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https://www.readbyqxmd.com/read/28639119/a-pharmacokinetic-drug-drug-interaction-study-between-selexipag-and-midazolam-a-cyp3a4-substrate-in-healthy-male-subjects
#1
Pierre-Eric Juif, Margaux Boehler, Yves Donazzolo, Shirin Bruderer, Jasper Dingemanse
PURPOSE: In vitro data showed that selexipag and its active metabolite (ACT-333679) have an inductive effect on CYP3A4, CYP2B6, and CYP2C9 at concentrations approximately 100-fold higher than the maximum plasma concentration (C max) measured under steady-state conditions. In order to confirm in vivo the lack of induction at the enterocyte level, we assessed the effect of selexipag on midazolam, a substrate of hepatic and intestinal CYP3A4. METHODS: This study was conducted according to an open-label, randomized, two-way crossover design...
June 21, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28633424/three-dimensional-3d-heparg-spheroid-model-with-physiologically-relevant-xenobiotic-metabolism-competence-and-hepatocyte-functionality-for-liver-toxicity-screening
#2
Sreenivasa C Ramaiahgari, Suramya Waidyanatha, Darlene Dixon, Michael J DeVito, Richard S Paules, Stephen S Ferguson
Effective prediction of human responses to chemical and drug exposure is of critical importance in environmental toxicology research and drug development. While significant progress has been made to address this challenge using in vitro liver models, these approaches often fail due to inadequate tissue model functionality. Herein, we describe the development, optimization, and characterization of a novel three-dimensional (3D) spheroid model using differentiated HepaRG cells that achieve and maintain physiologically-relevant levels of xenobiotic metabolism (CYP1A2, CYP2B6, and CYP3A4/5)...
June 15, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28631044/-personalized-treatment-of-viral-hepatitis-of-the-present-and-the-future-hepatitis%C3%A2-b-c-delta-and-e
#3
REVIEW
R Bartenschlager, M Cornberg, T Pietschmann
Precision medicine is also possible for infectious diseases as shown for the treatment of chronic viral hepatitis, especially if different options are available. In hepatitis B virus (HBV) infection, treatment indication as well as the choice of treatment and the decisions to stop treatment are based on viral markers and alanine aminotransferase (ALT) level. Future therapies for HBV infection aiming for functional cure or even virus elimination may be even more personalized and have to take into account the immune status of a given patient...
June 19, 2017: Der Internist
https://www.readbyqxmd.com/read/28627823/hepatitis-c-an-overview-of-various-laboratory-assays-with-their-mode-of-diagnostic-cooperation
#4
REVIEW
Mohammad-Ayman A Safi
BACKGROUND: This review describes in chronological order the different assays for hepatitis C virus (HCV) antibodies, for the core antigen and for the HCV-RNA. METHODS: By ascending chronological order, the enzyme-linked immunosorbent assay (ELISA), rapid diagnostic tests (RDTs), HCV-Ab IgG avidity index (HCV AI), and Cy3-labeled microarray assay have been described for HCV antibodies in addition to ELISA for the total HCV core antigen (Ag). RESULTS: The recombinant immunoblot assay (RIBA) is a confirmatory test for HCV-Ab in blood, which is no longer needed due to the use of the sensitive third and fourth generation ELISA in addition to HCV-RNA detection by the Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)...
May 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28627285/older-military-veteran-care-many-still-believe-they-are-forgotten
#5
Cathy Young, Patricia L Conard, Myrna L Armstrong, Darlene Lacy
BACKGROUND: Almost 44% of our nation's 23 million men and women veterans are 65 years of age or older. Most are proud of their service, yet many believe their services for our country were forgotten, especially those in combat between 1950 and 1975. PURPOSE: Further information to ultimately assist their holistic well-being will be important for nursing practice as countless older veterans are beginning to obtain more care within civilian facilities. Using the Korean War (1950-1953) as a backdrop to illustrate the interconnectiveness of older veteran physical, emotional, and spiritual concerns that can occur from a military deployment, the major purposes of this article are to provide a brief historical snapshot of that war and discuss prior-era military environmental situations that now are producing the lingering effects from their combat exposure...
June 1, 2017: Journal of Holistic Nursing: Official Journal of the American Holistic Nurses' Association
https://www.readbyqxmd.com/read/28620913/efficacy-of-oral-lipid-based-formulations-of-apomorphine-and-its-diester-in-a-parkinson-s-disease-rat-model
#6
Nrupa Borkar, Daniel R Andersson, Mingshi Yang, Anette Müllertz, René Holm, Huiling Mu
OBJECTIVES: Apomorphine is used to symptomatically treat Parkinson's disease (PD). Oral delivery of apomorphine is generally limited by its short plasma half-life and a hepatic first-pass metabolism. This study was aimed at evaluating the behavioural response of apomorphine and its prodrug administered in oral lipid-based formulations. METHODS: The behavioural response of apomorphine and its prodrug administered in oral lipid-based formulations was evaluated using a 6-hydroxydopamine-lesioned rat model simulating PD symptomatology...
June 16, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28611273/racial-disparities-in-hepatitis-c-treatment-eligibility
#7
Omar Sims, David Pollio, Barry Hong, Carol North
BACKGROUND: Hepatitis C (HCV) is more prevalent in African Americans than in any other racial group in the United States. However, African Americans are more likely to be deemed ineligible for HCV treatment than non-African Americans. There has been limited research into the origins of racial disparities in HCV treatment eligibility. AIM: The purpose of this study was to compare medical and non-medical characteristics commonly assessed in clinical practice that could potentially contribute to HCV treatment ineligibility disparities between African American and non-African American patients...
August 1, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28604703/cold-induced-conversion-of-cholesterol-to-bile-acids-in-mice-shapes-the-gut-microbiome-and-promotes-adaptive-thermogenesis
#8
Anna Worthmann, Clara John, Malte C Rühlemann, Miriam Baguhl, Femke-Anouska Heinsen, Nicola Schaltenberg, Markus Heine, Christian Schlein, Ioannis Evangelakos, Chieko Mineo, Markus Fischer, Maura Dandri, Claus Kremoser, Ludger Scheja, Andre Franke, Philip W Shaul, Joerg Heeren
Adaptive thermogenesis is an energy-demanding process that is mediated by cold-activated beige and brown adipocytes, and it entails increased uptake of carbohydrates, as well as lipoprotein-derived triglycerides and cholesterol, into these thermogenic cells. Here we report that cold exposure in mice triggers a metabolic program that orchestrates lipoprotein processing in brown adipose tissue (BAT) and hepatic conversion of cholesterol to bile acids via the alternative synthesis pathway. This process is dependent on hepatic induction of cytochrome P450, family 7, subfamily b, polypeptide 1 (CYP7B1) and results in increased plasma levels, as well as fecal excretion, of bile acids that is accompanied by distinct changes in gut microbiota and increased heat production...
June 12, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28598207/the-relationship-between-single-nucleotide-polymorphisms-the-expression-of-dna-damage-response-genes-and-hepatocellular-carcinoma-in-a-polish-population
#9
Renata Krupa, Piotr Czarny, Paulina Wigner, Joanna Wozny, Maciej Jablkowski, Radzislaw Kordek, Janusz Szemraj, Tomasz Sliwinski
The molecular mechanism of hepatocellular carcinoma (HCC) is related to DNA damage caused by oxidative stress products induced by hepatitis B virus (HBV) or C (HCV) infection and exposure to environmental pollutants. Single-nucleotide polymorphisms (SNPs) of DNA damage response (DDR) genes may influence individual susceptibility to environmental risk factors and affect DNA repair efficacy, which, in turn, can influence the risk of HCC. The study evaluates a panel of 15 SNPs in 11 DDR genes (XRCC1, XRCC3, XPD, MUTYH, LIG1, LIG3, hOGG1, PARP1, NFIL1, FEN1, and APEX1) in 65 HCC patients, 50 HBV- and 50 HCV-infected non-cancerous patients, and 50 healthy controls...
June 9, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28597609/transaminase-levels-and-hepatic-events-during-tocilizumab-treatment-pooled-analysis-of-long-term-clinical-trial-safety-data-in-rheumatoid-arthritis
#10
Mark C Genovese, Joel M Kremer, Ronald F van Vollenhoven, Rieke Alten, Juan Jose Scali, Ariella Kelman, Sophie Dimonaco, Laura Brockwell
OBJECTIVE: Investigate liver enzyme abnormalities and hepatic adverse events (AEs) during long-term tocilizumab treatment for rheumatoid arthritis (RA) in clinical trials. METHODS: Data were pooled from patients who received intravenous tocilizumab (4, 8, or 10 mg/kg ± disease-modifying antirheumatic drugs [DMARDs]) in phase 3 or 4 clinical trials, long-term extensions, and a pharmacology study. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured routinely in these trials...
June 8, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28597227/a-hemoglobin-adduct-as-a-biomarker-for-the-internal-exposure-to-the-rodent-carcinogen-furfuryl-alcohol
#11
Benjamin Sachse, Jan Hielscher, Alfonso Lampen, Klaus Abraham, Bernhard H Monien
Furfuryl alcohol is a common food contaminant, which is formed by acid- and heat-catalyzed degradation of fructose and glucose. Its carcinogenic effect in rodents originates most likely from sulfotransferase (SULT)-catalyzed conversion into the mutagenic sulfate ester 2-sulfoxymethylfuran. In this study, a protein adduct biomarker was sought for the medium-term internal exposure to furfuryl alcohol. A UPLC-MS/MS screening showed that the adduct N-((furan-2-yl)methyl)-Val (FFA-Val) at the N-terminus of hemoglobin is a valid target analyte...
June 8, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28595132/functionality-based-method-for-simultaneous-isolation-of-rodent-hepatic-sinusoidal-cells
#12
L Stradiot, S Verhulst, T Roosens, C I Øie, I M Moya, G Halder, I Mannaerts, L A van Grunsven
Chronic liver disease is the result of long term exposure to viruses or toxins such as alcohol, fat and drugs, and forms the basis for the development of liver fibrosis and primary liver cancer. In vitro and in vivo models are key to study the pathways involved in chronic liver disease and for the development of therapeutics. 3D co-culture systems are becoming the in vitro standard, which requires freshly isolated primary hepatic cells. We developed a novel isolation method to simultaneously isolate liver sinusoidal endothelial cells (LSECs), Kupffer cells (KCs) and hepatic stellate cells (HSCs)...
September 2017: Biomaterials
https://www.readbyqxmd.com/read/28592624/prolonged-pemetrexed-infusion-plus-gemcitabine-in-refractory-metastatic-colorectal-cancer-preclinical-rationale-and-phase-ii-study-results
#13
Alessandro Passardi, Francesca Fanini, Livia Turci, Flavia Foca, Paola Rosetti, Silvia Ruscelli, Andrea Casadei Gardini, Martina Valgiusti, Claudio Dazzi, Maurizio Marangolo
LESSONS LEARNED: Difficulties in translating in vitro results into clinical practice are inevitable.Further efforts to verify the efficacy of alternative schedules of pemetrexed in solid tumors are encouraged. BACKGROUND: We investigated the cytotoxic activity of pemetrexed in combination with several drugs (gemcitabine, carboplatin, vinorelbine, and mitomycin C) using different exposure schedules in three colon cancer cell lines. The best results were obtained with the following schedule: a prolonged pemetrexed exposure followed by a 48-hour wash-out and then gemcitabine...
June 7, 2017: Oncologist
https://www.readbyqxmd.com/read/28592092/-early-physical-growth-and-disease-analysis-among-children-born-delivered-by-hbsag-positive-mothers
#14
X H Zhang, Q Wang, W Zheng, X H Li, Q Q Jiang, C F Zhou, L Q Qiu
Objective: To estimate the early physical growth and disease in children born to HBsAg-positive mothers. Methods: This was a retrospective cohort study. Three areas as Xihu in Hangzhou, Lanxi in Jinhua, and Haiyan in Jiaxing in Zhejiang province were selected by cluster sampling. The growth outcomes of children born to HBsAg-positive mothers (exposure group) and matched 1∶1 women uninfected with HBV (control group) in 2014 were investigated and compared at birth, 6, 9, 12, and 18 months, respectively. There were totally 342 children in each group...
June 6, 2017: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/28589864/efficient-detection-of-viral-transmissions-with-next-generation-sequencing-data
#15
Inna Rytsareva, David S Campo, Yueli Zheng, Seth Sims, Sharma V Thankachan, Cansu Tetik, Jain Chirag, Sriram P Chockalingam, Amanda Sue, Srinivas Aluru, Yury Khudyakov
BACKGROUND: Hepatitis C is a major public health problem in the United States and worldwide. Outbreaks of hepatitis C virus (HCV) infections associated with unsafe injection practices, drug diversion, and other exposures to blood are difficult to detect and investigate. Molecular analysis has been frequently used in the study of HCV outbreaks and transmission chains; helping identify a cluster of sequences as linked by transmission if their genetic distances are below a previously defined threshold...
May 24, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28586700/injection-into-the-jugular-vein-among-people-who-inject-drugs-in-the-united-kingdom-prevalence-associated-factors-and-harms
#16
Vivian D Hope, Jenny Iversen, Katelyn J Cullen, John V Parry, Lisa Maher, Fortune Nucbe
BACKGROUND: While people who inject drugs (PWID) typically use peripheral veins, some inject into their central veins, including the femoral and jugular veins. Injection into the jugular vein can have serious adverse health consequences, including jugular vein thrombosis, deep neck infections, pneumothorax, endocarditis and sepsis. This study examined the prevalence of, and factors associated with, jugular vein injection among a large sample of PWID in the United Kingdom. METHOD: Unlinked anonymous surveys (2011-14) recruited PWID from agencies providing services to this population...
June 3, 2017: International Journal on Drug Policy
https://www.readbyqxmd.com/read/28585748/effects-of-curcumin-on-tobacco-smoke-induced-hepatic-mapk-pathway-activation-and-epithelial-mesenchymal-transition-in-vivo
#17
Zhaofeng Liang, Rui Wu, Wei Xie, Chunfeng Xie, Jieshu Wu, Shanshan Geng, Xiaoting Li, Mingming Zhu, Weiwei Zhu, Jianyun Zhu, Cong Huang, Xiao Ma, Wenrong Xu, Caiyun Zhong, Hongyu Han
Tobacco smoke is a major risk factor for hepatic cancer. Epithelial-mesenchymal transition (EMT) induced by tobacco smoke is crucially involved in the initiation and development of cancer. Mitogen-activated protein kinase (MAPK) pathways play important roles in tobacco smoke-associated carcinogenesis including EMT process. The chemopreventive effect of curcumin supplementation against cancers has been reported. In this study, we investigated the effects of tobacco smoke on MAPK pathway activation and EMT alterations, and then the preventive effect of curcumin was examined in the liver of BALB/c mice...
June 6, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28584337/-hbv-hcv-and-hiv-infection-prevalence-among-prison-staff-in-the-light-of-occupational-risk-factors
#18
Maria Gańczak, Zbigniew Szych
BACKGROUND: Objectives of the study: to assess the occupational risk for blood-borne infections (BBIs) among prison staff (number/ circumstances of blood exposures and preventive methods used), and to estimate the prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). MATERIAL AND METHODS: The survey, which included serological testing with the use of 3-generation enzyme-linked immunosorbent assays (ELISA) was completed on active staff at a correctional facility in Goleniów, Poland, between June-July 2015...
May 15, 2017: Medycyna Pracy
https://www.readbyqxmd.com/read/28577690/value-of-comprehensive-hcv-treatment-among-vulnerable-high-risk-populations
#19
Gigi A Moreno, Alice Wang, Yuri Sánchez González, Oliver Díaz Espinosa, Diana K Vania, Brian R Edlin, Ronald Brookmeyer
OBJECTIVES: The objective of this study was to explore the trade-offs society and payers make when expanding treatment access to patients with chronic hepatitis C virus (HCV) infection in early stages of disease as well as to vulnerable, high-risk populations, such as people who inject drugs (PWID) and HIV-infected men who have sex with men (MSM-HIV). METHODS: A discrete time Markov model simulated HCV progression and treatment over 20 years. Population cohorts were defined by behaviors that influence the risk of HCV exposure: PWID, MSM-HIV, an overlap cohort of individuals who are both PWID and MSM-HIV, and all other adults...
June 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/28577129/effects-of-mild-to-severe-hepatic-impairment-on-the-pharmacokinetics-of-sonidegib-a-multicenter-open-label-parallel-group-study
#20
Yves Horsmans, Jocelyn Zhou, Mateva Liudmila, George Golor, Oren Shibolet, Michelle Quinlan, Corinne Emotte, Hildegard Boss, Henry Castro, Dalila Sellami, Richard A Preston
BACKGROUND AND OBJECTIVE: Sonidegib is a potent, selective and orally bioavailable inhibitor of the Hedgehog signaling pathway, primarily metabolized by the liver. In order to make dose recommendations for patients with hepatic impairment, we have assessed here the pharmacokinetics (PKs) and safety of sonidegib in subjects with varying degrees of hepatic function. METHODS: The primary objective of this phase I, multicenter, open-label study was to evaluate the PKs of a single oral 800 mg dose of sonidegib in subjects with impaired hepatic function compared with healthy subjects...
June 2, 2017: Clinical Pharmacokinetics
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