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https://www.readbyqxmd.com/read/29427834/safety-of-antiepileptic-drugs-in-children-and-young-people-a-prospective-cohort-study
#1
Oluwaseun Egunsola, Imti Choonara, Helen M Sammons, William P Whitehouse
PURPOSE: This study aims to describe the incidence of adverse drug reactions (ADRs) in children receiving antiepileptic drugs (AEDs) and compare ADRs to the individual drugs when given as monotherapy. METHOD: Paediatric patients (≤18 years old) were enrolled for this prospective observational study over a 6-month period, between September 2015 and March 2016. Adverse reactions to antiepileptic drugs (AEDs) were elicited at the time of enrolment and after 3 months using the Paediatric Epilepsy Side Effects Questionnaire...
February 2, 2018: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/29403264/anticonvulsant-and-reproductive-toxicological-studies-of-the-imidazole-based-histamine-h3r-antagonist-2-18-in-mice
#2
Salim M Bastaki, Yousef M Abdulrazzaq, Mohamed Shafiullah, Małgorzata Więcek, Katarzyna Kieć-Kononowicz, Bassem Sadek
The imidazole-based H3R antagonist 2-18 with high in vitro H3R antagonist affinity, excellent in vitro selectivity profile, and high in vivo H3R antagonist potency was tested for its anticonvulsant effect in maximal electroshock (MES)-induced convulsions in mice having valproic acid (VPA) as a reference antiepileptic drug (AED). Additionally, H3R antagonist 2-18 was evaluated for its reproductive toxicity in the same animal species. The results show that acute systemic administration (intraperitoneal; i.p.) of H3R antagonist 2-18 (7...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29363050/effect-of-age-related-factors-on-the-pharmacokinetics-of-lamotrigine-and-potential-implications-for-dose-optimisation-in-epilepsy-patients
#3
Sven C van Dijkman, Nico C B de Jager, Willem M Rauwé, Meindert Danhof, Oscar Della Pasqua
BACKGROUND AND AIMS: In this study, we evaluate the performance of allometric concepts to predict the implications of age and size on the pharmacokinetics of lamotrigine, and assess the dose rationale across different age groups from 0.2 to 91 years. METHODS: An allometrically scaled pharmacokinetic model was developed using adolescent and adult data, taking into account the effect of comedications. Model parameters were then used to extrapolate lamotrigine pharmacokinetics to older adults (> 65 years), children (4-12 years) and infants and toddlers (0...
January 23, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29343446/s-adenosyl-methionine-prevents-asd-like-behaviors-triggered-by-early-postnatal-valproic-acid-exposure-in-very-young-mice
#4
Asher Ornoy, Liza Weinstein-Fudim, Matanel Tfilin, Zivanit Ergaz, Joseph Yanai, Moshe Szyf, Gadi Turgeman
INTRODUCTION: A common animal model of ASD is the one induced by valproic acid (VPA), inducing epigenetic changes and oxidative stress. We studied the possible preventive effect of the methyl donor for epigenetic enzymatic reactions, S-adenosine methionine (SAM), on ASD like behavioral changes and on redox potential in the brain and liver in this model. METHODS: ICR albino mice were injected on postnatal day 4 with one dose of 300 mg/kg of VPA, with normal saline (controls) or with VPA and SAM that was given orally for 3 days at the dose of 30 mg/kg body weight...
January 14, 2018: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/29340733/population-pharmacokinetics-of-lamotrigine-co-administered-with-valproic-acid-in-chinese-epileptic-children-using-nonlinear-mixed-effects-modeling
#5
Shansen Xu, Limin Liu, Yanan Chen, Mei Liu, Tong Lu, Huanxin Wang, Shihao Liu, Mingming Zhao, Limei Zhao
PURPOSE: The aims of this study were to develop a population pharmacokinetic (PPK) model of lamotrigine (LTG) in Chinese epileptic children by using nonlinear mixed effects modeling (NONMEM) and to investigate the effects of valproic acid (VPA) and genetic polymorphisms of the major metabolizing enzymes (UGT1A4, UGT2B7) on the pharmacokinetics of LTG. METHODS: A total of 182 epileptic children who were treated with LTG as monotherapy or as part of combination therapy were included in this study as the model group, and 61 patients were included as the validation group...
January 16, 2018: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29328514/a-systematic-review-of-population-pharmacokinetics-of-valproic-acid
#6
Janthima Methaneethorn
AIMS: Population pharmacokinetics is an essential tool that helps guiding individualized dosing regimens. The aims of this systematic review are to provide knowledge concerning population pharmacokinetics of valproic acid (VPA) and to identify factors influencing VPA pharmacokinetic variability. METHODS: Pubmed and Embase databases were systematically searched from inception to June, 2017. Relevant articles from reference lists were also included. All population pharmacokinetic studies of VPA conducted in human and employed nonlinear mixed effect modeling approach were included in this review...
January 12, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29229235/valproic-acid-disrupts-the-oscillatory-expression-of-core-circadian-rhythm-transcription-factors
#7
Chanel A Griggs, Scott W Malm, Rosa Jaime-Frias, Catharine L Smith
Valproic acid (VPA) is a well-established therapeutic used in treatment of seizure and mood disorders as well as migraines and a known hepatotoxicant. About 50% of VPA users experience metabolic disruptions, including weight gain, hyperlipidemia, and hyperinsulinemia, among others. Several of these metabolic abnormalities are similar to the effects of circadian rhythm disruption. In the current study, we examine the effect of VPA exposure on the expression of core circadian transcription factors that drive the circadian clock via a transcription-translation feedback loop...
December 8, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29143997/epidermal-neural-crest-stem-cell-derived-glia-enhance-neurotrophic-elements-in-an-ex-vivo-model-of-spinal-cord-injury
#8
Sareh Pandamooz, Mohammad Saied Salehi, Mohammad Ismail Zibaii, Abolhassan Ahmadiani, Mohammad Nabiuni, Leila Dargahi
Growing evidence that cell-based therapies can improve recovery outcome in spinal cord injury (SCI) models substantiates their application for treatment of human with SCI. To address the effectiveness of these stem cells, potential candidates should be evaluated in proper SCI platform that allows direct real-time monitoring. In this study, the role of epidermal neural crest stem cells (EPI-NCSCs) was elucidated in an ex vivo model of SCI and valproic acid (VPA) was administered to ameliorate the inhospitable context of injury for grafted EPI-NCSCs...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29076421/seizures-and-anticonvulsants-in-brain-tumours-frequency-mechanisms-and-anti-epileptic-management
#9
Charles Vecht, Louis Royer-Perron, Caroline Houillier, Gilles Huberfeld
In cancer, epilepsy can be the manifestation of a primary brain tumour, metastatic disease, vascular or surgical complications, opportunistic infection or secondary to anti-tumour therapy. Seizures are frequently the first symptom of a brain tumour. The epilepsy is related to elevated extracellular glutamate stimulating NMDA- and AMPA-receptors and to the formation of D-2HG which resembles glutamate in IDH1 mutated gliomas. Epilepsy as presenting sign is associated with a longer survival in low- and high- grade gliomas, particularly with the IDH1 mutation...
October 27, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29064543/effect-of-valproic-acid-administration-during-pregnancy-on-postnatal-development-of-cerebellar-cortex-and-the-possible-protective-role-of-folic-acid
#10
Saber I Shona, Ayman A Rizk, Abir O El Sadik, Hossam Y Emam, Eid N Ali
BACKGROUND: Valproic acid (VPA), one of the most important antiepileptic drugs (AEDs), is proved to be inevitable for epileptic pregnant women to limit the hazards of convulsions on the fetuses and mothers. Periconceptional folic acid supplementation was investigated to protect against several birth defects. However, its role against VPA cerebellar toxicity was not properly investigated. AIM: The present study was conducted to evaluate the protective effect of folic acid against VPA cerebellar neurotoxicity...
October 24, 2017: Folia Morphologica (Warsz)
https://www.readbyqxmd.com/read/29049976/sodium-valproate-enhances-doxorubicin-induced-cognitive-dysfunction-in-wistar-rats
#11
Thaneshwar Verma, Sanchari Basu Mallik, G V Ramalingayya, Pawan G Nayak, Anoop Kishore, K Sreedhara R Pai, Krishnadas Nandakumar
BACKGROUND: Increasing number of scientific reports have highlighted the role of histone acetylation/deacetylation in neurodegenerative conditions, including chemotherapy-induced cognitive dysfunction (also known as chemobrain). Multiple sources state that increased activity of histone deacetylases (HDACs) play a detrimental role in chemobrain. In the present study, sodium valproate, a well-known HDAC inhibitor, was explored for its neuroprotective potential against chemobrain development...
October 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28984330/an-unsymmetric-cisplatin-based-pt-iv-derivative-containing-2-2-propynyl-octanoate-a-very-efficient-multi-action-antitumor-prodrug-candidate
#12
Elisabetta Gabano, Mauro Ravera, Ilaria Zanellato, Stefano Tinello, Andrea Gallina, Beatrice Rangone, Valentina Gandin, Cristina Marzano, Maria Grazia Bottone, Domenico Osella
The design, synthesis, characterization and biological properties of a Pt(iv) complex containing the very active inhibitor of histone deacetylase (2-propynyl)octanoic acid, POA, as an axial ligand are reported here. The title complex, namely (OC-6-44)-acetatodiamminedichlorido(2-(2-propynyl)octanoato)platinum(iv), 1, containing POA in racemic or in enantiomeric forms, was one/two orders of magnitude more active than cisplatin, depending on the chemo-sensitivity of the cancer cell lines. Moreover, 1 exhibited similar or even better antiproliferative activity than (OC-6-33)-diamminedichloridobis(2-propylpentanoato)platinum(iv), 2, containing two molecules of the well-known histone deacetylase inhibitor 2-propylpentanoic (valproic) acid...
October 24, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28904569/serum-insulin-and-leptin-levels-in-children-with-epilepsy-on-valproate-associated-obesity
#13
Talha Rehman, Deepak Sachan, Anubhuti Chitkara
BACKGROUND: Weight gain is a common adverse effect of sodium valproic acid (VPA) in children with epilepsy. Several mechanisms of VPA-induced obesity have been suggested such as increased appetite, facultative thermogenesis, and elevated insulin and leptin levels. In this study, we aimed to investigate the role of Insulin and Leptin in the pathogenesis of weight gain caused by VPA. MATERIALS AND METHODS: Body mass index (BMI) was calculated, and serum insulin and leptin levels were measured in 45 consecutive patients and 45 controls...
April 2017: Journal of Pediatric Neurosciences
https://www.readbyqxmd.com/read/28763744/genetic-polymorphisms-and-valproic-acid-plasma-concentration-in-children-with-epilepsy-on-valproic-acid-monotherapy
#14
Shenghui Mei, Weixing Feng, Leting Zhu, Yazhen Yu, Weili Yang, Baoqin Gao, Xiaojuan Wu, Zhigang Zhao, Fang Fang
PURPOSE: The aim of the study is to evaluate the association between genetic polymorphisms and valproic acid (VPA) concentration to dose ratio in children with epilepsy on VPA monotherapy. METHODS: A total of 137 children, aged 3.5-18 years, (89 males and 48 females) with epilepsy on sustained-release VPA monotherapy were enrolled. Trough plasma concentrations of VPA at steady-state were measured using an AXSYM automatic immunity analyzer. The values were divided by body weight and total daily dose to calculate concentration to dose ratio of VPA (CDRV)...
October 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/28747841/onychomadesis-a-rare-adverse-effect-in-early-period-valproic-acid-therapy
#15
Serhat Güler, İlhan Işık, Akın İşcan
Valproic acid is an effective, frequently used anticonvulsant drug. Typical adverse effects include weight gain, hair loss, and nausea. Hyperpigmentation, onycholysis, and onychomadesis are nail changes that can be seen after valproic acid use. Changes occur at the distal and proximal portions of the nail bed in onycholysis and onychomadesis, respectively. Onychomadesis is a very rare disease of childhood with the exception of systemic and genetic diseases. Here, we present a child aged 23 months, the youngest and the earliest isolated patient with onychomadesis, which occurred after valproic acid treatment and worried the family but resolved spontaneously...
June 2017: Türk Pediatri Arşivi
https://www.readbyqxmd.com/read/28720877/role-of-the-histone-deacetylase-inhibitor-valproic-acid-in-high-fat-diet-induced-hypertension-via-inhibition-of-hdac1-angiotensin-ii-axis
#16
J Choi, S Park, T K Kwon, S I Sohn, K M Park, J I Kim
BACKGROUND: Obesity is known as an epidemic worldwide because of consumption of westernized high-fat diets and one of the major risk factors of hypertension. Histone deacetylases (HDACs) control gene expression by regulating histone/non-histone protein deacetylation. HDAC inhibitors exert anti-cancer and anti-inflammatory effects and play a protective role in cardiovascular diseases. In the present study, we tested the effect of an FDA-approved pan-HDAC inhibitor valproic acid (VPA) on high-fat diet (HFD)-induced hypertension in mice...
November 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28643994/the-impact-of-valproic-acid-treatment-on-weight-gain-in-pediatric-patients-with-epilepsy
#17
Pietro Ferrara, Antonio Gatto, Valeria Blasi, Federica DI Ruscio, Domenica Battaglia
BACKGROUND: Valproic acid (VPA) is an antiepileptic drug, used for focal and generalized seizure. VPA treatment resulted in significant weight gain but there are no systematic data about the prevalence of this side effect. The aim of the study is to evaluate the weight gain of a paediatric population with epilepsy. METHODS: We enrolled 38 patients, 17 female and 21 male with a mean age of 8.2±4.4 years. We evaluated data about height, weight and BMI at beginning of treatment and at 24, 36 and 48 months of follow-up...
June 22, 2017: Minerva Pediatrica
https://www.readbyqxmd.com/read/28626875/effect-of-ketogenic-diet-and-other-dietary-therapies-on-anti-epileptic-drug-concentrations-in-patients-with-epilepsy
#18
G Heo, S H Kim, M J Chang
WHAT IS KNOWN AND OBJECTIVE: The ketogenic diet (KD) is an effective high-fat, adequate-protein, low-carbohydrate diet for patients with refractory epilepsy. The aim of this study was to investigate the potential effects of the KD and other dietary therapies on the concentrations of anticonvulsants in patients with epilepsy. METHODS: Patients with epilepsy who were treated with the KD and other dietary therapies for more than 30 days with at least one measurement performed both before and during the diet were evaluated...
June 18, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28604475/analysis-of-the-variables-influencing-valproic-acid-concentration-in-the-serum-and-cerebrospinal-fluid-of-chinese-patients-after-craniotomy
#19
Zhihong Li, Weiqi Gao, Guifen Liu, Weihong Chen
BACKGROUND: Valproic acid (VPA) has been widely used in Chinese patients after craniotomy. Many studies have focused on the influencing factors of VPA serum concentration, but conclusions are sometimes paradoxical. Furthermore, the concentration of VPA in the cerebrospinal fluid (CSF) has been rarely reported. In the present study, VPA CSF concentrations were measured, and the potential factors influencing serum concentration and CSF distribution of VPA were investigated. In addition, the functional relationship between serum and CSF concentration was explored...
August 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28486989/postnatal-treatment-using-curcumin-supplements-to-amend-the-damage-in-vpa-induced-rodent-models-of-autism
#20
Maha Al-Askar, Ramesa Shafi Bhat, Manar Selim, Laila Al-Ayadhi, Afaf El-Ansary
BACKGROUND: Valproic acid (VPA) is used as a first-line antiepileptic agent and is undergoing clinical trials for use as a treatment for many disorders. Mothers undergoing VPA treatment during early pregnancy reportedly show increased rates of autism among their offspring. The benefits of curcumin supplementation were investigated using an animal model of VPA-induced autism. METHODS: The study was performed using a rodent model of autism by exposing rat fetuses to valproic acid (VPA) on the 12...
May 10, 2017: BMC Complementary and Alternative Medicine
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