allopurinol and Hyperlipidemias

Topics: Acidosis; Acute Kidney Injury; Allopurinol; Aluminum Hydroxide; Burkitt Lymphoma; Child; Humans; Hypercalcemia; Hyperlipidemias; Hypertension, Renal; Hypoglycemia; Lymphoma; Male; Mannitol; Metabolic Diseases; Phosphorus Metabolism Disorders; Uric Acid; Xanthines

Topics: Adult; Alcoholism; Cholesterol, Dietary; Chylomicrons; Diet, Reducing; Dietary Fats; Female; Gout; Humans; Hyperlipidemias; Purine-Pyrimidine Metabolism, Inborn Errors; Triglycerides; Uricosuric Agents; Xanthine Oxidase

The purpose of this study was to compare urate-lowering (UL) efficacy and safety of daily febuxostat and allopurinol in subjects with gout and serum urate (sUA) > or = 8.0 mg/dL in a six-month trial.. Subjects (n = 2,269) were randomized to febuxostat 40 mg or 80 mg, or allopurinol 300 mg (200 mg in moderate renal impairment). Endpoints included the proportion of all subjects with sUA <6.0 mg/dL and the proportion of subjects with mild/moderate renal impairment and sUA <6.0 mg/dL. Safety assessments included blinded adjudication of each cardiovascular (CV) adverse event (AE) and death.. Comorbidities included: renal impairment (65%); obesity (64%); hyperlipidemia (42%); and hypertension (53%). In febuxostat 40 mg, febuxostat 80 mg, and allopurinol groups, primary endpoint was achieved in 45%, 67%, and 42%, respectively. Febuxostat 40 mg UL was statistically non-inferior to allopurinol, but febuxostat 80 mg was superior to both (P < 0.001). Achievement of target sUA in subjects with renal impairment was also superior with febuxostat 80 mg (72%; P < 0.001) compared with febuxostat 40 mg (50%) or allopurinol (42%), but febuxostat 40 mg showed greater efficacy than allopurinol (P = 0.021). Rates of AEs did not differ across treatment groups. Adjudicated (APTC) CV event rates were 0.0% for febuxostat 40 mg and 0.4% for both febuxostat 80 mg and allopurinol. One death occurred in each febuxostat group and three in the allopurinol group.. Urate-lowering efficacy of febuxostat 80 mg exceeded that of febuxostat 40 mg and allopurinol (300/200 mg), which were comparable. In subjects with mild/moderate renal impairment, both febuxostat doses were more efficacious than allopurinol and equally safe. At the doses tested, safety of febuxostat and allopurinol was comparable.. NCT00430248.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Comorbidity; Dose-Response Relationship, Drug; Febuxostat; Female; Gout; Gout Suppressants; Humans; Hyperlipidemias; Hypertension; Hyperuricemia; Kidney Diseases; Male; Middle Aged; Obesity; Thiazoles; Treatment Outcome; United States; Uric Acid; Young Adult

The serum uric acid lowering effects of 100 mg Allopurinol (A), 20 mg Benzbromarone (B) and the combination of both were tested in a randomized block-trial in 12 male patients suffering from hyperuricemia and hyperlipoproteinemia type IIb/IV. Therapy periods lasted 4 weeks each. Allopurinol lowered the uric acid concentrations from 7,54 mg/100 ml to 5,95 mg/100 ml, Benzbromarone from 7,54 mg/100 ml to 6,11 mg/100 ml and the combination from 7,54 mg/100 ml to 4,90 mg/100 ml, all three significantly. The difference between the effect of the combination drug and Allopurinol and Benzbromarone respectively was also significant. An additive effect of both components is evident. Serum creatinin concentration remained constant. Uric acid and creatinin excretion could not be evaluated because of failure of patient compliance in the collecting of urine.

Topics: Adult; Allopurinol; Benzbromarone; Benzofurans; Drug Combinations; Humans; Hyperlipidemias; Male; Middle Aged; Triglycerides; Uric Acid

The aim of this project was to determine the effects of a package of care for gout in primary care.. An audit of gout management in a single rural medical practice was undertaken before (in 2012) and after (in 2015) the introduction of the package of care reflecting guidelines in gout management.. There was a statistically significant increase in the number of individuals commenced on allopurinol ≤100 mg/d and a decrease in the number commenced on allopurinol ≥200 mg/d (P <0.001). The number of times each patient had serum urate tested between 2012 and 2015 (median [range] 1 [0-3] versus 2 [0-10], respectively; P <0.001). Of those individuals who had at least one serum urate measurement, the number of individuals who were never at target urate was 43 out of 67 (64.2%) in 2012, compared with 52 out of 133 (39.1%) in 2015 (P = 0.001).. A package of care can improve adherence to gout management guidelines in primary care.

Topics: Aged; Allopurinol; Clinical Audit; Clinical Chemistry Tests; Clinical Protocols; Colchicine; Comorbidity; Diabetes Mellitus; Disease Management; Female; Gout; Gout Suppressants; Guideline Adherence; Humans; Hyperlipidemias; Hypertension; Hyperuricemia; Male; Mass Screening; Middle Aged; New Zealand; Obesity; Patient Education as Topic; Practice Guidelines as Topic; Primary Health Care; Referral and Consultation; Renal Insufficiency, Chronic; Rheumatology; Rural Population; Uric Acid

This study aimed to determine colorectal cancer (CRC) risks among patients with gout through a follow-up study on a nationwide population-based cohort that included patients with gout and the general population in Taiwan.. From the Taiwan National Health Insurance Research Database, we identified 28 061 patients who were newly diagnosed with gout between 2000 and 2010 as the study cohort. We randomly selected 84 248 subjects matching in gender, age and baseline year as comparison cohort. The cohorts were followed up until CRC occurrence, withdrawal from the system of National Health Insurance, or Dec. 31, 2013.. Cumulative incidences and incidence rate ratios (IRRs) of CRC between two cohorts were examined. The Cox proportional hazards model was used to evaluate risk factors associated with CRC development.. During the 13-year follow-up, the incidence rate of CRC development in the gout cohort reached 2.44 per 1000 person-years, which was higher than the 2.13 per 1000 person-years in the control cohort (IRR=1.15; 95% CI 1.04 to 1.26). After adjusting for age, gender, urbanisation status and comorbidities, including hypertension, diabetes and hyperlipidaemia, gout showed no significant association with increased risk of CRC occurrence (adjusted HR=1.03; 95% CI 0.93 to 1.14).. Similar risks of CRC incidence were observed in patients with and without gout in Taiwan. Allopurinol and colchicine are commonly used as urate-lowering drug and anti-inflammation medication in Taiwan and had been shown to reduce the risk of CRC incidence. Thus, further pharmaco-epidemiological studies should be carried out to specifically assess the role of allopurinol in the relationship between gout and CRC.

Topics: Adult; Aged; Allopurinol; Colchicine; Colorectal Neoplasms; Comorbidity; Databases, Factual; Diabetes Mellitus; Female; Follow-Up Studies; Gout; Humans; Hyperlipidemias; Hypertension; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Proportional Hazards Models; Retrospective Studies; Risk Factors; Taiwan

Gout is increasingly recognized as the most common form of inflammatory arthritis worldwide; however, no Canadian data on the disease burden of gout are available. We estimated the prevalence, incidence, prescription patterns, and comorbidity burden of gout in an entire Canadian province [British Columbia (BC)] over the last decade.. We utilized PopulationData BC, a province-wide database, to estimate temporal trends in the prevalence and incidence of gout from 2000 to 2012, as well as according to age category. Annual estimates were age-sex-standardized using 2012 as the reference. We also examined annual trends in prescription patterns of common gout medications and assessed the comorbidity burden among gout patients in 2012.. The 2012 prevalence of gout was 3.8% among the overall population, and the incidence rate was 2.9 per 1000 person-years. Both gout prevalence and incidence increased substantially over the study period. This burden additionally increased according to age category, affecting over 8% of those ages 60-69 years in 2012. Approximately 22% of gout patients received a prescription for urate-lowering therapy (ULT), which remained stable over the study period, while colchicine and oral glucocorticoid use both increased modestly. By 2012, 72%, 52%, and 18% of prevalent gout patients had been diagnosed with hypertension, hyperlipidemia, and diabetes, respectively.. The burden of gout in BC, Canada, is substantial, and both the prevalence and incidence have increased over the past decade, while prescription of ULT remains low. These data support the need to improve gout prevention and care.

Topics: Aged; Allopurinol; Anti-Inflammatory Agents, Non-Steroidal; British Columbia; Colchicine; Comorbidity; Diabetes Mellitus; Febuxostat; Female; Glucocorticoids; Gout; Gout Suppressants; Humans; Hyperlipidemias; Hypertension; Incidence; Male; Middle Aged; Population Growth; Prevalence; Probenecid; Sulfinpyrazone; Uricosuric Agents

The aim of this study was to investigate possible effects of high cholesterol diet on oxidant/antioxidant status in rabbit kidney tissues.. Although a number of experimental animal models have suggested that hyperlipidemia is associated with progressive kidney failure data remain sparse on the role of dietary cholesterol intake on kidney disease.. Twelve male New Zealand albino rabbits were randomly divided into two groups (control and cholesterol). Both groups were fed on a standard laboratory diet. Animals in the cholesterol group additionally received cholesterol (1 g/kg/day), orally. The study period was 12 weeks. Activities of catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), nitric oxide synthase (NOS), xanthine oxidase (XO), paraoxonase (PON), adenosine deaminase (ADA) enzymes and levels of malondialdehyde (MDA) and nitric oxide (NO) were measured in kidney tissue samples. Histological examination of the kidney tissue samples was also done.. SOD, GSH-Px and XO enzyme activities were found to be decreased and NOS and PON activities increased significantly in cholesterol group compared to controls. As an indication of oxidation, MDA levels were found to be increased in cholesterol group. Histological examination revealed some derangements in the kidney tissue.. High cholesterol diet creates oxidant load and causes peroxidation, which in turn, leads derangements in the rabbit kidney tissue (Tab. 2, Fig. 2, Ref. 69).

Topics: Animals; Antioxidants; Catalase; Cholesterol, Dietary; Diet, High-Fat; Disease Models, Animal; Glutathione Peroxidase; Hyperlipidemias; Kidney; Male; Malondialdehyde; Nitric Oxide; Nitric Oxide Synthase; Oxidants; Rabbits; Superoxide Dismutase; Xanthine Oxidase

A series of novel indole-chalcone fibrates were synthesized and their hypolipidemic activity was evaluated in triton WR-1339 induced hyperlipidemic rat model. Preliminary studies indicated that the hybrids 19, 24 and 29 exhibited potent in vitro antioxidant and significant in vivo antidyslipidemic effects. Our results suggest that these new hybrid architectures may serve as promising leads for the development of next generation lipid lowering agents.

Topics: Animals; Antioxidants; Chalcone; Disease Models, Animal; Drug Design; Hyperlipidemias; Hypolipidemic Agents; Indoles; Lipoproteins; Lipoproteins, HDL; Lipoproteins, LDL; Male; Molecular Structure; Polyethylene Glycols; Rats

Andrographis paniculata, native to Taiwan, Mainland China and India, is a medicinal herb, which possesses various biological activities including anti-atherosclerosis. Andrographolide (1) has been identified as one of the active constituents against atherosclerosis. In continuation of our drug discovery program we synthesized few novel derivatives of 1 to improve their antidyslipidemic, LDL-oxidation and antioxidant activity. The tosylated derivative 7 has been turned out to be more potent than the parent compound and comparable activity with marketed antidyslipidemic drugs.

Topics: Animals; Antioxidants; Disease Models, Animal; Diterpenes; Humans; Hyperlipidemias; Hypolipidemic Agents; Lipoproteins, LDL; Male; Molecular Structure; Oxidation-Reduction; Rats; Rats, Inbred Strains

Allopurinol, one of the most commonly used uric acid-lowering agents, can cause serious adverse events. To investigate the risk factors for allopurinol-induced adverse events, the authors enrolled 94 patients who developed allopurinol-induced adverse events and 378 controls who were randomly chosen from 1934 patients who used allopurinol but did not develop any adverse events in this retrospective case control study. Univariate analysis showed that patients who developed allopurinol-induced adverse events had more chronic kidney disease (46% vs 30%, P = .005), more hypertension (42% vs 30%, P = .036), less tumor lysis syndrome (P = .030), higher cholesterol (P = .013), and lower aspartate aminotransferase (P = .002) and alanine aminotransferase levels (P = .033) and more commonly used angiotensin receptor blockers (27% vs 15%, P = .007), colchicines (16% vs 5%, P = .010), or statins (19% vs 8%, P = .002) than those who did not. In multiple logistic regression analysis, the use of colchicines (odds ratio, 3.11; 95% confidence interval, 1.28-7.58; P = .012) and statins (2.10; 1.03-4.25; P = .041) was an independent risk factor predicting adverse events in allopurinol users. In conclusion, patients who use colchicine or statins are at significant risk for developing allopurinol-induced adverse events.

Topics: Adult; Aged; Allopurinol; Colchicine; Drug-Related Side Effects and Adverse Reactions; Female; Gout; Gout Suppressants; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypertension; Hyperuricemia; Male; Middle Aged; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Young Adult

A novel series of amide based fibrates were synthesized and evaluated for antidyslipidemic activity in triton induced hyperlipidemic rats. Interestingly, the compound 13 produced striking reduction in serum levels of total cholesterol (TC), phospholipids (PL) and triglycerides (TG). In addition, it exhibited improved lipoprotein lipase activity and found to possess moderate radical scavenging potential. The results of the above studies shows that the compounds synthesized on fibrate based pharmacophores might result in identification of new lead for dyslipidemia.

Topics: Amides; Animals; Antioxidants; Enzyme Activation; Fibric Acids; Free Radicals; Hyperlipidemias; Hypolipidemic Agents; Lipid Peroxidation; Lipoprotein Lipase; Male; Polyethylene Glycols; Rats; Structure-Activity Relationship

A series of novel benzocoumarin derivatives were synthesized and evaluated for their in vivo anti-dyslipidemic and in vitro antioxidant activities. Preliminary screening indicates compound 4 as potential lead with significant lipid lowering and antioxidant activities. The study revealed that such attempts on benzocoumarin-based pharmacophores which is a biologically important scaffold might result in identification of new lead for anti-dyslipidemia.

Topics: Animals; Coumarins; Hyperlipidemias; Hypolipidemic Agents; Rats; Structure-Activity Relationship

A series of Schiff bases have been synthesized from dicarbaldehyde of benzocoumarin, in which the reactions were regioselective and the products existed in the keto-enamine form, in which the aromaticity of the relevant ring was disrupted. The compounds were evaluated in vitro for their antioxidant and in vivo for their antidyslipidemic activity for the first time. Compounds 3 and 7 possess significant lipid lowering and antioxidant activity.

Topics: Amines; Animals; Antioxidants; Coumarins; Female; Free Radicals; Hyperlipidemias; Hypolipidemic Agents; Magnetic Resonance Spectroscopy; Molecular Structure; Rats; Schiff Bases

Hyperlipidemia can induce or aggravate renal tubulointerstitial injury. Experiments in a complex rat model with chronic glomerulonephritis and long-standing, coexisting hyperlipidemia suggested that induction of xanthine oxidase (XO), with increased oxygen radical generation, is involved in aggravation of tubulointerstitial injury. To separate the role of XO in the initial events of lipid-mediated tubulointerstitial injury, short-term experiments with diet-induced hyperlipidemia over 21 and 35 days were performed in otherwise healthy rats. XO expression in relation to the antioxidant enzymes was examined in the cortical tubulointerstitium (TIS) and proximal tubules (PT). Subsequent experiments with XO inhibition were performed, examining tubulointerstitial infiltration with ED1-positive cells and expression of adhesion molecules and monocyte chemoattractant protein-1 (MCP-1) as indicators of early injurious events. Hyperlipidemia increased XO activity in TIS by 40 and 86%, and in PT by 28 and 90% at days 21 and 35, compared with controls on regular diet. This increased activity was associated with increased reactive oxygen species. Among the antioxidant enzymes, glutathione peroxidase activity increased in TIS by 40% and in PT by 90%. Histological evaluation showed a three-fold increase in ED1-positive cells and increased MCP-1 and vascular cell adhesion molecule-1 (VCAM-1) expression at day 35 in the TIS. Inhibition of XO prevented tubulointerstitial ED1 cell infiltration, together with a decreased expression of MCP-1 and VCAM-1. These results point to an important role for XO in the early stage of hyperlipidemia-associated renal injury, mediating macrophage infiltration by a putatively redox-dependent upregulation of MCP-1 and VCAM-1.

Topics: Animals; Antioxidants; Cell Adhesion Molecules; Chemokine CCL2; Ectodysplasins; Glomerulonephritis; Hyperlipidemias; Immunohistochemistry; Kidney Tubules; Macrophages; Male; Membrane Proteins; Nephritis, Interstitial; Rats; Rats, Wistar; Reactive Oxygen Species; Tumor Necrosis Factors; Up-Regulation; Vascular Cell Adhesion Molecule-1; Xanthine Oxidase

The effects of the xanthine oxidase/hypoxanthine free radical generating system on endothelium dependent and independent relaxation were compared in aortic rings from New Zealand white rabbits and heterozygous Watanabe heritable hyperlipidemic (WHHL) rabbits with mild atherosclerosis. Studies were carried out in young (3 months) and mature (18 months) animals. Plasma cholesterol levels were significantly higher in both 3 and 18 month WHHL animals. Endothelium independent relaxation to SNP did not differ between groups. However, the attenuation of relaxation to carbachol after xanthine oxidase/hypoxanthine treatment tended to be less in WHHL. This reached significance at 18 but not 3 months. We propose that this could be due to increases in levels of endogenous scavenger enzymes in these WHHL rabbits.

Topics: Animals; Aorta, Thoracic; Arteriosclerosis; Carbachol; Cholesterol; Dose-Response Relationship, Drug; Endothelium, Vascular; Female; Free Radicals; Hyperlipidemias; Hypoxanthine; In Vitro Techniques; Male; Muscle Relaxation; Muscle, Smooth, Vascular; Nitroprusside; Rabbits; Xanthine Oxidase

Using the Intralipid lipid tolerance test we could not demonstrate any direct effect of serum triglyceride on uric acid or any influence of hyperuricaemia on triglyceride removal. This result supports previous studies suggesting that hyperuricaemia and hypertriglyceridaemia are linked through the association of obesity and alcohol excess rather than a direct cause and effect mechanism. It was possible to demonstrate significant reductions of serum triglyceride in patients with gout by reducing either their alcohol intake or body weight. Reduction of serum uric acid by probenecid had no effect on serum triglyceride or cholesterol. Similarly, allopurinol had no significant effect on serum triglyceride, but a significant fall of serum cholesterol was observed.

Topics: Alcohol Drinking; Allopurinol; Cholesterol; Gout; Humans; Hyperlipidemias; Male; Middle Aged; Obesity; Probenecid; Triglycerides; Uric Acid

Asymptomatic hyperuricemia should be treated only if the plasma uric acid levels are around 10 mg/100 ml or more on several determinations. In addition, patients on a purine-free diet who excrete more than 600 mg uric acid per 24 h should be treated. In both cases, treatment is intended to be prophylactic against gouty nephropathy. At present there is no evidence that primary hyperuricemia alone is a risk factor for early atherosclerosis and especially coronary artery disease. However, more attention should be paid to the accompanying risk factors such as obesity, hyperlipoproteinemia, diabetes mellitus and hypertension.

Topics: Allopurinol; Benzbromarone; Citrates; Coronary Disease; Gout; Humans; Hyperlipidemias; Hypertension; Hypoxanthine Phosphoribosyltransferase; Kidney Diseases; Lesch-Nyhan Syndrome; Obesity; Uric Acid

Topics: Adult; Aged; Alcohol Drinking; Allopurinol; Aspartate Aminotransferases; Body Height; Body Weight; Cholesterol; Gout; Humans; Hyperlipidemias; Liver; Male; Middle Aged; Obesity; Probenecid; Sulfobromophthalein; Triglycerides; Uric Acid

Topics: Adult; Allopurinol; Anemia; Arthritis; Benzofurans; Gout; Humans; Hyperlipidemias; Hypothyroidism; Hypoxanthines; Kidney Calculi; Male; Metabolism, Inborn Errors; Pedigree; Pentosyltransferases; Uric Acid; Uricosuric Agents

Topics: Adult; Allopurinol; Bone Diseases; Clofibrate; Diet Therapy; Dietary Carbohydrates; Femur Head Necrosis; Humans; Humerus; Hyperlipidemias; Joint Prosthesis; Knee Joint; Lipoproteins; Male; Necrosis; Prediabetic State; Triglycerides; Uric Acid

Topics: Allopurinol; Analgesics; Arteriosclerosis; Blood Platelets; Colchicine; Diabetes Complications; Gout; Halofenate; Humans; Hyperlipidemias; Hypertension; Hypoxanthines; In Vitro Techniques; Kidney Diseases; Uric Acid; Uricosuric Agents; Vascular Diseases; Xanthines

Topics: Allopurinol; Arteriosclerosis; Blood Protein Disorders; Citrates; Colchicine; Diabetes Mellitus; Diet Therapy; Gout; Humans; Hyperlipidemias; Hypertension; Kidney Calculi; Kidney Diseases; Phenylbutazone; Physical Therapy Modalities; Time Factors; Uremia; Uric Acid

Topics: Adolescent; Adrenocortical Hyperfunction; Adult; Aged; Allopurinol; Child; Diet Therapy; Female; Femur Head; Femur Head Necrosis; Hematologic Diseases; Humans; Hyperlipidemias; Lipids; Liver Diseases; Male; Metabolic Diseases; Middle Aged; Phospholipids; Uric Acid

Topics: Africa, Eastern; Animals; Arteriosclerosis; Diet; Finland; Heart Diseases; Humans; Hyperlipidemias; Japan; Milk; Myocardial Infarction; Pain; Plasmalogens; Switzerland; United States; Xanthine Oxidase

Topics: Adult; Aged; Allopurinol; Clofibrate; Consanguinity; Dietary Carbohydrates; Female; Glucose Tolerance Test; Gout; Humans; Hyperlipidemias; Lipoproteins; Male; Middle Aged; Myocardial Infarction; Pedigree; Triglycerides; Xanthomatosis

Topics: Adult; Aged; Allopurinol; Blood Protein Disorders; Blood Protein Electrophoresis; Cholesterol; Gout; Humans; Hyperlipidemias; Lipoproteins; Male; Middle Aged; Probenecid; Prognosis; Triglycerides; Uric Acid

Topics: Adult; Allopurinol; Animals; Humans; Hyperlipidemias; Male; Rabbits

Topics: Adolescent; Adult; Allopurinol; Child; Female; Glycogen Storage Disease; Glycogen Storage Disease Type I; Gout; Hepatomegaly; Humans; Hyperlipidemias; Joint Diseases; Lactates; Male; Middle Aged; Osteoporosis; Purines; Uric Acid; Uricosuric Agents

Topics: Age Factors; Aged; Allopurinol; Bone and Bones; Cardiovascular Diseases; Colchicine; Female; Gout; Humans; Hyperlipidemias; Hypertension; Kidney Diseases; Male; Probenecid; Sodium; Sulfinpyrazone; Uric Acid