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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/28079205/reversible-control-of-solubility-using-functionalized-nanoparticles
#2
Samir A Kulkarni, Allan S Myerson
The paper provides a novel method for the reversible control of solubility by use of functionalized nanoparticles. The nanoparticles are functionalized with functional groups that can act as a co-solvent or anti-solvent and thus can induce either dissolution or crystallization. The process is reversible, as the solution will go back to its original state when the nanoparticles are removed. The use of magnetic nanoparticles facilitates this reversibility. Reductions in solubility (and thus crystallization) were demonstrated for d-mannitol-water, sodium chloride-water and fenofibrate-ethyl acetate systems...
January 12, 2017: Chemical Communications: Chem Comm
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
#3
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/28058034/retrospective-analysis-of-the-effects-of-a-highly-standardized-mixture-of-berberis-aristata-silybum-marianum-and-monacolins-k-and-ka-in-patients-with-dyslipidemia
#4
Francesco Di Pierro, Pietro Putignano, Tarcisio Ferrara, Carmela Raiola, Giuliana Rapacioli, Nicola Villanova
BACKGROUND: Berberis aristata, because of its berberine content, and Monascus purpureus fermented rice, because of the presence of monacolins (naturally derived statins), are widely investigated food-grade ingredients used to formulate cholesterol-lowering supplements. Although they are extensively used, berberine is poorly absorbed and monacolins are poorly chemically characterized, not standardized, and possibly contaminated with toxic compounds. Silymarin is reported to enhance berberine absorption, while Monakopure™-K20 (MK-20) is a highly standardized red yeast rice containing monacolins K and KA in the ratio of 1:1 but not secondary monacolins, dehydromonacolins, or citrinin...
2017: Clinical Pharmacology: Advances and Applications
https://www.readbyqxmd.com/read/28049491/fenofibrate-in-the-management-of-abdominal-aortic-aneurysm-fame-study-protocol-for-a-randomised-controlled-trial
#5
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/28043905/association-of-liver-injury-from-specific-drugs-or-groups-of-drugs-with-polymorphisms-in-hla-and-other-genes-in-a-genome-wide-association-study
#6
Paola Nicoletti, Guruprasad P Aithal, Einar S Bjornsson, Raul J Andrade, Ashley Sawle, Marco Arrese, Huiman X Barnhart, Emmanuelle Bondon-Guitton, Paul H Hayashi, Fernando Bessone, Alfonso Carvajal, Ingolf Cascorbi, Elizabeth T Cirulli, Naga Chalasani, Anita Conforti, Sally A Coulthard, Mark J Daly, Christopher P Day, John F Dillon, Robert J Fontana, Jane I Grove, Pär Hallberg, Nelia Hernández, Luisa Ibáñez, Gerd A Kullak-Ublick, Tarja Laitinen, Dominique Larrey, M Isabel Lucena, Anke H Maitland-van der Zee, Jennifer H Martin, Mariam Molokhia, Munir Pirmohamed, Elizabeth E Powell, Shengying Qin, Jose Serrano, Camilla Stephens, Andrew Stolz, Mia Wadelius, Paul B Watkins, Aris Floratos, Yufeng Shen, Matthew R Nelson, Thomas J Urban, Ann K Daly
BACKGROUND & AIMS: We performed a genome-wide association study (GWAS) to identify genetic risk factors for drug-induced liver injury (DILI) from licensed drugs without previously reported genetic risk factors. METHODS: We performed a GWAS of 862 persons with DILI and 10588 population-matched controls. The first set of cases was recruited prior to May 2009 in Europe (n=137) or the USA (n=274). The second set of cases were identified from May 2009 through May 2013 from international collaborative studies performed in Europe, the USA and South America...
December 30, 2016: Gastroenterology
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
#7
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/28030716/association-of-fenofibrate-therapy-with-long-term-cardiovascular-risk-in-statin-treated-patients-with-type-2-diabetes
#8
Marshall B Elam, Henry N Ginsberg, Laura C Lovato, Marshall Corson, Joseph Largay, Lawrence A Leiter, Carlos Lopez, Patrick J O'Connor, Mary Ellen Sweeney, Daniel Weiss, William T Friedewald, John B Buse, Hertzel C Gerstein, Jeffrey Probstfield, Richard Grimm, Faramarz Ismail-Beigi, David C Goff, Jerome L Fleg, Yves Rosenberg, Robert P Byington
Importance: Patients with type 2 diabetes are at high risk of cardiovascular disease (CVD) in part owing to hypertriglyceridemia and low high-density lipoprotein cholesterol. It is unknown whether adding triglyceride-lowering treatment to statin reduces this risk. Objective: To determine whether fenofibrate reduces CVD risk in statin-treated patients with type 2 diabetes. Design, Setting, and Participants: Extended posttrial follow-up of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid Study participants between July 2009 and October 2014...
December 28, 2016: JAMA Cardiology
https://www.readbyqxmd.com/read/28003852/shugan-xiaozhi-decoction-attenuates-nonalcoholic-steatohepatitis-by-enhancing-ppar%C3%AE-and-l-fabp-expressions-in-high-fat-fed-rats
#9
Yu-Feng Xing, Zhen Zhang, Wen-Jun Fu, Da-Qiao Zhou, Ailsa Chui-Ying Yuen, Daniel Kam-Wah Mok, Chi-On Chan, Guang-Dong Tong
This study aimed to investigate the effects of Shugan Xiaozhi decoction (SX) on nonalcoholic steatohepatitis (NASH) induced by high-fat diet in rats. The rats were randomly divided into 6 groups, namely, control, model, fenofibrate, and three different dosage of SX (10, 20, and 40 g/kg/day, p.o.). After establishing the NASH model, at 8 weeks of the experiment, treatments were administrated intragastrically to the fenofibrate and SX groups. All rats were killed after 4 weeks of treatment. Compared with the model group, alanine aminotransferase (ALT), aspartate aminotransferase (AST), free fatty acid (FFA), total cholesterol (TC), triacylglycerol (TG), and low-density lipoprotein cholesterol (LDL) serum in the serum were significantly reduced in all SX treatment groups in a dose-dependent manner...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28002666/transient-supersaturation-supports-drug-absorption-from-lipid-based-formulations-for-short-periods-of-time-but-ongoing-solubilisation-is-required-for-longer-absorption-periods
#10
Matthew F Crum, Natalie L Trevaskis, Colin W Pouton, Christopher J H Porter
The current studies sought to explore the impact of drug supersaturation and precipitation during the dispersion and digestion of lipid-based formulations (LBF), on in vivo absorption using a coupled in vitro digestion - in vivo perfusion absorption model. Fenofibrate absorption was evaluated from a number of LBFs with different solubilisation and supersaturation capacities, and conditions at the absorptive membrane manipulated by changing perfusion conditions, intestine segment lengths and by the conduct of experiments in the presence or absence of suspended/precipitated drug...
December 21, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27996196/reverse-translational-study-of-fenofibrate-s-observed-effects-in-diabetes-associated-retinopathy
#11
R A Farris, E T Price
Clinical trials suggest that fenofibrate reduces the progression of retinopathies in patients with type 2 diabetes. Furthermore, patients with retinopathies have elevated levels of inflammatory chemokines and dysfunctional retinal angiogenesis. Therefore, we investigated the effects of fenofibrate on the production of inflammatory chemokines and genes associated with angiogenesis. Retinal pigment epithelial cells (RPECs) were cultured with IL-1β and fenofibrate ranging from 1-50 μM. ENA-78, IL-8, and RANTES were measured in cell culture by ELISA...
December 20, 2016: Clinical and Translational Science
https://www.readbyqxmd.com/read/27992863/effects-of-high-density-lipoprotein-raising-therapies-on-cardiovascular-outcomes-in-patients-with-type-2-diabetes-mellitus-with-or-without-renal-impairment-the-action-to-control-cardiovascular-risk-in-diabetes-study
#12
Vasilios Papademetriou, Laura Lovato, Costas Tsioufis, William Cushman, William B Applegate, Amy Mottle, Zubin Punthakee, Eric Nylen, Michael Doumas
BACKGROUND: The role of high density lipoprotein-raising interventions in addition to statin therapy in patients with diabetes remains controversial. Chronic kidney disease (CKD) is a strong modifier of cardiovascular (CV) outcomes. We therefore investigated the impact of CKD status at baseline on outcomes in patients with diabetes randomized to standard statin or statin plus fenofibrate treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial. METHODS: Among 5,464 participants in the ACCORD lipid trial, 3,554 (65%) were free of CKD at baseline, while 1,910 (35%) had mild to moderate CKD...
December 17, 2016: American Journal of Nephrology
https://www.readbyqxmd.com/read/27979751/parp1-mediated-ppar%C3%AE-poly-adp-ribosyl-ation-suppresses-fatty-acid-oxidation-in-non-alcoholic-fatty-liver-disease
#13
Kun Huang, Meng Du, Xin Tan, Ling Yang, Xiangrao Li, Yuhan Jiang, Cheng Wang, Fengxiao Zhang, Feng Zhu, Min Cheng, Qinglin Yang, Liqing Yu, Lin Wang, Dan Huang, Kai Huang
BACKGROUND & AIMS: PARP1 is a key mediator of cellular stress responses and critically in multiple physiological and pathophysiological processes of cells.However, whether it is involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) remains elusive. METHODS: We detect PARP1 activity in liver of mice on high fat diet (HFD), and sample from NAFLD patients. Gain- or loss-of-function approaches are used to investigate the roles and mechanisms of hepatic PARP1 in the pathogenesis of NAFLD...
December 12, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/27973425/zerumbone-a-bioactive-sesquiterpene-ameliorates-diabetes-induced-retinal-microvascular-damage-through-inhibition-of-phospho-p38-mitogen-activated-protein-kinase-and-nuclear-factor-%C3%AE%C2%BAb-pathways
#14
Wayne Young Liu, Thing-Fong Tzeng, I-Min Liu
Zerumbone ameliorates retinal damage by blocking advanced glycation end products and their receptor system in streptozotocin-diabetic rats. Because of the multiple factors involved in diabetic retinopathy (DR) etiology, the mechanisms of zerumbone that are mainly responsible for its ameliorative effect on DR need to be further clarified. In the present study, zerumbone (20 mg or 40 mg/kg) or fenofibric acid (100 mg/kg) was orally administered to diabetic rats by intragastric gavage once daily for three consecutive months...
December 11, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27957241/recent-advances-in-the-diagnosis-and-treatment-of-primary-biliary-cholangitis
#15
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/27940083/statistical-investigation-of-simulated-fed-intestinal-media-composition-on-the-equilibrium-solubility-of-oral-drugs
#16
Zhou Zhou, Claire Dunn, Ibrahim Khadra, Clive G Wilson, Gavin W Halbert
Gastrointestinal fluid is a complex milieu and it is recognised that gut drug solubility is different to that observed in simple aqueous buffers. Simulated gastrointestinal media have been developed covering fasted and fed states to facilitate in vitro prediction of gut solubility and product dissolution. However, the combination of bile salts, phospholipids, fatty acids and proteins in an aqueous buffered system creates multiple phases and drug solubility is therefore a complex interaction between these components, which may create unique environments for each API...
December 7, 2016: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27930988/potential-involvement-of-ppar-%C3%AE-activation-in-diminishing-the-hepatoprotective-effect-of-fenofibrate-in-nafld-accuracy-of-non-invasive-panel-in-determining-the-stage-of-liver-fibrosis-in-rats
#17
Asmaa M Hamed, Omnyah A El-Kharashi, Suzi S A Boctor, Lobna F Abd-Elaziz
BACKGROUND: Although Fenofibrate (FF) is a hypolipedmic drug and one of the PPARα agonists which is a drug target for non alcoholic liver disease (NAFLD), no studies had investigated its potential hepatic effects in such cases. AIM: To compare between the effect of FF and Gemfibrozil (GF) on the prognosis of NAFLD in rats. METHODS: Sixty four rats were used and classified into two main groups. Group I (treated for 6 weeks): naïve, FF, GF groups and Group II (treated for 14 weeks and drugs were added at the last 6 weeks): Control, high fat diet (HFD) untreated, HFD+FF, HFD+FF+folic acid (FA) and HFD+GF groups...
January 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27918198/ppar%C3%AE-dependent-increase-of-mouse-urine-output-by-gemfibrozil-and-fenofibrate
#18
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/27916218/fenofibrate-attenuates-malignant-hypertension-by-suppression-of-the-renin-angiotensin-system-a-study-in-cyp1a1-ren-2-transgenic-rats
#19
Šárka Jíchová, Šárka Doleželová, Libor Kopkan, Elzbieta Kompanowska-Jezierska, Janusz Sadowski, Luděk Červenka
BACKGROUND: Malignant hypertension is a life-threatening condition, and its pathophysiology is still poorly understood. The present study was designed to evaluate the role of interaction of the renin-angiotensin system with 20-hydroxyeicosatetraenoic acid (20-HETE), a product of cytochrome P450 (CYP)-dependent ω-hydroxylase pathway, in the pathophysiology of angiotensin II (ANG II)-dependent malignant hypertension in Cyp1a1-Ren-2 transgenic rats. METHODS: Malignant hypertension was induced by 12 days׳ dietary administration of 0...
December 2016: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/27889747/alisol-a-24-acetate-prevents-hepatic-steatosis-and-metabolic-disorders-in-hepg2-cells
#20
Lu Zeng, WaiJiao Tang, JinJin Yin, LiJuan Feng, Yabing Li, Xiaorui Yao, BenJie Zhou
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic disorders including hepatic lipid accumulation and inflammation. Alisol A 24-acetate, a triterpene from Alismatis rhizome, has multiple biologic activities such as hypolipidemic, anti-inflammatory and anti-diabetic. Thus we hypothesized that Alisol A 24 -acetate would have effect on NAFLD. The present study was conducted to investigate the therapeutic effects and potential mechanisms of Alisol A 24-acetate against hepatic steatosis in a free fatty acids (FFAs) induced NAFLD cell model...
2016: Cellular Physiology and Biochemistry
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