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Valproic acid

Tamanna Jahan Mony, Jae Won Lee, Cheryl Dreyfus, Emanuel DiCicco-Bloom, Hee Jae Lee
Objective: We reported that postnatal exposure of rats to valproic acid (VPA) stimulated proliferation of glial precursors during cortical gliogenesis. However, there are no reports whether enhanced postnatal gliogenesis affects behaviors related to neuropsychiatric disorders. Methods: After VPA treatment during the postnatal day (PND) 2 to PND 4, four behavioral test, such as open field locomotor test, elevated plus maze test, three-chamber social interaction test, and passive avoidance test, were performed at PND 21 or 22...
November 30, 2016: Clinical Psychopharmacology and Neuroscience: the Official Scientific Journal of the Korean College of Neuropsychopharmacology
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
Lei Wu, Hua Feng, Jinhua Hu, Xiangguo Tian, Chunqing Zhang
Due to the low cost and favorable safety profile, valproic acid (VPA) has been considered as a potential candidate drug for therapy of various cancers. Our present study revealed that VPA, at the concentration (1mM) which has no effect on cell proliferation, can significantly increase the in vitro migration and invasion of hepatocarcinoma (HCC) HepG2 and Huh7 cells via induction of epithelial mesenchymal transition (EMT). VPA treatment can significantly increase the mRNA and protein expression of Snail, the key transcription factor of EMT...
October 18, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Peter G Alexander, Karen L Clark, Rocky S Tuan
Limb congenital defects afflict approximately 0.6:1000 live births. In addition to genetic factors, prenatal exposure to drugs and environmental toxicants, represents a major contributing factor to limb defects. Examples of well-recognized limb teratogenic agents include thalidomide, warfarin, valproic acid, misoprostol, and phenytoin. While the mechanism by which these agents cause dymorphogenesis is increasingly clear, prediction of the limb teratogenicity of many thousands of as yet uncharacterized environmental factors (pollutants) remains inexact...
October 21, 2016: Birth Defects Research. Part C, Embryo Today: Reviews
Andrew Kl Goey, Tristan M Sissung, Cody J Peer, William D Figg
The histone deacetylase inhibitor valproic acid (VPA) has been used for many decades in neurology and psychiatry. The more recent introduction of the histone deacetylase inhibitors (HDIs) belinostat, romidepsin and vorinostat for treatment of hematological malignancies indicates the increasing popularity of these agents. Belinostat, romidepsin and vorinostat are metabolized or transported by polymorphic enzymes or drug transporters. Thus, genotype-directed dosing could improve pharmacotherapy by reducing the risk of toxicities or preventing suboptimal treatment...
October 21, 2016: Pharmacogenomics
Maria Graziella Catalano, Mariateresa Pugliese, Marco Gallo, Enrico Brignardello, Paola Milla, Fabio Orlandi, Paolo Piero Limone, Emanuela Arvat, Giuseppe Boccuzzi, Alessandro Piovesan
Anaplastic thyroid cancer (ATC) has a median survival less than 5 months and, to date, no effective therapy exists. Taxanes have recently been stated as the main drug treatment for ATC, and the histone deacetylase inhibitor valproic acid efficiently potentiates the effects of paclitaxel in vitro. Based on these data, this trial assessed the efficacy and safety of the combination of paclitaxel and valproic acid for the treatment of ATC. This was a randomized, controlled phase II/III trial, performed on 25 ATC patients across 5 centers in northwest Italy...
2016: International Journal of Endocrinology
Ferda Hoşgörler, Didem Keleş, Serpil Tanrıverdi-Akhisaroğlu, Şeniz İnanç, Mustafa Akhisaroğlu, Ülker Cankurt, Zekiye Aydoğdu, Ahmet Deniz Uçar, Oğuz Çetinayak, Gülgün Oktay, Sevil Gönenç Arda
BACKGROUND: Matrix metalloproteinase (MMP) inhibitors decrease inflammation in normal tissues and suppress cancer progress in normal tissues. Valproic acid (VA) and doxycycline (DX) are MMP inhibitors that have radio-protective effects. Their ability to inhibit MMPs in irradiated tissue is unknown and the role of MMPs in radio-protective effects has not been tested to date. AIMS: The purpose of this study was to examine whether administration of VA and DX to rats before irradiation affects tissue inflammation and apoptosis in the early phase of radiation, and whether the effect of these drugs is mediated by MMP inhibition...
September 2016: Balkan Medical Journal
InKyeom Kim
Histone deacetylases (HDACs) act as co-repressors in gene transcription by erasing the acetylation of histones, resulting in epigenetic gene silencing. Recent studies revealed that HDAC inhibitors attenuated blood pressure of several hypertensive animal models such as spontaneously hypertensive rats, hyperaldosteronism rats, angiotensin II-induced hypertensive rats and pulmonary hypertensive rats. Unexpectedly, microarray studies uncovered that administration of HDAC inhibitors decreased expression of some genes for example extracellular matrix proteins, oxidative stress-related proteins, cytokines, chemokines and ion transporters, mostly targets of corticoid receptors...
September 2016: Journal of Hypertension
Edward Chia-Cheng Lai, Cheng-Yang Hsieh, Chien-Chou Su, Yea-Huei Kao Yang, Chin-Wei Huang, Swu-Jane Lin, Soko Setoguchi
We compared persistence of antiepileptic drugs (AEDs) including carbamazepine, oxcarbazepine, gabapentin, lamotrigine, topiramate, valproic acid, and phenytoin in an Asian population with epilepsy.A retrospective cohort study was conducted by analyzing Taiwan's National Health Insurance Research Database (NHIRD). Adult epilepsy patients newly prescribed with AEDs between 2005 and 2009 were included. The primary outcome was persistence, defined as the treatment duration from the date of AED initiation to the date of AED discontinuation, switching, hospitalization due to seizure or disenrollment from databases, whichever came first...
August 2016: Medicine (Baltimore)
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
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
Melissa L Barker-Haliski, Taylor D Heck, E Jill Dahle, Fabiola Vanegas, Timothy H Pruess, Karen S Wilcox, H Steve White
OBJECTIVE: Infection with Theiler's murine encephalomyelitis virus (TMEV) in C57Bl/6J mice induces acute seizures and development of spontaneous recurrent seizures and behavioral comorbidities weeks later. The present studies sought to determine whether acute therapeutic intervention with an anti-inflammatory-based approach could prevent or modify development of TMEV-induced long-term behavioral comorbidities. Valproic acid (VPA), in addition to its prototypical anticonvulsant properties, inhibits histone deacetylase (HDAC) activity, which may alter expression of the inflammasome...
October 14, 2016: Epilepsia
Leila Mnif, Rim Sellami, Jawaher Masmoudi
BACKGROUND: Valproic acid is a mood-stabilizing anticonvulsant. Hepatic injuries are among the occasionally observed adverse effects of this medication. CASE PRESENTATION: We present the case of a 47-year-old man who had bipolar disorder for ten years and treated with valproic acid. He demonstrated elevated serum aminotransferases and ultrasonography revealed that hepatomegaly was suggestive of hepatic steatosis. CONCLUSION: This case report stresses the importance of a complete drug history and the need for clinicians to be aware of the delayed onset of hepatic injuries...
August 15, 2016: Psychopharmacology Bulletin
Upendarrao Golla, Deepthi Joseph, Raghuvir Singh Tomar
Valproic acid (VA) is a pharmacologically important histone deacetylase inhibitor that recently garnered attention as an anticancer agent. Since the molecular mechanisms behind the multiple effects of VA are unclear, this study was aimed to unravel the comprehensive cellular processes affected by VA and its molecular targets in vivo using budding yeast as a model organism. Interestingly, genome-wide transcriptome analysis of cells treated with VA showed differential regulation of 30% of the genome. Functional enrichment analysis of VA transcriptome evidenced alteration of various cellular processes including cell cycle, cell wall biogenesis, DNA repair, ion homeostasis, metabolism, stress response, transport and ribosomal biogenesis, etc...
October 13, 2016: Scientific Reports
Mitsuharu Endo, Guljahan Ubulkasim, Chiho Kobayashi, Reiko Onishi, Atsu Aiba, Yasuhiro Minami
Ror2 receptor tyrosine kinase plays crucial roles in developmental morphogenesis and tissue-/organo-genesis. In the developing brain, Ror2 is expressed in neural stem/progenitor cells (NPCs) and involved in the regulation of their stemness. However, it remains largely unknown about its role in the adult brain. In this study, we show that Ror2 is up-regulated in reactive astrocytes in the neocortices within 3 days following stab-wound injury. Intriguingly, Ror2-expressing astrocytes were detected primarily at the area surrounding the injury site, where astrocytes express Nestin, a marker of NPCs, and proliferate in response to injury...
October 11, 2016: Glia
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
Łukasz Fijałkowski, Kinga Sałat, Adrian Podkowa, Paula Zaręba, Alicja Nowaczyk
The chemical interaction of nine antiepileptic drugs (tiagabine, gabapentin, pregabalin, lamotrigine, zonisamide, valproic acid, valpromide, vigabatrin, progabide) and two endogenous metabolites (4-aminobutanoic acid, 4-hydroxybutanoic acid) with a model of human GABA transporter 1 (hGAT1) is described using the molecular docking method. To establish the role of hGAT1 in chronic pain, tiagabine, a selective hGAT1 inhibitor, was assessed in the in vivo experiments for its antiallodynic properties in two mouse models of neuropathic pain...
October 6, 2016: European Journal of Pharmaceutical Sciences
Sungji Ha, Hyunjun Park, Usman Mahmood, Jeong Chan Ra, Yoo-Hun Suh, Keun-A Chang
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by impairments in social interaction and communication, and patients often display co-occurring repetitive behaviors. Although the global prevalence of ASD has increased over time, the etiology and treatments for ASD are poorly understood. Recently, some researchers have suggested that stem cells have therapeutic potential for ASD. Thus, in the present study, we investigated the therapeutic effects of human adipose-derived stem cells (hASCs), a kind of autologous mesenchymal stem cells (MSCs) isolated from adipose tissue, on valproic acid (VPA)-induced autism model mice...
October 4, 2016: Behavioural Brain Research
Neila Fathallah, Chayma Ladhari, Raoudha Slim, Najet Ghariani, Badreddine Sriha, Chaker Ben Salem
Drug-associated immune-complex vasculitis induced by antiepileptics is a rare adverse drug reaction, more frequently reported with carbamazepine, valproic acid and phenytoin. Phenobarbital has not been previously reported to induce vasculitis. We report a cutaneous vasculitis induced by phenobarbital with cross-reactivity to carbamazepine in an 18-year-old epileptic patient. Carbamazepine and phenobarbital are both aromatic antiepileptic drugs with similarity in their chemical structure. Cross-reactivity is a frequently reported effect between these drugs following adverse skin reactions...
September 15, 2016: Thérapie
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
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