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Heidy Martínez-Pacheco, Guillermo Ramírez-Galicia, Midalia Vergara-Arias, Jürg Gertsch, Jonathan Manuel Fragoso-Vázquez, David Méndez-Luna, A L Abujamra, Cabrera-Pérez Laura Cristina, Rosales-Hernández Martha Cecilia, I Mendoza-Lujambio, José Correa-Basurto
Histone deacetylase 8 (HDAC8) is a plausible target for the development of novel anticancer drugs using a metal-chelating group and hydrophobic moieties as pharmacophores. It is known that valproic acid (administered as its salt, sodium valproate; VPANa+) is an HDAC8 inhibitor characterized by its hydrophobic chains. Nevertheless, VPA is hepatotoxic and VPA analogues might be explored for less hepatotoxic antiproliferative compounds. In this work, docking and QSAR studies of 500 aryl-VPA derivatives as possible HDAC8 inhibitors were performed in order to explore and select potential anti-proliferative compounds...
October 19, 2016: Anti-cancer Agents in Medicinal Chemistry
Paresh Zanzmera, Ramshekhar N Menon, Kalyani Karkare, Himanshu Soni, Sujit Jagtap, Ashalatha Radhakrishnan
PURPOSE: The purpose of this article was to study the electroclinical characteristics and seizure outcome of children with epilepsy with myoclonic absences (EMA). METHOD: In this descriptive cohort study, we reviewed clinical records of patients who met the criteria for EMA. Each patient's demographic data, birth/developmental history, seizure semiology/pattern, antiepileptic drugs (AED), clinical examination, video-electroencephalography (VEEG), and neuroimaging data were reviewed...
October 19, 2016: Epilepsy & Behavior: E&B
Hiroko Kubo, Masahito Nakataki, Satsuki Sumitani, Jun-Ichi Iga, Shusuke Numata, Naomi Kameoka, Shin-Ya Watanabe, Hidehiro Umehara, Makoto Kinoshita, Masatoshi Inoshita, Mai Tamaru, Masashi Ohta, Chiaki Nakayama-Yamauchi, Yasuhiro Funakoshi, Masafumi Harada, Tetsuro Ohmori
BACKGROUND: Previous studies of patients with bipolar disorder (BD) using magnetic resonance spectroscopy (MRS) have shown neurophysiological abnormalities related to the glutamate (Glu)-glutamine (Gln) cycle, membrane turnover, and neuronal integrity, although the results were neither consistent nor conclusive. Recently it has been reported the Gln/Glu ratio is the most useful index, quantifying neuronal-glial interactions and the balance of glutamatergic metabolites In this MRS study, we elucidated the abnormalities of metabolites in a larger sample of patients with BD with a high-field MRI system...
October 8, 2016: Journal of Affective Disorders
Kenichiro Sato, Noritoshi Arai, Aki Omori, Ayumi Hida, Akio Kimura, Sousuke Takeuchi
PURPOSE: Hyperammonaemia is frequently observed in patients who have experienced convulsive seizures. Although excessive muscle contraction is presumed to be responsible for the elevated levels of ammonia, the underlying mechanism is poorly understood. The present study aimed to identify the independent factors associated with ammonia elevation using large-scale multivariate analysis. METHODS: We conducted a cross-sectional study involving 379 adult patients who had been transported to our emergency department and treated for unprovoked convulsive seizures between August 2010 and September 2015...
October 6, 2016: Seizure: the Journal of the British Epilepsy Association
Kei Itagaki, Minoru Takebayashi, Chiyo Shibasaki, Naoto Kajitani, Hiromi Abe, Mami Okada-Tsuchioka, Shigeto Yamawaki
BACKGROUND: While electroconvulsive therapy (ECT) treatment for depression is highly effective, the high rate of relapse is a critical problem. The current study investigated factors associated with the risk of relapse in mood disorders in patients in which ECT was initially effective. METHOD: The records of 100 patients with mood disorders (61 unipolar depression, 39 bipolar depression) who received and responded to an acute ECT course were retrospectively reviewed...
October 11, 2016: Journal of Affective Disorders
Jeroen G V Habets, Albert F G Leentjens, Olaf E M G Schijns
Levetiracetam may induce serious behavioral disturbances, especially after surgical resection of frontal lobe low-grade glioma. Two patients, treated with levetiracetam, developed serious psychiatric complications postoperatively which completely resolved after switching to valproate. We aim to create awareness for this serious but reversible adverse effect of levetiracetam in this specific patient category.
October 20, 2016: British Journal of Neurosurgery
U C Wieshmann, G Baker
OBJECTIVE: To ascertain efficacy and tolerability of carbamazepine (CBZ), sodium valproate (VPA), lamotrigine (LTG) and levetiracetam (LEV) using the UKAED register ( METHODS: Patients on CBZ (n=91), VPA (n=61), LTG (n=105), LEV (n=72) and healthy control subjects (CTR) on no medication (n=51) were extracted. All patients had anonymously provided information on seizure type and frequency and completed the Liverpool Adverse Event Profile (LAEP). RESULTS: The number of seizure-free patients in the last 4 weeks was overall CBZ/VPA/LTG/LEV=60%/79%/67%/67%, for generalized epilepsy was CBZ/VPA/LTG/LEV=67%/89%/65%/94%, and for localization-related epilepsy was CBZ/VPA/LTG/LEV=59%/71%/67%/57%...
October 18, 2016: Acta Neurologica Scandinavica
Garima Shukla, Anupama Gupta, Priya Agarwal, Shivani Poornima
PURPOSE: Levetiracetam (LEV) is often chosen early in the treatment of refractory epilepsy; however, its adverse effects have largely been studied as part of clinical trials. Oxcarbazepine and valproate (VPA) are the other commonly used AEDs and, hence, serve as good comparators. This study was conducted to evaluate behavioral abnormalities and somnolence among patients with epilepsy being treated with LEV and/or OXC compared with those receiving VPA. METHOD: Data of consecutive patients attending our intractable epilepsy clinic over a 2 1/2-year period were reviewed, and patients with at least one seizure a month, who had been initiated on either or a combination of LEV, VPA, or OXC, were included for analysis...
October 15, 2016: Epilepsy & Behavior: E&B
Terence A Ketter, Suresh Durgam, Ronald Landbloom, Mary Mackle, Xiao Wu, Maju Mathews
BACKGROUND: Asenapine (ASN) is approved in the United States as monotherapy and adjunctive therapy (to lithium or valproate) in adults with bipolar mania, and as monotherapy in pediatric patients with bipolar mania. This is the first long-term study evaluating safety and tolerability of ASN fixed doses in this population. METHODS: After completing a 3-week, randomized, placebo (PBO)-controlled acute trial, patients could enroll in this 26-week, fixed-dose (5 or 10mg twice daily), double-blind extension study...
October 14, 2016: Journal of Affective Disorders
Vincenzo De Iuliis, Raimondo Gelormini, Mariarosaria Flacco, Giuseppe Moriello, Marika Caruso, Eugenia Barone, Maria Golato, Elena Toniato, Pio Conti, Stefano Martinotti
BACKGROUND: Valproate is a broad-spectrum anticonvulsant that is effective in the treatment of tonic-clonic, myoclonic and absence seizures as well as in partial seizures as a second-line drug. It has been widely demonstrated in the literature that the effect of valproate on type-A γ-aminobutyric acid (GABA-A) receptors may reduce relapse to ethanol abuse. This retrospective study evaluated a 3-year period in which 42 patients from the Department of Alcoholism and Substance Abuse (DASA) were treated with valproate...
March 2016: Drugs—Real World Outcomes
Huimin Lin, Samuel T H Chew
An 85-year-old female with chronic kidney disease and newly acquired seizures on oral phenytoin received intravenous ertapenem 500 mg once daily for a urinary tract infection and bacteraemia involving extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. After three ertapenem doses, she developed seizures which self-aborted. Corrected phenytoin level was sub-therapeutic initially, but became therapeutic following a phenytoin dose increase. On Day 14 of ertapenem, the patient suffered another episode of seizure...
December 2015: Drug Saf Case Rep
Melania Olivieri, Emanuele Amata, Shila Vinciguerra, Jole Fiorito, Giovanni Giurdanella, Filippo Drago, Nunzia Caporarello, Orazio Prezzavento, Emanuela Arena, Loredana Salerno, Antonio Rescifina, Gabriella Lupo, Carmelina Daniela Anfuso, Agostino Marrazzo
(±)-MRJF22 [(±)-2], a novel prodrug of haloperidol metabolite II obtained by conjugation to valproic acid via an ester bond, exhibits antiangiogenic activity being able to reduce Human Retinal Endothelial Cells (HREC) viability in a comparable manner to Bevacizumab. Moreover, (±)-2 was able to significantly reduce viable cells count, endothelial cell migration and tube formation in Vascular endothelial growth factor A (VEGF-A) stimulated HREC cultures.
October 14, 2016: Journal of Medicinal Chemistry
Elham Kordijaz, Ali Moghimi, Masoud Fereidoni, Saeedeh Asadi, Ali Shamsizadeh, Ali Roohbakhsh
Convulsive seizures are due to abnormal synchronous and repetitive neuronal discharges in the central nervous system (CNS). Finding new therapeutics to overcome the side effects of the current drug therapies and to increase their effectiveness is ongoing. Orexin-A and orexin-B are brain neuropeptides originating from postero-lateral hypothalamic neurons. Studies show that orexins, through activation of OX1 and OX2 receptors, have excitatory effects in the CNS. Accordingly, the present study was designed to evaluate the effect of OX1 receptor antagonist (SB-334867) on seizure- and anxiety-related behaviors of pentylenetetrazol (PTZ) kindled rats...
October 14, 2016: Fundamental & Clinical Pharmacology
Xi Lu, Xuefeng Wang
Hyponatremia induced by antiepileptic drugs (AEDs) has not received sufficient attention in patients with epilepsy. Areas covered: We reviewed articles between 1966 and 2015 about hyponatremia as an adverse effect of AEDs in patients with epilepsy. The incidence, clinical symptoms, onset times of AEDs-induced hyponatremia are discussed in detail, as are the risk factors associated with AEDs-induced hyponatremia and mechanisms underlying its development. We also briefly describe strategies for treating AED-induced hyponatremia...
October 13, 2016: Expert Opinion on Drug Safety
M Lambert, V Niehaus, C Correll
This review aims to describe the importance of i) detecting individuals at clinical high-risk for psychosis (schizophrenia) or bipolar disorder, especially in children and adolescents, in order to enable early intervention, and ii) evaluating different intervention strategies, especially pharmacotherapy, during the subsyndromal or "prodromal" stages of these severe and often debilitating disorders. The different approaches regarding the psychotic and bipolar clinical high-risk state are discussed, including reasons and evidence for early (pharmacological) intervention and risks of treatment vs...
October 13, 2016: Pharmacopsychiatry
Francesco Brigo, Nicola Bragazzi, Raffaele Nardone, Eugen Trinka
AIM: The aim of this study was to conduct a meta-analysis of published studies to directly compare intravenous (IV) levetiracetam (LEV) with IV phenytoin (PHT) or IV valproate (VPA) as second-line treatment of status epilepticus (SE), to indirectly compare intravenous IV LEV with IV VPA using common reference-based indirect comparison meta-analysis, and to verify whether results of indirect comparisons are consistent with results of head-to-head randomized controlled trials (RCTs) directly comparing IV LEV with IV VPA...
October 10, 2016: Epilepsy & Behavior: E&B
A G Kalacheva, O A Gromova, T R Grishina, I V Gogoleva, V I Demidov, I Yu Torshin
AIM: To study the micronutrients that potentiate the action of anticonvulsant drugs, and in particular, of myo-inositol (vitamin B8). MATERIAL AND METHODS: An experimental study of neurotrophic and anticonvulsant effects of a preparation based on myo-inositol (inofert) on thiosemicarbazide models of seizures was carried out. RESULTS: Inofert significantly increased the latent time before the first convulsive seizure, reduced the severity of seizures (p<0...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
T Ravindran, Paneerselvam, Radha, T Allwyn Yabesh
Osmotic demyelination syndrome is an acute shift in serum osmolality causing demyelination, which may be due to rapid correction of hyponatremia, hyperglycaemia, hypokalemia and ketoacidosis. We present a case of 55yr old female and a known diabetic presented with the choreic movements involving left upper and lower limb for 2 days without any weakness.Her blood sugar was 428mg/dl at the time of admission with wide fluctuations.Her CT Brain showed hyperdensity in the right basal ganglia and the MRI brain showed hyperintense lesion in T2 weighted images showing features suggestive of osmotic demyelination...
April 2016: Journal of the Association of Physicians of India
Bing Zhang, Jia-Wei Zhang, Wei-Ping Wang, Rui-Fang Dong, Shuang Tian, Chao Zhang
PURPOSE: Lamotrigine (LTG) is a broad-spectrum antiepileptic drug that is widely used in clinic. However, the effect of LTG on cognition and neurodegeneration during epilepsy treatment remains controversial. In this study, we compared the cognitive effects of LTG and sodium valproate in pentylenetetrazole (PTZ)-kindled animal model, and the dose dependency was tested for LTG. METHODS: PTZ-kindled animals were divided into the following treatment groups: control group, treated with 3...
October 12, 2016: Synapse
Mari Videman, Susanna Stjerna, Reina Roivainen, Taina Nybo, Sampsa Vanhatalo, Eija Gaily, Jukka M Leppänen
INTRODUCTION: Prenatal antiepileptic drug (AED) exposure is associated with an increased risk of cognitive impairment and autism spectrum disorders detected mainly at the age of two to six years. We examined whether the developmental aberrations associated with prenatal AED exposure could be detected already in infancy and whether effects on visual attention can be observed at this early age. MATERIAL AND METHODS: We compared a prospective cohort of infants with in utero exposure to AED (n=56) with infants without drug exposures (n=62)...
October 9, 2016: Epilepsy & Behavior: E&B
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