Role Of Uric Acid Research Articles

Correlation of Serum Uric Acid with Cognition, Severity, and Stage of Disease in Patients with Idiopathic Parkinson’s Disease and Vascular Parkinsonism: A Cross-Sectional Study

Background: Uric acid (UA) being a potent antioxidant may reduce the oxidative stress and progression of Parkinson’s disease. However, the role of UA is not yet established in people with Idiopathic Parkinson’s disease (IPD) and Vascular Parkinsonism (VP). Objectives: We aimed i) to compare the serum UA levels in IPD, VP, and healthy adults and ii) to find a relation between UA levels with disease severity, disease stage, and cognitive function in people with IPD and VP. Methods: A cross-sectional study was conducted among people with IPD (n=70), VP (n=70), and healthy adults (n=70). Demographics details, body mass index, duration of illness, levodopa usage, comorbidities, MDS-UPDRS scores, modified H&Y scale, MMSE, and serum UA levels were collected from participants. Pearson’s correlation coefficient was used to find the correlation between UA levels, MDS-UPDRS, H & Y, and MMSE scores. Results: The age of the participants ranged from 59 to 80 years. Results showed that serum UA level in healthy control (5.41±0.99; p=0.001) and VP groups (5.27 ± 0.99; p=0.001) were significantly higher compared to IPD group (4.34 ±1.03). We found a significant negative correlation between UA and MDS-UPDRS (r=-0.68, p<0.01) and H & Y scores (r = -0.61, p<0.01) and a significant positive correlation of UA with MMSE (r=0.55, p<0.01) in the IPD group. UA levels in the VP group were not correlated with any of the outcome measures. Conclusion: In people with IPD, serum UA level was negatively correlated with severity and progression of the disease but positively correlated with cognitive ability.

The Role of Uric Acid as an Antioxidant in Selected Neurodegenerative Disease Pathogenesis

Uric acid, a potent antioxidant for humans, birds, reptiles, and some primate species, is the end-product of purine degradation that is formed in the xanthine/hypoxanthine reactions catalyzed by xanthine oxidase. Associated with the evolutionary loss of urate oxidase (the enzyme that oxidizes uric acid resulting in the formation of allantoin) and resulting increase in concentrations of uric acid is a prolonged life span. Uric acid is known to scavenge peroxynitrite and other free radicals that can cause an imbalance of oxidants leading to oxidative stress. Uric acid also has a role in protecting DNA from single-strand breaks caused by free radicals in the body leading to a protective effect in neurodegenerative diseases. The brain is particularly vulnerable to oxidative stress as it is considered an ‘expensive tissue’ with a particularly high metabolic rate and comparatively increased utilization of oxygen. Brain tissue is also high in unsaturated lipids, which makes it more susceptible to free radical damage. Oxidative stress is thus linked to the pathogenesis of neurodegenerative diseases and also ischemic brain injury. In this review, we summarize the function of uric acid in alleviating oxidative damage and providing protection to neural cells during injury and disease.

FC027: Uric Acid Stimulates Cytoskeleton Pathways in Vascular Smooth Muscle Cells Through F-ACTIN Polymerization and Atrogin, Αsma and SM22 up Regulation

Abstract BACKGROUND AND AIMS Hyperuricaemia (HU) has been identified as a risk factor for hypertension and renal disease. The most widely documented pathogenetic mechanisms for the uric acid (UA) mediated vascular and renal damage are vascular inflammation and remodeling. Vascular smooth muscle cells (VSMCs) possess a distinctive property of plasticity that allows the phenotypic transition and contributes to vascular remodeling. The aim of this study was to investigate UA effects on VSMC cell line, focusing on phenotypic transition and searching for possible signals involved in this process. METHOD MOVAS, a mouse VSMC cell line, was exposed for short (0–6 h) or long time (24–48 h) to 0 (No Treated cells: NT), 6, 9 and 12 mg/dL of UA, respectively. We evaluated cell viability by MTT test, migration property in a 48-well microchemotaxis chamber (using an 8 μm pore size, polycarbonate polyvinylpyrrolidone-free filters) and by phalloidin staining. Changes in cytoskeleton proteins [Smoothelin (SMT), alpha-Smooth Muscle Actin (αSMA), Smooth Muscle 22 Alpha (SM 22α)] were detected by real time polymerase chain reaction (rt-PCR) and Western blot. In addition, we evaluated angiotensin receptor 1 (AT1) and atrogin 1 expression by rt-PCR and Map kinase activation (Erk 1,2) by western blot. Lastly, we tested the UA effects on cellular changes through a prior treatment with angiotensin receptor blockers, Valsartan (V) and Losartan (L) 10 µmol. RESULTS A small increment in cell proliferation was observed at 24 h (+11%–15%; P < 0.05). UA promoted an increased migratory rate in UA treated VSMCs at 24 and 48 h respect to untreated cells (P < 0.001). These results were confirmed by F-actin intracellular distribution: the AlexaFluor 594-conjugate-phalloidin staining revealed a compact polymerization of F-actin in stress fibers along the major cell axis in untreated cells, while a re-arrangement in thinner and poorly oriented fibers localized at cortical level were found in UA treated cells (Fig. 1). When we evaluated cytoskeleton components, we found out that 24 h UA exposition rose up, SMT (2.5–3.4-fold; P < 0.05), αSMA (1.3–1.5-fold; P < 0.05) and SM 22α levels (1.3–2.5-fold P < 0.05). Conversely, we found a 48 h UA treatment caused them to drop (SMT = –20%–40%, P < 0.05; αSMA = –20%–40%, P < 0.05; SM 22α = –30%–43%, P < 0.05). Atrogin-1 was 2-fold up regulated at 48 h in UA treated VMSCs compared with NT (P = 0.04), suggesting a possible role for UA in cytoskeleton remodeling (Fig. 2). Furthermore, we observed a significant increase in VSMC area (+30%; P < 0.001) regardless of UA concentration and time exposition. Supposing a key role of Angiotensin involvement in UA induced VSMCs changes, AT1 expression was assessed. We found AT1 was up regulated in UA treated VSMCs compared with NT (P = 0.04). As expected, V and L had inhibitory effects on AT1 upregulation. Moreover, the two angiotensin receptors blockers inhibited all the phenotypic changes induced by UA. Lastly, UA induced a time dependent Erk 1, 2 phosphorylation (1.5–2.5-fold versus T0; P < 0.05–0.01), which was reversed by both L and V. CONCLUSION The results of this study show for the first time as UA-induced cytoskeletal changes involve polymerization of F-actin, Atrogin, αSMA and up-regulation of SM22.These results reveal the pathways by which UA induces an increase in VSMC area and in migratory rate, suggesting UA as a key player in vascular remodeling.

The Influence of Serum Uric Acid on the Brain and Cognitive Dysfunction.

Uric acid is commonly known for its bad reputation. However, it has been shown that uric acid may be actively involved in neurotoxicity and/or neuroprotection. These effects could be caused by oxidative stress or inflammatory processes localized in the central nervous system, but also by other somatic diseases or systemic conditions. Our interest was to summarize and link the current data on the possible role of uric acid in cognitive functioning. We also focused on the two putative molecular mechanisms related to the pathological effects of uric acid—oxidative stress and inflammatory processes. The hippocampus is a prominent anatomic localization included in expressing uric acid's potential impact on cognitive functioning. In neurodegenerative and mental disorders, uric acid could be involved in a variety of ways in etiopathogenesis and clinical presentation. Hyperuricemia is non-specifically observed more frequently in the general population and after various somatic illnesses. There is increasing evidence to support the hypothesis that hyperuricemia may be beneficial for cognitive functioning because of its antioxidant effects but may also be a potential risk factor for cognitive dysfunction, in part because of increased inflammatory activity. In this context, gender specificities must also be considered.

The Role Of Uric Acid And Hscrp In Predicting Metabolic Syndrome

Aim: Metabolic syndrome is a group of diseases characterized by the coexistence of cardiometabolic risk factors such as abdominal obesity, dyslipidemia, glucose intolerance, and high blood pressure. Metabolic syndrome is a common disease that can lead to high mortality with cardiovascular complications. Many studies are ongoing for laboratory parameters that can be used in the early diagnosis of this syndrome, but for daily clinical use and the diagnostic criteria, any parameter has not been revealed yet. We planned to carry out this study to predict the usability of uric acid and HSCRP in clinical practice, which have been reported to be associated with metabolic syndrome in the literature. Material and Methods: Patients with metabolic syndrome who applied to Ankara Training and Research Hospital’s Internal Medicine department outpatient clinic for any reason within nine months were included in the study group. In the same period, completely healthy cases who applied to the outpatient clinic for any reason were included in the control group. Demographic data, physical examination findings, anthropometric measurement results, biochemical parameters, and HSCRP levels of the cases were recorded. Metabolic syndrome and the control group were analyzed for uric acid and HSCRP values. SPSS 25.0 was used for statistical analysis. The data were evaluated within the 95% confidence interval, and p<0.05 was considered significant. Results: In the study conducted that with a total of 174 patients, including 95 patients with metabolic syndrome and 79 healthy patients, the mean uric acid level of the metabolic syndrome group (5.22±1.39mg/dl) was significantly higher than that of the control group (4.35±1.11mg/dl) (p<0.01). With the ROC curve, the uric acid cut-off value for detecting metabolic syndrome incidence was found to be 5.45mg/dl (specificity 89.9%; sensitivity 51.6%). Its positive predictive value was 86%, and its negative predictive value was 60.7%. The mean HSCRP levels of the metabolic syndrome group (4.72±3.54mg/L) were found to be significantly higher than the control group (3.30±3.21mg/L) (p<0.01). Conclusion: Serum uric acid and HSCRP levels in the study group with metabolic syndrome were significantly higher than in the control group. This syndrome, which is very common today, can lead to various outcomes in terms of mortality and morbidity; when the early diagnosis is delayed, it constitutes an important part of health expenditures. We believe that early diagnosis with laboratory parameters that can be very practical in daily practice will prevent metabolic syndrome complications. Keywords : Metabolic syndrome, obesity, systemic inflammation, uric acid, HSCRP

Uric acid and cardiovascular risk stratification in the acute coronary syndromes: a friend we should mind

Uric acid (UA) is the end product of purine metabolism. Whilst being primarily known as the leading risk factor for the onset of gout [ [1] Dalbeth N. Choi H.K. Joosten L.A.B. Khanna P.P. Matsuo H. Perez-Ruiz F. Stamp L.K. Gout. Nat Rev Dis Primers. 2019; 5 Crossref PubMed Scopus (114) Google Scholar ], UA has also been acknowledged as a significant CV risk factor [ [2] Virdis A. Masi S. Casiglia E. et al. Identification of the uric acid thresholds predicting an increased total and cardiovascular mortality over 20 years. Hypertension. 2020; 75: 302-308 Crossref PubMed Scopus (62) Google Scholar ]. However, international guidelines report as pathological threshold only the saturation point of UA (6.0 mg/dL in women and ≥7.0 mg/dL in men) [ [3] Li Q. Li X. Wang J. et al. Diagnosis and treatment for hyperuricemia and gout: a systematic review of clinical practice guidelines and consensus statements. BMJ Open. 2019; 9 Crossref Scopus (44) Google Scholar ], yet failing to identify a specific CV prevention cut-off [ [4] Visseren F.L.J. Mach F. Smulders Y.M. et al. 2021 ESC guidelines on cardiovascular disease prevention in clinical practice. Europe J Prev Cardiol. 2021; Crossref Google Scholar ]. This somewhat neglects UA predictive role in CV disease [ [5] Kaufman M. Guglin M. Uric acid in heart failure: a biomarker or therapeutic target?. Heart Fail Rev. 2013; 18: 177-186 Crossref PubMed Scopus (31) Google Scholar ]. In a large (n=22,714) Italian-population based observation cohort study, we have described how UA markedly impact all-cause and CV mortality starting from lower serum levels (respectively, 4.7 and 5.6 mg/dL) [ [2] Virdis A. Masi S. Casiglia E. et al. Identification of the uric acid thresholds predicting an increased total and cardiovascular mortality over 20 years. Hypertension. 2020; 75: 302-308 Crossref PubMed Scopus (62) Google Scholar ]. Several other observations have also found that UA enhances the CV mortality and morbidity risk stratification across the totality of the cardiometabolic spectrum using the same lower cut-offs [ [6] Pugliese N.R. Mengozzi A. Virdis A. et al. The importance of including uric acid in the definition of metabolic syndrome when assessing the mortality risk. Clin Res Cardiol. 2021; 110: 1073-1082 Crossref PubMed Scopus (7) Google Scholar , [7] Muiesan M.L. Salvetti M. Virdis A. et al. Serum uric acid, predicts heart failure in a large Italian cohort: search for a cut-off value the uric acid right for heart health study. J Hypertens. 2021; 39: 62-69 Crossref PubMed Scopus (12) Google Scholar ]. However, whilst in the current literature the relationship between UA in CV disease has been explored mainly in a chronic context (i.e. diabetes, hypertension, chronic kidney disease), little evidence is available to help us in defining whether the predictive power of UA holds true also for the acute setting, such as the acute coronary syndrome (ACS) [ [8] Maloberti A. Biolcati M. Ruzzenenti G. et al. The role of uric acid in acute and chronic coronary syndromes. J Clin Med. 2021; 10 Crossref Scopus (2) Google Scholar ].

Uric Acid Potential Role in Systemic Inflammation and Negative Symptoms After Acute Antipsychotic Treatment in Schizophrenia.

Uric acid (UA) has been shown to have neuroprotective or neurotoxic properties, in relation to specific tissues and diseases that have been studied. Previous studies provided contradictory results on the role of UA in schizophrenia as a neurodegenerative disorder. The aim of this brief report was an additional analysis of UA sera levels in different phases of schizophrenia. Here, 86 patients with first-episode psychosis (FEP) vs. 45 patients with schizophrenia in relapse (SC in relapse) vs. 35 healthy control subjects (HC) were studied before and 1 month after antipsychotic therapy. Further, we aimed to explore the possible correlation of UA with scores presenting clinical features and with serum concentrations of the proinflammatory cytokines interleukin (IL)-6 and IL-17. When comparing the data between all three groups, we did not find significant differences in UA levels, either before or after the applied therapy. Also, comparing sera concentrations of UA in every single group, the analysis did not reveal statistically significant differences between FEP patients, but statistically, a significant difference was found in SC in relapse before and after treatment (334.71 ± 116.84 vs. 289.37 ± 109.15 μmol/L, p = 0.05). Uric acid serum levels correlated with negative sub-score (p = 0.001, r = 0.306), general sub-score (p = 0.015, r = 0.236), and total PANSS score (p = 0.009, r = 0.3) after 1 month of therapy. We have established a statistically significant positive correlation between serum concentrations of UA and IL-6 in exacerbation (p = 0.01, r = 0.220) and with IL-17 after treatment and in the stabilization of psychosis (p = 0.01, r = 0.34), suggesting potential cascades in different phases of schizophrenia that potentiate inflammation.

Uric acid associated with acute heart failure presentation in Acute Coronary Syndrome patients

We focused on the role of Uric Acid (UA) as a possible determinant of Heart Failure (HF) related issues in Acute Coronary Syndromes (ACS) patients. Main outcomes were acute HF and cardiogenic shock at admission, secondary outcomes were the use of Non Invasive Ventilation (NIV) and the admission Left Ventricular Ejection Fraction (LVEF). We consecutively enrolled 1269 ACS patients admitted to the cardiological Intensive Care Unit of the Niguarda and San Paolo hospitals (Milan, Italy) from June 2016 to June 2019. Median age was 68 (first-third quartile 59–77) years and males were 970 (76%). All the evaluated outcomes occurred more frequently in the hyperuricemic subjects (UA higher than 6 mg/dL for females and 7 mg/dL for males, n = 292): acute HF 35.8 vs 11.1% (p < 0.0001), cardiogenic shock 10 vs 3.1% (p < 0.0001), NIV 24.1 vs 5.1% (p < 0.0001) and lower admission LVEF (42.9±12.8 vs 49.6±9.9, p < 0.0001). By multivariable analyses, UA was confirmed to be significantly associated with all the outcomes with the following Odds Ratio (OR): acute HF OR = 1.119; 95% CI 1.019;1.229; cardiogenic shock OR = 1.157; 95% CI 1.001;1.337; NIV use OR = 1.208; 95% CI 1.078;1.354; LVEF β = -0.999; 95% CI -1.413;-0.586. We found a significant association between UA and acute HF, cardiogenic shock, NIV use and LVEF. Due to the cross-sectional nature of our study no definite answer on the direction of these relationship can be drawn and further longitudinal study on UA changes over time during an ACS hospitalization are needed.

The role of uric acid in the development of cardiovascular diseases: from molecular mechanisms to clinical manifestations

The role of uric acid in the development of cardiovascular diseases: from molecular mechanisms to clinical manifestations

SERUM URIC ACID LEVELAMONG ACUTE CEREBROVASCULAR ACCIDENT PATIENTS IN MANIPUR

A large number of studies in the past give conicting results about the role of uric acid as a risk factor in patients with acute cerebrovascular accident (CVA). This study was carried out to measure the level of uric acid among acute cases of CVAand compare it with normal controls and also to nd its relationship with cerebrovascular risk factors. It was a cross sectional study, carried out on 60 patients with acute stroke, admitted in Regional Institute of Medical Sciences (RIMS) hospital , Imphal, from Nov 2018 to Oct 2020. Another 60 healthy individuals were taken as controls. Serum uric acid was measured by Enzymatic Colorimetric method. Mean age of the patients was 58.35+11.54 years. 54 patients were hypertensive, 28 (46.67%) had haemorrhagic stroke and 32 (53.33%) had ischemic stroke. Serum uric acid level was signicantly higher in CVA cases (7.64+2.01)mg/dL compared to controls (5.06+0.98)mg/dL. The level of uric acid was found to be signicantly higher in males (8.55+1.75)mg/dl compared to females (7.64+2.00)mg/dL. Maximum number of the patients had uric acid level &gt;8mg/dl. The level of uric acid was found to be more among the patients with ischemic stroke (7.97+1.87mg/dl) compared to haemorrhagic stroke (7.27+2.13mg/dl). A strong signicant positive correlation was observed with all the lipid parameters and a signicant negative correlation with HDL cholesterol. Increased serum uric acid may be considered as a risk factor of acute cerebrovascular accident.

348 Uric acid is associated with acute heart failure and cardiogenic shock at presentation in acute coronary syndrome patients

Abstract Aims we focused on the role of Uric Acid (UA) as a possible determinant of Heart Failure (HF) related issues in Acute Coronary Syndromes (ACS) patients. Main outcome were acute HF and cardiogenic shock at admission, secondary outcomes were the need of Non Invasive Ventilation (NIV) use and the admission Left Ventricular Ejection Fraction (LVEF). Methods and results we consecutively enrolled 1269 ACS patients admitted to the cardiological Intensive Care Unit of the Niguarda and San Paolo hospitals (Milan, Italy) from June 2016 to June 2019. Hyperuricaemia was defined as a value higher than 6 mg/dl for females and 7 mg/dl for males. All the evaluated outcomes occurred more frequently in the hyperuricemic subjects (n = 292): acute HF 35.8 vs. 11.1% (P &amp;lt; 0.0001), cardiogenic shock 10 vs. 3.1% (P &amp;lt; 0.0001), NIV 24.1 vs. 5.1% (P &amp;lt; 0.0001) with lower admission LVEF (42.9 ± 12.8 vs. 49.6 ± 9.9, P &amp;lt; 0.0001). By multivariable analyses, UA was confirmed to be significantly associated with all the outcomes with the following odds ratio (OR): acute HF OR = 1.119; 95% CI: 1.019–1.229; cardiogenic shock OR = 1.157; 95% CI: 1.001–1.337; NIV use OR = 1.208; 95% CI: 1.078–1.354; LVEF β = −0.999; 95% CI: −1.413 to − 0.586. Conclusions The main result of our study was the finding of a significant association between UA and acute HF, cardiogenic shock, NIV use and LVEF. Due to the cross-sectional nature of our study no definite answer on the direction of these relationship can be drawn and further longitudinal study on UA changes over time during an ACS hospitalization are needed.

Human fetal membrane IL-1β production in response to bacterial components is mediated by uric-acid induced NLRP3 inflammasome activation

Inflammatory interleukin-1β (IL-1β) is an important mediator of preterm birth. IL-1β secretion is mediated by the inflammasome that processes pro-IL-1β into its active form. However the mechanisms involved at the level of the fetal membrane (FM) are not fully understood. This study sought to determine the FM compartment involved in IL-1β production in response to bacterial components and to evaluate the mechanism of inflammasome activation. Since IL-18 is also mediated by the inflammasome and IL-8 is a chemoattractant that contributes to neutrophil recruitment in chorioamnionitis, we also evaluated the production of these factors. A human explant system was used to evaluate the response of the chorion, amnion, and intact FMs to the bacterial components lipopolysaccharide (LPS), peptidoglycan (PGN), or muramyl dipeptide (MDP). The chorion was the major source of IL-1β and IL-8 production in response to LPS, PGN, and MDP. LPS, PGN, and MDP induced FM IL-1β and IL-18 secretion in a non-pyroptotic manner through activation of the NLRP3 inflammasome with contributions from ATP release through Pannexin-1, and ROS signaling. Since LPS, PGN, and MDP are not known to activate NLRP3 directly, the role of uric acid as a potential mediator was assessed. FMs produced elevated uric acid in response to LPS, PGN and MDP. FM IL-1β secretion was inhibited by allopurinol, which blocks uric acid production, for LPS and PGN, and to a lesser degree, MDP. These findings shed light on the mechanisms by which fetal membrane inflammation and subsequent preterm birth may arise.

C-reactive Protein, Free Fatty Acid, and Uric Acid as Predictors of Adverse Events after Endovascular Revascularization of Arterial Femoropopliteal Occlusion Lesions

This study aimed to investigate the relationship between pre-procedure high-sensitivity C-reactive protein (hsCRP), free fatty acid (FFA), and uric acid (UA) levels and post-procedure mortality and morbidity of endovascular revascularization of arterial femoropopliteal occlusion lesions. This was a retrospective review of clinical data retrieved from a prospectively held database in Peking Union Medical College Hospital. A total of 71 Patients who underwent endovascular treatment (EVT) for femoropopliteal occlusive disease between January 1, 2014 and November 1, 2017, were included in this study. Endpoints were defined as major adverse limb events (MALE; target vessel revascularization, amputation, or disease progression) and major adverse cardiovascular events (MACE; stroke, myocardial infarction, or all-cause death) during the entire follow-up period. Univariate and multivariate Cox proportional hazards regression models were used to evaluate the relationship of elevated biomarker levels (hsCRP, FFA and UA, measured by immunoturbidimetry assay, enzymatic assay and enzymatic assay, respectively) to MALE and MACE outcomes. Seventy-one patients (72 limbs) with sufficient follow-up information were included in the analysis. The mean age was 69.7 ± 8.6 years; 21.1% were female. The Rutherford class of target limbs were ≥ 3. The median follow-up was 36 (range 18-59 months). Univariate analyses revealed that patients with elevated hsCRP levels had an increased risk of MALE (hazard ratio [HR], 2.682; 95% confidence interval [CI], 1.281-5.617, P=0.009). High FFA levels were associated with an increased risk of MALE (HR, 2.658; 95% CI, 1.075-6.573; P=0.034). Multivariate analyses demonstrated that elevated hsCRP values (HR, 4.015; 95% CI, 1.628-10.551; P=0.003) and FFA value (HR, 3.034; 95% CI, 1.102-8.354; P=0.032) were both significantly associated with increased MALE. Elevated UA levels predicted MACE in the presence of confounders (HR, 11.446; 95% CI, 1.367-95.801 P=0.023). Pre-procedure hsCRP and FFA levels could serve as predictors of adverse events after EVT in patients with arterial femoropopliteal occlusive disease. The role of UA in MACE may warrant further investigation, because the correlation is not as powerful as the other two in the study.

Protective Effect of Uric Acid on ox-LDL-Induced HUVECs Injury via Keap1-Nrf2-ARE Pathway.

Uric acid is an effective antioxidant. Oxidized low-density lipoprotein (ox-LDL) is derived from circulating LDL and promotes atherosclerosis. The Keap1-Nrf2-ARE pathway is a key body pathway involved in protection against internal and external oxidative damages. The role of uric acid on vascular endothelial function damaged by ox-LDL, and its effect on the Keap1-Nrf2-ARE pathway has not been fully explored. HUVECs were treated with different concentrations of uric acid and ox-LDL to explore the effect of uric acid in vitro. Cell phenotype was determined by cytometry and Western blot. Nuclear translocation of Nrf2 was determined by immunofluorescence. Coimmunoprecipitation was used to determine the level of Nrf2 ubiquitination. A microfluidic device was used to mimic the vascular environment in the body, and the level of mRNA levels of inflammatory factors was determined by RT-PCR. The findings of this study show that suitable uric acid can significantly reduce endothelial damage caused by ox-LDL, such as oxidative stress, inflammation, and increased adhesion. In addition, uric acid reduced Nrf2 ubiquitination and increased nuclear translocation of Nrf2 protein, thus activating the Keap1-Nrf2-ARE pathway and playing a protective role. Interestingly, the effects of UA were significantly inhibited by administration of Brusatol, an inhibitor of Nrf2. In summary, suitable concentrations of uric acid can alleviate the oxidative stress level of endothelial cells through Nrf2 nuclear translocation and further protect cells from damage.

Type 2 diabetes mellitus and gout

Gout is the most common inflammatory arthritis in adults and has continued to increase in prevalence over the past decades. Gout is characterized by hyperuricemia with the obligatory crystallization of urates and an associated inflammatory reaction, as well as metabolic effects caused, among other things, by these processes. In particular, the diagnosis of gout is identified with a high risk of carbohydrate metabolism disorders, which is 2 times higher than the population risk: according to various sources, from 21 to 26% of patients with gout have type 2 diabetes mellitus (DM 2). However, the role of uric acid and urate-lowering drugs in its development in patients with gout remains controversial. The possibility of influencing the risk of developing diabetes mellitus type 2 of chronic inflammation, the activity of interleukin-1β and other pro-inflammatory cytokines, hyperuricemia, xanthioxidase and other factors associated with gout is discussed. It is possible that the level of uric acid is associated with diabetes and other metabolic diseases, causing pathophysiological changes not only through inflammation, but also oxidative stress, damage to the vascular endothelium. It is also suggested that gout and DM 2 may share genetic markers. The interrelation of violations of purine and carbohydrate metabolism prompts the search for drugs that have a simultaneous positive effect on purine and carbohydrate metabolism. However, it is not clear what the level of uric acid should be considered as a risk factor, there are conflicting data on the possibility of reducing the risk of developing diabetes with various anti-gout therapies.

The Role of Uric Acid in Acute and Chronic Coronary Syndromes.

Uric acid (UA) is the final product of the catabolism of endogenous and exogenous purine nucleotides. While its association with articular gout and kidney disease has been known for a long time, new data have demonstrated that UA is also related to cardiovascular (CV) diseases. UA has been identified as a significant determinant of many different outcomes, such as all-cause and CV mortality, and also of CV events (mainly Acute Coronary Syndromes (ACS) and even strokes). Furthermore, UA has been related to the development of Heart Failure, and to a higher mortality in decompensated patients, as well as to the onset of atrial fibrillation. After a brief introduction on the general role of UA in CV disorders, this review will be focused on UA’s relationship with CV outcomes, as well as on the specific features of patients with ACS and Chronic Coronary Syndrome. Finally, two issues which remain open will be discussed: the first is about the identification of a CV UA cut-off value, while the second concerns the possibility that the pharmacological reduction of UA is able to lower the incidence of CV events.

An environment wide association study on body mass index in adolescents using 2003-2004 and 2013-2014 NHANES data

BACKGROUND AND AIM: Excess weight is a global public health challenge affecting millions of people, including younger age groups. The human exposome concept presents a novel opportunity to comprehensively characterize all non-genetic disease determinants at particularly susceptible time windows. Our study aimed to describe the association between multiple lifestyle and nutritional exposures and body mass index (BMI) in adolescents using the exposome framework METHODS: We conducted an environment-wide association study using the U.S. National Health and Nutrition Examination Survey (NHANES) survey of 2003-2004 for discovery of associations between the study population characteristics and BMI and the 2013-2014 survey to replicate the analysis. We included non-diabetic and non-pregnant adolescents aged 12-18 years-old. We analyzed variables available in both survey rounds, with 20% of missing values in relation to BMI z-scores. We performed univariable and multivariable linear regression analysis adjusted for age, sex, race-ethnicity, education, smoking, and income to poverty ratio. RESULTS:A total of 1899 (18.4% overweight and 18.1% obese) and 1224 (18.5% overweight and 20.6% obese) participants were identified in the target study population of the discovery and replication dataset, respectively. Retained exposure factors included 63 dietary and 50 clinical variables. After correction of false-discovery rate (FDR), univariable regression identified 10 and 13 clinical variables in the discovery and replication dataset, respectively. Multivariable regression identified 4 clinical variables in discovery dataset (uric acid; alanine aminotransferase; gamma glutamyl transferase and triglycerides) of which only uric acid remained significant in the replication dataset after FDR correction. CONCLUSIONS:Associations between BMI and different nutritional and clinical factors were explored and identified in adolescents. Future studies are warranted to investigate the possible role of uric acid as an early-stage biomarker of increased BMI and associated pathologies among adolescents and to replicate these findings to other populations. KEYWORDS: exposome, environment-wide association study, biomarker

The Prognostic Value of Serum Uric Acid in St-Segment Elevation Myocardial Infarction

Background and Objective: Acute myocardial infarction is the leading cause of mortality and morbidity across the world. Acute myocardial infarction with ST-segment elevation has been considered a common cardiac emergency and has considerable morbidity and mortality. The role of uric acid (UA) in the mortality rate of ST-segment elevation myocardial infarction (STEMI) was examined in the present study. Materials and Methods: In this prospective study, 107 patients diagnosed with STEMI aged 18 years and older in the coronary care unit at Azadi Teaching Hospital, Duhok, Iraq from April 20, 2017 to December 20, 2017 were followed up for 1 month to determine the 30-day mortality in relation to serum UA level. Results: The mean age of patients was 55.27±13.59 years. The inferior type of STEMI was the most prevalent one among the patients (45.1%). Serum UA was not significantly different in both the groups (P &gt; 0.05). Conclusion: The study did not show UA as a risk factor for mortality in patients with STEMI.

MO227RELATIONSHIP BETWEEN KIDNEY DAMAGE AND COGNITIVE FUNCTIONS IN PATIENTS WITH GLOMERULOPATHIES

Abstract Background and Aims Mild Cognitive Impairment (MCI) has been found to be highly prevalent amongst patients with Chronic Kidney Disease (CKD). In this cohort, the prevalence of MCI was estimated to be between 30% and 63%. Mild cognitive impairment is an intermediate state between normal aging and dementia. An individual suffering from MCI has difficulty in remembering, sustaining attention, or decision making which can negatively affect their daily lives. The aim of this study was to verify the role of different glomerular diseases diagnosed by kidney biopsy on the MCI through a retrospective study. Method We recruited 45 patients with bioptic diagnosis of the following glomerular diseases: Focal Segmental Glomerulo Sclerosis (FSGS), minimal change disease (MCD), membranous glomerular disease (MG), IgA nephropathy. The renal function was analyzed using clinical variables, while Cognitive functions using the MoCA test. Patients were divided into two groups based on 24h proteinuria. Results The MoCA score was directly correlated to the uric acid levels (R=0.13; p=0.03). The MoCa score in the group with higher proteinuria levels was significantly lower than those of the group with lower proteinuria levels (p = 0.03). Finally, the MoCA score in subjects with FSGS or MCD is significantly higher compared the other groups (p&amp;lt;0.05). Conclusion Our data suggest that serum uric acid and proteinuria in glomerular diseases influence cognitive functions. Interestingly, uric acid plays a neuroprotective role, as low levels of uric acid reduce the MoCA score. This result agrees with previous observations of a protective role of uric acid on dopamine neurons. Conversely, the extent proteinuria seems to negatively affect cognitive functions, suggesting a role of the endothelial dysfunction. Finally, glomerulopathies with a lower degree of inflammation (FSGS, MCD) have minor impact on cognitive functions.

Serum uric acid is no more a by-stander for risk of cardiovascular diseases in metabolic syndrome: a prospective study

Background: Cardiovascular diseases have become the fastest growing health issue in India and worldwide. Population with metabolic syndrome is known to be pre-disposed to several chronic disorders along with higher risk of experiencing cardiovascular events. The role of uric acid as a cardiovascular risk factor in metabolic syndrome was not well studied in the literature, which made us to undertake the present study.Methods: All the patients aged between 18 to 75 years (both gender) who approached Madhavbaug cardiac care clinics located in Maharashtra, India for assessing risk of heart disease from January 2015 to January 2017 were screened. Risk factors for metabolic syndrome have been evaluated among the study population and categorised into metabolic syndrome positive (³3 risk factors) and negative groups (&lt;3 risk factors). Statistical analysis was done using SPSS software version: 21.0.Results: Our study includes 2294 subjects who met the inclusion and exclusion criteria. Males outnumbered the females and sex ratio was 2.89:1. Females had lower serum uric acid levels compared to males irrespective of metabolic component. Gender and serum uric acid levels (high and low) were used stratification of the subjects. Serum uric acid is an independent predictor of cardiovascular diseases with an Odds ratio of 1.13 (95% confidence interval).Conclusions: Serum uric acid level is one of the important predictor for cardiovascular risk in metabolic syndrome. Raised uric acid is not an innocent by-stander and one of the major contributors in development of cardiovascular diseases.