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1.
J Assoc Physicians India ; 68(2): 31-34, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32009359

RESUMO

Background: Coronary artery disease (CAD) is the leading cause of mortality and morbidity in present days. Recent epidemiological and clinical evidences suggest that serum uric acid can be one of the useful markers in assessing the risk of mortality in acute myocardial infarction. Objective: To find out the association in serum uric acid level and Killip classes and ejection fraction. Methodology: It was an observational prospective study. 100 patients of acute myocardial infarction were enrolled and physical examination with special reference to Killip classification, ECG, 2D- Echocardiogram, Serum uric acid and all routine investigations were carried out on 0, 3rd and 7th day. Serum uric acid and Killip class and ejection fractions on day 0, day 3 and day 7 were compared. Results: In this present study majority of the patients were in the age group of >50 years (68%). There was statistically significant increase in uric acid levels with increasing Killip class on day 0, day 3 and day 7. Mean serum uric acid level was 4.4 mg/dl in Killip class I, 7.01 mg/dl in class II, 8.29 mg/dl in class III, and 9.87 mg/ dl in class IV on day 0; 4.46 mg/dl in Killip class I, 7.09 mg/dl in class II, 8.53 mg/ dl in class III, and 9.43 mg/dl in class IV on day 3; 4.72 mg/dl in Killip class I, 6.62 mg/dl in class II, on day 7. There was statistically significant negative correlation (p-value 0.0009, 0.001, 0.0326 at day 0, 3 & 7) between serum uric acid levels and ejection fraction at all the three occasions i.e. day 0, day 3 and day 7. Conclusion: The present study concludes that serum uric acid level have significant association with Killip class, left ventricular failure and mortality i.e. higher the serum uric acid, higher the Killip class, more severe left ventricular dysfunction and higher the mortality.The present study concludes that serum uric acid level have significant association with Killip class, left ventricular failure and mortality i.e. higher the serum uric acid, higher the Killip class, more severe left ventricular dysfunction and higher the mortality.


Assuntos
Infarto do Miocárdio/diagnóstico , Ácido Úrico/sangue , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Disfunção Ventricular Esquerda
2.
J Zoo Wildl Med ; 50(4): 927-936, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926525

RESUMO

Seabirds have been widely used for monitoring the health of the oceans in diverse marine regions. Among low-cost survey strategies, systematic surveys of seabirds beached on coasts have been developed since the 20th century. However, these studies do not always address blood aspects. The assessment of the health status of birds based on the analysis of hematological and plasma chemistry is crucial to evaluate the overall health status profile of live organisms. Here, the authors study the variability of blood parameters by sex, age class, and year of beached Magellanic Penguin during the nonreproductive period in northern Argentina. Of 44 penguins, 77% were categorized as younger juveniles and the rest as older juveniles, and were captured and studied in coastal areas of Buenos Aires Province during the summers of 2017 and 2018. The mean body weight of beached penguins was affected by the age class of the individuals; most of the younger juveniles showed poor condition in terms of body mass (1,761 ± 235 g). No significant differences were observed in body weight between years and sex. Still, there were significant differences between years for alkaline phosphatase (ALP) and creatine phosphokinase (CPK) values. Twelve of the 20 blood parameters analyzed differ significantly with the age class of the beached penguins; younger juveniles were in a state of inanition. Our results may serve as a necessary first step in improving the conservation status of the Magellanic Penguin in nonbreeding grounds of Argentina, and call for a better knowledge of the health status of the species along its annual cycle.


Assuntos
Contagem de Eritrócitos/veterinária , Hematócrito , Contagem de Leucócitos/veterinária , Estações do Ano , Spheniscidae/sangue , Envelhecimento , Fosfatase Alcalina/sangue , Animais , Animais Selvagens , Anticorpos Heterófilos , Argentina , Glicemia , Proteínas Sanguíneas , Colesterol/sangue , Creatina Quinase/sangue , Feminino , Hemoglobinas , Contagem de Linfócitos/veterinária , Masculino , Fósforo/sangue , Transaminases/sangue , Ureia/sangue , Ácido Úrico/sangue
3.
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
4.
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
5.
Chemosphere ; 238: 124603, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31442773

RESUMO

Environmental pollution is a risk factor for kidney dysfunction. However, the combined toxicity of air pollutants on kidney function is scarce. We estimated the relationship between combined toxicity of air pollutants and kidney function among adult women (n = 7071, 18-65 years old) in Mianyang City, Southwest China. We measured serum concentrations of uric acid, urea, creatinine, and cystatin C, and we calculated the individual estimated glomerular filtration rate (eGFR) using a cystatin C-based equation developed specifically for Chinese patients with CKD equation. Air pollution data were collected to calculate the individual average daily dose (ADD) of pollutants based on the air quality complex index (AQCI). Mean AQCI was higher in winter and lower in summer, and followed the monthly and seasonal trends of air pollutants. Concomitantly, individual ADD was also higher in winter and lower in summer, and the seasonal differences were reflected in the levels of kidney biomarkers (including uric acid, urea, creatinine, cystatin C, and eGFR). With an interquartile range (IQR: 1.04-1.50 m3/day/kg) increases of ADD, the serum concentrations of uric acid, urea, creatinine, and cystatin C increase [B (95%CI): 1.774 (0.318, 3.231) umol/L, 0.218 (0.1888, 0.247) mmol/L, 1.501 (1.016, 1.986) umol/L, and 0.006 (0.003, 0.009) mg/L, respectively], whereas eGFR decreases [B (95%CI): -0.776 (-1.106, -0.446) mL/min/1.73 m2]. Totally, the relationship between combined toxicity of air pollutants and kidney function in Chinese adult women suggests that the toxicity of combined air pollutants inversely affects kidney function, which might accelerate the risk of CKD.


Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar/análise , Exposição Ambiental/efeitos adversos , Taxa de Filtração Glomerular/fisiologia , Adolescente , Adulto , Idoso , Algoritmos , Biomarcadores/sangue , China , Creatinina/sangue , Cistatina C/sangue , Feminino , Humanos , Rim/patologia , Pessoa de Meia-Idade , Fatores de Risco , Ureia/sangue , Ácido Úrico/sangue , Adulto Jovem
6.
Chem Commun (Camb) ; 55(92): 13880-13883, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31675031

RESUMO

Based on the unique property of preferential sequestration of guest molecules, coacervate microdroplets are proposed as enzyme active membrane-free protocells, in which uricase is loaded for efficient detoxification of uric acid in serum.


Assuntos
Urato Oxidase/metabolismo , Ácido Úrico/metabolismo , Células Artificiais/química , Dextranos/química , Corantes Fluorescentes/química , Humanos , Polietilenos/química , Estabilidade Proteica , Compostos de Amônio Quaternário/química , Solubilidade , Ácido Úrico/sangue
7.
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
8.
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
9.
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
10.
Zhonghua Nei Ke Za Zhi ; 58(10): 751-757, 2019 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-31594173

RESUMO

Objective: To investigate the characteristics of body composition (BC) in gout patients and its clinical significance. Methods: Consecutive gout patients were recruited between August 2017 and December 2018. Demographic information, clinical characteristics and comorbidities were collected. BC was assessed by bioelectric impedance analysis including body fat percentage (BF%), trunk and limb BF%, appendicular skeletal muscle index. Overfat was defined by BF% ≥25% for male and ≥35% for female. The association between BC and serum uric acid (sUA) was evaluated by multiple linear regression. Results: A total of 362 gout patients were recruited with median age 38 (30, 52) years, 96.1% (348/362) were male. Mean sUA was (551±133) µmol/L. The mean BF% was (25.8±6.4)% with 53.6%(194/362) patients overfat. Male gout patients with overfat showed more affected joints [4(2, 6) vs. 2(2, 5)], higher sUA [(576±126)µmol/L vs. (523±134) µmol/L], higher prevalence of dyslipidemia [70.1%(131/187) vs. 54.0%(87/161)], metabolic syndrome [60.8%(118/187) vs. 28.0%(47/161)], fatty liver [58.2%(113/187) vs. 35.1%(59/161)] and hypertension [44.4%(83/187) vs. 25.5%(41/161)] than male patients with normal fat (all P<0.05). Their BF%, trunk BF% and limb BF% were positively correlated with the numbers of affected joints, sUA, metabolic syndrome, fatty liver, and hypertension, respectively (r=0.154-0.435, all P<0.05). Multivariable linear regression suggested that BF% (ß=4.29, P=0.020) and trunk BF% (ß=9.11, P=0.007), but not limb BF%, were positively correlated with sUA. Conclusion: Overfat is very common in gout patients. The proportion of trunk fat in male patients is positively correlated with sUA. When assessing obesity in gout patients clinically, body composition analysis should be performed simultaneously.


Assuntos
Composição Corporal/fisiologia , Gota/diagnóstico , Obesidade/epidemiologia , Ácido Úrico/sangue , Adulto , Dislipidemias/epidemiologia , Feminino , Gota/sangue , Gota/epidemiologia , Humanos , Hipertensão/sangue , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade/sangue , Prevalência
11.
Int J Clin Pharmacol Ther ; 57(12): 590-595, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31587751

RESUMO

OBJECTIVES: This aim of this study is to investigate the regulation of serum uric acid (SUA) levels with canagliflozin in relation to diabetic parameters. MATERIALS AND METHODS: Drug-naïve subjects with type 2 diabetes (T2DM) received 50 - 100 mg/day canagliflozin monotherapy (n = 40) for 3 months. Levels of SUA and some diabetic parameters were monitored. RESULTS: In the overall subjects, significant negative correlations were observed between the changes (Δ) of SUA and the baseline SUA levels (R = -0.392, p < 0.02). The subjects were divided into two subgroups (n = 20 each) according to the changes of SUA levels (above the median (group A): from 4.79 ± 1.22 to 5.34 ± 1.39 mg/dL; and below the median (group B): from 5.80 ± 1.08 to 4.98 ± 0.97 mg/dL). Significant increases of SUA levels were observed in group A (11.4%, p < 0.0002), while significant decreases of SUA levels were seen in group B (-14.1%, p < 0.00001). Significant correlations were seen between the baseline levels of SUA and those of homeostasis model assessment (HOMA)-B (R = 0.463, p < 0.04) and between the changes of SUA and those of HOMA-B (R = 0.420, p < 0.05) only in group A. Higher degrees of elevations of HOMA-B and decreases of HbA1c/fasting blood glucose (FBG) were seen in group A versus group B. CONCLUSION: These results suggest that 1) high SUA levels decreased while low SUA levels increased with canagliflozin; 2) better glycemic efficacies and higher degrees of enhancement of ß-cell function were observed in those with elevated SUA levels with canagliflozin; 3) SUA might be linked to modulation of ß-cell function.


Assuntos
Canagliflozina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Células Secretoras de Insulina/fisiologia , Ácido Úrico/sangue , Glicemia , Humanos
12.
Nat Genet ; 51(10): 1459-1474, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31578528

RESUMO

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.


Assuntos
Doenças Cardiovasculares/sangue , Marcadores Genéticos , Gota/sangue , Doenças Metabólicas/sangue , Polimorfismo de Nucleotídeo Único , Transdução de Sinais , Ácido Úrico/sangue , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Estudos de Coortes , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Gota/epidemiologia , Gota/genética , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 4 Nuclear de Hepatócito/genética , Humanos , Rim/metabolismo , Rim/patologia , Fígado/metabolismo , Fígado/patologia , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/genética , Proteínas de Neoplasias/genética , Especificidade de Órgãos
13.
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
14.
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
15.
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
16.
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
17.
Neurology ; 93(14): e1328-e1338, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31484712

RESUMO

OBJECTIVE: To investigate whether women and men with Parkinson disease (PD) differ in their biochemical and clinical responses to long-term treatment with inosine. METHODS: The Safety of Urate Elevation in Parkinson's Disease (SURE-PD) trial enrolled 75 people with early PD and baseline serum urate below 6 mg/dL and randomized them to 3 double-blinded treatment arms: oral placebo or inosine titrated to produce mild (6.1-7.0 mg/dL) or moderate (7.1-8.0 mg/dL) serum urate elevation for up to 2 years. Parkinsonism, serum urate, and plasma antioxidant capacity were measured at baseline and repeatedly on treatment; CSF urate was assessed once, at 3 months. Here in secondary analyses results are stratified by sex. RESULTS: Inosine produced an absolute increase in average serum urate from baseline that was 50% greater in women (3.0 mg/dL) than in men (2.0 mg/dL), consistent with expected lower baseline levels in women. Similarly, only among women was CSF urate significantly greater on mild or moderate inosine (+87% [p < 0.001] and +98% [p < 0.001], respectively) than on placebo (in contrast to men: +10% [p = 0.6] and +14% [p = 0.4], respectively). Women in the higher inosine dosing group showed a 7.0 Unified Parkinson's Disease Rating Scale (UPDRS) points/year lower rate of decline vs placebo (p = 0.01). In women, slower rates of UPDRS change were associated with greater increases in serum urate (r = -0.52; p = 0.001), and with greater increases in plasma antioxidant capacity (r = -0.44; p = 0.006). No significant associations were observed in men. CONCLUSIONS: Inosine produced greater increases in serum and CSF urate in women compared to men in the SURE-PD trial, consistent with the study's design and with preliminary evidence for slower clinical decline in early PD among women treated with urate-elevating doses of inosine. CLINICALTRIALSGOV IDENTIFIER: NCT00833690. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that inosine produced greater urate elevation in women than men and may slow PD progression in women.


Assuntos
Doença de Parkinson/sangue , Doença de Parkinson/diagnóstico , Caracteres Sexuais , Ácido Úrico/sangue , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Inosina/uso terapêutico , Masculino , Testes de Estado Mental e Demência , Doença de Parkinson/tratamento farmacológico , Resultado do Tratamento
18.
Nat Commun ; 10(1): 3672, 2019 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-31413315

RESUMO

Besides genome editing, CRISPR-Cas12a has recently been used for DNA detection applications with attomolar sensitivity but, to our knowledge, it has not been used for the detection of small molecules. Bacterial allosteric transcription factors (aTFs) have evolved to sense and respond sensitively to a variety of small molecules to benefit bacterial survival. By combining the single-stranded DNA cleavage ability of CRISPR-Cas12a and the competitive binding activities of aTFs for small molecules and double-stranded DNA, here we develop a simple, supersensitive, fast and high-throughput platform for the detection of small molecules, designated CaT-SMelor (CRISPR-Cas12a- and aTF-mediated small molecule detector). CaT-SMelor is successfully evaluated by detecting nanomolar levels of various small molecules, including uric acid and p-hydroxybenzoic acid among their structurally similar analogues. We also demonstrate that our CaT-SMelor directly measured the uric acid concentration in clinical human blood samples, indicating a great potential of CaT-SMelor in the detection of small molecules.


Assuntos
Proteínas Associadas a CRISPR , Sistemas CRISPR-Cas , Endodesoxirribonucleases , Fatores de Transcrição , Regulação Alostérica , Bioensaio , Clostridiales , Humanos , Limite de Detecção , Motivos de Nucleotídeos , Parabenos , Biologia Sintética , Ácido Úrico/sangue
19.
Hypertension ; 74(4): 991-997, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31446801

RESUMO

Preeclampsia is characterized by an imbalance in angiogenic factors, including sEng (soluble endoglin). However, the relationship of sEng with the severity of preeclampsia, clinical, and laboratory parameters, and the occurrence of adverse outcomes are not fully elucidated. We studied 1002 women with preeclampsia. Serum concentrations of sEng were measured by ELISA. Serum sEng levels were significantly different (P<0.001) in patients with preeclampsia than in healthy pregnancy. In addition, these factors were markedly different in patients with hemolysis, elevated liver enzymes, low platelet count syndrome and eclampsia than in patients with preeclampsia with or without severe features (P<0.001) and in patients with preeclampsia with severe features than in those without severe features (P<0.001). sEng correlated positively with blood pressure, proteinuria, and levels of creatinine, uric acid, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase; and inversely with gestational age, infant's birth weight, and platelets counts (P<0.001 for all). The risk of combined and specific adverse outcomes (pulmonary edema, acute renal failure, placental abruption, hepatic hematoma or rupture, maternal death, cerebral hemorrhage, thrombocytopenia, elevated liver enzymes, preterm delivery, small for gestational age infant, and need for endotracheal intubation, positive inotropic drug support, and hemodialysis) was higher in patients with sEng values in the highest quartile (odds ratio ≥3.1) compared with the lowest quartile. Patients in the highest quartile of sEng were more likely to deliver early compared with those in the lowest quartile (HR, 2.33; 95% CI, 1.91-2.84). We concluded that circulating concentrations of sEng seem to be a suitable marker to assess the severity of preeclampsia and are associated with increased risk of adverse outcomes.


Assuntos
Endoglina/sangue , Pré-Eclâmpsia/diagnóstico , Adulto , Biomarcadores/sangue , Peso ao Nascer/fisiologia , Pressão Sanguínea/fisiologia , Creatinina/sangue , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Pré-Eclâmpsia/sangue , Gravidez , Resultado da Gravidez , Índice de Gravidade de Doença , Ácido Úrico/sangue
20.
J Clin Neurosci ; 69: 155-159, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31420274

RESUMO

Sleep disturbance is a common psychiatric complication after stroke. Oxidative stress has been an important pathophysiological mechanism of sleep disturbance. However, no study has explored the relationship between uric acid (UA) and post-stroke sleep quality. This prospective study included 191 patients who were followed up for two months after acute ischemic stroke. Serum UA levels were measured at admission and divided into 3 tertiles (≤251 µmol/L, 252-326 µmol/L, ≥327 µmol/L). Patients in the 3rd tertile of UA levels had a lower incidence of poor sleep quality than those belonging to 2nd or 1st tertile, respectively (9.7% vs. 27.7% vs. 35.9%; P = 0.002). Furthermore, high UA levels (≥327 µmol/L) were independently associated with low risk of poor sleep quality (OR = 0.129, 95%CI = 0.031-0.528, P = 0.004) after adjusting for demographics, cardiovascular risk factors, stroke severity, functional outcome and depressive symptoms. High modified Rankin Scale score and depressive symptoms were associated with increased risk of poor sleep quality after stroke (OR = 1.836, 95%CI = 1.035-3.354, P = 0.038) and (OR = 5.082, 95%CI = 1.709-15.115, P = 0.003). In conclusion, high UA levels may reduce the risk of poor sleep quality after acute ischemic stroke. Further randomized controlled trials are necessary in examining whether appropriate UA supplement could provide a potential prevention or therapeutic target for sleep disturbance after stroke.


Assuntos
Transtornos do Sono-Vigília/sangue , Transtornos do Sono-Vigília/etiologia , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/complicações , Ácido Úrico/sangue , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
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