6,438 results match your criteria Toxicity Sedative-Hypnotics


Effect of the metabolic capacity in rat liver S9 on the positive results of in vitro micronucleus tests.

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

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http://dx.doi.org/10.2131/jts.44.145DOI Listing
March 2019
1 Read

Gas Anesthesia Impairs Peripheral Auditory Sensitivity in Barn Owls ().

eNeuro 2018 Sep-Oct;5(5). Epub 2018 Nov 12.

Department of Neuroscience, School of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, 26129 Oldenburg, Germany.

Auditory nerve single-unit recordings were obtained from two groups of young barn owls (age, between posthatching days 11 and 86) in terminal experiments under two different anesthetic regimes: ketamine (6-11 mg/kg) plus xylazine (∼2 mg/kg); or isoflurane (1-1.5%) in oxygen, delivered via artificial respiration. In a second series of minimally invasive experiments, auditory brainstem responses (ABRs) were recorded in the same four adult barn owls (; age, between 5 and 32 months) under three different anesthetic protocols: ketamine (10 mg/kg) plus xylazine (3 mg/kg), isoflurane (1-1. Read More

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http://dx.doi.org/10.1523/ENEURO.0140-18.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354786PMC
April 2019
1 Read

Dexmedetomidine enhances ropivacaine-induced sciatic nerve injury in diabetic rats.

Br J Anaesth 2019 Jan 4;122(1):141-149. Epub 2018 Oct 4.

Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK. Electronic address:

Background: Previous studies suggest that dexmedetomidine has a protective effect against local anaesthetic-induced nerve injury in regional nerve blocks. Whether this potentially protective effect exists in the context of diabetes mellitus is unknown.

Methods: A diabetic state was established in adult male Sprague-Dawley rats with intraperitoneal injection of streptozotocin. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00070912183069
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http://dx.doi.org/10.1016/j.bja.2018.08.022DOI Listing
January 2019
2 Reads

Investigating tissue bioconcentration and the behavioural effects of two pharmaceutical pollutants on sea trout (Salmo trutta) in the laboratory and field.

Aquat Toxicol 2019 Feb 1;207:170-178. Epub 2018 Dec 1.

Department of Ecology and Environmental Science, Umeå University, SE-90187, Umeå, Sweden; Department of Wildlife, Fish and Environmental Studies, Swedish University of Agricultural Sciences, SE-90183, Umeå, Sweden.

Pharmaceuticals entering aquatic ecosystems via wastewater effluents are of increasing concern for wild animals. Because some pharmaceuticals are designed to modulate human behaviour, measuring the impacts of exposure to pharmaceuticals on fish behaviour has become a valuable endpoint. While laboratory studies have shown that pharmaceuticals can affect fish behaviour, there is a lack of understanding if behaviour is similarly affected in natural environments. Read More

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http://dx.doi.org/10.1016/j.aquatox.2018.11.028DOI Listing
February 2019
2 Reads

The anti-apoptotic effect of nerve growth factor on propofol-induced neurotoxicity in hippocampal neurons is Rac1 dependent.

Pharmazie 2018 12;73(12):706-710

Propofol has been considered as a near-ideal anesthetic agent since its introduction 40 years ago. However, the side effects of propofol including bacterial contamination, hyperlipidemia, and neurotoxicity also aroused attention. Nerve growth factor (NGF) plays a pivotal role in the development, differentiation, and survival of the neurons of the peripheral and central nervous system. Read More

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http://dx.doi.org/10.1691/ph.2018.8726DOI Listing
December 2018
3 Reads

Determination of emerging chlorinated byproducts of diazepam in drinking water.

Chemosphere 2019 Mar 15;218:223-231. Epub 2018 Nov 15.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China; Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control, Beijing, 100013, China. Electronic address:

Diazepam (DZP) is often found in source water and drinking water at dozens of nanograms per liter levels. The transformation of DZP in water chlorination disinfection process has aroused new concern because the toxic disinfection byproducts (DBPs) might be produced. However, the DBPs of DZP have not been fully identified, and their occurrence levels in drinking water have not been reported. Read More

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http://dx.doi.org/10.1016/j.chemosphere.2018.11.076DOI Listing
March 2019
2 Reads

LC-MS/MS analysis of the plasma concentrations of a cocktail of 5 cytochrome P450 and P-glycoprotein probe substrates and their metabolites using subtherapeutic doses.

J Pharm Biomed Anal 2019 Feb 28;164:430-441. Epub 2018 Oct 28.

School of Pharmaceutical Sciences of Ribeirão Preto, Department of Clinical Analysis, Toxicology and Food Science, University of São Paulo, Brazil; Ribeirão Preto Medical School, Department of Internal Medicine, University of São Paulo, Brazil. Electronic address:

Drug transporters and CYP enzymes are important sources of pharmacokinetics (PK) variability in drug responses and can cause various pharmacological and toxicological consequences, leading to either toxicity or an insufficient pharmacological effect. In recent years, the cocktail approach was developed to determine in vivo CYP and transporters activities, but these approaches are somewhat limited. We described the development and validation of three sensitive and specific LC-MS/MS assays for the determination of P-gp and major human CYP isoenzyme activities following oral administration of a drug cocktail of subtherapeutic doses (lower than 10 times) of caffeine (CAF), omeprazole (OME), losartan (LOS), midazolam (MDZ), metoprolol (METO) and fexofenadine (FEX) in healthy volunteers. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S07317085183106
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http://dx.doi.org/10.1016/j.jpba.2018.10.029DOI Listing
February 2019
7 Reads

Soman-induced status epilepticus, epileptogenesis, and neuropathology in carboxylesterase knockout mice treated with midazolam.

Epilepsia 2018 12 25;59(12):2206-2218. Epub 2018 Oct 25.

US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland.

Objective: Exposure to chemical warfare nerve agents (CWNAs), such as soman (GD), can induce status epilepticus (SE) that becomes refractory to benzodiazepines when treatment is delayed, leading to increased risk of epileptogenesis, severe neuropathology, and long-term behavioral and cognitive deficits. Rodent models, widely used to evaluate novel medical countermeasures (MCMs) against CWNA exposure, normally express plasma carboxylesterase, an enzyme involved in the metabolism of certain organophosphorus compounds. To better predict the efficacy of novel MCMs against CWNA exposure in human casualties, it is crucial to use appropriate animal models that mirror the human condition. Read More

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http://doi.wiley.com/10.1111/epi.14582
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http://dx.doi.org/10.1111/epi.14582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334636PMC
December 2018
17 Reads

Comparison of inhaled versus intravenous anesthesia for laryngoscopy and laryngeal electromyography in a rat model.

J Otolaryngol Head Neck Surg 2018 Oct 20;47(1):64. Epub 2018 Oct 20.

Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Alberta, 2C3.57 Walter MacKenzie Centre, Edmonton, AB, T6G 2R7, Canada.

Background: Propofol and remifentanil intravenous combination is one popular form of total intravenous anesthesia (TIVA) in mainstream clinical practice, but it has rarely been applied to a rat model for laryngoscopy and laryngeal electromyography (LEMG). Our objective was to establish a safe and reproducible general anesthetic protocol for laryngoscopy and endoscopic LEMG in a rat model. Our hypothesis is that TIVA allows a minimally morbid, and feasible laryngoscopy and LEMG. Read More

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https://journalotohns.biomedcentral.com/articles/10.1186/s40
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http://dx.doi.org/10.1186/s40463-018-0312-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196000PMC
October 2018
5 Reads

Pilot studies evaluating the nongenotoxic rodent carcinogens phenobarbital and clofibrate in the rat Pig-a assay.

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

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http://dx.doi.org/10.1002/em.22232DOI Listing
January 2019
2 Reads

Ectopic expression of OX1R in ulcerative colitis mediates anti-inflammatory effect of orexin-A.

Biochim Biophys Acta Mol Basis Dis 2018 11 18;1864(11):3618-3628. Epub 2018 Aug 18.

INSERM UMR1149/Inflammation Research Center (CRI), Team "From inflammation to cancer in digestive diseases" labeled by "la Ligue Nationale contre le Cancer", Paris-Diderot University, DHU UNITY, 75018 Paris, France. Electronic address:

Orexins (orexin-A and orexin-B) are hypothalamic peptides that are produced by the same precursor and are involved in sleep/wake control, which is mediated by two G protein-coupled receptor subtypes, OX1R and OX2R. Ulcerative colitis (UC) is an inflammatory bowel disease, (IBD) which is characterized by long-lasting inflammation and ulcers that affect the colon and rectum mucosa and is known to be a significant risk factor for colon cancer development. Based on our recent studies showing that OX1R is aberrantly expressed in colon cancer, we wondered whether orexin-A could play a role in UC. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S09254439183031
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http://dx.doi.org/10.1016/j.bbadis.2018.08.023DOI Listing
November 2018
23 Reads

Presentations to the emergency department with non-medical use of benzodiazepines and Z-drugs: profiling and relation to sales data.

Eur J Clin Pharmacol 2019 Jan 22;75(1):77-85. Epub 2018 Sep 22.

Clinical Toxicology, Guy's and St Thomas' Hospitals NHS Foundation Trust, and King's Health Partners, London, UK.

Background: Non-medical use of benzodiazepines and Z-drugs is common; however, there is limited information available on the extent of harm related to this in Europe, as well as the relationship between misuse and availability.

Aim: To describe presentations to the emergency department in Europe related to the recreational use of benzodiazepines and Z-drugs and compare regional differences in these presentations with legal drug sales of benzodiazepines and Z-drugs within each country.

Methods: Emergency department presentations with recreational misuse of benzodiazepines and Z-drugs were obtained from the Euro-DEN dataset for the period from October 2013 to September 2015; data extracted included demographics, clinical features, reported coused drugs, and outcome data. Read More

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http://link.springer.com/10.1007/s00228-018-2550-1
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http://dx.doi.org/10.1007/s00228-018-2550-1DOI Listing
January 2019
28 Reads

Effects of repeated anaesthesia on gill and general health of Atlantic salmon, Salmo salar.

J Fish Biol 2018 Dec 28;93(6):1069-1081. Epub 2018 Nov 28.

Marine Laboratory, Marine Scotland Science, Aberdeen, UK.

Fish are the second most widely utilized vertebrate group used for scientific procedures in the United Kingdom, but the development and application of 3Rs (the principles of replacement, reduction, and refinement) in aquaculture disease research lags behind methodologies in place for mammalian studies. With a need for individual monitoring and non-lethal sampling, the effect of repeat anaesthesia on experimental fish needs to be better understood. This study analyses the effect of repeat anaesthesia with MS-222, metomidate and AQUI-S upon the gill and general health of post-smolt Atlantic salmon Salmo salar. Read More

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http://dx.doi.org/10.1111/jfb.13803DOI Listing
December 2018
5 Reads
1.658 Impact Factor

Dexmedetomidine ameliorates lidocaine-induced spinal neurotoxicity via inhibiting glutamate release and the PKC pathway.

Neurotoxicology 2018 12 18;69:77-83. Epub 2018 Sep 18.

Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623, China. Electronic address:

Dexmedetomidine, a selective α adrenergic agonist, has been shown to have neuroprotective and anti-apoptotic effects. To further investigate the underlying mechanisms, we used a rat model of spinal neurotoxicity induced by intrathecal administration of lidocaine. Four days after intrathecal catheter implantation, rats received an intraperitoneal injection of various doses of dexmedetomidine before an intrathecal injection of 20 μL 10% lidocaine. Read More

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http://dx.doi.org/10.1016/j.neuro.2018.09.004DOI Listing
December 2018
1 Read

Sedative-hypnotic like effect of 5-methoxyflavone in mice and investigation on possible mechanisms by in vivo and in silico methods.

Biomed Pharmacother 2018 Dec 12;108:85-94. Epub 2018 Sep 12.

Department of Pharmaceutical Chemistry, VISTAS, VELS school of Pharmaceutical Sciences, Chennai, 600117, Tamilnadu, India. Electronic address:

Flavonoids have been shown to possess central nervous system (CNS) depressant effect mediated through the ionotropic GABA receptors. In the present study, 5-methoxyflavone was evaluated for sedative-hypnotic like activity in mice and the mechanisms involved by employing a battery of tests including molecular docking studies. In the open field test, 5-methoxyflavone in various doses (50, 100 and 150 mg/kg, i. Read More

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http://dx.doi.org/10.1016/j.biopha.2018.08.117DOI Listing
December 2018
3 Reads
2.023 Impact Factor

A patient full of surprises: a body packer with cocaine intoxication, pneumococcal pneumonia and HIV infection.

BMC Emerg Med 2018 09 4;18(1):29. Epub 2018 Sep 4.

Emergency Department, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.

Background: Smuggling of illegal drugs by hiding them inside one's own body, also called body packing, is a worldwide phenomenon. Cocaine is the most frequently transported drug. Body packing is a potentially lethal practice. Read More

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http://dx.doi.org/10.1186/s12873-018-0180-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6123965PMC
September 2018
9 Reads

Relationship between In Vivo CYP3A4 Activity, CYP3A5 Genotype, and Systemic Tacrolimus Metabolite/Parent Drug Ratio in Renal Transplant Recipients and Healthy Volunteers.

Drug Metab Dispos 2018 11 30;46(11):1507-1513. Epub 2018 Aug 30.

Departments of Microbiology and Immunology (T.V., H.d.J., H.d.L., D.R.J.K.), Pharmaceutical and Pharmacological Sciences (J.d.H.), and Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences (M.O., P.A.), Catholic University of Leuven, Leuven, Belgium; Department of Nephrology and Renal Transplantation (T.V., H.d.J., H.d.L., D.R.J.K.), and Center for Clinical Pharmacology (J.d.H.), University Hospitals Leuven, Leuven, Belgium; Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Stockholm, Sweden; (A.P.); and Department of Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden (A.P.)

CYP3A5 genotype is a major determinant of tacrolimus clearance, and has been shown to affect systemic tacrolimus metabolite/parent ratios in healthy volunteers, which may have implications for efficacy and toxicity. In a cohort of 50 renal transplant recipients who underwent quantification of CYP3A4 activity using the oral midazolam drug probe, we confirmed that CYP3A5 genotype is the single most important determinant of tacrolimus metabolite/parent ratio [CYP3A5 expressors displayed 2.7- and 2-fold higher relative exposure to 13-desmethyltacrolimus (DMT) and 31-DMT, respectively; < 0. Read More

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http://dx.doi.org/10.1124/dmd.118.081935DOI Listing
November 2018
8 Reads

Midazolam is effective to reduce cortical network activity in organotypic cultures during severe cholinergic overstimulation with soman.

Toxicol Lett 2018 Nov 27;297:19-23. Epub 2018 Aug 27.

Experimental Anesthesiology Section, Department of Anesthesiology and Intensive Care Medicine, Eberhard-Karls-University, Waldhoernlestrasse 22, 72072 Tuebingen, Germany. Electronic address:

Intoxication with organophosphorus compounds can result in life-threatening organ dysfunction and refractory seizures. Sedation or hypnosis is essential to facilitate mechanical ventilation and control seizure activity. The range of indications for midazolam includes both hypnosis and seizure control. Read More

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http://dx.doi.org/10.1016/j.toxlet.2018.08.016DOI Listing
November 2018
31 Reads
3.262 Impact Factor

Effect of aflatoxin B, benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells.

Food Chem Toxicol 2018 Nov 26;121:214-223. Epub 2018 Aug 26.

Division of Biochemical Toxicology, National Center for Toxicological Research, 3900 NCTR Rd, Jefferson, AR, 72079, USA. Electronic address:

The increasing number of man-made chemicals in the environment that may pose a carcinogenic risk highlights the need for developing reliable time- and cost-effective approaches for carcinogen detection and identification. To address this issue, we investigated the utility of high-throughput microarray gene expression and next-generation genome-wide DNA methylation sequencing for the in vitro identification of genotoxic and non-genotoxic carcinogens. Terminally differentiated and metabolically competent human liver HepaRG cells were treated at minimally cytotoxic concentrations of (i) the genotoxic human liver carcinogen aflatoxin B (AFB1) and its structural non-carcinogenic analog aflatoxin B (AFB2); (ii) the genotoxic human lung carcinogen benzo[a]pyrene (B[a]P) and its non-carcinogenic isomer benzo[e]pyrene (B[e]P); and (iii) the non-genotoxic liver carcinogen methapyrilene for 72 h and transcriptomic and DNA methylation profiles were examined. Read More

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http://dx.doi.org/10.1016/j.fct.2018.08.034DOI Listing
November 2018
12 Reads

Catatonia After Liver Transplantation.

Ann Transplant 2018 Aug 28;23:608-614. Epub 2018 Aug 28.

Department of Surgery, Division of Abdominal Transplant, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.

BACKGROUND Central nervous system complications after transplantation occur in up to 40% of recipients and these complications are associated with increased length of hospital stay and mortality. Catatonia is a neuropsychiatric clinical syndrome which has been described in case reports and in a small case series as occurring in the immediate post-solid organ transplantation (SOT) period, and it has been attributed to calcineurin inhibitor neurotoxicity, psychological vulnerability, and depression. Among transplant recipients, the incidence of catatonia is unknown; it may be under diagnosed in part due to a broad differential diagnosis in the post-transplantation setting, which includes hypoactive delirium, non-convulsive status epilepticus, drug toxicity, conversion disorder, and volitional uncooperativeness. Read More

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https://www.annalsoftransplantation.com/abstract/index/idArt
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http://dx.doi.org/10.12659/AOT.910298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6248284PMC
August 2018
9 Reads

Hypomethylation of the c-myc promoter region induced by phenobarbital in rat liver

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

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November 2018
3 Reads

Neuroprotective Action of the CB1/2 Receptor Agonist, WIN 55,212-2, against DMSO but Not Phenobarbital-Induced Neurotoxicity in Immature Rats.

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

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http://dx.doi.org/10.1007/s12640-018-9944-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318010PMC
January 2019
6 Reads

Potentiation of antiseizure and neuroprotective efficacy of standard nerve agent treatment by addition of tariquidar.

Neurotoxicology 2018 09 18;68:167-176. Epub 2018 Aug 18.

CBRN Protection, TNO Defense, Safety and Security, Rijswijk, PO Box 2280 AA, The Netherlands. Electronic address:

Organophosphate (OP) induced seizures are commonly treated with anticholinergics, oximes and anticonvulsants. Inhibition of P-glycoprotein (PgP) has been shown to enhance the efficacy of nerve agent treatment in soman exposed rats. In the present study, the promising effects of the PgP inhibitor tariquidar were investigated in more detail in rats s. Read More

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http://dx.doi.org/10.1016/j.neuro.2018.08.005DOI Listing
September 2018
9 Reads

Identification of a Hexenal Reductase That Modulates the Composition of Green Leaf Volatiles.

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

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http://dx.doi.org/10.1104/pp.18.00632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181032PMC
October 2018
3 Reads

Dexmedetomidine Protects Against Chemical Hypoxia-Induced Neurotoxicity in Differentiated PC12 Cells Via Inhibition of NADPH Oxidase 2-Mediated Oxidative Stress.

Neurotox Res 2019 Jan 15;35(1):139-149. Epub 2018 Aug 15.

Department of Anesthesiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, No. 651, Dongfeng Road East, Guangzhou, 510060, Guangdong, China.

Dexmedetomidine (Dex) is a widely used sedative in anesthesia and critical care units, and it exhibits neuroprotective activity. However, the precise mechanism of Dex-exerted neuroprotection is not clear. Increased neuronal NADPH oxidase 2 (NOX2) contributes to oxidative stress and neuronal damage in various hypoxia-related neurodegenerative disorders. Read More

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http://dx.doi.org/10.1007/s12640-018-9938-7DOI Listing
January 2019
24 Reads

Optimal concentration of the transversus abdominis plane block in enhanced recovery after surgery protocols for patients of advanced age undergoing laparoscopic rectal cancer surgery.

J Int Med Res 2018 Nov 15;46(11):4437-4446. Epub 2018 Aug 15.

1 Anesthesiology Department, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.

Objective: The transversus abdominis plane (TAP) block ameliorates visual analogue scale scores and decreases morphine requirements, but its role remains unclear. Patients of advanced age are susceptible to local anesthetic intoxication. We aimed to identify an optimal concentration that can be used in enhanced recovery after surgery (ERAS) without compromising analgesic efficacy. Read More

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http://dx.doi.org/10.1177/0300060518790699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6259369PMC
November 2018
10 Reads

Dexmedetomidine attenuates lipopolysaccharide induced acute lung injury by targeting NLRP3 via miR-381.

J Biochem Mol Toxicol 2018 Nov 13;32(11):e22211. Epub 2018 Aug 13.

Department of Pain, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250012, Shandong, China.

Dexmedetomidine (Dex) is an agonist of α2-adrenergic receptors, and it is used as an anxiety reducing, sedative, and pain medication in clinical. Studies have shown that dexmedetomidine protects against lipopolysaccharide (LPS)-induced acute lung injury; however, the underlying mechanism is still unclear. To investigate, an acute lung injury mouse model was induced by intraperitoneal injection of LPS. Read More

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http://doi.wiley.com/10.1002/jbt.22211
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http://dx.doi.org/10.1002/jbt.22211DOI Listing
November 2018
10 Reads

Influence of Inflammation on the Pharmacokinetics of Perampanel.

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

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http://dx.doi.org/10.1097/FTD.0000000000000556DOI Listing
December 2018
20 Reads

Bioengineered PBGD variant improves the therapeutic index of gene therapy vectors for acute intermittent porphyria.

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

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http://dx.doi.org/10.1093/hmg/ddy283DOI Listing
November 2018
4 Reads

Serotonin Syndrome in the Perioperative Setting.

Am J Case Rep 2018 Jul 16;19:833-835. Epub 2018 Jul 16.

Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA.

BACKGROUND Serotonin syndrome is a life-threatening condition that can lead to neurologic complications and is associated with the use of serotonergic medications. As the use of antidepressant medications has increased, the incidence of perioperative serotonin syndrome has transitioned from a rare diagnosis to one that should be considered as a differential diagnosis for any patient displaying signs of neuroexcitation. CASE REPORT A 70-year-old man (ASA 2) with a history of vestibular migraines (treated with venlafaxine), gastroesophageal reflux disease, and benign prostatic hyperplasia presented to our institution for photoselective vaporization of the prostate. Read More

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http://dx.doi.org/10.12659/AJCR.909497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061453PMC
July 2018
20 Reads

In Vivo Study on Analgesic, Muscle-Relaxant, Sedative Activity of Extracts of and In Silico of Certain Compounds Present in This Species.

Biomed Res Int 2018 13;2018:3868070. Epub 2018 May 13.

Bioinformatics and Medical Informatics Research Center, San Diego State University, San Diego, CA 92182, USA.

Background: (flatweed) from the family Asteraceae is a medicinal plant found in Europe, Middle East, and India. In folkloric medication, it is used to heal jaundice, dyspepsia, constipation, rheumatism, and hypoglycemia as well as renal problems. Leaves and roots of the plant have antioxidant and antibacterial properties. Read More

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http://dx.doi.org/10.1155/2018/3868070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016213PMC
January 2019
8 Reads

Dexmedetomidine protects high-glucose induced apoptosis in human retinal pigment epithelial cells through inhibition on p75(NTR).

Biomed Pharmacother 2018 Oct 11;106:466-471. Epub 2018 Jul 11.

Department of Anesthesiology, Jining First People's Hospital, Jining, 272100, China. Electronic address:

Background: In both human patients and animals, diabetic condition of high blood glucose induced significant apoptotic responses in retinal pigment epithelial (RPE) cells. In this work, we used an in vitro culture model of human ARPE-19 cells to evaluate whether dexmedetomidine (DEX) may protect high d-glucose (DG)-induced diabetic apoptosis.

Methods: ARPE-19 cells were incubated with DG in vitro to induce apoptosis. Read More

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http://dx.doi.org/10.1016/j.biopha.2018.06.117DOI Listing
October 2018
6 Reads

Tricyclic antidepressants inhibit Candida albicans growth and biofilm formation.

Int J Antimicrob Agents 2018 Oct 7;52(4):500-505. Epub 2018 Jul 7.

Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy; Interdepartmental Centre SITEIA.PARMA, University of Parma, Parma, Italy.

Candida albicans is a commensal yeast of the human body, able to form biofilms on solid surfaces such as implanted medical devices, and contributes to nosocomial infections. Biofilms have the capacity to resist higher levels of antifungals compared with planktonic cells, and can develop tolerance to commonly used treatments. The necessity to overcome acquired drug resistance and identify new active molecules with low toxicity is a significant problem. Read More

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http://dx.doi.org/10.1016/j.ijantimicag.2018.06.023DOI Listing
October 2018
4 Reads

A Case Study Involving U-47700, Diclazepam and Flubromazepam-Application of Retrospective Analysis of HRMS Data.

J Anal Toxicol 2018 Nov;42(9):655-660

Forensic Science SA (Toxicology), Adelaide, South Australia, Australia.

The number of new psychoactive substances (NPS) available is constantly increasing, making it difficult for toxicology laboratories to keep screening methods up to date. Full scan high-resolution mass spectrometry (HRMS) is a versatile technique which allows for progressive updating of spectral databases to increase the scope of screening. It also allows for retrospective screening of data-specifically, reprocessing of data files using an updated spectral database without the need for re-extraction or reanalysis. Read More

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http://dx.doi.org/10.1093/jat/bky039DOI Listing
November 2018
12 Reads

[Machine Learning-based Prediction of Seizure-inducing Action as an Adverse Drug Effect].

Yakugaku Zasshi 2018 ;138(6):809-813

Graduate School of Pharmaceutical Sciences, The University of Tokyo.

 During the preclinical research period of drug development, animal testing is widely used to help screen out a drug's dangerous side effects. However, it remains difficult to predict side effects within the central nervous system. Here, we introduce a machine learning-based in vitro system designed to detect seizure-inducing side effects before clinical trial. Read More

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https://www.jstage.jst.go.jp/article/yakushi/138/6/138_17-00
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http://dx.doi.org/10.1248/yakushi.17-00213-1DOI Listing
August 2018
31 Reads

Neuroprotective effect of zolpidem against glutamate-induced toxicity is mediated via the PI3K/Akt pathway and inhibited by PK11195.

Toxicology 2018 08 30;406-407:58-69. Epub 2018 May 30.

Division of Molecular Medicine, Rudjer Boskovic Institute, Bijenička cesta 54, Zagreb, Croatia.

Excitotoxicity is a pathological process in which neuronal dysfunction and death are induced by excessive glutamate stimulation, the major fast excitatory neurotransmitter in the mammalian brain. Excitotoxicity-induced neurodegeneration is a contributing factor in ischemia-induced brain damage, traumatic brain injury, and various neurodegenerative diseases. It is triggered by calcium overload due to prolonged over-activation of ionotropic N-methyl-d-aspartate (NMDA) receptors. Read More

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http://dx.doi.org/10.1016/j.tox.2018.05.014DOI Listing
August 2018
4 Reads

Propofol Protects Rat Cardiomyocytes from Anthracycline-Induced Apoptosis by Regulating MicroRNA-181a and .

Oxid Med Cell Longev 2018 18;2018:2109216. Epub 2018 Apr 18.

Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.

We aimed to evaluate the cardioprotective effect and mechanism of propofol in anthracycline-induced cardiomyocyte apoptosis. We selected the rat myocardial cell line, H9c2, and primary cardiomyocytes for study. The cardiomyocytes were treated with vehicle, Adriamycin® (ADM), propofol, or a combination of ADM and propofol. Read More

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http://dx.doi.org/10.1155/2018/2109216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5932430PMC
October 2018
10 Reads

Influence of ethanol on the metabolism of alprazolam.

Expert Opin Drug Metab Toxicol 2018 Jun;14(6):551-559

a Department of Forensic Medicine, School of Basic Medical Sciences , Fudan University , Shanghai , China.

Background: Alprazolam is a commonly used benzodiazepine in clinical practice, and when coingested with ethanol, alprazolam can increase behavioral irritability and aggression. However, the mechanism of its interaction with ethanol remains unknown.

Research Design And Methods: The pharmacokinetics of alprazolam was studied in vivo in rat experiments involving the simultaneous administration of alprazolam and ethanol, and the interactions between ethanol and alprazolam were investigated in vitro in human liver microsomes. Read More

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http://dx.doi.org/10.1080/17425255.2018.1483338DOI Listing
June 2018
5 Reads

Benzodiazepine-refractory status epilepticus, neuroinflammation, and interneuron neurodegeneration after acute organophosphate intoxication.

Biochim Biophys Acta Mol Basis Dis 2018 09 23;1864(9 Pt B):2845-2858. Epub 2018 May 23.

Department of Neuroscience and Experimental Therapeutics, Texas A&M University Health Science Center, College of Medicine, Bryan, TX 77807, USA. Electronic address:

Nerve agents and some pesticides such as diisopropylfluorophosphate (DFP) cause neurotoxic manifestations that include seizures and status epilepticus (SE), which are potentially lethal and carry long-term neurological morbidity. Current antidotes for organophosphate (OP) intoxication include atropine, 2-PAM and diazepam (a benzodiazepine for treating seizures and SE). There is some evidence for partial or complete loss of diazepam anticonvulsant efficacy when given 30 min or later after exposure to an OP; this condition is known as refractory SE. Read More

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http://dx.doi.org/10.1016/j.bbadis.2018.05.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066461PMC
September 2018
12 Reads

Effects on the hepatic transcriptome of chicken embryos in ovo exposed to phenobarbital.

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

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http://dx.doi.org/10.1016/j.ecoenv.2018.05.033DOI Listing
September 2018
4 Reads

Hypoxic preconditioning reduces propofol-induced neuroapoptosis via regulation of Bcl-2 and Bax and downregulation of activated caspase-3 in the hippocampus of neonatal rats.

Neurol Res 2018 Sep 23;40(9):767-773. Epub 2018 May 23.

a Department of Anesthesiology , The First Affiliated Hospital of Guangxi Medical University , Nanning , China.

Objective:  Evidence has shown that propofol may cause widespread apoptotic neurodegeneration. Hypoxic preconditioning (HPC) was previously demonstrated to provide neuroprotection and brain recovery from either acute or chronic neurodegeneration in several cellular and animal models. Therefore, the present study was designed to investigate the protective effects of hypoxic preconditioning on apoptosis caused by propofol in neonatal rats. Read More

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http://dx.doi.org/10.1080/01616412.2018.1477545DOI Listing
September 2018
12 Reads

Beneficial Outcome of Urethane Treatment Following Status Epilepticus in a Rat Organophosphorus Toxicity Model.

eNeuro 2018 Mar-Apr;5(2). Epub 2018 Apr 17.

Department of Pharmacology, Emory University, Atlanta, GA 30322.

The efficacy of benzodiazepines to terminate electrographic status epilepticus (SE) declines the longer a patient is in SE. Therefore, alternative methods for ensuring complete block of SE and refractory SE are necessary. We compared the ability of diazepam and a subanesthetic dose of urethane to terminate prolonged SE and mitigate subsequent pathologies. Read More

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http://eneuro.org/lookup/doi/10.1523/ENEURO.0070-18.2018
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http://dx.doi.org/10.1523/ENEURO.0070-18.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952304PMC
January 2019
7 Reads

Differential sensitivity to the antifouling chemical medetomidine between wood frog and American toad tadpoles with evidence for low-dose stimulation and high-dose inhibition of metamorphosis.

Environ Sci Pollut Res Int 2018 Jul 5;25(20):19470-19479. Epub 2018 May 5.

Department of Biology, Gettysburg College, Gettysburg, PA, 17325, USA.

Antifouling chemicals are legacy contaminants in aquatic ecosystems. Previous experiments have shown that a 14-day exposure to the antifouling chemical medetomidine delays metamorphosis and reduces body mass in wood frog tadpoles. In the present study, we exposed wood frog tadpoles to medetomidine for 3, 7, and 10 days at 100 nM, 1 μM, and 10 μM. Read More

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http://dx.doi.org/10.1007/s11356-018-2168-yDOI Listing
July 2018
4 Reads

Midazolam Attenuates Autophagy and Apoptosis Caused by Ketamine by Decreasing Reactive Oxygen Species in the Hippocampus of Fetal Rats.

Neuroscience 2018 09 7;388:460-471. Epub 2018 Apr 7.

College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China. Electronic address:

Every year between 0.75% and 2% of pregnant women require surgery that is related to either the pregnancy or other medical problems in USA. Therefore, the neurodegeneration following anesthesia in a variety of animal models has attracted our attention. Read More

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http://dx.doi.org/10.1016/j.neuroscience.2018.03.040DOI Listing
September 2018
47 Reads

Propofol: a safe anaesthetic drug in experimental cardiac surgery in rabbits.

Ann Ital Chir 2018 ;89:92-94

Ackground: Experimental surgery needs a pharmacological approach that can interfere with cardiac function.

Case Report: In a animal model of regenerative medicine of myocardium we use an anaesthesiological protocol that included Propofol, a benzodiazepine (Midazolam) and an alpha-2 adrenergic agent.

Results: In a group of 15 rabbits undergoing cardiac surgery we reported 1 arrhythmic complication during stem cell injection. Read More

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November 2018
16 Reads

Cytochrome P450-dependent drug oxidation activities in commercially available hepatocytes derived from human induced pluripotent stem cells cultured for 3 weeks.

J Toxicol Sci 2018 ;43(4):241-245

Hepatocyte-like cells differentiated from human induced pluripotent stem (iPS) cells are of great interest for applications in pharmacological research. For drug metabolism testing, commercially available hepatocytes derived from human iPS cells are generally recommended to be used 1 week after seeding on plates. In this study, however, after 3-4 weeks of culture according to the manufacturer's instructions, human cytochrome P450 (P450) 2C9- and 2C19-dependent diclofenac 4'-hydroxylation and omeprazole 5-hydroxylation activities of the iPS-derived hepatocytes had significantly increased above the activities at 1 week and had reached levels similar to those in HepaRG cells, a human hepatocyte-like cell line. Read More

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http://dx.doi.org/10.2131/jts.43.241DOI Listing
August 2018
8 Reads

The antihistamine diphenhydramine is demethylated by anaerobic wastewater microorganisms.

Chemosphere 2018 Jul 15;202:460-466. Epub 2018 Mar 15.

Department of Environmental Sciences, Rutgers University, 59 Dudley Road, New Brunswick, NJ 08901, USA. Electronic address:

While emerging pharmaceutical contaminants are monitored in wastewater treatment and the environment, there is little information concerning their microbial metabolites. The transformation of diphenhydramine by microorganisms in anaerobic digester sludge was investigated using anaerobic cultures amended with 1 mM diphenhydramine as the sole carbon source. Complete transformation of the parent compound to a persistent metabolite occurred within 191 days. Read More

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http://dx.doi.org/10.1016/j.chemosphere.2018.03.093DOI Listing
July 2018
4 Reads
3.340 Impact Factor

Inhibition of microRNA-34a protects against propofol anesthesia-induced neurotoxicity and cognitive dysfunction via the MAPK/ERK signaling pathway.

Neurosci Lett 2018 05 22;675:152-159. Epub 2018 Mar 22.

Department of Pharmacy, Linyi Central Hospital, Linyi, Shandong, China. Electronic address:

Aim: To investigate the protective effect of microRNA-34a (miR-34a) on propofol-induced neurotoxicity and cognitive dysfunction.

Methods: After SH-SY5Y cells were treated with propofol to induce neurotoxicity, microRNA-34a mimics and inhibitors were transfected into the cells. The expression of apoptosis-related genes and the proteins were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. Read More

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http://dx.doi.org/10.1016/j.neulet.2018.03.052DOI Listing
May 2018
4 Reads

Effects of isopentyl ferulate on oxidative stress biomarkers and a possible GABAergic anxiolytic-like trait in Swiss mice.

Chem Biol Interact 2018 Jun 20;289:119-128. Epub 2018 Mar 20.

Postgraduate Program in Pharmacology, Federal University of Piauí, Teresina, Piauí, 64.049-550, Brazil; Laboratory of Research in Experimental Neurochemistry of Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Piauí, 64.049-550, Brazil.

This study aimed to evaluate the anxiolytic-like effect and the possible neuronal mechanism of action of isopentyl ferulate (IF). For this purpose, we used the marble burying test in Swiss albino mice. The biomarkers involved in oxidative stress were measured in the hippocampus homogenate of the test animals. Read More

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http://dx.doi.org/10.1016/j.cbi.2018.03.009DOI Listing
June 2018
7 Reads

Non-sedation of the neonate for radiologic procedures.

Authors:
Richard B Parad

Pediatr Radiol 2018 04 17;48(4):524-530. Epub 2018 Mar 17.

Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, 75 Francis St., Rm. CWN418, Boston, MA, 02115, USA.

On Dec. 16, 2016, the U.S. Read More

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http://dx.doi.org/10.1007/s00247-017-4002-yDOI Listing
April 2018
5 Reads