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Hillary T Graham, Daniel M Rotroff, Skylar W Marvel, John B Buse, Tammy M Havener, Alyson G Wilson, Michael J Wagner, Alison A Motsinger-Reif
Given the high costs of conducting a drug-response trial, researchers are now aiming to use retrospective analyses to conduct genome-wide association studies (GWAS) to identify underlying genetic contributions to drug-response variation. To prevent confounding results from a GWAS to investigate drug response, it is necessary to account for concomitant medications, defined as any medication taken concurrently with the primary medication being investigated. We use data from the Action to Control Cardiovascular Disease (ACCORD) trial in order to implement a novel scoring procedure for incorporating concomitant medication information into a linear regression model in preparation for GWAS...
2016: Frontiers in Genetics
Shu Nu Chang-Lee, Hsi-Hsien Hsu, Marthandam Asokan Shibu, Tsung-Jung Ho, Chih-Hao Tsai, Ming-Cheng Chen, Chuan-Chou Tu, Vijaya Padma Viswanadha, Wei- Wen Kuo, Chih-Yang Huang
Peroxisome proliferator-activated receptor-α (PPARα) is a member of the nuclear receptor superfamily involved in hepatocarcinogenesis in rodents. In previous studies on liver tumor tissues, PPARα mRNA expression was found to be significantly higher and overexpression of ERα inhibited the PPARα expression, cell-proliferation and also induced apoptosis in Hep3B cell. However, the role of ERβ is not known yet. Therefore, the aim of this study is to define the role of ERβ on PPARα in Hep3B cells. The effect of PPARα signaling cascade were monitored by inducing Hep3B cells by fenofibrate...
October 18, 2016: Pathology Oncology Research: POR
Grzegorz Szklarz, Karolina Adrjanowicz, Mateusz Dulski, Justyna Knapik, Marian Paluch
In this work, we have carefully investigated the molecular dynamics in the supercooled liquid and glassy states of the pharmaceutical agent fenofibrate. To do that dielectric relaxation studies at ambient and the elevated pressure were performed. Data collected at atmospheric pressure were found to be in a good agreement with that already reported in the literature. High-pressure studies enable us to distinguish the secondary relaxation processes of the different molecular origin. This includes (i) pressure insensitive $\gamma$-relaxation of the activation energy $E_a$=28 kJ/mol and (ii) $\beta$-relaxation that senses the density increase and originates most probably from the intermolecular movements ($E_a$=77 kJ/mol at 480 MPa)...
October 17, 2016: Journal of Physical Chemistry. B
Amirhossein Sahebkar, Matteo Pirro, Željko Reiner, Arrigo Cicero, Gianna Ferretti, Mario Simental-Mendía, Luis E Simental-Mendía
BACKGROUND: Plasma homocysteine is an independent non-traditional risk factor for atherosclerotic cardiovascular disease. The impact of statin therapy on plasma homocysteine is not conclusive. OBJECTIVE: To evaluate the effect of statin therapy on plasma homocysteine concentrations in a systematic review and meta-analysis of controlled clinical trials. The secondary aim was to assess the comparative effect of statins versus fibrates on plasma homocysteine levels in head-to-head trials...
October 7, 2016: Current Medicinal Chemistry
Stephanie Cham, Hayley J Koslik, Beatrice A Golomb
Psychiatric adverse drug reactions (ADRs) have been reported with statin use, but the literature regarding statin-associated mood/behavioral changes remains limited. We sought to elicit information germane to natural history and characteristics of central nervous system/behavioral changes in apparent connection with statin and/or cholesterol-lowering drug use, and delineate mechanisms that may bear on an association. Participants (and/or proxies) self-referred with behavioral and/or mood changes in apparent association with statins completed a survey eliciting cholesterol-lowering drug history, character and impact of behavioral/mood effect, time-course of onset and recovery in relation to drug use/modification, co-occurrence of recognized statin-associated ADRs, and factors relevant to ADR causality determination...
December 2016: Drug Saf Case Rep
Yan Wang, Min Yu, Yue Ma, Ruo Ping Wang, Wei Liu, Wei Xia, Ai Li Guan, Cong Hui Xing, Fei Lu, Xiao Ping Ji
Peroxisome proliferator-activated receptors alpha (PPARα) is a therapy target in atherosclerosis and cardiovascular diseases. However, anti-inflammatory effects of PPARα in intracerebral hemorrhage (ICH) remain unknown. We investigated the anti-inflammatory effects of fenofibrate, a ligand of PPARα, in ICH rat model. We found that engagement of fenofibrate increased nissl body and astrocytes, and reduced the neuronal damage, which was observed in paraffin section of ICH rat brain. Fenofibrate also promoted the proliferation of astrocytes that were isolated from adult rat brain...
October 14, 2016: Current Neurovascular Research
Xinchi Wu, Juan Xu
Hispidulin is a naturally occurring flavonoid isolated from a traditional Chinese medicinal herb, Saussurea involucrata. In this study, the regulating role of hispidulin on the mRNA expression level of enzymes involved in lipid metabolism was examined in vitro and in vivo. Moreover, the in vivo lipid-modulating effect of hispidulin was compared with that of fenofibrate, a classical PPARα agonist. Our results in present study demonstrated that hispidulin can directly bind to and activate PPARα as an agonist and thus modulate the downstream lipid-metabolizing genes...
October 15, 2016: Lipids
Hyo Min Park, Kim A Russo, Grigory Karateev, Michael Park, Elena Dubikovskaya, Lance J Kriegsfeld, Andreas Stahl
Alterations in hepatic free fatty acid (FFA) uptake and metabolism contribute to development of prevalent liver disorders such as hepatosteatosis. However, detecting dynamic changes in FFA uptake by the liver in live model organisms has proven difficult. To enable non-invasive real-time imaging of FFA flux in the liver, we generated transgenic mice with liver-specific expression of luciferase and performed bioluminescence imaging with an FFA probe. Our approach enabled us to observe the changes in FFA hepatic uptake under different physiological conditions in live animals...
October 11, 2016: Gastroenterology
B S Bal, Ashok Duggal, Mandeep Kaur, Sarabjit Singh, Tajinder Kaur
No abstract text is available yet for this article.
January 2016: Journal of the Association of Physicians of India
Yan Gong, Zhuo Shao, Zhongjie Fu, Matthew L Edin, Ye Sun, Raffael G Liegl, Zhongxiao Wang, Chi-Hsiu Liu, Samuel B Burnim, Steven S Meng, Fred B Lih, John Paul SanGiovanni, Darryl C Zeldin, Ann Hellström, Lois E H Smith
Neovascular eye diseases including retinopathy of prematurity, diabetic retinopathy and age-related-macular-degeneration are major causes of blindness. Fenofibrate treatment in type 2 diabetes patients reduces progression of diabetic retinopathy independent of its peroxisome proliferator-activated receptor (PPAR)α agonist lipid lowering effect. The mechanism is unknown. Fenofibrate binds to and inhibits cytochrome P450 epoxygenase (CYP)2C with higher affinity than to PPARα. CYP2C metabolizes ω-3 long-chain polyunsaturated fatty acids (LCPUFAs)...
September 30, 2016: EBioMedicine
Ashok Mandala, Nabanita Das, Sudarshan Bhattacharjee, Bidisha Mukherjee, Satinath Mukhopadhyay, Sib Sankar Roy
Insulin resistance (IR) is an important determinant of type-2 diabetes mellitus (T2DM). Free fatty acids (FFAs) induce IR by various mechanisms. A surfeit of circulating FFA leads to intra-myocellular lipid accumulation that induces mitochondrial ROS generation and worsens IR. However, the molecular mechanisms behind are unclear. We identified thioredoxin interacting protein (TxNIP), which is overexpressed in T2DM, to be a promoter of ROS-induced IR. We observed upregulation of TxNIP upon palmitate treatment in skeletal muscle cells that led to ROS generation and Glut-4 downregulation resulting in impaired glucose-uptake...
October 28, 2016: Biochemical and Biophysical Research Communications
Hala El Rami, Rasha Barham, Jennifer K Sun, Paolo S Silva
Diabetic retinopathy (DR) is the most frequent microvascular complication from diabetes and requires annual screening and at least annual follow-up. A systemic approach to optimize blood glucose and blood pressure may halt progression to severe stages of DR and obviate the need for ocular treatment. Although there is evidence of benefit from fenofibrate or intravitreous antiVEGF treatment for eyes with nonproliferative DR (NPDR), these therapies are not standard care for NPDR at this time. Some patients with severe NPDR, especially those with type 2 diabetes, benefit from early panretinal photocoagulation (PRP)...
October 4, 2016: Seminars in Ophthalmology
Meetali Deori, Dipali Devi, Sima Kumari, Ankita Hazarika, Himadri Kalita, Rahul Sarma, Rajlakshmi Devi
This study evaluated the antioxidant effect of crude sericin extract (CSE) from Antheraea assamensis in high cholesterol fed rats. Investigation was conducted by administering graded oral dose of 0.25 and 0.5 gm/kg body weight (b.w.)/day of CSE for a period of 28 days. Experiments were conducted in 30 rats and were divided into five groups: normal control, high cholesterol fed (HCF), HCF + 0.065 gm/kg b.w./day fenofibrate (FF), HCF + sericin 0.25 gm/kg b.w./day (LSD), and HCF + sericin 0.5 gm/kg b.w./day (HSD)...
2016: Frontiers in Pharmacology
Mutsuko Hirata-Koizumi, Ryota Ise, Hirohito Kato, Takashi Matsuyama, Tomoko Nishimaki-Mogami, Mika Takahashi, Atsushi Ono, Makoto Ema, Akihiko Hirose
2-(2'-Hydroxy-3',5'-di-tert-butylphenyl)benzotriazole (HDBB), the Benzotriazole UV-stabilizer (BUVSs) known as UV-320, is widely used in plastic materials for protection against UV-irradiation. Previously, we reported that oral ingestion of HDBB induce hepatotoxicity including hepatocyte hypertrophy and necrosis in rats and, males was more susceptible compared with females in young rats while no sex-related difference was observed in preweaning rats. Phenotypes observed in our previous study imply involvement of peroxisome proliferator-activated receptor (PPAR) α in HDBB hepatotoxicity, however, direct evidence that HDBB can activate PPARα has not been provided and the mechanism which underlying the gender difference of HDBB hepatotoxicity was not clearly elucidated...
2016: Journal of Toxicological Sciences
Sadeesh K Ramakrishnan, Lucia Russo, Simona S Ghanem, Payal R Patel, Ana Maria Oyarce, Garrett Heinrich, Sonia M Najjar
High-fat diet reduces the expression of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a transmembrane glycoprotein that promotes insulin clearance and downregulates fatty acid synthase activity in the liver upon its phosphorylation by the insulin receptor. Because peroxisome proliferator-activated receptoralpha (PPARalpha) transcriptionally suppresses CEACAM1 expression, we herein examined whether high-fat downregulates CEACAM1 expression in a PPARalpha;-dependent mechanism. By activating PPARalpha, the lipid-lowering drug fenofibrate reverses dyslipidemia and improves insulin sensitivity in type 2 diabetes in part by promoting fatty acid oxidation...
September 23, 2016: Journal of Biological Chemistry
I Sukhotnik, N Nissimov, Y Ben Shahar, D Moati, N Bitterman, Y Pollak, D Berkowitz, A G Coran, A Bitterman
PURPOSE: Fenofibrate (FEN) is known as a nuclear receptor activator which regulates many pathophysiological processes, such as oxidative stress, inflammation, and leukocyte endothelium interactions. Recent studies have demonstrated an anti-oxidant, anti-inflammatory, and anti-ischemic role of FEN in the attenuation of ischemia-reperfusion (IR) injury in the kidney, liver, brain, and heart. The purpose of the present study was to examine the effect of FEN on intestinal recovery and enterocyte turnover after intestinal IR injury in rats...
September 20, 2016: Pediatric Surgery International
Katarina Bukara, Laurent Schueller, Jan Rosier, Mark A Martens, Tinne Daems, Loes Verheyden, Siemon Eelen, Michiel Van Speybroeck, Cristian Libanati, Johan A Martens, Guy Van Den Mooter, Françoise Frérart, Koen Jolling, Marjan De Gieter, Branko Bugarski, Filip Kiekens
Formulating poorly water soluble drugs using ordered mesoporous silica materials is an emerging approach to tackle solubility-related bioavailability problems. The current study was conducted to assess the bioavailability-enhancing potential of ordered mesoporous silica in man. In this open-label, randomized, two-way cross-over study, 12 overnight fasted healthy volunteers received a single dose of fenofibrate formulated with ordered mesoporous silica or a marketed product based on micronized fenofibrate. Plasma concentrations of fenofibric acid, the pharmacologically active metabolite of fenofibrate, were monitored up to 96h post-dose...
September 17, 2016: European Journal of Pharmaceutics and Biopharmaceutics
Mohammad Azad, Jacqueline Moreno, Ecevit Bilgili, Rajesh Davé
Formation of core-shell nanocomposites of Fenofibrate and Itraconazole, model poorly water soluble drugs, via fluidized bed (FB) coating of their well-stabilized high drug loaded nanosuspensions is investigated. Specifically, the extent of dissolution enhancement, when fine carrier particles (sub-50μm) as opposed to the traditional large carrier particles (>300μm) are used, is examined. This allows testing the hypothesis that greatly increased carrier surface area and more importantly, thinner shell for finer carriers at the same drug loading can significantly increase the dissolution rate when spray-coated nanosuspensions are well-stabilized...
September 14, 2016: International Journal of Pharmaceutics
Hsu-Lung Jen, Wei-Hsian Yin, Jaw-Wen Chen, Shing-Jong Lin
AIM: Previous studies demonstrated that endothelin-1 (ET-1) can significantly increase the cell size and stimulate adiponectin expression in cultured human cardiomyocytes (HCM). The aim of the present study was to investigate the effects of fenofibrate, a peroxisome proliferator-activated receptor-α (PPARα) activator, on cell hypertrophy and adiponectin expression in vitro and in a rat model of daunorubicin-induced cardiomyopathy. METHODS: The cultured human cardiomyocytes (HCM) were stimulated with or without ET-1...
September 15, 2016: Journal of Atherosclerosis and Thrombosis
Michal Vrablík
UNLABELLED: Dyslipidemia in type 2 diabetics represents a complex change of lipoprotein metabolism that is highly proatherogenic. It originates on a genetic background in the context of insulin resistance and affects lipoprotein metabolism at multiple levels (e.g. hepatocyte, enterocyte, intravascular processing) mainly in the postprandial phase. The treatment of diabetic (atherogenic) dyslipidemia is an effective option to lower the risk of both macro- and microvascular complications of diabetes...
2016: Vnitr̆ní Lékar̆ství
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