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https://www.readbyqxmd.com/read/28525376/exploiting-ros-and-metabolic-differences-to-kill-cisplatin-resistant-lung-cancer
#1
Medhi Wangpaichitr, Chunjing Wu, Ying Ying Li, Dan J M Nguyen, Hande Kandemir, Sumedh Shah, Shumei Chen, Lynn G Feun, Jeffrey S Prince, Macus T Kuo, Niramol Savaraj
Cisplatin resistance remains a major problem in the treatment of lung cancer. We have discovered that cisplatin resistant (CR) lung cancer cells, regardless of the signaling pathway status, share the common parameter which is an increase in reactive oxygen species (ROS) and undergo metabolic reprogramming. CR cells were no longer addicted to the glycolytic pathway, but rather relied on oxidative metabolism. They took up twice as much glutamine and were highly sensitive to glutamine deprivation. Glutamine is hydrolyzed to glutamate for glutathione synthesis, an essential factor to abrogate high ROS via xCT antiporter...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524214/-possible-treatments-for-infantile-spinal-atrophy
#2
S I Pascual-Pascual, M Garcia-Romero
The new treatments of spinal muscular atrophy (SMA) due by SMN1 gene deletions are reviewed. There are several ways to increase the protein SMN, its activity and persistence in the tissues. Neuroprotective drugs as olesoxime or riluzole, and drugs acting by epigenetic mechanisms, as histone deacetylase inhibitors, have shown positive effects in preclinical studies but no clear efficacy in clinical trials. They might give in the future added benefits when used associated to other genetic modifying drugs. The best improvements in murine models of SMA and in clinical trials have been reached with antisense oligonucleotides, drugs that modify the splicing of SMN2, and they are expected to get better in the near future...
May 17, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/28490573/dok7-gene-therapy-enhances-motor-activity-and-life-span-in-als-model-mice
#3
Sadanori Miyoshi, Tohru Tezuka, Sumimasa Arimura, Taro Tomono, Takashi Okada, Yuji Yamanashi
Amyotrophic lateral sclerosis (ALS) is a progressive, multifactorial motor neurodegenerative disease with severe muscle atrophy. The glutamate release inhibitor riluzole is the only medication approved by the FDA, and prolongs patient life span by a few months, testifying to a strong need for new treatment strategies. In ALS, motor neuron degeneration first becomes evident at the motor nerve terminals in neuromuscular junctions (NMJs), the cholinergic synapse between motor neuron and skeletal muscle; degeneration then progresses proximally, implicating the NMJ as a therapeutic target...
May 10, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28485008/l-carnosine-as-an-adjuvant-to-fluvoxamine-in-treatment-of-obsessive-compulsive-disorder-a-randomized-double-blind-study
#4
Somaye Arabzadeh, Maryam Shahhossenie, Bita Mesgarpour, Farzin Rezaei, Mohammad Reza Shalbafan, Zahra Ghiasi, Shahin Akhondzadeh
BACKGROUND: Dysregulation of glutamate is implicated in the pathogenesis of obsessive-compulsive disorder (OCD). Consistently, glutamate-modulating agents, such as riluzole and memantine have been used in OCD treatment. Previous research has identified some neuroprotective role for L-carnosine potentially via its modulatory effect on glutamate. Here, we assessed the efficacy of L-carnosine as adjuvant to fluvoxamine in OCD treatment. METHODS: Forty-four patients diagnosed with moderate to severe OCD were recruited in a randomized double-blind trial...
May 8, 2017: Human Psychopharmacology
https://www.readbyqxmd.com/read/28462043/lack-of-riluzole-efficacy-in-the-progression-of-the-neurodegenerative-phenotype-in-a-new-conditional-mouse-model-of-striatal-degeneration
#5
Grzegorz Kreiner, Katarzyna Rafa-Zabłocka, Piotr Chmielarz, Monika Bagińska, Irena Nalepa
BACKGROUND: Huntington's disease (HD) is a rare familial autosomal dominant neurodegenerative disorder characterized by progressive degeneration of medium spiny neurons (MSNs) located in the striatum. Currently available treatments of HD are only limited to alleviating symptoms; therefore, high expectations for an effective therapy are associated with potential replacement of lost neurons through stimulation of postnatal neurogenesis. One of the drugs of potential interest for the treatment of HD is riluzole, which may act as a positive modulator of adult neurogenesis, promoting replacement of damaged MSNs...
2017: PeerJ
https://www.readbyqxmd.com/read/28455267/metabotropic-glutamate-receptor-5-mediates-the-suppressive-effect-of-6-ohda-induced-model-of-parkinson-s-disease-on-liver-cancer
#6
Shao-Song Xi, Xiao-Xu Bai, Li Gu, Li-Hui Bao, Hui-Min Yang, Wei An, Xiao-Min Wang, Hong Zhang
Numerous epidemiological studies suggested that there is a variable cancer risk in patients with Parkinson's disease (PD). However, the underlying mechanisms remain unclear. In the present study, the role of metabotropic glutamate receptor 5 (mGluR5) has been investigated in 6-hydroxydopamine (6-OHDA)-induced PD combined with liver cancer both in vitro and in vivo. We found that PD cellular model from 6-OHDA-lesioned MN9D cells suppressed the growth, migration, and invasion of Hepa1-6 cells via down-regulation of mGluR5-mediated ERK and Akt pathway...
April 26, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28446951/power-spectral-density-analysis-of-purkinje-cell-tonic-and-burst-firing-patterns-from-a-rat-model-of-ataxia-and-riluzole-treated
#7
Samira Abbasi, Ataollah Abbasi, Yashar Sarbaz, Mahyar Janahmadi
INTRODUCTION: Purkinje Cell (PC) output displays a complex firing pattern consisting of high frequency sodium spikes and low frequency calcium spikes, and disruption in this firing behavior may contribute to cerebellar ataxia. Riluzole, neuroprotective agent, has been demonstrated to have neuroprotective effects in cerebellar ataxia. Here, the spectral analysis of PCs firing in control, 3-acetylpyridine (3-AP), neurotoxin agent, treated alone and riluzole plus 3-AP treated were investigated to determine changes in the firing properties...
January 2017: Basic and Clinical Neuroscience
https://www.readbyqxmd.com/read/28446118/motor-neurone-disease-progress-and-challenges
#8
REVIEW
Thanuja Dharmadasa, Robert D Henderson, Paul S Talman, Richard Al Macdonell, Susan Mathers, David W Schultz, Merrillee Needham, Margaret Zoing, Steve Vucic, Matthew C Kiernan
Major progress has been made over the past decade in the understanding of motor neurone disease (MND), changing the landscape of this complex disease. Through identifying positive prognostic factors, new evidence-based standards of care have been established that improve patient survival, reduce burden of disease for patients and their carers, and enhance quality of life. These factors include early management of respiratory dysfunction with non-invasive ventilation, maintenance of weight and nutritional status, as well as instigation of a multidisciplinary team including neurologists, general practitioners and allied health professionals...
May 1, 2017: Medical Journal of Australia
https://www.readbyqxmd.com/read/28426787/correction-treatment-with-riluzole-restores-normal-control-of-soleus-and-extensor-digitorum-longus-muscles-during-locomotion-in-adult-rats-after-sciatic-nerve-crush-at-birth
#9
Wojciech Zmysłowski, Anna M Cabaj, Urszula Sławińska
[This corrects the article DOI: 10.1371/journal.pone.0170235.].
2017: PloS One
https://www.readbyqxmd.com/read/28423185/functional-identification-of-activity-regulated-high-affinity-glutamine-transport-in-hippocampal-neurons-inhibited-by-riluzole
#10
Jeffrey D Erickson
Glutamine (Gln) is considered the preferred precursor for the neurotransmitter pool of glutamate (Glu), the major excitatory transmitter in the mammalian CNS. Here, an activity-regulated, high-affinity Gln transport system is described in developing and mature neuron-enriched hippocampal cultures that is potently inhibited by riluzole (IC50 1.3 +/- 0.5μM), an anti-glutamatergic drug, and is blocked by low concentrations of 2-(methylamino)isobutyrate (MeAIB), a system A transport inhibitor. K(+) -stimulated MeAIB transport displays an affinity (Km ) for MeAIB of 37 +/- 1...
April 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28406335/clinical-efficacy-of-edaravone-for-the-treatment-of-amyotrophic-lateral-sclerosis
#11
Hideyuki Sawada
Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disease. Although the pathogenesis remains unresolved, oxidative stress is known to play a pivotal role. Edaravone works in the central nervous system as a potent scavenger of oxygen radicals. In ALS mouse models, edaravone suppresses motor functional decline and nitration of tyrosine residues in the cerebrospinal fluid. Areas covered: Three clinical trials, one phase II open-label trial, and two phase III placebo-control randomized trials were reviewed...
May 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28400790/current-view-and-perspectives-in-amyotrophic-lateral-sclerosis
#12
REVIEW
Stéphane Mathis, Philippe Couratier, Adrien Julian, Philippe Corcia, Gwendal Le Masson
Amyotrophic lateral sclerosis (ALS), identified as a distinct clinical entity by Charcot since the end of the nineteenth century, is a devastating and fatal neurodegenerative disorder that affects motor neurons in the brain, brainstem and spinal cord. Survival of patients with ALS is associated with several factors such as clinical phenotype, age at onset, gender, early presence of respiratory failure, weight loss and treatment with Riluzole (the only disease-modifying drug approved for this disease). Nowadays, there is still no curative treatment for ALS: palliative care and symptomatic treatment are therefore essential components in the management of these patients...
February 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28387141/nationwide-incidence-of-motor-neuron-disease-using-the-french-health-insurance-information-system-database
#13
Sofiane Kab, Frédéric Moisan, Pierre-Marie Preux, Benoît Marin, Alexis Elbaz
OBJECTIVE: There are no estimates of the nationwide incidence of motor neuron disease (MND) in France. We used the French health insurance information system to identify incident MND cases (2012-2014), and compared incidence figures to those from three external sources. METHODS: We identified incident MND cases (2012-2014) based on three data sources (riluzole claims, hospitalisation records, long-term chronic disease benefits), and computed MND incidence by age, gender, and geographic region...
April 7, 2017: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/28384832/obsessive-compulsive-disorder-advances-in-diagnosis-and-treatment
#14
Matthew E Hirschtritt, Michael H Bloch, Carol A Mathews
Importance: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder associated with significant impairment and a lifetime prevalence of 1% to 3%; however, it is often missed in primary care settings and frequently undertreated. Objective: To review the most current data regarding screening, diagnosis, and treatment options for OCD. Evidence Review: We searched PubMed, EMBASE, and PsycINFO to identify randomized controlled trials (RCTs), meta-analyses, and systematic reviews that addressed screening and diagnostic and treatment approaches for OCD among adults (≥18 years), published between January 1, 2011, and September 30, 2016...
April 4, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28382000/als-clinical-trials-review-20-years-of-failure-are-we-any-closer-to-registering-a-new-treatment
#15
REVIEW
Dmitry Petrov, Colin Mansfield, Alain Moussy, Olivier Hermine
Amyotrophic lateral sclerosis (ALS) is a devastating condition with an estimated mortality of 30,000 patients a year worldwide. The median reported survival time since onset ranges from 24 to 48 months. Riluzole is the only currently approved mildly efficacious treatment. Riluzole received marketing authorization in 1995 in the USA and in 1996 in Europe. In the years that followed, over 60 molecules have been investigated as a possible treatment for ALS. Despite significant research efforts, the overwhelming majority of human clinical trials (CTs) have failed to demonstrate clinical efficacy...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28377742/dysphagia-in-amyotrophic-lateral-sclerosis-impact-on-patient-behavior-diet-adaptation-and-riluzole-management
#16
Emanuela Onesti, Ilenia Schettino, Maria Cristina Gori, Vittorio Frasca, Marco Ceccanti, Chiara Cambieri, Giovanni Ruoppolo, Maurizio Inghilleri
This retrospective study aimed to investigate the clinical features associated with deteriorated swallow in amyotrophic lateral sclerosis (ALS) patients with spinal and bulbar onset, describe the modification of diet and liquid intake, and assess the impact of dysphagia on the use of riluzole. One hundred forty-five patients were observed periodically every 3-6 months. They underwent routinely fiberoptic endoscopic evaluation of swallowing (FEES) and spirometry; dysphagia severity was classified according to the Penetration Aspiration Scale and the Pooling score (P-score) integrated with other parameters such as sensation, collaboration, and age (P-SCA score)...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28359884/administration-of-riluzole-into-the-basolateral-amygdala-has-an-anxiolytic-like-effect-and-enhances-recognition-memory-in-the-rat
#17
Azusa Sugiyama, Akiyoshi Saitoh, Misa Yamada, Jun-Ichiro Oka, Mitsuhiko Yamada
It is widely thought that inactivation of the glutamatergic system impairs recognition memory in rodents. However, we previously demonstrated that systemic administration of riluzole, which blocks the glutamatergic system, enhances recognition memory in the rat novel object recognition (NOR) test. The mechanisms underlying this paradoxical effect of riluzole on recognition memory remain unclear. In the present study, adult male Wistar rats were bilaterally cannulated in the basolateral amygdala (BLA) to examine the effects of intra-BLA administration of riluzole...
June 1, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28350947/traumatic-spinal-cord-injury-repair-and-regeneration
#18
Christopher S Ahuja, Satoshi Nori, Lindsay Tetreault, Jefferson Wilson, Brian Kwon, James Harrop, David Choi, Michael G Fehlings
BACKGROUND: Traumatic spinal cord injuries (SCI) have devastating consequences for the physical, financial, and psychosocial well-being of patients and their caregivers. Expediently delivering interventions during the early postinjury period can have a tremendous impact on long-term functional recovery. PATHOPHYSIOLOGY: This is largely due to the unique pathophysiology of SCI where the initial traumatic insult (primary injury) is followed by a progressive secondary injury cascade characterized by ischemia, proapoptotic signaling, and peripheral inflammatory cell infiltration...
March 1, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28338546/a-double-blind-placebo-controlled-pilot-study-of-riluzole-monotherapy-for-acute-bipolar-depression
#19
Lawrence T Park, Marc S Lener, Matthew Hopkins, Nicolas Iadorola, Rodrigo Machado-Vieira, Elizabeth Ballard, Allison Nugent, Carlos A Zarate
BACKGROUND: Glutamatergic system abnormalities are implicated in the pathophysiology and treatment of both major depressive disorder and bipolar depression (BDep). Subsequent to studies demonstrating the rapid and robust antidepressant effects of ketamine, an N-methyl-D-aspartate receptor antagonist, other glutamatergic modulators are now being studied in clinical trials of mood disorders. A previous open-label study found that riluzole, administered in combination with the mood stabilizer lithium, had antidepressant effects...
June 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28331009/the-modulation-of-two-motor-behaviours-by-persistent-sodium-currents-in-xenopus-laevis-tadpoles
#20
Erik Svensson, Hugo Jeffreys, Wen-Chang Li
Persistent sodium currents (INaP) are common in neuronal circuitries and they have been implicated in several diseases like amyotrophic lateral sclerosis (ALS) and epilepsy. However, the role of INaP in the regulation of specific behaviours is still poorly understood. Here we have characterized INaP and investigated its role in the swimming and struggling behaviour of Xenopus tadpoles. INaP was identified in three groups of neurons, namely sensory Rohon-Beard neurons (RB neurons), descending interneurons (dINs), and non-dINs (neurons rhythmically active in swimming)...
March 22, 2017: Journal of Neurophysiology
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