Reduction In Uric Acid Levels Research Articles

Continuous Positive Airway Pressure Treatment Does not Reduce Uric Acid Levels in OSA Women

ObjectivesAlthough an association between uric acid (UA) levels and obstructive sleep apnea (OSA) has been reported, the effect of continuous positive airway pressure (CPAP) on this measure is yet unclear. We aimed to investigate the effect of CPAP therapy on serum UA levels in patients with OSA. MethodsWe conducted a multicenter, open-label, randomized controlled trial in 307 women diagnosed with moderate-to-severe OSA (apnea-hypopnea index [AHI]≥15) in 19 Spanish Sleep Units. Women were randomized to CPAP (n=151) or conservative treatment (n=156) for 12 weeks. Changes in serum UA measures were assessed on an intention-to-treat basis. Additional analyses were conducted in the subgroup of women with CPAP adherence ≥4h/night and those with UA levels ≥6mg/dl. ResultsWomen had a mean (SD) age of 57.1 (10.1) years, median (first–third quartile) body mass index of 33.7 (29.0–38.5) mg/kg2 and AHI of 32.0 (22.6–48.5). The average serum UA measure was 5.11 (1.26) mg/dl, and 80 (26.1%) participants had UA≥6mg/dl. Compared with the control group, the CPAP group did not achieve any reduction in UA levels (non-adjusted intergroup difference −0.03mg/dl, 95%CI −0.20 to 0.13; p=0.702) after 12 weeks of follow-up. These results did not change when the analysis was restricted to women with CPAP adherence ≥4h/night, or the subgroup of women with hyperuricemia. ConclusionsTwelve weeks of CPAP therapy does not reduce UA levels compared to conservative treatment in women with moderate-to-severe OSA.

The Anti-hyperuricemic Effect of Torbangun (Coleus amboinicus Lour) Aqueous Extract

The study aimed to analyze the effect of Torbangun to reduction uric acid in woman with hypercholesterolemia. Design experiment used in this study was pre and post test controlled group design. The first step of this study was analyzed bioactive compound of torbangun aqueous extract. The next step was administired orally of Torbangun extract to control and woman with hypercholesterolemia for 30 days, with 30 subjects placed in two groups, viz, experimental (CC group) and placebo (PC group). The first group received one capsules of CC (each capsule contains 500 mg extract) while the second group received one capsules of PC (comprised of 500 mg fillers) one times daily for both groups. Uric acid (UA) and total cholesterol (TC) were measured in the first and the end of intervention. Oral administired of Torbangun extract exhibited reduce of hyper uric acid and hyper total cholesterol in woman with hypercholesterolemia. Data were analyzed with paired sample t test with 95% significance level. The results show that there was significant decrease in UA and TC on day 30, compared to control (PC group). In CC group, the capsules significant reduction in UA levels (p=0.001) and TC levels (p=0.000). Studies clearly demonstrated that Torbangun (Coleus amboinicus Lour) aqueous extract possesses antihyperuricemic activity in woman with hypercholesterolemia. Index Terms- uric acid, antihyperuricemic, torbangun extract

PENGARUH KONSELING DIET RENDAH PURIN DAN TINGGI OMEGA-3 TERHADAP KADAR ASAM URAT PASIEN GOUT RAWAT JALAN DI RUMAH SAKIT dr. A.K. GANI PALEMBANG TAHUN 2015

Industri menjadi salah satu sektor yang berperan penting dalam pengembangan wilayah, peningkatan ekonomi dan kesejahteraan penduduk. Hiperurisemia merupakan peningkatan konsentrasi asam urat darah. Konsumsi makanan seimbang, membatasi purin serta memilih makanan sumber omega-3 membantu mengurangi nyeri. Guna mempercepat proses penyembuhan, mengubah perilaku penderita agar mampu mengatasi penyakit asam urat dapat dilakukan dengan konseling gizi menggunakan leaflet. Tujuan penelitian adalah mengetahui pengaruh konseling diet rendah purin dan tinggi omega-3 terhadap kadar asam urat pasien gout. Jenis penelitian adalah penelitian kuasi eksperimen. Populasi dalam penelitian seluruh penderita gout yang berobat di RS dr. AK Gani Palembang. Sampel berjumlah 40 orang terbagi menjadi dua kelompok yaitu perlakuan dan pembanding diambil secara purposive sampling. Hasil analisis univariat menunjukkan 76% responden berjenis kelamin perempuan sebagian besar berumur 46-55 tahun (35%). Hasil analisisasupan zat gizi makro dan mikro memperlihatkan pada kelompok pembanding hanya asupan energi sebagian besar tergolong baik (55%). Kelompok perlakuan energi (60%), lemak (65%), omega-3 (55%), purin (80%) tergolong baik.Hasil analisis bivariat menunjukkan rata-rata penurunan kadar asam urat sebelum dan sesudah diberikan konseling diet rendah purin yaitu sebesar 2,01 mg/dL.Dapat disimpulkan ada pengaruh konseling diet rendah purin dan tinggi omega-3 terhadap penurunan kadar asam urat nilai p = 0,004

Changes in the Serum Urate Level Can Predict the Development of Parkinsonism in the 6-Hydroxydopamine Animal Model.

Epidemiological studies indicate that a higher plasma level of uric acid (UA) associates with the reduced risk of Parkinson's disease (PD). To confirm the role of UA as a biomarker for PD, we evaluated changes in the serum UA level in the 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonism in rat. For this purpose, 6-OHDA was administered in the medial forebrain bundle by stereotaxic surgery. According to the apomorphine-induced rotational test, the increased intensity of behavioral symptoms as a function of time was associated with the further reduction of UA level. On the other hand, the level of UA increased in the midbrain of the injured hemisphere. The level of reduction in the serum UA level of rats with severe and moderate symptoms was significantly higher than that of rats with mild symptoms. The immunohistofluorescence and biochemical analyses showed that the serum UA level was also correlated with the death of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra pars compacta (SNc), reduced level of striatal dopamine, and severity of oxidative stress in the midbrain. The rats with mild symptoms also showed a significant decrease in TH-positive neurons and striatal dopamine level. These findings suggest a positive correlation between the level of reduction in the serum urate level and severity of 6-OHDA-induced Parkinsonism. In addition, our findings indicated that UA had no marked neuroprotective effects, at least at concentrations obtained in this study. On the other hand, UA was introduced as a biomarker for PD, as a significant decline was observed in the serum UA level of rats with mild behavioral symptoms but with significant dopaminergic cell death in the SNc.

Effects of adjunctive N-acetylcysteine on depressive symptoms: Modulation by baseline high-sensitivity C-reactive protein

Outcomes in a RCTs of 12 weeks of theclinical efficacy of N-acetylcysteine (NAC) as an adjunctive treatment on depression and anxiety symptoms and its effects on high-sensitivity C-reactive protein (hs-CRP) levels. A wide array of measures were made. The 17-item version of the Hamilton Depression Rating Scale (HDRS17); the Hamilton Anxiety Rating Scale (HAM-A); Sheehan Disability Scale; Quality of Life; Clinical Global Impression (CGI); anthropometrics measures; and vital signs and biochemical laboratory. There were no significant differences among the groups regarding demographic, clinical features, use of medication, metabolic syndrome and comorbidities. From baseline to week 12, individuals receiving NAC, versus placebo, had a statistically significant reduction in depressive symptoms on HDRS17 (p < 0.01) and anxiety symptoms on HAM-A (p = 0.04), but only for individuals with levels of hs-CRP > 3 mg/L at baseline. Individuals receiving NAC with baseline levels of hs-CRP > 3 mg/L, had more significant reduction in uric acid levels compared to individuals with baseline levels of hs-CRP ≤ 3 mg/L on week 12. Participants receiving placebogained significantly more weight during the 12 weeks for baseline levels of hs-CRP ≤ 3 mg/L and hs-CRP > 3 mg/L, and individuals receiving NAC in both groups did not have significant weight change during the 12 weeks. No individuals were withdrawn from the study because of adverse event. NAC group exhibited significantly greater reduction on hs-CRP levels than placebo group from baseline to week 12. Trial registration: clinicaltrials.gov Identifier; NCT02252341

Maternal Selenium Supplementation Enhanced Skeletal Muscle Development Through Increasing Protein Synthesis and SelW mRNA Levels of their Offspring.

The present study aimed to investigate the influence of maternal selenium supplementation on the skeletal muscle development of the offspring. A total of 720 Ross 308 broiler breeders at 24-week-old were allocated into 3 treatments with 6 replicates of 40 hens each and fed with 0mg/kg-(group Se/C), 0.5mg/kg organic-(group Se/O), and 0.5mg/kg inorganic-(group Se/I) selenium, respectively for 8weeks. The male offspring from each nutritional treatment were divided and housed into 8 cages of 12 birds each and fed with a commercial diet supplemented with selenium from Na2SeO3 at 0.15mg/kg. Results showed that Se/O group had the highest selenium deposition (P < 0.05) in the egg yolk and albumen. Furthermore, maternal selenium supplementation promoted breast muscle yield; increased serum insulin and IGF-I concentration; upregulated AKT, mammalian target of rapamycin (mTOR), P70S6K, Myf5, MyoD, MyoG, and SelW mRNA levels; and improved the phosphorylation of AKT at Serine 473 residue, mTOR at Serine 2448 residue, and FOXO at Serine 256 residue in skeletal muscles of the offspring. In contrast, the hens' diet supplemented with selenium could result in reduction of uric acid level in serum and downregulation of Atrogin-1 and MuRF1 mRNA levels in the skeletal muscle of the offspring. Additionally, no significant effect on the skeletal muscle development post-hatch was observed between organic and inorganic selenium supplementation. In conclusion, maternal organic selenium supplementation improved selenium deposition in egg; however, no significant effect has been detected on the breast muscle development of the offspring of broiler breeder compared with inorganic selenium supplementation.

Nutrition Counseling among Patients with Gout

Hyperuricemia (high levels of uric acid in the blood) can cause a buildup of monosodium urate crystals. Sudden increase may lead to gout attacks. Consumption of an unbalanced diet, intake of proteins containing high purine is one of the factors that affect gout arthritis. Based on data from medical records at the hospital Mohamad Palembang Hoesin and increase in the number of visits patients with gout, the cumulative incidence of gout reached 22 % after 5 years, the uric acid levels &amp;gt; 9 mg / dL. One of the efforts to help clients change behavior and accelerate the healing process that nutritional counseling is conducted face to face using leaflets media. The purpose of this study was to determine the effectiveness of low-purine diet counseling against uric acid levels in gout patients who were treated at the Hospital dr. AK Gani Palembang. Is a quasi-experimental study design, this study indicated that nutrition counseling with low-purine diet will help to change the behavior of people with gout in the diet to accelerate the reduction in uric acid levels. The average reduction in uric acid levels after being given a lowpurine diet counseling that is equal to 1.6 mg/dL and concluded that giving low-purine diet counseling are effective in lowering uric acid levels in patients with gout. Based on these results, low-purine diet counseling should be offered to patients with gout in an effort to motivate behavior change and reduction in uric acid levels. Nutrition counseling with Low-purine diet in patients with gout can change the eating habits of patients who eventually decreased the levels of uric acid.

Effects of Sodium Glucose Cotransporter-2 Inhibitors on Serum Uric Acid in Type 2 Diabetes Mellitus.

Hyperuricemia has been linked to metabolic syndrome, cardiovascular disease, and chronic kidney disease. Hyperuricemia and type 2 diabetes mellitus were inter-related, type 2 diabetes mellitus was more at risk of having a higher serum uric acid level, and also individuals with higher serum uric acid had higher risk of developing type 2 diabetes in the future. Insulin resistance seems to play an important role in the causal relationship between metabolic syndrome, type 2 diabetes, and hyperuricemia. Oral diabetic drugs that would have additional beneficial effects on reducing serum uric acid levels are of importance. Selective SGLT2 inhibitors were extensively studied in type 2 diabetes mellitus and were found to have improvement of glycemic control, in addition to their proven metabolic effects on weight and blood pressure. Additional beneficial effect of SGLT2 inhibitors on serum uric acid level reduction is investigated. Recently, data have been accumulating showing that they have additional beneficial effects on serum uric acid reduction. As for the postulated mechanism, serum uric acid decreased in SGLT2 inhibitor users as a result of the increase in the urinary excretion rate of uric acid, due to the inhibition of uric acid reabsorption mediated by the effect of the drug on the GLUT9 isoform 2, located at the collecting duct of the renal tubule.

Influence of the Herbicide Facet® on Corticosterone Levels, Plasma Metabolites, and Antioxidant System in the Liver and Muscle of American Bullfrog Tadpoles

This study sought to analyze the effects of the herbicide quinclorac on body condition indices; plasma levels of corticosterone, glucose, and uric acid; activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST); and levels of lipid peroxidation (LPO) in the liver and caudal muscle of American bullfrog (Rana catesbeiana) tadpoles. After a 7-day acclimation period, animals were exposed to four concentrations (0.05, 0.1, 0.2, and 0.4 μg/L) of herbicide for a further 7 days. Then, blood samples were obtained, animals were euthanized, and the liver and caudal muscle resected. Levels of corticosterone and uric acid were reduced in tadpoles exposed to the highest concentration of herbicide, and this reduction was preceded by an increase in glucose levels. In the liver tissue, LPO was increased after exposure to 0.1 μg/L quinclorac, followed by a return to baseline values in the remaining concentrations; this response was accompanied by an increase in SOD and GST and reduction of tissue protein levels. At the highest concentration, a reduction in activity of all enzymes was observed, with protein returning to control-like levels. In muscle, SOD and GST levels declined with exposures up to 0.1 g/L and 0.4 μg/L, respectively, whereas LPO decreased in animals exposed to 0.1 μg/L. These results suggest participation of nonenzymatic antioxidant defenses, as demonstrated by the reduction in uric acid levels. Exposure to the range of quinclorac concentrations used in this study slowed body mass and length gain, reduced corticosterone levels, and modulated antioxidant defenses.

Effects of canagliflozin on cardiovascular risk factors in patients with type 2 diabetes mellitus.

SummaryBackground and aimsCardiovascular disease is the most common cause of morbidity and mortality among people with type 2 diabetes mellitus (T2DM). The main contributors to cardiovascular risk in T2DM are chronic hyperglycaemia, reduced insulin sensitivity, hypertension and dyslipidaemia. Other cardiovascular risk factors include obesity and visceral adiposity, increased arterial stiffness and renal dysfunction. Results from clinical trials, including a long‐term cardiovascular outcome study, have shown that sodium glucose co‐transporter 2 (SGLT2) inhibitors can provide multiple cardiometabolic benefits beyond glycaemic control including inducing mild osmotic diuresis, natriuresis and weight loss. This review article describes the effects of canagliflozin on cardiovascular risk factors based on results from its clinical development programme.MethodsThis review is based on structured searches to identify literature related to the effects of canagliflozin on cardiovascular risk factors in patients with T2DM.Discussion and conclusionsCanagliflozin treatment has been shown to provide glycaemic improvements as well as reductions in blood pressure and body weight across a broad range of patients with T2DM, including those with elevated cardiovascular risk. Other observed effects of canagliflozin that may contribute to improved cardiometabolic outcomes include reduction in uric acid levels, decreased albuminuria and increases in serum magnesium. Results of ongoing long‐term cardiovascular outcomes studies of canagliflozin are expected to provide additional evidence on the cardiometabolic effects of canagliflozin treatment.

Gout in primary care: Can we improve patient outcomes?

In the United Kingdom, gout represents one of the most common inflammatory arthropathies predominantly managed in the primary care setting. Gout is a red flag indicator for cardiovascular disease and...

Oral delivery of allopurinol niosomes in treatment of gout in animal model

Context: Gout is a painful disorder which does not have an efficient delivery system for its treatment.Objective: Development and in vitro, in vivo evaluation of allopurinol-loaded nonionic surfactant-based niosomes was envisaged.Materials and methods: Niosomes were prepared with Span 20 and Tween 20 (1:1 molar ratio) using ether injection method. The formulations were screened for entrapment efficiency, particle size analysis, zeta potential, release kinetics, in vivo activity, and stability studies.Result: Stable, spherical vesicles of average particle size 304 nm with zeta-potential and entrapment efficiency of 22.2 mV and 79.44 ± 0.02%, respectively, were produced. In vitro release study revealed 82.16 ± 0.04% release of allopurinol within 24 h. The niosomal formulation was further evaluated for its antigout potential in monosodium urate (MSU) crystal induced gout animal model. The formulation demonstrated significant uric acid level reduction and enhanced antigout activity when compared with the pure allopurinol.Discussion: The better antigout activity displayed by niosomal formulation could be attributed to sustained release of drug, higher drug solubility within biological fluids, better membrane interaction, smaller size, and presence of cholesterol and surfactant.Conclusions: This study reveals that niosomes can be an efficient delivery system for the treatment of gout.

Empagliflozin. Results of the EMPA-REG OUTCOME trial. A breakthrough in treatment of type 2 diabetes?

Cardiovascular (CV) complications are the main health challenge among type 2 diabetic patients. They may cause premature death, disability and reduce the quality of life. Administering a multifactorial intervention aimed at controlling glycaemia, lipaemia and arterial blood pressure allows to reduce the risk of their occurrence. FDA ruled that all newly introduced hypoglycaemic agents must undergo tests for CV safety. The EMPAREG OUTCOME trial was conducted on a group of type 2 diabetic patients at high CV risk. It showed that including empagliflozin in the standard therapy reduces the risk of primary outcome (death from CV causes, non-fatal myocardial infarction or non-fatal stroke) by 14% and all-cause mortality by 32%. The causes of this effect of empagliflozin — an inhibitor of SGLT2, which is an enzyme present only in renal proximal tubules — are unclear. Reduction in insulin resistance and in oxidative stress, changes in lipid levels, reduction in uric acid levels, in albuminuria, in blood pressure and reduction in sympathetic activity are all named as potential mechanisms underlying the rotective effect of empagliflozin. Results of the EMPA-REG OUTCOME trial are a breakthrough in the treatment of diabetes, and if other SGLT2 inhibitors are found to have similar effects, a fundamental change in therapy recommendations for this patient population may be made.

Tuna extract reduces serum uric acid in gout-free subjects with insignificantly high serum uric acid: A randomized controlled trial.

Long-term reduction of serum urate levels is vital in the treatment of gout. However, it is difficult to convince gout-free individuals of the necessity of treatment as few appropriate over-the-counter remedies and dietary supplements are available. Therefore, the present study aimed to investigate the antihyperuricemic efficacy and safety of a tuna extract containing the imidazole compounds to evaluate its potential as a functional food ingredient. A randomized, 4-week, double-blind, placebo-controlled study was conducted. A total of 48 male gout-free subjects with insignificantly high serum uric acid were randomly assigned to low- and high-dose tuna extract groups or a placebo group. The efficacy of the extract was assessed by measuring serum uric acid levels. Furthermore, a safety assessment was performed by physical parameters, hematology, blood biochemistry and urinalysis. The results indicated that the uric acid level was decreased at week 4 during the intervention in the tuna extract groups (low and high dose, -0.23 and -0.34 mg/dl, respectively) compared to the placebo group (-0.07 mg/dl). At week 4 after the intervention, a significant reduction in uric acid levels (-0.41 mg/dl; P<0.05) was observed in the high-dose tuna extract group compared with the placebo group (+0.11 mg/dl). No dose-related adverse events were observed during and following the intervention. Therefore, the present results suggest that oral administration of tuna extract containing the imidazole compounds has hypouricemic activity with no undesirable side effects.

Spinal gout: A review with case illustration.

AIMTo summarize clinical presentations and treatment options of spinal gout in the literature from 2000 to 2014, and present theories for possible mechanism of spinal gout formation.METHODSThe authors reviewed 68 published cases of spinal gout, which were collected by searching “spinal gout” on PubMed from 2000 to 2014. The data were analyzed for clinical features, anatomical location of spinal gout, laboratory studies, imaging studies, and treatment choices.RESULTSOf the 68 patients reviewed, the most common clinical presentation was back or neck pain in 69.1% of patients. The most common laboratory study was elevated uric acid levels in 66.2% of patients. The most common diagnostic image finding was hypointense lesion of the gout tophi on the T1-weighted magnetic resonance imaging scan. The most common surgical treatment performed was a laminectomy in 51.5% and non-surgical treatment was performed in 29.4% of patients.CONCLUSIONSpinal gout most commonly present as back or neck pain with majority of reported patients with elevated uric acid. The diagnosis of spinal gout is confirmed with the presence of negatively birefringent monosodium urate crystals in tissue. Treatment for spinal gout involves medication for the reduction of uric acid level and surgery if patient symptoms failed to respond to medical treatment.

A Randomized Controlled Trial of Allopurinol in Patients With Peripheral Arterial Disease

BackgroundPatients with peripheral arterial disease (PAD) are limited by intermittent claudication in the distance they can walk. Allopurinol has been shown in coronary arterial disease to prolong exercise before angina occurs, likely by prevention of oxygen wastage in tissues and reduction of harmful oxidative stress. MethodsIn this study we evaluated whether allopurinol could prolong the time to development of leg pain in participants with PAD. In a double-blind, randomized controlled clinical trial participants were randomized to receive either allopurinol 300 mg twice daily or placebo for 6 months. The primary outcome was change in exercise capacity on treadmill testing at 6 months. Secondary outcomes were 6-minute walking distance, Walking Impairment Questionnaire, SF-36 questionnaire, flow-mediated dilatation, and oxidized low-density lipoprotein. Outcome measures were repeated midstudy and at the end of study. The mean age of the 50 participants was 68.4 ± 1.2 years with 39 of 50 (78%) male. ResultsFive participants withdrew during the study (2 active, 3 placebo). There was a significant reduction in uric acid levels in those who received active treatment of 52.1% (P < 0.001), but no significant change in either the pain-free or the maximum walking distance. Other measures of exercise capacity, blood vessel function, and the participants' own assessment of their health and walking ability also did not change during the course of the study. ConclusionsAlthough allopurinol has been shown to be of benefit in a number of other diseases, in this study there was no evidence of any improvement after treatment in patients with PAD.

Fixed, low-dose rasburicase for the treatment or prevention of hyperuricemia in adult oncology patients

Rasburicase is a recombinant urate oxidase enzyme administered to high risk patients or to those with preexisting hyperuricemia from tumor lysis syndrome (TLS). The objective of this retrospective review is to evaluate and characterize the use of fixed, low-dose rasburicase for the treatment of hyperuricemia in adult patients. A retrospective chart review from 1 October 2005 to 31 December 2011 was conducted in adult oncology patients who received fixed, low-dose rasburicase. Patients who met the inclusion criteria were evaluated for the uric acid level change from baseline and the achievement of uric acid level less than 8 mg/dL. Forty-five patients were included in the analysis in which 26 (58%) patients received 3 mg rasburicase. For the 39 patients with baseline uric acid levels 8 mg/dL or higher, 80% achieved a uric acid level lower than 8 mg/dL with a single rasburicase dose. Six patients (13%) required renal replacement therapy despite rasburicase. The median uric acid level reduction 24 h post rasburicase dose 1.5 mg, 3 mg, 4.5 mg, and 6 mg were 5.5, 5.8, 3.8, and 10.05 mg/dL, respectively. There was no clinical difference between obese and non-obese patients in terms of their median uric acid reduction, 5.5 vs. 7 mg/dL, respectively. Fixed, low dose rasburicase produced a consistent lowering of uric acid levels and may be utilized in the management of hyperuricemia in TLS. Further study is necessary to determine if a larger fixed dose would be required in those patients with a higher baseline uric acid level.

Phase I Study of Urate Oxidase in the Reduction of Acute Graft-Versus-Host Disease after Myeloablative Allogeneic Stem Cell Transplantation

Graft-versus-host disease (GVHD) is a donor T cell driven response against host tissue that can complicate allogeneic hematopoietic stem cell transplantation (HSCT). During acute GVHD, endogenous adjuvants such as uric acid are released by damaged host tissue, activating alloreactive donor T cells. A phase I study was conducted at the Massachusetts General Hospital between 2007 and 2010 to test the hypothesis that reduction of uric acid levels during allogeneic HSCT can modulate the development of acute GVHD. Twenty-one patients with hematologic malignancies in complete remission undergoing myeloablative peripheral blood HSCT received recombinant urate oxidase at .20 mg/kg for 5 consecutive days during conditioning. Results were compared with all patients who underwent allogeneic HSCT at our institution during the same time period who met the same inclusion and exclusion criteria but were not enrolled in the study. The only major adverse event was a case of hemolytic anemia in a patient who had glucose-6-phosphate dehydrogenase deficiency. Primary outcome was the cumulative incidence of grades II to IV acute GVHD, which was significantly decreased in the treatment group in the intention-to-treat analysis (57% [12/21] versus 24% [5/21], P = .036) and in the per-protocol analysis (P = .017). Patients who developed acute GVHD had a higher level of serum uric acid during the pretransplantation period compared with those who did not (P < .001). There was no difference in disease-free or overall survival. Our study suggests that urate oxidase can be safely administered during myeloablative conditioning and may reduce the incidence of acute GVHD.

Study on the correlation between constituents detected in serum from Rhizoma Smilacis Glabrae and the reduction of uric acid levels in hyperuricemia

Ethnopharmacological relevanceRhizoma Smilacis Glabrae (RSG) has been used in the clinical treatment of gout and hyperuricemia in China for thousands of years. Modern pharmacological studies have shown that RSG exhibits hypouricemic effects because of its significant inhibitory effect on the activity of xanthine oxidase. Materials and methodsThe Rhizoma Smilacis Glabrae extract (RSGE) at 1mL/100g oral administration was demonstrated to possess in vivo potent hypouricemic effects in hyperuricemic rats pretreated with oxonic acid potassium salt (200mg/kg, 2mL/kg). UPLC–MS was used to identify the constituents absorbed in the serum. In addition, a bivariate correlation analysis between the changes in the relative contents of the constituents from RSGE detected by HPLC and the serum uric acid levels in hyperuricemic rats at different points in time was used to calculate their correlation coefficients. ResultsA total of 14 constituents were observed in the RSGE-treated rat serum, and 11 of these were inferred. An RSGE constituent was considered correlated with the hypouricemic effects if its correlation coefficient was above 0.5. The results suggested that only seven of the constituents absorbed in the serum of the hyperuricemic rats were correlated with hypouricemic effects, namely, palmitic acid, 3′-O-methyltaxifolin glucuronide, 3′-O-methyiastilbin glucuronide, astilbin glucuronide, 5-O-caffeoylshikimic acid glucuronide, resveratrol glucuronide, and dihydrokaempferol. ConclusionThese findings provide potent evidence for the study on RSG as a pharmacodynamic material basis and for developing RSG as a safe and promising natural drug to prevent hyperuricemia and gout instead of allopurinol.

Costs and Outcomes Associated with Rasburicase Versus Allopurinol in Patients with Tumor Lysis Syndrome.

AbstractAbstract 3175 Background:Tumor lysis syndrome (TLS) is an oncologic emergency resulting in several metabolic abnormalities (Cairo et al, BJH, 2004). Hyperuricemia and its associated complications are the most frequent manifestations of TLS. For decades, treatment has consisted of hydration, urine alkalinization, and administration of allopurinol (Cairo et al BJH, 2011). However, recent clinical trials have shown that initiation of rasburicase, a hypouricemic agent, within four hours significantly reduces high uric acid (UA) levels in patients experiencing TLS (Goldman et al Blood, 2001). Studies demonstrate that rasburicase is safe and effective, has excellent tolerability, and is potentially cost-effective in patients at high risk for TLS. Objective:The objective of this retrospective analysis was to evaluate real-world differences in UA levels, length of stay and costs for patients initiating treatment with rasburicase compared to patients receiving allopurinol. Methods:A retrospective study, spanning January 1, 2005 to March 31, 2009, was conducted utilizing administrative data from more than 400 U.S. hospitals. Hospitalized patients with clinically confirmed TLS, who received rasburicase or allopurinol during the study period were eligible for inclusion. Patients with a diagnosis of gout, as determined by the presence of an ICD-9 diagnosis code 274.x, were excluded from the study. Patients receiving rasburicase were propensity score matched to allopurinol-treated patients in a 1:4 ratio based on time between hospital admission and treatment initiation, baseline UA level, cancer type, age, gender, race, hospital characteristics, payer type, and prior intensive-care unit (ICU) admission. Differences in length of stay (LOS), changes in UA levels and serum creatinine, days in the ICU, and costs per percent of UA reduction were assessed through various statistical models. Due to a high level of missing cancer diagnosis, comparative results of rasburicase and allopurinol were also evaluated through sensitivity analysis to test the robustness of the results. Results:A total of 130 patients were identified, matched and included in this study; 26 initiated treatment with rasburicase and 104 were treated with allopurinol. Patients were predominately male (∼61%) Caucasian (∼76%) with an average age of 55 years. There were no statistically significant differences among baseline variables between the two cohorts. Prior to initiating treatment, mean UA levels were 11.4 mg/dL for the rasburicase cohort and 11.2 mg/dL for allopurinol cohort. By the second day of treatment mean UA levels were 5.3 mg/dL (p<0.0001) lower for rasburicase (2.7mg/dL) compared to allopurinol (8.0 mg/dL). Changes in potassium, phosphorus and creatinine levels were not statistically different across the two cohorts. The LOS for patients in the rasburicase cohort averaged 11.5 days compared to 16.5 days for allopurinol patients (p=0.0212); rasburicase patients also had a lower ICU LOS, 1.4 and 3.9 days, respectively (p<0.0001). The reduction in LOS correlated with a reduction in costs, which averaged $34,065 per rasburicase patient compared to $54,103 per allopurinol patient (p=0.0205). Results of the sensitivity analyses did not change the overall findings. [Display omitted] [Display omitted] [Display omitted] Conclusions:This retrospective study, using hospital administrative data, revealed that treatment with rasburicase, compared with allopurinol, was associated with a significant reduction in UA levels, ICU LOS, overall LOS and overall costs per patient. Despite the increase pharmaceutical costs of rasburicase versus allopurinol, the use of rasburicase in patients with TLS is cost effective and reduces LOS. Disclosures:Cairo:sanofi aventis: Consultancy. Thompson:sanofi aventis: Employment. Tangirala:sanofi aventis: Employment. Eaddy:Xcenda: Employment.