A review of uric acid, crystal deposition disease, and gout.
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ABSTRACT:
SUBMITTER: Perez-Ruiz F
PROVIDER: S-EPMC4311063 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundUric acid (UA) is an endogenous antioxidant which is known to reduce oxidative stress and also chelate iron ion. Recent studies have provided evidence that UA may play a neuroprotective role in Parkinson's disease (PD). However, it is unknown whether UA relates to nigral iron deposition, which is a characteristic pathophysiological alteration in PD. The aim of this study was to determine the potential relationship of these two markers in patients with PD.MethodsA total of 30 patients of PD and 25 age- and gender- matched healthy controls underwent 3-Tesla MRI and laboratory tests including serum UA levels. We assessed iron levels by measuring phase shift values using susceptibility-weighted image. Mean phase shift values of the substantia nigra (SN), red nucleus, head of the caudate nucleus, globus pallidus, putamen, thalamus, and frontal white matter were calculated and correlated with serum UA levels.ResultsSerum UA levels were significantly decreased in the PD patients than in the controls. Phase shift values in bilateral SN were significantly increased in the PD patients than in the controls. There was no significant correlation between serum UA levels and nigral phase shift values.ConclusionsAs previous studies, low serum UA level and increased nigral iron content in the PD was reconfirmed in this study. However, we failed to find the relationship between these two markers. Our data suggest that serum UA may not be important determinant of nigral iron deposition in PD.
| S-EPMC4227693 | biostudies-literature
Project description:Hyperuricemia often accompanies hypertension, diabetes, dyslipidemia, metabolic syndrome, and chronic renal disease; it is also closely related to cardiovascular disease. Moreover, several epidemiological studies have linked hyperuricemia and ischemic stroke. However, uric acid may also have neuroprotective effects because of its antioxidant properties. An association between low uric acid levels and neurodegenerative diseases has been suggested, which may be attributed to diminished neuroprotective effects as a result of reduced uric acid. This review will focus on the relationship between uric acid and various neurological diseases including stroke, neuroimmune diseases, and neurodegenerative diseases. When considering both the risk and pathogenesis of neurological diseases, it is important to consider the conflicting dual nature of uric acid as both a vascular risk factor and a neuroprotective factor. This dual nature of uric acid is important because it may help to elucidate the biological role of uric acid in various neurological diseases and provide new insights into the etiology and treatment of these diseases.
| S-EPMC10268604 | biostudies-literature
Project description:As a prominent feature of gout, monosodium urate (MSU) crystal deposition can induce gout flare, yet its impact on blood immune in gout remission patients still remains unclear. In this study, single-cell RNA sequencing (scRNA-seq) is used to compare the gene expression profiling of peripheral blood mononuclear cells (PBMCs) among intercritical gout remission patients, advanced gout remission patients and healthy volunteers. The increase of HLA-DQA1high classical monocytes, and their important role in immune inflammatory responses and osteoclast differentiation are discovered in advanced gout remission patients. Moreover, the differentiation level of CD8+T cells are found to elevate in advanced gout remission patients, which is further validated via flow cytometry. It is also observed that pathways related to bone metabolism and inflammatory responses are overactive in advanced gout remission patients. By analysis on intercellular communication network, immune-related cell-cell interactions among PBMCs are shown to enhance in both intercritical and advanced gout remission patients. The analyses on gene expression and LC-MS/MS together indicate the increased metabolic level of arachidonic acid in gout remission patients with MSU deposition at the intercritical and advanced stage. The study reveals distinctive blood immune characteristics in gout remission with MSU deposition, which provides more sights into its pathogenesis.
2023-06-01 | GSE217561 | GEO
Project description:Gout is a chronic disease associated with deposition of monosodium urate crystals and accompanied by diabetes, hypertension, and dyslipidemia. Hypertriglyceridemia is common among patients with gout, and fenofibrate is usually used to reduce triglyceride levels. The aim of this study is to determine the effect of uric acid reduction by fenofibrate in patients with gout administered uric acid lowering agents (viz., the xanthine oxidase inhibitors allopurinol and febuxostat). Data from 863 patients with gout were collected from electronic medical records comprising information on underlying diseases, laboratory findings, and drug histories. Among all the patients, 70 (8.11%) took fenofibrate with allopurinol or febuxostat. Male and young patients took fenofibrate more frequently, and hypertension was less frequent in patients administered xanthine oxidase inhibitors and fenofibrate than in those administered only xanthine oxidase inhibitors. After the treatment, serum uric acid levels more significantly decreased (-1.81?±?2.41 vs. -2.40?±?2.28?mg/dL, p?=?0.043) in patients with fenofibrate cotreatment, than in those administered allopurinol or febuxostat alone. The effect of uric acid reduction was larger (b?=?-1.098, p?<?0.001) in patients taking glucocorticoids than in those administered other treatments. There was no difference in the levels of creatinine, blood urea nitrogen, and aminotransferases between patients treated with and without fenofibrate. Fenofibrate additionally reduced uric acid levels without showing any change in the results of renal or liver function tests, suggesting that the addition of fenofibrate is a reasonable option for treating gout in patients having high triglyceride levels.
| S-EPMC6233215 | biostudies-literature
Project description:Uric acid urolithiasis constitutes approximately 7-10% of all urinary stones. Previous studies have revealed that patients with gout do not equally have uric acid stones. Instead, the risk of gout in patients with uric acid stones remains controversial. This study aimed to investigate whether there is different associated risk of gout for diabetes mellitus (DM) and non-diabetes patients with uric acid urolithiasis. Therefore, we examined all baseline chemistries to determine any risk factors or protective factors related to developing gout in patients with uric acid stones. Ninety-nine patients from a single medical center, who had a uric acid component in their stone specimen were enrolled and their medical records were reviewed retrospectively between January 2010 and December 2016. All patients were divided into gout and non-gout groups. Gout was confirmed in 24 patients in this study (24.2%). The proportion of DM was significantly higher in the non-gout group (34.7%) than in the gout group (4.3%, p < 0.05). Renal function was decreased and serum triglyceride was higher in patients with gout. Uric acid urolithiasis patients with DM had a lower risk for gout (adjusted odds ratio: 0.08; 95% confidence interval (CI) = 0.01-0.61, p = 0.015). In 89 patients with predominant uric acid stones (>50% uric acid composition), the risk for gout was still lower in patients with diabetes than non-diabetes (adjusted odds ratio: 0.08; 95% confidence interval (CI) = 0.01-0.61, p = 0.015). These findings suggest that decreased risk of gout is found in uric acid urolithiasis patients with diabetes. Our results imply that patients with uric acid stones should have complete diabetes evaluation before the administration of uric acid controlling medication.
| S-EPMC6832126 | biostudies-literature
Project description:BackgroundThere is little evidence guiding selection of nondiuretic, antihypertensive agents with a goal of lowering uric acid (SUA) and minimizing gout risk.MethodsIn the African American Study of Kidney Disease and Hypertension (AASK) trial, African Americans with chronic kidney disease were randomly assigned to metoprolol (a beta-blocker), ramipril (an angiotensin-converting enzyme inhibitors [ACEi]), or amlodipine (a dihydropyridine calcium-channel blocker). SUA was measured at baseline and 12 months. Gout-related hospitalizations were based on ICD9 codes. Gout-related medication use (GRMs) was based on active prescriptions of allopurinol, colchicine, or probenecid during the baseline visit of the AASK cohort phase. We examined the effect of drug assignment on 12-month SUA (linear regression), gout-related hospitalization (Cox regression), and GRM (logistic regression).ResultsOf the 630 participants, 40% were female with a mean age of 55 years (SD, 10), mean SUA of 8.2 mg/dl (2.0), and mean serum creatinine of 1.8 mg/dl (0.6). After 12 months, metoprolol increased SUA by 0.3 mg/dl, while ramipril or amlodipine had no effect on SUA. Compared to ramipril, metoprolol significantly increased 12-month SUA (0.40; 0.10, 0.70 mg/dl; P = 0.009), nonsignificantly increased risk of gout-related hospitalization (hazard ratio: 3.87; 0.82, 18.26; P = 0.09), and significantly increased the odds of GRM (odds ratio: 1.62; 1.03, 2.54; P = 0.04). While metoprolol was associated with a higher 12-month SUA compared with amlodipine (0.57; 0.18, 0.95; P = 0.004), there was no difference in gout-related hospitalizations or GRM.ConclusionsMetoprolol increased SUA and GRM in African American adults. Health professionals treating patients with kidney disease at risk for gout should avoid metoprolol and possibly consider an ACEi.Clinical trials registrationTrial Number NCT00582777.
| S-EPMC5861578 | biostudies-literature
Project description:BackgroundRecently, a large meta-analysis including over 28,000 participants identified nine different loci with association to serum uric acid (UA) levels. Since elevated serum UA levels potentially cause gout and are a possible risk factor for coronary artery disease (CAD) and myocardial infarction (MI), we performed two large case-control association analyses with participants from the German MI Family Study. In the first study, we assessed the association of the qualitative trait gout and ten single nucleotide polymorphisms (SNP) markers that showed association to UA serum levels. In the second study, the same genetic polymorphisms were analyzed for association with CAD.Methods and findingsA total of 683 patients suffering from gout and 1,563 healthy controls from the German MI Family Study were genotyped. Nine SNPs were identified from a recently performed genome-wide meta-analysis on serum UA levels (rs12129861, rs780094, rs734553, rs2231142, rs742132, rs1183201, rs12356193, rs17300741 and rs505802). Additionally, the marker rs6855911 was included which has been associated with gout in our cohort in a previous study. SNPs rs734553 and rs6855911, located in SLC2A9, and SNP rs2231142, known to be a missense polymorphism in ABCG2, were associated with gout (p=5.6*10(-7), p=1.1*10(-7), and p=1.3*10(-3), respectively). Other SNPs in the genes PDZK1, GCKR, LRRC16A, SLC17A1-SLC17A3, SLC16A9, SLC22A11 and SLC22A12 failed the significance level. None of the ten markers were associated with risk to CAD in our study sample of 1,473 CAD cases and 1,241 CAD-free controls.ConclusionSNP markers in SLC2A9 and ABCG2 genes were found to be strongly associated with the phenotype gout. However, not all SNP markers influencing serum UA levels were also directly associated with the clinical manifestation of gout in our study sample. In addition, none of these SNPs showed association with the risk to CAD in the German MI Family Study.
| S-EPMC2766838 | biostudies-literature
Project description:Evidence strongly suggests that delivery of gout care is suboptimal. The 2012 American College of Rheumatology (ACR) guidelines emphasize a serum uric acid (SUA) target of <6 mg/dl when utilizing urate-lowering therapy (ULT). However, the proportion and characteristics of Americans with gout receiving ULT, or with a ULT indication, who are achieving this target is unknown.We identified US adults with gout receiving ULT, and those with an indication for ULT, using the National Health and Nutrition Examination Surveys from 2007-2010. Using the ACR guidelines, a ULT indication comprised chronic kidney disease (CKD) stage 2-5, a history of nephrolithiasis, or current ULT use. Demographic and clinical factors associated with an SUA ?6 mg/dl were determined using Poisson regression.In 2007-2010, an estimated 4.5 million US adults with gout had an indication for ULT; two-thirds had an SUA ?6 mg/dl. In adjusted analyses among those with gout and CKD or nephrolithiasis, those age ?70 years were less likely (prevalence ratio [PR] 0.77, 95% confidence interval [95% CI] 0.61-0.97) to have an SUA ?6 mg/dl. Regarding those taking ULT, hypertension was related to a reduced prevalence (PR 0.51, 95% CI 0.30-0.87), whereas diabetes mellitus (PR 1.42, 95% CI 1.06-1.90) and obesity (PR 1.74, 95% CI 1.19-2.56) were each associated with a higher prevalence of an SUA value ?6 mg/dl.Half of all Americans with gout receiving ULT, and two-thirds with an indication for ULT, have an SUA above target. This study furnishes a meaningful baseline for assessing the effectiveness of the ACR guidelines in future years.
| S-EPMC4362996 | biostudies-literature
Project description:BackgroundSi-Miao-San (SMS) is a well-known traditional Chinese medicine. This study aims to evaluate the anti-inflammatory effects of SMS on gouty arthritis and its potential mechanism of action.MethodsThe effects and mechanism of SMS were evaluated in monosodium urate (MSU)-treated mice or macrophages. The expression of cytokines and PI3K/Akt was analyzed using real-time PCR and Western blotting analyses. Macrophage polarization was assessed with immunofluorescence assays, real-time PCR, and Western blotting. Mass spectrometry was used to screen the active ingredients of SMS.ResultsPretreatment with SMS ameliorated MSU-induced acute gouty arthritis in mice with increased PI3K/Akt activation and M2 macrophage polarization in the joint tissues. In vitro, SMS treatment significantly inhibited MSU-triggered inflammatory response, increased p-Akt and Arg-1 expression in macrophages, and promoted M2 macrophage polarization. These effects of SMS were inhibited when PI3K/Akt activation was blocked by LY294002 in the macrophages. Moreover, SMS significantly reduced serum uric acid levels in the hyperuricemia mice. Using mass spectrometry, the plant hormones ecdysone and estrone were detected as the potentially effective ingredients of SMS.ConclusionSMS ameliorated MSU-induced gouty arthritis and inhibited hyperuricemia. The anti-inflammatory mechanism of SMS may exert anti-inflammatory effects by promoting M2 polarization via PI3K/Akt signaling. Ecdysone and estrone might be the potentially effective ingredients of SMS. This research may provide evidence for the application of SMS in the treatment of gout.
| S-EPMC8769502 | biostudies-literature
Project description:Andrographis paniculata (Burm.f.) Nees has been found to have anti-inflammatory and immunostimulatory effects. This study was to investigate antihyperuricemic and anti-inflammatory effects of A. paniculata leaf extracts. Andrographolide, 14-deoxy-11,12-didehydroandrographolide, and neoandrographolide were quantified in 80% ethanol (EtOH80) and water extracts using High Performance Liquid Chromatography (HPLC) analysis. Antihyperuricemic activity was evaluated using a spectrophotometric in vitro inhibitory xanthine oxidase (XO) assay. The most active extract and andrographolide were further investigated in a hyperuricemic rat model induced by potassium oxonate to determine serum uric acid levels, liver XO activity, followed by Western blot analysis for renal urate transporter URAT1, GLUT9, and OAT1 to investigate the excretion of uric acid via kidney. Anti-inflammatory activity was assessed by in vitro interleukin assay for interleukin (IL-1α, IL-1β, IL-6, IL-8), and tumor necrosis factor (TNF-α) in monosodium urate (MSU) crystal-induced human fibroblast-like synoviocyte (HFLS) cells using ELISA-kits, followed by Western blot analysis for the expression of MyD88, NLRP3, NF-κB p65, and caspase-1 proteins to investigate the inflammation pathway. In vivo assay of the most active extract and andrographolide were performed based on the swelling rate and inhibition of pro-inflammatory mediator release from synovial fluid of a rat knee joint induced by MSU crystals. The results showed that the EtOH80 extract had a greater amount of andrographolide (11.34% w/w) than the water extract (1.38% w/w). In the XO inhibitory activity, none of the samples exhibited greater than 50% inhibition. However, in a rat model, EtOH80 extract (200 mg/kg/day) and andrographolide (30 mg/kg/day) decreased serum uric acid levels and reduced liver XO activity, reduced the protein expression levels of URAT1 and GLUT9, and restored the decrease in OAT1 levels. In the in vitro anti-inflammatory study, EtOH80 extract and andrographolide significantly decreased production of IL-1α, IL-1β, IL-6, and TNF-α, as well as inhibited the synthesis of MyD88, NLRP3, NF-κB p65, and caspase-1 in a concentration-dependent manner, almost comparable to dexamethasone. The EtOH80 extract (200 mg/kg/day) and andrographolide (30 mg/kg) significantly decreased swelling rate and IL-1α, IL-1β, IL-6, and TNF-α in the synovial fluid of rat models in a time-dependent manner, comparable to indomethacin (3 mg/kg/day). In conclusion, the findings show that EtOH80 extract has a substantial anti-gout effect by lowering uric acid levels and suppressing pro-inflammatory mediator production due to the andrographolide content, that might be beneficial in the treatment of gouty-inflammation.
| S-EPMC8793851 | biostudies-literature