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https://www.readbyqxmd.com/read/28644885/organic-anion-transporting-polypeptide-1b3-can-form-homo-and-hetero-oligomers
#1
Yuchen Zhang, Kelli H Boxberger, Bruno Hagenbuch
OATP1B3 is a 12 transmembrane domain protein expressed at the basolateral membrane of human hepatocytes where it mediates the uptake of numerous drugs and endogenous compounds. Previous western blot results suggest the formation of OATP1B3 multimers. In order to better understand the function of OATP1B3 under normal physiological conditions, we investigated its oligomerization status. We transiently transfected OATP1B3 with a C-terminal His-, FLAG- or HA-tag in HEK293 cells and used co-immunoprecipitation and a Proximity Ligation Assay to detect interactions between the different constructs...
2017: PloS One
https://www.readbyqxmd.com/read/28642795/why-do-the-youths-in-northeast-india-use-tobacco
#2
Laishram Ladusingh, Preeti Dhillon, Pralip Kumar Narzary
This study is an assessment of the influence of parent's tobacco use on prospective tobacco use trajectories among young offspring. The study is based on unit level data from District Level Household and Facility Survey-4 (2012-2013) comprising 27,706 youths in 15-24 years' age group from northeastern states of India and used multilevel regression to identify the potential risk factors of tobacco consumption. The likelihood of using tobacco was found to be 3.4 and 1.14 times more, respectively, for the youths coresiding with mothers who use tobacco and fathers who use tobacco, in comparison to youths staying with parents not taking tobacco...
2017: Journal of Environmental and Public Health
https://www.readbyqxmd.com/read/28635613/association-of-the-s267f-variant-on-ntcp-gene-and-treatment-response-to-pegylated-interferon-in-patients-with-chronic-hepatitis-b-a-multicentre-study
#3
Kessarin Thanapirom, Sirinporn Suksawatamnuay, Wattana Sukeepaisarnjaroen, Sombat Treeprasertsuk, Tawesak Tanwandee, Phunchai Charatcharoenwitthaya, Satawat Thongsawat, Apinya Leerapun, Teerha Piratvisuth, Rattana Boonsirichan, Chalermrat Bunchorntavakul, Chaowalit Pattanasirigool, Bubpha Pornthisarn, Supoj Tuntipanichteerakul, Ekawee Sripariwuth, Woramon Jeamsripong, Teeranan Sanpanjit, Yong Poovorawan, Piyawat Komolmit
BACKGROUND: Sodium taurocholate co-transporting polypeptide (NTCP) is a cell receptor for hepatitis B virus (HBV). The S267F variant on the NTCP gene is inversely associated with the chronicity of HBV infection, progression to cirrhosis and hepatocellular carcinoma in East Asian populations. This aim of this study was to determine whether the S267F variant was associated with response to pegylated interferon (Peg-IFN) in patients with chronic HBV infection. METHODS: Two hundred and fifty-seven patients with chronic HBV, treated with Peg-IFN for 48 weeks, were identified from 13 tertiary hospitals included in the hepatitis B database of the Thai Association for the Study of the Liver (THASL)...
June 21, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28624460/identification-of-kx2-391-as-an-inhibitor-of-hbv-transcription-by-a-recombinant-hbv-based-screening-assay
#4
Keisuke Harada, Hironori Nishitsuji, Saneyuki Ujino, Kunitada Shimotohno
Antiviral therapies for chronic hepatitis B virus (HBV) infection that are currently applicable for clinical use are limited to nucleos(t)ide analogs targeting HBV polymerase activity and pegylated interferon alpha (PEG-IFN). Towards establishing an effective therapy for HBV related diseases, it is important to develop a new anti-HBV agent that suppresses and eradicates HBV. This study used recombinant HBV encoding NanoLuc to screen anti-HBV compounds from 1827 US Food and Drug Administration approved compounds and identified several compounds that suppressed HBV infection...
June 15, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28605637/hepatitis-b-surface-antigen-on-subviral-particles-reduces-the-neutralizing-effect-of-anti-hbs-antibodies-on-hepatitis-b-viral-particles-in-vitro
#5
Gustaf E Rydell, Kasthuri Prakash, Heléne Norder, Magnus Lindh
During hepatitis B virus (HBV) infections subviral particles (SVP) consisting mainly of hepatitis B surface antigen are present at much higher concentration than viral particles (VP) in serum. To investigate reasons for this excess of SVP production, SVP and VP were fractionated on a Nycodenz gradient and analyzed for HBV infection of HepG2-NTCP cells with and without anti-HBs antibodies. Our findings showed that SVP significantly reduced the neutralization of VP by anti-HBs, while SVP had little effect on viral entry, supporting the assumption that SVP serve as decoy facilitating cell-to-cell spread of HBV in the presence of neutralizing antibodies...
June 9, 2017: Virology
https://www.readbyqxmd.com/read/28603032/%C3%AE-2-adrenergic-receptor-mediated-in-vitro-regulation-of-human-hepatic-drug-transporter-expression-by-epinephrine
#6
Abdullah Mayati, Amélie Moreau, Claire Denizot, Bruno Stieger, Yannick Parmentier, Olivier Fardel
The catecholamine epinephrine is known to repress expression of hepatic drug metabolizing enzymes such as cytochromes P-450. The present study was designed to determine whether epinephrine may also target expression of main hepatic drug transporters, that play a major role in liver detoxification and are commonly coordinately regulated with drug detoxifying enzymes. Treatment of primary human hepatocytes with 10μM epinephrine for 24h repressed mRNA expression of various transporters, such as the sinusoidal influx transporters NTCP, OATP1B1, OATP2B1, OAT2, OAT7 and OCT1 and the efflux transporters MRP2, MRP3 and BSEP, whereas it induced that of MDR1, but failed to alter that of BCRP...
June 8, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28600084/modelling-duodenum-radiotherapy-toxicity-using-cohort-dose-volume-histogram-data
#7
Daniel L P Holyoake, Marianne Aznar, Somnath Mukherjee, Mike Partridge, Maria A Hawkins
BACKGROUND AND PURPOSE: Gastro-intestinal toxicity is dose-limiting in abdominal radiotherapy and correlated with duodenum dose-volume parameters. We aimed to derive updated NTCP model parameters using published data and prospective radiotherapy quality-assured cohort data. MATERIAL AND METHODS: A systematic search identified publications providing duodenum dose-volume histogram (DVH) statistics for clinical studies of conventionally-fractionated radiotherapy. Values for the Lyman-Kutcher-Burman (LKB) NTCP model were derived through sum-squared-error minimisation and using leave-one-out cross-validation...
June 6, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28589066/differences-in-parotid-dosimetry-and-expected-normal-tissue-complication-probabilities-in-whole-brain-radiation-plans-covering-c1-versus-c2
#8
Andrew Orton, John Gordon, Tyler Vigh, Allison Tonkin, George Cannon
OBJECTIVES: There is no consensus standard regarding the placement of the inferior field border in whole brain radiation therapy (WBRT) plans, with most providers choosing to cover the first versus (vs.) second cervical vertebrae (C1 vs. C2). We hypothesize that extending coverage to C2 may increase predicted rates of xerostomia. METHODS: Fifteen patients underwent computed tomography (CT) simulation; two WBRT plans were then produced, one covering C2 and the other covering C1...
May 3, 2017: Curēus
https://www.readbyqxmd.com/read/28555505/comparison-of-dose-distribution-for-head-and-neck-cancer-patients-with-and-without-dose-painting-escalation-during-radiotherapy-realized-with-tomotherapy-unit
#9
Malgorzata Skorska, Tomasz Piotrowski, Adam Ryczkowski
OBJECTIVE: To determine and quantify the percentage dose increase to organs at risk (OARs) with multiple-level dose painting (DP) for patients with head and neck cancer in comparison with standard regimen. METHODS: 12 patients who had undergone fluorine-18 fludeoxyglucose ((18)F-FDG) positron emission tomography (PET)/CT scan were retrospectively enrolled. Two treatment plans-one using DP escalation and one without-were optimized for each patient base on PET/CT data...
June 23, 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/28553585/dosimetric-and-radiobiological-evaluation-of-multiparametric-mri-guided-dose-painting-in-radiotherapy-of-prostate-cancer
#10
Iraj Abedi, Mohammad B Tavakkoli, Keyvan Jabbari, Alireza Amouheidari, Ghasem Yadegarfard
Radiotherapy is one of the treatment options for locally advanced prostate cancer; however, with standard radiation doses, it is not always very effective. One of the strategies to improve the efficiency of radiotherapy is increasing the dose. In this study, to increase tumor local control rates, a new radiotherapy method, known as dose painting (DP), was investigated. To compare 3-dimensional conformal radiotherapy (3D-CRT) and intensity modulated radiotherapy (IMRT) plans with DP for prostate cancer. Twenty-four consecutive patients with locally advanced prostate cancer who underwent an multiparametric-magnetic resonance imaging (MP-MRI) (T2w, diffusion weighted image, dynamic contrast enhancement, and MRS) scan before a diagnostic biopsy from September 2015 to April 2016 were invited to take part in this study...
April 2017: Journal of Medical Signals and Sensors
https://www.readbyqxmd.com/read/28550384/investigation-of-glycochenodeoxycholate-sulfate-and-chenodeoxycholate-glucuronide-as-surrogate-endogenous-probes-for-drug-interaction-studies-of-oatp1b1-and-oatp1b3-in-healthy-japanese-volunteers
#11
Issey Takehara, Hanano Terashima, Takeshi Nakayama, Takashi Yoshikado, Miwa Yoshida, Kenichi Furihata, Nobuaki Watanabe, Kazuya Maeda, Osamu Ando, Yuichi Sugiyama, Hiroyuki Kusuhara
PURPOSE: To assess the use of glycochenodeoxycholate-3-sulfate (GCDCA-S) and chenodeoxycholate 3- or 24-glucuronide (CDCA-3G or -24G) as surrogate endogenous substrates in the investigation of drug interactions involving OATP1B1 and OATP1B3. METHODS: Uptake of GCDCA-S and CDCA-24G was examined in HEK293 cells transfected with cDNA for OATP1B1, OATP1B3, and NTCP and in cryopreserved human hepatocytes. Plasma concentrations of bile acids and their metabolites (GCDCA-S, CDCA-3G, and CDCA-24G) were determined by LC-MS/MS in eight healthy volunteers with or without administration of rifampicin (600 mg, po)...
May 26, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28549616/pectin-penta-oligogalacturonide-reduces-cholesterol-accumulation-by-promoting-bile-acid-biosynthesis-and-excretion-in-high-cholesterol-fed-mice
#12
Ru-Gang Zhu, Yan-Di Sun, Yu-Ting Hou, Jun-Gang Fan, Gang Chen, Tuo-Ping Li
Haw pectin penta-oligogalacturonide (HPPS) has important role in improving cholesterol metabolism and promoting the conversion of cholesterol to bile acids (BA) in mice fed high-cholesterol diet (HCD). However, the mechanism is not clear. This study aims to investigate the effects of HPPS on cholesterol accumulation and the regulation of hepatic BA synthesis and transport in HCD-fed mice. Results showed that HPPS significantly decreased plasma and hepatic TC levels but increased plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) levels, compared to HCD...
June 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28543042/the-ntcp-inhibitor-myrcludex-b-effects-on-bile-acid-disposition-and-tenofovir-pharmacokinetics
#13
A Blank, A Eidam, M Haag, N Hohmann, J Burhenne, M Schwab, Sfj van de Graaf, M R Meyer, H H Maurer, K Meier, J Weiss, T Bruckner, A Alexandrov, S Urban, G Mikus, W E Haefeli
Myrcludex B acts as a hepatitis B and D virus entry inhibitor blocking the sodium taurocholate cotransporting polypeptide (SLC10A1). We investigated the effects of myrcludex B on plasma bile acid disposition, tenofovir pharmacokinetics, and perpetrator characteristics on cytochrome P450 (CYP) 3A. Twelve healthy volunteers received 300 mg tenofovir disoproxil fumarate orally and 10 mg subcutaneous myrcludex B. Myrcludex B increased total plasma bile acid exposure 19.2-fold without signs of cholestasis. The rise in conjugated bile acids was up to 124-fold (taurocholic acid)...
May 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28533986/atorvastatin-alters-the-expression-of-genes-related-to-bile-acid-metabolism-and-circadian-clock-in-livers-of-mice
#14
Wen-Kai Li, Huan Li, Yuan-Fu Lu, Ying-Ying Li, Zidong Donna Fu, Jie Liu
AIM: Atorvastatin is a HMG-CoA reductase inhibitor used for hyperlipidemia. Atorvastatin is generally safe but may induce cholestasis. The present study aimed to examine the effects of atorvastatin on hepatic gene expression related to bile acid metabolism and homeostasis, as well as the expression of circadian clock genes in livers of mice. METHODS: Adult male mice were given atorvastatin (10, 30, and 100 mg/kg, po) daily for 30 days, and blood biochemistry, histopathology, and gene expression were examined...
2017: PeerJ
https://www.readbyqxmd.com/read/28529062/quantitative-targeted-bile-acid-profiling-as-new-markers-for-dili-in-a-model-of-methapyrilene-induced-liver-injury-in-rats
#15
Markus Slopianka, Anne Herrmann, Mira Pavkovic, Heidrun Ellinger-Ziegelbauer, Rainer Ernst, Angela Mally, Matthias Keck, Bjoern Riefke
Recently, bile acids (BAs) were reported as promising markers for drug-induced liver injury (DILI). BAs have been suggested to correlate with hepatocellular and hepatobiliary damage; however a clear connection of BA patterns with different types of DILI remains to be established. To investigate if BAs can improve the assessment of liver injury, 20 specific BAs were quantitatively profiled via LC-MS/MS in plasma and liver tissue in a model of methapyrilene-induced liver injury in rats. Methapyrilene, a known hepatotoxin was dosed daily over 14-days at doses of 30 and 80mg/kg, followed by a recovery phase of 10days...
May 19, 2017: Toxicology
https://www.readbyqxmd.com/read/28506607/corrigendum-to-the-role-of-ntcp-oatp2-bsep-and-mrp2-in-liver-injury-induced-by-dioscorea-bulbifera-l-and-diosbulbin-b-in-mice-environ-toxicol-pharmacol-51-2017-16-22
#16
Xiao-Yu Qu, Li-Na Tao, Si-Xi Zhang, Jing-Meng Sun, Jun-Qi Niu, Yan-Hua Ding, Yan-Qing Song
No abstract text is available yet for this article.
May 12, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28506589/the-relationship-between-dosimetric-factors-side-effects-and-survival-in-patients-with-non-small-cell-lung-cancer-treated-with-definitive-radiotherapy
#17
Dilruba Okumus, Sureyya Sarihan, Sema Gozcu, Deniz Sigirli
The patients with non-small cell lung cancer (NSCLC) treated with definitive conformal radiotherapy (RT) were evaluated in terms of side effects and survival. Normal tissue complication probability (NTCP) was calculated for 68 patients treated between 2009 and 2012. Clinical and dosimetric factors were analyzed. The median dose of 63 Gy (range: 54 to 70 Gy) was given with conformal RT with blocks (n = 37), 3-dimensional conformal RT (3DCRT) (n = 11), or intensity-modulated RT (IMRT) (n = 20)...
May 12, 2017: Medical Dosimetry: Official Journal of the American Association of Medical Dosimetrists
https://www.readbyqxmd.com/read/28502238/parotid-gland-mean-dose-as-a-xerostomia-predictor-in-low-dose-domains
#18
Hubert Szymon Gabryś, Florian Buettner, Florian Sterzing, Henrik Hauswald, Mark Bangert
PURPOSE: Xerostomia is a common side effect of radiotherapy resulting from excessive irradiation of salivary glands. Typically, xerostomia is modeled by the mean dose-response characteristic of parotid glands and prevented by mean dose constraints to either contralateral or both parotid glands. The aim of this study was to investigate whether normal tissue complication probability (NTCP) models based on the mean radiation dose to parotid glands are suitable for the prediction of xerostomia in a highly conformal low-dose regime of modern intensity-modulated radiotherapy (IMRT) techniques...
May 13, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28499607/evaluation-of-intensity-modulated-radiation-therapy-dose-painting-for-localized-prostate-cancer-using-68-ga-hbed-cc-psma-pet-ct-a-planning-study-based-on-histopathology-reference
#19
Constantinos Zamboglou, Ilias Sachpazidis, Khodor Koubar, Vanessa Drendel, Rolf Wiehle, Simon Kirste, Michael Mix, Florian Schiller, Panayiotis Mavroidis, Philipp T Meyer, Martin Werner, Anca L Grosu, Dimos Baltas
PURPOSE: To demonstrate the feasibility and to evaluate the tumour control probability (TCP) and normal tissue complication probability (NTCP) of IMRT dose painting using (68)Ga-HBED-CC PSMA PET/CT for target delineation in prostate cancer (PCa). METHODS AND MATERIALS: 10 patients had PSMA PET/CT scans prior to prostatectomy. GTV-PET was generated on the basis of an intraprostatic SUVmax of 30%. Two IMRT plans were generated for each patient: Plan(77) which consisted of whole-prostate IMRT to 77Gy, and Plan(95) which consisted of whole-prostate IMRT to 77Gy and a simultaneous integrated boost to the GTV-PET up to 95Gy (35 fractions)...
May 9, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28498614/hepatic-uptake-of-conjugated-bile-acids-is-mediated-by-both-ntcp-and-oatps-and-modulated-by-intestinal-sensing-of-plasma-bile-acid-levels-in-mice
#20
Davor Slijepcevic, Reinout L P Roscam Abbing, Takeshi Katafuchi, Antje Blank, Joanne M Donkers, Stéphanie van Hoppe, Dirk R de Waart, Dagmar Tolenaars, Jonathan H M van der Meer, Manon Wildenberg, Ulrich Beuers, Ronald P J Oude Elferink, Alfred H Schinkel, Stan F J van de Graaf
BACKGROUND & AIMS: The Na(+) -taurocholate cotransporting polypeptide (NTCP/SLC10A1) is believed to be pivotal for hepatic uptake of conjugated bile acids. However, plasma bile acid levels are normal in a subset of NTCP knockout mice and in mice treated with myrcludex B, a specific NTCP inhibitor. Here, we elucidated which transport proteins mediate the hepatic uptake of conjugated bile acids and demonstrated intestinal sensing of elevated bile acid levels in plasma in mice. METHODS: Mice or healthy volunteers were treated with myrcludex B...
May 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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