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https://www.readbyqxmd.com/read/28919466/intrastriatally-injected-botulinum-neurotoxin-a-differently-effects-cholinergic-and-dopaminergic-fibers-in-c57bl-6-mice
#1
Alexander Hawlitschka, Carsten Holzmann, Sarah Witt, Juliane Spiewok, Anne-Marie Neumann, Oliver Schmitt, Andreas Wree, Veronica Antipova
Unilateral intrastriatal BoNT-A injection abolished apomorphine-induced rotational behavior in a rat model of hemiparkinsonism (hemi-PD) up to 6 months. It was hypothesized that the beneficial effect of botulinum neurotoxin-A (BoNT-A) grounded on the reduction of the Parkinson's diseases (PD) associated striatal hypercholinism. Intrastriatal injection of BoNT-A was not cytotoxic in rat brain, but neuronal fiber swellings in the BoNT-A infiltrated striata appeared and named BoNT-A-induced varicosities (BiVs)...
September 14, 2017: Brain Research
https://www.readbyqxmd.com/read/28918229/design-of-modified-botulinum-neurotoxin-a1-variants-with-a-shorter-persistence-of-paralysis-and-duration-of-action
#2
Daniel Scheps, Manuela López de la Paz, Marcel Jurk, Fred Hofmann, Jürgen Frevert
Botulinum neurotoxins (BoNTs) are classified by their antigenic properties into seven serotypes (A-G) and in addition by their corresponding subtypes. They are further characterized by divergent onset and duration of effect. Injections of low doses of botulinum neurotoxins cause localized muscle paralysis that is beneficial for the treatment of several medical disorders and aesthetic indications. Optimizing the therapeutic properties could offer new treatment opportunities. This report describes a rational design approach to modify the pharmacological properties by mutations in the C-terminus of BoNT/A1 light chain (LC)...
September 13, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28913830/ontogenesis-of-opercular-deformities-in-gilthead-sea-bream-sparus-aurata-a-histological-description
#3
N P Thuong, B Verstraeten, B D Kegel, J Christiaens, T D Wolf, P Sorgeloos, D Bonte, D Adriaens
The aim of this study was to characterize histological changes during opercular osteogenesis in farmed gilthead sea bream Sparus aurata larvae from 7 to 69 days post hatching (dph) and compare normal osteogenesis with that of deformed opercles. Mild opercular deformities were first detected in 19 dph larvae by folding of the opercle's distal edge into the gill chamber. Here, the variation in the phenotype and the irregular bone structure at the curled part of the opercles is described and compared with the histology of normal opercles...
September 15, 2017: Journal of Fish Biology
https://www.readbyqxmd.com/read/28911764/global-respiratory-syncytial-virus-associated-mortality-in-young-children-rsv-gold-a-retrospective-case-series
#4
Nienke M Scheltema, Angela Gentile, Florencia Lucion, D James Nokes, Patrick K Munywoki, Shabir A Madhi, Michelle J Groome, Cheryl Cohen, Jocelyn Moyes, Kentigern Thorburn, Somsak Thamthitiwat, Hitoshi Oshitani, Socorro P Lupisan, Aubree Gordon, José F Sánchez, Katherine L O'Brien, Bradford D Gessner, Agustinus Sutanto, Asuncion Mejias, Octavio Ramilo, Najwa Khuri-Bulos, Natasha Halasa, Fernanda de-Paris, Márcia Rosane Pires, Michael C Spaeder, Bosco A Paes, Eric A F Simões, Ting F Leung, Maria Tereza da Costa Oliveira, Carla Cecília de Freitas Lázaro Emediato, Quique Bassat, Warwick Butt, Hsin Chi, Uzma Bashir Aamir, Asad Ali, Marilla G Lucero, Rodrigo A Fasce, Olga Lopez, Barbara A Rath, Fernando P Polack, Jesse Papenburg, Srđan Roglić, Hisato Ito, Edward A Goka, Diederick E Grobbee, Harish Nair, Louis J Bont
BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related mortality using individual patient data. METHODS: In this retrospective case series, we developed an online questionnaire to obtain individual patient data for clinical and socioeconomic characteristics of children aged younger than 5 years who died with community-acquired RSV infection between Jan 1, 1995, and Oct 31, 2015, through leading research groups for child pneumonia identified through a comprehensive literature search and existing research networks...
October 2017: Lancet Global Health
https://www.readbyqxmd.com/read/28898517/characterization-of-the-functional-activity-of-botulinum-neurotoxin-subtype-b6
#5
Tomoko Kohda, Keiji Nakamura, Koji Hosomi, Yasushi Torii, Shunji Kozaki, Masafumi Mukamoto
Clostridium botulinum produces the highly potent neurotoxin, botulinum neurotoxin (BoNT), which is classified into seven serotypes, A-G, and the subtype classification is confirmed by the diversity of the amino acid sequence among the serotypes. The BoNT from the Osaka05 strain is associated with type B infant botulism and has been divided into BoNT/B subtype B6 (BoNT/B6) by phylogenetic analysis and the antigenicity of its C-terminal heavy chain (HC) domain. However, the molecular basis for its properties, including the potency, is poorly understood...
September 12, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28891721/the-regions-on-the-light-chain-of-botulinum-neurotoxin-type-a-recognized-by-t-cells-from-toxin-treated-cervical-dystonia-patients-the-complete-human-t-cell-recognition-map-of-the-toxin-molecule
#6
Minako Oshima, Philip Deitiker, Joseph Jankovic, M Zouhair Atassi
We have recently mapped the in vitro proliferative responses of T cells from botulinum neurotoxin type A (BoNT/A)-treated cervical dystonia (CD) patients with overlapping peptides encompassing BoNT/A heavy chain (residues 449-1296). In the present study, we determined the recognition profiles, by peripheral blood lymphocytes (PBL) from the same set of patients, of BoNT/A light (L) chain (residues 1-453) by using 32 synthetic overlapping peptides that encompassed the entire L chain. Profiles of the T-cell responses (expressed in stimulation index, SI; Z score based on transformed SI) to the peptides varied among the patients...
September 11, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28888929/longitudinal-studies-of-botulinum-toxin-in-cervical-dystonia-why-do-patients-discontinue-therapy
#7
H A Jinnah, Cynthia L Comella, Joel Perlmutter, Codrin Lungu, Mark Hallett
BACKGROUND: Numerous studies have established botulinum toxin (BoNT) to be safe and effective for the treatment of cervical dystonia (CD). Despite its well-documented efficacy, there has been growing awareness that a significant proportion of CD patients discontinue therapy. The reasons for discontinuation are only partly understood. METHODS: This summary describes longitudinal studies that provided information regarding the proportions of patients discontinuing BoNT therapy, and the reasons for discontinuing therapy...
September 6, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28888928/an-update-on-new-and-unique-uses-of-botulinum-toxin-in-movement-disorders
#8
Joseph Jankovic
The therapeutic applications of botulinum toxin (BoNT) have grown manifold since its initial approval in 1989 by the US Food and Drug Administration (FDA) for the treatment of strabismus, blepharospasm, and other facial spasms. Although it is the most potent biologic toxin known to man, long-term studies have established its safety in the treatment of a variety of neurologic and non-neurologic disorders. This review focuses on some novel and uncommon uses of BoNT in the treatment of movement disorders, such as oromandibular dystonia, including bruxism, anterocollis, camptocormia, tremor, tics, tardive and levodopa-induced dyskinesia, and restless legs syndrome...
September 6, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28885076/late-mucosal-ulcers-in-dose-escalated-adaptive-dose-painting-treatments-for-head-and-neck-cancer
#9
Luiza Ana Maria Olteanu, Fréderic Duprez, Wilfried De Neve, Dieter Berwouts, Tom Vercauteren, Wouter Bauters, Philippe Deron, Wouter Huvenne, Katrien Bonte, Ingeborg Goethals, Julie Schatteman, Werner De Gersem
BACKGROUND: To identify predictive factors for the development of late grade 4 mucosal ulcers in adaptive dose-escalated treatments for head-and-neck cancer. MATERIAL AND METHODS: Patient data of four dose-escalated three-phase adaptive dose-painting by numbers (DPBN) clinical trials were analyzed in this study. Correlations between the development of late grade 4 ulcers and factors related with the treatment, disease characteristics and the patient were investigated...
September 8, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28884242/a-comparative-crossover-study-on-the-treatment-of-hemifacial-spasm-and-blepharospasm-preseptal-and-pretarsal-botulinum-toxin-injection-techniques
#10
Praween Lolekha, Arthita Choolam, Kongkiat Kulkantrakorn
Hemifacial spasm (HFS) and benign essential blepharospasm (BEB) are chronic and disabling abnormal craniofacial movements that produce involuntary eyelid twitching and closure. The efficacy and safety of botulinum toxin type A (BoNT-A) injections have been accepted and widely used for the treatment of HFS and BEB. However, different injection sites may influence the effectiveness, doses, and side effects. The aim of this study is to compare the efficacy, patient satisfaction, and complications of low-dose BoNT-A injections between injection at the preseptal (PS) and the pretarsal (PT) portion of the orbicularis oculi muscle...
September 7, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28879524/uptake-of-clostridial-neurotoxins-into-cells-and-dissemination
#11
Chloé Connan, Michel R Popoff
Clostridial neurotoxins, botulinum neurotoxins (BoNT) and tetanus neurotoxin (TeNT), are potent toxins, which are responsible for severe neurological diseases in man and animals. BoNTs induce a flaccid paralysis (botulism) by inhibiting acetylcholine release at the neuromuscular junctions, whereas TeNT causes a spastic paralysis (tetanus) by blocking the neurotransmitter release (glycine, GABA) in inhibitory interneurons within the central nervous system. Clostridial neurotoxins recognize specific receptor(s) on the target neuronal cells and enter via a receptor-mediated endocytosis...
September 7, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28879049/rituximab-in-early-systemic-sclerosis
#12
Maaike Boonstra, Jessica Meijs, Annemarie L Dorjée, Nina Ajmone Marsan, Anne Schouffoer, Maarten K Ninaber, Koen D Quint, Femke Bonte-Mineur, Tom W J Huizinga, Hans U Scherer, Jeska K de Vries-Bouwstra
OBJECTIVES: (1) Hypothesis testing of the potency of rituximab (RTX) in preventing fibrotic complications and (2) assessing acceptability and feasibility of RTX in early systemic sclerosis (SSc). METHODS: A small, 24-month, randomised, double-blind, placebo-controlled, single-centre trial in patients with SSc diagnosed <2 years was conducted. Patients received RTX or placebo infusions at t=0, t=15 days and t=6 months. Patients were clinically evaluated every 3 months, with lung function tests and high-resolution CT every other visit...
2017: RMD Open
https://www.readbyqxmd.com/read/28871080/genetically-engineered-red-cells-expressing-single-domain-camelid-antibodies-confer-long-term-protection-against-botulinum-neurotoxin
#13
Nai-Jia Huang, Novalia Pishesha, Jean Mukherjee, Sicai Zhang, Rhogerry Deshycka, Valentino Sudaryo, Min Dong, Charles B Shoemaker, Harvey F Lodish
A short half-life in the circulation limits the application of therapeutics such as single-domain antibodies (VHHs). We utilize red blood cells to prolong the circulatory half-life of VHHs. Here we present VHHs against botulinum neurotoxin A (BoNT/A) on the surface of red blood cells by expressing chimeric proteins of VHHs with Glycophorin A or Kell. Mice whose red blood cells carry the chimeric proteins exhibit resistance to 10,000 times the lethal dose (LD50) of BoNT/A, and transfusion of these red blood cells into naive mice affords protection for up to 28 days...
September 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28870555/botulinum-toxin-alleviates-dysphagia-of-patients-with-inclusion-body-myositis
#14
Aleksi Schrey, Laura Airas, Manu Jokela, Jaakko Pulkkinen
OBJECTIVES: Oropharyngeal dysphagia is a disabling and undertreated symptom that often occurs in patients with sporadic inclusion body myositis (s-IBM). In this study, we examined the effect of botulinum neurotoxin A (BoNT-A) injections to the cricopharyngeus muscle (CPM) of patients with s-IBM and dysphagia. PATIENTS, MATERIALS AND METHODS: A single-center retrospective study involving 40 biopsy-proven s-IBM-patients treated in the District of Southwest Finland from 2000 to 2013...
September 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28869522/recombinant-botulinum-neurotoxin-hc-subunit-bont-hc-and-catalytically-inactive-clostridium-botulinum-holoproteins-cibont-hps-as-vaccine-candidates-for-the-prevention-of-botulism
#15
Robert P Webb, Theresa J Smith, Leonard A Smith, Patrick M Wright, Rebecca L Guernieri, Jennifer L Brown, Janet C Skerry
There are few available medical countermeasures against botulism and the discontinuation of the pentavalent botulinum toxoid vaccine by the Centers for Disease Control and Prevention in 2011 has resulted in the need for a safe and effective prophylactic alternative. Advances in genetic engineering have resulted in subsequent vaccine efforts being primarily focused on the production of highly purified recombinant protein antigens representing one or more domains of the botulinum neurotoxin. Recombinant subunit vaccines based on the carboxy one-third of the toxin (Hc) developed in our lab against serotypes A-F have been shown to be safe and effective...
September 3, 2017: Toxins
https://www.readbyqxmd.com/read/28869493/vaccines-against-botulism
#16
REVIEW
Grace Sundeen, Joseph T Barbieri
Botulinum neurotoxins (BoNT) cause the flaccid paralysis of botulism by inhibiting the release of acetylcholine from motor neurons. There are seven serotypes of BoNT (A-G), with limited therapies, and no FDA approved vaccine for botulism. An investigational formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was used to vaccinate people who are at high risk of contracting botulism. However, this formalin-inactivated penta-serotype-BoNT/A-E toxoid vaccine was losing potency and was discontinued. This article reviews the different vaccines being developed to replace the discontinued toxoid vaccine...
September 2, 2017: Toxins
https://www.readbyqxmd.com/read/28843941/botulinum-neurotoxin-and-its-potential-role-in-the-treatment-of-erectile-dysfunction
#17
REVIEW
Hussein Ghanem, Amr Abdel Raheem, Islam Fathy Soliman AbdelRahman, Mark Johnson, Tarek Abdel-Raheem
INTRODUCTION: Botulinum toxin type A (BoNT-A) has been used to treat several striated and smooth muscle disorders. During the past year, human and animal studies conducted in Egypt and Canada by two different groups of investigators have suggested a possible role for the intracavernosal injection of BoNT-A in the treatment of erectile dysfunction (ED). AIM: To discuss BoNT-A and its current medical uses, the rationale for its new potential use in the treatment of ED, and the available evidence and concerns...
August 23, 2017: Sexual Medicine Reviews
https://www.readbyqxmd.com/read/28841849/the-diagnostic-pathway-of-parkinson-s-disease-a-cross-sectional-survey-study-of-factors-influencing-patient-dissatisfaction
#18
Annette O A Plouvier, Tim C Olde Hartman, Olga A de Bont, Sjoerd Maandag, Bastiaan R Bloem, Chris van Weel, Antoine L M Lagro-Janssen
BACKGROUND: The diagnostic pathway of Parkinson's disease (PD) is often complicated. Experiences during this pathway can affect patients' satisfaction and their confidence and trust in healthcare providers. Although healthcare providers cannot influence the impact of the diagnosis, they can influence how patients experience the pathway. This study, therefore, aims to provide insight into PD patients' dissatisfaction with the diagnostic pathway and to describe the factors that influence it...
August 25, 2017: BMC Family Practice
https://www.readbyqxmd.com/read/28840718/detection-and-quantification-of-biologically-active-botulinum-neurotoxin-serotypes-a-and-b-using-a-f%C3%A3-rster-resonance-energy-transfer-based-quantum-dot-nanobiosensor
#19
Yun Wang, H Christopher Fry, Guy E Skinner, Kristin M Schill, Timothy V Duncan
Botulinum neurotoxin (BoNT) is the most potent toxin known. The ingestion of food contaminated with biologically active BoNT causes foodborne botulism, which can lead to respiratory paralysis, coma, and death after ingestion of as little as 70 μg for a 70 kg human. Because of its lethality and challenges associated with current detection methods, there is an urgent need for highly sensitive rapid screening techniques capable of detecting biologically active BoNT. Here, we describe a Förster resonance energy transfer-based nanobiosensor that uses quantum dots (QDs) and two specific quencher-labeled peptide probes to detect and differentiate two biologically active forms of BoNT, serotypes A and B, which were responsible for 80% of human foodborne botulism cases in the U...
September 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28838993/prognostic-discrimination-based-on-the-eutos-long-term-survival-score-within-the-international-registry-for-chronic-myeloid-leukemia-in-children-and-adolescents
#20
Frédéric Millot, Joëlle Guilhot, Meinolf Suttorp, Adalet Maral Güneş, Petr Sedlacek, Evelyn De Bont, Chi Kong Li, Krzysztof Kalwak, Birgitte Lausen, Srdjana Culic, Michael Dworzark, Emilia Kaiserova, Barbara De Moerloose, Farah Roula, Andrea Biondi, André Baruchel
The EUTOS Long Term Survival score was tested in 350 children with chronic myeloid leukemia in first chronic phase treated with imatinib and registered in the International Registry for Childhood Chronic Myeloid Leukemia. With a median follow up of 3 years (range 1 month to 6 years) progression and/or death (whichever came first) occurred in 23 patients. For the entire cohort of patients the 5 year progression free survival was 92% (95% CI: 87%-94%) and 5 year survival accounting for chronic myeloid leukemia death was 97% (95% CI: 94%-99%)...
August 24, 2017: Haematologica
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