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https://www.readbyqxmd.com/read/28343425/ppar-%C3%AE-agonists-are-still-on-the-rise-an-update-on-clinical-and-experimental-findings
#1
Nicola Ferri, Alberto Corsini, Cesare Sirtori, Massimiliano Ruscica
Non-fasting plasma triglyceride (TG) and remnant cholesterol levels, cholesterol content of triglyceride-rich lipoproteins, have been suggested to be an additional cause of cardiovascular diseases; thus, pharmacological TG-lowering with fibrates, activators of PPAR-alpha system, has been linked to risk reduction. Areas covered: This manuscript reviews available evidence on clinical trials involving highly selective PPAR-α agonists (i.e., pemafibrate) and drugs used in the pre-clinical and experimental setting (e...
March 27, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28340451/the-role-of-drug-drug-interactions-in-prostate-cancer-treatment-focus-on-abiraterone-acetate-prednisone-and-enzalutamide
#2
REVIEW
Marzia Del Re, Stefano Fogli, Lisa Derosa, Francesco Massari, Paul De Souza, Stefania Crucitta, Sergio Bracarda, Daniele Santini, Romano Danesi
Elderly patients with cancer may have comorbidities, each requiring additional pharmacologic treatment. Therefore, the occurrence of pharmacokinetic (PK) and pharmacodynamic (PD) interactions is very likely, and the risk of adverse reactions (ADRs), due to the narrow therapeutic window of anticancer drugs, is increased. Drug-drug interactions (DDIs) may occur in prostate cancer patients due to inhibition by abiraterone of liver cytochrome P450 (CYP)-dependent enzymes CYP2C8 and 2D6, which are involved in the metabolism of approximately 25% of all drugs, and induction by enzalutamide of CYP3A4, 2C9 and 2C19, which metabolize up to 50% of medications...
March 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28296193/investigating-transporter-mediated-drug-drug-interactions-using-a-physiologically-based-pharmacokinetic-model-of-rosuvastatin
#3
Q Wang, M Zheng, T Leil
Rosuvastatin is a frequently used probe in transporter-mediated drug-drug interaction (DDI) studies. This report describes the development of a physiologically based pharmacokinetic (PBPK) model of rosuvastatin for prediction of pharmacokinetic (PK) DDIs. The rosuvastatin model predicted the observed single (i.v. and oral) and multiple dose PK profiles, as well as the impact of coadministration with transporter inhibitors. The predicted effects of rifampin and cyclosporine (6.58-fold and 5.07-fold increase in rosuvastatin area under the curve (AUC), respectively) were mediated primarily via inhibition of hepatic organic anion-transporting polypeptide (OATP)1B1 (Inhibition constant (Ki ) ∼1...
March 13, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28284639/transport-behavior-of-the-pharmaceutical-compounds-carbamazepine-sulfamethoxazole-gemfibrozil-ibuprofen-and-naproxen-and-the-lifestyle-drug-caffeine-in-saturated-laboratory-columns
#4
Klaus H Hebig, Laura G Groza, Michelle J Sabourin, Traugott J Scheytt, Carol J Ptacek
Despite the large number of pharmaceutically active compounds found in natural environments little is known about their transport behavior in groundwater, which is complicated by their wide range of physical and chemical properties. The transport behavior of five widely used and often detected pharmaceutical compounds and one lifestyle drug has therefore been investigated, using a set of three column experiments. The investigated compounds were the anticonvulsant carbamazepine, the lifestyle drug caffeine, the antibiotic sulfamethoxazole, the lipid regulator gemfibrozil, and the nonsteroidal anti-inflammatories ibuprofen and naproxen...
March 8, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28199788/development-of-fluorescence-surrogates-to-predict-the-photochemical-transformation-of-pharmaceuticals-in-wastewater-effluents
#5
Shuwen Yan, Bo Yao, Lushi Lian, Xinchen Lu, Shane A Snyder, Rui Li, Weihua Song
The photochemical transformation of pharmaceutical and personal care products (PPCPs) in wastewater effluents is an emerging concern for environmental scientists. In the current study, the photodegradation of 29 PPCPs was examined in effluents under simulated solar irradiation. Direct photodegradation, triplet state effluent organic matter ((3)EfOM*)-mediated and hydroxyl radical (HO(•))-mediated degradation are three major pathways in the removal process. With the photodegradation of trace levels of PPCPs, the excitation-emission matrix (EEM) fluorescence intensities of the effluents were also gradually reduced...
February 24, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28199020/gemfibrozil-food-and-drug-administration-approved-lipid-lowering-drug-increases-longevity-in-mouse-model-of-late-infantile-neuronal-ceroid-lipofuscinosis
#6
Arunava Ghosh, Suresh Babu Rangasamy, Khushbu K Modi, Kalipada Pahan
Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL) is a rare neurodegenerative disease caused by mutations in the Cln2 gene that leads to deficiency or loss of function of the tripeptidyl peptidase 1 (TPP1) enzyme. TPP1 deficiency is known to cause the accumulation of autofluoroscent lipid-protein pigments in brain. Similar to other neurodegenerative disorders, LINCL is also associated with neuroinflammation and neuronal damage. Despite investigations, no effective therapy is currently available for LINCL...
February 15, 2017: Journal of Neurochemistry
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
#7
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/28057168/evaluation-and-optimization-of-blood-micro-sampling-methods-serial-sampling-in-a-cross-over-design-from-an-individual-mouse
#8
Nita J Patel, Enaksha Wickremsinhe, Yu-Hua Hui, Alexandar Barr, Nicholas Masterson, Kenneth Ruterbories, Jennifer Weller, Jennifer Hanes, Tom Kern, Everett Perkins
PURPOSE: Current practices applied to mouse pharmacokinetic (PK) studies often use large numbers of animals with sporadic or composite sampling that inadequately describe PK profiles.  The purpose of this work was to evaluate and optimize blood microsampling techniques coupled with dried blood spot (DBS) and LC-MS/MS analysis to generate reliable PK data in mice.  In addition, the feasibility of cross-over designs was assessed and recommendations are presented. METHODS: The work describes a comprehensive evaluation of five blood microsampling techniques (tail clip, tail vein with needle hub, submandibular, retro-orbital, and saphenous bleeding) in CD-1 mice...
October 2016: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27987461/modelling-the-photochemical-attenuation-pathways-of-the-fibrate-drug-gemfibrozil-in-surface-waters
#9
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/27958766/association-of-serum-triglyceride-level-and-gemfibrozil-consumption-with-periodontal-status
#10
Ferena Sayar, Nasrin Akhondi, Soltanali Fallah, Amir Abbas Moalemnia, Azra Cheraghi
BACKGROUND: Hyperlipidemia is a major risk factor for cardiovascular diseases. Considering the suggested association between periodontal and cardiovascular diseases, this study sought to assess the association, if any, between serum triglyceride (TG) levels and gemfibrozil consumption with periodontal parameters. METHODS: This cross-sectional study was conducted on 90 participants including 30 individuals with a normal lipid profile (group H), 30 hypertriglyceridemic patients not on medication (group N) and 30 hypertriglyceridemic patients taking gemfibrozil over a three month period (group M)...
December 13, 2016: Journal of Periodontology
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
#11
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
#12
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/27915128/cholesterol-reducing-agents-inhibit-assembly-of-type-i-parainfluenza-viruses
#13
Shringkhala Bajimaya, Tsuyoshi Hayashi, Tünde Frankl, Peter Bryk, Brian Ward, Toru Takimoto
Many enveloped RNA viruses utilize lipid rafts for the assembly of progeny virions, but the role of cholesterol, a major component of rafts, on paramyxovirus budding and virion formation is controversial. In this study, we analyzed the effects of FDA-approved cholesterol-reducing agents, gemfibrozil and lovastatin, on raft formation and assembly of human parainfluenza virus type 1 (hPIV1) and Sendai virus (SeV). Treatment of the human airway epithelial A549 cells with the agents, especially when combined, significantly decreased production of infectious hPIV1 and SeV...
January 15, 2017: Virology
https://www.readbyqxmd.com/read/27909849/monitoring-contaminants-of-emerging-concern-from-tertiary-wastewater-treatment-plants-using-passive-sampling-modelled-with-performance-reference-compounds
#14
Tamanna Sultana, Craig Murray, M Ehsanul Hoque, Chris D Metcalfe
The Lake Simcoe watershed in Ontario, Canada is an important recreational area and a recharge zone for groundwater resources. Lake Simcoe is a relatively shallow lotic system that has been impacted by urban development, recreation, industry and agriculture. As part of a watershed management plan, six wastewater treatment plants (WWTPs) located in this catchment basin were selected to measure the inputs of contaminants of emerging concern (CECs) of wastewater origin. These WWTPs were recently upgraded to tertiary treatment for phosphorus removal...
December 2016: Environmental Monitoring and Assessment
https://www.readbyqxmd.com/read/27888753/gastrointestinal-bleeding-and-intracranial-hemorrhage-in-concomitant-users-of-warfarin-and-antihyperlipidemics
#15
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/27867278/effect-of-methanolic-leaf-extract-of-talinum-triangulare-jacq-willd-on-biochemical-parameters-in-diet-induced-dyslipidemia-wistar-rats
#16
Olubukola Sinbad Olorunnisola, Adewale Adetutu, Anthony Jide Afolayan, Abiodun Olusoji Owoade
OBJECTIVE: To investigate the effect of methanolic leaf extract of Talinum triangulare on hematological parameters, enzymatic and non-enzymatic antioxidant status, and serum lipid in Wistar rats fed standard laboratory, or 2% cholesterol-enrich diet. MATERIAL AND METHODS: Wistar rats (180-210g) divided into six groups of six animals (males) each were fed 2% cholesterol-enriched diet and orally treated with 0.9% saline or extract of Talinum triangulare (250, 500, and 1000 mg/kg per body weight) daily for eight weeks...
October 2016: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/27858342/physiologically-based-pharmacokinetic-pbpk-modeling-of-pitavastatin-and-atorvastatin-to-predict-drug-drug-interactions-ddis
#17
Peng Duan, Ping Zhao, Lei Zhang
BACKGROUND: The disposition of statins varies and involves both metabolizing enzymes and transporters, making predictions of statin drug-drug interactions (DDIs) challenging. Physiologically based pharmacokinetic (PBPK) models have, however, demonstrated ability to predict complex DDIs. OBJECTIVE: In this study, PBPK models of two statins (pitavastatin and atorvastatin) were developed and applied to predict pitavastatin and atorvastatin associated DDIs. METHOD: Pitavastatin and atorvastatin PBPK models were developed using in vitro and human pharmacokinetic data in a population-based PBPK software (SimCYP(®)) by considering the contribution of both metabolizing enzymes and transporters to their overall pharmacokinetics...
November 17, 2016: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27836351/characterizing-pharmaceutical-personal-care-product-and-hormone-contamination-in-a-karst-aquifer-of-southwestern-illinois-usa-using-water-quality-and-stream-flow-parameters
#18
L K Dodgen, W R Kelly, S V Panno, S J Taylor, D L Armstrong, K N Wiles, Y Zhang, W Zheng
Karst aquifers are drinking water sources for 25% of the global population. However, the unique geology of karst areas facilitates rapid transfer of surficial chemicals to groundwater, potentially contaminating drinking water. Contamination of karst aquifers by nitrate, chloride, and bacteria have been previously observed, but little knowledge is available on the presence of contaminants of emerging concern (CECs), such as pharmaceuticals. Over a 17-month period, 58 water samples were collected from 13 sites in the Salem Plateau, a karst region in southwestern Illinois, United States...
February 1, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/27835930/master-autophagy-regulator-transcription-factor-eb-regulates-cigarette-smoke-induced-autophagy-impairment-and-chronic-obstructive-pulmonary-disease-emphysema-pathogenesis
#19
Manish Bodas, Neel Patel, David Silverberg, Kyla Walworth, Neeraj Vij
AIMS: Recent studies have shown that cigarette smoke (CS)-induced oxidative stress impairs autophagy, resulting in aggresome-formation that correlates with severity of chronic obstructive pulmonary disease (COPD)-emphysema, although the specific step in autophagy pathway that is impaired is unknown. Hence, in this study, we aimed to evaluate the role of master autophagy transcription factor EB (TFEB) in CS-induced COPD-emphysema pathogenesis. RESULTS: We first observed that TFEB accumulates in perinuclear spaces as aggresome-bodies in COPD lung tissues of tobacco smokers and severe emphysema subjects, compared with non-emphysema or nonsmoker controls...
February 1, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27835067/effect-of-the-lipid-regulator-gemfibrozil-in-the-cladocera-daphnia-magna-at-different-temperatures
#20
Beatriz Salesa, María D Ferrando, María J Villarroel, Encarna Sancho
In the present study, an ecotoxicological approach to the evaluation of Gemfibrozil (GEM) as an emerging organic pollutant was done. In order to assess its toxicity, tests were conducted using the cladocera Daphnia magna. Experiments were carried out at 22°C and 28°C. EC50, feeding behavior, and chronic toxicity tests (21 days) were evaluated in D. magna exposed to GEM as well as cholesterol levels at 21-day chronic exposure. D. magna GEM EC50 values (24 h) in our experimental conditions were 148.75 and 116...
February 23, 2017: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
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