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https://www.readbyqxmd.com/read/28333097/effects-of-a-sativex-like-combination-of-phytocannabinoids-on-disease-progression-in-r6-2-mice-an-experimental-model-of-huntington-s-disease
#1
Sara Valdeolivas, Onintza Sagredo, Mercedes Delgado, Miguel A Pozo, Javier Fernández-Ruiz
Several cannabinoids afforded neuroprotection in experimental models of Huntington's disease (HD). We investigated whether a 1:1 combination of botanical extracts enriched in either ∆⁸-tetrahydrocannabinol (∆⁸-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex(®), is beneficial in R6/2 mice (a transgenic model of HD), as it was previously shown to have positive effects in neurotoxin-based models of HD. We recorded the progression of neurological deficits and the extent of striatal deterioration, using behavioral, in vivo imaging, and biochemical methods in R6/2 mice and their corresponding wild-type mice...
March 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28324318/botulinum-neurotoxin-type-a-for-the-treatment-of-pain-not-just-in-migraine-and-trigeminal-neuralgia
#2
Giorgio Sandrini, Roberto De Icco, Cristina Tassorelli, Nicola Smania, Stefano Tamburin
BACKGROUND: Despite their huge epidemiological impact, primary headaches, trigeminal neuralgia and other chronic pain conditions still receive suboptimal medical approach, even in developed countries. The limited efficacy of current pain-killers and prophylactic treatments stands among the main reasons for this phenomenon. Botulinum neurotoxin (BoNT) represents a well-established and licensed treatment for chronic migraine, but also an emerging treatment for other types of primary headache, trigeminal neuralgia, neuropathic pain, and an increasing number of pain conditions...
December 2017: Journal of Headache and Pain
https://www.readbyqxmd.com/read/28323873/a-three-monoclonal-antibody-combination-potently-neutralizes-multiple-botulinum-neurotoxin-serotype-f-subtypes
#3
Yongfeng Fan, Consuelo Garcia-Rodriguez, Jianlong Lou, Weihua Wen, Fraser Conrad, Wenwu Zhai, Theresa J Smith, Leonard A Smith, James D Marks
Human botulism is primarily caused by botulinum neurotoxin (BoNT) serotypes A, B and E, with around 1% caused by serotype F (BoNT/F). BoNT/F comprises at least seven different subtypes with the amino acid sequence difference between subtypes as high as 36%. The sequence differences present a significant challenge for generating monoclonal antibodies (mAbs) that can bind, detect and neutralize all BoNT/F subtypes. We used repertoire cloning of immune mouse antibody variable (V) regions and yeast display to generate a panel of 33 lead single chain Fv (scFv) mAbs that bound one or more BoNT/F subtypes with a median equilibrium dissociation constant (KD) of 4...
2017: PloS One
https://www.readbyqxmd.com/read/28321600/post-6-ohda-lesion-exposure-to-stress-affects-neurotrophic-factor-expression-and-aggravates-motor-impairment
#4
Phumzile Nomfundo Ngema, Musa Vuyisile Mabandla
Chronic exposure to stress amplifies locomotor deficits and exacerbates dopamine neuron loss in an animal model for Parkinson's disease. The release of neurotrophic factors such as glial cell-line derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) following neuronal injury attenuates exacerbated degeneration of these neurons. In this study, the neurotoxin 6-hydroxydopamine (6-OHDA) was injected unilaterally into the medial forebrain bundle of male Sprague Dawley rats. A subset of these rats was subjected to post-lesion restraint stress after which the effect of exposure to stress on locomotor activity (forelimb akinesia test), neurotrophic factor (GDNF and NT-3) and corticosterone concentration was assessed...
March 20, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28320278/cooperative-synthesis-of-dopamine-in-rat-mediobasal-hypothalamus-as-a-compensatory-mechanism-in-hyperprolactinemia
#5
A U Kurina, T S Pronina, L K Dilmukhametova, G V Maleev, M V Ugrumov
Dopamine (DA), synthesized in the mediobasal hypothalamus by dopaminergic neurons containing two enzymes of DA synthesis - tyrosine hydroxylase and decarboxylase of aromatic L-amino acids, or by monoenzymatic non-dopaminergic neurons containing one DA synthesis enzyme in cooperation, is known to have an inhibitory effect on prolactin secretion. Deterioration of this inhibitory control leads to an increase in prolactin concentration in the blood and to the development of hyperprolactinemia syndrome. In a rat model of hyperprolactinemia induced by administration of a neurotoxin causing degeneration of dopaminergic and noradrenergic neurons, the level of DA first decreases, leading to an increase in prolactin level (decompensation stage), while later both levels are restored to normal (compensation stage)...
March 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28320274/brain-mitochondrial-subproteome-of-rpn10-binding-proteins-and-its-changes-induced-by-the-neurotoxin-mptp-and-the-neuroprotector-isatin
#6
A E Medvedev, O A Buneeva, A T Kopylov, O V Tikhonova, M V Medvedeva, L N Nerobkova, I G Kapitsa, V G Zgoda
Mitochondria play an important role in molecular mechanisms of neuroplasticity, adaptive changes of the brain that occur in the structure and function of its cells in response to altered physiological conditions or development of pathological disorders. Mitochondria are a crucial target for actions of neurotoxins, causing symptoms of Parkinson's disease in various experimental animal models, and also neuroprotectors. Good evidence exists in the literature that mitochondrial dysfunction induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) influences functioning of the ubiquitin-proteasomal system (UPS) responsible for selective proteolytic degradation of proteins from various intracellular compartments (including mitochondria), and neuroprotective effects of certain antiparkinsonian agents (monoamine oxidase inhibitors) may be associated with their effects on UPS...
March 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28315357/therapeutic-potential-of-krait-venom
#7
Antony Gomes, Partha Pratim Saha, Shamik Bhattacharya, Sourav Ghosh, Aparna Gomes
Kraits belong to Elapideae and are widely distributed in East and South-East Asian countries. Krait venom possesses neurotoxins, membrane toxins, cardiotoxins, three finger toxins, metalloproteinases, cholinesterases, L-amino acid oxidases and serine proteases. The therapeutic potential of krait venom in pathophysiological conditions such as microbial and parasitic infections, cancer, arthritis, inflammation and blood coagulation disorder is discussed in this review. More intensive new research ventures are required to establish the therapeutic potential of krait venom in complex and emerging diseases...
March 14, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28306751/peptidomic-and-transcriptomic-profiling-of-four-distinct-spider-venoms
#8
Vera Oldrati, Dominique Koua, Pierre-Marie Allard, Nicolas Hulo, Miriam Arrell, Wolfgang Nentwig, Frédérique Lisacek, Jean-Luc Wolfender, Lucia Kuhn-Nentwig, Reto Stöcklin
Venom based research is exploited to find novel candidates for the development of innovative pharmacological tools, drug candidates and new ingredients for cosmetic and agrochemical industries. Moreover, venomics, as a well-established approach in systems biology, helps to elucidate the genetic mechanisms of the production of such a great molecular biodiversity. Today the advances made in the proteomics, transcriptomics and bioinformatics fields, favor venomics, allowing the in depth study of complex matrices and the elucidation even of minor compounds present in minute biological samples...
2017: PloS One
https://www.readbyqxmd.com/read/28303250/predicting-presynaptic-and-postsynaptic-neurotoxins-by-developing-feature-selection-technique
#9
Hua Tang, Yunchun Yang, Chunmei Zhang, Rong Chen, Po Huang, Chenggang Duan, Ping Zou
Presynaptic and postsynaptic neurotoxins are proteins which act at the presynaptic and postsynaptic membrane. Correctly predicting presynaptic and postsynaptic neurotoxins will provide important clues for drug-target discovery and drug design. In this study, we developed a theoretical method to discriminate presynaptic neurotoxins from postsynaptic neurotoxins. A strict and objective benchmark dataset was constructed to train and test our proposed model. The dipeptide composition was used to formulate neurotoxin samples...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28299552/the-history-of-botulinum-toxin-from-poison-to-beauty
#10
Katlein França, Anagha Kumar, Massimo Fioranelli, Torello Lotti, Michael Tirant, Maria Grazia Roccia
Botulinum toxin, also called the "miracle toxin," is a neurotoxin produced by the bacteria Clostridium botulinum. It is known to block nerve signals that contract muscles resulting in a temporary paralysis of the muscles. Toxins type A and B have been extensively studied and utilized in the realm of beauty and cosmetology. Initially, the toxin gained popularity as a disease-causing "poison". It was only later that it found its way to becoming a must have in modern aesthetic practice. Today, this wonder toxin has proven to be an apt and convenient option in the field of anti-aging medicine...
March 15, 2017: Wiener Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28296078/botulinum-neurotoxin-type-b-uses-a-distinct-entry-pathway-mediated-by-cdc42-into-intestinal-cells-versus-neuronal-cells
#11
Chloé Connan, Marie Voillequin, Carolina Varela Chavez, Christelle Mazuet, Christian Leveque, Sandrine Vitry, Alain Vandewalle, Michel R Popoff
Botulinum neurotoxins (BoNTs) are responsible for severe flaccid paralysis by inhibiting the release of acetylcholine at the neuromuscular junctions. BoNT/B most often induces mild forms of botulism with predominant dysautonomic symptoms. In food borne botulism and botulism by intestinal colonization such as infant botulism, which are the most frequent naturally acquired forms of botulism, the digestive tract is the main entry route of BoNTs into the organism. We previously showed that BoNT/B translocates through mouse intestinal barrier by an endocytosis-dependent mechanism and subsequently targets neuronal cells, mainly cholinergic neurons, in the intestinal mucosa and musculosa...
March 11, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28295026/neuronal-entry-and-high-neurotoxicity-of-botulinum-neurotoxin-a-require-its-n-terminal-binding-sub-domain
#12
Jiafu Wang, Jianghui Meng, Marc Nugent, Minhong Tang, J Oliver Dolly
Botulinum neurotoxins (BoNTs) are the most toxic proteins known, due to inhibiting the neuronal release of acetylcholine and causing flaccid paralysis. Most BoNT serotypes target neurons by binding to synaptic vesicle proteins and gangliosides via a C-terminal binding sub-domain (HCC). However, the role of their conserved N-terminal sub-domain (HCN) has not been established. Herein, we created a mutant form of recombinant BoNT/A lacking HCN (rAΔHCN) and showed that the lethality of this mutant is reduced 3...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28294337/copper-increases-the-ability-of-6-hydroxydopamine-to-generate-oxidative-stress-and-the-ability-of-ascorbate-and-glutathione-to-potentiate-this-effect-potential-implications-in-parkinson-s-disease
#13
Antón Cruces-Sande, Estefanía Méndez-Álvarez, Ramón Soto-Otero
Copper is an essential metal for the function of many proteins related to important cellular reactions and also involved in the synaptic transmission. Although there are several mechanisms involved in copper homeostasis, a dysregulation in this process can result in serious neurological consequences, including degeneration of dopaminergic neurons. 6-Hydroxydopamine is a dopaminergic neurotoxin mainly used in experimental models of Parkinson's disease, whose neurotoxicity has been related to its ability to generate free radicals...
March 14, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28293899/effects-of-atomoxetine-on-attention-in-wistar-rats-treated-with-the-neurotoxin-n-2-chloroethyl-n-ethyl-2-bromobenzylamine-dsp4
#14
Joachim Hauser, Andreas Reissmann, Thomas-A Sontag, Oliver Tucha, Klaus W Lange
The aim of the present study was to assess the effects of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), which allows a depletion of noradrenergic terminals in a dose-dependent manner, on attention in rats as measured using the five-choice serial-reaction time task (5CSRTT). In addition, we investigated whether the effects of DSP4 treatment can be reversed by atomoxetine. Atomoxetine is a selective noradrenaline reuptake inhibitor and has been shown to be effective in the treatment of attention deficit hyperactivity disorder...
March 14, 2017: Attention Deficit and Hyperactivity Disorders
https://www.readbyqxmd.com/read/28289514/modern-trends-in-animal-venom-research-omics-and-nanomaterials
#15
EDITORIAL
Yuri N Utkin
Animal venom research is a specialized investigation field, in which a number of different methods are used and this array is constantly expanding. Thus, recently emerged omics and nanotechnologies have already been successfully applied to venom research. Animal venoms have been studied for quite a long time. The traditional reductionist approach has been to isolate individual toxins and then study their structure and function. Unfortunately, the characterization of the venom as a whole system and its multiple effects on an entire organism were not possible until recent times...
February 26, 2017: World Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28288867/moderate-traumatic-brain-injury-increases-the-vulnerability-to-neurotoxicity-induced-by-systemic-administration-of-6-hydroxydopamine-in-mice
#16
Paulo Alexandre de Oliveira, Juliana Ben, Filipe Carvalho Matheus, Marcelo Liborio Schwarzbold, Eduardo Luiz Gasnhar Moreira, Daniel Rial, Roger Walz, Rui Daniel Prediger
Moderate traumatic brain injury (TBI) might increase the vulnerability to neuronal neurodegeneration, but the basis of such selective neuronal susceptibility has remained elusive. In keeping with the disruption of the blood-brain barrier (BBB) caused by TBI, changes in BBB permeability following brain injury could facilitate the access of xenobiotics into the brain. To test this hypothesis, here we evaluated whether TBI would increase the susceptibility of nigrostriatal dopaminergic fibers to the systemic administration of 6-hydroxydopamine (6-OHDA), a classic neurotoxin used to trigger a PD-like phenotype in mice, but that in normal conditions is unable to cross the BBB...
March 10, 2017: Brain Research
https://www.readbyqxmd.com/read/28287384/effects-of-potassium-adsorption-filters-on-the-removal-of-ammonia-from-blood-products
#17
Hiroshi Fujita, Yoko Shiotani, Yuko Takada, Shigeko Nishimura
BACKGROUND: Although ammonia in plasma does not usually pass through the blood-brain barrier (BBB), in cases of traumatic brain injury it may do so, acting as a neurotoxin on the brain. Excess intake of ammonia should be restricted in conditions involving BBB breakdown, such as traumatic brain injury. Washing is a method to remove ammonia from blood products, but fresh-frozen plasma and albumin products cannot be washed. A potassium adsorption filter (PAF) can remove not only potassium, but also ammonia from red blood cell solutions...
March 1, 2017: Blood Transfusion, Trasfusione del Sangue
https://www.readbyqxmd.com/read/28286494/clinical-practice-evidence-based-recommendations-for-the-treatment-of-cervical-dystonia-with-botulinum-toxin
#18
REVIEW
Maria Fiorella Contarino, Joost Van Den Dool, Yacov Balash, Kailash Bhatia, Nir Giladi, Johannes H Koelman, Annemette Lokkegaard, Maria J Marti, Miranda Postma, Maja Relja, Matej Skorvanek, Johannes D Speelman, Evelien Zoons, Joaquim J Ferreira, Marie Vidailhet, Alberto Albanese, Marina A J Tijssen
Cervical dystonia (CD) is the most frequent form of focal dystonia. Symptoms often result in pain and functional disability. Local injections of botulinum neurotoxin are currently the treatment of choice for CD. Although this treatment has proven effective and is widely applied worldwide, many issues still remain open in the clinical practice. We performed a systematic review of the literature on botulinum toxin treatment for CD based on a question-oriented approach, with the aim to provide practical recommendations for the treating clinicians...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28285345/on-the-role-of-dt-diaphorase-inhibition-in-aminochrome-induced-neurotoxicity-in-vivo
#19
Andrea Herrera-Soto, Gabriela Díaz-Veliz, Sergio Mora, Patricia Muñoz, Pablo Henny, Harry W M Steinbusch, Juan Segura-Aguilar
Dopamine oxidation in the pathway leading to neuromelanin formation generates the ortho-quinone aminochrome, which is potentially neurotoxic but normally rapidly converted by DT-diaphorase to nontoxic leukoaminochrome. However, when administered exogenously into rat striatum, aminochrome is able to produce damage to dopaminergic neurons. Because of a recent report that substantia nigra pars compacta (SNpc) tyrosine hydroxylase (T-OH) levels were unaltered by aminochrome when there was cell shrinkage of dopaminergic neurons along with a reduction in striatal dopamine release, the following study was conducted to more accurately determine the role of DT-diaphorase in aminochrome neurotoxicity...
March 11, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28282915/implementing-the-bruker-maldi-biotyper-in-the-public-health-laboratory-for-c-botulinum-neurotoxin-detection
#20
Michael J Perry, Dominick A Centurioni, Stephen W Davis, George E Hannett, Kimberlee A Musser, Christina T Egan
Currently, the gold standard method for active botulinum neurotoxin (BoNT) detection is the mouse bioassay (MBA). A Centers for Disease Control and Prevention-developed mass spectrometry (MS)-based assay that detects active BoNT was successfully validated and implemented in a public health laboratory in clinical matrices using the Bruker MALDI-TOF MS (Matrix-assisted laser desorption ionization-time of flight mass spectrometry) Biotyper. For the first time, a direct comparison with the MBA was performed to determine MS-based assay sensitivity using the Bruker MALDI Biotyper...
March 9, 2017: Toxins
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