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https://www.readbyqxmd.com/read/29543291/anti-hiv-activity-of-new-higher-order-g-quadruplex-aptamers-obtained-from-tetra-end-linked-oligonucleotides
#1
F Nici, G Oliviero, A P Falanga, S D'Errico, M Marzano, D Musumeci, D Montesarchio, S Noppen, C Pannecouque, G Piccialli, N Borbone
By combining the ability of short G-rich oligodeoxyribonucleotides (ODNs) containing the sequence 5'CGGA3' to form higher order G-quadruplex (G4) complexes with the tetra-end-linked (TEL) concept to produce aptamers targeting the HIV envelope glycoprotein 120 (gp120), three new TEL-ODNs (1-3) having the sequence 5'CGGAGG3' were synthesized with the aim of studying the effect of G4 dimerization on their anti-HIV activity. Furthermore, in order to investigate the effect of the groups at the 5' position, the 5' ends of 1-3 were left uncapped (1) or capped with either the lipophilic dimethoxytrityl (DMT) (2) or the hydrophilic glucosyl-4-phosphate (3) moieties...
March 15, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29471122/conformational-mimetics-of-the-%C3%AE-methyl-chalcone-tub091-binding-tubulin-design-synthesis-and-antiproliferative-activity
#2
Oskía Bueno, Gloria Tobajas, Ernesto Quesada, Juan Estévez-Gallego, Sam Noppen, María-José Camarasa, José-Fernando Díaz, Sandra Liekens, Eva-María Priego, María-Jesús Pérez-Pérez
Based on the conformation of the α-methyl chalcone TUB091 in its complex with tubulin, a series of conformational mimetics have been designed and synthesized where the methyl group of the chalcone has been fused to phenyl ring B resulting in 1,2,3,4-tetrahydronaphthalen-2-yl aryl ketones. Among the synthesized compounds, the 5-amino-6-methoxy derivative, with a similar substitution pattern to that of TUB091, showed antiproliferative activity around 20 nM against tumor and endothelial cells. Tubulin binding experiments confirmed its binding to tubulin at the colchicine site with a Kb of 2...
February 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29464070/2-amino-3-methylcarboxy-5-heptyl-thiophene-tj191-is-a-selective-anti-cancer-small-molecule-that-targets-low-t%C3%AE-riii-expressing-malignant-t-cell-leukemia-lymphoma-cells
#3
Ahmed El-Gazzar, Sam Noppen, Joice Thomas, Wim Dehaen, Jan Balzarini, Sandra Liekens
Current chemotherapy regimens often include non-specific cytostatic/cytotoxic drugs, which do not distinguish between normal and tumor cells, therefore causing considerable systemic toxicity. We previously reported the synthesis and anti-proliferative activity of a novel synthetic 2-aminothiophene-3-carboxylic acid ester derivative TJ191 that selectively targets certain cancer cells without affecting the proliferation of other cancer cells or normal fibroblasts or immune cells (over 600-fold selectivity). In a panel of ten human T-cell leukemia/lymphoma cell lines and peripheral blood mononuclear cells (PBMCs), we now found that transforming growth factor β type III receptor (TβRIII) expression correlates inversely with TJ191 sensitivity, but not with sensitivity against classical chemotherapeutic drugs, thus serving as a predictive marker for TJ191 sensitivity...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29380586/we-still-lack-an-effective-method-to-identify-the-best-supraglottic-airway-device
#4
Marc Kriege, Tim Piepho, Rüdiger R Noppens
No abstract text is available yet for this article.
January 29, 2018: Minerva Anestesiologica
https://www.readbyqxmd.com/read/29335208/new-findings-on-the-d-tgggag-sequence-surprising-anti-hiv-1-activity
#5
Valeria Romanucci, Armando Zarrelli, Sandra Liekens, Sam Noppen, Christophe Pannecouque, Giovanni Di Fabio
The biological relevance of tetramolecular G-quadruplexes especially as anti-HIV agents has been extensively reported in the literature over the last years. In the light of our recent results regarding the slow G-quadruplex folding kinetics of ODNs based on d(TGGGAG) sequence, here we report a systematic anti-HIV screening to investigate the impact of the G-quadruplex folding on their anti-HIV activity. In particular, varying the single stranded concentrations of ODNs, it has been tested a pool of ODN sample solutions with different G-quadruplex concentrations...
February 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29327496/modulation-of-bace1-activity-by-chemically-modified-aptamers
#6
Cécile Gasse, Marwa Zaarour, Sam Noppen, Mikhail Abramov, Philippe Marlière, Sandra Liekens, Bart De Strooper, Piet Herdewijn
A modified DNA aptamer that binds BACE1, a therapeutic target involved in Alzheimer's disease has been developed. This ssXNA not only tightly binds to BACE1 but also inhibits its protease activity in vitro in the same range as a previously described unmodified aptamer. We report the in vitro selection of functional oligonucleotides incorporating two nucleobase modifications: 5-chlorouracil and 7-deazaadenine. The nucleoside analogue 5-chloro-2'-deoxyuridine has already been explored as a replacement for thymidine in a chemically modified genome of a bacterium...
April 4, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29237730/an-allosteric-binding-site-of-the-%C3%AE-7-nicotinic-acetylcholine-receptor-revealed-in-a-humanized-acetylcholine-binding-protein
#7
Florian Delbart, Marijke Brams, Fabian Gruss, Sam Noppen, Steve Peigneur, Sandro Boland, Patrick Chaltin, Jose Brandao-Neto, Frank von Delft, Wouter G Touw, Robbie P Joosten, Sandra Liekens, Jan Tytgat, Chris Ulens
Nicotinic acetylcholine receptors (nAChRs) belong to the family of pentameric ligand-gated ion channels and mediate fast excitatory transmission in the central and peripheral nervous systems. Among the different existing receptor subtypes, the homomeric α7 nAChR has attracted considerable attention because of its possible implication in several neurological and psychiatric disorders, including cognitive decline associated with Alzheimer's disease or schizophrenia. Allosteric modulators of ligand-gated ion channels are of particular interest as therapeutic agents, as they modulate receptor activity without affecting normal fluctuations of synaptic neurotransmitter release...
February 16, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29080649/interferon-lambda-ifn-%C3%AE-efficiently-blocks-norovirus-transmission-in-a-mouse-model
#8
Joana Rocha-Pereira, Sophie Jacobs, Sam Noppen, Eric Verbeken, Thomas Michiels, Johan Neyts
Human noroviruses are highly efficient in person to person transmission thus associated with explosive outbreaks of acute gastroenteritis. Outbreak control is limited to disinfection and isolation measures. Strategies to control the spread of noroviruses should be developed and models to study norovirus transmission will greatly facilitate this. Here, a mouse-to-mouse transmission model, in which mice develop acute murine norovirus (MNV)-induced diarrhea, was used to explore the role of interferon lambda (IFN-λ) in the control of a norovirus infection...
January 2018: Antiviral Research
https://www.readbyqxmd.com/read/28859114/using-king-vision-video-laryngoscope-with-a-channeled-blade-prolongs-time-for-tracheal-intubation-in-different-training-levels-compared-to-non-channeled-blade
#9
RANDOMIZED CONTROLLED TRIAL
Marc Kriege, Christian Alflen, Ruediger R Noppens
PURPOSE: It is generally accepted that using a video laryngoscope is associated with an improved visualization of the glottis. However, correctly placing the endotracheal tube might be challenging. Channeled video laryngoscopic blades have an endotracheal tube already pre-loaded, allowing to advance the tube once the glottis is visualized. We hypothesized that use of a channel blade with pre-loaded endotracheal tube results in a faster intubation, compared to a curved Macintosh blade video laryngoscope...
2017: PloS One
https://www.readbyqxmd.com/read/28827261/evaluation-of-the-mcgrath-mac-and-macintosh-laryngoscope-for-tracheal-intubation-in-2000-patients-undergoing-general-anaesthesia-the-randomised-multicentre-emma-trial-study-protocol
#10
Marc Kriege, Christian Alflen, Irene Tzanova, Irene Schmidtmann, Tim Piepho, Ruediger R Noppens
INTRODUCTION: The direct laryngoscopy technique using a Macintosh blade is the first choice globally for most anaesthetists. In case of an unanticipated difficult airway, the complication rate increases with the number of intubation attempts. Recently, McGrath MAC (McGrath) video laryngoscopy has become a widely accepted method for securing an airway by tracheal intubation because it allows the visualisation of the glottis without a direct line of sight. Several studies and case reports have highlighted the benefit of the video laryngoscope in the visualisation of the glottis and found it to be superior in difficult intubation situations...
August 21, 2017: BMJ Open
https://www.readbyqxmd.com/read/28376745/orogastric-tube-insertion-using-the-new-gastric-tube-guide-first-experiences-from-a-manikin-study
#11
Christian Alflen, Marc Kriege, Irene Schmidtmann, Rüdiger R Noppens, Tim Piepho
BACKGROUND: Orogastric tube placement is a common procedure routinely used in clinical anesthesiology and intensive care medicine. Nevertheless high failure rates and severe complications have been reported. We conducted this study to evaluate if the usage of the new gastric tube guide would speed up the placement of orogastric tubes and ease the procedure. METHODS: Thirty one professionals were given a hands-on-training in orogastric tube placement in a simulation manikin without and with the gastric tube guide...
April 4, 2017: BMC Anesthesiology
https://www.readbyqxmd.com/read/28322746/truncation-of-cxcl12-by-cd26-reduces-its-cxc-chemokine-receptor-4-and-atypical-chemokine-receptor-3-dependent-activity-on-endothelial-cells-and-lymphocytes
#12
Rik Janssens, Anneleen Mortier, Daiane Boff, Pieter Ruytinx, Mieke Gouwy, Bo Vantilt, Olav Larsen, Viktorija Daugvilaite, Mette M Rosenkilde, Marc Parmentier, Sam Noppen, Sandra Liekens, Jo Van Damme, Sofie Struyf, Mauro M Teixeira, Flávio A Amaral, Paul Proost
The chemokine CXCL12 or stromal cell-derived factor 1/SDF-1 attracts hematopoietic progenitor cells and mature leukocytes through the G protein-coupled CXC chemokine receptor 4 (CXCR4). In addition, it interacts with atypical chemokine receptor 3 (ACKR3 or CXCR7) and glycosaminoglycans. CXCL12 activity is regulated through posttranslational cleavage by CD26/dipeptidyl peptidase 4 that removes two NH2-terminal amino acids. CD26-truncated CXCL12 does not induce calcium signaling or chemotaxis of mononuclear cells...
May 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28264098/intravitreally-injected-fluid-dispersion-importance-of-injection-technique
#13
Koen Willekens, Geert Reyns, Marjan Diricx, Marc Vanhove, Bernard Noppen, Walter Coudyzer, Yicheng Ni, Jean H M Feyen, Peter Stalmans
Purpose: The purpose of this study was to evaluate the dispersion of intravitreally injected solutions and investigate the influence of varying injection techniques. Methods: This was a prospective study using enucleated porcine eyes and ultra-high-resolution computed tomography (UHRCT) scanning to visualize iomeprol intravitreal dispersion. Sixty eyes were divided over 12 different groups according to the injection procedure: fast (2 seconds) or slow (10 seconds) injection speed and needle tip location (6- and 12-mm needle shaft insertion or premacular tip placement verified by indirect ophthalmoscopy)...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28251605/the-novel-video-assisted-intubating-laryngeal-mask-totaltrack-compared-to-the-intubating-laryngeal-mask-fastrach-a-controlled-randomized-manikin-study
#14
RANDOMIZED CONTROLLED TRIAL
T Ott, A Barth, M Kriege, A Jahn-Eimermacher, T Piepho, R R Noppens
BACKGROUND: The novel Totaltrack combines a supraglottic airway device with video laryngoscopic tracheal intubation. The intubation laryngeal mask Fastrach is an established device without visual control of intubation. We hypothesized that supraglottic ventilation success with Totaltrack would be similar to Fastrach, but intubation would be performed faster due to visual control of the procedure. METHODS: Fifty-five anaesthesiologists were randomized into one of two study arms: Fastrach Totaltrack...
April 2017: Acta Anaesthesiologica Scandinavica
https://www.readbyqxmd.com/read/28194479/-airway-management-in-intensive-care-units-in-rhineland-palatinate-evolution-over-five-years
#15
T Piepho, T Härer, L Ellermann, R R Noppens
BACKGROUND: Securing the airway in severely ill patients is associated with a high rate of complications. So far, no information exists about the equipment readily available for airway management in German intensive care units (ICUs). It is also unknown if the range of material has improved over time. OBJECTIVES: In the present trial the availability of equipment for airway management in ICUs in Rhineland-Palatinate was evaluated at two different times. MATERIALS AND METHODS: Using a structured questionnaire, all ICUs in the state were contacted in the years 2010 and 2015...
May 2017: Der Anaesthesist
https://www.readbyqxmd.com/read/28152975/evaluation-of-the-optimal-cuff-volume-and-cuff-pressure-of-the-revised-laryngeal-tube-lts-d-in-surgical-patients
#16
Marc Kriege, Christian Alflen, Johannes Eisel, Thomas Ott, Tim Piepho, Ruediger R Noppens
BACKGROUND: Recent case reports have indicated significant cuff overinflation when using the standard filling volume based on the manufacturer's recommendations in older models of laryngeal tubes. The aim of this study was to determine the minimum cuff pressure needed to perform standardized ventilation without leakage in the new, revised model of the laryngeal tube "LTS-D". METHODS: After ethical approval, LTS-D was placed for ventilation in 60 anesthetized patients...
February 2, 2017: BMC Anesthesiology
https://www.readbyqxmd.com/read/28117793/topical-airway-anesthesia-for-awake-endoscopic-intubation-using-the-spray-as-you-go-technique-with-high-oxygen-flow
#17
Nina Pirlich, Jana A Lohse, Rüdiger R Noppens
A patient's willingness to cooperate is an absolute precondition for successful awake intubation of the trachea. Whilst drug-sedation of patients can jeopardize their spontaneous breathing, topical anesthesia of the airway is a popular technique. The spray-as-you-go technique represents one of the simplest opportunities to anesthetize the airway mucosa. The application of local anesthetic through the working channel of the flexible endoscope is a widespread practice for anesthetists as well as pulmonologists...
January 13, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28017762/structure-activity-relationship-studies-on-a-trp-dendrimer-with-dual-activities-against-hiv-and-enterovirus-a71-modifications-on-the-amino-acid
#18
Belén Martínez-Gualda, Liang Sun, Eva Rivero-Buceta, Aida Flores, Ernesto Quesada, Jan Balzarini, Sam Noppen, Sandra Liekens, Dominique Schols, Johan Neyts, Pieter Leyssen, Carmen Mirabelli, María-José Camarasa, Ana San-Félix
We have recently described a new class of dendrimers with tryptophan (Trp) on the surface that show dual antiviral activities against HIV and EV71 enterovirus. The prototype compound of this family is a pentaerythritol derivative with 12 Trps on the periphery. Here we complete the structure-activity relationship studies of this family to identify key features that might be significant for the antiviral activity. With this aim, novel dendrimers containing different amino acids (aromatic and non-aromatic), tryptamine (a "decarboxylated" analogue of Trp) and N-methyl Trp on the periphery have been prepared...
March 2017: Antiviral Research
https://www.readbyqxmd.com/read/27884026/-awake-video-laryngoscopy-an-alternative-to-awake-fiberoptic-intubation
#19
REVIEW
Jana Lohse, Rüdiger Noppens
INTRODUCTION: Awake video laryngoscopy is a novel option in airway management that is drawing more and more attention as an alternative to awake endoscopic guided intubation.Main issues: Intubation under preserved spontaneous breathing is the safest method to secure the expected difficult airway. In direct comparisons to awake flexible endoscopic intubation, awake video laryngoscopy achieves satisfactory intubation times and a high acceptance of patients and anesthesiologists. Specific cases, in particular very limited mouth opening or sub-glottic masses, require awake flexible endoscopic intubation...
November 2016: Anästhesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie: AINS
https://www.readbyqxmd.com/read/27853317/high-mannose-specific-lectin-msl-mediates-key-interactions-of-the-vaginal-lactobacillus-plantarum-isolate-cmpg5300
#20
Shweta Malik, Mariya I Petrova, Nicole C E Imholz, Tine L A Verhoeven, Sam Noppen, Els J M Van Damme, Sandra Liekens, Jan Balzarini, Dominique Schols, Jos Vanderleyden, Sarah Lebeer
To characterize the interaction potential of the human vaginal isolate Lactobacillus plantarum CMPG5300, its genome was mined for genes encoding lectin-like proteins. cmpg5300.05_29 was identified as the gene encoding a putative mannose-binding lectin. Phenotypic analysis of a gene knock-out mutant of cmpg5300.05_29 showed that expression of this gene is important for auto-aggregation, adhesion to the vaginal epithelial cells, biofilm formation and binding to mannosylated glycans. Purification of the predicted lectin domain of Cmpg5300...
November 17, 2016: Scientific Reports
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