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Dana Jazayeri, Janet Graham, Alison Hitchcock, Terence J O'Brien, Frank J E Vajda
PURPOSE: Antiepileptic drugs (AEDs), particularly valproate (VPA), are known to be teratogens when taken by women with epilepsy (WWE), but the risk in women who take these drugs for indications other than epilepsy have been little studied. This study aims to investigate the incidence of birth defects in children born to mothers taking AEDs for non-epilepsy indications. METHODS: The Australian Pregnancy Register (APR), established in 1998, is a prospective observational study operating with ethical approval and informed written consent for participation...
February 17, 2018: Seizure: the Journal of the British Epilepsy Association
Zahre Sajadpoor, Zeinab Amini-Farsani, Hossein Teimori, Mehdi Shamsara, Mohammad Hossein Sangtarash, Payam Ghasemi-Dehkordi, Farrokh Yadollahi
Cisplatin resistance is one of the main limitations in the treatment of ovarian cancer, which is partly mediated by long noncoding RNAs (lncRNAs). H19 is a lncRNA involving in cisplatin resistance in cancers. Valproic acid (VPA) is a commonly used drug for clinical treatment of seizure disorders. In addition, this drug may display its effects through regulation of noncoding RNAs controlling gene expression. The aim of the present study was the investigation of VPA treatment effect on H19 expression in ovarian cancer cells and also the relation of the H19 levels with apoptosis and cisplatin resistance...
February 22, 2018: Applied Biochemistry and Biotechnology
Varun Monga, Umang Swami, Munir Tanas, Aaron Bossler, Sarah L Mott, Brian J Smith, Mohammed Milhem
Epigenetic events and genetic alterations under the control of the tumor microenvironment potentially mediate tumor induced angiogenesis involved in soft tissue sarcoma (STS) metastasis. Addition of antiangiogenic agent, such as bevacizumab, to standard chemotherapy in treatment of sarcoma has been studied in clinical trials, but most of the findings have not supported its use. We hypothesized the existence of an epigenetically mediated "angiogenic switch", and the tumor microenvironment, prevents bevacizumab from truly blocking angiogenesis...
February 17, 2018: Cancers
Daniela Kühn, Martin Ptok, Michael Jungheim
OBJECTIVE: In about one-third of brass instrumentalists, there are stress-related insufficiencies of velopharyngeal closure (VPC), i. e. the intraoral pressure exceeds the barrier formed by the VPC. Here, it was the aim to measure the VPC closing pressure while playing a trumpet and to evaluate the influence of a 30 minute stress sequence on the muscular activities in the VPC. MATERIAL AND METHODS: Sample: 6 healthy volunteers; task: to play the sound h1 for 5 seconds with 85 dB(A) and with 100 dB(A)...
February 20, 2018: Laryngo- Rhino- Otologie
Wenjin Xi, Xu Chen, Jinbo Sun, Wei Wang, Yi Huo, Guoxu Zheng, Jieheng Wu, Yufang Li, Angang Yang, Tao Wang
BACKGROUND Histone acetylation and DNA methylation are important mammalian epigenetic modifications that participate in the regulation of gene expression. Because dysregulation of histone deacetylase and DNA methyltransferases are hallmarks of malignancy, they have become promising therapeutic targets. In this study, we explored the anti-tumor activity of valproic acid (VPA), a histone deacetylase inhibitor (HDACi) and 5-Aza-2'-deoxycytidine (5-Aza), an inhibitor of DNA methyltransferases, on renal cell carcinoma (RCC) cell lines 786-O and 769-P...
February 19, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Eiji Yamato
OBJECTIVE: Histone deacytylase inhibitors (HDACis) inhibit the deacetylation of the lysine residue of proteins, including histones, and regulate the transcription of a variety of genes. Recently, HDACis have been used clinically as anti-cancer drugs and possible anti-diabetic drugs. Even though HDACis have been proven to protect the cytokine-induced damage of pancreatic beta cells, evidence also shows that high doses of HDACis are cytotoxic. In the present study, we, therefore, investigated the eff ect of HDACis on insulin secretion in a pancreatic beta cell line...
January 1, 2018: Endocrine Regulations
Cecilie Johannessen Landmark, Anette Huuse Farmen, Margrete Larsen Burns, Arton Baftiu, Morten I Lossius, Svein I Johannessen, Torbjörn Tomson
BACKGROUND AND PURPOSE: Use of valproate (VPA) in women of childbearing age is restricted due to dose-dependent risk of teratogenicity. The purpose of this study was to characterise pharmacokinetic variability of VPA in pregnancy, and discuss use of therapeutic drug monitoring (TDM) as guidance to exposure in women. METHOD: Measurements of trough total and unbound VPA concentrations before, during and after pregnancy, at assumed steady-state were collected from the TDM-database (2006-2016) at the National Center for Epilepsy in Norway...
February 11, 2018: Epilepsy Research
Mini Sreedharan, Kalpana Devadathan, Kunju P A Mohammed, Bindusha Sasidharan, Jayakumar Parameswaran Pillai, Minikumari Amma Vasumathy Amma, Saboorabeegum Muthubeevi
OBJECTIVE: To assess the effect of monotherapy with Carbamazepine (CBZ) and Sodium valproate (VPA) on serum 25-OH Vitamin D levels in children with epilepsy compared to controls. DESIGN: Cross-sectional study. SETTING: Outpatient department of a tertiary-care Pediatric Neurology centre, and a nearby day-care centre and school. STUDY PERIOD: June 2012 to May 2013. PARTICIPANTS: Children with epilepsy aged 2 to 13 years on monotherapy with CBZ (n=28) or VPA (n=28) for at least 6 months; 109 age-matched controls from a nearby day-care centre and school...
February 9, 2018: Indian Pediatrics
Ruoxin Zhang, Jinlong Zhou, Junrong Ren, Siqi Sun, Yuanyuan Di, Hanyu Wang, Xiaoqin An, Kexin Zhang, Junfeng Zhang, Zhaoqiang Qian, Meimei Shi, Yanning Qiao, Wei Ren, Yingfang Tian
Gene-environmental interaction could be the major cause of autism. The aim of the current study is to detect the effects of valproic acid on gene expression profiles and alternatively spliced genes in the prefrontal cortex in rat models of autism. Female rats received a single intraperitoneal injection of 600 mg/kg valproic acid at day 12.5 post-conception, and controls were injected with saline. Only male offspring were employed in the current study. RNA sequencing was used to investigate transcriptome in the prefrontal cortex of VPA-exposed rats...
February 7, 2018: Reproductive Toxicology
Jie Zhang, Juraj Balkovič, Ligia B Azevedo, Rastislav Skalský, Alexander F Bouwman, Guang Xu, Jinzhou Wang, Minggang Xu, Chaoqing Yu
This study analyzes the influence of various fertilizer management practices on crop yield and soil organic carbon (SOC) based on the long-term field observations and modelling. Data covering 11 years from 8 long-term field trials were included, representing a range of typical soil, climate, and agro-ecosystems in China. The process-based model EPIC (Environmental Policy Integrated Climate model) was used to simulate the response of crop yield and SOC to various fertilization regimes. The results showed that the yield and SOC under additional manure application treatment were the highest while the yield under control treatment was the lowest (30%-50% of NPK yield) at all sites...
January 29, 2018: Science of the Total Environment
Frederick Kofi Korley, Vahagn C Nikolian, Aaron M Williams, Isabel S Dennahy, Michael Weykamp, Hasan B Alam
The primary aim of this study was to examine the effects of valproic acid (VPA) treatment on serum glial fibrillary acidic protein (GFAP) and neurofilament light chain (NF-L) levels. To achieve this aim, we obtained serum samples from: (1) ten Yorkshire swine subjected to controlled cortical impact (CCI) TBI + polytrauma and randomized to receive either normal saline (NS) + VPA (n=5) or NS alone (n=5) and (2) five additional swine subjected to CCI TBI without polytrauma and treated with VPA. GFAP and NF-L levels were measured in samples obtained from baseline until 10 days post-injury using a digital immunoassay from Quanterix Corporation...
February 7, 2018: Journal of Neurotrauma
Brittany D Needham, Weiyi Tang, Wei-Li Wu
Social impairment is one of the major symptoms in multiple psychiatric disorders, including autism spectrum disorder (ASD). Accumulated studies indicate a crucial role for the gut microbiota in social development, but these mechanisms remain unclear. This review focuses on two strategies adopted to elucidate the complicated relationship between gut bacteria and host social behavior. In a top-down approach, researchers have attempted to correlate behavioral abnormalities with altered gut microbial profiles in rodent models of ASD, including BTBR mice, maternal immune activation (MIA), maternal valproic acid (VPA) and maternal high-fat diet (MHFD) offspring...
February 7, 2018: Developmental Neurobiology
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
Panpan Chang, Michael Weykamp, Isabel S Dennahy, Aaron M Williams, Umar F Bhatti, Baoling Liu, Vahagn C Nikolian, Yongqing Li, Hasan B Alam
BACKGROUND: Hemorrhage is a leading preventable cause of death. Non-selective histone deacetylase inhibitors (HDACIs), such as valproic acid (VPA), have been shown to improve outcomes in hemorrhagic shock (HS). HDACs can be divided into 4 functional classes (I, IIa/IIb, III & IV). Classes I, IIa/IIb, and III have previously been implicated in the pathophysiology of HS. This study aimed to determine which HDAC class, or classes, are responsible for the survival benefit observed with non-selective HDACIs...
February 3, 2018: Journal of Trauma and Acute Care Surgery
Hamizah Mohd Yunos, Andrew Green
INTRODUCTION: Fetal valproate syndrome was first described in 1984. Valproic acid crosses the placenta and can potentially lead to major congenital malformation, dysmorphism and neurodevelopmental disorder. METHODS: A retrospective study of 29 cases of FVS diagnosed by geneticists from 1995 to 2016. The cases were diagnosed based on criteria of fetal anticonvulsant syndrome. RESULTS: A total of 29 cases reported in the last 21 years. Features commonly described are prominent metopic ridge, midface hypoplasia, epicanthic folds, micrognathia and broad and flat nasal bridge...
February 3, 2018: Irish Journal of Medical Science
Kazuyasu Fujii, Norihiro Suzuki, Nozomi Jimura, Masashi Idogawa, Tadashi Kondo, Keiji Iwatsuki, Takuro Kanekura
BACKGROUND: The anticancer effects of histone deacetylase inhibitors (HDACi) vary between patients, and their molecular mechanisms remain poorly understood. Previously, we have identified heat shock 70 kDa protein 1A (HSPA1A, also known as HSP72) as the most overexpressed protein in valproic acid (VPA)-resistant cell lines. KNK437, an inhibitor of heat shock proteins, enhanced the cytotoxic effects of not only VPA but also vorinostat, another HDACi. However, the mechanisms underlying the role of HSP72 in resistance against HDACi remain largely unknown...
January 30, 2018: Journal of Dermatological Science
Zhong-Fang He, Jun Chen, Chao-Ning Zhou, Zhi Rao, Xiao-Hua Wang
RATIONALE: Sodium valproate (VPA) and lamotrigine (LTG) are widely used antiepileptic drugs, disabling postural, and action tremors after using LTG with VPA were reported in 1993. However, in this study, we describe a patient in whom disabling resting-type tremor induced by 2-year use of VPA and LTG. PATIENT CONCERNS: A 50-year old man was referred to department of neurology because of involuntary upper limbs resting-type tremor with high amplitude that had begun 6 months previously and progressively worsened, and he could not work on the day of visit...
November 2017: Medicine (Baltimore)
Miyuki Yasue, Akiko Nakagami, Keiko Nakagaki, Noritaka Ichinohe, Nobuyuki Kawai
Humans and various nonhuman primates respond negatively to inequity not in their favor (i.e., inequity aversion), when inequity between two individuals is introduced. Common marmosets, a highly prosocial species, further discriminated between human actors who reciprocated in social exchanges, and those who did not. Conversely, marmoset models of autism, induced via prenatal exposure to valproic acid (VPA marmosets), did not discriminate. Interestingly, previous studies of inequity aversion in marmosets have produced negative results, or were limited to males...
January 24, 2018: Behavioural Brain Research
Lauren D Grünspan, Ben Hur M Mussulini, Suelen Baggio, Paulo R Dos Santos, Françoise Dumas, Eduardo P Rico, Diogo L de Oliveira, Sidnei Moura
Valproic acid (VPA) is an antiepileptic drug (AED) that has the broadest spectrum across all types of seizures and epileptic syndromes. Unfortunately, approximately 30% of epileptic patients are refractory to the classical AED. Metal ions have been frequently incorporated into pharmaceuticals for therapeutic or diagnostic purposes and research. In this preliminary study, we assess the embryo toxicity and the anticonvulsant activity of 4 novel metallodrugs, with Zn+2 and Cu+2, a derivative of valproic acid and the N-donor ligand in an adult zebrafish epileptic seizure model induced by pentylenetetrazole...
January 19, 2018: Epilepsy Research
Cameron S Metcalf, Brian D Klein, Misty D Smith, Marc Ceusters, Hilde Lavreysen, Stefan Pype, Nancy Van Osselaer, Roy Twyman, H Steve White
OBJECTIVE: We previously demonstrated that positive allosteric modulators (PAMs) of metabotropic glutamate subtype 2 (mGlu2 ) receptors have potential synergistic interactions with the antiseizure drug levetiracetam (LEV). The present study utilizes isobolographic analysis to evaluate the combined administration of JNJ-46356479, a selective and potent mGlu2 PAM, with LEV as well as sodium valproate (VPA) and lamotrigine (LTG). METHODS: The anticonvulsant efficacy of JNJ-46356479 was evaluated in the 6-Hz model of psychomotor seizures in mice...
January 23, 2018: Epilepsia
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