5,397,912 results match your criteria Drug Metabolism and Drug Interactions[Journal]

  • Page 1 of 107959

[Quality of life as a target criterion in schizophrenia therapy].

Fortschr Neurol Psychiatr 2018 Dec 12. Epub 2018 Dec 12.

Praxis Dr. Wietfeld, Fachärztin für Neurologie, Psychiatrie und Psychotherapie.

Consideration of quality of life has developed into an important concept of a patient-oriented medicine in the last 50 years. With it, it should be possible to capture the subjective experience of the patients and describe its different dimensions. Today, the quality of life as a patient-reported endpoint is also an integral part of the early benefit assessment under the German Drug Market Reorganization Act. Read More

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December 2018
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Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs.

Nucleic Acids Res 2018 Dec 12. Epub 2018 Dec 12.

Department of Chemistry, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.

Transfer RNA is heavily modified and plays a central role in protein synthesis and cellular functions. Here we demonstrate that ALKBH3 is a 1-methyladenosine (m1A) and 3-methylcytidine (m3C) demethylase of tRNA. ALKBH3 can promote cancer cell proliferation, migration and invasion. Read More

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December 2018

Assessment of drug interaction potential between the HCV direct-acting antiviral agents elbasvir/grazoprevir and the HIV integrase inhibitors raltegravir and dolutegravir.

J Antimicrob Chemother 2018 Dec 12. Epub 2018 Dec 12.

Merck & Co., Inc., Kenilworth, USA.

Background: Elbasvir/grazoprevir is a once-daily fixed-dose combination therapy for the treatment of chronic HCV infection, including HCV/HIV coinfection.

Objectives: To evaluate the pharmacokinetic interaction of elbasvir and grazoprevir with raltegravir or dolutegravir.

Methods: Three open-label trials in healthy adult participants were conducted. Read More

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December 2018
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Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer.

Authors:
Naomi Walsh Han Zhang Paula L Hyland Qi Yang Evelina Mocci Mingfeng Zhang Erica J Childs Irene Collins Zhaoming Wang Alan A Arslan Laura Beane-Freeman Paige M Bracci Paul Brennan Federico Canzian Eric J Duell Steven Gallinger Graham G Giles Michael Goggins Gary E Goodman Phyllis J Goodman Rayjean J Hung Charles Kooperberg Robert C Kurtz Núria Malats Loic LeMarchand Rachel E Neale Sara H Olson Ghislaine Scelo Xiao O Shu Stephen K Van Den Eeden Kala Visvanathan Emily White Wei Zheng Demetrius Albanes Gabriella Andreotti Ana Babic William R Bamlet Sonja I Berndt Ayelet Borgida Marie-Christine Boutron-Ruault Lauren Brais Paul Brennan Bas Bueno-de-Mesquita Julie Buring Kari G Chaffee Stephen Chanock Sean Cleary Michelle Cotterchio Lenka Foretova Charles Fuchs J Michael M Gaziano Edward Giovannucci Michael Goggins Thilo Hackert Christopher Haiman Patricia Hartge Manal Hasan Kathy J Helzlsouer Joseph Herman Ivana Holcatova Elizabeth A Holly Robert Hoover Rayjean J Hung Vladimir Janout Eric A Klein Robert C Kurtz Daniel Laheru I-Min Lee Lingeng Lu Núria Malats Satu Mannisto Roger L Milne Ann L Oberg Irene Orlow Alpa V Patel Ulrike Peters Miquel Porta Francisco X Real Nathaniel Rothman Howard D Sesso Gianluca Severi Debra Silverman Oliver Strobel Malin Sund Mark D Thornquist Geoffrey S Tobias Jean Wactawski-Wende Nick Wareham Elisabete Weiderpass Nicolas Wentzensen William Wheeler Herbert Yu Anne Zeleniuch-Jacquotte Peter Kraft Donghui Li Eric J Jacobs Gloria M Petersen Brian M Wolpin Harvey A Risch Laufey T Amundadottir Kai Yu Alison P Klein Rachael Z Stolzenberg-Solomon

J Natl Cancer Inst 2018 Dec 12. Epub 2018 Dec 12.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.

Background: Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes.

Methods: We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. Read More

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December 2018

Predicting Ames Mutagenicity Using Conformal Prediction in the Ames/QSAR International Challenge Project.

Mutagenesis 2018 Dec 12. Epub 2018 Dec 12.

Computer Learning Research Centre, Royal Holloway, University of London Egham, Surrey, UK.

Valid and predictive models for classifying Ames mutagenicity have been developed using conformal prediction. The models are Random Forest models using signature molecular descriptors. The investigation indicates, on excluding not-strongly mutagenic compounds (class B), that the validity for mutagenic compounds is increased for the predictions based on both public and the Division of Genetics and Mutagenesis, National Institute of Health Sciences of Japan (DGM/NIHS) data while less so when using only the latter data source. Read More

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December 2018

CD33 in Alzheimer's Disease - Biology, Pathogenesis, and Therapeutics: A Mini-Review.

Authors:
Lingzhi Zhao

Gerontology 2018 Dec 12:1-9. Epub 2018 Dec 12.

Alzheimer's disease (AD) affects nearly 50 million people worldwide, and currently no disease-modifying treatment is available. With continuous failure of anti-amyloid-beta- or tau-based therapies, identification of new targets has become an urgent necessity for AD prevention and therapy. Recently, conventional genetic approaches and computational strategies have converged on immune-inflammatory pathways as key events in the pathogenesis of AD. Read More

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December 2018
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Antidiarrheal activity of α-terpineol in mice.

Biomed Pharmacother 2018 Dec 8;110:631-640. Epub 2018 Dec 8.

Medicinal Plants Research Center (NPPM), Federal University of Piauí, 64.049-550, Teresina, PI, Brazil. Electronic address:

Diarrhea is one of the leading causes of infant death in the world accounting for high child mortality rate. It is also present in different pathophysiologies related to several etiological agents. The aim of this study is to investigate the antidiarrheal effect of α -Terpineol (α-TPN) in different diarrhea models in rodents. Read More

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December 2018

Photothermally controlled drug release system with high dose loading for synergistic chemo-photothermal therapy of multidrug resistance cancer.

Colloids Surf B Biointerfaces 2018 Dec 5;175:239-247. Epub 2018 Dec 5.

Laboratory of Environmental Sciences and Technology, Xinjiang Technical Institute of Physics & Chemistry, Chinese Academy of Sciences, Urumqi, Xinjiang 830011, China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, China. Electronic address:

Chemotherapy is an important first-line strategy for tumor therapy in cancer treatment, but multidrug resistance (MDR) is a major problem that reduces the efficacy of chemotherapeutics. Herein, we report a novel photothermally controlled intelligent drug release system (AuNP@mSiO-DOX-FA) with a large amount of drugs loading for synergistic chemo-photothermal therapy of MDR in breast cancer. The nanoplatform utilized gold nanoparticles as a hyperthermia core, and large-mesoporous silica as a shell for doxorubicin (DOX) loading. Read More

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December 2018

Development of a Human iPSC Cardiomyocyte-Based Scoring System for Cardiac Hazard Identification in Early Drug Safety De-risking.

Stem Cell Reports 2018 Dec;11(6):1365-1377

Global Safety Pharmacology, Non-Clinical Safety, Janssen Research & Development, A Division of Janssen Pharmaceutica NV, Turnhoutseweg 30, 2340 Beerse, Belgium.

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising cardiac safety platform, demonstrated by numerous validation studies using drugs with known cardiac adverse effects in humans. However, the challenge remains to implement hiPSC-CMs into cardiac de-risking of new chemical entities (NCEs) during preclinical drug development. Here, we used the calcium transient screening assay in hiPSC-CMs to develop a hazard score system for cardiac electrical liabilities. Read More

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December 2018

Screening-Based Chemical Approaches to Unravel Stem Cell Biology.

Authors:
Shuibing Chen

Stem Cell Reports 2018 Dec;11(6):1312-1323

Department of Surgery and Biochemistry, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA. Electronic address:

Cell-permeable compounds provide a convenient and efficient approach to manipulate biological processes. A number of compounds controlling stem cell self-renewal, survival, differentiation, and reprogramming have been identified through high-throughput/content screens. Using these powerful chemical tools, strategies have been developed to direct human pluripotent stem cell (hPSC) differentiation to functional cells. Read More

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December 2018

Dual Inhibition of the Lactate Transporters MCT1 and MCT4 Is Synthetic Lethal with Metformin due to NAD+ Depletion in Cancer Cells.

Cell Rep 2018 Dec;25(11):3047-3058.e4

Biozentrum, University of Basel, 4056 Basel, Switzerland. Electronic address:

Highly glycolytic cancer cells prevent intracellular acidification by excreting the glycolytic end-products lactate and H via the monocarboxylate transporters 1 (MCT1) and 4 (MCT4). We report that syrosingopine, an anti-hypertensive drug, is a dual MCT1 and MCT4 inhibitor (with 60-fold higher potency on MCT4) that prevents lactate and H efflux. Syrosingopine elicits synthetic lethality with metformin, an inhibitor of mitochondrial NADH dehydrogenase. Read More

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December 2018

Myeloid-Derived Suppressor Cells Produce IL-10 to Elicit DNMT3b-Dependent IRF8 Silencing to Promote Colitis-Associated Colon Tumorigenesis.

Cell Rep 2018 Dec;25(11):3036-3046.e6

Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USA; Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA; Charlie Norwood VA Medical Center, Augusta, GA 30904, USA. Electronic address:

IL-10 functions as a suppressor of colitis and colitis-associated colon cancer, but it is also a risk locus associated with ulcerative colitis. The mechanism underlying the contrasting roles of IL-10 in inflammation and colon cancer is unknown. We report here that inflammation induces the accumulation of CD11bGr1 myeloid-derived suppressor cells (MDSCs) that express high levels of IL-10 in colon tissue. Read More

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December 2018

Novel therapeutic approaches in primary hyperoxaluria.

Expert Opin Emerg Drugs 2018 Dec 12:1-9. Epub 2018 Dec 12.

a Division of Pediatric Nephrology , University Childrens Hospital, Universitatsklinikum Bonn , Bonn , Germany.

Introduction: Currently, three types of primary hyperoxaluria (PH I-III) are known, all based on different gene-mutations affecting the glyoxylate metabolism in the liver. Disease hallmark is an increased endogenous oxalate production and thus massively elevated urinary excretion of oxalate and other type-specific metabolites. Hyperoxaluria induces the formation of calcium-oxalate kidney stones and/or nephrocalcinosis. Read More

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December 2018

Biphenyl Gal and GalNAc FmlH Lectin Antagonists of Uropathogenic E. coli (UPEC): Optimization through iterative rational drug design.

J Med Chem 2018 Dec 12. Epub 2018 Dec 12.

The F9/Yde/Fml pilus, tipped with the FmlH adhesin, has been shown to provide Uropathogenic Escherichia coli (UPEC) a fitness advantage in urinary tract infections (UTIs). Here, we used X-ray structure guided design to optimize our previously described ortho-biphenyl Gal and GalNAc FmlH antagonists such as compound 1, by replacing the carboxylate with a sulfonamide as in 50. Other groups which can accept H-bonds were also tolerated. Read More

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December 2018

Orphan Receptor GPR88 as an Emerging Neurotherapeutic Target.

ACS Chem Neurosci 2018 Dec 12. Epub 2018 Dec 12.

While G protein-coupled receptors (GPCRs) are recognized as pivotal drug targets involved in multiple physiological and pathological processes, the majority of GPCRs including orphan GPCRs (oGPCRs) are unexploited. GPR88, a brain-specific oGPCR with particularly robust expression in the striatum, regulates diverse brain and behavioral functions including cognition, mood, movement control and reward-based learning, and is thus emerging as a novel drug target for CNS disorders including schizophrenia, Parkinson's disease, anxiety and addiction. Nevertheless, no effective GPR88 synthetic ligands have yet entered into clinical trials and GPR88 endogenous ligands remain unknown. Read More

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December 2018

Exploring the influence from whole blood DNA extraction methods on Infinium 450K DNA methylation.

PLoS One 2018 12;13(12):e0208699. Epub 2018 Dec 12.

Department of Pediatric Oncology and Hematology, Oslo University Hospital, Oslo, Norway.

Genome-wide DNA methylation studies are becoming increasingly important in unraveling the epigenetic basis of cell biology, aging and human conditions. The aim of the present study was to explore whether different methods for extracting DNA from whole blood can affect DNA methylation outcome, potentially confounding DNA methylation studies. DNA was isolated from healthy blood donors (n = 10) using three different extraction methods (i. Read More

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December 2018

Evaluating the impact of meloxicam oral suspension administered at parturition on subsequent production, health, and culling in dairy cows: A randomized clinical field trial.

PLoS One 2018 12;13(12):e0209236. Epub 2018 Dec 12.

Solvet Animal Health, Calgary, Alberta, Canada.

Parturition is a painful event experienced by cows at the onset of lactation. This pain could lead to a reduced feed intake, altered metabolic and immunological status, and a host of other diseases that could seriously limit her productive herd lifespan. The objective of the current study was to assess the effect of administration of a single dose of oral meloxicam, a non-steroidal anti-inflammatory drug (NSAID), on the production and health status of cows during their lactation. Read More

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December 2018

Dietary total antioxidant capacity (TAC) among candidates for coronary artery bypass grafting (CABG) surgery: Emphasis to possible beneficial role of TAC on serum vitamin D.

PLoS One 2018 12;13(12):e0208806. Epub 2018 Dec 12.

Department of Research, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Aims: Recently, the clinical importance of total antioxidant capacity (TAC) and its protective role against several chronic diseases like cardiovascular disease, osteoporosis and several types of cancers has been reported. However, its association with cardio-metabolic risk factors among patients candidate for coronary artery bypass graft surgery (CABG) has not been evaluated yet. CABG is associated with increased oxidative stress and free radicals; so, the current study was aimed to evaluate the potential association of TAC with cardiovascular risk factors among patients candidate for CABG. Read More

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December 2018
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Penetration of new antidiabetic medications in East Asian countries and the United States: A cross-national comparative study.

PLoS One 2018 12;13(12):e0208796. Epub 2018 Dec 12.

Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, United States of America.

Background: The number of patients with diabetes is increasing particularly in Asia-Pacific region. Many of them are treated with antidiabetics. As the basis of the studies on the benefit and harm of antidiabetic drugs in the region, the information on patterns of market penetration of new classes of antidiabetic medications is important in providing context for subsequent research and analyzing and interpreting results. Read More

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December 2018

Corticosteroid use and increased CXCR2 levels on leukocytes are associated with lumacaftor/ivacaftor discontinuation in cystic fibrosis patients homozygous for the F508del CFTR mutation.

PLoS One 2018 12;13(12):e0209026. Epub 2018 Dec 12.

Department of Pediatrics, National Jewish Health, Denver, CO, United States of America.

Cystic fibrosis (CF) is the most common life-shortening genetic disease and is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Several current therapies aim at improving availability and/or function of the mutant CFTR proteins. The combination therapeutic lumacaftor/ivacaftor (Orkambi, luma/iva) partially corrects folding and potentiates CFTR function impaired by the F508del mutation. Read More

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December 2018

Chitosan-based nanodelivery systems applied to the development of novel triclabendazole formulations.

PLoS One 2018 12;13(12):e0207625. Epub 2018 Dec 12.

Institute of Plant Biology and Biotechnology (IBBP), Westfälische Wilhelms-Universität Münster, Münster, Germany.

Triclabendazole is a poorly-water soluble (0.24 μg/mL) compound classified into the Class II/IV of the Biopharmaceutical Classification System. It is the drug of choice to treat fascioliasis, a neglected parasitic disease worldwide disseminated. Read More

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December 2018
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Antimicrobial resistance, plasmid, virulence, multilocus sequence typing and pulsed-field gel electrophoresis profiles of Salmonella enterica serovar Typhimurium clinical and environmental isolates from India.

PLoS One 2018 12;13(12):e0207954. Epub 2018 Dec 12.

Division of Bacteriology, Indian Council of Medical Research-National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a common serovar associated with non-typhoidal salmonellosis globally. However, there is insufficient data on molecular characterization of S. Read More

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December 2018

Chronic lifestyle diseases display seasonal sensitive comorbid trend in human population evidence from Google Trends.

PLoS One 2018 12;13(12):e0207359. Epub 2018 Dec 12.

Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Timarpur, Delhi, India.

Seasonal and human physiological changes are important factors in the development of many diseases. But, the study of genuine seasonal impact on these diseases is difficult to measure due to many other environment and lifestyle factors which directly affect these diseases. However, several clinical studies have been conducted in different parts of the world, and it has clearly indicated that certain groups of population are highly subjected to seasonal changes, and their maladaptation can possibly lead to several disorders/diseases. Read More

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December 2018

Antibiotic prescribing practices in secondary and tertiary hospitals in Shaanxi province, western China, 2013-2015.

PLoS One 2018 12;13(12):e0207229. Epub 2018 Dec 12.

Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.

Introduction: The irrational use of antibiotics is a major driver of antimicrobial resistance. This study aimed to explore how antibiotics were used in secondary and tertiary hospitals in Shaanxi Province, western China from 2013 to 2015.

Method: A retrospective study was conducted with a sample of 16 hospitals in Shaanxi Province (2 tertiary and 14 secondary hospitals; 8 public and 8 private hospitals) using a stratified random sampling method. Read More

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December 2018

Screen for modulators of atonal homolog 1 gene expression using notch pathway-relevant gene transcription based cellular assays.

PLoS One 2018 12;13(12):e0207140. Epub 2018 Dec 12.

R&D Alternative Discovery and Development, GlaxoSmithKline, Stevenage, Hertfordshire, United Kingdom.

Atonal homolog 1 (Atoh1) is a basic helix-loop-helix 9 (bHLH) transcription factor acting downstream of Notch and is required for the differentiation of sensory hair cells in the inner ear and the specification of secretory cells during the intestinal crypt cell regeneration. Motivated by the observations that the upregulation of Atoh1 gene expression, through genetic manipulation or pharmacological inhibition of Notch signaling (e.g. Read More

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December 2018

Antiemetic Drug Use in Children: What the Clinician Needs to Know.

J Pediatr Gastroenterol Nutr 2018 Dec 11. Epub 2018 Dec 11.

Clinical Pharmacology & Digestive Pathophysiology Unit, Department of Clinical & Experimental Medicine, University of Parma, Parma, Italy.

Vomiting is not only unpleasant for both children and families, but can lead to frequent hospital admission. The persistent vomiting hampers oral intake and increases the risk of dehydration so the proper use of antiemetic drugs can be useful. The pharmacological treatment of vomiting in children remains a challenge for the pediatrician because several antiemetics are prescribed as "off-label", outside their authorized drug label. Read More

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December 2018

A Novel Research Method for Determining Sedative Exposure in Critically Ill Patients.

Nurs Res 2019 Jan/Feb;68(1):73-79

Mary Fran Tracy, PhD, RN, APRN, CNS, FAAN, is Associate Professor, University of Minnesota School of Nursing, and Nurse Scientist, University of Minnesota Medical Center, Minneapolis. Linda Chlan, PhD, RN, ATSF, FAAN, is Associate Dean for Nursing Research and Professor of Nursing, Mayo Clinic College of Medicine and Science, Rochester, Minnesota. Kay Savik, MS, is Senior Statistician, University of Minnesota School of Nursing, Minneapolis. Debra J. Skaar, PharmD, FCCM, is Associate Professor of Experimental & Clinical Pharmacology, University of Minnesota College of Pharmacy, Minneapolis. Craig Weinert, MD, MPH, is Professor of Medicine, Pulmonary, Allergy, Critical Care, and Sleep Medicine Division, University of Minnesota Medical School, Minneapolis.

Background: Although potent sedative and opioid drugs are some of the most commonly used medications to manage pain, anxiety, and discomfort in critically ill patients, conducting clinical trials where sedative and opioid medications are outcome variables within a longitudinal research design can be a methodological challenge.

Objectives: The purpose of this article is to provide in detail a conceptual discussion of the concept and analysis of sedative exposure: A novel research analysis method for aggregating sedative and opioid medication doses from disparate drug classes commonly administered to critically ill patients and used by our team in several clinical research studies.

Methods: Comparing the dose of each sedative and opioid administered to an individual patient (within a defined time interval) to all other patients in a research study receiving the same medications allows for ranking of dosages for each medication by quartiles. Read More

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December 2018

Atorvastatin improves doxorubicin-induced cardiac dysfunction by modulating Hsp70, Akt and MAPK signalling pathways.

J Cardiovasc Pharmacol 2018 Dec 10. Epub 2018 Dec 10.

Department of Cardiology, The Second Hospital of Shandong University, Jinan, China.

Atorvastatin is a lipid-regulating drug that is commonly used in clinical practice and can stabilize plaques. Increasing evidence shows that statins have anti-heart failure effects, but their specific mechanism is not clear. The purpose of this study was to investigate the cardioprotective effects of atorvastatin on heart failure in rats and its mechanism. Read More

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December 2018
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Sacubitril/valsartan in daily clinical practice: data from a prospective registry.

J Cardiovasc Pharmacol 2018 Dec 10. Epub 2018 Dec 10.

Servicio de Cardiología. Hospital Universitario Gregorio Marañón. CIBERCV. Madrid, Spain.

Sacubitril/valsartan (SV) is a new therapy in heart failure with reduced ejection fraction. Our aim was to determine the efficacy and safety of this drug daily clinical practice.We performed a multicenter registry in 10 hospitals. Read More

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December 2018
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Population pharmacokinetic analysis of bisoprolol in patients with acute coronary syndrome.

J Cardiovasc Pharmacol 2018 Dec 10. Epub 2018 Dec 10.

Department of Pharmacology and Toxicology, Faculty of Medicine, University of Niš, Serbia.

To date, many questions about the extent and cause of pharmacokinetic variability of even the most widely studied and prescribed β1-adrenergic receptor blockers, such as metoprolol and bisoprolol, remain unanswered. Given that there are still no published population pharmacokinetic (PopPK) analyses of bisoprolol in routinely treated patients with acute coronary syndrome (ACS), the aim of this study was to determine its PK variability in 71 Serbian patients with ACS. PopPK analysis was carried out using a non-linear mixed effects model (NONMEM), version 7. Read More

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December 2018

Substantial differences in serum concentrations of psychoactive drugs measured in samples stored for two days or more on standard serum tubes versus serum tubes containing gel separators.

Ther Drug Monit 2018 Dec 11. Epub 2018 Dec 11.

Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.

Background: Drugs may potentially adsorb to blood collection tubes containing gel separators in the pre-analytical phase of therapeutic drug monitoring (TDM). The aim of this study was to compare measured concentrations of 28 psychoactive drugs and 13 metabolites in spiked serum samples stored on standard (plain) tubes vs. barrier gel tubes during a 2-6 days period at room temperature. Read More

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December 2018

Effects of vasodilating medications on cerebral haemodynamics in health and disease: systematic review and meta-analysis.

J Hypertens 2018 Dec 11. Epub 2018 Dec 11.

Centre for Prevention of Stroke and Dementia, John Radcliffe Hospital, University of Oxford, Oxford, UK.

Objectives: Vasodilating antihypertensives prevent stroke and potentially cerebral small vessel disease but their effects on cerebrovascular haemodynamics beyond blood pressure lowering are unclear.

Methods: We searched PubMed, Medline, Embase, Cinahl, Psychinfo, Health Business Elite and Health Management Information Consortium for randomized studies of vasodilating medications, compared to no treatment or nonvasodilators, that reported effects on cerebral blood flow (CBF), mean blood flow velocity (MFV) or cerebrovascular reactivity. Absolute and standardized mean differences (SMD) were combined by inverse-variance weighted fixed or random-effects meta-analysis stratified by study design, population characteristics and vasodilator class. Read More

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December 2018
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Hemodynamic effects of the dipeptidyl peptidase-4 inhibitor linagliptin with renin-angiotensin system inhibitors in type 2 diabetic patients with albuminuria.

J Hypertens 2018 Dec 11. Epub 2018 Dec 11.

Boehringer Ingelheim International GmbH, Ingelheim.

Objective: Concomitant treatment with angiotensin-converting enzyme (ACE) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors is increasingly common. Pharmacological studies have suggested a potential adverse drug interaction between ACE inhibitors and DPP-4 inhibitors resulting in unfavorable hemodynamic changes; very few studies have examined such an interaction between angiotensin II receptor blockers (ARBs) and DPP-4 inhibitors. We investigated blood pressure (BP) and heart rate (HR) during treatment with the DPP-4 inhibitor linagliptin in individuals receiving either ACE inhibitors or ARBs in the MARLINA-T2D trial. Read More

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December 2018

Design and rationale of the Edoxaban Treatment in routiNe clinical prActice for patients with Atrial Fibrillation in Europe (ETNA-AF-Europe) study.

J Cardiovasc Med (Hagerstown) 2018 Dec 11. Epub 2018 Dec 11.

Institute of Cardiovascular Sciences, University of Birmingham, SWBH and UHB NHS Trusts, Birmingham, UK.

Aim: Edoxaban, a nonvitamin K antagonist oral anticoagulant, is an oral factor Xa inhibitor approved for the prevention of stroke and systemic embolism in adult patients with atrial fibrillation and for the treatment and secondary prevention in adult patients with venous thromboembolism (VTE). This study details the design of the Edoxaban Treatment in routiNe clinical prActice for patients with Atrial Fibrillation in Europe (ETNA-AF-Europe) study - a postauthorization observational study, which is part of the postapproval plan for edoxaban agreed with the European Medicines Agency.

Methods: The ETNA-AF-Europe study (Clinicaltrials. Read More

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December 2018
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Artemisinin and its derivatives: a potential treatment for leukemia.

Anticancer Drugs 2019 Jan;30(1):1-18

Department of Pathology.

Artemisinin (ART) and its derivatives are one of the most important classes of antimalarial agents, originally derived from a Chinese medicinal plant called Artemisia annua L. Beyond their outstanding antimalarial and antischistosomal activities, ART and its derivatives also possess both in-vitro and in-vivo activities against various types of cancer. Their anticancer effects range from initiation of apoptotic cell death to inhibition of cancer proliferation, metastasis and angiogenesis, and even modulation of the cell signal transduction pathway. Read More

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January 2019
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Cabergoline in the Management of Residual Nonfunctioning Pituitary Adenoma: A Single-Center, Open-Label, 2-Year Randomized Clinical Trial.

Am J Clin Oncol 2018 Dec 11. Epub 2018 Dec 11.

Division of Functional Neurosurgery, Institute of Psychiatry-IPq, Hospital das Clinicas, FMUSP.

Background: Complete tumor removal by transsphenoidal surgery is usually difficult for large nonfunctioning pituitary adenomas (NFPAs). A validated medical treatment may be useful for their management. This study evaluates the clinical efficacy of the dopaminergic agonist cabergoline for residual NFPA. Read More

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December 2018

Amelioration of amyloid β-FcγRIIb neurotoxicity and tau pathologies by targeting LYN.

FASEB J 2018 Dec 12:fj201800926R. Epub 2018 Dec 12.

School of Biological Sciences, Seoul National University, Seoul, South Korea; and.

SRC-family kinases (SFKs) have been implicated in Alzheimer's disease (AD), but their mode of action was scarcely understood. Here, we show that LYN plays an essential role in amyloid β (Aβ)-triggered neurotoxicity and tau hyperphosphorylation by phosphorylating Fcγ receptor IIb2 (FcγRIIb2). We found that enzyme activity of LYN was increased in the brain of AD patients and was promoted in neuronal cells exposed to Aβ 1-42 (Aβ). Read More

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December 2018
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Active Targeting of Cancer Cells by Nanobody Decorated Polypeptide Micelle with Bioorthogonally Conjugated Drug.

Nano Lett 2018 Dec 12. Epub 2018 Dec 12.

Polypeptides are exceptionally promising carriers for chemotherapeutics: they have minimal toxicity, can be recombinantly synthesized with precise control over molecular weight, and enhance drug pharmacokinetics as self-assembled nanoparticles. Polypeptide-based systems also provide the ability to achieve active targeting with genetically encoded targeting ligands. While passive targeting promotes accumulation of nanocarriers in solid tumors, active targeting provides an additional layer of tunable control and widens the therapeutic window. Read More

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December 2018
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Engineered 3D microvascular networks for the study of ultrasound-microbubble-mediated drug delivery.

Langmuir 2018 Dec 12. Epub 2018 Dec 12.

Localized and targeted drug delivery can be achieved by the combined action of ultrasound, and microbubbles on the tumor microenvironment, likely through sonoporation and other therapeutic mechanisms not well understood. Here, we present a perfusable in vitro model with a realistic 3D geometry to study the interactions between microbubbles and the vascular endothelium in the presence of ultrasound. Specifically, a three-dimensional, endothelial-cell-seeded in vitro microvascular model was perfused with cell culture medium and microbubbles while sonicated by a single-element 1 MHz focused transducer. Read More

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December 2018
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