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https://www.readbyqxmd.com/read/28934455/drug-susceptibility-evaluation-of-an-influenza-a-h7n9-virus-by-analyzing-recombinant-neuraminidase-proteins
#1
Larisa V Gubareva, Katrina Sleeman, Zhu Guo, Hua Yang, Erin Hodges, Charles T Davis, Tatiana Baranovich, James Stevens
Background: Neuraminidase (NA) inhibitors are the recommended antiviral medications for influenza treatment. However, their therapeutic efficacy can be compromised by NA changes that emerge naturally and/or following antiviral treatment. Knowledge of which molecular changes confer drug resistance of influenza A(H7N9) viruses (group 2NA) remains sparse. Methods: Fourteen amino acid substitutions were introduced into the NA of A/Shanghai/2/2013(H7N9). Recombinant N9 (recN9) proteins were expressed in a baculovirus system in insect cells and tested using the Centers for Disease Control and Prevention standardized NA inhibition (NI) assay with oseltamivir, zanamivir, peramivir, and laninamivir...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28934348/antimicrobial-resistance-in-clinical-escherichia-coli-isolates-from-poultry-and-livestock-china
#2
Afrah Kamal Yassin, Jiansen Gong, Patrick Kelly, Guangwu Lu, Luca Guardabassi, Lanjing Wei, Xiangan Han, Haixiang Qiu, Stuart Price, Darong Cheng, Chengming Wang
Poultry and livestock are the most important reservoirs for pathogenic Escherichia coli and use of antimicrobials in animal farming is considered the most important factor promoting the emergence, selection and dissemination of antimicrobial-resistant microorganisms. The aim of our study was to investigate antimicrobial resistance in E. coli isolated from food animals in Jiangsu, China. The disc diffusion method was used to determine susceptibility to 18 antimicrobial agents in 862 clinical isolates collected from chickens, ducks, pigs, and cows between 2004 and 2012...
2017: PloS One
https://www.readbyqxmd.com/read/28934186/opioid-overdose-outbreak-west-virginia-august-2016
#3
Joel Massey, Michael Kilkenny, Samantha Batdorf, Sarah K Sanders, Debra Ellison, John Halpin, R Matthew Gladden, Danae Bixler, Loretta Haddy, Rahul Gupta
On August 15, 2016, the Mayor's Office of Drug Control Policy in Huntington, West Virginia, notified the Cabell-Huntington Health Department (CHHD) of multiple calls regarding opioid overdose received by the emergency medical system (EMS) during 3 p.m.-8 p.m. that day. A public health investigation and response conducted by the West Virginia Bureau for Public Health (BPH) and CHHD identified 20 opioid overdose cases within a 53-hour period in Cabell County; all cases included emergency department (ED) encounters...
September 22, 2017: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/28933798/pharmacokinetics-of-tecarfarin-and-warfarin-in-patients-with-severe-chronic-kidney-disease
#4
Mark Midei, Detlef Albrecht, Mintu P Turakhia, Daniel Ries, Thomas Marbury, William Smith, Debbie Dillon, Peter G Milner, Mark G Midei
Chronic kidney disease (CKD) complicates warfarin anticoagulation partially through its effect on CYP2C9 activity. Tecarfarin, a novel vitamin K antagonist, is not metabolized by CYP2C9. To evaluate the effect of CKD on their metabolism, we measured PK parameters of warfarin and tecarfarin in subjects with and without CKD. CKD subjects with estimated glomerular filtration rate < 30 mL/min not on dialysis (n = 13) were matched to healthy volunteers (HVs) (n = 10). Each subject was randomized to either warfarin 10 mg or tecarfarin 30 mg and was later crossed over to the other drug...
September 21, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28933367/targeting-metabolic-modulation-and-mitochondrial-dysfunction-in-the-treatment-of-heart-failure
#5
REVIEW
Abbey Steggall, Ify R Mordi, Chim C Lang
Despite significant improvements in morbidity and mortality with current evidence-based pharmaceutical-based treatment of heart failure (HF) over the previous decades, the burden of HF remains high. An alternative approach is currently being developed, which targets myocardial energy efficiency and the dysfunction of the cardiac mitochondria. Emerging evidence suggests that the insufficient availability of ATP to the failing myocardium can be attributed to abnormalities in the myocardial utilisation of its substrates rather than an overall lack of substrate availability...
May 10, 2017: Diseases (Basel)
https://www.readbyqxmd.com/read/28933312/characterization-of-imatinib-resistant-cml-leukemic-stem-initiating-cells-and-their-sensitivity-to-cbp-catenin-antagonists
#6
Yi Zhao, Kaijin Wu, Yongfeng Wu, Elizabeth Melendez, Goar Smbatyan, David Massiello, Michael Kahn
The development of the tyrosine kinase inhibitor Imatinib (IM) represents a milestone breakthrough in CML (Chronic Myeloid Leukemia) treatment. However, it is not curative and patients develop IM resistance. IM resistance has been previously correlated with the emergence of drug-resistant LIC/LSC (Leukemia Initiating Cell/Leukemia Stem Cell) and increased nuclear catenin levels and enhanced Wnt signaling. It has been demonstrated previously that drug resistant CML LIC/LSC can be safely eliminated both in vitro and in vivo via disruption of the CBP/catenin interaction, utilizing the highly biochemically selective small molecule CBP/catenin antagonist ICG-001...
September 19, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28933301/cysteine-rich-proteins-for-drug-delivery-and-diagnosis
#7
Guang Yang, Yue Lu, Hunter N Bomba, Zhen Gu
An emerging focus in nanomedicine is the exploration of multifunctional nanocomposite materials that integrate stimuli-responsive, therapeutic, and/or diagnostic functions. In this effort, cysteine-rich proteins have drawn considerable attention as a versatile platform due to their good biodegradability, biocompatibility, and ease of chemical modification. This review surveys cysteine-rich protein-based biomedical materials, including protein-metal nanohybrids, gold nanoparticle-protein agglomerates, protein-based nanoparticles, and hydrogels, with an emphasis on their preparation methods, especially those based on the cysteine residue-related reactions...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28933285/anticancer-and-reversing-multidrug-resistance-activities-of-natural-isoquinoline-alkaloids-and-their-structure-activity-relationship
#8
Zhi-Xing Qing, Jia-Lu Huang, Xue-Yi Yang, Jing-Hong Liu, Hua-Liang Cao, Feng Xiang, Pi Cheng, Jian-Guo Zeng
The severe anticancer situation as well as the emergence of multidrug-resistant (MDR) cancer cells has created an urgent need for the development of novel anticancer drugs with different mechanisms of action. A large number of natural alkaloids, such as paclitaxel, vinblastine and camptothecin have already been successfully developed into chemotherapy agents. Following the success of these natural products, in this review, twenty-six types of isoquinoline alkaloid (a total of 379 alkaloids), including benzyltetrahydroisoquinoline, aporphine, oxoaporphine, isooxoaporphine, dimeric aporphine, bisbenzylisoquinoline, tetrahydroprotoberberine, protoberberine, protopine, dihydrobenzophenanthridine, benzophenanthridine, benzophenanthridine dimer, ipecac, simple isoquinoline, pavine, montanine, erythrina, chelidonine, tropoloisoquinoline, azafluoranthene, phthalideisoquinoline, naphthylisoquinoline, lycorine, crinane, narciclasine, and phenanthridone, were summarized based on their cytotoxic and MDR reversing activities against various cancer cells...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28933281/influenza-virus-small-molecule-therapeutics-and-mechanisms-of-antiviral
#9
Julianna Han, Jasmine Perez, Adam Schafer, Han Cheng, Norton Peet, Lijun Rong, Balaji Manicassamy
Influenza viruses cause severe upper respiratory illness in young children and the elderly during seasonal epidemics. Influenza viruses also have the potential to cause pandemics with significant loss of life in all age groups. Although vaccination is one of the most effective methods to protect against seasonal epidemics, seasonal vaccines afford lowered protection against emerging variant strains and no protection against novel strains. Moreover, the efficacy of influenza virus vaccines is considerably lower in the elderly population...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28933075/-key-technologies-in-synthetic-biology-of-natural-products
#10
Xue-Jun Kuang, Li-Qiu Zou, Ying Li, Chao Sun, Shi-Lin Chen
Natural products with complex and diverse structures are the major sources of new drugs. The biosynthesis of natural products is considered to be one of the best ways to solve the problems of complex and scarce natural products. DNA assembly technology and genome editing technology are two key technologies in the emerging interdisciplinary field of synthetic biology. A number of novel DNA assembly methods developed in the last few years have paved the way for the engineering of high molecular weight DNA molecules, including whole genomes, hence, it can realize the reconstruction of the metabolic pathways and speed up optimization process...
November 2016: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28932979/tuberculous-meningitis-in-children-and-adults-new-insights-for-an-ancient-foe
#11
REVIEW
Alyssa Mezochow, Kiran Thakur, Christopher Vinnard
PURPOSE OF REVIEW: Tuberculous meningitis is the most devastating manifestation of infection with Mycobacterium tuberculosis and represents a medical emergency. Approximately one half of tuberculous meningitis patients die or suffer severe neurologic disability. The goal of this review will be to review the pathogenic, clinical, and radiologic features of tuberculous meningitis and to highlight recent advancements in translational and clinical science. RECENT FINDINGS: Pharmacologic therapy includes combination anti-tuberculosis drug regimens and adjunctive corticosteroids...
September 20, 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28932966/regorafenib-in-advanced-hepatocellular-carcinoma-hcc-considerations-for-treatment
#12
Kyung Kim, Reena Jha, Petra A Prins, Hongkun Wang, Monica Chacha, Marion L Hartley, Aiwu Ruth He
PURPOSE: We report our institutional observations of ten patients with advanced hepatocellular carcinoma (HCC) (seven and three were Child-Pugh class A and B, respectively) who received compassionate regorafenib therapy between June 2016 and January 2017. These patients did not fit the rigid criteria of a clinical trial and represented the use of regorafenib in an everyday clinic situation. METHODS: Regorafenib (160 mg P.O. daily) was administered to patients on a 4-week cycle (3 weeks on, 1 week off) until disease progression (assessed using mRECIST criteria) or discontinuation secondary to toxicity (assessed using CTCAE criteria)...
September 20, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28932928/a-phase-i-study-to-assess-the-mass-balance-excretion-and-pharmacokinetics-of-14-c-ixazomib-an-oral-proteasome-inhibitor-in-patients-with-advanced-solid-tumors
#13
Neeraj Gupta, Steven Zhang, Sandeepraj Pusalkar, Mihaela Plesescu, Swapan Chowdhury, Michael J Hanley, Bingxia Wang, Cindy Xia, Xiaoquan Zhang, Karthik Venkatakrishnan, Dale R Shepard
This two-part, phase I study evaluated the mass balance, excretion, pharmacokinetics (PK), and safety of ixazomib in patients with advanced solid tumors. In Part A of the study, patients received a single 4.1 mg oral solution dose of [(14)C]-ixazomib containing ~500 nCi total radioactivity (TRA), followed by non-radiolabeled ixazomib (4 mg capsule) on days 14 and 21 of the 35-day PK cycle. Patients were confined to the clinic for the first 168 h post dose and returned for 24 h overnight clinic visits on days 14, 21, 28, and 35...
September 21, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28932163/preparedness-of-dammam-primary-health-care-centers-to-deal-with-emergency-cases
#14
Sanaa S M Alsaad, Salma H S Abu-Grain, Dalia Y M El-Kheir
OBJECTIVES: The objective of the study was to assess the availability of human and nonhuman resources for emergency medical services (EMSs) at the primary health care (PHC) level. MATERIALS AND METHODS: A cross-sectional study with mixed research methods (quantitative and qualitative) was carried out in governmental PHC centers in Dammam, Eastern Province of Saudi Arabia, between September 2014 and January 2015. Using systematic random sampling technique, 13 out of 26 PHC centers were included in the study...
September 2017: Journal of Family & Community Medicine
https://www.readbyqxmd.com/read/28931490/gpcrs-emerging-anti-cancer-drug-targets
#15
REVIEW
Ainhoa Nieto Gutierrez, Patricia H McDonald
G protein-coupled receptors (GPCRs) constitute the largest and most diverse protein family in the human genome with over 800 members identified to date. They play critical roles in numerous cellular and physiological processes, including cell proliferation, differentiation, neurotransmission, development and apoptosis. Consequently, aberrant receptor activity has been demonstrated in numerous disorders/diseases, and as a result GPCRs have become the most successful drug target class in pharmaceuticals treating a wide variety of indications such as pain, inflammation, neurobiological and metabolic disorders...
September 17, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28931315/the-liver-toxicity-knowledge-base-lktb-and-drug-induced-liver-injury-dili-classification-for-assessment-of-human-liver-injury
#16
Shraddha Thakkar, Weida Tong, Minjun Chen, Hong Fang, Zhichao Liu, Ruth Roberts
Drug-induced liver injury (DILI) is challenging drug development, clinical practice and regulation. The Liver Toxicity Knowledge Base (LTKB) provides essential data for DILI study. Areas Covered: The LTKB provided various types of data that can be used to assess and predict DILI. Among much information available, several reference drug lists with annotated human DILI risk are of important. The LTKB DILI classification data include DILI severity concern determined by the FDA drug labeling, DILI severity score from the NIH LiverTox database, and other DILI classification schemes from the literature...
September 21, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28931235/monoclonal-antibody-protects-against-acinetobacter-baumannii-infection-by-enhancing-bacterial-clearance-and-evading-sepsis
#17
Travis B Nielsen, Paul Pantapalangkoor, Brian M Luna, Kevin W Bruhn, Jun Yan, Ken Dekitani, Sarah Hsieh, Brandon Yeshoua, Bryan Pascual, Evgeny Vinogradov, Kristine M Hujer, T Nicholas Domitrovic, Robert A Bonomo, Thomas A Russo, Magda Lesczcyniecka, Thomas Schneider, Brad Spellberg
Background: Extremely drug-resistant (XDR) Acinetobacter baumannii is one of the most commonly encountered, highly resistant pathogens requiring novel therapeutic interventions. Methods: We developed C8, a monoclonal antibody (mAb), by immunizing mice with sublethal inocula of a hypervirulent XDR clinical isolate. Results: C8 targets capsular carbohydrate on the bacterial surface, enhancing opsonophagocytosis. Treating with a single dose of C8 as low as 0...
August 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28930979/analysis-of-18fdg-pet-ct-imaging-as-a-tool-for-studying-mycobacterium-tuberculosis-infection-and-treatment-in-non-human-primates
#18
Alexander G White, Pauline Maiello, M Teresa Coleman, Jaime A Tomko, L James Frye, Charles A Scanga, Philana Ling Lin, JoAnne L Flynn
Mycobacterium tuberculosis remains the number one infectious agent in the world today. With the emergence of antibiotic resistant strains, new clinically relevant methods are needed that evaluate the disease process and screen for potential antibiotic and vaccine treatments. Positron Emission Tomography/Computed Tomography (PET/CT) has been established as a valuable tool for studying a number of afflictions such as cancer, Alzheimer's disease, and inflammation/infection. Outlined here are a number of strategies that have been employed to evaluate PET/CT images in cynomolgus macaques that are infected intrabronchially with low doses of M...
September 5, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28930958/perioperative-use-of-nonsteroidal-anti-inflammatory-drugs-and-the-risk-of-anastomotic-failure-in-emergency-general-surgery
#19
Nadeem N Haddad, Brandon R Bruns, Toby M Enniss, David Turay, Joseph V Sakran, Alisan Fathalizadeh, Kristen Arnold, Jason S Murry, Matthew M Carrick, Matthew C Hernandez, Margaret H Lauerman, Asad J Choudhry, David S Morris, Jose J Diaz, Herb A Phelan, Martin D Zielinski
BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used analgesic and anti-inflammatory adjuncts. Nonsteroidal anti-inflammatory drug administration may potentially increase the risk of postoperative gastrointestinal anastomotic failure (AF). We aim to determine if perioperative NSAID utilization influences gastrointestinal AF in emergency general surgery (EGS) patients undergoing gastrointestinal resection and anastomosis. METHODS: Post hoc analysis of a multi-institutional prospectively collected database was performed...
October 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28930822/five-years-experience-on-3-4-diaminopyridine-phosphate-in-lambert-eaton-syndrome-case-reports
#20
Simona Portaro, Teresa Brizzi, Stefano Sinicropi, Alberto Cacciola, Maria Cristina De Cola, Alessia Bramanti, Demetrio Milardi, Antonino Lupica, Placido Bramanti, Antonio Toscano, Carmelo Rodolico
RATIONALE: To report our experience on 7 patients (4 males and 3 females), affected by nonparaneoplastic Lambert-Eaton myasthenic syndrome, treated with 3,4-diaminopyridine phosphate (3,4-DAPP) either alone or in combination with other immunosuppressants or steroids. PATIENT CONCERNS: Patients have been evaluated at specific timepoints (ie, baseline and last 5 year follow-up), with neurological examination, autoantibodies against presynaptic voltage-gated Cav2.1 (P/Q type) calcium ion channel (VGCC) dosage, neurophysiological evaluation focusing on the increased amplitude of the compound muscle action potential (cMAP) after maximum voluntary effort, quantitative myasthenia gravis (QMG) and activities of daily living scales, and autonomic nervous system involvement evaluation...
September 2017: Medicine (Baltimore)
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