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Xiujuan Kong, Zihao Wu, Ziran Ren, Kaiheng Guo, Shaodong Hou, Zhechao Hua, Xuchun Li, Jingyun Fang
Degradation of three lipid regulators, i.e., gemfibrozil, bezafibrate and clofibric acid, by a UV/chlorine treatment was systematically investigated. The chlorine oxide radical (ClO• ) played an important role in the degradation of gemfibrozil and bezafibrate with second-order rate constants of 4.2 (±0.3) × 108  M-1  s-1 and 3.6 (±0.1) × 107  M-1  s-1 , respectively, whereas UV photolysis and the hydroxyl radical (HO• ) mainly contributed to the degradation of clofibric acid. The first-order rate constants (k') for the degradation of gemfibrozil and bezafibrate increased linearly with increasing chlorine dosage, primarily due to the linear increase in the ClO• concentration...
March 6, 2018: Water Research
Yu-Fei Ni, Hao Wang, Qiu-Yan Gu, Fei-Ying Wang, Ying-Jie Wang, Jin-Liang Wang, Bo Jiang
Major depressive disorder has become one of the most serious neuropsychiatric disorders worldwide. However, currently available antidepressants used in clinical practice are ineffective for a substantial proportion of patients and always have side effects. Besides being a lipid-regulating agent, gemfibrozil is an agonist of peroxisome proliferator-activated receptor-α (PPAR-α). We investigated the antidepressant effects of gemfibrozil on C57BL/6J mice using the forced swim test (FST) and tail suspension test (TST), as well as the chronic unpredictable mild stress (CUMS) model of depression...
March 1, 2018: Journal of Psychopharmacology
Katherine E Greenstein, Julia Lew, Eric R V Dickenson, Eric C Wert
The evolving demands of drinking water treatment necessitate processes capable of removing a diverse suite of contaminants. Biofiltration can employ biotransformation and sorption to remove various classes of chemicals from water. Here, pilot-scale virgin anthracite-sand and previously used biological activated carbon (BAC)-sand dual media filters were operated for ∼250 days to assess removals of 0.4 mg/L ammonia as nitrogen, 50-140 μg/L manganese, and ∼100 ng/L each of trace organic compounds (TOrCs) spiked into pre-ozonated Colorado River water...
February 19, 2018: Chemosphere
Shamaila Fraz, Abigail H Lee, Joanna Y Wilson
Gemfibrozil (GEM) and carbamazepine (CBZ) are two environmentally relevant pharmaceuticals and chronic exposure of fish to these compounds has decreased androgen levels and fish reproduction in laboratory studies. The main focus of this study was to examine the effects of GEM and CBZ on testicular steroid production, using zebrafish as a model species. Chronic water borne exposures of adult zebrafish to 10 μg/L of GEM and CBZ were conducted and the dosing was confirmed by chemical analysis of water as 17...
February 10, 2018: Aquatic Toxicology
Jianchao Liu, Xiaoxiang Dan, Guanghua Lu, Jie Shen, Donghai Wu, Zhenhua Yan
Pharmaceutically active compounds (PhACs) recently have been recognized to constitute a health risk for aquatic ecosystems. The major pathways of PhACs to enter the aquatic environment are excretion and discharge of effluents through sewage treatment plants (STPs). The occurrence, bioaccumulation and risk assessment of lipophilic PhACs, including erythromycin, ketoconazole, indomethacin, diclofenac, gemfibrozil, bezafibrate, propranolol, carbamazepine, sertraline and 17α-ethinylestradiol were investigated in a river that receives effluents from STP...
February 21, 2018: Ecotoxicology and Environmental Safety
Kristine M Hammill, Shamaila Fraz, Abigail H Lee, Joanna Y Wilson
The effects of parental exposure to pharmaceuticals on sexual differentiation in F1 offspring were examined in zebrafish (Danio rerio). Adult zebrafish were exposed to 0 or 10 µg/L of carbamazepine or gemfibrozil for 6 weeks and bred in pairwise crosses to generate 7 distinct lineages. Lineages were formed with both parents from the same treatment group or with only one parent exposed, to delineate between maternal and paternal effects. The F1 offspring from each lineage were reared in clean water and sampled at 45 and 60 days post fertilization (dpf)...
February 24, 2018: Environmental Toxicology and Chemistry
Kosuke Doki, Adam S Darwich, Brahim Achour, Aleksi Tornio, Janne T Backman, Amin Rostami-Hodjegan
AIMS: Statistically significant positive correlations are reported for the abundance of hepatic drug-metabolising enzymes. We investigate, as an example, the impact of CYP3A4-CYP2C8 inter-correlation on the predicted inter-individual variabilities of clearance and drug-drug interactions (DDIs) for repaglinide using physiologically-based pharmacokinetic (PBPK) modelling. METHODS: PBPK modelling and simulation was employed using Simcyp Simulator (v15.1). Virtual populations were generated assuming inter-correlations between hepatic CYP3A4-CYP2C8 abundances derived from observed values in 24 human livers...
January 30, 2018: British Journal of Clinical Pharmacology
Drayton A Hammond, Laura Finlay
Hypertriglyceridemia is the third most common worldwide cause of acute pancreatitis. Resolving the underlying etiology is imperative for optimal management. This is especially true with regard to hypertriglyceridemia, as this etiology may cause more severe acute pancreatitis and worse symptoms than other causes of the disease. Many pharmacological treatment options for hypertriglyceridemia-induced acute pancreatitis (HTGP) have been proposed; however, the safety and efficacy for specific treatment regimens remain nebulous...
November 2017: Hospital Pharmacy
Jin-Zi Ji, Bei-Bei Huang, Tong-Tong Gu, Ting Tai, Huan Zhou, Yu-Meng Jia, Qiong-Yu Mi, Meng-Ran Zhang, Hong-Guang Xie
Clopidogrel is predominantly hydrolyzed to clopidogrel carboxylic acid (CCA) by carboxylesterase 1, and subsequently CCA is glucuronidated to clopidogrel aryl glucuronide (CAG) by uridine diphosphate-glucuronosyltransferases (UGTs); however, the UGT isoenzymes glucuronidating CCA remain unidentified to date. In this study, the glucuronidation of CCA was screened with pooled human liver microsomes (HLMs) and 7 human recombinant UGT (rUGT) isoforms. Results indicated that rUGT2B7 exhibited the highest catalytical activity for the CCA glucuronidation as measured with a mean Vmax value of 120...
December 14, 2017: Biopharmaceutics & Drug Disposition
Delia Teresa Sponza, Gökçe Güney
In this study, the degradations of 2,3,4,5,6-pentabromotoluene (PBT), 2,3,4,5,6-pentabromoethyl benzene (PBEB), triclosan (TCS) and gemfibrozil (GFZ) in raw hospital wastewater were investigated with cerium (IV) oxide and titanium (IV) oxide nanoparticles considering the mechanisms of adsorption, photolysis, and photocatalysis with UV-C lamps. The effects of nano-CeO2 and nano-TiO2 concentrations, irradiation times, UV light powers and hospital wastewater pH on the photodegradation yields of micropollutants namely PBT, PBEB, TCS and GFZ were investigated throughout photocatalysis...
November 2017: Water Science and Technology: a Journal of the International Association on Water Pollution Research
Dylan Steinkey, Ebrahim Lari, Samuel G Woodman, Kim H Luong, Charles S Wong, Greg G Pyle
Gemfibrozil, a common lipid regulator, enters aquatic environments through treated municipal wastewater effluent that fails to remove it completely from effluent streams. When exposed to gemfibrozil concentrations of 50, 500, 5,000, and 50,000 ng L(-1), Daphnia magna showed increased lipid reserves by 14-21% (significant at 500 ng L(-1)), increased length by 9-13% (significant at 50 ng L(-1)), increased mass by 6-13% (significant at 50 ng L(-1)) and increased neonate production by 57-74% (significant at 50 ng L(-1))...
October 31, 2017: Chemosphere
Kálmán Benke, Csaba Mátyás, Alex Ali Sayour, Attila Oláh, Balázs Tamás Németh, Mihály Ruppert, Gábor Szabó, Gábor Kökény, Eszter Mária Horváth, István Hartyánszky, Zoltán Szabolcs, Béla Merkely, Tamás Radovits
While heart transplantation (HTX) is the definitive therapy of heart failure, donor shortage is emerging. Pharmacological activation of soluble guanylate cyclase (sGC) and increased cGMP-signalling have been reported to have cardioprotective properties. Gemfibrozil has recently been shown to exert sGC activating effects in vitro. We aimed to investigate whether pharmacological preconditioning of donor hearts with gemfibrozil could protect against ischemia/reperfusion injury and preserve myocardial function in a heterotopic rat HTX model...
October 27, 2017: Scientific Reports
Ying Tang, Lu-Lu Guo, Cheng-Yang Hong, Yong-Xin Bing, Zhen-Cheng Xu
A long term investigation, which covered 10 sampling campaigns over three years, was performed to evaluate the occurrence, removal and risk of ten pharmaceuticals in two full-scale sewage treatment plants (STPs) in Guangdong, South China. Target pharmaceuticals except for clofibrate and ibuprofen were detected in every sample, with mean concentrations of 12.5-685.6 ng/L and 7.9-130.3 ng/L in the influent and effluent, respectively. Salicylic acid was the most abundant compound in both the influents and effluents in the two STPs...
October 25, 2017: Environmental Technology
W A Banks, S A Farr, T S Salameh, M L Niehoff, E M Rhea, J E Morley, A J Hanson, K M Hansen, S Craft
OBJECTIVE: Resistance at the brain receptors for leptin and insulin has been associated with increased feeding, obesity and cognitive impairments. The causal agent for central resistance is unknown but could be derived from the blood. Here we postulate whether hypertriglyceridemia, the major dyslipidemia of the metabolic syndrome, could underlie central leptin and insulin resistance. DESIGN: We used radioactively labeled triglycerides to measure blood-brain barrier (BBB) penetration, western blots to measure receptor activation, and feeding and cognitive tests to assess behavioral endpoints...
October 9, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Methira Siriangkhawut, Patthana Tansakul, Verawan Uchaipichat
Drug-drug interactions are one of the major risk factors associated with statin-induced myopathy. Although simvastatin is widely used in Thailand, studies investigating the prevalence of potential simvastatin-drug interactions (SDIs) and its clinical relevance in Thai population are still limited. We aimed to investigate the prevalence of potential SDIs (phase 1 study) and musculoskeletal adverse effects (AEs) associated with those interactions (phase 2 study). A phase 1 study was retrospectively conducted with outpatients at a 60-bed hospital who received simvastatin between July 1, 2012 and June 30, 2013...
September 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
Min Luo, Manyun Dai, Hante Lin, Minzhu Xie, Jiao Lin, Aiming Liu, Julin Yang
Gemfibrozil is a fibrate drug used widely for dyslipidemia associated with atherosclerosis. Clinically, both gemfibrozil and its phase II metabolite gemfibrozil 1-O-β-glucuronide (gem-glu) are involved in drug-drug interaction (DDI). But the DDI risk caused by gem-glu between human and mice has not been compared. In this study, six volunteers were recruited and took a therapeutic dose of gemfibrozil for 3 days for examination of the gemfibrozil and gem-glu level in human. Male mice were fed a gemfibrozil diet (0...
December 2017: Biopharmaceutics & Drug Disposition
Xavier Humbert, Charles Dolladille, Marion Sassier, Marie-Blanche Valnet-Rabier, Thierry Vial, Emmanuelle Guitton, Annabelle Page, Elodie Sole, Pascal Auriche, Antoine Coquerel, Joachim Alexandre, Sophie Fedrizzi
INTRODUCTION: Several studies have investigated the occurrence of venous thromboembolic events (phlebitis and pulmonary embolism) [VTE] and fibrates. Fibrates could be associated with VTE although published data are contradictory. The objective of this study is to confirm the link between VTE and fibrates. MATERIALS AND METHODS: Retrospective disproportionality analysis (case/non-case method) from observations recorded consecutively in the French pharmacovigilance database between 1985 and 2016...
August 1, 2017: Thérapie
Miriam Biel-Maeso, Rosa María Baena-Nogueras, Carmen Corada-Fernández, Pablo A Lara-Martín
In this study, we have evaluated the occurrence and distribution of 78 pharmaceuticals in different aquatic marine environments from the Gulf of Cadiz (SW Spain) for the first time. The obtained results revealed that pharmaceuticals were present in seawater at total concentrations ranging 61-2133 and 16-189ngL(-1) in coastal and oceanic transects, respectively. Potential marine pollution hotspots were observed in enclosed or semi-enclosed water bodies (Cadiz Bay), showing concentrations that were one or two orders of magnitude higher than in the open ocean...
January 15, 2018: Science of the Total Environment
Sunah Kim, Karen Rossmassler, Corey D Broeckling, Sarah Galloway, Jessica Prenni, Susan K De Long
Limited knowledge of optimal microbial community composition for PPCP biotreatment, and of the microbial phylotypes that drive biotransformation within mixed microbial communities, has hindered the rational design and operation of effective and reliable biological PPCP treatment technologies. Herein, bacterial community composition was investigated as an isolated variable within batch biofilm reactors via comparison of PPCP removals for three distinct inocula. Inocula pre-acclimated to model PPCPs were derived from activated sludge (AS), ditch sediment historically-impacted by wastewater treatment plant effluent (Sd), and material from laboratory-scale soil aquifer treatment (SAT) columns...
November 15, 2017: Water Research
Kaiheng Guo, Zihao Wu, Chii Shang, Bo Yao, Shaodong Hou, Xin Yang, Weihua Song, Jingyun Fang
The UV/chlorine process is an emerging advanced oxidation process (AOP) used for the degradation of micropollutants. However, the radical chemistry of this AOP is largely unknown for the degradation of numerous structurally diverse micropollutants in water matrices of varying quality. These issues were addressed by grouping 34 pharmaceuticals and personal care products (PPCPs) according to the radical chemistry of their degradation in the UV/chlorine process at practical PPCP concentrations (1 μg L(-1)) and in different water matrices...
August 31, 2017: Environmental Science & Technology
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