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https://www.readbyqxmd.com/read/28220863/engineering-botulinum-neurotoxin-c1-as-a-molecular-vehicle-for-intra-neuronal-drug-delivery
#1
Edwin J Vazquez-Cintron, Phillip H Beske, Luis Tenezaca, Bao Q Tran, Jonathan M Oyler, Elliot J Glotfelty, Christopher A Angeles, Aurelia Syngkon, Jean Mukherjee, Suzanne R Kalb, Philip A Band, Patrick M McNutt, Charles B Shoemaker, Konstantin Ichtchenko
Botulinum neurotoxin (BoNT) binds to and internalizes its light chain into presynaptic compartments with exquisite specificity. While the native toxin is extremely lethal, bioengineering of BoNT has the potential to eliminate toxicity without disrupting neuron-specific targeting, thereby creating a molecular vehicle capable of delivering therapeutic cargo into the neuronal cytosol. Building upon previous work, we have developed an atoxic derivative (ad) of BoNT/C1 through rationally designed amino acid substitutions in the metalloprotease domain of wild type (wt) BoNT/C1...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209481/botulinum-toxin-type-a-reduces-inflammatory-hypernociception-induced-by-arthritis-in-the-temporomadibular-joint-of-rats
#2
Victor Ricardo Manuel Muñoz Lora, Juliana Trindade Clemente-Napimoga, Henrique Ballassini Abdalla, Cristina Gomes Macedo, Giancarlo de la Torre Canales, Celia Marisa Rizzatti Barbosa
OBJECTIVE: This study aimed to investigate the antinociceptive effects of Botulinum toxin type A (BoNT-A) on persistent inflammatory hypernociception induced by arthritis in the temporomandibular joint (TMJ) of rats. MATERIAL AND METHODS: Wistar rats were induced to persistent inflammatory hypernociception in the left TMJ. Then, animals were treated with intra-TMJ injections of BoNT-A, using doses of 3.5, 7 and 14 U/kg. Saline was used as control group. Behavioral tests were applied to evaluated the effect of BoNT-A in the inflammatory hypernociception...
February 14, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28207796/post-extubation-stridor-in-respiratory-syncytial-virus-bronchiolitis-is-there-a-role-for-prophylactic-dexamethasone
#3
Esther S Veldhoen, Charlotte A Smulders, Teus H Kappen, Job C Calis, Job van Woensel, Paulien A M Raymakers-Janssen, Louis J Bont, Marije P Hennus
AIM: The purpose of this study was to determine the incidence of reintubation due to upper airway obstruction in a homogeneous group of ventilated infants with Respiratory Syncytial Virus bronchiolitis. Our secondary objective was to determine whether prophylactic administration of dexamethasone prior to extubation was associated with decreased risk of reintubation. METHODS: This retrospective observational study in two Pediatric Intensive Care Units in 2 university hospitals in The Netherlands included two hundred patients younger than 13 months admitted with respiratory insufficiency caused by Respiratory Syncytial Virus bronchiolitis, requiring invasive mechanical ventilation...
2017: PloS One
https://www.readbyqxmd.com/read/28193825/correction-to-adaptation-to-fragmentation-evolutionary-dynamics-driven-by-human-influences
#4
Pierre-Olivier Cheptou, Anna L Hargreaves, Dries Bonte, Hans Jacquemyn
No abstract text is available yet for this article.
April 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28181679/mechanism-of-motor-coordination-of-masseter-and-temporalis-muscles-for-increased-masticatory-efficiency-in-mice
#5
Tomoko Yoshimi, Yoshiyuki Koga, Aya Nakamura, Ayumi Fujishita, Haruka Kohara, Emi Moriuchi, Keiko Yoshimi, Chi-Yang Tsai, Noriaki Yoshida
The demand for the use of mice as animal models for elucidating the pathophysiologies and pathogeneses of oral motor disorders has been increasing in recent years, as more and more kinds of genetically modified mice that express functional disorders of the stomatognathic system become available. However, the fundamental characteristics of mouse jaw movements during mastication have yet to be fully elucidated. The purpose of this study was to investigate the roles of the masseter and temporalis muscles, and the mechanisms of motor coordination of these muscles for increasing masticatory efficiency in the closing phase in mice...
February 9, 2017: Journal of Oral Rehabilitation
https://www.readbyqxmd.com/read/28169197/assessing-the-immediate-impact-of-botulinum-toxin-injection-on-impedance-of-spastic-muscle
#6
Xiaoyan Li, Henry Shin, Le Li, Elaine Magat, Sheng Li, Ping Zhou
This study aimed to investigate the immediate impacts of Botulinum Toxin A (BoNT-A) injections on the inherent electrical properties of spastic muscles using a newly developed electrical impedance myography (EIM) technique. Impedance measures were performed before and after a BoNT-A injection in biceps brachii muscles of 14 subjects with spasticity. Three major impedance variables, resistance (R), reactance (X) and phase angle (θ) were obtained from three different configurations, and were evaluated using the conventional EIM frequency at 50kHz as well as multiple frequency analysis...
February 3, 2017: Medical Engineering & Physics
https://www.readbyqxmd.com/read/28166806/the-we-study-does-botulinum-toxin-a-make-walking-easier-in-children-with-cerebral-palsy-study-protocol-for-a-randomized-controlled-trial
#7
Siri Merete Brændvik, Karin Roeleveld, Guro Lillemoen Andersen, Anne Elisabeth Ross Raftemo, Kjersti Ramstad, Jasmina Majkic-Tajsic, Torarin Lamvik, Bendik Lund, Turid Follestad, Torstein Vik
BACKGROUND: Intramuscular injections of botulinum toxin A (BoNT-A) have been a cornerstone in the treatment of spasticity for the last 20 years. In Norway, the treatment is now offered to two out of three children with spastic cerebral palsy (CP). However, despite its common use, the evidence for its functional effects is limited and inconclusive. The objective of this study is to determine whether BoNT-A makes walking easier in children with CP. We hypothesize that injections with BoNT-A in the calf muscles will reduce energy cost during walking, improve walking capacity, increase habitual physical activity, reduce pain and improve self-perceived performance and satisfaction...
February 6, 2017: Trials
https://www.readbyqxmd.com/read/28139761/genome-wide-association-study-of-polymorphisms-predisposing-to-bronchiolitis
#8
Anu Pasanen, Minna K Karjalainen, Louis Bont, Eija Piippo-Savolainen, Marja Ruotsalainen, Emma Goksör, Kuldeep Kumawat, Hennie Hodemaekers, Kirsi Nuolivirta, Tuomas Jartti, Göran Wennergren, Mikko Hallman, Mika Rämet, Matti Korppi
Bronchiolitis is a major cause of hospitalization among infants. Severe bronchiolitis is associated with later asthma, suggesting a common genetic predisposition. Genetic background of bronchiolitis is not well characterized. To identify polymorphisms associated with bronchiolitis, we conducted a genome-wide association study (GWAS) in which 5,300,000 single nucleotide polymorphisms (SNPs) were tested for association in a Finnish-Swedish population of 217 children hospitalized for bronchiolitis and 778 controls...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28137423/mechanism-of-inhibition-of-botulinum-neurotoxin-type-a-light-chain-by-two-quinolinol-compounds
#9
Yacoba V T Minnow, Ronald Goldberg, Sreedhar R Tummalapalli, David P Rotella, Nina M Goodey
Quinolinol-based compounds are a promising starting point for discovery of effective inhibitors of the clostridial neurotoxin, botulinum neurotoxin type A light chain (BoNT/A LC). Insights into the mechanism of inhibition by quinolinol compounds facilitate interpretation of docking data and inhibitor optimization. In this study, a fluorogenic substrate of BoNT/A, SNAPtide, was used to study the mechanism by which two new quinolinol compounds, MSU58 and MSU84, with IC50 values of 3.3 μM and 5.8 μM, respectively, inhibit BoNT/A LC...
January 28, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28119801/the-parc-lesion-a-proximal-avulsion-of-the-radiocarpal-capsule
#10
Francis Bonte, Christophe L Mathoulin
Purpose A proximal avulsion of the radiocarpal capsule (PARC) is a cause of persisting posttraumatic wrist pain. This lesion is often overlooked and left untreated during wrist arthroscopy. Materials and Methods A record review was performed on 13 patients with this lesion who underwent diagnostic wrist arthroscopy after failed conservative treatment. We retrospectively reviewed the results of an arthroscopic repair method in 13 patients. Results In 11 of the 13 consecutive cases the lesion was sutured using an arthroscopic dorsal capsule-ligamentous repair technique...
February 2017: Journal of Wrist Surgery
https://www.readbyqxmd.com/read/28113638/haptic-feedback-manipulation-during-botulinum-toxin-injection-therapy-for-focal-hand-dystonia-patients-a-possible-new-assistive-strategy
#11
Seyed Farokh Atashzar, Mahya Shahbazi, Christopher Ward, Olivia Samotus, Mehdi Delrobaei, Fariborz Rahimi, Jack Lee, Mallory Jackman, Mandar Jog, Rajni Patel
Abnormality of sensorimotor integration in the basal ganglia and cortex has been reported in the literature for patients with task-specific focal hand dystonia (FHD). In this study, we investigate the effect of manipulation of kinesthetic input in people living with writer's cramp disorder (a major form of FHD). For this purpose, severity of dystonia is studied for 11 participants while the symptoms of 7 participants have been tracked during 5 sessions of assessment and Botulinum toxin injection (BoNT-A) therapy (one of the current suggested therapies for dystonia)...
August 19, 2016: IEEE Transactions on Haptics
https://www.readbyqxmd.com/read/28110285/validation-of-a-clinical-screening-instrument-for-tumour-predisposition-syndromes-in-patients-with-childhood-cancer-tups-protocol-for-a-prospective-observational-multicentre-study
#12
Floor A M Postema, Saskia M J Hopman, Corianne A J M de Borgie, Peter Hammond, Raoul C Hennekam, Johannes H M Merks, Cora M Aalfs, Jakob K Anninga, Lieke Pv Berger, Fonnet E Bleeker, Eveline Sjm de Bont, Corianne Ajm de Borgie, Charlotte J Dommering, Natasha Ka van Eijkelenburg, Peter Hammond, Raoul C Hennekam, Marry M van den Heuvel-Eibrink, Saskia Mj Hopman, Marjolijn Cj Jongmans, Wijnanda A Kors, Tom Gw Letteboer, Jan Lcm Loeffen, Johannes Hm Merks, Maran Jw Olderode-Berends, Floor Am Postema, Anja Wagner
INTRODUCTION: Recognising a tumour predisposition syndrome (TPS) in patients with childhood cancer is of significant clinical relevance, as it affects treatment, prognosis and facilitates genetic counselling. Previous studies revealed that only half of the known TPSs are recognised during standard paediatric cancer care. In current medical practice it is impossible to refer every patient with childhood cancer to a clinical geneticist, due to limited capacity for routine genetic consultation...
January 20, 2017: BMJ Open
https://www.readbyqxmd.com/read/28106790/contributions-of-letter-speech-sound-learning-and-visual-print-tuning-to-reading-improvement-evidence-from-brain-potential-and-dyslexia-training-studies
#13
REVIEW
Gorka Fraga González, Gojko Žarić, Jurgen Tijms, Milene Bonte, Maurits W van der Molen
We use a neurocognitive perspective to discuss the contribution of learning letter-speech sound (L-SS) associations and visual specialization in the initial phases of reading in dyslexic children. We review findings from associative learning studies on related cognitive skills important for establishing and consolidating L-SS associations. Then we review brain potential studies, including our own, that yielded two markers associated with reading fluency. Here we show that the marker related to visual specialization (N170) predicts word and pseudoword reading fluency in children who received additional practice in the processing of morphological word structure...
January 18, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28099276/factors-in-the-efficacy-safety-and-impact-on-quality-of-life-for-treatment-of-drooling-with-botulinum-toxin-type-a-in-patients-with-cerebral-palsy
#14
Maria D Gonzalez-L, Carmen Martinez, Inma Bori Y Fortuny, Santiago Suso-Vergara
OBJECTIVE: To assess the efficacy and safety of botulinum toxin A (BoNT-A) injected in both submandibular and parotid versus only in parotid glands as a treatment for drooling in patients with spastic and dyskinetic cerebral palsy (CP), including an assessment of impact on quality of life (QoL) based on items from the International Classification of Functioning, Disability, and Health (ICF) core set. DESIGN: Forty patients with CP 18 years or older (mean, 21.8 years) participated in a prospective, single-center, randomized controlled interventional study...
February 2017: American Journal of Physical Medicine & Rehabilitation
https://www.readbyqxmd.com/read/28090659/the-effect-of-intradetrusor-botulinum-neurotoxin-type-a-on-urinary-ngf-tgf-beta-1-timp-2-levels-in-children-with-neurogenic-detrusor-overactivity-due-to-myelodysplasia
#15
Tuncay Top, Cagri Akin Sekerci, Banu Isbilen-Basok, Yiloren Tanidir, Ilker Tinay, Ferruh Kemal Isman, Cem Akbal, Ferruh Simsek, Tufan Tarcan
AIMS: The aim of this study was to determine the value of urine nerve growth factor (NGF), transforming growth factor beta 1 (TGF-Beta-1), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) levels to predict the urodynamic profile before and after botulinum neurotoxin type A (BoNT-A) treatment in children with myelodysplasia. METHODS: This prospective study included 15 children with myelodysplasia who underwent intradetrusor BoNT-A injections due to neurogenic detrusor overactivity (NDOA)...
January 16, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/28077492/dystonia-treatment-patterns-of-medication-use-in-an-international-cohort
#16
Sarah Pirio Richardson, Ashley R Wegele, Betty Skipper, Amanda Deligtisch, H A Jinnah
OBJECTIVE: To determine the frequency of medication use in patients with dystonia enrolled in an international biorepository study. METHODS: In a cross-sectional analysis, we included 2,026 participants enrolled at 37 sites in the United States, Canada, Europe, and Australia through Project 1 of the Dystonia Coalition, an international biorepository study. The primary aim was to assess the frequency of medication classes recommended for treating patients with dystonia, and the secondary aim was to compare characteristics (disease type, age, sex, duration of disease, comorbid conditions, severity)...
February 7, 2017: Neurology
https://www.readbyqxmd.com/read/28070870/defining-the-risk-and-associated-morbidity-and-mortality-of-severe-respiratory-syncytial-virus-infection-among-infants-with-congenital-heart-disease
#17
REVIEW
Paul A Checchia, Bosco Paes, Louis Bont, Paolo Manzoni, Eric A F Simões, Brigitte Fauroux, Josep Figueras-Aloy, Xavier Carbonell-Estrany
INTRODUCTION: The REGAL (RSV Evidence-a Geographical Archive of the Literature) series provide a comprehensive review of the published evidence in the field of respiratory syncytial virus (RSV) in Western countries over the last 20 years. This fourth publication covers the risk and burden of RSV infection in infants with congenital heart disease (CHD). METHODS: A systematic review was undertaken for articles published between January 1, 1995 and December 31, 2015 across PubMed, Embase, The Cochrane Library, and Clinicaltrials...
January 9, 2017: Infectious Diseases and Therapy
https://www.readbyqxmd.com/read/28050326/use-of-botulinum-neurotoxin-in-ophthalmology
#18
REVIEW
Emel Başar, Ceyhun Arıcı
Botulinum neurotoxin (BoNT) is the first biological toxin used in the treatment of ophthalmic diseases and to decrease skin wrinkles as an aesthetic agent. When used appropriately, it weakens the force of muscular contraction and/or inhibits glandular secretion. The most common areas for botulinum toxin treatment are the upper face, including the glabella, forehead, brows, and lateral canthal lines, or crow's feet. By relaxing the muscles causing wrinkles, non-permanent results may be achieved with its use...
December 2016: Turkish Journal of Ophthalmology
https://www.readbyqxmd.com/read/28043867/bont-ab-hybrid-maintains-similar-duration-of-paresis-as-bont-a-wild-type-in-murine-running-wheel-assay
#19
Anna Kutschenko, Marie-Christine Reinert, Nadja Krez, David Liebetanz, Andreas Rummel
The highly potent Botulinum neurotoxins (BoNT) are successful drugs to treat neuromuscular disorders. Efforts are being made to further reduce the injected BoNT dose and to lengthen the interval between treatments. Detailed knowledge of the BoNT structure-activity relationship (SAR) allows combining the best features of the different BoNT serotypes. Of all seven BoNT serotypes A-G, BoNT/A displays the highest potency despite low neuronal binding affinity, while BoNT/B exhibits much higher affinity. Recently, a new BoNT/AB hybrid (AABB) was constructed comprising the catalytic and translocation domain of BoNT/A and the 50kDa cell binding domain of BoNT/B...
December 30, 2016: Neurotoxicology
https://www.readbyqxmd.com/read/28043798/a-matrix-focused-structure-activity-and-binding-site-flexibility-study-of-quinolinol-inhibitors-of-botulinum-neurotoxin-serotype-a
#20
William A Harrell, Rebecca C Vieira, Susan M Ensel, Vicki Montgomery, Rebecca Guernieri, Vanessa S Eccard, Yvette Campbell, Virginia Roxas-Duncan, John H Cardellina, Robert P Webb, Leonard A Smith
Our initial discovery of 8-hydroxyquinoline inhibitors of BoNT/A and separation/testing of enantiomers of one of the more active leads indicated considerable flexibility in the binding site. We designed a limited study to investigate this flexibility and probe structure-activity relationships; utilizing the Betti reaction, a 36 compound matrix of quinolinol BoNT/A LC inhibitors was developed using three 8-hydroxyquinolines, three heteroaromatic amines, and four substituted benzaldehydes. This study has revealed some of the most effective quinolinol-based BoNT/A inhibitors to date, with 7 compounds displaying IC50 values ⩽1μM and 11 effective at ⩽2μM in an ex vivo assay...
November 9, 2016: Bioorganic & Medicinal Chemistry Letters
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