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https://www.readbyqxmd.com/read/28925695/nanomolar-inhibitors-of-glycogen-phosphorylase-based-on-%C3%AE-d-glucosaminyl-heterocycles-a-combined-synthetic-enzyme-kinetic-and-protein-crystallography-study
#1
Eva Bokor, Efthimios Kyriakis, Theodora Ga Solovou, Csenge Koppány, Anastassia L Kantsadi, Katalin E Szabó, Andrea Szakács, Georgios A Stravodimos, Tibor Docsa, Vassiliki T Skamnaki, Spyros E Zographos, Pál Gergely, Demetres D Leonidas, László Somsák
Aryl substituted 1-(β-D-glucosaminyl)-1,2,3-triazoles as well as C-β-D-glucosaminyl 1,2,4-triazoles and imidazoles were synthesized and tested as inhibitors against muscle and liver isoforms of glycogen phosphorylase (GP). While the N-β-D-glucosaminyl 1,2,3-triazoles showed weak or no inhibition, the C-β-D-glucosaminyl derivatives had potent activity and the best inhibitor was the 2-(β-D-glucosaminyl)-4(5)-(2-naphthyl)-imidazole with a Ki value of 143 nM against human liver GPa. An X-ray crystallography study of the rabbit muscle GPb inhibitor complexes revealed structural features of the strong binding, and offered an explanation for the differences in inhibitory potency between glucosyl and glucosaminyl derivatives and also for the differences between imidazole and 1,2,4-triazole analogues...
September 19, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28916119/safety-and-efficacy-of-glycerol-phenylbutyrate-for-management-of-urea-cycle-disorders-in-patients-aged-2months-to-2years
#2
Susan A Berry, Nicola Longo, George A Diaz, Shawn E McCandless, Wendy E Smith, Cary O Harding, Roberto Zori, Can Ficicioglu, Uta Lichter-Konecki, Beth Robinson, Jerry Vockley
INTRODUCTION: Glycerol phenylbutyrate (GPB) is approved in the US for the management of patients 2months of age and older with urea cycle disorders (UCDs) that cannot be managed with protein restriction and/or amino acid supplementation alone. Limited data exist on the use of nitrogen conjugation agents in very young patients. METHODS: Seventeen patients (15 previously on other nitrogen scavengers) with all types of UCDs aged 2months to 2years were switched to, or started, GPB...
September 8, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28836366/lipoteichoic-acid-upregulates-plasminogen-activator-inhibitor-1-expression-in-parapneumonic-effusions
#3
Kai-Ling Lee, Wei-Lin Chen, Ray-Jade Chen, Kevin S Lai, Chi-Li Chung
BACKGROUND AND OBJECTIVE: Parapneumonic effusion (PPE) is commonly caused by Gram-positive bacteria (GPB) and often presents with pleural loculation, which is characterized by overproduction of plasminogen activator inhibitor (PAI)-1. Lipoteichoic acid (LTA), a surface adhesion molecule of GPB, binds to the pleural mesothelium and triggers inflammation. However, the effects of LTA on PAI-1 expression in PPE and underlying mechanisms remain unclear. METHODS: Thirty consecutive patients with PPE were enrolled, including uncomplicated culture negative (CN, n = 11), Gram-negative bacteria (GNB, n = 7) and GPB (n = 12) groups stratified by pleural fluid characteristics and bacteriology, and the effusion PAI-1 levels were measured...
August 23, 2017: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/28836328/the-mns-glycophorin-variant-gp-mur-affects-differential-erythroid-expression-of-rh-rhag-transcripts
#4
K Hsu, M-S Kuo, C-C Yao, H-C Cheng, H-J Lin, Y-S Chan, M Lin
BACKGROUND: The band 3 macrocomplex (also known as the ankyrin-associated complex) on the red cell membrane comprises two interacting subcomplexes: a band 3/glycophorin A subcomplex, and a Rh/RhAG subcomplex. Glycophorin B (GPB) is a component of the Rh/RhAG subcomplex that is also structurally associated with glycophorin A (GPA). Expression of glycophorin B-A-B hybrid GP.Mur enhances band 3 expression and is associated with lower levels of Rh-associated glycoprotein (RhAG) and Rh polypeptides...
August 24, 2017: Vox Sanguinis
https://www.readbyqxmd.com/read/28828970/antimicrobial-resistance-patterns-of-the-gram-positive-bacteria-isolated-from-children-with-bloodstream-infection-in-an-iranian-referral-hospital-a-6-year-study
#5
Setareh Mamishi, Babak Pourakbari, Shima Mahmoudi, Mina Moradzadeh, Masoumeh Mahzari, Mohammad TaghiHaghi Ashtiani, Parin Tanzifi
BACKGROUND: Bloodstream infections (BSI) are considered as a serious cause of morbidity and mortality in pediatricschildren. The aim of this study was to depict report the common Gram-positive bacteria (GPB) responsible for bloodstream infections in children and determine their antimicrobial resistance patterns in Children Medical Center Hospital (CMC), ) Hospital, Tehran, Iran. METHODS: This retrospective study was conducted within a six-year period (March 2011 to September 2016) for pediatric patients with BSI...
August 21, 2017: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/28768269/a-potential-role-for-the-nod1-variant-rs6958571-in-gram-positive-blood-stream-infection-in-elbw-infants
#6
Venkatesh Sampath, Neil Mulrooney, Aloka L Patel, Jonathan Cohen, Liyun Zhang, Jeffery Garland, Pascal M Lavoie, John Dagle, Pippa Simpson
BACKGROUND: The genetic basis of sepsis susceptibility in preterm infants remains understudied. Herein, we investigated the nucleotide binding-oligomerization domain (NOD)-like receptor (NLR) family of immune receptors as putative loci for preterm sepsis susceptibility. OBJECTIVE: To determine whether single nucleotide polymorphisms (SNPs) in NLR genes are associated with blood stream infections (BSI) in premature infants. METHODS: An international cohort of infants with gestational age (GA) <35 weeks were genotyped for SNPs in the ATG16L1, CARD8, NLRP3, NOD2, and NOD1 genes...
August 3, 2017: Neonatology
https://www.readbyqxmd.com/read/28766267/iodine-status-after-bariatric-surgery-a-prospective-10-year-report-from-the-swedish-obese-subjects-sos-study
#7
Sofia Manousou, Lena M S Carlsson, Robert Eggertsen, Lena Hulthén, Peter Jacobson, Kerstin Landin-Wilhelmsen, Penelope Trimpou, Per-Arne Svensson, Helena Filipsson Nyström
CONTEXT: Bariatric surgery can lead to nutrient deficiencies. Gastric by-pass (GBP) entails restriction and malabsorption, whereas, vertical banded gastroplasty (VBG) is only restrictive. OBJECTIVE: The objective of this study is to study whether GBP-patients develop iodine deficiency from malabsorption, and if GBP- and VBG-patients develop lower 24-h urinary iodine excretion (24-UIE) than obese non-operated controls (OB-controls) due to lower iodine intake. DESIGN: The Swedish Obese Subjects (SOS) study is a prospective, non-randomized study of 4047 obese patients included 1987-2001, who chose bariatric surgery or non-surgical treatment...
August 2, 2017: Obesity Surgery
https://www.readbyqxmd.com/read/28760933/genetic-evidence-for-erythrocyte-receptor-glycophorin-b-expression-levels-defining-a-dominant-plasmodium-falciparum-invasion-pathway-into-human-erythrocytes
#8
Selasi Dankwa, Mudit Chaand, Usheer Kanjee, Rays H Y Jiang, Luis V Nobre, Jonathan M Goldberg, Amy K Bei, Mischka A Moechtar, Christof Grüring, Ambroise D Ahouidi, Daouda Ndiaye, Tandakha N Dieye, Souleymane Mboup, Michael P Weekes, Manoj T Duraisingh
Plasmodium falciparum, the parasite that causes the deadliest form of malaria, has evolved multiple proteins known as invasion ligands that bind to specific erythrocyte receptors to facilitate invasion of human erythrocytes. The EBA-175/glycophorin A (GPA) and Rh5/basigin ligand-receptor interactions, referred to as invasion pathways, have been the subject of intense study. In this study, we focused on the lesser characterized sialic acid-containing receptors glycophorin B (GPB) and glycophorin C (GPC). Through bioinformatic analysis, we identified extensive variation in glycophorin B transcript (GYPB) levels in individuals from Benin, suggesting selection from malaria pressure...
July 31, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28743807/genome-wide-screen-for-genes-involved-in-caenorhabditis-elegans-developmentally-timed-sleep
#9
Huiyan Huang, Chen-Tseh Zhu, Lukas L Skuja, Dustin J Hayden, Anne C Hart
In Caenorhabditis elegans, Notch signaling regulates developmentally timed sleep during the transition from L4 larval stage to adulthood (L4/A) . To identify core sleep pathways and to find genes acting downstream of Notch signaling, we undertook the first genome-wide, classical genetic screen focused on C. elegans developmentally timed sleep. To increase screen efficiency, we first looked for mutations that suppressed inappropriate anachronistic sleep in adult hsp::osm-11 animals overexpressing the Notch coligand OSM-11 after heat shock...
September 7, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28689911/effect-of-grinding-and-polishing-on-roughness-and-strength-of-zirconia
#10
Waad Khayat, Najla Chebib, Matthew Finkelman, Samer Khayat, Ala Ali
STATEMENT OF PROBLEM: The clinical applications of high-translucency monolithic zirconia restorations have increased. Chairside and laboratory adjustments of these restorations are inevitable, which may lead to increased roughness and reduced strength. The influence of grinding and polishing on high-translucency zirconia has not been investigated. PURPOSE: The purpose of this in vitro study was to compare the roughness averages (Ra) of ground and polished zirconia and investigate whether roughness influenced strength after aging...
July 7, 2017: Journal of Prosthetic Dentistry
https://www.readbyqxmd.com/read/28648081/in-silico-and-in-vitro-screening-for-p-glycoprotein-interaction-with-tenofovir-darunavir-and-dapivirine-an-antiretroviral-drug-combination-for-topical-prevention-of-colorectal-hiv-transmission
#11
Magda Swedrowska, Shirin Jamshidi, Abhinav Kumar, Charles Kelly, Khondaker Miraz Rahman, Ben Forbes
The aim of the study was to use in silico and in vitro techniques to evaluate whether a triple formulation of antiretroviral drugs (tenofovir, darunavir, and dapivirine) interacted with P-glycoprotein (P-gp) or exhibited any other permeability-altering drug-drug interactions in the colorectal mucosa. Potential drug interactions with P-gp were screened initially using molecular docking, followed by molecular dynamics simulations to analyze the identified drug-transporter interaction more mechanistically. The transport of tenofovir, darunavir, and dapivirine was investigated in the Caco-2 cell models and colorectal tissue, and their apparent permeability coefficient (Papp), efflux ratio (ER), and the effect of transporter inhibitors were evaluated...
August 7, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28596651/bacteremia-during-early-post-allogeneic-hematopoietic-stem-cell-transplantation-period-a-single-center-experience
#12
Amro Mohamed Sedky El-Ghammaz
Bacteremia is a significant complication of allogeneic hematopoietic stem cell transplantation (HSCT). We aimed to study bacteremia occurring during early post-transplant period at Bone Marrow Transplantation Unit of Ain Shams University regarding its risk factors and impact on survival. Patients performing allogeneic HSCT were followed up for occurrence of bacteremia. Survival status was assessed at 180 days post-transplant. Bacteremia occurred in 53.3 % of patients. On univariate analysis, CD34 +ve cell dose (P = 0...
June 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28561378/epidemiology-of-bloodstream-infections-after-myeloablative-and-non-myeloablative-allogeneic-hematopoietic-stem-cell-transplantation-a-single-center-cohort-study
#13
Lars I Gjaerde, Claus Moser, Henrik Sengeløv
BACKGROUND: Patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) often develop bloodstream infections (BSI). We aimed to describe the etiologies and antibiotic resistance patterns of BSI after allo-HSCT, and, as knowledge about the impact of conditioning regimen is limited, we looked at the incidence, timing, risk factors, and mortality of BSI separately for myeloablative (MA)- and non-myeloablative (NMA)-conditioned patients. METHODS: All 460 patients (207 MA- and 253 NMA-conditioned) who underwent their first allo-HSCT at our center from 2008 to 2013 were included in a historical cohort...
May 31, 2017: Transplant Infectious Disease: An Official Journal of the Transplantation Society
https://www.readbyqxmd.com/read/28552335/effect-of-air-blowing-duration-on-the-bond-strength-of-current-one-step-adhesives-to-dentin
#14
Jiale Fu, Pipop Saikaew, Shimpei Kawano, Ricardo M Carvalho, Matthias Hannig, Hidehiko Sano, Denis Selimovic
OBJECTIVES: To evaluate the influence of different air-blowing durations on the micro-tensile bond strength (μTBS) of five current one-step adhesive systems to dentin. METHODS: One hundred and five caries-free human molars and five current one-step adhesive systems were used: ABU (All Bond Universal, Bisco, Inc.), CUB (CLEARFIL™ Universal Bond, Kuraray), GPB (G-Premio BOND, GC), OBA (OptiBond All-in-one, Kerr) and SBU (Scotchbond Universal, 3M ESPE). The adhesives were applied to 600 SiC paper-flat dentin surfaces according to each manufacturer's instructions and were air-dried with standard, oil-free air pressure of 0...
August 2017: Dental Materials: Official Publication of the Academy of Dental Materials
https://www.readbyqxmd.com/read/28526864/a-broad-spectrum-bactericidal-lipopeptide-with-anti-biofilm-properties
#15
Ohad Meir, Fadia Zaknoon, Uri Cogan, Amram Mor
Previous studies of the oligoacyllysyl (OAK) series acyl-lysyl-lysyl-aminoacyl-lysine-amide, suggested their utility towards generating robust linear lipopeptide-like alternatives to antibiotics, although to date, none exhibited potent broad-spectrum bactericidal activity. To follow up on this premise, we produced a new analog (C14KKc12K) and investigated its properties in various media. Mechanistic studies suggest that C14KKc12K uses a non-specific membrane-disruptive mode of action for rapidly reducing viability of Gram-negative bacteria (GNB) similarly to polymyxin B (PMB), a cyclic lipopeptide used as last resort antibiotic...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28510691/nf-%C3%AE%C2%BAb-upregulation-through-epigenetic-silencing-of-ldoc1-drives-tumor-biology-and-specific-immunophenotype-in-group-a-ependymoma
#16
Andrea M Griesinger, Davis A Witt, Sydney T Grob, Sabrina R Georgio Westover, Andrew M Donson, Bridget Sanford, Jean M Mulcahy Levy, Randall Wong, Daniel C Moreira, John A DeSisto, Ilango Balakrishnan, Lindsey M Hoffman, Michael H Handler, Kenneth L Jones, Rajeev Vibhakar, Sujatha Venkataraman, Nicholas K Foreman
Background: Inflammation has been identified as a hallmark of high-risk Group A (GpA) ependymoma (EPN). Chronic interleukin (IL)-6 secretion from GpA tumors drives an immune suppressive phenotype by polarizing infiltrating monocytes. This study determines the mechanism by which IL-6 is dysregulated in GpA EPN. Methods: Twenty pediatric GpA and 21 pediatric Group B (GpB) EPN had gene set enrichment analysis for MSigDB Hallmark gene sets performed. Protein and RNA from patients and cell lines were used to validate transcriptomic findings...
October 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28285886/one-year-record-of-bioaerosols-and-particles-concentration-in-indo-gangetic-plain-implications-of-biomass-burning-emissions-to-high-level-of-endotoxin-exposure
#17
Prashant Rajput, Manzar Hussain Anjum, Tarun Gupta
Previous studies worldwide have suggested the potential role of bioaerosols as ice-nuclei and cloud-condensation nuclei. Furthermore, their participation in regulating the global carbon cycle urges systematic studies from different environmental conditions throughout the globe. Towards this through one-year study, conducted from June 2015-May 2016, we report on atmospheric abundance and variability of viable bioaerosols, organic carbon (OC) and particles number and deduced mass concentrations from Indo-Gangetic Plain (IGP; at Kanpur)...
May 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28024381/enabling-prussian-blue-with-tunable-localized-surface-plasmon-resonances-simultaneously-enhanced-dual-mode-imaging-and-tumor-photothermal-therapy
#18
Xiaojun Cai, Wei Gao, Linlin Zhang, Ming Ma, Tianzhi Liu, Wenxian Du, Yuanyi Zheng, Hangrong Chen, Jianlin Shi
Prussian blue (PB) has been used as a photothermal conversion agent to generate heat to induce localized damage to tumor. However, its therapeutic efficiency is far from satisfactory. One of the major obstacles is that the maximum NIR absorption peak of PB within 690-720 nm cannot be optimized near the wavelength of the laser to enhance its therapeutic efficiency. Herein, we report that the integration of Gd(3+) into PB nanocrystals (GPB NCs) enables PB with tunable localized surface plasmon resonances (LSPRs) from 710 to 910 nm, achieving the maximum NIR peak near the wavelength of the laser...
December 27, 2016: ACS Nano
https://www.readbyqxmd.com/read/27979420/procalcitonin-levels-in-bloodstream-infections-caused-by-different-sources-and-species-of-bacteria
#19
Sheng Tao Yan, Li Chao Sun, Hong Bing Jia, Wen Gao, Jian Ping Yang, Guo Qiang Zhang
OBJECTIVE: The aim of this study was to evaluate procalcitonin (PCT) diagnostic accuracy in discriminating gram-negative (GN) from gram-positive (GP) bloodstream infections and determining the relationship between PCT levels, infection sites, and pathogen types. METHODS: Clinical and laboratory data were collected from patients with blood culture (BC)-positive sepsis between January 2014 and December 2015. PCT levels at different infection sites were compared, as was the presence of GN and GP bloodstream infection...
April 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/27785765/long-term-effects-of-good-handling-practices-during-the-pre-weaning-period-of-crossbred-dairy-heifer-calves
#20
Luciana Pontes Silva, Aline Cristina Sant'Anna, Lívia Carolina Magalhães Silva, Mateus José Rodrigues Paranhos da Costa
The aim of this study was to determine whether applying good practices of handling during the pre-weaning period have long-term effects on behavioral and physiological indicators, health status, and average daily gain (ADG) of crossbred Bos taurus × Bos indicus heifer calves. During the pre-weaning period, 98 crossbred of Holstein × Gir heifer calves were allotted into three treatments: (1) good practices of handling + brushing (GPB; n = 25), (2) good practices of handling (GP; n = 25), and (3) control (n = 48)...
January 2017: Tropical Animal Health and Production
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