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https://www.readbyqxmd.com/read/27914088/murine-mycobacterium-marinum-infection-as-a-model-for-tuberculosis
#1
Julia Lienard, Fredric Carlsson
Mycobacteria are a major human health problem globally. Regarding tuberculosis the situation is worsened by the poor efficacy of current vaccine regimens and by emergence of drug-resistant strains (Manjelievskaia J et al, Trans R Soc Trop Med Hyg 110: 110, 2016; Pereira et al., Lancet Infect Dis 12:300-306, 2012; http://www.who.int/tb/publications/global_report/en/) undermining both disease-prevention and available treatments. Thus, increased basic understanding of mycobacterial-and particularly Mycobacterium tuberculosis-virulence strategies and pathogenesis is of great importance...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27913813/-rehabilitation-after-hip-and-knee-endoprosthetic-treatment-in-the-elderly
#2
H Bork
Due to current demographic developments with a continuous increase in average life expectancy and improved medical treatment, the number of elderly patients with joint replacement of the lower extremities also has increased in recent years. Most of these patients have not only one but several chronic diseases requiring treatment and medication. Drug-drug interaction and functional restrictions of the elderly additionally reduce the postoperative psychophysical capacity; therefore, special knowledge in rehabilitative treatment and pain management is necessary...
December 2, 2016: Der Orthopäde
https://www.readbyqxmd.com/read/27913252/sex-and-gender-differences-in-the-treatment-of-alzheimer-s-disease-a-systematic-review-of-randomized-controlled-trials
#3
Marco Canevelli, Federica Quarata, Francesca Remiddi, Flaminia Lucchini, Eleonora Lacorte, Nicola Vanacore, Giuseppe Bruno, Matteo Cesari
In recent years, epidemiological, clinical, and biological evidence has drawn the attention on the influence of sex and gender on Alzheimer's disease (AD). Nevertheless, not enough attention has been paid to their impact on treatment outcomes. The present study is aimed at systematically retrieve, review and discuss data coming from available randomized placebo-controlled trials (RCTs) on currently marketed treatments for AD (i.e., cholinesterase inhibitors [ChEIs] and memantine) in order to describe possible sex and gender differences in their efficacy, safety and tolerability...
November 29, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27913149/mutations-at-protein-protein-interfaces-small-changes-over-big-surfaces-have-large-impacts-on-human-health
#4
REVIEW
Harry C Jubb, Arun P Pandurangan, Meghan A Turner, Bernardo Ochoa-Montaño, Tom L Blundell, David B Ascher
Many essential biological processes including cell regulation and signalling are mediated through the assembly of protein complexes. Changes to protein-protein interaction (PPI) interfaces can affect the formation of multiprotein complexes, and consequently lead to disruptions in interconnected networks of PPIs within and between cells, further leading to phenotypic changes as functional interactions are created or disrupted. Mutations altering PPIs have been linked to the development of genetic diseases including cancer and rare Mendelian diseases, and to the development of drug resistance...
November 29, 2016: Progress in Biophysics and Molecular Biology
https://www.readbyqxmd.com/read/27912908/childhood-sexual-abuse-and-substance-abuse-a-gender-paradox
#5
Lil Tonmyr, Margot Shields
We examine associations between childhood sexual abuse (CSA) and substance abuse, the role of mental health indicators as mediators in these associations and whether or not associations differ by gender. Data are from 14,063 respondents aged 18-76 years from the 2004-2005 Canadian Gender, Alcohol, and Culture: An International Study (GENACIS). Multiple logistic regression models were used to examine associations between CSA and substance abuse variables, controlling for socio-demographic factors. Odds were adjusted by indicators of mental health to assess if these variables mediated associations between CSA and substance abuse...
November 29, 2016: Child Abuse & Neglect
https://www.readbyqxmd.com/read/27911829/supramolecular-pegylation-of-biopharmaceuticals
#6
Matthew J Webber, Eric A Appel, Brittany Vinciguerra, Abel B Cortinas, Lavanya S Thapa, Siddharth Jhunjhunwala, Lyle Isaacs, Robert Langer, Daniel G Anderson
The covalent modification of therapeutic biomolecules has been broadly explored, leading to a number of clinically approved modified protein drugs. These modifications are typically intended to address challenges arising in biopharmaceutical practice by promoting improved stability and shelf life of therapeutic proteins in formulation, or modifying pharmacokinetics in the body. Toward these objectives, covalent modification with poly(ethylene glycol) (PEG) has been a common direction. Here, a platform approach to biopharmaceutical modification is described that relies on noncovalent, supramolecular host-guest interactions to endow proteins with prosthetic functionality...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911825/elucidating-the-druggable-interface-of-protein-protein-interactions-using-fragment-docking-and-coevolutionary-analysis
#7
Fang Bai, Faruck Morcos, Ryan R Cheng, Hualiang Jiang, José N Onuchic
Protein-protein interactions play a central role in cellular function. Improving the understanding of complex formation has many practical applications, including the rational design of new therapeutic agents and the mechanisms governing signal transduction networks. The generally large, flat, and relatively featureless binding sites of protein complexes pose many challenges for drug design. Fragment docking and direct coupling analysis are used in an integrated computational method to estimate druggable protein-protein interfaces...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911475/carboplatin-complexed-and-crgd-conjugated-unimolecular-nanoparticles-for-targeted-ovarian-cancer-therapy
#8
Yuyuan Wang, Liwei Wang, Guojun Chen, Shaoqin Gong
Platinum-based chemotherapy has been widely used to treat cancers including ovarian cancer; however, it suffers from dose-limiting toxicity. Judiciously designed drug nanocarriers can enhance the anticancer efficacy of platinum-based chemotherapy while reducing its systemic toxicity. Herein the authors report a stable and water-soluble unimolecular nanoparticle constructed from a hydrophilic multi-arm star block copolymer poly(amidoamine)-b-poly(aspartic acid)-b-poly(ethylene glycol) (PAMAM-PAsp-PEG) conjugated with both cRGD (cyclo(Arg-Gly-Asp-D-Phe-Cys) peptide and cyanine5 (Cy5) fluorescent dye as a platinum-based drug nanocarrier for targeted ovarian cancer therapy...
December 1, 2016: Macromolecular Bioscience
https://www.readbyqxmd.com/read/27911294/deleterious-effect-of-butyrylcholinesterase-k-variant-in-donepezil-treatment-of-mild-cognitive-impairment
#9
Sophie Sokolow, Xiaohui Li, Lucia Chen, Kent D Taylor, Jerome I Rotter, Robert A Rissman, Paul S Aisen, Liana G Apostolova
BACKGROUND: Donepezil is an acetylcholinesterase inhibitor frequently prescribed for the treatment of mild cognitive impairment (MCI) though not approved by the Food and Drug Administration for this indication. In Alzheimer's disease, butyrylcholinesterase (BChE) activity increases with disease progression and may replace acetylcholinesterase function. The most frequent polymorphism of BChE is the K-variant, which is associated with lower acetylcholine-hydrolyzing activity. BChE-K polymorphism has been studied in Alzheimer's disease progression and donepezil therapy, and has led to contradictory results...
November 29, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27911223/advances-in-capillary-electrophoresis-and-the-implications-for-drug-discovery
#10
Claire M Ouimet, Cara I D'Amico, Robert T Kennedy
Many screening platforms are prone to assay interferences that can be avoided by directly measuring the target or enzymatic product. Capillary electrophoresis (CE) and microchip electrophoresis (MCE) have been applied in a variety of formats to drug discovery. CE provides direct detection of the product allowing for the identification of some forms of assay interference. The high efficiency, rapid separations, and low volume requirements make CE amenable to drug discovery. Areas Covered: This article describes advances in capillary electrophoresis throughput, sample introduction, and target assays as they pertain to drug discovery and screening...
December 2, 2016: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/27910990/a-ph-responsive-sequential-disassembly-nanohybrid-for-mitochondrial-targeting
#11
Lijia Li, Wei Sun, Lian Li, Yuanyuan Liu, Lei Wu, Fengling Wang, Zhou Zhou, Zhirong Zhang, Yuan Huang
Cationic materials have been reported as promising tools for targeting to mitochondria which are the "power houses" and "metabolic garbage keepers" of cells. However, their positive nature also restricts their in vivo application due to the quick clearance. Herein, we fabricated a nanohybrid consisting of the pH-responsive N-(2-hydroxypropyl)methacrylamide (HPMA) co-polymer (R-P) shells and positive mesoporous silica nanoparticle cores via electrostatic interaction. The anticancer drug, docetaxel (DTX), was encapsulated in the positive MSN cores (MSN-DTX)...
December 2, 2016: Nanoscale
https://www.readbyqxmd.com/read/27910732/binding-of-anti-cardiovascular-drug-to-serum-albumin-an-insight-in-the-light-of-spectroscopic-and-computational-approaches
#12
Tajalli Ilm Chandel, Gulam Rabbani, MohsinVahid Khan, Masihuz Zaman, Parvez Alam, Yasser Shahein, Rizwan Hasan Khan
Isoprenaline hydrochloride is a potential cardiovascular drug helps in the smooth functioning of the heart muscles. So, we have performed the binding study of ISO with BSA. This study was investigated by UV absorption, fluorescence, synchronous fluorescence, circular dichroism etc. The analysis of intrinsic fluorescence data showed the low binding affinity of ISO. The binding constant Kb was 2.8×103 M-1 and binding stoichiometry (n) was approximately one and the Gibb's free energy change at 310 K was determined to be -8...
December 2, 2016: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/27910730/retrospective-use-of-pbpk-modelling-to-understand-a-clinical-drug-drug-interaction-between-dextromethorphan-and-gsk1034702
#13
Michael J Hobbs, Jackie Bloomer, Gordon Dear
: 1. PURPOSE: In a clinical trial, a strong drug-drug interaction (DDI) was observed between dextromethorphan (DM, the object or victim drug) and GSK1034702 (the precipitant or perpetrator drug), following single and repeat doses. This study determined the inhibition parameters of GSK1034702 in vitro and applied PBPK modelling approaches to simulate the clinical observations and provide mechanistic hypotheses to understand the DDI. 2. METHODS: In vitro assays were conducted to determine the inhibition parameters of human CYP2D6 by GSK1034702...
December 2, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27910729/identification-of-cytochrome-p450s-involved-in-the-metabolism-of-6-benzyl-1-benzyloxymethyl-5-iodouracil-w-1-using-human-recombinant-enzymes-and-rat-liver-microsomes-in-vitro
#14
Ying-Yuan Lu, Hai-Xu Cheng, Xin Wang, Xiao-Wei Wang, Jun-Yi Liu, Pu Li, Ya-Qing Lou, Jun Li, Chuang Lu, Guo-Liang Zhang
1. The aim of this study was to identify the hepatic metabolic enzymes, which involved in the biotransformation of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W-1), a novel non-nucleoside reverse transcriptase inhibitor (NNRTIs) in rat and human in vitro. 2. The parent drug of W-1 was incubated with RLMs or recombinant CYPs (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5, respectively) in the presence or absence of NADPH regenerating system. The metabolites of W-1 were analyzed with liquid chromatography-ion trap-time of flight-mass spectrometry (LC-IT-TOF-MS)...
December 2, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/27910713/sn-38-loading-capacity-of-hydrophobic-polymer-blend-nanoparticles-formulation-optimization-and-efficacy-evaluation
#15
Simona Dimchevska, Nikola Geskovski, Gjorgji Petruševski, Marina Chacorovska, Riste Popeski-Dimovski, Sonja Ugarkovic, Katerina Goracinova
One of the most important problems in nanoencapsulation of extremely hydrophobic drugs is poor drug loading due to rapid drug crystallization outside the polymer core. The effort to use nanoprecipitation, as a simple one-step procedure with good reproducibility and FDA approved polymers like Poly(lactic-co-glycolic acid) (PLGA) and Polycaprolactone (PCL), will only potentiate this issue. Considering that drug loading is one of the key defining characteristics, in this study we attempted to examine whether the nanoparticle core composed of two hydrophobic polymers will provide increased drug loading for 7-Ethyl-10-hydroxy-camptothecin (SN-38), relative to nanoparticles prepared using individual polymers...
December 2, 2016: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/27909995/solithromycin-a-novel-fluoroketolide-for-the-treatment-of-community-acquired-bacterial-pneumonia
#16
REVIEW
George G Zhanel, Erika Hartel, Heather Adam, Sheryl Zelenitsky, Michael A Zhanel, Alyssa Golden, Frank Schweizer, Bala Gorityala, Philippe R S Lagacé-Wiens, Andrew J Walkty, Alfred S Gin, Daryl J Hoban, Joseph P Lynch, James A Karlowsky
Solithromycin is a novel fluoroketolide developed in both oral and intravenous formulations to address increasing macrolide resistance in pathogens causing community-acquired bacterial pneumonia (CABP). When compared with its macrolide and ketolide predecessors, solithromycin has several structural modifications which increase its ribosomal binding and reduce its propensity to known macrolide resistance mechanisms. Solithromycin, like telithromycin, affects 50S ribosomal subunit formation and function, as well as causing frame-shift errors during translation...
December 1, 2016: Drugs
https://www.readbyqxmd.com/read/27909711/effect-of-partial-pegylation-on-particle-uptake-by-macrophages
#17
Lucero Sanchez, Yi Yi, Yan Yu
Controlling the internalization of synthetic particles by immune cells remains a grand challenge for developing successful drug carrier systems. Polyethylene glycol (PEG) is frequently used as a protective coating on particles to evade immune clearance, but it also hinders the interactions of particles with their intended target cells. In this study, we investigate a spatial decoupling strategy, in which PEGs are coated on only one hemisphere of particles, so that the other hemisphere is available for functionalization of cell-targeting ligands without the hindrance effect from the PEGs...
December 2, 2016: Nanoscale
https://www.readbyqxmd.com/read/27909650/pbpk-modeling-and-simulation-in-drug-research-and-development
#18
REVIEW
Xiaomei Zhuang, Chuang Lu
Physiologically based pharmacokinetic (PBPK) modeling and simulation can be used to predict the pharmacokinetic behavior of drugs in humans using preclinical data. It can also explore the effects of various physiologic parameters such as age, ethnicity, or disease status on human pharmacokinetics, as well as guide dose and dose regiment selection and aid drug-drug interaction risk assessment. PBPK modeling has developed rapidly in the last decade within both the field of academia and the pharmaceutical industry, and has become an integral tool in drug discovery and development...
September 2016: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/27909544/reducing-the-risk-of-stroke-in-patients-with-nonvalvular-atrial-fibrillation-with-direct-oral-anticoagulants-is-one-of-these-not-like-the-others
#19
REVIEW
Paul P Dobesh Pharm D, John Fanikos Mba R Ph
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and increases risk of stroke by nearly 5-fold. While warfarin has been employed successfully to reduce the risk of stroke in these patients, there are a number of challenges with therapy. These include the need for therapeutic monitoring due to variability in patient response, frequent dose adjustments, numerous drug-drug, drug-food, and drug-disease interactions, and a heightened risk of thrombosis and bleeding due to these issues. Current guidelines recommend that the vitamin K antagonists (VKA) or direct oral anticoagulants (DOACs) should be used for thromboprophylaxis in patients with nonvalvular AF at risk for stroke or systemic embolic events...
August 2016: Journal of Atrial Fibrillation
https://www.readbyqxmd.com/read/27909372/knowledge-and-use-of-and-attitudes-toward-non-steroidal-anti-inflammatory-drugs-nsaids-in-practice-a-survey-of-ontario-physiotherapists
#20
Maggie Green, Kathleen E Norman
Purpose: To investigate Ontario physiotherapists' knowledge and use of, and attitudes toward, non-steroidal anti-inflammatory drugs (NSAIDs) to identify whether there is a need for physiotherapists to receive education specific to NSAIDs. Method: An existing survey instrument was modified and tested by five Ontario physiotherapists. The final version was distributed electronically to approximately 4,400 Ontario Physiotherapy Association members as a self-administered online questionnaire. Results: A total of 294 physiotherapists responded to the survey (response rate=6...
2016: Physiotherapy Canada. Physiothérapie Canada
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