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Jennifer L Pilgrim, Rhyse Dorward, Olaf H Drummer
BACKGROUND AND AIMS: There are numerous factors putting health-care professionals (HCP) at a higher risk of substance abuse and premature death, including high-stress jobs, access to controlled substances, long hours of practice and constant contact with the critically ill. This study aimed to examine fatal drug toxicity in this high-risk cohort, in order to: (1) estimate the rate of drug-caused deaths of Australian HCPs; (2) describe the key characteristics of the cohort; and (3) examine the relationship between HCP occupation and drug type, or intent...
November 20, 2016: Addiction
Zubair A Ahmed, Dimitrios A Nacopoulos, Seby John, Nancy Papesh, David Levine, Cynthia C Bamford
OBJECTIVE: To develop and implement an algorithm for the management of headaches presenting to the emergency department (ED) in order to decrease the frequency of opioid and barbiturate treatment both acutely as well as on discharge. BACKGROUND: Headache is the fifth leading cause of ED visits in the United States. In the case of primary headache, particularly migraine, treatment in the ED can be highly variable. Patients with migraine continue to be treated with opioids more commonly than nonopioid, migraine specific medications...
November 10, 2016: Headache
Hyun Mook Kwon, Jin Wook Baek, Sang Pyung Lee, Jae Ik Cho
The management guideline for traumatic brain injury (TBI) recommends high-dose barbiturate therapy to control increased intracranial pressure refractory to other therapeutic options. High-dose barbiturate therapy, however, may cause many severe side effects; the commonly recognized ones include hypotension, immunosuppression, hepatic dysfunction, renal dysfunction, and prolonged decrease of cortical activity. Meanwhile, dyskalemia remains relatively uncommon. In this study, we report the case of a hypokalemic patient with severe rebound hyperkalemia, which occurred as a result of barbiturate coma therapy administered for TBI treatment...
October 2016: Korean Journal of Neurotrauma
Anshuman Singh, Anita Agrahari, RadhaDutt Singh, Sanjay Yadav, Vikas Srivastava, Devendra Parmar
Epigenetic studies were carried in the rat offsprings, born to dams treated with cypermethrin (orally; 5.0 mg/kg) from gestation day (GD) 5 to 21 and rechallenged with cypermethrin (orally; 10 mg/kg for 6 days), at adulthood (12 weeks) to understand the mechanism underlying the overexpression of cerebral cytochrome P450s (CYPs) in exposed offsprings. The data revealed alterations in histone H3 acetylation and DNA methylation in promoter regions of CYP1A- and 2B- isoenzymes in the brain isolated from rechallenged animals...
November 17, 2016: Scientific Reports
Satoshi Hori, Kosaku Kinoshita
OBJECTIVE: The purpose of this study was to identify the clinical aspects leading to overdose of multiple psychotropic drugs, in order to determine areas which need attention in the proper treatment of overdose patients. METHODS: Patients who were treated for overdose of psychotropic drugs at our emergency and critical center over two years were targeted. The clinical data was gathered from the medical records and database of all patients, including age, gender, vital signs, and laboratory data, drugs, and medical complications during hospital stay...
2016: Journal of Toxicological Sciences
S F Chavoushi, L Mesman, P G Noordzij, M A Sikma, E M van Maarseveen
BACKGROUND: Barbiturate intoxication is potentially lethal. With the availability of the newer anticonvulsants the use of barbiturates in treating epilepsy has decreased significantly, with a concurrent decrease in the incidence of overdose with these medications. There have, however, been recent alarm signals from governmental sources concerning the increase in the Internet purchase of illegal medications, including barbiturates, for use in attempted suicide. CASE DESCRIPTION: Here we describe two patient cases involving barbiturate intoxication with amobarbital and thiopental, respectively...
2016: Nederlands Tijdschrift Voor Geneeskunde
Saganuwan Alhaji Saganuwan
Piroxicam has been reported to be convertible to central nervous system (CNS) acting agents. It has serious depressant effects at high doses. In view of this structures of piroxicam metabolites were assessed for possible conversion to CNS depressants. Structural barbituric compounds, carboxamide, cyclohydrated, benzothiazone and carboxybenzothiazone metabolites which may act via dopamine and adrenergic receptors causing depression of CNS activities.
November 10, 2016: Central Nervous System Agents in Medicinal Chemistry
David C Chiara, Youssef Jounaidi, Xiaojuan Zhou, Pavel Y Savechenkov, Karol S Bruzik, Keith W Miller, Jonathan B Cohen
Extra-synaptic γ-aminobutyric acid type A receptors (GABAAR), which contribute generalized inhibitory tone to the mammalian brain, are major targets for general anesthetics. To identify anesthetic binding sites in an extra-synaptic GABAAR, we photolabeled human α4β3δ GABAARs purified in detergent with [3H]azietomidate and a barbiturate, [3H]R-mTFD-MPAB, photoreactive anesthetics that bind with high selectivity to distinct but homologous intersubunit binding sites in the transmembrane domain of synaptic α1β3γ2 GABAARs...
November 7, 2016: Journal of Biological Chemistry
Agnieszka Ambrożak, Christian Steinebach, Erin R Gardner, Shaunna L Beedie, Gregor Schnakenburg, William D Figg, Michael Gütschow
The development of novel thalidomide derivatives as immunomodulatory and anti-angiogenic agents has revived over the last two decades. Herein we report the design and synthesis of three chemotypes of barbituric acids derived from the thalidomide structure: phthalimido-, tetrafluorophthalimido-, and tetrafluorobenzamidobarbituric acids. The latter were obtained by a new tandem reaction, including a ring opening and a decarboxylation of the fluorine-activated phthalamic acid intermediates. Thirty compounds of the three chemotypes were evaluated for their anti-angiogenic properties in an ex vivo assay by measuring the decrease in microvessel outgrowth in rat aortic ring explants...
November 2, 2016: ChemMedChem
Toshiyasu Mikuma, Ryo Uchida, Mizuki Kajiya, Yuki Hiruta, Hideko Kanazawa
A novel pretreatment method, which was performed using a two-dimensional high-performance liquid chromatography (2D-HPLC) system, was proposed for the direct analysis of drugs in human serum. A temperature-responsive column was used as a pretreatment column. The stationary phase of the temperature-responsive column exhibits temperature-regulated hydrophilic/hydrophobic characteristics. Controlling the ionic strength of the eluent enables human serum albumin (HSA) to pass through the column without retention...
October 29, 2016: Analytical and Bioanalytical Chemistry
Andresa H Betti, Camila B Antonio, Thais E T Pompeu, Thaise S Martins, Vivian Herzfeldt, Eveline D Stolz, Carlos A M Fraga, Eliezer Barreiro, François Noël, Stela M K Rates
Aiming to identify new antipsychotic lead-compounds, our group has been working on the design and synthesis of new N-phenylpiperazine derivatives. Here, we characterized LASSBio-1422 as a pharmacological prototype of this chemical series. Adult male Wistar rats and CF1 mice were used for in-vitro and in-vivo assays, respectively. LASSBio-1422 [1 and 5 mg/kg, postoperatively (p.o.)] inhibited apomorphine-induced climbing as well as ketamine-induced hyperlocomotion (1 and 5 mg/kg, p.o.), animal models predictive of efficacy on positive symptoms...
October 13, 2016: Behavioural Pharmacology
Anahita Nourmahnad, Alex T Stern, Mayo Hotta, Deirdre S Stewart, Alexis M Ziemba, Andrea Szabo, Stuart A Forman
BACKGROUND: γ-Aminobutyric acid type A (GABAA) receptors mediate important effects of intravenous general anesthetics. Photolabel derivatives of etomidate, propofol, barbiturates, and a neurosteroid get incorporated in GABAA receptor transmembrane helices M1 and M3 adjacent to intersubunit pockets. However, photolabels have not been consistently targeted at heteromeric αβγ receptors and do not form adducts with all contact residues. Complementary approaches may further define anesthetic sites in typical GABAA receptors...
December 2016: Anesthesiology
Eric Fillion, Azadeh Kavoosi, Kevin Nguyen, Christian Ieritano
Tris(pentafluorophenyl)borane, B(C6F5)3, has been found to be an effective catalyst to access the hydridoborate anion, [N(CH2CH2CH2)3Sn][HB(C6F5)3], via hydride abstraction from the hypercoordinated tin reagent, iPr-tricarbastannatrane. This process has been applied to the B(C6F5)3-catalyzed transfer 1,4-hydrostannylation of electron-deficient olefins, namely benzylidene barbituric acids. Insights into the mechanism have been obtained via a series of (1)H, (2)H, (11)B, (13)C, and (119)Sn NMR spectroscopy, mass spectrometry, and labeling experiments...
October 12, 2016: Chemical Communications: Chem Comm
O Shemchuk, D Braga, F Grepioni
Alloying isomorphous crystals of barbituric acid (BA) and thiobarbituric acid (TBA) yields solid solutions of general formula BAxTBA1-x (x < 0.8); for x = 0.5 the stable co-crystal BA0.5TBA0.5, isomorphous with the parent keto forms, is observed, which melts at 265 °C, i.e. ca. 10 and 20 °C higher than the melting points of BA and TBA, respectively. While the BAxTBA1-x solid solutions with x > 0.5 are stable, those with x < 0.5 convert, with time or temperature, to the BA0.5TBA0.5 co-crystal.
September 27, 2016: Chemical Communications: Chem Comm
Keith L Shelton
Inhalants are a loosely organized category of abused compounds defined entirely by their common route of administration. Inhalants include volatile solvents, fuels, volatile anesthetics, gasses, and liquefied refrigerants, among others. They are ubiquitous in modern society as ingredients in a wide variety of household, commercial, and medical products. Persons of all ages abuse inhalants but the highest prevalence of abuse is in younger adolescents. Although inhalants have been shown to act upon a host of neurotransmitter receptors, the stimulus effects of the few inhalants which have been trained or tested in drug discrimination procedures suggest that their discriminative stimulus properties are mediated by a few key neurotransmitter receptor systems...
October 7, 2016: Current Topics in Behavioral Neurosciences
James R Hemmer, Saemi O Poelma, Nicolas Treat, Zachariah A Page, Neil Dolinski, Yvonne J Diaz, Warren Tomlinson, Kyle D Clark, Joseph P Hooper, Craig J Hawker, Javier Read de Alaniz
A class of tunable visible and near-infrared donor-acceptor Stenhouse adduct (DASA) photoswitches were efficiently synthesized in 2 to 4 steps from commercially available starting materials with minimal purification. Using either Meldrum's or barbituric acid "acceptors" in combination with aniline-based "donors" an absorption range spanning from 450 to 750 nm is obtained. Additionally, photoisomerization results in complete decoloration for all adducts, yielding fully transparent, colorless solutions and films...
October 4, 2016: Journal of the American Chemical Society
Christopher R Newey, Dolora Wisco, Premkumar Nattanmai, Aarti Sarwal
BACKGROUND: Refractory status epilepticus is often treated with third-line therapy, such as pentobarbital coma. However, its use is limited by side effects. Recognizing and preventing major and minor adverse effects of prolonged pentobarbital coma may increase good outcomes. This study retrospectively reviewed direct and indirect medical and surgical pentobarbital coma. METHODS: Retrospective chart review of all patients with refractory status epilepticus treated with pentobarbital over a 1 year period at a large tertiary care center...
October 2016: Therapeutic Advances in Drug Safety
Michele Fiore, Peter Strazewski
There may be more than one way leading to RNA: Recent discoveries in the synthesis of nucleoside and nucleotide precursors are described and put into the wider context of prebiotic systems chemistry. Mixing Butlerow's carbohydrate precursors with Traube's 5-formylaminopyrimidines has led to the formation of prebiotic purine nucleosides whereas the mixing of 5-phosphoribose with barbituric acid and melamine gave supramolecular fibers from stacks of Whitesides' rosettas.
September 15, 2016: Angewandte Chemie
Xiaonan Sun, Fabien Silly, Francois Maurel, Changzhi Dong
Barbituric acid derivatives are prochiral molecules, i.e. they are chiral upon adsorption on surfaces. Scanning tunneling microscopy reveals that barbituric acid derivatives self-assemble into a chiral guest-host supramolecular architecture at the solid-liquid interface on graphite. The host nanoarchitecture has a sophisticated wavy shape pattern and paired guest molecules are nested insides the cavities of the host structure. Each unit cell of the host structure is composed of both enantiomers with a ratio of 1:1...
October 21, 2016: Nanotechnology
Amber L Bahorik, Derek D Satre, Andrea H Kline-Simon, Constance M Weisner, Cynthia I Campbell
OBJECTIVES: We examined prevalence of major medical conditions and extent of disease burden among patients with and without substance use disorders (SUDs) in an integrated health care system serving 3.8 million members. METHODS: Medical conditions and SUDs were extracted from electronic health records in 2010. Patients with SUDs (n = 45,461; alcohol, amphetamine, barbiturate, cocaine, hallucinogen, and opioid) and demographically matched patients without SUDs (n = 45,461) were compared on the prevalence of 19 major medical conditions...
September 8, 2016: Journal of Addiction Medicine
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