1,772 results match your criteria Toxicity Valproate


Metro-SMHOP 01: Metronomics combination with cyclophosphamide-etoposide and valproic acid for refractory and relapsing pediatric malignancies.

Pediatr Blood Cancer 2020 Jul 13:e28508. Epub 2020 Jul 13.

Paediatric Haematology and Oncology Department, La Timone Children's Hospital, Assistance Publique Hopitaux de Marseille, Marseille, France.

Background: In low- and middle-income countries, therapeutic options for advanced, refractory, or relapsing malignancies are limited due to local constraints such as cost of drugs, distance from oncology centers, and lack of availability of new anticancer drugs. Metronomics, which combines metronomic chemotherapy (MC) and drug repositioning, allows for the provision of new therapeutic options for patients in this setting.

Aim Of The Study: To evaluate the activity and toxicity of a metronomic regimen in Moroccan pediatric patients with refractory or relapsing malignancies. Read More

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http://dx.doi.org/10.1002/pbc.28508DOI Listing

Synthetic and therapeutic perspectives of nitrogen containing heterocycles as anti-convulsants.

Bioorg Med Chem 2020 Aug 13;28(15):115585. Epub 2020 Jun 13.

Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Ghal Kalan, Ferozpur G.T. Road MOGA-142001, Punjab, India. Electronic address:

Epilepsy is one of the commonly prevailing neurological disorders. According to the reports, it is evident that about 80% of the epileptic cases have been observed in developing countries. Although there are many drugs with significant potency available in the market; still there is an issue of selectivity and toxicity. Read More

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http://dx.doi.org/10.1016/j.bmc.2020.115585DOI Listing

Valproic acid promotes mitochondrial dysfunction in primary human hepatocytes in vitro; impact of C/EBPα-controlled gene expression.

Arch Toxicol 2020 Jul 4. Epub 2020 Jul 4.

Maastricht University, Maastricht, The Netherlands.

Valproic acid (VPA) is a frequently prescribed anti-epileptic drug which is known to cause liver toxicity and steatosis through mitochondrial dysfunction. Nevertheless the mechanisms underlying these adverse effects are incompletely understood. In this study, we determined the effect of relatively short (3 h) or prolonged (72 h) exposure to VPA on mitochondrial function in primary human hepatocytes (PHHs). Read More

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http://dx.doi.org/10.1007/s00204-020-02835-xDOI Listing

Gaze-evoked nystagmus associated with valproic acid-induced lamotrigine toxicity.

Clin Neurol Neurosurg 2020 Jun 20;196:106013. Epub 2020 Jun 20.

Department of Neurology, Korea University College of Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea. Electronic address:

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http://dx.doi.org/10.1016/j.clineuro.2020.106013DOI Listing
June 2020
1.248 Impact Factor

Meropenem for management of valproic acid overdose: a case report.

Drug Metab Pers Ther 2020 Jun 30. Epub 2020 Jun 30.

Hospital Base de Valdivia, Valdivia, Chile.

Objectives Valproic acid (VPA) is an anticonvulsant used in several clinical scenarios. VPA has been increasingly associated with intentional or unintentional overdose. In patients presenting with severe VPA overdose, supportive care and airway protection are cornerstones of treatment, while levocarnitine is suggested in patients with hyperammonemia and hemodialysis is recommended in patients with VPA serum concentrations (SC) >1,300 mg/L and presence of cerebral edema or shock. Read More

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http://dx.doi.org/10.1515/dmpt-2019-0028DOI Listing

An EEG system to detect brain signals from multiple adult zebrafish.

Biosens Bioelectron 2020 Sep 23;164:112315. Epub 2020 May 23.

Department of Robotics Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea. Electronic address:

Zebrafish has been widely used as an experimental animal in many biological processes to study brain functions, neurological disorders and drug toxicity. Electroencephalogram (EEG), which directly measures brain activities, has been used to diagnose and study neurological disorders. Previous studies have recorded EEG signals from adult zebrafish, but the recordings have been only possible from a single individual. Read More

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http://dx.doi.org/10.1016/j.bios.2020.112315DOI Listing
September 2020

Radiosensitizers in the temozolomide era for newly diagnosed glioblastoma.

Neurooncol Pract 2020 Jun 30;7(3):268-276. Epub 2019 Nov 30.

Radiation Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA.

Glioblastoma (GBM) is a challenging diagnosis with almost universally poor prognosis. Though the survival advantage of postoperative radiation (RT) is well established, around 90% of patients will fail in the RT field. The high likelihood of local failure suggests the efficacy of RT needs to be improved to improve clinical outcomes. Read More

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http://dx.doi.org/10.1093/nop/npz057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7274183PMC

Acute respıratory dıstress syndrome(ARDS) after valproıc acıd toxıcıty ın the ıntensıve care unıt: Case report.

Bipolar Disord 2020 Jun 11. Epub 2020 Jun 11.

Health and Science University, Konya Training and Research Hospital, Brain and Nerve Surgery Department, Turkey.

Valproic acid (VPA) is a broad-spectrum antiepileptic drug. It has been widely used in bipolar disorder treatment for many years. Although treatment is generally well tolerated, serious complications such as hemorrhagic pancreatitis, bone marrow suppression, hepatotoxicity and encephalopathy can occur. Read More

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http://dx.doi.org/10.1111/bdi.12951DOI Listing

Caprylic (Octanoic) Acid as a Potential Fatty Acid Chemotherapeutic for Glioblastoma.

Prostaglandins Leukot Essent Fatty Acids 2020 May 30;159:102142. Epub 2020 May 30.

Department of Biology, Boston College, Boston, United States.

High grade glial tumors (HGGs) including anaplastic astrocytoma (WHO Grade-III) and glioblastoma multiforme (GBM, WHO Grade-IV) are among the most malignant cancers known to man. Due to their defective mitochondria, HGG cells consume glucose via glycolysis even in the presence of oxygen. Overall survival is worse in HGG patients that are hyperglycemic. Read More

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http://dx.doi.org/10.1016/j.plefa.2020.102142DOI Listing

Anti-seizure therapy with a long-term, implanted intra-cerebroventricular delivery system for drug-resistant epilepsy: A first-in-man study.

EClinicalMedicine 2020 May 3;22:100326. Epub 2020 May 3.

Cerebral Therapeutics, 12635 E. Montview Blvd., Aurora, CO 80010, Australia.

Background: A clinical feasibility study was undertaken at a single center of long-term intra-cerebroventricular drug delivery of the anti-seizure medication valproic acid, into the cerebrospinal fluid (CSF) in order to treat drug resistant focal seizures, using an implantable infusion system. The primary objective was to establish the dose range of VPA administered in this manner. Secondarily, safety, pharmacokinetics (PK) and a preliminary estimate of effectiveness were evaluated. Read More

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http://dx.doi.org/10.1016/j.eclinm.2020.100326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205744PMC

Anti-epileptic activity, toxicity and teratogenicity in CD1 mice of a novel valproic acid arylamide derivative, N-(2-hydroxyphenyl)-2-propylpentanamide.

Toxicol Appl Pharmacol 2020 Jul 7;399:115033. Epub 2020 May 7.

Laboratorio de Toxicología Preclínica, Departamento de Farmacia, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Av. Wilfrido Massieu, Col. Zacatenco, Del. Gustavo A. Madero, Ciudad de México 07738, Mexico.

N-(2-hydroxyphenyl)-2-propylpentamide (HO-AAVPA) is a novel arylamide derivative of valproic acid (VPA) designed in silico, with better antioxidant and antiproliferative effect on cancer cell lines than VPA. This study was aimed to evaluate the anticonvulsant activity, the toxicity and teratogenicity produced in HO-AAVPA-treated CD1 mice using VPA as positive control. With the maximal electroshock (MES)- and pentylenetetrazole (PTZ)-induced seizure models, HO-AAVPA reduced the time of hind limb extension, stupor and recovery, the number of clonic and tonic seizures and the mortality rate in a dose-dependent manner, obtaining an ED of 370 and 348 mg/kg for MES and PTZ, respectively. Read More

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http://dx.doi.org/10.1016/j.taap.2020.115033DOI Listing

Thymoquinone could be protective against valproic acid-induced testicular toxicity by antioxidant and anti-inflammatory mechanisms.

Andrologia 2020 Aug 4;52(7):e13623. Epub 2020 May 4.

Department of Medical Biology, Faculty of Medicine, Adiyaman University, Adiyaman, Turkey.

Although valproic acid (VPA) is a low-cost and effective drug, it is known to cause organ toxicity via oxidative stress and related process. In present study, we aimed to evaluate the possible protective effects of thymoquinone (TMQ) on VPA-induced testicular toxicity. Male Sprague-Dawley rats were divided into three as control, VPA (500 mg kg  day ) for 14 days and VPA plus TMQ (50 mg kg  day for 14 days) with seven rats in. Read More

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http://dx.doi.org/10.1111/and.13623DOI Listing

Targeting Breast Cancer Cells with G4 PAMAM Dendrimers and Valproic Acid Derivative Complexes.

Anticancer Agents Med Chem 2020 Apr 22. Epub 2020 Apr 22.

Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotécnológica (Laboratory for the Design and Development of New Drugs and Biotechnological Innovation) de la Escuela Superior de Medicina, Instituto Politécnico Nacional, México. Plan de San Luis Y Díaz Mirón S/N, Col. Casco de Santo Tomas, México City. Mexico.

Background: Our research group has developed some Valproic Acid (VPA) derivatives employed as antiproliferative compounds targeting HDAC8 enzyme. However, some of these compounds are poorly water soluble.

Objective: Furthermore, we employed the four generation of Polyamidoamine (G4 PAMAM) dendrimers as drug carrier of these compounds to increase their water solubility for further in vitro evaluation. Read More

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http://dx.doi.org/10.2174/1871520620666200423073812DOI Listing

Combination of Arsenic Trioxide and Valproic Acid Efficiently Inhibits Growth of Lung Cancer Cells via G2/M-Phase Arrest and Apoptotic Cell Death.

Int J Mol Sci 2020 Apr 10;21(7). Epub 2020 Apr 10.

Department of Physiology, Medical School, Research Institute for Endocrine Sciences, Chonbuk National University, 20 Geonji-ro, Deokjin-gu, Jeonju, Jeollabuk 54907, Korea.

Arsenic trioxide (ATO; AsO) has anti-cancer effects in various solid tumors as well as hematological malignancy. Valproic acid (VPA), which is known to be a histone deacetylase inhibitor, has also anti-cancer properties in several cancer cells including lung cancer cells. Combined treatment of ATO and VPA (ATO/VPA) could synergistically enhance anti-cancer effects and reduce ATO toxicity ATO. Read More

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http://dx.doi.org/10.3390/ijms21072649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177455PMC

A novel screening test to predict the developmental toxicity of drugs using human induced pluripotent stem cells.

Authors:
Nobuo Aikawa

J Toxicol Sci 2020 ;45(4):187-199

Translational Research Unit, R&D Division, Kyowa Kirin Co., Ltd.

In vitro human induced pluripotent stem (iPS) cells testing (iPST) to assess developmental toxicity, e.g., the induction of malformation or dysfunction, was developed by modifying a mouse embryonic stem cell test (EST), a promising animal-free approach. Read More

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http://dx.doi.org/10.2131/jts.45.187DOI Listing
January 2020

Valproic Acid-Induced Hyperammonemic Encephalopathy in a Patient with Bipolar Disorder: A Case Report.

Brain Sci 2020 Mar 24;10(3). Epub 2020 Mar 24.

Department of Psychiatry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan.

Valproic acid (VPA) is widely used to control various seizure disorders and psychiatric disorders. Valproic acid-induced hyperammonemic encephalopathy (VHE) is a rare but dangerous complication of VPA-induced toxicity. For this case report, several risk factors were identified, including young age, polytherapy regimens, VPA overdose, poor liver function, and carnitine deficiency. Read More

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http://dx.doi.org/10.3390/brainsci10030187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139302PMC

Protective effects of valproic acid on 6-hydroxydopamine-induced neuroinjury.

Environ Toxicol 2020 Aug 13;35(8):840-848. Epub 2020 Mar 13.

Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.

Oxidative stress may play critically important roles in the etiology of Parkinson's disease (PD). 6-Hydroxydopamine (6-OHDA) is a physiological neurotoxin reported to induce oxidative-induced apoptosis of dopaminergic neurons in PD mice models. Valproic acid (VPA), a clinical mood stabilizer, is a HDAC inhibitor with neuroprotective capacities. Read More

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http://dx.doi.org/10.1002/tox.22920DOI Listing

Ellagic acid attenuates liver toxicity induced by valproic acid in rats.

J Pharmacol Sci 2020 May 29;143(1):23-29. Epub 2020 Jan 29.

Department of Pharmacology, Misr University for Science and Technology (MUST), 6 October, Egypt.

Valproic acid is a commonly used drug for many psychiatric disorders, particularly for epilepsy. However, it has been reported that its use is associated with possible side effects including hepatotoxicity. The present study investigated the hepatoprotective effect of ellagic acid against valproic acid-induced hepatotoxicity in rats. Read More

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http://dx.doi.org/10.1016/j.jphs.2020.01.007DOI Listing
May 2020
2.360 Impact Factor

Development of a generic zebrafish embryo PBPK model and application to the developmental toxicity assessment of valproic acid analogs.

Reprod Toxicol 2020 04 28;93:219-229. Epub 2020 Feb 28.

CERTARA UK Limited, Simcyp Division, Level 2-Acero, 1 Concourse Way, Sheffield, S1 2BJ, United Kingdom. Electronic address:

In order to better explain, predict, or extrapolate to humans the developmental toxicity effects of chemicals to zebrafish (Danio rerio) embryos, we developed a physiologically-based pharmacokinetic (PBPK) model designed to predict organ concentrations of neutral or ionizable chemicals, up to 120 h post-fertilization. Chemicals' distribution is modeled in the cells, lysosomes, and mitochondria of ten organs of the embryo. The model's partition coefficients are calculated with sub-models using physicochemical properties of the chemicals of interest. Read More

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http://dx.doi.org/10.1016/j.reprotox.2020.02.010DOI Listing

Histone deacetylase inhibitor pre-treatment enhances the efficacy of DNA-interacting chemotherapeutic drugs in gastric cancer.

World J Gastroenterol 2020 Feb;26(6):598-613

Epigenetics and Chromatin Biology Group, Gupta Laboratory, Cancer Research Institute, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra 410210, India.

Background: The prognosis of gastric cancer continues to remain poor, and epigenetic drugs like histone deacetylase inhibitors (HDACi) have been envisaged as potential therapeutic agents. Nevertheless, clinical trials are facing issues with toxicity and efficacy against solid tumors, which may be partly due to the lack of patient stratification for effective treatments.

Aim: To study the need of patient stratification before HDACi treatment, and the efficacy of pre-treatment of HDACi as a chemotherapeutic drug sensitizer. Read More

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http://dx.doi.org/10.3748/wjg.v26.i6.598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029347PMC
February 2020

Delirium Secondary to Lamotrigine Toxicity.

Curr Drug Saf 2020 ;15(2):156-159

Mental Health and Behavioral Sciences Service, James A. Haley Veterans Hospital, Tampa, FL, United States.

Background: Lamotrigine is a phenyltriazine medication that has been approved by the United States Food and Drug Administration as monotherapy and as an adjunctive agent for the treatment of seizure disorder. It was later approved by the FDA for the treatment of bipolar disorder. Lamotrigine is generally well tolerated by patients, but some serious symptoms can occur during treatment. Read More

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http://dx.doi.org/10.2174/1574886315666200225111057DOI Listing
January 2020

Integration of read-across and artificial neural network-based QSAR models for predicting systemic toxicity: A case study for valproic acid.

J Toxicol Sci 2020 ;45(2):95-108

Shiseido Global Innovation Center.

We present a systematic, comprehensive and reproducible weight-of-evidence approach for predicting the no-observed-adverse-effect level (NOAEL) for systemic toxicity by using read-across and quantitative structure-activity relationship (QSAR) models to fill gaps in rat repeated-dose and developmental toxicity data. As a case study, we chose valproic acid, a developmental toxicant in humans and animals. High-quality in vivo oral rat repeated-dose and developmental toxicity data were available for five and nine analogues, respectively, and showed qualitative consistency, especially for developmental toxicity. Read More

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http://dx.doi.org/10.2131/jts.45.95DOI Listing
January 2020

A Novel Correction Equation Avoids High-Magnitude Errors in Interpreting Therapeutic Drug Monitoring of Phenytoin among Critically Ill Patients.

Ther Drug Monit 2020 Feb 10. Epub 2020 Feb 10.

Division of Neurocritical Care and Emergency Neurology, Massachusetts General Hospital, Boston, MA.

Background: Phenytoin has a narrow therapeutic index and the potential of under-treatment or toxicity. Available equations are used to correct for the impact of hypoalbuminemia on unbound (free) phenytoin levels. The authors aimed to determine the accuracy of equations used to estimate free phenytoin in hospitalized patients and assess the impact of using additional clinical data. Read More

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http://dx.doi.org/10.1097/FTD.0000000000000739DOI Listing
February 2020

Antiepileptic Overdose.

Authors:
Shakuntala Murty

Indian J Crit Care Med 2019 Dec;23(Suppl 4):S290-S295

Department of Emergency Medicine, St. John's Medical College and Hospital, Bengaluru, Karnataka, India.

Antiepileptics include various groups of drugs that have different mechanisms of actions and adverse effects. They are often also used to treat other disorders such as psychosis, chronic pain, and migraine. The most common drugs implicated in overdose include phenytoin, sodium valproate, carbamazepine, and phenobarbital. Read More

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http://dx.doi.org/10.5005/jp-journals-10071-23301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996662PMC
December 2019

Meropenem as an antidote for intentional valproic acid overdose.

Am J Emerg Med 2020 03 8;38(3):690.e1-690.e2. Epub 2020 Jan 8.

Pharmacy Department, AdventHealth Orlando, 601 E Rollins St, Orlando, 32803, FL, USA. Electronic address:

Valproic acid (VPA) is a broad-spectrum antiepileptic drug indicated for monotherapy and adjunctive therapy of seizures, and complex manic episodes associated with bipolar disorder [1]. While uncommon due to monitoring, VPA can cause toxicity at supratherapeutic levels [1, 2]. Traditional treatment for VPA toxicity is primarily supportive care, however activated charcoal, l-carnitine, and hemodialysis have been successful in removing free VPA [2]. Read More

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http://dx.doi.org/10.1016/j.ajem.2019.09.011DOI Listing

The mitochondrial epilepsies.

Eur J Paediatr Neurol 2020 Jan 7;24:47-52. Epub 2020 Jan 7.

Wellcome Centre for Mitochondrial Research, Institute of Neuroscience, Newcastle University, Newcastle-Upon-Tyne, NE2 4HH, United Kingdom; Department of Neurology, Royal Victoria Infirmary, Queen Victoria Rd, Newcastle-Upon-Tyne, NE1 4LP, United Kingdom; Institute of Neuroscience, Henry Wellcome Building, Framlington Place, Newcastle University, Newcastle-Upon-Tyne, NE2 4HH, United Kingdom. Electronic address:

Mitochondria are vital organelles within cells that undertake many important metabolic roles, the most significant of which is to generate energy to support organ function. Dysfunction of the mitochondrion can lead to a wide range of clinical features, predominantly affecting organs with a high metabolic demand such as the brain. One of the main neurological manifestations of mitochondrial disease is metabolic epilepsies. Read More

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http://dx.doi.org/10.1016/j.ejpn.2019.12.021DOI Listing
January 2020

Butyrate prevents valproate-induced liver injury: In vitro and in vivo evidence.

FASEB J 2020 01 26;34(1):676-690. Epub 2019 Nov 26.

Department of Pharmacy, University of Naples Federico II, Naples, Italy.

Sodium valproate (VPA), an antiepileptic drug, may cause dose- and time-dependent hepatotoxicity. However, its iatrogenic molecular mechanism and the rescue therapy are disregarded. Recently, it has been demonstrated that sodium butyrate (NaB) reduces hepatic steatosis, improving respiratory capacity and mitochondrial dysfunction in obese mice. Read More

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http://dx.doi.org/10.1096/fj.201900927RRDOI Listing
January 2020

Valproate and Retinoic Acid in Combination With Decitabine in Elderly Nonfit Patients With Acute Myeloid Leukemia: Results of a Multicenter, Randomized, 2 × 2, Phase II Trial.

J Clin Oncol 2020 01 3;38(3):257-270. Epub 2019 Dec 3.

University Hospital of Ulm, Ulm, Germany.

Purpose: DNA-hypomethylating agents are studied in combination with other epigenetic drugs, such as histone deacetylase inhibitors or differentiation inducers (eg, retinoids), in myeloid neoplasias. A randomized, phase II trial with a 2 × 2 factorial design was conducted to investigate the effects of the histone deacetylase inhibitor valproate and all- retinoic acid (ATRA) in treatment-naive elderly patients with acute myeloid leukemia (AML).

Patients And Methods: Two hundred patients (median age, 76 years; range, 61-92 years) ineligible for induction chemotherapy received decitabine (20 mg/m intravenously, days 1 to 5) alone (n = 47) or in combination with valproate (n = 57), ATRA (n = 46), or valproate + ATRA (n = 50). Read More

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http://dx.doi.org/10.1200/JCO.19.01053DOI Listing
January 2020

Development of a neural rosette formation assay (RoFA) to identify neurodevelopmental toxicants and to characterize their transcriptome disturbances.

Arch Toxicol 2020 01 11;94(1):151-171. Epub 2019 Nov 11.

In Vitro Toxicology and Biomedicine, Department Inaugurated By the Doerenkamp-Zbinden Chair Foundation, University of Konstanz, Box 657, 78457, Konstanz, Germany.

The first in vitro tests for developmental toxicity made use of rodent cells. Newer teratology tests, e.g. Read More

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http://dx.doi.org/10.1007/s00204-019-02612-5DOI Listing
January 2020

Unmet Quality Needs in Oral Drug Delivery: Contrasts of Drug Content and Uniformity on Distinct Approaches for Achieving Individual Dosing.

AAPS PharmSciTech 2019 Nov 8;20(8):332. Epub 2019 Nov 8.

Departamento de Psicobiologia, Universidade Federal de São Paulo, Rua Napoleão de Barros, 925, São Paulo, SP, 04024-002, Brazil.

Individualized dosing is often required in pharmacotherapy, particularly for pediatric and geriatric patients and adjustment of drugs that demand dose adaptation. This study aimed to evaluate critical quality attributes (CQAs) of doses obtained by distinct approaches for achieving individual dosing. Approaches were evaluated as follows: subdivision of tablets by splitter and hand (haloperidol) and delivery by plastic dropper bottle (haloperidol), glass dropper bottle (clonazepam), dosing cup (sodium valproate), and dosing syringe (carbamazepine), including brand name, generic, and similar marketed products. Read More

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http://dx.doi.org/10.1208/s12249-019-1546-1DOI Listing
November 2019

Systemic Metabolomic Profiling of Acute Myeloid Leukemia Patients before and During Disease-Stabilizing Treatment Based on All-Trans Retinoic Acid, Valproic Acid, and Low-Dose Chemotherapy.

Cells 2019 10 10;8(10). Epub 2019 Oct 10.

Department of Medicine, Haukeland University Hospital, 5021 Bergen, Norway.

Acute myeloid leukemia (AML) is an aggressive malignancy, and many elderly/unfit patients cannot receive intensive and potentially curative therapy. These patients receive low-toxicity disease-stabilizing treatment. The combination of all-trans retinoic acid (ATRA) and the histone deacetylase inhibitor valproic acid can stabilize the disease for a subset of such patients. Read More

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http://dx.doi.org/10.3390/cells8101229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829623PMC
October 2019
1 Read

Paternal valproic acid exposure in mice triggers behavioral alterations in offspring.

Neurotoxicol Teratol 2019 Nov - Dec;76:106837. Epub 2019 Oct 22.

Department of Chemical Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.

Sodium valproate (VPA) is the most widely used antiepileptic drug and is increasingly also being used for several non-epileptic indications including migraines and bipolar disorder. It is known that maternal VPA exposure during pregnancy increases the risk of autism spectrum disorder (ASD) in children. Animal model studies have shown that maternal treatment with VPA in rodents conveys an increased risk for ASD-like phenotypes at the molecular, cellular, and behavioral levels. Read More

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http://dx.doi.org/10.1016/j.ntt.2019.106837DOI Listing

Early polytherapy for benzodiazepine-refractory status epilepticus.

Epilepsy Behav 2019 12 18;101(Pt B):106367. Epub 2019 Oct 18.

Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Epilepsy Research Laboratory (151), Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA; Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Electronic address:

The transition from single seizures to status epilepticus (SE) is associated with malaptive trafficking of synaptic gamma-aminobutyric acid (GABA) and glutamate receptors. The receptor trafficking hypothesis proposes that these changes are key events in the development of pharmacoresistance to antiepileptic drugs (AEDs) during SE, and that blocking their expression will help control drug-refractory SE (RSE). We tested this hypothesis in a model of SE induced by very high-dose lithium and pilocarpine (RSE), and in a model of SE induced by sc soman. Read More

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http://dx.doi.org/10.1016/j.yebeh.2019.06.011DOI Listing
December 2019
1 Read

Association between the perturbation of bile acid homeostasis and valproic acid-induced hepatotoxicity.

Biochem Pharmacol 2019 12 16;170:113669. Epub 2019 Oct 16.

Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. Electronic address:

Valproic acid (VPA), a widely prescribed antiepileptic drug, is known to induce hepatotoxicity. However, the mechanisms underlying this toxicity are not well understood. In this study, we performed a nontargeted metabolomic analysis of children with epilepsy treated with VPA (n = 23). Read More

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http://dx.doi.org/10.1016/j.bcp.2019.113669DOI Listing
December 2019
1 Read

Melatonin ameliorates sodium valproate-induced hepatotoxicity in rats.

Mol Biol Rep 2020 Jan 17;47(1):317-325. Epub 2019 Oct 17.

Faculty of Medicine, Department of Physiology, Çanakkale Onsekiz Mart University, Çanakkale, Turkey.

Valproic acid (VPA) is a anticonvulsant and mood-stabilizing agent used to treat epilepsy in patients of all ages. However, it can cause hepatotoxicity with increased oxidative stress. Melatonin (MEL) is known as antioxidant and antiinflammatory agent. Read More

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http://dx.doi.org/10.1007/s11033-019-05134-6DOI Listing
January 2020

Use of meropenem to treat valproic acid overdose.

Am J Emerg Med 2019 11 4;37(11):2120.e5-2120.e7. Epub 2019 Sep 4.

Department of Pharmacy, Memorial Hermann The Woodlands Hospital, The Woodlands, TX 77380, United States of America.

Overdose of valproic acid (VPA) or its derivatives can cause significant toxicities such as hyperammonemia or altered mental status. While levocarnitine has been used historically to manage VPA-associated hyperammonemia, no standard of therapy exists to manage VPA toxicity. We present a case of VPA overdose managed with meropenem in addition to levocarnitine. Read More

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http://dx.doi.org/10.1016/j.ajem.2019.158426DOI Listing
November 2019
2 Reads

Rational polytherapy in the treatment of cholinergic seizures.

Neurobiol Dis 2020 01 24;133:104537. Epub 2019 Aug 24.

Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Epilepsy Research Laboratory (151), Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, USA; Brain Research Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA., USA. Electronic address:

The initiation and maintenance phases of cholinergic status epilepticus (SE) are associated with maladaptive trafficking of synaptic GABA and glutamate receptors. The resulting pharmacoresistance reflects a decrease in synaptic GABA receptors and increase in NMDA and AMPA receptors, which tilt the balance between inhibition and excitation in favor of the latter. If these changes are important to the pathophysiology of SE, both should be treated, and blocking their consequences should have therapeutic potential. Read More

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http://dx.doi.org/10.1016/j.nbd.2019.104537DOI Listing
January 2020
7 Reads

Prenatal exposure to valproic acid is associated with altered neurocognitive function and neurogenesis in the dentate gyrus of male offspring rats.

Brain Res 2019 11 22;1723:146403. Epub 2019 Aug 22.

Department of Psychiatry, Juntendo University, Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 1138431, Japan. Electronic address:

In pregnant women with epilepsy, it is imperative to balance the safety of the mother and the potential teratogenicity of anticonvulsants, which could cause impairments such as intellectual disability and cleft lip. In this study, we examined behavioral and hippocampal neurogenesis alterations in male offspring of rats exposed to valproic acid (VPA) during pregnancy. Pregnant Wistar rats received daily intraperitoneal injections of VPA (100 mg/kg/day or 200 mg/kg/day) from embryonic day 12. Read More

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http://dx.doi.org/10.1016/j.brainres.2019.146403DOI Listing
November 2019
3 Reads

Accuracy, discriminative properties and reliability of a human ESC-based in vitro toxicity assay to distinguish teratogens responsible for neural tube defects.

Arch Toxicol 2019 08 10;93(8):2375-2384. Epub 2019 Aug 10.

Reproductive Medicine and Gynaecological Endocrinology (RME), University Hospital, University of Basel, Vogesenstrasse 134, 4031, Basel, Switzerland.

The poor correlation of developmental toxicity studies in animals with human outcome data has emphasized the need for complementary assays based on human cells and tissues. As neural tube defects represent an important proportion of congenital malformations, we evaluated here the accuracy of a human embryonic stem cell (hESC)-based assay to predict chemically induced disruption of neural tube formation. As teratogenic compounds, we used cyclopamine (CPA), valproic acid (VPA), ochratoxin A (OTA) and mycophenolic acid (MMF), all suspected or known inducers of human neural tube defects, as well as theophylline and saccharin as negative control compounds. Read More

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http://dx.doi.org/10.1007/s00204-019-02512-8DOI Listing
August 2019
4 Reads

Lipidomic Profiling Reveals Disruption of Lipid Metabolism in Valproic Acid-Induced Hepatotoxicity.

Front Pharmacol 2019 19;10:819. Epub 2019 Jul 19.

Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, China.

Valproic acid (VPA) is one of the most widely prescribed antiepileptic drugs, as VPA-induced hepatotoxicity is one of the most severe adverse reaction that can lead to death. The objective of this study was to gain an understanding of dysregulated lipid metabolism in mechanism of hepatotoxicity. Nontargeted lipidomics analysis with liquid chromatography-quadrupole-time-of-flight mass spectrometry (LC-Q-TOF/MS) was performed to explore differential lipids from the patient serum and L02 cells. Read More

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http://dx.doi.org/10.3389/fphar.2019.00819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659130PMC
July 2019
4 Reads

The dual-active histamine H3 receptor antagonist and acetylcholine esterase inhibitor E100 ameliorates stereotyped repetitive behavior and neuroinflammmation in sodium valproate induced autism in mice.

Chem Biol Interact 2019 Oct 30;312:108775. Epub 2019 Jul 30.

Department of Pharmacology & Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, United Arab Emirates. Electronic address:

Postnatal exposure to valproic acid (VPA) in rodents induces autism-like neurobehavioral defects which are comparable to the motor and cognitive deficits observed in humans with autism spectrum disorder (ASD). Histamine H3 receptor (H3R) and acetylcholine esterase (AChE) are involved in several cognitive disorders such as Alzheimer's disease, schizophrenia, anxiety, and narcolepsy, all of which are comorbid with ASD. Therefore, the present study aimed at evaluating effect of the novel dual-active ligand E100 with high H3R antagonist affinity and balanced AChE inhibition on autistic-like repetitive behavior, anxiety parameters, locomotor activity, and neuroinflammation in a mouse model of VPA-induced ASD in C57BL/6 mice. Read More

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http://dx.doi.org/10.1016/j.cbi.2019.108775DOI Listing
October 2019
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Syntheses of Benzo[]Thiazol-2(3)-One Derivatives and Their Antidepressant and Anticonvulsant Effects.

Mar Drugs 2019 Jul 23;17(7). Epub 2019 Jul 23.

College of Medicine, Jiaxing University, Jiaxing 314001, China.

Thirty-four new benzo[]thiazol derivatives -, -, and - were synthesized and investigated for their potential antidepressant and anticonvulsant effects. In a forced swimming test, and showed the highest antidepressant and anticonvulsant effects. and displayed a higher percentage decrease in immobility duration (89. Read More

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http://dx.doi.org/10.3390/md17070430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669756PMC

Diagnosis and management of individuals with Fetal Valproate Spectrum Disorder; a consensus statement from the European Reference Network for Congenital Malformations and Intellectual Disability.

Orphanet J Rare Dis 2019 07 19;14(1):180. Epub 2019 Jul 19.

Clinical Genetics, Royal Devon and Exeter NHS Foundation Trust, Gladstone Rd, Exeter, UK.

Background: A pattern of major and minor congenital anomalies, facial dysmorphic features, and neurodevelopmental difficulties, including cognitive and social impairments has been reported in some children exposed to sodium valproate (VPA) during pregnancy. Recognition of the increased risks of in utero exposure to VPA for congenital malformations, and for the neurodevelopmental effects in particular, has taken many years but these are now acknowledged following the publication of the outcomes of several prospective studies and registries. As with other teratogens, exposure to VPA can have variable effects, ranging from a characteristic pattern of major malformations and significant intellectual disability to the other end of the continuum, characterised by facial dysmorphism which is often difficult to discern and a more moderate effect on neurodevelopment and general health. Read More

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http://dx.doi.org/10.1186/s13023-019-1064-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642533PMC
July 2019
9 Reads

A Time-Embedding Network Models the Ontogeny of 23 Hepatic Drug Metabolizing Enzymes.

Chem Res Toxicol 2019 08 29;32(8):1707-1721. Epub 2019 Jul 29.

Institute for Informatics , Washington University in St. Louis , Saint Louis , Missouri 63110 , United States.

Pediatric patients are at elevated risk of adverse drug reactions, and there is insufficient information on drug safety in children. Complicating risk assessment in children, there are numerous age-dependent changes in the absorption, distribution, metabolism, and elimination of drugs. A key contributor to age-dependent drug toxicity risk is the ontogeny of drug metabolism enzymes, the changes in both abundance and type throughout development from the fetal period through adulthood. Read More

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http://dx.doi.org/10.1021/acs.chemrestox.9b00223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933754PMC
August 2019
4 Reads
3.529 Impact Factor

Insights into Molecular Interactions of human Wnt5b and Frizzled proteins for their role in teratogenicity.

Bioinformation 2019 15;15(4):246-254. Epub 2019 Apr 15.

Toxicology and Computational Biology Group, Centre for Bioinformatics, M. D. University, Rohtak, Haryana 124001 India.

Wnt-Fzd signalling plays vital role in different physiological pathways including embryonic development and supposed to be probable target of many teratogens. The present study was done to investigate the role of human Wnt5b interaction with different isoforms of human Fzds and also the molecular interactions of their complexes with selected known teratogens [Carbamazepine (CBZ), Retinoic acid (RA), Valproic acid (VPA), Aminopterin (AMP) and Phenytoin (PHY)] using Niclosamide (NLM) as standard. The models of hWnt5b and hFzd isoforms, whose solved crystal structures were unavailable, were generated using homology modeling and hWnt5b was subjected to protein-protein docking studies against different isoforms of hFzd. Read More

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http://dx.doi.org/10.6026/97320630015246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599440PMC
April 2019
5 Reads

Study of Visual Function in Adult Epileptic Patients on Sodium Valproate or Carbamazepine Monotherapy.

Cureus 2019 Apr 27;11(4):e4553. Epub 2019 Apr 27.

Ophthalmology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, MYS.

Objective Epilepsy is a debilitating disease. Visual function changes have been reported and may be attributed to the epileptic changes or as a result of medication side effect. Sodium valproate and carbamazepine are both first line anti-epileptic medications used in Malaysian health care. Read More

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http://dx.doi.org/10.7759/cureus.4553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592832PMC
April 2019
4 Reads

Metronomic Chemotherapy for Children in Low- and Middle-Income Countries: Survey of Current Practices and Opinions of Pediatric Oncologists.

J Glob Oncol 2019 07;5:1-8

Assistance Publique-Hôpitaux de Marseille, La Timone Hospital, Marseille, France.

Purpose: Low- and middle-income countries (LMICs) experience the burden of 80% of new childhood cancer cases worldwide, with cure rates as low as 10% in some countries. Metronomics combines frequent administrations of low-dose chemotherapy with drug repurposing, which consists of using already-approved drugs for new medical applications. With wide availability, limited costs, and little infrastructure needs, metronomics can be part of constraint-adapted regimens in these resource-limited settings-with the understanding that metronomics shall not be a substitute for standard treatments when available and doable. Read More

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http://dx.doi.org/10.1200/JGO.18.00244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613668PMC
July 2019
11 Reads

Ameliorating impacts of ginseng on the apoptosis of spermatogenic cells and sperm quality in temporal lobe epilepsy rat model treated with valproate.

Andrologia 2019 Oct 26;51(9):e13348. Epub 2019 Jun 26.

Department of Anatomical Sciences, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.

Both epilepsy and valproate (VPA), as an antiepileptic drug, negatively affect male sexual function. The present study was conducted to evaluate the ameliorating impacts of ginseng on sperm quality, architecture of seminiferous epithelium and spermatogenic cell apoptosis in temporal lobe epilepsy (TLE) animal model treated with VPA. Fifty-six adult male rats were divided into seven groups including untreated control (Co), epilepsy (E), valproate (V), epilepsy-valproate (EV), epilepsy-ginseng (EG), valproate-ginseng (VG) and epilepsy-valproate-ginseng (EVG). Read More

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http://dx.doi.org/10.1111/and.13348DOI Listing
October 2019
3 Reads