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https://www.readbyqxmd.com/read/28820574/thiol-containing-metallo-%C3%AE-lactamase-inhibitors-resensitize-resistant-gram-negative-bacteria-to-meropenem
#1
Kamaleddin Haj Mohammad Ebrahim Tehrani, Nathaniel I Martin
The prevalence of infections caused by metallo-β-lactamase (MBL) expressing Gram-negative bacteria has grown at an alarming rate in recent years. Despite the fact that MBLs can deactivate virtually all β-lactams antibiotics, there are as of yet no approved drugs available that inhibit their activity. We here examine the ability of previously reported thiol-based MBL inhibitors to synergize with meropenem against a panel of Gram-negative carbapenem-resistant isolates expressing different β-lactamases. Among the compounds tested, thiomandelic acid 3 and 2-merpto-3-phenylpropionic acid 4 were found to efficiently potentiate the activity of meropenem, especially against an IMP producing strain of K...
August 18, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28809565/dipicolinic-acid-derivatives-as-inhibitors-of-new-delhi-metallo-%C3%AE-lactamase-1
#2
Allie Y Chen, Pei W Thomas, Alesha C Stewart, Alexander Bergstrom, Zishuo Cheng, Callie Miller, Christopher R Bethel, Steven H Marshall, Cy V Credille, Christopher L Riley, Richard C Page, Robert A Bonomo, Michael W Crowder, David L Tierney, Walter Fast, Seth M Cohen
The efficacy of β-lactam antibiotics is threatened by the emergence and global spread of metallo-β-lactamase-(MBL) mediated resistance, specifically New Delhi-Metallo-β- lactamase-1 (NDM-1). Utilizing fragment-based drug discovery (FBDD), a new class of inhibitors for NDM-1 and two related β-lactamases, IMP-1 and VIM-2, was identified. Based on 2,6-dipicolinic acid (DPA), several libraries were synthesized for structure-activity relationship (SAR) analysis. Inhibitor 36 (IC50 = 80 nM) was identified to be highly selective for MBLs when compared to other Zn(II) metalloenzymes...
August 15, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28808062/ablating-tbc1d1-impairs-contraction-induced-sarcolemmal-glucose-transporter-type-4-redistribution-but-not-insulin-mediated-responses-in-rats
#3
Jamie Whitfield, Sabina Paglialunga, Brennan K Smith, Paula M Miotto, Genevieve Simnett, Holly L Robson, Swati S Jain, Eric A F Herbst, Eric M Desjardins, David J Dyck, Lawrence L Spriet, Gregory R Steinberg, Graham P Holloway
TBC1 domain family member 1 (TBC1D1), a Rab GTPase-activating protein and paralogue of Akt substrate of 160 kDa (AS160), has been implicated in both insulin- and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (AICAR)-mediated glucose transporter type (GLUT4) translocation. However, the role of TBC1D1 in contracting muscle remains ambiguous. We therefore explored the metabolic consequence of ablating TBC1D1 in both resting and contracting skeletal muscles, utilizing a rat TBC1D1-KO model...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28807096/a-five-year-surveillance-of-carbapenemase-producing-klebsiella-pneumoniae-in-a-pediatric-hospital-in-china-reveals-increased-predominance-of-ndm-1
#4
Fang Dong, Jie Lu, Yan Wang, Jin Shi, Jing Hui Zhen, Ping Chu, Yang Zhen, Shu Jing Han, Yong Li Guo, Wen Qi Song
OBJECTIVE: To characterize carbapenem (CPM)-non-susceptible Klebsiella pneumoniae (K. pneumoniae) and carbape-nemase produced by these strains isolated from Beijing Children's Hospital based on a five-year surveillance. METHODS: The Minimal Inhibition Concentration values for 15 antibiotics were assessed using the Phonix100 compact system. PCR amplification and DNA sequencing were used to detect genes encoding carbapenemases. WHONET 5.6 was finally used for resistance analysis...
August 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/28803054/decolorization-of-reactive-azo-dyes-using-a-sequential-chemical-and-activated-sludge-treatment
#5
Ken Meerbergen, Sam Crauwels, Kris A Willems, Raf Dewil, Jan Van Impe, Lise Appels, Bart Lievens
Textile wastewater contains high concentrations of organic substances derived from diverse dyes and auxiliary chemicals, some of which are non-biodegradable and/or toxic. Therefore, it is essential that textile wastewater is treated and that these substances are removed before being discharged into the environment. A combination of advanced oxidation processes (AOPs) to obtain partial dye degradation followed by a biological treatment has been suggested as a promising method for cost-effective decolorization of wastewater...
August 9, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28797449/nomogram-for-risk-prediction-of-malignant-transformation-in-oral-leukoplakia-patients-using-combined-biomarkers
#6
Xianglan Zhang, Ki-Yeol Kim, Zhenlong Zheng, Shadavlonjid Bazarsad, Jin Kim
OBJECTIVE: Squamous cell carcinomas (SCC) are the most common malignancies in the oral mucosa; these carcinomas have been preceded by potentially malignant oral disorders (PMODs), mostly oral leukoplakia (OL). No specific biomarker has been widely accepted for predicting the risk of malignant transformation of PMODs. The aim of this study was to develop an accurate prediction model for the malignant transformation of OL using clinical variables and candidate biomarkers. MATERIALS AND METHODS: To achieve this goal, 10 candidate biomarkers that had previously been reported as useful molecules were investigated: P53, Ki-67, P16, β-catenin, c-jun, c-met, insulin like growth factor II mRNA-binding protein (IMP-3), cyclooxygenase (COX-2), podoplanin (PDPN) and carbonic anhydrase 9 (CA9)...
September 2017: Oral Oncology
https://www.readbyqxmd.com/read/28780361/untreated-urban-waste-contaminates-indian-river-sediments-with-resistance-genes-to-last-resort-antibiotics
#7
Nachiket P Marathe, Chandan Pal, Swapnil S Gaikwad, Viktor Jonsson, Erik Kristiansson, D G Joakim Larsson
Efficient sewage treatment is critical for limiting environmental transmission of antibiotic-resistant bacteria. In many low and middle income countries, however, large proportions of sewage are still released untreated into receiving water bodies. In-depth knowledge of how such discharges of untreated urban waste influences the environmental resistome is largely lacking. Here, we highlight the impact of uncontrolled discharge of partially treated and/or untreated wastewater on the structure of bacterial communities and resistome of sediments collected from Mutha river flowing through Pune city in India...
July 25, 2017: Water Research
https://www.readbyqxmd.com/read/28776077/novel-formulation-of-abiraterone-acetate-might-allow-significant-dose-reduction-and-eliminates-substantial-positive-food-effect
#8
Tamás Solymosi, Zsolt Ötvös, Réka Angi, Betti Ordasi, Tamás Jordán, László Molnár, John McDermott, Vanessa Zann, Ann Church, Stuart Mair, Genovéva Filipcsei, Gábor Heltovics, Hristos Glavinas
PURPOSE: Zytiga (abiraterone acetate, AA) is known to exhibit very low bioavailability and a significant positive food effect in men. The unfavorable pharmacokinetic properties are attributed to the inadequate and variable dissolution of the compound. Using a continuous flow precipitation technology, a novel AA formulation has been developed with improved solubility and dissolution characteristics. The current study was performed to evaluate the pharmacokinetics and safety of this novel formulation in healthy volunteers...
August 3, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28764042/enzymatic-production-of-dietary-nucleotides-from-low-soluble-purine-bases-by-an-efficient-thermostable-and-alkali-tolerant-biocatalyst
#9
J Del Arco, J Cejudo-Sanches, I Esteban, V J Clemente-Suárez, D Hormigo, A Perona, J Fernández-Lucas
Traditionally, enzymatic synthesis of nucleoside-5'-monophosphates (5'-NMPs) using low water-soluble purine bases has been described as less efficient due to their low solubility in aqueous media. The use of enzymes from extremophiles, such as thermophiles or alkaliphiles, offers the potential to increase solubilisation of these bases by employing high temperatures or alkaline pH. This study describes the cloning, expression and purification of hypoxanthine-guanine-xanthine phosphoribosyltransferase from Thermus thermophilus (TtHGXPRT)...
December 15, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28762843/cost-effectiveness-of-3-month-paliperidone-therapy-for-chronic-schizophrenia-in-the-netherlands
#10
Thomas R Einarson, Basil G Bereza, Fadi Tedouri, Kristel Van Impe, Tom R Denee, Pieter J T Dries
BACKGROUND: A new depot formulation of paliperidone has been developed that provides effective treatment for schizophrenia for three months (PP3M). It has been tested in phase-3 trials, but no data on its cost-effectiveness have been published. PURPOSE: To determine the cost-effectiveness of PP3M compared with once-monthly paliperidone (PP1M), haloperidol long-acting therapy (HAL-LAT), risperidone microspheres (RIS-LAT), and oral olanzapine (oral-OLZ) for treating chronic schizophrenia in The Netherlands...
August 1, 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28760731/differential-nitric-oxide-derived-protein-modifications-of-flavin-containing-monooxygenases-in-type-1-allergic-mice
#11
Tadatoshi Tanino, Toru Bando, Akira Komada, Yukie Nojiri, Yuna Okada, Yukari Ueda, Eiichi Sakurai
Flavin-containing monooxygenases (FMOs) are major mammalian non-cytochrome P450 oxidative enzymes. T Helper2 cell-activated allergic diseases produce excess levels of nitric oxide (NO) that modify the functions of proteins. However, it remains unclear whether allergy-induced NO affects the pharmacokinetics of drugs metabolized by FMOs. This study investigated alterations of hepatic microsomal FMO1 and FMO3 activities in type 1 allergic mice, and further examined the interaction of FMO1 and FMO3 with allergy-induced NO...
July 31, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28758314/child-and-parental-executive-functioning-in-type-1-diabetes-their-unique-and-interactive-role-toward-treatment-adherence-and-glycemic-control
#12
Eveline R Goethals, Maartje de Wit, Nady Van Broeck, Jurgen Lemiere, Dagmar Van Liefferinge, Susanne Böhler, Marian De Wulf, Elke Dello, Jolien Laridaen, Lynn Van Hecke, Shana Van Impe, Kristina Casteels, Koen Luyckx
OBJECTIVE: Managing type 1 diabetes (T1D) requires the ability to make complex and critical decisions regarding treatment, to execute complex tasks accurately, and to make adjustments when problems arise. This requires effective neuropsychological competences of patients and their families, especially in the domain of executive functioning (EF): the ability to self-monitor, plan, solve problems, and set priorities. Previous research focused mainly on child EF, neglecting the impact of parental EF...
July 30, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28758223/metabonomics-profiling-of-marinated-meat-in-soy-sauce-during-processing
#13
Yang Yang, Yangfang Ye, Daodong Pan, Yangying Sun, Ying Wang, Jinxuan Cao
BACKGROUND: Marinated meat in soy sauce is one of the most popular traditional cured meat products in China. Its taste quality is directly related to primary and secondary metabolites. Herein, the change of metabolite composition of marinated meat in soy sauce during processing was systematically characterized using (1) H NMR and multivariate data analysis. RESULTS: The marinated meat in soy sauce metabonome was dominated by 26 metabolites, including amino acids, sugars, organic acids, nucleic aides and their derivatives...
July 31, 2017: Journal of the Science of Food and Agriculture
https://www.readbyqxmd.com/read/28755377/reconstitution-of-membrane-proteins-into-nanodiscs-for-single-particle-electron-microscopy
#14
Laetitia Daury, Jean-Christophe Taveau, Dimitri Salvador, Marie Glavier, Olivier Lambert
The structure determination of integral membrane protein (IMP) in lipid environment is particularly challenging. Among emerging methods for exchanging detergent required for IMP purification by original compounds, the use of lipid nanodisc preserves a lipid environment. Compared with the classical method of proteoliposome formation, the nanodisc technology provides a better control of IMP molecules inserted in lipid membrane, therefore giving access to structural methodologies developed for soluble proteins...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28752025/biased-activity-of-soluble-guanylyl-cyclase-the-janus-face-of-thymoquinone
#15
REVIEW
Charlotte Detremmerie, Paul M Vanhoutte, Susan Leung
The natural compound thymoquinone, extracted from Nigella sativa (black cumin), is widely used in humans for its anti-oxidative properties. Thymoquinone is known for its acute endothelium-independent vasodilator effects in isolated rat aortae and pulmonary arteries, depending in part on activation of adenosine triphosphate-sensitive potassium channels and inhibition of voltage-dependent calcium channels. The compound also improves endothelial dysfunction in mesenteric arteries of ageing rodents and in aortae of rabbits treated with pyrogallol, by inhibiting oxidative stress...
July 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28750094/crystal-structure-and-kinetic-analysis-of-the-class-b3-di-zinc-metallo-%C3%AE-lactamase-lra-12-from-an-alaskan-soil-metagenome
#16
María Margarita Rodríguez, Raphaël Herman, Barbara Ghiglione, Frédéric Kerff, Gabriela D'Amico González, Fabrice Bouillenne, Moreno Galleni, Jo Handelsman, Paulette Charlier, Gabriel Gutkind, Eric Sauvage, Pablo Power
We analyzed the kinetic properties of the metagenomic class B3 β-lactamase LRA-12, and determined its crystallographic structure in order to compare it with prevalent metallo-β-lactamases (MBLs) associated with clinical pathogens. We showed that LRA-12 confers extended-spectrum resistance on E. coli when expressed from recombinant clones, and the MIC values for carbapenems were similar to those observed in enterobacteria expressing plasmid-borne MBLs such as VIM, IMP or NDM. This was in agreement with the strong carbapenemase activity displayed by LRA-12, similar to GOB β-lactamases...
2017: PloS One
https://www.readbyqxmd.com/read/28744664/evaluation-of-the-carba-np-test-for-carbapenemase-detection-in-enterobacteriaceae-pseudomonas-spp-and-acinetobacter-spp-and-its-practical-use-in-the-routine-work-of-a-national-reference-laboratory-for-susceptibility-testing
#17
E Literacka, M Herda, A Baraniak, D Żabicka, W Hryniewicz, A Skoczyńska, M Gniadkowski
The aim of this study was to evaluate the Carba NP test (and CarbAcineto) for the detection of carbapenemases in Enterobacteriaceae, Pseudomonas spp. and Acinetobacter spp., and to assess its usefulness in the routine work of the National Reference Centre for Susceptibility Testing (NRCST) in Poland. The evaluation of the Carba NP/CarbAcineto tests was carried out on a group of 81 Enterobacteriaceae, Pseudomonas spp. and Acinetobacter spp. isolates producing KPC-, NDM-, VIM-, IMP- or OXA-48, -23, -24/40, -58-type carbapenemases, and on 26 carbapenemase-negative strains cultivated on a broad panel of microbiological media...
July 25, 2017: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/28743681/development-and-testing-of-an-intelligent-pain-management-system-ipms-on-mobile-phones-through-a-randomized-trial-among-chinese-cancer-patients-a-new-approach-in-cancer-pain-management
#18
Yunheng Sun, Feng Jiang, Juan J Gu, Y Ken Wang, Hongwei Hua, Jing Li, Zhijun Cheng, Zhijun Liao, Qian Huang, Weiwei Hu, Gang Ding
BACKGROUND: Cancer has become increasingly prevalent in China over the past few decades. Among the factors that determine the quality of life of cancer patients, pain has commonly been recognized as a most critical one; it could also lead to the ineffective treatment of the cancer. Driven by the need for better pain management for cancer patients, our research team developed a mobile-based Intelligent Pain Management System (IPMS). OBJECTIVE: Our objective was to design, develop, and test the IPMS to facilitate real-time pain recording and timely intervention among cancer patients with pain...
July 25, 2017: JMIR MHealth and UHealth
https://www.readbyqxmd.com/read/28741678/recent-advances-of-microbial-breeding-via-heavy-ion-mutagenesis-at-imp
#19
REVIEW
Wei Hu, Wenjian Li, Jihong Chen
Nowadays, the value of heavy ion mutagenesis has been accepted as a novel powerful mutagen technique to generate new microbial mutants due to its high linear energy transfer (LET) and high relative biological effectiveness (RBE). This paper briefly reviews recent progress in developing a more efficient mutagenesis technique for microbial breeding using heavy-ion mutagenesis, and also presents the outline of the beam line for microbial breeding in Heavy Ion Research Facility of Lanzhou (HIRFL). Then, new insights into microbial biotechnology via heavy-ion mutagenesis are also further explored...
July 25, 2017: Letters in Applied Microbiology
https://www.readbyqxmd.com/read/28741291/is-personality-associated-with-secondhand-harm-from-drinking
#20
Parnell Davis MacNevin, Kara Thompson, Michael Teehan, Heather Stuart, Sherry Stewart
BACKGROUND: Prior research suggests more than 70% of undergraduates have experienced harm from other students' drinking. This study built on the literature by, first, investigating whether secondhand harm cluster into latent factors that reflect distinct but related types of harm. Second, given the paucity of research examining factors that increase students' vulnerability to secondhand harm, we examined dimensions from Castellanos-Ryan and Conrod's 4-factor personality model for alcohol disorders (impulsivity [IMP], sensation seeking [SS], hopelessness [HOP], anxiety sensitivity [AS]) as predictors of secondhand harm exposure...
July 24, 2017: Alcoholism, Clinical and Experimental Research
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