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https://www.readbyqxmd.com/read/29791065/risk-factors-of-valproic-acid-induced-hyperammonaemia-in-chinese-paediatric-patients-with-epilepsy
#1
Xu Zhu, Xinlin Li, Ti Zhang, Limei Zhao
The present study was aimed at identifying genetic and non-genetic risk factors for valproic acid (VPA)-induced hyperammonaemia in Chinese paediatric patients with epilepsy. A total of 210 epileptic patients, treated with VPA as monotherapy, were enrolled and classified into hyperammonaemia and control groups according to their blood ammonia level (cut-off value 50 μmol/L). Serum concentrations of VPA and its major metabolites were simultaneously determined by ultra-high performance liquid chromatography-tandem mass spectrometry...
May 23, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29787924/sleep-architecture-and-epileptic-characteristics-of-drug-na%C3%A3-ve-patients-in-childhood-absence-epilepsy-spectrum-a-prospective-study
#2
Argirios Dinopoulos, Maria A Tsirouda, Anastasios Bonakis, Roser Pons, Ioanna D Pavlopoulou, Konstantinos Tsoumakas
PURPOSE: Childhood absence epilepsy (CAE) is an epileptic syndrome presenting between 2nd-10th years. The spells are elicited with hyperventilation (HV) while sleep seems to exacerbate the electrical activity. Our aim is to describe sleep architecture and its relationship with epileptic discharges (EDs) in patients with CAE, before treatment and one year later. METHODS: Twenty-eight, drug-naive children were recruited (21 girls), mean age 90.1 ± 32.6 months...
April 30, 2018: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/29787319/usefulness-of-multiple-electrode-aggregometry-as-a-screening-tool-for-bleeding-disorders-in-a-pediatric-hospital
#3
Thorsten Haas, Melissa M Cushing, Stephanie Varga, Séverine Gilloz, Markus Schmugge
Platelet function testing is a cornerstone in the diagnostic investigation of patients with a bleeding history. Multiple electrode aggregometry (MEA) has been shown to detect von Willebrand disease (VWD), platelet function disorders, and drug-induced bleeding disorders. However, there are few studies supporting its successful use in children. We have implemented and used MEA over 3 years in our hemostasis laboratory in order to study its usefulness to supplement and expedite diagnosis. This is a retrospective, single-center, cohort study of 109 hospitalized children who underwent a laboratory investigation of hemostasis and either had a reported bleeding history or an abnormal bleeding episode...
May 22, 2018: Platelets
https://www.readbyqxmd.com/read/29785653/valproic-acid-treatment-response-in-vitro-is-determined-by-tp53-status-in-medulloblastoma
#4
Bruna Mascaro-Cordeiro, Indhira Dias Oliveira, Francine Tesser-Gamba, Lorena Favaro Pavon, Nasjla Saba-Silva, Sergio Cavalheiro, Patrícia Dastoli, Silvia Regina Caminada Toledo
PURPOSE: Histone deacetylate inhibitors (HDACi), as valproic acid (VA), have been reported to enhance efficacy and to prevent drug resistance in some tumors, including medulloblastoma (MB). In the present study, we investigated VA role, combined to cisplatin (CDDP) in cell viability and gene expression of MB cell lines. METHODS: Dose-response curve determined IC50 values for each treatment: (1) VA single, (2) CDDP single, and (3) VA and CDDP combined. Cytotoxicity and flow cytometry evaluated cell viability after exposure to treatments...
May 22, 2018: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/29782159/reduced-zebrafish-transcriptome-atlas-toward-understanding-the-environmental-neurotoxicants
#5
Kun Zhang, Yanbin Zhao
Transcriptomic approaches monitoring gene responses at genome-scale are increasingly used in toxicological research and help to clarify the molecular mechanisms of adverse effects caused by environmental toxicants. However, their applications for chemical assessment are hampered due to high expenses required and more importantly the lack of in-depth data mining and mechanistic perspectives. Here, we described a Reduced Transcriptome Atlas (RTA) approach which integrates transcriptomic datasets and a comprehensive panel of genes generated to represent neurogenesis and the early neuronal development of zebrafish, to determine the potential neurodevelopmental toxicities of environmental chemicals...
May 21, 2018: Environmental Science & Technology
https://www.readbyqxmd.com/read/29778792/valproic-acid-attenuates-manganese-induced-reduction-in-expression-of-glt-1-and-glast-with-concomitant-changes-in-murine-dopaminergic-neurotoxicity
#6
James Johnson, Edward Pajarillo, Pratap Karki, Judong Kim, Deok-Soo Son, Michael Aschner, Eunsook Lee
Exposure to elevated levels of manganese (Mn) causes manganism, a neurological disorder with similar characteristics to those of Parkinson's disease (PD). Valproic acid (VPA), an antiepileptic, is known to inhibit histone deacetylases and exert neuroprotective effects in many experimental models of neurological disorders. In the present study, we investigated if VPA attenuated Mn-induced dopaminergic neurotoxicity and the possible mechanisms involved in VPA's neuroprotection, focusing on modulation of astrocytic glutamate transporters (glutamate aspartate transporter, GLAST and glutamate transporter 1, GLT-1) and histone acetylation in H4 astrocyte culture and mouse models...
May 17, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29776446/valproic-acid-attenuates-traumatic-spinal-cord-injury-induced-inflammation-via-stat1-and-nf-%C3%AE%C2%BAb-pathway-dependent-of-hdac3
#7
Shoubo Chen, Jingfang Ye, Xiangrong Chen, Jinnan Shi, Wenhua Wu, Wenping Lin, Weibin Lin, Yasong Li, Huangde Fu, Shun Li
BACKGROUND: Microglial polarization with M1/M2 phenotype shifts and the subsequent neuroinflammatory responses are vital contributing factors for spinal cord injury (SCI)-induced secondary injury. Nuclear factor-κB (NF-κB) is considered the central transcription factor of inflammatory mediators, which plays a crucial role in microglial activation. Lysine acetylation of STAT1 seems necessary for NF-kB pathway activity, as it is regulated by histone deacetylases (HDACs). There have been no studies that have explained if HDAC inhibition by valproic acid (VPA) affects the NF-κB pathway via acetylation of STAT1 dependent of HDAC activity in the microglia-mediated central inflammation following SCI...
May 18, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29775723/a-scale-out-approach-towards-neural-induction-of-human-induced-pluripotent-stem-cells-for-neurodevelopmental-toxicity-studies
#8
Cláudia C Miranda, Tiago G Fernandes, Sandra N Pinto, Manuel Prieto, M Margarida Diogo, Joaquim M S Cabral
Stem cell's unique properties confer them a multitude of potential applications in the fields of cellular therapy, disease modelling and drug screening fields. In particular, the ability to differentiate neural progenitors (NP) from human induced pluripotent stem cells (hiPSCs) using chemically-defined conditions provides an opportunity to create a simple and straightforward culture platform for application in these fields. Here, we demonstrated that hiPSCs are capable of undergoing neural commitment inside microwells, forming characteristic neural structures resembling neural rosettes and further give rise to glial and neuronal cells...
May 15, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29772401/evaluation-ofserum-free-carnitine-acylcarnitine-levels-and-left-ventricular-systolic-functions-in-children-with-idiopathic-epilepsy-receiving-valproic-acid
#9
Ilknur Kulhas Celik, Haydar Ali Tasdemir, Hülya Ince, Halil Celik, Metin Sungur
OBJECTIVES: In the study, the effect of valproic acid on serum free/acylcarnitine levels and left ventricular systolic function in pediatric patients with idiopathic epilepsy receiving valproic acid was investigated. PATIENTS AND METHODS: Patients receiving valproic acid treatment for six months between January 2012 and December 2012 were evaluated. Blood samples were obtained from the participants twice (pretreatment and the sixth month of treatment) and serum-free and acylcarnitine levels (from C2 to C18:1-OH) were measured using tandem mass spectrometry...
May 14, 2018: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/29767267/hdac-inhibitors-trichostatin-a-and-valproic-acid-increase-e%C3%A2-cadherin-and-vimentin-expression-but-inhibit-migration-and-invasion-of-cholangiocarcinoma-cells
#10
Joon Ho Wang, Eun Jeoung Lee, Meiying Ji, Seon Mee Park
The effects of histone deacetylase (HDAC) inhibitors on epithelial-mesenchymal transition (EMT) differ in various cancers. E‑cadherin is a cell‑to‑cell adhesion protein, whereas accumulation of vimentin is related to the development of the spindle shape of the mesenchymal cell phenotype. We investigated the EMT phenotypes of human cholangiocellular carcinoma HuCC‑T1, JCK and SNU‑1079 cell lines. To this end, we measured the expression of E‑cadherin or zonula occludens (ZO)‑1 and vimentin, epithelial and mesenchymal cell markers, respectively, using real‑time reverse transcription‑polymerase chain reaction, western blotting, and immunofluorescence microscopy following treatment with trichostatin A (TSA, 200 nM) or valproic acid (VPA, 0...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29765217/allergy-to-chlorpromazine-and-valproic-acid-following-carbamazepine-hypersensitivity-in-a-patient-with-an-hla-b-4601-allele
#11
Kumi Sakurada, Takeshi Kozaru, Kazuo Yamada, Masashi Nibuya, Kiyoshi Nagata, Eiji Suzuki
A 73-year-old man, exhibiting psychomotor excitement after traumatic brain injury, developed allergic cutaneous eruptions and hepatic inflammation that did not resolve after the cessation of carbamazepine (CBZ). Fusing maculopapular erythema was observed in the face, neck, presternal region, and bilaterally in the forearms and feet. A drug-induced lymphocyte stimulation test revealed hypersensitivity to chlorpromazine (CPZ) and valproic acid (VPA), as well as to CBZ. The allergic reaction with eosinophilia to CPZ and VPA was suspected to have emerged following CBZ hypersensitivity, since previous treatment with CPZ and VPA prior to the introduction of CBZ had not been associated with adverse reactions earlier in the course of treatment...
2018: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/29762671/motor-impairments-correlate-with-social-deficits-and-restricted-neuronal-loss-in-an-environmental-model-of-autism
#12
Tareq Al Sagheer, Obelia Haida, Anais Balbous, Maureen Francheteau, Emmanuel Matas, Pierre-Olivier Fernagut, Mohamed Jaber
Background: Motor impairments are amongst the earliest and most consistent signs of autism spectrum disorders (ASD) but are not used as diagnostic criteria. In addition, the relationship between motor and cognitive impairments and their respective neural substrates remain unknown. Methods: Here, we aimed at determining whether a well-acknowledged animal model of ASD, the valproic acid (VPA) model, displays motor impairments and whether they may correlate with social deficits and neuronal loss within motor brain areas...
May 12, 2018: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29759727/valproic-acid-induces-three-novel-cytotoxic-secondary-metabolites-in-diaporthe-sp-an-endophytic-fungus-from-datura-inoxia-mill
#13
Vishal Sharma, Venugopal Singamaneni, Nisha Sharma, Amit Kumar, Divya Arora, Manoj Kushwaha, Shashi Bhushan, Sundeep Jaglan, Prasoon Gupta
Addition of the valproic acid (histone deacetylases inhibitor) to a culture of an endophytic fungus Diaporthe sp. harbored from Datura inoxia significantly altered its secondary metabolic profile and resulted in the isolation of three novel compounds, identified as xylarolide A (1), diportharine A (2) and xylarolide B (3) along with one known compound xylarolide (4). The structures of all the compounds (1-4) were determined by detailed analysis of 1D and 2D NMR spectroscopic data. The relative configurations of compounds 1-3 were determined with the help of NOESY data and comparison of optical rotations with similar compounds with established stereochemistry...
April 10, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29756335/treatment-of-restless-legs-syndrome-evidence-based-review-and-implications-for-clinical-practice-revised-2017-%C3%A2
#14
REVIEW
Juliane Winkelmann, Richard P Allen, Birgit Högl, Yuichi Inoue, Wolfgang Oertel, Aaro V Salminen, John W Winkelman, Claudia Trenkwalder, Cristina Sampaio
The objective of the current review was to update the previous evidence-based medicine review of treatments for restless legs syndrome published in 2008. All randomized, controlled trials (level I) with a high quality score published between January 2007 and January 2017 were reviewed. Forty new studies qualified for efficacy review. Pregabalin, gabapentin enacarbil, and oxycodone/naloxone, which did not appear in the previous review, have accrued data to be considered efficacious. Likewise, new data enable the modification of the level of efficacy for rotigotine from likely efficacious to efficacious...
May 14, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29752814/valproic-acid-inhibits-atp-triggered-ca-2-release-via-a-p38-dependent-mechanism-in-bend-3-endothelial-cells
#15
Iat-Lon Leong, Tien-Yao Tsai, Kar-Lok Wong, Lian-Ru Shiao, Ka-Shun Cheng, Paul Chan, Yuk-Man Leung
Valproic acid (VA) is currently used to treat epilepsy and bipolar disorder. It has also been demonstrated to promote neuroprotection and neurogenesis. Although beneficial actions of VA on brain blood vessels have also been demonstrated, the effects of VA on brain endothelial cell (EC) Ca2+ signaling is hitherto unreported. In this report we examined the effects of VA on agonist-triggered Ca2+ signaling in mouse cortical bEND.3 EC. While VA (100 μM) did not cause an acute inhibition of ATP-triggered Ca2+ signaling, a 30-min VA treatment strongly suppressed ATP-triggered intracellular Ca2+ release; however, such treatment did not affect Ca2+ release triggered by cyclopiazonic acid, an inhibitor of SERCA Ca2+ pump, suggesting there was no reduction in Ca2+ store size...
May 12, 2018: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29750337/lamotrigine-resistant-corneal-kindled-mice-a-model-of-pharmacoresistant-partial-epilepsy-for-moderate-throughput-drug-discovery
#16
Zachery Koneval, Kevin M Knox, H Steve White, Melissa Barker-Haliski
OBJECTIVE: Despite numerous treatments for epilepsy, over 30% of patients remain resistant to available antiseizure drugs (ASDs). Thus, there is a strong need for more effective ASDs for these individuals. Early ASD discovery has historically relied on acute in vivo seizure models (maximal electroshock, subcutaneous pentylenetetrazol, 6 Hz), which lack the pathophysiology that defines chronic epilepsy. Etiologically relevant rodent models of pharmacoresistant epilepsy exist (eg, phenytoin (PHT)- and lamotrigine (LTG)-resistant amygdala-kindled rat and focal kainic acid mouse), but these models are resource- and labor-intensive and thus unsuitable for frontline ASD discovery...
May 11, 2018: Epilepsia
https://www.readbyqxmd.com/read/29750329/biodegradation-of-lignin-monomers-vanillic-p-coumaric-and-syringic-acid-by-the-bacterial-strain-sphingobacterium-sp-hy-h
#17
Jinxing Wang, Jidong Liang, Sha Gao
Many bacterial strains have been demonstrated to biodegrade lignin for contaminant removal or resource regeneration. The goal of this study was to investigate the biodegradation amount and associated pathways of three lignin monomers, vanillic, p-coumaric, and syringic acid by strain Sphingobacterium sp. HY-H. Vanillic, p-coumaric, and syringic acid degradation with strain HY-H was estimated as 88.71, 76.67, and 72.78%, respectively, after 96 h. Correspondingly, the same three monomers were associated with a COD removal efficiency of 87...
May 10, 2018: Current Microbiology
https://www.readbyqxmd.com/read/29748578/publisher-correction-valproic-acid-sensitizes-hepatocellular-carcinoma-cells-to-proton-therapy-by-suppressing-nrf2-activation
#18
Jeong Il Yu, Changhoon Choi, Sung-Won Shin, Arang Son, Ga-Haeng Lee, Shin-Yeong Kim, Hee Chul Park
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
May 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29748111/dat-spect-imaging-in-cases-of-drug-induced-parkinsonism-in-a-specialty-movement-disorders-practice
#19
Jacob Yomtoob, Kimberly Koloms, Danny Bega
OBJECTIVE: Compare clinical characteristics and outcomes in cases where DAT-SPECT imaging is used to distinguish Parkinson's disease from Drug-Induced Parkinsonsim. BACKGROUND: Clinical uncertainty in diagnosing Parkinson's disease is common when patients are on dopamine-blocking medications. DAT-SPECT imaging can improve diagnostic certainty but little data are available on clinical characteristics and outcomes associated with normal and abnormal scan results. METHODS: Retrospective chart review of patients seen at a movement disorders center between 2011 and 2017 where DAT-SPECT was ordered to distinguish Parkinson's disease from Drug-induced Parkinsonism...
May 5, 2018: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29746395/a-liquid-chromatography-mass-spectrometry-assay-for-determination-of-perampanel-and-concomitant-antiepileptic-drugs-in-the-plasma-of-patients-with-epilepsy-compared-with-a-fluorescent-hplc-assay
#20
Ugo de Grazia, Annachiara D'Urso, Federica Ranzato, Valentina De Riva, Giorgia Contarato, Giuseppe Billo, Francesco Perini, Elisabetta Galloni
BACKGROUND: Perampanel is a novel non-competitive selective antagonist at the postsynaptic ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) glutamate receptor, approved as an adjunctive agent for the treatment of partial-onset seizure with or without secondary generalization and for primary generalized tonic-clonic seizure in patients with epilepsy who are at least 12 years of age. Limited information is available about the clinical utility of therapeutic drug monitoring of perampanel and therapeutic ranges are so far not established...
May 9, 2018: Therapeutic Drug Monitoring
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