Sample records for barbiturates

  1. Extracorporeal treatment for barbiturate poisoning

    DEFF Research Database (Denmark)

    Mactier, Robert; Laliberté, Martin; Mardini, Joelle


    The EXTRIP (Extracorporeal Treatments in Poisoning) Workgroup conducted a systematic review of barbiturate poisoning using a standardized evidence-based process to provide recommendations on the use of extracorporeal treatment (ECTR) in patients with barbiturate poisoning. The authors reviewed all...... articles, extracted data, summarized key findings, and proposed structured voting statements following a predetermined format. A 2-round modified Delphi method was used to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. 617 articles met......-acting barbiturates are dialyzable and short-acting barbiturates are moderately dialyzable. Four key recommendations were made. (1) The use of ECTR should be restricted to cases of severe long-acting barbiturate poisoning. (2) The indications for ECTR in this setting are the presence of prolonged coma, respiratory...

  2. Barbiturate-refractory epilepsy: safe schedule for therapeutic substitution


    Gorz, Ana Maria; Silvado, Carlos E. S.; Bittencourt, Paulo Rogério M.


    Barbiturates are considered first line antiepileptic drugs in third world countries due to traditional and economic reasons. This prospective uncontrolled study of 52 patients aged 15 to 64 years (mean 24) demonstrates that patients who become refractory to barbiturates are mainly those with partial seizures with or without generalization or with a focal EEG abnormality (71%). Seizures tend to become refractory approximately 6 years after barbiturates were started. Progressive barbiturate wit...

  3. Formation of a hydrogen-bonded barbiturate [2]-rotaxane. (United States)

    Tron, Arnaud; Thornton, Peter J; Rocher, Mathias; Jacquot de Rouville, Henri-Pierre; Desvergne, Jean-Pierre; Kauffmann, Brice; Buffeteau, Thierry; Cavagnat, Dominique; Tucker, James H R; McClenaghan, Nathan D


    Interlocked structures containing the classic Hamilton barbiturate binding motif comprising two 2,6-diamidopyridine units are reported for the first time. Stable [2]-rotaxanes can be accessed either through hydrogen-bonded preorganization by a barbiturate thread followed by a Cu(+)-catalyzed "click" stoppering reaction or by a Cu(2+)-mediated Glaser homocoupling reaction.

  4. new spiro (thio) barbiturates based on cyclohexanone and bicyclo

    African Journals Online (AJOL)

    Preferred Customer

    condensation can be operated with the aid of strong acids or bases [2, 13]. Several catalytic methods have been achieved for crossed-aldol condensation [4, 14-31]. Several spiro-(thio)barbituric acid derivatives in which the active methylene carbon of. (thio)barbituric acid is substituted by an unsubstituted cyclobutane or ...


    Directory of Open Access Journals (Sweden)

    T. V. Koksharova


    Full Text Available The various aspects of the 3d-metal complexes with barbiturates and uric acid chemistry such as composition, structure, physicochemical properties, possible fields of application – have been illustrated in this review

  6. Synthesis of carboranyl amino acids, hydantoins, and barbiturates

    International Nuclear Information System (INIS)

    Wyzlic, I.M.; Tjarks, W.; Soloway, A.H.


    The syntheses of three novel boronated hydantoins, 5-(o-carboran-1-ylmethyl)hydantoin, 14, the tetraphenylphosphonium salt of 7-(hydantoin-5-ylmethyl)dodecahydro-7,8-dicarba-nido-undecaborate, 15, 5-(o-carboran-1-ylmethyl)-2-thiohydantoin, 16, and two new barbiturates, 5,5-bis(but-2-ynyl)barbiturate, 18, and 5,5-bis[(2-methyl-0-carboran-1-yl)methyl]barbiturate, 20, are described. Hydantoins 14-16 were synthesized from o-carboranylalanine (Car, 13). The detailed synthesis of Car and two other carborane-containing amino acids, O-(o-carboran-1-ylmethyl)tyrosine (CBT, 5a) and p-(o-carboran-1-yl)phenylalanine (CBPA, 5b), presented earlier as a communication, 16 are also described. Hydantoin 14 and barbiturates 18 and 20 were tested for their potential anticonvulsant activity. Initial qualitative screening showed moderate activities for hydantoin 14 and barbiturate 18. Barbiturate 20 had no activity. Compound 14 appeared to be nontoxic at doses of 300 mg/kg (mice, ip) and 50 mg/kg (rats, oral). However, 18 was very toxic under similar conditions

  7. Severe cutaneous reactions caused by barbiturates in seven Iranian children. (United States)

    Mamishi, Setareh; Fattahi, Fatemeh; Pourpak, Zahra; Aghaee, Farzaneh Mirza; Moinfar, Zeinab; Mohammadi, Mahmoud; Ashrafi, Mahmoud; Moin, Mostafa


    The severe adverse cutaneous reactions of erythema multiforme (EM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare mucocutaneous diseases associated with significant morbidity and mortality. The most common cause is antiepileptic drugs, particularly carbamazepine and lamotrigine, as well as the barbiturates group (phenobarbital and phenytoin). In this article, we present seven children with severe adverse cutaneous reactions caused by barbiturates. The age of the affected children was between 2 and 11 years and they all had a history of taking barbiturates. Their symptoms started 1-3 weeks after the initiation of barbiturates, including a prodrome characterized by 2-3 days of malaise, fever, cough and anorexia, after which the skin and mucosal lesions appeared and worsened. The skin lesions varied from rash to large bullae, plus different forms of mucous membrane involvement. The offending drugs (barbiturates) were stopped immediately and care was largely supportive. As a result of the morbidity and/or mortality associated with EM, SJS and TEN, physicians should keep in mind their differential diagnosis when cutaneous reactions are observed in patients undergoing barbiturate therapy. Furthermore, although TEN and SJS are life-threatening diseases, early detection and appropriate care can lead to a decrease in the incidence of death. The strategies described here seem to be successful and safe because, despite the serious conditions, our patients responded well. All survived.

  8. An Interesting Case of Barbiturate Automatism and Review of Literature

    Directory of Open Access Journals (Sweden)

    Sankalp Gokhale


    Full Text Available A 48 year old man with a diagnosis of HIV infection since 1993, on highly active anti-retro viral therapy (HAART with stable CD4 count and undetectable viral load for years and seizure disorder presented with recurrent drowsiness. His seizures were well controlled on phenobarbitone for years. Repeated laboratory evaluation demonstrated toxic levels of phenobarbitone in his blood. A thorough clinical, psychiatric, laboratory and imaging evaluation did not reveal any obvious etiology for the recurrent barbiturate intoxication in this man. Our findings suggest the possible diagnosis of barbiturate drug automatism in this patient. Though drug automatism is a controversial entity, it merits continued attention. There are recent reports of similar phenomenon with newer sedative agents such as Zolpidem. It is important to be aware of this phenomenon as a possible explanation for recurrent intoxication with barbiturates without a clear etiology for drug overdose.

  9. Comparative Actions of Barbiturates Studied by Pollen Grain Germination. (United States)

    Kordan, Herbert A.; Mumford, Pauline M.


    Describes a simple experimental system whereby the comparative actions of long, medium, and short-acting barbiturates can be demonstrated in a relatively short period of time under optical microscopy using pollen grains as the biological test or assay system. (Author/HM)

  10. Abnormal temperature control after intoxication with short-acting barbiturates. (United States)

    de Villota, E D; Mosquera, J M; Shubin, H; Weil, M H


    Changes in rectal and toe temperatures were measured in 16 patients who had been intoxicated with short-acting barbiturates. The lowest temperatures observed in the group of 16 patients averaged 35.5 +/- 2.0 degrees C. In 11 patients, the interval between intoxication and admission was documented. There was a significant correlation (r = 0.83) between the time of estimated intoxication and hypothermia. Patients who were admitted soon after the ingestion of the barbiturates had the lowest rectal temperatures. These observations indicate that hypothermia is a usual clinical sign in the initial period after intoxication with a short-acting barbiturate. Except for 2 patients, rectal temperature exceeded 38 degrees C during the interval of recovery with the maximum rectal temperature averaging 39.0 +/- 0.8 degrees C. Hyperthermia was not related to infection of the airways, lungs, urinary tract, or bloodstream. In 11 patients, pathogenic organisms were recovered from the airway and/or urine, but there was no difference in the highest rectal temperature in these patients (39.0 +/- 0.9 degrees C) when compared with 5 patients from whom no pathogenic organisms were recovered (39.2 +/- 0.7 degrees C). Accordingly, there was no evidence that hyperthermia was due to infection. The skin temperatures of the ventrum of the first toe were not typically decreased during hypothermia. To the contrary, increases in skin temperatures were often observed during hypothermia. These observations provide evidence of altered thermoregulation with increased surface heat loss accounting for the hypothermia in the early course and heat conservation with hyperthermia during the later course of intoxication by short-acting barbiturates.

  11. Application of thermoresponsive HPLC to forensic toxicology: determination of barbiturates in human urine


    Kanno, Sanae; Watanabe, Kanako; Hirano, Seishiro; Yamagishi, Itaru; Gonmori, Kunio; Minakata, Kayoko; Suzuki, Osamu


    A high-performance liquid chromatography (HPLC) method has been developed for the assays of five barbiturates in human urine using a new thermoresponsive polymer separation column, which is composed of N-isopropylacrylamide polymer. According to elevating the column temperature from 10 ℃ to 50 ℃, five barbiturates, such as metharbital, primidone, phenobarbital, mephobarbital and pentobarbital, became well separated by this method. Five barbiturates showed good linearity in the range of 0.2-10...

  12. Direct radioimmunoassay for the detection of barbiturates in blood and urine

    International Nuclear Information System (INIS)

    Mason, P.A.; Law, B.; Pocock, K.; Moffat, A.C.


    A radioimmunoassay has been developed for the detection of barbiturates in blood and urine without any pre-treatment of the sample. It is based on a radioiodinated derivative of 4-hydroxyphenobarbitone which allows use of relatively simple gamma-counting procedures. The assay can detect therapeutic levels of barbiturates in very small amounts (50 μl) of blood and urine samples. It is cheap, rapid, simple to perform and is broadly specific for the barbiturate class of drugs to the exclusion of related drugs. The assay is, therefore, very well suited to the task of screening large numbers of samples for the presence of barbiturates. (author)

  13. [The identification of barbituric acid derivatives in the old blood stains on textiles]. (United States)

    Kirichek, A V; Shabalina, A E; Rassinskaya, L A

    Thus article was designed to report a few cases of the identification of barbituric acid derivatives in the old blood stains on the clothes and other textiles. The data presented give evidence that barbiturates are capable of persisting in dry blood stains during rather a long period. The authors emphasize the necessity of mandatory control investigations to avoid obtaining the false positive results.

  14. The Physicochemical and Pharmacokinetic Relationships of Barbiturates - From the Past to the Future. (United States)

    Ernst, Britton J; Clark, Gerald F; Grundmann, Oliver


    The pharmacokinetics of different barbiturates have been studied extensively and the relationship of their duration of action to their clinical use has been known for decades. While these particular compounds have largely been displaced by agents with better therapeutic indices, barbiturate use remains relatively common and important in both inpatient and outpatient settings. Their mechanism of action is to bind to inhibitory GABAA receptors in the CNS causing and potentiating the opening of neuronal chloride ion channels thus having a sedative and CNS depressant effect. All psychotropic barbiturates feature di-substitution at the C5 position of the barbituric acid prototype. This is also the primary factor by which physiologically active barbiturates differ from one another and a major mediator of lipophilicity and duration of action. However, in this review, inconsistencies in certain commonly held notions about the structure-activity relationship of barbiturates were found. Commonly accepted chemistry for the structure-activity relationship of barbiturates holds that substitution of larger alkyl groups, alicyclic, and aromatic groups, as well as branching and unsaturation, lead in general to more lipophilic compounds with a shorter biological half-life. This rationale may have limitations in the case of barbiturates as proposed in this review. There is poor correlation between nine clinically used barbiturates' octanol:water partition coefficients (log(P) values) and their respective half-lives. However, a strong correlation between pKa values and half-life was found. The current clinical relevance of these findings is discussed as well as their pertinence to future design and use of barbiturates.

  15. Survey of Opioid and Barbiturate Prescriptions in Patients Attending a Tertiary Care Headache Center. (United States)

    Minen, Mia T; Lindberg, Kate; Wells, Rebecca E; Suzuki, Joji; Grudzen, Corita; Balcer, Laura; Loder, Elizabeth


    To educate physicians about appropriate acute migraine treatment guidelines by determining (1) where headache patients were first prescribed opioids and barbiturates, and (2) the characteristics of the patient population who had been prescribed opioids and barbiturates. Several specialty societies issued recommendations that caution against the indiscriminate use of opioids or barbiturate containing medications for the treatment of migraine. These medications are still being prescribed in various medical settings and could put headache specialists in a difficult position when patients request these agents. Patients presenting to a headache center comprised of eight physicians were asked to complete a survey that assessed headache types, comorbid conditions, and whether they had ever been prescribed opioids or barbiturates. If they responded affirmatively to the latter question, they were asked about the prescribing doctor, medication effectiveness, and whether they were currently on the medication. Data collection took place over a one month period. Two hundred forty-four patients were given the survey and 218 of these patients completed it. The predominant diagnosis was migraine (83.9%). More than half of the patients reported having been prescribed an opioid (54.8%) or a barbiturate (56.7%). About one fifth were on opioids (19.4%) or barbiturates (20.7%) at the time of completing the survey. Most patients reported being on opioids for more than 2 years (24.6%) or less than one week (32.1%). The reasons most frequently cited for stopping opioids were that the medications did not help (30.9%) or that they saw a new doctor who would not prescribe them (29.4%). Among patients who had previously been on barbiturates, 32.2% had been on these for over 2 years. Most patients (61.8%) stopped barbiturates because they did not find the medication helpful, while 17.6% said they saw a new doctor who would not prescribe them. The physician specialty most frequently cited as

  16. Synthesis and Antiangiogenic Properties of Tetrafluorophthalimido and Tetrafluorobenzamido Barbituric Acids. (United States)

    Ambrożak, Agnieszka; Steinebach, Christian; Gardner, Erin R; Beedie, Shaunna L; Schnakenburg, Gregor; Figg, William D; Gütschow, Michael


    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. Tetrafluorination of the phthalimide moiety in tetrafluorophthalimidobarbituric acids was essential, as all of the nonfluorinated counterparts lost anti-angiogenic activity. An opening of the five-membered ring and the accompanying increased conformational freedom, in case of the corresponding tetrafluorobenzamidobarbituric acids, was well tolerated. Their activity was retained, although their molecular structures differ in torsional flexibility and possible hydrogen-bond networking, as revealed by comparative X-ray crystallographic analyses. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Reversible photocapture of a [2]rotaxane harnessing a barbiturate template. (United States)

    Tron, Arnaud; Thornton, Peter J; Lincheneau, Christophe; Desvergne, Jean-Pierre; Spencer, Neil; Tucker, James H R; McClenaghan, Nathan D


    Photoirradiation of a hydrogen-bonded molecular complex comprising acyclic components, namely, a stoppered thread (1) with a central barbiturate motif and an optimized doubly anthracene-terminated acyclic Hamilton-like receptor (2b), leads to an interlocked architecture, which was isolated and fully characterized. The sole isolated interlocked photoproduct (Φ = 0.06) is a [2]rotaxane, with the dimerized anthracenes assuming a head-to-tail geometry, as evidenced by NMR spectroscopy and consistent with molecular modeling (PM6). A different behavior was observed on irradiating homologous molecular complexes 1⊂2a, 1⊂2b, and 1⊂2c, where the spacers of 2a, 2b, and 2c incorporated 3, 6, and 9 methylene units, respectively. While no evidence of interlocked structure formation was observed following irradiation of 1⊂2a, a kinetically labile rotaxane was obtained on irradiating the complex 1⊂2c, and ring slippage was revealed. A more stable [2]rotaxane was formed on irradiating 1⊂2b, whose capture is found to be fully reversible upon heating, thereby resetting the system, with some fatigue (38%) after four irradiation–thermal reversion cycles.

  18. Capacities of Follow-up of the Severity of Acute Barbiturate Intoxications and their Prediction

    Directory of Open Access Journals (Sweden)

    I. I. Vorobyeva


    Full Text Available Seventy-eight patients with moderate, severe, and fatal (n = 12 acute intoxication with barbiturates, as evidenced by the measurements of their blood concentrations were examined. Cardiointervalography was made during follow-up ECG in all the patients in order to determine the tension index (TI, a cumulative measure of the tone of the autonomic nervous system. Comparison of clinical, laboratory, and cardiointervalographic data showed that sympathicotonia (TI, 90—160 conventional units was predominant in moderate intoxication with barbiturates (their concentration was 16.14±3.2 ^g/ml, there was hypersympathicotonia (TI, more than 160 conventional units in severe intoxication (the concentration of barbiturates, 30.56±7.6 ^g/ml; the increased tone of the parasympathetic portion of the autonomic nervous system — vagotonia (TI, less than 30 conventional units in fatal intoxication (the concentration of barbiturates, 37.3±6.6 ^g/ml. Moreover, TI decreased with the age of patients and increased with combined intoxication with barbiturates and alcohol (its blood concentration was more than 1 g/l.

  19. Prophylactic barbiturate use for the prevention of morbidity and mortality following perinatal asphyxia. (United States)

    Young, Leslie; Berg, Marie; Soll, Roger


    Seizures are common following perinatal asphyxia and may exacerbate secondary neuronal injury. Barbiturate therapy has been used for infants with perinatal asphyxia in order to prevent seizures. However, barbiturate therapy may adversely affect neurodevelopment leading to concern regarding aggressive use in neonates. To determine the effect of administering prophylactic barbiturate therapy on death or neurodevelopmental disability in term and late preterm infants following perinatal asphyxia. We used the standard search strategy of the Cochrane Neonatal Review group to search the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 11), MEDLINE via PubMed (1966 to 30 November 2015), EMBASE (1980 to 30 November 2015), and CINAHL (1982 to 30 November 2015). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials (RCT) and quasi-RCTs. We included all RCTs or quasi-RCTs of prophylactic barbiturate therapy in term and late preterm infants without clinical or electroencephalographic evidence of seizures compared to controls following perinatal asphyxia. Three review authors independently selected, assessed the quality of, and extracted data from the included studies. We assessed methodologic quality and validity of studies without consideration of the results. The review authors independently extracted data and performed meta-analyses using risk ratios (RR) and risk differences (RD) for dichotomous data and mean difference for continuous data with 95% confidence intervals (CI). For significant results, we calculated the number needed to treat for an additional beneficial outcome (NNTB) or for an additional harmful outcome (NNTH). In this updated review, we identified nine RCTs of any barbiturate therapy in term and late preterm infants aged less than three days old with perinatal asphyxia without evidence of seizures. Eight of these studies compared prophylactic

  20. Structure-activity relationships of convulsant and anticonvulsant barbiturates: a computer-graphic-based pattern-recognition analysis. (United States)

    Andrews, P R; Mark, L C; Winkler, D A; Jones, G P


    A computer-graphic-based pattern-recognition study of two series of 5-ethyl-5-substituted barbiturates has been undertaken in an attempt to find a correlation between molecular conformation and convulsant and anticonvulsant activity. Studies of a first (trial) set of barbiturates related to pentobarbital revealed a region of space in which at least one low-energy conformation of the hydrocarbon side chain of each of the anticonvulsant barbiturates resides. Another region was occupied by a low-energy conformation of each of the convulsant barbiturates. These regions of space are, thus, possible pharmacophores for convulsant and anticonvulsant activity. Analysis of a second (test) set of barbiturates related to phenobarbital has shown that the activities and structures of these molecules are consistent with the above model. These pharmacophores thus provide a basis for the design of rigid, new analogues with potent convulsant or anticonvulsant activities.

  1. Recognition of anesthetic barbiturates by a protein binding site: a high resolution structural analysis.

    Directory of Open Access Journals (Sweden)

    Simon Oakley

    Full Text Available Barbiturates potentiate GABA actions at the GABA(A receptor and act as central nervous system depressants that can induce effects ranging from sedation to general anesthesia. No structural information has been available about how barbiturates are recognized by their protein targets. For this reason, we tested whether these drugs were able to bind specifically to horse spleen apoferritin, a model protein that has previously been shown to bind many anesthetic agents with affinities that are closely correlated with anesthetic potency. Thiopental, pentobarbital, and phenobarbital were all found to bind to apoferritin with affinities ranging from 10-500 µM, approximately matching the concentrations required to produce anesthetic and GABAergic responses. X-ray crystal structures were determined for the complexes of apoferritin with thiopental and pentobarbital at resolutions of 1.9 and 2.0 Å, respectively. These structures reveal that the barbiturates bind to a cavity in the apoferritin shell that also binds haloalkanes, halogenated ethers, and propofol. Unlike these other general anesthetics, however, which rely entirely upon van der Waals interactions and the hydrophobic effect for recognition, the barbiturates are recognized in the apoferritin site using a mixture of both polar and nonpolar interactions. These results suggest that any protein binding site that is able to recognize and respond to the chemically and structurally diverse set of compounds used as general anesthetics is likely to include a versatile mixture of both polar and hydrophobic elements.

  2. Synthesis and steriostructure of 5-(5-R-2- furfur lidene)- barbituric acid

    International Nuclear Information System (INIS)

    Abdel-Wahab, A.


    Heterocyclic compounds 5-(5-R-2-furfur lidene)- barbituric acid were obtained and their physical and chemical properties were studied. Their structures were identified by spectroscopic methods. This study proved by 1 H-NMR Spectroscopy data that these compounds exist in S-cis form. (author)

  3. Complementary hydrogen bonding of a carboxylato-barbiturate with urea and acetamide: Experimental and theoretical approach

    Czech Academy of Sciences Publication Activity Database

    Hasan, Md. A.; Seshaditya, A.; Záliš, Stanislav; Mishra, L.


    Roč. 83, č. 1 (2011), s. 532-539 ISSN 1386-1425 Institutional research plan: CEZ:AV0Z40400503 Keywords : barbiturate derivative * binding study * 1H-NMR titration Subject RIV: CG - Electrochemistry Impact factor: 2.098, year: 2011

  4. Barbiturate ingestion in three adult captive tigers (Panthera tigris) and concomitant fatal botulism of one. (United States)

    Williams, J H; Bester, L; Venter, L; Pretorius, D; Greyling, F


    Zoo animals, including tigers, have been reported to suffer from barbiturate intoxication, with pentabarbitone being most commonly recorded. Clinical signs range from mild ataxia to general anaesthesia with recovery over hours to days with several factors affecting hepatic barbiturate metabolism and tissue partitioning. Botulism is an often fatal intoxication in man, animals, birds and certain fish. The occurrence in carnivores is uncommon to rare, with only 2 reports found of botulism in felids. This report relates to 3 adult captive cohabiting tigers that simultaneously developed signs of abdominal discomfort, progressive ataxia, recumbency and comatose sleep resembling stage 2 anaesthesia, alternating with periods of distracted wakefulness and ataxic movements. These signs occurred 4 days after being fed the carcass of a horse that had ostensibly died of colic and not been euthanased. The male tiger that was the dominant animal in the feeding hierarchy was worst affected and had to be given intravenous fluids. The female that was lowest in hierarchy was unaffected. After 48-72 hours of treatment at the Onderstepoort Veterinary Academic Hospital the females could eat and made an uneventful recovery. The male tiger showed partial recovery but died during the night a few hours after drinking water on his return to the owner. Necropsy revealed severe oesophageal dilation and impaction with decaying grass; some of this material and water were present in the pharynx and trachea, and had been aspirated causing acute widespread bronchopneumonia. Colon content tested negative for common pesticides but, together with liver, tested positive for barbiturate. Serum taken on the day of admission had tested negative for barbiturate and the residual serum from the 3 animals later tested negative for botulinum toxin. Colon and oesophageal content from the male at necropsy were positive for Clostridium botulinum toxin type C by the mouse bioassay neutralisation test, confirming

  5. Allyl m-Trifluoromethyldiazirine Mephobarbital: An Unusually Potent Enantioselective and Photoreactive Barbiturate General Anesthetic

    Energy Technology Data Exchange (ETDEWEB)

    Savechenkov, Pavel Y.; Zhang, Xi; Chiara, David C.; Stewart, Deirdre S.; Ge, Rile; Zhou, Xiaojuan; Raines, Douglas E.; Cohen, Jonathan B.; Forman, Stuart A.; Miller, Keith W.; Bruzik, Karol S. (Harvard-Med); (Mass. Gen. Hosp.); (UIC)


    We synthesized 5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (14), a trifluoromethyldiazirine-containing derivative of general anesthetic mephobarbital, separated the racemic mixture into enantiomers by chiral chromatography, and determined the configuration of the (+)-enantiomer as S by X-ray crystallography. Additionally, we obtained the {sup 3}H-labeled ligand with high specific radioactivity. R-(-)-14 is an order of magnitude more potent than the most potent clinically used barbiturate, thiopental, and its general anesthetic EC{sub 50} approaches those for propofol and etomidate, whereas S-(+)-14 is 10-fold less potent. Furthermore, at concentrations close to its anesthetic potency, R-(-)-14 both potentiated GABA-induced currents and increased the affinity for the agonist muscimol in human {alpha}1{beta}2/3{gamma}2L GABA{sub A} receptors. Finally, R-(-)-14 was found to be an exceptionally efficient photolabeling reagent, incorporating into both {alpha}1 and {beta}3 subunits of human {alpha}1{beta}3 GABAA receptors. These results indicate R-(-)-14 is a functional general anesthetic that is well-suited for identifying barbiturate binding sites on Cys-loop receptors.

  6. A Greener, Efficient Approach to Michael Addition of Barbituric Acid to Nitroalkene in Aqueous Diethylamine Medium

    Directory of Open Access Journals (Sweden)

    Hany J. Al-Najjar


    Full Text Available An efficient method for the synthesis of a variety of pyrimidine derivatives 3a–t by reaction of barbituric acids 1a,b as Michael donor with nitroalkenes 2a–k as Michael acceptor using an aqueous medium and diethylamine is described. This 1,4-addition strategy offers several advantages, such as using an economic and environmentally benign reaction media, high yields, versatility, and shorter reaction times. The synthesized compounds were identified by 1H-NMR, 13C-NMR, CHN, IR, and MS. The structure of compound 3a was further confirmed by single crystal X-ray structure determination.

  7. Determination of the rate constants of the reactions CO/sub 2/+OH/sup -/ -> HCO/sub 3//sup -/ and barbituric acid -> barbiturate anion -> H/sup -/ using the pulse radiolyse technique

    Energy Technology Data Exchange (ETDEWEB)

    Schuchmann, M.N.; von Sonntag, C.


    The kinetics of the reactions of CO/sub 2/ + OH /sup -/-> HCO/sub 3//sup -/ (i) and barbituric acid -> barbiturate anion + H/sup +/ (ii) have been remeasured using as a new approach the pulse radiolysis technique with optical and conductivity detection. The rate constants obtained in the present study, ksub(j) (21/sup 0/C) = 6900 +- 700 M/sup -1/ s/sup -1/ and ksub(II) (19/sup 0/C) = 22 +- 2 s/sup -1/ agree within experimental errors with values obtained earlier by other methods.

  8. Hyperalgesic effect induced by barbiturates, midazolam and ethanol: pharmacological evidence for GABA-A receptor involvement

    Directory of Open Access Journals (Sweden)

    M.A.K.F. Tatsuo


    Full Text Available The involvement of GABA-A receptors in the control of nociception was studied using the tail-flick test in rats. Non-hypnotic doses of the barbiturates phenobarbital (5-50 mg/kg, pentobarbital (17-33 mg/kg, and thiopental (7.5-30 mg/kg, of the benzodiazepine midazolam (10 mg/kg or of ethanol (0.4-1.6 g/kg administered by the systemic route reduced the latency for the tail-flick response, thus inducing a 'hyperalgesic' state in the animals. In contrast, non-convulsant doses of the GABA-A antagonist picrotoxin (0.12-1.0 mg/kg administered systemically induced an increase in the latency for the tail-flick response, therefore characterizing an 'antinociceptive' state. Previous picrotoxin (0.12 mg/kg treatment abolished the hyperalgesic state induced by effective doses of the barbiturates, midazolam or ethanol. Since phenobarbital, midazolam and ethanol reproduced the described hyperalgesic effect of GABA-A-specific agonists (muscimol, THIP, which is specifically antagonized by the GABA-A antagonist picrotoxin, our results suggest that GABA-A receptors are tonically involved in the modulation of nociception in the rat central nervous system

  9. Barbiturate end-capped non-fullerene acceptors for organic solar cells: tuning acceptor energetics to suppress geminate recombination losses. (United States)

    Tan, Ching-Hong; Gorman, Jeffrey; Wadsworth, Andrew; Holliday, Sarah; Subramaniyan, Selvam; Jenekhe, Samson A; Baran, Derya; McCulloch, Iain; Durrant, James R


    We report the synthesis of two barbiturate end-capped non-fullerene acceptors and demonstrate their efficient function in high voltage output organic solar cells. The acceptor with the lower LUMO level is shown to exhibit suppressed geminate recombination losses, resulting in enhanced photocurrent generation and higher overall device efficiency.

  10. Simultaneous effect of organic modifier and physicochemical parameters of barbiturates on their retention on a narrow-bore PGC column

    Czech Academy of Sciences Publication Activity Database

    Forgács, E.; Cserháti, T.; Mikšík, Ivan; Eckhardt, Adam; Deyl, Zdeněk


    Roč. 800, č. 1-2 (2004), s. 259-262 ISSN 1570-0232 Grant - others:CZ - HU(CZ) Cooperation programme Institutional research plan: CEZ:AV0Z5011922 Keywords : barbiturates * porous graphitized carbon Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 2.176, year: 2004

  11. Barbiturate End-Capped Non-Fullerene Acceptors for Organic Solar Cells: Tuning Acceptor Energetics to Suppress Geminate Recombination Losses

    KAUST Repository

    Tan, Ching-Hong


    We report the synthesis of two barbiturate end-capped non-fullerene acceptors and demonstrate their efficient function in high voltage output organic solar cells. The acceptor with the lower LUMO level is shown to exhibit suppressed geminate recombination losses, resulting in enhanced photocurrent generation and higher overall device efficiency.

  12. Hydrogen bond donor–acceptor–donor organocatalysis for conjugate addition of benzylidene barbiturates via complementary DAD– ADA hydrogen bonding

    NARCIS (Netherlands)

    Leung, King-Chi; Cui, Jian-Fang; Hui, Tsz-Wai; Zhou, Zhong-Yuan; Wong, Man-Kin


    A new class of hydrogen bond donor-acceptor-donor (HB-DAD) organocatalysts has been developed for conjugate addition of benzylidene barbiturates. HB-DAD organocatalyst 1a (featuring para-chloro-pyrimidine as the hydrogen bond acceptor (HBA), N-H as the hydrogen bond donor (HBD) and a trifluoroacetyl

  13. Estimation of very low concentrations of Ruthenium by spectrophotometric method using barbituric acid as complexing agent

    International Nuclear Information System (INIS)

    Ramakrishna Reddy, S.; Srinivasan, R.; Mallika, C.; Kamachi Mudali, U.; Natarajan, R.


    Spectrophotometric method employing numerous chromogenic reagents like thiourea, 1,10-phenanthroline, thiocyanate and tropolone is reported in the literature for the estimation of very low concentrations of Ru. A sensitive spectrophotometric method has been developed for the determination of ruthenium in the concentration range 1.5 to 6.5 ppm in the present work. This method is based on the reaction of ruthenium with barbituric acid to produce ruthenium(ll)tris-violurate, (Ru(H 2 Va) 3 ) -1 complex which gives a stable deep-red coloured solution. The maximum absorption of the complex is at 491 nm due to the inverted t 2g → Π(L-L ligand) electron - transfer transition. The molar absorptivity of the coloured species is 9,851 dm 3 mol -1 cm -1

  14. Barbiturate ingestion in three adult captive tigers (Panthera tigris and concomitant fatal botulism of one : clinical communication

    Directory of Open Access Journals (Sweden)

    J. H. Williams


    Full Text Available Zoo animals, including tigers, have been reported to suffer from barbiturate intoxication, with pentabarbitone being most commonly recorded. Clinical signs range from mild ataxia to general anaesthesia with recovery over hours to days with several factors affecting hepatic barbiturate metabolism and tissue partitioning. Botulism is an often fatal intoxication in man, animals, birds and certain fish. The occurrence in carnivores is uncommon to rare, with only 2 reports found of botulism in felids. This report relates to 3 adult captive cohabiting tigers that simultaneously developed signs of abdominal discomfort, progressive ataxia, recumbency and comatose sleep resembling stage 2 anaesthesia, alternating with periods of distracted wakefulness and ataxic movements. These signs occurred 4 days after being fed the carcass of a horse that had ostensibly died of colic and not been euthanased. The male tiger that was the dominant animal in the feeding hierarchy was worst affected and had to be given intravenous fluids. The female that was lowest in hierarchy was unaffected. After 48-72 hours of treatment at the Onderstepoort Veterinary Academic Hospital the females could eat and made an uneventful recovery. The male tiger showed partial recovery but died during the night a few hours after drinking water on his return to the owner. Necropsy revealed severe oesophageal dilation and impaction with decaying grass; some of this material and water were present in the pharynx and trachea, and had been aspirated causing acute widespread bronchopneumonia. Colon content tested negative for common pesticides but, together with liver, tested positive for barbiturate. Serum taken on the day of admission had tested negative for barbiturate and the residual serum from the 3 animals later tested negative for botulinum toxin. Colon and oesophageal content from the male at necropsy were positive for Clostridium botulinum toxin type C by the mouse bioassay

  15. Temperature- and moisture-dependent phase changes in crystal forms of barbituric acid

    Energy Technology Data Exchange (ETDEWEB)

    Zencirci, Neslihan; Gstrein, Elisabeth; Langes, Christoph [Institute of Pharmacy, Faculty of Chemistry and Pharmacy, University of Innsbruck, Innrain 52, 6020 Innsbruck (Austria); Griesser, Ulrich J. [Institute of Pharmacy, Faculty of Chemistry and Pharmacy, University of Innsbruck, Innrain 52, 6020 Innsbruck (Austria)], E-mail:


    The dihydrate of barbituric acid (BAc) and its dehydration product, form II were investigated by means of moisture sorption analysis, hot-stage microscopy, differential scanning calorimetry, thermogravimetry, solution calorimetry, IR- and Raman-spectroscopy as well as powder X-ray diffraction. The dihydrate desolvates already at and below 50% relative humidity (RH) at 25 deg. C whereas form II is stable up to 80% RH, where it transforms back to the dihydrate. The thermal dehydration of barbituric acid dihydrate (BAc-H2) is a single step, nucleation controlled process. The peritectic reaction of the hydrate was measured at 77 deg. C and a transformation enthalpy of {delta}{sub trs}H{sub H2-II} = 17.3 kJ mol{sup -1} was calculated for the interconversion between the hydrate and form II. An almost identical value of 17.0 kJ mol{sup -1} was obtained from solution calorimetry in water as solvent ({delta}{sub sol}H{sub H2} = 41.5, {delta}{sub sol}H{sub II} = 24.5 kJ mol{sup -1}). Additionally a high-temperature form (HT-form) of BAc, which is enantiotropically related to form II and unstable at ambient conditions has been characterized. Furthermore, we observed that grinding of BAc with potassium bromide (KBr) induces a tautomeric change. Therefore, IR-spectra recorded with KBr-discs usually display a mixture of tautomers, whereas the IR-spectra of the pure trioxo-form of BAc are obtained if alternative preparation techniques are used.

  16. Nucleobase-Based Barbiturates: Their Protective Effect against DNA Damage Induced by Bleomycin-Iron, Antioxidant, and Lymphocyte Transformation Assay

    Directory of Open Access Journals (Sweden)

    Bhaveshkumar D. Dhorajiya


    Full Text Available A number of nucleobase-based barbiturates have been synthesized by combination of nucleic acid bases and heterocyclic amines and barbituric acid derivatives through green and efficient multicomponent route and one pot reaction. This approach was accomplished efficiently using aqueous medium to give the corresponding products in high yield. The newly synthesized compounds were characterized by spectral analysis (FT-IR, 1H NMR, 13C NMR, HMBC, and UV spectroscopy and elemental analysis. Representative of all synthesized compounds was tested and evaluated for antioxidant, bleomycin-dependent DNA damage, and Lymphocyte Transformation studies. Compounds TBC > TBA > TBG showed highest lymphocyte transformation assay, TBC > TBA > BG showed inhibitory antioxidant activity using ABTS methods, and TBC > BPA > BAMT > TBA > 1, 3-TBA manifested the best protective effect against DNA damage induced by bleomycin.

  17. Behaviour of Some Activated Nitriles Toward Barbituric Acid, Thiobarbituric Acid and 3-Methyl-1-Phenylpyrazol-5-one

    Directory of Open Access Journals (Sweden)

    M. M. Habashy


    Full Text Available The effect of some active methylene containing heterocyclic compounds, namely barbituric acid, thiobarbituric acid and 3-methyl-1-phenylpyrazol-5-one on a-cyano-3,4,5-trimethoxycinnamonitrile and ethyl a-cyano-3,4,5-trimethoxycinnamate (1a,b was investigated. The structure of the new products was substantiated by their IR,1H-NMR and mass spectra.

  18. Piracetam and TRH analogues antagonise inhibition by barbiturates, diazepam, melatonin and galanin of human erythrocyte D-glucose transport


    Naftalin, Richard J; Cunningham, Philip; Afzal-Ahmed, Iram


    Nootropic drugs increase glucose uptake into anaesthetised brain and into Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a chemical structure similar to nootropics increases cerebellar uptake of glucose in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2-oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH antagonise the inhibition of glucose transport by barbiturates, diazepam, melatonin and endogenous neuropeptide...

  19. Inhibition of matrix metalloproteinase-9 by a barbiturate-nitrate hybrid ameliorates dextran sulphate sodium-induced colitis: effect on inflammation-related genes. (United States)

    O'Sullivan, Shane; Wang, Jun; Pigott, Maria T; Docherty, Neil; Boyle, Noreen; Lis, Samuel Kana; Gilmer, John F; Medina, Carlos


    Matrix metalloproteinase-9 (MMP-9) is up-regulated in ulcerative colitis and implicated in the pathology of the disease. In this study, we have examined the effects of a barbiturate-based MMP inhibitor incorporating a nitric oxide donor/mimetic group (dinitrate-barbiturate) on the intestinal injury induced by dextran sulphate sodium (DSS). In vivo experiments were carried out using male Wistar rats given 5% DSS ad libitum in drinking water. The dinitrate-barbiturate, non-nitrate equivalent, nitrate side chains alone or vehicle were administered rectally, twice daily. MMP-9 release was measured by gelatin zymography, and analysis of gene expression was carried out using RT-qPCR. TaqMan low density arrays were used to evaluate the expression of 91 inflammatory genes in the rat colon. The dinitrate-barbiturate inhibited the induction and activity of MMP-9 during DSS colitis in the rat. This occurred in association with significant reductions in the colitic response to DSS as assessed by an established clinical disease activity index and a pathological colitis grade score. The compound modified expression rates of numerous inflammation-related genes in the colon. This study demonstrated the efficacy of the dinitrate-barbiturate in DSS-induced colitis. Therefore, barbiturate-nitrate hybrids may be developed as a promising anti-inflammatory approach to the treatment of inflammatory bowel disease. © 2017 The British Pharmacological Society.

  20. On the Action of General Anesthetics on Cellular Function: Barbiturate Alters the Exocytosis of Catecholamines in a Model Cell System. (United States)

    Ye, Daixin; Ewing, Andrew


    General anesthetics are essential in many areas, however, the cellular mechanisms of anesthetic-induced amnesia and unconsciousness are incompletely understood. Exocytosis is the main mechanism of signal transduction and neuronal communication through the release of chemical transmitters from vesicles to the extracellular environment. Here, we use disk electrodes placed on top of PC12 cells to show that treatment with barbiturate induces fewer molecules released during exocytosis and changes the event dynamics perhaps by inducing a less stable fusion pore that is prone to close faster during partial exocytosis. Larger events are essentially abolished. However, use of intracellular vesicle impact electrochemical cytometry using a nano-tip electrode inserted into a cell shows that the distribution of vesicle transmitter content does not change after barbiturate treatment. This indicates that barbiturate selectively alters the pore size of larger events or perhaps differentially between types of vesicles. Alteration of exocytosis in this manner could be linked to the effects of general anesthetics on memory loss. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Evolution of Cerebral Atrophy in a Patient with Super Refractory Status Epilepticus Treated with Barbiturate Coma

    Directory of Open Access Journals (Sweden)

    Christopher R. Newey


    Full Text Available Introduction. Status epilepticus is associated with neuronal breakdown. Radiological sequelae of status epilepticus include diffusion weighted abnormalities and T2/FLAIR cortical hyperintensities corresponding to the epileptogenic cortex. However, progressive generalized cerebral atrophy from status epilepticus is underrecognized and may be related to neuronal death. We present here a case of diffuse cerebral atrophy that developed during the course of super refractory status epilepticus management despite prolonged barbiturate coma. Methods. Case report and review of the literature. Case. A 19-year-old male with a prior history of epilepsy presented with focal clonic seizures. His seizures were refractory to multiple anticonvulsants and eventually required pentobarbital coma for 62 days and midazolam coma for 33 days. Serial brain magnetic resonance imaging (MRI showed development of cerebral atrophy at 31 days after admission to our facility and progression of the atrophy at 136 days after admission. Conclusion. This case highlights the development and progression of generalized cerebral atrophy in super refractory status epilepticus. The cerebral atrophy was noticeable at 31 days after admission at our facility which emphasizes the urgency of definitive treatment in patients who present with super refractory status epilepticus. Further research into direct effects of therapeutic coma is warranted.

  2. Trisubstituted barbiturates and thiobarbiturates: Synthesis and biological evaluation as xanthine oxidase inhibitors, antioxidants, antibacterial and anti-proliferative agents. (United States)

    Figueiredo, Joana; Serrano, João L; Cavalheiro, Eunice; Keurulainen, Leena; Yli-Kauhaluoma, Jari; Moreira, Vânia M; Ferreira, Susana; Domingues, Fernanda C; Silvestre, Samuel; Almeida, Paulo


    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 50 values of 24.3 and 27.9 μM, respectively), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (IC 50 values of 18.8 and 23.8 μM, respectively). In addition, 5-[1-(2-phenylhydrazinyl)ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6d) also revealed DPPH radical scavenger effect, with an IC 50 value of 20.4 μM. Moreover, relevant cytotoxicity against MCF-7 cells (IC 50  = 13.3 μM) was observed with 5-[[(2-chloro-4-nitrophenyl)amino]methylene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (7d). Finally, different 5-hydrazinylethylidenepyrimidines revealed antibacterial activity against Acinetobacter baumannii (MIC values between 12.5 and 25.0 μM) which paves the way for developing new treatments for infections caused by this Gram-negative coccobacillus bacterium, known to be an opportunistic pathogen in humans with high relevance in multidrug-resistant nosocomial infections. The most promising bioactive barbiturates were studied in silico with emphasis on compliance with the Lipinski's rule of five as well as several pharmacokinetics and toxicity parameters. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  3. Synthesis and Evaluation of Changes Induced by Solvent and Substituent in Electronic Absorption Spectra of New Azo Disperse Dyes Containig Barbiturate Ring

    Directory of Open Access Journals (Sweden)

    Hooshang Hamidian


    Full Text Available Six azo disperse dyes were prepared by diazotizing 4-amino hippuric acid and coupled with barbituric acid and 2-thiobarbituric acid. Then, the products were reacted with aromatic aldehyde, sodium acetate, and acetic anhydride, and oxazolone derivatives were formed. Characterization of the dyes was carried out by using UV-Vis, FT-IR, 1H NMR and 13C NMR, and mass spectroscopic techniques. The solvatochromic behavior of azo disperse dyes was evaluated in various solvents. The effects of substituents of aromatic aldehyde, barbiturate, and thiobarbiturate ring on the color of dyes were investigated.

  4. Reliability of self-reported use of amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates among acutely hospitalized elderly medical patients

    DEFF Research Database (Denmark)

    Glintborg, B.; Olsen, L.; Poulsen, H.


    Undisclosed use of illicit drugs and prescription controlled substances is frequent in some settings. The aim of the present study was to estimate the reliability of self-reported use of amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates among acutely...

  5. The determination of pentobarbital and other barbiturates in blood plasma by gas—liquid chromatography with on-column and pre-column butylation

    NARCIS (Netherlands)

    Hulshoff, A.; Houwen, O.A.G.J. van der; Barends, D.M.; Kostenbauder, H.B.


    Two g.l.c. methods for the determination of pentobarbital and other barbiturates are reported. In the first method the plasma samples are extracted with toluene; the toluene layer is back-extracted with a small volume of a tetrabutylammonium hydroxide solution of which an aliquot is injected into

  6. Synthesis, X-Ray Crystal Structures, Biological Evaluation, and Molecular Docking Studies of a Series of Barbiturate Derivatives

    Directory of Open Access Journals (Sweden)

    Assem Barakat


    Full Text Available A series of barbiturates derivatives synthesized and screened for different set of bioassays are described. The molecular structures of compounds 5a, 5d, and 5f were solved by single-crystal X-ray diffraction techniques. The results of bioassay show that compounds 4a, 4b, 4c, 4d, 4e, 4f, and 4g are potent antioxidants in comparison to the tested standards, butylated hydroxytoluene (BHT, and N-acetylcysteine. Compounds 4a–4e (IC50=101.8±0.8–124.4±4.4 μM and 4g (IC50=104.1±1.9 μM were more potent antioxidants than the standard (BHT, IC50=128.8±2.1 μM. The enzyme inhibition potential of these compounds was also evaluated, in vitro, against thymidine phosphorylase, α-glucosidase, and β-glucuronidase enzymes. Compounds 4c, 4h, 4o, 4p, 4q, 5f, and 5m were found to be potent α-glucosidase inhibitors and showed more activity than the standard drug acarbose, whereas compounds 4v, and 5h were found to be potent thymidine phosphorylase inhibitors, more active than the standard drug, 7-deazaxanthine. All barbiturates derivatives (4a–4x, 4z, and 5a–5m were found to be noncytotoxic against human prostate (PC-3, Henrietta Lacks cervical (HeLa and Michigan Cancer Foundation-7 breast (MCF-7 cancer cell lines, and 3T3 normal fibroblast cell line, except 4y which was cytotoxic against all the cell lines.

  7. Antibacterial Barbituric Acid Analogues Inspired from Natural 3-Acyltetramic Acids; Synthesis, Tautomerism and Structure and Physicochemical Property-Antibacterial Activity Relationships

    Directory of Open Access Journals (Sweden)

    Yong-Chul Jeong


    Full Text Available The synthesis, tautomerism and antibacterial activity of novel barbiturates is reported. In particular, 3-acyl and 3-carboxamidobarbiturates exhibited antibacterial activity, against susceptible and some resistant Gram-positive strains of particular interest is that these systems possess amenable molecular weight, rotatable bonds and number of proton-donors/acceptors for drug design as well as less lipophilic character, with physicochemical properties and ionic states that are similar to current antibiotic agents for oral and injectable use. Unfortunately, the reduction of plasma protein affinity by the barbituric core is not sufficient to achieve activity in vivo. Further optimization to reduce plasma protein affinity and/or elevate antibiotic potency is therefore required, but we believe that these systems offer unusual opportunities for antibiotic drug discovery.

  8. Absorption of folic acid and its rate of disappearance from the blood of patients receiving barbiturates in excess in combination with alcohol

    International Nuclear Information System (INIS)

    Gyftaki, H.; Kesse-Elias, M.; Alevizou-Terzaki, V.; Rapidis, P.; Sdougou-Christakopoulou, J.


    It is known that megaloblastic anaemia may occur from the intake of phenobarbital, which apparently responds to folic acid and vitamin B 12 . Its site of action is not known but there is evidence that it may act as a pyrimidine antagonist. It is also known that alcoholics with or without cirrhosis have folate deficiency. Furthermore, although potentiating effects of alcohol and barbiturates exist it is not known how the combination of barbiturates and alcohol acts on folic acid metabolism. In thirty patients receiving barbiturates in excess in combination with alcohol, absorption of folic acid and its rate of disappearance were studied in the blood. Two series of studies were performed. In the first, folic acid (15μg/kg of body weight) was administered orally and the maximum concentration in the blood as well as its disappearance rate were determined. In the second, folinic acid (15 μg/kg of body weight) was administered intramuscularly and the disappearance rate of folic acid was again determined. Blood samples were taken at certain intervals after administration of folic or folinic acid. Estimation of serum folic acid level was obtained by a competitive protein-binding technique developed in our laboratory. The results are discussed and compared with those in normal subjects. (author)

  9. Optical characterization and blu-ray recording properties of metal(II) azo barbituric acid complex films

    Energy Technology Data Exchange (ETDEWEB)

    Li, X.Y. [Shanghai Institute of Optics and Fine Mechanics, Chinese Academy of Sciences, Shanghai 201800 (China)], E-mail:; Wu, Y.Q. [Shanghai Institute of Optics and Fine Mechanics, Chinese Academy of Sciences, Shanghai 201800 (China); Key Lab of Functional Inorganic Material Chemistry (Heilongjiang University), Ministry of Education, Haerbin 150080 (China)], E-mail:; Gu, D.D.; Gan, F.X. [Shanghai Institute of Optics and Fine Mechanics, Chinese Academy of Sciences, Shanghai 201800 (China)


    Smooth thin films of nickel(II), cobalt(II) and zinc(II) complexes with azo barbituric acid were prepared by the spin-coating method. Absorption spectra of the thin films on K9 glass substrates in 300-700 nm wavelength region were measured. Optical constants (complex refractive index N = n + ik) of the thin films prepared on single-crystal silicon substrates in 275-695 nm wavelength region were investigated on rotating analyzer-polarizer type of scanning ellipsometer, and dielectric constant {epsilon} ({epsilon} = {epsilon}{sub 1} + i{epsilon}{sub 2}) as well as absorption coefficient {alpha} of thin films were calculated at 405 nm. In addition, static optical recording properties of the cobalt(II) complex thin film with an Ag reflective layer was carried out using a 406.7 nm blue-violet laser and a high numerical aperture (NA) of 0.90. Clear recording marks with high reflectivity contrast (>60%) at proper laser power and pulse width were obtained, and the size of recording mark was as small as 250 nm. The results indicate that these metal(II) complexes are promising organic recording medium for the blu-ray optical storage system.

  10. Piracetam and TRH analogues antagonise inhibition by barbiturates, diazepam, melatonin and galanin of human erythrocyte D-glucose transport. (United States)

    Naftalin, Richard J; Cunningham, Philip; Afzal-Ahmed, Iram


    1 Nootropic drugs increase glucose uptake into anaesthetised brain and into Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a chemical structure similar to nootropics increases cerebellar uptake of glucose in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2-oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH antagonise the inhibition of glucose transport by barbiturates, diazepam, melatonin and endogenous neuropeptide galanin in human erythrocytes in vitro. 2 The potencies of nootropic drugs in opposing scopolamine-induced memory loss correlate with their potencies in antagonising pentobarbital inhibition of erythrocyte glucose transport in vitro (Paniracetam and levetiracetam, while antagonising pentobarbital action, also inhibit glucose transport. Analeptics like bemigride and methamphetamine are more potent inhibitors of glucose transport than antagonists of hypnotic action on glucose transport. 4 There are similarities between amino-acid sequences in human glucose transport protein isoform 1 (GLUT1) and the benzodiazepine-binding domains of GABAA (gamma amino butyric acid) receptor subunits. Mapped on a 3D template of GLUT1, these homologies suggest that the site of diazepam and piracetam interaction is a pocket outside the central hydrophilic pore region. 5 Nootropic pyrrolidone antagonism of hypnotic drug inhibition of glucose transport in vitro may be an analogue of TRH antagonism of galanin-induced narcosis.

  11. Piracetam and TRH analogues antagonise inhibition by barbiturates, diazepam, melatonin and galanin of human erythrocyte D-glucose transport (United States)

    Naftalin, Richard J; Cunningham, Philip; Afzal-Ahmed, Iram


    Nootropic drugs increase glucose uptake into anaesthetised brain and into Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a chemical structure similar to nootropics increases cerebellar uptake of glucose in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2-oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH antagonise the inhibition of glucose transport by barbiturates, diazepam, melatonin and endogenous neuropeptide galanin in human erythrocytes in vitro. The potencies of nootropic drugs in opposing scopolamine-induced memory loss correlate with their potencies in antagonising pentobarbital inhibition of erythrocyte glucose transport in vitro (PPiracetam and TRH have no direct effects on net glucose transport, but competitively antagonise hypnotic drug inhibition of glucose transport. Other nootropics, like aniracetam and levetiracetam, while antagonising pentobarbital action, also inhibit glucose transport. Analeptics like bemigride and methamphetamine are more potent inhibitors of glucose transport than antagonists of hypnotic action on glucose transport. There are similarities between amino-acid sequences in human glucose transport protein isoform 1 (GLUT1) and the benzodiazepine-binding domains of GABAA (gamma amino butyric acid) receptor subunits. Mapped on a 3D template of GLUT1, these homologies suggest that the site of diazepam and piracetam interaction is a pocket outside the central hydrophilic pore region. Nootropic pyrrolidone antagonism of hypnotic drug inhibition of glucose transport in vitro may be an analogue of TRH antagonism of galanin-induced narcosis. PMID:15148255

  12. A new barbiturate-based centrosymmetric compound: Joint experimental/DFT investigation of the structural, spectroscopic and surface properties (United States)

    Şen, Fatih; Çapan, İrfan; Dincer, Muharrem; Cukurovali, Alaaddin


    A combined experimental and DFT studies on molecular structure along with spectral investigation on the title compound which is a barbiturate derivative with the formula [C34H40N2O5], 5,5-diethyl-1,3-Bis(2-(3-methyl-3-phenylcyclobutyl)-2-oxoethyl)pyrimidine-2,4,6(1H,3H,5H)-trione, has been reported. The crystal and molecular structures of compound were uncovered by single-crystal X-ray diffraction (SCXRD) technique. The starting geometry was obtained from the X-ray structure determination was optimized using density functional theory (DFT/B3LYP) method with the 6-31G(d) and 6-31G(d, p) basis sets in ground state. From the optimized geometry of the molecule, geometric parameters (bond lengths and bond angles), vibrational assignments and chemical shifts of the title compound have been calculated theoretically and compared with the experimental data(SCXRD, FT-IR and NMR). Molecular Electrostatic Potential (MEP) map and Hirshfeld surfaces of the compound are obtained by using the optimized structures and Crystal Explorer software, respectively.

  13. Does the doctrine of double effect apply to the prescription of barbiturates?Syme vs the Medical Board of Australia. (United States)

    Symons, Xavier


    The doctrine of double effect (DDE) is a principle of crucial importance in law and medicine. In medicine, the principle is generally accepted to apply in cases where the treatment necessary to relieve pain and physical suffering runs the risk of hastening the patient's death. More controversially, it has also been used as a justification for withdrawal of treatment from living individuals and physician-assisted suicide. In this paper, I will critique the findings of the controversial Victorian Civil and Administrative Tribunal (VCAT) hearing Syme vs the Medical Board of Australia In that hearing, Dr Rodney Syme, a urologist and euthanasia advocate, was defending his practice of prescribing barbiturates to terminally ill patients. Syme claimed that he prescribed the drugs with the intention of relieving their existential suffering and not to assist in suicide; he argued that the DDE could be applied. Pace VCAT, I argue that this is an illegitimate application of DDE. I argue that a close scrutiny of Syme's actions reveals that, at the very least, he intended to give patients the option of suicide. He furthermore used what on a traditional definition of DDE would be considered a 'bad' means-the prescription of Nembutal-to achieve a 'good' end-the relief of suffering. The case demonstrates the crucial importance of analysing an agent's 'intention' and the 'effects' of their actions when applying DDE. Ethicists and, indeed, the judiciary need to attend to the ethical complexities of DDE when they assess the applicability of DDE to end of life care. If they fail to do this, the doctrine risks losing its legitimacy as an ethical principle. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Intermediates of Krebs cycle correct the depression of the whole body oxygen consumption and lethal cooling in barbiturate poisoning in rat. (United States)

    Ivnitsky, Jury Ju; Schäfer, Timur V; Malakhovsky, Vladimir N; Rejniuk, Vladimir L


    Rats poisoned with one LD50 of thiopental or amytal are shown to increase oxygen consumption when intraperitoneally given sucinate, malate, citrate, alpha-ketoglutarate, dimethylsuccinate or glutamate (the Krebs cycle intermediates or their precursors) but not when given glucose, pyruvate, acetate, benzoate or nicotinate (energy substrates of other metabolic stages etc). Survival was increased with succinate or malate from control groups, which ranged from 30-83% to 87-100%. These effects were unrelated to respiratory depression or hypoxia as judged by little or no effect of succinate on ventilation indices and by the lack of effect of oxygen administration. Body cooling of comatose rats at ambient temperature approximately 19 degrees C became slower with succinate, the rate of cooling correlated well with oxygen consumption decrease. Succinate had no potency to modify oxygen consumption and body temperature in intact rats. A condition for antidote effect of the Krebs intermediate was sufficiently high dosage (5 mmol/kg), further dose increase made no odds. Repeated dosing of succinate had more marked protective effect, than a single one, to oxygen consumption and tended to promote the attenuation of lethal effect of barbiturates. These data suggest that suppression of whole body oxygen consumption with barbiturate overdose could be an important contributor to both body cooling and mortality. Intermediates of Krebs cycle, not only succinate, may have a pronounced therapeutic effect under the proper treatment regimen. Availability of Krebs cycle intermediates may be a limiting factor for the whole body oxygen consumption in barbiturate coma, its role in brain needs further elucidation.

  15. Interaction between metals and nucleic acids. Part 3. Synthesis and structural studies of copper(II) complexes with Schiff base ligands derived from barbituric acid

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, I.; Gaudemer, A.; Chiaroni, A.; Riche, C.


    Schiff bases have been prepared from 5-formylbarbituric acid and 5-formyl-1,3-dimethyl-barbituric acid and various di- or tri-amines. The structure of the corresponding copper(II) complexes have been established by elemental analysis and spectroscopic methods. The molecular structure of one of the complexes, Cu(DiMeBardpt), was determined by X-ray diffraction. Electrochemical study shows that these complexes are reduced at slightly more negative potentials than the corresponding complexes obtained from uracil, which suggests that these new ligands are better electron-donors.

  16. 3D-QSAR Studies on Barbituric Acid Derivatives as Urease Inhibitors and the Effect of Charges on the Quality of a Model

    Directory of Open Access Journals (Sweden)

    Zaheer Ul-Haq


    Full Text Available Urease enzyme (EC has been determined as a virulence factor in pathogenic microorganisms that are accountable for the development of different diseases in humans and animals. In continuance of our earlier study on the helicobacter pylori urease inhibition by barbituric acid derivatives, 3D-QSAR (three dimensional quantitative structural activity relationship advance studies were performed by Comparative Molecular Field Analysis (CoMFA and Comparative Molecular Similarity Indices Analysis (CoMSIA methods. Different partial charges were calculated to examine their consequences on the predictive ability of the developed models. The finest developed model for CoMFA and CoMSIA were achieved by using MMFF94 charges. The developed CoMFA model gives significant results with cross-validation (q2 value of 0.597 and correlation coefficients (r2 of 0.897. Moreover, five different fields i.e., steric, electrostatic, and hydrophobic, H-bond acceptor and H-bond donors were used to produce a CoMSIA model, with q2 and r2 of 0.602 and 0.98, respectively. The generated models were further validated by using an external test set. Both models display good predictive power with r2pred ≥ 0.8. The analysis of obtained CoMFA and CoMSIA contour maps provided detailed insight for the promising modification of the barbituric acid derivatives with an enhanced biological activity.

  17. Daily isoflurane exposure increases barbiturate insensitivity in medullary respiratory and cortical neurons via expression of ε-subunit containing GABA ARs.

    Directory of Open Access Journals (Sweden)

    Keith B Hengen

    Full Text Available The parameters governing GABAA receptor subtype expression patterns are not well understood, although significant shifts in subunit expression may support key physiological events. For example, the respiratory control network in pregnant rats becomes relatively insensitive to barbiturates due to increased expression of ε-subunit-containing GABAARs in the ventral respiratory column. We hypothesized that this plasticity may be a compensatory response to a chronic increase in inhibitory tone caused by increased central neurosteroid levels. Thus, we tested whether increased inhibitory tone was sufficient to induce ε-subunit upregulation on respiratory and cortical neurons in adult rats. Chronic intermittent increases in inhibitory tone in male and female rats was induced via daily 5-min exposures to 3% isoflurane. After 7d of treatment, phrenic burst frequency was less sensitive to barbiturate in isoflurane-treated male and female rats in vivo. Neurons in the ventral respiratory group and cortex were less sensitive to pentobarbital in vitro following 7d and 30d of intermittent isoflurane-exposure in both male and female rats. The pentobarbital insensitivity in 7d isoflurane-treated rats was reversible after another 7d. We hypothesize that increased inhibitory tone in the respiratory control network and cortex causes a compensatory increase in ε-subunit-containing GABAARs.

  18. New spiro (thio barbiturates based on cyclohexanone and bicyclo [3.1.1]heptan-6-one by nonconcerted [1+5] cycloaddition reaction and their conformational structures

    Directory of Open Access Journals (Sweden)

    N. N. Pesyan


    Full Text Available Crossed-aldol condensation reaction of aromatic aldehydes with ketones such as; acetone and cyclohexanone leads to the efficient formation of cross conjugated α,β-unsaturated ketones in excellent yield. The intermolecular and then intramolecular Michael addition reaction of α,β-unsaturated ketones derived from acetone and cyclohexanone with (thiobarbituric acids lead to synthesis new type of 7,11-diaryl-2,4-diazaspiro[5.5]undecane-1,3,5,9-tetraone and 2,4-diaryl-1'H-spiro[bicyclo[3.3.1]nonane-3,5'-pyrimidine]-2',4',6',9(3'H-tetraone, respectively in good yield. Structure elucidation is carried out by 1H NMR, 13C NMR, FT-IR, UV-Visible, mass spectroscopy and X-ray crystallography techniques. A possible mechanism of the formation is discussed. The structural conformation also demonstrated by coupling constants derived from dihedral angles between vicinal and geminal protons. The 1H NMR spectra of NH protons of spiro compounds derived from barbituric acid show a broad singlet peak instead, these protons in the spiro compounds derived from thiobarbituric acid show two distinct peaks. DOI:

  19. A new synthetic methodology for the preparation of biocompatible and organo-soluble barbituric- and thiobarbituric acid based chitosan derivatives for biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Shahzad, Sohail [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100 (Pakistan); Shahzadi, Lubna [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Mahmood, Nasir [Department of Allied Health Sciences and Chemical Pathology, Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore (Pakistan); Siddiqi, Saadat Anwar [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Rauf, Abdul [Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100 (Pakistan); Manzoor, Faisal; Chaudhry, Aqif Anwar [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Rehman, Ihtesham ur [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan); Department of Materials Science and Engineering, The Kroto Research Institute, The University of Sheffield, North Campus, Broad Lane, Sheffield, S3 7HQ (United Kingdom); Yar, Muhammad, E-mail: [Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000 (Pakistan)


    Chitosan's poor solubility especially in organic solvents limits its use with other organo-soluble polymers; however such combinations are highly required to tailor their properties for specific biomedical applications. This paper describes the development of a new synthetic methodology for the synthesis of organo-soluble chitosan derivatives. These derivatives were synthesized from chitosan (CS), triethyl orthoformate and barbituric or thiobarbituric acid in the presence of 2-butannol. The chemical interactions and new functional motifs in the synthesized CS derivatives were evaluated by FTIR, DSC/TGA, UV/VIS, XRD and {sup 1}H NMR spectroscopy. A cytotoxicity investigation for these materials was performed by cell culture method using VERO cell line and all the synthesized derivatives were found to be non-toxic. The solubility analysis showed that these derivatives were readily soluble in organic solvents including DMSO and DMF. Their potential to use with organo-soluble commercially available polymers was exploited by electrospinning; the synthesized derivatives in combination with polycaprolactone delivered nanofibrous membranes. - Highlights: • Development of a new synthetic methodology • Synthesis of organo-soluble chitosan (CS) derivatives • VERO cells proliferation • Nanofibrous membranes from the synthesized chitosan derivatives and polycaprolactone.

  20. Empirical versus mechanistic modelling: comparison of an artificial neural network to a mechanistically based model for quantitative structure pharmacokinetic relationships of a homologous series of barbiturates. (United States)

    Nestorov, I S; Hadjitodorov, S T; Petrov, I; Rowland, M


    The aim of the current study was to compare the predictive performance of a mechanistically based model and an empirical artificial neural network (ANN) model to describe the relationship between the tissue-to-unbound plasma concentration ratios (Kpu's) of 14 rat tissues and the lipophilicity (LogP) of a series of nine 5-n-alkyl-5-ethyl barbituric acids. The mechanistic model comprised the water content, binding capacity, number of the binding sites, and binding association constant of each tissue. A backpropagation ANN with 2 hidden layers (33 neurons in the first layer, 9 neurons in the second) was used for the comparison. The network was trained by an algorithm with adaptive momentum and learning rate, programmed using the ANN Toolbox of MATLAB. The predictive performance of both models was evaluated using a leave-one-out procedure and computation of both the mean prediction error (ME, showing the prediction bias) and the mean squared prediction error (MSE, showing the prediction accuracy). The ME of the mechanistic model was 18% (range, 20 to 57%), indicating a tendency for overprediction; the MSE is 32% (range, 6 to 104%). The ANN had almost no bias: the ME was 2% (range, 36 to 64%) and had greater precision than the mechanistic model, MSE 18% (range, 4 to 70%). Generally, neither model appeared to be a significantly better predictor of the Kpu's in the rat.

  1. The role of Barbie box sequences as cis-acting elements involved in the barbiturate-mediated induction of cytochromes P450BM-1 and P450BM-3 in Bacillus megaterium. (United States)

    Liang, Q; He, J S; Fulco, A J


    In a previous publication (He, J.-S., and Fulco, A. J. (1991) J. Biol. Chem. 266, 7864-7869), we reported that a 15-17-base pair DNA sequence (designated a Barbie box element) in the 5'-regulatory regions of cytochrome P450BM-1 and P450BM-3 genes from Bacillus megaterium was recognized by a barbiturate-regulated protein. It is now recognized that essentially all eukaryotic and prokaryotic genes whose 5'-flanking regions are known and that encode barbiturate-inducible proteins contain the Barbie box element. A 4-base pair sequence (AAAG) is found in the same relative position in all Barbie box elements. In B. megaterium, mutation of the Barbie box located in the P450BM-1 gene leads to the constitutive synthesis of cytochrome P450BM-1 and a 10-fold increase of expression of Bm1P1, a small gene located upstream of the P450BM-1 gene, that encodes a putative regulatory protein. Mutation of the P450BM-3 Barbie box significantly increased the expression of both P450BM-3 and Bm3P1 (another small gene located upstream of the P450BM-3 gene that encodes a second putative regulatory protein) in response to pentobarbital induction but left the basal levels unaffected. In gel mobility shift assays, Bm3R1, a repressor of the P450BM-3 gene, was found to specifically interact with the Barbie box sequences of the B. megaterium P450 genes. Mutated Barbie boxes showed a decreased binding affinity for Bm3R1 compared to their wild type (unmutated) counterparts. Barbie box sequences were also shown to specifically interact with putative positive regulatory factors of B. megaterium cells. These putative positive factors were induced by pentobarbital and were also present at high levels during late stationary phase of B. megaterium cell cultures grown in the absence of barbiturates. The mutated Barbie box sequences had greater binding affinity for these positive factors than did unmutated Barbie box sequences. DNase I footprinting analysis of the 5'-flanking region of the P450BM-1 gene

  2. The Hydrogen Bonded Structures of Two 5-Bromobarbituric Acids and Analysis of Unequal C5–X and C5–X′ Bond Lengths (X = X′ = F, Cl, Br or Me in 5,5-Disubstituted Barbituric Acids

    Directory of Open Access Journals (Sweden)

    Thomas Gelbrich


    Full Text Available The crystal structure of the methanol hemisolvate of 5,5-dibromobarbituric acid (1MH displays an H-bonded layer structure which is based on N–H∙∙∙O=C, N–H∙∙∙O(MeOH and (MeOHO–H∙∙∙O interactions. The barbiturate molecules form an H-bonded substructure which has the fes topology. 5,5′-Methanediylbis(5-bromobarbituric acid 2, obtained from a solution of 5,5-dibromobarbituric acid in nitromethane, displays a N–H···O=C bonded framework of the sxd type. The conformation of the pyridmidine ring and the lengths of the ring substituent bonds C5–X and C5–X′ in crystal forms of 5,5-dibromobarbituric acid and three closely related analogues (X = X′ = Br, Cl, F, Me have been investigated. In each case, a conformation close to a C5-endo envelope is correlated with a significant lengthening of the axial C5–X′ in comparison to the equatorial C5–X bond. Isolated molecule geometry optimizations at different levels of theory confirm that the C5-endo envelope is the global conformational energy minimum of 5,5-dihalogenbarbituric acids. The relative lengthening of the axial bond is therefore interpreted as an inherent feature of the preferred envelope conformation of the pyrimidine ring, which minimizes repulsive interactions between the axial substituent and pyrimidine ring atoms.

  3. New spiro (thio) barbiturates based on cyclohexanone and bicyclo ...

    African Journals Online (AJOL)

    diaryl-1'H-spiro[bicyclo[3.3.1]nonane-3,5'-pyrimidine]-2',4',6',9(3'H)-tetraone, respectively in good yield. Structure elucidation is carried out by 1H NMR, 13C NMR, FT-IR, UV-Visible, mass spectroscopy and X-ray crystallography techniques.

  4. Drug: D04985 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available t ... DG01837 ... Barbiturate sedative-hypnotics ... DG02030 ... Anesthetics ... DG02027 ... General anesthetics ... DG02025 ... Barbiturate anesthetics... ... DG02027 ... General anesthetics ... DG02025 ... Barbiturate anesthetics ... DG02025 ... Barbiturate anesthetics



    Undri Rastuti; Purwati


    Antioxidants are compounds that can delay, retard or inhibit the oxidation reaction. Lignin is a natural polymer consisting of monomeric substituted phenols. Wood lignin degradation Kalba (Albizia falcataria) yields substituted phenol. The purpose of this study was to test the antioxidant activity of compounds of lignin degradation products Kalba using TBA (Thiobarbituric Acid). Wood lignin degradation products Kalba tested antioxidant activity using the TBA method. Phase test phase of this a...

  6. Synthesis and Characterization of Bifunctional Organic-Glasses Based on Diphenylhydrazone and Barbituric Acid Derivative for Photorefractive Application

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ki Hong [KIST, Seoul (Korea, Republic of); Lee, Sang Ho; Choi, Chil Sung; Kim, Nak Joong [Hanyang University, Seoul (Korea, Republic of); Choi, Dong Hoon [Kyunghee University, Youngin (Korea, Republic of)


    A series of amorphous molecules that possess both photoconductive and electro-optic properties was synthesized in order to investigate photorefractive properties of bifunctional organic-glasses. Diethylaminobenzaldehyde- diphenylhydrazone was covalently attached to 5-(4-diethylamino-benzylidene)-1,3-dimethylpyrimidine- 2,4,6-trione through a flexible alkyl chain (3, 4, 5, 6 and 10 carbons) containing two ether linkages. The longer linkage not only lowered the glass transition temperature (Tg) of the molecules, but also allowed faster orientation of the chromophore. To examine the photorefractive properties, a 50 μm-thick film was prepared from the mixture of a bifunctional molecule, butyl benzyl phthalate, and C{sup 60}. The photoconductivity of this composite was as high as 8.01 x 10{sup -12} S/cm at 60 V/μm, and the maximum diffraction efficiency (ηmax) of 50 μm-thick film was about 5% at 80 V/μm.

  7. Free radicals in pyrimidines: ESR of. gamma. -irradiated 5-cyclohexenyl-1,5-dimethyl barbituric acid. [/sup 60/Co

    Energy Technology Data Exchange (ETDEWEB)

    Benson, B. (Lehigh Univ., Bethlehem, PA); Erich, L.


    ESR studies have determined that ionizing radiation damage of hexobarbital (5-cyclohexenyl-1,5-dimethylbarbituric acid) causes the formation of a free radical (A) by hydrogen abstraction from the cyclohexenyl group. Hyperfine coupling tensors were determined for coupling of the unpaired electron to four protons. Visible light of wavelengths near 450 nm reversibly converts this radical to a second free radical (B) which also has the unpaired electron localized in the cyclohexenyl group. The activation energy for a thermally induced reverse conversion (B ..-->.. A) was determined to be 1.4 eV.


    Directory of Open Access Journals (Sweden)

    Undri Rastuti


    Full Text Available Antioxidants are compounds that can delay, retard or inhibit the oxidation reaction. Lignin is a natural polymer consisting of monomeric substituted phenols. Wood lignin degradation Kalba (Albizia falcataria yields substituted phenol. The purpose of this study was to test the antioxidant activity of compounds of lignin degradation products Kalba using TBA (Thiobarbituric Acid. Wood lignin degradation products Kalba tested antioxidant activity using the TBA method. Phase test phase of this antioxidant activity is sample preparation, determination of the maximum wavelength, determination of equilibrium time, absorbance measurements and determination of the percentage of inhibition. The wavelength maximum for BHT test solution was obtained at 530 nm. The stability of absorbance achieved after 80 minutes equilibrium time. BHT test solution and sample solution containing the degradation of lignin 0.10% (w/v increased but not as sharp as the absorbance of control, this suggests that the degradation of wood lignin Kalba have activity as an antioxidant, which relative minimize 13,70 % compare with BHT.

  9. Drug: D00712 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available .gif ... Neuropsychiatric agent ... DG01837 ... Barbiturate sedative-hypnotics ... DG02030 ... Anesthetics ... DG02027 ... General anesthetics... ... DG02025 ... Barbiturate anesthetics ... DG02027 ... General anesthetics ... DG02025 ... Barbiturate anesthetics... ... DG02025 ... Barbiturate anesthetics ATC code: N01AF01 N05CA15 Chemical gr

  10. Dgroup: DG01377 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available P17) ... Neuropsychiatric agent ... DG01837 ... Barbiturate sedative-hypnotics ... DG01567 ... GABA-A receptor agonist ... DG02030 ... Anesthetics... ... DG02027 ... General anesthetics ... DG02025 ... Barbiturate anesthetics ... DG02027 ... General anesthetics... ... DG02025 ... Barbiturate anesthetics ... DG02025 ... Barbiturate anesthetics ... Ba

  11. Dgroup: DG00790 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available (JP17/USP/INN) ... Neuropsychiatric agent ... DG01837 ... Barbiturate sedative-hypnotics ... DG02030 ... Anesthetics ... D...G02027 ... General anesthetics ... DG02025 ... Barbiturate anesthetics ... DG02027 ... General anesthetics ... DG02025 ... Barbiturate anesthetics... ... DG02025 ... Barbiturate anesthetics ATC code: N01AF03 N05CA19 General anesthetics ...

  12. Dgroup: DG00789 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available hohexital sodium (USP) ... Neuropsychiatric agent ... DG01837 ... Barbiturate sedative-hypnotics ... DG02030 ... Anesthetics... ... DG02027 ... General anesthetics ... DG02025 ... Barbiturate anesthetics ... DG02027 ... General anesthetics ... DG020...25 ... Barbiturate anesthetics ... DG02025 ... Barbiturate anesthetics ATC code: N01AF01 N05CA15 General anesthetics ...

  13. 29 CFR Appendix A to Subpart T to... - Examples of Conditions Which May Restrict or Limit Exposure to Hyperbaric Conditions (United States)


    ... or drug use. Conditions requiring continuous medication for control (e.g., antihistamines, steroids, barbiturates, moodaltering drugs, or insulin). Meniere's disease. Hemoglobinopathies. Obstructive or...

  14. Pentobarbital overdose (United States)

    ... Pentosol overdose; Sopental overdose; Repocal overdose; Barbiturate overdose - pentobarbital ... Pentobarbital ... Pentobarbital is the generic name for the following medicines: Nembutal Pentosol Repocal Sopental

  15. The epoxide-diol pathway in the metabolism of vinylbital in rat and man

    NARCIS (Netherlands)

    Vermeulen, N P; Bakker, B H; Eylers, D; Breimer, D D

    1. In urine of rats given vinylbital (5-vinyl-5-(1'-methylbutyl)barbituric acid) i.p., unchanged vinylbital and its devinylated metabolite, 5-(1'-methylbutyl)barbituric acid, were identified. Rats synthetic 1',2'-epoxyvinylbital excreted the same compound as a major metabolite. No unchanged epoxide,

  16. Synthesis and in vivo evaluation of 5-chloro-5-benzobarbiturates as new central nervous system depressants

    Energy Technology Data Exchange (ETDEWEB)

    Vieira, Andreia A.; Gomes, Niele M.; Matheus, Maria E.; Figueroa-Villar, Jose D., E-mail: figueroa@ime.eb.b [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil). Dept. de Chemistry. Medicinal Chemistry Grupo; Fernandes, Patricia D. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Ciencias Biomedicas. Lab. de Farmacologia da Inflamacao e do Oxido Nitrico


    A new family of barbiturates, 5-chloro-5-benzylbarbituric acids, was prepared using a simple efficient synthetic method from aromatic aldehydes and barbituric acid, followed by reduction and chlorination with trichloro-isocyanuric acid, affording overall yields of 53 to 70%. The in vivo evaluation with mice showed that these compounds present tranquilizing activity. (author)

  17. Drug and poison information - the Tygerberg experience

    African Journals Online (AJOL)

    100. TABLE VI. Pharmacotherapy consultations. Drug categories. Antimicrobial. Cardiovascular. Anti-epileptic. Neuroleptic and anti-histamine. Antidepressant. Benzodiazepines, barbiturates and other sedative hypnotics. Respiratory. Miscellaneous. Total. 1986 - 1988. 1990 - 1991. No. %. No. %. Average (%). 312. 29,1.

  18. Efficient Synthesis of Spirobarbiturates and Spirothiobarbiturates Bearing Cyclopropane Rings by Rhodium(II)-Catalyzed Reactions of Cyclic Diazo Compounds

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xue; Lee, Yong Rok [Yeungnam Univ., Gyeongsan (Korea, Republic of)


    Rhodium(II)-catalyzed reactions of cyclic diazo compounds derived from barbituric acid and thiobarbituric acid with a variety of styrene moieties were examined. These reactions provide rapid synthetic routes to the preparations of spirobarbiturates and spirothiobarbiturates bearing cyclopropane rings.

  19. Bibliography [On Drugs]. (United States)

    National Association of Student Personnel Administrators, Detroit, MI.

    A bibliography of materials on drugs is presented. The book and paper back entries are annotated. Selected technical references are listed under these major findings: (1) dependency, (2) barbiturates, (3) amphetamines, and (4) general pharmacology. (PS)

  20. Bone Densitometry (Bone Density Scan) (United States)

    ... Dilantin and certain barbiturates, or high-dose thyroid replacement drugs. have type 1 (formerly called juvenile or ... vertebral fractures that is performed on the DEXA machine, may be recommended for older patients, especially if: ...

  1. Non-covalent synthesis of organic nanostructures

    NARCIS (Netherlands)

    Prins, L.J.; Timmerman, P.; Reinhoudt, David


    This review describes the synthesis, characterization and functionalization of hydrogen bonded, box-like assemblies. These assemblies are formed upon mixing bismelamine calix[4]arenes with a complementary barbiturate in apolar solvents. Various techniques for the characterization have been used,

  2. Trends in CNS affecting drugs in the calls to the Toxicological Information Center from 1997 to 2012

    Czech Academy of Sciences Publication Activity Database

    Urban, M.; Navrátil, Tomáš; Pelclová, D.


    Roč. 34, Suppl 2 (2013), s. 25-30 ISSN 0172-780X Institutional support: RVO:61388955 Keywords : barbiturates * benzodiazepines * poisoning Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 0.935, year: 2013

  3. Benzodiazepines (United States)

    ... with amnesia, hostility, irritability, and vivid or disturbing dreams. Affect on body Benzodiazepines slow down the central nervous system and may cause sleepiness. Drugs causing similar effects Alcohol, barbiturates, sleeping pills, and GHB Overdose effects ...

  4. Dgroup: DG02025 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available DG02025 DGroup Barbiturate anesthetics ... DG00789 ... Methohexital ... D04985 ... Methohexit...iamylal sodium (JP17) ... Neuropsychiatric agent ... DG02030 ... Anesthetics ... DG02027 ... General anesthetics... ... DG02027 ... General anesthetics ATC code: N01AF General anesthetics ...

  5. Neuronal Correlates of Pitch in the Inferior Colliculus

    National Research Council Canada - National Science Library

    Depireux, Didier A; Klein, David J; Simon, Jonathan Z; Shamma, Shihab A


    ...) in the barbiturate- or ketamine-anesthetized ferret were recorded with single tungsten electrodes. Single-unit action potentials were recorded using glassinsulated tungsten microelectrodes with 5 to 6 megohm impedance...

  6. Organization of Response Areas in Ferret Primary Auditory Cortex

    National Research Council Canada - National Science Library

    Shamma, S. A; Fleshman, J. W; Wiser, P. R; Versnel, H


    ...) in the barbiturate- auesthetized ferret. Using a two-tone stimulus, the excitatory and inhibitory portious of the response areas were determined and then parametrized in terms of an asymmetry index...

  7. Cyclosporin in steroid- resistant nephrotic syndrome

    African Journals Online (AJOL)


    Nov 11, 1994 ... infections, impaired hepatic, renal or neurological function, concomitant therapy with nephrotoxic agents, cytostatics, ketoconazole, phenytoin, barbiturates, rifampicin, isoniazid or steroids, malabsorption, cancer, end-stage irreversible renal disease, diabetes mellitus, uncontrolled hypertension and drug or ...

  8. Depressants (United States)

    ... system. Doctors use them to treat things like insomnia or anxiety . But if depressant drugs (like sedatives, tranquilizers, or barbiturates) are abused, they can cause addiction , serious injury, or death. Depressants are usually ...

  9. Trimethobenzamide (United States)

    ... Trimethobenzamide is in a class of medications called antihistamines. Trimethobenzamide may work by decreasing activity in the ... sure to mention any of the following: antidepressants; antihistamines; barbiturates such as phenobarbital (Luminal); belladonna alkaloids (Donnatal); ...

  10. PT and INR Test (United States)

    ... as alcohol, can affect the PT and INR tests. Some antibiotics can increase the PT and INR. Barbiturates, oral ... Time ; Fibrinogen ; Coagulation Factors ; Platelet Count ; Platelet Function Tests ; Thrombin Time ; Warfarin Sensitivity Testing Conditions: Bleeding Disorders , Excessive Clotting Disorders , Vitamin ...

  11. Modification of active BAU and SKT-6A coal types in order to produce a sorbent for hemosorption

    Energy Technology Data Exchange (ETDEWEB)

    Fedoseev, A.S.


    Method is described for obtaining types MKhTI-5u and MKhTI9u modified activated carbon, characterized by large sorption capacity and reduced impurities (sulfur, metals, etc.). Improvement of the modified coal according to luminal and medinal sorption capacity, mechanical strength, sulfur and clinical effectiveness in removing barbituric acid from the blood of patients is discussed. Clinical testing showed its effectiveness in treating patients poisoned by barbituric acid.

  12. Semiautomated radioimmunoassay for mass screening of drugs of abuse

    International Nuclear Information System (INIS)

    Sulkowski, T.S.; Lathrop, G.D.; Merritt, J.H.; Landez, J.H.; Noe, E.R.


    A rapid, semiautomated radioimmunoassay system for detection of morphine, barbiturates, and amphetamines is described. The assays are applicable to large drug abuse screening programs. The heart of the system is the automatic pipetting station which can accomplish 600 pipetting operations per hour. The method uses 15 to 30 μl for the amphetamine and combined morphine/barbiturate assays. A number of other drugs were tested for interference with the assays and the results are discussed

  13. Potential cerebral perfusion agents: synthesis and evaluation of a radioiodinated vinylalkylbarbituric acid analogue

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, P.C.; Callahan, A.P.; Cunningham, E.B.; Knapp, F.F. Jr.


    A new iodinated barbiturate has been prepared. Treatment of 5-chloropentyne and propargyl bromide with diethyl 2-ethyl-2-sodiomalonate (DESM) provided diethyl 2-ethyl-2-(1-pentyn-5-yl)malonate (3) and diethyl 2-ethyl-2-propargylmalonate (4), respectively. Similar condensation of DESM with (E)-(5-iodo-1-penten-1-yl)boronic acid (9) or the reaction of catecholborane with 3 provided diethyl (E)-2-ethyl-2-(1-borono-1-penten-5-yl)malonate (8). The direct sodium iodide-chloramine-T iodination of 8 or the treatment of (E)-1,5-diiodo-1-pentene (10) with DESM provided diethyl (E)-2-ethyl-2-(1-iodo-1-penten-5-yl)malonate (11). The condensation of functionalized malonates 3, 4, and 11 with urea in the presence of a base provided the corresponding barbiturates, 5-ethyl-5-(1-pentyn-5-yl)-(5), 5-ethyl-5-propargyl- (6), and (E)-5-ethyl-5-(1-iodo-1-penten-5-yl)barbituric acid (12), respectively. (E)-6-(Ethoxycarbonyl)-1-iodo-1-octene-6-carboxylic acid (13) was isolated as the hydrolytic byproduct of 11. Compound 13 decarboxylated under vacuum to provide ethyl (E)-1-iodo-1-octene-6-carboxylate (14). The /sup 125/I-labeled congeners of 12 and 13 were synthesized in the same manner and evaluated in rats. The barbiturate 12 exhibited significant brain uptake (approximately 1% dose after 5 min), demonstrating that iodinated barbiturates freely cross the intact blood-brain barrier.

  14. Restrictions in means for suicide: an effective tool in preventing suicide

    DEFF Research Database (Denmark)

    Nordentoft, Merete; Qin, Ping; Helweg-Larsen, Karin


    Restriction of means for suicide is an important part of suicide preventive strategies in different countries. The effect on method-specific suicide rate and overall suicide rate of restrictions on availability of carbon monoxide, barbiturates, and dextropropoxyphene was examined. From 1970 to 2000......, overall suicide mortality and method-specific suicide mortality in Denmark were compared with official information about availability of barbiturates and analgesics and carbon monoxide in vehicle exhaust and household gas. Restrictions on availability of household gas with carbon monoxide content...... and barbiturates was associated with a decline in the number of suicides and suicides by self-poisoning with these compounds after controlling for the effect of calender year. Restricted access occurred concomittantly with a 55 percent decrease in suicide rate....

  15. 5,5-Dihydroxybarbituric acid 1,4-dioxane hemisolvate

    Directory of Open Access Journals (Sweden)

    Thomas Gelbrich


    Full Text Available The asymmetric unit of the title compound,, C4H4N2O5·0.5C4H8O2, contains one molecule of 5,5-dihydroxybarbituric acid with a nearly planar barbiturate ring and half a molecule of 1,4-dioxane. The geometry of the centrosymmetric dioxane molecule is close to an ideal chair conformation. The crystal structure exhibits a complex three-dimensional hydrogen-bonded network. Barbiturate molecules are connected to one another via N—H...O=C, O—H...O=C and N—H...O(hydroxy interactions, while the barbituric acid molecule is linked to dioxane by an O—H...O contact.

  16. Improvements in self-curing composites. (United States)

    Raszewski, Zbigniew; Jałbrzykowski, Marek


    The purpose of this study was to test the influence of a barbituric acid derivative acting as a catalyst and small amounts of pyrolytic silica in acrylic resins on color stability, solubility and sorption of a composite. A series of two-component powder/liquid resin systems were prepared. Monomer-like mixtures (bis-GMA, TEGDMA, tertiary amine 60/40) and a quartz powder with additions of various silica and barbituric acid derivatives were used. Temperature of the material during polymerization was measured with the use of a thermometer. In addition, the material's flexural and compressive strength, sorption and solubility were tested pursuant to ISO4049:2009. The powder-based acrylic composition in a liquid mixed immediately before use, after an addition of a 0.5% barbituric acid derivative, has a lower temperature during the polymerization process (a reduction from 43°C to 37°C), whereas color stability over time is improved, with ΔE=1.81 for samples of powder mixtures containing between 0.45% of BPO and 0.15% of barbituric acid derivatives. For silanized quartz powder with 0.55% BPO and 0.1% BA+0.5% Aerosil R711, the obtained sorption value was 4.57±0.22μg/mm 3 , whereas solubility was 1.60±0.32μg/mm 3 . New catalytic system with barbituric acid derivative, improves color stability for samples stored at room condition and under light of high intensity. A two-phase composite (bis GMA TEGDMA/Quartz), with a new catalytic system with barbituric acid derivatives, has a lower self-cured temperature. Adding a small quantity of hydrophobic silica (0.5%) has a significant influence, with reduced sorption and solubility of the material. Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

  17. Anesthesia for the parturient with cardiovascular disease

    African Journals Online (AJOL)


    myocardial depression and the decreases in SVR that may occur with commonly employed short-acting barbiturates. ... parturients with mitral stenosis; myocardial depression associated with halogenated volatile anesthetics should be ..... and it appears to be inherited as an autosomal dominant trait. The primary features of.

  18. Primary Sjogren's syndrome associated with inappropriate ...

    African Journals Online (AJOL)


    Mar 30, 1990 ... ethanol, paracetamol, barbiturates and benzodiazepines were negative. An ECG, chest radiography, blood gas analysis, thyroid function tests and the cortisol level were norm~ and screening for porphyrin in urine and stool was negative. Computed tomography of the brain and cerebrospinal fluid.

  19. Intraoperative neurophysiological monitoring for the anaesthetist ...

    African Journals Online (AJOL)

    Compound muscle action potentials are abolished by barbiturates, and should be avoided during motor-evoked potential (MEP) monitoring. Although somatosensory-evoked potentials are unaffected by muscle relaxants, they prevent the monitoring of MEPs and should be avoided during multimodal use. When paralysis is ...

  20. The Ro 15-1788 cue: Evidence for benzodiazepine agonist and inverse agonist properties

    NARCIS (Netherlands)

    Vry, J. De; Slangen, J.L.


    Rats discriminating Ro 15–1788 (10 mg/kg, i.p.) from vehicle completely generalized this cue to typical benzodizepines, and partially generalized it to barbiturates, pentylenetetrazol, CGS 8216, β-CCM and PK 8165. CL 218 872, Ro 5–4864, phenytoine, progabide, propranolol, yohimbine and various CNS

  1. Aufbau durch Wasserstoffbrücken zusammengehaltener Nanostrukturen aus 15 Komponenten

    NARCIS (Netherlands)

    Jolliffe, K.A.; Timmerman, P.; Reinhoudt, David


    Insgesamt 72 Wasserstoffbrücken werden bei der spontanen Assoziation von Tetramelamin-Calix[4]arenen und Barbitursäurederivaten zu Nanoaggregaten des schematisch dargestellten Typs gebildet. Diese bestehen aus 15 Komponenten, die vollkommen diastereoselektiv assoziieren: Von acht möglichen

  2. The influence of additives on the morphology and stability of roll-to-roll processed polymer solar cells studied through ex situ and in situ X-ray scattering

    DEFF Research Database (Denmark)

    Zawacka, Natalia Klaudia; Andersen, Thomas Rieks; Andreasen, Jens Wenzel


    -Vis Spectroscopy and Small Angle X-ray Scattering (SAXS) for cells prepared with 1-chloronaphthalene (CN), N-methyl-2-pyrrolidone (NMP) and 1,3-dimethyl-barbituric acid (BARB) as processing additives. The studies suggested that the use of these additives resulted in films with improved morphology and electrical...

  3. Rapid visualization of fingerprints on various surfaces using ZnO superstructures prepared via simple combustion route

    Directory of Open Access Journals (Sweden)

    N.H. Deepthi


    Full Text Available A simple solution combustion route has been used to prepare ZnO nanopowders (NPs using different barbiturates (Barbituric acid, 1, 3-dimethyl barbiturates and 2-thiobarbiturates as fuels. The obtained product was well characterized by powder X-ray diffraction (PXRD, scanning electron microscope (SEM, ultraviolet-visible Spectroscope (UV-Vis and Photoluminescence (PL. The PXRD results confirm the hexagonal phase of the material. The detailed structural analysis is performed by Rietveld refinement method. The energy band gap of NPs is found to be in the range of 3.31 - 3.49 eV. The growth mechanism for the formation of 3D micro-architectures is discussed in detail. The PL emission spectrum shows a broad emission peak at 502 nm upon an 406 nm excitation wavelength. The ZnO NPs can be used for the visualization of latent finger prints (LFPs under normal light on various porous and non-porous surfaces. In this case, the visualized LFPs are found to be excellent compared to the commercially available powders. Keywords: Zinc oxide, Barbiturates, Photoluminescence, Latent fingerprint

  4. A Green One-Pot Synthesis of 4-Hydroxychromenylarylmethyl- 6-Hydroxypyrimidine-2,4-Diones Using Titanium Dioxide Nanowires as an Effective and Recyclable Catalyst. (United States)

    Eskandari, Khalil; Karami, Bahador


    Since a wide range of biological and pharmaceutical activities of barbituric acid, 4-hydroxycoumarin and their derivatives have been disclosed until now, in the domain of our interest to find newly catalytic routes for highly efficient synthesis of potentially interesting biologically active organic compounds, and extension of their areas, herein we introduce a three component combinatorial reaction based on (N,N-dimethyl)barbituric acid and 4- hydroxycoumarin scaffolds. All starting materials were purchased from Merck chemical company and were applied without further purifications. Catalytic reaction between barbituric acid (or N,N-dimethyl barbituric acid), 4-hydroxycoumarin, and a wide range of aryl aldehydes by employing titanium dioxide nanowires (TiO2 NWs) is successfully performed under solvent-free conditions at 100 °C, and led efficiently to obtain target products. From loading above mentioned three component reaction, starting materials in the presence of catalytic amounts of TiO2 NWs as a key factor were condensed together via three C-C bond formation to obtain 12 newly prepared compounds. This procedure profits some advantages such as an efficiency, environmental safety and high recyclability of nano-catalyst. In this work, by the use of a green adapted method in a condensation three component reaction catalyzed by TiO2 NWs as an efficient nano-catalyst, some newly prepared products were prepared in a one pot, and the scope of potentially interesting biologically active organic compounds which can be duly considered by biologists and pharmacologists was developed.

  5. Synthesis and characterization of barbitones as antimicrobial agents

    Directory of Open Access Journals (Sweden)



    Full Text Available Barbitones (3 were synthesised by the condensation of chalcones (2 with barbituric acid. The structure of the synthesized compounds were assigned on the basis of elemental analyses, IR, NMR and mass spectral studies. All the products were evaluated for their in vitro antimicrobial activity against various strains of bacteria and fungi.

  6. Control of structural isomerism in noncovalent hydrogen-bonded assemblies using peripheral chiral information

    NARCIS (Netherlands)

    Prins, L.J.; Jolliffe, K.A.; Hulst, A.J.R.L.; Timmerman, P.; Reinhoudt, David


    The results of a systematic study of the structural isomerism in more than 30 noncovalent hydrogen-bonded assemblies are described. These dynamic assemblies, composed of three calix[4]arene dimelamines and six barbiturates/cyanurates, can be present in three isomeric forms with either D3, C3h, or Cs

  7. Brain carbonic acid acidosis after acetazolamide

    DEFF Research Database (Denmark)

    Heuser, D; Astrup, J; Lassen, N A


    In cats in barbiturate anesthesia extracellular pH and potassium were continously recorded from brian cortex by implanted microelectrodes. Implantation of the electrodes preserved the low permeability of the blood-brain-barrier to HCO3-minus and H+ions as indicated by the development of brain...

  8. Induction of liquid crystallinity of by self-assembled molecular boxes

    NARCIS (Netherlands)

    Piermattei, A.; Giesbers, Marcel; Marcelis, Antonius T.M.; Mendes, Eduardo; Picken, Stephen J.; Crego Calama, Mercedes; Reinhoudt, David


    Jewel-box: In a hierarchical process, three molecules of a calix[4]arene (blue) and six of barbituric or cyanuric acid (green) assemble into double-rosette boxes, which assemble into columns, which in turn assemble into columnar liquid-crystalline phases (see picture). The resulting mesophases have

  9. Structural basis for the catalytic mechanism of a proficient enzyme: Orotidine 5'-Monophosphate Decarboxylase

    DEFF Research Database (Denmark)

    Harris, Pernille Hanne; Poulsen, Jens-Christian Navarro; Jensen, Kaj Frank


    rate by a factor of 1017. This proficiency has been enigmatic, since it is achieved without metal ions or cofactors. Here we present a 2.5 Å resolution structure of ODCase complexed with the inhibitor 1-(5‘-phospho-ß-d-ribofuranosyl)barbituric acid. It shows a closely packed dimer composed of two a...

  10. Supramolecular Control of Oligothienylenevinylene-Fullerene Interactions: Evidence for a Ground-State EDA Complex

    NARCIS (Netherlands)

    McClenaghan, N.D.; Grote, Z.; Darriet, K.; Zimine, M.Y.; Williams, R.M.; De Cola, L.; Bassani, D.M.


    Complementary hydrogen-bonding interactions between a barbituric acid-substituted fullerene derivative (1) and corresponding receptor (2) bearing thienylenevinylene units are used to assemble a 1:1 supramolecular complex ( K ) 5500 M-1). Due to the close proximity of the redox-active moieties within

  11. Self-assembly of a [2 x 2] hydrogen bonded grid

    NARCIS (Netherlands)

    Lipkowski, P.R.; Bielejewska, A.G.; Kooijman, Huub; Spek, Anthony L.; Timmerman, P.; Reinhoudt, David


    Formation of 24 cooperative hydrogen bonds drives the spontaneous assembly of a rigid bifunctional trimelamine and bis(barbituric acid) to give selectively the [2 × 2] hydrogen-bonded grid, in preference to the corresponding [1 × 1] or polymeric assemblies.

  12. Induction of Liquid Crystallinity by Self-Assembled Molecular Boxes

    NARCIS (Netherlands)

    Piermattei, A.; Giesbers, M.; Marcelis, A.T.M.; Mendes, E.; Picken, S.J.; Crego-Calama, M.; Reinhoudt, D.N.


    In a hierarchical process, three molecules of a calix[4]arene (blue) and six of barbituric or cyanuric acid (green) assemble into double-rosette boxes, which assemble into columns, which in turn assemble into columnar liquid-crystalline phases (see picture). The resulting mesophases have a

  13. Single-molecule force-conductance spectroscopy of hydrogen-bonded complexes

    DEFF Research Database (Denmark)

    Pirrotta, Alessandro; De Vico, Luca; Solomon, Gemma C.


    to inform about molecular recognition events at the single-molecule limit. For this, we consider the force-conductance characteristics of a prototypical class of hydrogen bonded bimolecular complexes sandwiched between gold electrodes. The complexes consist of derivatives of a barbituric acid and a Hamilton...

  14. A Novel and Efficient Five-Component Synthesis of Pyrazole Based Pyrido[2,3-d]pyrimidine-diones in Water: A Triply Green Synthesis

    Directory of Open Access Journals (Sweden)

    Majid M. Heravi


    Full Text Available A novel one pot synthesis of pyrazolo[4′,3′:5,6]pyrido[2,3-d]pyrimidine-diones, via a five-component reaction, involving, hydrazine hydrate, ethyl acetoacetate, and 1,3-dimethyl barbituric acid, an appropriate aryl aldehydes and ammonium acetate catalyzed via both of heterogeneous and homogeneous catalysis in water, is reported.

  15. Thermodynamic stabilities of linear and crinkled tapes and cyclic rosettes in melamine-cyanurate assemblies: a model description

    NARCIS (Netherlands)

    Bielejewska, A.G.; Marjo, Christopher E.; Prins, L.J.; Timmerman, P.; de Jong, Feike; Reinhoudt, David


    In this paper we describe model calculations for the self-assembly of N,N-disubstituted melamines 1 and N-substituted cyanuric acid or 5,5-disubstituted barbituric acid derivatives 2 into linear or crinkled tapes and cyclic rosettes via cooperative hydrogen bond formation. The model description

  16. Self-assembly and stability of double rosette nanostructures with biological functionalities

    NARCIS (Netherlands)

    ten Cate, M.G.J.; Omerovic, Merdan; Oshovsky, G.; Crego Calama, Mercedes; Reinhoudt, David


    The syntheses of calix[4]arene dimelamines that are functionalized with alkyl, aminoalkyl, ureido, pyridyl, carbohydrate, amino acid and peptide functionalities, and their self-assembly with barbituric acid or cyanuric acid derivatives into well-defined hydrogen-bonded nanostructures are described.

  17. Noncovalent assembly of a fifteen-component hydrogen-bonded nanostructure

    NARCIS (Netherlands)

    Jolliffe, K.A.; Timmerman, P.; Reinhoudt, David


    A total of 72 hydrogen bonds are formed in the spontaneous association of calix[4]arene tetramelamine and barbituric acid derivatives to give nanosized assemblies of the type represented in the picture. These consist of 15 components that assemble in a completely diastereoselective sense: of the

  18. Synthesis, characterization, antimicrobial activity and molecular ...

    African Journals Online (AJOL)

    Synthesis, characterization, antimicrobial activity and molecular docking studies of combined pyrazol-barbituric acid pharmacophores. Assem Barakat, Bandar M. Al-Qahtani, Abdullah M. Al-Majid, M. Ali Mohammed Rafi Shaik, Mohamed H.M. Al-Agamy, Abdul Wadood ...

  19. ESR study of radiation damage in pyrimidines. Progress report, August 1, 1975--April 1, 1976

    International Nuclear Information System (INIS)

    Benson, B.W.


    The primary objective of this project is to develop general mechanisms for radiation damage to biomolecules using substituted pyrimidines as a model system. Results this year include a single crystal ESR study of 5-ethyl-5-isopropylbarbituric acid, development of the k-band microwave bridge, dose response measurements on methylated barbituric acid derivatives, and synthesis of several specifically deuterated uracil derivatives

  20. Pharmacological modification of sodium channels from the human heart atrium in planar lipid bilayers: electrophysiological characterization of responses to batrachotoxin and pentobarbital

    NARCIS (Netherlands)

    Wartenberg, H. C.; Wartenberg, J. P.; Urban, B. W.


    BACKGROUND AND OBJECTIVE: To investigate the effects of barbiturates on batrachotoxin-modified sodium channels from different regions of the human heart. Single sodium channels from human atria were studied and compared with existing data from the human ventricle and from the central nervous system.

  1. Restrictions in Availability of Drugs Used for Suicide

    DEFF Research Database (Denmark)

    Nordentoft, Merete


    Availability of drugs with high lethality has been hypothesized to increase the risk of self-poisoning suicides. A literature search concerning deliberate self-poisoning and the effect of restricting access to drugs was conducted, and the effect of restrictions in availability of barbiturates, tr...

  2. Diabetes as a risk factor for hepatic encephalopathy in cirrhosis patients

    DEFF Research Database (Denmark)

    Jepsen, Peter; Watson, Hugh; Andersen, Per Kragh


    -diabetic patients using Cox regression, adjusting for gender, age, ascites severity, cirrhosis etiology, Child-Pugh class, creatinine, bilirubin, INR, sodium, potassium, albumin, platelets, lactulose use, benzodiazepine/barbiturate use, spironolactone dose, furosemide dose, potassium-sparing diuretic dose, and Cir...

  3. Synthesis and characterization of 5-heteroarylsulfanyl-4-aryl- 1,2,3 ...

    Indian Academy of Sciences (India)

    the central nervous system and to counteract the effects of over dosage of barbiturates.13 Anti-inflammatory activity is shown by both substituted and unsubstituted tetrazoles.14 A range of cephalosporin derivatives con- taining substituted tetrazole rings has been prepared and found to display antibacterial activity. An active.

  4. [Respiratory depression in delirium tremens patients treated with phenobarbital. A retrospective study

    DEFF Research Database (Denmark)

    Lutzen, L.; Poulsen, L.M.; Ulrichsen, J.


    INTRODUCTION: Delirium tremens (DT) is the most severe manifestation of alcohol withdrawal which--if untreated--has a high rate of mortality. Barbiturates are the most effective drug but respiratory depression may occur. In the present study we investigated the frequency of respiratory problems i...

  5. Drugs of abuse and tranquilizers in Dutch surface waters, drinking water and wastewater: Results of screening monitoring 2009

    NARCIS (Netherlands)

    van der Aa, N.G.F.M.; Dijkman, E.; Bijlsma, L.; Emke, E.; van de Ven, B.M.; van Nuijs, A.L.N.; de Voogt, P.


    In the surface waters of the rivers Rhine and Meuse, twelve drugs that are listed in the Dutch Opium act were detected at low concentrations. They are from the groups amphetamines, tranquilizers (barbiturates and benzodiazepines) opiates and cocaine. During drinking water production, most compounds

  6. Drug: D07321 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ic agent ... DG01837 ... Barbiturate sedative-hypnotics ATC code: N05CA08 ... Barubiturates ... CAS: 2430-49-1 PubChem: 51091658 ChEMBL: CHEMBL2105552 LigandBox: D07321 NIKKAJI: J7.893J ...

  7. U.S. Drug Policy: Shaping Relations With Latin America (United States)


    the public. The misleading ads distributed by the pharmaceutical industry led to extraordinary profits from the barbiturate market . Furthermore, this...WWII AND AFTER, THE SITUATION CHANGES................................63  1.  WWII Market Shifts...Latin America, for instance in the form of Plan Colombia . Distorted success in certain areas gives way to measured failure in the surrounding region

  8. Substance Use by Fourth-Year Students at 13 U.S. Medical Schools. (United States)

    Conard, Scott; And Others


    A study investigated drug use by fourth-year medical students in 13 schools and compared drug use patterns with those of an age- and sex-matched cohort. Medical students reported less use of marijuana, cocaine, cigarettes, LSD, barbiturates, and amphetamines, similar use of opiates, and slightly more use of tranquilizers and alcohol. (MSE)

  9. 21 CFR 522.775 - Doxapram. (United States)


    ... FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS... intravenous use in dogs and cats at a dose of 21/2 to 5 mg per pound (/lb) body weight in barbiturate... be repeated in 15 to 20 minutes if necessary. (2) Indications for use. Administer to dogs, cats, and...

  10. [Fatal poisoning due to narcotic abuse in the analytic-toxicological practice of Forensic Medicine Department Silesian Medical Academy in Katowice in years 1996-202]. (United States)

    Soja, Artur; Celiński, Rafał; Kulikowska, Joanna; Albert, Małgorzata; Sybirska, Halina


    147 cases of fatal poisonings in people due to narcotic abuse examined in the Forensic Medicine Department Silesian School of Medicine, Katowice in the years 1996-2002 have been presented in the paper. In the group examined there were 126 males and 21 females at the age of 16-44. Opium narcotics were found in 139 out of 147 cases and amphetamine derivatives in 18. Opiates were indicated in 58 individuals and amphetamine only in 8. In 35 poisoned people opiates with barbituric acid derivatives were found. In 3 cases death resulted after taking opiates and amphetamine derivatives. 1 individual died after taking opiates and substances of the phenothiazine group. In the organic fluids of 18 people opiates and medicines being derivatives of 1,4-benzodiazepine and barbituric acid were found. Amphetamine and derivatives of 1,4-benzodiazepine were found in 6 individuals and opiates, barbiturates, benzodiazepines and amphetamine in 1 individual. Concentrations of all the substances indicated ranged widely and were as follows: microgram/ml for opiates; microgram/ml for amphetamine; microgram/ml for 1.4-benzodiazepine derivatives and microgram/ml for barbituric acid derivatives. Ethanol was found in 18 individuals and its concentration was @1000.

  11. Substrate Binding Induces Domain Movements in Orotidine 5'-Monophosphate Decarboxylase

    DEFF Research Database (Denmark)

    Harris, Pernille Hanne; Poulsen, Jens-Christian Navarro; Jensen, Kaj Frank


    Orotidine 5'-monophosphate decarboxylase (ODCase) catalyses the decarboxylation of orotidine 5'-monophosphate to uridine 5'-monophosphate (UMP). We have earlier determined the structure of ODCase from Escherichia coli complexed with the inhibitor 1-(5'-phospho-ß- -ribofuranosyl)barbituric acid (BMP...

  12. An interesting spectroscopic method for chromofluorogenic ...

    Indian Academy of Sciences (India)

    Fresh, double-distilled water was used throughout the experiments. Barbituric acid and 4-(N , N-Dimethyl- amino)benzaldehyde were obtained from Merck and. Sigma-Aldrich Co., respectively. Inorganic salts were obtained from Merck Co. The 1H and 13CNMR spectra were recorded on Bruker BioSpin 400 spectrometer at.

  13. 41 CFR Appendix to Part 102 - 74-Rules and Regulations Governing Conduct on Federal Property (United States)


    ... from— (a) Being under the influence, using or possessing any narcotic drugs, hallucinogens, marijuana... alcoholic beverages, narcotic drugs, hallucinogens, marijuana, barbiturates, or amphetamines. Alcoholic..., cultural, educational, or recreational use under the Public Buildings Cooperative Use Act of 1976 (40 U.S.C...

  14. Synthesis and Self-Assembly of Donor–Acceptor–Donor Based Oligothiophenes and Their Optoelectronic Properties

    DEFF Research Database (Denmark)

    Siram, Raja Bhaskar Kanth; Tandy, Kristen; Horecha, Marta


    In this work, the synthesis of an oligothiophene having a donor–acceptor–donor (D–A–D) chromophore with hydrogen bonding groups is described. The D–A–D molecule was demonstrated to self-organize via intermolecular H-bonding between barbituric acid units. Interactions between the oligothiophene...

  15. Kocasli et al., Afr J Tradit Complement Altern Med., (2017) 14 (2 ...

    African Journals Online (AJOL)

    chemotherapy, it has been noted that the use of complementary and alternative therapies (CAT) has been on the rise and that studies in several countries have ... immune system, and increase the toxicity of barbiturates and the hepatotoxic effects of the steroids, amiodarone, methotrexate, ketoconazole and halothane.

  16. 5-[1-(1,3-Dimethyl-2,4,6-trioxohexahydropyrimidin-5-yl-2-oxopropyl]-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H-trione

    Directory of Open Access Journals (Sweden)

    Manfred Steimann


    Full Text Available The title compound, C15H18N4O7, is a product of the substitution reaction of 5,5-dibromo-1,3-dimethylbarbituric acid with sodium sulfide in aqueous acetone. In the crystal, molecules display neither intermolecular nor intramolecular hydrogen bonding and the two barbiturate rings adopt the keto form.

  17. Herbal and alternative medicine: the impact on anesthesia

    African Journals Online (AJOL)

    Sedatives, barbiturates, benzodiazepines, alcohol – en- hanced effect. Blood pressure medications – ginger alters blood pressure and interferes with therapy. Cardiac glycosides – inotropic effect; can alter contractility. Diabetes medications – additive hypoglycaemic effect. Ginkgo. (Ginkgo biloba). Oral – memory loss ...

  18. Antibacterial and antifungal activities of 5-arylidene-n,n-dimethylbarbiturates derivatives

    International Nuclear Information System (INIS)

    Rahim, F.; Haider, S.M.


    A series of N,N-dimethyl-arylidene barbiturates 1-22 has been re-synthesized and evaluated against a number of Gram-positive, Gram-negative bacteria and some fungal strains. Most of the compounds were found to be active against a number of Gram-positive, Gram-negative and also displayed anti-fungal activities. (author)

  19. Reversible and Irreversible Binding of Nanoparticles to Polymeric Surfaces

    Directory of Open Access Journals (Sweden)

    Wolfgang H. Binder


    Full Text Available Reversible and irreversible binding of CdSe-nanoparticles and nanorods to polymeric surfaces via a strong, multiple hydrogen bond (= Hamilton-receptor/barbituric acid is described. Based on ROMP-copolymers, the supramolecular interaction on a thin polymer film is controlled by living polymerization methods, attaching the Hamilton-receptor in various architectures, and concentrations. Strong binding is observed with CdSe-nanoparticles and CdSe-nanorods, whose surfaces are equipped with matching barbituric acid-moieties. Addition of polar solvents, able to break the hydrogen bonds leads to the detachment of the nanoparticles from the polymeric film. Irreversible binding is observed if an azide/alkine-“click”-reaction is conducted after supramolecular recognition of the nanoparticles on the polymeric surface. Thus reversible or irreversible attachment of the nanosized objects can be achieved.

  20. Proficient synthesis of bioactive annulated pyrimidine derivatives: A review

    Directory of Open Access Journals (Sweden)

    Ajmal R. Bhat


    Full Text Available Syntheses of bioactive annulated pyrimidine derivatives are the most significant tasks in N-heterocyclic chemistry because these compounds have proved to be very attractive and useful for the design of new molecular frameworks of potential drugs with varying pharmacological activities. This review paper summarizes the one-pot multicomponent synthesis of annulated nitrogen- and oxygen-containing heterocycles, such as pyrano[2,3-d]pyrimidines, pyrido[2,3-d]pyrimidines and pyrido[2,3-d;5-6-d]dipyrimidines. The synthetic procedure is based on the chemistry of the domino Knoevenagel-Michael addition mechanism. Keywords: Pyrano[2,3-d]pyrimidines, Pyrido[2,3-d]pyrimidines, Pyrido[2,3-d;5-6-d]dipyrimidines, Barbituric acid/Thio-barbituric acid, Aromatic aldehydes, 6-aminouracil

  1. Rubidium 2,4,6-trioxo-1,3-diazinan-5-ide–1,3-diazinane-2,4,6-trione–water (1/1/1

    Directory of Open Access Journals (Sweden)

    Marlena Gryl


    Full Text Available The asymmetric unit of the title compound, Rb+·C4H3N2O3−·C4H4N2O3·H2O, consists of one rubidium cation, a barbituric acid molecule, a barbiturate anion and one water molecule. The rubidium ion has seven close-contact interactions with O atoms, with Rb...O distances ranging from 2.8594 (16 to 3.2641 (14 Å. These seven O atoms together with an eighth O atom at 3.492 (2 Å away from Rb form a distorted polyhedron with shape intermediate between an antiprism and a dodecahedron. The Rb+ ions connect layers built of organic components and water molecules linked via N—H...O and O—H...O hydrogen bonds.

  2. {sup 1} H and {sup 13} C NMR of phenyl barbiturilidene; RMN de H-1 e C-13 de fenil barbiturilidenos

    Energy Technology Data Exchange (ETDEWEB)

    Villar, Jose Daniel Figueroa; Santos, Nedina Lucia dos; Cruz, Elizabete Rangel [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil). Secao de Quimica


    The condensation of barbituric acids with aromatic aldehydes gives the phenyl barbiturilidenes, which are studied as intermediary compounds in the synthesis of new heterocyclic compounds for pharmaceutical use. One of the most characteristic reactions of these compounds is the Michael type addition reaction, in the exocyclic carbon-carbon double binding. The reaction with 2,4-di nitrophenyl hydrazine reaction is been used as a test of this type of reactivity, which supplies the respective hydrazone and barbituric acid. In this work, preliminary studies have been performed for establishing correlations between the Brown parameter ({sigma}{sup +}), the chemical shifts ({delta}) of the barbiturilidene atoms involved in the reaction, and their reactivities 3 refs., 1 fig., 6 tabs.

  3. Evaluation of Fenton's Reagent and Activated Persulfate for Treatment of a Pharmaceutical Waste Mixture in Groundwater

    DEFF Research Database (Denmark)

    Bennedsen, Lars Rønn; Søgaard, Erik Gydesen; Kakarla, Prasad


    Soil and groundwater beneath the Kærgård Plantage megasite in Denmark are contaminated with a complex mixture of pharmaceutical wastes, including sulfonamides, barbiturates, aniline, pyridine chlorinated solvents (DNAPL), benzene, toluene, mercury, and cyanide. Regulatory agencies in Denmark......, cyanide, chromium and other metals both within the aqueous and vapour phases. Except the alkaline activation, all the investigated techniques for activating persulfate were able to remove more than 80% of the primary contaminants. Optimization and more dosages led to 98-99% destruction of primary...... contaminants for both techniques (MFR and ASP). Persulfate activated by MFR also degraded all the analysed barbiturates, sulfonamides, aniline, and pyridine by more than 99.9% or to below detection limits, except sulfonic acid which was reduced by 95%. The main objective of this presentation will be comparison...

  4. Radioimmunoassay screening and GC/MS confirmation of whole blood samples for drugs of abuse

    Energy Technology Data Exchange (ETDEWEB)

    Spiehler, V.R.; Sedgwick, P.

    From 1981 to 1984, an average of 300 radioimmunoassay screens on whole blood were performed each week in the authors laboratory. Most samples were screened for opiates phencyclidine and its analogs, barbiturates, and cocaine or its metabolite benzoylecgonine. A commercially available radioimmunoassay was used with modifications to facilitate screening of whole blood. Increasing sample size increased the sensitivity of the assay. Changing reagent concentration (1:1 dilution), incubation time, sample matrix (water, urine, or blood), or fraction counted (precipitate or supernatant) did not affect the utility of the standard curve or the sensitivity of the assay. All positive results for phencyclidine, opiates, cocaine, and related compounds were confirmed by GC/MA. Barbiturate positives were confirmed by UV spectrophotometry.

  5. N,N-Diethylanilinium 2,4-dioxo-5-(2,4,6-trinitrophenyl-1,2,3,4-tetrahydropyrimidin-6-olate

    Directory of Open Access Journals (Sweden)

    Manickam Buvaneswari


    Full Text Available In the crystal structure of the title molecular salt, C10H16N+·C10H4N5O9−, the components are linked through a N—H...O hydrogen bonds. R22(8 ring motifs are formed between inversion-related barbiturate residues. Two intramoleculer N—H...O hydrogen bonds are observed in the anion. The dihedral angle between 2,4,6-trinitrophenyl and barbiturate rings is 53.6 (2°. The N,N-diethylamine substituent is disordered and was modeled as two geometrically equivalent conformers with occupancies of 0.737 (2 and 0.273 (2.

  6. Portable Tandem Mass Spectrometer Analyzer (United States)


    FILE : MHCI TUNE TABLE 84 (SCANNING with PARENT) SCAN RANGE 10.9 TO 700.0 TUNE MASS 355.0 (AUTO) >LENS 1-3 -13. 88 0. 2: POFF - 1. 2 9: COFF - 4. 1 3...and 500 ng of caffeine in I uL of chloroform by GC/A?:,,MS using negative ions. Also analyzed were barbiturates, extracted from urine, in the 3-5 Mg

  7. E Evalua of Sc ation of chisan f the a dra ch du antioxid hinesis ring ...

    African Journals Online (AJOL)


    emical chara specially its c al., 2008). T meat produc quality and a ay be concer at prevent co meat products ihchoi@joong barbituric acid r remain perma. 014 e ... or in any xtract was sis boiling been accepted tioxidants. Fo rite, butylated ydroxyltoluene e of syntheti due to thei. 96; European n License 4.0 y h d or d e c ir n ...

  8. Enteral Topiramate in a Pediatric Patient with Refractory Status Epilepticus: A Case Report and Review of the Literature


    Shelton, Chasity M.; Alford, Elizabeth L.; Storgion, Stephanie; Wheless, James; Phelps, Stephanie J.


    We describe the use of topiramate in a healthy 12-year-old (88-kg) male who developed refractory generalized convulsive status epilepticus. Seizures persisted despite aggressive use of benzodiazepines (intravenous lorazepam; oral clorazepate), barbiturates (i.e., phenobarbital, pentobarbital), and hydantoins. The child's seizures were controlled with nasogastrically administered topiramate in doses up to 500 mg twice daily (11.4 mg/kg/day). The patient did not display any clinical or laborato...

  9. Thiopentone anaesthesia at Pearl Harbor. (United States)

    Bennetts, F E


    A wartime embargo on casualty figures and an imprecise contemporary editorial contributed to the persisting belief that a grossly excessive mortality rate from barbiturate anaesthesia for surgery of the injured occurred after the Japanese attack on the American bases in Hawaii in December 1941. From accounts by surgical staff and official hospital records which have become available through US Freedom of Information legislation, it is clear that the rumoured death rate from this cause has been greatly exaggerated.

  10. Quantum Chemical and Experimental Studies on the Mechanism of Alkylation of β-Dicarbonyl Compounds. The Synthesis of Five and Six Membered Heterocyclic Spiro Derivatives

    Directory of Open Access Journals (Sweden)

    Ali Hüseyinli


    Full Text Available The alkylation of β-dicarbonyl compounds in a K2CO3/DMSO system wasfound to afford O- and C-alkylated derivatives, depending on the type of the β-dicarbonylcompound involved. The alkyl derivatives obtained were used in the synthesis of some newspiro barbituric acid derivatives. Quantum chemical calculations were carried out toelucidate the reaction mechanisms for some typical synthesis.

  11. BF3/nano-γ-Al2O3 Promoted Knoevenagel Condensation at Room Temperature

    Directory of Open Access Journals (Sweden)

    B. F. Mirjalili


    Full Text Available The Knoevenagel condensation of aromatic aldehydes with barbituric acid, dimedone and malononitrile occurred in the presence of BF3/nano-γ-Al2O3 at room temperature in ethanol. This catalyst is characterized by powder X-ray diffraction (XRD, fourier transform infrared spectroscopy (FT-IR, thermal gravimetric analysis (TGA, field emission scanning electron microscopy (FESEM and energy-dispersive X-ray spectroscopy (EDS.

  12. Not in My Navy. A Legal Guide to Drug Abuse. (United States)


    Today, only about 30 are widely used medically. The barbiturates are armong the most versatile depressant drugs available. They are used for epilepsy ...8217 instructions - but without the knowledge of their associates. For example, such disorders as epilepsy , diabetes, or asthma may require maintenance drug therapy...canna- binoids present in marihuana smoke, i.e., A9-tetrahydrocannabinol (THC), cannabinol, cannabidiol , etc., to excrete their metabolic products in

  13. Benzodiazepine dependence potential: current studies and trends. (United States)

    Smith, D E


    The appearance of newer, short-acting benzodiazepines has produced misconceptions regarding the potential addictive quality of these drugs. Following a review of the Smith and Wesson (1983) barbiturate withdrawal technique, application of this procedure to the withdrawal of individuals addicted to short-acting benzodiazepines is reviewed. Attention is also given to the emergence of "look-alike" drugs, and the resultant implications for substance abuse treatment personnel.

  14. Pharmacologic perturbation as a potential tool to increase the sensitivity of FDG-PET in the evaluation of brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Wong, F.C.L.; Kim, E.E.; Yung, W.K.A. [Univ. of Texas M.D. Anderson Cancer Center, Houston, TX (United States)] [and others


    The usefulness of F-18 FDG PET in the study of brain tumors is limited by the high baseline cortical uptake which decreases the contrast of the tumor. Two alternatives to increase the tumor/background contrast have been reported: barbiturate-induced coma and postprandial state. This project evaluates the effects of sedation with diazepam or of oral glucose intake on the brain tumor/background contrast during F-18 FDG PET studies.

  15. Adverse effects of sympathomimetic drugs in a group of adolescents


    Jerí, F. Raúl; Departamento de Medicina, Sección de Neurología, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú; Carbajal, Carlos; Departamento de Medicina, Sección de Neurología, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú; Sánchez M., César; Departamento de Medicina, Sección de Neurología, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú


    Clinical observations of 35 youths who used hallucinogenic drugs for two to four years are mostly present . The proportion of males was three times compared to women , almost all households were from well integrated and belonged to a higher socio- economic level or medium . The drugs used were marijuana , LSD , barbiturates , mescaline , afetamina , methaqualone and alcohol, in various combinations . All of these young people showed signs of psychological disturbance , personality disorders g...

  16. Changing Spectrum Of Poisoning In Haryana

    Directory of Open Access Journals (Sweden)

    Yadav R.S


    Full Text Available This study involved 1504 patients admitted with acute poisoning (985 males and 519 females with a mean age of 24.5 + -8.3 years, belonging mainly to the rural population (72% and middle income group (65.8%. Aluminum phosphide was the commonest poison ingested followed by Organ phosphorus, Copper Sulphate and Barbiturates. The overall mortality rate was 36.3% and suicidal intent was present most commonly. The underlying socio- economic factors have been discussed.

  17. Cerebral physiology and preservation during cardiac arrest Fisiología y preservación cerebral durante el paro cardíaco: vulnerabilidad del cerebro


    Luis M. Gómez


    Cerebral physiology during cardiac arrest is discussed with particular Interest on selective neuronal damage. Previous concepts on brain tolerance to hypoxia are analyzed and new information about brain function prognosis after cardiac arrest is presented. Therapeutic alternatives for brain preservation are discussed with emphasis on the lack of effectiveness of barbiturates, the results of research with other d...

  18. Beta-Blockers: An Abstracted Bibliography. (United States)


    Biochemistry, Ventilation, Exercise, Human. 600 AUTHORS: Joseph, V. P., Bad rina th, K., Ad Ithan, C., She tty, P. S., and Joseph, T. TITLE: Eftect of...PROCEDURES-: Tested for drug influence on barbiturate hypnosis , anialgesia, anticonvulsant effect, metrazol convulsions, strychnine convulsions, audiogenic...condiLtioned avoid- ance behavior. FINDINGS: Propranolol increased the hypnosis caused by pentobarbital. The drug had no effect on the righting reflex

  19. Download this PDF file

    African Journals Online (AJOL)


    Jun 4, 2005 ... d]pyrimidine-2,4,6(1H,3H)-trione, 10. 3-Cyanochromone 5 (10.0 g, 58 mmole) was dissolved in ethanol (20 mL). Barbituric acid (5.90 g, 46 mmole) and pyridine (3 drops) were added and the resulting mixture refluxed for 6 h. Cooling gave orange precipitate of 10. This was recrystallised from ethanol to give ...

  20. Effect of pomegranate (Punica granutum) and rosemary (Rosmarinus officinalis L.) extracts on shelf-life for chilled Greenland halibut (Reinhardtius hippoglossoides) fillets in modified atmosphere packaging at 2 ºC

    DEFF Research Database (Denmark)

    Ünalan, U.; Dalgaard, Paw; Korel, F.


    ) at 2 °C. Parameters that were monitored were: microbiological (aerobic plate counts (APC), lactic acid bacteria (LAB), Lactobacillus spp., and Photobacterium phosphoreum), biochemical (pH, thio-barbituric acid (TBA), trimethylamine (TMA) and total-volatile-nitrogen (TVN)), and sensory (color, flavor...... days for all samples. The research was supported by the Federation of European Microbiological Societies (FEMS) and performed during a research visit by İlke Uysal Ünalan at DTU Food....

  1. Therapeutic Drug Monitoring of Pentobarbital: Experience at an Academic Medical Center. (United States)

    Humble, Robert M; Ehlers, Alexandra; Pakalniskis, Brittany L; Morris, Cory; Drees, Denny; Kulhavy, Jeff; Krasowski, Matthew D


    Pentobarbital is used for management of intractable seizures and for reducing elevated intracranial pressure. Dosing of pentobarbital can be aided by therapeutic drug monitoring (TDM). There is no commercially available automated assay for measurement of pentobarbital serum/plasma concentrations; consequently, chromatography-based assays are often used. Pentobarbital TDM was studied over a 14-year period at an academic medical center. 154 patients (94 adult, 60 pediatric) were identified who had pentobarbital levels ordered at least once during a hospital encounter. Chart review included patient diagnosis, indication for pentobarbital therapy, recent or concomitant medication with other barbiturates, patient disposition, organ donation, pentobarbital dosing changes, and neurosurgical procedures. Pentobarbital serum/plasma concentrations were determined on an automated clinical chemistry platform with a laboratory-developed test adapted from a urine barbiturates immunoassay. Chart review showed therapeutic use of pentobarbital generally consistent with previously published literature. The most common errors observed involved confusion in barbiturate names (eg, mix-up of pentobarbital and phenobarbital in test ordering or in provider notes) that seemed to have minimal impact on TDM effectiveness, with pentobarbital serum/plasma concentrations generally within target ranges. The laboratory-developed pentobarbital immunoassay showed cross-reactivity with phenobarbital and butalbital that was eliminated by alkaline and heat pretreatment. The immunoassay was linear to 20 mcg/mL and correlated closely with gas chromatography-mass spectrometry measurements at a reference laboratory. Pentobarbital TDM can be performed by immunoassay on an automated clinical chemistry platform, providing an alternative to chromatography-based methods. Confusion in barbiturate names is common, especially pentobarbital and phenobarbital.

  2. ICP management in patients suffering from traumatic brain injury: a systematic review of randomized controlled trials. (United States)

    Abraham, Peter; Rennert, Robert C; Gabel, Brandon C; Sack, Jayson A; Karanjia, Navaz; Warnke, Peter; Chen, Clark C


    Severe traumatic brain injury (sTBI) is a major cause of morbidity and mortality. Intracranial pressure (ICP) monitoring and management form the cornerstone of treatment paradigms for sTBI in developed countries. We examine the available randomized controlled trial (RCT) data on the impact of ICP management on clinical outcomes after sTBI. A systematic review of the literature on ICP management following sTBI was performed to identify pertinent RCT articles. We identified six RCT articles that examined whether ICP monitoring, decompressive craniectomy, or barbiturate coma improved clinical outcomes after sTBI. These studies support (1) the utility of ICP monitoring in the management of sTBI patients and (2) craniectomy and barbiturate coma as effective methods for the management of intracranial hypertension secondary to sTBI. However, despite adequate ICP control in sTBI patients, a significant proportion of surviving patients remain severely disabled. If one sets the bar at the level of functional independence, then the RCT data raises questions pertaining to the utility of decompressive craniectomy and barbiturate coma in the setting of sTBI.

  3. An unusual case of relay pentobarbital toxicosis in a dog. (United States)

    Bischoff, Karyn; Jaeger, Robin; Ebel, Joseph G


    Sodium pentobarbital and phenytoin are common constituents of veterinary euthanasia solutions in the United States. Relay, or secondary, barbiturate toxicosis has been reported in carnivorous animals that have fed from the carcasses of euthanized livestock. This case report presents barbiturate toxicosis in a dog. A 2-year-old female spayed Australian shepherd presented comatose 2 h after ingesting an unknown substance on the beach. The material was retrieved from the stomach by gastric lavage and visually identified as fish or other animal tissue. The dog recovered with symptomatic and supportive therapy and was released on the third day of hospitalization. Tissue found on the beach near where the dog walked and a urine sample from the dog were analyzed by gas chromatography/mass spectrometry. Both samples were positive for pentobarbital and phenytoin. The tissue was consistent with mammalian blubber based on gross and histological examination. Three weeks previously, a juvenile humpback whale had stranded on the beach where the dog had ingested the unknown substance. The whale had been euthanized with a barbiturate solution, necropsied, and removed from the beach. It was not definitively determined that the pentobarbital-containing blubber ingested by the dog was from the euthanized whale, but that was the most likely source. Although attempts were made to remove the whale's remains from the beach, practical considerations made complete removal challenging, if not impossible.

  4. Identification of a molecular target mediating the general anesthetic actions of pentobarbital. (United States)

    Zeller, Anja; Arras, Margarete; Jurd, Rachel; Rudolph, Uwe


    Barbiturates were introduced into medical practice in 1934. They are widely used today as general anesthetics. Although in vitro studies revealed that the activity of a variety of ligand-gated channels is modulated by barbiturates, the target(s) mediating the anesthetic actions of barbiturates in vivo are unknown. Studying pentobarbital action in beta3(N265M) mice harboring beta3-containing GABAA receptors insensitive to a variety of general anesthetic agents, we found that the immobilizing action of pentobarbital is mediated fully, and the hypnotic action is mediated in part by this receptor subtype. It was surprising that the respiratory depressant action of pentobarbital is indistinguishable between beta3(N265M) and wild-type mice and thus is mediated by other as-yet-unidentified targets. Whereas the target for the immobilizing and hypnotic actions of pentobarbital seems to be the same as for etomidate and propofol, these latter agents' respiratory depressant actions are mediated by beta3-containing GABAA receptors. Thus, in contrast to etomidate and propofol, pentobarbital can elicit respiratory depression by a beta3-independent pathway. Pentobarbital reduced heart rate and body temperature to a slightly smaller extent in beta3(N265M) mice compared with wild-type mice, indicating that these actions are largely mediated by other targets. Pentobarbital-induced increase of heart rate variability and prolongation of ECG intervals are seen in both beta3(N265M) mice and wild-type mice, suggesting that they are not dependent on beta3-containing GABAA receptors. In summary, we show a clear pharmacological dissociation of the immobilizing/hypnotic and respiratory/cardiovascular actions of pentobarbital.

  5. Comparison of anaesthetic and kinetic properties of thiobutabarbital, butabarbital and hexobarbital after intravenous threshold doses in the male rat. (United States)

    Koskela, T; Wahlström, G


    Due to the exceptionally long duration of action of thiobutbarbital the anaesthetic properties of this barbiturate was reinvestigated with an intravenous threshold technique using butabarbital and hexobarbital as references. Adult male rats were used. The criterion of anaesthesia was a burst suppression in the EEG of 1 sec. or more (the "silent second" = SS). The dose which induced the criterion was used as a threshold. The barbiturates were infused with different rates to obtain dose rate curves. After induction of the threshold criterion the animals were either killed and different tissue concentrations were analyzed with a HPLC method or allowed to survive and duration of SS and duration of loss of righting reflex were recorded. With hexobarbital, duration of SS and of loss of righting reflex increased significantly with increasing dose rate. With increasing rates of thiobutabarbital and butabarbital there was in both cases a stepwise increase in duration of SS. At sacrifice, after induction of SS with slow rates brain concentrations of both thiobutabarbital and butabarbital were lower than values recorded after higher rates. The change between the two concentrations was abrupt and occurred at a rate of 20 mg/kg/min. with thiobutabarbital and at the rate of 1.25 mg/kg/min. with butabarbital. This phenomenon was the reverse of acute tolerance which was recorded with hexobarbital and can thus be denoted acute supersensitivity. A kinetic analysis of serum, muscle and fat indicated considerable differences between the barbiturates. As indicated by mortality figures the induction of acute supersensitivity could be potentially dangerous.

  6. Increased GABA(A receptor ε-subunit expression on ventral respiratory column neurons protects breathing during pregnancy.

    Directory of Open Access Journals (Sweden)

    Keith B Hengen

    Full Text Available GABAergic signaling is essential for proper respiratory function. Potentiation of this signaling with allosteric modulators such as anesthetics, barbiturates, and neurosteroids can lead to respiratory arrest. Paradoxically, pregnant animals continue to breathe normally despite nearly 100-fold increases in circulating neurosteroids. ε subunit-containing GABA(ARs are insensitive to positive allosteric modulation, thus we hypothesized that pregnant rats increase ε subunit-containing GABA(AR expression on brainstem neurons of the ventral respiratory column (VRC. In vivo, pregnancy rendered respiratory motor output insensitive to otherwise lethal doses of pentobarbital, a barbiturate previously used to categorize the ε subunit. Using electrode array recordings in vitro, we demonstrated that putative respiratory neurons of the preBötzinger Complex (preBötC were also rendered insensitive to the effects of pentobarbital during pregnancy, but unit activity in the VRC was rapidly inhibited by the GABA(AR agonist, muscimol. VRC unit activity from virgin and post-partum females was potently inhibited by both pentobarbital and muscimol. Brainstem ε subunit mRNA and protein levels were increased in pregnant rats, and GABA(AR ε subunit expression co-localized with a marker of rhythm generating neurons (neurokinin 1 receptors in the preBötC. These data support the hypothesis that pregnancy renders respiratory motor output and respiratory neuron activity insensitive to barbiturates, most likely via increased ε subunit-containing GABA(AR expression on respiratory rhythm-generating neurons. Increased ε subunit expression may be critical to preserve respiratory function (and life despite increased neurosteroid levels during pregnancy.

  7. Hypnotic effect of ecdysterone isolated from Pfaffia glomerata (Spreng. Pedersen

    Directory of Open Access Journals (Sweden)

    Raquel Fenner

    Full Text Available In this study the depressant effect of fractions from P. glomerata was initially evaluated using the mice barbiturate sleeping time test as reference. The fractions tested were the CHCl3, the EtOAc, the n-BuOH and the aqueous fraction obtained from P. glomerata subterraneous parts. Only the pretreatment with the lipophilic fraction (CHCl3: EtOAc, 1:1, w/w increased the barbiturate sleeping time (i.p 500 mg/kg; v.o. 1000 mg/kg. Ecdysterone, the main substance isolated from this lipophilic fraction, was identified by spectroscopic methods and its content in the ethanol extract was determined as 1.4% (w/w by HPLC. In order to investigate the hypothesis of ecdysterone displaying a depressant effect on nervous central system, an evaluation toward the hypnotic-sedative and anxiolytic effects of this drug was carried out. Ecdysterone 100 mg/kg, i.p, increased the barbiturate sleeping time without provoking hypothermia; when administered by oral route its minimal effective dose was 400 mg/kg. On the other hand, ecdysterone (100 mg/kg, i.p; 400 mg/kg, p.o did not impair motor coordination and was ineffective on pentylenetetrazole-induced convulsion, elevated plus-maze and step-down inhibitory avoidance tests, indicating that at these doses the drug does not present an anxiolytic profile and does not cause manifest neurotoxic effects as well. In conclusion, the lipophilic fraction from P. glomerata presents a hypnotic effect being ecdysterone one of the compounds responsible for this CNS activity.

  8. Pentobarbital inhibition of human recombinant α1A P/Q-type voltage-gated calcium channels involves slow, open channel block (United States)

    Schober, A; Sokolova, E; Gingrich, KJ


    BACKGROUND AND PURPOSE Pre-synaptic neurotransmitter release is largely dependent on Ca2+ entry through P/Q-type (CaV2.1) voltage-gated Ca2+ channels (PQCCs) at most mammalian, central, fast synapses. Barbiturates are clinical depressants and inhibit pre-synaptic Ca2+ entry. PQCC barbiturate pharmacology is generally unclear, specifically in man. The pharmacology of the barbiturate pentobarbital (PB) in human recombinant α1A PQCCs has been characterized. EXPERIMENTAL APPROACH PB effects on macroscopic Ca2+(ICa) and Ba2+(IBa) currents were studied using whole-cell patch clamp recording in HEK-293 cells heterologously expressing (α1A)human(β2aα2δ-1)rabbit PQCCs. KEY RESULTS PB reversibly depressed peak current (Ipeak) and enhanced apparent inactivation (fractional current at 800 ms, r800) in a concentration-dependent fashion irrespective of charge carrier (50% inhibitory concentration: Ipeak, 656 µM; r800, 104 µM). Rate of mono-exponential IBa decay was linearly dependent on PB concentration. PB reduced channel availability by deepening non-steady-state inactivation curves without altering voltage dependence, slowed recovery from activity-induced unavailable states and produced use-dependent block. PB (100 µM) induced use-dependent block during physiological, high frequency pulse trains and overall depressed PQCC activity by two-fold. CONCLUSION AND IMPLICATIONS The results support a PB pharmacological mechanism involving a modulated receptor with preferential slow, bimolecular, open channel block (Kd = 15 µM). Clinical PB concentrations (<200 µM) inhibit PQCC during high frequency activation that reduces computed neurotransmitter release by 16-fold and is comparable to the magnitude of Ca2+-dependent facilitation, G-protein modulation and intrinsic inactivation that play critical roles in PQCC modulation underlying synaptic plasticity. The results are consistent with the hypothesis that PB inhibition of PQCCs contributes to central nervous system

  9. Butalbital and pediatric headache: stay off the downward path. (United States)

    Caruso, Alessandra; Lazdowsky, Lori; Rabner, Jonathan; Haberman, Jason; LeBel, Alyssa


    Despite limited evidence from the literature surrounding safety or efficacy, butalbital-containing medicines (BCMs) have maintained their rank as "go-to" prescribed migraine and headache relief drugs in the United States, despite bans on these barbiturates in Germany and other European countries. Providers at the Pediatric Headache Program at Boston Children's Hospital recommend that clinicians prescribe triptan-based medications instead of BCMs, given the known negative side effects of BCMs on the general population, and the uncertain longitudinal trajectory of BCMs on developing brains. © 2014 American Headache Society.

  10. Modification of Hewlett-Packard Chemstation (G1034C version C.02.00 and G1701AA version C.02.00 and C.03.00) data analysis program for addition of automatic extracted ion chromatographic groups. (United States)

    Amick, G D


    A modification to data analysis macros to create "ion groups" and add a menu item to the data analysis menu bar is described. These "ion groups" consist of up to 10 ions for extracted ion chromatographs. The present manuscript describes modifications to yield a drop down menu in data analysis that contains user-defined names of groups (e.g., opiates, barbiturates, benzodiazepines) of ions that, when selected, will automatically perform extracted ion chromatographs with up to 10 ions in that group for the loaded datafile.

  11. Enteral topiramate in a pediatric patient with refractory status epilepticus: a case report and review of the literature. (United States)

    Shelton, Chasity M; Alford, Elizabeth L; Storgion, Stephanie; Wheless, James; Phelps, Stephanie J


    We describe the use of topiramate in a healthy 12-year-old (88-kg) male who developed refractory generalized convulsive status epilepticus. Seizures persisted despite aggressive use of benzodiazepines (intravenous lorazepam; oral clorazepate), barbiturates (i.e., phenobarbital, pentobarbital), and hydantoins. The child's seizures were controlled with nasogastrically administered topiramate in doses up to 500 mg twice daily (11.4 mg/kg/day). The patient did not display any clinical or laboratory signs of metabolic acidosis while receiving topiramate. Topiramate should be considered as a treatment option in refractory status epilepticus.

  12. Isomeric indolizine-based π-expanded push-pull NLO-chromophores: Synthesis and comparative study (United States)

    Kalinin, Alexey A.; Yusupova, Gulshat G.; Burganov, Timur I.; Dudkina, Yulia B.; Islamova, Liliya N.; Levitskaya, Alina I.; Khamatgalimov, Ayrat R.; Katsyuba, Sergey A.; Budnikova, Yulia H.; Balakina, Marina Yu.


    Two series of isomeric indolizine-based chromophores with isophorone rings as a π-bridge have been synthesized and systematically investigated. The chromophores have a high thermal stability: the decomposition temperature is above 238 °C. For isomers with 1-methyl-2-phenylindolizin-3-yl (MPI-3) donor group higher values of β are predicted in comparison with those having 3-methyl-2-phenylindolizin-1-yl (MPI-1) donor group. This is in good agreement with the experimental and theoretical values of the HOMO-LUMO energy gap. Indolizine-based chromophores with barbituric acceptor and isophorone moieties in the π-bridge demonstrate the combination of good characteristics.

  13. Pesticide poisoning in the developing world--a minimum pesticides list

    DEFF Research Database (Denmark)

    Eddleston, Michael; Karalliedde, Lakshman; Buckley, Nick


    In parts of the developing world, pesticide poisoning causes more deaths than infectious diseases. Use of pesticides is poorly regulated and often dangerous; their easy availability also makes them a popular method of self-harm. In 1985, the UN Food and Agriculture Organisation (FAO) produced...... to do specific tasks within an integrated pest management system. Use of safer pesticides should result in fewer deaths, just as the change from barbiturates to benzodiazepines has reduced the number of deaths from pharmaceutical self-poisoning....

  14. Process for the reduction of nitrogen oxides in an effluent

    Energy Technology Data Exchange (ETDEWEB)

    Epperly, W.R.; Sullivan, J.C.; Sprague, B.N.


    This patent describes a process for the reduction of the concentration of nitrogen oxides in the effluent from the combustion of a carbonaceous fuel. The process comprises introducing a treatment agent which comprises a composition selected from the group consisting of NH/sub 4/-lignosulfonate, calcium lignosulfonate, 2-furoic acid, 1,3 dioxolane, tetrahydrofuran, furfurylamine, furfurylalcohol, gluconic acid, citric acid, n-butyl acetate, 1,3 butylene glycol, methylal, tetrahydrofuryl alcohol, furan, fish oil, coumalic acid, furfuryl acetate, tetrahydrofuran 2,3,4,5-tetracarboxylic acid, tetrahydrofurylamine, furylacrylic acid, tetrahydropyran, 2,5-furandimethanol, mannitol, hexamethylenediamine, barbituric acid, acetic anhydride, oxalic acid, mucic acid and d-galactose.

  15. The stereochemistry of the condensation product of salicylaldehyde and n-butylbarbituric acid by NMR techniques

    Energy Technology Data Exchange (ETDEWEB)

    Cruz, Elizabete R.; Villar, J. Daniel Figueroa [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil). Dept. de Quimica


    Since the discovery of the 5-deazaflavin cofactor (coenzyme F{sub 420}) as a naturally occurring compound, a great attention has been focused on several iso steric flavin analogues. One of the simplest approaches towards the synthesis of oxadeazaflavin, compound which the nitrogen at the N-10 position of 5-deazaflavin is replaced by oxygen, is the direct condensation between barbituric acid and salicylaldehyde. In this paper, the use of some NMR techniques so as to determine the stereochemistry of the preformed isomer has been described and a possible mechanism for this isomerization discussed 12 refs., 2 figs., 1 tab.

  16. Selenomethionine substitution of orotidine-5-monophosphate decarboxylase causes a change in crystal contacts and space group

    DEFF Research Database (Denmark)

    Poulsen, Jens-Christian Navarro; Harris, Pernille; Jensen, Kaj Frank


    with the inhibitor 1-(5'-phospho- -D-ribofuranosyl)barbituric acid crystallizes under similar conditions as the native enzyme. In contrast to the native enzyme, where the crystals belong to the orthorhombic space group P212121, the SeMet-substituted enzyme crystallizes in the monoclinic space group P21......-wavelength anomalous dispersion technique, both native and SeMet-substituted proteins have been produced and purified. During the production of SeMet ODCase, it was observed that SeMet was the only amino acid that it was necessary to add to the defined medium during expression. SeMet-substituted ODCase in complex...

  17. Polyurethane Foams with Pyrimidine Rings

    Directory of Open Access Journals (Sweden)

    Kania Ewelina


    Full Text Available Oligoetherols based on pyrimidine ring were obtained upon reaction of barbituric acid with glycidol and alkylene carbonates. These oligoetherols were then used to obtain polyurethane foams in the reaction of oligoetherols with isocyanates and water. The protocol of foam synthesis was optimized by the choice of proper kind of oligoetherol and synthetic composition. The thermal resistance was studied by dynamic and static methods with concomitant monitoring of compressive strength. The polyurethane foams have similar physical properties as the classic ones except their enhanced thermal resistance. They stand long-time heating even at 200°C. Moreover thermal exposition of foams results generally in increase of their compressive strength.

  18. Reactions of 3-Formylchromone with Active Methylene and Methyl Compounds and Some Subsequent Reactions of the Resulting Condensation Products

    Directory of Open Access Journals (Sweden)

    M. Lácova


    Full Text Available This review presents a survey of the condensations of 3-formylchromone with various active methylene and methyl compounds, e.g. malonic or barbituric acid derivatives, five-membered heterocycles, etc. The utilisation of the condensation products for the synthesis of different heterocyclic systems, which is based on the ability of the γ-pyrone ring to be opened by the nucleophilic attack is also reviewed. Finally, the applications of microwave irradiation as an unconventional method of reaction activation in the synthesis of condensation products is described and the biological activity of some chromone derivatives is noted.

  19. Tandem Aldol-Michael Reactions in Aqueous Diethylamine Medium: A Greener and Efficient Approach to Bis-Pyrimidine Derivatives

    Directory of Open Access Journals (Sweden)

    Abdullah M. Al-Majid


    Full Text Available A simple protocol, involving the green synthesis for the construction of novel bis-pyrimidine derivatives, 3a–i and 4a–e are accomplished by the aqueous diethylamine media promoted tandem Aldol-Michael reaction between two molecules of barbituric acid derivatives 1a,b with various aldehydes. This efficient synthetic protocol using an economic and environmentally friendly reaction media with versatility and shorter reaction time provides bis-pyrimidine derivatives with high yields (88%–99%.

  20. An efficient synthesis of novel pyrano[2,3-d]- and furopyrano[2,3-d]pyrimidines via indium-catalyzed multi-component domino reaction

    Directory of Open Access Journals (Sweden)

    Gohain Mukut


    Full Text Available Abstract Various novel pyrano [2,3-d]pyrimidines 5 and furopyrano [2,3-d]pyrimidines 7 were synthesized in 80–99% yields via a multicomponent domino Knoevenagel/hetero-Diels-Alder reaction of 1,3-dimethyl barbituric acid with an aromatic aldehyde and ethyl vinyl ether/2,3-dihydrofuran in presence of 1 mol% of indium(III chloride. The reaction also proceeds in aqueous media without using any catalyst, but the yield is comparatively less (65–70%.

  1. A new Ni(II complex as a novel and efficient recyclable catalyst for the synthesis of pyrano[2,3-d]pyrimidines

    Directory of Open Access Journals (Sweden)

    M. Habibi Kheirabadi


    Full Text Available A simple and highly efficient one-pot three-component synthesis of a series of pyrido[2,3-d]pyrimidines from the condensation of barbituric acid, malononitrile and aromatic aldehydes using catalytic amount of a new Ni(II complex based on 5-nitro-N1-((pyridin-2-ylmethylene benzene-1,2-diamine (NiL is reported. This new heterogeneous catalyst has the advantages of being environmentally friendly, simple work-up and high yields character.

  2. Effects of Bright Light Therapy of Sleep, Cognition, Brain Function, and Neurochemistry in Mild Traumatic Brain Injury (United States)


    high very low I like routine adventure I seek the thrill of danger tranquillity I am open to negotiation confrontation I prefer to direct be supervised I...34.        Tranquilizers :  Quaalude, Seconal ("reds"), Valium, Xanax, Librium, Ativan, Dalmane, Halcion, barbiturates,                    Miltown, GHB, Roofinol...Course, Ft. Detrick, MD, U.S. Army Medical Research and Materiel Command[Invited Lecture] 2004 Oral Platform Presentation: Regional cerebral

  3. [Metacommunication in waking and hypnotic states]. (United States)

    Granone, F


    A definition is given of the terms "communication" and "metacommunication", "language" and "metalanguage", and the several types of relationships that may arise in communication: "symmetrical competitive", "integrative complementary", "metacomplementary", and "paradoxical", Reference is made to the "spontaneity" and "simulation" that may arise in communication and metacommunication, during both wakefulness, conscious states in barbituric subnarcosis, and hypnosis. The question of metacommunication during the induction of hypnosis and during the hypnotic relationship is examined, stress being placed on the parapsycholgical metacommunications that may take place during some forms of self- or hetero-induced hypnotic consciousness.

  4. Effectiveness of lorazepam-assisted interviews in an adolescent with dissociative amnesia: A case report★ (United States)

    Seo, Yuna; Shin, Mi-Hee; Kim, Sung-Gon; Kim, Ji-Hoon


    To facilitate gathering information during a psychiatric interview, some psychiatrists advocate augmenting the interview using drugs. Rather than barbiturates, benzodiazepines have been used for drug-assisted interviews. Dissociative amnesia is one of the indications for these interviews. Herein, we present the case of a 15-year-old female who was diagnosed as having dissociative amnesia because of conflicts with her friends. She was administered a lorazepam-assisted interview to aid recovery of her memories. In this case, a small dose of lorazepam was sufficient to recover her memories without any adverse effects. PMID:25206490

  5. Synthesis of some quinazolone derivatives structurally related to certain sedatives and hypnotics. (United States)

    Botros, S; Khalifa, M


    The preparation of certain 3-substituted derivatives of 3.4-dihydro-2-methyl-4-oxoquinazoline is described. The synthesis fo a quinazolone-barbituric acid derivative, in which the two constituting moieties are separated by methylene groups, was achieved by reacting 3-[B-haloethyl]-3.4-dihydro-2-methyl-4-oxoquinazoline with sodio malonic ester and subsequent cyclization of the ester so formed with urea. Attempts to introduce the alpha-glutaryl group at the position 3 of the quinazolone ring system via different routes were unsuccessful.

  6. Crystal structure of 5-[bis(methylsulfonylmethyl]-1,3-dimethyl-5-(methylsulfonylpyrimidine-2,4,6(1H,3H,5H-trione

    Directory of Open Access Journals (Sweden)

    Eyad Mallah


    Full Text Available In the title compound, C10H16N2O9S3, the pyrimidine ring of the 1,3-dimethyl barbituric acid moiety has an envelope conformation with the C atom carrying the methylsulfonyl and bis(methylsulfonylmethyl substituents as the flap. The dihedral angle between mean plane of the pyrimidine ring and the S/C/S plane is 72.4 (3°. In the crystal, molecules are linked via C—H...O hydrogen bonds, forming a three-dimensional structure.

  7. [Respiratory depression in delirium tremens patients treated with phenobarbital. A retrospective study

    DEFF Research Database (Denmark)

    Lutzen, L.; Poulsen, L.M.; Ulrichsen, J.


    INTRODUCTION: Delirium tremens (DT) is the most severe manifestation of alcohol withdrawal which--if untreated--has a high rate of mortality. Barbiturates are the most effective drug but respiratory depression may occur. In the present study we investigated the frequency of respiratory problems...... to ketoacidosis. The death could not be attributed to the phenobarbital treatment. CONCLUSION: In conclusion, we found that the frequency of phenobarbital-induced respiratory depression was low. However, if the DT was complicated with pneumonia, life-threatening respiratory insufficiency could be the outcome...

  8. An effect of phenobarbitone on griseofulvin metabolism in the rat (United States)

    Busfield, Dorothy; Child, K. J.; Tomich, E. G.


    Prior administration of phenobarbitone to male and female rats dosed orally or intravenously with griseofulvin caused a fall in blood levels of the antibiotic. The effect of a single oral dose of phenobarbitone was significant after 12 hr and maximal between 12 and 48 hr, and it lasted for at least 96 hr; it was more pronounced when the barbiturate was administered repeatedly. Liver slices from animals dosed with phenobarbitone metabolized griseofulvin more rapidly than did those from undosed animals. The possible relevance of these findings to the clinical use of griseofulvin is discussed. PMID:14126043

  9. Evaluation of methods of rapid mass killing of segregated early weaned piglets. (United States)

    Whiting, Terry L; Steele, Gregory G; Wamnes, Steinar; Green, Chris


    The operational logistics of mass killing of healthy, surplus piglets by manual blunt force trauma, controlled blunt force trauma, intraperitoneal injection of barbiturate, and free bullet were recorded. Objective performance variables evaluated were, speed of application, human resource and input cost, animal restraint required, and failure rate. Subjective evaluation of esthetics and difficulty of application indicated manual blunt force trauma is an unacceptable technique. Under field conditions, physical methods of killing were superior to intraperitoneal injection of concentrated pentobarbital. Considering animal welfare metrics in isolation, controlled blunt force trauma was superior to all other techniques attempted.

  10. Synthesis of Malononitrile-Condensed Disperse Dyes and Application on Polyester and Nylon Fabrics

    Directory of Open Access Journals (Sweden)

    Yusuf Y. Lams


    Full Text Available An active methylene compound, malononitrile, was introduced into the structures of a series of disperse dyes previously prepared by coupling phloroglucinol, barbituric acid, and α and β-naphtho to 4-amino-3-nitrobenzaldehyde. The dyes were purified by recrystallization from ethanol. The purity of the dyes was examined by thin-layer chromatography (TLC and the dyes were characterized by visible absorption and Fourier transform infrared spectroscopy (FTIR. The malononitrile-condensed dyes produced deeper colours and shades with better fastness to wash, light, and perspiration on application to polyester and nylon fabrics when compared to their uncondensed analogue.

  11. Substance Abuse and Psychiatric Co-morbidity as Predictors of Premature Mortality in Swedish Drug Abusers: A Prospective Longitudinal Study 1970-2006

    DEFF Research Database (Denmark)

    Nyhlén, Anna; Fridell, Mats; Bäckström, Martin


    with a decreased risk. Neurosis, mainly depression and/or anxiety disorders, predicted drug related premature death while chronic psychosis and personality disorders did not. Chronic alcohol addiction was associated with increased risk of non drug related death. Conclusions The cohort of drug abusers had...... an increased risk of premature death to the age of 69. Drug related premature death was predicted by male gender, the use of opiates or barbiturates and depression and anxiety disorders at first admission. The predicted cumulative incidence of drug related death was significantly higher in opiate...

  12. Anesthesia and analgesia in the NICU. (United States)

    Hall, R Whit


    Painful procedures in the neonatal intensive care unit are common, undertreated, and lead to adverse consequences. A stepwise approach to treatment should include pain recognition, assessment, and treatment, starting with nonpharmacologic and progressing to pharmacologic methods for increasing pain. The most common nonpharmacologic techniques include nonnutritive sucking with and without sucrose, kangaroo care, swaddling, and massage therapy. Drugs used to treat neonatal pain include the opiates, benzodiazepines, barbiturates, ketamine, propofol, acetaminophen, and local and topical anesthetics. The indications, advantages, and disadvantages of the commonly used analgesic drugs are discussed. Guidance and references for drugs and dosing for specific neonatal procedures are provided. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. N,N-Diethylanilinium 5-(2,4-dinitrophenyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate

    Directory of Open Access Journals (Sweden)

    Govindan Mangaiyarkarasi


    Full Text Available The asymmetric unit of the title molecular salt, C10H16N+·C10H5N4O7− (trivial name: N,N-diethylanilinium 2,4-dinitrophenylbarbiturate, comprises two anion–cation units. In the anions, the dinitrophenyl ring and the mean plane of the barbiturate ring [planar to within 0.011 (2 and 0.023 (2 Å in the two anions] are inclined to one another by 41.47 (9 and 45.12 (9°. In the crystal, the anions are linked via strong N—H...O hydrogen bonds, forming chains propagating along [10-1]. Within the chains, adjacent inversion-related anionic barbiturate entities are joined through R22(8 ring motifs. The cations are linked to the chains via N—H...O hydrogen bonds. The chains are linked via a number of C—H...O interactions, forming a three-dimensional structure.

  14. Increased release of norepinephrine and dopamine from canine kidney during bilateral carotid occlusion

    International Nuclear Information System (INIS)

    Bradley, T.; Hjemdahl, P.; DiBona, G.F.


    The renal overflow of norepinephrine (NE) and dopamine (DA) to plasma from the innervated kidney was studied at rest and during sympathetic nervous system activation by bilateral carotid artery occlusion (BCO) in vagotomized dogs under barbiturate or barbiturate/nitrous oxide anesthesia. BCO elevated arterial pressure and the arterial plasma concentration of NE, DA, and epinephrine (Epi). Renal vascular resistance (renal arterial pressure kept constant) increased by 15 +/- 7% and the net renal venous outflows (renal veno-arterial concentration difference x renal plasma flow) of NE and DA were enhanced. To obtain more correct estimates of the renal contribution to the renal venous catecholamine outflow, they corrected for the renal extraction of arterial catecholamines, assessed as the extractions of [ 3 H]NE, [ 3 H]DA, or endogenous Epi. The [ 3 H]NE corrected renal NE overflow to plasma increased from 144 +/- 40 to 243 +/- 64 pmol-min -1 during BCO, which, when compared with a previous study of the [ 3 H]NE corrected renal NE overflow to plasma evoked by electrical renal nerve stimulation, corresponds to a 40% increase in nerve impulse frequency from ∼ 0.6 Hz. If the renal catecholamine extraction was not taken into account the effect of BCO was underestimated. The renal DA overflow to plasma was about one-fifth of the NE overflow both at rest and during BCO, indicating that there was no preferential activation of noradrenergic or putative dopaminergic nerves by BCO

  15. Nuclear medicine progress report for quarter ending September 30, 1982

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, F.F. Jr.; Ambrose, K.R.; Butler, T.A.; Goodman, M.M.; Hoeschele, J.D.; Srivastava, P.C.


    In this report a new kit is described for the rapid, regiospecific radioiodination of 15-(p-iodophenyl)pentadecanoic acid (IPP). Iodine-123-labeled IPP is used clinically to monitor myocardial fatty acid metabolism and the new kit offers a major improvement over present methods of radioiodination. During the period three shipments of /sup 191/Os-osmate were made to Medical Cooperative investigators for fabrication of the /sup 191/Os-/sup 191m/Ir radionuclide generator. Five production runs of /sup 11/C labeled amino acids including L-valine, DL-tryptophan and 1-aminocyclohexanecarboxylic acid were synthesized for clinical studies at the Oak Ridge Associated Universities. In addition, seven shipments of /sup 195m/Pt-cis-dichlorodiammineplatinum(II) were made to collaborators for evaluation of the pharmacologic properties of this antitumor agent and to monitor the effective therapeutic dose levels. Several /sup 125/I- and /sup 123m/Te-labeled fatty acids were prepared for evaluation in conjunction with collaborators at the Massachusetts General Hospital. Studies of radioiodinated barbiturates as potential new agents to measure cerebral blood perfusion have also continued. Iodine-125-labeled 5-ethyl-t-(meta-iodophenyl)barbituric acid was prepared as a model agent in which the iodine was stabilized by attachment to a phenyl ring. Evaluation in rats indicated brain uptake with only minimal deiodination. Preliminary studies with tritium-labeled benzo(a)pyrene have also been performed using Syrian hamster embryo (SHE) cells grown in diffusion chambers implanted in rats.

  16. Syntheses, structural elucidation, thermal properties, theoretical quantum chemical studies (DFT and biological studies of barbituric–hydrazone complexes

    Directory of Open Access Journals (Sweden)

    Amina A. Soayed


    Full Text Available Condensation of barbituric acid with hydrazine hydrate yielded barbiturichydrazone (L which was characterized using IR, 1H NMR and mass spectra. The Co(II, Ni(II and Cu(II complexes derived from this ligand have been synthesized and structurally characterized by elemental analyses, spectroscopic methods (IR, UV–Vis and ESR and thermal analyses (TGA, DTG and DTA and the structures were further elucidated using quantum chemical density functional theory. Complexes of L were found to have the ML.nH2O stoichiometry with either tetrahedral or octahedral geometry. The ESR data showed the Cu(II complex to be in a tetragonal geometry. Theoretical investigation of the electronic structure of metal complexes at the TD-DFT/B3LYP level of theory has been carried out and discussed. The fundamental vibrational wavenumbers were calculated and a good agreement between observed and scaled calculated wavenumbers was achieved. Thermal studies were performed to deduce the stabilities of the ligand and complexes. Thermodynamic parameters, such as the order of reactions (n, activation energy ΔE∗, enthalpy of reaction ΔH∗ and entropy ΔS∗ were calculated from DTA curves using Horowitz–Metzger method. The ligand L and its complexes have been screened for their antifungal and antibacterial activities and were found to possess better biological activities compared to those of unsubstituted barbituric acid complexes.

  17. Three-component synthesis of pyrano[2,3-d]-pyrimidine dione derivatives facilitated by sulfonic acid nanoporous silica (SBA-Pr-SO3H and their docking and urease inhibitory activity

    Directory of Open Access Journals (Sweden)

    Ghodsi Mohammadi Ziarani


    Full Text Available A straightforward and efficient method for the synthesis of pyrano[2,3-d]pyrimidine diones derivatives from the reaction of barbituric acid, malononitrile and various aromatic aldehydes using SBA-Pr-SO3H as a nanocatalyst is reported.ResultsReactions proceed with high efficiency under solvent free conditions. Urease inhibitory activity of pyrano[2,3-d]pyrimidine diones derivatives were tested against Jack bean urease using phenol red method. Three compounds of 4a, 4d and 4l were not active in urease inhibition test, but compound 4a displayed slight urease activation properties. Compounds 4b, 4k, 4f, 4e, 4j, 4g and 4c with hydrophobic substitutes on phenyl ring, showed good inhibitory activity (19.45-279.14 muM.DiscussionThe compounds with electron donating group and higher hydrophobic interaction with active site of enzyme prevents hydrolysis of substrate. Electron withdrawing groups such as nitro at different position and meta-methoxy reduced urease inhibitory activity. Substitution of both hydrogen of barbituric acid with methyl group will convert inhibitor to activator.

  18. Nuclear medicine. Progress report for quarter ending June 30, 1982

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, F.F. Jr.; Ambrose, K.R.; Butler, T.A.; Goodman, M.M.; Hoeschele, J.D.; Srivastava, P.C.


    The oxidation products of tellurium and selenium fatty acids were shown to differ and may relate to the unique prolonged retention of tellurium fatty acids in the heart. The studies suggest that the trapping of tellurium fatty acids in the heart may result from the formation of an insoluble oxidation product after entry into the cells of the heart muscle. Also described in this report is the synthesis of several barbituric acid analogues for evaluation as potential cerebral perfusion agents. The present studies indicate that the iodovinyl-alkyl barbiturates cross the intact blood-brain barrier but undergo in vivo deiodination as measured by a high uptake of radioiodine in the thyroid. During this period four /sup 191/Os-osmate shipments were made to Medical Cooperative investigators for evaluation of the ultrashort-lived /sup 191//sup m/Ir (T/sub 1/2/ = 4.9 sec) obtained from the /sup 191//sup m/Ir generator. Seven shipments of the /sup 195//sup m/Pt-labeled cis-dichlorodiammineplatinum(II) antitumor drug were made to collaborators and fice shipments of radiolabeled tellurium fatty acids were made to the Massachusetts General Hospital.

  19. Three-component synthesis of pyrano[2,3-d]-pyrimidine dione derivatives facilitated by sulfonic acid nanoporous silica (SBA-Pr-SO3H and their docking and urease inhibitory activity

    Directory of Open Access Journals (Sweden)

    Ziarani Ghodsi Mohammadi


    Full Text Available Abstract Background A straightforward and efficient method for the synthesis of pyrano[2,3-d]pyrimidine diones derivatives from the reaction of barbituric acid, malononitrile and various aromatic aldehydes using SBA-Pr-SO3H as a nanocatalyst is reported. Results Reactions proceed with high efficiency under solvent free conditions. Urease inhibitory activity of pyrano[2,3-d]pyrimidine diones derivatives were tested against Jack bean urease using phenol red method. Three compounds of 4a, 4d and 4l were not active in urease inhibition test, but compound 4a displayed slight urease activation properties. Compounds 4b, 4k, 4f, 4e, 4j, 4g and 4c with hydrophobic substitutes on phenyl ring, showed good inhibitory activity (19.45-279.14 μM. Discussion The compounds with electron donating group and higher hydrophobic interaction with active site of enzyme prevents hydrolysis of substrate. Electron withdrawing groups such as nitro at different position and meta-methoxy reduced urease inhibitory activity. Substitution of both hydrogen of barbituric acid with methyl group will convert inhibitor to activator.

  20. Structural Characterization of the Molecular Events during a Slow Substrate-Product Transition in Orotidine 5'-Monophosphate Decarboxylase

    Energy Technology Data Exchange (ETDEWEB)

    Fujihashi, Masahiro; Wei, Lianhu; Kotra, Lakshmi P; Pai, Emil F; (TGRI); (Toronto); (Kyoto)


    Crystal structures of substrate-product complexes of Methanobacterium thermoautotrophicum orotidine 5'-monophosphate decarboxylase, obtained at various steps in its catalysis of the unusual transformation of 6-cyano-uridine 5'-monophosphate (UMP) into barbituric acid ribosyl monophosphate, show that the cyano substituent of the substrate, when bound to the active site, is first bent significantly from the plane of the pyrimidine ring and then replaced by an oxygen atom. Although the K72A and D70A/K72A mutants are either catalytically impaired or even completely inactive, they still display bending of the C6 substituent. Interestingly, high-resolution structures of the D70A and D75N mutants revealed a covalent bond between C6 of UMP and the Lys72 side chain after the -CN moiety's release. The same covalent bond was observed when the native enzyme was incubated with 6-azido-UMP and 6-iodo-UMP; in contrast, the K72A mutant transformed 6-iodo-UMP to barbituric acid ribosyl 5'-monophosphate. These results demonstrate that, given a suitable environment, native orotidine 5'-monophosphate decarboxylase and several of its mutants are not restricted to the physiologically relevant decarboxylation; they are able to catalyze even nucleophilic substitution reactions but consistently maintain distortion on the C6 substituent as an important feature of catalysis.

  1. In vivo Piroxicam Metabolites: Possible Source for Synthesis of Central Nervous System (CNS) Acting Depressants. (United States)

    Saganuwan, Saganuwan A


    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. Literature search was carried out with intent to identifying piroxicam metabolites and the possibility of converting them to CNS acting depressants. Piroxicam is convertible to hydroxymethylated metabolite which may be converted to barbiturates such as thiopentone and thiamylal. Whereas cyclodehydrated metabolite may be converted to acetylcyclodehydrated compound that may be in turn converted to acetylacetone and cyclohexamide. However, carboxybenzothiazine metabolite may be converted to carboxamide compound, benzolactone which is convertible to phenazone. Carboxybenzothiazine is also convertible to 2-aminopyridine mepyramine and triplenamine. Conversion of carboxybenzothiazine to gamma aminobutyric acid and phenothiazines such as chlorpromazine, thioridazine, fluphenazine and perphenazine is highly possible. Structurally, barbituric compounds, carboxamide, cyclodehydrated, benzothiazine and carboxybenzothiazine metabolites may act via dopamine and adrenergic receptors causing depression of CNS activities. Piroxicam metabolites may also act via histamine, melatonin and potassium channel receptors causing CNS depression. Copyright© Bentham Science Publishers; For any queries, please email at

  2. Anxiolytic-like effect of Carvacrol (5-isopropyl-2-methylphenol) in mice: involvement with GABAergic transmission. (United States)

    Melo, Francisca Helvira Cavalcante; Venâncio, Edith Teles; de Sousa, Damião Pergentino; de França Fonteles, Marta Maria; de Vasconcelos, Silvânia Maria Mendes; Viana, Glauce Socorro Barros; de Sousa, Francisca Cléa Florenço


    Carvacrol (5-isopropyl-2-methylphenol) is a monoterpenic phenol present in the essencial oil of many plants. It is the major component of the essential oil fraction of oregano and thyme. This work presents the behavioral effects of carvacrol in animal models of elevated plus maze (EPM), open field, Rotarod and barbiturate-induced sleeping time tests in mice. Carvacrol (CVC) was administered orally, in male mice, at single doses of 12.5; 25 and 50 mg/kg while diazepam 1 or 2 mg/kg was used as standard drug and flumazenil (2.5 mg/kg) was used to elucidate the possible anxiolytic mechanism of CVC on the plus maze test. The results showed that CVC, at three doses, had no effect on the spontaneous motor activity in the Rotarod test nor in the number of squares crossed in the open-field test. However, CVC decreased the number of groomings in the open-field test. In the plus maze test, CVC, at three doses significantly increased all the observed parameters in the EPM test and flumazenil was able to reverse the effects of diazepam and CVC. Therefore, CVC did not alter the sleep latency and sleeping time in the barbiturate-induced sleeping time test. These results show that CVC presents anxiolytic effects in the plus maze test which are not influenced by the locomotor activity in the open-field test.

  3. Dynamic CT with brain death

    Energy Technology Data Exchange (ETDEWEB)

    Nakasu, Satoshi; Kodooka, Minoru; Handa, Jyoji (Shiga Univ. of Medical Science, Otsu (Japan))


    Dynamic CT studies were performed on three patients who were diagnosed symptomatically as ''brain-dead'' and on another patient whose EEG was flat due to an overdosage of a barbiturate. Dynamic studies in two of the three patients with presumed brain death revealed no increase in attenuation values, and EEG studies showed no electrical activities of the brain. However, in the one remaining patient whose EEG retained some activity, a dynamic study showed an increase in attenuation values in the circle of Willis. In contrast, the patient whose EEG was flat due to a barbiturate overdosage had a somewhat slowed, but still significant, increase in attenuation values, indicating a decreased but maintained cerebral circulation. Although brain death has been accepted as a concept, no criteria for its diagnosis are widely agreed on, and the necessity for a more refined confirmatory test is increasing. The advantage of this method is that the circulation in the posterior fossa including the brainstem can be evaluated simultaneously if an appropriate slice is selected. Because this method is relatively non-invasive and technically simple, we consider it valuable as an aid in the diagnosis of brain death.

  4. Determination of sedative hypnotics in sewage sludge by pressurized liquid extraction with high-performance liquid chromatography and tandem mass spectrometry. (United States)

    Arbeláez, Paula; Granados, Judith; Borrull, Francesc; Marcé, Rosa Maria; Pocurull, Eva


    This paper describes a method for the determination of eight sedative hypnotics (benzodiazepines and barbiturates) in sewage sludge using pressurized liquid extraction and liquid chromatography with tandem mass spectrometry. Pressurized liquid extraction operating conditions were optimized and maximum recoveries were reached using methanol under the following operational conditions: 100ºC, 1500 psi, extraction time of 5 min, one extraction cycle, flush volume of 60% and purge time of 120 s. Pressurized liquid extraction recoveries were higher than 88% for all the compounds except for carbamazepine (55%). The repeatability and reproducibility between days, expressed as relative standard deviation (n = 5), were lower than 6 and 10%, respectively. The detection limits for all compounds were lower than 12.5 μg/kg of dry weight. The method was applied to determine benzodiazepines and barbiturates in sewage sludge from urban sewage treatment plants, and carbamazepine showed the highest concentration (7.9-18.9 μg/kg dry weight). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Assisted suicide by oxygen deprivation with helium at a Swiss right-to-die organisation. (United States)

    Ogden, Russel D; Hamilton, William K; Whitcher, Charles


    In Switzerland, right-to-die organisations assist their members with suicide by lethal drugs, usually barbiturates. One organisation, Dignitas, has experimented with oxygen deprivation as an alternative to sodium pentobarbital. To analyse the process of assisted suicide by oxygen deprivation with helium and a common face mask and reservoir bag. This study examined four cases of assisted suicide by oxygen deprivation using helium delivered via a face mask. Videos of the deaths were provided by the Zurich police. Dignitas provided protocol and consent information. One man and three women were assisted to death by oxygen deprivation. There was wide variation in the time to unconsciousness and the time to death, probably due to the poor mask fit. Swiss law prevented attendants from effectively managing the face mask apparatus. Purposeless movements of the extremities were disconcerting for Dignitas attendants, who are accustomed to assisting suicide with barbiturates. None of the dying individuals attempted self-rescue. The dying process of oxygen deprivation with helium is potentially quick and appears painless. It also bypasses the prescribing role of physicians, effectively demedicalising assisted suicide. Oxygen deprivation with a face mask is not acceptable because leaks are difficult to control and it may not eliminate rebreathing. These factors will extend time to unconsciousness and time to death. A hood method could reduce the problem of mask fit. With a hood, a flow rate of helium sufficient to provide continuous washout of expired gases would remedy problems observed with the mask.

  6. Control of refractory status epilepticus precipitated by anticonvulsant withdrawal using left vagal nerve stimulation: a case report. (United States)

    Patwardhan, Ravish V; Dellabadia, John; Rashidi, Mahmoud; Grier, Laurie; Nanda, Anil


    To describe a case of left vagal nerve stimulation (VNS) resulting in immediate cessation of status epilepticus (SE) with good neurological outcome. A 30-year-old man with medically intractable seizures including episodes of SE was successfully treated using left VNS. After requiring discontinuation of phenytoin, valproic acid, carbamazepine, and topiramate because of severe allergic reactions resembling Stevens-Johnson syndrome, the patient required pentobarbital coma along with phenobarbital, tiagabine, and levetiracetam for seizure frequency reduction. He underwent left vagal nerve stimulator placement after nearly 9 days of barbiturate-induced coma, with stimulation initiated in the operating room. On the following day, electroencephalography revealed resolution of previously observed periodic lateral epileptiform discharges and the patient was free of seizures. Prestimulation seizure frequency was recorded at 59 times a day, with some seizures enduring 45 minutes despite barbiturate coma. Poststimulation, the patient has been free of seizures for 19 days and is presently taking only levetiracetam and phenobarbital, from which he continues to be successfully weaned without seizures. He is awake, alert, and can recall events leading up to his seizures, with good long-term memory and residual left upper extremity and lower extremity weakness. This case illustrates the role of left vagal stimulation in the treatment of SE and otherwise medically intractable seizures caused by allergic reactions. To our knowledge, this is the first case in the world literature for adults reporting cessation of SE after VNS. Another case with a similar improvement has been reported in the pediatric population.

  7. Synthesis and characterisation of mono-nitrosyl complexes of ruthenium: reactivity of the coordinated nitrosyl

    International Nuclear Information System (INIS)

    Sueur, Stephane


    Within the frame of physical-chemical researches on radioactive effluents, their processing and their evolution, and within the perspective of a possible application to the fixing of radioactive ruthenium, this research thesis reports the study of reactions of barbituric acid with nitro-complexes of ruthenium-nitrosyl. First, the synthesis and the complete study of ketoxime complexes of ruthenium II have been performed. A radio-crystallographic study of HRu(H 2 vi) 3 ,4H 2 O allows the crystallisation of this compound and the molecular structure of Ru(H 2 vi) 3 - to be analysed. Nuclear magnetic resonance has been used to study this ion: the 'cis' structure noticed in solid phase remains present in solution. Spectroscopic studies (IR and FIR) have also been performed to further study the structure and of these tris-chelates. Their stoichiometry and titration have also been studied. The same techniques have then been applied to nitrosyl complexes for their synthesis, characterisation and structural study, and finally to the study of reactions of K 2 RuNOCl 5 and Na 2 RuNo(NO 2 ) 4 OH with barbituric acid

  8. Substance abuse and psychiatric co-morbidity as predictors of premature mortality in Swedish drug abusers a prospective longitudinal study 1970 - 2006

    Directory of Open Access Journals (Sweden)

    Hesse Morten


    Full Text Available Abstract Background Few longitudinal cohort studies have focused on the impact of substances abused and psychiatric disorders on premature mortality. The aim of the present study was to identify predictors of increased risk of drug related death and non drug related death in substance abusers of opiates, stimulants, cannabis, sedatives/hypnotics, hallucinogens and alcohol over several decades. Methods Follow-up study of a consecutive cohort of 561 substance abusers, admitted to a detoxification unit January 1970 to February 1978 in southern Sweden, and followed up in 2006. Demographic and clinical data, substance diagnoses and three groups of psychiatric diagnoses were identified at first admission. Causes of death were coded according to ICD-10 and classified as drug related deaths or non drug related deaths. To identify the incidence of some probable risk factors of drug related premature death, the data were subjected to a competing risks Cox regression analysis. Results Of 561 patients in the cohort, 11 individuals had either emigrated or could not be located, and 204/561 patients (36.4% were deceased by 2006. The cumulative risk of drug related death increased more in the first 15 years and leveled out later on when non drug related causes of death had a similar incidence. In the final model, male gender, regular use of opiates or barbiturates at first admission, and neurosis were associated with an increased risk of drug related premature death, while cannabis use and psychosis were associated with a decreased risk. Neurosis, mainly depression and/or anxiety disorders, predicted drug related premature death while chronic psychosis and personality disorders did not. Chronic alcohol addiction was associated with increased risk of non drug related death. Conclusions The cohort of drug abusers had an increased risk of premature death to the age of 69. Drug related premature death was predicted by male gender, the use of opiates or barbiturates

  9. Anesthesia for pediatric external beam radiation therapy

    International Nuclear Information System (INIS)

    Fortney, Jennifer T.; Halperin, Edward C.; Hertz, Caryn M.; Schulman, Scott R.


    Background: For very young patients, anesthesia is often required for radiotherapy. This results in multiple exposures to anesthetic agents over a short period of time. We report a consecutive series of children anesthetized for external beam radiation therapy (EBRT). Methods: Five hundred twelve children ≤ 16 years old received EBRT from January 1983 to February 1996. Patient demographics, diagnosis, anesthesia techniques, monitoring, airway management, complications, and outcome were recorded for the patients requiring anesthesia. Results: One hundred twenty-three of the 512 children (24%) required 141 courses of EBRT with anesthesia. Anesthetized patients ranged in age from 20 days to 11 years (mean 2.6 ± 1.8 ). The frequency of a child receiving EBRT and requiring anesthesia by age cohort was: ≤ 1 year (96%), 1-2 years (93%), 2-3 years (80%), 3-4 years (51%), 4-5 years (36%), 5-6 years (13%), 6-7 years (11%), and 7-16 years (0.7%). Diagnoses included: primary CNS tumor (28%), retinoblastoma (27%), neuroblastoma (20%), acute leukemia (9%), rhabdomyosarcoma (6%), and Wilms' tumor (4%). Sixty-three percent of the patients had been exposed to chemotherapy prior to EBRT. The mean number of anesthesia sessions per patient was 22 ± 16. Seventy-eight percent of the treatment courses were once daily and 22% were twice daily. Anesthesia techniques included: short-acting barbiturate induction + inhalation maintenance (21%), inhalation only (20%), ketamine (19%), propofol only (12%), propofol induction + inhalation maintenance (7%), ketamine induction + inhalation maintenance (6%), ketamine or short-acting barbiturate induction + inhalation maintenance (6%). Monitoring techniques included: EKG (95%), O 2 saturation (93%), fraction of inspired O 2 (57%), and end-tidal CO 2 (55%). Sixty-four percent of patients had central venous access. Eleven of the 74 children with a central line developed sepsis (15%): 6 of the 11 were anesthetized with propofol (55%), 4 with a

  10. Treatment of depression. (United States)

    Payk, T R


    Depressions are the most common psychiatric diseases. For treatment, plant extracts have been used for thousands of years: examples are extracts from the (sleeping) poppy (opium), deadly nightshade (Atropa belladonna), Indian hemp (hashish), henbane (hyoscyamine), thorn apple (scopolamine), and St. John's wort (hypericum oil). In addition, psychotherapeutic measures, like playing music, dancing, playing theatre, and also the temple sleep, were used. In the 19th century, the introduction of brome (1826), codeine (1832), chloral hydrate (1869), and paraldehyde (1882), as well as the barbiturates (at the turn of the century) introduced significant improvements in pharmacotherapy. The modern thymoleptica therapy started in 1957 with the introduction of imipramine. Now about 40 active antidepressants are marketed. New drug developments should be characterized mainly by an improvement in tolerance.

  11. Legacy of a Chemical Factory Site: Contaminated Groundwater Impacts Stream Macroinvertebrates

    DEFF Research Database (Denmark)

    Rasmussen, Jes J.; McKnight, Ursula S.; Sonne, Anne Thobo


    Legislative and managing entities of EU member states face a comprehensive task because the chemical and ecological impacts of contaminated sites on surface waters must be assessed. The ecological assessment is further complicated by the low availability or, in some cases, absence of ecotoxicity...... data for many of the compounds occurring at contaminated sites. We studied the potential impact of a contaminated site, characterised by chlorinated solvents, sulfonamides, and barbiturates, on benthic macroinvertebrates in a receiving stream. Most of these compounds are characterised by low or unknown...... in the primary inflow zone of the contaminated GW. Moreover, macroinvertebrate communities at these sampling sites could be distinguished from those at upstream control sites and sites situated along a downstream dilution gradient using multidimensional scaling. Importantly, macroinvertebrate indices currently...

  12. Neurophysiological model of the normal and abnormal human pupil (United States)

    Krenz, W.; Robin, M.; Barez, S.; Stark, L.


    Anatomical, experimental, and computer simulation studies were used to determine the structure of the neurophysiological model of the pupil size control system. The computer simulation of this model demonstrates the role played by each of the elements in the neurological pathways influencing the size of the pupil. Simulations of the effect of drugs and common abnormalities in the system help to illustrate the workings of the pathways and processes involved. The simulation program allows the user to select pupil condition (normal or an abnormality), specific site along the neurological pathway (retina, hypothalamus, etc.) drug class input (barbiturate, narcotic, etc.), stimulus/response mode, display mode, stimulus type and input waveform, stimulus or background intensity and frequency, the input and output conditions, and the response at the neuroanatomical site. The model can be used as a teaching aid or as a tool for testing hypotheses regarding the system.

  13. Exposure to an environment containing the aromatic red cedar, Juniperus virginiana: procarcinogenic, enzyme-inducing and insecticidal effects. (United States)

    Sabine, J R


    (1) Shavings from the Eastern Red Cedar (Juniperus virginiana) were examined for three diverse biological properties, i.e. enzyme induction, procarcinogenicity and insecticidal activity. (2) The ability of a cedar environment to stimulate liver drug-metabolizing enzymes in mice was confirmed by lowered values for barbiturate sleeping time. (3) In susceptible strains of mice (C3H-Avy, C3H-AvyfB and CBA/J) the use of cedar shavings as bedding increased significantly the incidence of spontaneous tumors of the liver and mammary gland, and also reduced the average time at which tumors appeared. (4) Cedar and some of its derivatives (Oil of Cedarwood, cedrene, cedrol) disrupted the reproductive and developmental cycle of a number of insects, including the Peanut Trash Bug (Elasmolomus sordidus), the Indian Meal Moth (Plodia interpunctella) and the Forage Mite (Tyrophagus putrescentiae).

  14. The Thermodynamics of General and Local Anesthesia (United States)

    Græsbøll, Kaare; Sasse-Middelhoff, Henrike; Heimburg, Thomas


    General anesthetics are known to cause depression of the freezing point of transitions in biomembranes. This is a consequence of ideal mixing of the anesthetic drugs in the membrane fluid phase and exclusion from the solid phase. Such a generic law provides physical justification of the famous Meyer-Overton rule. We show here that general anesthetics, barbiturates and local anesthetics all display the same effect on melting transitions. Their effect is reversed by hydrostatic pressure. Thus, the thermodynamic behavior of local anesthetics is very similar to that of general anesthetics. We present a detailed thermodynamic analysis of heat capacity profiles of membranes in the presence of anesthetics. This analysis is able to describe experimentally observed calorimetric profiles and permits prediction of the anesthetic features of arbitrary molecules. In addition, we discuss the thermodynamic origin of the cutoff-effect of long-chain alcohols and the additivity of the effect of general and local anesthetics.

  15. Labelling of bleomycin with technetium-99m for diagnosis in nuclear medicine

    International Nuclear Information System (INIS)

    Nassute, J.C.


    A study about the behavior of the labelling yield of an antineoplastic drug (bleomycin) with a short-leved radionuclide ( 99 sup(m) Tc), using An(II) as a reductor agent, is presented. Parameters like the pH in the labelling, influence of the reaction time and mass of tin on the labelling yield were analysed. To simplify the labelling,, a lyofilized kit of Sn(II)/BLM in evacuated vials was prepared. The quality control involving paper chromatography, sterility and 'in vivo' test was made. The 'in vivo' tests were made both in healthy rats and in those with tumorous tissues, under barbituric action. The biological distribution, the concentration time of the products in tumors, the excretion time and excretion via were studied by means of scintigraphy and scintiphotos. (Author) [pt

  16. Comparison of the EEG effects of midazolam, thiopental, and propofol: the role of underlying oscillatory systems. (United States)

    Feshchenko, V A; Veselis, R A; Reinsel, R A


    The EEG effects of 3 intravenous sedative drugs from different chemical families were studied during conscious sedation in 47 normal volunteers. The drugs studied were midazolam (a benzodiazepine), propofol (an alkylphenol) and thiopental (a barbiturate). Though these drugs cause different degrees of amnesia, they have the common EEG effects of suppressing alpha-rhythm and increasing total beta-power. A large portion of the increase in beta-power can be accounted for by beta-rhythms. We used the UNIFAC-EEG technique to differentiate oscillatory systems underlying the rhythms induced by these drugs in a quantitative fashion. While thiopental induced beta-rhythms which were similar to those appearing during drowsiness, midazolam and propofol induced beta-rhythms with substantially different characteristics. The differences between the beta-rhythms induced by drug infusion and previously described 'sleep spindles' are discussed. We conclude that a quantitative analysis of beta-rhythms can differentiate the effects of these drugs on the EEG.

  17. A Study on Brown Seaweed Therapy ( Sargassum sp. toward MDA Levels and Histological Improvement on Rat Foot Suffering Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Fauziah Fauziah


    Full Text Available Rheumatoid arthritis (AR, an autoimun disease, is characterized by the inflammation in the joint area caused an excessive of free radicals. An excessive of free radicals in the body cause oxidative stress, that increasing levels of malondialdehyde (MDA as an indicator of lipid peroxidation and the decreasing levels of anti-oxidants. The treated with extract of brown seaweed (Sargassum sp. intended to find out the MDA levels in serum and the histological of the foot joints rheumatoid arthritis rats. Malondialdehyde levels are determined through a TBA test (Thio Barbituric acid, meanwhile the histological of the rat foot joints was determined by Hematoxylen-Eosin staining (HE. The results showed the brown seaweed extract therapy (Sargassum sp. was significantly (p <0.01 reduce levels of malondialdehyde (MDA in the serum of 21,24% and improving histological foot joints rheumatoid arthritis rats.

  18. Molecular Structure, Spectroscopic and DFT Computational Studies of Arylidene-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H-trione

    Directory of Open Access Journals (Sweden)

    Assem Barakat


    Full Text Available Reaction of barbituric acid derivatives and di-substituted benzaldehyde in water afforded arylidene-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H-trione derivatives (1 and 2. The one step reaction proceeded efficiently, smoothly, and in excellent yield. The arylidene compounds were characterized by spectrophotometric tools plus X-ray single crystal diffraction technique. Quantum chemical calculations were performed using the DFT/B3LYP method to optimize the structure of the two isomers (1 and 2 in the gas phase. The optimized structures were found to agree well with the experimental X-ray structure data. The highest occupied (HOMO and lowest unoccupied (LUMO frontier molecular orbitals analyses were performed and the atomic charges were calculated using natural populationanalysis.

  19. Investigation of the formation of hydrogen cyanide in the coking of kuzbass coal. [Magnitogorsk Integrated Iron and Steel Works-USSR

    Energy Technology Data Exchange (ETDEWEB)

    Grigorev, N.P.; Zhilyaev, Yu.A.; Akulov, P.V.


    The experiments were performed using equipment which practically excluded deep pyrolysis of the vapor gas products. The hydrogen cyanide was recovered with 0.1 N caustic soda solution in the temperature range of 500 to 1000/sup 0/C. The HCN concentration was measured photometrically by the acid derivative formed as a result of the reaction of the cyanide radical with the barbituric acid amines. The dynamics of the HCN yield were investigated as a function of the heating rate, the degree of comminuition of the coal types and the charge. 2/3 of the HCN is formed as a result of pyrolysis of the vapor-gas products and 1/3 is attributed to the thermochemical conversion of organic matter.

  20. EPA (Environmental Protection Agency) Method Study 12, cyanide in water. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Winter, J.; Britton, P.; Kroner, R.


    EPA Method Study 12, Cyanide in Water reports the results of a study by EMSL-Cincinnati for the parameters, Total Cyanide and Cyanides Amendable to Chlorination, present in water at microgram per liter levels. Four methods: pyridine-pyrazolone, pyridine-barbituric acid, electrode and Roberts-Jackson were used by 112 laboratories in Federal and State agencies, municipalities, universities, and the private/industrial sector. Sample concentrates were prepared in pairs with similar concentrations at each of three levels. Analysts diluted samples to volume with distilled and natural waters and analyzed them. Precision, accuracy, bias and the natural water interference were evaluated for each analytical method and comparisons were made between the four methods.

  1. Personal monitors for inorganic gases. Final report, 28 September 1978-31 August 1979

    Energy Technology Data Exchange (ETDEWEB)

    West, P.W.


    Successful passive sampling techniques were developed for ammonia and hydrogen-cyanide. For ammonia the collection of the sample required permeation through a silicone membrane into boric acid. Spectrophotometric determination of the ammonia was carried out using Nessler's reagent or potentiometrical means with an ion-selective electrode. Linearity was demonstrated using the monitor over concentration ranges of less than 10 to over 160 parts per million. The ammonia monitor was relatively free from interference by amines and could be used in a badge-type monitor, as it was very light in weight and compact. The hydrogen-cyanide monitor functioned by permeation through a silicone membrane. The permeated gas was stabilized in sodium hydroxide and determined by means of a standard pyridine/barbituric acid colorimetric method. A detection limit of 10 parts per billion for an 8-hour exposure was obtained. Difficulties were encountered in developing a sampler for hydrogen sulfide.

  2. Fluorescence and amplified spontaneous emission of glass forming compounds containing styryl-4H-pyran-4-ylidene fragment

    Energy Technology Data Exchange (ETDEWEB)

    Vembris, Aivars, E-mail: [Institute of Solid State Physics, University of Latvia, 8 Kengaraga Street, Riga LV-1063 (Latvia); Muzikante, Inta [Institute of Solid State Physics, University of Latvia, 8 Kengaraga Street, Riga LV-1063 (Latvia); Karpicz, Renata; Sliauzys, Gytis [Institute of Physics, Center for Physical Sciences and Technology, A. Gostauto 11, LT-01108 Vilnius (Lithuania); Miasojedovas, Arunas; Jursenas, Saulius [Institute of Applied Research, Vilnius University, Sauletekio 9-III, LT-10222 Vilnius (Lithuania); Gulbinas, Vidmantas [Institute of Physics, Center for Physical Sciences and Technology, A. Gostauto 11, LT-01108 Vilnius (Lithuania)


    Potential of glassy films of newly synthesised low molecular weight organic molecules for light amplification and lasing applications has been investigated by analysing fluorescence, transient differential absorption and amplified spontaneous emission properties. These non-symmetric and symmetric molecules contain styryl-4H-pyran-4-ylidene fragment with three different electron acceptor groups: dicyanomethylene, barbituric acid, indene-1,3-dione. Fluorescence quantum yields of the investigated compounds in solutions are between 0.32 and 0.54, while they drop down by an order of magnitude in thin solid films. Incorporation of bulky side groups reduced excitonic interactions enabling manifestation of amplified spontaneous emission in the neat films of the investigated derivatives. - Highlights: Black-Right-Pointing-Pointer Bulky substituents attached to DCM dye enable formation of neat glassy films. Black-Right-Pointing-Pointer Investigated dyes show amplified spontaneous emission in neat films. Black-Right-Pointing-Pointer Two electron donor groups negatively influence light amplification.


    Directory of Open Access Journals (Sweden)

    N. Sheikh


    Full Text Available Garlic, an antioxidant plant, can react with amino groups of proteins to form Schiff bases. As diabetes leads to glycation of various proteins and this in turn has some effects on the structure of proteins and biochemical activity of them, the inhibition of this process seems very vital. For several years researchers in this field have done their best to recognize the antidiabetic compounds. The aim of this study is to determine the effects of garlic on albumin glycation in vitro.In the presence of various concentrations of garlic, albumin was glycated and evaluated using TBA (thio-barbituric acid method. The results showed that garlic has a statistically significant (P<0.05 effect in inhibiting or decreasing the reaction of albumin glycation. The findings of this research shows that garlic probably inhibits the reaction of glycation and decreases complications occurring in diabetes.

  4. Spectral, magnetic, and thermal properties of some thiazolylazo complexes

    Energy Technology Data Exchange (ETDEWEB)

    Masoud, M. S.; Mohamed, G. B.; Abdulrazek, Y. H.; Ali, A. E. [Alexandria Univ., Alexandria (Egypt); Khairy, F. N. [Ahfad Univ. for Women, Omderman (Sudan)


    The thiazolylazo compounds and their Co(II), Ni(II) and Cu(II) complexes of barbituric acid, uracil, thiouracil, citrazinic acid, chromotropic acid, gallic acid, pyrogallol and salicylic acid were prepared and characterized by {sup 1}H NMR, IR and the effect of pH on the electronic absorption spectra. The mode of ionization, the electronic transitions and the dissociation constants were discussed. The stoichiometries of the complexed were of 1:1, 2:1 and 3:2 (M:L). The copper complexes are of isotropic ESR spectra (except that of gallic acid which showed a complicated one) and are of magnetically diluted behavior with orbital contribution. Detailed DTA data were obtained and discussed.

  5. Analytical method used for intermediate products in continuous distillation of furfural

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Z.L.; Jia, M.; Wang, L.J.; Deng, Y.X.


    During distillation of furfural, analysis of main components in the crude furfural condensate and intermediate products is very important. Since furfural and methylfurfural are homologous and both furfural and acetone contain a carbonyl group, components in the sample must be separated before analysis. An improved analytical method has been studied, the accuracy and precision of which would meet the requirement of industrial standards. The analytical procedure was provided as follows: to determine the furfural content with gravimetric method of barbituric acid; to determine the methanol content with dichromate method after precipitating furfural and acetone, and distilling the liquid for analysis; and to determine the methylfurfural content with bromide-bromate method, which can be used only in the sample containing higher content of methylfurfural. For the sample in low content, the gas-liquid chromatographic method can be used. 7 references.

  6. Physiological antioxidant system and oxidative stress in stomach cancer patients with normal renal and hepatic function

    Directory of Open Access Journals (Sweden)

    E Prabhakar Reddy


    Full Text Available Role of free radicals has been proposed in the pathogenesis of many diseases. Gastric cancer is a common disease worldwide, and leading cause of cancer death in India. Severe oxidative stress produces reactive oxygen species (ROS and induces uncontrolled lipid peroxidation. Albumin, uric acid (UA and Bilirubin are important physiological antioxidants. We aimed to evaluate and assess the role of oxidative stress (OS and physiological antioxidant system in stomach cancer patients. Lipid peroxidation measured as plasma Thio Barbituric Acid Reactive substances (TBARS, was found to be elevated significantly (p=0.001 in stomach cancer compared to controls along with a decrease in plasma physiological antioxidant system. The documented results were due to increased lipid peroxidation and involvement of physiological antioxidants in scavenging free radicals but not because of impaired hepatic and renal functions.

  7. Synthesis of new annulated pyrano[2,3-d]pyrimidine derivatives using organo catalyst (DABCO in aqueous media

    Directory of Open Access Journals (Sweden)

    Ajmal R. Bhat


    Full Text Available A selective method for the synthesis of annulated pyrano[2,3-d]pyrimidines has been developed. It was shown that base catalysis is more efficient in this reaction, rather than acid catalysis as it is believed that 1,4-diazabicyclo[2.2.2]octane (DABCO is N-type base catalyst used for the synthesis of pyrano[2,3-d]pyramidine derivatives via one-pot three component condensation reactions of various aromatic aldehydes, active methylene compounds and barbituric acid in aqueous ethanol carried at normal temperature. The potential application of DABCO in organic synthesis increasing rapidly because of its reaction simplicity, less pollution, and minimum reaction time, high yields of the biological active products, uses less toxic solvents and low cost chemicals.

  8. ZrOCl2.8H2O as a green and efficient catalyst for the expeditious synthesis of substituted 3-arylpyrimido[4,5-c]pyridazines in water

    Directory of Open Access Journals (Sweden)

    Mehdi Rimaz


    Full Text Available A new and simple synthetic methodology for the preparation of 3-arylpyrimido[4,5-c]pyridazine-5,7(6H,8H-diones and 3-aryl-5-oxo-7-thioxo-7,8-dihydropyrimido[4,5-c]pyridazin-5(6H-ones by a one-pot three component reaction of barbituric acid or thiobarbituric acid with arylglyoxals in the presence of catalytic amount of ZrOCl2∙8H2O as green Lewis acid and hydrazine hydrate at ambient temperature in water was reported. All of these pyrimidopyridazines derivatives have one clustered water molecule in their molecular structure. The use of ZrOCl2∙8H2O catalyst is feasible because of its easy availability, convenient handling, high stability, simple recovery, reusability, good activity and eco-friendly.

  9. Micellar solubilization in strongly interacting binary surfactant systems. [Binary surfactant systems of: dodecyltrimethylammonium chloride + sodium dodecyl sulfate; benzyldimethyltetradecylammonium chloride + tetradecyltrimethylammonium chloride

    Energy Technology Data Exchange (ETDEWEB)

    Treiner, C. (Universite Pierre et Marie Curie, Paris (France)); Nortz, M.; Vaution, C. (Faculte de Pharmacie de Paris-sud, Chatenay-Malabry (France))


    The apparent partition coefficient P of barbituric acids between micelles and water has been determined in mixed binary surfactant solutions from solubility measurements in the whole micellar composition range. The binary systems chosen ranged from the strongly interacting system dodecyltrimethylammonium chloride + sodium dodecyl sulfate to weakly interacting systems such as benzyldimethyltetradecylammonium chloride + tetradecyltrimethyammonium chloride. In all cases studied, mixed micelle formation is unfavorable to micellar solubilization. A correlation is found between the unlike surfactants interaction energy, as measured by the regular solution parameter {beta} and the solute partition coefficient change upon surfactant mixing. By use of literature data on micellar solubilization in binary surfactant solutions, it is shown that the change of P for solutes which are solubilized by surface adsorption is generally governed by the sign and amplitude of the interaction parameter {beta}.

  10. Comparison of Laboratory Experiments of Chemical, Biological, and Thermal Methods for Treatment of Chlorinated Solvent DNAPL at Kærgård Plantage in Denmark

    DEFF Research Database (Denmark)

    Christophersen, Mette; Christensen, Jørgen Fjeldsø; Jørgensen, Torben H.


    The Kærgård Plantage megasite on the western coast of Denmark represents one of the most difficult remediation challenges in Scandinavia. Disposal of an estimated 280,000 m3 of pharmaceutical wastes at the site from 1956 to 1973 resulted in the development of a complex mixture of contaminants...... in soil and groundwater, including sulfonamides, barbiturates, aniline, pyridine, chlorinated solvents (chloroethenes), fuel hydrocarbons, mercury, cyanide, lithium and many other compounds.  Wastes were disposed in six pits that continue to leach contaminants to groundwater. Contaminants in groundwater...... technologies for remediation of the residual wastes below the water table - first in the laboratory and then in pilot tests. Given the complex and highly concentrated mixture of contaminants, implementation of multiple or sequenced remediation technologies may be required to achieve cleanup goals.  An...

  11. Hair analysis in toxicological investigation of drug-facilitated crimes in Denmark over a 8-year period

    DEFF Research Database (Denmark)

    Wang, Xin; Johansen, Sys Stybe; Nielsen, Marie Katrine Klose


    -facilitated crimes (DFCs). This paper presents an overview of toxicological investigations that have used hair analysis in DFC cases from 2009 to 2016 in Denmark. Hair concentrations were determined for 24 DFC-related drugs and metabolites, including benzodiazepines and other hypnotics, antihistamines, opioid...... analgesics, antipsychotics, barbiturates, and illicit drugs from DFC cases. Drug detection in hair in DFC cases following a single or few intakes of chlorprothixene, codeine, diphenhydramine, oxazepam, oxycodone, promethazine, and phenobarbital is reported for the first time in forensic toxicology....... A literature review on concentrations in the published DFC-related hair cases and on concentrations in hair of these substances after single and multiple doses is included. These cases demonstrate the value of segmental hair analysis in DFCs and facilitate future interpretations of results....

  12. [Effect of psychotropic drugs on vigilance and motor performances]. (United States)

    Amado-Boccara, I; Galinowski, A; Poirier, M F; Lôo, H


    This review paper deals with the impact of psychotropic drugs on vigilance, awakening and motricity. Antidepressants can be divided into 3 categories, depending on the subject's awakening: sedatives with a strong anticholinergic component, compounds devoid of positive or negative impact on cognition and stimulating antidepressants. The principal effect of lithium is to lengthen the reaction time. Taken acutely, neuroleptics produce alterations of fine motor gestures, but when taken chronically they spare the functioning of cognition. Benzodiazepines act on vigilance in various ways, depending on their half-life and on their plasma peak time after oral administration. The effect of anticonvulsants on cognition is more pronounced with phenytoin and barbiturates than with carbamazepine or valproate sodium. The problems of comparative analysis in this field and the trends in current studies are underlined.

  13. [The development of the method for enzymatic hydrolysis for the extraction of toxic substances from the hair samples]. (United States)

    Slustovskaya, Yu V; Krys'ko, M V; Strelova, O Yu

    The objective of the present study was to develop and validate the method for the extraction of toxic substances from the hair samples as exemplified by enzymatic hydrolysis of barbituric acid derivatives. The experiments were carried out with the use of laboratory animals (white female rats and albino guinea pigs) that had been daily given a phenobarbital solution per os during 4 months preceding the study. The hairs obtained from the experimental animals were subjected to acid hydrolysis with a 6 mole hydrochloric acid and enzymatic hydrolysis with the use of chymopsin, trypsin, chymotrypsin, and papain solutions. The analysis of the extracted materials was performed by means of gas chromatography with mass-selective detection. The application of the proposed method for enzymatic hydrolysis produced the better results than acid hydrolysis. This technique was validated. The results of the study made possible the comparative characteristic of the effectiveness of acid and enzymatic hydrolysis.

  14. Hydrogen bonding in tight environments

    DEFF Research Database (Denmark)

    Pirrotta, Alessandro; Solomon, Gemma C.; Franco, Ignacio


    The single-molecule force spectroscopy of a prototypical class of hydrogen-bonded complexes is computationally investigated. The complexes consist of derivatives of a barbituric acid and a Hamilton receptor that can form up to six simultaneous hydrogen bonds. The force-extension (F-L) isotherms...... of the host-guest complexes are simulated using classical molecular dynamics and the MM3 force field, for which a refined set of hydrogen bond parameters was developed from MP2 ab initio computations. The F-L curves exhibit peaks that signal conformational changes during elongation, the most prominent...... of which is in the 60-180 pN range and corresponds to the force required to break the hydrogen bonds. These peaks in the F-L curves are shown to be sensitive to relatively small changes in the chemical structure of the host molecule. Thermodynamic insights into the supramolecular assembly were obtained...

  15. Validation of a method for the targeted analysis of 96 drugs in hair by UPLC-MS/MS

    DEFF Research Database (Denmark)

    Montesano, Camilla; Johansen, Sys Stybe; Nielsen, Marie Katrine Klose


    in drug facilitated assaults (DFA); however, chronic use (compliance) can also be examined. The method has been fully validated for the drugs included in the study. The accuracy of the method was demonstrated by the analysis of certified authentic hair samples containing common drugs of abuse. The hair......The method presented in this study allows the screening and quantification of 96 drugs, from different groups: opiates, amphetamines, hallucinogens, benzodiazepines, antihistamines, antidepressants, antipsychotics, barbiturates and other sedatives, muscle relaxants, etc. in hair. Drugs...... are extracted from 10mg of washed hair in 18h by a mixture of methanol:acetonitrile:ammonium formate (pH 5.3). Absolute recovery ranged from 70% to 106% for 75% of the analytes. The limits of detection in the low pg/mg range, may allow the detection of single dose drug exposure, with possible application...

  16. The ketogenic diet as broad-spectrum treatment for super-refractory pediatric status epilepticus: challenges in implementation in the pediatric and neonatal intensive care units. (United States)

    Cobo, Nicole H; Sankar, Raman; Murata, Kristina K; Sewak, Sarika L; Kezele, Michele A; Matsumoto, Joyce H


    Refractory status epilepticus carries significant morbidity and mortality. Recent reports have promoted the use of the ketogenic diet as an effective treatment for refractory status epilepticus. We describe our recent experience with instituting the ketogenic diet for 4 critically ill children in refractory status epilepticus, ranging in age from 9 weeks to 13.5 years after failure of traditional treatment. The ketogenic diet allowed these patients to be weaned off continuous infusions of anesthetics without recurrence of status epilepticus, though delayed ketosis and persistently elevated glucose measurements posed special challenges to effective initiation, and none experienced complete seizure cessation. The ease of sustaining myocardial function with fatty acid energy substrates compares favorably over the myocardial toxicity posed by anesthetic doses of barbiturates and contributes to the safety profile of the ketogenic diet. The ketogenic diet can be implemented successfully and safely for the treatment of refractory status epilepticus in pediatric patients. © The Author(s) 2014.

  17. [Pharmacological treatment of syndromes of aggressivity]. (United States)

    Itil, T M


    In the treatment of violent-aggressive behavior, four major groups of drugs emerged: 1. Major tranquilizers in the treatment of aggressive-violent behavior associated with psychotic syndromes. 2. Anti-epileptic drugs such as diphenylhydantoin and barbiturates in the treatment of aggressive-violent behavior within the epileptic syndrome. 3. Psychostimulants in the treatment of aggressive behavior of adolescents and children within behavior disturbances. 4. Anti-male hormones such as cyproterone acetate in the treatment of violent-aggressive behavior associated with pathological sexual hyperactivity. Whereas each category of drug is predominantly effective in one type of aggressive syndrome, it may also be effective in other conditions as well. Aggression as a result of a personality disorder is most difficult to treat with drugs.

  18. Treatment and outcome of the severely head injured child. (United States)

    Pfenninger, J; Kaiser, G; Lütschg, J; Sutter, M


    Twenty-four children (aged 3 months to 14 years) with severe head injuries were treated by means of invasive neurointensive care for normalizing intracranial pressure (ICP) involving hyperventilation, control of body temperature, dexamethasone, barbiturates and continuous intracranial and arterial pressure monitoring. The Glasgow Coma Scale before initiation of treatment was 3-4 in 8, 5-6 in 9 and 7 in 7 patients. Moderately to severely elevated ICP was observed in 20 patients. Seven developed acute and subacute space occupying intracranial hematomas. Nineteen children (79%) survived, most often with good recovery and 5 (21%) died. Severely elevated ICP, presence of severe consumption coagulopathy and loss of components in brain auditory evoked potentials were significantly more frequent in the fatal group. We conclude that the prognosis of the severely head injured child can be improved by prompt resuscitation and aggressive neurointensive care but probably not, however, to the extent postulated in recent literature.

  19. Sedative-hypnotic drug withdrawal syndrome: recognition and treatment [digest]. (United States)

    Santos, Cynthia; Olmedo, Ruben E; Kim, Jeremy


    Sedative-hypnotic drugs include gamma-Aminobutyric acid (GABA)ergic agents such as benzodiazepines, barbiturates, gamma-Hydroxybutyric acid [GHB], gamma-Butyrolactone [GBL], baclofen, and ethanol. Chronic use of these substances can cause tolerance, and abrupt cessation or a reduction in the quantity of the drug can precipitate a life-threatening withdrawal syndrome. Benzodiazepines, phenobarbital, propofol, and other GABA agonists or analogues can effectively control symptoms of withdrawal from GABAergic agents. Managing withdrawal symptoms requires a patient-specific approach that takes into account the physiologic pathways of the particular drugs used as well as the patient's age and comorbidities. Adjunctive therapies include alpha agonists, beta blockers, anticonvulsants, and antipsychotics. Newer pharmacological therapies offer promise in managing withdrawal symptoms. [Points & Pearls is a digest of Emergency Medicine Practice].

  20. Alterations in offspring behavior induced by chronic prenatal cocaine dosing. (United States)

    Smith, R F; Mattran, K M; Kurkjian, M F; Kurtz, S L


    Sperm-positive female Long-Evans hooded rats were dosed subcutaneously with 10 mg/kg/day cocaine or an equal volume of vehicle (0.9% sterile saline) from gestation day 4 (GD4) through GD18. Offspring were assessed for development of negative geotaxis, righting reflex, spontaneous alternation, and open field activity, and for adult behaviors including DRL-20 acquisition, water maze, visual discrimination, barbiturate sleep time, shuttlebox avoidance, footshock sensitivity, and tail flick latency. Cocaine dosing produced no significant effects on dam weight gain, any measure of litter size and weight, or early postnatal behavioral tests, but there were significant drug effects on development of spontaneous alternation, development of open field activity, DRL-20 acquisition, water maze performance, tail flick, and footshock sensitivity. These data suggest that chronic administration of a modest dose of cocaine during gestation in the rat alters a number of behaviors in the offspring.

  1. Primate study suggests pentobarbital may help protect the brain during radiation therapy

    International Nuclear Information System (INIS)

    Skolnick, A.


    Radiation therapy, an often indispensable treatment for a wide range of brain tumors, is a double-edged sword, especially when used to treat children. Research reported at the 72nd Annual Meeting of the Endocrine Society, in Atlanta, Ga., now suggests that pentobarbital and perhaps other barbiturates may help protect the brain from radiation-induced damage, especially to the pituitary and hypothalmus, where such damage can lead to serious, life-long problems for children. Jeffrey J. Olson, MD, now assistant professor of neurosurgery at Emory University School of Medicine, Atlanta, reported the results of a study of the radioprotective effects of pentobarbital on the brain of a primate, which he and colleagues at the National Institute of Neurological Disorders and Stroke recently completed

  2. Analysis of infantile subdural hematoma caused by abuse

    International Nuclear Information System (INIS)

    Park, Young-Soo; Nishio, Kenji; Fujimoto, Takatoshi; Nakase, Hiroyuki; Okuchi, Kazuo


    We report infantile subdural hematoma caused by abuse. Between January 2006 and December 2009, 10 cases of definite and highly suspicious abusive subdural hematoma in infants were treated at Nara Medical University Hospital. The mean age was 5.4 months. On CT examination, severe cerebral swelling was seen in 8 (80%) and wide spreading cerebral ischemia and atrophy in 9 (90%). Retinal hemorrhage was commonly seen in this series (90%). Subdural drainage and/or subdural-peritoneal shunt surgeries were performed in 6 cases, and intensive combined therapy of mild hypothermia and barbiturate was adapted in 7 cases. Favorable outcome was achieved in only 3 cases. In spite of aggressive treatment, clinical outcome are still bad. In our series, assailants were predominantly not father but mother. There were various and complex factors for child abuse. Cautious insight and suspicion are necessary to detect abusive injuries in infants. It is very important to endeavor to prevent recurrences of abusive injuries. (author)

  3. Inorganic-organic hybrid silica based tin complex as a novel, highly efficient and recyclable heterogeneous catalyst for the one-pot preparation of spirooxindoles in water. (United States)

    Ghahremanzadeh, Ramin; Rashid, Zahra; Zarnani, Amir-Hassan; Naeimi, Hossein


    In the present study, a tin complex immobilized on silica gel as a novel, green, highly efficient and heterogeneous reusable catalyst was synthesized by grafting 2-amino benzamide onto the silica gel surface as a result of the reaction between isatoic anhydride and 3-aminopropyl-functionalized silica gel, followed by complexing with tin chloride. The resulting organic-inorganic hybrid material was evaluated in the one-pot three-component synthesis of spiro[indoline-pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]trione derivatives in water via the condensation reaction of isatins, barbituric acids, and 1H-pyrazol-5-amines. All the reactions were completed in short reaction times and all the products were obtained in high to excellent yields with high purity. In addition, the synthesized novel catalyst could be separated from the reaction mixture by simple filtration and can be reused up to seven runs without significant loss in activity.

  4. Electrophysiologic studies of the thoracic limb of the horse. (United States)

    Blythe, L L; Kitchell, R L


    The cutaneous innervation of the thoracic limb was investigated in 18 barbiturate-anesthetized horses, using electrophysiologic techniques. The cutaneous area (CA) innervated by each cutaneous nerve was delineated in at least 4 horses by stroking the hairs with a small watercolor brush while recording from the nerve. Mapping of adjacent CA revealed areas of considerable overlap. The part of a CA of a given nerve supplied only by that nerve is referred to as its autonomous zone (AZ). In contrast to the standard textbook illustrations cutaneous branches of the axillary, radial, musculocutaneous, and ulnar nerves overlapped extensively in the antebrachium. Clinically testable AZ were found in the antebrachium for the caudal cutaneous antebrachial nerve of the ulnar nerve and in the carpus and manus for the cutaneous branches of the median, ulnar, and musculocutaneous nerves; AZ were not found for the cutaneous branches of the radial and axillary nerves.

  5. The use of extracorporeal life support in adolescent amlodipine overdose (United States)

    Persad, Elizabeth A.; Raman, Lakshmi; Thompson, Marita T.; Sheeran, Paul W.


    Calcium channel blocker (CCB) toxicity is associated with refractory hypotension and can be fatal. A 13 year old young woman presented to the emergency department(ED) six hours after an intentional overdose of amlodipine, barbiturates, and alcohol. She remained extremely hypotensive despite the administration of normal saline and calcium chloride and despite infusions of norepinephrine, epinephrine, insulin, and dextrose. Due to increasing evidence of end organ dysfunction, Extracorporeal Life Support (ECLS) was initiated 9 hours after presentation to the ED. The patient's blood pressure and end organ function immediately improved after cannulation. She was successfully decannulated after 57 hours of ECLS and was neurologically intact. Patients with calcium channel blocker overdose who are resistant to medical interventions may respond favorably to early ECLS. PMID:23559727

  6. Shelf Life Prediction for Canned Gudeg using Accelerated Shelf Life Testing (ASLT) Based on Arrhenius Method (United States)

    Nurhayati, R.; Rahayu NH, E.; Susanto, A.; Khasanah, Y.


    Gudeg is traditional food from Yogyakarta. It is consist of jackfruit, chicken, egg and coconut milk. Gudeg generally have a short shelf life. Canning or commercial sterilization is one way to extend the shelf life of gudeg. This aims of this research is to predict the shelf life of Andrawinaloka canned gudeg with Accelerated Shelf Life Test methods, Arrhenius model. Canned gudeg stored at three different temperature, there are 37, 50 and 60°C for two months. Measuring the number of Thio Barbituric Acid (TBA), as a critical aspect, were tested every 7 days. Arrhenius model approach is done with the equation order 0 and order 1. The analysis showed that the equation of order 0 can be used as an approach to estimating the shelf life of canned gudeg. The storage of Andrawinaloka canned gudeg at 30°C is predicted untill 21 months and 24 months for 25°C.

  7. Methotrexate for psoriasis: 1981. (United States)

    Rees, R B


    Although not stated in body of this article, it is best to start treatment with a very small test dose. Furthermore, one should use methotrexate only when other methods fail or are impractical. In general, the criterion of life-ruining disease should be considered the primary indication. Drugs interactions should be avoided. Probenecid, phenylbutazone, and colchicine are contraindicated. Increased toxicity may occur with concomitant use of salicylates, sulfonamides, barbiturates, para-aminobenzoic acid, diphenylhydantoin, oral contraceptives, and weak organic acids. It would appear at this time that any dose being administered more often than once weekly is too toxic for the liver. Perhaps the intramuscular route is safest. Finally, the official guidelines should be followed as closely as possible, even possibly including liver biopsies. It should be recognized that liver biopsy is not without hazard, as deaths have been reported from simple needle liver biopsies.

  8. [Suicidal poisoning with benzodiazepines]. (United States)

    Chodorowski, Z; Sein Anand, J


    In the period from 1987 to 1996, 103 patients with suicidal benzodiazepines poisoning were treated, including 62 women and 41 men from 16 to 79 (mean 34) years old. 23 persons were poisoned only by benzodiazepines, in 80 remaining cases intoxications were mixed eg. including benzodiazepines and alcohol, tricyclic antidepressants, barbiturates, opioids, phenothiazines. The main causes of suicides were mainly depression, drug addiction and alcoholism. Nobody died in the benzodiazepines group, while mortality rate in the group of mixed poisoning was 4%. Prescribing benzodiazepines by physicians was quite often not justified and facilitated, among others, accumulation of the dose sufficient for suicide attempt. Flumazenil was efficient for leading out from coma in 86% of cases with poisoning only by benzodiazepines and 13% of cases with mixed intoxications mainly containing benzodiazepines and alcohol or carbamazepine.

  9. Pentobarbital inhibits glucose uptake, but not water transport by glucose transporter type 3. (United States)

    Tomioka, Shigemasa; Kaneko, Miyuki; Nakajo, Nobuyoshi


    To understand the mechanisms underlying the neuroprotective efficacy of barbiturates, the effect of pentobarbital on glucose uptake and water transport was determined in Xenopus oocytes expressing glucose transporter type 3 (GLUT3). Pentobarbital induced a 50% concentration-dependent inhibition in glucose uptake, but exerted no effect on water transport by GLUT3. Eadie-Hofstee analysis showed that pentobarbital decreased Vmax significantly, but not Km of GLUT3 for 2-deoxy-D-glucose. Although the protein kinase C (PKC) activator significantly decreased glucose uptake by GLUT3, no additive or synergistic interactions were observed between the PKC activator and pentobarbital. Our results suggest that pentobarbital may play an important role in neuroprotection by inhibition of glucose uptake by GLUT3 by a mechanism involving PKC.

  10. Intestinal microbiota regulate xenobiotic metabolism in the liver.

    Directory of Open Access Journals (Sweden)

    Britta Björkholm

    Full Text Available BACKGROUND: The liver is the central organ for xenobiotic metabolism (XM and is regulated by nuclear receptors such as CAR and PXR, which control the metabolism of drugs. Here we report that gut microbiota influences liver gene expression and alters xenobiotic metabolism in animals exposed to barbiturates. PRINCIPAL FINDINGS: By comparing hepatic gene expression on microarrays from germfree (GF and conventionally-raised mice (SPF, we identified a cluster of 112 differentially expressed target genes predominantly connected to xenobiotic metabolism and pathways inhibiting RXR function. These findings were functionally validated by exposing GF and SPF mice to pentobarbital which confirmed that xenobiotic metabolism in GF mice is significantly more efficient (shorter time of anesthesia when compared to the SPF group. CONCLUSION: Our data demonstrate that gut microbiota modulates hepatic gene expression and function by altering its xenobiotic response to drugs without direct contact with the liver.

  11. Nuclear-medicine progress report for quarter ending March 31, 1982

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, F.F. Jr.; Ambrose, K.R.; Butler, T.A.; Goodman, M.M.; Hoeschele, J.D.; Srivastava, P.C.


    The synthesis of a radioiodinated vinyl barbituric acid analog as a potential cerebral perfusion agent is reported. The /sup 125/I-labeled barbiturate will be evaluated in rats. In order to evaluate the myocardial uptake and retention of methyl-branched fatty acids, racemic 14-(p-(/sup 125/I)iodophenyl)-2-(R,S)-methyl-tetradecanoic acid and 15-(p-(/sup 125/I)iodophenyl)-3-(R,S)-methyl-pentadecanoic acid were prepared by a new route in which methyl branching was introduced by a unique oxazoline intermediate. The branched fatty acids were evaluated in rats and showed good heart uptake, but blood levels were high. Future studies will be directed at resolution of the isomers and evaluation of the R- and S-agents in rats. Eight shipments of /sup 191/Os-potassium osmate were made to Medical Cooperative investigators for preparation of the /sup 191/Os-/sup 191m/Ir generator to carry out radionuclide angiography with /sup 191m/Ir, and several shipments of /sup 195m/Pt-labeled cis-dichlorodiammineplatinum-(II) (cis-DDP) were supplied to collaborators for evaluation of its antitumor and pharmacologic properties. A variety of structurally modified /sup 125/I- and /sup 123m/Te-labeled fatty acid analogs developed in the Nuclear Medicine program were supplied to the Massachusetts General Hospital for further evaluation, including imaging studies and measurement of the myocardial extraction properties in dogs, and tin-117m was supplied to collaborators for preparation of several agents for evaluation of its potential therapeutic use for bone disease. (ERB)

  12. Association between psychotropic medications and presence of sleep bruxism: a systematic review. (United States)

    Melo, Gilberto; Dutra, Kamile Leonardi; Rodrigues Filho, Rubens; de Oliveira Lira Ortega, Adriana; Porporatti, André Luís; Dick, Bruce; Flores-Mir, Carlos; De Luca Canto, Graziela


    The purpose of this study was to systematically review the literature for studies that investigated the association between use of psychotropic medications and presence of sleep bruxism (SB). Observational studies were selected in a two-phase process. Searches were performed on six electronic databases and a grey literature search was conducted on three databases. SB diagnosis was based on questionnaires or clinical examinations; no polysomnography exams were performed. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies. Overall quality of evidence was evaluated according to the Grading of Recommendations Assessment, Development and Evaluation criteria. Five analytical cross-sectional studies were included, evaluating antidepressants, anticonvulsants, and psychostimulants. One study was judged as low risk of bias, three as moderate risk, and one high risk. Antidepressants were evaluated in adult populations only; duloxetine (Odds Ratio [OR]=2.16; 95% Confidence Interval [95%CI]=1.12-4.17), paroxetine (OR=3.63; 95%CI=2.15-6.13) and venlafaxine (OR=2.28; 95%CI=1.34-3.86) were positively associated with SB risk. No increased odds of SB were observed considering use of citalopram, escitalopram, fluoxetine, mirtazapine, and sertraline. With regard to anticonvulsants, only barbiturates were associated with SB in children (OR=14.70; 95%CI =1.85-116.90), while no increased odds were observed for benzodiazepine, carbamazepine, and valproate. The only psychostimulant evaluated was methylphenidate and an association with SB was observed in adolescents (OR=1.67; 95%CI=1.03-2.68). Findings from this SR suggested that medications such as duloxetine, paroxetine, venlafaxine, barbiturates, and methylphenidate might be associated with SB; however, overall quality of evidence was considered very low and, therefore, caution is recommended. This article is protected by copyright. All rights reserved. This

  13. The determination of total cyanide in solutions containing uranium and gold

    International Nuclear Information System (INIS)

    Solomons, M.; Dixon, K.


    This report gives the results of a limited investigation of three distillation procedures and their variants for the separation of cyanide. The spectrophotometric measurement, which follows the distillation, uses either a mixture of pyridine and pyrazolone, or a mixture of pyridine and barbituric acid. It was found that the method published in the South Africa Government Gazette in 1969 gives quantitative recoveries from potassium cyanide solutions but not in the presence of gold. The ligand-displacement method did not give quantitative recoveries in the presence of gold, except when zinc was added to the distilland, and it then failed to give a quantitative recovery of cyanide from ferrocyanide. These two methods were therefore rejected as unsuitable for the determination of cyanide in solutions containing small amounts of uranium and gold. The procedure of the American Public Health Association (APHA) was found to give quantitative recoveries in the presence of gold, uranium, thiocyanate, and ferrocyanide when cuprous chloride, or cuprous chloride with magnesium chloride, are added to the distilland. The spectrophotometric measurement using a mixture of pyridine and barbituric acid is preferred. The calibration range of the method is 0,5 to 6μg of cyanide, and the limit of determination is 0,04μg/cm 3 . (The relative standard deviation of the method is 0,05.) The distillation time in the APHA method is approximately two and a half hours; with 3 distillation trains, up to 9 distillations can be made per day, plus a further 2 hours for the spectrophotometric determination. The preferred laboratory method is detailed in an appendix

  14. Response of rat brain protein synthesis to ethanol and sodium barbital

    International Nuclear Information System (INIS)

    Tewari, S.; Greenberg, S.A.; Do, K.; Grey, P.A.


    Central nervous system (CNS) depressants such as ethanol and barbiturates under acute or chronic conditions can induce changes in rat brain protein synthesis. While these data demonstrate the individual effects of drugs on protein synthesis, the response of brain protein synthesis to alcohol-drug interactions is not known. The goal of the present study was to determine the individual and combined effects of ethanol and sodium barbital on brain protein synthesis and gain an understanding of the mechanisms by which these alterations in protein synthesis are produced. Specifically, the in vivo and in vitro effects of sodium barbital (one class of barbiturates which is not metabolized by the hepatic tissue) were examined on brain protein synthesis in rats made physically dependent upon ethanol. Using cell free brain polysomal systems isolated from Control, Ethanol and 24 h Ethanol Withdrawn rats, data show that sodium barbital, when intubated intragastrically, inhibited the time dependent incorporation of 14 C) leucine into protein by all three groups of ribosomes. Under these conditions, the Ethanol Withdrawn group displayed the largest inhibition of the 14 C) leucine incorporation into protein when compared to the Control and Ethanol groups. In addition, sodium barbital when added at various concentrations in vitro to the incubation medium inhibited the incorporation of 14 C) leucine into protein by Control and Ethanol polysomes. The inhibitory effects were also obtained following preincubation of ribosomes in the presence of barbital but not cycloheximide. Data suggest that brain protein synthesis, specifically brain polysomes, through interaction with ethanol or barbital are involved in the functional development of tolerance. These interactions may occur through proteins or polypeptide chains or alterations in messenger RNA components associated with the ribosomal units

  15. Rates and Correlates of Binge Drinking Among College Students With Disabilities, United States, 2013. (United States)

    West, Steven L; Graham, Carolyn W; Temple, Peter

    Our objective was to provide the first comprehensive picture of alcohol use and binge drinking by US college students with disabilities (SWDs), who represent at least 11% (1.6 million) of the US college student population. In fall 2013, we used a stratified random sampling technique to identify and recruit 2440 SWDs from 122 US colleges and universities. A total of 1285 (53%) SWDs from 61 (50%) colleges and universities completed a survey of alcohol and other drug use and the use of substances by student peers. We conducted 4 multiple logistic regression analyses to compare binge-drinking and non-binge-drinking SWDs by potential correlates of such use and a final model that included only significant variables. SWDs aged confidence interval [CI], 0.82-0.99) who spent more time vs less time socializing (OR = 1.24; 95% CI, 1.11-1.38), who spent less time vs more time studying (OR = -0.89; 95% CI, -0.80 to -0.99), and who used vs did not use marijuana (OR = 1.44; 95% CI, 1.18-1.75) or amphetamines (OR = 1.82; 95% CI, 1.15-2.89) were significantly more likely to binge drink. SWDs who reported using barbiturates were less likely to binge drink than were those who did not use barbiturates (OR = -0.36; 95% CI, -0.21 to -0.61). In the final model, use of amphetamines (OR = 1.74; 95% CI, 1.15-2.65) or marijuana (OR = 1.60; 95% CI, 1.32-1.94) was the highest predictor of binge drinking. SWDs' reported rates of binge drinking, although high, were not as high as those of nondisabled college students. Nevertheless, prevention efforts should be targeted toward college SWDs.

  16. [Gabaergic hypothesis of epilepsy and clinical experience: controversial actions of the new generation gabamimetic antiepileptic drugs]. (United States)

    Chmielewska, B


    Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in CNS can elevate level of neuronal excitability by the mechanisms of hyperpolarization. Gabaergic hypothesis of epileptogenesis influenced development of a group of gabamimetic antiepileptic drugs (AEDs). Powerful conventional AEDs barbiturates and benzodiazepines can directly activate GABA-A receptor but their usefulness is limited by development of dependence and tolerance to antiseizure activity. The second generation AEDs have been achieved by a rationale synthesis of compounds that could mimic or augment the activity of endogenous GABA. Vigabatrin (VGB) irreversibly inhibits GABA-T activity, tiagabine (TGB) inhibits GABA-reuptake system (GAT-1) and gabapentin (GPT) enhances GABA turnover in CNS. New drugs with selective and specific influence on GABA neurotransmission are non-toxic and well-tolerated, but some side-effects (aggravation of seizures, visual field deficit and psychotic reactions) seems to be strictly connected with their pharmacodynamic properties. Absence and probably myoclonic seizures noted in about 10% of patients under VGB seems to be the result of disturbed GABA inhibition in thalamic interneurons and non-controlled hyperactivity of excitatory neocortex-thalamus-neocotrex circuits. Perimetric examination might reveal peripheral, persistent binasal visual field deficit in about 30% of patients treated with VGB. This is probably the effect of cytotoxic influence of enormous accumulation of GABA in retinal neurons. Barbiturates and benzodiazepines can exacerbate intellectual functioning and behaviour. Some emotional and reactive disturbances are more characteristic for newer drugs. Serious depressive reactions and psychoses were observed respectively in 12.5 and 2.5% epileptics under VGB and anecdotically after TGB or GPT therapy. Newer selective and specific gabamimetic AEDs play an essential role as add-on therapy of pharmaco-resistant epilepsy, but they did not bring

  17. A Comparison of Pharmacologic Therapeutic Agents Used for the Reduction of Intracranial Pressure After Traumatic Brain Injury. (United States)

    Alnemari, Ahmed M; Krafcik, Brianna M; Mansour, Tarek R; Gaudin, Daniel


    In neurotrauma care, a better understanding of treatments after traumatic brain injury (TBI) has led to a significant decrease in morbidity and mortality in this population. TBI represents a significant medical problem, and complications after TBI are associated with the initial injury and postevent intracranial processes such as increased intracranial pressure and brain edema. Consequently, appropriate therapeutic interventions are required to reduce brain tissue damage and improve cerebral perfusion. We present a contemporary review of literature on the use of pharmacologic therapies to reduce intracranial pressure after TBI and a comparison of their efficacy. This review was conducted by PubMed query. Only studies discussing pharmacologic management of patients after TBI were included. This review includes prospective and retrospective studies and includes randomized controlled trials as well as cohort, case-control, observational, and database studies. Systematic literature reviews, meta-analyses, and studies that considered conditions other than TBI or pediatric populations were not included. Review of the literature describing the current pharmacologic treatment for intracranial hypertension after TBI most often discussed the use of hyperosmolar agents such as hypertonic saline and mannitol, sedatives such as fentanyl and propofol, benzodiazepines, and barbiturates. Hypertonic saline is associated with faster resolution of intracranial hypertension and restoration of optimal cerebral hemodynamics, although these advantages did not translate into long-term benefits in morbidity or mortality. In patients refractory to treatment with hyperosmolar therapy, induction of a barbiturate coma can reduce intracranial pressure, although requires close monitoring to prevent adverse events. Current research suggests that the use of hypertonic saline after TBI is the best option for immediate decrease in intracranial pressure. A better understanding of the efficacy of

  18. Repeated administration of an aqueous spray-dried extract of the leaves of Passiflora alata Curtis (Passifloraceae) inhibits body weight gain without altering mice behavior. (United States)

    Braga, Andressa; Stein, Ana Cristina; Dischkaln Stolz, Eveline; Dallegrave, Eliane; Buffon, Andréia; do Rego, Jean-Claude; Gosmann, Grace; Fialho Viana, Alice; Kuze Rates, Stela Maris


    Passiflora alata is a Southern American species that constitutes many traditional remedies as well as phytomedicines used for sedative and anxiolytic purposes in Brazil. However studies on repeated treatment effects are scarce. To evaluate behavioral, physiological and biochemical effects of the repeated treatment with an aqueous spray-dried extract of Passiflora alata leaves containing 2.5% (w/v) of flavonoids (PA) in mice. Male adult CF1 mice were treated (p.o.) for 14 days with PA (2.5; 25 or 250 mg/kg). The feeding behavior was evaluated at the beginning (1h after the first administration) and at the end of the treatment (15th day). The body weight gain and food consumption were monitored along the days. On day 15 mice were evaluated on plus maze, spontaneous locomotor activity, catalepsy and barbiturate sleeping time tests. Serum glucose, lipids, ALT and AST enzymes were determined. Liver, kidney, perirenal fat, epididymal and peritoneal fat were analyzed. The repeated treatment with the highest dose tested (250 mg/kg) did not alter the mice behavior on open field, elevated plus maze, catalepsy and barbiturate sleeping time tests. Repeated administration of PA 250 decreased mice feeding behavior and weight gain. PA 25 and PA 250 reduced mice relative liver weight and caused mild hepatic hydropic degeneration as well as a decrease in alanine aminotransferase (ALT) serum level. These results indicate that Passiflora alata does not present central cumulative effects and point to the needs of further studies searching for its hepatotoxicity as well as potential anorexigenic. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  19. Nuclear medicine technology progress report for quarter ending September 30, 1980

    International Nuclear Information System (INIS)

    Knapp, F.F. Jr.


    Brain uptake of several 75 Se- and /sup 123m/Te-labelled barbiturates is being studied. These new agents, substituted at the C-5 position, freely pass through the intact blood-brain barrier. Barbiturates labelled with gamma-emitting radionuclides may be an attractive new class of agents for measurement of regional cerebral blood flow. The diffusion chamber assay system has been used to assess the chronic effects of As 2 O 3 toxicity. A small osmotically actuated minipump was used to deliver aqueous As 2 O 3 at a continuous delivery rate to animals having intraperitoneally implanted diffusion chambers containing human lung cells (Flow 200). In these preliminary studies, a 49 to 53% inhibition of cell growth was observed over a five-day period when animals received As 2 O 3 at a dose of 1.7 to 2 mg (kg-d). These initial studies suggest that the minipump may be a useful means of studying the chronic effects of substances on cell proliferation in conjunction with the diffusion chamber assay system. A microscale synthesis of gold antirheumatoid agents was developed. This method involves reaction of thiohexose derivatives such as thioglucosetetraacetate (β-D-TGTA) with trialkylphosphinegold halide intermediates (R 3 PAu-Cl) in the presence of pyridine to give the coupling products R 3 PAu(β-D-TGTA) in good yield (>75%). Using this method, the triethyl analog Et 3 PAu(β-D-TGTA) and triphenyl analog [phi 3 PAu(β-D-TGTA)] have been prepared and characterized.This method will be used to prepare the 195 Au-labeled agents. The platinum antitumor agent cis-dichloro-trans-dihydroxy-bis-(isopropylamine)-platinum (IV) (CHIP) has been purified. This system is efficient for separation of CHIP from impurities produced during the synthetic sequence and will be used to prepare /sup 195m/Pt-CHIP for biological evaluation

  20. The psychological wellbeing of Iranian journalists: a descriptive study. (United States)

    Feinstein, Anthony; Feinstein, Saul; Behari, Maziar; Pavisian, Bennis


    Iran ranks 173 out of 180 countries on an index of press freedom. The purpose of the study was to assess the psychological wellbeing of Iranian journalists and document the stressors encountered in their work. A secure website was established and participants were given their unique identifying number and password to access the site. Newsrooms in Iran and the diaspora. Responses were received from 114 journalists (76%) of whom 65.8% were living in the diaspora. The mean age was 37.8 years (SD = 7.30) and 57% male. Type of stressor and behavioural data: Impact of Event Scale-revised for posttraumatic stress disorder, Beck Depression Inventory-II for depression. Stressors include arrest (41.2%), torture (19.3%), assault (10.5%), intimidation (51.4%) and family threatened (43.1%). Eighty nine (78.1%) journalists had stopped working on a story because of intimidation. Arrest, torture, intimidation and family threatened were associated with more intrusive and arousal PTSD symptoms (p < .01 to .001) and assault and intimidation with more depressive symptoms (p < .05). Almost a third of Iranian journalists regularly used barbiturates, with use correlating with symptoms of intrusion (p < .0001), avoidance (p < .01), arousal (p < .0001) and depression (p < .0001). 46.5% of Iranian journalists were not receiving therapy for their distress. The findings, the first of their kind, provide data highlighting the extraordinary degree of danger confronted by Iranian journalists, their emotional distress in response to this and their proclivity to self-medicate with barbiturates.

  1. Gamma-aminobutyric acid (GABA) and pentobarbital induce different conformational rearrangements in the GABA A receptor alpha1 and beta2 pre-M1 regions. (United States)

    Mercado, Jose; Czajkowski, Cynthia


    Gamma-aminobutyric acid (GABA) binding to GABA(A) receptors (GABA(A)Rs) triggers conformational movements in the alpha(1) and beta(2) pre-M1 regions that are associated with channel gating. At high concentrations, the barbiturate pentobarbital opens GABA(A)R channels with similar conductances as GABA, suggesting that their open state structures are alike. Little, however, is known about the structural rearrangements induced by barbiturates. Here, we examined whether pentobarbital activation triggers movements in the GABA(A)R pre-M1 regions. Alpha(1)beta(2) GABA(A)Rs containing cysteine substitutions in the pre-M1 alpha(1) (K219C, K221C) and beta(2) (K213C, K215C) subunits were expressed in Xenopus oocytes and analyzed using two-electrode voltage clamp. The cysteine substitutions had little to no effect on GABA and pentobarbital EC(50) values. Tethering chemically diverse thiol-reactive methanethiosulfonate reagents onto alpha(1)K219C and alpha(1)K221C affected GABA- and pentobarbital-activated currents differently, suggesting that the pre-M1 structural elements important for GABA and pentobarbital current activation are distinct. Moreover, pentobarbital altered the rates of cysteine modification by methanethiosulfonate reagents differently than GABA. For alpha(1)K221Cbeta(2) receptors, pentobarbital decreased the rate of cysteine modification whereas GABA had no effect. For alpha(1)beta(2)K215C receptors, pentobarbital had no effect whereas GABA increased the modification rate. The competitive GABA antagonist SR-95531 and a low, non-activating concentration of pentobarbital did not alter their modification rates, suggesting that the GABA- and pentobarbital-mediated changes in rates reflect gating movements. Overall, the data indicate that the pre-M1 region is involved in both GABA- and pentobarbital-mediated gating transitions. Pentobarbital, however, triggers different movements in this region than GABA, suggesting their activation mechanisms differ.

  2. Long-lasting effects of neonatal pentobarbital administration on spatial learning and hippocampal synaptic plasticity. (United States)

    Tachibana, Kaori; Hashimoto, Toshikazu; Kato, Rui; Tsuruga, Kenkichi; Ito, Ryoko; Morimoto, Yuji


    Exposure of newborn rats to antiepileptics such as barbiturates has long-lasting detrimental effects on the hippocampus and hippocampus-dependent behavior. However, the long-term consequences of neonatal administration with barbiturates on the hippocampal synaptic plasticity remain unresolved. In this study, we investigated the long-lasting effects of a neonatal administration of pentobarbital on spatial memory, paired-pulse plasticity in the population spikes, and long-term potentiation (LTP) in the hippocampal CA1 region of rats in vivo. Eight weeks after administration of pentobarbital (10 or 20mg/kg) on the seventh postnatal day (P7), rats showed impaired induction in LTP. During paired-pulse stimulation, pentobarbital-treated rats exhibited a greater facilitation of the test pulse population spike, suggesting a disruption in the inhibitory GABAergic synaptic transmission. Spatial learning in hidden platform task of the Morris water maze was impaired in pentobarbital-treated rats. Our present findings indicate that neonatal treatment with pentobarbital causes alterations in function of the hippocampal inhibitory synaptic transmission that persist into adulthood, likely contributing to the long-lasting abnormalities in the hippocampal LTP as well as learning ability. We also demonstrated significant respiratory disturbances, i.e., severe hypoxia, hypercapnia, and extracellular acidosis, in rats treated with pentobarbital on P7. Given that extracellular acidosis can also modulate synaptic transmission in the developing hippocampus, this finding led us to speculate regarding the influence of respiratory disturbances in pentobarbital-induced long-lasting hippocampal dysfunctions. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Activation of α6-containing GABAA receptors by pentobarbital occurs through a different mechanism than activation by GABA (United States)

    Fisher, Matthew T.; Fisher, Janet L.


    The GABAA receptors are ligand-gated chloride channels which are the targets for many clinically used sedatives, including the barbiturates. The barbiturate pentobarbital acts through multiple sites on the GABAA receptor. At low concentrations (μM), it acts as a positive allosteric modulator while at higher concentrations it can directly activate the receptor. This agonist action is influenced by the subunit composition of the receptor, and pentobarbital is a more effective agonist than GABA only at receptors containing an α6 subunit. The conformational change that translates GABA binding into channel opening is known to involve a lysine residue located in an extracellular domain between the 2nd and 3rd transmembrane domains. Mutations of this residue disrupt activation of the channel by GABA and have been linked to inherited epilepsy. Pentobarbital binds to the receptor at a different agonist site than GABA, but could use a common signal transduction mechanism to gate the channel. To address this question, we compared the effect of a mutating the homologous lysine residue in the α1 or α6 subunits (K278 or K277, respectively) to methionine on direct activation of recombinant GABAA receptors by GABA or pentobarbital. We found that this mutation reduced GABA sensitivity for both α1 and α6 subunits, but affected pentobarbital sensitivity only for the α1 subunit. This suggests that pentobarbital acts through a distinct signal transduction pathway at the α6 subunit, which may account for its greater efficacy compared to GABA at receptors containing this subunit. PMID:20109529

  4. Activation of alpha6-containing GABAA receptors by pentobarbital occurs through a different mechanism than activation by GABA. (United States)

    Fisher, Matthew T; Fisher, Janet L


    The GABA(A) receptors are ligand-gated chloride channels which are the targets for many clinically used sedatives, including the barbiturates. The barbiturate pentobarbital acts through multiple sites on the GABA(A) receptor. At low concentrations (muM), it acts as a positive allosteric modulator while at higher concentrations it can directly activate the receptor. This agonist action is influenced by the subunit composition of the receptor, and pentobarbital is a more effective agonist than GABA only at receptors containing an alpha6 subunit. The conformational change that translates GABA binding into channel opening is known to involve a lysine residue located in an extracellular domain between the 2nd and 3rd transmembrane domains. Mutations of this residue disrupt activation of the channel by GABA and have been linked to inherited epilepsy. Pentobarbital binds to the receptor at a different agonist site than GABA, but could use a common signal transduction mechanism to gate the channel. To address this question, we compared the effect of a mutating the homologous lysine residue in the alpha1 or alpha6 subunits (K278 or K277, respectively) to methionine on direct activation of recombinant GABA(A) receptors by GABA or pentobarbital. We found that this mutation reduced GABA sensitivity for both alpha1 and alpha6 subunits, but affected pentobarbital sensitivity only for the alpha1 subunit. This suggests that pentobarbital acts through a distinct signal transduction pathway at the alpha6 subunit, which may account for its greater efficacy compared to GABA at receptors containing this subunit.

  5. Adding Additional Acute Medications to a Triptan Regimen for Migraine and Observed Changes in Headache-Related Disability: Results From the American Migraine Prevalence and Prevention (AMPP) Study. (United States)

    Buse, Dawn C; Serrano, Daniel; Reed, Michael L; Kori, Shashi H; Cunanan, Cedric M; Adams, Aubrey Manack; Lipton, Richard B


    Though triptans are the most widely used acute treatments for migraine, response to treatment is sometimes suboptimal. Triptan therapy is often augmented by the addition of other acute treatments. The benefits of this practice have not been examined in large-scale, real-world observational studies. To assess changes in headache-related disability associated with adding additional acute treatments to a triptan regimen by category of added treatment including: a second triptan, nonsteroidal anti-inflammatory drugs (NSAID), opioids or barbiturates. Subjects were participants in the American Migraine Prevalence and Prevention study, a longitudinal, US population-based study of individuals with "severe" headache. Respondents who met International Classification of Headache Disorders 3 beta criteria for migraine were on triptan therapy per respondent self-report, used the same triptan, and provided headache-related disability data for at least 2 consecutive years. Subjects were divided based on headache days per month into 3 groups: low-frequency episodic migraine (LFEM, 0-4), moderate-frequency episodic migraine (MFEM, 5-9), and high-frequency episodic migraine/chronic migraine (HFEM/CM, ≥ 10 headache days per month). HFEM and CM were combined into a single group for analyses because of sample size limitations. Patterns of acute treatment for migraine were monitored from one year to the next over the following couplets of years (2005-2006, 2006-2007, 2007-2008, and 2008-2009). The first eligible couplet was analyzed for each respondent. Medication regimens studied included: (1) maintaining current triptan use (consistent group); (2) adding a different triptan; (3) adding an NSAID; or (4) adding a combination analgesic containing opioids or barbiturates. We assessed change in Migraine Disability Assessment (MIDAS) score from the first to the second year of a couplet, contrasting scores of participants with consistent use with those who added an acute treatment to

  6. Transcriptional regulation of the genes encoding cytochromes P450BM-1 and P450BM-3 in Bacillus megaterium by the binding of Bm3R1 repressor to Barbie box elements and operator sites. (United States)

    Liang, Q; Fulco, A J


    We previously reported (Liang, Q., He, J.-S., and Fulco, A.J. (1995) J. Biol. Chem. 270, 4438-4450) that Bm3R1, a repressor regulating the expression of P450BM-3 in Bacillus megaterium, could bind to Barbie box sequences in the 5'-flanking regions of barbiturate-inducible genes. We've now shown that pentobarbital does not inhibit in vitro binding of Bm3R1 to the P450BM-3 and P450BM-1 Barbie boxes (BB3 and BB1), although the palindromic operator sequence (OIII) of P450BM-3 did have a strong competitive effect on such binding. G39E-Bm3R1, a mutant of Bm3R1, did not bind to either Barbie box. In the presence of Bm3R1, portions of the regulatory regions of P450BM-3 and P450BM-1 were protected from DNase I digestion. These included 11 of the 15 base pairs of BB3 plus 7 base pairs 3' to BB3, BB1 plus 16 base pairs 3' to BB1, and, in the 5'-flanking region of P450BM-1, segments covering most of two palindromic sequences (OII and OIII) of 24 and 52 base pairs. These DNase I-protected regions (including OIII) showed considerable sequence identity, especially in a conserved poly(A) motif. Barbiturates did not inhibit binding of Bm3R1 to OI. OII in vitro while G39E-Bm3R1 did not bind. The regulatory effects of Bm3R1 on P450BM-1 and P450BM-3 were also evaluated in vivo using heterologous chloramphenicol acetyltransferase constructs and Western blotting. In the G39E mutant strain, both P450BM-1 and P450BM-3 were constitutively expressed, and the regulatory proteins Bm1P1 and Bm3P1, although still pentobarbital-inducible, had significantly higher basal levels of synthesis. In toto, our results show that Bm3R1 represses both P450BM-1 and P450BM-3 expression and that it may effect this by coordinate binding to operator and Barbie box sequences to produce looping of the P450BM-1 and P450BM-3 regulatory regions through protein-protein interaction.

  7. Uso não-médico de medicamentos psicoativos entre escolares do ensino fundamental e médio no Sul do Brasil Non-medical use of psychoactive medicines among elementary and high school students in Southern Brazil

    Directory of Open Access Journals (Sweden)

    Tatiane da Silva Dal Pizzol


    Full Text Available O objetivo do presente estudo é investigar a prevalência de uso não-médico de medicamentos entre escolares da rede de ensino público e privado de Passo Fundo, Rio Grande do Sul, Brasil, e sua distribuição em relação a fatores sócio-demográficos. Por meio de um delineamento transversal, foi aplicado um questionário de autopreenchimento a 5.057 estudantes a partir da quinta série do ensino fundamental até o terceiro ano do ensino médio. O questionário continha perguntas sobre o uso, sem receita médica, de anfetamínicos, ansiolíticos, barbitúricos, anticolinérgicos, opiáceos, orexígenos e anabolizantes. Da amostra, 7,7% consumiram ansiolíticos alguma vez na vida, 6,4% consumiram anfetamínicos, 2,2%, anabolizantes, e 1,1%, barbitúricos. Estudantes do sexo feminino apresentaram maior consumo de ansiolíticos e anfetamínicos, enquanto que o consumo de anabolizantes foi maior no sexo masculino. O padrão de consumo de medicamentos psicoativos é semelhante ao observado em adultos, sugerindo a necessidade de inclusão de crianças e adolescentes nas campanhas educativas para prevenção do uso indevido de medicamentos.The objective of this study is to assess the prevalence of and risk factors for the non-medical use of psychoactive medicines among students at public and private schools of Passo Fundo, Southern Brazil. A cross-sectional study was carried out using a questionnaire administered to 5,057 students from the 5th grade of elementary school to the 3rd year of high school. The questionnaire contained questions about the use of amphetamines, tranquilizers, barbiturates, anticholinergics, opioids, appetite stimulants, and anabolic steroids. Of the sample total, 7.7% had consumed tranquilizers sometime during their lives, 6.4% had used amphetamines, 2.2% had used anabolic steroids, and 1.1% had used barbiturates. Female students reported significantly greater consumption of tranquilizers and amphetamines, while anabolic

  8. Fatores associados à hipertensão intracraniana em crianças e adolescentes vítimas de traumatismo crânio-encefálico grave Factors associated with intracranial hypertension in children and teenagers who suffered severe head injuries

    Directory of Open Access Journals (Sweden)

    Sérgio Diniz Guerra


    Full Text Available OBJETIVO: Analisar fatores associados à ocorrência de hipertensão intracraniana em pacientes pediátricos vítimas de traumatismo crânio-encefálico (TCE grave. MÉTODOS: Coorte com coleta retrospectiva do período de 1998 a 2003. Incluídos pacientes entre 0 e 16 anos com TCE, pontuação 20 mmHg com necessidade de tratamento e HIC refratária, acima de 25 mmHg, com necessidade de coma barbitúrico ou craniectomia descompressiva. Foi realizada análise univariada, seguida de multivariada, sendo consideradas significativas as variáveis com p OBJECTIVE: To analyze factors associated with intracranial hypertension in pediatric patients who suffered severe head injuries. METHODS: Retrospective cohort study, with data collected from September 1998 through August 2003, including patients aged 0 to 16 who suffered severe head injuries, Glasgow score 20 mmHg requiring treatment, while refractory IH was ICP over 25 mmHg requiring barbiturates or decompressive craniectomy. Univariate analysis was followed by multivariate analysis; variables were considered significant if p < 0.05. RESULTS: Ages ranged from 2 months to 16 years, median age 9.7 (6.0-2.3 years. Glasgow scores ranged from 3 to 8, median 6 (4-7. Traffic accidents were responsible for 79.5% of events. Monitoring devices were installed, on average, 14 hours after trauma, median time 24 hours. One hundred and three patients (78% had IH, while 57 (43.2% had refractory IH. In multivariate analysis, younger age ranges were associated with IH relative risk = 1.67 (1.03-2.72; p = 0.037, and abnormal postures were associated with refractory IH relative risk = 2.25 (1.06-4.78. The group mortality rate was 51.5%; it was correlated with use of barbiturates in refractory IH and low cerebral perfusion pressure at the intensive care unit. CONCLUSIONS: IH and refractory IH were frequent events in pediatric patients who suffered severe head injuries. The younger the patient, the greater the chance of

  9. Spatial analysis of drug-related hospital admissions: an auto-Gaussian model to estimate the hospitalization rates in Italy

    Directory of Open Access Journals (Sweden)

    Emanuela Colasante


    Full Text Available

    Introduction: The aim of this study is to evaluate, even if partially, how much the drug use phenomenon impacts on the Italian National Heatlh System throughout the estimation at local level (Local Health Unit of the hospitalization rate caused by substance use and abuse such as opiates, barbiturates-sedativeshypnotics, cocaine and cannabis, and keeping in mind the phenomenon distribution in the space and so the fact that what happens in a specific area depends on what is happening in the neighbourhoods close to it (spatial autocorrelation.

    Methods: Data from hospital discharge database were provided by the Ministry of Health and an auto- Gaussian model was fitted. The spatial trend can be a function of other explanatory variables or can simply be modeled as a function of spatial location. Both models were fitted and compared using the number of subjects kept in charge by Drug Addiction Services and the number of beds held by hospitals as covariates.

    Results: Concerning opiates use related hospitalizations, results show areas where the phenomenon was less prominent in 2001 (Lombardy, part of Liguria, Umbria, part of Latium, Campania, Apulia and Sicily. In the following years, the hospitalization rates increased in some areas, such as the north of Apulia, part of Campania and Latium. A dependence of the opiates related hospitalization rates on the rate of subjects kept in charge by the Drug Addiction Services is highlighted. Concerning barbiturates-sedatives-hypnotics consumption, the best model is the one without covariates and estimated hospitalization rates are lower then 3 per thousand. The model with only the covariate “rate of subjects kept in charge by Drug Addiction Services” has been used both for cocaine and cannabis. In these two cases, more than a half of the Local Health Units report hospitalization rates lower than 0.5 per thousand

  10. Analysis of clinical course and magnetic resonance imaging of posttraumatic diabetes insipidus

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Yoshiaki; Hirota, Tetsuya; Kohno, Masanobu; Iwai, Atsushi; Abe, Yoshio; Ikeuchi, Hisashi; Yoshioka, Toshiharu [Osaka Prefectural General Hospital (Japan)


    We analyzed the relationship between posttraumatic diabetes insipidus (DI) onset and magnetic resonance imaging (MRI). In the last 5 years, 13 survivors of head injury were diagnosed with DI. We divided them into 2 groups, early and delayed, by DI onset. The early group consisted of 5 patients diagnosed with DI within 12 hours of injury. The delayed group consisted of 8 diagnosed after 12 hours or more. We analyzed differences between groups for factors such as Glasgow coma scale (GCS) on admission, Glasgow outcome scale (GOS) at discharge, DI duration, intracranial pressure (ICP) when diagnosed with DI, maximum ICP during observation, and MRI findings. In the early group, mean onset of DI was about 40 hours earlier than that in the delayed group, 7{+-}2 vs. 47{+-}19 hours, p<0.05. No significant differences were seen between groups for GCS, ISS, or GOS. Although no significant difference was seen in ICP, barbiturate therapy was needed in 7 cases, craniotomy in 4, and hypothermia therapy in 5 to control ICP in the delayed group. Barbiturate therapy was needed in only 2 cases and no indications were seen for craniotomy or hypothermia therapy in the early group. All cases in the delayed group recovered from DI within 3 weeks, but 3 in the early group were diagnosed with permanent DI and 1 needed antidiuretic hormone (ADH) during 75 days. All of the early group was recognized to have hypothalamic injury and diffuse axonal injury in MRI, but none in the delayed group was recognized for these MRI findings. In the delayed group, the high-intensity signal of the posterior pituitary gland in T1 weighted MRI, thought to represent the granule of ADH, disappeared in the early period and reappeared gradually after recovery from DI, but this signal did not reappear in the early group. We therefore conducted that the crucial cause of posttraumatic DI in the early group is direct hypothalamic injury, perhaps due to diffuse axonal injury, and that in the delayed group, secondary

  11. Comparative anticonvulsant activities of the essential oils (EOs) from Cymbopogon winterianus Jowitt and Cymbopogon citratus (DC) Stapf. in mice. (United States)

    Silva, Monalisa Ribeiro; Ximenes, Rafael Matos; da Costa, José Galberto Martins; Leal, L Kalyne A M; de Lopes, Amanda A; Viana, Glauce Socorro de Barros


    The fresh leaves of Cymbopogon citratus are a good source of an essential oil (EO) rich in citral, and its tea is largely used in the Brazilian folk medicine as a sedative. A similar source of EO is Cymbopogon winterianus, rich in citronellal. The literature presents more studies on the EO of C. citratus and their isolated bioactive components, but only a few are found on the EO of C. winterianus. The objective of the present study was then to study, in a comparative way, the effects of both EOs on three models of convulsions (pentylenetetrazol, pilocarpine, and strychnine) and on the barbiturate-induced sleeping time on male Swiss mice. The animals (20-30 g) were acutely treated with 50, 100, and 200 mg kg(-1), intraperitoneally, of each EO, and 30 min later, the test was initiated. The observed parameters were: latency to the first convulsion and latency to death in seconds. Furthermore, the in vitro effects of the EOs were also studied on myeloperoxidase (MPO; a biomarker for inflammation) and lactate dehydrogenase (LDH; an index of cytotoxicity) releases from human neutrophils. The EOs radical-scavenging activities were also evaluated by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The results showed that both EOs were more active on the pentylenetetrazol-induced convulsion model, and C. citratus was even more efficient in increasing latency to the first convulsion and latency to death. Both parameters were potentiated in the presence of a lower dose of diazepam (reference drug) when associated to a lower dose of each EO (25 mg kg(-1)). Besides, their anticonvulsant effects were blocked by flumazenil, a known benzodiazepine antagonist. This effect was somewhat lower on the pilocarpine-induced convulsion, and better effects were seen only with the EOs' higher doses (200 mg kg(-1)). A similar result was observed on the strychnine-induced convulsion model. Both EOs potentiated the barbiturate-induced sleeping time. However, C. citratus was more efficient

  12. Cortical neurons and networks are dormant but fully responsive during isoelectric brain state. (United States)

    Altwegg-Boussac, Tristan; Schramm, Adrien E; Ballestero, Jimena; Grosselin, Fanny; Chavez, Mario; Lecas, Sarah; Baulac, Michel; Naccache, Lionel; Demeret, Sophie; Navarro, Vincent; Mahon, Séverine; Charpier, Stéphane


    A continuous isoelectric electroencephalogram reflects an interruption of endogenously-generated activity in cortical networks and systematically results in a complete dissolution of conscious processes. This electro-cerebral inactivity occurs during various brain disorders, including hypothermia, drug intoxication, long-lasting anoxia and brain trauma. It can also be induced in a therapeutic context, following the administration of high doses of barbiturate-derived compounds, to interrupt a hyper-refractory status epilepticus. Although altered sensory responses can be occasionally observed on an isoelectric electroencephalogram, the electrical membrane properties and synaptic responses of individual neurons during this cerebral state remain largely unknown. The aim of the present study was to characterize the intracellular correlates of a barbiturate-induced isoelectric electroencephalogram and to analyse the sensory-evoked synaptic responses that can emerge from a brain deprived of spontaneous electrical activity. We first examined the sensory responsiveness from patients suffering from intractable status epilepticus and treated by administration of thiopental. Multimodal sensory responses could be evoked on the flat electroencephalogram, including visually-evoked potentials that were significantly amplified and delayed, with a high trial-to-trial reproducibility compared to awake healthy subjects. Using an analogous pharmacological procedure to induce prolonged electro-cerebral inactivity in the rat, we could describe its cortical and subcortical intracellular counterparts. Neocortical, hippocampal and thalamo-cortical neurons were all silent during the isoelectric state and displayed a flat membrane potential significantly hyperpolarized compared with spontaneously active control states. Nonetheless, all recorded neurons could fire action potentials in response to intracellularly injected depolarizing current pulses and their specific intrinsic

  13. Nuclear medicine technology progress report for quarter ending September 30, 1980

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, F.F. Jr.


    Brain uptake of several /sup 75/Se- and /sup 123m/Te-labelled barbiturates is being studied. These new agents, substituted at the C-5 position, freely pass through the intact blood-brain barrier. Barbiturates labelled with gamma-emitting radionuclides may be an attractive new class of agents for measurement of regional cerebral blood flow. The diffusion chamber assay system has been used to assess the chronic effects of As/sub 2/O/sub 3/ toxicity. A small osmotically actuated minipump was used to deliver aqueous As/sub 2/O/sub 3/ at a continuous delivery rate to animals having intraperitoneally implanted diffusion chambers containing human lung cells (Flow 200). In these preliminary studies, a 49 to 53% inhibition of cell growth was observed over a five-day period when animals received As/sub 2/O/sub 3/ at a dose of 1.7 to 2 mg (kg-d). These initial studies suggest that the minipump may be a useful means of studying the chronic effects of substances on cell proliferation in conjunction with the diffusion chamber assay system. A microscale synthesis of gold antirheumatoid agents was developed. This method involves reaction of thiohexose derivatives such as thioglucosetetraacetate (..beta..-D-TGTA) with trialkylphosphinegold halide intermediates (R/sub 3/PAu-Cl) in the presence of pyridine to give the coupling products R/sub 3/PAu(..beta..-D-TGTA) in good yield (>75%). Using this method, the triethyl analog Et/sub 3/PAu(..beta..-D-TGTA) and triphenyl analog (phi/sub 3/PAu(..beta..-D-TGTA)) have been prepared and characterized.This method will be used to prepare the /sup 195/Au-labeled agents. The platinum antitumor agent cis-dichloro-trans-dihydroxy-bis-(isopropylamine)-platinum (IV) (CHIP) has been purified. This system is efficient for separation of CHIP from impurities produced during the synthetic sequence and will be used to prepare /sup 195m/Pt-CHIP for biological evaluation. (ERB)

  14. Clinical profile and treatment outcome of febrile infection-related epilepsy syndrome in South Indian children

    Directory of Open Access Journals (Sweden)

    Sandeep B Patil


    Full Text Available Purpose: To describe the clinical features and outcome of febrile infection-related epilepsy syndrome (FIRES, a catastrophic epileptic encephalopathy, in a cohort of South Indian children. Materials and Methods: We performed a retrospective chart review of a cohort of children with previously normal development who presented with status epilepticus or encephalopathy with recurrent seizures following a nonspecific febrile illness during the period between January 2007 and January 2012. They were divided into two groups super refractory status epilepticus (SRSE and refractory status epilepticus (RSE depending on the duration and severity of the seizures. Key Findings: Fifteen children who met the inclusion criteria were included for the final analysis. The age of the children at presentation ranged 3-15 years (median 6.3 years. All the children presented with prolonged or recurrent seizures occurring 1-12 days (median 4 days after the onset of fever. Eight children had SRSE while seven children had refractory seizures with encephalopathy. Cerebrospinal fluid (CSF analysis was done in all the children in the acute phase, and the cell count ranged 0-12 cells/μL (median 2 cells/μL with normal sugar and protein levels. Initial neuroimaging done in all children (MRI in 10 and CT in 5, and it was normal in 13 children. Treatment modalities included multiple antiepileptic drugs (AEDs (4-9 drugs (median 5 drugs. Midazolam (MDZ infusion was administered in seven patients. Eight patients required barbiturate coma to suppress the seizure activity. The duration of the barbiturate coma ranged 2-90 days (median 3 days. Steroids were used in 14 children and intravenous immunoglobulin (2 g/kg in 7 children. Three children died in the acute phase. All children were maintained on multiple AEDs till the last follow-up, the number of AEDs ranged 1-6 (median 5 AEDs. The patients with super refractory status in the acute phase were found to be more severely disabled

  15. In Silico Discovery of Novel Potent Antioxidants on the Basis of Pulvinic Acid and Coumarine Derivatives and Their Experimental Evaluation. (United States)

    Martinčič, Rok; Mravljak, Janez; Švajger, Urban; Perdih, Andrej; Anderluh, Marko; Novič, Marjana


    A pigment from the edible mushroom Xerocomus badius norbadione A, which is a natural derivative of pulvinic acid, was found to possess antioxidant properties. Since the pulvinic acid represents a novel antioxidant scaffold, several other derivatives were recently synthetized and evaluated experimentally, along with some structurally related coumarine derivatives. The obtained data formed the basis for the construction of several quantitative structure-activity and pharmacophore models, which were employed in the virtual screening experiments of compound libraries and for the prediction of their antioxidant activity, with the goal of discovering novel compounds possessing antioxidant properties. A final prioritization list of 21 novel compounds alongside 8 established antioxidant compounds was created for their experimental evaluation, consisting of the DPPH assay, 2-deoxyribose assay, β-carotene bleaching assay and the cellular antioxidant activity assay. Ten novel compounds from the tetronic acid and barbituric acid chemical classes displayed promising antioxidant activity in at least one of the used assays, that is comparable to or even better than some standard antioxidants. Compounds 5, 7 and 9 displayed good activity in all the assays, and were furthermore effective preventers of oxidative stress in human peripheral blood mononuclear cells, which are promising features for the potential therapeutic use of such compounds.

  16. Hair analysis in toxicological investigation of drug-facilitated crimes in Denmark over a 8-year period. (United States)

    Wang, Xin; Johansen, Sys Stybe; Nielsen, Marie Katrine Klose; Linnet, Kristian


    Hair can serve as a specimen for identifying past drug exposure. Segmental hair analysis may differentiate a single exposure from chronic use. Consequently, segmental hair analysis is useful for disclosing a single drug ingestion, as well as for determining repeated exposures in drug-facilitated crimes (DFCs). This paper presents an overview of toxicological investigations that have used hair analysis in DFC cases from 2009 to 2016 in Denmark. Hair concentrations were determined for 24 DFC-related drugs and metabolites, including benzodiazepines and other hypnotics, antihistamines, opioid analgesics, antipsychotics, barbiturates, and illicit drugs from DFC cases. Drug detection in hair in DFC cases following a single or few intakes of chlorprothixene, codeine, diphenhydramine, oxazepam, oxycodone, promethazine, and phenobarbital is reported for the first time in forensic toxicology. A literature review on concentrations in the published DFC-related hair cases and on concentrations in hair of these substances after single and multiple doses is included. These cases demonstrate the value of segmental hair analysis in DFCs and facilitate future interpretations of results. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Protein tethering enables rapid and label-free SERS platform for screening drugs of abuse (Conference Presentation) (United States)

    Siddhanta, Soumik; Wróbel, Maciej S.; Barman, Ishan


    A quick, cost-effective method for detection of drugs of abuse in biological fluids would be of great value in healthcare, law enforcement, and home testing applications. The alarming rise in narcotics abuse has led to considerable focus on developing potent and versatile analytical tools that can address this societal problem. While laboratory testing plays a key role in the current detection of drug misuse and the evaluation of patients with drug induced intoxication, these typically require expensive reagents and trained personnel, and may take hours to complete. Thus, a significant unmet need is to engineer a facile method that can rapidly detect drugs with little sample preparation, especially the bound fraction that is typically dominant in the blood stream. Here we report an approach that combines the exquisite sensitivity of surface enhanced Raman spectroscopy (SERS) and a facile protein tethering mechanism to reliably detect four different classes of drugs, barbiturate, benzodiazepine, amphetamine and benzoylecgonine. The proposed approach harnesses the reliable and specific attachment of proteins to both drugs and nanoparticle to facilitate the enhancement of spectral markers that are sensitive to the presence of the drugs. In conjunction with chemometric tools, we have shown the ability to quantify these drugs lower than levels achievable by existing clinical immunoassays. Through molecular docking simulations, we also probe the mechanistic underpinnings of the protein tethering approach, opening the door to detection of a broad class of narcotics in biological fluids within a few minutes as well as for groundwater analysis and toxin detection.

  18. [Drug testing with use of POCT]. (United States)

    Komiyama, Yutaka


    Drug testing with the use of point of care testing (POCT) has been widely used in Japan, especially in the field of drug abuse, poisoning, and anticoagulant therapy with warfarin. For evidence-based medicine of POCT, an interesting report was presented by the National Academy of Clinical Biochemistry in the United States as the guideline in 2006. Users of POCT devices should understand all limitations of the devices. This strength/consensus recommendation is strong and the level of evidence is high. In this field, cyan, arsenic, paraquat, organic phosphate, methanol, acetaminophen, barbiturates, benzodiazepines, antidepressants, and some other drugs were detected by POCT devices such as Triage DOA and a detector tube system and others in Japan. The usefulness of the organophosphorus pesticide detection kit in the accident of GYOZA POISONING from china was noteworthy. In the case of toluene intoxication, the detector tube system was useful as a screening test for the gas phase test of a 2-year-old patient's vomit and excreta without any information from his parents. In warfarin treatment, a POCT device was useful for small hospitals and clinics. Although the cost is not covered by the health insurance system in Japan, the emergency centers of hospitals use these POCT devices for clinical decision-making. This is the most important problem.

  19. Antinociceptive and antiallodynic effects of Momordica charantia L. in tibial and sural nerve transection-induced neuropathic pain in rats. (United States)

    Jain, Vivek; Pareek, Ashutosh; Paliwal, Nishant; Ratan, Yashumati; Jaggi, Amteshwar Singh; Singh, Nirmal


    This study was designed to investigate the ameliorative potential of Momordica charantia L. (MC) in tibial and sural nerve transection (TST)-induced neuropathic pain in rats. TST was performed by sectioning tibial and sural nerve portions (2 mm) of the sciatic nerve, and leaving the common peroneal nerve intact. Acetone drop, pin-prick, hot plate, paint-brush, and walking track tests were performed to assess cold allodynia, mechanical and heat hyperalgesia, and dynamic mechanical allodynia and tibial functional index, respectively. The levels of tumour necrosis factor (TNF)-alpha and thio-barbituric acid reactive substances (TBARS) were measured in the sciatic nerve as an index of inflammation and oxidative stress. MC (all doses, orally, once daily) was administered to the rats for 24 consecutive days. TST led to significant development of cold allodynia, mechanical and heat hyperalgesia, dynamic mechanical allodynia, and functional deficit in walking along with rise in the levels of TBARS and TNF-alpha. Administration of MC (200, 400, and 800 mg/kg) significantly attenuated TST-induced behavioural and biochemical changes. Furthermore, pretreatment of BADGE (120 mg/kg, intraperitoneally) abolished the protective effect of MC in TST-induced neuropathic pain. Collectively, it is speculated that PPAR-gamma agonistic activity, anti-inflammatory, and antioxidative potential is critical for antinociceptive effect of MC in neuropathic pain.

  20. Acute poisoning in a children's hospital: a 2-year experience. (United States)

    Fazen, L E; Lovejoy, F H; Crone, R K


    In a 2-year retrospective review, 90 patients were treated in a children's hospital for acute overdoses. In 90%, the history was the most important indicator of poisoning. On physical examination, 64% of patients were found to have altered sensorium, and 69% of cases were confirmed with a routine qualitative toxicology screening test. Accidental overdoses were most frequently due to ingestion of petroleum distillates, digoxin, carbamazepine, and theophylline. Suicidal patients ingested alcohol, barbiturates, tricyclic antidepressants, benzodiazepines, and aspirin. The majority of children with accidental overdoses received medical attention within 2 hours, but suicidal patients presented significantly later. Appropriate treatment with gastric lavage or emesis was used for 85% of patients on an emergency basis prior to admission. The inpatient therapy is based on continued gastrointestinal decontamination, basic organ system support, and monitoring for toxic effects and complications of therapy. Specific antidotes were available for only 10% of patients. In this study, 50% of patients were able to be discharged to their homes after one day of hospitalization. Pediatric patients treated in the intensive care unit incur less morbidity than adults in a similar setting. Adolescents who attempt suicide and are treated in the intensive care unit are likely to take prescription drugs in a similar manner as their adult counterparts.

  1. Imprinting of cerebral cytochrome P450s in offsprings prenatally exposed to cypermethrin augments toxicity on rechallenge (United States)

    Singh, Anshuman; Agrahari, Anita; Singh, Radhadutt; Yadav, Sanjay; Srivastava, Vikas; Parmar, Devendra


    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. Further, bisulphite sequencing revealed critical CpG methylation changes in BARBIE BOX (Barbiturate response element) and BTE (Basal transcription element) in promoter of CYP2B1 in the brain isolated from rechallenged animals. Western blotting and DNA laddering/fragmentation studies revealed a greater magnitude of increase in the signalling pathways associated with apoptosis in the rechallenged animals. The data have indicated that overexpression of cerebral CYPs could be due to the imprinting of CYPs. Further, increased apoptosis observed in the rechallenged offsprings has suggested that these epigenetic changes in CYPs may predispose the prenatally exposed offsprings to the neurotoxic effects of other centrally acting drugs and chemicals when subsequently rechallenged later at life.

  2. Serum thyroid hormones and tissue 5'-monodeiodinase activity in acutely thyroidectomized newborn lambs

    Energy Technology Data Exchange (ETDEWEB)

    Polk, D.H.; Wu, S.Y.; Fisher, D.A.


    After either total thyroidectomy or sham operation in full-term fetal sheep, fetuses were delivered and serial blood samples were obtained for measurements of thyroxine (T4), triiodothyronine (T3), and catecholamines. Despite comparable serum T4 values, serum T3 values were lower in the thyroidectomized animals. Four hours after birth, the animals were killed with an intravenous overdose of barbiturate. Brain, thyroid, liver, kidney, and brown adipose tissues were dissected and analyzed for thyroxine 5'-monodeiodinase (5'-MDI) activity in vitro. 5'-MDI activity was comparable in all tissues from sham-operated and thyroidectomized lambs. Plasma epinephrine and norepinehprine concentrations, mean arterial pressure, mean pulse, rectal temperature, and arterial blood gas values were similar in the two groups of animals. These data support the hypothesis that the thyroid gland is the major source of T3 for the T3 surge in the immediate newborn period. They also indicate that the neonatal T3 surge has limited immediate metabolic significance in euthyroid newborns.

  3. Drugs Used in Sexual Assaults: Features and Toxicological Investigations

    Directory of Open Access Journals (Sweden)

    Pinar Efeoglu


    Full Text Available Drugs used in sexual assault, which are also called as date rape drugs, are common phenomenon of crime in many countries. In a typical scenario, a perpetrator adds a date-rape drug which has sedative effect into alcoholic or non-alcoholic beverage of an unsuspecting person. After drug administration, mostly amnesia and symptoms such as confussion, loss of memory, lack of muscle control, dizziness occur. The main drugs in sexual assaults are benzodiazepines such as γ-hydroxy butyrate and its analogs, clonazepam, alprazolam, flunitrazepam, oxazepam, ketamine, barbiturates, antidepressants, cocaine and stimulants. Most of these drugs are colorless, odorless and highly soluble in alcohol or other beverages quickly. They are rapidly absorbed and eliminated after oral administration. A victim may complain to police or other legal forces after several days due to emotional trauma as shame, fear, doubt and disbelief. For this reason, It is important to know what time the sample is taken from the victim to confirm the presence of the drug. In this study, we will present a general approach to date-rape drugs used in sexual assault. [Archives Medical Review Journal 2013; 22(3.000: 418-425

  4. Developing a specialty: J.S. Lundy's three major contributions to anesthesiology. (United States)

    Ellis, Terry A; Narr, Bradly J; Bacon, Douglas R


    John S. Lundy was able to accomplish three major goals during the early years of his stewardship of the section on anesthesia of the Mayo Clinic. In 1925, Lundy established the first anatomy lab at the Mayo Clinic. He believed that the lab would serve as a useful tool for teaching residents as well as research into regional anesthetic techniques. Second, Lundy desired to advance the science of anesthesiology. Lundy developed the concept of balanced anesthesia, pioneered the introduction of barbiturates to the practice of anesthesia, developed anesthesia section services for the use of ventilators, ventilator vests, oxygen tents, and nasal oxygen supplementation. Lastly, in 1935, he established the nation's first blood bank. Lundy and Ralph Tovell had the opportunity to do pioneering work in transfusion medicine, which led to an improvement in the quality of service, and patient safety. These three major accomplishments provided Lundy with abundant scientific material to present to the American Medical Association (AMA) in Chicago. These trips to Chicago allowed him to gain the ear of Olin West, Morris Fishbien, and James E. Pallin. Lundy was able to successfully lobby in 1939 for the creation of a section of anesthesia within the AMA. In 1940, Lundy's dream came true with the recognition of anesthesia as a specialty by the AMA.

  5. Physiologic, Behavioral, and Histologic Responses to Various Euthanasia Methods in C57BL/6NTac Male Mice (United States)

    Boivin, Gregory P; Bottomley, Michael A; Schiml, Patricia A; Goss, Lori; Grobe, Nadja


    Rodent euthanasia using exposure to increasing concentrations of CO2 has come under scrutiny due to concerns of potential pain during the euthanasia process. Alternatives to CO2, such as isoflurane and barbiturates, have been proposed as more humane methods of euthanasia. In this study, we examined 3 commonly used euthanasia methods in mice: intraperitoneal injection of pentobarbital–phenytoin solution, CO2 inhalation, and isoflurane anesthesia followed by CO2 inhalation. We hypothesized that pentobarbital–phenytoin euthanasia would cause fewer alterations in cardiovascular response, result in less behavioral evidence of pain or stress, and produce lower elevations in ACTH than would the isoflurane and CO2 methods, which we hypothesized would not differ in regard to these parameters. ACTH data suggested that pentobarbital–phenytoin euthanasia may be less stressful to mice than are isoflurane and CO2 euthanasia. Cardiovascular, behavioral, and activity data did not consistently or significantly support isoflurane or pentobarbital–phenytoin euthanasia as less stressful methods than CO2. Euthanasia with CO2 was the fastest method of the 3 techniques. Therefore, we conclude that using CO2 with or without isoflurane is an acceptable euthanasia method. Pathologic alterations in the lungs were most severe with CO2 euthanasia, and alternative euthanasia techniques likely are better suited for studies that rely on analysis of the lungs. PMID:28905718

  6. Pentobarbital Toxicity after Self-Administration of Euthasol Veterinary Euthanasia Medication

    Directory of Open Access Journals (Sweden)

    Steven Jason Crellin


    Full Text Available Suicide attempt via sodium pentobarbital is uncommon. A 48-year-old woman with a history of depression and prior suicide attempt was found unresponsive by her veterinarian spouse near a syringe containing pink solution. Upon EMS’ arrival, the patient was experiencing apnea, hypoxemia, and miotic pupils; her blood glucose level measured 73 mg/dL. She was bradycardic and administered atropine with transient improvement in heart rate and transported to an emergency department; 2 mg of intravenous naloxone was administered without effect. She was endotracheally intubated via rapid sequence intubation. Rapid urine drug screening detected both benzodiazepines and barbiturates. The patient was transferred to an intensive care unit where she demonstrated a nearly absent radial pulse. Emergent fasciotomy to the left forearm and carpal tunnel was performed for acute compartment syndrome; “Euthasol” had been self-administered into the antecubital fossa. Expanded toxicological analysis via liquid chromatography/mass spectroscopy detected caffeine, atropine, 7-aminoclonazepam, phenytoin, citalopram, and naproxen. The patient’s coma resolved over 48 hours and she was successfully extubated without complication. Emergency physicians must closely monitor patients exposed to veterinary euthanasia agents who develop central nervous system and respiratory depression, hypothermia, bradycardia, hypotension, or skin injury. Consultation with a regional poison center and medical toxicologist is recommended.

  7. Biochemical study of multiple drug recognition sites on central benzodiazepine receptors

    Energy Technology Data Exchange (ETDEWEB)

    Trifiletti, R.R.


    The benzodiazepine receptor complex of mammalian brain possesses recognition sites which mediate (at least in part) the pharmacologic actions of the 1,4-benzodiazepines and barbiturates. Evidence is provided suggesting the existence of least seven distinct drug recognition sites on this complex. Interactions between the various recognition sites have been explored using radioligand binding techniques. This information is utilized to provide a comprehensive scheme for characterizing receptor-active drugs on an anxiolytic-anticonvulsant/proconvulsant continuum using radioligand binding techniques, as well as a comprehensive program for identifying potential endogenous receptor-active substances. Further evidence is provided here supporting the notion of benzodiazepine recognition site heterogeneity. Classical 1,4-benzodiazepines do not appear to differentiate two populations of benzodiazepine receptors in an equilibrium sense, but appear to do so in a kinetic sense. An apparent physical separation of the two receptor subtypes can be achieved by differential solubilization. The benzodiazepine binding subunit can be identified by photoaffinity labeling with the benzodiazepine agonist (/sup 3/H)flunitrazepan. Conditions for reproducible partial proteolytic mapping of (/sup 3/H)flunitrazepam photoaffinity labeled receptors are established. From these maps, it is concluded that there are probably no major differences in the primary sequence of the benzodiazepine binding subunit in various regions of the rat central nervous system.

  8. Update of Inpatient Treatment for Refractory Chronic Daily Headache. (United States)

    Lai, Tzu-Hsien; Wang, Shuu-Jiun


    Chronic daily headache (CDH) is a group of headache disorders, in which headaches occur daily or near-daily (>15 days per month) and last for more than 3 months. Important CDH subtypes include chronic migraine, chronic tension-type headache, hemicrania continua, and new daily persistent headache. Other headaches with shorter durations (CDH. Common comorbidities of CDH are medication overuse headache and various psychiatric disorders, such as depression and anxiety. Indications of inpatient treatment for CDH patients include poor responses to outpatient management, need for detoxification for overuse of specific medications (particularly opioids and barbiturates), and severe psychiatric comorbidities. Inpatient treatment usually involves stopping acute pain, preventing future attacks, and detoxifying medication overuse if present. Multidisciplinary integrated care that includes medical staff from different disciplines (e.g., psychiatry, clinical psychology, and physical therapy) has been recommended. The outcomes of inpatient treatment are satisfactory in terms of decreasing headache intensity or frequency, withdrawal from medication overuse, reducing disability, and improving life quality, although long-term relapse is not uncommon. In conclusion, inpatient treatment may be useful for select patients with refractory CDH and should be incorporated in a holistic headache care program.

  9. Fingerprinting groundwater pollution in catchments with contrasting contaminant sources using microorganic compounds. (United States)

    Stuart, Marianne E; Lapworth, Dan J; Thomas, Jenny; Edwards, Laura


    Evaluating the occurrence of microorganics helps to understand sources and processes which may be controlling the transport and fate of emerging contaminants (ECs). A study was carried out at the contrasting instrumented environmental observatory sites at Oxford, on the peri-urban floodplain gravel aquifer of the River Thames and Boxford, in the rural valley of the River Lambourn on the chalk aquifer, in Southern England to explore the use of ECs to fingerprint contaminant sources and flow pathways in groundwater. At Oxford compounds were typical of a local waste tip plume (not only plasticisers and solvents but also barbiturates and N,N-diethyl-m-toluamide (DEET)) and of the urban area (plasticisers and mood-enhancing drugs such as carbamazepine). At Boxford the results were different with widespread occurrence of agricultural pesticides, their metabolites and the solvent trichloroethene, as well as plasticisers, caffeine, butylated food additives, DEET, parabens and trace polyaromatic hydrocarbons (PAHs). Groups of compounds used in pharmaceuticals and personal care products of different provenance in the environment could be distinguished, i) historical household and medical waste, ii) long-term household usage persistent in groundwater and iii) current usage and contamination from surface water. Co-contaminant and degradation products can also indicate the likely source of contaminants. A cocktail of contaminants can be used as tracers to provide information on catchment pathways and groundwater/surface water interactions. A prominent feature in this study is the attenuation of many EC compounds in the hyporheic zone. © 2013.

  10. A comparison of anesthetic agents and their effects on the response properties of the peripheral auditory system. (United States)

    Dodd, F; Capranica, R R


    Anesthetic agents were compared in order to identify the most appropriate agent for use during surgery and electrophysiological recordings in the auditory system of the tokay gecko (Gekko gecko). Each agent was first screened for anesthetic and analgesic properties and, if found satisfactory, it was subsequently tested in electrophysiological recordings in the auditory nerve. The following anesthetic agents fulfilled our criteria and were selected for further screening: sodium pentobarbital (60 mg/kg); sodium pentobarbital (30 mg/kg) and oxymorphone (1 mg/kg); 3.2% isoflurane; ketamine (440 mg/kg) and oxymorphone (1 mg/kg). These agents were subsequently compared on the basis of their effect on standard response properties of auditory nerve fibers. Our results verified that different anesthetic agents can have significant effects on most of the parameters commonly used in describing the basic response properties of the auditory system in vertebrates. We therefore conclude from this study that the selection of an appropriate experimental protocol is critical and must take into consideration the effects of anesthesia on auditory responsiveness. In the tokay gecko, we recommend 3.2% isoflurane for general surgical procedures; and for electrophysiological recordings in the eighth nerve we recommend barbiturate anesthesia of appropriate dosage in combination if possible with an opioid agent to provide additional analgesic action.

  11. The historical significance of anaesthesia events at Pearl Harbor. (United States)

    Crowhurst, Ja


    Up to the end of World War II, less than 10% of the general anaesthetics administered was with intravenous barbiturates. The remaining 90% of anaesthetics given in the USA were with diethyl ether. In the United Kingdom and elsewhere, chloroform was also popular. Diethyl ether administration was a relatively safe and simple procedure, often delegated to nurses or junior doctors with little or no specific training in anaesthesia. During the Japanese attack on the US bases at Pearl Harbor, with reduced stocks of diethyl ether available, intravenous Sodium Pentothal(®), a most 'sophisticated and complex' drug, was used with devastating effects in many of those hypovolaemic, anaemic and septic patients. The hazards of spinal anaesthesia too were realised very quickly. These effects were compounded by the dearth of trained anaesthetists. This paper presents the significance of the anaesthesia tragedies at Pearl Harbor, and the discovery in the next few years of many other superior drugs that caused medical and other health professionals to realise that anaesthesia needed to be a specialist medical discipline in its own right. Specialist recognition, aided by the foundation of the National Health Service in the UK, the establishment of Faculties of Anaesthesia and appropriate training in pharmacology, physiology and other sciences soon followed. Modern anaesthesiology, as we understand it today, was born and a century or more of ether anaesthesia finally ceased.

  12. Crystal structure of 4-aminopyridinium 5-(5-chloro-2,4-dinitrophenyl-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate hemihydrate

    Directory of Open Access Journals (Sweden)

    Manickkam Vaduganathan


    Full Text Available The title molecular salt, C5H7N2+·C12H8ClN4O7−·0.5H2O, crystallizes as a hemihydrate. The two rings in the barbiturate anion are not coplanar but make a dihedral angle of 43.17 (16°. The two nitro groups deviate from the ring to which they are attached; the nitro group ortho with respect to the ring junction is more deviated [39.3 (4°] than that in the para position [4.2 (5°], probably to overcome steric hindrance. As a result of this, the latter nitro group is more involved in delocalizing the negative charge of the anion than the former nitro group. In the crystal, the cations and anions are linked via N—H...O hydrogen bonds forming zigzag chains along [10-1]. The chains are linked by O—H...O and C—H...O hydrogen bonds, forming slabs lying parallel to (10-1. Further C—H...O hydrogen bonds link the slabs, forming a three-dimensional structure.

  13. The Effect of KIO3 and KI Salt towards Iodium Levels (I2 in Urine, Malondialdehyde (MDA and Histological Thyroid Gland of The Goitrogenic Rat

    Directory of Open Access Journals (Sweden)

    Chanif Mahdi


    Full Text Available Goitrogenic a substance that can inhibit the taking of iodine by the thyroid gland, so that the concentration of iodine in the thyroid to be low., is characterized by the inflammation in the gland thyroid area caused an excessive of free radicals. An excessive of free radicals in the body cause oxidative stress, That increasing the levels of malondialdehyde (MDA as an indicator of lipid peroxidation and decreased levels of urinary iodine excretion levels (EIU. The treated to give KIO3 and KI salt was intended to determine the level of supplementation of iodine (I2, the level of MDA in serum and histological rat thyroid gland. MDA levels are determined through a TBA test (Thio Barbituric acid, meanwhile the histological of the rat thyroid gland was determined by Hematoxylen-Eosin staining (HE. The results showed the KIO3 and KI salt was significantly (p<0.05 reduce levels of MDA in the serum of treatment with KIO3 salt (33.62% and KI salt (37,02% and improving histological of the thyroid gland rats.


    Directory of Open Access Journals (Sweden)

    K. Sinaga


    Full Text Available The effect of andaliman fruit juice marination on the amounts of benzo (a pyrene in charcoal grilled duck meat were investigated in this research. Completely randomized design was used to determine the effect of 4 treatments of andaliman fruit juice concentration (w/v. Twenty four duck meat samples were devided into 4 treatment groups, those were 0% (I, 10% (II, 20% (III and 30% (IV. Each group consisted of 6 samples. Total Fat, Tio Barbituric Acid (TBA value and antioxidant activity were measured from all samples. The result showed there was no effect on total fat of duck meat. Antioxidant activity was 18.60 %, 18.06 %, 19.99 % and 7.54 % for andaliman fruit juice of 10%, 20%, 30% and 0%, respectively. TBA value was 1.03 %, 0.89 %, 0.09 % and 0.10 % for treatment II, III, IV and I, respectively. Antioxidant activity of andaliman fruit was decreased the amounts of Benzo (a pyrene of duckmeat. Charcoal duck meat without andaliman fruit produced 787 ng, it was higher than charcoal duck meat with andaliman fruit (295 ng.

  15. The Effect of KIO3 and KI Salt Towards Iodium Levels (I2 in Urine, Malondialdehyde (MDA and The Histology of Thyroid Gland of Goitrogenic Rat

    Directory of Open Access Journals (Sweden)

    Risman Heli


    Full Text Available Goitrogenic substances can inhibit of iodine taking by the thyroid gland. Thus iodine concentration in thyroid gland will be low, and this phenomena is indicated by inflammation in the thyroid gland. Moreover, it can cause releaseing of an excessive amount of free radicals. This radicals, in the body, causes oxidative stress and also increase the levels of malondialdehyde (MDA. This is also as an indicator for lipid peroxidation and the decreasing of urinary iodine excretion levels (EIU. The treatment with KIO3 and KI salt was intended to study the level of supplementation of iodine (I2 toward level of MDA in serum and histological description of rat’s thyroid gland. The MDA levels was determined through TBA test (Thio Barbituric Acid, meanwhile the histological pattern of rat thyroid gland was determined by Hematoxylen-Eosin staining (HE. The results indicated both of KIO3 and KI salt significantly (p<0.01 reduced MDA level in the serum. Treatment with KIO3 salt gave 33.62% while KI salt slightly higher (37,02%. In addition, both of treaments displayed an recovering effect in thyroid gland.

  16. Voltammetric determination of polyphenolic content in pomegranate juice using a poly(gallic acid/multiwalled carbon nanotube modified electrode

    Directory of Open Access Journals (Sweden)

    Refat Abdel-Hamid


    Full Text Available A simple and sensitive poly(gallic acid/multiwalled carbon nanotube modified glassy carbon electrode (PGA/MWCNT/GCE electrochemical sensor was prepared for direct determination of the total phenolic content (TPC as gallic acid equivalent. The GCE working electrode was electrochemically modified and characterized using scanning electron microscope (SEM, cyclic voltammetry (CV, chronoamperometry and chronocoulometry. It was found that gallic acid (GA exhibits a superior electrochemical response on the PGA/MWCNT/GCE sensor in comparison with bare GCE. The results reveal that a PGA/MWCNT/GCE sensor can remarkably enhance the electro-oxidation signal of GA as well as shift the peak potentials towards less positive potential values. The dependence of peak current on accumulation potential, accumulation time and pH were investigated by square-wave voltammetry (SWV to optimize the experimental conditions for the determination of GA. Using the optimized conditions, the sensor responded linearly to a GA concentration throughout the range of 4.97 × 10−6 to 3.38 × 10−5 M with a detection limit of 3.22 × 10−6 M (S/N = 3. The fabricated sensor shows good selectivity, stability, repeatability and (101% recovery. The sensor was successfully utilized for the determination of total phenolic content in fresh pomegranate juice without interference of ascorbic acid, fructose, potassium nitrate and barbituric acid. The obtained data were compared with the standard Folin–Ciocalteu spectrophotometric results.

  17. Effect of carboxymethyl cellulose edible coating containing Zataria multiflora essential oil and grape seed extract on chemical attributes of rainbow trout meat

    Directory of Open Access Journals (Sweden)

    Mojtaba Raeisi


    Full Text Available Meat products, especially fish meat, are very susceptible to lipid oxidation and microbial spoilage. In this study, first, gas chromatography mass spectrometry (GC-MS analysis of Zataria multiflora essential oil (ZEO components was done and then two concentrations of ZEO, (1% and 2% and two concentrations of grape seed extract (GSE, (0.5% and 1% were used in carboxymethyl cellulose coating alone and in combination, and their antioxidant effects on rainbow trout meat were evaluated in a 20-day period using thiobarbituric acid reactive substances (TBARS test. Their effects on total volatile basic nitrogen (TVBN and pH were evaluated as well. The main components of ZEO are thymol and carvacrol. These components significantly decreased production of thio-barbituric acid (TBA, TVBN and pH level of fish meat. The initial pH, TVBN and TBA content was 6.62, 12.67 mg N per 100 g and 0.19 mg kg-1, respectively. In most treatments significant (p < 0.05 effects on aforementioned factors was seen during storage at 4 ˚C. The results indicated that use of ZEO and GSE as a natural antioxidant agents was effective in reducing undesirable chemical reactions in storage of fish meat.

  18. The effects of exposure of {sup 60}Co on the oxidant/antioxidant status among radiation victims

    Energy Technology Data Exchange (ETDEWEB)

    Demir, Mustafa E-mail:; Konukoglu, Dildar; Kabasakal, Levent; Yelke, Hakan Kadir; Ergen, Kadir; Ahmed, Sabbir


    This retrospective study has been performed with radiation victims who were accidentally exposed to a {sup 60}Co source and its release into the environment. The aim of the study was to assess the effects of elevated radiation exposures on plasma level, on erythrocyte thio barbituric acid reactive substance (TBARS) level and on erythrocyte glutathione (GSH) levels. Patients were treated in different hospitals with different symptoms such as nausea, vomiting, dizziness, along with severe anemia in some patients. Blood samples were collected 3-5 days following the radiation accident. Increases in plasma (6.25{+-}0.90 nmol ml{sup -1}) and erythrocyte TBARS levels (330.5{+-}30.5 {mu}mol gHb{sup -1}) were found in comparison to a healthy group (3.72{+-}0.68 nmol ml{sup -1} and 150.7{+-}20.5 {mu}mol gHb{sup -1}, respectively) at a significant level (p<0.001). Erythrocyte GSH levels (5.2{+-}0.30 {mu}mol gHb{sup -1}) were found to be decreased among the victims (healthy group: 10.2{+-}0.7 {mu}mol gHb{sup -1}) at the same significance level (p<0.001). These observations confirm a significant change induced by radiation in the oxidant/antioxidant status among the victims. It is suggested here that antioxidant supplementation therapy might be effective in preventing the harmful effects of {sup 60}Co radiation among radiation victims.

  19. Pemanfaatan Ekstrak Air Daun Jambu Biji Sebagai Antioksidan Alami Pada Pengolahan Patin Asin

    Directory of Open Access Journals (Sweden)

    Farida Ariyani


    Full Text Available Penelitian pemanfaatan ekstrak air daun jambu biji (Psidium guajava sebagai antioksidan alami pada pengolahan patin asin telah dilakukan. Aplikasi ekstrak air daun jambu dilakukan dengan merendam ikan dalam campuran larutan garam dan ekstrak daun jambu. Konsentrasi larutan garam yang digunakan adalah 30%, sedangkan variasi konsentrasi ekstrak daun jambu yang digunakan adalah 0, 6, dan 12% (w/v. Perendaman dalam larutan garam dilakukan selama 48 jam dengan perbandingan antara ikan dan larutan yang digunakan untuk merendam 1:2 (b/v. Selesai penggaraman, ikan dibelah menjadi bentuk butterfly kemudian dikeringkan di bawah sinar matahari sampai kering (4–5 hari. Pengamatan dilakukan terhadap sifat sensori, kadar air, angka Thio Barbituric Acid (TBA, produk berfluoresen dan proporsi asam lemak tidak jenuh patin asin. Hasil percobaan menunjukkan bahwa penambahan ekstrak air daun jambu pada larutan garam jenuh dengan konsentrasi 6 dan 12% selama penggaraman mampu menghambat oksidasi lemak patin asin yang tercermin dari penghambatan peningkatan kadar TBA, produk berfluoresen dan penghambatan kerusakan asam lemak tidak jenuh selama penyimpanan 2 bulan. Hasil uji sensori memperlihatkan bahwa patin asin yang diberi perlakuan memberikan bau yang tidak tengik, walaupun warna patin menjadi lebih coklat. Berdasarkan pertimbangan hasil secara kimiawi maupun sensori, perlakuan ekstrak daun jambu pada konsentrasi 6% merupakan perlakuan terpilih

  20. Acetone Extract from Rhodomyrtus tomentosa: A Potent Natural Antioxidant

    Directory of Open Access Journals (Sweden)

    Goodla Lavanya


    Full Text Available Rhodomyrtus tomentosa (Myrtaceae has been employed in traditional Thai medicine to treat colic diarrhoea, dysentery, abscesses, haemorrhage, and gynaecopathy. In addition, it has been used to formulate skin-whitening, anti-aging and skin beautifying agents. Ethnomedical activities of this plant may be due its antioxidant property. Hence, the aim of this study was to evaluate both in vitro and in vivo antioxidant activities of R. tomentosa leaf extract. In vitro antioxidant activity of the extract was assessed by lipid peroxidation inhibition capacity, ferric reducing antioxidant power, and metal chelating activity. R. tomentosa extract demonstrated its free radical scavenging effects in concentration dependent manner. In vivo antioxidant activity of the extract was conducted in Swiss Albino mice. Levels of thio-barbituric acid reactive substances (TBARS, glutathione (GSH, and the activities of antioxidant enzymes including superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GPx in blood, liver, and kidney were analyzed using microtitre plate photometer. Administration of CCl4 caused significant increase in TBARS and decrease in GSH, SOD, CAT and GPx levels. In contrast, R. tomentosa extract (0.8 g/kg effectively prevented these alterations and maintained the antioxidant status. The results suggest that R. tomentosa extract can serve as a potent antioxidant.

  1. Sonochemically assisted hollow/solid BaTiO3:Dy3+ microspheres and their applications in effective detection of latent fingerprints and lip prints

    Directory of Open Access Journals (Sweden)

    M. Dhanalakshmi


    Full Text Available Nanostructured materials find potential benefits for surface-based science such as latent fingerprints (LFPs and lip print detection on porous and non-porous surfaces. To encounter the drawbacks viz. low sensitivity, high background hindrance, complicated procedure and high toxicity associated with traditional fluorescent powders were resolved by using hollow/solid BaTiO3:Dy3+ (1–5 mol % microspheres. The visualization of LFPs stained by the optimized BaTiO3:Dy3+ (2 mol % hollow/solid microspheres exhibits well-defined ridge patterns with high sensitivity, low background hindrance, high efficiency and low toxicity on various surfaces. The powder X-ray diffraction results revealed the body centered cubic phase of the prepared samples. The emission spectra exhibit intensive peaks at ∼480, 575, and 637 nm, which were attributed to transitions 4F9/2→6HJ (J = 15/2, 13/2, 11/2 of Dy3+ ions, respectively. Surface morphologies were extensively studied with different sonication times and concentrations of the used barbituric acid. The Commission International De I-Eclairage (CIE and Correlated Color Temperature (CCT analyses revealed that the present phosphor is highly useful for the fabrication of white light emitting diodes.

  2. Molecular Architectural Approach to Novel Electro-Optical Materials

    Energy Technology Data Exchange (ETDEWEB)

    Li, D.; Johal, M.S.; Smilowitz, L.B.; Robinson, J.M.


    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). The goal is to construct polar multilayers with nonlinear optical coefficients larger than classical inorganic crystals such as KDP or quartz. The strategy is to use various chemical interactions such as covalent bonds or hydrogen bonding to build polar structures. We have synthesized novel barbituric acid and melamine derivatives that will spontaneously self-assemble into a supramolecular ribbon according to their complementary H-bond motif. This supramolecular ribbon can then stack into a polar multilayer structure as verified by sum frequency generation (w{sub 1}+w{sub 2}) or second harmonic generation (when w{sub 1}=w{sub 2}). Second harmonic generation yields a value of d{sub 33}=3.2 pm/V for the self-assembled films and sum frequency generation shows a net polar orientation of the methyl groups in the multilayer along the surface normal. X-ray diffraction confirms the layered structure and produces the periodicity of {approximately}41 A, which corresponds well to the width of the supramolecular ribbons ({approximately}40 A).

  3. Development of novel (1-H benzimidazole bearing pyrimidine-trione based MAO-A inhibitors: Synthesis, docking studies and antidepressant activity

    Directory of Open Access Journals (Sweden)

    Bijo Mathew


    Full Text Available The synthesis of some novel (1-H benzimidazole bearing pyrimidine-trione based MAO-A inhibitors were achieved by the reaction between 2E-1-(1H-benzimidazol-2-yl-3-phenylprop-2-en-1-ones(4a–f and barbituric acid in the presence of a catalytic amount of acetic acid medium. All the final structures were assigned on the basis of IR, 1HNMR and mass spectra analyses. All the synthesized derivatives showed good antidepressant activity when compared to the standard clomipiramine at a dose level of 20 mg/kg. The compound (5d 5-{(2E-1-(1H-benzimidazol-2-yl-3-[4-(dimethylaminophenyl] prop-2-en-1-ylidene} pyrimidine-2, 4, 6(1H,3H,5H-trione significantly reduced the duration of immobility times at 50 mg/kg−1 dose level when compared to the standard drug. Molecular docking studies revealed the need for an extra hydrophobic interaction in the titled scaffold for acquiring the promising experimental values. It has been concluded that the computational values obtained after the docking calculation are in good agreement with the experimental values.

  4. Exploring the potential effect of Ocimum sanctum in vincristine-induced neuropathic pain in rats

    Directory of Open Access Journals (Sweden)

    Jaggi Amteshwar


    Full Text Available Abstract The present study was designed to investigate the ameliorative potential of Ocimum sanctum and its saponin rich fraction in vincristine-induced peripheral neuropathic pain in rats. Peripheral neuropathy was induced in rats by administration of vincristine sulfate (50 μg/kg i.p. for 10 consecutive days. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species (TBARS, super-oxide anion content (markers of oxidative stress and total calcium levels were measured. Vincristine administration was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia. Furthermore, vincristine administration was also associated with an increase in oxidative stress and calcium levels. However, administration of Ocimum sanctum (100 and 200 mg/kg p.o. and its saponin rich fraction (100 and 200 mg/kg p.o. for 14 days significantly attenuated vincristine-induced neuropathic pain along with decrease in oxidative stress and calcium levels. It may be concluded that Ocimum sanctum has ameliorative potential in attenuating chemotherapy induced-painful neuropathic state, which may be attributed to decrease in oxidative stress and calcium levels. Furthermore, saponin rich fraction of Ocimum sanctum may be responsible for its noted beneficial effect in neuropathic pain in rats.

  5. Hybrid process for nitrogen oxides reduction

    Energy Technology Data Exchange (ETDEWEB)

    Epperly, W.R.; Sprague, B.N.


    This patent describes a process for reducing the nitrogen oxide concentration in the effluent from the combustion of a carbonaceous fuel. It comprises introducing into the effluent a first treatment agent comprising a nitrogenous composition selected from the group consisting of urea, ammonia, hexamethylenetetramine, ammonium salts of organic acids, 5- or 6-membered heterocyclic hydrocarbons having at least one cyclic nitrogen, hydroxy amino hydrocarbons, NH{sub 4}-lignosulfonate, fur-furylamine, tetrahydrofurylamine, hexamethylenediamine, barbituric acid, guanidine, guanidine carbonate, biguanidine, guanylurea sulfate, melamine, dicyandiamide, biuret, 1.1{prime}-azobisformamide, methylol urea, methylol urea-urea condensation product, dimethylol urea, methyl urea, dimethyl urea, calcium cyanamide, and mixtures thereof under conditions effective to reduce the nitrogen oxides concentration and ensure the presence of ammonia in the effluent; introducing into the effluent a second treatment agent comprising an oxygenated hydrocarbon at an effluent temperature of about 500{degrees} F. to about 1600{degrees} F. under conditions effective to oxidize nitric oxide in the effluent to nitrogen dioxide and ensure the presence of ammonia at a weight ratio of ammonia to nitrogen dioxide of about 1:5 to about 5:1; and contacting the effluent with an aqueous scrubbing solution having a pH of 12 or lower under conditions effective to cause nitrogen dioxide to be absorbed therein.

  6. Ameliorative potential of Ocimum sanctum in chronic constriction injury-induced neuropathic pain in rats

    Directory of Open Access Journals (Sweden)



    Full Text Available The present study was designed to investigate the ameliorative potential of Ocimumsanctum and its saponin rich fraction in chronic constriction injury-induced neuropathic pain in rats. The chronic constriction injury was induced by placing four loose ligatures around the sciatic nerve, proximal to its trifurcation. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species, super-oxide anion content (markers of oxidative stress and total calcium levels were measured. Chronic constriction injury was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia along with an increase in oxidative stress and calcium levels. However, administration of Ocimumsanctum (100 and 200 mg/kg p.o. and its saponin rich fraction (100 and 200 mg/kg p.o. for 14 days significantly attenuated chronic constriction injury-induced neuropathic pain as well as decrease the oxidative stress and calcium levels. It may be concluded that saponin rich fraction of Ocimum sanctum has ameliorative potential in attenuating painful neuropathic state, which may be attributed to a decrease in oxidative stress and calcium levels.

  7. 2-Methylpyridinium/pyridinium 5-(2,4-dinitrophenyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olates as potent anticonvulsant agents—synthesis and crystal structure

    Energy Technology Data Exchange (ETDEWEB)

    Mangaiyarkarasi, G.; Kalaivani, D., E-mail: [Affiliated to Bharathidasan University, Post Graduate and Research Department of Chemistry, Seethalakshmi Ramaswami College, Tiruchirappalli-620 002 (India)


    The molecular salt, 2-methylpyridinium 5-(2,4-dinitrophenyl)-2,6-dioxo-1,2,3,6-tetrahydropy-rimidin-4-olate) (I), is prepared from the ethanolic solution of 1-chloro-2,4-dinitrobenzene, pyrimidine-2,4,6-(1H,3H,5H)-trione (barbituric acid) and 2-methylpyridine at room temperature, and the molecular salt, pyridinium 5-(2,4-dinitrophenyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate (II), is prepared from the same reactants, by dissolving them in hot DMSO and ethanol mixture at 70°C. The structures of I and II are characterized by visible, IR, {sup 1}H-NMR, {sup 13}C-NMR and elemental analysis and confirmed by single crystal X-ray analysis. Both the salts crystallize in triclinic crystal system with sp. gr. P-bar1. They possess noticeable anticonvulsant activity even at low concentration (25 mg/kg). Acute toxicity studies of these complexes indicate that LD{sub 50} values are greater than 1500 mg/kg and the tested animals do not show any behavioural changes.

  8. In Silico Discovery of Novel Potent Antioxidants on the Basis of Pulvinic Acid and Coumarine Derivatives and Their Experimental Evaluation.

    Directory of Open Access Journals (Sweden)

    Rok Martinčič

    Full Text Available A pigment from the edible mushroom Xerocomus badius norbadione A, which is a natural derivative of pulvinic acid, was found to possess antioxidant properties. Since the pulvinic acid represents a novel antioxidant scaffold, several other derivatives were recently synthetized and evaluated experimentally, along with some structurally related coumarine derivatives. The obtained data formed the basis for the construction of several quantitative structure-activity and pharmacophore models, which were employed in the virtual screening experiments of compound libraries and for the prediction of their antioxidant activity, with the goal of discovering novel compounds possessing antioxidant properties. A final prioritization list of 21 novel compounds alongside 8 established antioxidant compounds was created for their experimental evaluation, consisting of the DPPH assay, 2-deoxyribose assay, β-carotene bleaching assay and the cellular antioxidant activity assay. Ten novel compounds from the tetronic acid and barbituric acid chemical classes displayed promising antioxidant activity in at least one of the used assays, that is comparable to or even better than some standard antioxidants. Compounds 5, 7 and 9 displayed good activity in all the assays, and were furthermore effective preventers of oxidative stress in human peripheral blood mononuclear cells, which are promising features for the potential therapeutic use of such compounds.

  9. Microwave assisted one-pot catalyst free green synthesis of new methyl-7-amino-4-oxo-5-phenyl-2-thioxo-2,3,4,5-tetrahydro-1H-pyrano[2,3-d]pyrimidine-6-carboxylates as potent in vitro antibacterial and antifungal activity

    Directory of Open Access Journals (Sweden)

    Ajmal R. Bhat


    Full Text Available An efficiently simple protocol for the synthesis of methyl 7 amino-4-oxo-5-phenyl-2-thioxo-2, 3, 4,5-tetrahydro-1H-pyrano[2,3-d]pyrimidine-6-carboxylates via one-pot three component condensation pathway is established via microwave irradiation using varied benzaldehyde derivatives, methylcyanoacetate and thio-barbituric acid in water as a green solvent. A variety of functionalized substrates were found to react under this methodology due to its easy operability and offers several advantages like, high yields (78–94%, short reaction time (3–6 min, safety and environment friendly without used any catalyst. The synthesized compounds (4a–4k showed comparatively good in vitro antimicrobial and antifungal activities against different strains. The Compounds 4a, 4b, 4c, 4d 4e and 4f showed maximum antimicrobial activity against Staphylococcus aureus, Bacillus cereus (gram-positive bacteria, Escherichia coli, Klebshiella pneumonia, Pseudomonas aeruginosa (gram-negative bacteria. The synthesized compound 4f showed maximum antifungal activity against Aspergillus Niger and Penicillium chrysogenum strains. Streptomycin is used as standard for bacterial studies and Mycostatin as standards for fungal studies. Structure of all newly synthesized products was characterized on the basis of IR, 1H NMR, 13C NMR and mass spectral analysis.

  10. Orotidine-5'-monophosphate decarboxylase catalysis: Kinetic isotope effects and the state of hybridization of a bound transition-state analogue

    Energy Technology Data Exchange (ETDEWEB)

    Acheson, S.A.; Bell, J.B.; Jones, M.E.; Wolfenden, R. (Univ. of North Carolina School of Medicine, Chapel Hill (USA))


    The enzymatic decarboxylation of orotidine 5'-monophosphate may proceed by an addition-elimination mechanism involving a covalently bound intermediate or by elimination of CO2 to generate a nitrogen ylide. In an attempt to distinguish between these two alternatives, 1-(phosphoribosyl)barbituric acid was synthesized with 13C at the 5-position. Interaction of this potential transition-state analogue inhibitor with yeast orotidine-5'-monophosphate decarboxylase resulted in a small (0.6 ppm) downfield displacement of the C-5 resonance, indicating no rehybridization of the kind that might have been expected to accompany 5,6-addition of an enzyme nucleophile. When the substrate orotidine 5'-monophosphate was synthesized with deuterium at C-5, no significant change in kcat (H/D = 0.99 +/- 0.06) or kcat/KM (H/D = 1.00 +/- 0.06) was found to result, suggesting that C-5 does not undergo significant changes in geometry before or during the step that determines the rate of the catalytic process. These results are consistent with a nitrogen ylide mechanism and offer no support for the intervention of covalently bound intermediates in the catalytic process.

  11. Buthalital and methitural – 5,5-substituted derivatives of 2-thiobarbituric acid forming the same type of hydrogen-bonded chain

    Directory of Open Access Journals (Sweden)

    Thomas Gelbrich


    Full Text Available The molecule of buthalital, (I [systematic name: 5-(2-methylpropyl-5-(prop-2-en-1-yl-2-sulfanylidene-1,3-diazinane-4,6-dione], C11H16N2O2S, exhibits a planar pyrimidine ring, whereas the pyrimidine ring of methitural, (II [systematic name: 5-(1-methylbutyl-5-[2-(methylsulfanylethyl]-2-sulfanylidene-1,3-diazinane-4,6-dione], C12H20N2O2S2, is slightly puckered. (I and (II contain the same hydrogen-bonded chain structure in which each molecule is connected, via four N—H...O=C hydrogen bonds, to two other molecules, resulting in a hydrogen-bonded chain displaying a sequence of R22(8 rings. The same type of N—H...O=C hydrogen-bonded chain has previously been found in several 5,5-disubstituted derivatives of barbituric acid which are chemically closely related to (I and (II.

  12. Drugs of abuse consumption in health professionals (physicians and nurses from two outpatient services of first level attention in Bogota

    Directory of Open Access Journals (Sweden)

    Lara-Hidalgo Catalina


    Full Text Available We conducted a study to establish the prevalence of drugs of abuse consumption in physiciansand nurses in two health institutions in Bogota outpatient identify the frequency of consumption,to establish the prevalence of alcoholism using the CAGE questionnaire and explore the interestparticipate in prevention or reduction of consumption in the workplace. Materials and methods: Across-sectional study by applying an anonymous survey. Results: There were 58 questionnaires (38in physicians and 20 nurses. The substances most consumed in both groups were alcohol, cigarettesand energy drinks, followed on medical by marijuana in nursing followed by barbiturates, antidepressants,amphetamines and opiates. The prevalence of alcoholism was greater than 8% in bothgroups. 58% of physicians and 70% of nurses would participate in the design of occupational healthprograms to reduce the consumption of psychoactive substances. Conclusions: The use of drugs ofabuse is higher that found in the literature for most of the substances in the general population andis similar to the revised health personnel. It recommends the formulation and implementation ofcorporate policy within the framework of occupational health work of these institutions, aimed atreducing and preventing the consumption of psychoactive substances.

  13. Reduction in radiation-induced brain injury by use of pentobarbital or lidocaine protection

    Energy Technology Data Exchange (ETDEWEB)

    Oldfield, E.H.; Friedman, R.; Kinsella, T.; Moquin, R.; Olson, J.J.; Orr, K.; DeLuca, A.M. (National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (USA))


    To determine if barbiturates would protect brain at high doses of radiation, survival rates in rats that received whole-brain x-irradiation during pentobarbital- or lidocaine-induced anesthesia were compared with those of control animals that received no medication and of animals anesthetized with ketamine. The animals were shielded so that respiratory and digestive tissues would not be damaged by the radiation. Survival rates in rats that received whole-brain irradiation as a single 7500-rad dose under pentobarbital- or lidocaine-induced anesthesia was increased from between from 0% and 20% to between 45% and 69% over the 40 days of observation compared with the other two groups (p less than 0.007). Ketamine anesthesia provided no protection. There were no notable differential effects upon non-neural tissues, suggesting that pentobarbital afforded protection through modulation of ambient neural activity during radiation exposure. Neural suppression during high-dose cranial irradiation protects brain from acute and early delayed radiation injury. Further development and application of this knowledge may reduce the incidence of radiation toxicity of the central nervous system (CNS) and may permit the safe use of otherwise unsafe doses of radiation in patients with CNS neoplasms.


    Directory of Open Access Journals (Sweden)

    Aguslina kirtishanti dan Dini Kesuma


    Full Text Available The study on the development of benzoylthiourea derivatives as central nervous system (CNS depressants was based on their structure, which contains acyclic ureide, an isosteric group of CNS depressant drugs common structure. The study was carried out by modifying the structure of benzoylthiourea using the Topliss model based on the enhancement of its lipophilic and electronic properties. It is predicted that the product will give higher activity than the parent compound. In this study, identification of CNS depressant, anticonvulsant and neurotoxicity effects of the compound synthesized, i.e. 4-chlorobenzoylthiourea, was conducted. The identification of CNS depressant effects was done using Barbiturate Sleeping Time, the identification of anticonvulsant effects was done using Maximum Electroshock Seizure and the identification of neurotoxicity effect was done using rotarod in mice (Mus musculus. This study used five groups of mice: a control group, a standard group (Phenobarbital Na and 3 treatment groups with doses of 15 mg/kg, 45 mg/kg and 75 mg/kg respectively. From the results, it can be concluded that 4-chlorobenzoylthiourea gives the best CNS depressant, anticonvulsant and neurotoxicity effects at the doses of 75 mg/kg, 15 mg/kg and 45 mg/kg respectively. 


    Directory of Open Access Journals (Sweden)

    Aguslina kirtishanti dan Dini Kesuma


    Full Text Available The study on the development of benzoylthiourea derivatives as central nervous system (CNS depressants was based on their structure, which contains acyclic ureide, an isosteric group of CNS depressant drugs common structure. The study was carried out by modifying the structure of benzoylthiourea using the Topliss model based on the enhancement of its lipophilic and electronic properties. It is predicted that the product will give higher activity than the parent compound. In this study, identification of CNS depressant, anticonvulsant and neurotoxicity effects of the compound synthesized, i.e. 4-chlorobenzoylthiourea, was conducted. The identification of CNS depressant effects was done using Barbiturate Sleeping Time, the identification of anticonvulsant effects was done using Maximum Electroshock Seizure and the identification of neurotoxicity effect was done using rotarod in mice (Mus musculus. This study used five groups of mice: a control group, a standard group (Phenobarbital Na and 3 treatment groups with doses of 15 mg/kg, 45 mg/kg and 75 mg/kg respectively. From the results, it can be concluded that 4-chlorobenzoylthiourea gives the best CNS depressant, anticonvulsant and neurotoxicity effects at the doses of 75 mg/kg, 15 mg/kg and 45 mg/kg respectively.

  16. [Effect of insulin on retinal glycogen content]. (United States)

    Lansel, N; Rungger-Brändle, E; Hitz-Kueng, N; Niemeyer, G


    The effect of insulin on glucose and glycogen metabolism in peripheral organs is well known. However, information about the action of this peptide in the retina is incomplete. We addressed the questions whether insulin influences glycogen content in the cat retina and whether glycogen breakdown is triggered by lack of glucose. Eyes from adult cats were enucleated under deep barbiturate and fentanylanesthesia. Retinas were snap frozen either before or following arterial in vitro perfusion. Three conditions were studied: a) Perfusion with a glucose- and insulin-free medium; b) perfusion with the addition of physiologic glucose concentration; and c) in combination with insulin. Glycogen content was determined by in vitro measurement of glucose converted from glycogen. The reference value for retinal glycogen after enucleation (10 min of ischemia) is 2.4 micrograms glucose/mg protein. Glucose- and insulin-free perfusion for 80 min following "normoglycemia" reduced the amount of retinal glycogen by one third. Perfusion for 3 h with 5.5 mM glucose led to a small increase of the partly depleted glycogen stores. Insulin, in contrast, markedly augmented the glycogen content. Insulin led to an increase in retinal glycogen content, indicating an influence of this peptide on retinal glucose and glycogen metabolism. However, it appears that glycogen might play a dynamic role in retinal metabolism as a buffer between abrupt changes in focal metabolic demands that occur during normal glucose supply rather than acting solely as an emergency energy reserve for neural function during hypoglycemia.

  17. Catatonia: a syndrome appears, disappears, and is rediscovered. (United States)

    Fink, Max


    Catatonia is the psychiatric syndrome of disturbed motor functions amid disturbances in mood and thought first described in 1874. It was quickly found in 10% to 38% of psychiatric populations. After it was tied to schizophrenia as a type in the psychiatric classification, its recognition became increasingly limited and by the 1980s questions were asked as to where the catatonics had gone. The decline is largely owing to the change in venue for psychiatric practice from asylum to office, the rejection of physical examination, and the dependence on item rating scales for diagnosis. In the 1970s, broad surveys again showed that catatonia was as common as before among patients with mania and depression, and as a toxic response to neuroleptic drugs. The latter recognition, that the neuroleptic malignant syndrome is the same syndrome as malignant catatonia, and is effectively treated as such, sparked a renewed interest. Clinicians developed rating scales to identify the catatonia syndrome and applied the immediate relief afforded by a barbiturate or a benzodiazepine as a diagnostic test, the lorazepam test. Effective treatments were described as high doses of benzodiazepines and electroconvulsive therapy (ECT). Surveys using catatonia rating scales showed catatonia to have many faces. Catatonia is presently limited to a type of schizophrenia in the psychiatric classification. Its recognition as a disorder of its own, such as delirium and dementia, should now be recognized. This experience reinforced the utility of the medical model for diagnosis. An application for melancholia is described.

  18. Catatonia is not schizophrenia and it is treatable. (United States)

    Appiani, Francisco J; Castro, Gonzalo S


    Catatonia is a cluster of motor features that appears in many recognized psychiatric illnesses, that according to the DSM-5 it is not linked as a subtype to schizophrenia anymore. The classic signs are mutism, a rigid posture, fixed staring, stereotypic movements, and stupor, which are all part of a broad psychopathology that may be found in affective, thought, neurological, toxic, metabolic and immunological disorders. Despite the many etiologies, catatonia may be a life-threatening condition with a specific treatment. Benzodiazepines are the first line therapeutic option for catatonia, being lorazepam the first-choice drug. Eighty percent of the patients are relieved by the use of barbiturates or benzodiazepines, while in those who fail, an improvement is achieved by electroconvulsive therapy (ECT). With more than 60years of use in catatonic patients, ECT has proven to be an effective and safe tool for the treatment of this frequent and sometimes forgotten syndrome. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Interlaboratory studies with the Chinese hamster V79 cell metabolic cooperation assay to detect tumor-promoting agents

    Energy Technology Data Exchange (ETDEWEB)

    Bohrman, J.S.; Burg, J.R.; Elmore, E.; Gulati, D.K.; Barfknecht, T.R.; Niemeier, R.W.; Dames, B.L.; Toraason, M.; Langenbach, R.


    Three laboratories participated in an interlaboratory study to evaluate the usefulness of the Chinese hamster V79 cell metabolic cooperation assay to predict the tumor-promoting activity of selected chemical. Twenty-three chemicals of different chemical structures (phorbol esters, barbiturates, phenols, artificial sweeteners, alkanes, and peroxides) were chosen for testing based on in vivo promotion activities, as reported in the literature. Assay protocols and materials were standardized, and the chemicals were coded to facilitate unbiased evaluation. A chemical was tested only once in each laboratory, with one of the three laboratories testing only 15 out of 23 chemicals. Dunnett's test was used for statistical analysis. Chemicals were scored as positive (at least two concentration levels statistically different than control), equivocal (only one concentration statistically different), or negative. For 15 chemicals tested in all three laboratories, there was complete agreement among the laboratories for nine chemicals. For the 23 chemicals tested in only two laboratories, there was agreement on 16 chemicals. With the exception of the peroxides and alkanes, the metabolic cooperation data were in general agreement with in vivo data. However, an overall evaluation of the V79 cell system for predicting in vivo promotion activity was difficult because of the organ specificity of certain chemicals and/or the limited number of adequately tested nonpromoting chemicals.

  20. A Massive Overdose of Dalfampridine

    Directory of Open Access Journals (Sweden)

    Laura J. Fil


    Full Text Available Multiple sclerosis (MS is an immune mediated inflammatory disease that attacks myelinated axons in the central nervous system. Dalfampridine (4-aminopyridine was approved by the Food and Drug Administration in January 2010 for treatment of MS. Our patient was a 34-year-old male with a history of MS, who was brought to the emergency department after being found unresponsive. His current medications were valacyclovir, temazepam, dalfampridine (4-AP and a tysabri intravenous (IV infusion. Fifteen minutes after arrival the patient seized. The seizures were refractory to benzodiazepines, barbiturates and phenytoin. The 4-AP level was 530ng/mL (25ng/mL and 49ng/ mL. The patient stopped seizing on hospital day 3 and was discharged 14 days later with normal mental status and neurologic exam. 4-AP is a potassium channel blocker that blocks the potassium ion current of repolarization following an action potential. The blockade of the potassium channel at the level of the membrane widens the action potential and enhances the release of acetylcholine, thus increasing post-synaptic action potentials. The treatment of patients with 4-AP overdose is supportive. Animal data suggest that patients with toxic levels of 4-AP may respond to phenytoin. Our case illustrates the highest recorded level of 4-AP in an overdose. Our patient appeared to be refractory to a combination of high doses of anticonvulsants and only improved with time.

  1. Autoregulation of spinal cord blood flow: is the cord a microcosm of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Hickey, R.; Albin, M.S.; Bunegin, L.; Gelineau, J.


    The autoregulatory capability of regional areas of the brain and spinal cord was demonstrated in 18 rats anesthetized with a continuous infusion of intravenous pentothal. Blood flow was measured by the injection of radioactive microspheres (Co57, Sn113, Ru103, Sc46). Blood flow measurements were made at varying levels of mean arterial pressure (MAP) which was altered by neosynephrine to raise MAP or trimethaphan to lower MAP. Autoregulation of the spinal cord mirrored that of the brain, with an autoregulatory range of 60 to 120 mm Hg for both tissues. Within this range, cerebral blood flow (CBF) was 59.2 +/- 3.2 ml/100 g/min (SEM) and spinal cord blood flow (SCBF) was 61.1 +/- 3.6. There was no significant difference in CBF and SCBF in the autoregulatory range. Autoregulation was also demonstrated regionally in the left cortex, right cortex, brainstem, thalamus, cerebellum, hippocampus and cervical, thoracic and lumbar cord. This data provides a coherent reference point in establishing autoregulatory curves under barbiturate anesthesia. Further investigation of the effects of other anesthetic agents on autoregulation of the spinal cord is needed. It is possible that intraspinal cord compliance, like intracranial compliance, might be adversely affected by the effects of anesthetics on autoregulation.

  2. Some radiopharmaceuticals derived from carbon-eleven labelled phosgene

    International Nuclear Information System (INIS)

    Roeda, D.


    This thesis deals with some applications of the short lived cyclotron produced radioisotope carbon-11 (half life 20.4 min.) For medical use. Both chemical manipulation of highly radioactive gamma emitting material in order to prepare suitable 11 C-labelled radiopharmaceuticals and two clinical studies are discussed. The first chapter comprises a general introduction concerning the application of the ''tracer principle'' to the short lived positron emitting radionuclides 18 F, 11 C, 13 N and 15 O in medicine. Chapter two deals with the synthesis of 11 COCl 2 . This product is a useful new 11 C-synthon with many potential applications. In chapter three the synthesis of 11 C-urea from 11 C-phosgene for medical use is described. The method uses the reaction of 11 COCl 2 with aqueous ammonia. Chapter four deals with the synthesis of 11 C-barbituric acids and 11 C-hydantoins and presents a clinical study on epilepsy, using 2- 11 C-5,5-diphenylhydantoin ( 11 C-DPH). Patients having intractable epilepsy and patients having no epilepsy were given intravenously a single dose of 11 C-DPH after which the accumulation of the radioactivity in the brain was followed by positron emission tomography. No regional concentration differences could be found near epileptic foci. There was a faint indication that there are some differences in uptake for whole brain between the two categories of patients. (Auth.)

  3. Actions of insecticides on the insect GABA receptor complex

    Energy Technology Data Exchange (ETDEWEB)

    Bermudez, I.; Hawkins, C.A.; Taylor, A.M.; Beadle, D.J. (School of Biological and Molecular Sciences, Oxford Polytechnic, Headington, Oxford (England))


    The actions of insecticides on the insect gamma-aminobutyric acid (GABA) receptor were investigated using (35S)t-butylbicyclophosphorothionate (( 35S)TBPS) binding and voltage-clamp techniques. Specific binding of (35S)TBPS to a membrane homogenate derived from the brain of Locusta migratoria locusts is characterised by a Kd value of 79.3 {plus minus} 2.9 nM and a Bmax value of 1770 {plus minus} 40 fmol/mg protein. (35S)TBPS binding is inhibited by mM concentrations of barbiturates and benzodiazepines. In contrast dieldrin, ivermectin, lindane, picrotoxin and TBPS are inhibitors of (35S)TBPS binding at the nanomolar range. Bicuculline, baclofen and pyrethroid insecticides have no effect on (35S)TBPS binding. These results are similar to those obtained in electrophysiological studies of the current elicited by GABA in both Locusta and Periplaneta americana central neurones. Noise analysis of the effects of lindane, TBPS, dieldrin and picrotoxin on the cockroach GABA responses reveals that these compounds decrease the variance of the GABA-induced current but have no effect on its mean open time. All these compounds, with the exception of dieldrin, significantly decrease the conductance of GABA-evoked single current.


    Directory of Open Access Journals (Sweden)

    O. A. Pylaeva


    Full Text Available Attention deficit hyperactivity disorder (ADHD is the most common cause of behavioral disorders and learning problems at preschool and school ages. Patients with ADHD are frequently found to have comorbidities that present additional diagnostic and therapeutic problems and result in an even greater decrease in quality of life in patients. Thus, ADHD is frequently concurrent with epilepsy; in this case, not only the manifestations of ADHD are more common in epilepsy, but the latter is more often encountered in patients with ADHD than in those as a whole. The authors consider the epidemiological factors and causes, which may lead to a concurrence of these two diseases in the same patient, the principles of diagnosis and differential diagnosis of ADHD in epileptic patients, the specific features of treatment in this patient category. At the same time, the authors place emphasis on the fact that some antiepileptic drugs, such as barbiturates, may cause symptoms that mimic ADHD (in these cases, inattention and hyperactivity are adverse reactions of therapy and lessen or disappear after drug discontinuation or enhance the manifestations of ADHD in patients with a concurrence of these two diseases. On the other hand, care should be also taken to choose drugs for the treatment of ADHD due to the possible higher frequency of seizures. So preference should be given to the drugs having no negative effect on the course of comorbidities or those having a positive therapeutic effect against both diseases. 

  5. The Nigella Sativa seed extract protects γ-radiation induced GI damage in rats and PMA induced PKC inhibition in macrophages only in pretreated condition

    International Nuclear Information System (INIS)

    Pandey, Nidhi; Kumar, Mohan; Tripathi, Yamini Bhusan


    Bone marrow and gastro intestinal (GI) cells are more sensitive to radiation induced damages, due to presence of actively proliferating cell. The radiation induces apoptosis through generating oxidative stress. Here the protective effect of non-polar hexane fraction of seeds of Nigella sativa Linn. (NS) (NSH) has been explored on GI damage. The NSH was orally given to albino rats, in pre (90 min) and post treatment whole body irradiation (WBI) by 60 Co gamma radiation for further 14 days. The NSH significantly raised the survival rate of animals. It further prevented the radiation (4 Gy) induced suppression in the activity of super oxide dismutase (SOD) and catalase and rise in Thio barbituric acid reactive substances (TBARS) on 7 days post-irradiation. Histo-pathological examinations revealed significant protection of ileum cells. It restored the radiation-induced reduction in villous height and crypt number and prevented the focal mucosal erosion, congestion and loss of villi. The response was dose dependent at lower concentrations only, suggesting its use as food supplement for the patients undergoing radiotherapy. At higher doses, opposite results were observed. The mechanism of action was proposed through its FR scavenging potential as it prevented the PMA induced PKC expression only when added in the pretreatment condition or within 2 min of PMA addition to macrophage culture. Late addition had no protective response. (author)

  6. Use of clonidine in the prevention and management of neonatal abstinence syndrome. (United States)

    Leikin, Jerrold B; Mackendrick, William P; Maloney, Gerry E; Rhee, James W; Farrell, Elaine; Wahl, Michael; Kelly, Karen


    Neonatal abstinence syndrome (NAS) is a complicated medical condition with treatment regimens that traditionally have included methadone and other opioids, barbiturates, and benzodiazepines. We describe a case series in which clonidine was used for the prevention and management of patients with NAS. Medical records of infants treated with clonidine for NAS from January 2003 to March 2006 were reviewed for gestational age, birth weight, NAS score, dose of clonidine, duration of treatment, and additional medications required. Fourteen patients were identified. The mean gestational age was 30.1 weeks (range 24.4-40.7 weeks); three patients were full-term. Eleven had been on intravenous fentanyl for sedation; three were born to opioid-dependent mothers. All patients were treated with clonidine, administered in doses of 0.5-1.0 mcg/kg orally every 6 h. No patient received opioids. Mean duration of treatment was 6.8 days (range 4-15). Mean abstinence scores were 6.4 pretreatment (range 0-20) and 1.9 posttreatment (range 0-5). No patients suffered an adverse event (hypotension, bradycardia, excessive sedation, and oxygen desaturation) from clonidine administration, and no seizures were identified. Our data suggest that clonidine may be a reasonable alternative to more traditional agents used to prevent or treat NAS. We agree with the statement of the American Academy of Pediatrics Committee on Drugs that states that larger trials and pharmacologic data are needed before the routine use of clonidine can be recommended.

  7. Evaluation of nootropic potential of Ocimum sanctum Linn. in mice. (United States)

    Joshi, Hanumanthachar; Parle, Milind


    Dementia is one of the age related mental problems and a characteristic symptom of various neurodegenerative disorders including Alzheimer's disease. Certain drugs like diazepam, barbiturates and alcohol disrupt learning and memory in animals and man. However, a new class of drugs known as nootropic agents is now used in situations where there is organic disorder in learning abilities. The present work was undertaken to assess the potential of O. sanctum extract as a nootropic and anti-amnesic agent in mice. Aqueous extract of dried whole plant of O. sanctum ameliorated the amnesic effect of scopolamine (0.4 mg/kg), diazepam (1 mg/kg) and aging induced memory deficits in mice. Elevated plus maze and passive avoidance paradigm served as the exteroceptive behavioral models. O. sanctum extract decreased transfer latency and increased step down latency, when compared to control (piracetam treated), scopolamine and aged groups of mice significantly. O. sanctum preparations could of beneficial in the treatment of cognitive disorders such as dementia and Alzheimer's disease.

  8. Hypoxic encephalopathy after heart valve replacement: etiology and pathogenesis, diagnostic criteria and treatment

    Directory of Open Access Journals (Sweden)

    В. Г. Постнов


    Full Text Available Reviewed in this paper are modern approaches in the intensive therapy of acute hypoxic encephalopathy developing in a number of occasions after the heart valve replacement surgery. The study is based on the results of neurological, neuropsychological and neurophysiological (EEG examinations of 240 patients who underwent heart valve replacement surgery under cardiopulmonary bypass conditions complicated later by the development of hypoxic encephalopathies of varying severity and who received complex intensive care. Relying on many years of experience in the treatment of heart surgery patients in whom manifestations of encephalopathy developed in the early postoperative period, or were delayed, we have formulated the following algorithms of therapy. (1 Maintenance of normal blood gas: Hb>100 g/L, pH 7.45, PaCO2 35 mmHg. (2 Maintenance of hemodynamics: ABPsystolic>90 mmHg. (3 Supplying fluids and electrolytes: isoosmolar infusion solutions, adding of KCl and MgSO4 to the infusion. (4 Antiedemic therapy: 15% mannitol or 40% glycerol solution. (5 If necessary (in case of psychomotor agitation, seizures, short-acting barbiturates (sodium thiopental, neuroleptics (haloperidol, propofol. No benzodiazepines in case of psychoses (6 Cerebral metabolism stimulation (not earlier than 48 hours after surgery with cholinomimetics, nootropics, cerebral blood flow protectors. Cholinomimetics are allowed on the first day after surgery. This algorithm and the above-mentioned groups of drugs, especially central cholinomimetics, allow for correcting the neurocognitive impairment in the discussed group of patients quickly and effectively.

  9. Halothane anaesthesia and liver damage A review of the literature on this and associated hazards

    CERN Document Server

    Spoor, N L


    In radiological protection the decision to use bronchopulmonary lavage, or not to use it, will occasionally rest on a comparison of risks: on the one hand the long-term radiological risk and, on the other, the short-term risks from the operation itself (after several repetitions) and from multiple exposure to the anaesthetic agents, thiopentone (or other barbiturate) and halothane. The purpose of this review was to find a numerical estimate for the risk of irreversible liver damage from multiple exposure to halothane in a healthy male aged between 20 and 60 years. The many reports which have appeared since 1970 have shown that halothane hepatitis is probably a specific, but rare, pathological condition and that the risks from halothane exposure are no greater than those from other anaesthetics. The facts suggest that there is an increased risk associated with multiple exposure. If for the average patient the mortality risk from one anaesthetic exposure to halothane is 1 in 10 sup 5 , the risk from two further...

  10. Pharmacological classification of the abuse-related discriminative stimulus effects of trichloroethylene vapor. (United States)

    Shelton, Keith L; Nicholson, Katherine L


    Inhalants are distinguished as a class primarily based upon a shared route of administration. Grouping inhalants according to their abuse-related in vivo pharmacological effects using the drug discrimination procedure has the potential to provide a more relevant classification scheme to the research and treatment community. Mice were trained to differentiate the introceptive effects of the trichloroethylene vapor from air using an operant procedure. Trichloroethylene is a chlorinated hydrocarbon solvent once used as an anesthetic as well as in glues and other consumer products. It is now primarily employed as a metal degreaser. We found that the stimulus effects of trichloroethylene were similar to those of other chlorinated hydrocarbon vapors, the aromatic hydrocarbon toluene and the vapor anesthetics methoxyflurane and isoflurane. The stimulus effects of trichloroethylene overlapped with those of the barbiturate methohexital, to a lesser extent the benzodiazepine midazolam and to ethanol. NMDA antagonists, the kappa opioid agonist U50,488 and the mixed 5-HT agonist mCPP largely failed to substitute for trichloroethylene. These data suggest that stimulus effects of chlorinated hydrocarbon vapors are mediated at least partially by GABA A receptor positive modulatory effects.

  11. Medications and impaired driving. (United States)

    Hetland, Amanda; Carr, David B


    To describe the association of specific medication classes with driving outcomes and provide clinical recommendations. The MEDLINE and EMBASE databases were searched for articles published from January 1973 to June 2013 on classes of medications associated with driving impairment. The search included outcome terms such as automobile driving, motor vehicle crash, driving simulator, and road tests. Only English-language articles that contained findings from observational or interventional designs with ≥ 10 participants were included in this review. Cross-sectional studies, case series, and case reports were excluded. Driving is an important task and activity for the majority of adults. Some commonly prescribed medications have been associated with driving impairment measured by road performance, driving simulation, and/or motor vehicle crashes. This review of 30 studies identified findings with barbiturates, benzodiazepines, hypnotics, antidepressants, opioid and nonsteroidal analgesics, anticonvulsants, antipsychotics, antiparkinsonian agents, skeletal muscle relaxants, antihistamines, anticholinergic medications, and hypoglycemic agents. Additional studies of medication impact on sedation, sleep latency, and psychomotor function, as well as the role of alcohol, are also discussed. Psychotropic agents and those with central nervous system side effects were associated with measures of impaired driving performance. It is difficult to determine if such associations are actually a result of medication use or the medical diagnosis itself. Regardless, clinicians should be aware of the increased risk of impaired driving with specific classes of medications, educate their patients, and/or consider safer alternatives.

  12. [Obstetric and gynecologic anesthesia reported in the "Revista Española de Obstetricia y Ginecología" (1916-1936)]. (United States)

    Llorente, A; Giménez, M C; Figueira, A; Montero, G


    This study follows the evolution of anesthesia in gynecology and obstetrics in Spain between 1916 and 1936. Research included revising all articles and references concerning anesthesiology appearing in the Revista Española de Obstetricia y Ginecologia over the 20 years during which that journal was published. Eighty-three articles were found: 18 (21.6%) original research reports, 37 (44.6%) reviews of the Spanish professional literature and 28 (33.7%) summaries and descriptions of meetings of scientific organizations. Spanish references constituted 39.8% with the remaining 60.2% coming from European and Hispano-American sources. Twenty-four (34.9%) were related to spinal anesthesia, 15 (18%) covered various methods for analgesia during childbirth and 14 (16.8%) were on barbiturates. The remaining articles referred to rectally administered anesthesia, local anesthesia, inhalatory anesthesia and pain in gynecology. In conclusion, our review reveals the strong international contacts in Spanish gynecology during this period, as well as the interest of gynecologists and obstetricians in various anesthetic techniques and the rapid incorporation of new methods into their therapeutic arsenal.

  13. Therapeutic implications of melatonin in cerebral edema. (United States)

    Rathnasamy, Gurugirijha; Ling, Eng-Ang; Kaur, Charanjit


    Cerebral edema/brain edema refers to the accumulation of fluid in the brain and is one of the fatal conditions that require immediate medical attention. Cerebral edema develops as a consequence of cerebral trauma, cerebral infarction, hemorrhages, abscess, tumor, hypoxia, and other toxic or metabolic factors. Based on the causative factors cerebral edema is differentiated into cytotoxic cerebral edema, vasogenic cerebral edema, osmotic and interstitial cerebral edema. Treatment of cerebral edema depends on timely diagnosis and medical assistance. Pragmatic treatment strategies such as antihypertensive medications, nonsteroidal anti-inflammatory drugs, barbiturates, steroids, glutamate and N-methyl-D-aspartate receptor antagonists and trometamol are used in clinical practice. Although the above mentioned treatment approaches are being used, owing to the complexity of the mechanisms involved in cerebral edema, a single therapeutic strategy which could ameliorate cerebral edema is yet to be identified. However, recent experimental studies have suggested that melatonin, a neurohormone produced by the pineal gland, could be an effective alternative for treating cerebral edema. In animal models of stroke, melatonin was not only shown to reduce cerebral edema but also preserved the blood brain barrier. Melatonin's beneficial effects were attributed to its properties, such as being a potent anti-oxidant, and its ability to cross the blood brain barrier within minutes after its administration. This review summarizes the beneficial effects of melatonin when used for treating cerebral edema.

  14. Pulmonary histopathologic findings, acid-base status, and absorption of colostral immunoglobulins in newborn calves. (United States)

    López, A; Löfstedt, J; Bildfell, R; Horney, B; Burton, S


    A study was conducted to investigate whether aspiration of amniotic fluid is associated with a deleterious effect on absorption of colostral immunoglobulins or on blood gas and acid-base values of healthy newborn calves. Fourteen calves purchased from commercial sources were transported to a research facility immediately after birth and fed colostrum with known concentrations of immunoglobulins. Blood samples for gas analyses were collected within 5 hours of birth, 24 hours later, and prior to euthanasia. Between 3 and 5 days of age, calves were euthanatized by an overdose of barbiturates. Eleven calves had evidence of bronchoaspiration of amniotic fluid, as determined by presence of meconium, squamous epithelium, or keratin in histologic sections of fixed lung or by cytologic analysis of bronchoalveolar lavage fluid. Blood gas tensions and pH were within reference ranges in 11 of 14 calves. Aspiration of amniotic fluid could not be linked to any specific changes in blood gas tensions, acid-base status, or absorption of colostral immunoglobulins. Presence of keratin and meconium in the lungs often was accompanied by mild exudative alveolitis and focal atelectasis. It was concluded that aspiration of small amounts of amniotic fluid with or without meconium is common in calves and is not associated with hypoxemia, respiratory acidosis, or failure of passive transfer.

  15. Steroid hormones and brain development: some guidelines for understanding actions of pseudohormones and other toxic agents

    Energy Technology Data Exchange (ETDEWEB)

    McEwen, B.S.


    Gonadal, adrenal, and thyroid hormones affect the brain directly, and the sensitivity to hormones begins in embryonic life with the appearance of hormone receptor sites in discrete populations of neurons. Because the secretion of hormones is also under control by its neural and pituitary targets, the brain-endocrine axis during development is in a delicately balanced state that can be upset in various ways, and any agent that disrupts normal hormone secretion can upset normal brain development. Moreover, exogenous substances that mimic the actions of natural hormones can also play havoc with CNS development and differentiation. This paper addresses these issues in the following order: First, actions of glucocorticoids on the developing nervous system related to cell division dendritic growth and neurotransmitter phenotype will be presented followed by a discussion of the developmental effects of synthetic steroids. Second, actions of estrogens related to brain sexual differentiation will be described, followed by a discussion of the actions of the nonsteroidal estrogen, diethylstilbestrol, as an example of exogenous estrogenic substances. The most important aspect of the potency of exogenous estrogens appears to be the degree to which they either bypass protective mechanisms or are subject to transformations to more active metabolites. Third, agents that influence hormone levels or otherwise modify the neuroendocrine system, such as nicotine, barbiturates, alcohol, opiates, and tetrahydrocannabinol, will be noted briefly to demonstrate the diversity of toxic agents that can influence neural development and affect personality, cognitive ability, and other aspects of behavior. 53 references.

  16. [Psychoactive substances in biological samples--toxicological laboratory data]. (United States)

    Gomółka, Ewa; Wilimowska, Jolanta; Piekoszewski, Wojciech; Groszek, Barbara


    The subject of the research was the analysis of frequency and type of psychoactive substances used, basing on the determinations the blood and/or urine samples, performed in the toxicological laboratory of the Department of Clinical and Industrial Toxicology Jagiellonian University in Kraków in the period from December 2001 to November 2003. From 17,649 performed determinations--45.5% were positive. 50% of the positive determinations were psychoactive substances. The most often psychoactive substance determined was ethyl alcohol (52.86%), next benzodiazepines (17.41%), amphetamines (10.54%), opiates (8.05%), THC (6.87%), barbiturates (3.74%), and occasionally atropine and cocaine. There was observed a variety of mixed, simultaneously taking psychoactive substances, especially ethyl alcohol, opiates, amphetamine derivatives and cannabinoids. The analysis of the occurrence of psychoactive substances in biological samples from patients treated in different hospital departments, others hospitals and ordered by private persons also was performed. In the last two years 369 private patients ordered psychoactive substances determinations and 78 of them were positive.

  17. Thermal neutron activation analysis of essential and trace elements and organic constituents in Trikatu. An Ayurvedic formulation

    International Nuclear Information System (INIS)

    Choudhury, R.P.; Kumar, A.; Garg, A.N.; Reddy, A.V.R.


    Trikatu, an Ayurvedic formulation of three dried powder spices, ginger, black pepper and pipali in equal proportion is widely used to promote digestion, assimilation and bioavailibility of food. It works synergistically, and hence, is more effective than an equal amount of any of its three ingredients taken separately. Five different brands and its three constituents were analyzed for 31 elements by instrumental neutron activation analysis (INAA) using 5-minute and 6-hour thermal neutron irradiation followed by high-resolution γ-ray spectrometry. Heavy toxic metals Cd, Ni and Pb determined by atomic absorption spectrometry (AAS) were found below permissible limits. Most elements in different brands vary in a narrow range. Ginger is particularly enriched in Ca, Fe, Mg and Mn whereas black pepper is enriched in Cr, Se, P and Zn. Cu/Zn shows linear relationship (r = 0.92) with Cu whereas Fe and Mn exhibit inverse correlation (r = -0.89) in different brands. Hydro distillation of pipali yielded an essential oil whereby 10 organic constituents were identified by GC-MS. Also barbituric and tannic acids were isolated from the aqueous methanolic extract of pipali. (author)

  18. Spectroscopic and Computational Investigations of Ligand Binding to IspH: Discovery of Non-diphosphate Inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    O' Dowd, Bing [Department of Chemistry, University of Illinois, 600 South Mathews Avenue Urbana IL 61801 USA; Williams, Sarah [Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla CA 92093 USA; Wang, Hongxin [Department of Chemistry, University of California, 1 Shields Avenue Davis CA 95616 USA; Lawrence Berkeley National Laboratory, 1 Cyclotron Road Berkeley CA 94720 USA; No, Joo Hwan [Center for Biophysics and Computational Biology, Urbana, IL (United States); Rao, Guodong [Department of Chemistry, University of Illinois, 600 South Mathews Avenue Urbana IL 61801 USA; Wang, Weixue [Center for Biophysics and Computational Biology, Urbana, IL (United States); McCammon, J. Andrew [Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla CA 92093 USA; Howard Hughes Medical Institute, University of California at San Diego, La Jolla CA 92093 USA; National Biomedical Computation Resource, University of California at San Diego, La Jolla CA 92093 USA; Cramer, Stephen P. [Department of Chemistry, University of California, 1 Shields Avenue Davis CA 95616 USA; Lawrence Berkeley National Laboratory, 1 Cyclotron Road Berkeley CA 94720 USA; Oldfield, Eric [Department of Chemistry, University of Illinois, 600 South Mathews Avenue Urbana IL 61801 USA


    Isoprenoid biosynthesis is an important area for anti-infective drug development. One isoprenoid target described is (E)-1-hydroxy-2-methyl-but-2-enyl 4-diphosphate (HMBPP) reductase (IspH), which forms isopentenyl diphosphate and dimethylallyl diphosphate from HMBPP in a 2H + /2e - reduction. IspH contains a 4 Fe-4 S cluster, and in this work, we first investigated how small molecules bound to the cluster by using HYSCORE and NRVS spectroscopies. The results of these, as well as other structural and spectroscopic investigations, led to the conclusion that, in most cases, ligands bound to IspH 4 Fe-4 S clusters by η 1 coordination, forming tetrahedral geometries at the unique fourth Fe, ligand side chains preventing further ligand (e.g., H 2 O, O 2 ) binding. Based on these ideas, we used in silico methods to find drug-like inhibitors that might occupy the HMBPP substrate binding pocket and bind to Fe, leading to the discovery of a barbituric acid analogue with a K i value of ≈500 nm against Pseudomonas aeruginosa IspH.

  19. Choosing an oral contraceptive. (United States)

    Weisberg, E


    This article serves as a summary of the principles of prescription, hormone content, minor side effects, prescriptions for atypical individuals and significant drug interactions for oral contraceptives. There are 5 principles for prescribing oral contraceptives: the lowest possible dose should be given that is effective and produces the least side effects: adequate instructions should be given about the mode of action, taking the medication and possible side effects; adequate instructions about managing missed pills should be given; adequate supervision and explanations should be given if side effects occur; remember that each woman is different and idiosyncratic reactions to different formulations can occur. Possible side effects include: breakthrough bleeding, amenorrhoea, dysmenorrhoea, breast fullness and tenderness, nausea, chloasma, depression, acne, migraines and weight gain. Certain individuals such as epileptics, diabetics, women over 35 and women who have recently given birth need special care. Rifampicin, the phenytoins and barbiturates can all decrease the effectiveness of oral contraceptives. Oral contraceptives may effect the action of anticoagulants, antidiabetic agents and imipramine.

  20. Gene Sequence and Properties of an s-Triazine Ring-Cleavage Enzyme from Pseudomonas sp. Strain NRRLB-12227 (United States)

    Karns, Jeffrey S.


    Pesticides based on the s-triazine ring structure are widely used in cultivation of food crops. Cleavage of the s-triazine ring is an important step in the mineralization of s-triazine compounds and hence in their complete removal from the environment. Cyanuric acid amidohydrolase cleaves cyanuric acid (2,4,6-trihydroxy-s-triazine), which yields carbon dioxide and biuret; the biuret is subject to further metabolism, which yields CO2 and ammonia. The trzD gene encoding cyanuric acid amidohydrolase was cloned into pMMB277 from Pseudomonas sp. strain NRRLB-12227, a strain that is capable of utilizing s-triazines as nitrogen sources. Hydrolysis of cyanuric acid was detected in crude extracts of Escherichia coli containing the cloned gene by monitoring the disappearance of cyanuric acid and the appearance of biuret by high-performance liquid chromatography (HPLC). DEAE and hydrophobic interaction HPLC were used to purify cyanuric acid amidohydrolase to homogeneity, and a spectrophotometric assay for the purified enzyme was developed. The purified enzyme had an apparent Km of 0.05 mM for cyanuric acid at pH 8.0. The enzyme did not cleave any other s-triazine or hydroxypyrimidine compound, although barbituric acid (2,4,6-trihydroxypyrimidine) was found to be a strong competitive inhibitor. Neither the nucleotide sequence of trzD nor the amino acid sequence of the gene product exhibited a significant level of similarity to any known gene or protein. PMID:10427042

  1. Expanding the Cyanuric Acid Hydrolase Protein Family to the Fungal Kingdom (United States)

    Dodge, Anthony G.; Preiner, Chelsea S.


    The known enzymes that open the s-triazine ring, the cyanuric acid hydrolases, have been confined almost exclusively to the kingdom Bacteria and are all homologous members of the rare cyanuric acid hydrolase/barbiturase protein family. In the present study, a filamentous fungus, Sarocladium sp. strain CA, was isolated from soil by enrichment culturing using cyanuric acid as the sole source of nitrogen. A reverse-genetic approach identified a fungal cyanuric acid hydrolase gene composed of two exons and one intron. The translated spliced sequence was 39 to 53% identical to previously characterized bacterial cyanuric acid hydrolases. The sequence was used to generate a gene optimized for expression in Escherichia coli and encoding an N-terminally histidine-tagged protein. The protein was purified by nickel affinity and anion-exchange chromatography. The purified protein was shown by 13C nuclear magnetic resonance (13C-NMR) to produce carboxybiuret as the product, which spontaneously decarboxylated to yield biuret and carbon dioxide. The protein was very narrow in substrate specificity, showing activity only with cyanuric acid and N-methyl cyanuric acid. Barbituric acid was an inhibitor of enzyme activity. Sequence analysis identified genes with introns in other fungi from the Ascomycota that, if spliced, are predicted to encode proteins with cyanuric acid hydrolase activity. The Ascomycota cyanuric acid hydrolase homologs are most closely related to cyanuric acid hydrolases from Actinobacteria. PMID:24039269

  2. Hybrid process for nitrogen oxides reduction

    International Nuclear Information System (INIS)

    Epperly, W.R.; Sprague, B.N.


    This patent describes a process for reducing the nitrogen oxide concentration in the effluent from the combustion of a carbonaceous fuel. It comprises introducing into the effluent a first treatment agent comprising a nitrogenous composition selected from the group consisting of urea, ammonia, hexamethylenetetramine, ammonium salts of organic acids, 5- or 6-membered heterocyclic hydrocarbons having at least one cyclic nitrogen, hydroxy amino hydrocarbons, NH 4 -lignosulfonate, fur-furylamine, tetrahydrofurylamine, hexamethylenediamine, barbituric acid, guanidine, guanidine carbonate, biguanidine, guanylurea sulfate, melamine, dicyandiamide, biuret, 1.1'-azobisformamide, methylol urea, methylol urea-urea condensation product, dimethylol urea, methyl urea, dimethyl urea, calcium cyanamide, and mixtures thereof under conditions effective to reduce the nitrogen oxides concentration and ensure the presence of ammonia in the effluent; introducing into the effluent a second treatment agent comprising an oxygenated hydrocarbon at an effluent temperature of about 500 degrees F. to about 1600 degrees F. under conditions effective to oxidize nitric oxide in the effluent to nitrogen dioxide and ensure the presence of ammonia at a weight ratio of ammonia to nitrogen dioxide of about 1:5 to about 5:1; and contacting the effluent with an aqueous scrubbing solution having a pH of 12 or lower under conditions effective to cause nitrogen dioxide to be absorbed therein

  3. [40 years of toxicomania at the psychiatric hospital in Liège]. (United States)

    Husquinet, H


    Drug abuse was observed during 40 years (1939-1979) in a psychiatric hospital for women (sanatorium Sainte-Agathe, Liège, Belgium). Seventy patients were labelled with that diagnosis, -i.e. 2,9% of 2386 admissions. The frequency of drug addiction grew with years and between 1975 and 1979, outnumbered 10% of all admissions. 3/4 of those patients were previously inmates of other psychiatric clinics and well known in medical urgency services. Morphinomaniacs were the only patients between 1939 and 1949 (11 women). As a rule, they survived and did not come back. No haschich, L.S.D. or heroin addicts were seen: their psychiatric confinement was never required. Beginning in december 1959, barbituromaniacs (58 patients) invaded the wards. Other hypnotics were used as well (e.g. metaqualone). Forty-five per cent of the patients died and the survivors came back and back again, -en masse. The illness is very serious if it starts before 30 years: the risk of death goes to 75%. Barmaids and prostitutes were definitely doing hazardous jobs (5 deaths among 6 cases). Other psychiatric illnesses interfere with toxicomania, especially depression. Four patients committed suicide without hypnotics. To conclude: barbiturates are dangerous drugs and they ought not to be used for insomnia. Benzodiazepine abuse did not occur in the hospital and did not induce fatal issues. Combined with phenothiazines, benzodiazepines can solve nearly all sleep disturbances.

  4. Therapeutic approaches to cerebral vasospasm complicating ruptured aneurysm

    Directory of Open Access Journals (Sweden)

    Mohamed Barbarawi


    Full Text Available Cerebral vasospasm is a serious complication of ruptured aneurysm. In order to avoid short- and long-term effects of cerebral vasospasm, and as there is no single or optimal treatment modality employed, we have instituted a protocol for the prevention and treatment of vasospasm in patients suffering aneurysmal sub-arachnoid hemorrhage (SAH. We then reviewed the effectiveness of this protocol in reducing the mortality and morbidity rate in our institution. In this study we present a retrospective analysis of 52 cases. Between March 2004 and December 2008 52 patients were admitted to our service with aneurysmal SAH. All patients commenced nimodipine, magnesium sulphate (MgSO4 and triple H therapy. Patients with significant reduction in conscious level were intubated, ventilated and sedated. Intracranial pressure (ICP monitoring was used for intubated patients. Sodium thiopental coma was induced for patients with refractory high ICP; angiography was performed for diagnosis and treatment. Balloon angioplasty was performed if considered necessary. Using this protocol, only 13 patients (25% developed clinical vaso-spasm. Ten of them were given barbiturates to induce coma. Three patients underwent transluminal balloon angioplasty. Four out of 52 patients (7.7% died from severe vasospasm, 3 patients (5.8% became severely disabled, and 39 patients (75% were discharged in a condition considered as either normal or near to their pre-hemorrhage status. Our results confirm that the aforementioned protocol for treatment of cerebral vasospasm is effective and can be used safely.

  5. Burst Suppression for ICP Control. (United States)

    Zeiler, Frederick A; Akoth, Eva; Gillman, Lawrence M; West, Michael


    The goal of our study was to perform a systematic review of the literature to determine the effect that burst suppression has on intracranial pressure (ICP) control. All articles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to January 2015), reference lists of relevant articles, and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and the Grading of Recommendation Assessment Development and Education (GRADE) methodology. Seven articles were considered for review. A total of 108 patients were studied, all receiving burst suppression therapy. Two studies failed to document a decrease in ICP with burst suppression therapy. There were reports of severe hypotension and increased infection rates with barbiturate-based therapy. Etomidate-based suppressive therapy was linked to severe renal dysfunction. There currently exists both Oxford level 2b and GRADE C evidence to support that achieving burst suppression reduces ICP, and also has no effect on ICP, in severe traumatic brain injury. The literature suggests burst suppression therapy may be useful for ICP reduction in certain cases, although these situations are currently unclear. In addition, the impact on patient functional outcome is unclear. Further prospective study is warranted.

  6. Intracranial pressure monitoring after primary decompressive craniectomy in traumatic brain injury: a clinical study. (United States)

    Picetti, Edoardo; Caspani, Maria Luisa; Iaccarino, Corrado; Pastorello, Giulia; Salsi, Pierpaolo; Viaroli, Edoardo; Servadei, Franco


    Intracranial pressure (ICP) monitoring represents an important tool in the management of traumatic brain injury (TBI). Although current information exists regarding ICP monitoring in secondary decompressive craniectomy (DC), little is known after primary DC following emergency hematoma evacuation. Retrospective analysis of prospectively collected data. Inclusion criteria were age ≥18 years and admission to the intensive care unit (ICU) for TBI and ICP monitoring after primary DC. Exclusion criteria were ICU length of stay (LOS) pressure (CPP) after primary DC, (2) to evaluate the relationship between ICP/CPP and neurological outcome and (3) to characterize and evaluate ICP-driven therapies after DC. A total of 34 patients were enrolled. Over 308 days of ICP/CPP monitoring, 130 days with at least one episode of intracranial hypertension (26 patients, 76.5%) and 57 days with at least one episode of CPP intracranial hypertension was treated with: barbiturate coma (n = 7, 20.6%), external ventricular drain (EVD) (n = 4, 11.8%), DC diameter widening (n = 1, 2.9%) and removal of newly formed hematomas (n = 3, 8.8%). Intracranial hypertension and/or low CPP occurs frequently after primary DC; their occurence is associated with an unfavorable neurological outcome. ICP monitoring appears useful in guiding therapy after primary DC.

  7. Role of Intracranial Pressure Monitoring in Management of Patients with Severe Traumatic Brain Injury: Results of a Large Level I Trauma Center in Southern Iran. (United States)

    Khalili, Hosseinali; Sadraei, Nazanin; Niakan, Amin; Ghaffarpasand, Fariborz; Sadraei, Amin


    To determine the role of intracranial pressure (ICP) monitoring in management of patients with severe traumatic brain injury (TBI) admitted to a large level I trauma center in Southern Iran. This was a cohort study performed during a 2-year period in a level I trauma center in Southern Iran including all adult patients (>16 years) with severe TBI (Glasgow Coma Scale [GCS] score, 3-8) who underwent ICP monitoring through ventriculostomy. The management was based on the recorded ICP values with threshold of 20 mm Hg. Decompressive craniectomy was performed in patients with intractable intracranial hypertension (persistent ICP ≥25 mm Hg). In unresponsive patients, barbiturate coma was induced. Patients were followed for 6 months and Glasgow Outcome Scale Extended was recorded. The determinants of favorable and unfavorable outcome were also determined. Overall, we included 248 patients with mean age of 34.6 ± 16.6 years, among whom there were 216 men (87.1%) and 32 women (12.9%). Eighty-five patients (34.2%) had favorable and 163 (65.8%) unfavorable outcomes. Those with favorable outcome had significantly lower age (P = 0.004), higher GCS score on admission (P intracranial hypertension (P intracranial hypertension, and maximum recorded ICP are important determinants of outcome in patients with severe TBI. ICP monitoring assisted us in targeted therapy and management of patients with severe TBI. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Relationship between the matrix effect and the physicochemical properties of analytes in gas chromatography. (United States)

    Saka, Kanju; Kudo, Keiko; Hayashida, Makiko; Kurisaki, Emiko; Niitsu, Hisae; Terada, Masaru; Yamaguchi, Koji; Yoshida, Ken-ichi


    The phenomenon "matrix-induced chromatographic response enhancement" (matrix effect) causes quantitative errors in gas chromatography (GC) analyses. This effect varies according to the analyte nature, matrix type and concentration, and GC-system parameters. By focusing on the physicochemical properties of analytes, a predictive model was developed for the matrix effect using quantitative structure-property relationships. Experimental values of the matrix effect were determined for 58 compounds in a serum extract obtained from solid-phase extraction as the matrix. Eight molecular descriptors were selected, and the matrix-effect model was developed by multiple linear regression. The developed model predicted values for the matrix effect without any further experimental measurements. It also indicated that the molecular polarity (particularly H-bond donors) and volume of the analyte increase the matrix effect, while hydrophobicity and increasing number of nonpolar carbon atoms in the analyte decrease the matrix effect. The model was applied to the analysis of barbiturates. The predicted values indicated that N-methylation decreases the matrix effect, and the relative predicted values were effective for the selection of an internal standard. The obtained insight into the matrix effect and the prediction data will be helpful for developing quantitative analysis strategies.

  9. Actions of insecticides on the insect GABA receptor complex

    International Nuclear Information System (INIS)

    Bermudez, I.; Hawkins, C.A.; Taylor, A.M.; Beadle, D.J.


    The actions of insecticides on the insect gamma-aminobutyric acid (GABA) receptor were investigated using [35S]t-butylbicyclophosphorothionate [( 35S]TBPS) binding and voltage-clamp techniques. Specific binding of [35S]TBPS to a membrane homogenate derived from the brain of Locusta migratoria locusts is characterised by a Kd value of 79.3 ± 2.9 nM and a Bmax value of 1770 ± 40 fmol/mg protein. [35S]TBPS binding is inhibited by mM concentrations of barbiturates and benzodiazepines. In contrast dieldrin, ivermectin, lindane, picrotoxin and TBPS are inhibitors of [35S]TBPS binding at the nanomolar range. Bicuculline, baclofen and pyrethroid insecticides have no effect on [35S]TBPS binding. These results are similar to those obtained in electrophysiological studies of the current elicited by GABA in both Locusta and Periplaneta americana central neurones. Noise analysis of the effects of lindane, TBPS, dieldrin and picrotoxin on the cockroach GABA responses reveals that these compounds decrease the variance of the GABA-induced current but have no effect on its mean open time. All these compounds, with the exception of dieldrin, significantly decrease the conductance of GABA-evoked single current

  10. Isotopically labelled pyrimidines and purines

    International Nuclear Information System (INIS)

    Balaban, A.T.; Bally, I.


    Among the three diazines, pyrimidine is by far the most important one because its derivatives uracil, thymine and cytosine are constituents of the ubiquitous deoxynucleic acids (DNA) and ribonucleic acids (RNA). Other derivatives of pyrimidine without condensed rings include barbiturates, alloxan, orotic acid and thiamine or vitamin B 1 . From the polycyclic derivatives of pyrimidine such as pteridine, alloxazine, and purine, the latter, through its derivatives adenine and guanine complete the list of bases which occur in DNA and RNA: in addition, other purine derivatives such as hypoxanthine, xanthine, theobromine, theophylline, caffeine and uric acid are important natural products with biological activity. The paper presents methods for preparing isotopically labeled pyrimidines as well as purine derivatives. For convenience, the authors describe separately carbon-labeled with radioisotopes 11 C (T 1/2 = 20.3 min) and 14 C (T 1/2 = 5736 years) or the stable isotope 13 C (natural abundance 1.1%) and then hydrogen-labeled systems with the radioisotope 3 H ≡ T (T 1/2 = 12.346 years) or with the stable isotope 2 H ≡ D (natural abundance 0.015%). We do not separate stable from radioactive isotopes because the synthetic methods are identical for the same element; however, the introduction of hydrogen isotopes into organic molecules is often performed by reactions such as isotope exchange which cannot take place in the case of carbon isotopes

  11. Chemical speciation and equilibria of some nucleic acid compounds and their iron(III) complexes (United States)

    Masoud, Mamdouh S.; Abd El-Kaway, Marwa Y.; Hindawy, Ahmed M.; Soayed, Amina A.

    The pH effect on electronic absorption spectra of some biologically active nucleic acid constituents have been studied at room temperature and the mechanism of ionization was explained. These compounds are of two categories (pyrimidines: [barbital; 5,5'-diethyl-barbituric acid], [SBA; 4,6-dihydroxy-2-mercapto-pyrimidin], [NBA; 5-nitro-2,4,6(1H,3H,5H)-pyrimidine trione] and [TU; 2,3-dihydro-2-thioxo-pyrimidin-4(1H)-one]) and (purines: [adenine; 6-amino purine], its [Schiff bases derived from adenine-acetylacetone; (Z)-4-(7H-purin-6-ylimino)pentan-2-one) and adenine-salicylaldehyde; 2-((7H-purin-6-ylimino) methyl) phenol] and its [Azo derived from adenine-resorcinol; 4-((7H-purin-6-yl)-diazenyl) benzene-1,3-diol]. The phenomena of tautomerization assigned different tautomers. Different spectrophotometric methods are applied to evaluate the pK's values that explained with their molecular structures. The interaction of Fe3+ with some selected pyrimidines (barbital, NBA and SBA) was explained using familiar six spectrophotometric methods. The data typified the existence of different absorbing species with the different stoichiometries 1:1, 1:2, 1:3 and 2:3. The stability constant of the complexes was computed. More approach was deduced to assign the existence of different species applying the distribution diagrams.

  12. Psychedelic drugs, hippie counterculture, speed and phenobarbital treatment of sedative-hypnotic dependence: a journey to the Haight Ashbury in the Sixties. (United States)

    Wesson, Donald R


    The 1960s were a time of social upheaval, wars, vibrant creativity and missed opportunity. Mainstream culture and a psychedelic drug-using counterculture shared a belief in "better living through chemistry'," but they disagreed about the particular chemistry. The Vietnam war and the cold war with the Soviet Union, racial discrimination, and gender roles fueled political activism. "Yes we can" was not a slogan of the time but political activists clearly believed they could change the beliefs, attitudes and behavior of mainstream culture; and they did. Hippie counterculture on the other hand was largely alienated and strove primarily to develop a separate culture with its own mores, beliefs and lifestyles. Although there was some overlap between hippies and activists, hippies didn't generally have the same sense of political empowerment. Hippie enclaves developed in New York; Boston; Seattle; Austin, Texas and elsewhere; but the epicenter was arguably the Haight-Asbury District of San Francisco. Psychedelic drugs, marijuana and the Vietnam war were among many wedge issues. This paper conjures up a personal history related to the evolution of the hippie counterculture, changing drug use patterns in the Haight-Ashbury, and the origins of a technique of withdrawing patients from barbiturates and other sedative-hypnotics using phenobarbital variously known as the "Phenobarbital Withdrawal Protocol, or the "Smith and Wesson Protocol."

  13. [Present status and future of hypnotic drug treatment for insomnia]. (United States)

    Uchiyama, Makoto; Konno, Michiko


    Pharmacological treatments of insomnia have become safer since the first benzodiazepine receptor agonist (BzRA) hypnotic was introduced in the 1960's. Though BzRAs could hardly cause a fatal condition even in cases of overdosing, they had inherited the arguments on addiction and withdrawal from the prior studies of barbiturate hypnotics that indicated they are strongly addictive. In the 2000s, it was repeatedly demonstrated that insomnia as well as sleep deprivation underlie the development and deterioration of comorbid diseases such as hypertension, cardiovascular diseases, diabetes and depression, and that the proper use of hypnotic drugs is unlikely to cause tolerance, addiction nor rebound phenomena, but likely to be associated with improvement of QOL. Thus, the 2005's consensus report on chronic insomnia by NIH has recommended general physicians to facilitate insomnia treatment to prevent the development of physical and/or mental disorders. The author reviewed in this article the efficacy and side effects of BzRA hypnotics, a hypnotic drug therapy combined with cognitive and behavioral interventions, uses of melatonin receptor agonist in general and sleep medicine practices, and future utilization of newly-developed orexin antagonists for insomnia treatment.

  14. Comparison of umbilical cord tissue and meconium for the confirmation of in utero drug exposure. (United States)

    Colby, Jennifer M


    Drug screening in neonates is traditionally performed using meconium, but cord tissue has been proposed as an alternative specimen. This study compares the detection of drugs in a large number of paired meconium and umbilical cord tissue samples from subjects at risk of in utero drug exposure. Physician-ordered toxicology results and clinical information were collected in a retrospective review of subject medical records. All toxicology testing was performed by a national reference laboratory using a combination of immunoassays and chromatography-mass spectrometry. The comparison was limited to drugs present in both cord and meconium panels. Overall agreement between cord and meconium ranged from 76% (cannabinoids) to 100% (barbiturates), but Cohen's kappa was umbilical cord tissue and meconium. For the drugs studied here, meconium provides greater sensitivity, and is likely to remain the specimen of choice when sensitivity is of greatest importance. These results can help clinicians, laboratorians, and epidemiologists to (1) select the most appropriate test to confirm a suspected drug exposure and (2) interpret discordant results when testing is performed in multiple matrices. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  15. Medical treatment of neuro diseases of dogs and cats / Fármacos utilizados no tratamento das afecções neurológicas de cães e gatos

    Directory of Open Access Journals (Sweden)

    Ronaldo Cassimiro da Costa


    Full Text Available A revision of the current literature regarding medical management of neurological diseases of dogs and cats is presented. The indications, doses, and duration of the recommended treatment of several medications are reviewed. The authors have reviewed analgesic, antibiotic, anticonvulsants, barbiturates, anticolinesterasics, antifungals, antifibrinolytics, steroidal and non-steroidal antiinflammatory, antineoplastics, antipsychotics, anxiolytics, antidepressants, free radical scavengers, diuretics, drugs used in the treatment of micturition disorders, phytotherapeutics, nutraceuticals, muscle relaxant and vitamins.Este trabalho compreende uma revisão da literatura, dos diferentes fármacos utilizados na terapêutica das afecções neurológicas de cães e gatos, assim como sua indicação, dosagens, e duração do tratamento. Nesse contexto incluíram-se analgésicos, antibióticos, anticonvulsivantes, barbitúricos, anticolinesterásicos, antifúngicos, antifibrinolíticos, antiinflamatórios esteróides e não esteróides, antineoplásicos, antipsicóticos, ansiolíticos, antidepressivos, antioxidantes e varredores de radicais livres, diuréticos, fármacos utilizados nos distúrbios da micção, fitoterápicos, modificadores do metabolismo articular (nutracêuticos, relaxantes musculares e vitaminas.

  16. A study of elderly unnatural deaths in medico-legal autopsies at Lucknow locality. (United States)

    Kumar, S; Verma, A K


    The main aim of this study was to determine the causes and epidemiological aspects of unnatural deaths in the elderly. Data were collected on 4405 male and female victims of unnatural deaths aged 50 years or more from the total number of 21,235 autopsies performed in King George's Medical University, Lucknow, India over a 5-year period, from 2008 to 2012. There were 3165 male victims and 1240 female victims. Unnatural deaths were higher in rural (64%) than in urban (37%) areas. Accidental deaths were the most common manner of unnatural deaths (59%), followed by suicidal deaths (34%) and homicidal deaths (7%). Traumas were the most common cause of unnatural death (77.3%), followed by undetermined causes (16.6%) and toxicological causes (6.1%). The most common causes of traumatic deaths were blunt head injuries (34%) followed by stab in the chest (6%), burn (16%), blunt injuries in abdomen and chest (10%), firearm injuries in the head and trunk (9%), strangulation (3%), stab in the abdomen (4%), smothering (4%), cut throat (3%), throttling (1%) and hanging (10%). Carbamate poisoning was the most common cause of toxicological deaths (44%) followed by organophosphorous poisoning (33%), ethyl alcohol poisoning (12%), barbiturate poisoning (3%) and zinc phosphide poisoning (8%).

  17. Synthesis and PASS-assisted in silico approach of some novel 2-substituted benzimidazole bearing a pyrimidine-2, 4, 6(trione system as mucomembranous protector

    Directory of Open Access Journals (Sweden)

    Bijo Mathew


    Full Text Available Purpose: The present paper demonstrates the utility of PASS computer-aided program and makes a clear comparison of predicted and observed pharmacological properties of some novel 5-[(2E-1-(1H-benzimidazol-2-yl-3-substituted phenylprop-2-en-1-ylidene] pyrimidine-2, 4, 6 (1H, 3H, 5H-triones (5a-f. Materials and Methods: The synthesis of the titled derivatives were achieved by the reaction between 2E-1-(1H-benzimidazol-2-yl-3-phenylprop-2-en-1-ones (4a-f and barbituric acid in the presence of catalytic amount of acetic acid medium. All the final structures were assigned on the basis of IR, 1 HNMR and mass spectra analysis. All the newly synthesized compounds were screened for their antiulcer activity in the pylorus-ligated rats. Results: Compounds 5b, 5e and 5c showed a percentage protection of (69.58, 69.56 and 67.17 at a dose of 50 mg/kg b.w. when compared to standard omeprazole (77.37%, 2 mg/kg b.w.. Conclusion: Scanning of stomach specimens using electron microscope revealed that the mice treated with standard and synthetic derivatives had no injury observed in stomach mucosa, which is identical to that of the control animal.

  18. Electrophysiologic studies of cutaneous nerves of the forelimb of the cat. (United States)

    Kitchell, R L; Canton, D D; Johnson, R D; Maxwell, S A


    The cutaneous innervation of the forelimb was investigated in 20 barbiturate-anesthetized cats by using electrophysiological techniques. The cutaneous area (CA) innervated by each cutaneous nerve was delineated in at least six cats by brushing the hair in the CA with a small watercolor brush while recording from the nerve. Mapping of adjacent CA revealed larger overlap zones (OZ) than were noted in the dog. Remarkable findings were that the brachiocephalic nerve arose from the axillary nerve and the CA comparable to that supplied by the cutaneous branch of the brachiocephalic nerve in the dog was supplied by a cutaneous branch of the suprascapular nerve. The CA supplied by the communicating branch from the musculocutaneous to the median nerve was similar in both species except that the communicating branch arose proximal to any other branches of the musculocutaneous nerve in the cat, whereas it was a terminal branch in the dog. The superficial branch of the radial nerve gave off cutaneous brachial branches in the cat proximal to the lateral cutaneous antebrachial nerve. The CA of the palmar branches of the ulnar nerve did not completely overlap the CA of the palmar branches of the median nerve as occurred in the dog; thus an autonomous zone (AZ) for the CA of the palmar branches of the median nerve is present in the cat, whereas no AZ existed for the CA of this nerve in the dog.

  19. Electrophysiologic studies of cutaneous nerves of the thoracic limb of the dog. (United States)

    Kitchell, R L; Whalen, L R; Bailey, C S; Lohse, C L


    The cutaneous innervation of the thoracic limb was investigated in 36 barbiturate-anesthetized dogs, using electrophysiologic techniques. The cutaneous area (CA) innervated by each cutaneous nerve was delineated in at least five dogs by stroking the hair in the area with a small watercolor brush while recording from the nerve. Mapping of adjacent CA revealed areas of considerable overlapping. The part of the CA of a given nerve supplied by only that nerve is referred to as its autonomous zone. Of all nerves arising from the brachial plexus, only the suprascapular, subscapular, lateral thoracic, thoracodorsal, and cranial and caudal pectoral nerves lacked cutaneous afferents. The dorsal cutaneous branch of C6 had a CA, but no grossly demonstrable dorsal cutaneous branches for C7 C8, or T1 were found. The cervical nerves had ventral cutaneous branches, but no lateral cutaneous branches. Thoracic nerves T2-T4 had dorsal, ventral, and lateral cutaneous branches. The cutaneous branches of the brachiocephalic, axillary, musculocutaneous, radial, median, and ulnar nerves all had CA which were overlapped by adjacent CA, thus their autonomous zones were much smaller than the cutaneous areas usually depicted for these nerves in anatomy and neurology textbooks.

  20. Deep thiopental anesthesia alters steady-state glucose homeostasis but not the neurochemical profile of rat cortex. (United States)

    Lei, Hongxia; Duarte, Joao M N; Mlynarik, Vladimir; Python, Agathe; Gruetter, Rolf


    Barbiturates are regularly used as an anesthetic for animal experimentation and clinical procedures and are frequently provided with solubilizing compounds, such as ethanol and propylene glycol, which have been reported to affect brain function and, in the case of (1)H NMR experiments, originate undesired resonances in spectra affecting the quantification. As an alternative, thiopental can be administrated without any solubilizing agents. The aim of the study was to investigate the effect of deep thiopental anesthesia on the neurochemical profile consisting of 19 metabolites and on glucose transport kinetics in vivo in rat cortex compared with alpha-chloralose using localized (1)H NMR spectroscopy. Thiopental was devoid of effects on the neurochemical profile, except for the elevated glucose at a given plasma glucose level resulting from thiopental-induced depression of glucose consumption at isoelectrical condition. Over the entire range of plasma glucose levels, steady-state glucose concentrations were increased on average by 48% +/- 8%, implying that an effect of deep thiopental anesthesia on the transport rate relative to cerebral glucose consumption ratio was increased by 47% +/- 8% compared with light alpha-chloralose-anesthetized rats. We conclude that the thiopental-induced isoelectrical condition in rat cortex significantly affected glucose contents by depressing brain metabolism, which remained substantial at isoelectricity. 2009 Wiley-Liss, Inc.

  1. Comparison of meconium and neonatal hair analysis for detection of gestational exposure to drugs of abuse. (United States)

    Bar-Oz, B; Klein, J; Karaskov, T; Koren, G


    Meconium and hair are two biological markers of in utero exposure to illicit drugs. To compare the sensitivity of the two tests for different drugs. Motherisk laboratory which tests in utero drug exposure in Toronto. Cocaine, benzoylecgonine, opiates, cannabis, benzodiazepines, methadone, and barbiturates were measured in pairs of hair and meconium samples from the same neonates. Meconium was marginally more sensitive than neonatal hair for detection of cocaine and cannabis, possibly because it may detect second trimester exposure whereas hair grows only during the third trimester of pregnancy. There was a significant correlation between hair and meconium concentrations of cocaine, cannabis, and opiates. In cases of clinical suspicion and a negative neonatal urine test, both meconium and hair are effective biological markers of in utero illicit drug exposure. Meconium may be more sensitive, but neonatal hair is available for three months whereas meconium is available for only one or two days. In contrast, the use of meconium, being a discarded material, is more acceptable to some parents than hair testing, which entails cutting scalp hair from the newborn.

  2. [Prevalence of human immunodeficiency virus infection and behaviors associated with its transmission among parenteral drug users selected on the street]. (United States)

    Rodés, A; Vall, M; Casabona, J; Nuez, M; Rabella, N; Mitrani, L


    To estimate the prevalence of HIV infection and the associated risk behaviours among intravenous drug users not receiving treatment for their drug dependence. A cross-sectional study of 200 intravenous drug users recruited from the streets of Barcelona in 1993. Information about the socio-demographic aspects and behaviours was obtained through a personal interview using a standardised questionnaire which was carried out by three ex-drug users. Saliva samples were used to determine anti HIV antibodies. The prevalence of HIV infection was 51%. 57% borrowed used syringes, 65% lended their syringes, and 41% practised back of frontloading. 85% if those who shared syringes always cleaned them, however 59% only used water. 78% had heterosexual relations, in 33% of the cases with a non-injecting sexual partner. 65% always used condoms with sexual clients although only 26% always used them with stable sexual partners and 36% with casual sexual partners. 78% had performed the HIV test and among those who knew they were seropositive, 40% had received some kind of health control in the last 6 months. Not having a legal income, injecting speedball or barbiturates, unknowing self HIV negative status and practicing forms of indirect sharing were found to be independently associated with syringe sharing. The high prevalence of HIV infection and associated risk behaviours highlights the need to increase and adapt the prevention efforts and investigation to this group. Social marginalization and poliuse of drugs should be addressed in HIV prevention programs.

  3. Fast targeted analysis of 132 acidic and neutral drugs and poisons in whole blood using LC-MS/MS. (United States)

    Di Rago, Matthew; Saar, Eva; Rodda, Luke N; Turfus, Sophie; Kotsos, Alex; Gerostamoulos, Dimitri; Drummer, Olaf H


    The aim of this study was to develop an LC-MS/MS based screening technique that covers a broad range of acidic and neutral drugs and poisons by combining a small sample volume and efficient extraction technique with simple automated data processing. After protein precipitation of 100μL of whole blood, 132 common acidic and neutral drugs and poisons including non-steroidal anti-inflammatory drugs, barbiturates, anticonvulsants, antidiabetics, muscle relaxants, diuretics and superwarfarin rodenticides (47 quantitated, 85 reported as detected) were separated using a Shimadzu Prominence HPLC system with a C18 separation column (Kinetex XB-C18, 4.6mm×150mm, 5μm), using gradient elution with a mobile phase of 25mM ammonium acetate buffer (pH 7.5)/acetonitrile. The drugs were detected using an ABSciex(®) API 2000 LC-MS/MS system (ESI+ and -, MRM mode, two transitions per analyte). The method was fully validated in accordance with international guidelines. Quantification data obtained using one-point calibration compared favorably to that using multiple calibrants. The presented LC-MS/MS assay has proven to be applicable for determination of the analytes in blood. The fast and reliable extraction method combined with automated processing gives the opportunity for high throughput and fast turnaround times for forensic and clinical toxicology. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Legacy of a Chemical Factory Site: Contaminated Groundwater Impacts Stream Macroinvertebrates. (United States)

    Rasmussen, Jes J; McKnight, Ursula S; Sonne, Anne Th; Wiberg-Larsen, Peter; Bjerg, Poul L


    Legislative and managing entities of EU member states face a comprehensive task because the chemical and ecological impacts of contaminated sites on surface waters must be assessed. The ecological assessment is further complicated by the low availability or, in some cases, absence of ecotoxicity data for many of the compounds occurring at contaminated sites. We studied the potential impact of a contaminated site, characterised by chlorinated solvents, sulfonamides, and barbiturates, on benthic macroinvertebrates in a receiving stream. Most of these compounds are characterised by low or unknown ecotoxicity, but they are continuously discharged into the stream by way of a long-lasting source generating long-term chronic exposure of the stream biota. Our results show that taxonomical density and diversity of especially sediment dwelling taxa were reduced by >50 % at the sampling sites situated in the primary inflow zone of the contaminated GW. Moreover, macroinvertebrate communities at these sampling sites could be distinguished from those at upstream control sites and sites situated along a downstream dilution gradient using multidimensional scaling. Importantly, macroinvertebrate indices currently used did not identify this impairment, thus underpinning an urgent need for developing suitable tools for the assessment of ecological effects of contaminated sites in streams.

  5. 2-Methylpyridinium/pyridinium 5-(2,4-dinitrophenyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olates as potent anticonvulsant agents—synthesis and crystal structure (United States)

    Mangaiyarkarasi, G.; Kalaivani, D.


    The molecular salt, 2-methylpyridinium 5-(2,4-dinitrophenyl)-2,6-dioxo-1,2,3,6-tetrahydropy-rimidin-4-olate) ( I), is prepared from the ethanolic solution of 1-chloro-2,4-dinitrobenzene, pyrimidine-2,4,6-(1H,3H,5H)-trione (barbituric acid) and 2-methylpyridine at room temperature, and the molecular salt, pyridinium 5-(2,4-dinitrophenyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate ( II), is prepared from the same reactants, by dissolving them in hot DMSO and ethanol mixture at 70°C. The structures of I and II are characterized by visible, IR, 1H-NMR, 13C-NMR and elemental analysis and confirmed by single crystal X-ray analysis. Both the salts crystallize in triclinic crystal system with sp. gr. . They possess noticeable anticonvulsant activity even at low concentration (25 mg/kg). Acute toxicity studies of these complexes indicate that LD50 values are greater than 1500 mg/kg and the tested animals do not show any behavioural changes.

  6. Pharmacological therapy for analgesia and sedation in the newborn. (United States)

    Anand, K J S; Hall, R W


    Rapid advances have been made in the use of pharmacological analgesia and sedation for newborns requiring neonatal intensive care. Practical considerations for the use of systemic analgesics (opioids, non-steroidal anti-inflammatory agents, other drugs), local and topical anaesthetics, and sedative or anaesthetic agents (benzodiazepines, barbiturates, other drugs) are summarised using an evidence-based medicine approach, while avoiding mention of the underlying basic physiology or pharmacology. These developments have inspired more humane approaches to neonatal intensive care. Despite these advances, little is known about the clinical effectiveness, immediate toxicity, effects on special patient populations, or long-term effects after neonatal exposure to analgesics or sedatives. The desired or adverse effects of drug combinations, interactions with non-pharmacological interventions or use for specific conditions also remain unknown. Despite the huge gaps in our knowledge, preliminary evidence for the use of neonatal analgesia and sedation is available, but must be combined with a clear definition of clinical goals, continuous physiological monitoring, evaluation of side effects or tolerance, and consideration of long-term clinical outcomes.


    Directory of Open Access Journals (Sweden)

    Stevan Glogovac


    Full Text Available Humans have a long hystory of stimulating and mind-altering substances use. Depressive drugs, including morphine and other narcotics, barbiturates and ethanol, are strongly addictive for susceptible individuals. The phenomenon is most striking in the case of opiates. Morphine is an alkaloid of opium. Named after the Roman god of dreams, Morpheus, the compound has potent analgesic properties toward all types of pain. By supstitution of two hydroxylic groups of morphine many natural and semysyntetic derivatives with different pharmacological activity and analgesic action are obtained. Determinations and quantifications of narcotic analgesics in drug addicts are important in forensic medicine and clinical toxicology. With development of highly sensitive chromatography technique (HPLC-GC, GH-MS, more and more substances are determined, including opioid drugs: morphine, codeine, dyhydrocodeine, and heroin and 6-monoacetyl morphine. Hair analysys by HPLC/MS spectroscopy is an effective forensic tool for determining the use of abused drugs. The “fingerprint” for heroin in the mixture with the other substances(1-10 components is determined by 1D-TOCSY NMR.

  8. Refractory High Intracranial Pressure following Intraventricular Hemorrhage due to Moyamoya Disease in a Pregnant Caucasian Woman

    Directory of Open Access Journals (Sweden)

    Virginie Montiel


    Full Text Available Intraventricular hemorrhage during pregnancy is usually followed by a poor recovery. When caused by moyamoya disease, ischemic or hemorrhagic episodes may complicate the management of high intracranial pressure. A 26-year-old Caucasian woman presented with generalized seizures and a Glasgow Coma Score (GCS of 3 during the 36th week of pregnancy. The fetus was delivered by caesarean section. The brain CT in the mother revealed bilateral intraventricular hemorrhage, a callosal hematoma, hydrocephalus and right frontal ischemia. Refractory high intracranial pressure developed and required bilateral ventricular drainage and intensive care treatment with barbiturates and hypothermia. Magnetic resonance imaging and cerebral angiography revealed a moyamoya syndrome with rupture of the abnormal collateral vascular network as the cause of the hemorrhage. Intracranial pressure could only be controlled after the surgical removal of the clots after a large opening of the right ventricle. Despite an initially low GCS, this patient made a good functional recovery at one year follow-up. Management of refractory high intracranial pressure following moyamoya related intraventricular bleeding should require optimal removal of ventricular clots and appropriate control of cerebral hemodynamics to avoid ischemic or hemorrhagic complications.

  9. Radiation dosimetry of 15O-labeled O2, CO2 and CO gases administered continuously in the breath

    International Nuclear Information System (INIS)

    Bigler, R.E.; Sgouros, G.


    The ratio of activity per liter of air supplied to the activity concentration in the blood for oxygen-15 labeled carbon dioxide and carbon monoxide was found to show an approximate factor of 10 variation from study to study in dog experiments (Bigler and co-workers, unpublished data). Unless human measurement experience shows the lung extraction efficiency to be more constant and therefore predictable, radiation dose estimates should be empirically verified in each study by a rapid and early measurement of the exhaled and unused gas activities. Patient activity extraction would be obtained by difference of this measurement with the supplied activity. The results show calculations for a factor of 2 lower and higher than the extraction efficiency observed for barbiturate sedated dogs. The total-body cumulated activities can be converted into effective total administered doses by multiplying them by the decay constant for oxygen-15 (20.453 hr -1 ). This gives for O 2 , CO 2 and CO, respectively, 227, 98 and 95 mCi/hr or 3.79, 1.64 and 1.58 mCi/min. Assuming the patient inhales 7.4 liters/min., the extraction efficiencies from the 1 mCi/liter-air supplied to the patient amounts to for O 2 , CO 2 and CO, respectively 51, 22 and 21%

  10. At clinically relevant concentrations the anaesthetic/amnesic thiopental but not the anticonvulsant phenobarbital interferes with hippocampal sharp wave-ripple complexes

    Directory of Open Access Journals (Sweden)

    Sotiriou Evangelos


    Full Text Available Abstract Background Many sedative agents, including anesthetics, produce explicit memory impairment by largely unknown mechanisms. Sharp-wave ripple (SPW-R complexes are network activity thought to represent the neuronal substrate for information transfer from the hippocampal to neocortical circuits, contributing to the explicit memory consolidation. In this study we examined and compared the actions of two barbiturates with distinct amnesic actions, the general anesthetic thiopental and the anticonvulsant phenobarbital, on in vitro SPW-R activity. Results Using an in vitro model of SPW-R activity we found that thiopental (50–200 μM significantly and concentration-dependently reduced the incidence of SPW-R events (it increased the inter-event period by 70–430 %. At the concentration of 25 μM, which clinically produces mild sedation and explicit memory impairment, thiopental significantly reduced the quantity of ripple oscillation (it reduced the number of ripples and the duration of ripple episodes by 20 ± 5%, n = 12, P P P Conclusion We hypothesize that thiopental, by interfering with SPW-R activity, through enhancement of the GABAA receptor-mediated transmission, affects memory processes which involve hippocampal circuit activation. The quantity but not the frequency of ripple oscillation was affected by the drug.

  11. A review of our development of dental adhesives--effects of radical polymerization initiators and adhesive monomers on adhesion. (United States)

    Ikemura, Kunio; Endo, Takeshi


    This paper reviews the development of dental adhesives by collating information of related studies from original scientific papers, reviews, and patent literatures. Through our development, novel radical polymerization initiators, adhesive monomers, and microcapsules were synthesized, and their effects on adhesion were investigated. It was found that 5-monosubstituted barbituric acid (5-MSBA)-containing ternary initiators in conjunction with adhesive monomers contributed to effective adhesion with good polymerization reactivity. Several kinds of novel adhesive monomers bearing carboxyl group, phosphonic acid group or sulfur-containing group were synthesized, and investigated their multi-purpose bonding functions. It was suggested that the flexible methylene chain in the structure of adhesive monomers played a pivotal role in their enhanced bonding durability. It was found that the combination of acidic monomers with sulfur-containing monomer markedly improved adhesion to enamel, dentin, porcelain, alumina, zirconia, non-precious metals and precious metals. A new poly(methyl methacrylate) (PMMA)-type adhesive resin comprising microencapsulated polymerization initiators was also found to exhibit both good formulation stability and excellent adhesive property.

  12. Sedation practice for paediatric nuclear medicine procedures in Denmark related to EANM guidelines. (United States)

    Andersson, Linda; Andersen, Trine Borup; Petersen, Lars J


    The objective of this study was to examine sedation practices for paediatric nuclear medicine examinations. A questionnaire was sent to all nuclear medicine departments in Denmark about sedation practices during 2012. The response rate was 100% (18 departments). Three departments did not examine children at all. The total number of paediatric examinations among the remaining 15 sites varied from 20 to 1,583 (median 191). Sedation practice showed that approximately 50% of the sites regularly (>50% of the patients) used pharmacological sedation for renography in children aged 6-12 months and 1-3 years. A minority of centres (∼15%) regularly used sedation in children aged 0-6 months, and no sites regularly used sedation in children aged and 4-6 years. Similar findings were found for renal scintigraphy. However, one large site used no sedation in children aged 1-3 years for renography but approximately 50% of patients used it in the same age group receiving renal scintigraphy with SPET. There was a trend for reduced use of sedation with increasing total number of paediatric medicine procedures. The most frequently used agents were benzodiazepines and barbiturates. The most common route of administration was rectal, oral, and intravenous. The sedation practices varied considerably among Danish nuclear medicine departments. The sedation of children in clinical practice seemed to be more prevalent than is recommended by guidelines.

  13. Cognitive functions of epileptic patients on monotherapy with phenobarbitone and healthy controls

    Directory of Open Access Journals (Sweden)

    Mônica M. Bigarella


    Full Text Available Quantitative measurements have indicated that heredity, cerebral damage, psycho-social aspects, ictal and inter-ictal phenomena and antiepileptic drugs may interfere in the cognitive dysfunction of epileptic patients. In the present study objective methods included immediate and late recall and recognition of pictures, Stroop test and auditory selection. Twenty patients with symptomatic localized epilepsy aged 17-52 years (27±10, mean ±sd were compared to age and socially matched healthy controls. Patients were on therapeutic serum concentrations (25±12 m/mi of phenobarbitone and had active epilepsy with 1.94 generalized tonic-clonic, 0.85 simple partial and 6.28 complex partial seizures monthly (means. Patients performed worse than controls in all 6 tests (p<0.05 to p<0.001, indicating a generalized cognitive deficit related to seizures and/or barbiturate therapy. We suggest further studies should be carried out in populations with uniform monotherapeutic regimens and epileptic syndromes in order to isolate factors related to the cognitive dysfunction of epileptic patients.

  14. Injectable sodium pentobarbital: Stability at room temperature. (United States)

    Priest, Sydney M; Geisbuhler, Timothy P


    Sodium pentobarbital (Nembutal) is a barbiturate used in research as an anesthetic in many animal models. The injectable form of this drug has lately become difficult to procure and prohibitively expensive. Due to this lack of availability, researchers have begun to compound injectable sodium pentobarbital from so-called "nonpharmaceutical" pentobarbital. Some oversight agencies have objected to this practice, claiming a lack of quality control and degradation of the drug. We sought with this study to establish both: 1) a protocol for the preparation of injectable sodium pentobarbital, and 2) standard operating procedures to monitor the quality of the preparation and degradation of the drug over time. Our preparation consists of a mixture of sodium pentobarbital in alkaline aqueous solution, propylene glycol, and ethanol. Pentobarbital content in this preparation was assayed by high-pressure liquid chromatography (HPLC). We also assayed pentobarbital content over time in preparations of various ages up to 6 years old. We determined that the drug degraded at a maximum of 0.5% per year in our preparation (alkaline water/propylene glycol/ethanol) when stored in the dark at room temperature. A yellow discoloration developed after about 2 years, which we have arbitrarily determined disqualifies the preparation from use as an anesthetic. Attempts to spectroscopically assay this discoloration were not successful. Pentobarbital sodium (CID: 14075609). Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Functional sites involved in modulation of the GABAA receptor channel by the intravenous anesthetics propofol, etomidate and pentobarbital. (United States)

    Maldifassi, Maria C; Baur, Roland; Sigel, Erwin


    GABAA receptors are the major inhibitory neurotransmitter receptors in the brain and are the target for many clinically important drugs. Among the many modulatory compounds are also the intravenous anesthetics propofol and etomidate, and barbiturates. The mechanism of receptor modulation by these compounds is of mayor relevance. The site of action of these compounds has been located to subunit interfaces in the intra-membrane region of the receptor. In α1β2γ2 GABAA receptors there are five such interfaces, two β+/α- and one each of α+/β-, α+/γ- and γ+/β- subunit interfaces. We have used reporter mutations located in the second trans-membrane region in different subunits to probe the effects of changes at these subunit interfaces on modulation by propofol, etomidate and pentobarbital. We provide evidence for the fact that each of these compounds either modulates through a different set of subunit interfaces or through the same set of subunit interfaces to a different degree. As a GABAA receptor pentamer harbors two β+/α- subunit interfaces, we used concatenated receptors to dissect the contribution of individual interfaces and show that only one of these interfaces is important for receptor modulation by etomidate. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Effects of Thyrotropin-Releasing Hormone (TRH) on the Actions of Pentobarbital and Other Centrally Acting Drugs1 (United States)

    Breese, George R.; Cott, Jerry M.; Cooper, Barrett R.; Prange, Arthur J.; Lipton, Morris A.; Plotnikoff, Nicholas P.


    Thyrotropin-releasing hormone (TRH) was found to antagonize pentobarbital-induced sleeping time and hypothermia. While 3 to 100 mg/kg of TRH reduced pentobarbital sleeping time when administered prior to the barbiturate, a dose-response relationship to TRH could not be established. However, doses of 10 to 100 mg/kg of TRH enhanced the lethality of pentobarbital when these compounds were administered simultaneously. Thyrotropin or l-triiodothyronine did not imitate and hypophysectomy did not reduce the effects of TRH, indicating that the pituitary is not essential for its antagonism of pentobarbital Studies of TRH analogs provided further support of this view In addition TRH reduced the sleep and hypothermia produced by thiopental amobarbital, seco-barbital and phenobarbital, and it antagonized the hypothermia and reduced motor activity produced by chloral hydrate, reserpine, chlorpromazine and diazepam Intracisternally administered TRH also reduced pentobarbital sleeping time and hypothermia but melanocyte-stimulating hormone release-inhibiting factor and somatostatin administered by this route did not While reduction of pentobarbital sleeping time by TRH could not be attributed to an affect on monoamine systems or to deamidated TRH, this action was reduced by intracisternally administered atropine suggesting that cholinergic mechanisms may contribute to the effects of TRH. Thus the results provide evidence that TRH acts on brain independent of an effect on the pituitary. PMID:805836

  17. Network Actions of Pentobarbital in the Rat Mesopontine Tegmentum on Sensory Inflow Through the Spinothalamic Tract (United States)

    Namjoshi, Dhananjay R.; McErlane, Shelly A.; Taepavarapruk, Niwat; Soja, Peter J.


    The recent discovery of a barbiturate-sensitive “general anesthesia switch” mechanism localized in the rat brain stem mesopontine tegmental anesthesia area (MPTA) has challenged the current view of the nonspecific actions of general anesthetic agents in the CNS. In this study we provide electrophysiological evidence that the antinociception, which accompanies the behavioral state resembling general anesthesia following pentobarbital (PB) microinjections into the MPTA of awake rats, could be accompanied by the attenuation of sensory transmission through the spinothalamic tract (STT). Following bilateral microinjections of PB into the MPTA spontaneous firing rate (SFR), antidromic firing index (FI), and sciatic (Sc) as well as sural (Su) nerve-evoked responses (ER) of identified lumbar STT neurons in the isoflurane-anesthetized rat were quantified using extracellular recording techniques. Microinjections of PB into the MPTA significantly suppressed the SFR (47%), magnitudes of Sc- (26%) and Su-ER (36%), and FI (41%) of STT neurons. Microinjections of PB-free vehicle control did not alter any of the above-cited electrophysiological parameters. The results from this study suggest that antinociception, which occurs during the anesthesia-like state following PB microinjections into the MPTA, may be due, in part, to (in)direct inhibition of STT neurons via switching mechanism(s) located in the MPTA. This study provides a provenance for investigating electrophysiologically the actions on STT neurons of other current agents used clinically to maintain the state of general anesthesia. PMID:19458144

  18. Acute treatment with pentobarbital alters the kinetics of in vivo receptor binding in the mouse brain

    Energy Technology Data Exchange (ETDEWEB)

    Sakiyama, Yojiro [Division of Clinical Research, National Institute of Radiological Sciences, Inage-ku, Chibashi 263-8555 (Japan)]. E-mail:; Saito, Masao [Department of Medical Science, Institute of Medical Electronics, University of Tokyo, Bunkyo-ku, Tokyo 113-0033 (Japan); Inoue, Osamu [Department of Medical Physics, School of Allied Health Science, Faculty of Medicine, Osaka University, Suita, Osaka 565-0871 (Japan)


    The effect of pentobarbital, a sedative-hypnotic barbiturate, on the in vivo binding of benzodiazepine receptors in the mouse brain was investigated. Dose-related changes in the apparent binding of [{sup 3}H]Ro15-1788 ([{sup 3}H]flumazenil) in the cerebral cortex, cerebellum and pons-medulla were observed by pretreatment with pentobarbital. For quantification of the kinetic properties of the in vivo binding of [{sup 3}H]Ro15-1788, time courses of radioactivity following its injection were examined, and kinetic analysis was performed using the compartment model. The time courses of radioactivity following injection of [{sup 3}H]Ro15-1788 with 3 mg/kg Ro15-1788 were used as input function. In all regions studied, rate constants between input compartment and specific binding compartment were significantly decreased by pentobarbital. However, no significant alterations in the binding potential (BP=K {sub 3}/K {sub 4}) of benzodiazepine receptors by pentobarbital were observed in any of the regions. A saturation experiment indicated that the decrease in the input rate constant (K {sub 3}), which includes both the association rate constant (k {sub on}) and the number of binding sites available (B {sub max}), was mainly due to decrease in k {sub on}. These results suggest that apparent increases in binding at 20 min after tracer injection were due to the decrease in the association and dissociation rates of binding in vivo.

  19. Tartrazine induced neurobiochemical alterations in rat brain sub-regions. (United States)

    Bhatt, Diksha; Vyas, Krati; Singh, Shakuntala; John, P J; Soni, Inderpal


    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 (7.5 mg/kg b.w.) was administered to 21 day old weanling rats through oral gavage once daily for 40 consecutive days. On 41st day, the animals were sacrificed and brain sub regions namely, frontal cortex, corpus striatum, hippocampus and cerebellum were used to determine activities of anti-oxidant enzymes viz. Superoxide Dismutase (SOD), Catalase (CAT), Glutathione-Stransferase (GST), Glutathione Reductase (GR) and Glutathione Peroxidase (GPx) and levels of lipid peroxides using Thio-barbituric Acid Reactive Substance (TBARS) assay. Our investigation showed a significant decrease in SOD and CAT activity, whereas there occurred a decline in GST and GR activity with an increase in GPx activity to counteract the oxidative damage caused by significantly increased levels of lipid peroxides. The possible mechanism of this oxidative damage might be attributed to the production of sulphanilc acid as a metabolite in azofission of tartrazine. It may be concluded that the ADI levels of food azo dyes adversely affect and alter biochemical markers of brain tissue and cause oxidative damage. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Avaliação dos efeitos depressores centrais do extrato etanólico das folhas de Synadenium umbellatum Pax. e de suas frações em camundongos albinos Evaluation of the central depressor effects of the ethanolic extract of the leaves of Synadenium umbellatum Pax. and its fractions in Swiss mice

    Directory of Open Access Journals (Sweden)

    Rodrigo Borges de Oliveira


    Full Text Available O Synadenium umbellatum Pax. (Euphorbiacea é uma planta nativa da África tropical conhecida como "cola-nota", "avelós", "cancerola", "milagrosa", dentre outros. A planta é utilizada pela população brasileira como detentora de propriedades antiinflamatória, analgésica, dentre outras. Foram avaliados os efeitos depressores sobre o sistema nervoso central (SNC do extrato etanólico das folhas de Synadenium umbellatum (EES e de suas frações - hexânica (FH, clorofórmica (FC e metanol/água (FM. Vários testes foram utilizados em camundongos machos albinos (Mus musculus, dentre eles, o sono induzido por barbitúrico, campo aberto e o teste do rota-rod. O EES foi testado nas doses de 25, 50 e 100 mg/kg, enquanto que a FH foi testada na dose de 10 mg/kg, a FC na dose de 20 mg/kg e a FM na dose de 25 mg/kg. O EES e as frações FH e FC, mas não a FM, apresentaram um possível efeito depressor sobre o SNC, visto que foram capazes de aumentar o tempo parado e diminuir o número de bolos fecais no campo aberto, além de potencializarem o sono induzido por barbitúrico. No teste do rota-rod, observou-se que o EES e as frações não foram capazes de causar incoordenação motora ou relaxamento muscular. Assim, conclui-se que o extrato etanólico e as frações FH e FC do Syandenium umbellatum Pax. possuem possível efeito depressor sobre o SNC.Synadenium umbellatum Pax. (Euphorbiacea is a native plant from tropical Africa known as "cola-nota", "avelós", "cancerola", "milagrosa", among others. The plant is used by Brazilian folks for having anti-inflammatory and analgesic properties, among others. It was evaluated the depressor effects over the central nervous system (CNS of the ethanolic extract of the leaves of Synadenium umbellatum (EES and its fractions - hexane (HF, chloroformic (CF and methanol/water fractions(MF. Several tests were used in Swiss mice (Mus musculus, among them, barbiturate-induced sleep, open field and rota-rod test. The

  1. Efeitos do pentobarbital sódico sobre a atividade elétrica cerebral do rato com lesões da formação reticular mesencefálica Action of sodium pentobarbital on the cortical electrical activity of the rat after lesion of the midbrain reticular formation

    Directory of Open Access Journals (Sweden)

    Walter C. Pereira


    acut and 18 for chronic experiments. The midbrain reticular formation was electrolytically destroyed on both sides in 24 animals, and in 11 on one side. The interruption of the reticular activating system was checked by strong nociceptive and electrical stimulation below the lesioned area. In acute preparations pentobarbital was given by intravenous injection in increasing doses, and in chronic experiments by intraperitoneal injections. The barbiturate always augmented synchronization of the electrocorticogram but induced an early depression of the electrical activity in rats with bilateral extensive lesions. After barbiturate administration the electro-corticogram of both hemispheres tended to became more isochronized. Pentobarbital seems to depress the activating systems in small doses, thus liberating the synchronizing systems, whereas larger doses block also the latter. Only very large doses depress the cortical activity.

  2. Desenvolvimento e validação de um método cromatográfico em fase gasosa para análise da 3,4-metilenodioximetanfetamina (ecstasy e outros derivados anfetamínicos em comprimidos Development and validation of a gas chromatography method for determination of ecstasy and amphetamines derivatives in tablets

    Directory of Open Access Journals (Sweden)

    Marcelo Carvalho Lasmar


    laboratories of toxicology of the development countries as Brazil. It was chosen for development and validation a gas chromatography method with flame ionization detection. The analytic validation results for MDMA, MDA and MDEA were linearity range of 1.0 to 500.0 µg/mL, intra and interassay coefficient of variation lower than 9.5% and quantification limit of 1.0 µg/mL. The detection limits were 0.7 µg/mL, 0.8 µg/mL and 0.6 µg/mL respectively to MDMA, MDA and MDEA. The method showed a good seletivity as the epinephrine, cocaine, amphetamine, methamphetamine, acethyl salicilic acid, diethyl barbituric acid, p-aminobenzoyl diethyl barbituric, paracetamol and caffeine presences did not interfere with the measurement of the three analytes.

  3. The use of propofol for procedural sedation in emergency departments. (United States)

    Wakai, Abel; Blackburn, Carol; McCabe, Aileen; Reece, Emilia; O'Connor, Ger; Glasheen, John; Staunton, Paul; Cronin, John; Sampson, Christopher; McCoy, Siobhan C; O'Sullivan, Ronan; Cummins, Fergal


    There is increasing evidence that propofol is efficacious and safe for procedural sedation (PS) in the emergency department (ED) setting. However, propofol has a narrow therapeutic window and lacks of a reversal agent. The aim of this review was to cohere the evidence base regarding the efficacy and safety profile of propofol when used in the ED setting for PS. To identify and evaluate all randomized controlled trials (RCTs) comparing propofol with alternative drugs (benzodiazepines, barbiturates, etomidate and ketamine) used in the ED setting for PS. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9), MEDLINE (1950 to September week 2 2013) and EMBASE (1980 to week 2 2013). We searched the Current Controlled Trials metaRegister of Clinical Trials (compiled by Current Science) (September 2013). We checked the reference lists of trials and contacted trial authors. We imposed no language restriction. We re-ran the search in February 2015. We will deal with the one study awaiting classification when we update the review. RCTs comparing propofol to alternative drugs (benzodiazepines, barbiturates, etomidate and ketamine) used in the ED setting for PS in participants of all ages. Two authors independently performed data extraction. Two authors performed trial quality assessment. We used mean difference (MD), odds ratio (OR) and 95% confidence intervals (CI) to measure effect sizes. Two authors independently assessed and rated the methodological quality of each trial using The Cochrane Collaboration tool for assessing risk of bias. Ten studies (813 participants) met the inclusion criteria. Two studies only included participants 18 years and younger; six studies only included participants 18 years and older; one study included participants between 16 and 65 years of age and one study included only adults but did not specify the age range. Eight of the included studies had a high risk of bias. The included studies

  4. Alcohol or Drug Use and Trauma Recidivism. (United States)

    Cordovilla-Guardia, Sergio; Vilar-López, Raquel; Lardelli-Claret, Pablo; Guerrero-López, Francisco; Fernández-Mondéjar, Enrique

    Alcohol, illicit drugs, and psychotropic medications are well-known causes of traumatic events. However, the association of each type of substance with trauma recidivism remains unclear. The purpose of this study was to quantify the strength of associations between the type of substance detected in patients admitted for traumatic injury and trauma recidivism, defined as a documented history of past trauma. The presence of alcohol and drugs (cannabis, cocaine, amphetamines, methamphetamines, benzodiazepines, opiates, methadone, barbiturates, and tricyclic antidepressants) was analyzed in 1,156 patients between 16 and 70 years old, hospitalized in a trauma hospital between November 2011 and March 2015. Their past trauma history was retrieved from the health information system, which included patient health histories since 1999. Multinomial logistic regression analysis was used to estimate the strength of the association between types of substances detected in current trauma patients and trauma recidivism (documented history of past trauma). At least one substance was detected in 521 patients (45.1%): only alcohol in 159 (13.7%), only cannabis in 62 (5.4%), only psychotropic medications/opioids in 145 (12.5%), only cocaine/amphetamines in 14 (1.2%), and a combination of these groups in 141 (12.2%). The consumption of alcohol, illicit drugs, and/or psychotropic medications was associated with increased recidivism in all substance groups; the adjusted odds ratio for multiple recidivism was 3.17 (95% CI [2.29, 4.39]). Patients who screened positive for alcohol, illicit drugs, and/or psychotropic medications had a higher frequency of past trauma history compared with patients with negative tests, independently of age, gender, or the presence of previous psychiatric disorders.

  5. Biological effects of Ocimum gratissimum L. are due to synergic action among multiple compounds present in essential oil. (United States)

    Galindo, Luciane Almeida; Pultrini, Aline de Moraes; Costa, Mirtes


    Species of genus Ocimum (Lamiaceae) are economically important due to their essential oils and utilization as medicine for many disorders, including the central nervous system. A previous study showed seasonal variations in chemical profile and in central nervous system activities of essential oil from Ocimum gratissimum L. The preparation obtained in spring was able to protect the animals against tonic episodes induced by electroshock while those obtained in other seasons were effective in increasing barbiturate-induced sleeping time. The chemical analysis of essential oils showed eugenol and 1,8-cineole as principal compounds and trans-caryophyllene as a sesquiterpene in higher proportion. In the present study these three compounds were evaluated, separately or mixed in the same proportion detected in spring, in the open-field and rota-rod tests, against convulsions induced by pentylenetetrazole (PTZ; 60 mg/kg, subcutaneously, s.c.) or maximal electroshock (MES; 50 mA, 0.11 s) and in sodium pentobarbital (45 mg/kg, intraperitoneally, i.p.)-induced sleeping time. The compounds, isolated or in association, did not show efficaciousness in altering convulsive episodes, and only when in association were able to increase sleeping time duration. The absence of similar essential oil activity in the isolated compounds contributes to the idea that the major compounds are not always responsible for a biological effect observed in medicinal plant preparations. This view reinforces the concept of a multitargeted approach as a therapeutic strategy, contributing to an integrated understanding of the phenomena related to experimental activity of a complex herbal mixture.

  6. The benzodiazepine diazepam potentiates responses of α1β2γ2 γ-aminobutyric acid type A receptors activated by either γ-aminobutyric acid or allosteric agonists (United States)

    Li, Ping; Eaton, Megan M.; Steinbach, Joe Henry; Akk, Gustav


    Background The γ-aminobutyric acid type A receptor is target for several anesthetics, anticonvulsants, anxiolytics and sedatives. Neurosteroids, barbiturates and etomidate both potentiate responses to γ-aminobutyric acid (GABA) and allosterically activate the receptor. We examined the ability of a benzodiazepine, diazepam, to potentiate responses to allosteric agonists. Methods The γ-aminobutyric acid type A receptors were expressed in human embryonic kidney 293 cells, and studied using whole-cell and single-channel patch clamp. The receptors were activated by the orthosteric agonist GABA, and allosteric agonists pentobarbital, etomidate and alfaxalone. Results Diazepam is equally potent at enhancing responses to orthosteric and allosteric agonists. Diazepam EC50s were 25±4, 26±6, 33±6, and 26±3 nM for receptors activated by GABA, pentobarbital, etomidate, and alfaxalone, respectively (mean±S.D., 5–6 cells at each condition). Mutations to the benzodiazepine-binding site (α1(H101C), γ2(R144C), γ2(R197C)) reduced or removed potentiation for all agonists, and an inverse agonist at the benzodiazepine site reduced responses to all agonists. Single-channel data elicited by GABA demonstrate that in the presence of 1 μM diazepam the prevalence of the longest open-time component is increased from 13±7 (mean±S.D., n=5 patches) to 27±8 % (n=3 patches) and the rate of channel closing is decreased from 129±28 s−1 to 47±6 s−1 (mean±S.D.) Conclusions We conclude that benzodiazepines do not act by enhancing affinity of the orthosteric site for GABA but rather by increasing channel gating efficacy. The results also demonstrate the presence of significant interactions between allosteric activators and potentiators, raising a possibility of effects on dosage requirements or changes in side effects. PMID:23407108

  7. Early drug discovery and the rise of pharmaceutical chemistry. (United States)

    Jones, Alan Wayne


    Studies in the field of forensic pharmacology and toxicology would not be complete without some knowledge of the history of drug discovery, the various personalities involved, and the events leading to the development and introduction of new therapeutic agents. The first medicinal drugs came from natural sources and existed in the form of herbs, plants, roots, vines and fungi. Until the mid-nineteenth century nature's pharmaceuticals were all that were available to relieve man's pain and suffering. The first synthetic drug, chloral hydrate, was discovered in 1869 and introduced as a sedative-hypnotic; it is still available today in some countries. The first pharmaceutical companies were spin-offs from the textiles and synthetic dye industry and owe much to the rich source of organic chemicals derived from the distillation of coal (coal-tar). The first analgesics and antipyretics, exemplified by phenacetin and acetanilide, were simple chemical derivatives of aniline and p-nitrophenol, both of which were byproducts from coal-tar. An extract from the bark of the white willow tree had been used for centuries to treat various fevers and inflammation. The active principle in white willow, salicin or salicylic acid, had a bitter taste and irritated the gastric mucosa, but a simple chemical modification was much more palatable. This was acetylsalicylic acid, better known as Aspirin®, the first blockbuster drug. At the start of the twentieth century, the first of the barbiturate family of drugs entered the pharmacopoeia and the rest, as they say, is history. Copyright © 2011 John Wiley & Sons, Ltd.

  8. Steroid modulation of the chloride ionophore in rat brain: structure-activity requirements, regional dependence and mechanism of action

    Energy Technology Data Exchange (ETDEWEB)

    Gee, K.W.; Bolger, M.B.; Brinton, R.E.; Coirini, H.; McEwen, B.S.


    Further in vitro studies of steroids active at the gamma-aminobutyric acidA (GABAA) receptor regulated Cl- channel labeled by (35S)-t-butylbicyclophosphorothionate ((35S)TBPS) reveal additional structural requirements necessary for activity. Evaluation of selected steroids for activity against TBPS-induced convulsions show similar requirements for activity. Interestingly, steroids (e.g., 5 alpha-pregnan-3 alpha, 20 alpha-diol) were identified that have high potency but limited efficacy as modulators of (35S)TBPS binding. These characteristics are reminiscent of the clinically useful benzodiazepines (BZs) such as clonazepam. However, interactions between the prototypical anesthetic-barbiturate, sodium pentobarbital, and steroids active at the Cl- channel suggest that they do not share a common site of action as allosteric modulators of (35S)TBPS and BZ receptor binding. The most potent steroid evaluated, 5 alpha-pregnan-3 alpha-ol-20-one, modulates (35S)TBPS binding at low concentrations (IC50 approximately 17 nM) in a regionally dependent manner. All (35S)TBPS binding sites appear to be functionally coupled to a steroid modulatory site. Because several of the active steroids are metabolites of progesterone, their ability to inhibit the binding of (3H)promegestrone to the cytosolic progestin receptor in rat uterus was evaluated. Those steroids showing potent activity at the GABAA receptor-Cl- ionophore were inactive at the intracellular progestin receptor. Such specificity coupled with their high potency provide additional support for the hypothesis that some of these steroids may be involved in the homeostatic regulation of brain excitability via the GABAA-BZ receptor complex.

  9. Evolução sócio-profissional de 140 pacientes epilépticos submetidos a tratamento medicamentoso The socio-professional evolution of 140 epileptic patients submitted to antiepileptic drug therapy

    Directory of Open Access Journals (Sweden)

    Luís Marques-Assis


    Full Text Available É estudada a evolução sócio-profissional de 140 doentes epilépticos, submetidos apenas a tratamento medicamentoso. Foram empregadas drogas de fácil aquisição em nosso meio (barbitúricos, hidantoinatos, primidona e trimetadiona, utilizadas isolada ou combinadamente. No estudo foram consideradas basicamente as atividades escolares, domésticas e profissionais. A evolução sócio-profissional foi estudada em relação às manifestações clínicas, ao tempo de doença, à freqüência das crises e ao padrão eletrencefalográfico. Os resultados, expressos em índices percentuais, permitiram ao autor concluir que na maioria dos pacientes epilépticos, convenientemente tratados do ponto de vista clínico, os problemas sociais e profissionais podem ser corrigidos ou evitados, independentemente de outras medidas especializadas que possam ser postas em prática.The socio-professional evolution of 140 epileptic patients submitted to antiepileptic drug therapy is studied. Only barbiturates, hydantoin, primidone and trimethadione were administered to the patients, isolated or in association. The school, house keeper and professional activities were considered in the investigation. The socio-professional follow-up was investigated regarding to clinic manifestations, time of disease, frequency of seizures and electroencephalographic pattern. The results, analysed in percentage, led the author to the conclusion that in most epileptic patients, adequately controlled with drugs, the social and the professional problems can be avoided.

  10. End-of-life practices in the Netherlands under the Euthanasia Act. (United States)

    van der Heide, Agnes; Onwuteaka-Philipsen, Bregje D; Rurup, Mette L; Buiting, Hilde M; van Delden, Johannes J M; Hanssen-de Wolf, Johanna E; Janssen, Anke G J M; Pasman, H Roeline W; Rietjens, Judith A C; Prins, Cornelis J M; Deerenberg, Ingeborg M; Gevers, Joseph K M; van der Maas, Paul J; van der Wal, Gerrit


    In 2002, an act regulating the ending of life by a physician at the request of a patient with unbearable suffering came into effect in the Netherlands. In 2005, we performed a follow-up study of euthanasia, physician-assisted suicide, and other end-of-life practices. We mailed questionnaires to physicians attending 6860 deaths that were identified from death certificates. The response rate was 77.8%. In 2005, of all deaths in the Netherlands, 1.7% were the result of euthanasia and 0.1% were the result of physician-assisted suicide. These percentages were significantly lower than those in 2001, when 2.6% of all deaths resulted from euthanasia and 0.2% from assisted suicide. Of all deaths, 0.4% were the result of the ending of life without an explicit request by the patient. Continuous deep sedation was used in conjunction with possible hastening of death in 7.1% of all deaths in 2005, significantly increased from 5.6% in 2001. In 73.9% of all cases of euthanasia or assisted suicide in 2005, life was ended with the use of neuromuscular relaxants or barbiturates; opioids were used in 16.2% of cases. In 2005, 80.2% of all cases of euthanasia or assisted suicide were reported. Physicians were most likely to report their end-of-life practices if they considered them to be an act of euthanasia or assisted suicide, which was rarely true when opioids were used. The Dutch Euthanasia Act was followed by a modest decrease in the rates of euthanasia and physician-assisted suicide. The decrease may have resulted from the increased application of other end-of-life care interventions, such as palliative sedation. Copyright 2007 Massachusetts Medical Society.

  11. Anaesthetic and other treatments of shell shock: World War I and beyond. (United States)

    McKenzie, A G


    Post-traumatic stress disorder (PTSD) is an important health risk factor for military personnel deployed in modern warfare. In World War I this condition (then known as shell shock or 'neurasthenia') was such a problem that 'forward psychiatry' was begun by French doctors in 1915. Some British doctors tried general anaesthesia as a treatment (ether and chloroform), while others preferred application of electricity. Four British 'forward psychiatric units' were set up in 1917. Hospitals for shell shocked soldiers were also established in Britain, including (for officers) Craiglockhart War Hospital in Edinburgh; patients diagnosed to have more serious psychiatric conditions were transferred to the Royal Edinburgh Asylum. Towards the end of 1918 anaesthetic and electrical treatments of shell shock were gradually displaced by modified Freudian methods psychodynamic intervention. The efficacy of 'forward psychiatry' was controversial. In 1922 the War Office produced a report on shell shock with recommendations for prevention of war neurosis. However, when World War II broke out in 1939, this seemed to have been ignored. The term 'combat fatigue' was introduced as breakdown rates became alarming, and then the value of pre-selection was recognised. At the Maudsley Hospital in London in 1940 barbiturate abreaction was advocated for quick relief from severe anxiety and hysteria, using i.v. anaesthetics: Somnifaine, paraldehyde, Sodium Amytal. 'Pentothal narcosis' and 'narco-analysis' were adopted by British and American military psychiatrists. However, by 1945 medical thinking gradually settled on the same approaches that had seemed to be effective in 1918. The term PTSD was introduced in 1980. In the UK the National Institute for Health and Clinical Excellence (NICE) guidelines for management (2005) recommend trauma-focussed Cognitive Behavioural Therapy and consideration of antidepressants.

  12. Doping control in Japan. An automated extraction procedure for the doping test. (United States)

    Nakajima, T.; Matsumoto, T.


    Horse racing in Japan consists of two systems, the National (10 racecourses) and the Regional public racing (32 racecourses) having about 2,500 racing meetings in total per year. Urine or saliva samples for dope testing are collected by the officials from thw winner, second and third, and transported to the laboratory in a frozen state. In 1975, 76, 117 samples were analyzed by this laboratory. The laboratory provides the following four methods of analysis, which are variously combined by request. (1) Method for detection of drugs extracted by chloroform from alkalinized sample. (2) Methods for detection of camphor and its derivatives. (3) Method for detection of barbiturates. (4) Method for detection of ethanol. These methods consist of screening, mainly by thin layer chromatography and confirmatory tests using ultra violet spectrophotometry, gas chromatography and mass spectrometry combined with gas chromatography. In the screening test of doping drugs, alkalinized samples are extracted with chloroform. In order to automate the extraction procedure, the authors contrived a new automatic extractor. They also devised a means of pH adjustment of horse urine by using buffer solution and an efficient mechanism of evaporation of organic solvent. Analytical data obtained by the automatic extractor are presented in this paper. In 1972, we started research work to automate the extraction procedure in method (1) above, and the Automatic Extractor has been in use in routine work since last July. One hundred and twnety samples per hour are extracted automatically by three automatic extractors. The analytical data using this apparatus is presented below. PMID:1000163

  13. Excitatory amino acid receptor-mediated transmission of somatosensory evoked potentials in the rat thalamus. (United States)

    Klockgether, T


    1. To examine the role of excitatory amino acid receptors in the rat ventrobasal thalamic nucleus (v.b.t.n.) for the transmission of cortical somatosensory evoked potentials (s.e.p.s), potentials were recorded from the somatosensory cortex of barbiturate-anaesthetized and of unanaesthetized awake rats. The effects of microapplications of the selective N-methyl-D-aspartate (NMDA) antagonist (-)-2-amino-7-phosphono-heptanoate ((-)AP7) and the broad-spectrum excitatory amino acid antagonist 1-(p-chlorobenzoyl)-piperazine-2,3-dicarboxylate (pCB-PzDA) into the thalamus on the amplitudes and latencies of cortical potentials were measured. 2. To define the receptor specificity of local microinjections of (-)AP7 and pCB-PzDA electroencephalogram (e.e.g.) recordings were made from the immediate vicinity of the injection cannula within the thalamus. (-)AP7 selectively antagonized epileptic discharges induced by NMDA, but not those by kainate, whereas pCB-PzDA antagonized epileptic discharges induced by both. 3. In both anaesthetized and unanaesthetized rats, microapplications of pCB-PzDA into the thalamus suppressed transmission of cortical potentials as indicated by a decrease of their amplitudes and an increase of their peak latencies. Further experiments in anaesthetized rats showed that pCB-PzDA exerted its effects in a dose-dependent and site-specific way. 4. In both anaesthetized and unanaesthetized rats, microapplications of (-)AP7 into the ventrobasal thalamus did not affect cortical potentials. 5. These results are consistent with the assumption that an excitatory amino acid serves as transmitter at thalamic synapses mediating transmission of cortical potentials, and that this transmitter interacts preferentially with non-NMDA receptors.

  14. A Multifaceted GABAA Receptor Modulator: Functional Properties and Mechanism of Action of the Sedative-Hypnotic and Recreational Drug Methaqualone (Quaalude) (United States)

    Hammer, Harriet; Bader, Benjamin M.; Ehnert, Corina; Bundgaard, Christoffer; Bunch, Lennart; Hoestgaard-Jensen, Kirsten; Schroeder, Olaf H.-U.; Bastlund, Jesper F.; Gramowski-Voß, Alexandra


    In the present study, we have elucidated the functional characteristics and mechanism of action of methaqualone (2-methyl-3-o-tolyl-4(3H)-quinazolinone, Quaalude), an infamous sedative-hypnotic and recreational drug from the 1960s–1970s. Methaqualone was demonstrated to be a positive allosteric modulator at human α1,2,3,5β2,3γ2S GABAA receptors (GABAARs) expressed in Xenopus oocytes, whereas it displayed highly diverse functionalities at the α4,6β1,2,3δ GABAAR subtypes, ranging from inactivity (α4β1δ), through negative (α6β1δ) or positive allosteric modulation (α4β2δ, α6β2,3δ), to superagonism (α4β3δ). Methaqualone did not interact with the benzodiazepine, barbiturate, or neurosteroid binding sites in the GABAAR. Instead, the compound is proposed to act through the transmembrane β(+)/α(–) subunit interface of the receptor, possibly targeting a site overlapping with that of the general anesthetic etomidate. The negligible activities displayed by methaqualone at numerous neurotransmitter receptors and transporters in an elaborate screening for additional putative central nervous system (CNS) targets suggest that it is a selective GABAAR modulator. The mode of action of methaqualone was further investigated in multichannel recordings from primary frontal cortex networks, where the overall activity changes induced by the compound at 1–100 μM concentrations were quite similar to those mediated by other CNS depressants. Finally, the free methaqualone concentrations in the mouse brain arising from doses producing significant in vivo effects in assays for locomotion and anticonvulsant activity correlated fairly well with its potencies as a modulator at the recombinant GABAARs. Hence, we propose that the multifaceted functional properties exhibited by methaqualone at GABAARs give rise to its effects as a therapeutic and recreational drug. PMID:26056160

  15. Suppression of motor cortical excitability in anesthetized rats by low frequency repetitive transcranial magnetic stimulation.

    Directory of Open Access Journals (Sweden)

    Paul A Muller

    Full Text Available Repetitive transcranial magnetic stimulation (rTMS is a widely-used method for modulating cortical excitability in humans, by mechanisms thought to involve use-dependent synaptic plasticity. For example, when low frequency rTMS (LF rTMS is applied over the motor cortex, in humans, it predictably leads to a suppression of the motor evoked potential (MEP, presumably reflecting long-term depression (LTD -like mechanisms. Yet how closely such rTMS effects actually match LTD is unknown. We therefore sought to (1 reproduce cortico-spinal depression by LF rTMS in rats, (2 establish a reliable animal model for rTMS effects that may enable mechanistic studies, and (3 test whether LTD-like properties are evident in the rat LF rTMS setup. Lateralized MEPs were obtained from anesthetized Long-Evans rats. To test frequency-dependence of LF rTMS, rats underwent rTMS at one of three frequencies, 0.25, 0.5, or 1 Hz. We next tested the dependence of rTMS effects on N-methyl-D-aspartate glutamate receptor (NMDAR, by application of two NMDAR antagonists. We find that 1 Hz rTMS preferentially depresses unilateral MEP in rats, and that this LTD-like effect is blocked by NMDAR antagonists. These are the first electrophysiological data showing depression of cortical excitability following LF rTMS in rats, and the first to demonstrate dependence of this form of cortical plasticity on the NMDAR. We also note that our report is the first to show that the capacity for LTD-type cortical suppression by rTMS is present under barbiturate anesthesia, suggesting that future neuromodulatory rTMS applications under anesthesia may be considered.


    López-Crespo, Rubén A; López-Mayagoitia, Alfonso; Ramírez-Romero, Rafael; Martínez-Burnes, Julio; Prado-Rebolledo, Omar F; García-Márquez, Luis J


    Didelphostrongylus hayesi is an important and prevalent pulmonary nematode in the opossum ( Didelphis virginiana ). An in-depth description of the pulmonary lesions caused by this nematode is lacking. The objective of this investigation was to make a detailed account of the gross, subgross, and microscopic changes that occur in the lungs of opossums naturally infected with D. hayesi. Forty-four opossums trapped in the state of Colima, Mexico, were euthanized by an overdose of barbiturates. Following a postmortem examination, the right lung was cut from the main bronchi and placed in a Petri dish containing a saline solution for the detection and identification of live parasites. The left lung was fixed and cut serially for subgross microscopic examination and sections of lung were cut and stained for histopathologic examination. The most remarkable gross change in parasitized lungs was a poorly collapsible pulmonary parenchyma and mild emphysema. The right lung tested positive for lungworms on gross examination in 20/44, and 11/44 (25%) of the left lungs showed tan nodules on the pleural surface. Microscopically, the bronchi of 20/44 animals harbored adult and larval stages of D. hayesi (left lung), the same 20 opossums from which nematodes were grossly evident at necropsy (right lung). Adults and larvae were present in bronchi, bronchioles, and alveoli mixed with desquamated cells and many eosinophils, and to a lesser extent neutrophils, alveolar macrophages, and giant cells. Bronchi and bronchioles exhibited goblet cell hyperplasia and metaplasia respectively, and infiltration of lymphoplasmacytic cells in the interstitium and lamina propria. The tan nodules consisted of focal alveolar endogenous lipidosis, which likely resulted from parasitic airway obstruction. The lungs of 3/20 parasitized opossums also showed alveolar bronchiolization (Lambertosis). The absence of Eucoleus aerophilus or bacterial pneumonia incriminates D. hayesi as the putative cause of

  17. The effect of Cerasus avium stalk extract on albumin glycation reaction

    Directory of Open Access Journals (Sweden)

    Mohadeseh Abdoli


    Full Text Available Background: Non-enzymatic glycosylation of proteins is the major cause of diabetic complications. The inhibition of glycation process can reduce complications of diabetes. In the Iranian traditional medicine, the decoction (boiled extraction of Cerasus avium stalk is used as a hypoglycemic agent. The aim of this study was to investigate the in vitro inhibitory effects of decoction and ethanolic and aqueous extracts of Cerasus avium stalk on albumin glycation reaction. Methods: In this experimental study, first, the ethanolic, aqueous and decoction extracts of Cerasus avium stalk were prepared. Then, different concentrations of these extracts were prepared and added to albumin and glucose solutions. Finally, compared to control group that was not treated with any extracts, the albumin glycation rate in the groups treated with various concentrations of extracts was evaluated using TBA (thio-barbituric acid method. Results: The results showed that compared to control group, decoction of Cerasus avium stalk in the concentrations of 20, 10 and 2 mg/dl could reduce albumin glycation to 85.10±1.55, 72.35±1.75 and 51.25±1.22 %, respectively (P>0.001. Moreover, in the concentration of 20 mg/dl, the inhibitory effect of decoction of Cerasus avium stalk on the albumin glycation reaction was higher than those of aqueous (P=0.021 and ethanolic (P=0.009 extracts. Conclusion: The findings showed that the extracs of Cerasus avium stalk, in particular in the decoction form, could significantly reduce the rate of albumin glycation; therefore, it can be used for decreasing diabetes mellitus complications.

  18. Genetic effects of decay of tritium incorporated into cells of yeast Saccharomyces cerevisiae. 5. Lethal and mutagenic effects and the nature of mutations induced by /sup 3/H decay in the 6-th position of thymine

    Energy Technology Data Exchange (ETDEWEB)

    Ivanov, E.L.; Korolev, V.G. (AN SSSR, Leningrad. Inst. Yadernoj Fiziki)


    Lethal and mutagenous effects as well as nature of mutations induced with /sup 3/H decay in the sixth position of thymine (6-/sup 3/H-T) have been studied. Inactivation probability of haploid yeasts constituted ..cap alpha..=(6.1+-1.0)x10/sup -3/ decay/sup -1/ or ..cap alpha..=(7.6+-1.3)x10/sup -5/ rad/sup -1/, and probability of mutation appearance in genes ade 1, ade -K is (2.8+-1.7)x10/sup -8/ decay/sup -1/ or K=(3.5+-2.1)x10/sup -10/ rad/sup -1/. Lethal and mutageneous effects of 6-/sup 3/H-T don't differ considerably from those for /sup 3/H decay in the fifth position of thymine (5-/sup 3/H-T). From the point of view of frequency of transversions and mutations of read-out frame shift type induced in ade 2 gene, 6-/sup 3/H-T doesn't differ from 5-/sup 3/H-T. However, in comparison with the latter 6-/sup 3/H-T causes appearance of a larger amount of AT ..-->.. GTs transitions. A scheme, according to which 5 methyl barbituric acid (5MBK) is a finite product of /sup 3/H decay in the sixth position of thymine, is suggested. The results obtained point to that fact that 5MBK represents weak mutageneous damage of thymine causing the exchange of AT pair.

  19. Dietary effects of oregano (Origanum vulgaris L. plant or sweet chestnut (Castanea sativa Mill. wood extracts on microbiological, chemical-physical characteristics and lipid oxidation of cooked ham during storage

    Directory of Open Access Journals (Sweden)

    David Ranucci


    Full Text Available The aim of this study was to evaluate the dietary effect of feeding pigs with diets enriched with sweet chestnut wood (Castanea sativa Mill. or oregano (Origanum vulgaris L. extract on the microbiological and chemical characteristics of cooked pork ham. Three groups of 10 pigs were fed with a control diet (CTRL, with the CTRL diet enriched with 0.2% of oregano extract (OR and with the CTRL diet enriched with 0.2% of sweet chestnut wood extract (SCW, respectively. Six cooked hams per group were produced, sliced and packaged under a modified atmosphere (N2:CO2=80:20 and stored at refrigeration temperature (4±1°C. Three packages per cooked ham were sampled for analyses at three different storage times (0, 10 and 20 days. At day 0 time, antioxidant capacity of the products (ORACFL assay and chemical composition were performed. At each sampling time, from all the samples the following analyses were performed: Total Microbial Count (TMC, Lactic Acid Bacteria count (LAB, Enterobacteriaceae count, Listeria monocytogenes, pH value, colour coordinates (L*, a*, b*, total basic volatile nitrogen (TBVN and thio-barbituric reactive substances (TBARs determinations. No differences in TMC, LAB and Enterobacteriaceae count, pH, TBVN, chemical composition and L* values were registered between the three groups at all the sampling times considered. No Listeria monocytogenes was detected in the samples tested. Significant differences were registered for ORACFL at 0 days, a* and b* values and TBARs value at 10 and 20 days of storage, with higher values for ORACFL, a* and b* values and lower values for TBARs in SCW and OR than CTRL. No antimicrobial effect could be recorded for OR and SCW but a higher oxidative stability, also highlighted by the colour maintenance, was observed in both OR and SCW.

  20. Aspiration Deaths Among Adults in Istanbul

    Directory of Open Access Journals (Sweden)

    Haşim Asil


    Full Text Available Massive aspiration of food is rare, but most common in people under the influence of alcohol or a drug and comatose patients who have impaired functioning of the central nervous system. The finding of small amounts of food material in the airway at autopsy does not indicate the true vital aspiration because of agonal or even early post-mortem overspills. Occlusion of the small airways, mainly the membranous and respiratory bronchioles, partial or total filling of bronchiolar lumen and the alveolar spaces with food or gastric content were typical morphologic findings. In our 10 year retrospective study we presented the data of 21 male and 4 female cases with a final diagnosis of fatal aspiration in age from 23 to 78 years (45.43±14.61 from the records of Morgue Specialization Department of the Council of Forensic Medicine. 13 cases found death at the scene without an eyewitness. All deaths were accidental in manner except one homicide. Toxicological analysis revealed blood alcohol concentration levels between 161 and 339 mg/dL in 7 cases. Morphine metabolites, benzodiazepine and barbituric acid derivatives, toluene and acetone were detected in 5 subjects. Aspirated materials were food in 14 cases, chewing gum in 3 cases, gastric content in 7 cases and a fabric gag in one case. The history, other evidence of external vomit on the clothing or immediate surroundings and toxicological analysis are by no means as significant as autopsy findings especially in cases of aspiration. Key words : adult; aspiration; death; autopsy

  1. Antioxidant and anti hyperglycemic role of wine grape powder in rats fed with a high fructose diet

    Directory of Open Access Journals (Sweden)

    Romina Hernández-Salinas


    Full Text Available BACKGROUND: Metabolic syndrome is a growing worldwide health problem. We evaluated the effects of wine grape powder (WGP, rich in antioxidants and fiber, in a rat model of metabolic syndrome induced by a high fructose diet. We tested whether WGP supplementation may prevent glucose intolerance and decrease oxidative stress in rats fed with a high fructose diet. METHODS: Male Sprague-Dawley rats weighing 180 g were divided into four groups according to their feeding protocols. Rats were fed with control diet (C, control plus 20 % WGP (C + WGP, 50 % high fructose (HF or 50 % fructose plus 20 % WGP (HF + WGP for 16 weeks. Blood glucose, insulin and triglycerides, weight, and arterial blood pressure were measured. Homeostasis model assessment (HOMA index was calculated using insulin and glucose values. A glucose tolerance test was performed 2 days before the end of the experiment. As an index of oxidative stress, thio-barbituric acid reactive substances (TBARS level was measured in plasma and kidney, and superoxide dismutase was measured in the kidney. RESULTS: Thiobarbituric acid reactive substances in plasma and renal tissue were significantly higher when compared to the control group. In addition, the area under the curve of the glucose tolerance test was higher in HF fed animals. Furthermore, fasting blood glucose, plasma insulin levels, and the HOMA index, were also increased. WGP supplementation prevented these alterations in rats fed with the HF diet. We did not find any significant difference in body weight or systolic blood pressure in any of the groups. CONCLUSIONS: Our results show that WGP supplementation prevented hyperglycemia, insulin resistance and reduced oxidative stress in rats fed with HF diet. We propose that WGP may be used as a supplement in human food as well.

  2. Estimation of the volume of distribution of some pharmacologically important compounds from their structural descriptor

    Directory of Open Access Journals (Sweden)



    Full Text Available Quantitative structure–activity relationship (QSAR approaches were used to estimate the volume of distribution (Vd using an artificial neural network (ANN. The data set consisted of the volume of distribution of 129 pharmacologically important compounds, i.e., benzodiazepines, barbiturates, nonsteroidal anti-inflammatory drugs (NSAIDs, tricyclic anti-depressants and some antibiotics, such as betalactams, tetracyclines and quinolones. The descriptors, which were selected by stepwise variable selection methods, were: the Moriguchi octanol–water partition coefficient; the 3D-MoRSE-signal 30, weighted by atomic van der Waals volumes; the fragment-based polar surface area; the d COMMA2 value, weighted by atomic masses; the Geary autocorrelation, weighted by the atomic Sanderson electronegativities; the 3D-MoRSE – signal 02, weighted by atomic masses, and the Geary autocorrelation – lag 5, weighted by the atomic van der Waals volumes. These descriptors were used as inputs for developing multiple linear regressions (MLR and artificial neural network models as linear and non-linear feature mapping techniques, respectively. The standard errors in the estimation of Vd by the MLR model were: 0.104, 0.103 and 0.076 and for the ANN model: 0.029, 0.087 and 0.082 for the training, internal and external validation test, respectively. The robustness of these models were also evaluated by the leave-5-out cross validation procedure, that gives the statistics Q2 = 0.72 for the MLR model and Q2 = 0.82 for the ANN model. Moreover, the results of the Y-randomization test revealed that there were no chance correlations among the data matrix. In conclusion, the results of this study indicate the applicability of the estimation of the Vd value of drugs from their structural molecular descriptors. Furthermore, the statistics of the developed models indicate the superiority of the ANN over the MLR model.

  3. Prescription opioid use among addictions treatment patients: nonmedical use for pain relief vs. other forms of nonmedical use. (United States)

    Bohnert, Amy S B; Eisenberg, Anna; Whiteside, Lauren; Price, Amanda; McCabe, Sean Esteban; Ilgen, Mark A


    Differences between those who engage in nonmedical prescription opioid use for reasons other than pain relief and those who engage in nonmedical use for reasons related to pain only are not well understood. Adults in a residential treatment program participated in a cross-sectional self-report survey. Participants reported whether they used opioids for reasons other than pain relief (e.g., help sleep, improve mood, or relieve stress). Within those with past-month nonmedical opioid use (n=238), logistic regression tested differences between those who reported use for reasons other than pain relief and those who did not. Nonmedical use of opioids for reasons other than pain relief was more common (66%) than nonmedical use for pain relief only (34%), and those who used for reasons other than pain relief were more likely to report heavy use (43% vs. 11%). Nonmedical use for reasons other than pain relief was associated with having a prior overdose (odds ratio [OR]=2.54, 95% CI: 1.36-4.74) and use of heroin (OR=4.08, 95% CI: 1.89-8.79), barbiturates (OR=6.44, 95% CI: 1.47, 28.11), and other sedatives (OR=5.80, 95% CI: 2.61, 12.87). Individuals who reported nonmedical use for reasons other than pain relief had greater depressive symptoms (13.1 vs. 10.5) and greater pain medication expectancies across all three domains (pleasure/social enhancement, pain reduction, negative experience reduction). Among patients in addictions treatment, individuals who report nonmedical use of prescription opioids for reasons other than pain relief represent an important clinical sub-group with greater substance use severity and poorer mental health functioning. Published by Elsevier Ltd.

  4. Pharmacological modification of sodium channels from the human heart atrium in planar lipid bilayers: electrophysiological characterization of responses to batrachotoxin and pentobarbital. (United States)

    Wartenberg, H C; Wartenberg, J P; Urban, B W


    To investigate the effects of barbiturates on batrachotoxin-modified sodium channels from different regions of the human heart. Single sodium channels from human atria were studied and compared with existing data from the human ventricle and from the central nervous system. Sodium channels from preparations of human atrial muscle were incorporated into planar lipid bilayers in the presence of batrachotoxin, a sodium channel activator. The steady-state behaviour of single sodium channels was recorded in symmetrical 500 mmol NaCl before and after the addition of pentobarbital 0.34-1.34 mmol. The batrachotoxin-treated human atrial sodium channel had an average single-channel conductance of 23.8 +/- 1.6 pS in symmetrical 500 mmol NaCl and a channel fractional open time of 0.83 +/- 0.06. The activation mid-point potential was -98.0 +/- 2.3 mV. Extracellular tetrodotoxin (a specific sodium channel blocking agent) blocked these channels with a k(1/2) = 0.53 micromol at 0 mV. Pentobarbital reduced the time average conductance of single atrial sodium channels in a concentration-dependent manner (ID50 = 0.71 mmol). In the same way, the steady-state activation was shifted to more hyperpolarized potentials (-10.6 mV at 0.67 mmol pentobarbital). The properties of batrachotoxin-modified sodium channels from human atrial tissue did not differ greatly from those described for ventricular sodium channels in the literature. Our data yielded no explanation for the observed functional diversity. However, cardiac sodium channels differ from those found in the central nervous system.

  5. Steroid modulation of the chloride ionophore in rat brain: structure-activity requirements, regional dependence and mechanism of action

    International Nuclear Information System (INIS)

    Gee, K.W.; Bolger, M.B.; Brinton, R.E.; Coirini, H.; McEwen, B.S.


    Further in vitro studies of steroids active at the gamma-aminobutyric acidA (GABAA) receptor regulated Cl- channel labeled by [35S]-t-butylbicyclophosphorothionate ([35S]TBPS) reveal additional structural requirements necessary for activity. Evaluation of selected steroids for activity against TBPS-induced convulsions show similar requirements for activity. Interestingly, steroids (e.g., 5 alpha-pregnan-3 alpha, 20 alpha-diol) were identified that have high potency but limited efficacy as modulators of [35S]TBPS binding. These characteristics are reminiscent of the clinically useful benzodiazepines (BZs) such as clonazepam. However, interactions between the prototypical anesthetic-barbiturate, sodium pentobarbital, and steroids active at the Cl- channel suggest that they do not share a common site of action as allosteric modulators of [35S]TBPS and BZ receptor binding. The most potent steroid evaluated, 5 alpha-pregnan-3 alpha-ol-20-one, modulates [35S]TBPS binding at low concentrations (IC50 approximately 17 nM) in a regionally dependent manner. All [35S]TBPS binding sites appear to be functionally coupled to a steroid modulatory site. Because several of the active steroids are metabolites of progesterone, their ability to inhibit the binding of [3H]promegestrone to the cytosolic progestin receptor in rat uterus was evaluated. Those steroids showing potent activity at the GABAA receptor-Cl- ionophore were inactive at the intracellular progestin receptor. Such specificity coupled with their high potency provide additional support for the hypothesis that some of these steroids may be involved in the homeostatic regulation of brain excitability via the GABAA-BZ receptor complex

  6. Accuracy of localizing radiopaque markers by abdominal radiography and correlation between their gastric emptying rate and that of a canned food in dogs

    International Nuclear Information System (INIS)

    Guilford, W.G.; Lawoko, C.R.O.; Allen, F.J.


    Objectives: To determine accuracy of abdominal radiography in locating radiopaque markers in the gastrointestinal tract and to assess correlation between gastric emptying rate of radiopaque markers and that of canned food. Animals: 17 healthy dogs. Procedure: Dogs were fed thirty 1.5-mm markers and ten 5-mm markers mixed in sufficient food to meet 25% of their daily caloric intake. They were then euthanatized by administration of an overdose of barbiturate at 1, 2, 5, 8, or 12 hours after eating and the abdomen was radiographed. The stomach, small intestine, and large intestine were then separated and radiographed in isolation. The wet and dry weights of the stomach contents were determined. The apparent and actual locations of the markers and the gastric emptying rates of markers, wet matter, and dry matter were compared, using rank correlation. Results: All comparisons indicated significant (P 0.92). The mean difference between the apparent and actual locations of the markers was < 3% for all comparisons. The mean difference between the percentage of small markers and large markers retained in the stomach and that of dry matter was 7.8 (SD, 6.2; range, 0 to 18)% and 11.9 (SD, 12.5; range, 0 to 44)%, respectively. Conclusions: The gastric emptying and orocolic transit rates of the markers were accurately predicted by abdominal radiography. The gastric emptying rate of the diet and the small markers and, to a lesser extent, the large markers was closely correlated. Clinical Relevance: When fed with a special canned food diet, radiopaque markers can be used to assess the gastric emptying rate of food with sufficient accuracy for clinical purposes

  7. Dose-response relationship between alcohol use and blood pressure among drivers of commercial vehicles in Calabar, Southern Nigeria

    Directory of Open Access Journals (Sweden)

    Segun Bello


    Full Text Available Alcohol is a sedative/hypnotic with effects similar to those of barbiturates.1 The type of alcoholic beverages consumed depends on the social context and financial capability. Alcoholic beverages may be in form of beer, wine, dry gin. Drinking alcohol is an activity that many people enjoy; taking a few drinks occasionally is generally harmless. Most people do not have problems as a result of drinking alcohol in this manner, although this may predispose to heavy use. Heavy alcohol consumption has been shown in observational studies to have a strong positive association with elevated blood pressure.2-4 Further evidence have been shown by clinical trials5,6 that have demonstrated that reduction in alcohol intake among individuals who drink heavily (i.e. three or more drinks per day can lower blood pressure in normotensive and hypertensive men. Some studies have recorded a linear dose-response relationship sometimes starting with a consumption threshold of three drinks per day (30 g of ethanol.7-13 In others, the relationship has been non-linear especially in women, and some authors have speculated that ingestion of small quantities may reduce blood pressure.14-22 These discrepancies may reflect differences in investigational design, methods and populations.23 Many studies have been done in this area in developed countries like the United States, United Kingdom and Australia. This is however, not a commonly researched area in this part of the world. The aim of this study was to assess the relationship between alcohol consumption and blood pressure of drivers of commercial vehicles.

  8. Pilot study of the efficacy and safety of lettuce seed oil in patients with sleep disorders

    Directory of Open Access Journals (Sweden)

    Yakoot M


    Full Text Available Mostafa Yakoot1, Sherine Helmy2, Kamal Fawal31Green Clinic Research Center, 2Pharco Pharmaceutical Company, 3Mamorah Psychiatric Hospital, Alexandria, EgyptBackground: Lactuca sativa (garden lettuce is a popular salad herb. It has been in use in folk medicine since ancient times as both an appetite stimulant and as an aid to sleep. L. sativa seed oil (Sedan® has demonstrated a pronounced sedative effect and potentiated the hypnotic effect of barbiturates in animal models. It also exhibited significant analgesic and anti-inflammatory activities. In this study, we evaluated the sedative and hypnotic effects of L. sativa in patients suffering from insomnia.Methods: Sixty patients suffering from insomnia with or without anxiety were randomized to receive capsules containing L. sativa seed oil 1000 mg (n = 30 or placebo (n = 30. All patients were asked to complete a verbal questionnaire before the start of the trial and 1 week after starting treatment.Results: Improvements in the modified State-Trait Anxiety Inventory and the Sleep rating scale scores were significantly greater in patients receiving L. sativa seed oil compared with those on placebo (P < 0.05. No side effects were found to be attributable to L. sativa seed oil at the given dosage.Conclusion: L. sativa seed oil was found to be a useful sleeping aid and may be a hazard-free line of treatment, especially in geriatric patients suffering from mild-to-moderate forms of anxiety and sleeping difficulties.Keywords: Lactuca sativa seed oil, insomnia, sleeping disorder, anxiety

  9. Relationship between alcohol drinking and aspartate aminotransferase:alanine aminotransferase (AST:ALT) ratio, mean corpuscular volume (MCV), gamma-glutamyl transpeptidase (GGT), and apolipoprotein A1 and B in the U.S. population. (United States)

    Liangpunsakul, Suthat; Qi, Rong; Crabb, David W; Witzmann, Frank


    The misuse of alcohol, even at levels just above two drinks per day, is a public health problem, but identifying patients with this potentially unhealthy drinking is hindered by the lack of tests. Several blood tests, such as those testing for gamma-glutamyl transpeptidase (GGT) or mean corpuscular volume (MCV), are among the commonly used markers to identify very heavy drinking, but combinations of these markers have rarely been tested in lighter drinkers. We examined the relationship between alcohol drinking and the levels of these markers in a national population-based study composed primarily of lighter drinkers. Data were analyzed from 8,708 adult participants in the third U.S. National Health and Nutrition Examination Survey after excluding subjects with iron overload; with hepatitis B and C; who were pregnant; and who were taking prescription drugs such as phenytoin (Dilantin), barbiturates, and hydroxyurea (Droxia and Hydrea). The relationship between the amount of alcohol drinking and GGT, aspartate aminotransferase:alanine aminotransferase ratio, MCV of erythrocytes, and apolipoprotein A1 and B were analyzed and adjusted for potential liver injury risk factors. The prevalence of unhealthy alcohol drinking (defined as consumption of more than two standard drinks per day) was 6.7%. Heavier drinkers tended to be younger and reported an average of 4.2 drinks per day. When tested alone or in combination, the sensitivity and positive predictive values for these blood tests were too low to be clinically useful in identifying the subjects in the heavier drinking category. In this large, national, population-based study, the markers of heavy drinking studied here, either alone or in combination, did not appear to be useful in identifying unhealthy drinking. More work is needed to find the novel marker(s) associated with risky alcohol drinking.

  10. Relationship Between Alcohol Drinking and Aspartate Aminotransferase:Alanine Aminotransferase (AST:ALT) Ratio, Mean Corpuscular Volume (MCV), Gamma-Glutamyl Transpeptidase (GGT), and Apolipoprotein A1 and B in the U.S. Population* (United States)

    Liangpunsakul, Suthat; Qi, Rong; Crabb, David W.; Witzmann, Frank


    Objective: The misuse of alcohol, even at levels just above two drinks per day, is a public health problem, but identifying patients with this potentially unhealthy drinking is hindered by the lack of tests. Several blood tests, such as those testing for gamma-glutamyl transpeptidase (GGT) or mean corpuscular volume (MCV), are among the commonly used markers to identify very heavy drinking, but combinations of these markers have rarely been tested in lighter drinkers. We examined the relationship between alcohol drinking and the levels of these markers in a national population-based study composed primarily of lighter drinkers. Method: Data were analyzed from 8,708 adult participants in the third U.S. National Health and Nutrition Examination Survey after excluding subjects with iron overload; with hepatitis B and C; who were pregnant; and who were taking prescription drugs such as phenytoin (Dilantin), barbiturates, and hydroxyurea (Droxia and Hydrea). The relationship between the amount of alcohol drinking and GGT, aspartate aminotransferase:alanine aminotransferase ratio, MCV of erythrocytes, and apolipoprotein A1 and B were analyzed and adjusted for potential liver injury risk factors. Results: The prevalence of unhealthy alcohol drinking (defined as consumption of more than two standard drinks per day) was 6.7%. Heavier drinkers tended to be younger and reported an average of 4.2 drinks per day. When tested alone or in combination, the sensitivity and positive predictive values for these blood tests were too low to be clinically useful in identifying the subjects in the heavier drinking category. Conclusions: In this large, national, population-based study, the markers of heavy drinking studied here, either alone or in combination, did not appear to be useful in identifying unhealthy drinking. More work is needed to find the novel marker(s) associated with risky alcohol drinking. PMID:20230722

  11. Controlling Access to Suicide Means (United States)

    Sarchiapone, Marco; Mandelli, Laura; Iosue, Miriam; Andrisano, Costanza; Roy, Alec


    Background: Restricting access to common means of suicide, such as firearms, toxic gas, pesticides and other, has been shown to be effective in reducing rates of death in suicide. In the present review we aimed to summarize the empirical and clinical literature on controlling the access to means of suicide. Methods: This review made use of both MEDLINE, ISI Web of Science and the Cochrane library databases, identifying all English articles with the keywords “suicide means”, “suicide method”, “suicide prediction” or “suicide prevention” and other relevant keywords. Results: A number of factors may influence an individual’s decision regarding method in a suicide act, but there is substantial support that easy access influences the choice of method. In many countries, restrictions of access to common means of suicide has lead to lower overall suicide rates, particularly regarding suicide by firearms in USA, detoxification of domestic and motor vehicle gas in England and other countries, toxic pesticides in rural areas, barriers at jumping sites and hanging, by introducing “safe rooms” in prisons and hospitals. Moreover, decline in prescription of barbiturates and tricyclic antidepressants (TCAs), as well as limitation of drugs pack size for paracetamol and salicylate has reduced suicides by overdose, while increased prescription of SSRIs seems to have lowered suicidal rates. Conclusions: Restriction to means of suicide may be particularly effective in contexts where the method is popular, highly lethal, widely available, and/or not easily substituted by other similar methods. However, since there is some risk of means substitution, restriction of access should be implemented in conjunction with other suicide prevention strategies. PMID:22408588


    Hydzik, Piotr; Krośniak, Mirosław; Francik, Renata; Gomółka, Ewa; Ebru, Ebru Derici; Zagrodzki, Paweł


    There is a great diversity of the acute drugs overdose cases in clinical toxicology. Clinical situation is complicated by the coexistence of factors predisposing to the development of adverse drug reactions (chronic use of drugs, polypharmacy, alcohol or drugs dependence, nutritional disorders) and by the presence of chronic organ damage, especially the liver and the kidney. The aim of this study was to evaluate whether there are sensitive plasma markers belonging to the antioxidant system in patients exposed to various xenobiotics. We measured the activity of antioxidant parameters: catalase (CAT), glutathione peroxidase (GPX3), glutathione (GSH), sulfhydryl groups (-SH), carbonyl groups (=CO) and free radicals (2,2-diphenyl-1-picrylhydrazyl, DPPH, assay) in serum of 49 patients with acute intoxication caused by carbamazepine (CBZ, n = 9), mixed drug intoxication (MDI) (n = 9), alcohol withdrawal syndrome (AWS, n = 9), acetaminophen (APAP, n = 7), tricyclic antidepressants (TCAs) (n = 5), valproic acids (VA, n = 4), narcotics (N, n = 3), and three others (benzodiazepines, BZD, n = 2; barbiturates, n = 1). The results were compared with the parameters of not intoxicated patients (n = 39). All patients had lower catalase activity in comparison to the control group (41.9 ± 16.5 vs. 196.0 ± 82.2 U/mg protein, p = 0.000), while the increase of GSH level was particularly apparent only in patients with AWS (391.3 ± 257.9 μmol/mg protein) compared to the control group (171.4 ± 88.4 μmol/mg protein, p = 0.034) and to patients intoxicated with carbamazepine (152.8 ± 102.5 μmol/mg protein, p = 0.027). Some differences, but without statistical significance, were also observed in GPX3 activity between different groups of poisoned patients.

  13. Apigenin-induced nitric oxide production involves calcium-activated potassium channels and is responsible for antiangiogenic effects. (United States)

    Erdogan, A; Most, A K; Wienecke, B; Fehsecke, A; Leckband, C; Voss, R; Grebe, M T; Tillmanns, H; Schaefer, C A; Kuhlmann, C R W


    The dietary flavonoid apigenin (Api) has been demonstrated to exert multiple beneficial effects upon the vascular endothelium. The aim of this study was to examine whether Ca(2+)-activated K(+) channels (K(Ca)) are involved in endothelial nitric oxide (NO) production and antiangiogenic effects. Endothelial NO generation was monitored using a cyclic guanosine monophosphate radioimmunoassay. K(Ca) activity and changes of the intracellular Ca(2+) concentration [Ca(2+)](i) were analyzed using the fluorescent dyes bis-barbituric acid oxonol, potassium-binding benzofuran isophthalate, and fluo-3. The endothelial angiogenic parameters measured were cell proliferation, [(3)H]-thymidine incorporation, and cell migration (scratch assay). Akt phosphorylation was examined using immunohistochemistry. Api caused a concentration-dependent increase in cyclic guanosine monophosphate levels, with a maximum effect at a concentration of 1 mum. Api-induced hyperpolarization was blocked by the small and large conductance K(Ca) inhibitors apamin and iberiotoxin, respectively. Furthermore, apamin and iberiotoxin blocked the late, long-lasting plateau phase of the Api-induced biphasic increase of [Ca(2+)](i). Inhibition of Ca(2+) signaling and the K(Ca) blockade both blocked NO production. Prevention of all three (NO, Ca(2+), and K(Ca) signaling) reversed the antiangiogenic effects of Api under both basal and basic fibroblast growth factor-induced culture conditions. Basic fibroblast growth factor-induced Akt phosphorylation was also reduced by Api. Based on our experimental results we propose the following signaling cascade for the effects of Api on endothelial cell signaling. Api activates small and large conductance K(Ca), leading to a hyperpolarization that is followed by a Ca(2+) influx. The increase of [Ca(2+)](i) is responsible for an increased NO production that mediates the antiangiogenic effects of Api via Akt dephosphorylation.

  14. Lipid solubility of sedative-hypnotic drugs influences hypothermic and hypnotic responses of long-sleep and short-sleep mice. (United States)

    De Fiebre, N C; Marley, R J; Wehner, J M; Collins, A C


    The anesthetic potency of many agents, including alcohols, barbiturates and other sedative-hypnotic drugs, is influenced by lipid solubility. Previous studies from our laboratory, however, have demonstrated that genetic factors influence this relationship. We have reported that mouse lines selectively bred for differences in duration of ethanol-induced anesthesia, the long-sleep (LS) and short-sleep (SS) mice, differ in sleep-time response to water-soluble, but not lipid-soluble, sedative-hypnotic drugs. The studies described here sought to determine whether this same relationship exists for the hypothermic response produced by 17 sedative-hypnotic drugs in the LS and SS mice. Dose-response and time course relationships for hypothermic actions were determined and were compared with the dose-related anesthetic effects of the drugs. Hypothermic potencies increased along with lipid solubility for both the LS and SS mouse lines, but the rate of change differed for the two mouse lines. LS mice were more responsive to ethanol and other water-soluble drugs whereas the SS were more responsive to lipid-soluble drugs; significant correlations were obtained between lipid solubility (log P-octanol-water partition coefficient) and relative LS-SS responsiveness to both the hypothermic and hypnotic actions of the 17 test drugs. Thus, both hypnotic and hypothermic actions of sedative-hypnotic drugs are correlated with lipid solubility. Possible explanation for these correlations include greater LS central nervous system sensitivity to water-soluble drugs and LS-SS differences in distribution of lipid-soluble drugs.

  15. [Review of the new treatment guideline for major depressive disorder by the Japanese Society of Mood Disorders]. (United States)

    Ogasawara, Kazuyoshi; Ozaki, Norio


    The Japanese Society of Mood Disorders (JSMD) published the "Treatment Guideline II: Major Depressive Disorder, 2012 Ver. 1" on July 26, 2012. This guideline (GL) is the first one published by an academic society in Japan. Presently in Japan, many people have depressive symptoms, and the socioeconomic loss (suicide, absence from work, etc.) induced by this condition cannot be overlooked. Although the Japanese society, including mass media and psychiatrists, has attempted to solve this public problem, a solution has not been found. JSMD regarded diagnosis and psychiatric management of depression, among other factors, as the key to solving this problem. For example, patients who meet the DSM-IV major depressive disorder (MDD) criteria still have numerous subtypes, and they often have other psychiatric comorbidities that a diagnosis of MDD alone cannot detect. Although the process for differential diagnosis and treatment planning is indispensable, its methodology has not been necessarily shared even among psychiatrists until today. In this GL, considering the research evidence and its limitations, JSMD suggests necessary steps for appropriate information intake, diagnosis, therapeutic alliance formation, psychoeducation, and treatment modality choice in every phase (acute and continuation/maintenance). This GL also considers pharmaco-, psycho-, and electroconvulsive therapy for major depressive subtypes (mild, moderate/severe, and psychotic). Simultaneously, psychiatrists are required to be alert to the risk from diffuse and multiple prescription of benzodiazepine receptor agonists (dependence, deterioration of sleep apnea, cognitive decline, paradoxical reaction, etc.), especially barbiturates. This GL will be revised on the basis of public comments, including criticism. In the future, treatment GLs for comorbid patients, return-to-work cases, primary care physicians, psychiatric residents, and patients with depressions other than MDD (subthreshold depression

  16. A Method of Managing Severe Traumatic Brain Injury in the Absence of Intracranial Pressure Monitoring: The Imaging and Clinical Examination Protocol. (United States)

    Chesnut, Randall M; Temkin, Nancy; Dikmen, Sureyya; Rondina, Carlos; Videtta, Walter; Petroni, Gustavo; Lujan, Silvia; Alanis, Victor; Falcao, Antonio; de la Fuenta, Gustavo; Gonzalez, Luis; Jibaja, Manuel; Lavarden, Arturo; Sandi, Freddy; Mérida, Roberto; Romero, Ricardo; Pridgeon, Jim; Barber, Jason; Machamer, Joan; Chaddock, Kelley


    The imaging and clinical examination (ICE) algorithm used in the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure (BEST TRIP) randomized controlled trial is the only prospectively investigated clinical protocol for traumatic brain injury management without intracranial pressure (ICP) monitoring. As the default literature standard, it warrants careful evaluation. We present the ICE protocol in detail and analyze the demographics, outcome, treatment intensity, frequency of intervention usage, and related adverse events in the ICE-protocol cohort. The 167 ICE protocol patients were young (median 29 years) with a median Glasgow Coma Scale motor score of 4 but with anisocoria or abnormal pupillary reactivity in 40%. This protocol produced outcomes not significantly different from those randomized to the monitor-based protocol (favorable 6-month extended Glasgow Outcome Score in 39%; 41% mortality rate). Agents commonly employed to treat suspected intracranial hypertension included low-/moderate-dose hypertonic saline (72%) and mannitol (57%), mild hyperventilation (adjusted partial pressure of carbon dioxide 30-35 mm Hg in 73%), and pressors to maintain cerebral perfusion (62%). High-dose hyperosmotics or barbiturates were uncommonly used. Adverse event incidence was low and comparable to the BEST TRIP monitored group. Although this protocol should produce similar/acceptable results under circumstances comparable to those in the trial, influences such as longer pre-hospital times and non-specialist transport personnel, plus an intensive care unit model of aggressive physician-intensive care by small groups of neurotrauma-focused intensivists, which differs from most high-resource models, support caution in expecting the same results in dissimilar settings. Finally, this protocol's ICP-titration approach to suspected intracranial hypertension (vs. crisis management for monitored ICP) warrants further study.

  17. Detection in superheated water chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Chienthavorn, O


    Superheated water has been used successfully as an eluent in liquid chromatography and has been coupled to various modes of detection, ultraviolet (UV), fluorescence, and nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). A number of compounds were examined on poly(styrene-divinylbenzene) (PS-DVB), polybutadiene (PBD), and octadecylsilyl bonded silica (ODS) column with isothermal and temperature programmes. The PS-DVB column was mostly used throughout the project as it was the most stable. Not only pure water could serve as superheated water mobile phase; inorganic buffered water and ion-pairing reagent with a concentration of 1-3 mM of the buffer and reagent were also exploited. It was shown that the pH could be controlled during the separation without salt precipitation and the separations followed a conventional reversed-phase HPLC method. Results from fluorescence detection showed good separation of a series of vitamins, such as pyridoxine, riboflavin, thiamine, and some analgesics. The relationship of riboflavin using the detection was linear and the detection limit was seven times higher than that of a conventional method. Simultaneous separation and identification using superheated water chromatography-NMR was demonstrated. With using a stop flow method, NMR spectra of model drugs, namely barbiturates, paracetamol, caffeine and phenacetin were obtained and the results agreed with reference spectra, confirming a perfect separation. A demonstration to obtain COSY spectrum of salicylamide was also performed. The method was expanded to the coupling of superheated water LC to NMR-MS. Results from the hyphenated detection method showed that deuteration and degradation happened in the superheated water conditions. The methyl group hydrogens of pyrimidine ring of sulfonamide and thiamine were exchanged with deuterium. Thiamine was decomposed to 4-methyl-5-thiazoleethanol and both were deuterated under the conditions. (author)

  18. Controlling Access to Suicide Means

    Directory of Open Access Journals (Sweden)

    Miriam Iosue


    Full Text Available Background: Restricting access to common means of suicide, such as firearms, toxic gas, pesticides and other, has been shown to be effective in reducing rates of death in suicide. In the present review we aimed to summarize the empirical and clinical literature on controlling the access to means of suicide. Methods: This review made use of both MEDLINE, ISI Web of Science and the Cochrane library databases, identifying all English articles with the keywords “suicide means”, “suicide method”, “suicide prediction” or “suicide prevention” and other relevant keywords. Results: A number of factors may influence an individual’s decision regarding method in a suicide act, but there is substantial support that easy access influences the choice of method. In many countries, restrictions of access to common means of suicide has lead to lower overall suicide rates, particularly regarding suicide by firearms in USA, detoxification of domestic and motor vehicle gas in England and other countries, toxic pesticides in rural areas, barriers at jumping sites and hanging, by introducing “safe rooms” in prisons and hospitals. Moreover, decline in prescription of barbiturates and tricyclic antidepressants (TCAs, as well as limitation of drugs pack size for paracetamol and salicylate has reduced suicides by overdose, while increased prescription of SSRIs seems to have lowered suicidal rates. Conclusions: Restriction to means of suicide may be particularly effective in contexts where the method is popular, highly lethal, widely available, and/or not easily substituted by other similar methods. However, since there is some risk of means substitution, restriction of access should be implemented in conjunction with other suicide prevention strategies.

  19. Controlling access to suicide means. (United States)

    Sarchiapone, Marco; Mandelli, Laura; Iosue, Miriam; Andrisano, Costanza; Roy, Alec


    Restricting access to common means of suicide, such as firearms, toxic gas, pesticides and other, has been shown to be effective in reducing rates of death in suicide. In the present review we aimed to summarize the empirical and clinical literature on controlling the access to means of suicide. This review made use of both MEDLINE, ISI Web of Science and the Cochrane library databases, identifying all English articles with the keywords "suicide means", "suicide method", "suicide prediction" or "suicide prevention" and other relevant keywords. A number of factors may influence an individual's decision regarding method in a suicide act, but there is substantial support that easy access influences the choice of method. In many countries, restrictions of access to common means of suicide has lead to lower overall suicide rates, particularly regarding suicide by firearms in USA, detoxification of domestic and motor vehicle gas in England and other countries, toxic pesticides in rural areas, barriers at jumping sites and hanging, by introducing "safe rooms" in prisons and hospitals. Moreover, decline in prescription of barbiturates and tricyclic antidepressants (TCAs), as well as limitation of drugs pack size for paracetamol and salicylate has reduced suicides by overdose, while increased prescription of SSRIs seems to have lowered suicidal rates. Restriction to means of suicide may be particularly effective in contexts where the method is popular, highly lethal, widely available, and/or not easily substituted by other similar methods. However, since there is some risk of means substitution, restriction of access should be implemented in conjunction with other suicide prevention strategies.

  20. Medicare Part D research highlights and policy updates, 2013: impact and insights. (United States)

    Stubbings, JoAnn; Lau, Denys T


    Since its implementation in 2006, Medicare Part D has evolved from a program that offered basic access to covered drugs for beneficiaries to one that has the potential to affect patient outcomes. The purpose of this article was to highlight key research findings on Medicare Part D published in 2012 and major public policy initiatives for Part D for 2013. PubMed/MEDLINE was searched for research studies on Part D published in 2012 in biomedical/scientific, peer-reviewed, English-language journals. For policy updates, sources included the Federal Register, the 2013 Final Call Letter, guidance from the Centers for Medicare and Medicaid Services, and 2012 publications on Part D policy identified in PubMed. Part D has been associated with higher medication use and lower out-of-pocket (OOP) costs of many long-term medications; however, differences within subgroups of beneficiaries have been observed. Studies on health outcomes have been inconclusive. Part D policy changes in 2013 have addressed problems with the benefit, namely coverage of benzodiazepines and barbiturates; reducing coinsurance in the coverage gap; reducing fraud, waste, and abuse; medication therapy management program standardization; and an expanded appeals process. Research continues to suggest that Part D is effective in increasing medication utilization and lowering OOP costs. Further work is needed to clarify the effects of Part D on nondrug health care service utilization and health outcomes. Policy changes for 2013 addressed specific improvements in the Medicare Part D benefit while potentially generating cost-savings for Medicare and Medicaid. Future challenges include alleviating access burden to medications during the phase-out of the coverage gap, minimizing disparities among Part D beneficiaries, and coordinating the Part D benefit with Medicare parts A and B via Medicare Accountable Care Organizations. A more integrated and coordinated Medicare benefit among all of its components would

  1. Allosteric ligands and their binding sites define γ-aminobutyric acid (GABA) type A receptor subtypes. (United States)

    Olsen, Richard W


    GABAA receptors (GABA(A)Rs) mediate rapid inhibitory transmission in the brain. GABA(A)Rs are ligand-gated chloride ion channel proteins and exist in about a dozen or more heteropentameric subtypes exhibiting variable age and brain regional localization and thus participation in differing brain functions and diseases. GABA(A)Rs are also subject to modulation by several chemotypes of allosteric ligands that help define structure and function, including subtype definition. The channel blocker picrotoxin identified a noncompetitive channel blocker site in GABA(A)Rs. This ligand site is located in the transmembrane channel pore, whereas the GABA agonist site is in the extracellular domain at subunit interfaces, a site useful for low energy coupled conformational changes of the functional channel domain. Two classes of pharmacologically important allosteric modulatory ligand binding sites reside in the extracellular domain at modified agonist sites at other subunit interfaces: the benzodiazepine site and the high-affinity, relevant to intoxication, ethanol site. The benzodiazepine site is specific for certain GABA(A)R subtypes, mainly synaptic, while the ethanol site is found at a modified benzodiazepine site on different, extrasynaptic, subtypes. In the transmembrane domain are allosteric modulatory ligand sites for diverse chemotypes of general anesthetics: the volatile and intravenous agents, barbiturates, etomidate, propofol, long-chain alcohols, and neurosteroids. The last are endogenous positive allosteric modulators. X-ray crystal structures of prokaryotic and invertebrate pentameric ligand-gated ion channels, and the mammalian GABA(A)R protein, allow homology modeling of GABA(A)R subtypes with the various ligand sites located to suggest the structure and function of these proteins and their pharmacological modulation. © 2015 Elsevier Inc. All rights reserved.

  2. Central effects of isolated fractions from the root of Petiveria alliacea L. (tipi) in mice. (United States)

    Gomes, Patrícia B; Noronha, Emmanuelle C; de Melo, Carla Thiciane V; Bezerra, José N S; Neto, Manoel A; Lino, Cleide S; Vasconcelos, Silvânia M M; Viana, Glauce S B; de Sousa, Francisca Cléa F


    Petiveria alliacea L. (tipi) a shrub from Phytolaccaceae family is popularly used in folk medicine for treating a wide variety of disorders in South and Central America. To investigate the neuropharmacological properties on experimental animals. The acetate (FA), hexanic (FH), hydroalcoholic (FHA) and precipitated hydroalcoholic (FHAppt) fractions from the root of tipi were studied to investigate its pharmacological properties in the classical behavioral models (open-field, elevated plus maze-EPM, rotarod, barbiturate-induced sleeping time, forced swimming and pentylenetetrazole (PTZ)-induced convulsions tests) using mice. These fractions were administered intraperitoneally and orally to female mice at single doses of 100 and 200mg/kg. All these fractions decreased the locomotor activity, rearing and grooming in the open-field test, suggesting a possible central depressant action. No significant effect was evident on motor coordination of the animals in the rotarod test. On EPM, all the fractions of tipi presented a significant reduction on the time of permanence in the open arms, indicating an absence of anxiolytic-like effect. In addition, the fractions increased the immobility time in the forced swimming test and potentiated pentobarbital-induced sleeping time in mice, confirmed a probable sedative and central depressant effect. Furthermore, the fractions increased the latency to the first convulsion and the lethal time of the PTZ-induced convulsions test in the animals, confirmed its popular use as anticonvulsant. Our results suggest that the fractions of P. alliacea L. contains biologically active substance(s) that might be acting in the CNS and have significant depressant and anticonvulsant potentials, supporting folk medicine use of this plant.

  3. The effect of central nervous system depressant, stimulant and hallucinogenic drugs on injury severity in patients admitted for trauma. (United States)

    Cordovilla-Guardia, Sergio; Lardelli-Claret, Pablo; Vilar-López, Raquel; López-Espuela, Fidel; Guerrero-López, Francisco; Fernández-Mondéjar, Enrique


    The effect of drugs other than alcohol on severity of trauma remains unclear. Pooled data analyses in previous studies that grouped substances with opposite effects on the central nervous system (CNS) may have masked the influence of substances on injury severity. The aim was to analyze the effect of stimulant, hallucinogenic and depressant drugs other than alcohol on injury severity in trauma patients. The presence of alcohol, stimulant drugs (cocaine, amphetamines and methamphetamines), depressant drugs (benzodiazepines, opiates, methadone and barbiturates) and hallucinogenic drugs (THC and PCP) was analyzed in 1187 patients between 16 and 70 years old admitted to a trauma hospital between November 2012 and June 2015. Injury severity was determined prospectively as the Injury Severity Score. A multivariate analysis was used to quantify the strength of association between exposure to substances and trauma severity, using the presence of alcohol as a stratification variable. Drugs other than alcohol were found in 371 patients (31.3%): 32 (2.7%) stimulants, 186 (15.3%) depressants, 78 (6.6%) hallucinogenics and 75 (5.6%) polydrug use. The presence of CNS depressant substances was associated with increased injury severity only in patients also exposed to alcohol, with an adjusted odds ratio of 4.63 (1.37-15.60) for moderate injuries and 7.83 (2.53-24.21) for severe. CNS depressant drugs had a strong influence on injury severity in patients who screened positive for alcohol consumption. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Receptor studies in biological psychiatry

    International Nuclear Information System (INIS)

    Fujiwara, Yutaka


    Recent advances in the pharmacological treatment of endogenous psychosis have led to the development of biological studies in psychiatry. Studies on neurotransmitter receptors were reviewed in order to apply positron-emission tomograph (PET) for biological psychiatry. The dopamine (DA) hypothesis for schizophrenia was advanced on the basis of the observed effects of neuroleptics and methamphetamine, and DA(D 2 ) receptor supersensitivity measured by PET and receptor binding in the schizophrenic brain. The clinical potencies of neuroleptics for schizophrenia were correlated with their abilities to inhibit the D 2 receptor, and not other receptors. The σ receptor was expected to be a site of antipsychotic action. However, the potency of drugs action on it was not correlated with clinical efficacy. Haloperidol binds with high affinity to the σ receptor, which may mediate acute dystonia, an extrapyramidal side effect of neuroleptics. Behavioral and neurochemical changes induced by methamphetamine treatment were studied as an animal model of schizophrenia, and both a decrease of D 2 receptor density and an increase of DA release were detected. The monoamine hypothesis for manic-depressive psychosis was advanced on the basis of the effect of reserpine, monoamine oxidase inhibitor and antidepressants. 3 H-clonidine binding sites were increased in platelet membranes of depressive patients, 3 H-imipramine binding sites were decreased. The GABA A receptor is the target site for the action of anxiolytics and antiepileptics such as benzodiazepines and barbiturates. Recent developments in molecular biology techniques have revealed the structure of receptor proteins, which are classified into two receptor families, the G-protein coupled type (D 2 ) and the ion-channel type (GABA A ). (J.P.N.)

  5. Tagetes lucida Cav.: Ethnobotany, phytochemistry and pharmacology of its tranquilizing properties. (United States)

    Pérez-Ortega, G; González-Trujano, M E; Ángeles-López, G E; Brindis, F; Vibrans, H; Reyes-Chilpa, R


    Morelos State is one of the most important regions of Mexico where several plant species are used in traditional medicine to influence central nervous system (CNS) activity; for example Tagetes lucida Cav. To investigate the ethnobotany, phytochemistry and pharmacology of the tranquilizing properties of T. lucida aerial parts. Data on the medicinal uses of T. lucida were explored by interviewing healers and merchants of local markets in different regions of Morelos State by using a questionnaire. Anxiolytic and/or sedative-like responses of the T. lucida were investigated in experimental models in mice such as: open-field, exploration cylinder, hole-board, plus-maze, and the barbituric-induced hypnosis potentiation. The possible mechanism of action was explored in the presence of WAY100635 (0.32mg/kg, i.p.) and flumazenil (10mg/kg, i.p.) antagonists. A feasible active compound was isolated and identified by using conventional chromatography, including UHPLC and MS (DART) [M+H]+ techniques. Interviews of healers and merchants from ten local regions of Morelos State showed that they recommended T. lucida as infusion and as tincture for several culture-bound syndromes associated with the CNS. Anxiolytic and sedative-like activities of polar extracts were corroborated in the experimental models; these effects were inhibited in the presence of 5-HT1A and GABA/BDZ receptor antagonists. Dimethylfraxetin was identified as one possible active compound. The results support the anxiolytic and sedative-like properties of T. lucida in traditional medicine by involving serotonergic and GABAergic neurotransmission and coumarinic constituents. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Cyanuric acid hydrolase from Azorhizobium caulinodans ORS 571: crystal structure and insights into a new class of Ser-Lys dyad proteins.

    Directory of Open Access Journals (Sweden)

    Seunghee Cho

    Full Text Available Cyanuric acid hydrolase (CAH catalyzes the hydrolytic ring-opening of cyanuric acid (2,4,6-trihydroxy-1,3,5-triazine, an intermediate in s-triazine bacterial degradation and a by-product from disinfection with trichloroisocyanuric acid. In the present study, an X-ray crystal structure of the CAH-barbituric acid inhibitor complex from Azorhizobium caulinodans ORS 571 has been determined at 2.7 Å resolution. The CAH protein fold consists of three structurally homologous domains forming a β-barrel-like structure with external α-helices that result in a three-fold symmetry, a dominant feature of the structure and active site that mirrors the three-fold symmetrical shape of the substrate cyanuric acid. The active site structure of CAH is similar to that of the recently determined AtzD with three pairs of active site Ser-Lys dyads. In order to determine the role of each Ser-Lys dyad in catalysis, a mutational study using a highly sensitive, enzyme-coupled assay was conducted. The 10⁹-fold loss of activity by the S226A mutant was at least ten times lower than that of the S79A and S333A mutants. In addition, bioinformatics analysis revealed the Ser226/Lys156 dyad as the only absolutely conserved dyad in the CAH/barbiturase family. These data suggest that Lys156 activates the Ser226 nucleophile which can then attack the substrate carbonyl. Our combination of structural, mutational, and bioinformatics analyses differentiates this study and provides experimental data for mechanistic insights into this unique protein family.

  7. Effect of proton pump inhibitors on gastric pH in patients exposed to severe stress. (United States)

    Lenz, Kurt; Buder, Robert; Firlinger, Fritz; Lohr, Gerald; Voglmayr, Martin


    The incidence of upper gastrointestinal bleeding from stress ulcers has decreased within the last 30 years. Improvements in intensive care medicine including advanced equipment for artificial ventilation, better sedoanalgesic therapies, and the use of stress ulcer prophylaxis are credited for the decline. To determine the effectiveness of proton pump inhibitors (PPIs) on gastric pH in patients exposed to a defined severe stress situation during a specified time period. Prospective open study in a tertiary community hospital. A high dose (80 mg bolus followed by 8 mg/h) of either pantoprazol or omeprazol was infused in 17 patients with opiate dependence who were undergoing ultra-rapid opiate withdrawal by barbiturate anesthesia. Gastric pH. Gastric pH did not change significantly in the majority of patients (mean pH 1.2 ± 0.9 immediately before, 1.5 ± 1.6 at 60 min after, and 1.3 ± 1.5 at 120 min after PPI infusion began). Gastric pH increased temporarily in two of the nine patients receiving omeprazol. In two of the eight patients, pantoprazol led to a late but sustained increase in gastric pH (pH 3.9 and 6.0 at 120 min post infusion). High doses of PPIs are ineffective in elevating gastric pH in patients exposed to severe stress such as ultra-rapid opiate detoxification. Therefore, adequate sedoanalgesia might be the main factor responsible for preventing stress-related bleeding in critically ill patients.

  8. Modulation of GABAA Receptors in the Treatment of Epilepsy. (United States)

    Palma, Eleonora; Ruffolo, Gabriele; Cifelli, Pierangelo; Roseti, Cristina; Vliet, Erwin A van; Aronica, Eleonora


    A variety of evidence suggested that an imbalance in excitatory and inhibitory neurotransmission could be one of the pathophysiological mechanisms underlying the occurrence and progression of seizures. Understanding the causes of this imbalance may provide essential insight into the basic mechanisms of epilepsy and may uncover novel targets for future drug therapies. Accordingly, GABA is the most important inhibitory neurotransmitter in the CNS and its receptors (e.g., GABAARs) can still be relevant targets of new antiepileptic drugs (AEDs). Up to now, a variety of modulating agents that directly or indirectly act at GABAARs have been proposed for restoring the physiological balance of excitation and inhibition in the epileptogenic brain. While benzodiazepine, barbiturates and allosteric modulators of GABAARs are well-known for their anticonvulsant effect, new compounds as modulators of chloride homeostasis or phytocannabinoids are not completely unraveled and their antiepileptic action is still matter of debate. In addition, several inflammatory mediators as cytokines and chemokines play an important role in the modulation of GABAAR function, even if further research is needed to translate these new findings from the bench to the bedside. Finally yet importantly, a new frontier in epilepsy research is represented by the observation that specific small noncoding RNAs, namely miRNAs, may regulate GABAAR function paving the road to therapeutic approaches based on the modulation of gene expression. Here, we review key physiological, neuropathological and functional studies that altogether strengthen the role of modulation of GABAARs function as therapeutic target. The discovery of the novel molecular mechanisms underlying the GABAergic transmission in epilepsy represents another heavy piece in the "epileptic puzzle". Even if GABAAR is an old story in the pharmacology of the epilepsy, the reviewed findings suggest that new players in the scenario need to be considered

  9. Prevention and treatment of intracranial hypertension. (United States)

    Jantzen, Jan-Peter A H


    Hg), barbiturate coma or experimental protocols such as tris buffer, indomethacin or induced hypothermia. The last resort is emergent bilateral decompressive craniectomy; once taken into consideration, it should be performed without undue delay.

  10. Stanley L Drummond-Jackson. Pioneer of intravenous anaesthesia in dentistry. (United States)

    Gopakumar, Ashish; Gopakumar, V


    Stanley Lithgow Drummond-Jackson was born in Northumberland and qualified from Edinburgh University Dental School in 1931. Even in the early stages of his practice he devoted his energies to the problem of pain control in dentistry, publishing his first paper in 1935. In the early 20th century most dental anaesthetics were inhalational with nitrous oxide, ether, ethyl chloride and chloroform. The introduction of intravenous hexobarbitone in 1931 led to bold and enthusiastic researchers like Drummond-Jackson to pioneer its use in dental practice. He published his major work on intravenous hexobarbitone in 1952. In 1957, Drummond-Jackson and a group of colleagues formed the now well-known organisation called 'Society for the Advancement of Anaesthesia in Dentistry' or SAAD. SAAD has grown from a group of 40 to over 4000 members worldwide. In 1969, the BMJ published an article condemning Drummond-Jackson's technique of intermittent intravenous methohexitone. At his personal expense, Drummond-Jackson brought a libel action against the BMJ and authors of this paper. There were no winners as the case was settled after 38 days and earned the reputation for being the longest and most expensive libel case in the history of the London Courts. Despite this setback the founder of SAAD devoted the last days of his life in research, teaching and abolishing fear and pain in dentistry. He gained international reputation as a teacher in dental anaesthesia and was honoured with fellowships and awards. He died in 1975 at the age of 66. In the early 1900s dental anaesthesia was only inhalational with mainly nitrous oxide on one hand and ether, ethyl chloride and chloroform on the other. Induction was at times stormy and prolonged and recovery was delayed. The synthesis of barbiturates, especially intravenous hexobarbitone (1931), thiopentone (1932) and methohexitone (1959) opened new avenues for dental anaesthesia. Modern anaesthesia owes a lot to early pioneers, many of them being

  11. Associations between community attachments and adolescent substance use in nationally representative samples. (United States)

    Wray-Lake, Laura; Maggs, Jennifer L; Johnston, Lloyd D; Bachman, Jerald G; O'Malley, Patrick M; Schulenberg, John E


    Social capital and social attachment theories of substance use argue that positive bonds to society and the conventional values they promote deter adolescents from substance use. Using nationally representative samples of U.S. high school seniors, we hypothesized that adolescents' community attachments, measured by social trust, social responsibility, and religiosity, would be negatively associated with lifetime and 30-day substance use. We used repeated cross-sectional nationally representative high school senior data from 1976 to 2008 Monitoring the Future Study cohorts (weighted N = 64,246; 51.6% female). Participation rate ranged from 77% to 86% across years. A series of multiple linear and logistic regressions examined unique associations of adolescents' social trust, social responsibility, and religiosity with lifetime and 30-day use of cigarettes, alcohol, marijuana, hallucinogens, cocaine, amphetamines, barbiturates, tranquilizers, and narcotics. Models controlled for gender, race, college aspirations, high school grades, parents' education, and survey year. Social trust, social responsibility, and religiosity showed independent negative associations with use of cigarettes, alcohol, marijuana, and six other types of drugs. After accounting for controls, community attachments related to lower lifetime and past 30-day use. Associations were consistent across measures, except social responsibility was not associated with binge drinking or lifetime illicit drugs besides marijuana. Study strengths included nationally representative samples, diverse substance use measures, and inclusion of controls. We extend theory by suggesting that distinct aspects of adolescents' community attachments uniquely relate to lower substance use. Results suggest potential public health benefits of integrating promotion of community attachments with substance use prevention. Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  12. Effects of body temperature, passive limb motion and level of anesthesia on the activity of the inspiratory muscles. (United States)

    D'Angelo, E


    The relationships between relative tidal activity (moving average EMG) of the diaphragm (AdiT) and of the external intercostal or parasternal muscles (AicT) and between the rate of rise of these activities (Adi and Aic) were assessed during rebreathing in rabbits with various body temperatures (BT: 34-41 degrees C) before and after vagotomy (VGT), at rest and during passive limb motion (PLM), and in vagotomized rabbits with or without thoracic dorsal rhizotomy (TDR) under light (LBA) or deep barbiturate anesthesia (DBA). Both relationships had the form AicT = a AdiTb and Aic = a' Adib'. In intact normothermic animals under LBA mean values for b and b' were 1.47 and 1.37, a and a' being unity by definition. No changes in b or b' occurred even with TDR: this suggests that the relation between the central command to phrenic and to inspiratory intercostal alpha-motoneurones was the same under all conditions. Neither BT nor PLM modified a', but a changed owing to BT and PLM dependence of the relation between central inspiratory drive and off-switch threshold. Both VGT, independently of BT, and DBA decreased a and a' before but not after TDR, when a and a' reached the lowest values (0.12 and 0.22). Hence VGT and DBA, but not BT and PLM, change the relation between the central command to inspiratory intercostal alpha- and gamma-motoneurones, the multiplicative effect of alpha-gamma linkage on AicT and Aic being prevented by TDR.

  13. Altered GABAA Receptor Subunit Expression and Pharmacology in Human Angelman Syndrome Cortex (United States)

    Roden, William H.; Peugh, Lindsey D.; Jansen, Laura A.


    The neurodevelopmental disorder Angelman syndrome is most frequently caused by deletion of the maternally-derived chromosome 15q11-q13 region, which includes not only the causative UBE3A gene, but also the β3-α5-γ3 GABAA receptor subunit gene cluster. GABAergic dysfunction has been hypothesized to contribute to the occurrence of epilepsy and cognitive and behavioral impairments in this condition. In the present study, analysis of GABAA receptor subunit expression and pharmacology was performed in cerebral cortex from four subjects with Angelman syndrome and compared to that from control tissue. The membrane fraction of frozen postmortem neocortical tissue was isolated and subjected to quantitative Western blot analysis. The ratios of β3/β2 and α5/α1 subunit protein expression in Angelman syndrome cortex were significantly decreased when compared with controls. An additional membrane fraction was injected into Xenopus oocytes, resulting in incorporation of the brain membrane vesicles with their associated receptors into the oocyte cellular membrane. Two-electrode voltage clamp analysis of GABAA receptor currents was then performed. Studies of GABAA receptor pharmacology in Angelman syndrome cortex revealed increased current enhancement by the α1-selective benzodiazepine site agonist zolpidem and by the barbiturate phenobarbital, while sensitivity to current inhibition by zinc was decreased. GABAA receptor affinity and modulation by neurosteroids were unchanged. This shift in GABAA receptor subunit expression and pharmacology in Angelman syndrome is consistent with impaired extrasynaptic but intact to augmented synaptic cortical GABAergic inhibition, which could contribute to the epileptic, behavioral, and cognitive phenotypes of the disorder. PMID:20692323

  14. Cerebral physiology and preservation during cardiac arrest Fisiología y preservación cerebral durante el paro cardíaco: vulnerabilidad del cerebro

    Directory of Open Access Journals (Sweden)

    Luis M. Gómez


    Full Text Available

    Cerebral physiology during cardiac arrest is discussed with particular Interest on selective neuronal damage. Previous concepts on brain tolerance to hypoxia are analyzed and new information about brain function prognosis after cardiac arrest is presented. Therapeutic alternatives for brain preservation are discussed with emphasis on the lack of effectiveness of barbiturates, the results of research with other drugs and the future role that blockers of excitatory neurotransmission may have as elements of cerebral preservation.

    Se hace una aproximación a la fisiología cerebral durante el paro cardíaco, destacando el concepto de darlo neuronal selectivo. Se presentan elementos que permiten modificar concepciones antiguas sobre la tolerancia del cerebro a la hipoxia severa. Además, se hace un nuevo planteamiento sobre el pronóstico cerebral luego de un paro cardíaco y se esbozan las alternativas terapéuticas utilizadas hasta la fecha para la preservación cerebral. Se hace énfasis en la inefectividad de los barbitúricos, en la investigación sobre la terapia con otras drogas y en el futuro abierto hacia los bloqueadores de los neurotransmisores excitadores, como elementos terapéuticos para la preservación cerebral.

  15. Comparison of Alcohol Withdrawal Outcomes in Patients Treated with Benzodiazepines Alone versus Adjunctive Phenobarbital: a Retrospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Lauren Z. Gashlin


    Full Text Available Background: For treatment of severe alcohol withdrawal syndrome, high dose benzodiazepines (BZDs may cause delirium and over-sedation. Phenobarbital (PBT is a long-acting barbiturate effective for the treatment of alcohol withdrawal. Given the potential benefits of PBT, we sought to investigate the effectiveness of PBT as adjunctive treatment for alcohol withdrawal. Methods: This was a retrospective cohort study on patients with a diagnosis of alcohol withdrawal who had a CIWA-Ar score > 10 treated with either BZDs alone (BZD alone group or BZDs with adjunctive PBT (PBT-adjunct group. The patients received at least one dose of PBT in addition to BZDs (variable doses in the PBT-adjunct group, and three doses of 20 mg diazepam equivalents within 6 hours in the BZD alone group. The primary endpoint was the proportion of patients with a CIWA-Ar score < 10 at 24 hours after initial treatment. Duration of withdrawal and cumulative dose of BZDs were also assessed. Results: Seven subjects in the adjunctive phenobarbital and 21 in the benzodiazepine group were included in the final analysis. Two patients (28.6% in the PBT-adjunct group and 5 patients (23.8% in the BZD only group achieved the primary endpoint, though the difference between the two groups was not statistically significant (P = 0.588. The median (IQR duration of withdrawal symptoms was 44 (12-62 hours in the PBT-adjunct group compared to 53 (37-87 hours in the BZD only group, with no significant difference between the groups (P = 0.249. The median (IQR cumulative BZD dose requirement (diazepam equivalent in the PBT-adjunct group was significantly lower than BZD alone group (25 (20-226 vs. 326 (160-550 mg, P = 0.02. Conclusion: PBT appears to be a safe and effective alternative to BZDs for the treatment of alcohol withdrawal in non-critically ill patients and may be BZD sparing.

  16. Stability of pentobarbital in soil. (United States)

    Bagsby, Chasity; Saha, Anita; Goodin, Granville; Siddiqi, Sheeba; Farone, Mary; Farone, Anthony; Kline, Paul C


    Intravenous injection of barbiturates, particularly pentobarbital (5-ethyl-5-pentan-2-yl-1,3-diazinane-2,4,5-trione), is a widely used method to euthanize large animals such as horses. However, one concern with this method is the fate of pentobarbital after the disposal of the carcass. As tissues decompose, pentobarbital may leach into the soil and from there migrate to groundwater. A method using methanol extraction, solid phase concentration, and liquid chromatography (LC/MS) has been developed to measure pentobarbital in soils. Recovery of pentobarbital from soil averaged approximately 85% from different soil types including topsoil, potting soil, sand, stall sweepings, and loam. The method was capable of detecting pentobarbital levels of 0.1 ppm. A calibration curve was constructed with a linear range of 1 ppm to 100 ppm. The limit of quantification was 0.5 ppm. The rate of degradation of pentobarbital in sand, topsoil, and potting soil was measured over a 17-week period. At the end of week 17, approximately 17% of the pentobarbital remained in the sand, 19% remained in the topsoil, and 10% remained in the potting soil. While there was a significant decrease in the pentobarbital recovered from the soil, there were still detectable amounts of pentobarbital present in the soil after 17 weeks. To determine the importance of bacterial degradation, the three soil types were autoclaved before addition of pentobarbital. After autoclaving, no degradation of pentobarbital was observed in sand and one topsoil sample, while there was no difference in the degradation of pentobarbital in autoclaved potting soil versus potting soil that had not undergone autoclaving.

  17. Effects of propofol and pentobarbital on calcium concentration in presynaptic boutons on a rat hippocampal neuron. (United States)

    Ito, Shinichi; Sugiyama, Hitomi; Kitahara, Seiko; Ikemoto, Yoshimi; Yokoyama, Takeshi


    Numerous reports suggest that intravenously administered (IV) anesthetics affect postsynaptic events in the central nervous system. However, there is little evidence about how general anesthetics influence the presynaptic processes. The level of presynaptic calcium (Ca(2+)) concentration ([Ca(2+)](pre)) regulates neurotransmitter release. In this study, we investigated the effects of anesthetic propofol IV and the barbiturate pentobarbital on neurotransmitter release by measuring [Ca(2+)](pre) in the presynaptic nerve terminals (boutons) on a dissociated single hippocampal rat neuron. Sprague-Dawley rats 10-14 days old were decapitated under pentobarbital anesthesia, and brain slices were prepared. The hippocampal CA1 area was touched with a fire-polished glass pipette, which vibrated horizontally, and neurons were dissociated, along with the attached presynaptic boutons. The presynaptic boutons were visualized under a confocal laser-scanning microscope after staining with FM1-43 dye, and [Ca(2+)](pre) was measured with acetoxymethyl ester of fluo-3 (fluo-3 AM). High potassium (K(+)) (15-90 mM) increased the [Ca(2+)](pre) in the Ca(2+)-containing solution in a concentration-dependent manner. Whereas propofol (10 μM) and pentobarbital (300 μM) suppressed the high K(+) (60 mM)-induced increase in [Ca(2+)](pre) in the boutons attached to the dendrite, they did not affect [Ca(2+)](pre) in the boutons attached to the soma or dendrite base. As a large majority of excitatory synapses are located on dendritic spines, these agents may affect Ca(2+) mobilization in the excitatory presynaptic boutons. Propofol and pentobarbital may affect neurotransmitter release from the excitatory presynaptic nerve terminals due to inhibition of increase in [Ca(2+)](pre).

  18. Bicuculline, pentobarbital and diazepam modulate spontaneous GABAA channels in rat hippocampal neurons (United States)

    Birnir, Bryndis; Eghbali, Mansoureh; Everitt, Andrea B; Gage, Peter W


    Spontaneously opening, chloride-selective channels that showed outward rectification were recorded in ripped-off patches from rat cultured hippocampal neurons and in cell-attached patches from rat hippocampal CA1 pyramidal neurons in slices. In both preparations, channels had multiple conductance states and the most common single-channel conductance varied. In the outside-out patches it ranged from 12 to 70 pS (Vp=40 mV) whereas in the cell-attached patches it ranged from 56 to 85 pS (−Vp=80 mV). Application of GABA to a patch showing spontaneous channel activity evoked a rapid, synchronous activation of channels. During prolonged exposure to either 5 or 100 μM GABA, the open probability of channels decreased. Application of GABA appeared to have no immediate effect on single-channel conductance. Exposure of the patches to 100 μM bicuculline caused a gradual decrease on the single-channel conductance of the spontaneous channels. The time for complete inhibition to take place was slower in the outside-out than in the cell-attached patches. Application of 100 μM pentobarbital or 1 μM diazepam caused 2–4 fold increase in the maximum channel conductance of low conductance (<40 pS) spontaneously active channels. The observation of spontaneously opening GABAA channels in cell-attached patches on neurons in slices suggests that they may have a role in neurons in vivo and could be an important site of action for some drugs such as benzodiazepines, barbiturates and general anaesthetics. PMID:11030718

  19. Influence of sedation and data acquisition method on tracer uptake in animal models: [{sup 123}I]-2-iodo-L-phenylalanine in pentobarbital-sedated tumor-bearing athymic mice

    Energy Technology Data Exchange (ETDEWEB)

    Kersemans, Veerle [Laboratory for Radiopharmacy, Universiteit Gent, Harelbekestraat 72 B-9000 Gent (Belgium)]. E-mail:; Spiegeleer, Bart de [Laboratory for Radiopharmacy, Universiteit Gent, Harelbekestraat 72 B-9000 Gent (Belgium); Mertens, John [Laboratory for Medical Imaging and Physics, Vrije Universiteit Brussel, Laarbecklaan 103 B-1090 Brussel (Belgium); Slegers, Guido [Laboratory for Radiopharmacy, Universiteit Gent, Harelbekestraat 72 B-9000 Gent (Belgium)


    Objectives: To minimize movement artifacts during tracer imaging studies, the animals are generally sedated. Although many reports describe the effect of barbiturates on brain function, less is published about the general impact on the extracerebral metabolism and tracer biodistribution. This report describes the influence of pentobarbital on tumor uptake of [{sup 123}I]-2-iodo-L-phenylalanine ([{sup 123}I]-2I-L-PA) using dissection and nuclear imaging. Methods: R1M tumor-bearing athymic mice were divided into two populations: untreated and pentobarbital-treated. Each group was subjected to dynamic and static planar imaging and organ dissection after [{sup 123}I]-2I-L-PA injection. Two-compartment blood modeling was performed. Analysis of variance (ANOVA), t test and clustered boxplot analyses were used to compare the results between the treatment groups and between the data acquisition methods. Results: Two-compartment blood modeling demonstrated that pentobarbital decreased the elimination velocity and the distribution toward the peripheral compartment. Both observations lead to higher blood pool and kidney activities after administering pentobarbital. The dependence of the differential absorption/differential uptake ratio results on the factors organ, method and treatment (3-factor ANOVA) demonstrated that all factors had a significant effect. Moreover, a significant effect for method and treatment was observed for each individual organ, and the ratio of tumor to background showed additionally an ordinal interaction between the latter two factors. Although the tumor uptake values were lower when using sedation and nuclear imaging, the tumor could still be visualized. Conclusions: An effect of sedation treatment and data acquisition method was demonstrated for 2-iodo-phenylalanine, currently under development as tumor tracer. It is recommended that animal experiments should include quantitative investigation of sedation and the data acquisition method.

  20. Residual brain viability, evaluated by (99m)Tc-ECD SPECT, in patients with suspected brain death and with confounding clinical factors. (United States)

    Bertagna, Francesco; Barozzi, Ottorino; Puta, Erinda; Lucchini, Silvia; Paghera, Barbara; Savelli, Giordano; Panarotto, Beatrice; Rodella, Carlo Alberto; Rebuffoni, Lina; Bosio, Giovanni; Terzi, Arturo; Giubbini, Raffaele


    In 1968, the Harvard criteria for brain death diagnosis were introduced in clinical practice. These include no movements or breathing, no reflexes, and flat electroencephalogram in the absence of confounding factors, including hypothermia, drugs, electrolyte, and endocrine disturbances. When confounding factors occur, confirmatory tests documenting the absence of cerebral blood flow, such as cerebral angiogram, transcranial Doppler sonography, computed tomography angiography, and nuclear techniques, are required. The aim of this study was to evaluate the clinical value of single-photon emission computed tomography (SPECT) with technetium-99m (Tc)-ECD in the diagnosis of brain death in a cohort of patients with confounding factors. Fifty-two patients were studied between 1 January 2000 and 23 September 2008. The criteria for the request for Tc-ECD SPECT were sodic thiopental withdrawal after less than 24 h, unreceptivity and unresponsivity of brainstem reflexes, anesthesia in the last 24 h, hypothermia, anamnesis for barbiturate use, electroencephalogram artefacts, toxic state, and pediatric criteria. All patients underwent Tc-ECD SPECT using a dual-headed camera fitted with a high-resolution low-energy collimator. Images were reconstructed and processed according to standard procedures and interpreted qualitatively by two experienced observers. The presence of spots of residual brain viability was observed in 13 patients: 25% of our patient cohort. The patients with residual viability were younger (aged 30.92+/-17.28 years) in comparison with those with no viability (41.91+/-18.77 years, P<0.031). Considering the eligibility for transplantation, there were 12 of 13 patients in the residual viability group and 31 of 39 in the no viability group (P<0.0001). All patients with spots of brain uptake were monitored daily by Tc-ECD SPECT, and all of them reached the condition of empty skull after one or multiple studies. The opposition to organ donation was observed in

  1. Uso abusivo de benzidamina no Brasil: uma abordagem em farmacovigilância Use abusive of benzydamine in Brazil: an overview in pharmacovigilance

    Directory of Open Access Journals (Sweden)

    Daniel Marques Mota


    Full Text Available O uso abusivo de medicamentos tem sido objeto de crescente interesse em saúde pública e geralmente veiculado na imprensa brasileira. Dentre os medicamentos, objeto de abuso e que causam dependência física e/ou psíquica, incluemse os barbitúricos, benzodiazepínicos, analgésicos opióides e anfetaminas. Os analgésicos, antitérmicos e antiinflamatórios não esteroidais, apesar de não fazerem parte dessa relação de fármacos, estão, geralmente, associados ao uso recreativo ou fins não terapêuticos. O objetivo deste ensaio é apresentar informações sobre o uso abusivo de benzidamina no Brasil. Trata-se de um estudo descritivo do tipo exploratório, em que foram utilizadas diferentes estratégias metodológicas adotadas na prática de regulação em farmacovigilância. O uso abusivo desse fármaco foi constatado na literatura científica, imprensa e internet. Em função da facilidade na compra de medicamentos sujeitos à prescrição médica, entre outros fatores, devem-se exigir meios e formas para monitorar a comercialização e utilização de medicamentos, assegurando seu uso seguro e racional, incluindo o fortalecimento da farmacovigilância no Brasil.The abusive drug use has been object of increasing concern in public health and is commonly issued in the Brazilian press. Amongst medicines, those that are abuse substances and cause physical and/or psychic dependence, barbiturates, benzodiazepines, opioid analgesics and amphetamines are included. Analgesics, antipyretics and non-steroidal anti-inflammatory drugs, even not making part of this list, are generally associated with recreational use or non therapeutical purpose. The objective of this essay is to present information on the abusive use of benzydamine in Brazil. The present study is an exploratory essay in which different methodological strategies adopted in the regulatory practice of pharmacovigilance have been used. The abusive use of this drug was evidenced in

  2. Patterns of Drugs and Drug Metabolites Observed in Meconium: What Do They Mean? (United States)

    McMillin, Gwendolyn A; Wood, Kelly E; Strathmann, Frederick G; Krasowski, Matthew D


    Meconium drug testing is performed to detect potentially harmful drug exposures in a newborn. Interpretation of meconium drug testing results can be complicated based on the patterns and proportional concentrations of the drug(s) and/or drug metabolite(s) detected. The objective of this study was to analyze meconium drug testing patterns in a de-identified dataset from a national reference laboratory (n = 76,631) and in a subset of the data, wherein specimens originated at a single academic medical center for which detailed chart review was possible (n = 3635). Meconium testing was performed using 11 immunoassay-based drug screens. Specimens that were positive for one or more drug screens were reflexed to corresponding confirmation tests performed by gas chromatography or liquid chromatography with mass spectrometric detection, targeted to identify and quantitate specific parent drug(s) and metabolite(s). The positivity rate was the highest for the cannabis metabolite 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (25.2%, n = 18,643), followed by opiates/oxycodone (23.2%, n = 17,778), amphetamine/methamphetamine (6.7%, n = 5134), cocaine metabolites (5.5%, n = 4205), methadone (5.3%, n = 4093), benzodiazepines (3.4%, n = 2603), barbiturates (1.1%, n = 834), propoxyphene (1.0%, n = 749), and phencyclidine (0.1%, n = 44). Based on documented pharmacy history, drugs administered to either the mother or newborn during the birth hospitalization were detected in meconium, providing evidence that drugs can be incorporated into meconium rapidly. Drugs administered directly to the newborn after birth were recovered in meconium as both parent drug and metabolites, providing evidence of neonatal metabolism. Overall, patterns observed in meconium exhibited many similarities to those patterns commonly reported with urine drug testing. Interpretation of meconium drug testing results requires comparison of results with clinical and analytical expectations, including maternal

  3. Synthesis and pharmacological evaluation of neurosteroid photoaffinity ligands

    Energy Technology Data Exchange (ETDEWEB)

    Savechenkov, Pavel Y.; Chiara, David C.; Desai, Rooma; Stern, Alexander T.; Zhou, Xiaojuan; Ziemba, Alexis M.; Szabo, Andrea L.; Zhang, Yinghui; Cohen, Jonathan B.; Forman, Stuart A.; Miller, Keith W.; Bruzik, Karol S.


    Neuroactive steroids are potent positive allosteric modulators of GABAA receptors (GABAAR), but the locations of their GABAAR binding sites remain poorly defined. To discover these sites, we synthesized two photoreactive analogs of alphaxalone, an anesthetic neurosteroid targeting GABAAR, 11β-(4-azido-2,3,5,6-tetrafluorobenzoyloxy)allopregnanolone, (F4N3Bzoxy-AP) and 11-aziallopregnanolone (11-AziAP). Both photoprobes acted with equal or higher potency than alphaxalone as general anesthetics and potentiators of GABAAR responses, left-shifting the GABA concentration – response curve for human α1β3γ2 GABAARs expressed in Xenopus oocytes, and enhancing [3H]muscimol binding to α1β3γ2 GABAARs expressed in HEK293 cells. With EC50 of 110 nM, 11-AziAP is one the most potent general anesthetics reported. [3H]F4N3Bzoxy-AP and [3H]11-AziAP, at anesthetic concentrations, photoincorporated into α- and β-subunits of purified α1β3γ2 GABAARs, but labeling at the subunit level was not inhibited by alphaxalone (30 μM). The enhancement of photolabeling by 3H-azietomidate and 3H-mTFD-MPAB in the presence of either of the two steroid photoprobes indicates the neurosteroid binding site is different from, but allosterically related to, the etomidate and barbiturate sites. Our observations are consistent with two hypotheses. First, F4N3Bzoxy-AP and 11-aziAP bind to a high affinity site in such a pose that the 11-photoactivatable moiety, that is rigidly attached to the steroid backbone, points away from the protein. Second, F4N3Bzoxy-AP, 11-aziAP and other steroid anesthetics, which are present at very high concentration at the lipid-protein interface due to their high lipophilicity, act via low affinity sites, as proposed by Akk et al. (Psychoneuroendocrinology 2009, 34S1, S59-S66).

  4. Oral and intravenous caffeine for treatment of children with post-sedation paradoxical hyperactivity. (United States)

    Rubin, Joan T; Towbin, Richard B; Bartko, MaryBeth; Baskin, Kevin M; Cahill, Anne Marie; Kaye, Robin D


    Paradoxical hyperactivity (PH) is a known complication of sedation in children, especially with barbiturates such as pentobarbital. The accompanying inconsolable irritability and agitation, similar to behaviors reported in children with attention deficit hyperactivity disorder (ADHD), is uncomfortable for the child and anxiety-provoking for parents and health-care workers. Our objective was to describe our experience with oral (PO) and intravenous (IV) caffeine as a treatment for sedation-induced PH. From January 2000 to April 2003, 19,894 children were sedated in our institution for radiology procedures. Of these, 360 children were diagnosed with PH. A total of 229 children exhibiting symptoms of PH after sedative administration were treated with PO caffeine ( n=88; 43 boys, 45 girls; mean age 4.5 years, mean weight 18.7 kg) or IV caffeine ( n=131; 73 boys, 58 girls; mean age 4.8 years, mean weight 20.1 kg) or both ( n=10; 8 boys, 2 girls; mean age 5.0 years, mean weight 19.9 kg). A positive effect was defined as a decrease in agitation, crying, or hyperactivity within 40 min of caffeine administration. A control group ( n=45) was obtained from those 141 children who experienced post-sedation PH but were not treated with caffeine, and matched for age and sex with samples of children treated with IV caffeine ( n=45) and PO caffeine ( n=45). Children treated intravenously received the equivalent of 20 mg/kg caffeine citrate (to a maximum of 200 mg). Of those treated with IV caffeine, 82/131 (63%) showed a positive effect, and returned to baseline behavioral status after an average of 33 min (SD=23 min). The untreated control group required a significantly longer time to recover ( Pcaffeine. Children treated orally received approximately 1.0-2.5 mg/kg caffeine in Mountain Dew (Pepsi-Cola Company), and 36/88 (41%) showed a positive effect and returned to baseline behavioral status after an average of 42 min (SD=27 min). Of the 10 children treated with both PO and IV

  5. Review of idiopathic eosinophilic meningitis in dogs and cats, with a detailed description of two recent cases in dogs : review and clinical communication

    Directory of Open Access Journals (Sweden)

    J.H. Williams


    Caesarian section after developing a non-responsive inertia 8 days prior to presentation. This animal's clinical signs included status epilepticus seizures unrelated to hypocalcaemia and warranted induction of a barbiturate coma. She died 4 hours later. Post mortem and histopathological findings in the brain were almost identical to those of the Boerboel and she also showed histological evidence of recent active intravascular haemolysis with microcyte formation. Rabies, distemper and Neospora caninum immunohistochemical stains were negative in the brains of both dogs. Immunohistochemical staining of the cerebral and meningeal exudates of the Beagle for T- and B-lymphocyte (CD3 and CD79a markers showed a predominance of T-lymphocytes with fewer scattered B lymphocytes. A possible allergic response to amoxicillin / clavulanate is considered, as this appeared to be the only feature common to the recent history of both animals. An overview of EME in humans, dogs and cats is given and the previously published cases of idiopathic EME in dogs and the single published cat case are briefly reviewed.


    Directory of Open Access Journals (Sweden)

    Zoran Bojanić


    for pharmacokinetic drug interactions. Although interactions with diazepam may be predictable in specific circumstances, when diazepam is used with: analgesics, anesthetics, anticonvulsants, antipsychotics, anxiolytics/sedatives, barbiturates, hypnotics, MAO inhibitors, narcotics, sedative anihistamines, phenothiazines and other antidepressants, careful consideration is needed.

  7. Manipulation of Intermolecular Interactions for Active Layer Morphology Optimization in Organic Photovoltaics (United States)

    Barreda, Leonel

    Organic photovoltaics (OPVs) are an attractive solar energy technology for low-current applications. Herein is described the supramolecular design and methodology to manipulate intermolecular interactions in order to create an active layer in OPVs devices composed of crystalline and amorphous donor-acceptor domains, which has been proposed as the ideal morphology for high performance. To this end, a series of symmetric and asymmetric diketopyrrolopyrrole (DPP) derivatives containing either an amide (capable of hydrogen-bonding) or ester endgroups were synthesized. The symmetric designs faced problems with solubility, strong segregation and low performance, so asymmetric donors having one amide/ester were used. Upon addressing initial stability problems, analysis of the ester films with X-ray diffraction displayed greater crystallinity and pi-pi stacking. The amide formed short aggregates with smaller, less ordered domains, resulting from competition between hydrogen bonding and pi-pi stacking, which interestingly endowed devices with higher current and 50% increase in device efficiency over the ester. To better match solar emission, the DPP core was substituted by benzodithiophene (BDT). Amides again outperformed esters, but introduction of a benzothiadiazole ?-spacer between the amide/ester endgroups led to electron traps and lowered performance; replacing it with phenyldithiophene reduced stacking ability. A recurring issue was the competition between noncovalent interactions, which motivated the use of barbituric acid endgroups, but solubility was compromised. After addressing each problem, a design having a BDT core with planar ?-spacers, connected by an alkyl linker to the hydrogen-bonding endgroups is predicted to display optimized optoelectronic properties and cooperative noncovalent interaction. Next, a series of BDT-core molecules with DPP endgroups and alkyl tails resembling solvent additives (which improve donor-acceptor interaction but increase

  8. Anesthesia and critical-care delivery in weightlessness: A challenge for research in parabolic flight analogue space surgery studies (United States)

    Ball, Chad G.; Keaney, Marilyn A.; Chun, Rosaleen; Groleau, Michelle; Tyssen, Michelle; Keyte, Jennifer; Broderick, Timothy J.; Kirkpatrick, Andrew W.


    BackgroundMultiple nations are actively pursuing manned exploration of space beyond low-earth orbit. The responsibility to improve surgical care for spaceflight is substantial. Although the use of parabolic flight as a terrestrial analogue to study surgery in weightlessness (0 g) is well described, minimal data is available to guide the appropriate delivery of anesthesia. After studying anesthetized pigs in a 0 g parabolic flight environment, our group developed a comprehensive protocol describing prolonged anesthesia in a parabolic flight analogue space surgery study (PFASSS). Novel challenges included a physically remote vivarium, prolonged (>10 h) anesthetic requirements, and the provision of veterinary operating room/intensive care unit (ICU) equivalency on-board an aircraft with physical dimensions of ethical approval, multiple ground laboratory sessions were conducted with combinations of anesthetic, pre-medication, and induction protocols on Yorkshire-cross specific pathogen-free (SPF) pigs. Several constant rate infusion (CRI) intravenous anesthetic combinations were tested. In each regimen, opioids were administered to ensure analgesia. Ventilation was supported mechanically with blended gradients of oxygen. The best performing terrestrial 1 g regime was flight tested in parabolic flight for its effectiveness in sustaining optimal and prolonged anesthesia, analgesia, and maintaining hemodynamic stability. Each flight day, a fully anesthetized, ventilated, and surgically instrumented pig was transported to the Flight Research Laboratory (FRL) in a temperature-controlled animal ambulance. A modular on-board surgical/ICU suite with appropriate anesthesia/ICU and surgical support capabilities was employed. ResultsThe mean duration of anesthesia (per flight day) was 10.28 h over four consecutive days. A barbiturate and ketamine-based CRI anesthetic regimen supplemented with narcotic analgesia by bolus administration offered the greatest prolonged hemodynamic

  9. Risk of respiratory depression with opioids and concomitant gabapentinoids

    Directory of Open Access Journals (Sweden)

    Savelloni J


    Full Text Available Julie Savelloni,1 Heather Gunter,2 Kelly C Lee,3 Chih Hsu,1 Cassia Yi,2 Kyle P Edmonds,4 Timothy Furnish,5 Rabia S Atayee1 1Department of Pharmacy, UC San Diego Health, San Diego, CA, USA; 2Department of Nursing, UC San Diego Health, San Diego, CA, USA; 3Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA; 4Department of Medicine, UC San Diego Health Sciences, San Diego, CA, USA; 5Department of Anesthesiology, UC San Diego Health, San Diego, CA, USA Introduction: The combination of opioids and central nervous system depressants such as benzodiazepines and barbiturates has an additive effect on the frequency of oversedation and respiratory depression requiring naloxone use in hospitalized patients. Gabapentinoids (gabapentin and pregabalin are frequently prescribed with opioids for their opioid-sparing and adjuvant analgesic effects. There is limited literature on the risk of respiratory depression due to the combination of opioids and gabapentinoids requiring naloxone administration. Methods: This retrospective study evaluated patients who were prescribed opioids and at least one dose of naloxone between March 1, 2014 and September 30, 2016. The primary objective of this study was to compare the frequency of respiratory depression among patients who received naloxone and opioids (non-gabapentinoid group with those who received naloxone, opioids, and gabapentinoids (gabapentinoid group. Secondary objectives included comparing the association of oversedation, using the Pasero Opioid-induced Sedation Scale, and various risk factors with those in the gabapentinoid group. Results: A total of 153 patient episodes of naloxone administration (102 in the non-gabapentinoid and 51 in the gabapentinoid groups in 125 unique patients were included in the study. For the primary objective, there were 33 episodes of respiratory depression associated with the non-gabapentinoid group (33/102=32.4% versus 17

  10. [The protection of heme oxygenase-1 from acute cardiocyte injury in rats]. (United States)

    Yang, Ren-qiang; Cheng, Xiao-shu; Liu, Chen; Wang, Ling; Li, Ping; Wu, Yan-qing; Wu, Qing-hua; Su, Hai; Dai, Yu-cheng


    To observe the protection of Heme oxygenase-1 (HO-1) from lipopolysaccharide (LPS)-induced cardiocyte injury and its mechanism. Cardiocyte was isolated from SD neonate rat and cultured in vitro, and was divided into control group (normal culture), LPS group (with stimulation of 30 micromoL/L LPS for 1 hour), LPS + Hemin group (with same treatment to LPS group after stimulation of 5 micromoL/L Hemin for 1 hour), and LPS + ZnPP group (with same treatment to LPS group after stimulation of 3 micromoL/L ZnPP for 1 hour). The level of lactic-dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) were measured by thio-barbituric acid and xanthine oxidase techniques. The cell heart rhythm, survival rate and apoptosis rate were examined. The expressions of nuclear factor kappaB (NF-kappaB), HO-1 and tumor necrosis factor-alpha (TNF-alpha) were measured with Western blotting. The HO-1 mRNA was examined by RT-PCR. The level of LDH and MDA in LPS, LPS + Hemin, and LPS + ZnPP groups were (113 +/- 15), (79 +/- 13), (154 +/- 22) U/L, and (1.88 +/- 0.36), (1.16 +/- 0.32), (2.84 +/- 0.44) mmoL/L respectively, which were all obviously higher than those in control group [(69 +/- 10) U/L, (0.87 +/- 0.25) mmol/L, P ZnPP groups (17.8 +/- 1.8, 22.5 +/- 2.4, 13.4 +/- 1.5 U/mL, respectively) was all obviously lower than that in control group (24.3 +/- 3.6 U/mL, P ZnPP groups than those in control group (P ZnPP groups was higher than that in control group (P ZnPP groups was higher than those in control group (P ZnPP group was highest. LPS can induce cardiocyte injury, which can be inhibited through the anti-inflammatory, anti-oxidant, and anti-apoptosis functions by HO-1.

  11. [The history of sleep research in the 20th century]. (United States)

    Mathis, J


    certainly the sleep-apnea syndrome. Charles Dickens described in his 'Pickwick Papers' subjects with this illness already 150 years ago. The pathogenetic significance of the apneas during sleep, however, were recognized in 1965 only by Gastaut and at the same time by Jung and Kuhlo. Treatment for insomniacs was restricted for many years to alcohol, opium and barbiturates. Following the horrible sequelae of thalidomide therapy in 1956, a more efficient treatment was available through the introduction of benzodiazepines after 1960.

  12. Tratamento da epilepsia na infância com mogadon Treatment of epilepsy in children with Mogadon

    Directory of Open Access Journals (Sweden)

    Antonio B. Lefèvre


    Full Text Available São analisados os resultados obtidos com o emprego do Mogadon em 68 casos de epilepsia em crianças (34 com síndrome de West, 14 com epilepsia tipo P.M. ausência simples e 20 com formas atípicas de P.M., todos rebeldes aos tratamentos convencionais experimentados em várias combinações, e durante tempo variável, porém quase sempre bastante longo. A maioria dos pacientes apresentava intenso retardamento psicomotor, provavelmente decorrente da longa evolução não controlada da epilepsia. Os resultados foram muito bons no que diz respeito ao controle das crises (100% em 28, 75% em 22, 50% em 10, 25% em um e nulo apenas em 7 casos. O resultado sôbre o desenvolvimento psicomotor foi menos brilhante, pois poucos pacientes melhoraram com o controle das crises. Os efeitos colaterais foram pouco importantes, tendo sido nulos em 41; em 23 foi notada sonolëncia (em dois acompanhada de ataxia; em 4 houve queixa de insônia controlável com barbitúricos. O seguimento após o tratamento variou de 6 a 18 meses.Therapeutic results with Mogadon in 68 children with epilepsy (34 cases of West syndrome, 14 with tipical P.M. seizures, 20 with atypical P.M. seizures resistant to conventional therapy employed previously in various combinations for prolonged periods, is reported. The majority of the patients showed intense psychomotor retardation, probably due to the non-controlled evolution of the cases, before the administration of Mogadon. Results were excellent in regard to the control of the crise's frequency (100% in 28, 75% in 22, 50% in 10, 25% in one, and null in 7 cases. Concerning the psychomotor development the results were less evident. Side effects were negligible, being absent in 41 cases; 23 patients showed somnolence, accompanied by ataxia in two cases. Four patients complained of insomnia, promptly controlled with barbiturates. The period of post-treatment follow-up ranged between 6 and 18 months.

  13. Xilazina como pré-medicação para anestesia com tiopental sódico em cães Xylazine as a pre-medicant for thiopental sodium anaesthesia in the dog

    Directory of Open Access Journals (Sweden)

    Orlando Ribeiro Prado Filho


    Full Text Available A xilazina produz um bom efeito sedativo-analgésico quando associado à drogas anestésicas. O tiopental sódico é um barbitúrico de curta duração que produz sonolência, sedação e hipnose. O objetivo deste trabalho é verificar a eficiência da associação da xilazina como pré-medicação e do tiopental sódico na manutenção da anestesia, em cães. Foram usados 32 cães sem raça definida, adultos, machos e com peso entre 8 e 10 kg, que foram submetidos à procedimento operatório no esôfago cervical. A dose média de xilazina administrada foi de 3,8 mg/kg e de tiopental sódico foi de 7,7 mg/kg. Não houve necessidade de intubação endotraqueal e não ocorreu óbito relacionado com as medicações anestésicas. Concluindo, o procedimento anestésico descrito é de fácil execução, é seguro e diminui o estresse do animal.The xylazine produce reliable sedative-analgesic effect when coadministered with anesthetics drugs. Thiopental sodium is a shorter duration barbituric, produced somnolence, sedation and hypnosis. The aim of this work is to verify the efficiency in association of xylazine and thiopental sodium to anesthesia in dogs. Thirty-two male mongrel dogs with an average weight between 8 and 10 kg were submitted to surgical procedure with approach of cervical aesophagus. The average dose was 3,8 mg/kg to xilazine and 7,7 mg/kg to thiopental sodium. Was not necessary endotracheal intubation and no deaths due anesthesic procedure were observed. The anesthesic procedure described is easy, safe and decreases the stress of the animal.

  14. Kilpauk Mental Hospital: The Bethlem of South Asia - A recall of its history prior to 1970. (United States)

    Somasundaram, O; Ratnaraj, Ponnudurai


    The magnificent "Institute of Mental Health" has its history almost from 1795 when the East India company appointed Surgeon Valentine Conolly to be in charge of a "House for accommodating persons of unsound mind." After a few transitions, backed by a government order for the construction of a lunatic asylum in a 66 1/2 acre site, the asylum started functioning from 1871. The period of about six decades from its inception could be referred to as "the period of custodial care." However, the quality of care for the general medical problems gradually improved with the creation of separate facilities for some common ailments and also one for seriously ill. Separate wards were also conceptualized for criminal patients and female inmates. Thanks to Government sanctions, the staff strength gradually increased with regularization of bed strength to 1800, and by 1948-1957, the hospital had 14 medical officers and a host of other staff. The period from 1939 to 1948 witnessed the introduction of electroconvulsive therapy and insulin coma therapy including the modified one and also insulin histamine therapy. During the prephenothiazine era, the drugs used were barbiturates, paraldehyde, opiates, and Rauwolfia serpentina, which were discontinued after the use of Chlorpromazine from 1954. Psychosurgery was also undertaken in selected cases from 1948, but the procedure went out of vogue soon due to the quality of outcome being poor and development of complications. Rehabilitation of patients got a fillip with the introduction of occupation therapy in 1949 and industrial therapy center in 1970. Extension of psychiatric services to general hospitals began from 1949. Regular training was imparted to paramedical and undergraduate medical students from 1948. The institute had the privilege of hosting the Annual National Conference of Indian Psychiatric Society - 1957. The institute also spearheaded in several pioneering researches such as insulin coma therapy, syphilis, and Alzheimer

  15. Kratom alkaloids and O-desmethyltramadol in urine of a "Krypton" herbal mixture consumer. (United States)

    Arndt, Torsten; Claussen, Ulrich; Güssregen, Brunhilde; Schröfel, Stefanie; Stürzer, Birgit; Werle, Annika; Wolf, Gerald


    A drug and alcohol withdrawal rehabilitation centre requested an analysis for "Krypton" in urine of a former opiate-addictive woman. She showed an altered clinical picture and behaviour with miosis, itchiness, agitation, and moderate euphoria after 3 months of until than successful treatment. Literature search revealed that "Krypton" is said to contain "Kratom" (leaves of Mitragyna speciosa), but could also contain O-desmethyltramadol (European Monitoring Centre for Drugs and Drug Addiction thematic paper "Spice"). Immunological drug screenings were done with test strips (nal von minden, Regensburg, Germany) and with cloned enzyme donor immunoassay (Microgenics, Passau, Germany). "Kratom" alkaloids and tramadol (metabolites) were analyzed by LC-MS/MS (ThermoFisher Scientific Quantum Ultra Triple Quadrupole mass spectrometer). Immunoassays were negative for amphetamines, barbiturates, benzodiazepines, benzoylecgonine, buprenorphine, ethylglucuronide, methadone (metabolite), opiates, oxycodone, and THC-COOH, and test strips were negative for tramadol and its metabolites (cut-off 10 mg/L for O-desmethyltramadol). LC-MS/MS detected the "Kratom" alkaloids mitragynine, speciociliatine, speciogynine, mitraciliatine, and paynantheine and approximately 9mg/L O-desmethyltramadol, but no tramadol and N-desmethyltramadol. The detection of M. speciosa alkaloids is a proof of "Kratom" abuse. Confronted with the analysis data, the patient admitted to have consumed 3-4 infusions of "Krypton". The origin of the O-desmethyltramadol is unclear. Tramadol abuse is unlikely since tramadol and N-desmethyltramadol (physiologically occurring in urine after tramadol intake) were not detectable. Consumption of a "Krypton" product spiked with O-desmethyltramadol could explain our findings and the patient's clinical picture. This would be in agreement with a most recent report about spiking apparently natural herbal mixtures with the synthetic opioid O-desmethyltramadol. Analysis of "Kratom

  16. Hair analysis to monitor abuse of analgesic combinations containing butalbital and propyphenazone. (United States)

    Ferrari, Anna; Tiraferri, Ilaria; Palazzoli, Federica; Verri, Patrizia; Vandelli, Daniele; Marchesi, Filippo; Ciccarese, Michela; Licata, Manuela


    Butalbital, a barbiturate, is present in analgesic combinations used by headache sufferers. Overuse/abuse of these combinations may cause dependence, chronic migraine, and medication-overuse headache (MOH). MOH is difficult to manage: it improves interrupting analgesic overuse, but requires monitoring, because relapses are frequent. A gas chromatography-mass spectrometry (GC-MS) method for hair analysis has been developed and validated to document abuse of an analgesic combination containing butalbital and propyphenazone by a patient with MOH. For over ten years the patient managed her headache using eight suppositories/day of an analgesic combination containing butalbital 150mg, caffeine 75mg, and propyphenazone 375mg per suppository. An outpatient detoxification treatment was carried out. After three weeks, the patient reduced the consumption to one suppository/day. At the first control visit, after three months from the beginning of detoxification, the patient increased the use of the combination to four suppositories/day and at the second control visit, after seven months from the beginning of detoxification, she was back to eight suppositories/day. At the two control visits, a hair sample was taken for determination of butalbital and propyphenazone. Moreover blood and urine samples for determination of butalbital were drawn at the beginning of detoxification treatment and at the two control visits. With the segmental analysis of two hair samples the medication history of ten months could be estimated. In the first hair sample, collected at the first control visit, in the distal segment, butalbital and propyphenazone concentrations were, respectively, 17.5ng/mg and 56.0ng/mg, confirming the prolonged abuse; in the proximal segment, concurrently with the detoxification treatment, butalbital and propyphenazone concentrations had reduced respectively to 5.45ng/mg and 11.1ng/mg. The second hair sample, collected at the second control visit, proved the fair course

  17. Synthesis and pharmacological evaluation in mice of halogenated cannabidiol derivatives. (United States)

    Usami, N; Okuda, T; Yoshida, H; Kimura, T; Watanabe, K; Yoshimura, H; Yamamoto, I


    Six halogenated derivatives of cannabidiol (CBD, 1) substituted on the aromatic ring at the 3' and/or 5' position, 3'-chloro- (2), 3',5'-dichloro- (3), 3'-bromo- (4), 3',5'-dibromo- (5), 3'-iodo- (6) and 3',5'-diiodo-CBD (7) were synthesized and their pharmacological effects of barbiturate-induced sleep prolongation, anticonvulsant effects and locomotor activity were evaluated by intravenous (i.v.) injection in mice. 2 (10 mg/kg, i.v., 69 +/- 10 min) significantly prolonged pentobarbital-induced sleeping time by 3.1-fold, compared to control (22 +/- 2 min), although other 1 derivatives used did not significantly affect the sleeping time. 2, 4 and 6 (10 mg/kg, i.v.) significantly prolonged hexobarbital-induced sleeping time by 2.0-, 2.0- and 2.3-fold, respectively, compared with control (52 +/- 5 min). On the other hand, 1 and all halogenated derivatives did not significantly prolong barbital-induced sleeping time. The monohalogenated derivatives, 2, 4 and 6 were able to prolong pentobarbital and hexobarbital-induced sleeping time, although the dihalogenated derivatives, 3, 5 and 7 did not exhibit a prolongation of the sleeping time. All halogenated derivatives of 1 except for brominated derivatives (2, 3, 6, 7) tended to prolong tonic seizure latency induced by pentylenetetrazol. 1 and its halogenated derivatives did not exhibit any prolongation of seizure latency induced by picrotoxin or strychnine. Maximal electroshock test demonstrated that 1 and 4 exhibited almost the same potency in their anticonvulsant effects, although other 1 derivatives 2, 3, 5, 6 and 7 did not show significant effect up to a dose of 63 mg/kg, i.v. The ED50 values (mg/kg, i.v.) of 1 and 4 were 38 and 44, respectively. 1 and 4 also showed anticonvulsant effect in minimal and maximal electroshock-threshold tests. 2, 4 and 6 tended to decrease the total distance (horizontal activity) and number of rearings (vertical activity) of mice, whereas 3, 5 and 7 tended to increase the number of

  18. Management of cancer pain: 1. Wider implications of orthodox analgesics

    Directory of Open Access Journals (Sweden)

    Lee SK


    Full Text Available Susannah K Lee,1 Jill Dawson,2 Jack A Lee,3 Gizem Osman,4 Maria O Levitin,5 Refika Mine Guzel,5 Mustafa BA Djamgoz5,61Pomona College, Claremont, CA, USA; 2Healthcare Communications Consultancy, Danville, CA, USA; 3College of Arts and Sciences, Vanderbilt University, Nashville, TN, USA; 4Department of Chemical Engineering, Loughborough University, Loughborough, UK; 5Division of Cell and Molecular Biology, Neuroscience Solutions to Cancer Research Group, South Kensington Campus, Imperial College London, London, UK; 6Cyprus International University, Biotechnology Research Centre, Haspolat, North Cyprus, Mersin, TurkeyAbstract: In this review, the first of two parts, we first provide an overview of the orthodox analgesics used commonly against cancer pain. Then, we examine in more detail the emerging evidence for the potential impact of analgesic use on cancer risk and disease progression. Increasing findings suggest that long-term use of nonsteroidal anti-inflammatory drugs, particularly aspirin, may reduce cancer occurrence. However, acetaminophen may raise the risk of some hematological malignancies. Drugs acting upon receptors of gamma-aminobutyric acid (GABA and GABA “mimetics” (eg, gabapentin appear generally safe for cancer patients, but there is some evidence of potential carcinogenicity. Some barbiturates appear to slightly raise cancer risks and can affect cancer cell behavior in vitro. For cannabis, studies suggest an increased risk of squamous cell carcinoma of the tongue, larynx, and possibly lung. Morphine may stimulate human microvascular endothelial cell proliferation and angiogenesis; it is not clear whether this might cause harm or produce benefit. The opioid, fentanyl, may promote growth in some tumor cell lines. Opium itself is an emerging risk factor for gastric adenocarcinoma and possibly cancers of the esophagus, bladder, larynx, and lung. It is concluded that analgesics currently prescribed for cancer pain can

  19. Antioxidant and antimicrobial effects of condiments paste used as nitrite replacer in chicken mince

    Directory of Open Access Journals (Sweden)

    Meena Goswami


    Full Text Available Aim: The present study was conducted to evaluate the antioxidant and antimicrobial effects of 4% Ginger + 4% Garlic + Turmeric 1000ppm (GGT, nitrite 200ppm (N and the control (C on minced chicken stored at 4±10C. Materials and Methods: Physico-chemical properties (pH, Thio Barbituric acid value (TBA, Peroxide value (PV and Free Fatty acid (FFA were evaluated on 0, 3, 6 and 9th day of the storage. The antimicrobial studies viz. Total viable count (TVC, Escherichia coli count, Clostridium sporogenes count and Clostridium perfringens count were carried out on 1, 4, 7 and 10th day of storage. Results: Highly significant difference (P<0.01 was noticed between the treatments and between the storage periods in pH (5.951±0.02-GGT as compared to C-5.898±0.05and N-5.899±0.02, TBA(0.566±0.09-GGT as compared to C-1.569±0.04m and N-0.614±0.11, PV(1.679±0.18-GGT as compared to C-2.595±0.41and N-2.03±0.21, FFA(1.199±0.21-GGT as compared to C-2.284±0.40 and N-1.446±0.24 and N-7.194±0.68, TVC (log CFU/g (7.528±0.70-GGT as compared to C-8.583±0.49 and N-6.446±0.53, Escherichia coli (log CFU/g (6.476±0.54-GGT as compared to C-7.658±0.71 and N-6.609±0.61, Clostridium sporogenes count (log CFU/g (7.746±0.69-GGT as compared to C-8.681±0.74 and N- and Clostridium perfringens count (log CFU/g (6.864±0.76-GGT as compared to C-8.790±0.53 and N-6.864±0.58. Conclusion: The Ginger garlic turmeric paste has an excellent potential to replace the nitrite as a natural antioxidant with other advantages. It is highly effective against Escherichia coli. It is also significantly effective against Clostridium perfringens, Clostridium sporogenes and TVC as compared to C but lesser than N. We recommend further research by replacing the nitrite with various combinations of the spices and the condiments.

  20. Protective Effect ofPluchea lanceolataagainst Aluminum Chloride-induced Neurotoxicity in Swiss Albino Mice. (United States)

    Mundugaru, Ravi; Sivanesan, Senthilkumar; Udaykumar, Padmaja; Rao, Niranjan; Chandra, Naveen


    potentials for treating diseases associated with neuronal toxicity. Abbreviations used: HAPL: Hydro alcoholic extract of Pluchea lanceolata ; CAT: Catalase; GSH-Px: Glutathione peroxidase; SOD: Superoxide dismutase; TBARS: Thio-barbituric acid reactive substances; MDA: Malondialdehyde; AChE: Acetylcholine esterase; AOT: Acute oral toxicity; CNS: Central nervous system; H 2 O 2 : Hydrogen peroxide; ML: molecular layer; GL: granular layer; MC: microcytic changes; BV: blood vessels; DG: dentate gyrus; PC: pyramidal cells; LD: Lethal dose; ANOVA: Analysis of variance; SEM: Standard error of mean; PCL: Pyramidal cell layer; OCL: Outer granular layer; BV: blood vessels; PM: Pia mater.

  1. La anestesiología, profesión signada por la drogadicción Anesthesiology and drug addiction

    Directory of Open Access Journals (Sweden)

    Tiberio Alvarez Echeverri


    Full Text Available

    Se informa sobre la prevalencia de drogadicción y alcoholismo entre los anestesiólogos, cuyas cifras alcanzan el 2% del total. Las drogas más utilizadas son: fentanil y otros opioides, diazepam, alcohol, anestésicos inhalados, ketamina, barbitúricos, sulfentanil, cocaína, morfina y heroína. Entre los factores de riesgo figuran algunos comunes a la población adicta en general (predisposición genética, exposición ambiental, falta de educación, de programas preventivos y de estrategias de control, estrés y otros peculiares a estos profesionales: disponibilidad de las drogas, autoprescripción, actitud permisiva de los colegas. El tratamiento tiene como objetivos desintoxicar a la persona y lograr que viva sin usar fármacos, que recupere sus aspectos social y ocupacional, que mantenga el tratamiento interdisciplinario, se vincule a grupos de soporte y psicoterapia y se reintegre plenamente a las actividades de la vida diaria una vez haya signos de franca recuperación. Incluye, además, identificar los problemas psiquiátricos de fondo, establecer metas de recuperación a largo plazo y utilizar, si es necesario, drogas antagonistas.

    Prevalence of drug addiction and alcoholism among anesthesiologists has been reported to be around 2%. Most frequently utilized drugs are phentanyl and other opioids, diazepam, alcohol, inhaled anesthetics, ketamine, barbiturates, sulphentanyl, cocaine, morphine and heroine. Besides risk factors that are common to the whole population (genetic predisposition, environmental exposure, stress and lack of education, preventive programs and control strategies, there are others peculiar to anes. thesiologists: availability of drugs, self. prescription and permissivenes of colleagues. Objectives of treatment are: to achieve detoxification and a drug-free life, to recuperate the social and occupational aspects of life, to adhere to

  2. Using molecular similarity to highlight the challenges of routine immunoassay-based drug of abuse/toxicology screening in emergency medicine

    Directory of Open Access Journals (Sweden)

    Siam Mohamed G


    Full Text Available Abstract Background Laboratory tests for routine drug of abuse and toxicology (DOA/Tox screening, often used in emergency medicine, generally utilize antibody-based tests (immunoassays to detect classes of drugs such as amphetamines, barbiturates, benzodiazepines, opiates, and tricyclic antidepressants, or individual drugs such as cocaine, methadone, and phencyclidine. A key factor in assay sensitivity and specificity is the drugs or drug metabolites that were used as antigenic targets to generate the assay antibodies. All DOA/Tox screening immunoassays can be limited by false positives caused by cross-reactivity from structurally related compounds. For immunoassays targeted at a particular class of drugs, there can also be false negatives if there is failure to detect some drugs or their metabolites within that class. Methods Molecular similarity analysis, a computational method commonly used in drug discovery, was used to calculate structural similarity of a wide range of clinically relevant compounds (prescription and over-the-counter medications, illicit drugs, and clinically significant metabolites to the target ('antigenic' molecules of DOA/Tox screening tests. These results were compared with cross-reactivity data in the package inserts of immunoassays marketed for clinical testing. The causes for false positives for phencyclidine and tricyclic antidepressant screening immunoassays were investigated at the authors' medical center using gas chromatography/mass spectrometry as a confirmatory method. Results The results illustrate three major challenges for routine DOA/Tox screening immunoassays used in emergency medicine. First, for some classes of drugs, the structural diversity of common drugs within each class has been increasing, thereby making it difficult for a single assay to detect all compounds without compromising specificity. Second, for some screening assays, common 'out-of-class' drugs may be structurally similar to the target

  3. Talidomida: indicações em Dermatologia Thalidomide: indications in Dermatology

    Directory of Open Access Journals (Sweden)

    Rubem David Azulay


    mucous, pruritus, cutaneous eruption, weight gain, hypothyroidism, neutropenia, bradycardia or tachycardia, and hypotension. It interacts with other medicine: barbiturates, chlorpromazine, reserpine, alcohol, acetaminophen, histamine, serotonin and prostaglandin.

  4. Bizarre behavior during intracarotid sodium amytal testing (Wada test: are they predictable? Reações bizarras durante o teste do amital sódico intracarotídeo (TASI ou Teste de Wada: é possível prevê-las?

    Directory of Open Access Journals (Sweden)

    Luciano de Paola


    Full Text Available The intracarotid sodium amytal test (ISAT or Wada Test is a commonly performed procedure in the evaluation of patients with clinically refractory epilepsy candidates to epilepsy surgery. Its goal is to promote selective and temporary interruption of hemispheric functioning, seeking to define language lateralization and risk for memory compromise following surgery. Behavioral modification is expected during the procedure. Even though it may last several minutes, in most cases it is subtle and easily manageable. We report a series of patients in whom those reactions were unusually bizarre, including agitation and aggression. Apart of the obvious technical difficulties (patients required physical restraining those behaviors potentially promote testing delay or abortion and more importantly, inaccurate data. We reviewed those cases, seeking for features that might have predicted their occurrence. Overall, reactions are rare, seen in less than 5% of the ISAT procedures. The barbiturate effect, patients' psychiatric profiles, hemisphere dominance or selectiveness of the injection were not validated as predictors. Thorough explanation, repetition and simulation may be of help in lessening the risk of those reactions.O teste do amital sódico intracarotídeo (TASI ou teste de Wada é procedimento comum na avaliação de pacientes portadores de epilepsia clinicamente refratária candidatos a cirurgia de epilepsia. Tem por objetivo promover interrupção seletiva e temporária da função hemisferial, definindo lateralização de linguagem e risco de comprometimento de memória no pós-operatório. São esperadas mudanças comportamentais durante o teste, as quais podem durar vários minutos, porém, em geral, são sutis e facilmente manejáveis. Relatamos uma série de casos em que ocorreram comportamentos pouco usuais, bizarros, incluindo agitação e agressividade. Estes comportamentos comprometem o teste (paciente deve ser contido, podendo levar a

  5. Relating the shape of protein binding sites to binding affinity profiles: is there an association?

    Directory of Open Access Journals (Sweden)

    Bitter István


    , except for few specific cases, the shapes of the binding pockets have relatively low weights in the determination of the affinity profiles of proteins. Since the MAF profile is closely related to the target specificity of ligand binding sites we can conclude that the shape of the binding site is not a pivotal factor in selecting drug targets. Nonetheless, based on strong specific associations between certain MAF profiles and specific geometric descriptors we identified, the shapes of the binding sites do have a crucial role in virtual drug design for certain drug categories, including morphine derivatives, benzodiazepines, barbiturates and antihistamines.

  6. Use of analgesic, anesthetic, and sedative medications during pediatric hospitalizations in the United States 2008. (United States)

    Lasky, Tamar; Ernst, Frank R; Greenspan, Jay


    The wide need for analgesia, anesthesia, and sedation in children and the lack of pediatric labeling leads to widespread off-label use of medications for pain and sedation in children. Any attempt to address the lack of labeling will require national estimates of the numbers of children using each medication, their ages, and other factors, to understand the overall use of these medications. We describe use of analgesics, anesthetics, and sedatives in pediatric inpatients by result of conducting a statistical analysis of medication data from >800,000 pediatric hospitalizations in the United States. The purpose was to provide national estimates for the percentage of hospitalized children receiving specific analgesics, anesthetics, and sedatives and their use by age group. Data from the Premier Database, the largest hospital-based, service-level comparative database in the country, were used. We identified all uses of a given medication, selected the first use for each child, and calculated the prevalence of use of specific medications among hospitalized children in 2008 as the number of hospitalizations in which the drug was used per 100 hospitalizations. Dose and number of doses were not considered in these analyses. The dataset contained records for 877,201 hospitalizations of children younger than 18 years of age at the time of admission. Thirty-three medications and an additional 11 combinations were administered in this population, including nonsteroidal antiinflammatory drugs, local and regional anesthetics, opioids, benzodiazepines, sedative-hypnotics, barbiturates, and others. The 10 most frequently administered analgesic, anesthetic, or sedative medications used in this population were acetaminophen (14.7%), lidocaine (11.0%), fentanyl (6.6%), ibuprofen (6.3%), morphine (6.2%), midazolam (4.5%), propofol (4.1%), lidocaine/prilocaine (2.5%), hydrocodone/acetaminophen (2.1%), and acetaminophen/codeine (2.0%). Use changed with age, and the direction of change

  7. Quantification of sodium pentobarbital residues from equine mortality compost piles. (United States)

    Payne, J; Farris, R; Parker, G; Bonhotal, J; Schwarz, M


    findings confirm the persistence of sodium pentobarbital from equine mortality compost piles and emphasize the importance of proper carcass management of animals euthanized with a barbiturate to reduce environmental impact and secondary toxicosis.

  8. Influence of Pentobarbital-Na on Stimulation-Evoked Catecholamine Secretion in The Perfused Rat Adrenal Gland (United States)

    Lim, Dong-Yoon; Kang, Tae-Joon; Hong, Soon-Pyo; Chung, Choon-Hae; Choi, Cheol-Hee; Lee, Seung-II; Park, Yoo-Whan; Kwack, Jae-Jung; Ki, Jang-Do; Kim, Chang-Wook; Park, Chi-Young


    Objectives The present study was attempted to investigate the effects of pentobarbital-Na, one of the barbiturates which are known to depress excitatory synaptic transmission in the central nervous system at concentrations similar to those required for the induction and maintenance of anesthesia, on catecholamines (CA) secretion evoked by cholinergic stimulation and membrane-depolarization from the isolated perfused rat adrenal gland, and to clarify the mechanism of its action. Methods Mature male Sprague-Dawley rats were anesthetized with thiopenal-Na(40mg/kg, s.c.). The adrenal gland was isolated by the methods of Wakade. A cannula used for perfusion of the adrenal gland was inserted into the distal end of the renal vein. The adrenal gland was carefully removed from the animal and placed on a platform of a leucite chamber. Results The perfusion of pentobarbital-Na(30–300uM) into an adrenal vein for 20 min produced relatively dose-dependent inhibition in CA secretion evoked by ACh(5.32mM) DMPP(100uM for 1 min), McN-A-343(200uM for 2 min), Bay-K-8644(10uM) and high potassium(56mM), while it did not affect the CA secretion of cyclopiazonic acid(10uM). Also, in the presence of thiopental-Na (100uM), CA secretory responses evoked by ACh, DMPP, McN-A-343 and high K+ were markedly depressed. Moreover, in adrenal glands preloaded with ketamine(100uM for 20 min), which is known to be a dissociative anesthetic, CA secretion evoked by ACh, DMPP, McN-A-343 and high K+ were significantly attenuated. Conclusion Taken together, these experimental results suggest that pentobarbital-Na depresses CA release evoked by both cholinergic stimulation and membrane-depolarization from the isolated rat adrenal medulla and that this inhibitory activity may be due to the result of the direct inhibiton of Ca++ influx into the chromaffin cells without any effect on the calcium mobilization from the intracellular store. PMID:9439151

  9. Atividade elétrica cerebral do rato com lesões da formação reticular mesencefálica Electrocorticographic study of the rats's bram after lesioning of the midbrain reticular formation

    Directory of Open Access Journals (Sweden)

    Walter C. Pereira


    , denotando fases de maior ou menor sincronização do traçado; c ondas teta nas áreas límbicas (talvez evidenciando alerta registradas simultâneamente com fusos em áreas neocorticais.Seventy three rats were prepared for acute and chronic experiments. The midbrain reticular formation was electrolitically destroyed (3,5 — 4,0 mA and 5 — 10 sec by means of an active electrode estereotactically guided according with the atlas of König an Klippel. The procedure was destined to provoke parcial, total, unilateral and bilateral lesions in different preparations. The ECoG was recorded with a 4-channel Beckman polygraph. Short bipolar leads were used in all experiments. 1. Spindling wich occurred after the operation was similar to spindling found in phisiological sleep and in barbiturate narcosis as well. Similarity was striking as to the electrophysiological properties and cortical projections. However, the duration of the individual potentials dispersed much more than in the above mentioned conditions (20 — 80 msec, wich may be related to the higlher complexity exhibited by the spindles which appear on the ECoG after destruction of the reticular formation of the midbrain, possibly due to lack of reticular timing of the thalamic synchronizing system activity, since spindling was more regular when circumscribed lesions of the midbrain were made. 2. The mechanisms involved in production of spindles during spontaneous and barbiturate sleep and after lesioning of the midbrain reticular formation are at least partially dependent upon reticular blocking. 3. The midbrain reticular formation activates mainly the ipsilateral hemisphere. The crossed component of the activating system is, probably, brought in action only when arousing stimuli are very strong. 4. Besides midbrain reticular formation other cortical activating mechanisms certainly play a role in arousing, since, in acute preparations, simultaneously with neocortical spindling, we frequently recorded: a short

  10. Consumo de drogas y violencia laboral en mujeres trabajadoras de Monterrey, N. L., México Consumo de drogas e violência ocupacional em mulheres trabalhadoras de Monterrey, N. L. México Drug consumption and occupational violence in working women of Monterrey, N. L., Mexico

    Directory of Open Access Journals (Sweden)

    Maria Magdalena Alonso Castillo


    qualitative approach. Results indicated that 37.1% of women consumed alcohol, 29.1% tobacco, 0.4% marihuana, 0.1% inhalants, and, among medical drugs, 5% consumed tranquilizers, and 1% other substances (barbiturates, antidepressive agents, Tylenol/codeine. The c² test found no significant difference between sociodemographic and occupational factors and drug consumption (p<.05, except for the work form (c²=18.08, gl=4, p=.001. However, violence rate showed a positive association with drug consumption (p<.05. This study found 126 cases of violence, 34 of which narrated their experience. Drug consumption and violence perception was identified in 2 categories: Conceptualization of Occupational Violence and Relationship between Violence and Drug Consumption.

  11. Evaluation of antidepressant activity of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol, a β-substituted phenylethylamine in mice. (United States)

    Dhir, Ashish; Malik, Sneh; Kessar, S V; Singh, K N; Kulkarni, S K


    forced swim test. Neurochemical analysis revealed that the molecule at 8 mg/kg., i.p. increased the levels of norepinephrine (21% increase) without affecting serotonin in the mouse brain. However, at higher dose (16 mg/kg., i.p.), it increased the levels of norepinephrine (13% increase), serotonin (37% increase), and dopamine (42% increase). The molecule enhanced the locomotor activity in mice only at higher doses. The molecule, unlike venlafaxine, which potentiated barbiturate-induced hypnosis, was devoid of any sedative activity. In conclusion, 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-yl)-cyclohexanol, possess antidepressant-like activity in animal models of depression by modulating the neurotransmitter levels in the brain. Such an activity might be due to the modulating action of this novel molecule on trace amine receptors. Such a molecule may be the future drugs of choice for the treatment of major depression. Copyright © 2010 Elsevier B.V. and ECNP. All rights reserved.

  12. Novas terapias para hipertensão endocraniana New therapies for intracranial hypertension

    Directory of Open Access Journals (Sweden)

    Arnaldo Prata Barbosa


    revisited, including pathophysiology, monitoring, the traditional approach, and also the presentation of recently proposed therapies. SOURCE OF DATA: The main medical literature data bases (especially Medline and Lilacs were searched for articles published in the last 10 years, and traditional text books and dissertations focusing the subject were consulted. SUMMARY OF THE FINDINGS: Intracranial hypertension may be associated with several cerebral neurologic lesions from traumatic, infectious or metabolic origin, and in severe cases may represent an important factor for morbidity and mortality. Increases in intracranial pressure interfere with cerebral blood flow; in order to maintain an adequate cerebral perfusion pressure, it is necessary to both reduce and control intracranial hypertension and combat low blood pressure from the very beginning of treatment. Adequate monitoring is essential, and the main points addressed in conventional management include elevation of the head of bed to 30° C, central positioning of the head, optimization of hypocapnia, perfect metabolic and hydro-electrolyte balance, sedation, anti-convulsive therapy, liquor drainage, and the use of barbiturics, mannitol and furosemide. New therapies currently under investigation include the use of dexanabinol, hypertonic saline solutions, moderate hypothermia, decompressive craniectomy, optimization of cerebral perfusion pressure, and reduction in cerebral microvasculature pressure (Lund therapy. CONCLUSIONS: The use of new therapies to effectively control intracranial hypertension, especially in cases that are refractory to the usual treatment, represent a promising scenario in the management of this problem.

  13. PCP (phencyclidine): an update. (United States)

    Garey, R E


    The steady rise in the promiscuous use of phencyclidine (PCP) as a "recreational" drug has recently gained nationwide attention because of the numerous violent and/or bizarre incidents caused by the use of this drug. Because the media often exaggerate reports of bizarre and violent behavior to make a "good" story, the potential PCP user may be tempted to ignore the media warnings. In the case of PCP, however exaggerated the story, a real danger does exist. So, despite numerous newspaper, radio and television warnings about the possible consequences of PCP use and abuse, the incidence of toxic reactions continues to climb. In many cases PCP is sold as other drugs, particularly THC, and in various colored capsules, tablets, liquids and crystals which may explain the increased usage despite the numerous warnings against its use. The advances in laboratory techniques and chemical processess have enabled the clandestine chemist to prepare relatively pure PCP and thus eliminate many of the toxic side effects due to impurities in the drug. In addition, 30 or more psychoactive PCP analogues have been developed and are starting to make an appearance on the street. PCP is perhaps the most potent psychotomimetic compound known at the present time and is capable of inducing a psychosis which is clinically indistinguishable from schizophrenia. The psychosis-producing effects of PCP are the most common toxic effects seen in hospital emergency rooms; but as the amount of PCP taken and/or the simultaneous involvement of other drugs, particularly barbiturates, occurs, severe medical problems (e.g., coma, seizures, respiratory arrest) begin to appear. Death from high doses of PCP or PCP plus other drugs does occur, but the principal cause of death from PCP abuse is due to trauma, homicide or suicide (usually of the bizarre or violent form). Young adult males, persons predisposed to mental illness and naive drug users appear to be the most susceptible to the adverse effects of PCP

  14. Estudo da fração inspirada de oxigênio na isquemia-reperfusão pulmonar em ratos Study of ventilation with different inspired oxygen concentration on lung ischaemia-reperfusion injury in rats

    Directory of Open Access Journals (Sweden)

    Rafael José Silveira


    / inspired oxygen fraction relation (PO2/FiO2, the level of reduced glutathione (GSH and barbituric acid substances reactive measure (TBARS in the lung tissue and the lung wet/dry weight ratio were used. RESULTS: The results showed that the ventilation with FiO2 at 0,21, when compared with the ventilation at 0,40 and 1,00 FiO2 during the ischaemia-reperfusion period, presented lower PAM, better PO2/FiO2 relation, higher values in the reduced glutathione measures, lower production of the TBARS and lower formation of lung edema. CONCLUSION: The ventilation with low FiO2 (0.21 showed better results when compared to those performed with higher FiO2 (0,40 and 1,00 on the lung ischaemia-reperfusion injury.

  15. A radioterapia profunda em doses elevadas na epilepsia focal: contrôle clínico e eletrencefalográfico

    Directory of Open Access Journals (Sweden)

    Paulo Pinto Pupo


    Full Text Available Radiotherapy in high doses has been used in cases of symptomatic epilepsy with the purpose of to act against the focal epileptic activity, as coadjuvancy to the common medical treatment. Patients with clinical manifestations of epilepsy in whom convulsive foci were demonstrated in the EEG, have been selected; these foci have been recognized as well localized and well circunscribed, and in all them the etiology has been the same (atrophic lesions, according to the clinical and radiological (craniogram, pneumoencephalogram and arteriogram examinations. The purpose of a so homogenous group was to study the results to be obtained in similar conditions. Twenty patients have been selected from a group of forty-eight, because it was possible to obtain a good follow-up for at least three months in each case. In all cases, a medical treatment (barbiturate plus hidantoi-nate has been used in uniform manner, with the purpose of avoiding influence on the judgement of the value of radiotherapy, for it was impossible to interrupt the drug therapy. Radiotherapy has been used in high doses over the epileptic lesion, which had been localized by the EEG. Two different techniques were used; in both 200 kv, 0.5 mm. filter of Cu were employed. Fourteen patients were irradiated in four different areas, of 4 cm. in diameter each one; they received 150 r daily, 2 areas by day, performing an average total of 3,000 r. In the other 6 cases the technique of kinetic convergent radiotherapy was employed, using the Siemens apparatus; each patient received, through a cutaneous area, an average doses of 3,000 r into the focus and 2,000 r in the skin; they received from 100 r to 150 r in the focus daily. Studying the twenty cases individually, there was marked EEG improvement in 4, relative improvement in 8 and no change in 8; there was marked decrease in the number of seizures in 8, relative decrease in 10 and no change in 2; the mental status was markedly improved in 7

  16. Anestesia por infusão contínua de propofol em cães pré-medicados com acepromazina e fentanil Anesthesia by continuous infusion of propofol in dogs premedicated with acepromazine and fentanyl

    Directory of Open Access Journals (Sweden)

    Jefferson da Silva Pires


    Full Text Available O propofol (2,6 diisopropilfenol é um agente hipnótico de ultra curta duração que produz sedação e hipnose similar aos barbitúricos, sendo desprovido de ação analgésica. Quimicamente, é o único agente anestésico venoso que pode ser usado tanto na indução como na manutenção anestésica. O presente trabalho objetivou avaliar freqüência cardíaca, respiratória, oximetria, pressão arterial média, volume minuto e volume corrente em cães pré-medicados com acepromazina e fentanil e anestesiados por infusão contínua de propofol. Dez cães foram submetidos à medicação pré-anestésica com acepromazina (0, e fentanil (0,, indução (3, e manutenção anestésica com propofol em infusão contínua por noventa minutos, na velocidade de 0, Os parâmetros foram mensurados imediatamente após a indução, 10, 20, 30, 60 e 90 minutos após; final da infusão e 30 minutos após o seu término. Os parâmetros foram analisados por análise de variância para valores repetidos e as médias foram analisadas pelo teste de Tuckey em nível de 5%. O protocolo utilizado não produziu variações estatisticamente significativas em nenhum dos parâmetros analisados. Um animal apresentou apnéia durante a indução. Embasado nesses resultados, verifica-se que o presente protocolo é seguro e eficaz para a realização de anestesia venosa em caninos.Propofol (2,6 diisopropylphenol is an ultra short duration hypnotic agent that produces sedation and hypnosis similar to barbituric agent, but lacks analgesic action. This is a chemically unique anesthetic agent that can be used for induction and anesthetic maintenance. The objective of this research was to evaluate the cardiac and respiratory rate, oximetry, mean arterial blood pressure and tidal volume and minute volume in dogs premedicated with acepromazine and fentanyl and anesthetized by continuous infusion by propofol. Ten dogs were submitted to

  17. Allodynia Is Associated With Initial and Sustained Response to Acute Migraine Treatment: Results from the American Migraine Prevalence and Prevention Study. (United States)

    Lipton, Richard B; Munjal, Sagar; Buse, Dawn C; Bennett, Alix; Fanning, Kristina M; Burstein, Rami; Reed, Michael L


    In a population sample of persons with migraine treating with a single category of acute migraine medication, to identify rates and factors associated with acute treatment outcomes, including 2-hour pain freedom (2hPF), 24-hour pain response (24hPR), and 24-hour sustained pain response (24hSPR). Key predictors include acute treatment type (triptans and other medication categories), the influence of allodynia on response to medication, and the interaction between medication category and presence of allodynia in response to treatment among people with migraine. Cutaneous allodynia was previously associated with inadequate 2hPF, 24hPR, and 24hSPR (sustained response at 24 hours among those with adequate 2hPF) among people with migraine in the American Migraine Prevalence and Prevention (AMPP) Study. The AMPP Study obtained data from a representative US sample of persons with migraine by mailed questionnaire. The 2006 survey included 8233 people with migraine aged 18 or over who completed the Migraine Treatment Optimization Questionnaire (mTOQ). mTOQ was used to assess acute treatment outcomes including 2hPF, 24hPR, and 24hSPR. Eligible individuals used only a single category of acute prescription migraine treatments (n  =  5236, 63.6%). This sample was stratified into 5 categories of type of acute prescription headache medication used (triptans, nonsteroidal anti-inflammatory drugs, barbiturate-combinations, opioids, and opioid combinations and ergot alkaloids). Separate binary logistic regression models evaluated: (1) triptans vs other medication types; (2) presence of allodynia vs no allodynia; and (3) the interaction of medication category with allodynia. Sociodemographic variables, health insurance status, over-the-counter and preventive medication use were included as covariates. Odds ratios (OR) and 95% confidence intervals (CI) were generated for each acute treatment outcome. Among eligible participants, the mean age was 46 years, and 82.5% were women

  18. Uso de substâncias psicoativas entre universitários de medicina da Universidade Federal do Espírito Santo Psychoactive substance use among Medicine students from Espirito Santo Federal University

    Directory of Open Access Journals (Sweden)

    Denis Soprani Pereira


    prevalence of alcohol was founded (86.9%, followed by tobacco (22.0%, solvents (15.5%, amphetamines (10.1%, cannabis (9.5%, hallucinogens (1.8% and barbiturates (0.6%. CONCLUSION: It is necessary to prevent the psychoative substance abuse among college students, introducing curricular disciplines on the theme or specific programs to attend these students.

  19. Circadian characteristics of serum calcium, magnesium and eight trace elements and of their metallo-moieties in urine of healthy middle-aged men. (United States)

    Kanabrocki, E L; Sothern, R B; Ryan, M D; Kahn, S; Augustine, G; Johnson, C; Foley, S; Gathing, A; Eastman, G; Friedman, N; Nemchausky, B A; Kaplan, E


    To monitor the around-the-clock distribution of serum and urine concentrations of calcium, magnesium and eight trace elements and of those same elements in urine after their dialysis, and to statistically describe their circadian characteristics by chronobiological procedures. Serum and urine samples were collected every 3h over a single 24h period from eleven clinically-healthy male subjects, 41-60 years of age, and were analyzed for calcium (Ca), magnesium (Mg), iron (Fe), copper (Cu), zinc (Zn), lead (Pb), cadmium (Cd), cobalt (Co), chromium (Cr), and nickel (Ni). Urines were also sequentially dialyzed against ammonium-barbituric acid buffer at pH 7.35+/-0.02 using a 12.000-14.000 molecular weight exclusion sieve and then reanalyzed for the same elements. Urine concentrations were adjusted by urine volume to reflect a 3h excretion rate. Time-series were analyzed for circadian time-effect by ANOVA and for rhythm characteristics by the single cosinor fitting procedure. The dialysis effectively removed 90% of total solids, 97% of urea, 92% creatinine, 72% uric acid, and essentially all of glucose. It also removed 99% of potassium (K), 96% of sodium (Na), 65% of Ca and P, 55% of Mg, 41% of Zn and 88% of Ni. A significant or borderline-significant 24h rhythm in serum was detected for Ca, Mg, Fe, Cu, Zn, Cd and Cr; in untreated urine for Ca, Fe, Cu, Zn, Ni, creatinine and volume; and in dialyzed urine for Ca, Fe, Cu, Zn, Pb, Cr, Cd and Ni. A 12h component was significant or borderline-significant in serum for Mg, Fe, Zn, and Cd; in untreated urine for volume, creatinine, Ca, Mg, Cu, and Ni; and in dialyzed urine for Ca, Mg, Fe, Cu, Zn, and Cr. In general, values in serum were lowest near the onset of sleep and highest in the first half of the day (between 02:28 and 13:56 h), while highest values in untreated or dialyzed urine were found several hours later in the day and at night. Significant circadian variations were found in levels of nearly every element that was

  20. Comparative study of drug use among undergraduate students at the University of São Paulo: São Paulo campus in 1996 and 2001 Estudo comparativo entre 1996 e 2001 do uso de drogas por alunos da graduação da Universidade de São Paulo: Campus São Paulo

    Directory of Open Access Journals (Sweden)

    Vladimir de Andrade Stempliuk


    Full Text Available OBJECTIVE: To compare the rate of drug use prevalence and to investigate opinions regarding such use among undergraduate students at the University of São Paulo - São Paulo campus in 1996 and again in 2001. METHODS: Both studies followed the same procedures of sampling and data collection. A random sample of undergraduate students, divided into the areas Humanities, Exact Sciences and Biologic Sciences, responded to an anonymous and self-report survey regarding the use of licit and illicit drugs within the last 30 days, within the last 12 months and over the lifetime of the subject. The two surveys were compared through the construction of (95% confidence intervals for the prevalence differences for each substance by area and by total number of students. The Wald test for homogeneity was applied in order to compare the prevalences. RESULTS: High approval of regularly trying and using cocaine, crack, amphetamines and inhalants was observed. The drugs that showed statistic significant increasing were:lifetime use: alcohol, tobacco, marijuana, inhalants, hallucinogens, amphetamines, anticholines, barbiturics and any illicit drug;last-12-month use: marijuana, inhalants, amphetamines, hallucinogens and any illicit drug;last-30-day use: marijuana, inhalants, amphetamines and any illicit drug. DISCUSSON: The observed difference in the use of some drugs between the two surveys appears to be a consequence of the higher rates of favorable opinions regarding trying and regularly using some psychoactive substances, a finding that mirrors global trends in drug use.OBJETIVO: Esta pesquisa teve como objetivo comparar as prevalências de uso de diversas drogas e as opiniões sobre esses usos entre estudantes de graduação da Universidade de São Paulo (USP nos anos de 1996 e 2001. MÉTODOS: Os dois estudos seguiram as mesmas metodologias de amostragem e coleta de dados. Os alunos foram randomicamente selecionados de acordo com suas áreas de estudo (Biol

  1. Gestational Pityriasis Rosea: Suggestions for Approaching Affected Pregnant Women. (United States)

    Monastirli, Alexandra; Pasmatzi, Efstathia; Badavanis, George; Tsambaos, Dionysios


    pityriasis rosea, for intrauterine fetal death. All miscarrying women reportedly revealed an aggressive course of widespread eruption and severe constitutional symptoms; all of them had HHV-6 DNA in the plasma, placenta, skin lesions, and fetal tissues, whereas HHV-7 DNA was detected in the plasma and skin lesions in 3 out of 8 (37.5%) miscarrying women. HHV-6 DNA was found only in the plasma of 2 out of 31 women (6.45%) with normal pregnancy, whereas HHV-7 DNA was detected in the plasma of 3 (9.45%) and in the skin lesions of 2 women (6.45%) with normal pregnancy. The total abortion rate in women who developed pityriasis rosea during their pregnancy (13%) does not differ from that observed in the general population. Nevertheless, it is markedly higher in cases affected during the first 15 gestational weeks (57%) (4,5). Surprisingly, this devastating impact of pityriasis rosea on the outcome of pregnancy is almost completely unknown not only to the public but also to many members of the medical community. It is also largely unknown that, particularly during the first 15 gestational weeks, all pregnant women should avoid any contact with patients known to have pityriasis rosea. Since we have received a considerable number of requests for consultation with pregnant women with pityriasis rosea over the last few years, our group has compiled suggestions approaching the affected patients: 1. If an eruption suggestive for pityriasis rosea occurs in a pregnant woman, the following factors should be excluded: a. Exposure to drugs prior to the development of the rash (biologic agents, captopril, clonidine, hydrochlorothiazide, atenolol, lamotrigine, nortriptyline, barbiturates, metronidazole, terbinafine, omeprazole, non-steroidal anti-inflammatory drugs, and isotretinoin), which are capable of inducing a pityriasis rosea-like eruption (6) and b. Disorders included in the differential diagnosis (syphilis and infections due to parvovirus, herpes virus, cytomegalovirus, and Epstein

  2. Historical development of modern anesthesia. (United States)

    Robinson, Daniel H; Toledo, Alexander H


    in 1937. He was the first to describe the routinely placing of the tip of his newly re-designed laryngoscope in the epiglottic vallecula which is attached to the base of the tongue, thus when lifted exposed the entire larynx. Macintosh was genuinely astonished at what a great view he could achieve with his new blade and technique. The use of barbiturates as an intravenous anesthetic began in 1932. Sodium thiopental gained popularity after its use was described in detail by a Dr. John Lundy (1894-1973) of the Mayo Clinic. Other I.V. medications were tried over the past seventy years, but the newest induction drug which provided for a substantially shorter recovery period and seemed to actually suppress laryngeal reflexes has brought with it many benefits. Propofol, introduced clinically in 1977, demonstrated many positive effects even as an anti-emetic compound. Before October of 1846, surgery and pain were synonymous but not thereafter. As we entered the information age where the infrastructure of evidence based medicine and newer fields of genetics, transplantation, imaging radiology and even stem cells became quickly integrated into mainstream medicine, we can predict an excellent future on the progress to be made in anesthesia.

  3. Anestesia venosa total em regime de infusão alvo-controlada: uma análise evolutiva Anestesia venosa total en régimen de infusión objeto controlada: un análisis evolutivo Total intravenous anesthesia as a target-controlled infusion: an evolutive analysis

    Directory of Open Access Journals (Sweden)

    Fernando Squeff Nora


    ón objeto controlada (IOC. El primer modelo farmacocinético descrito para uso en IOC, fue descrito por Schwilden en 1981. Quedó demostrado a partir de entonces, que era posible mantener la concentración plasmática deseada de un fármaco utilizando bomba de infusión por computador. CONTENIDO: Este artigo quiso dejar sentadas las bases teóricas de la IOC, presentar una propuesta de desarrollo de un vocabulario común en IOC todavía no publicado en Brasil y hacer un análisis crítico de los aspectos actuales de la IOC en el mundo y en Brasil. CONCLUSIONES: La llegada de nuevas bombas de infusión dotadas de los modelos farmacocinéticos del remifentanil, sufentanil y propofol inaugura otro capítulo de la AVT y coloca a Brasil a tono con la tendencia mundial en IOC. Esos sistemas facilitarán la IOC de hipnóticos y opioides concomitantemente. La conclusión más importante, sin embargo, se refiere a la economía en la medida en que los fármacos utilizados en esas bombas no quedarán restrictos a solamente una empresa farmacéutica, como por ejemplo lo que ocurrió con el propofol. Hoy ya disponemos de equipos para la utilización de propofol y opioides en IOC, que aceptan cualquier presentación farmacéutica con la ventaja de poder alterar la concentración del fármaco en la jeringuilla de acuerdo con la dilución que se desee.BACKGROUND AND DOBJECTIVES: Total intravenous anesthesia (TIVA has seen several developments since it was first used. Since the synthesis of the first intravenous anesthetics, with the introduction of barbiturates (1921 and thiopental (1934, TIVA has evolved until the development of TIVA with target-controlled infusion pumps (TCI. The first pharmacokinetic model for the use of TCI was described by Schwilden in 1981. From that moment on, it was demonstrated that it is possible to maintain the desired plasma concentration of a drug using an infusion pump managed by a computer. CONTENTS: The objective of this report was to describe the

  4. Erythrogram, oxidative stress and mineral interaction in naturally infected lambs supplemented with different forms of oral ironEritrograma, estresse oxidativo e interação mineral em cordeiros naturalmente infectados por parasitas gastrintestinais suplementados com diferentes formas de ferro oral

    Directory of Open Access Journals (Sweden)

    Marta Lizandra Rêgo Leal


    Full Text Available The present study aimed to assess the oxidative profile, erythrogram and mineral interaction in lambs with anemia due to worm infection supplemented with different forms of oral iron. It was used 27 lambs, 6 to 8 month old, naturally infected by Haemonchus contortus, which showed packed cell volume between 16 and 18%. The animals were divided in three groups: Control Group (GC n=9, Ferrous Sulphate Group (G2 n=9 and Ferric Sulphate Group (G3 n=9. The animals of G2 received 1 g of ferrous sulphate (Fe+2 orally daily, equivalent to 200 milligram of iron, the animals of G3 received 1 g of ferric sulphate (Fe+3 orally daily, or equivalent to 200 milligram of iron, whereas the GC received no treatment. The samples were taked on day 0, 7, 14, 21 and 28 of the experiment, and during four days two animals of each group were kept in metabolic cages to measure the faecal minerals excretion. There was no difference among the groups about serum iron values and parameters of red blood cells. The serum copper and zinc values were lower in the G2 and G3 on days 21 and 28 of the experiment, whereas the faecal copper, iron and zinc excretion was higher in the same groups. The superoxide dismutase (SOD levels were lower in the G2 and G3 on day 28 whereas the levels of non-protein thiol groups (NPTH showed a decrease on days 21 and 28. In relation to reactive species thio-barbituric acid (TBARS, there was an increase on day 28 in the G2 and G3. Based on these results, it was concluded that the oral supplementation with 200 mg of iron, irrespective of its form, ferrous or ferric, does not increase the erythrocyte response in lambs. As well as, it has antagonist action on copper and zinc, reducing its serum concentrations and increasing the faecal excretion of these minerals. Moreover, the decrease of the serum copper and zinc concentrations causes a decrease in activity of superoxide dismutase, causing an oxidative stress situation.O presente estudo teve por

  5. Recorrência da Crise Convulsiva após Terapia Anticonvulsivante com Sulfato de Magnésio em Pacientes com Eclâmpsia Recurrence of Seizures after Anticonvulsant Therapy with Magnesium Sulfate in Patients with Eclampsia

    Directory of Open Access Journals (Sweden)

    Melania Maria Ramos de Amorim


    . Patients and Methods: a prospective cohort study was conducted, enrolling all cases of eclampsia managed at IMIP between January/1995 and June/1998. Magnesium sulfate and oxygen therapy were administered routinely and interruption of pregnancy was performed after maternal stabilization. The frequency of recurrence of seizures and its association with maternal complications were determined. chi² test for association was used at a 5% level of significance. Results: twelve cases presented recurrence of convulsions after magnesium sulfate (10% and all received a repeated dose. In four of them convulsions persisted and they received intravenous diazepam. After diazepam, one patient still had seizures, with unsuccessful administration of phenytoin and therefore barbituric coma was induced (thionembutal. This patient had a CT-scan with evidence of intracerebral hemorrhage. Maternal complications were significantly more frequent in the group with recurrence: coma (16.7% versus 0.95, acidosis (50% versus 2.9%, pulmonary edema (16.7% versus 2.9%, cerebral hemorrhage (16.7% versus 0% and acute renal failure (16.7% versus 1.9%. Three cases of maternal death occurred in patients with recurrence (25% versus 2 cases in patients without recurrence (1.9%. Conclusions: rate of recurrence after anticonvulsant therapy with magnesium sulfate is low (10% but it is associated with increased maternal morbidity and mortality. These cases must be managed in an intensive care unit and submitted to routine CT-scan because cerebral hemorrhage can be the cause of recurrence.

  6. Considerações a propósito do tratamento medicamentoso de 1217 pacientes epilépticos: I: estudo em relação ao tipo de epilepsia e ao eletrencefalograma Drug treatment of 1.211 epileptic patients: I — study regarding the clinical manifestations and eletroencephalographic patterns

    Directory of Open Access Journals (Sweden)

    Luís Marques-Assis


    direito foram os que apresentaram, percentualmente, menor índice de remissão.The evolution of 1.217 epileptic patients submitted to antiepileptic drug treatment is studied. Barbiturates, hydantoin, primidone and trimethadione were administered to the patients, isolated or in association. The study was made in regard to the clinical manifestations and electroencephalographic pattern. Concerning the type of seizures, the author draws the following conclusions : 1 the evolution was better in patients with Bravais-Jackson seizures; 2 the highest percentual rate of remission was shown by patients with sleep seizures (59,0%; 3 the patients with "grand mal" seizures without aura were the most refractory to the treatment; 4 the patients with generalized fits secondary to focal discharges showed the best results, although evidencing lowest remission index; 5 among all types of seizures, the Bravais-Jacsonian fits showed better evolution, specially the cases without generalization; 6 significant differences of evolution were not found between convulsive and non convulsive epilepsy. The electroencephalographic study led the author to the following conclusions: 1 the evolution was better in cases with normal EEG; 2 the evolution was better in cases with paroxystic, bilateral and synchronic dysrhythmia than in cases with diffuse abnormalities in sensu latu and with focal abnormalities; 3 the patients with temporal dysrhythmia showed the lowest remission index; 4 the patients with unilateral temporal dysrhythmia showed better evolution than those with bilateral temporal dysrhythmia; 5 the patients with right temporal dysrhythmia presented the lowest remission index.

  7. Use of psychoactive drugs and related falls among older people living in a community in Brazil Uso de medicamentos psicoativos e seu relacionamento com quedas entre idosos

    Directory of Open Access Journals (Sweden)

    Flávio Chaimowicz


    Full Text Available INTRODUCTION: Population aging in Brazil has increased the prevalence of neurodegenerative diseases (Parkinson's and Alzheimer's disease and affective disorders (anxiety, depression, all common in old age. A retrospective study was carried out with the purpose of ascertaining if there is an association between falls and psychoactive medication use among older residents of a community in Brazil. METHODS: All residents aged 65+ (n=161 of one neighborhood of Campo Belo, Brazil (population of 48,000 were evaluated regarding the use of psychoactive drugs and the occurrence of falls in the 12 months preceding the study. Vision and hearing screenings were also performed. RESULTS: From the study population, 9.3% were taking prolonged half-life benzodiazepines, 4.4% anticonvulsants (mostly barbiturates, 2.5% antidepressants (all cyclics and 8.1% alpha-methyldopa. No subject reported use of hypnotics, neuroleptics or drugs to treat Alzheimer's or Parkinson's diseases (except biperiden. As a whole, drugs that increase the risk of falls were used by 1/5 of this population. In the 12-month period preceding the study, 27 residents (16.8% experienced falls and, of those, 4 (14.8% had fracture(s. There was an independent association between psychoactive drug use and falls when variables such as age, gender, vision and hearing were controlled (p=0.02. CONCLUSIONS: Although the population of this neighborhood must be considered young (only 4% are 65 years old or more, there are already problems related to the use of psychoactive drugs among people. Prescribed anxiolytics, anticonvulsants, antidepressants and antihypertensives are not appropriate for this age group and their use is associated with falls.INTRODUÇÃO: O envelhecimento populacional no Brasil tem aumentado a prevalência de doenças neurodegenerativas (Parkinson, Alzheimer e psiquiátricas (depressão, ansiedade, comuns em idosos. Realizou-se estudo retrospectivo com o objetivo de determinar se h

  8. Consumo de substâncias psicoativas por adolescentes escolares de Ribeirão Preto, SP (Brasil. I - Prevalência do consumo por sexo, idade e tipo de substância The consumption of psychoactive substances by adolescents in schools in an urban area of Southeastern region of Brazil. I - Prevalence by sex, age and kind of substance

    Directory of Open Access Journals (Sweden)

    Gilson M. Muza


    pelos meninos como pelas meninas, muitas vezes em idades bem precoces.INTRODUCTION: Concern over the consumption of psychoactive substances by teenagers has given rise to a great wordwide effort to produce information about this phenomenon. This study set out to investigate the prevalence of consumption of legal and illegal psychoactive substances, its distribution by age, sex and age at first experience of them, among teenage pupils in county, Ribeirão Preto, SP, Southeastern Brazil. MATERIAL AND METHOD: A self-applicable questionnaire duly adapted and submitted to a reliability test was applied to a proportional sample of 1,025 teenagers enrolled in 8th, 9th, 10th and 11th grads at public and private city schools. The questionnaire contained questions about the use of ten classes of psychoactive substances, demographic questions and validation information, as well as questions about the perception and intrinsic behavior related to drug consumption. RESULTS: The sample of 88.9% had consumed alcoholic beverages sometime in their lives, 37.7% had used tobacco, 31.1% solvents, 10.5% medicines, 6.8% marihuana, 2.7% cocaine, 1.6% hallucinogens, and 0.3% of the sample had consumed some opiate substance. The rates of consumption increased with age for all substances; however, the use of tobacco and of illegal substances was less intense during the later years of adolescence. As to sex distribution, boys consumed more than girls, except for medicines, with girls consuming barbiturates, amphetamines and tranquilizers in proportions similar to or higher than those observed among boys. Age at first experience showed that access to psychoactive substances occurred at very early ages. CONCLUSIONS: Experimenting with psychoactive substances, whether legal or illegal, is a frequent phenomenon during adolescence, both among boys and girls, often at very early ages.

  9. Prevalência do consumo de drogas na FEBEM, Porto Alegre Drug use prevalence at FEBEM, Porto Alegre

    Directory of Open Access Journals (Sweden)

    Maristela Ferigolo


    já terem utilizado drogas ilícitas.OBJECTIVE: This study aimed to determine the prevalence of drug use among institutionalized children and adolescents; to assess the degree of associated use of illicit drugs with alcohol and tobacco; and to determine which is the gateway drug to illicit drug use. METHODS: A cross-sectional study was carried out in the Fundação Estadual do Bem-Estar do Menor, in Porto Alegre (FEBEM Southern Brazil. A questionnaire developed by the World Health Organization to determine prevalence off drug use was answered anonymously by a population of literate minors who were in FEBEM because of delinquency or due to social risk. The analysis aimed to describe the frequency of use of each drug and relate it to gender, age of beginning, and reason of institutionalization. RESULTS: A total of 382 participants answered the questionnaire. The substances most frequently used on an experimental basis were: alcohol (81,3%, tobacco (76,8%, marijuana (69,2%, cocaine (54,6%, inhalants (49,2%, anxiolytic drugs (13,4%, hallucinogens (8,4%, amphetamines (6,5% and barbiturates (2,4%. Overall, around 80% of the respondents reported having used some illicit drug at least once in the past. Licit drugs, like alcohol and tobacco, were used mainly by males, while medicines were used mostly by females. Adolescents with delinquency records showed a significantly higher frequency of alcohol, marijuana, cocaine, and solvent use. The mean age of beginning was under 12 years for alcohol and tobacco use, under 13 years for marijuana and inhalants, and under 14 years for cocaine. Concomitant use of illicit and licit drugs was found to be high in this population. CONCLUSIONS: A high prevalence of precocious drug use was found among institutionalized children and adolescent, with alcohol and tobacco being used earlier than illicit drugs. Delinquent males were more likely to have used illicit drugs.

  10. Sedação e analgesia em neonatologia Sedación y analgesia en neonatología Sedation and analgesia in neonatology

    Directory of Open Access Journals (Sweden)

    Yerkes Pereira e Silva


    dolor en Unidades de Terapia Intensiva Neonatal y también para hacer el ambiente más humanizado y menos estresante para los pacientes y sus familiares. El tratamiento del dolor en el recién nacido consiste en medidas no farmacológicas (succión no nutritiva, glicosis y farmacológicas (analgésicos no-opioides, opioides y anestésicos locales. La sedación en recién nacidos es producida por fármacos que actúan disminuyendo la actividad, la ansiedad y la agitación del paciente, pudiendo conllevar a la amnesia de eventos dolorosos o no dolorosos. La sedación puede ser hecha a través del uso de hidrato de cloral, barbitúricos, propofol y benzodiazepínicos. CONCLUSIONES: La prevención del dolor y la indicación de analgesia deben ser individualizadas y siempre consideradas en todos los recién nacidos portadores de enfermedades potencialmente dolorosas y/o sometidos a procedimientos invasivos, quirúrgicos o no.BACKGROUND AND OBJECTIVES: The study of pain in neonatology is important because pain and stress mean suffering and discomfort for newborns and, despite it, very little has been done to minimize them. In this revision we discuss: prevention of pain, non-pharmacological and pharmacological treatment, and sedation in newborns. CONTENTS: Several non-pharmacological measures can be taken to prevent pain in Neonatal Intensive Care Units, and to humanize and reduce the stress on the environment for patients and their families. Pain treatment in the newborn consists of non-pharmacological (non-nutritive suckling, glucose and pharmacological (non-opioid analgesics, opioids, and local anesthetics measures. Sedation in the newborn is achieved with drugs that decrease activity, anxiety, and agitation of the patient, and that could lead to amnesia of painful and non-painful events. Sedation can be accomplished with chloral hydrate, barbiturates, propofol, and benzodiazepines. CONCLUSIONS: Prevention of pain and the indication of analgesia should be individualized

  11. Vladimir Prelog i Zavod za organsku kemiju

    Directory of Open Access Journals (Sweden)

    Jakopčić, K.


    -operation from the small but prosperous pharmaceutical company "Kaštel" in Zagreb. On behalf of the agreement, Prelog and his department obtained funds to fit up the laboratory and to start very prosperous research in the synthesis and studies of pharmaceutically interesting compounds. With his assistants, students and other collaborators, Prelog started research of cinchona bark alkaloids, preferentially oriented to the synthesis of quinine. For example, Prelog's method of double intramolecular alkylation to synthetize the quinuclidine moiety of quinine was patented by "Kaštel". With R. Seiwerth he developed the first useful synthesis of adamantane. Prelog's group started research in the field of sulphonamides and commercial success of "Streptazole" stimulated the development of the research laboratories within "Kaštel". The collaboration in the research continued in fields of other chemotherapeutics, analeptics, spasmolitics, barbiturates etc. Within the period 1935-1941, Prelog published 48 scientific papers and 8 patents. In less than seven years, his results enormously influenced the entire organic chemistry in Zagreb till nowadays. Under the confused and uncertain circumstances caused by the beginning of World War II, Prelog left Zagreb in 1941 and continued his extraordinary scientific career at the ETH in Zürich.During the war (1942-1945 the tuition and the Department were run by Dr. Rativoj Seiwerth, former collaborator and first assistant to V. Prelog. In almost unbelievable conditions, the young assistant, then assistant professor (since January 1943, R. Seiwerth fully succeeded in continuing most activities founded by Professor Prelog. After the war (1945, R. Seiwerth was forced to resign. Nevertheless, soon after R. Seiwerth continued his research work, firstly in the Institute for Industrial Research in Zagreb (1946-1952, and later in the Research Institute of "Pliva" in Zagreb. He retired in 1980.In post-war conditions (1945/46, the activity of the Technical

  12. A serendipidade na medicina e na anestesiologia A serendipidade en la medicina y en la anestesiologia Serendipity in medicine and anesthesiology

    Directory of Open Access Journals (Sweden)

    Nilton Bezerra do Vale


    biología, anatomía, física, química, fisiología, farmacología, astronomía, arqueología y... mucha suerte. CONCLUSIONES: Aunque accidentes en la pesquisa y en la sala de operación sean lamentables, hay aquéllos que acontecen y, a veces, pueden llevar a avances espectaculares, como tratamientos heroicos y hasta Premios Nobel. Mantener la mente abierta es un trazo común a aquellos que desean contar con la gran suerte, como afirmaba el físico americano Henry (1842: "Las semillas del hallazgo flotan constantemente alrededor nuestro, pero apenas lanzan raíces en las mentes bien preparadas para recibirlas".BACKGROUND AND OBJECTIVES: This study has evaluated more than a hundred of the most fortunate couplings of a brilliant mind with fortunate luck (serendipity, through the re-reading of most relevant histories on science-related (n = 46 and anesthesiology-related (n = 16 inventions and discoveries. CONTENTS: This educational article encourages anesthesiologists to appreciate events related to scientific inventions and discoveries, showing that serendipity is possible, provided it is expected. Each discovery or invention includes history, references and scientific or anecdotal explanation. In addition to traditional discoveries, such as wine, gravity, photograph, Velcro, airbag, etc., there are other Medicine-related (microscope, X-rays, vaccine, penicillin, insulin, laser, Paps smear, etc. and Anesthesiology-related (isometry, gloves, N2O, ether, barbiturates, benzodiazepines, blood patch, etc. discoveries. Creativity and serendipity may act as cornerstones for clinical and basic research of pioneer inventions for medical and anesthesiologic advances. In fact, topics related to biology, anatomy, physics, chemistry, physiology, pharmacology, astronomy and archeology should be master and … lots of luck. CONCLUSIONS: Although research and operating room accidents are regrettable, some of them happen and may sometimes lead to spectacular advances, such as heroic

  13. High perfomance liquid chromatography in pharmaceutical analyses. (United States)

    Nikolin, Branko; Imamović, Belma; Medanhodzić-Vuk, Saira; Sober, Miroslav


    electrochemical detection is nearly always associated with a major frontal peak than tails considerably. To date, the most sensitive method has been the reductive electrochemical detection and giving the excellent results in the investigation on some classes of drugs. Several high performance liquid chromatography oxidative electrochemical methods have been developed for the analyses of drugs and metabolites in body fluids. Mass spectrometer as specific detector with all variation of ionisation and interface (thermo spray, moving belt etc. ) or liquid chromatography-tandem mass spectrometry2,3,4,5). NMR as selective and specific detector in high performance liquid chromatography today is also in used. The development of a non-aqueous eluent for ion-exchange separation on silica has provided an excellent system which, when used in conjugation with an electrochemical detector, permits the analyses of an extensive range of especially basic drugs and metabolites. New packing materials such as polymeric, base deactivated silica's, pyrolysed carbon and the internal surface packing should offer the improved stability and higher efficiencies for certain classes of the compounds such as basic drugs. Microbore columns should become more accepted since they offer not only improved sensitivity but also a lower solvent consumption and consequently the reduced needs to dispose of noxious solvents. Many analyses of basic drugs are still performed by the same method of the ion-exchange chromatography on unmodified silica columns with an eluent buffered to about pH 9. Neutral or weakly acidic drugs for instance barbiturates can be chromatographed on a reversed phase system whilst acidic drugs for example paracetamol, cannabis are separated either by ion suppression or ion-pair chromatography on a reversed-phase packing material. In micelar liquid chromatography micelar mobile phases in reversed-phase instead of conventional hydro organic mobile phase is used. In micelar liquid chromatography

  14. Prevention of suicide and attempted suicide in Denmark. Epidemiological studies of suicide and intervention studies in selected risk groups. (United States)

    Nordentoft, Merete


    The suicide rates in Denmark have been declining during the last two decades. The decline was relatively larger among women than among men. All age groups experienced a decline except the very young with stable rates and the very old with increasing rates. The Universal, Selective, Indicated (USI) model recommended by Institute of Medicine was used as a framework for the thesis. Universal preventive interventions are directed toward the entire population; selective interventions are directed toward individuals who are at greater risk for suicidal behaviour; and indicated preventions are targeted at individuals who have already begun self-destructive behaviour. At the universal level, a review was carried out to highlight the association between availability of methods for suicide and suicide rate. There were mostly studies of firearms, and the conclusion of the review was that there was clear indication of restricted access to lethal means was associated with decline in suicide with that specific method, and in many cases also with overall suicide mortality. Restricting access is especially important for methods with high case fatality rate. Our own study indicated a beneficial effect on suicide rates of restrictions in access to barbiturates, dextropropoxyphen, domestic gas and car exhaust with high content of carbon monoxide. Although a range of other factors in the society might also be of importance, it was concluded that restrictions in access to dangerous means for suicide were likely to play an important role in reducing suicide rates in Denmark, especially for women. At the selective level, there are several important risk groups such as psychiatric patients, persons with alcohol and drug abuse, persons with newly diagnosed severe physical illness, all who previously attempted suicide, and groups of homeless, institutionalized, prisoners and other socially excluded persons. The thesis focused on homeless persons and psychiatric patients, especially patients