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https://www.readbyqxmd.com/read/28237716/clostridium-perfringens-epsilon-toxin-induces-permanent-neuronal-degeneration-and-behavioral-changes
#1
Winston E Morris, Jorge Goldstein, Leandro M Redondo, Adriana Cangelosi, Patricia Geoghegan, Marcela Brocco, Fabián C Loidl, Mariano E Fernandez-Miyakawa
Clostridium perfringens epsilon toxin (ETX), the most potent toxin produced by this bacteria, plays a key role in the pathogenesis of enterotoxaemia in ruminants, causing brain edema and encephalomalacia. Studies of animals suffering from ETX intoxication describe severe neurological disorders that are thought to be the result of vasogenic brain edemas and indirect neuronal toxicity, killing oligodendrocytes but not astrocytes, microglia, or neurons in vitro. In this study, by means of intravenous and intracerebroventricular delivery of sub-lethal concentrations of ETX, the histological and ultrastructural changes of the brain were studied in rats and mice...
February 22, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28231291/osteosarcoma-cell-proliferation-and-survival-requires-mglur5-receptor-activity-and-is-blocked-by-riluzole
#2
Sally Liao, Yuleisy Ruiz, Hira Gulzar, Zarina Yelskaya, Lyes Ait Taouit, Murielle Houssou, Trisha Jaikaran, Yuriy Schvarts, Kristina Kozlitina, Upal Basu-Roy, Alka Mansukhani, Shahana S Mahajan
Osteosarcomas are malignant tumors of bone, most commonly seen in children and adolescents. Despite advances in modern medicine, the poor survival rate of metastatic osteosarcoma has not improved in two decades. In the present study we have investigated the effect of Riluzole on a human and mouse metastatic osteosarcoma cells. We show that LM7 cells secrete glutamate in the media and that mGluR5 receptors are required for the proliferation of LM7 cells. Riluzole, which is known to inhibit glutamate release, inhibits proliferation, induces apoptosis and prevents migration of LM7 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28197100/rho-kinase-inhibition-with-fasudil-in-the-sod1-g93a-mouse-model-of-amyotrophic-lateral-sclerosis-symptomatic-treatment-potential-after-disease-onset
#3
René Günther, Alexander Balck, Jan C Koch, Tobias Nientiedt, Michael Sereda, Mathias Bähr, Paul Lingor, Lars Tönges
Despite an improved understanding of the genetic background and the pathomechanisms of amyotrophic lateral sclerosis (ALS) no novel disease-modifying therapies have been successfully implemented in clinical routine. Riluzole still remains the only clinically approved substance in human ALS treatment with limited efficacy. We have previously identified pharmacological rho kinase (ROCK) inhibitors as orally applicable substances in SOD1.G93A transgenic ALS mice (SOD1(G93A)), which are able to extend survival time and improve motor function after presymptomatic treatment...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28194724/ketamine-and-beyond-investigations-into-the-potential-of-glutamatergic-agents-to-treat-depression
#4
REVIEW
Marc S Lener, Bashkim Kadriu, Carlos A Zarate
Clinical and preclinical studies suggest that dysfunction of the glutamatergic system is implicated in mood disorders such as major depressive disorder and bipolar depression. In clinical studies of individuals with major depressive disorder and bipolar depression, rapid reductions in depressive symptoms have been observed in response to subanesthetic-dose ketamine, an agent whose mechanism of action involves the modulation of glutamatergic signaling. The findings from these studies have prompted the repurposing and/or development of other glutamatergic modulators for antidepressant efficacy, both as monotherapy or as an adjunct to conventional monoaminergic antidepressants...
February 14, 2017: Drugs
https://www.readbyqxmd.com/read/28193882/neuronal-hyperexcitability-in-a-mouse-model-of-scn8a-epileptic-encephalopathy
#5
Luis F Lopez-Santiago, Yukun Yuan, Jacy L Wagnon, Jacob M Hull, Chad R Frasier, Heather A O'Malley, Miriam H Meisler, Lori L Isom
Patients with early infantile epileptic encephalopathy (EIEE) experience severe seizures and cognitive impairment and are at increased risk for sudden unexpected death in epilepsy (SUDEP). EIEE13 [Online Mendelian Inheritance in Man (OMIM) # 614558] is caused by de novo missense mutations in the voltage-gated sodium channel gene SCN8A Here, we investigated the neuronal phenotype of a mouse model expressing the gain-of-function SCN8A patient mutation, p.Asn1768Asp (Nav1.6-N1768D). Our results revealed regional and neuronal subtype specificity in the effects of the N1768D mutation...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28175531/329%C3%A2-efficacy-and-safety-of-riluzole-in-acute-spinal-cord-injury-rationale-and-design-of-aospine-phase-iii-multicenter-double-blinded-randomized-controlled-trial-riscis
#6
Michael G Fehlings, Branko Kopjar, Robert G Grossman
No abstract text is available yet for this article.
August 1, 2016: Neurosurgery
https://www.readbyqxmd.com/read/28175502/321%C3%A2-development-of-intrathecal-riluzole-a-new-route-of-administration-for-the-treatment-of-amyotrophic-lateral-sclerosis-patients
#7
Juanmarco Gutierrez, Thais Federici, Bethany Peterson, Ray Bartus, Alexandre Betourne, Nicholas M Boulis
No abstract text is available yet for this article.
August 1, 2016: Neurosurgery
https://www.readbyqxmd.com/read/28164143/a-predictive-model-for-prognosis-in-motor-neuron-disease
#8
Mirian Conceicao Moura, Luiz Augusto Casulari, Maria Rita Carvalho Garbi Novaes
OBJECTIVES: There have been attempts to establish biomarkers for motor neuron disease, without success. The study aim to seek possible markers to be used in the clinical routine evaluation, to optimize timing for palliative interventions. METHODS: A cohort study evaluated clinical, respiratory and neurophysiological variables every 3-4 months across 20 months in 101 patients with motor neuron disease using riluzole. Primary endpoint was death or tracheostomy. The most significant parameters in cox regression analysis created a predictive model...
December 2016: Journal of Neurological Disorders
https://www.readbyqxmd.com/read/28162597/-355-riluzole-actions-on-sk-channels-in-the-amygdala-in-acute-arthritic-and-chronic-neuropathic-pain
#9
J Thompson, G Ji, V Neugebauer
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28148632/serum-neurofilament-is-associated-with-progression-of-brain-atrophy-and-disability-in-early-ms
#10
Jens Kuhle, Bardia Nourbakhsh, Donna Grant, Steve Morant, Christian Barro, Özgür Yaldizli, Daniel Pelletier, Gavin Giovannoni, Emmanuelle Waubant, Sharmilee Gnanapavan
OBJECTIVE: To investigate a potential effect of riluzole on serum neurofilaments (Nf) compared to placebo and the relationship between longitudinal clinical and MRI outcomes and serum Nf levels. METHODS: Serum samples were obtained from participants enrolled in a randomized double-blind trial of neuroprotection with riluzole vs placebo as an add-on to weekly interferon-β (IFN-β)-1a IM initiated 3 months after randomization. Nf measurements were performed by ELISA and electrochemiluminescence immunoassay...
February 1, 2017: Neurology
https://www.readbyqxmd.com/read/28129947/target-intestinal-microbiota-to-alleviate-disease-progression-in-amyotrophic-lateral-sclerosis
#11
Yong-Guo Zhang, Shaoping Wu, Jianxun Yi, Yinglin Xia, Dapeng Jin, Jingsong Zhou, Jun Sun
PURPOSE: Emerging evidence has demonstrated that gut microbiome plays essential roles in the pathogenesis of human diseases in distal organs. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Treatment with the only drug approved by the US Food and Drug Administration for use in ALS, riluzole, extends a patient׳s life span by only a few months. Thus, there is an urgent need to develop novel interventions that for alleviate disease progression and improve quality of life in patients with ALS...
February 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28095499/treatment-with-riluzole-restores-normal-control-of-soleus-and-extensor-digitorum-longus-muscles-during-locomotion-in-adult-rats-after-sciatic-nerve-crush-at-birth
#12
Wojciech Zmysłowski, Anna M Cabaj, Urszula Sławińska
The effects of sciatic nerve crush (SNC) and treatment with Riluzole on muscle activity during unrestrained locomotion were identified in an animal model by analysis of the EMG activity recorded from soleus (Sol) and extensor digitorum longus (EDL) muscles of both hindlimbs; in intact rats (IN) and in groups of rats treated for 14 days with saline (S) or Riluzole (R) after right limb nerve crush at the 1st (1S and 1R) or 2nd (2S and 2R) day after birth. Changes in the locomotor pattern of EMG activity were correlated with the numbers of survived motor units (MUs) identified in investigated muscles...
2017: PloS One
https://www.readbyqxmd.com/read/28072907/symptomatic-treatments-for-amyotrophic-lateral-sclerosis-motor-neuron-disease
#13
REVIEW
Louisa Ng, Fary Khan, Carolyn A Young, Mary Galea
BACKGROUND: Motor neuron disease (MND), which is also known as amyotrophic lateral sclerosis (ALS), causes a wide range of symptoms but the evidence base for the effectiveness of the symptomatic treatment therapies is limited. OBJECTIVES: To summarise the evidence from Cochrane Systematic Reviews of all symptomatic treatments for MND. METHODS: We searched the Cochrane Database of Systematic Reviews (CDSR) on 15 November 2016 for systematic reviews of symptomatic treatments for MND...
January 10, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28060747/25-hydroxycholesterol-is-involved-in-the-pathogenesis-of-amyotrophic-lateral-sclerosis
#14
Sung-Min Kim, Min-Young Noh, Heejaung Kim, So-Young Cheon, Kang Mi Lee, Jaeick Lee, Eunju Cha, Kyung Seok Park, Kwang-Woo Lee, Jung-Joon Sung, Seung Hyun Kim
This study aimed to evaluate the levels of three major hydroxycholesterols (24-, 25-, and 27-hydroxycholesterols) in the serum and cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS), as well as to show their role in the pathogenesis of ALS experimental models. The level of 25-hydroxycholesterol were higher in untreated ALS patients (n = 30) than in controls without ALS (n = 33) and ALS patients treated with riluzole (n = 9) both in their serum and CSF. The level of 25-hydroxycholesterol in the serum of ALS patients were significantly associated with their disease severity and rate of progression...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28053507/riluzole-5-mg-ml-oral-suspension-for-optimized-drug-delivery-in-amyotrophic-lateral-sclerosis
#15
Ann Margaret Dyer, Alan Smith
The aim of the present work is to extensively evaluate the pharmaceutical attributes of currently available riluzole presentations. The article describes the limitations and risks associated with the administration of crushed tablets, including the potential for inaccurate dosing and reduced rate of absorption when riluzole is administered with high-fat foods, and the advantages that a recently approved innovative oral liquid form of riluzole confers on amyotrophic lateral sclerosis (ALS) patients. The article further evaluates the patented and innovative controlled flocculation technology used in the pseudoplastic suspension formulation to reduce the oral anesthesia seen with crushed tablets, resulting in optimized drug delivery for riluzole...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28049095/riluzole-ameliorates-learning-and-memory-deficits-in-a%C3%AE-25-35-induced-rat-model-of-alzheimer-s-disease-and-is-independent-of-cholinoceptor-activation
#16
Zahra Mokhtari, Tourandokht Baluchnejadmojarad, Farnaz Nikbakht, Monireh Mansouri, Mehrdad Roghani
Alzheimer's disease (AD) is a major global public health concern and social care problem that is associated with learning, memory, and cognitive deficits. Riluzole is a glutamate modulator which has shown to improve memory performance in aged rats and may be of benefit in Alzheimer's disease. In the present study, its beneficial effect on attenuation of learning and memory deficits in Aβ25-35-induced rat model of AD was assessed. Riluzole administration at a dose of 10mg/kg/day p.o. improved spatial memory in Morris water maze and retention and recall in passive avoidance task and its protective effect was not neutralized following intracerebroventricular microinjection of muscarinic or nicotinic receptor antagonists...
March 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28049029/glutamate-transporter-type-3-participates-in-maintaining-morphine-induced-conditioned-place-preference
#17
Li Wan, Jiangjiang Bi, Jun Li, Zhiyi Zuo
Glutamate transporters (EAAT) have been implicated in the drug addiction behavior. We determined whether EAAT type 3 (EAAT3) played a role in morphine addiction. Six- to eight-week-old EAAT3 knockout (EAAT3(-/-)) mice and their wild-type littermates received 3 intraperitoneal injections of 10mg/kg morphine, each on an alternative day, to induce conditioned place preference (CPP). Two days after the place preference returned to baseline, mice received 2.5mg/kg morphine to induce reinstatement. Some mice received intraperitoneal injection of 4mg/kg riluzole, an EAAT activator, 30min before morphine or saline injection...
March 6, 2017: Neuroscience
https://www.readbyqxmd.com/read/28000730/an-acridine-derivative-4-5-bis-n-carboxy-methyl-imidazolium-methyl-acridine-dibromide-shows-anti-tdp-43-aggregation-effect-in-als-disease-models
#18
Archana Prasad, Gembali Raju, Vishwanath Sivalingam, Amandeep Girdhar, Meenakshi Verma, Abhishek Vats, Vibha Taneja, Ganesan Prabusankar, Basant K Patel
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with aggregation of TAR DNA-binding protein-43 (TDP-43) in neuronal cells and manifests as motor neuron dysfunction &muscle atrophy. The carboxyl-terminal prion-like domain of TDP-43 can aggregate in vitro into toxic β-sheet rich amyloid-like structures. So far, treatment options for ALS are very limited and Riluzole, which targets glutamate receptors, is the only but highly ineffective drug. Therefore, great interest exists in developing molecules for ALS treatment...
December 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27975196/economic-studies-in-motor-neurone-disease-a-systematic-methodological-review
#19
REVIEW
Alan Moore, Carolyn A Young, Dyfrig A Hughes
BACKGROUND: Motor neurone disease (MND) is a devastating condition which greatly diminishes patients' quality of life and limits life expectancy. Health technology appraisals of future interventions in MND need robust data on costs and utilities. Existing economic evaluations have been noted to be limited and fraught with challenges. OBJECTIVE: The aim of this study was to identify and critique methodological aspects of all published economic evaluations, cost studies, and utility studies in MND...
December 14, 2016: PharmacoEconomics
https://www.readbyqxmd.com/read/27960523/the-effect-of-cage-shape-on-nanoparticle-based-drug-carriers-anticancer-drug-release-and-efficacy-via-receptor-blockade-using-dextran-coated-iron-oxide-nanocages
#20
Sham Rampersaud, Justin Fang, Zengyan Wei, Kristina Fabijanic, Stefan Silver, Trisha Jaikaran, Yuleisy Ruiz, Murielle Houssou, Zhiwei Yin, Shengping Zheng, Ayako Hashimoto, Ayuko Hoshino, David Lyden, Shahana Mahajan, Hiroshi Matsui
Although a range of nanoparticles have been developed as drug delivery systems in cancer therapeutics, this approach faces several important challenges concerning nanocarrier circulation, clearance, and penetration. The impact of reducing nanoparticle size on penetration through leaky blood vessels around tumor microenvironments via enhanced permeability and retention (EPR) effect has been extensively examined. Recent research has also investigated the effect of nanoparticle shape on circulation and target binding affinity...
December 14, 2016: Nano Letters
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