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Tania E Perez Jimenez, Katrina L Mealey, Tamara L Grubb, Stephen A Greene, Michael H Court
Tramadol is widely used to manage mild to moderately painful conditions in dogs. However, this use is controversial since clinical efficacy studies in dogs showed conflicting results, while pharmacokinetic studies demonstrated relatively low circulating concentrations of O-desmethyltramadol (M1). Analgesia has been attributed to the opioid effects of M1, while tramadol and the other major metabolite (N-desmethyltramadol, M2) are considered inactive at opioid receptors. The aims of this study were to determine whether cytochrome P450 (CYP) dependent M1 formation by dog liver microsomes is slower compared with cat and human liver microsomes; and identify the CYPs responsible for M1 and M2 formation in canine liver...
October 6, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Yu Yan, Xin Cheng, Ren-Hao Yang, He Li, Jian-Long Chen, Zheng-Lai Ma, Guang Wang, Manli Chuai, Xuesong Yang
Phenobarbital is an antiepileptic drug that is widely used to treat epilepsy in a clinical setting. However, a long term of phenobarbital administration in pregnant women may produce side effects on embryonic skeletogenesis. In this study, we aim to investigate the mechanism by which phenobarbital treatment induces developmental defects in long bones. We first determined that phenobarbital treatment decreased chondrogenesis and inhibited the proliferation of chondrocytes in chick embryos. Phenobarbital treatment also suppressed mineralization in both in vivo and in vitro long bone models...
2016: Frontiers in Pharmacology
Ravali Alagandula, Xiang Zhou, Baochuan Guo
RATIONALE: LC-MS/MS is the gold standard of urine drug testing. However, current LC-based methods are time consuming, limiting the throughput of MS-based testing and increasing the cost. This is particularly problematic for quantification of drugs such as phenobarbital, which is often analyzed in a separate run because they must be negatively ionized. METHOD: This study examined the feasibility of using a dilute and shoot-flow injection method without LC separation to quantify drugs with phenobarbital as a model system...
October 14, 2016: Rapid Communications in Mass Spectrometry: RCM
S Mücke, M Nagel, J P Siedentopf, C Bührer, D Hüseman
Background: Infants exposed to opiates antenatally display withdrawal symptoms after birth referred to as neonatal abstinence syndrome (NAS). Patients: A total of 366 newborns (166 females, 10 twins) from 361 mothers were diagnosed with NAS from 2000 to 2011 at a single large metropolitan referral center. Methods: Retrospective chart review of all newborn infants exposed to opiates in utero. Results: 20% were premature (gestational age<37 weeks), 32% were small-for-gestational-age (<10(th) percentile)...
October 10, 2016: Klinische Pädiatrie
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
Beth Williamson, Mathias Lorbeer, Michael D Mitchell, Timothy G Brayman, Robert J Riley
The nuclear pregnane X receptor (PXR) regulates the expression of genes involved in the metabolism, hepatobiliary disposition, and toxicity of drugs and endogenous compounds. PXR is a promiscuous nuclear hormone receptor (NHR) with significant ligand and DNA-binding crosstalk with the constitutive androstane receptor (CAR); hence, defining the precise role of PXR in gene regulation is challenging. Here, utilising a novel PXR-knockout (KO) HepaRG cell line, real-time PCR analysis was conducted to determine PXR involvement for a range of inducers...
October 2016: Pharmacology Research & Perspectives
Mindl M Messinger, Kimberly L Dinh, Erin J McDade, Brady S Moffett, Angus A Wilfong, Antonio G Cabrera
BACKGROUND: Advances in cardiac operations over the last few decades, including corrective operations in early life, have dramatically increased the survival of children with congenital heart disease. However, postoperative care has been associated with neurologic complications, with seizures being the most common manifestation. The primary objective of this study is to describe the outcomes in pediatric patients who received an antiepileptic drug (AED) post-cardiac surgery. METHOD: A retrospective cohort study was performed in all patients less than 18 years of age who received an AED in the cardiovascular intensive care unit at Texas Children's Hospital from June 2002 until June 2012...
July 2016: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
Christopher R Newey, Dolora Wisco, Premkumar Nattanmai, Aarti Sarwal
BACKGROUND: Refractory status epilepticus is often treated with third-line therapy, such as pentobarbital coma. However, its use is limited by side effects. Recognizing and preventing major and minor adverse effects of prolonged pentobarbital coma may increase good outcomes. This study retrospectively reviewed direct and indirect medical and surgical pentobarbital coma. METHODS: Retrospective chart review of all patients with refractory status epilepticus treated with pentobarbital over a 1 year period at a large tertiary care center...
October 2016: Therapeutic Advances in Drug Safety
Nicola Groll, Tamara Petrikat, Silvia Vetter, Christine Wenz, Joern Dengjel, Christine Gretzmeier, Frederik Weiss, Oliver Poetz, Thomas O Joos, Michael Schwarz, Albert Braeuning
The antiepileptic drug phenobarbital (PB) exerts hepatic effect based on indirect activation of the constitutive androstane receptor (CAR) via inhibition of the epidermal growth factor receptor (EGFR) and the kinase Src. It has furthermore been observed that in mice PB suppresses the growth of hepatocellular carcinoma with overactive signaling through the oncogenic Wnt/β-catenin pathway, thus suggesting an interference of PB with β-catenin signaling. The present work was aimed to characterize effects of PB on β-catenin signaling at different cellular levels and to elucidate molecular details of the interaction of PB and β-catenin in an in vitro system of mouse hepatoma cells...
September 30, 2016: Toxicology
B J Hughes, J Thomas, A M Lynch, S J Borghoff, S Green, T Mensing, S S Sarang, M J LeBaron
In a National Toxicology Program (NTP) chronic inhalation study with methyl isobutyl ketone (MIBK), increases in hepatocellular adenomas and hepatocellular adenomas and carcinomas (combined) were observed in male and female B6C3F1 mice at 1800 ppm. A DNA reactive Mode-of-Action (MOA) for this liver tumor response is not supported by the evidence as MIBK and its major metabolites lack genotoxicity in both in vitro and in vivo studies. Constitutive androstane receptor (CAR) nuclear receptor-mediated activation has been hypothesized as the MOA for MIBK-induced mouse liver tumorigenesis...
September 21, 2016: Regulatory Toxicology and Pharmacology: RTP
Rita Citraro, Emilio Russo, Antonio Leo, Roberto Russo, Carmen Avagliano, Michele Navarra, Antonio Calignano, Giovambattista De Sarro
We evaluated the effects of ACEA (selective cannabinoid (CB)1 receptor agonist), WIN 55,212-2 mesylate (WIN; non-selective CB1 and CB2 receptor agonist) and N-palmitoylethanolamine (PEA; an endogenous fatty acid of ethanolamide) in DBA/2 mice, a genetic model of reflex audiogenic epilepsy. PEA, ACEA or WIN intraperitoneal (i.p.) administration decreased the severity of tonic-clonic seizures. We also studied the effects of PEA, WIN or ACEA after co-administration with NIDA-41020 (CB1 receptor antagonist) or GW6471 (PPAR-α antagonist) and compared the effects of WIN, ACEA and PEA in order to clarify their mechanisms of action...
September 20, 2016: European Journal of Pharmacology
Selvakumar Palanisamy, Balamurugan Thirumalraj, Shen-Ming Chen, Yi-Ting Wang, Vijayalakshmi Velusamy, Sayee Kannan Ramaraj
We report a novel and sensitive amperometric sensor for chlorpromazine (CPZ) based on reduced graphene oxide (RGO) and polydopamine (PDA) composite modified glassy carbon electrode. The RGO@PDA composite was prepared by electrochemical reduction of graphene oxide (GO) with PDA. The RGO@PDA composite modified electrode shows an excellent electro-oxidation behavior to CPZ when compared with other modified electrodes such as GO, RGO and GO@PDA. Amperometric i-t method was used for the determination of CPZ. Amperometry result shows that the RGO@PDA composite detects CPZ in a linear range from 0...
2016: Scientific Reports
Rani Ameena Bashir, Liza Espinoza, Sakeer Vayalthrikkovil, Jeffrey Buchhalter, Leigh Irvine, Luis Bello-Espinosa, Khorshid Mohammad
BACKGROUND: We report the impact of implementing continuous video electroencephalography monitoring for neonates with hypoxic-ischemic encephalopathy via a protocol in the context of neonatal neuro-critical care program. METHODS: Neonates with hypoxic-ischemic encephalopathy were studied retrospectively two years before and after implementing continuous video electroencephalography for 72 hours as a care protocol. Before continuous video electroencephalography, a 60-minute routine electroencephalography was performed at the discretion of the provider...
August 3, 2016: Pediatric Neurology
Iwona Zarnowska, Jarogniew J Luszczki, Tomasz Zarnowski, Piotr Wlaz, Stanislaw J Czuczwar, Maciej Gasior
Among non-pharmacological treatments, the ketogenic diet (KD) has the strongest demonstrated evidence of clinical success in drug resistant epilepsy. In an attempt to model the anticonvulsant effects of the KD pre-clinically, the present study assessed the effects of the KD against electroshock-induced convulsions in mice. After confirming that exposure to the KD for 2 weeks resulted in stable ketosis and hypoglycemia, mice were exposed to electroshocks of various intensities to establish general seizure susceptibility...
September 20, 2016: Metabolic Brain Disease
Christopher McPherson
Neonatal abstinence syndrome (NAS) from in utero opioid exposure has reached epidemic levels in the United States. Although nonpharmacologic therapies form the foundation of care, many neonates require pharmacotherapy. Morphine represents the most widely used first-line agent and effectively treats the symptoms of withdrawal. However, methadone or buprenorphine may facilitate earlier discharge. Although phenobarbital is traditionally used when opioids fail, clonidine may be a more appropriate adjunctive agent to minimize negative neurodevelopmental impact...
2016: Neonatal Network: NN
Roberto Michelucci, Elena Pasini, Patrizia Riguzzi, Eva Andermann, Reetta Kälviäinen, Pierre Genton
Generalized motor seizures, usually tonic-clonic, tonic-vibratory, myoclonic or clonic, and stimulus-sensitive/action myoclonus are typical features of progressive myoclonus epilepsies (PMEs). Despite the introduction of many anticonvulsants, the treatment of these symptoms, particularly myoclonus, remains challenging, due to the incomplete and often transitory effects of most drugs. Moreover, treatment is only symptomatic, since therapy targeting the underlying aetiology for these genetic conditions is in its infancy...
September 1, 2016: Epileptic Disorders: International Epilepsy Journal with Videotape
Nan Shu, Mengyue Hu, Zhaoli Ling, Peihua Liu, Fan Wang, Ping Xu, Zeyu Zhong, Binbin Sun, Mian Zhang, Feng Li, Qiushi Xie, Xiaodong Liu, Li Liu
Liver injury is a common adverse effect of atorvastatin. This study aimed to investigate atorvastatin-induced hepatotoxicity in diabetic rats induced by high-fat diet combined with streptozotocin. The results showed that 40 mg/kg atorvastatin was lethal to diabetic rats, whose mean survival time was 6.2 days. Severe liver injury also occurred in diabetic rats treated with 10 mg/kg and 20 mg/kg atorvastatin. The in vitro results indicated that atorvastatin cytotoxicity in hepatocytes of diabetic rats was more severe than normal and high-fat diet feeding rats...
2016: Scientific Reports
Sierk Haenisch, Eva-Lotta von Rüden, Hannes Wahmkow, Maruja L Rettenbeck, Christina Michler, Vera Russmann, Henrike Bruckmueller, Vicki Waetzig, Ingolf Cascorbi, Heidrun Potschka
Regulatory RNAs play a key role in the regulation of protein expression patterns in neurological diseases. Here we studied the regulation of miRNAs in a chronic rat model of temporal lobe epilepsy. The analysis was focused on a putative link with pharmacoresponsiveness as well as the functional implications of the regulation of a selected miRNA. The findings did not reveal a difference in hippocampal miRNA expression between phenobarbital responders and non-responders. However, when comparing rats following status epilepticus with control rats we identified 13 differentially expressed miRNAs with miRNA-187-3p being most strongly regulated...
September 8, 2016: ACS Chemical Neuroscience
Abolfazl Khoshdel, Hajar Noormohammadi, Soleiman Kheiri, Roya Reisi, Seyed Mohammad-Kazem Nourbakhsh, Gholam Reza Panahandeh, Esfandiar Heidarian
OBJECTIVES: Perinatal asphyxia (PA) is very significant in perinatal medicine due to the involvement of the central nervous system. This study was conducted to investigate the biochemical, clinical, and paraclinical changes associated with phenobarbital administration in neonates with PA. METHODS: In this prospective, case-control study, 30 neonates with PA in two groups of 15 each (case and control) were investigated. The case group received 20 mg/kg intravenous phenobarbital within six hours of birth, and the control group did not receive phenobarbital...
September 2016: Oman Medical Journal
Francesca Tomaciello, Karine Leclercq, Rafal M Kaminski
Resveratrol (3,4',5-stilbenetriol) is a natural product having diverse anti-inflammatory and antioxidant properties. The compound has a wide spectrum of pharmacological and metabolic activity, including cardioprotective, neuroprotective, anticarcinogenic and anti-aging effects reported in numerous studies. Some reports also suggest potential anticonvulsant properties of resveratrol. In the present study, we used in mice three different seizure models which are routinely applied in preclinical drug discovery...
October 6, 2016: Neuroscience Letters
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