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Clinical pharmacology

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https://www.readbyqxmd.com/read/28334857/co-cultures-with-stem-cell-derived-human-sensory-neurons-reveal-regulators-of-peripheral-myelination
#1
Alex J Clark, Malte S Kaller, Jorge Galino, Hugh J Willison, Simon Rinaldi, David L H Bennett
Effective bidirectional signalling between axons and Schwann cells is essential for both the development and maintenance of peripheral nerve function. We have established conditions by which human induced pluripotent stem cell-derived sensory neurons can be cultured with rat Schwann cells, and have produced for the first time long-term and stable myelinating co-cultures with human neurons. These cultures contain the specialized domains formed by axonal interaction with myelinating Schwann cells, such as clustered voltage-gated sodium channels at the node of Ranvier and Shaker-type potassium channel (Kv1...
February 15, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334843/a152t-tau-allele-causes-neurodegeneration-that-can-be-ameliorated-in-a-zebrafish-model-by-autophagy-induction
#2
Ana Lopez, Suzee E Lee, Kevin Wojta, Eliana Marisa Ramos, Eric Klein, Jason Chen, Adam L Boxer, Maria Luisa Gorno-Tempini, Daniel H Geschwind, Lars Schlotawa, Nikolay V Ogryzko, Eileen H Bigio, Emily Rogalski, Sandra Weintraub, Marsel M Mesulam, Angeleen Fleming, Giovanni Coppola, Bruce L Miller, David C Rubinsztein
Mutations in the gene encoding tau (MAPT) cause frontotemporal dementia spectrum disorders. A rare tau variant p.A152T was reported as a risk factor for frontotemporal dementia spectrum and Alzheimer's disease in an initial case-control study. Such findings need replication in an independent cohort. We analysed an independent multinational cohort comprising 3100 patients with neurodegenerative disease and 4351 healthy control subjects and found p.A152T associated with significantly higher risk for clinically defined frontotemporal dementia and progressive supranuclear palsy syndrome...
February 9, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334567/review-of-nonformulary-medication-approvals-in-an-academic-medical-center
#3
Qoua L Her, Mary G Amato, Diane L Seger, James F Gilmore, John Fanikos, Julie M Fiskio, David W Bates
BACKGROUND: The Joint Commission requires hospitals to formally review formulary medications at least annually based on new clinical information. Although review of nonformulary medication (NFM) use is not required, frequent and inappropriate use of NFMs has the potential to increase hospital costs, negatively affect quality of care, and increase medication errors. Limited resources may restrict an institution's ability to review NFM use in addition to the required annual formulary review...
February 2017: Joint Commission Journal on Quality and Patient Safety
https://www.readbyqxmd.com/read/28333661/does-your-drug-expertise-include-clinical-pharmaceutics
#4
David W Newton
Whose job is it to protect patients from harm from drug instabilities and incompatibilities and other aspects of clinical pharmaceutics? Pharmacists are better educated via multiple required general and organic chemistry prerequisite and professional curricula medicinal chemistry and pharmaceutics courses. Therefore, no healthcare professional other than pharmacists are nicknamed drug experts or are better formally educated to master drug chemistry in the bottle (i.e., injection stability and compatibility/incompatibility clinical pharmaceutics) as a prerequisite for drug administration to cause safe and effective drug chemistry in the body (i...
May 2016: International Journal of Pharmaceutical Compounding
https://www.readbyqxmd.com/read/28333250/the-complexity-of-minocycline-serum-protein-binding
#5
Jian Zhou, Brian T Tran, Vincent H Tam
Objectives: Serum protein binding is critical for understanding the pharmacology of antimicrobial agents. Tigecycline and eravacycline were previously reported to have atypical non-linear protein binding; the percentage of free fraction decreased with increasing total concentration. In this study, we extended the investigation to other tetracyclines and examined the factors that might impact protein binding. Methods: Different minocycline concentrations (0.5-50 mg/L) and perfusion media (saline, 0...
February 25, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28332584/akt-targeting-as-a-strategy-to-boost-chemotherapy-efficacy-in-non-small-cell-lung-cancer-through-metabolism-suppression
#6
Marion Le Grand, Raphael Berges, Eddy Pasquier, Marie-Pierre Montero, Laurence Borge, Alice Carrier, Sophie Vasseur, Veronique Bourgarel, Duje Buric, Nicolas André, Diane Braguer, Manon Carré
Metabolic reprogramming is a hallmark of cancer development, mediated by genetic and epigenetic alterations that may be pharmacologically targeted. Among oncogenes, the kinase Akt is commonly overexpressed in tumors and favors glycolysis, providing a rationale for using Akt inhibitors. Here, we addressed the question of whether and how inhibiting Akt activity could improve therapy of non-small cell lung cancer (NSCLC) that represents more than 80% of all lung cancer cases. First, we demonstrated that Akt inhibitors interacted synergistically with Microtubule-Targeting Agents (MTAs) and specifically in cancer cell lines, including those resistant to chemotherapy agents and anti-EGFR targeted therapies...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332488/parkinson-disease
#7
REVIEW
Werner Poewe, Klaus Seppi, Caroline M Tanner, Glenda M Halliday, Patrik Brundin, Jens Volkmann, Anette-Eleonore Schrag, Anthony E Lang
Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability...
March 23, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28332422/effect-of-methotrexate-on-bone-and-wound-healing
#8
Ippokratis Pountos, Peter V Giannoudis
INTRODUCTION: Methotrexate (MTX) is one of the most commonly used disease modifying drugs administered for wide spectrum of conditions. Through the expansion of the indications of MTX use, an increasing number of patients nowadays attend orthopaedic departments receiving this pharmacological agent. The aim of this manuscript is to present our current understanding on the effect of MTX on bone and wound healing. AREAS COVERED: The authors offer a comprehensive review of the existing literature on the experimental and clinical studies analysing the effect of MTX on bone and wound healing...
March 23, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28332230/screening-and-identification-of-multiple-constituents-and-their-metabolites-of-zhi-zi-chi-decoction-in-rat-urine-and-bile-by-uplc-q-tof-ms-ms
#9
Wei Feng, Qiuju Dong, Minyan Liu, Si Li, Ting Liu, Xinguo Wang, Liying Niu
Zhi-zi-chi decoction (ZZCD) is a classical formula widely used in Chinese clinical application. In the present study, a novel and efficient strategy has been developed for screening and identification of multiple constituents and their metabolites of ZZCD using ultra high performance liquid chromatography combined with triple TOF mass spectrometry. The novel approach of an on-line data acquisition method dependent on multiple mass defect filter and dynamic background subtraction is combined with multiple data processing techniques...
March 23, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28332123/self-poisoning-suicide-deaths-in-people-with-bipolar-disorder-characterizing-a-subgroup-and-identifying-treatment-patterns
#10
Ayal Schaffer, Lauren M Weinstock, Mark Sinyor, Catherine Reis, Benjamin I Goldstein, Lakshmi N Yatham, Anthony J Levitt
OBJECTIVE: To characterize self-poisoning suicide deaths in BD compared to other suicide decedents. METHODS: Extracted coroner data from all suicide deaths (n = 3319) in Toronto, Canada from 1998 to 2012. Analyses of demographics, clinical history, recent stressors, and suicide details were conducted in 5 subgroups of suicide decedents: BD self-poisoning, BD other methods, non-BD self-poisoning, non-BD other methods, and unipolar depression self-poisoning. Toxicology results for lethal and present substances were also compared between BD and non-BD self-poisoning subgroups as well as between BD and unipolar depression self-poisoning subgroups...
December 2017: International Journal of Bipolar Disorders
https://www.readbyqxmd.com/read/28332047/mechanisms-of-resistance-to-target-therapies-in-non-small-cell-lung-cancer
#11
Francesco Facchinetti, Claudia Proto, Roberta Minari, Marina Garassino, Marcello Tiseo
Targeted therapies are revolutionizing the treatment of advanced non-small cell lung cancer (NSCLC). The discovery of key oncogenic events mainly in lung adenocarcinoma, like EGFR mutations or ALK rearrangements, has changed the treatment landscape while improving the prognosis of lung cancer patients. Inevitably, virtually all patients initially treated with targeted therapies develop resistance because of the emergence of an insensitive cellular population, selected by pharmacologic pressure. Diverse mechanisms of resistance, in particular to EGFR, ALK and ROS1 tyrosine-kinase inhibitors (TKIs), have now been discovered and may be classified in three different groups: (1) alterations in the target (such as EGFR T790M and ALK or ROS1 mutations); (2) activation of alternative pathways (i...
March 23, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28331986/renal-function-preservation-with-pioglitazone-or-with-basal-insulin-as-an-add-on-therapy-for-patients-with-type-2-diabetes-mellitus
#12
Yu-Hung Chang, Der-Wei Hwu, Dao-Ming Chang, Ling-Wang An, Chang-Hsun Hsieh, Yau-Jiunn Lee
AIMS: Clinical outcome may differ owing to the distinct pharmacological characteristics of insulin sensitizers and insulin. This study was performed to compare the metabolic and renal function changes with add-on pioglitazone treatment versus basal insulin in patients with type 2 diabetes mellitus (DM) in whom sulfonylurea and metformin regimens failed. METHODS: Patients who were consecutively managed in the diabetes comprehensive program with add-on pioglitazone or detemir/glargine treatment for at least 2 years following sulfonylurea and metformin treatment failure were included...
March 22, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28331332/clinical-role-of-brexpiprazole-in-depression-and-schizophrenia
#13
REVIEW
Nishant B Parikh, Diana M Robinson, Anita H Clayton
Brexpiprazole, a serotonin-dopamine activity modulator, is the second D2 partial agonist to come to market and has been approved for the treatment of schizophrenia and as an adjunctive treatment in major depressive disorder. With less intrinsic activity than aripiprazole at the D2 receptor and higher potency at 5-HT2A, 5-HT1A, and α1B receptors, the pharmacological properties of brexpiprazole suggest a more tolerable side effect profile with regard to akathisia, extrapyramidal dysfunction, and sedation. While no head-to-head data are currently available, double-blind placebo-controlled studies show favorable results, with the number needed to treat (NNT) vs placebo of 6-15 for response in acute schizophrenia treatment and 4 for maintenance...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28331172/an-anti-coagulation-conundrum-implantation-of-total-artificial-heart-in-a-patient-with-heparin-induced-thrombocytopenia-type-ii
#14
Theodore J Cios, Yuliana Salamanca-Padilla, Dmitri Guvakov
BACKGROUND Heparin-induced thrombocytopenia (HIT) is a rare but life-threatening complication of heparin administration. It can present a major clinical dilemma for physicians caring for patients requiring life-saving urgent or emergent cardiac surgery. Studies have been published examining the use of alternative anticoagulants for patients undergoing cardiopulmonary bypass (CPB), however, evidence does not clearly support any particular approach. Presently, there are no large-scale, prospective randomized studies examining the impact of alternative anticoagulants on clinical outcomes for HIT-positive patients requiring cardiac surgery...
March 23, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28330724/treatment-effects-and-mechanisms-of-yujin-powder-on-rat-model-of-large-intestine-dampness-heat-syndrome
#15
Wanling Yao, Chaoxue Yang, Yanqiao Wen, Wangdong Zhang, Xiaosong Zhang, Qi Ma, Peng Ji, Yongli Hua, Yanming Wei
ETHNOPHARMACOLOGICAL RELEVANCE: Yujin Powder (YJP), an old prescription, is one of the most classical prescription for treating the large intestine dampness-heat syndrome (LIDHS). However, its potential modern pharmacological mechanisms remain unclear. AIM OF THE STUDY: The present study was designed to explore the essence of LIDHS and treatment mechanisms of the YJP on the LIDHS. METHODS: The rat model of LIDHS was established by such complex factors as high-sugar and high-fat diet, improper diet, high temperature and humidity environment (HTHE), drinking and intraperitoneal injection of Escherichia coli...
March 19, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28329750/optoelectronic-plethysmography-in-clinical-practice-and-research-a-review
#16
Carlo Massaroni, Elena Carraro, Andrea Vianello, Sandra Miccinilli, Michelangelo Morrone, Irisz K Levai, Emiliano Schena, Paola Saccomandi, Silvia Sterzi, John W Dickinson, Samantha Winter, Sergio Silvestri
BACKGROUND: Optoelectronic plethysmography (OEP) is a non-invasive motion capture method to measure chest wall movements and estimate lung volumes. OBJECTIVES: To provide an overview of the clinical findings and research applications of OEP in the assessment of breathing mechanics across populations of healthy and diseased individuals. METHODS: A bibliographic research was performed with the terms "opto-electronic plethysmography," "optoelectronic plethysmography," and "optoelectronic plethysmograph" in 50 digital library and bibliographic search databases resulting in the selection of 170 studies...
March 23, 2017: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/28329729/prodrugs-of-triterpenoids-and-their-derivatives
#17
REVIEW
Meng Zhou, Rong-Hong Zhang, Min Wang, Guo-Bo Xu, Shang-Gao Liao
Triterpenoids are structurally diverse organic compounds that exist widely as natural products. Triterpenoids and their derivatives possess a wide range of biological effects including hepatoprotective, hypoglycemic, immunomodulatory, anti-inflammatory, anti-oxidant, and antitumor activities. In particular, the lupane-, oleanane-, and ursane-type triterpenes have been reported to exhibit pharmacological effects without prominent toxicity even at higher concentrations. Whereas, the poor drug-like properties (e...
March 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28328764/simultaneous-determination-of-protein-unbound-cyclosporine-a-and-mycophenolic-acid-in-kidney-transplant-patients-using-liquid-chromatography-tandem-mass-spectrometry
#18
Heike Bittersohl, Juliane Herbinger, Ming Wen, Lutz Renders, Werner Steimer, Peter B Luppa
BACKGROUND: Therapeutic drug monitoring (TDM) of immunosuppressants is essential to optimize patient care after organ transplantation. In blood, most immunosuppressive drugs are bound to plasma proteins or located inside blood cells. However, it is generally assumed that only protein-unbound (free) drug concentrations are pharmacologically active and could therefore better reflect the clinical outcome. Study data are still limited due to lacking rapid analytical methods. Therefore, a simple multiplex method for direct measurement of free cyclosporine A (CsA) and mycophenolic acid (MPA) has been developed...
March 21, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28328711/management-of-atrial-fibrillation-with-rapid-ventricular-response-in-the-intensive-care-unit-a-secondary-analysis-of-electronic-health-record-data
#19
Ari Moskowitz, Kenneth P Chen, Avraham Z Cooper, Abdullah Chahin, Mohammad M Ghassemi, Leo Anthony Celi
PURPOSE: Atrial fibrillation with rapid ventricular response (RVR) is common during critical illness. In this study, we explore the comparative effectiveness of three commonly used drugs (metoprolol, diltiazem, and amiodarone) in the management of atrial fibrillation with RVR in the intensive care unit (ICU). METHODS: Data pertaining to the first ICU admission were extracted from the Medical Information Mart for Intensive Care (MIMIC) III database. Patients who received one of the above pharmacologic agents while their heart rate was > 110bpm and had atrial fibrillation documented in the clinical chart were included...
March 21, 2017: Shock
https://www.readbyqxmd.com/read/28328523/real-life-dabigatran-and-metabolite-concentrations-focused-on-inter-patient-variability-and-assay-differences-in-patients-with-atrial-fibrillation
#20
Kristel Boonen, Ellen Schmitz, Fleur Rozestraten, Dennis van den Heuvel, Luc Brunsveld, Pepijn van der Voort, Daan van de Kerkhof
BACKGROUND: Dabigatran is prescribed to increasing numbers of patients with atrial fibrillation (AF). Although routine monitoring is not considered to be useful, measuring drug concentrations can be clinically relevant in specific situations. The aim of this study was the comparison of different functional and non-functional assays for determination of dabigatran concentrations at different timepoints in a real-life patient population with AF. We focused on the differences between assays in identifying patients with low drug concentrations...
March 22, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
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