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https://www.readbyqxmd.com/read/29148295/is-naloxone-the-best-antidote-to-reverse-tramadol-induced-neuro-respiratory-toxicity-in-overdose-an-experimental-investigation-in-the-rat
#1
Camille Lagard, Isabelle Malissin, Wassila Indja, Patricia Risède, Lucie Chevillard, Bruno Mégarbane
CONTEXT: Since the banning of dextropropoxyphene from the market, overdoses, and fatalities attributed to tramadol, a WHO step-2 opioid analgesic, have increased markedly. Tramadol overdose results not only in central nervous system (CNS) depression attributed to its opioid properties but also in seizures, possibly related to non-opioidergic pathways, thus questioning the efficiency of naloxone to reverse tramadol-induced CNS toxicity. OBJECTIVE: To investigate the most efficient antidote to reverse tramadol-induced seizures and respiratory depression in overdose...
November 17, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/29138471/%C3%AE-subunits-in-gabaa-receptors-are-dispensable-for-gaba-and-diazepam-action
#2
Nisa Wongsamitkul, Maria C Maldifassi, Xenia Simeone, Roland Baur, Margot Ernst, Erwin Sigel
The major isoform of the GABAA receptor is α1β2γ2. The binding sites for the agonist GABA are located at the β2+/α1- subunit interfaces and the modulatory site for benzodiazepines at α1+/γ2-. In the absence of α1 subunits, a receptor was formed that was gated by GABA and modulated by diazepam similarly. This indicates that alternative subunits can take over the role of the α1 subunits. Point mutations were introduced in β2 or γ2 subunits at positions homologous to α1- benzodiazepine binding and GABA binding positions, respectively...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29136575/the-correlation-between-concentrations-of-zolpidem-and-benzodiazepines-in-segmental-hair-samples-and-use-patterns
#3
Hyojeong Kim, Sangeun Lee, Sanghwan In, Meejung Park, Sungnam Cho, Junguk Shin, Hunjoo Lee, Eunyoung Han
The aim of this study was to investigate the correlation between histories of zolpidem and benzodiazepines use and their concentrations in hair as determined by segmental hair analysis, that is, by analyzing hair samples taken 0-1, 1-2, 2-3, 3-4, 4-5, and 5-6cm etc. and 0-3cm from the scalp, and whole hair. Of the 23 hair samples examined, 18 were collected from patients in a rehabilitation program and five were from patients that had taken zolpidem only once by prescription. All 23 patients provided written informed consent after reviewing the research plan, described their zolpidem and benzodiazepines use histories accurately, and provided hair samples, which were weighed, washed, cut into lengths of <1mm, and extracted in 100% methanol for 16h (diazepam-d5 was used as an internal standard)...
November 7, 2017: Forensic Science International
https://www.readbyqxmd.com/read/29135112/symptom-triggered-alcohol-vapor-inhalation-for-postoperative-alcohol-withdrawal-syndrome-in-patients-with-gastroesophageal-carcinoma
#4
Fengwei Kong, Miao Zhang, Heng Wang, Dong Liu, Ying Wu, Ning Chai, Wenbin Wu
PURPOSE: The purpose of this study was to investigate the feasibility and efficacy of alcohol vapor inhalation during fasting time for cancer patients with alcohol withdrawal symptoms (AWS) after surgery. METHODS: The data of 51 patients after esophagectomy or gastrectomy for gastroesophageal carcinoma in two hospitals from January 2011 to December 2016 was retrospectively analyzed. These patients were diagnosed with AWS with Clinic Institute Alcohol Withdrawal Syndrome Scale (CIWA-Ar) score ≥ 9 in two hospitals during fasting time from January 2011 to December 2016, and they were accordingly divided into alcohol vapor group (n=25) and diazepam group (n=26)...
September 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29131354/effect-of-status-epilepticus-on-expression-of-brain-udp-glucuronosyltransferase-1a-in-rats
#5
Yuki Asai, Hatsuna Tanaka, Masayuki Nadai, Miki Katoh
Status epilepticus (SE) involves severe epileptic seizures that cause oxidative stress in the brain. Oxidative stress is known to influence uridine 5'-diposphate-glucuronosyltransferase (UGT) 1A expression. The present study aimed at elucidating the effect of SE on Ugt1a1, Ugt1a6, and Ugt1a7 expression in the rat brain. Kainic acid was used to create an animal model of SE. Sprague-Dawley rats were treated intraperitoneally with 10 mg/kg kainic acid. Ugt1a1 and Ugt1a7 mRNA levels were increased by SE in the cortex and hippocampus (Ugt1a1: 4...
November 13, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29131129/effect-of-diazepam-on-24-hour-blood-pressure-and-heart-rate-in-healthy-young-volunteers
#6
Alfredo Costa, Daniele Bosone, Annalisa Zoppi, Angela D Apos Angelo, Natascia Ghiotto, Elena Guaschino, Matteo Cotta Ramusino, Roberto Fogari
AIM: To assess the effects of evening chronic administration of diazepam on 24-h blood pressure (BP) and heart rate (HR) in healthy young adults. METHODS: This randomized double blind, cross-over study evaluated the effects of diazepam 5 mg or placebo, both ingested in the evening, on 24-h ambulatory BP and HR in healthy subjects aged 21-30. RESULTS: A total of 30 subjects were included in the analysis. At the end of 4-week diazepam intake, an increase in 24-h HR mean values was found (+5...
October 31, 2017: Pharmacology
https://www.readbyqxmd.com/read/29129798/the-efficacy-of-hi-6-dms-in-a-sustained-infusion-against-percutaneous-vx-poisoning-in-the-guinea-pig
#7
C Whitmore, A R Cook, T Mann, M E Price, E Emery, N Roughley, D Flint, S Stubbs, S J Armstrong, H Rice, J E H Tattersall
Post-exposure nerve agent treatment usually includes administration of an oxime, which acts to restore function of the enzyme acetylcholinesterase (AChE). For immediate treatment of military personnel, this is usually administered with an autoinjector device, or devices containing the oxime such as pralidoxime, atropine and diazepam. In addition to the autoinjector, it is likely that personnel exposed to nerve agents, particularly by the percutaneous route, will require further treatment at medical facilities...
November 9, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29128746/human-serum-albumin-binding-of-certain-antimalarials
#8
Olivera S Marković, Ilija N Cvijetić, Mario V Zlatović, Igor M Opsenica, Jelena M Konstantinović, Nataša V Terzić Jovanović, Bogdan A Šolaja, Tatjana Ž Verbić
Interactions between eight in-house synthesized aminoquinolines, along with well-known chloroquine, and human serum albumin (HSA) have been studied by fluorescence spectroscopy. The synthesized aminoquinolines, despite being structurally diverse, were found to be very potent antimalarials. Fluorescence measurements indicate that three compounds having additional thiophene or benzothiophene substructure bind more strongly to HSA than other studied compounds. Competitive binding experiments indicate that these three compounds bind significantly stronger to warfarin compared to diazepam binding site...
November 9, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/29128652/differences-in-combinations-and-concentrations-of-drugs-of-abuse-in-fatal-intoxication-and-driving-under-the-influence-cases
#9
Hilde Erøy Edvardsen, Torill Tverborgvik, Joachim Frost, Sidsel Rogde, Inge Morild, Helge Waal, Thomas Clausen, Lars Slørdal, Vigdis Vindenes
BACKGROUND: In toxicology, international classification systems focus on single intoxicants as the cause of death. It is, however, well known that very few drug related deaths are caused by a single substance and that information concerning the drug concentrations as well as the combinations of drugs are essential in order to ascertain the cause of death. The aim of the study was to assess whether those prone to fatal intoxications differ significantly from chronic drug users - in terms of demographics and drug exposure patterns...
November 6, 2017: Forensic Science International
https://www.readbyqxmd.com/read/29128277/a-fast-sensitive-and-high-throughput-method-for-the-determination-of-esomeprazole-in-dog-plasma-by-uhplc-ms-ms-application-to-formulation-development-of-the-compound-preparation-of-esomeprazole
#10
Ran Liu, Pei Li, Jie Xiao, Yidi Yin, Zheng Sun, Kaishun Bi, Qing Li
To investigate deeply into the preclinical pharmacokinetics and prescription design of esomeprazole, a sensitive, high throughput and robust UHPLC-MS/MS method had been developed and fully validated for the analysis of esomeprazole in dog plasma. Esomeprazole and diazepam (IS) were fast extracted from plasma by alkalified organic solvent, and separated on MP-C18 column with methanol and 0.1% formic acid. The quantification of esomeprazole and IS had been achieved using fragmentation transitions of m/z 346.1→198...
November 4, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29127295/clinical-potential-of-an-enzyme-based-novel-therapy-for-cocaine-overdose
#11
Ting Zhang, Xirong Zheng, Ziyuan Zhou, Xiabin Chen, Zhenyu Jin, Jing Deng, Chang-Guo Zhan, Fang Zheng
It is a grand challenge to develop a truly effective medication for treatment of cocaine overdose. The current available, practical emergence treatment for cocaine overdose includes administration of a benzodiazepine anticonvulsant agent (e.g. diazepam) and/or physical cooling with an aim to relieve the symptoms. The inherent difficulties of antagonizing physiological effects of drugs in the central nervous system have led to exploring protein-based pharmacokinetic approaches using biologics like vaccines, monoclonal antibodies, and enzymes...
November 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29119924/deaths-in-the-lesbian-gay-bisexual-and-transgender-united-kingdom-communities-associated-with-ghb-and-precursors
#12
John M Corkery, Barbara Loi, Hugh Claridge, Christine Goodair, Fabrizio Schifano
Background Misuse of gammahydroxybutrate (GHB) and its prodrugs gammabutyrolactone (GBL) and 1,4 butanediol (1,4-BD) has increased greatly since the early 1990s, particularly amongst lesbian, gay, bisexual and transgender (LGBT) individuals in recreational and sexual settings, e.g. 'chemsex'. Objective and method This paper presents an overview of GHB pharmacotoxicology and provides analyses of cases in the LGBT population associated with use of these substances extracted from the UK's National Programme on Substance Abuse Deaths database, to which notification is voluntary...
November 8, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/29111406/panic-like-escape-response-elicited-in-mice-by-exposure-to-co2-but-not-hypoxia
#13
Ailton Spiacci, Heloisa H Vilela-Costa, Ana Beatriz Sant'Ana, Gabriel Gripp Fernandes, Alana Tercino Frias, Glauber S Ferreira da Silva, José Antunes-Rodrigues, Hélio Zangrossi
Exposure to elevated concentrations of CO2 or hypoxia has been widely used in psychiatric research as a panic provoking stimulus. However, the use of these respiratory challenges to model panic-like responses in experimental animals has been less straightforward. Little data is available, from behavioral and endocrine perspectives, to support the conclusion that a marked aversive situation, such as that experienced during panic attacks, was evoked in these animals. We here compared the behavioral responses of male CB57BL/6 mice during exposure to 20% CO2 or 7% O2 and its consequence on plasma levels of corticosterone...
October 28, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29105865/oral-medication-prescription-practices-of-tertiary-based-specialists-for-dystonia-in-children-with-cerebral-palsy
#14
Adrienne Harvey, Dinah Reddihough, Adam Scheinberg, Katrina Williams
AIM: To examine current clinical practice for prescribing medications for children with dystonic cerebral palsy (CP) by medical doctors working at a tertiary care centre. METHODS: Rehabilitation and developmental paediatric specialists completed: (i) a custom-designed online cross-sectional survey capturing their usual prescribing patterns; and (ii) one-page questionnaires detailing medication prescription for each child with CP who they started on a new medication for dystonia over a 12-month period...
November 6, 2017: Journal of Paediatrics and Child Health
https://www.readbyqxmd.com/read/29105206/risk-factors-for-psychological-and-psychosomatic-symptoms-among-children-with-malignancies
#15
Kenichi Maeda, Daisuke Hasegawa, Kevin Y Urayama, Shinichi Tsujimoto, Yuriko Azami, Miwa Ozawa, Atsushi Manabe
AIM: With increasing survival rates in paediatric malignancies, the quality-of-life of children during hospitalisation should be given more attention. We aimed to identify factors associated with psychological and psychosomatic symptoms (PPS) that required medication among children hospitalised for treatment of malignancies. METHODS: We retrospectively analysed data of 190 patients aged 2-18 years old. They were diagnosed with malignant diseases and admitted for treatment at St...
November 3, 2017: Journal of Paediatrics and Child Health
https://www.readbyqxmd.com/read/29104261/neurochemical-changes-and-c-fos-mapping-in-the-brain-after-carisbamate-treatment-of-rats-subjected-to-lithium-pilocarpine-induced-status-epilepticus
#16
José Eduardo Marques-Carneiro, Astrid Nehlig, Jean-Christophe Cassel, Eduardo Ferreira Castro-Neto, Julia Julie Litzahn, Anne Pereira de Vasconcelos, Maria da Graça Naffah-Mazacoratti, Maria José da Silva Fernandes
The administration of lithium-pilocarpine (LiPilo) in adult rats is a validated model reproducing the main clinical and neuropathological features of temporal lobe epilepsy (TLE). Previous studies have shown that carisbamate (CRS) has the property of modifying epileptogenesis in this model. When treated with CRS, about 50% of rats undergoing LiPilo status epilepticus (SE) develop non-convulsive seizures (NCS) instead of convulsive ones (commonly observed in TLE). The goal of this work was to determine some of the early changes that occur after CRS administration, as they could be involved in the insult- and epileptogenesis-modifying effects of CRS...
November 1, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/29101905/conversion-factors-for-assessment-of-driving-impairment-after-exposure-to-multiple-benzodiazepines-z-hypnotics-or-opioids
#17
Maren Cecilie Strand, Jørg Mørland, Lars Slørdal, Bettina Riedel, Cato Innerdal, Trond Aamo, Grete Mathisrud, Vigdis Vindenes
AIMS: Norway has introduced legal concentration limits in blood for 28 non-alcohol drugs in driving under the influence cases. As of 2016 this legislation also regulates the assessment of combined effects of multiple benzodiazepines and opioids. We herein describe the employed methodology for the equivalence tables for concentrations of benzodiazepines/z-hypnotics and opioids implemented in the Norwegian Road Traffic Act. METHODS: Legislative limits corresponding to impairment at blood alcohol concentrations (BAC) of 0...
October 20, 2017: Forensic Science International
https://www.readbyqxmd.com/read/29098059/curcumin-reverses-the-diazepam-induced-cognitive-impairment-by-modulation-of-oxidative-stress-and-erk-1-2-nf-%C3%AE%C2%BAb-pathway-in-brain
#18
Alexandra C Sevastre-Berghian, Vlad Făgărăsan, Vlad A Toma, Ioana Bâldea, Diana Olteanu, Remus Moldovan, Nicoleta Decea, Gabriela A Filip, Simona V Clichici
Oxidative stress and inflammation can be involved in cognitive dysfunction associated with neurodegenerative disorders. Diazepam (DZP) administration has been chosen to simulate the memory impairment. The aim of this study was to evaluate the effects of curcumin (CUR) on spatial cognition, ambulatory activity, and blood and brain oxidative stress levels. The ERK/NF-κB signaling pathway and the histopathological changes in the hippocampus and frontal lobe, in diazepam-treated rats, were also analyzed. The animals were divided into 4 groups: control, carboxymethylcellulose (CMC) + CUR, CMC + DZP, and CUR + CMC + DZP...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29097142/exploring-the-feasibility-of-the-use-of-biopolymers-as-a-carrier-in-the-formulation-of-amorphous-solid-dispersions-part-i-gelatin
#19
Timothy Pas, Bjorn Vergauwen, Guy Van den Mooter
Biopolymers have rarely been used so far as carriers in the formulation of amorphous solid dispersions (ASD) to overcome poor solubility of active pharmaceutical ingredients (APIs). In an attempt to enlarge our knowledge on this topic, gelatin, type 50PS was selected. A screening study was initiated in which twelve structurally different poorly soluble biopharmaceutical classification system (BCS) Class II drugs (carbamazepine, cinnarizine, diazepam, itraconazole, nifedipine, indomethacin, darunavir (ethanolate), ritonavir, fenofibrate, griseofulvin, ketoconazole and naproxen) were selected for evaluation...
October 31, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29096991/intox-detox-antidotes-evidence-based-diagnosis-and-treatment-of-acute-intoxications
#20
Andreas Schaper, Martin Ebbecke
BACKGROUND AND AIM: Aim of this review is to describe the role of clinical toxicology in the context of acute medicine. A special focus is put on antidotes and important aspects of diagnosis and therapy of acute intoxications. The data of the annual report of GIZ-Nord Poisons Centre is analyzed concerning the following aspects: what intoxications are relevant in acute medicine, are there special aspects in therapy, e.g. antidotes, and what antidotes are relevant? More over intoxication-related fatalities are analyzed...
October 30, 2017: European Journal of Internal Medicine
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