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https://www.readbyqxmd.com/read/28320043/effects-of-ranolazine-in-a-model-of-doxorubicin-induced-left-ventricle-diastolic-dysfunction
#1
Donato Cappetta, Grazia Esposito, Raffaele Coppini, Elena Piegari, Rosa Russo, Loreta Pia Ciuffreda, Alessia Rivellino, Lorenzo Santini, Concetta Rafaniello, Cristina Scavone, Francesco Rossi, Liberato Berrino, Konrad Urbanek, Antonella De Angelis
BACKGROUND AND PURPOSE: Doxorubicin (DOXO) is a highly effective anticancer drug but its clinical application is impeded by cardiotoxicity. Asymptomatic diastolic dysfunction can be the earliest manifestation of DOXO cardiotoxicity. Therefore, a search for therapeutic intervention that can interfere with early manifestations and possibly prevent late cardiotoxicity is warranted. Increased DOXO-dependent reactive oxygen species may explain, in part, Ca(2+) and Na(+) overload that contributes to diastolic dysfunction and development of heart failure...
March 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28320042/calcium-channel-modulation-as-a-target-in-chronic-pain-control
#2
REVIEW
Ryan Patel, Carlota Montagut-Bordas, Anthony H Dickenson
Neuropathic pain remains poorly treated for large numbers of patients and little progress has been made in developing novel classes of analgesics. To redress this issue, ziconotide (Prialt(TM) ) was developed and approved as a first in class synthetic version of ω-conotoxin MVIIA, a Cav 2.2 peptide blocker. Unfortunately, the impracticalities of intrathecal delivery, low therapeutic index and severe neurological side effects associated with ziconotide has restricted its use to exceptional circumstances. Ziconotide exhibits no state or use dependent block of Cav 2...
March 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28319830/anti-proliferative-effect-of-metformin-on-a-feline-injection-site-sarcoma-cell-line-independent-of-mtor-inhibition
#3
J Pierro, C Saba, K McLean, R Williams, E Karpuzoglu, R Prater, K Hoover, R Gogal
Metformin is an oral hypoglycemic drug that has been shown to inhibit cancer cell proliferation via up-regulation of AMPK (AMP-activated protein kinase), and possibly inhibition of mTOR (mammalian target of rapamycin). The purpose of this study was to evaluate the effects of metformin on a feline injection site sarcoma cell line. Cells from a feline injection site sarcoma cell line were treated with metformin at varied concentrations. A dose-dependent decrease in cell viability following metformin treatment was observed, with an IC50 of 8...
March 6, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28319750/unfavorable-effect-of-levetiracetam-on-cultured-hippocampal-neurons-after-hyperthermic-injury
#4
Krzysztof Sendrowski, Piotr Sobaniec, Elżbieta Poskrobko, Małgorzata Rusak, Wojciech Sobaniec
BACKGROUND: The aim of this study was to examine the viability of neurons and the putative neuroprotective effects of second-generation antiepileptic drug, levetiracetam (LEV), on cultured hippocampal neurons injured by hyperthermia. METHODS: Primary cultures of rat's hippocampal neurons at 7day in vitro (DIV) were incubated in the presence or absence of LEV in varied concentrations under hyperthermic conditions. Cultures were heated in a temperature of 40°C for 24h or in a temperature of 41°C for 6h...
January 24, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28319473/precision-medicine-in-asthma-the-role-of-bronchial-thermoplasty
#5
Amber J Oberle, Praveen Mathur
PURPOSE OF REVIEW: The inflammatory makeup of severe asthma is heterogeneous. Identification of the predominant cellular endotype via biomarkers can aid in the selection of more advanced therapies. This review is clinically focused on how to use these biomarkers to help select between biologic agents and/or bronchial thermoplasty. RECENT FINDINGS: Several Th2 biomarkers exist for the detection of eosinophilic disease; however, the best biomarker for clinical practice is debatable depending upon local resources...
March 17, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28319159/drug-therapy-for-alcohol-dependence-in-primary-care-in-the-uk-a-clinical-practice-research-datalink-study
#6
Andrew Thompson, Darren M Ashcroft, Lynn Owens, Tjeerd P van Staa, Munir Pirmohamed
AIM: To evaluate drug therapy for alcohol dependence in the 12 months after first diagnosis in UK primary care. DESIGN: Open cohort study. SETTING: General practices contributing data to the UK Clinical Practice Research Database. PARTICIPANTS: 39,980 people with an incident diagnosis of alcohol dependence aged 16 years or older between 1 January 1990 and 31 December 2013. MAIN OUTCOME MEASURE: Use of pharmacotherapy (acamprosate, disulfiram, naltrexone, baclofen and topiramate) to promote abstinence from alcohol or reduce drinking to safe levels in the first 12 months after a recorded diagnosis of alcohol dependence...
2017: PloS One
https://www.readbyqxmd.com/read/28319043/glucocorticoid-receptors-finding-the-middle-ground
#7
Sofie J Desmet, Karolien De Bosscher
Glucocorticoids (GCs; referred to clinically as corticosteroids) are steroid hormones with potent anti-inflammatory and immune modulatory profiles. Depending on the context, these hormones can also mediate pro-inflammatory activities, thereby serving as primers of the immune system. Their target receptor, the GC receptor (GR), is a multi-tasking transcription factor, changing its role and function depending on cellular and organismal needs. To get a clearer idea of how to improve the safety profile of GCs, recent studies have investigated the complex mechanisms underlying GR functions...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28318754/differences-between-men-and-women-in-substance-use-the-role-of-educational-level-and-employment-status
#8
Ester Teixidó-Compañó, Albert Espelt, Luis Sordo, María J Bravo, Ana Sarasa-Renedo, B Iciar Indave, Marina Bosque-Prous, M Teresa Brugal
OBJECTIVE: To determine differences between men and women in hazardous drinking, heavy cannabis use and hypnosedative use according to educational level and employment status in the economically active population in Spain. METHOD: Cross-sectional study with data from 2013 Spanish Household Survey on Alcohol and Drugs on individuals aged 25-64 [n=14,113 (women=6,171; men=7,942)]. Dependent variables were hazardous drinking, heavy cannabis use and hypnosedative consumption; the main independent variables were educational level and employment situation...
March 15, 2017: Gaceta Sanitaria
https://www.readbyqxmd.com/read/28317899/minocycline-treatment-suppresses-juvenile-development-and-growth-by-attenuating-insulin-tor-signaling-in-drosophila-animal-model
#9
Hyun Myoung Yun, Sujin Noh, Seogang Hyun
Minocycline is a broad spectrum, semi-synthetic tetracycline analog that is used to treat bacterial infection. Recently, this drug has been receiving increasing attention for its non-antibiotic properties, including anti-inflammatory, tumor suppressive, and neuroprotective effects. Drosophila is a useful model organism for studying human metabolism and disease. In this study, we investigated the effects of minocycline on juvenile development and growth in Drosophila. Feeding minocycline to Drosophila larvae suppresses larval body growth and delays the timing of pupation in a dose-dependent manner...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317872/preclinical-evaluation-of-the-efficacy-pharmacokinetics-and-immunogenicity-of-js-001-a-programmed-cell-death-protein-1-pd-1-monoclonal-antibody
#10
Jie Fu, Fang Wang, Li-Hou Dong, Jing Zhang, Cheng-Lian Deng, Xue-Li Wang, Xin-Yao Xie, Jing Zhang, Ruo-Xian Deng, Li-Bo Zhang, Hai Wu, Hui Feng, Bo Chen, Hai-Feng Song
JS-001 is the first monoclonal antibody (mAb) against programmed cell death protein-1 (PD-1) approved by the China Food and Drug Administration (CFDA) into the clinical trails. To date, however, no pre-clinical pharmacological and pharmacokinetic (PK) data are available. In this study, we investigated the efficacy of JS-001 and conducted a preclinical PK study, including the monitoring of anti-drug antibodies (ADAs). We found that JS-001 specifically bound to PD-1 antigen with an EC50 of 21 nmol/L, and competently blocked the binding of PD-1 antigen to PD-L1 and PD-L2 with IC50 of 3...
March 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28317805/prevalence-and-genetic-determinant-of-drug-resistant-tuberculosis-among-patients-completing-intensive-phase-of-treatment-in-a-tertiary-referral-center-in-nigeria
#11
Aminu Bashir Mohammad, Garba Iliyasu, Abdulrazaq Garba Habib
BACKGROUND: Drug-resistant tuberculosis (DR-TB) continues to be a challenge in developing countries with poor resources. Despite the high prevalence of primary DR-TB, its routine screening prior to the treatment is not performed in public hospitals in Nigeria. Data regarding drug resistance and its genetic determinant among follow-up patients with TB are lacking in Nigeria. Hence, the aim of this study was to determine the prevalence and genetic determinant of drug resistance among the follow-up patients with TB in a tertiary hospital in Nigeria...
January 2017: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28317506/theory-of-mind-impairments-in-women-with-cocaine-addiction
#12
Breno Sanvicente-Vieira, Bruno Kluwe-Schiavon, Rhiannon Corcoran, Rodrigo Grassi-Oliveira
OBJECTIVE: This study investigates the Theory of Mind performance of female cocaine-dependent users (CDUs) and possible associations between theory of mind performance and features of cocaine use. METHOD: Sixty women controlled for age, education, individual income, and IQ participated in this study: 30 in the CDU group and 30 in the healthy control group. Participants were assessed for theory of mind with the Reading the Mind in the Eyes Test (RMET), a test of understanding of first-order and second-order false beliefs, and the Hinting task...
March 2017: Journal of Studies on Alcohol and Drugs
https://www.readbyqxmd.com/read/28317271/baclofen-and-alcohol-dependent-patients-a-real-risk-of-severe-self-poisoning
#13
David Boels, Caroline Victorri-Vigneau, Marie Grall-Bronnec, Ali Touré, Anais Garnier, Alain Turcant, Gaël Le Roux
Baclofen is often prescribed in high doses to fight cravings experienced by alcohol-dependent patients. Such an increase in the availability of baclofen is concerning. This study aimed to determine the change in number and profile of self-poisoning with baclofen over time, since baclofen has become increasingly popular, in order to describe the severity of self-poisoning with baclofen and to focus on co-existing alcohol use disorders and psychiatric illnesses determine predictors of severity. This was a retrospective study of self-poisoning with baclofen as reported by the western France Poison Control Center (PCC), which represents a population of more than 12 million people from January 2008 to March 2014...
March 19, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28317259/a-prospective-study-of-the-substance-use-and-mental-health-outcomes-of-young-adult-former-and-current-cannabis-users
#14
Edmund Silins, Wendy Swift, Tim Slade, Barbara Toson, Bryan Rodgers, Delyse M Hutchinson
INTRODUCTION AND AIMS: The extent to which young adult former cannabis users fare better than infrequent users is unclear. We investigated the association between cannabis use status at age 23 and substance use and mental health outcomes at age 27. DESIGN AND METHODS: Data were from the 20+ year cohort of the PATH Through Life Study. Lifetime cannabis users (n = 1410) at age 23 were classified as former/occasional/regular users. Multivariable logistic regression was used to estimate the association between cannabis use status at age 23 and six outcomes assessed at age 27...
March 20, 2017: Drug and Alcohol Review
https://www.readbyqxmd.com/read/28317200/self-limiting-non-medical-pharmaceutical-opioid-use-among-young-people-in-sydney-australia-an-exploratory-study
#15
George C Dertadian, Thomas C Dixon, Jennifer Iversen, Lisa Maher
INTRODUCTION AND AIMS: Indicators suggest an escalation in opioid use globally, with recent HIV outbreaks linked to non-medical pharmaceutical opioid (NMPO) use. Little is known about how young Australians engage in NMPO use. DESIGN AND METHODS: During 2015, we conducted qualitative interviews with young people (16-29 years) who reported oral NMPO use at least twice in the past 90 days. The study included a sample of injecting (n = 14) and oral (n = 22) users...
March 20, 2017: Drug and Alcohol Review
https://www.readbyqxmd.com/read/28317069/deciphering-the-role-of-ectosomes-in-cancer-development-and-progression-focus-on-the-proteome
#16
REVIEW
Magdalena Surman, Ewa Stępień, Dorota Hoja-Łukowicz, Małgorzata Przybyło
Ectosomes are small heterogeneous membrane vesicles generated by budding from the plasma membrane in a variety of cell types and, more frequently, in tumor cells. They are shed into the extracellular space and are proposed as a novel form of intracellular communication in which information is transmitted from the originating cell to recipient cells without direct cell-to-cell contact. This review focuses on a single population of extracellular vesicles-ectosomes. We summarize recent studies of tumor-derived ectosomes which examine their biogenesis and protein cargo, and their influence on different aspects of cancer progression...
March 19, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28317028/mycobacterial-caseinolytic-protease-gene-regulator-clgr-is-a-substrate-of-caseinolytic-protease
#17
Yoshiyuki Yamada, Thomas Dick
The mycobacterial caseinolytic protease ClpP1P2 is a degradative protease that recently gained interest as a genetically and pharmacologically validated drug target for tuberculosis. The first whole-cell active ClpP1P2 inhibitor, the human proteasome inhibitor bortezomib, is currently undergoing lead optimization to introduce selectivity for the bacterial target. How inhibition of ClpP1P2 translates into whole-cell antimicrobial activity is little understood. Previous work has shown that the caseinolytic protease gene regulator ClgR is an activator of the clpP1P2 genes and also suggested that this transcription factor may be a substrate of the protease...
March 2017: MSphere
https://www.readbyqxmd.com/read/28315808/benzodiazepine-z-drug-and-pregabalin-prescriptions-and-mortality-among-patients-in-opioid-maintenance-treatment-a-nation-wide-register-based-open-cohort-study
#18
Tove Abrahamsson, Jonas Berge, Agneta Öjehagen, Anders Håkansson
BACKGROUND: Use of sedatives may increase risk of death in opioid users. The aim of the study was to assess whether prescription of sedatives may be associated with mortality in patients in opioid maintenance treatment. METHODS: This retrospective register-based open cohort study included nation-wide register data including all individuals who were dispensed methadone or buprenorphine as opioid maintenance treatment for opioid dependence between July, 2005 and December, 2012 (N=4501)...
February 28, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28315700/exploiting-the-aglycon-promiscuity-of-glycosyltransferase-bs-yjic-from-bacillus-subtilis-and-its-application-in-synthesis-of-glycosides
#19
Longhai Dai, Jiao Li, Peiyuan Yao, Yueming Zhu, Yan Men, Yan Zeng, Jiangang Yang, Yuanxia Sun
Glycosylation is a prominent biological mechanism for structural and functional diversity of natural products. Uridine diphosphate-dependent glycosyltransferases with aglycon promiscuity are generally recognised as effective biocatalysts for glycodiversification of natural products for practical applications. In this study, the aglycon promiscuity of glycosyltransferase Bs-YjiC from Bacillus subtilis 168 was explored. Bs-YjiC, with uridine diphosphate glucose (UDPG) as sugar donor, exhibited robust capabilities to glycosylate 19 structurally diverse types of drug-like scaffolds with regio- and stereospecificities and form O-, N- and S-linkage glycosides...
March 15, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28315467/hce-t-cell-based-permeability-model-a-well-maintained-or-a-highly-variable-barrier-phenotype
#20
Marina Juretić, Bisera Jurišić Dukovski, Iva Krtalić, Stephan Reichl, Biserka Cetina-Čižmek, Jelena Filipović-Grčić, Jasmina Lovrić, Ivan Pepić
The most extensively characterized human-derived cell line used in transcorneal permeability studies, in terms of passive transcellular and paracellular transport, transporter expression and metabolic enzymes, is the immortalized human corneal epithelial cell line (HCE-T). The purpose of this study is to describe the changes in the HCE-T barrier phenotype in vitro when valid cultivation conditions, in accordance with the standardized HCE-T cell-based model protocol, were employed. Evaluation of the structural and functional barrier properties revealed two different HCE-T barrier phenotypes, depending on the polycarbonate membrane pore size...
March 14, 2017: European Journal of Pharmaceutical Sciences
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