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https://www.readbyqxmd.com/read/28229367/inhibition-of-mtor-pathway-by-rapamycin-decreases-p-glycoprotein-expression-and-spontaneous-seizures-in-pharmacoresistant-epilepsy
#1
Xiaosa Chi, Cheng Huang, Rui Li, Wei Wang, Mengqian Wu, Jinmei Li, Dong Zhou
The mammalian target of rapamycin (mTOR) has been demonstrated to mediate multidrug resistance in various tumors by inducing P-glycoprotein (P-gp) overexpression. Here, we investigated the correlation between the mTOR pathway and P-gp expression in pharmacoresistant epilepsy. Temporal cortex specimens were obtained from patients with refractory mesial temporal lobe epilepsy (mTLE) and age-matched controls who underwent surgeries at West China Hospital of Sichuan University between June 2014 and May 2015. We established a rat model of epilepsy kindled by coriaria lactone (CL) and screened pharmacoresistant rats (non-responders) using phenytoin...
February 22, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28217049/effectiveness-of-sodium-thiopentone-propofol-and-etomidate-as-an-ideal-intravenous-anesthetic-agent-for-modified-electroconvulsive-therapy
#2
Altaf Hussain Mir, Nida Farooq Shah, Mehraj Ud Din, Shabir Ahmad Langoo, Fayaz Ahmad Reshi
INTRODUCTION: Electroconvulsive therapy (ECT) is a well-established psychiatric treatment in which seizures are electrically induced in patients for therapeutic effects. ECT can produce severe disturbances in the cardiovascular system and a marked increase in cerebral blood flow and intracranial pressure. These cardiovascular changes may be altered using various anesthetic drugs. AIM AND OBJECTIVES: This study was undertaken to compare the effects of intravenous (IV) sodium thiopentone, propofol, and etomidate, used as IV anesthetic agents in modified ECT as regards, induction time and quality of anesthesia, alteration of hemodynamics, seizure duration, and recovery time...
January 2017: Saudi Journal of Anaesthesia
https://www.readbyqxmd.com/read/28215696/recurrent-venous-thrombosis-under-rivaroxaban-and-carbamazepine-for-symptomatic-epilepsy
#3
Claudia Stöllberger, Josef Finsterer
BACKGROUND: The direct oral anticoagulant (DOAC) rivaroxaban, an oral Factor Xa inhibitor, is increasingly used as an alternative to vitamin-K-antagonists (VKAs). Absorption and elimination of DOACs are dependent on the permeability glycoprotein (P-gp) efflux transporter protein system, and DOACs are substrates of the hepatic cytochrome P 450 3A4 (CYP3A4) enzymes. Therefore, drug-interactions may occur when DOACs are administered with drugs affecting the activity of P-gp or CYP3A4 systems...
February 3, 2017: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/28215473/machine-learning-based-prediction-of-adverse-drug-effects-an-example-of-seizure-inducing-compounds
#4
Mengxuan Gao, Hideyoshi Igata, Aoi Takeuchi, Kaoru Sato, Yuji Ikegaya
Various biological factors have been implicated in convulsive seizures, involving side effects of drugs. For the preclinical safety assessment of drug development, it is difficult to predict seizure-inducing side effects. Here, we introduced a machine learning-based in vitro system designed to detect seizure-inducing side effects. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices, while 14 drugs were bath-perfused at 5 different concentrations each. For each experimental condition, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning...
January 28, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28212985/nonsteroidal-anti-inflammatory-drugs-in-clinical-and-experimental-epilepsy
#5
REVIEW
Beatrice Mihaela Radu, Florin Bogdan Epureanu, Mihai Radu, Paolo Francesco Fabene, Giuseppe Bertini
Current antiepileptic drugs have limited efficacy and provide little or no benefits in 30% of the patients. Given that a role for brain inflammation in epilepsy has been repeatedly reported in recent years, the potential of anti-inflammatory drugs should be explored in depth, as they may provide new therapeutical approaches in preventing or reducing epileptogenesis. Here, we review preclinical (both in vivo and in vitro) and clinical epilepsy studies in which nonsteroidal antiinflammatory drugs (NSAIDs), i...
February 9, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28209738/optogenetic-low-frequency-stimulation-of-specific-neuronal-populations-abates-ictogenesis
#6
Zahra Shiri, Maxime Lévesque, Guillaume Etter, Frédéric Manseau, Sylvain Williams, Massimo Avoli
Despite many advances made in understanding the pathophysiology of epileptic disorders, seizures remain poorly controlled in approximately one third of mesial temporal lobe epilepsy patients. Here, we established the efficacy of cell type-specific low-frequency stimulation (LFS) in controlling ictogenesis in the mouse entorhinal cortex (EC) in an in vitro brain slice preparation. Specifically, we used 1 Hz optogenetic stimulation of Ca(2+)/calmodulin-dependent protein kinase II-positive principal cells as well as of parvalbumin- or somatostatin-positive interneurons to study the effects of such repetitive activation on epileptiform discharges induced by 4-aminopyridine...
February 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28195743/p-gp-protein-expression-and-transport-activity-in-rodent-seizure-models-and-human-epilepsy
#7
Anika M S Hartz, Anton Pekcec, Emma L B Soldner, Yu Zhong, Juli Schlichtiger, Bjoern Bauer
A cure for epilepsy is currently not available, and seizure genesis, seizure recurrence, and resistance to anti-seizure drugs remain serious clinical problems. Studies show that the blood-brain barrier is altered in animal models of epilepsy and in epileptic patients. In this regard, seizures increase expression of blood-brain barrier efflux transporters such as P-glycoprotein (P-gp), which is thought to reduce brain uptake of anti-seizure drugs, and thus, contribute to anti-seizure drug resistance. The goal of the current study was to assess the viability of combining in vivo and ex vivo preparations of isolated brain capillaries from animal models of seizures and epilepsy as well as from patients with epilepsy to study P-gp at the blood-brain barrier...
February 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28188357/analgesic-antiallodynic-and-anticonvulsant-activity-of-novel-hybrid-molecules-derived-from-n-benzyl-2-2-5-dioxopyrrolidin-1-yl-propanamide-and-2-2-5-dioxopyrrolidin-1-yl-butanamide-in-animal-models-of-pain-and-epilepsy
#8
Anna Rapacz, Krzysztof Kamiński, Jolanta Obniska, Paulina Koczurkiewicz, Elżbieta Pękala, Barbara Filipek
The purpose of the present study was to examine the analgesic activity of six novel hybrid molecules, which demonstrated in the previous research anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole seizure (scPTZ) tests in mice. The antinociceptive properties were estimated in three models of pain in mice-the hot plate test, the formalin test, and in the oxaliplatin-induced neuropathy. Moreover, extended anticonvulsant studies were carried out and the antiseizure activity was investigated in the 6-Hz test...
February 10, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28181916/4-phenylbutyric-acid-and-metformin-decrease-sensitivity-to-pentylenetetrazol-induced-seizures-in-a-malin-knockout-model-of-lafora-disease
#9
Gentzane Sánchez-Elexpuru, José M Serratosa, Pascual Sanz, Marina P Sánchez
Lafora disease (LD) is a rare adolescent-onset progressive myoclonic epilepsy caused by loss-of-function mutations either in the EPM2A gene encoding laforin or in the EPM2B gene encoding malin. Mouse models with deletion in the Epm2a or the Epm2b gene show intracellular aggregates of polyglucosans (Lafora bodies) and neurological complications that resemble those observed in patients with LD. In the absence of laforin or malin expression, mice also show different degrees of hyperexcitability, as reflected by an enhanced response to the convulsant drug pentylenetetrazol (PTZ)...
February 8, 2017: Neuroreport
https://www.readbyqxmd.com/read/28181126/anti-angiogenic-tyrosine-kinase-inhibitors-and-reversible-posterior-leukoencephalopathy-syndrome-could-hypomagnesaemia-be-the-trigger
#10
REVIEW
Rashmi R Shah
Reversible posterior leukoencephalopathy syndrome (RPLS), also known frequently as posterior reversible encephalopathy syndrome (PRES), is a characteristic acute neuro-radiology syndrome with clinical presentation that typically includes acute hypertension, seizures and other neurological symptoms and signs. Many patients with RPLS have (a history of) pre-existing hypertension and in receipt of diuretics. It is being diagnosed more frequently and in association with an increasing number of morbidities and medications...
February 9, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28167116/therapeutic-potential-of-an-anti-high-mobility-group-box-1-monoclonal-antibody-in-epilepsy
#11
Junli Zhao, Yi Wang, Cenglin Xu, Keyue Liu, Ying Wang, Liying Chen, Xiaohua Wu, Feng Gao, Yi Guo, Junming Zhu, Shuang Wang, Masahiro Nishibori, Zhong Chen
Brain inflammation is a major factor in epilepsy, and the high mobility group box-1 (HMGB1) protein is known to contribute significantly to the generation of seizures. Here, we investigated the therapeutic potential of an anti-HMGB1 monoclonal antibody (mAb) in epilepsy. anti-HMGB1 mAb attenuated both acute seizure models (maximal electroshock seizure, pentylenetetrazole-induced and kindling-induced), and chronic epilepsy model (kainic acid-induced) in a dose-dependent manner. Meanwhile, the anti-HMGB1 mAb also attenuated seizure activities of human brain slices obtained from surgical resection from drug-resistant epilepsy patients...
February 3, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28166388/toll-like-receptor-3-deficiency-decreases-epileptogenesis-in-a-pilocarpine-model-of-se-induced-epilepsy-in-mice
#12
Adi Gross, Felix Benninger, Ravit Madar, Tomer Illouz, Kathleen Griffioen, Israel Steiner, Daniel Offen, Eitan Okun
OBJECTIVE: Epilepsy affects 60 million people worldwide. Despite the development of antiepileptic drugs, up to 35% of patients are drug refractory with uncontrollable seizures. Toll-like receptors (TLRs) are central components of the nonspecific innate inflammatory response. Because TLR3 was recently implicated in neuronal plasticity, we hypothesized that it may contribute to the development of epilepsy after status epilepticus (SE). METHODS: To test the involvement of TLR3 in epileptogenesis, we used the pilocarpine model for SE in TLR3-deficient mice and their respective wild-type controls...
February 6, 2017: Epilepsia
https://www.readbyqxmd.com/read/28166277/ketogenic-diet-improves-behaviors-in-a-maternal-immune-activation-model-of-autism-spectrum-disorder
#13
David N Ruskin, Michelle I Murphy, Sierra L Slade, Susan A Masino
Prenatal factors influence autism spectrum disorder (ASD) incidence in children and can increase ASD symptoms in offspring of animal models. These may include maternal immune activation (MIA) due to viral or bacterial infection during the first trimesters. Unfortunately, regardless of ASD etiology, existing drugs are poorly effective against core symptoms. For nearly a century a ketogenic diet (KD) has been used to treat seizures, and recent insights into mechanisms of ASD and a growing recognition that immune/inflammatory conditions exacerbate ASD risk has increased interest in KD as a treatment for ASD...
2017: PloS One
https://www.readbyqxmd.com/read/28163500/an-analytical-study-to-correlate-serum-levels-of-levetiracetam-with-clinical-course-in-patients-with-epilepsy
#14
Varun Gupta, Kanchan Gupta, Gagandeep Singh, Sandeep Kaushal
INTRODUCTION: With the advancement of therapeutics, newer antiepileptic drugs (AEDs) like Levetiracetam (LEV), with good therapeutic efficacy and tolerability are available. But unfortunately, therapeutic drug monitoring is not routinely done in India for these drugs. OBJECTIVES: The objective of this study is to determine the range of serum levels of LEV in patients at stabilized doses and correlate them with their clinical course. MATERIALS AND METHODS: Patients with epilepsy and started on LEV were enrolled from the Neurology Department after the Ethics Committee approval...
December 2016: Journal of Neurosciences in Rural Practice
https://www.readbyqxmd.com/read/28155226/propofol-versus-thiopental-sodium-for-the-treatment-of-refractory-status-epilepticus
#15
REVIEW
Hemanshu Prabhakar, Mani Kalaivani
BACKGROUND: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 6, 2015).Failure to respond to antiepileptic drugs in patients with uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective...
February 3, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28131532/high-frequency-spectral-changes-induced-by-single-pulse-electric-stimulation-comparison-between-physiologic-and-pathologic-networks
#16
Mihai Dragos Mălîia, Cristian Donos, Andrei Barborica, Ioana Mindruta, Irina Popa, Mirela Ene, Sándor Beniczky
OBJECTIVE: To investigate functional coupling between brain networks using spectral changes induced by single-pulse electric stimulation (SPES). METHOD: We analyzed 20 patients with focal epilepsy, implanted with depth electrodes. SPES was applied to each pair of adjacent contacts, and responses were recorded from all other contacts. The mean response amplitude value was quantified in three time-periods after stimulation (10-60, 60-255, 255-500ms) for three frequency-ranges (Gamma, Ripples, Fast-Ripples), and compared to baseline...
December 28, 2016: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/28129943/beta-site-amyloid-precursor-protein-cleaving-enzyme-1-inhibition-impairs-synaptic-plasticity-via-seizure-protein-6
#17
Kaichuan Zhu, Xianyuan Xiang, Severin Filser, Petar Marinković, Mario M Dorostkar, Sophie Crux, Ulf Neumann, Derya R Shimshek, Gerhard Rammes, Christian Haass, Stefan F Lichtenthaler, Jenny M Gunnersen, Jochen Herms
BACKGROUND: Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a promising drug target for the treatment of Alzheimer's disease. Prolonged BACE1 inhibition interferes with structural and functional synaptic plasticity in mice, most likely by altering the metabolism of BACE1 substrates. Seizure protein 6 (SEZ6) is predominantly cleaved by BACE1, and Sez6 knockout mice share some phenotypes with BACE1 inhibitor-treated mice. We investigated whether SEZ6 is involved in BACE1 inhibition-induced structural and functional synaptic alterations...
December 26, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/28125507/behavioural-effects-of-novel-multitarget-anticholinesterasic-derivatives-in-alzheimer-s-disease
#18
Lydia Giménez-Llort, Miriam Ratia, Belén Pérez, Pelayo Camps, Diego Muñoz-Torrero, Albert Badia, Maria V Clos
The current pharmacological approach to Alzheimer's disease (AD) treatment, mostly based on acetylcholinesterase inhibitors (AChEIs), is being revisited, especially in terms of the temporal frames and the potential benefits of their noncanonic actions, raising the question of whether inhibitors of AChE might also act in a disease-modifying manner. Besides, in the last decades, the pharmacophoric moieties of known AChEIs have been covalently linked to other pharmacophores in the pursuit of multitarget hybrid molecules that are expected to induce long-lasting amelioration of impaired neurotransmission and clinical symptoms but also to exert disease-modifying effects...
January 25, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28125041/synthesis-modelling-and-anticonvulsant-studies-of-new-quinazolines-showing-three-highly-active-compounds-with-low-toxicity-and-high-affinity-to-the-gaba-a-receptor
#19
Mohamed F Zayed, Saleh K Ihmaid, Hany E A Ahmed, Khaled El-Adl, Ahmed M Asiri, Abdelsattar M Omar
Some novel fluorinated quinazolines (5a-j) were designed and synthesized to be evaluated for their anticonvulsant activity and their neurotoxicity. Structures of all newly synthesized compounds were confirmed by their infrared (IR), mass spectrometry (MS) spectra, ¹H nuclear magnetic resonance (NMR), (13)C-NMR, and elemental analysis (CHN). The anticonvulsant activity was evaluated by a subcutaneous pentylenetetrazole (scPTZ) test and maximal electroshock (MES)-induced seizure test, while neurotoxicity was evaluated by a rotorod test...
January 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28118493/anticonvulsant-effect-of-sodium-cyclamate-and-propylparaben-on-pentylenetetrazol-induced-seizures-in-zebrafish
#20
Antonella Pisera-Fuster, Sofía Otero, Alan Talevi, Luis Bruno-Blanch, Ramón Bernabeu
Screening for novel anticonvulsant drugs requires appropriate animal seizure models. Zebrafish provide small, accessible, and cost-efficient preclinical models applicable to high-throughput small molecule screening. Based on previous results in rodents, we have here examined the effects of artificial sweetener sodium cyclamate and antimicrobial agent sodium propylparaben on a model of pentylenetetrazole (PTZ)-induced seizures in zebrafish. Sodium cyclamate reduced the bursts of hyperactivity, the spasms, increased the latency to spasms, and the latency to seizure, while propylparaben increased the latency to spasms...
April 2017: Synapse
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