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Komariah Komariah, Wasmen Manalu, Bambang Kiranadi, Adi Winarto, Ekowati Handharyani, M Orliando Roeslan
Valproic acid (VPA) plays a role in histone modifications that eventually inhibit the activity of histone deacetylase (HDAC), and will affect the expressions of genes Pdx1, Nkx6.1, and Ngn3 during pancreatic organogenesis. This experiment was designed to study the effect of VPA exposure in pregnant rats on the activity of HDAC that controls the expression of genes regulating the development of beta cells in the pancreas to synthesize and secrete insulin. This study used 30 pregnant Sprague-Dawley rats, divided into 4 groups, as follows: (1) a control group of pregnant rats without VPA administration, (2) pregnant rats administered with 250 mg VPA on day 10 of pregnancy, (3) pregnant rats administered with 250 mg VPA on day 13 of pregnancy, and (4) pregnant rats administered with 250 mg VPA on day 16 of pregnancy...
April 2018: Toxicological Research
Weixing Feng, Shenghui Mei, Leting Zhu, Yazhen Yu, Weili Yang, Baoqin Gao, Xiaojuan Wu, Zhigang Zhao, Fang Fang
PURPOSE: This study aims to evaluate the associations between genetic polymorphisms and the effect of sodium valproate (VPA) therapy in children with generalized seizures. METHODS: A total of 174 children with generalized seizures on VPA therapy were enrolled. Steady-state trough plasma concentrations of VPA were analyzed. Seventy-six single nucleotide polymorphisms involved in the absorption, metabolism, transport, and target receptor of VPA were identified, and their associations with the therapeutic effect (seizure reduction) were evaluated using logistic regression adjusted by various influence factors...
April 14, 2018: Seizure: the Journal of the British Epilepsy Association
Nafiye Polat Çiçek, Tülay Kamaşak, Mine Serin, Aysenur Okten, Ahmet Alver, Ali Cansu
PURPOSE: Although some drugs used in the treatment of epilepsy are known to affect body weight, the hormonal factors responsible have not been sufficiently described. The purpose of this study was to compare insulin, leptin, neuropeptide Y and ghrelin levels in children with epilepsy receiving monotherapy with topiramate (TPM) and valproic acid (VPA), the drugs whose effects on body weight have been most discussed, with those of a control group. METHOD: 48 patients (25 VPA, 23 TPM) aged between 6 and 15...
April 11, 2018: Seizure: the Journal of the British Epilepsy Association
Miriam Rubinchik-Stern, Miriam Shmuel, Jacob Bar, Michal Kovo, Sara Eyal
OBJECTIVE: In utero exposure to valproic acid (VPA) has been associated with worse pregnancy outcomes compared to all other antiepileptic drugs. We have previously shown that VPA alters the expression of placental transporters for hormones and nutrients in vitro and in pregnant mice. Here, our aim was to characterize the effects of short exposure to VPA on the expression of carriers for compounds essential for fetal development in human placentas ex vivo, under controlled conditions...
April 17, 2018: Epilepsia
Shenghui Mei, Weixing Feng, Leting Zhu, Xingang Li, Yazhen Yu, Weili Yang, Baoqin Gao, Xiaojuan Wu, Fang Fang, Zhigang Zhao
PURPOSE: Valproic acid (VPA) is an important drug in seizure control with great inter-individual differences in metabolism and treatment effect. This study aims to identify the effects of genetic variants on VPA clearance in a population pharmacokinetic (popPK) model in children with epilepsy. METHODS: A total of 325 VPA plasma concentrations from 290 children with epilepsy were used to develop the popPK model by using the nonlinear mixed-effects modeling method...
April 17, 2018: European Journal of Clinical Pharmacology
Muyun Wei, Shaowei Mao, Guoliang Lu, Liang Li, Xiaopeng Lan, Zhongxian Huang, Yougen Chen, Miaoqing Zhao, Yueran Zhao, Qinghua Xia
BACKGROUND: Metformin (Met) is a widely available diabetic drug and shows suppressed effects on renal cell carcinoma (RCC) metabolism and proliferation. Laboratory studies in RCC suggested that metformin has remarkable antitumor activities and seems to be a potential antitumor drug. But the facts that metformin may be not effective in reducing the risk of RCC in cancer clinical trials made it difficult to determine the benefits of metformin in RCC prevention and treatment. The mechanisms underlying the different conclusions between laboratory experiments and clinical analysis remains unclear...
April 17, 2018: BMC Cancer
Sheng-Yu Lee, Tzu-Yun Wang, Shiou-Lan Chen, Yun-Hsuan Chang, Po-See Chen, San-Yuan Huang, Nian-Sheng Tzeng, Liang-Jen Wang, I Hui Lee, Kao Ching Chen, Yen Kuang Yang, Jau-Shyong Hong, Ru-Band Lu
BACKGROUND: Bipolar disorder (BD), especially BD-II, is frequently comorbid with alcohol dependence. Because BD-II and alcohol dependence are neurodegenerative disorders, agents with anti-inflammatory and neurotrophic effects might provide effective therapy. We investigated whether add-on memantine to regular valproate (VPA) treatment ameliorated clinical symptoms, reduced alcohol use and cytokine levels, and increased plasma brain-derived neurotrophic factor (BDNF) in BD-II patients with comorbid alcohol dependence...
April 15, 2018: Alcoholism, Clinical and Experimental Research
Paola Sgadò, Orsola Rosa-Salva, Elisabetta Versace, Giorgio Vallortigara
Biological predispositions to attend to visual cues, such as those associated with face-like stimuli or with biological motion, guide social behavior from the first moments of life and have been documented in human neonates, infant monkeys and domestic chicks. Impairments of social predispositions have been recently reported in neonates at high familial risk of Autism Spectrum Disorder (ASD). Using embryonic exposure to valproic acid (VPA), an anticonvulsant associated to increased risk of developing ASD, we modeled ASD behavioral deficits in domestic chicks...
April 12, 2018: Scientific Reports
Li Qiliang, Song Wenqi, Jin Hong
OBJECTIVE: To explore the incidence and independent risk-factors of secondary carnitine deficiency in Chinese children with epilepsy on valproate monotherapy. METHODS: The free carnitine and acylcarnitines levels in 299 children with epilepsy on valproate monotherapy between June 2014 and September 2015 were compared with age- and sex-matched 299 healthy controls. RESULTS: Children with valproate monotherapy had lower free carnitine levels [23...
March 15, 2018: Indian Pediatrics
Fabio Carletti, Valerio Rizzo, Giuditta Gambino, Viviana De Caro, Flavia Maria Sutera, Libero Italo Giannola, Giuseppe Ferraro, Pierangelo Sardo
BACKGROUND: Research about improvement of epilepsy therapy is constantly growing. Valproyl-L-Phenylalanine (VPA-Phen) and N-valproyl-L-tryptophan (VPA-Tryp) were synthesized to increase the antiepileptic valproic acid efficacy. METHODS: VPA-Phen and VPA-Tryp were comparatively tested on CA1 hippocampal epileptiform bursting activity obtained by increasing potassium and lowering calcium and magnesium concentrations in the fluid perfusing rat brain slices. Each slice was treated with a single concentration (0...
April 8, 2018: Current Pharmaceutical Design
Gillian McLellan, Rosie Arthur, Duncan S Buchan
The GT3X+ worn at the wrist promotes greater compliance than at the hip. Minutes in SB and PA calculated from raw accelerations at the hip and wrist provide contrasting estimates and cannot be directly compared. Wear-time for the wrist (15.6 to 17.4 h.d-1 ) was greater than the hip (15.2 to 16.8 h.d-1 ) across several wear-time criteria (all P < 0.05). Moderate-strong associations were found between time spent in SB (r = 0.39), LPA (r = 0.33), MPA (r = 0.99), VPA (r = 0.82) and MVPA (r = 0...
April 5, 2018: Journal of Sports Sciences
Atsuhiko Sakai, Taito Matsuda, Hiroyoshi Doi, Yukiko Nagaishi, Kiyoko Kato, Kinichi Nakashima
Epilepsy is a neurological disorder often associated with seizure that affects ∼0.7% of pregnant women. During pregnancy, most epileptic patients are prescribed antiepileptic drugs (AEDs) such as valproic acid (VPA) to control seizure activity. Here, we show that prenatal exposure to VPA in mice increases seizure susceptibility in adult offspring through mislocalization of newborn neurons in the hippocampus. We confirmed that neurons newly generated from neural stem/progenitor cells (NS/PCs) are integrated into the granular cell layer in the adult hippocampus; however, prenatal VPA treatment altered the expression in NS/PCs of genes associated with cell migration, including CXC motif chemokine receptor 4 ( Cxcr4 ), consequently increasing the ectopic localization of newborn neurons in the hilus...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
Donatella Marazziti, Lionella Palego, Laura Betti, Gino Giannaccini, Enrico Massimetti, Stefano Baroni, Antonio Ciapparelli, Antonio Lucacchini, Federico Mucci, Liliana Dell'Osso
BACKGROUND: The aim of the present study was to appraise retrospectively the influence of valproate (VPA) and antidepressants (ADs) on the steady-state plasma concentrations of clozapine (CLZ), the prototype of various second-generation antipsychotics (SGAs), norclozapine (NCLZ, its main metabolite), and their ratio (NCLZ/CLZ). METHODS: Sixty-seven psychotic patients with a prevalent diagnosis of bipolar disorder (BD) were studied. We then analyzed data altogether and subdivided them into four groups, according to pharmacological treatments: #1 CLZ (n=21), #2 CLZ plus antidepressants (ADs) (n=13), #3 CLZ plus VPA (n=16), and #4 CLZ plus ADs plus VPA (n=17)...
March 29, 2018: Therapeutic Drug Monitoring
Maggie M Ramzy, Hend M Abdelghany, Nagwa M Zenhom, Nashwa F El-Tahawy
Liver fibrosis is an excessively reversible wound healing process and the fibrotic disorder is the activation of hepatic stellate cell that requires extensive alterations in gene expression. As reversible deacetylation of histone proteins modulate gene expression, we examined the effect of valproic acid (VPA) as selective histone deacetylase inhibitor on CCl-4 induced liver fibrosis. Thirty rats were divided into three equal groups; control group, fibrotic group and VPA-treated group. The rats were sacrificed after 6 weeks of liver fibrosis induction...
March 30, 2018: IUBMB Life
Marije J Veenstra, Peter M van Koetsveld, Fadime Dogan, William E Farrell, Richard A Feelders, Steven W J Lamberts, Wouter W de Herder, Giovanni Vitale, Leo J Hofland
Somatostatin receptors are a pivotal target for treatment of pancreatic neuroendocrine tumors (pNET), either with somatostatin analogues (SSA) or radiolabeled SSA. The highest affinity target for the most commonly used SSA is the somatostatin receptor type 2 ( sst 2 ). An important factor that may complicate treatment efficacy, is the variable number of receptors expressed on pNETs. Gene expression is subject to complex regulation, in which epigenetics has a central role. In this study we explored the possible role of epigenetic modifications in the variations in sst 2 expression levels in two human pNET cell lines, BON-1 and QGP-1...
March 13, 2018: Oncotarget
Haiyang Liu, Jia Li, Yan Zhao, Kexin Xie, Xianjin Tang, Shaoxian Wang, Zhongpei Li, Yulin Liao, Jianming Xu, Hongjie Di, Yong Li
Nitrification plays an important role in the soil nitrogen (N) cycle, and fertilizer application may influence soil nitrifiers' abundance and composition. However, the effect of long-term manure application in paddy soils on nitrifying populations is poorly understood. We chose four long-term manure experimental fields in the south of China to study how the abundance and community structure of nitrifiers would change in response to long-term manure application using quantitative PCR and Miseq sequencing analyses...
March 26, 2018: Science of the Total Environment
Hui He, Wen Li, Min Peng, Jianbing Qin, Jinhong Shi, Haoming Li, Meiling Tian, Xinhua Zhang, Guangming Lv, Guohua Jin
Neural stem cells (NSCs) possess self-renewal and multilineage differentiation ability, thus are considered to be a potential source for cell replacement therapy of many nervous system diseases, such as neurodegenerative diseases. Valproate (VPA), a member of histone deacetylase inhibitor family, is an epigenetic regulator and can promote NSCs to differentiate into neurons, nevertheless, the underlying mechanisms of the process remain unclear. MicroRNAs (miRNAs) exert a crucial part in the posttranscriptional regulation of gene expression...
March 25, 2018: Journal of Cellular Biochemistry
Emili Leary, Raj D Sheth, Barry E Gidal
PURPOSE: Conversion to lamotrigine (LTG) monotherapy from sodium valproate (VPA) is complicated by the robust pharmacokinetic interaction between the two AEDs. This study examined changes in LTG serum concentrations immediately following VPA discontinuation. METHODS: Ten healthy female and male adult subjects were initiated on LTG (Lamictal) 10 mg orally every morning for 30 days and VPA (Depakote ER) 500 mg orally every morning for 14 days. Morning trough (pre-dose) venous blood samples were obtained for determination of LTG and VPA concentrations on study days 14, 15, 16, 18, 20, 22, 24, 26, 28, and 30...
March 7, 2018: Seizure: the Journal of the British Epilepsy Association
Octavia Ramayanti, Mitch Brinkkemper, Sandra A W M Verkuijlen, Leni Ritmaleni, Mei Lin Go, Jaap M Middeldorp
Epstein-Barr virus (EBV) persists in nasopharyngeal (NPC) and gastric carcinomas (EBVaGC) in a tightly latent form. Cytolytic virus activation (CLVA) therapy employs gemcitabine and valproic acid (GCb+VPA) to reactivate latent EBV into the lytic phase and antiviral valganciclovir to enhance cell death and prevent virus production. CLVA treatment has proven safe in phase-I/II trials with promising clinical responses in patients with recurrent NPC. However, a major challenge is to maximize EBV lytic reactivation by CLVA...
March 22, 2018: Cancers
Christelle Rodrigues, Stéphanie Chhun, Catherine Chiron, Olivier Dulac, Elisabeth Rey, Gérard Pons, Vincent Jullien
PURPOSE: The objective of this work was to develop a population pharmacokinetic model for a prolonged-release granule formulation of valproic acid (VPA) in children with epilepsy and to determine the doses providing a VPA trough concentration (Ctrough ) within the target range (50-100 mg/L). METHODS: Ninety-eight children (1-17.6 years, 325 plasma samples) were included in the study. The model was built with NONMEM 7.3. The probability to obtain Ctrough between 50 and 100 mg/L was determined by the Monte Carlo simulations for doses of 20, 30, 40, and 60 mg/kg/day and body weights between 10 and 70 kg...
March 21, 2018: European Journal of Clinical Pharmacology
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