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https://www.readbyqxmd.com/read/28805566/botulinum-toxin-therapy-for-nonmotor-aspects-of-parkinson-s-disease
#1
Jarosław Sławek, Mariusz Madaliński
The medical treatment of Parkinson's disease (PD) is symptomatic both in terms of motor and nonmotor aspects. The nonmotor symptoms therapy should be taken into account as many of them negatively influence the quality of life and are treatable. Botulinum neurotoxin (BoNT) offers effective treatment for drooling and bladder dysfunctions and alternative treatment for constipation and pain related to parkinsonism. BoNT for drooling is probably the best-documented therapy for nonmotor symptoms by clinical trials...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28803761/an-in-silico-perspective-on-the-toxicodynamic-of-tetrodotoxin-and-analogues-a-tool-for-supporting-the-hazard-identification
#2
Luca Dellafiora, Gianni Galaverna, Chiara Dall'Asta
Tetrodotoxin (TTX) is a potent neurotoxin naturally found in terrestrial and marine animals targeting the voltage-gated sodium channels. Historically, TTX has raised food safety concerns mainly in the Asian countries due to the consumption of the typical pufferfish-derived delicacy fugu. However, the diffusion of TTX is getting wider today, reasonably threating in a close future a broader number of consumers than before. The understanding of TTX group toxicity is still incomplete as most of the analogues and metabolites found together with TTX are largely understudied...
August 10, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28803760/mechanism-of-action-of-botulinum-neurotoxin-unexpected-consequences
#3
REVIEW
Mark Hallett
Botulinum neurotoxin (BoNT) is a widely used therapeutic in part because its mechanism of action is much wider than initially expected. Since BoNT is taken up more avidly in active presynaptic terminals, there is some selectivity for weakening muscles involved in frequent involuntary movements. BoNT blocks gamma motoneurons as well as alpha motoneurons, hence reducing afferent spindle activity which appears to have a favorable effect. Some BoNT is retrogradely transported in the motor axons, leading at least to reduction in recurrent inhibition mediated by the Renshaw cell...
August 10, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28803438/inhibitor-of-endocannabinoid-deactivation-protects-against-in-vitro-and-in-vivo-neurotoxic-effects-of-paraoxon
#4
Karen L G Farizatto, Sara A McEwan, Vinogran Naidoo, Spyros P Nikas, Vidyanand G Shukla, Michael F Almeida, Aaron Byrd, Heather Romine, David A Karanian, Alexandros Makriyannis, Ben A Bahr
The anticholinesterase paraoxon (Pxn) is related to military nerve agents that increase acetylcholine levels, trigger seizures, and cause excitotoxic damage in the brain. In rat hippocampal slice cultures, high-dose Pxn was applied resulting in a presynaptic vulnerability evidenced by a 64% reduction in synapsin IIb (syn IIb) levels, whereas the postsynaptic protein GluR1 was unchanged. Other signs of Pxn-induced cytotoxicity include the oxidative stress-related production of stable 4-hydroxynonenal (4-HNE)-protein adducts...
August 12, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28802760/involvement-of-obliquus-capitis-inferior-muscle-in-dystonic-head-tremor
#5
A Schramm, D Huber, C Möbius, A Münchau, Z Kohl, T Bäumer
INTRODUCTION: Head tremor is a common feature in cervical dystonia (CD) and often less responsive to botulinum neurotoxin (BoNT) treatment than dystonic posturing. Ultrasound allows accurate targeting of deeper neck muscles. METHODS: In 35 CD patients with dystonic head tremor the depth and thickness of the splenius capitis (SPL), semispinalis capitis and obliquus capitis inferior muscles (OCI) were assessed using ultrasound. Ultrasound guided EMG recordings were performed from the SPL and OCI...
August 1, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28802703/identification-and-characterization-of-clostridium-botulinum-group-iii-field-strains-by-matrix-assisted-laser-desorption-ionization-time-of-flight-mass-spectrometry-maldi-tof-ms
#6
Luca Bano, Ilenia Drigo, Elena Tonon, Simone Pascoletti, Cinzia Puiatti, Fabrizio Anniballi, Bruna Auricchio, Florigio Lista, Cesare Montecucco, Fabrizio Agnoletti
Animal botulism is primarily due to botulinum neurotoxin (BoNT) types C, D or their chimeric variants C/D or D/C, produced by Clostridium botulinum group III, which appears to include the genetically indistinguishable Clostridium haemolyticum and Clostridium novyi. In the present study, we used matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI TOF MS) to identify and characterize 81 BoNT-producing Clostridia isolated in 47 episodes of animal botulism. The instrument's default database, containing no entries for Clostridium botulinum, permitted reliable identification of 26 strains at the genus level...
August 9, 2017: Anaerobe
https://www.readbyqxmd.com/read/28802641/enhanced-effects-of-dna-vaccine-against-botulinum-neurotoxin-serotype-a-by-targeting-antigen-to-dendritic-cells
#7
Bo-Yang Chen, Guo Zhou, Qing-Li Li, Jian-Sheng Lu, Dan-Yang Shi, Xiao-Bin Pang, Xiao-Wei Zhou, Yun-Zhou Yu, Pei-Tang Huang
As dendritic cells (DCs) play a critical role in priming antigen-specific immune responses, the efficacy of DNA vaccines may be enhanced by targeting the encoded antigen proteins to DCs. In this study, we constructed a DC-targeted DNA vaccine encoding the Hc domain of botulinum neurotoxin serotype A (AHc) fused with scDEC, a single-chain Fv antibody (scFv) specific for the DC-restricted antigen-uptake receptor DEC205. Intramuscular injections of mice with the DC-targeted DNA vaccine (pVAX1-scDEC-AHc) stimulated more DCs to mature than the non-targeted DNA vaccine (pVAX1-SAHc) in the splenocytes...
August 9, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28800600/botulinum-neurotoxin-c-mutants-reveal-different-effects-of-syntaxin-or-snap-25-proteolysis-on-neuromuscular-transmission
#8
Giulia Zanetti, Stefan Sikorra, Andreas Rummel, Nadja Krez, Elisa Duregotti, Samuele Negro, Tina Henke, Ornella Rossetto, Thomas Binz, Marco Pirazzini
Botulinum neurotoxin serotype C (BoNT/C) is a neuroparalytic toxin associated with outbreaks of animal botulism, particularly in birds, and is the only BoNT known to cleave two different SNARE proteins, SNAP-25 and syntaxin. BoNT/C was shown to be a good substitute for BoNT/A1 in human dystonia therapy because of its long lasting effects and absence of neuromuscular damage. Two triple mutants of BoNT/C, namely BoNT/C S51T/R52N/N53P (BoNT/C α-51) and BoNT/C L200W/M221W/I226W (BoNT/C α-3W), were recently reported to selectively cleave syntaxin and have been used here to evaluate the individual contribution of SNAP-25 and syntaxin cleavage to the effect of BoNT/C in vivo...
August 11, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28800585/comparative-pathogenomics-of-clostridium-tetani
#9
Jonathan E Cohen, Rong Wang, Rong-Fong Shen, Wells W Wu, James E Keller
Clostridium tetani and Clostridium botulinum produce two of the most potent neurotoxins known, tetanus neurotoxin and botulinum neurotoxin, respectively. Extensive biochemical and genetic investigation has been devoted to identifying and characterizing various C. botulinum strains. Less effort has been focused on studying C. tetani likely because recently sequenced strains of C. tetani show much less genetic diversity than C. botulinum strains and because widespread vaccination efforts have reduced the public health threat from tetanus...
2017: PloS One
https://www.readbyqxmd.com/read/28800335/an-overview-of-human-immunodeficiency-virus-type-1-associated-common-neurological-complications-does-aging-pose-a-challenge
#10
Anantha Ram Nookala, Joy Mitra, Nitish S Chaudhari, Muralidhar L Hegde, Anil Kumar
With increasing survival of patients infected with human immunodeficiency virus type 1 (HIV-1), the manifestation of heterogeneous neurological complications is also increasing alarmingly in these patients. Currently, more than 30% of about 40 million HIV-1 infected people worldwide develop central nervous system (CNS)-associated dysfunction, including dementia, sensory, and motor neuropathy. Furthermore, the highly effective antiretroviral therapy has been shown to increase the prevalence of mild cognitive functions while reducing other HIV-1-associated neurological complications...
August 9, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28798916/risk-benefit-assessment-of-monomethylmercury-and-omega-3-fatty-acid-intake-for-ringed-seal-consumption-with-particular-emphasis-on-vulnerable-populations-in-the-western-canadian-arctic
#11
Lena Gmelch, Holger Hintelmann, Brendan Hickie, Hermine Kienberger, Gary Stern, Michael Rychlik
Many northern Inuit communities rely on traditional food as major source of nourishment. An essential part of the traditional Arctic diet is marine mammals such as ringed seals or beluga. Being top predators, these animals are often highly contaminated with various toxins. In contrast, some tissues of marine mammals are also characterized by high amounts of n3-PUFAs (omega-3 polyunsaturated fatty acids). Here, we try to balance the risks associated with the consumption of different tissue types of ringed seals in terms of the neurotoxin monomethylmercury (MMHg) with the benefits of consumption due to high n3-PUFA concentrations...
2017: Frontiers in Nutrition
https://www.readbyqxmd.com/read/28796463/defensin-neurotoxin-dyad-in-a-basally-branching-metazoan-sea-anemone
#12
Chan-Hee Kim, Ye Jin Lee, Hye-Jin Go, Hye Young Oh, Tae Kwan Lee, Ji Been Park, Nam Gyu Park
Recent studies suggest that vertebrate and invertebrate defensins have evolved from two independent ancestors, and that both defensins could share origins with animal toxins. Here, we purified novel sea anemone neurotoxin (BDS)-like antimicrobial peptides (AMPs)-Crassicorin-I and its putative homolog (Crassicorin-II)-from the pharynx extract of an anthozoan sea anemone (Urticina crassicornis). Based on structural analyses and cDNA cloning, mature Crassicorin-I represents a cationic AMP likely generated from a precursor and comprising 40 amino acid residues, including six cysteines forming three intramolecular disulphide bonds...
August 10, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28792585/centrally-mediated-late-motor-recovery-after-botulinum-toxin-injection-case-reports-and-a-review-of-current-evidence
#13
Manuel F Mas, Sheng Li, Gerard E Francisco
OBJECTIVE: Botulinum neurotoxin is commonly utilized in neurorehabilitation as a treatment for focal spasticity. Clinical experience has yielded observations of late motor recovery after intramuscular injection of botulinum neurotoxin, that are not readily explained by the classical mechanism of action of the neurotoxin in controlling spasticity. These findings have triggered speculation regarding a botulinum neurotoxin mediated effect at the central level after peripheral intervention...
August 9, 2017: Journal of Rehabilitation Medicine
https://www.readbyqxmd.com/read/28790020/prenatal-choline-supplementation-attenuates-mk-801-induced-deficits-in-memory-motor-function-and-hippocampal-plasticity-in-adult-male-rats
#14
Chelsea A Nickerson, Alexandra L Brown, Waylin Yu, Yoona Chun, Melissa J Glenn
Choline is essential to the development and function of the central nervous system and supplemental choline during development is neuroprotective against a variety of insults, including neurotoxins like dizocilpine (MK-801). MK-801 is an NMDA receptor antagonist that is frequently used in rodent models of psychological disorders, particularly schizophrenia. At low doses, it causes cognitive impairments, and at higher doses it induces motor deficits, anhedonia, and neuronal degeneration. The primary goals of the present study were to investigate whether prenatal choline supplementation protects against the cognitive impairments, motor deficits, and neuropathologies that are precipitated by MK-801 administration in adulthood...
August 5, 2017: Neuroscience
https://www.readbyqxmd.com/read/28789870/relevance-of-the-nucleus-of-the-solitary-tract-gelatinous-part-in-learned-preferences-induced-by-intragastric-nutrient-administration
#15
María A Zafra, Antonio D Agüera, Filomena Molina, Amadeo Puerto
Food preferences have been investigated in Wistar rats utilizing a learned concurrent flavor preference behavioral procedure. Previous studies have demonstrated that the perivagal administration of neurotoxin capsaicin disrupts the learning of preferences induced by intragastric administration of rewarding nutrients (pre-digested milk). The vagus nerve projects almost exclusively towards the nucleus of the solitary tract (NST), a brain medullary gateway for visceral signals. The objective of this study was to investigate the participation of the lateral portion of the dorsomedial region, the gelatinous subnucleus (SolG), in the learning of a concurrent preference task...
August 5, 2017: Appetite
https://www.readbyqxmd.com/read/28783115/a-novel-surface-plasmon-resonance-biosensor-for-the-rapid-detection-of-botulinum-neurotoxins
#16
Kruti Patel, Shmuel Halevi, Paul Melman, John Schwartz, Shuowei Cai, Bal Ram Singh
Botulinum neurotoxins (BoNTs) are Category A agents on the NIAID (National Institute of Allergy and Infectious Diseases) priority pathogen list owing to their extreme toxicity and the relative ease of production. These deadly toxins, in minute quantities (estimated human i.v. lethal dose LD50 of 1-2 ng/kg body weight), cause fatal flaccid paralysis by blocking neurotransmitter release. The current gold standard detection method, the mouse-bioassay, often takes days to confirm botulism. Furthermore, there are no effective antidotes known to reverse the symptoms of botulism, and as a result, patients with severe botulism often require meticulous care during the prolonged paralytic illness...
August 7, 2017: Biosensors
https://www.readbyqxmd.com/read/28782388/nanotechnology-based-drug-delivery-of-ropinirole-for-parkinson-s-disease
#17
Emilia Barcia, Liudmila Boeva, Luis García-García, Karla Slowing, Ana Fernández-Carballido, Yaquelyn Casanova, Sofía Negro
A new drug delivery system is developed for ropinirole (RP) for the treatment of Parkinson's disease (PD) consisting of biodegradable poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). The formulation selected was prepared with 8 mg RP and 50 mg PLGA 502. This formulation exhibited mean encapsulation efficiency of 74.8 ± 8.2%, mean particle size lower than 155 nm, the zeta potential of -14.25 ± 0.43 mV and zero-order in vitro release of RP (14.13 ± 0.17 μg/h/10 mg NPs) for 5 d...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28774501/synaptic-vesicle-2c-and-its-synaptic-related-function
#18
REVIEW
Yan-Wei Hu, Lei Xiao, Lei Zheng, Qian Wang
Synaptic vesicle 2 C (SV2C) is a novel isoform belonging to the synaptic vesicle 2 (SV2) protein superfamily; a family of proteins known to have roles in vesicle trafficking, exocytosis and neurotransmission. In humans, SV2C is expressed in evolutionarily older brain regions, and is a known receptor for botulinum neurotoxin/A (BoNT/A), controlling glucose-evoked granule recruitment and regulating dopamine release, thus serving as a potential target molecule in the treatment of psychosis. In addition, recent researches have shown that SV2C regulates hypertension and accelerates venous thromboembolism (VTE) and coagulation pathways and may play roles in several non-nervous system diseases...
July 31, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28772184/assessing-the-ecotoxicity-of-potentially-neurotoxic-substances-evaluation-of-a-behavioural-parameter-in-the-embryogenesis-of-danio-rerio
#19
Fabian G Weichert, Carolin Floeter, Adriana S Meza Artmann, Ulrike Kammann
The pollution of the aquatic environment is currently characterised by a large number of contaminants, especially by mixtures of micro-pollutants including neurotoxins. The ecotoxicological consequences of this burden are not yet assessable. Within the present study, a new test method was applied which evaluates behavioural changes in zebrafish (Danio rerio) embryos to quantify the neurotoxic effect of selected chemicals. Changes in the frequency of spontaneous tail movements - a parameter of locomotion - occurring during embryogenesis was assessed as parameter for neurotoxic effects...
July 27, 2017: Chemosphere
https://www.readbyqxmd.com/read/28770820/identification-and-characterization-of-a-novel-botulinum-neurotoxin
#20
Sicai Zhang, Geoffrey Masuyer, Jie Zhang, Yi Shen, Daniel Lundin, Linda Henriksson, Shin-Ichiro Miyashita, Markel Martínez-Carranza, Min Dong, Pål Stenmark
Botulinum neurotoxins are known to have seven serotypes (BoNT/A-G). Here we report a new BoNT serotype, tentatively named BoNT/X, which has the lowest sequence identity with other BoNTs and is not recognized by antisera against known BoNTs. Similar to BoNT/B/D/F/G, BoNT/X cleaves vesicle-associated membrane proteins (VAMP) 1, 2 and 3, but at a novel site (Arg66-Ala67 in VAMP2). Remarkably, BoNT/X is the only toxin that also cleaves non-canonical substrates VAMP4, VAMP5 and Ykt6. To validate its activity, a small amount of full-length BoNT/X was assembled by linking two non-toxic fragments using a transpeptidase (sortase)...
August 3, 2017: Nature Communications
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