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https://www.readbyqxmd.com/read/28302902/risk-of-febuxostat-associated-myopathy-in-patients-with-ckd
#1
Chung-Te Liu, Chun-You Chen, Chien-Yi Hsu, Po-Hsun Huang, Feng-Yen Lin, Jaw-Wen Chen, Shing-Jong Lin
BACKGROUND AND OBJECTIVES: Febuxostat, a nonpurine xanthine oxidase inhibitor, is widely used to treat hyperuricemia. Although febuxostat-associated rhabdomyolysis was reported in some patients with CKD, the association between CKD and febuxostat-associated myopathy remains uncertain. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our retrospective cohort study included 1332 patients using febuxostat in Taipei Medical University-Wanfang Hospital from February of 2014 to January of 2016...
March 16, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28300080/hypertriglyceridaemia-and-risk-of-coronary-artery-disease
#2
REVIEW
Željko Reiner
An elevated serum level of LDL cholesterol is a well-known risk factor for cardiovascular disease (CVD), but the role of elevated triglyceride levels is debated. Controversies regarding hypertriglyceridaemia as an independent risk factor for CVD have occurred partly because elevated triglyceride levels are often a component of atherogenic dyslipidaemia - they are associated with decreased levels of HDL cholesterol and increased levels of small dense LDL particles, which are highly atherogenic. Findings from several large studies indicate that elevated levels of triglycerides (either fasting or nonfasting) or, more specifically, triglyceride-rich lipoproteins and their remnants, are independently associated with increased risk of CVD...
March 16, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28263783/establishment-of-a-novel-mouse-model-for-pioglitazone-induced-skeletal-muscle-injury
#3
Sho Akai, Shingo Oda, Tsuyoshi Yokoi
Skeletal muscle (SKM) injury is one of the major safety concerns in risk assessment for drug development. However, no appropriate pre-clinical animal model exists to evaluate drug-induced SKM injury except that caused by fibrates and statins. Thiazolidinedione, a PPARγ agonistic drug for type 2 diabetes mellitus, is widely used clinically but can induce adverse effects such as hepatotoxicity and SKM injury, as has been reported in recent decades. Moreover, thiazolidinedione-induced SKM injury has only been reported in humans, and no evidence of SKM injury has been observed in rodents...
March 2, 2017: Toxicology
https://www.readbyqxmd.com/read/28262189/hypercholesterolemia-as-a-risk-factor-for-cardiovascular-disease-current-controversial-therapeutic-management
#4
REVIEW
Arturo Zárate, Leticia Manuel-Apolinar, Renata Saucedo, Marcelino Hernández-Valencia, Lourdes Basurto
Cholesterol is a precursor of steroid hormones and an essential component of the cell membrane; however, altered regulation of the synthesis, absorption and excretion of cholesterol predispose to cardiovascular diseases of atherosclerotic origin. Despite the recognition of historical events for 200 years starting with Chevreul naming "cholesterine"; later on, Lobstein coining the term atherosclerosis and Marchand introducing it, Anichkov identifying cholesterol in atheromatous plaque, and Brown and Goldstein discovering LDL receptor (r-LDL), as well as the emergence of different drugs such as fibrates, statins and cetrapibs during this decade promising to increase HDL, and the most recent, ezetimibe and anti-PCSK9 to inhibit the degradation of r-LDL, morbidity has not been reduced in cardiovascular disease...
October 2016: Archives of Medical Research
https://www.readbyqxmd.com/read/28251701/molecular-effect-of-fenofibrate-on-pbmc-gene-transcription-related-to-lipid-metabolism-in-metabolic-syndrome-patients
#5
I Moreno-Indias, F J Tinahones, M Clemente-Postigo, D Castellano-Castillo, J C Fernández-García, M Macias-Gonzalez, M I Queipo-Ortuño, F Cardona
BACKGROUND: Both fasting and postprandial hypertriglyceridaemia are considered independent risk factors for atherosclerosis. Treatment of hypertriglyceridaemia is based on fibrates, which activate the peroxisome proliferator-activated receptor alpha (PPARα). However, the metabolic pathways that activate or inhibit fibrates, and how the postprandial triglyceride levels are modified, have not yet been fully described. Accordingly, the aim of this study was to determine the feasibility of peripheral blood mononuclear cells (PBMC) to study the effects of fenofibrate in patients with the metabolic syndrome...
March 2, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28248971/clofibrate-inhibits-the-umami-savory-taste-of-glutamate
#6
Matthew Kochem, Paul A S Breslin
In humans, umami taste can increase the palatability of foods rich in the amino acids glutamate and aspartate and the 5'-ribonucleotides IMP and GMP. Umami taste is transduced, in part, by T1R1-T1R3, a heteromeric G-protein coupled receptor. Umami perception is inhibited by sodium lactisole, which binds to the T1R3 subunit in vitro. Lactisole is structurally similar to the fibrate drugs. Clofibric acid, a lipid lowering drug, also binds the T1R3 subunit in vitro. The purpose of this study was to determine whether clofibric acid inhibits the umami taste of glutamate in human subjects...
2017: PloS One
https://www.readbyqxmd.com/read/28242176/2017-taiwan-lipid-guidelines-for-high-risk-patients
#7
REVIEW
Yi-Heng Li, Kwo-Chang Ueng, Jiann-Shing Jeng, Min-Ji Charng, Tsung-Hsien Lin, Kuo-Liong Chien, Chih-Yuan Wang, Ting-Hsing Chao, Ping-Yen Liu, Cheng-Huang Su, Shih-Chieh Chien, Chia-Wei Liou, Sung-Chun Tang, Chun-Chuan Lee, Tse-Ya Yu, Jaw-Wen Chen, Chau-Chung Wu, Hung-I Yeh
In Taiwan, the prevalence of hyperlipidemia increased due to lifestyle and dietary habit changes. Low density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) are all significant predicting factors of coronary artery disease in Taiwan. We recognized that lipid control is especially important in patients with existed atherosclerotic cardiovascular diseases (ASCVD), including coronary artery disease (CAD), ischemic stroke and peripheral arterial disease (PAD). Because the risk of ASCVD is high in patients with diabetes mellitus (DM), chronic kidney disease (CKD) and familial hypercholesterolemia (FH), lipid control is also necessary in these patients...
February 24, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28228373/statins-and-fibrates-for-diabetic-retinopathy-protocol-for-a-systematic-review
#8
Vania Mozetic, Carolina Gomes Freitas, Rachel Riera
BACKGROUND: Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus, and more than 75% of patients who have had diabetes for more than 20 years will have some degree of DR. This disease is highly destructive to self-esteem and puts a high burden on public health and pension systems due to the effects that it has on people of working age. The current mainstay of treatment is laser photocoagulation, which causes impairment of vision and discomfort to patients...
February 22, 2017: JMIR Research Protocols
https://www.readbyqxmd.com/read/28201850/novel-treatment-strategies-for-primary-biliary-cholangitis
#9
Albert Parés
Despite the presumed immunological pathogenesis of primary biliary cholangitis, no clear or even harmful consequences have resulted from treatments designed to modify the immunological condition. Ursodeoxycholic acid (13-16 mg/kg/d) has, however, clear favorable effects that not only improve biochemical cholestasis, but also delay histological progression. Long-term treatment with ursodeoxycholic acid is associated with excellent transplant-free survival in cases showing a biochemical response at 1 year. Data on the effects of obeticholic acid and fibrates are encouraging...
February 2017: Seminars in Liver Disease
https://www.readbyqxmd.com/read/28195199/pemafibrate-a-novel-selective-peroxisome-proliferator-activated-receptor-alpha-modulator-improves-the-pathogenesis-in-a-rodent-model-of-nonalcoholic-steatohepatitis
#10
Yasushi Honda, Takaomi Kessoku, Yuji Ogawa, Wataru Tomeno, Kento Imajo, Koji Fujita, Masato Yoneda, Toshiaki Takizawa, Satoru Saito, Yoji Nagashima, Atsushi Nakajima
The efficacy of peroxisome proliferator-activated receptor α-agonists (e.g., fibrates) against nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) in humans is not known. Pemafibrate is a novel selective peroxisome proliferator-activated receptor α modulator that can maximize the beneficial effects and minimize the adverse effects of fibrates used currently. In a phase-2 study, pemafibrate was shown to improve liver dysfunction in patients with dyslipidaemia. In the present study, we first investigated the effect of pemafibrate on rodent models of NASH...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28191471/lipids-a-suitable-therapeutic-target-in-diabetic-neuropathy
#11
REVIEW
M C Perez-Matos, M C Morales-Alvarez, C O Mendivil
Diabetic polyneuropathy (DPN) encompasses multiple syndromes with a common pathogenesis. Glycemic control shows a limited correlation with DPN, arguing in favor of major involvement of other factors, one of which is alterations of lipid and lipoprotein metabolism. Consistent associations have been found between plasma triglycerides/remnant lipoproteins and the risk of DPN. Studies in cultured nerve tissue or in murine models of diabetes have unveiled mechanisms linking lipid metabolism to DPN. Deficient insulin action increases fatty acids flux to nerve cells, inducing mitochondrial dysfunction, anomalous protein kinase C signaling, and perturbations in the physicochemical properties of the plasma membrane...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28179883/new-microrna-biomarkers-for-drug-induced-steatosis-and-their-potential-to-predict-the-contribution-of-drugs-to-non-alcoholic-fatty-liver-disease
#12
Mireia López-Riera, Isabel Conde, Laia Tolosa, Ángela Zaragoza, José V Castell, María J Gómez-Lechón, Ramiro Jover
Background and Aims: Drug-induced steatosis is a major reason for drug failure in clinical trials and post-marketing withdrawal; and therefore, predictive biomarkers are essential. These could be particularly relevant in non-alcoholic fatty liver disease (NAFLD), where most patients show features of the metabolic syndrome and are prescribed with combined chronic therapies, which can contribute to fatty liver. However, specific biomarkers to assess the contribution of drugs to NAFLD are lacking. We aimed to find microRNAs (miRNAs) responsive to steatotic drugs and to investigate if they could become circulating biomarkers for drug-induced steatosis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28153024/comparison-of-the-effects-of-fibrates-versus-statins-on-plasma-lipoprotein-a-concentrations-a-systematic-review-and-meta-analysis-of-head-to-head-randomized-controlled-trials
#13
Amirhossein Sahebkar, Luis E Simental-Mendía, Gerald F Watts, Maria-Corina Serban, Maciej Banach
BACKGROUND: Raised plasma lipoprotein(a) (Lp(a)) concentration is an independent and causal risk factor for atherosclerotic cardiovascular disease. Several types of pharmacological approaches are under evaluation for their potential to reduce plasma Lp(a) levels. There is suggestive evidence that statins and fibrates, two frequently employed lipid-lowering drugs, can lower plasma Lp(a). The present study aims to compare the efficacy of fibrates and statins in reducing plasma concentrations of Lp(a) using a meta-analysis of randomized head-to-head trials...
February 3, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28139735/nutritional-background-changes-the-hypolipidemic-effects-of-fenofibrate-in-nile-tilapia-oreochromis-niloticus
#14
Li-Jun Ning, An-Yuan He, Dong-Liang Lu, Jia-Min Li, Fang Qiao, Dong-Liang Li, Mei-Ling Zhang, Li-Qiao Chen, Zhen-Yu Du
Peroxisome proliferation activated receptor α (PPARα) is an important transcriptional regulator of lipid metabolism and is activated by high-fat diet (HFD) and fibrates in mammals. However, whether nutritional background affects PPARα activation and the hypolipidemic effects of PPARα ligands have not been investigated in fish. In the present two-phase study of Nile tilapia (Oreochromis niloticus), fish were first fed a HFD (13% fat) or low-fat diet (LFD; 1% fat) diet for 10 weeks, and then fish from the first phase were fed the HFD or LFD supplemented with 200 mg/kg body weight fenofibrate for 4 weeks...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28131079/-1-h-nmr-based-metabolomics-reveals-sub-lethal-toxicity-of-a-mixture-of-diabetic-and-lipid-regulating-pharmaceuticals-on-amphibian-larvae
#15
Steven D Melvin, Leesa J Habener, Frederic D L Leusch, Anthony R Carroll
Pharmaceuticals are widely used for the treatment of various physical and psychological ailments. Due to incomplete removal during sewage treatment many pharmaceuticals are frequently detected in aquatic waterways at trace concentrations. The diversity of pharmaceutical contaminants and potential for complex mixtures to occur makes it very difficult to predict the toxicity of these compounds on wildlife, and robust methods are therefore needed to explore sub-lethal effects. Metabolic syndrome is one of the most widespread health concerns currently facing the human population, and various drugs, including anti-diabetic medications and lipid- and cholesterol-lowering fibrates and statins, are widely prescribed as treatment...
March 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28128058/apolipoprotein-a-antisense-oligonucleotides-a-new-treatment-option-for-lowering-elevated-lipoprotein-a
#16
Julia Schreml, Ioanna Gouni-Berthold
BACKGROUND: Lipoprotein(a) [Lp(a)] is a particle similar to LDL that contains an additional protein called apolipoprotein(a) [apo(a)]. Recent epidemiologic and Mendelian randomization studies have provided evidence that Lp(a) may be causally related to the pathogenesis of atherosclerosis and cardiovascular disease (CVD). While the risk association between Lp(a) concentrations and CVD is weak it seems to be continuous in shape and without an obvious threshold for Lp(a) levels. METHODS: Circulating concentrations of Lp(a) are genetically determined and desirable levels are < 50 mg/dl...
January 25, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28098593/familial-dysbetalipoproteinemia-an-underdiagnosed-lipid-disorder
#17
Charlotte Koopal, A David Marais, Frank L J Visseren
PURPOSE OF REVIEW: To review pathophysiological, epidemiological and clinical aspects of familial dysbetalipoproteinemia; a model disease for remnant metabolism and remnant-associated cardiovascular risk. RECENT FINDINGS: Familial dysbetalipoproteinemia is characterized by remnant accumulation caused by impaired remnant clearance, and premature cardiovascular disease. Most familial dysbetalipoproteinemia patients are homozygous for apolipoprotein ε2, which is associated with decreased binding of apolipoprotein E to the LDL receptor...
January 16, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/28098353/the-role-of-various-peroxisome-proliferator-activated-receptors-and-their-ligands-in-clinical-practice
#18
REVIEW
Giuseppe Derosa, Amirhossein Sahebkar, Pamela Maffioli
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors involved in several physiological processes including modulation of cellular differentiation, development, metabolism of carbohydrates, lipids, proteins, and tumorigenesis. The aim of this review is to examine how different PPAR ligands act, and discuss their use in clinical practice. PPAR ligands have a lot of effects and applications in clinical practice. Some PPAR ligands such as fibrates (PPAR-α ligands) are currently used for the treatment of dyslipidemia, while pioglitazone and rosiglitazone (PPAR-γ ligands) are anti-diabetic and insulin-sensitizing agents...
January 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28097454/in-vitro-cytogenetic-toxicity-of-bezafibrate-in-human-peripheral-blood-lymphocytes
#19
M Topaktas, N E Kafkas, S Sadighazadi, E S Istifli
Bezafibrate (BF) is a peroxisome proliferator-activated receptor (PPAR) agonist used as a lipid-lowering agent to treat both the familial or acquired combined forms of hyperlipidemia. BF is the only available fibrate drug that acts on all PPAR subtypes of α, β, and δ. Although there are studies that indicate a genotoxic potential associated with the use of fibrates, to our knowledge, the genotoxicity of BF in human peripheral blood lymphocytes has not been studied. In the present study, the genotoxic potential of BF was evaluated using chromosome aberration (CA) and micronucleus (MN) assays in peripheral blood lymphocytes of healthy human subjects...
January 17, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28088358/the-peroxisome-proliferator-activated-receptor-alpha-agonist-fenofibrate-attenuates-alcohol-self-administration-in-rats
#20
Colin N Haile, Therese A Kosten
Fibrates are a class of medications used to treat hypercholesterolemia and dyslipidemia that target nuclear peroxisome proliferator-activated receptors (PPARs). Studies have shown the PPARα agonist fenofibrate decreases voluntary EtOH consumption however its impact on the reinforcing and motivational effects of EtOH is unknown. We evaluated the ability of fenofibrate (25, 50 and 100 mg/kg), to alter EtOH (10%, w/v) and sucrose (2%, w/v) operant self-administration in rats under a FR2 schedule of reinforcement over four days and under a progressive ratio (PR) schedule on day five of treatment...
January 11, 2017: Neuropharmacology
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