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2.
Gut Microbes ; 16(1): 2399213, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39288233

RESUMO

Hyperuricemia, a prevalent metabolic disorder, poses a susceptibility to various complications. The conventional pharmacotherapeutic approaches for hyperuricemia often entail notable adverse effects, posing substantial clinical challenges. Hence, the imperative lies in the development of novel, safe and effective strategies for preventing and treating hyperuricemia. Here, we developed a probiotic Escherichia coli Nissle 1917 strain, designated as YES301, which contains a rationally designed xanthine importer XanQ, enabling efficient uptake of xanthine and hypoxanthine, consequently leading to reduced serum uric acid concentrations and amelioration of renal impairments in a murine model of hyperuricemia. Importantly, YES301 exhibited a therapeutic efficacy comparable to allopurinol, a conventional uric acid-lowering agent, and manifesting fewer adverse effects and enhanced biosafety. These findings highlight the promising potential of engineered probiotics in the management of hyperuricemia through reducing intestinal purine levels.


Assuntos
Escherichia coli , Hiperuricemia , Probióticos , Xantina , Hiperuricemia/tratamento farmacológico , Hiperuricemia/terapia , Hiperuricemia/metabolismo , Probióticos/administração & dosagem , Probióticos/uso terapêutico , Animais , Camundongos , Xantina/metabolismo , Escherichia coli/metabolismo , Escherichia coli/genética , Ácido Úrico/metabolismo , Ácido Úrico/sangue , Modelos Animais de Doenças , Masculino , Humanos , Camundongos Endogâmicos C57BL , Hipoxantina/metabolismo , Alopurinol/uso terapêutico
3.
Nat Rev Dis Primers ; 10(1): 58, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39174582

RESUMO

Tumour lysis syndrome (TLS) represents a critical oncological emergency characterized by extensive tumour cell breakdown, leading to the swift release of intracellular contents into the systemic circulation, outpacing homeostatic mechanisms. This process results in hyperuricaemia (a by-product of intracellular DNA release), hyperkalaemia, hyperphosphataemia, hypocalcaemia and the accumulation of xanthine. These electrolyte and metabolic imbalances pose a significant risk of acute kidney injury, cardiac arrhythmias, seizures, multiorgan failure and, rarely, death. While TLS can occur spontaneously, it usually arises shortly after the initiation of effective treatment, particularly in patients with a large cancer cell mass (defined as ≥500 g or ≥300 g/m2 of body surface area in children). To prevent TLS, close monitoring and hydration to improve renal perfusion and urine output and to minimize uric acid or calcium phosphate precipitation in renal tubules are essential. Intervention is based on the risk of a patient of having TLS and can include rasburicase and allopurinol. Xanthine, typically enzymatically converted to uric acid, can accumulate when xanthine oxidases, such as allopurinol, are administered during TLS management. Whether measurement of xanthine is clinically useful to optimize the use of allopurinol or rasburicase remains to be determined.


Assuntos
Alopurinol , Síndrome de Lise Tumoral , Síndrome de Lise Tumoral/fisiopatologia , Síndrome de Lise Tumoral/etiologia , Síndrome de Lise Tumoral/diagnóstico , Síndrome de Lise Tumoral/complicações , Humanos , Alopurinol/uso terapêutico , Hiperuricemia/fisiopatologia , Hiperuricemia/complicações , Urato Oxidase/uso terapêutico , Hiperpotassemia/fisiopatologia , Hiperpotassemia/etiologia , Hiperpotassemia/terapia , Ácido Úrico , Xantina , Neoplasias/fisiopatologia , Neoplasias/complicações
4.
Ann Med ; 56(1): 2396075, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39183708

RESUMO

Hyperuricaemia (HUA) is an abnormally high concentration of serum urate caused by either an excess of uric acid production or decreased excretion capacity in the body. Serum urate concentration forms sodium salts that deposit in the soft tissues of the joints, ultimately leading to gout. Additionally, HUA is strongly associated with several acute and chronic illnesses. In various clinical guidelines and practices, xanthine oxidase inhibitors, such as allopurinol and febuxostat, are commonly used as the initial medication for treating HUA. However, extended usage of urate-lowering drugs may have risks, including cardiovascular thrombotic events and hepatic impairment. Implementing a scientifically informed fitness diet in conjunction with appropriate exercise may decrease HUA. Unfortunately, there is currently a shortfall in exercise intervention trials for individuals suffering from HUA. Most of the previous evidence suggesting that exercise improves serum urate levels comes from intervention trials in other populations, and serum urate is only one of the outcomes observed. This opinion article analyses the causes of HUA, offers dietary and exercise guidance with the aim of furnishing a point of reference for individuals with HUA or fitness enthusiasts.


Assuntos
Terapia por Exercício , Exercício Físico , Gota , Hiperuricemia , Ácido Úrico , Humanos , Alopurinol/efeitos adversos , Alopurinol/uso terapêutico , Exercício Físico/fisiologia , Terapia por Exercício/métodos , Febuxostat/efeitos adversos , Febuxostat/uso terapêutico , Gota/sangue , Gota/etiologia , Gota/terapia , Supressores da Gota/efeitos adversos , Supressores da Gota/uso terapêutico , Hiperuricemia/sangue , Hiperuricemia/complicações , Hiperuricemia/terapia , Ácido Úrico/sangue , Ácido Úrico/metabolismo
5.
Arq Bras Cardiol ; 121(8): e20230659, 2024 Jul.
Artigo em Português, Inglês | MEDLINE | ID: mdl-39194039

RESUMO

BACKGROUND: Recently, it was demonstrated that allopurinol, a xanthine oxidase inhibitor, has cardiovascular and anti-ischaemic properties and may be a metabolic antianginal agent option.Objective: The objective of this study was to evaluate the antianginal effect of allopurinol as a third drug for patients with stable coronary artery disease (CAD). METHODS: This was a randomized clinical trial between 2018 and 2020 including patients with CAD who maintained angina despite initial optimization with beta-blockers and calcium channel blockers. The individuals were randomized 1:1 to 300 mg of allopurinol twice daily or 35 mg of trimetazidine twice daily. The main outcome was the difference in the angina frequency domain of the Seattle Angina Questionnaire (SAQ-AF). A probability (p) value < 0.05 was considered statistically significant. RESULTS: A hundred and eight patients were included in the randomization phase, with 54 (50%) in the allopurinol group and 54 (50%) in the trimetazidine group. Six (5.6%) individuals, 3 from each group, were lost to follow-up for the primary outcome. In the allopurinol and trimetazidine groups, the median SAQ-AF scores were 50 (30.0 to 70.0) and 50 (21.3 to 78.3), respectively. In both groups, the SAQ-AF score improved, but the median of the difference compared to baseline was lower in the allopurinol group (10 [0 to 30] versus 20 [10 to 40]; p < 0.001), as was the mean of the difference in the total SAQ score (12.8 ± 17.8 versus 21.2 ± 15.9; p = 0.014). CONCLUSION: Both allopurinol and trimetazidine improved the control of angina symptoms; however, trimetazidine presented a greater gain compared to baseline. Brazilian Registry of Clinical Trials - Registration Number RBR-5kh98y.


FUNDAMENTO: Recentemente, foi demonstrado que o alopurinol, um inibidor da xantina oxidase, possui propriedades cardiovasculares e anti-isquêmicas e pode ser uma opção de agente antianginoso metabólico. OBJETIVO: O objetivo do presente estudo foi avaliar o efeito antianginoso do alopurinol como terceiro medicamento para pacientes com doença arterial coronariana (DAC) estável. MÉTODOS: Trata-se de um ensaio clínico randomizado entre 2018 e 2020 incluindo pacientes com DAC que mantiveram angina apesar da otimização inicial com betabloqueadores e bloqueadores dos canais de cálcio. Os indivíduos foram randomizados 1:1 para 300 mg de alopurinol 2 vezes ao dia ou 35 mg de trimetazidina 2 vezes ao dia. O desfecho principal foi a diferença no domínio da frequência da angina do Questionário de Angina de Seattle (QAS-FA). Foram considerados estatisticamente significativos valores de probabilidade (p) < 0,05. RESULTADOS: Foram incluídos 108 pacientes na fase de randomização, com 54 (50%) no grupo alopurinol e 54 (50%) no grupo trimetazidina. Seis (5,6%) indivíduos, 3 de cada grupo, foram perdidos no seguimento para o desfecho primário. Nos grupos de alopurinol e trimetazidina, as pontuações medianas do QAS-FA foram 50 (30,0 a 70,0) e 50 (21,3 a 78,3), respectivamente. Em ambos os grupos, a pontuação do QAS-FA melhorou, mas a mediana da diferença em relação à linha de base foi menor no grupo alopurinol (10 [0 a 30] versus 20 [10 a 40]; p < 0,001), assim como a média da diferença na pontuação total do QAS (12,8 ± 17,8 versus 21,2 ± 15,9; p = 0,014). CONCLUSÃO: Tanto o alopurinol quanto a trimetazidina melhoraram o controle dos sintomas de angina; no entanto, a trimetazidina apresentou um ganho maior em relação à linha de base. Registro Brasileiro de Ensaios Clínicos ­ Número de Registro RBR-5kh98y.


Assuntos
Alopurinol , Trimetazidina , Vasodilatadores , Humanos , Alopurinol/uso terapêutico , Trimetazidina/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Vasodilatadores/uso terapêutico , Resultado do Tratamento , Idoso , Doença da Artéria Coronariana/tratamento farmacológico , Angina Pectoris/tratamento farmacológico
6.
BMC Nephrol ; 25(1): 266, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39164615

RESUMO

BACKGROUND: Uncontrolled gout can cause articular impairment but is also associated with a global and cardiovascular excess mortality, especially in dialysis population. Data documented within existing research is not conclusive regarding gout flares evolution during hemodialysis and their control by urate lowering therapy (ULT). Without clear guidelines concerning hemodialysis patients management with chronic gout, this study proposes to investigate whether gout flare incidence reduction could be observed on this population treated by urate lowering therapy versus patients without treatment. METHODS: We performed a retrospective cohort study in two hemodialysis centers in France. Were selected patients over 18 years old with a gout history who started hemodialysis between January 2005 and September 2015. Demographics and clinicals data were recorded at hemodialysis start and throughout 5 years of follow up. Gout flare was defined as presence of uric acid crystal in joint punction or clinically diagnosed as such with a colchicine prescription. All statistical analysis were performed in SAS® version 9.4 (SAS Institute Inc., Cary, NC). RESULTS: One hundred eighty-one patients have been included, mean age at dialysis initiation was 68.6 years (± 12.4) with 72% of men, 54% were treated by ULT: 89.7% by allopurinol and 9.3% by febuxostat. One patient received both treatments successively. After hemodialysis initiation, 35.36% patients had experienced at least one gout flare. The appearance of at least one gout flare concerned 50% of patients in no ULT group and 22.68% patients in ULT group (p = 0.0002). Dialysis efficiency was measured at regular interval during follow-up and was similar in both groups. To study the association strength between clinical factors and gout flares occurrences, a Cox model was performed; ULT is a protector factor of gout flare (HR:0,42, CI 95: 0,25-0,71). The proportion of serum urate values within the target (median 53% vs 29.3%, p < 0.0001) was significantly higher in ULT group versus no ULT group (median 53% vs 29.3%, p < 0.0001). CONCLUSION: Urate lowering therapy limit new gout flares occurrence in hemodialysis patients with gout historyCollaboration between rheumatologists and nephrologists may help to update guidelines for urate-lowering therapies in patients on dialysis.


Assuntos
Supressores da Gota , Gota , Diálise Renal , Exacerbação dos Sintomas , Ácido Úrico , Humanos , Masculino , Estudos Retrospectivos , Feminino , Gota/tratamento farmacológico , Gota/sangue , Idoso , Supressores da Gota/uso terapêutico , Pessoa de Meia-Idade , Ácido Úrico/sangue , Febuxostat/uso terapêutico , Alopurinol/uso terapêutico , Estudos de Coortes
8.
BMJ Open ; 14(8): e084665, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39097306

RESUMO

INTRODUCTION: Gout is one of the most common forms of arthritis worldwide. Gout is particularly prevalent in Aotearoa/New Zealand and is estimated to affect 13.1% of Maori men, 22.9% of Pacific men and 7.4% of New Zealand European men. Effective long-term treatment requires lowering serum urate to <0.36 mmol/L. Allopurinol is the most commonly used urate-lowering medication worldwide. Despite its efficacy and safety, the allopurinol dose escalation treat-to-target serum urate strategy is difficult to implement and there are important inequities in allopurinol prescribing in Aotearoa. The escalation strategy is labour intensive, time consuming and costly for people with gout and the healthcare system. An easy and effective way to dose-escalate allopurinol is required, especially as gout disproportionately affects working-age Maori men and Pacific men, who frequently do not receive optimal care. METHODS AND ANALYSIS: A 12-month non-inferiority randomised controlled trial in people with gout who have a serum urate ≥ 0.36 mmol/l will be undertaken. 380 participants recruited from primary and secondary care will be randomised to one of the two allopurinol dosing strategies: intensive nurse-led treat-to-target serum urate dosing (intensive treat-to-target) or protocol-driven dose escalation based on dose predicted by an allopurinol dosing model (Easy-Allo). The primary endpoint will be the proportion of participants who achieve target serum urate (<0.36 mmol/L) at 12 months. ETHICS AND DISSEMINATION: The New Zealand Northern B Health and Disability Ethics Committee approved the study (2022 FULL 13478). Results will be disseminated in peer-reviewed journals and to participants. TRIAL REGISTRATION NUMBER: ACTRN12622001279718p.


Assuntos
Alopurinol , Supressores da Gota , Gota , Ácido Úrico , Humanos , Alopurinol/administração & dosagem , Alopurinol/uso terapêutico , Gota/tratamento farmacológico , Gota/sangue , Nova Zelândia , Supressores da Gota/administração & dosagem , Supressores da Gota/uso terapêutico , Ácido Úrico/sangue , Masculino , Relação Dose-Resposta a Droga , Adulto , Estudos de Equivalência como Asunto , Feminino
9.
Georgian Med News ; (349): 68-71, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38963204

RESUMO

Hyperuricemia is an objective risk factor of derangement of fasting serum glucose and type 2 diabetes (T2D), yet whether hyperuricemia has a causative influence on insulin resistance is still debatable. In this study, we tested the hypothesis that lowering uric acid in hyperuricemic nondiabetic subjects might improve insulin resistance. Patients with renal stone and hyperuricemia (n=15) were recruited from the private clinic of Ib-Sina Local Teaching Hospital in Mosul city and prospectively placed on allopurinol (300mg/day) for 6 months. Serum uric acid (SUA), fasting serum glucose (FSG), fasting insulin, and C-peptide were measured using commercial kits. Results confirmed that allopurinol has significantly (P<0.05) reduced c-peptide and insulin together with a non-significant (p>0.05) reduction of serum glucose levels. In conclusion, allopurinol has improved insulin level and glycemic control in a healthy individual, these findings could be used as a template for using allopurinol in diabetic patients to improve glycemic control or future studies could be directed toward structural modification of allopurinol which hopefully might lead to innovation of new antidiabetic drugs.


Assuntos
Alopurinol , Glicemia , Hiperuricemia , Resistência à Insulina , Insulina , Cálculos Renais , Ácido Úrico , Humanos , Alopurinol/uso terapêutico , Cálculos Renais/tratamento farmacológico , Ácido Úrico/sangue , Insulina/sangue , Masculino , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Pessoa de Meia-Idade , Hiperuricemia/tratamento farmacológico , Hiperuricemia/sangue , Hiperuricemia/complicações , Feminino , Adulto , Peptídeo C/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue
10.
BMJ Open ; 14(7): e075741, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39053954

RESUMO

INTRODUCTION: Numerous studies, but not all, have suggested a positive effect of allopurinol on the cardiovascular system. The randomised, double-blind, placebo-controlled study evaluating the effect of allopurinol on the risk of cardiovascular events in patients with high and very high cardiovascular risk, including the presence of long-COVID-19 syndrome (ALL-VASCOR) study aims to evaluate the efficacy of allopurinol therapy for improving cardiovascular outcomes in patients at high and very high cardiovascular risk excluding ischaemic heart disease. This is particularly important due to the high cost of cardiovascular disease treatment and its status as one of the leading causes of mortality. METHODS AND ANALYSIS: The ALL-VASCOR study is a randomised, double-blind, placebo-controlled, multicentre trial that examines the effect of allopurinol therapy (200-500 mg of allopurinol daily) versus an equivalent dose of placebo on the risk of cardiovascular events in 1116 patients aged 40-70 with serum uric acid levels above 5 mg/dL at high and very high risk of cardiovascular disease. The ALL-VASCOR study will also assess the occurrence of long-COVID-19 syndrome. The study will measure primary and secondary as well as additional endpoints and the planned intervention will end on 31 July 2028 unless advised otherwise by the Safe Monitoring Board or other applicable authorities. Participant recruitment is planned to begin in March 2024 in Poland. ETHICS AND DISSEMINATION: The study was ethically approved by the Bioethics Committee of Poznan University of Medical Sciences (No 03/23, 12 January 2023). The results are expected after 2028 and will be disseminated in peer-reviewed journals and at international conferences. PROTOCOL VERSION NUMBER: 01-15 November 2022. TRIAL REGISTRATION NUMBER: EudraCT: 2022-003573-32, 27 October 2022, ClinicalTrials: NCT05943821, 13 July 2023.


Assuntos
Alopurinol , COVID-19 , Doenças Cardiovasculares , Humanos , Alopurinol/uso terapêutico , Método Duplo-Cego , Doenças Cardiovasculares/prevenção & controle , COVID-19/complicações , Idoso , Pessoa de Meia-Idade , Masculino , SARS-CoV-2 , Feminino , Adulto , Síndrome de COVID-19 Pós-Aguda , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco de Doenças Cardíacas
11.
Med Sci Monit ; 30: e944314, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38865287

RESUMO

BACKGROUND Hyperuricemia, which is common in chronic kidney disease and diabetes mellitus patients, raises health concerns. Febuxostat, a first-line urate-lowering agent, prompts cardiovascular risk questions, especially in high-risk patients. This study compared the effects of febuxostat and allopurinol on cardiovascular risk in diabetes mellitus and chronic kidney disease patients. MATERIAL AND METHODS This retrospective observational cohort study, conducted using Taiwan's National Health Insurance Research Database, focused on patients diagnosed with chronic kidney disease and diabetes between January 2012 and December 2017. The study population was divided into 2 groups: allopurinol users (n=12 901) and febuxostat users (n=2997). We performed 1: 1 propensity score matching, resulting in subgroups of 2997 patients each. The primary outcomes were assessed using a competing risk model, estimating hazard ratios (HR) for long-term outcomes, including the risks of all-cause hospitalization, hospitalization for heart failure, and hospitalization for cardiovascular interventions. RESULTS Febuxostat users, compared to allopurinol users, had higher all-cause hospitalization (HR: 1.33; 95% confidence interval [CI]: 1.25 to 1.42; P<.001), hospitalization for heart failure (HR: 1.62; 95% CI: 1.43 to 1.83; P<.001), and hospitalization for cardiovascular interventions (HR: 1.51; 95% CI: 1.32 to 1.74; P<.001). Moreover, the adverse effects of febuxostat on cardiac health were consistent across most subgroups. CONCLUSIONS Use of febuxostat in patients with diabetes mellitus and chronic kidney disease is associated with higher cardiovascular risks compared to allopurinol. Prudent evaluation is essential when recommending febuxostat for this at-risk group.


Assuntos
Alopurinol , Doenças Cardiovasculares , Febuxostat , Supressores da Gota , Hiperuricemia , Insuficiência Renal Crônica , Humanos , Febuxostat/uso terapêutico , Febuxostat/efeitos adversos , Alopurinol/uso terapêutico , Alopurinol/efeitos adversos , Masculino , Feminino , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Taiwan/epidemiologia , Hiperuricemia/tratamento farmacológico , Hiperuricemia/complicações , Supressores da Gota/uso terapêutico , Supressores da Gota/efeitos adversos , Diabetes Mellitus/tratamento farmacológico , Fatores de Risco , Adulto , Hospitalização
12.
Diabetes Metab Syndr ; 18(6): 103043, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38908114

RESUMO

AIMS: To assess the relationships between urate-lowering therapy (ULT) initiation with all-cause mortality in patients with asymptomatic hyperuricemia and Type 2 Diabetes (T2D). METHODS: This nationwide retrospective cohort study involved patients with T2D and asymptomatic hyperuricemia from 19 academic hospitals across China between 2000 and 2021. The primary exposure was ULT initiation, including allopurinol, febuxostat, or benzbromarone. The primary outcome was all-cause mortality. The secondary outcomes were cardiovascular (CV) and non-CV mortality. Propensity score matching was employed to create a 1:2 matched cohort with balanced likelihood of ULT initiation. Associations between ULT initiation with all-cause and CV mortality were assessed in the matched cohort. RESULTS: Among 42 507 patients, 5028 initiated ULT and 37 479 did not. In the matched cohort, comprising 4871 ULT initiators and 9047 noninitiators, ULT initiation was significantly associated with reduced risk of all-cause mortality (hazard ratio [HR] 0.77; 95% confidence interval [CI], 0.71-0.84), CV mortality (HR 0.86; 95% CI, 0.76-0.97), and non-CV mortality (HR 0.72; 95% CI, 0.64-0.80) over an average 3.0 years of follow-up. Among the ULT initiators, post-treatment SUA levels of 360-420 µmol/L was related to a significantly lower risk for all-cause mortality compared to levels >420 µmol/L (HR 0.74; 95% CI, 0.59-0.94) while levels ≤360 µmol/L did not (HR, 0.96; 95% CI, 0.81-1.14), suggesting a U-shaped relationship. CONCLUSIONS: Initiating ULT was associated with a significant reduction in all-cause mortality in patients with T2D and asymptomatic hyperuricemia. Notably, maintaining post-treatment SUA concentrations within 360-420 µmol/L could potentially enhance this reduced mortality.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperuricemia , Ácido Úrico , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/complicações , Hiperuricemia/mortalidade , Hiperuricemia/tratamento farmacológico , Hiperuricemia/sangue , Hiperuricemia/complicações , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Seguimentos , Ácido Úrico/sangue , Supressores da Gota/uso terapêutico , Idoso , Prognóstico , Taxa de Sobrevida , China/epidemiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Biomarcadores/sangue , Biomarcadores/análise , Alopurinol/uso terapêutico , Febuxostat/uso terapêutico , Benzobromarona/uso terapêutico
14.
Cardiol J ; 31(3): 479-487, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38771265

RESUMO

Xanthine oxidase inhibitors, including allopurinol and febuxostat, are the first-line treatment of hyperuricemia. This meta-analysis investigated the association between urate-lowering therapy and all-cause mortality in different chronic diseases to match its users and non-users in a real-world setting. Overall, 11 studies were included, which reported adjusted hazard ratios for all-cause mortality over at least 12 months. Meta-analysis of all included studies showed no effect of the therapy on all-cause mortality. However, subgroup analyses showed its beneficial effect in patients with chronic kidney disease (14% risk reduction) and hyperuricemia (14% risk reduction), but not in patients with heart failure (28% risk increase). Urate-lowering therapy reduces all-cause mortality among patients with hyperuricemia and chronic kidney disease, but it seems to increase mortality in patients with heart failure and should be avoided in this subgroup.


Assuntos
Causas de Morte , Hiperuricemia , Xantina Oxidase , Humanos , Xantina Oxidase/antagonistas & inibidores , Hiperuricemia/tratamento farmacológico , Hiperuricemia/mortalidade , Hiperuricemia/sangue , Causas de Morte/tendências , Inibidores Enzimáticos/uso terapêutico , Fatores de Risco , Alopurinol/uso terapêutico , Supressores da Gota/uso terapêutico , Febuxostat/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Ácido Úrico/sangue , Insuficiência Renal Crônica/mortalidade , Adulto
16.
Int J Rheum Dis ; 27(5): e15165, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38769820

RESUMO

OBJECTIVE: To compare the clinical efficacy of febuxostat combined with a low-purine diet versus allopurinol combined with a low-purine diet in the treatment of gout. METHODS: In this prospective controlled trial, 98 gout patients admitted to our hospital from February 2021 to December 2022 were enrolled as study subjects. Patients were randomly assigned to the study group (febuxostat combined with a low-purine diet) and the control group (allopurinol combined with a low-purine diet), with 49 patients in each group. The therapeutic effect was evaluated based on joint function and serum uric acid levels after treatment, and classified into three levels: markedly effective, effective, and ineffective. The levels of inflammatory factors, including tumor necrosis factor-a (TNF-a), cytokine interleukin-1beta (IL-1ß), and interleukin (IL)-18 (IL-18), were collected. The Numeric Rating Scale (NRS) was used to assess the degree of pain in patients. Clinical indicators before and 6 months after treatment were compared between the two groups. RESULTS: There was no statistically significant difference in age and gender between the two groups. After 6 months of treatment, the effective rate in the study group (48 cases, 97.96%) was higher than that in the control group (42 cases, 85.71%), with a statistically significant difference (p = .027). At the same time, the study group had significantly lower levels of serum uric acid (162.39 µmol/L ± 17.23 µmol/L vs. S198.32 µmol/L ± 18.34 µmol/L, p < .001), creatinine (87.39 mmol/L ± 9.76 mmol/L vs. 92.18 mmol/L ± 9.27 mmol/L, p = .014), total cholesterol (3.65 mmol/L ± 0.65 mmol/L vs. 4.76 mmol/L ± 0.73 mmol/L, p < .001), and triglycerides (1.76 mmol/L ± 0.32 mmol/L vs. 2.28 mmol/L ± 0.41 mmol/L, p < .001) compared to the control group, with statistically significant differences (p < .05). After treatment, the levels of inflammatory factors and degree of pain in the study group were significantly lower than those in the control group (all p < .05). During the treatment process, the incidence of adverse reactions in the study group (2 cases, 4.08%) was lower than that in the control group (9 cases, 18.37%), with a statistically significant difference (p = .025). CONCLUSION: Febuxostat combined with a low-purine diet can reduce inflammatory factors and alleviate the degree of pain in gout patients, significantly improving their clinical symptoms.


Assuntos
Alopurinol , Febuxostat , Supressores da Gota , Gota , Ácido Úrico , Humanos , Febuxostat/uso terapêutico , Febuxostat/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Alopurinol/uso terapêutico , Gota/tratamento farmacológico , Gota/sangue , Gota/diagnóstico , Supressores da Gota/uso terapêutico , Supressores da Gota/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento , Ácido Úrico/sangue , Idoso , Purinas/uso terapêutico , Biomarcadores/sangue , Terapia Combinada , Fatores de Tempo , Adulto , Mediadores da Inflamação/sangue
17.
Brain Res Bull ; 213: 110973, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38723694

RESUMO

Epilepsy is a common neurological disease characterized by the recurrent, paroxysmal, and unprovoked seizures. It has been shown that hyperuricemia enhances and associated with the development and progression of epilepsy through induction of inflammation and oxidative stress. In addition, uric acid is released within the brain and contributes in the development of neuronal hyperexcitability and epileptic seizure. Brain uric acid acts as damage associated molecular pattern (DAMP) activates the immune response and induce the development of neuroinflammation. Therefore, inhibition of xanthine oxidase by allopurinol may reduce hyperuricemia-induced epileptic seizure and associated oxidative stress and inflammation. However, the underlying mechanism of allopurinol in the epilepsy was not fully elucidated. Therefore, this review aims to revise from published articles the link between hyperuricemia and epilepsy, and how allopurinol inhibits the development of epileptic seizure.


Assuntos
Alopurinol , Epilepsia , Hiperuricemia , Hiperuricemia/tratamento farmacológico , Alopurinol/farmacologia , Alopurinol/uso terapêutico , Humanos , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Animais , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ácido Úrico/metabolismo , Xantina Oxidase/metabolismo , Xantina Oxidase/antagonistas & inibidores , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos
19.
Rheumatology (Oxford) ; 63(9): 2433-2441, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38733596

RESUMO

OBJECTIVES: To compare the risk of urolithiasis in gout patients initiating allopurinol, a xanthine oxidase inhibitor, vs benzbromarone, a uricosuric. METHODS: Using the 2011-20 Korea National Health Insurance Service database, we conducted a cohort study on gout patients initiating allopurinol vs benzbromarone as the first-line urate-lowering treatment. The primary outcome was a new onset urinary stone. The secondary outcome was a stone requiring intervention. We estimated hazard ratios (HRs) and 95% CIs using Cox proportional hazard models with a 5:1 ratio propensity-score matching on >80 variables. Subgroup analyses were done by age, sex, thiazide use and cardiovascular risk. RESULTS: 61 300 allopurinol initiators PS-matched on 12 260 benzbromarone initiators were included (mean age 59 years, 79% male). During a mean follow-up of 322 days, 619 urolithiasis cases occurred with an incidence rate of 0.87 per 100 person-years in allopurinol and 1.39 in benzbromarone initiators, showing a HR of 0.64 (95% CI, 0.51-0.80). Approximately 44% of urinary stones required intervention with a HR of 0.61 (95% CI, 0.43-0.88). The lower risk associated with allopurinol compared with benzbromarone persisted across subgroups but was greater in the high than non-high cardiovascular risk subgroup (P for interaction = 0.02). CONCLUSION: This population-based cohort study found that allopurinol compared with benzbromarone was associated with a substantially lower risk of urolithiasis particularly in the presence of the high cardiovascular risk. This finding provides important safety information for clinicians' decision-making on urate-lowering treatments of different mechanisms of action.


Assuntos
Alopurinol , Benzobromarona , Supressores da Gota , Gota , Urolitíase , Humanos , Benzobromarona/uso terapêutico , Benzobromarona/efeitos adversos , Alopurinol/uso terapêutico , Alopurinol/efeitos adversos , Gota/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Urolitíase/induzido quimicamente , Urolitíase/epidemiologia , Supressores da Gota/uso terapêutico , Supressores da Gota/efeitos adversos , Idoso , República da Coreia/epidemiologia , Uricosúricos/uso terapêutico , Estudos de Coortes , Incidência , Modelos de Riscos Proporcionais , Fatores de Risco , Adulto
20.
Schweiz Arch Tierheilkd ; 166(4): 207-215, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572822

RESUMO

INTRODUCTION: This case report describes the long-term success of a subcutaneous ureteral bypass device in a dog for treatment of a ureteral obstruction. The suspected xanthine urolithiasis was secondary to treatment with allopurinol for leishmaniasis. The dog presented initially with lethargy, anuria and abdominal pain. Mild azotemia was found on biochemical analysis and abdominal ultrasound revealed bilateral ureteral obstruction. A subcutaneous ureteral bypass was subsequently placed using a standard surgical technique. The dog recovered uneventfully and the azotemia resolved within days. Follow-up examinations were performed every trimester for over three years and no complications like obstruction of the bypass tubes, urinary tract infection or azotemia were recognized during this follow-up period. Allopurinol was replaced with domperidone as long-term treatment against Leishmaniasis which resulted in a mild increase of the leishmania serum antibody titer. The subcutaneous ureteral bypass placement was successful and safe in this dog and is a valuable alternative in cases of ureteral obstruction also in dogs.


INTRODUCTION: Ce rapport de cas décrit le succès à long terme d'une dérivation urétérale sous-cutanée chez un chien pour le traitement d'une obstruction urétérale. L'urolithiase xanthique suspectée était secondaire à un traitement à l'allopurinol contre la leishmaniose. Le chien a d'abord présenté une léthargie, une anurie et des douleurs abdominales. L'analyse biochimique a révélé une légère azotémie et l'échographie abdominale a révélé une obstruction urétérale bilatérale. Une dérivation urétérale sous-cutanée a été mise en place selon une technique chirurgicale standard. Le chien s'est rétabli sans incident et l'azotémie a disparu en quelques jours. Des examens de suivi ont été effectués tous les trimestres pendant plus de trois ans et aucune complication telle qu'une obstruction du tube de dérivation, une infection urinaire ou une azotémie n'a été constatée au cours de cette période de suivi. L'allopurinol a été remplacé par de la dompéridone dans le cadre d'un traitement à long terme contre la leishmaniose, ce qui a entraîné une légère augmentation du titre des anticorps sériques contre la leishmaniose. La mise en place d'une dérivation urétérale sous-cutanée s'est avérée efficace et sûre chez ce chien et constitue une alternative intéressante en cas d'obstruction urétérale, y compris chez les chiens.


Assuntos
Azotemia , Doenças do Gato , Doenças do Cão , Leishmaniose , Obstrução Ureteral , Urolitíase , Animais , Cães , Gatos , Obstrução Ureteral/etiologia , Obstrução Ureteral/cirurgia , Obstrução Ureteral/veterinária , Alopurinol/uso terapêutico , Azotemia/veterinária , Urolitíase/cirurgia , Urolitíase/veterinária , Leishmaniose/veterinária , Xantinas , Stents/veterinária , Doenças do Cão/tratamento farmacológico , Doenças do Cão/cirurgia
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