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BMC Nephrology Jun 2022Asymptomatic hyperuricemia was found to be associated with increased cardiovascular disease risk but the potential benefits of urate-lowering therapy (ULT) remain... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Asymptomatic hyperuricemia was found to be associated with increased cardiovascular disease risk but the potential benefits of urate-lowering therapy (ULT) remain controversial. We conducted a systematic review and network meta-analysis (NMA) with frequentist model to estimate the efficacy and safety of ULT in asymptomatic hyperuricemia.
METHODS
MEDLINE, Embase, and Scopus were searched without language restrictions. Randomized controlled trials (RCT) of adults with asymptomatic hyperuricemia were eligible if they compared any pair of ULTs (i.e., allopurinol, febuxostat, probenecid, benzbromarone, sulfinpyrazone, rasburicase, lesinurad, and topiroxostat) and placebo or no ULT, and had outcomes of interest, including composite renal events, major adverse cardiovascular events, serum urate levels, estimated glomerular filtration rate (eGFR), systolic blood pressure, and adverse events.
RESULTS
NMA with frequentist approach was applied to estimate relative treatment effects, i.e., risk ratio (RR) and mean difference (MD). A total of 23 RCTs were eligible. NMA identified beneficial effects of ULT on composite renal events and eGFR but not for other outcomes. Allopurinol and febuxostat had significantly lower composite renal events than placebo (RR 0.39, 95% confidence interval [CI] 0.23 to 0.66, and RR 0.68, 95% CI 0.46 to 0.99, respectively). Both treatments also resulted in significantly higher eGFR than placebo (MD 3.69 ml/min/1.73 m, 95% CI 1.31 to 6.08, and MD 2.89 ml/min/1.73 m, 95% CI 0.69 to 5.09, respectively). No evidence of inconsistency was identified.
CONCLUSIONS
Evidence suggests that allopurinol and febuxostat are the ULTs of choice in reducing composite renal events and improving renal function.
TRIAL REGISTRATION
This study was registered with PROSPERO: CRD42019145908. The date of the first registration was 12 November 2019.
Topics: Adult; Allopurinol; Febuxostat; Gout; Gout Suppressants; Humans; Hyperuricemia; Network Meta-Analysis; Randomized Controlled Trials as Topic; Uric Acid
PubMed: 35739495
DOI: 10.1186/s12882-022-02850-3 -
BMJ Clinical Evidence May 2011Gout affects about 5% of men and 1% of women, with up to 80% of people experiencing a recurrent attack within 3 years. (Review)
Review
INTRODUCTION
Gout affects about 5% of men and 1% of women, with up to 80% of people experiencing a recurrent attack within 3 years.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute gout? What are the effects of treatments to prevent gout in people with prior acute episodes? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 16 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: colchicine, corticosteroids, corticotropin (ACTH), non-steroidal anti-inflammatory drugs (NSAIDs), sulfinpyrazone, xanthine oxidase inhibitors, advice to lose weight, advice to reduce alcohol intake, and advice to reduce dietary intake of purines.
Topics: Acute Disease; Adrenocorticotropic Hormone; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Gout; Gout Suppressants; Humans
PubMed: 21575286
DOI: No ID Found -
BMJ Clinical Evidence Nov 2008Gout affects about 5% of men and 1% of women, with up to 80% of people experiencing a recurrent attack within 3 years. (Review)
Review
INTRODUCTION
Gout affects about 5% of men and 1% of women, with up to 80% of people experiencing a recurrent attack within 3 years.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for acute gout? What are the effects of treatments to prevent gout in people with prior acute episodes? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: colchicine, corticosteroids, corticotrophin (ACTH), non-steroidal anti-inflammatory drugs (NSAIDs), sulfinpyrazone, xanthine oxidase inhibitors, advice to lose weight, advice to reduce alcohol intake, advice to reduce dietary intake of purines.
Topics: Acute Disease; Adrenocorticotropic Hormone; Anti-Inflammatory Agents, Non-Steroidal; Colchicine; Gout; Gout Suppressants; Humans
PubMed: 19445790
DOI: No ID Found -
American Family Physician Apr 1999Gout is a disease resulting from the deposition of urate crystals caused by the overproduction or underexcretion of uric acid. The disease is often, but not always,... (Review)
Review
Gout is a disease resulting from the deposition of urate crystals caused by the overproduction or underexcretion of uric acid. The disease is often, but not always, associated with elevated serum uric acid levels. Clinical manifestations include acute and chronic arthritis, tophi, interstitial renal disease and uric acid nephrolithiasis. The diagnosis is based on the identification of uric acid crystals in joints, tissues or body fluids. Treatment goals include termination of the acute attack, prevention of recurrent attacks and prevention of complications associated with the deposition of urate crystals in tissues. Pharmacologic management remains the mainstay of treatment. Acute attacks may be terminated with the use of nonsteroidal anti-inflammatory agents, colchicine or intra-articular injections of corticosteroids. Probenecid, sulfinpyrazone and allopurinol can be used to prevent recurrent attacks. Obesity, alcohol intake and certain foods and medications can contribute to hyperuricemia. These potentially exacerbating factors should be identified and modified.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Diagnosis, Differential; Gout; Gout Suppressants; Humans; Patient Education as Topic; Teaching Materials; Uric Acid
PubMed: 10208700
DOI: No ID Found -
British Medical Journal Aug 1978
Clinical Trial
Topics: Aspirin; Canada; Cerebrovascular Disorders; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Random Allocation; Sulfinpyrazone
PubMed: 354745
DOI: No ID Found -
British Medical Journal Jun 1979
Topics: Colchicine; Cortisone; Gout; Humans; Male; Probenecid; Sulfinpyrazone
PubMed: 466182
DOI: 10.1136/bmj.1.6179.1695 -
Canadian Medical Association Journal Feb 1973
Topics: Aspirin; Blood Platelets; Dipyridamole; Humans; Sulfinpyrazone; Thromboembolism
PubMed: 4687370
DOI: No ID Found -
International Journal For Parasitology.... Aug 2022Albendazole (ABZ) is an anthelmintic frequently used to treat haemonchosis, a common parasitosis of ruminants caused by the gastrointestinal nematode Haemonchus...
Albendazole (ABZ) is an anthelmintic frequently used to treat haemonchosis, a common parasitosis of ruminants caused by the gastrointestinal nematode Haemonchus contortus. This parasite is able to protect itself against ABZ via the formation of inactive ABZ-glycosides. The present study was designed to deepen the knowledge about the role of UDP-glycosyltransferases (UGTs) in ABZ glycosylation in H. contortus. The induction effect of phenobarbital, a classical inducer of UGTs, as well as ABZ and ABZ-sulphoxide (ABZSO, the main active metabolite of ABZ) on UGTs expression and UGT activity toward ABZ was studied ex vivo in isolated adult nematodes. The effect of three potential UGT inhibitors (5-nitrouracil, 4,6-dihydroxy-5-nitropyrimidine and sulfinpyrazone) on ABZ glycosylation was tested. Pre-incubation of nematodes with ABZ and ABZSO led to increased expression of several UGTs as well as ABZ-glycosides formation in subsequent treatment. Phenobarbital also induced UGTs expression, but did not affect ABZ biotransformation. In the nematode's subcellular fraction, sulfinpyrazone inhibited UGT activity toward ABZ, although no effect of other inhibitors was observed. The inhibitory potential of sulfinpyrazone on the formation of ABZ-glycosides was also proved ex vivo in living nematodes. The obtained results confirmed the role of UGTs in ABZ biotransformation in H. contortus adults and revealed sulfinpyrazone as a potent inhibitor of ABZ glycosylation in this parasite. The possible use of sulfinpyrazone with ABZ in combination therapy merits further research.
Topics: Albendazole; Animals; Anthelmintics; Glycosides; Glycosyltransferases; Haemonchus; Nematoda; Phenobarbital; Sheep; Sheep Diseases; Sulfinpyrazone; Uridine Diphosphate
PubMed: 35738156
DOI: 10.1016/j.ijpddr.2022.06.001 -
Journal of the American College of... Dec 1986Although many drugs have inhibitory effects on platelet function, none of them inhibits all of the mechanisms that may be involved in the various forms of thrombosis.... (Review)
Review
Although many drugs have inhibitory effects on platelet function, none of them inhibits all of the mechanisms that may be involved in the various forms of thrombosis. Choice of suitable drugs is hampered by lack of full knowledge concerning the reactions that make the major contributions to the formation of arterial thrombi at sites of repeated vessel wall injury or on atherosclerotic lesions. Drugs such as aspirin that inhibit the arachidonate pathway in platelets can only be expected to be effective against thromboembolic events in which the generation of thromboxane A2 plays a major part. If thrombin and fibrin formation are dominant, oral anticoagulant agents or heparin should be beneficial; thus, experimental evidence indicates that with repeated vessel wall injury, the formation of platelet fibrin thrombi on the vessel wall is probably influenced more by inhibitors of thrombin generation than by the subendothelial constituents such as collagen. Agents like prostacyclin that raise platelet cyclic adenosine monophosphate (AMP) levels in platelets by stimulating adenylate cyclase are potent inhibitors of the reaction of platelets to all aggregating and release-inducing stimuli, but these agents are not suitable for long-term administration. The effect of dipyridamole on platelet cyclic AMP levels is weak, and this drug may act through other effects on platelets or on other cells. Indeed, several of the drugs that have been tested in clinical trials may exert their effects through unrecognized mechanisms. Many combinations of drugs have been used to affect platelets or platelets and coagulation. This practice has been based on the theory that because several mechanisms may be involved in thrombus formation, combinations of drugs that inhibit different mechanisms may be beneficial.
Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Blood Platelets; Dextrans; Humans; Sulfinpyrazone; Thrombosis; Ticlopidine
PubMed: 2431020
DOI: 10.1016/s0735-1097(86)80004-3 -
Archives of Drug Information Mar 2011INTRODUCTION: Studies using MDCKII and LLC-PK1 cells transfected with MDR1 cDNA indicate that ciprofloxacin is not a substrate of P-glycoprotein. However, our data has...
INTRODUCTION: Studies using MDCKII and LLC-PK1 cells transfected with MDR1 cDNA indicate that ciprofloxacin is not a substrate of P-glycoprotein. However, our data has shown that transport studies done using different P-gp overexpressing cell lines (MDCKI-MDR1, MDCKII-MDR1 and L-MDR1), could lead to contradictory conclusion on whether a compound is a substrate of P-gp. The aim of our study was to determine if ciprofloxacin is indeed not a P-glycoprotein substrate using MDCKI cells transfected with human MDR1 cDNA. METHODS: Semi-quantitative RT-PCR was used to determine the mRNA level of MDR1 while Western blot was performed to determine the protein expression level of P-gp, MRP1 and MRP2 in various cells. Ciprofloxacin bidirectional transport studies were performed in MDCKI, MDCKI-MDR1, MDCKII, MDCKII-MDR1, MDCKII-MRP2, LLC-PK1, L-MRP1 and L-MDR1 cells. RESULTS: Ciprofloxacin showed net secretion in MDCKI-MDR1 but net absorption in MDCKI cells. Various P-gp inhibitors decreased the B to A and increased the A to B transport of ciprofloxacin in MDCKI-MDR1 cells while having no effect in MDCKI cells. The B to A transport of ciprofloxacin in MDCKI-MDR1 cells was not affected by non-P-gp inhibitors. In the presence of indomethacin, ciprofloxacin showed net secretion instead of net absorption in MDCKI cells while in the presence of probenecid and sulfinpyrazone, there was no net secretion and absorption. There was no difference in ciprofloxacin transport between MDCKII and MDCKII-MDR1, LLC-PK1 and L-MDR1, LLC-PK1 and L-MRP1 and MDCKII and MDCKII-MRP2. CONCLUSIONS: Transport data in MDCKI and MDCKI-MDR1 cells indicate that ciprofloxacin is a substrate of P-gp but data from MDCKII, MDCKII-MDR1, LLC-PK1 and L-MDR1 cells indicate that ciprofloxacin is not a substrate of P-gp. Vinblastine, a well-known P-gp substrate, also did not show differences between LLC-PK1 and L-MDR1 cells. Further studies need to be performed to characterize these P-gp overexpressing cell lines and the transport of ciprofloxacin.
PubMed: 21572514
DOI: 10.1111/j.1753-5174.2010.00032.x