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https://www.readbyqxmd.com/read/28817561/comparing-efficacies-of-moxifloxacin-levofloxacin-and-gatifloxacin-in-tuberculosis-granulomas-using-a-multi-scale-systems-pharmacology-approach
#1
Elsje Pienaar, Jansy Sarathy, Brendan Prideaux, Jillian Dietzold, Véronique Dartois, Denise E Kirschner, Jennifer J Linderman
Granulomas are complex lung lesions that are the hallmark of tuberculosis (TB). Understanding antibiotic dynamics within lung granulomas will be vital to improving and shortening the long course of TB treatment. Three fluoroquinolones (FQs) are commonly prescribed as part of multi-drug resistant TB therapy: moxifloxacin (MXF), levofloxacin (LVX) or gatifloxacin (GFX). To date, insufficient data are available to support selection of one FQ over another, or to show that these drugs are clinically equivalent. To predict the efficacy of MXF, LVX and GFX at a single granuloma level, we integrate computational modeling with experimental datasets into a single mechanistic framework, GranSim...
August 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28817244/key-developments-that-impacted-the-field-of-mechanobiology-and-mechanotransduction
#2
Michelle Wall, David Butler, Alicia El Haj, Josephine C Bodle, Elizabeth G Loboa, Albert J Banes
Advances in mechanobiology have evolved through insights from multiple disciplines including structural engineering, biomechanics, vascular biology, and orthopaedics. In this paper, we reviewed the impact of key reports related to the study of applied loads on tissues and cells and the resulting signal transduction pathways. We addressed how technology has helped advance the burgeoning field of mechanobiology (over 33,600 publications from 1970-2016). We analyzed the impact of critical ideas and then determined how these concepts influenced the mechanobiology field by looking at the citation frequency of these reports as well as tracking how the overall number of citations within the field changed over time...
August 17, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28816643/pharmacometabolomics-informs-quantitative-radiomics-for-glioblastoma-diagnostic-innovation
#3
Theodora Katsila, Minos-Timotheos Matsoukas, George P Patrinos, Dimitrios Kardamakis
Applications of omics systems biology technologies have enormous promise for radiology and diagnostics in surgical fields. In this context, the emerging fields of radiomics (a systems scale approach to radiology using a host of technologies, including omics) and pharmacometabolomics (use of metabolomics for patient and disease stratification and guiding precision medicine) offer much synergy for diagnostic innovation in surgery, particularly in neurosurgery. This synthesis of omics fields and applications is timely because diagnostic accuracy in central nervous system tumors still challenges decision-making...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28816386/chemotaxis-guided-hybrid-neutrophil-micromotor-for-actively-targeted-drug-transport
#4
Jingxin Shao, Mingjun Xuan, Hongyue Zhang, Xiankun Lin, Zhiguang Wu, Qiang He
Engineering self-propelled micromotors with good biocompatibility and biodegradability for actively seeking sites of diseases and targeted drug transport remains a huge challenge. Here we demonstrate that neutrophils with intrinsic chemotaxis ability could be transformed into self-guided biohybrid motors through integrating mesoporous silica nanoparticles (MSNs) with high loading capability. To realize the compatibility of neutrophil cells with drug-loaded MSNs, bacteria membranes derived from E. coli were coated onto MSNs in advance by using a camouflaging strategy...
August 17, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28816051/lipid-stabilized-water-oil-interfaces-studied-by-micro-focusing-small-angle-x-ray-scattering
#5
Emanuela Di Cola, Kristian Torbensen, Ilaria Clemente, Federico Rossi, Sandra Ristori, Ali Abou-Hassan
Water in oil (w/o) simple emulsions are dispersed micro-confined systems which find applications in many areas of advanced materials and biotechnology, such as food industry, drug delivery and cosmetics, to name but a few. In these systems, the structural and chemical properties of the boundary layer at the w/o interface are of paramount importance to determine functionality and stability. Recently, microfluidic methods have emerged as a valuable tool to fabricate monodisperse emulsion droplets. Due to the intrinsic flexibility of microfluidics, different interfaces can be obtained, and general principles governing the interfacial stability are needed to guide the experimental approach...
August 17, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28816016/the-discovery-of-new-and-more-potent-chloropyramine-c4-analogues-for-the-potential-treatment-of-invasive-breast-cancer
#6
Sahar Kandil, Filippo Prencipe, Samuel Jones, Stephen Hiscox, Andrew D Westwell
Breast cancer (BC) is the second most common cancer worldwide, accounting for 25% of all female cancers. Although the survival rate has increased significantly in the past few decades, patients who develop secondary site metastasis as well as those diagnosed with triple negative breast cancer (TNBC) still represent a real unmet medical challenge. Previous studies have shown that chloropyramine (C4) inhibits FAK-VEGFR3 signaling. More recently, C4 is reported to have SASH1 inducing properties. However, C4 exerts its antitumour and antiangiogenic effects at high micromolar concentrations (>100 μM) that would not be compatible with further drug development against invasive breast cancer driven by FAK signaling...
August 16, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28815921/structure-modification-toward-applicability-domain-of-a-qsar-qspr-model-considering-activity-property
#7
Shoki Ochi, Tomoyuki Miyao, Kimito Funatsu
In drug and material design, the activity and property values of the designed chemical structures can be predicted by quantitative structure-activity and structure-property relationship (QSAR/QSPR) models. When a QSAR/QSPR model is applied to chemical structures, its applicability domain (AD) must be considered. The predicted activity/property values are only reliable for chemical structures inside the AD. Chemical structures outside the AD are usually neglected, as the predicted values are unreliable. The purpose of this study is to develop a methodology for obtaining novel chemical structures with the desired activity or property based on a QSAR/QSPR model by making use of the neglected structures...
August 16, 2017: Molecular Informatics
https://www.readbyqxmd.com/read/28815830/determinants-of-the-inhibition-of-dpre1-and-cyp2c9-by-antitubercular-thiophenes
#8
Renhe Liu, Xiaoxuan Lyu, Mei-Hui Hsu, Catherine Vilcheze, Scott G Franzblau, William R Jacobs, Gurdyal S Besra, Eric F Johnson, Klaus Fütterer, Feng Wang
Mycobacterium tuberculosis (Mtb) DprE1, an essential isomerase for the biosynthesis of the mycobacterial cell wall, is a validated target for tuberculosis (TB) drug development. Here we report the X-ray crystal structures of DprE1 and the DprE1 resistant mutant (Y314C) in complexes with TCA1 derivatives to elucidate the molecular basis of their inhibitory activities and an unconventional resistance mechanism, which enabled us to optimize the potency of the analogs. The selected lead compound showed excellent in vitro and in vivo activities, and low risk of toxicity profile except for the inhibition of CYP2C9...
August 16, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28815428/the-pharmacology-and-toxicology-of-third-generation-anticonvulsant-drugs
#9
REVIEW
Paul LaPenna, Laura M Tormoehlen
Epilepsy is a neurologic disorder affecting approximately 50 million people worldwide, or about 0.7% of the population [1]. Thus, the use of anticonvulsant drugs in the treatment of epilepsy is common and widespread. There are three generations of anticonvulsant drugs, categorized by the year in which they were developed and released. The aim of this review is to discuss the pharmacokinetics, drug-drug interactions, and adverse events of the third generation of anticonvulsant drugs. Where available, overdose data will be included...
August 16, 2017: Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology
https://www.readbyqxmd.com/read/28815101/characterizing-the-strength-of-evidence-in-fda-labels-for-pharmacogenomic-biomarker-guided-medication-use
#10
Lauren Chin, Beth Devine, Sarah Baradaran, Katelyn Keyloun, William Canestaro, Jonathan Pham
There is great heterogeneity in drug treatment response that is thought to be due to individual-level allelic variation in pharmacogenomic biomarkers. FDA Drug Labels provide information to guide pharmacogenomic biomarker use. Yet, the strength of evidence for clinical validity and clinical utility is lacking. We characterized the strength of evidence and treatment recommendations contained in FDA Drug Labels as of December 2015. Pharmacogenomic biomarker information was provided for 137 drugs, involving 49 pharmacogenomic biomarkers, constituting 166 drug-biomarker pairs...
2017: AMIA Summits on Translational Science Proceedings
https://www.readbyqxmd.com/read/28814829/antibiotic-susceptibility-heteroresistance-and-updated-treatment-strategies-in-helicobacter-pylori-infection
#11
REVIEW
Maria Teresa Mascellino, Barbara Porowska, Massimiliano De Angelis, Alessandra Oliva
In this review, we discuss the problem of antibiotic resistance, heteroresistance, the utility of cultures and antibiotic susceptibility tests in Helicobacter pylori (Hp) eradication, as well as the updated treatment strategies for this infection. The prevalence of antibiotic resistance is increasing all over the world, especially for metronidazole and clarithromycin, because of their heavy use in some geographical areas. Heteroresistance (simultaneous presence of both susceptible and resistant strains in different sites of a single stomach) is another important issue, as an isolate could be mistakenly considered susceptible if a single biopsy is used for antimicrobial tests...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28814375/influencers-of-generic-drug-utilization-a-systematic-review
#12
REVIEW
Jennifer N Howard, Ilene Harris, Gavriella Frank, Zippora Kiptanui, Jingjing Qian, Richard Hansen
INTRODUCTION: With an increase in prescription drug spending and rising drug costs there is a need to encourage the use of generic prescription drugs. However, maximizing generic drug use is not possible without the public's positive perception and meeting their informational needs about generic drugs. Thus, improving the public's confidence in, and knowledge of generic drugs on the market is critical. The objective of this systematic review is to examine and evaluate the studies focusing on the nature and extent of key factors influencing generic drug use in the United States in order to help guide policy, education and practice interventions...
August 4, 2017: Research in Social & Administrative Pharmacy: RSAP
https://www.readbyqxmd.com/read/28814275/randomized-study-comparing-full-dose-monotherapy-s-1-followed-by-irinotecan-and-reduced-dose-combination-therapy-s-1-oxaliplatin-followed-by-s-1-irinotecan-as-initial-therapy-for-older-patients-with-metastatic-colorectal-cancer-nordic-9
#13
Stine Braendegaard Winther, Pia Österlund, Åke Berglund, Bengt Glimelius, Camilla Qvortrup, Halfdan Sorbye, Per Pfeiffer
BACKGROUND: Metastatic colorectal cancer (mCRC) is a disease of older age, but there is a relative lack of knowledge about effects of chemotherapy in older patients as they are under-represented in clinical trials. Little data can guide whether the strategy in older mCRC patients should be a sequential full-dose monotherapy chemotherapy approach or a dose-reduced combination chemotherapy approach. The oral 5FU prodrug S-1 seems to have less side effects than capecitabine and should be an optimal drug for older patients, but few data are available...
August 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28814111/ligand-efficiency-metrics-in-drug-discovery-the-pros-and-cons-from-a-practical-perspective
#14
Maria Maddalena Cavalluzzi, Giuseppe Felice Mangiatordi, Orazio Nicolotti, Giovanni Lentini
Ligand efficiency metrics are almost universally accepted as a valuable indicator of compound quality and an aid to reduce attrition. Areas covered: In this review, the authors describe ligand efficiency metrics giving a balanced overview on their merits and points of weakness in order to enable the readers to gain an informed opinion. Relevant theoretical breakthroughs and drug-like properties are also illustrated. Several recent exemplary case studies are discussed in order to illustrate the main fields of application of ligand efficiency metrics...
August 17, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28813639/exploitation-of-gene-expression-and-cancer-biomarkers-in-paving-the-path-to-era-of-personalized-medicine
#15
REVIEW
Hala Fawzy Mohamed Kamel, Hiba Saeed A Bagader Al-Amodi
Cancer therapy agents have been used extensively as cytotoxic drugs against tissue or organ of a specific type of cancer. With the better understanding of molecular mechanisms underlying carcinogenesis and cellular events during cancer progression and metastasis, it is now possible to use targeted therapy for these molecular events. Targeted therapy is able to identify cancer patients with dissimilar genetic defects at cellular level for the same cancer type and consequently requires individualized approach for treatment...
August 13, 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28813596/molecular-imaging-of-p-glycoprotein-in-chemoresistant-tumors-using-a-dual-modality-pet-fluorescence-probe
#16
Mengzhe Wang, Chengqiong Mao, Hui Wang, Xueying Ling, Zhanhong Wu, Zi-Bo Li, Xin Ming
Overexpression of P-glycoprotein (Pgp) has been considered a primary cause for multidrug resistance in a variety of cancers for three decades. However, clinical translation of Pgp targeted therapeutics has been hindered by lack of patient preselection based on the Pgp presence in tumors. We aim to develop a molecularly targeted probe for imaging tumoral Pgp in vivo with positron emission tomography (PET) and fluorescence, and to provide a tool for preselecting the patients with tumoral Pgp expression. Thus, a Pgp monoclonal antibody 15D3 was chemically modified with IRDye800 (IR800) and DOTA chelator...
August 16, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28812400/new-benzodiazepine-and-z-hypnotic-users-and-disability-pension-an-eight-year-nationwide-observational-follow-up-study
#17
Ingunn F Tvete, Trine Bjørner, Tor Skomedal
OBJECTIVE: To compare how newly initiated treatment with benzodiazepines, Z-hypnotics or both associates with the reception of disability pension among 40,661 individuals of a working age. DESIGN: Prescription register study. SETTING: Norwegian nationwide prescriptions socio-economic and disability status data. METHODS: Cox regression analyses. SUBJECTS: New benzodiazepine or Z-hypnotic users. MAIN OUTCOME MEASURE: Time to receive disability pension given benzodiazepine or Z-hypnotic use or both...
August 16, 2017: Scandinavian Journal of Primary Health Care
https://www.readbyqxmd.com/read/28811897/impact-of-in-vitro-chemosensitivity-test-guided-platinum-based-adjuvant-chemotherapy-on-the-surgical-outcomes-of-patients-with-p-stage-iiia-non-small-cell-lung-cancer-that-underwent-complete-resection
#18
Yuki Akazawa, Masahiko Higashiyama, Kazumi Nishino, Jyunji Uchida, Toru Kumagai, Takako Inoue, Ayako Fujiwara, Toshiteru Tokunaga, Jiro Okami, Fumio Imamura, Ken Kodama, Hisayuki Kobayashi
The impact of in vitro chemosensitivity test-guided platinum-based adjuvant chemotherapy on the surgical outcomes of patients undergoing complete resection for locally advanced non-small cell lung cancer (NSCLC) has yet to be elucidated. In the present study, the utility of adjuvant chemotherapy based on the collagen gel droplet embedded culture drug sensitivity test (CD-DST) in patients with p (pathology)-stage IIIA NSCLC was retrospectively analyzed. A series of 39 patients that had received platinum-based adjuvant chemotherapy following complete resection between 2007 and 2012 were enrolled...
September 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28811241/utility-of-prior-cultures-in-predicting-antibiotic-resistance-of-bloodstream-infections-due-to-gram-negative-pathogens-a-multicenter-observational-cohort-study
#19
Derek R MacFadden, Bryan Coburn, Nirav Shah, Ari Robicsek, Rachel Savage, Marion Elligsen, Nick Daneman
OBJECTIVES: Appropriate empiric antibiotic therapy in patients with bloodstream infections due to Gram-negative pathogens can improve outcomes. We evaluated the utility of prior microbiologic results for guiding empiric treatment in Gram-negative bloodstream infections. METHODS: We conducted a multi-center observational cohort study, in two large health systems in Canada and the United States, including 1,832 hospitalized patients with Gram-negative bloodstream infection (community, hospital, and ICU acquired) from April 2010 to March 2015...
August 12, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28811131/assessment-of-translational-risk-in-drug-research-role-of-biomarker-classification-and-mechanism-based-pkpd-concepts
#20
Sandra A G Visser, Tjerk J H Bueters
In 2005, Danhof and coauthors proposed a new biomarker classification in the context of the application of mechanism-based PKPD modeling. They defined the term 'biomarker' as a measure that characterizes a drug-induced response, which is on the causal path between drug administration and clinical outcome. The biomarker classification identified seven categories that provide different insights into the kinetics of drug action, such as target site distribution, target engagement, or into the impact of the drug on physiology or disease...
August 12, 2017: European Journal of Pharmaceutical Sciences
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