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https://www.readbyqxmd.com/read/28331645/propylene-glycol-toxicity-in-adolescent-with-refractory-myoclonic-status-epilepticus
#1
Kara A Bjur, Bryan C Cannon, Anthony L Fine, Matthew J Ritter, Kerry E Schueler, Michael E Nemergut
Propylene glycol (PG) is a solvent commonly used in medications that, while benign at low doses, may cause toxicity in adults and children at high doses. We describe a case and the physiologic sequelae of propylene glycol toxicity manifested in a critically ill adolescent male with refractory myoclonic status epilepticus aggressively treated with multiple PG-containing medications (lorazepam, phenobarbital, and pentobarbital)-all within accepted dosing guidelines and a total daily PG exposure previously recognized to be safe...
2017: Case Reports in Pediatrics
https://www.readbyqxmd.com/read/28328763/induration-at-injection-or-infusion-site-may-reduce-bioavailability-of-parenteral-phenobarbital-administration
#2
Hirokazu Nakayama, Hirotoshi Echizen, Ryuichi Ogawa, Atsuya Akabane, Toshiaki Kato, Takao Orii
BACKGROUND: Phenobarbital is well tolerated and effective for controlling agitation or preventing convulsion at the end of life. No information is available concerning parenteral bioavailability of phenobarbital when induration develops at injection or infusion site. We investigated whether induration at injection or infusion site is related to phenobarbital bioavailability via parenteral routes of continuous subcutaneous infusion and intermittent subcutaneous or intramuscular injection...
March 21, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28315722/risk-mitigation-for-children-exposed-to-drugs-during-gestation-a-critical-role-for-animal-preclinical-behavioral-testing
#3
REVIEW
Irving Zucker
Many drugs with unknown safety profiles are administered to pregnant women, placing their offspring at risk. I assessed whether behavioral outcomes for children exposed during gestation to antidepressants, anxiolytics, anti-seizure, analgesic, anti-nausea and sedative medications can be predicted by more extensive animal studies than are part of the FDA approval process. Human plus rodent data were available for only 8 of 33 CNS-active drugs examined. Similar behavioral and cognitive deficits, including autism and ADHD emerged in human offspring and in animal models of these disorders after exposure to fluoxetine, valproic acid, carbamazepine, phenytoin, phenobarbital and acetaminophen...
March 16, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28298240/interstrain-differences-in-the-expression-and-activity-of-cyp2a5-in-the-mouse-liver
#4
Katia S Poça, Thiago E M Parente, Lucas F Chagas, Bruna S Leal, Hellen S Leal, Francisco J R Paumgartten, Ana C A X De-Oliveira
BACKGROUND: Cytochrome P450 2A5 (Cyp2a5), a mouse enzyme orthologous of human CYP2A6, catalyzes a number of toxicologically important reactions, including the metabolism of nicotine, aflatoxin B1, and several other xeno- and endobiotics. Cyp2a5 expression is complex and not yet fully understood. We investigated inter-strain differences in the activity and mRNA expression of hepatic Cyp2a5. Cyp1a1/2 and Cyp2b9/10 activities were evaluated for comparative purposes. Data on the interstrain differences in the expression and activity of Cyp2a5 are important to select a suitable mouse model for studying CYP2A6-mediated metabolism...
March 15, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28290134/animal-models-of-seizures-and-epilepsy-past-present-and-future-role-for-the-discovery-of-antiseizure-drugs
#5
Wolfgang Löscher
The identification of potential therapeutic agents for the treatment of epilepsy requires the use of seizure models. Except for some early treatments, including bromides and phenobarbital, the antiseizure activity of all clinically used drugs was, for the most part, defined by acute seizure models in rodents using the maximal electroshock and subcutaneous pentylenetetrazole seizure tests and the electrically kindled rat. Unfortunately, the clinical evidence to date would suggest that none of these models, albeit useful, are likely to identify those therapeutics that will effectively manage patients with drug resistant seizures...
March 13, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28287069/ictus-emeticus-presenting-as-an-unusual-seizure-type-in-chromosome-22q11-2-deletion-syndrome
#6
Pi-Lien Hung, Li-Tung Huang, Shang-Yeong Kwan, Kai-Ping Chang, Hsin-Hung Chen, Yi-Yen Lee, Hueng-Chuen Fan, Chien Chen
We present a case study of a patient with chromosome 22q11.2 deletion syndrome presenting with ictus emeticus, together with a review of the relevant literature. The patient developed generalized tonic-clonic seizures at 3 months old, and seizures eventually remitted after calcium therapy. He then experienced vigorous vomiting that occurred during sleep, with glassy eyes and legs flexion. Video-EEG recordings exhibited a switch in background activity from organized reactivity during normal sleep to left lateralized temporal delta activity, which was bilaterally synchronized during an emetic attack...
March 8, 2017: Epileptic Disorders: International Epilepsy Journal with Videotape
https://www.readbyqxmd.com/read/28281491/status-epilepticus-refractory-and-super-refractory
#7
REVIEW
Deepanshu Dubey, Jayantee Kalita, Usha K Misra
Status epilepticus (SE) is an important neurological emergency. It is defined as seizures lasting for 5 minutes or more or recurrent seizures without recovery of consciousness to baseline between the attacks. Refractory SE (RSE) is defined as SE persisting despite sufficient dose of benzodiazepines and at least one antiepileptic drug (AED), irrespective of time. Super refractory SE (SRSE) is defined as SE that continues for 24 hours or more after the use of anesthetic therapy, including cases that recur on weaning of the anesthestic agent...
2017: Neurology India
https://www.readbyqxmd.com/read/28280887/brivaracetam-population-pharmacokinetics-in-children-with-epilepsy-aged-1%C3%A2-month-to-16%C3%A2-years
#8
Rik Schoemaker, Janet R Wade, Armel Stockis
PURPOSE: The aims of the study were to develop a population pharmacokinetic model of orally administered brivaracetam in paediatric patients and to provide dosing suggestions. METHODS: Analysis included 600 brivaracetam plasma concentrations from a phase 2a study (NCT00422422; N01263) in 96 paediatric patients with epilepsy aged 1 month to 16 years, taking one to three concomitant antiepileptic drugs (AEDs). Pharmacokinetic analysis was performed using non-linear mixed effects modelling, and a stepwise covariate search was used to determine factors influencing brivaracetam clearance...
March 9, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28267983/synthesis-molecular-modeling-studies-and-anticonvulsant-activity-of-certain-1-benzyl-aryl-amino-cyclohexyl-methyl-esters
#9
Walaa Hamada Abd-Allah, Mona Elsayed Aboutabl, Mohamed Nabil Aboul-Enein, Aida Abdel Sattar El-Azzouny
A series of (1-(benzyl (aryl) amino) cyclohexyl) methyl esters 7a-n were prepared and screened for their anticonvulsant profile. Screening of these esters 7a-n and their starting alcohols 6a and 6b revealed that compound 7k was the most potent one in the scPTZ screening test with an ED50 value of 0.0056mmol/kg being about 10- and 164-fold more potent than phenobarbital (ED50=0.056mmol/kg) and ethosuximide (ED50=0.92mmol/kg) as reference drugs, respectively. Meanwhile, in the MES test, compounds 7b and 7k at doses 0...
February 27, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28267557/investigation-of-the-mechanism-of-triclosan-induced-mouse-liver-tumors
#10
Zemin Wang, Xilin Li, James E Klaunig
Chronic dietary exposure to Triclosan (TCS) produced increased incidence of liver tumors in mice. The mechanism for liver tumor induction has been attributed to activation of either peroxisome proliferator activated receptor α (PPARα) or constitutive androstane receptor (CAR). To further define the mechanism of TCS induced liver tumors, male CD-1 and C57BL/6 mice were treated with TCS at 0, 10, 100 and 200 mg/kg diet/day for 14 or 28 days. In addition, a recovery group and positive control groups for CAR or PPARα activation with either phenobarbital or diethylhexyl-phthalate were included in the 14-day study...
March 4, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28265001/phosphorylated-nuclear-receptor-car-forms-a-homodimer-to-repress-its-constitutive-activity-for-ligand-activation
#11
Ryota Shizu, Makoto Osabe, Lalith Perera, Rick Moore, Tatsuya Sueyoshi, Masahiko Negishi
Nuclear receptor CAR (NR1I3) regulates hepatic drug and energy metabolism as well as cell fate. Its activation can be a critical factor in drug-induced toxicity and disease development such as diabetes and tumors. CAR inactivates its constitutive activity by phosphorylation at threonine 38. Utilizing receptor for protein kinase 1 (RACK1) as the regulatory subunit, protein phosphatase PP2A dephosphorylates threonine 38 to activate CAR. Here we have demonstrated that CAR undergoes its homodimer-monomer conversion to regulate this dephosphorylation...
March 6, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28259126/10-6-plastoquinonyl-decyltriphenylphosphonium-skq1-does-not-increase-the-level-of-cytochromes-p450-in-rat-liver-and-human-hepatocyte-cell-culture
#12
K N Myasoedova, D N Silachev, A D Petrov
Mitochondria-targeted antioxidant SkQ1 did not increase the content of cytochromes P450 in livers of rats that were given SkQ1 in drinking water for 5 days in a dose (2.5 µmol per kg body weight) that exceeded 10 times the SkQ1 therapeutic dose. SkQ1 did not affect the levels of cytochrome P450 forms CYP1A2, CYP2B6, and CYP3A4 in monolayer cultures of freshly isolated human hepatocytes, while specific inducers of these forms (omeprazole, phenobarbital, and rifampicin, respectively) significantly increased expression of the cytochromes P450 under the same conditions...
December 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28254201/unusual-association-of-scn2a-epileptic-encephalopathy-with-severe-cortical-dysplasia-detected-by-prenatal-mri
#13
Silvia Bernardo, Enrica Marchionni, Sabrina Prudente, Paola De Liso, Alberto Spalice, Antonella Giancotti, Lucia Manganaro, Antonio Pizzuti
We present an atypical association of SCN2A epileptic encephalopathy with severe cortical dysplasia. SCN2A mutations are associated with epileptic syndromes from benign to extremely severe in absence of such macroscopic brain findings. Prenatal MRI (Magnetic Resonance Imaging) in a 32 weeks fetus, with US (Ultrasonography) diagnosis of isolated ventriculomegaly showed CNS (Central Nervous System) dysplasia characterized by lack of differentiation between cortical and subcortical layers, pachygyria and corpus callosum dysgenesis...
February 7, 2017: European Journal of Paediatric Neurology: EJPN
https://www.readbyqxmd.com/read/28245158/alternative-multiorgan-initiation-promotion-assay-for-chemical-carcinogenesis-in-the-wistar-rat
#14
Marize de Lourdes Marzo Solano, Noeme Souza Rocha, Luis Fernando Barbisan, Carla Adriene da Silva Franchi, Ana Lúcia Tozzi Spinardi-Barbisan, Maria Luiza Cotrim Sartor de Oliveira, Daisy Maria Fávero Salvadori, Lúcia Regina Ribeiro, João Lauro Viana de Camargo
The medium-term multiorgan initiation-promotion chemical bioassay (diethylnitrosamine, methyl-nitrosourea, butyl-hydroxybutylnitrosamine, dihydroxypropylnitrosamine, dimethylhydrazine [DMBDD]) with the Fischer 344 rat was proposed as an alternative to the conventional 2-year carcinogenesis bioassay for regulatory purposes. The acronym DMBDD stands for the names of five genotoxic agents used for initiation of multiorgan carcinogenesis. The Brazilian Agency for the Environment officially recognized a variation of this assay (DMBDD(b)) as a valid method to assess the carcinogenic potential of agrochemicals...
December 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/28237319/epilepsy-treatment-in-adults-and-adolescents-expert-opinion-2016
#15
REVIEW
Jerry J Shih, Julia B Whitlock, Nicole Chimato, Emily Vargas, Steven C Karceski, Ryan D Frank
INTRODUCTION: There are over twenty anti-seizure medications and anti-seizure devices available commercially in the United States. The multitude of treatment options for seizures can present a challenge to clinicians, especially those who are not subspecialists in the epilepsy field. Many clinical questions are not adequately answered in double-blind randomized controlled studies. In the presence of a knowledge gap, many clinicians consult a respected colleague with acknowledged expertise in the field...
February 22, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28235604/mir-466b-1-3p-regulates-p-glycoprotein-expression-in-rat-cerebral-microvascular-endothelial-cells
#16
Xiaobo Yang, Weimin Ren, Yiye Shao, Yinghui Chen
Epilepsy is one of the most common neurological disorders, and approximately one-third of epilepsy cases are resistant to treatment with anti-epileptic drug (AED). P-glycoprotein (P-gp) is a multi-drug transporter that is thought to play a pivotal role in multiple drug resistance (MDR) in epilepsy. The regulatory mechanism of P-gp remains largely unknown; however, recent studies have demonstrated that microRNAs (miRNAs) may regulate the chemo-resistance mediated by P-gp. This study investigated the effect of specific miRNAs that regulate P-gp expression in rat cerebral microvascular endothelial cells (RCMECs)...
February 22, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28218408/toxaphene-induced-mouse-liver-tumorigenesis-is-mediated-by-the-constitutive-androstane-receptor
#17
Zemin Wang, Xilin Li, Qiangen Wu, James C Lamb, James E Klaunig
Toxaphene was shown to increase liver tumor incidence in B6C3F1 mice following chronic dietary exposure. Preliminary evidence supported a role for the constitutive androstane receptor (CAR) in the mode of action of toxaphene-induced mouse liver tumors. However, these results could not rule out a role for the pregnane X receptor (PXR) in liver tumor formation. To define further the nuclear receptors involved in this study, we utilized CAR, PXR and PXR/CAR knockout mice (CAR(-/-) , PXR(-/-) and PXR(-/-) /CAR(-/-) ) along with the wild-type C57BL/6...
February 20, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28215634/isolation-and-expansion-of-human-pluripotent-stem-cell-derived-hepatic-progenitor-cells-by-growth-factor-defined-serum-free-culture-conditions
#18
Takayuki Fukuda, Kazuo Takayama, Mitsuhi Hirata, Yu-Jung Liu, Kana Yanagihara, Mika Suga, Hiroyuki Mizuguchi, Miho K Furue
Limited growth potential, narrow ranges of sources, and difference in variability and functions from batch to batch of primary hepatocytes cause a problem for predicting drug-induced hepatotoxicity during drug development. Human pluripotent stem cell (hPSC)-derived hepatocyte-like cells in vitro are expected as a tool for predicting drug-induced hepatotoxicity. Several studies have already reported efficient methods for differentiating hPSCs into hepatocyte-like cells, however its differentiation process is time-consuming, labor-intensive, cost-intensive, and unstable...
March 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28213422/phenobarbital-a-beneficial-eight-hourly-dosing-option
#19
Annette Wessmann
No abstract text is available yet for this article.
February 18, 2017: Veterinary Record
https://www.readbyqxmd.com/read/28190495/phenobarbital-or-potassium-bromide-as-an-add-on-antiepileptic-drug-for-the-management-of-canine-idiopathic-epilepsy-refractory-to-imepitoin
#20
E Royaux, L Van Ham, B J G Broeckx, I Van Soens, I Gielen, D Deforce, S F M Bhatti
Imepitoin has recently been approved in Europe for the management of dogs with idiopathic epilepsy. Currently, there is no evidence-based information available on the efficacy of antiepileptic drugs used as additions to the therapeutic regimen in dogs with idiopathic epilepsy that are not well controlled with imepitoin. The goal of this study was to evaluate the efficacy of phenobarbital or potassium bromide (KBr) as add-on antiepileptic drugs for controlling dogs refractory to a maximum dose of imepitoin (30 mg/kg twice daily)...
February 2017: Veterinary Journal
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