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https://www.readbyqxmd.com/read/28644824/mechanism-underlying-acupuncture-ameliorated-depressive-behaviors-by-enhancing-glial-glutamate-transporter-in-chronic-unpredictable-mild-stress-cums-rats
#1
Ding Luo, Rui Ma, Yanan Wu, Xuechun Zhang, Yue Liu, Lin Wang, Wenbin Fu
BACKGROUND Major depressive disorder (MDD) is a recurrent mental illness worldwide. The glutamatergic neurotransmission system is now a target for antidepressant therapy because it takes part in synaptic plasticity and cognition in physical condition and has a potential excitatory neurotoxicity in pathological conditions. Glial glutamate transporter EAAT2 performs 90% of Glu neurotransmission. Therefore, the aim of the study was to evaluate the effect of acupuncture on depressive behaviors and EAAT2 in CUMS...
June 23, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28630169/patient-specific-drug-screening-using-a-human-induced-pluripotent-stem-cell-model-of-catecholaminergic-polymorphic-ventricular-tachycardia-type-2
#2
Leonid Maizels, Irit Huber, Gil Arbel, Anke J Tijsen, Amira Gepstein, Asaad Khoury, Lior Gepstein
BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia type 2 (CPVT2) results from autosomal recessive CASQ2 mutations, causing abnormal Ca(2+)-handling and malignant ventricular arrhythmias. We aimed to establish a patient-specific human induced pluripotent stem cell (hiPSC) model of CPVT2 and to use the generated hiPSC-derived cardiomyocytes to gain insights into patient-specific disease mechanism and pharmacotherapy. METHODS AND RESULTS: hiPSC cardiomyocytes were derived from a CPVT2 patient (D307H-CASQ2 mutation) and from healthy controls...
June 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28623867/a-validated-uhplc-ms-ms-method-for-the-measurement-of-riluzole-in-plasma-and-myocardial-tissue-samples
#3
Suzanne L Parker, Yarmarly C Guerra Valero, Jeffrey Lipman, Steven Weiss, Camilla Smith, Lyndal Russell, Paul Smith, Jason A Roberts, Steven C Wallis
Through blocking the cardiac persistent sodium current, riluzole has the potential to prevent myocardial damage post cardiac bypass surgery. A sensitive UHPLC-MS/MS method was developed and validated for quantitation of riluzole and 5-methoxypsoralen in human plasma and myocardial tissue homogenate using a liquid-liquid extraction with dichloromethane. The chromatographic separation was achieved using Shimadzu Shim-pack XR-ODS III, 2.0 x 50 mm, 1.6 μm column with a gradient mobile phase comprising of methanol and ammonium acetate buffer pH 3...
June 17, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28616022/therapeutic-opportunities-and-challenges-of-induced-pluripotent-stem-cells-derived-motor-neurons-for-treatment-of-amyotrophic-lateral-sclerosis-and-motor-neuron-disease
#4
REVIEW
Manoj Kumar Jaiswal
Amyotrophic lateral sclerosis (ALS) and motor neuron diseases (MNDs) are progressive neurodegenerative diseases that affect nerve cells in the brain affecting upper and lower motor neurons (UMNs/LMNs), brain stem and spinal cord. The clinical phenotype is characterized by loss of motor neurons (MNs), muscular weakness and atrophy eventually leading to paralysis and death due to respiratory failure within 3-5 years after disease onset. No effective treatment or cure is currently available that halts or reverses ALS and MND except FDA approved drug riluzole that only modestly slows the progression of ALS in some patients...
May 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28593575/the-role-of-herg1-ion-channels-in-epithelial-mesenchymal-transition-and-the-capacity-of-riluzole-to-reduce-cisplatin-resistance-in-colorectal-cancer-cells
#5
Angelo Fortunato
PURPOSE: The transition of cells from the epithelial to the mesenchymal state (EMT) plays an important role in tumor progression. EMT allows cells to acquire mobility, stem-like behavior and resistance to apoptosis and drug treatment. These features turn EMT into a central process in tumor biology. Ion channels are attractive targets for the treatment of cancer since they play critical roles in controlling a wide range of physiological processes that are frequently deregulated in cancer...
June 7, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28591718/riluzole-exerts-distinct-antitumor-effects-from-a-metabotropic-glutamate-receptor-1-specific-inhibitor-on-breast-cancer-cells
#6
Sonia C Dolfi, Daniel J Medina, Aparna Kareddula, Bhavna Paratala, Ashley Rose, Jatinder Dhami, Suzie Chen, Shridar Ganesan, Gillian Mackay, Alexei Vazquez, Kim M Hirshfield
Recent evidence suggests that glutamate signaling plays an important role in cancer. Riluzole is a glutamate release inhibitor and FDA-approved drug for the treatment of amyotrophic lateral sclerosis. It has been investigated as an inhibitor of cancer cell growth and tumorigenesis with the intention of repurposing it for the treatment of cancer. Riluzole is thought to act by indirectly inhibiting glutamate signaling. However, the specific effects of riluzole in breast cancer cells are not well understood. In this study, the anti-cancer effects of riluzole were explored in a panel of breast cancer cell lines in comparison to the metabotropic glutamate receptor 1-specific inhibitor BAY 36-7620...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28586761/riluzole-a-potential-therapeutic-intervention-in-human-brain-tumor-stem-like-cells
#7
Swetlana Sperling, Thiha Aung, Sabine Martin, Veit Rohde, Milena Ninkovic
A small subpopulation of tumor stem-like cells has the capacity to initiate tumors and mediate radio- and chemoresistance in diverse cancers hence also in glioblastoma (GBM). It has been reported that this capacity of tumor initiation in the brain is mainly dependent on the body's nutrient supply. This population of so-called brain tumor initiating or brain tumor stem-like cells (BTSCs) is able to extract nutrients like glucose with a higher affinity. Riluzole, a drug approved for treating amyotrophic lateral sclerosis (ALS), was reported to possess anticancer properties, affecting the glutamate metabolism...
May 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28571527/assessment-and-management-of-acute-spinal-cord-injury-from-point-of-injury-to-rehabilitation
#8
Laureen D Hachem, Christopher S Ahuja, Michael G Fehlings
CONTEXT: Spinal cord injury (SCI) is a devastating condition that can lead to significant neurological impairment and reduced quality of life. Despite advancements in our understanding of the pathophysiology and secondary injury mechanisms involved in SCI, there are currently very few effective treatments for this condition. The field, however, is rapidly changing as new treatments are developed and key discoveries are made. METHODS: In this review, we outline the pathophysiology, management, and long-term rehabilitation of individuals with traumatic SCI...
June 1, 2017: Journal of Spinal Cord Medicine
https://www.readbyqxmd.com/read/28553836/a-randomized-double-blind-placebo-controlled-sequential-parallel-comparison-design-trial-of-adjunctive-riluzole-for-treatment-resistant-major-depressive-disorder
#9
Sanjay J Mathew, Ralitza Gueorguieva, Cynthia Brandt, Maurizio Fava, Gerard Sanacora
Riluzole is a glutamate-modulating agent with neuroprotective properties approved for use in amyotrophic lateral sclerosis. The efficacy and safety of riluzole vs placebo as an adjunct to antidepressant medication in outpatients with major depressive disorder (MDD) was examined in a 3-site, 8-week, randomized, double-blind, placebo-controlled, fixed-dose trial using a sequential parallel comparison design comprised of two phases of 4 weeks. Patients with MDD in a current major depressive episode (N=104) with an inadequate response to either a prospective or a historical trial of an antidepressant medication were randomized in a 2 : 3 : 3 ratio to the treatment sequences of riluzole/riluzole, placebo/placebo, and placebo/riluzole, respectively...
May 29, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28540118/spinal-cord-injury-in-the-geriatric-population-risk-factors-treatment-options-and-long-term-management
#10
REVIEW
Tochukwu C Ikpeze, Addisu Mesfin
Spinal cord injuries (SCIs) are sustained by more than 12 500 patients per year in the United States and more globally. The SCIs disproportionately affect the elderly, especially men. Approximately 60% of these injuries are sustained traumatically through falls, but nontraumatic causes including infections, tumors, and medication-related epidural bleeding have also been documented. Preexisting conditions such as ankylosing spondylitis and diffuse idiopathic skeletal hyperostosis can render the spine stiff and are risk factors as well as cervical spondylosis and ensuing cervical stenosis...
June 2017: Geriatric Orthopaedic Surgery & Rehabilitation
https://www.readbyqxmd.com/read/28534874/shifting-brain-inhibitory-balance-and-connectivity-of-the-prefrontal-cortex-of-adults-with-autism-spectrum-disorder
#11
L A Ajram, J Horder, M A Mendez, A Galanopoulos, L P Brennan, R H Wichers, D M Robertson, C M Murphy, J Zinkstok, G Ivin, M Heasman, D Meek, M D Tricklebank, G J Barker, D J Lythgoe, R A E Edden, S C Williams, D G M Murphy, G M McAlonan
Currently, there are no effective pharmacologic treatments for the core symptoms of autism spectrum disorder (ASD). There is, nevertheless, potential for progress. For example, recent evidence suggests that the excitatory (E) glutamate and inhibitory (I) GABA systems may be altered in ASD. However, no prior studies of ASD have examined the 'responsivity' of the E-I system to pharmacologic challenge; or whether E-I modulation alters abnormalities in functional connectivity of brain regions implicated in the disorder...
May 23, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28525376/exploiting-ros-and-metabolic-differences-to-kill-cisplatin-resistant-lung-cancer
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
Wojciech Zmysłowski, Anna M Cabaj, Urszula Sławińska
[This corrects the article DOI: 10.1371/journal.pone.0170235.].
2017: PloS One
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