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https://www.readbyqxmd.com/read/28201850/novel-treatment-strategies-for-primary-biliary-cholangitis
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28065762/characterisation-of-early-changes-in-ovine-cln5-and-cln6-batten-disease-neural-cultures-for-the-rapid-screening-of-therapeutics
#13
Hannah L Best, Nicole J Neverman, Hollie E Wicky, Nadia L Mitchell, Beulah Leitch, Stephanie M Hughes
Batten disease (neuronal ceroid lipofuscinosis) refers to a group of neurodegenerative lysosomal storage diseases predominantly affecting children. There are currently no effective treatments, and the functions of many of the associated gene products are unknown. Here we characterise fetal neural cultures from two genetically distinct sheep forms of Batten disease, with mutations in the lysosomal protein encoding gene CLN5 and endoplasmic reticulum membrane protein encoding gene CLN6, respectively. We found similar reductions in autophagy, acidic organelles and synaptic recycling in both forms compared to unaffected cells...
January 5, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28063740/high-density-lipoproteins-biology-epidemiology-and-clinical-management
#14
REVIEW
Hong Y Choi, Anouar Hafiane, Adel Schwertani, Jacques Genest
High-density lipoproteins (HDLs) have multiple pleiotropic effects against arteriosclerosis. Most are independent of the cholesterol mass within HDL particles. Yet, HDL cholesterol (HDL-C) remains a biomarker to assess cardiovascular risk. Whereas the epidemiological association between HDL-C and cardiovascular risk is strong, graded and coherent across populations, Mendelian randomization studies cast doubt on whether HDL-C is causally related to atherosclerotic cardiovascular disease. The apparent failure of HDL-C-raising therapies (fibrates, niacin, and cholesteryl ester transfer protein inhibitors) raises questions about the HDL-C hypothesis...
October 20, 2016: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/28049491/fenofibrate-in-the-management-of-abdominal-aortic-aneurysm-fame-study-protocol-for-a-randomised-controlled-trial
#15
Sophie E Rowbotham, Doug Cavaye, Rene Jaeggi, Jason S Jenkins, Corey S Moran, Joseph V Moxon, Jenna L Pinchbeck, Frank Quigley, Christopher M Reid, Jonathan Golledge
BACKGROUND: Abdominal aortic aneurysm (AAA) is a slowly progressive destructive process of the main abdominal artery. Experimental studies indicate that fibrates exert beneficial effects on AAAs by mechanisms involving both serum lipid modification and favourable changes to the AAA wall. METHODS/DESIGN: Fenofibrate in the management of AbdoMinal aortic anEurysm (FAME) is a multicentre, randomised, double-blind, placebo-controlled clinical trial to assess the effect of orally administered therapy with fenofibrate on key pathological markers of AAA in patients undergoing open AAA repair...
January 4, 2017: Trials
https://www.readbyqxmd.com/read/28036029/fenofibrate-therapy-restores-antioxidant-protection-and-improves-myocardial-insulin-resistance-in-a-rat-model-of-metabolic-syndrome-and-myocardial-ischemia-the-role-of-angiotensin-ii
#16
Luz Ibarra-Lara, María Sánchez-Aguilar, Alicia Sánchez-Mendoza, Leonardo Del Valle-Mondragón, Elizabeth Soria-Castro, Elizabeth Carreón-Torres, Eulises Díaz-Díaz, Héctor Vázquez-Meza, Verónica Guarner-Lans, María Esther Rubio-Ruiz
Renin-angiotensin system (RAS) activation promotes oxidative stress which increases the risk of cardiac dysfunction in metabolic syndrome (MetS) and favors local insulin resistance. Fibrates regulate RAS improving MetS, type-2 diabetes and cardiovascular diseases. We studied the effect of fenofibrate treatment on the myocardic signaling pathway of Angiotensin II (Ang II)/Angiotensin II type 1 receptor (AT1) and its relationship with oxidative stress and myocardial insulin resistance in MetS rats under heart ischemia...
December 28, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27988827/atherogenic-dyslipidemia-remission-1%C3%A2-year-after-bariatric-surgery
#17
Elisenda Climent, David Benaiges, Juan Pedro-Botet, Juana A Flores-Le Roux, Jose M Ramón, Montserrat Villatoro, Laia Fontané, Juan J Chillarón, Albert Goday
PURPOSE: Given the lack of evidence of the effect of bariatric surgery (BS) on atherogenic dyslipidemia (AD), which is a characteristic of obese subjects, this study aimed to describe the remission rate of AD 1 year after BS in severely obese patients. MATERIALS AND METHODS: A non-randomised, prospective cohort study was conducted in patients undergoing laparoscopic Roux-en-Y gastric bypass or laparoscopic sleeve gastrectomy with a 1-year follow-up. AD was defined as triglycerides ≥1...
December 17, 2016: Obesity Surgery
https://www.readbyqxmd.com/read/27987461/modelling-the-photochemical-attenuation-pathways-of-the-fibrate-drug-gemfibrozil-in-surface-waters
#18
Debora Fabbri, Valter Maurino, Marco Minella, Claudio Minero, Davide Vione
Gemfibrozil (GFZ) is a relatively persistent pollutant in surface-water environments and it is rather recalcitrant to biological degradation. The GFZ photochemical lifetimes are relatively short in shallow waters with low levels of dissolved organic carbon (DOC), but they can reach the month-year range in deep and high-DOC waters. The main reason is that GFZ undergoes negligible reaction with singlet oxygen or degradation sensitised by the triplet states of chromophoric dissolved organic matter, which are the usually prevalent photochemical pathways in deep and high-DOC sunlit waters...
March 2017: Chemosphere
https://www.readbyqxmd.com/read/27979321/analysis-of-the-cochrane-review-fibrates-for-secondary-prevention-of-cardiovascular-disease-and-stroke
#19
Gilberto Pires da Rosa, Diogo Libânio, Luís Filipe Azevedo
The influence of fibrates on cardiovascular risk has been the focus of several clinical trials. This Cochrane Collaboration Systematic Review evaluated the efficacy of fibrates for secondary prevention of cardiovascular events and stroke, analyzing 13 randomized controlled trials, in a total of 16 112 participants with a history of cardiovascular disease. Fibrates showed a protective effect for the composite outcome of non-fatal stroke, non-fatal myocardial infarction (MI) and vascular death, mainly due to reduction in the risk of non-fatal or fatal MI...
January 2017: Portuguese Journal of Cardiology: An Official Journal of the Portuguese Society of Cardiology
https://www.readbyqxmd.com/read/27957241/recent-advances-in-the-diagnosis-and-treatment-of-primary-biliary-cholangitis
#20
REVIEW
Ying-Qiu Huang
Primary biliary cholangitis (PBC), formerly referred to as primary biliary cirrhosis, is an infrequent progressive intrahepatic cholestatic autoimmune illness that can evolve into hepatic fibrosis, hepatic cirrhosis, hepatic failure, and, in some cases, hepatocellular carcinoma. The disease itself is characterized by T-lymphocyte-mediated chronic non-suppurative destructive cholangitis and elevated serum levels of extremely specific anti-mitochondrial autoantibodies (AMAs). In this article, we will not only review epidemiology, risk factors, natural history, predictive scores, radiologic approaches (e...
November 28, 2016: World Journal of Hepatology
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