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Aglaia Vignoli, Miriam Nella Savini, Maria Sonia Nowbut, Angela Peron, Katherine Turner, Francesca La Briola, Maria Paola Canevini
: Approximately 60-80% of girls with Rett Syndrome (RTT) have epilepsy, which represents one of the most severe problems clinicians have to deal with, especially when patients are 7-12years old. The aim of this study was to analyze the antiepileptic drugs (AEDs) prescribed in RTT, and to assess their effectiveness and tolerability in different age groups from early infancy to adulthood. We included in this study 104 girls, aged 2-42years (mean age 13.9years): 89 had a mutation in MECP2, 5 in CDKL5, 2 in FOXG1, and the mutational status was unknown in the remaining 8...
December 15, 2016: Epilepsy & Behavior: E&B
Haibin Jin, Xiaoming Guo
BACKGROUND: Viral myocarditis, which is often caused by coxsackievirus B3 (CVB3), is a serious clinical disorder characterized by excessive myocardial inflammation. Valproic acid (VPA) is described as a histone deacetylase inhibitor that has anti-inflammatory effects in several inflammatory diseases. However, the role and the detailed mechanism of VPA in viral myocarditis remain unclear. METHODS: Experimental CVB3-induced myocarditis was induced in mice by intraperitoneally (i...
October 10, 2016: Virology Journal
Sameer Hassamal, Susan Waller, Kimberly Reese, Claudia Testa
Valproic acid (VPA) is approved by the Food and Drug Administration (FDA) for the treatment of manic or mixed episodes associated with bipolar disorder. VPA is also used off-label to treat other conditions in psychiatry such as impulse control disorders, major depression, and posttraumatic stress disorder (PTSD). Although VPA is mostly well-tolerated, common adverse effects include gastrointestinal symptoms (nausea, vomiting, diarrhea), neurological symptoms (sedation, ataxia, tremor), weight gain, and alopecia...
2016: Türk Psikiyatri Dergisi, Turkish Journal of Psychiatry
Sareh Pandamooz, Mohammad Saied Salehi, Mohammad Nabiuni, Leila Dargahi
OBJECTIVE: Spinal cord injury (SCI) is a devastating condition causing neuronal loss. A key challenge in treatment of SCI is how to retain neurons after injury. Valproic acid (VPA) is a drug recently has been appreciated for its neuroprotective and neurotrophic properties in various SCI models. In this study the role of VPA was assessed in organotypic spinal cord slice culture following the contusion. DESIGN: The lumbar enlargement of adult rat was cut transversely and slices were cultured...
August 31, 2016: Journal of Spinal Cord Medicine
Jon B Stephenson, Melanie L Flater, Lisa T Bain
The Georgia Bureau of Investigation utilized a silylation method of analysis for low molecular weight carboxylic acids in the past. Due to the negative impact such derivatizations can have on gas chromatography-mass spectrometry (GC-MS) systems an alternative means of analysis was investigated. The described method is a whole blood solid phase extraction of valproic acid, salicylic acid and ibuprofen utilizing butylation for sensitivity and improved chromatography by GC-MS. The method produced a limit of detection and limit of quantitation at 1 mg/L for valproic acid, 2 mg/L for salicylic acid and 0...
October 2016: Journal of Analytical Toxicology
Ahmed M Kabel, Mohamed S Omar, Maaly A Abd Elmaaboud
Bleomycin is one of the anticancer agents used frequently in management of various types of tumors. Pulmonary fibrosis is the major limiting factor for the use of bleomycin. Mechanisms of fibrosis may include disordered wound healing, infiltration with inflammatory cells and fibroblasts and release of reactive oxygen species and growth factors. The aim of this study was to investigate the effect of valproic acid and butyrate on lung fibrosis induced by bleomycin, and to clarify their mechanisms of action. Fifty male Wistar rats were divided into 5 equal groups as follows: control group; bleomycin group; bleomycin+valproic acid group; bleomycin+butyrate group and bleomycin+valproic acid+butyrate group...
October 2016: International Immunopharmacology
Ji-Yun Huang, Yun Tian, Hui-Juan Wang, Hong Shen, Huan Wang, Sen Long, Mei-Hua Liao, Zhi-Rong Liu, Ze-Ming Wang, Dan Li, Rong-Rong Tao, Tian-Tian Cui, Shigeki Moriguchi, Kohji Fukunaga, Feng Han, Ying-Mei Lu
BACKGROUND: Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders that display complicated behavioral symptoms. METHODS: Using gene expressing profiling and the weighted gene co-expression network analysis (WGCNA), we studied genes coregulated by similar factors such as genetic variants or environmental effects in the hippocampus in an animal model of autism. RESULTS: From microarray data, we identified 21,388 robustly expressed genes of which 721 genes were found to be differently expressed in the valproic acid-treated group compared to the control group...
October 2016: CNS Neuroscience & Therapeutics
Sudhir Chandra Sarangi, Manjari Tripathi, Ashish Kumar Kakkar, Yogendra Kumar Gupta
BACKGROUND & OBJECTIVES: Certain antiepileptic drugs (AEDs) such as valproic acid (VPA) are known to affect body weight, and lipid profile. However, evidences regarding effects of AEDs on the body composition are deficient. This cross-sectional study compared the body composition and lipid profile among patients with epilepsy on newer and conventional AEDs. METHODS: The patients with epilepsy (n=109) on treatment with conventional and newer AEDs (levetiracetam, lamotrigine and clobazam) for > 6 months were enrolled...
March 2016: Indian Journal of Medical Research
Jelena Podgorac, Vesna Pešić, Željko Pavković, Ljiljana Martać, Selma Kanazir, Ljupka Filipović, Slobodan Sekulić
Clinical research has identified developmental delay and physical malformations in children prenatally exposed to the antiepileptic drug (AED) valproic acid (VPA). However, the early signs of neurodevelopmental deficits, their evolution during postnatal development and growth, and the dose effects of VPA are not well understood. The present study aimed to examine the influence of maternal exposure to a wide dose range (50, 100, 200 and 400mg/kg/day) of VPA during breeding and gestation on early physical and neuromotor development in mice offspring...
September 15, 2016: Behavioural Brain Research
Renin Chang, Mei-Chia Chou, Li-Ying Hung, Mu-En Wang, Meng-Chieh Hsu, Chih-Hsien Chiu
Valproic acid (VPA) is one of the most widely used antiepilepsy drugs. However, several side effects, including weight gain and fatty liver, have been reported in patients following VPA treatment. In this study, we explored the molecular mechanisms of VPA-induced hepatic steatosis using FL83B cell line-based in vitro model. Using fluorescent lipid staining technique, we found that VPA enhanced oleic acid- (OLA-) induced lipid accumulation in a dose-dependent manner in hepatocytes; this may be due to upregulated lipid uptake, triacylglycerol (TAG) synthesis, and lipid droplet formation...
2016: BioMed Research International
Tomoya Takeuchi, Jun Natsume, Hiroyuki Kidokoro, Naoko Ishihara, Hiroyuki Yamamoto, Yoshiteru Azuma, Yuji Ito, Naoko Kurahashi, Takeshi Tsuji, Motomasa Suzuki, Kazuya Itomi, Keitaro Yamada, Hirokazu Kurahashi, Shinpei Abe, Akihisa Okumura, Koichi Maruyama, Tamiko Negoro, Kazuyoshi Watanabe, Seiji Kojima
PURPOSE: Although it has been reported that some antiepileptic drugs have inducing or inhibiting effects on lamotrigine (LTG) clearance, whether they have the same effects in Asian epilepsy patients as in those in other countries has not been clarified, especially in children. The aim of this study was to determine the effects of co-medications on LTG clearance in Japanese children with epilepsy. METHODS: A total of 342 routine serum concentration measurements of LTG in 102 Japanese epilepsy patients under 20years of age were reviewed...
September 2016: Brain & Development
Ravindra Arya, Catherine W Gillespie, Avital Cnaan, Mahima Devarajan, Peggy Clark, Shlomo Shinnar, Alexander A Vinks, Kana Mizuno, Tracy A Glauser
OBJECTIVE: This study examined whether overweight and obesity are pretreatment comorbidities and predictors of short-term drug response in newly diagnosed untreated childhood absence epilepsy (CAE). We also examined whether dietary intake accounts for observed pretreatment body mass index (BMI) distribution. METHODS: Pretreatment height and weight were available for 445 of 446 participants in the NIH-funded CAE comparative effectiveness trial (NCT00088452). Twenty-four-hour dietary recalls were collected...
April 26, 2016: Neurology
Linda Bingsohn, Eileen Knorr, Andreas Vilcinskas
Pharmaceuticals are not currently tested for transgenerational and epigenetic side effects. The use of vertebrates as preclinical research models is limited by their long generation times, low numbers of progeny and ethical concerns. In contrast, invertebrates such as insects breed rapidly, produce many offspring and are more ethically acceptable, allowing them to be used for high-throughput screening. Here, we established Tribolium castaneum as a model to screen for the effect of drugs on complex fitness parameters and the expression of epigenetic regulatory genes...
July 2016: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
Eun-Kee Bae, Jongtae Lee, Jung-Won Shin, Jangsup Moon, Keon-Joo Lee, Yong-Won Shin, Tae-Joon Kim, Dongseong Shin, In-Jin Jang, Sang Kun Lee
PURPOSE: To identify the factors influencing topiramate pharmacokinetics (PK) in a large population of adult patients with epilepsy using population PK analysis. METHODS: Clinical data and blood samples were collected from 550 adult patients with epilepsy treated using topiramate. Nonlinear mixed effects modeling software (NONMEM, version 7.2) was used to fit the plasma concentration to a one-compartment PK model. Demographic and clinical variables tested as potential covariates were age, sex, body weight, height, serum creatinine, creatinine clearance (CLcr), total bilirubin, prothrombin time, albumin, aspartate transaminase (AST), alanine transaminase (ALT), daily dose (DOSE), and concomitant medications (phenytoin [PHT], clobazam, carbamazepine [CBZ], valproic acid, lamotrigine, levetiracetam, oxcarbazepine [OXC], pregabalin, clonazepam, and phenobarbital [PB])...
April 2016: Seizure: the Journal of the British Epilepsy Association
Alexis Arzimanoglou, Jose A Ferreira, Andrew Satlin, Shannon Mendes, Betsy Williams, David Critchley, Edgar Schuck, Ziad Hussein, Dinesh Kumar, Shobha Dhadda, Francesco Bibbiani
OBJECTIVE: A good knowledge of safety and age group-specific pharmacokinetics (PK) of antiepileptic drugs (AEDs) in young pediatric patients is of great importance in clinical practice. This paper presents 6-month interim safety and PK from an ongoing 2-year open-label study (Study 303) of adjunctive rufinamide treatment in pediatric subjects ≥ 1 to < 4 years with inadequately controlled epilepsies of the Lennox-Gastaut syndrome (LGS) spectrum. METHODS: Subjects (N = 37) were randomized to either rufinamide or any other approved AED chosen by the investigator as adjunctive therapy to the subject's existing regimen of 1-3 AEDs...
May 2016: European Journal of Paediatric Neurology: EJPN
Kazuyuki Inoue, Yoshiaki Yamamoto, Eri Suzuki, Toshiki Takahashi, Akiko Umemura, Yukitoshi Takahashi, Katsumi Imai, Yushi Inoue, Keita Hirai, Daiki Tsuji, Kunihiko Itoh
PURPOSE: Lamotrigine (LTG) is used to treat epilepsy. The variability of LTG pharmacokinetics among individuals may be attributed to polymorphisms in the genes of uridine diphosphate glucuronosyltransferases (UGTs) 1A4 and UGT2B7 and/or combination with other drugs. In this study, we evaluated the association between LTG concentrations and patient characteristics such as genetic polymorphisms and the co-administration of antiepileptic drugs. METHODS: We recruited 122 patients with epilepsy...
May 2016: European Journal of Clinical Pharmacology
Ivana Kacirova, Milan Grundmann, Hana Brozmanova
AIMS: The data on the valproic acid transplacental transfer and risk to the fetus of exposure, remain sparse and only a limited number of studies have reported umbilical cord blood levels. MATERIALS AND METHODS: Maternal and umbilical cord serum levels were analyzed at delivery in a cohort of 58 women, between the years 1991 - 2013. The request forms for routine therapeutic drug monitoring were used as the data source. Maternal levels and dosing information were used for estimating the maternal apparent oral clearance and the paired umbilical cord and maternal levels for estimation of umbilical cord/maternal level ratios...
December 2015: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
K Ikeda, C Ueda, K Yamada, A Nakamura, Y Hatsuda, S Kawanishi, S Nishii, M Ogawa
Human choriocarcinoma has been used as a model to study trophoblast transcellular drug transport in the placenta. Previous models had limitations regarding low molecular weight drug transport through the intracellular gap junction. The purpose of this study was to evaluate placental carrier-mediated transport across a differentiating JEG-3 choriocarcinoma cell (DJEGs) layer model in which the intracellular gap junction was restricted. Cimetidine is the substrate of an efflux transporter, breast cancer resistance protein (BCRP)...
July 2015: Die Pharmazie
C R Carmona-Vazquez, M Ruiz-Garcia, D M Pena-Landin, L Diaz-Garcia, S R Greenawalt
INTRODUCTION: Valproic acid (VPA) is a useful antiepileptic drug for controlling different types of epilepsy. It has several side effects and is associated to increased body weight, as well as metabolic and endocrine disorders, including metabolic syndrome. AIM: To determine the prevalence of obesity and metabolic syndrome among paediatric patients with epilepsy treated in monotherapy with VPA. PATIENTS AND METHODS: The study was cross-sectional, observational and analytical...
September 1, 2015: Revista de Neurologia
M Noai, H Soraoka, A Kajiwara, Y Tanamachi, K Oniki, K Nakagawa, T Ishitsu, J Saruwatari
OBJECTIVES: Cytochrome P450 (CYP) 2C19 plays a role in the biotransformation of clinically relevant drugs as well as endogenous compounds, including sex hormones, which are known to be modulators of food intake and energy balance in humans. We attempted to investigate the influence of CYP2C19 polymorphisms on valproic acid (VPA)-induced weight gain. MATERIALS AND METHODS: This retrospective longitudinal study included 85 VPA-treated and 93 carbamazepine (CBZ)-treated (as a reference) young patients with epilepsy...
March 2016: Acta Neurologica Scandinavica
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