Assessment of the efficacy of alkaline water in conjunction with conventional medication for the treatment of chronic gouty arthritis: A randomized controlled study.

BACKGROUND: Chronic gouty arthritis, a prevalent metabolic disorder, has prompted interest in the role of diet and lifestyle in its management. This study examines alkaline water as a non-pharmacological adjunct to traditional medicine, hypothesizing its positive effects on uric acid levels and gout symptoms. METHODS: In this research, 400 chronic arthritis patients from Guangdong Hydropower Hospital (September 2021-September 2023) were randomly assigned to groups receiving varying concentrations of alkaline water alongside conventional Western medicine, or Western medicine alone. A 1-year follow-up involved assessments using visual analogue scales, joint swelling scores, functional assessment scales, and biochemical markers (serum uric acid, creatinine, urea nitrogen) for comprehensive evaluation. RESULTS: Pain relief: High-concentration alkaline water significantly reduced VAS pain scores posttreatment (P < .05). Joint swelling: Greatest improvement observed in high-concentration group (P < .001). Daily activity capability: Notable enhancements in daily activity scores in experimental groups (P < .05). Range of joint motion: All groups showed significant improvement posttreatment (P < .05). Inflammatory markers: Experimental groups experienced a notable decrease in C-reactive protein, especially in the low concentration group (P < .001). Erythrocyte sedimentation rate decreases were marginal and not statistically significant (P > .05). Interleukin-1ß and tumor necrosis factor-α levels significantly decreased, particularly in the low concentration group. Serum uric acid levels: Significant reduction in serum uric acid observed in all alkaline water groups (P < .05), contrasting with the control group. CONCLUSION: Alkaline water, particularly at high concentrations, effectively alleviated pain, reduced joint swelling, enhanced daily activities, and improved joint motion in chronic gouty arthritis treatment. It significantly reduced key inflammatory markers (C-reactive protein, interleukin-1ß, tumor necrosis factor-α) and serum uric acid levels, suggesting its potential as a valuable adjunct in gout management. The limited impact on erythrocyte sedimentation rate warrants further investigation.

Interaction-based screening, Monte Carlo Bayesian inference-based de novo design and in vitro verification of adenine-binding peptide.

One of the main reasons for hyperuricemia is high purine intake. The primary strategy for treating hyperuricemia is blocking the purine metabolism enzyme. However, by binding the purine bases directly, we suggested a unique therapeutic strategy that might interfere with purine metabolism. There have been numerous reports of extensive interactions between proteins and purine bases. Adenine, constituting numerous protein co-factors, can interact with the adenine-binding motif. Using Bayesian Inference and Markov chain Monte Carlo sampling, we created a novel adenine-binding peptide Ile-Tyr-Val-Thr based on the structure of the adenine-binding motifs. Ile-Tyr-Val-Thr generates a semi-pocket that can clip the adenine within, as demonstrated by docking. Then, using thermodynamic techniques, the interaction between Ile-Tyr-Val-Thr and adenine was confirmed. The KD value is 1.50e-5 (ΔH = -20.2 kJ/mol and ΔG = -27.6 kJ/mol), indicating the high affinity. In brief, the adenine-binding peptide Ile-Tyr-Val-Thr may help lower uric acid level by blocking the absorption of food-derived adenine.

Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease: the ALL-HEART RCT and economic evaluation.

Background: Allopurinol is a xanthine oxidase inhibitor that lowers serum uric acid and is used to prevent acute gout flares in patients with gout. Observational and small interventional studies have suggested beneficial cardiovascular effects of allopurinol. Objective: To determine whether allopurinol improves major cardiovascular outcomes in patients with ischaemic heart disease. Design: Prospective, randomised, open-label, blinded endpoint multicentre clinical trial. Setting: Four hundred and twenty-four UK primary care practices. Participants: Aged 60 years and over with ischaemic heart disease but no gout. Interventions: Participants were randomised (1 : 1) using a central web-based randomisation system to receive allopurinol up to 600 mg daily that was added to usual care or to continue usual care. Main outcome measures: The primary outcome was the composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary outcomes were non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, all-cause mortality, hospitalisation for heart failure, hospitalisation for acute coronary syndrome, coronary revascularisation, hospitalisation for acute coronary syndrome or coronary revascularisation, all cardiovascular hospitalisations, quality of life and cost-effectiveness. The hazard ratio (allopurinol vs. usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis. Results: From 7 February 2014 to 2 October 2017, 5937 participants were enrolled and randomised to the allopurinol arm (n = 2979) or the usual care arm (n = 2958). A total of 5721 randomised participants (2853 allopurinol; 2868 usual care) were included in the modified intention-to-treat analysis population (mean age 72.0 years; 75.5% male). There was no difference between the allopurinol and usual care arms in the primary endpoint, 314 (11.0%) participants in the allopurinol arm (2.47 events per 100 patient-years) and 325 (11.3%) in the usual care arm (2.37 events per 100 patient-years), hazard ratio 1.04 (95% confidence interval 0.89 to 1.21); p = 0.65. Two hundred and eighty-eight (10.1%) participants in the allopurinol arm and 303 (10.6%) participants in the usual care arm died, hazard ratio 1.02 (95% confidence interval 0.87 to 1.20); p = 0.77. The pre-specified health economic analysis plan was to perform a 'within trial' cost-utility analysis if there was no statistically significant difference in the primary endpoint, so NHS costs and quality-adjusted life-years were estimated over a 5-year period. The difference in costs between treatment arms was +£115 higher for allopurinol (95% confidence interval £17 to £210) with no difference in quality-adjusted life-years (95% confidence interval -0.061 to +0.060). We conclude that there is no evidence that allopurinol used in line with the study protocol is cost-effective. Limitations: The results may not be generalisable to younger populations, other ethnic groups or patients with more acute ischaemic heart disease. One thousand six hundred and thirty-seven participants (57.4%) in the allopurinol arm withdrew from randomised treatment, but an on-treatment analysis gave similar results to the main analysis. Conclusions: The ALL-HEART study showed that treatment with allopurinol 600 mg daily did not improve cardiovascular outcomes compared to usual care in patients with ischaemic heart disease. We conclude that allopurinol should not be recommended for the secondary prevention of cardiovascular events in patients with ischaemic heart disease but no gout. Future work: The effects of allopurinol on cardiovascular outcomes in patients with ischaemic heart disease and co-existing hyperuricaemia or clinical gout could be explored in future studies. Trial registration: This trial is registered as EU Clinical Trials Register (EudraCT 2013-003559-39) and ISRCTN (ISRCTN 32017426). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/36/41) and is published in full in Health Technology Assessment; Vol. 28, No. 18. See the NIHR Funding and Awards website for further award information.

The purpose of the ALL-HEART study was to determine whether giving allopurinol to people with ischaemic heart disease (also commonly known as coronary heart disease) would reduce their risk of having a heart attack, stroke or of dying from cardiovascular disease. Allopurinol is a medication usually given to patients with gout to prevent acute gout flares. It is not currently used to treat ischaemic heart disease. We randomly allocated people aged over 60 years with ischaemic heart disease to take up to 600 mg of allopurinol daily (in addition to their usual care) or to continue with their usual care. We then monitored participants for several years and recorded any major health events such as heart attacks, strokes and deaths. We obtained most of the follow-up data from centrally held electronic hospital admissions and death records, making the study easier for participants and more cost-efficient. We asked participants in both groups to complete questionnaires to assess their quality of life during the study. We also collected data to determine whether there was any economic benefit to the NHS of using allopurinol in patients with ischaemic heart disease. There was no difference in the risk of heart attacks, strokes or death from cardiovascular disease between the participants given allopurinol and those in the group continuing their usual care. We also found no difference in the risks of other cardiovascular events, deaths from any cause or quality-of-life measurements between the allopurinol and usual care groups. The results of the ALL-HEART study suggest that we should not recommend that allopurinol be given to people with ischaemic heart disease to prevent further cardiovascular events or deaths.

Sex differences in the association of the uric acid to high-density lipoprotein cholesterol ratio with coronary artery disease risk among Chinese nondialysis patients with CKD stages 3-5.

BACKGROUND AND AIMS: Evidence has indicated that serum uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) are positively and negatively associated with coronary artery disease (CAD). The UA to HDL-C ratio (UHR) has recently drawn attention as a new predictor for metabolic syndrome, inflammation and atherosclerosis. However, the association between the UHR and CAD in nondialysis chronic kidney disease (CKD) patients is still unclear. METHODS AND RESULTS: We retrospectively analysed 733 733 nondialysis patients with CKD stage 3-5 who received their first coronary artery angiography (CAG), including 510 participants with CAD. All laboratory indicators were collected within one week before CAG. The median UHR of CAD and non-CAD patients was 15.52% and 12.29%, respectively. In multivariate analysis, female patients with a high UHR were 4.7 times more at risk of CAD than those with a lower UHR. Meanwhile, the positive association of the UHR with the severity of coronary artery stenosis (CAS) persisted significantly in female CAD subjects but not in males. In addition, receiver operating characteristic (ROC) curves were constructed for CAD and severe CAS. The area under the curve (AUC) for the UHR was higher than that for UA and HDL-C alone in female patients [UHR (AUC): 0.715 for CAD and 0.716 for severe CAS]. CONCLUSIONS: An elevated UHR was independently related to an increased CAD risk and the severity of CAS in nondialysis female patients with CKD stage 3-5, and was more predictive of the onset of CAD and the severity of CAS than UA or HDL-C alone.

Trends in healthcare utilization by patients with gout: A cross-sectional study using Health Insurance Review and Assessment Service data.

This study aimed to analyze the distribution of gout patients and the utilization of healthcare services in South Korea to provide valuable recommendations to clinicians and policymakers. A cross-sectional study was conducted. Claims data from the Health Insurance Review and Assessment Service spanning 2010 to 2019 were utilized, and a sample of 69,680 patients was included in the study. The incidence of gout was observed to be high in male patients over the age of 40, with most patients receiving outpatient care for gout management. Nonsteroidal anti-inflammatory drugs and urate-lowering agents were the most frequently prescribed medications, with prescriptions for colchicine and febuxostat increasing among urate-lowering agents. Musculoskeletal disorders were found to be the most common comorbidities among gout patients. Although the total costs of gout management increased, there was no significant increase in cost per patient. This study provides insights into the current state of healthcare utilization for gout patients in South Korea and trends in the disease burden and use of medications. The findings have crucial implications for clinicians and policymakers involved in decision-making regarding the management and treatment of gout.

Assessment of Hounsfield Units and Factors Associated with Fragmentation of Renal Stones by Extracorporeal Shock Wave Lithotripsy: A Computerized Tomography Study.

The success rate of extracorporeal shock wave lithotripsy (ESWL) is influenced by various factors, including stone density, and is determined through computed tomography scans in terms of Hounsfield units (HU). MATERIALS AND METHODS: This retrospective single-center study was conducted in the King Fahad Hospital. Sixty-seven adult patients with renal and ureteric stones were selected randomly and enrolled in the study. Their ages ranged from 20 to 69 years. The patients were examined with non-contrast enhancement (NCCT) to assess the HU of their stones and were consequently treated with ESWL. RESULTS: Of the 67 patients, 37.3% had stones that were completely fragmented, while 62.7% had stones that were partially fragmented. The HU, location of the stone, multiplicity of the stone, and patient age were found to be significant factors contributing to stone fragility (p-values < 0.05). The HU data were found to have a positive significant linear correlation with serum calcium (r = 0.28, p-value = 0.036), while serum acid had a negative correlation (r = -0.55, p-value < 0.001). Thus, the probability of calcium-containing stone formation increases with increased HU. In contrast, uric acid stone formation likely develops with decreasing HU with serum uric acid. Renal stones in patients with diabetes mellitus and hypertension were not completely fragmented compared to those without clinical history. CONCLUSIONS: Mean HU, location of the stone, laterality, stone status, and the number of ESWL sessions are the most significant factors affecting stone fragility. CT attenuation values can predict the composition of stones from serum calcium and uric acid examinations. Hypertension and diabetes mellitus are risk factors for renal stone fragmentation.

Gout in Native Hawaiian Patients in Hawai'i: Clinical Characteristics and Disparities.

OBJECTIVE: The purpose of this study was to investigate differences in clinical characteristics and health care use of Native Hawaiian and White patients with gout. METHODS: We performed a retrospective chart review of Native Hawaiian and White patients with gout treated from 2011 to 2017 within a large health care system in Hawai'i. We compared demographic characteristics, clinical outcomes, and risk factors for gout. We used multivariable logistic regression to identify predictive factors of emergency department visits. RESULTS: We identified 270 Native Hawaiian patients with gout and 239 White patients with gout. The Native Hawaiian patients were younger on average (54.0 vs 64.0 years; P < 0.0001) and had an earlier onset of disease (50.0 vs 57.0 years; P < 0.0001). Native Hawaiian patients with gout had higher mean (7.58 vs 6.87 mg/dL; P < 0.0001) and maximum (10.30 vs 9.50 mg/dL; P < 0.0001) serum urate levels compared to White patients with gout. Native Hawaiian patients with gout also had a greater number of tophi (median 2.00 vs 1.00; P < 0.0001). Native Hawaiians patients with gout were 2.7 times more likely to have frequent (≥1) emergency department visits than White patients with gout. Native Hawaiian patients with gout were less likely to have a therapeutic serum urate ≤6.0 mg/dL and had lower rates of rheumatology specialty care. CONCLUSION: Native Hawaiian patients have a higher disease burden of gout, with earlier disease onset and more tophi. Native Hawaiian patients with gout are more likely to use emergency services for gout and have lower rates of rheumatology specialty care compared to White patients. Future studies are needed to promote culturally appropriate preventive care and management of gout in Native Hawaiians.

Soluble urate-induced effects on cytokine production in vitro - Assessment of methodologies and cell types.

BACKGROUND: Hyperuricemia has been shown to be an inducer of pro-inflammatory mediators by human primary monocytes. To study the deleterious effects of hyperuricemia, a reliable and stable in vitro model using soluble urate is needed. One recent report showed different urate-dissolving methods resulted in either pro-inflammatory or anti-inflammatory properties. The aim of this study was to compare the effect of two methods of dissolving urate on both primary human peripheral blood mononuclear cells (PBMCs) and THP-1 cells. The two methods tested were 'pre-warming' and 'dissolving with NaOH'. METHODS: Primary human PBMCs and THP-1 cells were exposed to urate solutions, prepared using the two methodologies: pre-warming and dissolving with NaOH. Afterwards, cells were stimulated with various stimuli, followed by the measurement of the inflammatory mediators IL-1ß, IL-6, IL-1Ra, TNF, IL-8, and MCP-1. RESULTS: In PBMCs, we observed an overall pro-inflammatory effect of urate, both in the pre-warming and the NaOH dissolving method. A similar pro-inflammatory effect was seen in THP-1 cells for both dissolving methods after restimulation. However, THP-1 cells exhibited pro-inflammatory profile with exposure to urate alone without restimulation. We did not find MSU crystals in our cellular assays. CONCLUSIONS: Overall, the urate dissolving methods do not have critical impact on its inflammatory properties. Soluble urate prepared using either of the two methods showed mostly pro-inflammatory effects on human primary PBMCs and monocytic cell line THP-1. However, human primary PBMCs and the THP-1 differ in their response to soluble urate without restimulation.

Comparison of clinical and economic evaluation between selected generic and original febuxostat tablets in Chinese gout patients with hyperuricemia: A real-world multicenter retrospective study.

Generic febuxostat tablets were listed in China's third-round centralized drug procurement program. However, there are no sufficient data available on the use of febuxostat in a real-world setting. This study aimed to compare the efficacy, safety, and cost of selected generic febuxostat with original febuxostat in primary gout and hyperuricemia. Medical records at 3 tertiary hospitals from January 2014 to February 2022 were retrospectively analyzed. Propensity score matching was used to balance the distribution of baseline characteristics. The proportion of patients achieving target serum uric acid (SUA) levels at 12 weeks, the percent changes from baseline in SUA, adverse drug reactions, and the cost of febuxostat therapy were assessed. A total of 221 patients were recruited and 57 pairs of patients were 1:1 matched in the 2 groups. There was no statistically significant difference in the proportion of patients achieving a target SUA levels below 300 µmol/L, the percent changes of SUA decreased from baseline, and the incidence of adverse drug reactions between the 2 groups (all P > .05). The daily febuxostat cost in the generic group were significantly lower than that in original group (P < .05). Based on the results of this study, the clinical efficacy of selected generic febuxostat is comparable to that of original febuxostat for gout with hyperuricemia. No serious adverse reactions were reported in the 2 groups, and generic febuxostat is more economical than the original febuxostat.

A facile, low-cost bimetallic iron-nickel MOF nanozyme-propelled ratiometric fluorescent sensor for highly sensitive and selective uric acid detection and its smartphone application.

As a kind of well-known disease biomarker, uric acid (UA) is closely associated with normal metabolism and health. Despite versatile nanozymes facilitating the analysis of UA, most previous works could only generate single-signal outputs with unsatisfactory detection performance. Exploring a novel ratiometric fluorescent UA sensor with high sensitivity, reliability and portable sensing ability based on facile, low-cost nanozymes is still challenging. Herein, we report the first metal-organic-framework (MOF) nanozyme-originated ratiometric fluorescent UA sensor based on Fe3Ni-MOF-NH2 propelled UA/uricase/o-phenylenediamine tandem catalytic reaction. Different from previous reports, the peroxidase-like property and fluorescence of Fe3Ni-MOF-NH2 were simultaneously employed. In the absence of UA, only the MOF's fluorescence at 430 nm (FI430) can be observed, while the addition of UA will initiate UA/uricase catalytic reaction, and the generated H2O2 could oxidize o-phenylenediamine into highly fluorescent 2,3-diaminophenazine (DAP) (emission at 565 nm, FI565) under the catalysis of the MOF nanozyme. Coincidently, MOF's fluorescence can be quenched by DAP via the inner filter effect, resulting in a low FI430 value and high FI565 value, respectively. Therefore, H2O2 and UA can be alternatively detected through monitoring the above contrary fluorescence changes. The limit of detection for UA is 24 nM, which is much lower than those in most previous works, and the lowest among nanozyme-based ratiometric fluorescent UA sensors reported to date. Moreover, the portable sensing of UA via smartphone-based RGB analysis was facilely achieved by virtue of the above nanozyme-propelled tandem catalytic system, and MOF nanozyme-based molecular contrary logic pairs were further implemented accordingly.

Assessment of atherosclerosis and endothelial dysfunction risk factors in patients with primary glomerulonephritis.

INTRODUCTION: Glomerulonephritis are the third cause of chronic kidney disease (CKD) requiring dialysis in Brazil. Mineral and bone disorder (MBD) is one of the complications of CKD and is already present in the early stages. Assessment of carotid intima-media thickness (CIMT) and flow-mediated vasodilatation (FMV) are non-invasive ways of assessing cardiovascular risk. HYPOTHESIS: Patients with primary glomerulonephritis (PG) have high prevalence of atherosclerosis and endothelial dysfunction, not fully explained by traditional risk factors, but probably influenced by the early onset of MBD. OBJECTIVE: To evaluate the main markers of atherosclerosis in patients with PG. METHOD: Clinical, observational, cross-sectional and controlled study. Patients with PG were included and those under 18 years of age, pregnants, those with less than three months of follow-up and those with secondary glomerulonephritis were excluded. Those who, at the time of exams collection, had proteinuria higher than 6 grams/24 hours and using prednisone at doses higher than 0.2 mg/kg/day were also excluded. RESULTS: 95 patients were included, 88 collected the exams, 1 was excluded and 23 did not undergo the ultrasound scan. Patients with PG had a higher mean CIMT compared to controls (0.66 versus 0.60), p = 0.003. After multivariate analysis, age and values for systolic blood pressure (SBP), FMV and GFR (p = 0.02); and FMV and serum uric acid (p = 0.048) remained statistically relevant. DISCUSSION AND CONCLUSION: The higher cardiovascular risk in patients with PG was not explained by early MBD. Randomized and multicentric clinical studies are necessary to better assess this hypothesis.

Songbirds avoid the oxidative stress costs of high blood glucose levels: a comparative study.

Chronically high blood glucose levels (hyperglycaemia) can compromise healthy ageing and lifespan at the individual level. Elevated oxidative stress can play a central role in hyperglycaemia-induced pathologies. Nevertheless, the lifespan of birds shows no species-level association with blood glucose. This suggests that the potential pathologies of high blood glucose levels can be avoided by adaptations in oxidative physiology at the macroevolutionary scale. However, this hypothesis remains unexplored. Here, we examined this hypothesis using comparative analyses controlled for phylogeny, allometry and fecundity based on data from 51 songbird species (681 individuals with blood glucose data and 1021 individuals with oxidative state data). We measured blood glucose at baseline and after stress stimulus and computed glucose stress reactivity as the magnitude of change between the two time points. We also measured three parameters of non-enzymatic antioxidants (uric acid, total antioxidants and glutathione) and a marker of oxidative lipid damage (malondialdehyde). We found no clear evidence for blood glucose concentration being correlated with either antioxidant or lipid damage levels at the macroevolutionary scale, as opposed to the hypothesis postulating that high blood glucose levels entail oxidative costs. The only exception was the moderate evidence for species with a stronger stress-induced increase in blood glucose concentration evolving moderately lower investment into antioxidant defence (uric acid and glutathione). Neither baseline nor stress-induced glucose levels were associated with oxidative physiology. Our findings support the hypothesis that birds evolved adaptations preventing the (glyc)oxidative costs of high blood glucose observed at the within-species level. Such adaptations may explain the decoupled evolution of glycaemia and lifespan in birds and possibly the paradoxical combination of long lifespan and high blood glucose levels relative to mammals.

The Role of Ultrasound Semi-Quantitative Scoring in the Diagnosis and Assessment of Gout and Hyperuricemia.

OBJECTIVES: To develop an ultrasound semi-quantitative scoring system for the diagnosis and evaluation of gout and hyperuricemia. METHODS: This study included 348 male patients: 81 patients with asymptomatic hyperuricemia, 182 patients with gout, and 85 patients with other arthritis. Clinical data were collected, ultrasound was detected, gout activity score was calculated to assess disease activity, and statistical analysis was performed. RESULTS: Monosodium urate crystal deposition and subclinical arthritis were detected in 17 patients with asymptomatic hyperuricemia, with lesions concentrated in the metatarsophalangeal joint, ankle and peroneus-longus and brevis at rate of 91.8%. Gout was significantly higher than non-gouty arthritis in crystal scores (sum scores of double contour, aggregates, and tophi), but not in inflammation scores (sum scores of synovial hypertrophy, power Doppler [PD] activity, and tenosynovitis) and bone erosion. The optimal cut-off score for the diagnosis of gout by the crystal score was 2. The sensitivity, specificity, and AUC were 95.4%, 97.1%, and .965, respectively. Gout flare had higher inflammation scores than intercritical gout, while bone erosion scores were lower than intercritical gout. The active gout patients had higher ultrasound scores of tophi, bone erosion, and PD activity than the remission group (P < .001). The sensitivity, specificity and area under the receiver operating characteristic curve (AUC) for the identification with high disease activity gout by ultrasound semi-quantitative composite score were 76.2%, 84.2%, and .812, respectively. CONCLUSION: Ultrasound helps early identification of patients at risk in asymptomatic hyperuricemia. Ultrasound semi-quantitative scoring allows for more objective and accurate assessment of gout lesions, correlates with disease activity, and helps in the diagnosis and assessment of gout.

[Value of C-peptide-based insulin resistance index for evaluating correlation between insulin resistance and serum uric acid level in individuals undergoing health examination].

OBJECTIVE: To investigate the value of C-peptide-based insulin resistance index in evaluating the correlation between insulin resistance and serum uric acid (Ua) level in subjects undergoing health examination. METHODS: The data of 46 017 subjects undergoing health examination were retrospectively collected from the Second Medical Center of PLA General Hospital from January, 2017 to December, 2021. The subjects were divided into Ua≤420 µmol/L group and Ua>420 µmol/L group for comparison of HOMA insulin resistance index (HOMA2-IR) and HOMA insulin resistance-C peptide (HOMA2 IR-CP). The correlations of HOMA2-IR and HOMA2 IR-CP with Ua level were analyzed using Pearson correlation analysis and linear regression analysis. Hierarchical interaction analysis was conducted to assess the differences in the association between insulin resistance index and Ua level in different subgroups. The ROC curve was used to evaluate the predictive ability of insulin resistance index for an increased Ua level. RESULTS: The levels of HOMA2-IR and HOMA2 IR-CP were significantly lower in Ua≤420 µmol/L group than in Ua>420 µmol/L group. Univariate Pearson correlation analysis showed a weak correlation of HOMA2-IR with Ua (r=0.262, P<0.001) and moderate correlation of HOMA2 IR-CP with Ua (r=0.409, P<0.001). Multivariate linear regression analysis, after adjustment for confounding factors, demonstrated that HOMA2-IR (R2=0.445, P<0.001) and HOMA2 IR-CP (R2=0.461, P<0.001) were both factors affecting Ua level. Hierarchical interaction analysis showed that the association of insulin resistance index with Ua level varied significantly with gender, age, and glucose metabolism (P<0.001). ROC curve showed that the areas under the curve predicted an increased Ua level by HOMA2-IR and HOMA2 IR-CP were 0.662 and 0.722, respectively. CONCLUSIONS: HOMA2 IR-CP is a more accurate indicator for assessing the correlation between insulin resistance and Ua level.

Safety Assessment and Hepatic-Renal Protection of Cajanus cajan (L.) Millsp. Root and Its Soy Isoflavone Contents.

Cajanus cajan (L.) Millsp., also known as pigeon pea, has roots that have exhibited much pharmacological potential. The present study was conducted to assess the safe dose of the ethanolic extract of C. cajan roots (EECR95) and to analyze the main soy isoflavones contents. In vitro, we investigated the mutagenicity and cytotoxic effect of EECR95 on Salmonella typhimurium-TA98 and TA100 (by Ames tests) and RAW 264.7, L-929, and HGF-1 cell lines (by MTT tests) for 24 h of incubation. We found no mutagenic or cytotoxic effects of EECR95. After administration of 0.2 or 1.0 g/kg bw of EECR95 to both male and female Wistar rats for 90 days, there were no significant adverse effects on the behaviors (body weight, water intake, and food intake), organ/tissue weights, or immunohistochemical staining, and the urine and hematological examinations of the rats were within normal ranges. EECR95 potentially decreases renal function markers in serum (serum uric acid, BUN, CRE, and GLU) or liver function markers (cholesterol, triglyceride, and glutamic-pyruvate-transaminase (GPT)). We also found that EECR95 contained five soy isoflavones (genistein, biochanin A, daidzein, genistin, and cajanol), which may be related to its hepatorenal protection. Based on the high dose (1.0 g/kg bw) of EECR95, a safe daily intake of EECR95 for human adults is estimated to be 972 mg/60 kg person/day.

Serum and 24-hour urinary tests cost-effectiveness in stone formers.

OBJECTIVE: To assess the routine serum and 24-hour urine tests proficiency in diagnosing the baseline metabolic abnormality of kidney stone formers. METHODS: This study analyzes the routine serum and 24-hour urine tests proficiency in diagnosing the baseline metabolic abnormality of kidney stone formers. The sensitivity and specificity, false positive, and negative results of the tests are extracted from diagnostic kits used in the laboratories of the target community. To accurately infer the results, a simulation based on 1000 people was used through 22 standard laboratory tests (Additional File 2), including calcium, oxalate, phosphate, uric acid, sulfate, potassium, sodium, citrate, and magnesium in 24-hour urine; and calcium, creatinine, Vit D, uric acid, and intact parathyroid hormone (PTH) in serum. The incremental cost-effectiveness ratio (ICER) was calculated and compared for each diagnostic test versus other diagnostic tests according to the incremental cost required for correct diagnoses of stone causes. RESULTS: Urinary uric acid, citrate, and serum potassium constitute the cost-effectiveness boundary curve in this study. This means that other diagnostic tests are not cost-effective compared to these three tests in terms of indexing at least one item of cost and effectiveness. The ICER index for each correct diagnosis with the urinary uric acid test was $ 1.25 per diagnosis, the most cost-effective test compared to serum potassium and urinary citrate. CONCLUSION: The simplified blood and 24-hour urine metabolic evaluation, including urinary uric acid, citrate, and serum potassium, constitute the cost-effectiveness boundary curve. The most cost-effective test was urinary uric acid measurement.

Assessment and prognostic value of serum uric acid and neuron-specific enolase on the efficacy of intravenous thrombolytic therapy in cerebral infarction.

Assessment and prognostic value of serum uric acid (SUA) and neuron-specific enolase (NSE) on the efficacy of intravenous thrombolytic therapy in cerebral infarction. A retrospective analysis was performed on clinical data of 159 patients with acute cerebral infarction who received rt-PA intravenous thrombolytic therapy from 2015 to 2020 and patients with an mRS>2 points were assigned to the poor prognosis group and with mRS≤2 to the good prognosis group. The receiver operating characteristic curve (ROC) was used to examine the prognostic value of SUA and NSE in intravenous thrombolytic therapy for acute cerebral infarction, and logistic regression analysis was utilized to elucidate the predictive features. SUA levels were adversely correlated with prognosis, whereas NSE was positively correlated with prognosis (r=0.465 and -0.501, P=0.000 and 0.000). The ROC curve showed that the predictive accuracy of SUA was 77.4% and of NSE was 71%. SUA≤337.5 mmol/l and NSE≥24.50 ng/ml are considered viable criteria to predict the curative effect and prognostic value of intravenous thrombolytic therapy for acute cerebral infarction. SUA and NSE demonstrate great potential to accurately predict the therapeutic effect and prognosis of intravenous thrombolytic therapy for acute cerebral infarction.

Assessment of the toxic effects of levetiracetam on biochemical, functional, and redox parameters of salivary glands in male Wistar rats.

Levetiracetam (LEV) is an anticonvulsant for epilepsy. The toxic effects of this medication in tissues have been associated with redox state imbalance, which can lead to salivary gland dysfunction. Therefore, the current work investigated the effects of LEV on the biochemical, functional, and redox parameters of the parotid and submandibular glands in rats. For this, male Wistar rats (Rattus norvegicus albinus) were randomly divided into 3 groups (n = 10/group): Control (0.9% saline solution), LEV100 (100 mg/kg), and LEV300 (300 mg/kg). After 21 consecutive days of intragastric gavage treatments, pilocarpine stimulated saliva secretion was collected for salivary biochemical analysis. The extracted salivary glands were utilized for histomorphometry and redox state analyses. Our results showed that LEV300 increased plasma hepatotoxicity markers and reduced salivary amylase activity and the acinar surface area of the parotid gland. Total oxidant capacity and oxidative damage to lipids and proteins were higher in the parotid gland, while total antioxidant capacity and uric acid levels were reduced in the submandibular gland of the LEV100 group compared to Control. On the other hand, total oxidant capacity, oxidative damage to lipids and proteins, total antioxidant capacity, and uric acid levels were lower in both salivary glands of the LEV300 group compared to Control. Superoxide dismutase and glutathione peroxidase activities were lower in the salivary glands of treated animals compared to Control. In conclusion our data suggest that treatment with LEV represents a potentially toxic agent, that contributes to drug-induced salivary gland dysfunction.

Analysis of appropriate duration of colchicine prophylaxis to maximize the persistence of xanthine oxidase inhibitors as the first-line urate-lowering therapy in patients with gout using the Korean Health Insurance Review and Assessment Service database.

INTRODUCTION: We investigated the appropriate duration of colchicine prophylaxis to maximize the persistence of xanthine oxidase inhibitors (XOIs) as first-line urate-lowering therapy (ULT) in patients with gout. This was a nationwide population-based retrospective cohort study using the Korean Health Insurance Review and Assessment database. METHODS: Patients with gout aged ≥20 years who were newly initiated on XOIs, such as allopurinol or febuxostat, from July 2015 to June 2017 and received these medications for ≥6 months were analyzed and followed up until June 2019. Persistence of XOIs was compared according to the 6-month duration of colchicine prophylaxis. For additional subgroup analysis, we also compared the persistence of XOIs according to the 3-month duration of colchicine prophylaxis. RESULTS: This study included 43 926 patients. The frequencies of patients with gout receiving colchicine prophylaxis for ≥6 months and ≥3 months were 6.3% and 7.6%, respectively. Allopurinol (65.2%) was prescribed more frequently than febuxostat (34.8%). During the study period, 23 475 patients (53.4%) stopped using XOIs. Colchicine prophylaxis for ≥6 months did not significantly reduce the risk of XOI discontinuation in multivariable Cox regression models. Colchicine prophylaxis for ≥3 months was significantly associated with a lower risk of non-persistence to XOIs after adjusting for confounding factors (hazard ratio = 0.95, p = .041). CONCLUSION: Our data suggest that at least 3 months of colchicine prophylaxis may be more appropriate than at least 6 months in terms of maximizing the persistence of XOIs in patients with gout.

Assessment of metabolic risk factors for nephrolithiasis in patients with autosomal dominant polycystic kidney disease: a cross-sectional study.

BACKGROUND: Nephrolithiasis is more common in autosomal dominant polycystic kidney disease (ADPKD) than in the normal population. We aimed to investigate the anatomical and metabolic factors that may be associated with nephrolithiasis in patients with ADPKD METHODS: In this cross-sectional study, a total of 180 participants were included. Eighty-five patients with ADPKD [42 patients with nephrolithiasis (PKD N +) and 43 without nephrolithiasis (PKD N -)] were recruited. Forty-seven nephrolithiasis patients without ADPKD (N) and 48 healthy controls (HC) were selected as control groups. 24-h urine collections were measured in all participants. 24-h urine citrate, calcium, urate, oxalate, magnesium and sodium, serum electrolytes, and eGFRs were compared. RESULTS: Total kidney volumes were not different between patients with PKD N + and PKD N -. Hypocitraturia was common in all patients with ADPKD (69.4%), and it was not different between PKD N + (76.2%) and PKD N- (62.8%). However, hypocitraturia was statistically higher in PKD N + and PKD N - than in N (38.3%) and HC (12.5%) (p<0.05). 24-h urine calcium, urate, and oxalate levels were similar between PKD N + and PKD N - CONCLUSIONS: Hypocitraturia was found to be significantly higher in patients with ADPKD than in healthy adults and other kidney stone patients.