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[PMID]:28786993
[Au] Autor:Tanaka T; Milaneschi Y; Zhang Y; Becker KG; Zukley L; Ferrucci L
[Ad] Endereço:Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland, United States of America.
[Ti] Título:A double blind placebo controlled randomized trial of the effect of acute uric acid changes on inflammatory markers in humans: A pilot study.
[So] Source:PLoS One;12(8):e0181100, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Uric acid has been linked with increased risk of chronic disease such as cardiovascular disease and this association has been attributed to a pro-inflammatory effect. Indeed, observational studies have shown that high uric acid is associated with high level of pro-inflammatory cytokines in the blood. However, whether high uric acid directly affects inflammation or rather represents a parallel defensive antioxidant mechanism in response to pathology that causes inflammation is unknown. To determine whether acute increase or decrease uric acid levels affects inflammation in healthy individuals, a randomized, placebo-controlled, double blind clinical study of uric acid or rasburicase with 20 healthy volunteers in each treatment-placebo group was conducted at the National Institute on Aging (NIA) Clinical Research Unit (CRU) at Harbor Hospital in Baltimore, MD. Change in inflammatory response was assessed by administering an oral lipid tolerance before and after the treatment of uric acid, rasburicase and placebo. Following uric acid administration, there was an accentuated increase in IL-6 during the oral lipid tolerance test (P<0.001). No significant differences were observed after lowering of uric acid with rasburicase. No side effects were reported throughout the trial. In health individuals, acute increase in uric acid results in an increased IL-6 response when challenged with lipid load. Such effect of amplification of inflammatory response may explain the higher risk of chronic diseases observed in subclinical hyperuricemia in observational studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT01323335.
[Mh] Termos MeSH primário: Interleucina-6/sangue
Urato Oxidase/farmacologia
Ácido Úrico/sangue
Ácido Úrico/farmacologia
[Mh] Termos MeSH secundário: Biomarcadores/sangue
Método Duplo-Cego
Feminino
Expressão Gênica/efeitos dos fármacos
Seres Humanos
Inflamação/sangue
Lipídeos/administração & dosagem
Masculino
Análise em Microsséries
Meia-Idade
Projetos Piloto
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Biomarkers); 0 (IL6 protein, human); 0 (Interleukin-6); 0 (Lipids); 268B43MJ25 (Uric Acid); EC 1.7.3.3 (Urate Oxidase); EC 1.7.3.3 (rasburicase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170809
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181100


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[PMID]:28594873
[Au] Autor:Szczurek P; Mosiichuk N; Wolinski J; Yatsenko T; Grujic D; Lozinska L; Pieszka M; Swiech E; Pierzynowski SG; Goncharova K
[Ad] Endereço:Department of Biology, Lund University, Lund, Sweden.
[Ti] Título:Oral uricase eliminates blood uric acid in the hyperuricemic pig model.
[So] Source:PLoS One;12(6):e0179195, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:An elevated level of serum uric acid-hyperuricemia, is strongly associated with the development of gout and chronic kidney disease (CKD) which is often accompanied by a significantly reduced glomerular filtration rate (GFR). In the present study, we investigated the extra-renal elimination of uric acid via the intestine in a healthy pig model and the effect of oral uricase therapy on plasma uric acid concentrations in pigs with induced hyperuricemia and CKD. The experiment was conducted on eleven, ten-week-old pigs (n = 11). The porcine model of CKD was developed by performing 9/10 nephrectomy surgery on eight pigs. A stable model of hyperuricemia was established in only five of the eight nephrectomized pigs by frequent injections of uric acid (UA) into the jugular vein. All pigs (three healthy pigs and five CKD pigs) were operated for implantation of jugular vein catheters and the three healthy pigs also had portal vein catheters inserted. Blood uric acid concentrations were measured spectrophotometrically, using the Uric Acid Assay Kit (BioAssay Systems, Hayward, USA). The piglets with CKD received orally administered uricase (treatment) and served as their own controls (without uricase supplementation). Oral uricase therapy significantly decreased plasma uric acid concentrations in pigs with CKD, whereas hyperuricemia was observed in the pigs whilst not being treated with uricase. Urinary uric acid excretion was similar during both the treatment and control periods during the first 8 h and 24 h after UA infusions in the CKD pigs. To demonstrate the elimination of UA via the intestine, the healthy pigs were infused with UA into the jugular vein. The blood collected from the jugular vein represents circulating UA concentrations and the blood collected from the portal vein represents the concentration of UA leaving the intestine. The final (after 2 h) concentration of UA was significantly lower in blood collected from the portal vein compared to that collected from the jugular vein (3.34 vs. 2.43 mg/dL, respectively, p = 0.024). The latter allows us to suggest that UA is eliminated from the blood via the gut tissue.
[Mh] Termos MeSH primário: Hiperuricemia/sangue
Hiperuricemia/tratamento farmacológico
Urato Oxidase/administração & dosagem
Urato Oxidase/uso terapêutico
Ácido Úrico/sangue
[Mh] Termos MeSH secundário: Administração Oral
Animais
Modelos Animais de Doenças
Hiperuricemia/complicações
Hiperuricemia/urina
Intestinos/metabolismo
Masculino
Nefrectomia
Insuficiência Renal Crônica/sangue
Insuficiência Renal Crônica/complicações
Insuficiência Renal Crônica/urina
Sus scrofa
Ácido Úrico/urina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
268B43MJ25 (Uric Acid); EC 1.7.3.3 (Urate Oxidase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170609
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179195


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[PMID]:28531234
[Au] Autor:Li W; Xu S; Zhang B; Zhu Y; Hua Y; Kong X; Sun L; Hong J
[Ad] Endereço:School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, P. R. China.
[Ti] Título:Directed evolution to improve the catalytic efficiency of urate oxidase from Bacillus subtilis.
[So] Source:PLoS One;12(5):e0177877, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Urate oxidase is a key enzyme in purine metabolism and catalyzes the oxidation of uric acid to allantoin. It is used to treat hyperuricemia and gout, and also in a diagnostic kit. In this study, error-prone polymerase chain reaction and staggered extension process was used to generate a mutant urate oxidase with improved enzyme activity from Bacillus subtilis. After several rounds of mutagenesis and screening, two mutants 6E9 and 8E279 were obtained which exhibited 2.99 and 3.43 times higher catalytic efficiency, respectively. They also exhibited lower optimal reaction temperature and higher thermo-stability. D44V, Q268R and K285Q were identified as the three most beneficial amino acid substitutions introduced by site-directed mutagenesis. D44V/Q268R, which was obtained through random combination of the three mutants, displayed the highest catalytic activity. The Km, kcat/Km and enzyme activity of D44V/Q268R increased by 68%, 83% and 129% respectively, compared with that of wild-type urate oxidase. Structural modeling indicated that mutations far from the active site can have significant effects on activity. For many of them, the underlying mechanisms are still difficult to explain from the static structural model. We also compared the effects of the same set of single point mutations on the wild type and on the final mutant. The results indicate strong effects of epistasis, which may imply that the mutations affect catalysis through influences on protein dynamics besides equilibrium structures.
[Mh] Termos MeSH primário: Substituição de Aminoácidos
Bacillus subtilis/enzimologia
Evolução Molecular Direcionada/métodos
Urato Oxidase/genética
Urato Oxidase/metabolismo
[Mh] Termos MeSH secundário: Bacillus subtilis/genética
Proteínas de Bactérias/química
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Biocatálise
Domínio Catalítico
Estabilidade Enzimática
Epistasia Genética
Cinética
Modelos Moleculares
Mutagênese Sítio-Dirigida
Conformação Proteica
Temperatura Ambiente
Urato Oxidase/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); EC 1.7.3.3 (Urate Oxidase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170908
[Lr] Data última revisão:
170908
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170523
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0177877


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[PMID]:28526525
[Au] Autor:Yang X; Feng Y; Chong H; Wang D; Hu X; Pu J; Zhan CG; Liao F
[Ad] Endereço:Unit for Analytical Probes and Protein Biotechnology, Key Laboratory of Medical Laboratory Diagnostics of the Education Ministry, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
[Ti] Título:High-throughput estimation of specific activities of enzyme/mutants in cell lysates through immunoturbidimetric assay of proteins.
[So] Source:Anal Biochem;534:91-98, 2017 Oct 01.
[Is] ISSN:1096-0309
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:High-throughput estimation of specific activities of an enzyme and its mutants in a group (enzyme/mutants) in cell lysates via high-throughput assay of their activities and separate immunoturbidimetric assay (ITA) of their proteins was proposed. Pseudomonas aeruginosa arylsulfatase (PAAS) and Bacillus fastidious uricase (BFU) served as two models. ITA employed 0.75 mg of antisera against PAAS or BFU as the reference in 96-well microplates to measure the difference of extinction at 340 and 700 nm. According to the calibration curve, ITA quantified the reference from 0.40 to about 2.4 µg. The consistency among the abundance of enzyme/mutants through ITA of proteins in cell lysates prepared under the same conditions supported their consistent immunological reactivity to the antisera. Specific activities of PAAS/mutants or BFU/mutants in cell lysates through ITA of proteins showed excellent proportionality to those carefully determined after purification. Receiver-operating-characteristic (ROC) analysis of specific activities through ITA of proteins gave a higher area-under-curve than those for ROC analyses of other activity indices, which allowed the recognition of a PAAS/mutant of 50% higher activity after cell amplification in high-throughput mode. Therefore, ITA of enzyme/mutants as proteins is promising to estimate their specific activities in cell lysates in high-throughput mode for quantitative comparison.
[Mh] Termos MeSH primário: Arilsulfatases/análise
Ensaios de Triagem em Larga Escala
Técnicas Imunoenzimáticas
Urato Oxidase/análise
[Mh] Termos MeSH secundário: Arilsulfatases/genética
Arilsulfatases/metabolismo
Bacillus/citologia
Bacillus/enzimologia
Mutação
Nefelometria e Turbidimetria
Pseudomonas aeruginosa/citologia
Pseudomonas aeruginosa/enzimologia
Urato Oxidase/genética
Urato Oxidase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 1.7.3.3 (Urate Oxidase); EC 3.1.6.1 (Arylsulfatases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170821
[Lr] Data última revisão:
170821
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170521
[St] Status:MEDLINE


  5 / 1406 MEDLINE  
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[PMID]:28379501
[Au] Autor:Zhang T; Pope JE
[Ad] Endereço:Department of Rheumatology, Schulich School of Medicine & Dentistry, Western University of Canada, St Joseph Health Care, London, ON Canada.
[Ti] Título:Cardiovascular effects of urate-lowering therapies in patients with chronic gout: a systematic review and meta-analysis.
[So] Source:Rheumatology (Oxford);56(7):1144-1153, 2017 Jul 01.
[Is] ISSN:1462-0332
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Objectives: To determine if urate-lowering treatment (ULT) in gout can reduce cardiovascular (CV) outcomes. Methods: Randomized trials were searched for treatment with ULT in gout. Eligible trials had to report CV safety of a ULT. Potential medications included allopurinol, febuxostat, pegloticase, rasburicase, probenecid, benzbromarone, sulphinpyrazone, losartan, fenofibrate and sodium-glucose linked transporter 2 inhibitors. Results: A total of 3084 citations were found, with 642 duplicates. After the primary screen, 35 studies were selected for review. Several trials did not report CV events. Six were not randomized controlled trials (RCTs). Four studies reported no events in either intervention arm while the other four had 40 events in the febuxostat group ( n = 3631) and 5 in allopurinol group ( n = 1154). Overall, the pooled analysis did not show a significant difference between the two [febuxostat vs allopurinol: relative risk (RR) 1.69 (95% CI 0.54, 5.34), P = 0.37]. CV events did not decrease over time. Comparing shorter studies (<52 weeks) to longer ones did not reveal any statistical differences. However, in long-term studies with febuxostat vs allopurinol, results were nearly significant, with more CVE occurring with febuxostat treatment. Comparing any ULT to placebo (eight studies, n = 2221 patients) did not demonstrate a significant difference in non-Anti-Platelet Trialists' Collaboration events [any ULT vs placebo: RR 1.47 (95% CI 0.49, 4.40), P = 0.49] or all-cause mortality [any ULT vs placebo: RR 1.45 (95% CI 0.35, 5.77), P = 0.60]. Conclusion: RCT data do not suggest differences in CV events among ULTs in gout. Trials had few events despite high-risk patients being enrolled and may have been too short to show CV reduction by controlling inflammatory attacks and lowering uric acid.
[Mh] Termos MeSH primário: Doenças Cardiovasculares/prevenção & controle
Supressores da Gota/uso terapêutico
Gota/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Alopurinol/uso terapêutico
Artrite Gotosa/diagnóstico
Artrite Gotosa/tratamento farmacológico
Doença Crônica
Febuxostat/uso terapêutico
Feminino
Gota/diagnóstico
Seres Humanos
Masculino
Meia-Idade
Polietilenoglicóis/uso terapêutico
Prognóstico
Ensaios Clínicos Controlados Aleatórios como Assunto
Resultado do Tratamento
Urato Oxidase/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Gout Suppressants); 101V0R1N2E (Febuxostat); 30IQX730WE (Polyethylene Glycols); 63CZ7GJN5I (Allopurinol); EC 1.7.3.3 (Urate Oxidase); R581OT55EA (Pegloticase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170406
[St] Status:MEDLINE
[do] DOI:10.1093/rheumatology/kex065


  6 / 1406 MEDLINE  
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[PMID]:28337250
[Au] Autor:Asakawa S; Shibata S; Morimoto C; Shiraishi T; Nakamura T; Tamura Y; Kumagai T; Hosoyamada M; Uchida S
[Ad] Endereço:Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
[Ti] Título:Podocyte Injury and Albuminuria in Experimental Hyperuricemic Model Rats.
[So] Source:Oxid Med Cell Longev;2017:3759153, 2017.
[Is] ISSN:1942-0994
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Although hyperuricemia is shown to accelerate chronic kidney disease, the mechanisms remain unclear. Accumulating studies also indicate that uric acid has both pro- and antioxidant properties. We postulated that hyperuricemia impairs the function of glomerular podocytes, resulting in albuminuria. Hyperuricemic model was induced by oral administration of 2% oxonic acid, a uricase inhibitor. Oxonic acid caused a twofold increase in serum uric acid levels at 8 weeks when compared to control animals. Hyperuricemia in this model was associated with the increase in blood pressure and the wall-thickening of afferent arterioles as well as arcuate arteries. Notably, hyperuricemic rats showed significant albuminuria, and the podocyte injury marker, desmin, was upregulated in the glomeruli. Conversely, podocin, the key component of podocyte slit diaphragm, was downregulated. Structural analysis using transmission electron microscopy confirmed podocyte injury in this model. We found that urinary 8-hydroxy-2'-deoxyguanosine levels were significantly increased and correlated with albuminuria and podocytopathy. Interestingly, although the superoxide dismutase mimetic, tempol, ameliorated the vascular changes and the hypertension, it failed to reduce albuminuria, suggesting that vascular remodeling and podocyte injury in this model are mediated through different mechanisms. In conclusion, vasculopathy and podocytopathy may distinctly contribute to the kidney injury in a hyperuricemic state.
[Mh] Termos MeSH primário: Albuminúria/complicações
Hiperuricemia/patologia
[Mh] Termos MeSH secundário: Actinas/metabolismo
Animais
Pressão Sanguínea/efeitos dos fármacos
Óxidos N-Cíclicos/farmacologia
Desoxiguanosina/análogos & derivados
Desoxiguanosina/urina
Desmina/metabolismo
Modelos Animais de Doenças
Hiperuricemia/induzido quimicamente
Hiperuricemia/complicações
Imuno-Histoquímica
Glomérulos Renais/efeitos dos fármacos
Glomérulos Renais/metabolismo
Masculino
Microscopia Eletrônica de Transmissão
Estresse Oxidativo/efeitos dos fármacos
Ácido Oxônico/farmacologia
Ratos
Ratos Sprague-Dawley
Marcadores de Spin
Urato Oxidase/antagonistas & inibidores
Urato Oxidase/metabolismo
Ácido Úrico/sangue
Xantina Desidrogenase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Actins); 0 (Cyclic N-Oxides); 0 (Desmin); 0 (Spin Labels); 0 (smooth muscle actin, rat); 268B43MJ25 (Uric Acid); 5VT6420TIG (Oxonic Acid); 88847-89-6 (8-oxo-7-hydrodeoxyguanosine); EC 1.17.1.4 (Xanthine Dehydrogenase); EC 1.7.3.3 (Urate Oxidase); G9481N71RO (Deoxyguanosine); U78ZX2F65X (tempol)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170420
[Lr] Data última revisão:
170420
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170325
[St] Status:MEDLINE
[do] DOI:10.1155/2017/3759153


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[PMID]:28335813
[Au] Autor:Catania VE; Vecchio M; Malaguarnera M; Madeddu R; Malaguarnera G; Latteri S
[Ad] Endereço:Department of Medical-Surgical Sciences, and Advanced Technologies "G. F. Ingrassia", University of Catania, via Santa Sofia 86, 95123, Catania, Italy. vito.catania@policlinico.unict.it.
[Ti] Título:Tumor lysis syndrome in an extraskeletal osteosarcoma: a case report and review of the literature.
[So] Source:J Med Case Rep;11(1):79, 2017 Mar 24.
[Is] ISSN:1752-1947
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: This case report describes a spontaneous tumor lysis syndrome due to a rare solid tumor. CASE PRESENTATION: A 65-year-old white woman had tumor lysis syndrome, which represent a dangerous oncological emergency. This syndrome occurs usually with a hematological tumor, but in this case our patient had a solid tumor, which was a rare extraskeletal osteosarcoma, localized in her pelvic region. She also had lung metastases and bilateral hydronephrosis. After spontaneous tumor lysis syndrome, she had acute renal insufficiency, which was treated with hemodialysis and successively with rasburicase, Kayexalate (sodium polystyrene sulfonate), and febuxostat. CONCLUSION: Tumor lysis syndrome represents an oncological emergency, which must be suspected and treated as soon as possible.
[Mh] Termos MeSH primário: Lesão Renal Aguda/diagnóstico
Antineoplásicos/uso terapêutico
Neoplasias Ósseas/diagnóstico
Osteossarcoma/diagnóstico
Neoplasias Peritoneais/diagnóstico
Síndrome de Lise Tumoral/diagnóstico
Urato Oxidase/uso terapêutico
[Mh] Termos MeSH secundário: Dor Abdominal/etiologia
Lesão Renal Aguda/terapia
Idoso
Neoplasias Ósseas/patologia
Neoplasias Ósseas/terapia
Feminino
Supressores da Gota/uso terapêutico
Seres Humanos
Osteossarcoma/patologia
Osteossarcoma/terapia
Neoplasias Peritoneais/patologia
Neoplasias Peritoneais/terapia
Diálise Renal
Resultado do Tratamento
Síndrome de Lise Tumoral/patologia
Síndrome de Lise Tumoral/terapia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Gout Suppressants); EC 1.7.3.3 (Urate Oxidase); EC 1.7.3.3 (rasburicase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170325
[St] Status:MEDLINE
[do] DOI:10.1186/s13256-017-1241-3


  8 / 1406 MEDLINE  
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[PMID]:28302963
[Au] Autor:Tang DH; Ye YS; Wang CY; Li ZL; Zheng H; Ma KL
[Ad] Endereço:Medical Primate Research Center of China, Institute of Medical Biology, Chinese Academy of Medical Sciences/Peking Union Medical College, No. 935, Jiaoling Road, Kunming, Yunnan 650118, P.R. China.
[Ti] Título:Potassium oxonate induces acute hyperuricemia in the tree shrew (tupaia belangeri chinensis).
[So] Source:Exp Anim;66(3):209-216, 2017 Aug 05.
[Is] ISSN:1881-7122
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Potassium oxonate, a selectively competitive uricase inhibitor, produced hyperuricemia (HUA) in rodents in a previous study. In this study, we employed the tree shrew as an animal model to study potassium oxonate-induced HUA. The effect of allopurinol (ALLO), a uric acid reducer, was also examined in this model. Potassium oxonate at doses of 5, 20, 40, 60, 80, 100, and 1,000 mg/kg was given intraperitoneally to tree shrews. The results showed that potassium oxonate can effectively increase the levels of uric acid in tree shrews at doses ranging from 40 to 100 mg/kg. Semiquantitative RT-PCR showed that the xanthine dehydrogenase/oxidase (XDH/XO) mRNA expression level was significantly higher in the liver tissue of tree shrews with high levels of uric acid. There were no changes in serum urea nitrogen, or serum creatinine values. ALLO can significantly decrease serum uric acid levels (P<0.01) and raise XDH/XO mRNA expression levels in the liver tissue of tree shrews with HUA. XDH/XO mRNA expression levels did not change in untreated tree shrews. Studies on acute toxicity in the tree shrew did not show any significantly abnormal signs. There were no adverse effects at the macroscopic level up to doses ≤100 mg/kg. Potassium oxonate induced acute HUA in tree shrews at lower doses compared with other animal models. Potassium oxonate-treated tree shrews may be a potential animal model for studying pathogenic mechanism and evaluating a new therapeutic agent for treatment of HUA in humans.
[Mh] Termos MeSH primário: Modelos Animais de Doenças
Inibidores Enzimáticos/efeitos adversos
Hiperuricemia/induzido quimicamente
Ácido Oxônico/efeitos adversos
Tupaia
[Mh] Termos MeSH secundário: Doença Aguda
Alopurinol/farmacologia
Alopurinol/uso terapêutico
Animais
Relação Dose-Resposta a Droga
Inibidores Enzimáticos/administração & dosagem
Expressão Gênica
Seres Humanos
Hiperuricemia/tratamento farmacológico
Injeções Intraperitoneais
Fígado/metabolismo
Ácido Oxônico/administração & dosagem
RNA Mensageiro/metabolismo
Urato Oxidase/antagonistas & inibidores
Ácido Úrico/metabolismo
Xantina Desidrogenase/genética
Xantina Desidrogenase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (RNA, Messenger); 268B43MJ25 (Uric Acid); 4R7FFA00RX (potassium oxonate); 5VT6420TIG (Oxonic Acid); 63CZ7GJN5I (Allopurinol); EC 1.17.1.4 (Xanthine Dehydrogenase); EC 1.7.3.3 (Urate Oxidase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170318
[St] Status:MEDLINE
[do] DOI:10.1538/expanim.16-0096


  9 / 1406 MEDLINE  
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[PMID]:28272834
[Au] Autor:Cheuk DK; Chiang AK; Chan GC; Ha SY
[Ad] Endereço:Department of Pediatrics and Adolescent Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China.
[Ti] Título:Urate oxidase for the prevention and treatment of tumour lysis syndrome in children with cancer.
[So] Source:Cochrane Database Syst Rev;3:CD006945, 2017 03 08.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: 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. OBJECTIVES: To assess the effects and safety of urate oxidase for the prevention and treatment of TLS in children with malignancies. SEARCH METHODS: 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. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: 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. MAIN RESULTS: 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. AUTHORS' CONCLUSIONS: 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.
[Mh] Termos MeSH primário: Neoplasias/tratamento farmacológico
Síndrome de Lise Tumoral/prevenção & controle
Urato Oxidase/uso terapêutico
[Mh] Termos MeSH secundário: Adolescente
Alopurinol/uso terapêutico
Antimetabólitos/uso terapêutico
Área Sob a Curva
Criança
Ensaios Clínicos Controlados como Assunto
Seres Humanos
Ensaios Clínicos Controlados Aleatórios como Assunto
Insuficiência Renal/prevenção & controle
Síndrome de Lise Tumoral/mortalidade
Ácido Úrico/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Antimetabolites); 268B43MJ25 (Uric Acid); 63CZ7GJN5I (Allopurinol); EC 1.7.3.3 (Urate Oxidase); EC 1.7.3.3 (rasburicase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170309
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD006945.pub4


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[PMID]:28235562
[Au] Autor:Baumann A; Skaljac M; Lehmann R; Vilcinskas A; Franta Z
[Ad] Endereço:Department of Bioresources, Fraunhofer Institute for Molecular Biology and Applied Ecology, Winchesterstraße 2, 35394 Giessen, Germany.
[Ti] Título:Urate Oxidase produced by Lucilia sericata medical maggots is localized in Malpighian tubes and facilitates allantoin production.
[So] Source:Insect Biochem Mol Biol;83:44-53, 2017 Apr.
[Is] ISSN:1879-0240
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Lucilia sericata maggots are the only species currently approved for maggot debridement therapy (MDT), an alternative treatment for chronic and recalcitrant wounds. Maggots promote wound debridement, disinfection and healing by producing a complex mixture of proteins, peptides and low-molecular-weight compounds in their secretions and excretions, but the individual components are not well characterized at the molecular level. Here we investigated the purine catabolism pathway in L. sericata, focusing on the production of allantoin by Urate Oxidase (UO), which is thought to promote wound healing. We produced recombinant L. sericata UO in Escherichia coli, and characterized the properties of the pure enzyme in terms of the optimum pH (7-10) and temperature (20-25 °C), its stability, sensitivity to inhibition and ion dependency. We used quantitative RT-PCR and RNA in situ hybridization to monitor the expression of the UO gene, and we used a guinea pig anti-UO antibody to detect the native enzyme by western blot and by florescence immunohistochemistry in larval tissues. We found that L. sericata UO is exclusively present in the larval excretion organ (the Malpighian tubes) and is freely available in the cytoplasm rather than restricted to a specific subcellular compartment. Allantoin is a final product of L. sericata purine catabolism. It is produced by UO in the Malpighian tubes to remove uric acid from the hemolymph and is consequently excreted via the hindgut. Our findings confirm the hypothesis that both actively secreted molecules and excretion products contribute to the beneficial effects of MDT.
[Mh] Termos MeSH primário: Alantoína/metabolismo
Dípteros/enzimologia
Túbulos de Malpighi/metabolismo
Urato Oxidase/metabolismo
[Mh] Termos MeSH secundário: Animais
Larva/enzimologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
344S277G0Z (Allantoin); EC 1.7.3.3 (Urate Oxidase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170822
[Lr] Data última revisão:
170822
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170226
[St] Status:MEDLINE



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