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https://www.readbyqxmd.com/read/29140290/ameliorative-effects-of-grape-seed-proanthocyanidin-extract-on-growth-performance-immune-function-antioxidant-capacity-biochemical-constituents-liver-histopathology-and-aflatoxin-residues-in-broilers-exposed-to-aflatoxin-b%C3%A2
#1
Shahid Ali Rajput, Lvhui Sun, Niya Zhang, Mahmoud Mohamed Khalil, Xin Gao, Zhao Ling, Luoyi Zhu, Farhan Anwar Khan, Jiacai Zhang, Desheng Qi
Aflatoxicosis is a grave threat to the poultry industry. Dietary supplementation with antioxidants showed a great potential in enhancing the immune system; hence, protecting animals against aflatoxin B₁-induced toxicity. Grape seed proanthocyanidin extract (GSPE) one of the most well-known and powerful antioxidants. Therefore, the purpose of this research was to investigate the effectiveness of GSPE in the detoxification of AFB₁ in broilers. A total of 300 one-day-old Cobb chicks were randomly allocated into five treatments of six replicates (10 birds per replicate), fed ad libitum for four weeks with the following dietary treatments: 1...
November 15, 2017: Toxins
https://www.readbyqxmd.com/read/29139224/a-polyelectrolyte-multilayer-platform-for-investigating-growth-factor-delivery-modes-in-human-liver-cultures
#2
Christine Lin, Raimundo Romero, Lioudmila V Sorokina, Kimberly R Ballinger, Laura W Place, Matt J Kipper, Salman R Khetani
Polyelectrolyte multilayers (PEMs) of chitosan and heparin are useful for mimicking growth factor (GF) binding to extracellular matrix (ECM) as in vivo. Here, we developed a PEM platform for delivering bound/adsorbed GFs to monocultures of primary human hepatocytes (PHHs) and PHH/non-parenchymal cell (NPC) co-cultures, which are useful for drug development and regenerative medicine. The effects of ECM protein coating (collagen I, fibronectin, and Matrigel®) and terminal PEM layer on PHH attachment/functions were determined...
November 15, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29138984/11%C3%AE-hydroxysteroid-dehydrogenases-and-hypertension-in-the-metabolic-syndrome
#3
REVIEW
Matthew A Bailey
The metabolic syndrome describes a clustering of risk factors-visceral obesity, dyslipidaemia, insulin resistance, and salt-sensitive hypertension-that increases mortality related to cardiovascular disease, type 2 diabetes, cancer, and non-alcoholic fatty liver disease. The prevalence of these concurrent comorbidities is ~ 25-30% worldwide, and metabolic syndrome therefore presents a significant global public health burden. Evidence from clinical and preclinical studies indicates that glucocorticoid excess is a key causal feature of metabolic syndrome...
November 14, 2017: Current Hypertension Reports
https://www.readbyqxmd.com/read/29138287/clopidogrel-carboxylic-acid-glucuronidation-is-mediated-mainly-by-ugt2b7-ugt2b4-and-ugt2b17-implications-for-pharmacogenetics-and-drug-drug-interactions
#4
Helina Kahma, Anne M Filppula, Mikko Neuvonen, E Katriina Tarkiainen, Aleksi Tornio, Mikko T Holmberg, Matti K Itkonen, Moshe Finel, Pertti J Neuvonen, Mikko Niemi, Janne T Backman
The antiplatelet drug clopidogrel is metabolized to an acyl-β-D-glucuronide, which causes time-dependent inactivation of CYP2C8. Our aim was to characterize the UDP-glucuronosyltransferase (UGT) enzymes that are responsible for the formation of clopidogrel acyl-β-D-glucuronide. Kinetic analyses and targeted inhibition experiments were performed using pooled human liver and intestine microsomes (HLM and HIM, respectively) and selected human recombinant UGTs based on preliminary screening. The effects of relevant UGT polymorphisms on the pharmacokinetics of clopidogrel were evaluated in 106 healthy volunteers...
November 14, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29138019/a-patient-with-severe-fever-with-thrombocytopenia-syndrome-and-hemophagocytic-lymphohistiocytosis-associated-involvement-of-the-central-nervous-system
#5
Kaneko Masahiko, Shikata Hisaharu, Matsukage Shoichi, Maruta Masaki, Shinomiya Hiroto, Suzuki Tadaki, Hasegawa Hideki, Shimojima Masayuki, Saijo Masayuki
Severe fever with thrombocytopenia syndrome (SFTS), a severe infectious disease caused by novel bunyavirus, SFTS virus (SFTSV), is endemic to China, Korea, and Japan. Most SFTS patients show abnormalities in consciousness. Pathological findings in the central nervous system (CNS) of SFTS patients are not reported. A 53-year-old Japanese man was admitted to Uwajima City Hospital with an 8-day history of fever and diarrhea. Laboratory tests revealed leukopenia, thrombocytopenia, and liver enzyme elevation. He was diagnosed as having severe fever with thrombocytopenia syndrome (SFTS) following detection of the SFTSV genome in his blood...
November 11, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/29137181/structure-and-functional-analysis-of-promoters-from-two-liver-isoforms-of-cpt-i-in-grass-carp-ctenopharyngodon-idella
#6
Yi-Huan Xu, Zhi Luo, Kun Wu, Yao-Fang Fan, Wen-Jing You, Li-Han Zhang
Carnitine palmitoyltransferase I (CPT I) is a key enzyme involved in the regulation of lipid metabolism and fatty acid β-oxidation. To understand the transcriptional mechanism of CPT Iα1b and CPT Iα2a genes, we cloned the 2695-bp and 2631-bp regions of CPT Iα1b and CPT Iα2a promoters of grass carp (Ctenopharyngodon idella), respectively, and explored the structure and functional characteristics of these promoters. CPT Iα1b had two transcription start sites (TSSs), while CPT Iα2a had only one TSS. DNase I foot printing showed that the CPT Iα1b promoter was AT-rich and TATA-less, and mediated basal transcription through an initiator (INR)-independent mechanism...
November 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29137040/a-multicenter-open-label-phase-iii-study-of-abcertin-in-gaucher-disease
#7
Beom Hee Lee, Ahmed Fathy Abdalla, Jin-Ho Choi, Amal El Beshlawy, Gu-Hwan Kim, Sun Hee Heo, Ahmed Megahed Hassan Megahed, Mona Abdel Latif Elsayed, Tarik El-Sayed Mohammad Barakat, Khaled Mohamed Abd El-Azim Eid, Mona Hassan El-Tagui, Mona Mohamed Hamdy Mahmoud, Ekram Fateen, June-Young Park, Han-Wook Yoo
BACKGROUND: Gaucher disease (GD) is caused by a deficiency in the lysosomal enzyme glucocerebrosidase. Enzyme replacement therapy (ERT) is recommended for clinical improvement. METHODS: The efficacy and safety of a new imiglucerase, Abcertin, were assessed in 7 Egyptian patients with treatment-naïve type 1 GD. Each patient was administered a biweekly 60 U/kg dose of Abcertin for 6 months. The primary endpoint was the change in hemoglobin concentration. The secondary endpoints were changes from baseline in platelet counts, spleen and liver volumes, biomarker levels, skeletal parameters, and bone mineral density...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29136956/antagonistic-effect-of-oxytocin-and-tacrolimus-combination-on-adipose-tissue-derived-mesenchymal-stem-cells-antagonistic-effect-of-oxytocin-and-tacrolimus-antagonistic-effect-of-oxytocin-and-tacrolimus
#8
Gozde Sir, Bakiye Goker Bagca, Gurkan Yigitturk, Turker Cavusoglu, Cigir Biray Avci, Cumhur Gunduz, Yigit Uyanikgil
Tacrolimus (FK506) is a chemotherapeutic agent, which uses calcineurin pathway via inhibiting the stimulation of T cells to prevent the formation of immune response in the recipient individual in organ transplants. FK506 is mainly metabolized in the liver by cytochrome P450 enzyme system and is known that it has high toxic effects on different cells. Mesenchymal stem cells (MSCs) have recently gained importance since their potential to be used in cellular therapy and tissue regeneration. In some clinical cases, MSCs are transferred into the patient after the organ transplantations in order to support the treatment...
November 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29136753/-metabolomics-study-of-tris-2-chloroethyl-phosphate-induced-hepaotoxicity-and-nephrotoxicity-in-sprague-dawley-rats
#9
W Q Yang, F Zhao, L Li, Y J Fang
Objective: To discuss the potential toxic target organ and the toxic effects and mechanisms of tris (2-chloroethyl) phosphate (TCEP) on SD rats. Methods: 40 female SD rats weaning from milk for 21 days, weighted (50±2.3)g were selected as subjects and marked by the weight. They were randomly divided into 4 groups, namely control group, 50 (L), 100 (M) and 250 (H) mg·kg(-1)·d(-1) dose of TCEP group. Each group has 10 rats, and administrated the corresponding dose of drug or vehicle by mouth, quaque die for 60 days...
November 6, 2017: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/29136681/assessment-of-multiple-cytochrome-p450-activities-in-metabolically-inactivated-human-liver-microsomes-and-roles-of-p450-2c-isoforms-in-reaction-phenotyping-studies
#10
Norie Murayama, Kanako Yajima, Mikiko Hikawa, Kanami Shimura, Yu Ishii, Masaki Takada, Yasuhiro Uno, Masahiro Utoh, Kazuhide Iwasaki, Hiroshi Yamazaki
The fraction of substrate metabolized (fm ) can be used to estimate drug interactions and can be determined by comparison of the intrinsic clearances (CLint ) of victim drugs obtained from inhibited and uninhibited hepatic enzymes. Commercially available human liver microsomes were recently developed in which one cytochrome P450 (P450) isoform is selectively inactivated. These inactivated liver microsomes were used to evaluate the roles of P450 2C isoforms in the depletion and oxidation of probe substrates...
November 14, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29136336/effect-of-polymorphisms-on-the-pharmacokinetics-pharmacodynamics-and-safety-of-sertraline-in-healthy-volunteers
#11
Miriam Saiz-Rodríguez, Carmen Belmonte, Manuel Román, Dolores Ochoa, Dora Koller, María Talegón, María C Ovejero-Benito, Rosario López-Rodríguez, Teresa Cabaleiro, Francisco Abad-Santos
Sertraline is a selective serotonin reuptake inhibitor (SSRI) widely metabolized in the liver by cytochrome P450 (CYP) enzymes. Besides, it is a P-glycoprotein substrate. Moreover, serotonin transporters and serotonin receptors are involved in its efficacy and safety. The aim of the present study was to evaluate the role of polymorphisms of metabolizing enzymes, transporters and receptors on the pharmacokinetics, pharmacodynamics and tolerability of sertraline in healthy volunteers. Forty-six healthy volunteers (24 men and 22 women) receiving a 100-mg single oral dose of sertraline were genotyped for 17 genetic variants of CYP enzymes (CYP2B6, CYP2C9, CYP2C19, CYP2D6), ATP binding cassette subfamily B member 1 (ABCB1), Solute carrier family 6 member 4 (SLC6A4), 5-Hydroxytryptamine receptor 2A (HTR2A) and 5-Hydroxytryptamine receptor 2C (HTR2C) genes...
November 14, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29134775/changes-in-sensitivity-to-the-effects-of-atrazine-on-the-luteinizing-hormone-surge-in-female-sprague-dawley-rats-after-repeated-daily-doses-correlation-with-liver-enzyme-expression
#12
Charles B Breckenridge, Chad D Foradori, Pragati Sawhney Coder, James W Simpkins, Robert L Sielken, Robert J Handa
BACKGROUND: Atrazine suppression of the LH surge slowly develops over time and peaks after 4 days; sensitivity to atrazine decreases after 8 or 14 days of dosing. Adaptation of the LH response was correlated with increased phase I and phase II liver enzyme activity/expression. METHODS: The effect of atrazine on the LH surge was evaluated in female Sprague-Dawley rats administered 100 mg/kg/day atrazine by gavage for 1, 2, 3, or 4 consecutive days or 6.5, 50, or 100 mg/kg/day atrazine for 4, 8, or 14 days...
November 14, 2017: Birth defects research
https://www.readbyqxmd.com/read/29134411/distinct-roles-of-ecto-nucleoside-triphosphate-diphosphohydrolase-2-ntpdase2-in-liver-regeneration-and-fibrosis
#13
Linda Feldbrügge, Z Gordon Jiang, Eva Csizmadia, Shuji Mitsuhashi, Stephanie Tran, Eric U Yee, Sonja Rothweiler, Kahini A Vaid, Jean Sévigny, Moritz Schmelzle, Yury V Popov, Simon C Robson
Ecto-nucleoside triphosphate diphosphohydrolases (E-NTPDases) are cell surface-located transmembrane ecto-enzymes of the CD39 superfamily which regulate inflammation and tissue repair by catalyzing the phosphohydrolysis of extracellular nucleotides and modulating purinergic signaling. In the liver, NTPDase2 is reportedly expressed on portal fibroblasts, but its functional role in regulating tissue regeneration and fibrosis is incompletely understood. Here, we studied the role of NTPDase2 in several models of liver injury using global knockout mice...
November 13, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/29134244/modulation-of-cyp3a-enzyme-activity-by-diosmin-and-its-consequence-on-carbamazepine-pharmacokinetics-in-rats
#14
Satish Kumar Bedada, Prasad Neerati
Diosmin is a widely used flavonoid for the treatment of varicose veins and hemorrhoids. Epileptic patients with hemorrhoids and varicose veins may use diosmin along with carbamazepine (CBZ) therapy, which leads to pharmacokinetic interaction between diosmin and CBZ. Therefore, the present study was performed to evaluate the effect of diosmin on the pharmacokinetics of CBZ in rats. Diosmin-mediated altered CYP3A enzyme activity in human and rat liver microsomes was examined using CYP3A dependent erythromycin N-demethylase assay...
November 14, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29133569/efficacy-of-tilorone-dihydrochloride-against-ebola-virus-infection
#15
Sean Ekins, Mary A Lingerfelt, Jason E Comer, Alexander N Freiberg, Jon C Mirsalis, Kathleen O'Loughlin, Anush Harutyunyan, Claire McFarlane, Carol E Green, Peter B Madrid
Tilorone dihydrochloride (tilorone) is a small-molecule, orally bioavailable drug that is used clinically as an antiviral outside of the US. A machine learning model trained on anti-Ebola virus (EBOV) screening data previously identified tilorone as a potent in vitro EBOV inhibitor, making it a candidate for the treatment of Ebola virus disease (EVD). In the present study, a series of in vitro ADMET (absorption, distribution, metabolism, excretion, toxicity) assays demonstrated the drug has excellent solubility, high Caco-2 permeability, was not a P-glycoprotein substrate and had no inhibitory activity against five human CYP450 enzymes (3A4, 2D6, 2C19, 2C9 and 1A2)...
November 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29133031/chloroquine-upregulates-trail-trailr2-expression-and-potentiates-doxorubicin-anti-tumor-activity-in-thioacetamide-induced-hepatocellular-carcinoma-model
#16
Sahar A Helmy, Mohamed El-Mesery, Amro El-Karef, Laila A Eissa, Amal M El Gayar
Impaired apoptosis and systemic toxicity of chemotherapeutic drugs make cancer treatment suboptimal. Thus, there is urgency for drug repurposing which facilitates discovery of safe and effective combination therapy. This study aimed to evaluate chloroquine's (CQ) ability to trigger TRAIL/TRAILR2 apoptotic pathway in thioacetamide (TAA)-induced hepatocellular carcinoma (HCC) either alone or in combination with doxorubicin (DOX). Moreover, its ability to attenuate DOX-induced cardiotoxicity was investigated. TAA was injected in male Sprague Dawely rats (200 mg/kg; ip; 2 times/week) for 16 weeks...
November 10, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29132905/purification-and-biochemical-characterization-of-a-22-kda-stable-cysteine-like-protease-from-the-excretory-secretory-product-of-the-liver-fluke-fasciola-hepatica-by-using-conventional-techniques
#17
Ahmed Hemici, Roumaila Sabrina Benerbaiha, Dalila Bendjeddou
This study describes the purification and characterization of a stable protease activity isolated from Fasciola hepatica adult worms maintained in vitro by employing acetone precipitation (40-60%) followed by a gel filtration through Sephadex G-100 and DEAE- cellulose ion exchange column. Through this three-step purification, the enzyme was purified 11-fold with a specific activity of 1893.9U/mg and 31.5% recovery. After the final ultrafiltration step, the purification fold was increased up to 13.1 and the overall activity yield reached a rate of 18...
October 28, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29132522/nonalcoholic-fatty-liver-disease
#18
REVIEW
Patrick H Sweet, Teresa Khoo, Steven Nguyen
Nonalcoholic fatty liver disease (NAFLD) defines a condition of hepatic steatosis with or without hepatic injury. NAFLD is increasing in prevalence worldwide and presents a public health burden. Most patients are asymptomatic, although some present with fatigue and right upper quadrant pain. NAFLD is discovered incidentally when patients have elevated liver enzymes or fatty liver is seen on imaging modalities. Imaging studies can confirm fatty deposits in the liver, but needle biopsy is needed to determine degree of inflammation...
December 2017: Primary Care
https://www.readbyqxmd.com/read/29132372/hepatitis-b-virus-inhibits-the-in-vivo-and-in-vitro-synthesis-and-secretion-of-apolipoprotein-c3
#19
Chengliang Zhu, Hengcheng Zhu, Hui Song, Limin Xu, Longxuan Li, Fang Liu, Xinghui Liu
BACKGROUND: Hepatitis B virus (HBV) infection in the body can damage liver cells and cause disorders in blood lipid metabolism. Apolipoprotein C3 (ApoC3) plays an important role in the regulation of lipid metabolism, but no study on the HBV regulation of ApoC3 has been reported. This purpose of this study was to investigate the effect of HBV on ApoC3 expression and its regulatory mechanism. METHODS: The expression levels of ApoC3 mRNA and protein in the human hepatoma cell lines HepG2 and HepG2...
November 13, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/29132130/effect-of-huagantongluofang-a-chinese-traditional-medicine-in-hepatic-fibrogenesis-in-a-mouse-model-of-biliary-cirrhosis
#20
Ji Xuan, Wei Wen, Yong Wang, Feng Wang, Hua-Bing Xu, Mei Shao, Ya Yang, Yao-Zhou Tian
BACKGROUND: Biliary cirrhosis (BC) is a chronic cholestatic liver disease, in which hepatic fibrosis is an early symptom. This study aimed to identify the biological function and the therapeutic effect of a Chinese traditional medicine, HuaGanTongLuoFang (HGTLF), in a mouse model of BC. METHODS: The mice (n = 72) were randomly divided into a sham group (n =12) and BC group (n = 60). The animals in the BC group were then randomly divided into five groups (n = 12 in each) and treated with three different doses of HGTLF, ureodeoxycholic acid (UDCA), or normal saline (the model group)...
November 13, 2017: Cellular Physiology and Biochemistry
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