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https://www.readbyqxmd.com/read/28088358/the-peroxisome-proliferator-activated-receptor-alpha-agonist-fenofibrate-attenuates-alcohol-self-administration-in-rats
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/27918198/ppar%C3%AE-dependent-increase-of-mouse-urine-output-by-gemfibrozil-and-fenofibrate
#10
Danjun Song, Min Luo, Manyun Dai, Shizhong Bu, Weihua Wang, Burong Zhang, Frank J Gonzalez, Aiming Liu
While gemfibrozil and fenofibrate are prescribed for anti-dyslipidemia treatment, a rational basis for the use of these drugs for treatment of dyslipidemia with concurrent metabolic syndrome has not been established. In this study, wild-type and Pparα-null mice were fed gemfibrozil- or fenofibrate-containing diets for 14 days. Urine output (24 h) was monitored, and urine, serum, and liver and kidney tissues were subjected to toxicity assessment. A 2-month challenge followed by a 2-week wash-out was performed for gemfibrozil to determine urine output and the potential toxicity...
September 6, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27916646/roles-of-peroxisome-proliferator-activated-receptor-%C3%AE-%C3%AE-in-skeletal-muscle-physiology
#11
REVIEW
Ravikumar Manickam, Walter Wahli
More than two decades of studying Peroxisome Proliferator-Activated Receptors (PPARs) has led to an understanding of their implications in various physiological processes that are key for health and disease. All three PPAR isotypes, PPARα, PPARβ/δ, and PPARγ, are activated by a variety of molecules, including fatty acids, eicosanoids and phospholipids, and regulate a spectrum of genes involved in development, lipid and carbohydrate metabolism, inflammation, and proliferation and differentiation of many cell types in different tissues...
December 2, 2016: Biochimie
https://www.readbyqxmd.com/read/27888906/-lipid-lowering-drugs-and-pcsk9
#12
Jesús Millán Núñez-Cortés, José M Mostaza Prieto
PCSK9 is a protease, synthesized mainly in the liver, which promotes the hepatic degradation of the LDL receptor and consequently decreases LDL receptor density and clearance of LDL particles. Statins inhibit HMG-CoA-reductase activity, an enzyme that catalyses an important step in hepatic cholesterol biosynthesis. The decrease of the hepatic intracellular cholesterol pool produced by these drugs upregulates the activity of the SREBP2 transcription factor, which subsequently stimulates the expression of the LDL receptor gene, an effect that is followed by an increase in the serum concentration of PCSK9...
May 2016: Clínica e Investigación en Arteriosclerosis
https://www.readbyqxmd.com/read/27888753/gastrointestinal-bleeding-and-intracranial-hemorrhage-in-concomitant-users-of-warfarin-and-antihyperlipidemics
#13
Charles E Leonard, Colleen M Brensinger, Warren B Bilker, Stephen E Kimmel, Xu Han, Young Hee Nam, Joshua J Gagne, Margaret J Mangaali, Sean Hennessy
BACKGROUND: Drug interactions, particularly those involving warfarin, are a major clinical and public health problem. Minimizing serious bleeding caused by anticoagulants is a recent major focus of the United States (US) Department of Health and Human Services. This study quantified the risk of gastrointestinal bleeding (GIB) and intracranial hemorrhage (ICH) among concomitant users of warfarin and individual antihyperlipidemics. METHODS: The authors conducted a high-dimensional propensity score-adjusted cohort study of new concomitant users of warfarin and an antihyperlipidemic, among US Medicaid beneficiaries from five states during 1999-2011...
February 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/27871028/microstructure-analysis-method-for-evaluating-degenerated-intervertebral-disc-tissue
#14
Andrea Friedmann, Felix Goehre, Christopher Ludtka, Thomas Mendel, Hans-Joerg Meisel, Andreas Heilmann, Stefan Schwan
Degeneration of intervertebral disc (IVD) tissue is characterized by several structural changes that result in variations in disc physiology and loss of biomechanical function. The complex process of degeneration exhibits highly intercorrelated biomechanical, biochemical, and cellular interactions. There is currently some understanding of the cellular changes in degenerated intervertebral disc tissue, but microstructural changes and deterioration of the tissue matrix has previously been rarely explored. In this work, sequestered IVD tissue was successfully characterized using histology, light microscopy, and scanning electron microscopy (SEM) to quantitatively evaluate parameters of interest for intervertebral disc degeneration (IDD) such as delamination of the collagenous matrix, cell density, cell size, and extra cellular matrix (ECM) thickness...
October 21, 2016: Micron: the International Research and Review Journal for Microscopy
https://www.readbyqxmd.com/read/27864787/glycaemic-effects-of-non-statin-lipid-lowering-therapies
#15
REVIEW
Patrick D Collins, Naveed Sattar
Since the publication of the JUPITER trial, attention has been focused on the adverse glycemic effects of statin therapy. Although the modest increase in the risk of new diabetes mellitus is outweighed by the reduction in cardiovascular events for statins, emerging biochemical and genetic links between lipid metabolism and glycemic control raise the prospect of a broader diabetogenic effect of lipid-lowering therapies. For the novel and powerful PCSK9-inhibitor class available evidence does not support a major glycaemic effect with the results of large scale trials awaited although preliminary genetic data does suggest a link...
December 2016: Current Cardiology Reports
https://www.readbyqxmd.com/read/27864237/effect-of-selected-clinical-trial-publication-on-adjunctive-nonstatin-medication-prescribing-in-the-veterans-health-administration-system
#16
Krystal S Titus-Rains, Matthew A Cantrell, Jason A Egge, Bruce Alexander, Robert F Shaw, Tami R Argo
PURPOSE: The question of whether publication of selected clinical trials is temporally followed by changes in prescribing of adjunctive lipid-lowering medications was evaluated. METHODS: In this retrospective preanalysis and postanalysis, Veterans Health Administration (VHA) patients 18 years or older who received a new or renewed order for any lipid-lowering medication between April 2, 2004, and September 2, 2014, were included. This period was chosen based on the publication dates of three trials investigating the efficacy of nonstatin medications: Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia (ENHANCE, April 3, 2008), Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus (ACCORD Lipid, March 14, 2010), and Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy (AIM-HIGH, December 15, 2011)...
December 1, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27849333/fibrates-for-primary-prevention-of-cardiovascular-disease-events
#17
REVIEW
Tobias Jakob, Alain J Nordmann, Stefan Schandelmaier, Ignacio Ferreira-González, Matthias Briel
BACKGROUND: Fibrates are effective for modifying atherogenic dyslipidaemia, and particularly for lowering serum triglycerides. However, evidence that fibrates reduce mortality and morbidity associated with cardiovascular disease (CVD), or overall mortality and morbidity, in the primary prevention of CVD is lacking. OBJECTIVES: This Cochrane Review and meta-analysis aimed to evaluate the clinical benefits and harms of fibrates versus placebo or usual care or fibrates plus other lipid-modifying drugs versus other lipid-modifying drugs alone for the primary prevention of cardiovascular disease (CVD) morbidity and mortality...
16, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27846381/mechanistic-insights-into-pathological-changes-in-the-diabetic-retina-implications-for-targeting-diabetic-retinopathy
#18
REVIEW
Sayon Roy, Timothy S Kern, Brian Song, Caren Stuebe
Increasing evidence points to inflammation as one of the key players in diabetes-mediating adverse effects to the neuronal and vascular components of the retina. Sustained inflammation induces biochemical and molecular changes, ultimately contributing to retinal complications and vision loss in diabetic retinopathy. In this review, we describe changes involving metabolic abnormalities secondary to hyperglycemia, oxidative stress, and activation of transcription factors, together with neuroglial alterations in the diabetic retina...
January 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/27829582/postprandial-hyperlipidemia-and-remnant-lipoproteins
#19
Daisaku Masuda, Shizuya Yamashita
Fasting hypertriglyceridemia is positively associated with the morbidity of coronary heart disease (CHD), and postprandial (non-fasting) hypertriglyceridemia is also correlated with the risk status for CHD, which is related to the increase in chylomicron (CM) remnant lipoproteins produced from the intestine. CM remnant particles, as well as oxidized low density lipoprotein (LDL) or very low density lipoprotein (VLDL) remnants, are highly atherogenic and act by enhancing systemic inflammation, platelet activation, coagulation, thrombus formation, and macrophage foam cell formation...
November 8, 2016: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/27822076/residual-cardiovascular-risk-in-patients-who-received-lipid-lowering-treatment-in-a-real-life-setting-retrospective-study
#20
Valentina Perrone, Diego Sangiorgi, Stefano Buda, Luca Degli Esposti
INTRODUCTION: The objective of this study was twofold: 1) to assess the residual cardiovascular (CV) risk among patients treated with statins according to guidelines and at the recommended dosages; and 2) to assess the difference, if any, in the frequency of CV events when patients were treated with other lipid-lowering agents alongside statins. METHODS: A retrospective observational study including one local health unit was conducted. Administrative databases were linked to laboratory test database in order to collect cholesterol values at baseline...
2016: ClinicoEconomics and Outcomes Research: CEOR
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