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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
#1
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
#2
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
#3
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
#4
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
#5
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...
December 31, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28049029/glutamate-transporter-type-3-participates-in-maintaining-morphine-induced-conditioned-place-preference
#6
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...
January 1, 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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/27939241/the-anti-als-drug-riluzole-attenuates-pericyte-loss-in-the-diabetic-retinopathy-of-streptozotocin-treated-mice
#10
Jeong A Choi, Yoo-Ri Chung, Hyae-Ran Byun, Hwangseo Park, Jae-Young Koh, Young Hee Yoon
Loss of pericytes, considered an early hallmark of diabetic retinopathy, is thought to involve abnormal activation of protein kinase C (PKC). We previously showed that the anti-amyotrophic lateral sclerosis (ALS) drug riluzole functions as a PKC inhibitor. Here, we examined the effects of riluzole on pathological changes in diabetic retinopathy. Pathological endpoints examined in vivo included the number of pericytes and integrity of retinal vessels in streptozotocin (STZ)-induced diabetic mice. In addition, PKC activation and the induction of monocyte chemotactic protein (MCP1) were assessed in diabetic mice and in human retinal pericytes exposed to advanced glycation end product (AGE) or modified low-density lipoprotein (mLDL)...
December 8, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27923201/synthesis-and-biological-evaluation-of-a-new-class-of-benzothiazines-as-neuroprotective-agents
#11
Alessandra Mancini, Alessia Chelini, Angela Di Capua, Loretta Castelli, Simone Brogi, Marco Paolino, Germano Giuliani, Andrea Cappelli, Maria Frosini, Lorenzo Ricci, Erminia Leonelli, Gianluca Giorgi, Antonio Giordani, Jacopo Magistretti, Maurizio Anzini
Neurodegenerative diseases are disorders related to the degeneration of central neurons that gradually lead to various, severe alterations of cognitive and/or motor functions. Currently, for no such diseases does any pharmacological treatment exist able to arrest its progression. Riluzole (1) is a small molecule able to interfere with multiple cellular and molecular mechanisms of neurodegeneration, and is the only approved treatment of amyotrophic lateral sclerosis (ALS), the progression of which proved to significantly slow, thus increasing somewhat average survival...
November 27, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27922548/methylcobalamin-prevents-mutant-superoxide-dismutase-1-induced-motor-neuron-death-in-vitro
#12
Shunsuke Ito, Yukina Izumi, Tetsuhiro Niidome, Yuichi Ono
Amyotrophic lateral sclerosis (ALS) is an incurable progressive neurodegenerative disorder that causes motor dysfunction. Treatments and drugs that slow progression of ALS have garnered great interest. In the present study, we show that the vitamin B12 analog methylcobalamin (MBL) effectively and dose dependently prevented embryonic stem cell-derived motor neuron death induced by cocultivation with astrocytes expressing mutant human superoxide dismutase-1 (G93A). Moreover, cotreatment of MBL with a conventional ALS drug, riluzole, further enhanced survival of motor neurons in this in-vitro ALS model...
January 18, 2017: Neuroreport
https://www.readbyqxmd.com/read/27894698/dual-effects-of-eugenol-on-the-neuronal-excitability-an-in-vitro-study
#13
Jafar Vatanparast, Samira Khalili, Maryam Naseh
Besides its well-known actions on sensory afferents, eugenol also affects general excitability of the nervous system, but the mechanisms involved in the recent effect, especially through modulation of ion channels, have received much less attention. In this study, we studied the effects of eugenol on the excitability of central neurons of land snail Caucasotachea atrolabiata and tried to elucidate the underlying ionic mechanisms. The lower concentration of eugenol (0.5mM) reversibly reduced the frequency of spontaneous action potentials that was associated with elevation of threshold, reduction of maximum slope of rising phase and prolongation of actin potentials...
November 25, 2016: Neurotoxicology
https://www.readbyqxmd.com/read/27822184/long-term-use-of-riluzole-could-improve-the-prognosis-of-sporadic-amyotrophic-lateral-sclerosis-patients-a-real-world-cohort-study-in-china
#14
Lu Chen, Xiaolu Liu, Lu Tang, Nan Zhang, Dongsheng Fan
Objectives: To investigate the effectiveness of riluzole in a long-term follow-up of cohort with sporadic amyotrophic lateral sclerosis (ALS) in a real-world study. Methods: Patients with ALS between 2007 and 2013 were followed up every 3 months. Survival and tracheotomy were predefined as primary outcome measures. The cumulative defined daily dose (cDDD) of riluzole was estimated. The patients in the riluzole group were classified into 1 of 3 subgroups according to the cDDD quartiles. Survival was analyzed using Kaplan-Meier and Cox regression analysis...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27806289/vulnerability-of-purkinje-cells-generated-from-spinocerebellar-ataxia-type-6-patient-derived-ipscs
#15
Yoshihito Ishida, Hideshi Kawakami, Hiroyuki Kitajima, Ayaka Nishiyama, Yoshiki Sasai, Haruhisa Inoue, Keiko Muguruma
Spinocerebellar ataxia type 6 (SCA6) is a dominantly inherited neurodegenerative disease characterized by loss of Purkinje cells in the cerebellum. SCA6 is caused by CAG trinucleotide repeat expansion in CACNA1A, which encodes Cav2.1, α1A subunit of P/Q-type calcium channel. However, the pathogenic mechanism and effective therapeutic treatments are still unknown. Here, we have succeeded in generating differentiated Purkinje cells that carry patient genes by combining disease-specific iPSCs and self-organizing culture technologies...
November 1, 2016: Cell Reports
https://www.readbyqxmd.com/read/27778156/factors-predicting-survival-in-als-a-multicenter-italian-study
#16
Andrea Calvo, Cristina Moglia, Christian Lunetta, Kalliopi Marinou, Nicola Ticozzi, Gianluca Drago Ferrante, Carlo Scialo, Gianni Sorarù, Francesca Trojsi, Amelia Conte, Yuri M Falzone, Rosanna Tortelli, Massimo Russo, Adriano Chiò, Valeria Ada Sansone, Gabriele Mora, Vincenzo Silani, Paolo Volanti, Claudia Caponnetto, Giorgia Querin, Maria Rosaria Monsurrò, Mario Sabatelli, Nilo Riva, Giancarlo Logroscino, Sonia Messina, Nicola Fini, Jessica Mandrioli
The aim of this multicenter, retrospective study is to investigate the role of clinical characteristics and therapeutic intervention on ALS prognosis. The study included patients diagnosed from January 1, 2009 to December 31, 2013 in 13 Italian referral centers for ALS located in 10 Italian regions. Caring neurologists collected a detailed phenotypic profile and follow-up data until death into an electronic database. One center collected also data from a population-based registry for ALS. 2648 incident cases were collected...
October 24, 2016: Journal of Neurology
https://www.readbyqxmd.com/read/27776762/soluble-n-ethylmaleimide-sensitive-factor-attachment-receptor-snare-protein-involved-in-the-remission-of-depression-by-acupuncture-in-rats
#17
Ling Fan, Zhao Chen, Wenbin Fu, Nenggui Xu, Jianhua Liu, Aiping Lu, Ziping Li, Shengyong Su, Taixiang Wu, Aihua Ou
This study aims to investigate the molecular mechanisms of acupuncture in the remission of depression. A depressive disorder model was induced by exposing Sprague-Dawley rats to chronic unpredictable stress. The rats were divided into five groups: healthy (blank group) and stressed rats (model group), and stressed rats treated with acupuncture (acupuncture group), riluzole (riluzole group), acupuncture combined with botulinum toxin A (BTX-A) injection (acupuncture+BTX-A group) or riluzole combined with BTX-A injection (riluzole+BTX-A group)...
October 2016: Journal of Acupuncture and Meridian Studies
https://www.readbyqxmd.com/read/27710012/mechanistic-studies-of-capsaicin-induced-apnea-in-rodents
#18
Jun Ren, Xiuqing Ding, John J Greer
Inhalation of capsaicin based sprays can cause central respiratory depression and lethal apneas. There are contradictory reports regarding the sites of capsaicin action. Further, an understanding of the neurochemical mechanisms underlying capsaicin-induced apneas and the development of pharmacological interventions are lacking. The main objectives were to perform a systematic study of the mechanisms of action of capsaicin-induced apneas and to provide insights relevant to pharmacological intervention. In vitro and in vivo rat and TRPV1-null mouse models were used to measure respiratory parameters and seizure-like activity in the presence of capsaicin and compounds that modulate glutamatergic neurotransmission...
October 6, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27701153/electrospun-fibers-for-drug-delivery-after-spinal-cord-injury-and-the-effects-of-drug-incorporation-on-fiber-properties
#19
Christopher D L Johnson, Anthony R D'Amato, Ryan J Gilbert
There is currently no cure for individuals with spinal cord injury (SCI). While many promising approaches are being tested in clinical trials, the complexity of SCI limits several of these approaches from aiding complete functional recovery. Several different categories of biomaterials are investigated for their ability to guide axonal regeneration, to deliver proteins or small molecules locally, or to improve the viability of transplanted stem cells. The purpose of this study is to provide a brief overview of SCI, present the different categories of biomaterial scaffolds that direct and guide axonal regeneration, and then focus specifically on electrospun fiber guidance scaffolds...
2016: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/27694488/identification-and-outcomes-of-clinical-phenotypes-in-amyotrophic-lateral-sclerosis-motor-neuron-disease-australian-national-motor-neuron-disease-observational-cohort
#20
Paul Talman, Thi Duong, Steve Vucic, Susan Mathers, Svetha Venkatesh, Robert Henderson, Dominic Rowe, David Schultz, Robert Edis, Merrilee Needham, Richard Macdonnell, Pamela McCombe, Carol Birks, Matthew Kiernan
OBJECTIVE: To capture the clinical patterns, timing of key milestones and survival of patients presenting with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) within Australia. METHODS: Data were prospectively collected and were timed to normal clinical assessments. An initial registration clinical report form (CRF) and subsequent ongoing assessment CRFs were submitted with a completion CRF at the time of death. DESIGN: Prospective observational cohort study...
September 30, 2016: BMJ Open
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