Association of uric acid with body adiposity and biochemical parameters in kidney transplant patients.

BACKGROUND: Obesity and various biochemical parameters, including triglycerides, cholesterol, glucose, C-reactive protein, and estimated glomerular filtration rate, have been linked to elevated uric acid (UA) levels in populations with normal kidney function due to decreased UA excretion and/or increased UA synthesis. However, it remains unclear whether all these factors exhibit similar associations with UA levels in clinical populations characterized by compromised renal function, such as kidney transplant patients (KTPs). OBJECTIVE: To evaluate whether serum UA levels are associated with body adiposity and biochemical parameters in KTPs. METHODS: A cross-sectional study involving 113 KTPs was conducted. Body fat was estimated using bioelectrical impedance, and waist circumference was measured using an inelastic tape. Serum levels of UA, creatinine, glucose, triglycerides, total cholesterol, and its fractions were measured using the colorimetric method. C-reactive protein levels were assessed using the immunoturbidimetric method, and urea levels were determined via enzymatic kinetics. Glomerular filtration rate was estimated using the chronic kidney disease epidemiology collaboration equation. Linear regression analyses were employed to assess the association between serum UA levels and body adiposity as well as biochemical parameters, while adjusting for confounders. RESULTS: Serum UA levels exhibited a positive association with creatinine (ß = 0.402; p = 0.013) and urea (ß = 0.024; p = 0.001), while demonstrating an inverse association with estimated glomerular filtration rate (ß = -0.030; p < 0.001). However, serum UA levels were not significantly associated with fat mass (both in kilograms and as a percentage), waist circumference, triglycerides, C-reactive protein, glucose, HDL cholesterol, LDL cholesterol, VLDL cholesterol, or total cholesterol. CONCLUSION: Serum UA levels are only associated with biochemical parameters linked to renal function in KTPs. Consequently, in individuals with suboptimal renal function, such as KTPs, UA does not exhibit associations with other biochemical parameters and body adiposity, as commonly observed in non-renal disease populations.

Unveiling overlooked pathways: The uric acid catabolism genes in the human genome.

In hominids, including Homo sapiens, uric acid is the end product of purine catabolism. In contrast, other placental mammals further degrade uric acid to (S)-allantoin by enzymes such as urate oxidase (uricase), HIU hydrolase (HIUase), and OHCU decarboxylase. Some organisms, such as frogs and fish, hydrolyze (S)-allantoin to allantoate and eventually to (S)-ureidoglycolate and urea, while marine invertebrates convert urea to ammonium. In H. sapiens, mutations in the uricase gene led to a reduction in the selective pressure for maintaining the integrity of the genes encoding the other enzymes of the purine catabolism pathway, resulting in an accumulation of uric acid. The hyperuricemia resulting from this accumulation is associated with gout, cardiovascular disease, diabetes, and preeclampsia. Many commonly used drugs, such as aspirin, can also increase uric acid levels. Despite the apparent absence of these enzymes in H. sapiens, there appears to be production of transcripts for uricase (UOX), HIUase (URAHP), OHCU decarboxylase (URAD), and allantoicase (ALLC). While some URAHP transcripts are classified as long non-coding RNAs (lncRNAs), URAD and ALLC produce protein-coding transcripts. Given the presence of these transcripts in various tissues, we hypothesized that they may play a role in the regulation of purine catabolism and the pathogenesis of diseases associated with hyperuricemia. Here, we specifically investigate the unique aspects of purine catabolism in H. sapiens, the effects mutations of the uricase gene, and the potential regulatory role of the corresponding transcripts. These findings open new avenues for research and therapeutic approaches for the treatment of hyperuricemia and related diseases.

Electrochemical Determination of Uric Acid Using a Nanocomposite Electrode with Molybdenum Disulfide/Multiwalled Carbon Nanotubes (MoS2@MWCNT).

This paper presents an application for a molybdenum disulfide nanomaterial with multiwalled carbon nanotubes (MoS2@MWCNT/E) in a modified electrode substrate for the detection of uric acid (UA). The modified electrode generates a substantial three-fold increase in the anodic peak current for UA compared to the unmodified MWCNT electrode (MWCNT/E). The MoS2@MWCNT/E surface was characterized by cyclic voltammetry (CV), scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS) and electrochemical impedance spectroscopy (EIS). The achieved detection limit stood at 0.04 µmol/L, with a relative standard deviation (RSD) of 2.0% (n = 10). The method's accuracy, assessed through relative error and percent recovery, was validated using a urine standard solution spiked with known quantities of UA.

Assessing levels of uric acid and other cardiovascular markers in prehypertensive and hypertensive adults.

INTRODUCTION: Although some studies have reported the association between uric acid (UA) and hypertension, evidence on prehypertension is still lacking. Therefore, the objective of this study was to determine the levels of UA and other cardiovascular markers among prehypertensive and hypertensive patients and assess their risk for developing arterial hypertension. METHODS: 157 individuals were recruited: 67 normotensive, 23 pre-hypertensive and 67 hypertensive. Blood samples were collected to measure biochemical parameters and anthropometric measurements and blood pressure were evaluated. We calculated the product of lipid accumulation and the visceral adiposity index to assess cardiovascular risk. RESULTS: Our data showed an increase in UA levels in normotensives (4.9±1.3mg/dL), prehypertensives (5.2±1.3mg/dL) and hypertensives (5.9±1.6mg/dL) (p=0.004). We found a higher frequency of hyperuricemia in the hypertensive group (34.3%) than in the normotensive group (13.4%, p<0.05). Hypertensive volunteers had lower levels of HDL-C (p=0.004 and p=0.003) and higher body mass indexes (p<0.001 and p=0.007), glucose (p<0.001 and p=0.033), triglycerides (p=0.001 and p=0.005), visceral adiposity index (p<0.001 and p=0.002) and lipid accumulation product (p<0.001 and p=0.007) than normotensive and prehypertensive participants. We also observed that individuals with UA≥6.2mg/dL had an increased risk of hypertension of 4.77 (p=0.003) compared to individuals with levels≤4.3mg/dL. CONCLUSION: Our results showed that UA is associated with increased blood pressure and unfavorable changes in anthropometric and biochemical parameters, which represent risk factors for hypertension and cardiovascular diseases.

Using point-of-care devices to examine covariation among blood nutritional-physiological parameters and their relationships with poxvirus infection, habitat urbanization, and male plumage coloration in house finches (Haemorhous mexicanus).

The development of inexpensive and portable point-of-care devices for measuring nutritional physiological parameters from blood (e.g., glucose, ketones) has accelerated our understanding and assessment of real-time variation in human health, but these have infrequently been tested or implemented in wild animals, especially in relation to other key biological or fitness-related traits. Here we used point-of-care devices to measure blood levels of glucose, ketones, uric acid, and triglycerides in free-ranging house finches (Haemorhous mexicanus)-a common songbird in North America that has been well-studied in the context of urbanization, nutrition, health, and sexual selection-during winter and examined (1) repeatability of these methods for evaluating blood levels in these wild passerines, (2) intercorrelations among these measurements within individuals, (3) how blood nutritional-physiology metrics related to a bird's body condition, habitat of origin (urban vs. suburban), poxvirus infection, and sex; and (4) if the expression of male sexually selected plumage coloration was linked to any of the nutritional-physiological metrics. All blood-nutritional parameters were repeatable. Also, there was significant positive covariation between concentrations of circulating triglycerides and glucose and triglycerides and uric acid. Urban finches had higher blood glucose concentrations than suburban finches, and pox-infected individuals had lower blood triglyceride concentrations than uninfected ones. Last, redder males had higher blood glucose, but lower uric acid levels. These results demonstrate that point-of-care devices can be useful, inexpensive ways of measuring real-time variation in the nutritional physiology of wild birds.

Serum uric acid concentration is associated with lower glomerular filtration rate in children undergoing kidney transplantation.

BACKGROUND: The relationship between serum concentration of uric acid (UA) and chronic kidney disease is complex due to many confounding variables. There is currently debate over whether hyperuricemia acts as a marker of kidney disease or as an independent risk factor. OBJECTIVES: To test the impact of serum UA concentration on the estimated glomerular filtration rate (GFR) of children undergoing kidney transplantation. PATIENTS AND METHODS: Prospective longitudinal study of children and adolescents after kidney transplantation. We analyzed clinical, anthropometric, and laboratory data at pre-transplant and 1, 3, and 6 months after transplant. We developed models of repeated measures analysis, using the generalized estimating equations technique for the outcome evolution of the estimated GFR at 1, 3 and 6 months. High serum UA concentration at 1 and 3 months was modeled as the main exposure variable. RESULTS: We included 103 transplant patients. In a model adjusted for time, recipient sex and age, the occurrence of acute rejection episodes, and the estimated glomerular filtration at baseline, the trajectory of GFR exhibited an inverse relationship with UA (ß = -7.1, 95% CI: -11.5 to -2.6, p < .01). CONCLUSION: Serum UA increase was associated with lower graft function over time.

De-escalating treatment indications for patients who achieve metabolic goals.

INTRODUCTION: Robust evidence exists regarding initiation, intensification or modification of treatments. Recommendations to de-escalate therapy are lacking, specifically in diabetes. A successful treatment de-intensification reduces overtreatment, polypharmacy, and risk of adverse effects. OBJECTIVE: To encompass current recommendations for deprescribing common drugs and create a consensus among health professionals. METHODS: We reviewed four databases for deprescribing approaches published between 2010 and 2022. Articles were divided into different groups of drugs (for uric-acid, hypoglycemic, lipid-lowering, and psychotropic drugs). RESULTS: Hypoglycemic agents: strategies were limited to newer agents and insulin regimens for elderly individuals. Reducing insulin was associated with 1.1% reduction of A1c over time. SGLT2i and GLP-1RAs dose reduction depends on adverse events. Lipid-lowering agents: studies show that patients with very low cholesterol have fewer cardiovascular events without associated increased risk. Antihypertensive agents: Younger patients, lower systolic blood pressure, and few comorbidities are ideal characteristics for discontinuation. Uric acid therapy: we found no recommendation for dose de-escalation. Poor treatment adherence is associated with episodes of gout and deforming arthritis in the long term. CONCLUSION: Deprescribing hypoglycemic, statins, antihypertensives, and urate-lowering agents may be feasible in selected patients, but periodic surveillance is important. More evidence is necessary to support this decision entirely.

Adherence to the Dietary Approaches to Stop Hypertension (DASH) and Serum Urate Concentrations: A Longitudinal Analysis from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

BACKGROUND: Increased serum urate (SU) and hyperuricemia (HU) are associated with chronic noncommunicable diseases and mortality. SU concentrations are affected by several factors, including diet, and are expected to rise with age. We investigated whether the Dietary Approaches to Stop Hypertension (DASH) diet alter this trend. OBJECTIVE: The objective was to assess whether adherence to the DASH diet predicts a longitudinal change in SU concentrations and risk of HU in 8 y of follow-up. METHODS: Longitudinal analyses using baseline (2008-2010, aged 35-74 y), second (2012-2014), and third (2016-2018) visits data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). The inclusion criteria were having complete food frequency questionnaire (FFQ) and urinary sodium measurement, in addition to having SU measurement at the 1st visit and at least 1 of the 2 follow-up visits. For the HU incidence analyses, participants had also to be free from HU at baseline. The final samples included 12575 individuals for the SU change analyses and 10549 for the HU incidence analyses. Adherence to DASH diet was assessed as continuous value. HU was defined as SU>6.8 mg/dL and/or urate-lowering therapy use. Mixed-effect linear and Poisson regressions (incidence rate ratio [IRR] and 95% confidence interval [CI]) were used in the analyses, adjusted for confounders. RESULTS: The mean age was 51.4 (8.7) y, and 55.4% were females. SU means (standard deviation) were 5.4 (1.4) at 1st visit, 5.2 (1.4) at 2nd visit, and 5.1(1.3) mg/dL at 3rd visit. The HU incidence rate was 8.87 per 1000 person-y. Each additional point in adherence to the DASH diet accelerated SU decline (P< 0.01) and lowered the incidence of HU by 4.3% (IRR: 0.957; 95% CI: 0.938,0.977) in adjusted model. CONCLUSION: The present study findings reinforce the importance of encouraging the DASH diet as a healthy dietary pattern to control and reduce the SU concentrations and risk of HU.

Analysis of the prognostic value of uric acid on the efficacy of immunotherapy in patients with primary liver cancer.

PURPOSE: Uric acid (UA) plays a dual role as an antioxidant and a prooxidant in patients with malignant tumors; however, the relationship between serum UA and malignancy is currently unclear. This study aims to investigate the prognostic value of serum uric acid level before immunotherapy on the efficacy of primary liver cancer (PLC) immunotherapy, which might provide a basis for optimizing the comprehensive treatment scheme. METHODS: Patients with PLC who were admitted to the First Affiliated Hospital of Gannan Medical College from January 2019 to June 2022 and underwent immunotherapy were collected retrospectively. The difference between serum UA levels in patients with PLC, the correlation between serum UA levels, and the clinical characteristics of patients with PLC were analyzed using the chi-square test, and the survival was estimated using the Kaplan-Meier analysis. To further assess the prognostic significance of UA concentrations, univariate and multivariate Cox regression analyses were performed. RESULTS: Ninety-nine patients were included in this study cohort. The median follow-up was 7 months (range: 1-29 months), and 76 (76.8%) of the 99 patients with PLC died as of December 31, 2022. Serum UA concentrations ranged from 105 to 670 µmol/l, with a median of 269 µmol/l. The results showed that the serum UA level of patients with PLC was higher than that of healthy subjects (P < 0.001). After subgroup analyses, only male patients with liver cancer had higher serum UA levels than healthy men (P = 0.001). The results of the Kaplan-Meier analysis showed that higher UA levels were associated with poor overall survival (OS) (P = 0.005). In univariate analysis, the OS rate of patients with elevated serum UA levels was significantly lower than the cut-off value (hazard ratio [HR]: 3.191, 95% confidence interval [CI]: 1.456-6.993, P = 0.004), with a median survival time of 151 and 312 days in the high and low serum UA groups, respectively. The results of multivariate analysis showed that the UA level was an independent prognostic factor for immunotherapy in patients with PLC (HR: 3.131, 95% CI: 1.766-5.553, P < 0.001). CONCLUSIONS: The serum UA level is a reliable biomarker for predicting the prognosis of patients undergoing immunotherapy for PLC, and might provide a basis for the individualized treatment of these patients. Dynamic monitoring of the serum UA level may compensate for the deficiency of the current liver cancer staging system.

The potential relationship between uric acid and the recovery in sudden sensorineural hearing loss.

OBJECTIVE: Serum uric acid is proven to be associated with chronic hearing loss, but its effect on Sudden Sensorineural Hearing Loss (SSNHL) is unclear. This study aims to evaluate the prognostic values of serum uric acid levels in SSNHL patients. METHODS: The clinical records of SSNHL patients were retrospectively reviewed. Patients were divided into different groups based on hearing recovery and audiogram type, and uric acid levels were compared. Based on uric acid levels, patients were categorized into normouricemia and hyperuricemia groups, and clinical features and hearing recovery were evaluated. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: In total, 520 SSNHL patients were included in this study, including 226 females and 294 males. In female patients, 186 patients were included in the normouricemia group, and 40 patients were enrolled in the hyperuricemia group. Significant differences were observed in uric acid levels, Total Cholesterol (TC), rate of complete recovery, and slight recovery between the two groups. In male patients, 237 subjects were categorized into the normouricemia group, and 57 patients were included in the hyperuricemia group. The rate of complete recovery and slight recovery was lower in the hyperuricemia group compared to the normouricemia group. All patients were further divided into good recovery and poor recovery groups based on hearing outcomes. The uric acid levels, initial hearing threshold, rate of hyperuricemia, and TC were lower in the good recovery group than the poor recovery group both in female and male patients. Binary logistic regression results showed that uric acid levels, initial hearing threshold, and hyperuricemia were associated with hearing recovery. CONCLUSION: Hyperuricemia might be an independent risk factor for hearing recovery in SSNHL patients. Serum uric acid and initial hearing threshold possibly affected the hearing outcome in males and females with SSNHL. LEVEL OF EVIDENCE: Level 4.

Effects of copper nanoparticles on performance, muscle and bone characteristics and serum metabolites in broilers / Efeitos de nanopartículas de cobre no desempenho, características musculares e ósseas e metabólitos séricos em frangos de corte

Three hundred and twenty day old Hubbard broilers were randomly allocated to four treatments (8 replicates, 10 birds/pen) and were raised under standard management conditions. Birds in the first group served as control and were fed a corn based diet, while birds in the remaining three groups i.e.; A, B and C were fed with a basal diet supplemented with copper nanoparticles (CuNP) at 5, 10 and 15 mg /kg of diet respectively for 35 days. Supplementation of CuNP linearly increased (P≤0.05) body weight (BW), average daily weight gain (ADWG) and feed intake (FI) in broilers. Uric acid, glucose levels in blood and feed conversion ratio (FCR) reduced linearly (P≤0.05) with CuNP supplementation in diet. Supplementation of CuNP in the diet also linearly increased (P≤0.05) tibia weight, length, diameter, weight/length index (W/L) and Tibiotarsal index (TT index). Inclusion of CuNP in broilers diet linearly increased the measured parameters of muscle i.e.; pH, fiber diameter, fiber cross-sectional area, fascicle diameter, fascicle cross-sectional area (P≤0.05). Concentration of copper, iron, calcium and phosphorous in blood also increased line-arly (P ≤ 0.05) with CuNP supplementation. Overall, CuNP positively affected the growth performance, histological characteristics of muscles, bone strength and serum metabolites in broilers.

Frangos de corte Hubbard com 320 dias de idade foram alocados aleatoriamente em quatro tratamentos (8 repetições, 10 aves/curral) e foram criados em condições de manejo padrão. As aves do primeiro grupo serviram como controle e foram alimentadas com uma dieta à base de milho, enquanto as aves dos três grupos restantes, ou seja, A, B e C, foram alimentadas com dieta basal suplementada com nanopartículas de cobre (CuNP) a 5, 10 e 15 mg/kg de dieta, respectivamente, por 35 dias. A suplementação de CuNP aumentou linearmente (P ≤ 0,05) o peso corporal (PC), o ganho de peso médio diário (GPDA) e o consumo de ração (FI) em frangos de corte. O ácido úrico, os níveis de glicose no sangue e a conversão alimentar (TCF) reduziram linearmente (P ≤ 0,05) com a suplementação de CuNP na dieta. A suplementação de CuNP na dieta também aumentou linearmente (P ≤ 0,05) peso, comprimento, diâmetro, índice peso/comprimento (P/L) e índice tibiotársico (índice TT) da tíbia. A inclusão de CuNP na dieta de frangos de corte aumentou linearmente os parâmetros medidos de músculo, ou seja; pH, diâmetro da fibra, área da seção transversal da fibra, diâmetro do fascículo, área da seção transversal do fascículo (P ≤ 0,05). A concentração de cobre, ferro, cálcio e fósforo no sangue também aumentou linearmente (P ≤ 0,05) com a suplementação de CuNP. No geral, CuNP afetou positivamente o desempenho de crescimento, características histológicas dos músculos, resistência óssea e metabólitos séricos em frangos de corte.

Investigating artificial intelligence models for predicting joint pain from serum biochemistry

SUMMARY OBJECTIVE: The study used machine learning models to predict the clinical outcome with various attributes or when the models chose features based on their algorithms. METHODS: Patients who presented to an orthopedic outpatient department with joint swelling or myalgia were included in the study. A proforma collected clinical information on age, gender, uric acid, C-reactive protein, and complete blood count/liver function test/renal function test parameters. Machine learning decision models (Random Forest and Gradient Boosted) were evaluated with the selected features/attributes. To categorize input data into outputs of indications of joint discomfort, multilayer perceptron and radial basis function-neural networks were used. RESULTS: The random forest decision model outperformed with 97% accuracy and minimum errors to anticipate joint pain from input attributes. For predicted classifications, the multilayer perceptron fared better with an accuracy of 98% as compared to the radial basis function. Multilayer perceptron achieved the following normalized relevance: 100% (uric acid), 10.3% (creatinine), 9.8% (AST), 5.4% (lymphocytes), and 5% (C-reactive protein) for having joint pain. Uric acid has the highest normalized relevance for predicting joint pain. CONCLUSION: The earliest artificial intelligence-based detection of joint pain will aid in the prevention of more serious orthopedic complications.

The potential relationship between uric acid and the recovery in sudden sensorineural hearing loss

Abstract Objective Serum uric acid is proven to be associated with chronic hearing loss, but its effect on Sudden Sensorineural Hearing Loss (SSNHL) is unclear. This study aims to evaluate the prognostic values of serum uric acid levels in SSNHL patients. Methods The clinical records of SSNHL patients were retrospectively reviewed. Patients were divided into different groups based on hearing recovery and audiogram type, and uric acid levels were compared. Based on uric acid levels, patients were categorized into normouricemia and hyperuricemia groups, and clinical features and hearing recovery were evaluated. Univariate and multivariate analyses were performed to identify prognostic factors. Results In total, 520 SSNHL patients were included in this study, including 226 females and 294 males. In female patients, 186 patients were included in the normouricemia group, and 40 patients were enrolled in the hyperuricemia group. Significant differences were observed in uric acid levels, Total Cholesterol (TC), rate of complete recovery, and slight recovery between the two groups. In male patients, 237 subjects were categorized into the normouricemia group, and 57 patients were included in the hyperuricemia group. The rate of complete recovery and slight recovery was lower in the hyperuricemia group compared to the normouricemia group. All patients were further divided into good recovery and poor recovery groups based on hearing outcomes. The uric acid levels, initial hearing threshold, rate of hyperuricemia, and TC were lower in the good recovery group than the poor recovery group both in female and male patients. Binary logistic regression results showed that uric acid levels, initial hearing threshold, and hyperuricemia were associated with hearing recovery. Conclusion Hyperuricemia might be an independent risk factor for hearing recovery in SSNHL patients. Serum uric acid and initial hearing threshold possibly affected the hearing outcome in males and females with SSNHL. Level of evidence Level 4.

Autosomic Dominant Tubulo Interstitial Kidney Disease: Case Report of a New Variant of the UMOD Gene.

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a low-prevalence pathology mainly associated with pathogenic variants of the UMOD gene. It is characterized by the progressive deterioration of renal function, associated with hyperuricemia and accompanied by a family history of gout or hyperuricemia. Often, clinical variability and a lack of molecular testing results in diagnostic failure to determine the ADTKD-UMOD association. Case presentation: We describe the case of a 14-year-old male who presented to the nephrology service with hyperuricemia, renal ultrasonographic changes, and progression to chronic kidney disease in 4 years. He had a family history of hyperuricemia. A probable genetic disease with an autosomal dominant inheritance pattern was considered, confirmed by the presence of a probably pathogenic variant of the UMOD gene, not previously reported in the literature. Conclusion: The investigation of this case led to the identification of a new variant in the UMOD gene, broadening the spectrum of known variants for ADTKD-UMOD. In addition, in this case, a comprehensive anamnesis, that takes into account family history, was the key point to carry out genetic tests that confirmed the diagnosis suspicion. Directed Genetic tests are currently an essential diagnostic tool and should be performed as long as they are available and there is an indication to perform them.

Anti-Hyperuricemic, Anti-Arthritic, Hemolytic Activity and Therapeutic Safety of Glycoconjugated Triazole-Phthalimides.

Hyperuricemia, the metabolic alteration that leads to gout or gouty arthritis, is increasing worldwide. Glycoconjugated triazole-phthalimides show potent anti-inflammatory activity. The aim of this study was to evaluate the anti-hyperuricemia effect of glycoconjugated triazole-phthalimides. To develop hyperuricemia, groups of mice received orally potassium oxonate (250 mg/kg) for 7 days, and F2, F3 and F4 glycoconjugated triazole-phthalimides (20 mg/kg), allopurinol (300 mg/kg), and 1% carboxymethylcellulose; indomethacin (2 and 4 mg/kg) was the positive control for anti-arthritic effect. Genotoxic and mutagenic effects were evaluated by the comet and micronucleus assays, respectively. The hemolytic action of the compounds was evaluated. Phthalimides F2, F3 and F4 significantly reduced the levels of serum uric acid, creatinine and urea in hyperuricemic animals. In addition, the compounds were efficient in reducing protein denaturation in a dose-dependent manner. In an interesting way, the histopathological analysis of kidneys from groups treated with F2, F3 and F4 showed a glomerular architecture, with the Bowman's capsule and renal tubules having a normal appearance and without inflammatory changes. Also, F2 and F4 showed a small increase in micronuclei, indicating a low mutagenic effect, whilst by comet assay only, we could infer that F4 affected the frequency and damage index, thus indicating a very small genotoxic action. Similarly, the phthalimides showed a low degree of erythrocyte hemolysis (<3%). Our data demonstrate that the new glycoconjugate triazole-phthalimides have potential to treat hyperuricemia and its secondary complications, such as gouty arthritis, with a low to non-significant rate of erythrocytes hemolysis, genotoxicity and mutagenicity making these molecules strong candidates as pharmaceutical agents for treatment requiring uric-acid-lowering therapy.

Sugar, salt, immunity and the cause of primary hypertension.

Despite its discovery more than 150 years ago, the cause of primary hypertension remains unknown. Most studies suggest that hypertension involves genetic, congenital or acquired risk factors that result in a relative inability of the kidney to excrete salt (sodium chloride) in the kidneys. Here we review recent studies that suggest there may be two phases, with an initial phase driven by renal vasoconstriction that causes low-grade ischemia to the kidney, followed by the infiltration of immune cells that leads to a local autoimmune reaction that maintains the renal vasoconstriction. Evidence suggests that multiple mechanisms could trigger the initial renal vasoconstriction, but one way may involve fructose that is provided in the diet (such as from table sugar or high fructose corn syrup) or produced endogenously. The fructose metabolism increases intracellular uric acid, which recruits NADPH oxidase to the mitochondria while inhibiting AMP-activated protein kinase. A drop in intracellular ATP level occurs, triggering a survival response. Leptin levels rise, triggering activation of the sympathetic central nervous system, while vasopressin levels rise, causing vasoconstriction in its own right and stimulating aldosterone production via the vasopressin 1b receptor. Low-grade renal injury and autoimmune-mediated inflammation occur. High-salt diets can amplify this process by raising osmolality and triggering more fructose production. Thus, primary hypertension may result from the overactivation of a survival response triggered by fructose metabolism. Restricting salt and sugar and hydrating with ample water may be helpful in the prevention of primary hypertension.

Concurrence of hyperinsulinemia and hyperuricemia significantly augmented all-cause mortality.

BACKGROUND AND AIMS: Hyperinsulinemia and hyperuricemia are known to increase the risk of mortality due to certain complications, such as Type 2 Diabetes and cardiovascular disease. However, despite their common comorbidities, their combined effect has not been evaluated. The study's aim was to evaluate the combine effect of hyperinsulinemia and hyperuricemia on all-cause mortality. METHODS AND RESULTS: NHANES datasets (cycles 2003-2018) were examined. Differences between groups were evaluated using Rao-Scott Chi-square and General Linear Model for categorical and continuous data, respectively. Hazard Ratios (HR) were calculated using Cox regression with 95% confidence intervals (95%CI). There was significant difference (p < 0.05) in the mortality rate between the control group (2.3 ± 0.2%), the hyperinsulinemia only group (3.1 ± 0.3%), the hyperuricemia only group (4.0 ± 0.8%), and both conditions (5.1 ± 0.8%). Individually, when compared to the control group, there was a significant increase in mortality risk for hyperinsulinemia (HR: 1.50, 95%CI: 1.12-2.01, p = 0.007) and hyperuricemia (HR: 1.80, 95%CI:1.18-2.75, p = 0.006). However, when both conditions were present, there appeared an additive effect in the mortality risk (HR: 2.32, 95%CI: 1.66-3.25, p < 0.001). When stratified by BMI class, only normal weight participants presented with a significant risk (HR: 7.00, 95%CI: 2.50-20.30, p < 0.001). Also, when stratified by age, only participants older than 40 years presented a risk (HR: 2.22, 95%CI: 1.56-3.16, p < 0.001). CONCLUSION: Alone, hyperuricemia and hyperinsulinemia significantly increased the mortality rate; however, the combined presence of both pathologies was associated with a significantly augmented mortality rate. Normal weight participant or that were >40 years old had a greater risk for mortality.

Simultaneous Determination of Uric Acid and Caffeine by Flow Injection Using Multiple-Pulse Amperometry.

The present study reports the development and application of a flow injection analysis (FIA) system for the simultaneous determination of uric acid (UA) and caffeine (CAF) using cathodically pretreated boron-doped diamond electrode (CPT-BDD) and multiple-pulse amperometry (MPA). The electrochemical profiles of UA and CAF were analyzed via cyclic voltammetry in the potential range of 0.20-1.7 V using 0.10 mol L-1 H2SO4 solution as supporting electrolyte. Under optimized conditions, two oxidation peaks at potentials of 0.80 V (UA) and 1.4 V (CAF) were observed; the application of these potentials using multiple-pulse amperometry yielded concentration linear ranges of 5.0 × 10-8-2.2 × 10-5 mol L-1 (UA) and 5.0 × 10-8-1.9 × 10-5 mol L-1 (CAF) and limits of detection of 1.1 × 10-8 and 1.3 × 10-8 mol L-1 for UA and CAF, respectively. The proposed method exhibited good repeatability and stability, and no interference was detected in the electrochemical signals of UA and CAF in the presence of glucose, NaCl, KH2PO4, CaCl2, urea, Pb, Ni, and Cd. The application of the FIA-MPA method for the analysis of environmental samples resulted in recovery rates ranging between 98 and 104%. The results obtained showed that the BDD sensor exhibited a good analytical performance when applied for CAF and UA determination, especially when compared to other sensors reported in the literature.

Association between serum uric acid and muscle strength in older adults with or without gout diagnosis: NHANES 2011-2014.

BACKGROUND & AIMS: Increased oxidative stress seems to be one of the causes of muscle strength loss during aging. Uric acid (UA) is an important antioxidant that has been positively associated with muscle strength in older adults. However, UA is also a prerequisite for gout, which is a type of arthritis that increases inflammation. The association between UA and muscle strength in individuals with gout is unknown. The aim of the study was to associate muscle strength with UA in older adults with or without gout diagnosis. METHODS: The present study evaluated older adults aged from 60 to 80 years from National Health and Nutrition Examination Survey (NHANES) 2011-2012 and 2013-2014. A total of 2529 individuals (1249 men and 1280 women) were evaluated, with (n = 201) or without (n = 2328) gout diagnosis. Muscle strength was measured using a handgrip dynamometer. The combined grip strength (sum of highest values of both hands) was evaluated. Linear regression analysis was performed to evaluate the association between UA and strength adjusting for confounders. RESULTS: Evaluating the individuals without gout, UA was positively associated with muscle strength [(ß = 0.66 (CI = 0.08; 1.24); p = 0.028)]. However, this association was not significant in individuals with gout [(ß = 0.20 (CI = - 1.18; 1.58); p = 0.774)]. CONCLUSION: Serum UA is positively associated with handgrip strength only in older adults without gout diagnosis. These results suggest that the presence of gout may avoid a positive association between UA and muscle strength in older adults.