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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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-tfeb-regulates-cigarette-smoke-induced-autophagy-impairment-and-copd-emphysema-pathogenesis
#13
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 the severity of COPD-emphysema. Although, specific step in autophagy-pathway that is impaired is unknown. Hence, in this study we aimed to evaluate the role of master autophagy-regulator and transcription factor-EB (TFEB) in CS-induced COPD-emphysema pathogenesis. RESULTS: We first observed that TFEB-accumulates in the peri-nuclear spaces of the COPD lung tissues of tobacco-smokers and severe-emphysema subjects...
November 11, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27835067/effect-of-the-lipid-regulator-gemfibrozil-in-the-cladocera-daphnia-magna-at-different-temperatures
#14
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...
November 11, 2016: Journal of Environmental Science and Health. Part A, Toxic/hazardous Substances & Environmental Engineering
https://www.readbyqxmd.com/read/27686305/pioglitazone-improves-serum-lipid-profile-in-diet-induced-hyperlipidaemic-non-diabetic-rats
#15
Mazhar Hussian, Abdul Qudoos Arain, Sadia Chiragh
OBJECTIVE: To evaluate the anti-dyslipidaemic effects of pioglitazone in diet-induced non-diabetic hyperlipidaemic rats and to compare them with gemfibrozil. METHODS: This comparative animal study was conducted at the Postgraduate Medical Institute, Lahore, Pakistan, from July to September 2011, and comprised Sprague Dawley albino rats divided into three equal groups. Initially all three groups were given high-lipid diet containing cholesterol 1.5g, coconut oil 8ml and sodium cholate 1...
October 2016: JPMA. the Journal of the Pakistan Medical Association
https://www.readbyqxmd.com/read/27665778/transcriptome-analyses-demonstrate-that-peroxisome-proliferator-activated-receptor-%C3%AE-ppar%C3%AE-activity-of-an-ultraviolet-absorber-2-2-hydroxy-3-5-di-tert-butylphenyl-benzotriazole-as-possible-mechanism-of-their-toxicity-and-the-gender-differences
#16
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
https://www.readbyqxmd.com/read/27648490/transporter-mediated-hepatic-uptake-plays-an-important-role-in-the-pharmacokinetics-and-drug-drug-interactions-of-montelukast
#17
M V Varma, E Kimoto, R Scialis, Y Bi, J Lin, H Eng, A S Kalgutkar, A F El-Kattan, A D Rodrigues, L M Tremaine
Montelukast, a leukotriene receptor antagonist commonly prescribed for treatment of asthma, is primarily metabolized by cytochrome P450 (CYP)2C8, and has been suggested as a probe substrate for investigating CYP2C8 activity in vivo. We evaluated the quantitative role of hepatic uptake transport in its pharmacokinetics and drug-drug interactions (DDIs). Montelukast was characterized with significant active uptake in human hepatocytes, and showed affinity towards organic anion transporting polypeptides (OATPs) in transfected cell systems...
September 20, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27642087/quantitative-prediction-of-drug-drug-interactions-involving-inhibitory-metabolites-in-drug-development-how-can-physiologically-based-pharmacokinetic-modeling-help
#18
I E Templeton, Y Chen, J Mao, J Lin, H Yu, S Peters, M Shebley, M V Varma
This subteam under the Drug Metabolism Leadership Group (Innovation and Quality Consortium) investigated the quantitative role of circulating inhibitory metabolites in drug-drug interactions using physiologically based pharmacokinetic (PBPK) modeling. Three drugs with major circulating inhibitory metabolites (amiodarone, gemfibrozil, and sertraline) were systematically evaluated in addition to the literature review of recent examples. The application of PBPK modeling in drug interactions by inhibitory parent-metabolite pairs is described and guidance on strategic application is provided...
September 19, 2016: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/27624558/the-enhanced-atorvastatin-hepatotoxicity-in-diabetic-rats-was-partly-attributed-to-the-upregulated-hepatic-cyp3a-and-slco1b1
#19
Nan Shu, Mengyue Hu, Zhaoli Ling, Peihua Liu, Fan Wang, Ping Xu, Zeyu Zhong, Binbin Sun, Mian Zhang, Feng Li, Qiushi Xie, Xiaodong Liu, Li Liu
Liver injury is a common adverse effect of atorvastatin. This study aimed to investigate atorvastatin-induced hepatotoxicity in diabetic rats induced by high-fat diet combined with streptozotocin. The results showed that 40 mg/kg atorvastatin was lethal to diabetic rats, whose mean survival time was 6.2 days. Severe liver injury also occurred in diabetic rats treated with 10 mg/kg and 20 mg/kg atorvastatin. The in vitro results indicated that atorvastatin cytotoxicity in hepatocytes of diabetic rats was more severe than normal and high-fat diet feeding rats...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27553001/phytotoxicity-of-15-common-pharmaceuticals-on-the-germination-of-lactuca-sativa-and-photosynthesis-of-chlamydomonas-reinhardtii
#20
Ma Rosa Pino, Selene Muñiz, Jonatan Val, Enrique Navarro
Pharmaceuticals reach terrestrial environments through the application of treated wastewaters and biosolids to agricultural soils. We have investigated the toxicity of 15 common pharmaceuticals, classified as nonsteroidal anti-inflammatory drugs (NSAIDs), blood lipid-lowering agents, β-blockers and antibiotics, in two photosynthetic organisms. Twelve pharmaceuticals caused inhibitory effects on the radicle and hypocotyl elongation of Lactuca sativa seeds. The EC50 values obtained were in the range of 170-5656 mg L(-1) in the case of the radicle and 188-4558 mg L(-1) for the hypocotyl...
August 24, 2016: Environmental Science and Pollution Research International
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