Summer Transportation Institute.

DOT National Transportation Integrated Search

2013-10-01

The Summer Transportation Institute (STI) hosted by the Western Transportation Institute (WTI) at : Montana State University (MSU) aims to heighten student interest in transportation careers at the pre-college level. The program recruits high school ...

2014 Montana Summer Transportation Institute.

DOT National Transportation Integrated Search

2014-10-01

The Summer Transportation Institute (STI) hosted by the Western Transportation Institute (WTI) at : Montana State University (MSU) aims to heighten student interest in transportation careers at the pre-college level. The program recruits high school ...

2012 Montana Summer Transportation Institute

DOT National Transportation Integrated Search

2012-10-01

The Summer Transportation Institute (STI) hosted by the Western Transportation Institute (WTI) at Montana State University (MSU) aims to heighten student interest in transportation careers at the pre-college level. The program recruits high school st...

Neutral-current x-distributions

DOE R&D Accomplishments Database

Friedman, J. I.; Kendall, H. W.; Bogert, D.; Burnstein, R.; Fisk, R.; Fuess, S.; Bofill, J.; Busza, W.; Eldridge, T.; Abolins, M.; Brock, R.; et al.

1984-06-01

The role of the semi leptonic neutral current interaction as a probe of nucleon structure is examined. Previous measurements of neutral current x-distributions are reviewed, and new results from the Fermilab - MIT - MSU collaboration are presented.

The Student-to-Student Chemistry Initiative: Training High School Students To Perform Chemistry Demonstration Programs for Elementary School Students

NASA Astrophysics Data System (ADS)

Voegel, Phillip D.; Quashnock, Kathryn A.; Heil, Katrina M.

2004-05-01

The Student-to-Student Chemistry Initiative is an outreach program started in the fall of 2001 at Midwestern State University (MSU). The oncampus program trains high school science students to perform a series of chemistry demonstrations and subsequently provides kits containing necessary supplies and reagents for the high school students to perform demonstration programs at elementary schools. The program focuses on improving student perception of science. The program's impact on high school student perception is evaluated through statistical analysis of paired preparticipation and postparticipation surveys. The surveys focus on four areas of student perception: general attitude toward science, interest in careers in science, science awareness, and interest in attending MSU for postsecondary education. Increased scores were observed in all evaluation areas including a statistically significant increase in science awareness following participation.

Goddard Laboratory for Atmospheric Sciences physical retrieval system for remote determination of weather and climate parameter from HIRS2 and MSU observations

NASA Technical Reports Server (NTRS)

Susskind, J.

1984-01-01

At the Goddard Laboratory for Atmospheric Sciences (GLAS) a physically based satellite temperature sounding retrieval system, involving the simultaneous analysis of HIRS2 and MSU sounding data, was developed for determining atmospheric and surface conditions which are consistent with the observed radiances. In addition to determining accurate atmospheric temperature profiles even in the presence of cloud contamination, the system provides global estimates of day and night sea or land surface temperatures, snow and ice cover, and parameters related to cloud cover. Details of the system are described elsewhere. A brief overview of the system is presented, as well as recent improvements and previously unpublished results, relating to the sea-surface intercomparison workshop, the diurnal variation of ground temperatures, and forecast impact tests.

Investigation of Electron Transfer-Based Photonic and Electro-Optic Materials and Devices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bromenshenk, Jerry J; Abbott, Edwin H; Dickensheets, David

2008-03-28

Montana's state program began its sixth year in 2006. The project's research cluster focused on physical, chemical, and biological materials that exhibit unique electron-transfer properties. Our investigators have filed several patents and have also have established five spin-off businesses (3 MSU, 2 UM) and a research center (MT Tech). In addition, this project involved faculty and students at three campuses (MSU, UM, MT Tech) and has a number of under-represented students, including 10 women and 5 Native Americans. In 2006, there was an added emphasis on exporting seminars and speakers via the Internet from UM to Chief Dull Knife Communitymore » College, as well as work with the MT Department of Commerce to better educate our faculty regarding establishing small businesses, licensing and patent issues, and SBIR program opportunities.« less

An Algorithm to Generate Deep-Layer Temperatures from Microwave Satellite Observations for the Purpose of Monitoring Climate Change. Revised

NASA Technical Reports Server (NTRS)

Goldberg, Mitchell D.; Fleming, Henry E.

1994-01-01

An algorithm for generating deep-layer mean temperatures from satellite-observed microwave observations is presented. Unlike traditional temperature retrieval methods, this algorithm does not require a first guess temperature of the ambient atmosphere. By eliminating the first guess a potentially systematic source of error has been removed. The algorithm is expected to yield long-term records that are suitable for detecting small changes in climate. The atmospheric contribution to the deep-layer mean temperature is given by the averaging kernel. The algorithm computes the coefficients that will best approximate a desired averaging kernel from a linear combination of the satellite radiometer's weighting functions. The coefficients are then applied to the measurements to yield the deep-layer mean temperature. Three constraints were used in deriving the algorithm: (1) the sum of the coefficients must be one, (2) the noise of the product is minimized, and (3) the shape of the approximated averaging kernel is well-behaved. Note that a trade-off between constraints 2 and 3 is unavoidable. The algorithm can also be used to combine measurements from a future sensor (i.e., the 20-channel Advanced Microwave Sounding Unit (AMSU)) to yield the same averaging kernel as that based on an earlier sensor (i.e., the 4-channel Microwave Sounding Unit (MSU)). This will allow a time series of deep-layer mean temperatures based on MSU measurements to be continued with AMSU measurements. The AMSU is expected to replace the MSU in 1996.

Ammonium Fluoride Mediated Synthesis of Anhydrous Metal Fluoride-Mesoporous Carbon Nanocomposites for High-Performance Lithium Ion Battery Cathodes.

PubMed

Chun, Jinyoung; Jo, Changshin; Sahgong, Sunhye; Kim, Min Gyu; Lim, Eunho; Kim, Dong Hyeon; Hwang, Jongkook; Kang, Eunae; Ryu, Keun Ah; Jung, Yoon Seok; Kim, Youngsik; Lee, Jinwoo

2016-12-28

Metal fluorides (MF x ) are one of the most attractive cathode candidates for Li ion batteries (LIBs) due to their high conversion potentials with large capacities. However, only a limited number of synthetic methods, generally involving highly toxic or inaccessible reagents, currently exist, which has made it difficult to produce well-designed nanostructures suitable for cathodes; consequently, harnessing their potential cathodic properties has been a challenge. Herein, we report a new bottom-up synthetic method utilizing ammonium fluoride (NH 4 F) for the preparation of anhydrous MF x (CuF 2 , FeF 3 , and CoF 2 )/mesoporous carbon (MSU-F-C) nanocomposites, whereby a series of metal precursor nanoparticles preconfined in mesoporous carbon were readily converted to anhydrous MF x through simple heat treatment with NH 4 F under solventless conditions. We demonstrate the versatility, lower toxicity, and efficiency of this synthetic method and, using XRD analysis, propose a mechanism for the reaction. All MF x /MSU-F-C prepared in this study exhibited superior electrochemical performances, through conversion reactions, as the cathode for LIBs. In particular, FeF 3 /MSU-F-C maintained a capacity of 650 mAh g -1 FeF3 across 50 cycles, which is ∼90% of its initial capacity. We expect that this facile synthesis method will trigger further research into the development of various nanostructured MF x for use in energy storage and other applications.

An optimal ultrasonographic diagnostic test for early gout: A prospective controlled study

PubMed Central

Petraitis, Mykolas; Apanaviciene, Indre; Virviciute, Dalia; Baranauskaite, Asta

2017-01-01

Objective To identify the optimal sites for classification of early gout by ultrasonography. Methods Sixty patients with monosodium urate crystal-proven gout (25 with early gout [≤2-year symptom duration], 35 with late gout [>2-year symptom duration], and 36 normouricemic healthy controls) from one centre were prospectively evaluated. Standardized blinded ultrasound examination of 36 joints and the triceps and patellar tendons was performed to identify tophi and the double contour (DC) sign. Results Ultrasonographic sensitivity was lower in early than late gout. Binary logistic regression analysis showed that two ultrasonographic signs (tophi in the first metatarsophalangeal joint [odds ratio, 16.46] and the DC sign in the ankle [odds ratio, 25.18]) significantly contributed to the final model for early gout diagnosis (sensitivity and specificity of 84% and 81%, respectively). The inter-reader reliability kappa value for the DC sign and tophi was 0.712. Conclusions Four-joint investigation (both first metatarsophalangeal joints for tophi and both ankles for the DC sign) is feasible and reliable and could be proposed as a screening test for early ultrasonographic gout classification in daily practice. PMID:28617199

An optimal ultrasonographic diagnostic test for early gout: A prospective controlled study.

PubMed

Norkuviene, Eleonora; Petraitis, Mykolas; Apanaviciene, Indre; Virviciute, Dalia; Baranauskaite, Asta

2017-08-01

Objective To identify the optimal sites for classification of early gout by ultrasonography. Methods Sixty patients with monosodium urate crystal-proven gout (25 with early gout [≤2-year symptom duration], 35 with late gout [>2-year symptom duration], and 36 normouricemic healthy controls) from one centre were prospectively evaluated. Standardized blinded ultrasound examination of 36 joints and the triceps and patellar tendons was performed to identify tophi and the double contour (DC) sign. Results Ultrasonographic sensitivity was lower in early than late gout. Binary logistic regression analysis showed that two ultrasonographic signs (tophi in the first metatarsophalangeal joint [odds ratio, 16.46] and the DC sign in the ankle [odds ratio, 25.18]) significantly contributed to the final model for early gout diagnosis (sensitivity and specificity of 84% and 81%, respectively). The inter-reader reliability kappa value for the DC sign and tophi was 0.712. Conclusions Four-joint investigation (both first metatarsophalangeal joints for tophi and both ankles for the DC sign) is feasible and reliable and could be proposed as a screening test for early ultrasonographic gout classification in daily practice.

Febuxostat for the treatment of gout.

PubMed

Bridgeman, Mary Barna; Chavez, Benjamin

2015-02-01

Gout is a rheumatologic condition associated with elevated serum uric acid levels and deposition of monosodium urate crystals in joints and soft tissues. The xanthine oxidase inhibitor, allopurinol, has historically been the principle agent utilized for reducing elevated uric acid levels and treating underlying cause of gout symptoms; the availability of febuxostat, a newer non-purine selective xanthine oxidase inhibitor, represents an alternative therapy for those patients with contraindications or intolerance to allopurinol. This article reviews the published literature on the pharmacologic characteristics and clinical safety and efficacy data on the use of febuxostat in the treatment of gout. A literature search of MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations Databases (1996-November 2014) was conducted utilizing the key words 'febuxostat', 'allopurinol', and 'gout'. All published articles regarding febuxostat were evaluated. References of selected articles, data from poster presentations, and abstract publications were additionally reviewed. Febuxostat has shown benefit with respect to symptomatic relief and uric acid level reduction. The safety profile of this agent makes it an ideal alternative in those patients with contraindications to or who are intolerant of allopurinol.

Complex Analysis of Urate Transporters SLC2A9, SLC22A12 and Functional Characterization of Non-Synonymous Allelic Variants of GLUT9 in the Czech Population: No Evidence of Effect on Hyperuricemia and Gout

PubMed Central

Hurba, Olha; Mancikova, Andrea; Krylov, Vladimir; Pavlikova, Marketa; Pavelka, Karel; Stibůrková, Blanka

2014-01-01

Objective Using European descent Czech populations, we performed a study of SLC2A9 and SLC22A12 genes previously identified as being associated with serum uric acid concentrations and gout. This is the first study of the impact of non-synonymous allelic variants on the function of GLUT9 except for patients suffering from renal hypouricemia type 2. Methods The cohort consisted of 250 individuals (150 controls, 54 nonspecific hyperuricemics and 46 primary gout and/or hyperuricemia subjects). We analyzed 13 exons of SLC2A9 (GLUT9 variant 1 and GLUT9 variant 2) and 10 exons of SLC22A12 by PCR amplification and sequenced directly. Allelic variants were prepared and their urate uptake and subcellular localization were studied by Xenopus oocytes expression system. The functional studies were analyzed using the non-parametric Wilcoxon and Kruskall-Wallis tests; the association study used the Fisher exact test and linear regression approach. Results We identified a total of 52 sequence variants (12 unpublished). Eight non-synonymous allelic variants were found only in SLC2A9: rs6820230, rs2276961, rs144196049, rs112404957, rs73225891, rs16890979, rs3733591 and rs2280205. None of these variants showed any significant difference in the expression of GLUT9 and in urate transport. In the association study, eight variants showed a possible association with hyperuricemia. However, seven of these were in introns and the one exon located variant, rs7932775, did not show a statistically significant association with serum uric acid concentration. Conclusion Our results did not confirm any effect of SLC22A12 and SLC2A9 variants on serum uric acid concentration. Our complex approach using association analysis together with functional and immunohistochemical characterization of non-synonymous allelic variants did not show any influence on expression, subcellular localization and urate uptake of GLUT9. PMID:25268603

Evolutionary history and metabolic insights of ancient mammalian uricases

PubMed Central

Kratzer, James T.; Lanaspa, Miguel A.; Murphy, Michael N.; Cicerchi, Christina; Graves, Christina L.; Tipton, Peter A.; Ortlund, Eric A.; Johnson, Richard J.; Gaucher, Eric A.

2014-01-01

Uricase is an enzyme involved in purine catabolism and is found in all three domains of life. Curiously, uricase is not functional in some organisms despite its role in converting highly insoluble uric acid into 5-hydroxyisourate. Of particular interest is the observation that apes, including humans, cannot oxidize uric acid, and it appears that multiple, independent evolutionary events led to the silencing or pseudogenization of the uricase gene in ancestral apes. Various arguments have been made to suggest why natural selection would allow the accumulation of uric acid despite the physiological consequences of crystallized monosodium urate acutely causing liver/kidney damage or chronically causing gout. We have applied evolutionary models to understand the history of primate uricases by resurrecting ancestral mammalian intermediates before the pseudogenization events of this gene family. Resurrected proteins reveal that ancestral uricases have steadily decreased in activity since the last common ancestor of mammals gave rise to descendent primate lineages. We were also able to determine the 3D distribution of amino acid replacements as they accumulated during evolutionary history by crystallizing a mammalian uricase protein. Further, ancient and modern uricases were stably transfected into HepG2 liver cells to test one hypothesis that uricase pseudogenization allowed ancient frugivorous apes to rapidly convert fructose into fat. Finally, pharmacokinetics of an ancient uricase injected in rodents suggest that our integrated approach provides the foundation for an evolutionarily-engineered enzyme capable of treating gout and preventing tumor lysis syndrome in human patients. PMID:24550457

2015 Montana Summer Transportation Institute.

DOT National Transportation Integrated Search

2015-10-01

The Western Transportation Institute (WTI) at Montana State University (MSU) hosted a Summer : Transportation Institute (STI) from June 14 to June 26, 2015. The aim of the program is to introduce : high school participants to career opportunities in ...

Gout in Older Adults: The Atherosclerosis Risk in Communities Study.

PubMed

Burke, Bridget Teevan; Köttgen, Anna; Law, Andrew; Grams, Morgan; Baer, Alan N; Coresh, Josef; McAdams-DeMarco, Mara A

2016-04-01

It is unclear whether traditional and genetic risk factors in middle age predict the onset of gout in older age. We studied the incidence of gout in older adults using the Atherosclerosis Risk in Communities study, a prospective U.S. population-based cohort of middle-aged adults enrolled between 1987 and 1989 with ongoing follow-up. A genetic urate score was formed from common urate-associated single nucleotide polymorphisms for eight genes. The adjusted hazard ratio and 95% confidence interval of incident gout by traditional and genetic risk factors in middle age were estimated using a Cox proportional hazards model. The cumulative incidence from middle age to age 65 was 8.6% in men and 2.5% in women; by age 75 the cumulative incidence was 11.8% and 5.0%. In middle age, increased adiposity, beer intake, protein intake, smoking status, hypertension, diuretic use, and kidney function (but not sex) were associated with an increased gout risk in older age. In addition, a 100 µmol/L increase in genetic urate score was associated with a 3.29-fold (95% confidence interval: 1.63-6.63) increased gout risk in older age. These findings suggest that traditional and genetic risk factors in middle age may be useful for identifying those at risk of gout in older age. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The physiology of endothelial xanthine oxidase: from urate catabolism to reperfusion injury to inflammatory signal transduction.

PubMed

Meneshian, Avedis; Bulkley, Gregory B

2002-07-01

Xanthine oxidoreductase (XOR) is a ubiquitous metalloflavoprotein that appears in two interconvertible yet functionally distinct forms: xanthine dehydrogenase (XD), which is constitutively expressed in vivo; and xanthine oxidase (XO), which is generated by the posttranslational modification of XD, either through the reversible, incremental thiol oxidation of sulfhydryl residues on XD or the irreversible proteolytic cleavage of a segment of XD, which occurs at low oxygen tension and in the presence of several proinflammatory mediators. Functionally, both XD and XO catalyze the oxidation of purines to urate. However, whereas XD requires NAD+ as an electron acceptor for these redox reactions, thereby generating the stable product NADH, XO is unable to use NAD+ as an electron acceptor, requiring instead the reduction of molecular oxygen for this purine oxidation and generating the highly reactive superoxide free radical. Nearly 100 years of study has documented the physiologic role of XD in urate catabolism. However, the rapid, posttranslational conversion of XD to the oxidant-generating form XO provides a possible physiologic mechanism for rapid, posttranslational, oxidant-mediated signaling. XO-generated reactive oxygen species (ROS) have been implicated in various clinicopathologic entities, including ischemia/reperfusion injury and multisystem organ failure. More recently, the concept of physiologic signal transduction mediated by ROS has been proposed, and the possibility of XD to XO conversion, with subsequent ROS generation, serving as the trigger of the microvascular inflammatory response in vivo has been hypothesized. This review presents the evidence and basis for this hypothesis.

Dose range finding study for the efficacy of meloxicam administered prior to sodium urate-induced synovitis in cats.

PubMed

Carroll, Gwendolyn L; Narbe, Ruediger; Kerwin, Sharon C; Taylor, Lathrop; Peterson, Kurt; Hartsfield, Sandee M

2011-07-01

To determine the lowest efficacious dose of oral meloxicam for relieving pain in cats with a sodium urate (SU)-induced acute inflammatory synovitis. Randomized, blinded, controlled, and four-way crossover study. Eight surgically neutered cats (four males, four females) paired according to sex. Each pair of cats was treated with 0 (placebo), 0.025, 0.05, or 0.075 mg kg(-1) oral meloxicam once daily for 4 days prior to injection, into alternating stifles, of 1 mL of 20 mg mL(-1) SU crystals, beginning with the right stifle. Each cat received each of the four treatments, separated by at least 21 days. Analgesic efficacy was evaluated based on objective (e.g., pressure mat data total force, contact pressure, and contact area) and subjective (e.g., scores for Analgesia Scale [AS], Lameness Scale [LS], and Visual Analog Scale [VAS]) outcome measures for pain assessment. All outcome measures were recorded before and during 30 hours after SU injection. The pre-defined primary outcome measure was the area under the response-time curve (AUC(0-30) hours) of the total force of the injected limb. Data were analyzed by analysis of variance. A sequential test procedure was applied and the test sequence stopped in case of a nonsignificant result. Meloxicam at doses of 0.05 and 0.075 mg kg(-1) day(-1) PO was significantly different from placebo for the pre-defined primary outcome measure (i.e., AUC(0-30) hours of total force). All tested meloxicam doses were lower than placebo for the subjective outcome measures (i.e., AUC(0-30) hours of AS, LS, and VAS). The lowest efficacious dose of meloxicam for relieving pain in cats with an SU-induced synovitis was 0.05 mg kg(-1) day(-1) PO according to the pre-defined primary outcome measure. However, lower doses may also be effective as seen in the subjective outcome measures. © 2011 The Authors. Veterinary Anaesthesia and Analgesia. © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Shaping the Values of Youth: Sunday School Books in 19th Century America

Science.gov Websites

develop accessible digital/electronic collections, unfortunately, not all are. The MSU Libraries are able to provide remediated, accessible versions of digital/electronic library documents to library users

Flamelet Formation In Hele-Shaw Flow

NASA Technical Reports Server (NTRS)

Wichman, I. S.; Olson, S. L.

2003-01-01

A Hele-Shaw flow apparatus constructed at Michigan State University (MSU) produces conditions that reduce influences of buoyancy-driven flows. In addition, in the MSU Hele-Shaw apparatus it is possible to adjust the heat losses from the fuel sample (0.001 in. thick cellulose) and the flow speed of the approaching oxidizer flow (air) so that the "flamelet regime of flame spread" is entered. In this regime various features of the flame-to-smolder (and vice versa) transition can be studied. For the relatively wide (approx. 17.5 cm) and long (approx. 20 cm) samples used, approximately ten flamelets existed at all times. The flamelet behavior was studied mechanistically and statistically. A heat transfer analysis of the dominant heat transfer mechanisms was conducted. Results indicate that radiation and conduction processes are important, and that a simple 1-D model using the Broido-Shafizadeh model for cellulose decomposition chemistry can describe aspects of the flamelet spread process. Introduction

Success of Solar Dynamics Observatory (SDO) Education & Public Outreach (E/PO) in Montana

NASA Astrophysics Data System (ADS)

Freed, M. S.; Lowder, S. C.; McKenzie, D. E.

2013-03-01

The Space Public Outreach Team (SPOT) program at Montana State University (MSU) is the main component of SDO E/PO efforts in Montana. SPOT brings energetic presentations of recent science & NASA missions to students in primary & secondary schools. Presenters are university undergraduates that visit a diverse group of K-12 students from both rural & urban areas of Montana. This program is extremely cost effective, a valuable service-learning experience for undergraduates at MSU and has repeatedly received praise from both teachers and students. A complementary effort for training schoolteachers entitled NASA Education Activity Training (NEAT) is also employed. NEAT illustrates to teachers inexpensive and highly effective methods for demonstrating difficult science concepts to their students. We will highlight the successes and lessons learned from SPOT & NEAT, so that other E/PO programs can use it as a template to further science literacy in our nation's schools.

Utilization of the Internet to deliver educational materials to healthcare professionals.

PubMed

Hallgren, R C; Gorbis, S

1997-01-01

We have developed a computer-based learning module which uses three-dimensional animation sequences to enhance the acquisition of physical concepts and skills necessary for clinical evaluation and treatment of the cervical spine. This teaching tool, designed to serve as an adjunct to teaching strategies that faculty may be currently using, is available to students through the Kobiljak Resource Center at Michigan State University College of Osteopathic Medicine (MSUCOM) and via the Internet (http:/(/)hal.bim.msu.edu/EdTech) to individuals and groups who are physically removed from the MSU campus. While we are restricting this initial effort to the upper cervical spine, it is planned that future materials will include other parts of the body and, in addition, will enable students to not only visualize the effects of pathology on motion mechanics, but also give them the ability to interactively control an articulation in three-dimensional space.

The prediction of tropopause height from clusters of brightness temperatures and its application in the stratified regression temperature retrievals using microwave and infrared satellite measurements

NASA Technical Reports Server (NTRS)

Munteanu, M. J.; Piraino, P.; Jakubowicz, O.

1984-01-01

A total of 1575 radiosondes and the corresponding simulated brightness temperatures were used in an effort to derive a temperature retrieval based on the clusters of brightness temperatures. The 8 simulated channels, namely, 3 MSU and 5 IR of the TIROS-N satellite are used by the GLAS temperature retrieval method. The 3 MSU and 5 IR brightness temperatures were clustered into 17 cluster groups and a regression for the prediction of the tropopause height in mb was generated. The overall r.m.s. for the tropopause prediction is excellent, namely, around 16 mb for the summer and 23 mb for the winter. The correct cluster of brightness temperatures can be identified 98% of the time by the method of discriminatory classification if it is approximately a normal distribution or, in general, by the method of the nearest neighbor.

VizieR Online Data Catalog: Palomar/MSU and SDSS-DR7 M dwarfs with GALEX obs. (Jones+, 2016)

NASA Astrophysics Data System (ADS)

Jones, D. O.; West, A. A.

2016-03-01

To compare magnetic activity in the optical with UV activity, we matched the SDSS Data Release 7 (DR7; Abazajian et al. 2009, II/294) M dwarf spectroscopic catalog (West et al. 2011, J/AJ/141/97; R~2000) to GALEX data from Data Releases 6 and 7 (NUV: ~1750-2750Å and FUV: ~1350-1750Å; see II/312). The DR7 M dwarf catalog consists of 70841 SDSS M dwarfs with spectral types verified by eye. We supplemented the SDSS sample with the Palomar/MSU Nearby-Star Spectroscopic Survey (PMSU; Reid et al. 1995, III/198), which contains 1684 nearby low-mass stars (1415 M dwarfs) as part of the northern sample (δ>-30°) and 282 nearby low-mass stars (228 M dwarfs) as part of the southern sample. (2 data files).

MSuPDA: A memory efficient algorithm for sequence alignment.

PubMed

Khan, Mohammad Ibrahim; Kamal, Md Sarwar; Chowdhury, Linkon

2015-01-16

Space complexity is a million dollar question in DNA sequence alignments. In this regards, MSuPDA (Memory Saving under Pushdown Automata) can help to reduce the occupied spaces in computer memory. Our proposed process is that Anchor Seed (AS) will be selected from given data set of Nucleotides base pairs for local sequence alignment. Quick Splitting (QS) techniques will separate the Anchor Seed from all the DNA genome segments. Selected Anchor Seed will be placed to pushdown Automata's (PDA) input unit. Whole DNA genome segments will be placed into PDA's stack. Anchor Seed from input unit will be matched with the DNA genome segments from stack of PDA. Whatever matches, mismatches or Indel, of Nucleotides will be POP from the stack under the control of control unit of Pushdown Automata. During the POP operation on stack it will free the memory cell occupied by the Nucleotide base pair.

Quantitative two-dimensional gel electrophoresis analysis of human fibroblasts transformed by ras oncogenes.

PubMed

Miller, M J; Maher, V M; McCormick, J J

1992-11-01

Quantitative two-dimensional gel electrophoresis was used to compare the cellular protein patterns of a normal foreskin-derived human fibroblasts cell line (LG1) and three immortal derivatives of LG1. One derivative, designated MSU-1.1 VO, was selected for its ability to grow in the absence of serum and is non-tumorigenic in athymic mice. The other two strains were selected for focus-formation following transfection with either Ha-ras or N-ras oncogenes and form high grade malignant tumors. Correspondence and cluster analysis provided a nonbiased estimate of the relative similarity of the different two-dimensional patterns. These techniques separated the gel patterns into three distinct classes: LG1, MSU-1.1 VO, and the ras transformed cell strains. The MSU-1.1 VO cells were more closely related to the parental LG1 than to the ras-transformed cells. The differences between the three classes were primarily quantitative in nature: 16% of the spots demonstrated statistically significant changes (P < 0.01, T test, mean ratio of intensity > 2) in the rate of incorporation of radioactive amino acids. The patterns from the two ras-transformed cell strains were similar, and variations in the expression of proteins that occurred between the separate experiments obscured consistent differences between the Ha-ras and N-ras transformed cells. However, while only 9 out of 758 spots were classified as different (1%), correspondence analysis could consistently separate the two ras transformants. One of these spots was five times more intense in the Ha-ras transformed cells than the N-ras.(ABSTRACT TRUNCATED AT 250 WORDS)

21-cm Observations with the NASA ADAS 18-meter Antenna System: Baseline Astronomical Observations and Measurements of Performance Characteristics

NASA Astrophysics Data System (ADS)

Malphrus, B. K.; Combs, M. S.; Kruth, J.

2001-12-01

Herein we report astronomical observations made with the NASA Advanced Data Acquisition System (ADAS). The NASA ADAS antenna, located at NASA Goddard Spaceflight Center's Wallops Flight Facility, Virginia, is an 18-meter X-band antenna system that has been primarily used for satellite tracking and served as the telecommunication station for the NASA IUE satellite until ca. 1997. A joint NASA-Morehead State University (MSU)-Kentucky NSF EPSCoR venture has been initiated to upgrade and relocate the antenna system to MSU's Astrophysics Laboratory where it will provide a research instrument and active laboratory for undergraduate students as well as be engaged in satellite tracking missions. As part of the relocation efforts, many systems will be upgraded including replacement of a hydrostatic azimuth bearing with a high-precision electromechanical bearing, a new servo system, and Ku-capable reflector surface. It is widely believed that there are still contributions that small aperture centimeter-wave instruments can make utilizing three primary observing strategies: 1.) longitudinal studies of RF variations in cosmic phenomena, 2.) surveys of large areas of sky, and 3.) fast reactions to transient phenomena. MSU faculty and staff along with NASA engineers re-outfitted the ADAS system with RF systems and upgraded servo controllers during the spring and summer of 2001. Empirical measurements of primary system performance characteristics were made including G/T (at S- and L bands), noise figures, pointing and tracking accuracies, and drive speeds and accelerations. Baseline astronomical observations were made with the MSU L-band receiver using a 6 MHz bandwidth centered at 1420 MHz (21-cm) and observing over a range of frequencies (up to 2.5 MHz, tunable over the 6 MHz window) with a 2048-channel back-end spectrometer, providing up to 1 KHz frequency resolution. Baseline observations of radio sources herein reported include Cygnus A, 3C 157, 3C 48 and the Andromeda Galaxy. After its transition to Morehead State University (which is expected to be completed in 2004), the 18-meter will be available for use by students and faculty from all U.S. institutions for astronomical observations. Transitioning of the 18-meter antenna is made possible by NASA, and the Kentucky NSF EPSCoR program and by grants from the U.S. Small Business Administration.

Precision and Radiosonde Validation of Satellite Gridpoint Temperature Anomalies. Part II: A Tropospheric Retrieval and Trends during 1979-90.

NASA Astrophysics Data System (ADS)

Spencer, Roy W.; Christy, John R.

1992-08-01

TIROS-N satellite Microwave Sounding Unit (MSU) channel 2 data from different view angles across the MSU man swath are combined to remove the influence of the lower stratosphere and much of the upper troposphere on the measured brightness temperatures. The retrieval provides a sharper averaging kernel than the raw channel 2 weighting function, with a peak lowered from 50 kPa to 70 kPa and with only slightly more surface influence than raw channel 2. Monthly 2.5° gridpoint anomalies of this tropospheric retrieval compared between simultaneously operating satellites indicate close agreement, 0.15°C in the tropics to around 0.30°C over much of the higher latitudes. The agreement is not as close as with raw channel 2 anomalies because synoptic-scale temperature gradient information across the 2000-km swath of the MSU is lost in the retrieval procedure and because the retrieval involves the magnification of a small difference between two large numbers. Single gridpoint monthly anomaly correlations between the satellite measurements and the radiosonde calculations range from around 0.95 at high latitudes to below 0.8 in the tropical west Pacific, with standard errors of estimate of 0.16°C at Guam to around 0.50°C at high-latitude continental stations. Calculation of radiosonde temperature with a static weighting function instead of the radiative transfer equation degrades the standard errors by an average of less than 0.04°C. Of various standard tropospheric layers, the channel 2 retrieval anomalies correlate best with radiosonde 100-50- or 100-40-kPa-thickness anomalies. A comparison between global and hemispheric anomalies computed for raw channel 2 data versus the tropospheric retrieval show a correction in the 1979-90 time series for the volcano-induced stratospheric warming of 1982-83, which was independently observed by MSU channel 4. This correction leads to a slightly greater tropospheric warming trend in the 12-year time series (1979-90) for the tropospheric retrieval [0.039°C (±0.03°C) per decade] than for channel 2 alone [0.022°C (±0.02°C) per decade].

Analysis of canine urolith submissions to the Canadian Veterinary Urolith Centre, 1998-2014.

PubMed

Houston, Doreen M; Weese, Heather E; Vanstone, Nick P; Moore, Andrew E P; Weese, J Scott

2017-01-01

Understanding urolith trends and risk factors is important for understanding urolithiasis, which is a common problem in dogs. This study evaluated 75 674 canine cystolith submissions to the Canadian Veterinary Urolith Centre between 1998 and 2014. Struvite and calcium oxalate uroliths comprised 80.8% of all uroliths, with calcium oxalate outnumbering struvite. There were significant increases in the proportions of calcium oxalate, mixed and cystine uroliths, and significant decreases in struvite, urate, silica, and calcium phosphate carbonate over the study period. Breeds associated with increased risk of calcium oxalate urolithiasis tended to be small breeds, while those that were at increased risk of struvite urolith formation were larger breeds. Dalmatians were at increased risk of forming both urate and xanthine uroliths while Scottish deerhounds had a remarkably high association with cystine urolithiasis. Males were more likely to form calcium oxalate and metabolic uroliths and females were more likely to develop struvite and mixed uroliths.

Kidney lesions associated with mortality in chickens inoculated with waterfowl influenza viruses

USGS Publications Warehouse

Slemons, R.D.; Locke, L.N.; Sheerar, Martha G.; Duncan, R.M.; Hinshaw, Virginia S.; Easterday, B.C.

1990-01-01

Seventy-six type A influenza viruses recovered from waterfowl in Wisconsin, California, South Dakota, Florida, Texas, Alabama, and Nebraska were tested for virulence in chickens. The challenge to chickens was intravenous inoculation of first-, second-, or third-egg-passage virus. Each of the virus strains was tested separately in three or four chickens. Eighteen of the 76 viruses caused the death of one or more chickens following inoculation. Postmortem lesions were similar in all dead birds. In decreasing order of frequency, gross lesions included: swollen kidneys evident as accentuated lobular patterns, urates in the pericardial sac, and urates on the surface of the liver. Microscopic lesions present in kidneys were consistent with visceral gout. Mortality was associated with inoculations having higher concentrations of infectious virus. These results indicate that the influenza A viruses circulating in duck populations may include strains potentially pathogenic for chickens.

Final evaluation report for the greater Yellowstone regional traveler and weather information system (GYRTWIS)

DOT National Transportation Integrated Search

2004-12-30

This final report describes the national evaluation of the Greater Yellowstone Regional Traveler and Weather Information System (GYRTWIS). This evaluation complements the ongoing GYRTWIS evaluation being conducted by WTI/MSU by investigating three ar...

Evaluation of a Pharmacokinetic-Pharmacodynamic Model for Hypouricemic Effects of Febuxostat Using Datasets Obtained from Real-world Patients.

PubMed

Hirai, Toshinori; Itoh, Toshimasa; Kimura, Toshimi; Echizen, Hirotoshi

2018-06-06

Febuxostat is an active xanthine oxidase (XO) inhibitor that is widely used in the hyperuricemia treatment. We aimed to evaluate the predictive performance of a pharmacokinetic-pharmacodynamic (PK-PD) model for hypouricemic effects of febuxostat. Previously, we have formulated a PK--PD model for predicting hypouricemic effects of febuxostat as a function of baseline serum urate levels, body weight, renal function, and drug dose using datasets reported in preapproval studies (Hirai T et al., Biol Pharm Bull 2016; 39: 1013-21). Using an updated model with sensitivity analysis, we examined the predictive performance of the PK-PD model using datasets obtained from the medical records of patients who received febuxostat from March 2011 to December 2015 at Tokyo Women's Medical University Hospital. Multivariate regression analysis was performed to explore clinical variables to improve the predictive performance of the model. A total of 1,199 serum urate data were retrieved from 168 patients (age: 60.5 ±17.7 years, 71.4% males) who received febuxostat as hyperuricemia treatment. There was a significant correlation (r=0.68, p<0.01) between serum urate levels observed and those predicted by the modified PK-PD model. A multivariate regression analysis revealed that the predictive performance of the model may be improved further by considering comorbidities, such as diabetes mellitus, estimated glomerular filtration rate (eGFR), and co-administration of loop diuretics (r = 0.77, p<0.01). The PK-PD model may be useful for predicting individualized maintenance doses of febuxostat in real-world patients. This article is protected by copyright. All rights reserved.

Monitoring of Urate-Lowering Therapy Among US Veterans Following the 2012 American College of Rheumatology Guidelines for Management of Gout.

PubMed

Hughes, Jonathan C; Wallace, Jessica L; Bryant, Candace L; Salvig, Brent E; Fourakre, T Neal; Stone, William J

2017-04-01

With the prevalence of and hospitalizations for gout increasing, optimizing care for patients with gout is imperative. The 2012 American College of Rheumatology gout guidelines emphasize that timely monitoring is key to achieving serum urate (SUA) goals. Few studies have examined this metric following the 2012 update, and to our knowledge, none have examined a veteran population. To evaluate adherence to urate-lowering therapy (ULT) monitoring guidelines in a veteran population. This is a single-center, multisite, retrospective chart review of US veterans receiving ULT for gout within the VA (Veterans Affairs) Tennessee Valley Healthcare System from January 1, 2013, to June 30, 2015. The primary end point was percentage of patients with a SUA within 6 months of initial xanthine oxidase inhibitor prescription. Secondary end points included percentage of patients with SUA <6 mg/dL and percentage of patients with uptitration following SUA above goal. A total of 601 patients met inclusion criteria for the study; after application of exclusion criteria, 505 were analyzed. Of these, 295 patients (58%) did not have a SUA drawn within 6 months, and 162 patients (32%) reached the end of the study period without SUA measured. Of 226 patients with SUA above goal on initial check, 64 (28%) had timely dose adjustment, whereas 143 patients (63%) had no adjustment. A total of 161 patients (32%) had a SUA at goal within the study period. Rates of ULT monitoring at a major VA medical center were suboptimal, and improved adherence to guideline recommendations is needed.

Genetics of gout.

PubMed

Choi, Hyon K; Zhu, Yanyan; Mount, David B

2010-03-01

This review provides an update on recent findings with regards to the genetics of hyperuricemia and gout, including recent data from genome-wide association studies (GWAS). Five GWAS around the same time reported that genetic variants of SLC2A9/GLUT9 were associated with lower serum uric acid (SUA) levels and the effects were stronger among women (e.g. SUA level difference per copy of a minor allele, -0.46 mg/dl in women vs. -0.22 mg/dl in men). One study involving four cohorts and one meta-analysis of 14 genome-wide scans found that genetic variants of ABCG2 were associated with higher SUA concentrations and these effects were stronger among men (e.g. uric acid level difference per copy of the minor allele, 0.32 mg/dl in men vs. 0.18 mg/dl in women). Limited data indicate that these associations likely translate into those with the risk of gout. Functional determination that GLUT9 and ABCG2 can transport urate at the apical border of proximal tubules implicates them as substantial players in the renal excretion of urate. Furthermore, five novel genetic loci have been reported in the meta-analysis of 14 genome-wide scans. Combined with their activities as urate transporters and their strong associations with serum uric acid concentrations, GLUT9 and ABCG2 appeared to be important modulators of uric acid levels and likely of the risk of gout. Together with a growing list of environmental risk factors, these genetic data add considerably to our understanding of the pathogenesis of hyperuricemia and gout.

Cost-effectiveness of allopurinol and febuxostat for the management of gout.

PubMed

Jutkowitz, Eric; Choi, Hyon K; Pizzi, Laura T; Kuntz, Karen M

2014-11-04

Gout is the most common inflammatory arthritis in the United States. To evaluate the cost-effectiveness of urate-lowering treatment strategies for the management of gout. Markov model. Published literature and expert opinion. Patients for whom allopurinol or febuxostat is a suitable initial urate-lowering treatment. Lifetime. Health care payer. 5 urate-lowering treatment strategies were evaluated: no treatment; allopurinol- or febuxostat-only therapy; allopurinol-febuxostat sequential therapy; and febuxostat-allopurinol sequential therapy. Two dosing scenarios were investigated: fixed dose (80 mg of febuxostat daily, 0.80 success rate; 300 mg of allopurinol daily, 0.39 success rate) and dose escalation (≤120 mg of febuxostat daily, 0.82 success rate; ≤800 mg of allopurinol daily, 0.78 success rate). Discounted costs, discounted quality-adjusted life-years, and incremental cost-effectiveness ratios. In both dosing scenarios, allopurinol-only therapy was cost-saving. Dose-escalation allopurinol-febuxostat sequential therapy was more costly but more effective than dose-escalation allopurinol therapy, with an incremental cost-effectiveness ratio of $39 400 per quality-adjusted life-year. The relative rankings of treatments did not change. Our results were relatively sensitive to several potential variations of model assumptions; however, the cost-effectiveness ratios of dose escalation with allopurinol-febuxostat sequential therapy remained lower than the willingness-to-pay threshold of $109 000 per quality-adjusted life-year. Long-term outcome data for patients with gout, including medication adherence, are limited. Allopurinol single therapy is cost-saving compared with no treatment. Dose-escalation allopurinol-febuxostat sequential therapy is cost-effective compared with accepted willingness-to-pay thresholds. Agency for Healthcare Research and Quality.

Efficacy and safety of febuxostat in elderly female patients.

PubMed

Mizuno, Tomohiro; Hayashi, Takahiro; Hikosaka, Sayo; Shimabukuro, Yuka; Murase, Maho; Takahashi, Kazuo; Hayashi, Hiroki; Yuzawa, Yukio; Nagamatsu, Tadashi; Yamada, Shigeki

2014-01-01

Maintenance of low serum urate levels is important for the management of gout. Achieving the recommended serum urate levels of less than 6.0 mg/dL is difficult in elderly (65 years of age or older) patients with renal impairment. Xanthine oxidase inhibitors allopurinol and febuxostat are used for this purpose. Although febuxostat had been shown to be efficacious in elderly patients, its safety and efficacy in elderly female patients with hyperuricemia remain unclear. The aim of this study was to assess the efficacy and safety of febuxostat in elderly female patients. We studied a retrospective cohort study. The study included elderly Japanese patients (65 years of age or older) who were treated with febuxostat at Fujita Health University Hospital from January 2012 to December 2013. The treatment goal was defined as achievement of serum urate levels of 6.0 mg/dL or lower within 16 weeks; this was the primary endpoint in the present study. Adverse events of febuxostat were defined as more than twofold increases in Common Terminology Criteria for adverse events scores from baseline. We evaluated 82 patients treated with febuxostat during the observation period and classified them into male (n=53) and female (n=29) groups. The mean time to achievement of the treatment goal was significantly shorter in the female group (53 days) than in the male group (71 days). There were no significant differences in adverse events between the 2 groups. Our findings suggest that the efficacy of febuxostat in elderly female patients is superior to that in elderly male patients and that the safety is equivalent.

Role of nitrite, urate and pepsin in the gastroprotective effects of saliva

PubMed Central

Rocha, Bárbara S.; Lundberg, Jon O; Radi, Rafael; Laranjinha, João

2016-01-01

Dietary nitrate is now recognized as an alternative substrate for nitric oxide (•NO) production in the gut. This novel pathway implies the sequential reduction of nitrate to nitrite, •NO and other bioactive nitrogen oxides but the physiological relevance of these oxidants has remained elusive. We have previously shown that dietary nitrite fuels an hitherto unrecognized nitrating pathway at acidic gastric pH, through which pepsinogen is nitrated in the gastric mucosa, yielding a less active form of pepsin in vitro. Here, we demonstrate that pepsin is nitrated in vivo and explore the functional impact of protein nitration by means of peptic ulcer development. Upon administration of pentagastrin and human nitrite-rich saliva or sodium nitrite to rats, nitrated pepsin was detected in the animal's stomach by immunoprecipitation. •NO was measured in the gastric headspace before and after nitrite instillation by chemiluminescence. At the end of each procedure, the stomach's lesions, ranging from gastric erosions to haemorrhagic ulcers, were scored. Nitrite increased gastric •NO by 200-fold (p<0.05) and nitrated pepsin was detected both in the gastric juice and the mucosa (p<0.05). Exogenous urate, a scavenger of nitrogen dioxide radical, blunted •NO detection and inhibited pepsin nitration, suggesting an underlining free radical-dependent mechanism for nitration. Functionally, pepsin nitration prevented the development of gastric ulcers, as the lesions were only apparent when pepsin nitration was inhibited by urate. In sum, this work unravels a novel dietary-dependent nitrating pathway in which pepsin is nitrated and inactivated in the stomach, preventing the progression of gastric ulcers. PMID:27156250

Comparative semiempirical and ab initio study of the structural and chemical properties of uric acid and its anions

NASA Astrophysics Data System (ADS)

Altarsha, Muhannad; Monard, Gérald; Castro, Bertrand

Semiempirical, density functional theory (DFT), and ab initio calculations have been performed to assess the relative stabilities of 15 possible tautomer forms of neutral uric acid, and of the different urate mono- and dianion forms. These methods have also been used to compute ionization potentials (IPs) for uric acid and its derived anions. Overall, we have found that semiempirical calculations, in particular PM3, perform well as compared with B3LYP or MP2 computations toward these different structural and chemical properties of uric acid: the triketo form of uric acid is the most stable tautomer form of neutral uric acid. Three other tautomer forms are relatively close in energy, within the range 2-6 kcal/mol above the triketo form, with a mean energy deviation of only 1.3 kcal/mol between PM3 and DFT or ab initio results; the monoanion form of uric acid obtained by abstracting one proton in position 3 (denoted UAN3-) is the most stable form among all four possible urate monoanions both in gas phase and in solution; the dianion form of uric acid obtained by abstracting two protons, respectively, in positions 3 and 9 of uric acid (denoted UAN3-N9-) is the most stable urate dianion form both in gas phase and in solution. However, these two most stable species do not have the lowest IPs in solution: among monoanions and dianions, respectively, the species with the lowest IPs are UAN7- and UAN7-N9-.

Urate oxidase for the prevention and treatment of tumour lysis syndrome in children with cancer.

PubMed

Cheuk, Daniel Kl; Chiang, Alan Ks; Chan, Godfrey Cf; Ha, Shau Yin

2017-03-08

Tumour lysis syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Previous reviews did not find clear evidence of benefit of urate oxidase in children with cancer. This review is the second update of a previously published Cochrane review. To assess the effects and safety of urate oxidase for the prevention and treatment of TLS in children with malignancies. In March 2016 we searched CENTRAL, MEDLINE, Embase, and CINAHL. In addition, we searched the reference lists of all identified relevant papers, trials registers and other databases. We also screened conference proceedings and we contacted experts in the field and the manufacturer of rasburicase, Sanofi-aventis. Randomised controlled trials (RCT) and controlled clinical trials (CCT) of urate oxidase for the prevention or treatment of TLS in children under 18 years with any malignancy. Two review authors independently extracted trial data and assessed individual trial quality. We used risk ratios (RR) for dichotomous data and mean difference (MD) for continuous data. We included seven trials, involving 471 participants in the treatment groups and 603 participants in the control groups. No new studies were identified in the update. One RCT and five CCTs compared urate oxidase and allopurinol. Three trials tested Uricozyme, and three trials tested rasburicase for the prevention of TLS.The RCT did not evaluate the primary outcome (incidence of clinical TLS). It showed no clear evidence of a difference in mortality (both all-cause mortality (Fisher's exact test P = 0.23) and mortality due to TLS (no deaths in either group)), renal failure (Fisher's exact test P = 0.46), and adverse effects between the treatment and the control groups (Fisher's exact test P = 1.0). The frequency of normalisation of uric acid at four hours (10 out of 10 participants in the treatment group versus zero out of nine participants in the control group, Fisher's exact test P < 0.001) and area under the curve of uric acid at four days (MD -201.00 mg/dLhr, 95% CI -258.05 mg/dLhr to -143.95 mg/dLhr; P < 0.00001) were significantly better in the treatment group.One CCT evaluated the primary outcome; no clear evidence of a difference was identified between the treatment and the control groups (RR 0.77, 95% CI 0.44 to 1.33; P = 0.34). Pooled results of three CCTs showed significantly lower mortality due to TLS in the treatment group (RR 0.05, 95% CI 0.00 to 0.89; P = 0.04); no clear evidence of a difference in all-cause mortality was identified between the groups (RR 0.19, 95% CI 0.01 to 3.42; P = 0.26). Pooled results from five CCTs showed significantly lower incidence of renal failure in the treatment group (RR 0.26, 95% CI 0.08 to 0.89; P = 0.03). Results of CCTs also showed significantly lower uric acid in the treatment group at two days (three CCTs: MD -3.80 mg/dL, 95% CI -7.37 mg/dL to -0.24 mg/dL; P = 0.04), three days (two CCTs: MD -3.13 mg/dL, 95% CI -6.12 mg/dL to -0.14 mg/dL; P = 0.04), four days (two CCTs: MD -4.60 mg/dL, 95% CI -6.39 mg/dL to -2.81 mg/dL; P < 0.00001), and seven days (one CCT: MD -1.74 mg/dL, 95% CI -3.01 mg/dL to -0.47 mg/dL; P = 0.007) after therapy, but not one day (three CCTs: MD -3.00 mg/dL, 95% CI -7.61 mg/dL to 1.60 mg/dL; P = 0.2), five days (one CCT: MD -1.02 mg/dL, 95% CI -2.24 mg/dL to 0.20 mg/dL; P = 0.1), and 12 days (one CCT: MD -0.80 mg/dL, 95% CI -2.51 mg/dL to 0.91 mg/dL; P = 0.36) after therapy. Pooled results from three CCTs showed higher frequency of adverse effects in participants who received urate oxidase (RR 9.10, 95% CI 1.29 to 64.00; P = 0.03).Another included RCT, with 30 participants, compared different doses of rasburicase (0.2 mg/kg versus 0.15 mg/kg). The primary outcome was not evaluated. No clear evidence of a difference in mortality (all-cause mortality (Fisher's exact test P = 1.0) and mortality due to TLS (no deaths in both groups)) and renal failure (no renal failure in both groups) was identified. It demonstrated no clear evidence of a difference in uric acid normalisation (RR 1.07, 95% CI 0.89 to 1.28; P = 0.49) and uric acid level at four hours (MD 8.10%, 95% CI -0.99% to 17.19%; P = 0.08). Common adverse events of urate oxidase included hypersensitivity, haemolysis, and anaemia, but no clear evidence of a difference between treatment groups was identified (RR 0.54, 95% CI 0.12 to 2.48; P = 0.42).The quality of evidence ranks from very low to low because of imprecise results, and all included trials were highly susceptible to biases. Although urate oxidase might be effective in reducing serum uric acid, it is unclear whether it reduces clinical TLS, renal failure, or mortality. Adverse effects might be more common for urate oxidase compared with allopurinol. Clinicians should weigh the potential benefits of reducing uric acid and uncertain benefits of preventing mortality or renal failure from TLS against the potential risk of adverse effects.

The effect of ego-motion on environmental monitoring.

PubMed

Lerner, Uri; Yacobi, Tamar; Levy, Ilan; Moltchanov, Sharon A; Cole-Hunter, Tom; Fishbain, Barak

2015-11-15

Air pollution has a proven impact on public health. Currently, pollutant levels are obtained by high-priced, sizeable, stationary Air Quality Monitoring (AQM) stations. Recent developments in sensory and communication technologies have made relatively low-cost, micro-sensing units (MSUs) feasible. Their lower power consumption and small size enable mobile sensing, deploying single or multiple units simultaneously. Recent studies have reported on measurements acquired by mobile MSUs, mounted on cars, bicycles and pedestrians. While these modes of transportation inherently present different velocity and acceleration regimes, the effect of the sensors' varying movement characteristics have not been previously accounted for. This research assesses the impact of sensor's motion on its functionality through laboratory measurements and a field campaign. The laboratory setup consists of a wind tunnel to assess the effect of air flow on the measurements of nitrogen dioxide and ozone at different velocities in a controlled environment, while the field campaign is based on three cars mounted with MSUs, measuring pollutants and environmental variables at different traveling speeds. In both experimental designs we can regard the MSUs as a moving object in the environment, i.e. having a distinct ego-motion. The results show that MSU's behavior is highly affected by variation in speed and sensor placement with respect to direction of movement, mainly due to the physical properties of installed sensors. This strongly suggests that any future design of MSU must account for the speed effect from the design stage all the way through deployment and results analysis. This is the first report examining the influence of airflow variations on MSU's ability to accurately measure pollutant levels. Copyright © 2015 Elsevier B.V. All rights reserved.

Proceedings of the XXI International Workshop High Energy Physics and Quantum Field Theory (QFTHEP 2013). 23 30 June, 2013. Saint Petersburg Area, Russia

NASA Astrophysics Data System (ADS)

The Workshop continues a series of workshops started by the Skobeltsyn Institute of Nuclear Physics of Lomonosov Moscow State University (SINP MSU) in 1985 and conceived with the purpose of presenting topics of current interest and providing a stimulating environment for scientific discussion on new developments in theoretical and experimental high energy physics and physical programs for future colliders. Traditionally the list of workshop attendees includes a great number of active young scientists and students from Russia and other countries. This year the Workshop is organized jointly by the SINP MSU and the SPbSU and it will take place in the holiday hotel "Baltiets" situated in a picturesque place of the Karelian Isthmus on the shore of the Gulf of Finland in the suburb of the second largest Russian city Saint Petersburg. Scientific program, the main topics to be covered are: * Higgs searches and other experimental results from the LHC and the Tevatron; impact of the Higgs-like boson observed * Physics prospects at Linear Colliders and super B-factories * Extensions of the Standard Model and their phenomenological consequences at the LHC and Linear Colliders * Higher order corrections and resummations for collider phenomenology * Automatic calculations and Monte Carlo simulations in high energy physics * LHC/LC and astroparticle/cosmology connections * Modern nuclear physics and relativistic nucleous-nucleous collisions * Detectors for future experiments in high energy physics The Workshop will include plenary and two parallel afternoon sessions. The plenary sessions will consist of invited lectures. The afternoon sessions will include original talks. Further details are given at http://qfthep.sinp.msu.ru

METAL MEDIA FILTERS, AG-1 SECTION FI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adamson, D.

One application of metal media filters is in various nuclear air cleaning processes including applications for protecting workers, the public and the environment from hazardous and radioactive particles. To support this application the development of the ASME AG-1 FI Standard on Metal Media has been under way for more than ten years. Development of the proposed section has required resolving several difficult issues associated with operating conditions (media velocity, pressure drop, etc.), qualification testing, and quality acceptance testing. Performance characteristics of metal media are dramatically different than the glass fiber media with respect to parameters like differential pressures, operating temperatures,more » media strength, etc. These differences make existing data for a glass fiber media inadequate for qualifying a metal media filter for AG-1. In the past much work has been conducted on metal media filters at facilities such as Lawrence Livermore National Laboratory (LLNL) and Savannah River National Laboratory (SRNL) to qualify the media as High Efficiency Particulate Air (HEPA) Filters. Particle retention testing has been conducted at Oak Ridge Filter Test Facility and at Air Techniques International (ATI) to prove that the metal media meets or exceeds the 99.97% particle retention required for a HEPA Filter. Even with his testing, data was lacking to complete an AG-1 FI Standard on metal media. With funding secured by Mississippi State University (MSU) from National Nuclear Security Administration (NNSA), a research test stand is being designed and fabricated at MSU's Institute for Clean Energy Technology (ICET) Facility to obtain qualification data on metal media. This in turn will support required data needed for the FI Standard. The paper will discuss in detail how the test stand at MSU will obtain the necessary data to complete the FI Standard.« less

Inflammatory Role of Macrophage Xanthine Oxidoreductase in Pulmonary Hypertension: Implications for Novel Therapeutic Approaches

DTIC Science & Technology

2015-10-01

Lung Inflammation, Uric Acid, Chronic Obstructive Pulmonary Disease, Mononuclear Phagocyte , Monosodium Urate, XOR WT, XOR KO, Wistar Kyoto, Pulmonary...0451 Annual Report (Year 1) 4 Mononuclear Phagocyte XOR Activity and Superoxide Generation Were Reduced by

Diagnosis of Acute Gout: A Clinical Practice Guideline From the American College of Physicians.

PubMed

Qaseem, Amir; McLean, Robert M; Starkey, Melissa; Forciea, Mary Ann

2017-01-03

The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the diagnosis of gout. This guideline is based on a systematic review of published studies on gout diagnosis, identified using several databases, from database inception to February 2016. Evaluated outcomes included the accuracy of the test results; intermediate outcomes (results of laboratory and radiographic tests, such as serum urate and synovial fluid crystal analysis and radiographic or ultrasonography changes); clinical decision making (additional testing and pharmacologic or dietary management); short-term clinical (patient-centered) outcomes, such as pain and joint swelling and tenderness; and adverse effects of the tests. This guideline grades the evidence and recommendations by using the ACP grading system, which is based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. The target audience for this guideline includes all clinicians, and the target patient population includes adults with joint inflammation suspected to be gout. ACP recommends that clinicians use synovial fluid analysis when clinical judgment indicates that diagnostic testing is necessary in patients with possible acute gout. (Grade: weak recommendation, low-quality evidence).

Education Needs of Michigan Farmers

ERIC Educational Resources Information Center

Suvedi, Murari; Jeong, Eunseong; Coombs, John

2010-01-01

In 2008 MSU Extension evaluated their program to identify the major areas of educational need for Michigan farmers and agribusiness operators. Surveys were mailed to a stratified random sample from Michigan Agricultural Statistics Service records of dairy, livestock, swine, cash crops, fruit, vegetable, and nursery/greenhouse producers. Findings…

76 FR 27914 - Television Broadcasting Services; Kalispell, MT

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-13

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 73 [MB Docket No. 11-20; RM-11619, DA 11-750] Television Broadcasting Services; Kalispell, MT AGENCY: Federal Communications Commission. ACTION: Final rule... rulemaking filed by Montana State University (``MSU'') requesting that channel *46 be transferred from the...

Biochemical profile of stone-forming patients with diabetes mellitus.

PubMed

Pak, Charles Y C; Sakhaee, Khashayar; Moe, Orson; Preminger, Glenn M; Poindexter, John R; Peterson, Roy D; Pietrow, Paul; Ekeruo, Wesley

2003-03-01

To test the hypothesis that stone-forming patients with type II diabetes (DM-II) have a high prevalence of uric acid (UA) stones and present with some of the biochemical features of gouty diathesis (GD). The demographic and initial biochemical data from 59 stone-forming patients with DM-II (serum glucose greater than 126 mg/dL, no insulin therapy, older than 35 years of age) from Dallas, Texas and Durham, North Carolina were retrieved and compared with data from 58 patients with GD and 116 with hyperuricosuric calcium oxalate urolithiasis (HUCU) without DM. UA stones were detected in 33.9% of patients with DM-II compared with 6.2% of stone-forming patients without DM (P <0.001). Despite similar ingestion of alkali, the urinary pH in patients with DM-II and UA stones (n = 20) was low (pH = 5.5), as it is in patients with GD, and was significantly lower than in patients with HUCU. The urinary pH in patients with DM-II and calcium stones (n = 39) was intermediate between that in those with DM-II and UA stones and those with HUCU. However, both DM groups had fractional excretion of urate that was not depressed, as it is in those with GD, and was comparable to the value obtained in those with HUCU. The urinary content of undissociated UA was significantly higher, and the saturation of calcium phosphate (brushite) and sodium urate was significantly lower in those with DM-II and UA stones than in those with HUCU. Stone-forming patients with DM-II have a high prevalence of UA stones. Diabetic patients with UA stones share a key feature of those with GD, namely the passage of unusually acid urine, but not the low fractional excretion of urate.

A phase 3, multicenter, randomized, allopurinol-controlled study assessing the safety and efficacy of oral febuxostat in Chinese gout patients with hyperuricemia.

PubMed

Xu, Shaoyong; Liu, Xiangyang; Ming, Jie; Chen, Shenren; Wang, Yangang; Liu, Xiumei; Liu, Hong; Peng, Yongde; Wang, Jianqin; Lin, Jinying; Ji, Haiwang; Liu, Bin; Lu, Ying; Liu, Peng; Zhang, Yonghong; Ji, Qiuhe

2015-07-01

To compare the efficiency and safety of febuxostat with those of allopurinol in Chinese patients with gout and hyperuricemia. The trial which was conducted at 13 centers in China during 2011-2013 included a 2-week run-in and a 24-week treatment period. A total of 504 eligible participants with gout and with serum urate ≥ 480 μmol/L were randomly assigned 1 : 1 : 1 to febuxostat 40 mg/day, febuxostat 80 mg/day and allopurinol 300 mg/day groups. The primary efficacy endpoint was the percentage of subjects whose last three serum urate levels were < 360 μmol/L. The primary efficacy endpoint was reached by 33.5% of subjects taking febuxostat 80 mg/day, 22.5% of those taking febuxostat 40 mg/day and 17.0% of those taking allopurinol 300 mg/day (P < 0.001 for the comparison between febuxostat 80 mg/day and allopurinol 300 mg/day groups; P = 0.216 for the comparison between febuxostat 40 mg/day and allopurinol 300 mg/day groups). The incidence of gout flare was relatively high in each group during the first 8 weeks and gradually decreased thereafter. There was no statistically significant difference between the three groups (P > 0.05). The incidence of adverse events was similar in the three treatment groups. The most frequent treatment-related adverse events were liver function test abnormalities. Febuxostat 80 mg/day had superior urate-lowering efficacy to that of febuxostat 40 mg/day or allopurinol 300 mg/day, which was comparable in Chinese gout patients with hyperuricemia. Febuxostat, at a daily dose of 40 or 80 mg, was safe and well tolerated. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Diabetes and gout: efficacy and safety of febuxostat and allopurinol.

PubMed

Becker, M A; MacDonald, P A; Hunt, B J; Jackson, R L

2013-11-01

Assess influences of demographics and co-morbidities of gout patients with or without diabetes on safety and efficacy of urate-lowering agents. Post-hoc analysis of 312 diabetic and 1957 non-diabetic gout patients [baseline serum urate levels (sUA) ≥8.0 mg/dl] enrolled in a 6-month randomized controlled trial comparing urate-lowering efficacy (ULE) and safety of daily xanthine oxidase inhibitors (XOIs) febuxostat (40 mg or 80 mg) and allopurinol (200 mg or 300 mg). We compared baseline demographic, gout and co-morbid characteristics, ULE, and safety of XOI treatment in diabetic and non-diabetic gout patients. ULE was measured by the proportion of diabetic and non-diabetic patients in each treatment group achieving final visit sUA < 6.0 mg/dl. Safety was monitored throughout the trial. Diabetic gout patients were older, more frequently female, and had longer gout duration. Co-morbidities were more frequent among diabetic patients: cardiovascular disease; impaired renal function; hyperlipidemia; and obesity (body mass index >30 kg/m²) (p < 0.001 for all comparisons). Febuxostat 80 mg ULE exceeded that of febuxostat 40 mg or allopurinol (p < 0.050) at all levels of renal function, achieving sUA goal range in the majority of diabetic and non-diabetic patients. Diabetics and non-diabetics reported self-limiting diarrhoea and URIs as the most common adverse events. Despite higher co-morbidity rates in diabetic patients, febuxostat and allopurinol were safe in both groups at the doses tested. Febuxostat 80 mg achieved sUA <6.0 mg/dl more often than febuxostat 40 mg or allopurinol at commonly prescribed doses. © 2013 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Diabetes and gout: efficacy and safety of febuxostat and allopurinol

PubMed Central

Becker, M A; MacDonald, P A; Hunt, B J; Jackson, R L

2013-01-01

Aim Assess influences of demographics and co-morbidities of gout patients with or without diabetes on safety and efficacy of urate-lowering agents. Methods Post-hoc analysis of 312 diabetic and 1957 non-diabetic gout patients [baseline serum urate levels (sUA) ≥8.0 mg/dl] enrolled in a 6-month randomized controlled trial comparing urate-lowering efficacy (ULE) and safety of daily xanthine oxidase inhibitors (XOIs) febuxostat (40 mg or 80 mg) and allopurinol (200 mg or 300 mg). We compared baseline demographic, gout and co-morbid characteristics, ULE, and safety of XOI treatment in diabetic and non-diabetic gout patients. ULE was measured by the proportion of diabetic and non-diabetic patients in each treatment group achieving final visit sUA < 6.0 mg/dl. Safety was monitored throughout the trial. Results Diabetic gout patients were older, more frequently female, and had longer gout duration. Co-morbidities were more frequent among diabetic patients: cardiovascular disease; impaired renal function; hyperlipidemia; and obesity (body mass index >30 kg/m2) (p < 0.001 for all comparisons). Febuxostat 80 mg ULE exceeded that of febuxostat 40 mg or allopurinol (p < 0.050) at all levels of renal function, achieving sUA goal range in the majority of diabetic and non-diabetic patients. Diabetics and non-diabetics reported self-limiting diarrhoea and URIs as the most common adverse events. Conclusions Despite higher co-morbidity rates in diabetic patients, febuxostat and allopurinol were safe in both groups at the doses tested. Febuxostat 80 mg achieved sUA <6.0 mg/dl more often than febuxostat 40 mg or allopurinol at commonly prescribed doses. PMID:23683134

Efficacy and safety of febuxostat in elderly female patients

PubMed Central

Mizuno, Tomohiro; Hayashi, Takahiro; Hikosaka, Sayo; Shimabukuro, Yuka; Murase, Maho; Takahashi, Kazuo; Hayashi, Hiroki; Yuzawa, Yukio; Nagamatsu, Tadashi; Yamada, Shigeki

2014-01-01

Background Maintenance of low serum urate levels is important for the management of gout. Achieving the recommended serum urate levels of less than 6.0 mg/dL is difficult in elderly (65 years of age or older) patients with renal impairment. Xanthine oxidase inhibitors allopurinol and febuxostat are used for this purpose. Although febuxostat had been shown to be efficacious in elderly patients, its safety and efficacy in elderly female patients with hyperuricemia remain unclear. Objective The aim of this study was to assess the efficacy and safety of febuxostat in elderly female patients. Methods We studied a retrospective cohort study. The study included elderly Japanese patients (65 years of age or older) who were treated with febuxostat at Fujita Health University Hospital from January 2012 to December 2013. The treatment goal was defined as achievement of serum urate levels of 6.0 mg/dL or lower within 16 weeks; this was the primary endpoint in the present study. Adverse events of febuxostat were defined as more than twofold increases in Common Terminology Criteria for adverse events scores from baseline. Results We evaluated 82 patients treated with febuxostat during the observation period and classified them into male (n=53) and female (n=29) groups. The mean time to achievement of the treatment goal was significantly shorter in the female group (53 days) than in the male group (71 days). There were no significant differences in adverse events between the 2 groups. Conclusion Our findings suggest that the efficacy of febuxostat in elderly female patients is superior to that in elderly male patients and that the safety is equivalent. PMID:25214776

Population pharmacokinetics and exposure-uric acid analyses after single and multiple doses of ABT-639, a calcium channel blocker, in healthy volunteers.

PubMed

An, Guohua; Liu, Wei; Duan, W Rachel; Nothaft, Wolfram; Awni, Walid; Dutta, Sandeep

2015-03-01

ABT-639 is a selective T-type calcium channel blocker with efficacy in a wide range of preclinical models of nociceptive and neuropathic pain. In the current first-in-human (FIH) study, the pharmacokinetics, tolerability, and safety of ABT-639 after single- (up to 170 mg) and multiple doses (up to 160 mg BID) were evaluated in healthy volunteers in a randomized, double-blinded, placebo-controlled manner. ABT-639 demonstrated acceptable safety and pharmacokinetic profiles in human. Results from assessment of the routine laboratory variables showed an unexpected statistically significant and clinically relevant decrease in blood uric acid with the increase in ABT-639 dose, which is possibly due to inhibition in URAT1 transporter. Pharmacokinetic/pharmacodynamic models were constructed to characterize the relationship between ABT-639 exposure and uric acid response. The final model was a mechanism-based indirect response pharmacodynamic model with the stimulation of uric acid elimination by ABT-639. The model estimated K in values in males and females were 10.2 and 7.13 μmol/h, respectively. The model estimated K out was 0.033 1/h. ABT-639 concentration that can produce 50% stimulation in uric acid elimination was estimated to be 8,070 ng/mL. Based on the final model, further simulations were conducted to predict the effect of ABT-639 on uric acid in gout patients. The simulation results indicated that, if the urate-lowering response to ABT-639 in gout patients is similar to that in healthy subjects, ABT-639 BID doses of 140 mg or higher would be expected to provide clinically meaningful lowering of blood uric acid levels below the 380 μmol/L solubility limit of monosodium urate.

Racial disparities in the risk of Stevens-Johnson Syndrome and toxic epidermal necrolysis as urate-lowering drug adverse events in the United States.

PubMed

Lu, Na; Rai, Sharan K; Terkeltaub, Robert; Kim, Seoyoung C; Menendez, Mariano E; Choi, Hyon K

2016-10-01

HLA-B*5801 allele carriage (a strong determinant of allopurinol hypersensitivity syndrome) varies substantially among races, which may lead to racial disparities in the risk of Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) in the context of urate-lowering drug adverse events (ULDAEs). We examined this hypothesis in a large, racially diverse, and generalizable setting. Using a database representative of US hospitalizations (2009-2013), we investigated the racial distribution of hospitalized SJS/TEN (principal discharge diagnosis) as ULDAEs (ICD-9-CM Classification of External Causes). Our reference groups included the US Census population, US allopurinol users, and ULDAE hospitalizations without SJS/TEN. We identified 606 cases hospitalized for SJS/TEN as ULDAEs (mean age = 68 years; 44% male), among which there was an overrepresentation of Asians (27%) and Blacks (26%), and an underrepresentation of Whites (29%) and Hispanics (% too-low-to-report), compared with the US Census population (5%, 12%, 67%, and 15%, respectively). The hospitalization rate ratios for SJS/TEN among Asians, Blacks, and Whites were 11.9, 5.0, and 1.0 (referent), respectively. These associations persisted using other national referents. According to the NHANES 2009-2012, allopurinol constituted 96.8% of urate-lowering drug use, followed by probenecid (2.1%). These national data indicate that Asians and Blacks have a substantially higher risk of SJS/TEN as ULDAEs than Whites (or Hispanics), correlating well with corresponding frequencies of HLA-B*5801 in the US population (i.e., 7.4%, 4%, 1%, and 1%, respectively). Given its market dominance and established association with SJS/TEN, our findings support the use of vigilance in these minorities when considering allopurinol. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetic variation underlying renal uric acid excretion in Hispanic children: the Viva La Familia Study.

PubMed

Chittoor, Geetha; Haack, Karin; Mehta, Nitesh R; Laston, Sandra; Cole, Shelley A; Comuzzie, Anthony G; Butte, Nancy F; Voruganti, V Saroja

2017-01-17

Reduced renal excretion of uric acid plays a significant role in the development of hyperuricemia and gout in adults. Hyperuricemia has been associated with chronic kidney disease and cardiovascular disease in children and adults. There are limited genome-wide association studies associating genetic polymorphisms with renal urate excretion measures. Therefore, we investigated the genetic factors that influence the excretion of uric acid and related indices in 768 Hispanic children of the Viva La Familia Study. We performed a genome-wide association analysis for 24-h urinary excretion measures such as urinary uric acid/urinary creatinine ratio, uric acid clearance, fractional excretion of uric acid, and glomerular load of uric acid in SOLAR, while accounting for non-independence among family members. All renal urate excretion measures were significantly heritable (p <2 × 10 -6 ) and ranged from 0.41 to 0.74. Empirical threshold for genome-wide significance was set at p <1 × 10 -7 . We observed a strong association (p < 8 × 10 -8 ) of uric acid clearance with a single nucleotide polymorphism (SNP) in zinc finger protein 446 (ZNF446) (rs2033711 (A/G), MAF: 0.30). The minor allele (G) was associated with increased uric acid clearance. Also, we found suggestive associations of uric acid clearance with SNPs in ZNF324, ZNF584, and ZNF132 (in a 72 kb region of 19q13; p <1 × 10 -6 , MAFs: 0.28-0.31). For the first time, we showed the importance of 19q13 region in the regulation of renal urate excretion in Hispanic children. Our findings indicate differences in inherent genetic architecture and shared environmental risk factors between our cohort and other pediatric and adult populations.

The systems biology of uric acid transporters: the role of remote sensing and signaling.

PubMed

Nigam, Sanjay K; Bhatnagar, Vibha

2018-07-01

Uric acid homeostasis in the body is mediated by a number of SLC and ABC transporters in the kidney and intestine, including several multispecific 'drug' transporters (e.g., OAT1, OAT3, and ABCG2). Optimization of uric acid levels can be viewed as a 'systems biology' problem. Here, we consider uric acid transporters from a systems physiology perspective using the framework of the 'Remote Sensing and Signaling Hypothesis.' This hypothesis explains how SLC and ABC 'drug' and other transporters mediate interorgan and interorganismal communication (e.g., gut microbiome and host) via small molecules (e.g., metabolites, antioxidants signaling molecules) through transporters expressed in tissues lining body fluid compartments (e.g., blood, urine, cerebrospinal fluid). The list of uric acid transporters includes: SLC2A9, ABCG2, URAT1 (SLC22A12), OAT1 (SLC22A6), OAT3 (SLC22A8), OAT4 (SLC22A11), OAT10 (SLC22A13), NPT1 (SLC17A1), NPT4 (SLC17A3), MRP2 (ABCC2), MRP4 (ABCC4). Normally, SLC2A9, - along with URAT1, OAT1 and OAT3, - appear to be the main transporters regulating renal urate handling, while ABCG2 appears to regulate intestinal transport. In chronic kidney disease (CKD), intestinal ABCG2 becomes much more important, suggesting remote organ communication between the injured kidney and the intestine. The remote sensing and signaling hypothesis provides a useful systems-level framework for understanding the complex interplay of uric acid transporters expressed in different tissues involved in optimizing uric acid levels under normal and diseased (e.g., CKD, gut microflora dysbiosis) conditions.

Computed phase diagrams for the system: Sodium hydroxide-uric acid-hydrochloric acid-water

NASA Astrophysics Data System (ADS)

Brown, W. E.; Gregory, T. M.; Füredi-Milhofer, H.

1987-07-01

Renal stone formation is made complex by the variety of solid phases that are formed, by the number of components in the aqueous phase, and by the multiplicity of ionic dissociation and association processes that are involved. In the present work we apply phase diagrams calculated by the use of equilibrium constants from the ternary system sodium hydroxide-uric acid-water to simplify and make more rigorous the understanding of the factors governing dissolution and precipitation of uric acid (anhydrous and dihydrate) and sodium urate monohydrate. The system is then examined in terms of four components. Finally, procedures are described for fluids containing more than four components. The isotherms, singular points, and fields of supersaturation and undersaturation are shown in various forms of phase diagrams. This system has two notable features: (1) in the coordinates -log[H 2U] versus -log[NaOH], the solubility isotherms for anhydrous uric acid and uric acid dihydrate approximate straight lines with slopes equal to +1 over a wide range of concentrations. As a result, substantial quantities of sodium acid urate monohydrate can precipitate from solution or dissolve without changing the degree of saturation of uric acid significantly. (2) The solubility isotherm for NaHU·H 2O has a deltoid shape with the low-pH branch having a slope of infinity. As a result of the vertical slope of this isotherm, substantial quantities of uric acid can dissolve or precipitate without changing the degree of saturation of sodium acid urate monohydrate significantly. The H 2U-NaOH singular point has a pH of 6.87 at 310 K in the ternary system.

The Effect of Lesinurad in Combination With Allopurinol on Serum Uric Acid Levels in Patients With Gout.

PubMed

Baumgartner, Scott; Yeh, Li-Tain; Shen, Zancong; Kerr, Bradley; Manhard, Kimberly; Quart, Barry

2018-05-07

The objective of the study was to evaluate the effect of lesinurad, a selective uric acid uptake inhibitor, alone and in combination with the xanthine oxidase inhibitor allopurinol, on serum uric acid and urinary urate excretion in patients with gout and hyperuricemia. A phase 1b, multicenter, open-label, multiple-dose study was carried out in patients with gout with serum uric acid ≥8 mg/dL following washout of urate-lowering therapy. Patients were treated with allopurinol 300 mg/day alone in week 1; lesinurad 400 or 600 mg/day was added in week 2, followed by lesinurad 400 or 600 mg/day alone in week 3. Serum uric acid and urine uric acid were evaluated each week. Safety was assessed throughout the study. Lesinurad 400 or 600 mg/day added to allopurinol 300 mg/day reduced serum uric acid by 60% and 72%, respectively, versus allopurinol alone (37%) or lesinurad 400 mg/day (44%) or 600 mg/day (47%) alone. A 100% response rate of serum uric acid <6 mg/dL was achieved by all combinations (serum uric acid <5 mg/dL by 50%-90%). Mean 24-hour urate excretion compared with baseline was -35% with allopurinol, +36% and +56.5% with lesinurad 400 mg/day and 600 mg/day, respectively, and -11.6% and -7.1% with the respective combination therapies. Treatments were well tolerated. In this phase 1 trial, lesinurad added to allopurinol resulted in greater serum uric acid reduction than did allopurinol or lesinurad monotherapy. © 2018, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Imaging tools to measure treatment response in gout.

PubMed

Dalbeth, Nicola; Doyle, Anthony J

2018-01-01

Imaging tests are in clinical use for diagnosis, assessment of disease severity and as a marker of treatment response in people with gout. Various imaging tests have differing properties for assessing the three key disease domains in gout: urate deposition (including tophus burden), joint inflammation and structural joint damage. Dual-energy CT allows measurement of urate deposition and bone damage, and ultrasonography allows assessment of all three domains. Scoring systems have been described that allow radiological quantification of disease severity and these scoring systems may play a role in assessing the response to treatment in gout. This article reviews the properties of imaging tests, describes the available scoring systems for quantification of disease severity and discusses the challenges and controversies regarding the use of imaging tools to measure treatment response in gout. © The Author 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Histochemistry and ultrastructure of urocytes in the pupae of the stingless bee Melipona quadrifasciata (Hymenoptera: Meliponini).

PubMed

Furtado, Waléria C A; Azevedo, Dihego O; Martins, Gustavo F; Zanuncio, José C; Serrão, José Eduardo

2013-12-01

The main cell types of the adult bee fat body are trophocytes and oenocytes; however, in pupae of some newly emerged bees, trophocytes are modified into cells called urocytes, which possibly function as a substitute for Malpighian tubules during metamorphosis when larval tubules are not functional and/or storage of urate salts is required. This study evaluated the morphology of urocytes in the stingless bee Melipona quadrifasciata and the possibility of maintaining these cells in primary culture. The urocytes M. quadrifasciata are white spherical cells with an irregular surface as observed by stereomicroscopy. They may be found individually or in groups associated with tracheae. Urocytes have a single, small, and spherical nucleus and cytoplasm rich in neutral polysaccharides, lipid droplets, protein, and granules containing calcium and urate salts. Our findings suggest that urocytes play a role in storage of neutral polysaccharides and calcium in M. quadrifasciata pupae and that these cells can be cultured for 72 h.

Structure-Function Perturbation and Dissociation of Tetrameric Urate Oxidase by High Hydrostatic Pressure

PubMed Central

Girard, Eric; Marchal, Stéphane; Perez, Javier; Finet, Stéphanie; Kahn, Richard; Fourme, Roger; Marassio, Guillaume; Dhaussy, Anne-Claire; Prangé, Thierry; Giffard, Marion; Dulin, Fabienne; Bonneté, Françoise; Lange, Reinhard; Abraini, Jacques H.; Mezouar, Mohamed; Colloc'h, Nathalie

2010-01-01

Abstract Structure-function relationships in the tetrameric enzyme urate oxidase were investigated using pressure perturbation. As the active sites are located at the interfaces between monomers, enzyme activity is directly related to the integrity of the tetramer. The effect of hydrostatic pressure on the enzyme was investigated by x-ray crystallography, small-angle x-ray scattering, and fluorescence spectroscopy. Enzymatic activity was also measured under pressure and after decompression. A global model, consistent with all measurements, discloses structural and functional details of the pressure-induced dissociation of the tetramer. Before dissociating, the pressurized protein adopts a conformational substate characterized by an expansion of its substrate binding pocket at the expense of a large neighboring hydrophobic cavity. This substate should be adopted by the enzyme during its catalytic mechanism, where the active site has to accommodate larger intermediates and product. The approach, combining several high-pressure techniques, offers a new (to our knowledge) means of exploring structural and functional properties of transient states relevant to protein mechanisms. PMID:20483346

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peden, D.B.; Swiersz, M.; Ohkubo, K.

Uric acid, an important scavenger of ozone, has been identified as the major low molecular weight antioxidant in baseline and cholinergically induced nasal secretions. The purpose of this study was to determine the specific tissue source of uric acid in airway secretions. The secretion of uric acid is increased by cholinergic stimulation and correlates closely with the secretion of lactoferrin (a nasal glandular protein), suggesting that submucosal glands are involved. Indeed, nasal turbinate tissue was found to contain uric acid. However, careful analysis of nasal turbinate tissue failed to reveal the presence of xanthine oxidase, the enzyme responsible for uricmore » acid synthesis. These data suggest that uric acid might be taken up secondarily by glands from plasma. This possibility was strengthened by the observation that lowering the plasma urate level with probenecid concomitantly lowered urate secretion. These findings are consistent with the hypotheses that the principal source of uric acid in nasal secretions is plasma and that uric acid is taken up, concentrated, and secreted by nasal glands.« less

The Many Sides of Academic Dishonesty Sanctions

ERIC Educational Resources Information Center

Beasley, Eric Matthew

2012-01-01

In the fall of 2009, Michigan State University (MSU) implemented a new policy regarding reports of undergraduate academic dishonesty. Under the new system, instructors are required to submit an academic dishonesty report for any student that they penalize for violations of academic integrity, and these students are placed into a remediation class…

Supporting College Students through Peer Mentoring: Serving Immigrant Students

ERIC Educational Resources Information Center

Kring, Matthew

2017-01-01

Metropolitan State University of Denver (MSU Denver) Immigrant Services program enlists the support of peer mentors to provide holistic support to the institution's immigrant, refugee, and English Language Learner (ELL) populations. These peer mentors are highly specialized in their student employee role and are trained to provide academic and…

Rare Isotope Beams for the 21st Century

ScienceCinema

James Symons

2017-12-09

In a scientific keynote address on Friday, June 12 at Michigan State University (MSU) in East Lansing, James Symons, Director of Berkeley Labs Nuclear Science Division (NSD), discussed the exciting research prospects of the new Facility for Rare Isotope Beams (FRIB) to be built at MSUs National Superconducting Cyclotron Laboratory.

Instructional Support Costs Related to Faculty Salary Costs. Report No. 79-02.

ERIC Educational Resources Information Center

Hample, Stephen R.

Nonfaculty salary (instructional support) costs for Montana State University (MSU) are examined with specific reference to the adequacy of the 25 percent nonfaculty salary allowance for other costs. Two concepts are examined: nonfaculty salary expenses within the instruction program (direct instructional support costs) and both direct support…

Language Teachers' Target Language Project: Language for Specific Purposes of Language Teaching

ERIC Educational Resources Information Center

Korenev, Alexey; Westbrook, Carolyn; Merry, Yvonne; Ershova, Tatiana

2016-01-01

The Language Teachers' Target Language project (LTTL) aims to describe language teachers' target language use domain (Bachman & Palmer 2010) and to develop a language test for future teachers of English. The team comprises four researchers from Moscow State University (MSU) and Southampton Solent University.

The Strategies To Advance the Internationalization of Learning (SAIL) Program.

ERIC Educational Resources Information Center

Ebert, Kenneth B.; Burnett, Jane

This report documents the Strategies to Advance the Internalization of Learning (SAIL) program developed at Michigan State University (MSU) to promote international, comparative, and cross-cultural learning and cross-cultural understanding in the university community. A total of 350 foreign and U.S. students who had international experience…

Setting Evidence-Based Language Goals

ERIC Educational Resources Information Center

Goertler, Senta; Kraemer, Angelika; Schenker, Theresa

2016-01-01

The purpose of this project was to identify target language benchmarks for the German program at Michigan State University (MSU) based on national and international guidelines and previous research, to assess language skills across course levels and class sections in the entire German program, and to adjust the language benchmarks as needed based…

A Successful Retention Program for Suspended Students

ERIC Educational Resources Information Center

Dill, Anna L.; Gilbert, Jerome A.; Hill, Jennifer P.; Minchew, Sue S.; Sempier, Tracie A.

2011-01-01

Traditionally at Mississippi State University (MSU), students who are placed on academic suspension are required to stay out of school one regular semester. As an alternative, the university designed a program for early readmission for suspended students who agree to follow the requirements outlined in the "Learning Skills Support…

An International Short Course for Training Professionals as Effective Science Communicators

ERIC Educational Resources Information Center

Sarathchandra, Dilshani; Maredia, Karim M.

2014-01-01

Scholars have recognized a need for educational programs that prepare scientists, Extension practitioners, and other stakeholders to communicate science effectively. Such programs have the potential to increase public awareness and aid policy development. Having recognized this need, faculty at Michigan State University (MSU) developed an…

The Development of Beginning Mathematics Teacher Pedagogical Content Knowledge

ERIC Educational Resources Information Center

Lannin, John K.; Webb, Matthew; Chval, Kathryn; Arbaugh, Fran; Hicks, Sarah; Taylor, Cynthia; Bruton, Rebecca

2013-01-01

Recent research efforts (Schmidt et al. in "The preparation gap: teacher education for middle school mathematics in six countries," MSU Center for Research in Mathematics and Science Education, 2007) demonstrate that teacher development programs in high-performing countries offer experiences that are designed to develop both mathematical…

Seasonal variations in urinary risk factors among patients with nephrolithiasis

NASA Technical Reports Server (NTRS)

Hill, K.; Poindexter, J.; Pak, C. Y.

1991-01-01

Twenty-four hour urine specimens from 5,677 stone-forming patients throughout the United States were analyzed for seasonal variations in urinary risk factors for nephrolithiasis. Determinations were performed for urine volume, pH, calcium, oxalate, phosphorus, sodium, magnesium, citrate, sulfate, uric acid, and the relative supersaturation (RS) of calcium oxalate, brushite, monosodium urate, and uric acid. Criteria for significant seasonal variation included a significant difference in monthly means of risk factors, seasonal grouping of the data by the Student-Newman-Keuls multiple range test, consistent year-to-year trends and a physiologically significant range. Minimum urine volume of 1.54 +/- 0.70 SD L/day occurred in October while a maximum urine volume of 1.76 +/- 0.78 SD L/day was observed during February. Minimum urine pH of 5.94 +/- 0.64 SD was observed during July and August while a maximum pH of 6.18 +/- 0.61 SD was observed during February. Daily urinary excretion of sodium was lowest during August, 158 +/- 74 SD mEq/day and highest during February 177 +/- 70 SD mEq/day. The RS of brushite and uric acid were found to display significant pH-dependent seasonal variation with a maximum RS of uric acid 2.26 +/- 1.98 SD in June and a low of 1.48 +/- 1.30 SD in February. Maximum RS of brushite 2.75 +/- 2.58 was observed during February. Minimum RS of brushite 1.93 +/- 1.70 SD was observed in June. Phosphorus excretion displayed seasonal variation about a spring-fall axis with a maximum value 1042 +/- 373 SD mg/day in April and a minimum value of 895 +/- 289 SD mg/day. Urine volume, sodium, and pH were significantly lower during the summer (June, July, August) than in the winter (December, January, February). The RS of uric acid was higher, but that of brushite and monosodium urate was lower in the summer than in the winter. The seasonal changes observed in urine volume, pH, sodium, and the RS of brushite and uric acid are consistent with summertime sweating and increased physical activity. Seasonal variations in phosphorus excretion are probably dietary in origin. The summertime was characterized by an increased propensity for the crystallization of uric acid but not of calcium oxalate or calcium phosphate.

Academic Success of Suspended Students. AIR 2001 Annual Forum Paper.

ERIC Educational Resources Information Center

Howard, Richard D.; Borland, Ken; Johnson, Cel; Baker, Larry J.

Cohorts of entering freshmen were tracked over time to determine whether the suspension policy at Montana State University (MSU), Bozeman was having the intended effect on academic success, defined as degree completion. The university's current policy requires students to be suspended after receiving grade point averages (GPAs) of lower than 2.00…

Research in Second Language Studies at Michigan State University

ERIC Educational Resources Information Center

White, Benjamin; , Fei, Fei; Russell, Marthe

2009-01-01

The Second Language Studies (SLS) Program was established in 2005 with the express purpose of providing "a firm foundation in the field of Second Language Acquisition and its application to current second language research and teaching" (http://sls.msu.edu). Under the leadership of Professor Susan Gass, the program has grown to include…

Emerald ash borer in North America: a research and regulatory challenge

Treesearch

David Cappaert; Deborah G. McCullough; Therese M. Poland; Nathan W. Siegert

2005-01-01

The saga of the emerald ash borer, Agrilus planipennis Fairmare (Coleoptera: Buprestidae), in North America began on 25 June 2002, when five entomologists representing Michigan State University (MSU), the Michigan Department of Natural Resources (MDNR), and the U.S. Department of Agriculture, Animal and Plant Health Inspection Service (USDA APHIS)...

Land-Grant Extension as a Global Endeavor: Connecting Knowledge and International Development

ERIC Educational Resources Information Center

Collins, Christopher S.

2012-01-01

Two land-grant institutions, Michigan State University (MSU) and Texas A&M University (TAMU) used funding from the United States Agency for International Development (USAID) to partner with the National University of Rwanda (NUR) to support the agriculture faculty in Rwanda following the 1994 genocide. In addition, the three institutions…

Improving Instruction at MSU. J.W. Brister Library Monograph Series 7.

ERIC Educational Resources Information Center

Mayo, G. Douglas, Ed.

A program providing small grants to faculty members to carry out promising proposals for instructional improvement was undertaken at Memphis State University in 1974. Herein are included fifteen reports describing projects conducted during the third year of the program, and a report evaluating the small grant program. The reports focus on:…

Mental Models Research to Inform Community Outreach for a Campus Recycling Program

ERIC Educational Resources Information Center

Olson, Lauren; Arvai, Joseph; Thorp, Laurie

2011-01-01

Purpose: The purpose of this paper is to develop a better understanding of the state of knowledge of students and faculty on the Michigan State University (MSU) campus; identify relevant gaps in knowledge and misconceptions about recycling; and provide recommendations regarding how these gaps and misconceptions may be addressed through education…

MSU Libraries Student Employee Handbook.

ERIC Educational Resources Information Center

Delgado, LaDonne; Breland, June, Ed.; Turner, Susanna, Ed.

This manual was designed to give student employees of the Mitchell Memorial Library at Mississippi State University an understanding of what to expect from faculty and staff, and what is expected of all student employees of the Library. In general, the manual is aimed at helping student employees: develop a philosophy of service and promote a…

FRIB Cryogenic Distribution System and Status

NASA Astrophysics Data System (ADS)

Ganni, V.; Dixon, K.; Laverdure, N.; Yang, S.; Nellis, T.; Jones, S.; Casagrande, F.

2015-12-01

The MSU-FRIB cryogenic distribution system supports the 2 K primary, 4 K primary, and 35 - 55 K shield operation of more than 70 loads in the accelerator and the experimental areas. It is based on JLab and SNS experience with bayonet-type disconnects between the loads and the distribution system for phased commissioning and maintenance. The linac transfer line, which features three separate transfer line segments for additional independence during phased commissioning at 4 K and 2 K, connects the folded arrangement of 49 cryomodules and 4 superconducting dipole magnets and a fourth transfer line supports the separator area cryo loads. The pressure reliefs for the transfer line process lines, located in the refrigeration room outside the tunnel/accelerator area, are piped to be vented outdoors. The transfer line designs integrate supply and return flow paths into a combined vacuum space. The main linac distribution segments are produced in a small number of standard configurations; a prototype of one such configuration has been fabricated at Jefferson Lab and has been installed at MSU to support testing of a prototype FRIB cryomodule.

The Advanced Technology Microwave Sounder (ATMS): The First 10 Months On-Orbit

NASA Technical Reports Server (NTRS)

Kim, Edward; Lyu, C-H Joseph; Blackwell, Willaim; Leslie, R. Vince; Baker, Neal; Mo, Tsan; Sun, Ninghai; Bi, Li; Anderson, Kent; Landrum, Mike;

Mobile surveillance units (MSU) for border protection of the enlarged economic union

NASA Astrophysics Data System (ADS)

Crandon, Christopher

2004-12-01

During the last 12 years the European Union (EU) has financed the new member applicant countries of Central and Eastern Europe in their preparation for joining the EU. Based on this enlargement of the EU, funding for Cross Border Protection has been made available from the overall infrastructure improvement budget. Border protection was required in areas where border conflicts had taken place and to limit Illegal Immigration (II) and smuggling. After 9/11/2001, defence against terrorist activities will no doubt be added to the requirement. This paper describes the approach taken in the design of the latest "containerised" police and para military Mobile Surveillance Units (MSUs). This approach may also be considered for Homeland Security initiatives. These MSU's utilise standard road vehicles, and off-road variants, converted to use high performance military thermal imagers, such as SiGMA. In future the current, in service, MSUs will require increased sensor integration and networking to cover land and coastal borders. The underlying key is affordability for the police and para-military markets whilst retaining the highest performance derived from the latest SFPA military standard thermal imagers.

An updated version of NPIDB includes new classifications of DNA–protein complexes and their families

PubMed Central

Zanegina, Olga; Kirsanov, Dmitriy; Baulin, Eugene; Karyagina, Anna; Alexeevski, Andrei; Spirin, Sergey

2016-01-01

The recent upgrade of nucleic acid–protein interaction database (NPIDB, http://npidb.belozersky.msu.ru/) includes a newly elaborated classification of complexes of protein domains with double-stranded DNA and a classification of families of related complexes. Our classifications are based on contacting structural elements of both DNA: the major groove, the minor groove and the backbone; and protein: helices, beta-strands and unstructured segments. We took into account both hydrogen bonds and hydrophobic interaction. The analyzed material contains 1942 structures of protein domains from 748 PDB entries. We have identified 97 interaction modes of individual protein domain–DNA complexes and 17 DNA–protein interaction classes of protein domain families. We analyzed the sources of diversity of DNA–protein interaction modes in different complexes of one protein domain family. The observed interaction mode is sometimes influenced by artifacts of crystallization or diversity in secondary structure assignment. The interaction classes of domain families are more stable and thus possess more biological sense than a classification of single complexes. Integration of the classification into NPIDB allows the user to browse the database according to the interacting structural elements of DNA and protein molecules. For each family, we present average DNA shape parameters in contact zones with domains of the family. PMID:26656949

Should the presence of a culture positive urinary tract infection exclude patients from rapid evaluation hematuria protocols?

PubMed

Vasdev, Nikhil; Thorpe, Andrew C

2013-08-01

Current rapid evaluation protocols for patients with hematuria tend to exclude those with urinary tract infection since this is assumed to be evidence of a benign treatable cause. The likelihood of a urinary tract cancer in such patients is, however, uncertain, and we have therefore analyzed a prospective hematuria clinic database to determine risk. A total of 1,740 patients were enrolled prospectively in this study at our unit's one stop fast track hematuria clinic between April 2003 and March 2006. Evaluation of patients consisted of basic demographics, history and examination, urinalysis, urine culture, urine cytology, and serum creatinine. All patients then underwent a renal ultrasound, intravenous urogram, and cystoscopy. A total of 1,067 males and 673 females with a mean (range) age of 60.8 (16-96) years were included in the study. One hundred sixty-one patients had a positive mid-stream urine (MSU) on a specimen collected at the hematuria clinic. Amongst this group 20% (32) patients had a urologic malignancy diagnosed, of whom 12% (4) had metastatic disease at presentation. Only 1% (3) of patients had a urologic malignancy with a previous history of a treated urinary tract infection (UTI) and negative MSU at the clinic. The risk of urologic malignancy was 24% (303) in the remaining 1,249 patients with no history of a UTI prior to presentation and a negative MSU on a specimen collected at the one stop fast track hematuria clinic. Despite selection bias inherent in this analysis, it appears that the presence of UTI does not decrease the likelihood of having a urologic malignancy diagnosed. Hence, there is no indication to delay prompt evaluation in patients with hematuria and a positive urine culture collected at the hematuria clinic. Copyright © 2013 Elsevier Inc. All rights reserved.

Validating a large geophysical data set: Experiences with satellite-derived cloud parameters

NASA Technical Reports Server (NTRS)

Kahn, Ralph; Haskins, Robert D.; Knighton, James E.; Pursch, Andrew; Granger-Gallegos, Stephanie

1992-01-01

We are validating the global cloud parameters derived from the satellite-borne HIRS2 and MSU atmospheric sounding instrument measurements, and are using the analysis of these data as one prototype for studying large geophysical data sets in general. The HIRS2/MSU data set contains a total of 40 physical parameters, filling 25 MB/day; raw HIRS2/MSU data are available for a period exceeding 10 years. Validation involves developing a quantitative sense for the physical meaning of the derived parameters over the range of environmental conditions sampled. This is accomplished by comparing the spatial and temporal distributions of the derived quantities with similar measurements made using other techniques, and with model results. The data handling needed for this work is possible only with the help of a suite of interactive graphical and numerical analysis tools. Level 3 (gridded) data is the common form in which large data sets of this type are distributed for scientific analysis. We find that Level 3 data is inadequate for the data comparisons required for validation. Level 2 data (individual measurements in geophysical units) is needed. A sampling problem arises when individual measurements, which are not uniformly distributed in space or time, are used for the comparisons. Standard 'interpolation' methods involve fitting the measurements for each data set to surfaces, which are then compared. We are experimenting with formal criteria for selecting geographical regions, based upon the spatial frequency and variability of measurements, that allow us to quantify the uncertainty due to sampling. As part of this project, we are also dealing with ways to keep track of constraints placed on the output by assumptions made in the computer code. The need to work with Level 2 data introduces a number of other data handling issues, such as accessing data files across machine types, meeting large data storage requirements, accessing other validated data sets, processing speed and throughput for interactive graphical work, and problems relating to graphical interfaces.

Nanobiology for the pharmacology of cellular ion channels.

PubMed

Kabanov, Alexander V; Kirpichnikov, Mikhail P; Khokhlov, Alexey R

2009-03-01

Writing this editorial is especially pleasing. First, it provides us an opportunity to introduce new directives to the field of Neuroimmune Pharmacology and to explain why the field of nanomedicine is likely an important part of its future growth and development. Second, it is an opportunity to showcase research in this area currently operative in Russia that may not be readily accessible to the readership. Third, it is a platform to better explain why the Journal Editorial leadership was enthusiastic about the science and its relationship to the Society on NeuroImmune Pharmacology strategic goals. All are brought to bear in this issue of the Journal of Neuroimmune Pharmacology. The issue includes articles presented at a recent joint US-Russian workshop entitled, "Health in the 21st Century: Nanomedicine and Self-Organization of Biological Systems" held at M.V. Lomonosov Moscow State University (MSU), Moscow, Russia, December 10-11, 2007. The conjoint meeting was organized through the Departments of Biology, Chemistry, and Physics, MSU and by the Center for Drug Delivery and Nanomedicine and Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center (Omaha, NE). The speakers included established internationally regarded scientists from these institutions as well as graduate students and faculties at MSU. In addition to selected papers by workshop contributors, we have included several papers closely aligned to the theme of nanomedicine and nanopharmacology of the central nervous system in order to provide a biological anchor for this research. We understand that such works are new to many but hope that its organization and interdisciplinary approaches will appeal to this audience. All together, it is our hope that, by gathering basic and clinical scientists with the common interest of using nanotechnology in the delivery of therapeutic agents with a focus on nanopharmacology and complex supramolecular biological assembly, the papers included will provide a platform for thought, discussion, and future translational research.

Integrating animal welfare into veterinary education: using an online, interactive course.

PubMed

Siegford, Janice M; Bernardo, Theresa M; Malinowski, Robert P; Laughlin, Kirsty; Zanella, Adroaldo J

2005-01-01

Veterinarians in the United States and abroad are faced with growing public concern for the welfare of animals, particularly those in production. To prepare veterinarians to exert the leadership expected by the public and industry, steps should be taken to provide instruction in animal welfare at veterinary colleges. The ultimate goal is to offer courses in animal welfare in a consistent manner on a global scale, utilizing existing expertise in an efficient and cost-effective manner. Given the intense curricula of veterinary schools and the scarcity of instructors trained in animal welfare, a nontraditional approach is needed to educate veterinary students in the United States and abroad in animal welfare. Michigan State University (MSU) is developing a graduate-level, online interactive course in animal welfare assessment. The course will approach the topic of animal welfare education from a holistic, multidisciplinary standpoint (encompassing ethics, economics, and behavior) and address issues important to the general public and the international community. The MSU course will draw on renowned international animal welfare experts, allowing students to receive high-quality education that would be difficult in any other circumstance. The course will bridge an important gap in the veterinary curriculum and offer a complete and congruous education in animal welfare to veterinarians worldwide. The MSU course will also serve as a model for collaboration in content assembly and course delivery, by using technology to leverage global expertise in the interests of educational equity. In addition to innovative technology, such as the use of Web-collaboration software to create the course, a variety of media that enable students to interact with the material will also be incorporated throughout the course. Thus, the course will not only utilize the Internet to provide access to high-quality material, but will also require the active participation of the student, which is needed for effective learning.

A Demonstration of an Improved Filtering Technique for Analyzing Climate Records via Comparisons of Satellite MSU/AMSU Instrument Temperature Products from Three Research Groups

NASA Astrophysics Data System (ADS)

Swanson, R. E.

2017-12-01

Climate data records typically exhibit considerable variation over short time scales both from natural variability and from instrumentation issues. The use of linear least squares regression can provide overall trend information from noisy data, however assessing intermediate time periods can also provide useful information unavailable from basic trend calculations. Extracting the short term information in these data for assessing changes to climate or for comparison of data series from different sources requires the application of filters to separate short period variations from longer period trends. A common method used to smooth data is the moving average, which is a simple digital filter that can distort the resulting series due to the aliasing of the sampling period into the output series. We utilized Hamming filters to compare MSU/AMSU satellite time series developed by three research groups (UAH, RSS and NOAA STAR), the results published in January 2017 [http://journals.ametsoc.org/doi/abs/10.1175/JTECH-D-16-0121.1]. Since the last release date (July 2016) for the data analyzed in that paper, some of these groups have updated their analytical procedures and additional months of data are available to extend the series. An updated analysis of these data using the latest data releases available from each group is to be presented. Improved graphics will be employed to provide a clearer visualization of the differences between each group's results. As in the previous paper, the greatest difference between the UAH TMT series and those from the RSS and NOAA data appears during the early period of data from the MSU instruments before about 2003, as shown in the attached figure, and preliminary results indicate this pattern continues. Also to be presented are other findings regarding seasonal changes which were not included in the previous study.

Abnormal, Error-Prone Bypass of Photoproducts by Xeroderma Pigmentosum Variant Cell Extracts Results in Extreme Strand Bias for the Kinds of Mutations Induced by UV Light

PubMed Central

McGregor, W. Glenn; Wei, Dong; Maher, Veronica M.; McCormick, J. Justin

1999-01-01

Xeroderma pigmentosum (XP) is a rare genetic disease characterized by a greatly increased susceptibility to sunlight-induced skin cancer. Cells from the majority of patients are defective in nucleotide excision repair. However, cells from one set of patients, XP variants, exhibit normal repair but are abnormally slow in replicating DNA containing UV photoproducts. The frequency of UV radiation-induced mutations in the XP variant cells is significantly higher than that in normal human cells. Furthermore, the kinds of UV-induced mutations differ very significantly from normal. Instead of transitions, mainly C→T, 30% of the base substitutions consist of C→A transversions, all arising from photoproducts located in one strand. Mutations involving cytosine in the other strand are almost all C→T transitions. Forty-five percent of the substitutions involve thymine, and the majority are transversions. To test the hypothesis that the UV hypermutability and the abnormal spectrum of mutations result from abnormal bypass of photoproducts in DNA, we compared extracts from XP variant cells with those from HeLa cells and a fibroblast cell strain, MSU-1.2, for the ability to replicate a UV-irradiated form I M13 phage. The M13 template contains a simian virus 40 origin of replication located directly to the left or to the right of the target gene, lacZα, so that the template for the leading and lagging strands of DNA replication is defined. Reduction of replication to ∼37% of the control value required only 1 photoproduct per template for XP variant cell extracts, but ∼2.2 photoproducts for HeLa or MSU-1.2 cell extracts. The frequency of mutants induced was four times higher with XP variant cell extracts than with HeLa or MSU-1.2 cell extracts. With XP variant cell extracts, the proportion of C→A transversions reached as high as 43% with either M13 template and arose from photoproducts located in the template for leading-strand synthesis; with HeLa or MSU-1.2 cell extracts, this value was only 5%, and these arose from photoproducts in either strand. With the XP variant extracts, 26% of the substitutions involved thymine, and virtually all were T→A transversions. Sequence analysis of the coding region of the catalytic subunit of DNA polymerase delta in XP variant cell lines revealed two polymorphisms, but these do not account for the reduced bypass fidelity. Our data indicate that the UV hypermutability of XP variant cells results from reduced bypass fidelity and that unlike for normal cells, bypass of photoproducts involving cytosine in the template for the leading strand differs significantly from that of photoproducts in the lagging strand. PMID:9858539

The risk of renal stone formation during and after long duration space flight

NASA Technical Reports Server (NTRS)

Whitson, P. A.; Pietrzyk, R. A.; Morukov, B. V.; Sams, C. F.

2001-01-01

BACKGROUND: The formation of a renal stone during space flight may have serious negative effects on the health of the crewmember and the success of the mission. Urinary biochemical factors and the influence of dietary factors associated with renal stone development were assessed during long duration Mir Space Station missions. METHODS: Twenty-four-hour urine samples were collected prior to, during and following long duration space flight. The relative urinary supersaturation of calcium oxalate, calcium phosphate (brushite), sodium urate, struvite and uric acid were determined. RESULTS: Changes in the urinary biochemistry of crewmembers during long duration spaceflight demonstrated increases in the supersaturation of the stone-forming salts. In-flight hypercalciuria was evident in a number of individual crewmembers and 24-hour dietary fluid intake and urine volume were significantly lower. During flight, there was a significant increase in brushite supersaturation. CONCLUSIONS: These data suggest acute effects of space flight and postflight changes in the urinary biochemistry favoring increased crystallization in the urine. The effects of dietary intake, especially fluid intake, may have a significant impact on the potential for renal stone formation. Efforts are now underway to assess the efficacy of a countermeasure to mitigate the increased risk. Copyright 2001 S. Karger AG, Basel.

Generation of therapeutic protein variants with the human serum albumin binding capacity via site-specific fatty acid conjugation.

PubMed

Cho, Jinhwan; Lim, Sung In; Yang, Byung Seop; Hahn, Young S; Kwon, Inchan

2017-12-21

Extension of the serum half-life is an important issue in developing new therapeutic proteins and expanding applications of existing therapeutic proteins. Conjugation of fatty acid, a natural human serum albumin ligand, to a therapeutic protein/peptide was developed as a technique to extend the serum half-life in vivo by taking advantages of unusually long serum half-life of human serum albumin (HSA). However, for broad applications of fatty acid-conjugation, several issues should be addressed, including a poor solubility of fatty acid and a substantial loss in the therapeutic activity. Therefore, herein we systematically investigate the conditions and components in conjugation of fatty acid to a therapeutic protein resulting in the HSA binding capacity without compromising therapeutic activities. By examining the crystal structure and performing dye conjugation assay, two sites (W160 and D112) of urate oxidase (Uox), a model therapeutic protein, were selected as sites for fatty acid-conjugation. Combination of site-specific incorporation of a clickable p-azido-L-phenylalanine to Uox and strain-promoted azide-alkyne cycloaddition allowed the conjugation of fatty acid (palmitic acid analog) to Uox with the HSA binding capacity and retained enzyme activity. Deoxycholic acid, a strong detergent, greatly enhanced the conjugation yield likely due to the enhanced solubility of palmitic acid analog.

ABCG2 contributes to the development of gout and hyperuricemia in a genome-wide association study.

PubMed

Chen, Chung-Jen; Tseng, Chia-Chun; Yen, Jeng-Hsien; Chang, Jan-Gowth; Chou, Wen-Cheng; Chu, Hou-Wei; Chang, Shun-Jen; Liao, Wei-Ting

2018-02-16

Although many genome-wide association studies (GWASs) of hyperuricemia or gout have been reported, the related genetic factors and the mechanisms from hyperuricemia to gouty attack remain unclear. This study aimed to identify genetic factors and pathogenesis of gout from hyperuricemia by genome-wide association study (GWAS). 747 gout patients, 747 hyperuricemia and 2071 age-matched controls were recruited and analyzed with Affymetrix 650 K chip to find the related genetic variants. The functions of the related genes were investigated in an endothelial cell (EC) with urate crystal stimulation. The GWAS results showed 36 SNPs to be strongly associated with gout compared to controls (all p-values < 10 -7 ). Whereas the rs2231142 in ABCG2 gene had significant associations between gout and controls, between gout and hyperuricemia, and between hyperuricemia and controls (all p-values < 10 -7 ), and the ORs were 4.34, 3.37 and 2.15 (all p-values < 0.001) after adjustment of potential confounders, respectively. The cell model showed significantly higher IL-8 release from EC combined with ABCG2 knockdown. We concluded that ABCG2 gene contributed to hyperuricemia but also gout, and that it was involved in the inflammation dysregulation via augmented IL-8 release in EC.

Population pharmacokinetic analysis of blood and joint synovial fluid concentrations of robenacoxib from healthy dogs and dogs with osteoarthritis.

PubMed

Silber, Hanna E; Burgener, Claudia; Letellier, Ingrid M; Peyrou, Mathieu; Jung, Martin; King, Jonathan N; Gruet, Philippe; Giraudel, Jerome M

2010-12-01

The purpose of this population analysis was to characterize the pharmacokinetic properties of robenacoxib in blood and stifle joint synovial fluid of dogs. Data were obtained from two studies: 1) 8 healthy Beagle dogs in which an acute inflammation was induced by injection of urate crystals into one joint; 2) 95 dogs from various breeds diagnosed with osteoarthritis (OA). Robenacoxib concentrations in blood and synovial fluid were measured using a validated HPLC-UV and LC-MS method. Non-linear mixed effects modeling was performed using NONMEM6. A two-compartment pharmacokinetic model with linear elimination was developed to describe blood concentrations of robenacoxib. Blood clearance in healthy animals was found to be 75% higher than in OA dogs. Synovial fluid concentrations were modeled using an effect-compartment-type model predicting longer residence times in OA dogs compared to healthy Beagles (e.g. concentrations above the IC(50) for COX-2, respectively, 16 h vs. 10 h at 1.5 mg/kg). Robenacoxib was found to reside longer at the effect site (inflamed joint) compared to blood in both healthy and OA dogs. These results may explain the good efficacy observed with once-daily dosing in clinical trials and the high safety index of robenacoxib in dogs.

Concentrating Solar Power Projects - Urat 50MW Fresnel CSP project |

Science.gov Websites

Concentrating Solar Power | NREL 50MW Fresnel CSP project Status Date: September 29, 2016 Turbine Capacity: Net: 50.0 MW Gross: 50.0 MW Status: Under development Do you have more information , corrections, or comments? Background Technology: Linear Fresnel reflector Status: Under development Country

The pharmacokinetics of oxypurinol in people with gout

PubMed Central

Stocker, Sophie L; McLachlan, Andrew J; Savic, Radojka M; Kirkpatrick, Carl M; Graham, Garry G; Williams, Kenneth M; Day, Richard O

2012-01-01

AIMS Our aim was to identify and quantify the sources of variability in oxypurinol pharmacokinetics and explore relationships with plasma urate concentrations. METHODS Non-linear mixed effects modelling was applied to concentration–time data from 155 gouty patients with demographic, medical history and renal transporter genotype information. RESULTS A one compartment pharmacokinetic model with first order absorption best described the oxypurinol concentration–time data. Renal function and concomitant medicines (diuretics and probenecid), but not transporter genotype, significantly influenced oxypurinol pharmacokinetics and reduced the between subject variability in the apparent clearance of oxypurinol (CL/Fm) from 65% to 29%. CL/Fm for patients with normal, mild, moderate and severe renal impairment was 1.8, 0.6, 0.3 and 0.18 l h−1, respectively. Model predictions showed a relationship between plasma oxypurinol and urate concentrations and failure to reach target oxypurinol concentrations using suggested allopurinol dosing guidelines. CONCLUSIONS In conclusion, this first established pharmacokinetic model provides a tool to achieve target oxypurinol plasma concentrations, thereby optimizing the effectiveness and safety of allopurinol therapy in gouty patients with various degrees of renal impairment. PMID:22300439

The anti-hyperuricemic effect of epigallocatechin-3-gallate (EGCG) on hyperuricemic mice.

PubMed

Zhu, Chuang; Xu, Yan; Liu, Zeng-Hui; Wan, Xiao-Chun; Li, Da-Xiang; Tai, Ling-Ling

2018-01-01

Epigallocatechin-3-gallate (EGCG), a major constituent of green tea catechin, has been used for antioxidant. This study aimed to evaluate the antihyperuricemic activity of EGCG on hyperuricemic mice. We demonstrated that serum uric acid (UA) level was decreased significantly with dose-dependence by EGCG treated with 10, 20, and 50mg/kg. Compared with the model, data on blood urea nitrogen (BUN) supported that there was significance with high dose of EGCG (50mg/kg). Levels of serum creatinine (Cr) in each EGCG-treated group were decreased but not significant; the activities of hepatic xanthine oxidase (XOD) and adenosine deaminase (ADA) in high dose groups' EGCG were notably lower than those of model group. EGCG could downregulate the renal mRNA expression levels of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) on hyperuricemic mice. These results presented that EGCG had obvious hypouricemic and renal protective effects on hyperuricemic mice. Our data may have a potential value in clinical practice in the treatment of hyperuricemia. Copyright © 2017. Published by Elsevier Masson SAS.

Evaluation of Personal Response Systems from a Teaching Perspective

ERIC Educational Resources Information Center

Dailey, Rocky Allan

2012-01-01

The purpose of this qualitative transcendental phenomenological study was to examine the usage, attitudes, and perceptions of personal response system (PRS) use by teaching faculty who had used the technology in at least one course at Montana State University (MSU) in Bozeman in the past six years. Fifteen faculty members who had used PRS in their…

A Bibliography on Rural Development in Tanzania. MSU Rural Development Paper No. 3.

ERIC Educational Resources Information Center

Kocher, James E.; Fleisher, Beverly

Rural development is understood to mean both the increased productivity of agriculture and other rural economic activities and the enhancement of the material well-being of the rural people (who comprise about 90% of Tanzania's 16 million population) through education, improved health, and better nutrition. Seven hundred and sixty-one books,…

Theory Loves Practice: A Teacher Researcher Group

ERIC Educational Resources Information Center

Hochtritt, Lisa; Thulson, Anne; Delaney, Rachael; Dornbush, Talya; Shay, Sarah

2014-01-01

Once a month, art educators from the Denver metro area have been gathering together in the spirit of inquiry to explore issues of the perceived theory and daily practice divide. The Theory Loves Practice (TLP) group was started in 2010 by Professors Rachael Delaney and Anne Thulson from Metropolitan State University of Denver (MSU) and now has 40…

The MSU Educational Technology Certificate Courses and Their Impact on Teachers' Growth as Technology Integrators

ERIC Educational Resources Information Center

Hagerman, Michelle Schira; Keller, Alison; Spicer, Jodi L.

2013-01-01

The Educational Technology Certificate (ETC.) courses at Michigan State University are a set of three courses that can be taken as a standalone qualification or as the first three courses in the Master's of Educational Technology degree. Together, the courses emphasize the development of technology skills and advanced mindsets for technology…

Exploring Management Strategies to Reduce Cheating in Written Examinations: Case Study of Midlands State University

ERIC Educational Resources Information Center

Taderera, Ever; Nyikahadzoi, Loveness; Matamande, Wilson; Mandimika, Elinah

2014-01-01

This study was concerned about cheating in written examinations at Midlands State University (MSU). The study revealed that both male and female students cheat in written examination; business studies students cheat more than other faculties, and younger (lower class) students cheat more than (upper class) older students. Factors influencing…

What Motivates Biology Instructors to Engage and Persist in Teaching Professional Development?

ERIC Educational Resources Information Center

McCourt, Jill S.; Andrews, Tessa C.; Knight, Jennifer K.; Merrill, John E.; Nehm, Ross H.; Pelletreau, Karen N.; Prevost, Luanna B.; Smith, Michelle K.; Urban-Lurain, Mark; Lemons, Paula P.

2017-01-01

We conducted a study of 19 biology instructors participating in small, local groups at six research-intensive universities connected to the Automated Analysis of Constructed Response (AACR) project (www.msu.edu/~aacr). Our aim was to uncover participants' motivation to persist in a long-term teaching professional development effort, a topic that…

Streamlining Transportation Corridors Planning Processes and Validating the Application of Commercial Remote Sensing and Spatial Information (CRS-SI) Technologies for Environmental Impact Assessments

DOT National Transportation Integrated Search

2008-02-05

The new US DOT RITA program has selected MSU for addressing corridor planning and environmental assessment in new and innovative ways that can be compared to traditional approaches. Our primary focus is on the application and validation of new and in...

A Passion for Africa

ERIC Educational Resources Information Center

Oguntoyinbo, Lekan

2011-01-01

The malaria center is at the heart of the kind of work Michigan State University's (MSU) African Studies Center has been engaged in on the African continent since it was founded half a century ago. The university is marking the center's 50th anniversary this year with a series of events that include large photo exhibits at one of the university's…

Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes

PubMed Central

Matsuo, Hirotaka; Yamamoto, Ken; Nakaoka, Hirofumi; Nakayama, Akiyoshi; Sakiyama, Masayuki; Chiba, Toshinori; Takahashi, Atsushi; Nakamura, Takahiro; Nakashima, Hiroshi; Takada, Yuzo; Danjoh, Inaho; Shimizu, Seiko; Abe, Junko; Kawamura, Yusuke; Terashige, Sho; Ogata, Hiraku; Tatsukawa, Seishiro; Yin, Guang; Okada, Rieko; Morita, Emi; Naito, Mariko; Tokumasu, Atsumi; Onoue, Hiroyuki; Iwaya, Keiichi; Ito, Toshimitsu; Takada, Tappei; Inoue, Katsuhisa; Kato, Yukio; Nakamura, Yukio; Sakurai, Yutaka; Suzuki, Hiroshi; Kanai, Yoshikatsu; Hosoya, Tatsuo; Hamajima, Nobuyuki; Inoue, Ituro; Kubo, Michiaki; Ichida, Kimiyoshi; Ooyama, Hiroshi; Shimizu, Toru; Shinomiya, Nariyoshi

2016-01-01

Objective Gout, caused by hyperuricaemia, is a multifactorial disease. Although genome-wide association studies (GWASs) of gout have been reported, they included self-reported gout cases in which clinical information was insufficient. Therefore, the relationship between genetic variation and clinical subtypes of gout remains unclear. Here, we first performed a GWAS of clinically defined gout cases only. Methods A GWAS was conducted with 945 patients with clinically defined gout and 1213 controls in a Japanese male population, followed by replication study of 1048 clinically defined cases and 1334 controls. Results Five gout susceptibility loci were identified at the genome-wide significance level (p<5.0×10−8), which contained well-known urate transporter genes (ABCG2 and SLC2A9) and additional genes: rs1260326 (p=1.9×10−12; OR=1.36) of GCKR (a gene for glucose and lipid metabolism), rs2188380 (p=1.6×10−23; OR=1.75) of MYL2-CUX2 (genes associated with cholesterol and diabetes mellitus) and rs4073582 (p=6.4×10−9; OR=1.66) of CNIH-2 (a gene for regulation of glutamate signalling). The latter two are identified as novel gout loci. Furthermore, among the identified single-nucleotide polymorphisms (SNPs), we demonstrated that the SNPs of ABCG2 and SLC2A9 were differentially associated with types of gout and clinical parameters underlying specific subtypes (renal underexcretion type and renal overload type). The effect of the risk allele of each SNP on clinical parameters showed significant linear relationships with the ratio of the case–control ORs for two distinct types of gout (r=0.96 [p=4.8×10−4] for urate clearance and r=0.96 [p=5.0×10−4] for urinary urate excretion). Conclusions Our findings provide clues to better understand the pathogenesis of gout and will be useful for development of companion diagnostics. PMID:25646370

Influence of the ABCG2 gout risk 141 K allele on urate metabolism during a fructose challenge.

PubMed

Dalbeth, Nicola; House, Meaghan E; Gamble, Gregory D; Pool, Bregina; Horne, Anne; Purvis, Lauren; Stewart, Angela; Merriman, Marilyn; Cadzow, Murray; Phipps-Green, Amanda; Merriman, Tony R

2014-01-30

Both genetic variation in ATP-binding cassette sub-family G member 2 (ABCG2) and intake of fructose-containing beverages are major risk factors for hyperuricemia and gout. This study aimed to test the hypothesis that the ABCG2 gout risk allele 141 K promotes the hyperuricaemic response to fructose loading. Healthy volunteers (n = 74) provided serum and urine samples immediately before and 30, 60, 120 and 180 minutes after ingesting a 64 g fructose solution. Data were analyzed based on the presence or absence of the ABCG2 141 K gout risk allele. The 141 K risk allele was present in 23 participants (31%). Overall, serum urate (SU) concentrations during the fructose load were similar in those with and without the 141 K allele (PSNP = 0.15). However, the 141 K allele was associated with a smaller increase in SU following fructose intake (PSNP <0.0001). Those with the 141 K allele also had a smaller increase in serum glucose following the fructose load (PSNP = 0.002). Higher fractional excretion of uric acid (FEUA) at baseline and throughout the fructose load was observed in those with the 141 K risk allele (PSNP <0.0001). However, the change in FEUA in response to fructose was not different in those with and without the 141 K risk allele (PSNP = 0.39). The 141 K allele effects on serum urate and glucose were more pronounced in Polynesian participants and in those with a body mass index ≥25 kg/m². In contrast to the predicted responses for a hyperuricemia/gout risk allele, the 141 K allele is associated with smaller increases in SU and higher FEUA following a fructose load. The results suggest that ABCG2 interacts with extra-renal metabolic pathways in a complex manner to regulate SU and gout risk. The study was registered by the Australian Clinical Trials Registry (ACTRN12610001036000).

Urolithiasis in dogs. II: Breed prevalence, and interrelations of breed, sex, age, and mineral composition.

PubMed

Ling, G V; Franti, C E; Ruby, A L; Johnson, D L

1998-05-01

To analyze selected breed-related data for canine urinary calculi. 11,000 specimens: 5,781 from female dogs, 5,215 from males, and 4 from dogs of unrecorded sex. Information was compiled for all canine urinary calculi submitted between July 1981 and January 1994. Results for a mixed-breed group and 26 of the most common breeds of stone-forming dogs were analyzed. Interrelations of breed, sex, and age of affected dogs and mineral composition of the specimens were determined. Prevalence of 5 specific mineral types was significantly correlated between the sexes of 27 common breed groups: struvite, calcium phosphate (apatite), calcium oxalate, brushite, and urate. Struvite-containing calculi were seen in high proportions in both sexes of 7 breeds, and in low proportions in both sexes of 7 other breeds. Male and female Lhasa Apsos, Cairn Terriers, and 5 other breeds had high proportions of oxalate-containing calculi; values in males were substantially higher. Low numbers of oxalate-containing calculi were seen in both sexes of 7 breeds; Dalmatians had the lowest numbers. Males and females of 6 breeds had high numbers of urate-containing calculi, Dalmatians and English Bulldogs had the highest numbers. Low amounts of urate were found in calculi from males and females of 6 breeds, Samoyeds had the lowest numbers. Highest proportions of cystine-containing calculi were seen in male Dachshunds, English Bulldogs, and Chihuahuas. Males of 8 breeds had no specimens that contained cystine; only 2 such specimens were obtained from females. Prevalence of uroliths differs among breed, age, and sex of affected dogs. Breed, sex, and age of dogs; mineral types of calculi in males versus females; and their anatomic location within the tract are important considerations for clinicians when evaluating risk in dogs with urolithiasis and in identifying areas that need further in-depth applied or clinical investigation, or both.

Anemia and the onset of gout in a population-based cohort of adults: Atherosclerosis Risk in Communities study

PubMed Central

2012-01-01

Introduction There is a growing prevalence of gout in the US and worldwide. Gout is a recognized risk factor for cardiovascular disease (CVD). It is unclear whether other risk factors for CVD are also associated with increased risk of gout. Anemia is one such CVD risk factor. No studies have evaluated the relationship between anemia and gout. We tested whether anemia was associated with incident gout independent of comorbid conditions in Atherosclerosis Risk in the Communities. Methods This population-based cohort recruited 15,792 individuals in 1987 to 1989 from four US communities and contained nine years of follow-up. Anemia was defined as hemoglobin <13.5 g/dL for men and <12 g/dL for women. Using a Cox Proportional Hazards model, we estimated the hazard ratio (HR) and confidence intervals (CI) of incident gout by baseline anemia, adjusted for confounders (sex, race, estimated glomerular filtration rate, body mass index and alcohol intake) and clinical factors (coronary heart disease, congestive heart failure, diabetes, hypertension, diuretic use and serum urate level). Results Among the 10,791 participants, 10% had anemia at baseline. There were 271 cases of incident gout. Patients with anemia had a two-fold increased risk of developing gout over nine years (HR = 2.01, 95% CI: 1.46, 2.76). Anemia was associated with incident gout independent of known gout risk factors, confounders and clinical risk factors (HR = 1.73, 95% CI: 1.24, 2.41). This association persisted after additionally adjusting for serum urate level (HR = 1.83, 95% CI: 1.30, 2.57). Conclusion We identified anemia as a novel risk factor for gout. Anemia was associated with an approximately two-fold increased risk of gout-independent kidney function and serum urate. These findings suggest that anemia is a risk factor for gout on par with other chronic conditions such as obesity and diabetes. The biological mechanism linking anemia to gout remains unclear. PMID:22906142

Anemia and the onset of gout in a population-based cohort of adults: Atherosclerosis Risk in Communities study.

PubMed

McAdams-DeMarco, Mara A; Maynard, Janet W; Coresh, Josef; Baer, Alan N

2012-08-20

There is a growing prevalence of gout in the US and worldwide. Gout is a recognized risk factor for cardiovascular disease (CVD). It is unclear whether other risk factors for CVD are also associated with increased risk of gout. Anemia is one such CVD risk factor. No studies have evaluated the relationship between anemia and gout. We tested whether anemia was associated with incident gout independent of comorbid conditions in Atherosclerosis Risk in the Communities. This population-based cohort recruited 15,792 individuals in 1987 to 1989 from four US communities and contained nine years of follow-up. Anemia was defined as hemoglobin <13.5 g/dL for men and <12 g/dL for women. Using a Cox Proportional Hazards model, we estimated the hazard ratio (HR) and confidence intervals (CI) of incident gout by baseline anemia, adjusted for confounders (sex, race, estimated glomerular filtration rate, body mass index and alcohol intake) and clinical factors (coronary heart disease, congestive heart failure, diabetes, hypertension, diuretic use and serum urate level). Among the 10,791 participants, 10% had anemia at baseline. There were 271 cases of incident gout. Patients with anemia had a two-fold increased risk of developing gout over nine years (HR = 2.01, 95% CI: 1.46, 2.76). Anemia was associated with incident gout independent of known gout risk factors, confounders and clinical risk factors (HR = 1.73, 95% CI: 1.24, 2.41). This association persisted after additionally adjusting for serum urate level (HR = 1.83, 95% CI: 1.30, 2.57). We identified anemia as a novel risk factor for gout. Anemia was associated with an approximately two-fold increased risk of gout-independent kidney function and serum urate. These findings suggest that anemia is a risk factor for gout on par with other chronic conditions such as obesity and diabetes. The biological mechanism linking anemia to gout remains unclear.

Efficacy of ABT-116, an antagonist of transient receptor potential vanilloid type 1, in providing analgesia for dogs with chemically induced synovitis.

PubMed

Cathcart, Curtis J; Johnston, Spencer A; Reynolds, Lisa R; Al-Nadaf, Sami; Budsberg, Steven C

2012-01-01

To investigate the ability of ABT-116 (a proprietary antagonist of transient receptor potential vanilloid type 1) administered at 2 doses to attenuate lameness in dogs with experimentally induced urate synovitis. 8 purpose-bred mixed-breed dogs. In a 4-way crossover study, dogs orally received each of low-dose ABT-116 treatment (LDA; 10 mg/kg), high-dose ABT-116 treatment (HDA; 30 mg/kg), firocoxib (5 mg/kg), and no treatment (nontreatment) once a day for 2 days, in a randomly assigned order. Synovitis was induced on the second day of each treatment period by intra-articular injection of either stifle joint with sodium urate, alternating between joints for each treatment period, beginning with the left stifle joint. Ground reaction forces, clinical lameness scores, and rectal temperature were assessed before the injection (baseline) and at various points afterward. Lameness scores at the 2-, 6-, and 12-hour assessment points were higher than baseline scores for HDA and nontreatment, whereas scores at the 2- and 6-hour points were higher than baseline scores for LDA. For firocoxib, there was no difference from baseline scores in lameness scores at any point. Compared with baseline values, peak vertical force and vertical impulse were lower at 2 and 6 hours for HDA and nontreatment and at 2 hours for LDA. No changes in these values were evident for firocoxib. The HDA or LDA resulted in higher rectal temperatures than did treatment with firocoxib or nothing, but those temperatures did not differ among treatments. HDA had no apparent effect on sodium urate-induced lameness; LDA did attenuate the lameness but not as completely as firocoxib treatment. High rectal temperature is an adverse effect of oral ABT-116 administration that may be of clinical concern.

Improved Gout Outcomes in Primary Care Using a Novel Disease Management Program: A Pilot Study.

PubMed

Bulbin, David; Denio, Alfred E; Berger, Andrea; Brown, Jason; Maynard, Carson; Sharma, Tarun; Kirchner, H Lester; Ayoub, William T

2018-02-13

To pilot a primary care gout management improvement intervention. Two large primary care sites were selected: one underwent the intervention, the other, a control, underwent no intervention. The intervention consisted of: engagement of intervention site staff, surveys of provider performance improvement preferences, and onsite live and enduring online education. Electronic Health Record reminders were constructed. Both the intervention and control sites had 3 quality measures assessed monthly: percent of gout patients treated with urate lowering therapy, percent of treated patients monitored with serum urate, and percent of treated patients at target serum urate ≤ 6.0 mg/dl. The intervention site providers received monthly reports comparing their measures against their peers. By 6 months, the intervention site significantly improved all 3 gout performance measures. Percentage treated increased from 54.4 to 61.1%, OR 1.19 (95% CI 1.08, 1.31 and p-value <0.001); percentage monitored increased from 56.1 to 79.2% OR 1.52 (95% CI 1.24, 1.87 and P-value <0.001); and percentage at goal increased from 26.8 to 43.3% OR 1.43 (95% CI 1.16, 1.77 and p-value <0.001. At 6 months after intervention, gout patients at the intervention site were more likely to be monitored (79.2% vs. 53.4%, OR 3.54 (95% CI: 2.30, 5.45 and p-value < 0.001)) and at goal (43.3% vs. 28.3%; OR 1.99 (95% CI: 1.33, 2.96 and p-value <0.001) than control site patients. Numbers treated did not significantly improve over the control site. A pilot multifaceted gout management program can significantly improve primary care gout management performance. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Relationship between Uric Acid Level and Achievement Motivation. Final Report.

ERIC Educational Resources Information Center

Mueller, Ernst F.; French, John R. P., Jr.

In an investigation of the relationship of uric acid (a metabolic end product) to achievement, this study hypothesized that a person's serum urate level (a factor often associated with gout) is positively related to achievement need as well as indicators of actual achievement. (Speed of promotion and number of yearly publications were chosen as…

Unpacking Your Study Abroad Experience: Critical Reflection for Workplace Competencies. Volume 1, Issue 1. CERI Research Brief 1-2008

ERIC Educational Resources Information Center

Gardner, Phil; Gross, Linda; Steglitz, Inge

2008-01-01

Colleges and universities are in competition to claim leadership in preparing students for a global world through participation in international experiences. Michigan State University (MSU) is often recognized as one of the leaders in study abroad, having woven the ethos of global education tightly into the core fabric of the university and…

Great Lakes Oil-In-Ice Demonstration 3

DTIC Science & Technology

2013-10-01

October 2013 3 - Alpena Community College - CG Marine Safety Unit (MSU) Duluth, MN 2.2 Demonstration Concept This demonstration focused on...Marine Sanctuary Gabe Schneider Regional Rep for US Senator Carl Levin Dr. Olin Joynton President, Alpena Community College David Cummins Marine...Technology Advisor, Alpena CC Don MacMaster Dean of Workforce Development, Alpena CC Adam Wojciehowski Response & Security Coordinator - U.S. Operations

A Proven Method for Cooperative Teaching Model between Universities and Public School Partnership Programs.

ERIC Educational Resources Information Center

Herbster, Douglas L.; And Others

A partnership was developed between the Bozeman (Montana) Public School District (BPSD) and the Montana State University (MSU) College of Education, Health, and Human Development. The purpose of the partnership was to foster collaboration between the two groups to improve the quality of K-12 education in the Bozeman District and to improve the…

A highly efficient machine planting system for forestry research plantations—the Wright-MSU method

Treesearch

James R. McKenna; Oriana Rueda-Krauss; Brian Beheler

2011-01-01

For forestry research purposes, grid planting with uniform tree spacing is superior to planting with nonuniform spacing because it controls density across the plantation and facilitates accurate repeat measurements. The ability to cross-check tree positions in a grid-type plantation avoids problems associated with dead or missing trees and increases the efficiency and...

Citations as Data: Harvesting the Scholarly Record of Your University to Enrich Institutional Knowledge and Support Research

ERIC Educational Resources Information Center

Sterman, Leila Belle; Clark, Jason A.

2017-01-01

Many research libraries are looking for new ways to demonstrate value for their parent institutions. Metrics, assessment, and promotion of research continue to grow in importance, but they have not always fallen into the scope of services for the research library. Montana State University (MSU) Library recognized a need and interest to quantify…

Strategies, Use, and Impact of Social Media for Supporting Teacher Community within Professional Development: The Case of One Urban STEM Program

ERIC Educational Resources Information Center

Rosenberg, Joshua M.; Greenhalgh, Spencer P.; Wolf, Leigh Graves; Koehler, Matthew J.

2017-01-01

This paper examines the use of social media to foster community connections within the MSU Urban Science, Technology, Engineering, and Mathematics (STEM) program. We describe the strategies employed by the program and the technologies employed by instructors to provide support, build community, and showcase learning. We highlight three particular…

Farming Systems Research: A Critical Appraisal. MSU Rural Development Paper No. 6.

ERIC Educational Resources Information Center

Gilbert, Elon H.; And Others

The objectives of the state-of-the-art paper, second in a series on farming systems research (FSR) in the Third World, are to: (1) review the literature on farming systems; (2) evaluate farming systems research in international institutes and in national agricultural research systems in the Third World; and (3) recommend what can be done to…

Satellite observations of a monsoon depression

NASA Technical Reports Server (NTRS)

Warner, C.

1984-01-01

The exploration of a monsoon depression over Burma and the Bay of Bengal is discussed. Aircraft and satellite data were examined, with an emphasis on the Microwave Sounding Unit (MSU) aboard TIROS-N and the Scanning Multichannel Microwave Radiometer (SMMR) aboard Nimbus-7. The structure of the monsoon depression was found to be dominated by cumulus convection. The only systematic large scale behavior discerned was a propagation of the depression westward, and diurnal migration of contours of brightness temperature. These contours in the middle troposphere showed a gradient toward the north with the patterns migrating northward at night. From SMMR and dropwindsonde data, water vapor contents were found to be near 65 mm, increasing to more than 70 mm in the northeast Bay of Bengal. Cloud water contents reached about three mm. Rainfall rates exceeding 5.7 mm/h occurred over a small part of the storm area, while mean rainfall rates in areas of order 20,000 sq km reached approximately 0.5 mm/h. Measured MSU brightness temperatures were reconciled very well with dropwindsonde data and with airborne in situ observations of clouds (by photography) and hydrometeors (by radar). Diffuse scattering was determined to be important in computing brightness temperature.

OceanNOMADS: A New Distribution Node for Operational Ocean Model Output

NASA Astrophysics Data System (ADS)

Cross, S.; Vance, T.; Breckenridge, T.

2009-12-01

The NOAA National Operational Model Archive and Distribution System (NOMADS) is a distributed, web-services based project providing real-time and retrospective access to climate and weather model data and related datasets. OceanNOMADS is a new NOMADS node dedicated to ocean model and related data, with an initial focus on operational ocean models from NOAA and the U.S. Navy. The node offers data access through a Thematic Real-time Environmental Distributed Data Services (THREDDS) server via the commonly used OPeNDAP protocol. The primary server is operated by the National Coastal Data Development Center and hosted by the Northern Gulf Institute at Stennis Space Center, MS. In cooperation with the National Marine Fisheries Service and Mississippi State University (MSU), a duplicate server is being installed at MSU with a 1-gigabit connection to the National Lambda Rail. This setup will allow us to begin to quantify the benefit of high-speed data connections to scientists needing remote access to these large datasets. Work is also underway on the next generation of services from OceanNOMADS, including user-requested server-side data reformatting, regridding, and aggregation, as well as tools for model-data comparison.

Understanding and Reconciling Differences in Surface and Satellite-Based Lower Troposphere Temperatures

NASA Astrophysics Data System (ADS)

Hausfather, Z.; Thorne, P.; Mears, C. A.

2017-12-01

One of the main remaining uncertainties in global temperatures over the past few decades is the disagreement between surface and microwave sounding unit (MSU) satellite-based observations of the lower troposphere. Reconciling these will prove an important step in improving our understanding of modern climate change, and help resolve an issue that has been frequently brought to the attention of policymakers and highlighted as a reason to distrust climate observations. To assess differences between surface and satellite records, we examine data from radiosondes, from atmospheric reanalysis, from numerous different satellites, from surface observations over the land and ocean, and from global climate models. Controlling for spatial coverage, we determine where these datasets agree and disagree, isolate the differences, and identify for common factors to explain the divergences. We find large systemic differences between surface and lower troposphere warming in MSU/AMSU records compared to radiosondes, reanalysis products, and climate models that suggest possible residual inhomogeneities in satellite records. We further show that no reasonable subset of surface temperature records exhibits as little warming over the last two decades as satellite observations, suggesting that inhomogeneities in the surface record are very likely not responsible for the divergence.

Design of a compact all-permanent magnet ECR ion source injector for ReA at the MSU NSCL

NASA Astrophysics Data System (ADS)

Pham, Alfonse N.; Leitner, Daniela; Glennon, Patrick; Ottarson, Jack; Lawton, Don; Portillo, Mauricio; Machicoane, Guillaume; Wenstrom, John; Lajoie, Andrew

2016-06-01

The design of a compact all-permanent magnet electron cyclotron resonance (ECR) ion source injector for the ReAccelerator Facility (ReA) at the Michigan State University (MSU) National Superconducting Cyclotron Laboratory (NSCL) is currently being carried out. The ECR ion source injector will complement the electron beam ion trap (EBIT) charge breeder as an off-line stable ion beam injector for the ReA linac. The objective of the ECR ion source injector is to provide continuous-wave beams of heavy ions from hydrogen to masses up to 136Xe within the ReA charge-to-mass ratio (Q / A) operational range from 0.2 to 0.5. The ECR ion source will be mounted on a high-voltage platform that can be adjusted to obtain the required 12 keV/u injection energy into a room temperature radio-frequency quadrupole (RFQ) for further acceleration. The beam line consists of a 30 kV tetrode extraction system, mass analyzing section, and optical matching section for injection into the existing ReA low energy beam transport (LEBT) line. The design of the ECR ion source and the associated beam line are discussed.

Effectiveness of a Web-Supplemented Astronomy Survey Course

NASA Astrophysics Data System (ADS)

Hufnagel, B.

1997-12-01

An astronomy survey course for \\ 200 non-science majors, offered in spring 1997 at Michigan State University, was supplemented with an internet site. Web access was voluntary, with the exception of about 10% of the homework problems. In addition, all of the answers to homeworks, in-class activities, and tests were available only on the website. The website included web versions of all the usual hard-copy handouts, as well as lecture notes, links to other astronomy URLs, and a frequently-asked question (FAQ) site taken from student email to the professors. MSU students can access the Web through \\ 30 PC labs on and off campus, and through private PCs in the dorms where most of the MSU students live. A mid-semester open-ended feedback form (for class credit) was administered in-class to the students, with 151 respondents. Their responses to the question ``About how frequently do you access the course website?'' will be correlated to their grade at that point in the course, their gender, and their purpose for accessing the website. These results will be interesting to astronomy teachers who would like to offer additional resources and more lines of communication to their students at low cost and without abandoning traditional methods.

Understanding tropical upper tropospheric warming: The role of SSTs, convective parameterizations, and observational uncertainties

NASA Astrophysics Data System (ADS)

Po-Chedley, S.; Thorsen, T. J.; Fu, Q.

2015-12-01

Recent research has compared CMIP5 general circulation model (GCM) simulations with satellite observations of warming in the tropical upper troposphere relative to the lower-middle troposphere. Although the pattern of SST warming is important, this research demonstrated that models overestimate increases in static stability between the mid- to upper- tropical troposphere, even when they are forced with historical sea surface temperatures. This discrepancy between satellite-borne microwave sounding unit measurements (MSU) and GCMs is important because it has implications for the strength of the lapse rate and water vapor feedback. The apparent model-observational difference for changes in static stability in the tropical upper troposphere represents an important problem, but it is not clear whether the difference is a result of common biases in GCMs, biases in observational datasets, or both. In this work, we will use GCM simulations to examine the importance of the spatial pattern of SST warming and different convective parameterizations in determining the lapse rate changes in tropical troposphere. We will also consider uncertainties in MSU satellite observations, including changes in the diurnal sampling of temperature and instrument calibration biases when comparing GCMs with the observed record.

Mississippi State University Cooling, Heating, and Power (Micro-CHP) and Bio-Fuel Center

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mago, Pedro; Newell, LeLe

2014-01-31

Between 2008 and 2014, the U.S. Department of Energy funded the MSU Micro-CHP and Bio-Fuel Center located at Mississippi State University. The overall objective of this project was to enable micro-CHP (micro-combined heat and power) utilization, to facilitate and promote the use of CHP systems and to educate architects, engineers, and agricultural producers and scientists on the benefits of CHP systems. Therefore, the work of the Center focused on the three areas: CHP system modeling and optimization, outreach, and research. In general, the results obtained from this project demonstrated that CHP systems are attractive because they can provide energy, environmental,more » and economic benefits. Some of these benefits include the potential to reduce operational cost, carbon dioxide emissions, primary energy consumption, and power reliability during electric grid disruptions. The knowledge disseminated in numerous journal and conference papers from the outcomes of this project is beneficial to engineers, architects, agricultural producers, scientists and the public in general who are interested in CHP technology and applications. In addition, more than 48 graduate students and 23 undergraduate students, benefited from the training and research performed in the MSU Micro-CHP and Bio-Fuel Center.« less

Fellows in the Middle: Fabulous Field Trips

NASA Astrophysics Data System (ADS)

West, Mary Lou

2008-05-01

Montclair State University's NSF GK-12 Program focuses on grades 7 and 8 in five urban public school districts in northern New Jersey. Each year four fieldtrips are taken by the students, middle school teachers, and graduate student Fellows. Many interdisciplinary hands-on lessons are written for use before, during and after each trip with this year's theme of Earth history. The Sterling Hill Mine trip evoked lessons on geology, economics, crystal structure, density, and pH. A virtual trip (webcam link) to scientists in the rainforest of Panama prompted critical thinking, categorizing layers and animals, and construction of model food webs. In the field trip to the NJ School of Conservation the students will build model aquifers, measure tree heights, and measure stream flow to compare to their Hackensack River. Finally the students will travel to MSU for a Math/Science Day with research talks, lab tours, hands-on activities, and a poster session. In January 2008 seventeen teachers, Fellows, and grant personnel took a field trip to China to set up collaborations with researchers and schools in Beijing and Xi'an, including the Beijing Ancient Observatory. All field trips are fabulous! Next year (IYA) our theme will be planetary science and will feature field trips to the Newark Museum's Dreyfuss Planetarium, BCC Buehler Challenger & Science Center, and star parties. We look forward to invigorating middle school science and mathematics with exciting astronomy. Funded by NSF #0638708

Rotating Detonation Engine Research at NRL

DTIC Science & Technology

2013-07-01

Bykovskii, Wolanski, Falempin, Hayashi, Schauer, Yi, Wang, Brophy, Wu, Clafin, Smith, Tsuboi, Frolov, et al.) Recant RDE Studies at NRL Flow-field...Symposium) Injection/inflow effects (JPC 2011~044; ASM 2012-0617, ASM 2013-1178) the expansion region change RDE performance. Can this model be...Efficient Complex Configuration Simulation Capability 158 BASELINE SOLUTION • Basetine configUration Stoichiometric hydrogen-air RDE of Wolanski

Optical/IR Products - Naval Oceanography Portal

Science.gov Websites

are here: Home › USNO › Astrometry › Optical/IR Products USNO Logo USNO Navigation Optical/IR VLBI-based Products Astrometry Information Center Info Optical/IR Products Access to astrometric 2012. A poster paper describing the progress of URAT was presented at the April 2014 DDA meeting in

Photoexcitations in Polyacetylene.

DTIC Science & Technology

1981-11-11

Philadelphia, PA 19104 INov ~e!f M 81 Reproduction in whole or in part is permitted for any purpose of the United States Government Approved for public...substrates. Experiments utilized primarily the surface cell config- uration using ohmic contacts; similar results were obtained using sandwich cells ...resembles the photovoltaic quantum efficiency obtained from junction studies 5 with trans-(CH) . Thus, the photoresponse shown in Fig. 9 is genuine

Nonlinear Elasticity of Doped Semiconductors

DTIC Science & Technology

2017-02-01

experimental data from the Stanford University group. The obtained results show that the goal of the project has been reached. MSU has full...length extension modes in n-doped silicon (Si) microelectromechanical (MEMS) resonators and have started a comparison with the experimental data from...coupling to shear strain modes. • Tested the theory against the existing in the literature experimental data on the effect of doping on the speed of

MSU Medical Colleges Blended Learning for First Year Science Courses: Uniting Pedagogy to Maximize Experience and Real World Limitations

ERIC Educational Resources Information Center

Lovell, Kathryn; Vignare, Karen

2009-01-01

At Michigan State University the two medical schools, College of Human Medicine (CHM; M.D. degree) and College of Osteopathic Medicine (COM; D.O. degree), have offered the same science courses to first year students for many years. Science departments report to both colleges, and the same faculty can effectively teach the content required in the…

The Relation between Academic Aptitude and Commitment to Teaching among MSU Students. Research and Evaluation in Teacher Education. Program Evaluation Series No. 5.

ERIC Educational Resources Information Center

Byers, Joe L.

An overview and analysis is presented of the Vance and Schlechty Study (1982) of education majors which indicated that there is a negative selection process which systematically attracts and holds in the teaching profession young people with modest verbal and mathematical abilities. Three factors, operating singly or in combination, were…

The Design and Implementation of a Peer Mentoring Program for International Students at Morehead State University

ERIC Educational Resources Information Center

Murray, Donell Cochran

2017-01-01

Peer mentoring is a way to help guide and form valuable relationships between two or more students and plays an important role in the success, both academically and socially, of students. At Morehead State University (MSU), the International Peer Mentoring Program (IPMP) was designed and implemented in the Fall of 2016 to assist in the academic…

33 CFR 3.40-15 - Sector New Orleans Marine Inspection Zone and Captain of the Port Zone; Marine Safety Unit Morgan...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Inspection Zone and Captain of the Port Zone; Marine Safety Unit Morgan City. 3.40-15 Section 3.40-15... Morgan City. Sector New Orleans' office is located in New Orleans, LA. A subordinate unit, Marine Safety Unit (MSU) Morgan City, is located in Morgan City, LA. (a) Sector New Orleans' Marine Inspection Zone...

33 CFR 3.40-15 - Sector New Orleans Marine Inspection Zone and Captain of the Port Zone; Marine Safety Unit Morgan...

Code of Federal Regulations, 2011 CFR

2011-07-01

... Inspection Zone and Captain of the Port Zone; Marine Safety Unit Morgan City. 3.40-15 Section 3.40-15... Morgan City. Sector New Orleans' office is located in New Orleans, LA. A subordinate unit, Marine Safety Unit (MSU) Morgan City, is located in Morgan City, LA. (a) Sector New Orleans' Marine Inspection Zone...