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https://www.readbyqxmd.com/read/29786857/effect-of-oatp1b1-1b3-inhibitor-gdc-0810-on-the-pharmacokinetics-of-pravastatin-and-coproporphyrin-i-iii-in-healthy-female-subjects
#1
Lichuan Liu, Sravanthi Cheeti, Kenta Yoshida, Edna Choo, Eugene Chen, Buyun Chen, Mary Gates, Stina Singel, Roland Morley, Joseph Ware, Srikumar Sahasranaman
Developed as an oral anticancer drug to treat estrogen receptor-positive breast cancer, GDC-0810 was shown to be a potent inhibitor of organic anion-transporting polypeptide 1B1 and 1B3 (OATP1B1/1B3) from an in vitro assay. A clinical study was conducted to assess the drug-drug interaction potential between GDC-0810 and pravastatin, which is a relatively selective and sensitive OATP1B1/1B3 substrate. Fifteen healthy female subjects of non-childbearing potential were enrolled in the study. On day 1 in period 1, a single 10-mg dose of pravastatin was administered to all subjects...
May 22, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29786712/cocrystals-of-a-1-2-4-thiadiazole-based-potent-neuroprotector-with-gallic-acid-solubility-thermodynamic-stability-relationships-and-formation-pathways
#2
Artem O Surov, Andrei V Churakov, Alexey N Proshin, Xia-Lin Dai, Tongbu Lu, German L Perlovich
Three distinct solid forms, namely anhydrous cocrystals with 2 : 1 and 1 : 1 drug/acid ratios ([TDZ : GA] (2 : 1), [TDZ : GA] (1 : 1)), and a hydrated one having 1 : 1 : 1 drug/acid/water stoichiometry ([TDZ : GA : H2O] (1 : 1 : 1)), have been formed by cocrystallization of the biologically active 1,2,4-thiadiazole derivative (TDZ) with gallic acid (GA). The thermodynamic stability relationships between the cocrystals were rationalized in terms of Gibbs energies of the formation reactions and further verified by performing a set of competitive and exchange mechanochemical reactions...
May 22, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29785580/a-comprehensive-review-and-meta-analysis-of-risk-factors-for-statin-induced-myopathy
#3
REVIEW
Khoa A Nguyen, Lang Li, Deshun Lu, Aida Yazdanparast, Lei Wang, Rolf P Kreutz, Elizabeth C Whipple, Titus K Schleyer
PURPOSE: To aid prescribers in assessing a patient's risk for statin-induced myopathy (SIM), we performed a comprehensive review of currently known risk factors and calculated aggregated odds ratios for each risk factor through a meta-analysis. METHODS: This meta-analysis was done through four phases: (1) Identification of the relevant primary literature; (2) abstract screening using inclusion and exclusion criteria; (3) detailed review and data extraction; and (4) synthesis and statistical analysis...
May 22, 2018: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29785435/assessing-the-performance-of-mm-pbsa-and-mm-gbsa-methods-7-entropy-effects-on-the-performance-of-end-point-binding-free-energy-calculation-approaches
#4
Huiyong Sun, Lili Duan, Fu Chen, Hui Liu, Zhe Wang, Peichen Pan, Feng Zhu, John Z H Zhang, Tingjun Hou
Entropy effects play an important role in drug-target interactions, but the entropic contribution to ligand-binding affinity is often neglected by end-point binding free energy calculation methods, such as MM/GBSA and MM/PBSA, due to the expensive computational cost of normal mode analysis (NMA). Here, we systematically investigated entropy effects on the prediction power of MM/GBSA and MM/PBSA using >1500 protein-ligand systems and six representative AMBER force fields. Two computationally efficient methods, including NMA based on truncated structures and the interaction entropy approach, were used to estimate the entropic contributions to ligand-target binding free energies...
May 22, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29785088/insight-into-resistance-mechanism-of-anaplastic-lymphoma-kinase-to-alectinib-and-jh-viii-157-02-caused-by-g1202r-solvent-front-mutation
#5
Han Wang, Yao Wang, Wentao Guo, Bin Du, Xiaobing Huang, Riping Wu, Baoyu Yang, Xiaoyan Lin, Yilan Wu
Background: Mutated anaplastic lymphoma kinase (ALK) drives the development of advanced non-small cell lung cancer (NSCLC). Most reported small-molecule inhibitors targeting the ALK domain do not display good inhibition of the G1202R solvent front mutation. The solvent front mutation was assumed to hinder drug binding. However, a different fact could be uncovered by the simulations reported in this study through a structural analog of alectinib (JH-VIII-157-02), which demonstrated potent effects against the G1202R mutation...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29784546/complexity-of-the-medication-regimen-for-polypathological-patients
#6
L Bellostas-Muñoz, J Díez-Manglano
OBJECTIVE: To determine the complexity of the therapeutic regimen for polypathological patients hospitalised in internal medicine departments. METHODS: A multicentre observational study included polypathological patients hospitalised in internal medicine departments. Patients who were readmitted or died were excluded. Data were collected on age, sex, residence, disease, Charlson, Barthel and Lawton-Brody indices, Pfeiffer questionnaire, Gijón scale, number of hospitalisations in the previous year, delirium, need for and availability of caregivers and the PROFUND index score...
May 18, 2018: Revista Clínica Española
https://www.readbyqxmd.com/read/29784372/fast-and-reliable-bia-amperometric-quantification-of-acetylcysteine-using-a-nanostructured-double-hydroxide-sensor
#7
Anabel Laza Correa, Josué M Gonçalves, Pamela O Rossini, Juliana S Bernardes, Carlos A Neves, Koiti Araki, Lucio Angnes
This study reports the preparation and characterization of nickel/lead hydroxide nanoparticles used to construct electrochemical sensors, which were investigated for amperometric quantification of N-acetylcysteine (NAC). The newly synthesised material presents good uniformity, with the lead (II) ions homogenously incorporated into the alpha nickel hydroxide crystal structure, confirmed by X-ray diffraction, transmission electron microscopy and X-ray photoelectron spectroscopy analyses. Films of nanoparticles (3 nm in size) were prepared on conductive fluorine-doped tin oxide-coated glass slides and used connected to a specially built batch injection analysis (BIA) cell with a capacity of only 4 mL and the electrode positioned in the bottom...
August 15, 2018: Talanta
https://www.readbyqxmd.com/read/29784276/associations-of-drug-use-violence-and-depressive-symptoms-with-sexual-risk-behaviors-among-women-with-alcohol-misuse
#8
Kristen Lee, Heidi E Hutton, Catherine R Lesko, Anne K Monroe, Anika Alvanzo, Mary E McCaul, Geetanjali Chander
BACKGROUND: Alcohol misuse is associated with increased human immunodeficiency virus sexual risk behaviors by women. Drug use, intimate partner violence (IPV), and depressive symptoms frequently co-occur, are well-recognized alcohol misuse comorbidities, and may interact to increase risk behaviors. Using a syndemic framework we examined associations between drug use, IPV, and depressive symptoms and sexual risk behaviors by 400 women with alcohol misuse attending an urban sexually transmitted infections clinic...
May 18, 2018: Women's Health Issues: Official Publication of the Jacobs Institute of Women's Health
https://www.readbyqxmd.com/read/29783113/automated-uhplc-separation-of-10-pharmaceutical-compounds-using-software-modeling
#9
A Zöldhegyi, H-J Rieger, I Molnár, L Fekhretdinova
Human mistakes are still one of the main reasons of underlying regulatory affairs that in a compliance with FDA's Data Integrity and Analytical Quality by Design (AQbD) must be eliminated. To develop smooth, fast and robust methods that are free of human failures, a state-of-the-art automation was presented. For the scope of this study, a commercial software (DryLab) and a model mixture of 10 drugs were subjected to testing. Following AQbD-principles, the best available working point was selected and conformational experimental runs, i...
March 20, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29782910/comparison-of-dissolution-time-profiles-no-similarity-but-where-is-the-difference
#10
Stefan Horkovics-Kovats
The similarity of the dissolution time profiles is routinely determined by various statistical methods, e.g. by calculating the f2 similarity factor, by calculating the multivariate statistical distance or determining the confidence interval of f2 metrics using the bootstrapping method. If the similarity of the dissolution profiles is not achieved, these methods provide no information about the possible causes of the differences in the final dosage forms. In this article it is shown that after introduction of summary parameters into the disintegration-dissolution model (DDM), such as intrinsic lifetime distribution of particles, saturation state function, drug load of the system and applying population data analysis, differences on the level of intrinsic lifetime distributions of particles of active pharmaceutical ingredient in immediately release formulations are identified...
May 18, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29782862/evaluation-of-cardiac-arrhythmic-risks-using-a-rabbit-model-of-left-ventricular-systolic-dysfunction
#11
Bianca Hemmeryckx, Yuanbo Feng, Liesbeth Frederix, Marleen Lox, Sander Trenson, Rob Vreeken, Hua Rong Lu, David Gallacher, Yicheng Ni, H Roger Lijnen
Patients with heart disease have a higher risk to develop cardiac arrhythmias, either spontaneously or drug-induced. In this study, we have used a rabbit model of myocardial infarction (MI) with severe left ventricular systolic dysfunction (LVSD) to study potential drug-induced cardiac risks with N-(piperidin-2-ylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide (flecainide). Upon ligation of the left circumflex arteries, male New Zealand White rabbits developed a large MI and moderate or severe LVSD 7 weeks after surgery, in comparison to SHAM-operated animals...
May 18, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29782388/glasgow-coma-scale-score-fluctuations-are-inversely-associated-with-a-nirs-based-index-of-cerebral-autoregulation-in-acutely-comatose-patients
#12
Ryan J Healy, Andres Zorrilla-Vaca, Wendy Ziai, Marek A Mirski, Charles W Hogue, Romergryko Geocadin, Batya Radzik, Caitlin Palmisano, Lucia Rivera-Lara
BACKGROUND: The Glasgow Coma Scale (GCS) is an essential coma scale in critical care for determining the neurological status of patients and for estimating their long-term prognosis. Similarly, cerebral autoregulation (CA) monitoring has shown to be an accurate technique for predicting clinical outcomes. However, little is known about the relationship between CA measurements and GCS scores among neurological critically ill patients. This study aimed to explore the association between noninvasive CA multimodal monitoring measurements and GCS scores...
May 18, 2018: Journal of Neurosurgical Anesthesiology
https://www.readbyqxmd.com/read/29782180/current-evidence-on-heart-rate-variability-biofeedback-as-a-complementary-anticraving-intervention
#13
Nour Alayan, Lucille Eller, Marsha E Bates, Dennis P Carmody
BACKGROUND: The limited success of conventional anticraving interventions encourages research into new treatment strategies. Heart rate variability biofeedback (HRVB), which is based on slowed breathing, was shown to improve symptom severity in various disorders. HRVB, and certain rates of controlled breathing (CB), may offer therapeutic potential as a complementary drug-free treatment option to help control substance craving. METHODS: This review evaluated current evidence on the effectiveness of HRVB and CB training as a complementary anticraving intervention, based on guidelines from the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols...
May 21, 2018: Journal of Alternative and Complementary Medicine: Research on Paradigm, Practice, and Policy
https://www.readbyqxmd.com/read/29782045/revisiting-the-table-2-fallacy-a-motivating-example-examining-preeclampsia-and-preterm-birth
#14
Gretchen Bandoli, Kristin Palmsten, Christina D Chambers, Laura L Jelliffe-Pawlowski, Rebecca J Baer, Caroline A Thompson
BACKGROUND: A "Table Fallacy," as coined by Westreich and Greenland, reports multiple adjusted effect estimates from a single model. This practice, which remains common in published literature, can be problematic when different types of effect estimates are presented together in a single table. The purpose of this paper is to quantitatively illustrate this potential for misinterpretation with an example estimating the effects of preeclampsia on preterm birth. METHODS: We analysed a retrospective population-based cohort of 2 963 888 singleton births in California between 2007 and 2012...
May 21, 2018: Paediatric and Perinatal Epidemiology
https://www.readbyqxmd.com/read/29780352/the-nomogram-of-penile-length-and-circumference-in-iranian-term-and-preterm-neonates
#15
Fahimeh Soheilipour, Farzaneh Rohani, Elham Hashemi Dehkordi, Roya Isa Tafreshi, Parisa Mohagheghi, Seyed-Mohammadsalar Zaheriani, Fatemeh Jesmi, Hamid Salehiniya
Background and objectives: The normal length of penis in preterm and term neonates is different among different nations, and is affected by various factors. The present study aimed to determine stretched penile length (SPL) values and cutoff level of micropenis in term and preterm Iranian neonates, for the first time. Materials and methods: All male neonates born in two general hospitals of Tehran (Akbarabadi, and Rasoul hospitals), center of Iran, with gestational age of 28-42 weeks were included and their SPL and penile circumference (PC) were examined on the first 3 days after birth by the same physician...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29780330/application-of-feedback-system-control-optimization-technique-in-combined-use-of-dual-antiplatelet-therapy-and-herbal-medicines
#16
Wang Liu, Yu-Long Li, Mu-Ting Feng, Yu-Wei Zhao, Xianting Ding, Ben He, Xuan Liu
Aim: Combined use of herbal medicines in patients underwent dual antiplatelet therapy (DAPT) might cause bleeding or thrombosis because herbal medicines with anti-platelet activities may exhibit interactions with DAPT. In this study, we tried to use a feedback system control (FSC) optimization technique to optimize dose strategy and clarify possible interactions in combined use of DAPT and herbal medicines. Methods: Herbal medicines with reported anti-platelet activities were selected by searching related references in Pubmed...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29779958/development-of-an-anti-epo-antibody-detection-kit-based-on-lab-on-a-chip-and-bridging-antibody-technologies
#17
Jin-Gyo Oh, Jihyun Seong, Sunmi Han, Tae-Hwe Heo
Immunogenicity is a major concern in the use of biological drugs. In particular, antibody-mediated pure red cell aplasia (PRCA) is a rare condition that is caused by administration of recombinant erythropoietin. There are numerous assay platforms for detect EPO anti-drug antibody (ADA), and most have appropriate assay sensitivity, but in need of improvement in terms of assay turnaround time and user accessibility. Here, the new method was developed based on lab-on-a-chip technology and bridging ELISA. The FREND™ Cartridge is equipped with a microfluidic lateral flow channel, enabling easy, fast and accurate immunoassays with small sample volumes...
May 17, 2018: Biologicals: Journal of the International Association of Biological Standardization
https://www.readbyqxmd.com/read/29779917/antimicrobial-resistance-among-migrants-in-europe-a-systematic-review-and-meta-analysis
#18
Laura B Nellums, Hayley Thompson, Alison Holmes, Enrique Castro-Sánchez, Jonathan A Otter, Marie Norredam, Jon S Friedland, Sally Hargreaves
BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings...
May 17, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29779485/tgn-1412-and-bia-2474-trials-with-tragic-end-lessons-learnt-to-make-clinical-trials-safer
#19
Rimple Jeet Kaur, Surjit Singh, Preeti Sidhu, Pramod Kumar Sharma
BACKGROUND: Globally, there have been tremendous efforts by regulatory authorities to make clinical trials safer by making stringent clinical trial regulations. Despite this, we witnessed several tragic events. TGN1412 and BIA 10-2474 phase I trials are infamous trails in which healthy volunteers either succumbed to severe adverse effects or faced irreversible impairments of the test drug. Such afflictions in clinical trials are not only turbulent to the image of pharmaceutical industry but it also conveys dispiriting message for clinical trial participants...
May 20, 2018: Reviews on Recent Clinical Trials
https://www.readbyqxmd.com/read/29778887/biological-potential-of-oxo-vanadium-salicylediene-amino-acid-complexes-as-cytotoxic-antimicrobial-antioxidant-and-dna-interaction
#20
Mohamed Shaker S Adam, Hany Elsawy
New series of oxo-vanadium N-salicyledieneamino acid Schiff base complexes are synthesized and characterized. They are synthesized from the reaction of sodium salicylaldehyde-5-sulfonate, some amino acids, alanine (VOHL1), leucine (VOHL2) or glycine (VOHL3) in an aqueous media, and leucine (VOHLpy1) or tryptophan (VOHLpy2) in pyridine with vanadyl acetylacetonate. The complexes are characterized by EA, TGA, IR, UV-Visible and mass spectra, conductivity and magnetic measurements. The biological activity of the VO-complexes shows that VOHL1, VOHL2 and VOHL3 exhibit anti-proliferative effect and may be used as anticancer drugs...
May 4, 2018: Journal of Photochemistry and Photobiology. B, Biology
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