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drugs testing and analysis

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https://www.readbyqxmd.com/read/29778019/phoenix-dactylifera-protects-against-oxidative-stress-and-hepatic-injury-induced-by-paracetamol-intoxication-in-rats
#1
Gamal A Salem, Ahmed Shaban, Hussain A Diab, Wesam A Elsaghayer, Manal D Mjedib, Aomassad M Hnesh, Ravi P Sahu
The current studies were sought to determine effects of antioxidant potential of aqueous and methanolic extracts of Phoenix dactylifera leaves (PLAE and PLME) against the widely-used analgesic paracetamol (PCM) induced hepatotoxicity. Groups of rats were treated with or without PCM (1500 mg/kg), PLAE and PLME (300 mg/kg) and n-acetylcysteine (NAC, 50 mg/kg) followed by assessments of liver function tests, oxidative stress, antioxidant defenses, and hepatotoxicity. We observed that PCM significantly elevated serum liver markers, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and bilirubin compared to control (untreated) group...
May 16, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29778010/exposure-to-cannabinoid-agonist-win-55-212-2-during-early-adolescence-increases-alcohol-preference-and-anxiety-in-cd1-mice
#2
Jimena Laura Frontera, Victoria María Gonzalez Pini, Fernando Luis Messore, Alicia Brusco
The endocannabinoid (eCB) system is involved in the modulation of the reward system and participates in the reinforcing effects of different drugs of abuse, including alcohol. The most abundant receptor of the eCB system in the central nervous system is the CB1 receptor (CB1R), which is predominantly expressed in areas involved in drug addiction, such as the nucleus accumbens, the ventral tegmental area, the substantia nigra and the raphe nucleus. CB1R is expressed in early stages during development, and reaches maximum levels during early adolescence...
May 16, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29777724/novel-mirna-biomarkers-for-genotoxicity-screening-in-mouse
#3
Hiroyuki Oka, Koichi Masuno, Takeki Uehara, Toru Okamoto, Yoshiharu Matsuura, Toru Nakano, Shinpei Yamaguchi
The genotoxic potential of drugs is a serious problem, and its evaluation is one of the most critical processes of drug development. Although the comet assay of compound-exposed tissue is a frequently used genotoxicity test, its high false-positive rate is a major complication, and we consistently obtained false-positive results using the comet assay of mouse liver for nine hepatotoxic non-genotoxins (NGTXs). To identify novel genotoxin (GTX)-specific biomarkers, we screened the expression of 750 microRNAs (miRNAs) in the livers of mice treated with GTXs or NGTXs...
May 16, 2018: Toxicology
https://www.readbyqxmd.com/read/29777407/modelling-the-delay-between-pharmacokinetics-and-eeg-effects-of-morphine-in-rats-binding-kinetic-versus-effect-compartment-models
#4
Wilhelmus E A de Witte, Vivi Rottschäfer, Meindert Danhof, Piet H van der Graaf, Lambertus A Peletier, Elizabeth C M de Lange
Drug-target binding kinetics (as determined by association and dissociation rate constants, k on and k off ) can be an important determinant of the kinetics of drug action. However, the effect compartment model is used most frequently instead of a target binding model to describe hysteresis. Here we investigate when the drug-target binding model should be used in lieu of the effect compartment model. The utility of the effect compartment (EC), the target binding kinetics (TB) and the combined effect compartment-target binding kinetics (EC-TB) model were tested on either plasma (ECPL , TBPL and EC-TBPL ) or brain extracellular fluid (ECF) (ECECF , TBECF and EC-TBECF ) morphine concentrations and EEG amplitude in rats...
May 18, 2018: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/29777330/down-regulating-il-6-gp130-targets-improved-the-anti-tumor-effects-of-5-fluorouracil-in-colon-cancer
#5
Sanhong Li, Jilai Tian, Hongming Zhang, Shoubing Zhou, Xiyong Wang, Lei Zhang, Jiapeng Yang, Zhigang Zhang, Zhenling Ji
Recent studies have confirmed that IL-6/GP130 targets are closely associated with tumor growth, metastasis and drug resistance. 5-Fluorouracil (5-FU) is the most common chemotherapeutic agent for colon cancer but is limited due to chemoresistance and high cytotoxicity. Bazedoxifene (BZA), a third-generation selective estrogen receptor modulator, was discovered by multiple ligand simultaneous docking and drug repositioning approaches to have a novel function as an IL-6/GP130 target inhibitor. Thus, we speculated that in colon cancer, the anti-tumor efficacy of 5-FU might be increased in combination with IL-6/GP130 inhibitors...
May 18, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29775723/a-scale-out-approach-towards-neural-induction-of-human-induced-pluripotent-stem-cells-for-neurodevelopmental-toxicity-studies
#6
Cláudia C Miranda, Tiago G Fernandes, Sandra N Pinto, Manuel Prieto, M Margarida Diogo, Joaquim M S Cabral
Stem cell's unique properties confer them a multitude of potential applications in the fields of cellular therapy, disease modelling and drug screening fields. In particular, the ability to differentiate neural progenitors (NP) from human induced pluripotent stem cells (hiPSCs) using chemically-defined conditions provides an opportunity to create a simple and straightforward culture platform for application in these fields. Here, we demonstrated that hiPSCs are capable of undergoing neural commitment inside microwells, forming characteristic neural structures resembling neural rosettes and further give rise to glial and neuronal cells...
May 15, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29775322/prediction-of-human-cytochrome-p450-inhibition-using-a-multi-task-deep-autoencoder-neural-network
#7
Xiang Li, Youjun Xu, Luhua Lai, Jianfeng Pei
Adverse side effects of drug-drug interactions induced by human cytochrome P450 (CYP450) inhibition is an important consideration in drug discovery. It is highly desirable to develop computational models that can predict the inhibitive effect of a compound against a specific CYP450 isoform. In this study, we developed a multi-task model for concurrent inhibition prediction of five major CYP450 isoforms, namely 1A2, 2C9, 2C19, 2D6, and 3A4. The model was built by training multi-task autoencoder deep neural network (DNN) on a large dataset containing more than 13000 compounds, extracted from PubChem BioAssay Database...
May 18, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29774521/patient-reported-outcomes-of-multiple-myeloma-patients-treated-with-panobinostat-after-%C3%A2-2-lines-of-therapy-based-on-the-international-phase-3-randomized-double-blind-placebo-controlled-panorama-1-trial
#8
Paul G Richardson, Robert L Schlossman, Anuja N Roy, Ashok Panneerselvam, Suddhasatta Acharyya, Monika Sopala, Sagar Lonial
The phase 3 PANORAMA-1 trial led to regulatory approvals of panobinostat (PAN) in combination with bortezomib (BTZ) and dexamethasone (DEX) for the treatment of multiple myeloma after ≥2 prior regimens, including BTZ and an immunomodulatory drug. Patient-reported outcomes (PROs) were assessed in PANORAMA-1, with data available for 73 patients in the PAN + BTZ + DEX arm and 74 patients in the placebo (PBO) + BTZ + DEX arm. Per the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), global health status/quality of life (QoL) scores initially declined with PAN + BTZ + DEX during the first 24 weeks before approaching baseline scores and remaining steady during the next 24 weeks, with no difference between arms at Week 48...
May 17, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29774400/cost-effectiveness-of-osteoporosis-screening-strategies-for-hip-fracture-prevention-in-older-chinese-people-a-decision-tree-modeling-study-in-the-mr-os-and-ms-os-cohort-in-hong-kong
#9
Y Su, F T T Lai, B H K Yip, J C S Leung, T C Y Kwok
Despite the high costs of hip fracture, many governments provide limited support for osteoporosis screening. We demonstrated that osteoporosis screening by dual-energy X-ray absorptiometry (DXA) with or without pre-screening by Fracture Risk Assessment Tool (FRAX) or calcaneal ultrasound are more cost-effective than no screening in Chinese people aged 65 or over in Hong Kong. INTRODUCTION: To examine the cost-effective potential osteoporosis screening strategies for hip fracture prevention in Hong Kong...
May 17, 2018: Osteoporosis International
https://www.readbyqxmd.com/read/29774113/ezh2-inhibitors-sensitize-myeloma-cell-lines-to-panobinostat-resulting-in-unique-combinatorial-transcriptomic-changes
#10
Taylor Harding, Jessica Swanson, Brian Van Ness
Multiple myeloma (MM) remains a largely incurable hematologic cancer due to an inability to broadly target inevitable drug-resistant relapse. Epigenetic abnormalities are abundantly present in multiple myeloma and have increasingly demonstrated critical roles for tumor development and relapse to standard therapies. Accumulating evidence suggests that the histone methyltransferase EZH2 is aberrantly active in MM. We tested the efficacy of EZH2 specific inhibitors in a large panel of human MM cell lines (HMCLs) and found that only a subset of HMCLs demonstrate single agent sensitivity despite ubiquitous global H3K27 demethylation...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774093/distribution-of-virulence-associated-genes-and-antimicrobial-susceptibility-in-clinical-acinetobacter-baumannii-isolates
#11
Chao Liu, Yaowen Chang, Ying Xu, Yun Luo, Linrong Wu, Zhanjun Mei, Shigang Li, Rui Wang, Xu Jia
Acinetobacter baumannii is undoubtedly one of the most clinically significant pathogens. The multidrug resistance and virulence potential of A. baumannii are responsible for hospital-acquired nosocomial infections. Unlike numerous investigations on the drug-resistant epidemiology of A. baumanni , virulence molecular epidemiology is less studied. Here, we collected 88 A. baumannii clinical isolates, tested their antimicrobial susceptibility to 10 commonly used antibiotics and analyzed the distribution of 9 selected virulence-associated genes, aims to investigate the primary characteristics of the virulence-associated genes that exist in clinically multidrug resistant (MDR) and non-MDR isolates of A...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774074/placenta-specific-drug-delivery-by-trophoblast-targeted-nanoparticles-in-mice
#12
Baozhen Zhang, Lunbo Tan, Yan Yu, Baobei Wang, Zhilong Chen, Jinyu Han, Mengxia Li, Jie Chen, Tianxia Xiao, Balamurali K Ambati, Lintao Cai, Qing Yang, Nihar R Nayak, Jian Zhang, Xiujun Fan
Rationale: The availability of therapeutics to treat pregnancy complications is severely lacking, mainly due to the risk of harm to the fetus. In placental malaria, Plasmodium falciparum- infected erythrocytes (IEs) accumulate in the placenta by adhering to chondroitin sulfate A (CSA) on the surfaces of trophoblasts. Based on this principle, we have developed a method for targeted delivery of payloads to the placenta using a synthetic placental CSA-binding peptide (plCSA-BP) derived from VAR2CSA, a CSA-binding protein expressed on IEs...
2018: Theranostics
https://www.readbyqxmd.com/read/29773827/cardiac-pacemaker-channel-hcn4-inhibition-and-atrial-arrhythmogenesis-after-releasing-cardiac-sympathetic-activation
#13
Kristine Chobanyan-Jürgens, Karsten Heusser, David Duncker, Christian Veltmann, Marcus May, Heidrun Mehling, Friedrich C Luft, Christoph Schröder, Jens Jordan, Jens Tank
Clinical trials and studies with ivabradine implicate cardiac pacemaker channels (HCN4) in the pathogenesis of atrial arrhythmias. Because acute changes in cardiac autonomic tone predispose to atrial arrhythmias, we studied humans in whom profound cardiac sympathetic activation was rapidly relieved to test influences of HCN4 inhibition with ivabradine on atrial arrhythmias. We tested 19 healthy participants with ivabradine, metoprolol, or placebo in a double blind, randomized, cross-over fashion on top of selective norepinephrine reuptake inhibition with reboxetine...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29773696/electroacupuncture-as-a-complement-to-usual-care-for-patients-with-non-acute-low-back-pain-after-back-surgery-a-pilot-randomised-controlled-trial
#14
In Heo, Man-Suk Hwang, Eui-Hyoung Hwang, Jae-Heung Cho, In-Hyuk Ha, Kyung-Min Shin, Jun-Hwan Lee, Nam-Kwen Kim, Dong-Wuk Son, Byung-Cheul Shin
OBJECTIVES: The aim of this pilot study was to estimate the sample size for a large pragmatic study of the comparative effectiveness of electroacupuncture (EA) for low back pain (LBP) after back surgery. DESIGN: A randomised, active-controlled, assessor-blinded trial. PARTICIPANTS: Patients with recurrent or persistent LBP, defined as a Visual Analogue Scale (VAS) score of ≥50 mm, with or without leg pain after back surgery. INTERVENTIONS: Patients were randomised to an EA plus usual care (UC) group or to a UC alone group at a 1:1 ratio...
May 17, 2018: BMJ Open
https://www.readbyqxmd.com/read/29773302/experiences-and-perceptions-of-black-men-who-have-sex-with-men-about-acquiring-hiv-a-qualitative-narrative-perspective
#15
Austin Nation, Catherine M Waters, Carol Dawson-Rose
In the United States, Black men who have sex with men (MSM), between the ages of 18 and 34 years, have the highest rates of new HIV infections. The prevalence of HIV in this population is three to four times higher than their White MSM counterparts. Twelve Black MSM from the Bay Area, nine with HIV and three without HIV, were interviewed regarding their experiences and perceived risks of acquiring HIV. Narrative analysis revealed these themes: (a) tested regularly for HIV, (b) HIV knowledge varied before arriving in San Francisco, (c) condom use typically nonexistent when under the influence of alcohol and other drugs, (d) inability to negotiate sex and condom usage, and (e) sense of anticipation, resignation, and acceptance about acquiring HIV...
April 25, 2018: Journal of the Association of Nurses in AIDS Care: JANAC
https://www.readbyqxmd.com/read/29773092/preliminary-study-on-drug-susceptibility-profile-and-resistance-mechanisms-to-macrolides-of-clinical-isolates-of-non-tuberculous-mycobacteria-from-china
#16
Fu Li, Gui Lian Li, Hui Pang, Hai Can Liu, Tong Yang Xiao, Shuang Jun Li, Qiao Luo, Yi Jiang, Rui Bai Wang, Kang Lin Wan
OBJECTIVE: Macrolide susceptibility and drug resistance mechanisms of clinical non-tuberculous mycobacteria (NTM) isolates were preliminarily investigated for more accurate diagnosis and treatment of the infection in China. METHODS: Four macrolides, including clarithromycin (CLAR), azithromycin (AZM), roxithromycin (ROX), and erythromycin (ERY), were used to test the drug susceptibility of 310 clinical NTM isolates from six provinces of China with the broth microdilution method...
April 2018: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/29772697/structure-activity-relationships-based-on-3d-qsar-comfa-comsia-and-design-of-aryloxypropanol-amine-agonists-with-selectivity-for-the-human-%C3%AE-3-adrenergic-receptor-and-anti-obesity-and-anti-diabetic-profiles
#17
Marcos Lorca, Cesar Morales-Verdejo, David Vásquez-Velásquez, Juan Andrades-Lagos, Javier Campanini-Salinas, Jorge Soto-Delgado, Gonzalo Recabarren-Gajardo, Jaime Mella
The wide tissue distribution of the adrenergic β3 receptor makes it a potential target for the treatment of multiple pathologies such as diabetes, obesity, depression, overactive bladder (OAB), and cancer. Currently, there is only one drug on the market, mirabegron, approved for the treatment of OAB. In the present study, we have carried out an extensive structure-activity relationship analysis of a series of 41 aryloxypropanolamine compounds based on three-dimensional quantitative structure-activity relationship (3D-QSAR) techniques...
May 16, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29772021/analysis-of-risk-factors-for-mild-cognitive-impairment-based-on-word-list-memory-test-results-and-questionnaire-responses-in-healthy-japanese-individuals-registered-in-an-online-database
#18
Masayo Ogawa, Daichi Sone, Kazushi Maruo, Hiroyuki Shimada, Keisuke Suzuki, Hiroshi Watanabe, Hiroshi Matsuda, Hidehiro Mizusawa
Although the development of effective therapeutic drugs and radical treatment options for dementia and Alzheimer's disease (AD) remains urgent, progress in recent clinical trials of AD drugs has been less than adequate. In order to advance the progress of clinical trials, it is necessary to establish more efficient methods of recruitment. In Japan, there are registration systems stratified by mild cognitive impairment and preclinical and clinical stages of early and advanced stage dementia, but there is no registration system for healthy individuals yet...
2018: PloS One
https://www.readbyqxmd.com/read/29771559/body-mass-index-across-adolescence-and-substance-use-problems-in-early-adulthood
#19
Ashley N Gearhardt, Rebecca Waller, Jennifer M Jester, Luke W Hyde, Robert A Zucker
Excessive substance use and obesity are underpinned by a number of shared risk factors (e.g., reward dysfunction, impulsivity). Food and drugs of abuse engage similar reward-related neural circuitry and the food-drug competition hypothesis proposes that excess consumption of food may diminish desire for drugs of abuse by competing for neural receptors associated with reward and motivation. Adolescence is a high-risk period for both increased substance use and excessive weight gain. In the present study, the authors tested whether, consistent with the food-drug competition hypothesis, elevated body mass index (BMI) across adolescence predicted fewer substance use problems in young adulthood...
May 2018: Psychology of Addictive Behaviors: Journal of the Society of Psychologists in Addictive Behaviors
https://www.readbyqxmd.com/read/29770539/hepatitis-b-virus-reactivation-in-patients-with-rheumatoid-arthritis-analysis-of-the-national-database-of-japan
#20
Misuzu Fujita, Masaya Sugiyama, Yasunori Sato, Kengo Nagashima, Sho Takahashi, Masashi Mizokami, Akira Hata
This study aimed to determine the incidence and risk factors for hepatitis B virus (HBV) reactivation in patients with rheumatoid arthritis (RA) undergoing immunosuppressive therapy. The National Database of Japan, in which insurance claim data have been comprehensively accumulated, was utilized. The subjects were 76,641 RA patients who were plausibly initiated on immunosuppressive therapy from April 2013 to March 2014. Laboratory tests of the hepatitis B surface antigen, anti-hepatitis B virus surface antibody, and anti-hepatitis B virus core antibody were performed in 28...
May 16, 2018: Journal of Viral Hepatitis
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