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Front Neurol 2020 6;11:95. Epub 2020 Mar 6.

Department of Neurosurgery, Skane University Hospital, Lund, Sweden.

Traumatic brain injury (TBI) constitutes a global epidemic. Overall outcome is poor, with mortality ranging from 10 to 70% and significant long-term morbidity. Several experimental reports have claimed effect on traumatic edema, but all clinical trials have failed. Read More

Am J Emerg Med 2020 Jan 8. Epub 2020 Jan 8.

Division of Medical Toxicology, Department of Emergency Medicine, University of Pittsburgh School of Medicine, USA; Pittsburgh Poison Center, Pittsburgh, PA, USA.

Background: Local anesthetic systemic toxicity characteristically occurs after inadvertent intravascular injection of local anesthetics; however, it is unclear if similar symptoms arise after intrathecal adminstration. Intrathecal use of local anesthetics for chronic pain is increasing and carries a potential risk of toxicity. Experience with the presenting symptoms and appropriate treatment for intrathecal local anesthetic toxicity is limited. Read More

Cell Mol Biol (Noisy-le-grand) 2019 Sep 30;65(7):99-104. Epub 2019 Sep 30.

Department of Orthopedics, The First Affiliated Hospital of Sun Yat-sen University, China.

Inflammation and insomnia are medical problems that may severely affect work and health, thereby necessitating strategies for their effective treatment. Icartin (ICT) is a major active monomeric component of icariin  . Studies have revealed that ICT possesses several pharmacological properties such anti-inflammatory, anti-tumor, anti-fibrotic, anti-osteoporotic and neuroprotective effects. Read More

Microbiol Immunol 2020 Jan 7;64(1):10-22. Epub 2019 Nov 7.

Division of Bioscience and Bioindustry, Graduate School of Technology, Industrial and Social Sciences, Tokushima University, Tokushima, Tokushima, Japan.

Streptolysin O (SLO) is a bacterial pore-forming toxin that is employed to permeabilize cell membranes in some biological experiments. SLO forms various types of pores with different shapes, increasing membrane ion permeability and subsequently inducing changes in membrane potential. To characterize the pores formed by SLO, the changes in membrane potential induced by SLO in rat lymphocytes were considered using flow cytometry with a voltage-sensitive fluorescent probe, bis-(1,3-dibutylbarbituric acid)trimethine oxonol (Oxonol). Read More

J Toxicol Sci 2019 ;44(7):459-469

Laboratory of Animal Reproductive Physiology, Graduate School of Environmental and Life Science, Okayama University.

Phenobarbital (PB) and Di (2-ethylhexyl) phthalate (DEHP), an anti-epileptic drug and a plasticizer used in flexible polyvinylchloride formulations, respectively, are well-known typical hepatotoxicants. This study investigated the effects of PB (100 mg/kg/day) or DEHP (500 mg/kg/day) on the endocrine system in intact juvenile/peripubertal male rats exposed for 31 days beginning on postnatal day 23. Slight hormone level changes, histopathological changes in thyroid gland or induction of UDP-glucuronosyltransferase in liver were observed in both the PB and DEHP groups. Read More

Animal 2020 Jan 26;14(1):129-137. Epub 2019 Jun 26.

Consultant Animal Welfare Science and Practice, Tulip House, 70 Borough High Street London Bridge, London SE1 1XF, UK.

Low atmospheric pressure stunning (LAPS) is a novel approach to pre-slaughter stunning of chickens using progressive hypobaric hypoxia by the application of gradual decompression (280s cycle) according to a set of prescribed pressure curves. Low atmospheric pressure stunning produces a non-recovery state. Concerns have been raised relating to the possible pathological and welfare consequences of expansion of air in the body during LAPS. Read More

Molecules 2019 Jun 8;24(11). Epub 2019 Jun 8.

School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Panyu District, Guangzhou 510006, Guangdong, China.

Celastrol and triptolide, as the two main bio-activity ingredients in have wide anticancer pharmacological potency, as well as anti-inflammatory and immunosuppression effects. However, they have potential hepatotoxicity and underlying mechanisms of them-induced toxicity mediated by hepatic CYP450s have not been well delineated. In the present study, we accessed the toxic effects and possible mechanism of celastrol and triptolide on primary rat hepatocytes. Read More

PLoS One 2019 29;14(5):e0217009. Epub 2019 May 29.

Laboratory of Vaccine & Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.

Researchers investigating cancer chemotherapy and management continue to search for agents that selectively kill malignant cells and leave healthy neighboring cells intact. Natural products provide relevant resources for anti-cancer drug discovery. However, the physicochemical properties of these compounds limit their efficient uptake and bioavailability. Read More

Cell Mol Biol (Noisy-le-grand) 2019 Apr 30;65(4):69-75. Epub 2019 Apr 30.

Department of Pain, Ganzhou People's Hospital, Ganzhou City, China.

Objective of this study was to investigate the sedative and hypnotic effects of palmatine and to observe whether its mechanism is related to 5-hydroxytryptamine (5-HT) and GABA. The sedative and hypnotic effects of palmatine on mice were observed with mouse autonomic activity test, direct sleep test, pentobarbital sodium in suprathreshold and subthreshold dose sleep test. The content of GABA and 5-HT in brain homogenate was determined by ELISA  method. Read More

J Toxicol Sci 2019 ;44(3):145-153

Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd.

A high incidence of positive results is obtained with in vitro genotoxicity tests, which do not correlate with the in vivo negative results in many cases. To address this issue, the metabolic profile of rat liver 9000 × g supernatant fraction (S9) pretreated with phenobarbital (PB) and 5,6-benzoflavone (BNF) was characterized. Furthermore, the in vitro micronucleus tests of 10 compounds were performed with PB-BNF-induced rat S9. Read More

Biol Pharm Bull 2019 ;42(3):501-506

Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University.

The mechanism underlying the increased pharmacological effects of phenobarbital in rats with glycerol-induced acute renal failure (ARF) was examined. In the experiments, a surgical cannula was inserted in the lateral ventricle of the rats for phenobarbital infusion, and the ARF induction was performed by intramuscular administration of 50% glycerol. The onset time of anesthesia by phenobarbital was determined with the tail flick method. Read More

Ther Drug Monit 2019 06;41(3):257-260

Pediatrics, PGIMER, Chandigarh, India.

Background: Phenobarbitone is frequently used for the treatment of seizures in neonates, but it has a narrow therapeutic index.

Case Presentation: A 28-week preterm infant born of vaginal delivery developed signs and symptoms suggestive of ventriculitis on day 9. After an episode of clonic seizures on day 11, phenobarbitone was administered intravenously at a loading dose of 20 mg/kg followed by maintenance doses of 6 mg/kg per day in 2 divided doses for 5 days. Read More

Eur J Pharm Sci 2019 Mar 23;130:124-136. Epub 2019 Jan 23.

Biomedical Sciences Program, Zewail City of Science and Technology, 12578 Cairo, Egypt. Electronic address:

A series of twenty five new thiobarbituric acid derivatives, viz. 3a-h, 4-7, 8a-c, 9, 10a-c, 11 and 12a-d, were designed and synthesized as potential cytotoxic agents. In-vitro screening of the new compounds against the three human cancer cell lines Caco-2, HepG-2 and MCF-7 was performed to assess their intrinsic activity. Read More

Bioorg Chem 2019 04 13;85:168-178. Epub 2018 Dec 13.

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Wuya College of Innovation, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

Despite the increasing need of new antituberculosis drugs, the number of agents approved for the market has fallen to an all-time low. In response to the emerging drug resistance followed, structurally unique chemical entities will be highlighted. decaprenylphosphoryl-β-d-ribose oxidase (DprE1) participating in the biosynthesis of mycobacterium cell wall is a highly vulnerable and validated antituberculosis target. Read More

Epilepsia 2019 02 7;60(2):315-321. Epub 2019 Jan 7.

Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.

Objectives: Children and adults are likely to be among the casualties in a civilian nerve agent exposure. This study evaluated the efficacy of valnoctamide (racemic-VCD), sec-butylpropylacetamide (racemic-SPD), and phenobarbital for stopping nerve agent seizures in both immature and adult rats.

Methods: Female and male postnatal day (PND) 21, 28, and 70 (adult) rats, previously implanted with electroencephalography (EEG) electrodes were exposed to seizure-inducing doses of the nerve agents sarin or VX and EEG was recorded continuously. Read More

Int J Geriatr Psychiatry 2019 09 8;34(9):1345-1350. Epub 2019 Feb 8.

Department of Pharmacy, Abdul Wali Khan University, Mardan, Pakistan.

Objective: Pyrus pashia has traditionally been used as a therapeutic agent including sedative. In this regard, hydroethanolic extract of Pyrus pashia (HEPP) was screened for phytochemical investigation, acute toxicity, and sedative-hypnotic activity to provide a scientific rationale to its ethno-medicinal uses.

Methods: Mice were used in acute toxicity test; sedative potential was observed in open field test while thiopental-induced sleeping time and barbiturate-induced sleeping time tests were used for the assessment of hypnotic like effects of HEPP. Read More

Environ Mol Mutagen 2019 01 19;60(1):42-46. Epub 2018 Oct 19.

Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan.

The Pig-a assay is an emerging and promising in vivo method to determine mutagenic potential of chemicals. Since its development in 2008, remarkable progress has been made in harmonizing and characterizing the test procedures, primarily using known mutagenic chemicals. The purpose of the present study was to evaluate specificity of the Pig-a assay using two nongenotoxic and well-characterized rodent liver carcinogens, phenobarbital and clofibrate, in male F344/DuCrl rats. Read More

J Mol Graph Model 2019 01 27;86:1-18. Epub 2018 Sep 27.

Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab, 160062, India; Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab, 160062, India. Electronic address:

Merbarone is a derivative of thiobarbituric acid, possessing catalytic inhibitory potential against human topoisomerase IIα (hTopoIIα). Merbarone was reported to inhibit DNA cleavage by hTopoIIα. It is important to understand the molecular mechanism of hTopoIIα inhibition by merbarone, as these details guide the rational design of new ligands. Read More

Epilepsy Behav 2018 11 5;88:212-217. Epub 2018 Oct 5.

Division of Neurology, Department of Pediatrics, UCLA Mattel Children's Hospital, USA; Department of Neurology, David Geffen School of Medicine at UCLA, USA.

Purpose: Seizures are common in term infants with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia. Although phenobarbital (PHB) is generally considered first-line therapy, some centers have embraced third-generation antiepileptic drugs (AEDs) such as levetiracetam (LEV) given the impression of comparable efficacy and superior tolerability. We set out to compare the efficacy of PHB and LEV in a large single-center cohort. Read More

Toxicol Sci 2019 01;167(1):172-189

National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.

Exposure to environmentally relevant chemicals that activate the xenobiotic receptors aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), and peroxisome proliferator-activated receptor alpha (PPARα) in rodent test systems often leads to increases in oxidative stress (OS) that contributes to liver cancer induction. We hypothesized that activation of the oxidant-induced transcription factor Nrf2 could be used as a surrogate endpoint for increases in OS. We examined the relationships between activation of xenobiotic receptors and Nrf2 using previously characterized gene expression biomarkers that accurately predict modulation. Read More

Rocz Panstw Zakl Hig 2018 ;69(3):307-314

Department of Toxicology and Health Risk Assessment, National Institute of Public Health – National Institute of Hygiene, Warsaw, Poland

Background: The changes in DNA methylation are considered as one of the early events in hepatocarcinogenesis.

Objective: We evaluated the ability of phenobarbital (PB) – the most widely used anticonvulsant worldwide and classical rodent liver carcinogen – to cause the promoter region of the c-myc protooncogene hypomethylation as well as changes of mRNA level of this gene. Moreover, the expression of Dnmt1 protein in rat treated with this compound was analyzed. Read More

Neurotox Res 2019 Jan 24;35(1):173-182. Epub 2018 Aug 24.

Department of Pharmacology and Physiology, Georgetown University, Washington, DC, 20007, USA.

The developing brain is uniquely susceptible to drug-induced increases in programmed cell death or apoptosis. Many compounds, including anticonvulsant drugs, anesthetic agents, and ethanol, when administered in a narrow postnatal window in rodents, result in increased pruning of neurons. Here, we report that dimethyl sulfoxide (DMSO) triggers widespread neurodegeneration in the immature (postnatal day, P7) rat brain, an effect consistent with a prior report in neonatal mice. Read More

Plant Physiol 2018 10 20;178(2):552-564. Epub 2018 Aug 20.

Division of Agricultural Sciences, Graduate School of Sciences and Technology for Innovation, Yamaguchi University, Yamaguchi 753-8515, Japan

Green leaf volatiles (GLVs), including six-carbon (C6) aldehydes, alcohols, and esters, are formed when plant tissues are damaged. GLVs play roles in direct plant defense at wound sites, indirect plant defense via the attraction of herbivore predators, and plant-plant communication. GLV components provoke distinctive responses in their target recipients; therefore, the control of GLV composition is important for plants to appropriately manage stress responses. Read More

Ther Drug Monit 2018 12;40(6):725-729

Department of Clinical Research, National Epilepsy Center, NHO, Shizuoka Institute of Epilepsy and Neurological Disorders.

Background: It is well-known that the pharmacokinetics of various drugs are influenced by inflammation. This study evaluated the relationship between C-reactive protein (CRP; an inflammation marker) and the pharmacokinetics of perampanel.

Methods: Among 111 patients who underwent measurement of both CRP and perampanel, 23 patients had a serum CRP level exceeding 1. Read More

Hum Mol Genet 2018 11;27(21):3688-3696

Hepatology Program, CIMA-University of Navarra, Spain.

A first-in-human gene therapy trial using a recombinant adeno-associated viral (rAAV) vector for acute intermittent porphyria (AIP) reveals that higher doses would be required to reach therapeutic levels of the porphobilinogen deaminase (PBGD) transgene. We developed a hyperfunctional PBGD protein to improve the therapeutic index without increasing vector dose. A consensus protein sequence from 12 mammal species was compared to the human PBGD sequence, and eight amino acids were selected. Read More

J Appl Toxicol 2018 12 25;38(12):1529-1537. Epub 2018 Jul 25.

Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 1-98, 3-Chome, Kasugade-Naka, Konohana-ku, Osaka, 554-8558, Japan.

Transcriptomics technologies have been used for risk assessment of chemicals, mainly to predict the modes of action (MOAs) of chemicals or identify biomarkers. Transcriptomics data may also be helpful to understand MOAs of chemicals at the molecular level in more detail. As an example of the known MOAs, there are two MOAs of thyroid toxicity: inhibition of thyroid hormone synthesis ("direct" effect) and hypermetabolism of thyroid hormone by enzyme induction in liver ("indirect" effect). Read More

J Pediatr Hematol Oncol 2019 03;41(2):e94-e96

Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota Medical Center, Minneapolis, MN.

Current treatment of high-grade osteosarcoma consists of preoperative chemotherapy, typically using some combination of doxorubicin, cisplatin, ifosfamide, and/or high-dose methotrexate followed by surgical resection. In this report, we present a case of a 21-year-old woman with high-grade osteosarcoma of the chest wall who received 5 times the planned dose of doxorubin and 4 times the planned dose of ifosfamide. She survived this chemotherapy overdose after administration of dimethyl sulfoxide and phenobarbital. Read More

Environ Sci Pollut Res Int 2018 Sep 27;25(25):25383-25389. Epub 2018 Jun 27.

Programa de Pós-Graduação em Ciências Ambientais, Laboratórios Integrados de Pesquisas em Ciências Químicas, Instituto de Ciências Naturais, Humanas e Sociais, Universidade Federal de Mato Grosso, Câmpus de Sinop, Av. Alexandre Ferronato, 1200, Setor Industrial, Sinop, MT, 78557-267, Brazil.

The toxicity of Roundup Original® (GLY), a glyphosate-based herbicide widely used in crops in Mato Grosso state, was determined in hybrid fish jundiara or pintado da Amazônia. The 96 h-LC of GLY was 13.57 mg L. Read More

J Hazard Mater 2018 09 17;358:494-502. Epub 2018 May 17.

Masaryk University, Faculty of Science, RECETOX, Kamenice 753/5, 625 00 Brno, Czech Republic. Electronic address:

Growth inhibition of freshwater microalga Pseudokirchneriella subcapitata caused by a waste water treatment plant (WWTP) effluent extract was investigated using an effect directed analysis (EDA) approach. The objective was to identify compounds responsible for the toxicity by combining state-of-the-art sampling, bioanalytical, fractionation and non-target screening techniques. Three fractionation steps of the whole extract were performed and bioactive fractions were analysed with GC (xGC)-MS and LC-HRMS. Read More

Ecotoxicol Environ Saf 2018 Sep 21;160:94-103. Epub 2018 May 21.

Center for Marine Environmental Studies, Ehime University, Bunkyo-cho 2-5, Matsuyama, Ehime prefecture, 790-8577 Japan. Electronic address:

This work aimed at evaluating the toxic effects of in ovo exposure to phenobarbital (PB) and unveiling the mode of action by transcriptome analysis in the embryonic liver of a model avian species, chicken (Gallus gallus). Embryos were initially treated with saline or 1 μg PB /g egg at Hamburger Hamilton Stage (HHS) 1 (1st day), followed by 20 days of incubation to HHS 46. At 21st day, chicks that pipped successfully were euthanized and dissected for assessing the PB caused effects on phenotypes and the liver transcriptome in both genders. Read More

Food Chem Toxicol 2018 Mar 7;113:322-327. Epub 2018 Feb 7.

Environmental Toxicology Laboratory, Department of Zoology, University of Rajasthan, Jaipur 302004, India. Electronic address:

Tartrazine is a synthetic lemon yellow azo dye primarily used as a food coloring. The present study aimed to screen the neurobiochemical effects of Tartrazine in Wistar rats after administering the Acceptable Daily Intake (ADI) level. Tartrazine (7. Read More

Neurotox Res 2018 08 7;34(2):173-187. Epub 2018 Feb 7.

Department of Neonatology, Charité-Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.

In preterm infants, phenobarbital is the first-line antiepileptic drug for neonatal seizures while caffeine is used for the treatment of apnea. Data from experimental animals suggest that phenobarbital and other anticonvulsants are toxic for the developing brain, while neuroprotective effects have been reported for caffeine both in newborn rodents and preterm human infants. To characterize the interaction of phenobarbital and caffeine in the hippocampus of the developing rodent brain, we examined the effects of both drugs given separately or together on postnatal neurogenesis after administration to neonatal rats throughout postnatal day (P) 4 to P6. Read More

Biol Pharm Bull 2018 ;41(2):247-253

Department of Pharmacognosy, School of Pharmacy, Kitasato University.

Ephedrine alkaloids-free Ephedra Herb extract (EFE) has been developed to eliminate the adverse effects caused by ephedrine alkaloid-induced sympathetic hyperactivation. Previously, we reported that EFE possesses analgesic, anti-influenza, and cancer metastatic inhibitory effects at comparable levels to that of Ephedra Herb extract (EHE). However, it has not yet been demonstrated that EFE is free from the known side effects of EHE, such as excitation, insomnia, and arrhythmias. Read More

Biochemistry 2018 02 30;57(7):1262-1273. Epub 2018 Jan 30.

Department of Biochemistry and Molecular Biology, ‡Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences , Little Rock, Arkansas 72205-7199, United States.

Translesion DNA synthesis (TLS) performed by human DNA polymerase eta (hpol η) allows tolerance of damage from cis-diamminedichloroplatinum(II) (CDDP or cisplatin). We have developed hpol η inhibitors derived from N-aryl-substituted indole barbituric acid (IBA), indole thiobarbituric acid (ITBA), and indole quinuclidine scaffolds and identified 5-((5-chloro-1-(naphthalen-2-ylmethyl)-1H-indol-3-yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (PNR-7-02), an ITBA derivative that inhibited hpol η activity with an IC value of 8 μM and exhibited 5-10-fold specificity for hpol η over replicative pols. We conclude from kinetic analyses, chemical footprinting assays, and molecular docking that PNR-7-02 binds to a site on the little finger domain and interferes with the proper orientation of template DNA to inhibit hpol η. Read More

Arch Toxicol 2018 Feb 21;92(2):953-966. Epub 2017 Dec 21.

Department of Medicine I, Comprehensive Cancer Center, Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, 1090, Vienna, Austria.

Many frequently prescribed drugs are non-genotoxic carcinogens (NGC) in rodent liver. Their mode of action and health risks for humans remain to be elucidated. Here, we investigated the impact of two model NGC, the anti-epileptic drug phenobarbital (PB) and the contraceptive cyproterone acetate (CPA), on intrahepatic epithelial-mesenchymal crosstalk and on growth of first stages of hepatocarcinogenesis. Read More

J Evid Based Complementary Altern Med 2017 10 7;22(4):753-759. Epub 2017 Nov 7.

4 School of Pharmacy, University of Ghana, Legon, Accra, Ghana.

Extracts of Desmodium adscendens (Sw) DC are used for the treatment of various diseases but limited toxicological evaluations have been done on the medicinal plant. This study investigates toxicity effects of the leave extract of D adscendens, and the possibility of drug-drug interaction of the plant extract when co-administered with other drugs. Oral administrations of leaf extract of D adscendens to white Wistar rats in an acute toxicity studies allowed the estimation of an LD (median lethal dose) value of 1122 mg/kg body weight. Read More

Georgian Med News 2017 Nov(272):138-144

Azerbaijan Medical University, Baku, Azerbaijan.

Acute poisoning of chemical etiology is a significant global public health problem. The aim of this study was the analysis of the toxicoepidemiological structure of psychopharmacological drugs poisoning in Azerbaijan. We collected and analyzed the data on all cases of acute poisoning by psychopharmacological drugs (codes of categories T42/T43 ICD-10) undergoing inpatient treatment at the Center of Clinical Toxicology in Baku, Azerbaijan in 2009-2016. Read More

Eur J Med Chem 2018 Jan 27;143:829-842. Epub 2017 Nov 27.

CICS-UBI - Health Sciences Research Centre, University of Beira Interior, 6200-506 Covilhã, Portugal; Department of Chemistry, University of Beira Interior, 6201-001 Covilhã, Portugal.

Barbituric and thiobarbituric acid derivatives have become progressively attractive to medicinal chemists due to their wide range of biological activities. Herein, different series of 1,3,5-trisubstituted barbiturates and thiobarbiturates were prepared in moderate to excellent yields and their activity as xanthine oxidase inhibitors, antioxidants, antibacterial agents and as anti-proliferative compounds was evaluated in vitro. Interesting bioactive barbiturates were found namely, 1,3-dimethyl-5-[1-(2-phenylhydrazinyl)ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6c) and 1,3-dimethyl-5-[1-[2-(4-nitrophenyl)hydrazinyl]ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6e), which showed concomitant xanthine oxidase inhibitory effect (IC values of 24. Read More

Neonatology 2018 24;113(2):117-121. Epub 2017 Nov 24.

Department of Nephrology, Monash Children's Hospital, Clayton, VIC, Australia.

Background: Phenobarbitone (PB) is the first-line anti-convulsant for neonatal seizures. The use of peritoneal dialysis (PD) to enhance drug elimination in cases of neonatal PB overdose has not been reported.

Objective: To report a case of neonatal severe PB toxicity and review the elimination of PB by PD. Read More

Pharmacogn Mag 2017 Oct 11;13(Suppl 3):S567-S572. Epub 2017 Oct 11.

Department of Biochemistry, S.D.M. Centre for Research in Ayurveda and Allied Sciences, Kuthpady, Udupi, Karnataka, India.

Background: Aluminum chloride (AlCl) is a known potent environmental neurotoxin causing progressive neurodegenerative changes in the brain. The herb is commonly known as "Rasana" and used as a nerve tonic in neuroinflammatory conditions in Indian system of medicine.

Objective: To evaluate the neuroprotective activity of hydroalcoholic extract of in chronic AlCl-induced neurotoxicity in Swiss albino mice. Read More

J Toxicol Sci 2017 ;42(6):773-788

Environmental Health Science Laboratory, Sumitomo Chemical Company, Ltd.

High dietary levels of the non-genotoxic synthetic pyrethroid momfluorothrin increased the incidence of hepatocellular tumors in male and female Wistar rats. Mechanistic studies have demonstrated that the mode of action (MOA) for momfluorothrin-induced hepatocellular tumors is constitutive androstane receptor (CAR)-mediated. In the present study, to evaluate the potential human carcinogenic risk of momfluorothrin, the effects of momfluorothrin (1-1,000 µM) and a major metabolite Z-CMCA (5-1,000 µM) on hepatocyte replicative DNA synthesis and CYP2B mRNA expression were examined in cultured rat and human hepatocyte preparations. Read More

Drug Metab Lett 2017;11(2):144-148

PK Sciences, Global Biotransformation, Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, MA 02139, United States.

Background: 4-(piperazin-1-yl)-8-(trifluoromethyl)pyrido[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (1) is a small-molecule which demonstrated a sub-nM inhibitory potency toward the histamine H4 receptor (H4R). However, it was found to be mutagenic in an in vitro Ames assay. Metabolic bioactivation of 1 could potentially arise from the piperazine moiety by forming reactive intermediates such as glyoxal, aldehyde-imine and/or iminium ion, which could all lead to genotoxicity. Read More

Anesth Analg 2018 04;126(4):1377-1380

From the Department of Anesthesiology, University Hospital Duesseldorf, Duesseldorf, Germany.

Remote ischemic preconditioning (RIPC) seems to be a promising cardioprotective strategy with contradictive clinical data suggesting the anesthetic regimen influencing the favorable impact of RIPC. This study aimed to investigate whether cardio protection by RIPC is abolished by anesthetic regimens. Male Wistar rats were randomized to 6 groups. Read More

Mol Med Rep 2017 Aug 8;16(2):1559-1564. Epub 2017 Jun 8.

Department of Anesthesiology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan 450007, P.R. China.

Diosgenin is a steroidal saponin extract from numerous plants, including Solanum and Dioscorea species, and has been reported to possess neuroprotective activity. However, the role of diosgenin in neuropathic pain remains unclear. The present study examined the effects of diosgenin on allodynia and the levels of inflammatory mediators in rats following neuropathic pain evoked by chronic constriction injury (CCI). Read More

Int J Mol Sci 2017 Sep 21;18(10). Epub 2017 Sep 21.

Departamento de Investigación Agroambiental, IMIDRA, Finca "El Encín", Autovía del Noreste A-2 Km 38.2, 28800 Alcalá de Henares, Madrid, Spain.

Plant growth promoting endophytic bacteria (PGPB) isolated from were inoculated in two cultivars of (VR and D19) growing on sand supplemented with 0.1 mM Cd or 1 mM Zn. Plant growth, concentrations of metals and thiobarbituric acid (TBA) reactive compounds were determined. Read More

J Pharmacol Exp Ther 2017 12 19;363(3):336-347. Epub 2017 Sep 19.

GlaxoSmithKline, King of Prussia, Pennsylvania (JLA, DFA, DF, TS, KJD, MP, MB, KW) and while at GlaxoSmithKline, King of Prussia, Pennsylvania (LL, EHDF, CE-M).

Decreased erythropoietin (EPO) production, shortened erythrocyte survival, and other factors reducing the response to EPO contribute to anemia in patients who have a variety of underlying pathologies such as chronic kidney disease. Treatment with recombinant human EPO (rHuEPO) at supraphysiologic concentrations has proven to be efficacious. However, it does not ameliorate the condition in all patients, and it presents its own risks, including cardiovascular complications. Read More

Anesthesiology 2017 11;127(5):838-851

From the Department of Physiology and Pharmacology (M.-C.K.) and the Department of Physiology and Pharmacology and Program in Neuroscience (L.S.L.), The University of Western Ontario, London, Ontario, Canada.

Background: Previous studies showed that synaptic transmission is affected by general anesthetics, but an anesthetic dose response in freely moving animals has not been done. The hippocampus provides a neural network for the evaluation of isoflurane and pentobarbital on multisynaptic transmission that is relevant to memory function.

Methods: Male Long-Evans rats were implanted with multichannel and single electrodes in the hippocampus. Read More