Decreased Uric Acid Levels Research Articles

Lactobacillus paracasei 259 alleviates hyperuricemia in rats by decreasing uric acid and modulating the gut microbiota

Hyperuricemia (HUA) is a metabolic disease arising from abnormal purine metabolism. It contributes to an increased risk of kidney damage. The present study aimed to investigate the uric acid (UA)-lowering effects of Lactobacillus paracasei 259 isolated from yak yogurt and explore its underlying mechanisms. Our results revealed that L. paracasei 259 decreased the UA levels in rats and inhibited the serum activities of xanthine oxidase. In addition, L. paracasei 259 reduced the levels of pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6) in the kidney and altered the expressions of UA transporters (ABC transporter 2 (ABCG2), PDZ domain containing 1 (PDZK1), urate transporter 1 (URAT1), and sodium-phosphate cotransporter type 4 (NPT4)) to near normal levels. Moreover, it increased the abundance of beneficial bacteria in the gut and recovered the gut microbiota composition, promoting the production of short-chain fatty acids (SCFAs). These findings suggested that L. paracasei 259 can potentially be used to decrease UA levels, repair kidney damage, regulate gut microbiota, and alleviate HUA.

Uric acid and alterations of purine recycling disorders in Parkinson’s disease: a cross-sectional study

The relationship between reduced serum uric acid (UA) levels and Parkinson’s disease (PD), particularly purine metabolic pathways, is not fully understood. Our study compared serum and cerebrospinal fluid (CSF) levels of inosine, hypoxanthine, xanthine, and UA in PD patients and healthy controls. We analyzed 132 samples (serum, 45 PD, and 29 age- and sex-matched healthy controls; CSF, 39 PD, and 19 age- and sex-matched healthy controls) using liquid chromatography-tandem mass spectrometry. Results showed significantly lower serum and CSF UA levels in PD patients than in controls (p < 0.0001; effect size r = 0.5007 in serum, p = 0.0046; r = 0.3720 in CSF). Decreased serum hypoxanthine levels were observed (p = 0.0002; r = 0.4338) in PD patients compared to controls with decreased CSF inosine and hypoxanthine levels (p < 0.0001, r = 0.5396: p = 0.0276, r = 0.2893). A general linear model analysis indicated that the reduced UA levels were mainly due to external factors such as sex and weight in serum and age and weight in CSF unrelated to the purine metabolic pathway. Our findings highlight that decreased UA levels in PD are influenced by factors beyond purine metabolism, including external factors such as sex, weight, and age, emphasizing the need for further research into the underlying mechanisms and potential therapeutic approaches.

Food-derived bioactive peptides with anti-hyperuricemic activity: A comprehensive review

Hyperuricemia (HU) is a metabolic disorder caused by the overproduction or underexcretion of uric acid (UA) in the human body. Several approved drugs for the treatment of HU are available in the market; however, all these allopathic drugs exhibit multiple side effects. Therefore, the development of safe and effective anti-HU drugs is an urgent need. Natural compounds derived from foods and plants have the potential to decrease UA levels. Recently, food-derived bioactive peptides (FBPs) have gained attention as a functional ingredient owing to their biological activities. In the current review, we aim to explore the urate-lowering potential and the underlying mechanisms of FBPs. We found that FBPs mitigate HU by reducing blood UA levels through inhibiting key enzymes such as xanthine oxidase, increasing renal UA excretion, inhibiting renal UA reabsorption, increasing anti-oxidant activities, regulating inflammatory mediators, and addressing gut microbiota dysbiosis. In conclusion, FBPs exhibit strong potential to ameliorate HU.

Data mining-guided alleviation of hyperuricemia by Paeonia veitchii Lynch through inhibition of xanthine oxidase and regulation of renal urate transporters

BackgroundHyperuricemia (HUA) is a metabolic disease characterized by a high level of uric acid (UA). The extensive historical application of traditional Chinese medicine (TCM) offers a range of herbs and prescriptions used for the treatment of HUA-related disorders. However, the core herbs in the prescriptions and their mechanisms have not been sufficiently explained. PurposeOur current investigation aimed to estimate the anti-HUA effect and mechanisms of Paeonia veitchii Lynch, an herb with high use frequency identified from data mining of TCM prescriptions. MethodsPrescriptions for HUA/gout treatment were statistically analyzed through a data mining approach to determine the common nature and use frequency of their composition herbs. The chemical constituents of Paeonia veitchii extract (PVE) were analyzed by UPLC-QTOF-MS/MS, while its UA-lowering effect was further evaluated in adenosine-induced liver cells and potassium oxonate (PO) and hypoxanthine (HX)-induced HUA mice. ResultsA total of 225 prescriptions involving 246 herbs were sorted out. The properties, flavors and meridians of the appearing herbs were mainly cold, bitter and liver, respectively, while their efficacy was primarily concentrated on clearing heat and dispelling wind. Further usage frequency analysis yielded the top 20 most commonly used herbs, in which PVE presented significant inhibitory activity (IC50 = 131.33 µg/ml) against xanthine oxidase (XOD), and its constituents showed strong binding with XOD in a molecular docking study and further were experimentally validated through XOD enzymatic inhibition and surface plasmon resonance (SPR). PVE (50 to 200 μg/ml) dose-dependently decreased UA levels by inhibiting XOD expression and activity in BRL 3A liver cells. In HUA mice, oral administration of PVE exhibited a significant UA-lowering effect, which was attributed to the reduction of UA production by inhibiting XOD activity and expression, as well as the enhancement of UA excretion by regulating renal urate transporters (URAT1, GLUT9, OAT1 and ABCG2). Noticeably, all doses of PVE treatment did not cause any liver injury, and displayed a renal protective effect. ConclusionsOur results first comprehensively clarified the therapeutic effect and mechanisms of PVE against HUA through suppressing UA production and promoting UA excretion with hepatic and renal protection, suggesting that PVE could be a promising UA-lowering candidate with a desirable safety profile for the treatment of HUA and prevention of gout.

Comparing Refrigeration to Immediate Room Temperature Testing for Uric Acid Monitoring in Rasburicase-Treated Patients

Abstract Rasburicase (Rb) is a uric acid (UA) degrading enzyme important for treating tumor lysis syndrome. Rb retains activity at room temperature (RT), so specimens collected for UA-level monitoring require cooling protocols: collecting samples in pre-chilled tubes, transporting on ice, centrifuging at 4°C, and testing within 4 hours. In our laboratory, specimens are tested within ~45 minutes of collection. Our clinical study objective was to determine if we could ease these pre-analytical requirements to improve compliance while maintaining accuracy. 50 pairs of specimens were transported and stored either on ice or at RT. All were tested at 3 time points post-collection: immediately upon arrival to the laboratory (~45 minutes), 90 minutes, and 135 minutes. Linear regression analysis of iced versus RT specimens showed a high correlation with R2= 0.99 (p&amp;lt; .0001) and bias of -2.4%, which indicate no clinical differences observed in UA concentrations between 1-12 mg/dL, at the immediate testing time point. UA levels did not significantly decrease in the iced specimens at any time point. However, UA levels had decreased by &amp;gt;10% in 16 of the 50 RT specimens after 90 minutes. Linear regression analysis of specimens tested immediately on ice versus RT specimens tested after 135 minutes yielded an R2= 0.84 (p&amp;lt; .0001) and bias of -17.5%. The best model from a stepwise regression was composed of the number of binned Rb half-lives (0-2 or &amp;gt;2) that had passed since the patients’ Rb infusion (Rb half-life= 1080 minutes; p&amp;lt; .0001) and the Rb dose (3 mg versus 6 mg, p&amp;lt; .0001), which explained ~50% of the UA variation (R2= 0.48, p&amp;lt; .0001). Keeping Rb dose constant, RT specimens tested within 0-2 half-lives post-infusion had an additional 24% average decrease in UA concentration compared to those tested after &amp;gt;2 half-lives. Similarly, keeping Rb half-life constant, RT specimens from patients given a 6-mg dose had an 18% decrease in UA concentration compared to patients given a 3-mg dose. Using a total allowable error (TEA) of 17% as a threshold, 96%, 60%, and 38% of RT specimens tested within 0-2 half-lives were within TEA at the immediate (45-minute), 90-minute, and 135-minute time points, respectively. In contrast, 100%, 96%, and 88% of RT specimens tested after &amp;gt;2 half-lives were within TEA at the immediate (45-minute), 90-minute, and 135-minute time points, respectively. UA concentrations are not clinically different in RT or iced specimens, as long as tested within ~45 minutes post-collection. Specimens tested within 2 Rb half-lives post-infusion have significantly decreased UA levels if kept at RT for &amp;gt;90 minutes. Laboratories that can test UA levels rapidly after specimen collection may be able to validate alternative pre-analytical methods to transporting and testing on ice.

Probiotic Limosilactobacillus fermentum GR-3 ameliorates human hyperuricemia via degrading and promoting excretion of uric acid

SummaryProbiotics have demonstrated the potential to ameliorate hyperuricemia in animals, but their effectiveness and mechanism of action in humans has been understudied. A randomized, double-blinded, controlled research was conducted with 120 volunteers, who consume either a probiotic yogurt containing a UA-degrading strain Limosilactobacillus fermentum GR-3 or a conventional yogurt for 2 months, to investigate probiotic yogurt helped decrease uric acid levels in the at-risk human population. Serum UA levels showed that the probiotic yogurt caused a significant decrease than the consumption of conventional yogurt (26.2% ± 2.3% vs. 8.6% ± 1.1%), and contributed to the UA excretion in the feces and urine (7.4% ± 2.1% and 13.8% ± 3.4%, respectively, 1.9% ± 1.1% and 5.1% ± 2.2%, respectively). Metabolomics and microbial community analysis showed a positive correlation with enhanced anti-inflammation of the host. Our findings suggest an effective and economical therapeutic adjuvant in treating hyperuricemia.

Flavonoid fraction from chayote (Sechium edule (Jacq.) Sw) leaves reduced malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) in hyperuricemic rats

PurposeThis paper aims to study the effect of the flavonoid fraction of chayote (Sechium edule (Jacq.) Sw) leaves (FFCL) on uric acid (UA) levels, oxidative stress and inflammatory markers in hyperuricemia rats.Design/methodology/approachIn total, 30 Sprague–Dawley rats were divided randomly into 5 groups. A healthy control group was established. Hyperuricemia was induced by the administration of block broth and potassium oxonate for three weeks. FFCL at dosages of 50 and 100 mg/200 g BW/d or allopurinol at a dosage of 1.8 mg/200 g BW/d was given orally for 2 weeks. Statistical analysis was conducted to evaluate differences among groups before and after the intervention.FindingsTreatment with two different doses FFCL (50 and 100 mg/200 g BW/d) and one dose of allopurinol (1.8 mg/200 g BW/d) for 2 weeks significantly reduced UA from 8.04 ± 0.23 to 3.88 ± 0.10; 8.03 ± 0.18 to 2.87 ± 0.10; 8.23 ± 0.21 to 2.53 ± 0.19 (p < 0.05), respectively. The oxidative stress marker malondialdehyde levels were reduced (p = 0.001) from 9.68 ± 0.28 to 4.06 ± 0.58; 10.01 ± 0.23 to 2.12 ± 0.09; 9.88 ± 0.21 to 2.02 ± 0.17 (p = 0.001). The inflammatory marker tumor necrosis factor-α (TNF-α) levels were also reduced from 26.43 ± 0.87 to 12.20 ± 0.32; 27.38 ± 0.53 to 9.60 ± 0.53; 27.55 ± 0.68 to 8.83 ± 0.21 with p = 0.001. The 100 mg/200 g BW/d FFCL decreased UA levels, oxidative stress and inflammatory markers more extensively compared to 50 mg/200 g BW/d FFCL.Research limitations/implicationsThis study includes some limitations that may affect the generalizability of its findings. First, the flavonoid levels of FFCL were not measured. Second, other oxidative stress biomarkers (e.g. superoxide dismutase) and inflammatory biomarkers (e.g. IL-6) were not investigated. Finally, the experiments were conducted on the model animals over a relatively short period of time. Further research is needed to evaluate the effect in humans at chronic use.Practical implicationsChayote (Sechium edule (Jacq.) Sw) leaves are rich in flavonoids, especially apigenin and luteolin, which can improve oxidative stress and inflammation conditions caused by hyperuricemia.Social implicationsHyperuricemia is a risk factor for non-communicable diseases, mostly caused by oxidative stress and inflammation in the body due to high levels of UA, one of the treatment strategies is through diet modification.Originality/valueThe results of this investigation imply that the administration of the flavonoid fraction of chayote leaves has significant effects on UA and oxidative stress and inflammatory markers. Further research is necessary to confirm the results.

5'-Nucleotidase Plays a Key Role in Uric Acid Metabolism of Bombyx mori.

Uric acid (UA) is the end-product in the human purine metabolism pathway. The UA that accumulates in silkworm tissues is excreted as a nitrogen waste product. Here, we first validated that Bombyx mori has a homolog of the human gene that encodes the 5′-nucleotidase (5′N) involved in purine metabolism. The B. mori gene, Bm5′N, is located upstream of other genes involved in UA metabolism in the silkworm. Disruption of Bm5′N via the CRISPR/Cas9 system resulted in decreased UA levels in the silkworm epidermis and caused a translucent skin phenotype. When Bm5′N mutant silkworms were fed with the uric acid precursor inosine, the UA levels in the epidermis increased significantly. Furthermore, the metabolomic and transcriptomic analyses of Bm5′N mutants indicated that loss of the Bm5′N affected purine metabolism and the ABC transport pathway. Taken together, these results suggest that the UA pathway is conserved between the silkworm and humans and that the Bm5′N gene plays a crucial role in the uric acid metabolism of the silkworm. Thus, the silkworm may be a suitable model for the study of UA metabolism pathways relevant to human disease.

Efficacy and Safety of Two Comparable Single Low Doses of Rasburicase Followed By Allopurinol in Adult Patients with Acute Leukemia

BACKGROUND: Hyperuricemia is a major cause of tumor lysis syndrome (TLS) related acute kidney injury. Certain hematologic malignancies (acute leukemia, high-grade lymphoma) pose a high-risk for spontaneous and chemotherapy-induced TLS. Allopurinol, a xanthine oxidase inhibitor, can inhibit formation of new uric acid (UA), but it does not eliminate the already formed UA. Alternatively, urate oxidases like rasburicase (ELITEK®, Sanofi Genzyme) can markedly and rapidly decrease UA levels through oxidation of UA to allantoin and hydrogen peroxide. In a phase III trial, rasburicase therapy more rapidly controlled UA than allopurinol in adults with hyperuricemia or at high-risk for TLS. However, rasburicase is expensive, especially when used as per the manufacturer's recommended dosage of 0.2mg/kg/day for up to 5 days. Numerous reports have shown that lower, and even single, doses are effective in lowering UA levels.OBJECTIVES: To determine the efficacy and safety of two single low doses of rasburicase (1.5mg vs. 3mg) in adult patients with acute leukemia and elevated plasma uric acid ≥ 7.5mg/dL.METHODS: Patients ≥ 18 years treated inpatient for acute leukemia with UA ≥ 7.5 mg/dL and at risk for TLS were randomized to one of two treatment arms (ClinicalTrials.gov Identifier: NCT01564277). Patients received either rasburicase 1.5mg (Arm A) or rasburicase 3mg (Arm B) intravenously over 30 minutes on day 1 in an open-label and unblinded fashion. All patients received allopurinol 300mg daily on days 1-6 (dose reduced for reduced calculated creatinine clearance). Plasma samples for UA evaluation were collected at baseline, and at approximately 4, 24, 48, 72, 96, 120, 144 hours after the Day 1 dose of rasburicase. If UA > 7.5 mg/dL at 24 or 48 hours, then additional dose of rasburicase could be administered (1.5mg for Arm A, 3mg for Arm B). Primary endpoint was the response rate of obtaining UA ≤ 7.5mg/dL within 24 hrs of rasburicase treatment. Secondary endpoints included rate of patients that maintained UA ≤ 7.5 mg/dl on days 2-6, rate of patients who required additional rasburicase doses, rate of patients experiencing significant worsening of renal function, as well as safety of low single-dose rasburicase. Patients were followed for adverse events (AE; as defined in CTCAE version 4) for up to 30 days after last dose of rasburicase or resolution of drug-related AE.RESULTS: 24 patients were enrolled on this phase 2 study (12 on each arm; Table 1). 83% of patients in both arms achieved UA response by 24 hours (Table 2). Two pts in Arm A (baseline UA: 14.2 and 17.6 mg/dL) and three pts in Arm B (baseline UA: 15.3, 10.2, 11.9 mg/dL) were given one additional rasburicase dose. Only one pt (from Arm A) had UA > 7.5 mg/dL between days 2-6. None of the patients had doubling of their baseline serum creatinine or required hemodialysis support. Average decrease in UA was lower in Arm A as compared to Arm B (5.5 vs. 6.8 mg/dL). AE data from 21 pts showed that both low doses were overall well tolerated and most toxicities were unrelated to rasburicase. No patient deaths were attributed to rasburicase. An ad-hoc analysis showed significant rasburicase specific cost benefits using either of the low doses as compared to FDA approved dosage and other studied regimens (Table 3).CONCLUSIONS: Single low doses of rasburicase (1.5mg and 3mg) plus allopurinol are well tolerated and appear to be equally efficacious in decreasing UA levels in adult patients with leukemia at high risk for TLS. If baseline UA is elevated (>12 mg/dL), a 3mg or higher dose of rasburicase might be preferable. Preliminary cost analysis profiling favors the use of the low dose rasburicase. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

EFEKTIVITAS EKSTRAK ETANOL DAUN EFEKTIVITAS EKSTRAK ETANOL DAUN SIDAGURI (Sida rhombifolia L.) TERHADAP PENURUNAN KADAR ASAM URAT PADA TIKUS JANTAN GALUR WISTAR HIPERURISEMIA

Sidaguri leaves (Sida rhombifolia L.) Have been shown to contain flavonoid compounds, where they are efficacious as hyperuricemia. This study aims to determine effectiveness ethanol extract of sidaguri leaves as antihyperuricemia in white rats. The study was conducted using the method of potassium oxanate induction and measured using glucometers. 15 animals were divided into 5 groups, namely negative control, positive control, group I combination of ethanol extract of sidaguri leaves 50 mg / kg body weight, group II ethanol extract of sidaguri leaves 100 mg / kg body weight, group III ethanol extract of sidaguri leaves 200 mg / kg body weight for 5 hours. Examination of antihyperuricemia effects is done by comparing the uric acid levels value of the rats before and after treatment. The results of this study indicate that the three dose ethanol extract of sidaguri leaves provide an antihyperuricemia effect and based on one-way Anova, Tuckey and LSD data analysis, shows that the dose of 50 mg / kg body weight is effective as antihyperuricemia and does not have a significant difference (p&gt; 0.05). The conclusion of this study is that the dose is the most effective in decreases uric acid levels in white rats, which is a dose of 200 mg / kg body weight because it mostly decreased uric acid levels.

Oxidative stress and neuroinflammation should be both considered in the occurrence of fatigue and depression in multiple sclerosis.

Oxidative stress and neuroinflammation have a role in the pathogenesis of multiple sclerosis (MS) and in depression. Fatigue is the most disabling symptom in patients with MS and could also be a part of depressive symptomatology. In this study, we measured the serum levels of uric acid (UA) as a marker of oxidative stress and C-reactive protein (CRP) as an inflammatory marker, in 98 patients with MS in relapse and remitting phase of illness and 35 healthy subjects. Degree of depressive symptomatology and fatigue were assessed with Beck's Depression Inventory (BDI) and Fatigue Severity Scale (FSS). Further, we examined the possible correlation of these biomarkers with symptoms of depression and fatigue. Relapse and remitting MS had a lower serum UA levels than controls (236.97 ± 9.25µmol/L vs. 268.27 ± 0.09µmol/L vs. 314.82 ± 11.02µmol/L; p = 0.000), while sera levels of CRP were higher in relapse than remitting patients (4.46 ± 0.40mg/L vs. 1.01 ± 0.38mg/L; p = 0.000). Patients in relapse had higher BDI scores (15.68 ± 16.62 vs. 8.36 ± 7.10; p = 0.045). Decreased UA levels showed weak negative correlation with the presence of sadness and disturbed daily activities, higher CRP levels positively correlated with severe depression and the correlation between depression and fatigue was also observed (p < 0.05). It is possible that decreased UA levels lead to sadness, disturbed daily activities and severe disability. Every attack of CRP elevation in relapse could additionally precipitate the depression onset. The clinicians must pay special attention to early detection of fatigue because it could precede depression and improve further treatment.

Uric acid is an independent predictor of cardiac allograft vasculopathy after heart transplantation.

Cardiac allograft vasculopathy (CAV) is a major complication after heart transplantation (HT). Uric acid (UA) may play a role in CAV due to its role in stimulating T-cell-mediated immunity. Sirolimus is associated with CAV attenuation through a number of mechanisms, including immune-mediated effects. We aimed to determine whether UA is an independent predictor of CAV and whether conversion to sirolimus as primary immunosuppression modulates UA levels. We retrospectively analyzed a cohort of 224 patients who underwent HT between 2004 and 2015 and had serial coronary intravascular ultrasound (IVUS) studies. Serum UA levels were measured at baseline and last follow-up IVUS in all participants. CAV progression was assessed by measuring the change in plaque volume (ΔPV) and plaque index (ratio of plaque volume to vessel volume [ΔPI]) between last follow-up and baseline IVUS after correction for time of follow-up. Patients with high (≥7 mg/dl) compared with low (<7 mg/dl) UA had increased median ΔPV (0.33 [interquartile range 0.08 to 0.93] vs 0.07 [-0.17 to 0.38] mm3/mm/year; p < 0.001) and ΔPI (2.0% [0.31% to 3.9%] vs 0.33% [-1.2% to 2.0%]; p < 0.001). Elevated UA levels were associated with a significantly increased risk of developing significant CAV progression (ΔPV >0.50 mm3/mm) (hazard ratio 2.2, 95% confidence interval 1.1 to 4.6; p = 0.037). Sirolimus resulted in decreased UA levels (5.8 ± 1.4 vs 5.2 ± 1.5; p = 0.002) and patients converted to sirolimus and had low UA levels had the least CAV progression (p < 0.001). After adjustment for potential confounders, change in UA level was also an independent predictor of CAV progression. UA is an independent predictor of CAV after HT. Sirolimus is associated with decreased UA levels and may explain one of the mechanisms by which sirolimus attenuates CAV progression.

A double blind placebo controlled randomized trial of the effect of acute uric acid changes on inflammatory markers in humans: A pilot study.

Uric acid has been linked with increased risk of chronic disease such as cardiovascular disease and this association has been attributed to a pro-inflammatory effect. Indeed, observational studies have shown that high uric acid is associated with high level of pro-inflammatory cytokines in the blood. However, whether high uric acid directly affects inflammation or rather represents a parallel defensive antioxidant mechanism in response to pathology that causes inflammation is unknown. To determine whether acute increase or decrease uric acid levels affects inflammation in healthy individuals, a randomized, placebo-controlled, double blind clinical study of uric acid or rasburicase with 20 healthy volunteers in each treatment-placebo group was conducted at the National Institute on Aging (NIA) Clinical Research Unit (CRU) at Harbor Hospital in Baltimore, MD. Change in inflammatory response was assessed by administering an oral lipid tolerance before and after the treatment of uric acid, rasburicase and placebo. Following uric acid administration, there was an accentuated increase in IL-6 during the oral lipid tolerance test (P<0.001). No significant differences were observed after lowering of uric acid with rasburicase. No side effects were reported throughout the trial. In health individuals, acute increase in uric acid results in an increased IL-6 response when challenged with lipid load. Such effect of amplification of inflammatory response may explain the higher risk of chronic diseases observed in subclinical hyperuricemia in observational studies.Trial Registration: ClinicalTrials.gov NCT01323335

Effects of chicory inulin on serum metabolites of uric acid, lipids, glucose, and abdominal fat deposition in quails induced by purine-rich diets.

Inulin, a group of dietary fibers, is reported to improve the metabolic disorders. In the present study, we investigated the effects of chicory inulin on serum metabolites of uric acid (UA), lipids, glucose, and abdominal fat deposition in quail model induced by a purine-rich diet. In this study, 60 male French quails were randomly allocated to five groups: CON (control group), MOD (model group), BEN (benzbromarone-treated group), CHI-H (high-dosage chicory inulin-treated group), and CHI-L (low-dosage chicory inulin-treated group). The serum UA level was significantly increased in the model group from days 7 to 28, as well as triglyceride (TG) and free fatty acid (FFA) increased later in the experimental period. The abdominal fat ratio was increased on day 28. Benzbromarone can decrease UA levels on days 14 and 28. The high and low dosage of chicory inulin also decreased serum UA levels on days 7, 14, and 28. The abdominal fat ratio, activity, and protein of acetyl-CoA carboxylase (ACC) were decreased in chicory inulin-treated groups. The activities of xanthine oxidase (XOD) and fatty acid synthase (FAS) were increased in the model group and decreased in the benzbromarone and chicory inulin groups. This study evaluated a quail model of induced hyperuricemia with other metabolic disorders caused by a high-purine diet. The results indicated that a purine-rich diet might contribute to the development of hyperuricemia, hypertriglyceridemia, and abdominal obesity. Chicory inulin decreased serum UA, TG, and abdominal fat deposition in a quail model of hyperuricemia by altering the ACC protein expression and FAS and XOD activities.

Homeostatic imbalance of purine catabolism in first-episode neuroleptic-naïve patients with schizophrenia.

BackgroundPurine catabolism may be an unappreciated, but important component of the homeostatic response of mitochondria to oxidant stress. Accumulating evidence suggests a pivotal role of oxidative stress in schizophrenia pathology.Methodology/Principal FindingsUsing high-pressure liquid chromatography coupled with a coulometric multi-electrode array system, we compared 6 purine metabolites simultaneously in plasma between first-episode neuroleptic-naïve patients with schizophrenia (FENNS, n = 25) and healthy controls (HC, n = 30), as well as between FENNS at baseline (BL) and 4 weeks (4w) after antipsychotic treatment. Significantly higher levels of xanthosine (Xant) and lower levels of guanine (G) were seen in both patient groups compared to HC subjects. Moreover, the ratios of G/guanosine (Gr), uric acid (UA)/Gr, and UA/Xant were significantly lower, whereas the ratio of Xant/G was significantly higher in FENNS-BL than in HC. Such changes remained in FENNS-4w with exception that the ratio of UA/Gr was normalized. All 3 groups had significant correlations between G and UA, and Xan and hypoxanthine (Hx). By contrast, correlations of UA with each of Xan and Hx, and the correlation of Xan with Gr were all quite significant for the HC but not for the FENNS. Finally, correlations of Gr with each of UA and G were significant for both HC and FENNS-BL but not for the FENNS-4w.Conclusions/SignificanceDuring purine catabolism, both conversions of Gr to G and of Xant to Xan are reversible. Decreased ratios of product to precursor suggested a shift favorable to Xant production from Xan, resulting in decreased UA levels in the FENNS. Specifically, the reduced UA/Gr ratio was nearly normalized after 4 weeks of antipsychotic treatment. In addition, there are tightly correlated precursor and product relationships within purine pathways; although some of these correlations persist across disease or medication status, others appear to be lost among FENNS. Taken together, these results suggest that the potential for steady formation of antioxidant UA from purine catabolism is altered early in the course of illness.

Updates in the Management of Gout

The majority of patients with gout are cared for by primary care physicians. Although both the physician and patient may easily recognize the acute arthritis of gout, errors in selecting the most appropriate medication and proper dose are common. The clinical stages of gout include asymptomatic hyperuricemia, intermittent gouty arthritis, and chronic tophaceous gout. Treatment of gout is usually considered after the first attack of arthritis, typically podagra. The aims of treatment are to alleviate the pain and inflammation associated with acute attacks, prevent future attacks, and decrease uric acid levels. Confusion frequently arises because certain medications such as colchicine may have dual purposes: to treat an acute attack and to suppress future attacks. The purpose of this management update is to provide practical advice about prescribing the proper medication considering both treatment goals and patient comorbidities.

Ethanol Fraction of Corn Silk (Zea mays L.) to Decrease Uric Acid Levels in Male White Mice

Corn silk (Zea mayz L.) were empirically used by the community in some regions as traditional remedies for hypertension,kidney stones,diabetes mellitus, urinary tractinfections and gout. This study aimed to determine the effect of corn silk ethanol fraction on decrease uric acid levels in male white mice.corn silk were extracted by macerate used 70% ethanol for 4 days.Urin acid test was performed on male mice induced by beef liver for 7 days.25 mice were grouped into 5 groups, groups dose I, II and III weregiven a fraction at a dose of 27.5 mg / bwBB, 55 mg / bwBB and 110 mg / bwBB, control given Na.CMC 0.5% and as positive controls were given allopurinol dose of 13 mg / bwBB. The five groups were treated orally 1 time a day for 7 days. Decreased uric acid levels were measured and observed on days 7 using an acid (easy touch). The results of ANOVA statistical analysis showed that negative controls gave a significant difference with positive controls, dose I, II and III because the sig value was