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Sample records for human butyrylcholinesterase administered

  1. Human butyrylcholinesterase polymorphism: Molecular modeling.

    Science.gov (United States)

    Lushchekina, S; Delacour, H; Lockridge, O; Masson, P

    2015-01-01

    Prolonged apnoea following injection of ester-containing myoralaxants was first described in 1953. Because a large part of administered succinylcholine is shortly hydrolyzed by plasma butyrylcholinesterase (BChE) under normal conditions, prolonged apnoea was attributed to deficiency in BChE. It was found that BChE deficiency was due to genetic variations. Human BChE gene shows a large polyallelism. About 75 natural mutations of the BCHE gene have been documented so far [1]. Most of them cause alteration in BChE activity through point mutation effect on catalytic activity. Frame shifts and stop codons may also affect expression, or cause truncations in the sequence. Recently, two novel BChE "silent" variants, Val204Asp [2] and Ala34Val [3], causing prolonged neuromuscular block after administration of mivacurium, were discovered. Mutations were genetically and kinetically characterized. The aim of the current study was to understand how these mutations determine "silent" phenotype. Molecular dynamics studies were carried out with NAMD 2.9 software at the Lomonosov supercomputer. Charmm 36 force field was used, periodical boundary conditions, 1 atm pressure, 298 K. 100 ns molecular dynamics runs were performed for the wild-type BChE and its mutants Val204Asp and Ala34Val. Unlike wild-type BChE, which retained its operative catalytic triad through the whole MD simulation, the catalytic triad of mutants was disrupted, making chemical step impossible. Val204Asp mutation leads to reorganization of hydrogen bonding network around the catalytic triad, which in turn increases the distance between catalytic residue main chains. Mutation Ala34Val, located on the protein surface, leads to increased fluctuations in the Ω-loop and subsequent disruption of the gorge structure, including disruption of the catalytic triad and formation of new hydrogen bonds involving catalytic center residues. Comparative study of the "silent" Ala328Asp mutant and the catalytically active mutant

  2. Expression of Recombinant Human Butyrylcholinesterase

    National Research Council Canada - National Science Library

    Lockridge, Oksana

    1997-01-01

    .... The G117H enzyme has the potential to be useful for decontamination of skin and eye. To determine how many amino acids could be deleted from butyrylcholinesterase without loss of activity, deletion mutants were expressed...

  3. Tissue distribution of human acetylcholinesterase and butyrylcholinesterase messenger RNA

    Energy Technology Data Exchange (ETDEWEB)

    Jbilo, O.; Barteles, C.F.; Chatonnet, A.; Toutant, J.P.; Lockridge, O.

    1994-12-31

    Tissue distribution of human acetyicholinesterase and butyryicholinesterase messenger RNA. 1 Cholinesterase inhibitors occur naturally in the calabar bean (eserine), green potatoes (solanine), insect-resistant crab apples, the coca plant (cocaine) and snake venom (fasciculin). There are also synthetic cholinesterase inhibitors, for example man-made insecticides. These inhibitors inactivate acetyicholinesterase and butyrylcholinesterase as well as other targets. From a study of the tissue distribution of acetylcholinesterase and butyrylcholinesterase mRNA by Northern blot analysis, we have found the highest levels of butyrylcholinesterase mRNA in the liver and lungs, tissues known as the principal detoxication sites of the human body. These results indicate that butyrylcholinesterase may be a first line of defense against poisons that are eaten or inhaled.

  4. Flavonoids as Inhibitors of Human Butyrylcholinesterase Variants

    Directory of Open Access Journals (Sweden)

    Maja Katalinić

    2014-01-01

    Full Text Available The inhibition of butyrylcholinesterase (BChE, EC 3.1.1.8 appears to be of interest in treating diseases with symptoms of reduced neurotransmitter levels, such as Alzheimer’s disease. However, BCHE gene polymorphism should not be neglected in research since it could have an effect on the expected outcome. Several well-known cholinergic drugs (e.g. galantamine, huperzine and rivastigmine originating from plants, or synthesised as derivatives of plant compounds, have shown that herbs could serve as a source of novel target-directed compounds. We focused our research on flavonoids, biologically active polyphenolic compounds found in many plants and plant-derived products, as BChE inhibitors. All of the tested flavonoids: galangin, quercetin, fisetin and luteolin reversibly inhibited usual, atypical, and fluoride-resistant variants of human BChE. The inhibition potency increased in the following order, identically for all three BChE variants: luteolin

  5. Delipidation of Plasma Has Minimal Effects on Human Butyrylcholinesterase

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    Seda Onder

    2018-02-01

    Full Text Available Human butyrylcholinesterase (BChE is purified in large quantities from Cohn fraction IV-4 to use for protection against the toxicity of chemical warfare agents. Small scale preliminary experiments use outdated plasma from the American Red Cross as the starting material for purifying BChE (P06276. Many of the volunteer donor plasma samples are turbid with fat, the donor having eaten fatty food before the blood draw. The turbid fat interferes with enzyme assays performed in the spectrophotometer and with column chromatography. Our goal was to find a method to remove fat from plasma without loss of BChE activity. Satisfactory delipidation was achieved by adding a solution of 10% dextran sulfate and calcium chloride to fatty plasma, followed by centrifugation, and filtration through a 0.8 μm filter. Treatment with Aerosil also delipidated fatty plasma, but was accompanied by loss of 50% of the plasma volume. BChE activity and the BChE isozyme pattern on nondenaturing gel electrophoresis were unaffected by delipidation. BChE in delipidated plasma was efficiently captured by immobilized monoclonal antibodies B2 18-5 and mAb2. The immunopurified BChE was released from antibody binding with acid and visualized as a highly enriched, denatured BChE preparation by SDS gel electrophoresis. In conclusion, delipidation with dextran sulfate/CaCl2 preserves BChE activity and the tetramer structure of BChE.

  6. An evaluation of the inhibition of human butyrylcholinesterase and acetylcholinesterase by the organophosphate chlorpyrifos oxon

    International Nuclear Information System (INIS)

    Shenouda, Josephine; Green, Paula; Sultatos, Lester

    2009-01-01

    Acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8) are enzymes that belong to the superfamily of α/β-hydrolase fold proteins. While they share many characteristics, they also possess many important differences. For example, whereas they have about 54% amino acid sequence identity, the active site gorge of acetylcholinesterase is considerably smaller than that of butyrylcholinesterase. Moreover, both have been shown to display simple and complex kinetic mechanisms, depending on the particular substrate examined, the substrate concentration, and incubation conditions. In the current study, incubation of butyrylthiocholine in a concentration range of 0.005-3.0 mM, with 317 pM human butyrylcholinesterase in vitro, resulted in rates of production of thiocholine that were accurately described by simple Michaelis-Menten kinetics, with a K m of 0.10 mM. Similarly, the inhibition of butyrylcholinesterase in vitro by the organophosphate chlorpyrifos oxon was described by simple Michaelis-Menten kinetics, with a k i of 3048 nM -1 h -1 , and a K D of 2.02 nM. In contrast to inhibition of butyrylcholinesterase, inhibition of human acetylcholinesterase by chlorpyrifos oxon in vitro followed concentration-dependent inhibition kinetics, with the k i increasing as the inhibitor concentration decreased. Chlorpyrifos oxon concentrations of 10 and 0.3 nM gave k i s of 1.2 and 19.3 nM -1 h -1 , respectively. Although the mechanism of concentration-dependent inhibition kinetics is not known, the much smaller, more restrictive active site gorge of acetylcholinesterase almost certainly plays a role. Similarly, the much larger active site gorge of butyrylcholinesterase likely contributes to its much greater reactivity towards chlorpyrifos oxon, compared to acetylcholinesterase.

  7. Retrospective detection of exposure to organophosphorus anti-cholinesterases: Mass spectrometric analysis of phosphylated human butyrylcholinesterase

    NARCIS (Netherlands)

    Fidder, A.; Hulst, A.G.; Noort, D.; Ruiter, R. de; Schans, M.J. van der; Benschop, H.P.; Langenberg, J.P.

    2002-01-01

    In this paper a novel and general procedure is presented for detection of organophosphate-inhibited human butyrylcholinesterase (HuBuChE), which is based on electrospray tandem mass spectrometric analysis of phosphylated nonapeptides obtained after pepsin digestion of the enzyme. The utility of this

  8. Plant-derived human butyrylcholinesterase, but not an organophosphorous-compound hydrolyzing variant thereof, protects rodents against nerve agents

    OpenAIRE

    Geyer, Brian C.; Kannan, Latha; Garnaud, Pierre-Emmanuel; Broomfield, Clarence A.; Cadieux, C. Linn; Cherni, Irene; Hodgins, Sean M.; Kasten, Shane A.; Kelley, Karli; Kilbourne, Jacquelyn; Oliver, Zeke P.; Otto, Tamara C.; Puffenberger, Ian; Reeves, Tony E.; Robbins, Neil

    2010-01-01

    The concept of using cholinesterase bioscavengers for prophylaxis against organophosphorous nerve agents and pesticides has progressed from the bench to clinical trial. However, the supply of the native human proteins is either limited (e.g., plasma-derived butyrylcholinesterase and erythrocytic acetylcholinesterase) or nonexisting (synaptic acetylcholinesterase). Here we identify a unique form of recombinant human butyrylcholinesterase that mimics the native enzyme assembly into tetramers; t...

  9. Synthesis and biological evaluation of lycorine derivatives as dual inhibitors of human acetylcholinesterase and butyrylcholinesterase

    Directory of Open Access Journals (Sweden)

    Wang Yue-Hu

    2012-09-01

    Full Text Available Abstract Background Alzheimer’s disease (AD is a neurologically degenerative disorder that affects more than 20 million people worldwide. The selective butyrylcholinesterase (BChE inhibitors and bivalent cholinesterase (ChE inhibitors represent new treatments for AD. Findings A series of lycorine derivatives (1–10 were synthesized and evaluated for anti-cholinesterase activity. Result showed that the novel compound 2-O-tert-butyldimethylsilyl-1-O-(methylthiomethyllycorine (7 was a dual inhibitor of human acetylcholinesterase (hAChE and butyrylcholinesterase (hBChE with IC50 values of 11.40 ± 0.66 μM and 4.17 ± 0.29 μM, respectively. The structure-activity relationships indicated that (i the 1-O-(methylthiomethyl substituent in lycorine was better than the 1-O-acetyl group for the inhibition of cholinesterase; (ii the acylated or etherified derivatives of lycorine and lycorin-2-one were more potent against hBChE than hAChE; and (iii the oxidation of lycorine at C-2 decreases the activity. Conclusion Acylated or etherified derivatives of lycorine are potential dual inhibitors of hBChE and hAChE. Hence, further study on the modification of lycorine for ChE inhibition is necessary.

  10. In Vitro Ability of Currently Available Oximes to Reactivate Organophosphate Pesticide-Inhibited Human Acetylcholinesterase and Butyrylcholinesterase

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    Kamil Musilek

    2011-03-01

    Full Text Available We have in vitro tested the ability of common, commercially available, cholinesterase reactivators (pralidoxime, obidoxime, methoxime, trimedoxime and HI-6 to reactivate human acetylcholinesterase (AChE, inhibited by five structurally different organophosphate pesticides and inhibitors (paraoxon, dichlorvos, DFP, leptophos-oxon and methamidophos. We also tested reactivation of human butyrylcholinesterase (BChE with the aim of finding a potent oxime, suitable to serve as a “pseudocatalytic” bioscavenger in combination with this enzyme. Such a combination could allow an increase of prophylactic and therapeutic efficacy of the administered enzyme. According to our results, the best broad-spectrum AChE reactivators were trimedoxime and obidoxime in the case of paraoxon, leptophos-oxon, and methamidophos-inhibited AChE. Methamidophos and leptophos-oxon were quite easily reactivatable by all tested reactivators. In the case of methamidophos-inhibited AChE, the lower oxime concentration (10−5 M had higher reactivation ability than the 10−4 M concentration. Therefore, we evaluated the reactivation ability of obidoxime in a concentration range of 10−3–10−7 M. The reactivation of methamidophos-inhibited AChE with different obidoxime concentrations resulted in a bell shaped curve with maximum reactivation at 10−5 M. In the case of BChE, no reactivator exceeded 15% reactivation ability and therefore none of the oximes can be recommended as a candidate for “pseudocatalytic” bioscavengers with BChE.

  11. In Vitro Ability of Currently Available Oximes to Reactivate Organophosphate Pesticide-Inhibited Human Acetylcholinesterase and Butyrylcholinesterase

    OpenAIRE

    Kamil Musilek; Kamil Kuca; Daniel Jun; Lucie Musilova

    2011-01-01

    We have in vitro tested the ability of common, commercially available, cholinesterase reactivators (pralidoxime, obidoxime, methoxime, trimedoxime and HI-6) to reactivate human acetylcholinesterase (AChE), inhibited by five structurally different organophosphate pesticides and inhibitors (paraoxon, dichlorvos, DFP, leptophos-oxon and methamidophos). We also tested reactivation of human butyrylcholinesterase (BChE) with the aim of finding a potent oxime, suitable to serve as a “pseudocatalytic...

  12. Identification of phosphorylated butyrylcholinesterase in human plasma using immunoaffinity purification and mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Aryal, Uma K.; Lin, Chiann Tso; Kim, Jong Seo; Heibeck, Tyler H.; Wang, Jun; Qian, Weijun; Lin, Yuehe

    2012-04-20

    Paraoxon (diethyl 4-nitrophenyl phosphate) is an active metabolite of the common insecticide parathion and is acutely toxic due to the inhibition of cholinesterase (ChE) activity in the nervous systems. The Inhibition of butyrylcholinesterase (BChE) activity by paraoxon is due to the formation of phosphorylated BChE adduct, and the detection of the phosphorylated BChE adduct in human plasma can serve as an exposure biomarker of organophosphate pesticides and nerve agents. In this study, we performed immunoaffinity purification and liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis for identifying phosphorylated BChE in human plasma treated by paraoxon. BChE was captured by biotinylated anti-BChE polyclonal antibodies conjugated to streptavidin magnetic beads. Western blot analysis showed that the antibody was effective to recognize both native and modified BChE with high specificity. The exact phosphorylation site of BChE was confirmed on Serine 198 by MS/MS with a 108 Da modification mass and accurately measured parent ion masses. The phosphorylated BChE peptide was also successfully detected in the immunoaffinity purified sample from paraoxon treated human plasma. Thus, immunoaffinity purification combined with mass spectrometry represents a viable approach for the detection of paraoxon-modified BChE and other forms of modified BChE as exposure biomarkers of organophosphates and nerve agents.

  13. Modeling Evolution of Hydrogen Bonding and Stabilization of Transition States in the Process of Cocaine Hydrolysis Catalyzed by Human Butyrylcholinesterase

    OpenAIRE

    Gao, Daquan; Zhan, Chang-Guo

    2006-01-01

    Molecular dynamics (MD) simulations and quantum mechanical/molecular mechanical (QM/MM) calculations were performed on the prereactive enzyme-substrate complex, transition states, intermediates, and product involved in the process of human butyrylcholinesterase (BChE)-catalyzed hydrolysis of (−)-cocaine. The computational results consistently reveal a unique role of the oxyanion hole (consisting of G116, G117, and A199) in BChE-catalyzed hydrolysis of cocaine, as compared to acetylcholinester...

  14. Calcium-activated butyrylcholinesterase in human skin protects acetylcholinesterase against suicide inhibition by neurotoxic organophosphates

    International Nuclear Information System (INIS)

    Schallreuter, Karin U.; University of Bradford; Elwary, Souna M.; Parkin, Susan M.; Wood, John M.

    2007-01-01

    The human epidermis holds an autocrine acetylcholine production and degradation including functioning membrane integrated and cytosolic butyrylcholinesterase (BuchE). Here we show that BuchE activities increase 9-fold in the presence of calcium (0.5 x 10 -3 M) via a specific EF-hand calcium binding site, whereas acetylcholinesterase (AchE) is not affected. 45 Calcium labelling and computer simulation confirmed the presence of one EF-hand binding site per subunit which is disrupted by H 2 O 2 -mediated oxidation. Moreover, we confirmed the faster hydrolysis by calcium-activated BuchE using the neurotoxic organophosphate O-ethyl-O-(4-nitrophenyl)-phenylphosphonothioate (EPN). Considering the large size of the human skin with 1.8 m 2 surface area with its calcium gradient in the 10 -3 M range, our results implicate calcium-activated BuchE as a major protective mechanism against suicide inhibition of AchE by organophosphates in this non-neuronal tissue

  15. Structure of the gene for human butyrylcholinesterase. Evidence for a single copy

    International Nuclear Information System (INIS)

    Arpagaus, M.; Kott, M.; Vatsis, K.P.; Bartels, C.F.; La Du, B.N.; Lockridge, O.

    1990-01-01

    The authors have isolated five genomic clones for human butyrylcholinesterase (BChE), using cDNA probes encoding the catalytic subunit of the hydrophilic tetramer. The BChE gene is at least 73 kb long and contains for exons. Exon 1 contains untranslated sequences and two potential translation initiation sites at codons -69 and -47. Exon 2 (1525 bp) contains 83% of the coding sequence for the mature protein, including the N-terminal and the active-site serine, and a third possible translation initiation site (likely functional), at codon -28. Exon 3 is 167 nucleotides long. Exon 4 (604 bp) codes for the C-terminus of the protein and the 3' untranslated region where two polyadenylation signals were identified. Intron 1 is 6.5 km long, and the minimal sizes of introns 2 and 3 are estimated to be 32 km each. Southern blot analysis of total human genomic DNA is in complete agreement with the gene structure established by restriction endonuclease mapping of the genomic clones: this strongly suggests that the BChE gene is present in a single copy

  16. A repeated injection of polyethyleneglycol-conjugated recombinant human butyrylcholinesterase elicits immune response in mice

    International Nuclear Information System (INIS)

    Chilukuri, Nageswararao; Sun Wei; Parikh, Kalpana; Naik, Ramachandra S.; Tang Lin; Doctor, Bhupendra P.; Saxena, Ashima

    2008-01-01

    Human serum butyrylcholinesterase (Hu BChE) serves as an efficacious bioscavenger of highly toxic organophosphorus (OP) compounds. Since there is a concern that the supply of native Hu BChE may be limited, monomeric and tetrameric forms of recombinant Hu BChE (rHu BChE) were evaluated as replacements and found that they lacked sufficient stability in vivo. However, their in vivo stability could be significantly prolonged by conjugation with polyethyleneglycol-20K (PEG) suggesting that monomeric and tetrameric PEG-rHu BChE could function as bioscavengers. Here, the immunogenicity of PEG-rHu BChE was evaluated in mice following two injections given four weeks apart. In addition to pharmacokinetic parameters, such as mean residence time, maximal concentration, time to reach the maximal concentration, elimination half-life and area under the plasma concentration-time curve extrapolated to infinity, the presence of circulating anti-rHu BChE antibodies was also determined. Although the pharmacokinetic parameters were significantly improved for the first injection of monomeric and tetrameric PEG-rHu BChEs, they were much lower for the second injection. Anti-rHu BChE antibodies were detected in the blood of mice following the first and second enzyme injections and their levels were approximately higher by 5-fold and 2-fold in mice injected with monomeric and tetrameric PEG-rHu BChEs as compared to mice injected with unconjugated enzymes. The findings that the rapid clearance of a repeat injection of PEG-rHu BChEs in mice which coincides with the presence of circulating anti-rHu BChE antibodies suggest that PEG conjugation prolonged the circulatory stability of rHu BChE but failed to eliminate its immunogenicity in mice

  17. The effect of fluoride on the scavenging of organophosphates by human butyrylcholinesterase in buffer solutions and human plasma

    International Nuclear Information System (INIS)

    Ashani, Yacov; Segev, Omri; Balan, Ayala

    2004-01-01

    Fluoride ion is a reversible inhibitor of human butyrylcholinesterase (HuBChE) that is a viable drug candidate against organophosphates (OPs) toxicity. Since large numbers of communities in many countries are occasionally exposed to relatively high amount of fluoride, its effect on the kinetics of inhibition of HuBChE by OPs was investigated. In saline phosphate, pH 7.4, fluoride in the lower millimolar range significantly slowed the inhibition of HuBChE by paraoxon, DFP, echothiophate, soman, sarin, and VX. The kinetics of the inhibition was found consistent with the formation of a reversible fluoride-HuBChE complex that is at least 25-fold less active towards phosphorylation or phosphonylation than the free enzyme. Heat inactivation experiments indicate that the binding of fluoride to HuBChE probably involves enhanced cross-domain interaction via hydrogen bonds formation that may decrease enzyme activity. In spite of distinct structural differences among the OP used, the dissociation constants of the fluoride-HuBChE reversible complex varied over a narrow range (K F , 0.31-0.70 mM); however, K F in human plasma increased to 2.75-3.40 mM. 19 F-NMR spectroscopy revealed that fluoride ion is complexed to plasma components, an observation that explains in part the apparent increase in K F . Results suggest that an estimate of the relative decrease in the rate of OPs sequestration in presence of fluoride can be obtained from the fraction of the free HuBChE (1 + [F]/K F ) -1 . Considering K F values in human plasma, it is concluded that the scavenging efficacy of OPs by HuBChE is not compromised by the normal concentration range of circulating fluoride ions

  18. Coamplification of human acetylcholinesterase and butyrylcholinesterase genes in blood cells: Correlation with various leukemias and abnormal megakaryocytopoiesis

    International Nuclear Information System (INIS)

    Lapidot-Lifson, Y.; Prody, C.A.; Ginzberg, D.; Meytes, D.; Zakut, H.; Soreq, H.

    1989-01-01

    To study the yet unknown role of the ubiquitous family of cholinesterases (ChoEases) in developing blood cells, the recently isolated cDNAs encoding human acetylcholinesterase and butyrylcholinesterase were used in blot hybridization with peripheral blood DNA from various leukemic patients. Hybridization signals and modified restriction patterns were observed with both cDNA probes in 4 of the 16 leukemia DNA preparations examined. These reflected the amplification of the corresponding AcCho-Ease and BtChoEase genes (ACHE and CHE) and alteration in their structure. Parallel analysis of 30 control samples revealed nonpolymorphic, much weaker hybridization signals for each of the probes. In view of previous reports on the effect of acetylcholine analogs and ChoEase inhibitors in the induction of megakaryocytopoiesis and production of platelets in the mouse. The authors further searched for such phenomena in nonleukemic patients with platelet production disorders. Amplifications of both ACHE and CHE genes were found in 2 of the 4 patients so far examined. Pronounced coamplification of these two related but distinct genes in correlation with pathological production of blood cells suggests a functional role for members of the ChoEase family in megakaryocytopoiesis and raises the question whether the coamplification of these genes could be casually involved in the etiology of hemocytopoietic disorders

  19. Resistance to organophosphorus agent toxicity in transgenic mice expressing the G117H mutant of human butyrylcholinesterase

    International Nuclear Information System (INIS)

    Wang Yuxia; Ticu Boeck, Andreea; Duysen, Ellen G.; Van Keuren, Margaret; Saunders, Thomas L.; Lockridge, Oksana

    2004-01-01

    Organophosphorus toxicants (OP) include chemical nerve agents and pesticides. The goal of this work was to find out whether an animal could be made resistant to OP toxicity by genetic engineering. The human butyrylcholinesterase (BChE) mutant G117H was chosen for study because it has the unusual ability to hydrolyze OP as well as acetylcholine, and it is resistant to inhibition by OP. Human G117H BChE, under the control of the ROSA26 promoter, was expressed in all tissues of transgenic mice. A stable transgenic mouse line expressed 0.5 μg/ml of human G117H BChE in plasma as well as 2 μg/ml of wild-type mouse BChE. Intestine, kidneys, stomach, lungs, heart, spleen, liver, brain, and muscle expressed 0.6-0.15 μg/g of G117H BChE. Transgenic mice were normal in behavior and fertility. The LD50 dose of echothiophate for wild-type mice was 0.1 mg/kg sc. This dose caused severe cholinergic signs of toxicity and lethality in wild-type mice, but caused no deaths and only mild toxicity in transgenic animals. The mechanism of protection was investigated by measuring acetylcholinesterase (AChE) and BChE activity. It was found that AChE and endogenous BChE were inhibited to the same extent in echothiophate-treated wild type and transgenic mice. This led to the hypothesis that protection against echothiophate toxicity was not explained by hydrolysis of echothiophate. In conclusion, the transgenic G117H BChE mouse demonstrates the factors required to achieve protection from OP toxicity in a vertebrate animal

  20. Modeling evolution of hydrogen bonding and stabilization of transition states in the process of cocaine hydrolysis catalyzed by human butyrylcholinesterase.

    Science.gov (United States)

    Gao, Daquan; Zhan, Chang-Guo

    2006-01-01

    Molecular dynamics (MD) simulations and quantum mechanical/molecular mechanical (QM/MM) calculations were performed on the prereactive enzyme-substrate complex, transition states, intermediates, and product involved in the process of human butyrylcholinesterase (BChE)-catalyzed hydrolysis of (-)-cocaine. The computational results consistently reveal a unique role of the oxyanion hole (consisting of G116, G117, and A199) in BChE-catalyzed hydrolysis of cocaine, compared to acetylcholinesterase (AChE)-catalyzed hydrolysis of acetylcholine. During BChE-catalyzed hydrolysis of cocaine, only G117 has a hydrogen bond with the carbonyl oxygen (O31) of the cocaine benzoyl ester in the prereactive BChE-cocaine complex, and the NH groups of G117 and A199 are hydrogen-bonded with O31 of cocaine in all of the transition states and intermediates. Surprisingly, the NH hydrogen of G116 forms an unexpected hydrogen bond with the carboxyl group of E197 side chain and, therefore, is not available to form a hydrogen bond with O31 of cocaine in the acylation. The NH hydrogen of G116 is only partially available to form a weak hydrogen bond with O31 of cocaine in some structures involved in the deacylation. The change of the estimated hydrogen-bonding energy between the oxyanion hole and O31 of cocaine during the reaction process demonstrates how the protein environment can affect the energy barrier for each step of the BChE-catalyzed hydrolysis of cocaine. These insights concerning the effects of the oxyanion hole on the energy barriers provide valuable clues on how to rationally design BChE mutants with a higher catalytic activity for the hydrolysis of (-)-cocaine. 2005 Wiley-Liss, Inc.

  1. Thermostabilisation of human serum butyrylcholinesterase for detection of its inhibitors in water and biological fluids

    Directory of Open Access Journals (Sweden)

    Lakshmanan Jaganathan

    1999-01-01

    Full Text Available The ability of gelatine-trehalose to convert the normally fragile, dry human serum BChE into a thermostable enzyme and its use in the detection of cholinesterase inhibitors in water and biological fluids is described. Gelatine or trehalose alone is unable to protect the dry enzyme against exposure to high temperature, while a combination of gelatine and trehalose were able to protect the enzyme activity against prolonged exposure to temperature as high as +50°C. A method for rapid, simple and inexpensive means of screening for cholinesterase inhibitors such as carbamates and organophosphates in water, vegetables and human blood has been developed.A capacidade da gelatina-trehalose em converter a frágil BChE do soro humano em uma enzima termoestável e seu uso na descoberta de inibidores de colinesterase em água e fluidos biológicos é apresentado. A Gelatina ou trehalose são incapazes de proteger a enzima seca BchE do soro humano contra exposição a elevadas temperaturas, enquanto que uma combinação de gelatina e trehalose são capazes de proteger a atividade de enzima contra exposição prolongada a temperaturas elevadas e da ordem de 50° C. Um método barato, simples e rápido de screening para inibidores de colinesterase tal como carbamatos e organofosfatos em água, verduras e sangue humano foi desenvolvido.

  2. Inhibition kinetics of human serum butyrylcholinesterase by Cd2+, Zn2+ and Al3+: comparison of the effects of metal ions on cholinesterases

    International Nuclear Information System (INIS)

    Sarkarati, B.; Cokugras, A.N.; Tezcan, E.F.

    1999-01-01

    Butyrylcholinesterase (BChE, EC 3.1.1.8) has been purified about 6600-fold from human serum with a procedure including ammonium sulfate fractionation (55-70%) with acid step at pH 4.5 and procainamide-Sepharose 4B affinity chromatography. The purified enzyme exhibited negative cooperativity with respect to butyrylthiocholine (BTCh) binding at pH 7.5. K S was found to be 0.128±0.012 mM. Inhibition kinetics of the enzyme by Cd 2+ , Zn 2+ and Al 3+ were studied in detail. The 1/v vs 1/[BTCh] plots in the absence (control plot) and in the presence of different concentrations of cations intersected above 1/[BTCh]-axis. The data were analyzed by means of a nonlinear curve fitting program. The results demonstrated that all of the three cations are the linear mixed-type inhibitors of BChE. Ca 2+ and Mg 2+ had no effect on the enzyme activity in the experimental conditions. But when the enzyme was inhibited by 0.5 mM Cd 2+ or Zn 2+ , Ca 2+ and Mg 2+ partially reactivated the inhibited allosteric form of BChE. Results were compared with data obtained from brain BChE purified from sheep. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  3. Acetylcholinesterase assay for cerebrospinal fluid using bupivacaine to inhibit butyrylcholinesterase

    Directory of Open Access Journals (Sweden)

    Anders Jens

    2001-12-01

    Full Text Available Abstract Background Most test systems for acetylcholinesterase activity (E.C.3.1.1.7. are using toxic inhibitors (BW284c51 and iso-OMPA to distinguish the enzyme from butyrylcholinesterase (E.C.3.1.1.8. which occurs simultaneously in the cerebrospinal fluid. Applying Ellman's colorimetric method, we were looking for a non-toxic inhibitor to restrain butyrylcholinesterase activity. Based on results of previous in vitro studies bupivacaine emerged to be a suitable inhibitor. Results Pharmacokinetic investigations with purified cholinesterases have shown maximum inhibition of butyrylcholinesterase activity and minimal interference with acetylcholinesterase activity at bupivacaine final concentrations between 0.1 and 0.5 mmol/l. Based on detailed analysis of pharmacokinetic data we developed three equations representing enzyme inhibition at bupivacaine concentrations of 0.1, 0.2 and 0.5 mmol/l. These equations allow us to calculate the acetylcholinesterase activity in solutions containing both cholinesterases utilizing the extinction differences measured spectrophotometrically in samples with and without bupivacaine. The accuracy of the bupivacaine-inhibition test could be confirmed by investigations on solutions of both purified cholinesterases and on samples of human cerebrospinal fluid. If butyrylcholinesterase activity has to be assessed simultaneously an independent test using butyrylthiocholine iodide as substrate (final concentration 5 mmol/l has to be conducted. Conclusions The bupivacaine-inhibition test is a reliable method using spectrophotometrical techniques to measure acetylcholinesterase activity in cerebrospinal fluid. It avoids the use of toxic inhibitors for differentiation of acetylcholinesterase from butyrylcholinesterase in fluids containing both enzymes. Our investigations suggest that bupivacaine concentrations of 0.1, 0.2 or 0.5 mmol/l can be applied with the same effect using 1 mmol/l acetylthiocholine iodide as substrate.

  4. Estudos de QSAR 3D para um conjunto de inibidores de butirilcolinesterase humana QSAR 3D studies of a series of human butyrylcholinesterase inhibitors

    Directory of Open Access Journals (Sweden)

    Humberto F. Freitas

    2009-01-01

    Full Text Available Alzheimer's disease (AD is considered the main cause of cognitive decline in adults. The available therapies for AD treatment seek to maintain the activity of cholinergic system through the inhibition of the enzyme acetylcholinesterase. However, butyrylcholinesterase (BuChE can be considered an alternative target for AD treatment. Aiming at developing new BuChE inhibitors, robust QSAR 3D models with high predictive power were developed. The best model presents a good fit (r²=0.82, q²=0.76, with two PCs and high predictive power (r²predict=0.88. Analysis of regression vector shows that steric properties have considerable importance to the inhibition of the BuChE.

  5. Absorption of orally administered 65Zn by normal human subjects

    International Nuclear Information System (INIS)

    Aamodt, R.L.; Rumble, W.F.; Johnston, G.S.; Markley, E.J.; Henkin, R.I.

    1981-01-01

    Despite studies by several investigators of human gastrointestinal 65Zn absorption, implications of these data for evaluation of functional zinc status are unclear because limited numbers of normal subjects have been studied. To evaluated zinc absorption in normal humans, 75 subjects (31 women, 44 men, ages 18 to 84 yr) were given 10 micro Ci carrier-free 65Zn orally after an overnight fast. Absorption calculated from total body retention measured 7, 14, and 21 days after administration of tracer was 65 +/- 11% (mean +/- 1 SD), range from 40 to 86%. Comparison of these results with those for patients with a variety of diseases indicate that patients exhibit a wider range of absorption and, in four of six studies patients exhibit decreased mean zinc absorption. These results of gastrointestinal zinc absorption in a large number of normal humans offer a basis for a clearer comparison with data from patients who exhibit abnormalities of zinc absorption

  6. Caffeine Inhibits Acetylcholinesterase, But Not Butyrylcholinesterase

    Directory of Open Access Journals (Sweden)

    Petr Dobes

    2013-05-01

    Full Text Available Caffeine is an alkaloid with a stimulant effect in the body. It can interfere in transmissions based on acetylcholine, epinephrine, norepinephrine, serotonin, dopamine and glutamate. Clinical studies indicate that it can be involved in the slowing of Alzheimer disease pathology and some other effects. The effects are not well understood. In the present work, we focused on the question whether caffeine can inhibit acetylcholinesterase (AChE and/or, butyrylcholinesterase (BChE, the two enzymes participating in cholinergic neurotransmission. A standard Ellman test with human AChE and BChE was done for altering concentrations of caffeine. The test was supported by an in silico examination as well. Donepezil and tacrine were used as standards. In compliance with Dixon’s plot, caffeine was proved to be a non-competitive inhibitor of AChE and BChE. However, inhibition of BChE was quite weak, as the inhibition constant, Ki, was 13.9 ± 7.4 mol/L. Inhibition of AChE was more relevant, as Ki was found to be 175 ± 9 µmol/L. The predicted free energy of binding was −6.7 kcal/mol. The proposed binding orientation of caffeine can interact with Trp86, and it can be stabilize by Tyr337 in comparison to the smaller Ala328 in the case of human BChE; thus, it can explain the lower binding affinity of caffeine for BChE with reference to AChE. The biological relevance of the findings is discussed.

  7. Disposal of wastes from radiopharmaceuticals administered in human body in hospital

    International Nuclear Information System (INIS)

    Kaneko, Masao

    1976-01-01

    Radiopharmaceuticals used in hospitals have remarkably increased in amount. Among radioactive matters discharged from pharmaceuticals administered into human bodies, a small amount of radio-pharmaceuticals remained in disporsable containers and syringes, excreta from patients administered such drugs and their washing, may cause the problems, radioisotopes with short half-life such as sup(99m)Tc tend to be administered increasingly while radioisotopes with long life have been decreasing. Long life radioactive wastes and short life wastes have to be strictly separated. And then long life radioisotopes wastes have to be condensed and stored, less than a tenth of the maximum allowable density after decay to discharge. Radioactive gas as 133 Xe should be diffused by ventilation. This is the time to make the numerical guide concerning the problem. (Kobatake, H.)

  8. Pain in adolescent girls receiving human papillomavirus vaccine with concomitantly administered vaccines.

    Science.gov (United States)

    Walter, Emmanuel B; Kemper, Alex R; Dolor, Rowena J; Dunne, Eileen F

    2015-02-01

    Using the Faces Pain Scale - Revised, we assessed injection site pain 10 minutes after vaccination in young females randomized to receive either quadrivalent human papillomavirus vaccine (HPV4) before or after concomitantly administered vaccines. Although pain was modestly more after HPV4 injection than after other vaccines, the pain intensity after HPV4 injection was significantly less in those who received HPV4 before receiving other concomitant vaccines.

  9. Molecular characterization and polymorphisms of butyrylcholinesterase in cynomolgus macaques.

    Science.gov (United States)

    Uno, Yasuhiro; Uehara, Shotaro; Mahadhi, Hassan M D; Ohura, Kayoko; Hosokawa, Masakiyo; Imai, Teruko

    2018-06-01

    Butyrylcholinesterase (BChE), an enzyme essential for drug metabolism, has been investigated as antidotes against organophosphorus nerve agents, and the efficacy and safety have been studied in cynomolgus macaques. BChE polymorphisms partly account for variable BChE activities among individuals in humans, but have not been investigated in cynomolgus macaques. Molecular characterization was carried out by analyzing primary sequence, gene, tissue expression, and genetic variants. In cynomolgus and human BChE, phylogenetically closely related, amino acid residues important for enzyme function were conserved, and gene and genomic structure were similar. Cynomolgus BChE mRNA was most abundantly expressed in liver among the 10 tissue types analyzed. Re-sequencing found 26 non-synonymous genetic variants in 121 cynomolgus and 23 rhesus macaques, indicating that macaque BChE is polymorphic, although none of these variants corresponded to the null or defective alleles of human BChE. These results suggest molecular similarities of cynomolgus and human BChE. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Butyrylcholinesterase activity in Nigerian type 2 diabetics with and ...

    African Journals Online (AJOL)

    USER

    2010-06-28

    Jun 28, 2010 ... Butyrylcholinesterase activity in diabetes and metabolic syndrome is generally under reported. Blood samples and demographic data were obtained from one hundred ... compared with acetyl cholinesterase although it may.

  11. Butyrylcholinesterase activity in Nigerian type 2 diabetics with and ...

    African Journals Online (AJOL)

    USER

    2010-06-28

    Jun 28, 2010 ... Full Length Research Paper. Butyrylcholinesterase ... Type 2 diabetes mellitus is a chronic progressive disease typified by a loss of glycaemic control over time as the ..... susceptibility locus on chromosome position 3q27 but.

  12. Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe.

    Directory of Open Access Journals (Sweden)

    Susanne H Sheehy

    Full Text Available Controlled human malaria infection (CHMI studies have become a routine tool to evaluate efficacy of candidate anti-malarial drugs and vaccines. To date, CHMI trials have mostly been conducted using the bite of infected mosquitoes, restricting the number of trial sites that can perform CHMI studies. Aseptic, cryopreserved P. falciparum sporozoites (PfSPZ Challenge provide a potentially more accurate, reproducible and practical alternative, allowing a known number of sporozoites to be administered simply by injection.We sought to assess the infectivity of PfSPZ Challenge administered in different dosing regimens to malaria-naive healthy adults (n = 18. Six participants received 2,500 sporozoites intradermally (ID, six received 2,500 sporozoites intramuscularly (IM and six received 25,000 sporozoites IM.Five out of six participants receiving 2,500 sporozoites ID, 3/6 participants receiving 2,500 sporozoites IM and 6/6 participants receiving 25,000 sporozoites IM were successfully infected. The median time to diagnosis was 13.2, 17.8 and 12.7 days for 2,500 sporozoites ID, 2,500 sporozoites IM and 25,000 sporozoites IM respectively (Kaplan Meier method; p = 0.024 log rank test.2,500 sporozoites ID and 25,000 sporozoites IM have similar infectivities. Given the dose response in infectivity seen with IM administration, further work should evaluate increasing doses of PfSPZ Challenge IM to identify a dosing regimen that reliably infects 100% of participants.ClinicalTrials.gov NCT01465048.

  13. Focal Electrically Administered Therapy (FEAT): Device parameter effects on stimulus perception in humans

    Science.gov (United States)

    Borckardt, Jeffrey J.; Linder, Katie; Ricci, Raffaella; Li, Xingbao; Anderson, Berry; Arana, Ashley; Nahas, Ziad; Amassian, Vahe; Long, James; George, Mark S.; Sackeim, Harold A.

    2010-01-01

    Background Focal Electrically-Administered Therapy (FEAT) is a new method of transcranial electrical stimulation capable of focal modulation of cerebral activity. Other than invasive studies in animals and examination of motor output in humans, there are limited possibilities for establishing basic principles about how variation in stimulus parameters impact on patterns of intracortical stimulation. This study used a simpler paradigm, and evaluated the effects of different stimulation parameters on subjective perception of the quality and location of scalp pain. Methods In two studies, 19 subjects were randomly stimulated over the left forehead, varying the anode-cathode arrangement, the intensity of stimulation, the electrode size and placement, and whether the current flow was unidirectional or bidirectional. Subjects rated the location of the sensation, and its quality. Results The perceived center of stimulation moved toward the cathode, regardless of placement. This shift in subjective sensation was more prominent when the electricity was unidirectional. Additionally, more intense stimulation, as well as stimulation with a smaller electrode, caused greater perceived pain. Unidirectional stimulation was rated more painful when traveling from a large anode to a small cathode and less painful when traveling from a small anode to a large cathode. Finally, participants were more likely to perceive the electrical stimulation as moving towards a specific direction when the intensity was high than when it was low. Conclusions The intensity and location of sensations can be manipulated by varying the intensity, current direction, or geometry of electrodes. PMID:19092677

  14. Butyrylcholinesterase as a Diagnostic and Therapeutic Target for Alzheimer's Disease.

    Science.gov (United States)

    Darvesh, Sultan

    2016-01-01

    The serine hydrolase butyrylcholinesterase (BChE), like the related enzyme acetylcholinesterase (AChE), co-regulates metabolism of the neurotransmitter acetylcholine. In the human brain BChE is mainly expressed in white matter and glia and in distinct populations of neurons in regions that are important in cognition and behavior, functions compromised in Alzheimer's disease (AD). AD is a neurodegenerative disorder causing dementia with no cure nor means for definitive diagnosis during life. In AD, BChE is found in association with pathology, such as β-amyloid (Aβ) plaques, particularly in the cerebral cortex where BChE is not normally found in quantity. Up to 30% of cognitively normal older adults have abundant Aβ deposition in the brain. We have designed an imaging agent that can detect, through autoradiography, BChE-associated Aβ plaques in the cerebral cortex of AD brains, but does not visualize Aβ plaques in brains of cognitively normal individuals. Furthermore, in an AD mouse model with BChE gene knocked out, there are up to 70% fewer fibrillar Aβ brain plaques, suggesting diminished BChE activity could prove beneficial as a curative approach to AD. To that end, we have examined numerous N-10-carbonyl phenothiazines that are specific inhibitors of human BChE, revealing important details of the enzyme's active site gorge. These phenothiazines can be designed without potential side effects caused by neurotransmitter receptor interactions. In conclusion, BChE is potentially an important target for diagnosis and treatment of AD.

  15. A new detection method for the K variant of butyrylcholinesterase based on PCR primer introduced restriction analysis (PCR-PIRA).

    Science.gov (United States)

    Shibuta, K; Abe, M; Suzuki, T

    1994-01-01

    The K variant of human butyrylcholinesterase is caused by a G/A transition in the butyrylcholinesterase gene, which neither creates nor destroys any restriction site. In an attempt to detect the K variant both simply and rapidly, we developed a two step method of "PCR primer introduced restriction analysis" (PCR-PIRA). The first step was used to introduce a new Fun4HI site into the normal allele for a screening test, while the second step was performed to create a new MaeIII site on the variant allele for a specific test. This method thus enabled us to distinguish clearly the K variant from the normal allele, and also showed that the frequency of the K variant allele is 0.164 in the Japanese population. Images PMID:7966197

  16. Authority of Pharmacists to Administer Human Papillomavirus Vaccine: Alignment of State Laws With Age-Level Recommendations.

    Science.gov (United States)

    Dingman, Deirdre A; Schmit, Cason D

    One strategy to increase the uptake of human papillomavirus (HPV) vaccine among adolescents is through the use of pharmacists. Our objectives were to (1) use a publicly available database to describe the statutory and regulatory authority of pharmacists to administer the HPV vaccine in the United States and (2) discuss how the current status of laws may influence achievement of the Healthy People 2020 goal of 80% HPV vaccination rate for teenagers aged 13-15. Using information from the Centers for Disease Control and Prevention's (CDC's) Public Health Law Program database, we identified state laws in effect as of January 1, 2016, giving pharmacists authority to administer vaccines. We used a standardized analysis algorithm to determine whether states' laws (1) authorized pharmacists to administer HPV vaccine, (2) required third-party authorization for pharmacist administration, and (3) restricted HPV vaccine administration by pharmacists to certain patient age groups. Of 50 states and the District of Columbia, 40 had laws expressly granting pharmacists authority to administer HPV vaccine to patients, but only 22 had laws that authorized pharmacists to vaccinate preadolescents aged 11 or 12 (ie, the CDC-recommended age group). Pharmacists were granted prescriptive authority by 5 states, and they were given authority pursuant to general (non-patient-specific) third-party authorization (eg, a licensed health care provider) by 32 states or patient-specific third-party authorization by 3 states. Most states permitted pharmacists to administer HPV vaccines only to boys and girls older than 11 or 12, which may hinder achievement of the Healthy People 2020 goal for HPV vaccination. Efforts should be made to strengthen the role of pharmacists in addressing this public health issue.

  17. Consolidation and reconsolidation are impaired by oral propranolol administered before but not after memory (re)activation in humans.

    Science.gov (United States)

    Thomas, Émilie; Saumier, Daniel; Pitman, Roger K; Tremblay, Jacques; Brunet, Alain

    2017-07-01

    Propranolol administered immediately after learning or after recall has been found to impair memory consolidation or reconsolidation (respectively) in animals, but less reliably so in humans. Since reconsolidation impairment has been proposed as a treatment for mental disorders that have at their core an emotional memory, it is desirable to understand how to reliably reduce the strength of pathogenic memories in humans. We postulated that since humans (unlike experimental animals) typically receive propranolol orally, this introduces a delay before this drug can exert its memory impairment effects, which may render it less effective. As a means to test this, in two double-blind placebo-controlled experiments, we examined the capacity of propranolol to impair consolidation and reconsolidation as a function of timing of ingestion in healthy subjects. In Experiment 1, (n=36), propranolol administered immediately after learning or recall failed to impair the consolidation or reconsolidation of the memory of a standardized slideshow with an accompanying emotional story. In Experiment 2 (n=50), propranolol given 60-75min before learning or recall successfully impaired memory consolidation and reconsolidation. These results suggest that it is possible to achieve reliable memory impairment in humans if propranolol is given before learning or before recall, but not after. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Cocrystallization studies of full-length recombinant butyrylcholinesterase (BChE) with cocaine

    Energy Technology Data Exchange (ETDEWEB)

    Asojo, Oluwatoyin Ajibola; Asojo, Oluyomi Adebola; Ngamelue, Michelle N.; Homma, Kohei; Lockridge, Oksana (Nebraska-Med)

    2011-09-16

    Human butyrylcholinesterase (BChE; EC 3.1.1.8) is a 340 kDa tetrameric glycoprotein that is present in human serum at about 5 mg l{sup -1} and has well documented therapeutic effects on cocaine toxicity. BChE holds promise as a therapeutic that reduces and finally eliminates the rewarding effects of cocaine, thus weaning an addict from the drug. There have been extensive computational studies of cocaine hydrolysis by BChE. Since there are no reported structures of BChE with cocaine or any of the hydrolysis products, full-length monomeric recombinant wild-type BChE was cocrystallized with cocaine. The refined 3 {angstrom} resolution structure appears to retain the hydrolysis product benzoic acid in sufficient proximity to form a hydrogen bond to the active-site Ser198.

  19. The Fate of ZnO Nanoparticles Administered to Human Bronchial Epithelial Cells

    Science.gov (United States)

    Gilbert, Benjamin; Fakra, Sirine C.; Xia, Tian; Pokhrel, Suman; Mädler, Lutz; Nel, André E.

    2014-01-01

    A particular challenge for nanotoxicology is the evaluation of the biological fate and toxicity of nanomaterials that dissolve in aqueous fluids. Zinc oxide nanomaterials are of particular concern because dissolution leads to release of the toxic divalent zinc ion. Although dissolved zinc ions have been implicated in ZnO cytotoxicity, direct identification of the chemical form of zinc taken up by cells exposed to ZnO nanoparticles, and its intracellular fate, has not yet been achieved. We combined high resolution X-ray spectromicroscopy and high elemental sensitivity X-ray microprobe analyses to determine the fate of ZnO and less soluble iron-doped ZnO nanoparticles following exposure to cultures of human bronchial epithelial cells, BEAS-2B. We complemented two-dimensional X-ray imaging methods with atomic force microscopy of cell surfaces to distinguish between nanoparticles that were transported inside the cells from those that adhered to the cell exterior. The data suggest cellular uptake of ZnO nanoparticles is a mechanism of zinc accumulation in cells. Following uptake, ZnO nanoparticles dissolved completely generating intracellular Zn2+ complexed by molecular ligands. These results corroborate a model for ZnO nanoparticle toxicity that is based on nanoparticle uptake followed by intracellular dissolution. PMID:22646753

  20. The evaluation of lyophilized polymer matrices for administering recombinant human bone morphogenetic protein-2.

    Science.gov (United States)

    Duggirala, S S; Rodgers, J B; DeLuca, P P

    1996-07-01

    Novel unitary devices, prepared by lyophilization of viscous solutions of sodium carboxymethylcellulose (CMC) and methylcellulose (MC), were evaluated as sustained-release delivery systems for recombinant human bone morphogenetic protein-2 (rhBMP-2). In vitro characterization of the unitary devices, which contained rhBMP-2-loaded poly (d,l lactide-co-glycolide) (PLGA) bioerodible particles (BEPs), was conducted over a 2-month period. Determinations included buffer uptake, mass and molecular weight loss and rhBMP-2 release from the unitary devices. CMC devices imbibed approximately 16 times their weight of buffer, while with MC, equilibrium uptake was approximately 6 times the dry weight of the devices. Overall mass loss percentages were approximately 55 and 35%, respectively, for CMC and MC devices. rhBMP-2 release from the devices was essentially a triphasic process: an initial phase during which "free" protein (rhBMP-2 present on the surface and within the pores of the PLGA BEPs) was released, a lag period during which no release was discerned, and then release of "bound" rhBMP-2 (protein adsorbed to the BEPs). The release of bound protein correlated with the mass loss of the polymer which began after 3 weeks. Release from the unitary devices was lower than that from the BEPs alone, due to a retardation effect of the gelled CMC/MC polymers. In rabbits in which full-thickness cranial bone defects were created, the implants were well tolerated and induced significant new bone growth during an 8-week evaluation period. The CMC devices appear to have induced bone earlier (at 2 weeks), but this did not affect eventual 8-week results. CMC devices without rhBMP-2 appeared to provide some bone conduction, in contrast to the blank MC devices.

  1. A comprehensive evaluation of novel oximes in creation of butyrylcholinesterase-based nerve agent bioscavengers

    International Nuclear Information System (INIS)

    Katalinić, Maja; Maček Hrvat, Nikolina; Baumann, Krešimir; Morasi Piperčić, Sara; Makarić, Sandro; Tomić, Srđanka; Jović, Ozren; Hrenar, Tomica; Miličević, Ante; Jelić, Dubravko; Žunec, Suzana; Primožič, Ines; Kovarik, Zrinka

    2016-01-01

    A well-considered treatment of acute nerve agents poisoning involves the exogenous administration of butyrylcholinesterase (BChE, EC 3.1.1.8) as a stoichiometric bioscavenger efficient in preventing cholinergic crises caused by acetylcholinesterase (AChE, EC 3.1.1.7) inhibition. An additional improvement in medical countermeasures would be to use oximes that could reactivate BChE as well to upgrade bioscavenging from stoichiometric to oxime-assisted catalytic. Therefore, in this paper we investigated the potency of 39 imidazolium and benzimidazolium oximes (36 compounds synthesized for the first time) to be considered as the reactivators specifically designed for reactivation of phosphylated human BChE. Their efficiency in the reactivation of paraoxon-, VX-, and tabun-inhibited human BChE, as well as human AChE was tested and compared with the efficiencies of HI-6 and obidoxime, used in medical practice today. A comprehensive analysis was performed for the most promising oximes defining kinetic parameters of reactivation as well as interactions with uninhibited BChE. Furthermore, experimental data were compared with computational studies (docking, QSAR analysis) as a starting point in future oxime structure refinement. Considering the strict criteria set for in vivo applications, we determined the cytotoxicity of lead oximes on two cell lines. Among the tested oxime library, one imidazolium compound was selected for preliminary in vivo antidotal study in mice. The obtained protection in VX poisoning outlines its potential in development oxime-assisted OP-bioscavenging with BChE. - Highlights: • 36 new imidazolium and benzimidazolium oximes were designed and synthesized. • In vitro reactivation kinetics of phosphylated butyrylcholinesterase was studded. • The modes of actions were elucidated by QSAR and docking simulations. • Protection in VX poisoning was 6.3 × LD 50 in in vivo antidotal study in mice. • Imidazolium oxime-assisted catalysis is feasible

  2. A comprehensive evaluation of novel oximes in creation of butyrylcholinesterase-based nerve agent bioscavengers

    Energy Technology Data Exchange (ETDEWEB)

    Katalinić, Maja; Maček Hrvat, Nikolina [Institute for Medical Research and Occupational Health, POB 291, HR-10001 Zagreb (Croatia); Baumann, Krešimir; Morasi Piperčić, Sara; Makarić, Sandro; Tomić, Srđanka; Jović, Ozren; Hrenar, Tomica [Department of Chemistry, Faculty of Science, University of Zagreb, HR-10001 Zagreb (Croatia); Miličević, Ante [Institute for Medical Research and Occupational Health, POB 291, HR-10001 Zagreb (Croatia); Jelić, Dubravko [Fidelta Ltd., HR-10001 Zagreb (Croatia); Žunec, Suzana [Institute for Medical Research and Occupational Health, POB 291, HR-10001 Zagreb (Croatia); Primožič, Ines, E-mail: ines.primozic@chem.pmf.hr [Department of Chemistry, Faculty of Science, University of Zagreb, HR-10001 Zagreb (Croatia); Kovarik, Zrinka, E-mail: zkovarik@imi.hr [Institute for Medical Research and Occupational Health, POB 291, HR-10001 Zagreb (Croatia)

    2016-11-01

    A well-considered treatment of acute nerve agents poisoning involves the exogenous administration of butyrylcholinesterase (BChE, EC 3.1.1.8) as a stoichiometric bioscavenger efficient in preventing cholinergic crises caused by acetylcholinesterase (AChE, EC 3.1.1.7) inhibition. An additional improvement in medical countermeasures would be to use oximes that could reactivate BChE as well to upgrade bioscavenging from stoichiometric to oxime-assisted catalytic. Therefore, in this paper we investigated the potency of 39 imidazolium and benzimidazolium oximes (36 compounds synthesized for the first time) to be considered as the reactivators specifically designed for reactivation of phosphylated human BChE. Their efficiency in the reactivation of paraoxon-, VX-, and tabun-inhibited human BChE, as well as human AChE was tested and compared with the efficiencies of HI-6 and obidoxime, used in medical practice today. A comprehensive analysis was performed for the most promising oximes defining kinetic parameters of reactivation as well as interactions with uninhibited BChE. Furthermore, experimental data were compared with computational studies (docking, QSAR analysis) as a starting point in future oxime structure refinement. Considering the strict criteria set for in vivo applications, we determined the cytotoxicity of lead oximes on two cell lines. Among the tested oxime library, one imidazolium compound was selected for preliminary in vivo antidotal study in mice. The obtained protection in VX poisoning outlines its potential in development oxime-assisted OP-bioscavenging with BChE. - Highlights: • 36 new imidazolium and benzimidazolium oximes were designed and synthesized. • In vitro reactivation kinetics of phosphylated butyrylcholinesterase was studded. • The modes of actions were elucidated by QSAR and docking simulations. • Protection in VX poisoning was 6.3 × LD{sub 50} in in vivo antidotal study in mice. • Imidazolium oxime-assisted catalysis is

  3. Butyrylcholinesterase, lipoxygenase inhibiting and antifungal alkaloids from Isatis tinctoria.

    Science.gov (United States)

    Ahmad, Ijaz; Fatima, Itrat

    2008-06-01

    Phytochemical investigations on the alkaloidal fraction of the whole plant of the Isatis tinctoria led to the isolation of the alkaloids 1-6. Compounds 3, 2 were found to be potent butyrylcholinesterase and lipoxygenase enzymes inhibitors in a concentration-dependent manner with the IC(50) values 16.3 +/- 0.06 and 19.7 +/- 0.03 microM against BChE and 30.6 +/- 0.02 and 33.7 +/- 0.05 microM against LOX, respectively. The compounds (1-6) showed significant antifungal activity against Trichophyton schoen leinii, Aspergillus niger, Candida albicans, Trichophyton simii, and Macrophomina phaseolina.

  4. Identification of C5+ extraband of butyrylcholinesterase and two protein bands cathodic to it

    OpenAIRE

    F. D. Suyatna; R. Setiabudy; O. Tjandra; E. Herwana

    2001-01-01

    Electrophoresis of human plasma yields 4 butyrylcholinesterase (BChE) protein bands, i.e. C1, C2, C3, C4 and in some individuals also an extraband C5+. In addition to that other protein bands called "S" bands are also invariably detected. In order to know whether the C5+ and the "S" bands are related to the BChE protein, we have carried out immunological and peptide mapping studies on these proteins. The immunology approach was done by raising polyclonal antibodies against each protein bands ...

  5. Functional variability in butyrylcholinesterase activity regulates intrathecal cytokine and astroglial biomarker profiles in patients with Alzheimer's disease

    DEFF Research Database (Denmark)

    Darreh-Shori, Taher; Vijayaraghavan, Swetha; Aeinehband, Shahin

    2013-01-01

    Butyrylcholinesterase (BuChE) activity is associated with activated astrocytes in Alzheimer's disease brain. The BuChE-K variant exhibits 30%-60% reduced acetylcholine (ACh) hydrolyzing capacity. Considering the increasing evidence of an immune-regulatory role of ACh, we investigated if genetic...... findings, such as high cerebral glucose utilization, low β-amyloid load, and less severe progression of clinical symptoms. In vitro analysis on human astrocytes confirmed the involvement of a regulated BuChE status in the astroglial responses to TNF-α and ACh. Histochemical analysis in a rat model of nerve...

  6. Human kinetics of orally and intravenously administered low-dose 1,2-(13)C-dichloroacetate.

    Science.gov (United States)

    Jia, Minghong; Coats, Bonnie; Chadha, Monisha; Frentzen, Barbara; Perez-Rodriguez, Javier; Chadik, Paul A; Yost, Richard A; Henderson, George N; Stacpoole, Peter W

    2006-12-01

    Dichloroacetate (DCA) is a putative environmental hazard, owing to its ubiquitous presence in the biosphere and its association with animal and human toxicity. We sought to determine the kinetics of environmentally relevant concentrations of 1,2-(13)C-DCA administered to healthy adults. Subjects received an oral or intravenous dose of 2.5 microg/kg of 1,2-(13)C-DCA. Plasma and urine concentrations of 1,2-(13)C-DCA were measured by a modified gas chromatography-tandem mass spectrometry method. 1,2-(13)C-DCA kinetics was determined by modeling using WinNonlin 4.1 software. Plasma concentrations of 1,2-(13)C-DCA peaked 10 minutes and 30 minutes after intravenous or oral administration, respectively. Plasma kinetic parameters varied as a function of dose and duration. Very little unchanged 1,2-(13)C-DCA was excreted in urine. Trace amounts of DCA alter its own kinetics after short-term exposure. These findings have important implications for interpreting the impact of this xenobiotic on human health.

  7. Blood-Brain Barrier Opening in Behaving Non-Human Primates via Focused Ultrasound with Systemically Administered Microbubbles

    Science.gov (United States)

    Downs, Matthew E.; Buch, Amanda; Karakatsani, Maria Eleni; Konofagou, Elisa E.; Ferrera, Vincent P.

    2015-10-01

    Over the past fifteen years, focused ultrasound coupled with intravenously administered microbubbles (FUS) has been proven an effective, non-invasive technique to open the blood-brain barrier (BBB) in vivo. Here we show that FUS can safely and effectively open the BBB at the basal ganglia and thalamus in alert non-human primates (NHP) while they perform a behavioral task. The BBB was successfully opened in 89% of cases at the targeted brain regions of alert NHP with an average volume of opening 28% larger than prior anesthetized FUS procedures. Safety (lack of edema or microhemorrhage) of FUS was also improved during alert compared to anesthetized procedures. No physiological effects (change in heart rate, motor evoked potentials) were observed during any of the procedures. Furthermore, the application of FUS did not disrupt reaching behavior, but in fact improved performance by decreasing reaction times by 23 ms, and significantly decreasing touch error by 0.76 mm on average.

  8. Butyrylcholinesterase gene mutations in patients with prolonged apnea after succinylcholine for electroconvulsive therapy

    DEFF Research Database (Denmark)

    Mollerup, Hannah Malthe; Gätke, M R

    2011-01-01

    patients undergoing electroconvulsive therapy (ECT) often receive succinylcholine as part of the anesthetic procedure. The duration of action may be prolonged in patients with genetic variants of the butyrylcholinesterase enzyme (BChE), the most common being the K- and the A-variants. The aim...... of the study was to assess the clinical significance of genetic variants in butyrylcholinesterase gene (BCHE) in patients with a suspected prolonged duration of action of succinylcholine after ECT....

  9. Genetic variants of serum butyrylcholinesterase in Chilean Mapuche Indians.

    Science.gov (United States)

    Acuña, M; Eaton, L; Ramírez, N R; Cifuentes, L; Llop, E

    2003-05-01

    We estimated the frequencies of serum butyrylcholinesterase (BChE) alleles in three tribes of Mapuche Indians from southern Chile, using enzymatic methods, and we estimated the frequency of allele BCHE*K in one tribe using primer reduced restriction analysis (PCR-PIRA). The three tribes have different degrees of European admixture, which is reflected in the observed frequencies of the atypical allele BCHE*A: 1.11% in Huilliches, 0.89% in Cuncos, and 0% in Pehuenches. This result is evidence in favor of the hypothesis that BCHE*A is absent in native Amerindians. The frequencies of BCHE*F were higher than in most reported studies (3.89%, 5.78%, and 4.41%, respectively). These results are probably due to an overestimation of the frequency of allele BCHE*F, since none of the 20 BCHE UF individuals (by the enzymatic test) individuals analyzed showed either of the two DNA base substitutions associated with this allele. Although enzymatic methods rarely detect the presence of allele BCHE*K, PCR-PIRA found the allele in an appreciable frequency (5.76%), although lower than that found in other ethnic groups. Since observed frequencies of unusual alleles correspond to estimated percentages of European admixture, it is likely that none of these unusual alleles were present in Mapuche Indians before the arrival of Europeans. Copyright 2003 Wiley-Liss, Inc.

  10. Synthesis and biological evaluation of phloroglucinol derivatives possessing α-glycosidase, acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase inhibitory activity.

    Science.gov (United States)

    Burmaoglu, Serdar; Yilmaz, Ali O; Taslimi, Parham; Algul, Oztekin; Kilic, Deryanur; Gulcin, Ilhami

    2018-02-01

    A series of novel phloroglucinol derivatives were designed, synthesized, characterized spectroscopically and tested for their inhibitory activity against selected metabolic enzymes, including α-glycosidase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human carbonic anhydrase I and II (hCA I and II). These compounds displayed nanomolar inhibition levels and showed K i values of 1.14-3.92 nM against AChE, 0.24-1.64 nM against BChE, 6.73-51.10 nM against α-glycosidase, 1.80-5.10 nM against hCA I, and 1.14-5.45 nM against hCA II. © 2018 Deutsche Pharmazeutische Gesellschaft.

  11. Application of Savitzky-Golay differentiation filters and Fourier functions to simultaneous determination of cefepime and the co-administered drug, levofloxacin, in spiked human plasma

    Science.gov (United States)

    Abdel-Aziz, Omar; Abdel-Ghany, Maha F.; Nagi, Reham; Abdel-Fattah, Laila

    2015-03-01

    The present work is concerned with simultaneous determination of cefepime (CEF) and the co-administered drug, levofloxacin (LEV), in spiked human plasma by applying a new approach, Savitzky-Golay differentiation filters, and combined trigonometric Fourier functions to their ratio spectra. The different parameters associated with the calculation of Savitzky-Golay and Fourier coefficients were optimized. The proposed methods were validated and applied for determination of the two drugs in laboratory prepared mixtures and spiked human plasma. The results were statistically compared with reported HPLC methods and were found accurate and precise.

  12. Application of Savitzky-Golay differentiation filters and Fourier functions to simultaneous determination of cefepime and the co-administered drug, levofloxacin, in spiked human plasma.

    Science.gov (United States)

    Abdel-Aziz, Omar; Abdel-Ghany, Maha F; Nagi, Reham; Abdel-Fattah, Laila

    2015-03-15

    The present work is concerned with simultaneous determination of cefepime (CEF) and the co-administered drug, levofloxacin (LEV), in spiked human plasma by applying a new approach, Savitzky-Golay differentiation filters, and combined trigonometric Fourier functions to their ratio spectra. The different parameters associated with the calculation of Savitzky-Golay and Fourier coefficients were optimized. The proposed methods were validated and applied for determination of the two drugs in laboratory prepared mixtures and spiked human plasma. The results were statistically compared with reported HPLC methods and were found accurate and precise. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. New Insights into Butyrylcholinesterase Activity Assay: Serum Dilution Factor as a Crucial Parameter.

    Directory of Open Access Journals (Sweden)

    Joanna Jońca

    Full Text Available Butyrylcholinesterase (BChE activity assay and inhibitor phenotyping can help to identify patients at risk of prolonged paralysis following the administration of neuromuscular blocking agents. The assay plays an important role in clinical chemistry as a good diagnostic marker for intoxication with pesticides and nerve agents. Furthermore, the assay is also commonly used for in vitro characterization of cholinesterases, their toxins and drugs. There is still lack of standardized procedure for measurement of BChE activity and many laboratories use different substrates at various concentrations. The purpose of this study was to validate the BChE activity assay to determine the best dilution of human serum and the most optimal concentration of substrates and inhibitors. Serum BChE activity was measured using modified Ellman's method applicable for a microplate reader. We present our experience and new insights into the protocol for high-throughput routine assays of human plasma cholinesterase activities adapted to a microplate reader. During our routine assays used for the determination of BChE activity, we have observed that serum dilution factor influences the results obtained. We show that a 400-fold dilution of serum and 5mM S-butyrylthiocholine iodide can be successfully used for the accurate measurement of BChE activity in human serum. We also discuss usage of various concentrations of dibucaine and fluoride in BChE phenotyping. This study indicates that some factors of such a multicomponent clinical material like serum can influence kinetic parameters of the BChE. The observed inhibitory effect is dependent on serum dilution factor used in the assay.

  14. Freezing and thawing effects on fat, protein, and lactose levels of human natural milk administered by gavage and continuous infusion

    Directory of Open Access Journals (Sweden)

    Andrea D. Abranches

    2014-07-01

    Full Text Available OBJECTIVES: to analyze the changes in human milk macronutrients: fat, protein, and lactose in natural human milk (raw, frozen and thawed, after administration simulation by gavage and continuous infusion. METHOD: an experimental study was performed with 34 human milk samples. The infrared spectrophotometry using the infrared analysis equipment MilkoScan Minor(r (Foss, Denmark equipment was used to analyze the macronutrients in human milk during the study phases. The analyses were performed in natural (raw samples and after freezing and fast thawing following two steps: gavage and continuous infusion. The non-parametric Wilcoxon test for paired samples was used for the statistical analysis. RESULTS: the fat content was significantly reduced after administration by continuous infusion (p < 0.001 during administration of both raw and thawed samples. No changes in protein and lactose content were observed between the two forms of infusion. However, the thawing process significantly increased the levels of lactose and milk protein. CONCLUSION: the route of administration by continuous infusion showed the greatest influence on fat loss among all the processes required for human milk administration.

  15. Freezing and thawing effects on fat, protein, and lactose levels of human natural milk administered by gavage and continuous infusion.

    Science.gov (United States)

    Abranches, Andrea D; Soares, Fernanda V M; Junior, Saint-Clair G; Moreira, Maria Elisabeth L

    2014-01-01

    to analyze the changes in human milk macronutrients: fat, protein, and lactose in natural human milk (raw), frozen and thawed, after administration simulation by gavage and continuous infusion. an experimental study was performed with 34 human milk samples. The infrared spectrophotometry using the infrared analysis equipment MilkoScan Minor® (Foss, Denmark) equipment was used to analyze the macronutrients in human milk during the study phases. The analyses were performed in natural (raw) samples and after freezing and fast thawing following two steps: gavage and continuous infusion. The non-parametric Wilcoxon test for paired samples was used for the statistical analysis. the fat content was significantly reduced after administration by continuous infusion (praw and thawed samples. No changes in protein and lactose content were observed between the two forms of infusion. However, the thawing process significantly increased the levels of lactose and milk protein. the route of administration by continuous infusion showed the greatest influence on fat loss among all the processes required for human milk administration. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  16. Enabling Healthcare IT Governance: Human Task Management Service for Administering Emergency Department's Resources for Efficient Patient Flow.

    Science.gov (United States)

    Rodriguez, Salvador; Aziz, Ayesha; Chatwin, Chris

    2014-01-01

    The use of Health Information Technology (HIT) to improve healthcare service delivery is constantly increasing due to research advances in medical science and information systems. Having a fully automated process solution for a Healthcare Organization (HCO) requires a combination of organizational strategies along with a selection of technologies that facilitate the goal of improving clinical outcomes. HCOs, requires dynamic management of care capability to realize the full potential of HIT. Business Process Management (BPM) is being increasingly adopted to streamline the healthcare service delivery and management processes. Emergency Departments (EDs) provide a case in point, which require multidisciplinary resources and services to deliver effective clinical outcomes. Managed care involves the coordination of a range of services in an ED. Although fully automated processes in emergency care provide a cutting edge example of service delivery, there are many situations that require human interactions with the computerized systems; e.g. Medication Approvals, care transfer, acute patient care. This requires a coordination mechanism for all the resources, computer and human, to work side by side to provide the best care. To ensure evidence-based medical practice in ED, we have designed a Human Task Management service to model the process of coordination of ED resources based on the UK's NICE Clinical guideline for managing the care of acutely ill patients. This functionality is implemented using Java Business process Management (jBPM).

  17. Butyrylcholinesterase gene mutations in patients with prolonged apnea after succinylcholine for electroconvulsive therapy

    DEFF Research Database (Denmark)

    Mollerup, Hannah Malthe; Gätke, M R

    2011-01-01

    patients undergoing electroconvulsive therapy (ECT) often receive succinylcholine as part of the anesthetic procedure. The duration of action may be prolonged in patients with genetic variants of the butyrylcholinesterase enzyme (BChE), the most common being the K- and the A-variants. The aim...

  18. Attenuated Human Parainfluenza Virus Type 1 Expressing Ebola Virus Glycoprotein GP Administered Intranasally Is Immunogenic in African Green Monkeys.

    Science.gov (United States)

    Lingemann, Matthias; Liu, Xueqiao; Surman, Sonja; Liang, Bo; Herbert, Richard; Hackenberg, Ashley D; Buchholz, Ursula J; Collins, Peter L; Munir, Shirin

    2017-05-15

    The recent 2014-2016 Ebola virus (EBOV) outbreak prompted increased efforts to develop vaccines against EBOV disease. We describe the development and preclinical evaluation of an attenuated recombinant human parainfluenza virus type 1 (rHPIV1) expressing the membrane-anchored form of EBOV glycoprotein GP, as an intranasal (i.n.) EBOV vaccine. GP was codon optimized and expressed either as a full-length protein or as an engineered chimeric form in which its transmembrane and cytoplasmic tail (TMCT) domains were replaced with those of the HPIV1 F protein in an effort to enhance packaging into the vector particle and immunogenicity. GP was inserted either preceding the N gene (pre-N) or between the N and P genes (N-P) of rHPIV1 bearing a stabilized attenuating mutation in the P/C gene (C Δ170 ). The constructs grew to high titers and efficiently and stably expressed GP. Viruses were attenuated, replicating at low titers over several days, in the respiratory tract of African green monkeys (AGMs). Two doses of candidates expressing GP from the pre-N position elicited higher GP neutralizing serum antibody titers than the N-P viruses, and unmodified GP induced higher levels than its TMCT counterpart. Unmodified EBOV GP was packaged into the HPIV1 particle, and the TMCT modification did not increase packaging or immunogenicity but rather reduced the stability of GP expression during in vivo replication. In conclusion, we identified an attenuated and immunogenic i.n. vaccine candidate expressing GP from the pre-N position. It is expected to be well tolerated in humans and is available for clinical evaluation. IMPORTANCE EBOV hemorrhagic fever is one of the most lethal viral infections and lacks a licensed vaccine. Contact of fluids from infected individuals, including droplets or aerosols, with mucosal surfaces is an important route of EBOV spread during a natural outbreak, and aerosols also might be exploited for intentional virus spread. Therefore, vaccines that protect

  19. Hupresin Retains Binding Capacity for Butyrylcholinesterase and Acetylcholinesterase after Sanitation with Sodium Hydroxide

    Directory of Open Access Journals (Sweden)

    Seda Onder

    2017-10-01

    Full Text Available Hupresin is a new affinity resin that binds butyrylcholinesterase (BChE in human plasma and acetylcholinesterase (AChE solubilized from red blood cells (RBC. Hupresin is available from the CHEMFORASE company. BChE in human plasma binds to Hupresin and is released with 0.1 M trimethylammonium bromide (TMA with full activity and 10–15% purity. BChE immunopurified from plasma by binding to immobilized monoclonal beads has fewer contaminating proteins than the one-step Hupresin-purified BChE. However, when affinity chromatography on Hupresin follows ion exchange chromatography at pH 4.5, BChE is 99% pure. The membrane bound AChE, solubilized from human RBC with 0.6% Triton X-100, binds to Hupresin and remains bound during washing with sodium chloride. Human AChE is not released in significant quantities with non-denaturing solvents, but is recovered in 1% trifluoroacetic acid. The denatured, partially purified AChE is useful for detecting exposure to nerve agents by mass spectrometry. Our goal was to determine whether Hupresin retains binding capacity for BChE and AChE after Hupresin is washed with 0.1 M NaOH. A 2 mL column of Hupresin equilibrated in 20 mM TrisCl pH 7.5 was used in seven consecutive trials to measure binding and recovery of BChE from 100 mL human plasma. Between each trial the Hupresin was washed with 10 column volumes of 0.1 M sodium hydroxide. A similar trial was conducted with red blood cell AChE in 0.6% Triton X-100. It was found that the binding capacity for BChE and AChE was unaffected by washing Hupresin with 0.1 M sodium hydroxide. Hupresin could be washed with sodium hydroxide at least seven times without losing binding capacity.

  20. Dosimetry of intravenously administered oxygen-15 labelled water in man: a model based on experimental human data from 21 subjects

    International Nuclear Information System (INIS)

    Smith, T.; Tong, C.; Lammertsma, A.A.; Butler, K.R.; Schnorr, L.; Watson, J.D.G.; Ramsay, S.; Clark, J.C.; Jones, T.

    1994-01-01

    Models based on uniform distribution of tracer in total body water underestimate the absorbed dose from H 2 15 O because of the short half-life (2.04 min) of 15 O, which leads to non-uniform distribution of absorbed dose and also complicates the direct measurement of organ retention curves. However, organ absorbed doses can be predicted by the present kinetic model based on the convolution technique. The measured time course of arterial H 2 15 O concentration following intravenous administration represents the input function to organs. The impulse response of a given organ is its transit time function determined by blood flow and the partition of water between tissue and blood. Values of these two parameters were taken from the literature. Integrals of the arterial input function and organ transit time functions were used to derive integrals of organ retention functions (organ residence times). The latter were used with absorbed dose calculation software (MIRDOSE-2) to obtain estimates for 24 organs. From the mean values of organ absorbed doses, the effective dose equivalent (EDE) and effective dose (ED) were calculated. From measurements on 21 subjects, the average value for both EDE and ED was calculated to be 1.2 μSv.MBq -1 compared with a value of about 0.5 μSv.MBq -1 predicted by uniform water distribution models. Based on the human data, a method of approximating H 2 15 O absorbed dose values from body surface area is described. (orig.)

  1. Patients with prolonged effect of succinylcholine or mivacurium had novel mutations in the butyrylcholinesterase gene

    DEFF Research Database (Denmark)

    Wichmann, Sine; Færk, Gitte; Bundgaard, Jens R.

    2016-01-01

    with prolonged duration of action to succinylcholine and mivacurium. Patients were studied if they had equivocal phenotypes on the basis of BChE activity, biochemical inhibitor reactions and with pedigree if possible. Complete nucleotide sequencing was performed to describe the genotype and pedigree was used......Introduction Mutations in the butyrylcholinesterase enzyme (BChE) can result in prolonged duration of action of the neuromuscular blocking agents, succinylcholine and mivacurium, as BChE hydrolyses these drugs. Hereditary low BChE activity can cause extensively prolonged apnoea during general...... anaesthesia when these drugs are used. The aim of this study was to describe novel mutations in the butyrylcholinesterase gene (BCHE) in patients who have experienced prolonged duration of action of mivacurium or succinylcholine. Methods The Danish Cholinesterase Research Unit registers patients...

  2. 22 CFR 196.4 - Administering office.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Administering office. 196.4 Section 196.4... AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.4 Administering office. The Department of State's Bureau of Human Resources, Office of Recruitment is responsible for administering the Thomas R...

  3. Synthesis, Biological Evaluation, and Docking Studies of Novel Bisquaternary Aldoxime Reactivators on Acetylcholinesterase and Butyrylcholinesterase Inhibited by Paraoxon

    Directory of Open Access Journals (Sweden)

    Kamil Kuca

    2018-05-01

    Full Text Available Nerve agents and oxon forms of organophosphorus pesticides act as strong irreversible inhibitors of two cholinesterases in the human body: acetylcholinesterase (AChE; EC 3.1.1.7 and butyrylcholinesterase (BChE; EC 3.1.1.8, and are therefore highly toxic compounds. For the recovery of inhibited AChE, antidotes from the group of pyridinium or bispyridinium aldoxime reactivators (pralidoxime, obidoxime, HI-6 are used in combination with anticholinergics and anticonvulsives. Therapeutic efficacy of reactivators (called “oximes” depends on their chemical structure and also the type of organophosphorus inhibitor. Three novel oximes (K131, K142, K153 with an oxime group in position four of the pyridinium ring were designed and then tested for their potency to reactivate human (Homo sapiens sapiens AChE (HssACHE and BChE (HssBChE inhibited by the pesticide paraoxon (diethyl 4-nitrophenyl phosphate. According to the obtained results, none of the prepared oximes were able to satisfactorily reactivate paraoxon-inhibited cholinesterases. On the contrary, extraordinary activity of obidoxime in the case of paraoxon-inhibited HssAChE reactivation was confirmed. Additional docking studies pointed to possible explanations for these results.

  4. The effects of orally administered Beta-glucan on innate immune responses in humans, a randomized open-label intervention pilot-study.

    Directory of Open Access Journals (Sweden)

    Jenneke Leentjens

    Full Text Available To prevent or combat infection, increasing the effectiveness of the immune response is highly desirable, especially in case of compromised immune system function. However, immunostimulatory therapies are scarce, expensive, and often have unwanted side-effects. β-glucans have been shown to exert immunostimulatory effects in vitro and in vivo in experimental animal models. Oral β-glucan is inexpensive and well-tolerated, and therefore may represent a promising immunostimulatory compound for human use.We performed a randomized open-label intervention pilot-study in 15 healthy male volunteers. Subjects were randomized to either the β -glucan (n = 10 or the control group (n = 5. Subjects in the β-glucan group ingested β-glucan 1000 mg once daily for 7 days. Blood was sampled at various time-points to determine β-glucan serum levels, perform ex vivo stimulation of leukocytes, and analyze microbicidal activity.β-glucan was barely detectable in serum of volunteers at all time-points. Furthermore, neither cytokine production nor microbicidal activity of leukocytes were affected by orally administered β-glucan.The present study does not support the use of oral β-glucan to enhance innate immune responses in humans.ClinicalTrials.gov NCT01727895.

  5. Attitudes and factors affecting acceptability of self-administered cervicovaginal sampling for human papillomavirus (HPV) genotyping as an alternative to Pap testing among multiethnic Malaysian women

    Science.gov (United States)

    Ma'som, Mahirah; Bhoo-Pathy, Nirmala; Nasir, Nazrila Hairizan; Bellinson, Jerome; Subramaniam, Shridevi; Ma, Yuntong; Yap, Siew-Hwei; Goh, Pik-Pin; Gravitt, Patti; Woo, Yin Ling

    2016-01-01

    Objective The objective of this study was to determine the attitudes and acceptability of self-administered cervicovaginal sampling compared with conventional physician-acquired Papanicolaou (Pap) smear among multiethnic Malaysian women. Method A cross-sectional study was carried out via interviewer-administered surveys from August 2013 through August 2015 at five government-run, urban health clinics in the state of Selangor. Subjects were participants from an ongoing community-based human papillomavirus (HPV) prevalence study who answered a standard questionnaire before and after self-sampling. The cervicovaginal self-sampling for HPV genotyping was performed using a simple brush (‘Just for Me’; Preventive Oncology International, Hong Kong). Detailed data on sociodemographics, previous Pap smear experience, and attitudes towards self-administered cervicovaginal sampling were collected and analysed. Acceptability was inferred using a five-item Likert scale that included six different subjective descriptives: experience, difficulty, convenience, embarrassment, discomfort or pain, and confidence in collecting one's own sample. Results Of the 839 participants, 47.9% were Malays, followed by 30.8% Indians, 18.8% Chinese and 2.5% from other ethnicities. The median age of the participants was 38 years (IQR 30–48). Some 68.2% of participants indicated a preference for self-sampling over the Pap test, with 95% indicating willingness to follow-up a positive result at the hospital. Age, ethnicity and previous Pap test experience were significant independent factors associated with preference for self-sampling. The older the individual, the less likely they were to prefer self-sampling (adjusted OR 0.94, 95% CI 0.90 to 0.98). The Chinese were less likely to prefer self-sampling (72.6%) than the Malays (85.1%) (adjusted OR 0.57, 95% CI 0.33 to 0.98, p=0.004). Participants who had never undergone a Pap smear were also more likely to prefer self-sampling (88.5%) than

  6. The interactions of azure B, a metabolite of methylene blue, with acetylcholinesterase and butyrylcholinesterase

    International Nuclear Information System (INIS)

    Petzer, Anél; Harvey, Brian H.; Petzer, Jacobus P.

    2014-01-01

    Methylene blue (MB) is reported to possess diverse pharmacological actions and is attracting increasing attention for the treatment of neurodegenerative disorders such as Alzheimer's disease. Among the pharmacological actions of MB, is the significant inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These activities may, at least in part, underlie MB's beneficial effects in Alzheimer's disease. MB is metabolized to yield N-demethylated products of which azure B, the monodemethyl metabolite, is the predominant species. Azure B has been shown to be pharmacologically active and also possesses a variety of biological actions. Azure B therefore may contribute to the pharmacological profile of MB. Based on these considerations, the present study investigates the possibility that azure B may, similar to MB, act as an inhibitor of human AChE and BuChE. The results document that azure B inhibits AChE and BuChE with IC 50 values of 0.486 μM and 1.99 μM, respectively. The results further show that azure B inhibits AChE and BuChE reversibly, and that the modes of inhibition are most likely competitive. Although the AChE and BuChE inhibitory activities of azure B are twofold and fivefold, respectively, less potent than those recorded for MB [IC 50 (AChE) = 0.214 μM; IC 50 (BuChE) = 0.389 μM] under identical conditions, azure B may be a contributor to MB's in vivo activation of the cholinergic system and beneficial effects in Alzheimer's disease. - Highlights: • Methylene blue (MB) is a known inhibitor of AChE and BuChE. • Azure B, the major metabolite of MB, also is an inhibitor of AChE and BuChE. • Azure B may be a contributor to MB's in vivo activation of the cholinergic system. • Azure B may contribute to MB's potential in Alzheimer's disease therapy

  7. Human chorionic gonadotropin-administered natural cycle versus spontaneous ovulatory cycle in patients undergoing two pronuclear zygote frozen-thawed embryo transfer.

    Science.gov (United States)

    Lee, You-Jung; Kim, Chung-Hoon; Kim, Do-Young; Ahn, Jun-Woo; Kim, Sung-Hoon; Chae, Hee-Dong; Kang, Byung-Moon

    2018-03-01

    To compare human chorionic gonadotropin (HCG)-administered natural cycle with spontaneous ovulatory cycle in patients undergoing frozen-thawed embryo transfer (FTET) in natural cycles. In this retrospective cohort study, we analyzed the clinical outcome of a total of 166 consecutive FTET cycles that were performed in either natural cycle controlled by HCG for ovulation triggering (HCG group, n=110) or natural cycle with spontaneous ovulation (control group, n=56) in 166 infertile patients between January 2009 and November 2013. There were no differences in patients' characteristics between the 2 groups. The numbers of oocytes retrieved, mature oocytes, fertilized oocytes, grade I or II embryos and frozen embryos in the previous in vitro fertilization (IVF) cycle in which embryos were frozen were comparable between the HCG and control groups. Significant differences were not also observed between the 2 groups in clinical pregnancy rate (CPR), embryo implantation rate, miscarriage rate, live birth rate and multiple CPR. However, the number of hospital visits for follicular monitoring was significantly fewer in the HCG group than in the control group ( P cycle reduces the number of hospital visits for follicular monitoring without any detrimental effect on FTET outcome when compared with spontaneous ovulatory cycles in infertile patients undergoing FTET in natural ovulatory cycles.

  8. The Ramazzini Institute 13-week pilot study on glyphosate and Roundup administered at human-equivalent dose to Sprague Dawley rats: effects on the microbiome.

    Science.gov (United States)

    Mao, Qixing; Manservisi, Fabiana; Panzacchi, Simona; Mandrioli, Daniele; Menghetti, Ilaria; Vornoli, Andrea; Bua, Luciano; Falcioni, Laura; Lesseur, Corina; Chen, Jia; Belpoggi, Fiorella; Hu, Jianzhong

    2018-05-29

    Glyphosate-based herbicides (GBHs) are broad-spectrum herbicides that act on the shikimate pathway in bacteria, fungi, and plants. The possible effects of GBHs on human health are the subject of an intense public debate for both its potential carcinogenic and non-carcinogenic effects, including its effects on microbiome. The present pilot study examines whether exposure to GBHs at doses of glyphosate considered to be "safe" (the US Acceptable Daily Intake - ADI - of 1.75 mg/kg bw/day), starting from in utero, may modify the composition of gut microbiome in Sprague Dawley (SD) rats. Glyphosate alone and Roundup, a commercial brand of GBHs, were administered in drinking water at doses comparable to the US glyphosate ADI (1.75 mg/kg bw/day) to F0 dams starting from the gestational day (GD) 6 up to postnatal day (PND) 125. Animal feces were collected at multiple time points from both F0 dams and F1 pups. The gut microbiota of 433 fecal samples were profiled at V3-V4 region of 16S ribosomal RNA gene and further taxonomically assigned and assessed for diversity analysis. We tested the effect of exposure on overall microbiome diversity using PERMANOVA and on individual taxa by LEfSe analysis. Microbiome profiling revealed that low-dose exposure to Roundup and glyphosate resulted in significant and distinctive changes in overall bacterial composition in F1 pups only. Specifically, at PND31, corresponding to pre-pubertal age in humans, relative abundance for Bacteriodetes (Prevotella) was increased while the Firmicutes (Lactobacillus) was reduced in both Roundup and glyphosate exposed F1 pups compared to controls. This study provides initial evidence that exposures to commonly used GBHs, at doses considered safe, are capable of modifying the gut microbiota in early development, particularly before the onset of puberty. These findings warrant future studies on potential health effects of GBHs in early development such as childhood.

  9. A phase I randomized clinical trial of candidate human immunodeficiency virus type 1 vaccine MVA.HIVA administered to Gambian infants.

    Directory of Open Access Journals (Sweden)

    Muhammed O Afolabi

    Full Text Available A vaccine to decrease transmission of human immunodeficiency virus type 1 (HIV-1 during breast-feeding would complement efforts to eliminate infant HIV-1 infection by antiretroviral therapy. Relative to adults, infants have distinct immune development, potentially high-risk of transmission when exposed to HIV-1 and rapid progression to AIDS when infected. To date, there have been only three published HIV-1 vaccine trials in infants.We conducted a randomized phase I clinical trial PedVacc 001 assessing the feasibility, safety and immunogenicity of a single dose of candidate vaccine MVA.HIVA administered intramuscularly to 20-week-old infants born to HIV-1-negative mothers in The Gambia.Infants were followed to 9 months of age with assessment of safety, immunogenicity and interference with Expanded Program on Immunization (EPI vaccines. The trial is the first stage of developing more complex prime-boost vaccination strategies against breast milk transmission of HIV-1.From March to October 2010, 48 infants (24 vaccine and 24 no-treatment were enrolled with 100% retention. The MVA.HIVA vaccine was safe with no difference in adverse events between vaccinees and untreated infants. Two vaccine recipients (9% and no controls had positive ex vivo interferon-γ ELISPOT assay responses. Antibody levels elicited to the EPI vaccines, which included diphtheria, tetanus, whole-cell pertussis, hepatitis B virus, Haemophilus influenzae type b and oral poliovirus, reached protective levels for the vast majority and were similar between the two arms.A single low-dose of MVA.HIVA administered to 20-week-old infants in The Gambia was found to be safe and without interference with the induction of protective antibody levels by EPI vaccines, but did not alone induce sufficient HIV-1-specific responses. These data support the use of MVA carrying other transgenes as a boosting vector within more complex prime-boost vaccine strategies against transmission of HIV-1 and

  10. Association between butyrylcholinesterase K variant and mild cognitive impairment in the Thai community-dwelling patients

    Directory of Open Access Journals (Sweden)

    Pongthanaracht N

    2017-05-01

    Full Text Available Natsalil Pongthanaracht,1 Somchai Yanarojana,1 Darawan Pinthong,1 Supeenun Unchern,1 Amnuay Thithapandha,1 Prasert Assantachai,2 Porntip Supavilai11Department of Pharmacology, Faculty of Science, 2Department of Preventive and Social Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandObjective: To study the association of the butyrylcholinesterase K variant (BChE-K and the plasma BChE activity with mild cognitive impairment (MCI in Thai community-dwelling patients.Methods: One hundred patients diagnosed with MCI and 100 control subjects were recruited from the community-dwelling setting in Bangkok, Thailand. The genotype and allele distributions of the BChE-K were determined by polymerase chain reaction and subsequent DNA sequencing. The BChE activity was measured in plasma according to the Ellman’s method.Results: The BChE-K allele frequencies in the Thai community-dwelling patients were in accordance with other ethnics. The BChE-K allele frequency in the control subjects (12% was higher than that of MCI patients (5.5%, suggesting a protective role of BChE-K for MCI in the Thai community-dwelling patients. The BChE-K homozygotes were significantly associated with lower BChE activity.Conclusion: Our results suggested that the BChE-K may be implicated as a protective factor for MCI in the Thai community-dwelling patients, although a further study with a large sample size is warranted to confirm this.Keywords: butyrylcholinesterase K variant, butyrylcholinesterase activity, mild cognitive impairment, Thai community-dwelling patients

  11. Cervical Cancer Screening Preferences Among Trans-Masculine Individuals: Patient-Collected Human Papillomavirus Vaginal Swabs Versus Provider-Administered Pap Tests.

    Science.gov (United States)

    McDowell, Michal; Pardee, Dana J; Peitzmeier, Sarah; Reisner, Sari L; Agénor, Madina; Alizaga, Natalie; Bernstein, Ida; Potter, Jennifer

    2017-08-01

    Trans-masculine (TM, i.e., persons who have a masculine spectrum gender identity, but were assigned female sex at birth) individuals face disparities in cervical cancer screening rates compared to cisgender women. Some unique barriers to screening in this population are specific to Pap tests. Introduction of self-collected frontal (i.e., vaginal) swabs for human papillomavirus (HPV) testing as a screening strategy may obviate these barriers. This study elucidates cervical cancer screening preferences among TM individuals. TM individuals participated in in-depth interviews (n = 31) and online surveys (n = 32) to explore perceptions and experiences regarding cervical cancer screening, including the acceptability of self-collected frontal HPV swabs for cervical cancer screening compared to provider-administered Pap tests. Provider-collected frontal HPV swab acceptability was also explored. Most TM individuals (94% in-person and 91% online participants) preferred either the self- or provider-collected frontal HPV swab to the Pap test. Participants perceived self- and provider-collected frontal HPV swabs to be less invasive, provoke less gender discordance, and promote a greater sense of agency compared to Pap tests. However, some participants expressed concern about HPV swab accuracy and, regarding the self-collected swab, discomfort about the need to engage with genitals they may not want to acknowledge. Individuals who reported positive provider relationships found Pap tests and provider-collected frontal swabs more acceptable than those who did not. Frontal HPV swabs have the potential to promote regular cervical cancer screening among TM individuals and to narrow screening disparities. Work is ongoing to establish swab accuracy and develop shared decision-making tools.

  12. Township Administered Roads

    Data.gov (United States)

    Minnesota Department of Natural Resources — This data set contains roadway centerlines for township administered roads found on the USGS 1:24,000 mapping series. In some areas, these roadways are current...

  13. Effect of viologen-phosphorus dendrimers on acetylcholinesterase and butyrylcholinesterase activities.

    Science.gov (United States)

    Ciepluch, Karol; Weber, Monika; Katir, Nadia; Caminade, Anne-Marie; El Kadib, Abdelkrim; Klajnert, Barbara; Majoral, Jean Pierre; Bryszewska, Maria

    2013-03-01

    The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is the first step in checking whether new compounds can be considered as drugs for treating neurodegenerative diseases. The effect of viologen-phosphorus dendrimers on AChE and BChE activities was studied. The results show that the effects on the cholinesterase activities depend on dendrimer type and size. Viologen dendrimers can interact with the enzymes in two ways: they can bind either to a peripheral site of the enzyme or to amino acids located near the active site, inhibiting catalysis by both cholinesterases. All tested non-toxic viologen-phosphorus dendrimers inhibited the activities of both cholinesterases, showing their potential as new drugs for treating neurodegenerative diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Synthesis of some new 3-coumaranone and coumarin derivatives as dual inhibitors of acetyl- and butyrylcholinesterase.

    Science.gov (United States)

    Alipour, Masoumeh; Khoobi, Mehdi; Nadri, Hamid; Sakhteman, Amirhossein; Moradi, Alireza; Ghandi, Mehdi; Foroumadi, Alireza; Shafiee, Abbas

    2013-08-01

    A novel series of coumarin and 3-coumaranone derivatives encompassing the phenacyl pyridinium moiety were synthesized and evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity using Ellman's method. All compounds presented inhibitory activity against both AChE and BuChE in the micromolar range. The molecular docking simulations revealed that all compounds were dual binding site inhibitors of AChE. A kinetic study was performed and the mechanism of enzyme inhibition was proved to be of mixed type. All compounds were tested for their antioxidant activity and no significant activity was observed. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Butyrylcholinesterase Levels on Admission Predict Severity and 12-Month Mortality in Hospitalized AIDS Patients

    Science.gov (United States)

    Xu, Lijun; Huang, Ying; Yang, Zongxing; Sun, Jia; Xu, Yan; Zheng, Jinlei; Kinloch, Sabine; Yin, Michael T.; Weng, Honglei

    2018-01-01

    Background Butyrylcholinesterase (BChE) is synthesized mainly in the liver and an important marker in many infectious/inflammatory diseases, but its role in acquired immunodeficiency syndrome (AIDS) patients is not clear. We wished to ascertain if BChE level is associated with the progression/prognosis of AIDS patients. Methods BChE levels (in U/L) were measured in 505 patients; assessed. Kaplan–Meier curves and Cox proportional hazards model were used to assess associations between low BChE levels and mortality, after adjustment for age, CD4 count, WHO stage, and laboratory parameters. Results A total of 129 patients (25.5%) had a lower BChE level. BChE was closely associated with CD4 count, WHO stage, CRP level, and BMI (all P AIDS severity and is an independent risk factor for increased mortality in AIDS patients. PMID:29736152

  16. 1,500 IU human chorionic gonadotropin administered at oocyte retrieval rescues the luteal phase when gonadotropin-releasing hormone agonist is used for ovulation induction

    DEFF Research Database (Denmark)

    Humaidan, Peter; Bredkjær, Helle Ejdrup; Westergaard, Lars Grabow

    2009-01-01

    OBJECTIVE: To prospectively assess the reproductive outcome with a small bolus of hCG administered on the day of oocyte retrieval after ovulation induction with a GnRH agonist (GnRHa). DESIGN: Prospective, randomized trial. SETTING: Three hospital-based IVF clinics. PATIENT(S): Three hundred five...... IVF/intracytoplasmic sperm injection patients after a GnRH antagonist protocol. INTERVENTION(S): Ovulation induction was performed with either 10,000 IU hCG or 0.5 mg GnRHa (buserelin) supplemented with 1,500 IU hCG on the day of oocyte retrieval. MAIN OUTCOME MEASURE(S): Reproductive outcome...... bolus of hCG in the GnRHa group secured the luteal phase, resulting in a comparable reproductive outcome in the two groups. However, a nonsignificant difference of 7% in delivery rates justifies further studies to refine the use of GnRHa for ovulation induction....

  17. Plant-expressed cocaine hydrolase variants of butyrylcholinesterase exhibit altered allosteric effects of cholinesterase activity and increased inhibitor sensitivity

    OpenAIRE

    Larrimore, Katherine E.; Kazan, I. Can; Kannan, Latha; Kendle, R. Player; Jamal, Tameem; Barcus, Matthew; Bolia, Ashini; Brimijoin, Stephen; Zhan, Chang-Guo; Ozkan, S. Banu; Mor, Tsafrir S.

    2017-01-01

    Butyrylcholinesterase (BChE) is an enzyme with broad substrate and ligand specificities and may function as a generalized bioscavenger by binding and/or hydrolyzing various xenobiotic agents and toxicants, many of which target the central and peripheral nervous systems. Variants of BChE were rationally designed to increase the enzyme?s ability to hydrolyze the psychoactive enantiomer of cocaine. These variants were cloned, and then expressed using the magnICON transient expression system in p...

  18. Safety, pharmacokinetics, and pharmacodynamics of TV-1380, a novel mutated butyrylcholinesterase treatment for cocaine addiction, after single and multiple intramuscular injections in healthy subjects.

    Science.gov (United States)

    Cohen-Barak, Orit; Wildeman, Jacqueline; van de Wetering, Jeroen; Hettinga, Judith; Schuilenga-Hut, Petra; Gross, Aviva; Clark, Shane; Bassan, Merav; Gilgun-Sherki, Yossi; Mendzelevski, Boaz; Spiegelstein, Ofer

    2015-05-01

    Human plasma butyrylcholinesterase (BChE) contributes to cocaine metabolism and has been considered for use in treating cocaine addiction and cocaine overdose. TV-1380 is a recombinant protein composed of the mature form of human serum albumin fused at its amino terminus to the carboxy-terminus of a truncated and mutated BChE. In preclinical studies, TV-1380 has been shown to rapidly eliminate cocaine in the plasma thus forestalling entry of cocaine into the brain and heart. Two randomized, blinded phase I studies were conducted to evaluate the safety, pharmacokinetics, and pharmacodynamics of TV-1380, following single and multiple administration in healthy subjects. TV-1380 was found to be safe and well tolerated with a long half-life (43-77 hours) and showed a dose-proportional increase in systemic exposure. Consistent with preclinical results, the ex vivo cocaine hydrolysis, TV-1380 activity clearly increased upon treatment in a dose-dependent manner. In addition, there was a direct relationship between ex vivo cocaine hydrolysis (kel ) and TV-1380 serum concentrations. There was no evidence that TV-1380 affected heart rate, the uncorrected QT interval, or the heart-rate-corrected QTcF interval. TV-1380, therefore, offers a safe once-weekly therapy to increase cocaine hydrolysis. © 2015 The Authors. The Journal of Clinical Pharmacology Published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  19. Synthesis and discovery of potent carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase, and α-glycosidase enzymes inhibitors: The novel N,N'-bis-cyanomethylamine and alkoxymethylamine derivatives.

    Science.gov (United States)

    Taslimi, Parham; Caglayan, Cuneyt; Farzaliyev, Vagif; Nabiyev, Oruj; Sujayev, Afsun; Turkan, Fikret; Kaya, Ruya; Gulçin, İlhami

    2018-04-01

    During this investigation, N,N'-bis-azidomethylamines, N,N'-bis-cyanomethylamine, new alkoxymethylamine and chiral derivatives, which are considered to be a new generation of multifunctional compounds, were synthesized, functional properties were investigated, and anticholinergic and antidiabetic properties of those compounds were studied through the laboratory tests, and it was approved that they contain physiologically active compounds rather than analogues. Novel N-bis-cyanomethylamine and alkoxymethylamine derivatives were effective inhibitors of the α-glycosidase, cytosolic carbonic anhydrase I and II isoforms, butyrylcholinesterase (BChE), and acetylcholinesterase (AChE) with K i values in the range of 0.15-13.31 nM for α-glycosidase, 2.77-15.30 nM for human carbonic anhydrase isoenzymes I (hCA I), 3.12-21.90 nM for human carbonic anhydrase isoenzymes II (hCA II), 23.33-73.23 nM for AChE, and 3.84-48.41 nM for BChE, respectively. Indeed, the inhibition of these metabolic enzymes has been considered as a promising factor for pharmacologic intervention in a diversity of disturbances. © 2018 Wiley Periodicals, Inc.

  20. GM-CSF increases mucosal and systemic immunogenicity of an H1N1 influenza DNA vaccine administered into the epidermis of non-human primates.

    Directory of Open Access Journals (Sweden)

    Peter T Loudon

    2010-06-01

    Full Text Available The recent H5N1 avian and H1N1 swine-origin influenza virus outbreaks reaffirm that the threat of a world-wide influenza pandemic is both real and ever-present. Vaccination is still considered the best strategy for protection against influenza virus infection but a significant challenge is to identify new vaccine approaches that offer accelerated production, broader protection against drifted and shifted strains, and the capacity to elicit anti-viral immune responses in the respiratory tract at the site of viral entry. As a safe alternative to live attenuated vaccines, the mucosal and systemic immunogenicity of an H1N1 influenza (A/New Caledonia/20/99 HA DNA vaccine administered by particle-mediated epidermal delivery (PMED or gene gun was analyzed in rhesus macaques.Macaques were immunized at weeks 0, 8, and 16 using a disposable single-shot particle-mediated delivery device designed for clinical use that delivers plasmid DNA directly into cells of the epidermis. Significant levels of hemagglutination inhibiting (HI antibodies and cytokine-secreting HA-specific T cells were observed in the periphery of macaques following 1-3 doses of the PMED HA DNA vaccine. In addition, HA DNA vaccination induced detectable levels of HA-specific mucosal antibodies and T cells in the lung and gut-associated lymphoid tissues of vaccinated macaques. Importantly, co-delivery of a DNA encoding the rhesus macaque GM-CSF gene was found to significantly enhance both the systemic and mucosal immunogenicity of the HA DNA vaccine.These results provide strong support for the development of a particle-mediated epidermal DNA vaccine for protection against respiratory pathogens such as influenza and demonstrate, for the first time, the ability of skin-delivered GM-CSF to serve as an effective mucosal adjuvant for vaccine induction of immune responses in the gut and respiratory tract.

  1. Acetylcholinesterase and butyrylcholinesterase inhibitory activity of Pinus species essential oils and their constituents.

    Science.gov (United States)

    Bonesi, Marco; Menichini, Federica; Tundis, Rosa; Loizzo, Monica R; Conforti, Filomena; Passalacqua, Nicodemo G; Statti, Giancarlo A; Menichini, Francesco

    2010-10-01

    This study aimed to investigate the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity of the essential oils from Pinus nigra subsp. nigra, P. nigra var. calabrica, and P. heldreichii subsp. leucodermis. This activity is relevant to the treatment of Alzheimer's disease (AD), since cholinesterase drugs are currently the only drugs available to treat AD. P. heldreichii subsp. leucodermis exhibited the most promising activity, with IC(50) values of 51.1 and 80.6 microg/mL against AChE and BChE, respectively. An interesting activity against AChE was also observed with P. nigra subsp. nigra essential oil, with an IC(50) value of 94.4 microg/mL. Essential oils were analyzed by GC and GC-MS with the purpose of investigating their relationships with the observed activities. Among the identified constituents, terpinolene, beta-phellandrene, linalyl acetate, trans-caryophyllene, and terpinen-4-ol were tested. trans-Caryophyllene and terpinen-4-ol inhibited BChE with IC(50) values of 78.6 and 107.6 microg/mL, respectively. beta-Phellandrene was selective against AChE (IC(50) value of 120.2 microg/mL).

  2. New Cinchona Oximes Evaluated as Reactivators of Acetylcholinesterase and Butyrylcholinesterase Inhibited by Organophosphorus Compounds

    Directory of Open Access Journals (Sweden)

    Maja Katalinić

    2017-07-01

    Full Text Available For the last six decades, researchers have been focused on finding efficient reactivators of organophosphorus compound (OP-inhibited acetylcholinesterase (AChE and butyrylcholinesterase (BChE. In this study, we have focused our research on a new oxime scaffold based on the Cinchona structure since it was proven to fit the cholinesterases active site and reversibly inhibit their activity. Three Cinchona oximes (C1, C2, and C3, derivatives of the 9-oxocinchonidine, were synthesized and investigated in reactivation of various OP-inhibited AChE and BChE. As the results showed, the tested oximes were more efficient in the reactivation of BChE and they reactivated enzyme activity to up to 70% with reactivation rates similar to known pyridinium oximes used as antidotes in medical practice today. Furthermore, the oximes showed selectivity towards binding to the BChE active site and the determined enzyme-oxime dissociation constants supported work on the future development of inhibitors in other targeted studies (e.g., in treatment of neurodegenerative disease. Also, we monitored the cytotoxic effect of Cinchona oximes on two cell lines Hep G2 and SH-SY5Y to determine the possible limits for in vivo application. The cytotoxicity results support future studies of these compounds as long as their biological activity is targeted in the lower micromolar range.

  3. Novel 2-pheynlbenzofuran derivatives as selective butyrylcholinesterase inhibitors for Alzheimer's disease.

    Science.gov (United States)

    Kumar, Amit; Pintus, Francesca; Di Petrillo, Amalia; Medda, Rosaria; Caria, Paola; Matos, Maria João; Viña, Dolores; Pieroni, Enrico; Delogu, Francesco; Era, Benedetta; Delogu, Giovanna L; Fais, Antonella

    2018-03-13

    Alzheimer's disease (AD) is a neurodegenerative disorder representing the leading cause of dementia and is affecting nearly 44 million people worldwide. AD is characterized by a progressive decline in acetylcholine levels in the cholinergic systems, which results in severe memory loss and cognitive impairments. Expression levels and activity of butyrylcholinesterase (BChE) enzyme has been noted to increase significantly in the late stages of AD, thus making it a viable drug target. A series of hydroxylated 2-phenylbenzofurans compounds were designed, synthesized and their inhibitory activities toward acetylcholinesterase (AChE) and BChE enzymes were evaluated. Two compounds (15 and 17) displayed higher inhibitory activity towards BChE with IC 50 values of 6.23 μM and 3.57 μM, and a good antioxidant activity with EC 50 values 14.9 μM and 16.7 μM, respectively. The same compounds further exhibited selective inhibitory activity against BChE over AChE. Computational studies were used to compare protein-binding pockets and evaluate the interaction fingerprints of the compound. Molecular simulations showed a conserved protein residue interaction network between the compounds, resulting in similar interaction energy values. Thus, combination of biochemical and computational approaches could represent rational guidelines for further structural modification of these hydroxy-benzofuran derivatives as future drugs for treatment of AD.

  4. Structural and functional analysis of glycoprotein butyrylcholinesterase using atomistic molecular dynamics

    Science.gov (United States)

    Bernardi, Austen; Faller, Roland

    Atomistic molecular dynamics (MD) has proven to be a powerful tool for studying the structure and dynamics of biological systems on nanosecond to microsecond time scales and nanometer length scales. In this work we study the effects of modifying the glycan distribution on the structure and function of full length monomeric butyrylcholinesterase (BChE). BChE exists as a monomer, dimer, or tetramer, and is a therapeutic glycoprotein with nine asparagine glycosylation sites per monomer. Each monomer acts as a stoichiometric scavenger for organophosphorus (OP) nerve agents (e.g. sarin, soman). Glycan distributions are highly heterogeneous and have been shown experimentally to affect certain glycoproteins' stability and reactivity. We performed structural analysis of various biologically relevant glycoforms of BChE using classical atomistic MD. Functional analysis was performed through binding energy simulations using umbrella sampling with BChE and OP cofactors. Additionally, we assess the quality of the glycans' conformational sampling. We found that the glycan distribution has a significant effect on the structure and function of BChE on timescales available to atomistic MD. This project is funded by the DTRA Grant HDTRA1-15-1-0054.

  5. New anthrarobin acyl derivatives as butyrylcholinesterase inhibitors: synthesis, in vitro and in silico studies

    Directory of Open Access Journals (Sweden)

    Mehreen Lateef

    2017-07-01

    Full Text Available To treat Alzheimer's disease (AD, the available candidates are effective only against mild AD or have side effects. So, a study was planned to synthesis new candidates that may have good potential to treat AD. A series of new anthrarobin acyl derivatives (2–8 were synthesized by the reaction of anthrarobin (1 and acetic anhydride/acyl chlorides. The product were characterized by 1H NMR and EI-MS, and evaluated for butyrylcholinesterase (BuChE inhibition activity. Compounds 5 and 4 showed notable BuChE inhibitory potential with IC50 5.3 ± 1.23 and 17.2 ± 0.47 μM, respectively when compared with the standard eserine (IC50 7.8 ± 0.27 μM, compound 5 showed potent BuChE inhibition potential than the standard eserine. The active compounds 5 and 4 have acyl groups at 2-OH and 10-OH positions which may be responsible for inhibitory potential as this orientation is absent in other products. In silico studies of 5 and 4 products revealed the high inhibitory potential due to stable binding of ligand with the BuChE active sites with docking energy score −18.8779 kcal/mol and −23.1159 kcal/mol, respectively. Subsequently, compound 5 that have potent BuChE inhibitory activity could be the potential candidate for drug development for Alzheimer’s disease.

  6. Unexpected Reaction Pathway for butyrylcholinesterase-catalyzed inactivation of “hunger hormone” ghrelin

    Science.gov (United States)

    Yao, Jianzhuang; Yuan, Yaxia; Zheng, Fang; Zhan, Chang-Guo

    2016-02-01

    Extensive computational modeling and simulations have been carried out, in the present study, to uncover the fundamental reaction pathway for butyrylcholinesterase (BChE)-catalyzed hydrolysis of ghrelin, demonstrating that the acylation process of BChE-catalyzed hydrolysis of ghrelin follows an unprecedented single-step reaction pathway and the single-step acylation process is rate-determining. The free energy barrier (18.8 kcal/mol) calculated for the rate-determining step is reasonably close to the experimentally-derived free energy barrier (~19.4 kcal/mol), suggesting that the obtained mechanistic insights are reasonable. The single-step reaction pathway for the acylation is remarkably different from the well-known two-step acylation reaction pathway for numerous ester hydrolysis reactions catalyzed by a serine esterase. This is the first time demonstrating that a single-step reaction pathway is possible for an ester hydrolysis reaction catalyzed by a serine esterase and, therefore, one no longer can simply assume that the acylation process must follow the well-known two-step reaction pathway.

  7. Monitoring of plasma butyrylcholinesterase activity and hematological parameters in pesticide sprayers.

    Science.gov (United States)

    Rastogi, S K; Singh, Vipul K; Kesavachandran, C; Jyoti; Siddiqui, M K J; Mathur, N; Bharti, R S

    2008-04-01

    To evaluate the health impact of spraying organophosphorus insecticides (OPs), 34 male sprayers in the mango belt of Malihabad, a small town located 27 km from Lucknow in North India was selected. Plasma butyryl cholinesterase (PBChE) and complete blood count were assessed among sprayers after spraying pesticides and the findings obtained were compared with those determined in a reference group (n = 18). The most common symptoms observed were burning sensation in the eyes (8.82%), itching/skin irritation (23.52%) and chest symptoms (32.35%) in the exposed workers. Plasma butyrylcholinesterase (PBChE) was significantly decreased in workers. The results indicated significant decrease in the mean value of hemoglobin, hematocrit and platelets count; however, significantly higher count of leukocytes was also observed in the exposed group (sprayers) compared to that observed in the control group (P < 0.05). Monitoring of PBChE in pesticide sprayers could be useful to predict and prevent health hazards of OPs.

  8. Association between butyrylcholinesterase K variant and mild cognitive impairment in the Thai community-dwelling patients.

    Science.gov (United States)

    Pongthanaracht, Natsalil; Yanarojana, Somchai; Pinthong, Darawan; Unchern, Supeenun; Thithapandha, Amnuay; Assantachai, Prasert; Supavilai, Porntip

    2017-01-01

    To study the association of the butyrylcholinesterase K variant (BChE-K) and the plasma BChE activity with mild cognitive impairment (MCI) in Thai community-dwelling patients. One hundred patients diagnosed with MCI and 100 control subjects were recruited from the community-dwelling setting in Bangkok, Thailand. The genotype and allele distributions of the BChE-K were determined by polymerase chain reaction and subsequent DNA sequencing. The BChE activity was measured in plasma according to the Ellman's method. The BChE-K allele frequencies in the Thai community-dwelling patients were in accordance with other ethnics. The BChE-K allele frequency in the control subjects (12%) was higher than that of MCI patients (5.5%), suggesting a protective role of BChE-K for MCI in the Thai community-dwelling patients. The BChE-K homozygotes were significantly associated with lower BChE activity. Our results suggested that the BChE-K may be implicated as a protective factor for MCI in the Thai community-dwelling patients, although a further study with a large sample size is warranted to confirm this.

  9. Direct effects of locally administered lipopolysaccharide on glucose, lipid, and protein metabolism in the placebo-controlled, bilaterally infused human leg

    DEFF Research Database (Denmark)

    Buhl, Mads; Bosnjak, Ermina; Vendelbo, Mikkel H.

    2013-01-01

    Context: Accumulating evidence suggests that chronic exposure to lipopolysaccharide (LPS, endotoxin) maycreate a constant low-grade inflammation, leading to insulin resistance and diabetes. All previous human studies assessing the metabolic actions of LPS have used systemic administration, making...... palmitate isotopic dilution, although primary ANOVA tests did not reveal significant dilution. Leg blood flows, phenylalanine, lactate kinetics, cytokines, and intramyocellular insulin signaling were not affected by LPS. LPS thus directly inhibits insulin-stimulated glucose uptake and increases palmitate...... and stress hormone release may lead to overt glucose intolerance and diabetes....

  10. Tocopherol isomer pattern in serum and stool of human following consumption of black currant seed press residue administered in whole grain bread.

    Science.gov (United States)

    Helbig, Dorit; Wagner, Andreas; Schubert, Rainer; Jahreis, Gerhard

    2009-12-01

    Serum gamma-tocopherol is thought to be associated with human health. The dietary influence of tocopherol and fibre-rich black currant seed press residue on serum and stool tocopherol concentration was investigated in a controlled human intervention study. Thirty-six women consumed bread enriched with black currant press residue (4 weeks). The resultant faecal and serum tocopherol concentrations were compared with those after a period consuming control bread without press residue and a normal baseline diet. Fibre intake and excretion, antioxidant capacity (TEAC), and vitamin C concentrations in serum and urine were also determined. Samples were obtained with a 5-day standardised diet at the end of each period. The press residue bread lead to significantly increased beta-, gamma-, delta- and total tocopherol intake, serum alpha-, beta-, gamma- and total tocopherol concentration (with and without lipid adjustment), fibre intake and urinary vitamin C concentration compared to control bread (Pconsumption could be due to a presumed interruption of the enzymatic tocopherol degradation mechanism by bread constituents.

  11. Magnetic Fe3O4@TiO2 Nanoparticles-based Test Strip Immunosensing Device for Rapid Detection of Phosphorylated Butyrylcholinesterase

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Xiaoxiao; Zhang, Weiying; Lin, Yuehe; Du, Dan

    2013-12-15

    An integrated magnetic nanoparticles-based test-strip immunosensing device was developed for rapid and sensitive quantification of phosphorylated butyrylcholinesterase (BChE), the biomarker of exposure to organophosphous pesticides (OP), in human plasma. In order to overcome the difficulty in scarce availability of OP-specific antibody, here magnetic Fe3O4@TiO2 nanoparticles were used and adsorbed on the test strip through a small magnet inserted in the device to capture target OP-BChE through selective binding between TiO2 and OP moiety. Further recognition was completed by horseradish peroxidase (HRP) and anti-BChE antibody (Ab) co-immobilized gold nanoparticles (GNPs). Their strong affinities among Fe3O4@TiO2, OP-BChE and HRP/Ab-GNPs were characterized by quartz crystal microbalance (QCM), surface plasmon resonance (SPR) and square wave voltammetry (SWV) measurements. After cutting off from test strip, the resulted immunocomplex (HRP/Ab-GNPs/OP-BChE/Fe3O4@TiO2) was measured by SWV using a screen printed electrode under the test zone. Greatly enhanced sensitivity was achieved by introduction of GNPs to link enzyme and antibody at high ratio, which amplifies electrocatalytic signal significantly. Moreover, the use of test strip for fast immunoreactions reduces analytical time remarkably. Coupling with a portable electrochemical detector, the integrated device with advanced nanotechnology displays great promise for sensitive, rapid and in-filed on-site evaluation of OP poisoning.

  12. Effectiveness of the VOICES/VOCES sexually transmitted disease/human immunodeficiency virus prevention intervention when administered by health department staff: does it work in the "real world"?

    Science.gov (United States)

    Neumann, Mary Spink; O'Donnell, Lydia; Doval, Alexi San; Schillinger, Julia; Blank, Susan; Ortiz-Rios, Elizabeth; Garcia, Trinidad; O'Donnell, Carl R

    2011-02-01

    Prevention providers wonder whether benefits achieved in the original, researcher-led, efficacy trials of interventions are replicated when the intervention is delivered in real-world settings by their agency's staff. A replication study was conducted at 2 public sexually transmitted disease (STD) clinics (New York City and San Juan, PR). Using a controlled trial design, intervention (VOICES/VOCES) and comparison conditions (regular clinic services) were assigned in alternating 4-week blocks. Trained agency staff delivered the intervention. Effectiveness was assessed for incident STDs, redemption of coupons for condoms at neighborhood location after the visit, and improved knowledge and attitudes about STDs and condoms. A total of 3365 patients were recruited, completed the protocol, and followed through STD surveillance systems for an average of 17 months. Of 397 with an incident infection, 226 (13.4%) were among those enrolled during comparison blocks; 171 were among those in the intervention condition (10.2%). Controlling for site and gender, participants enrolled during intervention blocks were significantly less likely to have an incident STD reported to the surveillance system (hazard ratio, 0.78; 95% confidence interval, 0.64-0.96). Intervention block participants scored higher on scales of STD knowledge (4.89 vs. 3.87, P VOCES redeemed condoms (P < 0.05). Positive effects were more consistent in New York, which may be related to fidelity of implementation. A packaged human immunodeficiency virus prevention intervention can be delivered by agencies, with benefits similar to those achieved in the research setting.

  13. Plasma growth hormone response to human growth hormone releasing factor in rats administered with chlorpromazine and antiserum against somatostatin. Effects of hypo- and hyperthyroidism.

    Science.gov (United States)

    Wakabayashi, I; Tonegawa, Y; Ihara, T; Hattori, M; Shibasaki, T; Ling, N

    1985-10-01

    The effect of hypo- and hyperthyroidism on the plasma growth hormone (GH) response to synthetic human growth hormone releasing factor (GRF) was determined in conscious, freely moving rats pretreated with chlorpromazine and antiserum against somatostatin. Chlorpromazine plus somatostatin antiserum pretreated rats gave consistent response to GRF which was not observed in untreated rats. Chlorpromazine alone has no effect on GH secretion induced by GRF in rat pituitary monolayer culture. In rats made hypothyroid by thyroidectomy, both basal and peak plasma GH responses to a small (0.25 microgram/kg bw) and a moderate dose of GRF (1 microgram/kg bw) were significantly reduced as compared to controls. In rats made hyperthyroid by the administration of thyroxine, basal and peak plasma GH responses to a small but not to a moderate dose of GRF were significantly reduced as compared to controls. A reduced plasma GH response to a small dose of GRF was observed 8 days after the cessation of thyroxine administration. The pituitary GH reserve was markedly reduced in hypothyroid but not in hyperthyroid rats as compared to their respective controls. These results indicate that plasma GH response to GRF is reduced both in hypo- and hyperthyroidism. The mechanism involved in the phenomenon appears to be different between the two conditions.

  14. Subcutaneously administered Menopur(R, a new highly purified human menopausal gonadotropin, causes significantly fewer injection site reactions than Repronex(R in subjects undergoing in vitro fertilization

    Directory of Open Access Journals (Sweden)

    Somkuti Stephen

    2005-11-01

    Full Text Available Abstract Background The safety and tolerability of a new highly purified, urine-derived human menopausal gonadotropin (hMG preparation [Menopur(R] was compared with a currently available hMG [Repronex (R] in women undergoing in vitro fertilization (IVF. Methods This was a randomized, open-label, parallel-group, multicenter study conducted in subjects undergoing IVF. Women (N = 125, 18–39 years of age, underwent pituitary down-regulation with leuprolide acetate beginning 7 days prior to onset of menses and continuing up to the day before hCG administration. Subjects were randomized to receive subcutaneous (SC Menopur (R (n = 61 or Repronex (R SC (n = 64 for a maximum of 12 days. All adverse events (AEs were recorded and subject self-assessments of injection site reactions were recorded in a daily diary. Results Significantly fewer subjects in the Menopur (R group reported injection site reactions (P Conclusion Menopur (R SC offers a greater safety and tolerability profile compared to Repronex (R SC.

  15. Radiotoxicity of systemically administered 211At-labeled human/mouse chimeric monoclonal antibody: a long-term survival study with histologic analysis

    International Nuclear Information System (INIS)

    McLendon, Roger E.; Archer, Gary E.; Larsen, Roy H.; Akabani, Gamal; Bigner, Darell D.; Zalutsky, Michael R.

    1999-01-01

    Purpose: The antitenascin human/mouse chimeric monoclonal antibody labeled with the α-particle-emitting radionuclide 211 At is of interest as an endo radiotherapeutic agent for the treatment of brain tumors. To facilitate the investigation of 211 At-labeled chimeric 81C6 in patients, the long-term radiotoxicity of this radiopharmaceutical has been evaluated. Methods and Materials: Antibody labeling was performed using N-succinimidyl 3-[ 211 At]astato-benzoate. After an initial dose-finding experiment, a second toxicity study was carried out at 4 dose levels in groups of 30 non thyroid blocked B6C3F 1 mice per group (15 males, 15 females). Male mice received either saline or 15-81 kBq/g and females received either saline or 16-83 kBq/g of 211 At-labeled antibody. Ten animals (5 males, 5 females) were followed for 6 months and the remainder for 1 year. Results: The lethal dose in 10% of animals (LD 10 ) for 211 At-labeled chimeric 81C6 was 46 kBq/g in females and 102 kBq/g in males. Toxic effects--perivascular fibrosis of the intraventricular septum of the heart, bone marrow suppression, splenic white pulp atrophy, and spermatic maturational delay--generally were confined to a few animals receiving the highest doses of labeled antibody. Conclusions: The LD 10 of 211 At-labeled chimeric 81C6 in this mouse strain was about half that of [ 211 At]astatide. These results establish the preclinical maximum tolerated dose of 211 At-labeled chimeric 81C6 and define in the mouse the target organs for toxicity. These studies will be useful for determining starting doses for clinical studies with 211 At-labeled chimeric 81C6

  16. Chemometrics-assisted Spectrofluorimetric Determination of Two Co-administered Drugs of Major Interaction, Methotrexate and Aspirin, in Human Urine Following Acid-induced Hydrolysis.

    Science.gov (United States)

    Maher, Hadir M; Ragab, Marwa A A; El-Kimary, Eman I

    2015-01-01

    Methotrexate (MTX) is widely used to treat rheumatoid arthritis (RA), mostly along with non-steroidal anti-inflammatory drugs (NSAIDs), the most common of which is aspirin or acetyl salicylic acid (ASA). Since NSAIDs impair MTX clearance and increase its toxicity, it was necessary to develop a simple and reliable method for the monitoring of MTX levels in urine samples, when coadministered with ASA. The method was based on the spectrofluorimetric measurement of the acid-induced hydrolysis product of MTX, 4-amino-4-deoxy-10-methylpteroic acid (AMP), along with the strongly fluorescent salicylic acid (SA), a product of acid-induced hydrolysis of aspirin and its metabolites in urine. The overlapping emission spectra were resolved using the derivative method (D method). In addition, the corresponding derivative emission spectra were convoluted using discrete Fourier functions, 8-points sin xi polynomials, (D/FF method) for better elimination of interferences. Validation of the developed methods was carried out according to the ICH guidelines. Moreover, the data obtained using derivative and convoluted derivative spectra were treated using the non-parametric Theil's method (NP), compared with the least-squares parametric regression method (LSP). The results treated with Theil's method were more accurate and precise compared with LSP since the former is less affected by the outliers. This work offers the potential of both derivative and convolution using discrete Fourier functions in addition to the effectiveness of using the NP regression analysis of data. The high sensitivity obtained by the proposed methods was promising for measuring low concentration levels of the two drugs in urine samples. These methods were efficiently used to measure the drugs in human urine samples following their co-administration.

  17. Evaluating Controlled Human Malaria Infection in Kenyan Adults with Varying Degrees of Prior Exposure to Plasmodium falciparum using sporozoites administered by intramuscular injection

    Directory of Open Access Journals (Sweden)

    Susanne Helena Hodgson

    2014-12-01

    Full Text Available Background: Controlled human malaria infection (CHMI studies are a vital tool to accelerate vaccine and drug development. As CHMI trials are performed in a controlled environment, they allow unprecedented, detailed evaluation of parasite growth dynamics (PGD and immunological responses. However, CHMI studies have not been routinely performed in malaria-endemic countries or used to investigate mechanisms of naturally-acquired immunity (NAI to Plasmodium falciparum. Methods: We conducted an open-label, randomized CHMI pilot-study using aseptic, cryopreserved P. falciparum sporozoites (PfSPZ Challenge to evaluate safety, infectivity and PGD in Kenyan adults with low to moderate prior exposure to P. falciparum (Pan African Clinical Trial Registry: PACTR20121100033272. Results: All participants developed blood-stage infection confirmed by qPCR. However one volunteer (110 remained asymptomatic and blood-film negative until day 21 post-injection of PfSPZ Challenge. This volunteer had a reduced parasite multiplication rate (PMR (1.3 in comparison to the other 27 volunteers (median 11.1. A significant correlation was seen between PMR and screening anti-schizont ELISA OD (p=0.044, R=-0.384 but not when volunteer 110 was excluded from the analysis (p=0.112, R=-0.313. Conclusions: PfSPZ Challenge is safe and infectious in malaria-endemic populations and could be used to assess the efficacy of malaria vaccines and drugs in African populations. Whilst our findings are limited by sample size, our pilot study has demonstrated for the first time that NAI may impact on PMR post-CHMI in a detectable fashion, an important finding that should be evaluated in further CHMI studies.

  18. Reduced butyrylcholinesterase activity is an early indicator of trauma-induced acute systemic inflammatory response

    Directory of Open Access Journals (Sweden)

    Zivkovic AR

    2016-11-01

    Full Text Available Aleksandar R Zivkovic, Jochen Bender, Thorsten Brenner, Stefan Hofer,* Karsten Schmidt* Department of Anesthesiology, Heidelberg University Hospital, Heidelberg, Germany *These authors contributed equally to this work Purpose: Early diagnosis of systemic inflammatory response syndrome is fundamentally important for an effective and a goal-directed therapy. Various inflammation biomarkers have been used in clinical and experimental practice. However, a definitive diagnostic tool for an early detection of systemic inflammation remains to be identified. Acetylcholine (Ach has been shown to play an important role in the inflammatory response. Serum cholinesterase (butyrylcholinesterase [BChE] is the major Ach hydrolyzing enzyme in blood. The role of this enzyme during inflammation has not yet been fully understood. This study tests whether a reduction in the BChE activity could indicate the onset of the systemic inflammatory response upon traumatic injury. Patients and methods: This observational study measured BChE activity in patients with traumatic injury admitted to the emergency room by using point-of-care-test system (POCT. In addition, the levels of routine inflammation biomarkers during the initial treatment period were measured. Injury Severity Score was used to assess the trauma severity. Results: Altered BChE activity was correlated with trauma severity, resulting in systemic inflammation. Reduction in the BChE activity was detected significantly earlier compared to those of routinely measured inflammatory biomarkers. Conclusion: This study suggests that the BChE activity reduction might serve as an early indicator of acute systemic inflammation. Furthermore, BChE activity, measured using a POCT system, might play an important role in the early diagnosis of the trauma-induced systemic inflammation. Keywords: trauma, injury, early diagnostics, cholinergic, pseudocholinesterase, SIRS

  19. Acetylcholinesterase and butyrylcholinesterase inhibitory activity of some selected Nigerian medicinal plants

    Directory of Open Access Journals (Sweden)

    Taiwo O. Elufioye

    Full Text Available Plants have been found to be useful as memory enhansers as well as antiaging. Twenty two of such plants from sixteen families were investigated for their acetylcholinesterase (AChE and butyrylcholinesterase (BuChE inhibitory activities using the in vitro Ellman's spectrophotometric and in situ bioautographic methods with physostigmine as standard. At least three morphological parts were examined for each of the plants investigated and the test concentration was 42.5 µg/ mL. Some plants were active on both enzymes though with some morphological parts being more active than others. The root bark of Spondias mombin showed the highest activity to the two enzymes; 64.77% and 83.94% on AChE and BuChE respectively. Other plant parts of the selected plants exhibited some remarkable selectivity in their actions. Those selectively active against AChE were Alchornia laxiflora stem bark (41.12% and root bark, Callophyllum inophyllurn root bark (56.52%. The leaves of C. jagus (74.25%, Morinda lucida leaves (40.15%, Peltophorum pterocarpum leaves and stem bark (49.5% and 68.85%, respectively, physiostigmine gave 90.31% inhibition. Generally higher activities were found against BuChE. Bombax bromoposenze leaves, root bark and stem bark were particularly active. The inhibition was over 80%. Other selective plant parts are the leaves Antiaris africana, Cissampelos owarensis aerial parts (78.96%, Combretum molle leaves and stem bark (90.42% and 88.13%, respectively, Dioscorea dumentorum root bark and tuber (over 87%, G. kola leaves, Markhamia tomentosa root bark, Pycnanthus angolensis stem bark and Tetrapleura tetraptera leaves. Most of these plants are taken as food or are food ingredients in Nigeria and may account for the low incidence of Alzheimer's disease in the country and may play certain roles in the mediation of the disease.

  20. Effects of energetic restriction diet on butyrylcholinesterase in obese women from southern Brazil - A longitudinal study.

    Science.gov (United States)

    Santos, Willian Dos; Tureck, Luciane Viater; Saliba, Louise Farah; Schenknecht, Caroline Schovanz; Scaraboto, Débora; Souza, Ricardo Lehtonen R; Furtado-Alle, Lupe

    2017-01-01

    Butyrylcholinesterase (BChE) activity has been associated with obesity, lipid concentrations, and CHE2 locus phenotypes. This, the aim of this study was to evaluate the effects of an energetic restriction diet intervention on anthropometrical and biochemical variables and on absolute and relative BChE activity in CHE2 C5+ and CHE2 C5- individuals. One hundred eleven premenopausal obese women from Southern Brazil participated in an energetic restriction diet intervention (deficit of 2500 kJ/day) for 8 weeks. Their anthropometric and biochemical parameters were evaluated before and after the intervention. Plasma BChE activity was measured, and BChE bands in plasma and CHE2 locus phenotypes were detected by electrophoresis. The dietetic intervention decreased anthropometric and biochemical parameters as well as absolute BChE activity and relative activity of the G4 band. The CHE2 C5+ phenotype presented a different effect when compared with the CHE2 C5- phenotype. The CHE2 C5+ phenotype showed an effect in absolute BChE activity and in the relative activity of the G4 form, maintaining higher BChE activity regardless of the metabolic changes. In our study, 8 weeks was not sufficient time to lower the body mass index to normal, but it was enough to significantly reduce the absolute BChE activity, which became similar to the levels in nonobese individuals. CHE2 C5+ individuals were resistant to the decrease in BChE activity compared to CHE2 C5- individuals. This shows that the diet did not affect the CHE2 and G4 fraction complex and that the products of the CHE2 locus in association with BChE have a role in energy metabolism, maintaining high levels of enzymatic activity even after dietary intervention.

  1. Activity of essential oils and individual components against acetyl- and butyrylcholinesterase.

    Science.gov (United States)

    Orhan, Ilkay; Kartal, Murat; Kan, Yüksel; Sener, Bilge

    2008-01-01

    We have tested acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of nineteen essential oils obtained from cultivated plants, namely one from Anethum graveolens L. (organic fertilizer), two from Foeniculum vulgare Mill. collected at fully-mature and flowering stages (organic fertilizer), two from Melissa officinalis L. (cultivated using organic and chemical fertilizers), two from Mentha piperita L. and M. spicata L. (organic fertilizer), two from Lavandula officinalis Chaix ex Villars (cultivated using organic and chemical fertilizers), two from Ocimum basilicum L. (green and purple-leaf varieties cultivated using only organic fertilizer), four from Origanum onites L., O. vulgare L., O. munitiflorum Hausskn., and O. majorana L. (cultivated using organic fertilizer), two from Salvia sclarea L. (organic and chemical fertilizers), one from S. officinalis L. (organic fertilizer), and one from Satureja cuneifolia Ten. (organic fertilizer) by a spectrophotometric method of Ellman using ELISA microplate-reader at 1 mg/ml concentration. In addition, a number of single components widely encountered in most of the essential oils [gamma-terpinene, 4-allyl anisole, (-)-carvone, dihydrocarvone, (-)-phencone, cuminyl alcohol, cumol, 4-isopropyl benzaldehyde, trans-anethole, camphene, iso-borneol, (-)-borneol, L-bornyl acetate, 2-decanol, 2-heptanol, methyl-heptanol, farnesol, nerol, iso-pulegol, 1,8-cineole, citral, citronellal, citronellol, geraniol, linalool, alpha-pinene, beta-pinene, piperitone, iso-menthone, menthofurane, linalyl oxide, linalyl ester, geranyl ester, carvacrol, thymol, menthol, vanilline, and eugenol] was also screened for the same activity in the same manner. Almost all of the essential oils showed a very high inhibitory activity (over 80%) against both enzymes, whereas the single components were not as active as the essential oils.

  2. Reference values for acetyl and butyrylcholinesterases in cattle under actual management conditions, hepatic and renal function by application of chlorpyrifos.

    Science.gov (United States)

    Ferré, Daniela M; Lentini, Valeria R; Romano, R Raquel; Ludueña, Hector R; Jotallán, Paola J; Gorla, Nora B M

    2018-03-04

    Chlorpyrifos is an anticholinesterase organophosphate insecticide widely used in Argentina in the production of food derived from animal, fruit and horticultural origin and is reported as a residue within these products. Local reference values for acetyl and butyrylcholinesterase were determined in Aberdeen Angus bovine and cross bred cattle (n = 25), a requirement to be able to evaluate toxicity of commercial organophosphate and carbamate formulations. The activity of cholinesterase enzymes presented an overall mean of 2,183.00 ± 485.6 IU L -1 for erythrocyte acetylcholinesterase and 203.1 ± 42.06 IU L -1 for plasma butyrylcholinesterase, which are used as reference values for meat steers within a system of intensive production in a semi-arid region. The toxic potential of chlorpyrifos in steers of the same breeds (n = 12) was assessed applying chlorpyrifos 15.00% Tipertox® in a single therapeutic dose of 7.50 mg kg -1 by topical route. Prior to application and then on day 1 and day 21 post-application, both blood cholinesterases, serum chlorpyrifos concentration by ultra-high resolution liquid chromatography with mass detector, analysis of blood counts, total proteins, liver enzymes, urea and creatinine were evaluated. The mean plasma concentration of chlorpyrifos was 27.90 ug L -1 at 24 h. The findings indicate that the therapeutic treatment of castrated male bovines treated with chlorpyrifos, applied by pour-on according to the manufacturer's instructions, does not cause changes in the variables evaluated.

  3. Inhibition of plasma butyrylcholinesterase activity in the lizard Gallotia galloti palmae by pesticides: a field study

    International Nuclear Information System (INIS)

    Sanchez-Hernandez, Juan C.; Carbonell, R.; Henriquez Perez, A.; Montealegre, M.; Gomez, L.

    2004-01-01

    A field study was performed to evaluate the effect of exposure to organophosphorus (OP) and carbamate (CB) pesticides on the lizard Gallotia galloti palmae. Butyrylcholinesterase (BChE) activity was measured in the plasma of 420 lizards collected from agricultural and reference areas on the Island of La Palma (Canary Islands, Spain) in two sampling periods. Exposure to cholinesterase-inhibiting pesticides was evaluated by a statistical criterion based on a threshold value (two standard deviations below the mean enzyme activity) calculated for the reference group, and a chemical criterion based on the in vitro reactivation of BChE activity using pyridine-2-aldoxime methochloride (2-PAM) or after water dilution of the sample. Mean (±SD) BChE activity for lizards from agricultural areas was significantly lower (Fuencaliente site = 2.00 ± 0.98 μmol min -1 ml -1 , Tazacorte site = 2.88 ± 1.08) than that for lizards from the reference areas (Los Llanos site = 3.06 ± 1.17 μmol min -1 ml -1 , Tigalate site = 3.96 ± 1.62). According to the statistical criterion, the number of lizards with BChE depressed was higher at Fuencaliente (22% of males and 25.4% of females) than that sampled at Tazacorte (7.8% of males and 6.2% of females). According to the chemical criterion, Fuencaliente also yielded a higher number of individuals (112 males and 47 females) with BChE activity inhibited by both OP and CB pesticides. CBs appeared to be the pesticides most responsible for BChE inhibition because most of the samples showed reactivation of BChE activity after water treatment (63.3% from Fuencaliente and 29% from Tazacorte). We concluded that the use of reactivation techniques on plasma BChE activity is a better and more accurate method for assessing field exposure to OP/CB pesticides in this lizard species than making direct comparisons of enzyme activity levels between sampling areas. - Capsule: Chemical reactivation of lizard BChE activity is a suitable diagnostic method for

  4. First-in-Human Evaluation of the Safety and Immunogenicity of an Intranasally Administered Replication-Competent Sendai Virus–Vectored HIV Type 1 Gag Vaccine: Induction of Potent T-Cell or Antibody Responses in Prime-Boost Regimens

    Science.gov (United States)

    Nyombayire, Julien; Anzala, Omu; Gazzard, Brian; Karita, Etienne; Bergin, Philip; Hayes, Peter; Kopycinski, Jakub; Omosa-Manyonyi, Gloria; Jackson, Akil; Bizimana, Jean; Farah, Bashir; Sayeed, Eddy; Parks, Christopher L.; Inoue, Makoto; Hironaka, Takashi; Hara, Hiroto; Shu, Tsugumine; Matano, Tetsuro; Dally, Len; Barin, Burc; Park, Harriet; Gilmour, Jill; Lombardo, Angela; Excler, Jean-Louis; Fast, Patricia; Laufer, Dagna S.; Cox, Josephine H.

    2017-01-01

    Background. We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)–vectored, human immunodeficiency virus type 1 (HIV-1) vaccine. Methods. Sixty-five HIV-1–uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35–vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (SLA); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (SHA); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (ASH); and priming and boosting with a higher-dose SeV-Gag given intranasally (SHSH). Results. All vaccine regimens were well tolerated. Gag-specific IFN-γ enzyme-linked immunospot–determined response rates and geometric mean responses were higher (96% and 248 spot-forming units, respectively) in groups primed with SeV-Gag and boosted with Ad35-GRIN (SLA and SHA) than those after a single dose of Ad35-GRIN (56% and 54 spot-forming units, respectively) or SeV-Gag (55% and 59 spot-forming units, respectively); responses persisted for ≥8 months after completion of the prime-boost regimen. Functional CD8+ T-cell responses with greater breadth, magnitude, and frequency in a viral inhibition assay were also seen in the SLA and SHA groups after Ad35-GRIN boost, compared with those who received either vaccine alone. SeV-Gag did not boost T-cell counts in the ASH group. In contrast, the highest Gag-specific antibody titers were seen in the ASH group. Mucosal antibody responses were sporadic. Conclusions. SeV-Gag primed functional, durable HIV-specific T

  5. First-in-Human Evaluation of the Safety and Immunogenicity of an Intranasally Administered Replication-Competent Sendai Virus-Vectored HIV Type 1 Gag Vaccine: Induction of Potent T-Cell or Antibody Responses in Prime-Boost Regimens.

    Science.gov (United States)

    Nyombayire, Julien; Anzala, Omu; Gazzard, Brian; Karita, Etienne; Bergin, Philip; Hayes, Peter; Kopycinski, Jakub; Omosa-Manyonyi, Gloria; Jackson, Akil; Bizimana, Jean; Farah, Bashir; Sayeed, Eddy; Parks, Christopher L; Inoue, Makoto; Hironaka, Takashi; Hara, Hiroto; Shu, Tsugumine; Matano, Tetsuro; Dally, Len; Barin, Burc; Park, Harriet; Gilmour, Jill; Lombardo, Angela; Excler, Jean-Louis; Fast, Patricia; Laufer, Dagna S; Cox, Josephine H

    2017-01-01

     We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)-vectored, human immunodeficiency virus type 1 (HIV-1) vaccine.  Sixty-five HIV-1-uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35-vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (S L A); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (S H A); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (AS H ); and priming and boosting with a higher-dose SeV-Gag given intranasally (S H S H ).  All vaccine regimens were well tolerated. Gag-specific IFN-γ enzyme-linked immunospot-determined response rates and geometric mean responses were higher (96% and 248 spot-forming units, respectively) in groups primed with SeV-Gag and boosted with Ad35-GRIN (S L A and S H A) than those after a single dose of Ad35-GRIN (56% and 54 spot-forming units, respectively) or SeV-Gag (55% and 59 spot-forming units, respectively); responses persisted for ≥8 months after completion of the prime-boost regimen. Functional CD8 + T-cell responses with greater breadth, magnitude, and frequency in a viral inhibition assay were also seen in the S L A and S H A groups after Ad35-GRIN boost, compared with those who received either vaccine alone. SeV-Gag did not boost T-cell counts in the AS H group. In contrast, the highest Gag-specific antibody titers were seen in the AS H group. Mucosal antibody responses were sporadic.  SeV-Gag primed functional, durable HIV-specific T-cell responses and boosted antibody

  6. Synthesis of (E)-N'-[1-(2,4-Dihydroxyphenyl)ethylidene]substituted hydrazides as possible alpha-glucosidase and butyrylcholinesterase Inhibitors

    International Nuclear Information System (INIS)

    Abbasi, M.A.; Shah, S.A.H.; Siddiqui, S.Z.; Khan, K.M.

    2017-01-01

    In the current research work, (E)-N'-[1-(2,4-dihydroxyphenyl)ethylidene]substituted hydrazides were synthesized in a couple of steps and their enzyme inhibition potential was analyzed. Firstly 2,4-hydroxyacetophenone (1) was reacted with hydrated hydrazine (2) under stirring to yield (E)-4-(1-hydrazonoethyl)benzene-1,3-diol (3) which was further reacted with different acid halides, (4a-i) to afford (E)-[1-(2,4-dihydroxyphenyl)ethylidene]substituted hydrazides (5a-i). These synthesized compounds were characterized by EI-MS, 1H-NMR spectral techniques and were also evaluated against a-glucosidase and butyrylcholinesterase enzymes. The synthesized compounds were found to be acceptable inhibitors of a-glucosidase and decent inhibition against butyrylcholinesterase. (author)

  7. Large-scale studies of the functional K variant of the butyrylcholinesterase gene in relation to Type 2 diabetes and insulin secretion

    DEFF Research Database (Denmark)

    Johansen, A; Nielsen, E-M D; Andersen, G

    2004-01-01

    Polymorphisms of the butyrylcholinesterase gene (BCHE) are reported to associate with Alzheimer's disease and a recent study found a significant association of the BCHE K variant (G1615A/Ala539Thr) with Type 2 diabetes. The objectives of our study were to examine whether the BCHE K variant is ass...... is associated with Type 2 diabetes or estimates of pancreatic beta cell function in large-scale populations of glucose-tolerant Caucasians....

  8. Safety and tolerability of conserved region vaccines vectored by plasmid DNA, simian adenovirus and modified vaccinia virus ankara administered to human immunodeficiency virus type 1-uninfected adults in a randomized, single-blind phase I trial.

    Directory of Open Access Journals (Sweden)

    Emma-Jo Hayton

    Full Text Available HIV-1 vaccine development has advanced slowly due to viral antigenic diversity, poor immunogenicity and recently, safety concerns associated with human adenovirus serotype-5 vectors. To tackle HIV-1 variation, we designed a unique T-cell immunogen HIVconsv from functionally conserved regions of the HIV-1 proteome, which were presented to the immune system using a heterologous prime-boost combination of plasmid DNA, a non-replicating simian (chimpanzee adenovirus ChAdV-63 and a non-replicating poxvirus, modified vaccinia virus Ankara. A block-randomized, single-blind, placebo-controlled phase I trial HIV-CORE 002 administered for the first time candidate HIV-1- vaccines or placebo to 32 healthy HIV-1/2-uninfected adults in Oxford, UK and elicited high frequencies of HIV-1-specific T cells capable of inhibiting HIV-1 replication in vitro. Here, detail safety and tolerability of these vaccines are reported.Local and systemic reactogenicity data were collected using structured interviews and study-specific diary cards. Data on all other adverse events were collected using open questions. Serum neutralizing antibody titres to ChAdV-63 were determined before and after vaccination.Two volunteers withdrew for vaccine-unrelated reasons. No vaccine-related serious adverse events or reactions occurred during 190 person-months of follow-up. Local and systemic events after vaccination occurred in 27/32 individuals and most were mild (severity grade 1 and predominantly transient (<48 hours. Myalgia and flu-like symptoms were more strongly associated with MVA than ChAdV63 or DNA vectors and more common in vaccine recipients than in placebo. There were no intercurrent HIV-1 infections during follow-up. 2/24 volunteers had low ChAdV-63-neutralizing titres at baseline and 7 increased their titres to over 200 with a median (range of 633 (231-1533 post-vaccination, which is of no safety concern.These data demonstrate safety and good tolerability of the pSG2

  9. Acute effects of chlorpyryphos-ethyl and secondary treated effluents on acetylcholinesterase and butyrylcholinesterase activities in Carcinus maenas

    Institute of Scientific and Technical Information of China (English)

    Jihene Ghedira; Jamel Jebali; Zied Bouraoui; Mohamed Banni; Lassaad Chouba; Hamadi Boussetta

    2009-01-01

    The acute effects of commercial formulation of chlorpyrifos-ethyl (Dursban(r)) and the secondary treated industrial/urban effluent (STIUE) exposure on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities in hepatopancreas and gills of Mediterranean crab Carcinus maenas were investigated. After 2 d of exposure to chlorpyriphos-ethyl, the AChE activity was inhibited in both organs at concentrations of 3.12 and 7.82 μg/L, whereas the BuChE was inhibited only at higher concentration 7.82 μg/L of commercial preparation Dursban(r). The exposure of crabs to Dursban(r) (3.12 μg/L) showed a significant decrement of AChE activity at 24 and 48 h, whereas the BuChE was inhibited only after 24 h and no inhibition for both enzymes was observed after 72 h. Moreover, a significant repression of AChE activity was observed in both organs of C. maenas exposed to 5% of STIUE. Our experiments indicated that the measurement of AChE activity in gills and hepatopancreas of C. meanas would be useful biomarker of organophosphorous (OP) and of neurotoxic effects of STIUE in Tunisia.

  10. Rosmarinus officinalis L. leaf extract improves memory impairment and affects acetylcholinesterase and butyrylcholinesterase activities in rat brain.

    Science.gov (United States)

    Ozarowski, Marcin; Mikolajczak, Przemyslaw L; Bogacz, Anna; Gryszczynska, Agnieszka; Kujawska, Malgorzata; Jodynis-Liebert, Jadwiga; Piasecka, Anna; Napieczynska, Hanna; Szulc, Michał; Kujawski, Radoslaw; Bartkowiak-Wieczorek, Joanna; Cichocka, Joanna; Bobkiewicz-Kozlowska, Teresa; Czerny, Boguslaw; Mrozikiewicz, Przemyslaw M

    2013-12-01

    Rosmarinus officinalis L. leaf as part of a diet and medication can be a valuable proposal for the prevention and treatment of dementia. The aim of the study was to assess the effects of subchronic (28-fold) administration of a plant extract (RE) (200 mg/kg, p.o.) on behavioral and cognitive responses of rats linked with acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity and their mRNA expression level in the hippocampus and frontal cortex. The passive avoidance test results showed that RE improved long-term memory in scopolamine-induced rats. The extract inhibited the AChE activity and showed a stimulatory effect on BuChE in both parts of rat brain. Moreover, RE produced a lower mRNA BuChE expression in the cortex and simultaneously an increase in the hippocampus. The study suggests that RE led to improved long-term memory in rats, which can be partially explained by its inhibition of AChE activity in rat brain. © 2013. Published by Elsevier B.V. All rights reserved.

  11. Effect of Acetylcholinesterase and Butyrylcholinesterase on Intrauterine Insemination, Contribution to Inflammations, Oxidative Stress and Antioxidant Status; A Preliminary Report

    Science.gov (United States)

    Haghnazari, Lida; Vaisi-Raygani, Asad; Keshvarzi, Farahnaz; Ferdowsi, Farivar; Goodarzi, Massoud; Rahimi, Zohreh; Baniamerian, Hossin; Tavilani, Haidar; Vaisi-Raygani, Hadis; Vaisi-Raygani, Hessam; Pourmotabbed, Tayehbeh

    2016-01-01

    Background: Oxidative stress affects women fertility and influences on the sperm quality by alterating activities of cholinesterases, a molecular marker of stress-related infertility. The aim of the present study was to investigate the role of acetyl-cholinesterase (AChE), butyrylcholinesterase (BuChE) activities and phenotypes in patients with unexplained infertility (idiopathic). It’s possible association with inflammation marker C-reactive protein (CRP) and other oxidative stress markers, i.e. before and after intra uterine insemination (IUI). Methods: In this study, blood samples of 60 patients with unexplained infertility were collected the day before and 24 hr after IUI (between 8 AM and 9 AM after the overnight fasting) and activities of BuChE, AChE, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GpX) and serum levels of thiol proteins (TP), C-reactive protein (CRP), total antioxidant capacity (TAC) were measured. Statistical significance was assumed at poxidative stress and inflammation and reduction in fertility rates by IUI. PMID:27478769

  12. Photography by Cameras Integrated in Smartphones as a Tool for Analytical Chemistry Represented by an Butyrylcholinesterase Activity Assay.

    Science.gov (United States)

    Pohanka, Miroslav

    2015-06-11

    Smartphones are popular devices frequently equipped with sensitive sensors and great computational ability. Despite the widespread availability of smartphones, practical uses in analytical chemistry are limited, though some papers have proposed promising applications. In the present paper, a smartphone is used as a tool for the determination of cholinesterasemia i.e., the determination of a biochemical marker butyrylcholinesterase (BChE). The work should demonstrate suitability of a smartphone-integrated camera for analytical purposes. Paper strips soaked with indoxylacetate were used for the determination of BChE activity, while the standard Ellman's assay was used as a reference measurement. In the smartphone-based assay, BChE converted indoxylacetate to indigo blue and coloration was photographed using the phone's integrated camera. A RGB color model was analyzed and color values for the individual color channels were determined. The assay was verified using plasma samples and samples containing pure BChE, and validated using Ellmans's assay. The smartphone assay was proved to be reliable and applicable for routine diagnoses where BChE serves as a marker (liver function tests; some poisonings, etc.). It can be concluded that the assay is expected to be of practical applicability because of the results' relevance.

  13. Photography by Cameras Integrated in Smartphones as a Tool for Analytical Chemistry Represented by an Butyrylcholinesterase Activity Assay

    Directory of Open Access Journals (Sweden)

    Miroslav Pohanka

    2015-06-01

    Full Text Available Smartphones are popular devices frequently equipped with sensitive sensors and great computational ability. Despite the widespread availability of smartphones, practical uses in analytical chemistry are limited, though some papers have proposed promising applications. In the present paper, a smartphone is used as a tool for the determination of cholinesterasemia i.e., the determination of a biochemical marker butyrylcholinesterase (BChE. The work should demonstrate suitability of a smartphone-integrated camera for analytical purposes. Paper strips soaked with indoxylacetate were used for the determination of BChE activity, while the standard Ellman’s assay was used as a reference measurement. In the smartphone-based assay, BChE converted indoxylacetate to indigo blue and coloration was photographed using the phone’s integrated camera. A RGB color model was analyzed and color values for the individual color channels were determined. The assay was verified using plasma samples and samples containing pure BChE, and validated using Ellmans’s assay. The smartphone assay was proved to be reliable and applicable for routine diagnoses where BChE serves as a marker (liver function tests; some poisonings, etc.. It can be concluded that the assay is expected to be of practical applicability because of the results’ relevance.

  14. Discovery of Highly Selective and Nanomolar Carbamate-Based Butyrylcholinesterase Inhibitors by Rational Investigation into Their Inhibition Mode.

    Science.gov (United States)

    Sawatzky, Edgar; Wehle, Sarah; Kling, Beata; Wendrich, Jan; Bringmann, Gerhard; Sotriffer, Christoph A; Heilmann, Jörg; Decker, Michael

    2016-03-10

    Butyrylcholinesterase (BChE) is a promising target for the treatment of later stage cognitive decline in Alzheimer's disease. A set of pseudo-irreversible BChE inhibitors with high selectivity over hAChE was synthesized based on carbamates attached to tetrahydroquinazoline scaffolds with the 2-thiophenyl compound 2p as the most potent inhibitor of eqBChE (KC = 14.3 nM) and also of hBChE (KC = 19.7 nM). The inhibitors transfer the carbamate moiety onto the active site under release of the phenolic tetrahydroquinazoline scaffolds that themselves act as neuroprotectants. By combination of kinetic data with molecular docking studies, a plausible binding model was probed describing how the tetrahydroquinazoline scaffold guides the carbamate into a close position to the active site. The model explains the influence of the carrier scaffold onto the affinity of an inhibitor just before carbamate transfer. This strategy can be used to utilize the binding mode of other carbamate-based inhibitors.

  15. Acetylcholinesterase and Butyrylcholinesterase Inhibitory Activities of β-Carboline and Quinoline Alkaloids Derivatives from the Plants of Genus Peganum

    Directory of Open Access Journals (Sweden)

    Ting Zhao

    2013-01-01

    Full Text Available It was reported that the main chemical constituents in plants of genus Peganum were a serial of β-carboline and quinoline alkaloids. These alkaloids were quantitatively assessed for selective inhibitory activities on acetylcholinesterase (AChE and butyrylcholinesterase (BChE by in vitro Ellman method. The results indicated that harmane was the most potent selective AChE inhibitor with an IC50 of 7.11 ± 2.00 μM and AChE selectivity index (SI, IC50 of BChE/IC50 of AChE of 10.82. Vasicine was the most potent BChE inhibitor with feature of dual AChE/BChE inhibitory activity, with an IC50 versus AChE/BChE of 13.68 ± 1.25/2.60 ± 1.47 μM and AChE SI of 0.19. By analyzing and comparing the IC50 and SI of those chemicals, it was indicated that the β-carboline alkaloids displayed more potent AChE inhibition but less BChE inhibition than quinoline alkaloids. The substituent at the C7 position of the β-carboline alkaloids and C3 and C9 positions of quinoline alkaloids played a critical role in AChE or BChE inhibition. The potent inhibition suggested that those alkaloids may be used as candidates for treatment of Alzheimer’s disease. The analysis of the quantitative structure-activity relationship of those compounds investigated might provide guidance for the design and synthesis of AChE and BChE inhibitors.

  16. A novel mutation in the BCHE gene and phenotype identified in a child with low butyrylcholinesterase activity: a case report.

    Science.gov (United States)

    Yu, Rentao; Guo, Yanzhi; Dan, Yunjie; Tan, Wenting; Mao, Qing; Deng, Guohong

    2018-04-10

    Butyrylcholinesterase (BChE), an ester hydrolase produced mainly by the liver, hydrolyzes certain short-acting neuromuscular blocking agents, like succinylcholine and mivacurium that are widely used during anesthesia. Patients with BChE deficiency are possibly in danger of postanesthetic apnea. Hereditary BChE deficiency results from the mutations of BCHE gene located on chromosome 3, 3q26.1-q26.2, between nucleotides 165,490,692-165,555,260. This study describes a novel mutation in a child with BChE deficiency. In general, this child appeared healthy and well-developed with a normal appearance. However, the results of Wechsler Intelligence Scale showed that the full-scale intelligence quotient (FIQ) was 53, classified into the group with the minor defect. The BChE activity was 32.0 U/L, considerably lower than the normal lower limit (reference range: 5000-12,000 U/L). Sanger sequencing showed that there were 2 mutations in the exon 2 of BCHE gene of this child. One is a heterozygous mutation rs764588882 (NM_000055.3: c.401_402insA, p.Asn134Lysfs*23). The other one is a heterozygous mutation (NM_000055.3: c.73A > T, p.Lys25Ter) that has never been reported before. The two mutations lead to a premature stop of transcription. Double heterozygous recessive mutations are the cause of BChE deficiency of this boy in this study, including a novel mutation c.73A > T. Intellectual disability is a new phenotype that is probably associated with this mutation.

  17. Butyryl-cholinesterase is related to muscle mass and strength. A new biomarker to identify elderly subjects at risk of sarcopenia.

    Science.gov (United States)

    Cacciatore, Francesco; Della-Morte, David; Basile, Claudia; Curcio, Francesco; Liguori, Ilaria; Roselli, Mario; Gargiulo, Gaetano; Galizia, Gianluigi; Bonaduce, Domenico; Abete, Pasquale

    2015-01-01

    To determine the relationship between Butyryl-cholinesterase (α-glycoprotein synthesized in the liver, b-CHE) and muscle mass and strength. Muscle mass by bioimpedentiometer and muscle strength by grip strength were evaluated in 337 elderly subjects (mean age: 76.2 ± 6.7 years) admitted to comprehensive geriatric assessment. b-CHE levels were lower in sarcopenic than in nonsarcopenic elderly subjects (p elderly subjects. Thus, b-CHE may be considered to be a fair biomarker for identifying elderly subjects at risk of sarcopenia.

  18. Design, synthesis, biological evaluation and docking study of 5-oxo-4,5-dihydropyrano[3,2-c]chromene derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors.

    Science.gov (United States)

    Khoobi, Mehdi; Alipour, Masoumeh; Sakhteman, Amirhossein; Nadri, Hamid; Moradi, Alireza; Ghandi, Mehdi; Emami, Saeed; Foroumadi, Alireza; Shafiee, Abbas

    2013-10-01

    A series of fused coumarins namely 5-oxo-4,5-dihydropyrano[3,2-c]chromenes linked to N-benzylpyridinium scaffold were synthesized and evaluated as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. The 1-(4-fluorobenzyl)pyridinium derivative 6g showed the most potent anti-AChE activity (IC50 value=0.038 μM) and the highest AChE/BuChE selectivity (SI>48). The docking study permitted us to rationalize the observed structure-affinity relationships and to detect possible binding modes. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  19. Quantitation of ortho-cresyl phosphate adducts to butyrylcholinesterase in human serum by immunomagnetic-UHPLC-MS/MS

    NARCIS (Netherlands)

    Johnson, D.; Carter, M.D.; Crow, B.S.; Isenberg, S.L.; Graham, L.A.; Erol, H.A.; Watson, C.M.; Pantazides, B.G.; Schans, M.J. van der; Langenberg, J.P.; Noort, D.; Blake, T.A.; Thomas, J.D.; Johnson, R.C.

    2015-01-01

    Tri-ortho-cresyl phosphate (ToCP) is an anti-wear, flame retardant additive used in industrial lubricants, hydraulic fluids and gasoline. The neurotoxic effects of ToCP arise from the liver-activated metabolite 2-(o-cresyl)-4H-1,3,2-benzodioxaphosphoran-2-one (cresyl saligenin phosphate or CBDP),

  20. Effect of Pretreatment With Human Butyrylcholinesterase Scavengers on the Toxicokinetics and Binding of Nerve Agents in Guinea Pigs and Marmosets

    National Research Council Canada - National Science Library

    Langenberg, Jan

    2002-01-01

    ... of (+/-)-sarin in guinea pigs was studied. After i.m. administration of HuBuChE, the BuChE activity in blood gradually increased, reaching a maximum after 20-24 h, and remaining stable for about another 24 h...

  1. A step toward the reactivation of aged cholinesterases-crystal structure of ligands binding to aged human butyrylcholinesterase

    NARCIS (Netherlands)

    Wandhammer, M.; Koning, M. de; Grol, M. van; Loiodice, M.; Saurel, L.; Noort, D.; Goeldner, M.; Nachon, F.

    2013-01-01

    Organophosphorus nerve agents irreversibly inhibit cholinesterases. Phosphylation of the catalytic serine can be reversed by the mean of powerful nucleophiles like oximes. But the phosphyl adduct can undergo a rapid spontaneous reaction leading to an aged enzyme, i.e., a conjugated enzyme that is no

  2. Protection from pulmonary tissue damage associated with infection of cynomolgus macaques by highly pathogenic avian influenza virus (H5N1) by low dose natural human IFN-α administered to the buccal mucosa.

    Science.gov (United States)

    Strayer, David R; Carter, William A; Stouch, Bruce C; Stittelaar, Koert J; Thoolen, Robert J M M; Osterhaus, Albert D M E; Mitchell, William M

    2014-10-01

    Using an established nonhuman primate model for H5N1 highly pathogenic influenza virus infection in humans, we have been able to demonstrate the prophylactic mitigation of the pulmonary damage characteristic of human fatal cases from primary influenza virus pneumonia with a low dose oral formulation of a commercially available parenteral natural human interferon alpha (Alferon N Injection®). At the highest oral dose (62.5IU/kg body weight) used there was a marked reduction in the alveolar inflammatory response with minor evidence of alveolar and interstitial edema in contrast to the hemorrhage and inflammatory response observed in the alveoli of control animals. The mitigation of severe damage to the lower pulmonary airway was observed without a parallel reduction in viral titers. Clinical trial data will be necessary to establish its prophylactic human efficacy for highly pathogenic influenza viruses. Copyright © 2014. Published by Elsevier B.V.

  3. Computer-Administered Interviews and Rating Scales

    Science.gov (United States)

    Garb, Howard N.

    2007-01-01

    To evaluate the value of computer-administered interviews and rating scales, the following topics are reviewed in the present article: (a) strengths and weaknesses of structured and unstructured assessment instruments, (b) advantages and disadvantages of computer administration, and (c) the validity and utility of computer-administered interviews…

  4. Nurse-administered propofol sedation for endoscopy

    DEFF Research Database (Denmark)

    Jensen, J T; Vilmann, P; Horsted, T

    2011-01-01

    The aim of the present study was to perform a risk analysis during the implementation phase of nurse-administered propofol sedation (NAPS) and to validate our structured training program.......The aim of the present study was to perform a risk analysis during the implementation phase of nurse-administered propofol sedation (NAPS) and to validate our structured training program....

  5. Synthesis, structural characterization, docking, lipophilicity and cytotoxicity of 1-[(1R)-1-(6-fluoro-1,3-benzothiazol-2-yl)ethyl]-3-alkyl carbamates, novel acetylcholinesterase and butyrylcholinesterase pseudo-irreversible inhibitors

    Czech Academy of Sciences Publication Activity Database

    Pejchal, V.; Štěpánková, Š.; Pejchalová, M.; Královec, K.; Havelek, R.; Růžičková, Z.; Ajani, Haresh; Lo, Rabindranath; Lepšík, Martin

    2016-01-01

    Roč. 24, č. 7 (2016), s. 1560-1572 ISSN 0968-0896 R&D Projects: GA ČR GBP208/12/G016 Institutional support: RVO:61388963 Keywords : halogenated benzothiazole * carbamates * acetylcholinesterase * butyrylcholinesterase inhibition * pseudo-irreversible mechanism * covalent docking Subject RIV: CC - Organic Chemistry Impact factor: 2.930, year: 2016

  6. Clinical Pharmacokinetics of Systemically Administered Antileishmanial Drugs

    NARCIS (Netherlands)

    Kip, Anke E; Schellens, Jan H M; Beijnen, Jos H; Dorlo, Thomas P C

    This review describes the pharmacokinetic properties of the systemically administered antileishmanial drugs pentavalent antimony, paromomycin, pentamidine, miltefosine and amphotericin B (AMB), including their absorption, distribution, metabolism and excretion and potential drug-drug interactions.

  7. New derivatives of 3,4-dihydroisoquinoline-3-carboxylic acid with free-radical scavenging, D-amino acid oxidase, acetylcholinesterase and butyrylcholinesterase inhibitory activity.

    Science.gov (United States)

    Solecka, Jolanta; Guśpiel, Adam; Postek, Magdalena; Ziemska, Joanna; Kawęcki, Robert; Lęczycka, Katarzyna; Osior, Agnieszka; Pietrzak, Bartłomiej; Pypowski, Krzysztof; Wyrzykowska, Agata

    2014-09-30

    A series of 3,4-dihydroisoquinoline-3-carboxylic acid derivatives were synthesised and tested for their free-radical scavenging activity using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH·), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical (ABTS·+), superoxide anion radical (O2·-) and nitric oxide radical (·NO) assays. We also studied d-amino acid oxidase (DAAO), acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity. Almost each of newly synthesised compounds exhibited radical scavenging capabilities. Moreover, several compounds showed moderate inhibitory activities against DAAO, AChE and BuChE. Compounds with significant free-radical scavenging activity may be potential candidates for therapeutics used in oxidative-stress-related diseases.

  8. Aspirin Hydrolysis in Plasma Is a Variable Function of Butyrylcholinesterase and Platelet-activating Factor Acetylhydrolase 1b2 (PAFAH1b2)*

    Science.gov (United States)

    Zhou, Gang; Marathe, Gopal K.; Hartiala, Jaana; Hazen, Stanley L.; Allayee, Hooman; Tang, W. H. Wilson; McIntyre, Thomas M.

    2013-01-01

    Aspirin is rapidly hydrolyzed within erythrocytes by a heterodimer of PAFAH1b2/PAFAH1b3 but also in plasma by an unidentified activity. Hydrolysis in both compartments was variable, with a 12-fold variation in plasma among 2226 Cleveland Clinic GeneBank patients. Platelet inhibition by aspirin was suppressed in plasma that rapidly hydrolyzed aspirin. Plasma aspirin hydrolysis was significantly higher in patients with coronary artery disease compared with control subjects (16.5 ± 4.4 versus 15.1 ± 3.7 nmol/ml/min; p = 3.4 × 10−8). A genome-wide association study of 2054 GeneBank subjects identified a single locus immediately adjacent to the BCHE (butyrylcholinesterase) gene associated with plasma aspirin hydrolytic activity (lead SNP, rs6445035; p = 9.1 × 10−17). However, its penetrance was low, and plasma from an individual with an inactivating mutation in BCHE still effectively hydrolyzed aspirin. A second aspirin hydrolase was identified in plasma, the purification of which showed it to be homomeric PAFAH1b2. This is distinct from the erythrocyte PAFAH1b2/PAFAH1b3 heterodimer. Inhibitors showed that both butyrylcholinesterase (BChE) and PAFAH1b2 contribute to aspirin hydrolysis in plasma, with variation primarily reflecting non-genetic variation of BChE activity. Therefore, aspirin is hydrolyzed in plasma by two enzymes, BChE and a new extracellular form of platelet-activating factor acetylhydrolase, PAFAH1b2. Hydrolytic effectiveness varies widely primarily from non-genetic variation of BChE activity that affects aspirin bioavailability in blood and the ability of aspirin to inhibit platelet aggregation. PMID:23508960

  9. Aspirin hydrolysis in plasma is a variable function of butyrylcholinesterase and platelet-activating factor acetylhydrolase 1b2 (PAFAH1b2).

    Science.gov (United States)

    Zhou, Gang; Marathe, Gopal K; Hartiala, Jaana; Hazen, Stanley L; Allayee, Hooman; Tang, W H Wilson; McIntyre, Thomas M

    2013-04-26

    Aspirin is rapidly hydrolyzed within erythrocytes by a heterodimer of PAFAH1b2/PAFAH1b3 but also in plasma by an unidentified activity. Hydrolysis in both compartments was variable, with a 12-fold variation in plasma among 2226 Cleveland Clinic GeneBank patients. Platelet inhibition by aspirin was suppressed in plasma that rapidly hydrolyzed aspirin. Plasma aspirin hydrolysis was significantly higher in patients with coronary artery disease compared with control subjects (16.5 ± 4.4 versus 15.1 ± 3.7 nmol/ml/min; p = 3.4 × 10(-8)). A genome-wide association study of 2054 GeneBank subjects identified a single locus immediately adjacent to the BCHE (butyrylcholinesterase) gene associated with plasma aspirin hydrolytic activity (lead SNP, rs6445035; p = 9.1 × 10(-17)). However, its penetrance was low, and plasma from an individual with an inactivating mutation in BCHE still effectively hydrolyzed aspirin. A second aspirin hydrolase was identified in plasma, the purification of which showed it to be homomeric PAFAH1b2. This is distinct from the erythrocyte PAFAH1b2/PAFAH1b3 heterodimer. Inhibitors showed that both butyrylcholinesterase (BChE) and PAFAH1b2 contribute to aspirin hydrolysis in plasma, with variation primarily reflecting non-genetic variation of BChE activity. Therefore, aspirin is hydrolyzed in plasma by two enzymes, BChE and a new extracellular form of platelet-activating factor acetylhydrolase, PAFAH1b2. Hydrolytic effectiveness varies widely primarily from non-genetic variation of BChE activity that affects aspirin bioavailability in blood and the ability of aspirin to inhibit platelet aggregation.

  10. Training pharmacy technicians to administer immunizations.

    Science.gov (United States)

    McKeirnan, Kimberly C; Frazier, Kyle R; Nguyen, Maryann; MacLean, Linda Garrelts

    To evaluate the effectiveness of an immunization training program for pharmacy technicians on technicians' self-reported confidence, knowledge, and number of vaccines administered. A one-group pre- and posttest study was conducted with certified pharmacy technicians from Albertsons and Safeway community pharmacies in Idaho. Thirty pharmacy technicians were recruited to participate in an immunization administration training program comprising a 2-hour home study and a 2-hour live training. Pharmacy technician scores on a 10-question knowledge assessment, responses on a pre- and posttraining survey, and number of immunizations administered in the 6-month period following the training were collected. Twenty-five pharmacy technicians completed the home study and live portions of the immunization training program. All 29 pharmacy technicians who took the home study assessment passed with greater than 70% competency on the first attempt. Technicians self-reported increased confidence with immunization skills between the pretraining survey and the posttraining survey. From December 2016 to May 2017, the technicians administered 953 immunizations with 0 adverse events reported. For the first time, pharmacy technicians have legally administered immunizations in the United States. Trained pharmacy technicians demonstrated knowledge of vaccination procedures and self-reported improved confidence in immunization skills and administered immunizations after participating in a 4-hour training program. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  11. Pharmacokinetics of orally administered tramadol in domestic rabbits (Oryctolagus cuniculus).

    Science.gov (United States)

    Souza, Marcy J; Greenacre, Cheryl B; Cox, Sherry K

    2008-08-01

    To determine the pharmacokinetics of an orally administered dose of tramadol in domestic rabbits (Oryctolagus cuniculus). 6 healthy adult sexually intact female New Zealand White rabbits. Physical examinations and plasma biochemical analyses were performed to ensure rabbits were healthy prior to the experiment. Rabbits were anesthetized with isoflurane, and IV catheters were placed in a medial saphenous or jugular vein for collection of blood samples. One blood sample was collected before treatment with tramadol. Rabbits were allowed to recover from anesthesia a minimum of 1 hour before treatment. Then, tramadol (11 mg/kg, PO) was administered once, and blood samples were collected at various time points up to 360 minutes after administration. Blood samples were analyzed with high-performance liquid chromatography to determine plasma concentrations of tramadol and its major metabolite (O-desmethyltramadol). No adverse effects were detected after oral administration of tramadol to rabbits. Mean +/- SD half-life of tramadol after administration was 145.4 +/- 81.0 minutes; mean +/- SD maximum plasma concentration was 135.3 +/- 89.1 ng/mL. Although the dose of tramadol required to provide analgesia in rabbits is unknown, the dose administered in the study reported here did not reach a plasma concentration of tramadol or O-desmethyltramadol that would provide sufficient analgesia in humans for clinically acceptable periods. Many factors may influence absorption of orally administered tramadol in rabbits.

  12. Human Abuse Potential of an Abuse-Deterrent (AD), Extended-Release (ER) Morphine Product Candidate (Morphine-ADER Injection-Molded Tablets) vs Extended-Release Morphine Administered Intranasally in Nondependent Recreational Opioid Users.

    Science.gov (United States)

    Webster, Lynn R; Smith, Michael D; Lawler, John; Lindhardt, Karsten; Dayno, Jeffrey M

    2017-09-01

    To compare the relative human abuse potential after insufflation of manipulated morphine abuse-deterrent, extended-release injection-molded tablets (morphine-ADER-IMT) with that of marketed morphine ER tablets. A randomized, double-blind, double-dummy, active- and placebo-controlled five-way crossover study was performed with adult volunteers who were experienced, nondependent, recreational opioid users. After intranasal (IN) administration of manipulated high-volume (HV) morphine-ADER-IMT (60 mg), participants were randomized (1:1:1:1) to receive IN manipulated low-volume (LV) morphine ER (60 mg), IN manipulated LV morphine-ADER-IMT, intact oral morphine-ADER-IMT (60 mg), and placebo in crossover fashion. Pharmacodynamic and pharmacokinetic assessments included peak effect of drug liking (E max ; primary endpoint) using drug liking visual analog scale (VAS) score, E max using overall drug liking, and take drug again (TDA) VASs scores, and mean abuse quotient (AQ), a pharmacokinetic parameter associated with drug liking. Forty-six participants completed the study. After insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT, drug liking E max was significantly lower ( P  <   0.0001) compared with IN morphine ER. Overall drug liking and TDA E max values were significantly lower ( P  <   0.0001) after insufflation of HV morphine-ADER-IMT and LV morphine-ADER-IMT compared with IN morphine ER. Mean AQ was lower after insufflation of HV (9.2) and LV (2.3) morphine-ADER-IMT or ingestion of oral morphine-ADER-IMT (5.5) compared with insufflation of LV morphine ER (37.2). All drug liking, take drug again, and abuse quotient endpoints support a significantly lower abuse potential with insufflation of manipulated morphine-ADER-IMT compared with manipulated and insufflated non-AD ER morphine. © 2016 American Academy of Pain Medicine.

  13. Training and experience of doctors administering obstetric ...

    African Journals Online (AJOL)

    Background All the published Saving Mothers Reports generated by the National Committee of the Confidential Enquiries into Maternal Deaths in South Africa have associated anaesthesia-related maternal deaths with the lack of skills of the doctors administering the anaesthesia. The Reports have shown the Free State to ...

  14. Synthesis of Selective Butyrylcholinesterase Inhibitors Coupled between α-Lipoic Acid and Polyphenols by Using 2-(Piperazin-1-yl)ethanol Linker

    Energy Technology Data Exchange (ETDEWEB)

    Yeun, Go Heun; Lee, Seung Hwan; LIm, Yong Bae; Lee, Hye Sook; Lee, Bong Ho; Park, Jeong Ho [Hanbat National Univ., Daejeon (Korea, Republic of); Won, Mooho [Kangwon National Univ., Chuncheon (Korea, Republic of)

    2013-04-15

    In the previous paper (Bull. Korean Chem. Soc., 2011, 32, 2997), the hybrid molecules between α-lipoic acid (ALA) and polyphenols (PPs) connected with neutral 2-(2-aminoethoxy)ethanol linker (linker-1) showed new biological activity such as butyrylcholinesterase (BuChE) inhibition. In order to increase the binding affinity of the hybrid compounds to cholinesterase (ChE), the neutral 2-(2-aminoethoxy)ethanol (linker 1) was switched to the cationic 2-(piperazin-1-yl)ethanol linker (linker 2). The IC{sub 50} values of the linker-2 hybrid molecules for BuChE inhibition were lower than those of linker-1 hybrid molecules (except 9-2) and they also had the same great selectivity for BuChE over AChE (> 800 fold) as linker-1 hybrid molecules. ALA-acetyl caffeic acid (10-2, ALA-AcCA) was shown as an effective inhibitor of BuChE (IC{sub 50} = 0.44 ± 0.24 μM). A kinetic study using 7-2 showed that it is the same mixed type inhibition as 7-1. Its inhibition constant (Ki) to BuChE is 4.3 ± 0.09 μM.

  15. Synthesis of Selective Butyrylcholinesterase Inhibitors Coupled between α-Lipoic Acid and Polyphenols by Using 2-(Piperazin-1-yl)ethanol Linker

    International Nuclear Information System (INIS)

    Yeun, Go Heun; Lee, Seung Hwan; LIm, Yong Bae; Lee, Hye Sook; Lee, Bong Ho; Park, Jeong Ho; Won, Mooho

    2013-01-01

    In the previous paper (Bull. Korean Chem. Soc., 2011, 32, 2997), the hybrid molecules between α-lipoic acid (ALA) and polyphenols (PPs) connected with neutral 2-(2-aminoethoxy)ethanol linker (linker-1) showed new biological activity such as butyrylcholinesterase (BuChE) inhibition. In order to increase the binding affinity of the hybrid compounds to cholinesterase (ChE), the neutral 2-(2-aminoethoxy)ethanol (linker 1) was switched to the cationic 2-(piperazin-1-yl)ethanol linker (linker 2). The IC 50 values of the linker-2 hybrid molecules for BuChE inhibition were lower than those of linker-1 hybrid molecules (except 9-2) and they also had the same great selectivity for BuChE over AChE (> 800 fold) as linker-1 hybrid molecules. ALA-acetyl caffeic acid (10-2, ALA-AcCA) was shown as an effective inhibitor of BuChE (IC 50 = 0.44 ± 0.24 μM). A kinetic study using 7-2 showed that it is the same mixed type inhibition as 7-1. Its inhibition constant (Ki) to BuChE is 4.3 ± 0.09 μM

  16. Butyrylcholinesterase (BChE) activity is associated with the risk of preeclampsia: influence on lipid and lipoprotein metabolism and oxidative stress.

    Science.gov (United States)

    Rahimi, Zohreh; Ahmadi, Reza; Vaisi-Raygani, Asad; Rahimi, Ziba; Bahrehmand, Fariborz; Parsian, Abbas

    2013-11-01

    To determine the butyrylcholinesterase (BChE) activity and phenotypes in preeclampsia and its possible association with lipid and lipoprotein metabolism and oxidative stress in preeclamptic women. In a case-control study, 101 pregnant women with normal pregnancy and 198 women with preeclampsia from Western Iran were studied. The serum BChE activity and phenotypes were measured using spectrophotometric method. The apolipoprotein E (APOE) genotypes were identified using PCR-RFLP. The serum malondialdehyde (MDA) level and total antioxidant capacity (TAC) were determined by HPLC and commercial kits, respectively. The BChE activity and the frequency of non-usual BChE phenotype in preeclamptic women were significantly lower and higher, respectively compared to controls. There was a higher BChE activity in the presence of APOE ε3ε4 compared to ε3ε3 genotype in preeclamptic women. In addition, there were significant positive correlations between BChE activity and the levels of low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, total cholesterol (TC) and TAC. However, there was a negative but significant correlation between BChE activity and MDA level. Our study for the first time indicated that BChE activity might be involved in the pathogenesis of preeclampsia through influence on lipid and lipoprotein metabolism and oxidative stress.

  17. Nurse-administered propofol sedation for endoscopy

    DEFF Research Database (Denmark)

    Jensen, J T; Vilmann, P; Horsted, T

    2011-01-01

    BACKGROUND AND STUDY AIMS: The aim of the present study was to perform a risk analysis during the implementation phase of nurse-administered propofol sedation (NAPS) and to validate our structured training program. PATIENTS AND METHODS: A structured training program was developed both for endosco......BACKGROUND AND STUDY AIMS: The aim of the present study was to perform a risk analysis during the implementation phase of nurse-administered propofol sedation (NAPS) and to validate our structured training program. PATIENTS AND METHODS: A structured training program was developed both...... pressure was recorded in 451 patients (26%). Independent risk factors were type of intervention and level of experience of the staff performing the sedation. CONCLUSION: These results were obtained after development of a structured training program both for endoscopists and nurses using propofol...... for sedation, and can be used as basis for further comparison. NAPS for endoscopic procedures is safe when performed by personnel properly trained in airway handling and sedation with propofol, and has considerable advantages compared with conventional sedation for endoscopy....

  18. Tumour targeting with systemically administered bacteria.

    LENUS (Irish Health Repository)

    Morrissey, David

    2012-01-31

    Challenges for oncology practitioners and researchers include specific treatment and detection of tumours. The ideal anti-cancer therapy would selectively eradicate tumour cells, whilst minimising side effects to normal tissue. Bacteria have emerged as biological gene vectors with natural tumour specificity, capable of homing to tumours and replicating locally to high levels when systemically administered. This property enables targeting of both the primary tumour and secondary metastases. In the case of invasive pathogenic species, this targeting strategy can be used to deliver genes intracellularly for tumour cell expression, while non-invasive species transformed with plasmids suitable for bacterial expression of heterologous genes can secrete therapeutic proteins locally within the tumour environment (cell therapy approach). Many bacterial genera have been demonstrated to localise to and replicate to high levels within tumour tissue when intravenously (IV) administered in rodent models and reporter gene tagging of bacteria has permitted real-time visualisation of this phenomenon. Live imaging of tumour colonising bacteria also presents diagnostic potential for this approach. The nature of tumour selective bacterial colonisation appears to be tumour origin- and bacterial species- independent. While originally a correlation was drawn between anaerobic bacterial colonisation and the hypoxic nature of solid tumours, it is recently becoming apparent that other elements of the unique microenvironment within solid tumours, including aberrant neovasculature and local immune suppression, may be responsible. Here, we consider the pre-clinical data supporting the use of bacteria as a tumour-targeting tool, recent advances in the area, and future work required to develop it into a beneficial clinical tool.

  19. Recombinant butyryl-cholinesterase (RBuChe) therapy following VX poisoning by the percutaneous route: preliminary studies

    International Nuclear Information System (INIS)

    Speakman, P.; Armstrong, S.

    2009-01-01

    Medical countermeasures to prevent or mitigate the effects of nerve agent poisoning are part of the UK MoD's integrated approach to CBRN defence. Protexia is currently in advanced development as a pretreatment for nerve agent poisoning by PharmAthene in collaboration with US DoD. The principle of its use in this context has been demonstrated in a model of inhalation exposure. Nerve agent poisoning by the percutaneous route poses additional challenges for medical countermeasures. The present study investigates the effects of non-pegylated rBuChE administered following poisoning by VX in an animal model of percutaneous exposure. This investigation is part of an ongoing programme of work assessing the potential of candidate medical interventions. Male guinea pigs implanted with dermal and blood microdialysis probes were maintained under anaesthesia. VX (296 micro g/kg or 740 micro g/kg) was applied to the dorsal skin and non-pegylated rBuChE or placebo was administered (i.v.) 30 minutes later. Dialysate fractions were collected for 8 hours and VX was analysed by LC-MS-MS. Cholinesterase levels were measured in selected tissues post mortem. Following VX (296 micro g/kg), non-pegylated rBuChE significantly reduced the concentration of VX in the blood but had no effect on dermal concentrations; additionally following VX (740 micro g/kg), non-pegylated rBuChE prevented lethality. Tissue cholinesterase activity was inhibited following VX exposure but in those animals treated with rhBuChE, activities were similar to control values. To our knowledge these results provide the first evidence of the mechanism of therapeutic intervention with rBuChE. Further work is necessary to increase confidence in these preliminary observations by conducting confirmatory studies. Crown Copyright 2008. This work was carried out as part of the UK MoD NBC Research Programme. Non-pegylated rBuChE was supplied by PharmAthene under a materials transfer and non-disclosure agreement. (author)

  20. Rivastigmine: the advantages of dual inhibition of acetylcholinesterase and butyrylcholinesterase and its role in subcortical vascular dementia and Parkinson’s disease dementia

    Directory of Open Access Journals (Sweden)

    Kandiah N

    2017-04-01

    Full Text Available Nagaendran Kandiah,1,2 Ming-Chyi Pai,3,4 Vorapun Senanarong,5 Irene Looi,6,7 Encarnita Ampil,8 Kyung Won Park,9 Ananda Krishna Karanam,10 Stephen Christopher11 1Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, 2Duke-NUS, Graduate Medical School, Singapore; 3Division of Behavioral Neurology, Department of Neurology, 4Alzheimer’s Disease Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan; 5Division of Neurology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 6Clinical Research Centre, 7Department of Medicine, Hospital Seberang Jaya, Penang, Malaysia; 8Department of Neurology and Psychiatry, Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines; 9Department of Neurology and Cognitive Disorders and Dementia Center, Institute of Convergence Bio-Health, Dong-A University College of Medicine, Busan, Republic of Korea; 10Novartis Healthcare Private Limited, Hyderabad, India; 11Novartis (Singapore Pte. Ltd., Singapore Abstract: Several studies have demonstrated clinical benefits of sustained cholinesterase inhibition with rivastigmine in Alzheimer’s disease (AD and Parkinson’s disease dementia (PDD. Unlike donepezil and galantamine that selectively inhibit acetylcholinesterase (AChE; EC 3.1.1.7, rivastigmine is a unique cholinesterase inhibitor with both AChE and butyrylcholinesterase (BuChE; EC 3.1.1.8 inhibitory activity. Rivastigmine is also available as transdermal patch that has been approved by the US Food and Drug Administration for the treatment of mild, moderate, and severe AD as well as mild-to-moderate PDD. In this review, we explore the role of BuChE inhibition in addition to AChE inhibition with rivastigmine in the outcomes of cognition, global function, behavioral symptoms, and activities of daily living. Additionally, we review the evidence supporting the use of dual

  1. Evaluation of Novel Dual Acetyl- and Butyrylcholinesterase Inhibitors as Potential Anti-Alzheimer’s Disease Agents Using Pharmacophore, 3D-QSAR, and Molecular Docking Approaches

    Directory of Open Access Journals (Sweden)

    Xiaocong Pang

    2017-07-01

    Full Text Available DL0410, containing biphenyl and piperidine skeletons, was identified as an acetylcholinesterase (AChE and butyrylcholinesterase (BuChE inhibitor through high-throughput screening assays, and further studies affirmed its efficacy and safety for Alzheimer’s disease treatment. In our study, a series of novel DL0410 derivatives were evaluated for inhibitory activities towards AChE and BuChE. Among these derivatives, compounds 6-1 and 7-6 showed stronger AChE and BuChE inhibitory activities than DL0410. Then, pharmacophore modeling and three-dimensional quantitative structure activity relationship (3D-QSAR models were performed. The R2 of AChE and BuChE 3D-QSAR models for training set were found to be 0.925 and 0.883, while that of the test set were 0.850 and 0.881, respectively. Next, molecular docking methods were utilized to explore the putative binding modes. Compounds 6-1 and 7-6 could interact with the amino acid residues in the catalytic anionic site (CAS and peripheral anionic site (PAS of AChE/BuChE, which was similar with DL0410. Kinetics studies also suggested that the three compounds were all mixed-types of inhibitors. In addition, compound 6-1 showed better absorption and blood brain barrier permeability. These studies provide better insight into the inhibitory behaviors of DL0410 derivatives, which is beneficial for rational design of AChE and BuChE inhibitors in the future.

  2. Orally administered nicotine induces urothelial hyperplasia in rats and mice

    International Nuclear Information System (INIS)

    Dodmane, Puttappa R.; Arnold, Lora L.; Pennington, Karen L.; Cohen, Samuel M.

    2014-01-01

    Highlights: • Rats and mice orally administered with nicotine tartrate for total of 4 weeks. • No treatment-related death or whole body toxicity observed in any of the groups. • Urothelium showed simple hyperplasia in treated rats and mice. • No significant change in BrdU labeling index or SEM classification of urothelium. - Abstract: Tobacco smoking is a major risk factor for multiple human cancers including urinary bladder carcinoma. Tobacco smoke is a complex mixture containing chemicals that are known carcinogens in humans and/or animals. Aromatic amines a major class of DNA-reactive carcinogens in cigarette smoke, are not present at sufficiently high levels to fully explain the incidence of bladder cancer in cigarette smokers. Other agents in tobacco smoke could be excreted in urine and enhance the carcinogenic process by increasing urothelial cell proliferation. Nicotine is one such major component, as it has been shown to induce cell proliferation in multiple cell types in vitro. However, in vivo evidence specifically for the urothelium is lacking. We previously showed that cigarette smoke induces increased urothelial cell proliferation in mice. In the present study, urothelial proliferative and cytotoxic effects were examined after nicotine treatment in mice and rats. Nicotine hydrogen tartrate was administered in drinking water to rats (52 ppm nicotine) and mice (514 ppm nicotine) for 4 weeks and urothelial changes were evaluated. Histopathologically, 7/10 rats and 4/10 mice showed simple hyperplasia following nicotine treatment compared to none in the controls. Rats had an increased mean BrdU labeling index compared to controls, although it was not statistically significantly elevated in either species. Scanning electron microscopic visualization of the urothelium did not reveal significant cytotoxicity. These findings suggest that oral nicotine administration induced urothelial hyperplasia (increased cell proliferation), possibly due to a

  3. Design, synthesis, docking study and biological evaluation of some novel tetrahydrochromeno [3',4':5,6]pyrano[2,3-b]quinolin-6(7H)-one derivatives against acetyl- and butyrylcholinesterase.

    Science.gov (United States)

    Khoobi, Mehdi; Alipour, Masoumeh; Moradi, Alireza; Sakhteman, Amirhossein; Nadri, Hamid; Razavi, Seyyede Faeze; Ghandi, Mehdi; Foroumadi, Alireza; Shafiee, Abbas

    2013-10-01

    Novel hybrid derivatives of two known scaffolds; tetrahydroaminoquinoline and coumarin were synthesized and evaluated for both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities. By means of an efficient nanocatalyst, the reaction time for the syntheses of the target compounds was reduced. Subsequently, Ellman's modified method was used to evaluate the enzyme inhibitory activity of the synthesized structures. It was observed that most hybrid structures were moderate to potent inhibitors of AChE compared to Tacrine as the reference drug among which 7f with 4-fluorophenyl substituent was the most active compound (IC50=5 nM). Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  4. 32 CFR 637.11 - Authority to administer oaths.

    Science.gov (United States)

    2010-07-01

    ... ENFORCEMENT AND CRIMINAL INVESTIGATIONS MILITARY POLICE INVESTIGATION Investigations § 637.11 Authority to... administer oaths to military personnel who are subject to the UCMJ. The authority to administer oaths to...

  5. Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

    Science.gov (United States)

    Li, Bin; Eyer, Peter; Eddleston, Michael; Jiang, Wei; Schopfer, Lawrence M.; Lockridge, Oksana

    2013-01-01

    Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5 days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos. PMID:23566956

  6. Differential effects of developmental hypo- and hyperthyroidism on acetylcholinesterase and butyrylcholinesterase activity in the spinal cord of developing postnatal rat pups.

    Science.gov (United States)

    Koohestani, Faezeh; Brown, Chester M; Meisami, Esmail

    2012-11-01

    The plasticity and vulnerability of the rat spinal cord (SC) during postnatal development has been less investigated compared to other CNS structures. In this study, we determined the effects of thyroid hormonal (TH) deficiency and excess on postnatal growth and neurochemical development of the rat SC. The growth as well as the specific and total activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes of the SC were determined in hypo- and hyperthyroid rat pups at postnatal (P) days P1, P5, P10 and P21 (weaning), and were compared to age-matched untreated normal controls. AChE is a cholinergic synaptic enzyme while BuChE is a metabolic enzyme mainly found in glial cells and neurovascular cells. The SC is rich in somatic motor, autonomic cholinergic neurons and associated interneurons. Daily subcutaneous injection of pups with thyroxine (T4) and administration of antithyroid goitrogen propylthiouracil (PTU) in the litter's drinking water were used to induce hyper- and hypothyroidism, respectively. Enzyme assays were carried out spectrophotometrically at the above-mentioned ages, using SC homogenates with acetylthiocholine-chloride as the substrate, together with specific cholinesterase inhibitors, which specifically target AChE and BuChE. SC weights were significantly lower at P10 and P21 in hypothyroid pups but unchanged in the hyperthyroid ones. Hypothyroidism significantly reduced both specific and total AChE activity in SC of P10 and P21 rat pups, while having no effects on the BuChE activity, although total BuChE activity was decreased due to reduced total tissue weight. In contrast both specific and total AChE activities were markedly and significantly increased (>100%) in the P10 and P21 hyperthyroid pups. However, BuChE specific activity was unaffected by this treatment. The results indicate that hypothyroid condition significantly reduces, while hyperthyroidism increases, the postnatal development of cholinergic synapses, thereby

  7. Effectiveness of highly active antiretroviral therapy administered by general practitioners in rural South Africa

    NARCIS (Netherlands)

    Barth, R. E.; van der Meer, J. T. M.; Hoepelman, A. I. M.; Schrooders, P. A.; van de Vijver, D. A.; Geelen, S. P. M.; Tempelman, H. A.

    2008-01-01

    The purpose of this study was to assess the one-year efficacy of highly active antiretroviral therapy (HAART) administered by general practitioners in a primary care community clinic in rural South Africa. We performed an observational cohort study of 675 treatment-naive human immunodeficiency virus

  8. 32 CFR 644.396 - Assignment of personnel to administer.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Assignment of personnel to administer. 644.396... PROPERTY REAL ESTATE HANDBOOK Disposal Predisposal Action § 644.396 Assignment of personnel to administer... responsible representative to each installation, or group of installations, to act under his staff supervision...

  9. 8 CFR 337.8 - Oath administered by the courts.

    Science.gov (United States)

    2010-01-01

    ... Form N-646, that the applicant has been determined by the Attorney General to be eligible for admission... ALLEGIANCE § 337.8 Oath administered by the courts. (a) Notification of election. An applicant for... election to have the oath of allegiance administered in an appropriate court having jurisdiction over the...

  10. Statistical analysis of Japanese Thorotrast-administered autopsy cases--1980

    Energy Technology Data Exchange (ETDEWEB)

    Mori, T. (National Inst. of Radiological Sciences, Anagawa, Japan); Kato, Y.; Aoki, N.; Hatakeyama, S.

    1983-01-01

    In 193 cases autopsied between 1945 and 1980, all persons who had been intravascularly injected with Thorotrast in life, the authors found 131 malignant hepatic tumors, 20 liver cirrhoses, 6 myeloid leukemias, 4 erythroleukemias, 5 aplastic anemias, 4 lung cancers, 1 mesothelioma and 1 osteosarcoma. The causes of death in the Thorotrast-administered autopsy group (193 cases) were compared with those of a non-Thorotrast-administered autopsy group (95,000 cases) of the same sex and age at death as recorded in the Annals of Japanese Pathological Autopsy cases from 1958 to 1978. This comparison revealed that the frequencies of malignant hepatic tumors, liver cirrhosis, erythroleukemia, and aplastic anemia were significantly higher in the Thorotrast-administered group than in the non-Thorotrast-administered group.

  11. 47 CFR 97.509 - Administering VE requirements.

    Science.gov (United States)

    2010-10-01

    ..., grandchildren, stepchildren, parents, grandparents, stepparents, brothers, sisters, stepbrothers, stepsisters... accommodate an examinee whose physical disabilities require a special examination procedure. The administering VEs may require a physician's certification indicating the nature of the disability before determining...

  12. Findings from Survey Administered to Weatherization Training Centers

    Energy Technology Data Exchange (ETDEWEB)

    Conlon, Brian [Univ. of Tennessee, Knoxville, TN (United States); Tonn, Bruce Edward [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-03-01

    This report summarizes results of a survey administered to directors of weatherization training centers that receive funding from the U.S. Department of Energy. The survey presents results related to questions on training offered and future plans.

  13. The administered activity of radionuclides in nuclear medicine

    International Nuclear Information System (INIS)

    Nakamura, Mototoshi; Koga, Sukehiko; Kondo, Takeshi

    1993-01-01

    A survey of 104 hospitals was conducted to determine the administered activity of radionuclides. Eighty-five hospitals responded, and reported a total of 119,614 examinations in one year. The examinations included: bone scintigraphy, 26.4%; thallium-201 ( 201 Tl) myocardial scintigraphy, 15.5%; gallium-67 ( 67 Ga) scintigraphy, 13.3%; N-isopropyl-p-[ 123 I] iodoamphetamine (IMP) brain perfusion scintigraphy, 7.0%. The administered activity was corrected by body weight only for children at more than 80% of the responding hospitals. The number of hospitals that reported over-administration of radionuclide varied according to the type of scintigraphy performed: bone, 76%; inflammatory ( 67 Ga), 93%; myocardial ( 201 Tl), 89.2%; brain (IMP), 8.5%. The administered activity of IMP was closer to the upper limits specified in the Recommendations on Standardization of Radionuclide Imaging by the Japan Radioisotope Association (1987), because IMP is very expensive and is supplied as single vials. The highest average effective dose was for myocardial scintigraphy, the second-highest for inflammatory scintigraphy, and the third-highest for bone scintigraphy. In 201 Tl and 67 Ga scintigraphy, the entire contents of the vial may be administered two days before the expiration date, because the ratio of (true patient administered activity) to (declared patient administered activity) is similar to the ratio of (radioactivity on the day of supply) to (radioactivity on the day of expiration). The factors that influence administered activity are through put, price of the radionuclide, and whether the radionuclide is sold as a single vial. In order to decrease the effective dose, it is necessary to establish a close cooperation between medical personnel, the makers of radiopharmaceuticals, and manufactures of gamma cameras. (author)

  14. Informationally administered reward enhances intrinsic motivation in schizophrenia.

    Science.gov (United States)

    Lee, Hyeon-Seung; Jang, Seon-Kyeong; Lee, Ga-Young; Park, Seon-Cheol; Medalia, Alice; Choi, Kee-Hong

    2017-10-01

    Even when individuals with schizophrenia have an intact ability to enjoy rewarding moments, the means to assist them to translate rewarding experiences into goal-directed behaviors is unclear. The present study sought to determine whether informationally administered rewards enhance intrinsic motivation to foster goal-directed behaviors in individuals with schizophrenia (SZ) and healthy controls (HCs). Eighty-four participants (SZ=43, HCs=41) were randomly assigned to conditions involving either a performance-contingent reward with an informationally administered reward or a task-contingent reward with no feedback. Participants were asked to play two cognitive games of equalized difficulty. Accuracy, self-reported intrinsic motivation, free-choice intrinsic motivation (i.e., game play during a free-choice observation period), and perceived competency were measured. Intrinsic motivation and perceived competency in the cognitive games were similar between the two participant groups. The informationally administered reward significantly enhanced self-reported intrinsic motivation and perceived competency in both the groups. The likelihood that individuals with schizophrenia would play the game during the free-choice observation period was four times greater in the informationally administered reward condition than that in the no-feedback condition. Our findings suggest that, in the context of cognitive remediation, individuals with schizophrenia would benefit from informationally administered rewards. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Even 'safe' medications need to be administered with care.

    Science.gov (United States)

    Lutwak, Nancy; Howland, Mary Ann; Gambetta, Rosemarie; Dill, Curt

    2013-01-02

    A 60-year-old man with a history of hepatic cirrhosis and cardiomyopathy underwent transoesophageal echocardiogram. He received mild sedation and topical lidocaine. During the recovery period the patient developed ataxia and diplopia for about 30 mins, a result of lidocaine toxicity. The patient was administered a commonly used local anaesthetic, a combination of 2% viscous lidocaine, 4% lidocaine gargle and 5% lidocaine ointment topically to the oropharnyx. The total dose was at least 280 mg. Oral lidocaine undergoes extensive first pass metabolism and its clearance is quite dependent on rates of liver blood flow as well as other factors. The patient's central nervous system symptoms were mild and transient but remind us that to avoid adverse side effects, orally administered drugs with fairly high hepatic extraction ratio given to patients with chronic liver disease need to be given in reduced dosages. Even 'Safe' medications need to be carefully administered.

  16. [Preoperatively administered flomoxef sodium concentration in aqueous humor].

    Science.gov (United States)

    Miyamoto, Mariko; Watanabe, Yoichiro; Mizuki, Nobuhisa

    2007-04-01

    We intravenously administered flomoxef sodium (FMOX) 0.5-3.5 hours before cataract surgery and measured the concentration of the agent in the aqueous humor to investigate its penetration into the aqueous humor and its efficacy in the prevention of postoperative endophthalmitis. 56 patients who underwent cataract surgery were enrolled in this study. They received 1 g FMOX via a 20-minute intravenous drip beginning 0.5-3.5 hours before the operation. Aqueous humor was aspirated from the anterior chamber and assayed for FMOX concentration using high-performance liquid chromatography. The mean intraoperative FMOX concentrations in the patients' aqueous humor were 0.79 +/- 0.24 microg/ml (administered 3.5 hours before surgery)--1.47 0.79 microg/ml (administered 1.5 hours before surgery). These concentrations administered 0.5-3.0 hours before surgery sufficiently exceeded the minimum inhibitory concentration (MIC) 90 values against Staphylococcus epidermidis, Staphylococcus aureus and Propionibacterium acnes, but did not achieve the MIC90 values against Enterococcus faecalis and Pseudomonas aeruginosa. The FMOX concentrations in the aqueous humor sampling were adequate to kill bacteria in vitro. This drug may be efficacious in the prevention of postoperative endophthalmitis in patients undergoing cataract surgery.

  17. Comparison between fish and linseed oils administered orally for ...

    African Journals Online (AJOL)

    The objective of this study was to compare the efficacy of two sources of omega 3 and 6, fish oil (FO) and linseed oil (LO), orally administered, alone or in combination, for treating experimentally induced keratoconjunctivitis sicca (KCS) in rabbits. Twenty-eight New Zealand rabbits were used in this study. Seven animals ...

  18. The role of intraperitoneally administered vitamin C during ...

    African Journals Online (AJOL)

    The effects of daily intraperitoneally administered doses of 100 mg/kg bd. wt. vitamin C on levels of some endogenous antioxidants as well as hepatic and renal function were investigated in a group of rabbits infected with a strain of Trypanosoma congolense (strain number: BS2/TC /SP28/P4). Values of parameters ...

  19. Effect of lead acetate administered orally at different dosage levels ...

    African Journals Online (AJOL)

    The project was conducted to evaluate the effect of lead administered as lead acetate at different dosage levels via drinking water in broiler chicks. Thirty-five healthy chicks were divided into seven groups (five chicks each) and one group was kept as un-medicated control. Groups A, B, C, D, E and F were medicated with ...

  20. Potency Studies of live- Attenuated Viral Vaccines Administered in ...

    African Journals Online (AJOL)

    We critically carried out a potency study in 1992 and 1997 on measles and poliovirus vaccines administered at five different vaccination centers in the metropolitan Lagos, Nigeria. using WHO guidelines on titration of live- viral vaccines, our results revealed that only 6 (16.7%) of 36 measles vaccine (MV) vials and 11 ...

  1. Moderate and deep nurse-administered propofol sedation is safe

    DEFF Research Database (Denmark)

    Jensen, Jeppe Thue; Møller, Ann; Hornslet, Pernille

    2015-01-01

    INTRODUCTION: Non-anaesthesiologist-administered propofol sedation (NAPS/NAAP) is increasingly used in many countries. Most regimens aim for light or moderate sedation. Little evidence on safety of deep NAPS sedation is available. The aim of this study was to explore the safety of intermittent deep...

  2. Statistical analysis of Japanese Thorotrast-administered autopsy cases

    International Nuclear Information System (INIS)

    Mori, T.; Kato, Y.; Shimamine, T.; Watanabe, S.

    1979-01-01

    The causes of death of 144 Japanese autopsy cases during 1945-1975, who had been intravascularly injected with Thorotrast in life, were compared with those of non-Thorotrast-administered autopsy cases in the same age bracket, recorded in the Annals of Japanese Pathological Autopsy Cases during 1958-1973. This comparison revealed that the incidence of malignant hepatic tumors was more than 10 times higher in the Thorotrast-administered cases. The increase was attributable to an increased incidence of hemangioendothelioma and cholangiocarcinoma of the liver. The only significant increase of liver cirrhosis found to exist in the Thorotrast group occurred in the female cases. Some of the Thorotrast-administered cases were found to have developed myeloid leukemia and erythroleukemia. There was also a significant increase in the number of cases of aplastic anemia in the Thorotrast group, but clinically and pathologically these were atypical. Lymphatic leukemia was not observed. No significant difference was found in the incidence of either malignant lymphomas or osteosarcomas in the Thorotrast group and the controls. Lung cancer, on the other hand, showed a significantly higher incidence among the controls than among the Thorotrast-administered cases

  3. 40 CFR 282.50 - Alabama State-Administered Program.

    Science.gov (United States)

    2010-07-01

    ... financial responsibility for hazardous substance underground storage tank systems. (2) Statement of legal... administered by the Alabama Department of Environmental Management, was approved by EPA pursuant to 42 U.S.C... obtained from the Ground Water Branch, Alabama Department of Environmental Management, 1751 W.L. Dickinson...

  4. 40 CFR 147.2500 - State-administered program.

    Science.gov (United States)

    2010-07-01

    ... State-administered program: (1) Chapter 144, Water, Sewage, Refuse, Mining and Air Pollution, Wisconsin... Section 147.2500 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS... Treatment Works, Wisconsin Administrative Code § 210.05 Natural Resources Board Order No. WQ-25-82, approved...

  5. 40 CFR 147.550 - State-administered program.

    Science.gov (United States)

    2010-07-01

    ... (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Georgia § 147.550...'s program application: (a) Incorporation by reference. The requirements set forth in the State... Hazardous Waste Management Act, O.C.G.A. §§ 12-8-60 through 12-8-83 (1988); (7) Georgia Safe Drinking Water...

  6. Repetitive immunization enhances the susceptibility of mice to peripherally administered prions.

    Directory of Open Access Journals (Sweden)

    Juliane Bremer

    Full Text Available The susceptibility of humans and animals to prion infections is determined by the virulence of the infectious agent, by genetic modifiers, and by hitherto unknown host and environmental risk factors. While little is known about the latter two, the activation state of the immune system was surmised to influence prion susceptibility. Here we administered prions to mice that were repeatedly immunized by two initial injections of CpG oligodeoxynucleotides followed by repeated injections of bovine serum albumin/alum. Immunization greatly reduced the required dosage of peripherally administered prion inoculum necessary to induce scrapie in 50% of mice. No difference in susceptibility was observed following intracerebral prion challenge. Due to its profound impact onto scrapie susceptibility, the host immune status may determine disease penetrance after low-dose prion exposure, including those that may give rise to iatrogenic and variant Creutzfeldt-Jakob disease.

  7. Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

    International Nuclear Information System (INIS)

    Li, Bin; Eyer, Peter; Eddleston, Michael; Jiang, Wei; Schopfer, Lawrence M.; Lockridge, Oksana

    2013-01-01

    Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5 days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos. - Highlights: • Chlorpyrifos-poisoned patients have adducts on protein tyrosine. • Diethoxyphosphate-tyrosine does not lose an alkyl group. • Proteins in addition to AChE and BChE are modified by organophosphates

  8. Protein tyrosine adduct in humans self-poisoned by chlorpyrifos

    Energy Technology Data Exchange (ETDEWEB)

    Li, Bin, E-mail: binli@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Eyer, Peter, E-mail: peter.eyer@lrz.uni-muenchen.de [Walther-Straub-Institut Für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, 80336 München (Germany); Eddleston, Michael, E-mail: M.Eddleston@ed.ac.uk [Clinical Pharmacology Unit, University of Edinburgh, Edinburgh (United Kingdom); Jiang, Wei, E-mail: wjiang@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Schopfer, Lawrence M., E-mail: lmschopf@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States); Lockridge, Oksana, E-mail: olockrid@unmc.edu [Eppley Institute, University of Nebraska Medical Center, Omaha, NE 68198-5950 (United States)

    2013-06-15

    Studies of human cases of self-inflicted poisoning suggest that chlorpyrifos oxon reacts not only with acetylcholinesterase and butyrylcholinesterase but also with other blood proteins. A favored candidate is albumin because in vitro and animal studies have identified tyrosine 411 of albumin as a site covalently modified by organophosphorus poisons. Our goal was to test this proposal in humans by determining whether plasma from humans poisoned by chlorpyrifos has adducts on tyrosine. Plasma samples from 5 self-poisoned humans were drawn at various time intervals after ingestion of chlorpyrifos for a total of 34 samples. All 34 samples were analyzed for plasma levels of chlorpyrifos and chlorpyrifos oxon (CPO) as a function of time post-ingestion. Eleven samples were analyzed for the presence of diethoxyphosphorylated tyrosine by mass spectrometry. Six samples yielded diethoxyphosphorylated tyrosine in pronase digests. Blood collected as late as 5 days after chlorpyrifos ingestion was positive for CPO-tyrosine, consistent with the 20-day half-life of albumin. High plasma CPO levels did not predict detectable levels of CPO-tyrosine. CPO-tyrosine was identified in pralidoxime treated patients as well as in patients not treated with pralidoxime, indicating that pralidoxime does not reverse CPO binding to tyrosine in humans. Plasma butyrylcholinesterase was a more sensitive biomarker of exposure than adducts on tyrosine. In conclusion, chlorpyrifos oxon makes a stable covalent adduct on the tyrosine residue of blood proteins in humans who ingested chlorpyrifos. - Highlights: • Chlorpyrifos-poisoned patients have adducts on protein tyrosine. • Diethoxyphosphate-tyrosine does not lose an alkyl group. • Proteins in addition to AChE and BChE are modified by organophosphates.

  9. Metabolism and excretion of orally and intraperitoneally administered methylarsonic acid in the hamster

    Energy Technology Data Exchange (ETDEWEB)

    Yamauchi, H.; Yamato, N.; Yamamura, Y.

    1988-02-01

    A number of investigators have demonstrated that when inorganic arsenic is administered to humans and experimental animals, methylarsonic acid (MAA) is formed in vivo. Low concentrations of MAA have been detected in human organs and urine. Few studies of the metabolism and elimination of MAA have been published. Following administration of a single oral dose of MAA to human subject, it was reported that MAA was rapidly metabolized to dimethylarsinic acid (DMAA) in vivo and excreted in urine. While the elimination of MAA has been investigated experimentally in animals, nothing is known of MAA metabolism and distribution in vivo. In the present study, the metabolism of MAA was investigated following its administration to hamsters. Arsenic species deposited in selected organs and blood, and the amounts and chemical species of arsenic excreted in urine and feces were determined.

  10. Efficacy and safety of intravenous fentanyl administered by ambulance personnel

    DEFF Research Database (Denmark)

    Friesgaard, Kristian Dahl; Nikolajsen, Lone; Giebner, Matthias

    2016-01-01

    BACKGROUND: Management of pain in the pre-hospital setting is often inadequate. In 2011, ambulance personnel were authorized to administer intravenous fentanyl in the Central Denmark Region. The aim of this study was to evaluate the efficacy and safety of intravenous fentanyl administered...... by ambulance personnel. METHODS: Pre-hospital medical charts from 2348 adults treated with intravenous fentanyl by ambulance personnel during a 6-month period were reviewed. The primary outcome was the change in pain intensity on a numeric rating scale (NRS) from before fentanyl treatment to hospital arrival...... patients (1.3%) and hypotension observed in 71 patients (3.0%). CONCLUSION: Intravenous fentanyl caused clinically meaningful pain reduction in most patients and was safe in the hands of ambulance personnel. Many patients had moderate to severe pain at hospital arrival. As the protocol allowed higher doses...

  11. Relative bioavailability, metabolism and tolerability of rectally administered oxcarbazepine suspension.

    Science.gov (United States)

    Clemens, Pamela L; Cloyd, James C; Kriel, Robert L; Remmel, Rory P

    2007-01-01

    Maintenance of effective drug concentrations is essential for adequate treatment of epilepsy. Some antiepileptic drugs can be successfully administered rectally when the oral route of administration is temporarily unavailable. Oxcarbazepine is a newer antiepileptic drug that is rapidly converted to a monohydroxy derivative, the active compound. This study aimed to characterise the bioavailability, metabolism and tolerability of rectally administered oxcarbazepine suspension using a randomised, crossover design in ten healthy volunteers. Two subjects received 300 mg doses of oxcarbazepine suspension via rectal and oral routes and eight received 450 mg doses. A washout period of at least 2 weeks elapsed between doses. The rectal dose was diluted 1:1 with water. Blood samples and urine were collected for 72 hours post-dose. Adverse effects were assessed at each blood collection time-point using a self-administered questionnaire. Plasma was assayed for oxcarbazepine and monohydroxy derivative; urine was assayed for monohydroxy derivative and monohydroxy derivative-glucuronide. Maximum plasma concentration (C(max)) and time to reach C(max) (t(max)) were obtained directly from the plasma concentration-time curves. The areas under the concentration-time curve (AUCs) were determined via non-compartmental analysis. Relative bioavailability was calculated and the C(max) and AUCs were compared using Wilcoxon signed-rank tests. Mean relative bioavailability calculated from plasma AUCs was 8.3% (SD 5.5%) for the monohydroxy derivative and 10.8% (SD 7.3%) for oxcarbazepine. Oxcarbazepine and monohydroxy derivative C(max) and AUC values were significantly lower following rectal administration (p effects were headache and fatigue with no discernible differences between routes. Monohydroxy derivative bioavailability following rectal administration of oxcarbazepine suspension is significantly lower than following oral administration, most likely because of poor oxcarbazepine water

  12. Problem of administering radioactive substances to pregnant women

    International Nuclear Information System (INIS)

    Husak, V.; Ryznar, V.; Klener, V.

    1987-01-01

    Based on a critical analysis of a large amount of data from the literature, a table was prepared of radiation loads of the fetus after administration of radiopharmaceuticals to pregnant women. Briefly mentioned are recent findings on the biological effects of ionizing radiation on the fetus and the radiation risk was evaluated of radiopharmaceuticals administered during the third trimester of pregnancy. The possibility is discussed to evaluate the benefit of radionuclide examinations of pregnant women in relation to the radiation risk. (author). 4 figs., 4 tabs., 31 refs

  13. Administering an epoch initiated for remote memory access

    Science.gov (United States)

    Blocksome, Michael A; Miller, Douglas R

    2012-10-23

    Methods, systems, and products are disclosed for administering an epoch initiated for remote memory access that include: initiating, by an origin application messaging module on an origin compute node, one or more data transfers to a target compute node for the epoch; initiating, by the origin application messaging module after initiating the data transfers, a closing stage for the epoch, including rejecting any new data transfers after initiating the closing stage for the epoch; determining, by the origin application messaging module, whether the data transfers have completed; and closing, by the origin application messaging module, the epoch if the data transfers have completed.

  14. Chromosome abnormalities in bone marrow of Thorotrast administered patients

    International Nuclear Information System (INIS)

    Ishihara, T.; Minamihisamatsu, M.

    1987-01-01

    The chromosomally abnormal clones occurring with high frequencies in bone marrow of 3 Thorotrast administered patients were studied by annual follow up observations. In one case the frequency of the clone was maintained fairly constant, but in another case it showed a tendency of increase, and in still another case the frequency of the clone showed drastic changes from year to year. The karyotypes of the clones showed remarkable chromosome abnormalities, among which the large partial loss of chromosomes was especially noted in all the 3 cases. (author)

  15. Absorption and distribution of orally administered jojoba wax in mice.

    Science.gov (United States)

    Yaron, A; Samoiloff, V; Benzioni, A

    1982-03-01

    The liquid wax obtained from the seeds of the arid-land shrub jojoba (Simmondsia chinensis) is finding increasing use in skin treatment preparations. The fate of this wax upon reaching the digestive tract was studied. 14C-Labeled wax was administered intragastrically to mice, and the distribution of the label in the body was determined as a function of time. Most of the wax was excreted, but a small amount was absorbed, as was indicated by the distribution of label in the internal organs and the epididymal fat. The label was incorporated into the body lipids and was found to diminish with time.

  16. Preclinical safety evaluation of intravenously administered mixed micelles.

    Science.gov (United States)

    Teelmann, K; Schläppi, B; Schüpbach, M; Kistler, A

    1984-01-01

    Mixed micelles, with their main constituents lecithin and glycocholic acid, form a new principle for the parenteral administration of compounds which are poorly water-soluble. Their composition of mainly physiological substances as well as their comparatively good stability substantiate their attractivity in comparison to existing solvents. A decomposition due to physical influences such as heat or storage for several years will almost exclusively affect the lecithin component in the form of hydrolysis into free fatty acids and lysolecithin. Their toxicity was examined experimentally in various studies using both undecomposed and artificially decomposed mixed micelles. In these studies the mixed micelles were locally and systemically well tolerated and proved to be neither embryotoxic, teratogenic nor mutagenic. Only when comparatively high doses of the undecomposed mixed micelles were administered, corresponding to approximately 30 to 50 times the anticipated clinical injection volume (of e.g. diazepam mixed micelles), did some vomitus (dogs), slight liver enzyme elevation (rats and dogs), and slightly increased liver weights (dogs) occur. After repeated injections of the artificially decomposed formulation (approximately 25% of lecithin hydrolyzed to free fatty acids and lysolecithin) effects such as intravascular haemolysis, liver enzyme elevations and intrahepatic cholestasis (dogs only) were observed but only when doses exceeding a threshold of approximately 40 to 60 mg lysolecithin/kg body weight were administered. All alterations were reversible after cessation of treatment.

  17. Metabolism of exogenously administered natural surfactant in the newborn lamb

    Energy Technology Data Exchange (ETDEWEB)

    Glatz, T.; Ikegami, M.; Jobe, A.

    1982-09-01

    (/sup 3/H)-Palmitate labeled natural lamb surfactant and free (/sup 14/C)-choline were mixed with the lung fluid of 11 term lambs at cesarean section, before the first breath. After receiving the isotope, the lambs were delivered, allowed to breathe spontaneously, and were subsequently sacrificed from 5 min to 96 h of age. Alveolar washes, lung homogenates, microsomal and lamellar body fractions of lungs, and pulmonary alveolar macrophages were examined for the presence of labeled phosphatidylcholine. Analysis of the labeled natural surfactant kinetic data revealed an apparent t 1/2 of phosphatidylcholine in the whole lung of 6.0 days. This half-life can be interpreted only as a rough estimate. Appearance of considerable (/sup 3/H) labeled phosphatidylcholine in the lung homogenates demonstrated uptake of phosphatidylcholine from alveoli into lung tissue. The surfactant-associated label in homogenates was localized preferentially to lamellar body fractions. Some of the administered (/sup 14/C)-choline appeared in phosphatidylcholine. Almost all of this labeled phosphatidylcholine was associated with the homogenate. Extremely small % of administered (3H) and (14C) were found in pulmonary alveolar macrophages.

  18. 34 CFR 461.1 - What is the Adult Education State-administered Basic Grant Program?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What is the Adult Education State-administered Basic...-ADMINISTERED BASIC GRANT PROGRAM General § 461.1 What is the Adult Education State-administered Basic Grant Program? The Adult Education State-administered basic Grant Program (the program) is a cooperative effort...

  19. Bioavailability of pivampicillin and ampicillin trihydrate administered as an oral paste in horses

    NARCIS (Netherlands)

    Ensink, JM; Mol, A; Vulto, AG; Tukker, JJ

    1996-01-01

    Pivampicillin was administered as an oral paste to five healthy adult horses, and an oral paste with ampicillin trihydrate was administered to three horses, Pivampicillin was administered to both starved and fed horses, ampicillin trihydrate was administered to fed horses only, The dose of

  20. A Controlled Study to Assess the Clinical Efficacy of Totally Self-Administered Systematic Desensitization

    Science.gov (United States)

    Rosen, Gerald M.; And Others

    1976-01-01

    Highly anxious self-referred snake phobics received either (a) therapist-administered desensitization, (b) self-administered desensitization with weekly therapist phone calls, (c) totally self-administered desensitization, (d) self-administered double-blind placebo control, or (e) no treatment. Pretreatment to posttreatment measures revealed…

  1. A randomized trial comparing surgeon-administered intraoperative transversus abdominis plane block with anesthesiologist-administered transcutaneous block.

    Science.gov (United States)

    Narasimhulu, D M; Scharfman, L; Minkoff, H; George, B; Homel, P; Tyagaraj, K

    2018-04-27

    Injection of local anesthetic into the transversus abdominis plane (TAP block) decreases systemic morphine requirements after abdominal surgery. We compared intraoperative surgeon-administered TAP block (surgical TAP) to anesthesiologist-administered transcutaneous ultrasound-guided TAP block (conventional TAP) for post-cesarean analgesia. We hypothesized that surgical TAP blocks would take less time to perform than conventional TAP blocks. We performed a randomized trial, recruiting 41 women undergoing cesarean delivery under neuraxial anesthesia, assigning them to either surgical TAP block (n=20) or conventional TAP block (n=21). Time taken to perform the block was the primary outcome, while postoperative pain scores and 24-hour opioid requirements were secondary outcomes. Student's t-test was used to compare block time and Kruskal-Wallis test opioid consumption and pain-scores. Time taken to perform the block (2.4 vs 12.1 min, P consumption (P=0.17) and postoperative pain scores at 4, 8, 24 and 48 h were not significantly different between the groups. Surgical TAP blocks are feasible and less time consuming than conventional TAP blocks, while providing comparable analgesia after cesarean delivery. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Haematological disorders in Thorotrast-administered patients in Japan

    International Nuclear Information System (INIS)

    Kamiyama, Ryuichi; Hatakeyama, Shigeru

    1989-01-01

    Fifteen haematological disorders including ten leukaemia cases, one primary acquired sideroblastic anaemia and four aplastic anaemia cases were studied clinicopathologically in autopsies from patients who had been administered Thorotrast in Japan. The leukaemia group, the primary acquired sideroblastic anaemia and the aplastic anaemia cases after Thorotrast administration were considered to be mainly atypical, and it was speculated that damage induced by Thorotrast may affect the haemopoietic stem cell level and the haemopoietic microenvironment. Both dose rate and absorbed dose estimated in bone marrow, spleen and liver at autopsy showed no significant difference between the leukaemia group, primary acquired sideroblastic anaemia, aplastic anaemia and non-haematological disorders excluding the malignant hepatic tumours and liver cirrhosis. (author)

  3. Administering truncated receive functions in a parallel messaging interface

    Science.gov (United States)

    Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

    2014-12-09

    Administering truncated receive functions in a parallel messaging interface (`PMI`) of a parallel computer comprising a plurality of compute nodes coupled for data communications through the PMI and through a data communications network, including: sending, through the PMI on a source compute node, a quantity of data from the source compute node to a destination compute node; specifying, by an application on the destination compute node, a portion of the quantity of data to be received by the application on the destination compute node and a portion of the quantity of data to be discarded; receiving, by the PMI on the destination compute node, all of the quantity of data; providing, by the PMI on the destination compute node to the application on the destination compute node, only the portion of the quantity of data to be received by the application; and discarding, by the PMI on the destination compute node, the portion of the quantity of data to be discarded.

  4. Techniques to administer oral, inhalational, and IV sedation in dentistry

    Directory of Open Access Journals (Sweden)

    Diana Krystyna Harbuz

    2016-02-01

    Full Text Available Background Sedation in dentistry is a controversial topic given the variety of opinions regarding its safe practice. Aims This article evaluates the various techniques used to administer sedation in dentistry and specific methods practiced to form a recommendation for clinicians. Methods An extensive literature search was performed using PubMed, Medline, Google Scholar, Google, and local library resources. Results Most of the literature revealed a consensus that light sedation on low-risk American Society of Anesthesiologists (ASA groups, that is ASA I, and possibly II, is the safest method for sedation in a dental outpatient setting. Conclusion Formal training is essential to achieve the safe practice of sedation in dentistry or medicine. The appropriate setting for sedation should be determined as there is an increased risk outside the hospital setting. Patients should be adequately assessed and medication titrated appropriately, based on individual requirements.

  5. Radiopharmaceutical activities administered for paediatric nuclear medicine procedures in Australia

    International Nuclear Information System (INIS)

    Towson, J.E.; Smart, R.C.; Rossleigh, M.A.; Children's Hospital, Randwick, NSW

    2000-01-01

    A survey of radiopharmaceutical activities used at the eight hospital centres specialising in paediatric nuclear medicine in Australia was conducted in 1999-2000 by the Australian and New Zealand Society of Nuclear Medicine and the Australasian Radiation Protection Society. Data on the maximum and minimum administered activities was obtained for 43 paediatric imaging procedures. The maximum values were significantly less than the corresponding Reference Activities for adults determined in a previous study. Activities for individual patients are calculated using surface area scaling at five centres and body weight scaling at three centres. The median values of A max and A min are recommended as Paediatric Reference Activities. The effective dose to patients of various sizes for the Paediatric Reference Activities and both methods of scaling was calculated for each procedure. Copyright (2000) Australasian Radiation Protection Society Inc

  6. Safety of florfenicol administered in feed to tilapia (Oreochromis sp.)

    Science.gov (United States)

    Gaikowski, Mark P.; Wolf, Jeffrey C.; Schleis, Susan M.; Tuomari, Darrell; Endris, Richard G.

    2013-01-01

    The safety of Aquaflor® (50% w/w florfenicol [FFC]) incorporated in feed then administered to tilapia for 20 days (2x the recommended duration) at 0, 15, 45, or 75 mg/kg body weight/day (0, 1, 3, or 5x the recommended dose of 15 mg FFC/kg BW/d) was investigated. Mortality, behavioral change, feed consumption, body size, and gross and microscopic lesions were determined. Estimated delivered doses were >96.9% of target. Three unscheduled mortalities occurred but were considered incidental since FFC-related findings were not identified. Feed consumption was only affected during the last 10 dosing days when the 45 and 75 mg/kg groups consumed only 62.5% and 55.3% of the feed offered, respectively. There were significant, dose-dependent reductions in body size in the FFC-dose groups relative to the controls. Treatment-related histopathological findings included increased severity of lamellar epithelial hyperplasia, increased incidence of lamellar adhesions, decreased incidence of lamellar telangiectasis in the gills, increased glycogen-type and lipid-type hepatocellular vacuolation in the liver, decreased lymphocytes, increased blast cells, and increased individual cell necrosis in the anterior kidney, and tubular epithelial degeneration and mineralization in the posterior kidney. These changes are likely to be of minimal clinical relevance, given the lack of mortality or morbidity observed. This study has shown that FFC, when administered in feed to tilapia at the recommended dose (15 mg FFC/kg BW/day) for 10 days would be well tolerated.

  7. Opponent process properties of self-administered cocaine.

    Science.gov (United States)

    Ettenberg, Aaron

    2004-01-01

    Over the past decade, data collected in our laboratory have demonstrated that self-administered cocaine produces Opponent-Process-like behavioral effects. Animals running a straight alley once each day for IV cocaine develop over trials an approach-avoidance conflict about re-entering the goal box. This conflict behavior is characterized by a stop in forward locomotion (usually at the very mouth of the goal box) followed by a turn and 'retreat' back toward the goal box. The results of a series of studies conducted over the past decade collectively suggest that the behavioral ambivalence exemplified by rats running the alley for IV cocaine stems from concurrent and opponent positive (rewarding) and negative (anxiogenic) properties of the drug--both of which are associated with the goal box. These opponent properties of cocaine have been shown to result from temporally distinct affective states. Using a conditioned place preference test, we have been able to demonstrate that while the initial immediate effects of IV cocaine are reinforcing, the state present 15 min post-injection is aversive. In our most recent work, the co-administration of IV cocaine with either oral ethanol or IV heroin was found to greatly diminish the development and occurrence of retreat behaviors in the runway. It may therefore be that the high incidence of co-abuse of cocaine with either ethanol or heroin, stems from the users' motivation to alleviate some of the negative side effects of cocaine. It would seem then that the Opponent Process Theory has provided a useful conceptual framework for the study of the behavioral consequences of self-administered cocaine including the notion that both positive and negative reinforcement mechanisms are involved in the development and maintenance of cocaine abuse.

  8. Police Officers Can Safely and Effectively Administer Intranasal Naloxone.

    Science.gov (United States)

    Fisher, Rian; O'Donnell, Daniel; Ray, Bradley; Rusyniak, Daniel

    2016-01-01

    Opioid overdose rates continue to rise at an alarming rate. One method used to combat this epidemic is the administration of naloxone by law enforcement. Many cities have implemented police naloxone administration programs, but there is a minimal amount of research examining this policy. The following study examines data over 18 months, after implementation of a police naloxone program in an urban setting. We describe the most common indications and outcomes of naloxone administration as well as examine the incidence of arrest, immediate detention, or voluntary transport to the hospital. In doing so, this study seeks to describe the clinical factors surrounding police use of naloxone, and the effects of police administration. All police officer administrations were queried from April 2014 through September 2015 (n = 126). For each incident we collected the indication, response, and disposition of the patient that was recorded on a "sick-injured civilian" report that officers were required to complete after administration of naloxone. All of the relevant information was abstracted from this report into an electronic data collection form that was then input into SPSS for analysis. The most common indication for administration was unconscious/unresponsive (n = 117; 92.9%) followed by slowed breathing (n = 72; 57.1%), appeared blue (n = 63; 50.0%) and not breathing (n = 41; 32.5%). After administration of naloxone the majority of patients regained consciousness (n = 82; 65.1%) followed by began to breath (n = 71; 56.3%). However, in 17.5% (n = 22) of the cases "Nothing" happened when naloxone was administered. The majority of patients were transported voluntarily to the hospital (n = 122; 96.8%). Lastly, there was only one report where the patient became combative. Our study shows that police officers trained in naloxone administration can correctly recognize symptoms of opioid overdose, and can appropriately administer naloxone without significant adverse effects or

  9. Toxicity of Hypericum perforatum (St. John's wort) administered during pregnancy and lactation in rats

    International Nuclear Information System (INIS)

    Gregoretti, Barbara; Stebel, Marco; Candussio, Luigi; Crivellato, Enrico; Bartoli, Fiora; Decorti, Giuliana

    2004-01-01

    The popularity of St. John's wort (Hypericum perforatum) for the treatment of depression is increasing and, in recent years, concerns about its use during pregnancy and breastfeeding have emerged. The purpose of this study was to investigate, in Wistar rats, the effects of a treatment with hypericum administered prenatally and during breastfeeding (from 2 weeks before mating to 21 days after delivery). Two doses of the extract were chosen, 100 mg/kg per day, which, based on surface area, is comparable to the dose administered to humans, and 1000 mg/kg per day. A microscopical analysis of livers, kidneys, hearts, lungs, brains, and small bowels was performed. A severe damage was observed in the livers and kidneys of animals euthanized postnatally on days 0 and 21. The lesions were more severe with the higher dose and in animals that were breastfed for 21 days; however, an important renal and hepatic damage was evident also with the dose of 100 mg/kg per day. In addition, similar serious hepatic and renal lesions were evident also in animals that were exposed to hypericum only during breastfeeding. In particular, a focal hepatic damage, with vacuolization, lobular fibrosis, and disorganization of hepatic arrays was evident; in the kidney, a reduction in glomerular size, disappearance of Bowman's space, and hyaline tubular degeneration were found. The results obtained in this study indicate that further, appropriate histological studies should be performed in other animal species to better evaluate the safety of hypericum extracts taken during pregnancy and breastfeeding

  10. Therapeutic effect of rhIL-11 administered at different times on acute radiation sickness in rhesus monkeys

    International Nuclear Information System (INIS)

    Hao Jing; Luo Qingliang; Xiong Guolin; Liu Xiaolan; Qiu Liling; Chen Guozhi; Huang Ying; Ge Ping; Geng Yu; Sun Liansheng; Dong Bo; Li Yuanmin; Chen Wangqiu; Shen Chun

    2001-01-01

    Objective: The author describes the therapeutic effect of recombinant human interleukin-11 (rhIL-11) administered at different times on acute radiation sickness in monkeys. Methods: Rhesus monkeys irradiated with 3.0 Gy 60 Co γ rays were divided into 3 groups. One group was the control administered with vehicle, the second one was subjected to administer rhIL-11 on days 0-13 after TBI (60 μg·kg -1 ·d -1 , sc) and the third one to administer rhIL-11 on days 13-26 after TBI at the same doses. Results: The early treated group had higher platelet nadirs compared with that of the other two. The duration of platelet and leukocyte numbers below 50% of their baseline values shortened significantly in animals treated with rhIL-11, especially in the early treated group. During the first week after irradiation, the early treated group had lower erythrocyte count compared with the control, but it began to rise at day 19 after irradiation. Semi-solid bone marrow cell culture demonstrated that rhIL-11 could stimulate bone marrow cells to form more CFU-MK, CFU-Mix, CFU-E, BFU-E and CFU-GM in vitro. The authors also got the same results in histopathological observation. Conclusion: rhIL-11 administered at different times can not only accelerate the haematopoietic recovery of acute radiation sickness in rhesus monkeys, but also result in better therapeutic effect when administered earlier

  11. Toxicity and biodistribution of orally administered casein nanoparticles.

    Science.gov (United States)

    Gil, Ana Gloria; Irache, Juan Manuel; Peñuelas, Iván; González Navarro, Carlos Javier; López de Cerain, Adela

    2017-08-01

    In the last years, casein nanoparticles have been proposed as carriers for the oral delivery of biologically active compounds. However, till now, no information about their possible specific hazards in vivo was available. The aim of this work was to assess the safety of casein nanoparticles when administered orally to animals through a 90 days dose-repeated toxicity study (OECD guideline 408), that was performed in Wistar rats under GLP conditions. After 90 days, no evidences of significant alterations in animals treated daily with 50, 150 or 500 mg/kg bw of nanoparticles were found. This safety agrees well with the fact that nanoparticles were not absorbed and remained within the gut as observed by radiolabelling in the biodistribution study. After 28 days, there was a generalized hyperchloremia in males and females treated with the highest dose of 500 mg/kg bw, that was coupled with hypernatremia in the females. These effects were related to the presence of mannitol which was used as excipient in the formulation of casein nanoparticles. According to these results, the No Observed Adverse Effect Level (NOAEL) could be established in 150 mg/kg bw/day and the Lowest Observed Effect Level (LOEL) could be established in 500 mg/kg bw/day. Copyright © 2017. Published by Elsevier Ltd.

  12. Macroscopic and microscopic biodistribution of intravenously administered iron oxide nanoparticles

    Science.gov (United States)

    Misra, Adwiteeya; Petryk, Alicia A.; Strawbridge, Rendall R.; Hoopes, P. Jack

    2015-03-01

    Iron oxide nanoparticles (IONP) are being developed for use as a cancer treatment. They have demonstrated efficacy when used either as a monotherapy or in conjunction with conventional chemotherapy and radiation. The success of IONP as a therapeutic tool depends on the delivery of a safe and controlled cytotoxic thermal dose to tumor tissue following activation with an alternating magnetic field (AMF). Prior to clinical approval, knowledge of IONP toxicity, biodistribution and physiological clearance is essential. This preliminary time-course study determines the acute toxicity and biodistribution of 110 nm dextran-coated IONP (iron) in mice, 7 days post systemic, at doses of 0.4, 0.6, and 1.0 mg Fe/ g mouse bodyweight. Acute toxicity, manifested as changes in the behavior of mice, was only observed temporarily at 1.0 mg Fe/ g mouse bodyweight, the highest dose administered. Regardless of dose, mass spectrometry and histological analysis demonstrated over 3 mg Fe/g tissue in organs within the reticuloendotheilial system (i.e. liver, spleen, and lymph nodes). Other organs (brain, heart, lungs, and kidney) had less than 0.5 mg Fe/g tissue with iron predominantly confined to the organ vasculature.

  13. Developmental toxicity of orally administered pineapple leaf extract in rats.

    Science.gov (United States)

    Hu, Jun; Lin, Han; Shen, Jia; Lan, Jiaqi; Ma, Chao; Zhao, Yunan; Lei, Fan; Xing, Dongming; Du, Lijun

    2011-06-01

    The extract of pineapple leaves (EPL) has anti-diabetic and anti-dyslipidemic effects and can be developed into a promising natural medicine. This study was conducted to evaluate EPL's effects on developmental parameters in order to provide evidence of its safety before potential medical use. Five groups were included: a negative control that was given distilled water daily, a positive control that was dosed 7 mg/kg cyclophosphamide (CP) every two days, and three groups that were respectively dosed 2.0, 1.0, and 0.5 g/kg EPL daily. Female rats were dosed during the organogenesis period of gestation days (GD) 7-17 and terminated on GD 20. A series of parameters were examined. Data revealed that CP significantly reduced maternal body weight gains, caused maternal organ weight alterations, reduced female fertility, disturbed fetal growth and development, and caused marked teratogenic effects on fetal appearances, skeleton and internal organs. Distilled water and the three high doses of EPL did not cause any of the aforementioned effects. This study concluded that orally administered EPL is safe to rats during embryonic development. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Administering and Detecting Protein Marks on Arthropods for Dispersal Research.

    Science.gov (United States)

    Hagler, James R; Machtley, Scott A

    2016-01-28

    Monitoring arthropod movement is often required to better understand associated population dynamics, dispersal patterns, host plant preferences, and other ecological interactions. Arthropods are usually tracked in nature by tagging them with a unique mark and then re-collecting them over time and space to determine their dispersal capabilities. In addition to actual physical tags, such as colored dust or paint, various types of proteins have proven very effective for marking arthropods for ecological research. Proteins can be administered internally and/or externally. The proteins can then be detected on recaptured arthropods with a protein-specific enzyme-linked immunosorbent assay (ELISA). Here we describe protocols for externally and internally tagging arthropods with protein. Two simple experimental examples are demonstrated: (1) an internal protein mark introduced to an insect by providing a protein-enriched diet and (2) an external protein mark topically applied to an insect using a medical nebulizer. We then relate a step-by-step guide of the sandwich and indirect ELISA methods used to detect protein marks on the insects. In this demonstration, various aspects of the acquisition and detection of protein markers on arthropods for mark-release-recapture, mark-capture, and self-mark-capture types of research are discussed, along with the various ways that the immunomarking procedure has been adapted to suit a wide variety of research objectives.

  15. Association between systemically administered radioisotopes and subsequent malignant disease

    International Nuclear Information System (INIS)

    Berlin, N.I.; Wasserman, L.R.

    1976-01-01

    There is a long history recording the association of x radiation and the subsequent development of malignant tumors. For systemically administered isotopes this came into prominence when Martland discovered the association between cancer, particularly of the bone, and ingestion of radioactive isotopes by radium dial painters. This association was amplified by the development of cancer in patients given thorotrast as a contrast medium for diagnostic radiologic examination. Acute leukemia was reported 30 years ago in patients with polycythemia vera treated with 32 P. Acute leukemia also occurs in patients with polycythemia vera treated only with phlebotomy or drugs. A controlled study is now underway to provide a more definite answer to question what is the incidence of acute leukemia in patients with polycythemia vera treated by phlebotomy alone, chlorambucil, or 32 P. 131 I for the treatment of hyperthyroidism probably does not induce cancer, but in the doses used for thyroid cancer there was an increased incidence of neoplasms (12/200 in one study). This was higher than the expected incidence of neoplasms. The doses of radioactive isotopes used currently for diagnostic purposes have not induced cancer, but it is difficult and probably impossible to verify this with absolute certainty

  16. Radiopharmaceutical activities administered for paediatric nuclear medicine procedures in Australia

    International Nuclear Information System (INIS)

    Towson, J.E.; Smart, R.C.; Rossleigh, M.A.

    2001-01-01

    A survey of radiopharmaceutical activities used at the eight hospital centres specialising in paediatric nuclear medicine in Australia was conducted in 1999-2000 by the Australian and New Zealand Society of Nuclear Medicine and the Australasian Radiation Protection Society. Data on the maximum and minimum administered activities (A max and A min ) as obtained for 43 paediatric imaging procedures are presented. The results are also available on the ANZSNM and ARPS websites at: http://www.anzsnm.org.au and http://www.arps.org.au. The A max values were significantly less than the corresponding Reference Activities for adults determined in a previous study. Activities for individual patients are calculated using surface area scaling at five centres and body weight scaling at three centres. The median values of A max and A min are recommended as Paediatric Reference Activities. The effective dose to patients of various sizes for the Paediatric Reference Activities and both methods of scaling was calculated for each procedure. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  17. Comparison of the effects of peripherally administered kisspeptins

    DEFF Research Database (Denmark)

    Mikkelsen, Jens D; Bentsen, Agnete H; Ansel, Laura

    2008-01-01

    examined the acute effect on serum levels of free testosterone in the adult male mouse after systemic administration of kisspeptins with different lengths of both human and mouse origin. Mouse kisspeptin-10 and -52 dose-dependently increased serum testosterone, and both peptides showed similar potency...... and efficacy. Human kisspeptin-10 and kisspeptin-54 evoked robust increase in serum testosterone, with the same potency as for mouse kisspeptins. Other members of the RFRP family of peptides, i.e. RFRP-1 and -3 were inactive. Time-course experiments revealed that the longer forms had a slower onset of action...

  18. Dietary fibre supplementation of a 'normal' breakfast administered to diabetics.

    Science.gov (United States)

    Williams, D R; James, W P; Evans, I E

    1980-05-01

    The supplementation of a breakfast by 10 g of guar, pectin, agar or locust bean gum in powder form in 13 maturity onset, non-insulin dependent diabetics failed to decrease significantly the post-prandial rise in plasma glucose and insulin seen after a similar meal without the supplement. The values of one hour post-prandial increment in blood glucose seen with guar powder were, for control meal (mean +/- SEM) 5.8 %/- 0.4 mmol/l, for test, 5.7 +/- 0.5; with pectin powder, control 6.4 +/- 0.8 mmol/l, test 5.0 +/- 1.2 mmol/l; with agar powder, control 7.5 +/- 1.0, test 7.0 +/- 0.5; with locust bean gum powder, control 5.9 +/- 1.0, test 5.0 +/- 0.7. The equivalent values for one hour insulin (microU/ml, mean +/- SEM) were, for guar powder, 51 +/0 21 and 51 +/- 16; for pectin powder 60 +/- 24 and 63 +/- 17; for agar powder, 27 +/- 9 and 36 +/- 11 and, for locust bean gum powder 53 +/- 26 and 62 +/- 18. The guar, pectin and locust gum tended to form lumps, and all the substances tested were unpalatable in powder form producing feelings of abdominal discomfort and abnormal fullness. Administering the same quantity of guar or pectin in a well hydrated form (but not premixed with the carbohydrate portion of the food) to the same people under identical conditions did not enhance its effectiveness. Supplementing diets with any of these sources of dietary fibre in either of these forms and in these amounts is unlikely to be beneficial in the management of non-insulin dependent diabetes.

  19. Usefulness of recombinant human TSH aided radioiodine doses administered in patients with differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Pitoia, Fabian; El Tamer, Elias; Schere, Daniel B.; Passerieu, Mariano; Bruno, Oscar D.; Niepominiszcze, Hugo

    2006-01-01

    The published studies confirming the safety and efficacy of rh TSH for diagnostic purposes have led to an increased interest in its use for preparation for radioiodine (RI) dose administration in patients with recurrent or persistent differentiated thyroid carcinoma (DTC). In order to establish the efficacy of RI therapy after rh TSH, we have reviewed 39 rh TSH-aided radioiodine treatments in a series of 28 DTC patients. Patients were divided into two groups: GI (n=17), with previous thyroid bed uptake and undetectable thyroglobulin (Tg) levels under levothyroxine treatment and GII (n=11), with proven metastatic local or distant disease. Median follow-up after the first rh TSH-aided radioiodine treatment was 32 ± 13 months (range 8 to 54 months). Sixteen patients (94%) in GI were rendered disease free and one patient was shown to have persistent disease. In GII, the post therapy whole body scan showed pathological uptakes in all cases: in four patients in lungs, in four in mediastinum and in three in lateral neck. In two patients with mediastinum uptake, Tg levels were undetectable after rh TSH. In the follow-up, two patients with lateral neck uptake were rendered disease free, four patients died (three due to thyroid cancer) and five out of the remaining patients have persistent disease. In conclusion, rh TSH aided therapy was helpful to eliminate normal thyroid bed remnants in 16/17 (94%) patients (GI). rh TSH stimulated Tg was undetectable in two patients with mediastinal metastasis. We believe that rh TSH is a good alternative to levothyroxine withdrawal for the treatment of DTC with radioactive iodine, increasing the quality of life in these patients. Caution should be recommended in the follow-up of unselected DTC patients only with stimulated Tg levels. (author) [es

  20. Acute Toxicity of Intravenously Administered Titanium Dioxide Nanoparticles in Mice

    OpenAIRE

    Xu, Jiaying; Shi, Hongbo; Ruth, Magaye; Yu, Hongsheng; Lazar, Lissy; Zou, Baobo; Yang, Cui; Wu, Aiguo; Zhao, Jinshun

    2013-01-01

    BACKGROUND: With a wide range of applications, titanium dioxide (TiO₂) nanoparticles (NPs) are manufactured worldwide in large quantities. Recently, in the field of nanomedicine, intravenous injection of TiO₂ nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans. METHODS: In this study, mice were injected intravenously with a single dose of TiO₂ NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg). Animal mortality, blood biochem...

  1. 20 CFR 408.1215 - How do you establish eligibility for Federally administered State recognition payments?

    Science.gov (United States)

    2010-04-01

    ... Federally administered State recognition payments? 408.1215 Section 408.1215 Employees' Benefits SOCIAL... Recognition Payments § 408.1215 How do you establish eligibility for Federally administered State recognition... deemed to have filed an application for any Federally administered State recognition payments for which...

  2. 45 CFR 400.66 - Eligibility and payment levels in a publicly-administered RCA program.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 2 2010-10-01 2010-10-01 false Eligibility and payment levels in a publicly... REFUGEE RESETTLEMENT PROGRAM Refugee Cash Assistance § 400.66 Eligibility and payment levels in a publicly-administered RCA program. (a) In administering a publicly-administered refugee cash assistance program, the...

  3. 25 CFR 26.4 - Who administers the Job Placement and Training Program?

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Who administers the Job Placement and Training Program... PLACEMENT AND TRAINING PROGRAM General Applicability § 26.4 Who administers the Job Placement and Training Program? The Job Placement and Training Program is administered by the Bureau of Indian Affairs or a...

  4. Recombinant granulocyte colony-stimulating factor administered enterally to neonates is not absorbed.

    Science.gov (United States)

    Calhoun, Darlene A; Maheshwari, Akhil; Christensen, Robert D

    2003-08-01

    Granulocyte colony-stimulating factor (G-CSF) is present in liquids swallowed by the fetus and neonate; specifically, amniotic fluid, colostrum, and human milk. The swallowed G-CSF has local effects on enteric cells, which express the G-CSF receptor. However, some portion of the G-CSF ingested by the fetus and neonate might be absorbed into the circulation and have systemic actions, such as stimulating neutrophil production. To assess this possibility we sought to determine if circulating G-CSF concentrations of neonates increase after enteral administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF). This was a single-center, prospective, blinded, randomized, 2 x 2 crossover study, with each infant receiving 1 dose of rhG-CSF (100 microg/kg) and 1 dose of placebo. Plasma G-CSF concentrations were measured at 2 and 4 hours after administration of the test solution. No significant change in plasma G-CSF concentration was observed after the enteral administration of rhG-CSF. On this basis, we conclude that orally administered rhG-CSF is not absorbed in significant quantities, and we speculate that the G-CSF swallowed by the fetus and neonate has local but not systemic effects.

  5. Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine and Commonly Administered Vaccines After Coadministration.

    Science.gov (United States)

    Gasparini, Roberto; Tregnaghi, Miguel; Keshavan, Pavitra; Ypma, Ellen; Han, Linda; Smolenov, Igor

    2016-01-01

    Given the broad age range across which the quadrivalent meningococcal conjugate vaccine MenACWY-CRM is used, coadministration with routine vaccines should be evaluated across age groups for possible immunologic interference and impact on vaccine reactogenicity and safety. We summarize data from a large population of infants, adolescents and international travelers from 10 phase 3 or 4 clinical studies to evaluate coadministration of MenACWY-CRM with commonly administered vaccines. Noninferiority analyses of immune responses were performed across studies and age groups for each vaccine. Reactogenicity and safety were also assessed. In infants, MenACWY-CRM coadministered with routine vaccines did not reduce immune responses to diphtheria, tetanus, poliovirus, hepatitis B, Haemophilus influenzae type b, pneumococcal conjugate, measles-mumps-rubella, varicella or pertussis antigens. Noninferiority criteria were not met for some pneumococcal conjugate serotypes at 7 months of age, but no consistent trends were observed. In adolescents, coadministration did not reduce immune responses to tetanus, diphtheria and human papilloma virus vaccine antigens. Noninferiority criteria for pertussis antigens were not uniformly met in infant and adolescent studies, although the clinical relevance is unclear. In adults, coadministration did not reduce immune responses to hepatitis A/B, typhoid fever, yellow fever, Japanese encephalitis and rabies antigens. Immune responses to MenACWY-CRM were not impacted by coadministration of commonly administered vaccines. Coadministration did not increase frequencies of postvaccination adverse events in any age group. With no clinically relevant vaccine interactions or impact on vaccine reactogenicity or safety, these results support the coadministration of MenACWY-CRM with routine vaccines in all age groups.

  6. Colon dysregulation in methamphetamine self-administering HIV-1 transgenic rats.

    Directory of Open Access Journals (Sweden)

    Amanda L Persons

    Full Text Available The integrity and function of the gut is impaired in HIV-infected individuals, and gut pathogenesis may play a role in several HIV-associated disorders. Methamphetamine is a popular illicit drug abused by HIV-infected individuals. However, the effect of methamphetamine on the gut and its potential to exacerbate HIV-associated gut pathology is not known. To shed light on this scenario, we evaluated colon barrier pathology in a rat model of the human comorbid condition. Intestinal barrier integrity and permeability were assessed in drug-naïve Fischer 344 HIV-1 transgenic (Tg and non-Tg rats, and in Tg and non-Tg rats instrumented with jugular cannulae trained to self-administer methamphetamine or serving as saline-yoked controls. Intestinal permeability was determined by measuring the urine content of orally gavaged sugars. Intestinal barrier integrity was evaluated by immunoblotting or immunofluorescence of colon claudin-1 and zonula occludens-1 (ZO-1, two major tight junction proteins that regulate gut epithelial paracellular permeability. Both non-Tg and Tg rats self-administered moderate amounts of methamphetamine. These amounts were sufficient to increase colon permeability, reduce protein level of claudin-1, and reduce claudin-1 and ZO-1 immunofluorescence in Tg rats relative to non-Tg rats. Methamphetamine decreased tight junction immunofluorescence in non-Tg rats, with a similar, but non-significant trend observed in Tg rats. However, the effect of methamphetamine on tight junction proteins was subthreshold to gut leakiness. These findings reveal that both HIV-1 proteins and methamphetamine alter colon barrier integrity, and indicate that the gut may be a pathogenic site for these insults.

  7. Colon dysregulation in methamphetamine self-administering HIV-1 transgenic rats.

    Science.gov (United States)

    Persons, Amanda L; Bradaric, Brinda D; Dodiya, Hemraj B; Ohene-Nyako, Michael; Forsyth, Christopher B; Keshavarzian, Ali; Shaikh, Maliha; Napier, T Celeste

    2018-01-01

    The integrity and function of the gut is impaired in HIV-infected individuals, and gut pathogenesis may play a role in several HIV-associated disorders. Methamphetamine is a popular illicit drug abused by HIV-infected individuals. However, the effect of methamphetamine on the gut and its potential to exacerbate HIV-associated gut pathology is not known. To shed light on this scenario, we evaluated colon barrier pathology in a rat model of the human comorbid condition. Intestinal barrier integrity and permeability were assessed in drug-naïve Fischer 344 HIV-1 transgenic (Tg) and non-Tg rats, and in Tg and non-Tg rats instrumented with jugular cannulae trained to self-administer methamphetamine or serving as saline-yoked controls. Intestinal permeability was determined by measuring the urine content of orally gavaged sugars. Intestinal barrier integrity was evaluated by immunoblotting or immunofluorescence of colon claudin-1 and zonula occludens-1 (ZO-1), two major tight junction proteins that regulate gut epithelial paracellular permeability. Both non-Tg and Tg rats self-administered moderate amounts of methamphetamine. These amounts were sufficient to increase colon permeability, reduce protein level of claudin-1, and reduce claudin-1 and ZO-1 immunofluorescence in Tg rats relative to non-Tg rats. Methamphetamine decreased tight junction immunofluorescence in non-Tg rats, with a similar, but non-significant trend observed in Tg rats. However, the effect of methamphetamine on tight junction proteins was subthreshold to gut leakiness. These findings reveal that both HIV-1 proteins and methamphetamine alter colon barrier integrity, and indicate that the gut may be a pathogenic site for these insults.

  8. Developmental toxicity of orally administered sildenafil citrate (Viagra) in SWR/J mice.

    Science.gov (United States)

    Abou-Tarboush, Faisal Mohamed; Abdel-Samad, Mohamed Fathy; Al-Meteri, Mokhlid Hamed

    2011-04-01

    Normal adult inbred SWR/J mice were used to investigate the teratogenic and other possible toxic effects of various dose levels of sildenafil citrate (Viagra) on fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3, 4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into pregnant mice on days 7-9, 10-12 or 13-15 of gestation. On day 17 of pregnancy, all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity) and for external, internal and skeletal malformations. A total of 285 pregnant mice were used in the present study. None of the dams treated with sildenafil citrate at any of the oral dose levels used in the present study died during the experimental period and all dams treated with the drug failed to reveal overt signs of maternal toxicity. Moreover, the results of the present study clearly demonstrate that none of the multiple oral dose levels of the drug at any time interval used has induced any external, internal or skeletal malformations in the fetuses obtained from treated females. However, the dose level of 40 mg/kg body weight of sildenafil citrate has a growth suppressing effect on alive fetuses when it was administered at all the time intervals used in the present study. Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo-fetal toxicity when the drug is applied on days 13-15 of gestation. The possible mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing effects of sildenafil citrate were discussed. The results of this study have important implications for the widespread use of this drug.

  9. Crayfish Self-Administer Amphetamine in a Spatially Contingent Task

    Directory of Open Access Journals (Sweden)

    Udita Datta

    2018-05-01

    Full Text Available Natural reward is an essential element of any organism’s ability to adapt to environmental variation. Its underlying circuits and mechanisms guide the learning process as they help associate an event, or cue, with the perception of an outcome’s value. More generally, natural reward serves as the fundamental generator of all motivated behavior. Addictive plant alkaloids are able to activate this circuitry in taxa ranging from planaria to humans. With modularly organized nervous systems and confirmed vulnerabilities to human drugs of abuse, crayfish have recently emerged as a compelling model for the study of the addiction cycle, including psychostimulant effects, sensitization, withdrawal, reinstatement, and drug reward in conditioned place preference paradigms. Here we extend this work with the demonstration of a spatially contingent, operant drug self-administration paradigm for amphetamine. When the animal enters a quadrant of the arena with a particular textured substrate, a computer-based control system delivers amphetamine through an indwelling fine-bore cannula. Resulting reward strength, dose-response, and the time course of operant conditioning were assessed. Individuals experiencing the drug contingent on their behavior, displayed enhanced rates of operant responses compared to that of their yoked (non-contingent counterparts. Application of amphetamine near the supra-esophageal ganglion elicited stronger and more robust increases in operant responding than did systemic infusions. This work demonstrates automated implementation of a spatially contingent self-administration paradigm in crayfish, which provides a powerful tool to explore comparative perspectives in drug-sensitive reward, the mechanisms of learning underlying the addictive cycle, and phylogenetically conserved vulnerabilities to psychostimulant compounds.

  10. Pharmacology of ayahuasca administered in two repeated doses.

    Science.gov (United States)

    Dos Santos, Rafael G; Grasa, Eva; Valle, Marta; Ballester, Maria Rosa; Bouso, José Carlos; Nomdedéu, Josep F; Homs, Rosa; Barbanoj, Manel J; Riba, Jordi

    2012-02-01

    Ayahuasca is an Amazonian tea containing the natural psychedelic 5-HT(2A/2C/1A) agonist N,N-dimethyltryptamine (DMT). It is used in ceremonial contexts for its visionary properties. The human pharmacology of ayahuasca has been well characterized following its administration in single doses. To evaluate the human pharmacology of ayahuasca in repeated doses and assess the potential occurrence of acute tolerance or sensitization. In a double-blind, crossover, placebo-controlled clinical trial, nine experienced psychedelic drug users received PO the two following treatment combinations at least 1 week apart: (a) a lactose placebo and then, 4 h later, an ayahuasca dose; and (b) two ayahuasca doses 4 h apart. All ayahuasca doses were freeze-dried Amazonian-sourced tea encapsulated to a standardized 0.75 mg DMT/kg bodyweight. Subjective, neurophysiological, cardiovascular, autonomic, neuroendocrine, and cell immunity measures were obtained before and at regular time intervals until 12 h after first dose administration. DMT plasma concentrations, scores in subjective and neurophysiological variables, and serum prolactin and cortisol were significantly higher after two consecutive doses. When effects were standardized by plasma DMT concentrations, no differences were observed for subjective, neurophysiological, autonomic, or immunological effects. However, we observed a trend to reduced systolic blood pressure and heart rate, and a significant decrease for growth hormone (GH) after the second ayahuasca dose. Whereas there was no clear-cut tolerance or sensitization in the psychological sphere or most physiological variables, a trend to lower cardiovascular activation was observed, together with significant tolerance to GH secretion.

  11. Development of organophosphate hydrolase activity in a bacterial homolog of human cholinesterase

    Science.gov (United States)

    Legler, Patricia; Boisvert, Susanne; Compton, Jaimee; Millard, Charles

    2014-07-01

    We applied a combination of rational design and directed evolution (DE) to Bacillus subtilis p-nitrobenzyl esterase (pNBE) with the goal of enhancing organophosphorus acid anhydride hydrolase (OPAAH) activity. DE started with a designed variant, pNBE A107H, carrying a histidine homologous with human butyrylcholinesterase G117H to find complementary mutations that further enhance its OPAAH activity. Five sites were selected (G105, G106, A107, A190, and A400) within a 6.7 Å radius of the nucleophilic serine O?. All 95 variants were screened for esterase activity with a set of five substrates: pNP-acetate, pNP-butyrate, acetylthiocholine, butyrylthiocholine, or benzoylthiocholine. A microscale assay for OPAAH activity was developed for screening DE libraries. Reductions in esterase activity were generally concomitant with enhancements in OPAAH activity. One variant, A107K, showed an unexpected 7-fold increase in its kcat/Km for benzoylthiocholine, demonstrating that it is also possible to enhance the cholinesterase activity of pNBE. Moreover, DE resulted in at least three variants with modestly enhanced OPAAH activity compared to wild type pNBE. A107H/A190C showed a 50-fold increase in paraoxonase activity and underwent a slow time- and temperature-dependent change affecting the hydrolysis of OPAA and ester substrates. Structural analysis suggests that pNBE may represent a precursor leading to human cholinesterase and carboxylesterase 1 through extension of two vestigial specificity loops; a preliminary attempt to transfer the Ω-loop of BChE into pNBE is described. pNBE was tested as a surrogate scaffold for mammalian esterases. Unlike butyrylcholinesterase and pNBE, introducing a G143H mutation (equivalent to G117H) did not confer detectable OP hydrolase activity on human carboxylesterase 1. We discuss the importance of the oxyanion-hole residues for enhancing the OPAAH activity of selected serine hydrolases.

  12. Acetylcholinesterase and Butyrylcholinesterase Inhibited by Paraoxon

    Czech Academy of Sciences Publication Activity Database

    Kuča, K.; Musilová, L.; Paleček, J.; Církva, Vladimír; Paar, M.; Musílek, K.; Hrabinová, M.; Pohanka, M.; Zdarová Karasová, J.; Jun, D.

    2009-01-01

    Roč. 14, č. 12 (2009), s. 4915-4921 ISSN 1420-3049 Grant - others:MO0(CZ) FZV0000604 Institutional research plan: CEZ:AV0Z40720504 Keywords : acetylcholinesterase * reactivator * oxime Subject RIV: CC - Organic Chemistry Impact factor: 1.738, year: 2009

  13. Dose distribution to spinal structures from intrathecally administered yttrium-90

    Science.gov (United States)

    Mardirossian, George; Hall, Michael; Montebello, Joseph; Stevens, Patrick

    2006-01-01

    Previous treatment of cerebrospinal fluid (CSF) malignancies by intrathecal administration of 131I-radiolabelled monoclonal antibodies has led to the assumption that more healthy tissue will be spared when a pure beta-emitter such as 90Y replaces 131I. The purpose of this study is to compare and quantitatively evaluate the dose distribution from 90Y to the CSF space and its surrounding spinal structures to 131I. A 3D digital phantom of a section of the T-spine was constructed from the visible human project series of images which included the spinal cord, central canal, subarachnoid space, pia mater, arachnoid, dura mater, vertebral bone marrow and intervertebral disc. Monte Carlo N-particle (MCNP4C) was used to model the 90Y and 131I radiation distribution. Images of the CSF compartment were convolved with the radiation distribution to determine the dose within the subarachnoid space and surrounding tissues. 90Y appears to be a suitable radionuclide in the treatment of central nervous system (CNS) malignancies when attached to mAb's and the dose distribution would be confined largely within the vertebral foramen. This choice may offer favourable dose improvement to the subarachnoid and surface of spinal cord over 131I in such an application.

  14. Acute toxicity of intravenously administered titanium dioxide nanoparticles in mice.

    Directory of Open Access Journals (Sweden)

    Jiaying Xu

    Full Text Available BACKGROUND: With a wide range of applications, titanium dioxide (TiO₂ nanoparticles (NPs are manufactured worldwide in large quantities. Recently, in the field of nanomedicine, intravenous injection of TiO₂ nanoparticulate carriers directly into the bloodstream has raised public concerns on their toxicity to humans. METHODS: In this study, mice were injected intravenously with a single dose of TiO₂ NPs at varying dose levels (0, 140, 300, 645, or 1387 mg/kg. Animal mortality, blood biochemistry, hematology, genotoxicity and histopathology were investigated 14 days after treatment. RESULTS: Death of mice in the highest dose (1387 mg/kg group was observed at day two after TiO₂ NPs injection. At day 7, acute toxicity symptoms, such as decreased physical activity and decreased intake of food and water, were observed in the highest dose group. Hematological analysis and the micronucleus test showed no significant acute hematological or genetic toxicity except an increase in the white blood cell (WBC count among mice 645 mg/kg dose group. However, the spleen of the mice showed significantly higher tissue weight/body weight (BW coefficients, and lower liver and kidney coefficients in the TiO₂ NPs treated mice compared to control. The biochemical parameters and histological tissue sections indicated that TiO₂ NPs treatment could induce different degrees of damage in the brain, lung, spleen, liver and kidneys. However, no pathological effects were observed in the heart in TiO₂ NPs treated mice. CONCLUSIONS: Intravenous injection of TiO₂ NPs at high doses in mice could cause acute toxicity effects in the brain, lung, spleen, liver, and kidney. No significant hematological or genetic toxicity was observed.

  15. Differential effects of estradiol on carotid artery inflammation when administered early versus late after surgical menopause.

    Science.gov (United States)

    Sophonsritsuk, Areepan; Appt, Susan E; Clarkson, Thomas B; Shively, Carol A; Espeland, Mark A; Register, Thomas C

    2013-05-01

    The aim of this study was to determine the effects of estrogen therapy (ET) on carotid artery inflammation when initiated early and late relative to surgical menopause. Female cynomolgus macaques consuming atherogenic diets were ovariectomized and randomized to control or oral estradiol (E2; human equivalent dose of 1 mg/d micronized E2) initiated at 1 month (early menopause, n = 24) or 54 months (late menopause, n = 40) after ovariectomy. The treatment period was 8 months. Carotid artery expression of the markers of monocyte/macrophages (CD68 and CD163), dendritic cells (CD83), natural killer cells (neural cell adhesion molecule-1), and interferon-γ was significantly lower in E2-treated animals in the early menopause group but not in the late menopause group (P menopausal stage (P menopause inhibits macrophage accumulation in the carotid artery, an effect that is not observed when E2 is administered after several years of estrogen deficiency. No evidence for pro-inflammatory effects of late ET is observed. The results provide support for the timing hypothesis of postmenopausal ET with implications for the interpretation of outcomes in the Women's Health Initiative.

  16. Open-label, multicenter study of self-administered icatibant for attacks of hereditary angioedema

    DEFF Research Database (Denmark)

    Aberer, W; Maurer, M; Reshef, A

    2014-01-01

    Historically, treatment for hereditary angioedema (HAE) attacks has been administered by healthcare professionals (HCPs). Patient self-administration could reduce delays between symptom onset and treatment, and attack burden. The primary objective was to assess the safety of self-administered ica...

  17. 39 CFR 222.2 - Authority to administer oaths or function as notaries public.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Authority to administer oaths or function as notaries public. 222.2 Section 222.2 Postal Service UNITED STATES POSTAL SERVICE ORGANIZATION AND ADMINISTRATION DELEGATIONS OF AUTHORITY § 222.2 Authority to administer oaths or function as notaries public. (a...

  18. 40 CFR 131.8 - Requirements for Indian Tribes to administer a water quality standards program.

    Science.gov (United States)

    2010-07-01

    ... administer a water quality standards program. 131.8 Section 131.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS WATER QUALITY STANDARDS General Provisions § 131.8 Requirements for Indian Tribes to administer a water quality standards program. (a) The Regional Administrator, as...

  19. 42 CFR 2a.5 - Contents of application; research projects in which drugs will be administered.

    Science.gov (United States)

    2010-10-01

    ... application; research projects in which drugs will be administered. (a) In addition to the information... drug shall contain: (1) Identification of the drugs to be administered in the research project and a... project will be conducted. (b) An application for an authorization of confidentiality with respect to a...

  20. Nurse administered propofol sedation for pulmonary endoscopies requires a specific protocol

    DEFF Research Database (Denmark)

    Jensen, Jeppe Thue; Banning, Anne-Marie; Clementsen, Paul

    2012-01-01

    This study provides an evaluation and risk analysis of propofol sedation for endoscopic pulmonary procedures according to our unit's "gastroenterologic nurse-administered propofol sedation (NAPS) guideline".......This study provides an evaluation and risk analysis of propofol sedation for endoscopic pulmonary procedures according to our unit's "gastroenterologic nurse-administered propofol sedation (NAPS) guideline"....

  1. 40 CFR 147.1703 - EPA-administered program-Indian lands.

    Science.gov (United States)

    2010-07-01

    ... Carolina § 147.1703 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of wells on Indian lands in the State of North Carolina is administered by EPA. This program consists of... these requirements. (b) Effective date. The effective date of the UIC program for Indian lands in North...

  2. Detrimental Effects of a Self-reward Contracting Program on Subjects' Involvement in Self-administered Desensitization

    Science.gov (United States)

    Barrera, Manuel Jr.; Rosen, Gerald M.

    1977-01-01

    Assesses a self-reward contracting procedure intended to facilitate completion of self-administered desensitization. Self-referred snake phobics received either (a) self-administered desensitization; (b) self-administered desensitization with self-reward contracting; or (c) a self-administered placebo with self-reward contracting. Results show the…

  3. Distribution of rare earths in liver of mice administered with chloride compounds of 12 rare earths

    International Nuclear Information System (INIS)

    Shinohara, A.; Chiba, M.; Inaba, Y.

    1998-01-01

    Full text: Rare earths are used in high technology field, however, the information on their biological effects are not sufficient. The behaviour of rare earths in biology is of interest in connection with their toxicity. In the present study, the distribution of rare earths in liver of mice administered with these elements was investigated. The effects on Ca and other biological essential elements were also determined. Male mice (5 weeks old) were injected with one of 12 kinds of rare earths (chlorides of Y, La, Ce, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er and Yb) at the dose of 25 mg/KXg body weight. After 20 hours of administration, mice were sacrificed, then liver and other organs were taken out. Liver was homogenized and separated by centrifugation. The concentrations of rare earths administered were measured by microwave-induced plasma-mass spectrometry (MIP-MS) after acid digestion. The concentrations of administered elements in whole liver were about 100μg/g (wet weight), where the difference between elements was few. Distribution amounts of elements administered in four fractions were following order; 700μg precipitate > mitocondrial fraction > microsomal fraction > cytosol. The relative contents in these fractions, however, was different depending on the element administered. Calcium concentrations in liver of administered mice were higher than those of control mice. Increase of Ca concentrations were observed in all four fractions and the increase ratio was also dependent on the elements administered

  4. Pharmacokinetics of the injectable formulation of methadone hydrochloride administered orally in horses.

    Science.gov (United States)

    Linardi, R L; Stokes, A M; Barker, S A; Short, C; Hosgood, G; Natalini, C C

    2009-10-01

    Methadone hydrochloride is a synthetic mu-opioid receptor agonist with potent analgesic properties. Oral methadone has been successfully used in human medicine and may overcome some limitations of other analgesics in equine species for producing analgesia with minimal adverse effects. However, there are no studies describing the pharmacokinetics (PK) of oral opioids in horses. The aim of this study was to describe the PK of orally administered methadone (0.1, 0.2 and 0.4 mg/kg) and physical effects in 12 healthy adult horses. Serum methadone concentrations were measured by gas chromatography/mass spectrometry at predetermined time points for 24 h, and PK parameters were estimated using a noncompartmental model. Physical effects were observed and recorded by experienced clinicians. No drug toxicity, behavioural or adverse effects were observed in the horses. The disposition of methadone followed first order elimination and a biphasic serum profile with rapid absorption and elimination phases. The PK profile of methadone was characterized by high clearance (Cl/F), small volume of distribution (V(d)/F) and short elimination half-life (t(1/2)). The mean of the estimated t(1/2) (SD) for each dose (0.1, 0.2 and 0.4 mg/kg) was 2.2 (35.6), 1.3 (46.1) and 1.5 (40.8), and the mean for the estimated C(max) (SD) was 33.9 (6.7), 127.9 (36.0) and 193.5 (65.8) respectively.

  5. Discriminative stimulus properties of intragastrically administered d-amphetamine and pentobarbital in rhesus monkeys.

    Science.gov (United States)

    de la Garza, R; Johanson, C E

    1987-12-01

    Rhesus monkeys were trained to discriminate intragastrically administered d-amphetamine (AMPH) or pentobarbital (PENTO) from saline using a signaled shock-avoidance trail procedure. All monkeys maintained criterion levels (greater than 90% drug-appropriate responding) throughout the duration of the study during training sessions. In the AMPH experiment, the anorectics diethylpropion, mazindol, phendimetrazine, phenmetrazine and phentermine completely substituted for the training dose of AMPH. The atypical antidepressant bupropion and the psychomotor stimulant methylphenidate also completely substituted for AMPH. Other anorectics including benzphetamine, clortermine, fenetylline, mefenorex and the psychomotor stimulant pemoline that share some pharmacological properties with AMPH substituted for AMPH in some, but not all, of the monkeys tested. The anorectics fenfluramine and chlorphentermine failed to substitute for AMPH. Drugs from other pharmacological classes such as morphine, diazepam, nortripyline and PENTO also failed to substitute for AMPH, indicating pharmacological specificity. In the PENTO experiment, the benzodiazepines alprazolam, bromazepam, diazepam, flurazepam, halazepam, lorazepam, midazolam, oxazepam, temazepam and triazolam and the sedatives methaqualone and phenobarbital completely substituted for the training dose of PENTO. The nonbenzodiazepine anxiolytic CL 218,872 only partially substituted for PENTO. In addition, morphine and AMPH failed to substitute for PENTO, indicating pharmacological specificity. In summary, drugs delivered intragastrically functioned as discriminative stimuli in a drug-class specific manner. The ability to use drugs delivered by this route as discriminative stimuli provides a way to compare anorectic drugs to AMPH or sedative drugs to PENTO under conditions that resemble the mode of human consumption to determine whether these drugs are likely to be associated with AMPH-like or PENTO-like drug dependence.

  6. ASA24 enables multiple automatically coded self-administered 24-hour recalls and food records

    Science.gov (United States)

    A freely available web-based tool for epidemiologic, interventional, behavioral, or clinical research from NCI that enables multiple automatically coded self-administered 24-hour recalls and food records.

  7. Intravenously administered lidocaine in therapeutic doses increases the intraspinal release of acetylcholine in rats

    DEFF Research Database (Denmark)

    Abelson, Klas S P; Höglund, A Urban

    2002-01-01

    The local anesthetic lidocaine suppresses different pain conditions when administered systemically. Part of the antinociceptive effect appears to be mediated via receptor mechanisms. We have previously shown that muscarinic and nicotinic agonists that produce antinociception increase the intraspi...

  8. Administrator of 9/11 victim compensation fund to administer Hokie Spirit Memorial Fund distributions

    OpenAIRE

    Hincker, Lawrence

    2007-01-01

    Virginia Tech President Charles Steger has asked Kenneth R. Feinberg, who served as "Special Master of the federal September 11th Victim Compensation Fund of 2001," to administer distributions of the university Hokie Spirit Memorial Fund (HSMF).

  9. Proinflammatory effects of exogenously administered IL-10 in experimental autoimmune orchitis

    DEFF Research Database (Denmark)

    Kaneko, Tetsushi; Itoh, Masahiro; Nakamura, Yoichi

    2003-01-01

    We studied the effects of exogenously administered recombinant murine interleukin (IL)-10 on the development of experimental autoimmune orchitis (EAO) in C3H/He mice. IL-10 significantly augments histological signs of EAO when administered for 6 consecutive days from days 15 to 20 after primary...... immunisations with testicular germ cells. These data demonstrate that IL-10, in addition to its well-known antiinflammatory property, also has proinflammatory functions capable of up-regulating testicular immunoinflammatory processes in vivo....

  10. Acute Chloroform Ingestion Successfully Treated with Intravenously Administered N-acetylcysteine

    OpenAIRE

    Dell’Aglio, Damon M.; Sutter, Mark E.; Schwartz, Michael D.; Koch, David D.; Algren, D. A.; Morgan, Brent W.

    2010-01-01

    Chloroform, a halogenated hydrocarbon, causes central nervous system depression, cardiac arrhythmias, and hepatotoxicity. We describe a case of chloroform ingestion with a confirmatory serum level and resultant hepatotoxicity successfully treated with intravenously administered N-acetylcysteine (NAC). A 19-year-old man attempting suicide ingested approximately 75 mL of chloroform. He was unresponsive and intubated upon arrival. Intravenously administered NAC was started after initial stabiliz...

  11. Current role of non-anesthesiologist administered propofol sedation in advanced interventional endoscopy

    DEFF Research Database (Denmark)

    Burtea, Daniela Elena; Dimitriu, Anca; Maloş, Anca Elena

    2015-01-01

    the patients and medical personnel. Current guidelines support the use of propofol sedation, which has the same rate of adverse effects as traditional sedation with benzodiazepines and/or opioids, but decreases the procedural and recovery time. Non-anesthesiologist administered propofol sedation has become......, improved satisfaction for patients and doctors, as well as decreased recovery and discharge time. Despite the advantages of non-anesthesiologist administered propofol, there is still a continuous debate related to the successful generalization of the procedures....

  12. Hemato-biochemical responses to packing in donkeys administered ascorbic acid during the harmattan season

    OpenAIRE

    OLAIFA, Folashade; AYO, Joseph Olusegun; AMBALI, Suleiman Folorunsho; REKWOT, Peter Ibrahim

    2012-01-01

    Experiments were performed to investigate the effect of ascorbic acid (AA) in reducing hemato-biochemical changes in pack donkeys during the cold-dry (harmattan) season. Six experimental donkeys administered orally AA (200 mg/kg) and six control donkeys not administered ascorbic acid were subjected to packing. Blood samples were collected from all donkeys for hematological and biochemical analyses. In the control donkeys, packed cell volume (PCV), erythrocyte count and hemoglobin concentratio...

  13. Accelerating cocaine metabolism as an approach to the treatment of cocaine abuse and toxicity

    Science.gov (United States)

    Schindler, Charles W; Goldberg, Steven R

    2012-01-01

    One pharmacokinetic approach to the treatment of cocaine abuse and toxicity involves the development of compounds that can be safely administered to humans and that accelerate the metabolism of cocaine to inactive components. Catalytic antibodies have been developed and shown to accelerate cocaine metabolism, but their catalytic efficiency for cocaine is relatively low. Mutations of human butyrylcholinesterase and a bacterial cocaine esterase found in the soil of coca plants have also been developed. These compounds accelerate cocaine metabolism and antagonize the behavioral and toxic effects of cocaine in animal models. Of these two approaches, the human butyrylcholinesterase mutants show the most immediate promise as they would not be expected to evoke an immune response in humans. PMID:22300096

  14. Validation of a self-administered questionnaire for assessing occupational and environmental exposures of pregnant women

    International Nuclear Information System (INIS)

    Eskenazi, B.; Pearson, K.

    1988-01-01

    The present investigation sought to determine whether a self-administered questionnaire could be used to obtain occupational information from pregnant women attending the obstetrical clinics at the University of California, San Francisco from July to November 1986. The authors compared the accuracy of responses of 57 women on the self-administered questionnaire with those obtained on a detailed clinical interview by an occupational health professional. The self-administered questionnaire and the clinical interview included information on the woman's job title, the type of company she worked for, the level of physical activity, her exposures on the job and at home, and her partner's occupation. The authors also examined whether the validity of the self-administered questionnaire could be improved on review by an industrial hygienist. The questionnaire took less than 20 minutes to complete, with over 90% of the women answering three-quarters of it. It was substantially accurate in obtaining information on number of hours worked during pregnancy, type of shift worked, and stress level in the workplace; exposure to radiation, video display terminals, fumes, gases, and cigarette smoke in the workplace; and exposure to pesticides, paint, and cigarette smoke at home. On those variables for which the responses on the self-administered questionnaire were less accurate, review by the industrial hygienist improved the level of accuracy considerably. These findings suggest that a self-administered questionnaire can be used to obtain valid information from pregnant women attending a prenatal clinic

  15. MECHANISMS IN ENDOCRINOLOGY: Exogenous insulin does not increase muscle protein synthesis rate when administered systemically: a systematic review.

    Science.gov (United States)

    Trommelen, Jorn; Groen, Bart B L; Hamer, Henrike M; de Groot, Lisette C P G M; van Loon, Luc J C

    2015-07-01

    Though it is well appreciated that insulin plays an important role in the regulation of muscle protein metabolism, there is much discrepancy in the literature on the capacity of exogenous insulin administration to increase muscle protein synthesis rates in vivo in humans. To assess whether exogenous insulin administration increases muscle protein synthesis rates in young and older adults. A systematic review of clinical trials was performed and the presence or absence of an increase in muscle protein synthesis rate was reported for each individual study arm. In a stepwise manner, multiple models were constructed that excluded study arms based on the following conditions: model 1, concurrent hyperaminoacidemia; model 2, insulin-induced hypoaminoacidemia; model 3, supraphysiological insulin concentrations; and model 4, older, more insulin resistant, subjects. From the presented data in the current systematic review, we conclude that: i) exogenous insulin and amino acid administration effectively increase muscle protein synthesis, but this effect is attributed to the hyperaminoacidemia; ii) exogenous insulin administered systemically induces hypoaminoacidemia which obviates any insulin-stimulatory effect on muscle protein synthesis; iii) exogenous insulin resulting in supraphysiological insulin levels exceeding 50, 000  pmol/l may effectively augment muscle protein synthesis; iv) exogenous insulin may have a diminished effect on muscle protein synthesis in older adults due to age-related anabolic resistance; and v) exogenous insulin administered systemically does not increase muscle protein synthesis in healthy, young adults. © 2015 European Society of Endocrinology.

  16. Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications

    Directory of Open Access Journals (Sweden)

    Shen J

    2017-09-01

    Full Text Available Jie Shen,1 Margot L Goodkin,2 Warren Tong,2 Mayssa Attar3 1Clinical Pharmacology, 2Clinical Development, 3Clinical Pharmacology, Metabolism and Immunology, Allergan plc, Irvine, CA, USA Purpose: Fixed-combination medications can benefit patients requiring multiple agents to lower their intraocular pressure (IOP, but combining agents with complementary mechanisms of action is challenging if their dosing frequency differs. This study compares in vivo pharmacokinetic and ocular tolerability of bimatoprost 0.01% ophthalmic solutions dosed once or twice daily. Reports of twice-daily dosing in glaucoma patients are also reviewed.Methods: New Zealand White rabbits were administered bimatoprost 0.01% monotherapy or fixed-combination bimatoprost 0.01%/brimonidine 0.1%, once or twice daily in both eyes for 4 days. Ocular tissues were harvested and analyzed by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters calculated included maximum observed concentration, time to maximum concentration, and area under the concentration-time curve.Results: Due to extensive metabolism, bimatoprost concentration was below the quantitation limit by 1 hour post-dose in all samples. Bimatoprost acid exposure, however, could be measured up to 6–8 hours post-dose and was similar in the aqueous humor and iris-ciliary body (pharmacological site of action of animals treated once or twice daily with either bimatoprost 0.01% or fixed-combination bimatoprost 0.01%/brimonidine 0.1%. Increasing dosage frequency in rabbits did not raise the incidence of drug-related conjunctival hyperemia (most common adverse event associated with bimatoprost use in humans, suggesting comparable ocular tolerability of the once- and twice-daily regimens for each formulation.Conclusion: Bimatoprost 0.01% administered once or twice daily as monotherapy and in fixed-combination with brimonidine 0.1% in rabbits show similar pharmacokinetic profiles of bimatoprost acid

  17. Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications

    Science.gov (United States)

    Shen, Jie; Goodkin, Margot L; Tong, Warren; Attar, Mayssa

    2017-01-01

    Purpose Fixed-combination medications can benefit patients requiring multiple agents to lower their intraocular pressure (IOP), but combining agents with complementary mechanisms of action is challenging if their dosing frequency differs. This study compares in vivo pharmacokinetic and ocular tolerability of bimatoprost 0.01% ophthalmic solutions dosed once or twice daily. Reports of twice-daily dosing in glaucoma patients are also reviewed. Methods New Zealand White rabbits were administered bimatoprost 0.01% monotherapy or fixed-combination bimatoprost 0.01%/brimonidine 0.1%, once or twice daily in both eyes for 4 days. Ocular tissues were harvested and analyzed by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters calculated included maximum observed concentration, time to maximum concentration, and area under the concentration-time curve. Results Due to extensive metabolism, bimatoprost concentration was below the quantitation limit by 1 hour post-dose in all samples. Bimatoprost acid exposure, however, could be measured up to 6–8 hours post-dose and was similar in the aqueous humor and iris-ciliary body (pharmacological site of action) of animals treated once or twice daily with either bimatoprost 0.01% or fixed-combination bimatoprost 0.01%/brimonidine 0.1%. Increasing dosage frequency in rabbits did not raise the incidence of drug-related conjunctival hyperemia (most common adverse event associated with bimatoprost use in humans), suggesting comparable ocular tolerability of the once- and twice-daily regimens for each formulation. Conclusion Bimatoprost 0.01% administered once or twice daily as monotherapy and in fixed-combination with brimonidine 0.1% in rabbits show similar pharmacokinetic profiles of bimatoprost acid, especially in the iris-ciliary body. Key findings from previous clinical studies suggest that by varying the concentration of benzalkonium chloride (a preservative with corneal penetration-enhancing properties

  18. [The estimation of systemic chemotherapy treatment administered in breast cancer on lysozyme activity in tears--preliminary report].

    Science.gov (United States)

    Wojciechowska, Katarzyna; Jurowski, Piotr; Wieckowska-Szakiel, Marzena; Rózalska, Barbara

    2012-01-01

    Estimation of cytostatics influence used in breast cancer treatment on lysozyme activity in human tears depend on time of treatment. 8 women were treated at the base of chemotherapy schema: docetaxel with doxorubicin and 4 women treated with schema CMF: cyclophosphamide, methotrexate, 5-fluorouracil. Lysozyme activity in tears was assessed by measurement of diameter zone of Micrococcus lysodeicticus growth inhibition. It was revealed that both chemotherapy schema caused statistically significant reduction of diameter zone of M. lysodeicticus growth inhibition, after first and second course of chemotherapy treatment. After second chemotherapy course CMF schema induced loss of lysozyme activity in patient's tears (zero mm of M. lysodeicticus diameter zone growth inhibition). Systemic chemotherapy administered in breast cancer induce reduction of lysozyme activity in tears, that may cause higher morbidity of ocular surface infections caused by Gram-positive bacteria.

  19. [Clinical outcomes of parenterally administered shuxuetong--analysis of hospital information system data].

    Science.gov (United States)

    Zhi, Ying-Jie; Zhang, Hui; Xie, Yan-Ming; Yang, Wei; Yang, Hu; Zhuang, Yan

    2013-09-01

    Hospital information system data of cerebral infaction patients who received parenterally administered Shuxuetong was analyzed. This provided frequency data regarding patients' conditions and related information in order to provide a clinical reference guide. In this study, HIS data from 18 hospitals was analyzed. Patients receiving parenterally administered Shuxuetong for the treatment of cerebral infarction were included. Information on age, gender, costsand route of administration were collated. The average age of patients was 66 years old. Days of hospitalization ranged from 15 to 28 days. The majority of patients were classified as having phlegm and blood stasis syndrome, which is inaccordance with the indications for this drug. The most commonly used drugs used in combination with parenterally administered Shuxuetong were: aspirin, insulin and heparin. Patients with cerebral infarction crowd using parenterally administered Shuxuetong were a mostly elderly population, with an average age of 66. Although generally use was in accordance with indications, dosage, and route of administration, there were however some discrepancies. Therefore, doctors need to pay close attention to guidelines and closely observe patients when using parenterally administered Shuxuetong and to consider both the clinical benefits and risks.

  20. Can we safely administer the recommended dose of phenobarbital in very low birth weight infants?

    Science.gov (United States)

    Oztekin, Osman; Kalay, Salih; Tezel, Gonul; Akcakus, Mustafa; Oygur, Nihal

    2013-08-01

    We investigated whether the recommended phenobarbital loading dose of 15-20 mg/kg with maintenance of 3-4 mg/kg/day can safely be administered to very low birth weight preterm newborns with seizures. Twenty-four convulsive preterms of Phenobarbital was administered intravenously with a loading dose of 15 mg/kg in approximately 10-15 min. After 24 h, the maintenance dose of 3 mg/kg/day was administered as a single injection. Blood samples were obtained 2, 24, 48, 72, and 96 h after the phenobarbital loading dose was administered, immediately before the next phenobarbital dose was injected. None of the cases had plasma phenobarbital concentrations above the therapeutic upper limit of 40 μg/mL on the 2nd hour; one case (4.7%), on the 24th; 11 cases (45.8%), on the 48th; 15 cases (62.5%), on the 72nd; and 17 cases (70.8%), on the 96th hour. A negative correlation was detected between the serum concentrations of phenobarbital and gestational age on the 72th (p, 0.036; r, -0.608) and 96th hour (p, 0.043; r, -0.769). We suggest that particular attention should be done while administering phenobarbital in preterms, as blood levels of phenobarbital are higher than the reference ranges that those are often reached with the recommended doses in these groups of babies.

  1. A cross-cultural validation of the Clinician Administered PTSD Scale for Children and Adolescents in a Dutch population

    NARCIS (Netherlands)

    Diehle, Julia; de Roos, Carlijn; Boer, Frits; Lindauer, Ramón J. L.

    2013-01-01

    Background: Trauma-focused interventions for children could be administered more efficiently and effectively if posttraumatic stress disorder (PTSD) and related symptoms were first investigated by a reliable and valid instrument. The Clinician Administered PTSD Scale for Children and Adolescents

  2. Even ‘safe’ medications need to be administered with care

    Science.gov (United States)

    Lutwak, Nancy; Howland, Mary Ann; Gambetta, Rosemarie; Dill, Curt

    2013-01-01

    A 60-year-old man with a history of hepatic cirrhosis and cardiomyopathy underwent transoesophageal echocardiogram. He received mild sedation and topical lidocaine. During the recovery period the patient developed ataxia and diplopia for about 30 mins, a result of lidocaine toxicity. The patient was administered a commonly used local anaesthetic, a combination of 2% viscous lidocaine, 4% lidocaine gargle and 5% lidocaine ointment topically to the oropharnyx. The total dose was at least 280 mg. Oral lidocaine undergoes extensive first pass metabolism and its clearance is quite dependent on rates of liver blood flow as well as other factors. The patient's central nervous system symptoms were mild and transient but remind us that to avoid adverse side effects, orally administered drugs with fairly high hepatic extraction ratio given to patients with chronic liver disease need to be given in reduced dosages. Even ‘Safe’ medications need to be carefully administered. PMID:23283606

  3. Disclosure of sensitive behaviors across self-administered survey modes: a meta-analysis.

    Science.gov (United States)

    Gnambs, Timo; Kaspar, Kai

    2015-12-01

    In surveys, individuals tend to misreport behaviors that are in contrast to prevalent social norms or regulations. Several design features of the survey procedure have been suggested to counteract this problem; particularly, computerized surveys are supposed to elicit more truthful responding. This assumption was tested in a meta-analysis of survey experiments reporting 460 effect sizes (total N =125,672). Self-reported prevalence rates of several sensitive behaviors for which motivated misreporting has been frequently observed were compared across self-administered paper-and-pencil versus computerized surveys. The results revealed that computerized surveys led to significantly more reporting of socially undesirable behaviors than comparable surveys administered on paper. This effect was strongest for highly sensitive behaviors and surveys administered individually to respondents. Moderator analyses did not identify interviewer effects or benefits of audio-enhanced computer surveys. The meta-analysis highlighted the advantages of computerized survey modes for the assessment of sensitive topics.

  4. Effect of tubing on loss of clonazepam administered by continuous subcutaneous infusion.

    Science.gov (United States)

    Schneider, Jennifer J; Good, Phillip; Ravenscroft, Peter J

    2006-06-01

    Previous studies have reported loss of clonazepam from solutions administered intravenously from plastic infusion bags and administration sets. In palliative care, clonazepam is sometimes administered through syringe drivers using polyvinyl chloride (PVC) infusion tubing. No data currently exist to show whether use of PVC tubing affects the amount of clonazepam actually received by the patient. This study compared the use of two different types of PVC tubing with a non-PVC tubing. Solutions containing clonazepam or clonazepam and morphine were prepared with either normal saline or water for injection as diluent. Concentrations of morphine and clonazepam were determined using high-performance liquid chromatography. Significant loss of clonazepam (up to 50%) was observed in all solutions infused through PVC tubing. Solutions infused through non-PVC tubing retained greater than 90% of the initial concentration of clonazepam. It is recommended that when administering clonazepam using a syringe driver, non-PVC tubing be used.

  5. Assessment of the sedative effects of buprenorphine administered with 20 microg/kg detomidine in horses.

    Science.gov (United States)

    Love, E J; Taylor, P M; Murrell, J; Whay, H R; Waterman-Pearson, A E

    2011-04-16

    The aim of this randomised, observer-blinded, crossover study was to compare the effects of four treatments, administered intravenously to six horses: saline and saline; 10 µg/kg detomidine and 7.5 µg/kg buprenorphine; 20 µg/kg detomidine and 7.5 µg/kg buprenorphine; and 20 µg/kg detomidine and 10 µg/kg buprenorphine. Sedation was subjectively assessed and recorded on a visual analogue scale. Peak sedation and duration of sedation were investigated using a univariate general linear model with post-hoc Tukey tests (Pdetomidine from 10 to 20 µg/kg increased the degree of sedation when administered with the same dose of buprenorphine (7.5 µg/kg). When administered with 20 µg/kg detomidine, increasing the dose of buprenorphine from 7.5 to 10 µg/kg did not influence the degree of sedation achieved.

  6. TECHNOLOGY FOR ADMINISTERING OF THE ACCESS TO INFORMATION RESOURCES IN MANAGEMENT SYSTEM ON THE AVIATION ENTERPRISE

    Directory of Open Access Journals (Sweden)

    Andrey V. Degtyarev

    2015-01-01

    Full Text Available The task of administering software-information complex occurs duringthe development of application systems for managing business-processes and is connected with the organization of access forusers to information resources in conditions of multi-user information systems for management. For solution of this problem proposed theapproach, which is based on a hierarchical system of access rightsto information resources on the levels: tool, object and procedural.Keywords: software-information complex, information resources,administering, permissions, separation of powers, access model.

  7. Knee Injury and Osteoarthritis Outcome Score (KOOS)--development of a self-administered outcome measure

    DEFF Research Database (Denmark)

    Roos, Ewa M.; Roos, H P; Lohmander, L S

    1998-01-01

    There is broad consensus that good outcome measures are needed to distinguish interventions that are effective from those that are not. This task requires standardized, patient-centered measures that can be administered at a low cost. We developed a questionnaire to assess short- and long......-term patient-relevant outcomes following knee injury, based on the WOMAC Osteoarthritis Index, a literature review, an expert panel, and a pilot study. The Knee injury and Osteoarthritis Outcome Score (KOOS) is self-administered and assesses five outcomes: pain, symptoms, activities of daily living, sport...

  8. Patient protection in nuclear medicine due to optimization of the administered activity

    International Nuclear Information System (INIS)

    Perez Diaz, M.; Diaz Rizo, O.; Khouri, H. J.

    2011-01-01

    The possibility of a radiological risk reduction in Nuclear Medicine patients is studied through the reduced absorbed doses in organs and tissues, and whole-body effective dose due to optimization of the administered radionuclide activities. Activity values, optimized for equipments and radiopharmaceuticals available in Cuba, are compared with the IAEA recommended values and with the routinary activities in medical practice. All doses were calculated using MIRDOSE 3.0 code for each activity and medical assay. The activity optimization permits to reduce in a 50% the doses administered to patients of the major part of studied medical assays. (Author)

  9. Single-dose and steady-state pharmacokinetics of diltiazem administered in two different tablet formulations

    DEFF Research Database (Denmark)

    Christrup, Lona Louring; Bonde, J; Rasmussen, S N

    1992-01-01

    Single-dose and steady state pharmacokinetics of diltiazem administered in two different oral formulations were assessed with particular reference to rate and extent of absorption. Following single dose administration a significant difference in tmax was observed (2.9 +/- 1.9 and 6.8 +/- 2.6 hr r...

  10. 20 CFR 408.1220 - How do we pay Federally administered State recognition payments?

    Science.gov (United States)

    2010-04-01

    ... recognition payments? 408.1220 Section 408.1220 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Federal Administration of State Recognition Payments § 408.1220 How do we pay Federally administered State recognition payments? (a) Payment procedures. We make...

  11. 20 CFR 1.6 - How were many of OWCP's current functions administered in the past?

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false How were many of OWCP's current functions administered in the past? 1.6 Section 1.6 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ORGANIZATION AND PROCEDURES PERFORMANCE OF FUNCTIONS § 1.6 How were many of OWCP's...

  12. Psychomotor and Motor Speed in Power Athletes Self-Administering Testosterone and Anabolic Steroids.

    Science.gov (United States)

    Era, Pertti; And Others

    1988-01-01

    Self-administered testosterone and anabolic steroids resulted in insignificant improvement in psychomotor and motor speed tests of power athletes. This study is part of a larger study on the effects of such drugs on endocrinology, metabolism and neuromuscular functions. Methodolgy and results are discussed. (Author/JL)

  13. No increased risk of perforation during colonoscopy in patients undergoing Nurse Administered Propofol Sedation

    DEFF Research Database (Denmark)

    Okholm, Cecilie; Hadikhadem, Talie; Andersen, Lærke Toftegård

    2013-01-01

    Abstract Objective. Nurse Administered Propofol Sedation (NAPS) contributes to a deeper sedation of the patients, making them unable to respond to pain and an increased incidence of perforations has been speculated. The objective of this study was to evaluate the risk of perforations during...

  14. [COOP/WONCA: Reliability and validity of the test administered by telephone].

    Science.gov (United States)

    Pedrero-Pérez, Eduardo J; Díaz-Olalla, José Manuel

    2016-01-01

    The COOP/WONCA test was initially proposed as a self-report in which the answers were supported by drawings illustrating the state investigated. Subsequent studies have confirmed its usefulness as a mere verbal self-report face-to-face administered. No data have been found about its useful when administered by telephone interview. The aim of this study was to determine the psychometric properties of the COOP / WONCA test to measure Related Quality of Life (HRQoL) administered by telephone and compare them with those obtained in other forms of prior administration. Cross-sectional study on a random. City of Madrid. Random sample of 802 adult subjects, representative of the adult population in Madrid, obtained by stratification from the population census. Questionnaire COOP/WONCA with 9 ítems included in a broader battery, administered by telephone interview. The unrestricted factor analysis points to the unifactoriality of the scale, which measures a single latent construct (HRQOL), showing high internal consistency, not significantly different from those found by face-to-face administration, ruling out the existence of biases in the phone modality. The COOP/WONCA test appears as a reliable and valid measure of HRQOL and telephonic administration allows to assume no changes in the results, which can reduce costs in population studies, increasing efficiency without loss of quality in the information collected. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  15. 41 CFR 302-14.100 - How should we administer our home marketing incentive payment program?

    Science.gov (United States)

    2010-07-01

    ... reduce your overall relocation costs. You must not make a home marketing incentive payment that exceeds... our home marketing incentive payment program? 302-14.100 Section 302-14.100 Public Contracts and... 14-HOME MARKETING INCENTIVE PAYMENTS Agency Responsibilities § 302-14.100 How should we administer...

  16. Effect of orally administered sodium bicarbonate on caecal pH.

    Science.gov (United States)

    Taylor, E A; Beard, W L; Douthit, T; Pohlman, L

    2014-03-01

    Caecal acidosis is a central event in the metabolic cascade that occurs following grain overload. Buffering the caecal acidosis by enterally administered sodium bicarbonate (NaHCO3 ) may be beneficial to affected horses. To determine the effect and duration of enterally administered NaHCO3 on caecal pH in healthy horses. Experimental study using horses with caecal cannulas. Nine horses had been previously fitted with a caecal cannula. Six horses received 1.0 g/kg bwt NaHCO3 and 3 control horses were given 3 l of water via nasogastric tube. Clinical parameters, water consumption, venous blood gases, caecal pH, faecal pH and faecal water content were measured at 6 h intervals over a 36 h study period. Horses that received enterally administered NaHCO3 had significantly increased caecal pH that lasted the duration of the study. Treated horses increased their water intake, and developed metabolic alkalaemia, significantly increased plasma sodium concentrations and significantly decreased plasma potassium concentrations. Enterally administered NaHCO3 may be beneficial in buffering caecal acidosis. © 2013 EVJ Ltd.

  17. 76 FR 22412 - Fellowship Placement Pilot Program Requests for Expressions of Interests To Administer Pilot...

    Science.gov (United States)

    2011-04-21

    ... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [Docket No. FR-5514-C-02] Fellowship Placement Pilot Program Requests for Expressions of Interests To Administer Pilot Contact Information Correction AGENCY... published a notice announcing HUD's proposal to conduct a Fellowship Placement Pilot (fellowship program...

  18. 40 CFR 147.2201 - State-administered program-Class II wells

    Science.gov (United States)

    2010-07-01

    ... Application to Oil, Gas, and Geothermal Resource Operations, sections .051.02.02.000 to .051.02.02.080... wells 147.2201 Section 147.2201 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Texas § 147.2201 State-administered program—Class II wells The UIC program for Class II wells in the...

  19. Identifying Children at Risk for Language Impairment or Dyslexia with Group-Administered Measures

    Science.gov (United States)

    Adlof, Suzanne M.; Scoggins, Joanna; Brazendale, Allison; Babb, Spencer; Petscher, Yaacov

    2017-01-01

    Purpose: The study aims to determine whether brief, group-administered screening measures can reliably identify second-grade children at risk for language impairment (LI) or dyslexia and to examine the degree to which parents of affected children were aware of their children's difficulties. Method: Participants (N = 381) completed screening tasks…

  20. 43 CFR 420.25 - Reclamation lands administered by other agencies.

    Science.gov (United States)

    2010-10-01

    ... for management of Reclamation lands for recreation purposes. Specifically: (1) Reclamation lands managed by the National Park Service, the Bureau of Sport Fisheries and Wildlife, the Bureau of Land Management, the Forest Service, and other Federal agencies will be administered in accordance with...

  1. Development and validation of a self-administered Food Allergy Quality of Life Questionnaire for children

    NARCIS (Netherlands)

    Flokstra-de Blok, B. M. J.; DunnGalvin, A.; Vlieg - Boerstra, B. J.; Oude Elberink, J. N. G.; Duiverman, E. J.; Hourihane, J. O'B.; Dubois, A. E. J.

    Having a food allergy may affect health-related quality of life (HRQL). Currently, no validated, self-administered, disease-specific HRQL questionnaire exists for children with food allergy. The aim of this study was to develop and validate the Food Allergy Quality of Life Questionnaire - Child Form

  2. 32 CFR 37.120 - Can my organization award or administer TIAs?

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Can my organization award or administer TIAs? 37.120 Section 37.120 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS General § 37.120 Can my organization award...

  3. 78 FR 23777 - Notice of Proposed Information Collection: Comment Request: HUD-Administered Small Cities Program...

    Science.gov (United States)

    2013-04-22

    ... Information Collection: Comment Request: HUD- Administered Small Cities Program Performance Assessment Report... program provides HUD with financial and physical development status of each activity funded. These reports[email protected] fax: 202-395-5806. FOR FURTHER INFORMATION CONTACT: Colette Pollard, Reports...

  4. Stress Management for Special Educators: The Self-Administered Tool for Awareness and Relaxation (STAR)

    Science.gov (United States)

    Williams, Krista; Poel, Elissa Wolfe

    2006-01-01

    The Self-Administered Tool for Awareness and Relaxation (STAR) is a stress management strategy designed to facilitate awareness of the physical, mental, emotional, and physiological effects of stress through the interconnectedness of the brain, body, and emotions. The purpose of this article is to present a stress-management model for teachers,…

  5. Efficacy of recombinant factor VIIa administered by continuous infusion to haemophilia patients with inhibitors

    NARCIS (Netherlands)

    Mauser-Bunschoten, EP; Koopman, MMW; Goede-Bolder, ADE; Leebeek, FWG; Van der Meer, J; Kooij, GMV; Van der Linden, PWG

    We have prospectively monitored treatment of haemophilia patients with inhibitors by recombinant factor VIIa (rFVIIa) administered by continuous infusion to obtain more insight in the underlying factors of the clinical efficacy of this administration method. At present, 43 treatment episodes of 14

  6. Safety and efficiency of prehospital pain management with fentanyl administered by emergency medical technicians

    DEFF Research Database (Denmark)

    Nielsen, Niels Dalsgaard; Brogaard, Kjeld; Dahl, Michael

    2007-01-01

    minor, and were not treated with naloxone.   Conclusions: Our results suggest that non-medical personnel safely can administer IV fentanyl to selected groups of patients with a satisfactory result in terms of a considerable reduction in pain score and an acceptable rate of negative coincident events....

  7. 40 CFR 147.2051 - EPA-administered program-Indian lands.

    Science.gov (United States)

    2010-07-01

    ... Carolina § 147.2051 EPA-administered program—Indian lands. (a) Contents. The UIC program for all classes of... these requirements. (b) Effective date. The effective date of the UIC program for Indian lands in South Carolina is November 25, 1988. [53 FR 43090, Oct. 25, 1988, as amended at 56 FR 9419, Mar. 6, 1991] ...

  8. Development and validation of the self-administered Food Allergy Quality of Life Questionnaire for adolescents

    NARCIS (Netherlands)

    Flokstra-de Blok, Bertine M. J.; DunnGalvin, Audrey; Vlieg-Boerstra, Berber J.; Oude Elberink, Joanne N. G.; Duiverman, Eric J.; Hourihane, Jonathan O.'Brien; Dubois, Anthony E. J.

    2008-01-01

    Food allergy can affect health-related quality of life (HRQL). Currently, no validated, self-administered, disease-specific HRQL questionnaire for adolescents with food allergy exists. We sought to develop and validate the Food Allergy Quality of Life Questionnaire-Teenager Form (FAQLQ-TF) in the

  9. Development and validation of a self-administered Food Allergy Quality of Life Questionnaire for children

    NARCIS (Netherlands)

    Flokstra-de Blok, B. M. J.; DunnGalvin, A.; Vlieg-Boerstra, B. J.; Oude Elberink, J. N. G.; Duiverman, E. J.; Hourihane, J. O.'B.; Dubois, A. E. J.

    2009-01-01

    Having a food allergy may affect health-related quality of life (HRQL). Currently, no validated, self-administered, disease-specific HRQL questionnaire exists for children with food allergy. The aim of this study was to develop and validate the Food Allergy Quality of Life Questionnaire--Child Form

  10. Treatment of enuresis risoria in children by self-administered electric and imaginary shock

    NARCIS (Netherlands)

    Elzinga-Plomp, A.; Boemers, T. M.; Messer, A. P.; Vijverberg, M. A.; de Jong, T. P.; van Gool, J. D.

    1995-01-01

    To treat enuresis risoria (giggle micturition) by a self-administered electric and imaginary shock and to evaluate the outcome after behavioural therapy. Six boys and three girls with enuresis risoria were evaluated and treated. The mean age at referral was 10.4 years (range 5.7-14.2). All children

  11. 40 CFR 147.2551 - State-administered program-Class II wells.

    Science.gov (United States)

    2010-07-01

    ..., “Re: Application for Primacy in the Regulation of Class II Injection Wells,” March 8, 1982; (5) Letter... Class II Injection Wells under Section 1425 of the Safe Drinking Water Act,” November 1981; (2) Letter...) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS...

  12. 40 CFR 147.50 - State-administered program-Class II wells.

    Science.gov (United States)

    2010-07-01

    ... Carry Out Underground Injection Control Program Relating to Class II Wells as Described in Federal Safe... PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION CONTROL PROGRAMS Alabama... application: (a) Incorporation by reference. The requirements set forth in the State statutes and regulations...

  13. Comparison of the PTSD Checklist (PCL) Administered via a Mobile Device Relative to a Paper Form.

    Science.gov (United States)

    Price, Matthew; Kuhn, Eric; Hoffman, Julia E; Ruzek, Josef; Acierno, Ron

    2015-10-01

    Mobile devices are increasingly used to administer self-report measures of mental health symptoms. There are significant differences, however, in the way that information is presented on mobile devices compared to the traditional paper forms that were used to administer such measures. Such differences may systematically alter responses. The present study evaluated if and how responses differed for a self-report measure, the PTSD Checklist (PCL), administered via mobile device relative to paper and pencil. Participants were 153 trauma-exposed individuals who completed counterbalanced administrations of the PCL on a mobile device and on paper. PCL total scores (d = 0.07) and item responses did not meaningfully or significantly differ across administrations. Power was sufficient to detect a difference in total score between administrations determined by prior work of 3.46 with a d = 0.23. The magnitude of differences between administration formats was unrelated to prior use of mobile devices or participant age. These findings suggest that responses to self-report measures administered via mobile device are equivalent to those obtained via paper and they can be used with experienced as well as naïve users of mobile devices. Copyright © 2015 Wiley Periodicals, Inc., A Wiley Company.

  14. Development and validation of the self-administered Food Allergy Quality of Life Questionnaire for adolescents

    NARCIS (Netherlands)

    Flokstra-de Blok, Bertine M J; DunnGalvin, Audrey; Vlieg-Boerstra, Berber J; Oude Elberink, Joanne N G; Duiverman, Eric J; Hourihane, Jonathan O'Brien; Dubois, Anthony E J

    Background: Food allergy can affect health-related quality of life (HRQL). Currently, no validated, self-administered, disease-specific HRQL questionnaire for adolescents with food allergy exists. Objective: We sought to develop and validate the Food Allergy Quality of Life Questionnaire-Teenager

  15. Effects of Information Feedback and Self-Administered Consequences on Self-Monitoring Study Behavior

    Science.gov (United States)

    Richards, C. Steven; And Others

    1976-01-01

    The hypotheses tested among college students (N=87) concerned about study habits were: (a) self-monitoring changes study behavior; (b) information feedback accounts for some of this change; and (c) this change can be enhanced by manipulating the quantity and quality of information feedback and self-administered consequences associated with…

  16. 40 CFR 147.52 - State-administered program-Hydraulic Fracturing of Coal Beds.

    Science.gov (United States)

    2010-07-01

    ... Fracturing of Coal Beds. 147.52 Section 147.52 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... PROGRAMS Alabama § 147.52 State-administered program—Hydraulic Fracturing of Coal Beds. The UIC program for hydraulic fracturing of coal beds in the State of Alabama, except those on Indian lands, is the program...

  17. Effect of orally administered betel leaf (Piper betle Linn.) on digestive enzymes of pancreas and intestinal mucosa and on bile production in rats.

    Science.gov (United States)

    Prabhu, M S; Platel, K; Saraswathi, G; Srinivasan, K

    1995-10-01

    The influence of two varieties of betel leaf (Piper betle Linn.) namely, the pungent Mysore and non-pungent Ambadi, was examined on digestive enzymes of pancreas and intestinal mucosa and on bile secretion in experimental rats. The betel leaves were administered orally at two doses which were either comparable to human consumption level or 5 times this. The results indicated that while these betel leaves do not influence bile secretion and composition, they have a significant stimulatory influence on pancreatic lipase activity. Besides, the Ambadi variety of betel leaf has a positive stimulatory influence on intestinal digestive enzymes, especially lipase, amylase and disaccharidases. A slight lowering in the activity of these intestinal enzymes was seen when Mysore variety of betel leaf was administered, and this variety also had a negative effect on pancreatic amylase. Further, both the betel leaf varieties have shown decreasing influence on pancreatic trypsin and chymotrypsin activities.

  18. Feasibility of online self-administered cognitive training in moderate-severe brain injury.

    Science.gov (United States)

    Sharma, Bhanu; Tomaszczyk, Jennifer C; Dawson, Deirdre; Turner, Gary R; Colella, Brenda; Green, Robin E A

    2017-07-01

    Cognitive environmental enrichment (C-EE) offers promise for offsetting neural decline that is observed in chronic moderate-severe traumatic brain injury (TBI). Brain games are a delivery modality for C-EE that can be self-administered over the Internet without therapist oversight. To date, only one study has examined the feasibility of self-administered brain games in TBI, and the study focused predominantly on mild TBI. Therefore, the primary purpose of the current study was to examine the feasibility of self-administered brain games in moderate-severe TBI. A secondary and related purpose was to examine the feasibility of remote monitoring of any C-EE-induced adverse symptoms with a self-administered evaluation tool. Ten patients with moderate-severe TBI were asked to complete 12 weeks (60 min/day, five days/week) of online brain games with bi-weekly self-evaluation, intended to measure any adverse consequences of cognitive training (e.g., fatigue, eye strain). There was modest weekly adherence (42.6% ± 4.4%, averaged across patients and weeks) and 70% patient retention; of the seven retained patients, six completed the self-evaluation questionnaire at least once/week for each week of the study. Even patients with moderate-severe TBI can complete a demanding, online C-EE intervention and a self-administered symptom evaluation tool with limited therapist oversight, though at daily rate closer to 30 than 60 min per day. Further self-administered C-EE research is underway in our lab, with more extensive environmental support. Implications for Rehabilitation Online brain games (which may serve as a rehabilitation paradigm that can help offset the neurodegeneration observed in chronic TBI) can be feasibly self-administered by moderate-to-severe TBI patients. Brain games are a promising therapy modality, as they can be accessed by all moderate-to-severe TBI patients irrespective of geographic location, clinic and/or therapist availability, or impairments that

  19. Acute chloroform ingestion successfully treated with intravenously administered N-acetylcysteine.

    Science.gov (United States)

    Dell'Aglio, Damon M; Sutter, Mark E; Schwartz, Michael D; Koch, David D; Algren, D A; Morgan, Brent W

    2010-06-01

    Chloroform, a halogenated hydrocarbon, causes central nervous system depression, cardiac arrhythmias, and hepatotoxicity. We describe a case of chloroform ingestion with a confirmatory serum level and resultant hepatotoxicity successfully treated with intravenously administered N-acetylcysteine (NAC). A 19-year-old man attempting suicide ingested approximately 75 mL of chloroform. He was unresponsive and intubated upon arrival. Intravenously administered NAC was started after initial stabilization was complete. His vital signs were normal. Admission laboratory values revealed normal serum electrolytes, AST, ALT, PT, BUN, creatinine, and bilirubin. Serum ethanol level was 15 mg/dL, and aspirin and acetaminophen were undetectable. The patient was extubated but developed liver function abnormalities with a peak AST of 224 IU/L, ALT of 583 IU/L, and bilirubin level reaching 16.3 mg/dL. NAC was continued through hospital day 6. Serum chloroform level obtained on admission was 91 μg/mL. The patient was discharged to psychiatry without known sequelae and normal liver function tests. The average serum chloroform level in fatal cases of inhalational chloroform poisoning was 64 μg/mL, significantly lower than our patient. The toxicity is believed to be similar in both inhalation and ingestion routes of exposure, with mortality predominantly resulting from anoxia secondary to central nervous system depression. Hepatocellular toxicity is thought to result from free radical-induced oxidative damage. Previous reports describe survival after treatment with orally administered NAC, we report the first use of intravenously administered NAC for chloroform ingestion. Acute oral ingestion of chloroform is extremely rare. Our case illustrates that with appropriate supportive care, patients can recover from chloroform ingestion, and intravenously administered NAC may be of benefit in such cases.

  20. A Retrospective Analysis of Clinical Laboratory Interferences Caused by Frequently Administered Medications in Burn Patients.

    Science.gov (United States)

    Godwin, Zachary; Lima, Kelly; Greenhalgh, David; Palmieri, Tina; Sen, Soman; Tran, Nam K

    2016-01-01

    The goal of this study is to quantify the number of medications administered to burn patients and identify potential drugs interfering with laboratory testing. The authors reviewed the medical records of 12 adult (age ≥ 18 years) burn patients with more than 20% TBSA burns from an existing glucose control database at our institution. Dose, interval, and route of medications administered from admission to discontinuation of intensive insulin therapy were recorded. Interfering drugs were identified based on established clinical chemistry literature. The retrospective cohort of adult burn patients exhibited a mean (SD) age of 37.9 (3.0) years. Mean TBSA burn was 51.3 (9.3)%. Disease severity determined by the average multiple organ dysfunction score was 5.4 (0.2). Mean and median medications administered per day were 42.1 (9.5) and 49 (with a daily range of 0-65), respectively. A total of 666 potential laboratory test interferences caused by medications were identified. There were 261 different effects (eg, increased glucose, decreased potassium). Multiple interferences, 71.0% (475/666), were caused by more than one medication. Investigation of the number of medications administered to a burn patient and delineation of potential laboratory test interferences has not been conducted in burn patients. Given the substantial number of medications administered to burn patients, physicians and laboratory personnel should work together to identify potential interferences and define appropriate countermeasures while enhancing the laboratorians understanding of this unique population. This synergistic partnership can lead to intelligent support tools and potentially autocorrecting instruments.

  1. Nonclinical Safety Assessment of SYN-004: An Oral β-lactamase for the Protection of the Gut Microbiome From Disruption by Biliary-Excreted, Intravenously Administered Antibiotics.

    Science.gov (United States)

    Kokai-Kun, John F; Bristol, J Andrew; Setser, John; Schlosser, Michael

    2016-05-01

    SYN-004 is a first in class, recombinant β-lactamase that degrades β-lactam antibiotics and has been formulated to be administered orally to patients receiving intravenous β-lactam antibiotics including cephalosporins. SYN-004 is intended to degrade unmetabolized antibiotics excreted into the intestines and thus has the potential to protect the gut microbiome from disruption by these antibiotics. Protection of the gut microbiome is expected to protect against opportunistic enteric infections such as Clostridium difficile infection as well as antibiotic-associated diarrhea. In order to demonstrate that oral SYN-004 is safe for human clinical trials, 2 Good Laboratory Practice-compliant toxicity studies were conducted in Beagle dogs. In both studies, SYN-004 was administered orally 3 times per day up to the maximum tolerated dose of the formulation. In the first study, doses of SYN-004 administered over 28 days were safe and well tolerated in dogs with the no-observed-adverse-effect level at the high dose of 57 mg/kg/day. Systemic absorption of SYN-004 was minimal and sporadic and showed no accumulation during the study. In the second study, doses up to 57 mg/kg/day were administered to dogs in combination with an intravenous dose of ceftriaxone (300 mg/kg) given once per day for 14 days. Coadministration of oral SYN-004 with intravenous ceftriaxone was safe and well tolerated, with SYN-004 having no noticeable effect on the plasma pharmacokinetics of ceftriaxone. These preclinical studies demonstrate that SYN-004 is well tolerated and, when coadministered with ceftriaxone, does not interfere with its systemic pharmacokinetics. These data supported advancing SYN-004 into human clinical trials. © The Author(s) 2015.

  2. Safety of administering the canine melanoma DNA vaccine (Oncept) to cats with malignant melanoma - a retrospective study.

    Science.gov (United States)

    Sarbu, Luminita; Kitchell, Barbara E; Bergman, Philip J

    2017-02-01

    Objectives A xenogeneic human tyrosinase DNA vaccine was developed for treatment of dogs with oral malignant melanoma (Oncept; Merial). No studies have evaluated the safety or efficacy of this vaccine in cats. The purpose of this study was to evaluate the safety of the canine melanoma vaccine in cats diagnosed with melanoma. Methods Medical records were reviewed from cats diagnosed with malignant melanoma and treated with the canine melanoma DNA vaccine (Oncept). Data regarding signalment, melanoma location, treatments received, vaccine adverse effects and cause of death were collected. Results A total of 114 melanoma vaccines were administered to 24 cats. Seven cats (11.4%) had clinical adverse effects from a total of 13 vaccines classified as grade 1 or 2 based on the Veterinary Cooperative Oncology Group's common terminology criteria for adverse events v1.1. These included pain on vaccine administration, brief muscle fasciculation, transient inappetence, depression, nausea and mild increase in pigmentation at the injection site. Nineteen cats were deceased at study close. The most common cause of death was melanoma (14 cats). Hematological and biochemical changes were observed in six cats, five of which had concurrent disease or treatments that likely caused or greatly contributed to the laboratory abnormalities found. Therefore, these adverse events were considered unlikely to be caused by the melanoma vaccine. One cat had transient grade 1 hypoalbuminemia, which was possibly caused by the vaccination but not thoroughly evaluated. Conclusions and relevance The canine melanoma DNA vaccine can be safely administered to cats, with minimal risk of adverse effects.

  3. A feasibility study of a new method for electrically producing seizures in man: focal electrically administered seizure therapy [FEAST].

    Science.gov (United States)

    Nahas, Ziad; Short, Baron; Burns, Carol; Archer, Melanie; Schmidt, Matthew; Prudic, Joan; Nobler, Mitchell S; Devanand, D P; Fitzsimons, Linda; Lisanby, Sarah H; Payne, Nancy; Perera, Tarique; George, Mark S; Sackeim, Harold A

    2013-05-01

    Electroconvulsive therapy (ECT) remains the most effective acute treatment for severe major depression, but with significant risk of adverse cognitive effects. Unidirectional electrical stimulation with a novel electrode placement and geometry (Focal Electrically Administered Seizure Therapy (FEAST)) has been proposed as a means to initiate seizures in prefrontal cortex prior to secondary generalization. As such, it may have fewer cognitive side effects than traditional ECT. We report on its first human clinical application. Seventeen unmedicated depressed adults (5 men; 3 bipolar disorder; age 53 ± 16 years) were recruited after being referred for ECT. Open-label FEAST was administered with a modified spECTrum 5000Q device and a traditional ECT dosing regimen until patients clinically responded. Clinical and cognitive assessments were obtained at baseline, and end of course. Time to orientation recovery, a predictor of long-term amnestic effects, was assessed at each treatment. Nonresponders to FEAST were transitioned to conventional ECT. One patient withdrew from the study after a single titration session. After the course of FEAST (median 10 sessions), there was a 46.1 ± 35.5% improvement in Hamilton Rating Scale for Depression (HRSD24) scores compared to baseline (33.1 ± 6.8, 16.8 ± 10.9; P FEAST produced clinically meaningful antidepressant improvement, with relatively short time to reorientation. Our preliminary work first in primates and now depressed adults demonstrates that FEAST is feasible, safe, well-tolerated and, if efficacy can be optimized, has potential to replace traditional ECT. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Challenges in converting an interviewer-administered food probe database to self-administration in the National Cancer Institute Automated Self-administered 24-Hour Recall (ASA24).

    Science.gov (United States)

    Zimmerman, Thea Palmer; Hull, Stephen G; McNutt, Suzanne; Mittl, Beth; Islam, Noemi; Guenther, Patricia M; Thompson, Frances E; Potischman, Nancy A; Subar, Amy F

    2009-12-01

    The National Cancer Institute (NCI) is developing an automated, self-administered 24-hour dietary recall (ASA24) application to collect and code dietary intake data. The goal of the ASA24 development is to create a web-based dietary interview based on the US Department of Agriculture (USDA) Automated Multiple Pass Method (AMPM) instrument currently used in the National Health and Nutrition Examination Survey (NHANES). The ASA24 food list, detail probes, and portion probes were drawn from the AMPM instrument; portion-size pictures from Baylor College of Medicine's Food Intake Recording Software System (FIRSSt) were added; and the food code/portion code assignments were linked to the USDA Food and Nutrient Database for Dietary Studies (FNDDS). The requirements that the interview be self-administered and fully auto-coded presented several challenges as the AMPM probes and responses were linked with the FNDDS food codes and portion pictures. This linking was accomplished through a "food pathway," or the sequence of steps that leads from a respondent's initial food selection, through the AMPM probes and portion pictures, to the point at which a food code and gram weight portion size are assigned. The ASA24 interview database that accomplishes this contains more than 1,100 food probes and more than 2 million food pathways and will include about 10,000 pictures of individual foods depicting up to 8 portion sizes per food. The ASA24 will make the administration of multiple days of recalls in large-scale studies economical and feasible.

  5. Differential effects of systemically administered ketamine and lidocaine on dynamic and static hyperalgesia induced by intradermal capsaicin in humans

    DEFF Research Database (Denmark)

    Gottrup, Hanne; Hansen, Peter Orm; Arendt-Nielsen, Lars

    2000-01-01

    We have examined the effect of systemic administration of ketamine and lidocaine on brush-evoked (dynamic) pain and punctate-evoked (static) hyperalgesia induced by capsaicin. In a randomized, double-blind, placebo-controlled, crossover study, we studied 12 volunteers in three experiments....... Capsaicin 100 micrograms was injected intradermally on the volar forearm followed by an i.v. infusion of ketamine (bolus 0.1 mg kg-1 over 10 min followed by infusion of 7 micrograms kg-1 min-1), lidocaine 5 mg kg-1 or saline for 50 min. Infusion started 15 min after injection of capsaicin. The following...... were measured: spontaneous pain, pain evoked by punctate and brush stimuli (VAS), and areas of brush-evoked and punctate-evoked hyperalgesia. Ketamine reduced both the area of brush-evoked and punctate-evoked hyperalgesia significantly and it tended to reduce brush-evoked pain. Lidocaine reduced...

  6. Lack of immunogenicity of ice structuring protein type III HPLC12 preparation administered by the oral route to human volunteers

    DEFF Research Database (Denmark)

    Crevel, R W R; Cooper, K J; Poulsen, Lars K.

    2007-01-01

    Before a novel protein can be used in foods, its potential allergenicity must be assessed. In this study, healthy volunteers consumed ice structuring protein (ISP) Type III preparation or a control material 5 days a week for a total of 8 weeks. General measures of health were recorded during...... background against which to interpret the results. Nevertheless, the absence of an immune response using a protocol which could have been expected to result in a response with a strongly immunogenic protein, confirms the conclusions of earlier published work, and attests to the lack of allergenicity of ISP...

  7. Psychiatric side effects of ketamine in hospitalized medical patients administered subanesthetic doses for pain control.

    Science.gov (United States)

    Rasmussen, Keith G

    2014-08-01

    To assess the psychiatric side effects of ketamine when administered in subanesthetic doses to hospitalized patients. It is hypothesized that such effects occur frequently. In this retrospective study, the medical records of 50 patients hospitalized on medical and surgical units at our facility who had continuous intravenous infusions of ketamine for pain or mild sedation were reviewed. Patient progress in the days following the start of ketamine infusion was reviewed and response to ketamine was noted. Twenty-two percent of the patients were noted to have some type of psychiatric reaction to ketamine, including agitation, confusion, and hallucinations. These reactions were relatively short lived, namely, occurring during or shortly after the infusions. No association was found between patient response to ketamine and gender, age, or infusion rate. Awareness of the psychiatric side effects of ketamine is an important consideration for clinicians administering this medication either for pain control or for depressive illness.

  8. Safety and efficiency of prehospital pain management with fentanyl administered by emergency medical technicians

    DEFF Research Database (Denmark)

    Nielsen, Niels Dalsgaard; Brogaard, Kjeld; Dahl, Michael

    2007-01-01

    Introduction: In our region Advanced Emergency Medical Technicians (AEMTs) respond to acutely ill or injured patients in rural areas. The AEMTs have been authorized to administer fentanyl intravenously in doses up to 2 μg/kg to selected groups of patients in pain. Higher doses can be allowed...... by a physician after a teleconference. We examined the effect of intravenous (IV) fentanyl treatment, expressed as pain reduction on a 10-point Numeric Rating Scale (NRS). Moreover we examined the occurrence of negative coincident events to assess whether it was safe to let non-medical staff administer potent...... opioids intravenously.   Methods: Retrospectively we collected the case sheets for all patients treated with IV fentanyl by the AEMTs in 2005 and 2006. We excluded all patients where a physician had been directly involved in the prehospital treatment. We recorded the IV fentanyl dose, NRS-score before...

  9. Optimization of administered radionuclide activity in renal studies using 99mTc -DMSA in Cuba

    International Nuclear Information System (INIS)

    Diaz Barreto, M.; Perez Diaz, M.; Lopez Bejerano, G. M.; Varela Corona, C.; Paz Viera, J. E.

    2009-01-01

    The present research is focused on the optimization of administered radionuclide activity in renal studies using 9 9mTc-DMSA. The patients sample included 35 subjects, 23 of them were children and the other 12 were adults. Physical and metabolic characteristics of patients, total time of the study as well as radiopharmaceuticals quality and gamma camera performance was considered in the experiments. Image quality of each study was evaluated using subjective criteria from two expert observers, without previous information about administered activity, and objective criteria based on signal/noise ratios and variance of the random noise in the images. They were used to develop clustering and discriminant analysis over the independent variables to detect groups of images with differentiated quality from the physical and mathematical point of view. As a conclusion, we found that it is possible to reduce the given activities in 50%. (Author) 30 refs.

  10. Administered activities of 18F-FDG PET clinics in pediatrics patients in Brazil- preliminary study

    International Nuclear Information System (INIS)

    Oliveira, Cassio Miri; Sa, Lidia V. de

    2013-01-01

    A survey was conducted among the Brazilian clinical PET, with the purpose of investigating the activities administered to pediatric oncology patients and assess whether significant differences between the protocols adopted. In addition, this survey can cooperate to the suggestion diagnostic reference levels (DRLs) in nuclear medicine. Although the methodology for delivering doses by most clinics be based on patient's weight, the results showed variations of up to 191, 6% between the activities administered in clinics, even for similar devices. The average value of the distribution of activities reported was 4.46 ± 1,6 MBq /kg. These data demonstrate the need for harmonization and optimization of 18 F-FDG/PET procedures, as well as training for professionals involved in the clinical routine

  11. Radiosynthesis of 123I-labeled hesperetin for biodistribution study of orally administered hesperetin

    International Nuclear Information System (INIS)

    Jongho Jeon; So-Young Ma; Dae Seong Choi; Beom-Su Jang; Jung Ae Kang; You Ree Nam; Seonhye Yoon; Sang Hyun Park; Korea University of Science and Technology, Daejeon

    2015-01-01

    The purpose of this study is to synthesize 123 I-labeled hesperetin and to investigate its in vivo behavior. The optimized labeling condition provided two isomers of 123 I-labeled hesperetin with high radiochemical yields and radiochemical purities. Both 123 I-labeled products were orally administered to normal ICR mice, and the initial result showed that most of 123 I activity was detected in the stomach and the intestines. A part of 123 I-labeled hesperetin was absorbed from the small intestine to bloodstream and then it was distributed in normal organs. The results in the present study provided an efficient radiolabeling method of flavonoid and quantitative organ distribution of orally administered hesperetin. (author)

  12. Psychology of computer use: IX. A menu of self-administered microcomputer-based neurotoxicology tests

    Science.gov (United States)

    Kennedy, R. S.; Baltzley, D. R.; Wilkes, R. L.; Kuntz, L. A.

    1989-01-01

    This study examined the feasibility of repeated self-administration of a newly developed battery of mental acuity tests which may have application in screening for fitness-for-duty or for persons who may be exposed to environmental stress, toxic agents, or disease. 16 subjects self-administered 18 microcomputer-based tests (13 new, 5 "core"), without proctors, over 10 sessions. The hardware performed well throughout the study and the tests appeared to be easily self-administered. Stabilities and reliabilities of the tests from the "core" battery were comparable to those obtained previously under more controlled experimental conditions. Eight of the new tests exceeded minimum criteria for metric and practical requirements and can be recommended as additions to the menu. Although the average retest reliability was high, cross-correlations between tests were low, implying factorial diversity. The menu can be used to form batteries with flexible total testing time which are likely to tap different mental processes and functions.

  13. Radiation dose calculations for orally administered radio-pharmaceuticals in upper gastrointestinal disease

    International Nuclear Information System (INIS)

    Wu, R.K.; Malmud, L.S.; Knight, L.C.; Siegel, J.A.; Stern, H.; Zelac, R.

    1983-01-01

    Radiation burden estimates for upper gastrointestinal function studies employing the following orally administered radiopharmaceuticals are reported. Technetium 99m sulfur colloid (Tc-99m-SC) in water, Indium-111-DTPA in water, Tc-99m-DTPA in water, Indium-113m DTPA in water, Tc-99m Ovalbumin, Tc-99m sulfur colloid in a cooked egg, Tc-99m sulfur colloid in vivo labeled chicken liver, and Indium-111 colloid in vivo labeled chicken liver. Orally administered radiopharmaceuticals for upper gastrointestinal studies afford clinician and investigator valuable clinical and physiologic information not previously obtainable using other techniques. The radiation burden to the patient from single or sequential studies is acceptable in comparison to fluoroscopy which results in approximately 5000 millirem per minute of exposure. The variety of preparations listed above should make these types of studies available in any routinely equipped nuclear medicine radiopharmacy laboratory

  14. A Pilot Project Demonstrating that Combat Medics Can Safely Administer Parenteral Medications in the Emergency Department.

    Science.gov (United States)

    Schauer, Steven G; Cunningham, Cord W; Fisher, Andrew D; DeLorenzo, Robert A

    2017-12-01

    Introduction Select units in the military have improved combat medic training by integrating their functions into routine clinical care activities with measurable improvements in battlefield care. This level of integration is currently limited to special operations units. It is unknown if regular Army units and combat medics can emulate these successes. The goal of this project was to determine whether US Army combat medics can be integrated into routine emergency department (ED) clinical care, specifically medication administration. Project Design This was a quality assurance project that monitored training of combat medics to administer parenteral medications and to ensure patient safety. Combat medics were provided training that included direct supervision during medication administration. Once proficiency was demonstrated, combat medics would prepare the medications under direct supervision, followed by indirect supervision during administration. As part of the quality assurance and safety processes, combat medics were required to document all medication administrations, supervising provider, and unexpected adverse events. Additional quality assurance follow-up occurred via complete chart review by the project lead. Data During the project period, the combat medics administered the following medications: ketamine (n=13), morphine (n=8), ketorolac (n=7), fentanyl (n=5), ondansetron (n=4), and other (n=6). No adverse events or patient safety events were reported by the combat medics or discovered during the quality assurance process. In this limited case series, combat medics safely administered parenteral medications under indirect provider supervision. Future research is needed to further develop this training model for both the military and civilian setting. Schauer SG , Cunningham C W, Fisher AD , DeLorenzo RA . A pilot project demonstrating that combat medics can safely administer parenteral medications in the emergency department. Prehosp Disaster Med. 2017;32(6):679-681.

  15. Chelation in metal intoxication. VIII. Removal of chromium from organs of potassium chromate administered rats.

    Science.gov (United States)

    Behari, J R; Tandon, S K

    1980-03-01

    Some polyaminocarboxylic acids were examined for their ability to mobilize chromium from certain vital organs, their subcellular fractions, and blood cells of potassium chromate administered rats. Hexamethylene 1,6-diamino tetraacetic acid (TDTA), triethylene tetramine hexaacetic acid (TTHA), and ethylene diamine di (O-hydroxylphenyl acetic acid) (EDDHA) may be useful in preventing or reducing chromate toxicity. No definite relationship could be observed between the structure of the chelating agents and their chromium-removing capacity.

  16. Urinary excretion and external radiation dose from patients administered with radiopharmaceuticals

    International Nuclear Information System (INIS)

    Konishi, E.; Abe, K.; Kusama, T.

    1994-01-01

    Patients who have received radiopharmaceuticals become a source of exposure to those near them, such as nursing staff or visiting relatives. In order to provide quantitative information to propose protective measures for carers attending patients administered diagnostic amounts of 99 Tc, 67 Ga or 201 Tl (the most frequently used radiopharmaceuticals) the dose rate at various distances from 84 patients was measured using an ionising chamber, and the radioactivity of these compounds in urine collected from some patients was also measured. (author)

  17. Subunit Rotavirus Vaccine Administered Parenterally to Rabbits Induces Active Protective Immunity

    Science.gov (United States)

    Ciarlet, Max; Crawford, Sue E.; Barone, Christopher; Bertolotti-Ciarlet, Andrea; Ramig, Robert F.; Estes, Mary K.; Conner, Margaret E.

    1998-01-01

    Virus-like particles (VLPs) are being evaluated as a candidate rotavirus vaccine. The immunogenicity and protective efficacy of different formulations of VLPs administered parenterally to rabbits were tested. Two doses of VLPs (2/6-, G3 2/6/7-, or P[2], G3 2/4/6/7-VLPs) or SA11 simian rotavirus in Freund’s adjuvants, QS-21 (saponin adjuvant), or aluminum phosphate (AlP) were administered. Serological and mucosal immune responses were evaluated in all vaccinated and control rabbits before and after oral challenge with 103 50% infective doses of live P[14], G3 ALA lapine rotavirus. All VLP- and SA11-vaccinated rabbits developed high levels of rotavirus-specific serum and intestinal immunoglobulin G (IgG) antibodies but not intestinal IgA antibodies. SA11 and 2/4/6/7-VLPs afforded similar but much higher mean levels of protection than 2/6/7- or 2/6-VLPs in QS-21. The presence of neutralizing antibodies to VP4 correlated (P < 0.001, r = 0.55; Pearson’s correlation coefficient) with enhanced protection rates, suggesting that these antibodies are important for protection. Although the inclusion of VP4 resulted in higher mean protection levels, high levels of protection (87 to 100%) from infection were observed in individual rabbits immunized with 2/6/7- or 2/6-VLPs in Freund’s adjuvants. Therefore, neither VP7 nor VP4 was absolutely required to achieve protection from infection in the rabbit model when Freund’s adjuvant was used. Our results show that VLPs are immunogenic when administered parenterally to rabbits and that Freund’s adjuvant is a better adjuvant than QS-21. The use of the rabbit model may help further our understanding of the critical rotavirus proteins needed to induce active protection. VLPs are a promising candidate for a parenterally administered subunit rotavirus vaccine. PMID:9765471

  18. Peripherally Administered Nanoparticles Target Monocytic Myeloid Cells, Secondary Lymphoid Organs and Tumors in Mice

    OpenAIRE

    Kourtis, Iraklis C.; Hirosue, Sachiko; de Titta, Alexandre; Kontos, Stephan; Stegmann, Toon; Hubbell, Jeffrey A.; Swartz, Melody A.

    2013-01-01

    Nanoparticles have been extensively developed for therapeutic and diagnostic applications. While the focus of nanoparticle trafficking in vivo has traditionally been on drug delivery and organ-level biodistribution and clearance, recent work in cancer biology and infectious disease suggests that targeting different cells within a given organ can substantially affect the quality of the immunological response. Here, we examine the cell-level biodistribution kinetics after administering ultrasma...

  19. Identification of drug combinations administered by continuous subcutaneous infusion that require analysis for compatibility and stability

    OpenAIRE

    Dickman, Andrew; Bickerstaff, Matthew; Jackson, Richard; Schneider, Jennifer; Mason, Stephen; Ellershaw, John

    2017-01-01

    Background A continuous subcutaneous infusion (CSCI) delivered via syringe pump is a method of drug administration used to maintain symptom control when a patient is no longer able to tolerate oral medication. Several classes of drugs, such as opioids, antiemetics, anticholinergics, antipsychotics and benzodiazepines are routinely administered by CSCI alone or in combinations. Previous studies attempting to identify the most-common CSCI combinations are now several years old and no longer ref...

  20. Self-administered foot reflexology for the management of chronic health conditions: a systematic review.

    Science.gov (United States)

    Song, Hyun Jin; Choi, Sun Mi; Seo, Hyun-Ju; Lee, Heeyoung; Son, Heejeong; Lee, Sanghun

    2015-02-01

    To systematically review the effect of self-administered foot reflexology in patients with chronic health conditions. Electronic databases were searched for literature published from 1948 to January 2014. The databases included MEDLINE, EMBASE, the Cochrane Library, CINAHL, CNKI, J-STAGE, Koreamed, Kmbase, KISS, NDSL, KISTI, and OASIS. Key search terms were "exp/relaxation therapy," "foot," "reflexology," "zone therapy," and "self." All study designs were included. Two raters independently extracted data and assessed study quality by using the Cochrane risk of bias tool (for randomized controlled trials) and the risk of bias assessment tool for nonrandomized studies (for nonrandomized and before-and-after studies). A qualitative and descriptive analysis was performed because of the clinical diversity associated with chronic health conditions. Of the 224 records assessed, 4 trials met the inclusion criteria: 3 nonrandomized controlled trials and 1 before-and-after study without comparison. Self-administered foot reflexology might have a positive effect in type 2 diabetes, but the low quality of the included study and the lack of adequately reported clinical outcomes obscure the results. Two studies of hypertensive patients and 1 study of patients with urinary incontinence showed that self-performed foot reflexology may exert a beneficial effect on lowering blood pressure and urinary incontinence; however, given the small sample size and the lack of any description of medications and other cointerventions, there was insufficient evidence to conclusively determine whether foot reflexology had any effect. The included studies on self-administered foot reflexology in patients with type 2 diabetes, hypertension, or urinary incontinence provided insufficient evidence to determine a treatment effect. Therefore, a well-designed, large-scale, and randomized controlled trial is needed to confirm the effect of self-administered foot reflexology for chronic conditions.

  1. Development of a self-administered questionnaire to screen patients for cervical myelopathy

    Directory of Open Access Journals (Sweden)

    Sekiguchi Yasufumi

    2010-11-01

    Full Text Available Abstract Background In primary care, it is often difficult to diagnose cervical myelopathy. However, a delay in treatment could cause irreversible aftereffects. With a brief and effective self-administered questionnaire for cervical myelopathy, cervical myelopathy may be screened more easily and oversight may be avoided. As there is presently no screening tool for cervical myelopathy, the aim of this study was to develop a self-administered questionnaire for the screening of cervical myelopathy. Methods A case-control study was performed with the following two groups at our university hospital from February 2006 to September 2008. Sixty-two patients (48 men, 14 women with cervical myelopathy who underwent operative treatment were included in the myelopathy group. In the control group, 49 patients (20 men, 29 women with symptoms that could be distinguished from those of cervical myelopathy, such as numbness, pain in the upper extremities, and manual clumsiness, were included. The underlying conditions were diagnosed as carpal tunnel syndrome, cubital tunnel syndrome, thoracic outlet syndrome, tarsal tunnel syndrome, diabetes mellitus neuropathy, cervical radiculopathy, and neuralgic amyotrophy. Twenty items for a questionnaire in this study were chosen from the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire, which is a new self-administered questionnaire, as an outcome measure for patients with cervical myelopathy. Data were analyzed by univariate analysis using the chi-square test and by multiple logistic regression analysis. According to the resulting odds ratio, β-coefficients, and p value, items were chosen and assigned a score. Results Eight items were chosen by univariate and multiple logistic regression analyses and assigned a score. The Hosmer-Lemeshow statistic showed p = 0.805. The area under the receiver operation characteristic curve was 0.86. The developed questionnaire had a sensitivity of 93.5% and a

  2. Pharmacokinetics of a new subcutaneous diclofenac formulation administered to three body sites: quadriceps, gluteus, and abdomen.

    Science.gov (United States)

    Salomone, Salvatore; Piazza, Cateno; Vitale, Daniela Cristina; Cardì, Francesco; Gugliotta, Barbara; Drago, Filippo

    2014-02-01

    To assess the relative bioavailability of a new subcutaneous (SC) diclofenac hydroxypropyl b-cyclodextrin (HPbCD) formulation administered to three body sites: quadriceps, gluteus, and abdomen. This was a pilot, single-dose, randomized, three-way crossover relative bioavailability study. A total of 12 healthy subjects received a single SC injection of diclofenac HPbCD 50 mg/1 mL in the quadriceps, gluteus, or abdomen. The AUC was comparable after SC diclofenac HPbCD in the quadriceps, gluteus, and abdomen. The Cmax was comparable after SC administration in the quadriceps or abdomen, and ~ 17% higher in the gluteus. The absorption was rapid (30 minutes) after administration of the treatment at any site. The treatment was well tolerated. The relative bioavailability of SC diclofenac HPbCD was comparable when administered to the quadriceps, gluteus, and abdomen. The new diclofenac formulation can therefore be administered subcutaneously to any of these sites without clinically significant differences. A further adequately powered study would be necessary to reveal any differences among injection sites in terms of peak plasma concentration.

  3. Pharmacodynamics of oxytetracycline administered alone and in combination with carprofen in calves.

    Science.gov (United States)

    Brentnall, C; Cheng, Z; McKellar, Q A; Lees, P

    2012-09-15

    The pharmacodynamics (PD) of oxytetracycline was investigated against a strain of Mannheimia haemolytica. In vitro measurements, comprising minimum inhibitory concentration (MIC), minimum bactericidal concentration and time-kill curves, were conducted in five matrices; Mueller Hinton Broth (MHB), cation-adjusted MHB (CAMHB) and calf serum, exudate and transudate. MICs were much higher in the biological fluids than in MHB and CAMHB. Ratios of MIC were, serum: CAMHB 19 : 1; exudate:CAMHB 16.1; transudate:CAMHB 14 : 1. Ex vivo data, generated in the tissue cage model of inflammation, demonstrated that oxytetracycline, administered to calves intramuscularly at a dose rate of 20 mg/kg, did not inhibit the growth of M haemolytica in serum, exudate and transudate, even at peak concentration. However, using in vitro susceptibility in CAMHB and in vivo-determined pharmacokinetic (PK) variables, average and minimum oxytetracycline concentrations relative to MIC (C(av)/MIC and C(min)/MIC) predicted achievement of efficacy for approximately 48 hours after dosing. Similar C(av)/MIC and C(min)/MIC data were obtained when oxytetracycline was administered in the presence of carprofen. PK-PD integration of data for oxytetracycline, based on MICs determined in the three biological fluids, suggests that it possesses, at most, limited direct killing activity against M haemolytica. These data raise questions concerning the mechanism(s) of action of oxytetracycline, when administered at clinically recommended dose rates.

  4. Milrinone and levosimendan administered after reperfusion improve myocardial stunning in swine.

    Science.gov (United States)

    Shibata, Itsuko; Cho, Sungsam; Yoshitomi, Osamu; Ureshino, Hiroyuki; Maekawa, Takuji; Hara, Tetsuya; Sumikawa, Koji

    2013-02-01

    We assessed the effect of milrinone application timing after reperfusion against myocardial stunning as compared with levosimendan in swine. Furthermore, we examined the role of p38 mitogen-activated protein kinase (p38 MAPK) in the milrinone-induced cardioprotection. All swine were subjected to 12-minutes ischemia followed by 90-minutes reperfusion to generate stunned myocardium. Milrinone or levosimendan was administered intravenously either for 20 minutes starting just after reperfusion or for 70 minutes starting 20 minutes after reperfusion. In another group, SB203580, a selective p38 MAPK inhibitor, was administered with and without milrinone. Regional myocardial contractility was assessed by percent segment shortening (%SS). Milrinone starting just after reperfusion, but not starting 20 minutes after reperfusion, improved %SS at 30, 60, and 90 minutes after reperfusion compared with that in the control group. SB203580 abolished the beneficial effect of milrinone. On the other hand, levosimendan starting 20 minutes after reperfusion, but not for 20 minutes starting just after reperfusion, improved %SS at 60 and 90 minutes after reperfusion. Milrinone should be administered just after reperfusion to protect myocardial stunning through p38 MAPK, whereas levosimendan improvement of contractile function could be mainly dependent on its positive inotropic effect.

  5. Recommended administered activities for {sup 68}Ga-labelled peptides in paediatric nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    Machado, J.S.; Beykan, S.; Lassmann, M. [University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Herrmann, K. [University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States)

    2016-10-15

    The aim of this study was to establish a method for determining administered activities for {sup 68}Ga-labelled peptides. Dose calculations were based on the weight-independent effective dose model proposed by the EANM paediatric dosage card for use in paediatric nuclear medicine. Previously published time-integrated activity coefficients for {sup 68}Ga-DOTATATE, {sup 68}Ga-DOTATOC and {sup 68}Ga-pentixafor were used to calculate age-independent effective doses. Consequently, the corresponding weight-dependent effective dose coefficients were rescaled according to the formalism of the EANM dosage card to determine the radiopharmaceutical class of {sup 68}Ga-labelled peptides (''multiples'') and to calculate the baseline activities based on an upper limit for administered activity (185 MBq) in an adult. All calculated normalization factors suggest that the {sup 68}Ga-labelled peptides are class ''B'' radiopharmaceuticals. The baseline activity for all compounds is 12.8 MBq. In analogy to {sup 18}F-fluoride, we recommend a minimum activity of 14 MBq. For paediatric nuclear medicine applications involving {sup 68}Ga-labelled peptides, we suggest determining administered activities based on the formalism proposed in this work. The corresponding effective doses from these procedures will remain age-independent. (orig.)

  6. Sodium Nitrite and Sodium Thiosulfate Are Effective Against Acute Cyanide Poisoning When Administered by Intramuscular Injection.

    Science.gov (United States)

    Bebarta, Vikhyat S; Brittain, Matthew; Chan, Adriano; Garrett, Norma; Yoon, David; Burney, Tanya; Mukai, David; Babin, Michael; Pilz, Renate B; Mahon, Sari B; Brenner, Matthew; Boss, Gerry R

    2017-06-01

    The 2 antidotes for acute cyanide poisoning in the United States must be administered by intravenous injection. In the out-of-hospital setting, intravenous injection is not practical, particularly for mass casualties, and intramuscular injection would be preferred. The purpose of this study is to determine whether sodium nitrite and sodium thiosulfate are effective cyanide antidotes when administered by intramuscular injection. We used a randomized, nonblinded, parallel-group study design in 3 mammalian models: cyanide gas inhalation in mice, with treatment postexposure; intravenous sodium cyanide infusion in rabbits, with severe hypotension as the trigger for treatment; and intravenous potassium cyanide infusion in pigs, with apnea as the trigger for treatment. The drugs were administered by intramuscular injection, and all 3 models were lethal in the absence of therapy. We found that sodium nitrite and sodium thiosulfate individually rescued 100% of the mice, and that the combination of the 2 drugs rescued 73% of the rabbits and 80% of the pigs. In all 3 species, survival in treated animals was significantly better than in control animals (log rank test, Pcyanide poisoning in 3 clinically relevant animal models of out-of-hospital emergency care. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  7. Nurse-Administered, Gut-Directed Hypnotherapy in IBS: Efficacy and Factors Predicting a Positive Response.

    Science.gov (United States)

    Lövdahl, Jenny; Ringström, Gisela; Agerforz, Pia; Törnblom, Hans; Simrén, Magnus

    2015-07-01

    Hypnotherapy is an effective treatment in irritable bowel syndrome (IBS). It is often delivered by a psychotherapist and is costly and time consuming. Nurse-administered hypnotherapy could increase availability and reduce costs. In this study the authors evaluate the effectiveness of nurse-administered, gut-directed hypnotherapy and identify factors predicting treatment outcome. Eighty-five patients were included in the study. Participants received hypnotherapy by a nurse once/week for 12 weeks. Patients reported marked improvement in gastrointestinal (GI) and extra-colonic symptoms after treatment, as well as a reduction in GI-specific anxiety, general anxiety, and depression. Fifty-eight percent were responders after the 12 weeks treatment period, and of these 82% had a favorable clinical response already at week 6. Women were more likely than men to respond favorably to the treatment. Nurse-administered hypnotherapy is an effective treatment for IBS. Being female and reporting a favorable response to treatment by week 6 predicted a positive treatment response at the end of the 12 weeks treatment period.

  8. Pair housing differentially affects motivation to self-administer cocaine in male and female rats.

    Science.gov (United States)

    Westenbroek, Christel; Perry, Adam N; Becker, Jill B

    2013-09-01

    Female rats exhibit greater intake and motivation to self-administer cocaine. In females but not males, isolation by itself is a stressor, which could lead to increased drug intake. Therefore, we hypothesized that social housing would buffer against stress and reduce the motivation to self-administer cocaine primarily in females. Male and female Sprague-Dawley rats were housed individually or in same-sex pairs. The individually housed rats and one of each pair were allowed to self-administer (SA) a low dose of cocaine (0.2 mg/kg/inf) on a fixed ratio (FR1) schedule for one week. Motivation for cocaine SA was measured for an additional 2 weeks on a progressive ratio schedule. Isolated females had greater cocaine-intake on the FR1 schedule and greater motivation to take cocaine than males. Pair-housing in females, but not males, attenuated the motivation to take cocaine. Isolated females, but not males, showed escalation of their motivation to take cocaine, which was attenuated by pair housing of females. Concluding, the motivation to take cocaine escalates in females but not males, and pair-housing of females attenuates this escalation. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Pharmacists as immunizers: a survey of community pharmacists' willingness to administer adult immunizations.

    Science.gov (United States)

    Edwards, Nicholas; Gorman Corsten, Erin; Kiberd, Mathew; Bowles, Susan; Isenor, Jennifer; Slayter, Kathryn; McNeil, Shelly

    2015-04-01

    Adult immunization rates worldwide fall below desired targets. Pharmacists are highly accessible healthcare providers with the potential to increase immunization rates among adults by administering vaccines in their practice setting. To determine the attitudes of community-based Canadian pharmacists with respect to expanding their scope of practice to include administration of immunizations. An internet-based survey was emailed to community pharmacists across Canada. The survey was piloted through focus groups for qualitative feedback, tested for content validity, and test-retest reliability prior to dissemination. There were 495 responses to the survey. The majority (88 %) agreed that pharmacists as immunizers would increase public access, improve rates (84 %), and be acceptable to the public (72 %). However, only 68 % agreed that pharmacists should be permitted to immunize. The majority of respondents (90 %) agreed that certification in vaccine administration should be required for pharmacists to administer vaccines. Pharmacists identified education, reimbursement, and negative interactions with other providers as barriers to pharmacists administering vaccines. Canadian pharmacists are willing to expand their scope of practice to include immunization. However, implementation requires professional development and certification in vaccine administration.

  10. 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.

    1982-01-01

    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%

  11. Distinct Neurochemical Adaptations Within the Nucleus Accumbens Produced by a History of Self-Administered vs Non-Contingently Administered Intravenous Methamphetamine

    Science.gov (United States)

    Lominac, Kevin D; Sacramento, Arianne D; Szumlinski, Karen K; Kippin, Tod E

    2012-01-01

    Methamphetamine is a highly addictive psychomotor stimulant yet the neurobiological consequences of methamphetamine self-administration remain under-characterized. Thus, we employed microdialysis in rats trained to self-administer intravenous (IV) infusions of methamphetamine (METH-SA) or saline (SAL) and a group of rats receiving non-contingent IV infusions of methamphetamine (METH-NC) at 1 or 21 days withdrawal to determine the dopamine and glutamate responses in the nucleus accumbens (NAC) to a 2 mg/kg methamphetamine intraperitoneal challenge. Furthermore, basal NAC extracellular glutamate content was assessed employing no net-flux procedures in these three groups at both time points. At both 1- and 21-day withdrawal points, methamphetamine elicited a rise in extracellular dopamine in SAL animals and this effect was sensitized in METH-NC rats. However, METH-SA animals showed a much greater sensitized dopamine response to the drug challenge compared with the other groups. Additionally, acute methamphetamine decreased extracellular glutamate in both SAL and METH-NC animals at both time-points. In contrast, METH-SA rats exhibited a modest and delayed rise in glutamate at 1-day withdrawal and this rise was sensitized at 21 days withdrawal. Finally, no net-flux microdialysis revealed elevated basal glutamate and increased extraction fraction at both withdrawal time-points in METH-SA rats. Although METH-NC rats exhibited no change in the glutamate extraction fraction, they exhibited a time-dependent elevation in basal glutamate levels. These data illustrate for the first time that a history of methamphetamine self-administration produces enduring changes in NAC neurotransmission and that non-pharmacological factors have a critical role in the expression of these methamphetamine-induced neurochemical adaptations. PMID:22030712

  12. Comparison of morphine and carprofen administered alone or in combination for analgesia in dogs undergoing ovariohysterectomy

    Directory of Open Access Journals (Sweden)

    T.B. Dzikiti

    2006-06-01

    Full Text Available In this study the analgesic efficacy of the pure agonistic opioid morphine and the cyclo-oxygenase type-2-selective carprofen were compared since there is no previous specific comparative study for these two common analgesics. Forty-five bitches undergoing elective ovariohysterectomy were randomly assigned to one of three groups; receiving morphine 0.4 mg/kg bodyweight pre-operatively and 0.2 mg/kg every 4-6 hours thereafter (Morphine group, receiving a once-off carprofen 4 mg/kg injection (Carprofen group or receiving both morphine and carprofen (MorphCarp group. The dogs were premedicated with acepromazine 0.01 mg/kg and induced with either thiopentone 5-10 mg/kg or propofol 4-6 mg/kg. General anaesthesia was maintained with halothane in oxygen. The degree of pain was assessed over a 24-hour period under blinded conditions using a pain scale modified from the University of Melbourne pain scale and the Glasgow composite pain tool. Physiological parameters such as respiratory rate, pulse rate and body temperature were also assessed over the same time period. There was no significant difference in pain-scores and thus analgesia offered by the three analgesia protocols at any assessment point across the three groups, but there were differences within groups across time points. Baseline total pain-scores were lower than scores at all post-operative points within all three groups. Both morphine and carprofen provided good analgesia without any obvious adverse effects. This study indicates that at the dosages indicated above, carprofen administered on its own produces analgesia equal to that produced by morphine and that the two drugs administered together do not produce better analgesia than either drug administered on its own.

  13. Comparison of morphine and carprofen administered alone or in combination for analgesia in dogs undergoing ovariohysterectomy.

    Science.gov (United States)

    Dzikiti, T B; Joubert, K E; Venter, L J; Dzikiti, L N

    2006-09-01

    In this study the analgesic efficacy of the pure agonistic opioid morphine and the cyclo-oxygenase type-2-selective carprofen were compared since there is no previous specific comparative study for these two common analgesics. Forty-five bitches undergoing elective ovariohysterectomy were randomly assigned to one of three groups; receiving morphine 0.4 mg/kg bodyweight pre-operatively and 0.2 mg/kg every 4-6 hours thereafter (Morphine group), receiving a once-off carprofen 4 mg/kg injection (Carprofen group) or receiving both morphine and carprofen (MorphCarp group). The dogs were premedicated with acepromazine 0.01 mg/kg and induced with either thiopentone 5-10 mg/kg or propofol 4-6 mg/kg. General anaesthesia was maintained with halothane in oxygen. The degree of pain was assessed over a 24-hour period under blinded conditions using a pain scale modified from the University of Melbourne pain scale and the Glasgow composite pain tool. Physiological parameters such as respiratory rate, pulse rate and body temperature were also assessed over the same time period. There was no significant difference in pain-scores and thus analgesia offered by the three analgesia protocols at any assessment point across the three groups, but there were differences within groups across time points. Baseline total pain-scores were lower than scores at all post-operative points within all three groups. Both morphine and carprofen provided good analgesia without any obvious adverse effects. This study indicates that at the dosages indicated above, carprofen administered on its own produces analgesia equal to that produced by morphine and that the two drugs administered together do not produce better analgesia than either drug administered on its own.

  14. Exposure control practices for administering nitrous oxide: A survey of dentists, dental hygienists, and dental assistants.

    Science.gov (United States)

    Boiano, James M; Steege, Andrea L; Sweeney, Marie H

    2017-06-01

    Engineering, administrative, and work practice controls have been recommended for many years to minimize exposure to nitrous oxide during dental procedures. To better understand the extent to which these exposure controls are used, the NIOSH Health and Safety Practices Survey of Healthcare Workers was conducted among members of professional practice organizations representing dentists, dental hygienists and dental assistants. The anonymous, modular, web-based survey was completed by 284 dental professionals in private practice who administered nitrous oxide to adult and/or pediatric patients in the seven days prior to the survey. Use of primary engineering controls (i.e., nasal scavenging mask and/or local exhaust ventilation (LEV) near the patient's mouth) was nearly universal, reported by 93% and 96% of respondents who administered to adult (A) and pediatric (P) patients, respectively. However, adherence to other recommended precautionary practices were lacking to varying degrees, and were essentially no different among those administering nitrous oxide to adult or pediatric patients. Examples of work practices which increase exposure risk, expressed as percent of respondents, included: not checking nitrous oxide equipment for leaks (41% A; 48% P); starting nitrous oxide gas flow before delivery mask or airway mask was applied to patient (13% A; 12% P); and not turning off nitrous oxide gas flow before turning off oxygen flow to the patient (8% A; 7% P). Absence of standard procedures to minimize worker exposure to nitrous oxide (13% of all respondents) and not being trained on safe handling and administration of nitrous oxide (3%) were examples of breaches of administrative controls which may also increase exposure risk. Successful management of nitrous oxide emissions should include properly fitted nasal scavenging masks, supplemental LEV (when nitrous oxide levels cannot be adequately controlled using nasal masks alone), adequate general ventilation, regular

  15. Interviewer versus self-administered health-related quality of life questionnaires - Does it matter?

    Directory of Open Access Journals (Sweden)

    Ackatz Lori E

    2011-05-01

    Full Text Available Abstract Background Patient-reported outcomes are measured in many epidemiologic studies using self- or interviewer-administered questionnaires. While in some studies differences between these administration formats were observed, other studies did not show statistically significant differences important to patients. Since the evidence about the effect of administration format is inconsistent and mainly available from cross-sectional studies our aim was to assess the effects of different administration formats on repeated measurements of patient-reported outcomes in participants with AIDS enrolled in the Longitudinal Study of Ocular Complications of AIDS. Methods We included participants enrolled in the Longitudinal Study of Ocular Complications in AIDS (LSOCA who completed the Medical Outcome Study [MOS] -HIV questionnaire, the EuroQol, the Feeling Thermometer and the Visual Function Questionnaire (VFQ 25 every six months thereafter using self- or interviewer-administration. A large print questionnaire was available for participants with visual impairment. Considering all measurements over time and adjusting for patient and study site characteristics we used linear models to compare HRQL scores (all scores from 0-100 between administration formats. We defined adjusted differences of ≥0.2 standard deviations [SD] to be quantitatively meaningful. Results We included 2,261 participants (80.6% males with a median of 43.1 years of age at enrolment who provided data on 23,420 study visits. The self-administered MOS-HIV, Feeling Thermometer and EuroQol were used in 70% of all visits and the VFQ-25 in 80%. For eight domains of the MOS-HIV differences between the interviewer- and self- administered format were Conclusions Our large study provides evidence that administration formats do not have a meaningful effect on repeated measurements of patient-reported outcomes. As a consequence, longitudinal studies may not need to consider the effect of

  16. Doses of radioiodine administered for hyperthyroidism: a sampling of Belgian nuclear medicine physician's attitudes

    International Nuclear Information System (INIS)

    Tondeur Dejonckheere, Marianne; Glinoer, Daniel; Verelst, Jean; Sand, Alain; Ham, Hamphrey

    2005-01-01

    Full text: While radioiodine (RI) is a well established treatment for hyperthyroidism, there is no consensus regarding the administration of fixed or calculated doses. Guidelines from scientific societies do not specify the preferable approach, nor the parameters to be used in order to calculate the latter. Therefore, the doses might, for the same patient, be different with regard to the chosen procedure. This study was undertaken to assess the variability of RI amounts administered in Belgium in various cases of hyperthyroidism. 21 Belgian nuclear medicine physicians issued from different departments and universities participated into the study. They received a file with clinical and biological data, iodine turnover rate, scintigraphic images and calculated thyroid surfaces from 10 patients (8 females, 2 males), 30-77 yrs suffering from hyperthyroidism of various etiologies: 7 patients had clinically overt hyperthyroidism and 3 subclinical hyperthyroidism; 7 patients had toxic goiters of various size (Graves' disease), 2 multi nodular goiter and 1 toxic nodule. None suffered from cardiac anomalies or ophthalmopathy. Participants were asked to define the amount of RI they would give in each case. Answers were received during a 8-week period. Analysing data from case 1 to case 10, the ranges of the proposed doses varied between 8 and 22 milli Curies (mCi) (sd : 2.4 - 6.07). Considering all the patients, the proposed doses varied between 2 mCi and 25 mCi. Analysing answers among the 21 participants, mean proposed doses varied between 4.5 and 17.3 mCi (sd: 0.69 - 7.99). Conclusion: These results demonstrate a wide variability among nuclear medicine physicians in the proposed RI doses and confirm that in Belgium there is no uniformity in the procedure used to determine the amount of RI to administer for various causes of hyperthyroidism. This emphasizes the notion that the determination of the amount of RI to be administered remains a matter of debate. (author)

  17. Evaluation of web-based, self-administered, graphical food frequency questionnaire.

    Science.gov (United States)

    Kristal, Alan R; Kolar, Ann S; Fisher, James L; Plascak, Jesse J; Stumbo, Phyllis J; Weiss, Rick; Paskett, Electra D

    2014-04-01

    Computer-administered food frequency questionnaires (FFQs) can address limitations inherent in paper questionnaires by allowing very complex skip patterns, portion size estimation based on food pictures, and real-time error checking. We evaluated a web-based FFQ, the Graphical Food Frequency System (GraFFS). Participants completed the GraFFS, six telephone-administered 24-hour dietary recalls over the next 12 weeks, followed by a second GraFFS. Participants were 40 men and 34 women, aged 18 to 69 years, living in the Columbus, OH, area. Intakes of energy, macronutrients, and 17 micronutrients/food components were estimated from the GraFFS and the mean of all recalls. Bias (second GraFFS minus recalls) was -9%, -5%, +4%, and -4% for energy and percentages of energy from fat, carbohydrate, and protein, respectively. De-attenuated, energy-adjusted correlations (intermethod reliability) between the recalls and the second GraFFS for fat, carbohydrate, protein, and alcohol were 0.82, 0.79, 0.67, and 0.90, respectively; for micronutrients/food components the median was 0.61 and ranged from 0.40 for zinc to 0.92 for beta carotene. The correlations between the two administrations of the GraFFS (test-retest reliability) for fat, carbohydrate, protein, and alcohol were 0.60, 0.63, 0.73, and 0.87, respectively; among micronutrients/food components the median was 0.67 and ranged from 0.49 for vitamin B-12 to 0.82 for fiber. The measurement characteristics of the GraFFS were at least as good as those reported for most paper FFQs, and its high intermethod reliability suggests that further development of computer-administered FFQs is warranted. Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  18. Taurine ameliorated thyroid function in rats co-administered with chlorpyrifos and lead.

    Science.gov (United States)

    Akande, Motunrayo Ganiyat; Shittu, Muftau; Uchendu, Chidiebere; Yaqub, Lukuman Surakat

    2016-12-01

    Chlorpyrifos is a widely used organophosphate insecticide for domestic, agricultural and industrial purposes. Lead is a toxic heavy metal and it is used for domestic and industrial purposes. Taurine is a semi essential amino acid with bioprotective properties. The aim of this study was to investigate the effects of taurine on thyroid function in Wistar rats co-administered with chlorpyrifos and lead. The rats were divided into 5 groups of 10 rats each. The first two groups were administered with distilled water and soya oil (1 ml/kg) respectively. The other groups received taurine (50 mg/kg), chlorpyrifos + lead [chlorpyrifos (4.25 mg/kg, 1/20 median lethal dose] and lead (233.25 mg/kg, 1/20 median lethal dose) and taurine + chlorpyrifos + lead respectively. The treatments were administered once daily by oral gavage for 16 weeks. The rats were euthanized after the completion of the study and the thyroid function and thyroid histoarchitecture were evaluated. The results revealed that co-administration of chlorpyrifos and lead to the rats induced perturbations in thyroid function and this was manifested by reductions in the concentrations of triiodothyronine and thyroxine, increased thyroid stimulating hormone concentration and degeneration of the follicular epithelia of the thyroid gland. Taurine alleviated the perturbations in thyroid function and improved thyroid gland histoarchitecture. The beneficial effects of taurine may be attributed to its ability to protect the body from toxicity and oxidative stress. Taurine may be useful for prophylaxis against disruptions in thyroid function in animals that are exposed to environmental chlorpyrifos and lead.

  19. The co-solvent Cremophor EL limits absorption of orally administered paclitaxel in cancer patients.

    Science.gov (United States)

    Malingré, M M; Schellens, J H; Van Tellingen, O; Ouwehand, M; Bardelmeijer, H A; Rosing, H; Koopman, F J; Schot, M E; Ten Bokkel Huinink, W W; Beijnen, J H

    2001-11-16

    The purpose of this study was to investigate the effect of the co-solvents Cremophor EL and polysorbate 80 on the absorption of orally administered paclitaxel. 6 patients received in a randomized setting, one week apart oral paclitaxel 60 mg m(-2) dissolved in polysorbate 80 or Cremophor EL. For 3 patients the amount of Cremophor EL was 5 ml m(-2), for the other three 15 ml m(-2). Prior to paclitaxel administration patients received 15 mg kg(-1) oral cyclosporin A to enhance the oral absorption of the drug. Paclitaxel formulated in polysorbate 80 resulted in a significant increase in the maximal concentration (C(max)) and area under the concentration-time curve (AUC) of paclitaxel in comparison with the Cremophor EL formulations (P = 0.046 for both parameters). When formulated in Cremophor EL 15 ml m(-2), paclitaxel C(max) and AUC values were 0.10 +/- 0.06 microM and 1.29 +/- 0.99 microM h(-1), respectively, whereas these values were 0.31 +/- 0.06 microM and 2.61 +/- 1.54 microM h(-1), respectively, when formulated in polysorbate 80. Faecal data revealed a decrease in excretion of unchanged paclitaxel for the polysorbate 80 formulation compared to the Cremophor EL formulations. The amount of paclitaxel excreted in faeces was significantly correlated with the amount of Cremophor EL excreted in faeces (P = 0.019). When formulated in Cremophor EL 15 ml m(-2), paclitaxel excretion in faeces was 38.8 +/- 13.0% of the administered dose, whereas this value was 18.3 +/-15.5% for the polysorbate 80 formulation. The results show that the co-solvent Cremophor EL is an important factor limiting the absorption of orally administered paclitaxel from the intestinal lumen. They highlight the need for designing a better drug formulation in order to increase the usefulness of the oral route of paclitaxel

  20. The King-Devick test as a concussion screening tool administered by sports parents.

    Science.gov (United States)

    Leong, D F; Balcer, L J; Galetta, S L; Liu, Z; Master, C L

    2014-02-01

    Sports-related concussion has received increasing awareness due to short- and long-term neurologic sequelae seen among athletes. The King-Devick (K-D) test captures impairment of eye movements and other correlates of suboptimal brain function. We investigated the K-D test as a screening for concussion when administered by layperson sports parents in a cohort of amateur boxers. The K-D test was administered pre-fight and post-fight by laypersons masked to the head trauma status of each athlete. Matches were watched over by a ringside physician and boxing trainer. Athletes with suspected head trauma received testing with the Military Acute Concussion Evaluation (MACE) by the ringside physician to determine concussion status. Athletes sustaining concussion were compared to the athletes screened using the K-D test. Post-fight K-D scores were lower (better) than the best baseline score (41 vs. 39.3 s, P=0.34, Wilcoxon signed-rank test), in the absence of concussion. One boxer sustained a concussion as determined by the ringside physician. This boxer was accurately identified by the layperson K-D testers due to a worsening in K-D test compared to baseline (3.2 seconds) and an increased number of errors. High levels of test-retest reliability were observed (intraclass correlation coefficient 0.90 [95% CI 0.84-0.97]). Additionally, 6 boxers who participated in multiple bouts showed no worsening of their K-D times further supporting that scores are not affected by the fatigue associated with sparring. The K-D test is a rapid sideline screening tool for concussion that can be effectively administered by non-medically trained laypersons.

  1. Sources of motivation and frustration among healthcare workers administering antiretroviral treatment for HIV in rural Zimbabwe.

    Science.gov (United States)

    Campbell, C; Scott, K; Madenhire, C; Nyamukapa, C; Gregson, S

    2011-07-01

    The roll-out of accessible and affordable antiretroviral (ARV) drugs for people living with HIV in low-income countries is drastically changing the nature of HIV-related healthcare. The Zimbabwean Ministry of Health has renewed efforts to make antiretroviral treatment (ART) for HIV free and publically available across the country. This paper describes the findings from a multi-method qualitative study including interviews and a focus group with healthcare workers (mostly nurses), totalling 25 participants, and field notes from over 100 hours of ethnographic observation in three rural Zimbabwean health centres. These health centres began providing free ARV drugs to HIV-positive people over one year prior to the research period. We examined sources of motivation and frustration among nurses administering ART in these resource-poor health centres. The findings suggest that healthcare workers administering ART in challenging circumstances are adept at drawing strength from the dramatic physical and emotional recoveries made possible by ART and from their personal memories of the suffering caused by HIV/AIDS among close friends or family. However, healthcare staff grappled with extreme resource shortages, which led to exhaustion and frustration. Surprisingly, only one year into ART provision, healthcare workers did not reference the professional challenges of their HIV work before ART became available, suggesting that medical breakthroughs such as ART rapidly come to be seen as a standard element of nursing. Our findings provide a basis for optimism that medical breakthroughs such as ART can reinvigorate healthcare workers in the short term. However, we caution that the daily challenges of nursing in poor environments, especially administering an ongoing and resource-intensive regime such as ART, must be addressed to enable nurses to continue delivering high-quality ART in sub-Saharan Africa.

  2. Influence of atipamezole on effects of midsacral subarachnoidally administered detomidine in mares.

    Science.gov (United States)

    Skarda, R T; Muir, W W

    1998-04-01

    To examine effects of atipamezole on detomidine midsacral subarachnoidally-induced analgesia, cardiovascular and respiratory activity, head ptosis, and position of pelvic limbs in healthy mares. 10 healthy mares. Using a randomized, blinded, crossover study design, mares received detomidine (0.03 mg/kg of body weight, diluted in 3 ml of CSF) midsacral subarachnoidally, followed by atipamezole (0.1 mg/kg [test]) or sterile saline (0.9% NaCl) solution (control), i.v. 61 minutes later and saline solution (3 ml, midsacral subarachnoidally) on a separate occasion, at least 2 weeks later. Analgesia was determined by lack of sensory perception to electrical stimulation at the perineal dermatome and no response to needle-prick stimulation extending from the coccygeal to T15 dermatomes. Arterial acid-base (pH, standard bicarbonate, and base excess values), gas tensions (PO2, PCO2), PCV, total solids concentration, heart and respiratory rates, rectal temperature, and arterial blood pressure were determined, and mares were observed for sweating and urination. Mean scores of perineal analgesia, head ptosis, position of pelvic limbs, and cardiovascular and respiratory data were compared for the 3-hour test period. Subarachnoidally administered detomidine induced perineal analgesia (mean +/- SD onset, 9.0 +/- 4.6 minutes; duration, 130 +/- 26 minutes), marked head ptosis, moderate changes in pelvic limb position, cardiovascular and respiratory depression, sweating in analgesic zones, and diuresis. Intravenously administered atipamezole significantly reduced mean scores of detomidine-induced perineal analgesia, head ptosis, pelvic limb position, sweating and diuresis; partially antagonized detomidine-induced bradycardia; and did not effect detomidine-induced bradypnea. Most effects of midsacral subarachnoidally administered detomidine, except bradycardia and bradypnea, were reversed by atipamezole (0.1 mg/kg, i.v.), indicating that most of the actions of detomidine were mediated

  3. Validity and reliability of a self-administered foot evaluation questionnaire (SAFE-Q).

    Science.gov (United States)

    Niki, Hisateru; Tatsunami, Shinobu; Haraguchi, Naoki; Aoki, Takafumi; Okuda, Ryuzo; Suda, Yasunori; Takao, Masato; Tanaka, Yasuhito

    2013-03-01

    The Japanese Society for Surgery of the Foot (JSSF) is developing a QOL questionnaire instrument for use in pathological conditions related to the foot and ankle. The main body of the outcome instrument (the Self-Administered Foot Evaluation Questionnaire, SAFE-Q version 2) consists of 34 questionnaire items, which provide five subscale scores (1: Pain and Pain-Related; 2: Physical Functioning and Daily Living; 3: Social Functioning; 4: Shoe-Related; and 5: General Health and Well-Being). In addition, the instrument has nine optional questionnaire items that provide a Sports Activity subscale score. The purpose of this study was to evaluate the test-retest reliability of the SAFE-Q. Version 2 of the SAFE-Q was administered to 876 patients and 491 non-patients, and the test-retest reliability was evaluated for 131 patients. In addition, the SF-36 questionnaire and the JSSF Scale scoring form were administered to all of the participants. Subscale scores were scaled such that the final sum of scores ranged between zero (least healthy) to 100 (healthiest). The intraclass correlation coefficients were larger than 0.7 for all of the scores. The means of the five subscale scores were between 60 and 75. The five subscales easily separated patients from non-patients. The coefficients for the correlations of the subscale scores with the scores on the JSSF Scale and the SF-36 subscales were all highly statistically significantly greater than zero (p valid and reliable. In the future, it will be beneficial to test the responsiveness of the SAFE-Q.

  4. PHARMACOKINETICS OF SINGLE-DOSE ORALLY ADMINISTERED CIPROFLOXACIN IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

    Science.gov (United States)

    Barbosa, Lorraine; Johnson, Shawn P; Papich, Mark G; Gulland, Frances

    2015-06-01

    Ciprofloxacin is commonly selected for clinical use due to its broad-spectrum efficacy and is a frequently administered antibiotic at The Marine Mammal Center, a marine mammal rehabilitation facility. Ciprofloxacin is used for treatment of California sea lions ( Zalophus californianus ) suffering from a variety of bacterial infections at doses extrapolated from other mammalian species. However, as oral absorption is variable both within and across species, a more accurate determination of appropriate dosage is needed to ensure effective treatment and avoid emergence of drug-resistant bacterial strains. A pharmacokinetic study was performed to assess plasma concentrations of ciprofloxacin in California sea lions after a single oral dose. Twenty healthy California sea lions received a single 10-mg/kg oral dose of ciprofloxacin administered in a herring fish. Blood was then collected at two of the following times from each individual: 0.5, 0.75, 1, 2, 4, 8, 10, 12, 18, and 24 hr postingestion. Plasma ciprofloxacin concentration was assessed via high-performance liquid chromatography. A population pharmacokinetics model demonstrated that an oral ciprofloxacin dose of 10 mg/kg achieved an area under the concentration vs. time curve of 6.01 μg hr/ml. Absorption was rapid, with ciprofloxacin detectable in plasma 0.54 hr after drug administration; absorption half-life was 0.09 hr. A maximum plasma concentration of 1.21 μg/ml was observed at 1.01 hr, with an elimination half-life of 3.09 hr. Ciprofloxacin administered orally at 10 mg/kg produced therapeutic antibacterial exposure for only some of the most susceptible bacterial organisms commonly isolated from California sea lions.

  5. Tissue distribution and excretion kinetics of orally administered silica nanoparticles in rats

    Science.gov (United States)

    Lee, Jeong-A; Kim, Mi-Kyung; Paek, Hee-Jeong; Kim, Yu-Ri; Kim, Meyoung-Kon; Lee, Jong-Kwon; Jeong, Jayoung; Choi, Soo-Jin

    2014-01-01

    Purpose The effects of particle size on the tissue distribution and excretion kinetics of silica nanoparticles and their biological fates were investigated following a single oral administration to male and female rats. Methods Silica nanoparticles of two different sizes (20 nm and 100 nm) were orally administered to male and female rats, respectively. Tissue distribution kinetics, excretion profiles, and fates in tissues were analyzed using elemental analysis and transmission electron microscopy. Results The differently sized silica nanoparticles mainly distributed to kidneys and liver for 3 days post-administration and, to some extent, to lungs and spleen for 2 days post-administration, regardless of particle size or sex. Transmission electron microscopy and energy dispersive spectroscopy studies in tissues demonstrated almost intact particles in liver, but partially decomposed particles with an irregular morphology were found in kidneys, especially in rats that had been administered 20 nm nanoparticles. Size-dependent excretion kinetics were apparent and the smaller 20 nm particles were found to be more rapidly eliminated than the larger 100 nm particles. Elimination profiles showed 7%–8% of silica nanoparticles were excreted via urine, but most nanoparticles were excreted via feces, regardless of particle size or sex. Conclusion The kidneys, liver, lungs, and spleen were found to be the target organs of orally-administered silica nanoparticles in rats, and this organ distribution was not affected by particle size or animal sex. In vivo, silica nanoparticles were found to retain their particulate form, although more decomposition was observed in kidneys, especially for 20 nm particles. Urinary and fecal excretion pathways were determined to play roles in the elimination of silica nanoparticles, but 20 nm particles were secreted more rapidly, presumably because they are more easily decomposed. These findings will be of interest to those seeking to predict

  6. Relative bioavailability of methadone hydrochloride administered in chewing gum and tablets

    DEFF Research Database (Denmark)

    Christrup, Lona Louring; Angelo, H.R.; Bonde, J.

    1990-01-01

    Methadone administered in chewing gum in doses of 16.7-22.6 mg to seven patients in a study using an open balanced cross-over design, was compared with 20 mg of methadone given perorally as tablets. There was no significant difference in the AUC/D obtained after administration of chewing gum...... and tablets (p>0.05). It is concluded that the chewing gum formulation should be considered for further testing with respect to suppression of abstinence syndrome in narcotic addicts....

  7. Relative bioavailability of methadone hydrochloride administered in chewing gum and tablets.

    Science.gov (United States)

    Christrup, L L; Angelo, H R; Bonde, J; Kristensen, F; Rasmussen, S N

    1990-01-01

    Methadone administered in chewing gum in doses of 16.7-22.6 mg to seven patients in a study using an open balanced cross-over design, was compared with 20 mg of methadone given perorally as tablets. There was no significant difference in the AUC/D obtained after administration of chewing gum and tablets (p greater than 0.05). It is concluded that the chewing gum formulation should be considered for further testing with respect to suppression of abstinence syndrome in narcotic addicts.

  8. Intestinal Microbiota in Pediatric Surgical Cases Administered Bifidobacterium Breve: A Randomized Controlled Trial.

    Science.gov (United States)

    Okazaki, Tadaharu; Asahara, Takashi; Yamataka, Atsuyuki; Ogasawara, Yuki; Lane, Geoffrey J; Nomoto, Koji; Nagata, Satoru; Yamashiro, Yuichiro

    2016-07-01

    The efficacy of perioperative probiotic administration has been reported in adults. We examined the effects of orally administered Bifidobacterium breve strain Yakult (BBG-01) on outcomes in pediatric surgical cases by assessing intestinal and blood microbiota. BBG-01 was well tolerated without adverse effects, and postoperative infectious complications were significantly decreased. Fecal analysis showed increased Bifidobacterium and decreased Enterobacteriaceae, Clostridium difficile, and Pseudomonas. Concentrations of fecal acetic acid were significantly increased, maintaining fecal pH at <7.0. The incidence of detecting bacteria in blood was significantly reduced. BBG-01 improved the intestinal environment, and may be implicated in suppressing bacterial translocation.

  9. Self-administered physical activity questionnaires for the elderly: a systematic review of measurement properties.

    Science.gov (United States)

    Forsén, Lisa; Loland, Nina Waaler; Vuillemin, Anne; Chinapaw, Mai J M; van Poppel, Mireille N M; Mokkink, Lidwine B; van Mechelen, Willem; Terwee, Caroline B

    2010-07-01

    To systematically review and appraise studies examining self-administered physical activity questionnaires (PAQ) for the elderly. This article is one of a group of four articles in Sports Medicine on the content and measurement properties of PAQs. LITERATURE SEARCH METHODOLOGY: Searches in PubMed, EMBASE and SportDiscu (until May 2009) on self-administered PAQ. Inclusion criteria were as follows: (i) the study examined (at least one of) the measurement properties of a self-administered PAQ; (ii) the questionnaire aimed to measure physical activity (PA) in older people; (iii) the average age of the study population was >55 years; (iv) the article was written in English. We excluded PA interviews, diaries and studies that evaluated the measurement properties of a self-administered PAQ in a specific population, such as patients. We used a standard checklist (qualitative attributes and measurement properties of PA questionnaires [QAPAQ]) for appraising the measurement properties of PAQs. Eighteen articles on 13 PAQs were reviewed, including 16 reliability analyses and 25 validity analyses (of which 15 were on construct validity, seven on health/functioning associations, two on known-groups validity and one on responsiveness). Many studies suffered from methodological flaws, e.g. too small sample size or inadequate time interval between test and retest. Three PAQs received a positive rating on reliability: IPAQ-C (International Physical Activity Questionnaire-Chinese), intraclass correlation coefficient (ICC) > or = 0.81; WHI-PAQ (Women's Health Initiative-PAQ), ICC = 0.76; and PASE (Physical Activity Scale for the Elderly), Pearson correlation coefficient (r) = 0.84. However, PASE was negatively rated on reliability in another study (ICC = 0.65). One PAQ received a positive rating on construct validity: PASE against Mini-Logger (r > 0.52), but PASE was negatively rated in another study against accelerometer and another PAQ, Spearman correlation coefficient = 0.17 and 0

  10. Effect of intranasally administered insulin on cerebral blood flow and perfusion

    DEFF Research Database (Denmark)

    Akintola, Abimbola A.; van Opstal, Anna M.; Westendorp, Rudi G.

    2017-01-01

    Insulin, a vasoactive modulator regulating peripheral and cerebral blood flow, has been consistently linked to aging and longevity. In this proof of principle study, using a randomized, double-blinded, placebo-controlled crossover design, we explored the effects of intranasally administered insulin...... labelling. Total flow through the major cerebropetal arteries was unchanged in both young and old. In the older participants, intranasal insulin compared to placebo increased perfusion through the occipital gray matter (65.2±11.0 mL/100g/min vs 61.2±10.1 mL/100g/min, P=0.001), and in the thalamus (68...

  11. 20 CFR 408.1235 - How does the State transfer funds to SSA to administer its recognition payment program?

    Science.gov (United States)

    2010-04-01

    ... administer its recognition payment program? 408.1235 Section 408.1235 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Federal Administration of State Recognition Payments § 408.1235 How does the State transfer funds to SSA to administer its recognition payment program...

  12. 40 CFR 147.2200 - State-administered program-Class I, III, IV, and V wells.

    Science.gov (United States)

    2010-07-01

    ... AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) STATE, TRIBAL, AND EPA-ADMINISTERED UNDERGROUND INJECTION... administered by the Railroad Commission of Texas. A program revision application for Class III brine mining..._regulations/ibr_locations.html. (1) Texas Statutory and Regulatory Requirements Applicable to the Underground...

  13. 38 CFR 21.21 - Election of benefits under education programs administered by the Department of Veterans Affairs.

    Science.gov (United States)

    2010-07-01

    ... § 21.21 Election of benefits under education programs administered by the Department of Veterans... education programs administered by VA must make an election of benefits between chapter 31 and any other VA... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Election of benefits...

  14. 8 CFR 337.2 - Oath administered by the Immigration and Naturalization Service or an Immigration Judge.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Oath administered by the Immigration and Naturalization Service or an Immigration Judge. 337.2 Section 337.2 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY NATIONALITY REGULATIONS OATH OF ALLEGIANCE § 337.2 Oath administered by the Immigration and...

  15. Validation of the Portuguese self-administered computerised 24-hour dietary recall among second-, third- and fourth-grade children

    Science.gov (United States)

    Current methods for assessing children's dietary intake, such as interviewer-administered 24-h dietary recall (24-h DR), are time consuming and resource intensive. Self-administered instruments offer a low-cost diet assessment method for use with children. The present study assessed the validity of ...

  16. 34 CFR 692.30 - How does a State administer its community service-learning job program?

    Science.gov (United States)

    2010-07-01

    ...-learning job program? 692.30 Section 692.30 Education Regulations of the Offices of the Department of... Administer Its Community Service-Learning Job Program? § 692.30 How does a State administer its community service-learning job program? (a)(1) Each year, a State may use up to 20 percent of its allotment for a...

  17. Molecular cloning and construction of the coding region for human acetylcholinesterase reveals a G + C-rich attenuating structure

    International Nuclear Information System (INIS)

    Soreq, H.; Ben-Aziz, R.; Prody, C.A.; Seidman, S.; Gnatt, A.; Neville, L.; Lieman-Hurwitz, J.; Lev-Lehman, E.; Ginzberg, D.; Lapidot-Lifson, Y.; Zakut, H.

    1990-01-01

    To study the primary structure of human acetylcholinesterase and its gene expression and amplification, cDNA libraries from human tissues expressing oocyte-translatable AcChoEase mRNA were constructed and screened with labeled oligodeoxynucleotide probes. Several cDNA clones were isolated that encoded a polypeptide with ≥50% identically aligned amino acids to Torpedo AcChoEase and human butyrylcholinesterase. However, these cDNA clones were all truncated within a 300-nucleotide-long G + C-rich region with a predicted pattern of secondary structure having a high Gibbs free energy downstream from the expected 5' end of the coding region. Screening of a genomic DNA library revealed the missing 5' domain. When ligated to the cDNA and constructed into a transcription vector, this sequence encoded a synthetic mRNA translated in microinjected oocytes into catalytically active AcChoEase with marked preference for acetylthiocholine over butyrylthiocholine as a substrate, susceptibility to inhibition by the AcChoEase inhibitor BW284C51, and resistance to the AcChoEase inhibitor tetraisopropylpyrophosphoramide. Blot hybridization of genomic DNA from different individuals carrying amplified AcChoEase genes revealed variable intensities and restriction patterns with probes from the regions upstream and downstream from the predicted G + C-rich structure. Thus, the human AcChoEase gene includes a putative G + C-rich attenuator domain and is subject to structural alterations in cases of AcChoEase gene amplification

  18. Test-retest repeatability of child's respiratory symptoms and perceived indoor air quality - comparing self- and parent-administered questionnaires.

    Science.gov (United States)

    Lampi, Jussi; Ung-Lanki, Sari; Santalahti, Päivi; Pekkanen, Juha

    2018-02-09

    Questionnaires can be used to assess perceived indoor air quality and symptoms in schools. Questionnaires for primary school aged children have traditionally been parent-administered, but self-administered questionnaires would be easier to administer and may yield as good, if not better, information. Our aim was to compare the repeatability of self- and parent-administered indoor air questionnaires designed for primary school aged pupils. Indoor air questionnaire with questions on child's symptoms and perceived indoor air quality in schools was sent to parents of pupils aged 7-12 years in two schools and again after two weeks. Slightly modified version of the questionnaire was administered to pupils aged 9-12 years in another two schools and repeated after a week. 351 (52%) parents and 319 pupils (86%) answered both the first and the second questionnaire. Test-retest repeatability was assessed with intra-class correlation (ICC) and Cohen's kappa coefficients (k). Test-retest repeatability was generally between 0.4-0.7 (ICC; k) in both self- and parent-administered questionnaire. In majority of the questions on symptoms and perceived indoor air quality test-retest repeatability was at the same level or slightly better in self-administered compared to parent-administered questionnaire. Agreement of self- and parent administered questionnaires was generally indoor air quality. Children aged 9-12 years can give as, or even more, repeatable information about their respiratory symptoms and perceived indoor air quality than their parents. Therefore, it may be possible to use self-administered questionnaires in future studies also with children.

  19. Vasopressin differentially modulates aggression and anxiety in adolescent hamsters administered anabolic steroids.

    Science.gov (United States)

    Morrison, Thomas R; Ricci, Lesley A; Melloni, Richard H

    2016-11-01

    Adolescent Syrian hamsters (Mesocricetus auratus) treated with anabolic/androgenic steroids display increased offensive aggression and decreased anxiety correlated with an increase in vasopressin afferent development, synthesis, and neural signaling within the anterior hypothalamus. Upon withdrawal from anabolic/androgenic steroids, this neurobehavioral relationship shifts as hamsters display decreased offensive aggression and increased anxiety correlated with a decrease in anterior hypothalamic vasopressin. This study investigated the hypothesis that alterations in anterior hypothalamic vasopressin neural signaling modulate behavioral shifting between adolescent anabolic/androgenic steroid-induced offensive aggression and anxiety. To test this, adolescent male hamsters were administered anabolic/androgenic steroids and tested for offensive aggression or anxiety following direct pharmacological manipulation of vasopressin V1A receptor signaling within the anterior hypothalamus. Blockade of anterior hypothalamic vasopressin V1A receptor signaling suppressed offensive aggression and enhanced general and social anxiety in hamsters administered anabolic/androgenic steroids during adolescence, effectively reversing the pattern of behavioral response pattern normally observed during the adolescent exposure period. Conversely, activation of anterior hypothalamic vasopressin V1A receptor signaling enhanced offensive aggression in hamsters exposed to anabolic/androgenic steroids during adolescence. Together, these findings suggest that the state of vasopressin neural development and signaling in the anterior hypothalamus plays an important role in behavioral shifting between aggression and anxiety following adolescent exposure to anabolic/androgenic steroids. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. A Population-Level Data Analytics Portal for Self-Administered Lifestyle and Mental Health Screening.

    Science.gov (United States)

    Zhang, Xindi; Warren, Jim; Corter, Arden; Goodyear-Smith, Felicity

    2016-01-01

    This paper describes development of a prototype data analytics portal for analysis of accumulated screening results from eCHAT (electronic Case-finding and Help Assessment Tool). eCHAT allows individuals to conduct a self-administered lifestyle and mental health screening assessment, with usage to date chiefly in the context of primary care waiting rooms. The intention is for wide roll-out to primary care clinics, including secondary school based clinics, resulting in the accumulation of population-level data. Data from a field trial of eCHAT with sexual health questions tailored to youth were used to support design of a data analytics portal for population-level data. The design process included user personas and scenarios, screen prototyping and a simulator for generating large-scale data sets. The prototype demonstrates the promise of wide-scale self-administered screening data to support a range of users including practice managers, clinical directors and health policy analysts.

  1. Ethical dilemmas faced by hospice nurses when administering palliative sedation to patients with terminal cancer.

    Science.gov (United States)

    De Vries, Kay; Plaskota, Marek

    2017-04-01

    Palliative sedation is a method of symptom management frequently used in hospices to treat uncontrolled symptoms at the end of life. There is a substantial body of literature on this subject; however, there has been little research into the experiences of hospice nurses when administering palliative sedation in an attempt to manage the terminal restlessness experienced by cancer patients. Semistructured interviews were conducted with a purposive sample of seven hospice nurses who had cared for at least one patient who had undergone palliative sedation within the past year in a hospice in the south of England in the United Kingdom. A phenomenological approach and Colaizzi's stages of analysis were employed to develop themes from the data. Facilitating a "peaceful death" was the primary goal of the nurses, where through the administration of palliative sedation they sought to enable and support patients to be "comfortable," "relaxed," and "calm" at the terminal stage of their illness. Ethical dilemmas related to decision making were a factor in achieving this. These were: medication decisions, "juggling the drugs," "causing the death," sedating young people, the family "requesting" sedation, and believing that hospice is a place where death is hastened. Hospice nurses in the U.K. frequently encounter ethical and emotional dilemmas when administering palliative sedation. Making such decisions about using palliative sedation causes general discomfort for them. Undertaking this aspect of care requires confidence and competence on the part of nurses, and working within a supportive hospice team is of fundamental importance in supporting this practice.

  2. Antibody production in rabbits administered Freund's complete adjuvant and carprofen concurrently.

    Science.gov (United States)

    Fishback, Joanna E; Stronsky, Sabrina M; Green, Catherine A; Bean, Krystal D; Froude, Jeffrey W

    2016-02-01

    Freund's complete adjuvant (FCA) is a commonly used immunopotentiator that can boost polyclonal antibody production in animal models such as rabbits, but FCA is also known to cause inflammation and pain. It is important to balance the welfare of animals with the goal of efficiently producing antibodies, but little is known about how common treatments for pain and inflammation, such as non-steroidal anti-inflammatory drugs (NSAIDs), affect the production of polyclonal antibodies. The purpose of this study was to measure polyclonal antibody production in rabbits that were administered FCA either with or without a concurrent treatment of a NSAID, carprofen. Rabbits were divided into two groups and were administered identical treatments of an antigen with adjuvant, and the treatment group also received carprofen injections at different stages of the study. Carprofen treatment did not significantly affect polyclonal antibody production, which suggests that carprofen and other NSAIDs can be used alongside FCA in rabbits to achieve desired levels of antibody production while minimizing pain and distress associated with the use of FCA.

  3. Acute toxicity of subcutaneously administered vitamin E isomers delta- and gamma-tocotrienol in mice.

    Science.gov (United States)

    Swift, Sibyl N; Pessu, Roli L; Chakraborty, Kushal; Villa, Vilmar; Lombardini, Eric; Ghosh, Sanchita P

    2014-01-01

    The toxicity of parenterally administered vitamin E isomers, delta-tocotrienol (DT3) and gamma-tocotrienol (GT3), was evaluated in male and female CD2F1 mice. In an acute toxicity study, a single dose of DT3 or GT3 was administered subcutaneously in a dose range of 200 to 800 mg/kg. A mild to moderately severe dermatitis was observed clinically and microscopically in animals at the injection site at doses above 200 mg/kg. The severity of the reaction was reduced when the drug concentration was lowered. Neither drug produced detectable toxic effects in any other tissue at the doses tested. Based on histopathological analysis for both DT3 and GT3, and macroscopic observations of inflammation at the injection site, a dose of 300 mg/kg was selected as the lowest toxic dose in a 30-day toxicity study performed in male mice. At this dose, a mild skin irritation occurred at the injection site that recovered completely by the end of the experimental period. At a dose of 300 mg/kg of DT3 or GT3, no adverse effects were observed in any tissues or organs. © The Author(s) 2014.

  4. Tolerability assessment of a lectin fraction from Tepary bean seeds (Phaseolus acutifolius orally administered to rats

    Directory of Open Access Journals (Sweden)

    Roberto Ferriz-Martínez

    2015-01-01

    Full Text Available Our previous studies have shown that a lectin rich fraction (TBLF extracted from Tepary bean seeds differentially inhibits cancer cells proliferation in vitro. Before testing the in vivo anticancer effect, the acute and subchronic toxicological assays in rats were conducted, where an oral dose of 50 mg/body weight kg was determined as the NOAEL. This study evaluated the resistance to digestion and complete blood count (CBC after 24 h of the orally administered 50 mg/kg TBLF. The digestion resistance test showed lectins activity retention after 72 h and the CBC study showed a high level of eosinophils, suggesting an allergic-like response. Tolerability was assayed after 6 weeks of treatment by dosing with an intragastric cannula every third day per week. It was observed a transient reduction in food intake and body weight in the first weeks, resulting in body weight gain reduction of 10% respect to the control group at the end of the study. Additionally, organs weight, histopathological analysis and blood markers for nutritional status and for liver, pancreas and renal function were not affected. Our results suggest that 50 mg/kg TBLF administered by oral route, exhibit no toxicity in rats and it was well tolerated. Further studies will focus on long-term studies.

  5. Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumors in mice.

    Directory of Open Access Journals (Sweden)

    Iraklis C Kourtis

    Full Text Available Nanoparticles have been extensively developed for therapeutic and diagnostic applications. While the focus of nanoparticle trafficking in vivo has traditionally been on drug delivery and organ-level biodistribution and clearance, recent work in cancer biology and infectious disease suggests that targeting different cells within a given organ can substantially affect the quality of the immunological response. Here, we examine the cell-level biodistribution kinetics after administering ultrasmall Pluronic-stabilized poly(propylene sulfide nanoparticles in the mouse. These nanoparticles depend on lymphatic drainage to reach the lymph nodes and blood, and then enter the spleen rather than the liver, where they interact with monocytes, macrophages and myeloid dendritic cells. They were more readily taken up into lymphatics after intradermal (i.d. compared to intramuscular administration, leading to ∼50% increased bioavailability in blood. When administered i.d., their distribution favored antigen-presenting cells, with especially strong targeting to myeloid cells. In tumor-bearing mice, the monocytic and the polymorphonuclear myeloid-derived suppressor cell compartments were efficiently and preferentially targeted, rendering this nanoparticulate formulation potentially useful for reversing the highly suppressive activity of these cells in the tumor stroma.

  6. Telephone-administered psychotherapy for depression in MS patients: moderating role of social support.

    Science.gov (United States)

    Beckner, Victoria; Howard, Isa; Vella, Lea; Mohr, David C

    2010-02-01

    Depression is common in individuals with multiple sclerosis (MS). While psychotherapy is an effective treatment for depression, not all individuals benefit. We examined whether baseline social support might differentially affect treatment outcome in 127 participants with MS and depression randomized to either Telephone-administered Cognitive-Behavioral Therapy (T-CBT) or Telephone-administered Emotion-Focused Therapy (T-EFT). We predicted that those with low social support would improve more in T-EFT, since this approach emphasizes the therapeutic relationship, while participants with strong social networks and presumably more emotional resources might fare better in the more structured and demanding T-CBT. We found that both level of received support and satisfaction with that support at baseline did moderate treatment outcome. Individuals with high social support showed a greater reduction in depressive symptoms in the T-CBT as predicted, but participants with low social support showed a similar reduction in both treatments. This suggests that for participants with high social support, CBT may be a more beneficial treatment for depression compared with EFT.

  7. Assessing smoking status in disadvantaged populations: is computer administered self report an accurate and acceptable measure?

    Directory of Open Access Journals (Sweden)

    Bryant Jamie

    2011-11-01

    Full Text Available Abstract Background Self report of smoking status is potentially unreliable in certain situations and in high-risk populations. This study aimed to determine the accuracy and acceptability of computer administered self-report of smoking status among a low socioeconomic (SES population. Methods Clients attending a community service organisation for welfare support were invited to complete a cross-sectional touch screen computer health survey. Following survey completion, participants were invited to provide a breath sample to measure exposure to tobacco smoke in expired air. Sensitivity, specificity, positive predictive value and negative predictive value were calculated. Results Three hundred and eighty three participants completed the health survey, and 330 (86% provided a breath sample. Of participants included in the validation analysis, 59% reported being a daily or occasional smoker. Sensitivity was 94.4% and specificity 92.8%. The positive and negative predictive values were 94.9% and 92.0% respectively. The majority of participants reported that the touch screen survey was both enjoyable (79% and easy (88% to complete. Conclusions Computer administered self report is both acceptable and accurate as a method of assessing smoking status among low SES smokers in a community setting. Routine collection of health information using touch-screen computer has the potential to identify smokers and increase provision of support and referral in the community setting.

  8. Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumors in mice.

    Science.gov (United States)

    Kourtis, Iraklis C; Hirosue, Sachiko; de Titta, Alexandre; Kontos, Stephan; Stegmann, Toon; Hubbell, Jeffrey A; Swartz, Melody A

    2013-01-01

    Nanoparticles have been extensively developed for therapeutic and diagnostic applications. While the focus of nanoparticle trafficking in vivo has traditionally been on drug delivery and organ-level biodistribution and clearance, recent work in cancer biology and infectious disease suggests that targeting different cells within a given organ can substantially affect the quality of the immunological response. Here, we examine the cell-level biodistribution kinetics after administering ultrasmall Pluronic-stabilized poly(propylene sulfide) nanoparticles in the mouse. These nanoparticles depend on lymphatic drainage to reach the lymph nodes and blood, and then enter the spleen rather than the liver, where they interact with monocytes, macrophages and myeloid dendritic cells. They were more readily taken up into lymphatics after intradermal (i.d.) compared to intramuscular administration, leading to ∼50% increased bioavailability in blood. When administered i.d., their distribution favored antigen-presenting cells, with especially strong targeting to myeloid cells. In tumor-bearing mice, the monocytic and the polymorphonuclear myeloid-derived suppressor cell compartments were efficiently and preferentially targeted, rendering this nanoparticulate formulation potentially useful for reversing the highly suppressive activity of these cells in the tumor stroma.

  9. Effect of administering a diet contamined with fumonisins on the kidneys of wistar rats

    Directory of Open Access Journals (Sweden)

    Jade Cabestre Venancio

    2014-08-01

    Full Text Available Fumonisins (FBs are mycotoxins produced by Fusarium molds. Several works have shown contamination of maize by this toxin. Fumonisin B1 (FB-1 is found in greatest proportion (about 70%, resistant to several industrialization processes. In that context, the objective of this work was to analyze the effect of administering a diet contaminated with FB-1 on the morphophysiology of the kidneys of 21-day old male Wistar rats. The animals were divided into 2 groups: G0 (with animals receiving feed free of FBs and G6 (6mg of FB1 kg-1 of feed. The diet was administered during 42 days. After that period, the animals were placed in metabolic cages for urine collection, blood was collected for analysis of plasma creatinine, and the kidneys were fixed and stained with Masson's trichrome. We observed that FB1 administration did not affect feed intake, body weight gain and animal growth. The normal levels of plasma creatinine suggest that the toxin did not lead to glomerular lesion. There was also no change in water intake, osmolarity and excretion of sodium in urine. However, there was a significant increase in urine volume and potassium excretion in urine, with mild tubulointerstitial changes in the outer cortex for the group receiving the mycotoxin.

  10. Effect of sulfonylureas administered centrally on the blood glucose level in immobilization stress model.

    Science.gov (United States)

    Sharma, Naveen; Sim, Yun-Beom; Park, Soo-Hyun; Lim, Su-Min; Kim, Sung-Su; Jung, Jun-Sub; Hong, Jae-Seung; Suh, Hong-Won

    2015-05-01

    Sulfonylureas are widely used as an antidiabetic drug. In the present study, the effects of sulfonylurea administered supraspinally on immobilization stress-induced blood glucose level were studied in ICR mice. Mice were once enforced into immobilization stress for 30 min and returned to the cage. The blood glucose level was measured 30, 60, and 120 min after immobilization stress initiation. We found that intracerebroventricular (i.c.v.) injection with 30 µg of glyburide, glipizide, glimepiride or tolazamide attenuated the increased blood glucose level induced by immobilization stress. Immobilization stress causes an elevation of the blood corticosterone and insulin levels. Sulfonylureas pretreated i.c.v. caused a further elevation of the blood corticosterone level when mice were forced into the stress. In addition, sulfonylureas pretreated i.c.v. alone caused an elevation of the plasma insulin level. Furthermore, immobilization stress-induced insulin level was reduced by i.c.v. pretreated sulfonylureas. Our results suggest that lowering effect of sulfonylureas administered supraspinally against immobilization stress-induced increase of the blood glucose level appears to be primarily mediated via elevation of the plasma insulin level.

  11. Supraspinally-administered agmatine attenuates the development of oral fentanyl self-administration

    Science.gov (United States)

    Wade, Carrie L.; Schuster, Daniel J.; Domingo, Kristine M.; Kitto, Kelley F.; Fairbanks, Carolyn A.

    2009-01-01

    The decarboxylation product of arginine, agmatine, has effectively reduced or prevented opioid-induced tolerance and dependence when given either systemically (intraperitoneally or subcutaneously) or centrally (intrathecally or intracerebroventricularly). Systemically administered agmatine also reduces the escalation phase of intravenous fentanyl self-administration in rats. The present study assessed whether centrally (intracerebroventricular, i.c.v.) delivered agmatine could prevent the development of fentanyl self-administration in mice. Mice were trained to respond under a fixed-ratio 1 (FR1) schedule for either fentanyl (0.7 μg/70 μl, p.o.) or food reinforcement. Agmatine (10 nmol/5 μl), injected i.c.v. 12-14h before the first session and every other evening (12-14h before session) for 2 weeks, completely attenuated oral fentanyl self-administration (but not food-maintained responding) compared to saline-injected controls. When agmatine was administered after fentanyl self-administration had been established (day 8) it had no attenuating effects on bar pressing. This dose of agmatine does not decrease locomotor activity as assessed by rotarod. The present findings significantly extend the previous observation that agmatine prevents opioid-maintained behavior to a chronic model of oral fentanyl self-administration as well as identifying a supraspinal site of action for agmatine inhibition of drug addiction. PMID:18495108

  12. The effect of training administered to working mothers on maternal anxiety levels and breastfeeding habits.

    Science.gov (United States)

    Çiftçi, Esra K; Arikan, Duygu

    2012-08-01

    This study was conducted to determine the effect of training administered to working mothers and its duration on maternal anxiety levels and breastfeeding habits. Within the scope of Health for All in the 21st Century project, a goal was set to increase the rate of infants fed exclusively by breastfeeding during the first six months of life to 80% by the year 2015. A randomised design with repeated measures. During collection of pretest data, a Personal Information Form, a Questionnaire Form and a State Trait Anxiety Inventory were administered to the mothers in the experimental and control groups. Five home visits were conducted starting two weeks before the date when mothers returned to work and ending when the infants became six months old. Breastfeeding techniques were taught to these mothers. Data were subjected to Proc MEAN, FREQ, anova and GENMOD procedures. The rate of natural feeding (breastfeeding exclusively) among trained mothers was greater than untrained mothers. The frequency of breastfeeding affects maternal anxiety levels; the anxiety level of mothers decreased with increasing frequency of breastfeeding. Educating working mothers about breastfeeding reduces their anxiety levels and influences positively their breastfeeding habits. With the support of health-care staff to increase awareness and knowledge on the value and sufficiency of breast milk, the rate and period of natural feeding increased significantly among working mothers. © 2011 Blackwell Publishing Ltd.

  13. The effects of four different drugs administered through catheters on slime production in coagulase negative Staphylococci

    Directory of Open Access Journals (Sweden)

    J. Sedef Göçmen

    2012-12-01

    Full Text Available Objectives: Higher rate of slime production has been found in pathogen bacteria strains. Accordingly, the factors thatcontribute to higher slime production rate increase the infection risk, while the factors that reduce the slime productionrate will reduce the infection risk. The effect of some drugs that are administered through catheters in intensive careunits on slime production with coagulase negative Staphylococci was investigated.Materials and methods: In this study, the effect of four different preparations containing Glyceryl trinitrate (Perlinganit®, Dexmedetomidine (Precedex®, Esmolol (Brevibloc®, and Propofol (Propofol® on slime production of 24Staphylococcus epidermidis strains isolated from blood cultures of patients, and reference strain were investigated. Slimeproduction was determined using ‘the quantitative microdilution plaque test’ described by Christensen.Results: Under controlled medium, eight strains formed slimes, and in the media containing esmolol, glyceryl trinitrate,dexmedetomidine, and propofol slimes were positive for five, 21, 15, and 18 strains, respectively. The rate of slime productionin glyceryl trinitrate, dexmedetomidine, and propofol containing media were higher than that of the controls.Conclusions: In the light of the results of this study, it is concluded that the drugs and/or additives increase the rate ofslime production. The effects of the preparations administered through catheters on slime production should be investigated,and these effects should be kept in mind during their use. J Microbiol Infect Dis 2012; 2(4: 150-154Key words: Slime Production, Coagulase Negative Staphyloccoci, Parenteral drugs

  14. Self-administered health literacy instruments for people with diabetes: systematic review of measurement properties.

    Science.gov (United States)

    Lee, Eun-Hyun; Kim, Chun-Ja; Lee, Jiyeon; Moon, Seung Hei

    2017-09-01

    The aims of this study were to identify all available self-administered instruments measuring health literacy in people with diabetes and to determine the current instrument that is the most appropriate for applying to this population in both practice and research. A systematic review of measurement properties. MEDLINE, EMBASE and CINAHL electronic databases from their inception up to 28 March 2016. The methodological quality of each included study was assessed using the COnsensus-based Standards for the selection of health Measurement INstruments checklist. The reported results for measurement properties in the studies were assessed according to Terwee's quality criteria. Thirteen self-administered instruments measuring health literacy in people with diabetes were identified, of which six (44%) were diabetes-specific instruments. The instruments that covered the broadest contents of health literacy were the Health Literacy Scale and Health Literacy Questionnaire. The (test-retest) reliability, measurement error and responsiveness were not evaluated for any instrument, while internal consistency and hypothesis testing validity were the most frequently assessed measurement properties. With the current evidence, the Health Literacy Scale may be the most appropriate instrument for patients with diabetes in practice and research. However, the structural validity of this scale needs to be further established, particularly in other language versions. It is also recommended to use the Diabetes Numeracy Test-15 along with the Health Literacy Scale to complement the lack of numeracy measures in the Health Literacy Scale. © 2017 John Wiley & Sons Ltd.

  15. The problem of bias when nursing facility staff administer customer satisfaction surveys.

    Science.gov (United States)

    Hodlewsky, R Tamara; Decker, Frederic H

    2002-10-01

    Customer satisfaction instruments are being used with increasing frequency to assess and monitor residents' assessments of quality of care in nursing facilities. There is no standard protocol, however, for how or by whom the instruments should be administered when anonymous, written responses are not feasible. Researchers often use outside interviewers to assess satisfaction, but cost considerations may limit the extent to which facilities are able to hire outside interviewers on a regular basis. This study was designed to investigate the existence and extent of any bias caused by staff administering customer satisfaction surveys. Customer satisfaction data were collected in 1998 from 265 residents in 21 nursing facilities in North Dakota. Half the residents in each facility were interviewed by staff members and the other half by outside consultants; scores were compared by interviewer type. In addition to a tabulation of raw scores, ordinary least-squares analysis with facility fixed effects was used to control for resident characteristics and unmeasured facility-level factors that could influence scores. Significant positive bias was found when staff members interviewed residents. The bias was not limited to questions directly affecting staff responsibilities but applied across all types of issues. The bias was robust under varying constructions of satisfaction and dissatisfaction. A uniform method of survey administration appears to be important if satisfaction data are to be used to compare facilities. Bias is an important factor that should be considered and weighed against the costs of obtaining outside interviewers when assessing customer satisfaction among long term care residents.

  16. Hemato-biochemical responses to packing in donkeys administered ascorbic acid during the harmattan season.

    Science.gov (United States)

    Olaifa, Folashade; Ayo, Joseph Olusegun; Ambali, Suleiman Folorunsho; Rekwot, Peter Ibrahim

    2015-02-01

    Experiments were performed to investigate the effect of ascorbic acid (AA) in reducing hemato-biochemical changes in pack donkeys during the cold-dry (harmattan) season. Six experimental donkeys administered orally AA (200 mg/kg) and six control donkeys not administered ascorbic acid were subjected to packing. Blood samples were collected from all donkeys for hematological and biochemical analyses. In the control donkeys, packed cell volume (PCV), erythrocyte count and hemoglobin concentration (Hb) decreased significantly (Pdonkeys, there was no significant difference between the pre- and post-packing values of PCV, erythrocyte count and Hb. In the control donkeys, the neutrophil and neutrophil:lymphocyte ratio increased significantly (Pdonkeys, the pre- and post-packing values were not significantly different. The eosinophil count increased significantly (Pdonkeys post packing. In conclusion, packing exerted significant adverse effects on the hematological parameters ameliorated by AA administration. AA may modulate neutrophilia and induce a considerable alteration of erythroid markers in donkeys subjected to packing during the harmattan season.

  17. Success rates of the first inferior alveolar nerve block administered by dental practitioners.

    Science.gov (United States)

    Kriangcherdsak, Yutthasak; Raucharernporn, Somchart; Chaiyasamut, Teeranut; Wongsirichat, Natthamet

    2016-06-01

    Inferior alveolar nerve block (IANB) of the mandible is commonly used in the oral cavity as an anesthetic technique for dental procedures. This study evaluated the success rate of the first IANB administered by dental practitioners. Volunteer dental practitioners at Mahidol University who had never performed an INAB carried out 106 INAB procedures. The practitioners were divided into 12 groups with their advisors by randomized control trials. We recorded the success rate via pain visual analog scale (VAS) scores. A large percentage of the dental practitioners (85.26%) used the standard method to locate the anatomical landmarks, injecting the local anesthetic at the correct position, with the barrel of the syringe parallel to the occlusal plane of the mandibular teeth. Further, 68.42% of the dental practitioners injected the local anesthetic on the right side by using the left index finger for retraction. The onset time was approximately 0-5 mins for nearly half of the dental practitioners (47.37% for subjective onset and 43.16% for objective onset), while the duration of the IANB was approximately 240-300 minutes (36.84%) after the initiation of numbness. Moreover, the VAS pain scores were 2.5 ± 1.85 and 2.1 ± 1.8 while injecting and delivering local anesthesia, respectively. The only recorded factor that affected the success of the local anesthetic was the administering practitioner. This reinforces the notion that local anesthesia administration is a technique-sensitive procedure.

  18. Blood and tissue tocopherol levels in rats following intraperitoneally administered alpha-tocopheryl acetate.

    Science.gov (United States)

    McGee, C D; Greenwood, C E; Jeejeebhoy, K N

    1990-01-01

    The correction or maintenance of blood and tissue alpha-tocopherol (alpha-Toc) levels by intraperitoneally administered all-rac-alpha-tocopheryl acetate (alpha-Tac) was compared with RRR- alpha-tocopherol (alpha-Toc) in vitamin E-depleted and control rats. Rats received 1.3 TE vitamin E daily for 7 days. alpha-Tac was detected in plasma of one-third of alpha-Tac-treated rats 24 hr after the first treatment, although not in subsequent samplings. Both alpha-Tac and alpha-Toc increased tocopherol levels in plasma and liver of E-deprived rats, while little or no change was observed in adipose tissue and brain. Similarly, control rats treated with alpha-Tac or alpha-Toc had significantly greater (p less than 0.05) plasma and liver alpha-Toc levels at day 3 and day 7 than did saline-treated rats. There was no significant difference in adipose alpha-Toc levels among treatment groups of control rats. The results of this study suggest that alpha-Tac is rapidly hydrolyzed to its biologically active alcohol form and results in similar effects to that of intraperitoneally administered alpha-Toc.

  19. Bioavailability of detomidine administered sublingually to horses as an oromucosal gel.

    Science.gov (United States)

    Kaukinen, H; Aspegrén, J; Hyyppä, S; Tamm, L; Salonen, J S

    2011-02-01

    The objective of the study was to determine the absorption, bioavailability and sedative effect of detomidine administered to horses as an oromucosal gel compared to intravenous and intramuscular administration of detomidine injectable solution. The study was open and randomized, with three sequences crossover design. Nine healthy horses were given 40 μg/kg detomidine intravenously, intramuscularly or administered under the tongue with a 7-day wash-out period between treatments. Blood samples were collected before and after drug administration for the measurement of detomidine concentrations in serum. The effects of the route of administration on heart rate and rhythm were evaluated and the depth of sedation assessed. Mean (±SD) bioavailability of detomidine was 22% (±5.3%) after sublingual administration and 38.2% (±7.9%) after intramuscular administration. The sedative effects correlated with detomidine concentrations regardless of the route of administration. We conclude that less detomidine is absorbed when given sublingually than when given intramuscularly, because part of it does not reach the circulation. Sublingual administration of detomidine oromucosal gel at 40 μg/kg produces safe sedation in horses. Slow absorption leads to fewer and less pronounced adverse effects than the more rapid absorption after intramuscular injection. © 2010 Blackwell Publishing Ltd.

  20. Preliminary results of the analysis of the administered activities in diagnostic studies of nuclear medicine

    International Nuclear Information System (INIS)

    Lopez Bejerano, G.; Sed, L.J.

    2001-01-01

    The worldwide use of Nuclear Medicine diagnostic procedures and the tendency to its increment, infers an important exposure of the population to ionising radiation; it has motivated that the IAEA in the International Basic Safety Standards (BSS), emits recommendations for the establishment of guidance levels of activities administered to the patients in diagnostic procedures. Taking into account the above-mentioned and that in Cuba there exist 20 departments of Nuclear Medicine that in the majority possess equipment with more than 20 years of operation, which influences directly the medical exposure. A survey was designed and applied in 10 of these departments. The survey evaluates the compliance with the BSS requirements, and specifically, the activities administered to the patients in Nuclear Medicine diagnostic procedures are analysed. In the present work the obtained preliminary results of the statistical analysis carried out on the activity values used in Nuclear Medicine departments are presented, and comparisons made for a proposal of guidance levels for the national practice, which is compared with those recommended internationally. (author)

  1. Alteration of intestinal microbiota in mice orally administered with salmon cartilage proteoglycan, a prophylactic agent.

    Directory of Open Access Journals (Sweden)

    Krisana Asano

    Full Text Available Proteoglycan (PG extracted from salmon nasal cartilage has potential to be a prophylactic agent. Daily oral administration of the PG attenuates systemic inflammatory response in the experimental mouse models. In this study, we applied the culture-independent approach to investigate an alteration of intestinal microbiota composition in PG-administered mice. The results indicated that the population level of bacilli increased in the small and large intestine upon PG administration. On the other hand, the population level of clostridia decreased in the large intestine. The proportion of bacteria that are able to ferment saccharides and produce short-chain fatty acids increased in the small intestine and decreased in the large intestine. Importantly, population level of probiotic lactobacilli and bacteria exhibiting the immunomodulatory effect increased in the PG-administered mice. In addition, several disease-associated bacteria decreased upon PG administration. These results provided an understanding of the specific role of PG involved in host immune modulation and supported our hypothesis that daily oral administration of PG improves the overall balance in composition of the intestinal microbial community.

  2. Evaluation of scanning 2D barcoded vaccines to improve data accuracy of vaccines administered.

    Science.gov (United States)

    Daily, Ashley; Kennedy, Erin D; Fierro, Leslie A; Reed, Jenica Huddleston; Greene, Michael; Williams, Warren W; Evanson, Heather V; Cox, Regina; Koeppl, Patrick; Gerlach, Ken

    2016-11-11

    Accurately recording vaccine lot number, expiration date, and product identifiers, in patient records is an important step in improving supply chain management and patient safety in the event of a recall. These data are being encoded on two-dimensional (2D) barcodes on most vaccine vials and syringes. Using electronic vaccine administration records, we evaluated the accuracy of lot number and expiration date entered using 2D barcode scanning compared to traditional manual or drop-down list entry methods. We analyzed 128,573 electronic records of vaccines administered at 32 facilities. We compared the accuracy of records entered using 2D barcode scanning with those entered using traditional methods using chi-square tests and multilevel logistic regression. When 2D barcodes were scanned, lot number data accuracy was 1.8 percentage points higher (94.3-96.1%, Pmanufacturer, month vaccine was administered, and vaccine type were associated with variation in accuracy for both lot number and expiration date. Two-dimensional barcode scanning shows promise for improving data accuracy of vaccine lot number and expiration date records. Adapting systems to further integrate with 2D barcoding could help increase adoption of 2D barcode scanning technology. Published by Elsevier Ltd.

  3. Antiviral Biologic Produced in DNA Vaccine/Goose Platform Protects Hamsters Against Hantavirus Pulmonary Syndrome When Administered Post-exposure.

    Directory of Open Access Journals (Sweden)

    Nicole Haese

    Full Text Available Andes virus (ANDV and ANDV-like viruses are responsible for most hantavirus pulmonary syndrome (HPS cases in South America. Recent studies in Chile indicate that passive transfer of convalescent human plasma shows promise as a possible treatment for HPS. Unfortunately, availability of convalescent plasma from survivors of this lethal disease is very limited. We are interested in exploring the concept of using DNA vaccine technology to produce antiviral biologics, including polyclonal neutralizing antibodies for use in humans. Geese produce IgY and an alternatively spliced form, IgYΔFc, that can be purified at high concentrations from egg yolks. IgY lacks the properties of mammalian Fc that make antibodies produced in horses, sheep, and rabbits reactogenic in humans. Geese were vaccinated with an ANDV DNA vaccine encoding the virus envelope glycoproteins. All geese developed high-titer neutralizing antibodies after the second vaccination, and maintained high-levels of neutralizing antibodies as measured by a pseudovirion neutralization assay (PsVNA for over 1 year. A booster vaccination resulted in extraordinarily high levels of neutralizing antibodies (i.e., PsVNA80 titers >100,000. Analysis of IgY and IgYΔFc by epitope mapping show these antibodies to be highly reactive to specific amino acid sequences of ANDV envelope glycoproteins. We examined the protective efficacy of the goose-derived antibody in the hamster model of lethal HPS. α-ANDV immune sera, or IgY/IgYΔFc purified from eggs, were passively transferred to hamsters subcutaneously starting 5 days after an IM challenge with ANDV (25 LD50. Both immune sera, and egg-derived purified IgY/IgYΔFc, protected 8 of 8 and 7 of 8 hamsters, respectively. In contrast, all hamsters receiving IgY/IgYΔFc purified from normal geese (n=8, or no-treatment (n=8, developed lethal HPS. These findings demonstrate that the DNA vaccine/goose platform can be used to produce a candidate antiviral

  4. Tissue distribution and excretion kinetics of orally administered silica nanoparticles in rats

    Directory of Open Access Journals (Sweden)

    Lee JA

    2014-12-01

    Full Text Available Jeong-A Lee,1 Mi-Kyung Kim,1 Hee-Jeong Paek,1 Yu-Ri Kim,2 Meyoung-Kon Kim,2 Jong-Kwon Lee,3 Jayoung Jeong,3 Soo-Jin Choi1 1Department of Food Science and Technology, Seoul Women’s University, Seoul, Republic of Korea; 2Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, Republic of Korea; 3Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungchungbuk–do, Republic of Korea Purpose: The effects of particle size on the tissue distribution and excretion kinetics of silica nanoparticles and their biological fates were investigated following a single oral administration to male and female rats. Methods: Silica nanoparticles of two different sizes (20 nm and 100 nm were orally administered to male and female rats, respectively. Tissue distribution kinetics, excretion profiles, and fates in tissues were analyzed using elemental analysis and transmission electron microscopy. Results: The differently sized silica nanoparticles mainly distributed to kidneys and liver for 3 days post-administration and, to some extent, to lungs and spleen for 2 days post-administration, regardless of particle size or sex. Transmission electron microscopy and energy dispersive spectroscopy studies in tissues demonstrated almost intact particles in liver, but partially decomposed particles with an irregular morphology were found in kidneys, especially in rats that had been administered 20 nm nanoparticles. Size-dependent excretion kinetics were apparent and the smaller 20 nm particles were found to be more rapidly eliminated than the larger 100 nm particles. Elimination profiles showed 7%–8% of silica nanoparticles were excreted via urine, but most nanoparticles were excreted via feces, regardless of particle size or sex. Conclusion: The kidneys, liver, lungs, and spleen were found to be the target organs of orally-administered silica nanoparticles in rats, and this organ

  5. How do patients with inflammatory bowel disease want their biological therapy administered?

    LENUS (Irish Health Repository)

    Allen, Patrick B

    2010-01-01

    BACKGROUND: Infliximab is usually administered by two monthly intravenous (iv) infusions, therefore requiring visits to hospital. Adalimumab is administered by self subcutaneous (sc) injections every other week. Both of these anti-TNF drugs appear to be equally efficacious in the treatment of Crohn\\'s Disease and therefore the decision regarding which drug to choose will depend to some extent on patient choice, which may be based on the mode of administration.The aims of this study were to compare preferences in Inflammatory Bowel Disease (IBD) patients for two currently available anti-TNF agents and the reasons for their choices. METHODS: An anonymous questionnaire was distributed to IBD patients who had attended the Gastroenterology service (Ulster Hospital, Dundonald, Belfast, N. Ireland. UK) between January 2007 and December 2007. The patients were asked in a hypothetical situation if the following administering methods of anti-TNF drugs (intravenous or subcutaneous) were available, which drug route of administration would they choose. RESULTS: One hundred and twenty-five patients fulfilled the inclusion criteria and were issued questionnaires, of these 78 questionnaires were returned (62 percent response). The mean age of respondent was 44 years. Of the total number of respondents, 33 patients (42 percent) preferred infliximab and 19 patients (24 percent) preferred adalimumab (p = 0.07). Twenty-six patients (33 percent) did not indicate a preference for either biological therapy and were not included in the final analysis. The commonest reason cited for those who chose infliximab (iv) was: "I do not like the idea of self-injecting," (67 percent). For those patients who preferred adalimumab (sc) the commonest reason cited was: "I prefer the convenience of injecting at home," (79 percent). Of those patients who had previously been treated with an anti-TNF therapy (n = 10, all infliximab) six patients stated that they would prefer infliximab if given the choice

  6. Physico-chemical stability of eribulin mesylate containing concentrate and ready-to-administer solutions.

    Science.gov (United States)

    Spindeldreier, Kirsten; Thiesen, Judith; Lipp, Hans-Peter; Krämer, Irene

    2014-06-01

    The aim of this study was to determine the stability of commercially available eribulin mesylate containing injection solution as well as diluted ready-to-administer solutions stored under refrigeration or at room temperature. Stability was studied by a novel developed stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) assay with ultraviolet detection (detection wavelength 200 nm). Triplicate test solutions of eribulin mesylate containing injection concentrate (0.5 mg/mL) and with 0.9% sodium chloride solution diluted ready-to-administer preparations (0.205 mg/mL eribulin mesylate in polypropylene (PP) syringes, 0.020 mg/mL eribulin mesylate in polypropylene/polyethylene (PE) bags) were stored protected from light either at room temperature (25) or under refrigeration (2-8). Samples were withdrawn on day 0 (initial), 1, 3, 5, 7, 14, 21 and 28 of storage and assayed. Physical stability was determined by measuring the pH value once a week and checking for visible precipitations or colour changes. The stability tests revealed that concentrations of eribulin mesylate remained unchanged over a period of 28 days irrespective of concentration, container material or storage temperature. Neither colour changes nor visible particles have been observed. The pH value varied slightly over time but remained in the stability favourable range of 5-9. Eribulin mesylate injection (0.5 mg/mL) is physico-chemically stable over a period of 28 days after first puncture of the vial. After dilution with 0.9% NaCl vehicle solution, ready-to-administer eribulin mesylate injection solutions (0.205 mg/mL in PP syringe) and infusion solutions (0.02 mg/mL in prefilled PP/PE bags) are physico-chemically stable for a period of at least four weeks either refrigerated or stored at room temperature. For microbiological reasons storage under refrigeration is recommended.

  7. Radiation exposure to nuclear medicine technologists from administering I-131 therapy dosages

    International Nuclear Information System (INIS)

    Chaudakshetrin, P.; Pusuwan, P.; Sritongkul, N.; Tuntawiroon, M.

    2007-01-01

    Full text: Therapeutic doses of I-131 for treatment of thyroid cancer are administered orally in liquid or capsule form. During the last few years, a total number of patients loaded in our isolation ward increased from 4 to 10 patients per week. When considering radiation safety precautions for attending technologists, it is preferable to use the dose in capsules. The purpose of this study is to compare radiation exposure to nuclear medicine technologists from administering I-131 therapy dosages in capsules and in liquid form in a closed system. Materials and Methods: Three year radiation exposure to technologists during I-131 administration was analyzed. From January 2004 to June 2005 dose administration was in liquid form (n=263) and from July 2005 to February 2007 in capsules (n=541). Radiation dose assessment was performed with an electronic personal dosimeter (PDM 112). The dose rate in μSv and time spent per patient were recorded. Results: Dose received per patient when I-131 was given in a liquid was 3.50 ± 1.67 μSv and 1.17 ± 0.66 μSv when given in capsules. Compared with the use of a liquid, capsules significantly reduced radiation dose to technologists by 66% (P < 0.001). These doses received depended not only on the administered activity but also on the time, distance and shielding. Time spent per patient, including a brief visit before the time of dosing to explain the procedure and answer questions was reduced slightly from 4.4 ± 2.2 to 3.7 ± 1.8 minutes (P < 0.01). These correspond to a reduction in a yearly dose to 1 technologist by 40%, from 0.63 mSv to 0.38 mSv from dosing to 175 and 325 patients respectively. Conclusions: The measured doses clearly showed that handling of I-131 therapy dosages either in a liquid form or capsules are not the major contributors to the technologist's radiation exposure in routine clinical practice. However, one has to be cautious and follow good work practice to avoid risk of radiation exposure and radioiodine

  8. How do patients with inflammatory bowel disease want their biological therapy administered?

    Directory of Open Access Journals (Sweden)

    Lindsay Hannah

    2010-01-01

    Full Text Available Abstract Background Infliximab is usually administered by two monthly intravenous (iv infusions, therefore requiring visits to hospital. Adalimumab is administered by self subcutaneous (sc injections every other week. Both of these anti-TNF drugs appear to be equally efficacious in the treatment of Crohn's Disease and therefore the decision regarding which drug to choose will depend to some extent on patient choice, which may be based on the mode of administration. The aims of this study were to compare preferences in Inflammatory Bowel Disease (IBD patients for two currently available anti-TNF agents and the reasons for their choices. Methods An anonymous questionnaire was distributed to IBD patients who had attended the Gastroenterology service (Ulster Hospital, Dundonald, Belfast, N. Ireland. UK between January 2007 and December 2007. The patients were asked in a hypothetical situation if the following administering methods of anti-TNF drugs (intravenous or subcutaneous were available, which drug route of administration would they choose. Results One hundred and twenty-five patients fulfilled the inclusion criteria and were issued questionnaires, of these 78 questionnaires were returned (62 percent response. The mean age of respondent was 44 years. Of the total number of respondents, 33 patients (42 percent preferred infliximab and 19 patients (24 percent preferred adalimumab (p = 0.07. Twenty-six patients (33 percent did not indicate a preference for either biological therapy and were not included in the final analysis. The commonest reason cited for those who chose infliximab (iv was: "I do not like the idea of self-injecting," (67 percent. For those patients who preferred adalimumab (sc the commonest reason cited was: "I prefer the convenience of injecting at home," (79 percent. Of those patients who had previously been treated with an anti-TNF therapy (n = 10, all infliximab six patients stated that they would prefer infliximab if given

  9. Lay health worker experiences administering a multi-level combination intervention to improve PMTCT retention.

    Science.gov (United States)

    DiCarlo, Abby; Fayorsey, Ruby; Syengo, Masila; Chege, Duncan; Sirengo, Martin; Reidy, William; Otieno, Juliana; Omoto, Jackton; Hawken, Mark P; Abrams, Elaine J

    2018-01-10

    The recent scale-up of prevention of mother-to-child transmission of HIV (PMTCT) services has rapidly accelerated antiretroviral therapy (ART) uptake among pregnant and postpartum women in sub-Saharan Africa. The Mother and Infant Retention for Health (MIR4Health) study evaluates the impact of a combination intervention administered by trained lay health workers to decrease attrition among HIV-positive women initiating PMTCT services and their infants through 6 months postpartum. This was a qualitative study nested within the MIR4Health trial. MIR4Health was conducted at 10 health facilities in Nyanza, Kenya from September 2013 to September 2015. The trial intervention addressed behavioral, social, and structural barriers to PMTCT retention and included: appointment reminders via text and phone calls, follow-up and tracking for missed clinic visits, PMTCT health education at home visits and during clinic visits, and retention and adherence support and counseling. All interventions were administered by lay health workers. We describe results of a nested small qualitative inquiry which conducted two focus groups to assess the experiences and perceptions of lay health workers administering the interventions. Discussions were recorded and simultaneously transcribed and translated into English. Data were analyzed using framework analysis approach. Study findings show lay health workers played a critical role supporting mothers in PMTCT services across a range of behavioral, social, and structural domains, including improved communication and contact, health education, peer support, and patient advocacy and assistance. Findings also identified barriers to the uptake and implementation of the interventions, such as concerns about privacy and stigma, and the limitations of the healthcare system including healthcare worker attitudes. Overall, study findings indicate that lay health workers found the interventions to be feasible, acceptable, and well received by clients. Lay

  10. A systematic review and meta-analysis of written self-administered psychosocial interventions among adults with a physical illness.

    Science.gov (United States)

    Lambert, Sylvie D; Beatty, Lisa; McElduff, Patrick; Levesque, Janelle V; Lawsin, Catalina; Jacobsen, Paul; Turner, Jane; Girgis, Afaf

    2017-12-01

    The cost of implementing professionally-led psychosocial interventions has limited their integration into routine care. To enhance the translation of effective psychosocial interventions in routine care, a self-administered format is sometimes used. The meta-analysis examined the efficacy of written self-administered, psychosocial interventions to improve outcomes among individuals with a physical illness. Studies comparing a written self-administered intervention to a control group were identified through electronic databases searching. Pooled effect sizes were calculated across follow-up time points using random-effects models. Studies were also categorised according to three levels of guidance (self-administered, minimal contact, or guided) to examine the effect of this variable on outcomes. Forty manuscripts were retained for the descriptive review and 28 for the meta-analysis. Findings were significant for anxiety, depression, distress, and self-efficacy. Results were not significant for quality of life and related domains as well as coping. Purely self-administered interventions were efficacious for depression, distress, and self-efficacy; only guided interventions had an impact on anxiety. Findings showed that written self-administered interventions show promise across a number of outcomes. Self-administered interventions are a potentially efficacious and cost-effective approach to address some of the most common needs of patients with a physical illness. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. National Systematic Legal Review of State Policies on Emergency Medical Services Licensure Levels' Authority to Administer Opioid Antagonists.

    Science.gov (United States)

    Kinsman, Jeremiah M; Robinson, Kathy

    2018-02-27

    Previous research conducted in November 2013 found there were a limited number of states and territories in the United States (US) that authorize emergency medical technicians (EMTs) and emergency medical responders (EMRs) to administer opioid antagonists. Given the continued increase in the number of opioid-related overdoses and deaths, many states have changed their policies to authorize EMTs and EMRs to administer opioid antagonists. The goal of this study is to provide an updated description of policy on EMS licensure levels' authority to administer opioid antagonists for all 50 US states, the District of Columbia (DC), and the Commonwealth of Puerto Rico (PR). State law and scopes of practice were systematically reviewed using a multi-tiered approach to determine each state's legally-defined EMS licensure levels and their authority to administer an opioid antagonist. State law, state EMS websites, and state EMS scope of practice documents were identified and searched using Google Advanced Search with Boolean Search Strings. Initial results of the review were sent to each state office of EMS for review and comment. As of September 1, 2017, 49 states and DC authorize EMTs to administer an opioid antagonist. Among the 40 US jurisdictions (39 states and DC) that define the EMR or a comparable first responder licensure level in state law, 37 states and DC authorize their EMRs to administer an opioid antagonist. Paramedics are authorized to administer opioid antagonists in all 50 states, DC, and PR. All 49 of the US jurisdictions (48 states and DC) that define the advanced emergency medical technician (AEMT) or a comparable intermediate EMS licensure level in state law authorize their AEMTs to administer an opioid antagonist. 49 out of 52 US jurisdictions (50 states, DC, and PR) authorize all existing levels of EMS licensure levels to administer an opioid antagonist. Expanding access to this medication can save lives, especially in communities that have limited

  12. A phase I clinical study to evaluate safety of orally administered, genetically engineered Salmonella enterica serovar Typhimurium for canine osteosarcoma

    OpenAIRE

    Fritz, Sara; Henson, Michael; Greengard, Emily; Winter, Amber; Stuebner, Kathleen; Yoon, Una; Wilk, Vicki; Borgatti, Antonella; Augustin, Lance; Modiano, Jaime; Saltzman, Daniel

    2017-01-01

    Abstract We conducted a prospective phase I study to evaluate safety of an orally administered Salmonella encoding IL‐2 (SalpIL2) in combination with amputation and adjuvant doxorubicin for canine appendicular osteosarcoma. Efficacy was assessed as a secondary measure. The first dose of SalpIL2 was administered to 19 dogs on Day 0; amputation was done after 10 days with chemotherapy following 2 weeks later. SalpIL2 was administered concurrent with chemotherapy, for a total of five doses of do...

  13. Calculation of radiation exposures from patients to whom radioactive materials have been administered

    Science.gov (United States)

    Cormack, John; Shearer, Jane

    1998-03-01

    Spreadsheet templates which calculate cumulative exposures to other persons from patients to whom radioactive materials have been administered have been developed by the authors. Calculations can be based on any specified single-, bi- or tri-exponential whole-body clearance rate and a diurnal (or any other periodic) contact pattern. The time (post-administration) during which close contact should be avoided in order to constrain the radiation exposure and exposure rates to selected limits is also calculated using an iterative technique (Newton's method), and the residual activity at the time when contact can resume is also calculated. These templates find particular application in the calculation of exposures to persons who are in contact with patients who have received for therapeutic purposes. The effect of changing dose limits, contact patterns and using individually derived clearance rates may be readily modelled.

  14. How Medicaid agencies administer mental health services: results from a 50-state survey.

    Science.gov (United States)

    Verdier, James; Barrett, Allison

    2008-10-01

    This brief report describes some notable variations in how state Medicaid agencies administer and fund Medicaid mental health services. Hour-long telephone interviews were conducted with all state and District of Columbia Medicaid directors or their designees. Responses indicated that Medicaid and mental health agencies were located within the same umbrella agency in 28 states, potentially facilitating collaboration. The mental health agency provided funding for some Medicaid mental health services in 32 states, and counties provided such funding in 22 states. Medicaid agencies generally delegated more authority to state mental health agencies in states where some Medicaid funding came from mental health sources and also in states where both agencies were in the same umbrella agency. The increasing role of Medicaid in funding state mental health services, combined with new federal limits on Medicaid financing of these services, underscores the importance of interagency collaboration and better alignment of Medicaid and mental health responsibilities.

  15. Administered activity optimization of the MDP labeled with Tc-99 m in bone tip studies

    International Nuclear Information System (INIS)

    Perez Diaz, Marlen; Esteves Aparicio, Eric; Dopico Hernandez, Rolando; Gorrin, Orlando Cabrera

    2003-01-01

    The aim of the present study was to determine the optimum activity of the Cuban MDP labeled with Tc-99 m, for establishing a compromise relation between image quality and patient radiological protection in Nuclear Medicine studies. The used statistical technique was the discriminant analysis to arrive at the optimization criterion. Three samples of 18 patients each were selected. Each sample was undergone to a different acquisition protocol. Each sample was divided into three groups of 6 patients each. The administered activities were: 293 MBq, 430 MBq or 598 MBq. Images of hands and femurs were graded for each study. The ratios Signal /Background and Signal/ Noise were processed. The value of 430 MBq was enough to obtain good image quality using a protocol of 10 minutes of acquisition for the used technical conditions. (author)

  16. Lack of postoperative pain relief after hysterectomy using preperitoneally administered bupivacaine

    DEFF Research Database (Denmark)

    Kristensen, Billy Bjarne; Christensen, D S; Østergaard, Mette

    1999-01-01

    the subcutaneous, layer. The present study investigated the effect of frequent bolus injections of bupivacaine (15 mL 2.5 mg/mL) preperitoneally through catheters placed intraoperatively in women who had undergone hysterectomy. METHODS: Postoperative pain and analgesic requirements were studied in a double...... bupivacaine (15 mL 2.5 mg/mL) every 4 hours for 48 hours via each catheter starting in the operating room. The placebo group (n = 19) received saline in a like manner. Postoperative pain was evaluated using a visual analog scale (VAS) and verbal rating scale (VRS) twice a day for 2 days at rest...... and on movement. Requirements of supplementary analgesics were monitored, as was wound infection after discharge. RESULTS: Bupivacaine administered preperitoneally did not improve analgesia at rest, during coughing, or during mobilization compared with saline. No difference between the groups was found regarding...

  17. Dose and elasticity of demand for self-administered cocaine in rats.

    Science.gov (United States)

    Kearns, David N; Silberberg, Alan

    2016-04-01

    The present experiment tested whether the elasticity of demand for self-administered cocaine in rats is dose-dependent. Subjects lever pressed for three different doses of intravenous cocaine - 0.11, 0.33, and 1.0 mg/kg/infusion - on a demand procedure where the number of lever presses required per infusion increased within a session. The main finding was that demand for the 0.11 mg/kg dose was more elastic than it was for the two larger doses. There was no difference in demand elasticity between the 0.33 and 1.0 mg/kg doses. These results parallel findings previously reported in monkeys. The present study also demonstrated that a within-session procedure can be used to generate reliable demand curves.

  18. Correlation of administered activity and dosimetric data in patients treated with 131MIBG therapy

    International Nuclear Information System (INIS)

    Castellani, M.; Chiesa, C.; Aliberti, G.; Maccauro, M.; Seregni, E.; Lorenzoni, A.; Luksch, R.

    2015-01-01

    Full text of publication follows. Aims: the purpose of the study was to optimized 131-MIBG (or 131 I-MIBG) therapy in children and adults patients with neural crest tumors, by correlating the administered pro/KXg activity to whole-body dosimetry and hematologic toxicity. Materials and methods: from September 2003, to June 2012 twenty-four patients (9 children, 15 adults) (13 neuroblastoma, 9 pheochromocytoma/paraganglioma, 2 medullary thyroid carcinoma) treated with 131 I-MIBG were enrolled in the study. In each patient dosimetric estimation was carried out with MIRD method after patient therapy, using imaging acquisition or probe determination (from 1 to 168 hours). Hematological toxicity was evaluated according to WHO grade by weekly blood count for at least 6 weeks or until recovery. Whole Body Dose (WBD) was correlated with administered pro/KXg activity and bone marrow toxicity. Results: a total of forty-five dosimetric studies have been performed, 16/45 in children and 29/45 in adult patients. Administered activity ranged from 7.4 to 16.65 GBq, corresponding in children to 5-21 mCi/KXg (median 10 mCi/KXg) and in adults to 3-7 mCi/KXg. (median 5 mCi/KXg). In 4 patients (3 children, 1 adult) 2 weeks after 131 I-MING therapy autologous stem cell transplantations were performed. Grade II-III hematological toxicity was observed in all children and in 6/15 adult patient. Whole Body Dose ranged from 1 Gy to 3.6 Gy (median 1.7 Gy) in children, meanwhile it ranged between 0.55 and 1.87 Gy (median 0.96 Gy) in adults. In 5/16 children studies WBD was about 2 Gy and one child received a dose of 3.6 Gy (0.4 Gy/GBq), corresponding to an activity of 18 mCi/KXg. Conclusion: contrary to published data in children the pro/KXg activity is not a good predictor of WBD. In these cases WBD calculation can be affected by the presence of large tumor masses which overestimates the absorbed dose. In any case the administration of activity superior to 15 mCi/KXg is known to be associated

  19. Prophylactic efficacy of lithium administered every second day: a WHO multicentre study

    DEFF Research Database (Denmark)

    Plenge, P; Amin, M; Agarwal, A K

    1999-01-01

    OBJECTIVES: To study the prophylactic efficacy of lithium administered every second day to patients with bipolar disorder or recurrent unipolar depressive disorder. METHODS: The study was carried out as a WHO multicentre study in five different psychiatric clinics: Russia (Moscow), Canada (Montreal......), India (Lucknow), Germany (Munich) and South Korea (Pusan), with the lithium tablets being supplied from Denmark (Copenhagen). Participation in the study was conditional on the patient having been in prophylactic lithium treatment for the preceding 2-year period and having been free of depressive...... of bipolar disorder and five with a diagnosis of recurrent unipolar depressive disorder, participated in the study. The number of patients from each centre ranged from six to 11. The mean lithium dose every second day was 36 mmol lithium, leading to a mean 12-h standard serum lithium concentration during...

  20. The role of capnography in endoscopy patients undergoing nurse-administered propofol sedation

    DEFF Research Database (Denmark)

    Slagelse, Charlotte; Vilmann, Peter; Hornslet, Pernille

    2013-01-01

    . The existing literature on capnography for endoscopy patients sedated with nurse-administered propofol sedation (NAPS) is limited. Can the addition of capnography to standard monitoring during endoscopy with NAPS reduce the number, duration, and level of hypoxia. Materials and methods. This study...... capnography, were included in the analysis. The number and total duration of hypoxia was reduced by 39.3% and 21.1% in the intervention group compared to the control group (p > 0.05). No differences in actions taken against insufficient respiration were found. Changes in end-tidal carbon dioxide (R = 0.177, p......-value 0.05). Capnography is able to detect insufficient respiration that may lead to hypoxia prior to changes in pulse oximetry. However, due to a limited clinical benefit and additional costs associated with capnography, we do not find capnography necessary during the use of NAPS....

  1. High efficacy with deep nurse-administered propofol sedation for advanced gastroenterologic endoscopic procedures

    DEFF Research Database (Denmark)

    Jensen, Jeppe Thue; Hornslet, Pernille; Konge, Lars

    2016-01-01

    was requested eight times (0.4 %). One patient was intubated due to suspected aspiration. CONCLUSIONS: Intermittent deep NAPS for advanced endoscopies in selected patients provided an almost 100 % success rate. However, the rate of hypoxia, hypotension and respiratory support was high compared with previously......BACKGROUND AND STUDY AIMS: Whereas data on moderate nurse-administered propofol sedation (NAPS) efficacy and safety for standard endoscopy is abundant, few reports on the use of deep sedation by endoscopy nurses during advanced endoscopy, such as Endoscopic Retrograde Cholangiopancreatography (ERCP......) and Endoscopic Ultrasound (EUS) are available and potential benefits or hazards remain unclear. The aims of this study were to investigate the efficacy of intermittent deep sedation with propofol for a large cohort of advanced endoscopies and to provide data on the safety. PATIENTS AND METHODS: All available...

  2. Calculation of radiation exposures from patients to whom radioactive materials have been administered

    International Nuclear Information System (INIS)

    McCormack, J.; Shearer, J.

    1998-01-01

    Spreadsheet templates have been developed by the authors to calculate radiation exposures to others from patients to whom radioactive materials have been administered (or, indeed, from any source of radiation exposure) to be readily calculated. The time during which contact should be avoided, along with the residual activity at resumption of contact is also calculated using an iterative technique. These spreadsheets allow a great deal of flexibility in the specification of clearance rates and close contact patterns for individual patients. Estimates of doses, restriction times and residual activities for 131 l thyrotoxic therapy, for various contact patterns and group of patients, were calculated. The spreadsheets are implemented using Microsoft EXCEL for both PC and Macintosh computers, and are readily available from the authors

  3. Fractionation of radioactivity in the milk of goats administered 14C-aflatoxin B1

    International Nuclear Information System (INIS)

    Goto, T.; Hsieh, D.P.

    1985-01-01

    A detailed fractionation of radioactivity in the milk of goats administered 14 C-aflatoxin B1 at low doses was performed. The milk collected in the first 24 h following dosing contained radioactivity equivalent to 0.45-1.1% of the dose given. The radioactivity in each sample was partitioned into 4 fractions: ether, protein, dichloromethane, and water-alcohol. Over 80% of the radioactivity was detected in the dichloromethane fraction, of which over 95% was attributable to aflatoxin M1. No aflatoxin B1 or other known aflatoxin metabolites were detected in any fraction. The results indicate that the major metabolite of aflatoxin B1 in goat milk is aflatoxin M1 and that other metabolites, including conjugates, are of minor significance

  4. Analgesic and cardiopulmonary effects of intrathecally administered romifidine or romifidine and ketamine in goats (Capra hircus

    Directory of Open Access Journals (Sweden)

    H.P. Aithal

    2001-07-01

    Full Text Available The study was conducted to evaluate the effects of romifidine alone (50 µg/kg and a combination of romifidine (50 µg/kg and ketamine (2.5 mg/kg after intrathecal administration in goats. Ten adult goats of either sex weighing between 15 and 20 kg were randomly placed in 2 groups (groups I and II. The agents were administered at the lumbosacral subarachnoid space. Clinico-physiological parameters such as analgesia, motor incoordination, sedation, salivation, heart rate, respiratory rate, arterial pressure, central venous pressure and rectal temperature were studied. Other haematobiochemical parameters monitored were packed cell volume, haemoglobin, plasma proteins, glucose, urea and creatinine. The onset of analgesia was faster in group II (35.5 ±6.25 s compared to that of group I (5.2 ±0.54 min. Analgesia of the tail, perineum, hind limbs, flank and thorax was mild to moderate in group I, but complete analgesia of tail, perineum and hind limbs was recorded in group II. Motor incoordination was mild in group I and severe in group II. Significant reduction in heart rate (more pronounced in group I and respiratory rate (more pronounced in group II, and a significant increase in central venous pressure were recorded in both groups. Mean arterial pressure was reduced in both groups, but more markedly in group I. Sedation, electro-cardiogram, rectal temperature and haemato-biochemical parameters did not show significant differences between the 2 groups. The results of this study indicated a possible synergistic analgesic interaction between intrathecally administered romifidine and ketamine, without causing any marked systemic effects in goats.

  5. Regulatory analysis on criteria for the release of patients administered radioactive material

    International Nuclear Information System (INIS)

    Schneider, S.; McGuire, S.A.

    1994-05-01

    The Nuclear Regulatory Commission (NRC) has received two petitions to amend its regulations in 10 CFR Parts 20 and 35 as they apply to doses received by members of the public exposed to patients released from a hospital after they have been administered radioactive material. While the two petitions are not identical they both request that the NRC establish a dose limit of 5 millisieverts (0.5 rem) per year for individuals exposed to patients who have been administered radioactive materials. This Regulatory Analysis evaluates three alternatives. Alternative 1 is for the NRC to amend its patient release criteria in 10 CFR 35.75 to use the more stringent dose limit of 1 millisievert per year in 10 CFR 20.1301(a) for its patient release criteria. Alternative 2 is for the NRC to continue using the existing patient release criteria in 10 CFR 35.75 of 1,110 megabecquerels of activity or a dose rate at one meter from the patient of 0.05 millisievert per hour. Alternative 3 is for the NRC to amend the patient release criteria in 10 CFR 35.75 to specify a dose limit of 5 millisieverts for patient release. The evaluation indicates that Alternative 1 would cause a prohibitively large increase in the national health care cost from retaining patients in a hospital longer and would cause significant personal and psychological costs to patients and their families. The choice of Alternatives 2 or 3 would affect only thyroid cancer patients treated with iodine-131. For those patients, Alternative 3 would result in less hospitalization than Alternative 2. Alternative 3 has a potential decrease in national health care cost of $30,000,000 per year but would increase the potential collective dose from released therapy patients by about 2,700 person-rem per year, mainly to family members

  6. Effects of urine alkalization and activated charcoal on the pharmacokinetics of orally administered carprofen in dogs.

    Science.gov (United States)

    Raekallio, Marja R; Honkavaara, Juhana M; Säkkinen, Mia S; Peltoniemi, S Marikki

    2007-04-01

    To investigate the effects of oral administration of activated charcoal (AC) and urine alkalinization via oral administration of sodium bicarbonate on the pharmacokinetics of orally administered carprofen in dogs. 6 neutered male Beagles. Each dog underwent 3 experiments (6-week interval between experiments). The dogs received a single dose of carprofen (16 mg/kg) orally at the beginning of each experiment; after 30 minutes, sodium bicarbonate (40 mg/kg, PO), AC solution (2.5 g/kg, PO), or no other treatments were administered. Plasma concentrations of unchanged carprofen were determined via high-performance liquid chromatography at intervals until 48 hours after carprofen administration. Data were analyzed by use of a Student paired t test or Wilcoxon matched-pairs rank test. Compared with the control treatment, administration of AC decreased plasma carprofen concentrations (mean +/- SD maximum concentration was 85.9 +/- 11.9 mg/L and 58.1 +/- 17.6 mg/L, and area under the time-concentration curve was 960 +/- 233 mg/L x h and 373 +/- 133 mg/L x h after control and AC treatment, respectively). The elimination half-life remained constant. Administration of sodium bicarbonate had no effect on plasma drug concentrations. After oral administration of carprofen in dogs, administration of AC effectively decreased maximum plasma carprofen concentration, compared with the control treatment, probably by decreasing carprofen absorption. Results suggest that AC can be used to reduce systemic carprofen absorption in dogs receiving an overdose of carprofen. Oral administration of 1 dose of sodium bicarbonate had no apparent impact on carprofen kinetics in dogs.

  7. Regulatory analysis on criteria for the release of patients administered radioactive material

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, S.; McGuire, S.A. [Nuclear Regulatory Commission, Washington, DC (United States). Div. of Regulatory Applications; Behling, U.H.; Behling, K.; Goldin, D. [Cohen (S.) and Associates, Inc., McLean, VA (United States)

    1994-05-01

    The Nuclear Regulatory Commission (NRC) has received two petitions to amend its regulations in 10 CFR Parts 20 and 35 as they apply to doses received by members of the public exposed to patients released from a hospital after they have been administered radioactive material. While the two petitions are not identical they both request that the NRC establish a dose limit of 5 millisieverts (0.5 rem) per year for individuals exposed to patients who have been administered radioactive materials. This Regulatory Analysis evaluates three alternatives. Alternative 1 is for the NRC to amend its patient release criteria in 10 CFR 35.75 to use the more stringent dose limit of 1 millisievert per year in 10 CFR 20.1301(a) for its patient release criteria. Alternative 2 is for the NRC to continue using the existing patient release criteria in 10 CFR 35.75 of 1,110 megabecquerels of activity or a dose rate at one meter from the patient of 0.05 millisievert per hour. Alternative 3 is for the NRC to amend the patient release criteria in 10 CFR 35.75 to specify a dose limit of 5 millisieverts for patient release. The evaluation indicates that Alternative 1 would cause a prohibitively large increase in the national health care cost from retaining patients in a hospital longer and would cause significant personal and psychological costs to patients and their families. The choice of Alternatives 2 or 3 would affect only thyroid cancer patients treated with iodine-131. For those patients, Alternative 3 would result in less hospitalization than Alternative 2. Alternative 3 has a potential decrease in national health care cost of $30,000,000 per year but would increase the potential collective dose from released therapy patients by about 2,700 person-rem per year, mainly to family members.

  8. Personal hygiene among military personnel: developing and testing a self-administered scale.

    Science.gov (United States)

    Saffari, Mohsen; Koenig, Harold G; Pakpour, Amir H; Sanaeinasab, Hormoz; Jahan, Hojat Rshidi; Sehlo, Mohammad Gamal

    2014-03-01

    Good personal hygiene (PH) behavior is recommended to prevent contagious diseases, and members of military forces may be at high risk for contracting contagious diseases. The aim of this study was to develop and test a new questionnaire on PH for soldiers. Participants were all male and from different military settings throughout Iran. Using a five-stage guideline, a panel of experts in the Persian language (Farsi) developed a 21-item self-administered questionnaire. Face and content validity of the first-draft items were assessed. The questionnaire was then translated and subsequently back-translated into English, and both the Farsi and English versions were tested in pilot studies. The consistency and stability of the questionnaire were tested using Cronbach's alpha and the test-retest strategy. The final scale was administered to a sample of 502 military personnel. Explanatory and confirmatory factor analyses evaluated the structure of the scale. Both the convergent and discriminative validity of the scale were also determined. Cronbach's alpha coefficients were >0.85. Principal component analysis demonstrated a uni-dimensional structure that explained 59 % of the variance in PH behaviors. Confirmatory factor analysis indicated a good fit (goodness-of-fit index = 0.902; comparative fitness index = 0.923; root mean square error of approximation = 0.0085). The results show that this new PH scale has solid psychometric properties for testing PH behaviors among an Iranian sample of military personnel. We conclude that this scale can be a useful tool for assessing PH behaviors in military personnel. Further research is needed to determine the scale's value in other countries and cultures.

  9. The COX-2 inhibitor meloxicam prevents pregnancy when administered as an emergency contraceptive to nonhuman primates.

    Science.gov (United States)

    McCann, Nicole C; Lynch, Terrie J; Kim, Soon Ok; Duffy, Diane M

    2013-12-01

    Cyclooxygenase-2 (COX-2) inhibitors reduce prostaglandin synthesis and disrupt essential reproductive processes. Ultrasound studies in women demonstrated that oral COX-2 inhibitors can delay or prevent follicle collapse associated with ovulation. The goal of this study was to determine if oral administration of a COX-2 inhibitor can inhibit reproductive function with sufficient efficacy to prevent pregnancy in primates. The COX-2 inhibitor meloxicam (or vehicle) was administered orally to proven fertile female cynomolgus macaques using one emergency contraceptive model and three monthly contraceptive models. In the emergency contraceptive model, females were bred with a proven fertile male once 2±1 days before ovulation, returned to the females' home cage, and then received 5 days of meloxicam treatment. In the monthly contraceptive models, females were co-caged for breeding with a proven fertile male for a total of 5 days beginning 2±1 days before ovulation. Animals received meloxicam treatment (1) cycle days 5-22, or (2) every day, or (3) each day of the 5-day breeding period. Female were then assessed for pregnancy. The pregnancy rate with meloxicam administration using the emergency contraception model was 6.5%, significantly lower than the pregnancy rate of 33.3% when vehicle without meloxicam was administered. Pregnancy rates with the three monthly contraceptive models (75%-100%) were not consistent with preventing pregnancy. Oral COX-2 inhibitor administration can prevent pregnancy after a single instance of breeding in primates. While meloxicam may be ineffective for regular contraception, pharmacological inhibition of COX-2 may be an effective method of emergency contraception for women. COX-2 inhibitors can interfere with ovulation, but the contraceptive efficacy of drugs of this class has not been directly tested. This study, conducted in nonhuman primates, is the first to suggest that a COX-2 inhibitor may be effective as an emergency contraceptive.

  10. Costs of outpatient parenteral antimicrobial therapy (OPAT) administered by Hospital at Home units in Spain.

    Science.gov (United States)

    González-Ramallo, V J; Mirón-Rubio, M; Mujal, A; Estrada, O; Forné, C; Aragón, B; Rivera, A J

    2017-07-01

    The aim of this study was to assess the direct healthcare costs of outpatient parenteral antimicrobial therapy (OPAT) administered by Hospital at Home (HaH) units in Spain. An observational, multicentre, economic evaluation of retrospective cohorts was conducted. Patients were treated at home by the HaH units of three Spanish hospitals between January 2012 and December 2013. From the cost accounting of HaH OPAT (staff, pharmacy, transportation, diagnostic tests and structural), the cost of each outpatient course was obtained following a top-down strategy based on the use of resources. Costs associated with inpatient stay, if any, were estimated based on length of stay and ICD-9-CM diagnosis. There were 1324 HaH episodes in 1190 patients (median age 70 years). The median (interquartile range) stay at home was 10 days (7-15 days). Of the OPAT episodes, 91.5% resulted in cure or improvement on completion of intravenous therapy. The mean total cost of each infectious episode was €6707 [95% confidence interval (CI) €6189-7406]. The mean cost per OPAT episode was €1356 (95% CI €1247-1560), mainly distributed between healthcare staff costs (46%) and pharmacy costs (39%). The mean cost of inpatient hospitalisation of an infectious episode was €4357 (95% CI €3947-4977). The cost per day of inpatient hospitalisation was €519, whilst the cost per day of OPAT was €98, meaning a saving of 81%. This study shows that OPAT administered by HaH units resulted in lower costs compared with inpatient care in Spain. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  11. Immunobiotic Lactobacillus administered post-exposure averts the lethal sequelae of respiratory virus infection.

    Science.gov (United States)

    Percopo, Caroline M; Rice, Tyler A; Brenner, Todd A; Dyer, Kimberly D; Luo, Janice L; Kanakabandi, Kishore; Sturdevant, Daniel E; Porcella, Stephen F; Domachowske, Joseph B; Keicher, Jesse D; Rosenberg, Helene F

    2015-09-01

    We reported previously that priming of the respiratory tract with immunobiotic Lactobacillus prior to virus challenge protects mice against subsequent lethal infection with pneumonia virus of mice (PVM). We present here the results of gene microarray which document differential expression of proinflammatory mediators in response to PVM infection alone and those suppressed in response to Lactobacillus plantarum. We also demonstrate for the first time that intranasal inoculation with live or heat-inactivated L. plantarum or Lactobacillus reuteri promotes full survival from PVM infection when administered within 24h after virus challenge. Survival in response to L. plantarum administered after virus challenge is associated with suppression of proinflammatory cytokines, limited virus recovery, and diminished neutrophil recruitment to lung tissue and airways. Utilizing this post-virus challenge protocol, we found that protective responses elicited by L. plantarum at the respiratory tract were distinct from those at the gastrointestinal mucosa, as mice devoid of the anti-inflammatory cytokine, interleukin (IL)-10, exhibit survival and inflammatory responses that are indistinguishable from those of their wild-type counterparts. Finally, although L. plantarum interacts specifically with pattern recognition receptors TLR2 and NOD2, the respective gene-deleted mice were fully protected against lethal PVM infection by L. plantarum, as are mice devoid of type I interferon receptors. Taken together, L. plantarum is a versatile and flexible agent that is capable of averting the lethal sequelae of severe respiratory infection both prior to and post-virus challenge via complex and potentially redundant mechanisms. Published by Elsevier B.V.

  12. Adequate plasma drug concentrations suggest that amoxicillin can be administered by continuous infusion using elastomeric pumps.

    Science.gov (United States)

    Arensdorff, Lyne; Boillat-Blanco, Noémie; Decosterd, Laurent; Buclin, Thierry; de Vallière, Serge

    2017-09-01

    Elastomeric pumps can be useful for the administration of antibiotics in the outpatient setting. To determine amoxicillin degradation in elastomeric pumps, as well as the effectiveness of amoxicillin treatment administered by elastomeric pumps. Antibiotic degradation was measured in elastomeric pumps filled with 6 g of amoxicillin in 240 mL of NaCl 0.9% by drawing samples at 12 h intervals when stored in the fridge for 48 h and when worn around the waist for 24 h. Subsequently nine patients were treated with continuous infusions of 8 or 12 g of amoxicillin per day. Plasma amoxicillin concentrations were measured on each visit to the outpatient parenteral antibiotic therapy unit. Clinical outcome was verified 3 months after the end of treatment. Amoxicillin degradation in elastomeric pumps reached 10% after 48 h in the fridge and an additional 30% when worn around the waist for 24 h. Mean plasma drug concentrations achieved with 12 g of amoxicillin per day were 18.5 mg/L (95% CI 13.5-23.5), which is largely above the MIC of amoxicillin-susceptible bacteria. Nine patients treated for various complicated infections were cured and had no unexpected adverse effects. Adequate plasma drug concentrations and favourable clinical outcomes suggest that amoxicillin can be administered by continuous infusion using elastomeric pumps. This treatment modality does not fulfil formal requirements regarding pharmaceutical stability, but the resulting safety impact in patients is probably limited. Therapeutic drug monitoring and a close clinical follow-up are recommended if this route of administration is chosen. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Identification of drug combinations administered by continuous subcutaneous infusion that require analysis for compatibility and stability.

    Science.gov (United States)

    Dickman, Andrew; Bickerstaff, Matthew; Jackson, Richard; Schneider, Jennifer; Mason, Stephen; Ellershaw, John

    2017-03-23

    A continuous subcutaneous infusion (CSCI) delivered via syringe pump is a method of drug administration used to maintain symptom control when a patient is no longer able to tolerate oral medication. Several classes of drugs, such as opioids, antiemetics, anticholinergics, antipsychotics and benzodiazepines are routinely administered by CSCI alone or in combinations. Previous studies attempting to identify the most-common CSCI combinations are now several years old and no longer reflect current clinical practice. The aim of this work was to review current clinical practice and identify CSCI drug combinations requiring analysis for chemical compatibility and stability. UK pharmacy professionals involved in the delivery of care to palliative patients in hospitals and hospices were invited to enter CSCI combinations comprised of two or more drugs onto an electronic database over a 12-month period. In addition, a separate Delphi study with a panel of 15 expert healthcare professionals was completed to identify a maximum of five combinations of drugs used to treat more complex, but less commonly encountered symptoms unlikely to be identified by the national survey. A total of 57 individuals representing 33 separate palliative care services entered 1,945 drug combinations suitable for analysis, with 278 discrete combinations identified. The top 40 drug combinations represented nearly two-thirds of combinations recorded. A total of 23 different drugs were administered in combination and the median number of drugs in a combination was three. The Delphi study identified five combinations for the relief of complex or refractory symptoms. This study represents the first step towards developing authoritative national guidance on the administration of drugs by CSCI. Further work will ensure healthcare practitioners have the knowledge and confidence that a prescribed combination will be both safe and efficacious.

  14. Pharmacokinetics of detomidine administered to horses at rest and after maximal exercise.

    Science.gov (United States)

    Hubbell, J A E; Sams, R A; Schmall, L M; Robertson, J T; Hinchcliff, K W; Muir, W W

    2009-05-01

    Increased doses of detomidine are required to produce sedation in horses after maximal exercise compared to calm or resting horses. To determine if the pharmacokinetics of detomidine in Thoroughbred horses are different when the drug is given during recuperation from a brief period of maximal exercise compared to administration at rest. Six Thoroughbred horses were preconditioned by exercising them on a treadmill. Each horse ran a simulated race at a treadmill speed that caused it to exercise at 120% of its maximal oxygen consumption. One minute after the end of exercise, horses were treated with detomidine. Each horse was treated with the same dose of detomidine on a second occasion a minimum of 14 days later while standing in a stocks. Samples of heparinised blood were obtained at various time points on both occasions. Plasma detomidine concentrations were determined by liquid chromatography-mass spectrometry. The plasma concentration vs. time data were analysed by nonlinear regression analysis. Median back-extrapolated time zero plasma concentration was significantly lower and median plasma half-life and median mean residence time were significantly longer when detomidine was administered after exercise compared to administration at rest. Median volume of distribution was significantly higher after exercise but median plasma clearance was not different between the 2 administrations. Detomidine i.v. is more widely distributed when administered to horses immediately after exercise compared to administration at rest resulting in lower peak plasma concentrations and a slower rate of elimination. The dose requirement to produce an equivalent effect may be higher in horses after exercise than in resting horses and less frequent subsequent doses may be required to produce a sustained effect.

  15. Differential Gene Expression across Breed and Sex in Commercial Pigs Administered Fenbendazole and Flunixin Meglumine.

    Science.gov (United States)

    Howard, Jeremy T; O'Nan, Audrey T; Maltecca, Christian; Baynes, Ronald E; Ashwell, Melissa S

    2015-01-01

    Characterizing the variability in transcript levels across breeds and sex in swine for genes that play a role in drug metabolism may shed light on breed and sex differences in drug metabolism. The objective of the study is to determine if there is heterogeneity between swine breeds and sex in transcript levels for genes previously shown to play a role in drug metabolism for animals administered flunixin meglumine or fenbendazole. Crossbred nursery female and castrated male pigs (n = 169) spread across 5 groups were utilized. Sires (n = 15) of the pigs were purebred Duroc, Landrace, Yorkshire or Hampshire boars mated to a common sow population. Animals were randomly placed into the following treatments: no drug (control), flunixin meglumine, or fenbendazole. One hour after the second dosing, animals were sacrificed and liver samples collected. Quantitative Real-Time PCR was used to measure liver gene expression of the following genes: SULT1A1, ABCB1, CYP1A2, CYP2E1, CYP3A22 and CYP3A29. The control animals were used to investigate baseline transcript level differences across breed and sex. Post drug administration transcript differences across breed and sex were investigated by comparing animals administered the drug to the controls. Contrasts to determine fold change were constructed from a model that included fixed and random effects within each drug. Significant (P-value fenbendazole, respectively. The current analysis found transcript level differences across swine breeds and sex for multiple genes, which provides greater insight into the relationship between flunixin meglumine and fenbendazole and known drug metabolizing genes.

  16. Pharmacokinetics of intravenously and orally administered sotalol hydrochloride in horses and effects on surface electrocardiogram and left ventricular systolic function.

    Science.gov (United States)

    Broux, B; De Clercq, D; Decloedt, A; De Baere, S; Devreese, M; Van Der Vekens, N; Ven, S; Croubels, S; van Loon, G

    2016-02-01

    Arrhythmias are common in horses. Some, such as frequent atrial or ventricular premature beats, may require long-term anti-arrhythmic therapy. In humans and small animals, sotalol hydrochloride (STL) is often used for chronic oral anti-arrhythmic therapy. STL prolongs repolarization and the effective refractory period in all cardiac tissues. No information on STL pharmacokinetics or pharmacodynamics in horses is available and the aim of this study was to evaluate the pharmacokinetics of intravenously (IV) and orally (PO) administered STL and the effects on surface electrocardiogram and left ventricular systolic function. Six healthy horses were given 1 mg STL/kg bodyweight either IV or PO. Blood samples to determine plasma STL concentrations were taken before and at several time points after STL administration. Electrocardiography and echocardiography were performed at different time points before and after IV STL administration. Mean peak plasma concentrations after IV and PO administration of STL were 1624 ng/mL and 317 ng/mL, respectively. The oral bioavailability was intermediate (48%) with maximal absorption after 0.94 h, a moderate distribution and a mean elimination half-life of 15.24 h. After IV administration, there was a significant increase in QT interval, but no significant changes in other electrocardiographic and echocardiographic parameters. Transient transpiration was observed after IV administration, but no adverse effects were noted after a single oral dose of 1 mg/kg STL in any of the horses. It was concluded that STL has an intermediate oral bioavailability in the horse and might be useful in the treatment of equine arrhythmias. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Immunogenicity and safety of a CRM-conjugated meningococcal ACWY vaccine administered concomitantly with routine vaccines starting at 2 months of age.

    Science.gov (United States)

    Nolan, Terry M; Nissen, Michael D; Naz, Aftab; Shepard, Julie; Bedell, Lisa; Hohenboken, Matthew; Odrljin, Tatjana; Dull, Peter M

    2014-01-01

    Infants are at the highest risk for meningococcal disease and a broadly protective and safe vaccine is an unmet need in this youngest population. We evaluated the immunogenicity and safety of a 4-dose infant/toddler regimen of MenACWY-CRM given at 2, 4, 6, and 12 months of age concomitantly with pentavalent diphtheria-tetanus-acellular pertussis-Hemophilus influenzae type b-inactivated poliovirus-combination vaccine (DTaP-IPV/Hib), hepatitis B vaccine (HBV), 7- or 13-valent conjugate pneumococcal vaccine (PCV), and measles, mumps, and rubella vaccine (MMR). Four doses of MenACWY-CRM induced hSBA titers ≥8 in 89%, 95%, 97%, and 96% of participants against serogroups A, C, W-135, and Y, respectively. hSBA titers ≥8 were present in 76-98% of participants after the first 3 doses. A categorical linear analysis incorporating vaccine group and study center showed responses to routine vaccines administered with MenACWY-CRM were non-inferior to routine vaccines alone, except for seroresponse to the pertussis antigen fimbriae. The reactogenicity profile was not affected when MenACWY-CRM was administered concomitantly with routine vaccines. MenACWY-CRM administered with routine concomitant vaccinations in young infants was well tolerated and induced highly immunogenic responses against each of the serogroups without significant interference with the immune responses to routine infant vaccinations. Healthy 2 month old infants were randomized to receive MenACWY-CRM with routine vaccines (n = 258) or routine vaccines alone (n = 271). Immunogenicity was assessed by serum bactericidal assay using human complement (hSBA). Medically attended adverse events (AEs), serious AEs (SAEs) and AEs leading to study withdrawal were collected throughout the study period.

  18. Internet-versus group-administered cognitive behaviour therapy for panic disorder in a psychiatric setting: a randomised trial

    OpenAIRE

    Bergstrom, Jan; Andersson, Gerhard; Ljotsson, Brjann; Ruck, Christian; Andreewitch, Sergej; Karlsson, Andreas; Carlbring, Per; Andersson, Erik; Lindefors, Nils

    2010-01-01

    Background: Internet administered cognitive behaviour therapy (CBT) is a promising new way to deliver psychological treatment, but its effectiveness in regular care settings and in relation to more traditional CBT group treatment has not yet been determined. The primary aim of this study was to compare the effectiveness of Internet- and group administered CBT for panic disorder (with or without agoraphobia) in a randomised trial within a regular psychiatric care setting. The second aim of the...

  19. Effect of packing on changes in erythrocyte osmotic fragility and malondialdehyde concentration in donkeys administered with ascorbic acid

    OpenAIRE

    Folashade Olaifa; Joseph O. Ayo; Suleiman F. Ambali; Peter I. Rekwot

    2012-01-01

    Experiments were performed with the aim of investigating the effect of packing on erythrocyte osmotic fragility (EOF) and malondialdehyde (MDA) concentration in donkeys, and the effect of ascorbic acid (AA). Twelve apparently healthy donkeys raised under the traditional extensive system served as experimental subjects. Six donkeys administered orally with AA (200 mg/kg) and subjected to packing were used as experimental animals, whilst six others not administered with AA served as contro...

  20. Effects of corn oil administered orally on conspicuity of ultrasonographic small intestinal lesions in dogs with lymphangiectasia.

    Science.gov (United States)

    Pollard, Rachel E; Johnson, Eric G; Pesavento, Patricia A; Baker, Tomas W; Cannon, Allison B; Kass, Philip H; Marks, Stanley L

    2013-01-01

    Lymphangiectasia is one of the causes of protein-losing enteropathy in dogs and characteristic ultrasonographic small intestinal lesions have been previously described. The purpose of this study was to determine whether corn oil administered orally (COAO) would result in increased conspicuity of these characteristic small intestinal ultrasonographic lesions in dogs with lymphangiectasia. Affected dogs were included if they underwent corn oil administered orally and had a surgical full-thickness intestinal biopsy diagnosis of lymphangiectasia. Control dogs had normal clinical examination and standard laboratory test findings. Ultrasound images of duodenum, jejunum, and ileum were obtained prior to and 30, 60, 90, and 120 min after corn oil administered orally for all dogs. Parameters recorded for each ultrasound study were intestinal wall thickness, mucosal echogenicity, and presence or absence of hyperechoic mucosal striations (HMS) and a parallel hyperechoic mucosal line (PHML). Nine affected and five controls dogs were included in the study. Seven of the nine dogs with lymphangiectasia had hyperechoic mucosal striations prior to corn oil administered orally. Jejunal hyperechoic mucosal striations were significantly associated with lymphangiectasia at multiple time points (P dogs with lymphangiectasia 60 or 90 min after corn oil administered orally. Increased mucosal echogenicity was observed in all dogs at multiple time points after corn oil administered orally. A parallel hyperechoic mucosal line was present in the jejunum in 4/5 healthy and 6/9 dogs with lymphangiectasia at one or more time points after corn oil administered orally. Findings indicated that corn oil administered orally improves conspicuity of characteristic ultrasonographic lesions in dogs with lymphangiectasia, however some of these lesions may also be present in healthy dogs that recently received a fatty meal. © 2013 Veterinary Radiology & Ultrasound.

  1. Using computer-assisted survey instruments instead of paper and pencil increased completeness of self-administered sexual behavior questionnaires.

    Science.gov (United States)

    Spark, Simone; Lewis, Dyani; Vaisey, Alaina; Smyth, Eris; Wood, Anna; Temple-Smith, Meredith; Lorch, Rebecca; Guy, Rebecca; Hocking, Jane

    2015-01-01

    To compare the data quality, logistics, and cost of a self-administered sexual behavior questionnaire administered either using a computer-assisted survey instrument (CASI) or by paper and pencil in a primary care clinic. A self-administered sexual behavior questionnaire was administered to 16-29 year olds attending general practice. Questionnaires were administered by either paper and pencil (paper) or CASI. A personal digital assistant was used to self-administer the CASI. A total of 4,491 people completed the questionnaire, with 46.9% responses via CASI and 53.2% by paper. Completion of questions was greater for CASI than for paper for sexual behavior questions: number of sexual partners [odds ratio (OR), 6.85; 95% confidence interval (CI): 3.32, 14.11] and ever having had sex with a person of the same gender (OR, 2.89; 95% CI: 1.52, 5.49). The median number of questions answered was higher for CASI than for paper (17.6 vs. 17.2; P questionnaire compared with $11.83 for paper. Electronic devices using CASI are a tool that can increase participants' questionnaire responses and deliver more complete data for a sexual behavior questionnaire in primary care clinics. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Gquest: modeling patient questionnaires and administering them through a mobile platform application.

    Science.gov (United States)

    Lanzola, G; Ginardi, M G; Mazzanti, A; Quaglini, S

    2014-11-01

    The use of surveys is becoming popular in the health care industry for acquiring information useful to the accomplishment of several studies. Besides their exploitation on a large scale for conducting epidemiological studies, surveys are being increasingly carried out on a narrower perspective through the administration of questionnaires aimed at assessing the quality of life perceived by patients or their clinical status during mid- or long-term treatments. This is useful for managing resources or optimizing and individualizing treatments. This paper describes Gquest, a platform for modeling, generating and administering questionnaires through mobile devices such as smartphones or tablets. Gquest was motivated by the need of administering questionnaires during home treatments, albeit its applicability is rather general. The main requirement was to have a very simple, clean and easy to use platform able to support (a) physicians in the design and delivery of questionnaires and (b) outpatients in sending self-recorded outcomes to the clinical staff. Gquest has two basic components. The first one is a model devised for representing questionnaires which is extremely flexible. It allows the generation of questions and answers of different types, supports adaptivity in the dialog with the user and enforces simple consistency rules for checking his input. The second component is an application able to run instances of those questionnaires. It downloads questionnaires over the air in terms of XML files from a server and stores them locally into the mobile repository. Questionnaires become then available to the user, who in our case is a patient or one of his relatives. The user can select which one to fill-in, according to his needs and/or the specific treatment protocol. The selected questionnaire may be filled-in all at once or be completed in subsequent steps over time since any input provided is persisted on a local database. Finally, when a questionnaire is closed

  3. Brachytherapy Application With In Situ Dose Painting Administered by Gold Nanoparticle Eluters

    International Nuclear Information System (INIS)

    Sinha, Neeharika; Cifter, Gizem; Sajo, Erno; Kumar, Rajiv; Sridhar, Srinivas; Nguyen, Paul L.; Cormack, Robert A.; Makrigiorgos, G. Mike; Ngwa, Wilfred

    2015-01-01

    Purpose: Recent studies show promise that administering gold nanoparticles (GNP) to tumor cells during brachytherapy could significantly enhance radiation damage to the tumor. A new strategy proposed for sustained administration of the GNP in prostate tumors is to load them into routinely used brachytherapy spacers for customizable in situ release after implantation. This in silico study investigated the intratumor biodistribution and corresponding dose enhancement over time due to GNP released from such GNP-loaded brachytherapy spacers (GBS). Method and Materials: An experimentally determined intratumoral diffusion coefficient (D) for 10-nm nanoparticles was used to estimate D for other sizes by using the Stokes-Einstein equation. GNP concentration profiles, obtained using D, were then used to calculate the corresponding dose enhancement factor (DEF) for each tumor voxel, using dose painting-by-numbers approach, for times relevant to the considered brachytherapy sources' lifetimes. The investigation was carried out as a function of GNP size for the clinically applicable low-dose-rate brachytherapy sources iodine-125 (I-125), palladium-103 (Pd-103), and cesium-131 (Cs-131). Results: Results showed that dose enhancement to tumor voxels and subvolumes during brachytherapy can be customized by varying the size of GNP released or eluted from the GBS. For example, using a concentration of 7 mg/g GNP, significant DEF (>20%) could be achieved 5 mm from a GBS after 5, 12, 25, 46, 72, 120, and 195 days, respectively, for GNP sizes of 2, 5, 10, 20, 30, and 50 nm and for 80 nm when treating with I-125. Conclusions: Analyses showed that using Cs-131 provides the highest dose enhancement to tumor voxels. However, given its relatively longer half-life, I-125 presents the most flexibility for customizing the dose enhancement as a function of GNP size. These findings provide a useful reference for further work toward development of potential new brachytherapy application

  4. Effects of orally administered undenatured type II collagen against arthritic inflammatory diseases: a mechanistic exploration.

    Science.gov (United States)

    Bagchi, D; Misner, B; Bagchi, M; Kothari, S C; Downs, B W; Fafard, R D; Preuss, H G

    2002-01-01

    Arthritis afflicts approximately 43 million Americans or approximately 16.6% of the US population. The two most common and best known types of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA). A significant amount of scientific research has been done in attempts to explain what initiates forms of arthritis, how it is promoted and perpetuated and how to effectively intervene in the disease process and promote cartilage remodeling. Current pharmacological strategies mainly address immune suppression and antiinflammatory mechanisms and have had limited success. Recent research provides evidence that alterations in the three-dimensional configuration of glycoproteins are responsible for the recognition/response signaling that catalyzes T-cell attack. Oral administration of autoantigens has been shown to suppress a variety of experimentally induced autoimmune pathologies, including antigen-induced RA. The interaction between gut-associated lymphoid tissue in the duodenum and epitopes of orally administered undenatured type II collagen facilitates oral tolerance to the antigen and stems systemic T-cell attack on joint cartilage. Previous studies have shown that small doses of orally administered undenatured type II chicken collagen effectively deactivate killer T-cell attack. A novel glycosylated undenatured type II collagen material (UC-II) was developed to preserve biological activity. The presence of active epitopes in the UC-II collagen is confirmed by an enzyme-linked immunosorbent assay test and distinguishes this form from hydrolyzed or denatured collagen. Oral intake of small amounts of glycosylated UC-II presents active epitopes, with the correct three-dimensional structures, to Peyer's patches, which influences the signaling required for the development of immune tolerance. UC-II has demonstrated the ability to induce tolerance, effectively reducing joint pain and swelling in RA subjects. A pilot study was conducted for 42 days to evaluate the

  5. Food effects in paediatric medicines development for products Co-administered with food.

    Science.gov (United States)

    Batchelor, Hannah; Kaukonen, Ann Marie; Klein, Sandra; Davit, Barbara; Ju, Rob; Ternik, Robert; Heimbach, Tycho; Lin, Wen; Wang, Jian; Storey, David

    2018-02-05

    A small amount of food is commonly used to aid administration of medicines to children to improve palatability and/or swallowability. However the impact of this co-administered food on the absorption and subsequent pharmacokinetic profile of the drug is unknown. Existing information on food effects is limited to standard protocols used to evaluate the impact of a high fat meal in an adult population using the adult medication. In the absence of a substantial body of data, there are no specific guidelines available during development of paediatric products relating to low volumes of potentially low calorie food. This paper brings together expertise to consider how the impact of co-administered food can be risk assessed during the development of a paediatric medicine. Two case studies were used to facilitate discussions and seek out commonalities in risk assessing paediatric products; these case studies used model drugs that differed in their solubility, a poorly soluble drug that demonstrated a positive food effect in adults and a highly soluble drug where a negative food effect was observed. For poorly soluble drugs risk assessments are centred upon understanding the impact of food on the in vivo solubility of the drug which requires knowledge of the composition of the food and the volumes present within the paediatric gastrointestinal tract. Further work is required to develop age appropriate in vitro and in silico models that are representative of paediatric populations. For soluble drugs it is more important to understand the mechanisms that may lead to a food effect, this may include interactions with transporters or the impact of the food composition on gastro-intestinal transit or even altered gastric motility. In silico models have the most promise for highly soluble drug products although it is essential that these models reflect the relevant mechanisms involved in potential food effects. The development of appropriate in vitro and in silico tools is

  6. Brachytherapy Application With In Situ Dose Painting Administered by Gold Nanoparticle Eluters

    Energy Technology Data Exchange (ETDEWEB)

    Sinha, Neeharika [Department of Sciences, Wentworth Institute of Technology, Boston, Massachusetts (United States); Cifter, Gizem [Department of Physics and Applied Physics, University of Massachusetts, Lowell, Massachusetts (United States); Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital and Harvard Medical School, Boston, Massachusetts (United States); Sajo, Erno [Department of Physics and Applied Physics, University of Massachusetts, Lowell, Massachusetts (United States); Kumar, Rajiv; Sridhar, Srinivas [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital and Harvard Medical School, Boston, Massachusetts (United States); Electronic Materials Research Institute and Department of Physics, Northeastern University, Boston, Massachusetts (United States); Nguyen, Paul L.; Cormack, Robert A.; Makrigiorgos, G. Mike [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital and Harvard Medical School, Boston, Massachusetts (United States); Ngwa, Wilfred, E-mail: wngwa@lroc.harvard.edu [Department of Physics and Applied Physics, University of Massachusetts, Lowell, Massachusetts (United States); Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital and Harvard Medical School, Boston, Massachusetts (United States)

    2015-02-01

    Purpose: Recent studies show promise that administering gold nanoparticles (GNP) to tumor cells during brachytherapy could significantly enhance radiation damage to the tumor. A new strategy proposed for sustained administration of the GNP in prostate tumors is to load them into routinely used brachytherapy spacers for customizable in situ release after implantation. This in silico study investigated the intratumor biodistribution and corresponding dose enhancement over time due to GNP released from such GNP-loaded brachytherapy spacers (GBS). Method and Materials: An experimentally determined intratumoral diffusion coefficient (D) for 10-nm nanoparticles was used to estimate D for other sizes by using the Stokes-Einstein equation. GNP concentration profiles, obtained using D, were then used to calculate the corresponding dose enhancement factor (DEF) for each tumor voxel, using dose painting-by-numbers approach, for times relevant to the considered brachytherapy sources' lifetimes. The investigation was carried out as a function of GNP size for the clinically applicable low-dose-rate brachytherapy sources iodine-125 (I-125), palladium-103 (Pd-103), and cesium-131 (Cs-131). Results: Results showed that dose enhancement to tumor voxels and subvolumes during brachytherapy can be customized by varying the size of GNP released or eluted from the GBS. For example, using a concentration of 7 mg/g GNP, significant DEF (>20%) could be achieved 5 mm from a GBS after 5, 12, 25, 46, 72, 120, and 195 days, respectively, for GNP sizes of 2, 5, 10, 20, 30, and 50 nm and for 80 nm when treating with I-125. Conclusions: Analyses showed that using Cs-131 provides the highest dose enhancement to tumor voxels. However, given its relatively longer half-life, I-125 presents the most flexibility for customizing the dose enhancement as a function of GNP size. These findings provide a useful reference for further work toward development of potential new brachytherapy application

  7. Barriers for administering primary health care services to battered women: Perception of physician and nurses

    Directory of Open Access Journals (Sweden)

    Eman H. Alsabhan

    2011-12-01

    Full Text Available Background: Violence against women is an important public-health problem that draws attention of a wide spectrum of clinicians. However, multiple barriers undermine the efforts of primary health care workers to properly manage and deal with battered women. Objectives: The aim of the present study was to reveal barriers that might impede administering comprehensive health care to battered women and compare these barriers between nurses and physicians and identify factors affecting such barriers. Methods: A total of 1553 medical staff from 78 primary health care units agreed to share in this study, of these 565 were physicians and 988 were nurses. Results: Barriers related to the battered woman topped the list of ranks for both physicians (93.1 ± 17.4% and nurses (82.1 ± 29.3%. Institutional barriers (87.2 ± 21.5%, barriers related to the health staff (79.8 ± 20. 5%, and social barriers (77.5 ± 21.7% followed, respectively, in the rank list of physicians while for the list of nurses, social barriers (75.1 ± 30.1%, institutional barriers (74.3 ± 31.7% followed with barriers related to health staff (70.0 ± 30.0% at the bottom of the list. Only duration spent at work and degree of education of nurses were significantly affecting the total barrier score, while these factors had no significant association among physicians. Conclusion: Real barriers exist that might interfere with administering proper comprehensive health care at the primary health care units by both physicians and nurses. This necessitates design of specific programs to improve both the knowledge and skills of the medical staff to deal with violence among women. Also, available resources and infrastructure must be strengthened to face this problem and enable primary health care staff to care for battered women. Keywords: Battered women, Barriers, Physicians, Nurses, Primary health care

  8. Differential Gene Expression across Breed and Sex in Commercial Pigs Administered Fenbendazole and Flunixin Meglumine.

    Directory of Open Access Journals (Sweden)

    Jeremy T Howard

    Full Text Available Characterizing the variability in transcript levels across breeds and sex in swine for genes that play a role in drug metabolism may shed light on breed and sex differences in drug metabolism. The objective of the study is to determine if there is heterogeneity between swine breeds and sex in transcript levels for genes previously shown to play a role in drug metabolism for animals administered flunixin meglumine or fenbendazole. Crossbred nursery female and castrated male pigs (n = 169 spread across 5 groups were utilized. Sires (n = 15 of the pigs were purebred Duroc, Landrace, Yorkshire or Hampshire boars mated to a common sow population. Animals were randomly placed into the following treatments: no drug (control, flunixin meglumine, or fenbendazole. One hour after the second dosing, animals were sacrificed and liver samples collected. Quantitative Real-Time PCR was used to measure liver gene expression of the following genes: SULT1A1, ABCB1, CYP1A2, CYP2E1, CYP3A22 and CYP3A29. The control animals were used to investigate baseline transcript level differences across breed and sex. Post drug administration transcript differences across breed and sex were investigated by comparing animals administered the drug to the controls. Contrasts to determine fold change were constructed from a model that included fixed and random effects within each drug. Significant (P-value <0.007 basal transcript differences were found across breeds for SULT1A1, CYP3A29 and CYP3A22. Across drugs, significant (P-value <0.0038 transcript differences existed between animals given a drug and controls across breeds and sex for ABCB1, PS and CYP1A2. Significant (P <0.0038 transcript differences across breeds were found for CYP2E1 and SULT1A1 for flunixin meglumine and fenbendazole, respectively. The current analysis found transcript level differences across swine breeds and sex for multiple genes, which provides greater insight into the relationship between flunixin

  9. Death on demand? An analysis of physician-administered euthanasia in The Netherlands.

    Science.gov (United States)

    Preston, Robert

    2018-03-01

    Physician-administered euthanasia (PAE) was legalized, along with physician-assisted suicide (PAS), in The Netherlands in 2001. Annual reports of the Dutch Regional Euthanasia Review Committees, the committees' 2015 published Code of Practice and research studies. There is a general openness about the practice of PAE/PAS in The Netherlands and an avoidance of misleading euphemisms. The 2001 law also includes arrangements for post-event review of PAE/PAS decisions. Rising numbers of annually reported deaths from PAE and uncertainty over actual numbers. Movement away from the principle that euthanasia must take place within an established doctor-patient relationship. Increasing extension of the 2001 law to people with mental health conditions, dementia and multiple co-morbidities. Nature of the post-event scrutiny applied to reported cases. The predominance of PAE over PAS where both are legalized raises questions over how these two acts are perceived and whether there are implications for such laws. Are the criteria for PAE/PAS in the 2001 law appropriate for a law of this nature? What should be the respective roles of the second-opinion doctors and the review committees?

  10. Antimalarial Activity of Orally Administered Curcumin Incorporated in Eudragit®-Containing Liposomes

    Directory of Open Access Journals (Sweden)

    Elisabet Martí Coma-Cros

    2018-05-01

    Full Text Available Curcumin is an antimalarial compound easy to obtain and inexpensive, having shown little toxicity across a diverse population. However, the clinical use of this interesting polyphenol has been hampered by its poor oral absorption, extremely low aqueous solubility and rapid metabolism. In this study, we have used the anionic copolymer Eudragit® S100 to assemble liposomes incorporating curcumin and containing either hyaluronan (Eudragit-hyaluronan liposomes or the water-soluble dextrin Nutriose® FM06 (Eudragit-nutriosomes. Upon oral administration of the rehydrated freeze-dried nanosystems administered at 25/75 mg curcumin·kg−1·day−1, only Eudragit-nutriosomes improved the in vivo antimalarial activity of curcumin in a dose-dependent manner, by enhancing the survival of all Plasmodium yoelii-infected mice up to 11/11 days, as compared to 6/7 days upon administration of an equal dose of the free compound. On the other hand, animals treated with curcumin incorporated in Eudragit-hyaluronan liposomes did not live longer than the controls, a result consistent with the lower stability of this formulation after reconstitution. Polymer-lipid nanovesicles hold promise for their development into systems for the oral delivery of curcumin-based antimalarial therapies.

  11. Orally administered conjugated linoleic acid ameliorates allergic dermatitis induced by repeated applications of oxazolone in mice.

    Science.gov (United States)

    Nakanishi, Tomonori; Tokunaga, Yuzo; Yamasaki, Masao; Erickson, Laurie; Kawahara, Satoshi

    2016-12-01

    Conjugated linoleic acid (CLA) is one of the constituents of animal products with possible health benefits such as anti-carcinogenic and anti-obesity effects. In this study, we investigated the immunomodulatory effects of CLA using a mouse model of allergic dermatitis. Mice were orally administered either a CLA mixture containing equal amounts of 9c, 11 t-CLA and 10 t, 12c-CLA, or high linoleic acid safflower oil, and allergic dermatitis was induced on the ear by repeated topical applications of oxazolone. Oral administration of the CLA mixture but not the high linoleic safflower oil attenuated the symptoms of allergic dermatitis in both ear weights and clinical scores. This effect was associated with decreased levels of ear interleukin-4 (IL-4) and plasma immunoglobulin E. The immunomodulatory effects of the CLA isomers were compared by an in vitro cytokine production assay. The results showed that 9c, 11 t-CLA, the most predominant isomer in animal products, significantly inhibited IL-4 and interferon-γ production from mouse splenocytes with similar potency to 10 t, 12c-CLA. These findings suggest that CLA, a constituent of animal products, has a potentially beneficial effect for amelioration of allergic dermatitis. © 2016 Japanese Society of Animal Science.

  12. Portosystemic shunting in portal hypertension: evaluation with portal scintigraphy with transrectally administered I-123 IMP

    International Nuclear Information System (INIS)

    Kashiwagi, T.; Azuma, M.; Ikawa, T.; Takehara, T.; Matsuda, H.; Yoshioka, H.; Mitsutani, N.; Koizumi, T.; Kimura, K.

    1988-01-01

    Portosystemic shunting was evaluated with rectal administration of iodine-123 iodoamphetamine (IMP) in seven patients without liver disease and 53 patients with liver cirrhosis. IMP (2-3 mCi [74-111 MBq]) was administered to the rectum through a catheter. Images of the chest and abdomen were obtained for up to 60 minutes with a scintillation camera interfaced with a computer. In all patients, images of the liver and/or lungs were observed within 5-10 minutes and became clear with time. In patients without liver disease, only liver images could be obtained, whereas the lung was visualized with or without the liver in all patients with liver cirrhosis. The portosystemic shunt index was calculated by dividing counts of lungs by counts of liver and lung. These values were significantly higher in liver cirrhosis, especially in the decompensated stage. Transrectal portal scintigraphy with IMP appears to be a useful method for noninvasive and quantitative evaluation of portosystemic shunting in portal hypertension

  13. Regulatory analysis on criteria for the release of patients administered radioactive material. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, S.; McGuire, S.A.

    1997-02-01

    This regulatory analysis was developed to respond to three petitions for rulemaking to amend 10 CFR parts 20 and 35 regarding release of patients administered radioactive material. The petitions requested revision of these regulations to remove the ambiguity that existed between the 1-millisievert (0.1-rem) total effective dose equivalent (TEDE) public dose limit in Part 20, adopted in 1991, and the activity-based release limit in 10 CFR 35.75 that, in some instances, would permit release of individuals in excess of the current public dose limit. Three alternatives for resolution of the petitions were evaluated. Under Alternative 1, NRC would amend its patient release criteria in 10 CFR 35.75 to match the annual public dose limit in Part 20 of 1 millisievert (0.1 rem) TEDE. Alternative 2 would maintain the status quo of using the activity-based release criteria currently found in 10 CFR 35.75. Under Alternative 3, the NRC would revise the release criteria in 10 CFR 35.75 to specify a dose limit of 5 millisieverts (0.5 rem) TEDE.

  14. Chronically administered 3-nitropropionic acid produces selective lesions in the striatum and reduces muscle tonus.

    Science.gov (United States)

    Shimano, Y; Kumazaki, M; Sakurai, T; Hida, H; Fujimoto, I; Fukuda, A; Nishino, H

    1995-12-01

    Systemically administered 3-nitropropionic acid (3- NPA), irreversible inhibitor of succinate dehydrogenase, produced characteristic bilateral lesions in the striatum (STR) in the rat. Inside the lesion, neutrophils invaded and strong immunoreaction for IgG as well as complement factor C3b/C4b receptor (C3b/C4br) were observed. The core of the lesion lost the immunoreaction for glial fibrillary acidic protein (GFAP) while the marginal area had abundant GFAP-labeled astrocytes around the vessels. Intoxicated rats often became somnolent and were awkward in cooperative movement on a pole climbing test, but they had a quite good memory retention in a passive avoidance learning. Muscle tonus in some of the intoxicated rats became hypotonic with low voltage electromyogram (EMG) activity, especially in lower limbs. In summary, 3-NPA intoxicated rats had selective bilateral lesions in the STR and exhibited disturbances in a cooperative movement owing to the impairment in muscle tonus, thus it would be a useful animal model to deduce the central pathogenesis of Huntington's disease.

  15. Comparison of radioisotopic studied calcium metabolism in the orally administered and inhaled cadmium rat

    International Nuclear Information System (INIS)

    Fauran-Clavel, M.J.; Oustrin, J.; Godin, J.; Boudene, C.

    1982-01-01

    The radioisotopic study of calcium metabolism in the rat after oral administration of cadmium, 8 mg/kg during 13 weeks, has shown two different effects of this ion: 1) in the intestine, cadmium inhibits the absorption of calcium by active transport; 2) in the deep bone compartment, the decrease of the bone calcium used for the crystallization and slowly exchangeable with the calcium central pool (serum, extracellular and soft tissues calcium) is combined with a reduction of the exchange rates between the two compartments. When administered through a microparticle aerosol inhalation (1 mg/m 3 of air, 30 mn a day, during 12 weeks), cadmium's main target organ is the deep bone compartment. For both modes of administration, the slowing down of osteogenesis is confirmed by a drop in serum alkaline phosphatase after a four weeks period which reflects a decrease of the osteoblastic activity. Therefore it appears that the effects on bones observed during the chronic oral cadmium administration, do not result from a malabsorption of intestine calcium but also from the very action the Cd ++ ion on the bone crystallization process [fr

  16. Effect of acetate Ringer's solution with or without 5% dextrose administered intravenously to diarrheic calves.

    Science.gov (United States)

    Tsukano, Kenji; Kato, Satoko; Sarashina, Shinya; Abe, Izumi; Ajito, Tadaharu; Ohtsuka, Hiromichi; Suzuki, Kazuyuki

    2017-04-20

    The objectives of this study were to evaluate the effects of intravenous acetate Ringer's solution, with or without dextrose, on diarrheic calves with either experimentally induced or spontaneous diarrhea. In the experimental model, diarrhea was induced in nine healthy calves by administering cold milk (below 4°C) twice a day for 2 days. The calves were randomly assigned to the isotonic saline (ISS), acetated Ringer's (AR) or acetated Ringer's with 5% dextrose (ARD) groups, with three calves assigned to each group. The calves received 80 ml/kg of their designated solution, at a flow rate of 20 ml/kg/hr. Infusion of ISS, AR and ARD were all found to be safe and effective in increasing plasma volume. Intravenous (IV) infusion of ISS resulted in the acidification secondary to dilution, while AR and ARD infusion inhibited acidification. In addition, prevention of catabolism was observed only with IV infusion of ARD. Sixteen calves with spontaneous diarrhea were enrolled in the clinical study. The calves were randomly assigned to the AR or ARD groups, with eight calves being assigned to each group. The calves received 100 ml/kg of their designated solution, at a flow rate of 25 ml/kg/hr. Intravenous infusion of AR and ARD was found to be effective in increasing plasma volume and inhibiting acidification. Only infusion of ARD prevented catabolism, but it also led to hyperglycemia. Our results suggest that a solution containing dextrose may be beneficial for wasting diarrheic calves.

  17. Reducing children's social anxiety symptoms: exploring a novel parent-administered cognitive bias modification training intervention.

    Science.gov (United States)

    Lau, Jennifer Y F; Pettit, Eleanor; Creswell, Cathy

    2013-07-01

    Social fears and worries in children are common and impairing. Yet, questions have been raised over the efficacy, suitability and accessibility of current frontline treatments. Here, we present data on the effectiveness of a novel parent-administered Cognitive Bias Modification of Interpretations (CBM-I) training tool. CBM-I capitalises on findings demonstrating an association between anxiety symptoms and biased interpretations, the tendency to interpret ambiguous situations negatively. Through CBM-I training, participants are exposed to benign resolutions, and reinforced for selecting these. In adults and adolescents, CBM-I training is effective at reducing symptoms and mood reactivity. In the present study, we developed a novel, child-appropriate form of CBM-I training, by presenting training materials within bedtime stories, read by a parent to the child across three consecutive evenings. Compared to a test-retest control group (n = 17), children receiving CBM-I (n = 19) reported greater endorsement of benign interpretations of ambiguous situations post-training (compared to pre-training). These participants (but not the test-retest control group) also showed a significant reduction in social anxiety symptoms. Pending replication and extensions to a clinical sample, these data may implicate a cost-effective, mechanism-driven and developmentally-appropriate resource for targeting social anxiety problems in children. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Neurologic complications of intrathecal liposomal cytarabine administered prophylactically to patients with non-Hodgkin lymphoma.

    Science.gov (United States)

    Gállego Pérez-Larraya, Jaime; Palma, José Alberto; Carmona-Iragui, María; Fernández-Torrón, Roberto; Irimia, Pablo; Rodríguez-Otero, Paula; Panizo, Carlos; Martínez-Vila, Eduardo

    2011-07-01

    Central nervous system (CNS) prophylaxis is required during initial treatment of non-Hodgkin lymphoma (NHL) subtypes that carry a high risk of CNS involvement. Intrathecal (IT) liposomal cytarabine, a formulation with prolonged half-life, has been shown to be safe and effective in the treatment of meningeal disease in patients with high-grade lymphoma. We retrospectively reviewed all adult patients with high-grade NHL that received prophylactic therapy with IT liposomal cytarabine and developed neurologic complications in our institution between April 2007 and May 2009. We recorded information on hospital admission, chemotherapy regimens, clinical features, neuroimaging, cerebrospinal fluid, neurophysiology data, and outcome. Neurotoxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC). Four of fourteen patients (28%) developed moderate or severe neurotoxicity (grades 2 and 3 of the NCI-CTC), manifested as conus medullaris/cauda equine syndrome or pseudotumour cerebri-like syndrome, after a median of 3.5 IT courses of liposomal cytarabine. All patients had received corticosteroids to prevent arachnoiditis. Liposomal cytarabine given via the IT route, even with concomitant corticosteroid administration, can result in significant neurotoxicity in some patients. We discuss the potential pathogenesis of these effects and suggest hypothetical therapeutic measures to prevent these complications. Specialists should be aware of these possible complications when administering prophylactic IT liposomal cytarabine in high-grade NHL patients, and additional prospective studies should be conducted to more clearly delineate the frequency and characteristics of these complications.

  19. Examining various subthreshold definitions of PTSD using the Clinician Administered PTSD Scale for DSM-5.

    Science.gov (United States)

    Franklin, C Laurel; Raines, Amanda M; Chambliss, Jessica L; Walton, Jessica L; Maieritsch, Kelly P

    2018-07-01

    The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5; American Psychiatric Association [APA], 2013) includes Other- and Unspecified- Trauma and Stressor-Related Disorders to capture subthreshold Posttraumatic Stress Disorder (PTSD) symptoms. However, the DSM-5 does not specify the number or type of symptoms needed to assign them. The purpose of the current study was to extend our understanding of subthreshold PTSD by comparing four commonly used definitions adapted to the DSM-5 PTSD criteria in an outpatient treatment-seeking sample. Veterans (N = 193) presenting to PTSD clinics were assessed using the Clinician Administered PTSD Scale for DSM-5 (CAPS-5). Participants reported a criterion A traumatic event, but did not meet criteria for threshold-PTSD. We hypothesized that the number of veterans captured would be highest when fewer specific criterion sets were required by the subthreshold definition. Our hypothesis was upheld in that the more criteria required by the subthreshold PTSD definition, the lower the number of veterans counted within the group. The study consisted primarily of trauma treatment-seeking male veterans, with chronic PTSD symptoms. In addition, the sample size was small and was collected as part of routine clinical care. These results support previous contentions around careful decision making when defining what constitutes subthreshold PTSD in research and clinical work. It also points to the need for continued research to better understand the diagnostic and treatment implications of subthreshold PTSD. Published by Elsevier B.V.

  20. Tissue distribution and excretion of copper-67 intraperitoneally administered to rats fed fructose or starch

    International Nuclear Information System (INIS)

    Holbrook, J.; Fields, M.; Smith, J.C. Jr.; Reiser, S.

    1986-01-01

    It has been suggested that impaired gut absorption of copper is the cause of the exacerbated copper deficiency signs in rats fed fructose when compared to rats fed starch. The present study was designed to examine how rats fed fructose or starch diets, either copper-deficient or supplemented, distributed and excreted 67 Cu when the isotope was administered i.p. Intraperitoneal administration was chosen in an effort to circumvent primary gut absorption as a factor in the metabolism of 67 Cu. After 7 wk of dietary treatment, rats received an i.p. injection of 67 Cu and were placed in metabolic cages for 4 d. Regardless of dietary carbohydrate, copper-deficient rats retained similar levels of radioactivity in various tissues and excreted similar amounts of 67 Cu in feces and urine. This similarity in copper metabolism in copper-deficient rats fed either fructose or starch when the gut was circumvented for isotope administration suggests that the gut could be responsible, at least in part, for the exacerbated signs associated with the copper deficiency in rats fed fructose. The possibility is discussed that alterations in metabolism may increase the requirement for copper when fructose is the main dietary carbohydrate

  1. Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines

    Directory of Open Access Journals (Sweden)

    Masayuki Hayashi

    2017-02-01

    Full Text Available Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV, a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.

  2. Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination.

    Science.gov (United States)

    Hysek, Cédric M; Simmler, Linda D; Schillinger, Nathalie; Meyer, Nicole; Schmid, Yasmin; Donzelli, Massimiliano; Grouzmann, Eric; Liechti, Matthias E

    2014-03-01

    Methylphenidate and 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') are widely misused psychoactive drugs. Methylphenidate increases brain dopamine and norepinephrine levels by blocking the presynaptic reuptake transporters. MDMA releases serotonin, dopamine and norepinephrine through the same transporters. Pharmacodynamic interactions of methylphenidate and MDMA are likely. This study compared the pharmacodynamic and pharmacokinetic effects of methylphenidate and MDMA administered alone or in combination in healthy subjects using a double-blind, placebo-controlled, crossover design. Methylphenidate did not enhance the psychotropic effects of MDMA, although it produced psychostimulant effects on its own. The haemodynamic and adverse effects of co-administration of methylphenidate and MDMA were significantly higher compared with MDMA or methylphenidate alone. Methylphenidate did not change the pharmacokinetics of MDMA and vice versa. Methylphenidate and MDMA shared some subjective amphetamine-type effects; however, 125 mg of MDMA increased positive mood more than 60 mg of methylphenidate, and methylphenidate enhanced activity and concentration more than MDMA. Methylphenidate and MDMA differentially altered facial emotion recognition. Methylphenidate enhanced the recognition of sad and fearful faces, whereas MDMA reduced the recognition of negative emotions. Additionally, the present study found acute pharmacodynamic tolerance to MDMA but not methylphenidate. In conclusion, the combined use of methylphenidate and MDMA does not produce more psychoactive effects compared with either drug alone, but potentially enhances cardiovascular and adverse effects. The findings may be of clinical importance for assessing the risks of combined psychostimulant misuse. Trial registration identification number: NCT01465685 (http://clinicaltrials.gov/ct2/show/NCT01465685).

  3. Gold nanoparticles and diclofenac diethylammonium administered by iontophoresis reduce inflammatory cytokines expression in Achilles tendinitis.

    Science.gov (United States)

    Dohnert, Marcelo B; Venâncio, Mirelli; Possato, Jonathann C; Zeferino, Rodrigo C; Dohnert, Luciana H; Zugno, Alexandra I; De Souza, Cláudio T; Paula, Marcos M S; Luciano, Thais F

    2012-01-01

    Tendinitis affects a substantial number of people in several occupations involving repetitive work or direct trauma. Iontophoresis is a therapeutic alternative used in the treatment of injury during the inflammatory phase. In recent years, gold nanoparticles (GNP) have been studied due to their therapeutic anti-inflammatory capacity and as an alternative to the transport of several proteins. This study evaluates the therapeutic effects of iontophoresis using GNPs and diclofenac diethylammonium on inflammatory parameters in rats challenged with traumatic tendinitis. Wistar rats were divided in three treatment groups (n = 15): (1) iontophoresis + diclofenac diethylammonium; (2) iontophoresis + GNP; and (3) iontophoresis + diclofenac diethylammonium + GNP. External control was formed by challenged tendons without treatment (n = 15). Iontophoresis was administered using 0.3 mA direct current on 1.5 cm(2) electrodes. The levels of both inflammatory cytokines were significantly higher in untreated challenged rats, when compared with the control (5.398 ± 234 for interleukin 1 beta and 6.411 ± 432 for tumor necrosis factor alpha), which confirms the occurrence of an inflammatory stage in injury (P diclofenac and GNP, results were similar to the control (1.732 ± 239) (P diclofenac and GNPs presented decreased levels, compared with the control (3.221 ± 369) (P < 0.05). The results show the efficacy of drug administration using direct current to treat tendinitis in an animal model, and the potential anti-inflammatory, carrier, and enhancing effects of GNPs in iontophoresis.

  4. [Optimization of ventricular function during anesthesia induction by administering crystalloids and colloids to heart surgery patients].

    Science.gov (United States)

    Ballesteros, M; Boldt, J; Zickmann, B; Knothe, C; Hempelmann, G

    1995-01-01

    To describe the changes in cardiac function after administration of three different solutions infused after anesthetic induction. Thirty-six patients scheduled for elective aortocoronary bypass surgery were randomly distributed into three groups. Over a period of 25 min after anesthetic induction, 12 received 10 ml/kg of Ringer solution (low dose crystalloid group), 12 received 20 ml/kg of Ringer solution (high dose crystalloid group), and 12 received 10 ml/kg of Ringer solution with 10 ml/kg of hydroxi-ethyl-almidon solution 450,000 D, 0.7 substitution grade (group C-HEA). Minute volume, systemic and pulmonary pressures, osmolality of blood and urine, and plasma and urine sodium concentrations were measured before and after infusion of the assigned liquid. In spite of the volume infused, low dose crystalloid group showed a high incidence of oliguria, increased urinary osmolality and decreased sodium in urine. Cardiac and systolic indices and left ventricular work load remained stable after infusion of the assigned liquid in low and high dose crystalloid groups, whereas they increased significantly ion group C-HEA (+23%, +16% and +20%). Administration of restricted doses of crystalloids after anesthetic induction favors the retention of water and sodium. Higher doses of crystalloids weaken this effect. However, neither of these two regimens leads to a more effective cardiac work load. A combination of crystalloids and colloids administered immediately after anesthetic induction temporarily improves cardiac performance during surgery.

  5. In vivo release of bupivacaine from subcutaneously administered oily solution. Comparison with in vitro release

    DEFF Research Database (Denmark)

    Larsen, Dorrit Bjerg; Joergensen, Stig; Olsen, Niels Vidiendal

    2002-01-01

    A non-randomized cross-over study was performed with bupivacaine HCl (5 mg x ml(-1)) aqueous solution and bupivacaine free base (4.44 mg x ml(-1)) in Viscoleo/castor oil 2:1 (v/v) administered s.c. to male Wistar rats. Plasma levels were analyzed by LC-MS. Plasma profiles obtained after...... administration of oily solution showed a prolonged bupivacaine release with lower peak plasma levels as compared to administration of an aqueous formulation applied in the same compartment. t(1/2), t(max), C(max) and AUC(0-infinity) for the aqueous solution were 63+/-8 min, 19+/-16 min, 194+/-46 ng x ml(-1......) and 25,000+/-3000 ng min x ml(-1), respectively, while the corresponding data for the oil solution were 368+/-89 min, 334+/-186 min, 36+/-25 ng x ml(-1) and 25,000+/-6000 ng x min x ml(-1). The present data indicate the potential of designing an oil formulation of bupivacaine with a prolonged local...

  6. Phase I dose-finding study of cabazitaxel administered weekly in patients with advanced solid tumours

    International Nuclear Information System (INIS)

    Fumoleau, Pierre; Trigo, Jose Manuel; Isambert, Nicolas; Sémiond, Dorothée; Gupta, Sunil; Campone, Mario

    2013-01-01

    Cabazitaxel is approved in patients with metastatic hormone-refractory prostate cancer previously treated with a docetaxel-containing regimen. This study evaluated a weekly cabazitaxel dosing regimen. Primary objectives were to report dose-limiting toxicities (DLTs) and to determine the maximum tolerated dose (MTD). Efficacy, safety and pharmacokinetics were secondary objectives. Cabazitaxel was administered weekly (1-hour intravenous infusion at 1.5–12 mg/m2 doses) for the first 4 weeks of a 5-week cycle in patients with solid tumours. Monitoring of DLTs was used to determine the MTD and the recommended weekly dose. Thirty-one patients were enrolled. Two of six patients experienced DLTs at 12 mg/m 2 , which was declared the MTD. Gastrointestinal disorders were the most common adverse event. Eight patients developed neutropenia (three ≥ Grade 3); one occurrence of febrile neutropenia was reported. There were two partial responses (in breast cancer) and 13 patients had stable disease (median duration of 3.3 months). Increases in C max and AUC 0–t were dose proportional for the 6–12 mg/m 2 doses. The MTD of weekly cabazitaxel was 12 mg/m 2 and the recommended weekly dose was 10 mg/m 2 . The observed safety profile and antitumour activity of cabazitaxel were consistent with those observed with other taxanes in similar dosing regimens. The study was registered with ClinicalTrials.gov as http://www.clinicaltrials.gov/ct2/show/NCT01755390

  7. Impact of self-administered relaxation and guided imagery techniques during final trimester and birth.

    Science.gov (United States)

    Gedde-Dahl, Merete; Fors, Egil A

    2012-02-01

    The objective of this study was to test if and how self-administered practice of relaxation techniques, positive affirmation and guided imagery, in the final part of pregnancy had an impact on giving birth. Further to see if the use of a simple method, a CD with a booklet, with no previous training or specific support of the participants (neither required nor delivered), affected the birth experience. Outcome measures were monitored both during and after delivery: During delivery, pain and anxiety were measured at different stages of birth. Post-delivery Wellbeing (Edmonton Scale 0-10, where 10 is the worst possible feeling of Wellbeing), pain, anxiety, Apgar score, duration of birth, complications and anesthesia/analgesic were recorded. Those in the CD-intervention group also reported how many times they had practiced the techniques. The study employed a randomized controlled trial. Results show that the CD-intervention group had a significantly better score on total Wellbeing, as measured by the ESAS (0-10) Edmonton Scale. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Tissular localization and excretion of intravenously administered silica nanoparticles of different sizes

    International Nuclear Information System (INIS)

    Xie Guangping; Sun Jiao; Zhong Gaoren

    2012-01-01

    The nanotoxicology as a new subdiscipline of nanotechnology needs to be studied in vivo. To do so, it is essential to understand certain pharmacological information of the nanoparticles in vivo. Silica nanoparticles (SiNPs) have been developed for a number of biomedical uses; however, research on their tissular localization and excretion has been limited. In this study, we analyzed the localization of intravenously administered SiNPs with sizes of 20 and 80 nm in liver and spleen and quantitatively investigated the excretion of SiNPs through urine and feces. The results of the tissular localization study showed that the SiNPs were located in liver evenly; however, they were mainly accumulated in the white pulp of spleen. The quantitative excretory assay found the renal excretion being the main excretion pathway of SiNPs and indicated that the accumulated excretory rate of 80 nm SiNPs through urine was higher than that of 20 nm SiNPs because of the higher hemoconcentration. Further analysis of radioactive substances in the excreta showed the convincing confirmatory evidence that the SiNPs of both the sizes of 20 and 80 nm could be excreted through urine. These results provide important information on in vivo distribution and excretion of SiNPs.

  9. The hemodynamic effects of methylene blue when administered at the onset of cardiopulmonary bypass.

    Science.gov (United States)

    Maslow, Andrew D; Stearns, Gary; Butala, Parag; Batula, Parag; Schwartz, Carl S; Gough, Jeffrey; Singh, Arun K

    2006-07-01

    Hypotension occurs during cardiopulmonary bypass (CPB), in part because of induction of the inflammatory response, for which nitric oxide and guanylate cyclase play a central role. In this study we examined the hemodynamic effects of methylene blue (MB), an inhibitor of guanylate cyclase, administered during cardiopulmonary bypass (CPB) to patients taking angiotensin-converting enzyme inhibitors. Thirty patients undergoing cardiac surgery were randomized to receive either MB (3 mg/kg) or saline (S) after institution of CPB and cardioplegic arrest. CPB was managed similarly for all study patients. Hemodynamic data were assessed before, during, and after CPB. The use of vasopressors was recorded. All study patients experienced a similar reduction in mean arterial blood pressure (MAP) and systemic vascular resistance (SVR) with the onset of CPB and cardioplegic arrest. MB increased MAP and SVR and this effect lasted for 40 minutes. The saline group demonstrated a persistently reduced MAP and SVR throughout CPB. The saline group received phenylephrine more frequently during CPB, and more norepinephrine after CPB to maintain a desirable MAP. The MB group recorded significantly lower serum lactate levels despite equal or greater MAP and SVR. In conclusion, administration of MB after institution of CPB for patients taking angiotensin-converting enzyme inhibitors increased MAP and SVR and reduced the need for vasopressors. Furthermore, serum lactate levels were lower in MB patients, suggesting more favorable tissue perfusion.

  10. Regulatory analysis on criteria for the release of patients administered radioactive material. Final report

    International Nuclear Information System (INIS)

    Schneider, S.; McGuire, S.A.

    1997-02-01

    This regulatory analysis was developed to respond to three petitions for rulemaking to amend 10 CFR parts 20 and 35 regarding release of patients administered radioactive material. The petitions requested revision of these regulations to remove the ambiguity that existed between the 1-millisievert (0.1-rem) total effective dose equivalent (TEDE) public dose limit in Part 20, adopted in 1991, and the activity-based release limit in 10 CFR 35.75 that, in some instances, would permit release of individuals in excess of the current public dose limit. Three alternatives for resolution of the petitions were evaluated. Under Alternative 1, NRC would amend its patient release criteria in 10 CFR 35.75 to match the annual public dose limit in Part 20 of 1 millisievert (0.1 rem) TEDE. Alternative 2 would maintain the status quo of using the activity-based release criteria currently found in 10 CFR 35.75. Under Alternative 3, the NRC would revise the release criteria in 10 CFR 35.75 to specify a dose limit of 5 millisieverts (0.5 rem) TEDE

  11. The Canadian experience in performing accuracy checks on administered doses of radiopharmaceuticals

    International Nuclear Information System (INIS)

    Santry, Dallas

    1998-01-01

    A calibration service was introduced in 1986 to assist the Canadian nuclear medicine community in determining more accurately the amount of radioactive material administered to patients for either diagnostic or therapeutic purposes. This aspect of a quality assurance program in nuclear medicine provides an accuracy check on instruments and the technologists using them. The calibration report issued constitutes direct traceability of a facility to a national standards laboratory. Nuclides most frequently calibrated are 99m Tc and 131 I. Others include 67 Ga, 111 In, 123 I, 125 I and 201 Tl. All samples received are analysed for radionuclidic impurities by high-resolution X-ray and gamma-ray spectrometry. Ten years of testing has shown that, except for a few conscientious departments, accuracy checks on radionuclide (dose) calibrators are not a high priority. There are 285 nuclear medicine facilities in Canada and, since there is no legal requirement that the calibrators be checked for accuracy, only 29 have had their instruments checked using this service. Of these, 14 perform annual accuracy checks with NRCC. In this paper, the results of the intercomparisons are described, and quality control problems associated with the use of radionuclide calibrators in nuclear medicine are discussed

  12. The effects of centrally administered fluorocitrate via inhibiting glial cells on working memory in rats

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Although prefrontal and hippocampal neurons are critical for spatial working memory,the function of glial cells in spatial working memory remains uncertain.In this study we investigated the function of glial cells in rats’ working memory.The glial cells of rat brain were inhibited by intracerebroventricular(icv) injection of fluorocitrate(FC).The effects of FC on the glial cells were examined by using electroencephalogram(EEG) recordings and delayed spatial alternation tasks.After icv injection of 10 μL of 0.5 nmol/L or 5 nmol/L FC,the EEG power spectrum recorded from the hippocampus increased,but the power spectrum for the prefrontal cortex did not change,and working memory was unaffected.Following an icv injection of 10 μL of 20 nmol/L FC,the EEG power spectra in both the prefrontal cortex and the hippocampus increased,and working memory improved.The icv injection of 10 μL of 50 nmol/L FC,the EEG power spectra in both the prefrontal cortex and in the hippocampus decreased,and working memory was impaired.These results suggest that spatial working memory is affected by centrally administered FC,but only if there are changes in the EEG power spectrum in the prefrontal cortex.Presumably,the prefrontal glial cells relate to the working memory.

  13. Comparison of self-administered survey questionnaire responses collected using mobile apps versus other methods.

    Science.gov (United States)

    Marcano Belisario, José S; Jamsek, Jan; Huckvale, Kit; O'Donoghue, John; Morrison, Cecily P; Car, Josip

    2015-07-27

    Self-administered survey questionnaires are an important data collection tool in clinical practice, public health research and epidemiology. They are ideal for achieving a wide geographic coverage of the target population, dealing with sensitive topics and are less resource-intensive than other data collection methods. These survey questionnaires can be delivered electronically, which can maximise the scalability and speed of data collection while reducing cost. In recent years, the use of apps running on consumer smart devices (i.e., smartphones and tablets) for this purpose has received considerable attention. However, variation in the mode of delivering a survey questionnaire could affect the quality of the responses collected. To assess the impact that smartphone and tablet apps as a delivery mode have on the quality of survey questionnaire responses compared to any other alternative delivery mode: paper, laptop computer, tablet computer (manufactured before 2007), short message service (SMS) and plastic objects. We searched MEDLINE, EMBASE, PsycINFO, IEEEXplore, Web of Science, CABI: CAB Abstracts, Current Contents Connect, ACM Digital, ERIC, Sociological Abstracts, Health Management Information Consortium, the Campbell Library and CENTRAL. We also searched registers of current and ongoing clinical trials such as ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform. We also searched the grey literature in OpenGrey, Mobile Active and ProQuest Dissertation & Theses. Lastly, we searched Google Scholar and the reference lists of included studies and relevant systematic reviews. We performed all searches up to 12 and 13 April 2015. We included parallel randomised controlled trials (RCTs), crossover trials and paired repeated measures studies that compared the electronic delivery of self-administered survey questionnaires via a smartphone or tablet app with any other delivery mode. We included data obtained from

  14. An Atypical Case of Methemoglobinemia due to Self-Administered Benzocaine

    Directory of Open Access Journals (Sweden)

    Thomas M. Nappe

    2015-01-01

    Full Text Available Acquired methemoglobinemia is an uncommon hemoglobinopathy that results from exposure to oxidizing agents, such as chemicals or medications. Although, as reported in the adult population, it happens most often due to prescribed medication or procedural anesthesia and not due to easily accessed over-the-counter medications, the authors will describe an otherwise healthy male adult with no known medical history and no prescribed medications, who presented to the emergency department reporting generalized weakness, shortness of breath, headache, dizziness, and pale gray skin. In addition, the patient reported that he also had a severe toothache for several days, which he had been self-treating with an over-the-counter oral benzocaine gel. Ultimately, the diagnosis of methemoglobinemia was made by clinical history, physical examination, and the appearance of chocolate-colored blood and arterial blood gas (ABG with cooximetry. After 2 mg/kg of intravenous methylene blue was administered, the patient had complete resolution of all signs and symptoms. This case illustrates that emergency physicians should be keenly aware of the potential of toxic hemoglobinopathy secondary to over-the-counter, nonprescribed medications. Discussion with patients regarding the dangers of inappropriate use of these medicines is imperative, as such warnings are typically not evident on product labels.

  15. The ABCs of LDAP how to install, run, and administer LDAP services

    CERN Document Server

    Voglmaier, Reinhard E

    2004-01-01

    Until now, it has been difficult to find the right source of information on LDAP and directory server implementations: books on the subject are overly product-specific, and a search on the Web results in information overload. The ABCs of LDAP: How to Install, Run, and Administer LDAP Services strikes the right balance, providing a synopsis of LDAP fundamentals without getting wrapped up in one particular implementation.This book is for network and systems administrators who want to begin using LDAP more extensively. It delivers the theoretical background needed to understand how these servers work, resulting in clear, concise examples of implementations in both commercial and OpenLDAP environments.The text is structured so that each chapter can stand on its own, with brief descriptions of terms supplemented by references to more detailed explanations in other chapters. You also benefit from a concise overview of how to design a directory, preparing you to execute directory deployments for email, PKI, DNS, NIS...

  16. Validity and responsiveness of a self-administered foot evaluation questionnaire in rheumatoid arthritis.

    Science.gov (United States)

    Yano, Koichiro; Ikari, Katsunori; Ochi, Kensuke; Ishida, Osamu; Sakuma, Yu; Yoshida, Shinji; Koyama, Takuma; Koenuma, Naoko; Momohara, Shigeki

    2015-05-01

    A self-administered foot evaluation questionnaire (SAFE-Q) was developed by the Japanese Society for Surgery of the Foot (JSSF). The aim of this study is to evaluate the validity and responsiveness of the SAFE-Q in patients with rheumatoid arthritis (RA). In total, 180 patients with RA answered the SAFE-Q. Of 180 patients, 34 answered the SAFE-Q twice, preoperatively and postoperatively, to assess responsiveness. Construct validity was tested by comparing the 5 SAFE-Q subscales and the JSSF standard rating system for the RA foot and ankle scale (JSSF-RA), a Japanese version of the Health Assessment Questionnaire (JHAQ), disease activity score in 28 joints (DAS28), simplified disease activity index (SDAI), and clinical disease activity index (CDAI). Responsiveness was examined by calculating the standardized response mean (SRM) and effect size (ES) 3 months after surgery. There were moderate correlations between the SAFE-Q and the JSSF-RA and JHAQ. Conversely, a low correlation was observed between the SAFE-Q and DAS28, SDAI, and CDAI. The responsiveness was high, with an SRM of 0.9 and ES of 0.7 for pain subscales. SAFE-Q is a useful tool for assessing the foot and ankle in RA patients.

  17. Cyclosporine A administered during reperfusion fails to restore cardioprotection in prediabetic Zucker obese rats in vivo.

    Science.gov (United States)

    Huhn, R; Heinen, A; Hollmann, M W; Schlack, W; Preckel, B; Weber, N C

    2010-12-01

    Hyperglycaemia blocks sevoflurane-induced postconditioning, and cardioprotection in hyperglycaemic myocardium can be restored by inhibition of the mitochondrial permeability transition pore (mPTP). We investigated whether sevoflurane-induced postconditioning is also blocked in the prediabetic heart and if so, whether cardioprotection could be restored by inhibiting mPTP. Zucker lean (ZL) and Zucker obese (ZO) rats were assigned to one of seven groups. Animals underwent 25 min of ischaemia and 120 min of reperfusion. Control (ZL-/ZO Con) animals were not further treated. postconditioning groups (ZL-/ZO Sevo-post) received sevoflurane for 5 min starting 1min prior to the onset of reperfusion. The mPTP inhibitor cyclosporine A (CsA) was administered intravenously in a concentration of 5 (ZO CsA and ZO CsA+Sevo-post) or 10 mg/kg (ZO CsA10+Sevo-post) 5 min before the onset of reperfusion. At the end of reperfusion, infarct sizes were measured by TTC staining. Blood samples were collected to measure plasma levels of insulin, cholesterol and triglycerides. Sevoflurane postconditioning reduced infarct size in ZL rats to 35±12% (pfailed to restore cardioprotection in the prediabetic but normoglycaemic heart of Zucker obese rats in vivo. Copyright © 2009 Elsevier B.V. All rights reserved.

  18. Safety evaluation of intravenously administered mono-thioated aptamer against E-selectin in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Shin-Ae; Tsolmon, Bilegtsaikhan [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States); Mann, Aman P. [Institute of Molecular Medicine, Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030 (United States); Zheng, Wei; Zhao, Lichao; Zhao, Yan Daniel [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States); Volk, David E.; Lokesh, Ganesh L.-R. [Institute of Molecular Medicine, Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030 (United States); Morris, Lynsie; Gupta, Vineet; Razaq, Wajeeha [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States); Rui, Hallgeir [Thomas Jefferson University, 1020 Locust St, Philadelphia, PA 19107 (United States); Suh, K. Stephen [John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ 07601 (United States); Gorenstein, David G. [Institute of Molecular Medicine, Department of NanoMedicine and Biomedical Engineering, University of Texas Health Science Center at Houston, 1825 Hermann Pressler, Houston, TX 77030 (United States); Tanaka, Takemi, E-mail: takemi-tanaka@ouhsc.edu [Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 975 NE, 10th, Oklahoma City, OK 73104 (United States)

    2015-08-15

    The medical applications of aptamers have recently emerged. We developed an antagonistic thioaptamer (ESTA) against E-selectin. Previously, we showed that a single injection of ESTA at a dose of 100 μg inhibits breast cancer metastasis in mice through the functional blockade of E-selectin. In the present study, we evaluated the safety of different doses of intravenously administered ESTA in single-dose acute and repeat-dose subacute studies in ICR mice. Our data indicated that intravenous administration of up to 500 μg ESTA did not result in hematologic abnormality in either study. Additionally, intravenous injection of ESTA did not affect the levels of plasma cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, GM-CSF, IFN-γ, and TNF-α) or complement split products (C3a and C5a) in either study. However, repeated injections of ESTA slightly increased plasma ALT and AST activities, in accordance with the appearance of small necrotic areas in the liver. In conclusion, our data demonstrated that intravenous administration of ESTA does not cause overt hematologic, organs, and immunologic responses under the experimental conditions. - Highlights: • Intravenous administration of ESTA was well tolerated. • ESTA up to 500 μg does not cause hematologic, organs, and immunologic responses. • ESTA-mediated hepatic abnormality was considered minor.

  19. Safety evaluation of intravenously administered mono-thioated aptamer against E-selectin in mice

    International Nuclear Information System (INIS)

    Kang, Shin-Ae; Tsolmon, Bilegtsaikhan; Mann, Aman P.; Zheng, Wei; Zhao, Lichao; Zhao, Yan Daniel; Volk, David E.; Lokesh, Ganesh L.-R.; Morris, Lynsie; Gupta, Vineet; Razaq, Wajeeha; Rui, Hallgeir; Suh, K. Stephen; Gorenstein, David G.; Tanaka, Takemi

    2015-01-01

    The medical applications of aptamers have recently emerged. We developed an antagonistic thioaptamer (ESTA) against E-selectin. Previously, we showed that a single injection of ESTA at a dose of 100 μg inhibits breast cancer metastasis in mice through the functional blockade of E-selectin. In the present study, we evaluated the safety of different doses of intravenously administered ESTA in single-dose acute and repeat-dose subacute studies in ICR mice. Our data indicated that intravenous administration of up to 500 μg ESTA did not result in hematologic abnormality in either study. Additionally, intravenous injection of ESTA did not affect the levels of plasma cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, GM-CSF, IFN-γ, and TNF-α) or complement split products (C3a and C5a) in either study. However, repeated injections of ESTA slightly increased plasma ALT and AST activities, in accordance with the appearance of small necrotic areas in the liver. In conclusion, our data demonstrated that intravenous administration of ESTA does not cause overt hematologic, organs, and immunologic responses under the experimental conditions. - Highlights: • Intravenous administration of ESTA was well tolerated. • ESTA up to 500 μg does not cause hematologic, organs, and immunologic responses. • ESTA-mediated hepatic abnormality was considered minor

  20. Regional cerebral blood flow changes associated with focal electrically administered seizure therapy (FEAST).

    Science.gov (United States)

    Chahine, George; Short, Baron; Spicer, Ken; Schmidt, Matthew; Burns, Carol; Atoui, Mia; George, Mark S; Sackeim, Harold A; Nahas, Ziad

    2014-01-01

    Use of electroconvulsive therapy (ECT) is limited by cognitive disturbance. Focal electrically-administered seizure therapy (FEAST) is designed to initiate focal seizures in the prefrontal cortex. To date, no studies have documented the effects of FEAST on regional cerebral blood flow (rCBF). A 72 year old depressed man underwent three single photon emission computed tomography (SPECT) scans to capture the onset and resolution of seizures triggered with right unilateral FEAST. We used Bioimage Suite for within-subject statistical analyses of perfusion differences ictally and post-ictally compared with the baseline scan. Early ictal increases in regional cerebral blood flow (rCBF) were limited to the right prefrontal cortex. Post-ictally, perfusion was reduced in bilateral frontal and occipital cortices and increased in left motor and precuneus cortex. FEAST appears to triggers focal onsets of seizure activity in the right prefrontal cortex with subsequent generalization. Future studies are needed on a larger sample. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. The custodian administered research extract server: "improving the pipeline" in linked data delivery systems.

    Science.gov (United States)

    Eitelhuber, Tom; Davis, Geoff

    2014-01-01

    At Western Australia's Data Linkage Branch (DLB) the extraction of linked data has become increasingly complex over the past decade and classical methods of data delivery are unsuited to the larger extractions which have become the norm. The Custodian Administered Research Extract Server (CARES) is a fast, accurate and predictable approach to linked data extraction. The Data Linkage Branch (DLB) creates linkage keys within and between datasets. To comply with the separation principal, these keys are sent to applicable data collection agencies for extraction. Routing requests through multiple channels is inefficient and makes it hard to monitor work and predict delivery times. CARES was developed to address these shortcomings and involved ongoing consultation with the Custodians and staff of collections, plus challenges of hardware, programming, governance and security. The introduction of CARES has reduced the workload burden of linked data extractions, while improving the efficiency, stability and predictability of turnaround times. As the scope of a linkage system broadens, challenges in data delivery are inevitable. CARES overcomes multiple obstacles with no sacrifice to the integrity, confidentiality or security of data. CARES is a valuable component of linkage infrastructure that is operable at any scale and adaptable to many data environments.

  2. An Atypical Case of Methemoglobinemia due to Self-Administered Benzocaine.

    Science.gov (United States)

    Nappe, Thomas M; Pacelli, Anthony M; Katz, Kenneth

    2015-01-01

    Acquired methemoglobinemia is an uncommon hemoglobinopathy that results from exposure to oxidizing agents, such as chemicals or medications. Although, as reported in the adult population, it happens most often due to prescribed medication or procedural anesthesia and not due to easily accessed over-the-counter medications, the authors will describe an otherwise healthy male adult with no known medical history and no prescribed medications, who presented to the emergency department reporting generalized weakness, shortness of breath, headache, dizziness, and pale gray skin. In addition, the patient reported that he also had a severe toothache for several days, which he had been self-treating with an over-the-counter oral benzocaine gel. Ultimately, the diagnosis of methemoglobinemia was made by clinical history, physical examination, and the appearance of chocolate-colored blood and arterial blood gas (ABG) with cooximetry. After 2 mg/kg of intravenous methylene blue was administered, the patient had complete resolution of all signs and symptoms. This case illustrates that emergency physicians should be keenly aware of the potential of toxic hemoglobinopathy secondary to over-the-counter, nonprescribed medications. Discussion with patients regarding the dangers of inappropriate use of these medicines is imperative, as such warnings are typically not evident on product labels.

  3. Total body retention of orally administered 47Ca in primary hyperparathyroidism

    International Nuclear Information System (INIS)

    Mallette, L.E.; Sode, J.E.; Marx, S.J.; Georges, L.P.; Aurbach, G.D.

    1975-01-01

    Using a whole-body radiation detector, the total-body retention of 47 Ca 7 days after oral administration of the isotope to patients with various disorders of calcium metabolism was measured. The percent retention of 47 Ca given with 90 mg of unlabeled (carrier) calcium varied with the calcium metabolic status as follows: normals (n = 14), 33--43 percent (mean 38); primary hyperparathyroidism (n = 28), 32--74 percent (mean 52); idiopathic hypercalciuria (n = 9), 34--49 percent (mean 42); and hypercalcemia of other etiology (n = 3), 23--26 percent (mean 25). Almost half (13/28) of those with hyperparathyroidism showed a retention above 55 percent, distinguishing them from subjects with idiopathic hypercalciuria. Retention of 47 Ca correlated poorly with clinical measures of severity of hyperparathyroidism. When isotope was diluted with a smaller amount of carrier calcium (20 mg), retention was increased in normals (n = 5) to 46--54 percent (mean 50) and in hyperparathyroidism (n = 5) to 64--87 percent (mean 73). After surgical cure of hyperparathyroidism retention of isotope returned toward normal in 5 of 7 subjects. Whole-body retention of orally administered 47 Ca may prove useful in detecting hyperparathyroidism in subjects with mild hypercalcemia or hypercalciuria. (U.S.)

  4. Improving the prediction of the brain disposition for orally administered drugs using BDDCS

    DEFF Research Database (Denmark)

    Broccatelli, Fabio; Larregieu, Caroline A.; Cruciani, Gabriele

    2012-01-01

    outcome. Passive permeability and P-glycoprotein (Pgp, ABCB1) efflux have been successfully recognized to impact xenobiotic extrusion from the brain, as Pgp is known to play a role in limiting the BBB penetration of oral drugs in humans. However, these two properties alone fail to explain the BBB...... penetration for a significant number of marketed central nervous system (CNS) agents. The Biopharmaceutics Drug Disposition Classification System (BDDCS) has proved useful in predicting drug disposition in the human body, particularly in the liver and intestine. Here we discuss the value of using BDDCS...

  5. The reactivation effect of pralidoxime in human blood on parathion and paraoxon–induced cholinesterase inhibition

    Directory of Open Access Journals (Sweden)

    Mahvash Jafari

    2006-03-01

    Full Text Available In this investigation the reactivation of cholinesterases by pralidoxime in parathion and paraoxon intoxication in plasma and erythrocytes were studied. For this purpose, human plasma and erythrocytes were incubated with various concentrations of parathion (0.1-10 µM and paraoxon (0.03-0.3 µM at 37 oC for 10 min. Then, pralidoxime (10-300 µM was added to the samples and incubated for 10 min before cholinesterases assay. The results showed that effects of parathion and paraoxon were dose dependent. These agents inhibited more than 85% of butyrylcholinesterase (BChE and acetylcholinesterase (AChE activity and the inhibitory effect of paraoxon was 10 times more than parathion. BChE activity was significantly higher than the control at 100 µM of pralidoxime and it reduced inhibitory effects of parathion to less than 50% and of paraoxon to 42% of control. When pralidoxime (10 µM was added to erythrocytes, the inhibitory effects of two organophosphates were reduced to less than 15%. At higher concentrations of pralidoxime (>100 µM, both BChE and AChE activities were inhibited.

  6. Resorcinol-, catechol- and saligenin-based bronchodilating β2-agonists as inhibitors of human cholinesterase activity.

    Science.gov (United States)

    Bosak, Anita; Knežević, Anamarija; Gazić Smilović, Ivana; Šinko, Goran; Kovarik, Zrinka

    2017-12-01

    We investigated the influence of bronchodilating β2-agonists on the activity of human acetylcholinesterase (AChE) and usual, atypical and fluoride-resistant butyrylcholinesterase (BChE). We determined the inhibition potency of racemate and enantiomers of fenoterol as a resorcinol derivative, isoetharine and epinephrine as catechol derivatives and salbutamol and salmeterol as saligenin derivatives. All of the tested compounds reversibly inhibited cholinesterases with K i constants ranging from 9.4 μM to 6.4 mM and had the highest inhibition potency towards usual BChE, but generally none of the cholinesterases displayed any stereoselectivity. Kinetic and docking results revealed that the inhibition potency of the studied compounds could be related to the size of the hydroxyaminoethyl chain on the benzene ring. The additional π-π interaction of salmeterol's benzene ring and Trp286 and hydrogen bond with His447 probably enhanced inhibition by salmeterol which was singled out as the most potent inhibitor of all the cholinesterases.

  7. Exogenous insulin does not increase muscle protein synthesis rate when administered systemically: a systematic review

    NARCIS (Netherlands)

    Trommelen, J.; Groen, B.; Hamer, H.M.; Groot, de C.P.G.M.; Loon, van L.J.C.

    2015-01-01

    Background Though it is well appreciated that insulin plays an important role in the regulation of muscle protein metabolism, there is much discrepancy in the literature on the capacity of exogenous insulin administration to increase muscle protein synthesis rates in vivo in humans. Objective To

  8. Preclinical evaluation of intravenously administered 111In-and 90Y-labeled B72.3 immunoconjugate (GYK-DTPA) in beagle dogs

    International Nuclear Information System (INIS)

    Quadri, S.M.; Vriesendorp, H.M.; Yi Shao; Blum, J.E.; Leichner, P.K.; Williams, J.R.

    1993-01-01

    B72.3, a monoclonal antibody with reactivity against human adenocarcinomas was obtained from the Cytogen Corporation in the form of an immunoconjugate coupled with linker-chelator GYK-DTPA by using proprietary carbohydrate directed site specific chemistry. The immunoconjugate was radiolabeled with indium-111 or yttrium-90. A preclinical analysis was performed in 10 normal beagle dogs. The pharmacokinetics of intravenously administered indium- and yttrium-labeled immunoconjugates were compared serially in blood, bone marrow and urine samples. Compared to 90 Y less of the 111 In label ended up in urine and more was found in blood and bone marrow. Indium-labeled B72.3 GYK-DTPA had relatively higher uptake in most glandular tissues than 111 In-labeled antiferritin immunoconjugate. Bone marrow toxicity was the dose limiting side effect after intravenous infusion of 90 Y-labeled B72.3 GYK-DTPA. Toxicity was also observed in the liver but not in other organ systems. Recently other investigators obtained similar results with these immunoconjugates in human patients. A preclinical pharmacokinetic analysis of radioimmunoconjugates in beagle dogs provided useful information regarding bone marrow toxicity, liver toxicity and in vivo instability of the immunoconjugate. Data suggest that for future trials in human patients, a more stable chelated immunoconjugate for yttrium is needed to achieve less liver uptake and a better correlation with the 111 In-labeled product than the 90 Y-labeled B72.3 GYK-DTPA used in this investigation. (Author)

  9. Differential effects of orally versus parenterally administered qinghaosu derivative artemether in dogs.

    Science.gov (United States)

    Classen, W; Altmann, B; Gretener, P; Souppart, C; Skelton-Stroud, P; Krinke, G

    1999-11-01

    Artemether (AM) is an antimalarial drug derived from artemisinin (Qinghaosu), an extract of the herb Artemisia annua L., sweet wormwood. Its antiparasitic effect is that of a schizontocide and is explained by rapid uptake by parasitized erythrocytes and interaction with a component of hemoglobin degradation resulting in formation of free radicals. It has been shown to exhibit a high clinical cure rate. Previous animal safety studies with Qinghaosu derivatives revealed dose-dependent neurotoxicity with movement disturbances and neuropathic changes in the hindbrain of intramuscularly treated dogs, rats and monkeys. Such effects have not been seen in man. The objective of our present studies was to compare the effects of high levels of AM administered to dogs p.o. versus i.m. In a pilot study 20 mg/kg/day of AM was given i.m. to groups of 3 male Beagle dogs for 5 and 30 days, respectively. Clinical signs of neurotoxicity were noted in some individual dogs from test day 23 on. One dog had to be sacrificed pre-term. Hematologic findings indicated a hypochromic, microcytic anemia. Microscopic examination demonstrated neuropathic changes only at 30 days, but not at 5 days. The animals had neuronal and secondary axonal damage, most prominent in the cerebellar roof, pontine and vestibular nuclei, and in the raphe/paralemniscal region. The affected neurons showed loss of Nissl substance, cytoplasmic eosinophilia, shrinkage of the nucleus and in advanced stages scavenging by microglia. In a subsequent experiment, AM was administered to groups of 4 male and 4 female dogs, respectively, at 8 daily doses of 0, 20, 40 and 80 mg/kg i.m., or 0, 50, 150 and 600 mg/kg p.o. Neurologic signs were seen at high i.m. doses only. In most animals they were inconspicuous and consisted of reduced activity with convulsions seen in single dogs shortly before death. Neuronal damage occurred in all animals at 40 and 80 mg/kg following i.m. treatment. At 20 mg/kg minimal effects occurred in 5

  10. Bupivacaine administered intrathecally versus rectally in the management of intractable rectal cancer pain in palliative care

    Directory of Open Access Journals (Sweden)

    Zaporowska-Stachowiak I

    2014-10-01

    Full Text Available Iwona Zaporowska-Stachowiak,1,2 Grzegorz Kowalski,3 Jacek Łuczak,2 Katarzyna Kosicka,4 Aleksandra Kotlinska-Lemieszek,3 Maciej Sopata,3 Franciszek Główka4 1Chair and Department of Pharmacology, Poznan University of Medical Sciences, Poznan, Poland; 2Palliative Medicine In-patient Unit, University Hospital of Lord's Transfiguration, Poznan University of Medical Sciences, Poznan, Poland; 3Palliative Medicine Chair and Department, Poznan University of Medical Sciences, Poznan, Poland; 4Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Poznan, Poland Background: Unacceptable adverse effects, contraindications to and/or ineffectiveness of World Health Organization step III "pain ladder" drugs causes needless suffering among a population of cancer patients. Successful management of severe cancer pain may require invasive treatment. However, a patient's refusal of an invasive procedure necessitates that clinicians consider alternative options. Objective: Intrathecal bupivacaine delivery as a viable treatment of intractable pain is well documented. There are no data on rectal bupivacaine use in cancer patients or in the treatment of cancer tenesmoid pain. This study aims to demonstrate that bupivacaine administered rectally could be a step in between the current treatment options for intractable cancer pain (conventional/conservative analgesia or invasive procedures, and to evaluate the effect of the mode of administration (intrathecal versus rectal on the bupivacaine plasma concentration.Cases: We present two Caucasian, elderly inpatients admitted to hospice due to intractable rectal/tenesmoid pain. The first case is a female with vulvar cancer, and malignant infiltration of the rectum/vagina. Bupivacaine was used intrathecally (0.25–0.5%, 1–2 mL every 6 hours. The second case is a female with ovarian cancer and malignant rectal infiltration. Bupivacaine was adminstered rectally (0.05–0.1%, 100 m

  11. An estimate of the cost of administering intravenous biological agents in Spanish day hospitals

    Directory of Open Access Journals (Sweden)

    Nolla JM

    2017-03-01

    Full Text Available Joan Miquel Nolla,1 Esperanza Martín,2 Pilar Llamas,3 Javier Manero,4 Arturo Rodríguez de la Serna,5 Manuel Francisco Fernández-Miera,6 Mercedes Rodríguez,6 José Manuel López,7 Alexandra Ivanova,8 Belén Aragón9 1Rheumatology Department, IDIBELL-Hospital Universitari de Bellvitge, Barcelona, 2Hospital Universitario de Getafe, Madrid, 3Hospital Universitario Fundación Jiménez Díaz, Madrid, 4Hospital Universitario Miguel Servet, Zaragoza, 5Hospital de la Santa Creu i Sant Pau, Barcelona, 6Hospital Universitario Marqués de Valdecilla, Santander, 7Hospital Universitario Virgen del Rocío, Sevilla, 8Max Weber Institute, Madrid, 9MSD, Madrid, Spain Objective: To estimate the unit costs of administering intravenous (IV biological agents in day hospitals (DHs in the Spanish National Health System.Patients and methods: Data were obtained from 188 patients with rheumatoid arthritis, collected from nine DHs, receiving one of the following IV therapies: infliximab (n=48, rituximab (n=38, abatacept (n=41, or tocilizumab (n=61. The fieldwork was carried out between March 2013 and March 2014. The following three groups of costs were considered: 1 structural costs, 2 material costs, and 3 staff costs. Staff costs were considered a fixed cost and were estimated according to the DH theoretical level of activity, which includes, as well as personal care of each patient, the DH general activities (complete imputation method, CIM. In addition, an alternative calculation was performed, in which the staff costs were considered a variable cost imputed according to the time spent on direct care (partial imputation method, PIM. All costs were expressed in euros for the reference year 2014.Results: The average total cost was €146.12 per infusion (standard deviation [SD] ±87.11; CIM and €29.70 per infusion (SD ±11.42; PIM. The structure-related costs per infusion varied between €2.23 and €62.35 per patient and DH; the cost of consumables oscillated

  12. Induction of salivary polypeptides associated with parotid hypertrophy by gallotannins administered topically into the mouse mouth.

    Science.gov (United States)

    Gho, Francesca; Peña-Neira, Alvaro; López-Solís, Remigio O

    2007-02-01

    Isoproterenol-induced salivary polypeptides (IISP), a group of proline-rich proteins synthesized by mouse parotids, have been considered as markers for isoproterenol-induced parotid hypertrophy. Rodents fed diets containing high-tannin cereals (sorghum), also develop parotid hypertrophy. To test whether tannins are directly involved in provoking sialotrophic growth, we studied the effect of intraperitoneal and topical oral administrations of tannic acid (TA) on the induction of IISP polypeptides in endogamic mice (A/Snell). TA was characterized by HPLC chromatography and spectral analysis and shown to be composed solely of gallotannins, a complex family of glucose and gallic acid esters. IISP polypeptides were monitored in saliva by SDS-polyacrylamide gel electrophoresis during 36 h after ending TA stimulation. Single daily intraperitoneal administrations of TA for 3 consecutive days (0.033 mg/g bw/day), at variance of parallel administrations of isoproterenol (0.042 mg/g bw/day) failed to induce IISP polypeptides. However, repeated topical applications of TA into the mouse mouths (1.21 mg/g bw divided into three equal doses given at 4-h intervals within a single day) resulted in unequivocal induction of IISP polypeptides. That response was clearly intensified by increasing the stimulation frequency to eight equivalent doses given at 1.5-h intervals within a single day (corresponding to 3.23 mg/g bw) and even further by repeating this protocol for 3 days. Under these productive schemes of stimulations by TA, electrophoretic fractionation of parotid homogenates showed new polypeptide bands migrating in parallel to salivary IISP. These results suggest that topically administered gallotannins are effective inducers of trophic growth in mouse parotids.

  13. Market surveillance panel monitoring report on the IMO-administered electricity markets : Executive summary

    International Nuclear Information System (INIS)

    2002-01-01

    The electricity market in Ontario was opened on May 1, 2002. This document provides the executive summary for the first monitoring report prepared by the Market Surveillance Panel covering the period May to August 2002. In the introductory chapter of the main report, explanations are provided on why competition, when effective, benefits consumers, as well as touching on the conditions for the design of an effective competitive electricity market with special emphasis on the electricity market in Ontario and its operations. For the period under review, the report presents a description and analysis of the activities and operations of the Independent Electricity Market Operator (IMO)-administered markets (focus on energy markets). Rising costs for hydroelectric power and very high temperatures combined in July and August resulting in record levels of demand. It became apparent that the province relies on imports to satisfy demand. The figures reveal that reliability in July and August depended on imports 21 per cent of the time. A serious shortage of generating capacity exists in Ontario and steps to rectify the situation should be initiated to ensure reliability of electricity supply for next summer. Prospective entrants in the electricity market in Ontario may not be receiving clear, credible and consistent signals. Effective use of existing or potential transmission capacity may not always be made by the system. The lowering of consumption by consumers is difficult since consumers are not properly equipped, resulting in their lack of power to discipline price increases from suppliers. The future evolution of the market must be planned and measures implemented to enhance the effectiveness of competition. The incentives effects for some aspects of the market design do not completely satisfy the Panel

  14. Distribution of intraarterially administered papaverine in endovascular treatment of delayed cerebral vasospasm

    Energy Technology Data Exchange (ETDEWEB)

    Touho, Hajime; Fukuoka, Norihiko; Karasawa, Jun [Osaka Neurological Inst., Toyonaka (Japan)

    1997-02-01

    The distribution of selectively administered papaverine was determined in nine patients with delayed cerebral vasospasm in the territories of the anterior (ACA) and/or middle cerebral arteries (MCA) secondary to aneurysmal subarachnoid hemorrhage by simultaneous infusion with technetium-99m-hexamethyl-propyleneamine oxime ({sup 99m}Tc-HMPAO). Four of the nine patients had a ruptured anterior communicating artery aneurysm, four had an internal carotid artery aneurysm, and the remaining one had a MCA aneurysm. Trapping of anterior communicating artery was carried out in one case and clipping of aneurysms in other eight cases. Neurological deterioration with hemiparesis, paraparesis, and/or somnolence appeared between postsurgical days 8 and 13 due to delayed cerebral vasospasm in all patients. Intraarterial infusion of 40 mg of papaverine containing 37 MBq of {sup 99m}Tc-HMPAO was performed from the C{sub 1} segment in seven of the nine patients and from the C{sub 4} segment in the other two patients. {sup 99m}Tc-HMPAO was distributed in the territories of the ACA and MCA in the two patients who were treated with intraarterial infusion of papaverine from the C{sub 4} segment, but was distributed only to the territory of the ACA in four patients who were treated with intraarterial infusion of papaverine from the C{sub 1} segment at 1 ml/min. In contrast, {sup 99m}Tc-HMPAO was distributed in the territories of the ACA and MCA in the three patients who were treated with papaverine from the C{sub 1} segment at 2 ml/min, although most {sup 99m}Tc-HMPAO was distributed in the territory of the ACA. Vasospasm of the ACA can be treated by intraarterial infusion of papaverine from the C{sub 1} segment at 1 ml/min when selective catheterization to the ACA is difficult to perform. (author)

  15. Pharmacokinetics of Tenofovir Alafenamide When Co-administered With Other HIV Antiretrovirals.

    Science.gov (United States)

    Begley, Rebecca; Das, Moupali; Zhong, Lijie; Ling, John; Kearney, Brian P; Custodio, Joseph M

    2018-04-10

    Tenofovir alafenamide (TAF), a prodrug of the nucleotide analogue tenofovir (TFV), is an antiretroviral (ARV) agent approved either as a complete regimen (elvitegravir/cobicistat/emtricitabine (F)/tenofovir alafenamide (TAF), rilpivirine/F/TAF, bictegravir/F/TAF), or for use with other ARVs (F/TAF), for treatment of HIV. TAF is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters. Disposition of TAF may be altered by co-medications that can inhibit or induce P-gp or BCRP transporters. The effects of ARVs on the pharmacokinetics (PK) of TAF were evaluated in 3 studies. Healthy participants received TAF administered alone or with rilpivirine (RPV) in study 1; with dolutegravir (DTG), ritonavir boosted atazanavir (ATV+RTV), lopinavir (LPV/RTV), or darunavir (DRV+RTV) in study 2; and with the pharmacokinetic enhancer cobicistat (COBI), or efavirenz (EFV) in study 3. Across the three studies, 98 participants received treatment with TAF and a coadministered agent (n=10-34/cohort). All study treatments were well tolerated. TAF and TFV exposures were unaffected following co-administration with RPV and DTG. Co-administration with Pgp/BCRP inhibitors such as COBI or PI based regimens (ATV+RTV, LPV/r or DRV+RTV) resulted in a range of 6% to 183% increases in TAF and 105% to 316% increases in TFV exposure, while co-administration with a Pgp inducer, EFV, resulted in a 15% to 24% decrease in TAF and TFV exposure. Evaluation of the drug interaction between TAF and other commonly prescribed boosted and unboosted ARVs provides characterization of the susceptibility of TAF and/or TFV PK to inhibitors or inducers of Pgp/BCRP transporters.

  16. The antihypertensive effect of orally administered nifedipine-loaded nanoparticles in spontaneously hypertensive rats.

    Science.gov (United States)

    Kim, Y I; Fluckiger, L; Hoffman, M; Lartaud-Idjouadiene, I; Atkinson, J; Maincent, P

    1997-02-01

    1. The therapeutic use of nifedipine is limited by the rapidity of the onset of its action and its short biological half-life. In order to produce a form devoid of these disadvantages we made nanoparticles of nifedipine from three different polymers, poly-epsilon-caprolactone (PCL), polylactic and glycolic acid (1:1) copolymers (PLAGA), and Eudragit RL/RS (Eudragit). Nifedipine in polyethylene glycol 400 (PEG) solution was used as a control. 2. The average diameters of the nanoparticles ranged from 0.12 to 0.21 micron; the encapsulation ratio was 82% to 88%. 3. In spontaneously hypertensive rats (SHR), the initial rapid fall in systolic arterial blood pressure following oral administration of nifedipine in PEG solution (from 193 +/- 3 to 102 +/- 2 mmHg) was not seen following administration of the same dose in Eudragit nanoparticles (from 189 +/- 2 to 156 +/- 2 mmHg); with PCL and PLAGA nanoparticles the initial fall in blood pressure was significantly reduced (nadirs PCL 124 +/- 2 and PLAGA 113 +/- 2 mmHg). Ten hours following administration, blood pressure in rats administered the nifedipine/PEG preparation had returned to normal (183 +/- 3 mmHg) whereas that of animals given nifedipine in nanoparticles (PCL 170 +/- 3, PLAGA 168 +/- 2, Eudragit 160 +/- 3 mmHg) was still significantly reduced. 4. All of the nanoparticle dosage forms decreased Cmax and increased Tmax and the mean residence time (MRT) values. Relative bioavailability was significantly increased with Eudragit nanoparticles compared to the nifedipine/PEG solution. 5. There was an inverse linear correlation between the fall in blood pressure and plasma nifedipine concentration with all preparations. 6. The nanoparticle nifedipine preparations represent sustained release forms with increased bioavailability, a less pronounced initial antihypertensive effect and a long-lasting action.

  17. Administer and collect medical questionnaires with Google documents: a simple, safe, and free system.

    Science.gov (United States)

    Rayhan, Rakib U; Zheng, Yin; Uddin, Ebsan; Timbol, Christian; Adewuyi, Oluwatoyin; Baraniuk, James N

    2013-01-01

    Questionnaires are an invaluable resource for clinical trials. They serve to estimate disease burden and clinical parameters associated with a particular study. However, current researchers are tackling budget constraints, loss of funding opportunities, and rise of research associated fees. We aimed at exploring alternative avenues taking advantage of the free Google docs software for questionnaire administration. This presents an opportunity to reduce costs while simultaneously increasing efficiency and data fidelity. Google documents were used as a platform to create online questionnaires that were automatically hosted via a unique URL. Password protected access to the URL link and a unique study ID gave patients around the clock access from anywhere in the world. Unique study ID ensured confidentially of all self-reported data. Patient responses were secured using a "Cloud" database where the data was automatically sorted, scaled and scored by custom Excel formulas. Researchers downloaded real-time questionnaire responses in multiple formats (e.g. excel) which was then analyzed with a statistical software of choice. This simple workflow provided instant questionnaire scores that eliminated the use for paper-based responses and subsequent manual entry of data. Ease of access to online questionnaires provided convenience to patients leading to better response rates and increase in data fidelity. The system also allowed for real time monitoring of patient's progress on completing questionnaires. Online questionnaires had 100% completion rate compared to paper-based questionnaires. Google docs can serve as an efficient and free platform to administer questionnaires to a clinical population without sacrificing quality, security, and fidelity of data.

  18. Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs.

    Science.gov (United States)

    Larson, Jeanne C; Allstadt, Sara D; Fan, Timothy M; Khanna, Chand; Lunghofer, Paul J; Hansen, Ryan J; Gustafson, Daniel L; Legendre, Alfred M; Galyon, Gina D; LeBlanc, Amy K; Martin-Jimenez, Tomas

    2016-01-01

    To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. 5 healthy purpose-bred hounds. The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received rapamycin (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and noncompartmental analyses. Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in nanograms per milliliter. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, need to be determined.

  19. Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs: A pilot study

    Science.gov (United States)

    Larson, Jeanne C.; Allstadt, Sara D.; Fan, Timothy M.; Khanna, Chand; Lunghofer, Paul J.; Hansen, Ryan J.; Gustafson, Daniel L.; Legendre, Alfred M.; Galyon, Gina D.; LeBlanc, Amy K.; Martin-Jimenez, Tomas

    2017-01-01

    Objective To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. Animals 5 healthy purpose-bred hounds. Procedures The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and non-compartmental analyses. Results Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Conclusions and Clinical Relevance Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in ng/mL. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, needs to be determined. PMID:26709938

  20. Corticosteroid effects on ventilator-induced diaphragm dysfunction in anesthetized rats depend on the dose administered

    Directory of Open Access Journals (Sweden)

    Decramer Marc

    2010-12-01

    Full Text Available Abstract Background High dose of corticosteroids has been previously shown to protect against controlled mechanical ventilation (CMV-induced diaphragmatic dysfunction while inhibiting calpain activation. Because literature suggests that the calpain inhibiting effect of corticosteroid depends on the dose administered, we determined whether lower doses of corticosteroids would also provide protection of the diaphragm during CMV. This may be important for patients undergoing mechanical ventilation and receiving corticosteroids. Methods Rats were assigned to controls or to 24 hours of CMV while being treated at the start of mechanical ventilation with a single intramuscular administration of either saline, or 5 mg/kg (low MP or 30 mg/kg (high MP of methylprednisolone. Results Diaphragmatic force was decreased after CMV and this was exacerbated in the low MP group while high MP rescued this diaphragmatic dysfunction. Atrophy was more severe in the low MP group than after CMV while no atrophy was observed in the high MP group. A significant and similar increase in calpain activity was observed in both the low MP and CMV groups whereas the high dose prevented calpain activation. Expression of calpastatin, the endogenous inhibitor of calpain, was decreased in the CMV and low MP groups but its level was preserved to controls in the high MP group. Caspase-3 activity increased in all CMV groups but to a lesser extent in the low and high MP groups. The 20S proteasome activity was increased in CMV only. Conclusions Administration of 30 mg/kg methylprednisolone during CMV protected against CMV-induced diaphragm dysfunction while 5 mg/kg was more deleterious. The protective effect is due mainly to an inhibition of the calpain system through preservation of calpastatin levels and to a lesser extent to a caspase-3 inhibition.

  1. Why did the FDA approve efavirenz 800 mg when co-administered with rifampin?

    Science.gov (United States)

    Liu, Jiang; Chan-Tack, Kirk M; Jadhav, Pravin; Seo, Shirley; Robertson, Sarah M; Kraft, Jeffrey; Singer, Mary E; Struble, Kimberly A; Arya, Vikram

    2014-06-01

    Literature reports regarding the efficacy of efavirenz (EFV) 600 mg with rifampin (RIF) are not consistent. Evaluation of a drug-drug interaction (DDI) study and supportive semi-mechanistic population pharmacokinetic (PK) analyses were undertaken to help delineate this issue. DDI study and supportive semi-mechanistic population PK analyses were provided by BMS. Population PK analysis was based on six studies with intensive EFV PK sampling. An ACTG study with sparse PK sampling was used for model evaluation. Simulations compared EFV exposure at various doses in combination with RIF to EFV exposures at 600 mg once daily (QD). Effects of CYP2B6 genotypes on the magnitude of EFV-RIF interaction were also explored. In DDI study, co-administering EFV 600 mg QD and RIF reduced mean EFV exposure by ~ 30%. Population PK model provided acceptable predictive performance of central tendency and variability for EFV C0, Cmax, and AUC. Simulations predicted that increasing EFV to 800 mg QD with RIF would result in EFV AUC and Cmax similar to EFV 600 mg QD alone. EFV AUC and Cmax were ~ 2 times higher in subjects with reduced function CYP2B6 genotypes. However, the RIF effect was consistent across all genotypes. EFV dose adjustment to 800 mg QD did not increase the risk of overexposure compared to 600 mg EFV QD within each genotype. Dose adjustment based on matching systemic exposure was recommended to mitigate the potential for sub-therapeutic EFV exposures. Our review did not reveal any safety concerns in subjects receiving EFV 800 mg QD with RIF.

  2. Depression screening using the Patient Health Questionnaire-9 administered on a touch screen computer.

    Science.gov (United States)

    Fann, Jesse R; Berry, Donna L; Wolpin, Seth; Austin-Seymour, Mary; Bush, Nigel; Halpenny, Barbara; Lober, William B; McCorkle, Ruth

    2009-01-01

    To (1) evaluate the feasibility of touch screen depression screening in cancer patients using the Patient Health Questionnaire-9 (PHQ-9), (2) evaluate the construct validity of the PHQ-9 using the touch screen modality, and (3) examine the prevalence and severity of depression using this screening modality. The PHQ-9 was placed in a web-based survey within a study of the clinical impact of computerized symptom and quality of life screening. Patients in medical oncology, radiation oncology, and hematopoietic stem cell transplantation (HSCT) clinics used the program on a touch screen computer in waiting rooms prior to therapy (T1) and during therapy (T2). Responses of depressed mood or anhedonia (PHQ-2 cardinal depression symptoms) triggered additional items. PHQ-9 scores were provided to the oncology team in real time. Among 342 patients enrolled, 33 (9.6%) at T1 and 69 (20.2%) at T2 triggered the full PHQ-9 by endorsing at least one cardinal symptom. Feasibility was high, with at least 97% completing the PHQ-2 and at least 96% completing the PHQ-9 when triggered and a mean completion time of about 2 min. The PHQ-9 had good construct validity. Medical oncology patients had the highest percent of positive screens (12.9%) at T1, while HSCT patients had the highest percent (30.5%) at T2. Using this method, 21 (6.1%) at T1 and 54 (15.8%) at T2 of the total sample had moderate to severe depression. The PHQ-9 administered on a touch screen computer is feasible and provides valid depression data in a diverse cancer population. (c) 2008 John Wiley & Sons, Ltd.

  3. Anaesthetic effects of alfaxalone administered intraperitoneally alone or combined with dexmedetomidine and fentanyl in the rat.

    Science.gov (United States)

    Arenillas, Mario; Gomez de Segura, Ignacio A

    2018-01-01

    Alfaxalone is a neuroactive steroid used as a general anaesthetic in several species including dogs, cats, rabbits and ferrets. It has a wide margin of safety and a similar anaesthetic profile to propofol. To increase its aqueous solubility, a new formulation with cyclodextrins has been marketed recently. The objective of this study was to evaluate the anaesthetic effect of several doses of alfaxalone alone, considering differences between sexes, and alfaxalone combined with dexmedetomidine and fentanyl in the rat administered by the intraperitoneal route. A total of 40 Sprague Dawley rats, involved in three studies, were used. Firstly, 25, 35 and 45 mg kg -1 of alfaxalone alone were tested. In a second study, alfaxalone (25 mg kg -1 , females; 75 mg kg -1 , males) was combined with dexmedetomidine (0.05 mg kg -1 ). Finally, alfaxalone (20 mg kg -1 , females; 60 mg kg -1 , males) was combined with dexmedetomidine (0.05 mg kg -1 ) and fentanyl (0.1 mg kg -1 ). Times of onset and duration of anaesthesia, and analgesia, deemed as losing of withdrawal pedal reflex, were recorded. Alfaxalone alone produced a 2 - to 3-fold longer time of anaesthesia in females, although surgical anaesthesia was not achieved in either sex. The addition of dexmedetomidine and fentanyl to alfaxalone produced a similar time of analgesia as well as increased time of anaesthesia in both sexes. In conclusion, alfaxalone produces light anaesthesia in rats, and males required a higher dose. The combination with other sedatives or analgesics, such as dexmedetomidine or fentanyl, allows a more prolonged anaesthesia with analgesic effects, potentially suitable for invasive procedures.

  4. Does training people to administer take-home naloxone increase their knowledge? Evidence from Australian programs.

    Science.gov (United States)

    Dietze, Paul M; Draper, Bridget; Olsen, Anna; Chronister, Karen J; van Beek, Ingrid; Lintzeris, Nicholas; Dwyer, Robyn; Nelson, Marina; Lenton, Simon

    2018-02-22

    Take-home naloxone (THN) programs have been operating in Australia since 2012 in a variety of settings. We examine whether THN programs were effective in increasing knowledge about opioid overdose and appropriate responses in program participants. Data were obtained from pre- and post-training questionnaires administered as part of the early evaluations of THN naloxone programs operated in Sydney (n = 67), Melbourne (n = 280), Perth (n = 153) and Canberra (n = 183). Pooled data from comparable items, analysed in the domains specified in previously-developed evaluation scales, were compared using repeated-measures analysis of variance and random effects logistic regression. Results pre- and post-training were compared as well as results across sites. High levels of knowledge about overdose risks and signs and appropriate actions to take were observed at baseline and this generally improved over time. No substantial differences were identified across cities. Knowledge also increased with participant age but the improvements over time were similar in each age group. There were small differences by participant gender with knowledge generally higher among females. THN programs are effective in improving knowledge related to overdose response. Major improvements in knowledge were limited to overdose recognition and effect of naloxone suggesting that education may best be focused on overdose signs and the use of naloxone among populations accessed through these programs. A focus on younger people also appears warranted. Further work is needed to understand the impact of training and knowledge on actual behaviours around overdose events. © 2018 Australasian Professional Society on Alcohol and other Drugs.

  5. Administer and collect medical questionnaires with Google documents: a simple, safe, and free system

    Directory of Open Access Journals (Sweden)

    Rakib Uddin RAYHAN

    2013-09-01

    Full Text Available Aim: Questionnaires are an invaluable resource for clinical trials. They serve to estimate disease burden and clinical parameters associated with a particular study. However, current researchers are tackling budget constraints, loss of funding opportunities, and rise of research associated fees. We aimed at exploring alternative avenues taking advantage of the free Google docs software for questionnaire administration. This presents an opportunity to reduce costs while simultaneously increasing efficiency and data fidelity. Material and Methods: Google documents were used as a platform to create online questionnaires that were automatically hosted via a unique URL. Password protected access to the URL link and a unique study ID gave patients around the clock access from anywhere in the world. Unique study ID ensured confidentially of all self-reported data. Patient responses were secured using a “Cloud” database where the data was automatically sorted, scaled and scored by custom Excel formulas. Researchers downloaded real-time questionnaire responses in multiple formats (e.g. excel which was then analyzed with a statistical software of choice. Results: This simple workflow provided instant questionnaire scores that eliminated the use for paper-based responses and subsequent manual entry of data. Ease of access to online questionnaires provided convenience to patients leading to better response rates and increase in data fidelity. The system also allowed for real time monitoring of patient’s progress on completing questionnaires. Online questionnaires had 100% completion rate compared to paper-based questionnaires. Conclusions: Google docs can serve as an efficient and free platform to administer questionnaires to a clinical population without sacrificing quality, security, and fidelity of data.

  6. Intranasally administered mesenchymal stem cells promote a regenerative niche for repair of neonatal ischemic brain injury.

    Science.gov (United States)

    Donega, Vanessa; Nijboer, Cora H; van Tilborg, Geralda; Dijkhuizen, Rick M; Kavelaars, Annemieke; Heijnen, Cobi J

    2014-11-01

    Previous work from our group has shown that intranasal MSC-treatment decreases lesion volume and improves motor and cognitive behavior after hypoxic-ischemic (HI) brain damage in neonatal mice. Our aim was to determine the kinetics of MSC migration after intranasal administration, and the early effects of MSCs on neurogenic processes and gliosis at the lesion site. HI brain injury was induced in 9-day-old mice and MSCs were administered intranasally at 10days post-HI. The kinetics of MSC migration were investigated by immunofluorescence and MRI analysis. BDNF and NGF gene expression was determined by qPCR analysis following MSC co-culture with HI brain extract. Nestin, Doublecortin, NeuN, GFAP, Iba-1 and M1/M2 phenotypic expression was assessed over time. MRI and immunohistochemistry analyses showed that MSCs reach the lesion site already within 2h after intranasal administration. At 12h after administration the number of MSCs at the lesion site peaks and decreases significantly at 72h. The number of DCX(+) cells increased 1 to 3days after MSC administration in the SVZ. At the lesion, GFAP(+)/nestin(+) and DCX(+) expression increased 3 to 5days after MSC-treatment. The number of NeuN(+) cells increased within 5days, leading to a dramatic regeneration of the somatosensory cortex and hippocampus at 18days after intranasal MSC administration. Interestingly, MSCs expressed significantly more BDNF gene when exposed to HI brain extract in vitro. Furthermore, MSC-treatment resulted in the resolution of the glial scar surrounding the lesion, represented by a decrease in reactive astrocytes and microglia and polarization of microglia towards the M2 phenotype. In view of the current lack of therapeutic strategies, we propose that intranasal MSC administration is a powerful therapeutic option through its functional repair of the lesion represented by regeneration of the cortical and hippocampal structure and decrease of gliosis. Copyright © 2014. Published by Elsevier Inc.

  7. In vitro viability effects on apheresis and buffy-coat derived platelets administered through infusion pumps

    Directory of Open Access Journals (Sweden)

    Sandgren P

    2014-12-01

    Full Text Available Per Sandgren,1,2 Veronica Berggren,3 Carl Westling,1,2 Viveka Stiller1 1Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, 2Department of Laboratory Medicine, Karolinska Institutet, 3Department of Neonatology, Karolinska University Hospital, Stockholm, SwedenBackground: Different infusion pump systems as well as gravity infusion have been widely used in neonatal transfusion. However, the limited number of published studies describing the use of infusion pumps on platelets illustrates the necessity for more robust data.Methods: To evaluate the potential in vitro effects on the cellular, metabolic, functional and phenotypic properties of platelets, we set up a four-arm paired study simultaneously comparing the use of different infusion pumps (Alaris® CC/GP with unexposed platelets. The platelet units (n=8 were either produced by the apheresis technique and suspended in 100% plasma or derived from buffy coats to yield platelet units stored in approximately 30% plasma and 70% SSP+. Fresh and 5-day old platelets were tested.Results: Regardless of the production system or storage time used, no significant differences were observed in glucose and lactate concentration, pH, adenosine triphosphate levels, response to extent of shape change, hypotonic shock response reactivity, and CD62P expression. Similarly, no differences were observed in expression of the conformational epitope on glycoprotein IIb/IIIa, determined using procaspase-activating compound 1, or in the expression of CD42b and platelet-endothelial cell adhesion molecule-1 in a comparison between platelets administered through infusion pumps versus unexposed platelets.Conclusion: Using Alaris CC/GP infusion pumps had no influence on the cellular, functional, and phenotypic in vitro properties of platelets. This fact seems not to be affected by different production systems or storage time.Keywords: platelets, neonatal platelet transfusion

  8. Reliability and validity of two frequently used self-administered physical activity questionnaires in adolescents

    Directory of Open Access Journals (Sweden)

    Kurtze Nanna

    2008-07-01

    Full Text Available Abstract Background To create and find accurate and reliable instruments for the measurement of physical activity has been a challenge in epidemiological studies. We investigated the reliability and validity of two different physical activity questionnaires in 71 adolescents aged 13–18 years; the WHO, Health Behaviour in Schoolchildren (HBSC questionnaire, and the International Physical Activity Questionnaire (IPAQ, short version. Methods The questionnaires were administered twice (8–12 days apart to measure reliability. Validity was assessed by comparing answers from the questionnaires with a cardiorespiratory fitness test (VO2peak and seven days activity monitoring with the ActiReg, an instrument measuring physical activity level (PAL and total energy expenditure (TEE. Results Intraclass correlation coefficients for reliability for the WHO HBSC questionnaire were 0.71 for frequency and 0.73 for duration. For the frequency question, there was a significant difference between genders; 0.87 for girls and 0.59 for boys (p 2peak were fair, ranging between 0.29 – 0.39. The WHO HBSC questionnaire measured against VO2peak for girls were acceptable, ranging between 0.30 – 0.55. Both questionnaires, except the walking question in IPAQ, showed a low correlation with PAL and TEE, ranging between 0.01 and 0.29. Conclusion These data indicate that the WHO HBSC questionnaire had substantial reliability and were acceptable instrument for measuring cardiorespiratory fitness, especially among girls. None of the questionnaires however seemed to be a valid instrument for measuring physical activity compared to TEE and PAL in adolescents.

  9. Effect of administering black cumin (Nigella sativa) toward postpartum mice (MusMusculus L.)

    Science.gov (United States)

    Imelda, F.; Darti, N. A.

    2018-03-01

    The period of childbirth is a period for the health provider monitoring that less monitoring can cause the mother to suffer a variety of problemsandcomplications during childbirth such as post-partum infections. This type of research was an experimental group P0: control group, treatment groups by administering Nigella sativa P1:2.6mg/day, P2:3.9mg/day, P3:5.2mg/day, and P4:6.5mg/day, which each group 5 samples. The average amount of leukocytes after given Nigella sativa 2.6mg/day for seven days (P1) which was 7:10±0:57 (x103cells/mm3), and at least in female mice after given Nigella sativa 6.5mg/day for sevendays (P4) which was 6.62±0.52 (x103cells/mm3). The average amount lymphocytes after given Nigella sativa 2.6mg/day for seven days (P1) which was 63.40±4.77 (x103cells/mm3), and least in female mice after given Nigella sativa 3.9 mg/day for seven days (P3) which was 47.00±14:58 (x103cells/mm3). Amount of monocytes after given Nigella sativa 5.2mg/day for seven days (P3) which was 5.40±0.55 (x103cells/mm3), and least in female mice after given Nigella sativa 2.6mg/day for seven days (P1) which was 4.80±1.30 (x103cells/mm3).

  10. Screening for cognitive impairment in SLE using the Self-Administered Gerocognitive Exam.

    Science.gov (United States)

    Meara, A; Davidson, N; Steigelman, H; Zhao, S; Brock, G; Jarjour, W N; Rovin, B H; Madhoun, H; Parikh, S; Hebert, L; Ayoub, I; Ardoin, S P

    2018-01-01

    Objective Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that can affect the central nervous system in multiple ways, including causing cognitive dysfunction. Cognitive dysfunction is a common complaint of SLE patients yet diagnosis is challenging, time consuming, and costly. This study evaluated the Self-Administered Gerocognitive Exam (SAGE) as a screening test for cognitive impairment in a cohort of SLE patients. Methods A total of 118 SLE patients completed the SAGE. Providers completed the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborative Clinics Damage Index (SLICC-DI). SAGE scores were grouped into normal (>16) and abnormal (≤16) categories. Univariate and multivariate analyses were performed. Results Of the 118 participants, 21(18%) scored ≤16 on the SAGE instrument. In univariate analysis, race, ethnicity, household income, and SLICC-DI scores were associated with the SAGE ( p SAGE score was independently associated with higher SLICC-DI score (odds ratio (OR) = 1.44, 95% confidence intervals 1.04-1.99, p = 0.03)), Hispanic ethnicity (OR = 43.4, 95% CI 3.1-601, p = 0.005), and lower household income (OR = 11.9 for ≤$15,000 vs >$50,000, 95% CI 2.45-57, p = 0.002). Conclusions In SLE patients, this study demonstrates an independent relationship between neurocognitive impairment (as measured by the SAGE) and higher lupus-related damage, as measured by the SLICC-DI, and lower household income. Abnormal SAGE scores were also associated with Hispanic ethnicity. A language barrier could explain this because the SAGE instrument was conducted in English only. The SAGE was feasible to measure in the clinic setting.

  11. Physiologically-based pharmacokinetic model of vaginally administered dapivirine ring and film formulations.

    Science.gov (United States)

    Kay, Katherine; Shah, Dhaval K; Rohan, Lisa; Bies, Robert

    2018-05-01

    A physiologically-based pharmacokinetic (PBPK) model of the vaginal space was developed with the aim of predicting concentrations in the vaginal and cervical space. These predictions can be used to optimize the probability of success of vaginally administered dapivirine (DPV) for HIV prevention. We focus on vaginal delivery using either a ring or film. A PBPK model describing the physiological structure of the vaginal tissue and fluid was defined mathematically and implemented in MATLAB. Literature reviews provided estimates for relevant physiological and physiochemical parameters. Drug concentration-time profiles were simulated in luminal fluids, vaginal tissue and plasma after administration of ring or film. Patient data were extracted from published clinical trials and used to test model predictions. The DPV ring simulations tested the two dosing regimens and predicted PK profiles and area under the curve of luminal fluids (29 079 and 33 067 mg h l -1 in groups A and B, respectively) and plasma (0.177 and 0.211 mg h l -1 ) closely matched those reported (within one standard deviation). While the DPV film study reported drug concentration at only one time point per patient, our simulated profiles pass through reported concentration range. HIV is a major public health issue and vaginal microbicides have the potential to provide a crucial, female-controlled option for protection. The PBPK model successfully simulated realistic representations of drug PK. It provides a reliable, inexpensive and accessible platform where potential effectiveness of new compounds and the robustness of treatment modalities for pre-exposure prophylaxis can be evaluated. © 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

  12. Piloting social engagement on a federal agency-administered Facebook page.

    Science.gov (United States)

    Chiu, Kimberly; Wagner, Lindsay; Choe, Lena; Chew, Catherine; Kremzner, Mary

    2016-01-01

    To evaluate the impact of a Federal drug information center initiating engagement with stakeholders on a Facebook Page administered by a Federal Agency. The U.S. Food and Drug Administration (FDA) Facebook page from July 21, 2014, to October 18, 2014. FDA's Division of Drug Information (DDI) in the Center for Drug Evaluation and Research (CDER) Office of Communications serves as a federal drug information center providing timely, accurate, and useful information on CDER initiatives and CDER-regulated products. We report a 90-day (July 21 to October 18, 2014) pilot during which DDI pharmacists monitored and moderated comments received on FDA's Facebook page to identify those warranting a reply. Once identified, DDI pharmacists replied within 2 business days. Impact was measured by comparing the average number of Likes, Shares, and Reach for Facebook posts before and after the pilot. Additional metrics collected include the number of DDI replies provided to stakeholders' comments and the number of DDI replies provided on time (within 2 business days). During the pilot, DDI contributed 14 posts. On average, each post reached 23,582 more individuals (an increase of 187% compared with pre-pilot posts). On average, each post also received 463 more Likes (450% increase) and 130 more Shares (271% increase). DDI pharmacists replied to 3% (121/3994) and hid 0.58% (23/3994) of Facebook comments received during the 90-day period. All actions were taken within 2 business days. Initiating social engagement had a positive impact on FDA's Facebook page. Published by Elsevier Inc.

  13. Radiosensitizing activity and pharmacokinetics of multiple dose administered KU-2285 in peripheral nerve tissue in mice

    International Nuclear Information System (INIS)

    Iwai, Hiroyuki; Matsuno, Etsuko; Sasai, Keisuke; Abe, Mitsuyuki; Shibamoto, Yuta

    1994-01-01

    In a clinical trial in which a 2-nitroimidazole radiosensitizer was administered repeatedly, the dose-limiting toxicity was found to be peripheral neuropathy. In the present study, the in vivo radiosensitizing activity of KU-2285 in combination with radiation dose fractionation, and the pharmacokinetics of cumulative dosing of KU-2285 in the peripheral nerves were examined. The ability of three nitroimidazoles, misonidazole (MISO), etanidazole (SR-2508) and KU-2285, to sensitize SCCVII tumors to radiation treatment has been compared for drug doses in the range 0-200 mg/kg. Single radiation doses or two different fractionation schedules (6 Gy/fractions x three fractions/48 h or 5 Gy/fractions x five fractions/48 h) were used; the tumor cell survival was determined using an in vivo/in vitro colony assay. The pharmacokinetics in the sciatic nerves were undertaken, when KU-2285 or etanidazole were injected at a dose of 200 mg/kg intravenously one, two, three, or four times at 2-h intervals. At less than 100 mg/kg, KU-2285 sensitized SCCVII tumors more than MISO and SR-2508 by fractionated irradiation. Evaluation of pharmacokinetics in the peripheral nerves showed that the apparent biological half-life of SR-2508 increased with the increases in the number of administrations, whereas that of KU-2285 became shorter. Since most clinical radiotherapy is given in small multiple fractions, KU-2285 appears to be a hypoxic cell radiosensitizer that could be useful in such regimens, and that poses no risk of chronic peripheral neurotoxicity. 12 refs., 5 figs., 1 tab

  14. Effects of three antagonists on selected pharmacodynamic effects of sublingually administered detomidine in the horse.

    Science.gov (United States)

    Knych, Heather K; Stanley, Scott D

    2014-01-01

    To describe the effects of alpha2 -adrenergic receptor antagonists on the pharmacodynamics of sublingual (SL) detomidine in the horse. Randomized crossover design. Nine healthy adult horses with an average age of 7.6 ± 6.5 years. Four treatment groups were studied: 1) 0.04 mg kg(-1) detomidine SL; 2) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 0.075 mg kg(-1) yohimbine intravenously (IV); 3) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 4 mg kg(-1) tolazoline IV; and 4) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 0.12 mg kg(-1) atipamezole IV. Each horse received all treatments with a minimum of 1 week between treatments. Blood samples were obtained and plasma analyzed for yohimbine, atipamezole and tolazoline concentrations by liquid chromatography-mass spectrometry. Behavioral effects, heart rate and rhythm, glucose, packed cell volume (PCV) and plasma proteins were monitored. Chin-to-ground distance increased following administration of the antagonists, however, this effect was transient, with a return to pre-reversal values as early as 1 hour. Detomidine induced bradycardia and increased incidence of atrioventricular blocks were either transiently or incompletely antagonized by all antagonists. PCV and glucose concentrations increased with tolazoline administration, and atipamezole subjectively increased urination frequency but not volume. At the doses administered in this study, the alpha2 -adrenergic antagonistic effects of tolazoline, yohimbine and atipamezole on cardiac and behavioral effects elicited by SL administration of detomidine are transient and incomplete. © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  15. Brief Video-Module Administered Mindfulness Program for Physicians: A Pilot Study.

    Science.gov (United States)

    Pflugeisen, Bethann Mangel; Drummond, Dike; Ebersole, Drew; Mundell, Kate; Chen, David

    2016-01-01

    The purpose of this study was to evaluate the feasibility of implementing a video-module-based mindfulness pilot program intended to reduce stress, improve well-being, and develop mindfulness skills in physicians in a community hospital setting. Preliminary findings are presented. Using a single-sample, pre-post study design, we administered an eight-week mindfulness training offered as part of a wellness initiative for medical staff in a suburban community hospital. Participants enrolled on a first-come, first-served basis. Participants engaged in three 90-min in-person trainings, weekly online video-module trainings, and weekly teleconference coaching calls. Video-module trainings were available at all times, to be accessed at the participants׳ convenience. Journals and a guided meditation audio library were also provided. Physician stress, well-being (emotional exhaustion, depersonalization of patients, and sense of personal accomplishment), and mindfulness skills (observing, describing, acting with awareness, and accepting without judgment) were evaluated at baseline, end-of-program, and eight weeks post-intervention using well-validated instruments. A total of 23 physicians enrolled and 19 completed the program. Compared to baseline, statistically significant decreases in stress, personal accomplishment, and emotional exhaustion were observed at end-of-program and eight weeks post-intervention (all P < .05). Significant increases in all mindfulness skills were observed at end-of-program; these increases persisted for describing, acting with awareness, and accepting without judgment at eight weeks post-intervention (all P < .05). This study provides preliminary evidence that a flexible, video-module-based mindfulness program can decrease stress, increase well-being, and develop lasting mindfulness skills in physicians. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Should unobstructed gasping be facilitated and confirmed before administering adrenaline, otherwise, give titrated vasopressin?

    Science.gov (United States)

    Rottenberg, Eric M

    2015-02-01

    A recent commentary, "Resuscitation That's (Un)Shockable: Time to Get the Adrenaline Flowing", published in the New England Journal of Medicine Journal Watch called attention to a relatively recent study showing that a large and increasing percentage of patients with in-hospital cardiac arrests exhibit initial nonshockable rhythms (asystole or pulseless electrical activity [PEA]; 82% in 2009 vs 69% in 2000) and a most recent study that concluded that neurologically intact survival to hospital discharge after in-hospital cardiac arrest was significantly more likely after earlier epinephrine administration. It was found that delayed administration of epinephrine was associated significantly with lower chance for survival to hospital discharge, in stepwise fashion (12%, 10%, 8%, and 7% survival, respectively, for patients receiving their first epinephrine dose≤3, 4-6, 7-9, and >9 minutes after arrest). Although early use of epinephrine to manage patients with nonshockable rhythms lacks strong evidence to support efficacy, focus on time to epinephrine administration-in addition to high-quality chest compressions-might be the best early intervention. However, evidence may strongly support the recommendation that adrenaline needs to be used very early because without effective-depth cardiopulmonary resuscitation (CPR) with complete recoil, epinephrine may only be effective when gasping is present, which is a time-limited phenomenon. However, because very few rescuers can perform effective-depth chest compressions with complete recoil, gasping is critically necessary for adequate ventilation and generation of adequate coronary and cerebral perfusion. However, under acidemic conditions and high catecholamine levels and/or absence of gasping, vasopressin should be administered instead. Published by Elsevier Inc.

  17. Self-administered semiquantitative food frequency questionnaires: patterns, predictors, and interpretation of omitted items

    Science.gov (United States)

    Michels, Karin B.; Willett, Walter C.

    2013-01-01

    Background Food items on a self-administered food frequency questionnaire (FFQ) may be left blank because the food was not consumed, because of difficulties remembering the frequency or amount of intake, or due to an oversight. Methods We explored the predictors and frequency of consumption of omitted food items on an FFQ used in the Nurses’ Health Study II. Of 87,676 women who returned a mailed 147-item FFQ in 1999, 34% completed the entire questionnaire, whereas 66% left at least 1 food item blank. Ten or more foods were omitted by 5% of participants. Foods were more likely omitted by women who were older, more physically active, and had more children. We resurveyed 2876 participants who had left between 1 and 70 food items blank and asked them to fill in the blanks. Overall, 2485 participants provided complete responses. Results In the resurvey, 64% of the formerly omitted foods were marked as consumed never or less than once per month, 20% as 1–3 times per month, 8% as once per week, and 9% as more than once per week. Commonly consumed foods and beverages were less likely omitted because they were not consumed than rarely consumed foods. The best estimate for the true intake value of an omitted food was 0.82 times the average population intake. Conclusions When calculating nutrient intake, the assumption that items missing represent zero intake is reasonable. However, foods consumed more often in the population at large are less likely than rarely consumed foods to be left blank because they were not consumed. PMID:19106799

  18. Acetylcholinesterase and Butyrylcholinesterase Inhibitory Compounds from Corydalis cava (Fumariaceae)

    Czech Academy of Sciences Publication Activity Database

    Chlebek, J.; Macáková, K.; Cahlíková, L.; Kurfürst, Milan; Kuneš, J.; Opletal, J.

    2011-01-01

    Roč. 6, č. 5 (2011), s. 607-610 ISSN 1934-578X Institutional research plan: CEZ:AV0Z40720504 Keywords : corydalis cava * fumariaceae * alzheimer ´s disease Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.242, year: 2011

  19. Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity

    Directory of Open Access Journals (Sweden)

    Magdalena Markowicz-Piasecka

    2017-01-01

    Full Text Available The results of epidemiological and pathophysiological studies suggest that type 2 diabetes mellitus (T2DM may predispose to Alzheimer’s disease (AD. The two conditions present similar glucose levels, insulin resistance, and biochemical etiologies such as inflammation and oxidative stress. The diabetic state also contributes to increased acetylcholinesterase (AChE activity, which is one of the factors leading to neurodegeneration in AD. The aim of this study was to assess in vitro the effects of metformin, phenformin, and metformin sulfenamide prodrugs on the activity of human AChE and butyrylcholinesterase (BuChE and establish the type of inhibition. Metformin inhibited 50% of the AChE activity at micromolar concentrations (2.35 μmol/mL, mixed type of inhibition and seemed to be selective towards AChE since it presented low anti-BuChE activity. The tested metformin prodrugs inhibited cholinesterases (ChE at nanomolar range and thus were more active than metformin or phenformin. The cyclohexyl sulfenamide prodrug demonstrated the highest activity towards both AChE (IC50 = 890 nmol/mL, noncompetitive inhibition and BuChE (IC50 = 28 nmol/mL, mixed type inhibition, while the octyl sulfenamide prodrug did not present anti-AChE activity, but exhibited mixed inhibition towards BuChE (IC50 = 184 nmol/mL. Therefore, these two bulkier prodrugs were concluded to be the most selective compounds for BuChE over AChE. In conclusion, it was demonstrated that biguanides present a novel class of inhibitors for AChE and BuChE and encourages further studies of these compounds for developing both selective and nonselective inhibitors of ChEs in the future.

  20. Silent hepatic lesions detected with computed tomography in aplastic anemia patients administered androgens for a long period

    International Nuclear Information System (INIS)

    Yamagishi, Morihisa; Hiraoka, Atsunobu; Uchino, Haruto.

    1982-01-01

    Macroscopic liver lesions were investigated with the use of computed tomography (CT) and radionuclide imaging (RN) in 15 aplastic anemia patients who were administered anabolic steroids for over one year and who showed no apparent physical and biochemical sign of liver tumor. In 3 patients, CT scans showed radiolucent areas in the liver. Contrast enhancements revealed these lesions to be well vascularized, suggesting they were not cysts but probably tumors. RN imaging could not demonstrate any definite space occupying lesions. Total dose of AS administered to each of the three patients exceeded 30,000 mg. It was felt that attention should be paid to the possible development of hepatic tumor when the dose of AS administered exceeds 30,000 mg. (author)

  1. Silent hepatic lesions detected with computed tomography in aplastic anemia patients administered androgens for a long period

    Energy Technology Data Exchange (ETDEWEB)

    Yamagishi, Morihisa (Shiga Univ., Otsu (Japan)); Hiraoka, Atsumobu; Uchino, Haruto

    1982-07-01

    Macroscopic liver lesions were investigated with the use of computed tomography (CT) and radionuclide imaging (RN) in 15 aplastic anemia patients who were administered anabolic steroids for over one year and who showed no apparent physical and biochemical sign of liver tumor. In 3 patients, CT scans showed radiolucent areas in the liver. Contrast enhancements revealed these lesions to be well vascularized, suggesting they were not cysts but probably tumors. RN imaging could not demonstrate any definite space occupying lesions. Total dose of AS administered to each of the three patients exceeded 30,000 mg. It was felt that attention should be paid to the possible development of hepatic tumor when the dose of AS administered exceeds 30,000 mg.

  2. Making instruction and assessment responsive to diverse students' progress: group-administered dynamic assessment in teaching mathematics.

    Science.gov (United States)

    Jeltova, Ida; Birney, Damian; Fredine, Nancy; Jarvin, Linda; Sternberg, Robert J; Grigorenko, Elena L

    2011-01-01

    This study entailed a 3 (instructional intervention) × 2 (assessment-type) between-subjects experimental design employing a pretest-intervention-posttest methodology. The instructional interventions were administered between subjects in three conditions: (a) dynamic instruction, (b) triarchic or theory of successful intelligence-control instruction, and (c) standard-control instruction. The assessment-type consisted between subjects of either (a) a group-administered dynamic posttest or (b) the same group-administered posttest interspersed with a control filler activity. Performance in different mathematics content areas taught in fourth grade was investigated. In total, 1,332 students and 63 classroom teachers in 24 schools across six school districts participated in the study. The results indicate the advantages of using dynamic instruction and assessment in regular classrooms while teaching mathematics, especially when the student body is highly ethnically diverse.

  3. Dose estimation and radiation control measures for individuals having close contact with patients administered in vivo nuclear medicine

    International Nuclear Information System (INIS)

    Konishi, E.; Abe, K.; Kusama, T.

    1993-01-01

    Patients who have been administered radiopharmaceuticals become a source of exposure to a non-occupational individual helping in support and comfort of these patients. We measured external dose rates at several distances from 84 adult patients administered radiopharmaceuticals, and urinary excretion of radioactivity in their patients. And we estimated the maximal dose for persons having close contact with patients administered radiopharmaceuticals from the combination of these measurement data and scenarios of contact with patients. On the basis of the estimated values, we proposed the following dose constraint for care givers. (1) The dose constraint for a non-occupational care givers to an adult nuclear medicine patient should in no case exceed 300 μSv per patient per examination of any kind. (2) The dose constraint in ordinary examinations employing a radionuclide should not be greater than 15 μSv per patient per examination. (3 tabs.)

  4. [Targeting the brain through the nose. Effects of intranasally administered insulin].

    Science.gov (United States)

    Brünner, Y F; Benedict, C; Freiherr, J

    2013-08-01

    The assumption that the human brain is an insulin-independent organ was disproved with the discovery of insulin receptors in the central nervous system in the year 1978. Evidence has been provided for a high density of insulin receptors in brain regions responsible for cognitive memory processes (hippocampus) and for the regulation of appetite (hypothalamus). Accordingly, in animal studies an increased insulin level in the central nervous system leads to an improvement of hippocampal memory function and a decrease of food intake. Similar results were obtained in humans using the method of intranasal administration of insulin. Intranasal insulin reaches the brain and the cerebrospinal fluid via the olfactory epithelium and olfactory nerve fiber bundles leading through the lamina cribrosa to the olfactory bulb. Thus, this method renders the investigation of specific insulin effects in humans possible. The therapeutic potential of an intranasal insulin administration for the treatment of diseases for which an imbalance of the central nervous insulin metabolism is discussed (e.g. Alzheimer's disease, diabetes mellitus and obesity) can only be estimated with the help of further clinical studies.

  5. Telephone-administered psychotherapy in combination with antidepressant medication for the acute treatment of major depressive disorder.

    Science.gov (United States)

    Corruble, Emmanuelle; Swartz, Holly A; Bottai, Thierry; Vaiva, Guillaume; Bayle, Frank; Llorca, Pierre-Michel; Courtet, Philippe; Frank, Ellen; Gorwood, Philip

    2016-01-15

    Telephone-administered psychotherapies (T-P) provided as an adjunct to antidepressant medication may improve response rates in major depressive disorder (MDD). The goal of this study was to compare telephone-administered social rhythm therapy (T-SRT) and telephone-administered intensive clinical management (T-ICM) as adjuncts to antidepressant medication for MDD. A secondary goal was to compare T-P with Treatment as Usual (TAU) as adjunctive treatment to medication for MDD. 221 adult out-patients with MDD, currently depressed, were randomly assigned to 8 sessions of weekly T-SRT (n=110) or T-ICM (n=111), administered as an adjunct to agomelatine. Both psychotherapies were administered entirely by telephone, by trained psychologists who were blind to other aspects of treatment. The 221 patients were a posteriori matched with 221 depressed outpatients receiving TAU (controls). The primary outcome measure was the percentage of responders at 8 weeks post-treatment. No significant differences were found between T-SRT and T-ICM. But T-P was associated with higher response rates (65.4% vs 54.8%, p=0.02) and a trend toward higher remission rates (33.2% vs 25.1%; p=0.06) compared to TAU. Short term study. This study is the first assessing the short-term effects of an add-on, brief, telephone-administered psychotherapy in depressed patients treated with antidepressant medication. Eight sessions of weekly telephone-delivered psychotherapy as an adjunct to antidepressant medication resulted in improved response rates relative to medication alone. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Nasally-Administered Oxytocin Has Limited Effects on Owner-Directed Attachment Behavior in Pet Dogs (Canis lupus familiaris

    Directory of Open Access Journals (Sweden)

    Lauren E. Thielke

    2017-09-01

    Full Text Available The present study explored the effects of intranasal oxytocin, a naturally occurring hormone, on the behavior of pet dogs during an attachment test. Each dog participated in two testing sessions. On one visit saline was administered nasally, and on another, oxytocin was administered nasally. For half of the dogs (n = 20, solutions were administered with a Mucosal Atomization Device (MAD and for half of the dogs (n = 20, solutions were administered using a nasal spray bottle. Condition order was counterbalanced and a double-blind methodology was employed. Following a 30-min wait period after administration of solutions, dog-owner pairs participated in the Secure Base Test, a short attachment test consisting of three 2-min phases: (1 Baseline- the owner was present, dogs were able to freely explore the testing room (2 Alone- dogs were left alone in the testing room (3 Return- owners re-entered the room and were reunited with their dog. In each phase the dog was evaluated for contact seeking, exploration, and avoidance behaviors. Although, oxytocin administration was expected to increase owner-directed proximity and contact seeking behavior, this effect was not observed. In fact, in the baseline phase, dogs spent significantly more time seeking the proximity of their owners when they received saline than when they received OT (p < 0.05. Sex differences were also assessed for the behavioral variables of interest in the Secure Base Test, and results indicated that OT did not affect dogs' behavior in the alone phase, but when saline was administered, females spent significantly more time in contact with the door than males in the alone phase (p < 0.05. Overall, the effects of nasally administered oxytocin on attachment related behavior appeared to be limited or inconsistent for this pet dog population.

  7. Tabhu: tools for antibody humanization

    DEFF Research Database (Denmark)

    Olimpieri, Pier Paolo; Marcatili, Paolo; Tramontano, Anna

    2015-01-01

    Antibodies are rapidly becoming essential tools in the clinical practice, given their ability to recognize their cognate antigens with high specificity and affinity, and a high yield at reasonable costs in model animals. Unfortunately, when administered to human patients, xenogeneic antibodies can...... elicit unwanted and dangerous immunogenic responses. Antibody humanization methods are designed to produce molecules with a better safety profile still maintaining their ability to bind the antigen. This can be accomplished by grafting the non-human regions determining the antigen specificity...... and time-consuming experiments. Here we present tools for antibody humanization (Tabhu) a web server for antibody humanization. Tabhu includes tools for human template selection, grafting, back-mutation evaluation, antibody modelling and structural analysis, helping the user in all the critical steps...

  8. Analysis of Kras gene from induced pancreatic cancer rats administered with Momordicacharantia and Ocimumbasilicum leaf extracts

    Directory of Open Access Journals (Sweden)

    J.B. Minari

    2018-04-01

    Full Text Available Objective: To analyze K-ras gene from induced pancreatic cancer rats administered with Momordicacharantia and Ocimumbasilicum leaf extracts. Methods: Twenty-five (25 adult rats weighing between 90–120 g were divided into 5 groups namely RA, RB, RC, NC and PC, each group had 5 rats. The PC which served as the control was fed with normal fish meal and water ad libitum; the NC which is the negative control received 20 mg/ml/week of Nitrosamines only while other groups received different concentrations of aqueous extract of both M. charantia and O. basilicum (200 mg, 100 mg, 50 mg and Nitrosamine. Qualitative phytochemical screening of the aqueous extract of both M. charantia and O. basilicum was carried out. The extraction of DNA was done using Jena Bioscience DNA preparation kit and the protocol was based on the spin column based genomic DNA purification from blood, animal and plant cells. Agarose gel electrophoresis was used to analyze the K-ras gene extracted from the pancreas tissues of experimental rats while hematoxylinand eosin staining was used for histological assay. Results: Phytochemical screening revealed the presence of alkaloids, tannins, flavonoids, saponins and glycosides in M. charantia while saponins, tannins and glycosides were discovered in O. basilicum. Significant reduction in the weight of rats treated with 200 mg of aqueous extracts of M. charantia and O. basilicum while rats that were dosed with nitrosamines only showed a slight increase in weight in the first three weeks when compared to the positive control. Histological studies revealed that there is both enlargement and reduction in the islet cell size, with one of the sections showing a normal islet cell size. While the agarose gel electrophoresis revealed that there may be possibility of prevention of damage to k-ras gene as a result of the effect of plants extract. Conclusion: This work has shown that the leaf extracts of both M. charantia and O. basilicum

  9. Effects of chelating agent CBMIDA on the toxicity of depleted uranium administered subcutaneously in rats

    International Nuclear Information System (INIS)

    Fukuda, Satoshi; Ikeda, Mizuyo; Nakamaura, Mariko

    2008-01-01

    We examined the acute toxicity of depleted uranium (DU) after subcutaneous injection as a simulated wounds model, and the effects of the chelating agent catechol-3,6-bis(methyliminodiacetic acid) (CBMIDA), by local treatment in rats. First, to examine the initial behavior and toxicity of uranium of different chemical forms, male Wistar rats were subcutaneously injected with 4 and 16 mg/kg DU (pH 1) in a solution of pH 1 and 7, respectively, and were killed 1, 3, 6 and 24 hours later. After the injection of DU(pH1), about 60% of the uranium was retained for first 1-3 hours at the injected sites, and then decreased to 16% at 24 hours in the 4 mg/kg DU group; however, the uranium did not change significantly in the 16 mg/kg DU group. Urinary excretion rates of uranium increased in a time-independent manner after the injection Depositions of uranium in the liver, kidneys and femur were found at 1 hour after DU injection, with significant increases in serum and urinary biochemical markers indicating acute and severe damage. The results of the DU (pH 7) injection were useful for estimating the toxicity of uranium by the chemical changes in the body. Second, CBMIDA (480 mg/kg) was infused into the DU-injected site at 0, 10, 30, 60 min and 24 hours after the subcutaneous injection of 4 mg/kg DU (pH 1 and 7). When CBMIDA was administered within 120 min after DU (pH 1) injection, the uranium at the injected sites decreased to 4-17% of that in the no-treatment DU (pH 1) group, and was excreted effectively in the urine and feces, with decreased levels in the kidneys and femur. The results indicated that the subcutaneously injected uranium acutely induced severe damage in the DU-injected sites and organs after DU intake, relating to chemical forms of uranium by pH and that local treatment of CBMIDA was effective in decreasing the acute toxicity of uranium if carried out as early as possible (at least within 2 hours) after DU administration. (author)

  10. Response of shortgrass Plains vegetation to chronic and seasonally administered gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Fraley, Jr., Leslie [Colorado State Univ., Fort Collins, CO (United States)

    1971-08-01

    In order to determine the effect of radiation on the structure of native shortgrass plains vegetation, an 8750 Ci 137Cs source was installed on the Central Plains Experimental Range near Nunn, Colorado; The experimental area was divided into 6 treatment sectors, a control, 2 sectors for chronic exposure (irradiation initiated April 1969 and continuing as of August 1971), and one each for spring, summer and late fall seasonal semi-acute (30 day), exposures which were administered during April, July and December, 1969, respectively. Community structure was measured by coefficient of community and diversity index. Yield was determined by clipping plots in September 1970 and visual estimates in September 1969 and 1970 for the grass-sedge component of the vegetation. Individual species sensitivity was determined by density data recorded in April, June and September of 1969 and 1970 and by a phenological index recorded at weekly intervals during the 1969 and 1970 growing seasons. The response of the vegetation was similar whether determined by coefficient of community or diversity with diversity being a more sensitive measure of effects. In the chronically exposed sectors, the exposure rate which resulted in a 50 per cent reduction in these 2 parameters (CC50 or D50) was still decreasing the second growing season and was approximately 18 R/hr for the CC50 as of June 1970 and 10 R/hr for the D50 as of September 1970. For the seasonally exposed sectors, the late fall period (December, 1969) was the most sensitive, summer (July, 1969) the least sensitive and spring (April, 1969) intermediate with CC50 and D50 values of 195 and 90, 240 and 222, and 120 and 74 R/hr for the spring, summer and late fall exposed sectors, respectively. Yield and density data indicated a rapid revegetation of the spring and summer exposed sectors during 1970 as a result of an influx of invader species such as Salsola kali tenuifolia, Chenopodium leptophyllum and Lepidium densiflorum and the

  11. Gold nanoparticles and diclofenac diethylammonium administered by iontophoresis reduce inflammatory cytokines expression in Achilles tendinitis

    Directory of Open Access Journals (Sweden)

    Dohnert MB

    2012-03-01

    Full Text Available Marcelo B Dohnert1,2, Mirelli Venâncio1, Jonathann C Possato1, Rodrigo C Zeferino1, Luciana H Dohnert2, Alexandra I Zugno1, Cláudio T De Souza1, Marcos MS Paula1, Thais F Luciano11Postgraduation Program in Health Sciences, Programa de Pós-graduação em Ciências da Saúde PPGCS, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina, 2Department of Physiotherapy, Universidade Luterana do Brasil, Torres, Rio Grande do Sul, BrazilIntroduction: Tendinitis affects a substantial number of people in several occupations involving repetitive work or direct trauma. Iontophoresis is a therapeutic alternative used in the treatment of injury during the inflammatory phase. In recent years, gold nanoparticles (GNP have been studied due to their therapeutic anti-inflammatory capacity and as an alternative to the transport of several proteins. Purpose: This study evaluates the therapeutic effects of iontophoresis using GNPs and diclofenac diethylammonium on inflammatory parameters in rats challenged with traumatic tendinitis.Methods: Wistar rats were divided in three treatment groups (n = 15: (1 iontophoresis + diclofenac diethylammonium; (2 iontophoresis + GNP; and (3 iontophoresis + diclofenac diethylammonium + GNP. External control was formed by challenged tendons without treatment (n = 15. Iontophoresis was administered using 0.3 mA direct current on 1.5 cm² electrodes. Results: The levels of both inflammatory cytokines were significantly higher in untreated challenged rats, when compared with the control (5.398 ± 234 for interleukin 1 beta and 6.411 ± 432 for tumor necrosis factor alpha, which confirms the occurrence of an inflammatory stage in injury (P < 0.05. A significant decrease was observed in expression of cytokines interleukin 1 beta in the three treatment groups, in comparison with untreated challenged tendons, although, in the group treated with diclofenac and GNP, results were similar to the control (1.732 ± 239 (P < 0

  12. Systemic and Mucosal Antibody Responses to Soluble and Nanoparticle-Conjugated Antigens Administered Intranasally

    Directory of Open Access Journals (Sweden)

    Savannah E. Howe

    2016-10-01

    Full Text Available Nanoparticles (NPs are increasingly being used for drug delivery, as well as antigen carriers and immunostimulants for the purpose of developing vaccines. In this work, we examined how intranasal (i.n. priming followed by i.n. or subcutaneous (s.c. boosting immunization affects the humoral immune response to chicken ovalbumin (Ova and Ova conjugated to 20 nm NPs (NP-Ova. We show that i.n. priming with 20 mg of soluble Ova, a dose known to trigger oral tolerance when administered via gastric gavage, induced substantial systemic IgG1 and IgG2c, as well as mucosal antibodies. These responses were further boosted following a s.c. immunization with Ova and complete Freund’s adjuvant (Ova+CFA. In contrast, 100 µg of Ova delivered via NPs induced an IgG1-dominated systemic response, and primed the intestinal mucosa for secretion of IgA. Following a secondary s.c. or i.n. immunization with Ova+CFA or NP-Ova, systemic IgG1 titers significantly increased, and serum IgG2c and intestinal antibodies were induced in mice primed nasally with NP-Ova. Only Ova- and NP-Ova-primed mice that were s.c.-boosted exhibited substantial systemic and mucosal titers for up to 6 months after priming, whereas the antibodies of i.n.-boosted mice declined over time. Our results indicate that although the amount of Ova delivered by NPs was 1000-fold less than Ova delivered in soluble form, the antigen-specific antibody responses, both systemic and mucosal, are essentially identical by 6 months following the initial priming immunization. Additionally, both i.n.- and s.c.-boosting strategies for NP-Ova-primed mice were capable of inducing a polarized Th1/Th2 immune response, as well as intestinal antibodies; however, it is only by using a heterogeneous prime-boost strategy that long-lasting antibody responses were initiated. These results provide valuable insight for future mucosal vaccine development, as well as furthering our understanding of mucosal antibody responses.

  13. Distribution and histologic effects of intravenously administered amorphous nanosilica particles in the testes of mice

    International Nuclear Information System (INIS)

    Morishita, Yuki; Yoshioka, Yasuo; Satoh, Hiroyoshi; Nojiri, Nao; Nagano, Kazuya; Abe, Yasuhiro; Kamada, Haruhiko; Tsunoda, Shin-ichi; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Tsutsumi, Yasuo

    2012-01-01

    Highlights: ► There is rising concern regarding the potential health risks of nanomaterials. ► Few studies have investigated the effect of nanomaterials on the reproductive system. ► Here, we evaluated the intra-testicular distribution of nanosilica particles. ► We showed that nanosilica particles can penetrate the blood-testis barrier. ► These data provide basic information on ways to create safer nanomaterials. -- Abstract: Amorphous nanosilica particles (nSP) are being utilized in an increasing number of applications such as medicine, cosmetics, and foods. The reduction of the particle size to the nanoscale not only provides benefits to diverse scientific fields but also poses potential risks. Several reports have described the in vivo and in vitro toxicity of nSP, but few studies have examined their effects on the male reproductive system. The aim of this study was to evaluate the testicular distribution and histologic effects of systemically administered nSP. Mice were injected intravenously with nSP with diameters of 70 nm (nSP70) or conventional microsilica particles with diameters of 300 nm (nSP300) on two consecutive days. The intratesticular distribution of these particles 24 h after the second injection was analyzed by transmission electron microscopy. nSP70 were detected within sertoli cells and spermatocytes, including in the nuclei of spermatocytes. No nSP300 were observed in the testis. Next, mice were injected intravenously with 0.4 or 0.8 mg nSP70 every other day for a total of four administrations. Testes were harvested 48 h and 1 week after the last injection and stained with hematoxylin–eosin for histologic analysis. Histologic findings in the testes of nSP70-treated mice did not differ from those of control mice. Taken together, our results suggest that nSP70 can penetrate the blood-testis barrier and the nuclear membranes of spermatocytes without producing apparent testicular injury.

  14. Preliminary investigation of orally administered benazepril in horses with left-sided valvular regurgitation.

    Science.gov (United States)

    Afonso, T; Giguère, S; Brown, S A; Barton, M H; Rapoport, G; Barba, M; Dembek, K A; Toribio, R E; Coleman, A E

    2017-10-17

    Despite the paucity of data available, orally administered angiotensin-converting enzyme (ACE) inhibitors are empirically used in horses with valvular regurgitation. Evaluate the echocardiographic and hormonal changes in response to oral benazepril in horses with left-sided valvular regurgitation. Prospective, randomised double-blind, placebo-controlled trial. Horses with mitral valve (MR) and/or aortic valve regurgitation (AR) received oral benazepril (n = 6) at a dosage of 1 mg/kg q 12 h or a placebo (n = 5) for 28 days. Echocardiography was performed before drug administration and after 28 days of treatment. Plasma renin activity, serum ACE activity, angiotensin II concentration, aldosterone concentration and biochemical variables were measured before drug administration and after 7 and 28 days of treatment. Relative to baseline, horses treated with benazepril had statistically significant reduction in left ventricular internal diameter in systole (mean difference between groups = -0.97 cm; 95% CI = -1.5 to -0.43 cm), aortic sinus diameter (-0.31 cm; -0.54 to -0.07 cm), and percentage of the aortic annulus diameter occupied by the base of the AR jet (-17.05%; -31.17 to -2.93%) compared with horses receiving a placebo. In addition, horses treated with benazepril had a significantly greater increase in cardiac output (11.95 L/min; 1.17-22.73 L/min) and fractional shortening (7.59%; 3.3-11.88%) compared with horses receiving a placebo. Despite profound serum ACE inhibition, renin activity and concentrations of angiotensin II and aldosterone were not significantly different between treatment groups or among time points. Very small sample size and short treatment period. Treatment with oral benazepril resulted in statistically significant echocardiographic changes that might indicate reduced cardiac afterload in horses with left-sided valvular regurgitation. Additional studies with a larger sample size will be necessary to determine if administration of benazepril is

  15. Distribution and histologic effects of intravenously administered amorphous nanosilica particles in the testes of mice

    Energy Technology Data Exchange (ETDEWEB)

    Morishita, Yuki [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Yoshioka, Yasuo, E-mail: yasuo@phs.osaka-u.ac.jp [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Satoh, Hiroyoshi; Nojiri, Nao [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Nagano, Kazuya [Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085 (Japan); Abe, Yasuhiro [Cancer Biology Research Center, Sanford Research/USD, 2301 E. 60th Street N, Sioux Falls, SD 57104 (United States); Kamada, Haruhiko; Tsunoda, Shin-ichi [Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Nabeshi, Hiromi [Division of Foods, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo 158-8501 (Japan); Yoshikawa, Tomoaki [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tsutsumi, Yasuo, E-mail: ytsutsumi@phs.osaka-u.ac.jp [Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Laboratory of Biopharmaceutical Research, National Institute of Biomedical Innovation, 7-6-8 Saitoasagi, Ibaraki, Osaka 567-0085 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan)

    2012-04-06

    Highlights: Black-Right-Pointing-Pointer There is rising concern regarding the potential health risks of nanomaterials. Black-Right-Pointing-Pointer Few studies have investigated the effect of nanomaterials on the reproductive system. Black-Right-Pointing-Pointer Here, we evaluated the intra-testicular distribution of nanosilica particles. Black-Right-Pointing-Pointer We showed that nanosilica particles can penetrate the blood-testis barrier. Black-Right-Pointing-Pointer These data provide basic information on ways to create safer nanomaterials. -- Abstract: Amorphous nanosilica particles (nSP) are being utilized in an increasing number of applications such as medicine, cosmetics, and foods. The reduction of the particle size to the nanoscale not only provides benefits to diverse scientific fields but also poses potential risks. Several reports have described the in vivo and in vitro toxicity of nSP, but few studies have examined their effects on the male reproductive system. The aim of this study was to evaluate the testicular distribution and histologic effects of systemically administered nSP. Mice were injected intravenously with nSP with diameters of 70 nm (nSP70) or conventional microsilica particles with diameters of 300 nm (nSP300) on two consecutive days. The intratesticular distribution of these particles 24 h after the second injection was analyzed by transmission electron microscopy. nSP70 were detected within sertoli cells and spermatocytes, including in the nuclei of spermatocytes. No nSP300 were observed in the testis. Next, mice were injected intravenously with 0.4 or 0.8 mg nSP70 every other day for a total of four administrations. Testes were harvested 48 h and 1 week after the last injection and stained with hematoxylin-eosin for histologic analysis. Histologic findings in the testes of nSP70-treated mice did not differ from those of control mice. Taken together, our results suggest that nSP70 can penetrate the blood-testis barrier and the

  16. The emergence and maintenance of vector-borne diseases in the Khyber Pakhtunkhwa Province (KPK and the Federally Administered Tribal Areas (FATA of Pakistan

    Directory of Open Access Journals (Sweden)

    Nathan Christopher Nieto

    2012-07-01

    Full Text Available Human populations throughout much of the world are experiencing unprecedented changes in their relationship to the environment and their interactions with the animals with which so many humans are intimately dependent upon. These changes result not only from human induced changes in the climate, but also from population demographic changes due to wars, social unrest, behavioral changes resulting from cultural mixing, and large changes in land-use practices. Each of these social shifts can affect the maintenance and emergence of arthropod vectors disease or the pathogenic organisms themselves. A good example is the country of Pakistan, with a large rural population and developing urban economy, it also maintains a wide diversity of entomological disease vectors, including biting flies, mosquitoes, and ticks. Pathogens endemic to the region include the agents of piroplasmosis, rickettsiosis, spirocheteosis, and viral hemorrhagic fevers and encephalitis. The northwestern region of the country, including the Khyber Pakhtunkhwa Province (KPK, formerly the North-West Frontier Provence (NWFP, and the Federally Administered Tribal Areas (FATA are mountainous regions with a high degree of habitat diversity that has recently undergone a massive increase in human population density due to an immigrating refugee population from neighboring war-torn Afghanistan. Vector-borne diseases in people and livestock are common in KPK and FATA regions due to the limited use of vector control measures and access to livestock vaccines. The vast majority of people in this region live in abject poverty with >70% of the population living directly from production gained in animal husbandry. In many instances whole families live directly alongside their animal counterparts. In addition, there is little to no awareness of the threat posed by ticks and transmission of either zoonotic or veterinary pathogens. Recent emergence of Crimean-Congo hemorrhagic fever virus in rural

  17. 20 CFR 408.1205 - How can a State have SSA administer its State recognition payment program?

    Science.gov (United States)

    2010-04-01

    ... recognition payment program? 408.1205 Section 408.1205 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SPECIAL BENEFITS FOR CERTAIN WORLD WAR II VETERANS Federal Administration of State Recognition Payments § 408.1205 How can a State have SSA administer its State recognition payment program? A State (or...

  18. 38 CFR 2.3 - Delegation of authority to employees to take affidavits, to administer oaths, etc.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Delegation of authority to employees to take affidavits, to administer oaths, etc. 2.3 Section 2.3 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS DELEGATIONS OF AUTHORITY § 2.3 Delegation of authority to...

  19. 12 CFR 361.5 - What are the FDIC's oversight and monitoring responsibilities in administering this program?

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false What are the FDIC's oversight and monitoring responsibilities in administering this program? 361.5 Section 361.5 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY MINORITY AND WOMEN OUTREACH PROGRAM CONTRACTING § 361...

  20. 7 CFR 1.29 - Subpoenas relating to investigations under statutes administered by the Secretary of Agriculture.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Subpoenas relating to investigations under statutes administered by the Secretary of Agriculture. 1.29 Section 1.29 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Departmental Proceedings § 1.29 Subpoenas relating to investigations...