Target Uric Acid Research Articles

Investigation of resveratrol as a xanthine oxidase inhibitor: Mechanistic insights and therapeutic implications for gout and hyperuricemia.

Gout predominantly stems from hyperuricemia, precipitating the accumulation of urate crystals and consequent joint inflammation, swelling, and pain, thereby compromising the quality of life and presenting a formidable medical dilemma. Although conventional treatments like allopurinol and febuxostat target uric acid reduction via xanthine oxidase (XO) inhibition, they often entail adverse effects, prompting the exploration of safer alternatives. Resveratrol, a polyphenolic compound abundant in fruits and vegetables, has emerged as a potential XO inhibitor. However, its precise inhibitory mechanisms remain poorly understood. This study aims to comprehensively investigate resveratrol's XO inhibition through mechanistic insights, molecular docking simulations, animal model experiments, and biochemical analysis, contributing valuable insights to the development of novel therapeutics for hyperuricemia and gout.

The Impact of Uric Acid-Lowering Therapy on the Progression of Non-dialysis Chronic Kidney Disease: A Prospective Cohort Study.

Background Hyperuricemia treatment can positively influence the progression of chronic kidney disease (CKD). This study aimed to evaluate the impact of uric acid-lowering therapy on the progression of CKD after three months. Materials and methods A prospective cohort study was conducted on 126 patients with non-dialysis CKD in Can Tho Central General Hospital, Vietnam, from December 2018 to December 2019. Adopting a questionnaire survey method to collect information, including demographic characteristics, body mass index (BMI), personal history, previous medical history, diet, and use of drugs with the potential to affect the uric acid levels in the blood. Participants also underwent necessary tests, such as serum uric acid, serum creatinine, and blood lipids. Data were analyzed using SPSS software version 26.0(IBM Corp., Armonk, NY). Results The prevalence of hyperuricemia in patients with non-dialysis CKD was 77.8%, and the average serum uric acid was 494.21 ± 131.57 µmol/L. Patients with a high-purine diet were about 18.85 times as likely to have hyperuricemia as those with a low-purine diet (p < 0.001, OR = 18.85, 95%CI: 4.233-83.938). BMI, stages of CKD, and hypertension were associated with the hyperuricemia rate (p < 0.05). After three months of treatment, 46.2% of patients achieved the serum uric acid target, and the patient group combined allopurinol with changing diet had a higher rate than the patient group changing diet only (p = 0.02). There was a moderate inverse correlation between the difference in serum uric acid and the difference in estimated glomerular filtration rate (eGFR) after treatment (r = -0.5, p = 0.001). Conclusions The effective management of hyperuricemia by combining nonpharmacological (changing diet) and/or pharmacological (allopurinol) therapies may meaningfully improve the glomerular filtration rate in non-dialysis CKD patients with hyperuricemia.

Battle of the strategies: diet versus drug therapy for gout

The best results in combating gout are achieved through a combination of diet and drug therapy. Urate-lowering therapy, which includes febuxostat, has been shown to be more effective and convenient than diet when it comes to achieving and maintaining target uric acid (UA) levels in gout patients. Febuxostat, a xanthine oxidase inhibitor, helps to reduce UA levels in the blood by blocking its formation. This helps prevent the deposition of urate crystals in joints and tissues and reduces the frequency and severity of gout attacks. At the same time, a diet of low purine foods may also have some effect on UA levels. Diet can improve the results of drug treatment by reducing the need for medications and minimizing the risk of side effects. However, without adequate drug therapy, diet will not produce the desired results. Therefore, febuxostat remains the preferred urate-lowering treatment option for gout, especially given its proven efficacy in these patients.

Urate-lowering therapy for gout: Difficulties in goal achieving the and ways to overcome

Urate-lowering therapy for gout: Difficulties in goal achieving the and ways to overcome

Spinal involvement in gout simulating spondyloarthritis (clinical case)

The article presents a case of the lumbar spine involvement in a 37-year-old patient with gout who was observed for several years with a diagnosis of spondyloarthritis. Spinal involvement in the context of gout was confirmed by dual-energy computed tomography. This is a relatively new method for the diagnosis of microcrystalline arthritis, which makes it possible to detect urate deposits in the atypical course of the disease, especially when the axial skeleton is affected. We demonstrate the advantages of the modern gout treatment strategy of achieving and maintaining target uric acid levels by prescribing appropriate doses of xanthine oxidase inhibitors (febuxostat at a dose of 120 mg/day) while preventing arthritis flares (low-dose colchicine).

Response to febuxostat according to clinical subtypes of hyperuricemia: a prospective cohort study in primary gout

BackgroundWhile xanthine oxidase inhibitors target uric acid production, renal urate underexcretion is the predominant subtypes in gout. This study was to compare treatment response to the XOI febuxostat in a gout cohort according to clinical subtypes of hyperuricemia.MethodsA prospective cohort study was conducted to compare the efficacy and safety of febuxostat (initially 20 mg daily, escalating to 40 mg daily if not at target) in 644 gout patients with the three major clinical subtypes for 12 weeks. Hyperuricemia was defined as the renal overload subtype, the renal underexcretion subtype, or the combined subtype based on UUE > or ≤ 600 mg/d/1.73 m2 and FEUA < or ≥ 5.5%. The primary endpoint was the rate of achieving serum urate (SU) < 6 mg/dL at week 12.ResultsFewer participants with combined subtype achieved the SU target, 45.5% compared with 64.8% with overload subtype (P = 0.007), and 56.6% with underexcretion subtype (P = 0.022). More participants with combined subtype (82%) had febuxostat escalated to 40 mg than those with overload (62%, P = 0.001) or underexcretion subtype (68%, P = 0.001). In all participants, combined subtype hyperuricemia (OR = 0.64, 95%CI 0.41–0.99, P = 0.048) and baseline SU (OR = 0.74, 95%CI 0.62–0.89, P = 0.001) were independently associated with lower rates of achieving SU target.ConclusionsPeople with combined subtype have a lower response to febuxostat, compared to those with either overload or underexcretion subtype. Assessment of hyperuricemia subtype may provide useful clinical data in predicting febuxostat response.

Realities of modern urate-reducing therapy for gout

Introduction. In the treatment of a patient with gout, it is important to achieve the target level of uric acid (UA) &lt; 360 μmol/l, which reduces the frequency of acute attacks of arthritis and improves the prognosis of comorbid diseases. Relief of acute gouty arthritis causes much less difficulty compared with the appointment of urate-l owering therapy (UST). The reasons for not achieving the target level of MC can be both objective and subjective.Aim. To analyze the objective and subjective components of the activity and effectiveness of UST in real outpatient practice.Material and methods. A cross- sectional study of 117 randomly selected outpatient records of patients diagnosed with gout. Mean age 58.6 ± 13.1, mean UA level 423.7 ± 122.4 μmol/L. Additionally, an anonymous survey of doctors and patients with gout was conducted on the issues of UST.Results. Patients with gout in the analyzed group were characterized by a high degree of polymorbidity: women and men, respectively, had arterial hypertension in 100 and 79%, type 2 diabetes mellitus in 39 and 23%, osteoarthritis in 73 and 57%. With inevitable polypharmacy, UST was prescribed in 37.6% of patients. Achievement of target levels of UA was registered in 23.8% of men and 39.4% of women. Failure to achieve the target sUA was associated with diuretics, elevated creatinine, and body mass index. Physicians were more than 70% active in prescribing UST, but knowledge of a single target UA level was demonstrated by 6 to 13%, depending on work experience, with an excessive assumption of UST use during an acute gout attack (19 to 36.5%). Conclusion. All components of the diagnostic and therapeutic process of curing a gouty patient need to be improved.

Achievement of serum uric acid target by rheumatology clinic pharmacists compared with primary care providers in patients with gout

BackgroundThe American College of Rheumatology strongly recommends a treat-to-target management strategy to achieve and maintain serum uric acid (sUA) less than 6 mg/dL to decrease risk of gouty flare recurrence and permanent joint damage. ObjectiveTo compare the effectiveness of rheumatology clinic pharmacists and primary care providers (PCPs) in achieving a target sUA goal in patients with gout. MethodsThis retrospective chart review included patients aged 18 years and older starting urate-lowering therapy (ULT) (allopurinol, febuxostat, or probenecid) for gout between January 1, 2015, and December 31, 2019. Exclusion criteria were ULT use within the previous 6 months, baseline sUA less than 6 mg/dL, and death within 12 months of starting ULT. From ULT initiation, data were collected until sUA less than 6 mg/dL was achieved or a maximum of 12 months. The primary outcome was the percentage of patients who achieved sUA less than 6 mg/dL. Key secondary outcomes were percent reduction in sUA and time to sUA target achievement. ResultsOf 62 patients included in each group, 75.8% of patients in the pharmacist cohort versus 30.6% of patients in the PCP cohort achieved target sUA less than 6 mg/dL (odds ratio 7.09, 95% confidence interval 3.28–16.11, P < 0.001). Patients in the pharmacist-managed group also achieved a greater reduction in mean sUA (−36.7% vs. −26.9% respectively, P = 0.001). Among patients achieving target sUA, median time to target was similar at 92 and 86 days, respectively, despite significantly lower initial mean allopurinol doses in the pharmacist-managed group (102 mg/d vs. 145 mg/d, P < 0.001). ConclusionThe odds of achieving target sUA within 12 months were 7 times higher if gout was managed by a rheumatology clinic pharmacist as compared with a PCP. This study suggests the need for prescriber education and supports expansion of pharmacist-led gout management to primary care settings.

The use of febuxostat in comorbid patients with gout in real clinical practice: own data

Objective: to evaluate the efficacy and safety of febuxostat (Azuriks®) in the treatment of patients with gout and concomitant diseases.Patients and methods. An observational, open-label, single-centre study of the results of febuxostat use in 85 gout patients with insufficient prior allopurinol efficacy or its intolerance. The median age of patients was 56.2 [49; 59] years, among them 83.5% were men. All patients had comorbid diseases, mainly cardiovascular pathology (76.5%) and chronic kidney disease (60%). The achievement of target values of uric acid (UA) during 4 months of urate-lowering therapy and its safety were assessed.Results and discussion. After 4 months of therapy with febuxostat, 25% of patients reached the target values of UA. Exacerbations at an early stage of the use of urate-lowering therapy were rare and were characterized by a lesser severity of the articular syndrome. Normalization of purine metabolism was accompanied by a decrease in the laboratory activity index (CRP level) to values corresponding to the interictal period of gout. Febuxostat was well tolerated.Conclusion. According to the data obtained, in patients with gout and concomitant diseases, febuxostat allows reaching target UA values in a short time without dose titration, while a high safety profile is noted.

Factors Affecting the Successful Treatment in Gouty Arthritis Patients at Nongkhai Hospital

Background: Gout is the most common inflammatory arthritis worldwide, with a prevalence ranging from less than 1% to 6.8% and an incidence of 0.58 to 2.89 per 1,000 cases per year, depending on the study. However, there are still problems in terms of diagnosis and treatment. Objective: To evaluate 1) the factors affecting the successful treatment in gouty arthritis patients, 2) the prevalence, patients’ characteristics, and factors associated with gouty arthritis, and 3) the problems of the diagnosis and treatment of gouty arthritis patients at Nongkhai Hospital, Thailand. Materials and Methods: The medical records of gouty arthritis patients treated in the outpatient department at Nongkhai Hospital between July 2010 and December 2020 were reviewed. Patients were divided into successfully treated group (STG) and unsuccessfully treated group (UTG) based on target uric acid level throughout the treatment. Factors affecting the successful treatment including address, nationality, age, gender, body mass index (BMI), duration of disease, presence of tophi, alcoholic intake, medical illness, medications, duration of treatment, physicians’ specialties, uric acid levels, glomerular filtration rate (GFR), alanine aminotransferase (ALT) before and after treatment, history of drugs discontinuation, and follow up were explored. Results: Of the 804 patients, 74.3% and 70.3% of patients achieved target uric acid level at one year and throughout treatment, respectively. Factors affecting the successful treatment were GFR before treatment of 60 or more mL/minute/1.73 m² (p=0.001), absence of tophi (p=0.023), and physicians’ specialties (p=0.001). Conclusion: The improvement of the physician’s education and treatment, close monitoring of patients with tophi, and GFR before treatment will increase the success of treatment and reduce complications. Keywords: Gout; Gouty arthritis; Tophi; Hyperuricemia; Outcome; Treatment; Predictor

Бессимптомная гиперурикемия и рентгенологическое прогрессирование ревматоидного артрита

Background: clinical and radiological studies on this issue remain unknown, despite the existing pathomorphological prerequisites, indicating the mutually potentiative effect of hyperuricemia (HU) on the radiographic progression (RP) in rheumatoid arthritis (RA). Aim: to study the association between the HU, the activity of RA, RP and the possibilities of their correction. Patients and Methods: among 967 patients included in the St. Petersburg City Register of HU from January 2011 to October 2021, 232 patients with RA and HU (uric acid (UA) level &gt; 360 μmol/L) were selected, for which 232 patients of the comparison group with RA without HU were selected by random selection from the same register. A comparison of the demographic characteristics of patients (gender, age), their clinical, laboratory and radiological patterns and the ongoing treatment was conducted. Results: patients with RA and HU and without HU were comparable in age, gender, activity, disease course and the received baseline therapy. In patients with RA and HU, there was a higher (p=0.03) increase in the joint space narrowing (JSN) value of the feet. In patients with RA and HU, RP in all evaluated parameters (p&lt;0,001) exceeded RP in patients with RA without HU. The article reveales direct correlations in the JSN of the feet and hands with the UA level, UA clearance, UA daily excretion, daily protein loss, as well as blood glucose and cholesterol levels, despite the well-known risk factors for the RA progression (age, disease duration, positivity according to RF and CCPA, elevated ESR and CRP level). Patients with HU and RP only reached the target UA levels in 27% of cases when treated with allopurinol, while patients without RP reached the target level in 80% of cases. Conclusion: HU in patients with RA is associated with RP, which indicates the need for its timely detection and correction. KEYWORDS: rheumatoid arthritis, asymptomatic hyperuricemia, radiographic progression, urate-lowering therapy, allopurinol. FOR CITATION: Tsinserling A.Yu., Mazurov V.I., Gaydukova I.Z. et al. Asymptomatic hyperuricemia and radiographic progression of rheumatoid arthritis. Russian Medical Inquiry. 2022;6(8):470–479 (in Russ.). DOI: 10.32364/2587-6821-2022-6-8-470-479.

Association of the Q141K polymorphism of the ABCG2 gene with the effectiveness of urate-lowering therapy in patients with gout (a pilot study)

Achieving the target serum uric acid (UA) level is a priority in the treatment of gout.Objective: to study the relationship of the ABCG2 gene polymorphism (rs2231142) with the efficacy of allopurinol and febuxostat in patients with gout.Patients and methods. The study included 82 patients with gout over 18 years of age with serum UA level &gt;360 μmol/L who did not take uratelowering therapy.All patients were prescribed allopurinol 100 mg daily, followed by its titration until the target UA level was reached (&lt;360 μmol/L or &lt;300 μmol/L in patients with chronic tofus gout), up to a maximum of 900 mg/day, in patients with glomerular filtration rate &lt;60 ml/min/1.73 m2 – up to 300 mg/day. Patients who did not reach the target UA level when using allopurinol were prescribed febuxostat 80 mg/day, which, if necessary, was increased to 120 mg/day. Monitoring of each patient was continued until the target serum UA level was reached.All patients underwent genotyping of the C&gt;A polymorphism (rs2231142) of the ABCG2 gene. We compared the probability of achieving the target UA level, the mean values of a decrease in the serum UA level, and the mean doses of urate-lowering drugs in patients with different genotypes (CC, CA, AA) of the ABCG2 gene.Results and discussion. The target UA level in 45 (55%) of 82 patients was defined as &lt;300 μmol/L, in the remaining 37 – as &lt;360 μmol/L.In 26 patients, the dose of allopurinol did not exceed 300 mg/day. In 28 (34%) patients treated with allopurinol, the target UA level was achieved, in the remaining 54 (66%) patients, allopurinol was substituted by febuxostat, and in 22 (41%) of them the UA level decreased and was below the target.The CC genotype of the ABCG2 gene was detected in 51 (62%) patients, the CA genotype in 30 (37%) and the minor genotype AA in 1 (1%).The probability of achieving the target UA level during therapy with allopurinol in carriers of homozygous CC genotype and genotypes CA or AA did not differ: 17 (33%) and 11 (35%) cases, respectively, but patients with CA and AA genotypes required a significantly higher dose of allopurinol (365±102 mg/day) than patients with the CC genotype (290±85 mg/day), p=0.002. Of the 54 patients who took febuxostat and did not reach the target UA level, 30 (56%) had the CC genotype and 24 (44%) had the CA genotype, the probability of reaching the target UA level was also comparable (p=0.22).Conclusion. The probability of reaching the target serum UA level in patients with gout taking allopurinol is not associated with the C&gt;A polymorphism of the ABCG2 gene, but the presence of CA and AA genotypes is identified with a higher dose of the drug. The C&gt;A (rs2231142) polymorphism of the ABCG2 gene does not affect the ability to achieve the goal of therapy when using febuxostat in patients with allopurinol ineffectiveness.

Effect of Topiroxostat on Brain Natriuretic Peptide Level in Patients with Heart Failure with Preserved Ejection Fraction: A Pilot Study

Various optimal medical therapies have been established to treat heart failure (HF) with reduced ejection fraction (HFrEF). Both HFrEF and HF with preserved ejection fraction (HFpEF) are associated with poor outcomes. We investigated the effect of topiroxostat, an oral xanthine oxidoreductase inhibitor, for HFpEF patients with hyperuricemia or gout.In this nonrandomized, open-label, single-arm trial, we administered topiroxostat 40-160 mg/day to HFpEF patients with hyperuricemia or gout to achieve a target uric acid level of 6.0 mg/dL. The primary outcome was rate of change in log-transformed brain natriuretic peptide (BNP) level from baseline to 24 weeks after topiroxostat treatment. The secondary outcomes included amount of change in BNP level, uric acid evaluation values, and oxidative stress marker levels after 24 weeks of topiroxostat treatment. Thirty-six patients were enrolled; three were excluded before study initiation.Change in log-transformed BNP level was -3.4 ± 8.9% (p = 0.043) after 24 weeks of topiroxostat treatment. The rate of change for the decrease in BNP level was -18.0 (-57.7, 4.0 pg/mL; p = 0.041). Levels of uric acid and 8-hydroxy-2'-deoxyguanosine/creatinine, an oxidative stress marker, also significantly decreased (-2.8 ± 1.6 mg/dL, p < 0.001, and -2.3 ± 3.7 ng/mgCr, p = 0.009, respectively).BNP level was significantly lower in HFpEF patients with hyperuricemia or gout after topiroxostat administration; however, the rate of decrease was low. Further trials are needed to confirm our findings.

A Population Based Study of Liver Function amongst Adults with Hyperuricemia and Gout in the United States.

To examine the association between uric acid levels and liver enzyme functions amongst adults with hyperuricemia and gout in the United States. The National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2016 was used to study the research objective. Data were analyzed for descriptive statistics and for differences using the t test, Chi-square test and ANOVA. A regression analysis was performed to determine association between demographics and liver enzymes. A p value of <0.05 or <0.001 was considered statistically significant. A total of 14,946 adults (≥20 yrs.) were included in this study. Sample mean age was 49 ± 0.15 yrs., and 54% were female. Overall, 15% adults had elevated uric acid levels (≥6.8 mg/dL), men had significantly higher uric acid levels than women (6 mg/dL vs. 4.8 mg/dL). High uric acid levels were associated with more than two times higher odds of elevated ALT, AST and GGT (p < 0.001). Similarly, gender-based target uric acid values were associated with two-fold increased odds of GGT, over one-and-a-half fold higher odds of ALT and AST (p < 0.001). Regression analysis showed significant association between age, gender, race/ethnicity, body mass index, and hypertension and ALT, AST, ALP, total bilirubin and GGT (p < 0.001). Adults with hyperuricemia and gout are most likely to develop liver dysfunctions and suffer associated morbidities. Such patients need to be appropriately monitored and managed for their liver functions and to prevent associated morbidities.

PERBANDINGAN EFIKASI DAN KEAMANAN PENGGUNAAN FEBUXOSTAT DAN ALLOPURINOL PADA PASIEN GOUT

Febuxostat and allopurinol are xanthine oxidase inhibitors to reduce uric acid levels. The research aimed to determine the differences in efficacy and safety of using febuxostat and allopurinol for gout patients. This research was conducted using a narrative review method for articles obtained from the PubMed and Willey databases published in 2010-2021. From the article exploration, 5 articles were reviewed showing that the determination of drug efficacy was seen by monitoring the changes in uric acid levels for 6 months from the beginning of drug use. Febuxostat and allopurinol had good efficacy in achieving target uric acid levels &lt; 6 mg/dL, however, febuxostat was superior to allopurinol in usual doses. Febuxostat 80 mg had superior efficacy to febuxostat 40 mg, while febuxostat 40 mg had superior efficacy to allopurinol 300 mg (p &lt; 0.05). For safety, febuxostat and allopurinol possessed similar side effects in the form of upper respiratory tract infection, diarrhea, headache, nausea and vomiting.

Impact of urate-lowering therapy on quality of life indicators in patients with gout

Gout can have a significant impact on the quality of life (QoL) of patients.Objective: to assess the dynamics of QoL indicators and the possibility of achieving the target level of uric acid (UA) in patients with gout on febuxostat therapy, with ineffectiveness and / or contraindications to the allopurinol administration.Patients and methods. The prospective, single-center study included 80 patients with gout. The follow-up period was at least 6 months of allopurinol or febuxostat (Azurix®) therapy in doses required to achieve the target UA level. When urate-lowering therapy was initiated, allopurinol 100 mg per day was prescribed, followed by dose titration (up to maximum of 900 mg per day) until the target UA level was reached (&lt;360 μmol/L). Patients with ineffectiveness of allopurinol and / or adverse reactions (ADRs) were transferred to febuxostat 80–120 mg per day. To prevent arthritis attacks, all patients received low doses of non-steroidal anti-inflammatory drugs or colchicine 0.5 mg per day or glucocorticoids 7,5 mg per day (in prednisolone equivqlent). At the first and last visits, patients on febuxostat completed the SF-36 questionnaire.Results and discussion. After 6 months of follow-up, 70 (88%) patients received urate-lowering therapy, of whom 51 (73%) reached the target UA level. Allopurinol dosage titration required 26 patients, of whom 14 (54%) achieved the treatment goal. Due to the ineffectiveness of allopurinol, 32 patients were switched to febuxostat, which allowed to achieve normouricemia in 69% of cases. Fifteen (68%) of 22 patients who were initiated with febuxostat due to ADRs to allopurinol also achieved the target UA level. Patients who received febuxostat and reached the target UA level improved QoL indicators: role-physical functioning, bodily pain, general health, vitality and general physical well-being (p&lt;0.05 in all cases). Patients who did not reach the target UA level on febuxostat therapy improved such indicators as physical functioning, role-physical functioning, and bodily pain (p&lt;0.05 in all cases). High compliance was observed in 63% of patients, treated with febuxostat and in 36% of patients, treated with allopurinol.Conclusion. In patients with ineffectiveness or intolerance to allopurinol, in 69% of cases febuxostat allows to achieve the target UA level and improving QoL and complience.

Urate levels and clearance in renal patients under peritoneal dialysis

Hemodialysis adequately controls serum uric acid (UA) levels, making UA-lowering drugs unnecessary; scant data are available for peritoneal dialysis (PD). We analyzed blood, 24 h urine and dialysis fluid from twenty patients under PD, to assess UA levels and clearances, and factors associated with better performance and maintenance of target levels (<6mg/dL). Median serum UA was 5.4 mg/dL (p25–75 4.4–5.8), mainly achieved through peritoneal clearance (3.0 mL/min/1.73m2, 71.2% of total UA clearance); 75% of participants was on UA targets. Continuous cycling peritoneal dialysis showed highest UA clearance and target achievements. These findings may be of interest for end-stage renal patients with gout.

Comparison of the efficacy and safety of various anti-inflammatory drugs in urate-lowering therapy initiation in patients with gout (preliminary data)

Non-steroidal anti-inflammatory drugs (NSAIDs), colchicine and glucocorticoids (GC) are used to prevent arthritis attacks in gout, but data on their comparative effectiveness is lacking.Objective: to compare the efficacy and safety of various anti-inflammatory drugs at the start of treatment in patients with gout.Patients and methods. Of the 108 patients with gout, observed in the V.A. Nasonova Research Institute of Rheumatology, 97 (94%), mostly men, entered a single-center prospective study. The observation period was at least 24 weeks, patients received combined urate-lowering and prophylactic anti-inflammatory therapy unintermittingly. The control group included 12 patients in whom anti-inflammatory drugs were contraindicated. At the start of urate-lowering therapy, allopurinol 100 mg per day was prescribed, followed by dose titration until the target uric acid (UA) level of &lt; 360 μmol/L level was reached, in patients with severe tophus gout it was &lt; 300 μmol/L. The maximum dose of allopurinol was 900 mg per day; in patients with reduced glomerular filtration rate (&lt;60 ml/min/1.73m2 ) – 300 mg per day. For the prevention of arthritis attacks, the drug of choice was colchicine 0.5 mg per day, when contraindicated and/or poorly tolerated, NSAIDs were prescribed in the minimum effective dose. If there were any NSAIDs use restriction or intolerance – prednisone 7.5 mg per day was administered. The effectiveness of anti-inflammatory therapy (NSAIDs, colchicine or GC) was evaluated after 3 and 6 months which included analysis of the frequency of exacerbations and the duration of arthritis attacks, the intensity of pain according to the visual analogue scale (VAS) during a gout attack.Results and discussion. Of 97 patients with gout, 85 (88%) received anti-inflammatory therapy: NSAIDs – 16 (19%), colchicine – 60 (71%), GC – 9 (10%). In 65% of patients who were administered anti-inflammatory therapy, there were no recurrence of arthritis, whereas in 12 patients of the control group who did not receive this treatment, recurrence of arthritis was absent only in 25% of cases (p=0.008). After 3 and 6 months of follow-up, the duration of gout attacks and the intensity of joint pain according to the VAS for recurrent arthritis were significantly less (p&lt; 0.05 in both cases) in the treatment group (with any anti-inflammatory drug) than without treatment. Arthritis attacks were more likely to be absent when taking NSAIDs than when using colchicine and GC both after 3 (63%) and 6 (81%) months (p&lt; 0.05 in both cases). After 3 months of observation, the intensity of pain according to the VAS during the development of a gout attack was less for NSAIDs therapy than for colchicine and GC (p&lt; 0.05 in both cases), and after 6 months there was no difference between NSAIDs, colchicine and GC. Within first 3 months, there was no difference in the duration of arthritis attacks among anti-inflammatory drugs, whereas after 6 months duration of attacks was the smallest for NSAID therapy (p&lt; 0.05). Adverse reactions occurred only in NSAID and colchicine therapy in 2 and 5 patients, respectively. The patient's refusal to continue therapy without cause occurred in 13 (15%) cases, more often when taking colchicine.Conclusion. The proposed algorithm of anti-inflammatory drugs prescription for prevention of arthritis recurrence can reduce the risk of gout attacks development with good tolerance of the therapy. At the same time, better control of the frequency and duration of arthritis attacks, as well as the intensity of pain according to the VAS, is observed with the use of NSAIDs than with the use of colchicine and GC.

Paper Microfluidics and Tailored Gold Nanoparticles for Nonenzymatic, Colorimetric Multiplex Biomarker Detection.

The plasmonic properties of gold nanoparticles (AuNPs) are a promising tool to develop sensing alternatives to traditional, enzyme-catalyzed reactions. The need for sensing alternatives, especially in underdeveloped areas of the world, has given rise to the application of nonenzymatic sensing approaches paired with cellulosic substrates to biochemical analysis. Herein, we present three individual, low-step, wet-chemistry, colorimetric assays for three target biomarkers, namely, glucose, uric acid, and free cholesterol, relevant in diabetes control and their translation into paper-based assays and microfluidic platforms for multiplexed analysis. For glucose determination, an in situ AuNPs synthesis approach was applied into the developed μPAD, giving semiquantitative measures in the physiologically relevant range. For uric acid and cholesterol determination, modified AuNPs were used to functionalize paper with a gold-on-paper approach with the optical properties changing based on different aggregation degrees and hydrophobic properties of particles dependent on analyte concentration. These paper-based assays show sensitivity ranges and limits of detection compatible for target analyte level determination and detection limits comparable to those of similar enzymatic, colorimetric systems, relying only on plasmonic transduction without the need for enzymatic activity or other chromogenic substrates. The resulting paper-based assays were integrated into a single 3D, multiplex paper-based device using paper microfluidics, showing the capability for performing different colorimetric assays with distinct requirements in terms of sample flow and sample uptake in test zones using a combination of both horizontal and vertical flows inside the same device. The presented device allows for multiparametric, colorimetric measures of different metabolite levels from a single complex sample matrix drop using digital color analysis, showing the potential for development of low-cost, low-complexity tools for diagnostics toward the point-of-care.

Targeting Uric Acid Prevents Brain Injury and Anxiety in a Rat Model of Hemorrhagic Shock.

Secondary brain injury following hemorrhagic shock (HS) is a frequent complication in patients, even in the absence of direct brain trauma, leading to behavioral changes and more specifically anxiety and depression. Despite preclinical studies showing inflammation and apoptosis in the brain after HS, none have addressed the impact of circulating mediators. Our group demonstrated an increased uric acid (UA) circulation in rats following HS. Since UA is implicated in endothelial dysfunction and inflammatory response, we hypothesized UA could alter the blood-brain barrier (BBB) and impact the brain. Male Wistar rats were randomly assigned to: SHAM, HS (hemorrhagic shock) and HS + U (hemorrhagic shock + 1.5 mg/kg of uricase). The uricase intervention, specifically targeting UA, was administered during fluid resuscitation. It prevented BBB dysfunction (fluorescein sodium salt permeability and expression of intercellular adhesion molecule-1) following HS. As for neuroinflammation, all of the results obtained (MPO activity; Iba1 and GFAP expression) showed a significant increase after HS, also prevented by the uricase. The same pattern was observed after quantification of apoptosis (caspase-3 activity and TUNEL) and neurodegeneration (Fluoro-Jade). Finally, the forced swim, elevated plus maze, and social interaction tests detected anxiety-like behavior after HS, which was blunted in rats treated with the uricase. In conclusion, we have identified UA as a new circulatory inflammatory mediator, responsible for brain alterations and anxious behavior after HS in a murine model. The ability to target UA holds the potential of an adjunctive therapeutic solution to reduce brain dysfunction related to hemorrhagic shock in human.