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Fenofibrate

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https://www.readbyqxmd.com/read/28817808/ppar%C3%AE-agonist-stimulated-angiogenesis-by-improving-endothelial-precursor-cell-function-via-a-nlrp3-inflammasome-pathway
#1
Yaping Deng, Xue Han, Zheng Yao, Yuannan Sun, Jiawen Yu, Jian Cai, Guofei Ren, Guojun Jiang, Feng Han
BACKGROUND: Impaired wound healing is a common complication of diabetes and is the leading cause of lower extremity amputation. Treatment with fenofibrate, a peroxisome proliferators-activated receptor α (PPARα) agonist, was associated with a lower risk of amputations, particularly minor amputations without known large-vessel diseases, probably through non-lipid mechanisms. The current study aimed to test our hypothesis that fenofibrate stimulates angiogenesis and restores endothelial precursor cell (EPC) function via inhibiting Nod-like receptor protein 3 (NLRP3) inflammasome in streptozotocin (STZ)-induced diabetic mice...
August 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28807819/carrier-characteristics-influence-the-kinetics-of-passive-drug-loading-into-lipid-nanoemulsions
#2
Katrin Göke, Heike Bunjes
Passive loading as a novel screening approach is a material-saving tool for the efficient selection of a suitable colloidal lipid carrier system for poorly water soluble drug candidates. This method comprises incubation of preformed carrier systems with drug powder and subsequent determination of the resulting drug load of the carrier particles after removal of excess drug. For reliable routine use and to obtain meaningful loading results, information on the kinetics of the process is required. Passive loading proceeds via a dissolution-diffusion based mechanism, where drug surface area and drug water solubility are key parameters for fast passive loading...
August 11, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28769774/fenofibrate-administration-reduces-alcohol-and-saccharin-intake-in-rats-possible-effects-at-peripheral-and-central-levels
#3
Mario Rivera-Meza, Daniel Muñoz, Erik Jerez, María E Quintanilla, Catalina Salinas-Luypaert, Katia Fernandez, Eduardo Karahanian
We have previously shown that the administration of fenofibrate to high-drinker UChB rats markedly reduces voluntary ethanol intake. Fenofibrate is a peroxisome proliferator-activated receptor alpha (PPARα) agonist, which induces the proliferation of peroxisomes in the liver, leading to increases in catalase levels that result in acetaldehyde accumulation at aversive levels in the blood when animals consume ethanol. In these new studies, we aimed to investigate if the effect of fenofibrate on ethanol intake is produced exclusively in the liver (increasing catalase and systemic levels of acetaldehyde) or there might be additional effects at central level...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28767589/effects-of-fenofibrate-on-inflammatory-cytokines-in-diabetic-retinopathy-patients
#4
Hai-Bing Ju, Fu-Xian Zhang, Shuang Wang, Jie Song, Tao Cui, Li-Feng Li, Hai-Yan Zhang
The role of cytokines in diabetic retinopathy (DR) and effects of fenofibrate on cytokines were explored by observing changes in serum IL-1β, TNF-α, VEGF, and Lp-PLA2 in different stages of DR and the intervention effect of oral fenofibrate on cytokines.In total, 190 patients with type 2 DR were enrolled and divided into 3 groups: diabetic without retinopathy (NDR) group (n = 30), nonproliferative diabetic retinopathy (NPDR) group (n = 80), and proliferative diabetic retinopathy (PDR) group (n = 80)...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28766701/rationale-for-an-adjunctive-therapy-with-fenofibrate-in-pharmacoresistant-nocturnal-frontal-lobe-epilepsy
#5
Monica Puligheddu, Miriam Melis, Giuliano Pillolla, Giulia Milioli, Liborio Parrino, Giovanni Mario Terzano, Sonia Aroni, Claudia Sagheddu, Francesco Marrosu, Marco Pistis, Anna Lisa Muntoni
OBJECTIVE: Nocturnal frontal lobe epilepsy (NFLE) is an idiopathic partial epilepsy with a family history in about 25% of cases, with autosomal dominant inheritance (autosomal dominant NFLE [ADNFLE]). Traditional antiepileptic drugs are effective in about 55% of patients, whereas the rest remains refractory. One of the key pathogenetic mechanisms is a gain of function of neuronal nicotinic acetylcholine receptors (nAChRs) containing the mutated α4 or β2 subunits. Fenofibrate, a common lipid-regulating drug, is an agonist at peroxisome proliferator-activated receptor alpha (PPARα) that is a ligand-activated transcription factor, which negatively modulates the function of β2-containing nAChR...
August 2, 2017: Epilepsia
https://www.readbyqxmd.com/read/28752027/the-potential-of-natural-products-for-targeting-ppar%C3%AE
#6
REVIEW
Daniela Rigano, Carmina Sirignano, Orazio Taglialatela-Scafati
Peroxisome proliferator activated receptors (PPARs) α, -γ and -β/δ are ligand-activated transcription factors and members of the superfamily of nuclear hormone receptor. These receptors play key roles in maintaining glucose and lipid homeostasis by modulating gene expression. PPARs constitute a recognized druggable target and indeed several classes of drugs used in the treatment of metabolic disease symptoms, such as dyslipidemia (fibrates, e.g. fenofibrate and gemfibrozil) and diabetes (thiazolidinediones, e...
July 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28749696/the-influence-of-physiological-gastrointestinal-surfactant-ratio-on-the-equilibrium-solubility-of-bcs-class-ii-drugs-investigated-using-a-four-component-mixture-design
#7
Zhou Zhou, Claire Dunn, Ibrahim Khadra, Clive G Wilson, Gavin W Halbert
The absorption of poorly water-soluble drugs is influenced by the luminal gastrointestinal fluid content and composition which controls solubility. Simulated intestinal fluids have been introduced into dissolution testing including endogenous amphiphiles and digested lipids at physiological levels; however, in vivo individual variation exists in the concentrations of these components, which will alter drug absorption through an effect on solubility. The use of a factorial design of experiment and varying media by introducing different levels of bile, lecithin and digested lipids has been previously reported, but here we investigate the solubility variation of poorly-soluble drugs through more complex biorelevant amphiphile interactions...
July 27, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28741179/activation-of-liver-x-receptor-inhibits-oct2-mediated-organic-cation-transport-in-renal-proximal-tubular-cells
#8
Teerasak Wongwan, Suticha Kittayaruksakul, Nithi Asavapanumas, Varanuj Chatsudthipong, Sunhapas Soodvilai
Liver X receptor (LXR) is transcriptional factor that plays an important role in the regulation of energy metabolism such as cholesterol, lipid, and glucose metabolism as well as membrane transporters and channels. Using both in vitro and in vivo models, LXR regulation of the expression and function of renal organic cation transporter 2 (OCT2) was observed. Synthetic LXR agonist (GW3965) and endogenous LXR agonist (22R-hydroxycholesterol) significantly reduced the uptake of (3)H-MPP(+), a prototypic substrate of OCT2, in both OCT2- Chinese hamster ovary K1 and human renal proximal tubular cells (RPTEC/TERT1)...
July 25, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28736931/genetic-variants-in-hsd17b3-smad3-and-ipo11-impact-circulating-lipids-in-response-to-fenofibrate-in-individuals-with-type-2-diabetes
#9
Daniel M Rotroff, Sonja S Pijut, Skylar W Marvel, John R Jack, Tammy M Havener, Aurora Pujol, Agatha Schluter, Greg A Graf, Henry N Ginsberg, Hetal S Shah, He Gao, Mario-Luca Morieri, Alessandro Doria, Josyf C Mychaleckyi, Howard L McLeod, John B Buse, Michael J Wagner, Alison A Motsinger-Reif
Individuals with type 2 diabetes (T2D) and dyslipidemia are at an increased risk of cardiovascular disease. Fibrates are a class of drugs prescribed to treat dyslipidemia, but variation in response has been observed. To evaluate common and rare genetic variants that impact lipid responses to fenofibrate in statin-treated T2D patients, we examined lipid changes in response to fenofibrate therapy using genome-wide association(GWA). Associations were followed-up using gene expression studies in mice. Common variants in SMAD3 and IPO11 were marginally associated with lipid changes in black subjects(p<5x10(-6) )...
July 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28733879/anticancer-activity-of-salicin-and-fenofibrate
#10
Marwa Sabaa, Hassan M ELFayoumi, Shimaa Elshazly, Mahmoud Youns, Waleed Barakat
Cancer refers to a disorder of cell proliferation that leads to tumor production. Cancer is usually treated by surgery, chemotherapeutic drugs, and radiation. Despite the presence of many anticancer drugs, cancer is still an uncontrolled disease and is a major cause of death worldwide. In addition, most anticancer drugs have severe side effects that can limit their use in some patients. This study aims to investigate the possible anticancer activity of two clinically used drugs: a natural antioxidant agent (salicin) and an antihyperlipidemic agent (fenofibrate) against two breast cancer models (in vivo EAC and in vitro MCF7) and the pancreatic cancer cell line (Panc-1)...
July 21, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28733242/dual-centrifugation-a-new-technique-for-nanomilling-of-poorly-soluble-drugs-and-formulation-screening-by-an-doe-approach
#11
Martin Hagedorn, Ansgar Bögershausen, Matthias Rischer, Rolf Schubert, Ulrich Massing
The development of nanosuspensions of poorly soluble APIs takes a lot of time and high amount of active material is needed. In this publication the use of dual centrifugation (DC) for an effective and rapid API-nanomilling is described for the first time. DC differs from normal centrifugation by an additional rotation of the samples during centrifugation, resulting in a very fast and powerful movement of the samples inside the vials, which - in combination with milling beads - result in effective milling. DC-nanomilling was compared to conventional wet ball milling and results in same or even smaller particle sizes...
July 18, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28730672/lipid-lowering-therapy-of-everolimus-related-severe-hypertriglyceridaemia-in-a-pancreatic-neuroendocrine-tumour-pnet
#12
V De Gennaro Colonna, C Pavanello, F Rusconi, A Sartore-Bianchi, S Siena, S Castelnuovo, C R Sirtori, G Mombelli
WHAT IS KNOWN AND OBJECTIVE: Hypertriglyceridaemia (HTG) is a potentially serious side effect of everolimus therapy. We here report a case of severe HTG in an everolimus-treated patient and provide recommendations for its management. CASE SUMMARY: The patient was a 70-year-old woman, being treated with everolimus for a pancreatic neuroendocrine tumour (pNET). She developed severe HTG to a maximum of 969 mg/dL after 22 months of therapy. Treatment with fenofibrate rapidly normalized triglyceride (TG) levels...
July 21, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28725307/acute-pancreatitis-secondary-to-severe-hypertriglyceridemia-management-of-severe-hypertriglyceridemia-in-emergency-setting
#13
Ahmad Chaudhary, Umair Iqbal, Hafsa Anwar, Hafiz Umair Siddiqui, Madiha Alvi
Hypertriglyceridemia (HTG) is the third most common cause of acute pancreatitis (AP). The incidence of AP is around 10-20% with levels > 2,000 mg/dL. We present here a case of a 44-year-old male with history of uncontrolled diabetes mellitus and HTG admitted with severe abdominal pain. Labs revealed elevated lipase and amylase. CT of abdomen with contrast showed AP. He was found to have a triglyceride (TG) level of 6,672 mg/dL. Besides conventional treatment for AP with intravenous (IV) hydration, he was started on IV regular insulin along with dextrose saline...
June 2017: Gastroenterology Research
https://www.readbyqxmd.com/read/28716724/the-ppar%C3%AE-activator-fenofibrate-inhibits-voltage-dependent-k-channels-in-rabbit-coronary-arterial-smooth-muscle-cells
#14
Hongliang Li, Sung Eun Shin, Mi Seon Seo, Jin Ryeol An, Won-Kyo Jung, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Hyoweon Bang, Young Min Bae, Amy L Firth, Il-Whan Choi, Won Sun Park
We examined the effects of the PPARα activator fenofibrate on voltage-dependent K(+) (Kv) channels using a patch clamp technique in native rabbit coronary arterial smooth muscle cells. Kv current was inhibited by application of fenofibrate in a concentration-dependent manner, with an apparent IC50 value of 6.39 ± 0.53μM and a slope value (Hill coefficient) of 1.63 ± 0.10. Fenofibrate accelerated the decay rate of Kv channel inactivation. The rate constants of association and dissociation for fenofibrate were 0...
July 14, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28705617/drug-solubility-in-lipid-nanocarriers-influence-of-lipid-matrix-and-available-interfacial-area
#15
Katrin Göke, Heike Bunjes
Amongst other strategies for the formulation of poorly water-soluble drugs, solubilization of these drugs in lipid-based formulations is a promising option. Most screening methods for the identification of a suitable lipid-based formulation fail to elucidate the role interfacial effects play for drug solubility in disperse systems. In a novel screening approach called passive drug loading, different preformed lipid nanocarrier dispersions are incubated with drug powder. Afterwards, undissolved drug is filtered off and the amount of solubilized drug is determined...
July 10, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28702816/enhancing-the-solubility-of-fenofibrate-by-nanocrystal-formation-and-encapsulation
#16
Raj Kumar, Prem Felix Siril
Development of techniques to enhance bioavailability of drugs having poor water solubility is a big challenge for pharmaceutical industry. Solubility can be enhanced by particle size reduction and encapsulation using hydrophilic polymers. Fenofibrate (FF) is a drug for regulating lipids. Multi-fold enhancement in solubility of FF has been achieved by nanocrystal formation in the present study. Nanoparticles were prepared by an evaporation-assisted solvent-antisolvent interaction (EASAI) approach. Water-soluble polymers, viz...
July 12, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28699773/variability-amongst-urine-toxicology-amphetamine-readings-with-concurrent-administration-of-fenofibrate
#17
Navin Dadlani, Anna Farrar, Graham Jones
OBJECTIVE: The aim of this study was to highlight that concurrent administration of the common lipid-lowering agent fenofibrate may lead to false-positive amphetamine results in often-used immunoassay-based urine drug screens. It also aimed to show that there are significant moral and clinical challenges associated with the interpretation of such results amongst psychiatric inpatients. CONCLUSIONS: It is evident that different pathology laboratories may utilise different commercial urine drug-screen immunoassays in their toxicology analysis, with variability in the test specificities...
July 1, 2017: Australasian Psychiatry: Bulletin of Royal Australian and New Zealand College of Psychiatrists
https://www.readbyqxmd.com/read/28698097/enzymatic-reactive-oxygen-species-assay-to-evaluate-phototoxic-risk-of-metabolites
#18
Masashi Kato, Hiroto Ohtake, Hideyuki Sato, Yoshiki Seto, Satomi Onoue
The present study aimed to verify the feasibility of an enzymatic reactive oxygen species (eROS) assay to evaluate the phototoxic risk of compounds after their metabolization. The eROS assay was designed based on the combined use of an in vitro drug metabolism system and a ROS assay. The incubation time of compounds with human hepatic S9 fractions was optimized with the use of fenofibrate (FF), a typical phototoxicant with metabolite-related phototoxicity, and the reproducibility and robustness of the eROS assay were examined using FF...
July 8, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28673294/lipid-management-in-india-a-nationwide-cross-sectional-physician-survey
#19
Gurpreet S Wander, Uday M Jadhav, Amruta Chemburkar, Meena Lopez, Jaideep Gogtay
BACKGROUND: Current international guidelines on dyslipidemia are not concordant on various aspects of management. Also, there are no uniformly accepted Indian guidelines. We, therefore, performed a physician survey to understand lipid management practices in India. METHODS: An anonymous survey questionnaire was administered to gauge physicians' self-reported behavior regarding lipid management aspects. Results were expressed in terms of percentages based on the number of responses obtained...
July 3, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28668840/in-vitro-apoptosis-induction-by-fenofibrate-in-lymphoma-and-multiple-myeloma
#20
Leonard Christopher Schmeel, Frederic Carsten Schmeel, Ingo G H Schmidt-Wolf
BACKGROUND/AIM: Recent innovations in the treatment of multiple myeloma have enriched our therapeutic repertoire regarding the treatment of multiple myeloma during the last decades. However, despite today's therapies many multiple myeloma (MM) patients experience relapse of disease and eventually remain incurable. Wnt/β-catenin signaling has been demonstrated in lymphoma and MM, rendering related signaling molecules promising therapeutic targets. Fenofibrate, an extensively scrutinized and widely used drug for primary hypercholesterolemia or mixed dyslipidemia, has proven anticarcinogenic properties mediated by peroxisome proliferator-activated receptor-alpha (PPARα) agonism, thereby also influencing WNT-associated signaling molecules...
July 2017: Anticancer Research
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