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1.
Lancet Haematol ; 7(2): e168-e176, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32004486

RESUMO

Tumour lysis syndrome is a complication of chemotherapy for haematological malignancies; in particular, aggressive leukaemias and lymphomas. For haematological malignancies, targeted therapies, such as small molecule inhibitors and monoclonal antibodies, have a high anti-tumour activity, are well tolerated, and have a low incidence of associated tumour lysis syndrome. The BCL-2 inhibitor venetoclax has a high anti-tumour activity in chronic lymphocytic leukaemia, achieving deep remissions by potently inducing apoptosis and increasing the risk for tumour lysis syndrome. In this Viewpoint, we discuss the pathophysiology, risk factors, monitoring, changes in laboratory parameters, and clinical manifestations of tumour lysis syndrome, and the prophylaxis and treatments available for this complication. Prophylaxis and treatment strategies have been implemented as standard of care in patients receiving venetoclax to minimise the risk of both laboratory and clinical manifestations of tumour lysis syndrome.


Assuntos
Antineoplásicos/efeitos adversos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Terapia de Alvo Molecular/efeitos adversos , Proteínas de Neoplasias/antagonistas & inibidores , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Síndrome de Lise Tumoral/etiologia , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/terapia , Alopurinol/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/etiologia , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Sinergismo Farmacológico , Humanos , Hiperfosfatemia/etiologia , Hiperfosfatemia/terapia , Hiperuricemia/tratamento farmacológico , Hiperuricemia/etiologia , Leucemia Linfocítica Crônica de Células B/enzimologia , Diálise Renal , Fatores de Risco , Índice de Gravidade de Doença , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Síndrome de Lise Tumoral/diagnóstico , Síndrome de Lise Tumoral/tratamento farmacológico , Síndrome de Lise Tumoral/prevenção & controle , Urato Oxidase/uso terapêutico
2.
Medicine (Baltimore) ; 99(2): e18542, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914028

RESUMO

OBJECTIVE: Gout and hyperuricemia are common public health problem. There has been no epidemiological survey of gout and hyperuricemia in Tibet Autonomous Region, the southwest of China. Therefore, we estimated the prevalence of gout and hyperuricemia in Luoma Town, Naqu City, Tibet Autonomous Region of China. METHODS: A population-based cross-sectional survey was conducted among 1458 residents of Luoma Town, Tibet Autonomous Region, age ≥40 years. We used questionnaires in face-to-face interviews, anthropometric measurements and serum uric acid test. Hyperuricemia was defined as serum uric acid level ≥7 mg/dl in men and ≥6 mg/dl in women. The definition of gout in this study was on the basis of new 2015ACR/EULAR classification criteria. RESULTS: Nine hundred eighty-nine participants completed all items of gout and 818 participants attended to be taken blood samples for serum UA levels test. The overall crude prevalence of gout and hyperuricemia was 0.30% and 1.83% respectively. It was more prevalent in men than in women (2.86% vs 0.75%, P = .034) in hyperuricemia group. Tibetan had a lower age-standardized prevalence of gout 0.26% (95% confidence interval (CI): 0%-0.60%) and hyperuricemia 2.05% (95% confidence interval (CI): 0.99%-3.44%) compared with the China Health and Retirement Longitudinal Study results. CONCLUSION: This is the first large-scale population-based survey to demonstrate the prevalence of gout and hyperuricemia of the middle-aged and elderly population in Tibet Autonomous Region, China. The prevalence of gout and hyperuricemia is relatively lower than other places in China, and that might be influenced by ethnicity, genetic and environment factors. These findings will be useful for the future researches and health care strategies.


Assuntos
Gota/epidemiologia , Hiperuricemia/epidemiologia , Ácido Úrico/sangue , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Tibet
3.
Int J Clin Pharmacol Ther ; 58(1): 21-28, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31657714

RESUMO

OBJECTIVE: Febuxostat, a novel non-purine selective xanthine oxidase inhibitor, is a recommended treatment option for patients with chronic kidney disease (CKD) and hyperuricemia. There are only a few trials on the long-term use of allopurinol and febuxostat for CKD. In this study, we compared the efficacy of allopurinol and febuxostat and their effects on renal function in patients with CKD and hyperuricemia. MATERIALS AND METHODS: This was a retrospective study of adult patients with hyperuricemia and CKD (estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73m2) treated with febuxostat or allopurinol. The proportion of patients who achieved the treatment goal and the difference in efficacy between different drug doses were evaluated. Further, the effects on cardiovascular and renal functions were assessed. Cardiovascular risk is defined as cardiovascular events occurring after treatment initiation. RESULTS: We enrolled 316 patients in the study, with 83 and 233 patients in the allopurinol and febuxostat groups, respectively. The application of linear mixed model for analysis revealed that febuxostat 40 mg was more effective than allopurinol 100 mg in reducing the serum uric acid level. The results indicated that the long-term eGFR slope of the febuxostat group was positive, whereas that of the allopurinol group was negative. CONCLUSION: The results showed that, in patients with CKD and hyperuricemia, febuxostat can be used to reduce the serum uric acid level. The long-term use of febuxostat may exert a protective effect on the kidneys. Moreover, there were no obvious adverse reactions and the patients tolerated the drug well.


Assuntos
Alopurinol/uso terapêutico , Febuxostat/uso terapêutico , Supressores da Gota/uso terapêutico , Hiperuricemia/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Adulto , Alopurinol/efeitos adversos , Febuxostat/efeitos adversos , Supressores da Gota/efeitos adversos , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Ácido Úrico/sangue
4.
Wiad Lek ; 72(11 cz 1): 2082-2084, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31860850

RESUMO

OBJECTIVE: Introduction: Hyperuricemia is an independent risk factor for high-normal blood pressure (BP) both in men and women. The effect of uric acid (UA) on erythrocyte morphology in normotensive patients needs further study. The aim - to evaluate the impact of serum UA level on erythrocyte morphology in normotensive patients. PATIENTS AND METHODS: Materials and methods: Patients were divided into two group according to the UA level: the first group - 38 patients with UA level < 400 mcmol/L; the second group - 42 patients with UA level ≥ 400 mcmol/L. Studies on erythrocyte morphology were conducted using cytological analysis and scanning electron microscopy. RESULTS: Results: Patients of the 1st group had poikilocytosis level of 4,6%, while type I echinocytes were 3,2%, type II echinocytes - 1,1%, stomatocytes - 1,3%. In the 2nd group, poikilocytosis exceeding 5% was observed in 12 patients with mean values of altered shapes of 12,8±1,2%. In the 2nd group, type I echinocytes was 6,2% (9,4±0,9%) more, type II echinocytes - 1,3% (2,4±0,5%) more, stomatocytes - 0,3% (1,0±0,2%) more. In the study correlation between UA and poikilocytosis was found: in the 1st group - r = +0,21 and in the second group - r = +0,42. In the 1st group, correlation between UA and BP was moderate for SBP - r = +0,34 and weak for DBP - r = +0,29; in the 2nd group: SBP - r = +0,49 and r = +0,35 for DBP. CONCLUSION: Conclusions: Direct correlation between uric acid level and poikilocytosis level becomes more intensive when uric acid level exceeds ≥ 400 mcmol/L.


Assuntos
Eritrócitos , Pressão Sanguínea , Feminino , Humanos , Hipertensão , Hiperuricemia , Masculino , Ácido Úrico
5.
Medicine (Baltimore) ; 98(44): e17643, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689774

RESUMO

BACKGROUND: Current research has proved that psoriasis is associated with serum uric acid (SUAC) levels. Our purpose is to clarify SUAC levels and the incidence of hyperuricemia in psoriasis patients, and to compare SUCA levels in different groups' psoriasis patients. METHODS: We plan to search 7 electronic bibliographic databases (PubMed, Embase, Cochrane, and 4 Chinese databases) from inception to August 2019. Literatures selection and data collection will be performed independently by 2 authors. The Newcastle-Ottawa scale will be used to assess the methodologic quality and bias of included studies. Firstly, standard pairwise meta-analysis will be used to examine the considered data synthesis. Secondly, if the identified studies appear sufficiently similar within and across the different comparisons between different groups of psoriasis patients, we will estimate SUAC levels using network meta-analysis in different age and ethnicity psoriasis patients. Mean difference, risk ratio, and 95% confidence intervals will be used to assess the SUAC levels and the incidence of hyperuricemia in psoriasis patients. The software of Stata and WinBUGS will be used to calculations. RESULTS: The results will be published in a peer-reviewed journal. CONCLUSION: Our study will compare SUCA levels in different groups' psoriasis patients through network meta-analysis, and we believe our job is very meaningful. ETHICS AND DISSEMINATION: Our study is a secondary study of the existing literature. So, ethical and dissemination approval is not required.


Assuntos
Hiperuricemia/epidemiologia , Psoríase/epidemiologia , Ácido Úrico/sangue , Fatores Etários , Grupos Étnicos , Humanos , Hiperuricemia/sangue , Incidência , Meta-Análise em Rede , Estudos Observacionais como Assunto , Psoríase/sangue , Projetos de Pesquisa , Características de Residência , Fatores Sexuais
6.
Vasc Health Risk Manag ; 15: 291-299, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31616149

RESUMO

Background: A significant discovery was recently made in which participation in physical activity and sedentary behavior, two contrasting lifestyles, was found to be related to the frequency of hyperuricemia diagnosis. The purpose of this study was to identify the association between sedentary behavior and physical activity levels in South Korean men and women diagnosed with hyperuricemia. Methods: This study included 161,064 healthy men and women participants who had obtained a complete health examination. Physical activity levels and sitting time were assessed by the validated International Physical Activity Questionnaire Short Form Korean version. The presence of hyperuricemia in the subjects was determined by measuring serum uric acid (SUA) concentration (SUA ≥6 mg/dL [male], SUA ≥7 mg/dL [female]). Logistic regression analysis, adjusting other confounding factors, was conducted to identify the association of sedentary behavior and physical activity levels with hyperuricemia (p<0.05). Results: Subjects who spent ≥10 hr/day in sedentary behavior were more likely to have hyperuricemia than those who spent <5 hour/day in sedentary behavior (OR=1.08, 95% CI=1.03-1.12). The subject group that more frequently participated in health enhanced physical activity (HEPA) had a lower hyperuricemia odds ratio than the subject group with lower physical activity participation rate (OR=0.90, 95% Ci=0.86-0.93). From the analysis of sex (male, female), age (young, middle, older), methods of measuring obesity (body mass index, waist circumference, body fat percentage), the association of sedentary behavior and physical activity levels with hyperuricemia was shown differently in different multivariable models. Conclusion: Participation in regular physical activity and reduced sedentary time is highly recommended in order to reduce the prevalence of hyperuricemia.


Assuntos
Exercício , Estilo de Vida Saudável , Hiperuricemia/prevenção & controle , Comportamento Sedentário , Ácido Úrico/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Hiperuricemia/sangue , Hiperuricemia/diagnóstico , Hiperuricemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Proteção , República da Coreia/epidemiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Comportamento de Redução do Risco , Fatores de Tempo , Regulação para Cima , Adulto Jovem
7.
Medicine (Baltimore) ; 98(42): e17597, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626136

RESUMO

Hyperuricemia has received increasing attention as a major public health problem. This study aims to investigate the risk factors for hyperuricemia and to explore the relationship between changes in biochemical variables and incident hyperuricemia.A cross-sectional and subsequently prospective study was performed among adults who took their health checkups at Zhejiang University Hospital. The participants who were free of hyperuricemia at baseline received annual follow-up examinations during a 6-year period. Cox proportional hazards regression analyses were conducted to calculate the risks for incident hyperuricemia.Of the 9238 participants enrolled, 1704 (18.4%) were diagnosed as hyperuricemia. During 21,757 person-years of follow-up, 1492 incident hyperuricemia cases were identified. The incidence of hyperuricemia was 68.58 cases per 1000 person-year of follow-up in the overall participants. The prevalence and the incidence of hyperuricemia increased greatly in female older than 50 years. High levels of BMI, SBP, FPG, TG, LDL-C, ALT, BUN, and creatinine increased the risk of hyperuricemia. Suffering fatty liver also increased the risk of hyperuricemia. Subjects with increasing DBP, TG, BUN, creatinine, or decreasing HDL-C were more likely to incident hyperuricemia.This study revealed that the change of diastolic blood pressure (DBP), serum triglycerides (TG), blood urea nitrogen (BUN), creatinine, and high-density lipoprotein cholesterol (HDL-C) level were independently associated with incident hyperuricemia.


Assuntos
HDL-Colesterol/sangue , LDL-Colesterol/sangue , Creatinina/sangue , Hiperuricemia/etiologia , Triglicerídeos/sangue , Ácido Úrico/sangue , Adulto , Biomarcadores/sangue , Pressão Sanguínea/fisiologia , Nitrogênio da Ureia Sanguínea , Índice de Massa Corporal , China/epidemiologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Hiperuricemia/sangue , Hiperuricemia/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo
8.
Expert Opin Ther Pat ; 29(11): 871-879, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31593642

RESUMO

Introduction: Human urate transporter 1 (URAT1), which is an influx transporter protein, is located at the apical surface of renal tubular cells and presumed to be the major transporter responsible for the reabsorption of urate from blood. About 90% of patients develop hyperuricemia due to insufficient urate excretion; thus, it is important to develop URAT1 inhibitors that could enhance renal urate excretion by blocking the reabsorption of urate anion. Areas covered: In this review, the authors addressed the patent applications (2016-2019) about URAT1 inhibitors and some medicinal chemistry strategies employed in these patents. Expert opinion: Substituent decorating, bioisosterism, and scaffold hopping are three common medicinal chemistry strategies used in the discovery of URAT1 inhibitors. Meanwhile, the introduction of sulfonyl group into small molecules has become one of the important strategies for structural optimization of URAT1 inhibitors. Furthermore, developing drug candidates targeting both URAT1 and xanthine oxidase (XOD) has attracted lots of interest and attention.


Assuntos
Desenvolvimento de Medicamentos/métodos , Hiperuricemia/tratamento farmacológico , Transportadores de Ânions Orgânicos/antagonistas & inibidores , Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores , Animais , Humanos , Hiperuricemia/fisiopatologia , Patentes como Assunto , Ácido Úrico/metabolismo , Xantina Oxidase/antagonistas & inibidores
9.
Zhonghua Nei Ke Za Zhi ; 58(10): 745-750, 2019 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-31594172

RESUMO

With the improvement of people's living conditions and the prolonged lifespan, gout and hyperuricemia have increasingly become common chronic diseases in daily clinical practice for other physicians in addition to rheumatologists, even including general practitioners and primary care doctors. The European League Against Rheumatism (EULAR) firstly issued recommendations on gout diagnosis and management in 2006, which has been updated several times. Using a Delphi consensus approach, 2018 updated European League Against Rheumatism evidence-based recommendations for the diagnosis of gout finally formulated eight main recommendations, which was published online in June 2019. Not only does this edition emphasize the role of specialists, joint puncture or tophus aspirates and ultrasound in diagnosis, but also calls on all clinicians to pay more attention to risk factors of gout and associated comorbidities.


Assuntos
Medicina Baseada em Evidências , Gota/diagnóstico , Hiperuricemia/diagnóstico , Guias de Prática Clínica como Assunto/normas , Humanos , Fatores de Risco
11.
Rev Assoc Med Bras (1992) ; 65(9): 1155-1160, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618330

RESUMO

OBJECTIVE: In this study, we aimed to analyze the relationship between serum uric acid (UA) and microalbuminuria as a marker of renal injury in type 2 diabetes mellitus. METHODS: A total of 100 patients with type 2 diabetes mellitus were enrolled in the study. Participants were divided into two groups according to the urinary microalbumin/creatinine ratio: diabetic nephropathy and non-nephropathy group. UA and microalbuminuria were compared between the study groups. RESULTS: Serum UA levels of diabetic nephropathy patients were significantly higher than those in the non-nephropathy group (UA in patients with diabetic nephropathy groups: 6.3 (1.82) mg/dl, UA in patients of the non-nephropathic group: 4.85 (1.92) mg/dl) (p<0.001). There was a correlation between microalbuminuria and UA (r=0.238). This correlation was statistically significant (p=0.017). CONCLUSION: UA levels may be an important predictor of nephropathy in diabetic patients.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Hiperuricemia/complicações , Ácido Úrico/sangue , Idoso , Albuminúria/urina , Biomarcadores/sangue , Creatinina/urina , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade
13.
Int J Clin Pharmacol Ther ; 57(11): 567-570, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31496508

RESUMO

OBJECTIVE: Hyperuricemia is an independent risk factor for renal dysfunction, cardiovascular events, and gouty arthritis. Xanthine oxidoreductase (XOR) inhibitors inhibit uric acid (UA) production and may be treatment options for hyperuricemia patients. I aimed to evaluate the effects of topiroxostat on circulating lipid concentrations in patients with hyperuricemia. MATERIALS AND METHODS: 83 hyperuricemic patients taking topiroxostat were enrolled into this retrospective study. RESULTS: Serum UA significantly decreased, total cholesterol (TC) decreased, and low-density lipoprotein cholesterol (LDL-c) decreased between baseline and 24 weeks. CONCLUSION: Topiroxostat may have the potential to lower serum UA, TC, and LDL-c concentrations in hyperuricemic patients.


Assuntos
Hiperuricemia/sangue , Lipídeos/sangue , Nitrilos/uso terapêutico , Piridinas/uso terapêutico , Colesterol/sangue , LDL-Colesterol/sangue , Humanos , Hiperuricemia/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Ácido Úrico/sangue
14.
Molecules ; 24(18)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489932

RESUMO

Erding granule (EDG) is a traditional Chinese medicine that has recently been identified as having anti-hypouricemic effects. However, the active components and underlying mechanism for this new indication have not been elucidated. Therefore, we compared the effects of different EDG extracts (water, 50% ethanol and 95% ethanol) on serum uric acid concentrations in the hyperuricemia model mouse. We also analyzed the constituents of different extracts by ultra-high performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) to observe the variation between the active and inactive products. Extract activity and target site were evaluated by assessing uric acid- and inflammation-suppressing effects along with evaluating ability to regulate the uric acid transporter. The results showed that the 50% ethanol extract (EDG-50) had an obvious serum uric acid concentration lowering effect compared with water (EDG-S) and the 95% ethanol extract (EDG-95). UHPLC-Q-TOF-MS/MS analysis showed that EDG-50 was compositionally different to EDG-S and EDG-95. EDG-50 showed dose-dependent effects on reducing uric acid, suppressing inflammation and regulating uric acid transporters. Moreover, western blot analysis showed that EDG-50 down-regulated GLUT9 and URAT1 expression, and up-regulated OAT1 expression. Therefore, our findings enable the preliminarily conclusion that EDG-50 lowers serum uric acid concentrations, mainly by down-regulating the expression of GLUT9 and URAT1 proteins and up-regulating the expression of OAT1 proteins. This provides a research basis for clinical use of EDG as an anti-hyperuricemic agent.


Assuntos
Anti-Inflamatórios/administração & dosagem , Medicamentos de Ervas Chinesas/química , Etanol/administração & dosagem , Hiperuricemia/tratamento farmacológico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Etanol/química , Etanol/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Hiperuricemia/metabolismo , Masculino , Camundongos , Transportadores de Ânions Orgânicos/metabolismo , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas por Ionização por Electrospray , Ácido Úrico/sangue
15.
Cell Physiol Biochem ; 53(3): 508-517, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31502429

RESUMO

BACKGROUND/AIMS: Glucose transporter 9 (GLUT9/SLC2A9) is the major regulator of uric acid homeostasis in humans. Hyperuricemia due to impaired regulation by GLUT9 in pregnancy is closely associated with preeclampsia. While GLUT9 is expressed in two alternative splice variants, GLUT9a and GLUT9b, with different subcellular localizations, no functional differences of the two splice variants are known to date. The aim of this study was to investigate the function of both GLUT9 isoforms. METHODS: To characterize the different pharmacological properties of GLUT9a and GLUT9b electrophysiological studies of these isoforms and their modified variants, i.e. NmodGLUT9a and NmodGLUT9b, were performed using a Xenopus laevis oocytes model. Currents were measured by an electrode voltage clamp system. RESULTS: Functional experiments unveiled that uric acid transport mediated by GLUT9a but not GLUT9b is chloride-dependent: Replacing chloride by different anions resulted in a 3.43±0.63-fold increase of GLUT9a- but not GLUT9b-mediated currents. However, replacement by iodide resulted in a loss of current for GLUT9a but not GLUT9b. Iodide inhibits GLUT9a with an IC50 of 35.1±6.7µM. Modification of the N-terminal domain leads to a shift of the iodide IC50 to 1200±228µM. Using molecular docking studies, we identified two positively charged residues H23 and R31 in the N-terminal domain of hGLUT9a which can explain the observed functional differences. CONCLUSION: To the best of our knowledge, this is the first study showing that the N-terminal domain of hGLUT9a has a unique regulatory function and the potential to interact with small negatively charged ions like iodide. These findings may have significant implications in our understanding of hyperuricemia-associated diseases, specifically during pregnancy.


Assuntos
Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Pré-Eclâmpsia/sangue , Processamento Alternativo , Eletrofisiologia , Feminino , Humanos , Hiperuricemia/sangue , Hiperuricemia/metabolismo , Iodetos/metabolismo , Simulação de Acoplamento Molecular , Gravidez , Ácido Úrico/sangue
16.
Clin Lab ; 65(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414762

RESUMO

BACKGROUND: Hyperuricemia (HUA) is a metabolic disease caused by a disorder of purine metabolism, which increases the risk of cardio-cerebrovascular disease. Serum lipids and blood glucose are risk factors for metabolic syndrome. Thus, this study aimed to assess the prevalence of HUA and its relationship with serum lipids and blood glucose. METHODS: A total of 59,074 cases (32,623 males and 26,451 females) from three hospitals in Lanzhou city from January 2015 to December 2018 were grouped according to serum uric acid (SUA) level to analyze the differences in age, total cholesterol (TC), triacylglycerol (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), fasting blood glucose (FBG), creatinine (Cr), and blood urea nitrogen (BUN). The changes of prevalence of HUA among different age and gender groups was analyzed. Pearson's correlation analysis was used to analyze the correlation of SUA level with clinical indicators. The risk factors of HUA were analyzed by using binary logistic regression analysis. ROC curve was used to analyze the independent risk factors of elevated SUA. RESULTS: The overall prevalence rate of HUA was 19.87% and the prevalence rate of males was significantly higher than that of females (28.35% vs. 9.41%, χ2 = 3,289.143, p < 0.01). The prevalence rates of HUA from 2015 - 2018 were 19.54%, 19.31%, 18.64%, and 21.81%, respectively. Compared with the normal SUA group, TC, TG, and LDL significantly increased in the HUA group. The correlation analysis showed that SUA was negatively correlated with gender and HDL, and positively correlated with age, FBG, TC, TG, and LDL. The logistic regression analysis revealed that TG, TC, and LDL were risk factors for HUA. The ROC curve analysis showed that the risk of HUA significantly increased when TG was above 1.645 mmol/L. CONCLUSIONS: The overall prevalence of HUA in physical examination population has generally been at a high level in the past 4 years. Serum lipids and blood glucose may be independent risk factors for predicting HUA.


Assuntos
Biomarcadores/sangue , Glicemia/metabolismo , Hiperuricemia/sangue , Lipídeos/sangue , Exame Físico/estatística & dados numéricos , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos
17.
Horm Metab Res ; 51(8): 522-530, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31408898

RESUMO

The risk of thyroid autoimmunity and thyroid dysfunction among patients with gout and hyperuricemia has not been well defined. This study was undertaken to examine the impact of gout and hyperuricemia on risk of thyroid disorders including thyroid autoimmunity and thyroid dysfunction. A population-based cross-sectional study was conducted to assess the risk of thyroid autoimmunity and thyroid dysfunction related to gout and hyperuricemia, which included 115 gout patients, 439 hyperuricemic patients, and 2 254 individuals without gout and hyperuricemia. A systematic review and meta-analysis of 14 observational studies was also done to systematically evaluate the risk of thyroid dysfunction among patients with gout and hyperuricemia. Findings from the cross-sectional study suggested a significantly increased risk of hypothyroidism among female gout patients (OR=2.44, 95% CI 1.15-5.17, p=0.02). Besides, gout could also substantially increase risk of Hashimoto's thyroiditis in women (OR=3.15, 95% CI 1.53-6.49, p=0.002). The meta-analysis proved a considerably increased risk of hypothyroidism among both gout patients (OR=1.51, 95% CI 1.23-1.85, p<0.001) and hyperuricemic patients (OR=1.34, 95% CI 1.11-1.61, p=0.002). Moreover, this meta-analysis also suggested that gout could also significantly increase the risk of hyperthyroidism (OR=1.25, 95% CI 1.06-1.48, p=0.01). The findings from the study suggest increasing risk of hypothyroidism and Hashimoto's thyroiditis among gout patients. Moreover, gout but not hyperuricemia is linked to increased risk of hyperthyroidism. More studies are warranted to elucidate the influence of gout and hyperuricemia on thyroid disorders.


Assuntos
Gota/complicações , Hiperuricemia/complicações , Doenças da Glândula Tireoide/etiologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Metanálise como Assunto , Estudos Observacionais como Assunto , Prognóstico , Fatores de Risco , Revisão Sistemática como Assunto
18.
Eur J Med Chem ; 181: 111559, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31376568

RESUMO

Xanthine oxidase is an important target for the treatment of hyperuricemia, gout and other related diseases. Analysis of the high-resolution structure of xanthine oxidase with febuxostat identified the existence of a subpocket formed by the residues Leu648, Asn768, Lys771, Leu1014 and Pro1076. In this study, we designed and synthesized a series of 2-[4-alkoxy-3-(1H-tetrazol-1-yl) phenyl]-6-oxo-1,6-dihydropyrimidine-5-carboxylic acid derivatives (8a-8z) with a tetrazole group targeting this subpocket of the xanthine oxidase active site, and they were further evaluated for their inhibitory potency against xanthine oxidase in vitro. The results showed that all the tested compounds (8a-8z) exhibited an apparent xanthine oxidase inhibitory potency, with IC50 values ranging from 0.0288 µM to 0.629 µM. Among them, compound 8u emerged as the most potent xanthine oxidase inhibitor, with an IC50 value of 0.0288 µM, which was comparable to febuxostat (IC50 = 0.0236 µM). The structure-activity relationship results revealed that the hydrophobic group at the 4'-position was indispensable for the inhibitory potency in vitro against xanthine oxidase. A Lineweaver-Burk plot revealed that the representative compound 8u acted as a mixed-type inhibitor for xanthine oxidase. Furthermore, molecular modeling studies were performed to gain insights into the binding mode of 8u with xanthine oxidase and suggested that the tetrazole group of the phenyl unit was accommodated in the subpocket, as expected. Moreover, a potassium oxonate-induced hyperuricemia model in rats was chosen to further confirm the hypouricemic effect of compound 8u, and the result demonstrated that compound 8u could effectively reduce serum uric acid levels at an oral dose of 5 mg/kg. In addition, acute oral toxicity study in mice indicated that compound 8u was nontoxic and tolerated at a dose up to 2000 mg/kg. Thus, compound 8u could be a potential and efficacious agent in treatment of hyperuricemia with low toxicity.


Assuntos
Ácidos Carboxílicos/farmacologia , Desenho de Drogas , Inibidores Enzimáticos/farmacologia , Pirimidinas/farmacologia , Xantina Oxidase/antagonistas & inibidores , Animais , Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/química , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Feminino , Hiperuricemia/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos , Estrutura Molecular , Pirimidinas/síntese química , Pirimidinas/química , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Xantina Oxidase/metabolismo
19.
Nutrients ; 11(8)2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31387233

RESUMO

In previous studies, the elevated dietary inflammatory index (DII®) scores have been consistently associated with several chronic diseases. However, the relationship with hyperuricemia remains unknown. The aim of this study was to determine if the DII is associated with hyperuricemia risk. The study included 13,701 participants (men 5102; women 8599) in a large-scale cross-sectional study in South Korea. A validated semi-quantitative food frequency questionnaire (SQFFQ) was used to measure dietary intake, and blood samples were obtained to determine hyperuricemia. As the DII score increased, the hyperuricemia risk increased among women (OR 1.35, 95% CI 1.03-1.77, p trend = 0.02). However, no significant results were found for men. Women with lower BMI scores had higher risks of hyperuricemia with higher DII scores (OR 1.62, 95% CI 1.05-2.52, p trend = 0.03). As the DII increased, however, only women who consumed alcohol ("past or current drinkers") had higher risks of hyperuricemia (OR 1.92, 1.22-3.02, p trend = 0.004). Among the DII components, intake of flavonoids showed a significant association with the hyperuricemia risk in women (OR 0.75, 0.59-0.96, p trend = 0.03). Our results suggest that higher intake of pro-inflammatory diet is significantly associated with higher risk of hyperuricemia among women. These results reinforce the importance of less pro-inflammatory habitual dietary patterns in lowering the risk of hyperuricemia and secondary afflictions such as cardiovascular diseases.


Assuntos
Dieta/efeitos adversos , Hiperuricemia/epidemiologia , Inflamação/epidemiologia , Ácido Úrico/sangue , Idoso , Biomarcadores , Estudos de Casos e Controles , Estudos Transversais , Comportamento Alimentar , Feminino , Humanos , Hiperuricemia/sangue , Hiperuricemia/diagnóstico , Inflamação/sangue , Inflamação/diagnóstico , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Prognóstico , República da Coreia/epidemiologia , Medição de Risco , Fatores de Risco , Fatores Sexuais
20.
Pan Afr Med J ; 32: 165, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303934

RESUMO

Introduction: Very few studies have been conducted to evaluate the prevalence of hyperuricemia and its impact on the prognosis amongst acute hemorrhagic stroke (AHS) patients. The objectives was to determine the prevalence of hyperuricemia in AHS patients and examined the association between hyperuricemia and stroke outcomes in the Douala General Hospital (DGH). Methods: This was a hospital based prospective cohort which included AHS patients with baseline SUA levels and 3 months post stroke follow-up data. SUA values were divided into quintiles. Associations between hyperuricemia and stroke outcomes were analyzed using multiple logistic regression and survival analysis (cox regression and Kaplan Meier). Results: A total of 221 AHS patients were reviewed with a mean age of 55.8±11.8 years. The prevalence of hyperuricemia among AHS patients was 34.4% with mean SUA level of 376.8±131.9 µmol/l. On multivariate analysis, hyperuricemia was not independently associated with early death [(OR = 1.072 (CI: 0.370-3.056; p = 0.897)] and poor functional outcome [(OR=2.487 (CI: 0.771-8.699; p = 0.154)] after hemorrhagic stroke. No significant increase in stroke deaths was observed across higher SUA quintiles amongst hemorrhagic stroke patients (p = 0.326). No statistically significant correlation was observed between SUA level and NIHSS (r = 0.063, p = 0.353) and between SUA level and mRS (r = 0.030, p = 0.662) in hemorrhagic stroke. Conclusion: About one third of patients present with hyperuricemia in the acute phase of hemorrhagic stroke. Hyperuricemia can act as risk factor for stroke because of its relationship with CVRFs but hyperuricemia has no impact on the severity and short-term outcome amongst black African hemorrhagic stroke patients.


Assuntos
Hiperuricemia/epidemiologia , Hemorragias Intracranianas/sangue , Acidente Vascular Cerebral/sangue , Ácido Úrico/sangue , Adulto , Grupo com Ancestrais do Continente Africano , Idoso , Camarões , Estudos de Coortes , Feminino , Seguimentos , Hospitais Gerais , Humanos , Hemorragias Intracranianas/mortalidade , Hemorragias Intracranianas/patologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Prognóstico , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/patologia , Análise de Sobrevida
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