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Tomohiro Yamashita, Shota Yamamoto, Jiaming Zhang, Miho Kometani, Daisuke Tomiyama, Keita Kohno, Hidetoshi Tozaki-Saitoh, Kazuhide Inoue, Makoto Tsuda
P2X4 receptors (P2X4R) are a family of ATP-gated non-selective cation channels. We previously demonstrated that activation of P2X4R in spinal microglia is crucial for neuropathic pain, a highly debilitating chronic pain condition, suggesting that P2X4R is a potential therapeutic target for treating neuropathic pain. Thus, the identification of a compound that has a potent inhibitory effect on P2X4R is an important clinical challenge. In the present study, we screened a chemical library of clinically approved drugs and show for the first time that duloxetine, a serotonin and noradrenaline reuptake inhibitor, has an inhibitory effect on rodent and human P2X4R...
2016: PloS One
Meta N Eek, Kate Himmelmann
Spasticity and muscle weakness is common in children with cerebral palsy (CP). Spasticity can be treated with botulinum neurotoxin-A (BoNT-A), but this drug has also been reported to induce muscle weakness. Our purpose was to describe the effect on muscle strength in the lower extremities after BoNT-A injections in children with CP. A secondary aim was to relate the effect of BoNT-A to gait pattern and range of motion. Twenty children with spastic CP were included in the study, 8 girls and 12 boys (mean age 7...
2016: Frontiers in Human Neuroscience
Ayush Attery, Janendra K Batra
Ribonuclease A family is a group of proteins having similar structures and catalytic mechanism but different functions. Human eosinophil granules contain two ribonucleases belonging to the RNase A family, eosinophil cationic protein (ECP) and eosinophil derived neurotoxin (EDN). In mouse, 15 orthologs of EDN and ECP, called mouse eosinophil associated ribonucleases (mEARs) have been reported which are expressed under different pathophysiological conditions. In this study, we have characterized mEAR2, mEAR5, mEAR7 and mEAR11, and compared them with ECP for their catalytic, cytotoxic, antibacterial and antiparasitic activities...
October 17, 2016: International Journal of Biological Macromolecules
Domenico Intiso, Andrea Santamato, Filomena Di Rienzo
OBJECTIVE: To investigate whether electrical stimulation (ES) as an adjunct to BTX-A boosts botulinum activity and whether the combined therapeutic procedure is more effective than BTX-A alone in reducing spasticity in adult subjects. DATA SOURCES: A search was conducted in PubMed, EMBASE, Cochrane Central Register, and CINAHL from January 1966 to January 2016. STUDY SELECTION: Only randomized controlled studies (RCT) involving the combination of BTX-A and ES were considered...
October 21, 2016: Disability and Rehabilitation
Anjana Silva, Wayne C Hodgson, Geoffrey K Isbister
There is limited information on the cross-neutralisation of neurotoxic venoms with antivenoms. Cross-neutralisation of the in vitro neurotoxicity of four Asian and four Australian snake venoms, four post-synaptic neurotoxins (α-bungarotoxin, α-elapitoxin-Nk2a, α-elapitoxin-Ppr1 and α-scutoxin; 100 nM) and one pre-synaptic neurotoxin (taipoxin; 100 nM) was studied with five antivenoms: Thai cobra antivenom (TCAV), death adder antivenom (DAAV), Thai neuro polyvalent antivenom (TNPAV), Indian Polyvalent antivenom (IPAV) and Australian polyvalent antivenom (APAV)...
October 18, 2016: Toxins
G Magistro, C G Stief, C Gratzke
Novel minimally invasive treatment options for the management of male lower urinary tract symptoms (LUTS) due to bladder outlet obstruction (BOO) aim to provide equal efficacy compared to standard techniques with a more favourable safety profile. The preservation of all aspects of male sexual function including antegrade ejaculation is increasingly important to patients. It should be ideally performed in an outpatient setting under local anesthesia to assure a short recovery time. Novel injectables for intraprostatic application (botulinum neurotoxin A, NX-1207, PRX302) have emerged and first phase III results could not confirm the promising initial data...
October 19, 2016: Der Urologe. Ausg. A
Haiying Shen, Kiyoon Kim, Yoojung Oh, Kyung Sik Yoon, Hyung Hwan Baik, Sung Soo Kim, Joohun Ha, Insug Kang, Wonchae Choe
β-N-methylamino-L-alanine (BMAA) is a neurotoxin that is closely associated with the incidence of amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease. In cultured neuronal cells, BMAA notably induces the upregulation of endoplasmic reticulum (ER) chaperons and activates the unfolded protein response (UPR) receptor pathways of protein kinase RNA‑like endoplasmic reticulum kinase, inositol‑requiring kinase 1 and transcription factor 6. The ER stress‑specific protein CCAAT/‑enhancer‑binding protein homologous protein (CHOP) affords pro‑apoptotic responses that cause mitochondrial damage and caspase activation...
October 5, 2016: Molecular Medicine Reports
Aileen I Pogue, Walter J Lukiw
No abstract text is available yet for this article.
August 2016: Journal of Alzheimer's Disease and Parkinsonism
Oliver G Weingart, Martin J Loessner
Botulinum neurotoxins (BoNT) are the most toxic substances known, and their neurotoxic properties and paralysing effects are exploited for medical treatment of a wide spectrum of disorders. To accurately quantify the potency of a pharmaceutical BoNT preparation, its physiological key activities (binding to membrane receptor, translocation, and proteolytic degradation of SNARE proteins) need to be determined. To date, this was only possible using animal models, or, to a limited extent, cell-based assays. We here report a novel in vitro system for BoNT/B analysis, based on nerve-cell mimicking liposomes presenting motoneuronal membrane receptors required for BoNT binding...
October 12, 2016: Toxicology and Applied Pharmacology
Kai-Chih Hung, Hui-Ju Huang, Yi-Ting Wang, Anya Maan-Yuh Lin
ETHNOPHARMACOLOGICAL RELEVANCE: Neuroinflammation, oxidative stress, and protein aggregation form a vicious cycle in the pathophysiology of Parkinson's disease (PD); activated microglia is the main location of neuroinflammation. A Chinese medicine book, "Shanghan Lun", known as the "Treatises on Cold damage Diseases" has suggested that Scutellaria baicalensis Georgi is effective in treating CNS diseases. The anti-inflammatory mechanisms of baicalein, a phenolic flavonoid in the dried root of Scutellaria baicalensis Georgi, remain to be explored...
October 11, 2016: Journal of Ethnopharmacology
F Vallone, E Vannini, A Cintio, M Caleo, A Di Garbo
Epilepsy is characterized by substantial network rearrangements leading to spontaneous seizures and little is known on how an epileptogenic focus impacts on neural activity in the contralateral hemisphere. Here, we used a model of unilateral epilepsy induced by injection of the synaptic blocker tetanus neurotoxin (TeNT) in the mouse primary visual cortex (V1). Local field potential (LFP) signals were simultaneously recorded from both hemispheres of each mouse in acute phase (peak of toxin action) and chronic condition (completion of TeNT effects)...
September 2016: Physical Review. E
Maria Jenelyn M Alviar, Tom Hale, Monalisa Dungca
BACKGROUND: This is an updated version of the original Cochrane review published in Issue 12, 2011. Phantom limb pain (PLP) is pain that arises in the missing limb after amputation and can be severe, intractable, and disabling. Various medications have been studied in the treatment of phantom pain. There is currently uncertainty in the optimal pharmacologic management of PLP. OBJECTIVES: This review aimed to summarise the evidence of effectiveness of pharmacologic interventions in treating PLP...
October 14, 2016: Cochrane Database of Systematic Reviews
Suraj S Pradhan, Kirstie Salinas, Alexis C Garduno, Jenny U Johansson, Qian Wang, Amy Manning-Bog, Katrin I Andreasson
Inflammation is a ubiquitous factor accompanying normal aging and neurodegeneration, and recent studies indicate a major contribution of inducible cyclooxygenase (COX-2) and its downstream prostaglandin signaling pathways in modulating neuroinflammatory responses and neuronal function. We have previously shown that the prostaglandin PGE2 receptor EP4 suppresses innate immune responses in models of systemic inflammation. Here we investigated the role of the EP4 receptor in models of Parkinson's disease (PD)...
October 12, 2016: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Flora Lucena, Vanessa Foletto, Lucas Zanon Mascarin, Carlos Rogério Tonussi
AIMS: Rheumatoid arthritis brings great burdens to the patients. In addition to the highly expensive treatment, they are commonly associated with severe side-effects. In such context, the research for safe and affordable treatments is needed. MAIN METHODS: Arthritis was induced by CFA (0.5mg/mL) in female wistar rats. Trypsin was given p.o. (2.95mg/kg; 2mL) 24 hs after the intra-articular CFA injection. Articular incapacitation was measured daily by counting the paw elevation time (PET; s) during 1-min periods of stimulated walk, throughout the 7-days after intra-articular CFA injection...
October 8, 2016: Life Sciences
Walter J Lukiw
The human microbiome consists of ~3.8 × 10(13) symbiotic microorganisms that form a highly complex and dynamic ecosystem: the gastrointestinal (GI) tract constitutes the largest repository of the human microbiome by far, and its impact on human neurological health and disease is becoming increasingly appreciated. Bacteroidetes, the largest phylum of Gram-negative bacteria in the GI tract microbiome, while generally beneficial to the host when confined to the GI tract, have potential to secrete a remarkably complex array of pro-inflammatory neurotoxins that include surface lipopolysaccharides (LPSs) and toxic proteolytic peptides...
2016: Frontiers in Microbiology
Mauricio P Cunha, Francis L Pazini, Vicente Lieberknecht, Josiane Budni, Ágatha Oliveira, Júlia M Rosa, Gianni Mancini, Leidiane Mazzardo, André R Colla, Marina C Leite, Adair R S Santos, Daniel F Martins, Andreza F de Bem, Carlos Alberto S Gonçalves, Marcelo Farina, Ana Lúcia S Rodrigues
The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces motor and nonmotor dysfunctions resembling Parkinson's disease (PD); however, studies investigating the effects of 1-methyl-4-phenylpyridinium (MPP(+)), an active oxidative product of MPTP, are scarce. This study investigated the behavioral and striatal neurochemical changes (related to oxidative damage, glial markers, and neurotrophic factors) 24 h after intracerebroventricular administration of MPP(+) (1.8-18 μg/mouse) in C57BL6 mice...
October 8, 2016: Molecular Neurobiology
Paul T Bremer, Song Xue, Kim D Janda
In developing small-molecule inhibitors of botulinum neurotoxin serotype A light chain (BoNT/A LC), substituted picolinic acids were identified. Extensive investigation into the SAR of the picolinic acid scaffold revealed 5-(1-butyl-4-chloro-1H-indol-2-yl)picolinic acid (CBIP), which possessed low micromolar activity against BoNT/A. Kinetic and docking studies demonstrated binding of CBIP to the β-exosite: a largely unexplored site on the LC that holds therapeutic relevance for botulism treatment.
October 13, 2016: Chemical Communications: Chem Comm
Anna Niewiarowska-Sendo, Andrzej Kozik, Ibeth Guevara-Lora
Kinin peptides ubiquitously occur in nervous tissue and participate in inflammatory processes associated with distinct neurological disorders. These substances have also been demonstrated to promote the oxidative stress. On the other hand, the importance of oxidative stress and inflammation has been emphasized in disorders that involve the neurodegenerative processes such as Parkinson's disease (PD). A growing number of reports have demonstrated the increased expression of kinin receptors in neurodegenerative diseases...
2016: Mediators of Inflammation
Yim Ling Mak, Jing Li, Chih-Ning Liu, Shuk Han Cheng, Paul K S Lam, Jinping Cheng, Leo L Chan
Ciguatoxins (CTXs) are natural biotoxins produced by benthic dinoflagellates of the genus Gambierdiscus, which are bioaccumulated and biotransformed along food chains in coral ecosystems. They are neurotoxins that activate voltage-gated sodium channels and disrupt ion conductance in the excitable tissues. Pacific ciguatoxin-1 (P-CTX-1) is the most prevalent and potent CTX congener present in fishes from the Pacific Ocean. In this study, P-CTX-1 was administrated to larval marine medaka (2h post-hatch) via microinjection...
October 1, 2016: Journal of Hazardous Materials
Saak V Ovsepian, Valerie B O'Leary, Vasilis Ntziachristos, J Oliver Dolly
In addition to safeguarding the central nervous system (CNS) from the vast majority of pathogens and toxins, transvascular barriers impose immense challenges to the delivery of beneficial cargo. A few toxins and neurotropic viruses capable of penetrating the brain have proved to be potentially valuable for neuron targeting and enhanced transfer of restorative medicine and therapeutic genes. Here we review molecular concepts and implications of the highly neurotropic tetanus toxin (TeTx) and botulinum neurotoxins (BoNTs) and their ability to infiltrate and migrate throughout neurons...
October 5, 2016: Trends in Molecular Medicine
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