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https://www.readbyqxmd.com/read/27899394/stress-activated-kinase-mkk7-governs-epigenetics-of-cardiac-repolarization-for-arrhythmia-prevention
#1
Sanjoy K Chowdhury, Wei Liu, Min Zi, Yatong Li, Shunyao Wang, Hoyee Tsui, Sukhpal Prehar, Simon J Castro, Henggui Zhang, Yong Ji, Xiuqin Zhang, Rui-Ping Xiao, Rongli Zhang, Ming Lei, Lukas Cyganek, Kaomei Guan, Catherine B Millar, Xudong Liao, Mukesh K Jain, Mark R Boyett, Elizabeth J Cartwright, Holly A Shiels, Xin Wang
BACKGROUND: -Ventricular arrhythmia is a leading cause of cardiac mortality. Most antiarrhythmics present paradoxical pro-arrhythmic side effects, culminating in a greater risk of sudden death. METHODS: -We describe a new regulatory mechanism linking mitogen-activated kinase kinase-7 (MKK7) deficiency with increased arrhythmia vulnerability in hypertrophied and failing hearts using mouse models harbouring MKK7 knockout or overexpression. The human relevance of this arrhythmogenic mechanism is evaluated in human induced pluripotent stem cells-derived cardiomyocytes (iPSC-CMs)...
November 29, 2016: Circulation
https://www.readbyqxmd.com/read/27887842/simple-n-n-dimethyl-phenylsulfonamides-show-potent-anticonvulsant-effect-in-two-standard-epilepsy-models
#2
Tomoyuki Tanaka, Nana Yajima, Tomoko Kiyoshi, Yoshiki Miura, Seiji Iwama
Optimization of the previously reported benzothiazine analogue A led to the identification of compound 1, which showed anti-convulsant activity in two golden standard animal models of seizure, the MES and scPTZ models. Structure-activity relationship investigation of compound 1 revealed compounds 2, 6 and 19 as attractive anti-epileptic drug (AED) candidates with potent anticonvulsant effect in both the MES and scPTZ models. As these compounds are structurally different from existing AEDs, determination of their mechanism of actions could provide clues to understanding current therapy-resistant seizures...
November 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27884140/phase-ii-clinical-study-of-valproic-acid-plus-cisplatin-and-cetuximab-in-recurrent-and-or-metastatic-squamous-cell-carcinoma-of-head-and-neck-v-chance-trial
#3
Francesco Caponigro, Elena Di Gennaro, Franco Ionna, Francesco Longo, Corrado Aversa, Ettore Pavone, Maria Grazia Maglione, Massimiliano Di Marzo, Paolo Muto, Ernesta Cavalcanti, Antonella Petrillo, Fabio Sandomenico, Piera Maiolino, Roberta D'Aniello, Gerardo Botti, Rossella De Cecio, Nunzia Simona Losito, Stefania Scala, Annamaria Trotta, Andrea Ilaria Zotti, Francesca Bruzzese, Antonio Daponte, Ester Calogero, Massimo Montano, Monica Pontone, Gianfranco De Feo, Francesco Perri, Alfredo Budillon
BACKGROUND: Recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) has a poor prognosis and the combination of cisplatin and cetuximab, with or without 5-fluorouracil, is the gold standard treatment in this stage. Thus, the concomitant use of novel compounds represents a critical strategy to improve treatment results. Histone deacetylase inhibitors (HDACi) enhance the activity of several anticancer drugs including cisplatin and anti-Epidermal Growth Factor Receptor (anti-EGFR) compounds...
November 25, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27882170/acute-encephalitis-with-refractory-repetitive-partial-seizures-a-case-report-and-literature-review
#4
Bin Zhang, Lin Wang
A male 46 year-old patient was admitted to the Emergency Intensive Care Unit of Qinghai Provincial People's Hospital (Xining, China) in December 2008 with complaints of a headache and fever that had lasted for three days. In addition, the patient had experienced two general convulsions accompanied with consciousness disorders for 7 h. Although the patient's clinical manifestations, laboratory tests and cerebrospinal fluid examinations were consistent with numerous features associated with acute encephalitis, the patient's clinical course was different to that of acute encephalitis, and the prognosis was poor...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27875769/status-epilepticus-in-pregnant-women-with-epilepsy-after-valproate-adjustment-a-case-series
#5
Mengqian Wu, Nanya Hao, Bo Yan, Xiaosa Chi, Dong Zhou
PURPOSE: Valproate is an effective wide-spectrum anti-epileptic drug that is also known to be teratogenic. Its administration in epileptic women remains controversial. This report aims to draw more attention to valproate adjustment before and during pregnancy. METHODS: We collected medical records of pregnant women with epilepsy at West China Hospital in Chengdu, China who developed status epilepticus during pregnancy after valproate withdrawal or reduction in dose from January 2013 to July 2015...
November 14, 2016: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/27868454/the-atp-sensitive-k-channel-is-seizure-protective-and-required-for-effective-dietary-therapy-in-a-model-of-mitochondrial-encephalomyopathy
#6
Keri J Fogle, J Ian Hertzler, Joy H Shon, Michael J Palladino
Effective therapies are lacking for mitochondrial encephalomyopathies (MEs). MEs are devastating diseases that predominantly affect the energy-demanding tissues of the nervous system and muscle, causing symptoms such as seizures, cardiomyopathy, and neuro- and muscular degeneration. Even common anti-epileptic drugs which are frequently successful in ameliorating seizures in other diseases tend to have a lower success rate in ME, highlighting the need for novel drug targets, especially those that may couple metabolic sensitivity to neuronal excitability...
November 21, 2016: Journal of Neurogenetics
https://www.readbyqxmd.com/read/27861722/epilepsy-and-adverse-quality-of-life-in-surgically-resected-meningioma
#7
M J Tanti, A G Marson, M D Jenkinson
OBJECTIVES: Meningiomas are common intracranial tumors, and despite surgery or therapy with anti-epileptic drugs (AEDs), many patients suffer from seizures. Epilepsy has a significant impact on quality of life (QoL) in non-tumor populations, but the impact of epilepsy on QoL in patients with meningioma is unknown. Our aim was to evaluate the impact of epilepsy on QoL in patients that have undergone resection of a benign meningioma. MATERIALS AND METHODS: We recruited meningioma patients without epilepsy (n=109), meningioma patients with epilepsy (n=56), and epilepsy patients without meningioma (n=64)...
November 14, 2016: Acta Neurologica Scandinavica
https://www.readbyqxmd.com/read/27861538/development-and-validation-of-a-new-mouse-model-to-investigate-the-role-of-sv2a-in-epilepsy
#8
Catherine Menten-Dedoyart, Maria Elisa Serrano Navacerrada, Odile Bartholome, Judit Sánchez Gil, Virginie Neirinckx, Sabine Wislet, Guillaume Becker, Alain Plenevaux, Priscilla Van den Ackerveken, Bernard Rogister
SV2A is a glycoprotein present in the membranes of most synaptic vesicles. Although it has been highly conserved throughout evolution, its physiological role remains largely unknown. Nevertheless, Levetiracetam, a very effective anti-epileptic drug, has been recently demonstrated to bind to SV2A. At present, our understanding of the normal function of SV2A and its possible involvement in diseases like epilepsy is limited. With this study, we sought to develop a relevant model enabling analysis of SV2A's role in the occurrence or progression of epilepsy...
2016: PloS One
https://www.readbyqxmd.com/read/27860117/development-of-a-core-outcome-set-for-epilepsy-in-pregnancy-e-core-a-national-multi-stakeholder-modified-delphi-consensus-study
#9
B H Al Wattar, K Tamilselvan, R Khan, A Kelso, A Sinha, A M Pirie, D McCorry, K S Khan, S Thangaratinam
OBJECTIVE: To develop a set of core outcomes for studies on pregnant women with epilepsy. DESIGN: Delphi consensus study. POPULATION: Healthcare professionals, and patient representatives with lived experience of epilepsy in the UK. METHODS: We used a modified Delphi method and a consultation meeting to achieve consensus. Potential outcomes were identified by systematic review, and were scored using a Likert scale anchored between 1 (least important) and 5 (most important)...
November 16, 2016: BJOG: An International Journal of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/27856333/novel-homozygous-missense-mutation-in-aldh7a1-causes-neonatal-pyridoxine-dependent-epilepsy
#10
Emanuele G Coci, Luca Codutti, Christian Fink, Sophie Bartsch, Gunnar Grüning, Thomas Lücke, Ingo Kurth, Joachim Riedel
Pyridoxine dependent epilepsy (PDE) (OMIM#266100) is a neonatal form of epilepsy, caused by dysfunction of the enzyme α-aminoadipic semialdehyde dehydrogenase (ALDH7A1 or Antiquitin). This enzyme converts α-aminoadipic semialdehyde (α-AASA) into α-aminoadipate (AAA), a critical step in the lysine metabolism of the brain. ALDH7A1 dysfunction causes an accumulation of α-AASA and δ(1)-piperideine-6-carboxylic acid (P6C), which are in equilibrium with each other. P6C binds and inactivates pyridoxal 5'-phosphate (PLP), the active form of pyridoxine...
November 14, 2016: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/27854111/the-risk-of-hypotension-and-seizures-in-patients-receiving-prophylactic-anti-epileptic-drugs-for-supratentorial-craniotomy
#11
Julius Höhne, Karl M Schebesch, Christian Ott, Alexander Brawanski, Max Lange
BACKGROUND: Perioperative seizure prophylaxis with antiepileptic drugs (AED) has been advocated in patients undergoing supratentorial craniotomy. The practice remains controversial. The reasoning presupposes that the possibility of an adverse drug reaction from the AED is lower than the probability of harm from a seizure. Even short periods of hypotension during the operation can lead to acute kidney and myocardial injury. We retrospectively evaluated cardiovascular effects and tolerability of Levetiracetam (LEV) alone, LEV and Lacosamid (LCM) as compared to Phenytoin (PHT)...
November 17, 2016: Journal of Neurosurgical Sciences
https://www.readbyqxmd.com/read/27854088/long-term-and-strong-immunotherapy-to-treat-anti-n-methyl-d-aspartate-receptor-encephalitis-with-refractory-status-epilepticus
#12
Lan-Hsin Lee, Chien-Jung Lu
BACKGROUND: Anti-N-Methyl-D-Aspartate receptor (anti-NMDAR) encephalitis is responsive to immunotherapy and removal of tumor, but there is no consensus in the treatment of severe anti- NMDAR encephalitis with prolonged refractory status epilepticus (SE). CASE REPORT: A 17-year-old girl presented as acute psychosis, refractory seizures, hyperkinesia, autonomic instability, and soon progressed to a dissociative state of coma. Anti-NMDAR antibodies were positive in serum and CSF...
September 15, 2016: Acta Neurologica Taiwanica
https://www.readbyqxmd.com/read/27843463/the-comparison-between-effect-of-chloralhydrate-and-diphenhydramine-on-sedating-for-electroencephalography
#13
Afagh Hassanzadeh Rad, Vahid Aminzadeh
OBJECTIVE: Electroencephalography (EEG) is the most effective diagnostic tool in distinguishing epileptic seizure. Chloral hydrate (CH) is a sedative hypnotic drug, commonly used as a method of sedation in children aged<3 yr. Furthermore, diphenhydramine (DH) is a first generation antihistaminic drug (H1 receptor blocker) with anti-cholinergic effect. In this study, we aimed to compare the effects of CH and DH on sedating for EEG. MATERIALS & METHODS: This retrospective cohort study was conducted on patients' records of aged 15-72 months undergone an EEG and required sedation...
2016: Iranian Journal of Child Neurology
https://www.readbyqxmd.com/read/27842767/drug-hepatotoxicity-newer-agents
#14
REVIEW
Chalermrat Bunchorntavakul, K Rajender Reddy
Idiosyncratic hepatotoxicity is one of the most common reasons for an approved drug being restricted. This article focuses on hepatotoxicity of selected and recently introduced agents, such as, tyrosine kinase inhibitors, monoclonal antibodies, novel oral anticoagulants, newer antiplatelets, antibiotics, anti-diabetics, anti-epileptics, anti-depressants, anti-psychotics and anti-retrovirals. Overall, the incidence of clinically relevant hepatotoxicity from newer agents seems to be lower than that of the older agents...
February 2017: Clinics in Liver Disease
https://www.readbyqxmd.com/read/27825017/a-pharmacological-overview-of-lamotrigine-for-the-treatment-of-epilepsy
#15
Venkata Ramesh Yasam, Satya Lavanya Jakki, V Senthil, M Eswaramoorthy, S Shanmuganathan, K Arjunan, M J Nanjan
Epilepsy is one of the most common neurological disorders, affecting about 2% of the population worldwide. Lamotrigine (LTG) is a second generation anti-epileptic drug (AED) with broad spectrum of activity, a favourable side-effect profile, simpler dosing than earlier drugs and efficacious in diverse epilepsy syndromes. Areas covered: The present review focuses on pharmacodynamics, pharmacokinetics, clinical efficacy, safety and tolerability of LTG and its effect on cognition, psychiatry, quality of life, women and pregnancy along with effect of enzyme inducing and enzyme inhibiting drugs over LTG and their effect on serum level fluctuations by collecting data from various studies over the years until 2016...
November 21, 2016: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/27824913/treatment-trials-for-neonatal-seizures-the-effect-of-design-on-sample-size
#16
Nathan J Stevenson, Geraldine B Boylan, Lena Hellström-Westas, Sampsa Vanhatalo
Neonatal seizures are common in the neonatal intensive care unit. Clinicians treat these seizures with several anti-epileptic drugs (AEDs) to reduce seizures in a neonate. Current AEDs exhibit sub-optimal efficacy and several randomized control trials (RCT) of novel AEDs are planned. The aim of this study was to measure the influence of trial design on the required sample size of a RCT. We used seizure time courses from 41 term neonates with hypoxic ischaemic encephalopathy to build seizure treatment trial simulations...
2016: PloS One
https://www.readbyqxmd.com/read/27823573/the-sphingosine-1-phosphate-signaling-pathway-in-epilepsy-a-possible-role-for-the-immunomodulator-drug-fingolimod-in-epilepsy-treatment
#17
Antonio Leo, Rita Citraro, Rosario Marra, Ernesto Palma, Eugenio Donato Di Paola, Andrew Constanti, Giovambattista De Sarro, Emilio Russo
It is currently known that erythrocytes are the major source of sphingosine 1-phosphate (S1P) in the body. S1P acts both extracellularly as a cellular mediator and intracellularly as an important second messenger molecule. Its effects are mediated by interaction with five specific types of G protein-coupled S1P receptor. Fingolimod, is a recognized modulator of S1P receptors, and is the first orally active disease-modifying therapy that has been approved for the treatment of multiple sclerosis. Magnetic resonance imaging data suggest that fingolimod may be effective in multiple sclerosis MS by preventing blood-brain barrier disruption and brain atrophy...
November 4, 2016: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/27816347/cerebral-venous-thrombosis
#18
José Manuel Ferro, Patrícia Canhão, Diana Aguiar de Sousa
Cerebral venous thrombosis (CVT) has an incidence of 1.32/100,000/years in high-income countries, and higher in middle- and low-income countries. CVT is more frequent in infants and children young adults and females, especially during pregnancy/puerperium. CVT are now being diagnosed with increasing frequency because of the increased awareness and higher use of magnetic resonance imaging (MR) for investigating patients with acute and subacute headaches and new onset seizures. CVT rarely present as a stroke syndrome...
November 2, 2016: La Presse Médicale
https://www.readbyqxmd.com/read/27812327/social-preference-deficits-in-juvenile-zebrafish-induced-by-early-chronic-exposure-to-sodium-valproate
#19
Xiuyun Liu, Yinglan Zhang, Jia Lin, Qiaoxi Xia, Ning Guo, Qiang Li
Prenatal exposure to sodium valproate (VPA), a widely used anti-epileptic drug, is related to a series of dysfunctions, such as deficits in language and communication. Clinical and animal studies have indicated that the effects of VPA are related to the concentration and to the exposure window, while the neurobehavioral effects of VPA have received limited research attention. In the current study, to analyze the neurobehavioral effects of VPA, zebrafish at 24 h post-fertilization (hpf) were treated with early chronic exposure to 20 μM VPA for 7 h per day for 6 days or with early acute exposure to 100 μM VPA for 7 h...
2016: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/27790929/allele-and-genotype-frequencies-of-genes-relevant-to-anti-epileptic-drug-therapy-in-mexican-mestizo-healthy-volunteers
#20
Ingrid Fricke-Galindo, Alberto Ortega-Vázquez, Nancy Monroy-Jaramillo, Pedro Dorado, Helgi Jung-Cook, Eva Peñas-Lledó, Adrián LLerena, Marisol López-López
AIM: To determine allele and genotype frequencies of genes influencing anti-epileptic drug therapy in Mexican-Mestizo (MM) healthy volunteers, and to evaluate whether these are different from those reported for other populations. SUBJECTS & METHODS: Thirty-nine variants of CYP3A5, EPHX1, NR1I2, HNF4A, UGT1A1, UGT2B7, ABCC2, RALBP1, SCN1A, SCN2A and GABRA1 were genotyped in 300 MM healthy volunteers. RESULTS: All studied alleles were presented in MM, except for seven UGT1A1 variants (*6-8, 14, 15, 27 and 29)...
October 28, 2016: Pharmacogenomics
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